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US 6,635,670 B2Granted
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.
Claims6
An indole compound represented by the formula (II), or a pharmaceutically acceptable salt, solvate, or prodrug thereof;
- 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 group with the nitrogen atom being part of the amino group of the amino acid, and —(L4)— is a divalent group selected from;
- 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, Cl-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.
4 more elements
A method of therapeutically reducing the release of sPLA2 initiated fatty acids to treat inflammatory diseases which comprises contacting sPLA2 with a therapeutically effective amount of an indole compound of formula I.
A compound selected from the group consisting of:
- N-[2-[[3-(Aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetyl]glycine;
- N-[2-[[3-(Aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetyl]glycine methyl ester;
- N-[2-[[3-(Aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetyl]-L-alanine;
- N-[2-[[3-(Aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetyl]-L-alanine methyl ester;
- N-[2-[[3-(Aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetyl]-L-leucine;
- N-[2-[[3-(Aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetyl]-L-leucine methyl ester;
- N-[2-[[3-(Aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetyl]-L-aspartic acid;
- N-[2-[[3-(Aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetyl]-L-aspartic acid dimethyl ester;
- -N-[2-[[3-(Aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetyl]-L-phenylalanine;
- N-[2-[[3-(Aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetyl]-L-phenylalanine methyl ester;
- N-[2-[[3-(Aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetamido]malonic acid;
- [2-[[3-(Aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetamido]malonic acid dimethyl ester;
- N-[2-[[3-(Aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetyl]-L-valine;
- N-[2-[[3-(Aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetyl]-L-valine methyl ester;
- N-[2-[[3-(Aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetyl]-L-isoleucine;
- N-[2-[[3-(Aminooxoacetyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetyl]-L-isoleucine methyl ester.
13 more elements
Dependencies are inferred from the claim text.