JP2017503786A5 - - Google Patents
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- JP2017503786A5 JP2017503786A5 JP2016541128A JP2016541128A JP2017503786A5 JP 2017503786 A5 JP2017503786 A5 JP 2017503786A5 JP 2016541128 A JP2016541128 A JP 2016541128A JP 2016541128 A JP2016541128 A JP 2016541128A JP 2017503786 A5 JP2017503786 A5 JP 2017503786A5
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- benzo
- dioxide
- dihydro
- phenyl
- 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.)
- Granted
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- -1 2-oxotetrahydrofuran-3-yl Chemical group 0.000 claims description 413
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 266
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 158
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 138
- 235000019260 propionic acid Nutrition 0.000 claims description 135
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims description 123
- 150000001875 compounds Chemical class 0.000 claims description 34
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 32
- 239000001257 hydrogen Substances 0.000 claims description 27
- 229910052739 hydrogen Inorganic materials 0.000 claims description 27
- 239000000203 mixture Substances 0.000 claims description 25
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 claims description 18
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- KBUVKGMVZDAWOJ-UHFFFAOYSA-N 3h-oxathiazepine Chemical compound C=1C=COSNC=1 KBUVKGMVZDAWOJ-UHFFFAOYSA-N 0.000 claims description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 57
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims 34
- 150000003839 salts Chemical class 0.000 claims 26
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 24
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 13
- 125000001309 chloro group Chemical group Cl* 0.000 claims 6
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims 5
- 125000000217 alkyl group Chemical group 0.000 claims 5
- 206010019280 Heart failures Diseases 0.000 claims 4
- 125000001475 halogen functional group Chemical group 0.000 claims 4
- 125000002883 imidazolyl group Chemical group 0.000 claims 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 4
- 125000005936 piperidyl group Chemical group 0.000 claims 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 4
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims 3
- 208000009304 Acute Kidney Injury Diseases 0.000 claims 3
- 208000033626 Renal failure acute Diseases 0.000 claims 3
- 201000011040 acute kidney failure Diseases 0.000 claims 3
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 3
- 125000004076 pyridyl group Chemical group 0.000 claims 3
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims 2
- 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims 2
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Chemical compound C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 claims 2
- HXXOPVULXOEHTK-UHFFFAOYSA-N 4-methyl-1,3-dioxol-2-one Chemical compound CC1=COC(=O)O1 HXXOPVULXOEHTK-UHFFFAOYSA-N 0.000 claims 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims 2
- 208000024827 Alzheimer disease Diseases 0.000 claims 2
- 206010016654 Fibrosis Diseases 0.000 claims 2
- 208000024412 Friedreich ataxia Diseases 0.000 claims 2
- 208000032376 Lung infection Diseases 0.000 claims 2
- 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims 2
- 208000018737 Parkinson disease Diseases 0.000 claims 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims 2
- 230000001684 chronic effect Effects 0.000 claims 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims 2
- 208000035475 disorder Diseases 0.000 claims 2
- 125000002541 furyl group Chemical group 0.000 claims 2
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 claims 2
- KQNPFQTWMSNSAP-UHFFFAOYSA-M isobutyrate Chemical compound CC(C)C([O-])=O KQNPFQTWMSNSAP-UHFFFAOYSA-M 0.000 claims 2
- 208000019423 liver disease Diseases 0.000 claims 2
- 125000002757 morpholinyl group Chemical group 0.000 claims 2
- 201000006417 multiple sclerosis Diseases 0.000 claims 2
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims 2
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 2
- 125000001544 thienyl group Chemical group 0.000 claims 2
- YXGFOCDXNTYPPR-UHFFFAOYSA-N (1-methylpyrrolidin-3-yl) propanoate Chemical compound CCC(=O)OC1CCN(C)C1 YXGFOCDXNTYPPR-UHFFFAOYSA-N 0.000 claims 1
- RZDVYTYOVMEPBY-HSZRJFAPSA-N (3R)-3-[3-[[benzenesulfonyl(methyl)amino]methyl]-4-methylphenyl]-3-(1,4-dimethylbenzotriazol-5-yl)propanoic acid Chemical compound CN1N=NC2=C1C=CC(=C2C)[C@H](CC(=O)O)C1=CC(=C(C=C1)C)CN(S(=O)(=O)C1=CC=CC=C1)C RZDVYTYOVMEPBY-HSZRJFAPSA-N 0.000 claims 1
- RZDVYTYOVMEPBY-QHCPKHFHSA-N (3S)-3-[3-[[benzenesulfonyl(methyl)amino]methyl]-4-methylphenyl]-3-(1,4-dimethylbenzotriazol-5-yl)propanoic acid Chemical compound CN1N=NC2=C1C=CC(=C2C)[C@@H](CC(=O)O)C1=CC(=C(C=C1)C)CN(S(=O)(=O)C1=CC=CC=C1)C RZDVYTYOVMEPBY-QHCPKHFHSA-N 0.000 claims 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- ASHQFKBZKJYEQG-UHFFFAOYSA-N 2-(1-methylbenzotriazol-5-yl)propanoic acid Chemical compound OC(=O)C(C)C1=CC=C2N(C)N=NC2=C1 ASHQFKBZKJYEQG-UHFFFAOYSA-N 0.000 claims 1
- UVSPBAFXKQMDBG-UHFFFAOYSA-N 2-(dimethylamino)ethyl propanoate Chemical compound CCC(=O)OCCN(C)C UVSPBAFXKQMDBG-UHFFFAOYSA-N 0.000 claims 1
- SFAMKDPMPDEXGH-UHFFFAOYSA-N 2-hydroxyethyl propanoate Chemical compound CCC(=O)OCCO SFAMKDPMPDEXGH-UHFFFAOYSA-N 0.000 claims 1
- SFUSXTAJJNOGFY-UHFFFAOYSA-N 3-(1,4-dimethylbenzotriazol-5-yl)-3-[3-[[2-hydroxyethyl-(2-methoxypyridin-3-yl)sulfonylamino]methyl]-4-methylphenyl]propanoic acid Chemical compound CN1N=NC2=C1C=CC(=C2C)C(CC(=O)O)C1=CC(=C(C=C1)C)CN(S(=O)(=O)C=1C(=NC=CC=1)OC)CCO SFUSXTAJJNOGFY-UHFFFAOYSA-N 0.000 claims 1
- VYACXBSULJEWPY-UHFFFAOYSA-N 3-(1,4-dimethylbenzotriazol-5-yl)-3-[4-methyl-3-[(5-methyl-3,4-dihydro-1,2,5-benzothiadiazepin-2-yl)methyl]phenyl]propan-1-ol Chemical compound CN1N=NC2=C1C=CC(=C2C)C(CCO)C=1C=CC(=C(CN2SC3=C(N(CC2)C)C=CC=C3)C=1)C VYACXBSULJEWPY-UHFFFAOYSA-N 0.000 claims 1
- XZLRJCSXDLXBSC-UHFFFAOYSA-N 3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl 2-cyanoacetate Chemical group CC(C)(C)OC(=O)NCCCOC(=O)CC#N XZLRJCSXDLXBSC-UHFFFAOYSA-N 0.000 claims 1
- CCKFFZWASQCQFD-UHFFFAOYSA-N 3-[3-[[(3-acetamidophenyl)sulfonyl-methylamino]methyl]-4-chlorophenyl]-3-(1-methylbenzotriazol-5-yl)propanoic acid Chemical compound C(C)(=O)NC=1C=C(C=CC=1)S(=O)(=O)N(C)CC=1C=C(C=CC=1Cl)C(CC(=O)O)C1=CC2=C(N(N=N2)C)C=C1 CCKFFZWASQCQFD-UHFFFAOYSA-N 0.000 claims 1
- AEWQYTMJBRTVCM-UHFFFAOYSA-N 3-[3-[[2-hydroxyethyl-(2-methoxypyridin-3-yl)sulfonylamino]methyl]-4-methylphenyl]-3-(7-methoxy-1-methylbenzotriazol-5-yl)propanoic acid Chemical compound OCCN(S(=O)(=O)C=1C(=NC=CC=1)OC)CC=1C=C(C=CC=1C)C(CC(=O)O)C1=CC2=C(N(N=N2)C)C(=C1)OC AEWQYTMJBRTVCM-UHFFFAOYSA-N 0.000 claims 1
- QJFXAWTUFRGEDO-UHFFFAOYSA-N 3-[3-[[benzenesulfonyl(methyl)amino]methyl]-4-methylphenyl]-3-(1-methylbenzotriazol-5-yl)propanoic acid Chemical compound CN1N=NC2=C1C=CC(=C2)C(CC(=O)O)C1=CC(=C(C=C1)C)CN(S(=O)(=O)C1=CC=CC=C1)C QJFXAWTUFRGEDO-UHFFFAOYSA-N 0.000 claims 1
- TYEFYUBZAKPDAX-UHFFFAOYSA-N 3-[3-[[cyclopentylsulfonyl(methyl)amino]methyl]-4-methylphenyl]-3-(1,4-dimethylbenzotriazol-5-yl)propanoic acid Chemical compound CN1N=NC2=C1C=CC(=C2C)C(CC(=O)O)C1=CC(=C(C=C1)C)CN(S(=O)(=O)C1CCCC1)C TYEFYUBZAKPDAX-UHFFFAOYSA-N 0.000 claims 1
- SRPXGGSRYJJWSO-UHFFFAOYSA-N 3-[4-chloro-3-[[(1,5-dimethylpyrazol-4-yl)sulfonyl-methylamino]methyl]phenyl]-3-(1-methylbenzotriazol-5-yl)propanoic acid Chemical compound ClC1=C(C=C(C=C1)C(CC(=O)O)C1=CC2=C(N(N=N2)C)C=C1)CN(S(=O)(=O)C=1C=NN(C=1C)C)C SRPXGGSRYJJWSO-UHFFFAOYSA-N 0.000 claims 1
- CPQNNJBTSHDTLZ-UHFFFAOYSA-N 3-[4-chloro-3-[[2,3-dihydro-1,4-benzodioxin-6-ylsulfonyl(methyl)amino]methyl]phenyl]-3-(1-methylbenzotriazol-5-yl)propanoic acid Chemical compound ClC1=C(C=C(C=C1)C(CC(=O)O)C1=CC2=C(N(N=N2)C)C=C1)CN(S(=O)(=O)C1=CC2=C(OCCO2)C=C1)C CPQNNJBTSHDTLZ-UHFFFAOYSA-N 0.000 claims 1
- MLPSEERETBAFEP-UHFFFAOYSA-N 3-[4-chloro-3-[[2,3-dihydro-1H-inden-5-ylsulfonyl(methyl)amino]methyl]phenyl]-3-(1-methylbenzotriazol-5-yl)propanoic acid Chemical compound ClC1=C(C=C(C=C1)C(CC(=O)O)C1=CC2=C(N(N=N2)C)C=C1)CN(S(=O)(=O)C=1C=C2CCCC2=CC=1)C MLPSEERETBAFEP-UHFFFAOYSA-N 0.000 claims 1
- XDOGAMNAMXXKOO-UHFFFAOYSA-N 3-[4-chloro-3-[[ethyl(pyridin-3-ylsulfonyl)amino]methyl]phenyl]-3-(1-methylbenzotriazol-5-yl)propanoic acid Chemical compound ClC1=C(C=C(C=C1)C(CC(=O)O)C1=CC2=C(N(N=N2)C)C=C1)CN(S(=O)(=O)C=1C=NC=CC=1)CC XDOGAMNAMXXKOO-UHFFFAOYSA-N 0.000 claims 1
- USDLDJOPUXHGLC-UHFFFAOYSA-N 3-[4-chloro-3-[[methyl(methylsulfonyl)amino]methyl]phenyl]-3-(1-methylbenzotriazol-5-yl)propanoic acid Chemical compound ClC1=C(C=C(C=C1)C(CC(=O)O)C1=CC2=C(N(N=N2)C)C=C1)CN(S(=O)(=O)C)C USDLDJOPUXHGLC-UHFFFAOYSA-N 0.000 claims 1
- LALJNFCDDXCGMH-UHFFFAOYSA-N 3-[4-chloro-3-[[methyl-(3-methylphenyl)sulfonylamino]methyl]phenyl]-3-(1-methylbenzotriazol-5-yl)propanoic acid Chemical compound ClC1=C(C=C(C=C1)C(CC(=O)O)C1=CC2=C(N(N=N2)C)C=C1)CN(S(=O)(=O)C1=CC(=CC=C1)C)C LALJNFCDDXCGMH-UHFFFAOYSA-N 0.000 claims 1
- FKGLABWENBSNRH-UHFFFAOYSA-N 3-[4-chloro-3-[[methyl-(4-methylphenyl)sulfonylamino]methyl]phenyl]-3-(1-methylbenzotriazol-5-yl)propanoic acid Chemical compound ClC1=C(C=C(C=C1)C(CC(=O)O)C1=CC2=C(N(N=N2)C)C=C1)CN(S(=O)(=O)C1=CC=C(C=C1)C)C FKGLABWENBSNRH-UHFFFAOYSA-N 0.000 claims 1
- FRBDZDVSXHHBHW-UHFFFAOYSA-N 3-[4-chloro-3-[[propyl(pyridin-3-ylsulfonyl)amino]methyl]phenyl]-3-(1-methylbenzotriazol-5-yl)propanoic acid Chemical compound ClC1=C(C=C(C=C1)C(CC(=O)O)C1=CC2=C(N(N=N2)C)C=C1)CN(S(=O)(=O)C=1C=NC=CC=1)CCC FRBDZDVSXHHBHW-UHFFFAOYSA-N 0.000 claims 1
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 1
- 201000001320 Atherosclerosis Diseases 0.000 claims 1
- 206010003805 Autism Diseases 0.000 claims 1
- 208000020706 Autistic disease Diseases 0.000 claims 1
- 208000023275 Autoimmune disease Diseases 0.000 claims 1
- HBOBNYBQNVWMAG-UHFFFAOYSA-N CCC(C1=CC(=C(C=C1)C)CN(C)S(=O)(=O)C2=CC=CC=C2)C3=CC4=C(C(=C3)OC)N(N=N4)C Chemical compound CCC(C1=CC(=C(C=C1)C)CN(C)S(=O)(=O)C2=CC=CC=C2)C3=CC4=C(C(=C3)OC)N(N=N4)C HBOBNYBQNVWMAG-UHFFFAOYSA-N 0.000 claims 1
- SEKQCRHQWAMDJD-UHFFFAOYSA-N CCC(C1=CC(=C(C=C1)Cl)CN(C)S(=O)(=O)C2CCCCC2)C3=CC4=C(C=C3)N(N=N4)C Chemical compound CCC(C1=CC(=C(C=C1)Cl)CN(C)S(=O)(=O)C2CCCCC2)C3=CC4=C(C=C3)N(N=N4)C SEKQCRHQWAMDJD-UHFFFAOYSA-N 0.000 claims 1
- QELVGHPHZFVKIU-NRFANRHFSA-N CC[C@@H](C1=CC(=C(C=C1)Cl)CN(C)S(=O)(=O)C2=CC=CC=C2)C3=CC4=C(C=C3)N(N=N4)C Chemical compound CC[C@@H](C1=CC(=C(C=C1)Cl)CN(C)S(=O)(=O)C2=CC=CC=C2)C3=CC4=C(C=C3)N(N=N4)C QELVGHPHZFVKIU-NRFANRHFSA-N 0.000 claims 1
- QELVGHPHZFVKIU-OAQYLSRUSA-N CC[C@H](C1=CC(=C(C=C1)Cl)CN(C)S(=O)(=O)C2=CC=CC=C2)C3=CC4=C(C=C3)N(N=N4)C Chemical compound CC[C@H](C1=CC(=C(C=C1)Cl)CN(C)S(=O)(=O)C2=CC=CC=C2)C3=CC4=C(C=C3)N(N=N4)C QELVGHPHZFVKIU-OAQYLSRUSA-N 0.000 claims 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 claims 1
- 201000003883 Cystic fibrosis Diseases 0.000 claims 1
- 201000004624 Dermatitis Diseases 0.000 claims 1
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims 1
- 206010072082 Environmental exposure Diseases 0.000 claims 1
- 206010073306 Exposure to radiation Diseases 0.000 claims 1
- 206010019799 Hepatitis viral Diseases 0.000 claims 1
- 206010020772 Hypertension Diseases 0.000 claims 1
- 206010062016 Immunosuppression Diseases 0.000 claims 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims 1
- 208000019693 Lung disease Diseases 0.000 claims 1
- 201000004681 Psoriasis Diseases 0.000 claims 1
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 claims 1
- 206010040047 Sepsis Diseases 0.000 claims 1
- 206010046851 Uveitis Diseases 0.000 claims 1
- 208000024716 acute asthma Diseases 0.000 claims 1
- 230000001154 acute effect Effects 0.000 claims 1
- 102000015395 alpha 1-Antitrypsin Human genes 0.000 claims 1
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 claims 1
- 229940024142 alpha 1-antitrypsin Drugs 0.000 claims 1
- 208000008445 altitude sickness Diseases 0.000 claims 1
- 208000006673 asthma Diseases 0.000 claims 1
- 125000005605 benzo group Chemical group 0.000 claims 1
- GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 claims 1
- 208000023819 chronic asthma Diseases 0.000 claims 1
- 208000020832 chronic kidney disease Diseases 0.000 claims 1
- 230000007882 cirrhosis Effects 0.000 claims 1
- 208000019425 cirrhosis of liver Diseases 0.000 claims 1
- 208000029742 colonic neoplasm Diseases 0.000 claims 1
- 230000007850 degeneration Effects 0.000 claims 1
- 208000033679 diabetic kidney disease Diseases 0.000 claims 1
- 125000004639 dihydroindenyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000004064 dysfunction Effects 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- 230000003511 endothelial effect Effects 0.000 claims 1
- 230000004761 fibrosis Effects 0.000 claims 1
- 230000001506 immunosuppresive effect Effects 0.000 claims 1
- 230000002757 inflammatory effect Effects 0.000 claims 1
- 208000014674 injury Diseases 0.000 claims 1
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 claims 1
- 210000003734 kidney Anatomy 0.000 claims 1
- 208000017169 kidney disease Diseases 0.000 claims 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
- 229960005489 paracetamol Drugs 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 claims 1
- 201000011461 pre-eclampsia Diseases 0.000 claims 1
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims 1
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims 1
- 125000003226 pyrazolyl group Chemical group 0.000 claims 1
- DZABSSLCAIHBIK-UHFFFAOYSA-N pyrrolidin-3-ylmethyl propanoate Chemical compound CCC(=O)OCC1CCNC1 DZABSSLCAIHBIK-UHFFFAOYSA-N 0.000 claims 1
- 230000005855 radiation Effects 0.000 claims 1
- 125000003831 tetrazolyl group Chemical group 0.000 claims 1
- 239000003053 toxin Substances 0.000 claims 1
- 231100000765 toxin Toxicity 0.000 claims 1
- 108700012359 toxins Proteins 0.000 claims 1
- 238000002054 transplantation Methods 0.000 claims 1
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- 201000001862 viral hepatitis Diseases 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 38
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 34
- 239000011541 reaction mixture Substances 0.000 description 29
- 239000000243 solution Substances 0.000 description 25
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 21
- 235000019439 ethyl acetate Nutrition 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 230000014759 maintenance of location Effects 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 13
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 238000004007 reversed phase HPLC Methods 0.000 description 8
- 239000012267 brine Substances 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 241000534944 Thia Species 0.000 description 5
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
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| EP3576726A1 (en) | 2017-02-06 | 2019-12-11 | Massachusetts Institute Of Technology | Methods and products related to glutaminase inhibitors |
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2014
- 2014-12-17 KR KR1020167018852A patent/KR102301867B1/ko active Active
- 2014-12-17 MX MX2016008134A patent/MX370410B/es active IP Right Grant
- 2014-12-17 CN CN201480069879.3A patent/CN105829305B/zh active Active
- 2014-12-17 EA EA201691259A patent/EA030431B1/ru not_active IP Right Cessation
- 2014-12-17 WO PCT/IB2014/067027 patent/WO2015092713A1/en not_active Ceased
- 2014-12-17 EP EP14827868.2A patent/EP3083614B1/en active Active
- 2014-12-17 US US15/105,306 patent/US10144731B2/en active Active
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2016
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