(S)-spiro[(1,3-diazacyclopent-1-ene)-5,2'-(7'-methyl-1',2',3',4'- tetrahydronaphthalene)]: resolution, stereospecific synthesis, and preliminary pharmacological characterization as a partial alpha-adrenergic agonist.
Recently, we reported on the design, synthesis, and structure-activity relationships of a series of spiroimidazolines endowed with alpha-adrenergic agonist activities. Among the compounds described, (R,S)-spiro(1,3-diazacyclopent-1-ene)-[5,2'](7'-methyl-1'2',3', 4',-tetrahydronaphthalene) fumarate (5RS) was chosen for further development as a venotonic agent. The resolution of this compound, as well as the pharmacological characterization of the enantiomers, stereospecific synthesis of eutomer (5S, S 18149), and determination of absolute configuration by single-crystal X-ray diffraction analysis, are described.
Cordi
A A
AA
Institut de Recherches Servier, Suresnes, France.
Lacoste
J M
JM
Le Borgne
F
F
Herve
Y
Y
Vaysse-Ludot
L
L
Descombes
J J
JJ
Courchay
C
C
Laubie
M
M
Verbeuren
T J
TJ
D000316:Adrenergic alpha-Agonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D018360:Crystallography, X-Ray; D005263:Femoral Artery / Q000187:drug effects; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D012501:Saphenous Vein / Q000187:drug effects / Q000473:pathology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; C108184:S 18149; D013764:Tetrahydronaphthalenes; D010656:Phenylephrine; D015016:Yohimbine; D011224:Prazosin