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WO1995018127A1 - Aza-4-iminoquinoleines, leur procede de production et leur utilisation - Google Patents

Aza-4-iminoquinoleines, leur procede de production et leur utilisation Download PDF

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Publication number
WO1995018127A1
WO1995018127A1 PCT/EP1994/003976 EP9403976W WO9518127A1 WO 1995018127 A1 WO1995018127 A1 WO 1995018127A1 EP 9403976 W EP9403976 W EP 9403976W WO 9518127 A1 WO9518127 A1 WO 9518127A1
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Prior art keywords
chlorine
fluorine
alkoxy
optionally substituted
hydroxy
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PCT/EP1994/003976
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German (de)
English (en)
Inventor
Reinhard Kirsch
Manfred Rösner
Rudolf Bender
Christoph Meichsner
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Hoechst AG
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Hoechst AG
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Priority to AU11086/95A priority Critical patent/AU1108695A/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

Definitions

  • the present invention relates to aza-4-aminoquinolines, processes for their preparation and their use.
  • the individual substituents R 1 are, independently of one another, fluorine, chlorine, bromine, iodine, trifluoromethyl, trifluoromethoxy, hydroxyl, mercapto, alkyl, cycloalkyl, alkoxy, alkoxyalkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, where the alkyl groups can be substituted by fluorine, Chlorine, hydroxy, amino, alkoxy, alkylamino, dialkylamino, acyloxy, acylamino, carboxy, aminocarbonyl, alkyloxycarbonyl;
  • R 5 phenyl, phenoxy, phenoxycarbonyl, phenylthio, phenylsulfinyl, phenylsulfonyl, phenoxysulfonyl, phenylsulfonyloxy, anilinosulfonyl, phenylsulfonylamino, benzoyl, or heteroaryl where R 5
  • T, U, V and W represent CH, CR 1 or N, with a minimum of one and a maximum of two nitrogen atoms in the ring,
  • X represents oxygen, sulfur, selenium or substituted nitrogen NR 2 , where R 2 can have the meanings given below,
  • R 2 , R 6 , R 7 and R 8 can be the same or different, independently of one another hydrogen
  • Alkyl optionally substituted with fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
  • Alkenyl optionally substituted with fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl; Alkynyl, optionally substituted with fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
  • Cycloalkyl optionally substituted with fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
  • Cycloalkenyl optionally substituted with fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
  • Alkylcarbonyl optionally substituted with fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
  • Alkenylcarbonyl optionally substituted by fluorine, chlorine or hydroxy, alkoxy, oxo, phenyl
  • (Cycloalkyl) carbonyl optionally substituted by fluorine, chlorine or hydroxy, alkoxy, oxo, phenyl
  • Alkyloxycarbonyl optionally substituted by fluorine, chlorine, bromine, hydroxy, alkoxy, alkylamino, dialkylamino, alkylthio;
  • Alkenyloxycarbonyl optionally substituted by fluorine, chlorine, hydroxy, alkoxy, oxo, phenyl;
  • Alkynyloxycarbonyl optionally substituted by fluorine, chlorine, hydroxy, alkoxy, oxo, phenyl;
  • Alkylthiocarbonyl optionally substituted by fluorine, chlorine, hydroxy, alkoxy, oxo, phenyl;
  • Alkenylthiocarbonyl optionally substituted by fluorine, chlorine, hydroxy, alkoxy, oxo, phenyl;
  • Alkylamino and dialkylaminocarbonyl optionally substituted by fluorine, chlorine, hydroxy, alkoxy, oxo, phenyl;
  • Alkenylamino- and dialkenylaminocarbonyl optionally substituted by fluorine, chlorine, hydroxy, alkoxy, oxo, phenyl
  • Alkylsulfonyl optionally substituted by fluorine, chlorine, hydroxy, alkoxy, alkylthio, oxo, phenyl
  • Alkenylsulfonyl optionally substituted by fluorine, chlorine, hydroxy, alkoxy, oxo, phenyl;
  • arylcarbonyl aryl (thiocarbonyl), (arylthio) carbonyl, (arylthio) thiocarbonyl, aryloxycarbonyl, (arylamino) thiocarbonyl, arylsulfonyl, arylalkyl, arylalkenyl, arylalkynyl, arylalkylcarbonylcarbonyl, substituted with up to five mutually independent radicals R 5 where R 5 is as defined above or heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkylcarbonyl or heteroarylalkenylcarbonyl substituted with up to three mutually independent radicals R 5 ,
  • R 3 and R 4 denote the same or different, independently of one another, hydrogen
  • Alkyl optionally substituted with fluorine, chlorine, hydroxy, amino, mercapto, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, alkylsulfinyl, carboxy, carbamoyl,
  • Alkenyl optionally substituted with fluorine or chlorine, hydroxy, amino, mercapto, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, alkylsulfinyl, carboxy, carbamoyl,
  • Cycloalkyl optionally substituted with fluorine, chlorine, hydroxy, amino, mercapto, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, alkylsulfinyl, carboxy, carbamoyl, Cycloalkenyl, optionally substituted with fluorine or chlorine, hydroxy, amino, mercapto, acyloxy, benzoyloxy, benzyloxy, phenoxy, alkoxy, alkylamino, dialkylamino, alkylthio, alkylsulfonyl, alkylsulfinyl, carboxy, carbamoyl;
  • aryl, arylalkyl, heteroaryl or heteroarylalkyl substituted with up to five mutually independent radicals R 5 , where R 5 is as defined above,
  • R 3 and R 4 or R 3 and Y can also be part of a saturated or unsaturated carbocyclic or heterocyclic ring which may optionally be substituted with fluorine, chlorine, hydroxy, amino, alkyl, alkenyl, alkynyl, acyloxy, benzoyloxy, alkoxy, alkylthio, Oxo, thioxo, carboxy, carbamoyl or phenyl can be substituted.
  • Suitable heteroatoms are, in particular, O, S, N, NZ being present in the case of an N-containing ring saturated at this point, where Z is H or R 2 .
  • T, U, V and W represent CH, CR 1 or N, with a minimum of one and a maximum of two nitrogen atoms in the ring,
  • X represents oxygen, sulfur, selenium or substituted nitrogen NR 2 , where R 2 can have the meanings given below,
  • R 2 , R 6 , R 7 and R 8 can be the same or different, independently of one another hydrogen, C r C 8 alkyl, optionally substituted with fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, C r C 6 acyloxy, benzoyloxy, benzyloxy, phenoxy, CC 6 alkoxy, C r C 6 alkylamino , Di (CC 6 alkyl) amino, C 1 -C 6 alkylthio, C r C 6 alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
  • C 2 -C 8 alkenyl optionally substituted with fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, C 1 -C 6 acyloxy, benzoyloxy, benzyloxy, phenoxy, C 1 -C 6 alkoxy, CC 6 -alkylamino, di (C 1 -C 6 -alkyl) amino, C 1 -C 6 -alkylthio, C, - C 6 -alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
  • C 3 -C 8 alkynyl optionally substituted with fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, C r C 6 acyloxy, benzoyloxy, benzyloxy, phenoxy, C Cg alkoxy, C ** - C 6- alkylamino, di (C, -C 6 -alkyl) amino, C * -Cg-alkylthio, C r Cg-alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
  • C 3 -C 8 cycloalkyl optionally substituted with fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, C. * - C 6 -acyloxy, benzoyloxy, benzyloxy, phenoxy, C r C 6 alkoxy, C *, - C 6 alkylamino, di (C. * - Cg-alkyl) a ⁇ .ino, C - C 6 - alkylthio, C. * - C 6 alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
  • C 5 -C 8 cycloalkenyl optionally substituted with fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, C- j -Cg-acyloxy, benzoyloxy, benzyloxy, phenoxy, CC 6 -alkoxy, C ⁇ Cg- Alkylamino, DKC ⁇ C -alkyDamino, C, -C 6 -alkylthio, C ⁇ Cg-alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
  • C j -Cg alkylcarbonyl optionally substituted with fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, C. * - C 6 acyloxy, benzoyloxy, benzyloxy, phenoxy, C r C 6 alkoxy, Ci Cg-alkylamino, di (C *
  • (C 3 -C 8 cycloalkyl) carbonyl optionally substituted by fluorine, chlorine or hydroxy, C r C 4 alkoxy, oxo, phenyl;
  • (C 5 -C 8 cycloalkenyl) carbonyl optionally substituted by fluorine, chlorine or hydroxy, C 1 -C 4 alkoxy, oxo, phenyl;
  • C 1 -C 6 -alkyloxycarbonyl optionally substituted by fluorine, chlorine, bromine, hydroxyl, C 2 -C 4 -alkoxy, C 2 -C 4 -alkylamino, di (C 1 -C 4 -alkyl) amino, CC 4 - alkylthio; C 2 -C 8 alkenyloxycarbonyl, optionally substituted by fluorine, chlorine, hydroxy, C r C 4 alkoxy, oxo, phenyl;
  • arylcarbonyl aryl (thiocarbonyl), (arylthio) carbonyl, (arylthio) thiocarbonyl, aryloxycarbonyl, (arylamino) thiocarbonyl, arylsulfonyl, arylalkyl, arylalkenyl, arylalkynyl, arylalkylcarbonyl, carbonyl substituted with up to three mutually independent radicals R 5 , wherein the alkyl radical can contain 1 to 5 carbon atoms and R 5 is as defined above or heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkylcarbonyl or heteroarylalkenylcarbonyl substituted with up to three mutually independent radicals R 5 , where the alkyl radical can each contain 1 to 3 carbon atoms,
  • R 3 and R 4 denote the same or different, independently of one another, hydrogen
  • C * -C 8 alkyl optionally substituted with fluorine, chlorine, hydroxy, amino, mercapto, C, -C 4 acyloxy, benzoyloxy, benzyloxy, phenoxy, C, -C 4 alkoxy, C r C 4 alkylamino, Di (C r C 4 alkyl) amino, C r C 4 alkylthio, C r C 4 alkylsulfonyl, C * -C 4 alkylsulfinyl, carboxy, carbamoyl;
  • C 2 -C 8 alkenyl optionally substituted with fluorine or chlorine, hydroxy, amino, mercapto, C r C 4 - acyloxy, benzoyloxy, benzyloxy, phenoxy, C ** - C 4 - alkoxy, C r C 4 alkylamino, Di (CC 4 alkyl) amino, C r C 4 alkylthio, C r C 4 alkylsulfonyl, CC 4 alkylsulfinyl, carboxy, carbamoyl;
  • C 3 -C 8 cycloalkyl optionally substituted with fluorine, chlorine, hydroxy, amino, mercapto, C - * - C 4 acyloxy, benzoyloxy, benzyloxy, phenoxy, C 1 -C 4 alkoxy, C r C 4 alkylamino , Di (C r C 4 alkyl) amino, C r C 4 alkylthio, C r C 4 alkylsulfonyl, C. * - C 4 alkylsulfinyl, carboxy, carbamoyl;
  • C 3 -C 8 cycloalkenyl optionally substituted with fluorine or chlorine, hydroxy, amino, mercapto, C * -C 4 -acyloxy, benzoyloxy, benzyloxy, phenoxy, C, -C 4 -alkoxy, C r C 4 -alkylamino, Di (C r C 4 alkyl) amino, C r C 4 alkylthio, C r C 4 alkylsulfonyl, C ** - C 4 alkylsulfinyl, carboxy, carbamoyl;
  • aryl, arylalkyl, heteroaryl or heteroarylalkyl which are substituted by up to three mutually independent radicals R 5 , the alkyl radical in each case Can contain 1 to 3 carbon atoms and R 5 is as defined above,
  • R 3 and R 4 or R 3 and Y can also also also also also also also also also also also
  • Fluorine, chlorine, trifluoromethyl, C r C 4 alkyl, C * - C 4 may be alkoxy
  • T, U, V and W represent CH, CR 1 or N, with a minimum of one and a maximum of two nitrogen atoms in the ring,
  • X represents oxygen, sulfur or substituted nitrogen NR 2 , where R 2 can have the meanings given below.
  • R 2 , R 8 , R 7 and R 8 can be the same or different, independently of one another hydrogen
  • -C 6 alkyl optionally substituted with fluorine, chlorine, bromine, iodine, cyano, amino, mercapto, hydroxy, C ** - C 4 acyloxy, benzoyloxy, benzyloxy, phenoxy, C r C 4 alkoxy, C r C 4 -alkylamino, di (C r C 4 -alkyl) amino, C r C 4 -alkylthio, C r C 4 -alkylsulfonyl, phenylsulfonyl, oxo, thioxo, carboxy, carbamoyl;
  • C 2 -C 6 alkenyl optionally substituted with fluorine, chlorine, cyano, amino, mercapto, hydroxy, C ** - C 4 -acyloxy, benzoyloxy, benzyloxy, phenoxy, C r C 4 - alkoxy, C j -C ⁇ Alkylamino, di (C r C 4 alkyl) amino, C r C 4 alkylthio, C * -C 4 alkylsulfonyl, phenylsulfonyl, carboxy, carbamoyl;
  • C 3 -C 6 alkynyl optionally substituted with fluorine, chlorine, cyano, amino, mercapto, hydroxy, C r C 4 acyloxy, benzoyloxy, benzyloxy, phenoxy, C ** - C 4 - alkoxy, C r C 4 - Alkylamino, di (C 1 -C 4 alkyl) amino, C r C 4 alkylthio, CC 4 - alkylsulfonyl, phenylsulfonyl, carboxy, carbamoyl;
  • C 3 -C 6 cycloalkyl optionally substituted with fluorine, chlorine, cyano, amino, mercapto, hydroxy, C ** - C 4 -acyloxy, benzoyloxy, benzyloxy, phenoxy, C - C 4 - alkoxy, C r C 4 Alkylamino, di (C. * - C 4 alkyl) amino, C r C 4 alkylthio, C ** - C 4 alkylsulfonyl, phenylsulfonyl, carboxy, carbamoyl;
  • C 5 -C 6 cycloalkenyl optionally substituted with fluorine, chlorine, cyano, amino, mercapto, hydroxy, C. * - C 4 -acyloxy, benzoyloxy, benzyloxy, phenoxy, C * -C 4 - alkoxy, C r C 4 Alkylamino, di (C r C 4 alkyl) amino, C r C 4 alkylthio, C r C 4 alkylsulfonyl, phenylsulfonyl, carboxy, carbamoyl;
  • C- j -CG-alkylcarbonyl optionally substituted by fluorine, chlorine, cyano, amino, mercapto, hydroxy, C, -C 4 - acyloxy, benzoyloxy, benzyloxy, phenoxy, C r C 4 alkoxy, C r C 4 alkylamino , Di (CC 4 alkyl) amino, C r C 4 alkylthio, C r C 4 alkylsulfonyl, phenylsulfonyl, carboxy, carbamoyl;
  • arylcarbonyl aryl (thiocarbonyl), (arylthio) carbonyl, (arylthio) thiocarbonyl, aryloxycarbonyl, (arylamino) thiocarbonyl, arylsulfonyl, arylalkyl, arylalkenyl, arylalkynyl, arylalkylcarbonyl, carbonyl substituted with up to three mutually independent radicals R 5 , where the alkyl radical can contain 1 to 4 carbon atoms and R 5 is as defined above
  • heteroarylalkyl heteroarylalkenyl, heteroarylalkylcarbonyl or heteroarylalkenylcarbonyl substituted with up to three mutually independent radicals R 5 , where the alkyl radical can each contain 1 to 3 carbon atoms,
  • R 3 and R 4 mean the same or different, independently of one another
  • Cj-Cg-alkyl optionally substituted with fluorine, chlorine, hydroxy, amino, mercapto, C, -C 4 - acyloxy, benzoyloxy, benzyloxy, phenoxy, C * -C 4 alkoxy, C- j -C ⁇ alkylamino, Di (C r C 4 alkyl) amino, C r C 4 alkylthio, C, -C 4 alkylsulfonyl, C-
  • C 2 -C 6 alkenyl optionally substituted with fluorine or chlorine, phenoxy, C * -C 4 alkoxy, CC 4 alkylthio, C r C 4 alkylsulfonyl, C r C 4 alkylsulfinyl; C 3 -C 6 cycloalkyl, optionally substituted with fluorine, chlorine, hydroxy, amino, mercapto, C * -C 4 acyloxy, benzoyloxy, benzyloxy, phenoxy, C - C 4 alkoxy, CC 4 alkylamino, di ( C r C 4 alkyl) amino, C r C 4 alkylthio, C r C 4 alkylsulfonyl, C r C 4 alkylsulfinyl;
  • aryl, arylalkyl, heteroaryl or heteroarylalkyl substituted with up to three mutually independent radicals R5, where the alkyl radical can in each case contain 1 to 3 C atoms and R 5 is as defined above,
  • one of the radicals R 3 or R 4 can be hydrogen.
  • R 3 and R 4 or R 3 and Y can also also also also also also also also also also also
  • T, U, V and W represent CH, CR 1 or N, with a minimum of one and a maximum of two nitrogen atoms in the ring,
  • X represents oxygen, sulfur or substituted nitrogen NR 2 , where R 2 can have the meanings given below,
  • R 2 , R 6 , R 7 and R 8 mean the same or different, independently of one another
  • Ci-Cg-alkyl optionally substituted with fluorine, chlorine, amino, mercapto, hydroxy, C, -C 4 - acyloxy, benzoyloxy, benzyloxy, phenoxy, C
  • C 2 -C 6 alkenyl optionally substituted with fluorine, chlorine, amino, mercapto, hydroxy, C * -C 4 acyloxy, benzoyloxy, benzyloxy, phenoxy, C * -C 4 alkoxy, C- j -C ⁇ alkylamino , Di (. C, - C 4 alkyl) ar ⁇ .ino, C 1 -C 4 -alkylthio; C 3 -C 8 alkynyl, optionally substituted with fluorine, chlorine, amino, mercapto, hydroxy, C r C 4 -acyloxy, benzoyloxy, benzyloxy, phenoxy, C. * - C 4 -alkoxy, C., - C 4 - Alkylar ⁇ .ino, di (C. * - C 4 alkyl) amino, CC 4 alkylthio;
  • C 3 -C 6 cycloalkyl optionally substituted with fluorine, chlorine, C r C 4 acyloxy, benzoyloxy, phenoxy, C r C 4 alkoxy, C r C 4 alkylamino, C r C 4 alkylthio;
  • C 1 -C 4 -alkylcarbonyl optionally substituted with fluorine, chlorine, amino, mercapto, hydroxy, C 1 -C 4 -acyloxy, benzoyloxy, benzyloxy, phenoxy, CC 4 -alkoxy, C., - C 4 -alkylamino, di (C r C 4 alkyl) amino, C, -C 4 alkylthio;
  • arylcarbonyl aryl (thiocarbonyl), (arylthio) carbonyl, (arylthio) thiocarbonyl, aryloxycarbonyl, (arylamino) thiocarbonyl, arylsulfonyl, arylalkyl, arylalkenyl, arylalkynyl, arylalkylcarbonyl, carbonyl substituted with up to two mutually independent radicals R 5 , where the alkyl radical can each contain 1 to 3 carbon atoms and R 5 is as defined above under 3 or with up to two mutually independent radicals R 5 substituted heteroaryl, heteroarylalkyl, heteroarylalkenyl, heteroarylalkylcarbonyl or heteroarylalkenylcarbonyl, the alkyl radical in each case 1 to 2 Can contain carbon atoms,
  • R 3 and R 4 mean the same or different, independently of one another C- j -CG alkyl, optionally substituted by fluorine, chlorine, hydroxyl, amino, mercapto, C * -C 4 - acyloxy, benzoyloxy, benzyloxy, phenoxy, C ** - C 4 alkoxy, C r C 4 alkylamino , Di (C r C 4 alkyl) amino, C r C 4 alkylthio, C r C 4 alkylsulfonyl, C 1 -C 4 alkylsulfinyl, carboxy,
  • aryl, arylalkyl, heteroaryl or heteroarylalkyl which are substituted by up to three mutually independent radicals R 8 , where the alkyl radical can in each case contain 1 to 2 C atoms and R 5 is as defined above,
  • one of the radicals R 3 or R 4 can be hydrogen
  • R 3 and R 4 or R 3 and Y can also also also also also also also also also also also
  • Ib and Ic mean:
  • T, U, V and W represent CH or N, where a nitrogen atom is contained in the ring
  • X denotes oxygen, sulfur or substituted nitrogen N-R2, in which R2 can have the meanings given below,
  • R2, R6 and R7 mean the same or different, independently of one another
  • -C 6 alkyl optionally substituted with fluorine, chlorine, amino, mercapto, hydroxy, C * -C 4 acyloxy, benzoyloxy, benzyloxy, phenoxy, C r C 4 alkoxy, C r C 4 alkylamino, di (C r C 4 alkyl) amino, C r C 4 alkylthio;
  • C 2 -C 6 alkenyl optionally substituted with fluorine, chlorine, amino, mercapto, hydroxy, C * -C 4 acyloxy, benzoyloxy, benzyloxy, phenoxy, C r C 4 alkoxy, C r C 4 alkylamino, di (C r C 4 alkyl) amino, C r C 4 alkylthio;
  • C 3 -C 8 alkynyl optionally substituted with fluorine, chlorine, amino, mercapto, hydroxy, C - * - C 4 -acyloxy, benzoyloxy, benzyloxy, phenoxy, C 1 -C 4 -alkoxy, CC 4 -alkylamino, di (. C, - C 4 alkyl) amino, C, -C 4 alkylthio;
  • C 3 -C 6 cycloalkyl optionally substituted with fluorine, chlorine, C r C 4 acyloxy, benzoyloxy, phenoxy, C 1 -C 4 alkoxy, C 1 -C 4 alkylamino, di (C r C 4 alkyl) ) amino, C r C 4 alkylthio; C 5 -Cg cycloalkenyl,
  • arylcarbonyl aryl (thiocarbonyl), (arylthio) carbonyl, (arylthio) thiocarbonyl, aryloxycarbonyl, (arylamino) thiocarbonyl, arylsulfonyl, arylalkyl, arylalkenyl, arylalkynyl, arylalkylcarbonyl, carbonyl substituted with up to two mutually independent radicals R 5 , where the alkyl radical can contain 1 to 3 carbon atoms and R 5 is chlorine, trifluoromethyl, C. * - C 4 alkyl or C - * - C 4 alkoxy,
  • R 3 and R 4 mean the same or different, independently of one another
  • -C 6 alkyl optionally substituted with fluorine, chlorine, hydroxy, amino, mercapto, C *, - C 4 - acyloxy, benzoyloxy, benzyloxy, phenoxy, C r C 4 alkoxy, C r C 4 alkylamino, di ( C r C 4 alkyl) amino, C *, C 4 alkylthio, C - C 4 alkylsulfinyl, carboxy,
  • one of the radicals R 3 or R 4 can be hydrogen
  • R 3 and R 4 or R 3 and Y can also also also also also also also also also also also
  • alkyl groups mentioned in the preceding definitions can be straight-chain or branched. Unless otherwise defined, they preferably contain 1 to 8, particularly preferably 1 to 6, in particular 1 to 4, carbon atoms. Examples are the methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1, 1-dimethylethyl group and the like.
  • alkenyl groups mentioned in the preceding definitions can be straight-chain or branched and contain 1 to 3 double bonds. Unless otherwise defined, these groups preferably contain 2 to 8, in particular 2 to 6, carbon atoms. Examples are the 2-propenyl, 1-methylethenyl, 2-butenyl, 3-butenyl, 2-methyl-2-propenyl, 3-methyl-2-butenyl, 2,3-dimethyl-2-butenyl -, 3,3-dichloro-2-propenyl and pentadienyl groups and the like.
  • alkynyl groups mentioned in the preceding definitions can be straight-chain or branched and contain 1 to 3 triple bonds. Unless otherwise defined, they preferably contain 2 to 8, particularly preferably 3 to 6, carbon atoms. Examples are the 2-propynyl and 3-butynyl groups and the like. Unless otherwise defined, the cycloalkyl and cycloalkenyl groups mentioned in the preceding definitions preferably contain 3 to 8, particularly preferably 4 to 6, carbon atoms. Examples are the cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl or cyclohexenyl group.
  • acyl groups mentioned in the preceding definitions can be aliphatic, cycloaliphatic or aromatic. Unless otherwise defined, they preferably contain 1 to 8, particularly preferably 2 to 7, carbon atoms.
  • exemplary acyl groups are the formyl, acetyl, chloroacetyl, trifluoroacetyl, hydroxyacetyl, glycyl, propionyl, butyryl, isobutyryl, pivaloyl, cyclohexanoyl or benzoyl group.
  • aromatic groups with 6 to 14 carbon atoms, in particular with 6 to 10 carbon atoms, such as, for example, phenyl and naphthyl, are preferred.
  • heterocyclic rings or heteroaryl groups suitable heteroatoms are in particular, for example, O, S, N, where in the case of a N-containing ring saturated at this point NZ is present, in which Z, H or R 2 have the respective definitions described above means.
  • the heterocyclic rings preferably have 1 to 15 C atoms and 1 to 6 heteroatoms, in particular 3 to 11 C atoms and 1 to 4 heteroatoms.
  • heterocyclic rings or heteroaryl groups mentioned in the preceding definitions for example thiophene, furan, pyridine, pyrimidine, indole, quinoline, isoquinoline, oxazole, isoxazole, thiazole or isothiazole are suitable.
  • the aralkyl groups listed in the previous definitions are, for example, benzyl, phenylethyl, naphthylmethyl or styryl.
  • the abovementioned substituents R1 to R8 are preferably 3 times, particularly preferably 2 times, in particular simply substituted with the substituents specified in each case.
  • compounds of the formulas I, Ia, Ib and Ic can have several asymmetric carbon atoms.
  • the invention therefore relates both to the pure stereoisomers and mixtures thereof, such as. B. the associated racemate.
  • the pure stereoisomers of the compounds of the formulas I, Ia, Ib and Ic can be prepared directly or subsequently separated by known methods or in analogy to known methods.
  • the subject of the present invention further includes a process for the preparation of compounds of the formulas I, la, Ib and Ic as explained above under 1) - 5), characterized in that
  • R 9 has the meanings given above under 1) - 5) for R 2 , R 8 , R 7 and R 8 with the exception of hydrogen and Z is a leaving group
  • Alkyl optionally substituted with fluorine, chlorine, bromine, iodine, cyano, amino,
  • Alkenyl optionally substituted with fluorine, chlorine, bromine, iodine, cyano, amino,
  • Alkynyl optionally substituted with fluorine, chlorine, bromine, iodine, cyano, amino,
  • Cycloalkyl optionally substituted with fluorine, chlorine, bromine, iodine, cyano,
  • Cycloalkenyl optionally substituted with fluorine, chlorine, bromine, iodine, cyano,
  • Alkylcarbonyl optionally substituted with fluorine, chlorine, bromine, iodine, cyano,
  • Alkenylcarbonyl optionally substituted by fluorine, chlorine or hydroxy
  • heteroaryl heteroarylalkyl, heteroarylalkenyl, heteroarylalkylcarbonyl or
  • Heteroarylalkenylcarbonyl can be reacted in the presence of a dehydrating agent or that
  • the reaction is advantageously carried out in a solvent.
  • a solvent are suitable for.
  • aromatic hydrocarbons such as toluene or xylene, water, lower alcohols such as methanol, ethanol, methyl glycol or 1-butanol, ethers such as tetrahydrofuran or glycol dimethyl ether, basic solvents such as pyridine or N-methylimidazole, carboxylic acids such as acetic acid or mixtures of these solvents.
  • the presence of a suitable acidic or basic catalyst e.g. B. p-toluenesulfonic acid, acetic acid, mineral acids or salts such as sodium acetate, sodium carbonate, potassium carbonate or pyridinium hydrochloride is favorable.
  • the reaction temperature can be between 0 and 200 ° C, preferably at the boiling point of the solvent.
  • the above-mentioned method B preferably proceeds under the following conditions:
  • the substituent Z in formula IV is a suitable leaving group, such as. As chlorine, bromine or iodine, a suitable radical of sulfuric acid, an aliphatic or aromatic sulfonic acid ester or optionally halogenated acyloxy.
  • the reaction is conveniently carried out in a solvent in the presence of a suitable base to collect the acid liberated in the reaction.
  • Aromatic hydrocarbons such as toluene or xylene, lower alcohols such as methanol, ethanol, methyl glycol or 1-butanol, ethers such as tetrahydrofuran or glycol dimethyl ether, dipolar can be used as solvents aprotic solvents such as N, N-dimethyformamide, N-methylpyrolidone, acetonitrile, nitrobenzene, dimethyl sulfoxide or mixtures of these solvents.
  • Suitable bases are e.g. B.
  • alkali or alkaline earth metal carbonates or bicarbonates such as sodium hydrogen carbonate, sodium carbonate or calcium carbonate
  • alkali or alkaline earth metal hydroxides such as potassium hydroxide or barium hydroxide
  • alcoholates such as sodium ethanolate or potassium tert-butoxide
  • organolithium compounds such as butyllithium or lithium diisopropylamide
  • alkali or alkaline earth metal such as sodium hydroxide Calcium hydride
  • alkali metal fluorides such as potassium fluoride or an organic base such as triethylamine or pyridine.
  • phase transfer catalyst such as B. benzyltriethylammonium chloride are possible.
  • an iodine salt e.g. B. lithium iodide attached.
  • the reaction is usually carried out at temperatures between -10 and 160 ° C, preferably at room temperature or the boiling point of the solvent.
  • nucleophilic substituents such as. B. hydroxyl, mercapto or amino groups before carrying out the reaction in a suitable manner or with common protective groups such as. B. acetyl or benzyl.
  • the preferred sulfurization reagent is 2,4-bis (4-methoxyphenyl) -1, 3-dithia-2,4-diphosphetane-2,4-disulfide (Lawesson's reagent), bis (tricyclohexyltin) sulfide, bis (tri-n-butyltin) sulfide, bis (triphenyltin) sulfide, bis (trimethylsilyl) sulfide or phosphorus pentasulfide.
  • the reaction is advantageously carried out in an organic solvent or a solvent mixture, at room temperature or higher, preferably at the boiling temperature of the reaction mixture and, if possible, under anhydrous conditions carried out.
  • a Lewis acid such as boron trichloride.
  • a suitable protective group e.g. B. by acetalization to protect.
  • Suitable solvents for this reaction are halogenated solvents such as
  • aromatic hydrocarbons such as toluene or xylene or mixtures of these solvents.
  • the reaction is preferably carried out at temperatures between 0 and 100 ° C., particularly preferably at room temperature.
  • cyclization described under E) takes place in a suitable solvent such as lower alcohols, e.g. As methanol, ethanol or methyl glycol, ethers, e.g. B. tetrahydrofuran or 1, 2-dimethoxyethane, dipolar aprotic solvents, e.g. B.
  • a suitable solvent such as lower alcohols, e.g. As methanol, ethanol or methyl glycol, ethers, e.g. B. tetrahydrofuran or 1, 2-dimethoxyethane, dipolar aprotic solvents, e.g. B.
  • Alkali or alkaline earth metal carbonates or bicarbonates such as sodium carbonate, calcium carbonate or sodium bicarbonate, alkali or alkaline earth metal hydroxides such as potassium hydroxide or barium hydroxide, alcoholates such as sodium ethanolate or potassium tert-butoxide, organolithium compounds such as butyllithium or lithium diisopropylamide or alkali metal or alkaline earth metal or alkali metal or alkaline earth metal are suitable Calcium hydride or an organic base such as triethylamine or pyridine - the latter can also be used as solvents, or organic or inorganic acids such as acetic acid, trifluoroacetic acid, 36
  • the reaction is preferably carried out at temperatures between -10 and 120 ° C, particularly preferably at room temperature.
  • the substituent Z in formula VI is equal to hydroxy, alkoxy, chlorine, or bromine
  • the starting materials of the general formulas II, IIA, IIB or IIC are known from the literature or can be prepared by methods described in the literature.
  • the synthesis goes z. B. from azaisato anhydrides from the formula VII, which are reacted with compounds of the formula VIIa to give the derivatives of the general formula II, IIIa, IIb or IIc (see US Pat. No. 3,887,550 (1975), US Pat. No. 3,947,416 (1976), GM Coppola et al., J. Heterocyclic Chemistry 22, 193 (1985) and GM Coppola, Synthesis 1980, 505 and the literature cited therein).
  • M in formula VIIa represents the metal atom or a metal atom equivalent, preferably an alkaline earth metal or alkali metal, preferably lithium.
  • the medicaments according to the invention can be used enterally (orally), parenterally (intravenously), rectally, subcutaneously, intramuscularly or locally (topically). They can be administered in the form of solutions, powders (tablets, capsules including microcapsules), ointments (creams or gels) or suppositories.
  • the auxiliaries for such formulations are the pharmaceutically customary liquid or solid fillers and extenders, solvents, emulsifiers, lubricants, taste correctives, colorants and / or buffer substances.
  • 0.1 to 10 preferably 0.2 to 8 mg / kg body weight are administered one or more times a day.
  • the dosage units used suitably depend on the respective pharmacokinetics of the substance or the galenical preparation used.
  • the dosage unit used for the compounds according to the invention is
  • the compounds of the invention can also be used in combination with other antiviral agents, such as. B. nucleoside analogs, protease inhibitors, other RT inhibitors or adsorption inhibitors and immunostimulants, interferons, interleukins and colony stimulating factors (z. B. GM-CSF, G-CSF, M-CSF) are administered.
  • other antiviral agents such as. B. nucleoside analogs, protease inhibitors, other RT inhibitors or adsorption inhibitors and immunostimulants, interferons, interleukins and colony stimulating factors (z. B. GM-CSF, G-CSF, M-CSF) are administered.
  • Complete medium additionally contains 20% fetal calf serum and 40 lU / ml recombinant interleukin 2.
  • Lymphocytes isolated from fresh donor blood using Ficol R gradient centrifugation are cultured with the addition of 2 g / ml phytohemagglutinin (Wellcome) in complete medium for 36 h at 37 ° C under 5% CO2. After adding 10% DMSO, the cells are frozen at a cell density of 5 ⁇ 10 6 and stored in liquid nitrogen. For the experiment, the cells are thawed, washed in the RPMI medium and cultured in the complete medium for 3 to 4 days.
  • test preparations were dissolved in a concentration of 16.7 mg / ml in DMSO and diluted to 1 mg / ml in complete medium.
  • Lymphocyte cultures with a cell count of 5 x 10 5 cells / ml were carried out
  • the infected lymphocytes were centrifuged at 37 ° C. and in the same
  • the infected cell cultures were examined under the microscope for the presence of giant cells which indicate an active virus multiplication in the culture.
  • the lowest preparation concentration at which no giant cells appeared was determined as the inhibitory concentration against HIV.
  • the supernatants from the culture plates were checked accordingly with the aid of an HIV antigen test 39 determined by the manufacturer (Organon) for the presence of HIV antigen.
  • RT reverse transcriptase
  • SPA scintillation proximity assay
  • the reagent kit for the RT-SPA was obtained from Amersham / Buchler (Braunschweig).
  • the enzyme RT (cloned from HIV in E. coli) was from HT-Biotechnology LTD, Cambridge, UK. Approach:
  • bovine serum albumin was added to the "assay" buffer at the final concentration of 0.5 mg / ml.
  • the test was carried out in Eppendorf reaction vessels with a 100 ml batch volume.
  • the manufacturer's RT concentrate (5000 U / ml) was dissolved in Tris-HCl buffer 20 mM; pH 7.2; Diluted 30% glycerol to an activity of 15 U / ml, the incubation time for the batches was 60 min (37 ° C.).
  • the inhibitor stock solutions were further diluted in Tris-HCl buffer, 50 mM, pH 8 and tested in suitable concentrations.
  • the concentration associated with 50% enzyme inhibition was determined from the graphical representation of RT activity versus log C * nh .
  • a lithium diisopropyl amide solution is prepared by reacting 100 mmol diisopropylamine in 50 ml absolute tetrahydrofuran with 100 mmol 1.6 molar n-butyl lithium solution in n-hexane at -78 ° C. 5.4 ml (40 mmol) of ethyl isobutyrate are added dropwise to this solution at a temperature of -78 ° C. in the course of 30 minutes. After the addition has ended, the reaction mixture is stirred at 0 ° C. for a further 30 minutes.
  • the less polar fraction 1 is 3,3-dimethyl-1-n-propyl-1,8-naphthyridine-2,4 (1 H, 3H) -dione-4-one-propyl-oxime
  • the oil remaining after chromatography crystallizes after the addition of a little n-heptane.
  • reaction solution is concentrated under reduced pressure on a rotary evaporator and the oily residue is taken up in ethyl acetate.
  • the organic phase is washed twice with water and dried over Na 2 SO 4 . After concentrating the organic phase, a light yellow oil remains, which crystallizes after the addition of MTB ether / n-heptane.
  • a lithium diisopropylamide solution is prepared by reacting 13.6 ml (96 mmol) of diisopropylamine in 100 ml of absolute tetrahydrofuran with 96 mmol of 1.6 molar n-butyl-lithium solution in n-hexane at -78 ° C.
  • the mixture is then extracted three times with 100 ml of ethyl acetate each time and the combined organic phases are washed several times with a little water. After the organic phase has been dried using Na 2 SO 4 , the mixture is concentrated on a rotary evaporator under reduced pressure. The crude product obtained in this way is recrystallized from isopropanol.
  • O-ethyloxime (13) 200 mg (0.93 mmol) of 3-cyclopentylidene-1,8-naphthyridine-2,4 (1H, 3H) -dione (see experiment 13), dissolved in 20 ml of absolute pyridine, are mixed with 360 mg of O-ethylhydroxylamine hydrochloride and that Reaction mixture stirred at a temperature of 90 ° C for 8 hours.
  • the reaction mixture is concentrated on a rotary evaporator under reduced pressure and taken up in 200 ml of ethyl acetate.
  • the reaction product crystallizes out when the mobile phase is distilled off on a rotary evaporator.

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Abstract

Les composés de formule (I) ainsi que leurs formes tautomères de formules générales (Ia), (Ib) et (Ic) où les symboles T, U, V, W, X, Y et n, ainsi que les substituants R1 - R3, ont les significations données dans la description, ont un effet antiviral.
PCT/EP1994/003976 1993-12-24 1994-11-30 Aza-4-iminoquinoleines, leur procede de production et leur utilisation Ceased WO1995018127A1 (fr)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4347362A (en) * 1981-10-08 1982-08-31 American Home Products Corporation 1-Alkyl-4-amino-3-(3-aminotriazolo)-1,8 naphthyridine-2-ones
WO1990005523A2 (fr) * 1988-11-15 1990-05-31 The Upjohn Company Esters de phenanthrolinedicarboxylate, derives de 4-aminoquinoline et isoquinoline en tant qu'inhibiteurs de la transcriptase d'inversion de hiv
EP0509398A1 (fr) * 1991-04-15 1992-10-21 Hoechst Aktiengesellschaft Quinoxalines, procédé pour leur préparation et leur utilisation
EP0579968A1 (fr) * 1992-06-27 1994-01-26 Hoechst Aktiengesellschaft Dérivés de 4-Iminoquinoléine, procédé pour leur préparation et leur utilisation

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4347362A (en) * 1981-10-08 1982-08-31 American Home Products Corporation 1-Alkyl-4-amino-3-(3-aminotriazolo)-1,8 naphthyridine-2-ones
WO1990005523A2 (fr) * 1988-11-15 1990-05-31 The Upjohn Company Esters de phenanthrolinedicarboxylate, derives de 4-aminoquinoline et isoquinoline en tant qu'inhibiteurs de la transcriptase d'inversion de hiv
EP0509398A1 (fr) * 1991-04-15 1992-10-21 Hoechst Aktiengesellschaft Quinoxalines, procédé pour leur préparation et leur utilisation
EP0579968A1 (fr) * 1992-06-27 1994-01-26 Hoechst Aktiengesellschaft Dérivés de 4-Iminoquinoléine, procédé pour leur préparation et leur utilisation

Non-Patent Citations (15)

* Cited by examiner, † Cited by third party
Title
C. TEMPLE ET AL.: "Potential antimitotic agents", JOURNAL OF MEDICINAL CHEMISTRY, vol. 33, no. 11, 1990, WASHINGTON US, pages 3044 - 3050 *
C. TEMPLE ET AL.: "Synthesis of potential antimalarial agents", JOURNAL OF MEDICINAL CHEMISTRY, vol. 11, 1968, WASHINGTON US, pages 1216 - 1218 *
C. TEMPLE ET AL: "Synthesis of potential antimalarial agents", JOURNAL OF MEDICINAL CHEMISTRY, vol. 13, no. 5, 1970, WASHINGTON US, pages 853 - 857 *
CHEMICAL ABSTRACTS, vol. 87, no. 19, 1977, Columbus, Ohio, US; abstract no. 152167u, W. CZUBA ET AL.: "2-Hydroxy-4-hydrazine-1,7-naphthyridine" page 593; *
CHEMICAL ABSTRACTS, vol. 92, no. 9, 1980, Columbus, Ohio, US; abstract no. 76355q, W. CZUBA ET AL.: "Synthesis and amination of 2,4-dibromo-1,6-naphthyridine" page 665; *
D.J. MCCAUSTLAND ET AL.: "1,5-Naphthyridines", JOURNAL OF HETEROCYCLIC CHEMISTRY, vol. 7, no. 3, 1970, PROVO US, pages 467 - 473 *
G.B. BARLIN ET AL.: "Potential antimalarials", AUSTRALIAN JOURNAL OF CHEMISTRY, vol. 37, no. 10, 1984, EAST MELBOURNE AU, pages 2469 - 2477 *
H.J.W. VAN DEN HAAK ET AL.: "The amination of 3-bromo-2-ethoxy-1,5-naphthyridine", RECUEIL, JOURNAL OF THE ROYAL NETHERLANDS CHEMICAL SOCIETY, vol. 99, no. 3, 1980, DEN HAAG NL, pages 83 - 86 *
J. POMORSKI ET AL.: "Reactivity of derivatives of 3-bromo-1,5-naphthyridine and 3-bromoquinoline towards potassium amide in liquid ammonia", RECUEIL DES TRAVAUX CHIMIQUES DES PAYS-BAS, vol. 92, 1973, DEN HAAG NL, pages 970 - 976 *
L.H. SCHMIDT: "Appraisals of compounds of diverse chemical classes for capacities to cure infections with sporozoites of plasmodium cynomolgi", AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, vol. 32, no. 2, 1983, BALTIMORE, US, pages 231 - 257 *
POL. J. CHEM. 1978, 52(12), 2369-76 *
R.D. ELLIOTT ET AL.: "Potential folic acid antagonists", JOURNAL OF ORGANIC CHEMISTRY, vol. 31, 1966, EASTON US, pages 1890 - 1894 *
R.D. ELLIOTT ET AL.: "The isomeric pyridopyrazines from the reaction of some tetraaminopyridines with pyruvaldehyde and benzyl", JOURNAL OF ORGANIC CHEMISTRY, vol. 33, no. 6, 1968, EASTON US, pages 2393 - 2397 *
R.D. ELLIOTT: "Potential folic acid antagonists", JOURNAL OF ORGANIC CHEMISTRY, vol. 33, no. 2, 1968, EASTON US, pages 533 - 536 *
V. OAKES ET AL.: "Polyazanaphthalenes", JOURNAL OF THE CHEMICAL SOCIETY, 1958, LETCHWORTH GB, pages 204 - 208 *

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