Ohi N, Aoki B, Kuroki T, Matsumoto M, Kojima K, Nehashi T
J Antibiot (Tokyo). 1987 Jan;40(1):22-8. doi: 10.7164/antibiotics.40.22.
The resistance of 6-[(R)-2-[3-(3,4-dihydroxybenzoyl)-3-(3-hydroxypropyl)-1-ureido]-2- phenylacetamido]penicillanic acid (1a) to metabolism by catechol-O-methyl-transferase (COMT) was increased by introduction of the chlorine atom into the catechol moiety. Penicillins (1b-1d) having one or two chlorine atoms at the positions adjacent to the hydroxyl group were found to have greater stability to COMT. This resulted in greater efficiency in vivo in experimental Pseudomonas aeruginosa and Escherichia coli infections. In vitro activities were essentially unchanged.
通过在儿茶酚部分引入氯原子，6-[(R)-2-[3-(3,4-二羟基苯甲酰基)-3-(3-羟丙基)-1-脲基]-2-苯乙酰胺基]青霉烷酸（1a）对儿茶酚-O-甲基转移酶（COMT）代谢的抗性增强。发现在与羟基相邻位置具有一个或两个氯原子的青霉素（1b - 1d）对COMT具有更高的稳定性。这导致在实验性铜绿假单胞菌和大肠杆菌感染中体内效率更高。体外活性基本未变。
