2H-phthalazin-1-one derivatives and drug containing its derivatives as active ingredient

• US 6,677,333 B1
• Filed: 07/25/2001
• Issued: 01/13/2004
• Est. Priority Date: 01/26/1999
• Status: Expired due to Fees

• Current Assignee: ONO Pharmaceutical Company Limited
• Original Assignee: ONO Pharmaceutical Company Limited
• Inventors: Naka, Masao, Takeuchi, Jun, Takahashi, Shinya, Seko, Takuya
• Primary Examiner(s): Raymond, Richard L.
• Application Number:
  US09/889,925
• Time in Patent Office: 902 Days
• Field of Search: 544/237, 544/62, 544/119, 540/575, 514/218, 514/228.2, 514/234.8, 514/248
• US Class Current: 514/218
• CPC Class Codes: A61K 31/502 ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
• CPC Class Codes: C07D 237/32 with oxygen atoms directly attached to carbon atoms of the nitrogen-containing ring
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links

Abstract

Poly(ADP-ribose)polymerase inhibitors containing as the active ingredient 2H-phthalazin-1-one derivatives represented by general formula (I) (wherein each symbol is as defined in the description) or salts thereof. The compounds of the general formula (I) inhibit poly(ADP-ribose)polymerase and are useful as preventives and/or remedies for various ischemic diseases (brain, heart, digestive tract, skeletal muscle, retina, etc.), inflammatory diseases (inflammatory intestinal diseases, multiple encephalosclerosis, arthritis, etc.), nerve degeneration diseases (extrapyramidal disorder, Alzheimer'"'"'s disease, muscular dystrophy, etc.), diabetes, shock, head trauma, renal insufficiency, hyperalgesia, etc. These compounds are also useful as sensitizers for agents against retroviruses (HIV, etc.) and chemotherapy for cancer.

Claims

1. A method for preventing and/or treating diseases induced by poly(ADP-ribose)polymerase, which comprises administering to a subject in need thereof an effective amount of a compound of formula (I)

wherein R¹ is

(i) C1-4 alkyl substituted by hydroxy or amino, or

(ii)—

A¹—

A²—

A³,

in which A¹ is

(i)—

NR³C(O)—

,

(ii)—

NR⁴C(S)—

,

(iii)—

NR⁵SO₂—

,

(iv)—

CH₂—

NR⁶—

,

(v)—

CH₂—

O—

,

(vi)—

OC(O)—

,

(vii)—

CH₂—

NR⁷C(O)—

,

(viii)—

NR⁸C(O)NR⁹—

,

(ix)—

NR¹⁰C(O)O—

,

(x)—

NR¹¹C(S)NR¹²,

(xi)—

N(R¹³)—

, or

with the proviso that the linkage of the right side of each group represented by A¹ binds to A²,

wherein R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴ and R¹⁵ each, independently, is a hydrogen atom, C1-4 alkyl, phenyl or C1-4 alkyl substituted by phenyl,

A² is

(i) C1-8 alkylene,

(ii) C2-8 alkenylene,

(iii) Cyc¹,

(iv)—

(C1-4 alkylene)—

O—

(C1-4 alkylene)—

,

(v)—

(C1-4 alkylene)—

S—

(C1-4 alkylene)—

,

(vi)—

(C1-4 alkylene)—

NR¹⁶—

(C1-4 alkylene)—

,

(vii)—

(Cyc¹)—

(C1-8 alkylene)—

,

(viii)—

(C1-8 alkylene)—

(Cyc¹)—

, or

(ix)—

(C1-4 alkylene)—

(Cyc¹)—

(C1-4 alkylene),

R¹⁶ is a hydrogen atom, C1-8 alkyl, C1-8 alkoxycarbonyl, phenyl or C1-8 alkyl substituted by phenyl,

Cyc¹ is

(i) a 3-10 membered mono-cyclic or bi-cyclic carbocyclic ring, or

(ii) a 3-10 membered mono-cyclic or bi-cyclic hetero ring having 1-4 nitrogen atoms, 1-2 oxygen atoms and/or one sulfur atom,

A³ is

(i) a hydrogen atom,

(ii)—

NR¹⁷R¹⁸,

(iii) Cyc²,

(iv)—

OR¹⁹,

(v)—

COOR²⁰,

(vi)—

CONR²¹R²²,

(vii) C≡

N,

(viii) a halogen atom,

R¹⁷, R²¹ and R²² each, independently, is

(i) a hydrogen atom,

(ii) C1-8 alkyl,

(iii) C2-8 alkenyl,

(iv) C2-8 alkynyl,

(v) Cyc³,

(vi) C1-8 alkoxy,

(vii) C2-8 alkenyloxy,

(viii) C2-8 alkynyloxy, or

(ix) C1-8 alkyl substituted by Cyc³, C1-8 alkoxy, C1-8 alkylthio, C≡

N, hydroxy or 1-3 of halogen atom,

R¹⁸ is

(i) a hydrogen atom,

(ii) C1-8 alkyl,

(iii) C2-8 alkenyl,

(iv) C2-8 alkynyl,

(v) C1-8 alkoxycarbonyl,

(vi) C2-8 acyl,

(vii) C3-8 cycloalkyl,

(viii) C1-8 alkoxycarbonyl substituted by Cyc³ or 1-3 of halogen atom, or

(ix) C1-8 alkyl substituted by C1-8 alkoxy,

R¹⁹ and R²⁰ each, independently, is a hydrogen atom or C1-8 alkyl,

R²³, R²⁴, R²⁵, R²⁶, R²⁷, R²⁸ and R²⁹ each, independently, is a hydrogen atom, C1-4 alkyl, C1-8 alkoxycarbonyl, phenyl, or C1-4 alkyl substituted by phenyl,

Cyc² is a 3-10 membered mono-cyclic or bi-cyclic hetero ring having 1-4 nitrogen atoms, 1-2 oxygen atoms and/or one sulfur atom,

Cyc³ is

(i) a 3-10 membered mono-cyclic or bi-cyclic carbocyclic ring, or

(ii) a 3-10 membered mono-cyclic or bi-cyclic hetero ring having 1-4 nitrogen atoms, 1-2 oxygen atoms and/or one sulfur atom,

the above-mentioned Cyc¹, Cyc² and Cyc³ each, independently, may be optionally substituted by 1-3 of substituents selected from the following (i)-(vii);

(i) C1-8 alkyl,

(ii) C2-8 alkenyl,

(iii) C2-8 alkynyl,

(iv) C1-8 alkoxy,

(v) C1-8 alkoxycarbonyl,

(vi) oxo, and

(vii) C1-8 alkyl substituted by C1-8 alkoxy;

R² is a hydrogen atom, a halogen atom, nitro, hydroxy, —

NR³⁰R³¹, C1-8 alkyl, C1-8 alkoxy, or C1-8 alkyl or C1-8 alkoxy substituted by 1-3 of halogen atoms,

R³⁰ and R³¹ each, independently, is a hydrogen atom, C1-4 alkyl, C1-8 alkoxycarbonyl, phenyl, C1-4 alkyl substituted by phenyl,

with the proviso that, R¹ is not dimethylamino,

or a non-toxic salt thereof and a carrier.

2. A 2H-phthalazin-1-one derivative of the formula (Ia)

wherein R^1a is

(i) C1-4 alkyl substituted by hydroxy or amino, or

(ii) A^1a—

A^2a—

A^3a,

in which A^1a is

(i)—

NR^3aC(O)—

,

(ii) NR^4aC(S)—

,

(iii)—

NR^5aSO₂—

,

(iv)—

CH₂—

NR^6a—

,

(v)—

CH₂—

O—

,

(vi)—

OC(O)—

,

(vii)—

CH₂—

NR^7aC(O)—

,

(viii) NR^8aC(O)NR^9a—

,

(ix)—

NR^10aC(O)O—

,

(x)—

NR^11aC(S)NR^12a—

,

(xi)—

NR(^13a)—

, or

with the proviso that the linkage of the right side of each group represented by A^1a binds to A^2a,

wherein R^3a, R^4a, R^5a, R^6a, R^7a, R^8a, R^9a, R^10a, R^11a, R^12a, R^13a, R^14a and R^15a each, independently, is a hydrogen atom, C1-4 alkyl, phenyl or C1-4 alkyl substituted by phenyl,

A^2a is

(i) C1-8 alkylene,

(ii) C2-8 alkenylene,

(iii) Cyc^1a,

(iv)—

(C1-4 alkylene)—

O—

(C1-4 alkylene)—

,

(v)—

(C1-4 alkylene)—

S—

(C1-4 alkylene)—

,

(vi)—

(C1-4 alkylene)—

NR^16a(C1-4 alkylene)—

,

(vii)—

(Cyc^1a)—

(C1-8 alkylene)—

,

(viii)—

(C1-8 alkylene)—

(Cyc^1a)—

, or

(ix)—

(C1-4 alkylene)—

(Cyc^1a)—

(C1-4 alkylene),

R^16a is a hydrogen atom, C1-8 alkyl, C1-8 alkoxycarbonyl, phenyl or C1-8 alkyl substituted by phenyl,

Cyc^1a is

(i) a 3-10 membered mono-cyclic or bi-cyclic carbocyclic ring, or

(ii) a 3-10 membered mono-cyclic or bi-cyclic hetero ring having 1-4 nitrogen atoms, 1-2 oxygen atoms and/or one sulfur atom,

A^3a is

(i) a hydrogen atom,

(ii)—

N^17aR^18a,

(iii) Cyc^2a,

(iv) OR^19a,

(v)—

COOR^20a,

(vi)—

CONR^21aR^22a,

(vii) C≡

N,

(viii) a halogen atom,

R^17a, R^21a and R^22a each, independently, is

(i) a hydrogen atom,

(ii) C1-8 alkyl,

(iii) C2-8 alkenyl,

(iv) C2-8 alkynyl,

(v) Cyc^3a,

(vi) C1-8 alkoxy,

(vii) C2-8 alkenyloxy,

(viii) C2-8 alkynyloxy, or

(ix) C1-8 alkyl substituted by Cyc^3a, C1-8 alkoxy, C1-8 alkylthio, C≡

N, hydroxy or 1-3 of halogen atom,

R^18a is

(i) a hydrogen atom,

(ii) C1-8 alkyl,

(iii) C2-8 alkenyl,

(iv) C2-8 alkynyl,

(v) C1-8 alkoxycarbonyl,

(vi) C2-8 acyl,

(vii) C3-8 cycloalkyl,

(viii) C1-8 alkoxycarbonyl substituted by Cyc^3a or 1-3 of halogen atom, or

(ix) C1-8 alkyl substituted by C1-8 alkoxy,

R^19a and R²⁰ each, independently, is a hydrogen atom or C1-8 alkyl,

R^23a, R^24a, R^25a, R^26a, R^27a, R^28a and R^29a each independently, is a hydrogen atom, C1-4 alkyl, C1-8 alkoxycarbonyl, phenyl, or C1-4 alkyl substituted by phenyl,

Cyc^2a is a 3-10 membered mono-cyclic or bi-cyclic hetero ring having 1-4 nitrogen atoms, 1-2 oxygen atoms and/or one sulfur atom,

Cyc^3a is

(i) a 3-10 membered mono-cyclic or bi-cyclic carbocyclic ring, or

(ii) a 3-10 membered mono-cyclic or bi-cyclic hetero ring having 1-4 nitrogen atoms, 1-2 oxygen atoms and/or one sulfur atom,

the above-mentioned Cyc^1a, Cyc^2a and Cyc^3a each, independently, may be optionally substituted by 1-3 of substituents selected from the following (i)-(vii);

(i) C1-8 alkyl,

(ii) C2-8 alkenyl,

(iii) C2-8 alkynyl,

(iv) C1-8 alkoxy,

(v) C1-8 alkoxycarbonyl,

(vi) oxo, and

(vii) C1-8 alkyl substituted by C1-8 alkoxy;

R^2a is a hydrogen atom, a halogen atom, nitro, hydroxy, —

NR^30aR^31a, C1-8 alkyl, C1-8 alkoxy, or C1-8 alkyl or C1-8 alkoxy substituted by 1-3 of halogen atoms,

R^30a and R^31aeach, independently, is a hydrogen atom, C1-4 alkyl, C1-8 alkoxycarbonyl, phenyl, C1-4 alkyl substituted by phenyl,

with the proviso that, R^1a is not dimethylamino and the compound is not 4-(2-acetyloxyphenyl)-2H-phthalazin-1-one,

or a non-toxic salt thereof.

3. A compound according to claim 2,

in which

R^16a is a hydrogen atom, C1-4 alkyl, C1-8 alkoxycarbonyl, phenyl, or C1-4 alkyl substituted by phenyl,

Cyc^1a is

(i) a 3-10 membered mono-cyclic or bi-cyclic carbocyclic ring, or

(ii) a 3-10 membered mono-cyclic or bi-cyclic hetero ring having 1-4 nitrogen atoms, one oxygen atoms and/or one sulfur atom, and Cyc^1a may be substituted by C1-8 alkoxycarbonyl,

A^3a is

(i) a hydrogen atom,

(ii)— N^17aR^18a,

(iii) Cyc^2a,

(iv)—

OR^19a,

(v)—

COOR^20a,

(vi)—

CONR^21aR^22a,

R^17a, R^21a and R^22a each, independently, is a hydrogen atom, C1-4 alkyl, phenyl, or C1-4 alkyl substituted by phenyl,

R^18a is a hydrogen atom, C1-4 alkyl, C1-8 alkoxycarbonyl, C2-5 acyl, or C1-4 alkoxycarbonyl substituted by phenyl,

R^19a and R^20a each, independently, is a hydrogen atom or C1-4 alkyl,

Cyc^2a is a 3-10 membered mono-cyclic or bi-cyclic hetero ring having 1-4 nitrogen atoms, one oxygen atoms and/or one sulfur atom, substituted by C1-8 alkoxycarbonyl,

R^2a is a hydrogen atom, a halogen atom, nitro, or NR^30aR^31a.

4. A compound according to claim 2, wherein

R^1a is —

A^1a—

A^2a—

A^3a,

A^1a and A^2a is the same meaning as claim 2 defined,

A^3a is (ii)—

NR^17aR^16a, (iii) Cyc^2a, (vii)—

C≡

N, or (viii) a halogen atom, with the proviso that, when A^3a is NR^17aR^18a, then R^17a represents the groups except a hydrogen atom, C1-4 alkyl, phenyl, or C1-4 alkyl substituted by phenyl, Cyc^2a is a 3-10 membered mono-cyclic or bi-cyclic hetero ring containing 1-4 nitrogen atoms, 1-2 oxygen atoms and/or one sulfur atom, substituted by 1-3 of substituent selected from C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C1-8 alkoxy, oxo, or C1-8 alkyl substituted by C1-8 alkoxy (with the proviso that when the substituent is selected from C1-8 alkyl, C1-8 alkoxy, or C1-8 alkyl substituted by C1-8 alkoxy, then the number of the substituent is 2 or

     3).

5. A compound according to claim 2,

wherein

R^2a is hydroxy, C1-8 alkyl, C1-8 alkoxy, or

C1-8 alkyl or C1-8 alkoxy substituted by 1-3 of halogen.

6. A compound according to claim 2,

wherein R^1a is —

A^1a—

A^2a—

A^3a and

A^1a is —

NR^3aC(O)—

.

7. A compound according to claim 2, which is

(1) 4-(3-(Hydroxymethyl)phenyl)-2H-phthalazin-1-one,

(2) 4-(3-(Aminomethyl)phenyl)-2H-phthalazin-1-one,

(3) 4-(3-(Dimethylaminomethyl)phenyl)-2H-phthalazin-1-one,

(4) 4-(3-(5-(t-Butoxycarbonylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(5) 4-(3-(2-(t-Butoxycarbonylamino)acetylamino)phenyl)-2H-phthalazin-1-one,

(6) 4-(3-(4-(Benzyloxycarbonylamino)butyrylamino)phenyl)-2H-phthalazin-1-one,

(7) 4-(3-(6-(t-Butoxycarbonylamino)hexanoylamino)phenyl)-2H-phthalazin-1-one,

(8) 4-(3-(3-(Benzyloxycarbonylamino)propionylamino)phenyl)-2H-phthalazin-1-one,

(9) 4-(3-(2-(t-Butoxycarbonylamino)acetylaminomethyl)phenyl)-2H-phthalazin-1-one,

(10) 4-(3-(3-(t-Butoxycarbonylamino)propionylaminomethyl)phenyl)-2H-phthalazin-1-one,

(11) 4-(3-(1-t-Butoxycarbonylpiperidin-4-ylcarbonylamino)phenyl)-2H-phthalazin-1-one,

(12) 4-(3-(4-(t-Butoxycarbonylamino)butyrylaminomethyl)phenyl)-2H-phthalazin-1-one,

(13) 4-(3-(5-(t-Butoxycarbonylamino)valerylaminomethyl)phenyl)-2H-phthalazin-1-one,

(14) 4-(2-(5-(t-Butoxycarbonylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(15) 4-(3-(3-(Indol-3-yl)propionylamino)phenyl)-2H-phthalazin-1-one,

(16) 4-(3-(5-(Morpholin-4-yl)valerylamino)phenyl)-2H-phthalazin-1-one,

(17) 4-(3-(2-(Pyridin-4-yl)acetylamino)phenyl)-2H-phthalazin-1-one,

(18) 4-(3-(5-(Pyrrolidin-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,

(19) 4-(3-(5-(Dimethylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(20) 4-(3-(3-(Pyridin-3-yl)propionylamino)phenyl)-2H-phthalazin-1-one,

(21) 4-(3-(5-(N-Methyl-N-t-butoxycarbonylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(22) 4-(3-(2-(2-(t-Butoxycarbonylamino)ethylthio)acetylamino)phenyl)-2H-phthalazin-1-one,

(23) 4-(3-(2-(N-(2-(t-Butoxycarbonylamino)ethyl)-N-t-butoxycarbonylamino)acetylamino)phenyl)-2H-phthalazin-1-one,

(24) 4-(3-(5-(t-Butoxycarbonylamino)valeryloxy)phenyl)-2H-phthalazin-1-one,

(25) 4-(3-(2-(3-(t-Butoxycarbonylamino)phenyl)acetylamino)phenyl)-2H-phthalazin-1-one,

(26) 4-(3-(3-(t-Butoxycarbonylaminomethyl)benzoylamino)phenyl)-2H-phthalazin-1-one,

(27) 4-(3-(trans-4-(t-Butoxycarbonylaminomethyl)cyclohexylcarbonylamino)phenyl)-2H-phthalazin-1-one,

(28) 4-(3-(4-(t-Butoxycarbonylamino)cyclohexylcarbonylamino)phenyl)-2H-phthalazin-1-one,

(29) 4-(3-(4-(t-Butoxycarbonylaminomethyl)benzoylamino)phenyl)-2H-phthalazin-1-one,

(30) 4-(3-(2-(4-(t-Butoxycarbonylamino)phenyl)acetylamino)phenyl)-2H-phthalazin-1-one,

(31) 4-(3-((E)-3-(1-(t-Butoxycarbonyl)imidazol-4-yl)propenoylamino)phenyl)-2H-phthalazin-1-one,

(32) 4-(3-(5-Aminovalerylamino)phenyl)-2H-phthalazin-1-one,

(33) 4-(3-(2-Aminoacetylamino)phenyl)-2H-phthalazin-1-one,

(34) 4-(3-(6-Aminohexanoylamino)phenyl)-2H-phthalazin-1-one,

(35) 4-(3-(2-Aminoacetylaminomethyl)phenyl)-2H-phthalazin-1-one,

(36) 4-(3-(3-Aminopropionylaminomethyl)phenyl)-2H-phthalazin-1-one,

(37) 4-(3-(Piperidin-4-ylcarbonylamino)phenyl)-2H-phthalazin-1-one,

(38) 4-(3-(4-Aminobutyrylaminomethyl)phenyl)-2H-phthalazin-1-one,

(39) 4-(3-(5-Aminovalerylaminomethyl)phenyl)-2H-phthalazin-1-one,

(40) 4-(2-(5-Aminovalerylamino)phenyl)-2H-phthalazin-1-one,

(41) 4-(3-(5-(Methylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(42) 4-(3-(2-(2-Aminoethylthio)acetylamino)phenyl)-2H-phthalazin-1-one,

(43) 4-(3-(2-(2-Aminoethylamino)acetylamino)phenyl)-2H-phthalazin-1-one,

(44) 4-(3-(5-Aminovaleryloxy)phenyl)-2H-phthalazin-1-one,

(45) 4-(3-(2-(3-Aminophenyl)acetylamino)phenyl)-2H-phthalazin-1-one,

(46) 4-(3-(3-(Aminomethyl)benzoylamino)phenyl)-2H-phthalazin-1-one,

(47) 4-(3-(trans-4-(Aminomethyl)cyclohexylcarbonylamino)phenyl)-2H-phthalazin-1-one,

(48) 4-(3-(4-Aminocyclohexylcarbonylamino)phenyl)-2H-phthalazin-1-one,

(49) 4-(3-(4-(Aminomethyl)benzoylamino)phenyl)-2H-phthalazin-1-one,

(50) 4-(3-(2-(4-Aminophenyl)acetylamino)phenyl)-2H-phthalazin-1-one,

(51) 4-(3-((E)-3-(Imidazol-4-yl)propenoylamino)phenyl)-2H-phthalazin-1-one,

(52) 4-(3-(Acetylamino)phenyl)-2H-phthalazin-1-one,

(53) 4-(3-(Hexanoylamino)phenyl)-2H-phthalazin-1-one,

(54) 4-(3-(Benzoylamino)phenyl)-2H-phthalazin-1-one,

(55) 4-(3-(Butyrylamino)phenyl)-2H-phthalazin-1-one,

(56) 4-(3-(Valerylamino)phenyl)-2H-phthalazin-1-one,

(57) 4-(3-(Mesylamino)phenyl)-2H-phthalazin-1-one,

(58) 4-(3-(Butylsulfonylamino)phenyl)-2H-phthalazin-1-one,

(59) 4-(2-(Acetylamino)phenyl)-2H-phthalazin-1-one,

(60) 4-(4-Chloro-3-(acetylamino)phenyl)-2H-phthalazin-1-one,

(61) 4-(3-(4-(Methoxycarbonyl)butyrylamino)phenyl)-2H-phthalazin-1-one,

(62) 4-(3-(Acetoxy)phenyl)-2H-phthalazin-1-one,

(63) 4-(3-(4-Aminobutyrylamino)phenyl)-2H-phthalazin-1-one,

(64) 4-(3-(3-Aminopropionylamino)phenyl)-2H-phthalazin-1-one,

(65) 4-(3-(4-Carboxybutyrylamino)phenyl)-2H-phthalazin-1-one,

(66) 4-(3-(5-Hydroxyvalerylamino)phenyl)-2H-phthalazin-1-one,

(67) 4-(3-(4-(t-Butoxycarbonylamino)butylaminomethyl)phenyl)-2H-phthalazin-1-one,

(68) 4-(3-(4-Aminobutylaminomethyl)phenyl)-2H-phthalazin-1-one,

(69) 4-(3-(3-Ethyl-2-thioureido)phenyl)-2H-phthalazin-1-one,

(70) 4-(3-(3-Ethylureido)phenyl)-2H-phthalazin-1-one,

(71) 4-(3-(Ethoxycarbonylamino)phenyl)-2H-phthalazin-1-one,

(72) 4-(3-(5-(t-Butoxycarbonylamino)pentylamino)phenyl)-2H-phthalazin-1-one,

(73) 4-(3-(5-Aminopentylamino)phenyl)-2H-phthalazin-1-one,

(74) 4-(3-(Propylthiocarbonylamino)phenyl)-2H-phthalazin-1-one,

(75) 4-(3-(5-(Acetylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(76) 4-(3-(3-(3-t-Butoxycarbonylaminopropyl)-2-thioureido)phenyl)-2H-phthalazin-1-one,

(77) 4-(3-(3-(3-Aminopropyl)-2-thioureido)phenyl)-2H-phthalazin-1-one,

(78) 4-(3-(6-Dimethylaminohexanoylamino)phenyl)-2H-phthalazin-1-one,

(79) 4-(3-(5-(Thiazolidin-3-yl)valerylamino)phenyl)-2H-phthalazin-1-one,

(80) 4-(3-(5-(Furan-2-ylmethylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(81) 4-(3-(5-(N-Methyl-N-propylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(82) 4-(3-(5-(2-Dimethylaminoethylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(83) 4-(3-(5-Diethylaminovalerylamino)phenyl)-2H-phthalazin-1-one,

(84) 4-(3-(5-(Azetidine-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,

(85) 4-(3-(5-Benzylaminovalerylamino)phenyl)-2H-phthalazin-1-one,

(86) 4-(3-(5-(N-(Furan-2-yl)methyl-N-methylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(87) 4-(3-(5-(N-t-Butyl-N-methylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(88) 4-(3-(5-(N-Isobutyl-N-methylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(89) 4-(3-(4-Morpholinobutyrylamino)phenyl)-2H-phthalazin-1-one,

(90) 4-(3-(5-(N-Ethyl-N-methylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(91) 4-(3-(5-(Thiophen-2-ylmethylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(92) 4-(3-(5-(N-Methyl-N-isopropylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(93) 4-(3-(5-(Tetrahydrofuran-2-ylmethylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(94) 4-(3-(5-t-Butylaminovalerylamino)phenyl)-2H-phthalazin-1-one,

(95) 4-(3-(5-sec-Butylaminovalerylamino)phenyl)-2H-phthalazin-1-one,

(96) 4-(3-(5-Ethylaminovalerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,

(97) 4-(3-(5-Butylaminovalerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,

(98) 4-(3-(5-Morpholinovalerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,

(99) 4-(3-(5-Thiomorpholinovalerylamino)phenyl)-2H-phthalazin-1-one,

(100) 4-(3-(5-(4-Methylpiperazin-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,

(101) 4-(3-(5-Dimethylaminovalerylamino)4-fluorophenyl)-2H-phthalazin-1-one,

(102) 4-(3-(5-(N-Methyl-N-propylamino)valerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,

(103) 4-(3-(5-Isobutylaminovalerylamino)phenyl)-2H-phthalazin-1-one,

(104) 4-(3-(5-(Piperidin-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,

(105) 4-(3-(5-(Perhydroazepin-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,

(106) 4-(3-(5-(N-Ethyl-N-2-methoxyethylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(107) 4-(3-(5-Morpholinovalerylamino)-4-fluorophenyl)-2H-phthalazin-1-one,

(108) 4-(3-(5-(1,2,5,6-Tetrahydropyridin-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,

(109) 4-(3-(5-(Pyrrolidin-1-yl)valerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,

(110) 4-(3-(5-((2S)-2-Methoxymethylpyrrolidin-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,

(111) 4-(3-(5-(1,2,3-Triazol-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,

(112) 4-(3-(5-(N-2-Methoxyethyl-N-methylamino)valerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,

(113) 4-(3-(5-(Imidazol-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,

(114) 4-(3-(5-(3-Methoxypyrrolidin-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,

(115) 4-(3-(5-(3-Methoxypiperidin-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,

(116) 4-(3-(5-((2R)2-Methoxymethylpyrrolidin-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,

(117) 4-(3-(5-(4-Methoxypiperidin-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,

(118) 4-(3-(5-Isobutylaminovalerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,

(119) 4-(3-(5-(Pyrrolidin-1-yl)valerylamino)-4-fluorophenyl)-2H-phthalazin-1-one,

(120) 4-(3-(6-Morpholinohexanoylamino)phenyl)-2H-phthalazin-1-one,

(121) 4-(3-(5-(Perhydroazepin-1-yl)valerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,

(122) 4-(3-(5-(2-Hydroxyethylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(123) 4-(3-(5-(3-Methoxypiperidin-1-yl)valerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,

(124) 4-(3-(5-((3R)-3-Methoxypiperidin-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,

(125) 4-(3-(5-((3S)-3-Methoxypiperidin-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,

(126) 4-(3-(5-(3-Methoxypiperidin-1-yl)valerylamino)-4-fluorophenyl)-2H-phthalazin-1-one,

(127) 4-(3-(5-(3-Methoxymethylpiperidin-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,

(128) 4-(3-(4-Dimethylaminobutyrylamino)-4-chlorophenyl)-2H-phthalazin-1-one,

(129) 4-(3-(4-Dimethylaminobutyrylamino)phenyl)-2H-phthalazin-1-one,

(130) 4-(4-Dimethylamino-3-(5-dimethylaminovalerylamino)phenyl)-2H-phthalazin-1-one,

(131) 4-(3-(5-Dimethylaminovalerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,

(132) 4-(3-(3-Morpholinopropylsulfonylamino)phenyl)-2H-phthalazin-1-one,

(133) 4-(3-(4-Morpholinobutylsulfonylamino)phenyl)-2H-phthalazin-1-one,

(134) 4-(3-(5-Morpholino-2,2-dimethylvalerylamino)phenyl)-2H-phthalazin-1-one,

(135) 4-(3-(4-Dimethylaminobutylsulfonylamino)phenyl)-2H-phthalazin-1-one,

(136) 4-(3-(4-Morpholinobutylsulfonylamino)-4-fluorophenyl)-2H-phthalazin-1-one,

(137) 4-(3-(4-(3-Methoxypiperidin-1-yl)butylsulfonylamino)phenyl)-2H-phthalazin-1-one,

(138) 4-(3-(5-(N-t-Butoxycarbonyl-N-ethylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(139) 4-(3-(5-(N-t-Butoxycarbonyl-N-propylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(140) 4-(3-(5-(N-Isopropyl-N-t-butoxycarbonylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(141) 4-(3-(7-t-Butoxycarbonylaminoheptanoylamino)phenyl)-2H-phthalazin-1-one,

(142) 4-(3-(2-(2-t-Butoxycarbonylaminoethyloxy)acetylamino)phenyl)-2H-phthalazin-1-one,

(143) 4-(3-(5-(N-Butyl-N-t-butoxycarbonylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(144) 4-(3-(5-t-Butoxycarbonylaminovalerylamino)-4-dipropylaminophenyl)-2H-phthalazin-1-one,

(145) 4-(3-(6-(N-Methyl-N-t-butoxycarbonylamino)hexanoylamino)phenyl)-2H-phthalazin-1-one,

(146) 4-(3-((3E)-5-t-Butoxycarbonylaminopentenoylamino)phenyl)-2H-phthalazin-1-one,

(147) 4-(3-(4-Amidinophenylcarbonylamino)phenyl)-2H-phthalazin-1-one,

(148) 4-(3-(2-(2-Dimethylaminoethylthio)acetylamino)phenyl)-2H-phthalazin-1-one,

(149) 4-(3-(4-Carbamoylbutyrylamino)phenyl)-2H-phthalazin-1-one,

(150) 4-(3-(4-(N-t-Butoxycarbonyl-N-methylamino)butyrylamino)phenyl)-2H-phthalazin-1-one,

(151) 4-(3-((2E)-5-t-Butoxycarbonylamino-2-pentenoylamino)phenyl)-2H-phthalazin-1-one,

(152) 4-(3-(3-(t-Butoxycarbonylamino)propionylamino)phenyl)-2H-phthalazin-1-one,

(153) 4-(3-(trans-2-Benzyloxycarbonylaminomethylcyclopropylcarbonylamino)phenyl)-2H-phthalazin-1-one,

(154) 4-(3-(2-(2-Morpholinoethylthio)acetylamino)phenyl)-2H-phthalazin-1-one,

(155) 4-(3-(2-(2-Morpholinoethyloxy)acetylamino)phenyl)-2H-phthalazin-1-one,

(156) 4-(3-(2-(2-Morpholinoethylthio)-2-methylpropionylamino)phenyl)-2H-phthalazin-1-one,

(157) 4-(3-(trans-2-Aminomethylcyclopropylcarbonylamino)phenyl)-2H-phthalazin-1-one,

(158) 4-(3-(5-(2-Methoxyethylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(159) 4-(3-(5-(N-2-Methoxyethyl-N-methylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(160) 4-(3-(5-(N-2-Hydroxyethyl-N-methylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(161) 4-(3-(5-t-Butoxycarbonylaminovalerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,

(162) 4-(3-(N-(5-t-Butoxycarbonylaminovaleryl)-N-methylamino)phenyl)-2H-phthalazin-1-one,

(163) 4-(3-(5-(2,3-Bis(t-butoxycarbonyl)guanidino)valerylamino)phenyl)-2H-phthalazin-1-one,

(164) 4-(3-(5-Ethylaminovalerylamino)phenyl)-2H-phthalazin-1-one,

(165) 4-(3-(5-Propylaminovalerylamino)phenyl)-2H-phthalazin-1-one,

(166) 4-(3-(5-Isopropylaminovalerylamino)phenyl)-2H-phthalazin-1-one,

(167) 4-(3-(7-Aminoheptanoylamino)phenyl)-2H-phthalazin-1-one,

(168) 4-(3-(2-(2-Aminoethyloxy)acetylamino)phenyl)-2H-phthalazin-1-one,

(169) 4-(3-(5-Butylaminovalerylamino)phenyl)-2H-phthalazin-1-one,

(170) 4-(3-(5-Aminovalerylamino)-4-dipropylaminophenyl)-2H-phthalazin-1-one,

(171) 4-(3-(6-Methylaminohexanoylamino)phenyl)-2H-phthalazin-1-one,

(172) 4-(3-((3E)-5-Amino-3-pentenoylamino)phenyl)-2H-phthalazin-1-one,

(173) 4-(3-(4-Methylaminobutyrylamino)phenyl)-2H-phthalazin-1-one,

(174) 4-(3-((2E)-5-Amino-2-pentenoylamino)phenyl)-2H-phthalazin-1-one,

(175) 4-(3-(5-Aminovalerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,

(176) 4-(3-(N-5-Aminovaleryl-N-methylamino)phenyl)-2H-phthalazin-1-one,

(177) 4-(3-(5-Guanidinovalerylamino)phenyl)-2H-phthalazin-1-one,

(178) 4-(3-(3-(2-Morpholinoethyl)-2-thioureido)phenyl)-2H-phthalazin-1-one,

(179) 4-(3-(3-(3-Morpholinopropyl)ureido)phenyl)-2H-phthalazin-1-one,

(180) 4-(3-(3-(3-Morpholinopropyl)-2-thioureido)phenyl)-2H-phthalazin-1-one,

(181) 4-(3-(2-Morpholinoethyloxycarbonylamino)phenyl)-2H-phthalazin-1-one,

(182) 4-(3-(2-(2-(Piperidin-1-yl)ethyloxy)acetyl)aminophenyl)-2H-phthalazin-1-one,

(183) 4-(3-(5-(4-Methoxypiperidin-1-yl)valerylamino-4-chlorophenyl)-2H-phthalazin-1-one, or

(184) 4-(3-(5-(4-Methoxypiperidin-1-yl)valerylamino-4-fluorophenyl)-2H-phthalazin-1-one,

or a non-toxic salt thereof.

8. A compound according to claim 2, which is

(1) 4-(3-(5-Bromovalerylamino)phenyl)-2H-phthalazin-1-one,

(2) 4-(3-(5-Bromovalerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,

(3) 4-(3-(5-Cyclohexylaminovalerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,

(4) 4-(3-(5-Cyclopentylaminovalerylamino)phenyl)-2H-phthalazin-1-one,

(5) 4-(3-(5-Cyclohexylaminovalerylamino)phenyl)-2H-phthalazin-1-one,

(6) 4-(3-(5-(N-Methyl-N-2-propynylamino)valerylaminomethyl)-2H-phthalazin-1-one,

(7) 4-(3-(5-(2,2,2-Trifluoroethylaminovalerylamino)phenyl)-2H-phthalazin-1-one,

(8) 4-(3-(5-Cyclopropylaminovalerylamino)phenyl)-2H-phthalazin-1-one,

(9) 4-(3-(5-(Cyclohexylmethylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(10) 4-(3-(5-(N,N-Bis(2-methoxyethyl)amino)valerylamino)phenyl)-2H-phthalazin-1-one,

(11) 4-(3-(5—

Neopentylaminovalerylamino)phenyl)-2H-phthalazin-1-one,

(12) 4-(3-(5-(2-Propynylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(13) 4-(3-(5-Cyclopropylmethylaminovalerylamino)phenyl)-2H-phthalazin-1-one,

(14) 4-(3-(5-Cyclopentylmethylaminovalerylamino)phenyl)-2H-phthalazin-1-one,

(15) 4-(3-(5-Cyclobutylaminovalerylamino)phenyl)-2H-phthalazin-1-one,

(16) 4-(3-(5-(2-Fluoroethylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(17) 4-(3-(5-(2-Methyl-2-propenylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(18) 4-(3-(5-(2-(1-Cyclohexen-1-yl)ethylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(19) 4-(3-(5-(1,2-Dimethylpropylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(20) 4-(3-(5-Cyclopropylaminovalerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,

(21) 4-(3-(5-(2-Fluoroethylamino)valerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,

(22) 4-(3-(5-(2-Methyl-2-propenylamino)valerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,

(23) 4-(3-(5-(2-Propenylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(24) 4-(3-(5-(2-Propynylamino)valerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,

(25) 4-(3-(5-(2-Propenyloxyamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(26) 4-(3-(5-Cycloheptylaminovalerylamino)phenyl)-2H-phthalazin-1-one,

(27) 4-(3-(5-(2-Cyanoethylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(28) 4-(3-(5-Cyclobutylaminovalerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,

(29) 4-(3-(5-(2,6-Dimethylmorpholin-4-yl)valerylamino)phenyl)-2H-phthalazin-1-one,

(30) 4-(3-(5-(2-Ethyl-4-methylimidazol-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,

(31) 4-(3-(5-Cyclopentylaminovalerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,

(32) 4-(3-(5-(2-Methylthioethylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(33) 4-(3(5-(N-Methyl-N-2-propynylamino)valerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,

(34) 4-(3-(5-(1-Methoxymethylcyclopentylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(35) 4-(3-(5-(Tetrahydropyran-4-ylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(36) 4-(3-(5-(2-Methoxycyclohexylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(37) 4-(3-(5-((1S, 2S)-2-Methoxycyclopentylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(38) 4-(3-(5-(2-Propenylamino)valerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,

(39) 4-(3(5-(2-Fluoroethylamino)valerylamino)-4-fluorophenyl)-2H-phthalazin-1-one,

(40) 4-(3-(5-(Tetrahydropyran-4-ylamino)valerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,

(41) 4-(3-(5-(3-Methylbutylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(42) 4-(3-(5-(N-Methyl-N-tetrahydropyran-4-yl)aminovalerylamino)phenyl)-2H-phthalazin-1-one,

(43) 4-(3-(5-(Piperidin-4-one-1-yl)valerylamino)phenyl)-2H-phthalazin-1-one,

(44) 4-(3-(5-((3R)-Tetrahydrofuran-3-ylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(45) 4-(3-(5-((3S)-Tetrahydrofuran-3-ylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(46) 4-(3-(4-Cyanobutyrylamino)-4-dimethylaminophenyl)-2H-phthalazin-1-one,

(47) 4-(3-(4-Cyanobutyrylamino)phenyl)-2H-phthalazin-1-one,

(48) 4-(3-(5-(N-3-Methyl-2-butenyl-N-t-butoxycarbonylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(49) 4-(3-(5-(N-2-Butynyl-N-t-butoxycarbonylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(50) 4-(3-(5-(N-Benzyloxycarbonyl-N-tetrahydrofuran-3-ylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(51) 4-(3-(5-(Tetrahydrofuran-3-ylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

(52) 4-(3-(5-(1,3-Dioxoisoindolin-2-yl)valerylamino)-4-chlorophenyl)-2H-phthalazin-1-one,

(53) 4-(3-(5-(3-Methyl-2-butenylamino)valerylamino)phenyl)-2H-phthalazin-1-one, or

(54) 4-(3-(5-(2-Butynylamino)valerylamino)phenyl)-2H-phthalazin-1-one,

or a non-toxic salt thereof.

9. A compound according to claim 2, which is

(1) 4-(3-(5-Dimethylaminovalerylamino)-4-methoxyphenyl)-2H-phthalazin-1-one,

(2) 4-(3-(5-Dimethylaminovalerylamino)-4-hydroxyphenyl)-2H-phthalazin-1-one,

(3) 4-(3-(5-Dimethylaminovalerylamino)-4-methylphenyl)-2H-phthalazin-1-one,

(4) 4-(3-(5-Morpholinovalerylamino)-4-methylphenyl)-2H-phthalazin-1-one,

(5) 4-(3-(5-(3-Methoxypiperidin-1-yl)valerylamino)-4-methylphenyl)-2H-phthalazin-1-one,

(6) 4-(3-(4-Morpholinobutylsulfonylamino)-4-methoxyphenyl)-2H-phthalazin-1-one,

(7) 4-(3-(4-Morpholinobutylsulfonylamino)-4-methylphenyl)-2H-phthalazin-1-one, or

(8) 4-(3-(5-(4-Methoxypiperidin-1-yl)valerylamino-4-methylphenyl)-2H-phthalazin-1-one,

or a non-toxic salt thereof.