Barocelli E, Chiavarini M, Ballabeni V, Mingiardi M R, Morini G, Ronchini F, Impicciatore M
Istituto di Farmacologia e Farmacognosia, Facoltà di Farmacia, Università di Parma.
Boll Soc Ital Biol Sper. 1992 Jul;68(7):445-51.
This paper reports the pharmacological assessment of beta-blocking properties of new benzisothiazole and benzisoxazole derivatives, substituted in position 3-, 5- or 7- with the oxypropanolaminic side chain (I-VI), to of which contain the -OCH3 group in position 3- (III, V) in comparison with propranolol. The results, obtained on isoprenaline-induced chronotropic response of rat isolated atria and on isoprenaline-induced relaxation of guinea-pig tracheal strips precontracted by carbachol, suggest that the compounds (I, II, IV, VI), at variance with the methoxy-substituted (III, V), possess a beta 1-blocking activity 4-300 times lower than propranolol. pA2 values drop from 8.36 to 7.56 and 7.04 from the relative compounds substituted in position 7- (IV), 3- (I) and 5- (II), thus indicating that the position of the oxypropanolaminic chain in the benzisothiazole ring affects the ability of the molecules to interact with the beta 1-adrenoceptor. Furthermore, benzisothiazole rather than benzisoxazole ring seems to facilitate the drug-beta 1 adrenoceptor interaction, the compound (I) displaying a 10-fold higher affinity than compound (VI).
本文报道了新的苯并异噻唑和苯并异恶唑衍生物的β-阻断特性的药理学评估，这些衍生物在3-、5-或7-位被氧丙醇胺侧链取代（I-VI），其中3-位含有-OCH₃基团（III、V），并与普萘洛尔进行了比较。在大鼠离体心房对异丙肾上腺素诱导的变时反应以及对卡巴胆碱预收缩的豚鼠气管条对异丙肾上腺素诱导的舒张反应中获得的结果表明，与甲氧基取代的化合物（III、V）不同，化合物（I、II、IV、VI）具有比普萘洛尔低4-300倍的β₁-阻断活性。pA₂值从7-位取代的相关化合物（IV）、3-位取代的（I）和5-位取代的（II）的8.36降至7.56和7.04，这表明氧丙醇胺链在苯并异噻唑环中的位置影响分子与β₁-肾上腺素受体相互作用的能力。此外，苯并异噻唑环而非苯并异恶唑环似乎更有利于药物与β₁-肾上腺素受体的相互作用，化合物（I）的亲和力比化合物（VI）高10倍。
