# US 2013/0158259 A1 · 2-aminopyrimidine modulators of the histamine h4 receptor > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2013/0158259 A1 - Document ID: US20130158259A1 - Status: Published application - Kind: A1 - Application number: 13/766,375 - Filed: 2013-02-13 - Published: 2013-06-20 - Earliest claimed: 2007-02-14 - Assignees: Janssen Pharmaceutica NV - Inventors: Hui CAI; Frank CHAVEZ; James P. EDWARDS; Annie E. FITZGERALD; Jing LIU; NEELAKANDHA S. MANI; Michele C. RIZZOLIO; Brad M. SAVALL; Deborah M. SMITH; Jennifer D. VENABLE; Jianmei WEI; Danielle K. WIENER; Ronald L. WOLIN - Web page: https://patentgrep.com/patent/US20130158259A1 ## CPC - A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis - C07D 498/04: Ortho-condensed systems - A61P 11/00: Drugs for disorders of the respiratory system - A61P 11/06: Antiasthmatics - A61P 17/00: Drugs for dermatological disorders - A61P 17/04: Antipruritics - A61P 19/02: for joint disorders, e.g. arthritis, arthrosis - A61P 27/14: Decongestants or antiallergics - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - A61P 37/00: Drugs for immunological or allergic disorders - A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection - A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C07D 239/48: Two nitrogen atoms - C07D 239/70: condensed with carbocyclic rings or ring systems - C07D 239/95: with hetero atoms directly attached in positions 2 and 4 - C07D 401/04: directly linked by a ring-member-to-ring-member bond - C07D 403/04: directly linked by a ring-member-to-ring-member bond - C07D 405/04: directly linked by a ring-member-to-ring-member bond - C07D 405/14: containing three or more hetero rings - C07D 409/14: containing three or more hetero rings - C07D 471/04: Ortho-condensed systems - C07D 487/04: Ortho-condensed systems - C07D 487/08: Bridged systems - C07D 487/10: Spiro-condensed systems - 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 - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) ## Abstract 2-Aminopyrimidine compounds are described, which are useful as H4 receptor modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by H4 receptor activity, such as allergy, asthma, autoimmune diseases, and pruritis. ## Claims ### Claim 1 A chemical entity selected from compounds of Formula (I): wherein R1 and R2 taken together form —(CH2)3-5—; and —N(R3)R4 is one of the following moieties: where q is 0 or 1; R3 and R4 are taken together as defined by the structure of each one of such moieties; Ra is H or OH; Rb and Rc are each independently H or C1-3alkyl; and pharmaceutically acceptable salts of compounds of Formula (I). ### Claim 2 (depends on 1) A chemical entity as in claim 1, wherein R1 and R2 taken together form —(CH2)4—. ### Claim 3 (depends on 1) A chemical entity as in claim 1, wherein —N(R3)R4 is: where q is 0. ### Claim 4 (depends on 1) A chemical entity as in claim 1, wherein —N(R3)R4 is: ### Claim 5 (depends on 1) A chemical entity as in claim 1, wherein —N(R3)R4 is: ### Claim 6 (depends on 1) A chemical entity as in claim 1, wherein —N(R3)R4 is: ### Claim 7 (depends on 1) A chemical entity as in claim 1, wherein —N(R3)R4 is: ### Claim 8 (depends on 1) A chemical entity as in claim 1, wherein —N(R3)R4 is: ### Claim 9 (depends on 1) A chemical entity as in claim 1, wherein Ra is H. ### Claim 10 (depends on 1) A chemical entity as in claim 1, wherein Rb and Rc are each independently H or methyl. ### Claim 11 An chemical entity selected from: 4-(4-Methyl-piperazin-1-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine; 4-(4-piperazin-1-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine; (R)-4-(3-Amino-pyrrolidin-1-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine; (R)-4-(3-Methylamino-pyrrolidin-1-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine; (R,R)-4-(Hexahydro-pyrrolo[3,4-b]pyrrol-5-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine; 4-(cis-Octahydro-pyrrolo[3,4-b]pyridin-6-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine; (R,R)-4-(Octahydro-pyrrolo[3,4-b]pyridin-6-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine; (S,S)-4-(2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine; 4-(4-Methyl-piperazin-1-yl)-6,7-dihydro-5H-cyclopentapyrimidin-2-ylamine; (R)-4-(3-Methylamino-pyrrolidin-1-yl)-6,7-dihydro-5H-cyclopentapyrimidin-2-ylamine; and pharmaceutically acceptable salts thereof. ### Claim 12 (depends on 1) An chemical entity as in claim 1, wherein said chemical entity is a compound of Formula (I) or a pharmaceutically acceptable salt of said compound of Formula (I). ### Claim 13 A pharmaceutical composition, comprising an effective amount of at least one chemical entity selected from compounds of Formula (I): wherein R1 and R2 taken together form (CH2)3-5; —N(R3)R4 is one of the following moieties: where q is 0 or 1; R3 and R4 are taken together as defined by the structure of each one of such moieties; Ra is H or OH; Rb and Rc are each independently H or C1-3alkyl; and pharmaceutically acceptable salts of compounds of Formula (I). ### Claim 17 (depends on 16) A pharmaceutical composition as in claim 16, wherein said chemical entity is selected from: 4-(4-Methyl-piperazin-1-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine; 4-(4-piperazin-1-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine; (R)-4-(3-Amino-pyrrolidin-1-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine; (R)-4-(3-Methylamino-pyrrolidin-1-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine; (R,R)-4-(Hexahydro-pyrrolo[3,4-b]pyrrol-5-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine; 4-(cis-Octahydro-pyrrolo[3,4-b]pyridin-6-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine; (R,R)-4-(Octahydro-pyrrolo[3,4-b]pyridin-6-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine; (S,S)-4-(2,5-Diaza-bicyclo[2.2.1]hept-2-yl)-5,6,7,8-tetrahydro-quinazolin-2-ylamine; 4-(4-Methyl-piperazin-1-yl)-6,7-dihydro-5H-cyclopentapyrimidin-2-ylamine; (R)-4-(3-Methylamino-pyrrolidin-1-yl)-6,7-dihydro-5H-cyclopentapyrimidin-2-ylamine; and pharmaceutically acceptable salts thereof.