US 2010/0137388 A1 · Therapeutic Pro-Antibiotic Agents and Methods of Use Thereof

Abstract

The present invention provides for therapies characterized in part by co-administration or combination of antibiotic agents with medicinal compositions comprising as the pro-antibiotic active ingredient either a compound represented by a formula [I] or a pharmaceutically acceptable composite thereof; [wherein X represents oxygen, sulfur, NH, or N-alkyl; R1 and R2 represent hydrogen, tetrazole, or alkyltetrazole, respectively (with the restriction that if R1 is not hydrogen, R2 must be, and vice versa); R3 represents e.g., benzyl, phenyl optionally substituted, biphenyl, napthyl, N-phenylcarboxamido, etc., R4 represents e.g. carboxylic acid, or its alkyl esters, or a bioisoteric equivalent thereof, etc.; R5 represents e.g. hydrogen, carboxylic acid, etc.] in particular, medicine which is useful as therapeutic and/or protective drugs for infectious and/or inflammatory diseases. Other relevant compounds are also provided.

Claims17

Dependent claims

A compounds or pharmaceutically acceptable salt thereof comprising the structure of Formula I,

wherein
X is O, S, NH, or N-alkyl;
R1 and R2 are each, independently, hydrogen, tetrazole, alkylcarboxytetrazole, or alkyltetrazole (with the proviso that if R1 is not hydrogen, R2 must be, and vice versa);
R3 is a halogen, alkyl halogen, 1,2-diphenylethyl, m-acrylylphenyl, substituted or unsubstituted N-phenylcarboxamido, substituted or unsubstituted alkyl, substituted or unsubstituted aryl or arylalkyl or substituted or unsubstituted heteroaryl or heteroarylalkyl;
R4 is carboxylic acid or its alkyl esters, or a bioisosteric equivalent thereof, where R4 may be connected cis or trans to the double bond and R5 will necessarily be in the cis/trans position opposite to that of R4;
and
R5 is hydrogen, or carboxylic acid or its alkyl esters, or a bioisosteric equivalent thereof.

4 more elements

A compound selected from the group consisting of (Z)-methyl 3-(5-benzyl-4-(1H-tetrazol-5-yl)thiophen-2-yl)acrylate, (E)-methyl 3-(5-benzyl-4-(1H-tetrazol-5-yl)thiophen-2-yl)acrylate, (Z)-3-(5-benzyl-4-(1H-tetrazol-5-yl)thiophen-2-yl)acrylic acid, (E)-3-(5-benzyl-4-(1H-tetrazol-5-yl)thiophen-2-yl)acrylic acid, (E)-methyl 3-(5-benzyl-4-(1-methyl-1H-tetrazol-5-yl)thiophen-2-yl)acrylate, (E)-methyl 3-(5-benzyl-4-(2-methyl-2H-tetrazol-5-yl)thiophen-2-yl)acrylate, (E)-3-(5-benzyl-4-(2-methyl-2H-tetrazol-5-yl)thiophen-2-yl)acrylic acid, (E)-3-(5-benzyl-4-(1-methyl-1H-tetrazol-5-yl)thiophen-2-yl)acrylic acid, (E)-3-(5-(4-fluorophenyl)-4-(1H-tetrazol-5-yl)thiophen-2-yl)acrylic acid, (E)-3-(5-(4-biphenylyl)-4-(1H-tetrazol-5-yl)thiophen-2-yl)acrylic acid, (E)-methyl 3-(5-(naphthalen-1-yl)-4-(1H-tetrazol-5-yl)thiophen-2-yl)acrylate, (E)-3-(5-(naphthalen-1-yl)-4-(1H-tetrazol-5-yl)thiophen-2-yl)acrylic acid, (E)-methyl 3-(5-(4-fluorophenyl)-3-(1H-tetrazol-5-yl)thiophen-2-yl)acrylate, (E)-3-(5-(4-fluorophenyl)-3-(1H-tetrazol-5-yl)thiophen-2-yl)acrylic acid, (E)-methyl 3-(5-(4-fluorophenyl)-3-(2-methyl-2H-tetrazol-5-yl)thiophen-2-yl)acrylate, (E)-3-(5-(4-fluorophenyl)-3-(2-methyl-2H-tetrazol-5-yl)thiophen-2-yl)acrylic acid, (E)-3-(5-(4-fluorophenyl)-3-(1-methyl-1H-tetrazol-5-yl)thiophen-2-yl)acrylic acid, (E)-methyl 3-(4-(2-methyl-2H-tetrazol-5-yl)-5-(naphthalen-1-yl)thiophen-2-yl)acrylate, (E)-methyl 3-(5-(4-biphenyl)-3-(1H-tetrazol-5-yl)thiophen-2-yl)acrylate, (E)-3-(5-(biphenyl-4-yl)-3-(1H-tetrazol-5-yl)thiophen-2-yl)acrylic acid, (E)-methyl 3-(5-benzyl-3-(1H-tetrazol-5-yl)thiophen-2-yl)acrylate, 5-((5-benzyl-3-(1H-tetrazol-5-yl)thiophen-2-yl)methylene)thiazolidine-2,4-dione, 2-((5-benzyl-4-(1H-tetrazol-5-yl)thiophen-2-yl)methylene)malonic acid, (E)-3-(5-benzyl-4-(2-(2-carboxyethyl)-2H-tetrazol-5-yl)thiophen-2-yl)acrylic acid, (E)-3-(3-((5-((E)-2-carboxyvinyl)-3-(1H-tetrazol-5-yl)thiophen-2-yl)methyl)phenyl)acrylic acid.

Dependencies are inferred from the claim text.

Therapeutic Pro-Antibiotic Agents and Methods of Use Thereof

Life of this patent

Therapeutic Pro-Antibiotic Agents and Methods of Use Thereof

Life of this patent

Abstract

Claims17