- Nucleus-independent chemical shift (NICS) as a criterion for the design of new antifungal benzofuranones
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The assertion made by Wu et al. that aromaticity may have considerable implications for molecular design motivated us to use nucleus-independent chemical shifts (NICS) as an aromaticity criterion to evaluate the antifungal activity of two series of indol-4-ones. A linear regression analysis of NICS and antifungal activity showed that both tested variables were significantly related (p –1 for Candida glabrata, Candida krusei and Candida guilliermondii with compounds 15-32, 15-15 and 15-1. The MIC for filamentous fungi was 1.95 μg·mL–1 for Aspergillus niger for compounds 15-1, 15-33 and 15-34. The results obtained support the use of NICS in the molecular design of compounds with antifungal activity.
- González-Chávez, Marco Martín,González-Chávez, Rodolfo,Méndez, Francisco,Martínez, Roberto,Ni?o-Moreno, Perla Del Carmen,Ojeda-Fuentes, Luis Enrique,Richaud, Arlette,Zerme?o-Macías, María de los ángeles
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- NOVEL IMIDAZOPYRIMIDINE COMPOUNDS AND USES THEREOF
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The present disclosure provides compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. The compounds des
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Page/Page column 88; 89
(2019/06/13)
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- Highlights of the Structure-Activity Relationships of Benzimidazole Linked Pyrrolidines Leading to the Discovery of the Hepatitis C Virus NS5A Inhibitor Pibrentasvir (ABT-530)
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Curative interferon and ribavirin sparing treatments for hepatitis C virus (HCV)-infected patients require a combination of mechanistically orthogonal direct acting antivirals. A shared component of these treatments is usually an HCV NS5A inhibitor. First generation FDA approved treatments, including the component NS5A inhibitors, do not exhibit equivalent efficacy against HCV virus genotypes 1-6. In particular, these first generation NS5A inhibitors tend to select for viral drug resistance. Ombitasvir is a first generation HCV NS5A inhibitor included as a key component of Viekira Pak for the treatment of patients with HCV genotype 1 infection. Since the launch of next generation HCV treatments, functional cure for genotype 1-6 HCV infections has been achieved, as well as shortened treatment duration across a wider spectrum of genotypes. In this paper, we show how we have modified the anchor, linker, and end-cap architecture of our NS5A inhibitor design template to discover a next generation NS5A inhibitor pibrentasvir (ABT-530), which exhibits potent inhibition of the replication of wild-type genotype 1-6 HCV replicons, as well as improved activity against replicon variants demonstrating resistance against first generation NS5A inhibitors.
- Wagner, Rolf,Randolph, John T.,Patel, Sachin V.,Nelson, Lissa,Matulenko, Mark A.,Keddy, Ryan,Pratt, John K.,Liu, Dachun,Krueger, A. Chris,Donner, Pamela L.,Hutchinson, Douglas K.,Flentge, Charles,Betebenner, David,Rockway, Todd,Maring, Clarence J.,Ng, Teresa I.,Krishnan, Preethi,Pilot-Matias, Tami,Collins, Christine,Panchal, Neeta,Reisch, Thomas,Dekhtyar, Tatyana,Mondal, Rubina,Stolarik, Deanne F.,Gao, Yi,Gao, Wenqing,Beno, David A.,Kati, Warren M.
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supporting information
p. 4052 - 4066
(2018/05/14)
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- Synthesis, spectral characterization and biological evaluation of a novel series of 6-arylsubstituted-3-[2-(4-substitutedphenyl)propan-2-yl]-7H-[1,2,4] triazolo[3,4-b][1,3,4]thiadiazines
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On account of the reported anticancer activity of triazolothiadiazines, we have synthesized a novel series of 6-arylsubstituted-3-[2-(4-substitutedphenyl) propan-2-yl]-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines and tested for in-vitro cytotoxicity by trypan blue exclusion and MTT assay. These compounds were also evaluated for their in-vivo anthelmintic activity, as well as in-vitro antimicrobial studies. Amongst the tested compounds, the compound 7j was the most promising cytotoxic agent with IC50 value of 10.54 μM in MCF-7 cells. The compounds 7l and 7q exhibited excellent anthelmintic activity. The compounds 7d, 7f, 7j, 7l, 7o, 7p and 7r showed good antibacterial activity, whereas compounds 7e and 7k exhibited excellent antifungal activity. The structures of newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR and LCMS analysis.
- Puthiyapurayil, Pushpan,Poojary, Boja,Chikkanna, Chandrashekhar,Buridipad, Sunil Kumar
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p. 407 - 416
(2013/01/15)
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- Anti-Viral Compounds
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Compounds effective in inhibiting replication of Hepatitis C virus (“HCV”) are described. This invention also relates to processes of making such compounds, compositions comprising such compounds, and methods of using such compounds to treat HCV infection.
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- FUSED HETEROCYCLIC COMPOUND HAVING ANTI-HCV EFFECT
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Disclosed is a compound represented by the formula (I) below, a pharmaceutically acceptable salt thereof, or a solvate of them. (I) (In the formula, A represents N or CH; Het represents any one of the following groups: (a), (b), (c), (d), (e), (f), (g), (h), (i), (j), (k) wherein R0 and R respectively represent a hydrogen, an optionally substituted alkyl, an optionally substituted cycloalkyl, an optionally substituted aryl or the like; R1 and R2 respectively represent a hydrogen, an optionally substituted alkyl, an optionally substituted alkenyl, an optionally substituted cycloalkyl, an optionally substituted aryl, an optionally substituted heteroaryl or the like; p is an integer of 0-3; and R3 represents an optionally substituted alkyl or the like.)
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Page/Page column 234-235
(2010/02/15)
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