Nova Patents
EP0349949A2

Benzodiazepine derivatives.

Abstract

A compound of the formula : wherein R' is halogen, heterocyclic group which may have one or more suitable substituent(s), aryl which may have one or more suitable substituent(s), -NH-R5 (in which R5 is hydrogen, lower alkanoyl or hydroxy(lower)alkyl),-S-R6 (in which R6 is lower alkyl, lower alkyl substituted with carboxy and amino, lower alkyl substituted with protected carboxy and protected amino, or pyridyl),-O-R7 (in which R7 is hydrogen, hydroxy protective group, lower alkyl, lower alkenyl, ar(lower)alkyl, halo-(lower)alkyl, amino(loweralkyl, protected amino(lower)alkyl, or piperazinyl(lower)alkyl which may have lower alkyl),-CONH-R$ (in which R8 is cyano, carbamoyl(lower)alkyl, carboxy(lower)alkyl, protected carboxy(lower)alkyl, or lower alkyl substituted with carbamoyl and aryl ), or-Z-R9 [in which R9 is hydrogen or lower alkyl, and Z is (wherein is hydroxy, lower alkoxy or amino) or (wherein R11 is carboxy or protected carboxy and R'2 is hydrogen; or R11 is halogen and R'2 is halogen)], R2 is aryl which may have one or more suitable substituent(s),R3 is hydrogen or halogen,R4 is hydrogen, halogen or lower alkoxy andA is lower alkylene,and a pharmaceutically acceptable salt thereof, processes for the preparation and pharmaceutical compositions comprising them as an active ingredient

EP0349949A2, drawing sheet 1
Sheet 1 of 87

Term

Term ended

Projected expiry passed 1 July 2009, 17.2 years ago.

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12 claims: 2 independent, 10 dependent

  1. 1
    A compound of the formula :. wherein R' is halogen, heterocyclic group which may have one or more suitable substituent(s), aryl which may have one or more suitable substituent(s), -NH-R5 (in which R5 is hydrogen, lower alkanoyl or hydroxy(lower)alkyl), -S-R6 (in which R6 is lower alkyl, lower alkyl substituted with carboxy and amino, lower alkyl substituted with protected carboxy and protected amino, or pyridyl), -0-R7 (in which R7 is hydrogen, hydroxy protective group, lower alkyl, lower alkenyl, ar(lower)alkyl, halo-(lower)alkyl, amino(lower)alkyl, protected amino(lower)alkyl, or piperazinyl(lower)alkyl which may have lower alkyl), -CONH-R8 (in which R8 is cyano, carbamoyl(lower)alkyl, carboxy(lower)alkyl, protected carboxy(lower)alkyl, or lower alkyl substituted with carbamoyl and aryl ), or -Z-R9 is hydrogen or lower alkyl, and Z is (wherein R10 is hydroxy, lower alkoxy or amino) or (wherein R" is carboxy or protected carboxy and R12 is hydrogen;or R" is halogen and R12 is halogen)], R2 is aryl which may have one or more suitable substituent(s), R3 is hydrogen or halogen, R4 is hydrogen, halogen or lower alkoxy and A is lower alkylene, and a pharmaceutically acceptable salt thereof.
  2. 7
    A process for preparing a compound of the formula :wherein R' is halogen, heterocyclic group which may have one or more suitable substituent(s), aryl which may have one or more suitable substituent(s), -NH-R5 (in which R5 is hydrogen, lower alkanoyl or hydroxy(lower)alkyl), -S-R6 (in which R6 is lower alkyl, lower alkyl substituted with carboxy and amino, lower alkyl substituted with protected carboxy and protected amino, or pyridyl), -O-R7 (in which R7 is hydrogen, hydroxy protective group, lower alkyl, lower alkenyl, ar(lower)alkyl, halo-(lower)alkyl, amino(lower)alkyl, protected amino(lower)alkyl, or piperazinyl(lower)alkyl which may have lower alkyl), -CONH-R8 (in which R8 is cyano, carbamoyl(lower)alkyl, carboxy(lower)alkyl, protected carboxy(lower)alkyl, or lower alkyl substit7uted with carbamoyl and aryl), or -Z-R9 [in which R9 is hydrogen or lower alkyl, and Z is (wherein R10 is hydroxy, lower alkoxy or amino) or (wherein R11 is carboxy or protected carboxy and R'2 is hydrogen;or R" is halogen and R12 is halogen)],R2 is aryl which may have one or more suitable substituent(s),R3 is hydrogen or halogen,R4 is hydrogen, halogen or lower alkoxy andA is lower alkylene,or a salt thereof,which comprises (1) reacting a compound of the formula : wherein R2, R3 and R4 are each as defined above, or a salt thereof with a compound of the formula : X-A-R' whereinR1 and A are each as defined above, andX is halogen,or a salt thereof to give a compound of the formula : wherein R1, R2, R3, R4 and A are each as defined above, or a salt thereof, or(2) reacting a compound of the formula : wherein R1, R2, R3 and A are each as defined above, or its reactive derivative at the amino group or a salt thereof with a compound of the formula : wherein R4 is as defined above, or its reactive derivative at the carboxy group or a salt thereof to give a compound of the formula : wherein R', R2, R3, R4 and A are each as defined above, or a salt thereof, or(3) subjecting a compound of the formula : wherein R2, R3, R4 and A are each as defined above, R'4 is hydrogen or lower alkyl,R'5 is an imino protective group,J is CH or N andQ is CH or N, or a salt thereof to elimination reaction of the imino protective group to give a compound of the formula : wherein R2, R3, R4, R14, A, J and Q are each as defined above, or a salt thereof.
Independent claims2