AU2010309920A1 - Diazepam derivatives as modulators of chemokine receptors - Google Patents
Diazepam derivatives as modulators of chemokine receptors Download PDFInfo
- Publication number
- AU2010309920A1 AU2010309920A1 AU2010309920A AU2010309920A AU2010309920A1 AU 2010309920 A1 AU2010309920 A1 AU 2010309920A1 AU 2010309920 A AU2010309920 A AU 2010309920A AU 2010309920 A AU2010309920 A AU 2010309920A AU 2010309920 A1 AU2010309920 A1 AU 2010309920A1
- Authority
- AU
- Australia
- Prior art keywords
- alkyl
- oxo
- hydroxy
- spiro
- methyl
- 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.)
- Abandoned
Links
- 102000009410 Chemokine receptor Human genes 0.000 title description 5
- 108050000299 Chemokine receptor Proteins 0.000 title description 5
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical class N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 365
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- 239000003814 drug Substances 0.000 claims abstract description 7
- 239000000543 intermediate Substances 0.000 claims description 272
- 125000000217 alkyl group Chemical group 0.000 claims description 185
- -1 aminocarbonyloxy Chemical group 0.000 claims description 167
- 238000000034 method Methods 0.000 claims description 112
- 229910052739 hydrogen Inorganic materials 0.000 claims description 66
- 239000001257 hydrogen Substances 0.000 claims description 61
- 125000001424 substituent group Chemical group 0.000 claims description 45
- 125000005843 halogen group Chemical group 0.000 claims description 43
- 125000003545 alkoxy group Chemical group 0.000 claims description 41
- 150000001412 amines Chemical class 0.000 claims description 37
- 125000000623 heterocyclic group Chemical group 0.000 claims description 36
- 125000004432 carbon atom Chemical group C* 0.000 claims description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- 229910052736 halogen Inorganic materials 0.000 claims description 23
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 21
- 150000002431 hydrogen Chemical class 0.000 claims description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
- 125000001072 heteroaryl group Chemical group 0.000 claims description 20
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- 125000003118 aryl group Chemical group 0.000 claims description 19
- 229910052799 carbon Inorganic materials 0.000 claims description 17
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 14
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 14
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
- 238000011282 treatment Methods 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 208000032064 Chronic Limb-Threatening Ischemia Diseases 0.000 claims description 10
- 206010034576 Peripheral ischaemia Diseases 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 230000008569 process Effects 0.000 claims description 8
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 7
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
- 125000005936 piperidyl group Chemical group 0.000 claims description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
- LYGOTSCQTCBTAN-HNAYVOBHSA-N (3s)-4-[3-chloro-4-(trifluoromethyl)phenyl]-1-[4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-4-oxobutyl]-3-methylpiperazin-2-one Chemical compound C=1C=C(C(F)(F)F)C(Cl)=CC=1N([C@H](C1=O)C)CCN1CCCC(=O)N(C[C@H]1O)CCC21CC2 LYGOTSCQTCBTAN-HNAYVOBHSA-N 0.000 claims description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 206010003178 Arterial thrombosis Diseases 0.000 claims description 5
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 claims description 5
- 206010063837 Reperfusion injury Diseases 0.000 claims description 5
- 239000013543 active substance Substances 0.000 claims description 5
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 5
- 125000000304 alkynyl group Chemical group 0.000 claims description 5
- 208000006673 asthma Diseases 0.000 claims description 5
- 230000007214 atherothrombosis Effects 0.000 claims description 5
- 206010012601 diabetes mellitus Diseases 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- 208000012947 ischemia reperfusion injury Diseases 0.000 claims description 5
- 201000006417 multiple sclerosis Diseases 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- BSCCSDNZEIHXOK-UHFFFAOYSA-N phenyl carbamate Chemical class NC(=O)OC1=CC=CC=C1 BSCCSDNZEIHXOK-UHFFFAOYSA-N 0.000 claims description 5
- 238000011321 prophylaxis Methods 0.000 claims description 5
- 208000037260 Atherosclerotic Plaque Diseases 0.000 claims description 4
- 208000031229 Cardiomyopathies Diseases 0.000 claims description 4
- 208000011231 Crohn disease Diseases 0.000 claims description 4
- 208000002249 Diabetes Complications Diseases 0.000 claims description 4
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 4
- 206010019280 Heart failures Diseases 0.000 claims description 4
- 208000007177 Left Ventricular Hypertrophy Diseases 0.000 claims description 4
- 208000006011 Stroke Diseases 0.000 claims description 4
- 208000025865 Ulcer Diseases 0.000 claims description 4
- MPVDXIMFBOLMNW-UHFFFAOYSA-N chembl1615565 Chemical compound OC1=CC=C2C=C(S(O)(=O)=O)C=C(S(O)(=O)=O)C2=C1N=NC1=CC=CC=C1 MPVDXIMFBOLMNW-UHFFFAOYSA-N 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 208000033679 diabetic kidney disease Diseases 0.000 claims description 4
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 4
- 208000004296 neuralgia Diseases 0.000 claims description 4
- 208000021722 neuropathic pain Diseases 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 208000037803 restenosis Diseases 0.000 claims description 4
- 230000001225 therapeutic effect Effects 0.000 claims description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
- 231100000397 ulcer Toxicity 0.000 claims description 4
- FMISICMVTKSRSR-QFBILLFUSA-N (2s)-4-[4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-4-oxobutyl]-2-methyl-3-oxo-n-[4-(trifluoromethyl)phenyl]piperazine-1-carboxamide Chemical compound C=1C=C(C(F)(F)F)C=CC=1NC(=O)N([C@H](C1=O)C)CCN1CCCC(=O)N(C[C@H]1O)CCC21CC2 FMISICMVTKSRSR-QFBILLFUSA-N 0.000 claims description 3
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 3
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 3
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 3
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 3
- 206010002388 Angina unstable Diseases 0.000 claims description 3
- 208000007814 Unstable Angina Diseases 0.000 claims description 3
- 125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 3
- 125000005002 aryl methyl group Chemical group 0.000 claims description 3
- 150000001602 bicycloalkyls Chemical group 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 201000004332 intermediate coronary syndrome Diseases 0.000 claims description 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- YIRTUHPVXLFTKK-PLMTUMEDSA-N (2r)-1-[3,4-bis(trifluoromethyl)phenyl]-4-[(2s)-1-hydroxy-5-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-5-oxopentan-2-yl]-2-methyl-1,4-diazepan-5-one Chemical compound C([C@@H](CO)N1C[C@H](N(CCC1=O)C=1C=C(C(=CC=1)C(F)(F)F)C(F)(F)F)C)CC(=O)N(C[C@H]1O)CCC21CC2 YIRTUHPVXLFTKK-PLMTUMEDSA-N 0.000 claims description 2
- AOVAASKPKQGDSJ-RWMBFGLXSA-N (3S,6S)-4-[4-[(8S)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-4-oxobutyl]-6-methyl-5-oxopiperazine-1,3-dicarboxylic acid Chemical compound O[C@H]1C2(CC2)CCN(C1)C(CCCN1[C@@H](CN([C@H](C1=O)C)C(=O)O)C(=O)O)=O AOVAASKPKQGDSJ-RWMBFGLXSA-N 0.000 claims description 2
- DQVWVRYEVWKJIM-ZOCIIQOWSA-N (3s,6s)-1-n-[3-chloro-4-(trifluoromethyl)phenyl]-4-[4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-4-oxobutyl]-6-methyl-5-oxopiperazine-1,3-dicarboxamide Chemical compound N1([C@@H](CN([C@H](C1=O)C)C(=O)NC=1C=C(Cl)C(=CC=1)C(F)(F)F)C(N)=O)CCCC(=O)N(C[C@H]1O)CCC21CC2 DQVWVRYEVWKJIM-ZOCIIQOWSA-N 0.000 claims description 2
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 claims description 2
- ZWVXFIRAOPYQTP-HWKANZROSA-N 1-[(e)-3-(3,4-dichlorophenyl)prop-2-enoyl]-4-[3-(4-hydroxy-4-methylpiperidin-1-yl)-3-oxopropyl]-1,4-diazepan-5-one Chemical compound C1CC(C)(O)CCN1C(=O)CCN1C(=O)CCN(C(=O)\C=C\C=2C=C(Cl)C(Cl)=CC=2)CC1 ZWVXFIRAOPYQTP-HWKANZROSA-N 0.000 claims description 2
- IUNCMBOVMROGNB-FXAWDEMLSA-N 1-[3-chloro-4-(trifluoromethyl)phenyl]-4-[(2s)-1-hydroxy-5-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-5-oxopentan-2-yl]-1,4-diazepan-5-one Chemical compound C([C@@H](CO)N1C(CCN(CC1)C=1C=C(Cl)C(=CC=1)C(F)(F)F)=O)CC(=O)N(C[C@H]1O)CCC21CC2 IUNCMBOVMROGNB-FXAWDEMLSA-N 0.000 claims description 2
- WYZZNMWIWHRXRM-UHFFFAOYSA-N 2,8-diazaspiro[4.5]decane Chemical compound C1NCCC21CCNCC2 WYZZNMWIWHRXRM-UHFFFAOYSA-N 0.000 claims description 2
- 206010012655 Diabetic complications Diseases 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 229910003827 NRaRb Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Chemical group 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims description 2
- GFLPYFFFAVWPKS-LJQANCHMSA-N n-[3-chloro-4-(trifluoromethyl)phenyl]-4-[4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-4-oxobutyl]-5-oxo-1,4-diazepane-1-carboxamide Chemical compound C([C@H]1O)N(C(=O)CCCN2C(CCN(CC2)C(=O)NC=2C=C(Cl)C(=CC=2)C(F)(F)F)=O)CCC11CC1 GFLPYFFFAVWPKS-LJQANCHMSA-N 0.000 claims description 2
- 125000004043 oxo group Chemical group O=* 0.000 claims description 2
- 239000000651 prodrug Substances 0.000 claims description 2
- 229940002612 prodrug Drugs 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 12
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 8
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims 2
- 239000005557 antagonist Substances 0.000 abstract description 8
- 102000004497 CCR2 Receptors Human genes 0.000 abstract description 6
- 108010017312 CCR2 Receptors Proteins 0.000 abstract description 6
- 102000004499 CCR3 Receptors Human genes 0.000 abstract description 2
- 108010017316 CCR3 Receptors Proteins 0.000 abstract description 2
- 102000004274 CCR5 Receptors Human genes 0.000 abstract description 2
- 108010017088 CCR5 Receptors Proteins 0.000 abstract description 2
- 125000002619 bicyclic group Chemical group 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 417
- 239000000243 solution Substances 0.000 description 263
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 253
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 221
- 238000006243 chemical reaction Methods 0.000 description 165
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 163
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 144
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 121
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 101
- 239000000203 mixture Substances 0.000 description 101
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 99
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 95
- 235000019439 ethyl acetate Nutrition 0.000 description 93
- 239000003921 oil Substances 0.000 description 92
- 235000019198 oils Nutrition 0.000 description 92
- 239000000460 chlorine Substances 0.000 description 89
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 87
- 239000011734 sodium Substances 0.000 description 81
- 239000006260 foam Substances 0.000 description 74
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 69
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 69
- 239000012074 organic phase Substances 0.000 description 67
- 239000007787 solid Substances 0.000 description 65
- 239000002904 solvent Substances 0.000 description 64
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 62
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 62
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 61
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 59
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 57
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 50
- 239000011780 sodium chloride Substances 0.000 description 47
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 42
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 41
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 40
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 39
- 239000002585 base Substances 0.000 description 39
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 39
- 229920006395 saturated elastomer Polymers 0.000 description 37
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 35
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 34
- 229910004298 SiO 2 Inorganic materials 0.000 description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- 238000000746 purification Methods 0.000 description 29
- 239000011541 reaction mixture Substances 0.000 description 29
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 29
- 239000000725 suspension Substances 0.000 description 29
- 235000017557 sodium bicarbonate Nutrition 0.000 description 28
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 25
- 230000002829 reductive effect Effects 0.000 description 25
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
- 239000002253 acid Substances 0.000 description 24
- 239000003153 chemical reaction reagent Substances 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 23
- UTLJTKFPIYWIRV-ZCFIWIBFSA-N (8s)-6-azaspiro[2.5]octan-8-ol Chemical compound O[C@@H]1CNCCC11CC1 UTLJTKFPIYWIRV-ZCFIWIBFSA-N 0.000 description 22
- 238000001816 cooling Methods 0.000 description 22
- 238000001556 precipitation Methods 0.000 description 22
- 239000000843 powder Substances 0.000 description 21
- 239000000741 silica gel Substances 0.000 description 21
- 229910002027 silica gel Inorganic materials 0.000 description 21
- 229960001866 silicon dioxide Drugs 0.000 description 21
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 20
- 239000012876 carrier material Substances 0.000 description 20
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 20
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 20
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 19
- 150000001408 amides Chemical class 0.000 description 19
- 238000001704 evaporation Methods 0.000 description 19
- 230000008020 evaporation Effects 0.000 description 19
- 238000003818 flash chromatography Methods 0.000 description 19
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 18
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 18
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 18
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 17
- 125000000753 cycloalkyl group Chemical group 0.000 description 17
- 150000002148 esters Chemical class 0.000 description 17
- 239000007788 liquid Substances 0.000 description 17
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 16
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 16
- 150000003335 secondary amines Chemical class 0.000 description 16
- 125000003647 acryloyl group Chemical group O=C([*])C([H])=C([H])[H] 0.000 description 15
- 239000000047 product Substances 0.000 description 14
- 239000012298 atmosphere Substances 0.000 description 13
- 238000001914 filtration Methods 0.000 description 13
- 229960004592 isopropanol Drugs 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
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- KZAMRRANXJVDCD-UHFFFAOYSA-N 3-chloro-4-(trifluoromethyl)aniline Chemical compound NC1=CC=C(C(F)(F)F)C(Cl)=C1 KZAMRRANXJVDCD-UHFFFAOYSA-N 0.000 description 11
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 11
- 235000010357 aspartame Nutrition 0.000 description 11
- 235000011121 sodium hydroxide Nutrition 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- 102100031151 C-C chemokine receptor type 2 Human genes 0.000 description 10
- 101710149815 C-C chemokine receptor type 2 Proteins 0.000 description 10
- 239000007821 HATU Substances 0.000 description 10
- 150000001299 aldehydes Chemical class 0.000 description 10
- 239000000010 aprotic solvent Substances 0.000 description 10
- 230000003197 catalytic effect Effects 0.000 description 10
- 150000002576 ketones Chemical class 0.000 description 10
- AZBSPWGJIGOKAB-NSHDSACASA-N methyl (2s)-2-[2-oxoethyl(phenylmethoxycarbonyl)amino]propanoate Chemical compound COC(=O)[C@H](C)N(CC=O)C(=O)OCC1=CC=CC=C1 AZBSPWGJIGOKAB-NSHDSACASA-N 0.000 description 10
- 239000000546 pharmaceutical excipient Substances 0.000 description 10
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 10
- RMFCIPWFVQRFRC-QWHCGFSZSA-N (3s)-1-[4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-4-oxobutyl]-3-methylpiperazin-2-one Chemical compound O=C1[C@H](C)NCCN1CCCC(=O)N1C[C@@H](O)C2(CC2)CC1 RMFCIPWFVQRFRC-QWHCGFSZSA-N 0.000 description 9
- FGOJCPKOOGIRPA-UHFFFAOYSA-N 1-o-tert-butyl 4-o-ethyl 5-oxoazepane-1,4-dicarboxylate Chemical compound CCOC(=O)C1CCN(C(=O)OC(C)(C)C)CCC1=O FGOJCPKOOGIRPA-UHFFFAOYSA-N 0.000 description 9
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 9
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 239000013078 crystal Substances 0.000 description 9
- 238000010511 deprotection reaction Methods 0.000 description 9
- 229960004132 diethyl ether Drugs 0.000 description 9
- 150000004820 halides Chemical class 0.000 description 9
- 238000005984 hydrogenation reaction Methods 0.000 description 9
- 230000007062 hydrolysis Effects 0.000 description 9
- 238000006460 hydrolysis reaction Methods 0.000 description 9
- 230000003647 oxidation Effects 0.000 description 9
- 238000007254 oxidation reaction Methods 0.000 description 9
- 229940095574 propionic acid Drugs 0.000 description 9
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
- 229910052938 sodium sulfate Inorganic materials 0.000 description 9
- 235000011152 sodium sulphate Nutrition 0.000 description 9
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 8
- PSDVFXQQNBDDJC-UHFFFAOYSA-N 3,4-bis(trifluoromethyl)aniline Chemical compound NC1=CC=C(C(F)(F)F)C(C(F)(F)F)=C1 PSDVFXQQNBDDJC-UHFFFAOYSA-N 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 239000001828 Gelatine Substances 0.000 description 8
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 8
- 235000019502 Orange oil Nutrition 0.000 description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 8
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- 239000002775 capsule Substances 0.000 description 8
- 150000001721 carbon Chemical group 0.000 description 8
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 8
- 229910052801 chlorine Inorganic materials 0.000 description 8
- 238000005859 coupling reaction Methods 0.000 description 8
- 229920000159 gelatin Polymers 0.000 description 8
- 235000019322 gelatine Nutrition 0.000 description 8
- 229910052744 lithium Inorganic materials 0.000 description 8
- 239000010502 orange oil Substances 0.000 description 8
- 229910052763 palladium Inorganic materials 0.000 description 8
- 239000000825 pharmaceutical preparation Substances 0.000 description 8
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 8
- 229920005862 polyol Polymers 0.000 description 8
- 150000003077 polyols Chemical class 0.000 description 8
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 8
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 8
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 8
- 125000006239 protecting group Chemical group 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 238000000926 separation method Methods 0.000 description 8
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- QPPLBCQXWDBQFS-UHFFFAOYSA-N 1,4-diazepan-5-one Chemical compound O=C1CCNCCN1 QPPLBCQXWDBQFS-UHFFFAOYSA-N 0.000 description 7
- QBMAFROYRRIETJ-VIFPVBQESA-N 3-[(3s)-4-[(3,4-dichlorophenyl)carbamoyl]-3-methyl-2-oxopiperazin-1-yl]propanoic acid Chemical compound C1CN(CCC(O)=O)C(=O)[C@H](C)N1C(=O)NC1=CC=C(Cl)C(Cl)=C1 QBMAFROYRRIETJ-VIFPVBQESA-N 0.000 description 7
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 7
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 7
- 238000012369 In process control Methods 0.000 description 7
- 239000005708 Sodium hypochlorite Substances 0.000 description 7
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 7
- 239000012346 acetyl chloride Substances 0.000 description 7
- 150000001414 amino alcohols Chemical class 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 150000004702 methyl esters Chemical class 0.000 description 7
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
- 238000006268 reductive amination reaction Methods 0.000 description 7
- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 7
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
- CCEHRLJYWYVRLY-ZSZQSSIHSA-N (2s)-n-[3,4-bis(trifluoromethyl)phenyl]-4-[(2r)-2-hydroxy-4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-4-oxobutyl]-2-methyl-3-oxopiperazine-1-carboxamide Chemical compound C([C@@H](O)CN1CCN([C@H](C1=O)C)C(=O)NC=1C=C(C(=CC=1)C(F)(F)F)C(F)(F)F)C(=O)N(C[C@H]1O)CCC21CC2 CCEHRLJYWYVRLY-ZSZQSSIHSA-N 0.000 description 6
- LYGOTSCQTCBTAN-DNVCBOLYSA-N (3r)-4-[3-chloro-4-(trifluoromethyl)phenyl]-1-[4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-4-oxobutyl]-3-methylpiperazin-2-one Chemical compound C=1C=C(C(F)(F)F)C(Cl)=CC=1N([C@@H](C1=O)C)CCN1CCCC(=O)N(C[C@H]1O)CCC21CC2 LYGOTSCQTCBTAN-DNVCBOLYSA-N 0.000 description 6
- YMNMPPFWKKFPQJ-HNAYVOBHSA-N (3s)-4-[4-chloro-3-(trifluoromethoxy)phenyl]-1-[4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-4-oxobutyl]-3-methylpiperazin-2-one Chemical compound C=1C=C(Cl)C(OC(F)(F)F)=CC=1N([C@H](C1=O)C)CCN1CCCC(=O)N(C[C@H]1O)CCC21CC2 YMNMPPFWKKFPQJ-HNAYVOBHSA-N 0.000 description 6
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 6
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 6
- GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 description 6
- 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 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 6
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 6
- 229910052794 bromium Inorganic materials 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 238000000605 extraction Methods 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 6
- 238000004190 ion pair chromatography Methods 0.000 description 6
- 239000012948 isocyanate Substances 0.000 description 6
- 150000002513 isocyanates Chemical class 0.000 description 6
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 235000011181 potassium carbonates Nutrition 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 6
- 239000001993 wax Substances 0.000 description 6
- KSLULJPDIQUDAO-HNAYVOBHSA-N (2s)-n-(3,4-dichlorophenyl)-4-[4-[(3s)-3-hydroxy-4,4-dimethylpiperidin-1-yl]-4-oxobutyl]-2-methyl-3-oxopiperazine-1-carboxamide Chemical compound C=1C=C(Cl)C(Cl)=CC=1NC(=O)N([C@H](C1=O)C)CCN1CCCC(=O)N1CCC(C)(C)[C@H](O)C1 KSLULJPDIQUDAO-HNAYVOBHSA-N 0.000 description 5
- RBMFUSZZXTXMTD-ZSZQSSIHSA-N (2s)-n-[3-chloro-4-(trifluoromethyl)phenyl]-4-[(2r)-2-hydroxy-4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-4-oxobutyl]-2-methyl-3-oxopiperazine-1-carboxamide Chemical compound C([C@@H](O)CN1CCN([C@H](C1=O)C)C(=O)NC=1C=C(Cl)C(=CC=1)C(F)(F)F)C(=O)N(C[C@H]1O)CCC21CC2 RBMFUSZZXTXMTD-ZSZQSSIHSA-N 0.000 description 5
- HTJFERSPZLONLM-DUXPYHPUSA-N 1-[(e)-3-(3,4-dichlorophenyl)prop-2-enoyl]-1,4-diazepan-5-one Chemical compound C1=C(Cl)C(Cl)=CC=C1\C=C\C(=O)N1CCC(=O)NCC1 HTJFERSPZLONLM-DUXPYHPUSA-N 0.000 description 5
- QWXAYHAPQNMAKI-UHFFFAOYSA-N 2-chloro-4-isocyanato-1-(trifluoromethoxy)benzene Chemical compound FC(F)(F)OC1=CC=C(N=C=O)C=C1Cl QWXAYHAPQNMAKI-UHFFFAOYSA-N 0.000 description 5
- HCWZJEXQULSHSD-UHFFFAOYSA-N 2-chloro-4-isocyanato-1-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(N=C=O)C=C1Cl HCWZJEXQULSHSD-UHFFFAOYSA-N 0.000 description 5
- MFUVCHZWGSJKEQ-UHFFFAOYSA-N 3,4-dichlorphenylisocyanate Chemical compound ClC1=CC=C(N=C=O)C=C1Cl MFUVCHZWGSJKEQ-UHFFFAOYSA-N 0.000 description 5
- ZPKUUNGPBSRPRM-UHFFFAOYSA-N 3-chloro-4-(trifluoromethoxy)aniline Chemical compound NC1=CC=C(OC(F)(F)F)C(Cl)=C1 ZPKUUNGPBSRPRM-UHFFFAOYSA-N 0.000 description 5
- QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 5
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 5
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 5
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 5
- 230000029936 alkylation Effects 0.000 description 5
- 238000005804 alkylation reaction Methods 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 230000027455 binding Effects 0.000 description 5
- 230000008878 coupling Effects 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 230000002757 inflammatory effect Effects 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 5
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 5
- 238000002953 preparative HPLC Methods 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- MQOLTEHTFKRZNV-UHFFFAOYSA-N tert-butyl 8-hydroxy-6-azaspiro[2.5]octane-6-carboxylate Chemical compound OC1CN(C(=O)OC(C)(C)C)CCC11CC1 MQOLTEHTFKRZNV-UHFFFAOYSA-N 0.000 description 5
- UCGIBIIHRXRKHW-UHFFFAOYSA-N tert-butyl 8-oxo-6-azaspiro[2.5]octane-6-carboxylate Chemical compound O=C1CN(C(=O)OC(C)(C)C)CCC11CC1 UCGIBIIHRXRKHW-UHFFFAOYSA-N 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- HQPGHJDPMYJKDA-URLQWDBASA-N (2s)-n-[3-chloro-4-(trifluoromethoxy)phenyl]-4-[(2s)-2-hydroxy-4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-4-oxobutyl]-2-methyl-3-oxopiperazine-1-carboxamide Chemical compound C([C@H](O)CN1CCN([C@H](C1=O)C)C(=O)NC=1C=C(Cl)C(OC(F)(F)F)=CC=1)C(=O)N(C[C@H]1O)CCC21CC2 HQPGHJDPMYJKDA-URLQWDBASA-N 0.000 description 4
- QRPFDHNPAQMATF-DNVCBOLYSA-N (3r)-4-(3,4-dichlorophenyl)-1-[4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-4-oxobutyl]-3-methylpiperazin-2-one Chemical compound C=1C=C(Cl)C(Cl)=CC=1N([C@@H](C1=O)C)CCN1CCCC(=O)N(C[C@H]1O)CCC21CC2 QRPFDHNPAQMATF-DNVCBOLYSA-N 0.000 description 4
- PKFOEIVIFRQCLD-GEMLJDPKSA-N (3s,5s)-5-methylpiperidin-3-ol;hydrochloride Chemical compound Cl.C[C@@H]1CNC[C@@H](O)C1 PKFOEIVIFRQCLD-GEMLJDPKSA-N 0.000 description 4
- SAXIQCMTXJWCIK-DUXPYHPUSA-N 1-[(e)-3-(3,4-dichlorophenyl)prop-2-enoyl]-4-(2-oxooxolan-3-yl)-1,4-diazepan-5-one Chemical compound C1=C(Cl)C(Cl)=CC=C1\C=C\C(=O)N1CCC(=O)N(C2C(OCC2)=O)CC1 SAXIQCMTXJWCIK-DUXPYHPUSA-N 0.000 description 4
- OGFKTAMJLKHRAZ-UHFFFAOYSA-N 2,2-dimethoxyacetaldehyde Chemical compound COC(OC)C=O OGFKTAMJLKHRAZ-UHFFFAOYSA-N 0.000 description 4
- JTTKDJDISQAFJL-HWKANZROSA-N 3-[4-[(e)-3-(3,4-dichlorophenyl)prop-2-enoyl]-7-oxo-1,4-diazepan-1-yl]-4-methoxy-4-oxobutanoic acid Chemical compound C1CC(=O)N(C(CC(O)=O)C(=O)OC)CCN1C(=O)\C=C\C1=CC=C(Cl)C(Cl)=C1 JTTKDJDISQAFJL-HWKANZROSA-N 0.000 description 4
- CQLBBVQRMIPKQM-DUXPYHPUSA-N 3-[4-[(e)-3-(3,4-dichlorophenyl)prop-2-enoyl]-7-oxo-1,4-diazepan-1-yl]propanoic acid Chemical compound C1CC(=O)N(CCC(=O)O)CCN1C(=O)\C=C\C1=CC=C(Cl)C(Cl)=C1 CQLBBVQRMIPKQM-DUXPYHPUSA-N 0.000 description 4
- QKSZDUBKSCBXDB-NSHDSACASA-N 4-[(3s)-4-[(3-chlorophenyl)carbamoyl]-3-methyl-2-oxopiperazin-1-yl]butanoic acid Chemical compound C1CN(CCCC(O)=O)C(=O)[C@H](C)N1C(=O)NC1=CC=CC(Cl)=C1 QKSZDUBKSCBXDB-NSHDSACASA-N 0.000 description 4
- SODLPCCEKPQWAY-UHFFFAOYSA-N 5-methylpiperazin-2-one Chemical compound CC1CNC(=O)CN1 SODLPCCEKPQWAY-UHFFFAOYSA-N 0.000 description 4
- 102000019034 Chemokines Human genes 0.000 description 4
- 108010012236 Chemokines Proteins 0.000 description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
- 239000004129 EU approved improving agent Substances 0.000 description 4
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 4
- 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 4
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 4
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- 125000002947 alkylene group Chemical group 0.000 description 4
- 208000026935 allergic disease Diseases 0.000 description 4
- 229940024606 amino acid Drugs 0.000 description 4
- 239000012131 assay buffer Substances 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- 230000002210 biocatalytic effect Effects 0.000 description 4
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 4
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 4
- 150000003857 carboxamides Chemical class 0.000 description 4
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 4
- 239000007822 coupling agent Substances 0.000 description 4
- 230000005595 deprotonation Effects 0.000 description 4
- 238000010537 deprotonation reaction Methods 0.000 description 4
- 239000003925 fat Substances 0.000 description 4
- 125000005456 glyceride group Chemical group 0.000 description 4
- 208000027866 inflammatory disease Diseases 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 150000002596 lactones Chemical class 0.000 description 4
- OGLNPRJAZLSAPD-MELADBBJSA-N methyl (2s)-5-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-2-[(3s)-3-methyl-2-oxopiperazin-1-yl]-5-oxopentanoate Chemical compound C([C@@H](C(=O)OC)N1C([C@H](C)NCC1)=O)CC(=O)N(C[C@H]1O)CCC21CC2 OGLNPRJAZLSAPD-MELADBBJSA-N 0.000 description 4
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 4
- 235000019796 monopotassium phosphate Nutrition 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 150000003254 radicals Chemical class 0.000 description 4
- 230000000717 retained effect Effects 0.000 description 4
- 125000006413 ring segment Chemical group 0.000 description 4
- VFWRGKJLLYDFBY-UHFFFAOYSA-N silver;hydrate Chemical compound O.[Ag].[Ag] VFWRGKJLLYDFBY-UHFFFAOYSA-N 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 4
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000000829 suppository Substances 0.000 description 4
- JPMWJZFRRFCRDY-UHFFFAOYSA-N tert-butyl 4-(2,2-dimethoxyethylamino)butanoate Chemical compound COC(OC)CNCCCC(=O)OC(C)(C)C JPMWJZFRRFCRDY-UHFFFAOYSA-N 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 235000015112 vegetable and seed oil Nutrition 0.000 description 4
- 239000008158 vegetable oil Substances 0.000 description 4
- GPEODOFMOAIVMT-YFKPBYRVSA-N (2s)-2-[3-chloro-4-(trifluoromethyl)anilino]propanoic acid Chemical compound OC(=O)[C@H](C)NC1=CC=C(C(F)(F)F)C(Cl)=C1 GPEODOFMOAIVMT-YFKPBYRVSA-N 0.000 description 3
- GXHUQTFYXMETMF-RWMBFGLXSA-N (3s)-1-[(2s)-2-hydroxy-4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-4-oxobutyl]-3-methylpiperazin-2-one Chemical compound O=C1[C@H](C)NCCN1C[C@@H](O)CC(=O)N1C[C@@H](O)C2(CC2)CC1 GXHUQTFYXMETMF-RWMBFGLXSA-N 0.000 description 3
- YPDSIELNQNQORJ-UONOGXRCSA-N (3s)-1-[4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-3,3-dimethyl-4-oxobutyl]-3-methylpiperazin-2-one Chemical compound O=C1[C@H](C)NCCN1CCC(C)(C)C(=O)N1C[C@@H](O)C2(CC2)CC1 YPDSIELNQNQORJ-UONOGXRCSA-N 0.000 description 3
- RSOONMAOICLYIW-UONOGXRCSA-N (3s)-1-[5-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-5-oxopentyl]-3-methylpiperazin-2-one Chemical compound O=C1[C@H](C)NCCN1CCCCC(=O)N1C[C@@H](O)C2(CC2)CC1 RSOONMAOICLYIW-UONOGXRCSA-N 0.000 description 3
- GZSCYLJBBWUCBZ-RIHPBJNCSA-N (3s,4s)-4-methylpiperidin-3-ol;hydrochloride Chemical compound Cl.C[C@H]1CCNC[C@H]1O GZSCYLJBBWUCBZ-RIHPBJNCSA-N 0.000 description 3
- LQHLLGBMPQNQLJ-NSHDSACASA-N (5s)-1-benzyl-5-methylpiperidin-3-one Chemical compound C1C(=O)C[C@H](C)CN1CC1=CC=CC=C1 LQHLLGBMPQNQLJ-NSHDSACASA-N 0.000 description 3
- LGPKFIGMLPDYEA-UHFFFAOYSA-N 1-isocyanato-4-(trifluoromethoxy)benzene Chemical compound FC(F)(F)OC1=CC=C(N=C=O)C=C1 LGPKFIGMLPDYEA-UHFFFAOYSA-N 0.000 description 3
- KJCIMSSFGUGTGA-UHFFFAOYSA-N 1-methylpiperazin-2-one Chemical compound CN1CCNCC1=O KJCIMSSFGUGTGA-UHFFFAOYSA-N 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- OZIYUZINTQIIAN-UHFFFAOYSA-N 2-[4-[6-bromo-3-(butylamino)imidazo[1,2-a]pyridin-2-yl]phenoxy]acetic acid Chemical compound N1=C2C=CC(Br)=CN2C(NCCCC)=C1C1=CC=C(OCC(O)=O)C=C1 OZIYUZINTQIIAN-UHFFFAOYSA-N 0.000 description 3
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 3
- SDYWXFYBZPNOFX-UHFFFAOYSA-N 3,4-dichloroaniline Chemical compound NC1=CC=C(Cl)C(Cl)=C1 SDYWXFYBZPNOFX-UHFFFAOYSA-N 0.000 description 3
- ULKOSOBERDYUKP-URWSZGRFSA-N 3-[(3r)-4-[(e)-3-(3-chlorophenyl)prop-2-enoyl]-3-methyl-7-oxo-1,4-diazepan-1-yl]propanoic acid Chemical compound C[C@@H]1CN(CCC(O)=O)C(=O)CCN1C(=O)\C=C\C1=CC=CC(Cl)=C1 ULKOSOBERDYUKP-URWSZGRFSA-N 0.000 description 3
- GVHVGOBZKOMQHZ-AATRIKPKSA-N 3-[4-[(e)-3-(3-chlorophenyl)prop-2-enoyl]-7-oxo-1,4-diazepan-1-yl]-4-methoxy-4-oxobutanoic acid Chemical compound C1CC(=O)N(C(CC(O)=O)C(=O)OC)CCN1C(=O)\C=C\C1=CC=CC(Cl)=C1 GVHVGOBZKOMQHZ-AATRIKPKSA-N 0.000 description 3
- PNPCRKVUWYDDST-UHFFFAOYSA-N 3-chloroaniline Chemical compound NC1=CC=CC(Cl)=C1 PNPCRKVUWYDDST-UHFFFAOYSA-N 0.000 description 3
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 3
- FLTVPEOIHLTCQZ-LLVKDONJSA-N 4-[(3r)-4-[3-chloro-4-(trifluoromethyl)phenyl]-3-methyl-7-oxo-2,3-dihydro-1,4-diazepin-1-yl]butanoic acid Chemical compound C[C@@H]1CN(CCCC(O)=O)C(=O)C=CN1C1=CC=C(C(F)(F)F)C(Cl)=C1 FLTVPEOIHLTCQZ-LLVKDONJSA-N 0.000 description 3
- XTUZYUOVMCIDRP-CYBMUJFWSA-N 4-[4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-4-oxobutyl]-1,4-diazepan-5-one Chemical compound C([C@H]1O)N(C(=O)CCCN2C(CCNCC2)=O)CCC11CC1 XTUZYUOVMCIDRP-CYBMUJFWSA-N 0.000 description 3
- CXBLQEIODBBSQD-UHFFFAOYSA-N 4-methylpiperidin-4-ol Chemical compound CC1(O)CCNCC1 CXBLQEIODBBSQD-UHFFFAOYSA-N 0.000 description 3
- GSOUVFPKNXCPEN-CMDGGOBGSA-N 4-o-tert-butyl 1-o-methyl 2-[4-[(e)-3-(3-chlorophenyl)prop-2-enoyl]-7-oxo-1,4-diazepan-1-yl]butanedioate Chemical compound C1CC(=O)N(C(CC(=O)OC(C)(C)C)C(=O)OC)CCN1C(=O)\C=C\C1=CC=CC(Cl)=C1 GSOUVFPKNXCPEN-CMDGGOBGSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 description 3
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 description 3
- 206010007559 Cardiac failure congestive Diseases 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
- 101001110310 Lentilactobacillus kefiri NADP-dependent (R)-specific alcohol dehydrogenase Proteins 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 150000001263 acyl chlorides Chemical class 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- 150000001350 alkyl halides Chemical class 0.000 description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- 235000011114 ammonium hydroxide Nutrition 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 150000004982 aromatic amines Chemical class 0.000 description 3
- FCKGYYKPQHCNMY-INIZCTEOSA-N benzyl (2s)-2-methyl-4-[4-[(2-methylpropan-2-yl)oxy]-4-oxobutyl]-3-oxopiperazine-1-carboxylate Chemical compound C1CN(CCCC(=O)OC(C)(C)C)C(=O)[C@H](C)N1C(=O)OCC1=CC=CC=C1 FCKGYYKPQHCNMY-INIZCTEOSA-N 0.000 description 3
- DFAYENFQBCMVCC-ZFWWWQNUSA-N benzyl (2s)-4-[(2s)-2-hydroxy-4-methoxy-4-oxobutyl]-2-methyl-3-oxopiperazine-1-carboxylate Chemical compound C[C@H]1C(=O)N(C[C@@H](O)CC(=O)OC)CCN1C(=O)OCC1=CC=CC=C1 DFAYENFQBCMVCC-ZFWWWQNUSA-N 0.000 description 3
- OCAPXZCHUACEEO-AZUAARDMSA-N benzyl (2s)-4-[4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-4-oxobutyl]-2-methyl-3-oxopiperazine-1-carboxylate Chemical compound C=1C=CC=CC=1COC(=O)N([C@H](C1=O)C)CCN1CCCC(=O)N(C[C@H]1O)CCC21CC2 OCAPXZCHUACEEO-AZUAARDMSA-N 0.000 description 3
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 3
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 150000001851 cinnamic acid derivatives Chemical class 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- 229940125890 compound Ia Drugs 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 3
- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 3
- ARFLASKVLJTEJD-UHFFFAOYSA-N ethyl 2-bromopropanoate Chemical compound CCOC(=O)C(C)Br ARFLASKVLJTEJD-UHFFFAOYSA-N 0.000 description 3
- 239000012065 filter cake Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 3
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 3
- 150000002540 isothiocyanates Chemical class 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- GPBDCFUQRMZDEX-ZAAXVRCTSA-N methyl (2s)-2-[(3s)-4-[[3-chloro-4-(trifluoromethoxy)phenyl]carbamoyl]-3-methyl-2-oxopiperazin-1-yl]-5-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-5-oxopentanoate Chemical compound C([C@@H](C(=O)OC)N1C([C@H](C)N(CC1)C(=O)NC=1C=C(Cl)C(OC(F)(F)F)=CC=1)=O)CC(=O)N(C[C@H]1O)CCC21CC2 GPBDCFUQRMZDEX-ZAAXVRCTSA-N 0.000 description 3
- QUTSKIWJUHDULC-BYPYZUCNSA-N methyl (3s)-4-amino-3-hydroxybutanoate Chemical compound COC(=O)C[C@H](O)CN QUTSKIWJUHDULC-BYPYZUCNSA-N 0.000 description 3
- IXAVEKGUZAMWCV-HWKANZROSA-N methyl 2-[4-[(e)-3-(3,4-dichlorophenyl)prop-2-enoyl]-7-oxo-1,4-diazepan-1-yl]-4-hydroxybutanoate Chemical compound C1CC(=O)N(C(CCO)C(=O)OC)CCN1C(=O)\C=C\C1=CC=C(Cl)C(Cl)=C1 IXAVEKGUZAMWCV-HWKANZROSA-N 0.000 description 3
- WPCBLGLTQAQVAG-UHFFFAOYSA-N methyl 4-[tert-butyl(dimethyl)silyl]oxy-2-iodobutanoate Chemical compound COC(=O)C(I)CCO[Si](C)(C)C(C)(C)C WPCBLGLTQAQVAG-UHFFFAOYSA-N 0.000 description 3
- 239000002808 molecular sieve Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 3
- MXQOYLRVSVOCQT-UHFFFAOYSA-N palladium;tritert-butylphosphane Chemical compound [Pd].CC(C)(C)P(C(C)(C)C)C(C)(C)C.CC(C)(C)P(C(C)(C)C)C(C)(C)C MXQOYLRVSVOCQT-UHFFFAOYSA-N 0.000 description 3
- BIWOSRSKDCZIFM-UHFFFAOYSA-N piperidin-3-ol Chemical compound OC1CCCNC1 BIWOSRSKDCZIFM-UHFFFAOYSA-N 0.000 description 3
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 3
- 239000011736 potassium bicarbonate Substances 0.000 description 3
- 235000015497 potassium bicarbonate Nutrition 0.000 description 3
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 3
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 3
- 235000019260 propionic acid Nutrition 0.000 description 3
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 3
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 235000009518 sodium iodide Nutrition 0.000 description 3
- CDPOAAXJDYXYCR-UHFFFAOYSA-N spiro[2.5]octan-8-ol Chemical compound OC1CCCCC11CC1 CDPOAAXJDYXYCR-UHFFFAOYSA-N 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 3
- PRGPJAYLFPJVNB-VIFPVBQESA-N tert-butyl 3-[(3s)-3-methyl-2-oxopiperazin-1-yl]propanoate Chemical compound C[C@@H]1NCCN(CCC(=O)OC(C)(C)C)C1=O PRGPJAYLFPJVNB-VIFPVBQESA-N 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 3
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 3
- 235000019798 tripotassium phosphate Nutrition 0.000 description 3
- FOWGSQFSLNWXAU-ZCFIWIBFSA-N (2r)-2-[3-chloro-4-(trifluoromethyl)anilino]propan-1-ol Chemical compound OC[C@@H](C)NC1=CC=C(C(F)(F)F)C(Cl)=C1 FOWGSQFSLNWXAU-ZCFIWIBFSA-N 0.000 description 2
- OZHZDLFHFPTFNF-RXMQYKEDSA-N (2r)-2-[4-chloro-3-(trifluoromethyl)anilino]propanoic acid Chemical compound OC(=O)[C@@H](C)NC1=CC=C(Cl)C(C(F)(F)F)=C1 OZHZDLFHFPTFNF-RXMQYKEDSA-N 0.000 description 2
- APFBNYGUFPMFAU-YFKPBYRVSA-N (2s)-2-[4-chloro-3-(trifluoromethoxy)anilino]propanoic acid Chemical compound OC(=O)[C@H](C)NC1=CC=C(Cl)C(OC(F)(F)F)=C1 APFBNYGUFPMFAU-YFKPBYRVSA-N 0.000 description 2
- ZBWZXAAZBDUXCQ-QFBILLFUSA-N (2s)-n-(3-chlorophenyl)-4-[4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-4-oxobutyl]-2-methyl-3-oxopiperazine-1-carboxamide Chemical compound C=1C=CC(Cl)=CC=1NC(=O)N([C@H](C1=O)C)CCN1CCCC(=O)N(C[C@H]1O)CCC21CC2 ZBWZXAAZBDUXCQ-QFBILLFUSA-N 0.000 description 2
- AFVLOCGHBVXANG-RIFZZMRRSA-N (2s)-n-[3-chloro-4-(trifluoromethoxy)phenyl]-4-[(2s)-1-hydroxy-5-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-5-oxopentan-2-yl]-2-methyl-3-oxopiperazine-1-carboxamide Chemical compound C([C@@H](CO)N1CCN([C@H](C1=O)C)C(=O)NC=1C=C(Cl)C(OC(F)(F)F)=CC=1)CC(=O)N(C[C@H]1O)CCC21CC2 AFVLOCGHBVXANG-RIFZZMRRSA-N 0.000 description 2
- NUTXLGLIASBFFS-RIFZZMRRSA-N (2s)-n-[3-chloro-4-(trifluoromethyl)phenyl]-4-[(2s)-1-hydroxy-5-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-5-oxopentan-2-yl]-2-methyl-3-oxopiperazine-1-carboxamide Chemical compound C([C@@H](CO)N1CCN([C@H](C1=O)C)C(=O)NC=1C=C(Cl)C(=CC=1)C(F)(F)F)CC(=O)N(C[C@H]1O)CCC21CC2 NUTXLGLIASBFFS-RIFZZMRRSA-N 0.000 description 2
- JJYADPXATGSFSR-SOUVJXGZSA-N (3s)-1-[(2s)-5-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-1-methoxy-5-oxopentan-2-yl]-3-methylpiperazin-2-one Chemical compound C([C@@H](COC)N1C([C@H](C)NCC1)=O)CC(=O)N(C[C@H]1O)CCC21CC2 JJYADPXATGSFSR-SOUVJXGZSA-N 0.000 description 2
- BDFRGKVRUVWUBX-RWMBFGLXSA-N (3s)-1-[(3s)-3-hydroxy-4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-4-oxobutyl]-3-methylpiperazin-2-one Chemical compound O=C1[C@H](C)NCCN1CC[C@H](O)C(=O)N1C[C@@H](O)C2(CC2)CC1 BDFRGKVRUVWUBX-RWMBFGLXSA-N 0.000 description 2
- DHWIVOARSUSQLL-QWHCGFSZSA-N (3s)-1-[4-[(3s)-3-hydroxy-4,4-dimethylpiperidin-1-yl]-4-oxobutyl]-3-methylpiperazin-2-one Chemical compound O=C1[C@H](C)NCCN1CCCC(=O)N1C[C@@H](O)C(C)(C)CC1 DHWIVOARSUSQLL-QWHCGFSZSA-N 0.000 description 2
- BGJGKZMFNWQQQX-JSGCOSHPSA-N (3s)-3-hydroxy-4-[(3s)-3-methyl-2-oxo-4-phenylmethoxycarbonylpiperazin-1-yl]butanoic acid Chemical compound C1CN(C[C@@H](O)CC(O)=O)C(=O)[C@H](C)N1C(=O)OCC1=CC=CC=C1 BGJGKZMFNWQQQX-JSGCOSHPSA-N 0.000 description 2
- QRPFDHNPAQMATF-HNAYVOBHSA-N (3s)-4-(3,4-dichlorophenyl)-1-[4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-4-oxobutyl]-3-methylpiperazin-2-one Chemical compound C=1C=C(Cl)C(Cl)=CC=1N([C@H](C1=O)C)CCN1CCCC(=O)N(C[C@H]1O)CCC21CC2 QRPFDHNPAQMATF-HNAYVOBHSA-N 0.000 description 2
- ZRAXHSINYJDKEI-ONGXEEELSA-N (3s)-4-[(3s)-4-[3-chloro-4-(trifluoromethyl)phenyl]-3-methyl-2-oxopiperazin-1-yl]-3-hydroxybutanoic acid Chemical compound C1CN(C[C@@H](O)CC(O)=O)C(=O)[C@H](C)N1C1=CC=C(C(F)(F)F)C(Cl)=C1 ZRAXHSINYJDKEI-ONGXEEELSA-N 0.000 description 2
- TYBAGQDVWZJZKD-BVIVKCGYSA-N (3s)-4-[(e)-3-(3-chloro-4-fluorophenyl)prop-2-enoyl]-1-[3-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-3-oxopropyl]-3-methylpiperazin-2-one Chemical compound C=1C=C(F)C(Cl)=CC=1/C=C/C(=O)N([C@H](C1=O)C)CCN1CCC(=O)N(C[C@H]1O)CCC21CC2 TYBAGQDVWZJZKD-BVIVKCGYSA-N 0.000 description 2
- WPGPRLVPWACBHW-UHFFFAOYSA-N (4-methoxy-4-oxobutyl)azanium;chloride Chemical compound Cl.COC(=O)CCCN WPGPRLVPWACBHW-UHFFFAOYSA-N 0.000 description 2
- UPMISYJRXQVJQE-DZGCQCFKSA-N (4r)-5-methoxy-4-[(3s)-3-methyl-2-oxo-4-phenylmethoxycarbonylpiperazin-1-yl]-5-oxopentanoic acid Chemical compound C[C@H]1C(=O)N([C@H](CCC(O)=O)C(=O)OC)CCN1C(=O)OCC1=CC=CC=C1 UPMISYJRXQVJQE-DZGCQCFKSA-N 0.000 description 2
- SEQSGKFVRKVWNN-AAEUAGOBSA-N (4s)-4-[(3s)-4-[3-chloro-4-(trifluoromethyl)phenyl]-3-methyl-2-oxopiperazin-1-yl]-5-methoxypentanoic acid Chemical compound C[C@H]1C(=O)N([C@@H](CCC(O)=O)COC)CCN1C1=CC=C(C(F)(F)F)C(Cl)=C1 SEQSGKFVRKVWNN-AAEUAGOBSA-N 0.000 description 2
- UPMISYJRXQVJQE-ZFWWWQNUSA-N (4s)-5-methoxy-4-[(3s)-3-methyl-2-oxo-4-phenylmethoxycarbonylpiperazin-1-yl]-5-oxopentanoic acid Chemical compound C[C@H]1C(=O)N([C@@H](CCC(O)=O)C(=O)OC)CCN1C(=O)OCC1=CC=CC=C1 UPMISYJRXQVJQE-ZFWWWQNUSA-N 0.000 description 2
- JPADVSRUQWYWLD-HOCLYGCPSA-N (4s)-5-methoxy-4-[(3s)-3-methyl-2-oxo-4-phenylmethoxycarbonylpiperazin-1-yl]pentanoic acid Chemical compound C[C@H]1C(=O)N([C@@H](CCC(O)=O)COC)CCN1C(=O)OCC1=CC=CC=C1 JPADVSRUQWYWLD-HOCLYGCPSA-N 0.000 description 2
- BKVWWBSIILYIBZ-FYZOBXCZSA-N (8s)-6-azaspiro[2.5]octan-8-ol;hydrochloride Chemical compound Cl.O[C@@H]1CNCCC11CC1 BKVWWBSIILYIBZ-FYZOBXCZSA-N 0.000 description 2
- JWSLQKOQLDDQHH-CYBMUJFWSA-N (8s)-6-benzyl-6-azaspiro[2.5]octan-8-ol Chemical compound C([C@H](C1(CC1)CC1)O)N1CC1=CC=CC=C1 JWSLQKOQLDDQHH-CYBMUJFWSA-N 0.000 description 2
- FFKGOJWPSXRALK-SNAWJCMRSA-N (e)-3-(3-chlorophenyl)prop-2-enoic acid Chemical compound OC(=O)\C=C\C1=CC=CC(Cl)=C1 FFKGOJWPSXRALK-SNAWJCMRSA-N 0.000 description 2
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
- GTYHQWCAHHGHRG-FNORWQNLSA-N 1-[(e)-3-(3,4-dichlorophenyl)prop-2-enoyl]-4-(1-hydroxy-4-oxo-4-piperidin-1-ylbutan-2-yl)-1,4-diazepan-5-one Chemical compound C1CN(C(=O)\C=C\C=2C=C(Cl)C(Cl)=CC=2)CCC(=O)N1C(CO)CC(=O)N1CCCCC1 GTYHQWCAHHGHRG-FNORWQNLSA-N 0.000 description 2
- FNXRDTPGYGBJPT-SNAWJCMRSA-N 1-[(e)-3-(3-chlorophenyl)prop-2-enoyl]-1,4-diazepan-5-one Chemical compound ClC1=CC=CC(\C=C\C(=O)N2CCC(=O)NCC2)=C1 FNXRDTPGYGBJPT-SNAWJCMRSA-N 0.000 description 2
- FHKRUFMHFFJEEO-UHFFFAOYSA-N 1-benzyl-4-(hydroxymethyl)-4-methylpiperidin-3-ol Chemical compound C1C(O)C(C)(CO)CCN1CC1=CC=CC=C1 FHKRUFMHFFJEEO-UHFFFAOYSA-N 0.000 description 2
- CZOOOJDGIBTEOZ-UHFFFAOYSA-N 1-chloro-4-isocyanato-2-(trifluoromethoxy)benzene Chemical compound FC(F)(F)OC1=CC(N=C=O)=CC=C1Cl CZOOOJDGIBTEOZ-UHFFFAOYSA-N 0.000 description 2
- OKJYBJOTWLVTAO-UHFFFAOYSA-N 1-isocyanato-3-(trifluoromethoxy)benzene Chemical compound FC(F)(F)OC1=CC=CC(N=C=O)=C1 OKJYBJOTWLVTAO-UHFFFAOYSA-N 0.000 description 2
- KVYOWXUQJLOCIA-UHFFFAOYSA-N 1-oxa-8-azaspiro[4.5]decane Chemical compound C1CCOC21CCNCC2 KVYOWXUQJLOCIA-UHFFFAOYSA-N 0.000 description 2
- YCHKQUJFRCYZQT-UHFFFAOYSA-N 1-prop-2-enylcyclopropane-1-carboxylic acid Chemical compound C=CCC1(C(=O)O)CC1 YCHKQUJFRCYZQT-UHFFFAOYSA-N 0.000 description 2
- WMWTXZVGAUOTAB-AWEZNQCLSA-N 2,2-dimethyl-4-[(3s)-3-methyl-2-oxo-4-phenylmethoxycarbonylpiperazin-1-yl]butanoic acid Chemical compound C1CN(CCC(C)(C)C(O)=O)C(=O)[C@H](C)N1C(=O)OCC1=CC=CC=C1 WMWTXZVGAUOTAB-AWEZNQCLSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- MLNYXYIVNGRFMK-UHFFFAOYSA-N 2-[3,4-bis(trifluoromethyl)anilino]propan-1-ol Chemical compound OCC(C)NC1=CC=C(C(F)(F)F)C(C(F)(F)F)=C1 MLNYXYIVNGRFMK-UHFFFAOYSA-N 0.000 description 2
- PWQYLXKGOADTBZ-UHFFFAOYSA-N 2-[3,4-bis(trifluoromethyl)anilino]propanoic acid Chemical compound OC(=O)C(C)NC1=CC=C(C(F)(F)F)C(C(F)(F)F)=C1 PWQYLXKGOADTBZ-UHFFFAOYSA-N 0.000 description 2
- 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 2
- ZXPYJLQLURUSAK-DUXPYHPUSA-N 2-[4-[(e)-3-(3,4-dichlorophenyl)prop-2-enoyl]-7-oxo-1,4-diazepan-1-yl]acetic acid Chemical compound C1CC(=O)N(CC(=O)O)CCN1C(=O)\C=C\C1=CC=C(Cl)C(Cl)=C1 ZXPYJLQLURUSAK-DUXPYHPUSA-N 0.000 description 2
- PYXPVVNETLDIPW-UHFFFAOYSA-N 2-oxa-7-azaspiro[3.5]nonane;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1OCC11CCNCC1 PYXPVVNETLDIPW-UHFFFAOYSA-N 0.000 description 2
- TYMBNRMIBWOQGH-UHFFFAOYSA-N 3,3-dimethoxypropanoic acid Chemical compound COC(OC)CC(O)=O TYMBNRMIBWOQGH-UHFFFAOYSA-N 0.000 description 2
- UVRILKWCQISMRJ-UHFFFAOYSA-N 3-[3-chloro-n-[2-[(4-methoxy-4-oxobutyl)amino]ethyl]-4-(trifluoromethoxy)anilino]propanoic acid;dihydrochloride Chemical compound Cl.Cl.COC(=O)CCCNCCN(CCC(O)=O)C1=CC=C(OC(F)(F)F)C(Cl)=C1 UVRILKWCQISMRJ-UHFFFAOYSA-N 0.000 description 2
- LLDKGUNKYFJNPV-UHFFFAOYSA-N 3-methylpiperidin-3-ol Chemical compound CC1(O)CCCNC1 LLDKGUNKYFJNPV-UHFFFAOYSA-N 0.000 description 2
- YSYNXHZFKGWRAK-SNVBAGLBSA-N 4-[(3r)-4-(3,4-dichlorophenyl)-3-methyl-2-oxopiperazin-1-yl]butanoic acid Chemical compound C1CN(CCCC(O)=O)C(=O)[C@@H](C)N1C1=CC=C(Cl)C(Cl)=C1 YSYNXHZFKGWRAK-SNVBAGLBSA-N 0.000 description 2
- ZZEDJTWGPHLTIM-ZDUSSCGKSA-N 4-[(3s)-3-methyl-2-oxo-4-phenylmethoxycarbonylpiperazin-1-yl]butanoic acid Chemical compound C1CN(CCCC(O)=O)C(=O)[C@H](C)N1C(=O)OCC1=CC=CC=C1 ZZEDJTWGPHLTIM-ZDUSSCGKSA-N 0.000 description 2
- NRMNSFIJDZNDRI-JTQLQIEISA-N 4-[(3s)-4-[3,4-bis(trifluoromethyl)phenyl]-3-methyl-2-oxopiperazin-1-yl]butanoic acid Chemical compound C1CN(CCCC(O)=O)C(=O)[C@H](C)N1C1=CC=C(C(F)(F)F)C(C(F)(F)F)=C1 NRMNSFIJDZNDRI-JTQLQIEISA-N 0.000 description 2
- YWCFRFMMLBLBAY-JTQLQIEISA-N 4-[(3s)-4-[4-chloro-3-(trifluoromethoxy)phenyl]-3-methyl-2-oxopiperazin-1-yl]butanoic acid Chemical compound C1CN(CCCC(O)=O)C(=O)[C@H](C)N1C1=CC=C(Cl)C(OC(F)(F)F)=C1 YWCFRFMMLBLBAY-JTQLQIEISA-N 0.000 description 2
- XEZMUOFWGKRUNW-CYBMUJFWSA-N 4-[4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-4-oxobutyl]-5-oxo-1,4-diazepane-1-carboxylic acid Chemical compound C([C@H]1O)N(C(=O)CCCN2C(CCN(CC2)C(O)=O)=O)CCC11CC1 XEZMUOFWGKRUNW-CYBMUJFWSA-N 0.000 description 2
- AYPIXUJDZLPLDY-UHFFFAOYSA-N 4-[4-[3-chloro-4-(trifluoromethoxy)phenyl]-7-oxo-1,4-diazepan-1-yl]butanoic acid Chemical compound C1CC(=O)N(CCCC(=O)O)CCN1C1=CC=C(OC(F)(F)F)C(Cl)=C1 AYPIXUJDZLPLDY-UHFFFAOYSA-N 0.000 description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
- FJANWAMBKVZTRG-UHFFFAOYSA-N 4-bromo-2-chloro-1-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(Br)C=C1Cl FJANWAMBKVZTRG-UHFFFAOYSA-N 0.000 description 2
- CJAXOFJRWIZALN-UHFFFAOYSA-N 4-fluoropiperidin-3-ol Chemical compound OC1CNCCC1F CJAXOFJRWIZALN-UHFFFAOYSA-N 0.000 description 2
- ZFTRRMLUWJMFOT-UHFFFAOYSA-N 4-isocyanato-1,2-bis(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(N=C=O)C=C1C(F)(F)F ZFTRRMLUWJMFOT-UHFFFAOYSA-N 0.000 description 2
- FZSBIBXMJKRQIJ-AWEZNQCLSA-N 5-[(3s)-3-methyl-2-oxo-4-phenylmethoxycarbonylpiperazin-1-yl]pentanoic acid Chemical compound C1CN(CCCCC(O)=O)C(=O)[C@H](C)N1C(=O)OCC1=CC=CC=C1 FZSBIBXMJKRQIJ-AWEZNQCLSA-N 0.000 description 2
- IOLVTVCBRYUMLY-WMZOPIPTSA-N 5-o-tert-butyl 1-o-methyl (2s)-2-[(3s)-3-methyl-2-oxo-4-phenylmethoxycarbonylpiperazin-1-yl]pentanedioate Chemical compound C[C@H]1C(=O)N([C@@H](CCC(=O)OC(C)(C)C)C(=O)OC)CCN1C(=O)OCC1=CC=CC=C1 IOLVTVCBRYUMLY-WMZOPIPTSA-N 0.000 description 2
- WDBAVSKPRYVIPB-UHFFFAOYSA-N 6-benzyl-6-azaspiro[2.5]octan-8-one;hydrochloride Chemical compound Cl.C1CC2(CC2)C(=O)CN1CC1=CC=CC=C1 WDBAVSKPRYVIPB-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- 102100024167 C-C chemokine receptor type 3 Human genes 0.000 description 2
- 101710149862 C-C chemokine receptor type 3 Proteins 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 239000004367 Lipase Substances 0.000 description 2
- 102000004882 Lipase Human genes 0.000 description 2
- 108090001060 Lipase Proteins 0.000 description 2
- 239000012448 Lithium borohydride Substances 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 2
- 208000018262 Peripheral vascular disease Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 229930182558 Sterol Chemical class 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 238000006859 Swern oxidation reaction Methods 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- OWCNOBSMYIIXHV-HRAATJIYSA-N [(3s)-1-[4-[(3s)-4-[(3,4-dichlorophenyl)carbamoyl]-3-methyl-2-oxopiperazin-1-yl]butanoyl]-4,4-dimethylpiperidin-3-yl] acetate Chemical compound C=1C=C(Cl)C(Cl)=CC=1NC(=O)N([C@H](C1=O)C)CCN1CCCC(=O)N1CCC(C)(C)[C@H](OC(C)=O)C1 OWCNOBSMYIIXHV-HRAATJIYSA-N 0.000 description 2
- IWTYTFSSTWXZFU-QPJJXVBHSA-N [(e)-3-chloroprop-1-enyl]benzene Chemical compound ClC\C=C\C1=CC=CC=C1 IWTYTFSSTWXZFU-QPJJXVBHSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 229960003767 alanine Drugs 0.000 description 2
- ARHWPKZXBHOEEE-UHFFFAOYSA-N alclofenac Chemical compound OC(=O)CC1=CC=C(OCC=C)C(Cl)=C1 ARHWPKZXBHOEEE-UHFFFAOYSA-N 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 206010003246 arthritis Diseases 0.000 description 2
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 description 2
- IBCXGCIRYGIORJ-HNNXBMFYSA-N benzyl (2s)-2-methyl-4-[3-[(2-methylpropan-2-yl)oxy]-3-oxopropyl]-3-oxopiperazine-1-carboxylate Chemical compound C1CN(CCC(=O)OC(C)(C)C)C(=O)[C@H](C)N1C(=O)OCC1=CC=CC=C1 IBCXGCIRYGIORJ-HNNXBMFYSA-N 0.000 description 2
- RJORTKCRCYBQDG-KRWDZBQOSA-N benzyl (2s)-2-methyl-4-[5-[(2-methylpropan-2-yl)oxy]-5-oxopentyl]-3-oxopiperazine-1-carboxylate Chemical compound C1CN(CCCCC(=O)OC(C)(C)C)C(=O)[C@H](C)N1C(=O)OCC1=CC=CC=C1 RJORTKCRCYBQDG-KRWDZBQOSA-N 0.000 description 2
- NYXOUIVPGQGUER-HNNXBMFYSA-N benzyl (2s)-4-(4-methoxy-3,3-dimethyl-4-oxobutyl)-2-methyl-3-oxopiperazine-1-carboxylate Chemical compound C[C@H]1C(=O)N(CCC(C)(C)C(=O)OC)CCN1C(=O)OCC1=CC=CC=C1 NYXOUIVPGQGUER-HNNXBMFYSA-N 0.000 description 2
- CIQGMKCPQPKLNW-CEWLAPEOSA-N benzyl (2s)-4-[(2r)-5-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-1-methoxy-1,5-dioxopentan-2-yl]-2-methyl-3-oxopiperazine-1-carboxylate Chemical compound C([C@H](C(=O)OC)N1C([C@H](C)N(CC1)C(=O)OCC=1C=CC=CC=1)=O)CC(=O)N(C[C@H]1O)CCC21CC2 CIQGMKCPQPKLNW-CEWLAPEOSA-N 0.000 description 2
- YFCFHMVRSMHWDZ-YSIASYRMSA-N benzyl (2s)-4-[(2s)-2-hydroxy-4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-4-oxobutyl]-2-methyl-3-oxopiperazine-1-carboxylate Chemical compound C([C@H](O)CN1CCN([C@H](C1=O)C)C(=O)OCC=1C=CC=CC=1)C(=O)N(C[C@H]1O)CCC21CC2 YFCFHMVRSMHWDZ-YSIASYRMSA-N 0.000 description 2
- FPMYXMKIRYOYMO-ILWGZMRPSA-N benzyl (2s)-4-[(2s)-5-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-1-methoxy-5-oxopentan-2-yl]-2-methyl-3-oxopiperazine-1-carboxylate Chemical compound C([C@@H](COC)N1C([C@H](C)N(CC1)C(=O)OCC=1C=CC=CC=1)=O)CC(=O)N(C[C@H]1O)CCC21CC2 FPMYXMKIRYOYMO-ILWGZMRPSA-N 0.000 description 2
- RLYOEKVAJPNWSG-YSIASYRMSA-N benzyl (2s)-4-[(3s)-3-hydroxy-4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-4-oxobutyl]-2-methyl-3-oxopiperazine-1-carboxylate Chemical compound O=C([C@@H](O)CCN1CCN([C@H](C1=O)C)C(=O)OCC=1C=CC=CC=1)N(C[C@H]1O)CCC21CC2 RLYOEKVAJPNWSG-YSIASYRMSA-N 0.000 description 2
- ARISMMIFFUHUTG-ATNAJCNCSA-N benzyl (2s)-5-cyano-2-methyl-4-[4-[(2-methylpropan-2-yl)oxy]-4-oxobutyl]-3-oxopiperazine-1-carboxylate Chemical compound C1C(C#N)N(CCCC(=O)OC(C)(C)C)C(=O)[C@H](C)N1C(=O)OCC1=CC=CC=C1 ARISMMIFFUHUTG-ATNAJCNCSA-N 0.000 description 2
- QPRRMGVAJQBIAL-UHFFFAOYSA-N benzyl 2-oxo-1,4-diazepane-1-carboxylate Chemical compound C1CCNCC(=O)N1C(=O)OCC1=CC=CC=C1 QPRRMGVAJQBIAL-UHFFFAOYSA-N 0.000 description 2
- GEZRHASBHQDJDW-UHFFFAOYSA-N benzyl 4-(4-hydroxybutyl)-5-oxo-1,4-diazepane-1-carboxylate Chemical compound C1CC(=O)N(CCCCO)CCN1C(=O)OCC1=CC=CC=C1 GEZRHASBHQDJDW-UHFFFAOYSA-N 0.000 description 2
- DWIDUEKYXPIKKL-QFIPXVFZSA-N benzyl 4-[(2s)-1-methoxy-1-oxo-4-phenylmethoxybutan-2-yl]-5-oxo-1,4-diazepane-1-carboxylate Chemical compound C([C@@H](C(=O)OC)N1C(CCN(CC1)C(=O)OCC=1C=CC=CC=1)=O)COCC1=CC=CC=C1 DWIDUEKYXPIKKL-QFIPXVFZSA-N 0.000 description 2
- CJCMHBCUCHESGV-UHFFFAOYSA-N benzyl 4-[4-[tert-butyl(dimethyl)silyl]oxybutyl]-5-oxo-1,4-diazepane-1-carboxylate Chemical compound C1CC(=O)N(CCCCO[Si](C)(C)C(C)(C)C)CCN1C(=O)OCC1=CC=CC=C1 CJCMHBCUCHESGV-UHFFFAOYSA-N 0.000 description 2
- CTOUWUYDDUSBQE-UHFFFAOYSA-N benzyl piperazine-1-carboxylate Chemical compound C1CNCCN1C(=O)OCC1=CC=CC=C1 CTOUWUYDDUSBQE-UHFFFAOYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 239000007844 bleaching agent Substances 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- NNTOJPXOCKCMKR-UHFFFAOYSA-N boron;pyridine Chemical compound [B].C1=CC=NC=C1 NNTOJPXOCKCMKR-UHFFFAOYSA-N 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 229920002678 cellulose Chemical class 0.000 description 2
- 239000001913 cellulose Chemical class 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 2
- BERDEBHAJNAUOM-UHFFFAOYSA-N copper(i) oxide Chemical compound [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 description 2
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical compound ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 125000004188 dichlorophenyl group Chemical group 0.000 description 2
- HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- MEGHWIAOTJPCHQ-UHFFFAOYSA-N ethenyl butanoate Chemical compound CCCC(=O)OC=C MEGHWIAOTJPCHQ-UHFFFAOYSA-N 0.000 description 2
- GPKUZNJXHRKREX-UHFFFAOYSA-N ethyl 1-benzyl-4-methyl-3-oxopiperidine-4-carboxylate Chemical compound C1C(=O)C(C(=O)OCC)(C)CCN1CC1=CC=CC=C1 GPKUZNJXHRKREX-UHFFFAOYSA-N 0.000 description 2
- MJQLAZAYRJXOHT-GQCTYLIASA-N ethyl 2-[4-[(e)-3-(3,4-dichlorophenyl)prop-2-enoyl]-7-oxo-1,4-diazepan-1-yl]acetate Chemical compound C1CC(=O)N(CC(=O)OCC)CCN1C(=O)\C=C\C1=CC=C(Cl)C(Cl)=C1 MJQLAZAYRJXOHT-GQCTYLIASA-N 0.000 description 2
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 2
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 2
- 150000002191 fatty alcohols Chemical class 0.000 description 2
- FATAVLOOLIRUNA-UHFFFAOYSA-N formylmethyl Chemical group [CH2]C=O FATAVLOOLIRUNA-UHFFFAOYSA-N 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 238000004817 gas chromatography Methods 0.000 description 2
- 229960002989 glutamic acid Drugs 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 239000003978 infusion fluid Substances 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 229960004903 invert sugar Drugs 0.000 description 2
- 125000005956 isoquinolyl group Chemical group 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 235000019421 lipase Nutrition 0.000 description 2
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 2
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 230000000873 masking effect Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- IBIKHMZPHNKTHM-RDTXWAMCSA-N merck compound 25 Chemical compound C1C[C@@H](C(O)=O)[C@H](O)CN1C(C1=C(F)C=CC=C11)=NN1C(=O)C1=C(Cl)C=CC=C1C1CC1 IBIKHMZPHNKTHM-RDTXWAMCSA-N 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 2
- PKJDVBFUJALTOM-RYGJVYDSSA-N methyl (2s)-2-[(3s)-4-[[3-chloro-4-(trifluoromethyl)phenyl]carbamoyl]-3-methyl-2-oxopiperazin-1-yl]-5-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-5-oxopentanoate Chemical compound C([C@@H](C(=O)OC)N1C([C@H](C)N(CC1)C(=O)NC=1C=C(Cl)C(=CC=1)C(F)(F)F)=O)CC(=O)N(C[C@H]1O)CCC21CC2 PKJDVBFUJALTOM-RYGJVYDSSA-N 0.000 description 2
- KIVHRJHVVPXTEH-VWLOTQADSA-N methyl (2s)-2-[2-[[3-[(2-methylpropan-2-yl)oxy]-3-oxopropyl]-phenylmethoxycarbonylamino]ethylamino]-4-phenylmethoxybutanoate Chemical compound C([C@@H](C(=O)OC)NCCN(CCC(=O)OC(C)(C)C)C(=O)OCC=1C=CC=CC=1)COCC1=CC=CC=C1 KIVHRJHVVPXTEH-VWLOTQADSA-N 0.000 description 2
- BSQHATBEOFYEHD-VHSXEESVSA-N methyl (2s)-2-amino-5-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-5-oxopentanoate Chemical compound O[C@@H]1CN(C(=O)CC[C@H](N)C(=O)OC)CCC11CC1 BSQHATBEOFYEHD-VHSXEESVSA-N 0.000 description 2
- HXGXFXBXPGNZKO-BYPYZUCNSA-N methyl (2s)-4-amino-2-hydroxybutanoate Chemical compound COC(=O)[C@@H](O)CCN HXGXFXBXPGNZKO-BYPYZUCNSA-N 0.000 description 2
- XBLAOWUTGATSCJ-QWHCGFSZSA-N methyl (2s)-5-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxopentanoate Chemical compound O[C@@H]1CN(C(=O)CC[C@@H](C(=O)OC)NC(=O)OC(C)(C)C)CCC11CC1 XBLAOWUTGATSCJ-QWHCGFSZSA-N 0.000 description 2
- YEPBMJCGJAPSRE-ZETCQYMHSA-N methyl (3s)-4-(2,2-dimethoxyethylamino)-3-hydroxybutanoate Chemical compound COC(OC)CNC[C@@H](O)CC(=O)OC YEPBMJCGJAPSRE-ZETCQYMHSA-N 0.000 description 2
- CVSAQOIVAWYHJR-JQWIXIFHSA-N methyl (3s)-4-[(3s)-4-[3-chloro-4-(trifluoromethyl)phenyl]-3-methyl-2-oxopiperazin-1-yl]-3-hydroxybutanoate Chemical compound C[C@H]1C(=O)N(C[C@@H](O)CC(=O)OC)CCN1C1=CC=C(C(F)(F)F)C(Cl)=C1 CVSAQOIVAWYHJR-JQWIXIFHSA-N 0.000 description 2
- ZMDBSTXKDVIMKD-AAEUAGOBSA-N methyl (3s)-4-[[(2s)-2-[3-chloro-4-(trifluoromethyl)anilino]propanoyl]-(2,2-dimethoxyethyl)amino]-3-hydroxybutanoate Chemical compound COC(=O)C[C@H](O)CN(CC(OC)OC)C(=O)[C@H](C)NC1=CC=C(C(F)(F)F)C(Cl)=C1 ZMDBSTXKDVIMKD-AAEUAGOBSA-N 0.000 description 2
- UPHAIUPWEBUYAF-HWKANZROSA-N methyl 2-[4-[(e)-3-(3,4-dichlorophenyl)prop-2-enoyl]-7-oxo-1,4-diazepan-1-yl]acetate Chemical compound C1CC(=O)N(CC(=O)OC)CCN1C(=O)\C=C\C1=CC=C(Cl)C(Cl)=C1 UPHAIUPWEBUYAF-HWKANZROSA-N 0.000 description 2
- PGUGZIHSMZYYAL-DOJUMQAQSA-N methyl 3-[[(e)-3-(3-chlorophenyl)prop-2-enoyl]-[(2r)-1-[3-hydroxypropyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]propan-2-yl]amino]propanoate Chemical compound OCCCN(C(=O)OC(C)(C)C)C[C@@H](C)N(CCC(=O)OC)C(=O)\C=C\C1=CC=CC(Cl)=C1 PGUGZIHSMZYYAL-DOJUMQAQSA-N 0.000 description 2
- GESJAOSDFKAEJT-UHFFFAOYSA-N methyl 4-[4-[3-chloro-4-(trifluoromethoxy)phenyl]-7-oxo-1,4-diazepan-1-yl]butanoate Chemical compound C1CC(=O)N(CCCC(=O)OC)CCN1C1=CC=C(OC(F)(F)F)C(Cl)=C1 GESJAOSDFKAEJT-UHFFFAOYSA-N 0.000 description 2
- LKSLDRFFRFOCMO-CSKARUKUSA-N methyl 4-[tert-butyl(dimethyl)silyl]oxy-2-[4-[(e)-3-(3,4-dichlorophenyl)prop-2-enoyl]-7-oxo-1,4-diazepan-1-yl]butanoate Chemical compound C1CC(=O)N(C(CCO[Si](C)(C)C(C)(C)C)C(=O)OC)CCN1C(=O)\C=C\C1=CC=C(Cl)C(Cl)=C1 LKSLDRFFRFOCMO-CSKARUKUSA-N 0.000 description 2
- IBCSLFLNIFFAEP-UHFFFAOYSA-N methyl 4-amino-2-fluorobutanoate Chemical compound COC(=O)C(F)CCN IBCSLFLNIFFAEP-UHFFFAOYSA-N 0.000 description 2
- HXGXFXBXPGNZKO-UHFFFAOYSA-N methyl 4-amino-2-hydroxybutanoate Chemical compound COC(=O)C(O)CCN HXGXFXBXPGNZKO-UHFFFAOYSA-N 0.000 description 2
- QUTSKIWJUHDULC-UHFFFAOYSA-N methyl 4-amino-3-hydroxybutanoate Chemical compound COC(=O)CC(O)CN QUTSKIWJUHDULC-UHFFFAOYSA-N 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- ZSQBWJVNWXAGKO-UHFFFAOYSA-N n-butyl-4,6-dimethyl-n-[[4-[2-(2h-tetrazol-5-yl)phenyl]phenyl]methyl]pyrimidin-2-amine Chemical compound N=1C(C)=CC(C)=NC=1N(CCCC)CC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 ZSQBWJVNWXAGKO-UHFFFAOYSA-N 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 2
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 2
- IWELDVXSEVIIGI-UHFFFAOYSA-N piperazin-2-one Chemical compound O=C1CNCCN1 IWELDVXSEVIIGI-UHFFFAOYSA-N 0.000 description 2
- 229920001223 polyethylene glycol Chemical class 0.000 description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 description 2
- 235000011009 potassium phosphates Nutrition 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 2
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 2
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 125000005493 quinolyl group Chemical group 0.000 description 2
- 239000002464 receptor antagonist Substances 0.000 description 2
- 229940044551 receptor antagonist Drugs 0.000 description 2
- 229910052702 rhenium Inorganic materials 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 239000011877 solvent mixture Substances 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 150000003432 sterols Chemical class 0.000 description 2
- 235000003702 sterols Nutrition 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- LFRRBKUJYGSPDK-NSHDSACASA-N tert-butyl (4s)-4-(2,2-dimethoxyethylamino)-5-methoxypentanoate Chemical compound COC(OC)CN[C@H](COC)CCC(=O)OC(C)(C)C LFRRBKUJYGSPDK-NSHDSACASA-N 0.000 description 2
- GWKHMLJIBPNTKN-QMMMGPOBSA-N tert-butyl (4s)-4-amino-5-methoxypentanoate Chemical compound COC[C@@H](N)CCC(=O)OC(C)(C)C GWKHMLJIBPNTKN-QMMMGPOBSA-N 0.000 description 2
- RLNTXINSDOYKAW-AWEZNQCLSA-N tert-butyl (4s)-5-hydroxy-4-(phenylmethoxycarbonylamino)pentanoate Chemical compound CC(C)(C)OC(=O)CC[C@@H](CO)NC(=O)OCC1=CC=CC=C1 RLNTXINSDOYKAW-AWEZNQCLSA-N 0.000 description 2
- OUEVDVULSUUSCG-HNNXBMFYSA-N tert-butyl (4s)-5-methoxy-4-(phenylmethoxycarbonylamino)pentanoate Chemical compound CC(C)(C)OC(=O)CC[C@@H](COC)NC(=O)OCC1=CC=CC=C1 OUEVDVULSUUSCG-HNNXBMFYSA-N 0.000 description 2
- MQOLTEHTFKRZNV-SECBINFHSA-N tert-butyl (8s)-8-hydroxy-6-azaspiro[2.5]octane-6-carboxylate Chemical compound O[C@@H]1CN(C(=O)OC(C)(C)C)CCC11CC1 MQOLTEHTFKRZNV-SECBINFHSA-N 0.000 description 2
- AFKDGIXGELTYSN-UHFFFAOYSA-N tert-butyl 1-(2-oxoethyl)cyclopropane-1-carboxylate Chemical compound CC(C)(C)OC(=O)C1(CC=O)CC1 AFKDGIXGELTYSN-UHFFFAOYSA-N 0.000 description 2
- YOACTMLTIQRCBS-UHFFFAOYSA-N tert-butyl 1-[2-[benzyl-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]ethyl]cyclopropane-1-carboxylate Chemical compound C=1C=CC=CC=1CN(CC(=O)OC(C)(C)C)CCC1(C(=O)OC(C)(C)C)CC1 YOACTMLTIQRCBS-UHFFFAOYSA-N 0.000 description 2
- XSBSYBJQPDDFEW-UHFFFAOYSA-N tert-butyl 3-[2-hydroxyethyl(phenylmethoxycarbonyl)amino]propanoate Chemical compound CC(C)(C)OC(=O)CCN(CCO)C(=O)OCC1=CC=CC=C1 XSBSYBJQPDDFEW-UHFFFAOYSA-N 0.000 description 2
- CQCWBFNVIOOTSI-UHFFFAOYSA-N tert-butyl 3-[2-oxoethyl(phenylmethoxycarbonyl)amino]propanoate Chemical compound CC(C)(C)OC(=O)CCN(CC=O)C(=O)OCC1=CC=CC=C1 CQCWBFNVIOOTSI-UHFFFAOYSA-N 0.000 description 2
- WTCSKXVMBICKLT-UHFFFAOYSA-N tert-butyl 3-[3-chloro-4-(trifluoromethoxy)anilino]propanoate Chemical compound CC(C)(C)OC(=O)CCNC1=CC=C(OC(F)(F)F)C(Cl)=C1 WTCSKXVMBICKLT-UHFFFAOYSA-N 0.000 description 2
- JNKPTDUUCLUPDQ-UHFFFAOYSA-N tert-butyl 3-[3-chloro-n-(2-hydroxyethyl)-4-(trifluoromethoxy)anilino]propanoate Chemical compound CC(C)(C)OC(=O)CCN(CCO)C1=CC=C(OC(F)(F)F)C(Cl)=C1 JNKPTDUUCLUPDQ-UHFFFAOYSA-N 0.000 description 2
- SRVDIGFNMNTAQJ-UHFFFAOYSA-N tert-butyl 3-[3-chloro-n-(2-methoxy-2-oxoethyl)-4-(trifluoromethoxy)anilino]propanoate Chemical compound CC(C)(C)OC(=O)CCN(CC(=O)OC)C1=CC=C(OC(F)(F)F)C(Cl)=C1 SRVDIGFNMNTAQJ-UHFFFAOYSA-N 0.000 description 2
- OZUXLKZXSRMZHG-UHFFFAOYSA-N tert-butyl 3-[3-chloro-n-(2-oxoethyl)-4-(trifluoromethoxy)anilino]propanoate Chemical compound CC(C)(C)OC(=O)CCN(CC=O)C1=CC=C(OC(F)(F)F)C(Cl)=C1 OZUXLKZXSRMZHG-UHFFFAOYSA-N 0.000 description 2
- DKHTXQAPALNRIQ-BQYQJAHWSA-N tert-butyl 3-[4-[(e)-3-(3-chlorophenyl)prop-2-enoyl]-7-oxo-1,4-diazepan-1-yl]-4-hydroxybutanoate Chemical compound C1CC(=O)N(C(CO)CC(=O)OC(C)(C)C)CCN1C(=O)\C=C\C1=CC=CC(Cl)=C1 DKHTXQAPALNRIQ-BQYQJAHWSA-N 0.000 description 2
- JHHSOLPDCFDEEB-CMDGGOBGSA-N tert-butyl 3-[4-[(e)-3-(3-chlorophenyl)prop-2-enoyl]-7-oxo-1,4-diazepan-1-yl]-4-methoxybutanoate Chemical compound C1CC(=O)N(C(CC(=O)OC(C)(C)C)COC)CCN1C(=O)\C=C\C1=CC=CC(Cl)=C1 JHHSOLPDCFDEEB-CMDGGOBGSA-N 0.000 description 2
- KAAJXUGPUKVVBG-JTQLQIEISA-N tert-butyl 4-[(3s)-3-methyl-2-oxopiperazin-1-yl]butanoate Chemical compound C[C@@H]1NCCN(CCCC(=O)OC(C)(C)C)C1=O KAAJXUGPUKVVBG-JTQLQIEISA-N 0.000 description 2
- PWHWWYJZUIEVDI-AWEZNQCLSA-N tert-butyl 4-[(3s)-4-[(3-chlorophenyl)carbamoyl]-3-methyl-2-oxopiperazin-1-yl]butanoate Chemical compound C1CN(CCCC(=O)OC(C)(C)C)C(=O)[C@H](C)N1C(=O)NC1=CC=CC(Cl)=C1 PWHWWYJZUIEVDI-AWEZNQCLSA-N 0.000 description 2
- YHQWFDPGPLXJET-ZDUSSCGKSA-N tert-butyl 4-[(3s)-4-[3,4-bis(trifluoromethyl)phenyl]-3-methyl-2-oxopiperazin-1-yl]butanoate Chemical compound C1CN(CCCC(=O)OC(C)(C)C)C(=O)[C@H](C)N1C1=CC=C(C(F)(F)F)C(C(F)(F)F)=C1 YHQWFDPGPLXJET-ZDUSSCGKSA-N 0.000 description 2
- DUYSIHGRBVSRTK-CQSZACIVSA-N tert-butyl 4-[[(2r)-2-(3,4-dichloroanilino)propanoyl]-(2,2-dimethoxyethyl)amino]butanoate Chemical compound CC(C)(C)OC(=O)CCCN(CC(OC)OC)C(=O)[C@@H](C)NC1=CC=C(Cl)C(Cl)=C1 DUYSIHGRBVSRTK-CQSZACIVSA-N 0.000 description 2
- XHKUWVBDEQPVJE-OAHLLOKOSA-N tert-butyl 4-[[(2r)-2-[3-chloro-4-(trifluoromethyl)anilino]propyl]-(3,3-dimethoxypropanoyl)amino]butanoate Chemical compound CC(C)(C)OC(=O)CCCN(C(=O)CC(OC)OC)C[C@@H](C)NC1=CC=C(C(F)(F)F)C(Cl)=C1 XHKUWVBDEQPVJE-OAHLLOKOSA-N 0.000 description 2
- IRSSPKBFJDHYKL-AWEZNQCLSA-N tert-butyl 4-[[(2s)-2-[4-chloro-3-(trifluoromethoxy)anilino]propanoyl]-(2,2-dimethoxyethyl)amino]butanoate Chemical compound CC(C)(C)OC(=O)CCCN(CC(OC)OC)C(=O)[C@H](C)NC1=CC=C(Cl)C(OC(F)(F)F)=C1 IRSSPKBFJDHYKL-AWEZNQCLSA-N 0.000 description 2
- CZVNLCOJFFYZPG-UHFFFAOYSA-N tert-butyl 4-aminobutanoate;hydrochloride Chemical compound Cl.CC(C)(C)OC(=O)CCCN CZVNLCOJFFYZPG-UHFFFAOYSA-N 0.000 description 2
- FTEAAYMAQFBUJJ-UHFFFAOYSA-N tert-butyl cyclopropanecarboxylate Chemical compound CC(C)(C)OC(=O)C1CC1 FTEAAYMAQFBUJJ-UHFFFAOYSA-N 0.000 description 2
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 2
- IXOVIWRKIYNFEN-LSDHHAIUSA-N tert-butyl-[(3R,4S)-3-[tert-butyl(dimethyl)silyl]oxypiperidin-4-yl]oxy-dimethylsilane Chemical compound C(C)(C)(C)[Si](O[C@@H]1CNCC[C@@H]1O[Si](C)(C)C(C)(C)C)(C)C IXOVIWRKIYNFEN-LSDHHAIUSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 238000009736 wetting Methods 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 description 2
- BJOWRJDUPYOCEU-UHFFFAOYSA-N (2-methylpyrrolidin-2-yl)methanol Chemical compound OCC1(C)CCCN1 BJOWRJDUPYOCEU-UHFFFAOYSA-N 0.000 description 1
- DGPPDXAEOHGQSU-OAQYLSRUSA-N (2R)-2-(7-oxo-4-phenylmethoxycarbonyl-1,4-diazepan-1-yl)-4-phenylmethoxybutanoic acid Chemical compound C([C@H](C(=O)O)N1C(CCN(CC1)C(=O)OCC=1C=CC=CC=1)=O)COCC1=CC=CC=C1 DGPPDXAEOHGQSU-OAQYLSRUSA-N 0.000 description 1
- ITYFKEJXJSUPIC-UCLAIMLFSA-N (2S)-2-[(3S)-4-[[3-chloro-4-(trifluoromethoxy)phenyl]carbamoyl]-3-methyl-2-oxopiperazin-1-yl]-5-[(8S)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-5-oxopentanoic acid Chemical compound C([C@H](N1CCN([C@H](C1=O)C)C(=O)NC=1C=C(Cl)C(OC(F)(F)F)=CC=1)C(O)=O)CC(=O)N(C[C@H]1O)CCC21CC2 ITYFKEJXJSUPIC-UCLAIMLFSA-N 0.000 description 1
- QGVMEYPEEOZKEL-GFOMBABLSA-N (2r)-1-[(e)-3-(3-chlorophenyl)prop-2-enoyl]-2-methyl-4-(3-oxo-3-piperidin-1-ylpropyl)-1,4-diazepan-5-one Chemical compound C([C@H](N(CCC1=O)C(=O)\C=C\C=2C=C(Cl)C=CC=2)C)N1CCC(=O)N1CCCCC1 QGVMEYPEEOZKEL-GFOMBABLSA-N 0.000 description 1
- KWNKCFAKZXQSBZ-DPTMFGANSA-N (2r)-1-[(e)-3-(3-chlorophenyl)prop-2-enoyl]-4-[3-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-3-oxopropyl]-2-methyl-1,4-diazepan-5-one Chemical compound C([C@H](N(CCC1=O)C(=O)\C=C\C=2C=C(Cl)C=CC=2)C)N1CCC(=O)N(C[C@H]1O)CCC21CC2 KWNKCFAKZXQSBZ-DPTMFGANSA-N 0.000 description 1
- VYDVJHSTFYOOOO-OXQOHEQNSA-N (2r)-1-[3-chloro-4-(trifluoromethyl)phenyl]-4-[4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-4-oxobutyl]-2-methyl-1,4-diazepan-5-one Chemical compound C([C@H](N(CCC1=O)C=2C=C(Cl)C(=CC=2)C(F)(F)F)C)N1CCCC(=O)N(C[C@H]1O)CCC21CC2 VYDVJHSTFYOOOO-OXQOHEQNSA-N 0.000 description 1
- XVBLEFOSGYYGSG-OXQOHEQNSA-N (2r)-1-[3-chloro-4-(trifluoromethyl)phenyl]-4-[4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-4-oxobutyl]-2-methyl-2,3-dihydro-1,4-diazepin-5-one Chemical compound C([C@H](N(C=CC1=O)C=2C=C(Cl)C(=CC=2)C(F)(F)F)C)N1CCCC(=O)N(C[C@H]1O)CCC21CC2 XVBLEFOSGYYGSG-OXQOHEQNSA-N 0.000 description 1
- SUWRMAZHFSUJCB-RXMQYKEDSA-N (2r)-2-(3,4-dichloroanilino)propanoic acid Chemical compound OC(=O)[C@@H](C)NC1=CC=C(Cl)C(Cl)=C1 SUWRMAZHFSUJCB-RXMQYKEDSA-N 0.000 description 1
- GPEODOFMOAIVMT-RXMQYKEDSA-N (2r)-2-[3-chloro-4-(trifluoromethyl)anilino]propanoic acid Chemical compound OC(=O)[C@@H](C)NC1=CC=C(C(F)(F)F)C(Cl)=C1 GPEODOFMOAIVMT-RXMQYKEDSA-N 0.000 description 1
- SSDBXRUQNACQAW-DKRLNXSXSA-N (2r)-2-[4-[(e)-3-(3-chlorophenyl)prop-2-enoyl]-7-oxo-1,4-diazepan-1-yl]-4-hydroxy-n,n-dimethylbutanamide Chemical compound C1CC(=O)N([C@H](CCO)C(=O)N(C)C)CCN1C(=O)\C=C\C1=CC=CC(Cl)=C1 SSDBXRUQNACQAW-DKRLNXSXSA-N 0.000 description 1
- OZQNRUFJWVFUMQ-ZCFIWIBFSA-N (2r)-2-[4-chloro-3-(trifluoromethyl)anilino]propan-1-ol Chemical compound OC[C@@H](C)NC1=CC=C(Cl)C(C(F)(F)F)=C1 OZQNRUFJWVFUMQ-ZCFIWIBFSA-N 0.000 description 1
- OBETXYAYXDNJHR-SSDOTTSWSA-M (2r)-2-ethylhexanoate Chemical compound CCCC[C@@H](CC)C([O-])=O OBETXYAYXDNJHR-SSDOTTSWSA-M 0.000 description 1
- NAMUCZZNPZMZBF-JTQLQIEISA-N (2s)-2-[2-oxoethyl(phenylmethoxycarbonyl)amino]propanoic acid Chemical compound OC(=O)[C@H](C)N(CC=O)C(=O)OCC1=CC=CC=C1 NAMUCZZNPZMZBF-JTQLQIEISA-N 0.000 description 1
- QTPSXPIAJFBGLO-JTQLQIEISA-N (2s)-2-amino-4-phenylmethoxybutanoic acid Chemical compound OC(=O)[C@@H](N)CCOCC1=CC=CC=C1 QTPSXPIAJFBGLO-JTQLQIEISA-N 0.000 description 1
- YQIOFYWNMWVLQL-JSGCOSHPSA-N (2s)-2-hydroxy-4-[(3s)-3-methyl-2-oxo-4-phenylmethoxycarbonylpiperazin-1-yl]butanoic acid Chemical compound C1CN(CC[C@H](O)C(O)=O)C(=O)[C@H](C)N1C(=O)OCC1=CC=CC=C1 YQIOFYWNMWVLQL-JSGCOSHPSA-N 0.000 description 1
- INYLCYHFMGWVHO-LBPRGKRZSA-N (2s)-2-methyl-3-oxo-4-[4-oxo-4-(2-oxo-1-oxa-3,8-diazaspiro[4.5]decan-8-yl)butyl]piperazine-1-carboxylic acid Chemical compound O=C1[C@H](C)N(C(O)=O)CCN1CCCC(=O)N1CCC2(OC(=O)NC2)CC1 INYLCYHFMGWVHO-LBPRGKRZSA-N 0.000 description 1
- IFPVCNFCQQFSAJ-NSHDSACASA-N (2s)-2-methyl-3-oxo-4-[4-oxo-4-[4-(trifluoromethyl)piperidin-1-yl]butyl]piperazine-1-carboxylic acid Chemical compound O=C1[C@H](C)N(C(O)=O)CCN1CCCC(=O)N1CCC(C(F)(F)F)CC1 IFPVCNFCQQFSAJ-NSHDSACASA-N 0.000 description 1
- XNKMCHLDDOIACT-AWEZNQCLSA-N (2s)-2-methyl-4-[4-(1-oxa-8-azaspiro[4.5]decan-8-yl)-4-oxobutyl]-3-oxopiperazine-1-carboxylic acid Chemical compound O=C1[C@H](C)N(C(O)=O)CCN1CCCC(=O)N1CCC2(OCCC2)CC1 XNKMCHLDDOIACT-AWEZNQCLSA-N 0.000 description 1
- OCRXLPHXHKXNAY-PXYINDEMSA-N (2s)-4-[4-(3-hydroxypiperidin-1-yl)-4-oxobutyl]-2-methyl-3-oxopiperazine-1-carboxylic acid Chemical compound O=C1[C@H](C)N(C(O)=O)CCN1CCCC(=O)N1CC(O)CCC1 OCRXLPHXHKXNAY-PXYINDEMSA-N 0.000 description 1
- ZHZUVXCYIFEUSC-RWMBFGLXSA-N (2s)-4-[4-[(3s,4s)-3-hydroxy-4-methylpiperidin-1-yl]-4-oxobutyl]-2-methyl-3-oxopiperazine-1-carboxylic acid Chemical compound C1[C@@H](O)[C@@H](C)CCN1C(=O)CCCN1C(=O)[C@H](C)N(C(O)=O)CC1 ZHZUVXCYIFEUSC-RWMBFGLXSA-N 0.000 description 1
- FSMFSKFTZOMZCP-AVGNSLFASA-N (2s)-4-[4-[(3s,5s)-3-hydroxy-5-methylpiperidin-1-yl]-4-oxobutyl]-2-methyl-3-oxopiperazine-1-carboxylic acid Chemical compound C1[C@@H](C)C[C@H](O)CN1C(=O)CCCN1C(=O)[C@H](C)N(C(O)=O)CC1 FSMFSKFTZOMZCP-AVGNSLFASA-N 0.000 description 1
- BJZCUISRASIAAV-QFBILLFUSA-N (2s)-4-[4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-4-oxobutyl]-2-methyl-3-oxo-n-[3-(trifluoromethoxy)phenyl]piperazine-1-carboxamide Chemical compound C=1C=CC(OC(F)(F)F)=CC=1NC(=O)N([C@H](C1=O)C)CCN1CCCC(=O)N(C[C@H]1O)CCC21CC2 BJZCUISRASIAAV-QFBILLFUSA-N 0.000 description 1
- IVUOMFWNDGNLBJ-VKHMYHEASA-N (2s)-4-amino-2-hydroxybutanoic acid Chemical compound NCC[C@H](O)C(O)=O IVUOMFWNDGNLBJ-VKHMYHEASA-N 0.000 description 1
- GLMODRZPPBZPPB-ZDUSSCGKSA-N (2s)-5-[(2-methylpropan-2-yl)oxy]-5-oxo-2-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound CC(C)(C)OC(=O)CC[C@@H](C(O)=O)NC(=O)OCC1=CC=CC=C1 GLMODRZPPBZPPB-ZDUSSCGKSA-N 0.000 description 1
- AKYNZJQFQOZEDI-ZDUSSCGKSA-N (2s)-n-(3,4-dichlorophenyl)-2-methyl-3-oxo-4-[3-oxo-3-[4-(trifluoromethyl)piperidin-1-yl]propyl]piperazine-1-carboxamide Chemical compound C=1C=C(Cl)C(Cl)=CC=1NC(=O)N([C@H](C1=O)C)CCN1CCC(=O)N1CCC(C(F)(F)F)CC1 AKYNZJQFQOZEDI-ZDUSSCGKSA-N 0.000 description 1
- BRDDVIPGSOFHGA-ZDUSSCGKSA-N (2s)-n-(3,4-dichlorophenyl)-2-methyl-4-(3-morpholin-4-yl-3-oxopropyl)-3-oxopiperazine-1-carboxamide Chemical compound C=1C=C(Cl)C(Cl)=CC=1NC(=O)N([C@H](C1=O)C)CCN1CCC(=O)N1CCOCC1 BRDDVIPGSOFHGA-ZDUSSCGKSA-N 0.000 description 1
- CKTNJHAGUHEUEL-CDEQTRAXSA-N (2s)-n-(3,4-dichlorophenyl)-4-[3-(4-fluoro-3-hydroxypiperidin-1-yl)-3-oxopropyl]-2-methyl-3-oxopiperazine-1-carboxamide Chemical compound C=1C=C(Cl)C(Cl)=CC=1NC(=O)N([C@H](C1=O)C)CCN1CCC(=O)N1CCC(F)C(O)C1 CKTNJHAGUHEUEL-CDEQTRAXSA-N 0.000 description 1
- KODJLBPLOHWBFF-SUNYJGFJSA-N (2s)-n-(3,4-dichlorophenyl)-4-[3-[(3s,4s)-3-hydroxy-4-methylpiperidin-1-yl]-3-oxopropyl]-2-methyl-3-oxopiperazine-1-carboxamide Chemical compound C1[C@@H](O)[C@@H](C)CCN1C(=O)CCN1C(=O)[C@H](C)N(C(=O)NC=2C=C(Cl)C(Cl)=CC=2)CC1 KODJLBPLOHWBFF-SUNYJGFJSA-N 0.000 description 1
- FFOWKQMYDCCECT-DZKIICNBSA-N (2s)-n-(3,4-dichlorophenyl)-4-[3-[(3s,5s)-3-hydroxy-5-methylpiperidin-1-yl]-3-oxopropyl]-2-methyl-3-oxopiperazine-1-carboxamide Chemical compound C1[C@@H](C)C[C@H](O)CN1C(=O)CCN1C(=O)[C@H](C)N(C(=O)NC=2C=C(Cl)C(Cl)=CC=2)CC1 FFOWKQMYDCCECT-DZKIICNBSA-N 0.000 description 1
- XZGLNHJNJWCIIJ-KBXCAEBGSA-N (2s)-n-(3,4-dichlorophenyl)-4-[3-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-3-oxopropyl]-2-methyl-3-oxopiperazine-1-carboxamide Chemical compound C=1C=C(Cl)C(Cl)=CC=1NC(=O)N([C@H](C1=O)C)CCN1CCC(=O)N(C[C@H]1O)CCC21CC2 XZGLNHJNJWCIIJ-KBXCAEBGSA-N 0.000 description 1
- QUQPPYYSHDJQAW-HNAYVOBHSA-N (2s)-n-(3,4-dichlorophenyl)-4-[4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-4-oxobutyl]-2-methyl-3-oxopiperazine-1-carboxamide Chemical compound C=1C=C(Cl)C(Cl)=CC=1NC(=O)N([C@H](C1=O)C)CCN1CCCC(=O)N(C[C@H]1O)CCC21CC2 QUQPPYYSHDJQAW-HNAYVOBHSA-N 0.000 description 1
- QVAAAKYQZAVSIY-QFBILLFUSA-N (2s)-n-(4-chlorophenyl)-4-[4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-4-oxobutyl]-2-methyl-3-oxopiperazine-1-carboxamide Chemical compound C=1C=C(Cl)C=CC=1NC(=O)N([C@H](C1=O)C)CCN1CCCC(=O)N(C[C@H]1O)CCC21CC2 QVAAAKYQZAVSIY-QFBILLFUSA-N 0.000 description 1
- HQPGHJDPMYJKDA-ZSZQSSIHSA-N (2s)-n-[3-chloro-4-(trifluoromethoxy)phenyl]-4-[(2r)-2-hydroxy-4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-4-oxobutyl]-2-methyl-3-oxopiperazine-1-carboxamide Chemical compound C([C@@H](O)CN1CCN([C@H](C1=O)C)C(=O)NC=1C=C(Cl)C(OC(F)(F)F)=CC=1)C(=O)N(C[C@H]1O)CCC21CC2 HQPGHJDPMYJKDA-ZSZQSSIHSA-N 0.000 description 1
- HNWVXMQHVCTDKG-DJPFJPOOSA-N (2s)-n-[3-chloro-4-(trifluoromethoxy)phenyl]-4-[(2s)-1-hydroxy-5-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-5-oxopentan-2-yl]-n,2-dimethyl-3-oxopiperazine-1-carboxamide Chemical compound C([C@@H](CO)N1CCN([C@H](C1=O)C)C(=O)N(C)C=1C=C(Cl)C(OC(F)(F)F)=CC=1)CC(=O)N(C[C@H]1O)CCC21CC2 HNWVXMQHVCTDKG-DJPFJPOOSA-N 0.000 description 1
- ZLKYQALTINYNSK-HNAYVOBHSA-N (2s)-n-[3-chloro-4-(trifluoromethoxy)phenyl]-4-[4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-4-oxobutyl]-2-methyl-3-oxopiperazine-1-carboxamide Chemical compound C=1C=C(OC(F)(F)F)C(Cl)=CC=1NC(=O)N([C@H](C1=O)C)CCN1CCCC(=O)N(C[C@H]1O)CCC21CC2 ZLKYQALTINYNSK-HNAYVOBHSA-N 0.000 description 1
- RBMFUSZZXTXMTD-URLQWDBASA-N (2s)-n-[3-chloro-4-(trifluoromethyl)phenyl]-4-[(2s)-2-hydroxy-4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-4-oxobutyl]-2-methyl-3-oxopiperazine-1-carboxamide Chemical compound C([C@H](O)CN1CCN([C@H](C1=O)C)C(=O)NC=1C=C(Cl)C(=CC=1)C(F)(F)F)C(=O)N(C[C@H]1O)CCC21CC2 RBMFUSZZXTXMTD-URLQWDBASA-N 0.000 description 1
- IVPJXZZIMUKBRE-OXJNMPFZSA-N (2s)-n-[3-chloro-4-(trifluoromethyl)phenyl]-4-[4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-3,3-dimethyl-4-oxobutyl]-2-methyl-3-oxopiperazine-1-carboxamide Chemical compound C=1C=C(C(F)(F)F)C(Cl)=CC=1NC(=O)N([C@H](C1=O)C)CCN1CCC(C)(C)C(=O)N(C[C@H]1O)CCC21CC2 IVPJXZZIMUKBRE-OXJNMPFZSA-N 0.000 description 1
- GPCXCDPQYFZHKF-HNAYVOBHSA-N (2s)-n-[4-chloro-3-(trifluoromethoxy)phenyl]-4-[4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-4-oxobutyl]-2-methyl-3-oxopiperazine-1-carboxamide Chemical compound C=1C=C(Cl)C(OC(F)(F)F)=CC=1NC(=O)N([C@H](C1=O)C)CCN1CCCC(=O)N(C[C@H]1O)CCC21CC2 GPCXCDPQYFZHKF-HNAYVOBHSA-N 0.000 description 1
- NMLBFKOEIKDFCD-HNAYVOBHSA-N (2s)-n-[4-chloro-3-(trifluoromethyl)phenyl]-4-[4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-4-oxobutyl]-2-methyl-3-oxopiperazine-1-carboxamide Chemical compound C=1C=C(Cl)C(C(F)(F)F)=CC=1NC(=O)N([C@H](C1=O)C)CCN1CCCC(=O)N(C[C@H]1O)CCC21CC2 NMLBFKOEIKDFCD-HNAYVOBHSA-N 0.000 description 1
- QRKGXSVBKCBYAF-LBPRGKRZSA-N (3S)-3-[benzyl-(2-ethoxy-2-oxoethyl)amino]butanoic acid Chemical compound C(C1=CC=CC=C1)N([C@H](CC(=O)O)C)CC(=O)OCC QRKGXSVBKCBYAF-LBPRGKRZSA-N 0.000 description 1
- MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 description 1
- ITCAHROGZCCSSJ-FUEXJSSKSA-N (3s)-4-[(e)-3-(3-chloro-4-fluorophenyl)prop-2-enoyl]-1-(3-hydroxypropyl)-3-methylpiperazin-2-one Chemical compound C1CN(CCCO)C(=O)[C@H](C)N1C(=O)\C=C\C1=CC=C(F)C(Cl)=C1 ITCAHROGZCCSSJ-FUEXJSSKSA-N 0.000 description 1
- YQGDEPYYFWUPGO-VKHMYHEASA-N (3s)-4-azaniumyl-3-hydroxybutanoate Chemical compound [NH3+]C[C@@H](O)CC([O-])=O YQGDEPYYFWUPGO-VKHMYHEASA-N 0.000 description 1
- ADFBVTAJGJLTTL-AAEUAGOBSA-N (3s,5s)-1-benzyl-5-methylpiperidin-3-ol Chemical compound C1[C@@H](C)C[C@H](O)CN1CC1=CC=CC=C1 ADFBVTAJGJLTTL-AAEUAGOBSA-N 0.000 description 1
- GHBJQVDNNNHJFF-YFKPBYRVSA-N (4S)-4-amino-5-methoxypentanoic acid Chemical compound COC[C@@H](N)CCC(O)=O GHBJQVDNNNHJFF-YFKPBYRVSA-N 0.000 description 1
- ALZLTHLQMAFAPA-BYPYZUCNSA-N (4s)-4-methyloxolan-2-one Chemical compound C[C@@H]1COC(=O)C1 ALZLTHLQMAFAPA-BYPYZUCNSA-N 0.000 description 1
- ZAYAFKXUQMTLPL-ZETCQYMHSA-N (4s)-5-methoxy-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxopentanoic acid Chemical compound OC(=O)CC[C@@H](C(=O)OC)NC(=O)OC(C)(C)C ZAYAFKXUQMTLPL-ZETCQYMHSA-N 0.000 description 1
- RRLUFPHCTSFKNR-DUXPYHPUSA-N (e)-3-(3,4-dichlorophenyl)prop-2-enoic acid Chemical compound OC(=O)\C=C\C1=CC=C(Cl)C(Cl)=C1 RRLUFPHCTSFKNR-DUXPYHPUSA-N 0.000 description 1
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 description 1
- VHDRSZOHKKZOQF-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoro-2-{4-[(2,2,2-trifluoroethyl)amino]phenyl}propan-2-ol Chemical compound FC(F)(F)C(C(F)(F)F)(O)C1=CC=C(NCC(F)(F)F)C=C1 VHDRSZOHKKZOQF-UHFFFAOYSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- NADPFZNWCQIJJW-UHFFFAOYSA-N 1,2-dichloro-4-iodobenzene Chemical compound ClC1=CC=C(I)C=C1Cl NADPFZNWCQIJJW-UHFFFAOYSA-N 0.000 description 1
- YRIZYWQGELRKNT-UHFFFAOYSA-N 1,3,5-trichloro-1,3,5-triazinane-2,4,6-trione Chemical compound ClN1C(=O)N(Cl)C(=O)N(Cl)C1=O YRIZYWQGELRKNT-UHFFFAOYSA-N 0.000 description 1
- QMWYDZLBWGJQOY-UHFFFAOYSA-N 1,3,8-triazaspiro[4.5]decane Chemical compound N1CNCC11CCNCC1 QMWYDZLBWGJQOY-UHFFFAOYSA-N 0.000 description 1
- OSDNICVILLWNTL-GEMLJDPKSA-N 1,4-diazepan-5-one (3S,5S)-5-methylpiperidin-3-ol Chemical compound C[C@H]1C[C@@H](CNC1)O.N1CCNC(CC1)=O OSDNICVILLWNTL-GEMLJDPKSA-N 0.000 description 1
- FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 1
- WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 1
- XHAWIAYIXUDFBW-HWKANZROSA-N 1-[(e)-3-(3,4-dichlorophenyl)prop-2-enoyl]-4-[3-(1-oxa-8-azaspiro[4.5]decan-8-yl)-3-oxopropyl]-1,4-diazepan-5-one Chemical compound C1=C(Cl)C(Cl)=CC=C1\C=C\C(=O)N1CCC(=O)N(CCC(=O)N2CCC3(OCCC3)CC2)CC1 XHAWIAYIXUDFBW-HWKANZROSA-N 0.000 description 1
- BLFVIBMYRVWNFS-DUXPYHPUSA-N 1-[(e)-3-(3,4-dichlorophenyl)prop-2-enoyl]-4-[3-(3,4-dihydroxypiperidin-1-yl)-3-oxopropyl]-1,4-diazepan-5-one Chemical compound C1C(O)C(O)CCN1C(=O)CCN1C(=O)CCN(C(=O)\C=C\C=2C=C(Cl)C(Cl)=CC=2)CC1 BLFVIBMYRVWNFS-DUXPYHPUSA-N 0.000 description 1
- IKQIOUIOWCFSQP-GQCTYLIASA-N 1-[(e)-3-(3,4-dichlorophenyl)prop-2-enoyl]-4-[3-(3-hydroxy-3-methylpiperidin-1-yl)-3-oxopropyl]-1,4-diazepan-5-one Chemical compound C1C(C)(O)CCCN1C(=O)CCN1C(=O)CCN(C(=O)\C=C\C=2C=C(Cl)C(Cl)=CC=2)CC1 IKQIOUIOWCFSQP-GQCTYLIASA-N 0.000 description 1
- RXAAAFWZDAHOIJ-GQCTYLIASA-N 1-[(e)-3-(3,4-dichlorophenyl)prop-2-enoyl]-4-[3-(3-hydroxypiperidin-1-yl)-3-oxopropyl]-1,4-diazepan-5-one Chemical compound C1C(O)CCCN1C(=O)CCN1C(=O)CCN(C(=O)\C=C\C=2C=C(Cl)C(Cl)=CC=2)CC1 RXAAAFWZDAHOIJ-GQCTYLIASA-N 0.000 description 1
- FNIPFYHYELUMTH-VQHVLOKHSA-N 1-[(e)-3-(3,4-dichlorophenyl)prop-2-enoyl]-4-[3-(4-hydroxy-4-phenylpiperidin-1-yl)-3-oxopropyl]-1,4-diazepan-5-one Chemical compound C1CC(O)(C=2C=CC=CC=2)CCN1C(=O)CCN(C(CC1)=O)CCN1C(=O)\C=C\C1=CC=C(Cl)C(Cl)=C1 FNIPFYHYELUMTH-VQHVLOKHSA-N 0.000 description 1
- ILRGKISCXLETBN-HWKANZROSA-N 1-[(e)-3-(3,4-dichlorophenyl)prop-2-enoyl]-4-[3-(4-methyl-3-oxopiperazin-1-yl)-3-oxopropyl]-1,4-diazepan-5-one Chemical compound C1C(=O)N(C)CCN1C(=O)CCN1C(=O)CCN(C(=O)\C=C\C=2C=C(Cl)C(Cl)=CC=2)CC1 ILRGKISCXLETBN-HWKANZROSA-N 0.000 description 1
- HWLOTZKBNOTBCL-HWKANZROSA-N 1-[(e)-3-(3,4-dichlorophenyl)prop-2-enoyl]-4-[3-(4-methylpiperidin-1-yl)-3-oxopropyl]-1,4-diazepan-5-one Chemical compound C1CC(C)CCN1C(=O)CCN1C(=O)CCN(C(=O)\C=C\C=2C=C(Cl)C(Cl)=CC=2)CC1 HWLOTZKBNOTBCL-HWKANZROSA-N 0.000 description 1
- LHCMHIHLYWDZPE-GQCTYLIASA-N 1-[(e)-3-(3,4-dichlorophenyl)prop-2-enoyl]-4-[3-[2-(hydroxymethyl)-2-methylpyrrolidin-1-yl]-3-oxopropyl]-1,4-diazepan-5-one Chemical compound OCC1(C)CCCN1C(=O)CCN1C(=O)CCN(C(=O)\C=C\C=2C=C(Cl)C(Cl)=CC=2)CC1 LHCMHIHLYWDZPE-GQCTYLIASA-N 0.000 description 1
- SGFQZRPPBUDOQF-FNORWQNLSA-N 1-[(e)-3-(3,4-dichlorophenyl)prop-2-enoyl]-4-[3-[2-(hydroxymethyl)piperidin-1-yl]-3-oxopropyl]-1,4-diazepan-5-one Chemical compound OCC1CCCCN1C(=O)CCN1C(=O)CCN(C(=O)\C=C\C=2C=C(Cl)C(Cl)=CC=2)CC1 SGFQZRPPBUDOQF-FNORWQNLSA-N 0.000 description 1
- NHLDDDUMJMXLLE-GQCTYLIASA-N 1-[(e)-3-(3,4-dichlorophenyl)prop-2-enoyl]-4-[3-[3-(hydroxymethyl)piperidin-1-yl]-3-oxopropyl]-1,4-diazepan-5-one Chemical compound C1C(CO)CCCN1C(=O)CCN1C(=O)CCN(C(=O)\C=C\C=2C=C(Cl)C(Cl)=CC=2)CC1 NHLDDDUMJMXLLE-GQCTYLIASA-N 0.000 description 1
- XLGREHJRODYAHP-GQCTYLIASA-N 1-[(e)-3-(3,4-dichlorophenyl)prop-2-enoyl]-4-[3-oxo-3-(3-oxopiperidin-1-yl)propyl]-1,4-diazepan-5-one Chemical compound C1=C(Cl)C(Cl)=CC=C1\C=C\C(=O)N1CCC(=O)N(CCC(=O)N2CC(=O)CCC2)CC1 XLGREHJRODYAHP-GQCTYLIASA-N 0.000 description 1
- FLVOVLVVYDGKDM-DUXPYHPUSA-N 1-[(e)-3-(3,4-dichlorophenyl)prop-2-enoyl]-4-[3-oxo-3-[4-(2-oxoimidazolidin-1-yl)piperidin-1-yl]propyl]-1,4-diazepan-5-one Chemical compound C1=C(Cl)C(Cl)=CC=C1\C=C\C(=O)N1CCC(=O)N(CCC(=O)N2CCC(CC2)N2C(NCC2)=O)CC1 FLVOVLVVYDGKDM-DUXPYHPUSA-N 0.000 description 1
- DBGSRZSKGVSXRK-UHFFFAOYSA-N 1-[2-[5-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]acetyl]-3,6-dihydro-2H-pyridine-4-carboxylic acid Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NN=C(O1)CC(=O)N1CCC(=CC1)C(=O)O DBGSRZSKGVSXRK-UHFFFAOYSA-N 0.000 description 1
- CQZNOQOMJMYILZ-DUXPYHPUSA-N 1-[3-[4-[(E)-3-(3,4-dichlorophenyl)prop-2-enoyl]-7-oxo-1,4-diazepan-1-yl]propanoyl]piperidine-4-carboxylic acid Chemical compound ClC=1C=C(C=CC=1Cl)/C=C/C(=O)N1CCN(C(CC1)=O)CCC(=O)N1CCC(CC1)C(=O)O CQZNOQOMJMYILZ-DUXPYHPUSA-N 0.000 description 1
- BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 1
- NOHQUGRVHSJYMR-UHFFFAOYSA-N 1-chloro-2-isocyanatobenzene Chemical compound ClC1=CC=CC=C1N=C=O NOHQUGRVHSJYMR-UHFFFAOYSA-N 0.000 description 1
- HHIRBXHEYVDUAM-UHFFFAOYSA-N 1-chloro-3-isocyanatobenzene Chemical compound ClC1=CC=CC(N=C=O)=C1 HHIRBXHEYVDUAM-UHFFFAOYSA-N 0.000 description 1
- MCIFWVOVVPVBRJ-UHFFFAOYSA-N 1-chloro-4-iodo-2-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC(I)=CC=C1Cl MCIFWVOVVPVBRJ-UHFFFAOYSA-N 0.000 description 1
- NBJZEUQTGLSUOB-UHFFFAOYSA-N 1-chloro-4-isocyanato-2-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC(N=C=O)=CC=C1Cl NBJZEUQTGLSUOB-UHFFFAOYSA-N 0.000 description 1
- ADAKRBAJFHTIEW-UHFFFAOYSA-N 1-chloro-4-isocyanatobenzene Chemical compound ClC1=CC=C(N=C=O)C=C1 ADAKRBAJFHTIEW-UHFFFAOYSA-N 0.000 description 1
- 125000004776 1-fluoroethyl group Chemical group [H]C([H])([H])C([H])(F)* 0.000 description 1
- SNUSZUYTMHKCPM-UHFFFAOYSA-N 1-hydroxypyridin-2-one Chemical compound ON1C=CC=CC1=O SNUSZUYTMHKCPM-UHFFFAOYSA-N 0.000 description 1
- GZWGTVZRRFPVAS-UHFFFAOYSA-N 1-isocyanato-2-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1N=C=O GZWGTVZRRFPVAS-UHFFFAOYSA-N 0.000 description 1
- SXJYSIBLFGQAND-UHFFFAOYSA-N 1-isocyanato-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC(N=C=O)=C1 SXJYSIBLFGQAND-UHFFFAOYSA-N 0.000 description 1
- QZTWVDCKDWZCLV-UHFFFAOYSA-N 1-isocyanato-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(N=C=O)C=C1 QZTWVDCKDWZCLV-UHFFFAOYSA-N 0.000 description 1
- SHYOJVDXMSYFCK-DAFXYXGESA-N 1-o-benzyl 3-o-methyl (3s)-6-methyl-4-[4-[(2-methylpropan-2-yl)oxy]-4-oxobutyl]-5-oxopiperazine-1,3-dicarboxylate Chemical compound CC1C(=O)N(CCCC(=O)OC(C)(C)C)[C@H](C(=O)OC)CN1C(=O)OCC1=CC=CC=C1 SHYOJVDXMSYFCK-DAFXYXGESA-N 0.000 description 1
- POIQNNXFZFULGW-UHFFFAOYSA-N 1-oxa-3,8-diazaspiro[4.5]decane Chemical compound O1CNCC11CCNCC1 POIQNNXFZFULGW-UHFFFAOYSA-N 0.000 description 1
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- VUZNLSBZRVZGIK-UHFFFAOYSA-N 2,2,6,6-Tetramethyl-1-piperidinol Chemical group CC1(C)CCCC(C)(C)N1O VUZNLSBZRVZGIK-UHFFFAOYSA-N 0.000 description 1
- JDEUUKYNTHHAQH-UHFFFAOYSA-N 2,2-dimethylbutanamide Chemical compound CCC(C)(C)C(N)=O JDEUUKYNTHHAQH-UHFFFAOYSA-N 0.000 description 1
- RWMBKMMQEMUWEO-UHFFFAOYSA-N 2,4-dihydro-1h-pyrazin-3-one Chemical compound O=C1CNC=CN1 RWMBKMMQEMUWEO-UHFFFAOYSA-N 0.000 description 1
- FQMZXMVHHKXGTM-UHFFFAOYSA-N 2-(1-adamantyl)-n-[2-[2-(2-hydroxyethylamino)ethylamino]quinolin-5-yl]acetamide Chemical compound C1C(C2)CC(C3)CC2CC13CC(=O)NC1=CC=CC2=NC(NCCNCCO)=CC=C21 FQMZXMVHHKXGTM-UHFFFAOYSA-N 0.000 description 1
- SUWRMAZHFSUJCB-UHFFFAOYSA-N 2-(3,4-dichloroanilino)propanoic acid Chemical compound OC(=O)C(C)NC1=CC=C(Cl)C(Cl)=C1 SUWRMAZHFSUJCB-UHFFFAOYSA-N 0.000 description 1
- SERARPRVBWDEBA-UHFFFAOYSA-N 2-[(phenylhydrazinylidene)methyl]phenol Chemical compound OC1=CC=CC=C1C=NNC1=CC=CC=C1 SERARPRVBWDEBA-UHFFFAOYSA-N 0.000 description 1
- PECYDCOPEXRPAX-GQCTYLIASA-N 2-[4-[(e)-3-(3,4-dichlorophenyl)prop-2-enoyl]-7-oxo-1,4-diazepan-1-yl]-4-hydroxy-n,n-dimethylbutanamide Chemical compound C1CC(=O)N(C(CCO)C(=O)N(C)C)CCN1C(=O)\C=C\C1=CC=C(Cl)C(Cl)=C1 PECYDCOPEXRPAX-GQCTYLIASA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- FBPINGSGHKXIQA-UHFFFAOYSA-N 2-amino-3-(2-carboxyethylsulfanyl)propanoic acid Chemical compound OC(=O)C(N)CSCCC(O)=O FBPINGSGHKXIQA-UHFFFAOYSA-N 0.000 description 1
- ABFPKTQEQNICFT-UHFFFAOYSA-M 2-chloro-1-methylpyridin-1-ium;iodide Chemical compound [I-].C[N+]1=CC=CC=C1Cl ABFPKTQEQNICFT-UHFFFAOYSA-M 0.000 description 1
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- DBRLJBXYPHFHLD-UHFFFAOYSA-N 2-methyl-1,4-diazepan-5-one Chemical compound CC1CNC(=O)CCN1 DBRLJBXYPHFHLD-UHFFFAOYSA-N 0.000 description 1
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
- SLAMLWHELXOEJZ-UHFFFAOYSA-N 2-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1[N+]([O-])=O SLAMLWHELXOEJZ-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
- SCNRDAIXZJFMEX-UHFFFAOYSA-N 3-(3-chlorophenyl)prop-2-enoyl chloride Chemical compound ClC(=O)C=CC1=CC=CC(Cl)=C1 SCNRDAIXZJFMEX-UHFFFAOYSA-N 0.000 description 1
- SADHVOSOZBAAGL-UHFFFAOYSA-N 3-(trifluoromethoxy)aniline Chemical compound NC1=CC=CC(OC(F)(F)F)=C1 SADHVOSOZBAAGL-UHFFFAOYSA-N 0.000 description 1
- NYJUTRYAFPLNGC-FUEXJSSKSA-N 3-[(3s)-4-[(e)-3-(3-chloro-4-fluorophenyl)prop-2-enoyl]-3-methyl-2-oxopiperazin-1-yl]propanal Chemical compound C1CN(CCC=O)C(=O)[C@H](C)N1C(=O)\C=C\C1=CC=C(F)C(Cl)=C1 NYJUTRYAFPLNGC-FUEXJSSKSA-N 0.000 description 1
- RCGNCOQZSBWPRE-TZNOJPMFSA-N 3-[(3s)-4-[(e)-3-(3-chloro-4-fluorophenyl)prop-2-enoyl]-3-methyl-2-oxopiperazin-1-yl]propanoic acid Chemical compound C1CN(CCC(O)=O)C(=O)[C@H](C)N1C(=O)\C=C\C1=CC=C(F)C(Cl)=C1 RCGNCOQZSBWPRE-TZNOJPMFSA-N 0.000 description 1
- WAMDWPPCARTIIE-QFIPXVFZSA-N 3-[2-[[(2s)-1-methoxy-1-oxo-4-phenylmethoxybutan-2-yl]amino]ethyl-phenylmethoxycarbonylamino]propanoic acid Chemical compound C([C@@H](C(=O)OC)NCCN(CCC(O)=O)C(=O)OCC=1C=CC=CC=1)COCC1=CC=CC=C1 WAMDWPPCARTIIE-QFIPXVFZSA-N 0.000 description 1
- QIAJOEYOHLAFRR-AATRIKPKSA-N 3-[4-[(e)-3-(3-chlorophenyl)prop-2-enoyl]-7-oxo-1,4-diazepan-1-yl]-4-methoxybutanoic acid Chemical compound C1CC(=O)N(C(CC(O)=O)COC)CCN1C(=O)\C=C\C1=CC=CC(Cl)=C1 QIAJOEYOHLAFRR-AATRIKPKSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- MOTGWHLULUGBBO-UHFFFAOYSA-N 3-hydroxy-4-methylidenepiperidine-1-carboxylic acid Chemical compound OC1CN(C(O)=O)CCC1=C MOTGWHLULUGBBO-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- XUJFOSLZQITUOI-UHFFFAOYSA-N 4-(trifluoromethoxy)aniline Chemical compound NC1=CC=C(OC(F)(F)F)C=C1 XUJFOSLZQITUOI-UHFFFAOYSA-N 0.000 description 1
- KMUKXPQVPQUCDB-UHFFFAOYSA-N 4-(trifluoromethyl)piperidine;hydrochloride Chemical compound Cl.FC(F)(F)C1CCNCC1 KMUKXPQVPQUCDB-UHFFFAOYSA-N 0.000 description 1
- XQOGPFSVESOYHA-LLVKDONJSA-N 4-[(3r)-4-[4-chloro-3-(trifluoromethyl)phenyl]-3-methyl-7-oxo-2,3-dihydro-1,4-diazepin-1-yl]butanoic acid Chemical compound C[C@@H]1CN(CCCC(O)=O)C(=O)C=CN1C1=CC=C(Cl)C(C(F)(F)F)=C1 XQOGPFSVESOYHA-LLVKDONJSA-N 0.000 description 1
- NJCOUWIDAMGHAC-JTQLQIEISA-N 4-[(3s)-4-[3-chloro-4-(trifluoromethyl)phenyl]-3-methyl-2-oxopiperazin-1-yl]butanoic acid Chemical compound C1CN(CCCC(O)=O)C(=O)[C@H](C)N1C1=CC=C(C(F)(F)F)C(Cl)=C1 NJCOUWIDAMGHAC-JTQLQIEISA-N 0.000 description 1
- RWTXNOPUZAEDNM-GQCTYLIASA-N 4-[3-(8-azaspiro[4.5]decan-8-yl)-3-oxopropyl]-1-[(e)-3-(3,4-dichlorophenyl)prop-2-enoyl]-1,4-diazepan-5-one Chemical compound C1=C(Cl)C(Cl)=CC=C1\C=C\C(=O)N1CCC(=O)N(CCC(=O)N2CCC3(CCCC3)CC2)CC1 RWTXNOPUZAEDNM-GQCTYLIASA-N 0.000 description 1
- SBEOMMHBZTWQLR-UHFFFAOYSA-N 4-azaniumyl-2,2-dimethylbutanoate Chemical compound OC(=O)C(C)(C)CCN SBEOMMHBZTWQLR-UHFFFAOYSA-N 0.000 description 1
- ASXBTBJGHQPOPY-UHFFFAOYSA-N 4-azaniumyl-2-fluorobutanoate Chemical compound NCCC(F)C(O)=O ASXBTBJGHQPOPY-UHFFFAOYSA-N 0.000 description 1
- IVUOMFWNDGNLBJ-UHFFFAOYSA-N 4-azaniumyl-2-hydroxybutanoate Chemical compound NCCC(O)C(O)=O IVUOMFWNDGNLBJ-UHFFFAOYSA-N 0.000 description 1
- RIYJUHWBFADNIE-UHFFFAOYSA-N 4-bromo-1-chloro-2-(trifluoromethoxy)benzene Chemical compound FC(F)(F)OC1=CC(Br)=CC=C1Cl RIYJUHWBFADNIE-UHFFFAOYSA-N 0.000 description 1
- RWTSQATWCKAOBB-UHFFFAOYSA-N 4-chloro-3-(trifluoromethoxy)aniline Chemical compound NC1=CC=C(Cl)C(OC(F)(F)F)=C1 RWTSQATWCKAOBB-UHFFFAOYSA-N 0.000 description 1
- UZOFELREXGAFOI-UHFFFAOYSA-N 4-methylpiperidine Chemical compound CC1CCNCC1 UZOFELREXGAFOI-UHFFFAOYSA-N 0.000 description 1
- WRXXZWHLNOBEMH-SOFGYWHQSA-N 4-o-tert-butyl 1-o-methyl 2-[4-[(e)-3-(3,4-dichlorophenyl)prop-2-enoyl]-7-oxo-1,4-diazepan-1-yl]butanedioate Chemical compound C1CC(=O)N(C(CC(=O)OC(C)(C)C)C(=O)OC)CCN1C(=O)\C=C\C1=CC=C(Cl)C(Cl)=C1 WRXXZWHLNOBEMH-SOFGYWHQSA-N 0.000 description 1
- KQKFQBTWXOGINC-UHFFFAOYSA-N 4-phenylpiperidin-4-ol Chemical compound C=1C=CC=CC=1C1(O)CCNCC1 KQKFQBTWXOGINC-UHFFFAOYSA-N 0.000 description 1
- ASPDJZINBYYZRU-UHFFFAOYSA-N 5-amino-2-chlorobenzotrifluoride Chemical compound NC1=CC=C(Cl)C(C(F)(F)F)=C1 ASPDJZINBYYZRU-UHFFFAOYSA-N 0.000 description 1
- IOLVTVCBRYUMLY-FUHWJXTLSA-N 5-o-tert-butyl 1-o-methyl (2r)-2-[(3s)-3-methyl-2-oxo-4-phenylmethoxycarbonylpiperazin-1-yl]pentanedioate Chemical compound C[C@H]1C(=O)N([C@H](CCC(=O)OC(C)(C)C)C(=O)OC)CCN1C(=O)OCC1=CC=CC=C1 IOLVTVCBRYUMLY-FUHWJXTLSA-N 0.000 description 1
- NVZWMJWMTWOVNJ-UHFFFAOYSA-N 6-azaspiro[3.4]octane Chemical compound C1CCC21CNCC2 NVZWMJWMTWOVNJ-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- DORGWYZNFGJRJG-DUXPYHPUSA-N 8-[3-[4-[(e)-3-(3,4-dichlorophenyl)prop-2-enoyl]-7-oxo-1,4-diazepan-1-yl]propanoyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione Chemical compound C1=C(Cl)C(Cl)=CC=C1\C=C\C(=O)N1CCC(=O)N(CCC(=O)N2CCC3(CC2)C(NC(=O)N3)=O)CC1 DORGWYZNFGJRJG-DUXPYHPUSA-N 0.000 description 1
- NEMVHIFLGXDWEZ-DUXPYHPUSA-N 8-[3-[4-[(e)-3-(3,4-dichlorophenyl)prop-2-enoyl]-7-oxo-1,4-diazepan-1-yl]propanoyl]-2,8-diazaspiro[4.5]decane-1,3-dione Chemical compound C1=C(Cl)C(Cl)=CC=C1\C=C\C(=O)N1CCC(=O)N(CCC(=O)N2CCC3(C(NC(=O)C3)=O)CC2)CC1 NEMVHIFLGXDWEZ-DUXPYHPUSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- 101150083327 CCR2 gene Proteins 0.000 description 1
- 101150004010 CXCR3 gene Proteins 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 102000000018 Chemokine CCL2 Human genes 0.000 description 1
- 241000766026 Coregonus nasus Species 0.000 description 1
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical class [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- WHUUTDBJXJRKMK-GSVOUGTGSA-N D-glutamic acid Chemical compound OC(=O)[C@H](N)CCC(O)=O WHUUTDBJXJRKMK-GSVOUGTGSA-N 0.000 description 1
- 229930182847 D-glutamic acid Natural products 0.000 description 1
- MHZGKXUYDGKKIU-UHFFFAOYSA-N Decylamine Chemical compound CCCCCCCCCCN MHZGKXUYDGKKIU-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 1
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 1
- 240000001414 Eucalyptus viminalis Species 0.000 description 1
- OUVXYXNWSVIOSJ-UHFFFAOYSA-N Fluo-4 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=C(C=2)C2=C3C=C(F)C(=O)C=C3OC3=CC(O)=C(F)C=C32)N(CC(O)=O)CC(O)=O)=C1 OUVXYXNWSVIOSJ-UHFFFAOYSA-N 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 108010050375 Glucose 1-Dehydrogenase Proteins 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 239000007987 MES buffer Substances 0.000 description 1
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- UUIQMZJEGPQKFD-UHFFFAOYSA-N Methyl butyrate Chemical compound CCCC(=O)OC UUIQMZJEGPQKFD-UHFFFAOYSA-N 0.000 description 1
- RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 description 1
- 238000006751 Mitsunobu reaction Methods 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 1
- NNFSEZIFJYXIQM-UHFFFAOYSA-N N1CCS(CC1)(=O)=O.CN1CC(NCC1)=O Chemical compound N1CCS(CC1)(=O)=O.CN1CC(NCC1)=O NNFSEZIFJYXIQM-UHFFFAOYSA-N 0.000 description 1
- DWZWVSSZOFKGCM-UHFFFAOYSA-N NC1=CC(Cl)=CC=C1.FC(C1CCNCC1)(F)F Chemical compound NC1=CC(Cl)=CC=C1.FC(C1CCNCC1)(F)F DWZWVSSZOFKGCM-UHFFFAOYSA-N 0.000 description 1
- JNVARQDVBDVVPJ-UHFFFAOYSA-N O=C(NC1=CC(C(F)(F)F)=C(C(F)(F)F)C=C1)N(CCN1)CC1=O Chemical compound O=C(NC1=CC(C(F)(F)F)=C(C(F)(F)F)C=C1)N(CCN1)CC1=O JNVARQDVBDVVPJ-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- WUGQZFFCHPXWKQ-UHFFFAOYSA-N Propanolamine Chemical compound NCCCO WUGQZFFCHPXWKQ-UHFFFAOYSA-N 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- 101100463660 Sus scrofa NPG2 gene Proteins 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- QYTDEUPAUMOIOP-UHFFFAOYSA-N TEMPO Chemical group CC1(C)CCCC(C)(C)N1[O] QYTDEUPAUMOIOP-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 229910052770 Uranium Inorganic materials 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 101100082060 Xenopus laevis pou5f1.1 gene Proteins 0.000 description 1
- FHNPEEQMBVHARP-VEELZWTKSA-N [1-[3-[4-[(E)-3-(3,4-dichlorophenyl)prop-2-enoyl]-7-oxo-1,4-diazepan-1-yl]propanoyl]piperidin-4-yl]carbamic acid piperidin-4-ylcarbamic acid Chemical compound N1CCC(CC1)NC(O)=O.ClC=1C=C(C=CC1Cl)/C=C/C(=O)N1CCN(C(CC1)=O)CCC(=O)N1CCC(CC1)NC(O)=O FHNPEEQMBVHARP-VEELZWTKSA-N 0.000 description 1
- ZBIKORITPGTTGI-UHFFFAOYSA-N [acetyloxy(phenyl)-$l^{3}-iodanyl] acetate Chemical compound CC(=O)OI(OC(C)=O)C1=CC=CC=C1 ZBIKORITPGTTGI-UHFFFAOYSA-N 0.000 description 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
- 125000004036 acetal group Chemical group 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 238000006359 acetalization reaction Methods 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- FXXACINHVKSMDR-UHFFFAOYSA-N acetyl bromide Chemical compound CC(Br)=O FXXACINHVKSMDR-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 150000001266 acyl halides Chemical class 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- GZCGUPFRVQAUEE-SLPGGIOYSA-N aldehydo-D-glucose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O GZCGUPFRVQAUEE-SLPGGIOYSA-N 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- OBETXYAYXDNJHR-UHFFFAOYSA-N alpha-ethylcaproic acid Natural products CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000010976 amide bond formation reaction Methods 0.000 description 1
- 238000010640 amide synthesis reaction Methods 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000005219 aminonitrile group Chemical group 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- AXMNGEUJXLXFRY-UHFFFAOYSA-N azaspirodecane Chemical compound C1CCCC21CCNCC2 AXMNGEUJXLXFRY-UHFFFAOYSA-N 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 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
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- MJSHDCCLFGOEIK-UHFFFAOYSA-N benzyl (2,5-dioxopyrrolidin-1-yl) carbonate Chemical compound O=C1CCC(=O)N1OC(=O)OCC1=CC=CC=C1 MJSHDCCLFGOEIK-UHFFFAOYSA-N 0.000 description 1
- WFKKDPFHOVISLE-HKUYNNGSSA-N benzyl (2s)-4-[(2s)-1-methoxy-5-[(2-methylpropan-2-yl)oxy]-5-oxopentan-2-yl]-2-methyl-3-oxopiperazine-1-carboxylate Chemical compound C[C@H]1C(=O)N([C@@H](CCC(=O)OC(C)(C)C)COC)CCN1C(=O)OCC1=CC=CC=C1 WFKKDPFHOVISLE-HKUYNNGSSA-N 0.000 description 1
- CIQGMKCPQPKLNW-SESVDKBCSA-N benzyl (2s)-4-[(2s)-5-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-1-methoxy-1,5-dioxopentan-2-yl]-2-methyl-3-oxopiperazine-1-carboxylate Chemical compound C([C@@H](C(=O)OC)N1C([C@H](C)N(CC1)C(=O)OCC=1C=CC=CC=1)=O)CC(=O)N(C[C@H]1O)CCC21CC2 CIQGMKCPQPKLNW-SESVDKBCSA-N 0.000 description 1
- DNMWWGAKGXXKBK-ZFWWWQNUSA-N benzyl (2s)-4-[(3s)-3-hydroxy-4-methoxy-4-oxobutyl]-2-methyl-3-oxopiperazine-1-carboxylate Chemical compound C[C@H]1C(=O)N(CC[C@H](O)C(=O)OC)CCN1C(=O)OCC1=CC=CC=C1 DNMWWGAKGXXKBK-ZFWWWQNUSA-N 0.000 description 1
- OORXWGSCJSQJIN-PZJWPPBQSA-N benzyl (2s)-4-[4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-3,3-dimethyl-4-oxobutyl]-2-methyl-3-oxopiperazine-1-carboxylate Chemical compound C=1C=CC=CC=1COC(=O)N([C@H](C1=O)C)CCN1CCC(C)(C)C(=O)N(C[C@H]1O)CCC21CC2 OORXWGSCJSQJIN-PZJWPPBQSA-N 0.000 description 1
- OUZODVOYXKQNCN-PZJWPPBQSA-N benzyl (2s)-4-[5-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-5-oxopentyl]-2-methyl-3-oxopiperazine-1-carboxylate Chemical compound C=1C=CC=CC=1COC(=O)N([C@H](C1=O)C)CCN1CCCCC(=O)N(C[C@H]1O)CCC21CC2 OUZODVOYXKQNCN-PZJWPPBQSA-N 0.000 description 1
- RNUMISHXYWFZCE-NWDGAFQWSA-N benzyl (3r,4s)-3,4-dihydroxypiperidine-1-carboxylate Chemical compound C1[C@@H](O)[C@@H](O)CCN1C(=O)OCC1=CC=CC=C1 RNUMISHXYWFZCE-NWDGAFQWSA-N 0.000 description 1
- GVWNWBXIOGVZQD-UHFFFAOYSA-N benzyl 2-(hydroxymethyl)-2-methylpyrrolidine-1-carboxylate Chemical compound OCC1(C)CCCN1C(=O)OCC1=CC=CC=C1 GVWNWBXIOGVZQD-UHFFFAOYSA-N 0.000 description 1
- QGOPZRYPDFSHOY-UHFFFAOYSA-N benzyl 2-methyl-3-oxopiperazine-1-carboxylate Chemical compound C1CNC(=O)C(C)N1C(=O)OCC1=CC=CC=C1 QGOPZRYPDFSHOY-UHFFFAOYSA-N 0.000 description 1
- NQMRIGCEHSYQBV-UHFFFAOYSA-N benzyl 2-oxopiperazine-1-carboxylate Chemical compound C1CNCC(=O)N1C(=O)OCC1=CC=CC=C1 NQMRIGCEHSYQBV-UHFFFAOYSA-N 0.000 description 1
- FPNWBKVOQVGNBM-HSZRJFAPSA-N benzyl 4-[(2r)-1-(dimethylamino)-1-oxo-4-phenylmethoxybutan-2-yl]-5-oxo-1,4-diazepane-1-carboxylate Chemical compound C([C@H](C(=O)N(C)C)N1C(CCN(CC1)C(=O)OCC=1C=CC=CC=1)=O)COCC1=CC=CC=C1 FPNWBKVOQVGNBM-HSZRJFAPSA-N 0.000 description 1
- YSMLFDORTCTOQD-HXUWFJFHSA-N benzyl 4-[4-[(8s)-8-hydroxy-6-azaspiro[2.5]octan-6-yl]-4-oxobutyl]-5-oxo-1,4-diazepane-1-carboxylate Chemical compound C([C@H]1O)N(C(=O)CCCN2C(CCN(CC2)C(=O)OCC=2C=CC=CC=2)=O)CCC11CC1 YSMLFDORTCTOQD-HXUWFJFHSA-N 0.000 description 1
- SDCSGJAVJCCSOZ-UHFFFAOYSA-N benzyl 6-amino-5-oxo-1,4-diazepane-1-carboxylate Chemical compound C1CNC(=O)C(N)CN1C(=O)OCC1=CC=CC=C1 SDCSGJAVJCCSOZ-UHFFFAOYSA-N 0.000 description 1
- 238000005574 benzylation reaction Methods 0.000 description 1
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical group C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
- 239000012455 biphasic mixture Substances 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 230000003491 cAMP production Effects 0.000 description 1
- 230000003185 calcium uptake Effects 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 230000009087 cell motility Effects 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 239000002975 chemoattractant Substances 0.000 description 1
- 239000002604 chemokine receptor CCR2 antagonist Substances 0.000 description 1
- 230000035605 chemotaxis Effects 0.000 description 1
- 238000005356 chiral GC Methods 0.000 description 1
- PJGJQVRXEUVAFT-UHFFFAOYSA-N chloroiodomethane Chemical compound ClCI PJGJQVRXEUVAFT-UHFFFAOYSA-N 0.000 description 1
- 125000000068 chlorophenyl group Chemical group 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- 239000012045 crude solution Substances 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 108010011222 cyclo(Arg-Pro) Proteins 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
- ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 1
- 210000004292 cytoskeleton Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- DIBHLCJAJIKHGB-UHFFFAOYSA-N dec-5-ene Chemical compound [CH2]CCCC=CCCCC DIBHLCJAJIKHGB-UHFFFAOYSA-N 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- QPMLSUSACCOBDK-UHFFFAOYSA-N diazepane Chemical class C1CCNNCC1 QPMLSUSACCOBDK-UHFFFAOYSA-N 0.000 description 1
- HWRRFOQZZNSVNK-UHFFFAOYSA-N diazepane-1-carboxylic acid Chemical compound OC(=O)N1CCCCCN1 HWRRFOQZZNSVNK-UHFFFAOYSA-N 0.000 description 1
- ORPJQSFBLBHKPN-UHFFFAOYSA-N dichloromethane;methylsulfinylmethane Chemical compound ClCCl.CS(C)=O ORPJQSFBLBHKPN-UHFFFAOYSA-N 0.000 description 1
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
- HQWPLXHWEZZGKY-UHFFFAOYSA-N diethylzinc Chemical compound CC[Zn]CC HQWPLXHWEZZGKY-UHFFFAOYSA-N 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 229940052303 ethers for general anesthesia Drugs 0.000 description 1
- LZOCKQDPCACCCD-AWEZNQCLSA-N ethyl (3s)-3-[benzyl-(2-ethoxy-2-oxoethyl)amino]butanoate Chemical compound CCOC(=O)C[C@H](C)N(CC(=O)OCC)CC1=CC=CC=C1 LZOCKQDPCACCCD-AWEZNQCLSA-N 0.000 description 1
- VUAMJAQNWQKOTC-LURJTMIESA-N ethyl (3s)-4-bromo-3-methylbutanoate Chemical compound CCOC(=O)C[C@H](C)CBr VUAMJAQNWQKOTC-LURJTMIESA-N 0.000 description 1
- UQOMEAWPKSISII-UHFFFAOYSA-N ethyl 1-benzyl-3-oxopiperidine-4-carboxylate;hydron;chloride Chemical compound Cl.C1C(=O)C(C(=O)OCC)CCN1CC1=CC=CC=C1 UQOMEAWPKSISII-UHFFFAOYSA-N 0.000 description 1
- ULOLIZHBYWAICY-UHFFFAOYSA-N ethyl 2-(benzylamino)acetate Chemical compound CCOC(=O)CNCC1=CC=CC=C1 ULOLIZHBYWAICY-UHFFFAOYSA-N 0.000 description 1
- DSGHRJRRFDDJBW-UHFFFAOYSA-N ethyl 2-[3,4-bis(trifluoromethyl)anilino]propanoate Chemical compound CCOC(=O)C(C)NC1=CC=C(C(F)(F)F)C(C(F)(F)F)=C1 DSGHRJRRFDDJBW-UHFFFAOYSA-N 0.000 description 1
- IXXVHGVJWFWKGD-GQCTYLIASA-N ethyl 3-[4-[(e)-3-(3,4-dichlorophenyl)prop-2-enoyl]-7-oxo-1,4-diazepan-1-yl]propanoate Chemical compound C1CC(=O)N(CCC(=O)OCC)CCN1C(=O)\C=C\C1=CC=C(Cl)C(Cl)=C1 IXXVHGVJWFWKGD-GQCTYLIASA-N 0.000 description 1
- FQTIYMRSUOADDK-UHFFFAOYSA-N ethyl 3-bromopropanoate Chemical compound CCOC(=O)CCBr FQTIYMRSUOADDK-UHFFFAOYSA-N 0.000 description 1
- DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 1
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- YQGDEPYYFWUPGO-UHFFFAOYSA-N gamma-amino-beta-hydroxybutyric acid Chemical compound [NH3+]CC(O)CC([O-])=O YQGDEPYYFWUPGO-UHFFFAOYSA-N 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 150000002374 hemiaminals Chemical class 0.000 description 1
- 238000005734 heterodimerization reaction Methods 0.000 description 1
- 125000004634 hexahydroazepinyl group Chemical group N1(CCCCCC1)* 0.000 description 1
- UQEAIHBTYFGYIE-UHFFFAOYSA-N hexamethyldisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)C UQEAIHBTYFGYIE-UHFFFAOYSA-N 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 238000010965 in-process control Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- SRJOCJYGOFTFLH-UHFFFAOYSA-N isonipecotic acid Chemical compound OC(=O)C1CCNCC1 SRJOCJYGOFTFLH-UHFFFAOYSA-N 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
- 125000003965 isoxazolidinyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 229960002337 magnesium chloride Drugs 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 229940050906 magnesium chloride hexahydrate Drugs 0.000 description 1
- DHRRIBDTHFBPNG-UHFFFAOYSA-L magnesium dichloride hexahydrate Chemical compound O.O.O.O.O.O.[Mg+2].[Cl-].[Cl-] DHRRIBDTHFBPNG-UHFFFAOYSA-L 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- KUCMREAESZXXLG-LURJTMIESA-N methyl (2s)-2-(2,2-dimethoxyethylamino)propanoate Chemical compound COC(OC)CN[C@@H](C)C(=O)OC KUCMREAESZXXLG-LURJTMIESA-N 0.000 description 1
- GDOHPIJZIXCUNQ-LBPRGKRZSA-N methyl (2s)-2-[2,2-dimethoxyethyl(phenylmethoxycarbonyl)amino]propanoate Chemical compound COC(OC)CN([C@@H](C)C(=O)OC)C(=O)OCC1=CC=CC=C1 GDOHPIJZIXCUNQ-LBPRGKRZSA-N 0.000 description 1
- IYUKFAFDFHZKPI-DFWYDOINSA-N methyl (2s)-2-aminopropanoate;hydrochloride Chemical compound Cl.COC(=O)[C@H](C)N IYUKFAFDFHZKPI-DFWYDOINSA-N 0.000 description 1
- DCLHQXCUVDZBNE-VIFPVBQESA-N methyl (2s)-4-[tert-butyl(dimethyl)silyl]oxy-2-hydroxybutanoate Chemical compound COC(=O)[C@@H](O)CCO[Si](C)(C)C(C)(C)C DCLHQXCUVDZBNE-VIFPVBQESA-N 0.000 description 1
- JAGUPWJWERZGMO-JTQLQIEISA-N methyl (2s)-4-[tert-butyl(dimethyl)silyl]oxy-2-methylsulfonyloxybutanoate Chemical compound COC(=O)[C@@H](OS(C)(=O)=O)CCO[Si](C)(C)C(C)(C)C JAGUPWJWERZGMO-JTQLQIEISA-N 0.000 description 1
- YUVINVMUJABVFM-SOFGYWHQSA-N methyl 2-[4-[(e)-3-(3,4-dichlorophenyl)prop-2-enoyl]-7-oxo-1,4-diazepan-1-yl]-4-oxo-4-piperidin-1-ylbutanoate Chemical compound C1CN(C(=O)\C=C\C=2C=C(Cl)C(Cl)=CC=2)CCC(=O)N1C(C(=O)OC)CC(=O)N1CCCCC1 YUVINVMUJABVFM-SOFGYWHQSA-N 0.000 description 1
- CBZJJYCDJFTIOV-AATRIKPKSA-N methyl 2-[4-[(e)-3-(3-chlorophenyl)prop-2-enoyl]-7-oxo-1,4-diazepan-1-yl]acetate Chemical compound C1CC(=O)N(CC(=O)OC)CCN1C(=O)\C=C\C1=CC=CC(Cl)=C1 CBZJJYCDJFTIOV-AATRIKPKSA-N 0.000 description 1
- DDMCDMDOHABRHD-UHFFFAOYSA-N methyl 2-hydroxybutanoate Chemical compound CCC(O)C(=O)OC DDMCDMDOHABRHD-UHFFFAOYSA-N 0.000 description 1
- SMCVPMKCDDNUCQ-UHFFFAOYSA-N methyl 3,3-dimethoxypropanoate Chemical compound COC(OC)CC(=O)OC SMCVPMKCDDNUCQ-UHFFFAOYSA-N 0.000 description 1
- XPAIKGXAVHSZFO-GFCCVEGCSA-N methyl 4-[(3r)-4-[4-chloro-3-(trifluoromethyl)phenyl]-3-methyl-7-oxo-2,3-dihydro-1,4-diazepin-1-yl]butanoate Chemical compound C1=CC(=O)N(CCCC(=O)OC)C[C@@H](C)N1C1=CC=C(Cl)C(C(F)(F)F)=C1 XPAIKGXAVHSZFO-GFCCVEGCSA-N 0.000 description 1
- WFWREVRIZFMVQS-UHFFFAOYSA-N methyl 4-[2-[3-chloro-n-[3-[(2-methylpropan-2-yl)oxy]-3-oxopropyl]-4-(trifluoromethoxy)anilino]ethylamino]butanoate Chemical compound COC(=O)CCCNCCN(CCC(=O)OC(C)(C)C)C1=CC=C(OC(F)(F)F)C(Cl)=C1 WFWREVRIZFMVQS-UHFFFAOYSA-N 0.000 description 1
- CERTUQYWAOGISD-CYBMUJFWSA-N methyl 4-[[(2r)-2-[4-chloro-3-(trifluoromethyl)anilino]propyl]-(3,3-dimethoxypropanoyl)amino]butanoate Chemical compound COC(=O)CCCN(C(=O)CC(OC)OC)C[C@@H](C)NC1=CC=C(Cl)C(C(F)(F)F)=C1 CERTUQYWAOGISD-CYBMUJFWSA-N 0.000 description 1
- NURGKQMFSBSZAC-SNVBAGLBSA-N methyl 4-[[(2r)-2-[4-chloro-3-(trifluoromethyl)anilino]propyl]amino]butanoate Chemical compound COC(=O)CCCNC[C@@H](C)NC1=CC=C(Cl)C(C(F)(F)F)=C1 NURGKQMFSBSZAC-SNVBAGLBSA-N 0.000 description 1
- ZHDRNNOYKXKTCV-UHFFFAOYSA-N methyl 4-amino-2,2-dimethylbutanoate;hydrochloride Chemical compound Cl.COC(=O)C(C)(C)CCN ZHDRNNOYKXKTCV-UHFFFAOYSA-N 0.000 description 1
- KJSCSZQWNCEXBT-UHFFFAOYSA-N methyl 4-piperidin-1-ylbutanoate Chemical compound COC(=O)CCCN1CCCCC1 KJSCSZQWNCEXBT-UHFFFAOYSA-N 0.000 description 1
- RPDQUAKUPUJHIR-UHFFFAOYSA-N methylsulfinylmethane;(2,2,2-trifluoroacetyl) 2,2,2-trifluoroacetate Chemical compound CS(C)=O.FC(F)(F)C(=O)OC(=O)C(F)(F)F RPDQUAKUPUJHIR-UHFFFAOYSA-N 0.000 description 1
- BDGDWWGTAFXEEW-UHFFFAOYSA-N methylsulfinylmethane;oxalyl dichloride Chemical compound CS(C)=O.ClC(=O)C(Cl)=O BDGDWWGTAFXEEW-UHFFFAOYSA-N 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- VIJUZNJJLALGNJ-UHFFFAOYSA-N n,n-dimethylbutanamide Chemical compound CCCC(=O)N(C)C VIJUZNJJLALGNJ-UHFFFAOYSA-N 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- NXZKKDNKJPWQIA-UHFFFAOYSA-N n-[3-(trifluoromethyl)phenyl]piperazine-1-carboxamide Chemical compound FC(F)(F)C1=CC=CC(NC(=O)N2CCNCC2)=C1 NXZKKDNKJPWQIA-UHFFFAOYSA-N 0.000 description 1
- NCDIZAGZBSCIMC-UHFFFAOYSA-N n-[4-(trifluoromethoxy)phenyl]piperazine-1-carboxamide Chemical compound C1=CC(OC(F)(F)F)=CC=C1NC(=O)N1CCNCC1 NCDIZAGZBSCIMC-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- RFIOZSIHFNEKFF-UHFFFAOYSA-N piperazine-1-carboxylic acid Chemical compound OC(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-N 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- PRAYXGYYVXRDDW-UHFFFAOYSA-N piperidin-2-ylmethanol Chemical compound OCC1CCCCN1 PRAYXGYYVXRDDW-UHFFFAOYSA-N 0.000 description 1
- USISRUCGEISZIB-UHFFFAOYSA-N piperidin-3-one Chemical compound O=C1CCCNC1 USISRUCGEISZIB-UHFFFAOYSA-N 0.000 description 1
- VUNPWIPIOOMCPT-UHFFFAOYSA-N piperidin-3-ylmethanol Chemical compound OCC1CCCNC1 VUNPWIPIOOMCPT-UHFFFAOYSA-N 0.000 description 1
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 1
- XBXHCBLBYQEYTI-UHFFFAOYSA-N piperidin-4-ylmethanol Chemical compound OCC1CCNCC1 XBXHCBLBYQEYTI-UHFFFAOYSA-N 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 235000011118 potassium hydroxide Nutrition 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- DBABZHXKTCFAPX-UHFFFAOYSA-N probenecid Chemical compound CCCN(CCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 DBABZHXKTCFAPX-UHFFFAOYSA-N 0.000 description 1
- 229960003081 probenecid Drugs 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006308 propyl amino group Chemical group 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 229950010131 puromycin Drugs 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000004289 pyrazol-3-yl group Chemical group [H]N1N=C(*)C([H])=C1[H] 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000006476 reductive cyclization reaction Methods 0.000 description 1
- 230000027425 release of sequestered calcium ion into cytosol Effects 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- XOVSRHHCHKUFKM-UHFFFAOYSA-N s-methylthiohydroxylamine Chemical compound CSN XOVSRHHCHKUFKM-UHFFFAOYSA-N 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 238000006884 silylation reaction Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- UKLNMMHNWFDKNT-UHFFFAOYSA-M sodium chlorite Chemical compound [Na+].[O-]Cl=O UKLNMMHNWFDKNT-UHFFFAOYSA-M 0.000 description 1
- 229960002218 sodium chlorite Drugs 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
- DJHRXBYWKVQDJY-UHFFFAOYSA-N spiro[4.5]decan-3-one Chemical compound C1C(=O)CCC21CCCCC2 DJHRXBYWKVQDJY-UHFFFAOYSA-N 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- DHCDFWKWKRSZHF-UHFFFAOYSA-N sulfurothioic S-acid Chemical compound OS(O)(=O)=S DHCDFWKWKRSZHF-UHFFFAOYSA-N 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 229950009390 symclosene Drugs 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- KEWCJNYSJHSUEV-SBSPUUFOSA-N tert-butyl (3S)-3-hydroxy-4-methylidenepiperidine-1-carboxylate tert-butyl 3-hydroxy-4-methylidenepiperidine-1-carboxylate Chemical compound C(C)(C)(C)OC(=O)N1CC(C(CC1)=C)O.C(C)(C)(C)OC(=O)N1C[C@H](C(CC1)=C)O KEWCJNYSJHSUEV-SBSPUUFOSA-N 0.000 description 1
- IMRNHROGUGVTAI-SECBINFHSA-N tert-butyl (3s)-3-hydroxy-4-methylidenepiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=C)[C@H](O)C1 IMRNHROGUGVTAI-SECBINFHSA-N 0.000 description 1
- ZYNJYBWAZQABMM-RDJZCZTQSA-N tert-butyl (4s)-4-[[(2s)-2-[3-chloro-4-(trifluoromethyl)anilino]propanoyl]-(2,2-dimethoxyethyl)amino]-5-methoxypentanoate Chemical compound CC(C)(C)OC(=O)CC[C@@H](COC)N(CC(OC)OC)C(=O)[C@H](C)NC1=CC=C(C(F)(F)F)C(Cl)=C1 ZYNJYBWAZQABMM-RDJZCZTQSA-N 0.000 description 1
- UURAHTSUPDIUNL-UHFFFAOYSA-N tert-butyl 2-(benzylamino)acetate Chemical compound CC(C)(C)OC(=O)CNCC1=CC=CC=C1 UURAHTSUPDIUNL-UHFFFAOYSA-N 0.000 description 1
- DHEYWENGQBGNFF-UHFFFAOYSA-N tert-butyl 2-methylidenepiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCCC1=C DHEYWENGQBGNFF-UHFFFAOYSA-N 0.000 description 1
- YVHPBSHIEPPQDC-UHFFFAOYSA-N tert-butyl 2-oxa-7-azaspiro[3.5]nonane-7-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC11COC1 YVHPBSHIEPPQDC-UHFFFAOYSA-N 0.000 description 1
- MWCNLGCAHVCWHG-LBPRGKRZSA-N tert-butyl 3-[(3s)-4-[(3,4-dichlorophenyl)carbamoyl]-3-methyl-2-oxopiperazin-1-yl]propanoate Chemical compound C1CN(CCC(=O)OC(C)(C)C)C(=O)[C@H](C)N1C(=O)NC1=CC=C(Cl)C(Cl)=C1 MWCNLGCAHVCWHG-LBPRGKRZSA-N 0.000 description 1
- DOMTZTVJNZKUNX-UHFFFAOYSA-N tert-butyl 3-aminopropanoate;hydrochloride Chemical compound Cl.CC(C)(C)OC(=O)CCN DOMTZTVJNZKUNX-UHFFFAOYSA-N 0.000 description 1
- RMWVUWLBLWBQDS-UHFFFAOYSA-N tert-butyl 3-bromopropanoate Chemical compound CC(C)(C)OC(=O)CCBr RMWVUWLBLWBQDS-UHFFFAOYSA-N 0.000 description 1
- YPOJUILEIWHAFP-GFCCVEGCSA-N tert-butyl 4-[[(2r)-2-[3-chloro-4-(trifluoromethyl)anilino]propyl]amino]butanoate Chemical compound CC(C)(C)OC(=O)CCCNC[C@@H](C)NC1=CC=C(C(F)(F)F)C(Cl)=C1 YPOJUILEIWHAFP-GFCCVEGCSA-N 0.000 description 1
- YCXMXCOPZYEWLM-AWEZNQCLSA-N tert-butyl 4-[[(2s)-2-[3-chloro-4-(trifluoromethyl)anilino]propanoyl]-(2,2-dimethoxyethyl)amino]butanoate Chemical compound CC(C)(C)OC(=O)CCCN(CC(OC)OC)C(=O)[C@H](C)NC1=CC=C(C(F)(F)F)C(Cl)=C1 YCXMXCOPZYEWLM-AWEZNQCLSA-N 0.000 description 1
- WHHXXWYJKXPBMM-KKFHFHRHSA-N tert-butyl 4-[[1-cyano-2-[[(2s)-1-methoxy-1-oxopropan-2-yl]-phenylmethoxycarbonylamino]ethyl]amino]butanoate Chemical compound CC(C)(C)OC(=O)CCCNC(C#N)CN([C@@H](C)C(=O)OC)C(=O)OCC1=CC=CC=C1 WHHXXWYJKXPBMM-KKFHFHRHSA-N 0.000 description 1
- XFZZZOMHBHBURH-UHFFFAOYSA-N tert-butyl 4-aminobutanoate Chemical compound CC(C)(C)OC(=O)CCCN XFZZZOMHBHBURH-UHFFFAOYSA-N 0.000 description 1
- PWCIHWNRHXPVBJ-UHFFFAOYSA-N tert-butyl 4-aminopentanoate;hydrochloride Chemical compound Cl.CC(N)CCC(=O)OC(C)(C)C PWCIHWNRHXPVBJ-UHFFFAOYSA-N 0.000 description 1
- LGKGJTCIWJSACK-UHFFFAOYSA-N tert-butyl 6-benzyl-8-hydroxy-6-azaspiro[2.5]oct-7-ene-7-carboxylate Chemical compound C1CN(CC=2C=CC=CC=2)C(C(=O)OC(C)(C)C)=C(O)C21CC2 LGKGJTCIWJSACK-UHFFFAOYSA-N 0.000 description 1
- ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 1
- BBORDBQEASTVGR-UHFFFAOYSA-N tert-butyl spiro[2.5]octane-6-carboxylate Chemical compound C1CC(C(=O)OC(C)(C)C)CCC11CC1 BBORDBQEASTVGR-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005887 tetrahydrobenzofuranyl group Chemical group 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
- OSBSFAARYOCBHB-UHFFFAOYSA-N tetrapropylammonium Chemical compound CCC[N+](CCC)(CCC)CCC OSBSFAARYOCBHB-UHFFFAOYSA-N 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- 125000005500 uronium group Chemical group 0.000 description 1
- 230000008478 viral entry into host cell Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/08—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 not condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Pulmonology (AREA)
- Neurosurgery (AREA)
- Rheumatology (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Hematology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Physical Education & Sports Medicine (AREA)
- Endocrinology (AREA)
- Dermatology (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP09173682 | 2009-10-21 | ||
| EP09173682.7 | 2009-10-21 | ||
| PCT/EP2010/065579 WO2011048032A1 (en) | 2009-10-21 | 2010-10-18 | Diazepam derivatives as modulators of chemokine receptors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2010309920A1 true AU2010309920A1 (en) | 2012-06-07 |
Family
ID=43087104
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2010309920A Abandoned AU2010309920A1 (en) | 2009-10-21 | 2010-10-18 | Diazepam derivatives as modulators of chemokine receptors |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US8445674B2 (OSRAM) |
| EP (1) | EP2491022B1 (OSRAM) |
| JP (1) | JP5654027B2 (OSRAM) |
| KR (1) | KR20120070609A (OSRAM) |
| CN (1) | CN102762541B (OSRAM) |
| AU (1) | AU2010309920A1 (OSRAM) |
| BR (1) | BR112012009661A2 (OSRAM) |
| CA (1) | CA2776914A1 (OSRAM) |
| ES (1) | ES2531986T3 (OSRAM) |
| IL (1) | IL218795A0 (OSRAM) |
| IN (1) | IN2012DN03045A (OSRAM) |
| MX (1) | MX2012004112A (OSRAM) |
| WO (1) | WO2011048032A1 (OSRAM) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2764840T3 (es) | 2015-01-28 | 2020-06-04 | Univ Bordeaux | Uso de plerixafor para tratar y/o prevenir exacerbaciones agudas de la enfermedad pulmonar obstructiva crónica |
| WO2017025849A1 (en) | 2015-08-13 | 2017-02-16 | Pfizer Inc. | Bicyclic-fused heteroaryl or aryl compounds |
| CN105906553B (zh) * | 2016-04-21 | 2019-01-29 | 重庆威尔德·浩瑞医药化工有限公司 | 一种n-苄基-4-甲基哌啶-3-酮盐酸盐的合成方法 |
| CN107216335B (zh) * | 2017-06-29 | 2019-04-30 | 上海药明康德新药开发有限公司 | 一种叔丁基1-(羟甲基)-3-氧杂-9-氮杂螺[5.5]十一烷-9-甲酸基酯制法 |
| KR101938991B1 (ko) | 2017-09-25 | 2019-01-15 | 강원대학교산학협력단 | 당뇨병성 합병증의 예방 또는 치료용 약제학적 조성물 |
| CN111423454B (zh) * | 2020-04-24 | 2021-06-22 | 苏州大学 | 哌嗪类化合物及其在制备趋化因子受体ccr2拮抗剂中的应用 |
| CN113200997B (zh) * | 2021-05-07 | 2023-10-03 | 上海合全医药有限公司 | 2,5-二氧杂-8-氮杂螺[3.5]壬烷及其盐的合成方法 |
| EP4382529A1 (en) | 2022-12-07 | 2024-06-12 | Bayer Consumer Care AG | A process for preparing pure (3s)-pyrrolidin-3-ol and pure (3s)-pyrrolidin-3-ol hydrochloride |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0012240D0 (en) | 2000-05-19 | 2000-07-12 | Merck Sharp & Dohme | Therapeutic agents |
| KR20060061393A (ko) * | 2003-10-24 | 2006-06-07 | 에프. 호프만-라 로슈 아게 | Ccr3 수용체 길항제 |
| BRPI0507985A (pt) * | 2004-02-24 | 2007-05-08 | Schering Aktiengellschaft | derivados de piperazina uréia para o tratamento de endometriose |
| JP2007269629A (ja) * | 2004-06-21 | 2007-10-18 | Astellas Pharma Inc | キナゾリン誘導体 |
| WO2007034282A2 (en) | 2005-09-19 | 2007-03-29 | Pfizer Products Inc. | Diaryl-imidazole compounds condensed with a heterocycle as c3a receptor antagonists |
| US7977336B2 (en) | 2006-12-28 | 2011-07-12 | Banyu Pharmaceutical Co. Ltd | Aminopyrimidine derivatives as PLK1 inhibitors |
| JP2010208945A (ja) * | 2007-06-01 | 2010-09-24 | Mitsubishi Tanabe Pharma Corp | 複素環化合物 |
| EP2220055A2 (en) | 2007-07-19 | 2010-08-25 | F. Hoffmann-La Roche AG | Novel heterocyclyl compounds and their use as chemokine antagonists |
| BRPI0916574A2 (pt) * | 2008-07-28 | 2015-11-10 | Hoffmann La Roche | derivados de diazepano e piperazina moduladores de receptores de quiomiocinas |
| WO2011002067A1 (ja) * | 2009-07-02 | 2011-01-06 | 武田薬品工業株式会社 | 複素環化合物およびその用途 |
-
2010
- 2010-10-11 US US12/901,592 patent/US8445674B2/en not_active Expired - Fee Related
- 2010-10-18 AU AU2010309920A patent/AU2010309920A1/en not_active Abandoned
- 2010-10-18 CA CA2776914A patent/CA2776914A1/en not_active Abandoned
- 2010-10-18 CN CN201080047338.2A patent/CN102762541B/zh not_active Expired - Fee Related
- 2010-10-18 MX MX2012004112A patent/MX2012004112A/es active IP Right Grant
- 2010-10-18 BR BR112012009661A patent/BR112012009661A2/pt not_active IP Right Cessation
- 2010-10-18 IN IN3045DEN2012 patent/IN2012DN03045A/en unknown
- 2010-10-18 EP EP10765643.1A patent/EP2491022B1/en not_active Not-in-force
- 2010-10-18 JP JP2012534641A patent/JP5654027B2/ja not_active Expired - Fee Related
- 2010-10-18 WO PCT/EP2010/065579 patent/WO2011048032A1/en not_active Ceased
- 2010-10-18 KR KR1020127012920A patent/KR20120070609A/ko not_active Abandoned
- 2010-10-18 ES ES10765643.1T patent/ES2531986T3/es active Active
-
2012
- 2012-03-22 IL IL218795A patent/IL218795A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| KR20120070609A (ko) | 2012-06-29 |
| JP2013508328A (ja) | 2013-03-07 |
| WO2011048032A1 (en) | 2011-04-28 |
| JP5654027B2 (ja) | 2015-01-14 |
| EP2491022B1 (en) | 2014-12-31 |
| CN102762541A (zh) | 2012-10-31 |
| BR112012009661A2 (pt) | 2016-05-17 |
| CN102762541B (zh) | 2016-03-16 |
| IL218795A0 (en) | 2012-06-28 |
| IN2012DN03045A (OSRAM) | 2015-07-31 |
| ES2531986T3 (es) | 2015-03-23 |
| EP2491022A1 (en) | 2012-08-29 |
| US8445674B2 (en) | 2013-05-21 |
| MX2012004112A (es) | 2012-05-08 |
| CA2776914A1 (en) | 2011-04-28 |
| US20110092698A1 (en) | 2011-04-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP2491022B1 (en) | Diazepan derivatives as modulators of chemokine receptors | |
| AU2007242883B2 (en) | Diazepan derivatives modulators of chemokine receptors | |
| US8063042B2 (en) | Heterocyclic compounds | |
| EP2307387B1 (en) | Novel heterocyclyl compounds for treatment of cardiovascular disease | |
| US8138175B2 (en) | Heterocyclyl compounds | |
| EP2486042B1 (en) | Bicyclic heterocycles and their use as ccr2 receptor antagonists | |
| WO2012130915A1 (en) | Spiroalkene carboxamide derivatives and their use as chemokine receptor modulators |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK4 | Application lapsed section 142(2)(d) - no continuation fee paid for the application |