A5016383029- HIV/AIDS drug development and treatment
- HIV Research and Treatment
- Advanced Materials Characterization Techniques
- Drug Solubulity and Delivery Systems
- Chemical Synthesis and Analysis
- Analytical Chemistry and Chromatography
- Crystallization and Solubility Studies
- Polymer crystallization and properties
- Chemical Reactions and Isotopes
- Pharmacological Effects and Toxicity Studies
- Analytical Methods in Pharmaceuticals
- Thermal and Kinetic Analysis
- Advanced NMR Techniques and Applications
- HIV/AIDS Research and Interventions
- Protein Kinase Regulation and GTPase Signaling
- Pharmaceutical studies and practices
- DNA and Nucleic Acid Chemistry
- Pharmacogenetics and Drug Metabolism
- HER2/EGFR in Cancer Research
- Drug Transport and Resistance Mechanisms
- Polymer Nanocomposite Synthesis and Irradiation
- Hepatitis C virus research
- Chemical Synthesis and Characterization
- Solid-state spectroscopy and crystallography
- Polymer Nanocomposites and Properties
Biocon (India)
2018-2024
Bristol-Myers Squibb (India)
2018-2024
Syngene International (India)
2020-2023
University of Iowa
2011-2015
Translational Therapeutics (United States)
2015
Phosphate and amino acid prodrugs of the HIV-1 protease inhibitor (PI) atazanavir (1) were prepared evaluated to address solubility absorption limitations. While phosphate prodrug failed release 1 in rats, introduction a methylene spacer facilitated activation, but parent exposure was lower than that following direct administration 1. Val Val-Val dipeptides imparted low plasma parent, although high, reflecting good absorption. Screening additional acids resulted identification an l-Phe ester...
The discovery of a pan-genotypic hepatitis C virus (HCV) NS3/4A protease inhibitor based on P1–P3 macrocyclic tripeptide motif is described. all-carbon tether linking the subsites 21 functionalized with alkyl substituents, which are shown to effectively modulate both potency and absorption, distribution, metabolism, excretion (ADME) properties. CF3Boc-group that caps P3 amino moiety was discovered be an essential contributor metabolic stability, while positioning methyl group at C1 position...
The pH-dependent solubility of the weakly basic TYK2 inhibitor 1 posed a risk to its advancement, given that drugs with such profiles have exhibited drug–drug interaction (DDI) stomach acid-reducing agents in humans. In rat model pH dependence, preadministration famotidine caused 2.4-fold lower exposure when compared control rats, implying oral absorption can reduce active drug's and translate subtherapeutic treatment. As part mitigation, prodrug strategy was explored by synthesizing...
HIV-1 protease inhibitors (PIs), which include atazanavir (ATV, 1), remain important medicines to treat infection. However, they are characterized by poor oral bioavailability and a need for boosting with pharmacokinetic enhancer, results in additional drug-drug interactions that sometimes difficult manage. We investigated chemo-activated, acyl migration-based prodrug design approach improve the profile of 1 but failed obtain improved over dosing parent drug rats. This strategy was refined...
ABSTRACT The kinetics of formanilides hydrolysis were determined under first‐order conditions in hydrochloric acid (0.01–8 M, 20–60°C) and hydroxide solutions (0.01–3 25 40°C). Under acidic conditions, second‐order specific catalytic constants used to construct Hammett plots. ortho effect was analyzed using the Fujita–Nishioka method. In alkaline solutions, displayed both first‐ dependence concentration. base Ortho effects evaluated for on Formanilide hydrolyzes by catalysis, kinetic study...
Structure–property relationships associated with a series of (carbonyl)oxyalkyl amino acid ester prodrugs the marketed HIV-1 protease inhibitor atazanavir (1), designed to enhance systemic drug delivery, were examined. Compared previously reported prodrugs, optimized candidates delivered significantly enhanced plasma exposure and trough concentration (Cmin at 24 h) 1 in rats while revealing differentiated PK paradigms based on kinetics prodrug activation release. Prodrugs incorporating...