Synthesis of new 3,4-disubstituted pyrrolidines as thromboxane A2/prostaglandin H2 (TP) receptor antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 6, Issue 4, 1996, Pages 349-352

  Dubuffet, Thierry ^a   Muller, Olivier ^a   Simonet, Serge S ^a   Descombes, Jean Jacques ^a   Laubie, Michel ^a   Verbeuren, Tony J ^a   Lavielle, Gilbert ^a  

^a INSTITUT DE RECHERCHES SERVIER   (France)

Author keywords

[No Author keywords available]

Indexed keywords

6 [2 (2 CHLOROPHENYL) 4 (2 HYDROXYPHENYL) 1,3 DIOXAN 5 YL] 4 HEXENOIC ACID; DRUG RECEPTOR; PYRROLIDINE DERIVATIVE; THROMBOXANE A2 RECEPTOR; THROMBOXANE A2 RECEPTOR BLOCKING AGENT;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; GUINEA PIG; HUMAN; HUMAN CELL; INTRAVENOUS DRUG ADMINISTRATION; NONHUMAN; NORMAL HUMAN; SMOOTH MUSCLE CONTRACTION; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION; THROMBOCYTE AGGREGATION; TRACHEA;

EID: 0029940045     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/0960-894X(96)00021-2     Document Type: Article

References (15)

1. Presented in part at the 23rd American Chemical National Medicinal Chemistry Symposium, Buffalo N.Y., Poster 48, June 14-18, 1992.
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9. The Z/E ratio for the two isomers formed during the Wittig reaction varied from 80/20 (R = benzyl) to 95/5 (R=n-hexCO). The Z isomer was isolated after HPLC.
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11. Use of KCN for the preparation of 11 led to a partial epimerisation at the benzylic carbon atom.
12. 1H NMR (DMSO-d6)δ 9.55 (S,1H), 8.8 (d,1H), 8.6 (d,1H), 8.5 (d,1H), 8.45 (d,1H), 7.9 (t,1H), 7.05 (t,1H), 6.75 (2d,2H), 6.5 (t,1H), 5.2 (m,J = 11, 1Hz, 1H), 5.1 (m,1H), 3.7 (m,2H), 3.6 (m,1H), 3.5-3.1 (dd,2H), 2.55 (m,1H), 2.1 (t,2H), 1.85 (m,2H), 1.6-1.45 (m,2H).
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