QUINOLINE COMPOUNDS, PREPARATION METHODS THEREOF, AND USES THEREOF AS URATE TRANSPORTER INHIBITOR DRUG

• US 20180362466A1
• Filed: 12/06/2016
• Published: 12/20/2018
• 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
• Granted Patent: US 10,450,274 B2
• Time in Patent Office: 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 (A) or optical isomers or solvates or pharmaceutically acceptable salts or pro-drugs thereof,

2. The compound according to claim 1, or optical isomers or solvates or pharmaceutically acceptable salts or pro-drugs thereof, where the compound has a structure of formula (I),

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 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 or C₃˜

C₆ cycloalkyl.

Preferably, R₁ is selected from the group of F, Br, Cl, pyridyl, pyrimidinyl, pyrrolyl, imidazolyl, phenyl, trifluoromethyl or cyclopropyl, wherein said phenyl is optionally further substituted by one or more substituents selected from the group of methoxy, ethoxy, fluorine, chlorine, bromine or trifluoromethyl.

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 selected from hydrogen, halogen or C₁-C₆ alkyl, respectively;

Preferably, R₂ is selected from hydrogen and R₃ is selected from methyl;

Or R₂ is selected from hydrogen and R₃ is selected from ethyl;

Or, R₂ is selected from hydrogen and R₃ is selected from isopropyl;

Or, R₂ and R₃ are both selected from methyl;

Or, R₂ and R₃ are both selected from ethyl;

Or, R₂ and R₃ are both selected from n-propyl.

5. The compound according to claim 4, or optical isomers or solvates or chemically pharmaceutically salts or pro-drugs thereof, where 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 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 or C₃-C₆ cycloalkyl;

Preferably, R₁ is selected from the group of F, Br, Cl, trifluoromethyl, pyridyl, pyrimidinyl, pyrrolyl, imidazolyl, phenyl or cyclopropyl, wherein said phenyl is optionally further substituted by one or more substituents selected from methoxy, ethoxy, fluorine, chlorine, bromine or trifluoromethyl;

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.

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 of

8. The method for preparation of compounds according to claim 1, that is characterized by including the procedure carried out by the following route,

9. The use of compounds according to claim 1 or optical isomers or solvates or pharmaceutically acceptable salts or pro-drugs thereof in the preparation of URAT1 inhibitory drugs.

10. The use according to claim 9, that is the drugs are those for the prevention and/or treatment of gout, recurrent gout attack, gouty arthritis, hyperuricemia, hypertension, cardiovascular diseases, coronary artery disease, Lesch-Nyhan syndrome, Kearns-Sayre Syndrome, nephropathy, kidney stone, renal failure, joint inflammation, arthritis, urolithiasis, lead poisoning, hyperparathyroidism, psoriasis, sarcoidosis or hypoxanthine-guanine phosphoribosyl transferase deficiency disease, and the drugs for prevention and/or treatment of gout or hyperuricemia are preferable.