Zobrazeno 1 - 10
of 102
pro vyhledávání: '"Patrick Y.S. Lam"'
Autor:
Arunachalam Arumugam, Dietmar A. Seiffert, Arvind Mathur, Joanna J. Zheng, Ruth R. Wexler, Jeon Yoon T, Premsai Rai Neithnadka, Earl J. Crain, Paul J. Gilligan, Patrick Y.S. Lam, Yiming Wu, Mahammed Kaspady, Pancras C. Wong, Tianan Fang, Silvi A. Chacko, William R. Ewing, Pabbisetty Kumar Balashanmuga, Zhen Lou, Steven Sheriff, Joseph M. Luettgen, Joseph E. Myers, Wu Yang, Karen A. Rossi, Richard Rampulla, James R. Corte, Amy Lai, Charles G. Clark, Jeffrey M. Bozarth, Yufeng Wang, Sivashankaran Raju
Publikováno v:
Journal of Medicinal Chemistry. 63:7226-7242
Oral factor XIa (FXIa) inhibitors may provide a promising new antithrombotic therapy with an improved benefit to bleeding risk profile over existing antithrombotic agents. Herein, we report application of a previously disclosed cyclic carbamate P1 li
Autor:
Simon D P Baugh, Michael R. Jackson, Luke Wakeen, Adel A. Rashad, Cox Kristie D, Marilyn Schuman Jorns, Boris Polyak, Patrick Y.S. Lam
Publikováno v:
Cardiovasc Res
Aims Hydrogen sulfide (H2S) is a potent signaling molecule that activates diverse cardioprotective pathways by posttranslational modification (persulfidation) of cysteine residues in upstream protein targets. Heart failure patients with reduced eject
Autor:
Karen A. Rossi, Tianan Fang, Wu Yang, Dietmar A. Seiffert, Yiming Wu, Mimi L. Quan, Zhen Lou, Honey Osuna, Joseph E. Myers, Steven Sheriff, William R. Ewing, Ruth R. Wexler, Joseph M. Luettgen, Amy Lai, Joanna J. Zheng, James R. Corte, Patrick Y.S. Lam, Timothy W. Harper, Yufeng Wang, Jeffrey M. Bozarth
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 27:3833-3839
Optimization of macrocyclic inhibitors of FXIa is described which focused on modifications to both the macrocyclic linker and the P1 group. Increases in potency were discovered through interactions with a key hydrophobic region near the S1 prime pock
Autor:
Tianan Fang, James R. Corte, Paul J. Gilligan, Yoon Jeon, Honey Osuna, Karen A. Rossi, Joseph E. Myers, Steven Sheriff, Zhen Lou, Joanna J. Zheng, Timothy W. Harper, Jeffrey M. Bozarth, Yiming Wu, Joseph M. Luettgen, Dietmar A. Seiffert, Ruth R. Wexler, Patrick Y.S. Lam
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 30:126949
The discovery of orally bioavailable FXIa inhibitors has been a challenge. Herein, we describe our efforts to address this challenge by optimization of our imidazole-based macrocyclic series. Our optimization strategy focused on modifications to the
Autor:
Animesh Goswami, Feng Qiu, Carl P. Decicco, Andrew T. Pudzianowski, Quentin Michaudel, Adrienne A. Tymiak, Patrick Y.S. Lam, Samuel J. Bonacorsi, Yingru Zhang, Benjamin P. Vokits, Bei Wang, Brad D. Maxwell, Bang-Chi Chen, Ronald L. Hanson, Jun Dai, Arvind Mathur, Dauh-Rurng Wu, Scott A. Shaw, W. Griffith Humphreys, Shun Su, Phil S. Baran, Janet Caceres Cortes, Balu Balasubramanian, Ruth R. Wexler, Zhiwei Guo, Rulin Zhao, Dawn Sun, Wenying Li, Li Peng, Kevin Cao
Publikováno v:
The Journal of Organic Chemistry. 80:7019-7032
Clopidogrel is a prodrug anticoagulant with active metabolites that irreversibly inhibit the platelet surface GPCR P2Y12 and thus inhibit platelet activation. However, gaining an understanding of patient response has been limited due to imprecise und
Autor:
Atsu Apedo, Pancras C. Wong, Olafur S. Gudmundsson, Nathalie Toussaint, Yiming Wu, Timothy W. Harper, Silvi A. Chacko, Leon M. Smith, Baomin Xin, Dietmar A. Seiffert, Steven Sheriff, Ruth R. Wexler, William R. Ewing, Jeffrery M. Bozarth, Mimi L. Quan, Zhen Lou, Earl J. Crain, Brad D. Maxwell, Joanna J. Zheng, Arvind Mathur, Paul Stetsko, Joseph E. Myers, Donald J. P. Pinto, Michael J. Orwat, Karen A. Rossi, Patrick Y.S. Lam, Xiaoping Hou, Joseph M. Luettgen, Huiping Zhang
Publikováno v:
Journal of medicinal chemistry. 60(23)
Factor XIa (FXIa) is a blood coagulation enzyme that is involved in the amplification of thrombin generation. Mounting evidence suggests that direct inhibition of FXIa can block pathologic thrombus formation while preserving normal hemostasis. Precli
Autor:
Qian Xiang, Dietmar A. Seiffert, Wu Yang, Tianan Fang, Joseph E. Myers, Joanne M. Smallheer, Patrick Y.S. Lam, Jeon Yoon T, Zhen Lou, Joanna Zheng, Joseph M. Luettgen, Jeffrey M. Bozarth, Steven Sheriff, Yufeng Wang, William R. Ewing, Zilun Hu, Indawati De Lucca, Donald J. P. Pinto, Michael J. Orwat, James R. Corte, Charles G. Clark, Karen A. Rossi, Alan R. Rendina, Timothy W. Harper, Ruth R. Wexler, David S. Nirschl, Baomin Xin, Yiming Wu
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 29:126604
This manuscript describes the discovery of a series of macrocyclic inhibitors of FXIa with oral bioavailability. Assisted by structure based drug design and ligand bound X-ray crystal structures, the group linking the P1 moiety to the macrocyclic cor
Autor:
Patrick Y.S. Lam, John Lloyd, Ming Chang, Qimin Wu, Joanna Zheng, Robert P. Rehfuss, James C. Sutton, Christine Huang, Ji Hua, Laura Price, Zulan Pi, Ruth R. Wexler
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 23:4206-4209
ADP receptors, P2Y1 and P2Y12 have been recognized as potential targets for antithrombotic drugs. A series of P2Y1 antagonists that contain 2-aminothiazoles as urea surrogates were discovered. Extensive SAR of the thiazole ring is described. The most
Autor:
Laura Price, Ruth R. Wexler, Patrick Y.S. Lam, Pancras C. Wong, Dietmar A. Seiffert, Ming Chang, Joanna Zheng, Earl J. Crain, Robert P. Rehfuss, Carol A. Watson, Tammy C. Wang, Gerry Everlof, William A. Schumacher, Christine Huang, Charles G. Clark, Qimin Wu, Anne B. Stewart, Jeffrey S. Bostwick, Jennifer X. Qiao, Ji Jua
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 23:3239-3243
Preclinical data suggests that P2Y1 antagonists, such as diarylurea compound 1, may provide antithrombotic efficacy similar to P2Y12 antagonists and may have the potential of providing reduced bleeding liabilities. This manuscript describes a series
Autor:
Joseph M. Luettgen, Scott J. Grossman, Ruth R. Wexler, Robert M. Knabb, Pancras C. Wong, Donglu Zhang, Patrick Y.S. Lam, Kan He, Bing He, Donald J. P. Pinto, James E. Grace, Baomin Xin
Publikováno v:
European Journal of Drug Metabolism and Pharmacokinetics. 36:129-139
Apixaban is a potent, highly selective, reversible, oral, direct factor Xa (fXa) inhibitor in development for thrombosis prevention and treatment. The preclinical pharmacokinetic (PK) attributes of apixaban feature small volume of distribution (Vd),