- Design, synthesis and biological evaluation of quinazoline derivatives as potent and selective FGFR4 inhibitors
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Aberrant activation of the fibroblast growth factor 19-fibroblast growth factor receptor 4 (FGF19-FGFR4) signaling pathway has been proved to promote hepatocellular carcinoma (HCC) proliferation. It is assumed that the first FGFR4 inhibitor BLU9931 did no
- Pan, Chenghao,Nie, Wenwen,Wang, Jiao,Du, Jiamin,Pan, Zhichao,Gao, Jian,Lu, Yang,Che, Jinxin,Zhu, Hong,Dai, Haibin,Chen, Binhui,He, Qiaojun,Dong, Xiaowu
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- Pyrrole inhibitors of S-nitrosoglutathione reductase as therapeutic agents
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The present invention is directed to inhibitors of S-nitrosoglutathione reductase (GSNOR), pharmaceutical compositions comprising such GSNOR inhibitors, and methods of making and using the same.
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- Structure-activity relationship of pyrrole based S-nitrosoglutathione reductase inhibitors: Carboxamide modification
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The enzyme S-nitrosoglutathione reductase (GSNOR) is a member of the alcohol dehydrogenase family (ADH) that regulates the levels of S-nitrosothiols (SNOs) through catabolism of S-nitrosoglutathione (GSNO). GSNO and SNOs are implicated in the pathogenesis of many diseases including those in respiratory, gastrointestinal, and cardiovascular systems. The pyrrole based N6022 was recently identified as a potent, selective, reversible, and efficacious GSNOR inhibitor which is currently in clinical development for acute asthma. We describe here the synthesis and structure-activity relationships (SAR) of novel pyrrole based analogs of N6022 focusing on carboxamide modifications on the pendant N-phenyl moiety. We have identified potent and novel GSNOR inhibitors that demonstrate efficacy in an ovalbumin (OVA) induced asthma model in mice.
- Sun, Xicheng,Qiu, Jian,Strong, Sarah A.,Green, Louis S.,Wasley, Jan W.F.,Blonder, Joan P.,Colagiovanni, Dorothy B.,Stout, Adam M.,Mutka, Sarah C.,Richards, Jane P.,Rosenthal, Gary J.
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p. 2338 - 2342
(2012/04/18)
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- BENZOPHENONES AS INHIBITORS OF REVERSE TRANSCRIPTASE
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The present invention includes benzophenone compounds (I) which are useful in the treatment of HIV infections.
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Page/Page column 9; 20
(2010/11/08)
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- Structure-activity relationship studies of novel benzophenones leading to the discovery of a potent, next generation HIV nonnucleoside reverse transcriptase inhibitor
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Despite the progress of the past two decades, there is still considerable need for safe, efficacious drugs that target human immunodeficiency virus (HIV). This is particularly true for the growing number of patients infected with virus resistant to currently approved HIV drugs. Our high throughput screening effort identified a benzophenone template as a potential nonnucleoside reverse transcriptase inhibitor (NNRTI). This manuscript describes our extensive exploration of the benzophenone structure-activity relationships, which culminated in the identification of several compounds with very potent inhibition of both wild type and clinically relevant NNRTI-resistant mutant strains of HIV. These potent inhibitors include 70h (GW678248), which has in vitro antiviral assay IC50 values of 0.5 nM against wild-type HIV, 1 nM against the K103N mutant associated with clinical resistance to efavirenz, and 0.7 nM against the Y181C mutant associated with clinical resistance to nevirapine. Compound 70h has also demonstrated relatively low clearance in intravenous pharmacokinetic studies in three species, and it is the active component of a drug candidate which has progressed to phase 2 clinical studies.
- Romines, Karen R.,Freeman, George A.,Schaller, Lee T.,Cowan, Jill R.,Gonzales, Steve S.,Tidwell, Jeffrey H.,Andrews III, Clarence W.,Stammers, David K.,Hazen, Richard J.,Ferris, Robert G.,Short, Steven A.,Chan, Joseph H.,Boone, Lawrence R.
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p. 727 - 739
(2007/10/03)
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- Novel Benzophenones as Non-nucleoside Reverse Transcriptase Inhibitors of HIV-1
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GW4511, GW4751, and GW3011 showed IC50 values ≤2 nM against wild type HIV-1 and 10 nM against 16 mutants. They were particularly potent against NNRTI-resistant viruses containing Y181C-, K103N-, and K103N-based double mutations, which account for a significant proportion of the clinical failure of the three currently marketed NNRTIs. The antiviral data together with the favorable pharmacokinetic data of GW4511 suggested that these benzophenones possess attributes of a new NNRTI drug candidate.
- Chan, Joseph H.,Freeman, George A.,Tidwell, Jeffrey H.,Romines, Karen R.,Schaller, Lee T.,Cowan, Jill R.,Gonzales, Steve S.,Lowell, Gina S.,Andrews III,Reynolds, David J.,St. Clair, Marty,Hazen, Richard J.,Ferris, Rob G.,Creech, Katrina L.,Roberts, Grace B.,Short, Steven A.,Weaver, Kurt,Koszalka, George W.,Boone, Lawrence R.
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p. 1175 - 1182
(2007/10/03)
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- Benzenesulfonamide-derivatives and their use as medicaments
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Compounds of formula (I), pharmaceutically acceptable salts or in vivo hydrolysable esters thereof, wherein: Ring X is phenyl or a six membered heteroaryl ring containing one or two ring nitrogens where said nitrogens are optionally oxidised to form the N
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- Synthesis of substituted 2-(4-amino phenyl sulphonamide)thiazoles
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Various 2-(4-amino phenyl sulphonamide) thiazoles (5a-g, 6a-g) have been prepared in good yield by condensation of 5-ethoxy-4-methyl/4-phenyl 2-amino thiazole (1a and 1b) with p-acetamido benzene sulphonyl chloride derivative (2) in pyridine-acetic anhydr
- Gupta,Phull, Manjinder Singh
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p. 967 - 969
(2007/10/03)
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