3418-69-7Relevant academic research and scientific papers
(7-Benzyloxy-2,3-dihydro- 1H -pyrrolo[1,2-a]indol-1-yl)acetic acids as S1P1 functional antagonists
Buzard, Daniel J.,Lopez, Luis,Moody, Jeanne,Kawasaki, Andrew,Schrader, Thomas O.,Kasem, Michelle,Johnson, Ben,Zhu, Xiuwen,Thoresen, Lars,Kim, Sun Hee,Gharbaoui, Tawfik,Sengupta, Dipanjan,Calvano, Lorene,Krishnan, Ashwin,Gao, Yinghong,Semple, Graeme,Edwards, Jeff,Barden, Jeremy,Morgan, Michael,Usmani, Khawja,Chen, Chuan,Sadeque, Abu,Chen, Weichao,Christopher, Ronald J.,Thatte, Jayant,Fu, Lixia,Solomon, Michelle,Whelan, Kevin,Al-Shamma, Hussien,Gatlin, Joel,Gaidarov, Ibragim,Anthony, Todd,Le, Minh,Unett, David J.,Stirn, Scott,Blackburn, Anthony,Behan, Dominic P.,Jones, Robert M.
, p. 1334 - 1339 (2015/02/02)
S1P1 is a validated target for treatment of autoimmune disease, and functional antagonists with superior safety and pharmacokinetic properties are being sought as second generation therapeutics. We describe the discovery and optimization of (7-benzyloxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic acids as potent, centrally available, direct acting S1P1 functional antagonists, with favorable pharmacokinetic and safety properties.
Complementary asymmetric routes to (R)-2-(7-hydroxy-2,3-dihydro-1 H-pyrrolo[1,2-a]indol-1-yl)acetate
Schrader, Thomas O.,Johnson, Benjamin R.,Lopez, Luis,Kasem, Michelle,Gharbaoui, Tawfik,Sengupta, Dipanjan,Buzard, Daniel,Basmadjian, Christine,Jones, Robert M.
, p. 6306 - 6309 (2013/02/25)
Two distinct and scalable enantioselective approaches to the tricyclic indole (R)-2-(7-hydroxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate, an important synthon for a preclinical S1P1 receptor agonist, are reported. Route 1 employs a modified version of Smith's modular 2-substituted indole synthesis as the key transformation. Route 2 involves a highly enantioselective CuH-catalyzed 1,4-hydrosilylation as the stereodefining step. Both routes can be performed without chromatography to provide multigram quantities of the tricycle in ≥98% ee.
PROCESSES FOR THE PREPARATION OF S1P1 RECEPTOR MODULATORS AND CRYSTALLINE FORMS THEREOF
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, (2011/10/03)
The present invention relates to salts, processes, and process intermediates useful in the preparation of (R)-2-(9-chloro-7-(4-isopropoxy-3-(trifluoromethyl)benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic acid of Formula (Ia), salts, and crystalline forms thereof. The compound (R)-2-(9-chloro-7-(4-isopropoxy-3-(trifluoromethyl)benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic acid has been identified as an S1P1 receptor modulator that is useful in the treatment of S1P1 receptor-associated disorders, for example, diseases and disorders mediated by lymphocytes, transplant rejection, autoimmune diseases and disorders, inflammatory diseases and disorders (e.g., acute and chronic inflammatory conditions), cancer, and conditions characterized by an underlying defect in vascular integrity or that are associated with angiogenesis such as may be pathologic (e.g., as may occur in inflammation, tumor development, and atherosclerosis).
SUBSTITUTED TRICYCLIC ACID DERIVATIVES AS S1P1 RECEPTOR AGONISTS USEFUL IN THE TREATMENT OF AUTOIMMUNE AND INFLAMMATORY DISORDERS
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Page/Page column 32, (2011/07/08)
The present invention relates to certain substituted tricyclic acid derivatives of Formula (I) and pharmaceutically acceptable salts thereof, which exhibit useful pharmacological properties, for example, as agonists of the S1P1 receptor. Also provided by the present invention are pharmaceutical compositions containing compounds of the invention, and methods of using the compounds and compositions of the invention in the treatment of S1P1-associated disorders, for example, psoriasis, rheumatoid arthritis, Crohn's disease, transplant rejection, multiple sclerosis, systemic lupus erythematosus, ulcerative colitis, type I diabetes, acne, myocardial ischemia-reperfusion injury, hypertensive nephropathy, glomerulosclerosis, gastritis, polymyositis, thyroiditis, vitiligo, hepatitis, biliary cirrhosis, microbial infections and associated diseases, viral infections and associated diseases, diseases and disorders mediated by lymphocytes, auto immune diseases, inflammatory diseases, and cancer.
