- Orally bioavailable pyridine and pyrimidine-based Factor XIa inhibitors: Discovery of the methyl N-phenyl carbamate P2 prime group
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Pyridine-based Factor XIa (FXIa) inhibitor (S)-2 was optimized by modifying the P2 prime, P1, and scaffold regions. This work resulted in the discovery of the methyl N-phenyl carbamate P2 prime group which maintained FXIa activity, reduced the number of H
- Corte, James R.,Fang, Tianan,Pinto, Donald J.P.,Orwat, Michael J.,Rendina, Alan R.,Luettgen, Joseph M.,Rossi, Karen A.,Wei, Anzhi,Ramamurthy, Vidhyashankar,Myers, Joseph E.,Sheriff, Steven,Narayanan, Rangaraj,Harper, Timothy W.,Zheng, Joanna J.,Li, Yi-Xin,Seiffert, Dietmar A.,Wexler, Ruth R.,Quan, Mimi L.
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p. 2257 - 2272
(2016/04/26)
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- ARYLPROPIONAMIDE, ARYLACRYLAMIDE, ARYLPROPYNAMIDE, OR ARYLMETHYLUREA ANALOGS AS FACTOR XIA INHIBITORS
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The present invention provides compounds of Formula (I): Formula (I) or a stereoisomer, tautomer, pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, L1, M and R11 are as defined herein. The compounds of Formula (I) are selective inhibitors of serine protease enzymes of the coagulation cascade and/or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and/or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.
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Page/Page column 228
(2008/06/13)
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- SIX-MEMBERED HETEROCYCLES USEFUL AS SERINE PROTEASE INHIBITORS
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The present invention provides compounds of Formula (I) or a stereoisomer or pharmaceutically acceptable salt or solvate form thereof, wherein the variables A, L, Z, X1, X2, X3, X4, and X5 are as defined herein. The compounds of Formula (I) are useful as selective inhibitors of serine protease enzymes of the coagulation cascade and/or contact activation system; for example thrombin, factor Xa, factor XIa, factor IXa, factor VIIa and/or plasma kallikrein. In particular, it relates to compounds that are selective factor XIa inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.
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Page/Page column 80
(2010/02/15)
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- 1,4-Silatropy of S-α-silylbenzyl thioesters: A convenient route to silyl enol and dienol ethers accompanied by C-C bond formation via thiocarbonyl ylides
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A novel convenient method for the generation of thiocarbonyl ylides from readily accessible starting materials and the first synthetic application of in situ generated ylides in the synthesis of silyl enol and dienol ethers, accompanied by C-C bond formation, is described. Under completely neutral conditions without any catalyst or additive, thermal reactions of S-α-silylbenzyl thioesters in sealed tubes at 180 °C provided silyl enol and dienol ethers in good to excellent yields with high stereoselectivities. This procedure consists of a multistep reaction in a one-pot process, i.e., 1,4-silatropy of S-α-silylbenzyl thioesters to give thiocarbonyl ylides, 1,3-electrocyclization of the ylides to give thiiranes, and the extrusion of sulfur from thiiranes to give silyl enol and dienol ethers.
- Choi, Jinil,Imai, Eiichiro,Mihara, Masatoshi,Oderaotoshi, Yoji,Minakata, Satoshi,Komatsu, Mitsuo
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p. 6164 - 6171
(2007/10/03)
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