2-aza-substituted 1-carbadethiapen-2-em-3 carboxylic acids

• Main Authors: CHABALA; JOHN C, RATCLIFFE; RONALD W, CHRISTENSEN; BURTON G
• Format: Patent
• Language: English
• Published: 01.11.1988
• Edition: 4
• Subjects: CHEMISTRY; CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION ORPROCESSING OF GOODS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS; TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINSTCLIMATE CHANGE

Disclosed are 2-aza-substituted 1-carbadethiapen-2-em-3-carboxylic acids I, where the generic 2-aza group includes azido, acylamino, amino, alkylamino, dialkylamino, trizolyl, triazolinyl, aziridinyl, and their pharmaceutically acceptable salt, ester, anhydride and amide derivatives which are useful as antibiotics. Also disclosed are processes for the preparation of I from the known, appropriately substituted bicyclic keto ester II via the 2-azido central intermediate III: I II III wherein R16 is H or CH3, preferably beta-methyl; R6, and R7 are independently hydrogen, linear, branched or cyclic C1-C5alkyl, which can be substituted with fluoro, hydroxy, protected hydroxy, sulfoxy, amino, protected amino, wherein R6 and R7 taken together can also be C2-C4 alkylidene, similarly substituted; with the proviso that both R6 and R7 are not unsubstituted alkyl, R1 and R2 are, inter alia, hydrogen, alkyl, acyl, and can be joined to form a ring comprising 3 to 7 atoms; Ra is hydrogen, a salt cation, a removable protecting group, or a pharmaceutically acceptable ester moiety. Also disclosed are processes for the preparation of such compounds; pharmaceutical compositions comprising such compounds; and methods of treatment comprising administering such compounds and compositions when an antibiotic effect is indicated.