Continuous flow modular synthetic platform for accelerated drug discovery.

The efficient construction of structurally diverse and drug-like compound libraries remains a major bottleneck in modern drug discovery. To address this, we developed a fully automated modular flow synthesis platform that integrates continuous flow chemistry and automation technologies. This system enables rapid, high-throughput synthesis of complex molecules without intermediate purification. For the quinolone synthesis presented here, the platform achieved a 60-fold acceleration over conventional batch methods. To demonstrate the platform's versatility, we constructed a 409-member quinolone-based library through systematic structural diversification. Screening identified highly active candidates, including (S)-C-9-21 and C-1-13, which exhibited potent activity against multidrug-resistant bacterial strains, excellent safety profiles, and negligible cytotoxicity. In a murine thigh infection model, a 10 mg/kg dose of (S)-C-9-21 reduced bacterial load by 100-fold, matching the efficacy of vancomycin at 40 mg/kg. Beyond the discovery of promising antibiotic candidates, this work establishes a scalable, automated, and machine learning-ready platform that bridges the critical gap between synthetic chemistry and biological screening. Our approach provides a versatile blueprint for next-generation drug discovery, enabling rapid exploration of chemical space and accelerating the development of novel therapeutic agents.