# US 10,766,865 B2 · PKM2 modulators and methods for their use

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- Number: US 10,766,865 B2
- Document ID: US10766865B2
- Status: Granted
- Kind: B2
- Application number: 16/584,912
- Filed: 2019-09-26
- Published: 2020-04-09
- Granted: 2020-09-08
- Earliest claimed: 2012-10-16
- Assignees: Sumitomo Dainippon Pharma Oncology, Inc.
- Applicants: Tolero Pharmaceuticals, Inc.
- Inventors: Koc-Kan Ho; Yong Xu; Michael David Saunders; Xiaohui Liu; Scott Albert Pearce; Kevin Bret Wright; Jason Marc Foulks; Kenneth Mark Parnell; Steven Brian Kanner; David Lee Vollmer; Jihua Liu
- Web page: https://patentgrep.com/patent/US10766865B2

## CPC

- C07D 231/14: with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- A61K 31/4155: non condensed and containing further heterocyclic rings
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 231/16: Halogen atoms or nitro radicals
- C07D 231/38: Nitrogen atoms (nitro radicals C07D231/16)
- C07D 401/12: linked by a chain containing hetero atoms as chain links
- C07D 401/14: containing three or more hetero rings
- C07D 403/12: linked by a chain containing hetero atoms as chain links
- C07D 403/14: containing three or more hetero rings
- C07D 405/12: linked by a chain containing hetero atoms as chain links
- C07D 405/14: containing three or more hetero rings
- C07D 409/12: linked by a chain containing hetero atoms as chain links
- C07D 409/14: containing three or more hetero rings
- C07D 413/12: linked by a chain containing hetero atoms as chain links
- C07D 417/12: linked by a chain containing hetero atoms as chain links
- C07D 417/14: containing three or more hetero rings
- C07F 9/65031: {having the nitrogen atoms in the positions 1 and 2}
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- 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
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)

## Abstract

Compounds having activity as PKM2 activators are disclosed. The compounds have the following structure (I): including stereoisomers, tautomers, pharmaceutically acceptable salts and prodrugs thereof, wherein R1, R2, R3, R4, R5 and R6 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

## Claims

### Claim 1

A method for increasing PKM2 activity in the provision of decreased tumorigenicity in a subject in need thereof, the method comprising:
administering an effective amount of a PKM2 activating compound in the form of a free-base or a pharmaceutically acceptable salt, or tautomer or prodrug thereof, to the subject, wherein said compound is:

### Claim 2 (depends on 1)

The method of claim 1, wherein the tumorigenicity is due to lung cancer, pancreatic cancer, skin cancer, colon cancer, breast cancer, kidney cancer, ovarian cancer, or a hematological malignancy.

### Claim 3 (depends on 1)

The method of claim 1, wherein the compound is:
or a pharmaceutically acceptable salt, tautomer, or prodrug thereof.

### Claim 4 (depends on 3)

The method of claim 3, wherein the tumorigenicity is due to lung cancer, pancreatic cancer, skin cancer, colon cancer, breast cancer, kidney cancer, ovarian cancer, or a hematological malignancy.

### Claim 5 (depends on 1)

The method of claim 1, wherein the compound is:
or a pharmaceutically acceptable salt, tautomer, or prodrug thereof.

### Claim 6 (depends on 5)

The method of claim 5, wherein the tumorigenicity is due to lung cancer, pancreatic cancer, skin cancer, colon cancer, breast cancer, kidney cancer, ovarian cancer, or a hematological malignancy.

### Claim 7 (depends on 1)

The method of claim 1, wherein the compound is:
or a pharmaceutically acceptable salt, tautomer, or prodrug thereof.

### Claim 8 (depends on 7)

The method of claim 7, wherein the tumorigenicity is due to lung cancer, pancreatic cancer, skin cancer, colon cancer, breast cancer, kidney cancer, ovarian cancer, or a hematological malignancy.

### Claim 9 (depends on 1)

The method of claim 1, wherein the compound is:
or a pharmaceutically acceptable salt, tautomer, or prodrug thereof.

### Claim 10 (depends on 9)

The method of claim 9, wherein the tumorigenicity is due to lung cancer, pancreatic cancer, skin cancer, colon cancer, breast cancer, kidney cancer, ovarian cancer, or a hematological malignancy.

### Claim 11 (depends on 1)

The method of claim 1, further comprising administering an effective amount of one or more chemotherapeutic agents to the subject.

### Claim 12 (depends on 3)

The method of claim 3, further comprising administering an effective amount of one or more chemotherapeutic agents to the subject.

### Claim 13 (depends on 5)

The method of claim 5, further comprising administering an effective amount of one or more chemotherapeutic agents to the subject.

### Claim 14 (depends on 7)

The method of claim 7, further comprising administering an effective amount of one or more chemotherapeutic agents to the subject.

### Claim 15 (depends on 9)

The method of claim 9, further comprising administering an effective amount of one or more chemotherapeutic agents to the subject.

### Claim 16 (depends on 1)

The method of claim 1, wherein the compound is:
in the form of a free-base.

### Claim 17 (depends on 1)

The method of claim 1, wherein the compound is:
in the form of a pharmaceutically acceptable salt.