Hair follicle stem cell activation and hair growth

Patent metadata

Field	Value
Publication number	US-10828289-B2
Application number	US-201716327966-A
Country	US
Kind code	B2
Filing date	Aug 25, 2017
Priority date	Aug 26, 2016
Publication date	Nov 10, 2020
Grant date	Nov 10, 2020

Abstract

There are provided, inter alia, methods and compounds and method for inducing hair growth in a subject in need thereof.

First claim

What is claimed is:

1. A method for inducing hair growth or inducing hair regeneration in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of formula (III):

wherein:
A is CH or N;
B is CH or N; and
R 10 is halogen, hydrogen, —CX 10.1 3 , —CHX 10.1 2 , —CH 2 X 10.1 , —CN, —SO n1 R 10A , —SO v1 NR 10B R 10C , —NHNR 10B R 10C , —ONR 10B R 10C , —NHC(O)NHNR 10B R 10C , —NHC(O)NR 10B R 10C , —N(O) m1 , —NR 10B R 10C , —C(O)R 10D , —C(O)OR 10D , —C(O)NR 10B R 10C , —OR 10A , —NR 10B SO 2 R 10A , —NR 10B C(O)R 10D , —NR 10B C(O)OR 10D , —NR 10B OR 10D , —OCX 10.1 3 , —OCHX 10.1 2 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
n1 is an integer from 0 to 4;
m1 is 1 or 2;
v1 is 1 or 2;
R 10A , R 10B , R 10C , and R 10D are independently hydrogen, halogen, —CF 3 , —CCl 3 , —CBr 3 , —CI 3 , —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)—OH, —NHOH, —OCF 3 , —OCCl 3 , —OCBr 3 , —OCI 3 , —OCHF 2 , —OCHCl 2 , —OCHBr 2 , —OCHI 2 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 10B and R 10C substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl; and
X 10.1 is independently —Cl, —Br, —I or —F.

2. The method of claim 1 , wherein R 10 is halogen.

3. The method of claim 1 , wherein R 10 is fluorine, chlorine, or iodine.

4. The method of claim 1 , wherein the compound of formula (III) is:

5. The method of claim 1 , wherein the compound of formula (III) is:

6. A method for activating a quiescent hair follicle stem cell in a subject in need thereof, the method comprising contacting a quiescent hair follicle stem cell with an effective amount of a compound of formula (III):

wherein:
A is CH or N;
B is CH or N; and
R 10 is halogen, hydrogen, —CX 10.1 3 , —CHX 10.1 2 , —CH 2 X 10.1 , —CN, —SO n1 R 10A , —SO v1 NR 10B R 10C , —NHNR 10B R 10C , —ONR 10B R 10C , —NHC(O)NHNR 10B R 10C , —NHC(O)NR 10B R 10C , —N(O) m1 , —NR 10B R 10C , —C(O)R 10D , —C(O)OR 10D , —C(O)NR 10B R 10C , —OR 10A , —NR 10B SO 2 R 10A , —NR 10B C(O)R 10D , —NR 10B C(O)OR 10D , —NR 10B OR 10D , —OCX 10.1 3 , —OCHX 10.1 2 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
n1 is an integer from 0 to 4;
m1 is 1 or 2;
v1 is 1 or 2;
R 10A , R 10B , R 10C , and R 10D are independently hydrogen, halogen, —CF 3 , —CCl 3 , —CBr 3 , —CI 3 , —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)—OH, —NHOH, —OCF 3 , —OCCl 3 , —OCBr 3 , —OCI 3 , —OCHF 2 , —OCHCl 2 , —OCHBr 2 , —OCHI 2 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 10B and R 10C substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl; and
X 10.1 is independently —Cl, —Br, —I or —F.

7. The method of claim 6 , wherein the quiescent hair follicle stem cell is a human hair follicle stem cell.

8. The method of claim 6 , wherein the subject is a human subject.

9. The method of claim 6 , wherein R 10 is halogen.

10. The method of claim 6 , wherein R 10 is fluorine, chlorine, or iodine.

11. The method of claim 6 , wherein the compound of formula (III) is:

12. The method of claim 6 , wherein the compound of formula (III) is:

13. A method for inducing glycolysis in a hair follicle stem cell or activating lactate dehydrogenase in a hair follicle stem cell, the method comprising contacting a hair follicle stem cell with an effective amount of a compound of formula (III):

wherein:
A is CH or N;
B is CH or N; and
R 10 is halogen, hydrogen, —CX 10.1 3 , —CHX 10.1 2 , —CH 2 X 10.1 , —CN, —SO n1 R 10A , —SO v1 NR 10B R 10C , —NHNR 10B R 10C , —ONR 10B R 10C , —NHC(O)NHNR 10B R 10C , —NHC(O)NR 10B R 10C , —N(O) m1 , —NR 10B R 10C , —C(O)R 10D , —C(O)OR 10D , —C(O)NR 10B R 10C , —OR 10A , —NR 10B SO 2 R 10A , —NR 10B C(O)R 10D , —NR 10B C(O)OR 10D , —NR 10B OR 10D , —OCX 10.1 3 , —OCHX 10.1 2 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
n1 is an integer from 0 to 4;
m1 is 1 or 2;
v1 is 1 or 2;
R 10A , R 10B , R 10C , and R 10D are independently hydrogen, halogen, —CF 3 , —CCl 3 , —CBr 3 , —CI 3 , —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)—OH, —NHOH, —OCF 3 , —OCCl 3 , —OCBr 3 , —OCI 3 , —OCHF 2 , —OCHCl 2 , —OCHBr 2 , —OCHI 2 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; R 10B and R 10C substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl; and
X 10.1 is independently —Cl, —Br, —I or —F.

14. The method of claim 13 , wherein the hair follicle stem cell is a quiescent hair follicle stem cell.

15. The method of claim 13 , wherein a level of a glycolytic metabolite in the hair follicle stem cell is increased relative to the absence of contacting the hair follicle stem cell with the compound of formula (III).

16. The method of claim 15 , wherein the glycolytic metabolite is glucose, fructose-6-phosphate, fructose-bisphosphate, dihydroxyacetone phosphate, 3-phosphoglycerate, lactate, or a combination of two or more thereof.

17. The method of claim 13 , wherein R 10 is halogen.

18. The method of claim 13 , wherein R 10 is fluorine, chlorine, or iodine.

19. The method of claim

Assignees

• Univ California

Inventors

• Lowry William

Classifications

• A61K8/98

  of animal origin · CPC title

• A61K8/4953

  containing pyrimidine ring derivatives, e.g. minoxidil · CPC title

• A61Q7/00

  Preparations for affecting hair growth · CPC title

• A61K8/49

  containing heterocyclic compounds · CPC title

• A61K31/426 Primary

  1,3-Thiazoles · CPC title