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US 2003/0191175 A1Published application
Indole sPLA2 inhibitors
AssigneeEli Lilly and Company
InventorsEdward David Mihelich, Michael LeRoy Phillips, Alan M. Warshawsky
Life of this patent
Estimating the term…
Abstract
A class of novel acylsulfonaimide substituted indole compounds is disclosed together with the use of such compounds for inhibiting sPLA2 mediated release of fatty acids for treatment of inflammatory diseases such as septic shock.
Drawings
Claims27
An indole compound represented by the formula (I), or a pharmaceutically acceptable salt, or solvate derivative thereof;
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- wherein;
- R1 is selected from groups (a), (b) and (c) wherein;
- (a) is C7-C20 alkyl, C7-C20 haloalkyl, C7-C20 alkenyl, C7-C20 alkynyl, carbocyclic radical, or heterocyclic radical, or
- (b) is a member of (a) substituted with one or more independently selected non-interfering substituents;
- or
- (c) is the group -(L1)—R11;
- where, -(L1)- is a divalent linking group of 1 to 8 atoms and R11 is a group selected from (a) or (b);
- R2 is hydrogen, or a group containing 1 to 4 non-hydrogen atoms;
- R3 is -(L3)- Z, where -(L3)- is a divalent linker group selected from a bond or a divalent group selected from:
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- and Z is selected from acetamide, thioacetamide, glyoxylamide, thioglyoxylamide, hydrazide or thiohydrazide groups represented by the formulae,
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- where R31 and R32 are independently selected from hydrogen, C1-C8 alkyl, C1-C8 haloalkyl, and C3-C4 cycloalkyl, and X is oxygen or sulfur;
- R4 and R5 each independently selected from hydrogen, a non-interfering substituent, or the group, -(La)-(acylsulfonamide group), where -(La)-, is a divalent linker having a linker length of 1 to 8;
- provided that at least one of R4 and R5 must be the group, -(La)-(acylsulfonamide group);
- and
- R6 and R7 are each independently selected from hydrogen, non-interfering substituent, carbocyclic radical, carbocyclic radical substituted with non-interfering substituent, heterocyclic radical, and heterocyclic radical substituted with non-interfering substituent.
15 more elements
A indole compound represented by the formula (II), or a pharmaceutically acceptable salt or solvate thereof;
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- wherein;
- R16 is selected from hydrogen and C1-C8 alkyl, C1-C8 alkoxy, C1-C8 alkylthio C1-C8 haloalkyl, C1-C8 hydroxyalkyl, and halo;
- R44 is methyl, ethyl, phenyl, —CF3;
- -(L4)- is a divalent group selected from,
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- where R40, R41, R42, and R43 are each independently selected from hydrogen, C1-C8 alkyl;
- R22 is selected from hydrogen, methyl, ethyl, propyl, isopropyl, cyclopropyl, —F, —CF3, —Cl, —Br, or —O—CH3;
- and
- R13 is C1-C8 alkyl, C1-C8 alkoxy, —S—(C1-C8 alkyl), C1-C8 haloalkyl, C1-C8 hydroxyalkyl, and halo;
- and t is an integer from 0 to 5.
8 more elements
An indole compound selected from the group consisting of:
- 1-benzyl-2-ethyl-4-methanesulfonamidoylmethyloxy-indole-3-glyoxylamide;
- 1-benzyl-2-ethyl-4-benzenesulfonamidoylmethyloxy-indole-3-glyoxylamide;
- 1-benzyl-2-ethyl-4-trifluoromethanesulfonamidoylmethyloxy-indole-3-glyoxylamide;
- 1-benzyl-2-ethyl-4-(2-methylbenzenesulfonamidoylmethyloxy)-indole-3-glyoxylamide;
- and
- 1-benzyl-2-ethyl-4-(4-(2-aminoethyl)benzenesulfonamidoylmethyloxy)-indole-3-glyoxylamide, hydrochloride salt.
3 more elements
A indole compound represented by the formula (C1);
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Dependencies are inferred from the claim text.