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Your search keyword '"Nowicka-Sans, Beata"' showing total 6 results
Start Over Author "Nowicka-Sans, Beata" Journal journal of medicinal chemistry
6 results on '"Nowicka-Sans, Beata"'

1. 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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2. Inhibitors of HIV-1 Attachment: The Discovery and Development of Temsavir and its Prodrug Fostemsavir

Author

Meanwell, Nicholas A., Krystal, Mark R., Nowicka-Sans, Beata, Langley, David R., Conlon, David A., Eastgate, Martin D., Grasela, Dennis M., Timmins, Peter, Wang, Tao, and Kadow, John F.

Abstract

Human immunodeficiency virus-1 (HIV-1) infection currently requires lifelong therapy with drugs that are used in combination to control viremia. The indole-3-glyoxamide 6was discovered as an inhibitor of HIV-1 infectivity using a phenotypic screen and derivatives of this compound were found to interfere with the HIV-1 entry process by stabilizing a conformation of the virus gp120 protein not recognized by the host cell CD4 receptor. An extensive optimization program led to the identification of temsavir (31), which exhibited an improved antiviral and pharmacokinetic profile compared to 6and was explored in phase 3 clinical trials as the phosphonooxymethyl derivative fostemsavir (35), a prodrug designed to address dissolution- and solubility-limited absorption issues. In this drug annotation, we summarize the structure–activity and structure–liability studies leading to the discovery of 31and the clinical studies conducted with 35that entailed the development of an extended release formulation suitable for phase 3 clinical trials.

Published
2024
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5. Inhibitors of Human Immunodeficiency Virus Type 1 (HIV-1) Attachment. 5. An Evolution from Indole to Azaindoles Leading to the Discovery of 1-(4-Benzoylpiperazin-1-yl)-2-(4,7-dimethoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dione (BMS-488043), a Drug Candidate That Demonstrates Antiviral Activity in HIV-1-Infected Subjects

Author

Wang, Tao, primary, Yin, Zhiwei, additional, Zhang, Zhongxing, additional, Bender, John A., additional, Yang, Zhong, additional, Johnson, Graham, additional, Yang, Zheng, additional, Zadjura, Lisa M., additional, D’Arienzo, Celia J., additional, DiGiugno Parker, Dawn, additional, Gesenberg, Christophe, additional, Yamanaka, Gregory A., additional, Gong, Yi-Fei, additional, Ho, Hsu-Tso, additional, Fang, Hua, additional, Zhou, Nannan, additional, McAuliffe, Brian V., additional, Eggers, Betsy J., additional, Fan, Li, additional, Nowicka-Sans, Beata, additional, Dicker, Ira B., additional, Gao, Qi, additional, Colonno, Richard J., additional, Lin, Pin-Fang, additional, Meanwell, Nicholas A., additional, and Kadow, John F., additional

Published
2009
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6. 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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