Patent IL-117810-A (IL)
Title: N-substituted azaheterocyclic carboxylic compounds and pharmaceutical compositions containing them for treating neurogenic pain or inflammation, or diabetic neuropathy
IPC: C07D453/02
Filed: 1996-04-03
Abstract: Compounds of the formula wherein R1 and R2 independently are hydrogen, halogen, trifluoromethyl, NR6R7, hydroxy, C1-6-alkyl or C1-6-alkoxy; and Y is LN-CH2, LCH-CH2 or L-C=CH- wherein only the underscored atom participates in the ring system; and X is -O-, -S-, C(R6R7)-, -CH2CH2-, -CH=CH-CHS2, -CH2-CH=CH-, -CH2-(C=O)-, -(C=O)-CH2-, -CH2CH2CH2-, -CH=CH-, -N(R8)-(C=O)-, -(C=O)-N(R8)-, -O-CH2-, -CH2-O-, -S- CH2-, -CH2-S- -(C=O)-, N(R9)- or -(S=O)- wherein R6, R7, R8 and R9 independently are hydrogen or C1-6-alkyl; and r is 1, 2 or 3; and Z is 2129 כ" ה באלול התשס" א - September 13, 2001 wherein R3 is -(CH2)mOH or -(CH2)pCOR4 wherein m is 0, 1, 2, 3, 4, 5 or 6 and p is 0 or 1 and wherein R4 is -OH, -NH2, -NHOH or C1-6-alkoxy; and R10 is hydrogen, C1-6-alkyl, C1-6-alkoxy or phenyl optionally substituted with halogen, trifluoromethyl, hydroxy, C1-6-alkyl or C1-6-alkoxy; and - - - is optionally a single bond or a double bond, with the proviso that if R1 and R2 independently are hydrogen or halogen; Y is LN-CH2-; X is -S- and R10 is hydrogen, then R3 cannot be -(CH2)pCOR4 wherein p is 0 and R4 is -NH2- NHOH or C1-6 alkoxy; and further if R1 and R2 independently are hydrogen, halogen, trifluoromethyl, C1-6 - alkyl or C1-6- alkoxy; X is -O-, -S-, -C(R6R7)-, -CH2CH2-, -CH=CH-CH2-, -CH2-CH= CH-,- CH2CH2CH2-, -CH=CH-, N(R8)-(C=O)-, -(C=O)-N(R8)-, -O-CH2-, -CH2-O-, -S-CH2-, CH2-S-, -(C=O)- or -(S=O)- and R10 is hydrogen, then R3 cannot be -(CH2)pCOR4 wherein p is 0 and R4 is -OH or C1-6 - alkoxy; or Z is selected from wherein R3 is -(CH2)mOH or -(CH2)pCOR4 wherein m is 0, 1, 2, 3, 4, 5 or 6 and p is 0 or 1 and wherein R4 is -OH, -NH2, -NHOH or C1-6 - alkoxy; and R5 is hydrogen, halogen, trifluoromethyl, hydroxy, C1-6-alkyl or C1-16 alkoxy; and - - - is optionally a single bond or a double bond, with the proviso that if R1 and R2 independently are hydrogen or halogen; Y is L N-CH2-; X is -S- and R5 is hydrogen, then R3 cannot be -(CH2)pCOR4 wherein p is 0 and R4 is -NH2, -NHOH or C1-6-alkoxy; or Z is selected from 2130 כ" ה באלול התשס" א - September 13, 2001 wherein n is 1 or 2; and R3 is -(CH2)mOH or -(CH2)pCOR4 wherein m is 0, 1, 2, 3, 4, 5 or 6 and p is 0 or 1 and wherein R4 is -OH, -NH2, -NHOH or C1-6-alkoxy; and R11 is hydrogen or C1-6-alkyl; or Z is wherein R3 is -(CH2)mOH or -(CH2)pCOR4 wherein m is 0, 1, 2, 3, 4, 5 or 6 and p is 0 or 1 and wherein R4 is -OH, -NH2 -NHOH or C1-6-alkoxy; with the proviso that if R1 and R2 independently are hydrogen, halogen or trifluoromethyl; Y is LN-CH2- and X is -S-, then R3 cannot be -(CH2)mOH wherein m is 0; and further if R1 and R2 independently are hydrogen, halogen, trifluoromethyl, C1-6-alkyl or C1-6-alkoxy and X is -O-, -S-, -C(R6R7)-, -CH2CH2-, -CH=CH-CH2-, -CH2-CH=CH-, -CH2CH2CH2-, -CH=CH-, -N(R8)-(C=O)-, -(C=O)-N(R8)-, -O-CH2-, -CH2-O-, -S- CH2-, -CH2-S-, -(C=O)- or (S=O), then R3 cannot be -(CH2)pCOR4 wherein p is 1 and R4 is -OH or C1-6-alkoxy; or wherein R10 is hydrogen, C1-6-alkyl, C1-6-alkoxy or phenyl optionally substituted with halogen, trifluoromethyl, hydroxy, C1-6-alkyl or C1-6-alkoxy; with the proviso that if R1 and R2 independently are hydrogen or halogen; Y is LN-CH2-; X is -CH=CH- and r is 1, 2 or 3, then R10 cannot be phenyl optionally substituted; and further if R1 and R2 are hydrogen; Y is LC=CH; X is -CH2-CH2- or -CH=CH- and r is 1, 2 or 3, then R10 cannot be phenyl substituted with trifluoromethyl; or Z is 2131 כ" ה באלול התשס" א - September 13, 2001 wherein R3 is -(CH2)mOH or -(CH2)pCOR4 wherein m is 0, 1, 2, 3, 4, 5 or 6 and p is 0 or 1 and wherein R4 is -OH, -NH2, -NHOH or C1-6-alkoxy; with the proviso that if R1 and R2 are hydrogen; Y is LN- CH2-; X is -CH=CH- and r is 2, then R3 cannot be -(CH2)mOH wherein m is 1; or pharmaceutically acceptable salts thereof.