HK1113655A - Imine compound - Google Patents

Description

Imine compound

Technical Field

The present invention relates to imine compounds having cannabinoid (cannabinoid) receptor agonistic action (agonistic action).

Background

Cannabinoids are isolated as physiologically active components of cannabis in 1960, and have analgesic, anxiolytic, sedative, and euphoric effects. Then, by finding out the receptor, an endogenous ligand having cannabinoidal-like physiological activity, such as anandamide (anandamide), was found.

Cannabinoid receptor type 1 (CB1) receptor was discovered in 1990 as a cannabinoid receptor, and is known to be distributed in the central nervous system such as the brain, and agonists thereof have been shown to exhibit analgesic effects. Cannabinoid type 2 (CB2) receptors were discovered in 1993 and are known to be distributed in tissues or cells of the immune system including spleen, lymph nodes, and blood cell lines such as leukocytes, B cells, T cells, macrophages, and mast cells, and agonists thereof have been shown to have immunosuppressive, anti-inflammatory, and analgesic effects.

Examples of compounds having CB1 receptor agonistic action and compounds having CB2 receptor agonistic action are disclosed in non-patent documents 1 and 2.

The imine compounds having a structure similar to that of the compound of the present invention are described in, for example, non-patent documents 3 to 8 and patent documents 1 to 20. As the use thereof, various uses such as agricultural fungicides, herbicides, platelet aggregation inhibitors, therapeutic agents for various inflammations caused by leukocyte infiltration inhibition, antiallergic agents, antiinflammatory agents, immunomodulators, analgesics, and the like have been reported. However, no cannabinoid receptor agonistic action has been reported which contains an imine compound as an active ingredient.

Non-patent document 1, exp. opin. the patent (2002)12 (10): 1475-1489

Non-patent document 2, exp. opin. the same. patent (2004)14 (10): 1435-1452

[ non-patent document 3] European Journal of Medicinal chemistry (1994)29 (11): 841-854

[ non-patent document 4] Journal of Medicinal chemistry (1966)9 (1): 151-153

[ non-patent document 5] IzVestiya Akademiii Nauk SSSR, Seriya Kimicheskaya (1953): 154-162

[ Nonpatent document 6 ] Farmaco, Edizone scientific (1985)40 (3): 178-189

[ non-patent document 7 ] Journal of Heterocyclic Chemistry (1983)20 (5): 1153-1154

[ non-patent document 8 ] Journal of Heterocyclic Chemistry (1981)18 (4): 745-750

[ patent document 1] WO9215564

[ patent document 2 ] EP432600

[ patent document 3] DE1036326

[ patent document 4] WO2001055139

[ patent document 5] WO2000063207

[ patent document 6 ] JP2003292485

[ patent document 7 ] WO2002002542

[ patent document 8 ] WO2003097605

[ patent document 9 ] JP2003192591

[ patent document 10 ] WO2000017196

WO9842703 (patent document 11)

[ patent document 12 ] WO2002002542

[ patent document 13 ] JP02250874

[ patent document 14 ] JP62004277

[ patent document 15 ] EP40573

[ patent document 16 ] JP63203672

[ patent document 17 ] JP08081449

[ patent document 18 ] WO9703058

WO9404516 [ patent document 19 ]

[ patent document 20 ] JP02229164

Disclosure of Invention

The object of the present invention is to provide a novel imine compound having a cannabinoid receptor agonistic action.

The present inventors have conducted intensive studies on imine compounds and as a result, have found a novel imine compound having a cannabinoid receptor agonistic action, thereby completing the present invention.

The present invention will be described below.

The present invention provides a cannabinoid receptor agonist comprising an imine compound represented by the formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient.

[ CHEM 1]

[ wherein A represents any ring represented by the following formulae (wherein X represents an oxygen atom or a sulfur atom, and X' represents a CH or a nitrogen atom),

[ CHEM 2 ]

R¹To represent

A hydrogen atom;

a halogen atom;

c which may be substituted by "aryl substituted by halogen atom_1-10An alkyl group;

C_3-10a cycloalkyl group;

C_2-6an alkenyl group;

C_1-6a haloalkyl group;

C_1-10an alkoxy group;

a carboxyl group;

C_2-6an alkoxycarbonyl group;

hydroxy radical C_1-6An alkyl group;

formula-N (R)⁶)R⁷(in the formula, R⁶And R⁷Each represents a hydrogen atom or C_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom);

formula-CON (R)⁶¹)R⁷¹(in the formula, R⁶¹And R⁷¹Each represents a hydrogen atom or C which may be substituted by a cyclic amino group_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom); or

Can be selected from C_1-6Alkyl radical, C_1-6Aryl substituted with 1 to 3 groups of a halogenated alkyl group and a halogen atom,

R²and R³Respectively represent

A hydrogen atom;

a halogen atom;

C_1-6an alkyl group;

C_1-6a haloalkyl group; or

Can be selected from C_1-6Alkyl radical, C_1-6Aryl substituted with 1 to 3 groups of a halogenated alkyl group and a halogen atom,

R⁴to represent

C_1-10An alkyl group;

C_1-6a haloalkyl group;

quilt C_3-10Cycloalkyl radical, C_1-6Alkoxy, hydroxy, amino, phthalimido, cyano, arylthio, C_2-6Alkoxycarbonyl, carboxyl, formula-CON (R)⁶²)R⁷²(in the formula, R⁶²And R⁷²Each represents a hydrogen atom or C_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom), or may be represented by "C_1-6Haloalkyl, C_2-6Alkoxycarbonyl, carboxy or N-piperidinocarbonyl "substituted aryl substituted C_1-10Alkyl or C_2-6An alkenyl group;

C_2-6a haloalkenyl group;

C_2-6an alkynyl group;

1, 1-dioxotetrahydrothienyl;

or an aryl group, or a salt thereof,

R⁵to represent

A hydrogen atom;

C_1-10an alkoxy group;

C_1-6alkoxy radical C_1-6An alkoxy group;

C_1-6a haloalkyl group;

may be selected from halogen atoms, C_3-10Cycloalkyl radical, C_2-6Alkoxycarbonyl group, C_1-6Haloalkyl, optionally substituted by "C_1-6Alkoxy or aryl "substituted C_1-6Alkoxy, optionally substituted by 1 to 2C_1-6Alkyl substituted C_3-10Cycloalkoxy, which may be selected from "C_1-6Alkyl radical, C_1-6Alkoxy radical, C_1-6Haloalkyl, C_1-6Aryl or aryloxy substituted with 1 to 5 groups of haloalkoxy, aralkyloxy, nitro and halogen atoms', heterocyclic group, phthalimido group, C_1-6Alkanoyloxy, aralkyloxy, C_1-6Alkylthio, arylthio and-N (R)⁶²)R⁷²(in the formula, R⁶²And R⁷²Each represents a hydrogen atom or C_1-6Alkyl or a group which forms a cyclic amino group together with an adjacent nitrogen atom) and C substituted with 1 to 3 groups_1-10Alkyl or C_2-6An alkenyl group;

can be covered with C_1-6Alkyl radical, C_1-6Alkoxy radical, C_2-6Alkoxycarbonyl group, C_1-6Haloalkyl or C_1-6Haloalkoxy-substituted aryloxy;

an aralkyloxy group;

a group represented by the formula (II),

[ CHEM 3]

{ wherein, B represents

C_3-10A cycloalkyl group;

an aryl group;

a heterocyclic group;

C_2-6a cyclic amino group;

a fluorenyl group;

a phthalimido group;

2-oxopyrrolidinyl;

a group represented by the formula (III);

[ CHEM 4]

(wherein n represents 0 or 1.)

Or a group represented by formula (IV);

[ CHEM 5]

(wherein Y represents- (CH)₂)p-、-CO-CH₂-CH₂-、-CO-CH₂-CH₂-CH₂-、-O-CH₂-CH₂-、-O-CH₂-CH ═ CH-or-O- (CH)₂) q-O-, p represents an integer of 2 to 4, q represents an integer of 1 to 3)

R⁵⁵To represent

A hydrogen atom;

a halogen atom;

can be: aryl, heterocyclic or aryloxy groups which may be substituted by halogen atoms, or of the formula-N (R)⁶²)R⁷²(in the formula, R⁶²And R⁷²Each represents a hydrogen atom or C_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom) or a pharmaceutically acceptable salt thereof_1-10An alkyl group;

C_1-6a haloalkyl group;

C_1-10an alkoxy group;

C_1-6an alkylthio group;

C_1-6an alkylsulfonyl group;

can be covered with C_1-6Alkyl or halogenAn atom-substituted arylsulfonyl group;

C_1-6a haloalkoxy group;

C_1-6a haloalkylthio group;

C_3-10a cycloalkyl group;

C_2-6an alkenyl group;

C_2-6an alkenyloxy group;

C_2-6an alkenylthio group;

C_1-6alkoxy radical C_1-6An alkoxy group;

can be selected from C_1-6Alkyl radical, C_1-6Haloalkyl group, halogen atom, C_1-6Aryl substituted with 1 to 3 groups of alkoxy, cyano and nitro;

can be covered with C_1-6Alkyl or C_1-6A haloalkyl substituted heterocyclic group;

may be substituted by halogen atoms or C_1-6An alkyl-substituted aryloxy or arylthio group;

formula-N (R)⁶³)R⁷³(in the formula, R⁶³And R⁷³Each represents a hydrogen atom, C_1-6Alkyl radical, C_1-6Hydroxyalkyl radical, C_1-6Alkoxy radical C_1-6Alkyl, aryl, C_1-6Alkanoyl, di-C_1-6Alkylamino radical C_2-6Alkanoyl, benzoyl or can be substituted by C_1-6An alkyl-substituted heterocyclic group, or a group which represents a cyclic amino group bonded together with an adjacent nitrogen atom);

a hydroxyl group;

a cyano group;

a nitro group;

C_1-6an alkanoyl group;

C_1-6an alkanoyloxy group;

C_1-6alkanoyloxy group C_1-6An alkyl group;

C_2-6a haloalkanoyl group;

a carboxyl group;

C_2-6an alkoxycarbonyl group;

c which may be substituted by aryl_2-6A cyclic amino group;

formula-CON (R)⁶⁴)R⁷⁴(in the formula, R⁶⁴And R⁷⁴Each represents a hydrogen atom, C_1-6Alkyl radical, C_1-6Alkoxy radical C_1-6Alkyl, or may be substituted by C_1-6An alkyl-substituted heterocyclic group, or a group which represents a cyclic amino group bonded together with an adjacent nitrogen atom);

formula-SO₂N(R⁶²)R⁷²(in the formula, R⁶²And R⁷²Each represents a hydrogen atom or C_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom);

C_1-6an alkylsulfinyl group;

c which may be substituted by halogen atoms_1-6An alkylsulfonyl group; or

Arylsulfonyl which may be substituted by a halogen atom,

R⁵⁶to represent

A hydrogen atom;

a halogen atom;

can be: can be represented by "C_1-6Alkyl or halogen atoms "substituted aryl, pyridyl, thienyl or heterocyclic groups_1-10An alkyl group;

C_1-6a haloalkyl group;

C_3-10a cycloalkyl group;

C_1-10an alkoxy group;

C_2-6an alkenyl group;

can be selected from C_1-6Alkyl group, halogen atom, C_1-6Aryl substituted with 1 to 3 groups of alkoxy and nitro;

can be covered with C_1-6An alkyl-substituted heterocyclic group;

C_1-6an alkanoyl group;

C_1-6an alkylsulfinyl group;

C_1-6an alkylsulfonyl group;

arylsulfonyl which may be substituted by a halogen atom;

a hydroxyl group;

a cyano group; or

The nitro group(s),

R⁵⁷to represent

A hydrogen atom;

c which may be substituted by "pyridyl or thienyl_1-10An alkyl group;

C_1-6a haloalkyl group;

C_3-10a cycloalkyl group;

a halogen atom;

C_2-6an alkenyl group;

an aryl group which may be substituted with a halogen atom;

C_1-10an alkoxy group;

C_1-6an alkanoyl group; or

C_1-6An alkylsulfinyl group which is a substituent of a fatty acid,

m represents an integer of 1 to 3 }

a and b each represent 0 or 1,

w represents-CO-, -CO-NH-, -CS-NH-or-SO₂-。]

Another embodiment of the present invention provides a cannabinoid receptor agonist comprising an imine compound represented by the following formula (I-1) or a pharmaceutically acceptable salt thereof as an active ingredient.

[ CHEM 6 ]

[ in the formula, A¹Represents any one of rings represented by the following formulae (wherein X represents an oxygen atom or a sulfur atom),

[ CHEM 7 ]

R¹¹To represent

A hydrogen atom;

a halogen atom;

C_1-6an alkyl group;

C_2-6an alkenyl group;

C_1-6a haloalkyl group;

C_1-6an alkoxy group; or

formula-N (R)⁶)R⁷(in the formula, R⁶And R⁷Each represents a hydrogen atom or C_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom),

R²¹and R³¹Respectively represent

A hydrogen atom;

a halogen atom; or

C_1-6An alkyl group, a carboxyl group,

R⁴¹to represent

May be substituted by halogen atoms, C_3-10Cycloalkyl, aryl or C_1-6Alkoxy-substituted C_1-10Alkyl or C_2-6An alkenyl group, which is a radical of an alkenyl group,

R⁵¹to represent

C_1-6An alkoxy group;

C_1-6a haloalkyl group;

may be selected from halogen atoms, C_3-10Cycloalkyl, may be selected from "C_1-6Alkyl radical, C_1-6Alkoxy radical, C_1-6Aryl or aryloxy substituted with 1 to 5 groups of haloalkyl group and halogen atom' and C substituted with 1 to 3 groups of heterocyclic group_1-10Alkyl or C_2-6An alkenyl group;

a group represented by the formula (II-1),

[ CHEM 8 ]

{ wherein, B represents

C_3-10A cycloalkyl group;

an aryl group;

a heterocyclic group;

a fluorenyl group; or

A group represented by the formula (IV-1),

[ CHEM 9 ]

(in the formula, Y¹Is represented by- (CH)₂) p-or-O- (CH)₂) q-O-, p represents an integer of 2 to 4, q represents an integer of 1 to 3)

R⁵⁵¹And R⁵⁶¹Respectively represent

A hydrogen atom;

a halogen atom;

can be: an aryl, heterocyclic or aryloxy group which may be substituted by halogen atoms, or of the formula-N (R)⁶²)R⁷²(in the formula, R⁶²And R⁷²Each represents a hydrogen atom or C_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom) or a pharmaceutically acceptable salt thereof_1-10An alkyl group;

C_1-6a haloalkyl group;

C_1-10an alkoxy group;

C_1-6an alkylthio group;

C_1-6a haloalkoxy group;

C_3-10a cycloalkyl group;

C_2-6an alkenyl group;

can be selected from C_1-6Alkyl radical, C_1-6Haloalkyl group, halogen atom, C_1-6Aryl substituted with 1 to 3 groups of alkoxy and nitro;

can be covered with C_1-6An alkyl-substituted heterocyclic group;

aryloxy which may be substituted with halogen atom;

formula-N (R)⁶³⁴)R⁷³⁴(in the formula, R⁶³⁴And R⁷³⁴Each represents a hydrogen atom, C_1-6Alkyl, aryl or C_1-6Alkanoyl or a group which forms a cyclic amino group together with an adjacent nitrogen atom);

a hydroxyl group;

a cyano group;

a nitro group;

C_1-6an alkanoyl group;

C_2-6a haloalkanoyl group;

C_1-6an alkylsulfonyl group; or

Arylsulfonyl which may be substituted by a halogen atom,

R⁵⁷¹to represent

A hydrogen atom;

C_1-10an alkyl group;

C_1-10an alkoxy group; or

A halogen atom,

m represents an integer of 1 to 3, a and b each represent 0 or 1, W represents CO or SO₂。]

Another embodiment of the present invention provides an imine compound represented by the following formula (I-1) or a pharmaceutically acceptable salt thereof.

[ CHEM 10 ]

[ in the formula, A¹Represents any one of rings represented by the following formulae (wherein X represents an oxygen atom or a sulfur atom),

[ CHEM 11 ]

R¹¹To represent

A hydrogen atom;

a halogen atom;

C_1-6an alkyl group;

C_2-6an alkenyl group;

C_1-6a haloalkyl group;

C_1-6an alkoxy group; or

formula-N (R)⁶)R⁷(in the formula, R⁶And R⁷Each represents a hydrogen atom or C_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom),

R²¹and R³¹Respectively represent

A hydrogen atom;

a halogen atom; or

C_1-6An alkyl group, a carboxyl group,

R⁴¹to represent

May be substituted by halogen atoms, C_3-10Cycloalkyl, aryl or C_1-6Alkoxy-substituted C_1-10Alkyl or C_2-6An alkenyl group, which is a radical of an alkenyl group,

R⁵¹to represent

C_1-6An alkoxy group;

C_1-6a haloalkyl group;

may be selected from halogen atoms, C_3-10Cycloalkyl, may be selected from "C_1-6Alkyl radical, C_1-6Alkoxy radical, C_1-6Aryl or aryloxy substituted with 1 to 5 groups of haloalkyl group and halogen atom' and C substituted with 1 to 3 groups of heterocyclic group_1-10Alkyl or C_2-6An alkenyl group;

a group represented by the formula (II-1),

[ CHEM 12 ]

{ wherein, B represents

C_3-10A cycloalkyl group;

an aryl group;

a heterocyclic group;

a fluorenyl group; or

A group represented by the formula (IV-1),

[ CHEM 13 ]

(in the formula, Y¹Is represented by- (CH)₂) p-or-O- (CH)₂) q-O-, p represents an integer of 2 to 4, q represents an integer of 1 to 3)

R⁵⁵¹And R⁵⁶¹Respectively represent

A hydrogen atom;

a halogen atom;

can be: an aryl, heterocyclic or aryloxy group which may be substituted by halogen atoms, or of the formula-N (R)⁶²)R⁷²(in the formula, R⁶²And R⁷²Each represents a hydrogen atom or C_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom) or a pharmaceutically acceptable salt thereof_1-10An alkyl group;

C_1-6a haloalkyl group;

C_1-10an alkoxy group;

C_1-6an alkylthio group;

C_1-6a haloalkoxy group;

C_3-10a cycloalkyl group;

C_2-6an alkenyl group;

can be selected from C_1-6Alkyl radical, C_1-6Haloalkyl group, halogen atom, C_1-6Aryl substituted with 1 to 3 groups of alkoxy and nitro;

can be covered with C_1-6An alkyl-substituted heterocyclic group;

aryloxy which may be substituted with halogen atom;

formula-N (R)⁶³⁴)R⁷³⁴(in the formula, R⁶³⁴And R⁷³⁴Each represents a hydrogen atom, C_1-6Alkyl, aryl or C_1-6Alkanoyl or a group which forms a cyclic amino group together with an adjacent nitrogen atom);

a hydroxyl group;

a cyano group;

a nitro group;

C_1-6an alkanoyl group;

C_2-6a haloalkanoyl group;

C_1-6an alkylsulfonyl group; or

Arylsulfonyl which may be substituted by a halogen atom,

R⁵⁷¹to represent

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group; or

C_1-10An alkoxy group,

m represents an integer of 1 to 3, a and b each represent 0 or 1, W represents CO or SO₂]

Another embodiment of the present invention provides a cannabinoid receptor agonist comprising an imine compound represented by the formula (I-2) or a pharmaceutically acceptable salt thereof as an active ingredient.

[ CHEM 14 ]

[ in the formula, R¹²And R²²Respectively represent

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group;

C_1-6a haloalkyl group;

C_1-6an alkoxy group;

a carboxyl group;

C_2-6an alkoxycarbonyl group;

hydroxy radical C_1-6An alkyl group;

aryl which may be substituted with 1 to 3 halogen atoms; or

formula-CON (R)⁶¹)R⁷¹(in the formula, R⁶¹And R⁷¹Each represents a hydrogen atom or C which may be substituted by a cyclic amino group_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom), or R¹¹And R²²Taken together with adjacent carbon atoms to form a radical which may be substituted by C_1-6Alkyl or halogen atom substituted benzene ring, pyridine ring or cyclohexene ring,

R⁴²to represent

May be substituted by halogen atoms, cyano groups, carboxyl groups, C_2-6Alkoxycarbonyl group, C_3-10Cycloalkyl radicals, optionally substituted by "C_1-6Haloalkyl, C_1-6Haloalkoxy, C_1-6Haloalkylthio, carboxy, C_2-6Alkoxycarbonyl or piperidino-aminomethylAcyl-substituted aryl, arylthio, C_1-6Alkoxy or of the formula-CON (R)⁶²)R⁷²(in the formula, R⁶²And R⁷²Each represents a hydrogen atom or C_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom) or a pharmaceutically acceptable salt thereof_1-10Alkyl or C_2-6An alkenyl group; or

C_2-6An alkynyl group,

R⁵²to represent

A hydrogen atom;

C_1-6an alkoxy group;

C_1-6a haloalkyl group;

may be selected from halogen atoms, C_3-10Cycloalkyl radical, C_2-6Alkoxycarbonyl, can be substituted by "C_1-6Alkoxy or aryl "substituted C_1-6Alkoxy radical, may be substituted by C_1-6Alkyl substituted C_3-10Cycloalkoxy, which may be selected from "C_1-6Alkyl radical, C_1-6Haloalkyl, C_1-6Aryl or aryloxy substituted with 1 to 5 groups of alkoxy, aralkyloxy, nitro and halogen atoms', heterocyclic group, phthalimido group, C_1-6Alkanoyloxy, aralkyloxy, C_1-6Alkylthio, arylthio and-N (R)⁶²)R⁷²(in the formula, R⁶²And R⁷²Each represents a hydrogen atom or C_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom) and 1 to 3 groups of the group represented by (A) and (B)_1-10Alkyl or C_2-6An alkenyl group;

can be covered with C_1-6Alkyl radical, C_1-6Alkoxy radical, C_2-6Alkoxycarbonyl or C_1-6Haloalkyl-substituted aryloxy;

an aralkyloxy group;

a group represented by the formula (II-2),

[ CHEM 15 ]

{ wherein, B represents

C_3-10A cycloalkyl group;

an aryl group;

a heterocyclic group;

C_2-6a cyclic amino group;

a fluorenyl group;

2-oxopyrrolidinyl;

a group represented by the formula (III);

[ CHEM 16 ]

(wherein n represents 0 or 1)

Or a group represented by the formula (IV-2),

[ CHEM 17 ]

(in the formula, Y²Is represented by- (CH)₂)p-、-CO-CH₂-CH₂-、-O-CH₂-CH ═ CH-or-O- (CH)₂) q-O-, p represents an integer of 2 to 4, q represents an integer of 1 to 3),

R⁵⁵²to represent

A hydrogen atom;

a halogen atom;

can be: aryl, aryloxy groups which may be substituted by halogen atomsOr formula-N (R)⁶²)R⁷²(in the formula, R⁶²And R⁷²Each represents a hydrogen atom or C_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom) or a pharmaceutically acceptable salt thereof_1-10An alkyl group;

C_1-6a haloalkyl group;

C_1-10an alkoxy group;

C_1-6an alkylthio group;

C_1-6an alkylsulfonyl group;

can be covered with C_1-6An arylthio group substituted with an alkyl group or a halogen atom;

can be covered with C_1-6Arylsulfonyl substituted with an alkyl group or a halogen atom;

C_1-6a haloalkoxy group;

C_1-6a haloalkylthio group;

C_3-10a cycloalkyl group;

C_2-6an alkenyl group;

C_1-6alkoxy radical C_1-6An alkoxy group;

can be selected from C_1-6Alkyl radical, C_1-6Haloalkyl group, halogen atom, C_1-6Aryl substituted with 1 to 3 groups of alkoxy and nitro;

can be covered with C_1-6Alkyl or C_1-6A haloalkyl substituted heterocyclic group;

aryloxy which may be substituted with halogen atom;

formula-N (R)⁶³)R⁷³(in the formula, R⁶³And R⁷³Each represents a hydrogen atom, C_1-6Alkyl radical, C_1-6Hydroxyalkyl radical, C_1-6Alkoxy radical C_1-6Alkyl, aryl, C_1-6Alkanoyl or benzoyl, orA group which is bonded to an adjacent nitrogen atom to form a cyclic amino group);

a hydroxyl group;

a cyano group;

a nitro group;

a carboxyl group;

C_2-6an alkoxycarbonyl group;

c which may be substituted by aralkyl or aryl_2-6A cyclic amino group;

formula-CON (R)⁶⁴)R⁷⁴(in the formula, R⁶⁴And R⁷⁴Each represents a hydrogen atom, C_1-6Alkyl radical, C_1-6Alkoxy radical C_1-6Alkyl, or may be substituted by C_1-6An alkyl-substituted heterocyclic group, or a group which represents a cyclic amino group bonded together with an adjacent nitrogen atom);

formula-SO₂N(R⁶²)R⁷²(in the formula, R⁶²And R⁷²Each represents a hydrogen atom or C_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom);

c which may be substituted by halogen atoms_1-6An alkylsulfonyl group;

arylsulfonyl which may be substituted by a halogen atom; or

2-oxa-3-oxobicyclo [2.2.1] heptyl,

R⁵⁶²to represent

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group;

C_1-6a haloalkyl group; or

C_1-6An alkoxy group,

R⁵⁷²to represent

A hydrogen atom;

C_1-10an alkyl group;

C_1-6a haloalkyl group;

a halogen atom; or

C_1-6An alkoxy group,

m represents an integer of 1 to 3, X represents an oxygen atom or a sulfur atom, and W represents CO or SO₂。]

Other embodiments of the present invention provide imine compounds or pharmaceutically acceptable salts thereof,

wherein, in the following formula (I-2),

[ CHEM 18 ]

W is the radical of CO,

R¹²is composed of

A halogen atom;

C_1-6an alkyl group;

C_1-6a haloalkyl group;

C_1-6an alkoxy group;

a carboxyl group;

C_2-6an alkoxycarbonyl group;

hydroxy radical C_1-6An alkyl group;

aryl which may be substituted with 1 to 3 halogen atoms; or

formula-CON (R)⁶¹)R⁷¹(in the formula, R⁶¹And R⁷¹Each represents a hydrogen atom or C which may be substituted by a cyclic amino group_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom),

R²²is composed of

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group;

C_1-6a haloalkyl group; or

Aryl, or R¹²And R²²Taken together with adjacent carbon atoms to form a radical which may be substituted by C_1-6Alkyl or halogen atom substituted benzene ring, pyridine ring or cyclohexene ring,

R⁴²is C_3-10Cycloalkyl or C_1-6Alkoxy-substituted C_1-10Alkyl or C_2-6An alkenyl group, which is a radical of an alkenyl group,

x and R⁵²The same as above.

Another embodiment of the present invention provides a cannabinoid receptor agonist comprising an imine compound represented by the formula (I-3) or a pharmaceutically acceptable salt thereof as an active ingredient.

[ CHEM 19 ]

[ in the formula, the dotted line indicates that any one of them is a double bond,

X³represents C (R)¹³) The oxygen content of the oxygen-containing gas is S or O,

R¹³、R²³and R³³Respectively represent

A hydrogen atom;

c which may be substituted by aryl groups substituted by halogen atoms_1-10An alkyl group;

C_1-6alkyl halidesA group;

C_3-10a cycloalkyl group; or

Aryl or aralkyl which may be substituted by 1 to 3 halogen atoms, or X³Is C (R)¹³) When R is¹³And R²³Taken together to represent-CH₂-S-CH₂A group represented by (wherein, X³When is S or O, R³³Is unsubstituted) is used,

R⁴³to represent

1, 1-dioxotetrahydrothienyl;

can be selected from C_3-10Cycloalkyl radical, C_1-6Haloalkyl and C_1-6C substituted by radicals of alkoxy_1-10Alkyl or C_2-6An alkenyl group; or an aromatic group, or a salt thereof,

R⁵³to represent

A hydrogen atom;

C_1-10an alkoxy group;

C_1-6alkoxy radical C_1-6An alkoxy group;

C_1-6a haloalkyl group;

can be selected from C_1-6Alkoxy radical, C_3-10Cycloalkyl radical, C_2-6Alkoxycarbonyl, can be selected from "C_1-6Aryl or aryloxy group substituted with 1 to 5 groups of alkoxy group and halogen atom ", heterocyclic group, C_1-6Alkanoyloxy, aralkyloxy and C_1-61-3 radical substituted C of alkylthio group_1-10Alkyl or C_2-6An alkenyl group;

a group represented by the formula (II-3),

[ CHEM 20 ]

{ wherein, B represents

C_3-10A cycloalkyl group;

an aryl group;

a heterocyclic group;

C_2-6a cyclic amino group;

a group represented by the formula (III);

[ CHEM 21 ]

(wherein N represents 0 or 1.)

Or a group represented by the formula (IV-3),

[ CHEM 22 ]

(in the formula, Y³represents-O-CH₂-CH ═ CH-or-O- (CH)₂) q-O-, q represents an integer of 1 to 3)

R⁵⁵³To represent

A hydrogen atom;

a halogen atom;

an aryl group;

C_1-10an alkyl group;

C_1-6alkanoyloxy group C_1-6An alkyl group;

C_1-6a haloalkyl group;

C_1-10an alkoxy group;

C_1-6an alkylthio group;

C_2-6alkene oxideA group;

C_2-6an alkenylthio group;

C_1-6a haloalkoxy group;

C_1-6a haloalkylthio group;

aryl which may be substituted with 1 to 3 halogen atoms or cyano;

a heterocyclic group;

may be substituted by halogen atoms or C_1-6An alkyl-substituted aryloxy or arylthio group;

formula-N (R)⁶³³)R⁷³³(in the formula, R⁶³³And R⁷³³Each represents a hydrogen atom, C_1-6Alkyl radical, C_1-6Alkanoyl, di-C_1-6Alkylamino radical C_2-6Alkanoyl or may be substituted by C_1-6An alkyl-substituted heterocyclic group, or a group which represents a cyclic amino group bonded together with an adjacent nitrogen atom);

a cyano group;

a nitro group;

C_2-6an alkoxycarbonyl group;

R⁵⁶³to represent

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group; or

C_1-6A halogenated alkyl group,

R⁵⁷³to represent

A hydrogen atom;

C_1-10an alkyl group;

a halogen atom; or

C_1-10An alkoxy group,

m represents an integer of 1 to 3, W represents-CO-, -CO-NH-, -CS-NH-or-SO₂-。]

Another embodiment of the present invention provides an imine compound represented by the formula (I-3) or a pharmaceutically acceptable salt thereof.

[ CHEM 23 ]

[ in the formula, the dotted line represents that any one of them is a double bond,

X³represents C (R)¹³) The oxygen content of the oxygen-containing gas is S or O,

R¹³、R²³and R³³Respectively represent

A hydrogen atom;

c which may be substituted by aryl groups substituted by halogen atoms_1-10An alkyl group;

C_1-6a haloalkyl group;

C_3-10a cycloalkyl group; or

Aryl or aralkyl which may be substituted by 1 to 3 halogen atoms, or X³Is C (R)¹³) When R is¹³And R²³Taken together to represent-CH₂-S-CH₂A group represented by (wherein, X³When is S or O, R³³Is unsubstituted) is used,

R⁴³to represent

1, 1-dioxotetrahydrothienyl;

can be selected from C_3-10Cycloalkyl radical, C_1-6Haloalkyl and C_1-6C substituted by radicals of alkoxy_1-10Alkyl or C_2-6An alkenyl group; or an aromatic group, or a salt thereof,

R⁵³to represent

A hydrogen atom;

C_1-10an alkoxy group;

C_1-6alkoxy radical C_1-6An alkoxy group;

C_1-6a haloalkyl group;

can be selected from C_1-6Alkoxy radical, C_3-10Cycloalkyl radical, C_2-6Alkoxycarbonyl, can be selected from "C_1-6Aryl or aryloxy group substituted with 1 to 5 groups of alkoxy group and halogen atom ", heterocyclic group, C_1-6Alkanoyloxy, aralkyloxy and C_1-61-3 radical substituted C of alkylthio group_1-10Alkyl or C_2-6An alkenyl group;

a group represented by the formula (II-3),

[ CHEM 24 ]

{ wherein, B represents

C_3-10A cycloalkyl group;

an aryl group;

a heterocyclic group;

C_2-6a cyclic amino group;

a group represented by the formula (III);

[ CHEM 25 ]

(wherein n represents 0 or 1)

Or a group represented by the formula (IV-3),

[ CHEM 26 ]

(in the formula, Y³represents-O-CH₂-CH ═ CH-or-O- (CH)₂) q-O-, q represents an integer of 1 to 3)

R⁵⁵³To represent

A hydrogen atom;

a halogen atom;

an aryl group;

C_1-10an alkyl group;

C_1-6alkanoyloxy group C_1-6An alkyl group;

C_1-6a haloalkyl group;

C_1-10an alkoxy group;

C_1-6an alkylthio group;

C_2-6an alkenyloxy group;

C_2-6an alkenylthio group;

C_1-6a haloalkoxy group;

C_1-6a haloalkylthio group;

aryl which may be substituted with 1 to 3 halogen atoms or cyano;

a heterocyclic group;

may be substituted by halogen atoms or C_1-6An alkyl-substituted aryloxy or arylthio group;

formula-N (R)⁶³³)R⁷³³(in the formula, R⁶³³And R⁷³³Each represents a hydrogen atom, C_1-6Alkyl radical, C_1-6Alkanoyl, di-C_1-6Alkylamino radical C_2-6Alkanoyl or may be substituted by C_1-6An alkyl-substituted heterocyclic group, or a group which forms a cyclic amino group together with the adjacent nitrogen atomGroup) represents a group;

a cyano group;

a nitro group;

C_2-6an alkoxycarbonyl group;

R⁵⁶³to represent

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group; or

C_1-6A halogenated alkyl group,

R⁵⁷³to represent

A hydrogen atom;

C_1-10an alkyl group;

a halogen atom; or

C_1-10An alkoxy group,

m represents an integer of 1 to 3, W represents-CO-, -CO-NH-, -CS-NH-or-SO₂-。]

In the present invention, R⁴、R⁴¹、R⁴²Or R⁴³Preferably C_2-6Alkenyl or by "C_3-10Cycloalkyl or C_1-10Alkoxy "substituted C_1-10Alkyl, more preferably C_3-10Cycloalkyl-substituted C_1-10An alkyl group.

In the present invention, R is preferably⁵、R⁵¹、R⁵²Or R⁵³Can be selected from C_3-10Cycloalkyl radicals, optionally substituted by "C_1-6C substituted with 1 to 3 groups selected from among aryl, thienyl, halogen atom and aryloxy groups substituted with haloalkyl groups and halogen atoms_1-10Alkyl or C_2-6Alkenyl, or a group represented by the formula (II), (II-1), (II-2) or (II-3), R⁵⁵、R⁵⁵¹、R⁵⁵²Or R⁵⁵³Is a hydrogen atom; a halogen atom; c_1-10An alkyl group; c_1-6A haloalkyl group; c_1-10An alkoxy group; c_1-6A haloalkoxy group; c_3-10A cycloalkyl group; an aryl group; can be covered with C_1-6An alkyl-substituted heterocyclic group; an aryloxy group; morpholinyl; an arylamino group; a cyano group; c_1-6An alkanoyl group; c_2-6A haloalkanoyl group; or C_1-6Alkylsulfonyl radical, R⁵⁶、R⁵⁶¹、R⁵⁶²Or R⁵⁶³Is a hydrogen atom; a halogen atom; c_1-6A haloalkyl group; or C_1-6Alkoxy radical, R⁵⁷、R⁵⁷¹、R⁵⁷²Or R⁵⁷³Is a hydrogen atom; a halogen atom; c_1-10Alkyl or C_1-10Alkoxy compounds.

More preferably R⁵、R⁵¹、R⁵²Or R⁵³Are respectively a group represented by the formula (II), (II-1), (II-2) or (II-3), B is phenyl, R is⁵⁵、R⁵⁵¹、R⁵⁵²Or R⁵⁵³Is a halogen atom; c_1-6An alkyl group; c_1-6A haloalkyl group; c_1-6An alkoxy group; c_1-6A haloalkoxy group; c_3-8A cycloalkyl group; an aryl group; an aryloxy group; morpholinyl; an arylamino group; a cyano group; c_1-6An alkanoyl group; c_2-6A haloalkanoyl group; or C_1-6Alkylsulfonyl radical, R⁵⁶、R⁵⁶¹、R⁵⁶²Or R⁵⁶³Is a hydrogen atom; a halogen atom; c_1-6A haloalkyl group; or C_1-6Alkoxy radical, R⁵⁷、R⁵⁷¹、R⁵⁷²Or R⁵⁷³Is a hydrogen atom; a halogen atom; c_1-6Alkyl or C_1-6Alkoxy, compounds in which m is 1, most preferably R⁵、R⁵¹、R⁵²Or R⁵³Is selected from halogen atoms, C_1-6Alkyl radical, C_1-6Haloalkyl, C_1-6Alkoxy, cyano and C_1-6A phenyl group substituted with 1 to 3 groups of the haloalkoxy group.

In the formula (I) (I-1) (I-2) and (I-3), the configuration of the double bond formed by the carbon atom and the nitrogen atom of the group represented by > C ═ N — CO — is preferably the (Z) configuration.

The imine compound of the present invention also includes a prodrug, a hydrate, and a solvate thereof.

The meanings of the terms used in the present specification are explained below.

In the present invention, "C_X-Y"means that the group following it has from X to Y carbon atoms.

"halogen atom" is fluorine, chlorine, bromine or iodine.

“C_1-6The "alkyl group" is a linear or branched alkyl group having 1 to 6 carbon atoms, and examples thereof include a methyl group, an ethyl group, a n-propyl group, an isopropyl group, a n-butyl group, a 2-butyl group, a tert-butyl group, a 1, 1-dimethylethyl group, a n-pentyl group, an isopentyl group, a 1, 1-dimethylpropyl group, and a n-hexyl group.

“C_1-10The alkyl group is a linear or branched alkyl group having 1 to 10 carbon atoms, except for the above-mentioned group "C_1-6Examples of the "alkyl group" may include 1, 1, 3, 3-tetramethylbutyl, n-nonyl, n-decyl and the like.

“C_1-6Haloalkyl "is as defined above" C_1-6The "alkyl group substituted with 1 or more halogen atoms" may, for example, be a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a 2, 2, 2-trifluoroethyl group, a 2, 2, 2-trichloroethyl group, a pentafluoroethyl group, a 3, 3, 3-trifluoropropyl group, a perfluoropropyl group, a 4-fluorobutyl group, a 4-chlorobutyl group, a 4-bromobutyl group, a perfluorohexyl group or the like.

“C_1-6The "alkoxy group" is a linear or branched alkoxy group having 1 to 6 carbon atoms, and may, for example, be a methoxy group, an ethoxy group, a 1-propoxy group, an isopropoxy group, a 1-butoxy group, a 1-methyl-1-propoxy group, a tert-butoxy group or a 1-pentyloxy group.

“C_1-10The alkoxy group is a linear or branched alkoxy group having 1 to 10 carbon atoms, except for the above-mentioned group "C_1-6Specific examples of the "alkoxy group" may include 1, 1, 3, 3-tetramethylbutoxy group, n-decyloxy group and the like.

The "aryl" is an aromatic carbocyclic group having 6 to 18 carbon atoms and having a monocyclic to 4-membered ring, and examples thereof include phenyl, naphthyl, anthryl (anthryl), phenanthryl, tetracenyl, and pyrenyl. Phenyl is preferred.

“C_3-10The "cycloalkyl group" is a cycloalkyl group having 3 to 10 carbon atoms, and examples thereof include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and adamantyl.

“C_2-6The "alkenyl group" is a linear or branched alkyl group having 2 to 6 carbon atoms and having 1 or more double bonds at any position of the "alkyl group", and examples thereof include a vinyl group, a 1-propenyl group, a 2-butenyl group, a 1, 3-butadienyl group, a 2-pentenyl group, a 3-pentenyl group, and a 2-hexenyl group.

“C_2-6The "alkynyl group" means a straight-chain or branched alkynyl group having 2 to 6 carbon atoms, and may, for example, be an ethynyl group, a 1-propynyl group or a 2-propynyl group.

“C_2-6The "alkoxycarbonyl group" refers to a group obtained by bonding the above-mentioned alkoxy group to a carbonyl group, and examples thereof include a methoxycarbonyl group, an ethoxycarbonyl group, and a tert-butoxycarbonyl group.

"hydroxy group C_1-6The "alkyl group" means C as defined above substituted with 1 to 2 hydroxyl groups_1-6Examples of the alkyl group include a hydroxymethyl group, a 2-hydroxyethyl group and a 4-hydroxybutyl group.

The "cyclic amino group" is a cyclic amino group having 2 to 6 carbon atoms, and may, for example, be a pyrrolidinyl group, a piperidino group, a piperazinyl group, a morpholinyl group or a thiomorpholinyl group. In a thiomorpholinyl group, a dioxide of a sulfur atom is also included in the present invention.

“C_1-6Haloalkoxy "is as above" C_1-6The "alkoxy group substituted with 1 or more halogen atoms" may be exemplified by fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2, 2, 2-trifluoroethoxy, 2, 2, 2-trichloroethoxy, pentafluoroethoxy, perfluoropropoxy, 4-fluorobutoxy, m,4-chlorobutoxy, 4-bromobutoxy, perfluorohexyloxy and the like.

“C_1-6The "alkylthio group" is a straight-chain or branched-chain alkylthio group having 1 to 6 carbon atoms, and examples thereof include a methylthio group, an ethylthio group, a n-propylthio group, an isopropylthio group, a n-butylthio group, a 2-butylthio group, a tert-butylthio group, a 1, 1-dimethylethylthio group, a n-pentylthio group, an isopentylthio group, a 1, 1-dimethylpropylthio group, and a n-hexylthio group.

“C_1-6Haloalkylthio "as defined above" C_1-6The "alkylthio group" which is substituted by 1 or more halogen atoms, may, for example, be a fluoromethylthio group, a difluoromethylthio group, a trifluoromethylthio group, a 2, 2, 2-trifluoroethylthio group, a 2, 2, 2-trichloroethylthio group, a pentafluoroethylthio group, a 4-fluorobutylthio group, a 4-chlorobutylthio group, a 4-bromobutylthio group, a perfluorohexylthio group or the like.

Examples of the "arylthio" may include phenylthio and naphthylthio.

“C_2-6The "alkenylthio" is a linear or branched alkenylthio having 2 to 6 carbon atoms, and examples thereof include an vinylthio group, a 1-propenylthio group, a 2-butenylthio group, a 1, 3-butadienylthio group, a 2-pentenylthio group, a 3-pentenylthio group and a 2-hexenylthio group.

“C_1-6The "alkanoyl group" is a linear or branched alkanoyl group having 1 to 6 carbon atoms, and may, for example, be a formyl group, an acetyl group, a propionyl group, an isopropionyl group, a butyryl group or a pivaloyl group.

“C_1-6Alkanoyloxy "means C as defined above_1-6Examples of the group formed by bonding an alkanoyl group to an oxy group include an acetoxy group, a propionyloxy group and a pivaloyloxy group.

“C_1-6Alkanoyloxy group C_1-6Alkyl "means C as defined above_1-6Alkanoyloxy group with C_1-6Examples of the group to which an alkyl group is bonded include acetoxyethyl, propionyloxymethyl and pivaloyloxymethyl.

“C_2-6Haloalkanoyl groupIs "C_2-6Examples of the "alkanoyl group substituted with a halogen atom" may include fluoroacetyl group, trifluoroacetyl group, 2, 2, 2-trifluoropropionyl group, 2, 2, 2-trichloropropionyl group, 4-fluorobutyryl group, 4-chlorobutyryl group and 4-bromobutyryl group.

“C_1-6Alkoxy radical C_1-6Alkoxy "means 2C_1-6Examples of the group to which an alkoxy group is bonded include methoxymethoxy, methoxypropoxy, ethoxypropoxy and heptyloxyethoxy.

“C_1-6Alkoxy radical C_1-6Alkyl "means C_1-6Alkoxy radicals and C_1-6Examples of the group to which an alkyl group is bonded include methoxymethyl, methoxypropyl, ethoxypropyl and heptyloxyethyl.

The "aryloxy group" is a group in which the above-mentioned "aryl group" is substituted by an oxygen atom, and may, for example, be a phenoxy group or a naphthoxy group.

The "aralkyl group" refers to a group obtained by bonding an aryl group to an alkyl group, and may, for example, be a benzyl group, a phenethyl group or a naphthylmethyl group.

The "aralkyloxy group" refers to a group obtained by bonding an aralkyl group to an oxy group, and examples thereof include a benzyloxy group, a phenethyloxy group, and a naphthylmethoxy group.

The "heterocyclic group" is a monocyclic heterocyclic group or a fused heterocyclic group containing 1 to 3 atoms selected from a nitrogen atom, an oxygen atom and a sulfur atom as ring-forming atoms, and also includes a saturated heterocyclic group, an aromatic heterocyclic group and a fused ring heterocyclic group in which the aromatic heterocyclic group has a partially saturated monocyclic ring. In addition, a fused ring heterocyclic group having a partially saturated monocyclic ring may be substituted with ═ O. The heterocyclic group is preferably a heterocyclic ring having 5 to 10 atoms in the ring.

Examples of the saturated heterocyclic group include an aziridinyl group, an azetidinyl group, a pyrrolidinyl group, an imidazolidinyl group, a pyrazolidinyl group, an oxolanyl group, a thiolanyl group, a piperidyl group, a piperazinyl group, and a morpholinyl group.

As the aromatic heterocyclic group, there may be exemplified pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, quinolyl, isoquinolyl, thienyl (e.g., 2-thienyl, 3-thienyl), pyrrolyl (e.g., 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl), thiazolyl (e.g., 2-thiazolyl, 4-thiazolyl, 5-thiazolyl), isothiazolyl (e.g., 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl), pyrazolyl (e.g., 1-pyrazolyl, 3-pyrazolyl, 4-pyrazolyl), imidazolyl (e.g., 1-imidazolyl, 2-imidazolyl, 3-imidazolyl), furyl (e.g., 2-furyl, 3-furyl), oxazolyl (e.g., 2-oxazolyl, 4-oxazolyl, 5-oxazolyl), isoxazolyl (e.g., 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl), "oxadiazolyl (e.g., 1, 2, 3-oxadiazolyl, 1, 3, 4-oxadiazolyl), thiadiazolyl (e.g., 1, 2, 3-thiadiazolyl, 1, 3, 4-thiadiazolyl), triazolyl (e.g., 1, 2, 4-triazolyl), benzofuranyl (e.g., 2-benzofuranyl, 3-benzofuranyl, 4-benzofuranyl, 5-benzofuranyl), benzothienyl (e.g., 2-benzothienyl, 3-benzothienyl, 4-benzothienyl, 5-benzothienyl), indolyl (e.g., 2-indolyl, 3-indolyl, 4-indolyl, 5-indolyl), benzoxazolyl (e.g., 2-benzoxazolyl, 4-benzoxazolyl, 5-benzoxazolyl, 6-benzoxazolyl), benzisoxazolyl (e.g., 3-benzo [ c ] isoxazolyl, 4-benzo [ c ] isoxazolyl, 5-benzo [ c ] isoxazolyl, 6-benzo [ c ] isoxazolyl, 3-benzo [ d ] isoxazolyl, 4-benzo [ d ] isoxazolyl, 5-benzo [ d ] isoxazolyl, 6-benzo [ d ] isoxazolyl), indazolyl (e.g., 3-indazolyl, 4-indazolyl, 5-indazolyl, 6-indazolyl), benzimidazolyl (e.g., 2-benzimidazolyl, 4-benzimidazolyl, 5-benzimidazolyl, 6-benzimidazolyl), benzooxadiazolyl (e.g., 4-benzo [1, 2, 5] oxadiazolyl, 5-benzo [1, 2, 5] oxadiazolyl, 4-benzo [1, 2, 3] oxadiazolyl, 5-benzo [1, 2, 3] oxadiazolyl), benzothiadiazolyl (e.g., 4-benzo [1, 2, 5] thiadiazolyl, 5-benzo [1, 2, 5] thiadiazolyl, 4-benzo [1, 2, 3] thiadiazolyl, 5-benzo [1, 2, 3] thiadiazolyl), indolizinyl (e.g., 1-indolizinyl, 2-indolizinyl, 3-indolizinyl, 5-indolizinyl), thienopyridyl (e.g., 2-thieno [2, 3-b ] pyridyl group, 3-thieno [2, 3-b ] pyridyl group, 5-thieno [2, 3-b ] pyridyl group, 6-thieno [2, 3-b ] pyridyl group, 2-thieno [3, 2-b ] pyridyl group, 3-thieno [3, 2-b ] pyridyl group, 5-thieno [3, 2-b ] pyridyl group, 6-thieno [3, 2-b ] pyridyl group), pyrazolopyridyl group (e.g., 2-pyrazolopyridyl group, 3-pyrazolopyridyl group, 5-pyrazolopyridyl group, 6-pyrazolopyridyl group), imidazopyridyl group (e.g., 1-imidazo [1, 5-a ] pyridyl group, 3-imidazo [1, 5-a ] pyridyl group, 5-imidazo [1, 5-a ] pyridyl group, 7-imidazo [1, 5-a ] pyridyl group, 2-imidazo [1, 2-a ] pyridyl group, 3-imidazo [1, 2-a ] pyridyl group, 5-imidazo [1, 2-a ] pyridyl group, 7-imidazo [1, 2-a ] pyridyl group), imidazopyrazinyl group (e.g., 1-imidazo [1, 5-a ] pyrazinyl group, 3-imidazo [1, 5-a ] pyrazinyl group, 5-imidazo [1, 5-a ] pyrazinyl group, 8-imidazo [1, 5-a ] pyrazinyl group, 2-imidazo [1, 2-a ] pyrazinyl group, 3-imidazo [1, 2-a ] pyrazinyl group, 5-imidazo [1, 2-a ] pyrazinyl group, 8-imidazo [1, 2-a ] pyrazinyl), pyrazolopyrimidinyl (e.g., 2-pyrazolo [1, 5-a ] pyrimidinyl, 3-pyrazolo [1, 5-a ] pyrimidinyl, 5-pyrazolo [1, 5-a ] pyrimidinyl, 6-pyrazolo [1, 5-a ] pyrimidinyl, 2-pyrazolo [1, 5-c ] pyrimidinyl, 3-pyrazolo [1, 5-c ] pyrimidinyl, 4-pyrazolo [1, 5-c ] pyrimidinyl, 5-pyrazolo [1, 5-c ] pyrimidinyl), triazolopyrimidinyl (e.g., 3- [1, 2, 3] triazolo [1, 5-a ] pyrimidinyl, 5- [1, 2, 3] triazolo [1, 5-a ] pyrimidinyl, 6- [1, 2, 3] triazolo [1, 5-a ] pyrimidinyl, 3- [1, 2, 3] triazolo [1, 5-c ] pyrimidinyl, 4- [1, 2, 3] triazolo [1, 5-c ] pyrimidinyl, 5- [1, 2, 3] triazolo [1, 5-c ] pyrimidinyl, 2- [1, 2, 41 triazolo [1, 5-a ] pyrimidinyl, 5- [1, 2, 4] triazolo [1, 5-a ] pyrimidinyl, 6- [1, 2, 4] triazolo [1, 5-a ] pyrimidinyl, 7- [1, 2, 4] triazolo [1, 5-a ] pyrimidinyl, 2- [1, 2, 4] triazolo [1, 5-c ] pyrimidinyl, 5- [1, 2, 4] triazolo [1, 5-c ] pyrimidinyl, 7- [1, 2, 4] triazolo [1, 5-c ] pyrimidinyl, 8- [1, 2, 4] triazolo [1, 5-c ] pyrimidinyl), thienothienyl (e.g., 2-thieno [2, 3-b ] thienyl, 3-thieno [2, 3-b ] thienyl, 2-thieno [3, 2-b ] thienyl, 3-thieno [3, 2-b ] thienyl), imidazothiazolyl (e.g., 2-imidazo [2, 1-b ] thiazolyl, 3-imidazo [2, 1-b ] thiazolyl, 5-imidazo [2, 1-b ] thiazolyl, 2-imidazo [5, 1-b ] thiazolyl, 3-imidazo [5, 1-b ] thiazolyl, 5-imidazo [5, 1-b ] thiazolyl), and the like.

Examples of the condensed-ring heterocyclic group having a partially saturated monocyclic ring as the aromatic heterocyclic group may include a tetrahydrobenzofuranyl group, a tetrahydrobenzothienyl group, a tetrahydrobenzopyranyl group, a 2, 3-dihydro-1H-benzofuranyl group, a 2, 3-dihydro-1H-benzothienyl group, a 2, 3-dihydro-1H-indolyl group, a 2, 3-dihydro-1H-indazolyl group, a 2, 3-dihydro-1H-benzotriazolyl group, 2, 3-dihydro-1H-benzoxazolyl, 2, 3-dihydro-1H-benzothiazolyl, benzo [1, 3] oxathiyl, benzo [1, 3] dioxolyl (dioxolyl), 2H-chromenyl, chromanyl, indolinyl, isoindolinyl, and the like.

Examples of the condensed ring heterocyclic group having a partially saturated monocyclic ring and substituted with ═ O include a 2-oxo-1, 3-dihydro-1H-indolyl ring, a 3-oxo-1, 2-dihydro-1H-indazolyl ring, a 2-oxo-3H-benzoxazolyl ring, a 2-oxo-3H-benzothiazolyl ring, a 2-oxo-benzo [1, 3] oxathiyl ring, a 2-oxo-benzo [1, 3] dioxolyl ring and a 2-oxo-chromenyl ring.

As the heterocyclic group of ring B, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, quinolyl and isoquinolyl are preferable.

“C_1-6Alkylsulfinyl "is the above-mentioned" C_1-6Examples of the "alkyl group" which may be substituted by SO include methylsulfinyl, ethylsulfinyl, n-propylsulfinyl, n-butylsulfinyl, tert-butylsulfinyl and n-pentylsulfinyl.

"C which may be substituted by halogen atoms_1-6Alkylsulfonyl "being above" C_1-6Alkyl "or" C "above_1-6Examples of the "haloalkyl" which may be substituted by a sulfonyl group include methylsulfonyl and ethylsulfonylAcyl, n-propylsulfonyl, n-butylsulfonyl, t-butylsulfonyl, n-pentylsulfonyl, fluoromethylsulfonyl, difluoromethylsulfonyl, trifluoromethylsulfonyl, 2, 2, 2-trifluoroethylsulfonyl, 2, 2, 2-trichloroethylsulfonyl, pentafluoroethylsulfonyl, 4-fluorobutylsulfonyl, 4-chlorobutylsulfonyl, 4-bromobutylsulfonyl and the like.

The "arylsulfonyl group which may be substituted with a halogen atom" is a sulfonyl group in which the above-mentioned aryl group may be substituted with a halogen atom, and examples thereof include benzenesulfonyl group, 4-chlorobenzenesulfonyl group, 4-fluorobenzenesulfonyl group, 2, 4-dibromobenzenesulfonyl group, 2, 4-difluorobenzenesulfonyl group, naphthalenesulfonyl group and 6-bromonaphthalenesulfonyl group.

"prodrug" refers to a compound that hydrolyzes in vivo to regenerate an imine compound having a cannabinoid receptor agonistic action.

The "pharmaceutically acceptable salt" includes acid addition salts and base addition salts, and examples of the acid addition salts include inorganic acid salts such as hydrochloride, hydrobromide and sulfate, and organic acid salts such as citrate, oxalate, malate, tartrate, fumarate, maleate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, benzoate, aspartate and glutamate. Examples of the base addition salt include inorganic base salts such as sodium salt, calcium salt, magnesium salt, calcium salt and aluminum salt, organic base salts such as ethanolamine salt, lysine salt, ornithine salt, meglumine salt and tris salt, and ammonium salts.

Best mode for carrying out the invention

The compound of the present invention can be produced according to the following steps (1) to (4).

(1) The compound (Ia) of the present invention can be produced, for example, from the amine compound (V) by a method represented by the following reaction formula.

[ CHEM 27 ]

[ reaction scheme, A, R¹、R²、R³、R⁴、R⁵A and b have the same meanings as above, Q¹Represents a halogen atom such as a hydroxyl group, a chlorine atom, a bromine atom or the like; q²W represents a leaving group such as a chlorine atom, a bromine atom, an iodine atom, a methanesulfonyloxy group, a trifluoromethanesulfonyloxy group, a p-toluenesulfonyloxy group or the like, and¹represents-CO-, -CO-or-SO₂-。]

Step 1: preparation of amide Compound (VII)

(i) The amide compound (VII) can be produced by amidation reaction of the compound (VI) with the amine compound (V).

Q of Compound (VI)¹In the case of a halogen atom, the reaction is preferably carried out in the presence of a base. Examples of the base to be used include alkali metal hydroxides (e.g., lithium hydroxide, sodium hydroxide, and potassium hydroxide), alkali metal carbonates (e.g., lithium carbonate, sodium carbonate, and potassium carbonate), alkali metal bicarbonates (e.g., sodium bicarbonate and potassium bicarbonate), organic bases (e.g., triethylamine, diisopropylethylamine, tri-n-butylamine, and 1, 5-diazabicyclo [4.3.0]]-5-nonene, 1, 8-diazabicyclo [5.4.0]7-undecene, pyridine, N-dimethylaminopyridine, etc.), and the like.

The reaction temperature is preferably a temperature from the cooling condition to the boiling point of the solvent or reagent used, and particularly preferably from-20 ℃ to room temperature.

In addition, the reaction can be carried out without solvent or in a solvent. Examples of the solvent to be used include dioxane, tetrahydrofuran, diethyl ether, petroleum ether, N-hexane, cyclohexane, benzene, toluene, xylene, chlorobenzene, pyridine, acetonitrile, ethyl acetate, ethyl methyl ketone, N-dimethylformamide, dimethyl sulfoxide, dichloromethane, chloroform, carbon tetrachloride, and water.

The kind and amount of the solvent and reagent used in the reaction are preferably selected appropriately according to the substrate and reaction conditions used in the reaction.

Further, Q of Compound (VI)¹In the case of a hydroxyl group, a condensing agent is preferably used, and examples of the condensing agent include acid halides such as thionyl chloride and oxalyl chloride, alkyl chloroformates such as ethyl chloroformate, dicyclohexylcarbodiimide, carbodiimide compounds such as 1-ethyl-3- (3-dimethylamino) propylcarbodiimide, sulfonyl chloride compounds such as methanesulfonyl chloride, phosphorus compounds such as diphenylphosphoryl chloride, triphenylphosphine-azodicarboxylic acid diethyl ester, and N, N' -carbonyldiimidazole.

The reaction can be carried out without solvent or in a solvent. Examples of the solvent to be used include methanol, ethanol, N-propanol, isopropanol, N-butanol, t-butanol, dioxane, tetrahydrofuran, diethyl ether, petroleum ether, N-hexane, cyclohexane, benzene, toluene, xylene, chlorobenzene, pyridine, ethyl acetate, N-dimethylformamide, dimethyl sulfoxide, dichloromethane, chloroform, carbon tetrachloride and water.

The kind and amount of the solvent and reagent used in the reaction are preferably selected appropriately according to the substrate and reaction conditions used in the reaction.

(ii) W of Compound (VI)¹In the case of-CO-or-CO-, the amide compound (VII) can be produced by using an acid anhydride or mixed acid anhydride of the compound (VI) in place of the compound (VI).

The reaction is preferably carried out in the presence of a base, and examples of the base to be used include alkali metal hydroxides (lithium hydroxide, sodium hydroxide, potassium hydroxide, etc.), alkali metal carbonates (lithium carbonate, sodium carbonate, potassium carbonate, etc.), alkali metal hydrogencarbonates (sodium hydrogencarbonate, potassium hydrogencarbonate, etc.), organic bases (triethylamine, diisopropylethylamine, tri-N-butylamine, 1, 5-diazabicyclo [4.3.0] -5-nonene, 1, 8-diazabicyclo [5.4.0] -7-undecene, pyridine, N-dimethylaminopyridine, etc.), and the like.

The reaction temperature is preferably a temperature from the cooling condition to the boiling point of the solvent or reagent used.

In addition, the reaction can be carried out without solvent or in a solvent. Examples of the solvent to be used include methanol, ethanol, N-propanol, isopropanol, N-butanol, t-butanol, dioxane, tetrahydrofuran, diethyl ether, petroleum ether, N-hexane, cyclohexane, benzene, toluene, xylene, chlorobenzene, pyridine, acetonitrile, ethyl acetate, ethyl methyl ketone, N-dimethylformamide, dimethyl sulfoxide, dichloromethane, chloroform, carbon tetrachloride and water.

The kind and amount of the solvent and reagent used in the reaction are preferably selected appropriately according to the substrate and reaction conditions used in the reaction.

Step 2: preparation of Compound (Ia) of the present invention

The compound (Ia) of the present invention can be produced by reacting the amide compound (VII) with the compound (VIII).

The reaction is preferably carried out in the presence of a base, and examples of the base to be used include alkali metal hydroxides (lithium hydroxide, sodium hydroxide, potassium hydroxide, etc.), alkali metal carbonates (lithium carbonate, sodium carbonate, potassium carbonate, etc.), alkali metal hydrogencarbonates (sodium hydrogencarbonate, potassium hydrogencarbonate, etc.), alkali metal hydrides (sodium hydride, potassium hydride, etc.), alkali metals (sodium metal, potassium metal, etc.), organic bases (triethylamine, diisopropylethylamine, tri-N-butylamine, 1, 5-diazabicyclo [4.3.0] -5-nonene, 1, 8-diazabicyclo [5.4.0] -7-undecene, pyridine, N-dimethylaminopyridine, etc.), aminated alkali metals (sodium amide, etc.), alkali metal alkoxides (sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.), organometallic compounds (N-butyllithium, potassium butoxide, etc.), and the like, Sec-butyllithium, tert-butyllithium, lithium diisopropylamide, sodium bis (trimethylsilyl) amide, etc.), and the like.

The reaction temperature is preferably a temperature from the cooling condition to the boiling point of the solvent or reagent used.

In addition, the reaction can be carried out without solvent or in a solvent. Examples of the solvent to be used include methanol, ethanol, N-propanol, isopropanol, N-butanol, t-butanol, dioxane, tetrahydrofuran, diethyl ether, petroleum ether, N-hexane, cyclohexane, benzene, toluene, xylene, chlorobenzene, pyridine, ethyl acetate, N-dimethylformamide, dimethyl sulfoxide, dichloromethane, chloroform, and carbon tetrachloride.

The kind and amount of the solvent and reagent used in the reaction are preferably selected appropriately according to the substrate and reaction conditions used in the reaction.

(2) As the compound of the present invention in which W is-CO-NH-or-CS-NH-, W of the amide compound (VII) may be used¹The compound which is-CO-NH-or-CS-NH-can be prepared in the same manner as in the preparation method shown in step 2 of (1).

W of amide Compound (VII)¹Compounds which are-CO-NH-or-CS-NH-can be prepared by reacting an amine compound (V): r⁵-NCO or a compound: r⁵-NCS reaction.

The reaction can be carried out without solvent or in a solvent.

The reaction temperature is preferably a temperature from the cooling condition to the boiling point of the solvent or reagent used, and examples of the solvent used include dioxane, tetrahydrofuran, diethyl ether, petroleum ether, N-hexane, cyclohexane, benzene, toluene, xylene, chlorobenzene, pyridine, acetonitrile, ethyl acetate, ethyl methyl ketone, N-dimethylformamide, dimethyl sulfoxide, dichloromethane, chloroform, carbon tetrachloride, and the like.

The kind and amount of the solvent and reagent used in the reaction are preferably selected appropriately according to the substrate and reaction conditions used in the reaction.

(3) The imine compound represented by the following formula (IX) and the compound (VI) and the compound (I) of the present invention can be used: r⁵-N ═ C ═ O or compounds: r⁵N ═ C ═ S, and was prepared in the same manner as in the preparation method shown in step 1 or (2) of (1) above.

[ CHEM 28 ]

(in the formula, R¹、R²、R³、R⁴A and b have the same meanings as described above. )

The imine compound (IX) can be prepared by hydrolyzing the compound (I) of the present invention.

R⁵Particularly preferred are a hydrogen atom and C_1-10Alkyl radical, C_1-6Examples of the hydrolysis reaction include acid hydrolysis using hydrochloric acid, sulfuric acid, acetic acid, trifluoroacetic acid, methanesulfonic acid, phosphoric acid, polyphosphoric acid, etc., and base hydrolysis using lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium carbonate, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, ammonia, etc., alone or in any combination.

The reaction can be carried out without solvent or in a solvent. Examples of the solvent to be used include methanol, ethanol, N-propanol, isopropanol, N-butanol, t-butanol, dioxane, tetrahydrofuran, diethyl ether, petroleum ether, N-hexane, cyclohexane, benzene, toluene, xylene, chlorobenzene, pyridine, N-dimethylformamide, dimethyl sulfoxide, dichloromethane, chloroform, carbon tetrachloride and water.

The reaction temperature is preferably a temperature from the cooling condition to the boiling point of the solvent or reagent used, and particularly preferably from 0 ℃ to 100 ℃.

In the hydrolysis reaction, the kind and amount of the solvent and reagent to be used are preferably selected appropriately in accordance with the substrate to be used for the reaction and the reaction conditions.

(4) The compound of the present invention represented by the following formula (Ib) can be produced according to the production methods of the following (i) and (ii).

[ CHEM 29 ]

(in the formula, R¹、R²、R³、R⁴、R⁵、R¹³And W is as defined above. )

(i) A compound represented by a pyrazole compound (X): r²-Q³(in the formula, R²As defined above, Q³A leaving group such as a chlorine atom, a bromine atom, an iodine atom, a methanesulfonyloxy group, a trifluoromethanesulfonyloxy group, a p-toluenesulfonyloxy group, etc.) in the presence or absence of a base, and a compound (Ib) of the present invention can be produced.

[ CHEM 30 ]

(in the formula, R¹、R⁴、R⁵、R¹³And W is as defined above. )

Examples of the base to be used include alkali metal hydroxides (e.g., lithium hydroxide, sodium hydroxide, and potassium hydroxide), alkali metal carbonates (e.g., lithium carbonate, sodium carbonate, and potassium carbonate), alkali metal bicarbonates (e.g., sodium bicarbonate and potassium bicarbonate), alkali metal hydrides (e.g., sodium hydride and potassium hydride), alkali metals (e.g., sodium metal and potassium metal), organic bases (e.g., triethylamine, diisopropylethylamine, tri-N-butylamine, 1, 5-diazabicyclo [4.3.0] -5-nonene, 1, 8-diazabicyclo [5.4.0] -7-undecene, pyridine, N-dimethylaminopyridine), aminated alkali metals (e.g., sodium amide), alkali metal alkoxides (e.g., sodium methoxide, sodium ethoxide, and potassium tert-butoxide), and organic metal compounds (e.g., N-butyllithium, sec-butyllithium, tert-butyllithium, lithium diisopropylamide, and potassium diisopropylamide), Sodium bis (trimethylsilyl) amide, etc.), and the like.

The reaction temperature is preferably a temperature from the cooling condition to the boiling point of the solvent or reagent used.

In addition, the reaction can be carried out without solvent or in a solvent. Examples of the solvent to be used include dioxane, tetrahydrofuran, diethyl ether, petroleum ether, N-hexane, cyclohexane, benzene, toluene, xylene, chlorobenzene, pyridine, ethyl acetate, N-dimethylformamide, dimethyl sulfoxide, dichloromethane, chloroform, and carbon tetrachloride.

The kind and amount of the solvent and reagent used in the reaction are preferably selected appropriately according to the substrate and reaction conditions used in the reaction.

(ii) A compound used in the production method represented by the above (4) or (i): r²-Q³With the compound: (R)²O)₂SO₂(in the formula, R²The same as above. ) Instead, the reaction is carried out in the same manner, and the compound (Ib) of the present invention can be produced.

In addition, in the production of the compound of the present invention, depending on the kind of the functional group, it may be effective in production to protect the functional group or to convert the functional group into a group which can be easily converted into the functional group, for a raw material or an intermediate in the production process. Examples of such a functional group include an amino group, a hydroxyl group, and a carboxyl group. The protecting group may be a protecting group commonly used for an amino group, a hydroxyl group, a carboxyl group or the like, and the reaction temperature, the kind of solvent and the reagent used, and the amount thereof to be used in the protecting and deprotecting operation are preferably selected appropriately depending on the substrate and the reaction conditions used in the reaction.

The compounds of the invention may be administered orally or non-orally. The administration forms thereof include tablets, capsules, granules, powders, dusts, troches, ointments, creams, emulsions, suspensions, suppositories, injections and the like, and can be produced according to conventional preparation techniques (for example, the method prescribed in japanese pharmacopoeia 14 th edition). These administration forms can be appropriately selected depending on the symptoms, age and therapeutic purpose of the patient. In the production of various dosage forms of preparations, commonly used excipients (e.g., crystalline cellulose, starch, lactose, mannitol, etc.), binders (e.g., hydroxypropyl cellulose, polyvinylpyrrolidone, etc.), lubricants (e.g., magnesium stearate, talc, etc.), disintegrants (e.g., carboxymethylcellulose calcium, etc.), and the like can be used.

The dose of the compound of the present invention is 1 to 2000mg per day for treating an adult, and the compound is administered 1 time per day or several times per day. The dosage can be increased or decreased according to the age, weight and symptoms of the patient.

Examples

The present invention will be specifically described below with reference to examples and test examples, but the present invention is not limited thereto.

Example 1

Preparation of 1-cyclopropylmethyl-2- (trifluoroacetylimino) -1, 2-dihydropyridine (Compound No.1)

[ CHEM 31 ]

Trifluoroacetic anhydride (3.3ml) was added to a chloroform (20ml) solution of 2-aminopyridine (2.0g) and pyridine (1.9ml) under ice-cooling, followed by stirring at room temperature for 3 days. The reaction mixture was washed (with water and saturated brine in this order), dried (anhydrous sodium sulfate), filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: n-hexane-ethyl acetate 3: 1) to give 2- (trifluoroacetylamino) pyridine (2.3g) as a colorless liquid.

The obtained 2- (trifluoroacetylamino) pyridine (1.3g) was dissolved in N, N-dimethylformamide (13ml), and sodium iodide (0.01g), 60% sodium hydride (0.27g) and cyclopropylmethyl bromide (1.1g) were added thereto at room temperature, followed by stirring with heating at 50 ℃ for 5 hours. The reaction mixture was allowed to return to room temperature, water was added thereto, and the mixture was extracted (ethyl acetate), washed (saturated brine), dried (anhydrous sodium sulfate), filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: chloroform-methanol ═ 18: 1), whereby 1-cyclopropylmethyl-2- (trifluoroacetylimino) -1, 2-dihydropyridine (1.4g) was obtained as colorless crystals.

¹H-NMR, MS (ESI) and melting point are shown in Table 8.

Example 2

Preparation of 1-cyclopropylmethyl-2- {3- (trifluoromethyl) benzoylimino } -1, 2-dihydropyridine (Compound No.2)

(1) 1-cyclopropylmethyl-2-imino-1, 2-dihydropyridines

[ CHEM 32 ]

1-Cyclopropylmethyl-2- (trifluoroacetylimino) -1, 2-dihydropyridine (1.1g) prepared according to the preparation method shown in example 1 was dissolved in methanol (25ml), and an aqueous solution prepared by dissolving anhydrous potassium carbonate (1.2g) in water (12.5ml) was added at room temperature, followed by stirring for 2 hours. The reaction solution (ethyl acetate) was extracted, dried (anhydrous sodium sulfate), filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: chloroform-methanol ═ 18: 1), whereby 1-cyclopropylmethyl-2-imino-1, 2-dihydropyridine (0.5g) was obtained as a yellow liquid.

¹H-NMR(200MHz，CHLOROFORM-d)d ppm；0.31-0.37(m，2H)，0.58-0.67(m，2H)，1.23-1.43(m，1H)，3.69(d，J＝6.0Hz，2H)，5.70(m，1H)，6.29(d，J＝8.0，1H)，6.76(m，1H)，7.04(m，1H)

MS(ESI)(Positive)m/z；149(M+H)⁺

(2) 1-Cyclopropylmethyl-2- {3- (trifluoromethyl) benzoylimino } -1, 2-dihydropyridine (Compound No.2)

[ CHEM 33 ]

To a chloroform (2ml) solution of 1-cyclopropylmethyl-2-imino-1, 2-dihydropyridine (0.20g) and triethylamine (0.19ml) was added 3- (trifluoromethyl) benzoyl chloride (0.24ml) under ice-cooling, and the mixture was stirred at room temperature for 17 hours. To the reaction mixture was added water, followed by extraction (chloroform), drying (anhydrous sodium sulfate), filtration, and concentration of the filtrate under reduced pressure, and the resulting residue was purified by silica gel column chromatography (developing solvent: n-hexane-ethyl acetate: 3: 1) to give 1-cyclopropylmethyl-2- {3- (trifluoromethyl) benzoylimino } -1, 2-dihydropyridine (0.44g) as a colorless solid.

¹H-NMR, MS (ESI) and melting point are shown in Table 8.

Example 3

Preparation of 1-cyclopropylmethyl-2- {3- (trifluoromethyl) phenylsulfonylimino } -1, 2-dihydropyridine (Compound No.50)

[ CHEM 34 ]

Following the procedure described in example 2, 3- (trifluoromethyl) phenylsulfonyl chloride was used instead of 3- (trifluoromethyl) benzoyl chloride, 1-cyclopropylmethyl-2- {3- (trifluoromethyl) phenylsulfonylimino } -1, 2-dihydropyridine was obtained as a colorless solid.

¹The H-NMR, Mass and melting point are shown in Table 8.

The compounds Nos. 3-49 and 51-59 shown in Table 1, the compounds Nos. 60, 71-107, 116-174, 178-213, 215-342, 343-351 and 369-372 shown in Table 2, and the compounds No.504-515 shown in Table 3 were prepared according to the preparation methods shown in examples 1 and 2.

Of these compounds¹H-NMR, Mass and melting points are shown in Table 8, Table 9 and Table 11.

Example 4

Preparation of 5-tert-butyl-3- (2-ethoxyethyl) -4-methyl-2- (3-trifluoromethylbenzoyl) imino-2, 3-dihydrothiazole (Compound No.352)

(1) 5-tert-butyl-4-methyl-2- (3-trifluoromethylbenzoyl) aminothiazole

[ CHEM 35 ]

A solution of 2-amino-5-tert-butyl-4-methylthiazole (1.0g), 3- (trifluoromethyl) benzoic acid (1.2g), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide monohydrochloride (1.2g) and 1-hydroxybenzotriazole monohydrate (1.0g) in N, N-dimethylformamide (10ml) was stirred at room temperature for 48 hours. To the reaction mixture was added ethyl acetate, washed (2M hydrochloric acid, 2M aqueous sodium hydroxide solution, and saturated brine in this order), dried (anhydrous sodium sulfate), filtered, and the filtrate was concentrated under reduced pressure to give 5-tert-butyl-4-methyl-2- (3-trifluoromethylbenzoyl) aminothiazole (1.7g) as a yellow amorphous form.

¹H-NMR(200MHz，CHLOROFORM-D)d ppm；1.42(s，9H)，2.20(s，3H)，7.55(t，J＝7.5Hz，1H)，7.78(d，J＝7.5Hz，1H)，8.05(d，J＝7.5Hz，1H)，8.16(s，1H)

MS(ESI)(Positive)m/z；343(M+H)

(2) 5-tert-butyl-3- (2-ethoxyethyl) -4-methyl-2- (3-trifluoromethylbenzoyl) imino-2, 3-dihydrothiazole (Compound No.352)

[ CHEM 36 ]

A solution of 5-tert-butyl-4-methyl-2- (3-trifluoromethylbenzoyl) aminothiazole (0.15g), sodium iodide (0.005g), 60% sodium hydride (0.02g) and 2-ethoxyethyl bromide (0.11g) in N, N-dimethylformamide (1.5ml) was stirred with heating at 50 ℃ for 5 hours. The reaction mixture was allowed to return to room temperature, water was added thereto, and the mixture was extracted (ethyl acetate), washed (saturated brine), dried (anhydrous sodium sulfate), filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: n-hexane-ethyl acetate 5: 1) to give 5-tert-butyl-3- (2-ethoxyethyl) -4-methyl-2- (3-trifluoromethylbenzoyl) imino-2, 3-dihydrothiazole (0.03g) as colorless crystals.

¹The H-NMR, Mass and melting point are shown in Table 9.

The compounds No.384-, 430, 433, 434 and 438-447 shown in Table 2 were prepared according to the preparation method shown in example 3.

Of these compounds¹The H-NMR, Mass and melting point are shown in Table 10.

Example 5

Preparation of N- (5-tert-butyl-3-cyclopropylmethyl-4-methyl-3H-thiazol-2-ylidene) -1-naphthalenesulfonamide (Compound No.383)

(1) N- (5-tert-butyl-4-methylthiazol-2-yl) -1-naphthalenesulfonamide

[ CHEM 37 ]

To a solution of 2-amino-5-tert-butyl-4-methylthiazole (0.12g) and N, N-dimethylaminopyridine (catalyst amount) in pyridine (1.5ml) was added 1-naphthalenesulfonyl chloride (0.19g) under ice-cooling, and the mixture was stirred at room temperature overnight. Water was added to the reaction solution, and the precipitate was collected by filtration and dried. The obtained crude crystals were recrystallized (chloroform-N-hexane) to give N- (5-tert-butyl-4-methylthiazol-2-yl) -1-naphthalenesulfonamide (0.22g) as colorless crystals.

¹H-NMR(200MHz，CHLOROFORM-D)d ppm；1.43(s，9H)，2.36(s，3H)

MS(ESI)(Negative)m/z；265(M-H)^-

(2) N- (5-tert-butyl-3-cyclopropylmethyl-4-methyl-3H-thiazol-2-ylidene) -1-naphthalenesulfonamide (Compound No.383)

[ CHEM 38 ]

A solution of N- (5-tert-butyl-4-methyl-thiazol-2-yl) -1-naphthalenesulfonamide (0.20g), 55% sodium hydride (0.03g), sodium iodide (catalyst amount), and (bromomethyl) cyclopropane (0.11g) in N, N-dimethylformamide (0.5ml) was stirred at room temperature overnight. Water was added to the reaction mixture, followed by extraction (ethyl acetate), washing (water and saturated brine in this order), drying (anhydrous magnesium sulfate), filtration, and concentration of the filtrate under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: N-hexane-ethyl acetate 4: 1), and recrystallized (chloroform-N-hexane) to give N- (5-tert-butyl-3-cyclopropylmethyl-4-methyl-3H-thiazol-2-ylidene) -1-naphthalenesulfonamide (0.12g) as colorless crystals.

¹The H-NMR, Mass and melting point are shown in Table 10.

Example 6

Preparation of 3- (2-aminoethyl) -5-tert-butyl-4-methyl-2- (3-trifluoromethylbenzoyl) imino-2, 3-dihydrothiazole (Compound No.354)

[ CHEM 39 ]

A solution of 3- (2-phthalimidoethyl) -5-tert-butyl-4-methyl-2- (3-trifluoromethylbenzoyl) imino-2, 3-dihydrothiazole (compound No.355) (0.15g) prepared according to the preparation method of example 4 and hydrazine monohydrate (0.2ml) in ethanol (6.3ml) was heated under reflux for 1 hour. The reaction solution was returned to room temperature, and the precipitate was removed by filtration. Chloroform was added to the filtrate, and the mixture was washed (2M aqueous sodium hydroxide solution and saturated brine in this order), dried (anhydrous magnesium sulfate), filtered, and then the filtrate was concentrated under reduced pressure to give 3- (2-aminoethyl) -5-tert-butyl-4-methyl-2- (3-trifluoromethylbenzoyl) imino-2, 3-dihydrothiazole (0.12g) as pale yellow crystals.

¹The H-NMR, Mass and melting point are shown in Table 9.

Example 7

Preparation of 5-carboxy-3-cyclopropylmethyl-4-methyl-2- (3-trifluoromethylbenzoyl) imino-2, 3-dihydrothiazole (Compound No.357)

[ CHEM 40 ]

A1: 1 tetrahydrofuran-ethanol (8ml) solution containing 5-ethoxycarbonyl-3-cyclopropylmethyl-4-methyl-2- (3-trifluoromethylbenzoyl) imino-2, 3-dihydrothiazole (compound No.356) (0.23g) prepared according to the preparation method shown in example 4 and 20% aqueous sodium hydroxide solution (1.25ml) was stirred at room temperature for 1 hour. 3M hydrochloric acid was added to the reaction solution, and after adjusting to acidity, the precipitate was collected by filtration. The obtained solid was dissolved in tetrahydrofuran-chloroform, dried (anhydrous magnesium sulfate), filtered, and the filtrate was concentrated under reduced pressure to give colorless amorphous 5-carboxy-3-cyclopropylmethyl-4-methyl-2- (3-trifluoromethylbenzoyl) imino-2, 3-dihydrothiazole (0.20 g).

¹The H-NMR, Mass and melting point are shown in Table 9.

Compound No.214 shown in Table 2, Compound Nos. 431 and 435 shown in Table 3 were prepared according to the preparation method shown in example 7.

Of these compounds¹H-NMR, Mass and melting points are shown in Table 9, Table 10 and Table 11.

Example 8

Preparation of 3-cyclopropylmethyl-5-isopropylaminocarbonyl 4-methyl-2- (3-trifluoromethylbenzoyl) imino-2, 3-dihydrothiazole (Compound No.358)

[ CHEM 41 ]

The preparation method shown in example 3(1) was followed using 5-carboxy-3-cyclopropylmethyl-4-methyl-2- (3-trifluoromethylbenzoyl) imino-2, 3-dihydrothiazole (compound No.357) prepared according to the preparation method shown in example 7 to give 3-cyclopropylmethyl-5-isopropylaminocarbonyl-4-methyl-2- (3-trifluoromethylbenzoyl) imino-2, 3-dihydrothiazole as a colorless powder.

¹The H-NMR, Mass and melting point are shown in Table 9.

According to the preparation example shown in example 8, using the compound No.356, the compound No.359-361 was prepared.

Compound No.432 was also prepared using compound No. 431.

Compounds No.436 and 437 were also prepared using the compound No. 435.

Of these compounds¹H-NMR, Mass and melting points are shown in tables 9 and 10.

Example 9

Preparation of N- (3-allyl-4, 5-diphenyl-3H-thiazol-2-ylidene) benzamide (Compound No.368)

(1) 1-allyl-3-benzoylthiourea

[ CHEM 42 ]

A solution of benzoyl isothiocyanate (1.4g) and allylamine (0.7ml) in benzene (9ml) was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (developing solvent: n-hexane-ethyl acetate: 10: 1 to 5: 1) to obtain 1-allyl-3-benzoylthiourea (1.9g) as a colorless solid.

¹H-NMR(200MHz，CHLOROFORM-D)d ppm；4.30-4.43(m，2H)，5.21-5.42(m，2H)，5.87-6.09(m，1H)，7.45-7.69(m，3H)，7.78-7.90(m，2H)，9.00(s，1H)，10.80(s，1H)，

MS(ESI)(Negative)m/z；219(M-H)^-

Melting point of 68-69 deg.C

(2) N- (3-allyl-4, 5-diphenyl-3H-thiazol-2-ylidene) benzamide (Compound No.368)

[ CHEM 43 ]

A solution of 1-allyl-3-benzoylthiourea (0.20g) and 2-bromo-1, 2-diphenylethane (0.24g) in toluene (4.5ml) was heated under reflux for 4.5 hours. After the solvent was concentrated under reduced pressure, the obtained residue was purified by silica gel column chromatography (developing solvent: N-hexane-ethyl acetate: 30: 1 to 20: 1), and (N-hexane-ethyl acetate) was recrystallized to obtain N- (3-allyl-4, 5-diphenyl-3H-thiazol-2-ylidene) benzamide (0.13g) as colorless crystals.

¹The H-NMR, Mass and melting point are shown in Table 9.

Example 10

Preparation of N- [1, 2-dihydro-1, 5-dimethyl-2- (2-ethoxyethyl) pyrazol-3-ylidene ] -2-fluoro-3- (trifluoromethyl) benzamide (Compound No.452)

(1) N- (1, 5-dimethylpyrazol-3-yl) -2-fluoro-3- (trifluoromethyl) benzamide

[ CHEM 44 ]

To a chloroform (5ml) solution of 3-amino-1, 5-dimethylpyrazole (0.50g) and triethylamine (0.63ml) was added 2-fluoro-3- (trifluoromethyl) benzoyl chloride (0.65ml) under ice-cooling, and the mixture was stirred at room temperature for 0.5 hour. The reaction mixture was washed (2M aqueous sodium hydroxide solution), dried (anhydrous sodium sulfate), filtered, and the filtrate was concentrated under reduced pressure, and the resulting residue was washed with N-hexane to give N- (1, 5-dimethylpyrazol-3-yl) -2-fluoro-3- (trifluoromethyl) benzamide (1.25g) as a colorless solid.

¹H-NMR(200MHz，CHLOROFORM-D)d ppm；2.30(s，39H)，3.72(s，3H)，6.59(s，1H)，7.40(t，J＝7.5Hz，1H)，7.78(t，J＝7.5Hz，1H)，8.34(td，J＝7.5Hz，1H)，8.60-8.89.(br.s，1H)

MS(ESI)(Positive)m/z；302(M+H)⁺

(2) N- [1, 2-dihydro-1, 5-dimethyl-2- (2-ethoxyethyl) pyrazol-3-ylidene ] -2-fluoro-3- (trifluoromethyl) benzamide

[ CHEM 45 ]

After a suspension of N- (1, 5-dimethylpyrazol-3-yl) -2-fluoro-3- (trifluoromethyl) benzamide (0.50g) and 55% sodium hydride (0.07g) in N, N-dimethylformamide (5ml) was stirred at room temperature for 5 minutes, 2-ethoxyethyl bromide (0.38g) and sodium iodide (catalyst amount) were added and stirred for 17 hours. Water was added to the reaction mixture, which was extracted with ethyl acetate and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (developing solvent: chloroform-methanol 18: 1) to give N- [1, 2-dihydro-1, 5-dimethyl-2- (2-ethoxyethyl) pyrazol-3-ylidene ] -2-fluoro-3- (trifluoromethyl) benzamide (0.01g) as a colorless solid.

¹The H-NMR, Mass and melting point are shown in Table 11.

The compounds No.448-451, 453, 454 and 456 shown in Table 3 were prepared according to the preparation methods shown in example 10.

Of these compounds¹The H-NMR, Mass and melting point are shown in Table 11.

Example 11

Preparation of N- {1, 2-dihydro-1, 5-dimethyl-2- (1, 1-dioxotetrahydrothiophen-3-yl) pyrazol-3-ylidene } -2-fluoro-3- (trifluoromethyl) benzamide (Compound No.455)

(1) N- {2- (1, 1-dioxotetrahydrothiophen-3-yl) -5-methylpyrazol-3-yl } -2-fluoro-3- (trifluoromethyl) benzamide

[ CHEM 46 ]

The procedure described in example 8(1) was followed using 3-amino-2- (1, 1-dioxotetrahydrothiophen-3-yl) -5-methylpyrazole to give N- {2- (1, 1-dioxotetrahydrothiophen-3-yl) -5-methylpyrazol-3-yl) -2-fluoro-3- (trifluoromethyl) benzamide as a colorless solid.

¹H-NMR(600MHz，CHLOROFORM-D)d ppm；2.63-2.69(m，1H)，2.75-2.81(m，1H)，3.12(m，1H)，3.50-3.63(m，3H)，4.89(m，1H)，6.00(s，1H)，7.46(m，1H)，7.87(m，1H)，8.13(d，J＝13.3Hz，1H)，8.33(m，1H)

MS(ESI)(Positive)m/z；406(M+H)⁺

(2) N- {1, 2-dihydro-1, 5-dimethyl-2- (1, 1-dioxotetrahydrothiophen-3-yl) pyrazol-3-ylidene } -2-fluoro-3- (trifluoromethyl) benzamide (Compound No.455)

[ CHEM 47 ]

A solution of N- {2- (1, 1-dioxotetrahydrothiophen-3-yl) -5-methylpyrazol-3-yl } -2-fluoro-3- (trifluoromethyl) benzamide (0.40g) and dimethyl sulfate (0.11ml) in toluene (1.2ml) was stirred with heating at 80 ℃ for 47 hours. The reaction mixture was allowed to return to room temperature and purified by silica gel column chromatography (developing solvent: chloroform-methanol 20: 1) to give colorless amorphous N- {1, 2-dihydro-1, 5-dimethyl-2- (1, 1-dioxotetrahydrothiophen-3-yl) pyrazol-3-ylidene } -2-fluoro-3- (trifluoromethyl) benzamide (0.11 g).

¹The H-NMR, Mass and melting point are shown in Table 11.

The compounds represented by the compound No.497-499 shown in Table 3 were prepared according to the preparation method shown in example 11.

¹The H-NMR, Mass and melting point are shown in Table 11.

Example 12

Preparation of N- (5-tert-butyl-2-cyclopropylmethyl-1, 2-dihydro-1-methylpyrazol-3-ylidene) carboxamide (Compound No.457)

(1) 3-amino-5-tert-butyl-2- (cyclopropylmethyl) pyrazole

[ CHEM 48 ]

Methanesulfonyl chloride (175ml) was added to a chloroform (500ml) solution of cyclopropylmethanol (125g) and triethylamine (315ml) under ice-cooling for 1.5 hours, followed by stirring at room temperature for 2 hours. Water was added to the reaction mixture, followed by extraction (chloroform), washing (water and saturated brine in this order), drying (anhydrous magnesium sulfate), filtration, and concentration of the filtrate under reduced pressure. The obtained residue (232g) was dissolved in ethanol (500ml), and hydrazine 1 hydrate (500g) was added thereto at room temperature, followed by stirring for 17 hours. After the solvent was distilled off under reduced pressure, the mixture was extracted (chloroform), dried (anhydrous magnesium sulfate), filtered, and the filtrate was concentrated under reduced pressure. The resulting yellow oily residue (68g) was dissolved in ethanol (610ml), and after adding 4, 4-dimethyl-3-oxovaleronitrile (99g) at room temperature, it was refluxed for 4 hours. After the solvent was distilled off under reduced pressure, the residue was purified by silica gel column chromatography (developing solvent: n-hexane-ethyl acetate 5: 1), and recrystallized (ethyl acetate-n-hexane) to give 3-amino-5-tert-butyl-2- (cyclopropylmethyl) pyrazole (80g) as a colorless solid.

¹H-NMR(200MHz，CHLOROFORM-d)d ppm；0.26-0.41(m，2H)，0.49-0.62(m，2H)，1.11-1.27(m，1H)，1.26(s，9H)3.42(br.s，2H)，3.86(d，J＝6.2Hz，2H)，5.42(s，1H)

MS(ESI)(Positive)m/z；194(M+H)⁺

The melting point is between 69.5 and 70.5 DEG C

(2) N- (5-tert-butyl-2-cyclopropylmethylpyrazol-3-yl) trifluoroacetamide

[ CHEM 49 ]

After formic acid (3.9ml) and acetic anhydride (7.4ml) were stirred at room temperature for 1 hour, 3-amino-5-tert-butyl-2- (cyclopropylmethyl) pyrazole (5.0g) was added under ice-cooling, and the mixture was stirred at room temperature for 1 hour. To the reaction mixture was added 2M aqueous sodium hydroxide solution, extracted (sodium acetate), washed (water), dried (anhydrous sodium sulfate), filtered, and the filtrate was concentrated under reduced pressure to give N- (5-tert-butyl-2-cyclopropylmethylpyrazol-3-yl) carboxamide (4.4g) as a colorless oil.

¹H-NMR(200MHz，CHLOROFORM-d)d ppm；0.27-0.40(m，2H)，0.50-0.66(m，2H)，1.13-1.27(m，1H)，1.29(s，9H)，3.91(d，J＝6.6Hz，2H)，5.98(s，3H)，6.26(s，3H)，8.26-8.31(m，3H)，8.31-8.39(m，3H)

MS(ESI)(Positive)m/z；222(M+H)⁺

(3) N- (5-tert-butyl-2-cyclopropylmethyl-1, 2-dihydro-1-methylpyrazol-3-ylidene) carboxamide (Compound No.457)

[ CHEM 50 ]

Dimethyl sulfate (0.9ml) was added to a toluene (6ml) solution of N- (5-tert-butyl-2-cyclopropylmethylpyrazol-3-yl) formamide (2.0g), and the mixture was stirred at 50 ℃ for 48 hours. The reaction mixture was allowed to return to room temperature, and a saturated aqueous sodium bicarbonate solution was added thereto, followed by extraction (ethyl acetate), washing (with water and a saturated saline solution in this order), drying (anhydrous magnesium sulfate), filtration, and concentration of the filtrate under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: chloroform-methanol ═ 18: 1), whereby N- (5-tert-butyl-2-cyclopropylmethyl-1, 2-dihydro-1-methylpyrazol-3-ylidene) carboxamide (0.35g) was obtained as a colorless solid.

The 1H-NMR, Mass and melting point are shown in Table 11.

Example 13

Preparation of N- (5-tert-butyl-2-cyclopropylmethylpyrazol-3-yl) trifluoroacetamide (Compound No.458)

(1) N- (5-tert-butyl-2-cyclopropylmethylpyrazol-3-yl) trifluoroacetamide

[ CHEM 51 ]

Using 3-amino-5-tert-butyl-2- (cyclopropylmethyl) pyrazole prepared according to the preparation method shown in example 12(1), the preparation was carried out according to the preparation method shown in example 1 to give N- (5-tert-butyl-2-cyclopropylmethylpyrazol-3-yl) trifluoroacetamide.

¹H-NMR(200MHz，CHLOROFORM-d)d ppm；0.32-0.42(m，2H)，0.65-0.74(m，2H)，1.10-1.36(m，1H)，1.30(s，9H)，3.99(d，J＝6.0Hz，2H)，6.31(s，1H)，8.11-8.23(brs，1H)

MS(ESI)(Negative)m/z；290(M+H)⁺

(2) N- (5-tert-butyl-2-cyclopropylmethylpyrazol-3-yl) trifluoroacetamide (Compound No.458)

[ CHEM 52 ]

According to the production process shown in example 12(3), N- (5-tert-butyl-2-cyclopropylmethylpyrazol-3-yl) trifluoroacetamide was obtained from N- (5-tert-butyl-2-cyclopropylmethylpyrazol-3-yl) trifluoroacetamide.

¹The H-NMR, Mass and melting point are shown in Table 11.

Example 14

Preparation of N- (5-tert-butyl-2-cyclopropylmethyl-1, 2-dihydro-1-methylpyrazol-3-ylidene) -2-chloro-3- (trifluoromethyl) benzamide (Compound No.476)

(1) 5-tert-butyl-2-cyclopropylmethyl-1, 2-dihydro-1-methylpyrazol-3-ylideneamine

[ CHEM 53 ]

A solution of N- (5-tert-butyl-2-cyclopropylmethyl-1, 2-dihydro-1-methylpyrazol-3-ylidene) carboxamide (0.20g) prepared according to the preparation process shown in example 12 and 12M hydrochloric acid (0.3ml) in methanol (3ml) was stirred at room temperature for 2 hours. After adding a 2M aqueous solution of sodium hydroxide to the reaction mixture and making it basic, extraction (chloroform), drying (anhydrous sodium sulfate), filtration and concentration of the filtrate under reduced pressure were carried out to obtain 5-tert-butyl-2-cyclopropylmethyl-1, 2-dihydro-1-methylpyrazol-3-ylideneamine (0.17g) as a yellow amorphous solid.

¹H-NMR(200MHz，CHLOROFORM-d)d ppm；0.28-0.41(m，2H)，0.43-0.55(m，2H)，0.95-1.17(m，1H)，1.29(s，9H)，3.16(s，3H)，3.62(d，J＝6.6Hz，2H)，5.31(s，1H)

MS(ESI)(Negative)m/z；208(M+H)⁺

(2) N- (5-tert-butyl-2-cyclopropylmethyl-1, 2-dihydro-1-methylpyrazol-3-ylidene) -2-chloro-3- (trifluoromethyl) benzamide (Compound No.476)

[ CHEM 54 ]

A solution of 2-chloro-3-trifluoromethylbenzoic acid (0.13g), thionyl chloride (0.07ml) and N, N-dimethylformamide (0.01ml) in tetrahydrofuran (2ml) was heated under reflux for 0.5 hour. After the solvent was distilled off under reduced pressure, chloroform (1ml) was added to the obtained residue to obtain a chloroform solution. The chloroform solution was added to a chloroform (2ml) solution of 5-tert-butyl-2-cyclopropylmethyl-1-methyl-1, 2-dihydropyrazol-3-ylideneamine (0.10g) and triethylamine (0.10ml) at room temperature, and the mixture was stirred for 17 hours. The reaction mixture was washed (saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution in this order), dried (anhydrous magnesium sulfate), filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (developing solvent: ethyl acetate-methanol ═ 5: 1) to give N- (5-tert-butyl-2-cyclopropylmethyl-1, 2-dihydro-1-methylpyrazol-3-ylidene) -2-chloro-3- (trifluoromethyl) benzamide (0.05g) as a colorless solid.

¹The H-NMR, Mass and melting point are shown in Table 11.

The compounds Nos. 459-473, 475, 477-496 and 503 shown in Table 3 were prepared according to the preparation method shown in example 14.

Of these compounds¹The H-NMR, Mass and melting point are shown in Table 11.

Example 15

Preparation of N- (5-tert-butyl-2-cyclopropylmethyl-1, 2-dihydro-1-methylpyrazol-3-ylidene) -2-fluoro-3- (trifluoromethyl) benzamide (Compound No.474)

[ CHEM 55 ]

To a chloroform (120ml) solution of 3-amino-5-tert-butyl-2- (cyclopropylmethyl) pyrazole (12.8g) and triethylamine (9.2ml) was added 2-fluoro-3- (trifluoromethyl) benzoyl chloride (15.0g) under ice-cooling, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was washed (2M aqueous sodium hydroxide solution), dried (anhydrous sodium sulfate), filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: n-hexane-ethyl acetate 3: 1) to obtain a colorless solid (18.3 g). The resulting solid (4.4g) was dissolved in toluene (90ml), and dimethyl sulfate (3.2ml) was added thereto, followed by stirring at 80 ℃ for 17 hours. The reaction mixture was allowed to return to room temperature, and a saturated aqueous sodium bicarbonate solution was added to the reaction mixture, followed by extraction (ethyl acetate), washing (water and saturated brine in this order), drying (anhydrous sodium sulfate), filtration, and concentration of the filtrate under reduced pressure. The resulting residue was purified by silica gel column chromatography (developing solvent: chloroform-methanol 18: 1) to give N- (5-tert-butyl-2-cyclopropylmethyl-1, 2-dihydro-1-methylpyrazol-3-ylidene) -2-fluoro-3- (trifluoromethyl) benzamide (0.3g) as a colorless solid.

¹The H-NMR, Mass and melting point are shown in Table 11.

Example 16

Preparation of N- (5-tert-butyl-2-cyclobutylmethyl-1, 2-dihydro-1-methylpyrazol-3-ylidene) -2-fluoro-3- (trifluoromethyl) benzamide (Compound No.482)

[ CHEM 56 ]

Using 3-amino-5-tert-butyl-2- (cyclobutylmethyl) pyrazole prepared according to the preparation method shown in example 12(1), the preparation was carried out according to the preparation method shown in example 15 to give N- (5-tert-butyl-2-cyclobutylmethyl-1, 2-dihydro-1-methylpyrazol-3-ylidene) -2-fluoro-3- (trifluoromethyl) benzamide.

¹The H-NMR, Mass and melting point are shown in Table 11.

Compounds Nos. 481 and 483-496 shown in Table 3 were prepared by the preparation method shown in example 16.

Of these compounds¹The H-NMR, Mass and melting point are shown in Table 11.

Example 17

Preparation of N- (5-tert-butyl-2-cyclopropylmethyl-1, 2-dihydro-1-methylpyrazol-3-ylidene) -3, 5-difluorophenyloxoacetamide (Compound No.500)

[ CHEM 57 ]

A mixture of 5-tert-butyl-2-cyclopropylmethyl-1, 2-dihydro-1-methylpyrazol-3-ylideneamine (0.080g) prepared by the method for preparation shown in example 14(1) and ethyl 3, 5-difluorophenyloxoacetate (0.2ml) was stirred with heating at 110 ℃ for 7 hours. The mixture was returned to room temperature, and the mixture was purified by silica gel column chromatography (developing solvent: chloroform-methanol ═ 30: 1) followed by thin layer chromatography (developing solvent: N-hexane-ethyl acetate ═ 1: 10) to give N- (5-tert-butyl-2-cyclopropylmethyl-1, 2-dihydro-1-methylpyrazol-3-ylidene) -3, 5-difluorophenyloxoacetamide (0.5mg) as a pale brown amorphous product.

¹The H-NMR, Mass and melting point are shown in Table 11.

Example 18

Preparation of 1- (5-tert-butyl-2-cyclopropylmethyl-1, 2-dihydro-1-methylpyrazol-3-ylidene) -3- { 4-chloro-2- (trifluoromethyl) phenyl } urea (Compound No.501)

[ CHEM 58 ]

A tetrahydrofuran (2ml) solution containing 5-tert-butyl-2-cyclopropylmethyl-1, 2-dihydro-1-methylpyrazol-3-ylideneamine (0.050g) prepared according to the preparation process shown in example 14(1) and 4-chloro-2- (trifluoromethyl) phenyl isocyanate (0.064g) was stirred at room temperature for 20 hours. Water was added to the reaction mixture, followed by extraction (ethyl acetate), washing (with water and saturated brine in this order), drying (anhydrous magnesium sulfate), filtration, and concentration of the filtrate under reduced pressure. The resulting residue was separated and purified by thin layer chromatography (developing solvent: chloroform-methanol 25: 1) to give 1- (5-tert-butyl-2-cyclopropylmethyl-1, 2-dihydro-1-methylpyrazol-3-ylidene) -3- { 4-chloro-2- (trifluoromethyl) phenyl } urea (0.001g) as a pale yellow powder.

¹The H-NMR, Mass and melting point are shown in Table 11.

Example 19

Preparation of 1- (5-tert-butyl-2-cyclopropylmethyl-1, 2-dihydro-1-methylpyrazol-3-ylidene) -3- (4-fluorophenyl) thiourea (Compound No.502)

[ CHEMICAL 59 ]

According to the production method shown in example 18, 1- (5-tert-butyl-2-cyclopropylmethyl-1, 2-dihydro-1-methylpyrazol-3-ylidene) -3- (4-fluorophenyl) thiourea was obtained.

¹The H-NMR, Mass and melting point are shown in Table 11.

Compounds Nos. 1001 to 1431, 2001 to 2678, 3001 to 3158 and 3159 to 3327 shown in tables 4 to 7 were prepared according to the preparation methods shown in example 2(2) or example 14(2) by using imine compounds (1-cyclopropylmethyl-2-imino-1, 2-dihydropyridine, 3-cyclopropylmethyl-2, 3-dihydro-4, 5-dimethylthiazol-2-ylideneamine, 5-tert-butyl-2, 3-dihydro-3, 4-dimethylthiazol-2-ylideneamine, 5-tert-butyl-2, 3-dihydro-3-ethyl-4-methylthiazol-2-ylideneamine, 5-tert-butyl-2, 3-dihydro-3- (2-methoxyethyl) -4-methylthiazol-2-ylideneamine) Amine, 5-tert-butyl-3-cyclopropylmethyl-2, 3-dihydro-4-methylthiazol-2-ylideneamine, 5-tert-butyl-2-cyclopropylmethyl-1, 2-dihydro-1-methylpyrazol-3-ylideneamine and 5-tert-butyl-3-cyclopropylmethyl-2, 3-dihydro-1, 3, 4-thiadiazol-2-ylideneamine).

Mass of the obtained compound is shown in tables 12 to 15.

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TABLE 8
				Compound No.	1H-NMR	Mass	Melting Point (. degree.C.)
1	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.44-0.53(m，2H)0.61-0.71(m，2H)1.30-1.47(m，1H)4.25(d，J＝7.31H，2H)6.82-6.92(m，1H)7.73-7.895(m，2H)8.44-8.51(m，1H)	ESI(Pos)245(M+H)+	90-91
				2	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.42-0.55(m，2H)0.62-0.78(m，2H)1.40-1.60(m，1H)4.24(d，J＝7.47Hz，2H)6.56-6.69(m，1H)7.45-7.75(m，4H)8.38-8.59(m，3H)	ESI(Pos)321(M+H)+	105.5-106.5
3	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.42-0.76(m，4H)1.39-1.56(m，1H)4.22(d，J＝7.0Hz，2H)6.53-6.65(m，1H)7.06-7.22(m，1H)7.52-7.81(m，3H)8.17-8.27(m，1H)8.32-8.43(m，1H)8.58-8.65(m，1H)	ESI(Pos)379(M+H)+	-
				4	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.53-0.73(m，2H)1.23-1.53(m，1H)4.14(d，J＝7.47Hz，2H)6.53-6.68(m，1H)7.20-7.46(m，3H)7.49-7.64(m，1H)7.64-7.77(m，1H)7.85-8.03(m，1H)8.22-8.37(m，1H)	ESI(Pos)337(M+H)+	-
5	1H NMR(200MHz，CHLOROFORM-d)d ppm 3.90(s，3H)6.56-6.70(m，1H)7.18-7.31(m，1H)7.58-7.71(m，3H)8.17-8.29(m，1H)8.37-8.48(m，1H)	ESI(Pos)299(M+H)+	146-147
				6	1H NMR(200MHz，CHLOROFORM-d)d ppm 1.49(t，J＝7.3Hz，3H)4.40(q，J＝7.3Hz，2H)6.60-6.71(m，1H)7.18-7.31(m，1H)7.56-7.69(m，3H)8.16-8.27(m，1H)8.39-8.48(m，1H)	ESI(Pos)313(M+H)+	93-95
7	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.97(t，J＝7.3Hz，3H)1.41(dt，J＝14.8，7.3Hz，2H)1.77-1.97(m，2H)4.34(t，J＝7.5Hz，2H)6.55-6.70(m，1H)7.17-7.31(m，1H)7.55-7.70(m，3H)8.15-8.28(m，1H)8.41-8.50(m，1H)	ESI(Pos)341(M+H)+	51-52
				8	1H NMR(200MHz，CHLOROFORM-d)d ppm 1.47(d，J＝6.6Hz，6H)5.84-6.06(m，1H)6.64-6.77(m，1H)7.18-7.32(m，1H)7.53-7.78(m，2H)8.14-8.45(m，2H)	ESI(Pos)327(M+H)+	86-88

Table 8 (continuation)
				Compound No.	1H-NMR	Mass	Melting Point (. degree.C.)
9	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.38-0.74(m，4H)1.32-1.53(m，1H)4.22(d，J＝7.03Hz，2H)6.61-6.72(m，1H)7.18-7.31(m，1H)7.54-7.76(m，3H)8.13-8.27(m，1H)8.37-8.48(m，1H)	ESI(Pos)339(M+H)+	58.5-59
				10	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.36-0.51(m，2H)0.60-0.74(m，2H)1.29-1.53(m，1H)4.17(d，J＝7.47Hz，2H)6.58-6.74(m，1H)7.16-7.41(m，2H)7.55-7.82(m，3H)8.33-8.45(m，1H)	ESI(Pos)322(M+H)+	53.5-54.5
11	1H NMR(300MHz，CHLOROFORM-d)d ppm 0.35-0.75(m，4H)1.18-1.42(m，1H)4.12(d，J＝7.31Hz，2H)6.61-6.71(m，1H)7.19-7.42(m，2H)7.58-7.85(m，3H)8.30-8.39(m，1H)	ESI(Pos)339(M+H)+	88-89
				12	1H NMR(600MHz，CHLOROFORM-d)d ppm 0.44-0.72(m，4H)0.74-0.90(m，2H)1.84-2.05(m，1H)3.57-3.85(m，2H)6.43-6.57(m，1H)7.22-7.38(m，1H)7.64-7.85(m，3H)8.42-8.55(m，1H)8.70-8.83(m，10H)	ESI(Pos)353(M+H)+	93-94
13	1H NMR(200MHz，CHLOROFORM-d)d ppm -0.00-0.53(m，4H)0.54-0.77(m，1H)1.81(q，J＝7.0Hz，2H)4.43(t，J＝7.0Hz，2H)6.58-6.69(m，1H)7.18-7.31(m，1H)7.55-7.71(m，3H)8.14-8.27(m，1H)8.40-8.51(m，1H)	ESI(Pos)353(M+H)+	56-58
				14	1H NMR(200MHz，CHLOROFORM-d)d ppm 1.12(t，J＝7.03Hz，3H)3.44(q，J＝7.03Hz，2H)3.84(t，J＝4.83Hz，2H)4.54(t，J＝4.83Hz，2H)6.56-6.69(m，1H)7.18-7.31(m，1H)7.57-7.77(m，3H)8.13-8.26(m，1H)8.41-8.50(m，1H)	ESI(Pos)357(M+H)+	104.5-105.5
15	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.41-0.77(m，4H)1.32-1.51(m，1H)4.19(d，J＝7.5Hz，2H)7.20-7.31(m，1H)7.57-7.71(m，2H)7.81-7.87(m，1H)8.14-8.26(m，1H)8.35-8.43(m，1H)	ESI(Pos)439(M+Na)+	124-126
				16	1H NMR(200MHz，CHLOROFORM-d)d ppm 3.21(t，J＝7.3Hz，2H)4.54(t，J＝7.3Hz，2H)6.43-6.55(m，1H)7.10-7.36(m，7H)7.54-7.73(m，2H)8.19-8.32(m，1H)8.45-8.57(m，1H)	ESI(Pos)389(M+H)+	117-118

Table 8 (continuation)
				Compound No.	1H-NMR	Mass	Melting Point (. degree.C.)
17	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.59-0.73(m，2H)1.26-1.46(m，1H)4.13(d，J＝7.47Hz，2H)6.62-6.74(m，1H)7.02-7.17(m，1H)7.39-7.50(m，1H)7.58-7.77(m，3H)8.30-8.41(m，1H)	ESI(Pos)339(M+H)+	88.5-89
				18	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.40-0.56(m，2H)0.56-0.75(m，2H)1.34-1.56(m，1H)4.22(d，J＝7.03Hz，2H)6.59-6.74(m，1H)7.10-7.28(m，1H)7.53-7.79(m，3H)8.29-8.53(m，2H)	ESI(Pos)339(M+H)+	127-127.5
19	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.39-0.51(m，2H)0.60-0.72(m，2H)1.33-1.55(m，1H)3.94(s，3H)4.16(d，J＝7.03Hz，2H)6.55-6.66(m，1H)6.95-7.05(m，1H)7.52-7.72(m，3H)8.09-8.14(m，1H)8.36-8.46(m，1H)	ESI(Pos)351(M+H)+	-
				20	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.36-0.72(m，4H)1.34-1.58(m，1H)3.80(s，3H)3.85(s，3H)4.15(d，J＝7.5Hz，2H)6.48-6.61(m，1H)6.84-6.93(m，2H)7.40-7.46(m，1H)7.46-7.59(m，1H)7.60-7.69(m，1H)8.27-8.38(m，1H)	ESI(Pos)313(M+H)+	-
21	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.38-0.74(m，4H)1.34-1.54(m，1H)4.20(d，J＝7.0Hz，2H)6.65-6.77(m，1H)7.51-7.62(m，1H)7.63-7.80(m，3H)7.84-7.91(m，1H)8.09-8.17(m，1H)8.49-8.59(m，1H)8.81-8.90(m，1H)8.94-9.01(m，1H)	ESI(Pos)304(M+H)+	-
				22	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.40-0.77(m，4H)1.30-1.48(m，1H)2.38(s，3H)4.23(d，J＝7.0Hz，2H)6.79-6.91(m，1H)7.19-7.31(m，1H)7.55-7.69(m，2H)7.75-7.84(m，1H)8.05-8.18(m，1H)	ESI(Pos)353(M+H)+	-
23	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.36-0.51(m，2H)0.56-0.71(m，2H)1.32-1.52(m，1H)2.36(s，3H)4.18(d，J＝7.0Hz，2H)6.48-6.56(m，1H)7.18-7.30(m，1H)7.56-7.67(m，2H)8.14-8.31(m，2H)	ESI(Pos)353(M+H)+	81-83

Table 8 (continuation)
				Compound No.	1H-NMR	Mass	Melting Point (. degree.C.)
24	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.37-0.73(m，4H)1.30-1.55(m，1H)2.25(s，3H)4.21(d，J＝7.5Hz，2H)7.17-7.31(m，1H)7.44-7.69(m，2H)8.10-8.27(m，1H)8.35-8.48(m，1H)	ESI(Pos)353(M+H)+	118-120
				25	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.49-0.62(m，4H)1.20-1.40(m，1H)2.61(s，3H)4.50(d，J＝7.0Hz，2H)6.54(d，J＝7.0Hz，1H)7.19-7.30(m，1H)7.45-7.67(m，2H)8.11-8.31(m，2H)	ESI(Pos)353(M+H)+	96-98
26	1H NMR(600MHz，CHLOROFORM-d)d ppm 0.39-0.45(m，2H)0.67-0.73(m，2H)1.31-1.39(m，1H)4.10(d，J＝7.34Hz，2H)7.47(t，J＝7.79Hz，1H)7.57(t，J＝7.57Hz，1H)7.65(dd，J＝9.40，2.06Hz，1H)7.68(d，J＝7.79Hz，1H)7.76(d，J＝7.79Hz，1H)8.02(s，1H)8.27(d，J＝9.17Hz，1H)	APCI(Pos)389(M+H)+	93-93.5
				27	1H NMR(600MHz，CHLOROFORM-d)d ppm 0.46-0.54(m，2H)0.72-0.80(m，2H)1.44-1.51(m，1H)4.22(d，J＝7.34Hz，2H)7.56(t，J＝7.79Hz，1H)7.64(dd，J＝9.63，2.29Hz.1H)7.73(d，J＝7.79Hz，1H)8.02(s.1H)8.33(d，J＝9.63Hz，1H)8.41(d，J＝7.79Hz.1H)8.51(s，1H)	APCI(Pos)389(M+H)+	84-85
28	1H NMR(600MHz，CHLOROFORM-d)d ppm -1.19- -1.12(m，2H)-0.78- -0.72(m，2H)-0.14--0.04(m，1H)3.46(d，J＝9.2Hz，2H)6.92-6.97(m，1H)7.29-7.34(m，1H)7.75-7.82(m，1H)8.35-8.43(m，2H)8.60-8.64(m，1H)	ESI(Pos)407(M+H)+	-
				29	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.40-0.77(m，4H)1.37-1.52(m，1H)4.22(d，J＝7.5Hz，2H)6.68-6.77(m，1H)7.21-7.33(m，1H)7.61-7.74(m，1H)7.78-7.88(m，1H)8.16-8.30(m，1H)8.65-8.73(m，1H)	ESI(Pos)407(M+H)+	85-86
30	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.40-0.77(m，4H)1.30-1.48(m，1H)2.38(s，3H)4.23(d，J＝7.0Hz，2H)6.79-6.91(m，1H)7.19-7.31(m，1H)7.55-7.69(m，2H)7.75-7.84(m，1H)8.05-8.18(m，1H)	ESI(Pos)353(M+H)+	-

Table 8 (continuation)
				Compound No.	1H-NMR	Mass	Melting Point (. degree.C.)
31	1H NMR(600MHz，CHLOROFORM-d)d ppm 0.42-0.53(m，2H)0.66-0.79(m，2H)1.37-1.48(m，1H)4.20(d，J＝7.34Hz，2H)7.18-7.23(m，1H)7.65-7.70(m，2H)8.03(s，1H)8.36(dd，J＝6.65，2.52Hz，1H)8.39(d，J＝9.63Hz，1H)	APCI(Pos)407(M+H)+	109-110
				32	1H NMR(500MHz，CHLOROFORM-d)d ppm 0.36-0.70(m，4H)1.26-1.37(m，1H)4.30(d，J＝6.9Hz，2H)6.97-7.03(m，1H)7.17-7.22(m，1H)7.22-7.26(m，1H)7.54-7.59(m，1H)7.59-7.64(m，1H)7.66-7.72(m，1H)	ESI(Pos)407(M+H)+	-
33	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.38-0.74(m，4H)1.30-1.49(m，1H)4.17(d，J＝7.0Hz，2H)6.61-6.68(m，1H)7.22-7.32(m，1H)7.59-7.72(m，2H)8.15-8.26(m，1H)8.51-8.56(m，1H)	ESI(Pos)395(M+Na)+	91-93
				34	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.40-0.79(m，4H)1.33-1.52(m，1H)4.20(d，J＝7.5Hz，2H)7.18-7.30(m，1H)7.51-7.71(m，2H)7.72-7.79(m，1H)8.13-8.26(m，1H)8.39-8.51(m，1H)	ESI(Pos)373(M+H)+	117-119
35	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.48-0.67(m，4H)1.35-1.55(m，1H)4.67(d，J＝7.5Hz，2H)6.70-6.76(m，1H)7.20-7.31(m，1H)7.42-7.54(m，1H)7.59-7.70(m，1H)8.12-8.23(m，1H)8.25-8.35(m，1H)	ESI(Pos)373(M+H)+	81-83
				36	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.38-0.83(m，4H)1.32-1.51(m，1H)4.19(d，J＝7.5Hz，2H)7.21-7.33(m，1H)7.59-7.74(m，2H)7.99-8.07(m，1H)8.15-8.28(m，1H)8.30-8.40(m，1H)	ESI(Pos)407(M+H)+	93-94
37	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.41-0.54(m，2H)0.64-0.80(m，2H)1.31-1.51(m，1H)4.23(d，J＝7.5Hz，2H)7.48-7.78(m，3H)8.13-8.27(m，1H)8.49-8.63(m，1H)	ESI(Pos)357(M+H)+	89-91
				38	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.43-0.57(m，2H)0.60-0.77(m，2H)1.39-1.58(m，1H)4.31(d，J＝7.0Hz，2H)7.19-7.32(m，1H)7.35-7.55(m，5H)7.57-7.71(m，1H)7.83-7.98(m，2H)8.15-8.30(m，1H)8.46-8.61(m，1H)	ESI(Pos)415(M+H)+	115-116

Table 8 (continuation)
				Compound No.	1H-NMR	Mass	Melting Point (. degree.C.)
39	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.44-0.54(m，4H)1.28-1.51(m，1H)4.02(s，3H)4.46(d，J＝7.5Hz，2H)6.03-6.09(m，1H)7.17-7.29(m，1H)7.52-7.66(m，2H)7.99-8.09(m，1H)8.12-8.25(m，1H)	ESI(Pos)369(M+H)+	126-128
				40	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.32-0.54(m，4H)1.41-1.58(m，1H)2.73(s，6H)4.49(d，J＝6.6Hz，2H)6.33-6.42(m，1H)7.18-7.29(m，1H)7.49-7.67(m，2H)8.06-8.25(m，2H)	ESI(Pos)382(M+H)+	-
41	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.53-0.63(m，4H)1.12-1.37(m，1H)2.78(s，3H)4.61(d，J＝7.0Hz，2H)7.25(d，1H)7.56-7.73(m，2H)8.05-8.26(m，2H)	ESI(Pos)431(M+H)+	135-137
				42	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.44-0.83(m，4H)1.24-1.45(m，1H)4.16(d，J＝7.0Hz，2H)7.19-7.42(m，2H)7.61-7.71(m，2H)8.13-8.24(m，1H)	ESI(Pos)397(M+Na)+	69-71
43	1H NMR(200MHz，CHLOROFORM-d)d ppm 2.23(s，3H)2.43(s，3H)3.81(s，3H)3.83(s，3H)3.89(s，3H)6.22-6.27(m，1H)6.40-6.53(m，2H)7.93-8.01(m，2H)	ESI(Pos)301(M+H)+	117.5-118
				44	1H NMR(200MHz，CHLOROFORM-d)d ppm 2.27(s，3H)2.46(s，3H)2.63(s，3H)4.97-5.30(m，4H)5.89-6.12(m，1H)6.27(s，1H)7.11-7.32(m，3H)7.86-7.95(m，1H)8.02(s，1H)	ESI(Pos)281(M+H)+	-
45	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.50-0.60(m，4H)1.15-1.37(m，1H)2.30(s，3H)2.56(s，3H)4.46(d，J＝7.0Hz，2H)6.34-6.44(m，1H)7.16-7.28(m，1H)7.54-7.67(m，1H)8.09-8.24(m，2H)	ESI(Pos)367(M+H)+	114-115
				46	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.52-0.62(m，4H)1.14-1.30(m，1H)2.43(s，3H)2.83(s，3H)4.63(d，J＝6.6Hz，2H)7.18-7.29(m，1H)7.56-7.68(m，1H)8.09-8.22(m，1H)8.28(s，1H)	ESI(Pos)445(M+H)+	121-122

Table 8 (continuation)
				Compound No.	1H-NMR	Mass	Melting Point (. degree.C.)
47	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.48-0.73(m，4H)1.23-1.49(m，1H)4.71(d，J＝7.0Hz，2H)7.20-7.45(m，2H)7.62-7.90(m，5H)8.03-8.26(m，2H)	ESI(Pos)411(M+Na)+	125-126
				48	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.42-0.76(m，4H)1.33-1.52(m，1H)4.23(d，J＝7.0Hz，2H)7.06-7.13(m，1H)7.26-7.37(m，1H)7.55-7.82(m，5H)8.21-8.39(m，2H)	ESI(Pos)389(M+H)+	-
49	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.27-0.55(m，4H)1.22-1.44(m，1H)4.19(d，J＝7.0Hz，2H)6.91-6.99(m，1H)7.18-7.32(m，1H)7.51-7.82(m，2H)8.34-8.43(m，2H)	ESI(Pos)340(M+H)+	-
				50	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.28-0.40(2H，m)，0.57-0.69(2H，m)，1.21-1.39(1H，m)，3.98(2H，d，J＝7.47Hz)，6.54-6.64(2H，m)，7.45-7.73(4H，m)，7.76-7.84(1H，m)8.38-8.46(1H，m)	ESI(Pos)356(M+H)+	-
51	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.42-0.69(m，4H)1.19-1.33(m，1H)1.37(s，9H)4.12(d，J＝7.0Hz，2H)7.17(s，1H)7.18-7.28(m，1H)7.57-7.68(m，1H)8.12-8.23(m，1H)	ESI(Pos)342(M+H)+	-
				52	1H NMR(200MHz CHLOROFORM-d)d ppm 0.56-0.69(m，4H)1.20-1.37(m，1H)1.42(d，J＝6.6Hz，6H)3.13-3.31(m，1H)4.24(d，J＝7.0Hz，2H)7.26-7.39(m，1H)7.67-7.80(m，1H)8.27-8.40(m，1H)	ESI(Pos)388(M+H)+	-
53	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.41-0.73(m，4H)1.17-1.41(m，1H)1.36(s，9H)4.17(d，J＝7.0Hz，2H)7.17(s，1H)7.46-7.57(m，1H)7.65-7.73(m，1H)8.38-8.46(m，1H)8.48-8.57(m，1H)	ESI(Pos)367(M+H)+	-
				54	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.42-0.70(m，4H)1.21-1.32(m，1H)1.36(s，9H)4.13(d，J＝7.0Hz，2H)7.11-7.23(m，1H)7.19(s，1H)7.56-7.67(m，1H)8.29-8.37(m，1H)	ESI(Pos)385(M+H)+	-

Table 8 (continuation)
				Compound No.	1H-NMR	Mass	Melting Point (. degree.C.)
55	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.38-0.69(m，4H)1.20-1.34(m，1H)1.35(s，9H)3.93(s，3H)4.09(d，J＝7.5Hz，2H)6.95-7.03(m，1H)7.23(s，1H)7.54-7.62(m，1H)8.05-8.12(m，1H)	ESI(Pos)397(M+H)+	64-65
				56	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.41-0.55(m，2H)0.67-0.81(m，2H)1.20-1.35(m，1H)1.43(s，9H)4.01(d，J＝7.0Hz，2H)7.16-7.32(m，1H)7.56-7.70(m，1H)7.85(s，1H)8.16-8.29(m，1H)	ESI(Pos)401(M+H)+	85-87
57	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.44-0.58(m，2H)0.68-0.83(m，2H)1.21-1.38(m，1H)1.43(s，9H)4.05(d，J＝7.5Hz，2H)7.52(t，J＝7.5Hz，1H)7.69(d，J＝7.5Hz，1H)7.86(s，1H)8.46(d，J＝7.5Hz，1H)8.57(s，1H)	ESI(Pos)383(M+H)+	54-55
				58	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.67-0.80(m，2H)1.19-1.38(m，1H)1.43(s，9H)4.02(d，J＝7.0Hz，2H)7.09-7.28(m，1H)7.55-7.68(m，1H)7.88(s，1H)8.33-8.43(m，1H)	ESI(Pos)401(M+H)+	63-65
59	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.40-0.53(m，52H)0.64-0.80(m，2H)1.18-1.36(m，1H)1.42(s，9H)3.94(s，3H)3.97(d，J＝7.5Hz，2H)6.95-7.05(m，1H)7.52-7.63(m，1H)7.91(s，1H)8.11-8.17(m，1H)	ESI(Pos)413(M+H)+	95-97

TABLE 9

Compound No.	H-NMR	Melting Point (. degree.C.)
			60	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.33-0.84(m，4H)1.14-1.50(m，1H)4.15(d，J＝7.5Hz，2H)6.76(d，J＝4.8Hz，1H)7.12-7.39(m，2H)7.63-7.75(m，1H)8.26-8.39(m，1H)	96-97
61	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.16(t，J＝7.0Hz，3H)，3.49(q，J＝7.0Hz，2H)，3.81(t，J＝4.8Hz，2H)，4.47(t，J＝4.8Hz，2H)，6.70(d，J＝4.4Hz，1H)，7.17-7.36(m，2H)，7.62-7.76(m，1H)，8.25-8.37(m，1H)	199-201
			62	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.41(t，J＝7.0Hz，3H)，2.38(s，3H)，4.32(q，J＝7.0Hz，2H)，6.36(s，1H)，7.27(t，J＝7.7Hz，1H)，7.68(t，J＝7.7Hz，1H)，8.33(t，J＝7.7Hz，1H)	48-50
63	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.38-0.73(m，4H)，1.13-1.42(m，1H)2.41(s，3H)4.20(d，J＝7.0Hz，2H)6.38(s，1H)7.21-7.33(m，1H)7.63-7.74(m，1H)8.26-8.36(m，1H)	109-111
			64	1H NMR(200MHz，CHLOROFORM-D)d ppm 2.33(s，3H)，3.81(s，3H)，6.71(s，1H)，7.32-7.45(m，1H)，8.51-8.59(m，1H)，8.65-8.74(m，1H)，9.51-9.59(m，4H)	173-174
65	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.47(t，J＝7.0Hz，3H)，2.35(s，3H)，4.35(q，J＝7.0Hz，2H)，6.78(s，1H)，7.29(t，J＝7.7Hz，1H)，7.69(t，J＝7.7Hz，1H)，8.30(t，J＝7.7Hz，1H)	90-92
			66	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.38-0.77(m，4H)，1.18-1.43(m，1H)，2.35(s，3H)，4.11(d，J＝7.5Hz，2H)，6.84(s，1H)，7.31-7.42(m，1H)，8.47-8.56(m，1H)，8.62-8.74(m，1H)，9.48-9.54(m，1H)	115-117
67	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.39-0.76(m，4H)1.18-1.42(m，1H)2.32-2.39(m，3H)4.08(d，J＝7.0Hz，2H)6.83-6.89(m，1H)7.19-7.34(m，1H)7.60-7.75(m，1H)8.22-8.37(m，1H)	129-130
			68	1H NMR(200MHz，CHLOROFORM-D)d ppm 2.26(s，6H)3.82(s，3H)7.55(t，J＝7.9Hz，1H)7.71(d，J＝7.9Hz，1H)8.50(d，J＝7.9Hz，1H)8.61(s，1H)	110-111
69	1H NMR(200MHz，CHLOROFORM-D)d ppm 2.26(s，6H)3.78(s，3H)7.21-7.33(m，1H)7.62-7.72(m，1H)8.28-8.39(m，1H)	182-183

Watch 9 (continuation)

Compound No.	H-NMR	Melting Point (. degree.C.)
			70	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.39(t，J＝7.0Hz，3H)2.26(s，3H)2.26(s，3H)4.30(q，J＝7.0Hz，2H)7.16-7.35(m，1H)7.55-7.76(m，1H)8.14-8.47(m，1H)	198-200
71	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.47-0.61(m，4H)1.22-1.33(m，1H)1.26(t，J＝7.5Hz，3H)2.24(s，3H)2.27(s，3H)3.11(q，J＝7.5Hz，2H)4.14(d，J＝6.8Hz，2H)7.19-7.27(m，2H)7.30-7.37(m，1H)7.97-8.02	150-152
			72	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.53-0.65(m，4H)，1.18-1.41(m，1H)，2.26(s，3H)，2.29(s，3H)，4.21(d，J＝7.0Hz，2H)，7.54(t，J＝7.9Hz，1H)，7.70(d，J＝7.9Hz，1H)，8.44(d，J＝7.9Hz，1H)，8.56(s，1H)	197-199
73	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.46-0.60(m，4H)1.21-1.37(m，1H)2.23(s，3H)2.26(s，3H)2.34(s，3H)2.69(s，3H)4.15(d，J＝7.0Hz，2H)7.02-7.08(m，2H)8.03-8.08(m，1H)	145-148
			74	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.48-0.60(m，4H)，1.22-1.33(m，1H)，2.26(s，3H)，2.28(s，3H)，4.16(d，J＝7.0Hz，2H)，7.18-7.25(m，1H)，7.29-7.38(m，1H)，7.59-7.66(m，1H)，7.87-7.94(m，1H)	125-127
75	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.46-0.62(m，4H)，1.20-1.35(m，1H)，2.25(s，3H)，2.28(s，3H)，4.15(d，J＝6.8Hz，2H)，7.23-7.34(m，2H)，7.37-7.44(m，1H)，7.90-8.00(m，1H)	125-127
			76	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.43-0.58(m，4H)，1.18-1.29(m，1H)，2.25(s，3H)，2.28(s，3H)，4.12(d，J＝7.0Hz，2H)，7.43-7.52(m，1H)，7.52-7.61(m，1H)，7.67-7.74(m，1H)，7.81-7.87(m，1H)	114-116
77	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.52-0.64(m，4H)，1.21-1.36(m，1H)，2.26(s，3H)，2.29(s，3H)，4.20(d，J＝7.0Hz，2H)，7.26-7.35(m，1H)，7.55-7.61(m，1H)，8.17-8.22(m，1H)，8.40-8.43(m，1H)	159-160
			78	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.47-0.62(m，4H)，1.21-1.35(m，1H)，2.25(s，3H)，2.28(s，3H)，4.18(d，J＝6.8Hz，2H)，7.69-7.06(m，1H)，7.33-7.40(m，1H)，7.88-7.99(m，2H)	130-132

Watch 9 (continuation)

Compound No.	H-NMR	Melting Point (. degree.C.)
			79	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.53-0.61(m，4H)，1.22-1.32(m，1H)，2.26(s，3H)，2.29(s，3H)，4.18(d，J＝7.1Hz，2H)7.06-7.16(m，1H)，7.41-7.50(m，1H)，7.94-8.03(m，1H)	109-111
80	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.46-0.62(m，4H)，1.21-1.32(m，1H)，2.26(s，3H)，2.28(s，3H)，4.16(d，J＝7.0Hz，2H)，6.97-7.07(m，1H)，7.32-7.41(m，1H)，7.63-7.72(m，1H)	139-140
			81	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.46-0.61(m，4H)，1.21-1.31(m，1H)，2.26(s，3H)，2.29(s，3H)，4.15(d，J＝7.0Hz，2H)，7.24-7.31(m，1H)，7.41-7.46(m，1H)，7.90-7.97(m，1H)	57-58
82	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.47-0.61(m，4H)，1.14-1.38(m，1H)2.26(s，3H)2.29(s，3H)4.15(d，J＝7.0Hz，2H)7.22-7.37(m，2H)7.90-7.94(m，1H)	113-115
			83	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.52-0.59(m，4H)，1.18-1.32(m，1H)，2.26(s，3H)，2.29(s，3H)，4.17(d，J＝6.8Hz，2H)，7.26-7.35(m，2H)，7.96-8.06(m，1H)	154-155
84	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.48-0.60(m，4H)，1.19-1.34(m，1H)，2.25(s，3H)，2.28(s，3H)，4.16(d，J＝7.0Hz，2H)，6.98-7.11(m，1H)7.32-7.41(m，1H)7.94-8.05(m，1H)	144-146
			85	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.46-0.63(m，4H)1.19-1.33(m，1H)2.26(s，3H)2.29(s，3H)4.16(d，J＝7.0Hz，2H)7.21-7.29(m，1H)7.85-7.94(m，1H)	161-163
86	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.46-0.62(m，4H)，1.26(s，1H)，2.26(s，3H)，2.29(s，3H)，4.15(d，J＝7.0Hz，2H)，7.44-7.51(m，1H)，7.78-7.85(m，1H)	59-60
			87	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.44-0.58(m，4H)，1.14-1.33(m，1H)，2.25(s，3H)，2.28(s，3H)，4.15(d，J＝7.0Hz，2H)，7.28-7.48(m，3H)，8.06(dd，J＝7.5，1.8Hz，1H)
88	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.52-0.60(m，4H)，1.20-1.35(m，1H)，2.24(s，3H)，2.27(s，3H)，3.81(s，3H)，3.87(s，3H)，4.14(d，J＝7.0Hz，2H)，6.88-6.97(m，2H)，7.56-7.61(m，1H)	124-126

Watch 9 (continuation)

Compound No.	H-NMR	Melting Point (. degree.C.)
			89	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.47-0.62(m，4H)，1.20-1.36(m，1H)，2.25(s，3H)，2.28(s，3H)，2.64-2.67(m，3H)，4.16(d，J＝6.9Hz，2H)，6.95-7.05(m，1H)，7.11-7.20(m，1H)，7.77-7.86(m，1H)	82-84
90	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.46-0.61(m，4H)1.20-1.34(m，1H)，2.24(s，3H)，2.28(s，3H)，2.69(s，3H)，4.14(d，J＝6.8Hz，2H)，7.18-7.23(m，2H)，8.03-8.10(m，1H)	124-125
			91	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.47-0.60(m，4H)1.20-1.34(m，1H)2.24(s，3H)2.27(s，3H)2.35(s，3H)4.16(d，J＝7.0Hz，2H)7.11-7.17(m，1H)7.45-7.47(m，1H)7.85-7.90(m，1H)	90-92
92	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.54-0.61(m，4H)，1.20-1.32(m， 1H)，2.27(s，3H)，2.30(s，3H)，4.19(d，J＝7.1Hz，2H)，7.16-7.25(m，1H)，7.62-7.69(m，1H)，8.41-8.48(m，1H)	122-123
			93	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.42-0.59(m，4H)，1.17-1.28(m，1H)，2.26(s，3H)，2.29(s，3H)，4.12(d，J＝7.0Hz，2H)，7.10-7.19(m，1H)，7.51-7.59(m，1H)，7.66-7.74(m，1H)	131-133
94	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.40-0.55(m，4H)，1.13-1.24(m，1H)，2.26(s，3H)，2.28(s，3H)，4.07(d，J＝7.0Hz，2H)，7.23-7.31(m，1H)，7.35-7.48(m，2H)	111-113
			95	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.43-0.59(m，4H)，1.15-1.30(m，1H)，2.26(s，3H)，2.28(s，3H)，4.12(d，J＝7.1Hz，2H)，7.20-7.30(m，1H)，7.37-7.45(m，1H)，7.88-7.97(m，1H)	143-144
96	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.51-0.61(m，4H)，1.20-1.34(m，1H)，2.24(s，3H)，2.27(s，3H)，3.89(s，3H)，4.14(d，J＝7.0Hz，2H)，6.86-6.94(m，1H)，7.02-7.11(m，1H)，7.66-7.74(m，1H)	107-109
			97	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.52-0.59(m，4H)1.19-1.34(m，1H)，2.24(s，3H)，2.27(s，3H)，3.89(s，3H)，4.14(d，J＝7.0Hz，2H)，6.86-6.93(m，1H)，7.27-7.35(m，1H)，7.91-7.96(m，1H)	121-123
98	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.46-0.54(m，4H)，0.87(t，J＝7.5Hz，6H)，1.11-1.22(m，1H)，1.45-1.78(m，4H)，2.19(s，3H)，2.23(s，3H)，2.25-2.35(m，1H)，4.06(d，J＝7.0Hz，2H)	67-69

Watch 9 (continuation)

Compound No.	H-NMR	Melting Point (. degree.C.)
			99	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.48-0.56(m，4H)0.91(s，9H)0.97(d，J＝6.4Hz，3H)1.07-1.37(m，4H)2.19(s，3H)2.21-2.55(m，2H)2.23(s，3H)4.05(d，J＝7.2Hz，2H)	42-43
100	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.45-0.57(m，4H)1.09-1.29(m，4H)1.44-1.68(m，3H)1.74-1.89(m，2H)2.19(s，3H)2.23(s，3H)2.27-2.44(m，1H)2.45-2.52(m，2H)4.04(d，J＝7.0Hz，2H)	108-109
			101	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.51-0.58(m，4H)，1.11-1.22(m，1H)，2.29(s，3H)，2.32(s，3H)，4.13(d，J＝7.0Hz，2H)	92-94
102	1H NMR(300MHz CHLOROFORM-D)d ppm 0.35-0.51(m，4H)0.90(t，J＝7.3Hz，3H)1.01-1.16(m，1H)1.79-2.31(m，2H)2.17(s，3H)2.20(s，3H)3.59(t，J＝7.7Hz，1H)4.00(d，J＝7.2Hz，2H)7.13-7.20(m，1H)7.22-7.30(m，2H)7.33-7.44(m，2H)	108-110
			103	1H NMR(200MHz，CHLOROFORM-D)d ppm 2.25(s，3H)2.28(s，3H)3.33(s，3H)3.81(t，J＝5.3Hz，2H)4.42(t，J＝5.3Hz，2H)7.54(t，J＝7.5Hz，1H)7.71(d，J＝7.5Hz，1H)8.46(d，J＝7.5Hz，1H)8.56(s，1H)	64-66
104	1H NMR(200MHz，CHLOROFORM-D)d ppm 2.25(s，3H)2.28(s，3H)3.31(s，3H)3.79(t，J＝5.3Hz，2H)4.37(t，J＝5.3Hz，2H)7.09-7.38(m，1H)7.53-7.82(m，1H)8.16-8.39(m，1H)	182-183
			105	1H NMR(200MHz，CHLOROFORM-D)d ppm 2.01-2.19(m，2H)，2.26(s，6H)，3.33(s，3H)，3.43(t，J＝5.7Hz，2H)，4.31(t，J＝5.7Hz，2H)，7.20-7.33(m，1H)，7.60-7.75(m，1H)，8.25-8.40(m，1H)	104-106
106	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.15(t，J＝7.0Hz，3H)2.26(s，3H)2.29(s，3H)3.48(d，J＝7.0Hz，2H)3.84(t，J＝5.5Hz，2H)4.42(t，J＝5.5Hz，2H)7.54(t，J＝7.5Hz，1H)7.71(d，J＝7.5Hz，1H)8.46(d，J＝7.5Hz，1	138-140
			107	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.13(t，J＝6.7Hz，3H)2.26(s，3H)2.29(s，3H)3.45(q，J＝6.7Hz，2H)3.82(t，J＝5.3Hz，2H)4.37(t，J＝5.3Hz，2H)7.10-7.37(m，1H)7.51-7.81(m，1H)8.06-8.42(m，1H)	147-148
108	1H NMR(300MHz，CHLOROFORM-D)d ppm 1.25(t，J＝7.6Hz，3H)，1.40(t，J＝7.1Hz，3H)，2.27(s，3H)，2.67(q，J＝7.6，0.5Hz，2H)，4.30(q，J＝7.1Hz，2H)，7.22-7.30(m，1H)，7.63-7.70(m，1H)，8.27-8.35(m，1H)	115-117

Watch 9 (continuation)

Compound No.	H-NMR	Melting Point (. degree.C.)
			109	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.50-0.60(m，4H)，1.18-1.36(m，1H)，1.27(t，J＝7.5Hz，3H)，2.30(s，3H)，2.68(q，J＝7.5Hz，2H)，4.19(d，J＝7.1Hz，2H)，7.27(t，J＝7.0Hz，1H)，7.67(t，J＝7.0Hz，1H)，8.29(t，	164-166
110	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.29(d，J＝6.6Hz，6H)2.27(s，3H)3.08-3.28(m，1H)3.78(s，3H)7.21-7.33(m，1H)7.62-7.72(m，1H)7.21-7.33(m，1H)	89-91
			111	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.29(d，J＝7.0Hz，6H) 1.40(t，J＝7.0Hz，3H)2.28(s，3H)3.02-3.31(m，1H)4.30(q，J＝7.0Hz，2H)7.20-7.32(m，1H)7.67-7.71(m，1H)8.26-8.36(m，1H)	64-66
112	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.69(m，4H)1.09-1.42(m，1H)1.30(d，J＝7.0Hz，6H)2.32(s，3H)3.06-3.31(m，1H)4.22(d，J＝7.0Hz，2H)7.55(t，J＝7.5Hz，1H)7.70(d，J＝7.5Hz，1H)8.44(d，J＝7.5Hz，1H)	89-91
			113	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.63(m，4H)1.15-1.38(m，1H)1.30(d，J＝7.0Hz，6H)2.32(s，3H)3.09-3.27(m，1H)4.19(d，J＝7.0Hz，2H)7.19-7.34(m，1H)7.58-7.73(m，1H)8.20-8.36(m，1H)	64-66
114	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.29(d，J＝7.0Hz，6H)2.30(s，3H)3.07-3.26(m，1H)3.32(s，3H)3.79(t，J＝5.3Hz，2H)4.37(t，J＝5.3Hz，2H)7.20-7.32(m，1H)7.61-7.72(m，1H)8.23-8.34(m，1H)	132-134
			115	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.12(dd，J＝7.0Hz，3H)1.29(d，J＝6.6Hz，6H)2.31(s，3H)3.09-3.26(m，1H)3.45(q，J＝7.0Hz，2H)3.82(t，J＝5.3Hz，2H)4.38(t，J＝5.3Hz，2H)7.20-7.32(m，1H)7.62-7.72（m，1H)8.23-8.34(m，1H)	96-97
116	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.42(s，9H)，2.38(s，3H)2.71(s，3H)，3.75(s，3H)，7.17-7.35(m，3H)，8.08-8.19(m，1H)	173-175
			117	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.39(s，3H)3.71(s，3H)7.40-7.62(m，2H)7.67-7.75(m，1H)7.84-7.92(m，1H)	74-76
118	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)，2.40(s，3H)，3.81(s，3H)，7.43-7.80(m，2H)，8.38-8.68(m，2H)	140-142
			119	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.39(s，3H)3.76(s，3H)7.20-7.36(m，2H)7.37-7.48(m，1H)7.91-8.04(m，1H)	119-121

Watch 9 (continuation)

Compound No.	H-NMR	Melting Point (. degree.C.)
			120	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.39(s，3H)3.76(s，3H)7.15-7.39(m，1H)7.58-7.67(m，1H)7.90-7.99(m，1H)	182-184
121	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.42(s，9H)，2.39(s，3H)，3.79(s，3H)，7.20-7.43(m，1H)，7.54-7.63(m，1H)，8.17-8.29(m，1H)，8.42-8.52(m，1H)	173-175
			122	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(8.9H)2.39(s，3H)3.79(s，3H)6.98-7.10(m，1H)7.31-7.43(m，1H)7.91-7.99(m，2H)	83-85
123	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)，2.39(s，3H)，3.74(s，3H)，7.22-7.51(m，3H)，8.06-8.17(m，1H)
			124	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.42(s，9H)，2.38(s，3H)，3.00(s，6H)，3.79(s，3H)，6.81-6.91(m，1H)，7.24-7.35(m，1H)，7.70-7.80(m，	189-190
125	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.44(s，9H)，2.42(s，3H)，3.82(s，3H)，7.47-7.59(m，1H)，7.67-7.78(m，1H)，8.46-8.55(m，1H)，8.62-8.68(m，1H)	131-133
			126	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.40(s，3H)3.83(s，3H)3.94(s，3H)7.50(t，J＝7.9Hz，1H)8.07-8.21(m，1H)8.44-8.58(m，1H)8.99(t，J＝1.5Hz，1H)	192-193
127	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.44(s，9H)2.41(s，3H)3.84(s，3H)7.55(t，J＝7.9Hz，1H)8.20(d，J＝7.9Hz，1H)8.55(d，J＝7.9Hz，1H)9.07	250-252
			128	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.42(s，9H)，2.40(s，3H)，3.77(s，3H)，7.04-7.28(m，2H)，7.88(t，J＝6.8Hz，1H)	176-178
129	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.40(s，3H)3.78(s，3H)7.05-7.17(m，1H)7.39-7.52(m，1H)7.95-8.07(m，1H)	203-205
			130	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.40(s，3H)3.76(s，3H)6.95-7.09(m，1H)7.31-7.43(m，1H)7.68-7.78(m，1H)	125-126
131	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.40(s，3H)3.76(s，3H)6.88-7.02(m，1H)7.52-7.63(m，1H)7.65-7.75(m，1H)	161-162
			132	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.42(s，9H)2.40(s，3H)3.77(s，3H)6.93-7.06(m，1H)7.43-7.54(m，1H)8.23-8.32(m，1H)	144-145

Watch 9 (continuation)

Compound No.	H-NMR	Melting Point (. degree.C.)
			133	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H) 2.40(s，3H)3.76(s，3H)7.21-7.39(m，2H)7.96-8.01(m，1H)	171-173
134	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.39(s，3H)3.72(s，3H)6.72-6.94(m，1H)6.98-7.21(m，1H)	143-145
			135	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.40(s，3H)3.76(s，3H)7.19-7.31(m，1H)7.88-8.02(m，1H)	145-146
136	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.40(s，3H)3.76(s，3H)7.44-7.51(m，1H)，7.83-7.92(m，1H)	205-207
			137	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.44(s，9H)，2.45(s，3H)，3.46(s，3H)，3.80(s，3H)，3.85(s，3H)，6.46-6.60(m，2H)，7.30(s，1H)	138-140
138	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.40(s，3H)2.66(s，3H)3.76(s，3H)6.92-7.06(m，1H)7.10-7.21(m，1H)7.81-7.92(m，1H)	145-146
			139	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.39(s，3H)2.66(s，3H)3.73(s，3H)7.09-7.20(m，1H)7.35-7.44(m，1H)7.77-7.85(m，1H)	161-162
140	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.39(s，3H)2.68(s，3H)3.73(s，3H)7.01-7.12(m，1H)7.54-7.62(m，1H)7.79-7.87(m，1H)	143-144
			141	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)，2.40(s，3H)，3.78(s，3H)，7.21-7.32(m，1H)，7.66(t，J＝6.4Hz，1H)，8.31(t，J＝6.6Hz，1H)	176-178
142	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)，2.41(s，3H)，3.78(s，3H)，7.15-7.29(m，1H)，7.60-7.70(m，1H)，8.46(dd，J＝6.6，1.8Hz，1H)	140-142
			143	1H NMR(200NHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.40(s，3H)3.72(s，3H)7.05-7.23(m，1H)7.55-7.65(m，1H)7.65-7.76(m，1H)	83-85
144	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.24(s，3H)2.38(s，3H)3.71(s，3H)6.73-6.86(m，1H)6.98-7.20(m，1H)	140-142
			145	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.44(s，9H)2.39(s，3H)3.67(s，3H)7.31-7.64(m，2H)	129-130
146	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.41(s，9H)2.38(s，3H)3.74(s，3H)3.90(s，3H)6.85-6.94(m，1H)7.26-7.36(m，1H)7.96-8.02(m，1H)	177-179
			147	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.41(s，9H)2.38(s，3H)3.74(s，3H)3.91(s，3H)6.89-7.02(m，2H)7.96-8.05(m，1H)	117-119

Watch 9 (continuation)

Compound No.	H-NMR	Melting Point (. degree.C.)
			148	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.46(s，9H)，2.46(s，3H)，3.85(s，3H)，7.92-8.03(m，1H)，8.75(d，J＝5.7Hz，1H)，9.18(d，J＝7.9Hz，1H)，	202-203
149	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.42(s，9H)2.41(s，3H)3.74(s，3H)	180-182
			150	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.28(t，J＝7.7Hz，3H)，1.37(t，J＝7.3Hz，3H)，1.43(s，9H)，2.40(s，3H)，3.14(q，J＝7.7Hz，2H)，4.28(q，J＝7.3Hz，2H)，7.17-7.38(m，3H)，7.98-8.08(m，1H)
151	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.34(t，J＝7.0Hz，3H)1.43(s，9H)2.40(s，3H)4.26(q，J＝7.0Hz，2H)7.40-7.62(m，2H)7.67-7.75(m，1H)7.84-7.92(m，1H)	74-76
			152	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.36-1.52(m，12H)，2.42(s，3H)4.35(q，J＝7.0Hz，2H)，7.38-7.85(m，2H)，8.32-8.70(m，2H)	158-160
153	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.35(t，J＝7.3Hz，3H)1.42(s，9H)2.40(s，3H)4.30(q，J＝7.3Hz，2H)7.23-7.48(m，3H)8.06-8.15(m，1	104-105
			154	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.39(t，J＝7.0Hz，3H)1.42(s，9H)2.41(s，3H)4.31(d，J＝7.0Hz，2H)6.92-7.06(m，1H)7.42-7.54(m，1H)8.20-8.29(m，1H)	105-106
155	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.38(t，J＝7.2Hz，3H)1.43(s，9H)2.41(s，3H)4.30(q，J＝7.2Hz，2H)6.92-7.02(m，1H)7.52-7.63(m，1H)7.63-7.74(m，1H)	115-116
			156	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.38(t，J＝7.0Hz，3H)1.43(s，9H)2.41(s，3H)4.30(q，J＝7.0Hz，2H)6.98-7.11(m，1H)7.32-7.42(m，1H)7.97-8.09(m，1H)	99-100
157	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.39(t，J＝7.2Hz，3H)1.42(s，9H)2.41(s，3H)4.30(q，J＝7.2Hz，2H)6.80-6.94(m，1H)7.60-7.72(m，1H)8.38-8.47(m，1H)	87-89
			158	1H NMR(300MHz，CHLOROFORM-D)d ppm 1.38(t，J＝7.2Hz，3H)1.43(s，9H)2.42(s，3H)4.30(q，J＝7.2Hz，2H)7.23-7.31(m，1H)7.31-7.38(m，1H)7.94-7.99(m，1H)	127-128

Watch 9 (continuation)

Compound No.	H-NMR	Melting Point (. degree.C.)
			159	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.38(t，J＝7.2Hz，3H)1.43(s，9H)2.42(s，3H)4.29(q，J＝7.2Hz，2H)7.16-7.33(m，1H)7.86-8.00(m，1	107-108
160	1H NMR(300MHz，CHLOROFORM-D)d ppm 1.38(t，J＝7.1Hz，3H)1.43(s，9)2.42(s，3H)，4.29(q，J＝7.1Hz，2H)，7.45-7.50(m，1H)，7.83-7.89(m，	112-114
			161	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.39(t，J＝7.0Hz，3H)1.43(s，9H)2.41(s，H)2.67(s，3H)4.30(q，J＝7.0Hz，2H)6.92-7.06(m，1H)7.10-7.21(m，1H)7.80-7.91(m，1H)	108-109
162	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.38(t，J＝7.0Hz，3H)，1.42(s，9H)2.40(s，3H)，2.70(s，3H)，4.29(q，J＝7.0Hz，2H)，7.15-7.24(m，2H)，8.06-8.13(m，1H)	125-126
			163	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.37(t，J＝7.3Hz，3H)1.42(s，9H)2.34(s，3H)，2.40(s，3H)，4.30(q，J＝7.3Hz，2H)，7.09-7.17(m，1H)，7.44-7.49(m，1H)，7.86-7.93(m，1H)	100-102
164	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.34(t，J＝7.2Hz，3H)1.43(s，9H)2.41(s，3H)4.27(q，J＝7.2Hz，2H)7.07-7.21(m，1H)7.54-7.64(m，1H)7.65-7.76(m，1H)	103-104
			165	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.39(t，J＝7.0Hz，3H)1.43(s，9H)2.42(s，3H)4.32(q，J＝7.0Hz，2H)，7.20-7.32(m，1H)7.61-7.72(m，1H)8.25-8.36(m，1H)	97-99
166	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.39(t，J＝7.2Hz，3H)1.42(s，9H)2.41(s，3H)4.30(q，J＝7.2Hz，2H)6.80-6.94(m，1H)7.60-7.72(m，1H)8.38-8.47(m，1H)	113-115
			167	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.37(t，J＝7.3Hz，3H)1.41(s，9H)2.40(s，3H)3.90(s，3H)4.28(q，J＝7.3Hz，2H)6.85-6.94(m，1H)7.26-7.36(m，1H)7.94-7.99(m，1H)	108-109
168	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.37(t，J＝7.0Hz，3H)，1.41(s，9H)2.39(s，3H)，3.91(s，3H)，4.27(q，J＝7.0Hz，2H)，6.91-6.99(m，2H)，7.96-8.03(m，1H)

Watch 9 (continuation)

Compound No.	H-NMR	Melting Point (. degree.C.)
			169	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.42(t，J＝7.2Hz，3H)1.43(s，9H)2.42(s，3H)4.35(q，J＝7.2Hz，2H)7.37(dd，J＝7.9，5.3Hz，1H)8.52(d，J＝7.9Hz，1H)8.67(d，J＝5.3Hz，1H)9.53(s，1H)
170	1H NMR(300MHz，CHLOROFORM-D)d ppm 1.36(t，J＝7.2Hz，3H)1.44(s，9H)2.42(s，3H)4.28(q，J＝7.2Hz，2H)7.59(d，J＝5.3Hz，1H)8.78(d，J＝5.3Hz，1H)9.25(s，1H)	110-112
			171	1H NMR(300MHz，CHLOROFORM-D)d ppm 1.14-1.35(m，2H)1.30(t，J＝7.1H，3H)1.38(s，9H)1.47-1.69(m，4H)1.77-1.90(m，2H)2.31-2.45(m，1H)2.35(s，3H)2.48-2.53(m，2H)4.18(q，J＝7.1Hz，2H)	149-150
172	1H NMR(300MHz，CHLOROFORM-D)d ppm 1.34(t，J＝7.1Hz，3H)，1.42(s，9H)，2.42(s，3H)，4.27(q，J＝7.1Hz，2H)	113-115
			173	1H NMR(200MHz，CHLOROFORM-d)d ppm 1.32-1.46(m，12H)2.42(s，3H)2.76(s，3H)4.30(q，J＝7.3Hz，2H)7.26-7.35(m，1H)7.47-7.57(m，1H)8.37-8.43(m，1H)	63-65
174	1H NMR(200MHz，CHLOROFORM-d)d ppm 1.37(t，J＝7.3Hz，3H)1.43(s，9H)2.41(s，3H)4.29(q，J＝7.3Hz，2H)6.33-7.16(m，2H)7.46-7.56(m，1H)8.17-8.21(m，1H)	95-97
			175	1H NMR(200Hz，CHLOROFORM-D)d ppm 1.06(t.J＝7.5Hz，3H)，1.43(s，9H)，1.73-1.96(m，2H)2.41(s，3H)4.24(t，J＝7.9Hz，2H)，7.54(t，J＝7.7Hz，1H)，7.65-7.77(d，J＝7.7Hz，1H)，8.46(d，J＝7.7Hz，1H)，8.60(s，1	172-174
176	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)，1.78(d，J＝6.6Hz，6H)，2.41(s，3H)，4.48-4.87(m，1H)，7.55(t，J＝7.7Hz，1H)，7.71(d.J＝7.7Hz，1H)，8.46(d，J＝7.7Hz，1H)，8.57(s，1H)	135-137
			177	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.00(d，J＝70Hz，6H)1.44(s，9H)2.23-2.50(m，1H)2.39(s，3H)4.11(d，J＝7.5Hz，2H)7.37(dd，J＝7.9，5.3Hz，1H)8.51(d，J＝7.9Hz，1H)8.67(d，J＝5.3Hz，1H)9.51(s，1H)
178	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.67(m，4H)，1.17-1.36(m，1H)，1.44(s，9H)，2.44(s，3H)，4.24(d，7.0Hz，2H)，7.35-7.49(m，3H)，8.23-8.35(m，2H)	106-107

Watch 9 (continuation)

Compound No.	H-NMR	Melting Point (. degree.C.)
			179	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.56-0.63(m，4H)，1.22-1.29(m，1H)，1.43(s，9H)，2.42(s，3H)，2.44(s，3H)，4.24(d，J＝6.8Hz，2H)，7.27-7.35(m，2H)，8.06-8.13(m，2H)	132-134
180	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.48-0.62(m，4H)，1.19-1.31(m，1H)，1.44(s，9H)，2.43(s，3H)，2.71(s，3H)，4.19(d，J＝6.8Hz，2H)，7.18-7.34(m，3H)，8.05-8.13(m，1H)
			181	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.46-0.62(m，4H)1.10-1.36(m，1H)1.27(t，J＝7.5Hz，3H)1.44(s，9H)2.43(s，3H)3.12(q，J＝7.5Hz，2H)4.17(d，J＝6.6Hz，2H)7.14-7.39(m，3H)7.93-8.01(m，1H)	120-122
182	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.25-0.69(m，4H)1.06-1.34(m，1H)1.27(d，J＝7.0Hz，6H)1.43(s，9H)2.42(s，3H)3.86-4.09(m，1H)4.15(d，J＝7.0Hz，2H)7.08-7.49(m，3H)7.69-7.90(m，1H)	168-169
			183	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.39-0.62(m，4H)1.07-1.31(m，1H)1.43(s，9H)2.42(s，3H)4.13(d，J＝7.0Hz，2H)7.39-7.62(m，2H)7.68(d，J＝7.0Hz，1H)7.82(d，J＝7.0Hz，1H)	90-91
184	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.54-0.64(m，4H)1.16-1.35(m，1H)1.45(s，9H)2.46(s，3H)4.25(d，J＝7.0Hz，2H)7.54(t，J＝7.7Hz，1H)7.70(d，J＝7.7Hz，1H)8.44(d，J＝7.7Hz，1H)8.56(s，1H)	93-94
			185	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.53-0.62(m，4H)，1.18-1.29(m，1H)，1.43(s，9H)，2.44(s，3H)，4.21(d，J＝7.0Hz，2H)，7.04-7.22(m，2H)，7.35-7.43(m，1H)，8.06-8.16(m，J＝7.8，1H)	182-183
186	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.51-0.59(m，4H)，1.17-1.30(m，1H)，1.44(s，9H)，2.44(s，3H)，4.19(d，J＝6.8Hz，2H)，7.26-7.31(m，2H)，7.38-7.45(m，1H)，7.92-7.96(m，1H)
			187	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.55-0.63(m，4H)，1.18-1.34(m，1H)，1.44(s，9H)，2.45(s，3H)，4.23(d，J＝7.0Hz，2H)，7.30-7.46(m，2H)，8.10-8.27(m，2H)
188	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.50-0.63(m，4H)1.16-1.35(m，1H)1.44(s，9H)2.44(s，3H)4.22(d，J＝7.0Hz，2H)7.39(d，J＝8.9Hz，2H)8.21(d，J＝8.9Hz，2H)	94-95

Watch 9 (continuation)

Compound No.	H-NMR	Melting Point (. degree.C.)
			189	1H NMR(300MHz，CHLOROFORM-d)d ppm 0.51-0.58(m，4H)，1.16-1.28(m，1H)，1.44(s，9H)，2.44(s，3H)，4.19(d，J＝7.0Hz，2H)，7.21(t，J＝7.3Hz，1H)，7.33(t，J＝7.3Hz，1H)，7.62(d，J＝7.3Hz，1H)，7.89(d，J＝7.3Hz，1
190	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.50-0.63(m，4H)，1.17-1.34(m，1H)，1.44(s，9H)，2.44(s，3H)，4.19(d，J＝7.0Hz，2H)，7.14-7.38(m，2H)，7.58-7.66(m，1H)，7.85-7.93(m，1H)
			191	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.48-0.61(m，4H)，1.15-1.33(m，1H)，1.44(s，9H)，2.44(s，3H)，4.21(d，J＝7.0Hz，2H)，7.01-7.08(m，1H)，7.24-7.42(m，1H)，7.87-7.99(m，2H)
192	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.53-0.65(m，4H) 1.15-1.36(m，1H)1.44(s，9H)2.45(s，3H)4.23(d，J＝7.0Hz，2H)7.16(t，J＝7.9Hz，1H)7.73-7.81(m，1H)8.18-8.26(m，1H)8.62(t，J＝1.5Hz，1H)	114-115
			193	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.54-0.62(m，4H)，1.20-1.32(m，1H)，1.43(s，9H)，2.43(s，3H)，3.86(s，3H)，4.21(d，J＝6.8Hz，2H)，6.93(d，J＝9.0Hz，2H)，8.24(d，J＝9.0Hz，2H)
194	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.53-0.67(m，4H)，1.17-1.34(m，1H)，1.44(s，9H)，2.44(s，3H)，3.88(s，3H)，4.23(d，J＝7.0Hz，2H)，6.99-7.05(m，1H)，7.30-7.37(m，1H)，7.84-7.92(m，2H)	108-109
			195	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.53-0.61(m，4H)，1.17-1.30(m，1H)，1.42(s，9H)，2.42(s，3H)，3.91(s，3H)，4.17(d，J＝7.0Hz，2H)，6.93-7.01(m，2H)，7.33-7.42(m，1H)，7.96(dd，J＝7.8，1.8Hz，1H)
196	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.55-0.63(m，4H)，1.17-1.31(m，1H)，1.44(s，9H)，2.45(s，3H)，4.23(d，J＝7.0Hz，2H)，7.24-7.32(m，1H)，7.45(t，J＝7.9Hz，1H)，8.12-8.22(m，2H)	106-108
			197	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.48-0.59(m，4H)，1.11-1.33(m，1H)，1.44(s，9H)，2.44(s，3H)，4.18(d，J＝6.6Hz，2H)，7.28-7.49(m，3H)，8.01-8.10(m，1H)
198	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.56-0.63(m，4H)，1.20-1.30(m，1H)，1.44(s，9H)，2.43-2.48(m，3H)，4.24(d，J＝7.0Hz，2H)，5.94(tt，J＝53.2，3.0Hz，1H)，7.26-7.32(m，1H)，7.39-7.48(m，1H)，8.13-8.21	109-111

Watch 9 (continuation)

Compound No.	H-NMR	Melting Point (. degree.C.)
			199	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.36-0.74(m，4H)1.18-1.38(M，1H)1.45(s，9H)2.45(s，3H)4.14(d，J＝6.6Hz，2H)6.66-7.05(m，2H)7.24-7.51(m，1H)8.10-8.19(m，1H)13.16(s，1H)	178-180
200	1H NM(300MHz，CHLOROFORM-D)d ppm 0.52-0.63(m，4H)1.20-1.35(m，1H)1.43(s，9H)2.42(s，3H)2.93(s，3H)4.18(d，J＝6.8Hz，2H)6.57-6.69(m，2H)7.28-7.36(m，1H)8.34(dd，J＝7.9，1.7Hz，1H)8.53-8.70(m，1	158-159
			201	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.55-0.70(m，4H)，1.17-1.35(m，1H)，1.40(s，9H)，2.48(s，3H)，3.22(s，6H)，4.36(d，J＝7.0Hz，2H)，7.57(t，J＝7.9Hz，1H)，8.13(d，J＝7.9Hz，1H)，8.35(d，J＝7.9Hz，1H)，8.54(s，	128-130
202	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.51-0.67(m，4H)1.14-1.31(m，1H)1.19(t，J＝7.1Hz，6H)1.43(s，9H)2.43(s，3H)3.41(q，J＝7.1Hz，4H)4.22(d，J＝7.0Hz，2H)6.79(dd，J＝8.2，2.8Hz，1H)7.26(t，J＝7.6Hz，1H)7.59(d，J＝7.6Hz，1H)7.67-7.73(m，1H)	89-90
			203	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.51-0.64(m，4H)，1.20(t，J＝7.0Hz，6H)，1.14-1.34(m，1H)，1.42(s，9H)，2.41(s，3H)，3.41(q，J＝7.0Hz，4H)，4.19(d，J＝7.0Hz，2H)，6.66(d，J＝9.2Hz，2H)，8.15(d，J＝9.2Hz，2H)	134-136
204	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.51-0.67(m，4H)1.19-1.36(m，1H)1.43(s，9H)1.96-2.09(m，4H)2.43(s，3H)3.29-3.41(m，4H)4.23(d，J＝7.0Hz，2H)6.67(dd，J＝8.1，2.4Hz，1H）7.27(t，J＝8.1Hz，1H)7.52-7.57(m，1H)7.61(d，J＝7.5Hz，1H)	118-120
			205	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.53-0.67(m，4H)1.19-1.36(m，1H)1.44(s，9H)1.50-1.80(m，5H)2.45(s，3H)3.20-3.29(m，4H)4.24(d，J＝7.0Hz，2H)7.07(dd，J＝8.2，2.4Hz，1H)7.31(t，J＝8.2Hz，1H)7.77(d，J＝8.2Hz，1H)7.90-7.96(m，1H)	89-90
206	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.48-0.60(m，4H)1.15-1.33(m，1H)1.44(s，9H)2.43(s，3H)2.99-3.12(m，4H)3.76-3.86(m，4H)4.15(d，J＝6.8Hz，2H)6.92-7.03(m，2H)7.27-7.35(m，1H)7.72(d，J＝7.6Hz，1

Watch 9 (continuation)

Compound No.	H-NMR	Melting Point (. degree.C.)
			207	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.68(m，4H)1.17-1.36(m，1H)1.44(s，9H)2.44(s，3H)3.17-3.30(m，4H)3.83-3.95(m，4H)4.23(d，J＝7.0Hz，2H)7.03(dd，J＝7.9，2.2Hz，1H)7.33(t，J＝7.9Hz，1H)7.82(d，J＝7.5Hz，1H)7.86-7.94(m，1H)	114-115
208	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.50-0.69(m，4H)1.15-1.36(m，1H)1.43(s，9H)2.38(s，3H)2.44(s，3H)2.55-2.71(m，4H)3.21-3.39(m，4H)4.23(d，J＝6.8Hz，2H)7.06(d，J＝7.3Hz，1H)7.32(t，J＝7.3Hz，1H)7.79(d，J＝7.3Hz，1H)7.91(s，1H)	126-128
			209	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.56-0.69(m，4H)1.14-1.38(m，1H)1.45(s，9H)2.47(s，3H)4.28(d，J＝7.0Hz，2H)7.60(t，J＝7.5Hz，1H)8.29(d，J＝7.5Hz，1H)8.57(d，J＝7.5Hz，1H)9.10(s，1H)	87-89
210	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.55-0.66(m，4H)1.09-1.37(m，1H)1.45(s，9H)2.46(s，3H)4.24(d，J＝7.0Hz，2H)7.71(d，J＝8.8Hz，2H)8.35(d，J＝8.8Hz，2H)	125-126
			211	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.39-0.83(m，4H)1.09-1.38(m，1H)1.45(s，9H)2.46(s，3H)4.25(d，J＝7.0Hz，2H)7.54(t，J＝7.7Hz，1H)7.65-7.86(m，1H)8.43-8.59(m，2H)
212	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.47-0.80(m，4H)1.13-1.39(m，1H)1.45(s，9H)2.46(s，3H)4.26(d，J＝6.6Hz，2H)7.53(t，J＝7.7Hz，1H)8.03(d，J＝7.7Hz，1H)8.44(d，J＝7.7Hz，1H)8.63(s，1H)	76-78
			213	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.55-0.64(m，4H)1.16-1.34(m，1H)，1.44(s，9H)，2.46(s，3H)，3.94(s，3H)，4.25(d，J＝7.0Hz，2H)，8.09(d，J＝8.8Hz，2H)，8.32(d，J＝8.8Hz，2H)	122-123
214	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.57-0.65(m，4H)，1.19-1.33(m，1H)，1.45(s，9H)，2.46(s，3H)，4.26(d，J＝7.0Hz，2H)，8.16(d，J＝8.8Hz，2H)，8.36(d，J＝8.8Hz，2H)	196-197
			215	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.51-0.60(m，4H)1.18-1.28(m，1H)，1.44(s，9H)，2.32(s，3H)，2.43(s，3H)，2.51(s，3H)，4.16(d，J＝7.0Hz，2H)，7.07-7.15(m，1H)，7.16-7.21(m，1H)，7.67-7.74(m，1H)	97-98

Watch 9 (continuation)

Compound No.	H-NMR	Melting Point (. degree.C.)
			216	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.54(s，4H)，1.19-1.30(m，1H)，1.43(s，9H)，2.34(s，3H)，2.42(s，3H)，2.69(s，1H)，4.18(d，J＝6.8Hz，2H)，7.00-7.08(m，2H)，8.02-8.06(m，1H)	100-101
217	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.51-0.60(m，4H)，1.17-1.32(m，1H)，1.43(s，9H)，2.35(s，3H)，2.43(s，3H)，2.65(s，3H)，4.19(d，J＝6.8Hz，2H)，7.07-7.14(m，2H)，7.89(s，1H)	106-107
			218	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.38-0.57(m，4H)1.07-1.32(m，1H)1.45(s，9H)2.29(s，6H)2.43(s，3H)4.11(d，J＝6.6Hz，2H)6.95-7.18	98-100
219	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.35-0.75(m，4H)1.02-1.37(m，1H)1.44(s，9H)2.45(s，3H)2.76(s，3H)4.20(d，J＝7.0Hz，2H)7.31(d，J＝7.9Hz，1H)7.52(d，J＝7.9Hz，1H)8.41(s，1H)	91-92
			220	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.30-0.73(m，4H)0.99-1.35(m，1H)1.45(s，9H)2.46(s，3H)4.16(d，J＝7.0Hz，2H)7.72(d，J＝8.4Hz，1H)7.84(d，J＝8.4Hz，1H)8.15(s，1H)	159-161
221	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.50-0.67(m，4H)1.08-1.34(m，1H)1.44(s，9H)2.45(s，3H)4.20(d，J＝7.0Hz，2H)6.98-7.12(m，2H)7.71-7.87(m，1H)	170-172
			222	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.47-0.69(m，4H)1.08-1.36(m，1H)1.44(s，9H)2.45(s，3H)4.21(d，J＝7.0Hz，2H)6.98-7.35(m，2H)7.76-7.93(m，1H)
223	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.44-0.62(m，4H)1.13-1.29(m，1H)，1.44(s，9H)，2.44(s，3H)，4.13(d，J＝6.8Hz，2H)，6.90(t，J＝7.8Hz，2H)，7.20-7.32(m，1H)	123-124
			224	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.53-0.61(m，4H)1.18-1.27(m，1H)，1.43(s，9H)，2.44(s，3H)，4.20(d，J＝7.1Hz，2H)，6.79-6.93(m，2H)，8.09-8.21(m，1H)	111-112
225	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.53-0.63(m，4H)，1.19-1.30(m，1H)，1.44(s，9H)，2.45(s，3H)，4.21(d，J＝7.1Hz，2H)，7.06-7.16(m，1H)，7.40-7.50(m，1H)，7.93-8.02(m，1H)

Watch 9 (continuation)

Compound No.	H-NMR	Melting Point (. degree.C.)
			226	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.53-0.61(m，4H)，1.16-1.29(m，1H)，1.43(s，9H)，2.45(s，3H)，4.20(d，J＝7.0Hz，2H)，7.09-7.21(m，2H)，8.02-8.12(m，1H)	108-110
227	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.52-0.62(m，4H)，1.15-1.30(m，1H)，1.43(s，9H)，2.45(s，3H)，4.20(d，J＝7.1Hz，2H)，7.24-7.35(m，2H)，8.00(t，J＝8.0Hz，1H)	121-131
			228	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.48-0.62(m，4H)，1.17-1.29(m，1H)，1.44(s，9H)，2.45(s，3H)，4.19(d，J＝6.8Hz，2H)，6.89-7.00(m，1H)，7.53-7.67(m，2H)	92-94
229	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.49-0.61(m，4H)，1.18-1.28(m，1H)，1.44(s，9H)，2.44(s，3H)，4.19(d，J＝7.0Hz，2H)，6.09-7.10(m，1H)，7.33-7.40(m，1H)7.94-8.03(m，1H)	126-128
			230	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.54-0.61(m，4H)，1.17-1.28(m，1H)，1.44(s，9H)，2.45(s，3H)，4.20(d，J＝7.0Hz，2H)，6.93-7.04(m，1H)，7.43-7.52(m，1H)，8.19-8.26(m，1H)	113-114
231	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.65(m，4H)，1.06-1.35(m，1)1.44(s，9H)2.45(s，3H)4.20(d，J＝7.0Hz，2H)6.79-6.93(m，1H)7.59-7.74(m，1H)8.36-8.45(m，1H)	95-96
			232	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.48-0.63(m，4H)，1.16-1.29(m，1H)，1.44(s，9H)，2.45(s，3H)，4.19(d，J＝7.0Hz，2H)，7.23-7.28(m，1H)，7.30-7.37(m，1H)，7.90-7.95(m，1H)	129-131
233	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.55-0.63(m，4H)，1.30(s，1H)1.44(s，9H)，2.46(s，3H)，4.23(d，J＝7.0Hz，2H)，7.43(t，J＝1.9Hz，1H)，8.12(d，J＝1.9Hz，2H)
			234	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.64(m，4H)，1.14-1.34(m，1H)1.43(s，9H)2.43(s，3H)3.80(s，3H)3.87(s，3H)4.19(d，J＝6.6Hz，2H)6.86-6.98(m，2H)7.52-7.59(m，1H)	83-85
235	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.49-0.59(m，4H)1.15-1.32(m，1H)1.43(s，9H)2.43(s，3H)3.88(s，3H)3.95(s，1H)4.17(d，J＝6.6Hz，2H)6.96(d，J＝7.5Hz，1H)7.07(t，J＝7.5Hz，1H)7.46(d，J＝7.5Hz，1H)	93-94
			236	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.49-0.62(m，4H)1.19-1.32(m，1H)，1.41(s，9H)，2.41(s，3H)，3.85(s，3H)，3.85(s，3H)，4.16(d，J＝7.9Hz，2H)，6.46-6.56(m，2H)，8.06-8.14(m，1H)

Watch 9 (continuation)

Compound No.	H-NMR	Melting Point (. degree.C.)
			237	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.51-0.59(m，4H)1.17-1.33(m，1H)1.42(s，9H)1.42(t，J＝7.0Hz，3H)1.46(t，J＝7.0Hz，3H)2.40(s，3H)4.07(q，J＝7.0Hz，2H)4.11-4.20(m，4H)6.46-6.51(m，2H)8.02-8.07	116-118
238	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.51-0.57(m，4H)1.17-1.31(m，1H)1.39(t，J＝7.0Hz，6H)1.43(s，9H)2.42(s，3H)4.03(q，J＝7.0Hz，2H)4.11(q，J＝7.0Hz，2H)4.17(d，J＝6.8Hz，2H)6.88-6.91(m.2H)7.47-	97-99
			239	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.50-0.65(m，4H)1.17-1.29(m，1H)，1.43(s，9H)，2.35(s，3H)，2.44(s，3H)，4.21(d，J＝7.0Hz，2H)，6.92-7.02(m，1H)，7.13-7.22(m，1H)，7.85-7.92(m，1H)	117-119
240	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.48-0.62(m，4H)1.16-1.35(m，1H)1.44(s，9H)2.44(s，3H)2.57(d，J＝2.2Hz，3H)4.17(d，J＝7.0Hz，2H)6.98-7.13(m，1H)7.09-7.24(m，1H)7.79(d，J＝7.5Hz，1H)	94-96
			241	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.48-0.64(m，4H)1.18-1.37(m，1H)1.44(s，9H)2.44(s，3H)2.66(s，3H)4.19(d，J＝6.6Hz，2H)6.92-7.06(m，1H)7.09-7.21(m，1H)7.75-7.85(m，1H)	91-93
242	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.47-0.62(m，4H)1.19-1.30(m，1H)，1.44(s，9H)，2.43(s，3H)，2.69(s，3H)，4.18(d，J＝6.8Hz，2H)，7.17-7.23(m，2H)，8.06(d，J＝8.9Hz，1H)	108-109
			243	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.47-0.62(m，4H)1.11-1.34(m，1H)1.44(s，9H)2.44(s，3H)2.65(s，3H)4.16(d，J＝6.6Hz，2H)7.14(t，J＝7.5Hz，1H)7.39(d，J＝7.5Hz，1H)7.76(d，J＝7.5Hz，1H)	88-90
244	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.46-0.54(m，4H)，1.08-1.22(m，1H)，1.45(s，9H)，2.31(s，3H)，2.44(s，3H)，4.11(d，J＝6.8Hz，2H)，7.04-7.24(m，3H)	159-160
			245	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.47-0.69(m，4H)1.16-1.28(m，1H)，1.44(s，9H)，2.44(s，3H)，2.67(s，3H)，4.15(d，J＝6.8Hz，2H)，7.02-7.11(m，1H)，7.54-7.61(m，1H)，7.74-7.81(m，1H)	89-90
246	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.51-0.58(m，4H)1.18-1.30(m，1H)，1.43(s，9H)，2.34(s，3H)，2.43(s，3H)，4.19(d，J＝7.0Hz，2H)，7.10-7.16(m，1H)，7.44-7.48(m，1H)，7.83-7.90(m，1H)	82-84

Watch 9 (continuation)

Compound No.	H-NMR	Melting Point (. degree.C.)
			247	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.50-0.59(m，4H)，1.17-1.27(m，1H)，1.44(s，9H)，2.43(s，3H)，2.46(s，3H)，4.15(d，J＝6.8Hz，2H)，7.17-7.27(m，2H)，7.46-7.53(m，1H)	142-144
248	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.46-0.54(m，4H)，1.10-1.23(m，1H)，1.45(s，9H)，2.31(s，3H)，2.44(s，3H)，4.12(d，J＝6.8Hz，2H)，7.00-7.15(m，2H)，7.34-7.41(m，1H)	89-90
			249	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.48-0.59(m，4H)，1.15-1.29(m，1H)，1.44(s，9H)，2.43(s，3H)，2.51(s，3H)，4.15(d，J＝6.8Hz，2H)，7.20-7.29(m，2H)，7.35-7.42(m，1H)	149-151
250	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.51-0.64(m，4H)1.11-1.33(m，1H)1.44(s，9H)2.46(s，3H)4.21(d，J＝7.0Hz，2H)7.26(t，J＝7.0Hz，1H)7.58-7.72(m，1H)8.20-8.34(m，1H)
			251	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.47-0.67(m，4H)1.08-1.39(m，1H)1.44(s，9H)2.46(s，3H)4.22(d，J＝7.0Hz，2H)7.20(t，J＝8.8Hz，1H)7.56-7.72(m，1H)8.43(dd，J＝6.8，2.4Hz，1H)	113-115
252	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.55-0.63(m，4H)，1.17-1.31(m，1H)，1.44(s，9H)，2.46(s，3H)，4.23(d，J＝7.0Hz，2H)，7.18-7.28(m，1H)，8.40-8.47(m，1H)，8.57(dd，J＝7.3，1.9Hz，1H)	123-124
			253	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.49-0.69(m，4H)，1.17-1.34(m，1H)，1.45(s，9H)，2.47(s，3H)，4.24(d，J＝7.0Hz，2H)，7.36-7.43(m，1H)，8.08-8.15(m，1H)，8.35(s，1H)	100-102
254	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.37-0.70(m，4H)0.99-1.33(m，1H)1.44(s，9H)2.44(s，3H)4.15(d，J＝6.6Hz，2H)7.07-7.20(m，1H)7.48-7.58(m，1H)7.64-7.75(m，1H)	110-112
			255	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.33-0.78(m，4H)0.99-1.35(m，1H)1.42(s，9H)2.42(s，3H)4.13(d，J＝7.0Hz，2H)7.08-7.57(m，2H)7.76-8.02(m，1H)
256	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.42-0.55(m，4H)1.03-1.30(m，1H)1.44(s，9H)2.43(s，3H)4.10(d，J＝7.0Hz，2H)7.19-7.51(m，3H)	128-130

Watch 9 (continuation)

Compound No.	H-NMR	Melting Point (. degree.C.)
			257	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.50-0.64(m，4H)1.16-1.30(m，1H)，1.45(s，9H)，2.46(s，3H)，4.19(d，J＝7.0Hz，2H)，7.49-7.57(m，2H)，8.24-8.27(m，1H)	100-102
258	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.24-0.80(m，4H)1.04-1.34(m，1H)1.45(s，9H)2.45(s，3H)4.15(d，J＝7.0Hz，2H)7.37(t，J＝7.9Hz，1H)7.70(d，J＝7.9Hz，1H)7.88(d，J＝7.9Hz，1H)	93-94
			259	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.51-0.68(m，4H)1.14-1.37(m，1H)1.45(s，9H)2.46(s，3H)4.23(d，J＝7.0Hz，2H)7.51-7.59(m，1H)8.29-8.38(m，1H)8.60-8.65(m，1H)	122-124
260	1H NMR(200MHz，CHLOROFRM-D)d ppm 0.47-0.63(m，4H)0.88(s，9H)1.14-1.45(m，1H)，1.49(s，6H)，1.78(s，2H)，2.45(s，3H)，4.23(d，J＝7.0Hz，2H)，7.20(t，J＝9.2Hz，1H)，7.60-7.71(m，1H)，8.39-8.51(m，	88-89
			261	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.49-0.62(m，4H)1.14-1.38(m，1H)1.43(s，9H)2.42(s，3H)2.74(s，3H)3.84(s，3H)4.18(d，J＝70Hz，2H)6.70-6.82(m，2H)8.16-8.24(m，1H)	95-96
262	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.53-0.60(m，4H)，1.18-1.29(m，1H)，1.43(s，9H)，2.43(s，3H)，3.89(s，3H)，4.17(d，J＝6.8Hz，2H)，6.85-6.94(m，1H)7.00-7.11(m，1H)7.63-7.71(m，1H)	87-89
			263	1H NMR(300MHz，CHOROFORM-D)d ppm 0.46-0.61(m，4H)1.11-1.24(m，1H)，1.43(s，9H)，2.42(s，3H)，3.82(s，3H)，4.11(d，J＝7.1Hz，2H)，6.66-6.74(m，2H)，7.16-7.28(m，1H)	119-121
264	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.51-0.62(m，4H)1.13-1.33(m，1H)1.42(s，9H)2.42(s，3H)3.90(s，3H)4.16(d，J＝7.0Hz，2H)6.89-7.01(m，2H)7.88-7.97(m，1H)	163-165
			265	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.63(m，4H)1.09-1.34(m，1H)1.43(s，9H)2.43(s，3H)3.89(s，3H)4.17(d，J＝6.6Hz，2H)6.84-8.93(m，1H)7.25-7.37(m，1H)7.88-7.94(m，1H)	98-100
266	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.28-0.71(m，4H)1.07-1.34(m，1H)1.44(s，9H)2.44(s，3H)4.17(d，J＝6.6Hz，2H)6.74(t，J＝76.0Hz，1H)7.06-7.14(m，1H)7.46-7.55(m，1H)8.14-8.19(m，1H)	169-170

Watch 9 (continuation)

Compound No.	H-NMR	Melting Point (. degree.C.)
			267	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.48-0.66(m，4H)1.07-1.34(m，1H)1.43(s，9H)2.44(s，3H)3.95(s，3H)4.18(d，J＝7.0Hz，2H)7.02(d，J＝9.2Hz，1H)7.60(d，J＝9.2Hz，1H)8.27(s，1H)	175-177
268	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.50-0.65(m，4H)1.10-1.35(m，1H)1.40-1.53(m，3H)1.44(s，9H)2.44(s，3H)4.11-4.30(m，2H)4.21(d，J＝7.0Hz，2H)7.00(d，J＝8.8Hz，1H)7.56(d，J＝8.8Hz，1H)8.20(s，1H)	140-142
			269	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.48-0.64(m，4H)1.12-1.34(m，1H)1.39(d，J＝6.2Hz，6H)1.43(s，9H)2.43(s，3H)4.15(d，J＝6.6Hz，2H)4.55-4.77(m，1H)7.00(d，J＝8.8Hz，1H)7.55(d，J＝8.8Hz，1H)8.12(s，	106-108
270	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.46-0.66(m，4H)1.06-1.34(m，1H)1.44(s，9H)2.44(s，3H)3.42(s，3H)3.76-3.86(m，2H)4.18(d，J＝6.6Hz，2H)4.22-4.35(m，2H)7.08(d，J＝8.8Hz，1H)7.58(d，J＝8.8Hz，1H)	108-110
			271	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.50-0.66(m，4H)1.13-1.34(m，1H)1.44(s，9H)2.44(s，3H)3.41(s，3H)3.49(t，J＝5.5Hz，2H)3.65(t，J＝5.5Hz，2H)4.20(d，J＝7.0Hz，2H)6.73(d，J＝8.8Hz，1H)7.47(d，J＝8.8Hz，1H)8.61(s，1H)9.09-9.27(m，1H)	131-132
272	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.65(m，4H)1.16-1.36(m，1H)1.44(s，9H)2.44(s，3H)3.49(t，J＝5.5Hz，2H)3.88(t，J＝5.5Hz，2H)4.21(d，J＝6.6Hz，2H)6.77(d，J＝8.8Hz，1H)7.42-7.53(m，1H)8.64(s，	131-133
			273	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.50-0.66(m，4H)1.13-1.34(m，1H)1.44(s，9H)2.44(s，3H)3.41(s，3H)3.49(t，J＝5.5Hz，2H)3.65(t，J＝5.5Hz，2H)4.20(d，7.0Hz，2H)6.73(d，J＝8.8Hz，1H)7.47(d，J＝8.8Hz，1H)8.61(s，1H)9.09-9.27(m，1H)	131-132
274	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.49-0.64(m，4H)1.12(t，J＝7.2Hz，3H)1.18-1.37(m，1H)1.43(s，9H)2.44(s，3H)2.87(s，3H)3.29(q，J＝7.2Hz，2H)4.15(d，J＝7.0Hz，2H)6.90(d，J＝8.4Hz，1H)7.43(d，J＝8.4Hz，1H)7.92(s，1H)	101-103
			275	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.66(m，4H)1.08-1.33(m，1H)1.43(s，9H)2.29(qn，J＝7.5Hz，2H)2.43(s，3H)3.96(t，J＝7.5Hz，4H)4.16(d，J＝6.6Hz，2H)6.48(d，J＝9.2Hz，1H)7.43(d，J＝9.2Hz，1H)7.98	100-102

Watch 9 (continuation)

Compound No.	H-NMR	Melting Point (. degree.C.)
			276	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.48-0.62(m，4H)1.09(t，J＝70Hz，6H)1.15-1.33(m，1H)1.44(s，9H)2.43(s，3H)3.27(q，J＝7.0Hz，4H)4.14(d，J＝7.0Hz，2H)6.94(d，J＝8.4Hz，1H)7.43(d，J＝8.4Hz，1H)7.89	131-133
277	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.51-0.64(m，4H)1.11-1.31(m，1H)1.44(s，9H)2.44(s，3H)2.91(s，6H)4.16(d，J＝7.0Hz，2H)6.90(d，J＝8.8Hz，1H)7.45(dd，J＝8.8，2.0Hz，1H)8.00(d，J＝2.0Hz，1H)	126-128
			278	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.51-0.64(m，4H)，1.10-1.32(m，1H)，1.43(s，9H)，1.83-1.97(m，4H)，2.43(s，3H)，3.22-3.38(m，4H)，4.15(d，J＝6.6Hz，2H)，6.75(d，J＝8.8Hz，1H)，7.41(dd，J＝8.8，2.6Hz，1H)，7.91(d，J＝2.6Hz，1H)
279	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.48-0.62(m，4H)，1.15-1.34(m，1H)，1.44(s，5H)，1.49-1.73(m，6H)，2.43(s，3H)，3.07-3.19(m，4H)4.15(d，J＝7.0Hz，2H)，6.97(d，J＝8.8Hz，1H)，7.45(dd，J＝8.8，2.2Hz，1H)，7.96(d，J＝2.2Hz，1H)	138-140
			280	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.48-0.65(m，4H)，1.09-1.35(m，1H)1.45(s，9H)2.44(s，3H)3.05-3.22(m，4H)3.75-3.91(m，4H)4.16(d，J＝6.6Hz，2H)6.98(d，J＝8.8Hz，1H)7.51(dd，J＝8.8，1.8Hz，1H)8.03(d，	86-87
281	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.43-0.88(m，4H)，1.08-1.39(m，1H)1.45(s，9H)2.46(s，3H)4.23(d，J＝7.0Hz，2H)7.03-7.55(m，1H)8.27-8.77(m，2H)	195-197
			282	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.51-0.64(m，4H)，1.16-1.31(m，1H)，1.44(s，9H)，2.45(s，3H)，4.21(d，J＝7.0Hz，2H)，6.93-7.03(m，1H)，7.83-7.93(m，1H)	82-84
283	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.54-0.60(m，4H)，1.17-1.29(m，1H)，1.43(s，9H)，2.45(s，3H)，4.20(d，J＝7.0Hz，2H)，6.88-7.01(m，1H)7.94-8.03(m，1H)	78-79
			284	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.47-0.63(m，4H)，1.16-1.30(m，1H)，1.44(s，9H)，2.45(s，3H)，4.18(d，J＝7.0Hz，2H)，7.20-7.29(m，1H)，7.83-7.94(m，2H)	112-114

Watch 9 (continuation)

Compound No.	H-NMR	Melting Point (. degree.C.)
			285	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.49-0.67(m，4H)1.08-1.35(m，1H)1.44(s，9H)2.45(s，3H)4.21(d，J＝7.0Hz，2H)6.93-7.07(m，1H)7.94-8.12(m，1H)	76-77
286	1H NMR(300MHz，CHLOROFORM-D)d pmm 0.52-0.60(m，4H)，1.18-1.34(m，1H)，1.43(s，9H)，2.42(s，3H)，3.89(s，3H)，3.90(s，3H)，3.99(s，3H)，4.18(d，J＝6.8Hz，2H)，6.71(d，J＝8.9Hz，1H)，7.78(d，J＝8.9Hz，1H)	88-89
			287	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.50-0.63(m，4H)，1.17-1.28(m，1H)，1.43(s，9H)，2.33(d，J＝2.0Hz，3H)，2.44(s，3H)，4.21(d，J＝7.0Hz，2H)，6.91-6.99(m，1H)，7.71-7.81(m，1H)	122-124
288	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.42-0.69(m，4H)0.94-1.34(m，1H)1.45(s，9H)2.45(s，3H)4.12(d，J＝7.0Hz，2H)6.92-7.05(m，1H)7.40-7.68(m，1H)	109-111
			289	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.37-0.58(m，4H)1.06-1.26(m，1H)1.45(s，9H)2.44(s，3H)4.09(d，J＝7.0Hz，2H)7.34-7.52(m，2H)	182-183
290	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.51-0.67(m，4H)，1.15-1.32(m，1H)，1.45(s，9H)，2.45(s，3H)，4.28(d，J＝7.0Hz，2H)，7.28-7.39(m，1H)，7.72-7.84(m，1H)，8.30(d，J＝7.7Hz，1H)，8.75(d，J＝7.7Hz，1H)
			291	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.59(d，J＝6.6Hz，4H)，1.17-1.38(m，1H)，1.45(s，9H)，2.46(s，3H)，4.24(d，J＝7.0Hz，2H)，7.30-7.43(m，1H)，8.43-8.55(m，1H)，8.63-8.71(m，1H)，9.46-9.52(m，1H)
292	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.53-0.64(m，4H)，1.18-1.31(m，1H)，1.46(s，9H)，2.47(s，3H)，4.26(d，J＝7.0Hz，2H)，8.58-8.64(m，1H)，8.68-8.74(m，1H)，9.49-9.54(m，1H)
			293	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.48-0.56(m，4H)，1.10-1.28(m，1H)，1.44(s，9H)，2.43(s，3H)，2.54(s，3H)，4.19(d，J＝6.8Hz，2H)，7.16-7.22(m，1H)，7.51-7.55(m，1H)，8.46-8.51(m，1H)	88-89
294	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.64(d，4H)，1.08-1.38(m，1H)，1.44(s，9H)，2.42(s，3H)，2.46(s，3H)，4.24(d，J＝7.0Hz，2H)，7.31-7.47(m，1H)，7.67-7.94(m，1H)，8.35-8.50(m，1H)

Watch 9 (continuation)

Compound No.	H-NMR	Melting Point (. degree.C.)
			295	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.42-0.66(m，4H)，1.14-1.34(m，1H)，1.44(s，9H)，2.45(s，3H)，2.97(s，3H)，4.18(d，J＝6.6Hz，2H)，7.24-7.46(m，1H)，7.64-7.93(m，1H)，8.41-8.55(m，1H)
296	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.52-0.62(m，4H)1.16-1.31(m，1H)1.44(s，9H) 2.45(s，3H)2.62(s，3H)4.22(d，J＝7.0Hz，2H)7.22(d，J＝7.9Hz，1H) 8.38(dd，J＝7.9，2.2Hz，1H)9.38(d，J＝2.2Hz，1H)	228-230
			297	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.49-0.67(m，4H)，1.15-1.33(m，1H)，1.29(t，J＝7.6Hz，3H)，1.44(s，9H)，2.45(s，3H)，2.73(d，J＝7.6Hz，2H)，4.29(d，J＝7.0Hz，2H)，7.18(d，J＝5.0Hz，1H)，8.15(s，1H)，8.62	104-106
298	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.43-0.62(m，4H)1.05-1.35(m，1H)1.45(s，9H)2.45(s，3H)4.16(d，J＝7.0Hz，2H)7.58(d，J＝4.8Hz，1H)8.77(d，J＝4.8Hz，1H)9.20(s，1H)	74-76
			299	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.40-0.58(m，4H)，1.07-1.29(m，1H)，1.46(s，9H)，2.29(s，3H)，2.45(s，3H)，2.52(s，3H)，4.11(d，J＝6.8Hz，2H)，6.96(d，J＝5.1Hz，1H)，8.31(d，J＝5.1Hz，1H)	156-157
300	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.50-0.66(m，4H)，1.09-1.38(m，1H)，1.44(s，9H)，2.46(s，3H)，4.24(d，J＝22.0Hz，2H)，7.20-7.34(m，1H)，8.21-8.32(m，1H)，8.45-8.59(m，1H)	83-84
			301	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.49-0.63(m，4H)1.10-1.34(m，1H)1.45(s，9H)2.45(s，3H)4.20(d，J＝7.0Hz，2H)7.28(dd，J＝7.5，4.8Hz，1H)8.25(dd，J＝7.5，2.2Hz，1H)8.41(dd，J＝4.8，2.2Hz，1H)	124-125
302	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.46-0.65(m，4H)1.14-1.35(m，1H)1.44(s，H)2.45(s，3H)4.20(d，J＝7.0Hz，2H)7.36(d，J＝5.3Hz，1H)8.47(d，J＝5.3Hz，1H)9.21(s，1H)
			303	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.67(m，4H)1.13-1.37(m，1H)1.45(s，9H)2.46(s，3H)4.23(d，J＝6.6Hz，2H) 8.60(dd，J＝2.6，1.3Hz，1H)8.73(d，J＝2.6Hz，1H)9.36(d，J＝1.3Hz，1H)	152-154

Watch 9 (continuation)

Compound No.	H-NMR	Melting Point (. degree.C.)
			304	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.46-0.58(m，4H)1.08-1.34(m，1H)1.45(s，9H)2.44(s，3H)4.19(d，J＝7.0Hz，2H)7.17(dd，J＝7.9，4.8Hz，1H)7.93(d，J＝7.9Hz，1H)8.58(d，J＝4.8Hz，1H)	141-142
305	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.47-0.61(m，4H)1.09-1.34(m，1H)1.45(s，9H)2.46(s，3H)4.17(d，J＝7.0Hz，2H)8.37(d，J＝2.6Hz，1H)8.52(d，J＝2.6Hz，1H)	115-116
			306	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.48-0.61(m，4H)1.06-1.31(m，1H)1.44(s，9H)2.44(s，3H)4.15(d，J＝7.0Hz，2H)7.26(d，J＝8.4Hz，1H)7.67(d，J＝8.4Hz，1H)	143-145
307	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.44-0.66(m，4H)1.07-1.37(m，1H)1.45(s，9H)2.47(s，3H)4.19(d，J＝7.0Hz，2H)7.77(s，1H)8.41(s，1	110-112
			308	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.40-0.64(m，4H)0.98-1.32(m，1H)1.46(s，9H)2.46(s，3H)4.11(d，J＝7.0Hz，2H)8.48(s，2H)	260-261
309	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.48-0.64(m，4H)，1.17-1.29(m，1H)，1.45(s，9H)，2.47(s，3H)，4.20(d，J＝6.8Hz，2H)，8.23(d，J＝2.6Hz，1H)，8.36(d，J＝2.6Hz，1H)	113-134
			310	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.49-0.63(m，4H)1.15-1.34(m，1H)1.43(s，9H)1.44(t，J＝7.0Hz，3H)2.43(s，3H)4.18(d，J＝7.0Hz，2H)4.53(q，J＝7.0Hz，2H)6.90(dd，J＝7.5，4.8Hz，1H)8.19(dd，J＝4.8，2.2Hz，1H)8.28(dd，J＝7.5，2.2Hz，1H)	102-104
311	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.49-0.60(m，4H)，1.22-1.35(m，1H)，1.40(d，J＝6.2Hz，6H)，1.43(s，9H)，2.42(s，3H)，4.17(d，J＝7.0Hz，2H)，5.35-5.55(m，1H)，6.80-6.92(m，1H)，8.13-8.26 (m，2H)	151-153
			312	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.53-0.61(m，4H)，1.20-1.31(m，1H)，1.43(s，9H)，2.45(s，3H)，2.52(s，3H)，4.29(d，J＝6.8Hz，2H)，7.01-7.10(m，1H)，8.46-8.53(m，2H)	138-139

Watch 9 (continuation)

Compound No.	H-NMR	Melting Point (. degree.C.)
			313	1H NMR(200MHz，CHLOROFORM-D)d ppm 5.11-5.22(m，4H)5.82-6.07(m，1H)6.16(s，9H)7.15(s，3H)8.85(d，J＝7.0Hz，2H)11.79(dd，J＝7.5，4.8Hz，1H)11.83-11.96(m，3H)12.04-12.19(m，2H)12.92(dd，J＝4.8，2.2Hz，1H)13.14(dd，J＝7.5，2.2Hz，1H)	111-114
314	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.48-0.66(m，4H)1.07-1.33(m，1H)1.43(s，9H)2.45(s，3H)4.08(s，3H)4.14(s，3H)4.16(d，J＝6.6Hz，2H)7.39(s，1H)	124-126
			315	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.49-0.63(m，4H)，1.14-1.31(m，1H)，1.43(s，9H)，1.82-1.94(m，4H)，2.43(s，3H)，3.38-3.51(m，4H)，4.13(d，J＝6.6Hz，2H)，6.58(dd，J＝7.5，4.8Hz，1H)，7.89(dd，J＝7.5，2.2Hz，1H)，8.17(dd，J＝4.8，2.2Hz，2H)	97-98
316	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.34-0.78(m，4H)1.03-1.38(m，1H)1.44(s，9H)2.45(s，3H)2.89(s，3H)4.18(d，J＝7.0Hz，2H)6.73-6.81(m，1H)8.45-8.57(m，1H)	67-69
			317	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.66(m，4H)，1.12-1.34(m，1H)，1.44(s，9H)，2.46(s，3H)，3.98(s，3H)，4.22(d，J＝7.0Hz，2H)，7.43(d，J＝0.9Hz，1H)，7.65(d，J＝0.9Hz，1H)	127-128
318	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.53-0.60(m，4H)，0.85(t，J＝7.3Hz，3H)，1.20-1.31(m，1H)，1.43(s，9H)，1.52-1.70(m，2H)，2.42(s，3H)，3.07-3.16(m，2H)，4.17(d，J＝6.8Hz，2H)，7.39-7.54(m，5H)，8.18	104-105
			319	1H MHR(200MHz，CHLOROFORM-D)d ppm 0.54-0.70(m，4H)1.07-1.31(m，1H)1.44(s，9H)2.47(s，3H)4.21(d，J＝7.0Hz，2H)7.19(d，J＝4.0Hz，1H)7.33(d，J＝4.0Hz，1H)	129-130
320	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.55-0.68(m，4H)1.16-1.39(m，1H)1.46(s，9H)2.48(s，3H)4.27(d，J＝7.0Hz，2H)7.84(d，J＝9.7Hz，1H)8.33(d，J＝9.7Hz，1H)8.77(s，1H)	139-141

Watch 9 (continuation)

Compound No.	H-NMR	Melting Point (. degree.C.)
			321	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.49-0.71(m，4H)1.17-1.40(m，1H)1.47(s，9H)2.47(s，3H)4.25(d，J＝7.0Hz，2H)7.65(dd，J＝8.1，7.3Hz，1H)8.05(d，J＝8.1Hz，1H)8.56(d，J＝6.2Hz，1H)8.62(dd，J＝7.3，1.5Hz，1H)9.14(d，J＝6.2Hz，1H)9.26(s，1H)	109-110
322	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.46-0.67(m，4H)1.03-1.38(m，1H)1.45(s，9H)2.44(s，3H)4.15(d，J＝7.0Hz，2H)7.38(dd，J＝8.1，4.2Hz，1H)7.56(dd，J＝8.1，7.0Hz，1H)7.84(dd，J＝8.1，1.8Hz，1H)8.06(dd，J＝7.0，1.8Hz，1H)8.15(dd，J＝8.1，2.0Hz，1H)9.04(dd，J＝4.2，2.0Hz，1	193-195
			323	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.47-0.68(m，4H)1.12-1.39(m，1H)1.47(s，9H)2.48(s，3H)4.23(d，J＝7.0Hz，2H)7.57(ddd，J＝8.4，6.8，1.5Hz，1H)7.71(ddd，J＝8.4，6.8，1.5Hz，1H)8.01(d，J＝4.4Hz，1H)8.13(d，J＝7.5Hz，1H)9.00(d，J＝4.4Hz，1H)9.05(dd，J＝7.5，1.1Hz，1H)	124-126
324	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.47-0.54(m，4H)，1.12-1.24(m，1H)，1.48(s，9H)，2.46(s，3H)，4.22(d，J＝7.9Hz，2H)，7.52-7.87(m，4H)，8.56-8.72(m，2H)
			325	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.43-0.75(m，4H)，1.15-1.41(m，1H)，1.50(s，9H)，2.54(s，3H)，4.13-4.50(m，2H)，8.02-8.27(m，2H)，8.72-8.92(m，1H)，9.54-9.75(m，1H)，9.90-10.21(m，1H)	140-141
326	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.46-0.72(m，4H)1.12-1.38(m，1H)1.48(s，9H)2.49(s，3H)4.23(d，J＝7.0Hz，2H)7.57(t，J＝8.4Hz，1H)7.72(t，J＝8.4Hz，1H)7.98(s，1H)8.04(d，J＝8.4Hz，1H)9.00(d，J＝8.4	201-203
			327	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.38-0.59(m，4H)1.01-1.28(m，1H)1.46(s，9H)2.44(s，3H)4.10(d，J＝7.0Hz，2H)7.56(d，J＝9.2Hz，1H)7.65(d，J＝9.2Hz，1H)8.09(d，J＝2.6Hz，1H)8.80(d，J＝2.6Hz，1H)	172-174
328	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.36-0.65(m，4H)1.06-1.36(m，1H)1.46(s，9H)2.46(s，3H)4.18(d，J＝7.0Hz，2H)7.69(d，J＝5.3Hz，1H)7.92(d，J＝5.3Hz，1H)8.69(s，1H)	147-149
			329	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.38(s，9H)2.07(s，3H)3.15(t，J＝7.0Hz，2H)4.46(t，J＝7.0Hz，2H)7.10-7.19(m，2H)7.22-7.36(m，3H)7.40(dd，J＝7.9，4.8Hz，1H)8.56(d，J＝7.9Hz，1H)8.69(d，J＝4.8Hz，1
330	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.45-0.61(m，4H)1.02-1.22(m，1H)1.24(s，9H)1.39(s，9H)2.39(s，3H)4.10(d，J＝7.0Hz，2H)	102-104

Watch 9 (continuation)

Compound No.	H-NMR	Melting Point (. degree.C.)
			331	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.49-0.60(m，4H)，1.09-1.20(m，1H)，1.39(s，9H)，1.83-2.02(m，2H)，2.12-2.42(m，4H)，2.39(s，1H)，3.22-3.35(m，1H)，4.08(d，J＝6.8Hz，2H)	189-191
332	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.39-0.65(m，4H)1.02-2.07(m，12H)1.39(s，9H)2.38(s，3H)4.08(d，J＝7.0Hz，2H)	141-142
			333	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.64(m，4H)，1.07-1.36(m，1H)，1.44(s，9H)，2.47(s，3H)，4.15(d，J＝7.0Hz，2H)
334	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.49-0.63(m，4H)1.05-1.29(m，1H)1.43(s，9H)2.46(s，3H)4.14(d，J＝7.0Hz，2H)6.21(tt，J＝53.2，5.7Hz，	93-94
			335	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.46-0.60(m，4H)，1.08-1.22(m，1H)，1.41(s，9H)，2.41(s，3H)，2.47-2.64(m，2H)，2.68-2.76(m，2H)，4.08(m，J＝6.8Hz，2H)	102-103
336	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.53-0.59(m，4H)，1.08-1.20(m，1H)，1.43(s，9H)，2.47(s，3H)，4.15(d，J＝7.0Hz，2H)	147-148
			337	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.46-0.59(m，4H)1.05-1.36(m，2H)1.37(s，9H)1.60-1.74(m，1H)2.07-2.20(m，1H)2.38(s，3H)2.49-2.65(m，1H)4.07(d，J＝6.6Hz，2H)7.08-7.32(m，5H)	110-112
338	1H NMR(300MHz，CHLOROFORM-D)d ppm 1.42(s，9H)，2.44(s，3H)，3.29(s，3H)，3.70(t，J＝5.2Hz，2H)，4.34(t，J＝5.1Hz，2H)	69-71
			339	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.35-0.51(m，4H)，1.01-1.16(m，1H)，1.37(s，9H)，2.36(s，3H)，3.76(s，2H)，4.01(d，J＝7.0Hz，2H)，7.14-7.22(m，1H)，7.22-7.38(m，4H)	92-94
340	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.43-0.54(m，4H)，1.04-1.18(m，1H)，1.38(s，9H)，2.38(s，3H)，3.97(s，2H)，4.07(d，J＝7.0Hz，2H)，6.91-6.94(m，2H)，7.13-7.17(m，1H)	157-159
			341	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.21-0.54(m，4H)，0.87-1.08(m，1H)，1.36(s，9H)，2.22(s，3H)，2.35(s，3H)，3.92(dd，J＝14.2，6.5Hz，1H)，4.08(dd，J＝14.2，7.5Hz，1H)，6.14(s，1H)，7.23-7.36(m，3H)，7.50	147-148

Watch 9 (continuation)

Compound No.	H-NMR	Melting Point (. degree.C.)
			342	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.32-0.47(m，4H)，0.99-1.10(m，1H)，1.37(s，9H)，2.36(s，3H)，3.75(s，6H)，3.78(s，2H)，3.96(d，J＝7.0Hz，2H)，6.69-6.88(m，3H)	89-91
343	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.42(s，9H)，2.37(s，3H)，4.92-5.00(m，2H)，5.02-5.30(m，2H)，5.89-6.11(m，1H)，7.35-7.47(m，3H)，8.26-8.35(m，2H)
			344	1H NMR(200MHz，CHLOROFFORM-D)d ppm 1.44(s，9H)2.44(s，3H)3.34(m，2H)3.81(t，J＝5.5Hz，2H)4.44(t，J＝5.5Hz，2H)7.54(t，J＝7.5Hz，3H)7.71(d，J＝7.5Hz，1H)8.45(d，J＝7.5Hz，1H)8.56(s，1H)	172-173
345	1H NMR(300MHz，CHLOROFORM-D)d ppm 1.43(s，9H)，2.44(s，3H)，3.34(s，3H)，3.81(t，J＝5.4Hz，2H)，4.42(t，J＝5.4Hz，2H)，7.26-7.33(m，1H)，7.55-7.61(m，1H)，8.18-8.23(m，1H)，8.40-8.44(m，1H)	89-91
			346	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.43(s，3H)3.34(s，3H)3.80(t，J＝5.5Hz，2H)4.41(t，J＝5.5Hz，2H)7.16(t，J＝7.9Hz，1H)7.78(d，J＝7.9Hz，1H)8.23(d，J＝7.9Hz，1H)8.62(s，1H)	119-121
347	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.42(s，9H)，2.42(s，3H)，3.31(s，3H)，3.77(t，J＝5.5Hz，2H)，4.37(t，J＝5.5Hz，2H)，7.07-7.21(m，2H)，8.02-8.14(m，1H)	68-69
			348	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)，2.43(s，3H)，3.32(s，3H)，3.78(t，J＝5.3Hz，2H)，4.38(t，J＝5.3Hz，2H)，6.92-7.04(m，1H)，7.43-7.53(m，1H)，8.18-8.26(m，1H)	95-97
349	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.44(s，3H)3.31(s，3H)3.75(t，J＝5.3Hz，2H)4.37(t，J＝5.3Hz，2H)7.43-7.51(m，1H)7.78-	161-163
			350	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.43(s，3H)3.34(s，3H)3.80(t，J＝5.5Hz，2H)4.42(t，J＝5.5Hz，2H)5.39-6.34(m，1H)7.18-7.36(m，1H)7.38-7.50(m，1H)8.01-8.32(m，2H)	114-116
351	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.43(s，3H)2.66(s，3H)3.32(s，3H)3.77(t，J＝5.5Hz，2H)4.37(t，J＝5.5Hz，2H)6.91-7.07(m，1H)7.08-7.23(m，1H)7.72-7.90(m，1H)	106-107

Watch 9 (continuation)

Compound No.	H-NMR	Melting Point (. degree.C.)
			352	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.14(t，J＝7.0Hz，3H)1.43(s，9H)2.46(s，3H)3.47(d，J＝7.0Hz，2H)3.84(t，J＝5.5Hz，2H)4.44(t，J＝5.5Hz，2H)7.54(t，J＝7.7Hz，1H)7.71(d，J＝7.7Hz，1H)8.46(d，J＝7.7Hz，1	91-92
353	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.43(s，9H)2.42(s，3H)3.93(s，1H)4.08(t，J＝5.3Hz，2H)4.48(t，J＝5.3Hz，2H)7.55(t，J＝7.9Hz，1H)7.72(d，J＝7.9Hz，1H)8.42(d，J＝7.9Hz，1H)8.51(s，1H)	147-149
			354	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.44(s，9H)2.45(s，3H)3.19(t，J＝6.4Hz，2H)4.37(t，J＝6.4Hz，2H)7.55(t，J＝7.7Hz，1H)7.71(d，J＝7.7Hz，1H)8.46(d，J＝7.7Hz，1H)8.56(s，1H)	76-78
355	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.42(s，9H)2.16-2.33(m，2H)3.82-3.93(m，2H)4.32-4.44(m，2H)7.37-7.50(m，1H)7.63-7.77(m，3H)7.79-7.88(m，2H)8.35-8.44(m，1H)8.51-8.55(m，1H)	129-130
			356	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.53-0.71(m，4H)1.16-1.45(m，1H)1.37(t，J＝7.0Hz，3H)2.79(s，3H)4.34(q，J＝7.0Hz，2H)4.30(d，J＝7.9Hz，2H)7.58(t，J＝7.7Hz，1H)7.75(d，J＝7.7Hz，1H)8.45(d，J＝7.7Hz，1	115-116
357	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.63-1.01(m，4H)1.16-1.41(m，1H)2.34-2.73(m，3H)3.53-3.87(m，2H)7.01-7.24(m，1H)7.30-7.59(m，1H)7.91-8.29(m，2H)	291-293
			358	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.71(m，4H)1.17-1.43(m，1H)1.25(d，J＝6.6Hz，6H)2.78(s，3H)4.10-4.35(m，1H)4.29(d，J＝7.0Hz，2H)5.47-5.65(m，1H)7.58(t，J＝7.7Hz，1H)7.76(d，J＝7.7Hz，1H)8.44(d，J＝7.7Hz，1H)8.55(s，1H)	212-214
359	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.54-0.70(m，4H)1.17-1.45(m，1H)2.49(s，3H)3.13(s，6H)4.25(d，J＝7.0Hz，2H)7.57(t，J＝7.7Hz，1H)7.74(d，J＝7.7Hz，1H)8.44(d，J＝7.7Hz，1H)8.56(s，1H)	138-140
			360	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.54-0.71(m，4H)1.19-1.45(m，1H)1.89-2.06(m，4H)2.59(s，3H)3.53-3.74(m，4H)4.27(d，J＝7.0Hz，2H)7.57(t，J＝7.7Hz，1H)7.74(d，J＝7.7Hz，1H)8.44(d，J＝7.7Hz，1H)	125-127

Watch 9 (continuation)

Compound No.	H-NMR	Melting Point (. degree.C.)
			361	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.54-0.71(m，4H)1.14-1.46(m，1H)2.43-2.57(m，4H)2.58(t，J＝6.2Hz，2H)2.78(s，3H)3.51(q，J＝6.2Hz，2H)3.67-3.83(m，4H)4.30(d，J＝7.0Hz，2H)6.31-6.49(m，1H)7.59(t，J＝7.7Hz，1H)7.76(d，J＝7.7Hz，1H)8.45(d，J＝7.7Hz，1H)8.55(s，1	156-158
362	1H NMR(200MHz，CHLOROFORM-d)d ppm 1.35(6H，d，J＝5.27Hz)，3.47-3.72(1H，m)，3.67(3H，s)，7.84-7.95(1H，m)，8.52-8.61(1H，m)，8.79-8.86(1H，m)，9.49-9.58(1H，m)
			363	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.63(m，2H)，0.81-0.96(m，2H)，1.21-1.51(m，1H)，1.36(d，J＝7.0Hz，6H)，3.45-3.67(m，1H)，4.41(d，J＝7.5Hz，2H)，8.25(s，1H)，9.18(s，1H)，9.43(s，1H)	139-141
364	1H NMR(300MHz，CHLOROFORM-D)d ppm 1.42(t，J＝7.1Hz，3H)，2.36(s，3H)4.33(q，J＝7.0Hz，2H)，7.24-7.33(m，1H)，7.66-7.74(m，1H)，8.27-	158-160
			365	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.49-0.67(m，4H)1.20-1.38(m，1H)2.39(s，3H)4.21(d，J＝7.0Hz，2H)7.29(t，J＝7.7Hz，1H)7.70(t，J＝7.7Hz，1H) 8.29(t，J＝7.7Hz，1H)	130-132
366	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.13-0.48(m，4H)，0.98-1.18(m，1H)，2.15(s，3H)，4.07(d，J＝7.0Hz，2H)，7.27-7.41(m，2H)，7.47-7.63(m，4H)，7.72(d，J＝7.5Hz，1H)，8.48(d，J＝7.5Hz，1H)，8.59(s，1H)	161-162
			367	1H NMR(200MHz，CHLOROFORM-D)d ppm 2.04(s，3H)，2.22(s，3H)，2.65(s，3H)，4.39-4.47(m，2H)，5.10-5.30(m，2H)，5.79-6.01(m，1H)，7.11-7.33(m，3H)，7.96-8.05(m，1H)
368	1H NMR(200MHz，CHLOROFORM-D)d ppm 4.66-4.83(m，2H)，4.89-5.26(m，2H)，5.86-6.07(m，1H)，7.10-7.56(m，13H)，8.31-8.42(m，2H)	141-143
			369	1H NMR(600MHz，CHLOROFORM-d)d ppm 0.43-0.48(m，2H)0.56-0.61(m，2H)1.13-1.20(m，1H)1.26(d，J＝7.3Hz，6H)2.13(s，3H)2.90-2.96(m，1H)3.70(d，J＝7.3Hz，2H)7.21-7.25(m，1H)7.61-7.65(m，1H)8.17-
370	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.42-0.68(m，4H)1.14-1.36(m，1H)1.31(d，J＝7.0Hz，6H)2.14(s，3H)2.86-3.05(m，1H)3.74(d，J＝7.0Hz，2H)7.44-7.57(m，1H)7.64-7.73(m，1H)8.37-8.44(m，1H)8.47-	65-67

Watch 9 (continuation)

Compound No.	H-NMR	Melting Point (. degree.C.)
			371	1H NMR(300MHz，CHLOROFORM-d)d ppm 0.43-0.64(m，4H)1.08-1.24(m，1H)1.29(d，J＝7.0Hz，6H)2.14(s，3H)2.86-3.00(m，1H)3.71(d，J＝7.1Hz，2H)7.10-7.22(m，1H)7.57-7.68(m，1H)8.30-8.39(m，1H)	76-78
372	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.41-0.65(m，4H)1.09-1.31(m，1H)1.20(d，J＝7.0Hz，6H)2.11(s，3H)2.80-2.97(m，1H)3.68(d，J＝7.0Hz，2H)3.90(s，3H)6.93-7.01(m，1H)7.53-7.61(m，1H)8.03-8.07	118-120
			373	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.50-0.65(m，4H)1.35-1.54(m，1H)2.75(s，3H)4.42(d，J＝7.0Hz，2H)7.20-7.54(m，6H)7.70(d，J＝7.0Hz，1H)8.21(d，J＝7.9Hz，1H)	115-117
374	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.74(m，4H)，1.33-1.55(m，1H)，3.03(s，6H)，4.45(d，J＝7.0Hz，2H)，6.86-6.97(m，1H)，7.25-7.51(m，4H)，7.67-7.80(m，3H)	156-158
			375	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.66(m，4H)，1.34-1.53(m，1H)，2.98(s，3H)，4.43(d，J＝7.5Hz，2H)，7.18-7.57(m，4H)，7.73(d，J＝7.0Hz，1H)，8.42-8.51(m，1H)，8.54-8.62(m，1H)	181-183
376	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.53-0.65(m，4H)1.34-1.52(m，1H)2.36(s，3H)2.41(s，3H)2.74(s，3H)4.38(d，J＝7.0Hz，2H)7.17-7.42(m，3H)7.19(s，1H)7.45(s，1H)8.19(d，J＝7.9Hz，1H)	160-161
			377	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.55-0.65(m，4H)，1.32-1.50(m，1H)，2.74(s，3H)，4.39(d，J＝7.0Hz，2H)，7.12-7.46(m，6H)，8.17-8.25	143-145
378	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.50-0.59(m，2H)，0.62-0.72(m，2H)，1.45-1.61(m，1H)，2.75(s，3H)，4.98(d，J＝7.1Hz，2H)，7.17-7.48(m，5H)，7.60(d，J＝7.6Hz，1H)，8.22(d，J＝7.8Hz，1H)	146-148
			379	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.49-0.69(m，4H)，1.19-1.35(m，1H)，2.74(s，3H)，2.86(s，3H)，4.78(d，J＝6.5Hz，2H)，7.15-7.40(m，5H)，7.51-7.59(m，1H)，8.19(d，J＝6.2Hz，1H)	133-134
380	1H NMR(300MHz，CHLOROFORM-D)d ppm 0.50-0.65(m，4H)，1.40-1.52(m，1H)，2.74(s，3H)，4.57(d，J＝8.5Hz，2H)，6.92-7.03(m，1H)，7.19-7.43(m，4H)，8.22(d，J＝7.5Hz，1H)	146-148

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Compound No.	H-NMR	Melting Point (. degree.C.)
			381	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.52-0.65(m，4H)1.18-1.42(m，1H)1.79-2.04(m，4H)2.56-2.70(m，4H)4.15(d，J＝7.0Hz，2H)7.55(t，J＝7.7Hz，1H)7.71(d，J＝7.7Hz，1H)8.46(d，J＝7.7Hz，1H)8.57(s，1H)	159-160
382	1H NMR(200MHz，CHLOROFORM-d)d ppm 0.56-0.69(m，4H)1.28-1.50(m，1H)4.42(d，J＝7.5Hz，2H)7.24-7.47(m，2H)7.62-7.82(m，2H)8.29-8.42(m，1H)8.49-8.57(m，1H)	156-158

Watch 10

Compound No.	Melting Point (. degree.C.) or NMR
		383	178.5-180.5
384	141.5-142.5
		385	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.35(s，9H)，2.25(s，3H)，3.43(s，3H)，7.38-7.52(m，3H)，7.94-8.02(m，2H)
386	173-174.5
		387	190-192
388	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.29-0.51(m，4H)，0.89-1.12(m，1H)，1.36(s，9H)，2.29(s，3H)，3.84(d，J＝7.0Hz，2H)，7.37-7.54(m，3H)，7.91-8.01(m，2H)
		389	198-199.5
390	121-124
		391	122-123
392	125-127
		393	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.29-0.54(m，4H)，0.99-1.19(m，1H)，1.36(s，9H)，2.31(s，3H)，3.85(d，J＝6.6Hz，2H)，7.29-7.50(m，3H)，8.15-8.26(m，1H)
394	126-128
		395	159-160
396	140.5-141.5
		397	132-134
398	100-102
		399	104-105
400	130-131

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Compound No.	Melting Point (. degree.C.) or NMR
		401	149-151
402	132-135
		403	110-112
404	150-152
		405	69-72
406	127-129
		407	124-126
408	126.5-128
		409	136-138
410	136-138
		411	129-131
412	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.31-0.53(m，4H)，0.94-1.11(m，1H)，1.36(s，9H)，2.30(s，3H)，3.84(d，J＝7.0Hz，2H)，7.11-7.23(m，1H)，7.31-7.44(m，2H)，7.87-7.95(m，2H)
		413	132.5-134
414	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.29-0.58(m，4H)，0.96-1.13(m，1H)，1.36(s，9H)，2.30(s，3H)，2.67(s，3H)，7.00-7.12(m，1H)，7.16-7.27(m，1H)，7.74-7.84
		415
416
		417	124-125.5

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Compound No.	Melting Point (. degree.C.) or NMR
		418	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.30-0.44(m，4H)，0.90-1.11(m，1H)，1.38(s，9H)，2.37(s，3H)，3.80(s，3H)，3.84(d，J＝7.0Hz，2H)，6.70-6.84(m，2H)，7.87-
419	158-160
		420	97-99
421	86-88
		422	145.5-147
423	146-147.5
		424	85-87
425	145-146
		426	156-158.5
427	207.5-208.5
		428	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.35(s，9H)，2.15(s，3H)，5.21(s，2H)，7.10-7.18(m，1H)，7.23-7.57(m，6H)，7.84-7.92(m，2H)
429	94-95
		430	186.5-188
431	273-274.5
		432	139-142
433	171-173
		434	1H NMR(200MHz，CHLOROFORM-D)d ppm 1.20(t，J＝7.3Hz，3H)，1.36(s，9H)，2.18(s，3H)，4.13(q，J＝7.0Hz，2H)，4.68(s，2H)，7.36-7.53(m，3H)，7.88-7.95(m，2H)
435	163.5-165

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Compound No.	Melting Point (. degree.C.) or NMR
		436	103-104
437	75-79
		438	194-195
439	68-69
		440	111-112
441	74-78
		442	1H NMR(200MHz，CHLOROFORM-D)d ppm 0.19-0.43(m，4H)，0.91-1.12(m，1H)，2.14(s，3H)，2.74(t，J＝6.2Hz，4H)，3.77(t，J＝6.2Hz，2H)，3.80(d，J＝7.0Hz，2H)，7.45-7.66(m，3H)，7.82-8.01(m，2H)，8.28-3.38(m，2H)，8.85-8.93(m，1H)
443	135-136.5
		444	144-146
445	170-172
		446	1H NMR(200MHz，CHLOROFORM-D)d ppm 4.63-4.75(m，2H)，5.05-5.27(m，2H)，5.65-5.96(m，1H)，7.10-7.64(m，8H)，7.88-8.06(m，2H)
447	174-175.5

TABLE 11

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TABLE 12

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Compound No.	MASS
		1151	APCI(Pos)297(M+H)
1152	APCI(Pos)297(M+H)
		1153	APCI(Pos)339(M+H)
1154	APCI(Pos)351(M+H)
		1155	APCI(Pos)301(M+H)
1156	APCI(Pos)301(M+H)
		1157	APCI(Pos)301(M+H)
1158	APCI(Pos)317(M+H)
		1159	APCI(Pos)317(M+H)
1160	APCI(Pos)317(M+H)
		1161	APCI(Pos)351(M+H)
1162	APCI(Pos)397(M+H)
		1163	APCI(Pos)400(M+H)
1164	APCI(Pos)286(M+H)
		1165	APCI(Pos)296(M+H)
1166	APCI(Pos)306(M+H)
		1167	APCI(Pos)295(M+H)
1168	APCI(Pos)295(M+H)
		1169	APCI(Pos)307(M+H)
1170	APCI(Pos)307(M+H)
		1171	APCI(Pos)307(M+H)
1172	APCI(Pos)307(M+H)
		1173	APCI(Pos)307(M+H)
1174	APCI(Pos)323(M+H)
		1175	APCI(Pos)323(M+H)

Compound No.	MASS
		1176	APCI(Pos)323(M+H)
1177	APCI(Pos)323(M+H)
		1178	APCI(Pos)323(M+H)
1179	APCI(Pos)339(M+H)
		1180	APCI(Pos)355(M+H)
1181	APCI(Pos)355(M+H)
		1182	APCI(Pos)387(M+H)
1183	APCI(Pos)343(M+H)
		1184	APCI(Pos)343(M+H)
1185	ESI(Pos)343(M+H)
		1186	APCI(Pos)311(M+H)
1187	APCI(Pos)303(M+H)
		1188	APCI(Pos)303(M+H)
1189	APCI(Pos)319(M+H)
		1190	APCI(Pos)319(M+H)
1191	APCI(Pos)357(M+H)
		1192	APCI(Pos)357(M+H)
1193	APCI(Pos)373(M+H)
		1194	APCI(Pos)373(M+H)
1195	APCI(Pos)327(M+H)
		1196	APCI(Pos)337(M+H)
1197	APCI(Pos)339(M+H)
		1198	APCI(Pos)247(M+H)
1199	APCI(Pos)311(M+H)
		1200	APCI(Pos)323(M+H)

Compound No.	MASS
		1201	APCI(Pos)333(M+H)
1202	APCI(Pos)311(M+H)
		1203	APCI(Pos)311(M+H)
1204	APCI(Pos)325(M+H)
		1205	APCI(Pos)295(M+H)
1206	APCI(Pos)311(M+H)
		1207	APCI(Pos)263(M+H)
1208	APCI(Pos)264(M+H)
		1209	APCI(Pos)279(M+H)
1210	APCI(Pos)322(M+H)
		1211	APCI(Pos)322(M+H)
1212	APCI(Pos)322(M+H)
		1213	APCI(Pos)289(M+H)
1214	APCI(Pos)304(M+H)
		1215	APCI(Pos)304(M+H)
1216	APCI(Pos)304(M+H)
		1217	APCI(Pos)304(M+H)
1218	APCI(Pos)304(M+H)
		1219	APCI(Pos)338(M+H)
1220	APCI(Pos)375(M+H)

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Compound No.	MASS
		1221	APCI(Pos)310(M+H)
1222	APCI(Pos)310(M+H)
		1223	APCI(Pos)311(M+H)
1224	APCI(Pos)311(M+H)
		1225	APCI(Pos)327(M+H)
1226	APCI(Pos)327(M+H)
		1227	APCI(Pos)311(M+H)
1228	APCI(Pos)311(M+H)
		1229	APCI(Pos)311(M+H)
1230	APCI(Pos)311(M+H)
		1231	APCI(Pos)312(M+H)
1232	APCI(Pos)328(M+H)
		1233	APCI(Pos)329(M+H)
1234	ESI(Neg)322(M+H)
		1235	APCI(Pos)355(M+H)
1236	APCI(Pos)389(M+H)
		1237	APCI(Pos)437(M+H)
1238	APCI(Pos)358(M+H)
		1239	APCI(Pos)471(M+H)
1240	APCI(Pos)325(M+H)
		1241	APCI(Pos)325(M+H)
1242	APCI(Pos)325(M+H)
		1243	APCI(Pos)368(M+H)
1244	APCI(Pos)394(M+H)

Compound No.	MASS
		1245	APCI(Pos)396(M+H)
1246	APCI(Pos)408(M+H)
		1247	APCI(Pos)408(M+H)
1248	APCI(Pos)410(M+H)
		1249	APCI(Pos)410(M+H)
1250	APCI(Pos)368(M+H)
		1251	APCI(Pos)387(M+H)
1252	APCI(Pos)401(M+H)
		1253	APCI(Pos)417(M+H)
1254	APCI(Pos)417(M+H)
		1255	APCI(Pos)421(M+H)
1256	APCI(Pos)432(M+H)
		1257	APCI(Pos)432(M+H)
1258	APCI(Pos)446(M+H)
		1259	APCI(Pos)341(M+H)
1260	APCI(Pos)341(M+H)
		1261	APCI(Pos)341(M+H)
1262	APCI(Pos)355(M+H)
		1263	APCI(Pos)383(M+H)
1264	APCI(Pos)392(M+H)
		1265	APCI(Pos)403(M+H)
1266	APCI(Pos)404(M+H)
		1267	APCI(Pos)409(M+H)
1268	APCI(Pos)424(M+H)

Compound No.	MASS
		1269	APCI(Pos)369(M+H)
1270	APCI(Pos)405(M+H)
		1271	APCI(Pos)361(M+H)
1272	APCI(Pos)361(M+H)
		1273	APCI(Pos)405(M+H)
1274	APCI(Pos)405(M+H)
		1275	APCI(Pos)405(M+H)
1276	APCI(Pos)372(M+H)
		1277	APCI(Pos)384(M+H)
1278	APCI(Pos)371(M+H)
		1279	APCI(Pos)357(M+H)
1280	APCI(Pos)405(M+H)
		1281	APCI(Pos)325(M+H)
1282	APCI(Pos)325(M+H)
		1283	APCI(Pos)325(M+H)
1284	APCI(Pos)325(M+H)
		1285	APCI(Pos)325(M+H)
1286	APCI(Pos)339(M+H)
		1287	APCI(Pos)339(M+H)
1288	APCI(Pos)339(M+H)
		1289	APCI(Pos)387(M+H)
1290	APCI(Pos)387(M+H)
		1291	APCI(Pos)405(M+H)
1292	APCI(Pos)417(M+H)

Watch 12 (continuation)

Compound No.	MASS
		1293	APCI(Pos)345(M+H)
1294	APCI(Pos)356(M+H)
		1295	APCI(Pos)356(M+H)
1296	APCI(Pos)388(M+H)
		1297	APCI(Pos)388(M+H)
1298	APCI(Pos)388(M+H)
		1299	APCI(Pos)326(M+H)
1300	APCI(Pos)326(M+H)
		1301	APCI(Pos)326(M+H)
1302	APCI(Pos)342(M+H)
		1303	APCI(Pos)342(M+H)
1304	APCI(Pos)405(M+H)
		1305	APCI(Pos)405(M+H)
1306	APCI(Pos)410(M+H)
		1307	APCI(Pos)418(M+H)
1308	APCI(Pos)438(M+H)
		1309	APCI(Pos)404(M+H)
1310	APCI(Pos)343(M+H)
		1311	APCI(Pos)405(M+H)
1312	APCI(Pos)419(M+H)
		1313	APCI(Pos)415(M+H)
1314	APCI(Pos)431(M+H)
		1315	APCI(Pos)489(M+H)
1316	APCI(Pos)339(M+H)

Compound No.	MASS
		1317	APCI(Pos)339(M+H)
1318	APCI(Pos)381(M+H)
		1319	APCI(Pos)393(M+H)
1320	APCI(Pos)424(M+H)
		1321	APCI(Pos)419(M+H)
1322	APCI(Pos)515(M+H)
		1323	APCI(Pos)391(M+H)
1324	APCI(Pos)435(M+H)
		1325	APCI(Pos)439(M+H)
1326	APCI(Pos)448(M+H)
		1327	APCI(Pos)463(M+H)
1328	APCI(Pos)489(M+H)
		1329	APCI(Pos)500(M+H)
1330	APCI(Pos)339(M+H)
		1321	APCI(Pos)339(M+H)
1332	APCI(Pos)339(M+H)
		1333	APCI(Pos)353(M+H)
1334	APCI(Pos)353(M+H)
		1335	APCI(Pos)353(M+H)
1336	APCI(Pos)353(M+H)
		1337	APCI(Pos)353(M+H)
1338	APCI(Pos)367(M+H)
		1339	APCI(Pos)367(M+H)
1340	APCI(Pos)367(M+H)

Compound No.	MASS
		1341	APCI(Pos)381(M+H)
1342	APCI(Pos)393(M+H)
		1343	APCI(Pos)393(M+H)
1344	APCI(Pos)393(M+H)
		1345	APCI(Pos)457(M+H)
1346	APCI(Pos)525(M+H)
		1347	APCI(Pos)415(M+H)
1348	APCI(Pos)401(M+H)
		1349	APCI(Pos)401(M+H)
1350	APCI(Pos)415(M+H)
		1351	APCI(Pos)419(M+H)
1352	APCI(Pos)429(M+H)
		1353	APCI(Pos)455(M+H)
1354	APCI(Pos)339(M+H)
		1355	APCI(Pos)359(M+H)
1356	APCI(Pos)359(M+H)
		1357	APCI(Pos)359(M+H)
1358	APCI(Pos)373(M+H)
		1359	APCI(Pos)373(M+H)
1360	APCI(Pos)403(M+H)
		1361	APCI(Pos)403(M+H)
1362	APCI(Pos)417(M+H)
		1363	APCI(Pos)340(M+H)
1364	APCI(Pos)340(M+H)

Watch 12 (continuation)

Compound No.	MASS
		1365	APCI(Pos)384(M+H)
1366	APCI(Pos)402(M+H)
		1367	APCI(Pos)402(M+H)
1368	APCI(Pos)420(M+H)
		1369	APCI(Pos)436(M+H)
1370	APCI(Pos)454(M+H)
		1371	APCI(Pos)470(M+H)
1372	APCI(Pos)419(M+H)
		1373	APCI(Pos)419(M+H)
1374	APCI(Pos)420(M+H)
		1375	APCI(Pos)460(M+H)
1376	APCI(Pos)356(M+H)
		1377	APCI(Pos)410(M+H)
1378	APCI(Pos)396(M+H)
		1379	APCI(Pos)402(M+H)
1380	APCI(Pos)340(M+H)
		1381	APCI(Pos)429(M+H)
1382	APCI(Pos)378(M+H)
		1383	APCI(Pos)434(M+H)
1384	APCI(Pos)448(M+H)
		1385	APCI(Pos)380(M+H)
1386	APCI(Pos)413(M+H)
		1387	APCI(Pos)467(M+H)
1388	APCI(Pos)429(M+H)

Compound No.	MASS
		1389	APCI(Pos)353(M+H)
1390	APCI(Pos)373(M+H)
		1391	APCI(Pos)387(M+H)
1392	APCI(Pos)417(M+H)
		1393	APCI(Pos)417(M+H)
1394	APCI(Pos)427(M+H)
		1395	APCI(Pos)431(M+H)
1396	APCI(Pos)373(M+H)
		1397	APCI(Pos)374(M+H)
1398	APCI(Pos)374(M+H)
		1399	APCI(Pos)374(M+H)
1400	APCI(Pos)388(M+H)
		1401	APCI(Pos)390(M+H)
1402	APCI(Pos)376(M+H)
		1403	APCI(Pos)378(M+H)
1404	APCI(Pos)390(M+H)
		1405	APCI(Pos)444(M+H)
1406	APCI(Pos)405(M+H)
		1407	APCI(Pos)420(M+H)
1408	APCI(Pos)361(M+H)
		1409	APCI(Pos)361(M+H)
1410	APCI(Pos)361(M+H)
		1411	APCI(Pos)375(M+H)
1412	APCI(Pos)395(M+H)

Compound No.	MASS
		1413	APCI(Pos)396(M+H)
1414	APCI(Pos)390(M+H)
		1415	APCI(Pos)444(M+H)
1416	APCI(Pos)427(M+H)
		1417	APCI(Pos)381(M+H)
1418	APCI(Pos)361(M+H)
		1419	APCI(Pos)375(M+H)
1420	APCI(Pos)391(M+H)
		1421	APCI(Pos)405(M+H)
1422	APCI(Pos)379(M+H)
		1423	APCI(Pos)367(M+H)
1424	APCI(Pos)381(M+H)
		1425	APCI(Pos)377(M+H)
1426	APCI(Pos)377(M+H)
		1427	APCI(Pos)391(M+H)
1428	APCI(Pos)411(M+H)
		1429	APCI(Pos)425(M+H)
1430	APCI(Pos)383(M+H)
		1431	APCI(Pos)362(M+H)

Watch 13

Compound No.	MASS
		2001	APCI：267(M+H)+
2002	APCI：267(M+H)+
		2003	APCI：293(M+H)+
2004	APCI：297(M+H)+
		2005	APCI：301(M+H)+
2006	APCI：301(M+H)+
		2007	APCI：302(M+H)+
2008	APCI：302(M+H)+
		2009	APCI：305(M+H)+
2010	APCI：306(M+H)+
		2011	APCI：307(M+H)+
2012	APCI：307(M+H)+
		2013	APCI：312(M+H)+
2014	APCI：315(M+H)+
		2015	APCI：315(M+H)+
2016	APCI：315(M+H)+
		2017	APCI：316(M+H)+
2018	APCI：317(M+H)+
		2019	APCI：319(M+H)+
2020	APCI：319(M+H)+
		2021	APCI：321(M+H)+
2022	APCI：322(M+H)+
		2023	APCI：323(M+H)+
2024	APCI：323(M+H)+
		2025	APCI：323(M+H)+
2026	APCI：323(M+H)+
		2027	APCI：323(M+H)+
2028	APCI：327(M+H)+
		2029	APCI：330(M+H)+
2030	APCI：331(M+H)+
		2031	APCI：331(M+H)+
2032	APCI：332(M+H)+
		2033	APCI：333(M+H)+
2034	APCI：335(M+H)+
		2035	APCI：335(M+H)+
2036	APCI：337(M+H)+
		2037	APCI：337(M+H)+
2038	APCI：337(M+H)+
		2039	APCI：338(M+H)+
2040	APCI：338(M+H)+

Compound No.	MASS
		2041	APCI：338(M+H)+
2042	APCI：338(M+H)+
		2043	APCI：339(M+H)+
2044	APCI：339(M+H)+
		2045	APCI：339(M+H)+
2046	APCI：339(M+H)+
		2047	APCI：341(M+H)+
2048	APCI：341(M+H)+
		2049	APCI：341(M+H)+
2050	APCI：347(M+H)+
		2051	APCI：347(M+H)+
2052	APCI：351(M+H)+
		2053	APCI：353(M+H)+
2054	APCI：353(M+H)+
		2055	APCI：355(M+H)+
2056	APCI：355(M+H)+
		2057	APCI：355(M+H)+
2058	APCI：356(M+H)+
		2059	APCI：356(M+H)+
2060	APCI：356(M+H)+
		2061	APCI：356(M+H)+
2062	APCI：357(M+H)+
		2063	APCI：366(M+H)+
2064	APCI：366(M+H)+
		2065	APCI：369(M+H)+
2066	APCI：371(M+H)+
		2067	APCI：372(M+H)+
2068	APCI：372(M+H)+
		2069	APCI：373(M+H)+
2070	APCI：375(M+H)+
		2071	APCI：375(M+H)+
2072	APCI：379(M+H)+
		2073	APCI：379(M+H)+
2074	APCI：379(M+H)+
		2075	APCI：383(M+H)+
2076	APCI：383(M+H)+
		2077	APCI：389(M+H)+
2078	APCI：395(M+H)+
		2079	APCI：403(M+H)+
2080	APCI：406(M+H)+

Watch 13 (continue)

The No is combined.	MASS
		2081	APCI：407(M+H)+
2082	APCI：412(M+H)+
		2083	APCI：413(M+H)+
2084	APCI：427(M+H)+
		2085	APCI：431(M+H)+
2086	APCI：269(M+H)+
		2087	APCI：269(M+H)+
2088	APCI：283(M+H)+
		2089	APCI：295(M+H)+
2090	APCI：295(M+H)+
		2091	APCI：299(M+H)+
2092	APCI：304(M+H)+
		2092	APCI：304(M+H)+
2094	APCI：304(M+H)+
		2095	APCI：307(M+H)+
2096	APCI：308(M+H)+
		2097	APCI：309(M+H)+
2098	APCI：309(M+H)+
		2099	APCI：317(M+H)+
2100	APCI：317(M+H)+
		2101	APCI：317(M+H)+
2102	APCI：317(M+H)+
		2103	APCI：317(M+H)+
2104	APCI：318(M+H)+
		2105	APCI：319(M+H)+
2106	APCI：321(M+H)+
		2107	APCI：321(M+H)+
2108	APCI：323(M+H)+
		2109	APCI：324(M+H)+
2110	APCI：325(M+H)+
		2111	APCI：325(M+H)+
2112	APCI：325(M+H)+
		2113	APCI：325(M+H)+
2114	APCI：325(M+H)+
		2115	APCI：329(M+H)+
2116	APCI：331(M+H)+
		2117	APCI：333(N+H)+
2118	APCI：333(M+H)+
		2119	APCI：334(M+H)+
2120	APCI：335(M+H)+

Compound No.	MASS
		2121	APCI：337(M+H)+
2122	APCI：337(M+H)+
		2123	APCI：337(M+H)+
2124	APCI：339(M+H)+
		2125	APCI：339(M+H)+
2126	APCI：340(M+H)+
		2127	APCI：340(M+H)+
2128	APCI：340(M+H)+
		2129	APCI：340(M+H)+
2130	APCI：341(M+H)+
		2131	APCI：341(M+H)+
2132	APCI：341(M+H)+
		2133	APCI：341(M+H)+
2134	APCI：343(M+H)+
		2135	APCI：343(M+H)+
2136	APCI：349(M+H)+
		2137	APCI：349(M+H)+
2138	APCI：355(M+H)+
		2139	APCI：355(M+H)+
2140	APCI：357(M+H)+
		2141	APCI：357(M+H)+
2142	APCI：357(M+H)+
		2143	APCI：358(M+H)+
2144	APCI：358(M+H)+
		2145	APCI：358(M+H)+
2146	APCI：358(M+H)+
		2147	APCI：358(M+H)+
2148	APCI：359(M+H)+
		2149	APCI：368(M+H)+
2150	APCI：368(M+H)+
		2151	APCI：371(M+H)+
2152	APCI：373(M+H)+
		2153	APCI：374(M+H)+
2154	APCI：375(M+H)+
		2155	APCI：375(M+H)+
2156	APCI：377(M+H)+
		2157	APCI：377(M+H)+
2158	APCI：379(M+H)+
		2159	APCI：381(M+H)+
2160	APCI：381(M+H)+

Watch 13 (continue)

Compound No.	MASS
		2161	APCI：381(M+H)+
2162	APCI：385(M+H)+
		2163	APCI：385(M+H)+
2164	APCI：391(M+H)+
		2165	APCI：397(M+H)+
2166	APCI：405(M+H)+
		2167	APCI：408(M+H)+
2168	APCI：414(M+H)+
		2169	APCI：415(M+H)+
2170	APCI：429(M+H)+
		2171	APCI：433(M+H)+
2172	APCI：283(M+H)+
		2173	APCI：283(M+H)+
2174	APCI：297(M+H)+
		2175	APCI：309(M+H)+
2176	APCI：313(M+H)+
		2177	APCI：317(M+H)+
2178	APCI：317(M+H)+
		2179	APCI：318(M+H)+
2180	APCI：318(M+H)+
		2181	APCI：321(M+H)+
2182	APCI：322(M+H)+
		2183	APCI：323(M+H)+
2184	APCI：323(M+H)+
		2185	APCI：328(M+H)+
2186	APCI：331(M+H)+
		2187	APCI：331(M+H)+
2188	APCI：331(M+H)+
		2189	APCI：331(M+H)+
2190	APCI：332(M+H)+
		2191	APCI：333(M+H)+
2192	APCI：335(M+H)+
		2193	APCI：335(M+H)+
2194	APCI：337(M+H)+
		2195	APCI；337(M+H)+
2196	APCI：338(M+H)+
		2197	APCI：339(M+H)+
2198	APCI：339(M+H)+
		2199	APCI：339(M+H)+
2200	APCI：339(M+H)+

Compound No.	MASS
		2201	APCI：339(M+H)+
2202	APCI：339(M+H)+
		2203	APCI：343(M+H)+
2204	APCI：345(M+H)+
		2205	APCI：346(M+H)+
2206	APCI：347(M+H)+
		2207	APCI：347(M+H)+
2208	APCI：348(M+H)+
		2209	APCI：349(M+H)+
2210	APCI：351(M+H)+
		2211	APCI：351(M+H)+
2212	APCI：353(M+H)+
		2213	APCI：353(M+H)+
2214	APCI：353(M+H)+
		2215	APCI：354(M+H)+
2216	APCI：354(M+H)+
		2217	APCI：354(M+H)+
2218	APCI：354(M+H)+
		2219	APCI：355(M+H)+
2220	APCI：355(M+H)+
		2221	APCI：355(M+H)+
2222	APCI：355(M+H)+
		2223	APCI：355(M+H)+
2224	APCI：355(M+H)+
		2225	APCI：357(M+H)+
2226	APCI：357(M+H)+
		2227	APCI：357(M+H)+
2228	APCI：363(M+H)+
		2229	APCI：363(M+H)+
2230	APCI：363(M+H)+
		2231	APCI：369(M+H)+
2232	APCI：369(M+H)+
		2233	APCI：371(M+H)+
2234	APCI：371(M+H)+
		2235	APCI：371(M+H)+
2236	APCI：372(M+H)+
		2237	APCI：372(M+H)+
2238	APCI：372(M+H)+
		2239	APCI：372(M+H)+
2240	APCI：373(M+H)+

Watch 13 (continue)

Compound No.	MASS
		2241	APCI：381(M+H)+
2242	APCI：381(M+H)+
		2243	APCI：382(M+H)+
2244	APCI：382(M+H)+
		2245	APCI：385(M+H)+
2246	APCI：387(M+H)+
		2247	APCI：388(M+H)+
2248	APCI：388(M+H)+
		2249	APCI：389(M+H)+
2250	APCI：389(M+H)+
		2251	APCI：389(M+H)+
2252	APCI：391(M+H)+
		2253	APCI：391(M+H)+
2254	APCI：393(M+H)+
		2255	APCI：395(M+H)+
2256	APCI：395(M+H)+
		2257	APCI：395(M+H)+
2258	APCI：399(M+H)+
		2259	APCI：405(M+H)+
2260	APCI：411(M+H)+
		2261	APCI：419(M+H)+
2262	APCI：429(M+H)+
		2263	APCI：428(M+H)+
2264	APCI：429(M+H)+
		2265	APCI：429(M+H)+
2266	APCI：443(M+H)+
		2267	APCI：313(M+H)+
2268	APCI：313(M+H)+
		2269	APCI：327(M+H)+
2270	APCI：339(M+H)+
		2271	APCI：339(M+H)+
2272	APCI：343(M+H)+
		2273	APCI：347(M+H)+
2274	APCI：347(M+H)+
		2275	APCI：348(M+H)+
2276	APCI：348(M+H)+
		2277	APCI：351(M+H)+
2278	APCI：352(M+H)+
		2279	APCI：353(M+H)+
2280	APCI：353(M+H)+

Compound No.	MASS
		2281	APCI：358(M+H)+
2282	APCI：361(M+H)+
		2283	APCI：361(M+H)+
2284	APCI：361(M+H)+
		2285	APCI：361(M+H)+
2286	APCI：361(M+H)+
		2287	APCI：362(M+H)+
2288	APCI：363(M+H)+
		2289	APCI：365(M+H)+
2290	APCI：365(M+H)+
		2291	APCI：367(M+H)+
2292	APCI：367(M+H)+
		2293	APCI：368(M+H)+
2294	APCI：369(M+H)+
		2295	APCI：369(M+H)+
2296	APCI：369(M+H)+
		2297	APCI：369(M+H)+
2298	APCI：369(M+H)+
		2299	APCI：369(M+H)+
2300	APCI：373(M+H)+
		2301	APCI：375(M+H)+
2302	APCI：376(M+H)+
		2303	APCI：377(M+H)+
2304	APCI：377(M+H)+
		2305	APCI：378(M+H)+
2306	APCI：379(M+H)+
		2307	APCI：381(M+H)+
2308	APCI：381(M+H)+
		2309	APCI：381(M+H)+
2310	APCI：381(M+H)+
		2311	APCI：383(M+H)+
2312	APCI：383(M+H)+
		2313	APCI：383(M+H)+
2314	APCI：384(M+H)+
		2315	APCI：384(M+H)+
2316	APCI：384(M+H)+
		2317	APCI：384(M+H)+
2318	APCI：385(M+H)+
		2319	APCI：385(M+H)+
2320	APCI：385(M+H)+

Watch 13 (continue)

Compound No.	MASS
		2321	APCI：385(M+H)+
2322	APCI：385(M+H)+
		2323	APCI：387(M+H)+
2324	APCI：387(M+H)+
		2325	APCI：387(M+H)+
2326	APCI：393(M+H)+
		2327	APCI：393(M+H)+
2328	APCI：393(M+H)+
		2329	APCI：397(M+H)+
2330	APCI：397(M+H)+
		2331	APCI：399(M+H)+
2332	APCI：399(M+H)+
		2333	APCI：401(M+H)+
2334	APCI：401(M+H)+
		2335	APCI：401(M+H)+
2336	APCI：401(M+H)+
		2337	APCI：401(M+H)+
2338	APCI：402(M+H)+
		2339	APCI：402(M+H)+
2340	APCI：402(M+H)+
		2341	APCI：402(M+H)+
2342	APCI：402(M+H)+
		2343	APCI：401(M+H)+
2344	APCI：403(M+H)+
		2345	APCI：411(M+H)+
2346	APCI：412(M+H)+
		2347	APCI：412(M+H)+
2348	APCI：417(M+H)+
		2349	APCI：417(M+H)+
2350	APCI：418(M+H)+
		2351	APCI：418(M+H)+
2352	APCI：419(M+H)+
		2353	APCI：419(M+H)+
2354	APCI：419(M+H)+
		2355	APCI：419(M+H)+
2356	APCI：419(M+H)+
		2357	APCI：421(M+H)+
2358	APCI：421(M+H)+
		2359	APCI：423(M+H)+
2360	APCI：425(M+H)+

Compound No.	MASS
		2361	APCI：425(M+H)+
2362	APCI：425(M+H)+
		2363	APCI：425(M+H)+
2364	ESI：429(M+H)+
		2365	APCI：429(M+H)+
2366	APCI：429(M+H)+
		2367	APCI：435(M+H)+
2368	APCI：441(M+H)+
		2369	APCI：452(M+H)+
2370	APCI：453(M+H)+
		2371	APCI：458(M+H)+
2372	APCI：459(M+H)+
		2373	APCI：473(M+H)+
2374	APCI：477(M+H)+
		2375	APCI：257(M+H)+
2376	APCI：261(M+H)+
		2377	APCI：293(M+H)+
2378	APCI：295(M+H)+
		2379	APCI：295(M+H)+
2380	APCI：297(M+H)+
		2381	APCI：307(M+H)+
2382	APCI：309(M+H)+
		2383	APCI：309(M+H)+
2384	APCI：309(M+H)+
		2385	APCI：310(M+H)+
2386	APCI：319(M+H)+
		2387	APCI：319(M+H)+
2388	APCI：320(M+H)+
		2389	APCI：321(M+H)+
2390	APCI：323(M+H)+
		2391	APCI：323(M+H)+
2392	APCI：323(M+H)+
		2393	APCI：323(M+H)+
2394	APCI：325(M+H)+
		2395	APCI：327(M+H)+
2396	APCI：330(M+H)+
		2397	APCI：331(M+H)+
2398	APCI：331(M+H)+
		2399	APCI：331(M+H)+
2400	APCI：332(M+H)+

Watch 13 (continue)

Compound No.	MASS
		2401	APCI：333(M+H)+
2402	APCI：333(M+H)+
		2403	APCI：334(M+H)+
2404	APCI：335(M+H)+
		2405	APCI：335(M+H)+
2406	APCI：336(M+H)+
		2407	APCI：337(M+H)+
2408	APCI：338(M+H)+
		2409	APCI：339(M+H)+
2410	APCI：339(M+H)+
		2411	APCI：344(M+H)+
2412	APCI：344(M+H)+
		2413	APCI：344(M+H)+
2414	APCI：345(M+H)+
		2415	APCI：345(M+H)+
2416	APCI：346(M+H)+
		2417	APCI：346(M+H)+
2418	APCI：346(M+H)+
		2419	APCI：346(M+H)+
2420	APCI：347(M+H)+
		2421	APCI：347(M+H)+
2422	APCI：347(M+H)+
		2423	APCI：347(M+H)+
2424	APCI：347(M+H)+
		2425	APCI：347(M+H)+
2426	APCI：348(M+H)+
		2427	APCI：348(M+H)+
2428	APCI：349(M+H)+
		2429	APCI：350(M+H)+
2430	APCI：351(M+H)+
		2431	APCI：351(M+H)+
2432	APCI：351(M+H)+
		2433	APCI：353(M+H)+
2434	APCI：354(M+H)+
		2435	APCI：355(M+H)+
2436	APCI：355(M+H)+
		2437	APCI：355(M+H)+
2438	APCI：357(M+H)+
		2439	APCI：357(M+H)+
2440	APCI：357(M+H)+

Compound No.	MASS
		2441	APCI：358(M+H)+
2442	APCI：359(M+H)+
		2443	APCI：359(M+H)+
2444	APCI：359(M+H)+
		2445	APCI：360(M+H)+
2446	ESI：360(M+H)+
		2447	APCI：361(M+H)+
2448	APCI：361(M+H)+
		2449	APCI：361(M+H)+
2450	APCI：361(M+H)+
		2451	APCI：361(M+H)+
2452	APCI：364(M+H)+
		2453	APCI：364(M+H)+
2454	APCI：364(M+H)+
		2455	APCI：364(M+H)+
2456	APCI：365(M+H)+
		2457	APCI：367(M+H)+
2458	APCI：368(M+H)+
		2459	APCI：369(M+H)+
2460	APCI：369(M+H)+
		2461	APCI：369(M+H)+
2462	APCI：369(M+H)+
		2463	APCI：369(M+H)+
2464	APCI：369(M+H)+
		2465	APCI：369(M+H)+
2466	APCI：371(M+H)+
		2467	APCI：371(M+H)+
2468	APCI：371(M+H)+
		2469	APCI：371(M+H)+
2470	APCI：372(M+H)+
		2471	APCI：373(M+H)+
2472	APCI：373(M+H)+
		2473	APCI：373(M+H)+
2474	APCI：373(M+H)+
		2475	APCI：373(M+H)+
2476	APCI：373(M+H)+
		2477	APCI：374(M+H)+
2478	APCI：374(M+H)+
		2479	APCI：374(M+H)+
2480	APCI：375(M+H)+

Watch 13 (continue)

Compound No.	MASS
		2481	APCI：375(M+H)+
2482	APCI：376(M+H)+
		2483	APCI：376(M+H)+
2484	APCI：377(M+H)+
		2485	APCI：378(M+H)+
2486	APCI：378(M+H)+
		2487	APCI：379(M+H)+
2488	APCI：379(M+H)+
		2489	APCI：379(M+H)+
2490	APCI：380(M+H)+
		2491	APCI：381(M+H)+
2492	APCI：381(M+H)+
		2493	APCI：381(M+H)+
2494	APCI：381(M+H)+
		2495	APCI：381(M+H)+
2496	APCI：381(M+H)+
		2497	APCI：381(M+H)+
2498	APCI：382(M+H)+
		2499	APCI：382(M+H)+
2500	APCI：382(M+H)+
		2501	APCI：383(M+H)+
2502	APCI：383(M+H)+
		2503	APCI：383(M+H)+
2504	APCI：383(M+H)+
		2505	APCI：384(M+H)+
2506	APCI：385(M+H)+
		2507	APCI：385(M+H)+
2508	APCI：385(M+H)+
		2509	APCI：385(M+H)+
2510	APCI：386(M+H)+
		2511	APCI：387(M+H)+
2512	APCI：387(M+H)+
		2513	APCI：387(M+H)+
2514	APCI：387(M+H)+
		2515	APCI：387(M+H)+
2516	APCI：387(M+H)+
		2517	APCI：387(M+H)+
2518	APCI：388(M+H)+
		2519	APCI：389(M+H)+
2520	APCI：389(M+H)+

Compound No.	MASS
		2521	APCI：389(M+H)+
2522	APCI：389(M+H)+
		2523	APCI：389(M+H)+
2524	APCI：389(M+H)+
		2525	APCI：389(M+H)+
2526	APCI：389(M+H)+
		2527	APCI：390(M+H)+
2528	APCI：390(M+H)+
		2529	APCI：390(M+H)+
2530	APCI：393(M+H)+
		2531	PPCI：393(M+H)+
2532	APCI：395(M+H)+
		2533	APCI：395(M+H)+
2534	APCI：395(M+H)+
		2535	APCI：395(M+H)+
2536	APCI：395(M+H)+
		2537	APCI：395(M+H)+
2538	APCI：396(M+H)+
		2539	APCI：396(M+H)+
2540	APCI：397(M+H)+
		2541	APCI：397(M+H)+
2542	APCI：397(M+H)+
		2543	APCI：397(M+H)+
2544	APCI：397(M+H)+
		2545	APCI：397(M+H)+
2546	APCI：397(M+H)+
		2547	APCI：398(M+H)+
2548	APCI：398(M+H)+
		2549	APCI：398(M+H)+
2550	APCI：398(M+H)+
		2551	APCI：398(M+H)+
2552	APCI：398(M+H)+
		2553	ESI：399(M+H)+
2554	APCI：399(M+H)+
		2555	APCI：399(M+H)+
2556	APCI：399(M+H)+
		2557	APCI：401(M+H)+
2558	APCI：401(M+H)+
		2559	APCI：401(M+H)+
2560	APCI：401(M+H)+

Watch 13 (continue)

Compound No.	MASS
		2561	APCI：401(M+H)+
2562	APCI：403(M+H)+
		2563	APCI：403(M+H)+
2564	APCI：403(M+H)+
		2565	APCI：404(M+H)+
2566	APCI：404(M+H)+
		2567	APCI：404(M+H)+
2568	APCI：404(M+H)+
		2569	APCI：405(M+H)+
2570	APCI：405(M+H)+
		2571	APCI：406(M+H)+
2572	APCI：408(M+H)+
		2573	APCI：408(M+H)+
2574	ESI：409(M+H)+
		2575	APCI：410(M+H)+
2576	APCI：410(M+H)+
		2577	APCI：410(M+H)+
2278	APCI：411(M+H)+
		2579	APCI：412(M+H)+
2580	APCI：412(M+H)+
		2581	APCI：412(M+H)+
2582	APCI：412(M+H)+
		2583	APCI：412(M+H)+
2584	APCI：413(M+H)+
		2585	APCI：413(M+H)+
2586	APCI：413(M+H)+
		2587	APCI：413(M+H)+
2588	APCI：413(M+H)+
		2589	APCI：414(M+H)+
2590	APCI：415(M+H)+
		2591	APCI：415(M+H)+
2592	APCI：415(M+H)+
		2593	APCI：415(M+H)+
2594	APCI：415(M+H)+
		2595	APCI：415(M+H)+
2596	APCI：415(M+H)+
		2597	APCI：416(M+H)+
2598	APCI：417(M+H)+
		2599	APCI：417(M+H)+
2600	APCI：418(M+H)+

Compound No.	MASS
		2601	APCI：418(M+H)+
2602	APCI：419(M+H)+
		2603	APCI：419(M+H)+
2604	APCI：419(M+H)+
		2605	APCI：419(M+H)+
2606	APCI：419(M+H)+
		2607	APCI：421(M+H)+
2608	APCI：421(M+H)+
		2609	APCI：421(M+H)+
2610	APCI：421(M+H)+
		2611	APCI：422(M+H)+
2612	APCI：422(M+H)+
		2613	APCI：423(M+H)+
2614	APCI：425(M+H)+
		2615	APCI：427(M+H)+
2616	APCI：427(M+H)+
		2617	APCI：427(M+H)+
2618	APCI：427(M+H)+
		2619	APCI：427(M+H)+
2620	APCI：427(M+H)+
		2621	APCI：428(M+H)+
2622	APCI：428(M+H)+
		2623	APCI：428(M+H)+
2624	APCI：429(M+H)+
		2625	APCI：429(M+H)+
2626	APCI：429(M+H)+
		2627	APCI：431(M+H)+
2628	APCI：431(M+H)+
		2629	APCI：431(M+H)+
2630	APCI：432(M+H)+
		2631	APCI：432(M+H)+
2632	APCI：435(M+H)+
		2633	APCI：437(M+H)+
2634	APCI：437(M+H)+
		2635	APCI：438(M+H)+
2636	APCI：439(M+H)+
		2637	APCI：439(M+H)+
2638	APCI：439(M+H)+
		2639	APCI：440(M+H)+
2640	APCI：441(M+H)+

Watch 13 (continue)

Compound No.	MASS
		2641	APCI：443(M+H)+
2642	APCI：444(M+H)+
		2643	APCI：444(M+H)+
2644	APCI：448(M+H)+
		2645	APCI：449(M+H)+
2646	APCI：449(M+H)+
		2647	APCI：449(M+H)+
2648	APCI：453(M+H)+
		2649	APCI：454(M+H)+
2650	APCI：455(M+H)+
		2651	APCI：455(M+H)+
2652	APCI：456(M+H)+
		2653	APCI：457(M+H)+
2654	APCI：459(M+H)+
		2655	APCI：462(M+H)+
2656	APCI：462(M+H)+
		2657	APCI：462(M+H)+
2658	APCI：463(M+H)+
		2659	APCI：465(M+H)+
2660	APCI：465(M+H)+
		2661	APCI：465(M+H)+
2662	APCI：471(M+H)+
		2663	APCI：475(M+H)+
2664	APCI：476(M+H)+
		2665	APCI：477(M+H)+
2666	APCI：478(M+H)+
		2667	APCI：482(M+H)+
2668	APCI：483(M+H)+
		2669	APCI：492(M+H)+
2670	APCI：494(M+H)+
		2671	APCI：495(M+H)+
2672	APCI：497(M+H)+
		2673	APCI：497(M+H)+
2674	APCI：498(M+H)+
		2675	APCI：508(M+H)+
2676	APCI：523(M+H)+
		2677	APCI：531(M+H)+
2678	APCI：533(M+H)+

TABLE 14

No.	MASS
		3001	ESI(Pos)250(M+H)
3002	ESI(Pos)264(M+H)
		3003	ESI(Pos)278(M+H)
3004	ESI(Pos)278(M+H)
		3005	ESI(Pos)292(M+H)
3006	ESI(Pos)292(M+H)
		3007	ESI(Pos)292(M+H)
3008	ESI(Pos)306(M+H)
		3009	ESI(Pos)306(M+H)
3010	ESI(Pos)306(M+H)
		3011	ESI(Pos)290(M+H)
3012	ESI(Pos)318(M+H)
		3013	ESI(Pos)332(M+H)
3014	ESI(Pos)326(M+H)
		3015	ESI(Pos)340(M+H)
3016	ESI(Pos)354(M+H)
		3017	ESI(Pos)402(M+H)
3018	ESI(Neg)330(M+H)
		3019	ESI(Pos)342(M+H)
3020	ESI(Pos)356(M+H)
		3021	ESI(Pos)280(M+H)
3022	ESI(Pos)340(M+H)
		3023	ESI(Pos)356(M+H)
3024	ESI(Pos)356(M+H)
		3025	ESI(Pos)310(M+H)
3026	ESI(Pos)308(M+H)
		3027	ESI(Pos)384(M+H)
3028	ESI(Pos)404(M+H)
		3029	ESI(Pos)338(M+H)
3030	ESI(Pos)280(M+H)
		3031	ESI(Pos)310(M+H)
3032	ESI(Pos)321(M+H)
		3033	ESI(Pos)322(M+H)
3034	ESI(Pos)276(M+H)
		3035	ESI(Pos)290(M+H)
3036	ESI(Pos)304(M+H)
		3037	ESI(Pos)318(M+H)
3038	ESI(Pos)370(M+H)
		3039	ESI(Pos)352(M+H)
3040	ESI(Pos)414(M+H)

No.	MASS
		3041	ESI(Pos)312(M+H)
3042	ESI(Pos)326(M+H)
		3043	ESI(Pos)326(M+H)
3044	ESI(Pos)326(M+H)
		3045	ESI(Pos)330(M+H)
3046	ESI(Pos)330(M+H)
		3047	ESI(Pos)330(M+H)
3048	ESI(Pos)337(M+H)
		3049	ESI(Pos)337(M+H)
3050	ESI(Pos)340(M+H)
		3051	ESI(Pos)340(M+H)
3052	ESI(Pos)340(M+H)
		3053	ESI(Pos)342(M+H)
3054	ESI(Pos)342(M+H)
		3055	ESI(Pos)344(M+H)
3056	ESI(Pos)344(M+H)
		3057	ESI(Pos)346(M+H)
3058	ESI(Pos)346(M+H)
		3059	ESI(Pos)346(M+H)
3060	ESI(Pos)348(M+H)
		3061	ESI(Pos)348(M+H)
3062	ESI(Pos)348(M+H)
		3063	ESI(Pos)348(M+H)
3064	ESI(Pos)348(M+H)
		3065	ESI(Pos)348(M+H)
3066	ESI(Pos)354(M+H)
		3067	ESI(Pos)354(M+H)
3068	ESI(Pos)356(M+H)
		3069	ESI(Pos)357(M+H)
3070	ESI(Pos)362(M+H)
		3071	ESI(Pos)362(M+H)
3072	ESI(Pos)362(M+H)
		3073	ESI(Pos)362(M+H)
3074	ESI(Pos)364(M+H)
		3075	ESI(Pos)364(M+H)
3076	ESI(Pos)364(M+H)
		3077	ESI(Pos)364(M+H)
3078	ESI(Pos)364(M+H)
		3079	ESI(Pos)366(M+H)
3080	ESI(Pos)366(M+H)

Watch 14 (continue)

No.	MASS
		3081	ESI(Pos)366(M+H)
3082	ESI(Pos)366(M+H)
		3083	ESI(Pos)368(M+H)
3084	ESI(Pos)392(M+H)
		3085	ESI(Pos)372(M+H)
3086	ESI(Pos)378(M+H)
		3087	ESI(Pos)378(M+H)
3088	ESI(Pos)380(M+H)
		3089	ESI(Pos)380(M+H)
3090	ESI(Neg)378(M+H)
		3091	ESI(Pos)380(M+H)
3092	ESI(Pos)380(M+H)
		3093	ESI(Pos)382(M+H)
3094	ESI(Pos)382(M+H)
		3095	ESI(Pos)382(M+H)
3096	ESI(Pos)384(M+H)
		3097	ESI(Pos)388(M+H)
3098	ESI(Pos)390(M+H)
		3099	ESI(Pos)390(M+H)
3100	ESI(Pos)390(M+H)
		3101	ESI(Pos)396(M+H)
3102	ESI(Pos)396(M+H)
		3103	ESI(Pos)396(M+H)
3104	ESI(Pos)398(M+H)
		3105	ESI(Pos)398(M+H)
3106	ESI(Pos)398(M+H)
		3107	ESI(Pos)398(M+H)
3108	ESI(Pos)398(M+H)
		3109	ESI(Pos)398(M+H)
3110	ESI(Pos)398(M+H)
		3111	ESI(Pos)400(M+H)
3112	ESI(Pos)402(M+H)
		3113	ESI(Pos)402(M+H)
3114	ESI(Pos)404(M+H)
		3115	ESI(Pos)412(M+H)
3116	ESI(Pos)414(M+H)
		3117	ESI(Pos)414(M+H)
3118	ESI(Pos)418(M+H)
		3119	ESI(Pos)432(M+H)
3120	ESI(Pos)438(M+H)

No.	MASS
		3121	ESI(Pos)438(M+H)
3122	ESI(Pos)438(M+H)
		3123	ESI(Pos)442(M+H)
3124	ESI(Pos)448(M+H)
		3125	ESI(Pos)448(M+H)
3126	ESI(Pos)355(M+H)
		3127	ESI(Pos)396(M+H)
3128	ESI(Pos)313(M+H)
		3129	ESI(Pos)313(M+H)
3130	ESI(Pos)364(M+H)
		3131	ESI(Pos)377(M+H)
3132	ESI(Pos)395(M+H)
		3133	ESI(Pos)421(M+H)
3134	ESI(Pos)439(M+H)
		3135	ESI(Pos)302(M+H)
3136	ESI(Pos)303(M+H)
		3137	ESI(Pos)317(M+H)
3138	ESI(Pos)318(M+H)
		3139	ESI(Pos)347(M+H)
3140	ESI(Pos)330(M+H)
		3141	ESI(Pos)331(M+H)
3142	ESI(Pos)344(M+H)
		3143	ESI(Pos)372(M+H)
3144	ESI(Pos)372(M+H)
		3145	ESI(Pos)364(M+H)
3146	ESI(Pos)368(M+H)
		3147	ESI(Pos)368(M+H)
3148	ESI(Pos)368(M+H)
		3149	ESI(Pos)396(M+H)
3150	ESI(Pos)400(M+H)
		3151	ESI(Pos)403(M+H)
3152	ESI(Pos)420(M+H)
		3153	ESI(Pos)427(M+H)
3154	ESI(Pos)446(M+H)
		3155	ESI(Pos)448(M+H)
3156	ESI(Pos)454(M+H)
		3157	ESI(Pos)462(M+H)
3158	ESI(Pos)480(M+H)

Watch 15

No.	MASS
		3159	APCI：317(M+H)+
3160	APCI：317(M+H)+
		3161	APCI：317(M+H)+
3162	APCI：318(M+H)+
		3163	APCI：318(M+H)+
3164	APCI：318(M+H)+
		3165	APCI：318(M+H)+
3166	APCI：331(M+H)+
		3167	APCI：331(M+H)+
3468	APCI：331(M+H)+
		3169	APCI：331(M+H)+
3170	APCI：331(M+H)+
		3171	APCI：331(M+H)+
3172	APCI：331(M+H)+
		3173	APCI：332(M+H)+
3174	APCI：333(M+H)+
		3175	APCI：333(M+H)+
3176	APCI：333(M+H)+
		3177	APCI：333(M+H)+
3178	APCI：335(M+H)+
		3179	APCI：335(M+H)+
3180	APCI：335(M+H)+
		3181	APCI：335(M+H)+
3182	APCI：342(M+H)+
		3183	APCI：345(M+H)+
3184	APCI：345(M+H)+
		3185	APCI：345(M+H)+
3186	APCI：345(M+H)+
		3187	APCI：347(M+H)+
3188	APCI：347(M+H)+
		3189	APCI：348(M+H)+
3190	APCI：349(M+H)+
		3191	APCI：351(M+H)+
3192	APCI：351(M+H)+
		3193	APCI：351(M+H)+
3194	APCI：351(M+H)+
		3195	APCI：351(M+H)+
3196	APCI：352(M+H)+
		3197	APCI：353(M+H)+
3198	APCI：360(M+H)+

No.	MASS
		3199	APCI：361(M+H)+
3200	APCI：361(M+H)+
		3201	APCI：363(M+H)+
3202	APCI：365(M+H)+
		3203	APCI：365(M+H)+
3204	APCI：369(M+H)+
		3205	APCI：371(M+H)+
3206	APCI：374(M+H)+
		3207	APCI：377(M+H)+
3208	APCI：378(M+H)+
		3209	APCI：378(M+H)+
3210	APCI：381(M+H)+
		3211	APCI：383(M+H)+
3212	APCI：383(M+H)+
		3213	APCI：384(M+H)+
3214	APCI：385(M+H)+
		3215	APCI：385(M+H)+
3216	APCI：385(M+H)+
		3217	APCI：385(M+H)+
3218	APCI：385(M+H)+
		3219	APCI：385(M+H)+
3220	APCI：385(M+H)+
		3221	APCI：385(M+H)+
3222	APCI：385(M+H)+
		3223	APCI：385(M+H)+
3224	APCI：386(M+H)+
		3225	APCI：386(M+H)+
3226	APCI：386(M+H)+
		3227	APCI：386(M+H)+
3228	APCI：389(M+H)+
		3229	APCI：391(M+H)+
3230	APCI：393(M+H)+
		3231	APCI：395(M+H)+
3232	APCI：395(M+H)+
		3233	APCI：395(M+H)+
3234	APCI：395(M+H)+
		3235	APCI：395(M+H)+
3236	APCI：399(M+H)+
		3237	APCI：399(M+H)+
3238	APCI：399(M+H)+

Watch 15 (continuation)

No.	MASS
		3239	APCI：400(M+H)+
3240	APCI：403(M+H)+
		3241	APCI：405(M+H)+
3242	APCI：409(M+H)+
		3243	APCI：410(M+H)+
3244	APCI：415(M+H)+
		3245	APCI：414(M+H)+
3246	APCI：415(M+H)+
		3247	APCI：418(M+H)+
3248	APCI：418(M+H)+
		3249	APCI：419(M+H)+
3250	ESI：423(M+H)+
		3251	APCI：425(M+H)+
3252	APCI：427(M+H)+
		3253	APCI：440(M+H)+
3254	APCI：443(M+H)+
		3255	APCI：355(M+H)+
3255	APCI：355(M+H)+
		3257	APCI：355(M+H)+
3258	APCI：355(M+H)+
		3259	APCI：356(M+H)+
3260	APCI：356(M+H)+
		3261	APCI：367(M+H)+
3262	APCI：367(M+H)+
		3263	APCI：367(M+H)+
3264	APCI：367(M+H)+
		3265	APCI：367(M+H)+
3266	APCI：368(M+H)+
		3267	APCI：368(M+H)+
3268	APCI：368(M+H)+
		3269	APCI：368(M+H)+
3270	APCI：368(M+H)+
		3271	APCI：369(M+H)+
3272	APCI：370(M+H)+
		3273	APCI：371(M+H)+
3274	APCI：372(M+H)+
		3275	APCI：373(M+H)+
3276	APCI：374(M+H)+
		3277	APCI：381(M+H)+
3278	APCI：381(M+H)+

No.	MASS
		3279	APCI：382(M+H)+
3280	APCI：382(M+H)+
		3281	APCI：383(M+H)+
3282	APCI：283(M+H)+
		3283	APCI：387(M+H)+
3284	APCI：387(M+H)+
		3285	APCI：399(M+H)+
3286	APCI：401(M+H)+
		3287	APCI：409(M+H)+
3288	APCI：414(M+H)+
		3289	APCI：419(M+H)+
3290	APCI：419(M+H)+
		3291	APCI：421(M+H)+
3292	APCI：435(M+H)+
		3293	APCI：441(M+H)+
3294	APCI：443(M+H)+
		3295	APCI：444(M+H)+
3296	APCI：456(M+H)+
		3297	APCI：477(M+H)+
3298	APCI：359(M+H)+
		3299	APCI：359(M+H)+
3300	APCI：381(M+H)+
		3301	APCI：381(M+H)+
3302	APCI：381(M+H)+
		3303	APCI：382(M+H)+
3304	APCI：382(M+H)+
		3305	APCI：385(M+H)+
3306	APCI：387(M+H)+
		3307	APCI：398(M+H)+
3308	APCI：398(M+H)+
		3309	APCI：399(M+H)+
3310	APCI：400(M+H)+
		3311	APCI：401(M+H)+
3312	APCI：402(M+H)+
		3313	APCI：410(M+H)+
3314	APCI：413(M+H)+
		3315	APCI：414(M+H)+
3316	APCI：415(M+H)+
		3317	APCI：419(M+H)+
3318	APCI：427(M+H)+

Watch 15 (continuation)

No.	MASS
		3319	APCI：431(M+H)+
3320	APCI：435(M+H)+
		3321	APCI：444(M+H)+
3322	APCI：449(M+H)+
		3323	APCI：449(M+H)+
3324	APCI：451(M+H)+
		3325	APCI：451(M+H)+
3326	APCI：459(M+H)+
		3327	APCI：483(M+H)+

Test example 1 human CB2 receptor binding inhibition test

A cDNA sequence encoding the human CB2 receptor (Munro et al, Nature, 1993, 365, 61-65) was inserted upstream of the CMV promoter of an expression vector pTARGET for animal cells (Promega Co.). The obtained expression vector was transfected into a host cell CHO-DHFR (-) by Lipofectamine (Invitrogen) to obtain a CB2 receptor-stably expressing cell.

A membrane fraction prepared from a CHO cell stably expressing a CB2 receptor, a test compound and³H]CP-55,940 (final concentration 0.57 nM: Perkin Elmer Co.) was added together in Assay buffer (50mM Tris-HCl buffer (pH7.4), 2.5mM EDTA, 5mM MgCl) containing 0.2% bovine serum albumin₂) After 2 hours of incubation at 25 ℃ the cells were filtered through GF/C filters (glass filters) treated with 0.1% poly-L-lysine (SIGMA). After washing with Assay buffer containing 0.1% bovine serum albumin, radioactivity on the glass filter was determined by a liquid scintillation counter. Nonspecific binding was measured in the presence of 2.0. mu.MCP-55,940 (Tocris Co.) to determine the 50% Inhibitory Concentration (IC) of the test compound for specific binding₅₀Value). The test results are shown in Table 16. As shown in the table, the tested compounds showed affinity for the CB2 receptor.

TABLE 16 human CB2 receptor binding inhibition assay

Compound No.	CB2IC50(nM)
		9	11.3
12	13.3
		23	8.9
24	7.5
		25	17.4
29	8.6
		30	6.6
33	8.2
		34	6.6
35	3.4
		36	2.2
37	11.3
		41	1.4
45	16.5
		46	1.2
51	2.6
		54	18.7
56	0.8
		57	3.8
58	1.8
		59	7.2
63	4.9

Compound No.	CB2IC50(nM)
		67	3.0
70	14.9
		71	5.9
73	10.2
		74	4.6
76	14.4
		77	19.3
78	9.8
		79	8.4
80	17.9
		81	12.3
85	18.9
		86	6.5
88	17.8
		89	9.8
90	6.5
		91	7.9
92	3.9
		93	17.6
94	2.9
		96	7.7
97	3.3

Compound No.	CB2IC50(nM)
		99	6.5
100	7.0
		104	1.7
105	1.7
		106	6.5
107	0.5
		109	1.3
113	1.1
		114	1.6
115	0.5
		117	5.8
119	18.5
		120	7.4
122	8.9
		129	7.1
130	8.5
		131	5.6
132	15.7
		133	7.3
134	6.6
		135	11.9
136	11.6

Compound No.	CB2IC50(nM)
		138	12.0
139	7.4
		140	6.1
141	13.9
		143	7.4
144	4.3
		145	3.9
146	6.6
		147	9.6
149	12.2
		150	15.0
151	3.2
		153	17.8
154	5.9
		155	4.3
156	11.4
		157	12.1
158	7.1
		159	8.4
160	8.5
		161	9.7
162	12.0

Watch 16 (continuation)

Compound No.	CB2IC50(nM)
		163	14.9
164	4.1
		165	4.3
166	7.2
		167	4.6
168	5.4
		170	13.8
174	11.7
		179	17.8
180	1.0
		181	0.8
182	0.3
		183	0.5
184	12.0
		185	11.0
186	1.7
		187	17.0
189	1.5
		190	1.0
191	0.7
		192	13.2
194	19.1

Compound No.	CB2IC50(nM)
		195	3.2
196	7.6
		197	2.0
198	2.7
		200	15.1
201	19.1
		206	5.7
209	1.4
		210	15.7
211	12.0
		215	1.1
216	1.7
		217	2.6
218	5.7
		219	2.1
220	3.9
		221	15.6
222	11.3
		223	2.0
224	13.0
		225	3.9
226	7.7

Compound No.	CB2IC50(nM)
		227	8.2
228	0.5
		229	1.0
230	1.5
		231	3.0
232	0.5
		234	0.7
235	3.4
		236	2.0
237	13.1
		238	4.4
239	2.4
		240	3.4
241	1.0
		242	4.0
243	0.4
		244	3.2
245	0.8
		246	0.8
247	0.3
		248	5.6
249	0.4

Compound No.	CB2IC50(nM)
		250	1.1
251	3.4
		254	1.4
255	0.6
		256	1.1
257	1.3
		258	0.6
261	1.0
		262	0.6
263	0.6
		264	1.0
265	1.0
		266	0.8
267	1.1
		268	1.1
269	3.6
		270	0.7
272	5.0
		274	13.2
277	9.0
		282	14.5
283	5.9

Watch 16 (continuation)

Compound No.	CB2IC50(nM)
		284	1.2
285	14.2
		286	12.7
287	13.5
		288	0.2
289	0.5
		293	7.0
295	12.3
		298	1.5
299	2.8
		300	15.0
301	2.0
		304	2.3
305	3.7
		306	0.5
307	1.0
		308	3.6
309	2.1
		310	17.3
312	14.0
		316	5.3
319	18.6

Compound No.	CB2IC50(nM)
		320	6.2
321	2.3
		322	5.6
323	6.2
		324	2.0
325	13.0
		326	2.9
327	3.6
		328	11.8
330	13.8
		332	3.3
335	5.5
		336	2.9
337	2.8
		338	9.1
341	5.3
		344	12.2
345	12.7
		346	13.5
348	3.8
		349	1.9
350	5.2

Compound No.	CB2IC50(nM)
		351	2.2
352	2.3
		365	3.4
369	1.4
		382	17.0
387	13.7
		399	6.8
402	15.4
		410	7.1
411	8.7
		427	5.9
470	10.6
		470	10.6
474	4.9
		478	3.9
481	3.4
		482	1.2
483	8.3
		484	2.7
485	1.1
		486	5.1
487	9.9

Compound No.	CB2IC50(nM)
		488	4.0
489	6.0
		490	10.0
491	9.3
		492	5.0
493	1.9
		494	2.1
495	6.3
		504	15.4
509	5.9
		510	13.2
513	16.9
		514	2.6

Test example 2 human CB1 receptor binding inhibition test

Binding test to human CB1 receptor CHO-DHFR (-) cells stably expressing CB1 receptor were prepared in the same manner as in test example 1, and the 50% Inhibitory Concentration (IC) of the test compound was determined₅₀Value). The test results are shown in Table 17. As shown in the table, the tested compounds showed affinity for the CB1 receptor.

TABLE 17 human CB1 receptor binding inhibition assay

Compound No.	CB1IC50(nM)
		56	294
104	327
		107	18
115	25
		180	395
181	115
		182	22
183	138
		186	271
189	212
		190	53
191	193
		206	460
215	61
		223	168
228	228
		229	263
232	211
		235	315

Compound No.	CB1IC50(nM)
		236	215
237	200
		240	168
243	73
		245	32
246	319
		247	3
249	2
		256	102
258	19
		261	375
262	435
		263	56
264	181
		265	100
286	435
		288	49
289	136
		295	497

Compound No.	CB1IC50(nM)
		299	28
301	191
		304	372
306	68
		308	336
309	405
		323	362
324	353
		327	55
332	98
		486	211
487	248
		490	291
491	172
		492	265
494	279

Test example 3 human CB1 receptor mediated GTP γ S binding assay

CHO cells stably expressing human CB1 receptor were prepared in the same manner as in test example 2, and the membrane fraction was mixed with the test compound in Assay buffer [50mM Tris-HCl (pH7.4), 2.5mM EDTA, 5mM MgCl ] containing 0.2% bovine serum albumin₂3 μ MGDP (SIGMA Corp.), 30 μ g/ml Saponin (SIGMA Corp.)]In (b), after incubation at 30 ℃ for 30 minutes, 0.1nM [2 ]³⁵S]GTP γ S (Perkin Elmer) was incubated at 30 ℃ for 30 minutes. After washing by GF/C filtration, the radioactivity on the glass filter was determined by liquid scintillation counting. Nonspecific binding was measured in the absence of the compound, and the Effective Concentration (EC) of 50% was determined by setting the maximum activity value of each test compound as 100%₅₀Value).

EC of Compounds No.247 and No.249 tested₅₀Values were 33nM and 19nM, respectively, and the compounds of the present invention showed agonistic effects on the CB1 receptor.

Test example 4 human CB2 receptor mediated GTP γ S binding assay

CHO cells stably expressing human CB2 receptor were prepared in the same manner as in test example 1, and the GTPrS binding test was carried out in the same manner as in test example 3 to determine the 50% Effective Concentration (EC) of the maximum activity of the test compound₅₀Value).

EC for Compounds No.9, No.184, No.267 and No.474 to be tested₅₀Values of 23.7nM, 9.8nM, 0.4nM and 2.3nM, respectively, the compounds of the present invention showed agonistic effects on the CB2 receptor.

Test example 5 mouse acetic acid writhing test

This assay was performed according to Futaki N et al (Gen Pharmacol.24 (1): 105-110 (1993)). The test compound suspended in a 5% gum arabic solution was orally administered using Jcl: ICR line male mice (5 weeks old). 1 hour after the test compound was administered, a 0.9% aqueous acetic acid solution was intraperitoneally administered, and the number of abdominal extension exercises (painful behaviors) was measured within 10 minutes after 5 minutes. The control group was orally administered with a 5% gum arabic solution alone, and the pain behavior inhibition (%) was calculated using the following formula.

[ number 1]

The 30mg/kg inhibition rates of the tested compounds No.59, No.247, No.267, No.411, No.474 and No.510 by oral administration were 44.8%, 93.0%, 59.9%, 49.0%, 61.9% and 19.6%, respectively, and the compounds of the present invention showed analgesic effects.

Test example 6 neuropathic pain test in rat

Using an SD: IGS male rats (5 weeks old) were subjected to a neuropathic pain model prepared by ligating the sciatic nerve portion of the thigh by the method of Seltzer et al (Seltzer Z; pain.43 (2): 205;. 218(1990)), and the change in pain threshold (the number of grams of fibers loaded in response to the contact stimulus) was measured by stimulating the injured sole of the affected part with von Frey filenamet (nylon fibers for touch stimulus examination; North Coast Medical, Inc.). The test compound was suspended in a 5% gum arabic solution and administered orally in amounts of 0mg/kg, 3mg/kg, 10mg/kg and 30mg/kg, and the pain threshold (g) was determined after 1 hour.

Oral administration of test compound No.184 increased the pain threshold with dose, improving pain hypersensitivity (fig. 1).

Test example 7 mouse ear edema test

The test compound was dissolved in acetone and applied to 20. mu.L of the inner side of the auricle using Balb/c male mice (5 weeks old). After 10 minutes of application of the test compound, a solution containing 0.8. mu.g of PMA (phorbol 12-myrisitate 13-acetate) in acetone (20. mu.L) was applied, and after 5 hours, the auricular thickening was measured using a dial linking gauge. The control group was treated with acetone alone, and the suppression rate (%) of edema in auricle was calculated by the following formula.

Number 2

The test compounds No.184, No.267 and No.474, administered at 1mg in one band of mouse auricle, showed 65%, 84% and 37% inhibition, respectively, and the compounds of the present invention showed anti-edema effect.

Industrial applicability

The present invention provides imine compounds having cannabinoid receptor agonistic action. The imine compound of the present invention has a cannabinoid receptor agonistic action and is useful as a therapeutic or prophylactic agent for pain and autoimmune diseases.

Drawings

FIG. 1 shows the results of the neuropathic pain test in rat of test example 6.

Claims (56)

1. A cannabinoid receptor agonist comprising an imine compound represented by the formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient.

[ wherein A represents any ring represented by the following formulae (wherein X represents an oxygen atom or a sulfur atom, and X' represents a CH or a nitrogen atom),

R¹to represent

A hydrogen atom;

a halogen atom;

c which may be substituted by "aryl substituted by halogen atom_1-10An alkyl group;

C_3-10a cycloalkyl group;

C_2-6an alkenyl group;

C_1-6a haloalkyl group;

C_1-10an alkoxy group;

a carboxyl group;

C_2-6an alkoxycarbonyl group;

hydroxy radical C_1-6An alkyl group;

formula-N (R)⁶)R⁷(in the formula, R⁶And R⁷Each represents a hydrogen atom or C_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom);

formula-CON (R)⁶¹)R⁷¹(in the formula, R⁶¹And R⁷¹Each represents a hydrogen atom or C which may be substituted by a cyclic amino group_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom); or

Can be selected from C_1-6Alkyl radical, C_1-6Aryl substituted with 1 to 3 groups of a halogenated alkyl group and a halogen atom,

R²and R³Respectively represent

A hydrogen atom;

a halogen atom;

C_1-6an alkyl group;

C_1-6a haloalkyl group; or

Can be selected from C_1-6Alkyl radical, C_1-6Aryl substituted with 1 to 3 groups of a halogenated alkyl group and a halogen atom,

R⁴to represent

C_1-10An alkyl group;

C_1-6a haloalkyl group;

quilt C_3-10Cycloalkyl radical, C_1-6Alkoxy, hydroxy, amino, phthalimido, cyano, arylthio, C_2-6Alkoxycarbonyl, carboxyl, formula-CON (R)⁶²)R⁷²(in the formula, R⁶²And R⁷²Each represents a hydrogen atom or C_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom), or may be represented by "C_1-6Haloalkyl, C_2-6Alkoxycarbonyl, carboxy or N-piperidinocarbonyl "substituted aryl substituted C_1-10Alkyl or C_2-6An alkenyl group;

C_2-6a haloalkenyl group;

C_2-6an alkynyl group;

1, 1-dioxotetrahydrothienyl;

or an aryl group, or a salt thereof,

R⁵to represent

A hydrogen atom;

C_1-10an alkoxy group;

C_1-6alkoxy radical C_1-6An alkoxy group;

C_1-6a haloalkyl group;

may be selected from halogen atoms, C_3-10Cycloalkyl radical, C_2-6Alkoxycarbonyl group, C_1-6Haloalkyl, optionally substituted by "C_1-6Alkoxy or aryl "substituted C_1-6Alkoxy, optionally substituted by 1 to 2C_1-6Alkyl substituted C_3-10Cycloalkoxy, which may be selected from "C_1-6Alkyl radical, C_1-6Alkoxy radical, C_1-6Haloalkyl, C_1-6Aryl or aryloxy substituted with 1 to 5 groups of haloalkoxy, aralkyloxy, nitro and halogen atoms', heterocyclic group, phthalimido group, C_1-6Alkanoyloxy, aralkyloxy, C_1-6Alkylthio, arylthio and-N (R)⁶²)R⁷²(in the formula, R⁶²And R⁷²Each represents a hydrogen atom or C_1-6Alkyl or a group which forms a cyclic amino group together with an adjacent nitrogen atom) and C substituted with 1 to 3 groups_1-10Alkyl or C_2-6An alkenyl group;

can be covered with C_1-6Alkyl radical, C_1-6Alkoxy radical, C_2-6Alkoxycarbonyl group, C_1-6Haloalkyl or C_1-6Haloalkoxy-substituted aryloxy;

an aralkyloxy group;

a group represented by the formula (II),

{ wherein, B represents

C_3-10A cycloalkyl group;

an aryl group;

a heterocyclic group;

C_2-6a cyclic amino group;

a fluorenyl group;

a phthalimido group;

2-oxopyrrolidinyl;

a group represented by the formula (III);

(wherein n represents 0 or 1.)

Or a group represented by formula (IV);

(wherein Y represents- (CH)₂)p-、-CO-CH₂-CH₂-、-CO-CH₂-CH₂-CH₂-、-O-CH₂-CH₂-、-O-CH₂-CH ═ CH-or-O- (CH)₂) q-O-, p represents an integer of 2 to 4, q represents an integer of 1 to 3)

R⁵⁵To represent

A hydrogen atom;

a halogen atom;

can be: an aryl group, a heterocyclic group or an aryloxy group which may be substituted with a halogen atom; or formula-N (R)⁶²)R⁷²(in the formula, R⁶²And R⁷²Each represents a hydrogen atom or C_1-6Alkyl, orThose represent a group which is bonded to an adjacent nitrogen atom to form a cyclic amino group) or a salt thereof_1-10An alkyl group;

C_1-6a haloalkyl group;

C_1-10an alkoxy group;

C_1-6an alkylthio group;

C_1-6an alkylsulfonyl group;

can be covered with C_1-6Arylsulfonyl substituted with an alkyl group or a halogen atom;

C_1-6a haloalkoxy group;

C_1-6a haloalkylthio group;

C_3-10a cycloalkyl group;

C_2-6an alkenyl group;

C_2-6an alkenyloxy group;

C_2-6an alkenylthio group;

C_1-6alkoxy radical C_1-6An alkoxy group;

can be selected from C_1-6Alkyl radical, C_1-6Haloalkyl group, halogen atom, C_1-6Aryl substituted with 1 to 3 groups of alkoxy, cyano and nitro;

can be covered with C_1-6Alkyl or C_1-6A haloalkyl substituted heterocyclic group;

may be substituted by halogen atoms or C_1-6An alkyl-substituted aryloxy or arylthio group;

formula-N (R)⁶³)R⁷³(in the formula, R⁶³And R⁷³Each represents a hydrogen atom, C_1-6Alkyl radical, C_1-6Hydroxyalkyl radical, C_1-6Alkoxy radical C_1-6Alkyl, aryl, C_1-6Alkanoyl, di-C_1-6Alkylamino radical C_2-6Alkanoyl, benzoyl or can be substituted by C_1-6An alkyl-substituted heterocyclic group, or a group which represents a cyclic amino group bonded together with an adjacent nitrogen atom);

a hydroxyl group;

a cyano group;

a nitro group;

C_1-6an alkanoyl group;

C_1-6an alkanoyloxy group;

C_1-6alkanoyloxy group C_1-6An alkyl group;

C_2-6a haloalkanoyl group;

a carboxyl group;

C_2-6an alkoxycarbonyl group;

c which may be substituted by aryl_2-6A cyclic amino group;

formula-CON (R)⁶⁴)R⁷⁴(in the formula, R⁶⁴And R⁷⁴Each represents a hydrogen atom, C_1-6Alkyl radical, C_1-6Alkoxy radical C_1-6Alkyl, or may be substituted by C_1-6An alkyl-substituted heterocyclic group, or a group which represents a cyclic amino group bonded together with an adjacent nitrogen atom);

formula-SO₂N(R⁶²)R⁷²(in the formula, R⁶²And R⁷²Each represents a hydrogen atom or C_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom);

C_1-6an alkylsulfinyl group;

c which may be substituted by halogen atoms_1-6An alkylsulfonyl group; or

Arylsulfonyl which may be substituted by a halogen atom,

R⁵⁶to represent

A hydrogen atom;

a halogen atom;

can be: can be represented by "C_1-6Alkyl or halogen atoms "substituted aryl, pyridyl, thienyl or heterocyclic groups_1-10An alkyl group;

C_1-6a haloalkyl group;

C_3-10a cycloalkyl group;

C_1-10an alkoxy group;

C_2-6an alkenyl group;

can be selected from C_1-6Alkyl group, halogen atom, C_1-6Aryl substituted with 1 to 3 groups of alkoxy and nitro;

can be covered with C_1-6An alkyl-substituted heterocyclic group;

C_1-6an alkanoyl group;

C_1-6an alkylsulfinyl group;

C_1-6an alkylsulfonyl group;

arylsulfonyl which may be substituted by a halogen atom;

a hydroxyl group;

a cyano group; or

The nitro group(s),

R⁵⁷to represent

A hydrogen atom;

c which may be substituted by "pyridyl or thienyl_1-10An alkyl group;

C_1-6a haloalkyl group;

C_3-10a cycloalkyl group;

a halogen atom;

C_2-6an alkenyl group;

an aryl group which may be substituted with a halogen atom;

C_1-10an alkoxy group;

C_1-6an alkanoyl group; or

C_1-6An alkylsulfinyl group which is a substituent of a fatty acid,

m represents an integer of 1 to 3 }

a and b each represent 0 or 1,

w represents-CO-, -CO-NH-, -CS-NH-or-SO₂-。]

2. The cannabinoid receptor agonist according to claim 1,

with R¹Is a hydrogen atom;

a halogen atom;

c which may be substituted by "aryl substituted by halogen atom_1-10An alkyl group;

C_3-10a cycloalkyl group;

C_1-6a haloalkyl group;

C_1-10an alkoxy group;

a carboxyl group;

C_2-6an alkoxycarbonyl group;

hydroxy radical C_1-6An alkyl group;

formula-N (R)⁶)R⁷(in the formula, R⁶And R⁷Each represents a hydrogen atom or C_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom);

formula-CON (R)⁶¹)R⁷¹(in the formula, R⁶¹And R⁷¹Each represents a hydrogen atom or C which may be substituted by a cyclic amino group_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom); or

Can be selected from C_1-6Alkyl radical, C_1-6Aryl substituted with 1 to 3 groups of a halogenated alkyl group and a halogen atom,

R⁴is composed of

C_1-10An alkyl group;

C_1-6a haloalkyl group;

quilt C_3-10Cycloalkyl radical, C_1-6Alkoxy, hydroxy, amino, phthalimido, cyano, arylthio, C_2-6Alkoxycarbonyl, carboxyl, formula-CON (R)⁶²)R⁷²(in the formula, R⁶²And R⁷²Each represents a hydrogen atom or C_1-6Alkyl, or a group which forms a cyclic amino group together with the adjacent nitrogen atom) or may be represented by "C_1-6Haloalkyl, C_2-6Alkoxycarbonyl, carboxy or N-piperidinocarbonyl "substituted aryl substituted C_1-10An alkyl group;

c which may be substituted by aryl_2-6An alkenyl group;

C_2-6a haloalkenyl group;

C_2-6an alkynyl group;

1, 1-dioxotetrahydrothienyl; or

An aryl group, a heteroaryl group,

R⁵is composed of

C_1-10An alkoxy group;

C_1-6a haloalkyl group;

may be selected from halogen atoms, C_3-10Cycloalkyl radical, C_2-6Alkoxycarbonyl group, C_1-6Haloalkyl, optionally substituted by "C_1-6Alkoxy or aryl radicals "Substituted C_1-6Alkoxy, optionally substituted by 1 to 2C_1-6Alkyl substituted C_3-10Cycloalkoxy, which may be selected from "C_1-6Alkyl radical, C_1-6Alkoxy radical, C_1-6Haloalkyl, C_1-6Aryl or aryloxy substituted with 1 to 5 groups of haloalkoxy, aralkyloxy, nitro and halogen atoms', heterocyclic group, phthalimido group, C_1-6Alkanoyloxy, aralkyloxy, C_1-6Alkylthio, arylthio and-N (R)⁶²)R⁷²(in the formula, R⁶²And R⁷²Each represents a hydrogen atom or C_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom) and 1 to 3 groups of the group represented by (A) and (B)_1-10Alkyl or C_{2- 6}An alkenyl group;

can be covered with C_1-6Alkyl radical, C_1-6Alkoxy radical, C_2-6Alkoxycarbonyl group, C_1-6Haloalkyl or C_1-6Haloalkoxy-substituted aryloxy; or

A group of the formula (II), B is C_3-10A cycloalkyl group, an aryl group or a heterocyclic group,

R⁵⁵and R⁵⁶Are respectively as

A hydrogen atom;

a halogen atom;

can be: an aryl, heterocyclic or aryloxy group which may be substituted by halogen atoms, or of the formula-N (R)⁶²)R⁷²(in the formula, R⁶²And R⁷²Each represents a hydrogen atom or C_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom) or a pharmaceutically acceptable salt thereof_1-10An alkyl group;

C_1-6a haloalkyl group;

C_1-10an alkoxy group;

C_1-6an alkylthio group;

C_1-6an alkylsulfonyl group;

can be covered with C_1-6Arylsulfonyl substituted with an alkyl group or a halogen atom;

C_1-6a haloalkoxy group;

C_1-6a haloalkylthio group;

C_3-10a cycloalkyl group;

C_2-6an alkenyl group;

C_2-6an alkenyloxy group;

C_2-6an alkenylthio group;

C_1-6alkoxy radical C_1-6An alkoxy group;

can be selected from C_1-6Alkyl radical, C_1-6Haloalkyl group, halogen atom, C_1-6Aryl substituted with 1 to 3 groups of alkoxy, cyano and nitro;

can be covered with C_1-6Alkyl or C_1-6A haloalkyl substituted heterocyclic group;

may be substituted by halogen atoms or C_1-6An alkyl-substituted aryloxy or arylthio group;

formula-N (R)⁶³)R⁷³(in the formula, R⁶³And R⁷³Each represents a hydrogen atom, C_1-6Alkyl radical, C_1-6Hydroxyalkyl radical, C_1-6Alkoxy radical C_1-6Alkyl, aryl, C_1-6Alkanoyl, di-C_1-6Alkylamino radical C_2-6Alkanoyl, benzoyl or can be substituted by C_1-6An alkyl-substituted heterocyclic group, or a group which represents a cyclic amino group bonded together with an adjacent nitrogen atom);

a hydroxyl group;

a cyano group;

a nitro group;

C_1-6an alkanoyl group;

C_1-6an alkanoyloxy group;

C_1-6alkanoyloxy group C_1-6An alkyl group;

C_2-6a haloalkanoyl group;

a carboxyl group;

C_2-6an alkoxycarbonyl group;

formula-CON (R)⁶⁴)R⁷⁴(in the formula, R⁶⁴And R⁷⁴Each represents a hydrogen atom, C_1-6Alkyl radical, C_1-6Alkoxy radical C_1-6Alkyl, or may be substituted by C_1-6An alkyl-substituted heterocyclic radical, or to an adjacent nitrogen atomGroups which together form a cyclic amino group),

R⁵⁷is a hydrogen atom, C_1-10Alkyl radical, C_1-6Haloalkyl, halogen atoms, or C_1-10An alkoxy imine compound or a pharmaceutically acceptable salt thereof as an active ingredient.

3. A cannabinoid receptor agonist comprising an imine compound represented by the formula (I-1) or a pharmaceutically acceptable salt thereof as an active ingredient,

[ in the formula, A¹Represents any one of rings represented by the following formulae (wherein X represents an oxygen atom or a sulfur atom),

R¹¹to represent

A hydrogen atom;

a halogen atom;

C_1-6an alkyl group;

C_2-6an alkenyl group;

C_1-6a haloalkyl group;

C_1-6an alkoxy group; or

formula-N (R)⁶)R⁷(in the formula, R⁶And R⁷Each represents a hydrogen atom or C_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom),

R²¹and R³¹Respectively represent

A hydrogen atom;

a halogen atom; or

C_1-6An alkyl group, a carboxyl group,

R⁴¹to represent

May be substituted by halogen atoms, C_3-10Cycloalkyl, aryl or C_1-6Alkoxy-substituted C_1-10Alkyl or C_2-6An alkenyl group, which is a radical of an alkenyl group,

R⁵¹to represent

C_1-6An alkoxy group;

C_1-6a haloalkyl group;

may be selected from halogen atoms, C_3-10Cycloalkyl, may be selected from "C_1-6Alkyl radical, C_1-6Alkoxy radical, C_1-6Aryl or aryloxy substituted with 1 to 5 groups of haloalkyl group and halogen atom' and C substituted with 1 to 3 groups of heterocyclic group_1-10Alkyl or C_2-6An alkenyl group;

a group represented by the formula (II-1),

{ wherein, B represents

C_3-10A cycloalkyl group;

an aryl group;

a heterocyclic group;

a fluorenyl group; or

A group represented by the formula (IV-1),

(in the formula, Y¹Is represented by- (CH)₂) p-or-O- (CH)₂) q-O-, p represents an integer of 2 to 4, q represents an integer of 1 to 3)

R⁵⁵¹And R⁵⁶¹Respectively represent

A hydrogen atom;

a halogen atom;

can be: an aryl, heterocyclic or aryloxy group which may be substituted by halogen atoms, or of the formula-N (R)⁶²)R⁷²(in the formula, R⁶²And R⁷²Each represents a hydrogen atom or C_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom) or a pharmaceutically acceptable salt thereof_1-10An alkyl group;

C_1-6a haloalkyl group;

C_1-10an alkoxy group;

C_1-6an alkylthio group;

C_1-6a haloalkoxy group;

C_3-10a cycloalkyl group;

C_2-6an alkenyl group;

can be selected from C_1-6Alkyl radical, C_1-6Haloalkyl group, halogen atom, C_1-6Aryl substituted with 1 to 3 groups of alkoxy and nitro;

can be covered with C_1-6An alkyl-substituted heterocyclic group;

aryloxy which may be substituted with halogen atom;

formula-N (R)⁶³⁴)R⁷³⁴(in the formula, R⁶³⁴And R⁷³⁴Each represents a hydrogen atom, C_1-6Alkyl, aryl or C_1-6Alkanoyl or a group which forms a cyclic amino group together with an adjacent nitrogen atom);

a hydroxyl group;

a cyano group;

a nitro group;

C_1-6an alkanoyl group;

C_2-6a haloalkanoyl group;

C_1-6an alkylsulfonyl group; or

Arylsulfonyl which may be substituted by a halogen atom,

R⁵⁷¹to represent

A hydrogen atom;

C_1-10an alkyl group;

C_1-10an alkoxy group; or

A halogen atom,

m represents an integer of 1 to 3, a and b each represent 0 or 1, W represents CO or SO₂。]

4. The cannabinoid receptor agonist comprising an imine compound or a pharmaceutically acceptable salt thereof as an active ingredient according to claim 3,

R⁵¹may be selected from halogen atoms, C_3-10Cycloalkyl radicals, optionally substituted by "C_1-6C substituted with 1 to 3 groups of aryl, thienyl and aryloxy substituted with haloalkyl and halogen atoms_1-10Alkyl or C_2-6Alkenyl, or formula (I)A group represented by I-1),

R⁵⁵¹is composed of

A hydrogen atom;

a halogen atom;

can be: c which may be substituted by an aryl, heterocyclic or aryloxy group substituted by halogen atoms_1-10An alkyl group;

C_1-6a haloalkyl group;

C_1-10an alkoxy group;

C_1-6a haloalkoxy group;

C_3-10a cycloalkyl group;

can be selected from C_1-6Alkyl group, halogen atom, C_1-6Aryl substituted with 1 to 3 groups of alkoxy and nitro;

can be covered with C_1-6An alkyl-substituted heterocyclic group;

aryloxy which may be substituted with halogen atom;

formula-N (R)⁶³¹)R⁷³¹(in the formula, R⁶³¹And R⁷³¹Each represents a hydrogen atom, C_1-6Alkyl, aryl or C_1-6Alkanoyl or a group which forms a cyclic amino group together with an adjacent nitrogen atom);

a cyano group;

C_1-6an alkanoyl group;

C_2-6a haloalkanoyl group; or

C_1-6An alkyl sulfonyl group, a carboxyl group,

R⁵⁶¹is composed of

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group;

C_1-6a haloalkyl group; or

C_1-10An alkoxy group,

R⁵⁷¹is composed of

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group; or

C_1-10An alkoxy group.

5. The cannabinoid receptor agonist comprising the imine compound or a pharmaceutically acceptable salt thereof as an active ingredient according to claim 3 or 4,

wherein A is¹Is a ring represented by the following formula.

6. The cannabinoid receptor agonist comprising an imine compound or a pharmaceutically acceptable salt thereof as an active ingredient according to claim 5,

R⁵¹to be can be C_3-10Cycloalkyl radicals, optionally substituted by "C_1-6Haloalkyl and halogen atoms "substituted aryl, thienyl or aryloxy substituted C_1-10An alkyl group or a group represented by the formula (II-1),

b is C_3-10A cycloalkyl group, an aryl group or a heterocyclic group,

R⁵⁵¹is composed of

A halogen atom;

C_1-10an alkyl group;

C_1-6a haloalkyl group;

C_1-10an alkoxy group;

C_1-6a haloalkoxy group;

C_3-10a cycloalkyl group;

can be selected from C_1-6Aryl substituted with 1 to 3 groups of alkyl and halogen atoms;

can be covered with C_1-6An alkyl-substituted heterocyclic group;

an aryloxy group;

morpholinyl;

an arylamino group;

a cyano group;

C_1-6an alkanoyl group;

C_2-6a haloalkanoyl group; or

C_1-6An alkyl sulfonyl group, a carboxyl group,

R⁵⁶¹is composed of

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group;

C_1-6a haloalkyl group; or

C_1-10An alkoxy group,

R⁵⁷¹is composed of

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group; or

C_1-10An alkoxy group.

7. The cannabinoid receptor agonist comprising an imine compound or a pharmaceutically acceptable salt thereof as an active ingredient according to claim 6,

R⁵¹is a group represented by the formula (II-1),

b is a phenyl group, and B is a phenyl group,

R⁵⁵¹is composed of

A halogen atom;

C_1-10an alkyl group;

C_1-6a haloalkyl group;

C_1-6an alkoxy group;

C_1-6a haloalkoxy group;

C_3-10a cycloalkyl group;

an aryl group;

an aryloxy group;

morpholinyl;

an arylamino group;

a cyano group;

C_1-6an alkanoyl group;

C_2-6a haloalkanoyl group;

or C_1-6An alkyl sulfonyl group, a carboxyl group,

R⁵⁶¹is composed of

A hydrogen atom;

a halogen atom;

C_1-6a haloalkyl group;

or C_1-6An alkoxy group,

R⁵⁷¹is composed of

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group; or

C_1-10Alkoxy (wherein, R⁵⁵¹、R⁵⁷¹And R⁴¹When it is an alkyl group, R⁵⁵¹And R⁵⁷¹Has 1 to 6 carbon atoms, R⁴¹Has 2 to 10 carbon atoms) and m is 1.

8. The cannabinoid receptor agonist according to any of claims 1 to 7, which is a cannabinoid type 1 receptor agonist or a cannabinoid type 2 receptor agonist.

9. The cannabinoid receptor agonist according to any of claims 1 to 7, which is a therapeutic or prophylactic agent for pain.

10. The cannabinoid receptor agonist according to any of claims 1 to 7, which is a therapeutic agent or a prophylactic agent for autoimmune diseases.

11. An imine compound represented by the formula (I-1) or a pharmaceutically acceptable salt thereof.

[ in the formula, A¹Represents any one of rings represented by the following formulae (wherein X represents an oxygen atom or a sulfur atom),

R¹¹to represent

A hydrogen atom;

a halogen atom;

C_1-6an alkyl group;

C_2-6an alkenyl group;

C_1-6a haloalkyl group;

C_1-6an alkoxy group; or

formula-N (R)⁶)R⁷(in the formula, R⁶And R⁷Each represents a hydrogen atom or C_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom),

R²¹and R³¹Respectively represent

A hydrogen atom;

a halogen atom; or

C_1-6An alkyl group, a carboxyl group,

R⁴¹to represent

May be substituted by halogen atoms, C_3-10Cycloalkyl, aryl or C_1-6Alkoxy-substituted C_1-10Alkyl or C_2-6An alkenyl group, which is a radical of an alkenyl group,

R⁵¹to represent

C_1-6An alkoxy group;

C_1-6a haloalkyl group;

may be selected from halogen atoms, C_3-10Cycloalkyl, may be selected from "C_1-6Alkyl radical, C_1-6Alkoxy radical, C_1-6Aryl or aryloxy substituted with 1 to 5 groups of haloalkyl group and halogen atom' and C substituted with 1 to 3 groups of heterocyclic group_1-10Alkyl or C_2-6An alkenyl group;

a group represented by the formula (II-1),

{ wherein, B represents

C_3-10A cycloalkyl group;

an aryl group;

a heterocyclic group;

a fluorenyl group; or

A group represented by the formula (IV-1),

(in the formula, Y¹Is represented by- (CH)₂) p-or-O- (CH)₂) q-O-, p represents an integer of 2 to 4, q represents an integer of 1 to 3)

R⁵⁵¹And R⁵⁶¹Respectively represent

A hydrogen atom;

a halogen atom;

can be: an aryl, heterocyclic or aryloxy group which may be substituted by halogen atoms, or of the formula-N (R)⁶²)R⁷²(in the formula, R⁶²And R⁷²Each represents a hydrogen atom or C_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom) or a pharmaceutically acceptable salt thereof_1-10An alkyl group;

C_1-6a haloalkyl group;

C_1-10an alkoxy group;

C_1-6an alkylthio group;

C_1-6a haloalkoxy group;

C_3-10a cycloalkyl group;

C_2-6an alkenyl group;

can be selected from C_1-6Alkyl radical, C_1-6Haloalkyl group, halogen atom, C_1-6Aryl substituted with 1 to 3 groups of alkoxy and nitro;

can be covered with C_1-6An alkyl-substituted heterocyclic group;

aryloxy which may be substituted with halogen atom;

formula-N (R)⁶³⁴)R⁷³⁴(in the formula, R⁶³⁴And R⁷³⁴Each represents a hydrogen atom, C_1-6Alkyl, aryl or C_1-6Alkanoyl or a group which forms a cyclic amino group together with an adjacent nitrogen atom);

a hydroxyl group;

a cyano group;

a nitro group;

C_1-6an alkanoyl group;

C_2-6a haloalkanoyl group;

C_1-6an alkylsulfonyl group; or

Arylsulfonyl which may be substituted by a halogen atom,

R⁵⁷¹to represent

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group; or

C_1-10An alkoxy group,

m represents an integer of 1 to 3, a and b each represent 0 or 1, W represents CO or SO₂]

12. The imine compound according to claim 11 or a pharmaceutically acceptable salt thereof,

R⁵¹may be selected from halogen atoms, C_3-10Cycloalkyl radicals, optionally substituted by "C_1-6C substituted with 1 to 3 groups of aryl, thienyl and aryloxy substituted with haloalkyl and halogen atoms_1-10Alkyl or C_2-6An alkenyl group, or a group represented by the formula (II-1),

R⁵⁵¹is composed of

A hydrogen atom;

a halogen atom;

can be: c which may be substituted by an aryl, heterocyclic or aryloxy group substituted by halogen atoms_1-10An alkyl group;

C_1-6a haloalkyl group;

C_1-10an alkoxy group;

C_1-6a haloalkoxy group;

C_3-10a cycloalkyl group;

can be selected from C_1-6Alkyl group, halogen atom, C_1-6Aryl substituted with 1 to 3 groups of alkoxy and nitro;

can be covered with C_1-6An alkyl-substituted heterocyclic group;

aryloxy which may be substituted with halogen atom;

formula-N (R)⁶³¹)R⁷³¹(in the formula, R⁶³¹And R⁷³¹Each represents a hydrogen atom, C_1-6Alkyl, aryl or C_1-6Alkanoyl or a group which forms a cyclic amino group together with an adjacent nitrogen atom);

a cyano group;

C_1-6an alkanoyl group;

C_2-6a haloalkanoyl group; or

C_1-6An alkyl sulfonyl group, a carboxyl group,

R⁵⁶¹is composed of

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group;

C_1-6a haloalkyl group; or

C_1-10An alkoxy group,

R⁵⁷¹is composed of

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group; or

C_1-10An alkoxy group.

13. The imine compound according to claim 11 or 12, or a pharmaceutically acceptable salt thereof, wherein W is-CO-.

14. The imine compound according to claim 13, or a pharmaceutically acceptable salt thereof, R⁴¹Is C_1-6Alkoxy-or aryl-substituted C_1-10Alkyl radical, R⁵⁵¹Is C_1-6Haloalkyl, R⁵⁶⁴Is a halogen atom.

15. The imine compound according to claim 13, or a pharmaceutically acceptable salt thereof, R⁴¹Is C_3-10Cycloalkyl or C_1-6Alkoxy-substituted C_1-10An alkyl group.

16. The imine compound according to claim 14 or 15, or a pharmaceutically acceptable salt thereof, A¹Is a 1, 2-dihydropyridine ring.

17. The imine compound of claim 16, or a pharmaceutically acceptable salt thereof, R⁵¹To be can be C_3-10Cycloalkyl radicals, optionally substituted by "C_1-6Haloalkyl and halogen atoms "substituted aryl, thienyl or aryloxy substituted C_1-10An alkyl group or a group represented by the formula (II-1),

b is C_3-10A cycloalkyl group, an aryl group or a heterocyclic group,

R⁵⁵¹is composed of

A halogen atom;

C_1-10an alkyl group;

C_1-6a haloalkyl group;

C_1-10an alkoxy group;

C_1-6a haloalkoxy group;

C_3-10a cycloalkyl group;

can be selected from C_1-6Aryl substituted with 1 to 3 groups of alkyl and halogen atoms;

can be covered with C_1-6An alkyl-substituted heterocyclic group;

an aryloxy group;

morpholinyl;

an arylamino group;

a cyano group;

C_1-6an alkanoyl group;

C_2-6a haloalkanoyl group; or

C_1-6An alkyl sulfonyl group, a carboxyl group,

R⁵⁶¹is composed of

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group;

C_1-6a haloalkyl group; or

C_1-10An alkoxy group,

R⁵⁷¹is composed of

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group; or

C_1-10An alkoxy group.

18. The imine compound according to claim 17 or a pharmaceutically acceptable salt thereof,

R⁵¹is a group represented by the formula (II-1),

b is a phenyl group, and B is a phenyl group,

R⁵⁵¹is composed of

A halogen atom;

C_1-10an alkyl group;

C_1-6a haloalkyl group;

C_1-6an alkoxy group;

C_1-6a haloalkoxy group;

C_3-10a cycloalkyl group;

an aryl group;

an aryloxy group;

morpholinyl;

an arylamino group;

a cyano group;

C_1-6an alkanoyl group;

C_2-6a haloalkanoyl group;

or C_1-6An alkyl sulfonyl group, a carboxyl group,

R⁵⁶¹is composed of

A hydrogen atom;

a halogen atom;

C_1-6a haloalkyl group;

or C_1-6An alkoxy group,

R⁵⁷¹is composed of

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group; or

C_1-10Alkoxy, m is 1.

19. The imine compound of claim 18, or a pharmaceutically acceptable salt thereof, R⁴¹Is C_3-10Cycloalkyl-substituted C_1-10An alkyl group.

20. The imine compound of claim 19, or a pharmaceutically acceptable salt thereof, R⁵¹Is selected from halogen atoms, C_1-10Alkyl radical, C_1-6Haloalkyl, C_1-10Alkoxy, cyano and C_1-6Phenyl substituted with 1 to 3 groups of haloalkoxy.

21. The imine compound according to any one of claims 13 to 20, wherein the steric configuration of the double bond formed between the carbon atom and the nitrogen atom of the group represented by > C ═ N-CO-, in formula (I-1), is the (Z) configuration, or a pharmaceutically acceptable salt thereof.

22. A cannabinoid receptor agonist comprising an imine compound represented by the formula (I-2) or a pharmaceutically acceptable salt thereof as an active ingredient.

[ in the formula, R¹²And R²²Respectively represent

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group;

C_1-6a haloalkyl group;

C_1-6an alkoxy group;

a carboxyl group;

C_2-6an alkoxycarbonyl group;

hydroxy radical C_1-6An alkyl group;

aryl which may be substituted with 1 to 3 halogen atoms; or

formula-CON (R)⁶¹)R⁷¹(in the formula, R⁶¹And R⁷¹Each represents a hydrogen atom or C which may be substituted by a cyclic amino group_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom), or R¹¹And R²²Taken together with adjacent carbon atoms to form a radical which may be substituted by C_1-6Alkyl or halogen atom substituted benzene ring, pyridine ring or cyclohexene ring,

R⁴²to represent

May be substituted by halogen atoms, cyano groups, carboxyl groups, C_2-6Alkoxycarbonyl group, C_3-10Cycloalkyl radicals, optionally substituted by "C_1-6Haloalkyl, C_1-6Haloalkoxy, C_1-6Haloalkylthio, carboxy, C_2-6Alkoxycarbonyl-or piperidinocarbonyl-substituted aryl, arylthio, C_1-6Alkoxy or of the formula-CON (R)⁶²)R⁷²(in the formula, R⁶²And R⁷²Each represents a hydrogen atom or C_1-6Alkyl, or a group which forms a cyclic amino group together with the adjacent nitrogen atom) is substitutedC_1-10Alkyl or C_2-6An alkenyl group; or

C_2-6An alkynyl group,

R⁵²to represent

A hydrogen atom;

C_1-6an alkoxy group;

C_1-6a haloalkyl group;

may be selected from halogen atoms, C_3-10Cycloalkyl radical, C_2-6Alkoxycarbonyl, can be substituted by "C_1-6Alkoxy or aryl "substituted C_1-6Alkoxy radical, may be substituted by C_1-6Alkyl substituted C_3-10Cycloalkoxy, which may be selected from "C_1-6Alkyl radical, C_1-6Haloalkyl, C_1-6Aryl or aryloxy substituted with 1 to 5 groups of alkoxy, aralkyloxy, nitro and halogen atoms', heterocyclic group, phthalimido group, C_1-6Alkanoyloxy, aralkyloxy, C_1-6Alkylthio, arylthio and-N (R)⁶²)R⁷²(in the formula, R⁶²And R⁷²Each represents a hydrogen atom or C_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom) and 1 to 3 groups of the group represented by (A) and (B)_1-10Alkyl or C_2-6An alkenyl group;

can be covered with C_1-6Alkyl radical, C_1-6Alkoxy radical, C_2-6Alkoxycarbonyl or C_1-6Haloalkyl-substituted aryloxy;

an aralkyloxy group;

a group represented by the formula (II-2),

{ wherein, B represents

C_3-10A cycloalkyl group;

an aryl group;

a heterocyclic group;

C_2-6a cyclic amino group;

a fluorenyl group;

2-oxopyrrolidinyl;

a group represented by the formula (III);

(wherein n represents 0 or 1)

Or a group represented by the formula (IV-2),

(in the formula, Y²Is represented by- (CH)₂)p-、-CO-CH₂-CH₂-、-O-CH₂-CH ═ CH-or-O- (CH)₂) q-O-, p represents an integer of 2 to 4, q represents an integer of 1 to 3),

R⁵⁵²to represent

A hydrogen atom;

a halogen atom;

can be: aryl which may be substituted by halogen atoms, aryloxy or a compound of formula-N (R)⁶²)R⁷²(in the formula, R⁶²And R⁷²Each represents a hydrogen atom or C_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom) or a pharmaceutically acceptable salt thereof_1-10An alkyl group;

C_1-6a haloalkyl group;

C_1-10an alkoxy group;

C_1-6an alkylthio group;

C_1-6an alkylsulfonyl group;

can be covered with C_1-6An arylthio group substituted with an alkyl group or a halogen atom;

can be covered with C_1-6Arylsulfonyl substituted with an alkyl group or a halogen atom;

C_1-6a haloalkoxy group;

C_1-6a haloalkylthio group;

C_3-10a cycloalkyl group;

C_2-6an alkenyl group;

C_1-6alkoxy radical C_1-6An alkoxy group;

can be selected from C_1-6Alkyl radical, C_1-6Haloalkyl, halogenAtom, C_1-6Aryl substituted with 1 to 3 groups of alkoxy and nitro;

can be covered with C_1-6Alkyl or C_1-6A haloalkyl substituted heterocyclic group;

aryloxy which may be substituted with halogen atom;

formula-N (R)⁶³)R⁷³(in the formula, R⁶³And R⁷³Each represents a hydrogen atom, C_1-6Alkyl radical, C_1-6Hydroxyalkyl radical, C_1-6Alkoxy radical C_1-6Alkyl, aryl, C_1-6Alkanoyl or benzoyl, or a group which is linked to an adjacent nitrogen atom to form a cyclic amino group);

a hydroxyl group;

a cyano group;

a nitro group;

a carboxyl group;

C_2-6an alkoxycarbonyl group;

c which may be substituted by aralkyl or aryl_2-6A cyclic amino group;

formula-CON (R)⁶⁴)R⁷⁴(in the formula, R⁶⁴And R⁷⁴Each represents a hydrogen atom, C_1-6Alkyl radical, C_1-6Alkoxy radical C_1-6Alkyl, or may be substituted by C_1-6An alkyl-substituted heterocyclic group, or a group which represents a cyclic amino group bonded together with an adjacent nitrogen atom);

formula-SO₂N(R⁶²)R⁷²(in the formula, R⁶²And R⁷²Each represents a hydrogen atom or C_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom);

c which may be substituted by halogen atoms_1-6An alkylsulfonyl group;

arylsulfonyl which may be substituted by a halogen atom; or

2-oxa-3-oxobicyclo [2.2.1] heptyl,

R⁵⁶²to represent

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group;

C_1-6a haloalkyl group; or

C_1-6An alkoxy group,

R⁵⁷²to represent

A hydrogen atom;

C_1-10an alkyl group;

C_1-6a haloalkyl group;

a halogen atom; or

C_1-6An alkoxy group,

m represents an integer of 1 to 3, X represents an oxygen atom or a sulfur atom, and W represents CO or SO₂。]

23. The cannabinoid receptor agonist comprising an imine compound or a pharmaceutically acceptable salt thereof as an active ingredient according to claim 22, wherein X is a sulfur atom.

24. The cannabinoid receptor agonist comprising an imine compound or a pharmaceutically acceptable salt thereof as an active ingredient according to claim 23,

R¹²is a hydrogen atom, a halogen atom, C_1-10Alkyl, carboxyl, C_2-6Alkoxycarbonyl of the formula-CON (R)⁶¹)R⁷¹(in the formula, R⁶¹And R⁷¹Each represents a hydrogen atom or C which may be substituted by a cyclic amino group_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom) or an aryl group,

R²²is a hydrogen atom, C_1-10Alkyl radical, C_1-6Haloalkyl or aryl, or is R¹¹And R²²Taken together with adjacent carbon atoms to form a radical which may be substituted by C_1-6Alkyl or halogen atom substituted benzene ring, pyridine ring or cyclohexene ring.

25. The cannabinoid receptor agonist comprising an imine compound or a pharmaceutically acceptable salt thereof as an active ingredient according to claim 24,

R⁴²is optionally substituted by halogen atom, cyano group, carboxyl group, C_2-6An alkoxycarbonyl group,C_3-10Cycloalkyl radicals, optionally substituted by "C_1-6Haloalkylthio, carboxy or C_2-6Alkoxycarbonyl-substituted aryl, arylthio, C_1-6Alkoxy or of the formula-CON (R)⁶²)R⁷²(in the formula, R⁶²And R⁷²Each represents a hydrogen atom or C_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom) or a pharmaceutically acceptable salt thereof_1-10Alkyl or C_2-6An alkenyl group; or

C_2-6An alkynyl group,

R⁵²is composed of

C_1-6An alkoxy group;

C_1-6a haloalkyl group;

can be selected from C_3-10Cycloalkyl radical, C_2-6Alkoxycarbonyl group, C_1-6Alkoxy, may be selected from "C_1-6Alkyl radical, C_1-6Haloalkyl, C_1-6Aryl or aryloxy substituted with 1 to 5 groups of alkoxy, aralkyloxy, nitro and halogen atoms ", heterocyclic group, C_1-6Alkylthio, arylthio and-N (R)⁶²)R⁷²(in the formula, R⁶²And R⁷²Each represents a hydrogen atom or C_1-6Alkyl or a group which forms a cyclic amino group together with an adjacent nitrogen atom) and C substituted with 1 to 3 groups_1-10Alkyl or C_2-6An alkenyl group;

can be covered with C_1-6Alkoxy radical, C_2-6Alkoxycarbonyl or C_1-6Haloalkyl-substituted aryloxy; or

A group represented by the formula (II),

b is

C_3-10A cycloalkyl group;

an aryl group; or

A heterocyclic group,

R⁵⁵²is composed of

A hydrogen atom;

a halogen atom;

may be aryl, or of the formula-N (R)⁶²)R⁷²(in the formula, R⁶²And R⁷²Each represents a hydrogen atom or C_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom) or a pharmaceutically acceptable salt thereof_1-10An alkyl group;

C_1-6a haloalkyl group;

C_1-10an alkoxy group;

C_1-6an alkylthio group;

C_1-6an alkylsulfonyl group;

an arylthio group;

arylsulfonyl which may be substituted by a halogen atom;

C_1-6a haloalkoxy group;

C_1-6a haloalkylthio group;

C_1-6alkoxy radical C_1-6An alkoxy group;

can be selected from C_1-6Aryl substituted with 1 to 3 groups of haloalkyl, halogen atom and nitro;

can be covered with C_1-6A haloalkyl substituted heterocyclic group;

aryloxy which may be substituted with halogen atom;

formula-N (R)⁶³)R⁷³(in the formula, R⁶³And R⁷³Each represents a hydrogen atom, C_1-6Alkyl radical, C_1-6Hydroxyalkyl radical, C_1-6Alkoxy radical C_1-6Alkyl, or benzoyl, or a group which is linked to the adjacent nitrogen atom to form a cyclic amino group);

a hydroxyl group;

a cyano group;

a nitro group;

a carboxyl group;

C_2-6an alkoxycarbonyl group;

formula-CON (R)⁶⁴)R⁷⁴(in the formula, R⁶⁴And R⁷⁴Each represents a hydrogen atom, C_1-6Alkyl radical, C_1-6Alkoxy radical C_1-6Alkyl, or may be substituted by C_1-6An alkyl-substituted heterocyclic group, or a group which represents a cyclic amino group bonded together with an adjacent nitrogen atom),

R⁵⁶²is composed of

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group;

C_1-6a haloalkyl group; or

C_1-10An alkoxy group,

R⁵⁷²is composed of

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group; or

C_1-6An alkoxy group.

26. The cannabinoid receptor agonist comprising an imine compound or a pharmaceutically acceptable salt thereof as an active ingredient according to claim 25,

R⁵²is a group represented by the formula (II-2), B is phenyl or pyridyl, R⁵⁵²Is composed of

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group;

C_1-6a haloalkyl group; or

C_1-10An alkoxy group,

R⁵⁶²is composed of

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group; or

C_1-6An alkoxy group,

R⁵⁷²is composed of

A hydrogen atom;

a halogen atom; or

C_1-6An alkoxy group.

27. The cannabinoid receptor agonist comprising an imine compound or a pharmaceutically acceptable salt thereof as an active ingredient according to claim 26,

R⁴²is optionally substituted by halogen atom, cyano group, carboxyl group, C_2-6Alkoxycarbonyl group, C_3-10Cycloalkyl radicals, optionally substituted by "C_1-6Haloalkylthio, carboxy or C_2-6Alkoxycarbonyl-substituted aryl, arylthio, C_1-6Alkoxy or of the formula-CON (R)⁶²)R⁷²(in the formula, R⁶²And R⁷²Each represents a hydrogen atom or C_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom) or a pharmaceutically acceptable salt thereof_1-10An alkyl group.

28. The cannabinoid receptor agonist according to any of claims 22 to 27, being a cannabinoid type 1 receptor agonist or a cannabinoid type 2 receptor agonist.

29. The cannabinoid receptor agonist according to any of claims 22 to 27, being a therapeutic or prophylactic agent for pain.

30. The cannabinoid receptor agonist according to any of claims 22 to 27, which is a therapeutic agent or a prophylactic agent for autoimmune diseases.

31. An imine compound or a pharmaceutically acceptable salt thereof, represented by the following formula (I-2),

w is the radical of CO,

R¹²is composed of

A halogen atom;

C_1-6an alkyl group;

C_1-6a haloalkyl group;

C_1-6an alkoxy group;

a carboxyl group;

C_2-6an alkoxycarbonyl group;

hydroxy radical C_1-6An alkyl group;

aryl which may be substituted with 1 to 3 halogen atoms; or

formula-CON (R)⁶¹)R⁷¹(in the formula, R⁶¹And R⁷¹Each represents a hydrogen atom or may be substituted by a cyclic amino groupC of (A)_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom),

R²²is composed of

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group;

C_1-6a haloalkyl group; or

Aryl or is R¹²And R²²Taken together with adjacent carbon atoms to form a radical which may be substituted by C_1-6Alkyl or halogen atom substituted benzene ring, pyridine ring or cyclohexene ring,

R⁴²is C_3-10Cycloalkyl or C_1-6Alkoxy-substituted C_1-10Alkyl or C_2-6An alkenyl group, which is a radical of an alkenyl group,

x and R⁵²The same as above.

32. The imine compound according to claim 31, or a pharmaceutically acceptable salt thereof, wherein X is a sulfur atom.

33. The imine compound of claim 32, or a pharmaceutically acceptable salt thereof, R¹²Is a halogen atom or C_1-10Alkyl radical, R²²Is C_1-10Alkyl or C_1-6A haloalkyl group.

34. The imine compound according to claim 33 or a pharmaceutically acceptable salt thereof,

R⁵²is composed of

C_1-6An alkoxy group;

C_1-6a haloalkyl group;

can be selected from C_3-10Cycloalkyl radical, C_2-6Alkoxycarbonyl group, C_1-6Alkoxy, may be selected from "C_1-6Alkyl radical, C_1-6Haloalkyl, C_1-6Aryl or aryloxy substituted with 1 to 5 groups of alkoxy, aralkyloxy, nitro and halogen atom', heterocyclic group, C_1-6Alkylthio, arylthio and-N (R)⁶²)R⁷²(in the formula，R⁶²And R⁷²Each represents a hydrogen atom or C_1-6Alkyl or a group which forms a cyclic amino group together with an adjacent nitrogen atom) and C substituted with 1 to 3 groups_1-10Alkyl or C_2-6An alkenyl group;

can be covered with C_1-6Alkoxy radical, C_2-6Alkoxycarbonyl or C_1-6Haloalkyl-substituted aryloxy; or

A group represented by the formula (II-2),

b is

C_3-10A cycloalkyl group;

an aryl group;

a heterocyclic group,

R⁵⁵²is composed of

A hydrogen atom;

a halogen atom;

may be aryl or of the formula-N (R)⁶²)R⁷²(in the formula, R⁶²And R⁷²Each represents a hydrogen atom or C_1-6Alkyl, or a group which forms a cyclic amino group together with an adjacent nitrogen atom) or a pharmaceutically acceptable salt thereof_1-10An alkyl group;

C_1-6a haloalkyl group;

C_1-10an alkoxy group;

C_1-6an alkylthio group;

C_1-6an alkylsulfonyl group;

an arylthio group;

arylsulfonyl which may be substituted by a halogen atom;

C_1-6a haloalkoxy group;

C_1-6a haloalkylthio group;

C_1-6alkoxy radical C_1-6An alkoxy group;

can be selected from C_1-6Aryl substituted with 1 to 3 groups of haloalkyl, halogen atom and nitro;

can be covered with C_1-6A haloalkyl substituted heterocyclic group;

aryloxy which may be substituted with halogen atom;

a hydroxyl group;

a cyano group;

a nitro group;

a carboxyl group; or

C_2-6An alkoxycarbonyl group, a carbonyl group,

R⁵⁶²is composed of

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group;

C_1-10an alkoxy group,

R⁵⁷²is composed of

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group; or

C_1-10An alkoxy group.

35. The imine compound according to claim 34 or a pharmaceutically acceptable salt thereof,

R⁵²is a group represented by the formula (II-2), B is phenyl or pyridyl, R⁵⁵²Is composed of

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group;

C_1-6a haloalkyl group;

C_1-10an alkoxy group; or

C_1-6A halogenated alkoxy group,

R⁵⁶²is composed of

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group;

C_1-10an alkoxy group,

R⁵⁷²is composed of

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group; or

C_1-10An alkoxy group.

36. The imine compound according to any one of claims 31 to 35, wherein the steric configuration of the double bond of the group represented by > C ═ N — CO "in formula (I-2) is the (Z) configuration, or a pharmaceutically acceptable salt thereof.

37. A cannabinoid receptor agonist comprising an imine compound represented by the formula (I-3) or a pharmaceutically acceptable salt thereof as an active ingredient.

[ in the formula, the dotted line indicates that any one of them is a double bond,

X³represents C (R)¹³) The oxygen content of the oxygen-containing gas is S or O,

R¹³、R²³and R³³Respectively represent

A hydrogen atom;

c which may be substituted by aryl groups substituted by halogen atoms_1-10An alkyl group;

C_1-6a haloalkyl group;

C_3-10a cycloalkyl group; or

Aryl or aralkyl which may be substituted by 1 to 3 halogen atoms, or X³Is C (R)¹³) When R is¹³And R²³Taken together to represent-CH₂-S-CH₂A group represented by (wherein, X³When is S or O, R³³Is unsubstituted) is used,

R⁴³to represent

1, 1-dioxotetrahydrothienyl;

can be selected from C_3-10Cycloalkyl radical, C_1-6Haloalkyl and C_1-6C substituted by radicals of alkoxy_1-10Alkyl or C_2-6An alkenyl group; or an aromatic group, or a salt thereof,

R⁵³to represent

A hydrogen atom;

C_1-10an alkoxy group;

C_1-6alkoxy radical C_1-6An alkoxy group;

C_1-6a haloalkyl group;

can be selected from C_1-6Alkoxy radical, C_3-10Cycloalkyl radical, C_2-6Alkoxycarbonyl, can be selected from "C_1-61 to 5 alkoxy groups and halogen atoms ″)Radical-substituted aryl or aryloxy radicals, heterocyclic radicals, C_1-6Alkanoyloxy, aralkyloxy and C_1-6C substituted by 1-3 groups in alkylthio group_1-10Alkyl or C_2-6An alkenyl group;

a group represented by the formula (II-3),

{ wherein, B represents

C_3-10A cycloalkyl group;

an aryl group;

a heterocyclic group;

C_2-6a cyclic amino group;

a group represented by the formula (III);

(wherein n represents 0 or 1.)

Or a group represented by the formula (IV-3),

(in the formula, Y³represents-O-CH₂-CH ═ CH-or-O- (CH)₂) q-O-, q represents an integer of 1 to 3)

R⁵⁵³To represent

A hydrogen atom;

a halogen atom;

an aryl group;

C_1-10an alkyl group;

C_1-6alkanoyloxy group C_1-6An alkyl group;

C_1-6a haloalkyl group;

C_1-10an alkoxy group;

C_1-6an alkylthio group;

C_2-6an alkenyloxy group;

C_2-6an alkenylthio group;

C_1-6a haloalkoxy group;

C_1-6a haloalkylthio group;

aryl which may be substituted with 1 to 3 halogen atoms or cyano;

a heterocyclic group;

may be substituted by halogen atoms or C_1-6An alkyl-substituted aryloxy or arylthio group;

formula-N (R)⁶³³)R⁷³³(in the formula, R⁶³³And R⁷³³Each represents a hydrogen atom, C_1-6Alkyl radical, C_1-6Alkanoyl, di-C_1-6Alkylamino radical C_2-6Alkanoyl or may be substituted by C_1-6An alkyl-substituted heterocyclic group, or a group which represents a cyclic amino group bonded together with an adjacent nitrogen atom);

a cyano group;

a nitro group;

C_2-6an alkoxycarbonyl group;

R⁵⁶³to represent

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group; or

C_1-6A halogenated alkyl group,

R⁵⁷³to represent

A hydrogen atom;

C_1-10an alkyl group;

a halogen atom; or

C_1-10An alkoxy group,

m represents an integer of 1 to 3, W represents-CO-, -CO-NH-, -CS-NH-or-SO₂-。]

38. The cannabinoid receptor agonist comprising an imine compound or a pharmaceutically acceptable salt thereof as an active ingredient according to claim 37,

R¹³is a hydrogen atom or a phenyl group, R²³And R³³Are respectively C_1-6Alkyl radical, C_1-6Haloalkyl or C_3-10A cycloalkyl group,

R⁴³is composed of

Can be selected from C_3-10Cycloalkyl radical, C_1-6Haloalkyl and C_1-6Alkoxy radicalC substituted by a group of_1-10An alkyl group, a carboxyl group,

R⁵³is composed of

C_1-10An alkoxy group;

C_1-6alkoxy radical C_1-6An alkoxy group;

C_1-6a haloalkyl group;

can be selected from C_1-6Alkoxy radical, C_3-10Cycloalkyl radical, C_2-6Alkoxycarbonyl, can be selected from "C_1-6Aryl or aryloxy group substituted with 1 to 5 groups of alkoxy group and halogen atom ", heterocyclic group, C_1-6Alkanoyloxy, aralkyloxy and C_1-6C substituted by 1-3 groups in alkylthio group_1-10Alkyl or C_2-6An alkenyl group; or

A group represented by the formula (II-3),

b is aryl, furyl, thienyl, pyrazolyl, isoxazolyl, pyridyl, a group represented by the formula (III) or a group represented by the formula (IV-3).

39. The cannabinoid receptor agonist comprising an imine compound or a pharmaceutically acceptable salt thereof as an active ingredient according to claim 38, wherein W is-CO-.

40. The cannabinoid receptor agonist comprising an imine compound or a pharmaceutically acceptable salt thereof as an active ingredient according to claim 39,

X³is C (R)¹³)，

R⁵³Is composed of

C_1-10An alkoxy group;

C_1-6a haloalkyl group;

can be selected from C_1-6Alkoxy radical, C_3-10Cycloalkyl and may be selected from "C_1-6Alkoxy and halogen atom' 1-5 groups substituted aryl group 1-3 groups substituted C_1-10An alkyl group; or

A group represented by the formula (II-3), B is a phenyl group.

41. The cannabinoid receptor agonist comprising an imine compound or a pharmaceutically acceptable salt thereof as an active ingredient according to claim 40,

R⁵⁵³is composed of

A halogen atom;

C_1-10an alkyl group;

C_1-6a haloalkyl group;

C_1-10an alkoxy group;

C_1-6a haloalkoxy group;

aryl which may be substituted with 1 to 3 halogen atoms;

aryloxy which may be substituted with halogen atom;

formula-N (R)⁶³³)R⁷³³(in the formula, R⁶³³And R⁷³³Each represents a hydrogen atom or C_1-6Alkyl) group;

a cyano group;

a nitro group; or

C_2-6An alkoxycarbonyl group, a carbonyl group,

R⁵⁶³is composed of

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group;

C_1-6an alkoxy group; or

C_1-6A halogenated alkyl group,

R⁵⁷³is composed of

A hydrogen atom;

C_1-10an alkyl group;

a halogen atom; or

C_1-10An alkoxy group.

42. The cannabinoid receptor agonist comprising an imine compound or a pharmaceutically acceptable salt thereof as an active ingredient according to claim 39,

X³is a sulfur atom, R⁵³Is a group represented by the formula (II-3), and B is a phenyl group.

43. The cannabinoid receptor agonist comprising an imine compound or a pharmaceutically acceptable salt thereof as an active ingredient according to claim 42,

R⁵⁵³is composed of

A halogen atom;

C_1-10an alkyl group;

C_1-6a haloalkyl group; or

C_1-10An alkoxy group,

R⁵⁶³is composed of

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group;

C_1-6an alkoxy group; or

C_1-6A halogenated alkyl group,

R⁵⁷³is a hydrogen atom.

44. The cannabinoid receptor agonist comprising, as an active ingredient, an imine compound or a pharmaceutically acceptable salt thereof according to claim 41 or 43, wherein R is⁴³Is C_3-10Cycloalkyl-substituted C_1-10An alkyl group.

45. The cannabinoid receptor agonist according to any of claims 37 to 44, being a cannabinoid type 1 receptor agonist or a cannabinoid type 2 receptor agonist.

46. The cannabinoid receptor agonist according to any of claims 37 to 44, being a therapeutic or prophylactic agent for pain.

47. The cannabinoid receptor agonist according to any of claims 37 to 44, which is a therapeutic agent or a prophylactic agent for autoimmune diseases.

48. An imine compound represented by the formula (I-3) or a pharmaceutically acceptable salt thereof.

[ in the formula, the dotted line represents that any one of them is a double bond,

X³represents C (R)¹³) The oxygen content of the oxygen-containing gas is S or O,

R¹³、R²³and R³³Respectively represent

A hydrogen atom;

c which may be substituted by aryl groups substituted by halogen atoms_1-10An alkyl group;

C_1-6a haloalkyl group;

C_3-10a cycloalkyl group; or

Aryl or aralkyl which may be substituted by 1 to 3 halogen atoms, or X³Is C (R)¹³) When R is¹³And R²³Taken together to represent-CH₂-S-CH₂A group represented by (wherein, X³When is S or O, R³³Is unsubstituted) is used,

R⁴³to represent

1, 1-dioxotetrahydrothienyl;

can be selected from C_3-10Cycloalkyl radical, C_1-6Haloalkyl and C_1-6C substituted by radicals of alkoxy_1-10Alkyl or C_2-6An alkenyl group; or an aromatic group, or a salt thereof,

R⁵³to represent

A hydrogen atom;

C_1-10an alkoxy group;

C_1-6alkoxy radical C_1-6An alkoxy group;

C_1-6a haloalkyl group;

can be selected from C_1-6Alkoxy radical, C_3-10Cycloalkyl radical, C_2-6Alkoxycarbonyl, can be selected from "C_1-6Aryl or aryloxy group substituted with 1 to 5 groups of alkoxy group and halogen atom ", heterocyclic group, C_1-6Alkanoyloxy, aralkyloxy and C_1-6C substituted by 1-3 groups in alkylthio group_1-10Alkyl or C_2-6An alkenyl group;

a group represented by the formula (II-3),

{ wherein, B represents

C_3-10A cycloalkyl group;

an aryl group;

a heterocyclic group;

C_2-6a cyclic amino group;

a group represented by the formula (III);

(wherein n represents 0 or 1)

Or a group represented by the formula (IV-3),

(in the formula, Y³represents-O-CH₂-CH ═ CH-or-O- (CH)₂) q-O-, q represents an integer of 1 to 3)

R⁵⁵³To represent

A hydrogen atom;

a halogen atom;

an aryl group;

C_1-10an alkyl group;

C_1-6alkanoyloxy group C_1-6An alkyl group;

C_1-6a haloalkyl group;

C_1-10an alkoxy group;

C_1-6an alkylthio group;

C_2-6an alkenyloxy group;

C_2-6an alkenylthio group;

C_1-6a haloalkoxy group;

C_1-6a haloalkylthio group;

aryl which may be substituted with 1 to 3 halogen atoms or cyano;

a heterocyclic group;

may be substituted by halogen atoms or C_1-6An alkyl-substituted aryloxy or arylthio group;

formula-N (R)⁶³³)R⁷³³(in the formula, R⁶³³And R⁷³³Each represents a hydrogen atom,C_1-6Alkyl radical, C_1-6Alkanoyl, di-C_1-6Alkylamino radical C_2-6Alkanoyl or may be substituted by C_1-6An alkyl-substituted heterocyclic group, or a group which represents a cyclic amino group bonded together with an adjacent nitrogen atom);

a cyano group;

a nitro group;

C_2-6an alkoxycarbonyl group;

R⁵⁶³to represent

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group; or

C_1-6A halogenated alkyl group,

R⁵⁷³to represent

A hydrogen atom;

C_1-10an alkyl group;

a halogen atom; or

C_1-10An alkoxy group,

m represents an integer of 1 to 3, W represents-CO-, -CO-NH-, -CS-NH-or-SO₂-。]

49. The imine compound of claim 48, or a pharmaceutically acceptable salt thereof, R¹³Is a hydrogen atom or a phenyl group, R²³And R³³Are respectively C_1-6Alkyl radical, C_1-6Haloalkyl or C_3-10A cycloalkyl group,

R⁴³is composed of

Can be selected from C_3-10Cycloalkyl and C_1-6C substituted by radicals of alkoxy_1-10An alkyl group; or

C_1-6A halogenated alkyl group,

R⁵³is composed of

C_1-6An alkoxy group;

C_1-6alkoxy radical C_1-6An alkoxy group;

C_1-6a haloalkyl group;

can be selected from C_1-6Alkoxy radical, C_3-10Cycloalkyl radical, C_2-6Alkoxycarbonyl, can be selected from "C_1-6Aryl or aryloxy group substituted with 1 to 5 groups of alkoxy group and halogen atom ", heterocyclic group, C_1-6Alkanoyloxy, aralkyloxy and C_1-6C substituted by 1-3 groups in alkylthio group_1-10Alkyl or C_2-6An alkenyl group; or

A group represented by the formula (II-3),

b is aryl, furyl, thienyl, pyrazolyl, isoxazolyl, pyridyl, a group represented by the formula (III) or a group represented by the formula (IV-3).

50. The imine compound of claim 49, or a pharmaceutically acceptable salt thereof, wherein W is-CO-.

51. The imine compound according to claim 50 or a pharmaceutically acceptable salt thereof,

X³is C (R)¹³)，

R⁵³Is composed of

C_1-10An alkoxy group;

C_1-6a haloalkyl group;

can be selected from C_1-6Alkoxy radical, C_3-10Cycloalkyl and may be selected from "C_1-6Alkoxy and halogen atom' 1-5 groups substituted aryl group 1-3 groups substituted C_1-10An alkyl group; or

A group represented by the formula (II-3), B is a phenyl group.

52. The imine compound according to claim 51 or a pharmaceutically acceptable salt thereof,

R⁵⁵³is composed of

A halogen atom;

C_1-10an alkyl group;

C_1-6a haloalkyl group;

C_1-10an alkoxy group;

C_1-6a haloalkoxy group;

aryl which may be substituted with 1 to 3 halogen atoms;

aryloxy which may be substituted with halogen atom;

formula-N (R)⁶³³)R⁷³³(in the formula, R⁶³³And R⁷³³Each represents a hydrogen atom or C_1-6Alkyl) group;

a cyano group;

a nitro group; or

C_2-6An alkoxycarbonyl group, a carbonyl group,

R⁵⁶³is composed of

A hydrogen atom;

a halogen atom;

C_1-10an alkyl group; or

C_1-6A halogenated alkyl group,

R⁵⁷³is composed of

A hydrogen atom;

C_1-10an alkyl group;

a halogen atom; or

C_1-10An alkoxy group.

53. The imine compound of claim 52, or a pharmaceutically acceptable salt thereof, R⁴³Is C_3-10Cycloalkyl-substituted C_1-10An alkyl group.

54. The imine compound of claim 49, or a pharmaceutically acceptable salt thereof, X³Is a sulfur atom, W is-CO-or-SO₂-。

55. The imine compound of claim 54, or a pharmaceutically acceptable salt thereof, R²³Is C_1-6Alkyl radical, R⁴³Is C_3-10Cycloalkyl-substituted C_1-10Alkyl radical, R⁵³Is a group represented by the formula (II-3), B is an aryl group, R⁵⁵³Is C_1-6Haloalkyl, R⁵⁶³Is a hydrogen atom, a halogen atom, C_1-10Alkyl or C_1-10Alkoxy radical, R⁵⁷³Is a hydrogen atom.

56. The imine compound according to any one of claims 50 to 55, wherein the steric configuration of the double bond of the group represented by > C ═ N-CO-in formula (I-3) is in the (Z) configuration, or a pharmaceutically acceptable salt thereof.