In 2016,Marx, Isaac E.; Dineen, Thomas A.; Able, Jessica; Bode, Christiane; Bregman, Howard; Chu-Moyer, Margaret; DiMauro, Erin F.; Du, Bingfan; Foti, Robert S.; Fremeau, Robert T.; Gao, Hua; Gunaydin, Hakan; Hall, Brian E.; Huang, Liyue; Kornecook, Thomas; Kreiman, Charles R.; La, Daniel S.; Ligutti, Joseph; Lin, Min-Hwa Jasmine; Liu, Dong; McDermott, Jeff S.; Moyer, Bryan D.; Peterson, Emily A.; Roberts, Jonathan T.; Rose, Paul; Wang, Jean; Youngblood, Beth D.; Yu, Violeta; Weiss, Matthew M. published 《Sulfonamides as Selective NaV1.7 Inhibitors: Optimizing Potency and Pharmacokinetics to Enable in Vivo Target Engagement》.ACS Medicinal Chemistry Letters published the findings.Application of 847818-74-0 The information in the text is summarized as follows:
Human genetic evidence has identified the voltage-gated sodium channel NaV1.7 as an attractive target for the treatment of pain. The authors initially identified naphthalene sulfonamide 5-(2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)naphthalene-2-sulfonamide (compound 3) as a potent and selective inhibitor of NaV1.7. Optimization to reduce biliary clearance by balancing hydrophilicity and hydrophobicity (Log D) while maintaining NaV1.7 potency led to the identification of quinazoline 16 (AM-2099). Compound 16 demonstrated a favorable pharmacokinetic profile in rat and dog and demonstrated dose-dependent reduction of histamine-induced scratching bouts in a mouse behavioral model following oral dosing. After reading the article, we found that the author used 1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 847818-74-0Application of 847818-74-0)
1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole(cas: 847818-74-0) belongs to pyrazoles. Pyrazoles are commonly used scaffold molecules in drug discovery projects. The use of pyrazole derivatives is based on their analgesic, neuroleptic, anticonvulsant, monoamine oxidase inhibitory, anti-inflammatory, antipyretic, antiarrhythmic, sedative, muscle relaxant, antidiabetic and antibacterial activities. Application of 847818-74-0
Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics