# US 10,865,384 B2 · 2,4,5-tri-substituted azole-based casein kinase 1 inhibitors as inducers for cardiomyogenesis

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- Number: US 10,865,384 B2
- Document ID: US10865384B2
- Status: Granted
- Kind: B2
- Application number: 15/117,127
- Filed: 2015-02-06
- Published: 2017-06-15
- Granted: 2020-12-15
- Earliest claimed: 2014-02-07
- Assignees: Agency for Science, Technology and Research; National University of Singapore
- Applicants: Agency for Science, Technology and Research; National University of Singapore
- Inventors: Filip Laco; Joo Leng Low; Steve Oh; Christina Li Lin Chai; Qixing Zhong
- Web page: https://patentgrep.com/patent/US10865384B2

## CPC

- C12N 5/0657: {Cardiomyocytes; Heart cells}
- A61K 31/4178: not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
- A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465)
- A61K 31/506: not condensed and containing further heterocyclic rings
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/02: Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- C07D 405/04: directly linked by a ring-member-to-ring-member bond
- C07D 405/14: containing three or more hetero rings
- C07D 413/04: directly linked by a ring-member-to-ring-member bond
- C12N 2501/727: Kinases (EC 2.7.)
- C12N 2501/999: Small molecules not provided for elsewhere
- C12N 2506/02: from embryonic cells
- C12N 2506/45: from artificially induced pluripotent stem cells
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

This invention relates to a method for inducing or enhancing the differentiation of pluripotent stem cells into cardiomyocyte via casein kinase 1 inhibition said method comprising culturing the stem cells in the presence of a medium comprising a casein kinase 1 inhibitor of the formula (I) or (II) or a stereoisomer, tautomer, or a salt thereof wherein R1, R2 and R3 independently from another represent hydrogen, optionally substituted alkyl, alkenyl, alkynyl, heterocyclyl, heteroaryl or aryl; X represents NR4, O or S; and R4 represents hydrogen, optionally substituted alkyl, alkenyl, alkynyl, heterocyclyl, heteroaryl or aryl. The method can be used in the late phase of stem cell differentiation and in the compounds of formula (I) or (II) in combination with other small molecules can lead to especially high differentiation of stem cells into cardiomyocytes. The invention further relates to novel compounds which can be used in the method of the invention and kits for stem cell differentiation.

## Claims

### Claim 1

A compound selected from the following compounds, or a tautomer, or a salt thereof:

### Claim 2 (depends on 1)

The compound according to claim 1, wherein the compound is:
or a tautomer or a salt thereof.

### Claim 3

A compound or a tautomer or a salt thereof, wherein the compound is: