9136. Temocapril
Nomenclature
CAS number: 111902-57-9
(2S,6R)-6-[[(1S)-1-(Ethoxycarbonyl)-3-phenylpropyl]amino]tetrahydro-5-oxo-2-(2-thienyl)-1,4-thiazepine-4(5H)-acetic acid; (+)-(2S,6R)-6-[[(1S)-1-carboxy-3-phenylpropyl]amino]tetrahydro-5-oxo-2-(2-thienyl)-1,4-thiazepine-4(5H)-acetic acid, 6-ethyl ester. C23H28N2O5S2; mol wt 476.61.
C 57.96%, H 5.92%, N 5.88%, O 16.78%, S 13.46%.
Description and references
Angiotensin-converting enzyme (ACE) inhibitor. Hydrolyzed in vivo to the active diacid metabolite. Prepn: H. Yanagisawa et al., EP 161801; eidem, US 4699905 (1985, 1987 both to Sankyo); idem et al., J. Med. Chem. 30, 1984 (1987). Pharmacology: K. Oizumi et al., Jpn. J. Pharmacol. 48, 349 (1988). GC/MS determn in human plasma and urine: H. Shioya et al., J. Chromatogr. 496, 129 (1989). Clinical evaluation: M. Arita et al., Clin. Exp. Pharmacol. Physiol. 21, 195 (1994); and pharmacokinetics: S. Tokunaga et al., Drug Invest. 7, 161 (1994). Review: H. Koike et al., Annu. Rep. Sankyo Res. Lab. 44, 1-81 (1992).
Properties
Cryst powder, mp 168°. [α]23 +40° (c = 1.1 in DMF).Derivative
Hydrochloride.Nomenclature
CAS number: 110221-44-8
CS-622; Acecol (Sankyo). Properties
Solid from ethanol/ethyl acetate, mp 187° (dec). [α]25D +47.7° (c = 1 in DMF). LD50 in mice, rats, dogs (mg/kg): >5000, >5000, >800 orally (Koike).Derivative
Diacid.Nomenclature
CAS number: 110221-53-9
Temocaprilat; RS-5139. C21H24N2O5S2; mol wt 448.56.
C 56.23%, H 5.39%, N 6.25%, O 17.83%, S 14.30%.
Properties
Solid from ethanol, mp 246° (dec). [α]25D +63.4° (c = 1 in DMF).Therapeutic Category
Antihypertensive.
Keywords
ACE-Inhibitor; Antihypertensive; N-Carboxyalkyl (peptide/lactam) Derivatives