# US 11,078,207 B2 · Substituted pyrrolo[2,3-d]pyrimidines as HER2 inhibitors > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,078,207 B2 - Document ID: US11078207B2 - Status: Granted - Kind: B2 - Application number: 17/065,642 - Filed: 2020-10-08 - Published: 2021-01-28 - Granted: 2021-08-03 - Earliest claimed: 2019-01-11 - Assignees: Taiho Pharmaceutical Co., Ltd. - Applicants: Taiho Pharmaceutical Co., Ltd. - Inventors: Masayuki Nakamura; Takahiro Asai; Satoru Iguchi; Kei Oguchi - Web page: https://patentgrep.com/patent/US11078207B2 ## CPC - C07D 487/04: Ortho-condensed systems - A61P 35/00: Antineoplastic agents - A61P 35/04: specific for metastasis - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration} - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - 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 Provided are a novel pyrimidine compound that inhibits HER2 activity and exhibits brain penetration properties, or a salt thereof, and a pharmaceutical composition comprising the same. A compound represented by the following formula (I), or a salt thereof: wherein R1 represents a C1-C4 alkyl group optionally having a C1-C4 alkoxy group as a substituent, or a C3-C4 cycloalkyl group; R2 represents a hydrogen atom, a halogen atom, a C1-C6 alkyl group optionally having 1 to 5 C1-C4 alkoxy groups or fluorine atoms each as a substituent(s), or a C1-C6 alkoxy group; R3 represents a hydrogen atom, or a C1-C4 alkyl group optionally having 1 to 5 fluorine atoms as a substituent(s); R4 represents a hydrogen atom or a C1-C4 alkyl group; and R5 represents a phenyl group optionally having 1 to 3 substituents selected from fluorine atoms and chlorine atoms. ## Claims ### Claim 1 A compound represented by formula (I): or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein: R1 represents C1-C4 alkyl or C3-C4 cycloalkyl, wherein the C1-C4 alkyl is optionally substituted with 1 OC1—C4 alkyl substituent; R2 represents hydrogen, halogen, C1-C6 alkyl, or OC1—C6 alkyl, wherein the C1-C6 alkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of fluoro and OC1—C4 alkyl; R3 represents hydrogen or C1-C4 alkyl, wherein the C1-C4 alkyl is optionally substituted with 1, 2, 3, 4, or 5 fluoro substituents; R4 represents hydrogen or C1-C4 alkyl; and R5 represents phenyl, wherein the phenyl is optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of fluoro and chloro. ### Claim 2 (depends on 1) The compound according to claim 1, or a stereoisomer thereof, wherein the compound, or stereoisomer thereof, is represented by formula (II): or a pharmaceutically acceptable salt or tautomer thereof. ### Claim 3 (depends on 1) The compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein R1 represents methyl, tert-butyl, or cyclopropyl. ### Claim 4 (depends on 1) The compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein R2 represents C1-C6 alkyl, wherein the C1-C6 alkyl is optionally substituted with 1, 2, 3, 4, or 5 independently selected OC1—C4 alkyl substituents. ### Claim 5 (depends on 1) The compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein R2 represents methyl, ethyl, methoxymethyl, or ethoxymethyl. ### Claim 6 (depends on 1) The compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein R3 represents C1-C4 alkyl, wherein the C1-C4 alkyl is optionally substituted with 1, 2, 3, 4, or 5 fluoro substituents. ### Claim 7 (depends on 1) The compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein R3 represents methyl. ### Claim 8 (depends on 1) The compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein R4 represents hydrogen. ### Claim 9 (depends on 1) The compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein R5 represents phenyl, wherein the phenyl is optionally substituted with 1 or 2 substituents independently selected from the group consisting of fluoro and chloro. ### Claim 10 (depends on 1) The compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein R5 represents phenyl. ### Claim 11 (depends on 1) The compound according to claim 1, or a stereoisomer thereof, wherein the compound, or stereoisomer thereof, is selected from the group consisting of: or a pharmaceutically acceptable salt or tautomer thereof. ### Claim 12 (depends on 1) A pharmaceutical composition comprising a pharmaceutically acceptable carrier and the compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof. ### Claim 13 (depends on 12) The pharmaceutical composition according to claim 12, wherein the pharmaceutical composition is formulated for oral administration. ### Claim 14 (depends on 1) A method for treating a tumor in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of the compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof. ### Claim 15 (depends on 2) A method for treating a tumor in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of the compound, or a stereoisomer thereof, according to claim 2, or a pharmaceutically acceptable salt or tautomer thereof. ### Claim 16 (depends on 1) A method for treating a tumor in a subject, comprising orally administering to a subject in need thereof a therapeutically effective amount of the compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof. ### Claim 17 The compound: or a pharmaceutically acceptable salt or tautomer thereof. ### Claim 18 The compound: or a pharmaceutically acceptable salt or tautomer thereof. ### Claim 19 The compound: or a pharmaceutically acceptable salt or tautomer thereof.