23877-66-9Relevant academic research and scientific papers
BENZOTHIOPHENE ESTROGEN RECEPTOR MODULATORS
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Paragraph 0633-0634, (2018/08/29)
This invention is a benzothiophene estrogen receptor modulator or its pharmaceutically acceptable salt or a pharmaceutically acceptable composition thereof to treat an estrogen-related medical disorder.
HETEROCYCLIC COMPOUNDS AND METHODS OF USE
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Page/Page column 217, (2010/08/04)
In one aspect, the present invention provides for a compound of Formula I; in which the variable X1a, X1b, X1c, X1d, Q, A, R1, B, L, E, and the subscripts m and n have the meanings as described herein. In another aspect, the present invention provides for pharmaceutical compositions comprising compounds of Formula I as well as methods for using compounds of Formula I for the treatment of diseases and conditions (e.g., cancer, thrombocythemia, etc) characterized by the expression or over-expression of Bcl-2 anti-apoptotic proteins, e.g., of anti-apoptotic Bcl-xL proteins.
Identification of a potent, selective, and orally active leukotriene A 4 hydrolase inhibitor with anti-inflammatory activity
Grice, Cheryl A.,Tays, Kevin L.,Savall, Brad M.,Wei, Jianmei,Butler, Christopher R.,Axe, Frank U.,Bembenek, Scott D.,Fourie, Anne M.,Dunford, Paul J.,Lundeen, Katherine,Coles, Fawn,Xue, Xiaohua,Riley, Jason P.,Williams, Kacy N.,Karlsson, Lars,Edwards, James P.
scheme or table, p. 4150 - 4169 (2009/07/19)
LTA4H is a ubiquitously distributed 69 kDa zinc-containing cytosolic enzyme with both hydrolase and aminopeptidase activity. As a hydrolase, LTA4H stereospecifically catalyzes the transformation of the unstable epoxide LTA4 to the diol LTB4, a potent chemoattractant and activator of neutrophils and a chemoattractant of eosinophils, macrophages, mast cells, and T cells. Inhibiting the formation of LTB4 is expected to be beneficial in the treatment of inflammatory diseases such as inflammatory bowel disease (IBD), asthma, and atherosclerosis. We developed a pharmacophore model using a known inhibitor manually docked into the active site of LTA4H to identify a subset of compounds for screening. From this work we identified a series of benzoxazole, benzthiazole, and benzimidazole inhibitors. SAR studies resulted in the identification of several potent inhibitors with an appropriate cross-reactivity profile and excellent PK/PD properties. Our efforts focused on further profiling JNJ 27265732, which showed encouraging efficacy in a disease model relevant to IBD.
LTA4 Hydrolase inhibitors
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Page 65, 107, (2010/01/31)
The present invention provides compounds of the formula Ar1-Q-Ar2-Y-R-Z and pharmaceutically acceptable salts thereof wherein Ar1 and Ar2 are optionally substituted aryl moieties, Z is an optionally substituted nitrogen-containing moiety which may be an acyclic, cyclic or bicyclic amine or an optionally substituted monocyclic or bicyclic nitrogen-containing heteroaromatic moiety; Q is a linking group capable of linking two aryl groups; R is an alkylene moiety; Y is a linking moiety capable of linking an aryl group to an alkylene moiety and wherein Z is bonded to R through a nitrogen atom. The compounds and pharmaceutical compositions of the present invention are useful in the treatment of inflammatory diseases which are mediated by LTB4 production, such as proriasis, ulcerative colitis, IBD and asthma.
Structure-activity relationship studies on 1-[2-(4- phenylphenoxy)ethyl]pyrrolidine (SC-22716), a potent inhibitor of leukotriene A4 (LTA4) hydrolase
Penning, Thomas D.,Chandrakumar, Nizal S.,Chen, Barbara B.,Chen, Helen Y.,Desai, Bipin N.,Djuric, Stevan W.,Docter, Stephen H.,Gasiecki, Alan F.,Haack, Richard A.,Miyashiro, Julie M.,Russell, Mark A.,Yu, Stella S.,Corley, David G.,Durley, Richard C.,Kilpatrick, Brian F.,Parnas, Barry L.,Askonas, Leslie J.,Gierse, James K.,Harding, Elizabeth I.,Highkin, Maureen K.,Kachur, James F.,Kim, Suzanne H.,Krivi, Gwen G.,Villani-Price, Doreen,Pyla, E. Yvonne,Smith, Walter G.,Ghoreishi-Haack, Nayereh S.
, p. 721 - 735 (2007/10/03)
Leukotriene B4 (LTB4) is a pro-inflammatory mediator that has been implicated in the pathogenesis of a number of diseases including inflammatory bowel disease (IBD) and psoriasis. Since the action of LTA4 hydrolase is the rate-limiting step for LTB4 production, this enzyme represents an attractive pharmacological target for the suppression of LTB4 production. From an in- house screening program, SC-22716 (1, 1-[2-(4- phenylphenoxy)ethyl]pyrrolidine) was identified as a potent inhibitor of LTA4 hydrolase. Structure-activity relationship (SAR) studies around this structural class resulted in the identification of a number of novel, potent inhibitors of LTA4 hydrolase, several of which demonstrated good oral activity in a mouse ex vivo whole blood assay.
LTA4 HYDROLASE INHIBITOR PHARMACEUTICAL COMPOSITIONS AND METHODS OF USE
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, (2008/06/13)
The present invention provides compounds of the formula Ar1-Q-Ar2-Y-R-Z and pharmaceutically acceptable salts thereof wherein Ar1 and Ar2 are optionally substituted aryl moieties, Z is an optionally substituted nitrogen-containing moiety which may be an a
LTA4 HYDROLASE INHIBITORS
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, (2008/06/13)
The present invention provides compounds of the formula Ar1?Q?Ar2?Y?R?Z and pharmaceutically acceptable salts thereof wherein Ar1 and Ar2 are optionally substituted aryl moieties, Z is an optionally substituted nitrogen-containing moiety which may be an a
