Assandri A, Perazzi A, Bellasio E, Ciabatti R, Tarzia G, Ferrari P, Ripamonti A, Tuan G, Zerilli L F
Xenobiotica. 1985 Dec;15(12):1089-102. doi: 10.3109/00498258509049103.
The metabolic fate of a new anti-hypertensive, 1-pyrrolyl-pyridazinamine, was studied in male Beagle dogs given both p.o. and i.v. doses of the 14C-labelled drug (1 mg/kg). The compound given as a single i.v. injection disappeared from the central compartment with a half-life of about 0.9 h. Plasma levels of total 14C were represented mostly by metabolites. Eight urinary metabolites designated as metabolites I, II and XI-XVI were purified and their structures assigned by means of u.v., i.r., n.m.r. and mass spectrometry. Quantitatively the primary metabolic attack involved the morpholine moiety of the molecule which undergoes oxidative opening. A minor pathway afforded the cleavage of the pyrrole followed by chemical rearrangements to form six-membered sidnone-like products or a triazole derivative. The major (XIII) and three minor metabolites were studied for their antihypertensive activity in rats and were shown to be inactive.
对一种新型抗高血压药物1-吡咯基哒嗪胺的代谢命运进行了研究，研究对象是口服和静脉注射14C标记药物（1mg/kg）的雄性比格犬。单次静脉注射该化合物后，它从中央室消失，半衰期约为0.9小时。血浆中总14C水平主要由代谢产物代表。8种尿代谢产物被命名为代谢产物I、II和XI - XVI，通过紫外、红外、核磁共振和质谱对其进行了纯化并确定了结构。从数量上看，主要的代谢攻击涉及分子中的吗啉部分，该部分发生氧化开环。一条次要途径是吡咯的裂解，随后进行化学重排，形成六元环类似西多宁的产物或三唑衍生物。对主要代谢产物（XIII）和三种次要代谢产物在大鼠体内的抗高血压活性进行了研究，结果表明它们无活性。
