Patent EA-001428-B1 (EA)
Title: Pyrrolopyrimidines and pharmaceutical compositions
Inventor: TRAXLER PETER
IPC: A61P43/00
Filed: 1996-06-24
Abstract: 1. A 7H-pyrrolo[2,3-d]pyrimidine derivative of formula I:   wherein q is 0 or 1; n is from 1 to 3 when q is 0, or n is from 0 to 3 when q is 1; R is halogen, C1-C7 alkyl, hydroxy, C1-C7 alkanoyloxy, C1-C7 alkoxy, carboxy, C1-C7 alkoxycarbonyl, carbamoyl, N-C1-C7 alkylcarbamoyl, N,N-di-C1-C7 alkylcarbamoyl , cyano, amino, C1-C7 alkanoylamino, C1-C7 alkylamino, N,N-di-C1-C7 alkylamino or tri-fluoromethyl, it being possible when several radicals R are present in the molecule for those radicals to be identical or different, a) R1 and R2 are each independently of each other α) phenyl substituted by carbamoylmethoxy-, carboxymethoxy-, benzyloxycarbonylmethoxy group, C1-C7 alkoxycarbonylmethoxy group, phenyl, amino-, C1-C7 alkanoylamino-, C1-C7 alkylamino-, N,N-di-C1-C7 alkylamino-, hydroxy, C1-C7 alkanoyloxy-, carboxy group, C1-C7-alkoxycarbonyl, carbamoyl, N-C1-C7 alkylcarbamoyl, N,N-di-C1-C7-alkylcarbamoyl , cyano or by nitro group; β) hydrogen; () unsubstituted or halo- or C1-C7 alkylsubstituted pyridyl; δ) N-benzylpyridinium-2-yl; naphthyl; cyano; carboxy; C1-C7 alkoxycarbonyl; carbamoyl; N-C1-C7 alkylcarbamoyl; N,N-di-C1-C7 alkylcarbamoyl; N-benzylcarbamoyl; formyl; C1-C7 alkanoyl; C1-C7 alkenyl; C1-C7 alkenyloxy; or ε) C1-C7 alkyl substituted by εα) halogen, amino, C1-C7 alkylamino, piperazino, di-C1-C7-alkylamino, εβ) phenylamino that is unsubstituted or substituted in the phenyl moiety by halogen, C1-C7 alkyl, hydroxy-, C1-C7 alkanoyloxy-, C1-C7 alkoxy-, carboxy group, C1-C7 alkoxycarbonyl, carbamoyl, N-C1-C7 alkylcarbamoyl, N,N-di-C1-C7 alkylcarbamoyl, cyano, amino, C1-C7-alkanoylamino, C1-C7 alkylamino, N,N-di-C1-C7 alkylamino or by trifluoromethyl; ε() hydroxyl, C1-C7 alkoxyl, cyano, carboxyl, C1-C7-alkoxycarbonyl, carbamoyl, N-C1-C7 alkylcarbamoyl, N,N-di-C1-C7-alkylcarbamoyl, mercapto or εδ) by a radical of the formula R3-S(O)m- wherein R3 is C1-C7 alkyl and m is 0, 1 or 2, or b) when q is 0, one of the radicals R1 and R2 is unsubstituted C1-C7-alkyl or unsubstituted phenyl and the other of the radicals R1 and R2 has one of the meanings given above in paragraph a) with the exception of hydrogen, or c) when q is 1, R1 and R2 are each independently of the other unsubstituted C1-C7 alkyl or unsubstituted phenyl or have one of the meanings given above in paragraph a), and R6 is hydrogen, C1-C7 alkyl, C1-C7 alkoxycarbonyl, carbamoyl, N-C1-C7-alkylcarbamoyl or N,N-di-C1-C7 alkylcarbamoyl, or a salt thereof, with the exception of the compound of formula I wherein n is 0 or 2, q is 1, R1 and R6 are each hydrogen, R2 is methyl, and R is 3,4-methoxy group. 2. A compound of formula I according to claim 1 wherein q is 0 or 1; n is from 1 to 3 when q is 0, or n is from 0 to 3 when q is 1, R is halogen, C1-C7 alkyl, hydroxy, C1-C7 alkanoyloxy, C1-C7 alkoxy, carboxy, C1-C7 alkoxycarbonyl, carbamoyl, N-C1-C7 alkylcarbamoyl, N,N-di-C1-C7 alkylcarbamoyl , cyano, amino, C1-C7 alkanoylamino, C1-C7-alkylamino, N,N-di-C1-C7 alkylamino or trifluoromethyl, it being possible when several radicals R are present in the molecule for those radicals to be identical or different; a) R1 is hydrogen and R2 is phenyl substituted by carbamoylmethoxy, carboxymethoxy benzyloxycarbonylmethoxy, C1-C7 alkoxycarbonylmethoxy, phenyl, amino, C1-C7 alkanoylamino, C1-C7 alkylamino, N,N-di-C1-C7 alkylamino, hydroxy, C1-C7 alkanoyloxy, carboxy, C1-C7 alkoxycarbonyl, carbamoyl, N-C1-C7 alkylcarbamoyl, N,N-di-C1-C7 alkylcarbamoyl, cyano or by nitro; unsubstituted or halo- or C1-C7 alkyl-substituted pyridyl; N-benzylpyridinium-2-yl; naphthyl; cyano; carboxy; C1-C7 alkoxycarbonyl; carbamoyl; N-C1-C7 alkylcarbamoyl; N,N-di-C1-C7-alkylcarbamoyl ; N-benzylcarbamoyl; formyl; C1-C7 alkanoyl; C1-C7 alkenyl; C1-C7 alkenyloxy; or C1-C7 alkyl substituted by halogen; phenylamino that is unsubstituted or substituted in the phenyl moiety by halogen, C1-C7 alkyl, C1-C7 alkanoyloxy, hydroxy, C1-C7 alkoxy, carboxy, C1-C7 alkoxycarbonyl, carbamoyl, N-C1-C7 alkylcarbamoyl, N,N-di-C1-C7 alkylcarbamoyl, cyano, amino, C1-C7 alkanoylamino, C1-C7 alkylamino, N,N-di-C1-C7 alkylamino or by trifluoromethyl; C1-C7 alkoxy, cyano, carboxy, C1-C7 alkoxycarbonyl, carbamoyl, N-C1-C7 alkylcarbamoyl, N,N-di-C1-C7 alkylcarbamoyl, mercapto or by a radical of the formula R3-S(O)m- wherein R3 is C1-C7 alkyl and m is 0, 1 or 2, or b) when q is 0, one of the radicals R1 and R2 is unsubstituted C1-C7 alkyl or unsubstituted phenyl and the other of the radicals R1 and R2 has one of the meanings given above in paragraph a) with the exception of hydrogen, or c) when q=1, R1 is hydrogen and R2 is unsubstituted phenyl and R6 is hydrogen, C1-C7 alkyl, C1-C7 alkoxycarbonyl, carbamoyl, N-C1-C7-alkylcarbamoyl or N,N-di-C1-C7 alkylcarbamoyl, or a salt thereof. 3. A compound of formula I according to claim 1 wherein q is 0 or 1, n is from 1 to 3 when q is 0, or n is from 0 to 3 when q is 1, R is halogen, C1-C7 alkyl, hydroxy, C1-C3 alkanoyloxy, C1-C7 alkoxy, carboxy, C1-C7 alkoxycarbonyl, carbamoyl, N-C1-C7 alkylcarbamoyl, N,N-di-C1-C7 alkylcarbamoyl , cyano, amino, C1-C7 alkanoylamino, C1-C7 alkylamino, N,N-di-C1-C7 alkylamino or trifluoromethyl, it being possible when several radicals R are present in the molecule for those radicals to be identical or different, a) R1 and R2 are each independently of the other phenyl substituted by carbamoylmethoxy, carboxymethoxy, benzyloxycarbonylmethoxy, C1-C7 alkoxycarbonylmethoxy, phenyl, amino, C1-C7 alkanoylamino, C1-C7-alkylamino, N,N-di-C1-C7 alkylamino, hydroxy, C1-C7 alkanoyloxy, carboxy, C1-C7 alkoxycarbonyl, carbamoyl, N-C1-C7 alkylcarbamoyl, N,N-di-C1-C7 alkylcarbamoyl, cyano or by nitro; hydrogen with proviso that R1 and R2 can not be hydrogens at the same time ; unsubstituted or halo- or C1-C7 alkylsubstituted pyridyl; N-benzylpyridinium-2-yl; naphthyl; cyano; carboxy; C1-C7 alkoxycarbonyl; carbamoyl; N-C1-C7 alkylcarbamoyl; N,N-di-C1-C7 alkylcarbamoyl; N-benzylcarbamoyl; formyl; C1-C7 alkanoyl; C1-C7 alkenyl; C1-C7 alkenyloxy; or C1-C7 alkyl substituted by halogen, amino, C1-C7 alkylamino, piperazino, di-C1-C7 alkylamino, piperazino, di-C1-C7 alkylamino, hydroxy, C1-C7 alkoxy, cyano, carboxy, C1-C7 alkoxycarbonyl, carbamoyl, N-C1-C7 alkylcarbamoyl, N,N-di-C1-C7 alkylcarbamoyl, mercapto or by a radical of the formula R3-S(O)m- wherein R3 is C1-C7 alkyl and m is 0, 1 or 2, or b) when q is 0, one of the radicals R1 and R2 is unsubstituted C1-C7 alkyl or unsubstituted phenyl and the other of the radicals R1 and R2 has one of the meanings given above in paragraph a) with the exception of hydrogen, or c) when q is 1, R1 and R2 are each independently of the other unsubstituted C1-C7 alkyl or unsubstituted phenyl or have one of the meanings given above in paragraph a), and R6 is hydrogen, C1-C7 alkyl, C1-C7 alkoxycarbonyl, carbamoyl, N-C1-C7-alkylcarbamoyl or N,N-di-C1-C7 alkylcarbamoyl, or a salt thereof, with the exception of the compound of formula I wherein n is 0 or 2, q is 1, R1 and R6 are each hydrogen and R2 is methyl, and R is 3,4-methoxy group. 4. 4. A compound of formula I according to claim 1 wherein q is 0 or 1; n is from 1 to 3, when q=0 or n is from 0 to 3, when q=1; R is halogen, C1-C7 alkyl, hydroxy, C1-C7 alkanoyloxy, C1-C7 alkoxy, carboxy, C1-C7 alkoxycarbonyl, carbamoyl, N-C1-C7 alkylcarbamoyl, N,N-di-C1-C7 alkylcarbamoyl , cyano, amino, C1-C7 alkanoylamino, C1-C7 alkylamino, N,N-di-C1-C7 alkylamino or trifluoromethyl, it being possible when several radicals R are present in the molecule for those radicals to be identical or different; R1 is hydrogen or C1-C7 alkyl which is unsubstituted or substituted by di-C1-C7 alkylamino group, and R2 is phenyl, which is substituted by carbamoylmethoxy, carboxymethoxy, benzyloxocarbonylmethoxy, C1-C7 alkoxycarbonylmethoxy, C1-C7 alkoxycarbonyl, carboxy, N,N-di-C1-C7-alkylcarbamoyl, phenyl, amino, C1-C7 alkylamino, di-C1-C7 alkylamino, C1-C7 alkanoylamino, hydroxy or nitro group; R6 is hydrogen, C1-C7 alkyl, C1-C7 alkoxycarbonyl, carbamoyl, N-C1-C7alkylcarbamoyl or N,N-di-C1-C7 alkylcarbamoyl, or salts thereof, with the exception of the compound of formula I, n is 0 or 2, q is 1, R1 and R2 are each hydrogen and R2 is methyl, and R is 3,4-methoxy. 5. A compound of formula I according to claim 1 wherein q is 0, n is from 1 to 3, R is halogen, C1-C7 alkyl, hydroxy, C1-C7 alkanoyloxy, C1-C7 alkoxy, carboxy, C1-C7 alkoxycarbonyl, carbamoyl, N-C1-C7 alkylcarbamoyl, N,N-di-C1-C7 alkylcarbamoyl , cyano, amino, C1-C7 alkanoylamino, C1-C7 alkylamino, N,N-di-C1-C7 alkylamino or trifluoromethyl, it being possible when several radicals R are present in the molecule for those radicals to be identical or different; a) R1 and R2 are each independently of the other phenyl substituted by phenyl, amino, C1-C7 alkanoylamino, C1-C7 alkylamino, N,N-di-C1-C7 alkylamino, hydroxy, C1-C7 alkanoyloxy, carboxy, C1-C7 alkoxycarbonyl, carbamoyl, N-C1-C7 alkylcarbamoyl, N,N-di-C1-C7 alkylcarbamoyl, cyano or by nitro; hydrogen, with provizo that R1 and R2 can not be hydrogens at the same time; unsubstituted or halo- or C1-C7 alkylsubstituted pyridyl; N-benzylpyridinium-2-yl; naphthyl; cyano; carboxy; C1-C7 alkoxycarbonyl; carbamoyl; N-C1-C7 alkylcarbamoyl; N,N-di-C1-C7 alkylcarbamoyl ; formyl; C1-C7 alkanoyl; C1-C7 alkenyl; C1-C7 alkenyloxy; or C1-C7 alkyl substituted by halogen, amino, C1-C7 alkylamino, piperazino, di-C1-C7 alkylamino, hydroxy, C1-C7 alkoxy, cyano, carboxy, C1-C7 alkoxycarbonyl, carbamoyl, N-C1-C7 alkylcarbamoyl , N,N-di-C1-C7 alkylcarbamoyl, mercapto or by a radical of the formula R3-S(O)m-wherein R3 is C1-C3 alkyl and m is 0, 1 or 2, or b) one of the radicals R1 and R2 is unsubstituted C1-C7 alkyl or unsubstituted phenyl and the other of the radicals R1 and R2 has one of the meanings given above in paragraph a) with the exception of hydrogen, or a salt thereof. 6. A compound of formula I according to claim 1 wherein q is 0, n is 1 or 2, R is