Granted Patent
B2
US 12,227,503 · App. 18/241,583 · Granted Feb 18, 2025
Compositions and methods for modulating hair growth
Inventors:
William E. Lowry (Los Angeles, CA); Michael E. Jung (Los Angeles, CA); Heather R. Christofk (Los Angeles, CA); Xiaoguang Liu (Santa Monica, CA); Aimee Flores (Los Angeles, CA)
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Abstract
The present disclosure relates to compounds that are capable of inhibiting the mitochondrial pyruvate carrier and promoting hair growth. The disclosure further relates to methods of promoting hair growth or treating conditions or disorders affecting hair growth, such as baldness or alopecia.
Claims (40)
1. A compound of formula I or a pharmaceutically acceptable salt thereof:
wherein:
each A is independently CH, CR 4 , or N;
Y is carboxyl, ester, amide, or
R 2 is CN;
R 3 is aralkyl substituted by two R 5 in the meta positions, wherein each R 5 is independently selected from alkyl, alkoxy, and halo;
each R 4 is independently alkyl, carboxyl, halo, hydroxy, ester, or CN;
R 7 is hydrogen, alkyl, halo, hydroxyl, alkoxy, or acyloxy; and
R 10 is hydrogen or alkyl.
2. The compound of claim 1 , wherein the compound has a structure represented by formula III or a pharmaceutically acceptable salt thereof:
wherein,
Y is carboxyl, ester, amide, or
R 2 is CN;
R 3 is aralkyl substituted by two R 5 in the meta positions, wherein each R 5 is independently selected from alkyl, alkoxy, and halo;
each R 4 is independently alkyl, carboxyl, halo, hydroxy, ester, or CN;
R 7 is hydrogen, alkyl, halo, hydroxyl, alkoxy, or acyloxy; and
R 10 is hydrogen or alkyl.
3. The compound of claim 1 , wherein Y is carboxyl, ester, or amide.
4. The compound of claim 1 , wherein the compound has a structure represented by formula V or a pharmaceutically acceptable salt thereof:
wherein:
each A is independently CH, CR 4 , or N;
X is NR 6 or O;
R 1 is H or lower alkyl; or either R 1 and R 6 or R 1 and R 2 , together with the atoms that separate them, complete a heterocycle;
R 2 is CN;
R 3 is aralkyl substituted by two R 5 in the meta positions, wherein each R 5 is independently selected from alkyl, alkoxy, and halo;
each R 4 is independently alkyl, carboxyl, halo, hydroxy, or CN;
R 6 is H, alkyl, or cycloalkyl;
R 7 is hydrogen, alkyl, halo, hydroxyl, alkoxy, or acyloxy; and
n is 0-4.
5. The compound of claim 1 , wherein at least one A is N.
6. The compound of claim 4 , wherein X is NH or O.
7. The compound of claim 4 , wherein R 1 is H or lower alkyl.
8. The compound of claim 1 , wherein each R 5 is independently selected from fluoroalkyl or fluoro.
9. The compound of claim 4 , wherein the compound is represented by formula Vb:
wherein n is 0-3.
10. The compound of claim 9 , wherein n is 0 or 1.
11. The compound of claim 1 , wherein R 4 is halo or haloalkyl.
12. The compound of claim 1 , wherein R 7 is hydrogen, hydroxyl, halo, or acyloxy.
13. A compound selected from:
or a pharmaceutically acceptable salt thereof.
Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Oct 31, 2023
From: LOWRY, WILLIAM E.; JUNG, MICHAEL E.; CHRISTOFK, HEATHER; LIU, XIAOGUANG
To: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Reel/Frame 065402/0251 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Oct 31, 2023
From: FLORES, AIMEE
To: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Reel/Frame 065402/0261 →
Continuity (6)
Continuation
16627630
Provisional Application
62654095
· Apr 6, 2018
Provisional Application
62527775
· Jun 30, 2017
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