- Design, synthesis, and structure-activity relationship studies of novel fused heterocycles-linked triazoles with good activity and water solubility
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Triazoles with fused-heterocycle nuclei were designed and evaluated for their in vitro activity on the basis of the binding mode of albaconazole using molecular docking, along with SAR of antifungal triazoles. Tetrahydro-[1,2,4] triazolo[1,5-a]pyrazine and tetrahydro-thiazolo[5,4-c]pyridine nuclei were preferable to the other four fused-heterocycle nuclei investigated. Potent in vitro activity, broad spectrum and better water solubility were attained when triazoles containing nitrogen aromatic heterocycles were attached to these two nuclei. The most potent compounds 27aa and 45x, with low hERG inhibition and hepatocyte toxicity, both exhibited excellent activity against Candida, Cryptococcus, and Aspergillus spp., as well as selected fluconazole-resistant strains. A high water-soluble compound 58 (the disulfate salt of 45x) displayed unsatisfactory in vivo activity because of its poor PK profiles. Mice infected with C.alb. SC5314 and C.alb. 103 (fluconazole-resistant strain) and administered with 27aa displayed significantly improved survival rates. 27aa also showed favorable pharmacokinetic (PK) profiles.
- Cao, Xufeng,Sun, Zhaoshuan,Cao, Yongbing,Wang, Ruilian,Cai, Tongkai,Chu, Wenjing,Hu, Wenhao,Yang, Yushe
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p. 3687 - 3706
(2014/05/20)
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- SUBSTITUTED SULFONAMIDE DERIVATIVES
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The invention relates to substituted sulfonamide derivatives of the general formula (I'); processes for their preparation, medicaments containing these compounds, and the use of substituted sulfonamide derivatives for the preparation of medicaments
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Page/Page column 108; 109
(2009/08/16)
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- SUBSTITUTED SULFONAMIDE COMPOUNDS
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Substituted sulfonamide derivatives, a process for their preparation, pharmaceutical compositions containing these compounds, and to the use of substituted sulfonamide derivatives in the treatment or inhibition of pain and/or various disorders or disease states.
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Page/Page column 68
(2008/12/06)
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- Design, synthesis, and biological evaluation of triazolopiperazine-based β-amino amides as potent, orally active dipeptidyl peptidase IV (DPP-4) inhibitors
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Various β-amino amides containing triazolopiperazine heterocycles have been prepared and evaluated as potent, selective, orally active dipeptidyl peptidase IV (DPP-4) inhibitors. These compounds display excellent oral bioavailability and good overall phar
- Kowalchick, Jennifer E.,Leiting, Barbara,Pryor, KellyAnn D.,Marsilio, Frank,Wu, Joseph K.,He, Huaibing,Lyons, Kathryn A.,Eiermann, George J.,Petrov, Aleksandr,Scapin, Giovanna,Patel, Reshma A.,Thornberry, Nancy A.,Weber, Ann E.,Kim, Dooseop
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p. 5934 - 5939
(2008/09/20)
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- AMINOCYCLOHEXANES AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
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The present invention is directed to novel substituted aminocyclohexanes which are inhibitors of the dipeptidyl peptidase-IV enzyme ("DPP-IV inhibitors") and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.
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Page/Page column 46
(2008/06/13)
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