US2019167820A1PendingUtilityA1
Novel aryl ethene derivative and pharmaceutical composition containing same as active ingredient
Est. expiryJun 27, 2036(~9.9 yrs left)· nominal 20-yr term from priority
Inventors:Sung Yeoun HwangSung Jin ChoJina KimJungwook ChinHayoung HwangIn-Kyu LeeYong Hyun JeonJaetae LeeJae-Han JeonSang-Wook Kim
A61K 31/454A61K 31/407C07D 241/04C07D 203/08A61K 31/5375A61K 31/403A61K 31/496A61K 31/495A61K 31/396A61K 31/40A61K 31/4192A61K 31/695A61K 31/445A61K 31/535A61K 31/404A61P 35/00A61K 31/397C07D 265/28A61K 51/025
48
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
The present invention relates to an aryl ethene derivative, for inhibiting an estrogen-related receptor gamma (ERRγ) activity, a prodrug of same, a solvate of same, a stereoisomer of same or pharmaceutically acceptable salts of same, and a pharmaceutical composition containing same as an active ingredient.
Claims
exact text as granted — not AI-modified1 . A pharmaceutical composition for treating thyroid cancer, comprising: the arylethene derivative represented by the following Chemical Formula 1:
wherein
L is (C6-C20)arylene, (C3-C20)heteroarylene, or (C3-C20)fused heterocycle;
R 1 is (C3-C20)heterocycloalkyl, (C3-C20)heteroaryl, —O—(CH 2 ) m —R 11 , —(CH 2 ) m —R 12 , —NH—(CH 2 ) m —R 13 , —NHCO—(CH 2 ) n —R 14 , or —SiR 16 R 17 —(CH 2 ) m —R 15 ;
R 11 to R 15 are independently of one another (C3-C20)heterocycloalkyl;
R 16 and R 17 are independently of each other (C1-C20)alkyl;
m is an integer of 1 to 3; and
n is an integer of 0 or 1;
Ar is (C6-C20)aryl or (C3-C20)heteroaryl, in which the aryl or heteroaryl of Ar may be further substituted by one or more selected from the group consisting of hydroxy, halogen, (C1-C20)alkyl, halo(C1-C20)alkyl, (C1-C20)alkoxy, nitro, cyano, —NR 21 R 22 , (C1-C20)alkylcarbonyloxy, (C1-C20)alkylcarbonylamino, guanidino, —SO 2 —R 23 , and —OSO 2 —R 24 ;
R 21 and R 22 are independently of each other hydrogen, (C1-C20)alkylsulfonyl, or (C3-C20)cycloalkylsulfonyl;
R 23 and R 24 are independently of each other (C1-C20)alkyl, halo(C1-C20)alkyl, or (C3-C20)cycloalkyl;
R 2 is hydroxy, halogen, (C1-C20)alkylcarbonyloxy, or (C1-C20)alkylsulfonyloxy;
the heterocycloalkyl or heteroaryl of R 1 and the heterocycloalkyl of R 11 to R 15 may be further substituted by one or more selected from the group consisting of (C1-C20)alkyl, (C3-C20)cycloalkyl, (C2-C20)alkenyl, amidino, (C1-C20)alkoxycarbonyl, hydroxy, hydroxy(C1-C20)alkyl, and di(C1-C20)alkylamino(C1-C20)alkyl; and
the heterocycloalkyl and heteroaryl contains one or more heteroatoms selected from the group consisting of N, O and S, and the heterocycloalkyl is a saturated or unsaturated mono-, bi-, or spirocycle having a carbon atom or nitrogen atom in a ring as a binding site,
or a prodrug, solvate, stereoisomer, or pharmaceutically acceptable salt thereof, as an effective component, and a pharmaceutically acceptable carrier, and being used in combination of radioactive iodine.
2 . The pharmaceutical composition of claim 1 , wherein the thyroid cancer is analpastic thyroid cancer.
3 . The pharmaceutical composition of claim 1 , wherein the arylethene derivative is an arylethene derivative represented by the following Chemical Formulae 2 to 5:
wherein denotes a single bond or a double bond; and R 1 , Ar and R 2 are as defined in claim 1 .
4 . The pharmaceutical composition of claim 1 , wherein
R 1 is (C3-CO 1 )heterocycloalkyl, (C3-C10)heteroaryl, —O—(CH 2 ) m —R 11 , —(CH 2 ) m —R 12 , —NH—(CH 2 ) m —R 13 , —NHCO—(CH 2 ) n —R 14 , or —SiR 16 R 17 —(CH 2 ) m —R 15 ; R 11 to R 15 are independently of one another (C3-C10)heterocycloalkyl; R 16 and R 17 are independently of each other (C1-C10)alkyl; m is an integer of 1 to 3; n is an integer of 0 or 1; Ar is (C6-C12)aryl or (C3-C12)heteroaryl, in which the aryl or heteroaryl of Ar may be further substituted by one or more selected from the group consisting of hydroxy, halogen, (C1-C10)alkyl, halo(C1-C10)alkyl, (C1-C10)alkoxy, nitro, cyano, amino, (C1-C10)alkylsulfonylamino, (C3-C10)cycloalkylsulfonylamino, di((C1-C10)alkylsulfonyl)amino, (C1-C10)alkylcarbonyloxy, (C1-C10)alkylcarbonylamino, guanidino, (C1-C10)alkylsulfonyl, (C1-C10)alkylsulfonyloxy, halo(C1-C10)alkylsulfonyloxy, and (C3-C10)cycloalkylsulfonyloxy; R 2 is hydroxy, fluoro, (C1-C10)alkylcarbonyloxy, or (C1-C10)alkylsulfonyloxy; and the heterocycloalkyl or heteroaryl of R 1 and the heterocycloalkyl of R 11 to R 15 may be further substituted by one or more selected from the group consisting of (C1-C10)alkyl, (C3-C10)cycloalkyl, (C2-C10)alkenyl, amidino, (C1-C10)alkoxycarbonyl, hydroxy(C1-C10)alkyl, and di(C1-C10)alkylamino(C1-C10)alkyl.
5 . The pharmaceutical composition of claim 4 , wherein
R 1 is (C3-C10)heterocycloalkyl or —O—(CH 2 ) m —R 11 ; R 11 is (C3-C10)heterocycloalkyl; m is an integer of 1 to 3; and the heterocycloalkyl of R 1 and R 11 may be further substituted by one or more selected from the group consisting of (C1-C10)alkyl, (C3-C10)cycloalkyl, (C2-C10)alkenyl, amidino, (C1-C10)alkoxycarbonyl, hydroxy(C1-C10)alkyl, and di(C1-C10)alkylamino(C1-C10)alkyl.
6 . The pharmaceutical composition of claim 1 , wherein the heterocycloalkyl of R 1 and R 11 to R 15 is independently of each other selected from the following structures:
wherein R 31 and R 32 are independently of each other hydrogen, (C1-C10)alkyl, (C3-C10)cycloalkyl, (C2-C10)alkenyl, amidino, (C1-C10)alkoxycarbonyl, hydroxy(C1-C10)alkyl, or di(C1-C10)alkylamino(C1-C10)alkyl; and L is O or S.
7 . The pharmaceutical composition of claim 3 , wherein the arylethene derivative is an arylethene derivative represented by the following Chemical Formula 6:
wherein
R 1 is (C3-C10)heterocycloalkyl or —O—(CH 2 ) m —R 1 ;
R 11 is (C3-C10)heterocycloalkyl;
m is an integer of 1 to 3;
the heterocycloalkyl of R 1 and R 11 may be further substituted by one or more selected from the group consisting of (C1-C10)alkyl, (C3-C10)cycloalkyl, (C2-C10)alkenyl, amidino, (C1-C10)alkoxycarbonyl, hydroxy(C1-C10)alkyl, and di(C1-C20)alkylamino(C1-C20)alkyl;
Ar is (C6-C12)aryl or (C3-C12)heteroaryl, in which the aryl or heteroaryl of Ar may be further substituted by one or more selected from the group consisting of hydroxy, halogen, (C1-C10)alkyl, halo(C1-C10)alkyl, (C1-C10)alkoxy, nitro, cyano, amino, (C1-C10)alkylsulfonylamino, (C3-C10)cycloalkylsulfonylamino, di((C1-C10)alkylsulfonyl)amino, (C1-C10)alkylcarbonyloxy, (C1-C10)alkylcarbonylamino, guanidino, (C1-C10)alkylsulfonyl, (C1-C10)alkylsulfonyloxy, halo(C1-C10)alkylsulfonyloxy, and (C3-C10)cycloalkylsulfonyloxy; and
R 2 is hydroxy, fluoro, (C1-C10)alkylcarbonyloxy, or (C1-C10)alkylsulfonyloxy.
8 . The pharmaceutical composition of claim 7 , wherein R 2 is hydroxy; and R 1 is heterocycloalkyl selected from the following structures:
wherein R 31 and R 32 are independently of each other hydrogen, (C1-C10)alkyl, (C3-C10)cycloalkyl, (C2-C10)alkenyl, amidino, (C1-C10)alkoxycarbonyl, hydroxy(C1-C10)alkyl, or di(C1-C10)alkylamino(C1-C10)alkyl; and L is O or S.
9 . The pharmaceutical composition of claim 7 , wherein R 2 is hydroxy; R 1 is —O—(CH 2 ) m —R 11 ; m is an integer of 1 or 2; and R 11 is heterocycloalkyl selected from the following structures:
wherein R 31 and R 32 are independently of each other halogen, (C1-C100)alkyl, (C1-C10)alkoxycarbonyl, or hydroxy(C1-C10)alkyl; and L is O or S.
10 . The pharmaceutical composition of claim 3 , wherein the arylethene derivative is selected from the following structures:
11 . The pharmaceutical composition of claim 7 , wherein the arylethene derivative is selected from the following structures:
12 . A kit for treating thyroid cancer, comprising: an arylethene derivative represented by the following Chemical Formula 1:
wherein
L is (C6-C20)arylene, (C3-C20)heteroarylene, or (C3-C20)fused heterocycle;
R 1 is (C3-C20)heterocycloalkyl, (C3-C20)heteroaryl, —O—(CH 2 ) m —R 11 , —(CH 2 ) m —R 12 , —NH—(CH 2 ) m —R 13 , —NHCO—(CH 2 ) n —R 14 , or —SiR 16 R 17 —(CH 2 ) m —R 15 ;
R 11 to R 15 are independently of one another (C3-C20)heterocycloalkyl;
R 16 and R 17 are independently of each other (C1-C20)alkyl;
m is an integer of 1 to 3;
n is an integer of 0 or 1;
Ar is (C6-C20)aryl or (C3-C20)heteroaryl, in which the aryl or heteroaryl of Ar may be further substituted by one or more selected from the group consisting of hydroxy, halogen, (C1-C20)alkyl, halo(C1-C20)alkyl, (C1-C20)alkoxy, nitro, cyano, —NR 21 R 22 , (C1-C20)alkylcarbonyloxy, (C1-C20)alkylcarbonylamino, guanidino, —SO 2 —R 23 and —OSO 2 —R 24 ;
R 21 and R 22 are independently of each other hydrogen, (C1-C20)alkylsulfonyl, or (C3-C20)cycloalkylsulfonyl;
R 23 and R 24 are independently of each other (C1-C20)alkyl, halo(C1-C20)alkyl, or (C3-C20)cycloalkyl;
R 2 is hydroxy, halogen, (C1-C20)alkylcarbonyloxy, or (C1-C20)alkylsulfonyloxy;
the heterocycloalkyl or heteroaryl of R 1 and the heterocycloalkyl of R 11 to R 15 may be further substituted by one or more selected from the group consisting of (C1-C20)alkyl, (C3-C20)cycloalkyl, (C2-C20)alkenyl, amidino, (C1-C20)alkoxycarbonyl, hydroxy, hydroxy(C1-C20)alkyl, and di(C1-C20)alkylamino(C1-C20)alkyl; and
the heterocycloalkyl and heteroaryl contains one or more heteroatoms selected from the group consisting of N, O and S, and the heterocycloalkyl is a saturated or unsaturated mono-, bi-, or spirocycle having a carbon atom or nitrogen atom in a ring as a binding site,
or a prodrug, solvate, stereoisomer, or pharmaceutically acceptable salt thereof, and radioactive iodine.Join the waitlist — get patent alerts
Track US2019167820A1 — get alerts on status changes and closely related new filings.
We store only your email — no account needed. See our privacy policy.