BRPI0610240A2 - compostos, composição farmacêutica, uso do composto, método de tratamento de uma doença, e, processo para preparação de um composto - Google Patents
compostos, composição farmacêutica, uso do composto, método de tratamento de uma doença, e, processo para preparação de um composto Download PDFInfo
- Publication number
- BRPI0610240A2 BRPI0610240A2 BRPI0610240-9A BRPI0610240A BRPI0610240A2 BR PI0610240 A2 BRPI0610240 A2 BR PI0610240A2 BR PI0610240 A BRPI0610240 A BR PI0610240A BR PI0610240 A2 BRPI0610240 A2 BR PI0610240A2
- Authority
- BR
- Brazil
- Prior art keywords
- hydroxy
- butyl
- acid
- methyl
- sulfonyl
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 234
- 238000000034 method Methods 0.000 title claims abstract description 103
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 40
- 201000010099 disease Diseases 0.000 title claims abstract description 38
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 15
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 12
- -1 -OH Chemical group 0.000 claims abstract description 223
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 33
- 125000003118 aryl group Chemical group 0.000 claims abstract description 28
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 25
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 17
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 17
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 15
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 14
- 125000001424 substituent group Chemical group 0.000 claims abstract description 13
- 125000002877 alkyl aryl group Chemical group 0.000 claims abstract description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 12
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 5
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 4
- 125000006529 (C3-C6) alkyl group Chemical group 0.000 claims abstract description 4
- 239000002253 acid Substances 0.000 claims description 197
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 123
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 94
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 68
- 239000002904 solvent Substances 0.000 claims description 53
- 238000006243 chemical reaction Methods 0.000 claims description 49
- 208000004296 neuralgia Diseases 0.000 claims description 40
- 125000000217 alkyl group Chemical group 0.000 claims description 39
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 34
- 229910052739 hydrogen Inorganic materials 0.000 claims description 31
- 239000001257 hydrogen Substances 0.000 claims description 30
- 125000005843 halogen group Chemical group 0.000 claims description 29
- 230000002981 neuropathic effect Effects 0.000 claims description 29
- 208000006011 Stroke Diseases 0.000 claims description 28
- 238000011282 treatment Methods 0.000 claims description 26
- 208000021722 neuropathic pain Diseases 0.000 claims description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- 208000011580 syndromic disease Diseases 0.000 claims description 23
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 22
- 208000002193 Pain Diseases 0.000 claims description 21
- 230000036407 pain Effects 0.000 claims description 21
- 239000005711 Benzoic acid Substances 0.000 claims description 20
- 235000010233 benzoic acid Nutrition 0.000 claims description 20
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 20
- 238000010992 reflux Methods 0.000 claims description 20
- 125000004076 pyridyl group Chemical group 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 19
- 206010061218 Inflammation Diseases 0.000 claims description 18
- 230000004054 inflammatory process Effects 0.000 claims description 18
- 239000002585 base Substances 0.000 claims description 17
- 206010003246 arthritis Diseases 0.000 claims description 16
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 16
- 208000007848 Alcoholism Diseases 0.000 claims description 15
- 208000001640 Fibromyalgia Diseases 0.000 claims description 15
- 206010065390 Inflammatory pain Diseases 0.000 claims description 15
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- 208000004550 Postoperative Pain Diseases 0.000 claims description 15
- 208000009205 Tinnitus Diseases 0.000 claims description 15
- 201000007930 alcohol dependence Diseases 0.000 claims description 15
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 15
- 230000006378 damage Effects 0.000 claims description 15
- 206010027599 migraine Diseases 0.000 claims description 15
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- 206010002383 Angina Pectoris Diseases 0.000 claims description 14
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 14
- 206010012667 Diabetic glaucoma Diseases 0.000 claims description 14
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 14
- 201000005569 Gout Diseases 0.000 claims description 14
- 206010019196 Head injury Diseases 0.000 claims description 14
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- 208000013016 Hypoglycemia Diseases 0.000 claims description 14
- 206010038923 Retinopathy Diseases 0.000 claims description 14
- 201000011529 cardiovascular cancer Diseases 0.000 claims description 14
- 206010013663 drug dependence Diseases 0.000 claims description 14
- 201000002545 drug psychosis Diseases 0.000 claims description 14
- 230000002218 hypoglycaemic effect Effects 0.000 claims description 14
- 230000000302 ischemic effect Effects 0.000 claims description 14
- 230000005906 menstruation Effects 0.000 claims description 14
- ZWLPBLYKEWSWPD-UHFFFAOYSA-N o-toluic acid Chemical compound CC1=CC=CC=C1C(O)=O ZWLPBLYKEWSWPD-UHFFFAOYSA-N 0.000 claims description 14
- 208000020016 psychiatric disease Diseases 0.000 claims description 14
- 208000011117 substance-related disease Diseases 0.000 claims description 14
- 206010004663 Biliary colic Diseases 0.000 claims description 13
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 13
- 206010037779 Radiculopathy Diseases 0.000 claims description 13
- 206010038419 Renal colic Diseases 0.000 claims description 13
- 208000030533 eye disease Diseases 0.000 claims description 13
- 125000006239 protecting group Chemical group 0.000 claims description 13
- 206010044652 trigeminal neuralgia Diseases 0.000 claims description 13
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 12
- 208000008035 Back Pain Diseases 0.000 claims description 12
- 208000008930 Low Back Pain Diseases 0.000 claims description 12
- 206010036376 Postherpetic Neuralgia Diseases 0.000 claims description 12
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 12
- 125000001917 2,4-dinitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1*)[N+]([O-])=O)[N+]([O-])=O 0.000 claims description 11
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 11
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 claims description 11
- 239000003153 chemical reaction reagent Substances 0.000 claims description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
- 239000012299 nitrogen atmosphere Substances 0.000 claims description 11
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 125000005599 alkyl carboxylate group Chemical group 0.000 claims description 10
- 229910052794 bromium Inorganic materials 0.000 claims description 10
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- 150000002431 hydrogen Chemical class 0.000 claims description 9
- 125000001736 nosyl group Chemical group S(=O)(=O)(C1=CC=C([N+](=O)[O-])C=C1)* 0.000 claims description 9
- 239000003054 catalyst Substances 0.000 claims description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
- YNXAIBACHXTZSL-UHFFFAOYSA-N 3-tert-butyl-2-hydroxy-5-iodo-6-methylbenzoic acid Chemical compound CC1=C(I)C=C(C(C)(C)C)C(O)=C1C(O)=O YNXAIBACHXTZSL-UHFFFAOYSA-N 0.000 claims description 7
- FQLCGAGYZZHGJO-UHFFFAOYSA-N 3-tert-butyl-5-[(2,3-difluorophenyl)methylsulfanyl]-2-hydroxy-6-methylbenzoic acid Chemical compound C1=C(C(C)(C)C)C(O)=C(C(O)=O)C(C)=C1SCC1=CC=CC(F)=C1F FQLCGAGYZZHGJO-UHFFFAOYSA-N 0.000 claims description 7
- 125000001246 bromo group Chemical group Br* 0.000 claims description 7
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 229910052751 metal Inorganic materials 0.000 claims description 7
- 239000002184 metal Substances 0.000 claims description 7
- 125000001624 naphthyl group Chemical group 0.000 claims description 7
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 7
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 7
- 238000002560 therapeutic procedure Methods 0.000 claims description 7
- 125000000335 thiazolyl group Chemical group 0.000 claims description 7
- 125000001544 thienyl group Chemical group 0.000 claims description 7
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 6
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 6
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 229910052740 iodine Inorganic materials 0.000 claims description 6
- 125000002757 morpholinyl group Chemical group 0.000 claims description 6
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
- QVCYGHZDLQNEBV-UHFFFAOYSA-N 2,6-dihydroxy-3,5-di(propan-2-yl)benzoic acid Chemical compound CC(C)C1=CC(C(C)C)=C(O)C(C(O)=O)=C1O QVCYGHZDLQNEBV-UHFFFAOYSA-N 0.000 claims description 5
- FCCFJFNKHFXPRE-UHFFFAOYSA-N 3,5-ditert-butyl-2-chloro-6-hydroxybenzoic acid Chemical compound CC(C)(C)C1=CC(C(C)(C)C)=C(Cl)C(C(O)=O)=C1O FCCFJFNKHFXPRE-UHFFFAOYSA-N 0.000 claims description 5
- UHHCAOIDYYAISM-UHFFFAOYSA-N 3-tert-butyl-2-hydroxy-6-methyl-5-(2,4,5-trichlorophenyl)sulfonylbenzoic acid Chemical compound CC1=C(C(O)=O)C(O)=C(C(C)(C)C)C=C1S(=O)(=O)C1=CC(Cl)=C(Cl)C=C1Cl UHHCAOIDYYAISM-UHFFFAOYSA-N 0.000 claims description 5
- XZHXDDBHLPUXCF-UHFFFAOYSA-N 3-tert-butyl-2-hydroxy-6-methyl-5-(2-phenylacetyl)benzoic acid Chemical compound C1=C(C(C)(C)C)C(O)=C(C(O)=O)C(C)=C1C(=O)CC1=CC=CC=C1 XZHXDDBHLPUXCF-UHFFFAOYSA-N 0.000 claims description 5
- WORPHFONQSOGGY-UHFFFAOYSA-N 3-tert-butyl-2-hydroxy-6-methyl-5-(pyridin-2-ylmethylsulfonyl)benzoic acid Chemical compound CC1=C(C(O)=O)C(O)=C(C(C)(C)C)C=C1S(=O)(=O)CC1=CC=CC=N1 WORPHFONQSOGGY-UHFFFAOYSA-N 0.000 claims description 5
- USCADIULGBDFBJ-UHFFFAOYSA-N 3-tert-butyl-2-hydroxy-6-methyl-5-[[2-(trifluoromethyl)phenyl]methylsulfanyl]benzoic acid Chemical compound C1=C(C(C)(C)C)C(O)=C(C(O)=O)C(C)=C1SCC1=CC=CC=C1C(F)(F)F USCADIULGBDFBJ-UHFFFAOYSA-N 0.000 claims description 5
- HNJJNKTZBVMTQA-UHFFFAOYSA-N 3-tert-butyl-2-hydroxy-6-methyl-5-quinolin-5-ylbenzoic acid Chemical compound C1=C(C(C)(C)C)C(O)=C(C(O)=O)C(C)=C1C1=CC=CC2=NC=CC=C12 HNJJNKTZBVMTQA-UHFFFAOYSA-N 0.000 claims description 5
- KCBDWQDMQPFHMG-UHFFFAOYSA-N 3-tert-butyl-2-hydroxy-6-methyl-5-quinolin-6-ylbenzoic acid Chemical compound C1=C(C(C)(C)C)C(O)=C(C(O)=O)C(C)=C1C1=CC=C(N=CC=C2)C2=C1 KCBDWQDMQPFHMG-UHFFFAOYSA-N 0.000 claims description 5
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 5
- VQFPLZUXQQILSC-UHFFFAOYSA-N 5-(4-chlorophenyl)sulfonyl-2-hydroxy-3-methylbenzoic acid Chemical compound OC(=O)C1=C(O)C(C)=CC(S(=O)(=O)C=2C=CC(Cl)=CC=2)=C1 VQFPLZUXQQILSC-UHFFFAOYSA-N 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910002092 carbon dioxide Inorganic materials 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- PJPFXTWZRXRDQV-UHFFFAOYSA-N 2-hydroxy-3-methyl-5-(4-methylphenyl)sulfonylbenzoic acid Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C1=CC(C)=C(O)C(C(O)=O)=C1 PJPFXTWZRXRDQV-UHFFFAOYSA-N 0.000 claims description 4
- XQOUIFOFSHOCSZ-UHFFFAOYSA-N 2-hydroxy-3-methyl-5-(4-nitrophenyl)sulfanylbenzoic acid Chemical compound OC(=O)C1=C(O)C(C)=CC(SC=2C=CC(=CC=2)[N+]([O-])=O)=C1 XQOUIFOFSHOCSZ-UHFFFAOYSA-N 0.000 claims description 4
- QWLLEQUJUWJUHG-UHFFFAOYSA-N 3-tert-butyl-2,6-dihydroxybenzoic acid Chemical compound CC(C)(C)C1=CC=C(O)C(C(O)=O)=C1O QWLLEQUJUWJUHG-UHFFFAOYSA-N 0.000 claims description 4
- VJGOLFJCUHYYBA-UHFFFAOYSA-N 3-tert-butyl-2-hydroxy-5-(4-nitrophenyl)sulfonylbenzoic acid Chemical compound OC(=O)C1=C(O)C(C(C)(C)C)=CC(S(=O)(=O)C=2C=CC(=CC=2)[N+]([O-])=O)=C1 VJGOLFJCUHYYBA-UHFFFAOYSA-N 0.000 claims description 4
- TXGPKJYQYLPBNW-UHFFFAOYSA-N 3-tert-butyl-2-hydroxy-6-methyl-5-(2-methylpropylsulfanyl)benzoic acid Chemical compound CC(C)CSC1=CC(C(C)(C)C)=C(O)C(C(O)=O)=C1C TXGPKJYQYLPBNW-UHFFFAOYSA-N 0.000 claims description 4
- IPYFOABVDCNLTG-UHFFFAOYSA-N 3-tert-butyl-2-hydroxy-6-methyl-5-(oxan-2-ylmethylsulfanyl)benzoic acid Chemical compound C1=C(C(C)(C)C)C(O)=C(C(O)=O)C(C)=C1SCC1OCCCC1 IPYFOABVDCNLTG-UHFFFAOYSA-N 0.000 claims description 4
- YTZBJKMUFNXILO-UHFFFAOYSA-N 3-tert-butyl-2-hydroxy-6-methyl-5-naphthalen-1-ylbenzoic acid Chemical compound C1=C(C(C)(C)C)C(O)=C(C(O)=O)C(C)=C1C1=CC=CC2=CC=CC=C12 YTZBJKMUFNXILO-UHFFFAOYSA-N 0.000 claims description 4
- OFFCQLUAICHYFW-UHFFFAOYSA-N 3-tert-butyl-2-hydroxy-6-methyl-5-naphthalen-2-ylbenzoic acid Chemical compound C1=C(C(C)(C)C)C(O)=C(C(O)=O)C(C)=C1C1=CC=C(C=CC=C2)C2=C1 OFFCQLUAICHYFW-UHFFFAOYSA-N 0.000 claims description 4
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- ZAIOVJLQRBXGGE-UHFFFAOYSA-N 3-tert-butyl-2-hydroxy-6-methyl-5-quinolin-8-ylbenzoic acid Chemical compound C1=C(C(C)(C)C)C(O)=C(C(O)=O)C(C)=C1C1=CC=CC2=CC=CN=C12 ZAIOVJLQRBXGGE-UHFFFAOYSA-N 0.000 claims description 4
- ATDMYEGPBCPMPB-UHFFFAOYSA-N 3-tert-butyl-5-(2-chloro-4-fluorophenyl)sulfonyl-2-hydroxy-6-methylbenzoic acid Chemical compound CC1=C(C(O)=O)C(O)=C(C(C)(C)C)C=C1S(=O)(=O)C1=CC=C(F)C=C1Cl ATDMYEGPBCPMPB-UHFFFAOYSA-N 0.000 claims description 4
- VKTXSIRRGYFNKD-UHFFFAOYSA-N 3-tert-butyl-5-[(5-fluoro-1,3-benzothiazol-2-yl)methylsulfanyl]-2-hydroxy-6-methylbenzoic acid Chemical compound C1=C(C(C)(C)C)C(O)=C(C(O)=O)C(C)=C1SCC1=NC2=CC(F)=CC=C2S1 VKTXSIRRGYFNKD-UHFFFAOYSA-N 0.000 claims description 4
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 4
- GEJQDHGOCPUXST-UHFFFAOYSA-N 5-(4-bromophenyl)sulfonyl-2-hydroxy-3-methylbenzoic acid Chemical compound OC(=O)C1=C(O)C(C)=CC(S(=O)(=O)C=2C=CC(Br)=CC=2)=C1 GEJQDHGOCPUXST-UHFFFAOYSA-N 0.000 claims description 4
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- 125000005647 linker group Chemical group 0.000 claims description 4
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 4
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 3
- FFGCMGLMRPWHHO-UHFFFAOYSA-N 3,5-ditert-butyl-2,6-dimethoxybenzoic acid Chemical compound COC1=C(C(O)=O)C(OC)=C(C(C)(C)C)C=C1C(C)(C)C FFGCMGLMRPWHHO-UHFFFAOYSA-N 0.000 claims description 3
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- SDFXCZNFRVTXTI-UHFFFAOYSA-N 3-tert-butyl-5-(2,5-dichlorophenyl)sulfanyl-2-hydroxy-6-methylbenzoic acid Chemical compound C1=C(C(C)(C)C)C(O)=C(C(O)=O)C(C)=C1SC1=CC(Cl)=CC=C1Cl SDFXCZNFRVTXTI-UHFFFAOYSA-N 0.000 claims description 3
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- YEESKJGWJFYOOK-IJHYULJSSA-N leukotriene D4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@H](N)C(=O)NCC(O)=O YEESKJGWJFYOOK-IJHYULJSSA-N 0.000 description 1
- OTZRAYGBFWZKMX-JUDRUQEKSA-N leukotriene E4 Chemical compound CCCCCC=CCC=C\C=C\C=C\[C@@H](SC[C@H](N)C(O)=O)[C@@H](O)CCCC(O)=O OTZRAYGBFWZKMX-JUDRUQEKSA-N 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 238000000622 liquid--liquid extraction Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
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- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 1
- OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 1
- WVWZECQNFWFVFW-UHFFFAOYSA-N methyl 2-methylbenzoate Chemical compound COC(=O)C1=CC=CC=C1C WVWZECQNFWFVFW-UHFFFAOYSA-N 0.000 description 1
- MZOBRYTXZZFSOJ-UHFFFAOYSA-N methyl 3,5-dibromo-2,6-dihydroxybenzoate Chemical compound COC(=O)C1=C(O)C(Br)=CC(Br)=C1O MZOBRYTXZZFSOJ-UHFFFAOYSA-N 0.000 description 1
- KOODOQULOCHXBN-UHFFFAOYSA-N methyl 3-tert-butyl-2,6-dihydroxybenzoate Chemical compound COC(=O)C1=C(O)C=CC(C(C)(C)C)=C1O KOODOQULOCHXBN-UHFFFAOYSA-N 0.000 description 1
- KBFAQNLWEHEPFQ-UHFFFAOYSA-N methyl 3-tert-butyl-2-methoxy-6-methyl-5-(3-propan-2-ylbenzoyl)benzoate Chemical compound CC(C)(C)C1=C(OC)C(C(=O)OC)=C(C)C(C(=O)C=2C=C(C=CC=2)C(C)C)=C1 KBFAQNLWEHEPFQ-UHFFFAOYSA-N 0.000 description 1
- MWOOMSFTLUNGOB-UHFFFAOYSA-N methyl 3-tert-butyl-2-methoxy-6-methyl-5-(4-morpholin-4-ylphenyl)benzoate Chemical compound CC(C)(C)C1=C(OC)C(C(=O)OC)=C(C)C(C=2C=CC(=CC=2)N2CCOCC2)=C1 MWOOMSFTLUNGOB-UHFFFAOYSA-N 0.000 description 1
- ZXOAOCFOMGHMJG-UHFFFAOYSA-N methyl 3-tert-butyl-5-(2,4-dichlorobenzoyl)-2-methoxy-6-methylbenzoate Chemical compound CC(C)(C)C1=C(OC)C(C(=O)OC)=C(C)C(C(=O)C=2C(=CC(Cl)=CC=2)Cl)=C1 ZXOAOCFOMGHMJG-UHFFFAOYSA-N 0.000 description 1
- QVZLKSYUYZTETK-UHFFFAOYSA-N methyl 3-tert-butyl-5-(2,4-dichlorophenyl)-2-methoxy-6-methylbenzoate Chemical compound CC(C)(C)C1=C(OC)C(C(=O)OC)=C(C)C(C=2C(=CC(Cl)=CC=2)Cl)=C1 QVZLKSYUYZTETK-UHFFFAOYSA-N 0.000 description 1
- WKLZIFNOJMQEHY-UHFFFAOYSA-N methyl 3-tert-butyl-5-(3,4-dichlorobenzoyl)-2-methoxy-6-methylbenzoate Chemical compound CC(C)(C)C1=C(OC)C(C(=O)OC)=C(C)C(C(=O)C=2C=C(Cl)C(Cl)=CC=2)=C1 WKLZIFNOJMQEHY-UHFFFAOYSA-N 0.000 description 1
- XCZRAAAUBUGEJU-UHFFFAOYSA-N methyl 3-tert-butyl-5-[n'-(4-chlorobenzoyl)oxycarbamimidoyl]-2-methoxy-6-methylbenzoate Chemical compound CC(C)(C)C1=C(OC)C(C(=O)OC)=C(C)C(C(N)=NOC(=O)C=2C=CC(Cl)=CC=2)=C1 XCZRAAAUBUGEJU-UHFFFAOYSA-N 0.000 description 1
- HLYGPTSOQSVILR-UHFFFAOYSA-N methyl 3-tert-butyl-5-cyano-2-methoxy-6-methylbenzoate Chemical compound COC(=O)C1=C(C)C(C#N)=CC(C(C)(C)C)=C1OC HLYGPTSOQSVILR-UHFFFAOYSA-N 0.000 description 1
- DJLKLKHIPLKLRW-UHFFFAOYSA-N methyl 3-tert-butyl-5-isoquinolin-4-yl-2-methoxy-6-methylbenzoate Chemical compound CC(C)(C)C1=C(OC)C(C(=O)OC)=C(C)C(C=2C3=CC=CC=C3C=NC=2)=C1 DJLKLKHIPLKLRW-UHFFFAOYSA-N 0.000 description 1
- XUDLXLIYBCZTQJ-UHFFFAOYSA-N methyl 5-(1-benzothiophen-2-yl)-3-tert-butyl-2-methoxy-6-methylbenzoate Chemical compound CC(C)(C)C1=C(OC)C(C(=O)OC)=C(C)C(C=2SC3=CC=CC=C3C=2)=C1 XUDLXLIYBCZTQJ-UHFFFAOYSA-N 0.000 description 1
- BIESPOWEIOTTND-UHFFFAOYSA-N methyl 5-chloro-2-methoxy-3-phenylbenzoate Chemical compound COC(=O)C1=CC(Cl)=CC(C=2C=CC=CC=2)=C1OC BIESPOWEIOTTND-UHFFFAOYSA-N 0.000 description 1
- 150000005217 methyl ethers Chemical class 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
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- 235000019799 monosodium phosphate Nutrition 0.000 description 1
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- VGGNVBNNVSIGKG-UHFFFAOYSA-N n,n,2-trimethylaziridine-1-carboxamide Chemical compound CC1CN1C(=O)N(C)C VGGNVBNNVSIGKG-UHFFFAOYSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
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- HUMMCEUVDBVXTQ-UHFFFAOYSA-N naphthalen-1-ylboronic acid Chemical compound C1=CC=C2C(B(O)O)=CC=CC2=C1 HUMMCEUVDBVXTQ-UHFFFAOYSA-N 0.000 description 1
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- SEXOVMIIVBKGGM-UHFFFAOYSA-N naphthalene-1-thiol Chemical compound C1=CC=C2C(S)=CC=CC2=C1 SEXOVMIIVBKGGM-UHFFFAOYSA-N 0.000 description 1
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- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
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- BHMBVRSPMRCCGG-UHFFFAOYSA-N prostaglandine D2 Natural products CCCCCC(O)C=CC1C(CC=CCCCC(O)=O)C(O)CC1=O BHMBVRSPMRCCGG-UHFFFAOYSA-N 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- ABMYEXAYWZJVOV-UHFFFAOYSA-N pyridin-3-ylboronic acid Chemical compound OB(O)C1=CC=CN=C1 ABMYEXAYWZJVOV-UHFFFAOYSA-N 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- YGDICLRMNDWZAK-UHFFFAOYSA-N quinolin-3-ylboronic acid Chemical compound C1=CC=CC2=CC(B(O)O)=CN=C21 YGDICLRMNDWZAK-UHFFFAOYSA-N 0.000 description 1
- NWIJBOCPTGHGIK-UHFFFAOYSA-N quinolin-5-ylboronic acid Chemical compound C1=CC=C2C(B(O)O)=CC=CC2=N1 NWIJBOCPTGHGIK-UHFFFAOYSA-N 0.000 description 1
- JLOLSBLXNMVKGY-UHFFFAOYSA-N quinolin-6-ylboronic acid Chemical compound N1=CC=CC2=CC(B(O)O)=CC=C21 JLOLSBLXNMVKGY-UHFFFAOYSA-N 0.000 description 1
- KXJJSKYICDAICD-UHFFFAOYSA-N quinolin-8-ylboronic acid Chemical compound C1=CN=C2C(B(O)O)=CC=CC2=C1 KXJJSKYICDAICD-UHFFFAOYSA-N 0.000 description 1
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- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 229910052979 sodium sulfide Inorganic materials 0.000 description 1
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
- VGTPCRGMBIAPIM-UHFFFAOYSA-M sodium thiocyanate Chemical compound [Na+].[S-]C#N VGTPCRGMBIAPIM-UHFFFAOYSA-M 0.000 description 1
- 238000000956 solid--liquid extraction Methods 0.000 description 1
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- 229960005322 streptomycin Drugs 0.000 description 1
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- 125000003107 substituted aryl group Chemical group 0.000 description 1
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- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
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- 238000006365 thiocyanation reaction Methods 0.000 description 1
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- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 description 1
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- XFHPRJKZBJUJOO-UHFFFAOYSA-N trifluoromethyl 3-phenylbenzoate Chemical compound FC(F)(F)OC(=O)C=1C=C(C=CC=1)C1=CC=CC=C1 XFHPRJKZBJUJOO-UHFFFAOYSA-N 0.000 description 1
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- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/62—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C63/00—Compounds having carboxyl groups bound to a carbon atoms of six-membered aromatic rings
- C07C63/04—Monocyclic monocarboxylic acids
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- A—HUMAN NECESSITIES
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/45—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by at least one doubly—bound oxygen atom, not being part of a —CHO group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/52—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
- C07C229/54—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C229/64—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring the carbon skeleton being further substituted by singly-bound oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/32—Oximes
- C07C251/34—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
- C07C251/48—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with the carbon atom of at least one of the oxyimino groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
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| JP2010100552A (ja) * | 2008-10-22 | 2010-05-06 | Tosoh Corp | 1,3,5−トリアジン化合物の製造方法 |
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| US10287282B2 (en) | 2014-12-31 | 2019-05-14 | Angion Biomedica Corp. | Methods and agents for treating disease |
| CN109942427B (zh) * | 2019-04-17 | 2022-02-18 | 云南农业大学 | 一种单萜酚类衍生物及其合成方法和在农药中的应用 |
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| JP2008540520A (ja) | 2008-11-20 |
| WO2006121390A8 (en) | 2007-11-15 |
| EP1890993A4 (en) | 2010-09-08 |
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