- Triphenylethanamine Derivatives as Cholesteryl Ester Transfer Protein Inhibitors: Discovery of N-[(1R)-1-(3-Cyclopropoxy-4-fluorophenyl)-1-[3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl]-2-phenylethyl]-4-fluoro-3-(trifluoromethyl)benzamide (BMS-795311)
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Cholesteryl ester transfer protein (CETP) inhibitors raise HDL-C in animals and humans and may be antiatherosclerotic by enhancing reverse cholesterol transport (RCT). In this article, we describe the lead optimization efforts resulting in the discovery o
- Qiao, Jennifer X.,Wang, Tammy C.,Adam, Leonard P.,Chen, Alice Ye A.,Taylor, David S.,Yang, Richard Z.,Zhuang, Shaobin,Sleph, Paul G.,Li, Julia P.,Li, Danshi,Yin, Xiaohong,Chang, Ming,Chen, Xue-Qing,Shen, Hong,Li, Jianqing,Smith, Daniel,Wu, Dauh-Rurng,Leith, Leslie,Harikrishnan, Lalgudi S.,Kamau, Muthoni G.,Miller, Michael M.,Bilder, Donna,Rampulla, Richard,Li, Yi-Xin,Xu, Carrie,Lawrence, R. Michael,Poss, Michael A.,Levesque, Paul,Gordon, David A.,Huang, Christine S.,Finlay, Heather J.,Wexler, Ruth R.,Salvati, Mark E.
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p. 9010 - 9026
(2015/12/09)
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- Diphenylpyridylethanamine (DPPE) derivatives as cholesteryl ester transfer protein (CETP) inhibitors
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A series of diphenylpyridylethanamine (DPPE) derivatives was identified exhibiting potent CETP inhibition. Replacing the labile ester functionality in the initial lead 7 generated a series of amides and ureas. Further optimization of the DPPE series for potency resulted in the discovery of cyclopentylurea 15d, which demonstrated a reduction in cholesterol ester transfer activity (48% of predose level) in hCETP/apoB-100 dual transgenic mice. The PK profile of 15d was suboptimal, and further optimization of the N-terminus resulted in the discovery of amide 20 with an improved PK profile and robust efficacy in transgenic hCETP/apoB-100 mice and in hamsters. Compound 20 demonstrated no significant changes in either mean arterial blood pressure or heart rate in telemeterized rats despite sustained high exposures.
- Harikrishnan, Lalgudi S.,Finlay, Heather J.,Qiao, Jennifer X.,Kamau, Muthoni G.,Jiang, Ji,Wang, Tammy C.,Li, James,Cooper, Christopher B.,Poss, Michael A.,Adam, Leonard P.,Taylor, David S.,Chen, Alice Ye A.,Yin, Xiaohong,Sleph, Paul G.,Yang, Richard Z.,Sitkoff, Doree F.,Galella, Michael A.,Nirschl, David S.,Van Kirk, Katy,Miller, Arthur V.,Huang, Christine S.,Chang, Ming,Chen, Xue-Qing,Salvati, Mark E.,Wexler, Ruth R.,Lawrence, R. Michael
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experimental part
p. 6162 - 6175
(2012/09/07)
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- N-((3-BENZYL)-2,2-(BIS-PHENYL)-PROPAN-1-AMINE DERIVATIVES AS CETP INHIBITORS FOR THE TREATMENT OF ATHEROSCLEROSIS AND CARDIOVASCULAR DISEASES
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Compounds of formula (Ia) and (Ib), wherein A, B, C, R1and R14 are described herein.
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Page/Page column 45
(2010/03/04)
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- Preparation of monofluorophenols via the reaction of difluorobenzene derivatives with potassium trimethylsilanoate
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An efficient synthesis of monofluorophenols via the reaction of difluorobenzene derivatives with potassium trimethylsilanoate in moderate to excellent yields is described. High regioselectivity was observed in some cases. Georg Thieme Verlag Stuttgart.
- Li, Jianqing,Smith, Daniel,Qiao, Jennifer X.,Huang, Stella,Krishnananthan, Subramaniam,Wong, Henry S.,Salvati, Mark E.,Balasubramanian, Balu N.,Chen, Bang-Chi
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body text
p. 633 - 637
(2009/07/01)
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- HETEROCYCLIC CETP INHIBITORS
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Compounds of formula (Ia) and (Ib) wherein A, B, C and R1 are described herein.
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Page/Page column 220-221
(2010/11/27)
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- HETEROCYCLIC CETP INHIBITORS
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Compounds of formula (Ia) and (Ib): wherein A, B, C and Rl are described herein, are suitable as cholesteryl ester transfer protein (CETP) inhibitors.
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Page/Page column 176; 205
(2010/11/27)
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- HETEROCYCLIC CETP INHIBITORS
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Compounds of formula Ia and Ib wherein A, B, C and R1 are described herein.
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Page/Page column 115
(2010/11/27)
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- 3-(2-Acylamino-1-Hydroxyethyl)-Morpholine Derivatives and Their Use as Bace Inhibitors
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The present invention provides BACE inhibitors of Formula (I); methods for their use and preparation, and intermediates useful for their preparation.
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Page/Page column 62
(2008/06/13)
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- Mandelic acid derivatives and their use as throbin inhibitors
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There is provided a compound of formula I wherein Ra, R1, R2, Y and R3 have meanings given in the description and pharmaceutically acceptable derivatives (including prodrugs) thereof, which compounds and derivatives are useful as, or are useful as prodrugs of, competitive inhibitors of trypsin-like proteases, such as thrombin, and thus, in particular, in the treatment of conditions where inhibition of thrombin is required (e.g. thrombosis) or as anticoagulants.
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Page/Page column 32
(2008/06/13)
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- PHARMACEUTICAL COMBINATION
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There is provided a combination product comprising: (1) a compound of claim 1 in WO 02/44145 or a compound of claim 20 in WO 02/44145 (or derivative thereof)or a pharmaceutically-acceptable derivative thereof; and (1) a compound as defined in claim 1 of WO 01/28992 or (2) a compound of Claim 34 of WO 01/28992 or (3) Compound A or B or C or D (or pharmaceutically-acceptable salts thereof) for use in treating arrhythmia or a coagulation controlled complication thereof.
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