Diarylamide compound and application thereof

Patent metadata

Field	Value
Publication number	US-12428389-B2
Application number	US-202017619174-A
Country	US
Kind code	B2
Filing date	Jun 19, 2020
Priority date	Jun 19, 2019
Publication date	Sep 30, 2025
Grant date	Sep 30, 2025

Abstract

A use of a diarylamide compound having the structure as shown in formula (I) or a pharmaceutically acceptable salt thereof in preparing a drug which acts as a urea transporter protein inhibitor, and a novel diarylamide compound. The diarylamide compound has urea transporter protein inhibitor effect, and can produce urea selective diuresis in the body without obvious toxicity.

First claim

What is claimed is:

1. A method for treating diseases related to a urea transporter inhibitor, comprising administering a therapeutically effective amount of a compound represented by formula (I-a) or a pharmaceutically acceptable salt thereof to a patient in need thereof,

wherein,
R 1 is selected from the group consisting of nitro, halogen, alkylcarbonyl, alkylcarbonylamino, alkylsulfonyl and pyrido groups;
R 2 is selected from the group consisting of halogen, hydroxy, amino, cyano, alkenyl, alkynyl, hydroxyalkyl, aminoalkyl, alkoxy, alkylcarbonyl, alkoxycarbonyl, pyrido, alkylcarbonylamino optionally substituted with R 5 , heterocyclic or cyclic group optionally substituted with R 5 , heteroarylcarbonylamino optionally substituted with R 5 , N-alkylamino, N,N-di (alkyl) amino, and aminocarbonyl substituted with R 3 and R 4 ;
wherein, R 3 and R 4 are each independently selected from the group consisting of H, hydroxyl, alkyl, heterocyclic or cyclic group optionally substituted with R 5 , heterocyclic or cyclic alkyl optionally substituted with R 5 , heteroaryl or aryl alkyl optionally substituted with R 5 , N-(alkyl) aminoalkyl, and N,N-di (alkyl) aminoalkyl;
and R 5 is selected from the group consisting of alkyl, nitro, alkylcarbonylamino, N-(alkyl) amino, N,N-di (alkyl) amino, N,N-di (alkyl) aminoalkylamino, and heterocyclic or cyclic group.

2. The method according to claim 1 , wherein the definitions of each group satisfy one or more of the followings:
R 1 is selected from the group consisting of nitro, halogen, C 1-6 alkyl, C 1-6 alkylcarbonyl, C 1-6 alkylcarbonylamino, C 1-6 alkylsulfonyl and pyrido groups;
R 2 is selected from the group consisting of halogen, hydroxyl, amino, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, hydroxy C 1-6 alkyl, amino C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, pyrido, C 1-6 alkylcarbonylamino optionally substituted with R 5 , 5- to 6-membered heterocyclic or cyclic group optionally substituted with R 5 , 5- to 6-membered heteroarylcarbonylamino optionally substituted with R 5 , N-(C 1-6 alkyl)amino, N,N-di(C 1-6 alkyl)amino, and aminocarbonyl substituted with R 3 and R 4 ;
wherein, R 3 and R 4 are each independently selected from the group consisting of H, hydroxyl, C 1-6 alkyl, 5- to 6-membered heterocyclic or cyclic group optionally substituted with R 5 , 5- to 6-membered heterocyclic or cyclic C 1-6 alkyl optionally substituted with R 5 , 5- to 6-membered heteroaryl or aryl C 1-6 alkyl optionally substituted with R 5 , N—(C 1-6 alkyl)amino C 1 -C 6 alkyl, and N,N-di(C 1-6 alkyl)amino C 1-6 alkyl; and R 5 is selected from the group consisting of C 1-6 alkyl, nitro, C 1-6 alkylcarbonylamino, N—(C 1-6 alkyl)amino, N,N-di(C 1-6 alkyl)amino, alkyl)amino C 1-6 alkylamino, and 5- to 6-membered heterocyclic or cyclic group.

3. A method for treating diseases related to a urea transporter inhibitor, comprising administering a therapeutically effective amount of a compound selected from the group consisting of the following compounds (2) to (79), or the pharmaceutically acceptable salts thereof:
(2)N-(4-acetylphenyl)-5-nitrofuran-2-carboxamide;
(3)N-(4-acetamidophenyl)-5-nitrofuran-2-carboxamide;
(4)N-(4-acetamidophenyl)furan-2-carboxamide;
(5)N-phenyl-5-nitrofuran-2-carboxamide;
(7)N-[4-(acetylamino)phenyl]-1H-pyrrole-2-carboxamide;
(8)N-(4-acetamidophenyl)oxazole-5-carboxamide;
(9)N-(4-acetamidophenyl)-5-nitrothiophene-2-carboxamide;
(10)N-(pyridin-2-yl)-5-nitrofuran-2-carboxamide;
(23)N-(4-acetamidophenyl)-5-bromofuran-2-carboxamide;
(24)N-(4-acetamidophenyl)-5-acetamidofuran-2-carboxamide;
(25)N-(4-acetamidophenyl)-5-methylsulfonylfuran-2-carboxamide;
(26)N-(2-acetamidophenyl)-5-nitrofuran-2-carboxamide;
(27)N-(3-acetamidophenyl)-5-nitrofuran-2-carboxamide;
(28)N-(3-methylphenyl)-5-nitrofuran-2-carboxamide;
(29)N-(2-methoxyphenyl)-5-nitrofuran-2-carboxamide;
(30)N-(3-methoxyphenyl)-5-nitrofuran-2-carboxamide;
(31)N-(4-methoxyphenyl)-5-nitrofuran-2-carboxamide;
(32)N-(3-hydroxyphenyl)-5-nitrofuran-2-carboxamide;
(33)N-(4-hydroxyphenyl)-5-nitrofuran-2-carboxamide;
(34)N-(3-aminophenyl)-5-nitrofuran-2-carboxamide;
(35)N-(2-fluorophenyl)-5-nitrofuran-2-carboxamide;
(36)N-(3-fluorophenyl)-5-nitrofuran-2-carboxamide;
(37)N-(4-fluorophenyl)-5-nitrofuran-2-carboxamide;
(38)N-(3-chlorophenyl)-5-nitrofuran-2-carboxamide;
(39)N-(4-chlorophenyl)-5-nitrofuran-2-carboxamide;
(40)N-(3-cyanophenyl)-5-nitrofuran-2-carboxamide;
(41)N-(4-cyanophenyl)-5-nitrofuran-2-carboxamide;
(42) ethyl 3-(5-nitrofuran-2-carboxamido)benzoate;
(43) ethyl 4-(5-nitrofuran-2-carboxamido)benzoate;
(44)N-(3-carbamoylphenyl)-5-nitrofuran-2-carboxamide;
(45)N-(4-carbamoylphenyl)-5-nitrofuran-2-carboxamide;
(46)N-(3-acetylphenyl)-5-nitrofuran-2-carboxamide;
(47)N-(4-dimethylaminophenyl)-5-nitrofuran-2-carboxamide;
(48)N-(4-morpholinylphenyl)-5-nitrofuran-2-carboxamide;
(49)N-(4-(4-ethylpiperazin-1-yl)phenyl)-5-nitrofuran-2-carboxamide;
(50)N-(4-(2-hydroxyethyl)phenyl)-5-nitrofuran-2-carboxamide;
(51)N-(4-aminomethylphenyl)-5-nitrofuran-2-carboxamide;
(52) N,N′-(1,4-phenylene)bis(5-nitrofuran-2-carboxamide);
(53)N-(3-(methylcarbamoyl)phenyl)-5-nitrofuran-2-carboxamide;
(54)N-(3-(dimethylcarbamoyl)phenyl)-5-nitrofuran-2-carboxamide;
(55)N-(3-(ethylcarbamoyl)phenyl)-5-nitrofuran-2-carboxamide;
(56)N-(3-(isopropylcarbamoyl)phenyl)-5-nitrofuran-2-carboxamide;
(57)N-(3-(isobutylcarbamoyl)phenyl)-5-nitrofuran-2-carboxamide;
(58)N-(3-(cyclohexylcarbamoyl)phenyl)-5-nitrofuran-2-carboxamide;
(59)N-(3-(benzylcarbamoyl)phenyl)-5-nitrofuran-2-carboxamide;
(60)N-(3-((2-dimethylaminoethyl)carbamoyl)phenyl)-5-nitrofuran-2-carboxamide;
(61)N-(3-((2-morpholinylethyl)carbamoyl)phenyl)-5-nitrofuran-2-carboxamide;
(62)N-(3-((3-morpholinylpropyl)carbamoyl)phenyl)-5-nitrofuran-2-carboxamide;
(63)N-(4-methyl-3-methylcarbamoylphenyl)-5-nitrofuran-2-carboxamide;
(64)N-(5-methyl-3-methylcarbamoylphenyl)-5-nitrofuran-2-carboxamide;
(65)N-(4-fluoro-3-methylcarbamoylphenyl)-5-nitrofuran-2-carboxamide;
(66)N-(5-fluoro-3-methylcarbomoylphenyl)-5-nitrofuran-2-carboxamide;
(67)N-(4-hydroxy-3-methylcarbamoylphenyl)-5-nitrofuran-2-carboxamide;
(68) N 1 ,N 3 -dimethyl-5-(5-nitrofuran-2-carboxamido)isophthalamide;
(69)N-(2-methyl-1,3-dihydro-1,3-dioxo-2H-isoindol-5-yl)-5-nitrofuran-2-carboxamide;
(70)N-(4-acetamidophenyl)-5-acetylfuran-2-carboxamide;
(71)N-(4-(2-dimethylamino)acetamidophenyl)-5-nitrofuran-2-carboxamide;
(72)N-(4-(2-morpholinyl)acetamidophenyl)-5-nitrofuran-2-carboxamide;
(73)N-(4-(3-dimethylamino)propionamidophenyl)-5-nitrofuran-2-carboxamide;
(74)N-(4-((2-dimethylamino)ethylamino)acetamidophenyl)-5-nitrofuran-2-carboxamide;
(75) ethyl 2-acetylamino-5-[[(5-nitro-2-furanyl)carbonyl]amino]benzoate;
(78) 5-Acetyl-N-[3-[(methyamino)carbonyl]phenyl]2-furancarboxamide;
and (79)N-3-(ethynylphenyl)-5-nitrofuran-2-carboxamide.

4. The method according to claim 1 , wherein the compound represented by formula (I) or the pharmaceutically acceptable salt thereof is one for treating diseases related to the urea transporter inhibitor; or, the drug is a diuretic or antihypertensive drug.

5. The method according to claim 4 , wherein the diseases related to the urea transporter inhibitor are edema diseases related to the urea transporter inhibitor.

6. The method according to claim 5 , wherein the edema diseases include: cardiogenic edema; nephrogenic edema; hepatogenic edema; dystrophic edema; edema due to connective tissue diseases; allergic edema; endocrine edema; idiopathic edema; venous obstructive edema; lymphatic obstructive

Assignees

• Sunshine Lake Pharma Co Ltd

Inventors

• Yang Baoxue
• Li Runtao
• Li Min
• Zhang Shun
• Zhao Yan
• Wang Shuyuan

Classifications

• C07D405/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D333/38

  Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title

• C07D307/68

  Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen · CPC title

• C07D263/34

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms · CPC title

• C07D207/34

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms · CPC title