2-Aminomethyl piperidines as novel urotensin-II receptor antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 9, 2008, Pages 2860-2864

  Jin, Jian ^a   Wang, Yonghui ^a   Wang, Feng ^a   Shi, Dongchuan ^a   Erhard, Karl F ^a   Wu, Zining ^a   Guida, Brian F ^a   Lawrence, Sarah K ^a   Behm, David J ^a   Disa, Jyoti ^a   Vaidya, Kalindi S ^a   Evans, Christopher ^a   McMillan, Lynette J ^a   Rivero, Ralph A ^a   Neeb, Michael J ^a   Douglas, Stephen A ^a  

^a GLAXOSMITHKLINE   (United States)

Author keywords

2 aminomethyl piperidine; Broad cross species activity; Competitive, reversible, and functional antagonist; Urotensin II receptor antagonist; UT antagonist

Indexed keywords

2 AMINOMETHYLPIPERIDINE DERIVATIVE; BENZOTHIOPHENE DERIVATIVE; CYTOCHROME P450; PIPERIDINE; PROLINE DERIVATIVE; RECEPTOR BLOCKING AGENT; UROTENSIN II;

ANIMAL EXPERIMENT; ANIMAL TISSUE; AORTA; ARTICLE; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG HALF LIFE; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; FEMORAL ARTERY; IC 50; NONHUMAN; RAT; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION;

BINDING SITES; HUMANS; METHYLAMINES; MODELS, CHEMICAL; PIPERIDINES; RECEPTORS, G-PROTEIN-COUPLED; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; VASOCONSTRICTOR AGENTS;

EID: 42949164575     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.03.078     Document Type: Article

References (35)

1. Ames R.S., Sarau H.M., Chambers J.K., Willette R.N., Aiyar N.V., Romanic A.M., Louden C.S., Foley J.J., Sauermelch C.F., Coatney R.W., Ao Z., Disa J., Holmes S.D., Stadel J.M., Martin J.D., Liu W.S., Glover G.I., Wilson S., McNulty D.E., Ellis C.E., Elshourbagy N.A., Shabon U., Trill J.J., Hay D.W., Ohlstein E.H., Bergsma D.J., and Douglas S.A. Nature 401 (1999) 282
2. Douglas S.A., Dhanak D., and Johns D.G. Trends Pharmacol. Sci. 25 (2004) 76
3. Matsushita M., Shichiri M., Imai T., Iwashina M., Tanaka H., Takasu N., and Hirata Y. J. Hypertens. 19 (2001) 2185
4. Cheung B.M., Leung R., Man Y.B., and Wong L.Y. J. Hypertens. 22 (2004) 1341
5. Russell F.D., Meyers D., Galbraith A.J., Bett N., Toth I., Kearns P., and Molenaar P. Am. J. Physiol. 285 (2003) H1576
6. Douglas S.A., Tayara L., Ohlstein E.H., Halawa N., and Giaid A. Lancet 359 (2002) 1990
7. Ng L.L., Loke I., O'Brien R.J., Squire I.B., and Davies J.E. Circulation 106 (2002) 2877
8. Richards A.M., Nicholls M.G., Lainchbury J.G., Fisher S., and Yandle T.G. Lancet 360 (2002) 545
9. Lapp H., Boerrigter G., Costello-Boerrigter L.C., Jaekel K., Scheffold T., Krakau I., Schramm M., Guelker H., and Stasch J.P. Int. J. Cardiol. 94 (2004) 93
10. Bousette N., Patel L., Douglas S.A., Ohlstein E.H., and Giaid A. Atherosclerosis 176 (2004) 117
11. Maguire J.J., Kuc R.E., Wiley K.E., Kleinz M.J., and Davenport A.P. Peptides 25 (2004) 1767
12. Totsune K., Takahashi K., Arihara Z., Sone M., Satoh F., Ito S., Kimura Y., Sasano H., and Murakami O. Lancet 358 (2001) 810
13. Shenouda A., Douglas S.A., Ohlstein E.H., and Giaid A. J. Histochem. Cytochem. 50 (2002) 885
14. Langham R.G., Gow R., Thomson N.M., Dowling J.K., and Gilbert R.E. Am. J. Kidney Dis. 44 (2004) 826
15. Totsune K., Takahashi K., Arihara Z., Sone M., Satoh F., Ito S., and Murakami O. Clin. Sci. 104 (2003) 1
16. Wenyi Z., Suzuki S., Hirai M., Hinokio Y., Tanizawa Y., Matsutani A., Satoh J., and Oka Y. Diabetologi 46 (2003) 972
17. Flohr S., Kurz M., Kostenis E., Brkovich A., Fournier A., and Klabunde T. J. Med. Chem. 45 (2002) 1799
18. Croston G.E., Olsson R., Currier E.A., Burstein E.S., Weiner D., Nash N., Severance D., Allenmark S.G., Thunberg L., Ma J., Mohell N., O'Dowd B., Brann M.R., and Hacksell U. J. Med. Chem. 45 (2002) 4950
19. Clozel M., Binkert C., Birker-Robaczewska M., Boukhadra C., Ding S., Fischli W., Hess P., Mathys B., Morrison K., Muller C., Muller C., Nayler O., Qiu C., Rey M., Scherz M.W., Velker J., Weller T., Xi J., and Ziltener P. J. Pharma. Exp. Ther. 311 (2004) 204
20. Jin J., Dhanak D., Knight S.D., Widdowson K., Aiyar N., Naselsky D., Sarau H.M., Foley J.J., Schmidt D.B., Bennett C.D., Wang B., Warren G.L., Moore M.L., Keenan R.M., Rivero R.A., and Douglas S.A. Bioorg. Med. Chem. Lett. 15 (2005) 3229
21. Douglas S.A., Behm D.J., Aiyar N.V., Naselsky D., Disa J., Brooks D.P., Ohlstein E.H., Gleason J.G., Sarau H.M., Foley J.J., Buckley P.T., Schmidt D.B., Wixted W.E., Widdowson K., Riley G., Jin J., Gallagher T.F., Schmidt S.J., Ridgers L., Christmann L.T., Keenan R.M., Knight S.D., and Dhanak D. Br. J. Pharmacol. 145 (2005) 620
22. Lehmann F., Pettersen A., Currier E.A., Sherbukhin V., Olsson R., Hacksell U., and Luthman K. J. Med. Chem. 49 (2006) 2232
23. Luci D.K., Ghosh S., Smith C.E., Qi J., Wang Y., Haertlein B., Parry T.J., Li J., Almond H.R., Minor L.K., Damiano B.P., Kinney W.A., Maryanoff B.E., and Lawson E.C. Bioorg. Med. Chem. Lett. 17 (2007) 6489
24. For a recent review, see:. Jin J., and Douglas S.A. Expert Opin. Ther. Patents 16 (2006) 467
25. i-mobilization assay details, see Ref. 9e.
26. The chiral centers in the structures shown in the paper are racemic except the ones in 1a, 1b, 11a and 11b.
27. The radioligand binding assay was used as the primary assay to generate SAR.
28. 1H NMR.
29. Sakamoto T., Kaneda S., Nishimura S., and Yamanaka H. Chem. Pharm. Bull. 3 (1985) 565
30. Diamine 6d was produced as an over reduction by-product in the hydrogenation step from conversion of 5a to 6a.
31. Compounds 7e and 7f were prepared from the corresponding commercially available amino acids in the same way as the preparation of 3a from 4 in Scheme 1.
32. T 3.3 and 5.1 min.
33. Stereochemistry was assigned by Vibrational Circular Dichroism (VCD) analysis of both enantiomers.
34. For cat and rat UT receptor radioligand binding and rat isolated aorta contractile assay details, see Ref. 9e.
35. For cat isolated femoral artery assay details, see:. Behm D.J., Stankus G., Doe C.P., Willette R.N., Sarau H.M., Foley J.J., Schmidt D.B., Nuthulaganti P., Fornwald J.A., Ames R.S., Lambert D.G., Calo' G., Camarda V., Aiyar N.V., and Douglas S.A. Br. J. Pharmacol. 148 (2006) 173