Cephalosporin derivatives and methods of use

Patent metadata

Field	Value
Publication number	US-10059722-B2
Application number	US-201314439373-A
Country	US
Kind code	B2
Filing date	Nov 4, 2013
Priority date	Nov 2, 2012
Publication date	Aug 28, 2018
Grant date	Aug 28, 2018

Abstract

This invention provides cephalosporin derivatives for killing or inhibiting the spread of microorganisms such as non-replicating Mycobacterium tuberculosis and in the treatment of infectious disease.

First claim

What is claimed is:

1. A compound having the structure of Formula I or V, or a pharmaceutically acceptable salt thereof:

wherein
X is N;
R 3 is H, CH 3 or —CR 7 ;
R 4 is C 1 -C 10 alkyl, —COO − , —COOH, —CR 7 , —C(═O)OR 7 , —C(═O)OCR 7 , —C(═O)C(—CH 3 )OR 7 , —CH 2 OR 7 , —C(═O)CH 2 CH 2 R 7 or —NHR 6 ;
R 5 is C 1 -C 10 alkyl, —CR 7 , —C(═O)COR 7 , —C(═O)C(—CH 3 )OR 7 , —CH 2 OR 7 , or —NHR 6 ;
R 6 is C 1 -C 10 alkyl, C 3 -C 7 cycloalkyl, aryl, heteroaryl, or —CR 7 ; and
R 7 is C 2 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, C 3 -C 7 cycloalkyl, unsubstituted aryl, heteroaryl or aryl substituted with an alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, alkylaryl, heteroaralkyl, heteroarylalkenyl, heteroarylalkynyl, alkylheteroaryl, hydroxy, hydroxyalkyl, alkoxy, aryloxy, aralkoxy, alkoxyalkoxy, acyl, halo, cyano, carboxy, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, alkylthio, arylthio, heteroarylthio, aralkylthio, heteroaralkylthio, cycloalkyl, or heterocyclyl group.

2. A pharmaceutical composition for killing or inhibiting the spread of a microorganism comprising one or more compounds having the structure of Formula I or V, or a pharmaceutically acceptable salt thereof, in admixture with a pharmaceutically acceptable carrier,

wherein
X is N;
R 3 is H, CH 3 or —CR 7 ;
R 4 is C 1 -C 10 alkyl, —COO − , —COOH, —CR 7 , —C(═O)OR 7 , —C(═O)OCR 7 , —C(═O)C(—CH 3 )OR 7 , —CH 2 OR 7 , —C(═O)CH 2 CH 2 R 7 or —NHR 6 ;
R 5 is C 1 -C 10 alkyl, —CR 7 , —C(═O)OR 7 , —C(═O)COR 7 , —C(═O)OCR 7 , —C(═O)C(—CH 3 )OR 7 , —CH 2 OR 7 , —C(═O)CH 2 CH 2 R 7 or —NHR 6 ;
R 6 is C 1 -C 10 alkyl, C 3 -C 7 cycloalkyl, aryl, heteroaryl, or —CR 7 ; and
R 7 is C 2 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, C 3 -C 7 cycloalkyl, aryl, or heteroaryl.

3. The pharmaceutical composition of claim 2 , further comprising one or more antitubercular agents.

4. The compound of claim 1 , wherein:
X is N;
R 3 is H, CH 3 or —CR 7 ;
R 4 is —COO − , —COOH, —C(═O)OR 7 , —C(═O)OCR 7 , —C(═O)C(—CH 3 )OR 7 , or —C(═O)CH 2 CH 2 R 7 ;
R 5 is —C(═O)COR 7 , or —C(═O)C(—CH 3 )OR 7 ; and
R 7 is C 2 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, C 3 -C 7 cycloalkyl, unsubstituted aryl, or heteroaryl or aryl substituted with an alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, alkylaryl, heteroaralkyl, heteroarylalkenyl, heteroarylalkynyl, alkylheteroaryl, hydroxy, hydroxyalkyl, alkoxy, aryloxy, aralkoxy, alkoxyalkoxy, acyl, halo, cyano, carboxy, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, alkylthio, arylthio, heteroarylthio, aralkylthio, heteroaralkylthio, cycloalkyl, or heterocyclyl group.

5. The pharmaceutical composition of claim 2 , wherein:
X is N;
R 3 is H, CH 3 or —CR 7 ;
R 4 is —COO − , —COOH, —C(═O)OR 7 , —C(═O)OCR 7 , —C(═O)C(—CH 3 )OR 7 or —C(═O)CH 2 CH 2 R 7 ;
R 5 is —C(═O)OR 7 , —C(═O)COR 7 , —C(═O)OCR 7 , —C(═O)C(—CH 3 )OR 7 , or —C(═O)CH 2 CH 2 R 7 ; and
R 7 is C 2 -C 10 alkyl, C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, C 3 -C 7 cycloalkyl, aryl, or heteroaryl.

6. A pharmaceutical composition for killing or inhibiting the spread of a microorganism comprising a compound having the structure:

or a pharmaceutically acceptable salt thereof, in admixture with a pharmaceutically acceptable carrier.

Assignees

• Univ Kansas
• Univ Cornell

Inventors

• Aube Jeffrey
• Nathan Carl
• Smith Robert
• Gold Ben S
• Hanson Paul
• Liu Chunjing
• Mitscher Lester Allen
• Pingle Maneesh
• Schoenen Frank John

Classifications

• C07D513/04

  Ortho-condensed systems · CPC title

• C07D501/16 Primary

  with a double bond between positions 2 and 3 · CPC title

• C07D499/44

  Compounds with an amino radical acylated by carboxylic acids, attached in position 6 · CPC title

• C07D417/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D277/06

  with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms · CPC title