KR20110050615A - 항종양 활성을 가지는 ｈｓｐ90 조절성 5-페닐-이속사졸-3-카르복사미드 - Google Patents
항종양 활성을 가지는 ｈｓｐ90 조절성 5-페닐-이속사졸-3-카르복사미드 Download PDFInfo
- Publication number
- KR20110050615A KR20110050615A KR1020117000312A KR20117000312A KR20110050615A KR 20110050615 A KR20110050615 A KR 20110050615A KR 1020117000312 A KR1020117000312 A KR 1020117000312A KR 20117000312 A KR20117000312 A KR 20117000312A KR 20110050615 A KR20110050615 A KR 20110050615A
- Authority
- KR
- South Korea
- Prior art keywords
- isoxazole
- phenyl
- dihydroxy
- carboxylic acid
- chloro
- 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.)
- Ceased
Links
- 102100034051 Heat shock protein HSP 90-alpha Human genes 0.000 title claims abstract description 26
- 101710113864 Heat shock protein 90 Proteins 0.000 title abstract description 6
- 230000000259 anti-tumor effect Effects 0.000 title abstract description 4
- 230000001105 regulatory effect Effects 0.000 title description 2
- ASVXNFGUPSDDTA-UHFFFAOYSA-N 5-phenyl-1,2-oxazole-3-carboxamide Chemical compound O1N=C(C(=O)N)C=C1C1=CC=CC=C1 ASVXNFGUPSDDTA-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 73
- 101001016865 Homo sapiens Heat shock protein HSP 90-alpha Proteins 0.000 claims abstract description 23
- 239000003814 drug Substances 0.000 claims abstract description 22
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 17
- 201000011510 cancer Diseases 0.000 claims abstract description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
- -1 3- (4-Methylpiperazin-1-yl) propaneamido Chemical group 0.000 claims description 68
- 125000000217 alkyl group Chemical group 0.000 claims description 52
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 39
- 239000000203 mixture Substances 0.000 claims description 36
- 238000000034 method Methods 0.000 claims description 32
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 23
- 125000003118 aryl group Chemical group 0.000 claims description 20
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- 125000003342 alkenyl group Chemical group 0.000 claims description 15
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 150000002367 halogens Chemical group 0.000 claims description 15
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 14
- 125000001072 heteroaryl group Chemical group 0.000 claims description 13
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
- 125000001188 haloalkyl group Chemical group 0.000 claims description 12
- 230000000694 effects Effects 0.000 claims description 10
- JLLYLQLDYORLBB-UHFFFAOYSA-N 5-bromo-n-methylthiophene-2-sulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(Br)S1 JLLYLQLDYORLBB-UHFFFAOYSA-N 0.000 claims description 8
- 125000003282 alkyl amino group Chemical group 0.000 claims description 8
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 8
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 8
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 8
- 235000019988 mead Nutrition 0.000 claims description 8
- 238000003786 synthesis reaction Methods 0.000 claims description 8
- 201000006474 Brain Ischemia Diseases 0.000 claims description 7
- 206010008120 Cerebral ischaemia Diseases 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
- 230000015572 biosynthetic process Effects 0.000 claims description 7
- 206010008118 cerebral infarction Diseases 0.000 claims description 7
- 208000027866 inflammatory disease Diseases 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 230000004770 neurodegeneration Effects 0.000 claims description 7
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 6
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 6
- FPGYLUIGKHTKQV-UHFFFAOYSA-N chembl1940917 Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(Cl)C=2)O)=C1NC(=O)C=1SC=CC=1C FPGYLUIGKHTKQV-UHFFFAOYSA-N 0.000 claims description 6
- NRDHRUUAIBGJLZ-UHFFFAOYSA-N chembl1940919 Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(Cl)C=2)O)=C1NC(=O)C(C)(C)C NRDHRUUAIBGJLZ-UHFFFAOYSA-N 0.000 claims description 6
- ZAHKLNMQDKMBCL-UHFFFAOYSA-N chembl1940921 Chemical compound C1C(C2)CC(C3)CC2CC13C(=O)NC=1C(C(=O)NCC)=NOC=1C1=CC(Cl)=C(O)C=C1O ZAHKLNMQDKMBCL-UHFFFAOYSA-N 0.000 claims description 6
- CLGCYNQGBOFRIU-UHFFFAOYSA-N chembl1940924 Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(Cl)C=2)O)=C1NC(=O)CCN1CCOCC1 CLGCYNQGBOFRIU-UHFFFAOYSA-N 0.000 claims description 6
- KBNLPGKGXMPKID-UHFFFAOYSA-N chembl1940925 Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(C(C)C)C=2)O)=C1NC(C)=O KBNLPGKGXMPKID-UHFFFAOYSA-N 0.000 claims description 6
- NBPOVHXUKYASOM-UHFFFAOYSA-N chembl1940926 Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(C(C)C)C=2)O)=C1NC(=O)C(C)(C)C NBPOVHXUKYASOM-UHFFFAOYSA-N 0.000 claims description 6
- UOWFKIGORLIVGO-UHFFFAOYSA-N chembl1941063 Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(C(C)C)C=2)O)=C1NC(=O)C=1SC=CC=1C UOWFKIGORLIVGO-UHFFFAOYSA-N 0.000 claims description 6
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- PYLUIBKRCIOZQM-UHFFFAOYSA-N 5-(2,4-dihydroxy-5-propan-2-ylphenyl)-N-ethyl-4-[methyl-(4-morpholin-4-ylbenzoyl)amino]-1,2-oxazole-3-carboxamide hydrochloride Chemical compound Cl.C(C)NC(=O)C1=NOC(=C1N(C(C1=CC=C(C=C1)N1CCOCC1)=O)C)C1=C(C=C(C(=C1)C(C)C)O)O PYLUIBKRCIOZQM-UHFFFAOYSA-N 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 5
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 5
- UWKWOTCLGZNOKY-UHFFFAOYSA-N chembl1940913 Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(Cl)C=2)O)=C1NC(=O)C1=CC=C(Br)C=C1 UWKWOTCLGZNOKY-UHFFFAOYSA-N 0.000 claims description 5
- QBSZQEVMVGSPFZ-UHFFFAOYSA-N chembl1940914 Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(Cl)C=2)O)=C1NC(=O)C1=CC=C(OC)C=C1 QBSZQEVMVGSPFZ-UHFFFAOYSA-N 0.000 claims description 5
- MQYOAYAUVZORFG-UHFFFAOYSA-N chembl1940915 Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(Cl)C=2)O)=C1NC(=O)C1=CC=C(OC)C(OC)=C1 MQYOAYAUVZORFG-UHFFFAOYSA-N 0.000 claims description 5
- WASBTDRFRYYYRL-UHFFFAOYSA-N chembl1940916 Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(Cl)C=2)O)=C1NC(=O)C1=CC(OC)=C(OC)C(OC)=C1 WASBTDRFRYYYRL-UHFFFAOYSA-N 0.000 claims description 5
- WEAJPAPZLYQPRZ-UHFFFAOYSA-N chembl1940918 Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(Cl)C=2)O)=C1NC(C)=O WEAJPAPZLYQPRZ-UHFFFAOYSA-N 0.000 claims description 5
- VIEGTSLOUDDFCN-UHFFFAOYSA-N chembl1940920 Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(Cl)C=2)O)=C1NC(=O)C=C VIEGTSLOUDDFCN-UHFFFAOYSA-N 0.000 claims description 5
- WURSGCMBSCSYOG-UHFFFAOYSA-N chembl1941050 Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(C(C)C)C=2)O)=C1NC(=O)CCN1CCOCC1 WURSGCMBSCSYOG-UHFFFAOYSA-N 0.000 claims description 5
- BYAGRVGRUDLLDR-UHFFFAOYSA-N chembl1941052 Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(C(C)C)C=2)O)=C1NC(=O)C1=CC=C(OC)C=C1 BYAGRVGRUDLLDR-UHFFFAOYSA-N 0.000 claims description 5
- RKZLDDWBCRFJFY-UHFFFAOYSA-N chembl1941073 Chemical compound C=1C=C2C=CNC2=CC=1C(=O)NC=1C(C(=O)NCC)=NOC=1C1=CC(C(C)C)=C(O)C=C1O RKZLDDWBCRFJFY-UHFFFAOYSA-N 0.000 claims description 5
- SURLAOAQRDUOFO-UHFFFAOYSA-N chembl1941081 Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(Cl)C=2)O)=C1NCC1=CC=C(OC)C=C1 SURLAOAQRDUOFO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 5
- 230000001225 therapeutic effect Effects 0.000 claims description 5
- MUZNLZVOKJVBPC-UHFFFAOYSA-N 5-(2,4-dihydroxy-5-propan-2-ylphenyl)-N-ethyl-4-[(4-methoxycyclohexanecarbonyl)amino]-1,2-oxazole-3-carboxamide Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(C(C)C)C=2)O)=C1NC(=O)C1CCC(OC)CC1 MUZNLZVOKJVBPC-UHFFFAOYSA-N 0.000 claims description 4
- CCPBQNNFEFGOGY-UHFFFAOYSA-N 5-[5-(2,4-dihydroxy-5-propan-2-ylphenyl)-3-(ethylcarbamoyl)-1,2-oxazol-4-yl]-3-N-ethyl-2H-1,2-oxazole-3,5-dicarboxamide Chemical compound C(C)NC(=O)C1=NOC(=C1C1(C=C(NO1)C(=O)NCC)C(=O)N)C1=C(C=C(C(=C1)C(C)C)O)O CCPBQNNFEFGOGY-UHFFFAOYSA-N 0.000 claims description 4
- 206010063094 Cerebral malaria Diseases 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 4
- QCKQEYDGLASTLI-UHFFFAOYSA-N chembl1940923 Chemical compound C1=CC(OC)=CC=C1C(=O)NC1=C(C=2C(=CC(O)=C(Cl)C=2)O)ON=C1C(=O)N1CC(F)(F)C1 QCKQEYDGLASTLI-UHFFFAOYSA-N 0.000 claims description 4
- OOHHYUCVSBGXHT-UHFFFAOYSA-N chembl1941082 Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(Cl)C=2)O)=C1NC1CCCCC1 OOHHYUCVSBGXHT-UHFFFAOYSA-N 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- UXYRXGFUANQKTA-UHFFFAOYSA-N 1,2-oxazole-3-carboxylic acid Chemical compound OC(=O)C=1C=CON=1 UXYRXGFUANQKTA-UHFFFAOYSA-N 0.000 claims description 3
- TZYANCKBMDGFOB-UHFFFAOYSA-N 4-[(4-aminocyclohexanecarbonyl)amino]-5-(2,4-dihydroxy-5-propan-2-ylphenyl)-N-ethyl-1,2-oxazole-3-carboxamide Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(C(C)C)C=2)O)=C1NC(=O)C1CCC(N)CC1 TZYANCKBMDGFOB-UHFFFAOYSA-N 0.000 claims description 3
- HAMKBSLGCXVDLO-UHFFFAOYSA-N 4-[[4-(aminomethyl)cyclohexanecarbonyl]amino]-5-(2,4-dihydroxy-5-propan-2-ylphenyl)-N-ethyl-1,2-oxazole-3-carboxamide Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(C(C)C)C=2)O)=C1NC(=O)C1CCC(CN)CC1 HAMKBSLGCXVDLO-UHFFFAOYSA-N 0.000 claims description 3
- 208000023275 Autoimmune disease Diseases 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- IYYXMUJIVUJPBD-UHFFFAOYSA-N N-[5-(5-chloro-2,4-dihydroxyphenyl)-3-(4-methylpiperazine-1-carbonyl)-1,2-oxazol-4-yl]-4-methoxybenzamide Chemical compound C1=CC(OC)=CC=C1C(=O)NC1=C(C=2C(=CC(O)=C(Cl)C=2)O)ON=C1C(=O)N1CCN(C)CC1 IYYXMUJIVUJPBD-UHFFFAOYSA-N 0.000 claims description 3
- FPBCOFYFVBCSPA-UHFFFAOYSA-N chembl1941083 Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(Cl)C=2)O)=C1NC1CCN(C)CC1 FPBCOFYFVBCSPA-UHFFFAOYSA-N 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 230000036541 health Effects 0.000 claims description 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 3
- 150000002576 ketones Chemical class 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 230000001575 pathological effect Effects 0.000 claims description 3
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 2
- 208000024827 Alzheimer disease Diseases 0.000 claims description 2
- 206010003591 Ataxia Diseases 0.000 claims description 2
- UGWIQBFFHSHNDU-UHFFFAOYSA-N CC(C)C1=C(C=C(C(=C1)C2=C(C(=NO2)C(=O)O)NC(=O)C3CCC(CC3)C(C)(C)C)O)O Chemical compound CC(C)C1=C(C=C(C(=C1)C2=C(C(=NO2)C(=O)O)NC(=O)C3CCC(CC3)C(C)(C)C)O)O UGWIQBFFHSHNDU-UHFFFAOYSA-N 0.000 claims description 2
- VJPGZONQVSCVJS-UHFFFAOYSA-N CCNC(=O)C1=NOC=C1C1=CC(C(C)C)=C(O)C=C1O Chemical compound CCNC(=O)C1=NOC=C1C1=CC(C(C)C)=C(O)C=C1O VJPGZONQVSCVJS-UHFFFAOYSA-N 0.000 claims description 2
- 208000023105 Huntington disease Diseases 0.000 claims description 2
- 206010020565 Hyperaemia Diseases 0.000 claims description 2
- 208000009829 Lewy Body Disease Diseases 0.000 claims description 2
- 201000002832 Lewy body dementia Diseases 0.000 claims description 2
- 208000018737 Parkinson disease Diseases 0.000 claims description 2
- 150000001263 acyl chlorides Chemical class 0.000 claims description 2
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 2
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 239000003638 chemical reducing agent Substances 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 claims description 2
- 230000003071 parasitic effect Effects 0.000 claims description 2
- 239000002798 polar solvent Substances 0.000 claims description 2
- 210000000278 spinal cord Anatomy 0.000 claims description 2
- QXPZOKVSFMRGMQ-UHFFFAOYSA-N trifluoromethylcyclohexane Chemical compound FC(F)(F)C1CCCCC1 QXPZOKVSFMRGMQ-UHFFFAOYSA-N 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims 4
- PYIUZSMHFSNQNA-UHFFFAOYSA-N 4-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-1,2-oxazole-3-carboxamide Chemical compound CCNC(=O)C1=NOC=C1C1=CC(Cl)=C(O)C=C1O PYIUZSMHFSNQNA-UHFFFAOYSA-N 0.000 claims 1
- 206010005003 Bladder cancer Diseases 0.000 claims 1
- 208000003174 Brain Neoplasms Diseases 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 208000012902 Nervous system disease Diseases 0.000 claims 1
- 208000025966 Neurological disease Diseases 0.000 claims 1
- 206010033128 Ovarian cancer Diseases 0.000 claims 1
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 1
- 239000003153 chemical reaction reagent Substances 0.000 claims 1
- 208000024519 eye neoplasm Diseases 0.000 claims 1
- 208000014829 head and neck neoplasm Diseases 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- 208000026037 malignant tumor of neck Diseases 0.000 claims 1
- 208000037819 metastatic cancer Diseases 0.000 claims 1
- 208000011575 metastatic malignant neoplasm Diseases 0.000 claims 1
- 201000008106 ocular cancer Diseases 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
- 201000002628 peritoneum cancer Diseases 0.000 claims 1
- 201000003437 pleural cancer Diseases 0.000 claims 1
- 201000005112 urinary bladder cancer Diseases 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 abstract description 8
- 201000010099 disease Diseases 0.000 abstract description 7
- 108010006519 Molecular Chaperones Proteins 0.000 abstract description 4
- 102000005431 Molecular Chaperones Human genes 0.000 abstract description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 37
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 13
- 239000007787 solid Substances 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000003481 heat shock protein 90 inhibitor Substances 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- BWFGXQOWFKYXOZ-UHFFFAOYSA-N 5-[5-chloro-2,4-bis(phenylmethoxy)phenyl]-n-ethyl-4-nitro-1,2-oxazole-3-carboxamide Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(OCC=3C=CC=CC=3)=C(Cl)C=2)OCC=2C=CC=CC=2)=C1[N+]([O-])=O BWFGXQOWFKYXOZ-UHFFFAOYSA-N 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 238000003818 flash chromatography Methods 0.000 description 5
- 238000002875 fluorescence polarization Methods 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- IOOMXAQUNPWDLL-UHFFFAOYSA-N 2-[6-(diethylamino)-3-(diethyliminiumyl)-3h-xanthen-9-yl]-5-sulfobenzene-1-sulfonate Chemical compound C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=C(S(O)(=O)=O)C=C1S([O-])(=O)=O IOOMXAQUNPWDLL-UHFFFAOYSA-N 0.000 description 4
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- QACSKDRRGBHPOF-UHFFFAOYSA-N ethyl 5-[5-chloro-2,4-bis(phenylmethoxy)phenyl]-1,2-oxazole-3-carboxylate Chemical compound O1N=C(C(=O)OCC)C=C1C(C(=C1)OCC=2C=CC=CC=2)=CC(Cl)=C1OCC1=CC=CC=C1 QACSKDRRGBHPOF-UHFFFAOYSA-N 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- QTQAWLPCGQOSGP-GBTDJJJQSA-N geldanamycin Chemical compound N1C(=O)\C(C)=C/C=C\[C@@H](OC)[C@H](OC(N)=O)\C(C)=C/[C@@H](C)[C@@H](O)[C@H](OC)C[C@@H](C)CC2=C(OC)C(=O)C=C1C2=O QTQAWLPCGQOSGP-GBTDJJJQSA-N 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- CVJQCEUAIVQCDK-UHFFFAOYSA-N 1-(5-chloro-2,4-dihydroxyphenyl)ethanone Chemical compound CC(=O)C1=CC(Cl)=C(O)C=C1O CVJQCEUAIVQCDK-UHFFFAOYSA-N 0.000 description 3
- KEUCDMZJTGJAQX-UHFFFAOYSA-N 1-[5-chloro-2,4-bis(phenylmethoxy)phenyl]ethanone Chemical compound C1=C(OCC=2C=CC=CC=2)C(C(=O)C)=CC(Cl)=C1OCC1=CC=CC=C1 KEUCDMZJTGJAQX-UHFFFAOYSA-N 0.000 description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical class CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
- JKTQYVXIHSTRDD-UHFFFAOYSA-N 4-amino-5-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-1,2-oxazole-3-carboxamide Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(Cl)C=2)O)=C1N JKTQYVXIHSTRDD-UHFFFAOYSA-N 0.000 description 3
- WAKROMYHSIMZFY-UHFFFAOYSA-N 4-amino-5-[5-chloro-2,4-bis(phenylmethoxy)phenyl]-n-ethyl-1,2-oxazole-3-carboxamide Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(OCC=3C=CC=CC=3)=C(Cl)C=2)OCC=2C=CC=CC=2)=C1N WAKROMYHSIMZFY-UHFFFAOYSA-N 0.000 description 3
- MYEXHIZUUXNARE-UHFFFAOYSA-N 5-[5-chloro-2,4-bis(phenylmethoxy)phenyl]-n-ethyl-1,2-oxazole-3-carboxamide Chemical compound O1N=C(C(=O)NCC)C=C1C(C(=C1)OCC=2C=CC=CC=2)=CC(Cl)=C1OCC1=CC=CC=C1 MYEXHIZUUXNARE-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- JRZJKWGQFNTSRN-UHFFFAOYSA-N Geldanamycin Natural products C1C(C)CC(OC)C(O)C(C)C=C(C)C(OC(N)=O)C(OC)CCC=C(C)C(=O)NC2=CC(=O)C(OC)=C1C2=O JRZJKWGQFNTSRN-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 230000001028 anti-proliverative effect Effects 0.000 description 3
- 239000000010 aprotic solvent Substances 0.000 description 3
- FREXQSXQFGJSPD-UHFFFAOYSA-N chembl1940927 Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(C(C)C)C=2)O)=C1NC(=O)C1CCCCC1 FREXQSXQFGJSPD-UHFFFAOYSA-N 0.000 description 3
- NNPUKYHSBUTURK-IYARVYRRSA-N chembl1940928 Chemical compound C1C[C@@H](CCCCC)CC[C@@H]1C(=O)NC1=C(C=2C(=CC(O)=C(C(C)C)C=2)O)ON=C1C(=O)NCC NNPUKYHSBUTURK-IYARVYRRSA-N 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 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 3
- 235000019439 ethyl acetate Nutrition 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000011550 stock solution Substances 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 2
- INVJBYOXKDTRAB-UHFFFAOYSA-N 3,3-difluoroazetidine-1-carbaldehyde Chemical compound FC1(F)CN(C=O)C1 INVJBYOXKDTRAB-UHFFFAOYSA-N 0.000 description 2
- WHUNSZBDQCBJQO-UHFFFAOYSA-N 4-acetamido-5-[5-chloro-2,4-bis(phenylmethoxy)phenyl]-n-ethyl-1,2-oxazole-3-carboxamide Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(OCC=3C=CC=CC=3)=C(Cl)C=2)OCC=2C=CC=CC=2)=C1NC(C)=O WHUNSZBDQCBJQO-UHFFFAOYSA-N 0.000 description 2
- ADQACDHOUOIMAK-UHFFFAOYSA-N 4-amino-5-[2,4-bis(phenylmethoxy)-5-propan-2-ylphenyl]-n-ethyl-1,2-oxazole-3-carboxamide Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(OCC=3C=CC=CC=3)=C(C(C)C)C=2)OCC=2C=CC=CC=2)=C1N ADQACDHOUOIMAK-UHFFFAOYSA-N 0.000 description 2
- SJDOHMRKSZXBMK-UHFFFAOYSA-N 5-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-nitro-1,2-oxazole-3-carboxamide Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(Cl)C=2)O)=C1[N+]([O-])=O SJDOHMRKSZXBMK-UHFFFAOYSA-N 0.000 description 2
- IRUQDZYRLKBZPY-UHFFFAOYSA-N 5-[5-chloro-2,4-bis(phenylmethoxy)phenyl]-1,2-oxazole-3-carboxylic acid Chemical compound O1N=C(C(=O)O)C=C1C(C(=C1)OCC=2C=CC=CC=2)=CC(Cl)=C1OCC1=CC=CC=C1 IRUQDZYRLKBZPY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 241000700198 Cavia Species 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- 241000282887 Suidae Species 0.000 description 2
- DKGJFBKYLFXAAJ-GSGGJQAMSA-N [(4E,8S,9S,10E,12S,13R,14S,16Z)-13,20,22-trihydroxy-8,14,19-trimethoxy-4,10,12,16-tetramethyl-3-oxo-2-azabicyclo[16.3.1]docosa-1(21),4,6,10,16,18(22),19-heptaen-9-yl] carbamate Chemical compound CO[C@H]1C\C(C)=C/c2c(O)c(NC(=O)\C(C)=C\C=C[C@H](OC)[C@@H](OC(N)=O)\C(C)=C\[C@H](C)[C@H]1O)cc(O)c2OC DKGJFBKYLFXAAJ-GSGGJQAMSA-N 0.000 description 2
- 238000010640 amide synthesis reaction Methods 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 230000003833 cell viability Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- ZSKNESXDGZRCNG-UHFFFAOYSA-N chembl1940929 Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(C(C)C)C=2)O)=C1NC(=O)C1CCC(C(F)(F)F)CC1 ZSKNESXDGZRCNG-UHFFFAOYSA-N 0.000 description 2
- ZHOPMAPGOGTAOR-UHFFFAOYSA-N chembl1940931 Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(C(C)C)C=2)O)=C1NC(=O)C1CCC(C(C)(C)C)CC1 ZHOPMAPGOGTAOR-UHFFFAOYSA-N 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 239000000890 drug combination Substances 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 239000012456 homogeneous solution Substances 0.000 description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 150000002545 isoxazoles Chemical class 0.000 description 2
- 125000000842 isoxazolyl group Chemical group 0.000 description 2
- 201000004792 malaria Diseases 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- LHNUEBNTPQPHKG-UHFFFAOYSA-N methyl 5-[[[5-(5-chloro-2,4-dihydroxyphenyl)-3-(ethylcarbamoyl)-1,2-oxazol-4-yl]amino]methyl]-1,2-oxazole-3-carboxylate Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(Cl)C=2)O)=C1NCC1=CC(C(=O)OC)=NO1 LHNUEBNTPQPHKG-UHFFFAOYSA-N 0.000 description 2
- VYGYNVZNSSTDLJ-HKCOAVLJSA-N monorden Natural products CC1CC2OC2C=C/C=C/C(=O)CC3C(C(=CC(=C3Cl)O)O)C(=O)O1 VYGYNVZNSSTDLJ-HKCOAVLJSA-N 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- AECPBJMOGBFQDN-YMYQVXQQSA-N radicicol Chemical compound C1CCCC(=O)C[C@H]2[C@H](Cl)C(=O)CC(=O)[C@H]2C(=O)O[C@H](C)C[C@H]2O[C@@H]21 AECPBJMOGBFQDN-YMYQVXQQSA-N 0.000 description 2
- 229930192524 radicicol Natural products 0.000 description 2
- 239000000700 radioactive tracer Substances 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- AYUNIORJHRXIBJ-TXHRRWQRSA-N tanespimycin Chemical compound N1C(=O)\C(C)=C\C=C/[C@H](OC)[C@@H](OC(N)=O)\C(C)=C\[C@H](C)[C@@H](O)[C@@H](OC)C[C@H](C)CC2=C(NCC=C)C(=O)C=C1C2=O AYUNIORJHRXIBJ-TXHRRWQRSA-N 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- FTJHKZQHQDKPFJ-UHFFFAOYSA-N (carbamoylamino)carbamic acid Chemical compound NC(=O)NNC(O)=O FTJHKZQHQDKPFJ-UHFFFAOYSA-N 0.000 description 1
- KIPSRYDSZQRPEA-UHFFFAOYSA-N 2,2,2-trifluoroethanamine Chemical compound NCC(F)(F)F KIPSRYDSZQRPEA-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- QUHVRXKSQHIZNV-UHFFFAOYSA-N 3,3-difluoroazetidine Chemical compound FC1(F)CNC1 QUHVRXKSQHIZNV-UHFFFAOYSA-N 0.000 description 1
- XPQPCDFVNITMSY-UHFFFAOYSA-N 3-[5-chloro-2,4-bis(phenylmethoxy)phenyl]-1,2-oxazole-5-carboxylic acid Chemical compound O1C(C(=O)O)=CC(C=2C(=CC(OCC=3C=CC=CC=3)=C(Cl)C=2)OCC=2C=CC=CC=2)=N1 XPQPCDFVNITMSY-UHFFFAOYSA-N 0.000 description 1
- WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 description 1
- XNNRAUOEJJPCTG-UHFFFAOYSA-N 3-ethyl-2H-1,2-oxazole-3,5-dicarboxamide Chemical compound C(C)C1(NOC(=C1)C(=O)N)C(=O)N XNNRAUOEJJPCTG-UHFFFAOYSA-N 0.000 description 1
- CXSJCULPCNWMCT-UHFFFAOYSA-N 4-(adamantane-1-carbonylamino)-5-(2,4-dihydroxy-5-propan-2-ylphenyl)-N-ethyl-1,2-oxazole-3-carboxamide Chemical compound C1C(C2)CC(C3)CC2CC13C(=O)NC=1C(C(=O)NCC)=NOC=1C1=CC(C(C)C)=C(O)C=C1O CXSJCULPCNWMCT-UHFFFAOYSA-N 0.000 description 1
- ZIMVGVPKIKECLW-UHFFFAOYSA-N 4-(adamantane-1-carbonylamino)-5-[5-chloro-2,4-bis(phenylmethoxy)phenyl]-n-ethyl-1,2-oxazole-3-carboxamide Chemical compound C1C(C2)CC(C3)CC2CC13C(=O)NC=1C(C(=O)NCC)=NOC=1C(C(=C1)OCC=2C=CC=CC=2)=CC(Cl)=C1OCC1=CC=CC=C1 ZIMVGVPKIKECLW-UHFFFAOYSA-N 0.000 description 1
- YCEITAYVODNFFB-UHFFFAOYSA-N 4-[(4-bromobenzoyl)amino]-5-(2,4-dihydroxy-5-propan-2-ylphenyl)-N-ethyl-1,2-oxazole-3-carboxamide Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(C(C)C)C=2)O)=C1NC(=O)C1=CC=C(Br)C=C1 YCEITAYVODNFFB-UHFFFAOYSA-N 0.000 description 1
- LGAIEBFEXMBFIL-UHFFFAOYSA-N 4-[(4-bromobenzoyl)amino]-5-[5-chloro-2,4-bis(phenylmethoxy)phenyl]-n-ethyl-1,2-oxazole-3-carboxamide Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(OCC=3C=CC=CC=3)=C(Cl)C=2)OCC=2C=CC=CC=2)=C1NC(=O)C1=CC=C(Br)C=C1 LGAIEBFEXMBFIL-UHFFFAOYSA-N 0.000 description 1
- CADKYMFSDFMGIJ-UHFFFAOYSA-N 4-acetamido-5-[2,4-bis(phenylmethoxy)-5-propan-2-ylphenyl]-n-ethyl-1,2-oxazole-3-carboxamide Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(OCC=3C=CC=CC=3)=C(C(C)C)C=2)OCC=2C=CC=CC=2)=C1NC(C)=O CADKYMFSDFMGIJ-UHFFFAOYSA-N 0.000 description 1
- JFZARAAVWNISTG-UHFFFAOYSA-N 4-amino-5-(2,4-dihydroxy-5-propan-2-ylphenyl)-N-ethyl-1,2-oxazole-3-carboxamide Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(C(C)C)C=2)O)=C1N JFZARAAVWNISTG-UHFFFAOYSA-N 0.000 description 1
- JQVAPEJNIZULEK-UHFFFAOYSA-N 4-chlorobenzene-1,3-diol Chemical compound OC1=CC=C(Cl)C(O)=C1 JQVAPEJNIZULEK-UHFFFAOYSA-N 0.000 description 1
- VCJCQTZWCRSVKF-UHFFFAOYSA-N 5-(2,4-dihydroxy-5-propan-2-ylphenyl)-4-[(3,4-dimethoxybenzoyl)amino]-N-ethyl-1,2-oxazole-3-carboxamide Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(C(C)C)C=2)O)=C1NC(=O)C1=CC=C(OC)C(OC)=C1 VCJCQTZWCRSVKF-UHFFFAOYSA-N 0.000 description 1
- ANIDUTPIZUBSKJ-UHFFFAOYSA-N 5-(2,4-dihydroxy-5-propan-2-ylphenyl)-N-ethyl-4-(prop-2-enoylamino)-1,2-oxazole-3-carboxamide Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(C(C)C)C=2)O)=C1NC(=O)C=C ANIDUTPIZUBSKJ-UHFFFAOYSA-N 0.000 description 1
- VMSGVWMEXHKVJW-UHFFFAOYSA-N 5-(2,4-dihydroxy-5-propan-2-ylphenyl)-N-ethyl-4-[(3,4,5-trimethoxybenzoyl)amino]-1,2-oxazole-3-carboxamide Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(C(C)C)C=2)O)=C1NC(=O)C1=CC(OC)=C(OC)C(OC)=C1 VMSGVWMEXHKVJW-UHFFFAOYSA-N 0.000 description 1
- DILNMOLOZGRZPP-UHFFFAOYSA-N 5-(2,4-dihydroxy-5-propan-2-ylphenyl)-N-ethyl-4-[(4-methoxyphenyl)sulfonylamino]-1,2-oxazole-3-carboxamide Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(C(C)C)C=2)O)=C1NS(=O)(=O)C1=CC=C(OC)C=C1 DILNMOLOZGRZPP-UHFFFAOYSA-N 0.000 description 1
- QAVOEBGLMLVWAK-UHFFFAOYSA-N 5-[2,4-bis(phenylmethoxy)-5-propan-2-ylphenyl]-4-(2,2-dimethylpropanoylamino)-n-ethyl-1,2-oxazole-3-carboxamide Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(OCC=3C=CC=CC=3)=C(C(C)C)C=2)OCC=2C=CC=CC=2)=C1NC(=O)C(C)(C)C QAVOEBGLMLVWAK-UHFFFAOYSA-N 0.000 description 1
- BRMJTMKDPSHGOW-UHFFFAOYSA-N 5-[2,4-bis(phenylmethoxy)-5-propan-2-ylphenyl]-n-ethyl-4-(3-morpholin-4-ylpropanoylamino)-1,2-oxazole-3-carboxamide Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(OCC=3C=CC=CC=3)=C(C(C)C)C=2)OCC=2C=CC=CC=2)=C1NC(=O)CCN1CCOCC1 BRMJTMKDPSHGOW-UHFFFAOYSA-N 0.000 description 1
- DYANRNDNWGHQQV-UHFFFAOYSA-N 5-[2,4-bis(phenylmethoxy)-5-propan-2-ylphenyl]-n-ethyl-4-[(4-methoxybenzoyl)amino]-1,2-oxazole-3-carboxamide Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(OCC=3C=CC=CC=3)=C(C(C)C)C=2)OCC=2C=CC=CC=2)=C1NC(=O)C1=CC=C(OC)C=C1 DYANRNDNWGHQQV-UHFFFAOYSA-N 0.000 description 1
- QIPAQNDIMGAAMJ-UHFFFAOYSA-N 5-[2,4-bis(phenylmethoxy)-5-propan-2-ylphenyl]-n-ethyl-4-nitro-1,2-oxazole-3-carboxamide Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(OCC=3C=CC=CC=3)=C(C(C)C)C=2)OCC=2C=CC=CC=2)=C1[N+]([O-])=O QIPAQNDIMGAAMJ-UHFFFAOYSA-N 0.000 description 1
- ILIVQNJCOJCRPH-UHFFFAOYSA-N 5-[5-chloro-2,4-bis(phenylmethoxy)phenyl]-4-(2,2-dimethylpropanoylamino)-n-ethyl-1,2-oxazole-3-carboxamide Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(OCC=3C=CC=CC=3)=C(Cl)C=2)OCC=2C=CC=CC=2)=C1NC(=O)C(C)(C)C ILIVQNJCOJCRPH-UHFFFAOYSA-N 0.000 description 1
- DLJUZIDKULMLDN-UHFFFAOYSA-N 5-[5-chloro-2,4-bis(phenylmethoxy)phenyl]-4-[(3,4-dimethoxybenzoyl)amino]-n-ethyl-1,2-oxazole-3-carboxamide Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(OCC=3C=CC=CC=3)=C(Cl)C=2)OCC=2C=CC=CC=2)=C1NC(=O)C1=CC=C(OC)C(OC)=C1 DLJUZIDKULMLDN-UHFFFAOYSA-N 0.000 description 1
- DLKZJNXWOSXNBE-UHFFFAOYSA-N 5-[5-chloro-2,4-bis(phenylmethoxy)phenyl]-4-nitro-n-(2,2,2-trifluoroethyl)-1,2-oxazole-3-carboxamide Chemical compound FC(F)(F)CNC(=O)C1=NOC(C=2C(=CC(OCC=3C=CC=CC=3)=C(Cl)C=2)OCC=2C=CC=CC=2)=C1[N+](=O)[O-] DLKZJNXWOSXNBE-UHFFFAOYSA-N 0.000 description 1
- IXDWJXUTMOGDMZ-UHFFFAOYSA-N 5-[5-chloro-2,4-bis(phenylmethoxy)phenyl]-n-ethyl-4-(3-morpholin-4-ylpropanoylamino)-1,2-oxazole-3-carboxamide Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(OCC=3C=CC=CC=3)=C(Cl)C=2)OCC=2C=CC=CC=2)=C1NC(=O)CCN1CCOCC1 IXDWJXUTMOGDMZ-UHFFFAOYSA-N 0.000 description 1
- DCTZTCHQDXIRFO-UHFFFAOYSA-N 5-[5-chloro-2,4-bis(phenylmethoxy)phenyl]-n-ethyl-4-(prop-2-enoylamino)-1,2-oxazole-3-carboxamide Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(OCC=3C=CC=CC=3)=C(Cl)C=2)OCC=2C=CC=CC=2)=C1NC(=O)C=C DCTZTCHQDXIRFO-UHFFFAOYSA-N 0.000 description 1
- JQVYTFRFFPWMAX-UHFFFAOYSA-N 5-[5-chloro-2,4-bis(phenylmethoxy)phenyl]-n-ethyl-4-[(3,4,5-trimethoxybenzoyl)amino]-1,2-oxazole-3-carboxamide Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(OCC=3C=CC=CC=3)=C(Cl)C=2)OCC=2C=CC=CC=2)=C1NC(=O)C1=CC(OC)=C(OC)C(OC)=C1 JQVYTFRFFPWMAX-UHFFFAOYSA-N 0.000 description 1
- FPXATDOLXURLQS-UHFFFAOYSA-N 5-[5-chloro-2,4-bis(phenylmethoxy)phenyl]-n-ethyl-4-[(3-methylthiophene-2-carbonyl)amino]-1,2-oxazole-3-carboxamide Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(OCC=3C=CC=CC=3)=C(Cl)C=2)OCC=2C=CC=CC=2)=C1NC(=O)C=1SC=CC=1C FPXATDOLXURLQS-UHFFFAOYSA-N 0.000 description 1
- CWNYOLYQPXNKBP-UHFFFAOYSA-N 5-[5-chloro-2,4-bis(phenylmethoxy)phenyl]-n-ethyl-4-[(4-methoxybenzoyl)amino]-1,2-oxazole-3-carboxamide Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(OCC=3C=CC=CC=3)=C(Cl)C=2)OCC=2C=CC=CC=2)=C1NC(=O)C1=CC=C(OC)C=C1 CWNYOLYQPXNKBP-UHFFFAOYSA-N 0.000 description 1
- 108091006112 ATPases Proteins 0.000 description 1
- 102000057290 Adenosine Triphosphatases Human genes 0.000 description 1
- 229910015900 BF3 Inorganic materials 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- UOCGHKPNBDOLDX-UHFFFAOYSA-N C1=C(OCC=2C=CC=CC=2)C(C(=O)C=C(O)C(=O)OCC)=CC(Cl)=C1OCC1=CC=CC=C1 Chemical compound C1=C(OCC=2C=CC=CC=2)C(C(=O)C=C(O)C(=O)OCC)=CC(Cl)=C1OCC1=CC=CC=C1 UOCGHKPNBDOLDX-UHFFFAOYSA-N 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- AFFSZNHAULCEKY-WBYSVDBMSA-N Geldanamycin Analog Chemical compound N1C(=O)\C(C)=C/C=C/C(OC)C(OC(N)=O)\C(C)=C\C(C)C(O)C(OC)CC(C)CC2=C(O)C1=CC(=O)C2=O AFFSZNHAULCEKY-WBYSVDBMSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 1
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 1
- 206010019851 Hepatotoxicity Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- BXDZOYLPNAIDOC-UHFFFAOYSA-N N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]-1-[2-[2-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]ethylamino]-2-oxoethyl]piperidine-4-carboxamide Chemical compound CC(C)(C)c1cnc(CSc2cnc(NC(=O)C3CCN(CC(=O)NCCOCCOCCOCCNc4cccc5C(=O)N(C6CCC(=O)NC6=O)C(=O)c45)CC3)s2)o1 BXDZOYLPNAIDOC-UHFFFAOYSA-N 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 1
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- 102100033479 RAF proto-oncogene serine/threonine-protein kinase Human genes 0.000 description 1
- 101710141955 RAF proto-oncogene serine/threonine-protein kinase Proteins 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 206010064390 Tumour invasion Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- WAMXMXARPDJWQU-UHFFFAOYSA-N [4-amino-5-[5-chloro-2,4-bis(phenylmethoxy)phenyl]-1,2-oxazol-3-yl]-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=NOC(C=2C(=CC(OCC=3C=CC=CC=3)=C(Cl)C=2)OCC=2C=CC=CC=2)=C1N WAMXMXARPDJWQU-UHFFFAOYSA-N 0.000 description 1
- ZCJVOILPGQRKJT-UHFFFAOYSA-N [5-[5-chloro-2,4-bis(phenylmethoxy)phenyl]-1,2-oxazol-3-yl]-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=NOC(C=2C(=CC(OCC=3C=CC=CC=3)=C(Cl)C=2)OCC=2C=CC=CC=2)=C1 ZCJVOILPGQRKJT-UHFFFAOYSA-N 0.000 description 1
- QZONGGRECUYAST-UHFFFAOYSA-N [5-[5-chloro-2,4-bis(phenylmethoxy)phenyl]-4-nitro-1,2-oxazol-3-yl]-(3,3-difluoroazetidin-1-yl)methanone Chemical compound [O-][N+](=O)C=1C(C(=O)N2CC(F)(F)C2)=NOC=1C(C(=C1)OCC=2C=CC=CC=2)=CC(Cl)=C1OCC1=CC=CC=C1 QZONGGRECUYAST-UHFFFAOYSA-N 0.000 description 1
- HISNKJRPJWKDBS-UHFFFAOYSA-N [5-[5-chloro-2,4-bis(phenylmethoxy)phenyl]-4-nitro-1,2-oxazol-3-yl]-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=NOC(C=2C(=CC(OCC=3C=CC=CC=3)=C(Cl)C=2)OCC=2C=CC=CC=2)=C1[N+]([O-])=O HISNKJRPJWKDBS-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- MXMOTZIXVICDSD-UHFFFAOYSA-N anisoyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C=C1 MXMOTZIXVICDSD-UHFFFAOYSA-N 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 125000001769 aryl amino group Chemical group 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
- 150000008316 benzisoxazoles Chemical class 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 230000009702 cancer cell proliferation Effects 0.000 description 1
- 230000009400 cancer invasion Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000006727 cell loss Effects 0.000 description 1
- HRPBHBHGGWTKSC-UHFFFAOYSA-N chembl1940922 Chemical compound C1=CC(OC)=CC=C1C(=O)NC1=C(C=2C(=CC(O)=C(Cl)C=2)O)ON=C1C(=O)NCC(F)(F)F HRPBHBHGGWTKSC-UHFFFAOYSA-N 0.000 description 1
- KOTBAIQNUOXZTF-UBRLZZGHSA-N chembl1940932 Chemical compound Cl.CCNC(=O)C1=NOC(C=2C(=CC(O)=C(C(C)C)C=2)O)=C1NC(=O)[C@H]1CC[C@H](N)CC1 KOTBAIQNUOXZTF-UBRLZZGHSA-N 0.000 description 1
- ZUMXEIICVTUABZ-SKKCDYJJSA-N chembl1940933 Chemical compound Cl.CCNC(=O)C1=NOC(C=2C(=CC(O)=C(C(C)C)C=2)O)=C1NC(=O)[C@H]1CC[C@H](CN)CC1 ZUMXEIICVTUABZ-SKKCDYJJSA-N 0.000 description 1
- IAVMWVMXDJRTHT-UHFFFAOYSA-N chembl1941051 Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(C(C)C)C=2)O)=C1NC(=O)CCN1CCN(C)CC1 IAVMWVMXDJRTHT-UHFFFAOYSA-N 0.000 description 1
- UDIGLEOGQYIBNW-UHFFFAOYSA-N chembl1941080 Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(O)=C(Cl)C=2)O)=C1NCC=1SC=CC=1C UDIGLEOGQYIBNW-UHFFFAOYSA-N 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 125000006310 cycloalkyl amino group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000002784 cytotoxicity assay Methods 0.000 description 1
- 231100000263 cytotoxicity test Toxicity 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 1
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 238000007598 dipping method Methods 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000010981 drying operation Methods 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- QPMJENKZJUFOON-PLNGDYQASA-N ethyl (z)-3-chloro-2-cyano-4,4,4-trifluorobut-2-enoate Chemical compound CCOC(=O)C(\C#N)=C(/Cl)C(F)(F)F QPMJENKZJUFOON-PLNGDYQASA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 108010074605 gamma-Globulins Proteins 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 230000007686 hepatotoxicity Effects 0.000 description 1
- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 238000013537 high throughput screening Methods 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- ZTUJDPKOHPKRMO-UHFFFAOYSA-N hydron;2,2,2-trifluoroethanamine;chloride Chemical compound Cl.NCC(F)(F)F ZTUJDPKOHPKRMO-UHFFFAOYSA-N 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 125000005990 isobenzothienyl group Chemical group 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- UKMJQQCCSXZEFG-UHFFFAOYSA-N methyl 5-[[5-[2,4-bis(phenylmethoxy)-5-propan-2-ylphenyl]-3-(ethylcarbamoyl)-1,2-oxazol-4-yl]carbamoyl]-1,2-oxazole-3-carboxylate Chemical compound CCNC(=O)C1=NOC(C=2C(=CC(OCC=3C=CC=CC=3)=C(C(C)C)C=2)OCC=2C=CC=CC=2)=C1NC(=O)C1=CC(C(=O)OC)=NO1 UKMJQQCCSXZEFG-UHFFFAOYSA-N 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
- VYKALIRICXHOJI-UHFFFAOYSA-N n-[5-[5-chloro-2,4-bis(phenylmethoxy)phenyl]-3-(3,3-difluoroazetidine-1-carbonyl)-1,2-oxazol-4-yl]-4-methoxybenzamide Chemical compound C1=CC(OC)=CC=C1C(=O)NC1=C(C=2C(=CC(OCC=3C=CC=CC=3)=C(Cl)C=2)OCC=2C=CC=CC=2)ON=C1C(=O)N1CC(F)(F)C1 VYKALIRICXHOJI-UHFFFAOYSA-N 0.000 description 1
- OXXNMVLKDRBTFM-UHFFFAOYSA-N n-[5-[5-chloro-2,4-bis(phenylmethoxy)phenyl]-3-(4-methylpiperazine-1-carbonyl)-1,2-oxazol-4-yl]-4-methoxybenzamide Chemical compound C1=CC(OC)=CC=C1C(=O)NC1=C(C=2C(=CC(OCC=3C=CC=CC=3)=C(Cl)C=2)OCC=2C=CC=CC=2)ON=C1C(=O)N1CCN(C)CC1 OXXNMVLKDRBTFM-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- JZWQGHAERZIZGM-UHFFFAOYSA-N n-ethyl-1,2-oxazole-3-carboxamide Chemical compound CCNC(=O)C=1C=CON=1 JZWQGHAERZIZGM-UHFFFAOYSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000017095 negative regulation of cell growth Effects 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- IWELDVXSEVIIGI-UHFFFAOYSA-N piperazin-2-one Chemical compound O=C1CNCCN1 IWELDVXSEVIIGI-UHFFFAOYSA-N 0.000 description 1
- BXRNXXXXHLBUKK-UHFFFAOYSA-N piperazine-2,5-dione Chemical compound O=C1CNC(=O)CN1 BXRNXXXXHLBUKK-UHFFFAOYSA-N 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinyl group Chemical group C1(O)=CC(O)=CC=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 108020003113 steroid hormone receptors Proteins 0.000 description 1
- 102000005969 steroid hormone receptors Human genes 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229950007866 tanespimycin Drugs 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- DDWBRNXDKNIQDY-UHFFFAOYSA-N thieno[2,3-d]pyrimidine Chemical compound N1=CN=C2SC=CC2=C1 DDWBRNXDKNIQDY-UHFFFAOYSA-N 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 231100000588 tumorigenic Toxicity 0.000 description 1
- 230000000381 tumorigenic effect Effects 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D261/18—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/06—Antimalarials
-
- 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
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D261/14—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Neurosurgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Psychology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Anesthesiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Transplantation (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Oncology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP08159692.6 | 2008-07-04 | ||
| EP08159692 | 2008-07-04 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20110050615A true KR20110050615A (ko) | 2011-05-16 |
Family
ID=40019071
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020117000312A Ceased KR20110050615A (ko) | 2008-07-04 | 2009-06-30 | 항종양 활성을 가지는 ｈｓｐ90 조절성 5-페닐-이속사졸-3-카르복사미드 |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US8383616B2 (enExample) |
| EP (1) | EP2310377B1 (enExample) |
| JP (1) | JP5640002B2 (enExample) |
| KR (1) | KR20110050615A (enExample) |
| CN (1) | CN102083804A (enExample) |
| AR (1) | AR072793A1 (enExample) |
| AU (1) | AU2009265745B2 (enExample) |
| BR (1) | BRPI0913834A2 (enExample) |
| CA (1) | CA2729710A1 (enExample) |
| EA (1) | EA019793B1 (enExample) |
| IL (1) | IL210200A0 (enExample) |
| MX (1) | MX2010013913A (enExample) |
| MY (1) | MY150604A (enExample) |
| NZ (1) | NZ590861A (enExample) |
| SG (1) | SG192464A1 (enExample) |
| TW (1) | TWI450898B (enExample) |
| WO (1) | WO2010000748A1 (enExample) |
| ZA (1) | ZA201100007B (enExample) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8236838B2 (en) * | 2008-04-21 | 2012-08-07 | Institute For Oneworld Health | Compounds, compositions and methods comprising isoxazole derivatives |
| US8343976B2 (en) | 2009-04-20 | 2013-01-01 | Institute For Oneworld Health | Compounds, compositions and methods comprising pyrazole derivatives |
| WO2012058271A2 (en) | 2010-10-27 | 2012-05-03 | Pixelligent Technologies, Llc | Synthesis, capping and dispersion of nanocrystals |
| KR101275264B1 (ko) * | 2011-08-24 | 2013-06-17 | 포항공과대학교 산학협력단 | 샤프로닌 단백질의 조절 물질 탐색 방법 |
| CN103724269B (zh) * | 2012-10-11 | 2016-12-21 | 中国科学院上海药物研究所 | 苯基1,2-异噁唑或苯基1,2-吡唑类化合物及其用途 |
| MA39483A (fr) * | 2014-03-18 | 2015-09-24 | Synta Pharmaceuticals Corp | Agents thérapeutiques cibles |
| WO2016054560A1 (en) * | 2014-10-02 | 2016-04-07 | Flatley Discovery Lab | Isoxazole compounds and methods for the treatment of cystic fibrosis |
| US10870651B2 (en) | 2014-12-23 | 2020-12-22 | Dana-Farber Cancer Institute, Inc. | Inhibitors of cyclin-dependent kinase 7 (CDK7) |
| CN104725329B (zh) * | 2015-01-13 | 2017-01-18 | 陕西科技大学 | 一种具有抗肿瘤活性的异恶唑羧酸类化合物及其合成方法 |
| CN107427521B (zh) | 2015-03-27 | 2021-08-03 | 达纳-法伯癌症研究所股份有限公司 | 细胞周期蛋白依赖性激酶的抑制剂 |
| CN104803934B (zh) * | 2015-05-04 | 2018-01-02 | 陕西科技大学 | 一种具有抗肿瘤活性的苯基异噁唑羧酸类化合物及其合成方法与应用 |
| IT201700081419A1 (it) | 2017-07-18 | 2019-01-18 | Rare Partners Srl | Derivati isossazolici come induttori di emoglobina fetale in precursori eritroidi derivati da pazienti beta-talassemici |
| EP3810132A4 (en) * | 2018-06-25 | 2022-06-22 | Dana-Farber Cancer Institute, Inc. | TAIRE FAMILY KINASE INHIBITORS AND RELATED USES |
| CN113164477A (zh) | 2018-12-14 | 2021-07-23 | 达纳-法伯癌症研究所股份有限公司 | C-jun-n-末端激酶的吡唑并吡啶抑制剂及其用途 |
| EP3902542A4 (en) | 2018-12-28 | 2022-09-07 | Dana-Farber Cancer Institute, Inc. | CYCLIN DEPENDENT KINASE 7 INHIBITORS AND USES THEREOF |
| CN117105880B (zh) * | 2022-10-17 | 2025-08-26 | 上海康斯维克生物医药有限公司 | 用作诱发抗原特异性反应的脲类化合物、其荧光标记物及制备方法和用途 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE420878T1 (de) * | 2000-02-18 | 2009-01-15 | Kyowa Hakko Kirin Co Ltd | Isoxazol- und thiazolverbindungen und ihre verwendung als medikamente |
| KR101166749B1 (ko) * | 2003-02-11 | 2012-07-27 | 베르날리스(캠브리지)리미티드 | 열쇼크 단백질 저해제로서의 이소옥사졸 화합물 |
| KR101394245B1 (ko) * | 2005-12-30 | 2014-05-14 | 에스케이바이오팜 주식회사 | 아이속사졸 유도체 및 이의 용도 |
| GB0603880D0 (en) * | 2006-02-27 | 2006-04-05 | Novartis Ag | Organic compounds |
| ES2384906T3 (es) * | 2007-03-01 | 2012-07-13 | Novartis Ag | Mesilato de etilamida del ácido 5-(2,4-dihidroxi-5-isopropil-fenil)-4-(4-morfolin-4-il-metil-fenil)-isoxazol-3-carboxílico, hidratos y polimorfos del mismo y formulaciones que comprenden estas formas |
-
2009
- 2009-06-17 TW TW098120258A patent/TWI450898B/zh not_active IP Right Cessation
- 2009-06-30 JP JP2011515438A patent/JP5640002B2/ja not_active Expired - Fee Related
- 2009-06-30 CA CA2729710A patent/CA2729710A1/en not_active Abandoned
- 2009-06-30 MY MYPI20105887 patent/MY150604A/en unknown
- 2009-06-30 EP EP09772448.8A patent/EP2310377B1/en not_active Not-in-force
- 2009-06-30 EA EA201170139A patent/EA019793B1/ru not_active IP Right Cessation
- 2009-06-30 KR KR1020117000312A patent/KR20110050615A/ko not_active Ceased
- 2009-06-30 MX MX2010013913A patent/MX2010013913A/es active IP Right Grant
- 2009-06-30 NZ NZ590861A patent/NZ590861A/xx not_active IP Right Cessation
- 2009-06-30 US US13/001,652 patent/US8383616B2/en not_active Expired - Fee Related
- 2009-06-30 BR BRPI0913834A patent/BRPI0913834A2/pt not_active IP Right Cessation
- 2009-06-30 CN CN2009801255931A patent/CN102083804A/zh active Pending
- 2009-06-30 WO PCT/EP2009/058205 patent/WO2010000748A1/en not_active Ceased
- 2009-06-30 AU AU2009265745A patent/AU2009265745B2/en not_active Ceased
- 2009-06-30 SG SG2013051305A patent/SG192464A1/en unknown
- 2009-07-03 AR ARP090102496A patent/AR072793A1/es unknown
-
2010
- 2010-12-23 IL IL210200A patent/IL210200A0/en unknown
-
2011
- 2011-01-03 ZA ZA2011/00007A patent/ZA201100007B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| SG192464A1 (en) | 2013-08-30 |
| EP2310377B1 (en) | 2015-09-16 |
| MX2010013913A (es) | 2011-03-03 |
| ZA201100007B (en) | 2011-10-26 |
| IL210200A0 (en) | 2011-03-31 |
| WO2010000748A1 (en) | 2010-01-07 |
| CN102083804A (zh) | 2011-06-01 |
| JP2011526594A (ja) | 2011-10-13 |
| NZ590861A (en) | 2012-08-31 |
| EP2310377A1 (en) | 2011-04-20 |
| US20110245221A1 (en) | 2011-10-06 |
| MY150604A (en) | 2014-01-30 |
| JP5640002B2 (ja) | 2014-12-10 |
| AR072793A1 (es) | 2010-09-22 |
| EA019793B1 (ru) | 2014-06-30 |
| US8383616B2 (en) | 2013-02-26 |
| TWI450898B (zh) | 2014-09-01 |
| CA2729710A1 (en) | 2010-01-07 |
| EA201170139A1 (ru) | 2011-08-30 |
| AU2009265745A1 (en) | 2010-01-07 |
| AU2009265745B2 (en) | 2013-07-04 |
| BRPI0913834A2 (pt) | 2015-10-20 |
| TW201012815A (en) | 2010-04-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2310377B1 (en) | 5-phenyl-isoxazole-3-carboxamides modulating hsp90 with antitumoral activities | |
| PL203771B1 (pl) | Pochodna bifenylosulfonamidu jako dualny antagonista receptorów angiotensyny i endoteliny, sposób jej wytwarzania i jej zastosowanie oraz pochodna bifenylu i pochodna benzenu | |
| HUT66319A (en) | Benzanilide derivatives and pharmaceutical compositions containing them | |
| CN102811998B (zh) | 新的亲环素抑制剂及其用途 | |
| SG190432A1 (en) | Neprilysin inhibitors | |
| PL205321B1 (pl) | Zastosowanie podstawionych heterocyklicznych moczników do wytwarzania leku do hamowania kinazy raf, podstawione heterocykliczne moczniki oraz kompozycja farmaceutyczna je zawierająca | |
| JP2021522253A (ja) | 化合物及びその使用 | |
| JP7408819B2 (ja) | イソインドリン誘導体、並びにその医薬組成物及び使用 | |
| JP2000500134A (ja) | ベンゾキサジン抗菌剤 | |
| US9302998B2 (en) | Aryl triazole compounds with antitumoural activity | |
| JP2007522142A (ja) | Ｉｋｋ３に対して活性を有するベンゾイミダゾール置換チオフェン誘導体 | |
| JP2009534365A (ja) | Ａｄｇ受容体修飾物質として有用なスルホンアミド化合物 | |
| NO332109B1 (no) | Nye azetidinforbindelser, fremgangsmate for fremstilling derav og mellomprodukter, anvendelse derav, samt farmasoytiske formuleringer med slike forbindelser | |
| KR19990045727A (ko) | 선택적 β３ 아드레날린 효능제 | |
| AU2021239631B2 (en) | Oxadiazole derivative | |
| EP0446010B1 (en) | Imidazole derivatives and antiepileptics comprising said imidazole derivatives as effective ingredients | |
| HK1158191A (en) | 5-phenyl-isoxazole-3-carboxamides modulating hsp90 with antitumoral activities | |
| CN118047779B (zh) | 含苯联杂芳基的二氢喋啶酮衍生物及其用途 | |
| KR20120109667A (ko) | 열쇼크 단백질의 활성을 저해하는 신규 화합물 | |
| HK40086571B (en) | Oxadiazole derivative |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20110106 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| A201 | Request for examination | ||
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 20130703 Comment text: Request for Examination of Application |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20140926 Patent event code: PE09021S01D |
|
| E601 | Decision to refuse application | ||
| PE0601 | Decision on rejection of patent |
Patent event date: 20150626 Comment text: Decision to Refuse Application Patent event code: PE06012S01D Patent event date: 20140926 Comment text: Notification of reason for refusal Patent event code: PE06011S01I |