US 2003/0149000 A1 · Method for the treatment of disorders associated with apoptosis using N-heterocyclic glyoxylamide compounds

Abstract

A method or composition is disclosed for the treatment of disorders associated with apoptosis using N-heterocyclic glyoxylamide compounds.

Claims29

Dependent claims

A method of treatment of a mammal currently afflicted with disorders associated with apoptosis or previously afflicted with disorders associated with apoptosis, said method comprising administering to said mammal a therapeutically effective amount of an N-heterocyclic glyoxylamide compound represented by the formula (I) or a pharmaceutically acceptable salt, solvate, or prodrug derivative thereof:

34
wherein;
E and F are differently C or N;
--- is presence or absence of a double bond;
each X is independently oxygen or sulfur;
R11 is selected from groups (a), (b) and (c) where;
(a) is C7-C20 alkyl, C7-C20 alkenyl, C7-C20 alkynyl;
or carbocyclic radical selected from the group cycloalkyl, cycloalkenyl, phenyl, naphthyl, norbornanyl, bicycloheptadienyl, tolyl, xylyl, indenyl, stilbenyl, terphenylyl, diphenylethylenyl, phenyl-cyclohexenyl, acenaphthylenyl, and anthryl, biphenyl, bibenzylyl and related bibenzylyl homologues represented by the formula (bb),
35
where
n is a number from 1 to 8;
or
(b) is a member of (a) substituted with one or more independently selected non-interfering substituents selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C7-C12 aralkyl, C7-C12 alkaryl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, phenyl, tolyl, xylyl, biphenyl, C1-C6 alkoxy, C2-C6 alkenyloxy, C2-C6 alkynyloxy, C2-C12 alkoxyalkyl, C2-C12 alkoxyalkyloxy, C2-C12 alkylcarbonyl, C2-C12 alkylcarbonylamino, C2-C12 alkoxyamino, C2-C12 alkoxyaminocarbonyl, C1-C12 alkylamino, C1-C6 alkylthio, C2-C12 alkylthiocarbonyl, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C2-C6 haloalkoxy, C1-C6 haloalkylsulfonyl, C2-C6 haloalkyl, C1-C6 hydroxyalkyl, —C(O)O(C1-C6 alkyl), —(CH2)n—O—(C1-C6 alkyl), benzyloxy, phenoxy, phenylthio, —CHO, amino, amidino, bromo, carbamyl, carboxyl, carbalkoxy, —(CH2)n—CO2H, chloro, cyano, cyanoguanidinyl, fluoro, guanidino, hydrazide, hydrazino, hydrazido, hydroxy, hydroxyamino, iodo, nitro, phosphono, —SO3H, thioacetal, thiocarbonyl, and C1-C6 carbonyl;
where n is from 1 to 8;
(c) is the group -(L1)-R81;
where, -(L1)- is a divalent linking group having the formula;
36
where,
R84 and R85 are each independently selected from hydrogen, C1-C10 alkyl, carboxyl, carbalkoxy, or halo;
p is 1 to 5,
Z is a bond, —(CH2)—, —O—, —N(C1-C10 alkyl)-, —NH—, or —S—;
and where R81 is a group selected from (a) or (b);
R12 is hydrogen, halo, C1-C3 alkyl, C3-C4 cycloalkyl, C3-C4 cycloalkenyl, —O—(C1-C2 alkyl), or —S—(C1-C2 alkyl);
R14 is hydrogen or a group, -(La)-(acidic group) wherein -(La)- is represented by the formula;
37
where
Q is selected from the group —(CH2)—, —O—, —NH—, and —S—, and R84 and R85 are each independently selected from hydrogen, C1-C10 alkyl, aryl, C1-C10 alkaryl, C1-C10 aralkyl, and halo;
R15 is hydrogen or a group, -(La′)-(acidic group) wherein -(La′)- is represented by the formula;
38
where
r is a number from 1 to 7, s is 0 or 1, and Q is selected from the group —(CH2)—, —O—, —NH—, and —S—, and R84′ and R85′ are each independently selected from hydrogen, C1-C10 alkyl, aryl, C1-C10 alkaryl, C1-C10 aralkyl, carboxy, carbalkoxy, and halo;
provided that at least one of R14 or R15 must be the group, -(La)-(acidic group) or -(La′)-(acidic group);
R16 is hydrogen, carboxyl or ester thereof;
R17 is selected from hydrogen, non-interfering substituents, selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C7-C12 aralkyl, C7-C12 alkaryl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, phenyl, tolyl, xylyl, biphenyl, C1-C6 alkoxy, C2-C6 alkenyloxy, C2-C6 alkynyloxy, C2-C12 alkoxyalkyl, C2-C12 alkoxyalkyloxy, C2-C12 alkylcarbonyl, C2-C12 alkylcarbonylamino, C2-C12 alkoxyamino, C2-C12 alkoxyaminocarbonyl, C2-C12 alkylamino, C1-C6 alkylthio, C2-C12 alkylthiocarbonyl, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C2-C6 haloalkoxy, C1-C6 haloalkylsulfonyl, C2-C6 haloalkyl, C1-C6 hydroxyalkyl, —C(O)O(C1-C6 alkyl), —(CH2)n—O—(C1-C6 alkyl), benzyloxy, phenoxy, phenylthio, —CHO, amino, amidino, bromo, carbamyl, carboxyl, carbalkoxy, —(CH2)n—CO2H, chloro, cyano, cyanoguanidinyl, fluoro, guanidino, hydrazide, hydrazino, hydrazido, hydroxy, hydroxyamino, iodo, nitro, phosphono, —SO3H, thioacetal, thiocarbonyl, and C1-C6 carbonyl;
where n is from 1 to 8.

32 more elements

A method of treatment of a mammal currently afflicted with disorders associated with apoptosis or previously afflicted with disorders associated with apoptosis, said method comprising administering to said mammal in need of such treatment a therapeutically effective amount of an N-heterocyclic glyoxylamide compound or a pharmaceutically acceptable salt, solvate, or a prodrug derivative thereof selected from the group consisting of compounds (A) through (NN):

(A) [[3-(2-Amino-1,2-dioxoethyl)-2-methyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid,
(B) dl-2-[[3-(2-Amino-1,2-dioxoethyl)-2-methyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]propanoic acid,
(C) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-2-ylmethyl)-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(D) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-3-ylmethyl)-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(E) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-4-ylmethyl)-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(F) [[3-(2-Amino-1,2-dioxoethyl)-1-[(2,6-dichlorophenyl)methyl]-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(G) [[3-(2-Amino-1,2-dioxoethyl)-1-[(4-fluorophenyl)methyl]-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(H) [[3-(2-Amino-1,2-dioxoethyl)-2-methyl-1-[(1-naphthalenyl)methyl]-1H-indol-4-yl]oxy]acetic acid,
(I) [[3-(2-Amino-1,2-dioxoethyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid,
(I′) [[3-(2-Amino-1,2-dioxoethyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid methyl ester
(J) [[3-(2-Amino-1,2-dioxoethyl)-1-[(3-chlorophenyl)methyl]-2-ethyl-1H-indol-4-yl]oxy]acetic acid,
(K) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-2-ylmethyl)-2-ethyl-1H-indol-4-yl]oxy]acetic acid,
(L) [[3-(2-amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-2-ylmethyl)-2-propyl-1H-indol-4-yl]oxy]acetic acid,
(M) [[3-(2-Amino-1,2-dioxoethyl)-2-cyclopropyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid,
(N) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-2-ylmethyl)-2-cyclopropyl-1H-indol-4-yl]oxy]acetic acid,
(O) 4-[[3-(2-Amino-1,2-dioxoethyl)-2-ethyl-1-(phenylmethyl)-1H-indol-5-yl]oxy]butanoic acid,
(P) mixtures of (A) through (O),
(Q) (8-(Carbomethoxymethyloxy)-2-ethyl-3-(o-phenylbenzyl)indolizin-1-yl)glyoxylamide,
(R) (3-Benzyl-8-(carbethoxymethyloxy)-2-ethylindolizin-1-yl)glyoxylamide,
(S) (8-(Carbethoxymethyloxy)-2-ethyl-3-(o-phenylbenzyl)indolizin-1-yl)glyoxylamide,
(T) (3-Benzyl-8-(carbethoxymethyloxy)-2-methylindolizin-1-yl)glyoxylamide,
(U) (8-(Carbethoxymethyloxy)-3-(m-chlorobenzyl)-2-ethylindolizin-1-yl)glyoxylamide,
(V) (8-Carbethoxymethyloxy-2-ethyl-3-(1-naphthylmethyl)indolizin-1-yl)glyoxylamide,
(W) (3-Benzyl-8-(t-butoxycarbonylmethyloxy)-2-ethylindolizin-1-yl)glyoxylamide,
(X) (8-(Carbmethoxymethyloxy)-2-ethyl-3-(m-trifluoromethylbenzyl)indolizin-1-yl)glyoxylamide,
(Y) (8-(Carbmethoxymethyloxy)-2-cyclopropyl-3-(o-phenylbenzyl)indolizin-1-yl)glyoxylamide,
(Z) (3-Benzyl-8-(carboxymethyloxy)-2-ethylindolizin-1-yl)glyoxylamide,
(AA) (8-(Carboxymethyloxy)-2-ethyl-3-(o-phenylbenzyl)indolizin-1-yl)glyoxylamide,
(AA′) (8-Carbomethoxymethyloxy)-2-ethyl-3-(o-phenylbenzyl)indolizin-1-yl)glyoxylamide,
(BB) (3-Benzyl-8-(carboxymethyloxy)-2-methylindolizin-1-yl)glyoxylamide,
(CC) (8-(Carboxymethyloxy)-3-(m-chlorobenzyl)-2-ethylindolizin-1-yl)glyoxylamide,
(DD) (8-(Carboxymethyloxy)-2-ethyl-3-(m-trifluoromethylbenzyl)indolizin-1-yl)glyoxylamide,
(EE) (8-Carboxymethyloxy-2-ethyl-3-(1-naphthylmethyl)indolizin-1-yl)glyoxylamide,
(FF) (8-(Carboxymethyloxy)-2-cyclopropyl-3-(o-phenylbenzyl)indolizin-1-yl) glyoxylamide,
(GG) mixtures of (Q) through (FF),
(HH) [[3-(2-Amino-1,2-dioxoethyl)-6-carboxyl-2-ethyl-1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(II) [[3-(2-Amino-1,2-dioxoethyl)-6-methoxycarbonyl-2-ethyl-1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(JJ) [[3-(2-Amino-1,2-dioxoethyl)-6-ethoxycarbonyl-2-ethyl-1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(KK) [[3-(2-Amino-1,2-dioxoethyl)-6-n-propoxycarbonyl-2-ethyl 1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(LL) [[3-(2-Amino-1,2-dioxoethyl)-6-i-propoxycarbonyl-2-ethyl-1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(MM) [[3-(2-Amino-1,2-dioxoethyl)-6-cyclopropyloxycarbonyl-2-ethyl-1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(NN) mixtures of (HH) through (MM).

39 more elements

Use of an N-heterocyclic glyoxylamide compound for the manufacture of a medicant for treating disorders associated with apoptosis in a mammal, including a human, currently afflicted with disorders associated with apoptosis or previously afflicted with disorders associated with apoptosis;

where the compound is represented by the formula (I) or a pharmaceutically acceptable salt, solvate, or prodrug derivative thereof:
43
wherein
E and F are differently C or N;
--- is presence or absence of a double bond;
each X is independently oxygen or sulfur;
R11 is selected from groups (a), (b) and (c) where;
(a) is C7-C20 alkyl, C7-C20 alkenyl, C7-C20 alkynyl;
or carbocyclic radical selected from the group cycloalkyl, cycloalkenyl, phenyl, naphthyl, norbornanyl, bicycloheptadienyl, tolyl, xylyl, indenyl, stilbenyl, terphenylyl, diphenylethylenyl, phenyl-cyclohexenyl, acenaphthylenyl, and anthryl, biphenyl, bibenzylyl and related bibenzylyl homologues represented by the formula (bb),
44
where
n is a number from 1 to 8;
or
(b) is a member of (a) substituted with one or more independently selected non-interfering substituents selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C7-C12 aralkyl, C7-C12 alkaryl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, phenyl, tolyl, xylyl, biphenyl, C1-C6 alkoxy, C2-C6 alkenyloxy, C2-C6 alkynyloxy, C2-C12 alkoxyalkyl, C2-C12 alkoxyalkyloxy, C2-C12 alkylcarbonyl, C2-C12 alkylcarbonylamino, C2-C12 alkoxyamino, C2-C12 alkoxyaminocarbonyl, C1-C12 alkylamino, C1-C6 alkylthio, C2-C12 alkylthiocarbonyl, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C2-C6 haloalkoxy, C1-C6 haloalkylsulfonyl, C2-C6 haloalkyl, C1-C6 hydroxyalkyl, —C(O)O(C1-C6 alkyl), —(CH2)n—O—(C1-C6 alkyl), benzyloxy, phenoxy, phenylthio, —CHO, amino, amidino, bromo, carbamyl, carboxyl, carbalkoxy, —(CH2)n—CO2H, chloro, cyano, cyanoguanidinyl, fluoro, guanidino, hydrazide, hydrazino, hydrazido, hydroxy, hydroxyamino, iodo, nitro, phosphono, —SO3H, thioacetal, thiocarbonyl, and C1-C6 carbonyl;
where n is from 1 to 8;
(c) is the group -(L1)-R81;
where, -(L1)- is a divalent linking group having the formula;
45
where,
R84 and R85 are each independently selected from hydrogen, C1-C10 alkyl, carboxyl, carbalkoxy, or halo;
p is 1 to 5,
Z is a bond, —(CH2)—, —O—, —N(C1-C10 alkyl)-, —NH—, or —S—;
and where R81 is a group selected from (a) or (b);
R12 is hydrogen, halo, C1-C3 alkyl, C3-C4 cycloalkyl, C3-C4 cycloalkenyl, —O—(C1-C2 alkyl), or —S—(C1-C2 alkyl);
R14 is hydrogen or a group, -(La)-(acidic group) wherein -(La)- is represented by the formula;
46
where
Q is selected from the group —(CH2)—, —O—, —NH—, and —S—, and R84 and R85 are each independently selected from hydrogen, C1-C10 alkyl, aryl, C1-C10 alkaryl, C1-C10 aralkyl, and halo;
R15 is hydrogen or a group, -(La′)-(acidic group) wherein -(La′)- is represented by the formula;
47
where
r is a number from 1 to 7, s is 0 or 1, and Q is selected from the group —(CH2)—, —O—, —NH—, and —S—, and R84′ and R85′ are each independently selected from hydrogen, C1-C10 alkyl, aryl, C1-C10 alkaryl, C1-C10 aralkyl, carboxy, carbalkoxy, and halo;
provided that at least one of R14 or R15 must be the group, -(La)-(acidic group) or -(La′)-(acidic group);
R16 Is hydrogen, carboxyl or ester thereof;
R17 is selected from hydrogen, non-interfering substituents, selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C7-C12 aralkyl, C7-C12 alkaryl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, phenyl, tolyl, xylyl, biphenyl, C1-C6 alkoxy, C2-C6 alkenyloxy, C2-C6 alkynyloxy, C2-C12 alkoxyalkyl, C2-C12 alkoxyalkyloxy, C2-C12 alkylcarbonyl, C2-C12 alkylcarbonylamino, C2-C12 alkoxyamino, C2-C12 alkoxyaminocarbonyl, C2-C12 alkylamino, C1-C6 alkylthio, C2-C12 alkylthiocarbonyl, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C2-C6 haloalkoxy, C1-C6 haloalkylsulfonyl, C2-C6 haloalkyl, C1-C6 hydroxyalkyl, —C(O)O(C1-C6 alkyl), —(CH2)n—O—(C1-C6 alkyl), benzyloxy, phenoxy, phenylthio, —CHO, amino, amidino, bromo, carbamyl, carboxyl, carbalkoxy, —(CH2)n—CO2H, chloro, cyano, cyanoguanidinyl, fluoro, guanidino, hydrazide, hydrazino, hydrazido, hydroxy, hydroxyamino, iodo, nitro, phosphono, —SO3H, thioacetal, thiocarbonyl, and C1-C6 carbonyl;
where n is from 1 to 8.

33 more elements

where the compound is an N-heterocyclic glyoxylamide compound or a pharmaceutically acceptable salt, solvate, or prodrug derivative thereof selected from the group consisting of compounds (A) through (NN):
(A) [[3-(2-Amino-1,2-dioxoethyl)-2-methyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid,
(B) dl-2-[[3-(2-Amino-1,2-dioxoethyl)-2-methyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]propanoic acid,
(C) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-2-ylmethyl)-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(D) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-3-ylmethyl)-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(E) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-4-ylmethyl)-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(F) [[3-(2-Amino-1,2-dioxoethyl)-1-[(2,6-dichlorophenyl)methyl]-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(G) [[3-(2-Amino-1,2-dioxoethyl)-1-[(4-fluorophenyl)methyl]-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(H) [[3-(2-Amino-1,2-dioxoethyl)-2-methyl-1-[(1-naphthalenyl)methyl]-1H-indol-4-yl]oxy]acetic acid,
(I) [[3-(2-Amino-1,2-dioxoethyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid,
(I′) [[3-(2-Amino-1,2-dioxoethyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid methyl ester
(J) [[3-(2-Amino-1,2-dioxoethyl)-1-[(3-chlorophenyl)methyl]-2-ethyl-1H-indol-4-yl]oxy]acetic acid,
(K) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-2-ylmethyl)-2-ethyl-1H-indol-4-yl]oxy]acetic acid,
(L) [[3-(2-amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-2-ylmethyl)-2-propyl-1H-indol-4-yl]oxy]acetic acid,
(M) [[3-(2-Amino-1,2-dioxoethyl)-2-cyclopropyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid,
(N) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-2-ylmethyl)-2-cyclopropyl-1H-indol-4-yl]oxy]acetic acid,
(O) 4-[[3-(2-Amino-1,2-dioxoethyl)-2-ethyl-1-(phenylmethyl)-1H-indol-5-yl]oxy]butanoic acid,
(P) mixtures of (A) through (O),
(Q) (8-(Carbomethoxymethyloxy)-2-ethyl-3-(o-phenylbenzyl)indolizin-1-yl)glyoxylamide,
(R) (3-Benzyl-8-(carbethoxymethyloxy)-2-ethylindolizin-1-yl)glyoxylamide,
(S) (8-(Carbethoxymethyloxy)-2-ethyl-3-(o-phenylbenzyl)indolizin-1-yl)glyoxylamide,
(T) (3-Benzyl-8-(carbethoxymethyloxy)-2-methylindolizin-1-yl)glyoxylamide,
(U) (8-(Carbethoxymethyloxy)-3-(m-chlorobenzyl)-2-ethylindolizin-1-yl)glyoxylamide,
(V) (8-Carbethoxymethyloxy-2-ethyl-3-(1-naphthylmethyl)indolizin-1-yl)glyoxylamide,
(W) (3-Benzyl-8-(t-butoxycarbonylmethyloxy)-2-ethylindolizin-1-yl)glyoxylamide,
(X) (8-(Carbmethoxymethyloxy)-2-ethyl-3-(m-trifluoromethylbenzyl)indolizin-1-yl)glyoxylamide,
(Y) (8-(Carbmethoxymethyloxy)-2-cyclopropyl-3-(o-phenylbenzyl)indolizin-1-yl)glyoxylamide,
(Z) (3-Benzyl-8-(carboxymethyloxy)-2-ethylindolizin-1-yl)glyoxylamide,
(AA) (8-(Carboxymethyloxy)-2-ethyl-3-(o-phenylbenzyl)indolizin-1-yl)glyoxylamide,
(AA′) (8-Carbomethoxymethyloxy)-2-ethyl-3-(o-phenylbenzyl)indolizin-1-yl)glyoxylamide,
(BB) (3-Benzyl-8-(carboxymethyloxy)-2-methylindolizin-1-yl)glyoxylamide,
(CC) (8-(Carboxymethyloxy)-3-(m-chlorobenzyl)-2-ethylindolizin-1-yl)glyoxylamide,
(DD) (8-(Carboxymethyloxy)-2-ethyl-3-(m-trifluoromethylbenzyl)indolizin-1-yl)glyoxylamide,
(EE) (8-Carboxymethyloxy-2-ethyl-3-(1-naphthylmethyl)indolizin-1-yl)glyoxylamide,
(FF) (8-(Carboxymethyloxy)-2-cyclopropyl-3-(o-phenylbenzyl)indolizin-1-yl) glyoxylamide,
(GG) mixtures of (Q) through (FF),
(HH) [[3-(2-Amino-1,2-dioxoethyl)-6-carboxyl-2-ethyl-1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(II) [[3-(2-Amino-1,2-dioxoethyl)-6-methoxycarbonyl-2-ethyl-1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(JJ) [[3-(2-Amino-1,2-dioxoethyl)-6-ethoxycarbonyl-2-ethyl-1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(KK) [[3-(2-Amino-1,2-dioxoethyl)-6-n-propoxycarbonyl-2-ethyl-1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(LL) [[3-(2-Amino-1,2-dioxoethyl)-6-i-propoxycarbonyl-2-ethyl-1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(MM) [[3-(2-Amino-1,2-dioxoethyl)-6-cyclopropyloxycarbonyl-2-ethyl-1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(NN) mixtures of (HH) through (MM).

40 more elements

A composition for treatment of disorders associated with apoptosis;

which comprises an N-heterocyclic glyoxylamide compound represented by the formula (I) or a pharmaceutically acceptable salt, solvate, or prodrug derivative thereof:
52
E and F are differently C or N;
--- is presence or absence of a double bond;
each X is independently oxygen or sulfur;
R11 is selected from groups (a), (b) and (c) where;
(a) is C7-C20 alkyl, C7-C20 alkenyl, C7-C20 alkynyl;
or carbocyclic radical selected from the group cycloalkyl, cycloalkenyl, phenyl, naphthyl, norbornanyl, bicycloheptadienyl, tolyl, xylyl, indenyl, stilbenyl, terphenylyl, diphenylethylenyl, phenyl-cyclohexenyl, acenaphthylenyl, and anthryl, biphenyl, bibenzylyl and related bibenzylyl homologues represented by the formula (bb),
53
where
n is a number from 1 to 8;
or
(b) is a member of (a) substituted with one or more independently selected non-interfering substituents selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C7-C12 aralkyl, C7-C12 alkaryl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, phenyl, tolyl, xylyl, biphenyl, C1-C6 alkoxy, C2-C6 alkenyloxy, C2-C6 alkynyloxy, C2-C12 alkoxyalkyl, C2-C12 alkoxyalkyloxy, C2-C12 alkylcarbonyl, C2-C12 alkylcarbonylamino, C2-C12 alkoxyamino, C2-C12 alkoxyaminocarbonyl, C1-C12 alkylamino, C1-C6 alkylthio, C2-C12 alkylthiocarbonyl, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C2-C6 haloalkoxy, C1-C6 haloalkylsulfonyl, C2-C6 haloalkyl, C1-C6 hydroxyalkyl, —C(O)O(C1-C6 alkyl), —(CH2)n—O—(C1-C6 alkyl), benzyloxy, phenoxy, phenylthio, —CHO, amino, amidino, bromo, carbamyl, carboxyl, carbalkoxy, —(CH2)n—CO2H, chloro, cyano, cyanoguanidinyl, fluoro, guanidino, hydrazide, hydrazino, hydrazido, hydroxy, hydroxyamino, iodo, nitro, phosphono, —SO3H, thioacetal, thiocarbonyl, and C1-C6 carbonyl;
where n is from 1 to 8;
(c) is the group -(L1)-R81;
where, -(L1)- is a divalent linking group having the formula;
54
where,
R84 and R85 are each independently selected from hydrogen, C1-C10 alkyl, carboxyl, carbalkoxy, or halo;
p is 1 to 5,
Z is a bond, —(CH2)—, —O—, —N(C1-C10 alkyl)-, —NH—, or —S—;
and where R81 is a group selected from (a) or (b);
R12 is hydrogen, halo, C1-C3 alkyl, C3-C4 cycloalkyl, C3-C4 cycloalkenyl, —O—(C1-C2 alkyl), or —S—(C1-C2 alkyl);
R14 is hydrogen or a group, -(La)-(acidic group) wherein -(La)- is represented by the formula;
55
where
Q is selected from the group —(CH2)—, —O—, —NH—, and —S—, and R84 and R85 are each independently selected from hydrogen, C1-C10 alkyl, aryl, C1-C10 alkaryl, C1-C10 aralkyl, and halo;
R15 is hydrogen or a group, -(La′)-(acidic group) wherein -(La′)- is represented by the formula;
56
where
r is a number from 1 to 7, s is 0 or 1, and Q is selected from the group —(CH2)—, —O—, —NH—, and —S—, and R84′ and R85′ are each independently selected from hydrogen, C1-C10 alkyl, aryl, C1-C10 alkaryl, C1-C10 aralkyl, carboxy, carbalkoxy, and halo;
provided that at least one of R14 or R15 must be the group, -(La)-(acidic group) or -(La′)-(acidic group);
R16 is hydrogen, carboxyl or ester thereof;
R17 is selected from hydrogen, non-interfering substituents, selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C7-C12 aralkyl, C7-C12 alkaryl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, phenyl, tolyl, xylyl, biphenyl, C1-C6 alkoxy, C2-C6 alkenyloxy, C2-C6 alkynyloxy, C2-C12 alkoxyalkyl, C2-C12 alkoxyalkyloxy, C2-C12 alkylcarbonyl, C2-C12 alkylcarbonylamino, C2-C12 alkoxyamino, C2-C12 alkoxyaminocarbonyl, C2-C12 alkylamino, C1-C6 alkylthio, C2-C12 alkylthiocarbonyl, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C2-C6 haloalkoxy, C1-C6 haloalkylsulfonyl, C2-C6 haloalkyl, C1-C6 hydroxyalkyl, —C(O)O(C1-C6 alkyl), —(CH2)n—O—(C1-C6 alkyl), benzyloxy, phenoxy, phenylthio, —CHO, amino, amidino, bromo, carbamyl, carboxyl, carbalkoxy, —(CH2)n—CO2H, chloro, cyano, cyanoguanidinyl, fluoro, guanidino, hydrazide, hydrazino, hydrazido, hydroxy, hydroxyamino, iodo, nitro, phosphono, —SO3H, thioacetal, thiocarbonyl, and C1-C6 carbonyl;
where n is from 1 to 8.

32 more elements

A composition for treatment of disorders associated with apoptosis;

which comprises an N-heterocyclic glyoxylamide compound or a pharmaceutically acceptable salt, solvate, or prodrug derivative thereof selected from the group consisting of compounds (A) through (NN):
(A) [[3-(2-Amino-1,2-dioxoethyl)-2-methyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid,
(B) dl-2-[[3-(2-Amino-1,2-dioxoethyl)-2-methyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]propanoic acid,
(C) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-2-ylmethyl)-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(D) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-3-ylmethyl)-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(E) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-4-ylmethyl)-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(F) [[3-(2-Amino-1,2-dioxoethyl)-1-[(2,6-dichlorophenyl)methyl]-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(G) [[3-(2-Amino-1,2-dioxoethyl)-1-[(4-fluorophenyl)methyl]-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(H) [[3-(2-Amino-1,2-dioxoethyl)-2-methyl-1-[(1-naphthalenyl)methyl]-1H-indol-4-yl]oxy]acetic acid,
(I) [[3-(2-Amino-1,2-dioxoethyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid,
(I′) [[3-(2-Amino-1,2-dioxoethyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid methyl ester
(J) [[3-(2-Amino-1,2-dioxoethyl)-1-[(3-chlorophenyl)methyl]-2-ethyl-1H-indol-4-yl]oxy]acetic acid,
(K) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-2-ylmethyl)-2-ethyl-1H-indol-4-yl]oxy]acetic acid,
(L) [[3-(2-amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-2-ylmethyl)-2-propyl-1H-indol-4-yl]oxy]acetic acid,
(M) [[3-(2-Amino-1,2-dioxoethyl)-2-cyclopropyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid,
(N) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-2-ylmethyl)-2-cyclopropyl-1H-indol-4-yl]oxy]acetic acid,
(O) 4-[[3-(2-Amino-1,2-dioxoethyl)-2-ethyl-1-(phenylmethyl)-1H-indol-5-yl]oxy]butanoic acid,
(P) mixtures of (A) through (O),
(Q) (8-(Carbomethoxymethyloxy)-2-ethyl-3-(o-phenylbenzyl)indolizin-1-yl)glyoxylamide,
(R) (3-Benzyl-8-(carbethoxymethyloxy)-2-ethylindolizin-1-yl)glyoxylamide,
(S) (8-(Carbethoxymethyloxy)-2-ethyl-3-(o-phenylbenzyl)indolizin-1-yl)glyoxylamide,
(T) (3-Benzyl-8-(carbethoxymethyloxy)-2-methylindolizin-1-yl)glyoxylamide,
(U) (8-(Carbethoxymethyloxy)-3-(m-chlorobenzyl)-2-ethylindolizin-1-yl)glyoxylamide,
(V) (8-Carbethoxymethyloxy-2-ethyl-3-(1-naphthylmethyl)indolizin-1-yl)glyoxylamide,
(W) (3-Benzyl-8-(t-butoxycarbonylmethyloxy)-2-ethylindolizin-1-yl)glyoxylamide,
(X) (8-(Carbmethoxymethyloxy)-2-ethyl-3-(m-trifluoromethylbenzyl)indolizin-1-yl)glyoxylamide,
(Y) (8-(Carbmethoxymethyloxy)-2-cyclopropyl-3-(o-phenylbenzyl)indolizin-1-yl)glyoxylamide,
(Z) (3-Benzyl-8-(carboxymethyloxy)-2-ethylindolizin-1-yl)glyoxylamide,
(AA) (8-(Carboxymethyloxy)-2-ethyl-3-(o-phenylbenzyl)indolizin-1-yl)glyoxylamide,
(AA′) (8-Carbomethoxymethyloxy)-2-ethyl-3-(o-phenylbenzyl)indolizin-1-yl)glyoxylamide,
(BB) (3-Benzyl-8-(carboxymethyloxy)-2-methylindolizin-1-yl)glyoxylamide,
(CC) (8-(Carboxymethyloxy)-3-(m-chlorobenzyl)-2-ethylindolizin-1-yl)glyoxylamide,
(DD) (8-(Carboxymethyloxy)-2-ethyl-3-(m-trifluoromethylbenzyl)indolizin-1-yl)glyoxylamide,
(EE) (8-Carboxymethyloxy-2-ethyl-3-(1-naphthylmethyl)indolizin-1-yl)glyoxylamide,
(FF) (8-(Carboxymethyloxy)-2-cyclopropyl-3-(o-phenylbenzyl)indolizin-1-yl) glyoxylamide,
(GG) mixtures of (Q) through (FF),
(HH) [[3-(2-Amino-1,2-dioxoethyl)-6-carboxyl-2-ethyl-1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(II) [[3-(2-Amino-1,2-dioxoethyl)-6-methoxycarbonyl-2-ethyl-1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(JJ) [[3-(2-Amino-1,2-dioxoethyl)-6-ethoxycarbonyl-2-ethyl-1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(KK) [[3-(2-Amino-1,2-dioxoethyl)-6-n-propoxycarbonyl-2-ethyl 1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(LL) [[3-(2-Amino-1,2-dioxoethyl)-6-i-propoxycarbonyl-2-ethyl-1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(MM) [[3-(2-Amino-1,2-dioxoethyl)-6-cyclopropyloxycarbonyl-2-ethyl-1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(NN) mixtures of (HH) through (MM).

40 more elements

Dependencies are inferred from the claim text.

Facts

Application

10/219,931Filed 16 Aug 2002

Priority

10 Nov 1998

Published

7 Aug 2003

Term ends

Not estimatedThe source records don’t support an estimate.

Classification3 codes

A61K 31/437
Ortho- or peri-condensed with heterocyclic ring systems: the heterocyclic ring system containing a five-membered ring having nitrogen as a ring…
A61K 31/4045
Indoles, e.g. pindolol: indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
A61K
Medicines and medical preparations

Abstract

A method or composition is disclosed for the treatment of disorders associated with apoptosis using N-heterocyclic glyoxylamide compounds.

Claims29

Dependent claims

34
wherein;
E and F are differently C or N;
--- is presence or absence of a double bond;
each X is independently oxygen or sulfur;
R11 is selected from groups (a), (b) and (c) where;
(a) is C7-C20 alkyl, C7-C20 alkenyl, C7-C20 alkynyl;
or carbocyclic radical selected from the group cycloalkyl, cycloalkenyl, phenyl, naphthyl, norbornanyl, bicycloheptadienyl, tolyl, xylyl, indenyl, stilbenyl, terphenylyl, diphenylethylenyl, phenyl-cyclohexenyl, acenaphthylenyl, and anthryl, biphenyl, bibenzylyl and related bibenzylyl homologues represented by the formula (bb),
35
where
n is a number from 1 to 8;
or
(b) is a member of (a) substituted with one or more independently selected non-interfering substituents selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C7-C12 aralkyl, C7-C12 alkaryl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, phenyl, tolyl, xylyl, biphenyl, C1-C6 alkoxy, C2-C6 alkenyloxy, C2-C6 alkynyloxy, C2-C12 alkoxyalkyl, C2-C12 alkoxyalkyloxy, C2-C12 alkylcarbonyl, C2-C12 alkylcarbonylamino, C2-C12 alkoxyamino, C2-C12 alkoxyaminocarbonyl, C1-C12 alkylamino, C1-C6 alkylthio, C2-C12 alkylthiocarbonyl, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C2-C6 haloalkoxy, C1-C6 haloalkylsulfonyl, C2-C6 haloalkyl, C1-C6 hydroxyalkyl, —C(O)O(C1-C6 alkyl), —(CH2)n—O—(C1-C6 alkyl), benzyloxy, phenoxy, phenylthio, —CHO, amino, amidino, bromo, carbamyl, carboxyl, carbalkoxy, —(CH2)n—CO2H, chloro, cyano, cyanoguanidinyl, fluoro, guanidino, hydrazide, hydrazino, hydrazido, hydroxy, hydroxyamino, iodo, nitro, phosphono, —SO3H, thioacetal, thiocarbonyl, and C1-C6 carbonyl;
where n is from 1 to 8;
(c) is the group -(L1)-R81;
where, -(L1)- is a divalent linking group having the formula;
36
where,
R84 and R85 are each independently selected from hydrogen, C1-C10 alkyl, carboxyl, carbalkoxy, or halo;
p is 1 to 5,
Z is a bond, —(CH2)—, —O—, —N(C1-C10 alkyl)-, —NH—, or —S—;
and where R81 is a group selected from (a) or (b);
R12 is hydrogen, halo, C1-C3 alkyl, C3-C4 cycloalkyl, C3-C4 cycloalkenyl, —O—(C1-C2 alkyl), or —S—(C1-C2 alkyl);
R14 is hydrogen or a group, -(La)-(acidic group) wherein -(La)- is represented by the formula;
37
where
Q is selected from the group —(CH2)—, —O—, —NH—, and —S—, and R84 and R85 are each independently selected from hydrogen, C1-C10 alkyl, aryl, C1-C10 alkaryl, C1-C10 aralkyl, and halo;
R15 is hydrogen or a group, -(La′)-(acidic group) wherein -(La′)- is represented by the formula;
38
where
r is a number from 1 to 7, s is 0 or 1, and Q is selected from the group —(CH2)—, —O—, —NH—, and —S—, and R84′ and R85′ are each independently selected from hydrogen, C1-C10 alkyl, aryl, C1-C10 alkaryl, C1-C10 aralkyl, carboxy, carbalkoxy, and halo;
provided that at least one of R14 or R15 must be the group, -(La)-(acidic group) or -(La′)-(acidic group);
R16 is hydrogen, carboxyl or ester thereof;
R17 is selected from hydrogen, non-interfering substituents, selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C7-C12 aralkyl, C7-C12 alkaryl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, phenyl, tolyl, xylyl, biphenyl, C1-C6 alkoxy, C2-C6 alkenyloxy, C2-C6 alkynyloxy, C2-C12 alkoxyalkyl, C2-C12 alkoxyalkyloxy, C2-C12 alkylcarbonyl, C2-C12 alkylcarbonylamino, C2-C12 alkoxyamino, C2-C12 alkoxyaminocarbonyl, C2-C12 alkylamino, C1-C6 alkylthio, C2-C12 alkylthiocarbonyl, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C2-C6 haloalkoxy, C1-C6 haloalkylsulfonyl, C2-C6 haloalkyl, C1-C6 hydroxyalkyl, —C(O)O(C1-C6 alkyl), —(CH2)n—O—(C1-C6 alkyl), benzyloxy, phenoxy, phenylthio, —CHO, amino, amidino, bromo, carbamyl, carboxyl, carbalkoxy, —(CH2)n—CO2H, chloro, cyano, cyanoguanidinyl, fluoro, guanidino, hydrazide, hydrazino, hydrazido, hydroxy, hydroxyamino, iodo, nitro, phosphono, —SO3H, thioacetal, thiocarbonyl, and C1-C6 carbonyl;
where n is from 1 to 8.

32 more elements

A method of treatment of a mammal currently afflicted with disorders associated with apoptosis or previously afflicted with disorders associated with apoptosis, said method comprising administering to said mammal in need of such treatment a therapeutically effective amount of an N-heterocyclic glyoxylamide compound or a pharmaceutically acceptable salt, solvate, or a prodrug derivative thereof selected from the group consisting of compounds (A) through (NN):

(A) [[3-(2-Amino-1,2-dioxoethyl)-2-methyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid,
(B) dl-2-[[3-(2-Amino-1,2-dioxoethyl)-2-methyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]propanoic acid,
(C) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-2-ylmethyl)-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(D) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-3-ylmethyl)-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(E) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-4-ylmethyl)-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(F) [[3-(2-Amino-1,2-dioxoethyl)-1-[(2,6-dichlorophenyl)methyl]-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(G) [[3-(2-Amino-1,2-dioxoethyl)-1-[(4-fluorophenyl)methyl]-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(H) [[3-(2-Amino-1,2-dioxoethyl)-2-methyl-1-[(1-naphthalenyl)methyl]-1H-indol-4-yl]oxy]acetic acid,
(I) [[3-(2-Amino-1,2-dioxoethyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid,
(I′) [[3-(2-Amino-1,2-dioxoethyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid methyl ester
(J) [[3-(2-Amino-1,2-dioxoethyl)-1-[(3-chlorophenyl)methyl]-2-ethyl-1H-indol-4-yl]oxy]acetic acid,
(K) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-2-ylmethyl)-2-ethyl-1H-indol-4-yl]oxy]acetic acid,
(L) [[3-(2-amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-2-ylmethyl)-2-propyl-1H-indol-4-yl]oxy]acetic acid,
(M) [[3-(2-Amino-1,2-dioxoethyl)-2-cyclopropyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid,
(N) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-2-ylmethyl)-2-cyclopropyl-1H-indol-4-yl]oxy]acetic acid,
(O) 4-[[3-(2-Amino-1,2-dioxoethyl)-2-ethyl-1-(phenylmethyl)-1H-indol-5-yl]oxy]butanoic acid,
(P) mixtures of (A) through (O),
(Q) (8-(Carbomethoxymethyloxy)-2-ethyl-3-(o-phenylbenzyl)indolizin-1-yl)glyoxylamide,
(R) (3-Benzyl-8-(carbethoxymethyloxy)-2-ethylindolizin-1-yl)glyoxylamide,
(S) (8-(Carbethoxymethyloxy)-2-ethyl-3-(o-phenylbenzyl)indolizin-1-yl)glyoxylamide,
(T) (3-Benzyl-8-(carbethoxymethyloxy)-2-methylindolizin-1-yl)glyoxylamide,
(U) (8-(Carbethoxymethyloxy)-3-(m-chlorobenzyl)-2-ethylindolizin-1-yl)glyoxylamide,
(V) (8-Carbethoxymethyloxy-2-ethyl-3-(1-naphthylmethyl)indolizin-1-yl)glyoxylamide,
(W) (3-Benzyl-8-(t-butoxycarbonylmethyloxy)-2-ethylindolizin-1-yl)glyoxylamide,
(X) (8-(Carbmethoxymethyloxy)-2-ethyl-3-(m-trifluoromethylbenzyl)indolizin-1-yl)glyoxylamide,
(Y) (8-(Carbmethoxymethyloxy)-2-cyclopropyl-3-(o-phenylbenzyl)indolizin-1-yl)glyoxylamide,
(Z) (3-Benzyl-8-(carboxymethyloxy)-2-ethylindolizin-1-yl)glyoxylamide,
(AA) (8-(Carboxymethyloxy)-2-ethyl-3-(o-phenylbenzyl)indolizin-1-yl)glyoxylamide,
(AA′) (8-Carbomethoxymethyloxy)-2-ethyl-3-(o-phenylbenzyl)indolizin-1-yl)glyoxylamide,
(BB) (3-Benzyl-8-(carboxymethyloxy)-2-methylindolizin-1-yl)glyoxylamide,
(CC) (8-(Carboxymethyloxy)-3-(m-chlorobenzyl)-2-ethylindolizin-1-yl)glyoxylamide,
(DD) (8-(Carboxymethyloxy)-2-ethyl-3-(m-trifluoromethylbenzyl)indolizin-1-yl)glyoxylamide,
(EE) (8-Carboxymethyloxy-2-ethyl-3-(1-naphthylmethyl)indolizin-1-yl)glyoxylamide,
(FF) (8-(Carboxymethyloxy)-2-cyclopropyl-3-(o-phenylbenzyl)indolizin-1-yl) glyoxylamide,
(GG) mixtures of (Q) through (FF),
(HH) [[3-(2-Amino-1,2-dioxoethyl)-6-carboxyl-2-ethyl-1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(II) [[3-(2-Amino-1,2-dioxoethyl)-6-methoxycarbonyl-2-ethyl-1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(JJ) [[3-(2-Amino-1,2-dioxoethyl)-6-ethoxycarbonyl-2-ethyl-1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(KK) [[3-(2-Amino-1,2-dioxoethyl)-6-n-propoxycarbonyl-2-ethyl 1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(LL) [[3-(2-Amino-1,2-dioxoethyl)-6-i-propoxycarbonyl-2-ethyl-1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(MM) [[3-(2-Amino-1,2-dioxoethyl)-6-cyclopropyloxycarbonyl-2-ethyl-1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(NN) mixtures of (HH) through (MM).

39 more elements

where the compound is represented by the formula (I) or a pharmaceutically acceptable salt, solvate, or prodrug derivative thereof:
43
wherein
E and F are differently C or N;
--- is presence or absence of a double bond;
each X is independently oxygen or sulfur;
R11 is selected from groups (a), (b) and (c) where;
(a) is C7-C20 alkyl, C7-C20 alkenyl, C7-C20 alkynyl;
or carbocyclic radical selected from the group cycloalkyl, cycloalkenyl, phenyl, naphthyl, norbornanyl, bicycloheptadienyl, tolyl, xylyl, indenyl, stilbenyl, terphenylyl, diphenylethylenyl, phenyl-cyclohexenyl, acenaphthylenyl, and anthryl, biphenyl, bibenzylyl and related bibenzylyl homologues represented by the formula (bb),
44
where
n is a number from 1 to 8;
or
(b) is a member of (a) substituted with one or more independently selected non-interfering substituents selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C7-C12 aralkyl, C7-C12 alkaryl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, phenyl, tolyl, xylyl, biphenyl, C1-C6 alkoxy, C2-C6 alkenyloxy, C2-C6 alkynyloxy, C2-C12 alkoxyalkyl, C2-C12 alkoxyalkyloxy, C2-C12 alkylcarbonyl, C2-C12 alkylcarbonylamino, C2-C12 alkoxyamino, C2-C12 alkoxyaminocarbonyl, C1-C12 alkylamino, C1-C6 alkylthio, C2-C12 alkylthiocarbonyl, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C2-C6 haloalkoxy, C1-C6 haloalkylsulfonyl, C2-C6 haloalkyl, C1-C6 hydroxyalkyl, —C(O)O(C1-C6 alkyl), —(CH2)n—O—(C1-C6 alkyl), benzyloxy, phenoxy, phenylthio, —CHO, amino, amidino, bromo, carbamyl, carboxyl, carbalkoxy, —(CH2)n—CO2H, chloro, cyano, cyanoguanidinyl, fluoro, guanidino, hydrazide, hydrazino, hydrazido, hydroxy, hydroxyamino, iodo, nitro, phosphono, —SO3H, thioacetal, thiocarbonyl, and C1-C6 carbonyl;
where n is from 1 to 8;
(c) is the group -(L1)-R81;
where, -(L1)- is a divalent linking group having the formula;
45
where,
R84 and R85 are each independently selected from hydrogen, C1-C10 alkyl, carboxyl, carbalkoxy, or halo;
p is 1 to 5,
Z is a bond, —(CH2)—, —O—, —N(C1-C10 alkyl)-, —NH—, or —S—;
and where R81 is a group selected from (a) or (b);
R12 is hydrogen, halo, C1-C3 alkyl, C3-C4 cycloalkyl, C3-C4 cycloalkenyl, —O—(C1-C2 alkyl), or —S—(C1-C2 alkyl);
R14 is hydrogen or a group, -(La)-(acidic group) wherein -(La)- is represented by the formula;
46
where
Q is selected from the group —(CH2)—, —O—, —NH—, and —S—, and R84 and R85 are each independently selected from hydrogen, C1-C10 alkyl, aryl, C1-C10 alkaryl, C1-C10 aralkyl, and halo;
R15 is hydrogen or a group, -(La′)-(acidic group) wherein -(La′)- is represented by the formula;
47
where
r is a number from 1 to 7, s is 0 or 1, and Q is selected from the group —(CH2)—, —O—, —NH—, and —S—, and R84′ and R85′ are each independently selected from hydrogen, C1-C10 alkyl, aryl, C1-C10 alkaryl, C1-C10 aralkyl, carboxy, carbalkoxy, and halo;
provided that at least one of R14 or R15 must be the group, -(La)-(acidic group) or -(La′)-(acidic group);
R16 Is hydrogen, carboxyl or ester thereof;
R17 is selected from hydrogen, non-interfering substituents, selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C7-C12 aralkyl, C7-C12 alkaryl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, phenyl, tolyl, xylyl, biphenyl, C1-C6 alkoxy, C2-C6 alkenyloxy, C2-C6 alkynyloxy, C2-C12 alkoxyalkyl, C2-C12 alkoxyalkyloxy, C2-C12 alkylcarbonyl, C2-C12 alkylcarbonylamino, C2-C12 alkoxyamino, C2-C12 alkoxyaminocarbonyl, C2-C12 alkylamino, C1-C6 alkylthio, C2-C12 alkylthiocarbonyl, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C2-C6 haloalkoxy, C1-C6 haloalkylsulfonyl, C2-C6 haloalkyl, C1-C6 hydroxyalkyl, —C(O)O(C1-C6 alkyl), —(CH2)n—O—(C1-C6 alkyl), benzyloxy, phenoxy, phenylthio, —CHO, amino, amidino, bromo, carbamyl, carboxyl, carbalkoxy, —(CH2)n—CO2H, chloro, cyano, cyanoguanidinyl, fluoro, guanidino, hydrazide, hydrazino, hydrazido, hydroxy, hydroxyamino, iodo, nitro, phosphono, —SO3H, thioacetal, thiocarbonyl, and C1-C6 carbonyl;
where n is from 1 to 8.

33 more elements

where the compound is an N-heterocyclic glyoxylamide compound or a pharmaceutically acceptable salt, solvate, or prodrug derivative thereof selected from the group consisting of compounds (A) through (NN):
(A) [[3-(2-Amino-1,2-dioxoethyl)-2-methyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid,
(B) dl-2-[[3-(2-Amino-1,2-dioxoethyl)-2-methyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]propanoic acid,
(C) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-2-ylmethyl)-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(D) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-3-ylmethyl)-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(E) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-4-ylmethyl)-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(F) [[3-(2-Amino-1,2-dioxoethyl)-1-[(2,6-dichlorophenyl)methyl]-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(G) [[3-(2-Amino-1,2-dioxoethyl)-1-[(4-fluorophenyl)methyl]-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(H) [[3-(2-Amino-1,2-dioxoethyl)-2-methyl-1-[(1-naphthalenyl)methyl]-1H-indol-4-yl]oxy]acetic acid,
(I) [[3-(2-Amino-1,2-dioxoethyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid,
(I′) [[3-(2-Amino-1,2-dioxoethyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid methyl ester
(J) [[3-(2-Amino-1,2-dioxoethyl)-1-[(3-chlorophenyl)methyl]-2-ethyl-1H-indol-4-yl]oxy]acetic acid,
(K) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-2-ylmethyl)-2-ethyl-1H-indol-4-yl]oxy]acetic acid,
(L) [[3-(2-amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-2-ylmethyl)-2-propyl-1H-indol-4-yl]oxy]acetic acid,
(M) [[3-(2-Amino-1,2-dioxoethyl)-2-cyclopropyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid,
(N) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-2-ylmethyl)-2-cyclopropyl-1H-indol-4-yl]oxy]acetic acid,
(O) 4-[[3-(2-Amino-1,2-dioxoethyl)-2-ethyl-1-(phenylmethyl)-1H-indol-5-yl]oxy]butanoic acid,
(P) mixtures of (A) through (O),
(Q) (8-(Carbomethoxymethyloxy)-2-ethyl-3-(o-phenylbenzyl)indolizin-1-yl)glyoxylamide,
(R) (3-Benzyl-8-(carbethoxymethyloxy)-2-ethylindolizin-1-yl)glyoxylamide,
(S) (8-(Carbethoxymethyloxy)-2-ethyl-3-(o-phenylbenzyl)indolizin-1-yl)glyoxylamide,
(T) (3-Benzyl-8-(carbethoxymethyloxy)-2-methylindolizin-1-yl)glyoxylamide,
(U) (8-(Carbethoxymethyloxy)-3-(m-chlorobenzyl)-2-ethylindolizin-1-yl)glyoxylamide,
(V) (8-Carbethoxymethyloxy-2-ethyl-3-(1-naphthylmethyl)indolizin-1-yl)glyoxylamide,
(W) (3-Benzyl-8-(t-butoxycarbonylmethyloxy)-2-ethylindolizin-1-yl)glyoxylamide,
(X) (8-(Carbmethoxymethyloxy)-2-ethyl-3-(m-trifluoromethylbenzyl)indolizin-1-yl)glyoxylamide,
(Y) (8-(Carbmethoxymethyloxy)-2-cyclopropyl-3-(o-phenylbenzyl)indolizin-1-yl)glyoxylamide,
(Z) (3-Benzyl-8-(carboxymethyloxy)-2-ethylindolizin-1-yl)glyoxylamide,
(AA) (8-(Carboxymethyloxy)-2-ethyl-3-(o-phenylbenzyl)indolizin-1-yl)glyoxylamide,
(AA′) (8-Carbomethoxymethyloxy)-2-ethyl-3-(o-phenylbenzyl)indolizin-1-yl)glyoxylamide,
(BB) (3-Benzyl-8-(carboxymethyloxy)-2-methylindolizin-1-yl)glyoxylamide,
(CC) (8-(Carboxymethyloxy)-3-(m-chlorobenzyl)-2-ethylindolizin-1-yl)glyoxylamide,
(DD) (8-(Carboxymethyloxy)-2-ethyl-3-(m-trifluoromethylbenzyl)indolizin-1-yl)glyoxylamide,
(EE) (8-Carboxymethyloxy-2-ethyl-3-(1-naphthylmethyl)indolizin-1-yl)glyoxylamide,
(FF) (8-(Carboxymethyloxy)-2-cyclopropyl-3-(o-phenylbenzyl)indolizin-1-yl) glyoxylamide,
(GG) mixtures of (Q) through (FF),
(HH) [[3-(2-Amino-1,2-dioxoethyl)-6-carboxyl-2-ethyl-1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(II) [[3-(2-Amino-1,2-dioxoethyl)-6-methoxycarbonyl-2-ethyl-1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(JJ) [[3-(2-Amino-1,2-dioxoethyl)-6-ethoxycarbonyl-2-ethyl-1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(KK) [[3-(2-Amino-1,2-dioxoethyl)-6-n-propoxycarbonyl-2-ethyl-1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(LL) [[3-(2-Amino-1,2-dioxoethyl)-6-i-propoxycarbonyl-2-ethyl-1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(MM) [[3-(2-Amino-1,2-dioxoethyl)-6-cyclopropyloxycarbonyl-2-ethyl-1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(NN) mixtures of (HH) through (MM).

40 more elements

A composition for treatment of disorders associated with apoptosis;

which comprises an N-heterocyclic glyoxylamide compound represented by the formula (I) or a pharmaceutically acceptable salt, solvate, or prodrug derivative thereof:
52
E and F are differently C or N;
--- is presence or absence of a double bond;
each X is independently oxygen or sulfur;
R11 is selected from groups (a), (b) and (c) where;
(a) is C7-C20 alkyl, C7-C20 alkenyl, C7-C20 alkynyl;
or carbocyclic radical selected from the group cycloalkyl, cycloalkenyl, phenyl, naphthyl, norbornanyl, bicycloheptadienyl, tolyl, xylyl, indenyl, stilbenyl, terphenylyl, diphenylethylenyl, phenyl-cyclohexenyl, acenaphthylenyl, and anthryl, biphenyl, bibenzylyl and related bibenzylyl homologues represented by the formula (bb),
53
where
n is a number from 1 to 8;
or
(b) is a member of (a) substituted with one or more independently selected non-interfering substituents selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C7-C12 aralkyl, C7-C12 alkaryl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, phenyl, tolyl, xylyl, biphenyl, C1-C6 alkoxy, C2-C6 alkenyloxy, C2-C6 alkynyloxy, C2-C12 alkoxyalkyl, C2-C12 alkoxyalkyloxy, C2-C12 alkylcarbonyl, C2-C12 alkylcarbonylamino, C2-C12 alkoxyamino, C2-C12 alkoxyaminocarbonyl, C1-C12 alkylamino, C1-C6 alkylthio, C2-C12 alkylthiocarbonyl, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C2-C6 haloalkoxy, C1-C6 haloalkylsulfonyl, C2-C6 haloalkyl, C1-C6 hydroxyalkyl, —C(O)O(C1-C6 alkyl), —(CH2)n—O—(C1-C6 alkyl), benzyloxy, phenoxy, phenylthio, —CHO, amino, amidino, bromo, carbamyl, carboxyl, carbalkoxy, —(CH2)n—CO2H, chloro, cyano, cyanoguanidinyl, fluoro, guanidino, hydrazide, hydrazino, hydrazido, hydroxy, hydroxyamino, iodo, nitro, phosphono, —SO3H, thioacetal, thiocarbonyl, and C1-C6 carbonyl;
where n is from 1 to 8;
(c) is the group -(L1)-R81;
where, -(L1)- is a divalent linking group having the formula;
54
where,
R84 and R85 are each independently selected from hydrogen, C1-C10 alkyl, carboxyl, carbalkoxy, or halo;
p is 1 to 5,
Z is a bond, —(CH2)—, —O—, —N(C1-C10 alkyl)-, —NH—, or —S—;
and where R81 is a group selected from (a) or (b);
R12 is hydrogen, halo, C1-C3 alkyl, C3-C4 cycloalkyl, C3-C4 cycloalkenyl, —O—(C1-C2 alkyl), or —S—(C1-C2 alkyl);
R14 is hydrogen or a group, -(La)-(acidic group) wherein -(La)- is represented by the formula;
55
where
Q is selected from the group —(CH2)—, —O—, —NH—, and —S—, and R84 and R85 are each independently selected from hydrogen, C1-C10 alkyl, aryl, C1-C10 alkaryl, C1-C10 aralkyl, and halo;
R15 is hydrogen or a group, -(La′)-(acidic group) wherein -(La′)- is represented by the formula;
56
where
r is a number from 1 to 7, s is 0 or 1, and Q is selected from the group —(CH2)—, —O—, —NH—, and —S—, and R84′ and R85′ are each independently selected from hydrogen, C1-C10 alkyl, aryl, C1-C10 alkaryl, C1-C10 aralkyl, carboxy, carbalkoxy, and halo;
provided that at least one of R14 or R15 must be the group, -(La)-(acidic group) or -(La′)-(acidic group);
R16 is hydrogen, carboxyl or ester thereof;
R17 is selected from hydrogen, non-interfering substituents, selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C7-C12 aralkyl, C7-C12 alkaryl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, phenyl, tolyl, xylyl, biphenyl, C1-C6 alkoxy, C2-C6 alkenyloxy, C2-C6 alkynyloxy, C2-C12 alkoxyalkyl, C2-C12 alkoxyalkyloxy, C2-C12 alkylcarbonyl, C2-C12 alkylcarbonylamino, C2-C12 alkoxyamino, C2-C12 alkoxyaminocarbonyl, C2-C12 alkylamino, C1-C6 alkylthio, C2-C12 alkylthiocarbonyl, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C2-C6 haloalkoxy, C1-C6 haloalkylsulfonyl, C2-C6 haloalkyl, C1-C6 hydroxyalkyl, —C(O)O(C1-C6 alkyl), —(CH2)n—O—(C1-C6 alkyl), benzyloxy, phenoxy, phenylthio, —CHO, amino, amidino, bromo, carbamyl, carboxyl, carbalkoxy, —(CH2)n—CO2H, chloro, cyano, cyanoguanidinyl, fluoro, guanidino, hydrazide, hydrazino, hydrazido, hydroxy, hydroxyamino, iodo, nitro, phosphono, —SO3H, thioacetal, thiocarbonyl, and C1-C6 carbonyl;
where n is from 1 to 8.

32 more elements

A composition for treatment of disorders associated with apoptosis;

which comprises an N-heterocyclic glyoxylamide compound or a pharmaceutically acceptable salt, solvate, or prodrug derivative thereof selected from the group consisting of compounds (A) through (NN):
(A) [[3-(2-Amino-1,2-dioxoethyl)-2-methyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid,
(B) dl-2-[[3-(2-Amino-1,2-dioxoethyl)-2-methyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]propanoic acid,
(C) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-2-ylmethyl)-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(D) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-3-ylmethyl)-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(E) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-4-ylmethyl)-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(F) [[3-(2-Amino-1,2-dioxoethyl)-1-[(2,6-dichlorophenyl)methyl]-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(G) [[3-(2-Amino-1,2-dioxoethyl)-1-[(4-fluorophenyl)methyl]-2-methyl-1H-indol-4-yl]oxy]acetic acid,
(H) [[3-(2-Amino-1,2-dioxoethyl)-2-methyl-1-[(1-naphthalenyl)methyl]-1H-indol-4-yl]oxy]acetic acid,
(I) [[3-(2-Amino-1,2-dioxoethyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid,
(I′) [[3-(2-Amino-1,2-dioxoethyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid methyl ester
(J) [[3-(2-Amino-1,2-dioxoethyl)-1-[(3-chlorophenyl)methyl]-2-ethyl-1H-indol-4-yl]oxy]acetic acid,
(K) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-2-ylmethyl)-2-ethyl-1H-indol-4-yl]oxy]acetic acid,
(L) [[3-(2-amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-2-ylmethyl)-2-propyl-1H-indol-4-yl]oxy]acetic acid,
(M) [[3-(2-Amino-1,2-dioxoethyl)-2-cyclopropyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid,
(N) [[3-(2-Amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-2-ylmethyl)-2-cyclopropyl-1H-indol-4-yl]oxy]acetic acid,
(O) 4-[[3-(2-Amino-1,2-dioxoethyl)-2-ethyl-1-(phenylmethyl)-1H-indol-5-yl]oxy]butanoic acid,
(P) mixtures of (A) through (O),
(Q) (8-(Carbomethoxymethyloxy)-2-ethyl-3-(o-phenylbenzyl)indolizin-1-yl)glyoxylamide,
(R) (3-Benzyl-8-(carbethoxymethyloxy)-2-ethylindolizin-1-yl)glyoxylamide,
(S) (8-(Carbethoxymethyloxy)-2-ethyl-3-(o-phenylbenzyl)indolizin-1-yl)glyoxylamide,
(T) (3-Benzyl-8-(carbethoxymethyloxy)-2-methylindolizin-1-yl)glyoxylamide,
(U) (8-(Carbethoxymethyloxy)-3-(m-chlorobenzyl)-2-ethylindolizin-1-yl)glyoxylamide,
(V) (8-Carbethoxymethyloxy-2-ethyl-3-(1-naphthylmethyl)indolizin-1-yl)glyoxylamide,
(W) (3-Benzyl-8-(t-butoxycarbonylmethyloxy)-2-ethylindolizin-1-yl)glyoxylamide,
(X) (8-(Carbmethoxymethyloxy)-2-ethyl-3-(m-trifluoromethylbenzyl)indolizin-1-yl)glyoxylamide,
(Y) (8-(Carbmethoxymethyloxy)-2-cyclopropyl-3-(o-phenylbenzyl)indolizin-1-yl)glyoxylamide,
(Z) (3-Benzyl-8-(carboxymethyloxy)-2-ethylindolizin-1-yl)glyoxylamide,
(AA) (8-(Carboxymethyloxy)-2-ethyl-3-(o-phenylbenzyl)indolizin-1-yl)glyoxylamide,
(AA′) (8-Carbomethoxymethyloxy)-2-ethyl-3-(o-phenylbenzyl)indolizin-1-yl)glyoxylamide,
(BB) (3-Benzyl-8-(carboxymethyloxy)-2-methylindolizin-1-yl)glyoxylamide,
(CC) (8-(Carboxymethyloxy)-3-(m-chlorobenzyl)-2-ethylindolizin-1-yl)glyoxylamide,
(DD) (8-(Carboxymethyloxy)-2-ethyl-3-(m-trifluoromethylbenzyl)indolizin-1-yl)glyoxylamide,
(EE) (8-Carboxymethyloxy-2-ethyl-3-(1-naphthylmethyl)indolizin-1-yl)glyoxylamide,
(FF) (8-(Carboxymethyloxy)-2-cyclopropyl-3-(o-phenylbenzyl)indolizin-1-yl) glyoxylamide,
(GG) mixtures of (Q) through (FF),
(HH) [[3-(2-Amino-1,2-dioxoethyl)-6-carboxyl-2-ethyl-1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(II) [[3-(2-Amino-1,2-dioxoethyl)-6-methoxycarbonyl-2-ethyl-1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(JJ) [[3-(2-Amino-1,2-dioxoethyl)-6-ethoxycarbonyl-2-ethyl-1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(KK) [[3-(2-Amino-1,2-dioxoethyl)-6-n-propoxycarbonyl-2-ethyl 1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(LL) [[3-(2-Amino-1,2-dioxoethyl)-6-i-propoxycarbonyl-2-ethyl-1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(MM) [[3-(2-Amino-1,2-dioxoethyl)-6-cyclopropyloxycarbonyl-2-ethyl-1-benzyl-1H-indol-4-yl]oxy]acetic acid,
(NN) mixtures of (HH) through (MM).

40 more elements

Dependencies are inferred from the claim text.

Method for the treatment of disorders associated with apoptosis using N-heterocyclic glyoxylamide compounds

Life of this patent

Abstract

Claims29

Method for the treatment of disorders associated with apoptosis using N-heterocyclic glyoxylamide compounds

Life of this patent

Abstract

Claims29