Sulfur(VI) fluoride compounds and methods for the preparation thereof

Patent metadata

Field	Value
Publication number	US-10765645-B2
Application number	US-201816158608-A
Country	US
Kind code	B2
Filing date	Oct 12, 2018
Priority date	Jun 6, 2014
Publication date	Sep 8, 2020
Grant date	Sep 8, 2020

Abstract

This application describes a compound represented by Formula (I):

Y Z X 1 —S(O)(X 2 )F) m ] n   (I)

wherein: Y is a biologically active organic core group comprising one or more of an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group, to which Z is covalently bonded; n is 1, 2, 3, 4 or 5; m is 1 or 2; Z is O, NR, or N; X 1 is a covalent bond or —CH 2 CH 2 —, X 2 is O or NR; and R comprises H or a substituted or unsubstituted group selected from an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group. Methods of preparing the compounds, methods of using the compounds, and pharmaceutical compositions comprising the compounds are described as well.

First claim

We claim:

1. A method of preparing a compound of Formula (I):
Y Z X 1 —S(O)(X 2 )F) m ] n   (I)

wherein at least one Z of the compound is N or NR;
the method comprising reacting a precursor antibiotic bearing an NH 2 or NHR substituent with CH 2 ═CH—SO 2 F by a Michael addition to replace the hydrogens of the NH 2 or the hydrogen of the NHR with —CH 2 CH 2 —SO 2 F;

wherein:
Y is an antibiotic core group comprising one or more unsubstituted or substituted moiety selected from an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, a nonaromatic heterocyclic group, to which each Z independently is covalently bonded;
n is 1, 2, 3, 4 or 5;
each Z independently is NR, or N;
when Z is NR, m is 1, X 1 is a covalent bond or CH 2 CH 2 , and the Z is covalently bonded to a nonaromatic hydrocarbyl, a nonaromatic heterocyclic, an aryl, or heteroaryl moiety of Y;
when Z is N, either (a) m is 2, X 1 is CH 2 CH 2 and the Z is covalently bonded to a nonaromatic hydrocarbyl, a nonaromatic heterocyclic, an aryl, or a heteroaryl moiety of Y; or (b) m is 1, X 1 is a covalent bond or CH 2 CH 2 , and the Z is a nitrogen in an aromatic or non-aromatic heterocyclic ring portion of core group Y;
each X 2 independently is O or NR; and
each R independently comprises H or a substituted or unsubstituted group selected from an aryl group, a heteroaryl aryl group, a nonaromatic hydrocarbyl group, and a nonaromatic heterocyclic group.

2. The method of claim 1 , wherein the antibiotic is selected from the group consisting of a cephalosporin, ciprofloxacin, sulfacetamide, amoxicillin, sulfanilamide, sulfamethoxazole, norfloxacin, gatifloxacin, gemifloxacin, trimethoprim, pyrimethamine, cefadroxil, isoniazid, streptomycin, moxifloxacin, and aminosalicylic acid.

3. The method of claim 1 , wherein the antibiotic is selected from the group consisting of a cephalosporin or ciprofloxacin.

4. The method of claim 1 , wherein the precursor bearing an NH 2 group is cefadroxil and the cefadroxil is reacted with at least two equivalents of CH 2 ═CH—SO 2 F to produce a product of formula:

Assignees

• Scripps Research Inst

Inventors

• Dong Jiajia
• Sharpless K Barry
• Kelly Jeffery W
• Baranczak Aleksandra
• Chen Wentao

Classifications

• A61K31/05 Primary

  Phenols {(cannabinoids A61K31/658)} · CPC title

• C07D501/18

  7-Aminocephalosporanic or substituted 7-aminocephalosporanic acids · CPC title

• A61K31/4353

  ortho- or peri-condensed with heterocyclic ring systems · CPC title

• A61K31/7048

  having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin {, digitoxin or digoxin} · CPC title

• A61P25/24

  Antidepressants · CPC title