Search

Your search keyword '"Protack, Tricia"' showing total 4 results
Start Over Author "Protack, Tricia" Journal journal of medicinal chemistry
4 results on '"Protack, Tricia"'

1. 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
Full Text
View/download PDF

2. Discovery and Optimization of Novel Pyrazolopyrimidines as Potent and Orally Bioavailable Allosteric HIV-1 Integrase Inhibitors

Author

Li, Guo, primary, Meanwell, Nicholas A., additional, Krystal, Mark R., additional, Langley, David R., additional, Naidu, B. Narasimhulu, additional, Sivaprakasam, Prasanna, additional, Lewis, Hal, additional, Kish, Kevin, additional, Khan, Javed A., additional, Ng, Alicia, additional, Trainor, George L., additional, Cianci, Christopher, additional, Dicker, Ira B., additional, Walker, Michael A., additional, Lin, Zeyu, additional, Protack, Tricia, additional, Discotto, Linda, additional, Jenkins, Susan, additional, Gerritz, Samuel W., additional, and Pendri, Annapurna, additional

Published
2020
Full Text
View/download PDF

3. 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
Full Text
View/download PDF

4. 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
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results