Aryloxypyrazines as highly selective antagonists of Oxytocin

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 10, 2009, Pages 2634-2636

  Brown, Alan ^a   Ellis, Dave ^a   Pearce, David ^a   Ralph, Michael ^a   Sciammetta, Nunzio ^a  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United Kingdom)

Author keywords

Antagonist; Oxytocin

Indexed keywords

OXYTOCIN; OXYTOCIN ANTAGONIST; PYRAZINE DERIVATIVE; VASOPRESSIN V1A RECEPTOR;

ARTICLE; DRUG DESIGN; DRUG POTENCY; DRUG SELECTIVITY; DRUG STRUCTURE; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS;

OXYTOCIN; PYRAZINES; RECEPTORS, VASOPRESSIN;

EID: 65349165258     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.03.160     Document Type: Article

References (8)

1. Gullam J.E., Chatterjee J., and Thornton S. Drug Discovery Today 2 (2005) 47
2. Tiwari A., Nanda K., and Chugh A. Expert Opin. Invest. Drugs 14 (2005) 1359
3. See, for example, WO 2005028452 and the references therein.
4. Brown A., Brown L., Ellis D., Puhalo N., and Smith C.R. Bioorg. Med. Chem. Lett. 18 (2008) 4278
5. (a) Conformational analysis was carried out using in-house software. Local minimum conformations of potential targets such as 2 were overlapped with compound 1. (b) The minimized conformation of compound 1 illustrated was, in fact, extremely close to that observed in the small molecule X-ray of this compound.
6. All biological data reported herein represents functional antagonism, as measured against the corresponding cloned human receptor in a cell based β lactamase assay, using technology licensed from Rhoto Pharmaceuticals.
7. See Ref. 4 and the references therein for a discussion on heavy atom ligand efficiency and lipophilicity versus drug-like properties for compounds such as 1.
8. Abbreviations used in Scheme 1 as follows: NMM-N-methylmorpholine; PTSA-p-toluenesulphonic acid; NMP-N-methyl-2-pyrrolidinone.