Acyl-CoA synthetase 4 (ACSL4) inhibitory compound

Patent metadata

Field	Value
Publication number	US-12280059-B2
Application number	US-202017433174-A
Country	US
Kind code	B2
Filing date	Feb 20, 2020
Priority date	Feb 21, 2019
Publication date	Apr 22, 2025
Grant date	Apr 22, 2025

Abstract

A new compound of formula A for the treatment of aggressive and/or resistant tumors expressing acyl-CoA synthetase 4 (ACSL4) and/or depending on steroids action. More particularly, the compound of the present invention inhibits tumor growth in ACSL4-expressing breast and prostate cancers, inhibits steroid synthesis and sensitizes cells towards chemotherapeutic and hormone therapy agents. Pharmaceutical compositions comprising the ACSL4-inhibitory compound of the invention, pharmaceutical combinations thereof with other anticancer agents and use in therapy.

First claim

The invention claimed is:

1. A compound (N-(4-(3-(5-methylfuran-2-yl)-1-phenyl-1H-pyrazol-4-yl)-3,4-dihydrobenzo[4,5]imidazo[1,2-α][1,3,5]triazin-2-yl)acetamide) of formula A,

an enantiomer, solvate, or pharmaceutically acceptable salt thereof.

2. A process for preparing the compound of formula A according to claim 1 , comprising reacting 4-(3-(5-methylfuran-2-yl)-1-phenyl-1H-pyrazol-4-yl)-3,4-dihydrobenzo [4,5]imidazo[1,2-a][1,3,5]triazin-2-amine with acetic anhydride.

3. The process according to claim 2 , comprising reacting 4-(3-(5-methylfuran-2-yl)-1-phenyl-1H-pyrazol-4-yl)-3,4-dihydrobenzo[4,5]imidazo[1,2-α][1,3,5]triazin-2-amine (formula B) with acetic anhydride, according to the following reaction:

4. A method for treating a patient having prostate cancer, breast cancer or triple negative breast cancer (TNBC), comprising administering to the patient a compound of formula A

or a compound of formula B

5. The method according to claim 4 , comprising administering the compound of formula A or the compound of formula B in combination with a chemotherapeutic agent.

6. The method according to claim 5 , wherein the chemotherapeutic agent is selected from doxorubicin, paclitaxel and cisplatin.

7. The method according to claim 4 , comprising administering the compound of formula A or the compound of formula B in combination with an estrogen receptor (ER) inhibitor.

8. The method according to claim 7 , wherein the ER inhibitor is selected from the group consisting of tamoxifen, bazedoxifene, lasofoxifene, ormeloxifene, raloxifene, clomifene, 4-OH-tamoxifen, toremifene, afimoxifen, endoxifen, idoxifen, droloxifen, N-demethyl-droloxifen, cis-tamoxifen, desethyl-tamoxifen, N-desmethyl-tamoxifen, tamoxifen citrate, dihydro-tamoxifen, iodo-tamoxifen, 4-chlorotamoxifen, 4-methyl-tamoxifen, 4-fluoro-tamoxifen, 2-methyl-4-hydroxy-tamoxifen, deamino-hydroxy-tamoxifen, 4-hydroxy-deamino-hydroxy-tamoxifen and 4-hydroxy-N-demethyl-tamoxifen.

Assignees

• Consejo Nacional De Investigaciones Cientificas Y Tecn Conicet
• Univ Nacional De Quilmes
• Univ Buenos Aires

Inventors

• Podestá Ernesto J
• Maloberti Paula M
• Orlando Ulises D
• Castillo Ana F
• Solano Angela R
• Lorenzano Menna Pablo
• Gomez Daniel E
• Szajnman Sergio H
• Prada Jessica G
• Rodriguez Juan B

Classifications

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• A61K31/704

  attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)} · CPC title

• A61K31/337

  having four-membered rings, e.g. taxol · CPC title

• A61K31/138

  Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine (atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377) · CPC title

• A61K33/243

  Platinum; Compounds thereof · CPC title