172732-60-4

Upstream product

• 936625-39-7 (3-aminooxalyl-1-benzyl-2-methyl-1H-indol-4-yloxy)-acetic acid tert-butyl ester 
• 35320-67-3 4-hydroxy-2-methyl-1H-indole 
• 17897-50-6 4-methoxy-2-methylindole 
• 936567-84-9 2-(3-aminooxalyl-1-benzyl-2-methyl-1H-indol-4-yloxy)-malonic acid dibenzyl ester 
• 1027514-58-4 (1-Benzyl-3-chlorooxalyl-2-methyl-1H-indol-4-yloxy)-acetic acid methyl ester 
• 172732-79-5 ((2-methyl-1-(phenylmethyl)-1H-indol-4-yl)oxy)acetic acid methyl ester 
• 172732-77-3 4-Methoxy-2-methyl-1-(phenylmethyl)-1H-indole 
• 172732-78-4 4-hydroxy-2-methyl-1-(phenylmethyl)-1H-indole 
• 100-44-7 benzyl chloride 
• 889675-13-2 tert-butyl ({3-[amino(oxo)acetyl]-2-methyl-1H-indol-4-yl}oxy)acetate 
• 697753-60-9 tert-butyl 2-[(2-methyl-1H-indol-4-yl)oxy]acetate 
• 172732-80-8 ((3-(2-Amino-1,2-dioxoethyl)-2-methyl-1-(phenylmethyl)-1H-indol-4-yl)oxy)-acetic acid methyl ester 

Downstream Products

• 936625-86-4 1-benzyl-2-methyl-4-leucine methyl ester amidoylmethyloxy-IH-indol-3-glyoxylamide 
• 936625-85-3 1-benzyl-2-methyl-4-aspartic acid dibenzyl ester amidoylmethyloxy-1H-indol-3-glyoxylamide 

Relevant academic research and scientific papers

PHOSPHOLIPASE INHIBITORS, INCLUDING MULTI-VALENT PHOSPHOLIPASE INHIBITORS, AND USE THEREOF, INCLUDING AS LUMEN-LOCALIZED PHOSPHOLIPASE INHIBITORS

The present invention provides methods and compositions for the treatment of phospholipase-related conditions. In particular, the invention provides a method of treating insulin-related, weight-related conditions and/or cholesterol-related conditions in an animal subject. The method generally involves the administration of a non-absorbed and/or effluxed phospholipase A2 inhibitor that is localized in a gastrointestinal lumen.

INDOLE COMPOUNDS HAVING C4-ACIDIC SUBSTITUENTS AND USE THEREOF AS PHOSPHOLIPASE-A2 INHIBITORS

Indole and indole-related compounds, compositions and methods are disclosed. The compounds of the invention are useful as phospholipase inhibitors. The compounds and compositions of the invention are useful for treatment of phospholipase-related conditions, such as insulin-related, weight-related and/or cholesterol-related conditions in an animal subject.

The first potent inhibitor of mammalian group X secreted phospholipase A2: Elucidation of sites for enhanced binding

Using the X-ray structure of human group X secreted phospholipase A 2 (hGX), we carried out structure-based design of indole-based inhibitors and prepared the compounds using a new synthetic route. The most potent compound inhibited hGX and the mouse orthologue with an IC50 of 75 nM. This compound is the most potent hGX inhibitor reported to date and was also found to inhibit a subset of the other mouse and human SPLA 2S.

Inhibition of the complete set of mammalian secreted phospholipases A 2 by indole analogues: A structure-guided study

Structure-guided design was employed in a search for potent and selective inhibitors of mammalian secreted phospholipases A2 (sPLA 2s). Using the X-ray structures of human groups IIA and X sPLA 2s (hGIIA and hGX) as templates, homology structural models were made for the other human and mouse sPLA2s (hGIB, mGIB, mGIIA, mGIIC, hGIID, mGIID, hGIIE, mGIIE, hGIIF, mGIIF, hGV, mGV, and mGX). Me-Indoxam is a previously discovered indole analogue that binds tightly to many sPLA 2s, and the X-ray structure of the hGX-Me-Indoxam complex was determined at a resolution of 2.0 A. Modeling suggests that the residues near the N1-substituent of Me-Indoxam vary significantly among the mammalian sPLA2s, and therefore a library of 83 N1- variants was prepared by parallel synthesis. Several Me-Indoxam analogues bearing a 4-(2-oxy-ethanoic acid) side chain were potent inhibitors (IC 50 5 μM) hGIID, mGIID, hGIIF, and mGIIF. Me-Indoxam analogues bearing a 5-(4-oxy-butanoic acid) side chain were generally less potent inhibitors. Although no compounds were found to be highly specific for a single human or mouse sPLA2, combinations of Me-Indoxam analogues were discovered that could be used to distinguish the action of various sPLA2s in cellular events. For example, Me-Indoxam and compound 5 are approximately 5-fold more potent on hGIIA than on hGV, and compound 21 is 10-fold more potent on hGV versus hGIIA.

Method for treating sepsis

A novel method of treating and/or preventing sepsis.

Method for the treatment of renal dysfunction with spla2 inhibitors

A method is disclosed for the treatment of of the symptoms associated with renal dysfunction by administering to an animal in need thereof a therapeutically effective amount of a sPLA2 inhibitor, such as a 1H-indole-3-glyoxylamide.

METHOD FOR TRATMENT OF NON-RHEUMATOID ARTHRITIS

A method is disclosed for the treatment of non-rheumatoid arthritis by administering to a mammal in need thereof a therapeutically effective amount of an sPLA 2 inhibitor.

Method for the treatment of cystic fibrosis

A method is disclosed for the treatment of cystic fibrosis by administering to a human in need thereof a therapeutically effective amount of an sPLA2inhibitor, such as a 1H-indole-3-glyoxylamide.

SPLA2 inhibitor compounds for treatment of disease

The present invention is directed to compounds for treating inflammatory bowel disease. More specifically, the present invention is directed to 1H-indole-3-glyoxyamide compounds a sPLA2inhibitors for treating inflammatory bowel disease.

Treatment for alzheimer's disease

This invention is a method of treating a mammal, including a human, susceptible to having Alzheimer's disease, to prevent or delay the onset of Alzheimer's disease; said method comprising administering to said mammal a prophylactically effective amount of