A series of P1/P1' substituted cyclic urea analogues were prepared in an attempt to increase the intra-cellular antiviral potency of the nonsymmetrical 3-aminoindazoles DMP 850 and DMP 851. The effect of alkyl substitution of the P1/P1' residues on cellular antiviral potency, protein binding, resistance profile and pharmacokinetics are described.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/s0960-894x(02)01064-8 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Diastereoselective Synthesis of the HIV Protease Inhibitor Darunavir and Related Derivatives via a Titanium Tetrachloride-Mediated Asymmetric Glycolate Aldol Addition Reaction.
J Org Chem
July 2024
Department of Chemistry, Illinois State University, Normal, Illinois 61790-4160, United States.
Darunavir is a potent HIV protease inhibitor that has been established as an effective tool in the fight against the progression of HIV/AIDS in the global community. The successful application of this drug has spurred the development of derivatives wherein strategic regions (e.g.
View Article and Find Full Text PDFStepwise Reversion of Multiply Mutated Recombinant Antitrypsin Reveals a Selective Inhibitor of Coagulation Factor XIa as Active as the M358R Variant.
Front Cardiovasc Med
March 2021
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
Alpha-1 antitrypsin (AAT, also known as alpha-1 proteinase inhibitor or SERPINA1) is the most abundant member of the serpin superfamily found in human plasma. The naturally occurring variant AAT M358R, altered at the P1 position of the critical reactive center loop (RCL), is re-directed away from inhibition of AAT's chief natural target, neutrophil elastase, and toward accelerated inhibition of thrombin (FIIa), kallikrein (Kal), and other proteases such as factor XIa (FXIa). FXIa is an emerging target for the development of antithrombotic agents, since patients with FXI deficiency are protected from thromboembolic disease and do not exhibit a strong bleeding tendency.
View Article and Find Full Text PDFAmino acid substitutions in VP2, VP1, and 2C attenuate a Coxsackievirus A16 in mice.
Microb Pathog
January 2021
Laboratory of Viral Vaccine Research, Wuhan Institute of Biological Products (WIBP) Co. Ltd., Wuhan, 430207, China. Electronic address:
Coxsackievirus A16 (CVA16) is one of the major etiological agents of hand, foot and mouth disease (HFMD), a common acute infectious disease affecting infants and young children. Severe symptoms of the central nervous system may develop and even lead to death. Here, a plaque-purified CVA16 strain, L731-P1 (P1), was serially passaged in Vero cells for six times and passage 6 (P6) stock became highly attenuated in newborn mice.
View Article and Find Full Text PDFCloning of a novel trypsin inhibitor from the Traditional Chinese medicine decoction pieces, Radix Trichosanthis.
Anal Biochem
August 2019
Natural Drug Discovery Group, School of Pharmacy, Queen's University Belfast, Belfast, Northern Ireland, UK.
Most herbs of traditional Chinese medicine (TCM) are used as air-dried decoction pieces that are manufactured and kept at ambient temperature for long periods. Given the ability of some desiccation-tolerant plants to conserve RNA, it could be worthwhile to isolate mRNA from TCM decoction pieces as part of a transcriptomic strategy to identify new substances with potential pharmaceutical application. Here, we report the molecular cloning of a novel trypsin inhibitor (as the probable alleleic variants TKTI-2 and TKTI-3) from the decoction piece of Radix Trichosanthis, representing the dried root of Trichosanthes kirilowii.
View Article and Find Full Text PDFReducing proteolytic liability of a MMP-14 inhibitory antibody by site-saturation mutagenesis.
Protein Sci
March 2019
Department of Chemical and Environmental Engineering, University of California, Riverside, Riverside, California, 92521.
Playing pivotal roles in tumor growth and metastasis, matrix metalloproteinase-14 (MMP-14) is an important cancer target. Potent inhibitory Fab 3A2 with therapy-desired high selectivity has been isolated from a synthetic antibody library carrying long CDR-H3s. However, like many standard mechanism protease inhibitors, Fab 3A2 can be cleaved by high concentrations of MMP-14 after extended incubation at acidic pH.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!