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Your search keyword '"Hanumegowda, Umesh"' showing total 10 results
Start Over Author "Hanumegowda, Umesh" Journal journal of medicinal chemistry
10 results on '"Hanumegowda, Umesh"'

1. Potent Long-Acting Inhibitors Targeting the HIV-1 Capsid Based on a Versatile Quinazolin-4-one Scaffold

Author

Gillis, Eric P., primary, Parcella, Kyle, additional, Bowsher, Michael, additional, Cook, James H., additional, Iwuagwu, Christiana, additional, Naidu, B. Narasimhulu, additional, Patel, Manoj, additional, Peese, Kevin, additional, Huang, Haichang, additional, Valera, Lourdes, additional, Wang, Chunfu, additional, Kieltyka, Kasia, additional, Parker, Dawn D., additional, Simmermacher, Jean, additional, Arnoult, Eric, additional, Nolte, Robert T., additional, Wang, Liping, additional, Bender, John A., additional, Frennesson, David B., additional, Saulnier, Mark, additional, Wang, Alan Xiangdong, additional, Meanwell, Nicholas A., additional, Belema, Makonen, additional, Hanumegowda, Umesh, additional, Jenkins, Susan, additional, Krystal, Mark, additional, Kadow, John F., additional, Cockett, Mark, additional, and Fridell, Robert, additional

Published
2023
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2. Synthesis, Structure–Activity Relationships, and In Vivo Evaluation of Novel C-17 Amine Derivatives Based on GSK3640254 as HIV-1 Maturation Inhibitors with Broad Spectrum Activity

Author

Hartz, Richard A., primary, Xu, Li, additional, Sit, Sing-Yuen, additional, Chen, Jie, additional, Venables, Brian L., additional, Lin, Zeyu, additional, Zhang, Sharon, additional, Li, Zhufang, additional, Parker, Dawn, additional, Simmons, Tara S., additional, Jenkins, Susan, additional, Hanumegowda, Umesh M., additional, Dicker, Ira, additional, Krystal, Mark, additional, Meanwell, Nicholas A., additional, and Regueiro-Ren, Alicia, additional

Published
2022
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3. The Discovery of GSK3640254, a Next-Generation Inhibitor of HIV-1 Maturation

Author

Regueiro-Ren, Alicia, primary, Sit, Sing-Yuen, additional, Chen, Yan, additional, Chen, Jie, additional, Swidorski, Jacob J., additional, Liu, Zheng, additional, Venables, Brian L., additional, Sin, Ny, additional, Hartz, Richard A., additional, Protack, Tricia, additional, Lin, Zeyu, additional, Zhang, Sharon, additional, Li, Zhufang, additional, Wu, Dauh-Rurng, additional, Li, Peng, additional, Kempson, James, additional, Hou, Xiaoping, additional, Gupta, Anuradha, additional, Rampulla, Richard, additional, Mathur, Arvind, additional, Park, Hyunsoo, additional, Sarjeant, Amy, additional, Benitex, Yulia, additional, Rahematpura, Sandhya, additional, Parker, Dawn, additional, Phillips, Thomas, additional, Haskell, Roy, additional, Jenkins, Susan, additional, Santone, Kenneth S., additional, Cockett, Mark, additional, Hanumegowda, Umesh, additional, Dicker, Ira, additional, Meanwell, Nicholas A., additional, and Krystal, Mark, additional

Published
2022
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4. Design, Synthesis, and Preclinical Profiling of GSK3739936 (BMS-986180), an Allosteric Inhibitor of HIV-1 Integrase with Broad-Spectrum Activity toward 124/125 Polymorphs

Author

Naidu, B. Narasimhulu, primary, Patel, Manoj, additional, McAuliffe, Brian, additional, Ding, Bo, additional, Cianci, Christopher, additional, Simmermacher, Jean, additional, Jenkins, Susan, additional, Parker, Dawn D., additional, Sivaprakasam, Prasanna, additional, Khan, Javed A., additional, Kish, Kevin, additional, Lewis, Hal, additional, Hanumegowda, Umesh, additional, Krystal, Mark, additional, Meanwell, Nicholas A., additional, and Kadow, John F., additional

Published
2022
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5. Design, Synthesis, and SAR of C-3 Benzoic Acid, C-17 Triterpenoid Derivatives. Identification of the HIV-1 Maturation Inhibitor 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(1,1-Dioxidothiomorpholino)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoic Acid (GSK3532795, BMS-955176)

Author

Regueiro-Ren, Alicia, primary, Swidorski, Jacob J., additional, Liu, Zheng, additional, Chen, Yan, additional, Sin, Ny, additional, Sit, Sing-Yuen, additional, Chen, Jie, additional, Venables, Brian L., additional, Zhu, Juliang, additional, Nowicka-Sans, Beata, additional, Protack, Tricia, additional, Lin, Zeyu, additional, Terry, Brian, additional, Samanta, Himadri, additional, Zhang, Sharon, additional, Li, Zhufang, additional, Easter, John, additional, Beno, Brett R., additional, Arora, Vinod, additional, Huang, Xiaohua S., additional, Rahematpura, Sandhya, additional, Parker, Dawn D., additional, Haskell, Roy, additional, Santone, Kenneth S., additional, Cockett, Mark I., additional, Krystal, Mark, additional, Meanwell, Nicholas A., additional, Jenkins, Susan, additional, Hanumegowda, Umesh, additional, and Dicker, Ira B., additional

Published
2018
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6. Discovery of a Hepatitis C Virus NS5B Replicase Palm Site Allosteric Inhibitor (BMS-929075) Advanced to Phase 1 Clinical Studies

Author

Yeung, Kap-Sun, primary, Beno, Brett R., additional, Parcella, Kyle, additional, Bender, John A., additional, Grant-Young, Katherine A., additional, Nickel, Andrew, additional, Gunaga, Prashantha, additional, Anjanappa, Prakash, additional, Bora, Rajesh Onkardas, additional, Selvakumar, Kumaravel, additional, Rigat, Karen, additional, Wang, Ying-Kai, additional, Liu, Mengping, additional, Lemm, Julie, additional, Mosure, Kathy, additional, Sheriff, Steven, additional, Wan, Changhong, additional, Witmer, Mark, additional, Kish, Kevin, additional, Hanumegowda, Umesh, additional, Zhuo, Xiaoliang, additional, Shu, Yue-Zhong, additional, Parker, Dawn, additional, Haskell, Roy, additional, Ng, Alicia, additional, Gao, Qi, additional, Colston, Elizabeth, additional, Raybon, Joseph, additional, Grasela, Dennis M., additional, Santone, Kenneth, additional, Gao, Min, additional, Meanwell, Nicholas A., additional, Sinz, Michael, additional, Soars, Matthew G., additional, Knipe, Jay O., additional, Roberts, Susan B., additional, and Kadow, John F., additional

Published
2017
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7. Discovery of a Hepatitis C Virus NS5B Replicase Palm Site Allosteric Inhibitor (BMS-929075) Advanced to Phase 1 Clinical Studies.

Author

Kap-Sun Yeung, Beno, Brett R., Parcella, Kyle, Bender, John A., Grant-Young, Katherine A., Nickel, Andrew, Gunaga, Prashantha, Anjanappa, Prakash, Bora, Rajesh Onkardas, Selvakumar, Kumaravel, Rigat, Karen, Ying-Kai Wang, Mengping Liu, Lemm, Julie, Mosure, Kathy, Sheriff, Steven, Changhong Wan, Witmer, Mark, Kish, Kevin, and Hanumegowda, Umesh

Published
2017
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8. Discovery and Preclinical Characterization of the Cyclopropylindolobenzazepine BMS-791325, A Potent Allosteric Inhibitor of the Hepatitis C Virus NS5B Polymerase

Author

Gentles, Robert G., primary, Ding, Min, additional, Bender, John A., additional, Bergstrom, Carl P., additional, Grant-Young, Katharine, additional, Hewawasam, Piyasena, additional, Hudyma, Thomas, additional, Martin, Scott, additional, Nickel, Andrew, additional, Regueiro-Ren, Alicia, additional, Tu, Yong, additional, Yang, Zhong, additional, Yeung, Kap-Sun, additional, Zheng, Xiaofan, additional, Chao, Sam, additional, Sun, Jung-Hui, additional, Beno, Brett R., additional, Camac, Daniel M., additional, Chang, Chong-Hwan, additional, Gao, Mian, additional, Morin, Paul E., additional, Sheriff, Steven, additional, Tredup, Jeff, additional, Wan, John, additional, Witmer, Mark R., additional, Xie, Dianlin, additional, Hanumegowda, Umesh, additional, Knipe, Jay, additional, Mosure, Kathy, additional, Santone, Kenneth S., additional, Parker, Dawn D., additional, Zhuo, Xiaoliang, additional, Lemm, Julie, additional, Liu, Mengping, additional, Pelosi, Lenore, additional, Rigat, Karen, additional, Voss, Stacey, additional, Wang, Yi, additional, Wang, Ying-Kai, additional, Colonno, Richard J., additional, Gao, Min, additional, Roberts, Susan B., additional, Gao, Qi, additional, Ng, Alicia, additional, Meanwell, Nicholas A, additional, and Kadow, John F., additional

Published
2014
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9. Synthesis, Structure–Activity Relationships, and In VivoEvaluation of Novel C-17 Amine Derivatives Based on GSK3640254 as HIV-1 Maturation Inhibitors with Broad Spectrum Activity

Author

Hartz, Richard A., Xu, Li, Sit, Sing-Yuen, Chen, Jie, Venables, Brian L., Lin, Zeyu, Zhang, Sharon, Li, Zhufang, Parker, Dawn, Simmons, Tara S., Jenkins, Susan, Hanumegowda, Umesh M., Dicker, Ira, Krystal, Mark, Meanwell, Nicholas A., and Regueiro-Ren, Alicia

Abstract

An investigation of the structure–activity relationships of a series of HIV-1 maturation inhibitors (MIs) based on GSK3640254 (4) was conducted by incorporating novel C-17 amine substituents to reduce the overall basicity of the resultant analogues. We found that replacement of the distal amine on the C-17 sidechain present in 4with a tertiary alcohol in combination with either a heterocyclic ring system or a cyclohexyl ring substituted with polar groups provided potent wild-type HIV-1 MIs that also retained excellent potency against a T332S/V362I/prR41G variant, a laboratory strain that served as a surrogate to assess HIV-1 polymorphic virus coverage. Compound 26exhibited broad-spectrum HIV-1 activity against an expanded panel of clinically relevant Gag polymorphic viruses and had the most desirable overall profile in this series of compounds. In pharmacokinetic studies, 26had low clearance and exhibited 24 and 31% oral bioavailability in rats and dogs, respectively.

Published
2022
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10. Design, Synthesis, and SAR of C-3 Benzoic Acid, C-17 Triterpenoid Derivatives. Identification of the HIV-1 Maturation Inhibitor 4-((1 R,3a S,5a R,5b R,7a R,11a S,11b R,13a R,13b R)-3a-((2-(1,1-Dioxidothiomorpholino)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1 H-cyclopenta[ a]chrysen-9-yl)benzoic Acid (GSK3532795, BMS-955176).

Author

Regueiro-Ren A, Swidorski JJ, Liu Z, Chen Y, Sin N, Sit SY, Chen J, Venables BL, Zhu J, Nowicka-Sans B, Protack T, Lin Z, Terry B, Samanta H, Zhang S, Li Z, Easter J, Beno BR, Arora V, Huang XS, Rahematpura S, Parker DD, Haskell R, Santone KS, Cockett MI, Krystal M, Meanwell NA, Jenkins S, Hanumegowda U, and Dicker IB

Subjects
ATP Binding Cassette Transporter, Subfamily B, Member 1 genetics, Administration, Oral, Animals, Anti-HIV Agents pharmacokinetics, Benzoic Acid chemistry, Biological Availability, Chemistry Techniques, Synthetic, Chrysenes pharmacology, Dogs, Drug Design, Drug Stability, HIV-1 drug effects, HIV-1 genetics, Humans, Macaca fascicularis, Male, Mice, Inbred Strains, Mice, Knockout, Microsomes, Liver drug effects, Morpholines pharmacology, Polymorphism, Genetic, Rats, Sprague-Dawley, Triterpenes pharmacology, Anti-HIV Agents chemistry, Anti-HIV Agents pharmacology, Chrysenes chemistry, Morpholines chemistry, Structure-Activity Relationship, Triterpenes chemistry
Abstract

GSK3532795, formerly known as BMS-955176 (1), is a potent, orally active, second-generation HIV-1 maturation inhibitor (MI) that advanced through phase IIb clinical trials. The careful design, selection, and evaluation of substituents appended to the C-3 and C-17 positions of the natural product betulinic acid (3) was critical in attaining a molecule with the desired virological and pharmacokinetic profile. Herein, we highlight the key insights made in the discovery program and detail the evolution of the structure-activity relationships (SARs) that led to the design of the specific C-17 amine moiety in 1. These modifications ultimately enabled the discovery of 1 as a second-generation MI that combines broad coverage of polymorphic viruses (EC 50 <15 nM toward a panel of common polymorphisms representative of 96.5% HIV-1 subtype B virus) with a favorable pharmacokinetic profile in preclinical species.

Published
2018
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