Kanazawa K, Nouda H, Sunagawa M
Sumitomo Pharmaceuticals Research Center, Osaka, Japan.
J Antibiot (Tokyo). 1997 Feb;50(2):162-8. doi: 10.7164/antibiotics.50.162.
The anti-H. influenzae activity of meropenem (1a) was much higher than those of imipenem (4). panipenem (2b) and biapenem (7). To clarify the major structural features responsible for the anti-H. influenzae activity of carbapenem compounds, the structure-activity relationship to the anti-H. influenzae activity was investigated. The anti-H. influenzae activities of meropenem (1a) and 1 beta-methyl-panipenem (2a) were much higher than those of desmethyl-meropenem (1b) and panipenem (2b). respectively. Two carbapenems (5, 6) and imipenem (4), that have a strong basic C-2 side chain, showed lower anti-H. influenzae activity than meropenem (1a) having a weakly basic C-2 side chain and N-acetyl thienamycin (3) having a neutral C-2 side chain, respectively. As a result, we found that the introduction of the 1 beta-methyl group or the reduction of the basicity (cationic character) of the C-2 side chain increased the antimicrobial activity and bactericidal activity of carbapenems against H. influenzae due to their increased affinity for PBP-4 and PBP-5.
美罗培南（1a）对流感嗜血杆菌的活性远高于亚胺培南（4）、帕尼培南（2b）和比阿培南（7）。为阐明碳青霉烯类化合物抗流感嗜血杆菌活性的主要结构特征，研究了其结构与抗流感嗜血杆菌活性的关系。美罗培南（1a）和1β-甲基帕尼培南（2a）对流感嗜血杆菌的活性分别远高于去甲基美罗培南（1b）和帕尼培南（2b）。两种具有强碱性C-2侧链的碳青霉烯类化合物（5、6）和亚胺培南（4），其对流感嗜血杆菌的活性分别低于具有弱碱性C-2侧链的美罗培南（1a）和具有中性C-2侧链的N-乙酰硫霉素（3）。结果发现，引入1β-甲基基团或降低C-2侧链的碱性（阳离子特性）可提高碳青霉烯类化合物对流感嗜血杆菌的抗菌活性和杀菌活性，这是因为它们对PBP-4和PBP-5的亲和力增加。
