1097921-02-2Relevant articles and documents
Discovery and Development of N-[4-(1-Cyclobutylpiperidin-4-yloxy)phenyl]-2-(morpholin-4-yl)acetamide Dihydrochloride (SUVN-G3031): A Novel, Potent, Selective, and Orally Active Histamine H3 Receptor Inverse Agonist with Robust Wake-Promoting Activity
Nirogi, Ramakrishna,Shinde, Anil,Mohammed, Abdul Rasheed,Badange, Rajesh Kumar,Reballi, Veena,Bandyala, Thrinath Reddy,Saraf, Sangram Keshari,Bojja, Kumar,Manchineella, Sravanthi,Achanta, Pramod Kumar,Kandukuri, Kiran Kumar,Subramanian, Ramkumar,Benade, Vijay,Palacharla, Raghava Choudary,Jayarajan, Pradeep,Pandey, Santoshkumar,Jasti, Venkat
, p. 1203 - 1217 (2019/02/24)
A series of chemical optimizations guided by in vitro affinity at a histamine H3 receptor (H3R), physicochemical properties, and pharmacokinetics in rats resulted in identification of N-[4-(1-cyclobutyl-piperidin-4-yloxy)phenyl]-2-(morpholin-4-yl)acetamide dihydrochloride (17v, SUVN-G3031) as a clinical candidate. Compound 17v is a potent (hH3R Ki = 8.73 nM) inverse agonist at H3R with selectivity over other 70 targets, Compound 17v has adequate oral exposures and favorable elimination half-lives both in rats and dogs. It demonstrated high receptor occupancy and marked wake-promoting effects with decreased rapid-eye-movement sleep in orexin-B saporin lesioned rats supporting its potential therapeutic utility in treating human sleep disorders. It had no effect on the locomotor activity at doses several fold higher than its efficacious dose. It is devoid of hERG and phospholipidosis issues. Phase-1 evaluation for safety, tolerability, and pharmacokinetics, and long-term safety studies in animals have been successfully completed without any concern for further development.
NOVEL COMPOUNDS 515
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Page/Page column 173-174, (2010/05/13)
There is provided novel pyrimidine derivatives of formula (I) or pharmaceutically acceptable salts thereof, processes for their preparation, pharmaceutical compositions containing them and their use in therapy