Back to results
US 11,111,249 B2Granted
Heteroaryl-pyrazole derivative, and preparation method therefor and medical application thereof
AssigneesJiangsu Hengrui Medicine Co., Ltd., Shanghai Hengrui Pharmaceutical Co., Ltd.
InventorsGuobao Zhang, Dianqiang Ma, Huiqing Yuan, Feng He, Weikang Tao
Life of this patent
Estimating the term…
Abstract
A heteroaryl-pyrazole derivative, and a preparation method therefor and a medical application thereof are described. Specifically, a new heteroaryl-pyrazole derivative as shown in formula (I), a preparation method for the derivative, a pharmaceutical composition containing the derivative, and a use of the derivative as a therapeutic agent, in particular as a TLR7 agonist, are described. The substituents in formula (I) have the same definitions as in the description.
Claims15
A compound of formula (I):
- or a tautomer, a mesomer, a racemate, an enantiomer, a diastereomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof,
- wherein,
- ring A is selected from the group consisting of cycloalkyl, aryl and heteroaryl;
- G is N or CR4;
- L1 is selected from the group consisting of —NR5—, —O—, —C(O)—, —S(O)m—, —N(R5)C(O)—, —C(O)N(R5)—, —N(R5)S(O)2—, —S(O)2N(R5)— and a covalent bond;
- R1 is selected from the group consisting of hydrogen atom, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is independently and optionally substituted by one or more substituents selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclyl, aryl and heteroaryl;
- each R2 is identical or different, and each is independently selected from the group consisting of hydrogen atom, halogen, alkyl, alkoxy, haloalkyl, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclyl, aryl, heteroaryl, —C(O)R6, —C(O)OR6, —S(O)mR6, —NR7R8 and —C(O)NR7R8, wherein each of the alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is independently and optionally substituted by one or more substituents selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclyl, aryl and heteroaryl;
- L2 is alkylene or a covalent bond, wherein the alkylene is optionally substituted by one or more substituents selected from the group consisting of halogen, alkyl, alkoxy, haloalkyl, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl and heterocyclyl;
- R3 is selected from the group consisting of hydrogen atom, alkyl, alkoxy, halogen, haloalkyl, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclyl, aryl, heteroaryl, —C(O)R6, —C(O)OR6, —S(O)mR6, —NR7R8 and —C(O)NR7R8, wherein each of the cycloalkyl, heterocyclyl, aryl and heteroaryl is independently and optionally substituted by one or more substituents selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclyl, aryl, heteroaryl, —C(O)R6, —C(O)OR6, —S(O)mR6, —NR7R8 and —C(O)NR7R8;
- Ra and Rb are identical or different, and each is independently selected from the group consisting of hydrogen atom, halogen, alkyl, alkoxy, haloalkyl, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclyl, aryl and heteroaryl;
- R4 is selected from the group consisting of hydrogen atom, halogen, alkyl, alkoxy, haloalkyl, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclyl, aryl and heteroaryl;
- R5 is selected from the group consisting of hydrogen atom, alkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
- R6 is selected from the group consisting of hydrogen atom, alkyl, haloalkyl, amino, hydroxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
- R7 and R8 are identical or different, and each is independently selected from the group consisting of hydrogen atom, alkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein each of the alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is independently and optionally substituted by one or more substituents selected from the group consisting of alkyl, alkoxy, halogen, amino, cyano, nitro, hydroxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
- or, R7 and R8 are linked together with the attached nitrogen atom to form heterocyclyl, wherein, except the one nitrogen atom, the heterocyclyl contains one or two identical or different heteroatoms selected from the group consisting of N, O and S, and the heterocyclyl is optionally substituted by one or more substituents selected from the group consisting of alkyl, alkoxy, halogen, amino, cyano, nitro, hydroxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
- n is 0, 1, 2, 3 or 4;
- and
- m is 0, 1 or 2.
15 more elements
A compound of formula:
A compound of formula (IA):
- or a tautomer, a mesomer, a racemate, an enantiomer, a diastereomer thereof, or a mixture thereof, or a pharmaceutically acceptable salt thereof,
- wherein,
- W is amino protecting group;
- ring A is selected from the group consisting of cycloalkyl, aryl and heteroaryl;
- G is N or CR4;
- L1 is selected from the group consisting of —NR5—, —O—, —C(O)—, —S(O)m—, —N(R5)C(O)—, —C(O)N(R5)—, —N(R5)S(O)2—, —S(O)2N(R5)— and a covalent bond;
- R1 is selected from the group consisting of hydrogen atom, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is independently and optionally substituted by one or more substituents selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclyl, aryl and heteroaryl;
- each R2 is identical or different, and each is independently selected from the group consisting of hydrogen atom, halogen, alkyl, alkoxy, haloalkyl, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclyl, aryl, heteroaryl, —C(O)R6, —C(O)OR6, —S(O)mR6, —NR7R8 and —C(O)NR7R8, wherein each of the alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is independently and optionally substituted by one or more substituents selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclyl, aryl and heteroaryl;
- L2 is alkylene or a covalent bond, wherein the alkylene is optionally substituted by one or more substituents selected from the group consisting of halogen, alkyl, alkoxy, haloalkyl, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl and heterocyclyl;
- R3 is selected from the group consisting of hydrogen atom, alkyl, alkoxy, halogen, haloalkyl, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclyl, aryl, heteroaryl, —C(O)R6, —C(O)OR6, —S(O)mR6, —NR7R8 and —C(O)NR7R8, wherein each of the cycloalkyl, heterocyclyl, aryl and heteroaryl is independently and optionally substituted by one or more substituents selected from the group consisting of alkyl, alkoxy, halogen, haloalkyl, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclyl, aryl, heteroaryl, —C(O)R6, —C(O)OR6, —S(O)mR6, —NR7R8 and —C(O)NR7R8;
- Ra and Rb are identical or different, and each is independently selected from the group consisting of hydrogen atom, halogen, alkyl, alkoxy, haloalkyl, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclyl, aryl and heteroaryl;
- R4 is selected from the group consisting of hydrogen atom, halogen, alkyl, alkoxy, haloalkyl, hydroxy, hydroxyalkyl, cyano, amino, nitro, cycloalkyl, heterocyclyl, aryl and heteroaryl;
- R5 is selected from the group consisting of hydrogen atom, alkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
- R6 is selected from the group consisting of hydrogen atom, alkyl, haloalkyl, amino, hydroxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
- R7 and R8 are identical or different, and each is independently selected from the group consisting of hydrogen atom, alkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein each of the alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl is independently and optionally substituted by one or more substituents selected from the group consisting of alkyl, alkoxy, halogen, amino, cyano, nitro, hydroxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
- or, R7 and R8 are linked together with the attached nitrogen atom to form heterocyclyl, wherein, except the one nitrogen atom, the heterocyclyl contains one or two identical or different heteroatoms selected from the group consisting of N, O and S, and the heterocyclyl is optionally substituted by one or more substituents selected from the group consisting of alkyl, alkoxy, halogen, amino, cyano, nitro, hydroxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
- n is 0, 1, 2, 3 or 4;
- and
- m is 0, 1 or 2.
16 more elements
Dependencies are inferred from the claim text.