IP Library Granted Patent US 49,338
Granted Patent E1
US 49,338 · App. 16/447,174 · Granted Dec 20, 2022

Phthalazinone derivatives and manufacturing process thereof

Inventors: Jae-Hoon Kang (Seoul, KR); Hong-Sub Lee (Gyeonggi-do, KR); Yoon-Suk Lee (Gyeonggi-do, KR); Joon-Tae Park (Gyeonggi-do, KR); Kyung-Mi An (Gyeonggi-do, KR); Jin-Ah Jeong (Seoul, KR); Kyung-Sun Kim (Gyeonggi-do, KR); Jeong-Geun Kim (Gyeonggi-do, KR); Chang-Hee Hong (Seoul, KR); Sun-Young Park (Gyeonggi-do, KR); Dong-Keun Song (Gyeonggi-do, KR); Yong-Don Yun (Gyeonggi-do, KR)
Assignee: IDIENCE CO., LTD.
C07D417/14C07D401/14C07D403/08C07D403/10C07D403/14
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Quick Facts
Patent No.
US 49,338
App. No.
16/447,174
Granted
Dec 20, 2022
Kind
E1
Abstract

The present invention relates to phthalazinone derivatives, including pharmaceutical compositions and for the preparation of phthalazinone derivatives. And more particularly the present invention provided a pharmaceutical composition of phthalazinone derivatives for inhibiting activity of the Poly(ADP-riboside) polymerase enzyme.

Claims (254)

1. A compound represented by Formula I, a racemic mixture thereof, an enantiomer thereof, a diastereoisomer thereof, or a pharmaceutically acceptable salt thereof,

In wherein in the present Formula I,

n is 1 or 2,

Wherein wherein, when the R is

m is 0, 1 or 2,

L is oxygen, methylene, carbonyl, CONHCH 2 , NR c1 CH 2 , NR c2 CO, NR c3 , CONR c4 or CH 2 NR c5 (especially, R c1 , wherein R c2 , R c3 , R c4 and R c5 is each independently oxygen, C 1-4 alkylamine, hydrogen, C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, or C 3-8 cycloalkyl,

R X is hydrogen, cyano, hydroxyl, trifluoromethyl, C 1-6 alkyl or C 3-8 cycloalkyl methyl, ethyl or cyclopropyl,

R Y is hydrogen, amide dimethylamide, cyano, hydroxyl, trifluoromethyl, halo, ester ethylester, C 1-4 alkylamine, C 1-6 alkyl, C 1-6 methoxyalkyl or C 2-6 alkynyl dimethylamine, methyl, methoxymethyl or propargyl,

Z is unsubstituted, C 1-6 alkyl, C 1-6 methoxyalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, C 3-8 cycloalkenyl, C 6-10 aromatic cycle or 3-8 membered heterocycle having 1-3 nitrogens,

wherein, when the R is

p and q is each independently from 1 to 3 1 or 2,

W is CR d1 R d2 or NR d3 (especially, wherein R d1 , R d2 and R d3 is each independently hydrogen, fluoro or C 1-6 alkyl) methyl,

wherein, when the R is

R 1 , R 2 and R 3 is each independently hydrogenor C 1-6 alkyl, methyl, or ethyl.

2. The compound according to claim 1 ,

wherein, L is methylene, carbonyl, CONHCH 2 , NR c1 CH 2 , NR c2 CO, NR c3 , CONR c4 or CH 2 NR c5 (especially, R c1 , R c2 , R c3 , R c4 and R c5 is each independently hydrogen, C 1-6 alkyl, C 2-6 alkynyl or C 3-8 cycloalkyl),

R X is hydrogen, cyano, hydroxyl, trifluoromethyl, methyl, ethyl or cyclopropyl,

R Y is hydrogen, dimethylamide, cyano, hydroxyl, trifluoromethyl, halo, ethylester, dimethylamine, methyl, methoxymethyl or propargyl,

Z is unsubstituted, C 1-6 alkyl, C 1-6 methoxyalkyl, C 2-6 alkynyl, C 3-8 cycloalkyl, C 6-10 aromatic cycle or 3-8 membered heterocycle having 1-3 nitrogens,

p and q is each independently 1 or 2,

W is CR d1 R d2 or NR d3 (especially R d1 , R d2 and R d3 is each independently hydrogen, fluoro or methyl),

R 1 , R 2 and R 3 is each independently hydrogen, methyl or ethyl.

3. The compound according to claim 1 ,

wherein, L is NR c1 CH 2 , CONR c4 or CH 2 NR c5 (especially, R c1 , R c4 and R c5 is each independently hydrogen, methyl, ethyl, propyl, propargyl or cyclopropyl),

Z is

4. The compound according to claim 1 ,

wherein, L is methylene or carbonyl,

Z is

5. The compound according to claim 1 ,

wherein, L is CONHCH 2 or NR c2 CO(especially, wherein R c2 is hydrogen, methyl, ethyl or propyl),

Z is

6. The compound according to claim 1 ,

wherein, the present R is

R is

7. The compound according to claim 1 ,

wherein, the compound represented by Formula I is selected from the group Consisting of the following compounds:

(R)-4-(3-(3-aminopyrrolidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

(S)-4-(3-(3-aminopyrrolidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(3-(3-aminoazetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

(R)-4-(4-fluoro-3-(3-hydroxypyrrolidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

(S)-4-(4-fluoro-3-(3-hydroxypyrrolidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-hydroxyazetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-(hydroxymethyl)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

(R)—N-(1-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)pyrrolidin-3-yl)cyclopropanecarboxamide;

N-(1-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)azetidin-3-yl)cyclopropanecarboxamide;

(S)—N-(1-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)pyrrolidin-3-yl)cyclopropanecarboxamide;

(R)—N-(1-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)pyrrolidin-3-yl)-N-methylcyclopropanecarboxamide;

N-(1-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)azetidin-3-yl)-N-methylcyclopropanecarboxamide;

(S)—N-(1-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)pyrrolidin-3-yl)-N-methylcyclopropanecarboxamide;

3-(1-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)azetidin-3-yl)-5,5-dimethylimidazolidine-2,4-dione;

(R)-3-(1-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)pyrrolidin-3-yl)imidazolidine-2,4-dione;

(R)-1-ethyl-3-(1-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)pyrrolidin-3-yl)imidazolidine-2,4-dione;

4-(4-fluoro-3-(3-(4-fluoropiperidine-1-carbonyl)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(3-(3-(3,3-difluoroazetidine-1-carbonyl)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(3-(3-(3,3-difluoropyrrolidine-1-carbonyl)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(3-(3-(3,3-difluoropyrrolidine-1-carbonyl)pyrrolidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

(R)—N-(cyclopropylmethyl)-1-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)pyrrolidine-3-carboxamide;

4-(4-fluoro-3-(3-(pyrrolidine-1-carbonyl)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

(R)-4-(3-(3-(3-(dimethylamino)pyrrolidine-1-carbonyl)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

(S)-4-(3-(3-(3-(dimethylamino)pyrrolidine-1-carbonyl)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(3-(3-(cyclobutylamino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(3-(3-(cyclopropylamino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(3-(3-(cyclopentylamino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(3-(3-(cyclohexylamino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

(R)-4-(3-(3-(cyclopropylamino)pyrrolidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

(R)-4-(3-(3-(cyclobutylamino)pyrrolidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

(R)-4-(3-(3-(cyclopentylamino)pyrrolidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-(isopropylamino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(3-(3-((cyclopropylmethyl)amino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(3-(3-(bis(cyclopropylmethyl)amino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-(isobutylamino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-((1-hydroxypropan-2-yl)amino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-(neopentylamino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(3-(3-((2,2-dimethylcyclopentyl)amino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

ethyl 2-((1-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)azetidin-3-yl)amino)cyclopent-1-enecarboxylate;

4-(4-fluoro-3-(3-(pentan-3-ylamino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-((3-methylbutan-2-yl)amino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(3-(3-((1-cyclopropylethyl)amino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(3-(3-(bicyclo[2.2.1]heptan-2-ylamino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(3-(3-(sec-butylamino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(3-(3-((dicyclopropylmethyl)amino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-((4-methylpentan-2-yl)amino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-((3-hydroxybutan-2-yl)amino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-(pentan-2-ylamino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-((1-(1-methyl cyclopropyl)ethyl)amino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-((3,3,3-trifluoro-2-methylpropyl)amino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(3-(3-(allylamino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-(isopentylamino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(3-(3-(butylamino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-((3-methylbut-2-en-1-yl)amino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(3-(3-((cyclopentylmethyl)amino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-((4,4,4-trifluorobutyl)amino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-(pentylamino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(3-(3-((2-cyclopropylethyl)amino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-(propylamino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-(methyl(pyridin-4-ylmethyl)amino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

(R)-4-(4-fluoro-3-(3-(methyl(pyridin-4-ylmethyl)amino)pyrrolidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

(S)-4-(4-fluoro-3-(3-(methyl(pyridin-4-ylmethyl)amino)pyrrolidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

(S)-4-(4-fluoro-3-(3-(methyl(pyridin-2-ylmethyl)amino)pyrrolidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

(R)-4-(4-fluoro-3-(3-(methyl(pyridin-2-ylmethyl)amino)pyrrolidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-(methyl(pyridin-2-ylmethyl)amino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-(methyl(pyridin-3-ylmethyl)amino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

(S)-4-(4-fluoro-3-(3-(methyl(pyridin-3-ylmethyl)amino)pyrrolidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

(R)-4-(4-fluoro-3-(3-(methyl(pyridin-3-ylmethyl)amino)pyrrolidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(3-(3-(cyclopropyl(methyl)amino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(3-(3-(cyclopropyl(ethyl)amino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(3-(3-(cyclobutyl(methyl)amino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(3-(3-(cyclopentyl(prop-2-yn-1-yl)amino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(3-(3-(3,3-difluoropyrrolidin-1-yl)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-(4-fluoropiperidin-1-yl)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(3-([1,3′-biazetidine]-1′-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-(pyrrolidin-1-yl)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-(piperidin-1-yl)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-(4-methylpiperazin-1-yl)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-(phenylamino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-((1-(trifluoromethyl)cyclopropyl)amino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-(prop-2-yn-1-ylamino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

(S)-4-(4-fluoro-3-(3-((1-methoxypropan-2-yl)amino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

(R)-4-(4-fluoro-3-(3-((1-methoxypropan-2-yl)amino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-((1-(hydroxymethyl)cyclopropyl)amino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-((1-methylcyclopropyl)amino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

(R)-4-(3-(3-((3,3-dimethylbutan-2-yl)amino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

(S)-4-(3-(3-((3,3-dimethylbutan-2-yl)amino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

(R)-4-(4-fluoro-3-(3-((3-methylbutan-2-yl)amino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

(S)-4-(4-fluoro-3-(3-((3-methylbutan-2-yl)amino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-((1-(methoxymethyl)cyclopropyl)amino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(3-(3-(but-3-yn-1-ylamino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-((2-methylallyl)amino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-((3-hydroxy-2,2-dimethylpropyl)amino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

1-(((1-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)azetidin-3-yl)amino)methyl)cyclopropanecarbonitrile;

4-(4-fluoro-3-(3-((2,2,2-trifluoroethyl)amino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

(R)-4-(4-fluoro-3-(3-(pyrrolidin-3-ylamino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

(S)-4-(4-fluoro-3-(3-(pyrrolidin-3-ylamino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

1-((1-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)azetidin-3-yl)amino)cyclopentanecarbonitrile;

1-((1-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)azetidin-3-yl)amino)cyclobutanecarbonitrile;

2-((1-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)azetidin-3-yl)amino)propanenitrile;

2-((1-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)azetidin-3-yl)amino)butanenitrile;

2-((1-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)azetidin-3-yl)amino)-3-methylbutanenitrile;

2-cyclopropyl-2-((1-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)azetidin-3-yl)amino)acetonitrile;

4-(4-fluoro-3-(3-((1-(trifluoromethyl)cyclobutyl)amino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

(S)-4-(4-fluoro-3-(3-(methyl(pyrimidin-2-yl)amino)pyrrolidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

(S)-4-(4-fluoro-3-(3-(methyl(pyrimidin-2-yl)amino)pyrrolidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-(methyl(pyrimidin-2-yl)amino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-(methyl(pyrimidin-2-yl)amino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-(pyrimidin-2-ylamino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

(S)-4-(4-fluoro-3-(3-(pyrimidin-2-ylamino)pyrrolidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

(S)-4-(3-(3-((6-chloropyridazin-3-yl)(methyl)amino)pyrrolidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

(S)-4-(3-(3-((6-chloropyridazin-3-yl)amino)pyrrolidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

(S)-4-(4-fluoro-3-(3-(methyl(pyridazin-3-yl)amino)pyrrolidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(3-(3-((6-chloropyridazin-3-yl)amino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(3-(3-((6-chloropyridazin-3-yl)(methyl)amino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(3-(3-(cyclobutyl(pyrimidin-2-yl)amino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-(pyridazin-3-ylamino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

(R)-4-(3-(3-((6-chloropyridazin-3-yl)amino)pyrrolidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

(R)-4-(3-(3-((6-chloropyridazin-3-yl)(methyl)amino)pyrrolidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

(R)-4-(4-fluoro-3-(3-(pyrimidin-2-ylamino)pyrrolidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

(R)-4-(3-(3-(methyl(pyrimidin-2-yl)amino)pyrrolidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

(R)-4-(4-fluoro-3-(3-(pyridazin-3-ylamino)pyrrolidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

(R)-4-(4-fluoro-3-(3-(methyl(pyridazin-3-yl)amino)pyrrolidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

(R)-4-(4-fluoro-3-(3-(thiazol-2-ylamino)pyrrolidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

(R)-4-(3-(3-((5-ethynylpyrimidin-2-yl)amino)pyrrolidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

(R)-2-((1-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)pyrrolidin-3-yl)amino)pyrimidine-5-carbonitrile;

(R)-2-((1-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)pyrrolidin-3-yl)amino)nicotinonitrile;

(R)-4-(4-fluoro-3-(3-(pyridin-2-ylamino)pyrrolidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

(R)-2-((1-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)pyrrolidin-3-yl)amino)-N,N-dimethylnicotinamide;

(R)-4-(3-(3-((5-bromopyrimidin-2-yl)amino)pyrrolidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

(R)-4-(4-fluoro-3-(3-((5-(trifluoromethyl)pyridin-2-yl)amino)pyrrolidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

(R)-4-(4-fluoro-3-(3-((4-(trifluoromethyl)pyridin-2-yl)amino)pyrrolidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(3-(3-(benzylamino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-((3,3,3-trifluoropropyl)amino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

(R)-4-(3-(3-(azetidin-1-yl)pyrrolidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

(R)-4-(3-([1,3′-bipyrrolidine]-1′-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

(R)-4-(4-fluoro-3-(3-(piperidin-1-yl)pyrrolidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

(R)-4-(4-fluoro-3-(3-(p-tolylamino)pyrrolidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

(R)-4-(4-fluoro-3-(3-(phenylamino)pyrrolidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-(pyrrolidin-1-ylmethyl)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-(piperidin-1-ylmethyl)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(3-(3-(azetidin-1-ylmethyl)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(3-(3-((cyclopropylamino)methyl)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-((isopropylamino)methyl)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(3-(3-(((cyclopropylmethyl)amino)methyl)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-((isobutylamino)methyl)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(3-(3-((tert-butylamino)methyl)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(3-(3-((cyclobutylamino)methyl)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-((prop-2-yn-1-ylamino)methyl)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one; 4-(4-fluoro-3-(3-((phenylamino)methyl)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

1-((((1-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)azetidin-3-yl)methyl)amino)methyl)cyclopropanecarbonitrile;

1-(((1-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)azetidin-3-yl)methyl)amino)cyclopropanecarbonitrile;

4-(3-(3-((cyclopropyl(prop-2-yn-1-yl)amino)methyl)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(3-(3-((cyclopropyl(methyl)amino)methyl)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(3-(3-((cyclopropyl(ethyl)amino)methyl)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(3-(3-(cyclobutylamino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one hydrochloride;

4-(3-(3-(cyclopropylamino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one hydrochloride;

4-(3-(3-(cyclopentylamino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one hydrochloride;

4-(4-fluoro-3-(3-(isopropylamino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one hydrochloride;

4-(3-(3-((cyclopropylmethyl)amino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one hydrochloride;

4-(4-fluoro-3-(3-(isobutylamino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one hydrochloride;

4-(4-fluoro-3-(3-((1-hydroxypropan-2-yl)amino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one hydrochloride;

4-(3-(3-(butylamino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one hydrochloride;

4-(3-([1,3′-biazetidine]-1′-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one hydrochloride;

(R)-4-(4-fluoro-3-(3-((1-methoxypropan-2-yl)amino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one hydrochloride;

1-((1-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)azetidin-3-yl)amino)cyclobutanecarbonitrile hydrochloride;

(R)-4-(3-(3-(azetidin-1-yl)pyrrolidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one hydrochloride;

4-(4-fluoro-3-(3-(pyrrolidin-1-ylmethyl)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one hydrochloride;

4-(4-fluoro-3-(3-(piperidin-1-ylmethyl)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one hydrochloride;

4-(3-(3-(azetidin-1-ylmethyl)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one hydrochloride;

4-(3-(3-((cyclopropylamino)methyl)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one hydrochloride;

4-(4-fluoro-3-(3-((isopropylamino)methyl)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one hydrochloride;

4-(3-(3-(((cyclopropylmethyl)amino)methyl)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one hydrochloride;

4-(4-fluoro-3-(3-((isobutylamino)methyl)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one hydrochloride;

4-(3-(3-((cyclobutylamino)methyl)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one hydrochloride; and

4-(4-fluoro-3-(3-((prop-2-yn-1-ylamino)methyl)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one hydrochloride.

8. A compound, a racemic mixture thereof, an enantiomer thereof, a diastereoisomer thereof, or a pharmaceutically acceptable salt thereof, selected from the group consisting of the following:

4-(3-(3-(cyclopentylamino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

(R)-4-(3-(3-(cyclopropylamino)pyrrolidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

(R)-4-(3-(3-(cyclopentylamino)pyrrolidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-(isopropylamino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(3-(3-((cyclopropylmethyl)amino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-(isobutylamino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-((-1-(trifluoromethyl)cyclopropyl)amino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(3-(3-((cyclopropylamino)methyl)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one;

4-(4-fluoro-3-(3-((isopropylamino)methyl)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one;

4-(3-(3-(((cyclopropylmethyl)amino)methyl)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one; and

4-(3-(3-((cyclobutylamino)methyl)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one.

9. The compound according to claim 8, wherein the compound is 4-(3-(3-(cyclopentylamino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one, or a pharmaceutically acceptable salt thereof.

10. The compound according to claim 8, wherein the compound is (R)-4-(3-(3-(cyclopropylamino)pyrrolidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one, or a pharmaceutically acceptable salt thereof.

11. The compound according to claim 8, wherein the compound is (R)-4-(3-(3-(cyclopentylamino)pyrrolidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one, or a pharmaceutically acceptable salt thereof.

12. The compound according to claim 8, wherein the compound is 4-(4-fluoro-3-(3-(isopropylamino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one, or a pharmaceutically acceptable salt thereof.

13. The compound according to claim 8, wherein the compound is 4-(3-(3-((cyclopropylmethyl)amino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one, or a pharmaceutically acceptable salt thereof.

14. The compound according to claim 8, wherein the compound is 4-(4-fluoro-3-(3-(isobutylamino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one, or a pharmaceutically acceptable salt thereof.

15. The compound according to claim 8, wherein the compound is 4-(4-fluoro-3-(3-((1-(trifluoromethyl)cyclopropyl)amino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one, or a pharmaceutically acceptable salt thereof.

16. The compound according to claim 8, wherein the compound is 4-(3-(3-((cyclopropylamino)methyl)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one, or a pharmaceutically acceptable salt thereof.

17. The compound according to claim 8, wherein the compound is 4-(4-fluoro-3-(3-((isopropylamino)methyl)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one, or a pharmaceutically acceptable salt thereof.

18. The compound according to claim 8, wherein the compound is 4-(3-(3-(((cyclopropylmethyl)amino)methyl)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one, or a pharmaceutically acceptable salt thereof.

19. The compound according to claim 8, wherein the compound is 4-(3-(3-((cyclobutylamino)methyl)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one, or a pharmaceutically acceptable salt thereof.

20. The compound according to claim 8, wherein the compound is 4-(3-(3-(cyclopentylamino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one hydrochloride.

21. The compound according to claim 8, wherein the compound is 4-(4-fluoro-3-(3-(isopropylamino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one hydrochloride.

22. The compound according to claim 8, wherein the compound is 4-(3-(3-((cyclopropylmethyl)amino)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one hydrochloride.

23. The compound according to claim 8, wherein the compound is 4-(4-fluoro-3-(3-(isobutylamino)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one hydrochloride.

24. The compound according to claim 8, wherein the compound is 4-(3-(3-((cyclopropylamino)methyl)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one hydrochloride.

25. The compound according to claim 8, wherein the compound is 4-(4-fluoro-3-(3-((isopropylamino)methyl)azetidine-1-carbonyl)benzyl)phthalazin-1(2H)-one hydrochloride.

26. The compound according to claim 8, wherein the compound is 4-(3-(3-(((cyclopropylmethyl)amino)methyl)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one hydrochloride.

27. The compound according to claim 8, wherein the compound is 4-(3-(3-((cyclobutylamino)methyl)azetidine-1-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one hydrochloride.

28. A pharmaceutical composition comprising the compound of claim 8 and a pharmaceutically acceptable excipient.

29. A pharmaceutical composition comprising the compound of claim 16 and a pharmaceutically acceptable excipient.

30. A pharmaceutical composition comprising the compound of claim 24 and a pharmaceutically acceptable excipient.

31. A method of inhibiting growth of a tumor associated with cancer in a subject, comprising administering a therapeutically effective amount of the pharmaceutical composition of claim 28 to the subject.

32. The method according to claim 31, wherein the cancer is caused by a defect of BRCA1, BRCA2, and ERG fusion gene.

33. The method according to claim 32, wherein the cancer is selected from the group consisting of breast cancer, ovarian cancer, pancreatic cancer, gastric cancer, lung cancer, colorectal cancer, brain tumor, prostate cancer and Ewings sarcoma.

34. A method of inhibiting growth of a tumor associated with cancer in a subject, comprising administering a therapeutically effective amount of the pharmaceutical composition of claim 29 to the subject.

35. The method according to claim 34, wherein the cancer is caused by a defect of BRCA1, BRCA2, and ERG fusion gene.

36. The method according to claim 35, wherein the cancer is selected from the group consisting of breast cancer, ovarian cancer, pancreatic cancer, gastric cancer, lung cancer, colorectal cancer, brain tumor, prostate cancer and Ewings sarcoma.

37. A method of inhibiting growth of a tumor associated with cancer in a subject, comprising administering a therapeutically effective amount of the pharmaceutical composition of claim 30 to the subject.

38. The method according to claim 37, wherein the cancer is caused by a defect of BRCA1, BRCA2, and ERG fusion gene.

39. The method according to claim 38, wherein the cancer is selected from the group consisting of breast cancer, ovarian cancer, pancreatic cancer, gastric cancer, lung cancer, colorectal cancer, brain tumor, prostate cancer and Ewings sarcoma.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 28, 2020
From: IL DONG PHARMACEUTICAL CO., LTD.
To: IDIENCE CO., LTD.
Reel/Frame 051648/0567 →
DEMERGER CONVEYANCE EFFECTIVE AUG. 2, 2016 Recorded Jan 28, 2020
From: IL DONG HOLDINGS CO., LTD.
To: IL DONG PHARMACEUTICAL CO., LTD.
Reel/Frame 051727/0568 →
Priority Claims (2)
KR 10-2013-0110170 · Sep 13, 2013 · national
KR 10-2014-0120152 · Sep 11, 2014 · national
Continuity (1)
Reissue 15021336 · Sep 12, 2014