Characterization of the binding site of the histamine H3 receptor. 2. Synthesis, in vitro pharmacology, and QSAR of a series of monosubstituted benzyl analogues of thioperamide

Journal of Medicinal Chemistry

Volumn 43, Issue 9, 2000, Pages 1754-1761

  Windhorst, Albert D ^a   Timmerman, Henk ^a   Worthington, Edward A ^a   Bijloo, Greetje J ^a   Nederkoorn, Paul H J ^a   Menge, Wiro M P B ^a   Leurs, Rob ^a   Herscheid, Jacobus D M ^a  

^a VU UNIVERSITY AMSTERDAM   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

HISTAMINE H3 RECEPTOR; HISTAMINE H3 RECEPTOR ANTAGONIST; N (2 BROMOBENZYL) N' [4 (1H IMIDAZOL 4 YL)PIPERIDINYL]THIOUREA HEMIFUMARATE; N (2 CHLOROBENZYL) N' [4 (1H IMIDAZOL 4 YL)PIPERIDINYL]THIOUREA HEMIFUMARATE; N (2 FLUOROBENZYL) N' [4 (1H IMIDAZOL 4 YL)PIPERIDINYL]THIOUREA HEMIFUMARATE; N (2 IODOBENZYL) N' [4 (1H IMIDAZOL 4 YL)PIPERIDINYL]THIOUREA HEMIFUMARATE; N (2 METHYLBENZYL) N' [4 (1H IMIDAZOL 4 YL)PIPERIDINYL]THIOUREA HEMIFUMARATE; N (2 TERT BUTYLBENZYL) N' [4 (1H IMIDAZOL 4 YL)PIPERIDINYL]THIOUREA; N (3 BROMOBENZYL) N' [4 (1H IMIDAZOL 4 YL)PIPERIDINYL]THIOUREA HEMIFUMARATE; N (3 CHLOROBENZYL) N' [4 (1H IMIDAZOL 4 YL)PIPERIDINYL]THIOUREA HEMIFUMARATE; N (3 FLUOROBENZYL) N' [4 (1H IMIDAZOL 4 YL)PIPERIDINYL]THIOUREA HEMIFUMARATE; N (3 IODOBENZYL) N' [4 (1H IMIDAZOL 4 YL)PIPERIDINYL]THIOUREA HEMIFUMARATE; N (4 BROMOBENZYL) N' [4 (1H IMIDAZOL 4 YL)PIPERIDINYL]THIOUREA HEMIFUMARATE; N (4 CHLOROBENZYL) N' [4 (1H IMIDAZOL 4 YL)PIPERIDINYL]THIOUREA HEMIFUMARATE; N (4 FLUOROBENZYL) N' [4 (1H IMIDAZOL 4 YL)PIPERIDINYL]THIOUREA HEMIFUMARATE; N (4 IODOBENZYL) N' [4 (1H IMIDAZOL 4 YL)PIPERIDINYL]THIOUREA HEMIFUMARATE; N BENZYL N' [4 (1H IMIDAZOL 4 YL)PIPERIDINYL]THIOUREA HEMIFUMARATE; THIOPERAMIDE; UNCLASSIFIED DRUG;

ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DRUG DESIGN; DRUG RECEPTOR BINDING; DRUG STRUCTURE; DRUG SYNTHESIS; GUINEA PIG; MOLECULAR MODEL; NONHUMAN; QUANTITATIVE STRUCTURE ACTIVITY RELATION; RECEPTOR AFFINITY;

BENZYL COMPOUNDS; BINDING SITES; HISTAMINE ANTAGONISTS; JEJUNUM; MODELS, MOLECULAR; MUSCLE CONTRACTION; MUSCLE, SMOOTH; PIPERIDINES; RADIOPHARMACEUTICALS; RECEPTORS, HISTAMINE H3; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0034030530     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm981106w     Document Type: Article

References (28)

1. Schwartz, J.-C.; Arrang, J.-M.; Garbarg, M.; Pollard, H.; Ruat, M. Histaminergic Transmission in the Mammalian Brain. Physiol. Rev. 1991, 71, 1-51.
2. Leurs, R.; Smit, M. J.; Timmerman, H. Molecular pharmacological aspects of histamine receptors. Pharmacol. Ther. 1995, 66, 413-463.
3. 3) of histamine receptor. Nature 1983, 302, 832-837.
4. 3 Receptors. Naunyn-Schmiedeberg's Arch. Pharmacol. 1989, 340, 633-638.
5. 3 Receptors in the Inhibitory Effect of Histamine on Serotonin Release in the Rat Brain Cortex. Naunyn-Schmiedeberg's Arch. Pharmacol. 1990, 342, 513-519.
6. Haas, H. L.; Sergueeva, O. A.; Vorobjev, V. S.; Sharonova, I. N. Subcortical modulation of synaptic plasticity in the hippocampus. Behav. Brain Res. 1995, 66, 41-44.
7. 3 receptors. J. Neural Transm.-Gen. Sect. 1993, 93, 1-10.
8. 3 agonists and antagonists. Trends Pharmacol. Sci. 1998, 19, 177-184.
9. Leurs, R.; Vollinga, R. C.; Timmerman, H. In Progress in Drug Research; Jucker, E., Ed.; Birkhauser Verlag: Basel, 1995; pp 107-165.
10. Vollinga, R. C. New ligands for the histamine H3 receptor. Ph.D. thesis, Vrije Universiteit, Amsterdam, The Netherlands, 1995.
11. 3 receptor antagonists. Eur. J. Pharm. Sci. 1997, 21, 507-520.
12. 3-receptor agonists. Quant. Struct.-Act. Relat. 1995, 14, 121-125.
13. 3 receptor explaining agonist versus antagonist activity simultaneously. Bioorg. Med. Chem., submitted.
14. Leurs, R.; Tulp, M. T.; Menge, W. M.; Adolfs, M. J.; Zuiderveld, O. P.; Timmerman, H. Evaluation of the receptor selectivity of the H3 receptor antagonists iodophenpropit and thioperamide: an interaction with the 5-HT3 receptor revealed. Br. J. Pharmacol. 1995, 116, 2315-2321.
15. 125I]-iodophenpropit binding. Brain Res. 1996, 743, 178-183.
16. 3 receptor antagonists: synthesis and evaluation of formamidine and S-methylisothiourea derivatives. Chem. Pharm. Bull. 1997, 45, 305-311.
17. Carpenter, A. J.; Chadwick, J. High Yielding Synthesis of 4(5)-Substituted Imidazoles via Organolithium Intermediates. The Utility of Sulphonamide N-Protecting and Silicon-Containing Blocking Groups. Tetrahedron 1986, 42, 2351-2358.
18. Chadwick, D. J.; Ngochindo, R. I. 2,5-Dilithation of N-Protected Imidazoles. Synthesis of 2,5-Disubstituted Derivatives of 1-Methoxymethyl-, 1-Triphenylmethyl-, and 1(N,N-Dimethylsulphonamido)-imidazole. J. Chem. Soc., Perkin Trans. I 1984, 481-486.
19. Ram, S.; Spicer, L. D. Debenzylation of N-benzylamino derivatives by catalytic transfer hydrogenation with ammoniumformate. Synth. Commun. 1987, 17, 415-418.
20. Staab, H. A.; Walther, G. Reaktionen von N,N′-Thiocarbonyldi-Imidazol. Justus Liebig's Ann. Chem. 1962, 657, 98-103.
21. Kim, S.; Yi, K. Y. Di-2-pyridyl thionocarbonate. A new reagent for the preparation of isothiocynates and carbodiimides. Tetrahedron Lett. 1985, 26, 1661-1664.
22. Yoon, N. M.; Brown, H. C. Selective reductions. XII. Explorations in some representative applications of aluminium hydride for selective reductions. J. Am. Chem. Soc. 1968, 90, 2827-2938.
23. Klouwen, M. H.; Boelens, H. Alkyl-substituted benzaldehydes. Red. Trav. Chim. Pays-Ban 1960, 79, 1022-1031.
24. Friedman, L.; Schechter, H. Dimethylformamide as a useful solvent in preparing nitriles from aryl halides and cuprous cyanide; Improved isolation techniques. J. Org. Chem. 1961, 26, 2522-2524.
25. 3 Ligands. Methods Fund. Clin. Pharmacol. 1992, 14, 747-751.
26. 3 receptor. Eur. J. Med. Chem. 1992, 27, 511-517.
27. 3 receptor antagonists: the effect of chain length variation of the alkyl spacer and modifications of the N-thiourea substituent. J. Med. Chem. 1995, 38, 2244-2250.
28. 3 receptor. J. Med. Chem. 1996, 39, 1220-1226.