KR20080034436A - 암 치료에 사용되는 티아졸 유도체 및 유사체 - Google Patents
암 치료에 사용되는 티아졸 유도체 및 유사체 Download PDFInfo
- Publication number
- KR20080034436A KR20080034436A KR1020087001174A KR20087001174A KR20080034436A KR 20080034436 A KR20080034436 A KR 20080034436A KR 1020087001174 A KR1020087001174 A KR 1020087001174A KR 20087001174 A KR20087001174 A KR 20087001174A KR 20080034436 A KR20080034436 A KR 20080034436A
- Authority
- KR
- South Korea
- Prior art keywords
- compound
- formula
- benzyl
- alkyl
- trifluoromethyl
- 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.)
- Withdrawn
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- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 70
- 201000011510 cancer Diseases 0.000 title claims abstract description 49
- 150000007979 thiazole derivatives Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 428
- 238000011282 treatment Methods 0.000 claims abstract description 24
- 239000003814 drug Substances 0.000 claims abstract description 14
- 238000004519 manufacturing process Methods 0.000 claims abstract description 7
- -1 heterosilyl Chemical group 0.000 claims description 115
- 238000000034 method Methods 0.000 claims description 102
- 125000000217 alkyl group Chemical group 0.000 claims description 76
- 125000003118 aryl group Chemical group 0.000 claims description 50
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 37
- 125000001072 heteroaryl group Chemical group 0.000 claims description 29
- 239000002904 solvent Substances 0.000 claims description 29
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 28
- 125000005843 halogen group Chemical group 0.000 claims description 25
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 20
- 239000001257 hydrogen Substances 0.000 claims description 19
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 17
- 206010006187 Breast cancer Diseases 0.000 claims description 15
- 208000026310 Breast neoplasm Diseases 0.000 claims description 15
- 239000002671 adjuvant Substances 0.000 claims description 12
- 239000003085 diluting agent Substances 0.000 claims description 11
- 125000000623 heterocyclic group Chemical group 0.000 claims description 9
- 229940124597 therapeutic agent Drugs 0.000 claims description 9
- 206010060862 Prostate cancer Diseases 0.000 claims description 7
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- MGJFLAHLODASKL-UHFFFAOYSA-N 2-(4-chloroanilino)-5-[[3-(trifluoromethyl)phenyl]methyl]-1,3-thiazol-4-one Chemical compound FC(F)(F)C1=CC=CC(CC2C(N=C(NC=3C=CC(Cl)=CC=3)S2)=O)=C1 MGJFLAHLODASKL-UHFFFAOYSA-N 0.000 claims description 6
- 125000002541 furyl group Chemical group 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 239000000969 carrier Substances 0.000 claims description 5
- LKJFEVJLZCHMNR-UHFFFAOYSA-N 2-(4-methylanilino)-5-[[3-(trifluoromethyl)phenyl]methyl]-1,3-thiazol-4-one Chemical compound C1=CC(C)=CC=C1NC(S1)=NC(=O)C1CC1=CC=CC(C(F)(F)F)=C1 LKJFEVJLZCHMNR-UHFFFAOYSA-N 0.000 claims description 4
- 206010009944 Colon cancer Diseases 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 208000029742 colonic neoplasm Diseases 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- XCZIHERGIOEZRO-UHFFFAOYSA-N 2-(3,4-dichloroanilino)-5-[[3-(trifluoromethyl)phenyl]methyl]-1,3-thiazol-4-one Chemical compound FC(F)(F)C1=CC=CC(CC2C(NC(S2)=NC=2C=C(Cl)C(Cl)=CC=2)=O)=C1 XCZIHERGIOEZRO-UHFFFAOYSA-N 0.000 claims description 3
- OIGKPCHWEPMWOD-UHFFFAOYSA-N 2-(4-methylanilino)-5-(2-phenylethyl)-1,3-thiazol-4-one Chemical compound C1=CC(C)=CC=C1N=C1SC(CCC=2C=CC=CC=2)C(=O)N1 OIGKPCHWEPMWOD-UHFFFAOYSA-N 0.000 claims description 3
- OJOXIPILLXOGHW-UHFFFAOYSA-N 5-[(4-fluorophenyl)methyl]-2-(pyridin-2-ylamino)-1,3-thiazol-4-one Chemical compound C1=CC(F)=CC=C1CC1C(=O)N=C(NC=2N=CC=CC=2)S1 OJOXIPILLXOGHW-UHFFFAOYSA-N 0.000 claims description 3
- 239000012453 solvate Substances 0.000 claims description 3
- MEEOKGMAKDGKDE-UHFFFAOYSA-N 2-(2,4-dichloroanilino)-5-[[3-(trifluoromethyl)phenyl]methyl]-1,3-thiazol-4-one Chemical compound FC(F)(F)C1=CC=CC(CC2C(NC(S2)=NC=2C(=CC(Cl)=CC=2)Cl)=O)=C1 MEEOKGMAKDGKDE-UHFFFAOYSA-N 0.000 claims description 2
- LCBASURTTNEAPL-UHFFFAOYSA-N 2-(4-chloroanilino)-5-[(4-methylphenyl)methyl]-1,3-thiazol-4-one Chemical compound C1=CC(C)=CC=C1CC1C(=O)N=C(NC=2C=CC(Cl)=CC=2)S1 LCBASURTTNEAPL-UHFFFAOYSA-N 0.000 claims description 2
- CYCZYGRIZJUNBZ-UHFFFAOYSA-N 2-(4-methoxyanilino)-5-[[3-(trifluoromethyl)phenyl]methyl]-1,3-thiazol-4-one Chemical compound C1=CC(OC)=CC=C1N=C1SC(CC=2C=C(C=CC=2)C(F)(F)F)C(=O)N1 CYCZYGRIZJUNBZ-UHFFFAOYSA-N 0.000 claims description 2
- ACQMGTBEKGXGJU-UHFFFAOYSA-N 2-(4-propan-2-ylanilino)-5-[[3-(trifluoromethyl)phenyl]methyl]-1,3-thiazol-4-one Chemical compound C1=CC(C(C)C)=CC=C1N=C1SC(CC=2C=C(C=CC=2)C(F)(F)F)C(=O)N1 ACQMGTBEKGXGJU-UHFFFAOYSA-N 0.000 claims description 2
- DXTMCFZBFJNDOP-UHFFFAOYSA-N 2-anilino-5-[[3-(trifluoromethyl)phenyl]methyl]-1,3-thiazol-4-one Chemical compound FC(F)(F)C1=CC=CC(CC2C(N=C(NC=3C=CC=CC=3)S2)=O)=C1 DXTMCFZBFJNDOP-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
- GWTUAJSBEZTXJX-UHFFFAOYSA-N 3-methyl-2-(4-methylphenyl)imino-5-[[3-(trifluoromethyl)phenyl]methyl]-1,3-thiazolidin-4-one Chemical compound S1C(=NC=2C=CC(C)=CC=2)N(C)C(=O)C1CC1=CC=CC(C(F)(F)F)=C1 GWTUAJSBEZTXJX-UHFFFAOYSA-N 0.000 claims description 2
- KXPAJSAIUIKHHH-UHFFFAOYSA-N 4-chloro-n-[4-oxo-5-[[3-(trifluoromethyl)phenyl]methyl]-1,3-thiazol-2-yl]benzamide Chemical compound FC(F)(F)C1=CC=CC(CC2C(NC(S2)=NC(=O)C=2C=CC(Cl)=CC=2)=O)=C1 KXPAJSAIUIKHHH-UHFFFAOYSA-N 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- WDLCSKLLZQXZRZ-UHFFFAOYSA-N phenyl n-[4-oxo-5-[[3-(trifluoromethyl)phenyl]methyl]-1,3-thiazol-2-yl]carbamate Chemical compound FC(F)(F)C1=CC=CC(CC2C(NC(S2)=NC(=O)OC=2C=CC=CC=2)=O)=C1 WDLCSKLLZQXZRZ-UHFFFAOYSA-N 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 105
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 92
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 87
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 70
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 53
- 210000004027 cell Anatomy 0.000 description 46
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 41
- 239000000203 mixture Substances 0.000 description 41
- 235000019439 ethyl acetate Nutrition 0.000 description 40
- 238000003818 flash chromatography Methods 0.000 description 38
- 239000007787 solid Substances 0.000 description 38
- NOLHRFLIXVQPSZ-UHFFFAOYSA-N 1,3-thiazolidin-4-one Chemical compound O=C1CSCN1 NOLHRFLIXVQPSZ-UHFFFAOYSA-N 0.000 description 35
- 238000006243 chemical reaction Methods 0.000 description 35
- 239000011541 reaction mixture Substances 0.000 description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 26
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- 239000012043 crude product Substances 0.000 description 21
- 238000010898 silica gel chromatography Methods 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- 239000003480 eluent Substances 0.000 description 20
- 125000001841 imino group Chemical group [H]N=* 0.000 description 20
- 239000000243 solution Substances 0.000 description 20
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 239000002585 base Substances 0.000 description 18
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- 239000012074 organic phase Substances 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000000843 powder Substances 0.000 description 15
- 241000699670 Mus sp. Species 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 125000004122 cyclic group Chemical group 0.000 description 12
- 150000002431 hydrogen Chemical class 0.000 description 12
- 125000001424 substituent group Chemical group 0.000 description 12
- GMCZUVIOJIKTIC-UHFFFAOYSA-N dithiazolidine Chemical compound C1CSSN1 GMCZUVIOJIKTIC-UHFFFAOYSA-N 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 11
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 description 10
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 10
- 229960000583 acetic acid Drugs 0.000 description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
- 239000000651 prodrug Substances 0.000 description 10
- 229940002612 prodrug Drugs 0.000 description 10
- 230000035755 proliferation Effects 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 9
- VNKRYYYOMJCILX-UHFFFAOYSA-N O=C1NCSC1CC1=CC(C(F)(F)F)=CC=C1 Chemical compound O=C1NCSC1CC1=CC(C(F)(F)F)=CC=C1 VNKRYYYOMJCILX-UHFFFAOYSA-N 0.000 description 9
- 235000011054 acetic acid Nutrition 0.000 description 9
- 239000008346 aqueous phase Substances 0.000 description 9
- 125000004429 atom Chemical group 0.000 description 9
- 239000000460 chlorine Substances 0.000 description 9
- 125000000524 functional group Chemical group 0.000 description 9
- 235000020778 linoleic acid Nutrition 0.000 description 9
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 9
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 8
- 125000005842 heteroatom Chemical group 0.000 description 8
- 239000003981 vehicle Substances 0.000 description 8
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 7
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 239000012230 colorless oil Substances 0.000 description 7
- SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 7
- 235000021588 free fatty acids Nutrition 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 239000003208 petroleum Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 206010060378 Hyperinsulinaemia Diseases 0.000 description 6
- 206010027476 Metastases Diseases 0.000 description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
- 125000001309 chloro group Chemical group Cl* 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 125000001188 haloalkyl group Chemical group 0.000 description 6
- 230000003451 hyperinsulinaemic effect Effects 0.000 description 6
- 201000008980 hyperinsulinism Diseases 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 230000009401 metastasis Effects 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- 125000004076 pyridyl group Chemical group 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- LWRUIMYWCYBHAP-UHFFFAOYSA-N 2-(4-methylanilino)-1,3-thiazol-4-one Chemical compound C1=CC(C)=CC=C1NC1=NC(=O)CS1 LWRUIMYWCYBHAP-UHFFFAOYSA-N 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 5
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- 125000003342 alkenyl group Chemical group 0.000 description 5
- 239000005557 antagonist Substances 0.000 description 5
- 230000004663 cell proliferation Effects 0.000 description 5
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 239000002953 phosphate buffered saline Substances 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 125000003107 substituted aryl group Chemical group 0.000 description 5
- GJGROPRLXDXIAN-UHFFFAOYSA-N 1,3-thiazol-4-one Chemical compound O=C1CSC=N1 GJGROPRLXDXIAN-UHFFFAOYSA-N 0.000 description 4
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
- IYGBTPGRKGQPLW-UHFFFAOYSA-N 2-anilino-1,3-thiazol-4-one Chemical compound O=C1CSC(NC=2C=CC=CC=2)=N1 IYGBTPGRKGQPLW-UHFFFAOYSA-N 0.000 description 4
- NTPLXRHDUXRPNE-UHFFFAOYSA-N 4-methoxyacetophenone Chemical compound COC1=CC=C(C(C)=O)C=C1 NTPLXRHDUXRPNE-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 230000018199 S phase Effects 0.000 description 4
- 125000002947 alkylene group Chemical group 0.000 description 4
- 125000002619 bicyclic group Chemical group 0.000 description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 230000022131 cell cycle Effects 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 210000002540 macrophage Anatomy 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 4
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 4
- XOAGWHBBYSSMOR-UHFFFAOYSA-N 2-(4-ethoxyanilino)-1,3-thiazol-4-one Chemical compound C1=CC(OCC)=CC=C1NC1=NC(=O)CS1 XOAGWHBBYSSMOR-UHFFFAOYSA-N 0.000 description 3
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| DE102005024012A1 (de) * | 2005-05-20 | 2006-11-23 | Grünenthal GmbH | Verwendung von 2,5-disubstituierten Thiazol-4-on-Derivaten in Arzneimitteln |
| WO2008065409A2 (en) * | 2006-12-01 | 2008-06-05 | Betagenon Ab | Combination for use in the treatment of cancer, comprising tamoxifen or an aromatase inhibitor |
| WO2008090327A1 (en) * | 2007-01-22 | 2008-07-31 | Betagenon Ab | New combination for use in the treatment of cancer |
| EP2136809A4 (en) * | 2007-03-20 | 2012-01-04 | Curis Inc | INHIBITORS OF RAF KINASE CONTAINING A ZINC BINDING FRAGMENT |
| CN101274918A (zh) * | 2007-03-30 | 2008-10-01 | 中国科学院上海药物研究所 | 一类取代五元杂环化合物,其制备方法和医学用途 |
| AR067769A1 (es) * | 2007-08-03 | 2009-10-21 | Betagenon Ab | Derivado de ditiazol para el tratamiento del cancer |
| JP5567481B2 (ja) | 2007-10-09 | 2014-08-06 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | グルコキナーゼアクチベーターとして有用なピリジン誘導体 |
| EP2217235A4 (en) * | 2007-11-15 | 2011-01-12 | Musc Found For Res Dev | INHIBITORS OF PIM PROTEIN KINASES, COMPOSITIONS AND METHOD FOR THE TREATMENT OF CANCER |
| KR100998572B1 (ko) * | 2007-12-14 | 2010-12-07 | 한국생명공학연구원 | 단백질 포스파타제의 활성을 억제하는 페닐아미노티아졸론유도체 또는 이의 약학적으로 허용가능한 염을유효성분으로 함유하는 암 예방 및 치료용 조성물 |
| WO2010073011A2 (en) | 2008-12-23 | 2010-07-01 | Betagenon Ab | Compounds useful as medicaments |
| WO2010086613A1 (en) | 2009-01-30 | 2010-08-05 | Betagenon Ab | Compounds useful as inhibitors as ampk |
| AU2010270030B2 (en) | 2009-07-08 | 2015-12-24 | Baltic Bio Ab | 1, 2, 4-thiazolidin-3-one derivatives and their use in the treatment of cancer |
| US9221773B2 (en) * | 2009-12-22 | 2015-12-29 | The Translational Genomics Research Institute | Benzamide derivatives |
| US8865754B2 (en) | 2011-03-03 | 2014-10-21 | Proteotech Inc. | Compounds for the treatment of neurodegenerative diseases |
| US8722670B2 (en) * | 2011-09-30 | 2014-05-13 | Bristol-Myers Squibb Company | Selective NR2B antagonists |
| WO2013108026A1 (en) | 2012-01-17 | 2013-07-25 | Baltic Bio Ab | Thiadiazolone derivatives useful in the treatment of diabetes |
| CN104059060B (zh) * | 2014-05-30 | 2017-08-01 | 西安交通大学 | 一种5‑(1h‑吲哚‑3‑亚甲基)‑1,3‑噻唑烷‑4‑酮类衍生物及其合成方法和应用 |
| WO2021028518A1 (de) * | 2019-08-15 | 2021-02-18 | Bayer Aktiengesellschaft | Verfahren zur herstellung von 2-(phenylimino)-3-alkyl-1,3-thiazolidin-4-onen |
| EP4448492B1 (en) | 2021-12-17 | 2026-03-04 | Reglagene, Inc. | Compositions and methods of making and using small molecules in the treatment of cancer |
| US12215102B2 (en) | 2023-02-28 | 2025-02-04 | Reglagene, Inc. | Compositions and methods for making and using small molecules for tubulin-targeted therapy in the treatment of cancers and related conditions |
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| US3345374A (en) * | 1962-09-04 | 1967-10-03 | Bayer Ag | Certain oxathiazole and dithiazole derivatives |
| US3671537A (en) * | 1969-06-05 | 1972-06-20 | Gyogyszerkutato Intezet | Certain 3-(2,6-dichlorophenyl)-2-iminothiazolidines |
| US4103018A (en) * | 1976-10-12 | 1978-07-25 | Schering Corporation | 2-[4-(Polyhalo-2-hydroxy-2-propyl)anilino]-2-oxazolin-4-ones and thiazolin-4-ones corresponding thereto |
| HU191408B (en) * | 1984-04-25 | 1987-02-27 | Egis Gyogyszergyar,Hu | Process for preparing new imino-thiazolidine derivatives |
| DD246541A1 (de) * | 1986-01-27 | 1987-06-10 | Univ Halle Wittenberg | Verfahren zur herstellung von 5-arylidenthiazolidin-4-onen |
| DD270072A1 (de) * | 1988-03-14 | 1989-07-19 | Univ Halle Wittenberg | Verfahren zur herstellung von 5-aryliden- hoch 2-thiazolin-4-onen |
| US6353006B1 (en) * | 1999-01-14 | 2002-03-05 | Bayer Corporation | Substituted 2-arylimino heterocycles and compositions containing them, for use as progesterone receptor binding agents |
| US20040152667A1 (en) * | 2002-10-23 | 2004-08-05 | Hauske James R. | 4-Alkenylthiazoles comprising epoxide functionality, and methods of use thereof |
| WO2005082363A1 (en) * | 2004-02-20 | 2005-09-09 | Board Of Regents, The University Of Texas System | Thiazolone compounds for treatment of cancer |
| CA2564751A1 (en) * | 2004-04-30 | 2005-11-24 | Schering Corporation | Neuropeptide receptor modulators |
| EP1765817A1 (en) * | 2004-07-01 | 2007-03-28 | F.Hoffmann-La Roche Ag | Thiazolinone unsubstituted quinolines |
| JP2008509912A (ja) * | 2004-08-10 | 2008-04-03 | エグゼリクシス， インコーポレイテッド | 医薬品としての複素環化合物 |
| RU2405782C2 (ru) * | 2004-10-14 | 2010-12-10 | Ф.Хоффманн-Ля Рош Аг | Хиназолинилметилентиазолиноны в качестве cdk-1 ингибиторов |
| CN100525929C (zh) * | 2005-04-20 | 2009-08-12 | 郭文礼 | 喷水枪出水控制装置 |
| JP2009500351A (ja) * | 2005-07-04 | 2009-01-08 | ドクター レディズ ラボラトリーズ リミテッド | Ａｍｐｋアクチベータとしてのチアゾール誘導体 |
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| WO2007010281A2 (en) | 2007-01-25 |
| CA2615752A1 (en) | 2007-01-25 |
| KR20080032096A (ko) | 2008-04-14 |
| EA200800303A1 (ru) | 2008-10-30 |
| AU2006271383A1 (en) | 2007-01-25 |
| AU2006271375A1 (en) | 2007-01-25 |
| WO2007010281A3 (en) | 2007-06-07 |
| AU2006271375A2 (en) | 2007-01-25 |
| WO2007010273A3 (en) | 2007-05-10 |
| US20090136472A1 (en) | 2009-05-28 |
| EA200800302A1 (ru) | 2008-08-29 |
| CA2614327A1 (en) | 2007-01-25 |
| WO2007010273A2 (en) | 2007-01-25 |
| EP1906955A2 (en) | 2008-04-09 |
| JP2009501776A (ja) | 2009-01-22 |
| US20090156644A1 (en) | 2009-06-18 |
| IL188163A0 (en) | 2008-03-20 |
| JP2009501775A (ja) | 2009-01-22 |
| NO20076420L (no) | 2008-04-09 |
| IL188031A0 (en) | 2011-08-01 |
| NO20076333L (no) | 2008-04-01 |
| EP1906956A2 (en) | 2008-04-09 |
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