185063-84-7Relevant academic research and scientific papers
Novel 3H-[1,2,3]triazolo[4,5-c]pyridine derivatives as GPR119 agonists: Synthesis and structure-activity/solubility relationships
Matsuda, Daisuke,Kobashi, Yohei,Mikami, Ayako,Kawamura, Madoka,Shiozawa, Fumiyasu,Kawabe, Kenichi,Hamada, Makoto,Nishimoto, Shinichi,Kimura, Kayo,Miyoshi, Masako,Takayama, Noriko,Kakinuma, Hiroyuki,Ohtake, Norikazu
, p. 4339 - 4354 (2017/07/22)
We previously reported a novel series of 1H-pyrazolo[3,4-c]pyridine derivatives and the identification of compound 4b as a highly potent GPR119 agonist. However, the advancement of preclinical evaluations of compound 4b is expected to be difficult because of the compound's significantly poor aqueous solubility (0.71?μM at pH6.8). In this article, we describe the further optimization of compound 4b focusing on the improvement of its aqueous solubility. Optimization of the central spacer, left-hand aryl group and right-hand piperidine N-capping group led to the identification of a potent GPR119 agonist, 3H-[1,2,3]triazolo[4,5-c]pyridine derivative 32o, with improved solubility (15.9?μM at pH6.8).
COMPOUDS AND USES THEREOF IN MODULATING AMYLOID BETA
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Paragraph 0195-0196, (2015/11/16)
Novel compounds, compositions, and kits are provided. Methods of modulating Aβ levels, and methods of treating a disease associated with aberrant Aβ levels are also provided.
INDOLE DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF
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Page/Page column 27-28, (2012/06/01)
A compound (I) of the present invention, which has an EP1 receptor antagonism: [wherein A represents a benzene ring or the like; Y1 represents a C1-6 alkylene group; Y2 represents a single bond or the like; Rsu
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.
