Nitrogen-containing Aromatic Heterocyclic Compound

Content Provider	The Lens
Related Links	https://www.lens.org/lens/patent/011-249-332-965-195/frontpage
Language	English
Publisher Date	2019-08-21
Access Restriction	Open
Alternative Title	Stickstoffhaltige Aromatische Heterocyclische Verbindung Composé Hétérocyclique Aromatique Contenant De L'azote
Content Type	Text
Resource Type	Patent
Date Applied	2013-02-26
Agent	Hoffmann Eitle
Applicant	Astellas Pharma Inc Kotobuki Pharmaceutical Co Ltd
Application No.	13754501
Claim	A compound of formula (I) or a salt thereof: wherein X is N; Y is CH; L 1 is ethylene or -methylene-O-; Z is CH; R 1 , the same or different from one another, are -O-C 1-8 alkyl or halogen; p is 4; ring W is an optionally substituted pyrazole; Q is R 3 ; R 0 is C 1-8 alkyl optionally substituted with -OH; and R 3 is C 1-8 alkyl substituted with one or more groups selected from the group consisting of -C(O)OH, carbamoyl optionally substituted with one or two R 0 , -OH, an optionally substituted non-aromatic heterocyclic group, and -C(O)-(an optionally substituted non-aromatic heterocyclic group); or wherein X is N; Y is CH; L 1 is -methylene-O-; Z is CH; R 1 , the same or different from one another, are -O-methyl or F; p is 4; ring W is a benzene ring optionally substituted with -O-methyl; Q is -L 2 -R 2 ; L 2 is piperidine or 4-methylpiperazine; and R 2 is 4-methylpiperazine or 2-hydroxyethylamino. The compound according to Claim 1 or a salt thereof, wherein: X is N; Y is CH; L 1 is ethylene or -methylene-O-; Z is CH; R 1 , the same or different from one another, are -O-C 1-8 alkyl or halogen; p is 4; ring W is an optionally substituted pyrazole; Q is R 3 ; R 0 is C 1-8 alkyl optionally substituted with -OH; and R 3 is C 1-8 alkyl substituted with one or more groups selected from the group consisting of -C(O)OH, carbamoyl optionally substituted with one or two R 0 , -OH, an optionally substituted non-aromatic heterocyclic group, and -C(O)-(an optionally substituted non-aromatic heterocyclic group); The compound according to Claim 1 or a salt thereof, wherein: X is N; Y is CH; L 1 is -methylene-O-; Z is CH; R 1 , the same or different from one another, are -O-methyl or F; p is 4; ring W is a benzene ring optionally substituted with -O-methyl; Q is -L 2 -R 2; L 2 is piperidine or 4-methylpiperazine; and R 2 is 4-methylpiperazine or 2-hydroxyethylamino. The compound according to Claim 2 or a salt thereof, wherein R 3 is C 1-8 alkyl substituted with one or more substituents selected from the group consisting of -OH, a non-aromatic heterocyclic group optionally substituted with C 1-8 alkyl, and -C(O)-(a non-aromatic heterocyclic group optionally substituted with -OH). The compound according to Claim 4 or a salt thereof, wherein R 1 , the same or different from one another, are -O-methyl or F; L 1 is -methylene-O-; ring W is pyrazole optionally substituted with methyl; and R 3 is 2-hydroxyethyl, 2,3-dihydroxypropyl, or 4-methylpiperazin-1-ylmethy The compound according to Claim 1-3 or a salt thereof, wherein the compound is selected from the group consisting of: (2S)-3-[4-({5-[(2,6-difluoro-3,5-dimethoxybenzyl)oxy]pyrimidin-2-yl}amino)-1H-pyrazol-1-yl]propane-1,2-diol, 5-[(2,6-difluoro-3,5-dimethoxybenzyl)oxy]-N-{3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}pyrimidin-2-amine, 2-[4-({5-[(2,6-difluoro-3,5-dimethoxybenzyl)oxy]pyrimidin-2-yl}amino)-1H-pyrazol-1-yl]ethanol, 5-[(2,6-difluoro-3,5-dimethoxybenzyl)oxy]-N-{1-[2-(4-methylpiperazin-1-yl)ethyl]-1H-pyrazol-4-yl}pyrimidin-2-amine, 2-[4-({5-[(2,6-difluoro-3,5-dimethoxybenzyl)oxy]pyrimidin-2-yl}amino)-1H-pyrazol-1-yl]-1-(3-hydroxyazetidin-1-yl)ethanone, (2R)-3-[4-({5-[(2,6-difluoro-3,5-dimethoxybenzyl)oxy]pyrimidin-2-yl}amino)-1H-pyrazol-1-yl]propane-1,2-diol, and 5-[(2,6-difluoro-3,5-dimethoxybenzyl)oxy]-N-{1-methyl-5-[(4-methylpiperazin-1-yl)methyl]-1H-pyrazo1-3-yl}pyrimidin-2-amine. The compound according to Claim 6 or a salt thereof, wherein the compound is 5-[(2,6-difluoro-3,5-dimethoxybenzyl)oxy]-N-{3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}pyrimidin-2-amine. The compound according to Claim 6 or a salt thereof, wherein the compound is 2-[4-({5-[(2,6-difluoro-3,5-dimethoxybenzyl)oxy]pyrimidin-2-yl}amino)-1H-pyrazol-1-yl]ethano The compound according to Claim 6 or a salt thereof, wherein the compound is (2R)-3-[4-({5-[(2,6-difluoro-3,5-dimethoxybenzyl)oxy]pyrimidin-2-yl}amino)-1H-pyrazol-1-yl]propane-1,2-dio The compound according to Claim 6 or a salt thereof, wherein the compound is 5-[(2,6-difluoro-3,5-dimethoxybenzyl)oxy]-N-{1-methyl-5-[(4-methylpiperazin-1-yl)methyl]-1H-pyrazol-3-yl}pyrimidin-2-amine. A pharmaceutical composition comprising the compound according to Claims 1-10 or a salt thereof and a pharmaceutically acceptable excipient. The pharmaceutical composition according to Claim 11, which is used for treatment of mutant FGFR3-positive cancer. The compound according to Claims 1-10 or a salt thereof for use in a method for the treatment of mutant FGFR3-positive cancer. The compound for use according to Claim 13, wherein the cancer is mutant FGFR3-positive bladder cancer.
CPC Classification	HETEROCYCLIC COMPOUNDS Specific Therapeutic Activity Of Chemical Compounds Or Medicinal Preparations
Extended Family	108-459-596-913-746 024-155-037-544-720 155-307-446-586-438 140-071-286-856-802 165-054-209-619-865 094-761-572-893-614 049-560-180-684-28X 100-481-748-792-999 128-053-393-423-371 007-025-933-228-45X 179-981-233-309-109 040-629-477-318-307 011-249-332-965-195 052-554-998-416-545 084-414-260-708-601 144-410-964-505-112 079-861-620-353-60X 178-602-755-784-047 095-576-260-228-684 104-891-574-449-177 072-219-562-247-557 126-344-523-702-14X 100-283-265-901-794 074-025-734-843-548 020-441-716-835-29X 061-175-279-657-496 114-501-947-766-949 103-406-254-432-351 092-806-236-682-790 066-911-529-337-909 192-486-948-926-824 154-126-423-885-452 028-332-373-276-390 165-069-081-763-13X 028-295-860-964-027
Patent ID	2821402
Inventor/Author	Kameda Minoru Kuriwaki Ikumi Iikubo Kazuhiko Hisamichi Hiroyuki Kawamoto Yuichiro Moritomo Hiroyuki Suzuki Tomoyuki Futami Takashi Suzuki Atsushi Tsunoyama Kazuhisa Asaumi Makoto Tomiyama Hiroshi Noda Atsushi Iwai Yoshinori Tokuzaki Kazuo Okada Haruki Miyasaka Kozo
IPC	C07D239/42 A61K31/4545 A61K31/506 A61P35/00 A61P43/00 C07D239/47 C07D401/12 C07D401/14 C07D403/12 C07D405/14 C07D413/12 C07D471/10 C07D487/20
Status	Active
Owner	Astellas Pharma Inc. Kotobuki Pharmaceutical Co., Ltd.
Simple Family	108-459-596-913-746 024-155-037-544-720 155-307-446-586-438 140-071-286-856-802 165-054-209-619-865 094-761-572-893-614 049-560-180-684-28X 100-481-748-792-999 128-053-393-423-371 007-025-933-228-45X 179-981-233-309-109 040-629-477-318-307 011-249-332-965-195 052-554-998-416-545 084-414-260-708-601 144-410-964-505-112 079-861-620-353-60X 178-602-755-784-047 095-576-260-228-684 104-891-574-449-177 072-219-562-247-557 126-344-523-702-14X 100-283-265-901-794 074-025-734-843-548 020-441-716-835-29X 061-175-279-657-496 114-501-947-766-949 103-406-254-432-351 092-806-236-682-790 066-911-529-337-909 192-486-948-926-824 154-126-423-885-452 028-332-373-276-390 165-069-081-763-13X 028-295-860-964-027
CPC (with Group)	C07D403/12 C07D239/42 C07D239/47 C07D401/12 C07D401/14 C07D403/14 C07D405/12 C07D405/14 C07D413/12 C07D417/12 C07D417/14 C07D451/02 C07D451/04 C07D453/02 C07D471/10 C07D487/10 C07D491/107 A61P35/00 A61P43/00 C07D471/08
Issuing Authority	United States Patent and Trademark Office (USPTO)
Kind	Patent/Patent 1st level of publication/Inventor's certificate