SK285878B6 - Derivát 2-kyaniminoimidazolu, prostriedok obsahujúci tento derivát, spôsob prípravy tohto prostriedku, uvedený derivát na použitie ako liečivo, použitie tohto derivátu na prípravu liečiva a spôsob prípravy tohto derivátu - Google Patents

Derivát 2-kyaniminoimidazolu, prostriedok obsahujúci tento derivát, spôsob prípravy tohto prostriedku, uvedený derivát na použitie ako liečivo, použitie tohto derivátu na prípravu liečiva a spôsob prípravy tohto derivátu Download PDF

Info

Publication number: SK285878B6
Authority: SK; Slovakia
Prior art keywords: alkyl; group; substituted; formula; hydrogen
Prior art date: 1996-10-02

Application number

SK344-99A

Other languages

English (en)

Slovak (sk)

Other versions

SK34499A3 (en

Inventor

Eddy Jean Edgard Freyne

Francisco Javier Fernandez-Gadea

Jos� Ignacio Andr�S-Gil

Original Assignee

Janssen Pharmaceutica N. V.

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1996-10-02

Filing date

1997-09-24

Publication date

2007-10-04

1997-09-24 Application filed by Janssen Pharmaceutica N. V. filed Critical Janssen Pharmaceutica N. V.

2000-04-10 Publication of SK34499A3 publication Critical patent/SK34499A3/sk

2007-10-04 Publication of SK285878B6 publication Critical patent/SK285878B6/sk

Links

UCPBYQVLXUIDCK-UHFFFAOYSA-N imidazol-2-ylidenecyanamide Chemical class N#CN=C1N=CC=N1 UCPBYQVLXUIDCK-UHFFFAOYSA-N 0.000 title claims abstract description 15
230000002401 inhibitory effect Effects 0.000 title abstract description 13
150000001875 compounds Chemical class 0.000 claims abstract description 90
-1 6,7-dihydro-5H- cyclopentapyridinyl Chemical group 0.000 claims abstract description 88
239000001257 hydrogen Substances 0.000 claims abstract description 41
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 41
150000003839 salts Chemical class 0.000 claims abstract description 27
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 25
125000003118 aryl group Chemical group 0.000 claims abstract description 21
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 20
150000002431 hydrogen Chemical group 0.000 claims abstract description 18
238000000034 method Methods 0.000 claims abstract description 17
125000003386 piperidinyl group Chemical group 0.000 claims abstract description 16
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 13
125000005843 halogen group Chemical group 0.000 claims abstract description 13
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims abstract description 13
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 11
125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims abstract description 10
125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims abstract description 10
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 10
125000004391 aryl sulfonyl group Chemical group 0.000 claims abstract description 8
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 8
125000000008 (C1-C10) alkyl group Chemical group 0.000 claims abstract description 5
125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims abstract description 3
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 3
125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract 4
239000000203 mixture Substances 0.000 claims description 59
125000004432 carbon atom Chemical group C* 0.000 claims description 24
239000002253 acid Substances 0.000 claims description 22
238000006243 chemical reaction Methods 0.000 claims description 19
125000000217 alkyl group Chemical group 0.000 claims description 18
239000002585 base Substances 0.000 claims description 17
125000004193 piperazinyl group Chemical group 0.000 claims description 14
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
125000002541 furyl group Chemical group 0.000 claims description 12
238000002360 preparation method Methods 0.000 claims description 12
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
125000004076 pyridyl group Chemical group 0.000 claims description 12
125000001544 thienyl group Chemical group 0.000 claims description 12
239000004480 active ingredient Substances 0.000 claims description 10
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 10
125000002757 morpholinyl group Chemical group 0.000 claims description 10
125000001424 substituent group Chemical group 0.000 claims description 10
XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 claims description 9
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 9
239000012442 inert solvent Substances 0.000 claims description 9
125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 9
125000000753 cycloalkyl group Chemical group 0.000 claims description 7
125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 7
239000003814 drug Substances 0.000 claims description 7
239000003937 drug carrier Substances 0.000 claims description 7
125000005879 dioxolanyl group Chemical group 0.000 claims description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 6
125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 6
125000003342 alkenyl group Chemical group 0.000 claims description 5
208000006673 asthma Diseases 0.000 claims description 5
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 5
125000003830 C1- C4 alkylcarbonylamino group Chemical group 0.000 claims description 4
SLIKWVTWIGHFJE-UHFFFAOYSA-N diphenoxymethylidenecyanamide Chemical compound C=1C=CC=CC=1OC(=NC#N)OC1=CC=CC=C1 SLIKWVTWIGHFJE-UHFFFAOYSA-N 0.000 claims description 4
125000002883 imidazolyl group Chemical group 0.000 claims description 4
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
125000002971 oxazolyl group Chemical group 0.000 claims description 4
125000000335 thiazolyl group Chemical group 0.000 claims description 4
150000001204 N-oxides Chemical class 0.000 claims description 3
229910021645 metal ion Inorganic materials 0.000 claims description 3
231100000252 nontoxic Toxicity 0.000 claims description 3
230000003000 nontoxic effect Effects 0.000 claims description 3
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 2
206010003645 Atopy Diseases 0.000 claims description 2
125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 2
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 2
125000005167 cycloalkylaminocarbonyl group Chemical group 0.000 claims description 2
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
239000012458 free base Substances 0.000 claims description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
125000002524 organometallic group Chemical group 0.000 claims description 2
YZXKVXNKAJKWBK-UHFFFAOYSA-N 1H-imidazol-2-ylcyanamide Chemical class C(#N)NC=1NC=CN=1 YZXKVXNKAJKWBK-UHFFFAOYSA-N 0.000 claims 1
239000003513 alkali Substances 0.000 claims 1
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims 1
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract description 20
229920006395 saturated elastomer Polymers 0.000 abstract description 15
102000004127 Cytokines Human genes 0.000 abstract description 14
108090000695 Cytokines Proteins 0.000 abstract description 14
229910052757 nitrogen Chemical group 0.000 abstract description 12
125000000623 heterocyclic group Chemical group 0.000 abstract description 9
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract description 7
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract description 7
125000005842 heteroatom Chemical group 0.000 abstract description 7
229910052760 oxygen Inorganic materials 0.000 abstract description 7
239000001301 oxygen Substances 0.000 abstract description 7
239000008194 pharmaceutical composition Substances 0.000 abstract description 7
229910052717 sulfur Inorganic materials 0.000 abstract description 7
239000011593 sulfur Chemical group 0.000 abstract description 7
125000000815 N-oxide group Chemical group 0.000 abstract description 6
BVCRERJDOOBZOH-UHFFFAOYSA-N bicyclo[2.2.1]heptanyl Chemical group C1C[C+]2CC[C-]1C2 BVCRERJDOOBZOH-UHFFFAOYSA-N 0.000 abstract 1
239000000543 intermediate Substances 0.000 description 55
239000002904 solvent Substances 0.000 description 50
239000000243 solution Substances 0.000 description 26
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 24
108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 24
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 20
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
239000011541 reaction mixture Substances 0.000 description 18
239000003480 eluent Substances 0.000 description 17
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 17
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
230000000694 effects Effects 0.000 description 14
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 12
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
239000012044 organic layer Substances 0.000 description 12
108010037444 diisopropylglutathione ester Proteins 0.000 description 11
210000004027 cell Anatomy 0.000 description 10
201000010099 disease Diseases 0.000 description 10
230000005764 inhibitory process Effects 0.000 description 10
208000012657 Atopic disease Diseases 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
208000026935 allergic disease Diseases 0.000 description 9
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
238000010898 silica gel chromatography Methods 0.000 description 8
239000003826 tablet Substances 0.000 description 8
239000007983 Tris buffer Substances 0.000 description 7
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LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 7
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HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
229910052799 carbon Inorganic materials 0.000 description 6
238000004811 liquid chromatography Methods 0.000 description 6
239000011734 sodium Substances 0.000 description 6
229920000858 Cyclodextrin Polymers 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
238000004587 chromatography analysis Methods 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
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229910002027 silica gel Inorganic materials 0.000 description 5
239000000725 suspension Substances 0.000 description 5
239000007868 Raney catalyst Substances 0.000 description 4
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 4
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CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
150000001412 amines Chemical class 0.000 description 4
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/44—Nitrogen atoms not forming part of a nitro radical
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/44—Nitrogen atoms not forming part of a nitro radical
- C07D233/48—Nitrogen atoms not forming part of a nitro radical with acyclic hydrocarbon or substituted acyclic hydrocarbon radicals, attached to said nitrogen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/88—Nitrogen atoms, e.g. allantoin

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Pulmonology (AREA)
Immunology (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Dermatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

SK344-99A 1996-10-02 1997-09-24 Derivát 2-kyaniminoimidazolu, prostriedok obsahujúci tento derivát, spôsob prípravy tohto prostriedku, uvedený derivát na použitie ako liečivo, použitie tohto derivátu na prípravu liečiva a spôsob prípravy tohto derivátu SK285878B6 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP96202749		1996-10-02
PCT/EP1997/005322 WO1998014432A1 (en)	1996-10-02	1997-09-24	Pde iv inhibiting 2-cyanoiminoimidazole derivatives

Publications (2)

Publication Number	Publication Date
SK34499A3 SK34499A3 (en)	2000-04-10
SK285878B6 true SK285878B6 (sk)	2007-10-04

Family

ID=8224456

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK344-99A SK285878B6 (sk)	1996-10-02	1997-09-24	Derivát 2-kyaniminoimidazolu, prostriedok obsahujúci tento derivát, spôsob prípravy tohto prostriedku, uvedený derivát na použitie ako liečivo, použitie tohto derivátu na prípravu liečiva a spôsob prípravy tohto derivátu

Country Status (30)

Country	Link
US (1)	US6051718A (es)
EP (1)	EP0934280B1 (es)
JP (1)	JP3068208B2 (es)
KR (1)	KR100520002B1 (es)
CN (1)	CN1106387C (es)
AR (1)	AR008875A1 (es)
AT (1)	ATE236884T1 (es)
AU (1)	AU719561B2 (es)
BG (1)	BG64278B1 (es)
BR (1)	BR9712256B1 (es)
CA (1)	CA2267322C (es)
CY (1)	CY2380B1 (es)
CZ (1)	CZ297474B6 (es)
DE (1)	DE69720757T2 (es)
DK (1)	DK0934280T3 (es)
EE (1)	EE03825B1 (es)
ES (1)	ES2196308T3 (es)
HU (1)	HU225158B1 (es)
IL (2)	IL129298A0 (es)
MY (1)	MY116980A (es)
NO (1)	NO312960B1 (es)
NZ (1)	NZ334971A (es)
PL (1)	PL194673B1 (es)
PT (1)	PT934280E (es)
RU (1)	RU2180902C2 (es)
SI (1)	SI0934280T1 (es)
SK (1)	SK285878B6 (es)
TR (1)	TR199900732T2 (es)
UA (1)	UA62939C2 (es)
WO (1)	WO1998014432A1 (es)

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US6953774B2 (en)	2000-08-11	2005-10-11	Applied Research Systems Ars Holding N.V.	Methods of inducing ovulation
WO2002085855A1 (fr)	2001-04-19	2002-10-31	Eisai Co., Ltd.	Derives de 2-iminopyrrolidine
US20040180900A1 (en)	2001-05-23	2004-09-16	Masaharu Takigawa	Therapeutic composition for repairing chondropathy
CN100358514C (zh) *	2001-07-11	2008-01-02	日研化学株式会社	过敏性眼疾病治疗剂
TWI221838B (en)	2001-08-09	2004-10-11	Tanabe Seiyaku Co	Pyrazinoisoquinoline compound or naphthalene compound
WO2003051344A1 (en)	2001-12-14	2003-06-26	Applied Research Systems Ars Holding N.V.	Methods of inducing ovulation_using a non-polypeptide camp level modulator
WO2004078721A1 (ja)	2003-02-19	2004-09-16	Eisai Co., Ltd.	環状ベンズアミジン誘導体の製造方法
EP2258359A3 (en)	2005-08-26	2011-04-06	Braincells, Inc.	Neurogenesis by muscarinic receptor modulation with sabcomelin
EP1928437A2 (en)	2005-08-26	2008-06-11	Braincells, Inc.	Neurogenesis by muscarinic receptor modulation
JP2009512711A (ja)	2005-10-21	2009-03-26	ブレインセルス，インコーポレイティド	Ｐｄｅ阻害による神経新生の調節
WO2007053596A1 (en)	2005-10-31	2007-05-10	Braincells, Inc.	Gaba receptor mediated modulation of neurogenesis
US20100216734A1 (en)	2006-03-08	2010-08-26	Braincells, Inc.	Modulation of neurogenesis by nootropic agents
WO2007134136A2 (en)	2006-05-09	2007-11-22	Braincells, Inc.	Neurogenesis by modulating angiotensin
US20100184806A1 (en)	2006-09-19	2010-07-22	Braincells, Inc.	Modulation of neurogenesis by ppar agents
WO2010099217A1 (en)	2009-02-25	2010-09-02	Braincells, Inc.	Modulation of neurogenesis using d-cycloserine combinations
EP2804603A1 (en)	2012-01-10	2014-11-26	President and Fellows of Harvard College	Beta-cell replication promoting compounds and methods of their use
WO2013184755A2 (en) *	2012-06-07	2013-12-12	Georgia State University Research Foundation, Inc.	Seca inhibitors and methods of making and using thereof
GB2533925A (en) *	2014-12-31	2016-07-13	Univ Bath	Antimicrobial compounds, compositions and methods
CN109438434B (zh) *	2018-11-19	2021-05-04	华南农业大学	一种含噁唑环的2-氰基亚氨基噻唑烷类化合物及其制备方法和应用

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JPH05310650A (ja) *	1991-08-22	1993-11-22	Nippon Soda Co Ltd	新規なアミン誘導体、その製造方法及び殺虫剤
JP3775684B2 (ja) *	1992-07-28	2006-05-17	ローン−プーラン・ロレ・リミテツド	脂肪族−またはヘテロ原子−含有連結基によりアリールまたはヘテロアリールに連結されたフェニル含有化合物
AU673569B2 (en) *	1992-12-02	1996-11-14	Pfizer Inc.	Catechol diethers as selective PDE-IV inhibitors
GB9304919D0 (en) *	1993-03-10	1993-04-28	Celltech Ltd	Chemical compounds
DE69430747T2 (de) *	1993-07-28	2003-03-06	Aventis Pharma Ltd., West Malling	Verbindungen als pde iv und tnf inhibitoren
EP0714397A1 (en) *	1993-08-19	1996-06-05	Smithkline Beecham Corporation	Phenethylamine compounds
GB9401460D0 (en) *	1994-01-26	1994-03-23	Rhone Poulenc Rorer Ltd	Compositions of matter
ATE217865T1 (de) *	1994-06-24	2002-06-15	Euro Celtique Sa	Verbindungen zur hemmung von phosphodiesrerase iv
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TW375612B (en) *	1995-04-06	1999-12-01	Janssen Pharmaceutica Nv	1,3-dihydro-2H-imidazol-2-one derivatives for the treatment of disease states related to an abnormal enzymatic or catalytic activity of phosphodiesterase type IV, preparation thereof and pharmaceutical composition containing the same
TW332201B (en) *	1995-04-06	1998-05-21	Janssen Pharmaceutica Nv	1,3-Dihydro-1-(phenylalkyl)-2H-imidazol-2-one derivatives

1997
- 1997-09-24 WO PCT/EP1997/005322 patent/WO1998014432A1/en not_active Ceased
- 1997-09-24 CN CN97198460A patent/CN1106387C/zh not_active Expired - Lifetime
- 1997-09-24 TR TR1999/00732T patent/TR199900732T2/xx unknown
- 1997-09-24 RU RU99109032/04A patent/RU2180902C2/ru active
- 1997-09-24 PL PL97332573A patent/PL194673B1/pl unknown
- 1997-09-24 JP JP10516215A patent/JP3068208B2/ja not_active Expired - Lifetime
- 1997-09-24 AT AT97910380T patent/ATE236884T1/de active
- 1997-09-24 PT PT97910380T patent/PT934280E/pt unknown
- 1997-09-24 UA UA99031702A patent/UA62939C2/uk unknown
- 1997-09-24 IL IL12929897A patent/IL129298A0/xx active IP Right Grant
- 1997-09-24 US US09/147,925 patent/US6051718A/en not_active Expired - Lifetime
- 1997-09-24 EE EEP199900112A patent/EE03825B1/xx unknown
- 1997-09-24 SI SI9730550T patent/SI0934280T1/xx unknown
- 1997-09-24 HU HU9904063A patent/HU225158B1/hu unknown
- 1997-09-24 EP EP97910380A patent/EP0934280B1/en not_active Expired - Lifetime
- 1997-09-24 AU AU47792/97A patent/AU719561B2/en not_active Expired
- 1997-09-24 ES ES97910380T patent/ES2196308T3/es not_active Expired - Lifetime
- 1997-09-24 KR KR10-1999-7001204A patent/KR100520002B1/ko not_active Expired - Lifetime
- 1997-09-24 DK DK97910380T patent/DK0934280T3/da active
- 1997-09-24 CA CA002267322A patent/CA2267322C/en not_active Expired - Lifetime
- 1997-09-24 CZ CZ0102899A patent/CZ297474B6/cs not_active IP Right Cessation
- 1997-09-24 NZ NZ334971A patent/NZ334971A/xx not_active IP Right Cessation
- 1997-09-24 SK SK344-99A patent/SK285878B6/sk not_active IP Right Cessation
- 1997-09-24 BR BRPI9712256-4A patent/BR9712256B1/pt not_active IP Right Cessation
- 1997-09-24 DE DE69720757T patent/DE69720757T2/de not_active Expired - Lifetime
- 1997-10-01 AR ARP970104528A patent/AR008875A1/es active IP Right Grant
- 1997-10-02 MY MYPI97004600A patent/MY116980A/en unknown
1999
- 1999-03-01 BG BG103220A patent/BG64278B1/bg unknown
- 1999-03-30 NO NO19991560A patent/NO312960B1/no not_active IP Right Cessation
- 1999-03-31 IL IL129298A patent/IL129298A/en not_active IP Right Cessation
2003
- 2003-11-04 CY CY0300074A patent/CY2380B1/xx unknown

Also Published As

Publication number	Publication date
BR9712256B1 (pt)	2011-04-19
HUP9904063A3 (en)	2000-11-28
DE69720757T2 (de)	2004-03-04
CA2267322C (en)	2007-11-06
BG64278B1 (bg)	2004-08-31
CN1232456A (zh)	1999-10-20
SI0934280T1 (en)	2003-12-31
NZ334971A (en)	2000-09-29
CY2380B1 (en)	2004-06-04
DE69720757D1 (de)	2003-05-15
EP0934280A1 (en)	1999-08-11
PL194673B1 (pl)	2007-06-29
PL332573A1 (en)	1999-09-27
ES2196308T3 (es)	2003-12-16
NO991560D0 (no)	1999-03-30
HU225158B1 (en)	2006-07-28
CA2267322A1 (en)	1998-04-09
RU2180902C2 (ru)	2002-03-27
JP3068208B2 (ja)	2000-07-24
KR100520002B1 (ko)	2005-10-13
EE9900112A (et)	1999-10-15
NO991560L (no)	1999-06-02
UA62939C2 (uk)	2004-01-15
NO312960B1 (no)	2002-07-22
ATE236884T1 (de)	2003-04-15
EE03825B1 (et)	2002-08-15
AU719561B2 (en)	2000-05-11
HK1020344A1 (en)	2000-04-14
AU4779297A (en)	1998-04-24
WO1998014432A1 (en)	1998-04-09
AR008875A1 (es)	2000-02-23
KR20000029964A (ko)	2000-05-25
TR199900732T2 (xx)	1999-08-23
IL129298A0 (en)	2000-02-17
US6051718A (en)	2000-04-18
SK34499A3 (en)	2000-04-10
BG103220A (en)	1999-11-30
IL129298A (en)	2006-04-10
HUP9904063A2 (hu)	2000-09-28
MY116980A (en)	2004-04-30
JP2000503678A (ja)	2000-03-28
BR9712256A (pt)	1999-08-24
PT934280E (pt)	2003-08-29
DK0934280T3 (da)	2003-07-21
CZ297474B6 (cs)	2006-12-13
CN1106387C (zh)	2003-04-23
CZ102899A3 (cs)	1999-07-14
EP0934280B1 (en)	2003-04-09

Publication	Publication Date	Title
SK285878B6 (sk)	2007-10-04	Derivát 2-kyaniminoimidazolu, prostriedok obsahujúci tento derivát, spôsob prípravy tohto prostriedku, uvedený derivát na použitie ako liečivo, použitie tohto derivátu na prípravu liečiva a spôsob prípravy tohto derivátu
US5994376A (en)	1999-11-30	1,3-dihydro-1-(phenylalkyl)-2H-imidazol-2-one compounds and their use for treating allergic, atopic or inflammatory diseases
EP0819123B1 (en)	2007-12-12	1,3-dihydro-1-(phenylalkenyl)-2h-imidazol-2-one derivatives having pde iv and cytokine inhibiting activity
KR100400159B1 (ko)	2003-12-31	Pdeiv및사이토킨억제활성을가진1,3-디하이드로-2h-이미다졸-2-온유도체
US6656959B1 (en)	2003-12-02	PDE IV inhibiting pyridine derivatives
HK1020344B (en)	2003-07-25	Pde iv inhibiting 2-cyanoiminoimidazole derivatives
MXPA00009632A (es)	2001-07-31	Derivados de piridina inhibidores de las fosfodiesterasa iv
HK1033579B (en)	2004-02-27	Pde iv inhibiting pyridine derivatives

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2017-11-03	MK4A	Expiry of patent	Expiry date: 20170924