JP4778439B2 - 抗癌剤としてのキナゾリノン化合物 - Google Patents
抗癌剤としてのキナゾリノン化合物 Download PDFInfo
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- JP4778439B2 JP4778439B2 JP2006541684A JP2006541684A JP4778439B2 JP 4778439 B2 JP4778439 B2 JP 4778439B2 JP 2006541684 A JP2006541684 A JP 2006541684A JP 2006541684 A JP2006541684 A JP 2006541684A JP 4778439 B2 JP4778439 B2 JP 4778439B2
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- JP
- Japan
- Prior art keywords
- substituted
- unsubstituted
- oxo
- chloro
- dihydroquinazolin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical class C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 title abstract description 13
- 239000002246 antineoplastic agent Substances 0.000 title description 9
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- -1 hydroxy, amino Chemical group 0.000 claims description 113
- 150000001875 compounds Chemical class 0.000 claims description 101
- 125000000217 alkyl group Chemical group 0.000 claims description 80
- 125000003118 aryl group Chemical group 0.000 claims description 61
- 125000000623 heterocyclic group Chemical group 0.000 claims description 55
- 229910052739 hydrogen Inorganic materials 0.000 claims description 38
- 239000001257 hydrogen Substances 0.000 claims description 38
- 125000001072 heteroaryl group Chemical group 0.000 claims description 36
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 29
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 29
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 24
- 125000003342 alkenyl group Chemical group 0.000 claims description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- 125000003545 alkoxy group Chemical group 0.000 claims description 19
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 19
- 125000000304 alkynyl group Chemical group 0.000 claims description 18
- 125000005842 heteroatom Chemical group 0.000 claims description 18
- 125000001424 substituent group Chemical group 0.000 claims description 15
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 14
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 12
- 125000003282 alkyl amino group Chemical group 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 11
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 10
- 150000002431 hydrogen Chemical group 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
- 125000003277 amino group Chemical group 0.000 claims description 7
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- 125000005157 alkyl carboxy group Chemical group 0.000 claims description 6
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 6
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 6
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 5
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 5
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 5
- 125000004104 aryloxy group Chemical group 0.000 claims description 5
- 125000002837 carbocyclic group Chemical group 0.000 claims description 5
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 5
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 5
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 4
- 125000001188 haloalkyl group Chemical group 0.000 claims description 4
- 125000006186 3,5-dimethyl benzyl group Chemical group [H]C1=C(C([H])=C(C([H])=C1C([H])([H])[H])C([H])([H])*)C([H])([H])[H] 0.000 claims description 3
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 3
- 125000001960 7 membered carbocyclic group Chemical group 0.000 claims description 3
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 3
- 125000004422 alkyl sulphonamide group Chemical group 0.000 claims description 3
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 3
- 150000003857 carboxamides Chemical class 0.000 claims description 3
- 125000004112 carboxyamino group Chemical group [H]OC(=O)N([H])[*] 0.000 claims description 3
- 125000000449 nitro group Chemical class [O-][N+](*)=O 0.000 claims description 3
- 238000006467 substitution reaction Methods 0.000 claims description 3
- YELDUWMYYRJMJD-UHFFFAOYSA-N 2-sulfamoylguanidine Chemical compound NC(N)=NS(N)(=O)=O YELDUWMYYRJMJD-UHFFFAOYSA-N 0.000 claims description 2
- 125000003852 3-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Cl)=C1[H])C([H])([H])* 0.000 claims description 2
- 125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 claims description 2
- 125000006497 3-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000006500 3-trifluoromethoxy benzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC(F)(F)F)=C1[H])C([H])([H])* 0.000 claims description 2
- 125000006495 3-trifluoromethyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])*)C(F)(F)F 0.000 claims description 2
- 125000005099 aryl alkyl carbonyl group Chemical group 0.000 claims description 2
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 2
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 2
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 claims description 2
- 125000004992 haloalkylamino group Chemical group 0.000 claims description 2
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 2
- 125000005223 heteroarylcarbonyl group Chemical group 0.000 claims description 2
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 2
- POONXXSQQOXHCC-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-(3-benzyl-7-chloro-4-oxoquinazolin-2-yl)-2-(dimethylamino)-2-oxoethyl]-4-methylbenzamide Chemical compound N=1C2=CC(Cl)=CC=C2C(=O)N(CC=2C=CC=CC=2)C=1C(C(=O)N(C)C)N(CCCN)C(=O)C1=CC=C(C)C=C1 POONXXSQQOXHCC-UHFFFAOYSA-N 0.000 claims description 2
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 2
- WITIKSHMUIOFJB-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-[7-chloro-3-[(3,5-dimethylphenyl)methyl]-4-oxoquinazolin-2-yl]-2-[ethyl(methyl)amino]-2-oxoethyl]-4-methylbenzamide Chemical compound N=1C2=CC(Cl)=CC=C2C(=O)N(CC=2C=C(C)C=C(C)C=2)C=1C(C(=O)N(C)CC)N(CCCN)C(=O)C1=CC=C(C)C=C1 WITIKSHMUIOFJB-UHFFFAOYSA-N 0.000 claims 2
- 125000006512 3,4-dichlorobenzyl group Chemical group [H]C1=C(Cl)C(Cl)=C([H])C(=C1[H])C([H])([H])* 0.000 claims 1
- 125000006288 3,5-difluorobenzyl group Chemical group [H]C1=C(F)C([H])=C(C([H])=C1F)C([H])([H])* 0.000 claims 1
- 150000000660 7-membered heterocyclic compounds Chemical class 0.000 claims 1
- 125000004967 formylalkyl group Chemical group 0.000 claims 1
- AVHOJTLHZDDVOA-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-(3-benzyl-7-chloro-4-oxoquinazolin-2-yl)-2-(diethylamino)-2-oxoethyl]-4-bromobenzamide Chemical compound N=1C2=CC(Cl)=CC=C2C(=O)N(CC=2C=CC=CC=2)C=1C(C(=O)N(CC)CC)N(CCCN)C(=O)C1=CC=C(Br)C=C1 AVHOJTLHZDDVOA-UHFFFAOYSA-N 0.000 claims 1
- VEEJEPDQIUHADP-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-(3-benzyl-7-chloro-4-oxoquinazolin-2-yl)-2-(diethylamino)-2-oxoethyl]-4-methylbenzamide Chemical compound N=1C2=CC(Cl)=CC=C2C(=O)N(CC=2C=CC=CC=2)C=1C(C(=O)N(CC)CC)N(CCCN)C(=O)C1=CC=C(C)C=C1 VEEJEPDQIUHADP-UHFFFAOYSA-N 0.000 claims 1
- XSYDZTXTTOMYBB-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-(3-benzyl-7-chloro-4-oxoquinazolin-2-yl)-2-(dimethylamino)-2-oxoethyl]-4-bromobenzamide Chemical compound N=1C2=CC(Cl)=CC=C2C(=O)N(CC=2C=CC=CC=2)C=1C(C(=O)N(C)C)N(CCCN)C(=O)C1=CC=C(Br)C=C1 XSYDZTXTTOMYBB-UHFFFAOYSA-N 0.000 claims 1
- ZWNDSENQXXDXCW-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-(3-benzyl-7-chloro-4-oxoquinazolin-2-yl)-2-(dimethylamino)-2-oxoethyl]-4-chlorobenzamide Chemical compound N=1C2=CC(Cl)=CC=C2C(=O)N(CC=2C=CC=CC=2)C=1C(C(=O)N(C)C)N(CCCN)C(=O)C1=CC=C(Cl)C=C1 ZWNDSENQXXDXCW-UHFFFAOYSA-N 0.000 claims 1
- MEAPCCYRNOYZDP-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-(3-benzyl-7-chloro-4-oxoquinazolin-2-yl)-2-[ethyl(methyl)amino]-2-oxoethyl]-4-methylbenzamide Chemical compound N=1C2=CC(Cl)=CC=C2C(=O)N(CC=2C=CC=CC=2)C=1C(C(=O)N(C)CC)N(CCCN)C(=O)C1=CC=C(C)C=C1 MEAPCCYRNOYZDP-UHFFFAOYSA-N 0.000 claims 1
- LWYJDXDVXHJUGN-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-(3-benzyl-7-chloro-4-oxoquinazolin-2-yl)-2-morpholin-4-yl-2-oxoethyl]-4-bromobenzamide Chemical compound C=1C=C(Br)C=CC=1C(=O)N(CCCN)C(C=1N(C(=O)C2=CC=C(Cl)C=C2N=1)CC=1C=CC=CC=1)C(=O)N1CCOCC1 LWYJDXDVXHJUGN-UHFFFAOYSA-N 0.000 claims 1
- IFHLXHPKUGAEAO-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-(3-benzyl-7-chloro-4-oxoquinazolin-2-yl)-2-morpholin-4-yl-2-oxoethyl]-4-chlorobenzamide Chemical compound C=1C=C(Cl)C=CC=1C(=O)N(CCCN)C(C=1N(C(=O)C2=CC=C(Cl)C=C2N=1)CC=1C=CC=CC=1)C(=O)N1CCOCC1 IFHLXHPKUGAEAO-UHFFFAOYSA-N 0.000 claims 1
- XKBPBVLWGXMACT-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-(3-benzyl-7-chloro-4-oxoquinazolin-2-yl)-2-oxo-2-pyrrolidin-1-ylethyl]-4-bromobenzamide Chemical compound C=1C=C(Br)C=CC=1C(=O)N(CCCN)C(C=1N(C(=O)C2=CC=C(Cl)C=C2N=1)CC=1C=CC=CC=1)C(=O)N1CCCC1 XKBPBVLWGXMACT-UHFFFAOYSA-N 0.000 claims 1
- RZCWDNXHRSULHO-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-(3-benzyl-7-chloro-4-oxoquinazolin-2-yl)-2-oxo-2-pyrrolidin-1-ylethyl]-4-chlorobenzamide Chemical compound C=1C=C(Cl)C=CC=1C(=O)N(CCCN)C(C=1N(C(=O)C2=CC=C(Cl)C=C2N=1)CC=1C=CC=CC=1)C(=O)N1CCCC1 RZCWDNXHRSULHO-UHFFFAOYSA-N 0.000 claims 1
- LOBHTHORIKJWKT-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-(3-benzyl-7-chloro-4-oxoquinazolin-2-yl)-2-oxo-2-pyrrolidin-1-ylethyl]-4-methylbenzamide Chemical compound C1=CC(C)=CC=C1C(=O)N(CCCN)C(C=1N(C(=O)C2=CC=C(Cl)C=C2N=1)CC=1C=CC=CC=1)C(=O)N1CCCC1 LOBHTHORIKJWKT-UHFFFAOYSA-N 0.000 claims 1
- ACBBOCDJQNMBMX-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-[7-chloro-3-(naphthalen-2-ylmethyl)-4-oxoquinazolin-2-yl]-2-(dimethylamino)-2-oxoethyl]-4-methylbenzamide Chemical compound N=1C2=CC(Cl)=CC=C2C(=O)N(CC=2C=C3C=CC=CC3=CC=2)C=1C(C(=O)N(C)C)N(CCCN)C(=O)C1=CC=C(C)C=C1 ACBBOCDJQNMBMX-UHFFFAOYSA-N 0.000 claims 1
- YAGKZVYRBNAUCT-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-[7-chloro-3-[(2-chloropyridin-4-yl)methyl]-4-oxoquinazolin-2-yl]-2-(dimethylamino)-2-oxoethyl]-4-methylbenzamide Chemical compound N=1C2=CC(Cl)=CC=C2C(=O)N(CC=2C=C(Cl)N=CC=2)C=1C(C(=O)N(C)C)N(CCCN)C(=O)C1=CC=C(C)C=C1 YAGKZVYRBNAUCT-UHFFFAOYSA-N 0.000 claims 1
- WCTPJXDMLTZVGB-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-[7-chloro-3-[(3-chlorophenyl)methyl]-4-oxoquinazolin-2-yl]-2-(dimethylamino)-2-oxoethyl]-4-methylbenzamide Chemical compound N=1C2=CC(Cl)=CC=C2C(=O)N(CC=2C=C(Cl)C=CC=2)C=1C(C(=O)N(C)C)N(CCCN)C(=O)C1=CC=C(C)C=C1 WCTPJXDMLTZVGB-UHFFFAOYSA-N 0.000 claims 1
- KCWAGPKXNHROMB-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-[7-chloro-3-[(3-cyanophenyl)methyl]-4-oxoquinazolin-2-yl]-2-(dimethylamino)-2-oxoethyl]-4-methylbenzamide Chemical compound N=1C2=CC(Cl)=CC=C2C(=O)N(CC=2C=C(C=CC=2)C#N)C=1C(C(=O)N(C)C)N(CCCN)C(=O)C1=CC=C(C)C=C1 KCWAGPKXNHROMB-UHFFFAOYSA-N 0.000 claims 1
- WTHOBWPGVADYCP-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-[7-chloro-3-[(3-fluorophenyl)methyl]-4-oxoquinazolin-2-yl]-2-(dimethylamino)-2-oxoethyl]-4-methylbenzamide Chemical compound N=1C2=CC(Cl)=CC=C2C(=O)N(CC=2C=C(F)C=CC=2)C=1C(C(=O)N(C)C)N(CCCN)C(=O)C1=CC=C(C)C=C1 WTHOBWPGVADYCP-UHFFFAOYSA-N 0.000 claims 1
- FXFKDKAQPMEUHH-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-[7-chloro-3-[(3-hydroxyphenyl)methyl]-4-oxoquinazolin-2-yl]-2-(dimethylamino)-2-oxoethyl]-4-methylbenzamide Chemical compound N=1C2=CC(Cl)=CC=C2C(=O)N(CC=2C=C(O)C=CC=2)C=1C(C(=O)N(C)C)N(CCCN)C(=O)C1=CC=C(C)C=C1 FXFKDKAQPMEUHH-UHFFFAOYSA-N 0.000 claims 1
- YUUZYHHMHDULOO-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-[7-chloro-3-[(3-methoxyphenyl)methyl]-4-oxoquinazolin-2-yl]-2-(dimethylamino)-2-oxoethyl]-4-methylbenzamide Chemical compound COC1=CC=CC(CN2C(C3=CC=C(Cl)C=C3N=C2C(N(CCCN)C(=O)C=2C=CC(C)=CC=2)C(=O)N(C)C)=O)=C1 YUUZYHHMHDULOO-UHFFFAOYSA-N 0.000 claims 1
- KKLQRJWUJNLWKR-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-[7-chloro-3-[(3-methoxyphenyl)methyl]-4-oxoquinazolin-2-yl]-2-[ethyl(methyl)amino]-2-oxoethyl]-4-methylbenzamide Chemical compound N=1C2=CC(Cl)=CC=C2C(=O)N(CC=2C=C(OC)C=CC=2)C=1C(C(=O)N(C)CC)N(CCCN)C(=O)C1=CC=C(C)C=C1 KKLQRJWUJNLWKR-UHFFFAOYSA-N 0.000 claims 1
- LFCFRWGOOZKXAB-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-[7-chloro-3-[(3-methylphenyl)methyl]-4-oxoquinazolin-2-yl]-2-(dimethylamino)-2-oxoethyl]-4-methylbenzamide Chemical compound N=1C2=CC(Cl)=CC=C2C(=O)N(CC=2C=C(C)C=CC=2)C=1C(C(=O)N(C)C)N(CCCN)C(=O)C1=CC=C(C)C=C1 LFCFRWGOOZKXAB-UHFFFAOYSA-N 0.000 claims 1
- BYCJSHLRPLZIRP-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-[7-chloro-3-[(4-chlorophenyl)methyl]-4-oxoquinazolin-2-yl]-2-(dimethylamino)-2-oxoethyl]-4-methylbenzamide Chemical compound N=1C2=CC(Cl)=CC=C2C(=O)N(CC=2C=CC(Cl)=CC=2)C=1C(C(=O)N(C)C)N(CCCN)C(=O)C1=CC=C(C)C=C1 BYCJSHLRPLZIRP-UHFFFAOYSA-N 0.000 claims 1
- QHSREIXXUCQSJB-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-[7-chloro-3-[(6-chloropyridin-2-yl)methyl]-4-oxoquinazolin-2-yl]-2-(dimethylamino)-2-oxoethyl]-4-methylbenzamide Chemical compound N=1C2=CC(Cl)=CC=C2C(=O)N(CC=2N=C(Cl)C=CC=2)C=1C(C(=O)N(C)C)N(CCCN)C(=O)C1=CC=C(C)C=C1 QHSREIXXUCQSJB-UHFFFAOYSA-N 0.000 claims 1
- TYOPSQBNGUCXIT-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-[7-chloro-4-oxo-3-[(3-phenylphenyl)methyl]quinazolin-2-yl]-2-(dimethylamino)-2-oxoethyl]-4-methylbenzamide Chemical compound N=1C2=CC(Cl)=CC=C2C(=O)N(CC=2C=C(C=CC=2)C=2C=CC=CC=2)C=1C(C(=O)N(C)C)N(CCCN)C(=O)C1=CC=C(C)C=C1 TYOPSQBNGUCXIT-UHFFFAOYSA-N 0.000 claims 1
- MMUBVVLHJMVNNI-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-[7-chloro-4-oxo-3-[[3-(trifluoromethoxy)phenyl]methyl]quinazolin-2-yl]-2-(dimethylamino)-2-oxoethyl]-4-methylbenzamide Chemical compound N=1C2=CC(Cl)=CC=C2C(=O)N(CC=2C=C(OC(F)(F)F)C=CC=2)C=1C(C(=O)N(C)C)N(CCCN)C(=O)C1=CC=C(C)C=C1 MMUBVVLHJMVNNI-UHFFFAOYSA-N 0.000 claims 1
- MSOLDLXOAIVCRD-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-[7-chloro-4-oxo-3-[[3-(trifluoromethyl)phenyl]methyl]quinazolin-2-yl]-2-(dimethylamino)-2-oxoethyl]-4-methylbenzamide Chemical compound N=1C2=CC(Cl)=CC=C2C(=O)N(CC=2C=C(C=CC=2)C(F)(F)F)C=1C(C(=O)N(C)C)N(CCCN)C(=O)C1=CC=C(C)C=C1 MSOLDLXOAIVCRD-UHFFFAOYSA-N 0.000 claims 1
- SZIUNCQWNWCERK-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-[7-chloro-4-oxo-3-[[4-(trifluoromethoxy)phenyl]methyl]quinazolin-2-yl]-2-(dimethylamino)-2-oxoethyl]-4-methylbenzamide Chemical compound N=1C2=CC(Cl)=CC=C2C(=O)N(CC=2C=CC(OC(F)(F)F)=CC=2)C=1C(C(=O)N(C)C)N(CCCN)C(=O)C1=CC=C(C)C=C1 SZIUNCQWNWCERK-UHFFFAOYSA-N 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 32
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 56
- 206010028980 Neoplasm Diseases 0.000 description 28
- 229910052799 carbon Inorganic materials 0.000 description 25
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
- 201000011510 cancer Diseases 0.000 description 20
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 19
- 210000004027 cell Anatomy 0.000 description 19
- 235000019439 ethyl acetate Nutrition 0.000 description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 17
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- 239000002904 solvent Substances 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 14
- 125000004432 carbon atom Chemical group C* 0.000 description 14
- 239000003112 inhibitor Substances 0.000 description 14
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/88—Oxygen atoms
- C07D239/90—Oxygen atoms with acyclic radicals attached in position 2 or 3
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| US52505903P | 2003-11-25 | 2003-11-25 | |
| US60/525,059 | 2003-11-25 | ||
| PCT/US2004/039448 WO2005051922A1 (en) | 2003-11-25 | 2004-11-24 | Quinazolinone compounds as anticancer agents |
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| JP2010285141A Division JP2011084570A (ja) | 2003-11-25 | 2010-12-21 | 抗癌剤としてのキナゾリノン化合物 |
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| EP (1) | EP1689724B1 (https=) |
| JP (2) | JP4778439B2 (https=) |
| KR (1) | KR20060127413A (https=) |
| CN (1) | CN1886384A (https=) |
| AT (1) | ATE538103T1 (https=) |
| AU (1) | AU2004293464A1 (https=) |
| CA (1) | CA2546932A1 (https=) |
| CY (1) | CY1112478T1 (https=) |
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| ES (1) | ES2376552T3 (https=) |
| IL (1) | IL175714A0 (https=) |
| PL (1) | PL1689724T3 (https=) |
| PT (1) | PT1689724E (https=) |
| SG (1) | SG148202A1 (https=) |
| SI (1) | SI1689724T1 (https=) |
| WO (1) | WO2005051922A1 (https=) |
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| US6545004B1 (en) * | 1999-10-27 | 2003-04-08 | Cytokinetics, Inc. | Methods and compositions utilizing quinazolinones |
| US7671200B2 (en) * | 1999-10-27 | 2010-03-02 | Cytokinetics, Inc. | Quinazolinone KSP inhibitors |
| US7230000B1 (en) * | 1999-10-27 | 2007-06-12 | Cytokinetics, Incorporated | Methods and compositions utilizing quinazolinones |
| JP2005529076A (ja) * | 2002-02-15 | 2005-09-29 | サイトキネティクス・インコーポレーテッド | キナゾリノンの合成 |
| EP1553931A4 (en) * | 2002-05-09 | 2006-08-30 | Cytokinetics Inc | COMPOUNDS, COMPOSITIONS AND METHODS |
| EP1513820A4 (en) | 2002-05-23 | 2006-09-13 | Cytokinetics Inc | COMPOUNDS, COMPOSITIONS AND METHODS |
| EP1537089A4 (en) | 2002-07-23 | 2008-04-16 | Cytokinetics Inc | CONNECTIONS, COMPOSITIONS AND PROCEDURES |
| WO2004034972A2 (en) * | 2002-09-30 | 2004-04-29 | Cytokinetics, Inc. | Compounds, compositions, and methods |
| NZ551004A (en) | 2004-04-02 | 2010-07-30 | Prana Biotechnology Ltd | Neurologically-active compounds |
| EP1781674A1 (en) | 2004-08-18 | 2007-05-09 | AstraZeneca AB | Enantiomers of selected fused pyrimidones and uses in the treatment and prevention of cancer |
| US20070207996A1 (en) * | 2004-08-30 | 2007-09-06 | Auger Kurt R | Novel Compositions And Methods Of Treatment |
| CA2584412C (en) * | 2004-09-14 | 2017-05-09 | Minerva Biotechnologies Corporation | Methods for diagnosis and treatment of cancer |
| CN101534824A (zh) | 2006-11-17 | 2009-09-16 | 艾博特公司 | 作为化学活素受体拮抗剂的氨基吡咯烷 |
| KR100916160B1 (ko) * | 2007-02-21 | 2009-09-08 | (주)바이오버드 | 약제학적 항암 조성물 |
| WO2009102537A1 (en) * | 2008-02-14 | 2009-08-20 | Merck & Co., Inc. | Inhibitors of checkpoint kinases |
| CN101250189B (zh) * | 2008-03-25 | 2010-06-16 | 中山大学 | 双脂肪氨基取代喹唑酮衍生物及其制备方法与作为抗癌药物的应用 |
| US8440693B2 (en) | 2009-12-22 | 2013-05-14 | Novartis Ag | Substituted isoquinolinones and quinazolinones |
| CN101857595B (zh) * | 2010-05-21 | 2012-11-21 | 中山大学 | 一种喹唑酮衍生物及其制备方法和作为抗癌药物的用途 |
| CN101899009B (zh) * | 2010-07-30 | 2012-04-04 | 江苏昊华精细化工有限公司 | 医药中间体4(h)喹唑酮的制造方法 |
| CN101967127B (zh) * | 2010-09-28 | 2013-05-29 | 中山大学 | 一种喹唑啉衍生物及其制备方法和制备抗癌药物中的应用 |
| DE102012101680A1 (de) * | 2012-02-29 | 2013-08-29 | Aicuris Gmbh & Co. Kg | Pharmazeutische Zubereitung enthaltend ein antiviral wirksames Dihydrochinazolinderivat |
| US8940742B2 (en) | 2012-04-10 | 2015-01-27 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| EP2855483B1 (en) | 2012-05-24 | 2017-10-25 | Novartis AG | Pyrrolopyrrolidinone compounds |
| CN103012291B (zh) * | 2012-12-17 | 2014-09-03 | 中山大学 | 一种2-苯基喹唑啉衍生物及其制备方法与在制备抗癌药物中的应用 |
| AU2013364068B2 (en) | 2012-12-21 | 2016-10-20 | Gilead Calistoga Llc | Substituted pyrimidine aminoalkyl-quinazolones as phosphatidylinositol 3-kinase inhibitors |
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- 2004-11-24 WO PCT/US2004/039448 patent/WO2005051922A1/en not_active Ceased
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- 2004-11-24 CN CNA2004800348103A patent/CN1886384A/zh active Pending
- 2004-11-24 JP JP2006541684A patent/JP4778439B2/ja not_active Expired - Fee Related
- 2004-11-24 DK DK04812051.3T patent/DK1689724T3/da active
- 2004-11-24 ES ES04812051T patent/ES2376552T3/es not_active Expired - Lifetime
- 2004-11-24 SG SG200808730-6A patent/SG148202A1/en unknown
- 2004-11-24 AU AU2004293464A patent/AU2004293464A1/en not_active Abandoned
- 2004-11-24 AT AT04812051T patent/ATE538103T1/de active
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- 2004-11-24 CA CA002546932A patent/CA2546932A1/en not_active Abandoned
- 2004-11-24 PL PL04812051T patent/PL1689724T3/pl unknown
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|---|---|
| CA2546932A1 (en) | 2005-06-09 |
| EP1689724A1 (en) | 2006-08-16 |
| PT1689724E (pt) | 2012-02-06 |
| KR20060127413A (ko) | 2006-12-12 |
| DK1689724T3 (da) | 2012-02-27 |
| US20110190293A1 (en) | 2011-08-04 |
| US20050209254A1 (en) | 2005-09-22 |
| EP1689724B1 (en) | 2011-12-21 |
| US7939539B2 (en) | 2011-05-10 |
| ATE538103T1 (de) | 2012-01-15 |
| PL1689724T3 (pl) | 2012-05-31 |
| ES2376552T3 (es) | 2012-03-14 |
| SG148202A1 (en) | 2008-12-31 |
| WO2005051922A1 (en) | 2005-06-09 |
| JP2007512368A (ja) | 2007-05-17 |
| IL175714A0 (en) | 2006-09-05 |
| SI1689724T1 (sl) | 2012-04-30 |
| JP2011084570A (ja) | 2011-04-28 |
| CY1112478T1 (el) | 2015-12-09 |
| CN1886384A (zh) | 2006-12-27 |
| AU2004293464A1 (en) | 2005-06-09 |
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