Search | VHL Regional Portal

An evaluation of 3,4-methylenedioxy phenyl replacements in the aminopiperidine chromone class of MCHr1 antagonists.

Iyengar, Rajesh R; Lynch, John K; Mulhern, Mathew M; Judd, Andrew S; Freeman, Jennifer C; Gao, Ju; Souers, Andrew J; Zhao, Gang; Wodka, Dariusz; Doug Falls, H; Brodjian, Sevan; Dayton, Brian D; Reilly, Regina M; Swanson, Sue; Su, Zhi; Martin, Ruth L; Leitza, Sandra T; Houseman, Kathryn A; Diaz, Gilbert; Collins, Christine A; Sham, Hing L; Kym, Philip R.

Bioorg Med Chem Lett ; 17(4): 874-8, 2007 Feb 15.

Article in English | MEDLINE | ID: mdl-17234405

ABSTRACT

The optimization of potent MCHr1 antagonist 1 with respect to improving its in vitro profile by replacement of the 3,4-methylenedioxy phenyl (piperonyl) moiety led to the discovery of 19, a compound that showed excellent MCHr1 binding and functional potencies in addition to possessing superior hERG separation, CYP3A4 profile, and receptor cross-reactivity profiles.

Subject(s)

Piperidines/chemical synthesis , Piperidines/pharmacology , Receptors, Somatostatin/antagonists & inhibitors , Alkylation , Animals , Chemical Phenomena , Chemistry, Physical , Chromones , Cross Reactions , Cytochrome P-450 CYP3A , Cytochrome P-450 Enzyme Inhibitors , Dose-Response Relationship, Drug , ERG1 Potassium Channel , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Ether-A-Go-Go Potassium Channels/pharmacology , Heart Rate/drug effects , Heterocyclic Compounds/chemical synthesis , Heterocyclic Compounds/pharmacology , Humans , Mice , Structure-Activity Relationship

ABSTRACT

Subject(s)

SEND TO:

SELECTION OF CITATIONS

SEARCH DETAIL