Synthesis of conformationally constrained analogues of BRL32872. Determination of stereochemistry and related pharmacological properties.

Bioorganic and Medicinal Chemistry Letters

Volumn 7, Issue 15, 1997, Pages 1989-1994

  Souchet, Michel ^a   Forest, Marie Claire ^a   Gerhard, Ute ^b   Smith, Richard J ^b   Cheval, Brigitte ^a   Rouanet, Sabine ^a   Faivre, Jean François ^a   Bril, Antoine ^a  

^a SmithKline Beecham Laboratoires P   (France)

^b GLAXOSMITHKLINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

2 AZABICYCLO[2.2.2]OCTANE DERIVATIVE; ANTIARRHYTHMIC AGENT; N (3,4 DIMETHOXYPHENYL) N [3 [N [2 (3,4 DIMETHOXYPHENYL)ETHYL] N METHYLAMINO]PROPYL] 4 NITROBENZAMIDE; UNCLASSIFIED DRUG;

ACTION POTENTIAL; ANIMAL TISSUE; ANTIARRHYTHMIC ACTIVITY; ARTICLE; CALCIUM CURRENT; CONTROLLED STUDY; DOSE RESPONSE; DRUG STRUCTURE; DRUG SYNTHESIS; GUINEA PIG; HEART; IN VITRO STUDY; MOLECULAR DYNAMICS; NONHUMAN; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PATCH CLAMP; REACTION ANALYSIS; STEREOCHEMISTRY;

ANIMALIA; CAVIA PORCELLUS; SUS SCROFA;

EID: 0030743297     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(97)00349-1     Document Type: Article

References (13)

1. Bril, A.; Faivre J.-F.; Forest M. C.; Cheval B.; Gout B.; Linée P.; Ruffolo R. R. Jr; Poyser R. H. J. Pharm. and Exp. Ther. 1995, 273, 1264-1272.
2. Gout, B.; Nichols A. J.; Feuerstein G. Z.; Bril A. J. Cardiovasc. Pharmacol. 1995, 26(6), 636-644.
3. a) Bakunov S. A.; Denisov A. Y.; Tkachev A. V. Tetrahedron 1995, 51, 8565-8572.
4. b) Asaoka M.; Ohkura N.; Yokota M.; Sonoda S.; Takei H. Heterocycles, 1994, 38, 2455-2462.
5. c) Szantay C.; Bolcskei H.; Gacs-Baitz E. Tetrahedron 1990, 46, 1711-1732.
6. d) Mehmandoust M.; Marazano C.; Singh R.; Gillet B.; Césario M.; Fourrey J.-L.; Das B. C. Tetrahedron Lett. 1988, 29, 4423-4426.
7. e) Trost B. M.; Romero A. G. J. Org. Chem. 1986, 51, 2332-2342.
8. f) Law, S.-J.; Lewis D. H.; Borne R. F. J. Heterocyclic Chem. 1978, 15, 273-280.
9. 2O (621.1): C 61.88, H 6.33, N 6.77, Cl 5.71; Found: C 61.89, H 6.33, N 6.81, Cl 5.54.
10. Identification of stereochemistry in a simpler series has been reported: Blaney F. E.; Hadley M. S.; King F. D.; Watts E. A. Eur. Patent 115 933, 1984.
11. 4-MeOH).
12. The result from the nOe difference study was confirmed by the coupling pattern of the protons H6 and H6'. The coupling pattern of the resonance of H6 δ 1.52 ppm results from a large geminal coupling and a small vicinal coupling whereas the resonance of H6' δ 2.67 ppm exhibits two large coupling constants.
13. -1 compare to the closest conformation without hydrogen bond. Calculations were performed using MM2 force-field from within MacroModel 5.0 software (Columbia University New York, NY 10027).