Compounds for stem cell differentiation

• US 9,233,926 B2
• Filed: 03/23/2012
• Issued: 01/12/2016
• Est. Priority Date: 09/17/2008
• Status: Active Grant

• Current Assignee: ChemRegen Inc, Human Biomolecular Research Institute, Sanford Burnham Prebys Medical Discovery Institute
• Original Assignee: ChemRegen Inc, Human Biomolecular Research Institute, Sanford-Burnham Medical Research Institute (Sanford Burnham Prebys Medical Discovery Institute)
• Inventors: Mercola, Mark, Cashman, John, Lanier, Marion, Willems, Erik, Schade, Dennis
• Primary Examiner(s): REESE, HEIDI L
• Application Number:
  US13/428,647
• Publication Number:
  US 20130157947A1
• Time in Patent Office: 1,390 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61K 31/4709 Non-condensed quinolines and containing further heterocyclic rings
• CPC Class Codes: A61K 31/475 having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine vincamine A61K31/4375
• CPC Class Codes: A61K 38/1841 Transforming growth factor [TGF]
• CPC Class Codes: A61K 38/1875 Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
• CPC Class Codes: C07D 215/20 Oxygen atoms
• CPC Class Codes: C07D 215/54 attached in position 3
• CPC Class Codes: C07D 401/10 linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C12N 5/0618 Cells of the nervous system
• CPC Class Codes: C12N 5/0652 Cells of skeletal and connective tissues; Mesenchyme
• CPC Class Codes: C12N 5/0655 Chondrocytes; Cartilage
• CPC Class Codes: C12N 5/0657 Cardiomyocytes; Heart cells
• CPC Class Codes: C12N 5/067 Hepatocytes
• CPC Class Codes: C12N 5/0676 Pancreatic cells

Abstract

Small molecule compounds and methods for stem cell differentiation are provided herein. An example of a class of compounds that may be used to practice the methods disclosed herein is represented by enantiomerically pure isomers of compounds of Formula I:

or a chirally pure stereoisomer, pharmaceutically acceptable salt, or solvate thereof, wherein R¹, R², R³, R⁴, R⁵, R^5′, R⁶, R^6′, R⁷, R^7′ are as described herein.

Claims

1. A compound selected from the group consisting of:

compounds having structural Formula (I);

3. The compound of claim 1, wherein the pharmaceutically acceptable salt is the salt of 1-hydroxy-2-naphthoic acid, 2,2-dichloroacetic acid, 2-hydroxyethanesulfonic acid, 2-oxoglutaric acid, 4-acetamidobenzoic acid, 4-aminosalicylic acid, acetic acid, adipic acid, ascorbic acid (L), aspartic acid (L), benzenesulfonic acid, benzoic acid, camphoric acid (+), camphor-10-sulfonic acid (+), capric acid (decanoic acid), caproic acid (hexanoic acid), caprylic acid (octanoic acid), carbonic acid, cinnamic acid, citric acid, cyclamic acid, dodecylsulfuric acid, ethane-1,2-disulfonic acid, ethanesulfonic acid, formic acid, fumaric acid, galactaric acid, gentisic acid, glucoheptonic acid (D), gluconic acid (D), glucuronic acid (D), glutamic acid, glutaric acid, glycerophosphoric acid, glycolic acid, hippuric acid, hydrobromic acid, hydrochloric acid, isobutyric acid, lactic acid (DL), lactobionic acid, lauric acid, maleic acid, malic acid (−

L), malonic acid, mandelic acid (DL), methanesulfonic acid, naphthalene-1,5-disulfonic acid, naphthalene-2-sulfonic acid, nicotinic acid, nitric acid, oleic acid, oxalic acid, palmitic acid, pamoic acid, phosphoric acid, proprionic acid, pyroglutamic acid (−

L), salicylic acid, sebacic acid, stearic acid, succinic acid, sulfuric acid, tartaric acid (+L), thiocyanic acid, toluenesulfonic acid (p), or undecylenic acid.

4. The compound of claim 1, wherein the compound has structural Formula (I).

5. The compound of claim 4, wherein R¹⁴ is hydrogen.

6. The compound of claim 4, wherein R¹⁵ is ethyl.

7. The compound of claim 4, wherein R¹⁶ is methyl.

8. The compound of claim 1, wherein the compound has structural Formula (II).

9. The compound of claim 8, wherein R¹⁹ is phenyl.

10. The compound of claim 9, wherein R²³ is perhaloalkyl.

11. The compound of claim 1, wherein R¹⁹ is hydrogen.

12. The compound of claim 11, wherein R²³ is alkyl.

2. A compound:

selected from the group consisting of