- Chiral purification method of drug intermediate
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The invention provides a chiral purification method of a drug intermediate. The chiral purification method of the drug intermediate comprises the following steps: (1) adding a low-optical-purity compound as shown in a formula A4 into a solvent A, carrying
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Page/Page column 7-13
(2020/06/02)
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- Can We Make Small Molecules Lean? Optimization of a Highly Lipophilic TarO Inhibitor
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We describe our optimization efforts to improve the physicochemical properties, solubility, and off-target profile of 1, an inhibitor of TarO, an early stage enzyme in the biosynthetic pathway for wall teichoic acid (WTA) synthesis. Compound 1 displayed a TarO IC50 of 125 nM in an enzyme assay and possessed very high lipophilicity (clogP = 7.1) with no measurable solubility in PBS buffer. Structure-activity relationship (SAR) studies resulted in a series of compounds with improved lipophilic ligand efficiency (LLE) consistent with the reduction of clogP. From these efforts, analog 9 was selected for our initial in vivo study, which in combination with subefficacious dose of imipenem (IPM) robustly lowered the bacterial burden in a neutropenic Staphylococci murine infection model. Concurrent with our in vivo optimization effort using 9, we further improved LLE as exemplified by a much more druglike analog 26.
- Mandal, Mihirbaran,Tan, Zheng,Madsen-Duggan, Christina,Buevich, Alexei V.,Caldwell, John P.,Dejesus, Reynalda,Flattery, Amy,Garlisi, Charles G.,Gill, Charles,Ha, Sookhee Nicole,Ho, Ginny,Koseoglu, Sandra,Labroli, Marc,Basu, Kallol,Lee, Sang Ho,Liang, Lianzhu,Liu, Jenny,Mayhood, Todd,McGuinness, Debra,McLaren, David G.,Wen, Xiujuan,Parmee, Emma,Rindgen, Diane,Roemer, Terry,Sheth, Payal,Tawa, Paul,Tata, James,Yang, Christine,Yang, Shu-Wei,Xiao, Li,Wang, Hao,Tan, Christopher,Tang, Haifeng,Walsh, Paul,Walsh, Erika,Wu, Jin,Su, Jing
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p. 3851 - 3865
(2017/05/19)
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- Method for preparing arene beta-amino alcohol of optical voidness
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The invention discloses a method for preparing arene beta-amino alcohol of optical voidness. The method is characterized by comprising the following steps that a D or L-amino acid initial material reacts with benzyl chloroformate CBz-Cl or BOC acid anhydr
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- PROCESS FOR PREPARATION OF ANACETRAPIB AND INTERMEDIATES THEREOF
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The present invention relates to a novel process for the preparation of anacetrapib. The present invention also relates to novel intermediate or its salt and its use in the preparation of anacetrapib.
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- NOVEL OXAZOLIDINONE DERIVATIVE AS CETP INHIBITOR, ITS PREPARATION METHOD, AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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Disclosed are a novel oxazolidinone derivative exhibiting inhibitory activity against CETP, a preparation method thereof, and a pharmaceutical composition comprising the same. Exhibiting excellent inhibitory activity against CETP, the oxazolidinone deriva
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- Biphenyl-substituted oxazolidinones as cholesteryl ester transfer protein inhibitors: Modifications of the oxazolidinone ring leading to the discovery of anacetrapib
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The development of the structure-activity studies leading to the discovery of anacetrapib is described. These studies focused on varying the substitution of the oxazolidinone ring of the 5-aryloxazolidinone system. Specifically, it was found that substitution of the 4-position with a methyl group with the cis-stereochemistry relative to the 5-aryl group afforded compounds with increased cholesteryl ester transfer protein (CETP) inhibition potency and a robust in vivo effect on increasing HDL-C levels in transgenic mice expressing cynomolgus monkey CETP.
- Smith, Cameron J.,Ali, Amjad,Hammond, Milton L.,Li, Hong,Lu, Zhijian,Napolitano, Joann,Taylor, Gayle E.,Thompson, Christopher F.,Anderson, Matt S.,Chen, Ying,Eveland, Suzanne S.,Guo, Qiu,Hyland, Sheryl A.,Milot, Denise P.,Sparrow, Carl P.,Wright, Samuel D.,Cumiskey, Anne-Marie,Latham, Melanie,Peterson, Laurence B.,Rosa, Ray,Pivnichny, James V.,Tong, Xinchun,Xu, Suoyu S.,Sinclair, Peter J.
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experimental part
p. 4880 - 4895
(2011/09/20)
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- CYCLIC DIARYL ETHER COMPOUNDS AS ANTAGONISTS OF PROSTAGLANDIN D2 RECEPTORS
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Described herein are compounds that are antagonists of PGD2 receptors. Also described are pharmaceutical compositions and medicaments that include the antagonists of PGD2 receptors described herein, as well as methods of using such antagonists of PGD2 receptors, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other PGD2-dependent or PGD2-mediated conditions or diseases.
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Page/Page column 121
(2009/10/09)
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- ANTAGONISTS OF PROSTAGLANDIN D2 RECEPTORS
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Described herein are compounds that are antagonists of PGD2 receptors. Also described are pharmaceutical compositions and medicaments that include the antagonists of PGD2 receptors described herein, as well as methods of using such a
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Page/Page column 131-132
(2009/10/21)
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- PROCESS FOR SYNTHESIZING A CETP INHIBITOR
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An efficient process is disclosed for producing a compound that is an inhibitor of CETP. The next to last step of the process is the coupling of an oxazolidinone derivative and a triphenyl compound to provide the methyl ester of a compound which is hydrol
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Page/Page column 12
(2008/12/07)
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- CETP INHIBITORS
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Compounds having the structure of Formula (I), including pharmaceutically acceptable salts of the compounds, are CETP inhibitors and are useful for raising HDL-cholesterol, reducing LDL-cholesterol, and for treating or preventing atherosclerosis. In the compounds of Formula (I), B is a cyclic group other than phenyl, and B has a cyclic substituent at a position that is ortho to the position at which B is connected to the remainder of the structure of Formula (I). The 5-membered ring of Formula (I) has a second cyclic substituent in addition to B.
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- CETP INHIBITORS
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Compounds having the structure of Formula I, including pharmaceutically acceptable salts of the compounds, are CETP inhibitors, and are useful for raising HDL-cholesterol, reducing LDL-cholesterol, and for treating or preventing atherosclerosis. The compounds have 3 cyclic groups connected by single bonds, as for example triphenyl, which are attached directly to the ring of formula I or attached at the position B.
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- PROCESS FOR SYNTHESIZING A CETP INHIBITOR
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An efficient process is disclosed for producing a compound that is an inhibitor of CETP. The last step of the process is the coupling of an oxazolidinone derivative with a biphenyl moiety to provide a compound of formula (I). In a specific embodiment of this synthesis, a crystalline product is produced which is characterized as a non-solvated crystalline polymorph.
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Page/Page column 10-11
(2010/11/25)
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- POLYMER FORMULATIONS OF CETP INHIBITORS
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A pharmaceutical composition comprises (a) a CETP inhibiting compound, or a pharmaceutically acceptable salt thereof; (b) a concentration-enhancing polymer; and (c) optionally one or more surfactants; wherein the compound has the structure shown as Formula I below. The composition raises HDL-cholesterol and lowers LDL-cholesterol.
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Page/Page column 23
(2010/11/28)
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- CETP INHIBITORS
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Compounds having the structures of Formula I, including pharmaceutically acceptable salts of the compounds, are CETP inhibitors, and are useful for raising HDL-cholesterol, reducing LDL-cholesterol, and for treating or preventing atherosclerosis: In the compounds of Formula I, B or R2 is a phenyl group which has an ortho aryl, heterocyclic, benzoheterocyclic or benzocycloalky substituent, and one other position on the 5-membered ring has an aromatic, heterocyclic, cycloalkyl, benzoheterocyclic or benzocycloalky substituent connected directly to the ring or attached to the ring through a -CH2-.
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Page/Page column 50-51
(2010/10/19)
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- A practical one-pot process for α-amino aryl ketone synthesis
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An efficient, convenient, high-yielding synthesis of α-amino aryl ketones is described, involving the one-pot deprotonation-transmetallation- arylation of a Weinreb amide while retaining chirality of the original amide.
- Conrad, Karen,Hsiao, Yi,Miller, Ross
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p. 8587 - 8589
(2007/10/03)
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