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US 2003/0153770 A1Published application
Novel sPLA2 inhibitors
AssigneeEli Lilly and Company
InventorsHo-Shen Lin, Michael Enrico Richett
Life of this patent
Estimating the term…
Abstract
A class of novel indole 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.
Claims27
An indole compound represented by the formula (I), or a pharmaceutically acceptable salt, solvate, or prodrug 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 where R11 is a group selected from (a) or (b);
- R2 is hydrogen, or a group containing 1 to 4 non-hydrogen atoms plus any required 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 a group represented by the formulae,
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- wherein, X is oxygen or sulfur;
- and Ra is selected from hydrogen, C1-C8 alkyl, aryl, C1-C8 alkaryl, C1-C8 alkoxy, aralkyl and —CN;
- R4 is the group, -(Lc)-(acylamino acid group);
- wherein -(Lc)-, is an acylamino acid linker having an acylamino acid linker length of 1 to 8;
- R5 is selected from hydrogen, a non-interfering substituent, or the group, -(La)-(acidic group);
- wherein -(La)-, is an acid linker having an acid linker length of 1 to 8;
- R6 and R7 are selected from hydrogen, non-interfering substituent, carbocyclic radical, carbocyclic radical substituted with non-interfering substituent(s), heterocyclic radicals, and heterocyclic radical substituted with non-interfering substituent(s).
18 more elements
An indole compound represented by the formula (II), or a pharmaceutically acceptable salt, solvate, or prodrug derivative thereof;
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- wherein
- R22 is selected from hydrogen, methyl, ethyl, propyl, isopropyl, cyclopropyl, —F, —CF3, —Cl, —Br, or —O—CH3;
- R4a is hydrogen;
- and
- NR4b is an amino acid residue of a natural or unnatural amino acid with the nitrogen atom being part of the amino group of the amino acid, and -(Lc)- is a divalent group selected from;
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- where R40, R41, R42, and R43 are each independently selected from hydrogen or C1-C8 alkyl.
- R16 is selected from hydrogen, C1-C8 alkyl, C1-C8 alkoxy, C1-C8 alkylthio C1-C8 haloalkyl, C1-C8 hydroxyalkyl, and halo.
- R13 is selected from hydrogen and C1-C8 alkyl, C1-C8 alkoxy, —S—(C1-C8 alkyl), C1-C8 haloalkyl, C1-C8 hydroxyalkyl, phenyl, halophenyl, and halo, and t is an integer from 0 to 5.
7 more elements
An indole compound represented by the formulae (C1), (C2), (C3), (C4), (C5), (C6), (C7), (C8), (C9), (C10) or (C11);
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- or pharmaceutically acceptable salts or prodrugs thereof.
Dependencies are inferred from the claim text.