Design and syntheses of melanocortin subtype-4 receptor agonists: Evolution of the pyridazinone archetype

Bioorganic and Medicinal Chemistry Letters

Volumn 13, Issue 24, 2003, Pages 4431-4435

  Ujjainwalla, Feroze ^a   Warner, Daniel ^a   Walsh, Thomas F ^a   Wyvratt, Matthew J ^a   Zhou, Changyou ^a   Yang, Lihu ^a   Kalyani, Rubana N ^a   MacNeil, Tanya ^a   Van Der Ploeg, Lex H T ^a   Rosenblum, Charles I ^a   Tang, Rui ^a   Vongs, Aurawan ^a   Weinberg, David H ^a   Goulet, Mark T ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HORMONE RECEPTOR STIMULATING AGENT; MELANOCORTIN 4 RECEPTOR; MELANOCORTIN 4 RECEPTOR STIMULATING AGENT; MELANOCORTIN RECEPTOR AFFECTING AGENT; PYRIDAZINONE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DRUG DESIGN; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; IC 50; PROTON TRANSPORT; STEREOCHEMISTRY;

EID: 0344927055     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2003.09.026     Document Type: Article

References (14)

1. (a) . For recent reviews on the Melanocortin system see: Zimanyi I.A., Pelleymounter M.A. Curr. Pharm. Des. 9:2003;627 (b) Gantz I., Fong T.M. Am. J. Physiol. Endocrinol. Metab. 284:2003;E468 (c) MacNeil D.J., Howard A.D., Guan X., Fong T.M., Nargund R., Bednarek M.A., Goulet M.T., Weinberg D.H., Strack A.M., Marsh D.J., Chen H.Y., Shen C.-P., Chen A.S., Rosenblum C.I., MacNeil T., Tota M., MacIntyre D.E., Van der Ploeg L.H.T. Eur. J. Pharmacol. 440:2002;141 (d) Wikberg J.E.S. Exp. Opin. Ther. Pat. 11:2001;61 (e) Anderson P.M., Boman A., Seifert E., Skottner A., Lundstedt T. Exp. Opin. Ther. Pat. 11:2001;1583 (f) Wikberg J.E.S. Eur. J. Pharmacol. 375:1999;295.
2. Lu D., Willard D., Patel I.R., Kadwell S., Overton L., Kost T., Luther M., Chen W., Woychik R.P., Wilkison W.O., Cone R.D. Nature. 371:1994;799.
3. For the first description of an agouti gene, see: Woychik, R. P. US 6080550, June 27, 2000.
4. Huszar D., Lynch C.A., Fairchild-Huntress V., Dunmore J.H., Fang Q., Berkemeier L.R., Gu W., Kesterson R.A., Boston B.A., Cone R.D., Smith F.J., Campfield L.A., Burn P., Lee F. Cell. 88:1997;131.
5. (a) Gu W., Tu Z., Kleyn P.W., Kissebah A., Duprat L., Lee J., Chin W., Maruti S., Deng N., Fisher S.L., Franco L.S., Burn P., Yagaloff K.A., Nathan J., Heymsfield S., Albu J., Pi-Sunyer F.X., Allison D.B. Diabetes. 48:1999;635 (b) Hinney A., Schmidt A., Nottebom K., Heibult O., Becker I., Ziegler A., Gerber G., Sina M., Gorg T., Mayer H., Siegfried W., Fichter M., Remschmidt H., Hebebrand J. J. Clin. Endocrin. Metab. 84:1999;1483.
6. Sebhat I.K., Martin W.J., Zhixiong Y., Barakat K., Mosley R.T., Johnston D.B.R., Bakshi R., Palucki B., Weinberg D.H., MacNeil T., Kalyani R.N., Tang R., Stearns R.A., Miller R., Tamvakopoulos C., Strack A., McGowan E., Cashen D.E., Drisko J.E., Hom G.J., Howard A.D., MacIntyre D.E., Van der Ploeg L.H.T., Patchett A.A., Nargund R.P. J. Med. Chem. 45:2002;4589.
7. Preliminary SAR studies on this lead class were conducted by C. Zhou, Yanping Pan and L. Yang, unpublished results.
8. Bochis, R. J.; Kotliar, A.; Parsons, W. H.; Rupprecht, K. M. US 5670504, Sept. 23, 1997.
9. Pappo R., Allen D.S. Jr., Lemieux R.U., Johnson W.S. J. Org. Chem. 21:1956;478.
10. Viaud M.C., Rollin P. Synthesis. 1990;130.
11. Chakravarty, P. K.; Chen, M. H.; Nargund, R. P; Patchett, A. A.; Tata, J. R.; Wu, M. T.; Yang, L. US 5804578, Sept. 8, 1998.
12. 50 is defined as the inflection point of the cAMP dose-response curve for any given compound or the cAMP accumulation (relative to α-MSH) observed at the highest compound concentration tested. %Max is the percentage of cAMP accumulation at 10 μM of compound relative to α-MSH. For a detailed description of the assay protocols see: Bednarek M.A., MacNeil T., Kalyani R.N., Tang R., van der Ploeg L.H.T., Weinberg D.H. J. Med. Chem. 44:2001;3665 (b) Bednarek M.A., Silva M.V., Arison B., MacNeil T., Kalyani R.N., Huang R.-R. C., Weinberg D.H. Peptides. 20:1999;401.
13. 50 is defined as the inflection point of the cAMP dose-response curve for any given compound or the cAMP accumulation (relative to α-MSH) observed at the highest compound concentration tested. %Max is the percentage of cAMP accumulation at 10 μM of compound relative to α-MSH. For a detailed description of the assay protocols see: Bednarek M.A., MacNeil T., Kalyani R.N., Tang R., van der Ploeg L.H.T., Weinberg D.H. J. Med. Chem. 44:2001;3665 (b) Bednarek M.A., Silva M.V., Arison B., MacNeil T., Kalyani R.N., Huang R.-R. C., Weinberg D.H. Peptides. 20:1999;401.
14. Ujjainwalla, F.; Warner, D., unpublished results.