Quinoline compounds, preparation methods thereof, and uses thereof as urate transporter inhibitor drug

• US 10,450,274 B2
• Filed: 12/06/2016
• Issued: 10/22/2019
• Est. Priority Date: 12/07/2015
• Status: Active Grant

• Current Assignee: Hinova Pharmaceuticals Inc.
• Original Assignee: Hinova Pharmaceuticals Inc.
• Inventors: Fan, Lei, Du, Wu, Li, Xinghai, Chen, Yuanwei, Xu, Kexin, Chen, Ke, Zhang, Shaohua, Luo, Tongchuan
• Primary Examiner(s): Seaman, D Margaret M
• Application Number:
  US15/781,997
• Publication Number:
  US 20180362466A1
• Time in Patent Office: 1,050 Days
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61K 31/4709 Non-condensed quinolines and containing further heterocyclic rings
• CPC Class Codes: A61P 13/04 for urolithiasis
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/06 Antigout agents, e.g. antihyperuricemic or uricosuric agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 39/02 Antidotes
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/16 for decreasing, blocking or antagonising the activity of the thyroid hormones
• CPC Class Codes: A61P 5/18 of the parathyroid hormones
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07D 215/36 Sulfur atoms C07D215/24 takes precedence
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links

Abstract

Quinoline compounds and salts, hydrates or solvates serving as a selective uric acid reabsorption inhibitor, can be used in the treatment of hyperuricemia and gout by promoting uric acid to excrete from the body and reducing serum uric acid. Such compounds have the effect of reducing the uric acid in the animal body and human body.

Claims

1. A compound of formula (I) or optical isomers or solvates or pharmaceutically acceptable salts or pro-drugs thereof,

2. The compound according to claim 1, wherein,

R₁ is selected from the group consisting of halogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted cycloalkyl,

R₂ and R₃ are independently selected from the group consisting of halogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted cycloalkyl,

R₄ is hydrogen, C₁-C₆ alkyl, or C₃-C₆cycloalkyl.

3. The compound according to claim 1, or optical isomers or solvates or pharmaceutically acceptable salts or pro-drugs thereof, wherein, R₁ is selected from the group consisting of halogen, substituted or unsubstituted aryl, substituted or unsubstituted pyridyl, substituted or unsubstituted pyrimidinyl, substituted or unsubstituted pyrrolyl, substituted or unsubstituted imidazolyl, substituted or unsubstituted furyl, substituted or unsubstituted thienyl, substituted or unsubstituted oxazolyl, substituted or unsubstituted thiazolyl, substituted or unsubstituted oxdiazolyl, substituted or unsubstituted thiadiazolyl, and C₃-C₆ cycloalkyl.

4. The compound according to claim 1, or optical isomers or solvates or pharmaceutically acceptable salts or pro-drugs thereof, wherein, R₂ and R₃ are independently halogen or C₁-C₆ alkyl.

5. The compound according to claim 4, or optical isomers or solvates or chemically pharmaceutically salts or pro-drugs thereof, wherein the compound has the structure of formula (Id) or (Ie):

6. The compound according to claim 5, or optical isomers or solvates or pharmaceutically acceptable salts or pro-drugs thereof, wherein, R₁ is selected from the group consisting of halogen, trifluoromethyl, substituted or unsubstituted aryl, substituted or unsubstituted pyridyl, substituted or unsubstituted pyrimidinyl, substituted or unsubstituted pyrrolyl, substituted or unsubstituted imidazolyl, substituted or unsubstituted furyl, substituted or unsubstituted thienyl, substituted or unsubstituted oxazolyl, substituted or unsubstituted thiazolyl, substituted or unsubstituted oxdiazolyl, substituted or unsubstituted thiadiazolyl, and C₃-C₆ cycloalkyl.

7. The compound according to claim 1, or optical isomers or solvates or chemically acceptable salts or pro-drugs, that are selected from the group consisting of

8. The method for preparation of compounds according to claim 1, comprising:

9. A method of treating abnormal uric acid levels, comprising administering the compound according to claim 1 or the optical isomer or the solvate or the pharmaceutically acceptable salt or the pro-drugs thereof to a patient in need thereof.

10. A method of treating diseases characterized by abnormal uric acid levels, wherein the diseases are selected from gout, gout attack, gouty arthritis and hyperuricemia, comprising administering a compound according to claim 1 or the optical isomer or the solvate or the pharmaceutically acceptable salt or the prodrug thereof to a patient in need thereof.

11. The compound according to claim 2, wherein R₁ is selected from the group consisting of F, Br, Cl, pyridyl, pyrimidinyl, pyrrolyl, imidazolyl, phenyl, trifluoromethyl, and cyclopropyl, wherein said phenyl is optionally further substituted by one or more substituents selected from the group consisting of methoxy, ethoxy, fluorine, chlorine, bromine, and trifluoromethyl.

12. The compound according to claim 4, wherein

R₂ and R₃ are both methyl;

or, R₂ and R₃ are both ethyl;

or, R₂ and R₃ are both n-propyl.

13. The compound according to claim 6, wherein

R₁ is selected from the group consisting of F, Br, Cl, trifluoromethyl, pyridyl, pyrimidinyl, pyrrolyl, imidazolyl, phenyl, and cyclopropyl, wherein said phenyl is optionally further substituted by one or more substituents selected from the group consisting of methoxy, ethoxy, fluorine, chlorine, bromine, and trifluoromethyl, wherein the pharmaceutically acceptable salts thereof include the salts formed with bases, and sodium salt is preferable;

further includes the salts formed with the pharmaceutically acceptable acids.