JP2006514991A - 新規医薬組合せ - Google Patents
新規医薬組合せ Download PDFInfo
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- JP2006514991A JP2006514991A JP2005509699A JP2005509699A JP2006514991A JP 2006514991 A JP2006514991 A JP 2006514991A JP 2005509699 A JP2005509699 A JP 2005509699A JP 2005509699 A JP2005509699 A JP 2005509699A JP 2006514991 A JP2006514991 A JP 2006514991A
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- 150000001875 compounds Chemical class 0.000 claims abstract description 385
- 201000010099 disease Diseases 0.000 claims abstract description 38
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 38
- 230000003388 anti-hormonal effect Effects 0.000 claims abstract description 26
- 238000011282 treatment Methods 0.000 claims abstract description 23
- 230000033115 angiogenesis Effects 0.000 claims abstract description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 501
- -1 cyano, carboxy Chemical group 0.000 claims description 181
- ZYHQGITXIJDDKC-UHFFFAOYSA-N 2-[2-(2-aminophenyl)ethyl]aniline Chemical group NC1=CC=CC=C1CCC1=CC=CC=C1N ZYHQGITXIJDDKC-UHFFFAOYSA-N 0.000 claims description 169
- 125000004432 carbon atom Chemical group C* 0.000 claims description 88
- 125000000217 alkyl group Chemical group 0.000 claims description 71
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 71
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 63
- 125000003282 alkyl amino group Chemical group 0.000 claims description 60
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 54
- 150000003839 salts Chemical class 0.000 claims description 49
- 229910052736 halogen Inorganic materials 0.000 claims description 48
- 150000002367 halogens Chemical class 0.000 claims description 47
- 125000001424 substituent group Chemical group 0.000 claims description 45
- 229910052757 nitrogen Inorganic materials 0.000 claims description 41
- 125000003545 alkoxy group Chemical group 0.000 claims description 40
- 238000002360 preparation method Methods 0.000 claims description 40
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 38
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 claims description 38
- 125000002947 alkylene group Chemical group 0.000 claims description 32
- 125000000623 heterocyclic group Chemical group 0.000 claims description 32
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 30
- 125000004076 pyridyl group Chemical group 0.000 claims description 30
- 125000003277 amino group Chemical group 0.000 claims description 29
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 28
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 28
- 125000004414 alkyl thio group Chemical group 0.000 claims description 25
- 125000001589 carboacyl group Chemical group 0.000 claims description 24
- 206010028980 Neoplasm Diseases 0.000 claims description 21
- 241000534944 Thia Species 0.000 claims description 21
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 21
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 20
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 20
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 19
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 19
- 230000005764 inhibitory process Effects 0.000 claims description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 229960001603 tamoxifen Drugs 0.000 claims description 18
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 15
- INVTYAOGFAGBOE-UHFFFAOYSA-N entinostat Chemical compound NC1=CC=CC=C1NC(=O)C(C=C1)=CC=C1CNC(=O)OCC1=CC=CN=C1 INVTYAOGFAGBOE-UHFFFAOYSA-N 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 13
- 125000004122 cyclic group Chemical group 0.000 claims description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
- 230000001225 therapeutic effect Effects 0.000 claims description 11
- SHGAZHPCJJPHSC-NUEINMDLSA-N Isotretinoin Chemical compound OC(=O)C=C(C)/C=C/C=C(C)C=CC1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-NUEINMDLSA-N 0.000 claims description 10
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 claims description 10
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 10
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 10
- 230000002280 anti-androgenic effect Effects 0.000 claims description 9
- 230000001833 anti-estrogenic effect Effects 0.000 claims description 9
- 239000000328 estrogen antagonist Substances 0.000 claims description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
- 230000003623 progesteronic effect Effects 0.000 claims description 9
- 241001465754 Metazoa Species 0.000 claims description 8
- 125000002252 acyl group Chemical group 0.000 claims description 8
- 125000004423 acyloxy group Chemical group 0.000 claims description 8
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- SHGAZHPCJJPHSC-ZVCIMWCZSA-N 9-cis-retinoic acid Chemical compound OC(=O)/C=C(\C)/C=C/C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-ZVCIMWCZSA-N 0.000 claims description 7
- 229960001445 alitretinoin Drugs 0.000 claims description 7
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 7
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 7
- 229940046836 anti-estrogen Drugs 0.000 claims description 7
- 239000000051 antiandrogen Substances 0.000 claims description 7
- 125000004429 atom Chemical group 0.000 claims description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 239000001301 oxygen Substances 0.000 claims description 7
- 239000000370 acceptor Substances 0.000 claims description 6
- 125000004442 acylamino group Chemical group 0.000 claims description 6
- 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 claims description 6
- 201000011510 cancer Diseases 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 6
- 230000014399 negative regulation of angiogenesis Effects 0.000 claims description 6
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 6
- 125000003107 substituted aryl group Chemical group 0.000 claims description 6
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 206010016654 Fibrosis Diseases 0.000 claims description 5
- 108091008605 VEGF receptors Proteins 0.000 claims description 5
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 5
- 150000002391 heterocyclic compounds Chemical class 0.000 claims description 5
- 230000003211 malignant effect Effects 0.000 claims description 5
- BDKWVFXIGVUEGA-UHFFFAOYSA-N n-(4-chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine;hydrochloride Chemical compound Cl.C1=CC(Cl)=CC=C1NC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 BDKWVFXIGVUEGA-UHFFFAOYSA-N 0.000 claims description 5
- 125000004304 oxazol-5-yl group Chemical group O1C=NC=C1* 0.000 claims description 5
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 5
- 125000004434 sulfur atom Chemical group 0.000 claims description 5
- 210000005166 vasculature Anatomy 0.000 claims description 5
- IEXUMDBQLIVNHZ-YOUGDJEHSA-N (8s,11r,13r,14s,17s)-11-[4-(dimethylamino)phenyl]-17-hydroxy-17-(3-hydroxypropyl)-13-methyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-one Chemical compound C1=CC(N(C)C)=CC=C1[C@@H]1C2=C3CCC(=O)C=C3CC[C@H]2[C@H](CC[C@]2(O)CCCO)[C@@]2(C)C1 IEXUMDBQLIVNHZ-YOUGDJEHSA-N 0.000 claims description 4
- UIOAQJNADLELPQ-UHFFFAOYSA-N C[C]1OCCO1 Chemical group C[C]1OCCO1 UIOAQJNADLELPQ-UHFFFAOYSA-N 0.000 claims description 4
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 4
- 239000003418 antiprogestin Substances 0.000 claims description 4
- UWFYSQMTEOIJJG-FDTZYFLXSA-N cyproterone acetate Chemical compound C1=C(Cl)C2=CC(=O)[C@@H]3C[C@@H]3[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 UWFYSQMTEOIJJG-FDTZYFLXSA-N 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 claims description 4
- 210000000944 nerve tissue Anatomy 0.000 claims description 4
- 229950011093 onapristone Drugs 0.000 claims description 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 4
- 230000000451 tissue damage Effects 0.000 claims description 4
- 231100000827 tissue damage Toxicity 0.000 claims description 4
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 claims description 4
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 3
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 claims description 3
- ZSNZPFYMIVNIMW-UHFFFAOYSA-N 3-[[4-(pyridin-4-ylmethyl)phthalazin-1-yl]amino]phenol Chemical compound OC1=CC=CC(NC=2C3=CC=CC=C3C(CC=3C=CN=CC=3)=NN=2)=C1 ZSNZPFYMIVNIMW-UHFFFAOYSA-N 0.000 claims description 3
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 3
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 3
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 3
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims description 3
- RJTXGOMLCHEWDN-UHFFFAOYSA-N 3-n-[4-(pyridin-4-ylmethyl)phthalazin-1-yl]benzene-1,3-diamine Chemical compound NC1=CC=CC(NC=2C3=CC=CC=C3C(CC=3C=CN=CC=3)=NN=2)=C1 RJTXGOMLCHEWDN-UHFFFAOYSA-N 0.000 claims description 3
- UECARSVRLSHXNH-UHFFFAOYSA-N 4-(pyridin-4-ylmethyl)-n-[4-(trifluoromethyl)phenyl]phthalazin-1-amine Chemical compound C1=CC(C(F)(F)F)=CC=C1NC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 UECARSVRLSHXNH-UHFFFAOYSA-N 0.000 claims description 3
- ZYBSZFIPVRRAOR-UHFFFAOYSA-N 4-[[4-(pyridin-4-ylmethyl)phthalazin-1-yl]amino]benzonitrile Chemical compound C1=CC(C#N)=CC=C1NC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 ZYBSZFIPVRRAOR-UHFFFAOYSA-N 0.000 claims description 3
- WQADYQNSWQTHBP-UHFFFAOYSA-N 4-[[4-(pyridin-4-ylmethyl)phthalazin-1-yl]amino]phenol Chemical compound C1=CC(O)=CC=C1NC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 WQADYQNSWQTHBP-UHFFFAOYSA-N 0.000 claims description 3
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 3
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical group CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims description 3
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 3
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 3
- 208000010412 Glaucoma Diseases 0.000 claims description 3
- 206010018364 Glomerulonephritis Diseases 0.000 claims description 3
- 206010030113 Oedema Diseases 0.000 claims description 3
- 230000007882 cirrhosis Effects 0.000 claims description 3
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 3
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims description 3
- 208000033679 diabetic kidney disease Diseases 0.000 claims description 3
- 230000001434 glomerular Effects 0.000 claims description 3
- 201000011066 hemangioma Diseases 0.000 claims description 3
- 229960005280 isotretinoin Drugs 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- SVAROSTUIFRLMR-UHFFFAOYSA-N n-(2-methoxyphenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine Chemical compound COC1=CC=CC=C1NC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 SVAROSTUIFRLMR-UHFFFAOYSA-N 0.000 claims description 3
- UIFQBRNVJVUAKO-UHFFFAOYSA-N n-(3,4-dichlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine Chemical compound C1=C(Cl)C(Cl)=CC=C1NC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 UIFQBRNVJVUAKO-UHFFFAOYSA-N 0.000 claims description 3
- KXGQVPDIEXTECH-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 KXGQVPDIEXTECH-UHFFFAOYSA-N 0.000 claims description 3
- AZIKUFVQGGFYBF-UHFFFAOYSA-N n-(3-chloro-4-methoxyphenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine Chemical compound C1=C(Cl)C(OC)=CC=C1NC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 AZIKUFVQGGFYBF-UHFFFAOYSA-N 0.000 claims description 3
- QSBVFBSIEWYFOV-UHFFFAOYSA-N n-(3-chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine Chemical compound ClC1=CC=CC(NC=2C3=CC=CC=C3C(CC=3C=CN=CC=3)=NN=2)=C1 QSBVFBSIEWYFOV-UHFFFAOYSA-N 0.000 claims description 3
- UHSUYVQDJJMDAA-UHFFFAOYSA-N n-(3-methoxyphenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine Chemical compound COC1=CC=CC(NC=2C3=CC=CC=C3C(CC=3C=CN=CC=3)=NN=2)=C1 UHSUYVQDJJMDAA-UHFFFAOYSA-N 0.000 claims description 3
- UTBZTQCKLUFYTQ-UHFFFAOYSA-N n-(3-methylphenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine Chemical compound CC1=CC=CC(NC=2C3=CC=CC=C3C(CC=3C=CN=CC=3)=NN=2)=C1 UTBZTQCKLUFYTQ-UHFFFAOYSA-N 0.000 claims description 3
- OHJRTXSBHFKDQN-UHFFFAOYSA-N n-(3-phenylmethoxyphenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine Chemical compound C=1C=CC=CC=1COC(C=1)=CC=CC=1NC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 OHJRTXSBHFKDQN-UHFFFAOYSA-N 0.000 claims description 3
- YSCVOKMJKSNAMT-UHFFFAOYSA-N n-(4-bromophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine Chemical compound C1=CC(Br)=CC=C1NC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 YSCVOKMJKSNAMT-UHFFFAOYSA-N 0.000 claims description 3
- FAYDFKSMRTYYNR-UHFFFAOYSA-N n-(4-fluorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine Chemical compound C1=CC(F)=CC=C1NC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 FAYDFKSMRTYYNR-UHFFFAOYSA-N 0.000 claims description 3
- SJDGLBJMCUMNTP-UHFFFAOYSA-N n-(4-methoxyphenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine Chemical compound C1=CC(OC)=CC=C1NC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 SJDGLBJMCUMNTP-UHFFFAOYSA-N 0.000 claims description 3
- XPCHMPWXUOYJGJ-UHFFFAOYSA-N n-(4-methylphenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine Chemical compound C1=CC(C)=CC=C1NC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 XPCHMPWXUOYJGJ-UHFFFAOYSA-N 0.000 claims description 3
- FOZIFOSSSDWNSN-UHFFFAOYSA-N n-benzyl-4-(pyridin-4-ylmethyl)phthalazin-1-amine Chemical compound C=1C=CC=CC=1CNC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 FOZIFOSSSDWNSN-UHFFFAOYSA-N 0.000 claims description 3
- WFPYLUYNQSOURF-UHFFFAOYSA-N n-phenyl-4-(pyridin-4-ylmethyl)phthalazin-1-amine Chemical compound N=1N=C(NC=2C=CC=CC=2)C2=CC=CC=C2C=1CC1=CC=NC=C1 WFPYLUYNQSOURF-UHFFFAOYSA-N 0.000 claims description 3
- 201000003142 neovascular glaucoma Diseases 0.000 claims description 3
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- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 3
- 230000002062 proliferating effect Effects 0.000 claims description 3
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- YCOYDOIWSSHVCK-UHFFFAOYSA-N vatalanib Chemical compound C1=CC(Cl)=CC=C1NC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 YCOYDOIWSSHVCK-UHFFFAOYSA-N 0.000 claims description 3
- ZPTFNZILFJJXGC-XOKGGSDKSA-N (1S,2S,3S,5R,11R,12S,15R,16S)-15-acetyl-7,9-dichloro-15-hydroxy-2,16-dimethylpentacyclo[9.7.0.02,8.03,5.012,16]octadeca-7,9-dien-6-one Chemical compound C1=C(Cl)C2=C(Cl)C(=O)[C@@H]3C[C@@H]3[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)C)(O)[C@@]1(C)CC2 ZPTFNZILFJJXGC-XOKGGSDKSA-N 0.000 claims description 2
- RSPINGMAWKOXBT-BZGHQHJYSA-N (8r,9s,13s,14s,16s,17s)-16-ethyl-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol Chemical compound C1CC2=CC(O)=CC=C2[C@@H]2[C@@H]1[C@@H]1C[C@H](CC)[C@H](O)[C@@]1(C)CC2 RSPINGMAWKOXBT-BZGHQHJYSA-N 0.000 claims description 2
- HJOOGTROABIIIU-UHFFFAOYSA-N 1-[2-[4-(6-methoxy-2-phenyl-3,4-dihydronaphthalen-1-yl)phenoxy]ethyl]pyrrolidine;hydrochloride Chemical compound Cl.C1CC2=CC(OC)=CC=C2C(C=2C=CC(OCCN3CCCC3)=CC=2)=C1C1=CC=CC=C1 HJOOGTROABIIIU-UHFFFAOYSA-N 0.000 claims description 2
- SQAORNVRAYTOMS-UHFFFAOYSA-N 2-methyl-4-[4-nitro-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazinan-3-one Chemical compound O=C1N(C)OCCN1C1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 SQAORNVRAYTOMS-UHFFFAOYSA-N 0.000 claims description 2
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 2
- WQKHERPPDYPMNX-UHFFFAOYSA-N 6-chloro-3,4-dihydro-2h-naphthalen-1-one Chemical compound O=C1CCCC2=CC(Cl)=CC=C21 WQKHERPPDYPMNX-UHFFFAOYSA-N 0.000 claims description 2
- DQRBQYWUILSPIG-UHFFFAOYSA-N 8-amino-5-hydroxy-4-iminonaphthalen-1-one Chemical compound C1(=N)C2=C(O)C=CC(N)=C2C(=O)C=C1 DQRBQYWUILSPIG-UHFFFAOYSA-N 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
- 208000003120 Angiofibroma Diseases 0.000 claims description 2
- 201000001320 Atherosclerosis Diseases 0.000 claims description 2
- QMBJSIBWORFWQT-DFXBJWIESA-N Chlormadinone acetate Chemical compound C1=C(Cl)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 QMBJSIBWORFWQT-DFXBJWIESA-N 0.000 claims description 2
- KDYQVUUCWUPJGE-UHFFFAOYSA-N Ethamoxytriphetol Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(O)(C=1C=CC=CC=1)CC1=CC=C(OC)C=C1 KDYQVUUCWUPJGE-UHFFFAOYSA-N 0.000 claims description 2
- QCOGKXLOEWLIDC-UHFFFAOYSA-N N-methylbutylamine Chemical compound CCCCNC QCOGKXLOEWLIDC-UHFFFAOYSA-N 0.000 claims description 2
- 206010038563 Reocclusion Diseases 0.000 claims description 2
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| EP1429765A2 (en) | 2001-09-14 | 2004-06-23 | Methylgene, Inc. | Inhibitors of histone deacetylase |
| US7868204B2 (en) | 2001-09-14 | 2011-01-11 | Methylgene Inc. | Inhibitors of histone deacetylase |
| CA2531485C (en) * | 2003-07-07 | 2013-03-26 | Merck Patent Gmbh | Malonamide derivatives |
| KR101153335B1 (ko) | 2003-09-24 | 2012-07-05 | 메틸진 인코포레이티드 | 히스톤 데아세틸라제의 억제제 |
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| JP2008524246A (ja) * | 2004-12-16 | 2008-07-10 | タケダ サン ディエゴ インコーポレイテッド | ヒストンデアセチラーゼ阻害剤 |
| AU2006240246A1 (en) | 2005-04-20 | 2006-11-02 | Merck Sharp & Dohme Corp. | Benzothiophene hydroxamic acid derivatives with carbamate, urea, amide and sulfonamide substitutions |
| CA2605110A1 (en) | 2005-04-20 | 2006-11-02 | Merck & Co., Inc. | Benzothiophene derivatives |
| AU2006240248A1 (en) | 2005-04-20 | 2006-11-02 | Merck Sharp & Dohme Corp. | Benzothiophene hydroxamic acid derivatives |
| US7642253B2 (en) | 2005-05-11 | 2010-01-05 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
| JP2008546793A (ja) | 2005-06-24 | 2008-12-25 | メルク エンド カムパニー インコーポレーテッド | 修飾マロン酸誘導体 |
| EA200800321A1 (ru) * | 2005-07-14 | 2008-06-30 | Такеда Сан Диего, Инк. | Ингибиторы гистондеацетилазы |
| AR057579A1 (es) | 2005-11-23 | 2007-12-05 | Merck & Co Inc | Compuestos espirociclicos como inhibidores de histona de acetilasa (hdac) |
| JP2009120486A (ja) * | 2005-12-05 | 2009-06-04 | Mitsubishi Pharma Corp | 核内オーファン受容体の新規活性化剤及びその用途 |
| JP2009528354A (ja) | 2006-02-28 | 2009-08-06 | メルク エンド カムパニー インコーポレーテッド | ヒストン脱アセチル化酵素のインヒビター |
| KR101495611B1 (ko) | 2006-04-07 | 2015-02-25 | 메틸진 인코포레이티드 | 히스톤 데아세틸라아제의 억제제 |
| CA2649861A1 (en) | 2006-04-26 | 2007-11-08 | Merck & Co., Inc. | Disubstituted aniline compounds |
| CA2651681A1 (en) | 2006-05-18 | 2007-11-29 | Merck & Co., Inc. | Aryl-fused spirocyclic compounds |
| EP2049124A4 (en) | 2006-07-20 | 2010-02-10 | Merck & Co Inc | PHOSPHOR DERIVATIVES AS HISTONDEACETYLASE HEMMER |
| WO2009005638A2 (en) | 2007-06-27 | 2009-01-08 | Merck & Co., Inc. | Pyridyl and pyrimidinyl derivatives as histone deacetylase inhibitors |
| EP3103791B1 (en) | 2007-06-27 | 2018-01-31 | Merck Sharp & Dohme Corp. | 4-carboxybenzylamino derivatives as histone deacetylase inhibitors |
| EP2060565A1 (en) | 2007-11-16 | 2009-05-20 | 4Sc Ag | Novel bifunctional compounds which inhibit protein kinases and histone deacetylases |
| EP2330894B8 (en) | 2008-09-03 | 2017-04-19 | BioMarin Pharmaceutical Inc. | Compositions including 6-aminohexanoic acid derivatives as hdac inhibitors |
| US8716326B2 (en) * | 2009-05-15 | 2014-05-06 | Korea Research Institute Of Chemical Technology | Isoindolinone derivatives, preparation method thereof and a pharmaceutical composition comprising same |
| US8912184B1 (en) | 2010-03-01 | 2014-12-16 | Alzheimer's Institute Of America, Inc. | Therapeutic and diagnostic methods |
| US10059723B2 (en) | 2011-02-28 | 2018-08-28 | Biomarin Pharmaceutical Inc. | Histone deacetylase inhibitors |
| US9540395B2 (en) | 2011-02-28 | 2017-01-10 | Biomarin Pharmaceutical Inc. | Histone deacetylase inhibitors |
| US8957066B2 (en) | 2011-02-28 | 2015-02-17 | Biomarin Pharmaceutical Inc. | Histone deacetylase inhibitors |
| WO2014160221A1 (en) | 2013-03-13 | 2014-10-02 | The General Hospital Corporation | Photoswitchable hdac inhibitors |
| WO2014143666A1 (en) | 2013-03-15 | 2014-09-18 | Biomarin Pharmaceutical Inc. | Hdac inhibitors |
| TWI635077B (zh) * | 2016-08-11 | 2018-09-11 | 行政院原子能委員會核能研究所 | 針對腫瘤診斷與治療之組織蛋白去乙醯酶抑制劑（ＨＤＡＣｉ）ＰＥＴ造影化合物與類似物，及其製造方法 |
| US11208382B2 (en) * | 2017-07-28 | 2021-12-28 | Hangzhou Solipharma Co., Ltd. | Entinostat-containing compound, crystal form of compound thereof, and preparation method therefor and pharmaceutical composition thereof |
| KR102831570B1 (ko) | 2018-05-04 | 2025-07-10 | 레미디 플랜, 인크. | 암 줄기 세포를 표적화하는 암 치료 |
| EP3982968A4 (en) * | 2019-06-13 | 2023-07-05 | Dana-Farber Cancer Institute, Inc. | DEVELOPMENT OF HDAC3 CATALYTIC INHIBITOR AND USES THEREOF |
| CN114957132A (zh) * | 2021-02-20 | 2022-08-30 | 中国科学院上海药物研究所 | 含s构型的氨基苯甲酰胺基哒嗪酮类化合物、其制备方法、药物组合物及应用 |
| CN113200908B (zh) * | 2021-04-09 | 2022-07-19 | 南华大学 | 一种含叔胺的邻氨基苯甲酰胺类化合物及其制备与应用 |
| CN115703736B (zh) * | 2021-08-04 | 2025-05-16 | 中国海洋大学 | 靶向于hdac和nad合成的多靶点抑制剂及其用途 |
| KR102743956B1 (ko) * | 2021-10-08 | 2024-12-17 | 아주대학교산학협력단 | 히스톤 탈아세틸화효소 억제제를 포함하는 대사성 질환의 예방, 개선 또는 치료용 조성물 |
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| AU555658B2 (en) | 1981-04-03 | 1986-10-02 | Eli Lilly And Company | Benzothiophene compounds |
| DE3121152A1 (de) | 1981-05-22 | 1982-12-09 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | "verwendung der kombination eines aromatase-hemmers mit einem antiandrogen zur prophylaxe und therapie der prostatahyperplasie" |
| US5053405A (en) | 1990-06-21 | 1991-10-01 | Sterling Drug Inc. | Antiandrogenic sulfonylsteroidothiazoles |
| SE9300971D0 (sv) * | 1993-03-24 | 1993-03-24 | Jan Wadstein | Hudvaardskomposition |
| US6174905B1 (en) * | 1996-09-30 | 2001-01-16 | Mitsui Chemicals, Inc. | Cell differentiation inducer |
| CO4950519A1 (es) * | 1997-02-13 | 2000-09-01 | Novartis Ag | Ftalazinas, preparaciones farmaceuticas que las comprenden y proceso para su preparacion |
| GB0111078D0 (en) * | 2001-05-04 | 2001-06-27 | Novartis Ag | Organic compounds |
| DE60231068D1 (de) * | 2001-09-12 | 2009-03-19 | Novartis Ag | Die Verwendung von 4-Pyridylmethylphthalazinen zur Behandlung von Nierentumoren |
| JP4130179B2 (ja) * | 2001-09-27 | 2008-08-06 | ノバルティス アクチエンゲゼルシャフト | 骨髄腫を処置するためのｃ−ｋｉｔ阻害剤の使用 |
| MXPA04005561A (es) * | 2001-12-21 | 2004-12-06 | Bayer Pharmaceuticals Corp | Terapias de combinacion anti-angiogenesis que comprenden derivados de piridazina o piridina. |
-
2003
- 2003-12-11 AU AU2003292888A patent/AU2003292888A1/en not_active Abandoned
- 2003-12-11 EP EP03782372A patent/EP1641458A2/en not_active Withdrawn
- 2003-12-11 WO PCT/EP2003/014071 patent/WO2004058234A2/en not_active Ceased
- 2003-12-11 EP EP06090154A patent/EP1738752A1/en not_active Withdrawn
- 2003-12-11 JP JP2005509699A patent/JP2006514991A/ja active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2023524230A (ja) * | 2020-04-30 | 2023-06-09 | グレート ノベル セラピューティクス バイオテック アンド メディカルズ コーポレイション | 腫瘍微小環境における免疫調節のためのヒストンデアセチラーゼ阻害剤 |
| JP7748392B2 (ja) | 2020-04-30 | 2025-10-02 | グレート ノベル セラピューティクス バイオテック アンド メディカルズ コーポレイション | 腫瘍微小環境における免疫調節のためのヒストンデアセチラーゼ阻害剤 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1641458A2 (en) | 2006-04-05 |
| AU2003292888A1 (en) | 2004-07-22 |
| WO2004058234A2 (en) | 2004-07-15 |
| EP1738752A1 (en) | 2007-01-03 |
| WO2004058234A3 (en) | 2006-01-12 |
| AU2003292888A8 (en) | 2004-07-22 |
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