114855-35-5Relevant academic research and scientific papers
Picomolar inhibitors of HIV reverse transcriptase featuring bicyclic replacement of a cyanovinylphenyl group
Lee, Won-Gil,Gallardo-Macias, Ricardo,Frey, Kathleen M.,Spasov, Krasimir A.,Bollini, Mariela,Anderson, Karen S.,Jorgensen, William L.
, p. 16705 - 16713 (2013)
Members of the catechol diether class are highly potent non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs). The most active compounds yield EC50 values below 0.5 nM in assays using human T-cells infected by wild-type HIV-1. However, these compounds such as rilpivirine, the most recently FDA-approved NNRTI, bear a cyanovinylphenyl (CVP) group. This is an uncommon substructure in drugs that gives reactivity concerns. In the present work, computer simulations were used to design bicyclic replacements for the CVP group. The predicted viability of a 2-cyanoindolizinyl alternative was confirmed experimentally and provided compounds with 0.4 nM activity against the wild-type virus. The compounds also performed well with EC50 values of 10 nM against the challenging HIV-1 variant that contains the Lys103Asn/Tyr181Cys double mutation in the RT enzyme. Indolyl and benzofuranyl analogues were also investigated; the most potent compounds in these cases have EC50 values toward wild-type HIV-1 near 10 nM and high-nanomolar activities toward the double-variant. The structural expectations from the modeling were much enhanced by obtaining an X-ray crystal structure at 2.88 A resolution for the complex of the parent 2-cyanoindolizine 10b and HIV-1 RT. The aqueous solubilities of the most potent indolizine analogues were also measured to be ～40 μg/mL, which is similar to that for the approved drug efavirenz and ～1000-fold greater than for rilpivirine.
Synthesis of Tetrasubstituted α,β-Unsaturated Aldehydes via Radical 1,4-Aryl Migration/Trifluoromethylthiolation Cascade Reaction of Aryl Propynyl Ethers
Guo, Chun-Huan,Chen, Dao-Qian,Chen, Si,Liu, Xue-Yuan
, p. 2901 - 2906 (2017)
A one-pot synthesis of tetrasubstituted acrylaldehydes via difunctionalization of aryl propynyl ethers has been achieved, which involves a trifluoromethylthiolation process and a radical 1,4-aryl migration from oxygen to carbon. The reaction shows excellent conversion of aryl propynyl ethers into trifluoromethyl-containing α,β-unsaturated aldehydes through a radical pathway. (Figure presented.).
Synthesis of substituted 3-methylene-2,3-dihydrobenzofurans and 3-methylbenzofurans by rhodium (II)-catalyzed annulation
Chen, Ying-Yu,Chen, Kuan-Lin,Tyan, Yu-Chang,Liang, Chien-Fu,Lin, Po-Chiao
, p. 6210 - 6218 (2015)
Abstract The selective synthesis of substituted 3-methylene-2,3-dihydrobenzofurans and 3-methylbenzofurans has developed through Rh(II)-catalyzed denitrogenative annulation of N-sulfonyl-1,2,3-triazole at ambient to mild heating condition, respectively. F
Electrostatic Control of Regioselectivity in Au(I)-Catalyzed Hydroarylation
Lau, Vivian M.,Pfalzgraff, William C.,Markland, Thomas E.,Kanan, Matthew W.
supporting information, p. 4035 - 4041 (2017/03/31)
Competing pathways in catalytic reactions often involve transition states with very different charge distributions, but this difference is rarely exploited to control selectivity. The proximity of a counterion to a charged catalyst in an ion paired comple
PYRIDINES AND PYRIMIDINES AND USE THEREOF
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Paragraph 0273; 0274, (2017/01/31)
The present disclosure provides pyridines and pyrimidines of Formula I and pharmaceutically acceptable salts and solvates thereof: wherein A, G, W1, W2, W3, and R5 are defined as set forth in the specification. The present disclosure also provides uses of the compounds of Formula I and pharmaceutically acceptable salts and solvates thereof. In certain embodiments, Compounds of the present disclosure are useful for treating pain. In another embodiment, Compounds of the present disclosure are useful for treating a disorder responsive to blockade of sodium channels, or alleviating symptoms of the disorder.
Discovery of Potent and Orally Bioavailable GPR40 Full Agonists Bearing Thiophen-2-ylpropanoic Acid Scaffold
Li, He,Huang, Qi,Chen, Cheng,Xu, Bin,Wang, He-Yao,Long, Ya-Qiu
, p. 2697 - 2717 (2017/04/21)
The free fatty acid receptor GPR40 is predominantly expressed in pancreatic β-cells and enhances insulin secretion in a glucose dependent manner. Therefore, GPR40 agonists are possible novel insulin secretagogues with reduced or no risk of hypoglycemia for the treatment of type 2 diabetes mellitus (T2DM). Chemically and structurally diverse GPR40 agonists with high safety are pursued for the clinical development of GPR40-based pharmacotherapeutics. Herein we report our design and discovery of a new chemotype of GPR40 agonists free of the typical phenylpropanoic acid scaffold. The thiophen-2-ylpropanoic acid containing GPR40 modulators functioned as full agonists with high-efficacy response (Emax) and reduced lipophilicity. Significantly, the lead compound in this series, (R)-7k, exhibited more potent in vitro glucose-stimulated insulin secretion and in vivo glucose-lowering effects (10 mg/kg, po) than the GPR40 partial agonist TAK-875, which was once in phase III clinical trials, and high selectivity over the relevant receptors GPR120 and PPARγ.
PYRIDINES AND PYRIMIDINES AND USE THEREOF
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Page/Page column 69-70, (2015/08/06)
The present disclosure provides pyridines and pyrimidines of Formula I and pharmaceutically acceptable salts and solvates thereof: wherein A, G, W1, W2, W3, and R5 are defined as set forth in the specification. The present disclosure also provides uses of the compounds of Formula I and pharmaceutically acceptable salts and solvates thereof. In certain embodiments, Compounds of the present disclosure are useful for treating pain. In another embodiment, Compounds of the present disclosure are useful for treating a disorder responsive to blockade of sodium channels, or alleviating symptoms of the disorder.
COMPOUNDS AND METHODS FOR TREATING HIV INFECTIONS
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Paragraph 0371, (2015/04/21)
The present invention is directed to novel nanomolar and picomolar inhibitors of HIV reverse transcriptase, pharmaceutical compositions therefrom and methods for inhibiting reverse transcriptase and treating HIV infections, especially included drug resistant strains of HIV-1 and HIV-2 and/or secondary disease states and/or conditions which occur as a consequence of HIV infection.
Cu(I)-catalyzed efficient synthesis of 2'-triazolo-nucleoside conjugates
Mathur,Rana,Olsen,Parmar,Prasad
, p. 701 - 710 (2015/05/13)
A small library of thirty-two 2'-triazolyl uridine and 2'-triazolyl-5-methyluridine has been synthesized by Cu(I)-catalyzed condensation of 2'-azido-2'-deoxyuridine and 2'-azido-2'-deoxy-5-methyluridine with different alkynes and aryl propargyl ethers in almost quantitative yields. Triazolo-nucleoside conjugates, which can be evaluated for different biological activity for suitable drug development, were unambiguously identified on the basis of 1H NMR, 13C NMR, IR, and HRMS data analysis. These compounds have been synthesized for the first time and have not been reported in the literature earlier.
Microwave-assisted copper azide alkyne cycloaddition (CuAAC) reaction using D-glucose as a better alternative reductant
Kumar, Yogesh,Bahadur, Vijay,Singh, Anil K.,Parmar, Virinder S.,Singh, Brajendra K.
, p. 1893 - 1903 (2014/01/17)
D-Glucose has been established as a reducing agent for the copper azide alkyne cycloaddition (CuAAC) reactions. Efficacy of this new reductant has been established against various phenyl acetylenes (14 examples) and aryl azides (16 examples). All reaction
