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1£¬Biginelli , P. Gazz. Chim. Ital . 1893 , 23 , 360.

2£¬Kappe , C. O. Tetrahedron 1993 , 49 , 6937.

3£¬Grover , G. J . ; Dzwonczyk , S. ; McMullen , D. M. ; Grover ,C. S. ; Sleph , P. G. ; Moreland , S. J . J . Cardiovasc. Pharmacol . 1995 , 26 , 289.

4£¬Atwal , K. S. ; Swanson , B. N. ; Unger , S. E. ; Floyd , D. M. ; Moreland , S. ; Hedberg , A. ; O¡äeilly , B. C. J . Med. Chem. 1991 , 34 , 806.

5£¬Rovnyak , G. C. ; Atwal , K. S. ; Hedberg , A. ; Kim2 ball , S. D. ; Moreland , S. ; Gougoutas , J . Z. ; O¡¯eil2ly , B. C. ; Schwartz , J . ; Malley , M. F. J . Med.Chem. 1992 , 35 , 3254.

6£¬Nagarathnam , D. ; Miao , S. W. ; Lagu , B. ; Chiu , G. ; Fang , J . ; MDhar , T. G. ; Zhang , J . ; Tyagarajan , S. ; Marzabadi , M. R. ; Zhang , F. Q. ; Wong , W. C. ; Sun , W. Y. ; Tian , D. ; Wetzel , J . M. ; Forray , C. ; Chang , R. S. L. ;Broten , T. P. ; Ransom , R. W. ;Schorn , T. W. ; Chen , T. B. ; O¡äMalley , S. ;Kling , P. ; Schneck , K. ; Benedesky , R. ; Harrell , C. M. ; Vyas , K. P. ;Gluchowski , C. J . Med. Chem. 1999 , 42 , 4764.

7£¬Barrow , J . C. ; Nantermet , P. G. ; Selnick , H. G. ; Glass , K. L. ; Rittle , K. E. ; Gilbert , K. F. ; Steele , T. G. ; Homnick , C. F. ; Freidinger , R. M. ; Ransom , R. W. ; Kling , P. ; Reiss , D. ; Broten , T. P. ; Schorn , T. W. ; Chang , R. S. L. ; O¡äMalley , S. S. ; Olah , T. V. ; Ellis , J . D. ; Barrish , A. ; Kassahun , K. ; Leppert , P. ; Nagarathnam , D. ; Forray , C. J . Med. Chem. 2000 , 43 , 2703.

8£¬Ma , Y. ; Qian , C. ; Wang , L. ; Yang , M. J . Org. Chem. 2000 , 65 , 3864.

9£¬Ranu , B. C. ; Hajra , A. ; Jana , U. J . Org. Chem. 2000 , 65 , 6270.

10£¬Wipf , P. ; Cunningham , A. Tetrahedron Lett . 1995 , 36 ,7819.

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6. Design and Synthesis of Novel 1a Adrenoceptor-Selective Antagonists. 1. Structure-Activity Relationship in Dihydropyrimidinones

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Aldehyde-urea derivatives of aceto-and oxaloacetic acids
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2.100 years of the Biginelli dihydropyrimidine synthesis     ¡¶TETRAHEDRON¡·  Kappe C O   1993 / 49 / P 6937
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3.Titre du document / Document title
Pharmacologic profile of the dihydropyrimidine calcium channel blockers SQ 32,547 and SQ 32,946
Auteur(s) / Author(s)
GROVER G. J. ; DZWONCZYK S. ; MCMULLEN D. M. ; NORMANDIN D. E. ; PARHAM C. S. ; SLEPH P. G. ; MORELAND S. ;
Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)
Bristol-Myers Squibb pharmaceutical res. inst., dep. pharmacology, Princeton NJ 08543, ETATS-UNIS

R¨¦sum¨¦ / Abstract
SQ 32,926 and SQ 32,547, two dihydropyrimidine calcium channel blockers, were characterized as potent inhibitors of depolarization-induced contractions of isolated smooth muscle preparations. In rat aorta, the IC50 values were 5.5 nM for SQ 32,547 and 8.1 nM for SQ 32,926, values which compare favorably with that of 2.9 nM for nifedipine. The dihydropyrimidines were also tested in a model of stable angina : pacing-induced ischemia in dogs. Both SQ 32,547 and SQ 32,926 reduced the ST-segment elevation observed in vehicle-treated animals. No significant changes in hemodynamic status were detected, suggesting that a reduction in cardiac work secondary to afterload reduction was probably not a major contributor to the protective effects. Neither was increased coronary blood flow important for the antiischemic outcome because no significant effects of the dihydropyrimidines were observed on ischemic regional blood flow. SQ 32,547 was also studied in globally ischemic, isolated rat hearts. In this model, SQ 32,547 was protective because it significantly reduced contracture formation and lactate dehydrogenase (LDH) release. Washing out the effect of SQ 32,547 in isolated hearts and smooth muscles was difficult, presumably due to its lipophilicity. In the smooth muscle preparations, the effects of both nifedipine and SQ 32,926 were much more easily washed out. As with other calcium channel blockers, increasing the antiischemic effects of SQ 32,547 was associated with a higher cost in terms of cardiac function. In summary, the two novel dihydropyrimidines, SQ 32,547 and SQ 32,926, showed antiischemic properties in animal models.
Revue / Journal Title
Journal of cardiovascular pharmacology   ISSN 0160-2446   CODEN JCPCDT  
Source / Source
1995, vol. 26, no2, pp. 289-294 (24 ref.)
Langue / Language
Anglais

Editeur / Publisher
Lippincott, Hagerstown, MD, ETATS-UNIS (1979) (Revue)

Mots-cl¨¦s anglais / English Keywords
Calcium antagonist ; Antiïschemic ; Angina pectoris ; Chemotherapy ; Treatment ; Smooth muscle ; Heart ; Rat ; Animal ; In vivo ; In vitro ; Rodentia ; Mammalia ; Vertebrata ; Cardiovascular disease ; Coronary heart disease ;
Mots-cl¨¦s français / French Keywords
Antagoniste calcium ; Antiisch¨¦mique ; Angine poitrine ; Chimioth¨¦rapie ; Traitement ; Muscle lisse ; Coeur ; Rat ; Animal ; In vivo ; In vitro ; SQ 32 547 ; SQ 32 946 ; Dihydropyrimidine d¨¦riv¨¦ ; Cardioprotecteur ; Rodentia ; Mammalia ; Vertebrata ; Appareil circulatoire pathologie ; Cardiopathie coronaire ;
Mots-cl¨¦s espagnols / Spanish Keywords
Antagonista calcio ; Antiisqu¨¦mico ; Angina pectoris ; Quimioterapia ; Tratamiento ; M¨²sculo liso ; Coraz¨®n ; Rata ; Animal ; In vivo ; In vitro ; Rodentia ; Mammalia ; Vertebrata ; Aparato circulatorio patolog¨ªa ; Cardiopat¨ªa coronaria ;
Localisation / Location
INIST-CNRS, Cote INIST : 18065, 35400005361515.0140
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