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Zhang Y.-K.,Anacor Pharmaceuticals Inc. | Plattner J.J.,Anacor Pharmaceuticals Inc. | Easom E.E.,Anacor Pharmaceuticals Inc. | Zhou Y.,Anacor Pharmaceuticals Inc. | And 10 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2015

A novel series of isoxazoline benzoxaborole small molecules was designed and synthesized for a structure-activity relationship (SAR) investigation to assess the ectoparasiticide activity against ticks and fleas. The study identified an orally bioavailable molecule, (S)-3,3-dimethyl-5-(5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)benzo[c][1,2]oxaborol-1(3H)-ol (38, AN8030), which was long lasting in dogs (t1/2 = 22 days). Compound 38 demonstrated 97.6% therapeutic effectiveness within 24 h of treatment, with residual efficacy of 95.3% against American dog ticks (Dermacentor variabilis) on day 30% and 100% against cat fleas (Ctenocephalides felis) on day 32 after a single oral dose at 50 mg/kg in dogs. © 2015 Elsevier Ltd. All rights reserved. Source


Li X.,Anacor Pharmaceuticals Inc. | Zhang S.,Anacor Pharmaceuticals Inc. | Zhang Y.-K.,Anacor Pharmaceuticals Inc. | Liu Y.,Anacor Pharmaceuticals Inc. | And 20 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2011

We have synthesized and evaluated a new series of acyclic P4-benzoxaborole-based HCV NS3 protease inhibitors. Structure-activity relationships were investigated, leading to the identification of compounds 5g and 17 with low nanomolar potency in the enzymatic and cell-based replicon assay. The linker-truncated compound 5j was found to exhibit improved absorption and oral bioavailability in rats, suggesting that further reduction of molecular weight and polar surface area could result in improved drug-like properties of this novel series. © 2011 Elsevier Ltd. All rights reserved. Source


Li X.,Anacor Pharmaceuticals Inc. | Zhang Y.-K.,Anacor Pharmaceuticals Inc. | Liu Y.,Anacor Pharmaceuticals Inc. | Zhang S.,Anacor Pharmaceuticals Inc. | And 19 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2010

HCV NS3/4A serine protease is essential for the replication of the HCV virus and has been a clinically validated target. A series of HCV NS3/4A protease inhibitors containing a novel acylsulfamoyl benzoxaborole moiety at the P1′ region was synthesized and evaluated. The resulting P1-P3 and P2-P4 macrocyclic inhibitors exhibited sub-nanomolar potency in the enzymatic assay and low nanomolar activity in the cell-based replicon assay. The in vivo PK evaluations of selected compounds are also described. © 2010 Elsevier Ltd. All rights reserved. Source


Ding C.Z.,Anacor Pharmaceuticals Inc. | Zhang Y.-K.,Anacor Pharmaceuticals Inc. | Li X.,Anacor Pharmaceuticals Inc. | Liu Y.,Anacor Pharmaceuticals Inc. | And 17 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2010

We disclose here a series of P4-benzoxaborole-substituted macrocyclic HCV protease inhibitors. These inhibitors are potent against HCV NS3 protease, their anti-HCV replicon potencies are largely impacted by substitutions on benzoxaborole ring system and P2 groups. P2 2-thiazole-isoquinoline provides best replicon potency. The in vitro SAR studies and in vivo PK evaluations of selected compounds are described herein. © 2010 Elsevier Ltd. All rights reserved. Source


Li X.,Anacor Pharmaceuticals Inc. | Zhang Y.-K.,Anacor Pharmaceuticals Inc. | Liu Y.,Anacor Pharmaceuticals Inc. | Ding C.Z.,Anacor Pharmaceuticals Inc. | And 29 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2010

We have designed and synthesized a novel series of α-amino cyclic boronates and incorporated them successfully in several acyclic templates at the P1 position. These compounds are inhibitors of the HCV NS3 serine protease, and structural studies show that they inhibit the NS3 protease by trapping the Ser-139 hydroxyl group in the active site. Synthetic methodologies and SARs of this series of compounds are described. © 2010 Elsevier Ltd. Source

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