US 6,476,015 B1 · N-thiolated β-lactam antibiotics

Abstract

Substituted monocyclic β-lactam compounds that are N-1-thiolated monolactams, and which exhibit wide-ranging antibacterial activities, having a single 4-membered azetidinone ring in which: the N-1 nitrogen atom of the azetidinone ring is bonded to sulfur but is not sulfonated, of the formula: wherein R1-5 are independently hydrogen, alkyl, heteroalkyl, aryl, heteroaryl, alkenyl, or alkynyl; X is H, C, or O; and n=0-3. Chemical synthesis of these compounds by a [2+2]-imine-acid chloride cycloaddition, and methods for subsequent derivatization, are also disclosed. The compounds and compositions disclosed herein are useful as antibacterial and antibiotic agents.

Claims20

Dependent claims

A monocyclic β-lactam compound of the formula:

or a salt or hydrate thereof, wherein:
—C(R1)3 is methyl, ethyl, —CH2Ph or benzyl;
—X(R2)n is methoxy, hydrogen, or X(R2)n and R4 forms a spirocycle
R3 is acetyl, aryl, heteroaryl, aryl(C1-C6)alkyl, heteroaryl(C1-C6)alkyl, aryl(C2-C6)alkenyl, heteroaryl(C2-C6)alkenyl, aryl(C2-C6)alkynyl or heteroaryl(C2-C6)alkynyl;
wherein any aryl or heteroaryl is optionally substituted with halo, nitro, cyano, hydroxy, trifluoromethyl, trifluoromethoxy, (C1-C15)alkyl, (C2-C15)alkenyl, (C2-C15)alkynyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(C1-C15)alkyl, (C3-C8)cycloalkyl-C2-C15)alkenyl, (C3-C8)cycloalkyl(C2-C15)alkynyl, (C1-C15)alkoxy, (C1-C15)alkanoyl, (C1-C15)alkanoyloxy, C(O)O(C1-C6)alkyl, C(═O)N((C1-C6)alkyl)2, or N((C1-C6)alkyl)2;
R4 is hydrogen, or X(R2)n and R4 forms a spirocycle;
R5 is hydrogen;
and
excluding the compounds 1-thiomethyl-3-methoxy-4-phenylethynyl-2-oxoazetidine, and 1-thiomethyl-3-methoxy-4-(O-acetyl)phenylethynyl-2oxoazetidine.

6 more elements

Dependencies are inferred from the claim text.

N-thiolated β-lactam antibiotics

Life of this patent

N-thiolated β-lactam antibiotics

Life of this patent

Abstract

Claims20