Processes for preparing a diazabicyclooctane compound
Inventors
Abe, Takao • Furuuchi, Takeshi • Sakamaki, Yoshiaki • Inamura, Seiichi • Morinaka, Akihiro
Assignees
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Publication Number
US-10556905-B2
Publication Date
2020-02-11
Expiration Date
Abstract
A process for preparing a diazabicyclooctane compound represented by the following formula (I): wherein A represents RcO—; B represents NH or NC1-6 alkyl; C represents a benzyl group; Rc represents a C1-6 alkyl group; A is substituted with one substituent Fn1, wherein Fn1 represents an azetidine group; the process including: (a) silylating the compound represented by the following formula (IV-c): wherein in the formula (IV-c), OBn represents benzyloxy, and (b) carrying out an intramolecular urea formation reaction.
Core Innovation
The invention relates to diazabicyclooctane derivatives and related compounds defined by chemical formulae, including formula (I), (II), (IIa), (IIb), (III), and related intermediates. The description provides variable definitions for substituents such as TFA, OMe, Boc, Teoc, OBn, and Cbz, and includes salts, hydrates, solvates, and protected intermediates.
The disclosed subject matter focuses on sulfooxy-diazabicyclooctane compounds having a diazabicyclo[3.2.1]octane core with sulfooxy or sulfonate oxy substituents and carboxamide functionality. The examples and embodiments describe structural variation on aminooxy, aminoalkoxy, and other substituent patterns, together with protected and deprotected forms including benzyloxy and hydroxy precursors.
The patent further discloses optically active benzyloxy/TFA-protected diazabicyclooctane carboxylic acid intermediates and downstream sulfonic-acid derivatives, including ester/amides and conversion products obtained after benzyloxy hydrogenolysis to alcohols/acids. It also describes protected intermediate compounds for chemical synthesis, defined by chemical formulas containing protecting groups and structural relationships among protected intermediates, together with sodium sulfooxy-containing 1,6-diazabicyclo[3.2.1]octane-7-one-2-carboxamide derivatives and N-substituent oxygen functionalities.
Claims Coverage
The consolidated claim coverage includes one independent claim in the provided material, and dependent claims that narrow the scope by fixing specific named protecting-group definitions within selected chemical formulas. The inventive scope is centered on compounds defined by selected chemical formulas with explicit meanings for TFA, OMe, Boc, Teoc, OBn, and Cbz.
Compound defined by selected chemical formulas with named group substitutions
A compound of a formula selected from a group of chemical formulas, wherein TFA represents a trifluoroacetyl group, OMe represents a methoxy group, Boc represents a tert-butoxycarbonyl group, Teoc represents a 2-trimethylsilylethoxycarbonyl group, OBn represents a benzyloxy group, and Cbz represents a benzyloxycarbonyl group.
Formula variants with OBn, TFA, Boc, Teoc, and Cbz
Dependent claims specify particular formula instances including combinations such as OBn with TFA, OBn with Boc, OBn with Teoc, OBn with Boc and Cbz, and OBn with Cbz.
Overall, the claims cover selected chemical formulas defined by named protecting-group acronyms, with dependent claims narrowing the scope to specific formula variants distinguished by the presence and combination of OBn, TFA, Boc, Teoc, and Cbz.
Stated Advantages
Strong β-lactamase inhibition in class A/C/D, especially class C, ESBL, and KPC-2.
Potential antimicrobial synergy and recovery of β-lactam activity against resistant bacteria.
Improved, industrially feasible synthetic route versus prior art.
The document states therapeutic use of the invention’s compound in combination with β-lactam antibiotics to treat infections caused by class A/C β-lactamase producers and ESBL/KPC2 carbapenemase producers.
Documented Applications
Medicaments comprising the compounds of formula (I)/(II)/(III) and salts, hydrates and solvates.
Combination with β-lactam antibiotics for treating infections by β-lactamase/ESBL/KPC2-producing strains, including class A/class C β-lactamase producing strains.
Combination treatment embodiments for bacterial infection treatment using β-lactam antibiotics with the β-lactamase inhibitor.
Use in relation to bacterial resistance contexts involving β-lactamase-mediated resistance, specifically against ESBL and KPC-2.
Therapeutic use in combination with β-lactam antibiotics for infections caused by class A/C β-lactamase producers and ESBL/KPC2 carbapenemase producers, including Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, Morganella morganii, Pseudomonas aeruginosa, and Acinetobacter baumannii.
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