Decahydroisoquinoline derivatives as novel non-peptidic, potent and subtype-selective somatostatin sst3 receptor antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 5, 2010, Pages 1728-1734

  Troxler, Thomas ^a   Hurth, Konstanze ^a   Schuh, Karl Heinrich ^a   Schoeffter, Philippe ^a   Langenegger, Daniel ^a   Enz, Albert ^a   Hoyer, Daniel ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

Author keywords

GPCR; Non peptidic somatostatin receptor ligands; Somatostatin; Somatostatin sst3 receptor; Subtype selective sst3 receptor antagonists

Indexed keywords

(4,4A,8A) DECAHYDROISOQUINOLINE 4 CARBOXYLIC ACID; ACQ 090; DECAHYDROISOQUINOLINE DERIVATIVE; SOMATOSTATIN DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; BINDING AFFINITY; DRUG BLOOD LEVEL; DRUG POTENCY; DRUG SELECTIVITY; DRUG SYNTHESIS; ENANTIOMER; MOUSE; NONHUMAN; RAT; RODENT; STRUCTURE ACTIVITY RELATION;

ANIMALS; CRYSTALLOGRAPHY, X-RAY; HUMANS; ISOQUINOLINES; MOLECULAR CONFORMATION; PROTEIN ISOFORMS; RATS; RECEPTORS, SOMATOSTATIN; RECOMBINANT PROTEINS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

RODENTIA;

EID: 76749123830     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.01.063     Document Type: Article

References (38)

1. Brazeau P., Vale W., Burgus R., Ling N., Butcher M., Rivier J., and Guillemin R. Science 179 (1973) 77
2. Gerich J.E., Lovinger R., and Grodsky G.M. Endocrinology 96 (1975) 749
3. Johansson C., Wisen O., Efendic S., and Uvnas-Wallensten K. Digestion 22 (1981) 126
4. Weckbecker G., Lewis I., Albert R., Schmid H.A., Hoyer D., and Bruns C. Nat. Rev. Drug Disc. 2 (2003) 999
5. Viollet C., Lepousez G., Loudes C., Videau C., Simon A., and Epelbaum J. Mol. Cell. Endocrin. 286 (2008) 75
6. Vezzani A., and Hoyer D. Eur. J. Neurosci. 11 (1999) 3767
7. Dalm V., Hofland L.J., Mooy C.M., Waaijers M.A., Van Koetsveld P.M., Langerak A.W., Staal F.T.J., Van Der Lely A.J., Lamberts S.W.J., and Van Hagen M.P. J. Nucl. Med. 45 (2004) 8
8. Doran A.R., Rubinow D.R., Roy A., and Pickar D. Arch. Gen. Psych. 43 (1986) 365
9. Molchan S.E., Hill J.L., Martinez R.A., Lawlor B.A., Mellow A.M., Rubinow D.R., Bissette G., Nemeroff C.B., and Sunderland T. Psychoneuroendocrinology 18 (1993) 509
10. Fendt M., Koch M., and Schnitzler H.U. J. Neurosci. 16 (1996) 3097
11. Kluge C., Stoppel C., Szinyei C., Stork O., and Pape H.C. Learn. Mem. 15 (2008) 252
12. Thermos K., Bagnoli P., Epelbaum J., and Hoyer D. Pharmacol. Ther. 110 (2006) 455
13. Moneta D., Richichi C., Aliprandi M., Dournaud P., Dutar P., Billard J.M., Carlo A.S., Viollet C., Hannon J.P., Fehlmann D., Nunn C., Hoyer D., Epelbaum J., and Vezzani A. Eur. J. Neurosci. 16 (2002) 843
14. Epelbaum J., Guillou J.-L., Gastambide F., Hoyer D., Duron E., and Viollet C. Prog. Neurobiol. 89 (2009) 153
15. Videau C., Hochgeschwender U., Kreienkamp H.J., Brennan M.B., Viollet C., Richter D., and Epelbaum J. Naunyn-Schmiedeberg's Arch. Pharmacol. 367 (2003) 562
16. Reubi J.C., Waser B., Schaer J.-C., and Laissue J.A. Eur. J. Nucl. Med. 28 (2001) 836
17. Unger N., Serdiuk I., Sheu S.Y., Walz M.K., Schulz S., Schmid K.W., Mann K., and Petersenn S. Endocr. Res. 30 (2004) 931
18. Kang T.C., An S.J., Park S.K., Hwang I.K., Seo M.O., Kim H.S., Kang J.H., Kwon O.S., and Won M.H. Brain Res. 986 (2003) 91
19. Aourz N., Stragier B., Clinkers R., Michotte Y., and Smolders I. Epilepsia 50 (2009) 176
20. Engin E., and Treit D. Psychopharmacology 206 (2009) 281
21. Colucci R., Blandizzi C., Ghisu N., Florio T., and Del Tacca M. Br. J. Pharmacol. 155 (2008) 198
22. Thurieau, C. A.; Poitout, L. F.; Galcera, M.; Moinet, C. P.; Gordon, T. D.; Morgan, B. A.; Bigg, D. C. H.; Pommier, J. PCT Int. Appl. WO9964420A1, 1999; Chem. Abstr. 1999, 132, 35702.
23. Poitout L., Roubert P., Contour-Galcera M., Moinet C., Lannoy J., Pommier J., Plas P., Bigg D., and Thurieau C. J. Med. Chem. 44 (2001) 2990
24. Troxler, T. J.; Hurth, K.; Hoyer, D. PCT Int. Appl. WO2002081471A1, 2002; Chem. Abstr. 2002, 137, 295142.
25. Dobbelaar, P. H.; Du, W.; Guo, L.; Hagmann, W. K.; He, S.; Jian, T.; Liu, J.; Nargund, R. P.; Pasternak, A.; Shah, S. K.; Truong, Q. T.; Ye, Z.; Dellureficio, J.; Bakshi, R. PCT Int. Appl. WO2009011836A1, 2009, Chem. Abstr. 2009, 150, 168588.
26. Troxler T., Hoyer D., Langenegger D., Neumann P., Pfäffli P., Schoeffter P., Sorg D., Swoboda R., and Hurth K. Bioorg. Med. Chem. Lett. 17 (2007) 3983
27. Hurth K., Enz A., Floersheim P., Gentsch C., Hoyer D., Langenegger D., Neumann P., Pfäffli P., Sorg D., Swoboda R., Vassout A., and Troxler T. Bioorg. Med. Chem. Lett. 17 (2007) 3988
28. Troxler T., Enz A., Hoyer D., Langenegger D., Neumann P., Pfäffli P., Schoeffter P., and Hurth K. Bioorg. Med. Chem. Lett. 18 (2008) 979
29. Troxler T., Hurth K., Mattes H., Prashad M., Schoeffter P., Langenegger D., Enz A., and Hoyer D. Bioorg. Med. Chem. Lett. 19 (2009) 1305
30. 29 with a number of commercial or custom-made aldehydes, among the former being 3-benzo[1,3]dioxol-5-yl-2-methyl-propionaldehyde (Helional).
31. 1.
32. 33), followed by Pd catalyzed coupling with 5-bromo-isophthalic acid dimethyl ester as outlined in Scheme 3. Hydrolysis of the resulting methyl ester afforded an enantiomerically pure sample of 16 with known absolute configuration.
33. 3 ± SEM; 23a: 6.70 ± 0.05; 23b: 7.24 ± 0.03; 23c: 7.68 ± 0.04; 23d: 6.48 ± 0.13; 23e: 6.39 ± 0.04; 23f: 7.04 ± 0.15; 23g: 6.13 ± 0.03; 23h: 7.1 ± 0.17; 23i: 5.62 ± 0.06; 23j: 7.04 ± 0.04; 23k: 6.72 ± 0.04; 23l: 5.87 ± 0.06; 23m: 7.7 ± 0.1; 23n: 7.71 ± 0.06; 23o: 7.02 ± 0.05; 23p: 6.97 ± 0.07; 23q: 5.8 ± 0.13; 23r: 6.62 ± 0.16; 23s: 5.9 ± 0.08; 23t: 5.57 ± 0.1.
34. Klement I., Knochel P., Chau K., and Cahiez G. Tetrahedron Lett. 35 (1994) 1177
35. 3 ± SEM; 27a: 6.04 ± 0.07, 8.07 ± 0.12; 27b: 5.79 ± 0.02, 7.96 ± 0.04; 27c: 5.86 ± 0.03, 8.47 ± 0.02; 27d: 5.81 ± 0.05, 8.11 ± 0.03; 27e: 7.4 ± 0.02, 6.97 ± 0.02; 27f: 5.04 ± 0.01, 7.46 ± 0.01; 27g: 5.02 ± 0.06, 7.81 ± 0.07; 27h: 5.58 ± 0.05, 7.97 ± 0.06; 27i: 5.69 ± 0.01, 8.15 ± 0.02; 27j: 5.63 ± 0.04, 7.85 ± 0.06; 27k: 5.72 ± 0.04, 7.54 ± 0.04.
36. Hoyer D., Perez J., Schoeffter P., Langenegger D., Schüpbach E., Kaupmann K., Lübbert H., Bruns C., and Reubi J.C. Eur. J. Pharmacol. 289 (1995) 151
37. Hoyer D., Nunn C., Hannon J., Schoeffter P., Feuerbach D., Schuepbach E., Langenegger D., Bouhelal R., Hurth K., Neumann P., Troxler T., and Pfaeffli P. Neurosci. Lett. 361 (2004) 132
38. Baenziger M., Cercus J., Hirt H., Laumen K., Malan C., Spindler F., Struber F., and Troxler T. Tetrahedron: Asymmetry 14 (2003) 3469