569688-69-3Relevant academic research and scientific papers
INDANE DERIVATIVES AND THE USE THEREOF AS SOLUBLE GUANYLATE CYCLASE ACTIVATORS
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Page/Page column 61; 62, (2017/07/14)
The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof; a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.
7-HYDROXY-INDOLINYL ANTAGONISTS OF P2Y1 RECEPTOR
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, (2014/02/16)
The present invention provides compounds of Formula (I): Formula (I) as defined in the specification and compositions comprising any of such novel compounds. These compounds are antagonists of P2Y1 receptor which may be used medicaments.
Discovery of 4-Aryl-7-hydroxyindoline-based P2Y1 antagonists as novel antiplatelet agents
Yang, Wu,Wang, Yufeng,Lai, Amy,Qiao, Jennifer X.,Wang, Tammy C.,Hua, Ji,Price, Laura A.,Shen, Hong,Chen, Xue-Qing,Wong, Pancras,Crain, Earl,Watson, Carol,Huang, Christine S.,Seiffert, Dietmar A.,Rehfuss, Robert,Wexler, Ruth R.,Lam, Patrick Y. S.
, p. 6150 - 6164 (2014/08/18)
Adenosine diphosphate (ADP)-mediated platelet aggregation is signaled through two distinct G protein-coupled receptors (GPCR) on the platelet surface: P2Y12 and P2Y1. Blocking P2Y12 receptor is a clinically well-validated strategy for antithrombotic therapy. P2Y1 antagonists have been shown to have the potential to provide equivalent antithrombotic efficacy as P2Y12 inhibitors with reduced bleeding in preclinical animal models. We have previously reported the discovery of a potent and orally bioavailable P2Y1 antagonist, 1. This paper describes further optimization of 1 by introducing 4-aryl groups at the hydroxylindoline in two series. In the neutral series, 10q was identified with excellent potency and desirable pharmacokinetic (PK) profile. It also demonstrated similar antithrombotic efficacy with less bleeding compared with the known P2Y 12 antagonist prasugrel in rabbit efficacy/bleeding models. In the basic series, 20c (BMS-884775) was discovered with an improved PK and liability profile over 1. These results support P2Y1 antagonism as a promising new antiplatelet target.
Telescoped flow process for the syntheses of N-aryl pyrazoles
Li, Bryan,Widlicka, Daniel,Boucher, Steven,Hayward, Cheryl,Lucas, John,Murray, John C.,O'Neil, Brian T.,Pfisterer, David,Samp, Lacey,Vanalsten, John,Xiang, Yanqiao,Young, Joseph
, p. 2031 - 2035 (2013/02/25)
N-Aryl pyrazoles were prepared from anilines in a three step telescoped approach. An aniline was diazotized to give the diazonium fluoroborate, followed by reduction with tin(II) chloride to give the corresponding hydrazine, which in turn reacted with a ketoenamine to give the N-aryl pyrazole. The deprotection of the methyl ether was accomplished with PhBCl2 to give the final product. The continuous flow methodology was used to minimize accumulation of the highly energetic and potentially explosive diazonium salt and hydrazine intermediates to enable the safe scale-up of N-aryl pyrazoles. The heterogeneous reaction mixture was successfully handled in both lab scale and production scale. A continuous extraction was employed to remove organic impurities from the diazotization step, which eliminated the need for chromatography in the purification of the final N-aryl pyrazole.
