US2022119386A1PendingUtilityA1
Fused ring derivative used as fgfr4 inhibitor
Assignee: JACOBIO PHARMACEUTICALS CO LTDPriority: Jul 27, 2018Filed: Sep 9, 2021Published: Apr 21, 2022
Est. expiryJul 27, 2038(~12 yrs left)· nominal 20-yr term from priority
A61P 35/00C07D 471/04A61K 31/4375C07D 519/00A61K 31/541A61K 31/496
68
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Claims
Abstract
A compound represented by formula I or a pharmaceutically acceptable salt thereof and a use thereof in preparing a drug for treating, stopping or preventing a disease or disorder mediated by FGFR4 activity.
Claims
exact text as granted — not AI-modified1 - 50 . (canceled)
51 . A compound of formula (I), or a pharmaceutically acceptable salt thereof:
wherein:
R 1 is selected from:
R 2 and R 3 are H;
is selected from:
52 . The compound of formula (I) or pharmaceutically acceptable salt thereof according to claim 51 , wherein R 1 is selected from:
53 . The compound of formula (I) or pharmaceutically acceptable salt thereof according to claim 52 , wherein R 1 is selected from:
54 . The compound of formula (I) or pharmaceutically acceptable salt thereof according to claim 51 , wherein
is selected from:
55 . The compound of formula (I) or pharmaceutically acceptable salt thereof according to claim 54 , wherein
is selected from:
56 . The compound of formula (I) or pharmaceutically acceptable salt thereof according to claim 51 , which is selected from:
Com-
pound
No.
Chemical Name
Structure Formula
1
N-(5-cyano-4-((2-(methylthio)ethyl)amino)pyridin-2-yl)-7-formyl-6-((4- methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine- 1(2H)-carboxamide
4
(R)-N-(5-cyano-4-((1-(methylthio)propan-2-yl)amino)pyridin-2-yl)-7- formyl-6-((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8- naphthyridine-1(2H)-carboxamide
6
N-(5-cyano-4-((2-methyl-2-(methylthio)propyl)amino)pyridin-2-yl)-7- formyl-6-((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8- naphthyridine-1(2H)-carboxamide
7
(R)-N-(5-cyano-4-((1-(methylthio)propan-2-yl)amino)pyridin-2-yl)-7- formyl-6-((2-oxopyrrolidine-1-yl)methyl)-3,4-dihydro-1,8- naphthyridine-1(2H)-carboxamide
8
(R)-N-(5-cyano-4-((2-(methylthio)ethyl)amino)pyridin-2-yl)-7-formyl-6- ((3-methoxy-2-oxopyrrolidin-1-yl)methyl)-3,4-dihydro-1,8- naphthyridine-1(2H)-carboxamide
9
N-(5-cyano-4-(((R)-1-(methylthio)propan-2-yl)amino)pyridin-2-yl)-7- formyl-6-(((R)-3-methoxy-2-oxopyrrolidin-1-yl)methyl)-3,4-dihydro-1,8- naphthyridine-1(2H)-carboxamide
13
(S)-N-(5-cyano-4-((2-(methylthio)ethyl)amino)pyridin-2-yl)-7-formyl-6- ((3-methoxy-2-oxopyrrolidin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine- 1(2H)-carboxamide
14
N-(5-cyano-4-((2-(methylthio)ethyl)amino)pyridin-2-yl)-7-formyl-6-((5- oxo-6-oxa-4-azaspiro[2.4]heptan-4-yl)methyl)-3,4-dihydro-1,8-naphthyridine- 1(2H)-carboxamide
15
N-(5-cyano-4-((2-(methylthio)ethyl)amino)pyridin-2-yl)-6-((4-cyclopropyl- 2-oxopiperazin-1-yl)methyl)-7-formyl-3,4-dihydro-1,8-naphthyridine- 1(2H)-carboxamide
16
N-(5-cyano-4-((2-(methylthio)ethyl)amino)pyridin-2-yl)-7-formyl-6-((2- oxo-1,3-oxazepan-3-yl)methyl)-3,4-dihydro-1,8-naphthyridine-1(2H)- carboxamide
19
N-(5-cyano-4-((2-((methyl-d3)thio)ethyl)amino)pyridin-2-yl)-7-formyl-6- ((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine- 1(2H)-carboxamide
23
N-(5-cyano-4-((2-(methylthio)ethyl)amino)pyridin-2-yl)-7-formyl-6-((2- oxopyrrolidin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carbox- amide
27
N-(5-cyano-4-((2-(methylsulfinyl)ethyl)amino)pyridin-2-yl)-7-formyl-6- ((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine- 1(2H)-carboxamide
31
N-(5-cyano-4-((2-(methylthio)ethyl)amino)pyridin-2-yl)-7-formyl-6-((4- methyl-2-oxopiperazin-1-yl)methyl-d2)-3,4-dihydro-1,8-naphthyridine- 1(2H)-carboxamide
62
N-(5-cyano-4-((2-((trifluoromethyl)thio)ethyl)amino)pyridin-2-yl)-7-formyl- 6-((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine- 1(2H)-carboxamide
64
N-(5-cyano-4-((3-(methylthio)propyl)amino)pyridin-2-yl)-7-formyl-6- ((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine- 1(2H)-carboxamide
69
N-(5-cyano-4-(((2R)-1-(methylsulfinyl)propan-2-yl)amino)pyridin-2-yl)- 7-formyl-6-((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8- naphthyridine-1(2H)-carboxamide
70
(R)-N-(5-cyano-4-((1-(methylthio)propan-2-yl)amino)pyridin-2-yl)-7- formyl-6-((2-oxo-1,3-oxozepan-3-yl)methyl)-3,4-dihydro-1,8-naphthyridine- 1(2H)-carboxamide
71
N-(5-cyano-4-((2-(ethylthio)ethyl)amino)pyridin-2-yl)-7-formyl-6-((4- methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine-1(2H)- carboxamide hydrochloride
72
N-(5-cyano-4-((2-(methylsulfonyl)ethyl)amino)pyridin-2-yl)-7-formyl-6- ((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine- 1(2H)-carboxamide hydrochloride
82
N-(5-cyano-4-((1-(methylthio)propan-2-yl)amino)pyridin-2-yl)-7-formyl- 6-((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine- 1(2H)-carboxamide
83
N-(5-cyano-4-(((2R)-1-(methylsulfonyl)propan-2-yl)amino)pyridin-2-yl)- 7-formyl-6-((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8- naphthyridine-1(2H)-carboxamide
57 . The compound of formula (I) or pharmaceutically acceptable salt thereof according to claim 56 , which is:
6
N-(5-cyano-4-((2-methyl-2-(methylthio)propyl)amino)pyridin-2-yl)-7- formyl-6-((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8- naphthyridine-1(2H)-carboxamide
58 . The compound of formula (I) or pharmaceutically acceptable salt thereof according to claim 56 , which is:
9
N-(5-cyano-4-(((R)-1-(methylthio)propan-2-yl)amino)pyridin-2-yl)-7- formyl-6-(((R)-3-methoxy-2-oxopyrrolidin-1-yl)methyl)-3,4-dihydro-1,8- naphthyridine-1(2H)-carboxamide
59 . The compound of formula (I) or pharmaceutically acceptable salt thereof according to claim 56 , which is:
62
N-(5-cyano-4-((2-((trifluoromethyl)thio)ethyl)amino)pyridin-2-yl)-7- formyl-6-((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8- naphthyridine-1(2H)-carboxamide
60 . The compound of formula (I) or pharmaceutically acceptable salt thereof according to claim 56 , which is:
64
N-(5-cyano-4-((3-(methylthio)propyl)amino)pyridin-2-yl)-7-formyl-6- ((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine- 1(2H)-carboxamide
61 . The compound of formula (I) or pharmaceutically acceptable salt thereof according to claim 56 , which is:
71
N-(5-cyano-4-((2-(ethylthio)ethyl)amino)pyridin-2-yl)-7-formyl-6-((4- methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine-1(2H)- carboxamide hydrochloride
62 . A pharmaceutical composition comprising the compound of formula (I) or pharmaceutically acceptable salt thereof according to claim 51 , and at least one pharmaceutically acceptable excipient.
63 . The pharmaceutical composition according to claim 62 , wherein the compound of formula (I) is:
6
N-(5-cyano-4-((2-methyl-2-(methylthio)propyl)amino)pyridin-2-yl)-7- formyl-6-((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8- naphthyridine-1(2H)-carboxamide
64 . The pharmaceutical composition according to claim 62 , wherein the compound of formula (I) is:
9
N-(5-cyano-4-(((R)-1-(methylthio)propan-2-yl)amino)pyridin-2-yl)-7- formyl-6-(((R)-3-methoxy-2-oxopyrrolidin-1-yl)methyl)-3,4-dihydro-1,8- naphthyridine-1(2H)-carboxamide
65 . The pharmaceutical composition according to claim 62 , wherein the compound of formula (I) is:
62
N-(5-cyano-4-((2-((trifluoromethyl)thio)ethyl)amino)pyridin-2-yl)-7- formyl-6-((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8- naphthyridine-1(2H)-carboxamide
66 . The pharmaceutical composition according to claim 62 , wherein the compound of formula (I) is:
64
N-(5-cyano-4-((3-(methylthio)propyl)amino)pyridin-2-yl)-7-formyl-6- ((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine- 1(2H)-carboxamide
67 . The pharmaceutical composition according to claim 62 , wherein the compound of formula (I) is:
71
N-(5-cyano-4-((2-(ethylthio)ethyl)amino)pyridin-2-yl)-7-formyl-6-((4- methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine-1(2H)- carboxamide hydrochloride
68 . A method for the treatment or prevention of a disease or condition mediated by FGFR4 activity, comprising administering to a subject a therapeutically effective amount of the compound of formula (I) or pharmaceutically acceptable salt thereof according to claim 51 .
69 . The method according to claim 68 , wherein the disease or condition mediated by FGFR4 activity is selected from one or more of liver cancer, head and neck cancer, esophageal cancer, stomach cancer, prostate cancer, ovarian cancer, lung cancer, breast cancer, colorectal cancer, rhabdomyoma, and a combination thereof.
70 . The method according to claim 68 , wherein the compound of formula (I) is:
4
(R)-N-(5-cyano-4-((1-(methylthio)propan-2-yl)amino)pyridin-2-yl)-7- formyl-6-((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8- naphthyridine-1(2H)-carboxamideJoin the waitlist — get patent alerts
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