Dyck, Brian; Grigoriadis, Dimitri E.; Gross, Raymond S.; Guo, Zhiqiang; Marinkovic, Dragan; McCarthy, James R.; Moorjani, Manisha; Regan, Collin F.; Saunders, John; Schwaebe, Michael K.; Szabo, Tomas; Williams, John P.; Zhang, Xiaohu; Bozigian, Haig; Chen, Ta Kung published the artcile< Potent, Orally Active Corticotropin-Releasing Factor Receptor-1 Antagonists Containing a Tricyclic Pyrrolopyridine or Pyrazolopyridine Core>, Application of C9H9Cl2NO2, the main research area is oral CRF1 receptor antagonist tricyclic pyrrolopyridine pyrazolopyridine core preparation.
Two new classes of tricyclic-based corticotropin-releasing factor (CRF1) receptor-1 antagonists were designed by constraining known 1H-pyrrolo[2,3-b]pyridine and 1H-pyrazolo[3,4-b]pyridine ligands. Pyrrole- and pyrazole-based mols. 19g and 22a, resp., were discovered that potently bind the recombinant CRF1 receptor (Ki = 3.5, 2.9 nM) and inhibit adrenocorticotropic hormone (ACTH) release from rat pituitary cell culture (IC50 = 14, 6.8 nM). These compounds show good oral bioavailability (F = 24%, 7.0%) and serum half-lives in rats (t1/2 = 6.3, 12 h) and penetrate the rat brain ([brain]/[plasma] = 0.27, 0.52) but tend toward large volumes of distribution (VD = 38, 44 L kg-1) and rapid clearances (CL = 70, 43 mL min-1 kg-1). When given orally, both the pyrazole and the pyrrole leads dose-dependently inhibit stress-induced ACTH release in vivo. ACTH reductions of 84-86% were observed for 30 mg kg-1 doses.
Journal of Medicinal Chemistry published new progress about Blood-brain barrier (penetration). 86129-63-7 belongs to class pyridine-derivatives, and the molecular formula is C9H9Cl2NO2, Application of C9H9Cl2NO2.