# US 11,896,597 B2 · ErbB/BTK inhibitors > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,896,597 B2 - Document ID: US11896597B2 - Status: Granted - Kind: B2 - Application number: 18/045,838 - Filed: 2022-10-12 - Published: 2023-09-21 - Granted: 2024-02-13 - Earliest claimed: 2018-01-31 - Assignees: Dizal (Jiangsu) Pharmaceutical Co., Ltd. - Applicants: Dizal (Jiangsu) Pharmaceutical Co., Ltd. - Inventors: Zhenfan Yang; Xiaolin Zhang - Web page: https://patentgrep.com/patent/US11896597B2 ## CPC - A61K 31/53: having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine (melarsoprol A61K31/555 {; with four nitrogen atoms A61K31/495}) - A61K 31/505: Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim - A61K 31/506: not condensed and containing further heterocyclic rings - C07D 239/48: Two nitrogen atoms - C07D 251/48: Two nitrogen atoms - C07D 401/12: linked by a chain containing hetero atoms as chain links - C07D 403/12: linked by a chain containing hetero atoms as chain links - C07D 405/12: linked by a chain containing hetero atoms as chain links - C07D 487/04: Ortho-condensed systems - 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) - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) ## Abstract Disclosed are compounds inhibiting ErbBs (e.g., EGFR or Her 2), especially mutant forms of ErbBs, and BTK, pharmaceutically acceptable salts, hydrates, solvates or stereoisomers thereof and pharmaceutical compositions comprising the compounds. The compound and the pharmaceutical composition can effectively treat ErbBs (especially mutant forms of ErbBs) or BTK associated diseases, including cancer. ## Claims ### Claim 1 A method of treating an ErbB associated disease in a subject, comprising administering to the subject about 50 mg to about 500 mg per day of (R)—N-(5-(4-(5-chloro-4-fluoro-2-(2-hydroxypropan-2-yl)phenylamino)pyrimidin-2-ylamino)-2-(3-(dimethylamino)pyrrolidin-1-yl)-4-methoxyphenyl)acrylamide, or a pharmaceutically acceptable salt, hydrate, solvate or stereoisomer thereof, wherein the ErbB associated disease is lung cancer. ### Claim 2 (depends on 1) The method according to claim 1, wherein the subject is a warm blooded-animal. ### Claim 3 (depends on 2) The method according to claim 2, wherein the warm blooded-animal is man. ### Claim 4 (depends on 1) The method according to claim 1, wherein the subject is a non-small cell lung cancer patient with EGFR exon20 insertion mutations. ### Claim 5 (depends on 4) The method according to claim 4, wherein the patient is pretreated by platinum-based chemotherapy. ### Claim 6 (depends on 5) The method according to claim 5, wherein the patient has brain metastasis. ### Claim 7 (depends on 1) The method according to claim 1, wherein the lung cancer is non-small cell lung cancer. ### Claim 8 (depends on 1) The method according to claim 1, wherein the lung cancer is non-small cell lung cancer with central nervous system metastasis. ### Claim 9 (depends on 1) The method according to claim 1, wherein the lung cancer is non-small cell lung cancer with brain metastasis. ### Claim 10 (depends on 1) The method according to claim 1, wherein the lung cancer is non-small cell lung cancer with EGFR exon20 insertion mutations. ### Claim 11 (depends on 10) The method according to claim 10, comprising administering to the subject about 100 mg, about 200 mg, about 300 mg or about 400 mg per day of (R)—N-(5-(4-(5-chloro-4-fluoro-2-(2-hydroxypropan-2-yl)phenylamino)pyrimidin-2-ylamino)-2-(3-(dimethylamino)pyrrolidin-1-yl)-4-methoxyphenyl)acrylamide, or a pharmaceutically acceptable salt, hydrate, solvate or stereoisomer thereof. ### Claim 12 (depends on 1) The method according to claim 1, wherein the lung cancer is non-small cell lung cancer with EGFR exon19 deletion mutation, EGFR L858R mutation, EGFR exon 19 deletion/L858R and T790M double mutations, or less common EGFR non-resistant mutation selected from the group consisting of Gly719Xaa, Leu861Gln, and Ser768Ile mutation. ### Claim 13 (depends on 12) The method according to claim 12, comprising administering to the subject about 50 mg to about 500 mg per day of (R)—N-(5-(4-(5-chloro-4-fluoro-2-(2-hydroxypropan-2-yl)phenylamino)pyrimidin-2-ylamino)-2-(3-(dimethylamino)pyrrolidin-1-yl)-4-methoxyphenyl)acrylamide, or a pharmaceutically acceptable salt, hydrate, solvate or stereoisomer thereof. ### Claim 14 (depends on 1) The method according to claim 1, wherein (R)—N-(5-(4-(5-chloro-4-fluoro-2-(2-hydroxypropan-2-yl)phenylamino)pyrimidin-2-ylamino)-2-(3-(dimethylamino)pyrrolidin-1-yl)-4-methoxyphenyl)acrylamide, or a pharmaceutically acceptable salt, hydrate, solvate or stereoisomer thereof is administered to the subject orally. ### Claim 15 A pharmaceutical composition formulated in a unit-dosage form comprising about 50 mg-about 500 mg (R)—N-(5-(4-(5-chloro-4-fluoro-2-(2-hydroxypropan-2-yl)phenylamino)pyrimidin-2-ylamino)-2-(3-(dimethylamino)pyrrolidin-1-yl)-4-methoxyphenyl)acrylamide, or a pharmaceutically acceptable salt, hydrate, solvate or stereoisomer thereof. ### Claim 16 (depends on 15) The composition according to claim 15, comprising about 50 mg, about 100 mg, about 200 mg, about 300 mg, about 400 mg or about 500 mg (R)—N-(5-(4-(5-chloro-4-fluoro-2-(2-hydroxypropan-2-yl)phenylamino)pyrimidin-2-ylamino)-2-(3-(dimethylamino)pyrrolidin-1-yl)-4-methoxyphenyl)acrylamide, or a pharmaceutically acceptable salt, hydrate, solvate or stereoisomer thereof. ### Claim 17 (depends on 15) The composition according to claim 15 formulated in a unit-dosage form for oral administration. ### Claim 18 A pharmaceutical composition comprising about 50 mg-about 500 mg (R)—N-(5-(4-(5-chloro-4-fluoro-2-(2-hydroxypropan-2-yl)phenylamino)pyrimidin-2-ylamino)-2-(3-(dimethylamino)pyrrolidin-1-yl)-4-methoxyphenyl)acrylamide, or a pharmaceutically acceptable salt, hydrate, solvate or stereoisomer thereof. ### Claim 19 (depends on 18) The composition according to claim 18, comprising about 50 mg, about 100 mg, about 200 mg, about 300 mg, about 400 mg or about 500 mg (R)—N-(5-(4-(5-chloro-4-fluoro-2-(2-hydroxypropan-2-yl)phenylamino)pyrimidin-2-ylamino)-2-(3-(dimethylamino)pyrrolidin-1-yl)-4-methoxyphenyl)acrylamide, or a pharmaceutically acceptable salt, hydrate, solvate or stereoisomer thereof. ### Claim 20 (depends on 18) The composition according to claim 18 formulated for oral administration.