US 2024/0391925 A1 · P2X3 AND/OR P2X2/3 COMPOUNDS AND METHODS

Abstract

The present disclosure provides novel compounds and methods for preparing and using these compounds. In one embodiment, the compounds are of the structure of formula (I), wherein R1-R7 are defined herein. In a further embodiment, these compounds are useful in method for regulating one or both of the P2X3 or P2X2/3 receptors. In another embodiment, these compounds are useful for treating pain in patients by administering one or more of the compounds to a patient. In another embodiment, these compounds are useful for treating respiratory dysfunction in patients by administering one or more of the compounds to a patient.

Claims20

Dependent claims

A compound of the structure of formula (I):

and prodrugs, enantiomers or pharmaceutically acceptable salts thereof, wherein:
R1 is H, halogen, C1-C6 alkyl, C3-C6 cycloalkyl, CN or CONH2;
R2 is none, C1-C6 alkyl or aryl;
R3 is none, optionally substituted C1-C6 alkyl, C3-C6 cycloalkyl or heterocycle;
R4 is optionally substituted heteroaryl, optionally substituted C1-C6 alkyl, optionally substituted C3-C6 cycloalkyl or optionally substituted aryl;
R5, R6 are independently H, C1-C6 alkyl or C3-C6 cycloalkyl;
and
R7 is CONHR8, optionally substituted heterocycle or optionally substituted heteroaryl, wherein R8 is H, alkyl or cycloalkyl.

5 more elements

A compound selected from the group consisting of:

1-{4-[2-Isopropyl-7-((R)-1-quinolin-3-yl-ethylamino)-2H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-{4-[2-Isopropyl-7-(1-quinolin-3-yl-ethylamino)-2H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-(4-{7-[2-(4-Chloro-phenyl)-1,1-dimethyl-ethylamino]-2-isopropyl-2H-pyrazolo[4,3-d]pyrimidin-5-yl}-piperazin-1-yl)-ethanone;
1-{4-[2-sec-Butyl-7-(1-quinolin-3-yl-ethylamino)-2H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-{4-[2-sec-Butyl-7-((R)-1-quinolin-3-yl-ethylamino)-2H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-(4-{2-sec-Butyl-7-[2-(4-chloro-phenyl)-1,1-dimethyl-ethylamino]-2H-pyrazolo[4,3-d]pyrimidin-5-yl}-piperazin-1-yl)-ethanone;
1-{4-[2-Isobutyl-7-((R)-1-quinolin-3-yl-ethylamino)-2H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-{4-[2-(1-Ethyl-propyl)-7-((R)-1-quinolin-3-yl-ethylamino)-2H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-{4-[2-Phenyl-7-((R)-1-quinolin-3-yl-ethylamino)-2H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
4-{1-sec-Butyl-7-[((R)-cyclopropyl-quinolin-3-yl-methyl)-amino]-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-piperazine-1-carboxylic acid amide;
1-{4-[1-Isopropyl-4-(1-quinolin-3-yl-ethylamino)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]-piperazin-1-yl}-ethanone;
1-{4-[1-Isopropyl-7-((R)-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-(4-{7-[2-(4-Chloro-phenyl)-1,1-dimethyl-ethylamino]-1-isopropyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-piperazin-1-yl)-ethanone;
1-(4-{1-Isopropyl-7-[(quinolin-3-ylmethyl)-amino]-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-piperazin-1-yl)-ethanone;
4-[1-Isopropyl-7-((R)-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-1-methyl-piperazin-2-one;
1-{4-[1-Isobutyl-7-((R)-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-{4-[1-Isopropyl-7-((S)-1-quinolin-3-yl-ethylamino)-2H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-{4-[1-sec-Butyl-7-((S)-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-{4-[1-((S)-sec-Butyl)-7-((R)-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
4-[1-sec-Butyl-7-((R)-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-1-methyl-piperazin-2-one;
1-{4-[1-((R)-sec-Butyl)-7-((R)-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-{4-[1-(1-Ethyl-propyl)-7-((R)-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-Ethyl-4-[1-isopropyl-7-((R)-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-2-one;
1-{4-[1-(2-Methoxy-1-methyl-ethyl)-7-((R)-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-{4-[1-Cyclopentyl-7-((R)-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-{4-[7-((R)-1-Quinolin-3-yl-ethylamino)-1-(tetrahydro-pyran-4-ylmethyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-{4-[7-((R)-1-Quinolin-3-yl-ethylamino)-1-(tetrahydro-pyran-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-{4-[1-Hexyl-7-((R)-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-{4-[7-{[1-(4-Chloro-phenyl)-cyclobutylmethyl]-amino}-1-(1-ethyl-propyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-{4-[7-[1-(4-Ethoxy-phenyl)-ethylamino]-1-(1-ethyl-propyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-[4-(1-sec-Butyl-7-{[1-(4-chloro-phenyl)-cyclobutylmethyl]-amino}-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-piperazin-1-yl]-ethanone;
1-{4-[1-Cyclobutylmethyl-7-((R)-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-{4-[7-[(S)-1-(4-Ethoxy-phenyl)-ethylamino]-1-(1-ethyl-propyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-{4-[1-Dicyclopropylmethyl-7-((R)-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-{4-[1-(1-Ethyl-propyl)-7-((R)-1-quinolin-3-yl-propylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-{4-[1-(1-Ethyl-propyl)-7-((S)-1-quinolin-3-yl-propylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-{4-[1-Isopropyl-7-((R)-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-propan-1-one;
1-{4-[1-sec-Butyl-7-((R)-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-propan-1-one;
1-{4-[7-(1-Benzofuran-5-yl-ethylamino)-1-(1-ethyl-propyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-{4-[1-(1-Ethyl-propyl)-7-((R)-1-naphthalen-2-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
4-[1-Isopropyl-7-((R)-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-2-one;
1-(4-{1-(1-Ethyl-propyl)-7-[1-(6-fluoro-quinolin-3-yl)-ethylamino]-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-piperazin-1-yl)-ethanone;
1-{4-[1-sec-Butyl-7-((R)-1-quinolin-3-yl-propylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-{4-[7-[((R)-Cyclopropyl-quinolin-3-yl-methyl)-amino]-1-(1-ethyl-propyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-(4-{1-sec-Butyl-7-[1-(2-methyl-benzofuran-5-yl)-ethylamino]-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-piperazin4.6-1-yl)-ethanone;
1-(4-{1-(1-Ethyl-propyl)-7-[1-(2-methyl-benzofuran-5-yl)-ethylamino]-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-piperazin-1-yl)-ethanone;
1-(4-{1-(1-Ethyl-propyl)-7-[1-(4-isopropoxy-phenyl)-ethylamino]-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-piperazin-1-yl)-ethanone;
1-{4-[1-Cyclobutyl-7-((R)-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
4-[1-Cyclobutyl-7-((R)-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-1-methyl-piperazin-2-one;
1-{4-[1-Ethyl-7-((R)-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
4-[1-(1-Ethyl-propyl)-7-((R)-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazine-1-carboxylic acid amide;
1-(4-{1-sec-Butyl-7-[1-(6-phenyl-pyridin-3-yl)-ethylamino]-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-piperazin-1-yl)-ethanone;
1-(4-{1-sec-Butyl-7-[1-(4-pyridin-2-yl-phenyl)-ethylamino]-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-piperazin-1-yl)-ethanone;
1-(4-{1-(1-Ethyl-propyl)-7-[(R)-1-(6-fluoro-quinolin-3-yl)-ethylamino]-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-piperazin-1-yl)-ethanone;
1-{4-[7-[1-(2-Cyclopropyl-benzofuran-5-yl)-ethylamino]-1-(1-ethyl-propyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-(4-{1-sec-Butyl-7-[((R)-cyclopropyl-quinolin-3-yl-methyl)-amino]-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-piperazin-1-yl)-ethanone;
1-{4-[7-(1-Benzo[b]thiophen-5-yl-ethylamino)-1-(1-ethyl-propyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-[4-(1-sec-Butyl-7-{[cyclopropyl-(6-phenyl-pyridin-3-yl)-methyl]-amino}-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-piperazin-1-yl]-ethanone;
4-{7-[((R)-Cyclopropyl-quinolin-3-yl-methyl)-amino]-1-isopropyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-1-methyl-piperazin-2-one;
1-{4-[1-(1,2-Dimethyl-propyl)-7-((R)-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-(4-{1-(1-Ethyl-propyl)-7-[(R)-1-(6-fluoro-quinolin-3-yl)-ethylamino]-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-piperazin-1-yl)-ethanone 1-{4-[7-[((R)-Cyclopropyl-quinolin-3-yl-methyl)-amino]-1-(1,2-dimethyl-propyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-{4-[7-{[Cyclopropyl-(6-cyclopropylmethoxy-pyridin-3-yl)-methyl]-amino}-1-(1-ethyl-propyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
4-{1-(1-Ethyl-propyl)-7-[(quinolin-3-ylmethyl)-amino]-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-piperazine-1-carboxylic acid amide;
1-{4-[7-{[Cyclopropyl-(6-fluoro-quinolin-3-yl)-methyl]-amino}-1-(1-ethyl-propyl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
4-{7-[((R)-Cyclopropyl-quinolin-3-yl-methyl)-amino]-1-isopropyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-piperazine-1-carboxylic acid amide;
4-{1-((S)-sec-Butyl)-7-[(cyclopropyl-imidazo[1,2-a]pyridin-6-yl-methyl)-amino]-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-piperazine-1-carboxylic acid amide;
4-{1-((S)-sec-Butyl)-7-[1-(6,7-difluoro-quinolin-3-yl)-ethylamino]-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-piperazine-1-carboxylic acid amide;
4-{1-((S)-sec-Butyl)-7-[((R)-cyclopropyl-quinolin-3-yl-methyl)-amino]-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-piperazine-1-carboxylic acid amide;
4-{1-((R)-sec-Butyl)-7-[((R)-cyclopropyl-quinolin-3-yl-methyl)-amino]-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-piperazine-1-carboxylic acid amide;
4-{1-((S)-sec-Butyl)-7-[1-(1H-indazol-3-yl)-ethylamino]-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-piperazine-1-carboxylic acid amide;
4-[7-[((R)-Cyclopropyl-quinolin-3-yl-methyl)-amino]-1-(tetrahydro-pyran-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazine-1-carboxylic acid amide;
4-[1-((S)-sec-Butyl)-7-(1-pyrazolo[1,5-a]pyridin-2-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazine-1-carboxylic acid amide;
((R)-Cyclopropyl-quinolin-3-yl-methyl)-[1-(1-ethyl-propyl)-5-[1,2,3]triazol-1-yl-1H-pyrazolo[4,3-d]pyrimidin-7-yl]-amine;
1-{1-sec-Butyl-7-[((R)-cyclopropyl-quinolin-3-yl-methyl)-amino]-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-piperidine-4-carboxylic acid amide;
4-{1-sec-Butyl-7-[((R)-cyclopropyl-quinolin-3-yl-methyl)-amino]-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-morpholine-2-carbonitrile;
1-{4-[1-sec-Butyl-3-methyl-7-((R)-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
(1-sec-Butyl-5-[1,2,4]triazol-1-yl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-((R)-cyclopropyl-quinolin-3-yl-methyl)-amine;
(1-sec-Butyl-5-tetrazol-1-yl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-((R)-cyclopropyl-quinolin-3-yl-methyl)-amine;
(1-sec-Butyl-5-tetrazol-2-yl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-((R)-cyclopropyl-quinolin-3-yl-methyl)-amine;
4-(1-((S)-sec-Butyl)-7-{[cyclopropyl-(1-ethyl-1H-indazol-5-yl)-methyl]-amino}-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-piperazine-1-carboxylic acidamide;
1-{4-[1-((S)-sec-Butyl)-7-(2-hydroxy-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-{4-[1-((S)-sec-Butyl)-7-(2-methoxy-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
4-{1-((S)-sec-Butyl)-7-[(cyclopropyl-quinoxalin-2-yl-methyl)-amino]-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-piperazine-1-carboxylic acid amide;
4-{1-sec-Butyl-7-[(R)-1-(7-methyl-imidazo[1,2-a]pyridin-2-yl)-ethylamino]-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-piperazine-1-carboxylic acid amide;
4-[1-sec-Butyl-7-((R)-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazine-1-carboxylic acid amide;
4-{1-(1-Cyclopropyl-ethyl)-7-[((R)-cyclopropyl-quinolin-3-yl-methyl)-amino]-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-piperazine-1-carboxylic acid amide;
1-sec-Butyl-7-[((R)-cyclopropyl-quinolin-3-yl-methyl)-amino]-1H-pyrazolo[4,3-d]pyrimidine-5-carboxylic acid amide;
1-{4-[1-sec-Butyl-7-((R)-1-quinolin-3-yl-ethylamino)-2H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-{4-[3-Bromo-1-sec-butyl-7-((R)-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
5-(4-Acetyl-piperazin-1-yl)-1-sec-butyl-7-((R)-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidine-3-carbonitrile;
1-{4-[1-sec-Butyl-3-cyclopropyl-7-((R)-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-{4-[3-Bromo-2-isopropyl-7-(1-quinolin-3-yl-ethylamino)-2H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
5-(4-Acetyl-piperazin-1-yl)-2-isopropyl-7-(1-quinolin-3-yl-ethylamino)-2H-pyrazolo[4,3-d]pyrimidine-3-carboxylic acid amide;
1-{4-[2-Isopropyl-3-methyl-7-(1-quinolin-3-yl-ethylamino)-2H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-(4-{3-Bromo-7-[2-(4-chloro-phenyl)-1,1-dimethyl-ethylamino]-2-isopropyl-2H-pyrazolo[4,3-d]pyrimidin-5-yl}-piperazin-1-yl)-ethanone;
1-{4-[3-Bromo-2-isopropyl-7-((R)-1-quinolin-3-yl-ethylamino)-2H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-{4-[3-Chloro-2-isopropyl-7-((R)-1-quinolin-3-yl-ethylamino)-2H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-{4-[3-Bromo-1-isopropyl-7-((R)-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
1-(4-{7-[2-(4-Chloro-phenyl)-1,1-dimethyl-ethylamino]-2-isopropyl-3-methyl-2H-pyrazolo[4,3-d]pyrimidin-5-yl}-piperazin-1-yl)-ethanone;
1-{4-[2-Isopropyl-3-methyl-7-((R)-1-quinolin-3-yl-ethylamino)-2H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
5-(4-Acetyl-piperazin-1-yl)-2-isopropyl-7-((R)-1-quinolin-3-yl-ethylamino)-2H-pyrazolo[4,3-d]pyrimidine-3-carbonitrile;
5-(4-Acetyl-piperazin-1-yl)-1-isopropyl-7-((R)-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidine-3-carbonitrile;
1-{4-[3-Bromo-2-sec-butyl-7-((R)-1-quinolin-3-yl-ethylamino)-2H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
5-(4-Acetyl-piperazin-1-yl)-2-sec-butyl-7-((R)-1-quinolin-3-yl-ethylamino)-2H-pyrazolo[4,3-d]pyrimidine-3-carbonitrile;
1-{4-[3-Cyclopropyl-2-isopropyl-7-((R)-1-quinolin-3-yl-ethylamino)-2H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazin-1-yl}-ethanone;
4-{1-sec-Butyl-7-[((R)-cyclopropyl-quinolin-3-yl-methyl)-amino]-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-piperaz4.53ine-1-sulfonic acid amide;
2-(4-{1-sec-Butyl-7-[((R)-cyclopropyl-quinolin-3-yl-methyl)-amino]-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-piperazin-1-yl)-acetamide;
4-{1-sec-Butyl-7-[((R)-cyclopropyl-quinolin-3-yl-methyl)-amino]-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-N′-cyanopiperazine-1-carboximidamide;
4-(1-sec-butyl-7-{[(R)-methyl(quinolin-3-yl)methyl]amino}-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-N′-cyanopiperazine-1-carboximidamide;
4-{1-sec-Butyl-7-[((R)-cyclopropyl-quinolin-3-yl-methyl)-amino]-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-piperazine-1-carboxamidine;
2-{4-[1-sec-Butyl-7-((R)-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-pyrazol-1-yl}-ethanol;
[1-sec-Butyl-5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl]-((R)-cyclopropyl-quinolin-3-yl-methyl)-amine;
[1-sec-Butyl-5-(1-ethyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl]-((R)-cyclopropyl-quinolin-3-yl-methyl)-amine;
{1-sec-Butyl-5-[1-(2-fluoro-ethyl)-1H-pyrazol-4-yl]-1H-pyrazolo[4,3-d]pyrimidin-7-yl}-((R)-cyclopropyl-quinolin-3-yl-methyl)-amine;
(R)-Cyclopropyl-quinolin-3-yl-methyl)-[5-(1-methyl-1H-pyrazol-4-yl)-1-(tetrahydro-pyran-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl]-amine;
4-{1-sec-Butyl-7-[((R)-cyclopropyl-quinolin-3-yl-methyl)-amino]-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-piperidine-1-carboxylic acid amide;
[1-sec-Butyl-5-(1H-pyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl]-((R)-cyclopropyl-quinolin-3-yl-methyl)-amine;
2-(4-{1-sec-Butyl-7-[((R)-cyclopropyl-quinolin-3-yl-methyl)-amino]-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-pyrazol-1-yl)-acetamide;
2-(4-{1-sec-Butyl-7-[((R)-cyclopropyl-quinolin-3-yl-methyl)-amino]-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-pyrazol-1-yl)-ethanol;
2-{1-((S)-sec-Butyl)-5-[1-(2-fluoro-ethyl)-1H-pyrazol-4-yl]-1H-pyrazolo[4,3-d]pyrimidin-7-ylamino}-2-quinolin-3-yl-ethanol;
{1-sec-Butyl-5-[1-(2-fluoro-ethyl)-1H-pyrazol-4-yl]-1H-pyrazolo[4,3-d]pyrimidin-7-yl}-[(R)-1-(7-methyl-imidazo[1,2-a]pyridin-2-yl)-ethyl]-amine;
4-[1-((S)-sec-Butyl)-7-(2-hydroxy-1-quinolin-3-yl-ethylamino)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-piperazine-1-carboxylic acid amide;
1-sec-Butyl-7-[((R)-cyclopropyl-quinolin-3-yl-methyl)-amino]-1H-pyrazolo[4,3-d]pyrimidine-5-carboxylic acid cyclopropylamide;
[1-sec-Butyl-5-(5-methyl-[1,3,4]oxadiazol-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-yl]-((R)-cyclopropyl-quinolin-3-yl-methyl)-amine;
1-{1-sec-Butyl-7-[((R)-cyclopropyl-quinolin-3-yl-methyl)-amino]-1H-pyrazolo[4,3-d]pyrimidin-5-yl}-1H-[1,2,3]triazole-4-carboxylic acid amide;
and
(1-sec-Butyl-5-pyridazin-3-yl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-((R)-cyclopropyl-quinolin-3-yl-methyl)-amine.

124 more elements

Dependencies are inferred from the claim text.

Facts

Application

18/795,061Filed 5 Aug 2024

Priority

30 Sep 2016

Published

28 Nov 2024

Term ends

Not estimatedThe source records don’t support an estimate.

Classification11 codes

C07D 487/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61P 11/00
Drugs for disorders of the respiratory system
A61P 11/06
Drugs for disorders of the respiratory system: antiasthmatics
A61P 11/08
Drugs for disorders of the respiratory system: bronchodilators

Family

Application62/402,280Us provisional application · filed 30 Sep 2016

Application15/717,185Continuation · filed 27 Sep 2017

Application16/205,553Continuation · filed 30 Nov 2018

Application16/800,278Continuation · filed 25 Feb 2020

Application17/706,690Continuation · filed 29 Mar 2022

Application18/795,061Continuation

US 10,174,039 B2Related patent

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US 2018/0093991 A1Published application

US 2019/0092778 A1Published application

US 2020/0190096 A1Published application

US 2022/0227774 A1Published application

US 2024/0391925 A1This patent

From the US filing history. Foreign family members aren’t listed.