Macrocyclic compounds and methods of treatment

Patent metadata

Field	Value
Publication number	US-2024002396-A1
Application number	US-202118030747-A
Country	US
Kind code	A1
Filing date	Oct 6, 2021
Priority date	Oct 7, 2020
Publication date	Jan 4, 2024
Grant date	—

Abstract

The instant invention describes macrocyclic compounds having antiproliferation activity, and methods of treating disorders such as cancer, tumors and cell proliferation related disorders.

First claim

1 . A compound according to Formula I:

or pharmaceutically acceptable salt thereof, wherein;
R is H or OH.

2 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R is H.

3 . The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R is OH.

4 . A pharmaceutical composition comprising the compound of claim 1 , or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

5 . The pharmaceutical composition of claim 4 further comprising an additional therapeutic agent.

6 . The pharmaceutical composition of claim 5 , wherein the additional therapeutic agent is an anti-cancer agent, a chemotherapeutic agent, an anti-angiogenesis agent, a cytotoxic agent, or an anti-proliferation agent.

7 . A kit comprising an effective amount of a compound of claim 1 , in unit dosage form, together with instructions for administering the compound to a subject suffering from or susceptible to a cell proliferation disorder.

8 . A method of modulating the activity of cell proliferation in a subject, comprising administering to the subject the compound of claim 1 or pharmaceutically acceptable salt thereof.

9 . The method of claim 8 , wherein the cell is a cancer cell or a tumor cell.

10 . (canceled)

11 . The method of claim 8 , wherein the modulation is inhibition.

12 . A method of treating a subject suffering from or susceptible to a cell proliferation related disorder or disease, comprising administering to the subject an effective amount of the compound of claim 1 or pharmaceutically acceptable salt thereof.

13 . (canceled)

14 . The method of claim 12 , wherein the disorder or disease is cancer or a solid tumor.

15 - 16 . (canceled)

17 . The method of claim 12 , wherein the effective amount ranges from:
(a) about 0.005 μg/kg to about 200 mg/kg; (b) about 0.1 mg/kg to about 200 mg/kg; (c) about 10 mg/kg to 100 mg/kg; or (d) about 1.0 pM to about 500 μM.

18 - 20 . (canceled)

21 . The method of claim 12 , wherein the compound, or pharmaceutically acceptable salt thereof, is administered intravenously, intramuscularly, subcutaneously, intracerebroventricularly, orally, or topically.

22 . The method of claim 12 , wherein the compound, or pharmaceutically acceptable salt thereof, is administered alone or in combination with one or more other therapeutics.

23 . The method of claim 22 , wherein the one or more other therapeutics is selected from the group consisting of an anti-cancer agent, a chemotherapeutic agent, an anti-angiogenesis agent, a cytotoxic agent, and an anti-proliferation agent.

24 . A method of treating cancer or tumors, comprising administering to said subject in need thereof, an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

25 - 26 . (canceled)

27 . The method of claim 26 , further comprising further comprising administering to said subject an additional therapeutic agent.

28 . The method of claim 27 , wherein the additional therapeutic agent is an anti-cancer agent, a chemotherapeutic agent, an anti-angiogenesis agent, a cytotoxic agent, an anti-proliferation agent, or a tubulin-interactive anti-cancer agent.

29 . (canceled)

30 . The method of claim 14 , wherein the cancer is colon cancer, breast cancer, bone cancer, brain cancer, neuroblastoma, osteosarcoma, or colon adenocarcinoma.

Assignees

• Univ Florida
• Smithsonian Inst

Inventors

• Luesch Hendrik
• Paul Valerie J
• Matthew Susan
• Chen Qi-Yin
• Ratnayake Ranjala

Classifications

• C07D498/04 Primary

  Ortho-condensed systems · CPC title

• A61P35/00

  Antineoplastic agents · CPC title