941586-83-0

Upstream product

• 941585-43-9 7(S)-1′-N-(tert-butoxycarbonyl)-1′-demethyl-7-deoxy-7-{5-(2-nitrophenyl)-1,3,4-thiadiazol-2-ylthio}lincomycin 
• 941585-28-0 1′-N-(tert-butoxycarbonyl)-1′-demethyl-2,3,4-tris-O-(trimethylsilyl)lincomycin 
• 1089131-96-3 1′-N-(tert-butoxycarbonyl)-1′-demethyllincomycin 
• 314082-71-8 benzyl (2S,4R)-4-allyl-1N-tert-butoxycarbonylpyrrolidine-2-carboxylate 

Downstream Products

• 941587-04-8 7(S)-1′-demethyl-7-deoxy-7-{5-(2-nitrophenyl)-1,3,4-thiadiazol-2-yl}thio-1′-N-i-propyllincomycin 

Relevant academic research and scientific papers

Synthesis and structure-activity relationships of novel lincomycin derivatives. Part 4: Synthesis of novel lincomycin analogs modified at the 6- and 7-positions and their potent antibacterial activities

To modify lincomycin (LCM) at the C-6 and the C-7 positions, we firstly prepared various substituted proline intermediates (7, 11-15 and 17). These proline intermediates were coupled with methyl 1-thio-α-lincosamide and tetrakis-O-trimethylsilylation followed by selective deprotection of the TMS group at the 7-position gave a wide variety of key intermediates (23-27, 47 and 50). Then, we synthesized a variety of novel LCM analogs modified at the 7-position in application of the Mitsunobu reaction, an S N 2 reaction, and a Pd-catalyzed cross-coupling reaction. Compounds 34 and 35 (1′-NH derivatives) exhibited enhanced antibacterial activities against resistant pathogens with erm gene compared with the corresponding 1′-N-methyl derivatives (3 and 37). On the basis of reported SAR, we modified the 4′-position of LCM derivatives possessing a 5-(2-nitrophenyl)-1,3,4-thiadiazol-2-yl group at the C-7 position. Compound 56 showed significantly potent antibacterial activities against S. pneumoniae and S. pyogenes with erm gene, and its activities against S. pneumoniae with erm gene were improved compared with those of 34 and 57. Although we synthesized novel analogs by transformation of a C-7 substituent focusing on the 1′-demethyl framework to prepare very potent analogs 73 and 75, it was impossible to generate novel derivatives exhibiting stronger antibacterial activities against S. pneumoniae with erm gene compared with 56.

LINCOMYCIN DERIVATIVE AND ANTIBACTERIAL AGENT CONTAINING THE SAME AS ACTIVE INGREDIENT

This invention provides compounds of formula (I) or its pharmacologically acceptable salt or solvate, wherein A represents aryl or a monocyclic or bicyclic heterocyclic group, R1 represents a halide, nitro, substituted C1-6 alkyl, optionally substituted amino, C1-6 alkyloxycarbonyl, optionally substituted aryl, a heterocyclic group, or heterocyclic carbonyl, R2 represents a hydrogen atom or C1-6 alkyl, R3 represents C1-6 alkyl, all of R4, R5, and R6 represent a hydrogen atom, R7 represents C1-6 alkyl, m is 1 or 2, and n is 1. The compounds are novel lincomycin derivatives having a potent activity against resistant pneumococci. The compounds can be used as an antimicrobial agent and are useful for preventing or treating bacterial infectious diseases.