Search Results - "Pinto, Donald J P"

Preclinical discovery of apixaban, a direct and orally bioavailable factor Xa inhibitor by Wong, Pancras C., Pinto, Donald J. P., Zhang, Donglu

“…Apixaban (BMS-562247; 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro-1 H -pyrazolo[3,4- c ]pyridine-3-carboxamide), a direct…”
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Factor Xa Inhibitors: Next-Generation Antithrombotic Agents by Pinto, Donald J. P, Smallheer, Joanne M, Cheney, Daniel L, Knabb, Robert M, Wexler, Ruth R

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Discovery of 1-(4-Methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro- 1H-pyrazolo[3,4-c]pyridine-3-carboxamide (Apixaban, BMS-562247), a Highly Potent, Selective, Efficacious, and Orally Bioavailable Inhibitor of Blood Coagulation Factor Xa by Pinto, Donald J. P, Orwat, Michael J, Koch, Stephanie, Rossi, Karen A, Alexander, Richard S, Smallwood, Angela, Wong, Pancras C, Rendina, Alan R, Luettgen, Joseph M, Knabb, Robert M, He, Kan, Xin, Baomin, Wexler, Ruth R, Lam, Patrick Y. S

“…Efforts to identify a suitable follow-on compound to razaxaban (compound 4) focused on modification of the carboxamido linker to eliminate potential in vivo…”
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Discovery of 1-(3‘-Aminobenzisoxazol-5‘-yl)-3-trifluoromethyl-N-[2-fluoro-4- [(2‘-dimethylaminomethyl)imidazol-1-yl]phenyl]-1H-pyrazole-5-carboxyamide Hydrochloride (Razaxaban), a Highly Potent, Selective, and Orally Bioavailable Factor Xa Inhibitor by Quan, Mimi L, Lam, Patrick Y. S, Han, Qi, Pinto, Donald J. P, He, Ming Y, Li, Renhua, Ellis, Christopher D, Clark, Charles G, Teleha, Christopher A, Sun, Jung-Hui, Alexander, Richard S, Bai, Steve, Luettgen, Joseph M, Knabb, Robert M, Wong, Pancras C, Wexler, Ruth R

“…Modification of a series of pyrazole factor Xa inhibitors to incorporate an aminobenzisoxazole as the P1 ligand resulted in compounds with improved selectivity…”
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Preclinical pharmacokinetics and pharmacodynamics of apixaban, a potent and selective factor Xa inhibitor by He, Kan, Luettgen, Joseph M., Zhang, Donglu, He, Bing, Grace, James E., Xin, Baomin, Pinto, Donald J. P., Wong, Pancras C., Knabb, Robert M., Lam, Patrick Y. S., Wexler, Ruth R., Grossman, Scott J.

“…Apixaban is a potent, highly selective, reversible, oral, direct factor Xa (fXa) inhibitor in development for thrombosis prevention and treatment. The…”
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Discovery of Milvexian, a High-Affinity, Orally Bioavailable Inhibitor of Factor XIa in Clinical Studies for Antithrombotic Therapy by Dilger, Andrew K, Pabbisetty, Kumar B, Corte, James R, De Lucca, Indawati, Fang, Tianan, Yang, Wu, Pinto, Donald J. P, Wang, Yufeng, Zhu, Yeheng, Mathur, Arvind, Li, Jianqing, Hou, Xiaoping, Smith, Daniel, Sun, Dawn, Zhang, Huiping, Krishnananthan, Subramaniam, Wu, Dauh-Rurng, Myers, Joseph E, Sheriff, Steven, Rossi, Karen A, Chacko, Silvi, Zheng, Joanna J, Galella, Michael A, Ziemba, Theresa, Dierks, Elizabeth A, Bozarth, Jeffrey M, Wu, Yiming, Crain, Earl, Wong, Pancras C, Luettgen, Joseph M, Wexler, Ruth R, Ewing, William R

“…Factor XIa (FXIa) is an enzyme in the coagulation cascade thought to amplify thrombin generation but has a limited role in hemostasis. From preclinical models…”
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Factor XIa Inhibitors as New Anticoagulants by Quan, Mimi L, Pinto, Donald J. P, Smallheer, Joanne M, Ewing, William R, Rossi, Karen A, Luettgen, Joseph M, Seiffert, Dietmar A, Wexler, Ruth R

“…With the introduction of thrombin and factor Xa inhibitors to the oral anticoagulant market, significant improvements in both efficacy and safety have been…”
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Discovery of a Parenteral Small Molecule Coagulation Factor XIa Inhibitor Clinical Candidate (BMS-962212) by Pinto, Donald J. P., Orwat, Michael J., Smith, Leon M., Quan, Mimi L., Lam, Patrick Y. S., Rossi, Karen A., Apedo, Atsu, Bozarth, Jeffrey M., Wu, Yiming, Zheng, Joanna J., Xin, Baomin, Toussaint, Nathalie, Stetsko, Paul, Gudmundsson, Olafur, Maxwell, Brad, Crain, Earl J., Wong, Pancras C., Lou, Zhen, Harper, Timothy W., Chacko, Silvi A., Myers, Joseph E., Sheriff, Steven, Zhang, Huiping, Hou, Xiaoping, Mathur, Arvind, Seiffert, Dietmar A., Wexler, Ruth R., Luettgen, Joseph M., Ewing, William R.

“…Factor XIa (FXIa) is a blood coagulation enzyme that is involved in the amplification of thrombin generation. Mounting evidence suggests that direct inhibition…”
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Structure-Based Design of Macrocyclic Factor XIa Inhibitors: Discovery of the Macrocyclic Amide Linker by Corte, James R, Fang, Tianan, Osuna, Honey, Pinto, Donald J. P, Rossi, Karen A, Myers, Joseph E, Sheriff, Steven, Lou, Zhen, Zheng, Joanna J, Harper, Timothy W, Bozarth, Jeffrey M, Wu, Yiming, Luettgen, Joseph M, Seiffert, Dietmar A, Decicco, Carl P, Wexler, Ruth R, Quan, Mimi L

“…A novel series of macrocyclic FXIa inhibitors was designed based on our lead acyclic phenyl imidazole chemotype. Our initial macrocycles, which were…”
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Potent, Orally Bioavailable, and Efficacious Macrocyclic Inhibitors of Factor XIa. Discovery of Pyridine-Based Macrocycles Possessing Phenylazole Carboxamide P1 Groups by Corte, James R, Pinto, Donald J. P, Fang, Tianan, Osuna, Honey, Yang, Wu, Wang, Yufeng, Lai, Amy, Clark, Charles G, Sun, Jung-Hui, Rampulla, Richard, Mathur, Arvind, Kaspady, Mahammed, Neithnadka, Premsai Rai, Li, Yi-Xin Cindy, Rossi, Karen A, Myers, Joseph E, Sheriff, Steven, Lou, Zhen, Harper, Timothy W, Huang, Christine, Zheng, Joanna J, Bozarth, Jeffrey M, Wu, Yiming, Wong, Pancras C, Crain, Earl J, Seiffert, Dietmar A, Luettgen, Joseph M, Lam, Patrick Y. S, Wexler, Ruth R, Ewing, William R

“…Factor XIa (FXIa) inhibitors are promising novel anticoagulants, which show excellent efficacy in preclinical thrombosis models with minimal effects on…”
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Structure–activity relationship and pharmacokinetic profile of 5-ketopyrazole factor Xa inhibitors by Varnes, Jeffrey G., Wacker, Dean A., Pinto, Donald J.P., Orwat, Michael J., Theroff, Jay P., Wells, Brian, Galemo, Robert A., Luettgen, Joseph M., Knabb, Robert M., Bai, Steven, He, Kan, Lam, Patrick Y.S., Wexler, Ruth R.

“…Efforts to further optimize the clinical candidate razaxaban have led to a new series of pyrazole-based factor Xa (fXa) inhibitors. Designed to prevent the…”
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Discovery of potent, efficacious, and orally bioavailable inhibitors of blood coagulation factor Xa with neutral P1 moieties by Pinto, Donald J.P., Galemmo, Robert A., Quan, Mimi L., Orwat, Michael J., Clark, Charles, Li, Renhua, Wells, Brian, Woerner, Francis, Alexander, Richard S., Rossi, Karen A., Smallwood, Angela, Wong, Pancras C., Luettgen, Joseph M., Rendina, Alan R., Knabb, Robert M., He, Kan, Wexler, Ruth R., Lam, Patrick Y.S.

“…The bicyclic tetrahydropyrazolopiperidinone scaffold allowed for the incorporation of multiple neutral P1 moieties with subnanomolar binding affinities for…”
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Orally bioavailable pyridine and pyrimidine-based Factor XIa inhibitors: Discovery of the methyl N-phenyl carbamate P2 prime group by 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.

“…[Display omitted] Pyridine-based Factor XIa (FXIa) inhibitor (S)-2 was optimized by modifying the P2 prime, P1, and scaffold regions. This work resulted in the…”
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Orally bioavailable factor Xa inhibitors containing alpha-substituted gem-dimethyl P4 moieties by Orwat, Michael J, Qiao, Jennifer X, He, Kan, Rendina, Alan R, Luettgen, Joseph M, Rossi, Karen A, Xin, Baomin, Knabb, Robert M, Wexler, Ruth R, Lam, Patrick Y S, Pinto, Donald J P

“…In an effort to identify a potential back-up to apixaban (Eliquis®), we explored a series of diversified P4 moieties. Several analogs with substituted…”
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Structure-Based Design of Novel Guanidine/Benzamidine Mimics:  Potent and Orally Bioavailable Factor Xa Inhibitors as Novel Anticoagulants by Lam, Patrick Y. S, Clark, Charles G, Li, Renhua, Pinto, Donald J. P, Orwat, Michael J, Galemmo, Robert A, Fevig, John M, Teleha, Christopher A, Alexander, Richard S, Smallwood, Angela M, Rossi, Karen A, Wright, Matthew R, Bai, Stephen A, He, Kan, Luettgen, Joseph M, Wong, Pancras C, Knabb, Robert M, Wexler, Ruth R

“…As part of an ongoing effort to prepare orally active factor Xa inhibitors using structure-based drug design techniques and molecular recognition principles, a…”
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Structure–activity relationships of anthranilamide-based factor Xa inhibitors containing piperidinone and pyridinone P4 moieties by Corte, James R., Fang, Tianan, Pinto, Donald J.P., Han, Wei, Hu, Zilun, Jiang, Xiang-Jun, Li, Yun-Long, Gauuan, Jolicia F., Hadden, Mark, Orton, Darren, Rendina, Alan R., Luettgen, Joseph M., Wong, Pancras C., He, Kan, Morin, Paul E., Chang, Chong-Hwan, Cheney, Daniel L., Knabb, Robert M., Wexler, Ruth R., Lam, Patrick Y.S.

“…Introduction of the phenyl piperidinone and phenyl pyridinone P4 moieties in the anthranilamide scaffold led to potent, selective, and orally bioavailable…”
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Phenyltriazolinones as potent factor Xa inhibitors by Quan, Mimi L., Pinto, Donald J.P., Rossi, Karen A., Sheriff, Steven, Alexander, Richard S., Amparo, Eugene, Kish, Kevin, Knabb, Robert M., Luettgen, Joseph M., Morin, Paul, Smallwood, Angela, Woerner, Francis J., Wexler, Ruth R.

“…We have discovered that phenyltriazolinone is a novel and potent P 1 moiety for coagulation factor Xa. X-ray structures of the inhibitors with a…”
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Pyrazole-based factor Xa inhibitors containing N-arylpiperidinyl P4 residues by Qiao, Jennifer X., Cheng, Xuhong, Smallheer, Joanne M., Galemmo, Robert A., Drummond, Spencer, Pinto, Donald J.P., Cheney, Daniel L., He, Kan, Wong, Pancras C., Luettgen, Joseph M., Knabb, Robert M., Wexler, Ruth R., Lam, Patrick Y.S.

“…The synthesis, SAR, pharmacokinetic profile, and modeling studies of both monocyclic and fused pyrazoles containing substituted N-arylpiperidinyl P4 moieties…”
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Nonpeptide factor Xa inhibitors III: effects of DPC423, an orally-active pyrazole antithrombotic agent, on arterial thrombosis in rabbits by Wong, Pancras C, Crain, Earl J, Watson, Carol A, Zaspel, Alverna M, Wright, Matthew R, Lam, Patrick Y, Pinto, Donald J P, Wexler, Ruth R, Knabb, Robert M

“…DPC423 [1-[3-(aminomethyl)phenyl]-N-[3-fluoro-2'-(methylsulfonyl)[1,1'-biphenyl]-4-yl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide] is a synthetic,…”
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Structure based design of macrocyclic factor XIa inhibitors: Discovery of cyclic P1 linker moieties with improved oral bioavailability by Clark, Charles G., Rossi, Karen A., Corte, James R., Fang, Tianan, Smallheer, Joanne M., De Lucca, Indawati, Nirschl, David S., Orwat, Michael J., Pinto, Donald J.P., Hu, Zilun, Wang, Yufeng, Yang, Wu, Jeon, Yoon, Ewing, William R., Myers, Joseph E., Sheriff, Steven, Lou, Zhen, Bozarth, Jeffrey M., Wu, Yiming, Rendina, Alan, Harper, Timothy, Zheng, Joanna, Xin, Baomin, Xiang, Qian, Luettgen, Joseph M., Seiffert, Dietmar A., Wexler, Ruth R., Lam, Patrick Y.S.

“…[Display omitted] This manuscript describes the discovery of a series of macrocyclic inhibitors of FXIa with oral bioavailability. Assisted by structure based…”
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