Discovery of YFJ-36: Design, Synthesis, and Antibacterial Activities of Catechol-Conjugated β-Lactams against Gram-Negative Bacteria.

Cefiderocol is the first approved catechol-conjugated cephalosporin against multidrug-resistant Gram-negative bacteria, while its application was limited by poor chemical stability associated with the pyrrolidinium linker, moderate potency against and , intricate procedures for salt preparation, and potential hypersensitivity. To address these issues, a series of novel catechol-conjugated derivatives were designed, synthesized, and evaluated. Extensive structure-activity relationships and structure-metabolism relationships (SMR) were conducted, leading to the discovery of a promising compound (Code no.

Discovery of Thieno[2,3-]indazole Derivatives as Novel Oral Selective Estrogen Receptor Degraders with Highly Improved Antitumor Effect and Favorable Druggability.

Endocrine therapies in the treatment of early and metastatic estrogen receptor α positive (ERα+) breast cancer (BC) are greatly limited by and acquired resistance. Selective estrogen receptor degraders (SERDs) like fulvestrant provide new strategies for endocrine therapy combinations due to unique mechanisms. Herein, we disclose our structure-based optimization of LSZ102 by replacing 6-hydroxybenzothiophene with 6-thieno[2,3-]indazole.