US 2025/0025438 A1Published application

Derivative of aspartic acid and use thereof in treatment of metabolic diseases such as hepatic fibrosis and non-alcoholic hepatitis

AssigneeShenzhen Jingtai Technology Co., Ltd.

InventorsJie GAO, Huimin CHENG, Jun CHENG, Peiyu ZHANG

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Abstract

The present invention relates to compounds of Formula I and Formula II and the use thereof in the treatment of metabolic diseases such as liver fibrosis and non-alcoholic hepatitis. Specifically, provided are the compounds as shown, and pharmaceutically acceptable salts or esters, prodrug, stereoisomers, hydrates, solvates, crystalline forms and metabolite forms thereof, or any combination or mixture thereof in the preparation of a drug or reagent, the drug being used for at least one of the following: A-(L1)x-A′ (Formula I); A1-(L1); -A1′ (Formula II).

Claims14

Dependent claims

Use of a compound represented by the following Formula I, or pharmaceutically acceptable salt, ester, prodrug, stereoisomer, hydrate, solvate, isotopic compound, crystalline form, metabolite form thereof, or any combination or mixture thereof, in the manufacture of a medicament or agent, wherein the medicament is used for at least one of the following:

1) treating, improving, or preventing a liver disease (e.g., NAFLD, NASH, liver fibrosis);
2) alleviating a mammalian liver fibrosis, liver steatosis, or inflammation;
3) inhibiting the activation of stellate cells;
4) regulating the expression of NS3TP1;
A-(L1)x-A′ (Formula I)
wherein, A is
A′ is
A and A′ are the same or different;
wherein:
x is selected from the group consisting of 0, 1 and 2;
1) when x is 0, A′ is absent;
for A, wherein:
R1 and R2 are each independently selected from the group consisting of:
C1-C6 alkyl, —O—Ra1, and —NRa2Ra3;
R3 and R4 are each independently selected from the group consisting of:
hydrogen, deuterium, hydroxyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, —C(Rh)2—Rd1, —(CO)-(L)n-Rd2, —(CO)O-(L)n-Rd3, —(SO2)-(L)n-Rd4, and —P(O)(ORe)2, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, aryl (or C6-C12 aryl), and heterocyclyl;
Ra1, Ra2, and Ra3 are each independently selected from the group consisting of:
hydrogen, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, -(C1-C6 alkyl)n-(CO)—Rb1, -(C1-C6 alkyl)n-(CO)—O—Rb2, -(C1-C6 alkyl)n-O—(CO)—Rb3, -(C1-C6 alkyl)n-O—(CO)—O—Rb4, -(C1-C6 alkyl)n-(CO)—NRb5Rb6, -(C1-C6 alkyl)n-NRb7—(CO)—Rb8, and -(C1-C6 alkyl)n-NRb9—(CO)—O—Rb10, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, amino, hydroxyl, C1-C6 alkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, -(C1-C6 alkyl)-(C6-C10 aryl), and -(C1-C6 alkyl)-(3- to 15-membered heterocyclyl);
Rb1, Rb2, Rb3, Rb4, Rb5, Rb6, Rb7, Rb8, Rb9, Rb10 are each independently selected from the group consisting of:
hydrogen, deuterium, hydroxyl, amino, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, -(C1-C6 alkyl)n-(CO)—O—Rc1, -(C1-C6 alkyl)n-O—(CO)—Rc2, and -(C1-C6 alkyl)n-O—(CO)—O—Rc3, the alkyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, amino, hydroxyl, carboxyl, C1-C6 alkyl, and C6-C10 aryl;
Rc1, Rc2, and Rc3 are each independently selected from the group consisting of:
hydrogen, deuterium, hydroxyl, amino, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl;
L is each independently selected from the group consisting of:
absence, O, NRd5, C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl;
Re is each independently selected from the group consisting of hydrogen, deuterium, Na, K, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, C1-C6 alkyl, and halogenated C1-C6 alkyl;
Rh is each independently selected from the group consisting of:
C1-C6 alkyl, —NHC(O)Rg1, —OC(O)Rg2, —OP(O)(ONa)2, —NHC(O)ORd6, —OC(O)ORd7, and —OC(O)NHRd8;
Rd1, Rd2, Rd3, Rd4, Rd5, Rd6, Rd7, Rd8 are each independently selected from the group consisting of:
hydrogen, deuterium, amino, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more Rf groups;
Rf is each independently selected from the group consisting of halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C6-C10 aryl, halogenated C6-C10 aryl, C3-C7 cycloalkyl, 3- to 15-membered heterocyclyl, —NRg3Rg4, —ORg5, —NHC(O)Rg6, and —OC(O)Rg7;
Rg1, Rg2, Rg3, Rg4, Rg5, Rg6, and Rg7 are each independently selected from the group consisting of:
hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl;
R5 is selected from the group consisting of:
hydrogen, deuterium, C1-C6 alkyl, halogen, and amino;
or, R5 is selected from the group consisting of hydrogen and amino;
Y is C or S;
y is an integer of 0 or above;
or y is selected from the group consisting of 0, 1, 2, and 3;
or y is 0 or 1;
n is 0 or 1;
2) when x is 1 or 2, A and A′ are the same or different, wherein:
any one of R1, R2, R3, and R4 of a unit A is connected to any one of R1′, R2′, R3′, and R4′ of an adjacent unit A′ through L1;
each L1 is independently a unit-linking group selected from the group consisting of:
absence, O, S, carbonyl, alkyl (or C1-C6 alkyl), alkenyl (or C2-C6 alkenyl), alkynyl (or C2-C6 alkynyl), —O-alkenyl-O-(or —O-C2-C6 alkenyl-O—), —O-alkynyl-O-(or —O-C2-C6 alkynyl-O—), cycloalkyl (or C3-C7 cycloalkyl), and heteroalkyl (or 3- to 7-membered heteroalkyl;
for example, —O-alkyl-O-(or —O-C1-C6 alkyl-O—)), wherein the alkyl, cycloalkyl, heteroalkyl are optionally substituted with one or more groups independently selected from the group consisting of Z;
Z is independently selected from the group consisting of:
halogen, amino, alkyl (or C1-C6 alkyl), alkenyl (or C2-C6 alkenyl), alkynyl (or C2-C6 alkynyl), haloalkyl (or halogenated C1-C6 alkyl), cycloalkyl (or C3-C7 cycloalkyl), aryl (or C6-C12 aryl), and heterocyclyl;
or, L1 is selected from the group consisting of:
absence and —CR′R″, wherein R′ and R″ are each independently H, C1-C6 alkyl (or C1-C3 alkyl);
or, L1 is selected from the group consisting of:
absence, —CH2—, —CH(CH3)—, and —C—(CH3)2;
for A, wherein:
R1 and R2 are each independently selected from the group consisting of:
C1-C6 alkyl, —O—, —O—Ra1, and —NRa2Ra3;
R3 and R4 are each independently selected from the group consisting of:
hydrogen, deuterium, hydroxyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, —C(Rh)2—Rd1, —(CO)-(L)n-Rd2, —(CO)O-(L)n-Rd3, —(SO2)-(L)n-Rd4, and —P(O)(ORe)2, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, aryl (or C6-C12 aryl), and heterocyclyl;
Ra1, Ra2, and Ra3 are each independently selected from the group consisting of:
hydrogen, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, -(C1-C6 alkyl)n-(CO)—Rb1, -(C1-C6 alkyl)n-(CO)—O—Rb2, -(C1-C6 alkyl)n-O—(CO)—Rb3, -(C1-C6 alkyl)n-O—(CO)—O—Rb4, -(C1-C6 alkyl)n-(CO)—NRb5Rb6, -(C1-C6 alkyl)n-NRb7—(CO)—Rb8, and -(C1-C6 alkyl)n-NRb9—(CO)—O—Rb10, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, amino, hydroxyl, C1-C6 alkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, -(C1-C6 alkyl)-(C6-C10 aryl), and -(C1-C6 alkyl)-(3- to 15-membered heterocyclyl);
Rb1, Rb2, Rb3, Rb4, Rb5, Rb6, Rb7, Rb8, Rb9, Rb10 are each independently selected from the group consisting of:
hydrogen, deuterium, hydroxyl, amino, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, -(C1-C6 alkyl)n-(CO)—O—Rc1, -(C1-C6 alkyl)n-O—(CO)—Rc2, and -(C1-C6 alkyl)n-O—(CO)—O—Rc3, the alkyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, amino, hydroxyl, carboxyl, C1-C6 alkyl, and C6-C10 aryl;
Rc1, Rc2, and Rc3 are each independently selected from the group consisting of:
hydrogen, deuterium, hydroxyl, amino, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl;
L is each independently selected from the group consisting of:
absence, O, NRd5, C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl;
Re is each independently selected from the group consisting of hydrogen, deuterium, Na, K, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, C1-C6 alkyl, and halogenated C1-C6 alkyl;
Rh is each independently selected from the group consisting of:
C1-C6 alkyl, —NHC(O)Rg1, —OC(O)Rg2, —OP(O)(ONa)2, —NHC(O)ORd6, —OC(O)ORd7, and —OC(O)NHRd8;
Rd1, Rd2, Rd3, Rd4, Rd5, Rd6, Rd7, Rd8 are each independently selected from the group consisting of:
hydrogen, deuterium, amino, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more Rf groups;
Rf is each independently selected from the group consisting of halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C6-C10 aryl, halogenated C6-C10 aryl, C3-C7 cycloalkyl, 3- to 15-membered heterocyclyl, —NRg3Rg4, —ORg5, —NHC(O)Rg6, and —OC(O)Rg7;
Rg1, Rg2, Rg3, Rg4, Rg5, Rc6, and Rg7 are each independently selected from the group consisting of:
hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl;
R5 is selected from the group consisting of:
hydrogen, deuterium, C1-C6 alkyl, halogen, and amino;
or, R5 is selected from the group consisting of hydrogen and amino;
Y is C or S;
y is an integer of 0 or above;
or y is selected from the group consisting of 0, 1, 2 and 3;
or y is 0 or 1;
n is 0 or 1;
for A′, wherein:
R1′ and R2′ are each independently selected from the group consisting of:
C1-C6 alkyl, —O—, —O—Ra1, and —NRa2Ra3;
R3′ and R4′ are each independently selected from the group consisting of:
hydrogen, deuterium, hydroxyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, —C(Rh)2—Rd1, —(CO)-(L)n-Rd2, —(CO)O-(L)n-Rd3, —(SO2)-(L)n-Rd4, and —P(O)(ORe)2, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, aryl (or C6-C12 aryl), and heterocyclyl;
Ra1, Ra2, and Ra3 are each independently selected from the group consisting of:
hydrogen, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, -(C1-C6 alkyl)n-(CO)—Rb1, -(C1-C6 alkyl)n-(CO)—O—Rb2, -(C1-C6 alkyl)n-O—(CO)—Rb3, -(C1-C6 alkyl)n-O—(CO)—O—Rb4, -(C1-C6 alkyl)-(CO)—NRb5Rb6, -(C1-C6 alkyl)n-NRb7—(CO)—Rb8, and -(C1-C6 alkyl)n-NRb9—(CO)—O—Rb10, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, amino, hydroxyl, C1-C6 alkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, -(C1-C6 alkyl)-(C6-C10 aryl), and -(C1-C6 alkyl)-(3- to 15-membered heterocyclyl);
Rb1, Rb2, Rb3, Rb4, Rb5, Rb6, Rb7, Rb8, Rb9, Rb10 are each independently selected from the group consisting of:
hydrogen, deuterium, hydroxyl, amino, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, -(C1-C6 alkyl)-(CO)—O—Rc1, -(C1-C6 alkyl)n-O—(CO)—Rc2, and -(C1-C6 alkyl)n-O—(CO)—O—Rc3, the alkyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, amino, hydroxyl, carboxyl, C1-C6 alkyl, and C6-C10 aryl;
Rc1, Rc2, and Rc3 are each independently selected from the group consisting of:
hydrogen, deuterium, hydroxyl, amino, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl;
L is each independently selected from the group consisting of:
absence, O, NRd5, C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl;
Re is each independently selected from the group consisting of hydrogen, deuterium, Na, K, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, and heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, C1-C6 alkyl, and halogenated C1-C6 alkyl;
Rh is each independently selected from the group consisting of:
C1-C6 alkyl, —NHC(O)Rg1, —OC(O)Rg2, —OP(O)(ONa)2, —NHC(O)ORd6, —OC(O)ORd7, and —OC(O)NHRd8;
Rd1, Rd2, Rd3, Rd4, Rd5, Rd6, Rd7, Rd8 are each independently selected from the group consisting of:
hydrogen, deuterium, amino, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more R′ groups;
Rf is each independently selected from the group consisting of halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C6-C10 aryl, halogenated C6-C10 aryl, C3-C7 cycloalkyl, 3- to 15-membered heterocyclyl, —NRg3Rg4, —ORg5, —NHC(O)Rg6, and —OC(O)Rg7;
Rg1, Rg2, Rg3, Rg4, Rg5, Rg6, and Rg7 are each independently selected from the group consisting of:
hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl;
R5′ is selected from the group consisting of:
hydrogen, deuterium, C1-C6 alkyl, halogen, and amino;
or, R5 is selected from the group consisting of hydrogen and amino;
Y is C or S;
y′ is an integer of 0 and above;
or y′ is selected from the group consisting of 0, 1, 2, and 3;
or y′ is 0 or 1;
n is 0 or 1;
or, Formula I is:

107 more elements

Use of a compound represented by the following Formula I-4, or pharmaceutically acceptable salt, ester, prodrug, stereoisomer, hydrate, solvate, isotopic compound, crystalline form, metabolite form thereof, or any combination or mixture thereof, in the manufacture of a medicament or agent, wherein the medicament is used for at least one of the following:

1) treating, improving, or preventing a liver disease (e.g., NAFLD, NASH, liver fibrosis);
2) alleviating a mammalian liver fibrosis, liver steatosis, or inflammation;
3) inhibiting the activation of a stellate cell;
4) regulating the expression of NS3TP1;
wherein:
Rn1 and Rn2 are each independently selected from the group consisting of:
C1-C6 alkyl, —O—Ra4, —O-L2-O—Ra4, and —NRa5R36;
each Ra4 is independently selected from the group consisting of:
hydrogen, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl-C1-C6 alkyl, C6-C10 aryl, C6-C10 aryl-C1-C6 alkyl, 3- to 15-membered heterocyclyl, 3- to 15-membered heterocyclyl-C1-C6 alkyl, C1-C6 alkoxyacyl, —(O═)C—CH2—CH(NH2)—COORm;
(O═)C—CH(NH2)—CH2—COORm, Ph-CH2—CH(NH2)—C(═O)—, NH2-CH2—C(═O)—, CH3—CH(NH2)—C(═O)—, RmOOC—(CH2)2—CH(NH2)—C(═O)—, —C(═O)—(CH2)2—CH(NH2)—COORm, RmOOC—CH(NH2)—CH2—S—S—CH2—CH(NH2)—C(═O)—, H2N—CO—(CH2)2—CH(NH2)—C(═O)—, *N═CH—NH—CH═*C—CH2—CH(NH2)—C(═O)-(or
HO-p-Ph-CH2—CH(NH2)—C(═O)—, HO—CH2—CH(NH2)—C(═O)—, CH3—S—(CH2)2—CH(NH2)—C(═O)—, HN═C(NH2)—NH—(CH2)3—CH(NH2)—C(═O)—, and (CH3)2CH—CH2—CH(NH2)—C(═O)—;
wherein Ph represents phenyl, HO-p-Ph-CH2—CH(NH2)—C(═O)- represents p-hydroxybenzylaminomethylcarbonyl;
Ra5 and Ra6 are each independently selected from the group consisting of:
hydrogen, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, 3- to 15-membered heterocyclylaminoacyl-C1-C6 alkyl, Ph-CH2—CH(COORm)—, —CH2—COORm, —CH(COORm)—CH2—COORm;
—CH(CH3)—COORm;
RmOOC—(CH2)2—CH(COORm)—, —CH(COORm)—CH2—S—S—CH2—CH(NH2)—COORm;
H2N—CO—(CH2)2—CH(COORm)—, *N═CH—NH—CH═*C—CH2—CH(COORm)-(or
HO-p-Ph-CH2—CH(COORm)—, HO—CH2—CH(COORm)—, CH3—S—(CH2)2—CH(COORm)—, HN═C(NH2)—NH—(CH2)3—CH(COORm)—, and (CH3)2CH—CH2—CH(COORm)—;
each Rm is independently selected from the group consisting of:
hydrogen, C1-C6 alkyl, and C1-C6 alkoxyacyl-O-L3-;
L2 and L3 are each independently selected from the group consisting of:
C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, and 3- to 7-membered heteroalkyl, L2 and L3 are optionally substituted with one or more groups independently selected from the group consisting of halogen, amino, and hydroxyl;
Rn3 and Rn4 are each independently selected from the group consisting of:
hydrogen, deuterium, hydroxyl, H(C═O)—, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, aminoacyl, C1-C6 alkylacyl, C1-C6 alkoxyacyl, C1-C6 alkylaminoacyl, amino-C1-C6 alkanoyl, 3- to 15-membered heterocyclylacyl, C3-C7 cycloalkylacyl, and C6-C10 aryl-C1-C6 alkoxyacyl;
Y is C or S;
y is 0, 1, 2 or 3;
or
Rn1 and Rn2 are each independently selected from the group consisting of:
C1-C6 alkyl, —O—Ra4, —O-L2-O—Ra4, and —NRa5R86;
each Ra4 is independently selected from the group consisting of:
hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl-C1-C6 alkyl, C6-C10 aryl, C6-C10 aryl-C1-C6 alkyl, 3- to 15-membered heterocyclyl, 3- to 15-membered heterocyclyl-C1-C6 alkyl, C1-C6 alkoxyacyl, —(O═)C—CH2—CH(NH2)—COORm;
Ph-CH2—CH(NH2)—C(═O)—, NH2-CH2—C(═O)—, CH3—CH(NH2)—C(═O)—, RmOOC—(CH2)2—CH(NH2)—C(═O)—, RmOOC—CH(NH2)—CH2—S—S—CH2—CH(NH2)—C(═O)—, H2N—CO—(CH2)2—CH(NH2)—C(═O)—, *N═CH—NH—CH═*C—CH2—CH(NH2)—C(═O)-(or
HO-p-Ph-CH2—CH(NH2)—C(═O)—, HO—CH2—CH(NH2)—C(═O)—, CH3—S—(CH2)2—CH(NH2)—C(═O)—, HN═C(NH2)—NH—(CH2)3—CH(NH2)—C(═O)—, and (CH3)2CH—CH2—CH(NH2)—C(═O)—;
Ra5 and Ra6 are each independently selected from the group consisting of:
hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, 3- to 15-membered heterocyclylaminoacyl-C1-C6 alkyl, Ph-CH2—CH(COORm)—, —CH2—COORm, —CH(COORm)—CH2—COORm;
—CH(CH3)—COORm, RmOOC—(CH2)2—CH(COORm)—, —CH(COORm)—CH2—S—S—CH2—CH(NH2)—COORm, H2N—CO—(CH2)2—CH(COORm)—, *N═CH—NH—CH═*C—CH2—CH(COORm)-(or
HO-p-Ph-CH2—CH(COORm)—, HO—CH2—CH(COORm)—, CH3—S—(CH2)2—CH(COORm)—, HN═C(NH2)—NH—(CH2)3—CH(COORm)—, and (CH3)2CH—CH2—CH(COORm)—;
each Rm is independently selected from the group consisting of:
hydrogen, C1-C6 alkyl, and C1-C6 alkoxyacyl-O-L3-;
L2 and L3 are each independently selected from the group consisting of:
C1-C6 alkyl, C2-C6 alkenyl, C3-C7 cycloalkyl, and 3- to 7-membered heteroalkyl, L2 and L3 are each optionally substituted with one or more groups independently selected from the group consisting of halogen, amino, and hydroxyl;
Rn3 and Rn4 are each independently selected from the group consisting of:
hydrogen, hydroxyl, H(C—O)—, C1-C6 alkyl, C2-C6 alkenyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, aminoacyl, C1-C6 alkylacyl, C1-C6 alkoxyacyl, C1-C6 alkylaminoacyl, amino-C1-C6 alkanoyl, 3- to 15-membered heterocyclylacyl, C3-C7 cycloalkylacyl, and C6-C10 aryl-C1-C6 alkoxyacyl;
Y is C;
y is 0, 1 or 2;
or
Rn1 and Rn2 are each independently selected from the group consisting of:
C1-C6 alkyl, —O—Ra4, —O-L2-O—Ra4, and —NRa5R36;
each Ra4 is independently selected from the group consisting of:
hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C3-C7 cycloalkyl, C6-C10 aryl, C6-C10 aryl-C1-C6 alkyl, 3-15-membered heterocyclyl, 3- to 15-membered heterocyclyl-C1-C6 alkyl, —(O═)C—CH2—CH(NH2)—COORm;
Ph-CH2—CH(NH2)—C(═O)—, NH2-CH2—C(═O)—, CH3—CH(NH2)—C(═O)—, RmOOC—(CH2)2—CH(NH2)—C(═O)—, RmOOC—CH(NH2)—CH2—S—S—CH2—CH(NH2)—C(═O)—, H2N—CO—(CH2)2—CH(NH2)—C(═O)—, *N═CH—NH—CH═*C—CH2—CH(NH2)—C(═O)-(or
HO-p-Ph-CH2—CH(NH2)—C(═O)—, HO—CH2—CH(NH2)—C(═O)—, CH3—S—(CH2)2—CH(NH2)—C(═O)—, HN═C(NH2)—NH—(CH2)3—CH(NH2)—C(═O)—, and (CH3)2CH—CH2—CH(NH2)—C(═O)—;
Ra5 and Ra6 are each independently selected from the group consisting of:
hydrogen, C1-C6 alkyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, 3- to 15-membered heterocyclylaminoacyl-C1-C6 alkyl, Ph-CH2—CH(COORm)—, —CH2—COORm, —CH(COORm)—CH2—COORm, —CH(CH3)—COORm;
RmOOC—(CH2)2—CH(COORm)—, —CH(COORm)—CH2—S—S—CH2—CH(NH2)—COORm;
H2N—CO—(CH2)2—CH(COORm)—, *N═CH—NH—CH═*C—CH2—CH(COORm)-(or
HO-p-Ph-CH2—CH(COORm)—, HO—CH2—CH(COORm)—, CH3—S—(CH2)2—CH(COORm)—, HN═C(NH2)—NH—(CH2)3—CH(COORm)—, and (CH3)2CH—CH2—CH(COORm)—;
each Rm is independently selected from the group consisting of:
hydrogen, C1-C6 alkyl, and C1-C6 alkoxyacyl-O-L3-;
L2 and L3 are each independently selected from the group consisting of:
C1-C6 alkyl, L2 and L3 are each optionally substituted with one or more groups independently selected from the group consisting of halogen, amino, and hydroxyl;
Rn3 and Rn4 are each independently selected from the group consisting of:
hydrogen, hydroxyl, C1-C6 alkyl, C2-C6 alkenyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, aminoacyl, C1-C6 alkylacyl, C1-C6 alkoxyacyl, C1-C6 alkylaminoacyl, amino-C1-C6 alkanoyl, 3- to 15-membered heterocyclylacyl, C3-C7 cycloalkylacyl, and C6-C10 aryl-C1-C6 alkoxyacyl;
Y is C;
y is 0, 1 or 2.

62 more elements

Use of a peptide containing 2 to 10 or 2 to 3 amino acids, or pharmaceutically acceptable salt, ester, prodrug, stereoisomer, hydrate, solvate, isotopic compound, crystalline form, metabolite form thereof, or any combination or mixture thereof, in the manufacture of a medicament or agent,

wherein the drug or agent is used for at least one of the following:
1) treating, improving, or preventing a liver disease (e.g., NAFLD, NASH, liver fibrosis);
2) alleviating a mammalian liver fibrosis, liver steatosis, or inflammation;
3) inhibiting the activation of a stellate cell;
4) regulating the expression of NS3TP1;
in the peptide, at least one amino acid is aspartic acid, and when aspartic acid has a free carboxyl group, the free carboxyl group is optionally esterified with C1-C6 alkyl-OH;
optionally, the amino acid is aspartic acid, phenylalanine, glycine, alanine, glutamic acid, cystine, glutamine, histidine, tyrosine, serine, methionine, arginine acid or leucine;
or, the free amino acid located on one side of the peptide is aspartic acid, and optionally, the free carboxyl group of the free aspartic acid is optionally esterified with C1-C6 alkyl-OH;
optionally, the remaining amino acids are aspartic acid, phenylalanine, glycine, alanine, glutamic acid, cystine, glutamine, histidine, tyrosine, serine, methionine, arginine or leucine.

6 more elements

A compound represented by Formula II, or pharmaceutically acceptable salt or ester, prodrug, stereoisomer, hydrate, solvate, crystalline form, and metabolism form thereof,

A1-(L1)x-A1′ Formula II
wherein, A1 is
A1 and A1′ are the same or different
x is selected from the group consisting of 0, 1 and 2;
1) when x is 0, A′ is absent;
for A1, wherein:
R1 and R2 are independently selected from the group consisting of:
and —O—Ra,
Ra is each independently selected from the group consisting of:
hydrogen, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, -(C1-C6 alkyl)n-(CO)—Rb1, -(C1-C6 alkyl)n-(CO)—O—Rb2, -(C1-C6 alkyl)n-O—(CO)—Rb3, -(C1-C6 alkyl)n-NRb4—(CO)—Rb5, and -(C1-C6 alkyl)n-NRb6—(CO)—O—Rb7, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, and heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, amino, hydroxyl, C1-C6 alkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, -(C1-C6 alkyl)-(C6-C10 aryl), and (C1-C6 alkyl)-(3- to 15-membered heterocyclyl);
Rb1, Rb2, Rb3, Rb4, Rb5, Rb6, Rb7 are each independently selected from the group consisting of:
hydrogen, deuterium, hydroxyl, amino, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl;
R3 and R4 are independently selected from the group consisting of:
—COCH(CH3)(NH2), hydrogen, —COCH2CH3, deuterium, and C1-C6 alkyl, the alkyl is optionally substituted with one or more groups independently selected from the group consisting of halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, aryl, and heterocyclyl;
and for “x is 0, A′ is absent”, A1 meets one of the following conditions, (1), (2), (3) or (4):
(1) at least one of R1 and R2 is
(2) at least one of R3 and R4 is-COCH(CH3)(NH2) or —COCH2CH3;
(3) when the situation is:
R1 and R2 are independently selected from the group consisting of:
hydroxyl, methoxy, and at the same time, R3 and R4 are independently selected from the group consisting of:
hydrogen, —COCH2CH3 and —COCH(CH3)(NH2),
A1 meets the following conditions:
when one of R1 and R2 is hydroxyl or methoxy, the other of R1 and R2 is
or one of R3 and R4 is-COCH(CH3)(NH2);
(4) when the situation is:
R1 is selected from the group consisting of:
hydroxyl, methoxy,
R2 is selected from the group consisting of:
hydroxyl,
methoxy,
and at the same time, R3 and R4 are independently selected from the group consisting of:
hydrogen, —COCH2CH3 and —COCH(CH3)(NH2),
A1 meets the following conditions:
when R1 is hydroxyl or methoxy, R2 is
or one of R3 and R4 is-COCH(CH3)(NH2), or
when R2 is hydroxyl or methoxy, R1 is
or one of R3 and R4 is —COCH(CH3)(NH2);
2. when x is 1, A1 and A1′ are the same or different, wherein
any one of R1, R2, R3, and R4 of a unit A1 is connected to any one of R1′, R2′, R3′ and R4′ of an adjacent unit A1′ through L1;
each L1 is independently a unit-linking group selected from the group consisting of:
absence, O, S, carbonyl, alkyl (or C1-C6 alkyl), alkenyl (or C2-C6 alkenyl), alkynyl (or C2-C6 alkynyl), —O-alkyl-O-(or —O-C1-C6 alkyl-O—), —O-alkenyl-O-(or —O-C2-C6 alkenyl-O—), —O-alkynyl-O-(or —O-C2-C6 alkynyl-O—), cycloalkyl (or C3-C7 cycloalkyl), and heteroalkyl (or 3- to 7-membered heteroalkyl), wherein the alkyl, cycloalkyl, heteroalkyl are optionally substituted with one or more groups independently selected from the group consisting of Z;
Z is independently selected from the group consisting of:
halogen, amino, alkyl (or C1-C6 alkyl), alkenyl (or C2-C6 alkenyl), alkynyl (or C2-C6 alkynyl), haloalkyl (or halogenated C1-C6 alkyl), cycloalkyl (or C3-C7 cycloalkyl), aryl (or C6-C12 aryl), and heterocyclyl;
or, L1 is selected from the group consisting of:
absence and —CR′R″, wherein R′ and R″ are each independently H, C1-C6 alkyl (or C1-C3 alkyl);
or, L1 is selected from the group consisting of:
absence, —CH2—, —CH(CH3)—, and —C—(CH3)2;
for A1, wherein:
R1 and R2 are each independently selected from the group consisting of:
C1-C6 alkyl, —O—, —O—Ra1, and —NRa2Ra3;
R3 and R4 are each independently selected from the group consisting of:
hydrogen, deuterium, hydroxyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, aryl (or C6-C12 aryl), and heterocyclyl;
Ra1, Ra2, and Ra3 are each independently selected from the group consisting of:
hydrogen, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, amino, hydroxyl, C1-C6 alkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, (C1-C6 alkyl)-(C6-C10 aryl), and -(C1-C6 alkyl)-(3- to 15-membered heterocyclyl);
or, R1 is selected from the group consisting of:
—O—, C1-C6 alkyl, and —O—Ra1, wherein Ra1 is selected from the group consisting of:
hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, and -(C1-C6 alkyl)n-O—(CO)—Rb1, the alkyl, alkenyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, amino, hydroxyl, C1-C6 alkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, -(C1-C6 alkyl)-(C6-C10 aryl), and -(C1-C6 alkyl)-(3- to 15-membered heterocyclyl);
or, R1 is selected from the group consisting of:
—O—, hydroxyl, and —O—Ra:
Ra is C1-C6 alkyl;
or, R1 is selected from the group consisting of:
—O—, hydroxyl, methoxy, ethoxy, and —OCH(CH3)2;
or, R2 is selected from the group consisting of:
—O—, C1-C6 alkyl, and —O—Ra1, wherein Ra1 is selected from the group consisting of:
hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, and -(C1-C6 alkyl)n-O—(CO)—Rb1, the alkyl, alkenyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, amino, hydroxyl, C1-C6 alkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, -(C1-C6 alkyl)-(C6-C10 aryl), and -(C1-C6 alkyl)-(3- to 15-membered heterocyclyl);
or, R2 is selected from the group consisting of:
hydroxyl, —O—, and —O—Ra:
Ra is C1-C6 alkyl;
or, R2 is selected from the group consisting of:
hydroxyl, —O—, and methoxy, R3 and R4 are each independently selected from the group consisting of:
hydrogen, hydroxyl, and C1-C6 alkyl;
or, R3 and R4 are each independently hydrogen;
R5 is selected from the group consisting of:
hydrogen, deuterium, C1-C6 alkyl, halogen, and amino;
or, R5 is selected from the group consisting of hydrogen and amino;
or, R5 is selected from the group consisting of hydrogen;
Y is C;
y is selected from the group consisting of 0, 1, 2, and 3;
or y is 0 or 1;
or y is 0;
for A1′, wherein:
R1′ and R2′ are each independently selected from the group consisting of:
C1-C6 alkyl, —O—, —O—Ra1, and —NRa2Ra3;
R3′ and R4′ are each independently selected from the group consisting of:
hydrogen, deuterium, hydroxyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, aryl (or C6-C12 aryl) and heterocyclyl;
Ra1, Ra2, and Ra3 are each independently selected from the group consisting of:
hydrogen, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, amino, hydroxyl, C1-C6 alkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, (C1-C6 alkyl)-(C6-C10 aryl), and -(C1-C6 alkyl)-(3- to 15-membered heterocyclyl);
or, R1′ is selected from the group consisting of:
—O—, C1-C6 alkyl, and —O—Ra1, wherein Ra1 is selected from the group consisting of:
hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, and -(C1-C6 alkyl)n-O—(CO)—Rb1, the alkyl, alkenyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, amino, hydroxyl, C1-C6 alkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, -(C1-C6 alkyl)-(C6-C10 aryl), and -(C1-C6 alkyl)-(3- to 15-membered heterocyclyl);
or, R1′ is selected from the group consisting of:
—O—, hydroxyl, and —O—Ra:
Ra is C1-C6 alkyl;
or, R1′ is selected from the group consisting of:
—O—, hydroxyl, methoxy, ethoxy, and —OCH(CH3)2;
or, R2′ is selected from the group consisting of:
—O—, C1-C6 alkyl, and —O—Ra1, wherein Ra1 is selected from the group consisting of:
hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, and -(C1-C6 alkyl)n-O—(CO)—Rb1, the alkyl, alkenyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, amino, hydroxyl, C1-C6 alkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, -(C1-C6 alkyl)-(C6-C10 aryl), and -(C1-C6 alkyl)-(3- to 15-membered heterocyclyl);
or, R2′ is selected from the group consisting of:
hydroxyl, —O—, and —O—Ra:
Ra is C1-C6 alkyl;
or, R2′ is selected from the group consisting of:
hydroxyl, —O—, and methoxy;
R3′ and R4′ are each independently selected from the group consisting of:
hydrogen, hydroxyl, and C1-C6 alkyl;
or, R3′ and R4′ are each independently hydrogen;
R5′ is selected from the group consisting of:
hydrogen, deuterium, C1-C6 alkyl, halogen, and amino;
or, R5′ is selected from the group consisting of hydrogen and amino;
or, R5′ is selected from the group consisting of hydrogen;
Y′ is C;
y′ is selected from the group consisting of 0, 1, 2, and 3;
or y is 0 or 1;
or y′ is 0;
3. when x is 2, A1 and A1′ are the same or different, wherein
any one of R1, R2, R3 and R4 of a unit A1 is connected to any one of R1′, R2′, R3′ and R4′ of an adjacent unit A1′ through L1;
each L1 is independently a unit-linking group selected from the group consisting of:
absence, O, S, carbonyl, alkyl (or C1-C6 alkyl), alkenyl (or C2-C6 alkenyl), alkynyl (or C2-C6 alkynyl), —O-alkyl-O-(or —O-C1-C6 alkyl-O—), —O-alkenyl-O-(or —O-C2-C6 alkenyl-O—), —O-alkynyl-O-(or —O-C2-C6 alkynyl-O—), cycloalkyl (or C3-C7 cycloalkyl), and heteroalkyl (or 3- to 7-membered heteroalkyl), wherein the alkyl, cycloalkyl, heteroalkyl are optionally substituted with one or more groups independently selected from the group consisting of Z;
Z is independently selected from the group consisting of:
halogen, amino, alkyl (or C1-C6 alkyl), alkenyl (or C2-C6 alkenyl), alkynyl (or C2-C6 alkynyl), haloalkyl (or halogenated C1-C6 alkyl), cycloalkyl (or C3-C7 cycloalkyl), aryl (or C6-C12 aryl), and heterocyclyl;
or, L1 is selected from the group consisting of:
absence and —CR′R″, wherein R′and R″ are each independently H, C1-C6 alkyl (or C1-C3 alkyl);
or, L1 is selected from the group consisting of:
absence, —CH2—, —CH(CH3)—, and —C—(CH3)2;
or, L1 is selected from the group consisting of:
—CH2—;
for A1, wherein:
R1 and R2 are each independently selected from the group consisting of:
C1-C6 alkyl, —O—, —O—Ra1, and —NRa2Ra3;
R3 and R4 are each independently selected from the group consisting of:
hydrogen, deuterium, hydroxyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, aryl (or C6-C12 aryl), and heterocyclyl;
Ra1, Ra2, and Ra3 are each independently selected from the group consisting of:
hydrogen, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, amino, hydroxyl, C1-C6 alkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, (C1-C6 alkyl)-(C6-C10 aryl), and -(C1-C6 alkyl)-(3- to 15-membered heterocyclyl);
or, R1 is selected from the group consisting of:
—O—, C1-C6 alkyl, and —O—Ra1, wherein Ra1 is selected from the group consisting of:
hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, and -(C1-C6 alkyl)n-O—(CO)—Rb1, the alkyl, alkenyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, amino, hydroxyl, C1-C6 alkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, -(C1-C6 alkyl)-(C6-C10 aryl), and -(C1-C6 alkyl)-(3- to 15-membered heterocyclyl);
or, R1 is selected from the group consisting of:
—O—, hydroxyl, and —O—Ra;
Ra is C1-C6 alkyl;
or, R1 is selected from the group consisting of:
—O—, hydroxyl, methoxy, ethoxy, and —OCH(CH3)2;
or, R1 is selected from the group consisting of:
methoxy;
or, R2 is selected from the group consisting of:
—O—, C1-C6 alkyl, and —O—Ra1, wherein Ra1 is selected from the group consisting of:
hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, and -(C1-C6 alkyl)n-O—(CO)—Rb1, the alkyl, alkenyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, amino, hydroxyl, C1-C6 alkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, -(C1-C6 alkyl)-(C6-C10 aryl), and -(C1-C6 alkyl)-(3- to 15-membered heterocyclyl);
or, R2 is selected from the group consisting of:
hydroxyl, —O—, and —O—Ra;
Ra is C1-C6 alkyl;
or, R2 is selected from the group consisting of:
hydroxyl, —O—, and methoxy,
or, R2 is selected from the group consisting of:
—O—;
R3 and R4 are each independently selected from the group consisting of:
hydrogen, hydroxyl, and C1-C6 alkyl;
or, R3 and R4 are each independently hydrogen;
R5 is selected from the group consisting of:
hydrogen, deuterium, C1-C6 alkyl, halogen, and amino;
or, R5 is selected from the group consisting of hydrogen and amino;
or, R5 is selected from the group consisting of hydrogen;
Y is C;
y is selected from the group consisting of 0, 1, 2, and 3;
or y is 0 or 1;
or y is 0;
for A1′, wherein:
R1′ and R2′ are each independently selected from the group consisting of:
C1-C6 alkyl, —O—, —O—Ra1, and —NRa2Ra3;
R3′ and R4′ are each independently selected from the group consisting of:
hydrogen, deuterium, hydroxyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, aryl (or C6-C12 aryl) and heterocyclyl;
Ra1, Ra2, and Ra3 are each independently selected from the group consisting of:
hydrogen, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, amino, hydroxyl, C1-C6 alkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, (C1-C6 alkyl)-(C6-C10 aryl), and -(C1-C6 alkyl)-(3- to 15-membered heterocyclyl);
or, R1′ is selected from the group consisting of:
—O—, C1-C6 alkyl, and —O—Ra1, wherein Ra1 is selected from the group consisting of:
hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, and -(C1-C6 alkyl)n-O—(CO)—Rb1, the alkyl, alkenyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, amino, hydroxyl, C1-C6 alkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, -(C1-C6 alkyl)-(C6-C10 aryl), and -(C1-C6 alkyl)-(3- to 15-membered heterocyclyl);
or, R1′ is selected from the group consisting of:
—O—, hydroxyl, and —O—Ra:
Ra is C1-C6 alkyl;
or, R1′ is selected from the group consisting of:
—O—, hydroxyl, methoxy, ethoxy, and —OCH(CH3)2;
or, R1′ is selected from the group consisting of:
methoxy;
or, R2′ is selected from the group consisting of:
—O—, C1-C6 alkyl, and —O—Ra1, wherein Ra1 is selected from the group consisting of:
hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, and -(C1-C6 alkyl)n-O—(CO)—Rb1, the alkyl, alkenyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, amino, hydroxyl, C1-C6 alkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, -(C1-C6 alkyl)-(C6-C10 aryl), and -(C1-C6 alkyl)-(3- to 15-membered heterocyclyl);
or, R2′ is selected from the group consisting of:
hydroxyl, —O—, and —O—Ra:
Ra is C1-C6 alkyl;
or, R2′ is selected from the group consisting of:
hydroxyl, —O—, and methoxy;
or, R2′ is selected from the group consisting of:
—O—;
R3′ and R4′ are each independently selected from the group consisting of:
hydrogen, hydroxyl, and C1-C6 alkyl;
or, R3′ and R4′ are each independently hydrogen;
R5′ is selected from the group consisting of:
hydrogen, deuterium, C1-C6 alkyl, halogen, and amino;
or, R5′ is selected from the group consisting of hydrogen and amino;
or, R5′ is selected from the group consisting of hydrogen;
Y′ is C;
y′ is selected from the group consisting of 0, 1, 2, and 3;
or y is 0 or 1;
or y′ is 0;
or, Formula II is:

200 more elements

Dependencies are inferred from the claim text.

Facts

Application: 18/706,837Filed 11 Nov 2022
Priority: CN 202111341140.112 Nov 2021
Published: 23 Jan 2025
Term ends: Not estimatedThe source records don’t support an estimate.

Classification22 codes

A61K 31/225
Of acyclic acids, e.g. pravastatin: polycarboxylic acids
A61P 1/06
Drugs for disorders of the alimentary tract or the digestive system: anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
A61K 31/198
The amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine,…:…
A61K 31/215
Esters, e.g. nitroglycerine, selenocyanates: of carboxylic acids

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Abstract

1) treating, improving, or preventing a liver disease (e.g., NAFLD, NASH, liver fibrosis);
2) alleviating a mammalian liver fibrosis, liver steatosis, or inflammation;
3) inhibiting the activation of stellate cells;
4) regulating the expression of NS3TP1;
A-(L1)x-A′ (Formula I)
wherein, A is
A′ is
A and A′ are the same or different;
wherein:
x is selected from the group consisting of 0, 1 and 2;
1) when x is 0, A′ is absent;
for A, wherein:
R1 and R2 are each independently selected from the group consisting of:
C1-C6 alkyl, —O—Ra1, and —NRa2Ra3;
R3 and R4 are each independently selected from the group consisting of:
hydrogen, deuterium, hydroxyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, —C(Rh)2—Rd1, —(CO)-(L)n-Rd2, —(CO)O-(L)n-Rd3, —(SO2)-(L)n-Rd4, and —P(O)(ORe)2, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, aryl (or C6-C12 aryl), and heterocyclyl;
Ra1, Ra2, and Ra3 are each independently selected from the group consisting of:
hydrogen, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, -(C1-C6 alkyl)n-(CO)—Rb1, -(C1-C6 alkyl)n-(CO)—O—Rb2, -(C1-C6 alkyl)n-O—(CO)—Rb3, -(C1-C6 alkyl)n-O—(CO)—O—Rb4, -(C1-C6 alkyl)n-(CO)—NRb5Rb6, -(C1-C6 alkyl)n-NRb7—(CO)—Rb8, and -(C1-C6 alkyl)n-NRb9—(CO)—O—Rb10, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, amino, hydroxyl, C1-C6 alkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, -(C1-C6 alkyl)-(C6-C10 aryl), and -(C1-C6 alkyl)-(3- to 15-membered heterocyclyl);
Rb1, Rb2, Rb3, Rb4, Rb5, Rb6, Rb7, Rb8, Rb9, Rb10 are each independently selected from the group consisting of:
hydrogen, deuterium, hydroxyl, amino, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, -(C1-C6 alkyl)n-(CO)—O—Rc1, -(C1-C6 alkyl)n-O—(CO)—Rc2, and -(C1-C6 alkyl)n-O—(CO)—O—Rc3, the alkyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, amino, hydroxyl, carboxyl, C1-C6 alkyl, and C6-C10 aryl;
Rc1, Rc2, and Rc3 are each independently selected from the group consisting of:
hydrogen, deuterium, hydroxyl, amino, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl;
L is each independently selected from the group consisting of:
absence, O, NRd5, C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl;
Re is each independently selected from the group consisting of hydrogen, deuterium, Na, K, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, C1-C6 alkyl, and halogenated C1-C6 alkyl;
Rh is each independently selected from the group consisting of:
C1-C6 alkyl, —NHC(O)Rg1, —OC(O)Rg2, —OP(O)(ONa)2, —NHC(O)ORd6, —OC(O)ORd7, and —OC(O)NHRd8;
Rd1, Rd2, Rd3, Rd4, Rd5, Rd6, Rd7, Rd8 are each independently selected from the group consisting of:
hydrogen, deuterium, amino, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more Rf groups;
Rf is each independently selected from the group consisting of halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C6-C10 aryl, halogenated C6-C10 aryl, C3-C7 cycloalkyl, 3- to 15-membered heterocyclyl, —NRg3Rg4, —ORg5, —NHC(O)Rg6, and —OC(O)Rg7;
Rg1, Rg2, Rg3, Rg4, Rg5, Rg6, and Rg7 are each independently selected from the group consisting of:
hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl;
R5 is selected from the group consisting of:
hydrogen, deuterium, C1-C6 alkyl, halogen, and amino;
or, R5 is selected from the group consisting of hydrogen and amino;
Y is C or S;
y is an integer of 0 or above;
or y is selected from the group consisting of 0, 1, 2, and 3;
or y is 0 or 1;
n is 0 or 1;
2) when x is 1 or 2, A and A′ are the same or different, wherein:
any one of R1, R2, R3, and R4 of a unit A is connected to any one of R1′, R2′, R3′, and R4′ of an adjacent unit A′ through L1;
each L1 is independently a unit-linking group selected from the group consisting of:
absence, O, S, carbonyl, alkyl (or C1-C6 alkyl), alkenyl (or C2-C6 alkenyl), alkynyl (or C2-C6 alkynyl), —O-alkenyl-O-(or —O-C2-C6 alkenyl-O—), —O-alkynyl-O-(or —O-C2-C6 alkynyl-O—), cycloalkyl (or C3-C7 cycloalkyl), and heteroalkyl (or 3- to 7-membered heteroalkyl;
for example, —O-alkyl-O-(or —O-C1-C6 alkyl-O—)), wherein the alkyl, cycloalkyl, heteroalkyl are optionally substituted with one or more groups independently selected from the group consisting of Z;
Z is independently selected from the group consisting of:
halogen, amino, alkyl (or C1-C6 alkyl), alkenyl (or C2-C6 alkenyl), alkynyl (or C2-C6 alkynyl), haloalkyl (or halogenated C1-C6 alkyl), cycloalkyl (or C3-C7 cycloalkyl), aryl (or C6-C12 aryl), and heterocyclyl;
or, L1 is selected from the group consisting of:
absence and —CR′R″, wherein R′ and R″ are each independently H, C1-C6 alkyl (or C1-C3 alkyl);
or, L1 is selected from the group consisting of:
absence, —CH2—, —CH(CH3)—, and —C—(CH3)2;
for A, wherein:
R1 and R2 are each independently selected from the group consisting of:
C1-C6 alkyl, —O—, —O—Ra1, and —NRa2Ra3;
R3 and R4 are each independently selected from the group consisting of:
hydrogen, deuterium, hydroxyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, —C(Rh)2—Rd1, —(CO)-(L)n-Rd2, —(CO)O-(L)n-Rd3, —(SO2)-(L)n-Rd4, and —P(O)(ORe)2, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, aryl (or C6-C12 aryl), and heterocyclyl;
Ra1, Ra2, and Ra3 are each independently selected from the group consisting of:
hydrogen, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, -(C1-C6 alkyl)n-(CO)—Rb1, -(C1-C6 alkyl)n-(CO)—O—Rb2, -(C1-C6 alkyl)n-O—(CO)—Rb3, -(C1-C6 alkyl)n-O—(CO)—O—Rb4, -(C1-C6 alkyl)n-(CO)—NRb5Rb6, -(C1-C6 alkyl)n-NRb7—(CO)—Rb8, and -(C1-C6 alkyl)n-NRb9—(CO)—O—Rb10, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, amino, hydroxyl, C1-C6 alkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, -(C1-C6 alkyl)-(C6-C10 aryl), and -(C1-C6 alkyl)-(3- to 15-membered heterocyclyl);
Rb1, Rb2, Rb3, Rb4, Rb5, Rb6, Rb7, Rb8, Rb9, Rb10 are each independently selected from the group consisting of:
hydrogen, deuterium, hydroxyl, amino, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, -(C1-C6 alkyl)n-(CO)—O—Rc1, -(C1-C6 alkyl)n-O—(CO)—Rc2, and -(C1-C6 alkyl)n-O—(CO)—O—Rc3, the alkyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, amino, hydroxyl, carboxyl, C1-C6 alkyl, and C6-C10 aryl;
Rc1, Rc2, and Rc3 are each independently selected from the group consisting of:
hydrogen, deuterium, hydroxyl, amino, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl;
L is each independently selected from the group consisting of:
absence, O, NRd5, C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl;
Re is each independently selected from the group consisting of hydrogen, deuterium, Na, K, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, C1-C6 alkyl, and halogenated C1-C6 alkyl;
Rh is each independently selected from the group consisting of:
C1-C6 alkyl, —NHC(O)Rg1, —OC(O)Rg2, —OP(O)(ONa)2, —NHC(O)ORd6, —OC(O)ORd7, and —OC(O)NHRd8;
Rd1, Rd2, Rd3, Rd4, Rd5, Rd6, Rd7, Rd8 are each independently selected from the group consisting of:
hydrogen, deuterium, amino, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more Rf groups;
Rf is each independently selected from the group consisting of halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C6-C10 aryl, halogenated C6-C10 aryl, C3-C7 cycloalkyl, 3- to 15-membered heterocyclyl, —NRg3Rg4, —ORg5, —NHC(O)Rg6, and —OC(O)Rg7;
Rg1, Rg2, Rg3, Rg4, Rg5, Rc6, and Rg7 are each independently selected from the group consisting of:
hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl;
R5 is selected from the group consisting of:
hydrogen, deuterium, C1-C6 alkyl, halogen, and amino;
or, R5 is selected from the group consisting of hydrogen and amino;
Y is C or S;
y is an integer of 0 or above;
or y is selected from the group consisting of 0, 1, 2 and 3;
or y is 0 or 1;
n is 0 or 1;
for A′, wherein:
R1′ and R2′ are each independently selected from the group consisting of:
C1-C6 alkyl, —O—, —O—Ra1, and —NRa2Ra3;
R3′ and R4′ are each independently selected from the group consisting of:
hydrogen, deuterium, hydroxyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, —C(Rh)2—Rd1, —(CO)-(L)n-Rd2, —(CO)O-(L)n-Rd3, —(SO2)-(L)n-Rd4, and —P(O)(ORe)2, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, aryl (or C6-C12 aryl), and heterocyclyl;
Ra1, Ra2, and Ra3 are each independently selected from the group consisting of:
hydrogen, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, -(C1-C6 alkyl)n-(CO)—Rb1, -(C1-C6 alkyl)n-(CO)—O—Rb2, -(C1-C6 alkyl)n-O—(CO)—Rb3, -(C1-C6 alkyl)n-O—(CO)—O—Rb4, -(C1-C6 alkyl)-(CO)—NRb5Rb6, -(C1-C6 alkyl)n-NRb7—(CO)—Rb8, and -(C1-C6 alkyl)n-NRb9—(CO)—O—Rb10, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, amino, hydroxyl, C1-C6 alkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, -(C1-C6 alkyl)-(C6-C10 aryl), and -(C1-C6 alkyl)-(3- to 15-membered heterocyclyl);
Rb1, Rb2, Rb3, Rb4, Rb5, Rb6, Rb7, Rb8, Rb9, Rb10 are each independently selected from the group consisting of:
hydrogen, deuterium, hydroxyl, amino, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, 3- to 15-membered heterocyclyl, -(C1-C6 alkyl)-(CO)—O—Rc1, -(C1-C6 alkyl)n-O—(CO)—Rc2, and -(C1-C6 alkyl)n-O—(CO)—O—Rc3, the alkyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, amino, hydroxyl, carboxyl, C1-C6 alkyl, and C6-C10 aryl;
Rc1, Rc2, and Rc3 are each independently selected from the group consisting of:
hydrogen, deuterium, hydroxyl, amino, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl;
L is each independently selected from the group consisting of:
absence, O, NRd5, C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl;
Re is each independently selected from the group consisting of hydrogen, deuterium, Na, K, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, and heterocyclyl are optionally substituted with one or more groups independently selected from the group consisting of halogen, C1-C6 alkyl, and halogenated C1-C6 alkyl;
Rh is each independently selected from the group consisting of:
C1-C6 alkyl, —NHC(O)Rg1, —OC(O)Rg2, —OP(O)(ONa)2, —NHC(O)ORd6, —OC(O)ORd7, and —OC(O)NHRd8;
Rd1, Rd2, Rd3, Rd4, Rd5, Rd6, Rd7, Rd8 are each independently selected from the group consisting of:
hydrogen, deuterium, amino, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl are optionally substituted with one or more R′ groups;
Rf is each independently selected from the group consisting of halogen, C1-C6 alkyl, halogenated C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C6-C10 aryl, halogenated C6-C10 aryl, C3-C7 cycloalkyl, 3- to 15-membered heterocyclyl, —NRg3Rg4, —ORg5, —NHC(O)Rg6, and —OC(O)Rg7;
Rg1, Rg2, Rg3, Rg4, Rg5, Rg6, and Rg7 are each independently selected from the group consisting of:
hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C6-C10 aryl, and 3- to 15-membered heterocyclyl;
R5′ is selected from the group consisting of:
hydrogen, deuterium, C1-C6 alkyl, halogen, and amino;
or, R5 is selected from the group consisting of hydrogen and amino;
Y is C or S;
y′ is an integer of 0 and above;
or y′ is selected from the group consisting of 0, 1, 2, and 3;
or y′ is 0 or 1;
n is 0 or 1;
or, Formula I is:

107 more elements

Facts

Application

18/706,837Filed 11 Nov 2022

Priority

CN 202111341140.112 Nov 2021

Published

23 Jan 2025

Term ends

Not estimatedThe source records don’t support an estimate.

Classification22 codes

A61K 31/225
Of acyclic acids, e.g. pravastatin: polycarboxylic acids
A61P 1/06
Drugs for disorders of the alimentary tract or the digestive system: anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
A61K 31/198
The amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine,…:…
A61K 31/215
Esters, e.g. nitroglycerine, selenocyanates: of carboxylic acids