A series of amino acid prodrugs of racemic and chiral 7-(3-amino-1-pyrrolidinyl)-6-fluoro-1,8-naphthyridine-3-carboxylic acids, 1-cyclopropyl-6,8-difluoro-3-quinolinecarboxylic acids, 1-cyclopropyl-6-fluoro-3-quinolinecarboxylic acids, and 5-amino-1-cyclopropyl-6,8-difluoro-3-quinolinecarboxylic acids have been prepared and evaluated for comparative antibacterial activity. Compounds were prepared by acylation of the 3-amino group of the pyrrolidine with common amino acids using standard peptide chemistry. This series has been compared with the parent compounds for antibacterial activity in vitro and in vivo as well as for comparative solubility. The amino acid analogues were less active in vitro, but had equal or increased efficacy in vivo. Indeed, it was proven that these compounds, which were stable to acid and base under the reaction conditions for their preparation, were rapidly cleaved in serum to give the parent quinolones. The amino acid derivatives showed a 3-70 times improved solubility when compared to the parent compounds. The most active compound of the series was [S-(R*,R*)]-7-[3-[(2-amino-1-oxopropyl)-amino]-1-pyrrolidinyl]-1- cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid (PD 131112).

中文翻译：

---

喹诺酮类抗菌剂。外消旋和手性7-（3-氨基-1-吡咯烷基）喹诺酮系列氨基酸前药的合成与构效关系。具有体内假单胞菌活性的高可溶性喹诺酮前药。

外消旋和手性7-（3-氨基-1-吡咯烷基）-6-氟-1,8-萘啶-3-羧酸，1-环丙基-6,8-二氟-3-喹啉羧酸的一系列氨基酸前药已经制备了丙烯酸，1-环丙基-6-氟-3-喹啉羧酸和5-氨基-1-环丙基-6,8-二氟-3-喹啉羧酸，并比较了其抗菌活性。使用标准肽化学方法，通过将吡咯烷的3-氨基与普通氨基酸酰化来制备化合物。已将该系列与母体化合物的体外和体内抗菌活性以及相对的溶解度进行了比较。氨基酸类似物在体外的活性较低，但在体内具有相同或更高的功效。实际上，已证明这些化合物，在制备的反应条件下对酸和碱稳定的二甲基吡啶在血清中迅速裂解，得到母体喹诺酮。与母体化合物相比，氨基酸衍生物的溶解度提高了3-70倍。该系列中活性最高的化合物是[S-（R *，R *）]-7- [3-[（2-氨基-1-氧丙基）-氨基] -1-吡咯烷基] -1-环丙基-6-氟-1,4-二氢-4-氧代-1,8-萘啶-3-羧酸（PD 131112）。