# US 12,006,325 B2 · Substituted furanopyrimidine compounds as PDE1 inhibitors > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,006,325 B2 - Document ID: US12006325B2 - Status: Granted - Kind: B2 - Application number: 17/902,730 - Filed: 2022-09-02 - Published: 2023-09-21 - Granted: 2024-06-11 - Earliest claimed: 2017-11-27 - Assignees: Dart NeuroScience, LLC - Applicants: Dart NeuroScience, LLC - Inventors: Brett Bookser; Iriny Botrous; Aaron Burns; DeMichael Chung; Brian Dyck; Andrew Kleinke; Dange Vijay Kumar; Margaret McCarrick; Nicholas Raffaele; Joe Tran; Michael Weinhouse - Web page: https://patentgrep.com/patent/US12006325B2 ## CPC - C07D 491/04: Ortho-condensed systems - C07D 491/048: the oxygen-containing ring being five-membered - A61P 25/16: Anti-Parkinson drugs - C07D 519/00: Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00 - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract Substituted furanopyrimidine chemical entities of Formula (I): wherein Ra has any of the values described herein, and compositions comprising such chemical entities; methods of making them; and their use in a wide range of methods, including metabolic and reaction kinetic studies; detection and imaging techniques; radioactive therapies; modulating and treating disorders mediated by PDE1 activity or dopaminergic signaling; treating neurological disorders, CNS disorders, dementia, neurodegenerative diseases, and trauma-dependent losses of function; treating stroke, including cognitive and motor deficits during stroke rehabilitation; facilitating neuroprotection and neurorecovery; enhancing the efficiency of cognitive and motor training, including animal skill training protocols; and treating peripheral disorders, including cardiovascular, renal, hematological, gastroenterological, liver, cancer, fertility, and metabolic disorders. ## Claims ### Claim 1 A pharmaceutical composition comprising: a pharmaceutically acceptable carrier; and a compound, or a pharmaceutically acceptable salt thereof, selected from group consisting of: 6-methyl-4-[(1-methylcyclopropyl)amino]-N-(1,3-thiazol-4-ylmethyl)furo[2,3-d]pyrimidine-5-carboxamide; 6-methyl-4-[(1-methylcyclopropyl)amino]-N-(1H-pyrrol-2-ylmethyl)furo[2,3-d]pyrimidine-5-carboxamide; N-[(2-fluorophenyl)methyl]-6-methyl-4-[(1-methylcyclopropyl)amino]furo[2,3-d]pyrimidine-5-carboxamide; N-[(5-cyclopropyl-1H-pyrazol-3-yl)methyl]-N,6-dimethyl-4-[(1-methylcyclopropyl)amino]furo[2,3-d]pyrimidine-5-carboxamide; and N-[(6-chloropyridin-3-yl)methyl]-6-methyl-4-[(1-methylcyclopropyl)amino]furo[2,3-d]pyrimidine-5-carboxamide. ### Claim 2 (depends on 1) The pharmaceutical composition of claim 1, wherein the compound is 6-methyl-4-[(1-methylcyclopropyl)amino]-N-(1H-pyrrol-2-ylmethyl)furo[2,3-d]pyrimidine-5-carboxamide, or a pharmaceutically acceptable salt thereof. ### Claim 3 A pharmaceutical composition comprising: a pharmaceutically acceptable carrier; and a compound, or a pharmaceutically acceptable salt thereof, selected from group consisting of: 6-methyl-N-{[5-(1-methyl-1H-pyrazol-4-yl)-1,2-oxazol-3-yl]methyl}-4-[(1-methylcyclopropyl)amino]furo[2,3-d]pyrimidine-5-carboxamide; 6-methyl-N-[(5-methyl-1,3-oxazol-2-yl)methyl]-4-[(1-methylcyclopropyl)amino]furo[2,3-d]pyrimidine-5-carboxamide; 6-methyl-4-[(1-methylcyclopropyl)amino]-N-[(5-methylpyrazin-2-yl)methyl]furo[2,3-d]pyrimidine-5-carboxamide; 6-methyl-N-[(5-methyl-1,3-thiazol-2-yl)methyl]-4-[(1-methylcyclopropyl)amino]furo[2,3-d]pyrimidine-5-carboxamide; and 6-methyl-4-[(1-methylcyclopropyl)amino]-N-{[5-(propan-2-yl)-1,3-oxazol-2-yl]methyl}furo[2,3-d]pyrimidine-5-carboxamide. ### Claim 4 (depends on 3) The pharmaceutical composition of claim 3, wherein the compound is 6-methyl-N-[(5-methyl-1,3-oxazol-2-yl)methyl]-4-[(1-methylcyclopropyl)amino]furo[2,3-d]pyrimidine-5-carboxamide, or a pharmaceutically acceptable salt thereof. ### Claim 5 A pharmaceutical composition comprising: a pharmaceutically acceptable carrier; and a compound, or a pharmaceutically acceptable salt thereof, selected from group consisting of: N-[(3-chloro-4-methoxyphenyl)methyl]-6-methyl-4-[(1-methylcyclopropyl)amino]furo[2,3-d]pyrimidine-5-carboxamide; N-{[1-(4-fluorophenyl)-1H-pyrazol-4-yl]methyl}-6-methyl-4-[(1-methylcyclopropyl)amino]furo[2,3-d]pyrimidine-5-carboxamide; N-{[1-(3-fluorophenyl)-1H-pyrazol-4-yl]methyl}-6-methyl-4-[(1-methylcyclopropyl)amino]furo[2,3-d]pyrimidine-5-carboxamide; N-[(6-methoxypyrimidin-4-yl)methyl]-6-methyl-4-[(1 methylcyclopropyl)amino]furo[2,3-d]pyrimidine-5-carboxamide; and N-[(6-methoxy-2-methylpyrimidin-4-yl)methyl]-6-methyl-4-[(1-methylcyclopropyl)amino]furo[2,3-d]pyrimidine-5-carboxamide. ### Claim 6 (depends on 1) The pharmaceutical composition of claim 1, wherein the compound is N-[(6-methoxypyrimidin-4-yl)methyl]-6-methyl-4-[(1 methylcyclopropyl)amino]furo[2,3-d]pyrimidine-5-carboxamide, or a pharmaceutically acceptable salt thereof. ### Claim 7 (depends on 2) A method of enhancing memory in a subject with a cognitive disorder, comprising administering to the subject an effective amount of a composition of claim 2. ### Claim 8 (depends on 7) The method of claim 7, wherein the cognitive disorder is Parkinson's disease. ### Claim 9 (depends on 4) A method of enhancing memory in a subject with a cognitive disorder, comprising administering to the subject an effective amount of a composition of claim 4. ### Claim 10 (depends on 9) The method of claim 9, wherein the cognitive disorder is Parkinson's disease. ### Claim 11 (depends on 6) A method of enhancing memory in a subject with a cognitive disorder, comprising administering to the subject an effective amount of a composition of claim 6. ### Claim 12 (depends on 11) The method of claim 11, wherein the cognitive disorder is Parkinson's disease. ### Claim 13 (depends on 8) The method of claim 8, wherein the cognitive disorder is Parkinson's disease with mild cognitive impairment (PD-MCI). ### Claim 14 (depends on 10) The method of claim 10, wherein the cognitive disorder is Parkinson's disease with mild cognitive impairment (PD-MCI). ### Claim 15 (depends on 5) A method of enhancing memory in a subject with a cognitive disorder, comprising administering to the subject an effective amount of a composition of claim 5. ### Claim 16 (depends on 12) The method of claim 12, wherein the cognitive disorder is Parkinson's disease with mild cognitive impairment (PD-MCI). ### Claim 17 (depends on 4) A method of treating a cognitive impairment in a subject with Parkinson's disease, comprising administering to the subject an effective amount of a composition of claim 4. ### Claim 18 (depends on 17) The method of claim 17, wherein the subject has Parkinson's disease with mild cognitive impairment (PD-MCI). ### Claim 19 (depends on 6) A method of treating a cognitive impairment in a subject with Parkinson's disease, comprising administering to the subject an effective amount of a composition of claim 6. ### Claim 20 (depends on 19) The method of claim 19, wherein the subject has Parkinson's disease with mild cognitive impairment (PD-MCI).