Synthesis and NK1/NK2 binding activities of a series of diacyl-substituted 2-arylpiperazines

Bioorganic and Medicinal Chemistry Letters

Volumn 12, Issue 21, 2002, Pages 3161-3165

  Blythin, David J ^a   Chen, Xiao ^a   Piwinski, John J ^a   Shih, Neng Yang ^a   Shue, Ho Jane ^a   Anthes, John C ^a   McPhail, Andrew T ^b  

^a MERCK RESEARCH LABORATORIES   (United States)

^b DUKE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 (2 METHOXYBENZYLAMINO) 2 PHENYLPIPERIDINE; NEUROKININ 1 RECEPTOR; NEUROKININ 2 RECEPTOR; PIPERAZINE DERIVATIVE; TACHYKININ RECEPTOR ANTAGONIST;

ARTICLE; BINDING AFFINITY; CHIRAL CHROMATOGRAPHY; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG STRUCTURE; DRUG SYNTHESIS; ENANTIOMER; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION; X RAY CRYSTALLOGRAPHY;

AMINO ACIDS; ANIMALS; CRICETINAE; CRYSTALLOGRAPHY, X-RAY; GUINEA PIGS; MALE; MODELS, MOLECULAR; MOLECULAR CONFORMATION; PIPERAZINES; PIPERIDINES; RECEPTORS, NEUROKININ-1; RECEPTORS, NEUROKININ-2; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; TRACHEA; VAS DEFERENS;

EID: 0037020768     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(02)00645-5     Document Type: Article

References (20)

1. Presented at the 221st National Meeting of the American Chemical Society, San Diego, CA, April 1-5, 2001; MEDI 244.
2. Regoli D., Boudon A., Fauchere J.-L. Pharmacol. Rev. 46:1994;551.
3. Advenier C., Lagente V., Boichot E. Eur. Respir. J. 10:1997;1892.
4. Chapman R.W., Hey J.A., McLeod R., Minnicozzi M., Rizzo C.A. Drug News Perspect. 11:1998;480.
5. Gerspacher M., von Sprecher A. Drugs Future. 24:1999;883.
6. Reichard G.R., Ball Z.T., Aslanian R., Anthes J.C., Shih N.-Y., Piwinski J.J. Bioorg. Med. Chem. Lett. 10:2000;2329.
7. Ting P.C., Lee J.F., Anthes J.C., Shih N.-Y., Piwinski J. J. Bioorg. Med. Chem. Lett. 10:2000;2333.
8. Bernstein P.R., Aharony D., Albert J.S., Andisik D., Barthlow H.G., Bialecki R., Davenport T., Dedinas R.F., Dembofsky B.T., Koether G., Kosmider B.J., Kirkland K., Ohnmacht C.J., Potts W., Rumsey W.L., Shen L., Shenvi A., Sherwood S., Stollman D., Russell K. Bioorg. Med. Chem. Lett. 11:2001;2769.
9. Desai M.C., Lefkowitz S.L., Thadeio P.F., Longo K.P., Snider R.M. J. Med. Chem. 35:1992;4911.
10. After this project was begun a PCT application issued to Fujisawa Pharmaceutical Co., Ltd., Japan WO97/22597 covering certain 2-aryl-substituted piperazines as neurokinin antagonists. As far as we are aware, no literature publications have appeared describing their work.
11. Godek D.M., Rosen T.J. WO 91/18878. Chem. Abstr. 116:1992;106106.
12. Roderick W.R., Platte H.J., Pollard C.B. J. Med. Chem. 9:1966;181.
13. Cheng Y.C., Prusoff W.H. Biochem. Pharmacol. 22:1973;3099.
14. We thank Dr. K. McCormick for developing the resolution methodology.
15. Watson S.P. Br. J. Pharmacol. 80:1983;205.
16. Hall J.M., Morton I.K.M. Br. J. Pharmacol. 102:1991;511.
17. Maggi C.A., Patacchini R., Robero P., Mali A. Eur. J. Pharmacol. 166:1989;435.
18. Ellis J.L., Undem B.J., Kays J.S., Ghanekar S.V., Barthlow H.G., Buckner C.K. J. Pharmacol. Exper. Ther. 267:1993;95.
19. Furchgott R.F. Pharmacol. Rev. 7:1955;183.
20. w=0.058) over 1446 reflections with I2.0σ(I). Crystallographic data (excluding structure factors) have been deposited with the Cambridge Crystallographic Data Centre, deposition number CCDC 175702. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: +44-1223-336033; e-mail: deposit@ccdc.cam.ac.uk).