On May 11, 2017, Gunaga, Prashantha; Lloyd, John; Mummadi, Somanadham; Banerjee, Abhisek; Dhondi, Naveen Kumar; Hennan, James; Subray, Veena; Jayaram, Ramya; Rajugowda, Nagendra; Umamaheshwar Reddy, Kommuri; Kumaraguru, Duraimurugan; Mandal, Umasankar; Beldona, Dasthagiri; Adisechen, Ashok Kumar; Yadav, Navnath; Warrier, Jayakumar; Johnson, James A.; Sale, Harinath; Putlur, Siva Prasad; Saxena, Ajay; Chimalakonda, Anjaneya; Mandlekar, Sandhya; Conder, MaryLee; Xing, Dezhi; Gupta, Arun Kumar; Gupta, Anuradha; Rampulla, Richard; Mathur, Arvind; Levesque, Paul; Wexler, Ruth R.; Finlay, Heather J. published an article.Name: Pyridine-3-sulfonic acid The title of the article was Selective IKur Inhibitors for the Potential Treatment of Atrial Fibrillation: Optimization of the Phenyl Quinazoline Series Leading to Clinical Candidate 5-[5-Phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl]pyridine-3-sulfonamide. And the article contained the following:
We have recently disclosed 5-phenyl-N-(pyridin-2-ylmethyl)-2-(pyrimidin-5-yl)quinazolin-4-amine (I) as a potent IKur current blocker with selectivity vs. hERG, Na and Ca channels and an acceptable preclin. PK profile. On further characterization in vivo, Compound I demonstrated an unacceptable level of brain penetration. In an effort to reduce the level of brain penetration while maintaining the overall profile, SAR was developed at the C2′ position for a series of close analogs by employing hydrogen bond donors. As a result, 5-(5-phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl)pyridine-3-sulfonamide (II) was identified as the lead compound in this series. Compound II showed robust effects in rabbit and canine pharmacodynamic models and an acceptable cross-species pharmacokinetic profile and was advanced as the clin. candidate. Further optimization of II to mitigate pH dependent absorption resulted in identification of the corresponding phosphoramide prodrug (29) with an improved solubility and pharmacokinetic profile. The experimental process involved the reaction of Pyridine-3-sulfonic acid(cas: 636-73-7).Name: Pyridine-3-sulfonic acid
The Article related to ph quinazoline sulfonamide synthesis pharmacokinetics brain potassium channel herg, pyridine sulfonamide antiarrhythmic atrial fibrillation, Pharmacology: Structure-Activity and other aspects.Name: Pyridine-3-sulfonic acid