1254035-98-7Relevant academic research and scientific papers
Discovery of (3-(4-(2-Oxa-6-azaspiro[3.3]heptan-6-ylmethyl)phenoxy)azetidin-1-yl)(5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)methanone (AZD1979), a Melanin Concentrating Hormone Receptor 1 (MCHr1) Antagonist with Favorable Physicochemical Properties
Johansson, Anders,L?fberg, Christian,Antonsson, Madeleine,Von Unge, Sverker,Hayes, Martin A.,Judkins, Robert,Ploj, Karolina,Benthem, Lambertus,Lindén, Daniel,Brodin, Peter,Wennerberg, Marie,Fredenwall, Marléne,Li, Lanna,Persson, Joachim,Bergman, Rolf,Pettersen, Anna,Gennemark, Peter,Hogner, Anders
supporting information, p. 2497 - 2511 (2016/04/10)
A novel series of melanin concentrating hormone receptor 1 (MCHr1) antagonists were the starting point for a drug discovery program that culminated in the discovery of 103 (AZD1979). The lead optimization program was conducted with a focus on reducing lipophilicity and understanding the physicochemical properties governing CNS exposure and undesired off-target pharmacology such as hERG interactions. An integrated approach was taken where the key assay was ex vivo receptor occupancy in mice. The candidate compound 103 displayed appropriate lipophilicity for a CNS indication and showed excellent permeability with no efflux. Preclinical GLP toxicology and safety pharmacology studies were without major findings and 103 was taken into clinical trials.
The Development of a Manufacturing Route to an MCHr1 Antagonist
Golden, Michael,Legg, Danny,Milne, David,Arun Bharadwaj,Deepthi,Gopal, Madan,Dokka, Nagaraju,Nambiar, Sudhir,Ramachandra, Puranik,Santhosh,Sharma, Parhalad,Sridharan,Sulur, Manjunatha,Linderberg, Mats,Nilsson, Anders,Sohlberg, Roger,Kremers, John,Oliver, Samuel,Patra, Debasis
, p. 675 - 682 (2016/04/01)
Process development work to provide an efficient manufacturing route to a MCHr1 antagonist is presented herewith. Features of this development work include a scalable manufacturing route to the useful 6-oxa-2-azaspiro[3.3]heptane building block and the use of a (soluble) alternative to sodium triacetoxyborohydride.
THERAPEUTIC AGENTS 713
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Page/Page column 42, (2010/11/17)
Disclosed herein are compounds of Formula (I) in which R1, R2, R3, R4, R5, A, X, Y are as described in the specification, their use in pharmaceutical compositions and in methods of treatment or prophylaxis of a melanin-concentrating hormone related disease or condition.
