# US 12,760,026 B2 · Heteroaroyl amides as LRRK2 inhibitors, pharmaceutical compositions, and uses thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,760,026 B2 - Document ID: US12760026B2 - Status: Granted - Kind: B2 - Application number: 18/549,223 - Filed: 2022-03-14 - Published: 2024-05-30 - Granted: 2026-10-13 - Earliest claimed: 2021-03-17 - Assignees: Merck Sharp & Dohme Corp. - Applicants: Merck Sharp & Dohme LLC - Inventors: Kaleen Konrad Childers; J. Michael Ellis; Peter J. Fuller; Hakan Gunaydin; Jack D. Scott; Haiqun Tang; Charles S. Yeung - Web page: https://patentgrep.com/patent/US12760026B2 ## CPC - C07D 487/04: Ortho-condensed systems - A61K 31/4155: non condensed and containing further heterocyclic rings - A61K 31/422: not condensed and containing further heterocyclic rings - A61K 31/427: not condensed and containing further heterocyclic rings - A61K 31/437: the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline - A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) - A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin - A61K 31/506: not condensed and containing further heterocyclic rings - A61K 31/5365: ortho- or peri-condensed with heterocyclic ring systems - A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol - A61K 31/55: having seven-membered rings, e.g. azelastine, pentylenetetrazole - C07D 401/12: linked by a chain containing hetero atoms as chain links - C07D 401/14: containing three or more hetero rings - C07D 403/12: linked by a chain containing hetero atoms as chain links - C07D 403/14: containing three or more hetero rings - C07D 413/12: linked by a chain containing hetero atoms as chain links - C07D 413/14: containing three or more hetero rings - C07D 417/12: linked by a chain containing hetero atoms as chain links - C07D 417/14: containing three or more hetero rings - C07D 471/04: Ortho-condensed systems - C07D 498/04: Ortho-condensed systems - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## Abstract The present invention is directed to certain (hetero)aroyl 4-aminopyrazole derivatives of Formula (I) and pharmaceutically acceptable salts thereof, wherein A, R1, R2, and R3 are as defined herein, which are potent inhibitors of LRRK2 kinase and may be useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease and other diseases and disorders described herein. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which LRRK-2 kinase is involved. ## Claims ### Claim 1 A compound having a structural Formula (I): or a pharmaceutically acceptable salt thereof, wherein: A is a heteroaryl or aryl selected from the group consisting of thiazolyl, pyrazolyl, pyridyl, phenyl, pyrimidinyl, oxazolyl and pyrazinyl; R1 is selected from hydrogen, C1-6 alkyl, —(CH2)nOC1-6 alkyl, —(CH2) halogen, —(CH2)nCN, C1-6 haloalkyl, —CH(R)2, —(CH2)nC3-6cycloalkyl, —(CH2)nC6-10aryl, —(CH2)nC5-10heteroaryl, —(CH2)nC4-10heterocyclyl, and —(CH2)nN(R)2, said alkyl and cycloalkyl, aryl, heteroaryl, and heterocyclyl optionally substituted with 1 to 3 groups selected from Rx; R is selected from hydrogen, C1-6 alkyl, cyclopropyl, CN, NHCH(CH3)2, and phenyl, said phenyl optionally substituted with 1 to 3 groups of Rx; R2 is selected from hydrogen, C1-6 alkyl, —OC1-6 alkyl, halogen, C(O) C1-6alkyl, C(O)N(R)2, —C(O) OC1-6alkyl, CN, C1-6haloalkyl, —C3-6cycloalkyl, (O)0-1C6-10aryl, C5-10heteroaryl, and —(CH2)nN(R)2, said alkyl and cycloalkyl, aryl, and heteroaryl optionally substituted with 1 to 3 groups selected from Rx; Ra is selected from C1-6 alkyl, CN and halogen; Rb are independently selected from C1-6 alkyl, —OC1-6 alkyl, C3-6 cycloalkyl, —SC1-6alkyl, C6-10aryl, C5-10heteroaryl, C3-10heterocyclyl, NHC(O)C1-6alkyl, N(R)2, and —NHC6-10aryl, said alkyl, aryl, heteroaryl, and heterocyclyl optionally substituted with 1 to 3 groups of Ry; Rx is selected from C1-6 alkyl, —OC1-6 alkyl, OH, C3-6 cycloalkyl —CH2SC1-6 alkyl, —OCH2OC1-6 alkyl, halogen, —SO2CH3, CN, and (CH2)nN(R)2, Ry is selected from hydrogen, C1-6 alkyl, —(CH2)nOC1-6 alkyl, C3-6cycloalkyl, C1-6 haloalkyl, -halogen, CN, (CH2)nC4-10heterocyclyl, —(CH2)n 5-10heteroaryl, and —SO2C1-6 alkyl; and n is selected from 0 to 3 with the provisio that when A is phenyl, thiazolyl and oxazolyl then R2 is not benzimidazolyl or pyridyl; when A is pyrimidinyl or pyrazinyl it is not substituted with NH2; and when A is pyridyl then R1 is not CH2CF3. ### Claim 2 (depends on 1) The compound according to claim 1 or a pharmaceutically acceptable salt thereof wherein A is thiazolyl. ### Claim 3 (depends on 1) The compound according to claim 1 or a pharmaceutically acceptable salt thereof wherein A is pyridyl. ### Claim 4 (depends on 1) The compound according to claim 1 or a pharmaceutically acceptable salt thereof wherein A is phenyl. ### Claim 5 (depends on 1) The compound according to claim 1 or a pharmaceutically acceptable salt thereof wherein A is oxazolyl. ### Claim 6 (depends on 1) The compound according to claim 1 or a pharmaceutically acceptable salt thereof wherein R1 is selected from the group consisting of —(CH2)ncyclobutyl, —(CH2)ncyclopropyl, CH(cyclopropyl)2, —(CH2)ncyclopentyl, —(CH2)ncyclohexyl, CH3, CH(CH3)2, CH2 CH(CH3)2, CH2CH3, C(CH3)3, (CH2)nCN, CH(CH3) CN, CH2CF3, CHF2, CH2OH, CH2CHF2, (CH2)nOCH3, (CH2)nF, (CH2)nphenyl, (CH2)nnapthyl, (CH2)npyridyl, (CH2)npyrrolyl, tetrahydrotriazoloazepinyl, (CH2)noxetanyl, (CH2)npiperidinyl, (CH2)ntetrahydropyranyl, (CH2)ntetrahydrofuranyl, (CH2)npiperazinyl, (CH2)npyrrolidinyl, (CH2)nimidazolyl, (CH2)ntriazoloazepinyl, (CH2)ntetrahydrotriazolyl, (CH2) morpholinyl, and (CH2)nazabicyclooctanyl said cyclobutyl cyclopropyl, cyclopentyl, cyclohexyl, phenyl, napthyl, pyridyl, pyrrolyl, tetrahydrotriazoloazepinyl, oxetanyl, piperidinyl, tetrahydropyranyl, tetrahydrofuranyl, piperazinyl, pyrrolyl, imidazolyl, triazoloazepinyl, tetrahydrotriazolyl, morpholinyl and azabicylooctanyl unsubstituted or substituted with 1 to 3 groups of Rx. ### Claim 7 (depends on 1) The compound according to claim 1 or a pharmaceutically acceptable salt thereof wherein R1 is selected from the group consisting of —(CH2)ncyclobutyl, —(CH2)ncyclopropyl, CH3, CH(CH3)2, CH2CH3, C(CH3)3, CH2CF3, CHF2, CH2CHF2, (CH2)nOCH3, and (CH2)nF. ### Claim 8 (depends on 1) The compound according to claim 1 or a pharmaceutically acceptable salt thereof wherein R2 is selected from the group consisting of hydrogen, CH3, OCH2CF3, OCH3, CHF2, OCH(CH3)2, OCH2CHF2, C(O)OCH3, CF3, CN, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, —Ophenyl, said phenyl, —Ophenyl, pyridyl, tetrahydrotriazopyridyl, or pyrazolyl unsubstituted or substituted with 1 to 3 groups from Rx. ### Claim 9 The compound according to 1 or a pharmaceutically acceptable salt there of wherein R2 is selected from the group consisting of hydrogen, CH3, and CHF2. ### Claim 10 (depends on 1) The compound according to claim 1 or a pharmaceutically acceptable salt thereof where Rb is selected from the group consisting of C1-6alkyl, cyclopropyl and cyclobutyl, —SC1-6alkyl, phenyl, —NHphenyl, pyridyl, pyrimidinyl, pyrazolyl, furanyl, imidazolyl, thiazolyl, isothiazolyl, pyrrolyl, oxazinylthiazolyl, pyridazinyl, and benzothiophenyl, said alkyl, cyclopropyl, cyclobutyl, phenyl, pyridyl, pyrimidinyl, pyrazolyl, furanyl, imidazolyl, thiazolyl, isothiazolyl, pyrrolyl, and benzothiophenyl unsubstituted or substituted with 1 to 3 groups of Ry. ### Claim 11 (depends on 1) The compound according to claim 1 or a pharmaceutically acceptable salt thereof wherein Rb is pyrazolyl unsubstituted or substituted with 1 to 3 groups of Ry. ### Claim 12 (depends on 1) The compound according to claim 1 or a pharmaceutically acceptable salt thereof wherein Rb is pyridyl unsubstituted or substituted with 1 to 3 groups of Ry. ### Claim 13 (depends on 1) The compound according to claim 1 or a pharmaceutically acceptable salt thereof represented by Formula II: or a pharmaceutically acceptable salt thereof, wherein X is S or O, and R3 is selected from the group consisting of hydrogen, C1-6 alkyl, (CH2)nOC1-6 alkyl, C1-6 haloalkyl, (CH2)nC5-10heteroaryl, halogen, CN, and SO2C1-6 alkyl, said alkyl and aryl unsubstituted or substituted with 1 to 3 groups from Rx. ### Claim 14 (depends on 13) The compound according to claim 13 or a pharmaceutically acceptable salt thereof wherein X is S, R1 is selected from CH3, CH2CH3, CH(CH3)2, —(CH2)ncyclopropyl, —(CH2)ncyclobutyl, and CH(cyclopropyl)2, and R2 is selected from hydrogen, CH3, OCH2CF3, OCH3, CHF2, OCH(CH3)2, OCH2CHF2, CF3, C(O) OCH3, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, —O-phenyl, pyridyl, tetrahydrotriazopyridyl, pyrazolyl, and CN, said cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, —O-phenyl, pyridyl, tetrahydrotriazopyridyl, pyrazolyl unsubstituted or substituted with 1 to 3 groups of Rx. ### Claim 15 (depends on 1) The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein said compound is selected from: N-(1-Cyclobutyl-1H-pyrazol-4-yl)-2-(1H-pyrazol-4-yl)thiazole-4-carboxamide, N-(3-Methoxy-1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-2-(1H-pyrazol-4-yl)thiazole-4- carboxamide, N-(1-Cyclobutyl-3-methyl-1H-pyrazol-4-yl)-2-(1H-pyrazol-4-yl)thiazole-4-carboxamide, N-[1-methyl-3-(methylcarbamoyl)-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-[1-(difluoromethyl)-3-methyl-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-(1,3-dicyclopropyl-1H-pyrazol-4-yl)-2-(1H-pyrazol-4-yl)-1,3-thiazole-4-carboxamide N-[1-(1-methylethyl)-3-(2,2,2-trifluoroethoxy)-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3- thiazole-4-carboxamide 2-(1H-pyrazol-4-yl)-N-(1-pyridin-4-yl-1H-pyrazol-4-yl)-1,3-thiazole-4-carboxamide N-(1-methyl-3-pyridin-4-yl-1H-pyrazol-4-yl)-2-(1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-(3-cyano-1-ethyl-1H-pyrazol-4-yl)-2-(1H-pyrazol-4-yl)-1,3-thiazole-4-carboxamide N-[3-(4-fluorophenyl)-1-methyl-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-[1-ethyl-3-(5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3-yl)-1H-pyrazol-4-yl]-2- (1H-pyrazol-4-yl)-1,3-thiazole-4-carboxamide N-(3-carbamoyl-1-methyl-1H-pyrazol-4-yl)-2-(1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-(3-methoxy-1-methyl-1H-pyrazol-4-yl)-2-(1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-[3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-[1-methyl-3-(1-methylethoxy)-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-(1-tert-butyl-1H-pyrazol-4-yl)-2-(1H-pyrazol-4-yl)-1,3-thiazole-4-carboxamide N-(1-cyclopropyl-1H-pyrazol-4-yl)-2-(1H-pyrazol-4-yl)-1,3-oxazole-4-carboxamide methyl 1-methyl-4-({[2-(1H-pyrazol-4-yl)-1,3-thiazol-4-yl]carbonyl}amino)-1H-pyrazole- 3-carboxylate N-[1-(1-methylethyl)-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3-thiazole-4-carboxamide 2-(1H-pyrazol-4-yl)-N-(1-pyridin-4-yl-1H-pyrazol-4-yl)-1,3-oxazole-4-carboxamide N-(1-cyclobutyl-3-methoxy-1H-pyrazol-4-yl)-2-(1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-[1-(dicyclopropylmethyl)-3-methyl-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3-thiazole- 4-carboxamide N-(1-phenyl-1H-pyrazol-4-yl)-2-(1H-pyrazol-4-yl)-1,3-thiazole-4-carboxamide N-(1-cyclopropyl-1H-pyrazol-4-yl)-2-(1H-pyrazol-4-yl)-1,3-thiazole-4-carboxamide N-[3-(2,2-difluoroethoxy)-1-methyl-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-[1-({1-[(methylsulfanyl)methyl]cyclobutyl}methyl)-1H-pyrazol-4-yl]-2-(1H-pyrazol-4- yl)-1,3-thiazole-4-carboxamide N-[3-methoxy-1-(6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepin-3-ylmethyl)-1H- pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3-thiazole-4-carboxamide N-(1-{[1-(methoxymethyl)cyclobutyl]methyl}-1H-pyrazol-4-yl)-2-(1H-pyrazol-4-yl)-1,3- thiazole-4-carboxamide N-(1-methyl-3-phenoxy-1H-pyrazol-4-yl)-2-(1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-(1,1′-dimethyl-1H,1′H-3,4′-bipyrazol-4-yl)-2-(1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-{1-[(3,3-dimethylcyclobutyl)methyl]-1H-pyrazol-4-yl}-2-(1H-pyrazol-4-yl)-1,3- thiazole-4-carboxamide N-(1-cyclobutyl-1H-pyrazol-4-yl)-2-(1H-pyrazol-4-yl)-1,3-oxazole-4-carboxamide N-{1-[(1-methylcyclobutyl)methyl]-1H-pyrazol-4-yl}-2-(1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-{1-[(3,3-difluorocyclobutyl)methyl]-1H-pyrazol-4-yl}-2-(1H-pyrazol-4-yl)-1,3- thiazole-4-carboxamide N-[3-(dimethylcarbamoyl)-1-methyl-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-(1-cyclopropyl-3-methoxy-1H-pyrazol-4-yl)-2-(1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-[1-cyclopropyl-3-(difluoromethyl)-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3-thiazole- 4-carboxamide N-[1-(1-methylethyl)-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3-oxazole-4-carboxamide N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-(1,3-dimethyl-1H-pyrazol-4-yl)-2-(1H-pyrazol-4-yl)-1,3-thiazole-4-carboxamide N-(3-cyclopropyl-1-methyl-1H-pyrazol-4-yl)-2-(1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-{1-[(1-fluorocyclobutyl)methyl]-1H-pyrazol-4-yl}-2-(1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-[1-({1-[(methylsulfonyl)methyl]cyclobutyl } methyl)-1H-pyrazol-4-yl]-2-(1H-pyrazol-4- yl)-1,3-thiazole-4-carboxamide N-[1-(4-fluorobenzyl)-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3-oxazole-4-carboxamide N-[3-(2,2-difluoroethoxy)-1-(1-methylethyl)-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3- thiazole-4-carboxamide (R)— or (S)—N-(1-(1-Cyclopropylethyl)-1H-pyrazol-4-yl)-2-(1H-pyrazol-4-yl)thiazole-4- carboxamide (R)— or (S)—N-{1-[1-cyclopropylethyl]-3-methyl-1H-pyrazol-4-yl}-2-(1H-pyrazol-4-yl)- 1,3-thiazole-4-carboxamide (S)— or (R)—N-{1-[1-cyclopropylethyl]-3-methyl-1H-pyrazol-4-yl}-2-(1H-pyrazol-4-yl)- 1,3-thiazole-4-carboxamide N-(1-(1-Cyclopropylethyl)-3-(difluoromethyl)-1H-pyrazol-4-yl)-2-(1H-pyrazol-4- yl)thiazole-4-carboxamide N-(1-cyclobutyl-3-cyclopropyl-1H-pyrazol-4-yl)-2-(1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-(1-cyclobutyl-5-cyclopropyl-1H-pyrazol-4-yl)-2-(1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide (R)— or (S)—N-(1-(1-Cyclopropylethyl)-5-(difluoromethyl)-1H-pyrazol-4-yl)-2-(1H- pyrazol-4-yl)thiazole-4-carboxamide N-(1-Cyclopropyl-1H-pyrazol-4-yl)-6-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4- yl)picolinamide 5-cyano-N-(1-cyclobutyl-1H-pyrazol-4-yl)-6-methylpyridine-2-carboxamide N-(1-cyclobutyl-1H-pyrazol-4-yl)-2-[(1-methylethyl)amino]-1,3-thiazole-4-carboxamide N-(1-cyclobutyl-1H-pyrazol-4-yl)-2-phenyl-1,3-oxazole-4-carboxamide N-(1-cyclobutyl-1H-pyrazol-4-yl)-2-(methylsulfanyl)-1,3-thiazole-4-carboxamide N-(1-cyclobutyl-1H-pyrazol-4-yl)-6-(1-methylethoxy)pyridine-2-carboxamide N-(1-cyclobutyl-1H-pyrazol-4-yl)-1-phenyl-1H-pyrazole-3-carboxamide 6-(acetylamino)-N-(1-cyclobutyl-1H-pyrazol-4-yl)pyridine-2-carboxamide N-(1-cyclobutyl-1H-pyrazol-4-yl)-2-phenyl-1,3-thiazole-4-carboxamide N-(1-cyclobutyl-1H-pyrazol-4-yl)-6-methoxypyridine-2-carboxamide N-(1-cyclobutyl-1H-pyrazol-4-yl)-1-pyrimidin-2-yl-1H-pyrazole-3-carboxamide 2-(acetylamino)-N-(1-cyclobutyl-1H-pyrazol-4-yl)-1,3-thiazole-4-carboxamide N-(1-cyclobutyl-1H-pyrazol-4-yl)-6-(1H-pyrazol-1-yl)pyridine-2-carboxamide N-(1-cyclobutyl-1H-pyrazol-4-yl)-2-(phenylamino)-1,3-thiazole-4-carboxamide N-(1-methyl-1H-pyrazol-4-yl)-2-(1H-pyrazol-4-yl)thiazole-4-carboxamide N-(1-cyclobutyl-1H-pyrazol-4-yl)-6-(pyrrolidin-1-yl)picolinamide N-(1-cyclobutyl-1H-pyrazol-4-yl)-6-(1H-imidazol-1-yl)picolinamide N-(1-cyclobutyl-1H-pyrazol-4-yl)-6-(piperidin-1-yl)picolinamide N-(1-((3-Fluorooxetan-3-yl)methyl)-1H-pyrazol-4-yl)-2-(1H-pyrazol-4-yl)thiazole-4- carboxamide N-(3-(Hydroxymethyl)-1-methyl-1H-pyrazol-4-yl)-2-(1H-pyrazol-4-yl)thiazole-4- carboxamide N-(1-(Cyclobutylmethyl)-1H-pyrazol-4-yl)-2-(1H-pyrazol-4-yl)thiazole-4-carboxamide N-[1-(2,2-difluoroethyl)-3-(difluoromethyl)-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3- thiazole-4-carboxamide N-[3-(difluoromethyl)-1-(2-methoxyethyl)-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3- thiazole-4-carboxamide N-{1-[(piperidin-4-yl)methyl]-1H-pyrazol-4-yl}-2-(1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-[3-(difluoromethyl)-1-(tetrahydro-2H-pyran-2-ylmethyl)-1H-pyrazol-4-yl]-2-(1H- pyrazol-4-yl)-1,3-thiazole-4-carboxamide N-{1-[3-(dimethylamino)propyl]-1H-pyrazol-4-yl}-2-(1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-[3-(difluoromethyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazol-4-yl]-2-(1H- pyrazol-4-yl)-1,3-thiazole-4-carboxamide N-{1-[(4,4-difluorocyclohexyl)methyl]-1H-pyrazol-4-yl}-2-(1H-pyrazol-4-yl)-1,3- thiazole-4-carboxamide N-[3-(difluoromethyl)-1-(2-fluoroethyl)-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3- thiazole-4-carboxamide 2-(1H-pyrazol-4-yl)-N-[1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl]-1,3-thiazole-4- carboxamide N-[1-(cyclobutylmethyl)-3-(difluoromethyl)-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3- thiazole-4-carboxamide N-[3-(difluoromethyl)-1-(tetrahydrofuran-2-ylmethyl)-1H-pyrazol-4-yl]-2-(1H-pyrazol-4- yl)-1,3-thiazole-4-carboxamide 2-(1H-pyrazol-4-yl)-N-[1-(tetrahydrofuran-2-ylmethyl)-1H-pyrazol-4-yl]-1,3-thiazole-4- carboxamide N-[1-(cyclopropylmethyl)-3-methoxy-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3-thiazole- 4-carboxamide N-{1-[2-(piperazin-1-yl)ethyl]-1H-pyrazol-4-yl}-2-(1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-[3-methoxy-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)- 1,3-thiazole-4-carboxamide N-[1-(4-fluorobenzyl)-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3-thiazole-4-carboxamide N-[3-(difluoromethyl)-1-(1-methylethyl)-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3- thiazole-4-carboxamide N-[1-(cyclobutylmethyl)-3-methoxy-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-[1-(2,2-difluoroethyl)-3-methoxy-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-[3-methoxy-1-(2-methoxyethyl)-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-[1-(2-methoxyethyl)-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3-thiazole-4-carboxamide N-[3-(difluoromethyl)-1-(2-methylpropyl)-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3- thiazole-4-carboxamide 2-(1H-pyrazol-4-yl)-N-[1-(pyridin-4-ylmethyl)-1H-pyrazol-4-yl]-1,3-thiazole-4- carboxamide N-{1-[(1-cyanocyclopropyl)methyl]-3-methoxy-1H-pyrazol-4-yl}-2-(1H-pyrazol-4-yl)- 1,3-thiazole-4-carboxamide 2-(1H-pyrazol-4-yl)-N-(1-{[(3S)-pyrrolidin-3-yl]methyl}-1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-[1-(cyanomethyl)-3-(difluoromethyl)-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3- thiazole-4-carboxamide N-{1-[(4-cyanopiperidin-4-yl)methyl]-1H-pyrazol-4-yl}-2-(1H-pyrazol-4-yl)-1,3-thiazole- 4-carboxamide N-{1-[(2,2-difluorocyclopropyl)methyl]-3-(difluoromethyl)-1H-pyrazol-4-yl}-2-(1H- pyrazol-4-yl)-1,3-thiazole-4-carboxamide 2-(1H-pyrazol-4-yl)-N-(1-{[(3R)-pyrrolidin-3-yl]methyl}-1H-pyrazol-4-yl)-1,3-thiazole- 4-carboxamide N-[1-(1-cyanoethyl)-3-(difluoromethyl)-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3- thiazole-4-carboxamide N-{1-[2-(piperidin-4-yl)ethyl]-1H-pyrazol-4-yl}-2-(1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-[1-(cyclopropylmethyl)-3-(difluoromethyl)-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3- thiazole-4-carboxamide N-{1-[3-(4-methylpiperazin-1-yl)propyl]-1H-pyrazol-4-yl}-2-(1H-pyrazol-4-yl)-1,3- thiazole-4-carboxamide N-{1-[(cis-4-amino-1-fluorocyclohexyl)methyl]-1H-pyrazol-4-yl}-2-(1H-pyrazol-4-yl)- 1,3-thiazole-4-carboxamide N-(1-{[4-(aminomethyl)-1-fluorocyclohexyl]methyl} -1H-pyrazol-4-yl)-2-(1H-pyrazol-4- yl)-1,3-thiazole-4-carboxamide N-{1-[(4-cyanocyclohexyl)methyl]-1H-pyrazol-4-yl}-2-(1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-[1-(cyclopropylmethyl)-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-{1-[(2,2-difluorocyclopropyl)methyl]-3-methoxy-1H-pyrazol-4-yl}-2-(1H-pyrazol-4- yl)-1,3-thiazole-4-carboxamide N-[3-(difluoromethyl)-1-(2-ethoxyethyl)-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3- thiazole-4-carboxamide N-[1-(2-methylpropyl)-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3-thiazole-4-carboxamide N-{3-(difluoromethyl)-1-[(3-methyloxetan-3-yl)methyl]-1H-pyrazol-4-yl}-2-(1H-pyrazol- 4-yl)-1,3-thiazole-4-carboxamide N-{1-[(3-azabicyclo[3.2.1]octan-8-yl)methyl]-1H-pyrazol-4-yl}-2-(1H-pyrazol-4-yl)-1,3- thiazole-4-carboxamide N-(1-(2-Methylpyridin-4-yl)-1H-pyrazol-4-yl)-2-(1H-pyrazol-4-yl)thiazole-4- carboxamide N-[1-(3-methylpyridin-4-yl)-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-{1-[2-(1-methylethyl)pyridin-4-yl]-1H-pyrazol-4-yl}-2-(1H-pyrazol-4-yl)-1,3-thiazole- 4-carboxamide N-[1-(2,6-dimethylpyridin-4-yl)-1H-pyrazol-4-yl]-2-(1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-(1-Cyclobutyl-1H-pyrazol-4-yl)-6-(1-methyl-1H-pyrazol-4-yl)picolinamide N-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-6-pyrimidin-5-ylpyridine-2-carboxamide N-(1-cyclobutyl-1H-pyrazol-4-yl)-2-(5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)-1,3- thiazole-4-carboxamide N-(1-cyclobutyl-1H-pyrazol-4-yl)-2-(1-ethyl-1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-6-furan-3-ylpyridine-2-carboxamide N-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-6-[1-(pyridin-4-ylmethyl)-1H-pyrazol-4- yl]pyridine-2-carboxamide N-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-6-(6-methyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazin-3-yl)pyridine-2-carboxamide N-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-6-[1-(pyridin-2-ylmethyl)-1H-pyrazol-4- yl]pyridine-2-carboxamide N-(1-cyclobutyl-1H-pyrazol-4-yl)-2-(1-methyl-1H-imidazol-4-yl)-1,3-thiazole-4- carboxamide N-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-6-(6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin- 3-yl)pyridine-2-carboxamide N-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-6-(2,4-difluorophenyl)pyridine-2-carboxamide N-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-6-[1-(2-methoxyethyl)-1H-pyrazol-4- yl]pyridine-2-carboxamide N-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-6-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3- yl)pyridine-2-carboxamide N-(1-cyclobutyl-1H-pyrazol-4-yl)-2-(1H-pyrazol-3-yl)-1,3-thiazole-4-carboxamide N-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-6-isothiazol-4-ylpyridine-2-carboxamide N-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-2,4′-bipyridine-6-carboxamide N-(1-cyclobutyl-1H-pyrazol-4-yl)-2-[1-(difluoromethyl)-1H-pyrazol-4-yl]-1,3-thiazole-4- carboxamide N-(1-cyclobutyl-1H-pyrazol-4-yl)-2-(5-methyl-1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-6-pyridazin-4-ylpyridine-2-carboxamide N-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-6-(1-methyl-1H-pyrazol-5-yl)pyridine-2- carboxamide N-(1-cyclobutyl-1H-pyrazol-4-yl)-2-(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)- 1,3-thiazole-4-carboxamide N-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-6-(1-methyl-1H-pyrazol-3-yl)pyridine-2- carboxamide N-(1-cyclobutyl-1H-pyrazol-4-yl)-2-(1-methyl-1H-pyrazol-4-yl)pyrimidine-4- carboxamide N-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-2′-fluoro-2,3′-bipyridine-6-carboxamide N-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-6-(1-methyl-1H-pyrazol-4-yl)pyridine-2- carboxamide N-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-6-(3,5-dimethyl-1H-pyrazol-4-yl)pyridine-2- carboxamide N-(1-cyclobutyl-1H-pyrazol-4-yl)-2-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)-1,3- thiazole-4-carboxamide N-(1-cyclobutyl-1H-pyrazol-4-yl)-2-(1-methyl-1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide 6-(3-cyanophenyl)-N-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]pyridine-2-carboxamide N-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-4′-methoxy-2,3′-bipyridine-6-carboxamide 6-(1-benzothiophen-3-yl)-N-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]pyridine-2- carboxamide N-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-6-(1-methyl-1H-pyrrol-3-yl)pyridine-2- carboxamide N-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-6-[1-(difluoromethyl)-1H-pyrazol-4- yl]pyridine-2-carboxamide N-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-2,3′-bipyridine-6-carboxamide N-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-6-[1-(2-morpholin-4-ylethyl)-1H-pyrazol-4- yl]pyridine-2-carboxamide N-[1-(cyclobutylmethyl)-1H-pyrazol-4-yl]-6-[1-(pyridin-3-ylmethyl)-1H-pyrazol-4- yl]pyridine-2-carboxamide N-(1-cyclobutyl-1H-pyrazol-4-yl)-6-(1-methyl-1H-pyrazol-4-yl)pyrazine-2-carboxamide N-(1-cyclobutyl-1H-pyrazol-4-yl)-2-fluoro-3-(1-methyl-1H-pyrazol-4-yl)benzamide N-(1-cyclobutyl-1H-pyrazol-4-yl)-2-(pyridin-3-yl)thiazole-4-carboxamide N-(1-cyclopropyl-1H-pyrazol-4-yl)-2-(1H-pyrazol-5-yl)thiazole-4-carboxamide 6-(1-Cyanocyclopropyl)-N-(1-(cyclobutylmethyl)-1H-pyrazol-4-yl)picolinamide N-(1-Cyclobutyl-1H-pyrazol-4-yl)-2-(1H-pyrazol-1-yl)thiazole-4-carboxamide N-(1-cyclobutyl-1H-pyrazol-4-yl)-2-(1H-imidazol-1-yl)thiazole-4-carboxamide N-(1-(Cyclobutylmethyl)-1H-pyrazol-4-yl)-2-(1-methyl-1H-pyrazol-4-yl)thiazole-4- carboxamide N-(1-cyclobutyl-3-cyclopropyl-1H-pyrazol-4-yl)-2-(1-methyl-1H-pyrazol-4-yl)-1,3- thiazole-4-carboxamide N-(1,3-dicyclopropyl-1H-pyrazol-4-yl)-2-(1-methyl-1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide 2-(1-ethyl-1H-pyrazol-4-yl)-N-[3-methoxy-1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]-1,3- thiazole-4-carboxamide N-(1-cyclobutyl-3-methyl-1H-pyrazol-4-yl)-2-(1-methyl-1H-pyrazol-4-yl)-1,3-thiazole-4- carboxamide N-[3-methoxy-1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl]-2-(1-methyl-1H-pyrazol-4-yl)- 1,3-thiazole-4-carboxamide N-(3-Methoxy-1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-2-(1-(methylsulfonyl)-1H- pyrazol-4-yl)thiazole-4-carboxamide ### Claim 16 (depends on 1) A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier. ### Claim 17 (depends on 1) A method of treating Parkinson's Disease comprising administering an effective amount of a compound of any of claim 1 or a pharmaceutically acceptable salt thereof, to a person in need thereof. ### Claim 18 (depends on 1) A method for the treatment or prophylaxis of an condition in which LRRK2 kinase is involved comprising administering to a subject in need thereof an effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof, said condition selected from: abnormal motor symptoms associated with Parkinson's disease, non-motor symptoms associated with Parkinson's disease, Lewy body dementia, L-Dopa induced dyskinesias, Alzheimer's disease, mild cognitive impairment, the transition from mild cognitive impairment to Alzheimer's disease, tauopathy disorders characterized by hyperphosphorylation of tau argyrophilic grain disease, Picks disease, corticobasal degeneration, progressive supranuclear palsy, inherited frontotemporal dementia, and Parkinson's disease linked to chromosome 17, neuroinflammation associated with of microglial inflammatory responses associated with multiple sclerosis, HIV-induced dementia, ALS, ischemic stroke, traumatic brain injury and spinal cord injury, lymphomas, leukemias, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, autoimmune hemolytic anemia, pure red cell aplasia, idiopathic thrombocytopenia pupura (ITP), Evans Syndrome, vasculitis, bullous skin disorder, type I diabetes mellitus, Sjorgen's syndrome, Delvic's disease, inflammatory myopathies, and ankylosing spondylitis, renal cancer, breast cancer, lung cancer, prostate cancer, and acute myelogenous leukemia (AML) in subjects expressing the LRRK2 G2019S mutation, papillary renal and thyroid carcinomas in a subject in whom LRRK2 is amplified or overexpressed, Crohn's disease and leprosy.