164082-86-4Relevant academic research and scientific papers
1H-INDOLE-3-GLYOXYLAMIDE SPLA2 INHIBITORS
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, (2008/06/13)
A class of novel 1H-indole-3-glyoxylamides is disclosed together with the use of such indole compounds for inhibiting sPLA2 mediated release of fatty adds for treatment of conditions such as septic shock
1H-INDOLE-3-ACETAMIDE SPLA2 INHIBITORS
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, (2008/06/13)
A class of novel 1-indole-3-acetamides represented by the formula; is disclosed together with the use of such indole compounds for inhibiting sPLA2 mediated release of fatty acids.
Indole inhibitors of human nonpancreatic secretory phospholipase A2. 1. Indole-3-acetamides
Dillard, Robert D.,Bach, Nicholas J.,Draheim, Susan E.,Berry, Dennis R.,Carlson, Donald G.,Chirgadze, Nickolay Y.,Clawson, David K.,Hartley, Lawrence W.,Johnson, Lea M.,Jones, Noel D.,McKinney, Emma R.,Mihelich, Edward D.,Olkowski, Jennifer L.,Schevitz, Richard W.,Smith, Amy C.,Snyder, David W.,Sommers, Cynthia D.,Wery, Jean-Pierre
, p. 5119 - 5136 (2007/10/03)
Phospholipases (PLAs) produce rate-limiting precursors in the biosynthesis of various types of biologically active lipids involved in inflammatory processes. Increased levels of human nonpancreatic secretory phospholipase A2 (hnps-PLA2) have been detected in several pathological conditions. An inhibitor of this enzyme could have therapeutic utility. A broad screening program was carried out to identify chemical structures which could inhibit hnps-PLA2. One of the lead compounds generated by the screening program was 5-methoxy-2-methyl-1-(phenylmethyl)-1H-indole-3-acetic acid (13a). We describe the syntheses, structure-activity relationships, and pharmacological activities of a series of indole-3-acetamides and related compounds derived from this lead. This SAR was undertaken with the aid of X- ray crystal structures of complexes between the inhibitors and hnps-PLA2 which were of great value in directing the SAR.
Indole inhibitors of human nonpancreatic secretory phospholipase A2. 2. Indole-3-acetamides with additional functionality
Dillard, Robert D.,Bach, Nicholas J.,Draheim, Susan E.,Berry, Dennis R.,Carlson, Donald G.,Chirgadze, Nickolay Y.,Clawson, David K.,Hartley, Lawrence W.,Johnson, Lea M.,Jones, Noel D.,McKinney, Emma R.,Mihelich, Edward D.,Olkowski, Jennifer L.,Schevitz, Richard W.,Smith, Amy C.,Snyder, David W.,Sommers, Cynthia D.,Wery, Jean-Pierre
, p. 5137 - 5158 (2007/10/03)
As reported in our previous paper, a series of indole-3-acetamides which possessed potency and selectivity as inhibitors of human nonpancreatic secretory phospholipase A2(hnps-PLA2) was developed. The design of these compounds was based on information derived from x-ray crystal structures determined for complexes between the enzyme and its inhibitors. We describe here the further implementation of this structure-based design strategy and continued SAR development to produce indole-3-acetamides with additional functionalities which provide increased interaction with important residues within the enzyme active site. These efforts led to inhibitors with substantially enhanced potency and selectivity.
