Compounds and compositions for the treatment of tumors

Patent metadata

Field	Value
Publication number	US-12459914-B2
Application number	US-202017783729-A
Country	US
Kind code	B2
Filing date	Dec 11, 2020
Priority date	Dec 11, 2019
Publication date	Nov 4, 2025
Grant date	Nov 4, 2025

Abstract

The present invention relates to compounds of Formula (Ia) or pharmaceutically acceptable salts, hydrates, solvates, clathrates, polymorphs, stereoisomers thereof. It further discloses a pharmaceutical composition comprising compounds of Formula (Ia) and the use of compounds of Formula (Ib), in particular for the use in the treatment of diseases or disorders wherein disrupting Rad51-BRCA2 interaction is beneficial.

First claim

The invention claimed is:

1. A compound of formula (Ia):

wherein
R 1 is halogen;
R 2 is selected from the group consisting of hydrogen and COOH;
n is 1;
Y is C 1-4 alkyl;
A is phenyl;
B is selected from the group consisting of

R 5 is hydrogen, halogen, linear or branched C 1-4 alkyl, halo-C 1-4 alkyl, O—C 1-4 alkyl;
R 6 is selected from the group consisting of H and C 1-4 alkyl;
m is 1 or 2; and
W is selected from the group consisting of O and NH;
or compounds of formula (Ia):

wherein
R 1 is halogen;
R 2 is selected from the group consisting of hydrogen and COOH;
n is 0;
Y is selected from the group consisting of C 1-4 alkyl;
A is morpholino;
B is

R 5 is hydrogen, halogen, linear or branched C 1-4 alkyl, halo-C 1-4 alkyl, O—C 1-4 alkyl;
R 6 is selected from the group consisting of H and C 1-4 alkyl;
m is 1 or 2; and
W is selected from the group consisting of O and NH,
or their pharmaceutically acceptable salts or solvates or isomers thereof.

2. The compound according to claim 1 selected from the group consisting of:

d.50
4-[5-(4-benzyl-6-chloro-2-oxo-1H-quinolin-3-yl)-3-(4-fluorophenyl)-3,4-

dihydropyrazol-2-yl]-4-oxo-butanoic acid

d.51
3-[2-acetyl-3-(4-fluorophenyl)-3,4-dihydropyrazol-5-yl]-4-benzyl-6-chloro-

1H-quinolin-2-one

d.52
3-[2-acetyl-3-(4-methoxyphenyl)-3,4-dihydropyrazol-5-yl]-4-benzyl-6-

chloro-1H-quinolin-2-one

d.53
4-benzyl-6-chloro-3-[3-(4-methoxyphenyl)-2-propanoyl-3,4-dihydropyrazol-

5-yl]-1H-quinolin-2-one

d.54
4-benzyl-6-chloro-3-[3-(4-fluorophenyl)-2-propanoyl-3,4-dihydropyrazol-5-

yl]-1H-quinolin-2-one

d.55
4-[5-(4-benzyl-6-chloro-2-oxo-1H-quinolin-3-yl)-3-(4-chlorophenyl)-3,4-

dihydropyrazol-2-yl]-4-oxo-butanoic acid

d.56
3-[2-acetyl-3-(4-chlorophenyl)-3,4-dihydropyrazol-5-yl]-4-benzyl-6-chloro-

1H-quinolin-2-one

d.57
4-benzyl-6-chloro-3-[3-(4-chlorophenyl)-2-propanoyl-3,4-dihydropyrazol-5-

yl]-1H-quinolin-2-one

d.58
4-[5-(4-benzyl-6-chloro-2-oxo-1H-quinolin-3-yl)-3-(4-bromophenyl)-3,4-

dihydropyrazol-2-yl]-4-oxo-butanoic acid

d.59
3-[2-acetyl-3-(4-bromophenyl)-3,4-dihydropyrazol-5-yl]-4-benzyl-6-chloro-

1H-quinolin-2-one

d.60
4-benzyl-3-[3-(4-bromophenyl)-2-propanoyl-3,4-dihydropyrazol-5-yl]-6-

chloro-1H-quinolin-2-one

d.61
4-[5-(4-benzyl-6-chloro-2-oxo-1H-quinolin-3-yl)-3-(4-methoxyphenyl)-3,4-

dihydropyrazol-2-yl]-4-oxo-butanoic acid

d.62
4-[5-(4-benzyl-6-chloro-2-oxo-1H-quinolin-3-yl)-3-[4-

(trifluoromethyl)phenyl]-3,4-dihydropyrazol-2-yl]-4-oxo-butanoic acid

d.63
3-[2-acetyl-3-[4-(trifluoromethyl)phenyl]-3,4-dihydropyrazol-5-yl]-4-

benzyl-6-chloro-1H-quinolin-2-one

d.64
4-[5-(4-benzyl-6-chloro-2-oxo-1H-quinolin-3-yl)-3-(4-tert-butylphenyl)-3,4-

dihydropyrazol-2-yl]-4-oxo-butanoic acid

d.65
3-[2-acetyl-3-(4-tert-butylphenyl)-3,4-dihydropyrazol-5-yl]-4-benzyl-6-

chloro-1H-quinolin-2-one

d.66
4-[5-(4-benzyl-6-chloro-2-oxo-1H-quinolin-3-yl)-3-(3-fluoro-4-methoxy-

phenyl)-3,4-dihydropyrazol-2-yl]-4-oxo-butanoic acid

d.67
4-[5-(4-benzyl-6-chloro-2-oxo-1H-quinolin-3-yl)-3-(2-furyl)-3,4-

dihydropyrazol-2-yl]-4-oxo-butanoic acid

d.68
3-[2-acetyl-3-(2-furyl)-3,4-dihydropyrazol-5-yl]-4-benzyl-6-chloro-1H-

quinolin-2-one

d.69
4-[5-(4-benzyl-6-chloro-2-oxo-1H-quinolin-3-yl)-3-(1-methylindol-5-yl)-

3,4-dihydropyrazol-2-yl]-4-oxo-butanoic acid

d.70
3-[2-acetyl-3-(1-methylindol-5-yl)-3,4-dihydropyrazol-5-yl]-4-benzyl-6-

chloro-1H-quinolin-2-one

d.71
4-[5-(4-benzyl-6-chloro-2-oxo-1H-quinolin-3-yl)-3-(1-ethylindol-5-yl)-3,4-

dihydropyrazol-2-yl]-4-oxo-butanoic acid

d.72
3-[2-acetyl-3-(1-ethylindol-5-yl)-3,4-dihydropyrazol-5-yl]-4-benzyl-6-

chloro-1H-quinolin-2-one

d.73
4-[5-(4-benzyl-6-chloro-2-oxo-1H-quinolin-3-yl)-3-(1-methylindazol-5-yl)-

3,4-dihydropyrazol-2-yl]-4-oxo-butanoic acid

d.74
3-[2-acetyl-3-(1-methylindazol-5-yl)-3,4-dihydropyrazol-5-yl]-4-benzyl-6-

chloro-1H-quinolin-2-one

d.75
4-[5-(4-benzyl-6-chloro-2-oxo-1H-quinolin-3-yl)-3-(2-methylindazol-5-yl)-

3,4-dihydropyrazol-2-yl]-4-oxo-butanoic acid

d.76
4-[5-(4-benzyl-6-chloro-2-oxo-1H-quinolin-3-yl)-3-(2-ethylindazol-5-yl)-

Assignees

• Fondazione St Italiano Tecnologia
• Tes Pharma S R L
• Alma Mater Studiorum—Universita di Bologna
• St Europeo Di Oncologia S R L

Inventors

• Cavalli Andrea
• Milano Domenico
• Manerba Marcella
• Bagnolini Greta
• Ortega Martinez Jose Antonio
• Roberti Marinella
• Stefano Giuseppina Di
• Pellicciari Roberto
• De Franco Francesca
• Minucci Saverio
• Pelicci Pier Giuseppe
• Previtali Viola

Classifications

• C07D401/14

  containing three or more hetero rings · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07D405/14

  containing three or more hetero rings · CPC title

• C07D401/04 Primary

  directly linked by a ring-member-to-ring-member bond · CPC title