US2023091810A1PendingUtilityA1
First-in-class of shmt2 and mthfd2 inhibitors as antitumor agents
Est. expiryAug 31, 2037(~11.1 yrs left)· nominal 20-yr term from priority
C07D 487/04A61K 31/519A61P 35/00
74
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
A compound of the Formula I and optionally a pharmaceutically acceptable salt thereof is provided:Formula I, wherein, R is one selected from the group consisting of H and CH3; n is an integer 4 when X is -CH2- and Ar is 1,4-phenyl, or n is an integer ranging from 1 to 4 when X is -CH2-and Ar is either 2'-fluoro-1,4-phenyl or 2,5-thienyl, or n is an integer ranging from 1 to 4 when X is one selected from the group consisting of O, S, -NH-, -NHCHO-, -NHCOCH3-, and -NHCOCF3- and Ar is one selected from the group consisting of (a) 1,4-phenyl, (b) 2'-fluoro-1,4-phenyl, and (c) 2,5-thienyl, or n is an integer 3 when X is -CH2-, R is CH3 and Ar is 1,4-phenyl.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A compound of Formula I, and optionally a pharmaceutically acceptable salt thereof:
wherein,
R is one selected from the group consisting of H and CH 3 ;
n is an integer 4 when X is -CH 2 - and Ar is 1,4-phenyl, or n is an integer ranging from 1 to 4 when X is -CH 2 - and Ar is either 2'-fluoro-1,4-phenyl or 2,5-thienyl, or
n is an integer ranging from 1 to 4 when X is one selected from the group consisting of O, S, -NH-, -NHCHO-, -NHCOCH 3 -, and -NHCOCF 3 - and Ar is one selected from the group consisting of (a) 1,4-phenyl, (b) 2'-fluoro-1,4-phenyl, and (c) 2,5-thienyl, or n is an integer 3 when X is -CH 2 -, R is CH 3 and Ar is 1,4-phenyl.
2 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula I, and optionally a pharmaceutically acceptable salt thereof:
wherein,
R is one selected from the group consisting of H and CH 3 ;
n is an integer 4 when X is -CH- and Ar is 1,4-phenyl, or n is an integer ranging from 1 to 4 when X is -CH 2 - and Ar is either 2'-fluoro-1,4-phenyl or 2,5-thienyl, or
n is an integer ranging from 1 to 4 when X is one selected from the group consisting of O, S, -NH-, -NHCHO-, -NHCOCH 3 -, and -NHCOCF 3 - and Ar is one selected from the group consisting of (a) 1,4-phenyl, (b) 2'-fluoro-1,4-phenyl, and (c) 2,5-thienyl, or n is an integer 3 when X is -CH 2 -, R is CH 3 and Ar is 1,4-phenyl.
3 . The pharmaceutical composition of claim 2 including a pharmaceutically acceptable carrier.
4 . A compound of Formula II, and optionally a pharmaceutically acceptable salt thereof:
wherein,
R is one selected from the group consisting of H and CH 3 ;
n is an integer ranging from 1 to 4; X is one selected from the group consisting of -CH 2 - , O, S, -NH-, -NHCHO-, -NHCOCH 3 -, and -NHCOCF 3 - .
5 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula II, and optionally a pharmaceutically acceptable salt thereof:
wherein,
R is one selected from the group consisting of H and CH 3 ;
n is an integer ranging from 1 to 4; X is one selected from the group consisting of -CH 2 - , O, S, -NH-, -NHCHO-, -NHCOCH 3 -, and -NHCOCF 3 - .
6 . The pharmaceutical composition of claim 5 including a pharmaceutically acceptable carrier.
7 . A compound of Formula III, and optionally a pharmaceutically acceptable salt thereof:
wherein,
R is one selected from the group consisting of H and CH 3 ;
n is an integer ranging from 1 to 4; X is one selected from the group consisting of CH and N; Y is one selected from the group consisting of CH and N; and Z is one selected from the group consisting of -CH 2 - , O, S, -NH-, -NHCHO-, -NHCOCH 3 -, and -NHCOCF 3 -.
8 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula III, and optionally a pharmaceutically acceptable salt thereof:
wherein,
R is one selected from the group consisting of H and CH 3 ;
n is an integer ranging from 1 to 4; X is one selected from the group consisting of CH and N; Y is one selected from the group consisting of CH and N; and Z is one selected from the group consisting of -CH 2 - , O, S, -NH-, -NHCHO-, -NHCOCH 3 -, and -NHCOCF 3 - .
9 . The pharmaceutical composition of claim 8 including a pharmaceutically acceptable carrier.
10 . A method of treating a patient having cancer comprising administering a therapeutically effective amount of a compound of Formula II, and optionally a pharmaceutically acceptable salt thereof:
wherein,
R is one selected from the group consisting of H and CH 3 ;
n is an integer ranging from 1 to 4; X is one selected from the group consisting of -CH 2 - , O, S, -NH-, -NHCHO-, -NHCOCH 3 -, and -NHCOCF 3 - .
11 . A method of treating a patient having cancer comprising administering a therapeutically effective amount of a compound of Formula III, and optionally a pharmaceutically acceptable salt thereof:
wherein,
R is one selected from the group consisting of H and CH 3 ;
n is an integer ranging from 1 to 4; X is one selected from the group consisting of CH and N; Y is one selected from the group consisting of CH and N; and Z is one selected from the group consisting of -CH 2 - , O, S, -NH-, -NHCHO-, -NHCOCH3-, and -NHCOCF 3 -.
12 . A method of targeting mitochondrial metabolism comprising administering to a cancer patient an effective amount of at least one compound selected from the group of Formula I, and optionally a pharmaceutically acceptable salt thereof, of Formula II, and optionally a pharmaceutically acceptable salt thereof, and of Formula III, and optionally a pharmaceutically acceptable salt thereof, of Formula III:
wherein,
R is one selected from the group consisting of H and CH 3 ;
n is an integer 4 when X is -CH 2 - and Ar is 1,4-phenyl, or n is an integer ranging from 1 to 4 when X is -CH 2 - and Ar is either 2'-fluoro-1,4-phenyl or 2,5-thienyl, or
n is an integer ranging from 1 to 4 when X is one selected from the group consisting of O, S, -NH-, -NHCHO-, -NHCOCH 3 -, and -NHCOCF 3 - and Ar is one selected from the group consisting of (a) 1,4-phenyl, (b) 2'-fluoro-1,4-phenyl, and (c) 2,5-thienyl, or n is an integer 3 when X is -CH 2 -, R is CH 3 and Ar is 1,4-phenyl; and
wherein,
R is one selected from the group consisting of H and CH 3 ; n is an integer ranging from 1 to 4; X is one selected from the group consisting of -CH 2 - , O, S, -NH-, -NHCHO-, -NHCOCH 3 -, and -NHCOCF 3 - ; and
wherein
R is one selected from the group consisting of H and CH 3 ;
n is an integer ranging from 1 to 4; X is one selected from the group consisting of CH and N; Y is one selected from the group consisting of CH and N; and Z is one selected from the group consisting of -CH 2 - , O, S, -NH-, -NHCHO-, -NHCOCH 3 -, and -NHCOCF 3 -.
13 . A method of targeting SHMT2 and MTHFD2 comprising administering to a cancer patient an effective amount of at least one compound selected from the group of Formula I, and optionally a pharmaceutically acceptable salt thereof, of Formula II, and optionally a pharmaceutically acceptable salt thereof, and of Formula III, and optionally a pharmaceutically acceptable salt thereof, of Formula III:
wherein,
R is one selected from the group consisting of H and CH 3 ; n is an integer 4 when X is -CH 2 - and Ar is 1,4-phenyl, or n is an integer ranging from 1 to 4 when X is -CH 2 - and Ar is either 2'-fluoro-1,4-phenyl or 2,5-thienyl, or n is an integer ranging from 1 to 4 when X is one selected from the group consisting of O, S, -NH-, -NHCHO-, -NHCOCH 3 -, and -NHCOCF 3 - and Ar is one selected from the group consisting of (a) 1,4-phenyl, (b) 2'-fluoro-1,4-phenyl, and (c) 2,5-thienyl, or n is an integer 3 when X is -CH 2 -, R is CH 3 and Ar is 1,4-phenyl; and
wherein, R is one selected from the group consisting of H and CH 3 ; n is an integer ranging from 1 to 4; X is one selected from the group consisting of -CH 2 - , O, S, -NH-, -NHCHO-, -NHCOCH 3 -, and -NHCOCF 3 - ; and
wherein R is one selected from the group consisting of H and CH 3 ; n is an integer ranging from 1 to 4; X is one selected from the group consisting of CH and N; Y is one selected from the group consisting of CH and N; and Z is one selected from the group consisting of -CH 2 -, O, S, -NH-, -NHCHO-, -NHCOCH 3 -, and -NHCOCF 3 - .
14 . The compound of claim 1 wherein n=4, Ar is 1,4-phenyl, R is CH 3 , and X is CH 2 and identified as compound AGF307.
15 . The compound of claim 1 wherein n=3, Ar is 2,5-thienyl, R is H, and X is CH 2 and identified as compound AGF318.
16 . The compound of claim 1 wherein n=4, Ar is 2,5-thienyl, R is H, and X is CH 2 and identified as compound AGF320.
17 . The compound of claim 1 wherein n=3, Ar is 1,4-phenyl, R is H, and X is O and identified as compound AGF323.
18 . The compound of claim 1 wherein n=2, Ar is 2,5-thienyl, R is H, and X is CH 2 and identified as compound AGF331.
19 . The compound of claim 1 wherein n=4, Ar is 1,4-phenyl, R is H, and X is CH 2 and identified as compound AGF299.
20 . The compound of claim 1 wherein n= 2, Ar is 2'-fluoro-1,4-phenyl, R is H, and X is CH 2 and identified as compound AGF359.
21 . The compound of claim 1 wherein n= 3, Ar is 2'-fluoro-1,4-phenyl, R is H, and X is CH 2 and identified as compound AGF347.
22 . The compound of claim 1 wherein n=4, Ar is 2'-fluoro-1,4-phenyl, R is H, and X is CH 2 and identified as compound AGF355.Join the waitlist — get patent alerts
Track US2023091810A1 — get alerts on status changes and closely related new filings.
We store only your email — no account needed. See our privacy policy.