# US 8,785,403 B2 · Glucopyranoside compound

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 8,785,403 B2
- Document ID: US8785403B2
- Status: Granted
- Kind: B2
- Application number: 13/494,602
- Filed: 2012-06-12
- Published: 2012-10-11
- Granted: 2014-07-22
- Earliest claimed: 2003-08-01
- Assignees: Mitsubishi Tanabe Pharma Corporation
- Applicants: Sumihiro Nomura; Eiji Kawanishi; Kiichiro Ueta
- Inventors: Sumihiro Nomura; Eiji Kawanishi; Kiichiro Ueta
- Web page: https://patentgrep.com/patent/US8785403B2

## CPC

- C07H 19/056: Triazole or tetrazole radicals
- A61K 31/7042: Compounds having saccharide radicals and heterocyclic rings
- A61K 31/7056: containing five-membered rings with nitrogen as a ring hetero atom
- A61K 38/24: Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g. HCG; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
- A61K 38/28: Insulins
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- C07H 7/04: Carbocyclic radicals
- C07H 7/06: Heterocyclic radicals
- C07H 19/04: Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H 19/044: Pyrrole radicals
- C07H 19/048: Pyridine radicals
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

A compound of the formula: wherein Ring A and Ring B are: (1) Ring A is an optionally substituted unsaturated monocyclic heterocyclic ring, and Ring B is an optionally substituted unsaturated monocyclic heterocyclic ring, an optionally substituted unsaturated fused heterobicyclic ring, or an optionally substituted benzene ring, (2) Ring A is an optionally substituted benzene ring, and Ring B is an optionally substituted unsaturated monocyclic heterocyclic ring or an optionally substituted unsaturated fused heterobicyclic ring, or (3) Ring A is an optionally substituted unsaturated fused heterobicyclic ring, and Ring B are independently an optionally substituted unsaturated monocyclic heterocyclic ring, an optionally substituted unsaturated fused heterobicyclic ring, or an optionally substituted benzene ring; X is a carbon atom or a nitrogen atom; Y is —(CH2)n— (n is 1 or 2); or a pharmaceutically acceptable salt thereof, or a prodrug thereof.

## Claims

### Claim 1

A pharmaceutical composition comprising
(i) a compound of Formula (I):
wherein
Ring A is
wherein R1a, R2a, R3a, R1b, R2b, and R3b are each independently a hydrogen atom, a halogen atom, a hydroxy group, an alkoxy group, an alkyl group, a haloalkyl group, a haloalkoxy group, a hydroxyalkyl group, an alkoxyalkyl group, an alkoxyalkoxy group, an alkenyl group, an alkynyl group, a cycloalkyl group, a cycloalkylidenemethyl group, a cycloalkenyl group, a cycloalkyloxy group, a phenyl group, a phenylalkoxy group, a cyano group, a nitro group, an amino group, a mono- or di-alkylamino group, an alkanoylamino group, a carboxyl group, an alkoxycarbonyl group, a carbamoyl group, a mono- or di-alkylcarbamoyl group, an alkanoyl group, an alkylsulfonylamino group, a phenylsulfonylamino group, an alkylsulfinyl group, an alkylsulfonyl group, or a phenylsulfonyl group, and
Ring B is
wherein R4a is a phenyl group substituted by a halogen atom, a cyano group, an alkyl group, a haloalkyl group, an alkoxy group, a haloalkoxy group, an alkylenedioxy group, an alkyleneoxy group, a mono- or di-alkylamino group; or a heterocyclyl group substituted by a halogen atom, a cyano group, an alkyl group, a haloalkyl group, an alkoxy group, or a haloalkoxy group, where the heterocyclyl group is a thienyl group, a pyridyl group, a pyrimidinyl group, a pyrazinyl group, pyrazolyl group, a thiazolyl group, a quinolyl group, or a tetrazolyl group; R5a is a hydrogen atom;
X is a carbon atom; and
Y is —(CH2)n— (wherein n is 1 or 2);
or a pharmaceutically acceptable salt thereof;
(ii) an antidiabetic agent selected from the group consisting of insulin, an insulin secretagogue, an insulin sensitizer, a biguanide compound, a sulfonylurea compound, an α-glucosidase inhibitor, a PPARγ agonist, a PPARα/γ dual agonist, a dipeptidyl peptidase IV inhibitor, a mitiglinide compound, a nateglinide compound, a glucagon-like peptide-1, a PTP1B inhibitor, a glycogen phosphorylase inhibitor, a RXR modulator, and a glucose 6-phosphatase inhibitor; and
(iii) a pharmaceutically acceptable carrier.

### Claim 2 (depends on 1)

The pharmaceutical composition according to claim 1, wherein R1a, R2a, R3a, R1b, R2b, and R3b are each independently a hydrogen atom, a halogen atom, a lower alkyl group, a halo-lower alkyl group, a lower alkoxy group, or a phenyl group;
R4a is a phenyl group substituted by a halogen atom, a cyano group, a lower alkyl group, a halo-lower alkyl group, a lower alkoxy group, a halo-lower alkoxy group, a methylenedioxy group, an ethyleneoxy group, a mono- or di-lower alkylamino group; or a heterocyclyl group substituted by a halogen atom, a cyano group, a lower alkyl group, or a lower alkoxy group.

### Claim 3 (depends on 2)

The pharmaceutical composition according to claim 2, wherein Ring A is
wherein R1a is a halogen atom, a lower alkyl group, or a lower alkoxy group, and R2a and R3a are hydrogen atoms;
R4a is a phenyl group substituted by a substituent selected from the group consisting of a halogen atom, a cyano group, a lower alkyl group, a halo-lower alkyl group, a lower alkoxy group, a halo-lower alkoxy group, and a mono- or di-lower alkylamino group; or a heterocyclyl group substituted by a halogen atom, a cyano group, a lower alkyl group, or a lower alkoxy group, and Y is —CH2—.

### Claim 4 (depends on 1)

The pharmaceutical composition of claim 1, wherein R4a is a phenyl group substituted by a halogen atom, a cyano group, a lower alkyl group, a halo-lower alkyl group, a lower alkoxy group, or a halo-lower alkoxy group; or a heterocyclyl group substituted by a halogen atom, a cyano group, a lower alkyl group, or a lower alkoxy group.

### Claim 5 (depends on 1)

The pharmaceutical composition according to claim 1, wherein the compound is represented by the following formula:
wherein RA is a halogen atom, or a lower alkyl group; and
Ring C is a phenyl group substituted by 1-3 substituents selected from the group consisting of a halogen atom, a cyano group, a lower alkyl group, a halo-lower alkyl group, a lower alkoxy group, a halo-lower alkoxy group, a methylenedioxy group, an ethyleneoxy group, and a mono- or di-lower alkylamino group; or a heterocyclyl group substituted by 1-3 substituents selected from the group consisting of a halogen atom, a cyano group, a lower alkyl group, a halo-lower alkyl group, a lower alkoxy group, and a halo-lower alkoxy group; where the heterocyclyl group is a thienyl group, a pyridyl group, a pyrimidinyl group, a pyrazinyl group, pyrazolyl group, a thiazolyl group, a quinolyl group, or a tetrazolyl group;
or a pharmaceutically acceptable salt thereof.

### Claim 6 (depends on 5)

The pharmaceutical composition according to claim 5, wherein Ring C is a phenyl group substituted by 1-3 substituents selected from the group consisting of a halogen atom, a cyano group, a lower alkyl group, a halo-lower alkyl group, a lower alkoxy group, a halo-lower alkoxy group, and a mono- or di-lower alkylamino group; or a heterocyclyl group substituted by a substituent selected from the group consisting of a halogen atom, a cyano group, a lower alkyl group, a halo-lower alkyl group, a lower alkoxy group, and a halo-lower alkoxy group.

### Claim 7 (depends on 5)

The pharmaceutical composition according to claim 5, wherein Ring C is a phenyl group substituted by a halogen atom, a cyano group, a lower alkyl group, a halo-lower alkyl group, a lower alkoxy group, or a halo-lower alkoxy group; or a heterocyclyl group substituted by a halogen atom, a cyano group, a lower alkyl group, or a lower alkoxy group.

### Claim 8 (depends on 5)

The pharmaceutical composition according to claim 5, wherein Ring C is a phenyl group substituted by a halogen atom or a cyano group, or a pyridyl group substituted by a halogen atom.

### Claim 9 (depends on 1)

The pharmaceutical composition according to claim 1, wherein the compound is selected from the group consisting of:
1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene;
1-(β-D-glucopyranosyl)-4-chloro-3-[5-(3-cyanophenyl)-2-thienylmethyl]benzene;
1-(β-D-glucopyranosyl)-4-chloro-3-[5-(4-cyanophenyl)-2-thienylmethyl]benzene;
1-(β-D-glucopyranosyl)-4-methyl-3-[5-(6-fluoro-2-pyridyl)-2-thienylmethyl]benzene;
1-(β-D-glucopyranosyl)-4-chloro-3-[5-(6-fluoro-2-pyridyl)-2-thienylmethyl]benzene;
1-(β-D-glucopyranosyl)-4-methyl-3-[5-(3-difluoromethyl-phenyl)-2-thienylmethyl]benzene;
1-(β-D-glucopyranosyl)-4-methyl-3-[5-(3-cyanophenyl)-2-thienylmethyl]benzene;
1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-cyanophenyl)-2-thienylmethyl]benzene; and
1-(β-D-glucopyranosyl)-4-chloro-3-[5-(6-fluoro-3-pyridyl)-2-thienylmethyl]benzene;
or a pharmaceutically acceptable salt thereof.

### Claim 10 (depends on 1)

The pharmaceutical composition according to claim 1, wherein the compound is 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(3-cyano-phenyl)-2-thienylmethyl]benzene, or a pharmaceutically acceptable salt thereof.

### Claim 11 (depends on 1)

The pharmaceutical composition according to claim 1, wherein the compound is 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-cyano-phenyl)-2-thienylmethyl]benzene, or a pharmaceutically acceptable salt thereof.

### Claim 12 (depends on 1)

The pharmaceutical composition according to claim 1, wherein the compound is 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluoro-phenyl)-2-thienylmethyl]benzene, or a pharmaceutically acceptable salt thereof.

### Claim 13 (depends on 1)

The pharmaceutical composition according to claim 1, wherein the compound is 1-(β-D-glucopyranosyl)-4-chloro-3-[5-(3-cyano-phenyl)-2-thienylmethyl]benzene, or a pharmaceutically acceptable salt thereof.

### Claim 14 (depends on 1)

The pharmaceutical composition according to claim 1, wherein the compound is 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(6-fluoro-2-pyridyl)-2-thienylmethyl]benzene, or a pharmaceutically acceptable salt thereof.

### Claim 15 (depends on 1)

The pharmaceutical composition according to claim 1, wherein the compound is 1-(β-D-glucopyranosyl)-4-chloro-3-[5-(6-fluoro-2-pyridyl)-2-thienylmethyl]benzene, or a pharmaceutically acceptable salt thereof.

### Claim 16 (depends on 1)

The pharmaceutical composition according to claim 1, wherein the compound is 1-(β-D-glucopyranosyl)-4-chloro-3-[5-(6-fluoro-3-pyridyl)-2-thienylmethyl]benzene, or a pharmaceutically acceptable salt thereof.

### Claim 17 (depends on 1)

The pharmaceutical composition according to claim 1, wherein said antidiabetic agent is a biguanide compound.

### Claim 18 (depends on 1)

The pharmaceutical composition according to claim 1, wherein said antidiabetic agent is a dipeptidyl peptidase IV inhibitor.

### Claim 19 (depends on 1)

The pharmaceutical composition according to claim 1, wherein said antidiabetic agent is insulin.

### Claim 20 (depends on 1)

The pharmaceutical composition pharmaceutical composition according to claim 1, wherein said antidiabetic agent is an insulin secretagogue.

### Claim 21 (depends on 1)

The pharmaceutical composition according to claim 1, wherein said antidiabetic agent is a sulfonylurea compound.

### Claim 22 (depends on 1)

The pharmaceutical composition according the claim 1, wherein said antidiabetic agent is an α-glucosidase inhibitor.

### Claim 23 (depends on 1)

The pharmaceutical composition according to claim 1, wherein said antiabetic agent is a PPARγ agonist.

### Claim 24 (depends on 1)

The pharmaceutical composition according to claim 1, wherein said antidiabetic agent is a PPARα/γ dual agonist.

### Claim 25

A pharmaceutical composition comprising
(i) a compound having the following structure or a pharmaceutically acceptable salt thereof:
(ii) an antidiabetic agent selected from the group consisting of insulin, an insulin secretagogue, an insulin sensitizer, a biguanide compound, a sulfonylurea compound, an α-glucosidase inhibitor, a PPARγ agonist, a PPARα/γ dual agonist, a dipeptidyl peptidase IV inhibitor, a mitiglinide compound, a nateglinide compound, a glucagon-like peptide-1, a PTP1B inhibitor, a glycogen phosphorylase inhibitor, an RXR modulator, and a glucose 6-phosphatase inhibitor; and
(iii) a pharmaceutically acceptable carrier.

### Claim 26 (depends on 25)

The pharmaceutical composition of claim 25, wherein the antidiabetic agent is a biguanide compound.