ES2865163T3 - Derivados de ácido oleanólico modificado en C4 para la inhibición de il-17 y otros usos - Google Patents
Derivados de ácido oleanólico modificado en C4 para la inhibición de il-17 y otros usos Download PDFInfo
- Publication number
- ES2865163T3 ES2865163T3 ES16781915T ES16781915T ES2865163T3 ES 2865163 T3 ES2865163 T3 ES 2865163T3 ES 16781915 T ES16781915 T ES 16781915T ES 16781915 T ES16781915 T ES 16781915T ES 2865163 T3 ES2865163 T3 ES 2865163T3
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- Prior art keywords
- substituted
- alkyl
- hydrogen
- compound
- alkoxy
- Prior art date
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- 230000005764 inhibitory process Effects 0.000 title description 6
- MIJYXULNPSFWEK-GTOFXWBISA-N 3beta-hydroxyolean-12-en-28-oic acid Chemical class C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CCC(C)(C)C[C@H]5C4=CC[C@@H]3[C@]21C MIJYXULNPSFWEK-GTOFXWBISA-N 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 410
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 130
- 239000001257 hydrogen Substances 0.000 claims abstract description 128
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 123
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 97
- 125000004423 acyloxy group Chemical group 0.000 claims abstract description 78
- 125000003118 aryl group Chemical group 0.000 claims abstract description 68
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 68
- -1 hydroxy, amino Chemical group 0.000 claims abstract description 64
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 63
- 125000004663 dialkyl amino group Chemical group 0.000 claims abstract description 59
- 125000002252 acyl group Chemical group 0.000 claims abstract description 57
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 57
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract description 53
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 46
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 40
- 125000001769 aryl amino group Chemical group 0.000 claims abstract description 40
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 39
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 39
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 37
- 125000004104 aryloxy group Chemical group 0.000 claims abstract description 37
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 36
- 239000003607 modifier Substances 0.000 claims abstract description 36
- 125000000000 cycloalkoxy group Chemical group 0.000 claims abstract description 35
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 34
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims abstract description 33
- 125000003368 amide group Chemical group 0.000 claims abstract description 32
- 125000004429 atom Chemical group 0.000 claims abstract description 32
- 150000003839 salts Chemical class 0.000 claims abstract description 31
- 125000005553 heteroaryloxy group Chemical group 0.000 claims abstract description 29
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical group [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims abstract description 24
- 125000003302 alkenyloxy group Chemical group 0.000 claims abstract description 21
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 21
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims abstract description 19
- 150000001241 acetals Chemical class 0.000 claims abstract description 19
- 125000006323 alkenyl amino group Chemical group 0.000 claims abstract description 19
- 125000001691 aryl alkyl amino group Chemical group 0.000 claims abstract description 19
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 17
- 150000002373 hemiacetals Chemical class 0.000 claims abstract description 17
- 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 15
- 125000000033 alkoxyamino group Chemical group 0.000 claims abstract description 11
- 125000005241 heteroarylamino group Chemical group 0.000 claims abstract description 11
- 125000005035 acylthio group Chemical group 0.000 claims abstract description 10
- BWOVZCWSJFYBRM-UHFFFAOYSA-N carbononitridic isocyanate Chemical group O=C=NC#N BWOVZCWSJFYBRM-UHFFFAOYSA-N 0.000 claims abstract description 8
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims abstract description 7
- 239000003513 alkali Substances 0.000 claims abstract description 4
- 125000001118 alkylidene group Chemical group 0.000 claims abstract description 4
- 125000006319 alkynyl amino group Chemical group 0.000 claims abstract description 3
- 125000006310 cycloalkyl amino group Chemical group 0.000 claims abstract description 3
- 125000003441 thioacyl group Chemical group 0.000 claims abstract description 3
- 125000001475 halogen functional group Chemical group 0.000 claims abstract 19
- 125000005277 alkyl imino group Chemical group 0.000 claims abstract 2
- 239000000203 mixture Substances 0.000 claims description 265
- 150000002431 hydrogen Chemical class 0.000 claims description 65
- 102000013691 Interleukin-17 Human genes 0.000 claims description 53
- 108050003558 Interleukin-17 Proteins 0.000 claims description 53
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 51
- 229910052799 carbon Inorganic materials 0.000 claims description 45
- 201000010099 disease Diseases 0.000 claims description 34
- 208000035475 disorder Diseases 0.000 claims description 17
- 230000000694 effects Effects 0.000 claims description 17
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- 230000002401 inhibitory effect Effects 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 3
- 101150100019 NRDC gene Proteins 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 abstract description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 5
- 101100148545 Caenorhabditis elegans snr-5 gene Proteins 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 648
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 384
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 205
- 239000000284 extract Substances 0.000 description 150
- 239000000243 solution Substances 0.000 description 138
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 117
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 110
- 238000006243 chemical reaction Methods 0.000 description 109
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 107
- 239000000741 silica gel Substances 0.000 description 105
- 229910002027 silica gel Inorganic materials 0.000 description 105
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 105
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 102
- 239000006260 foam Substances 0.000 description 100
- 238000004440 column chromatography Methods 0.000 description 97
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 88
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 84
- 239000011734 sodium Substances 0.000 description 81
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 78
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 75
- 239000007787 solid Substances 0.000 description 73
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 72
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 65
- 229920006395 saturated elastomer Polymers 0.000 description 60
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 55
- 239000003153 chemical reaction reagent Substances 0.000 description 50
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 46
- QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical compound C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 description 46
- VRLDVERQJMEPIF-UHFFFAOYSA-N dbdmh Chemical compound CC1(C)N(Br)C(=O)N(Br)C1=O VRLDVERQJMEPIF-UHFFFAOYSA-N 0.000 description 45
- 239000012267 brine Substances 0.000 description 43
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 43
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 42
- 238000003756 stirring Methods 0.000 description 41
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 37
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 36
- 238000005160 1H NMR spectroscopy Methods 0.000 description 33
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 27
- 238000000746 purification Methods 0.000 description 26
- 235000002639 sodium chloride Nutrition 0.000 description 26
- 239000007832 Na2SO4 Substances 0.000 description 25
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 25
- 229910052938 sodium sulfate Inorganic materials 0.000 description 25
- 235000011152 sodium sulphate Nutrition 0.000 description 25
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 24
- 238000000034 method Methods 0.000 description 21
- 238000011282 treatment Methods 0.000 description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 20
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 19
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 16
- 230000000670 limiting effect Effects 0.000 description 16
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
- 230000001225 therapeutic effect Effects 0.000 description 16
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 15
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 15
- 229910052757 nitrogen Inorganic materials 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 15
- 150000001721 carbon Chemical class 0.000 description 14
- 239000003795 chemical substances by application Substances 0.000 description 14
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 14
- 210000004698 lymphocyte Anatomy 0.000 description 14
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 14
- TUCNEACPLKLKNU-UHFFFAOYSA-N acetyl Chemical compound C[C]=O TUCNEACPLKLKNU-UHFFFAOYSA-N 0.000 description 13
- PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 12
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 12
- 229910000397 disodium phosphate Inorganic materials 0.000 description 12
- 235000019800 disodium phosphate Nutrition 0.000 description 12
- 239000000047 product Substances 0.000 description 12
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- 235000017557 sodium bicarbonate Nutrition 0.000 description 12
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- 238000005481 NMR spectroscopy Methods 0.000 description 11
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- 230000007170 pathology Effects 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 238000003818 flash chromatography Methods 0.000 description 10
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
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- 125000001931 aliphatic group Chemical group 0.000 description 9
- 150000001336 alkenes Chemical class 0.000 description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 9
- 125000004122 cyclic group Chemical group 0.000 description 9
- 125000005843 halogen group Chemical group 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- 125000003396 thiol group Chemical class [H]S* 0.000 description 9
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
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- 210000004027 cell Anatomy 0.000 description 8
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 8
- 235000019256 formaldehyde Nutrition 0.000 description 8
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
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- 238000010791 quenching Methods 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 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 7
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- 125000004433 nitrogen atom Chemical class N* 0.000 description 7
- 125000006413 ring segment Chemical group 0.000 description 7
- BPXKZEMBEZGUAH-UHFFFAOYSA-N 2-(chloromethoxy)ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCCl BPXKZEMBEZGUAH-UHFFFAOYSA-N 0.000 description 6
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 6
- 101150065749 Churc1 gene Proteins 0.000 description 6
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- 102100038239 Protein Churchill Human genes 0.000 description 6
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 6
- 125000002015 acyclic group Chemical group 0.000 description 6
- 238000010936 aqueous wash Methods 0.000 description 6
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
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- VCUXVXLUOHDHKK-UHFFFAOYSA-N 2-(2-aminopyrimidin-4-yl)-4-(2-chloro-4-methoxyphenyl)-1,3-thiazole-5-carboxamide Chemical compound ClC1=CC(OC)=CC=C1C1=C(C(N)=O)SC(C=2N=C(N)N=CC=2)=N1 VCUXVXLUOHDHKK-UHFFFAOYSA-N 0.000 description 5
- DFRAKBCRUYUFNT-UHFFFAOYSA-N 3,8-dicyclohexyl-2,4,7,9-tetrahydro-[1,3]oxazino[5,6-h][1,3]benzoxazine Chemical compound C1CCCCC1N1CC(C=CC2=C3OCN(C2)C2CCCCC2)=C3OC1 DFRAKBCRUYUFNT-UHFFFAOYSA-N 0.000 description 5
- RRSNDVCODIMOFX-MPKOGUQCSA-N Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O Chemical compound Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O RRSNDVCODIMOFX-MPKOGUQCSA-N 0.000 description 5
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- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 5
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- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 5
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- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical group CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
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- 208000028173 post-traumatic stress disease Diseases 0.000 description 1
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- GRJJQCWNZGRKAU-UHFFFAOYSA-N pyridin-1-ium;fluoride Chemical compound F.C1=CC=NC=C1 GRJJQCWNZGRKAU-UHFFFAOYSA-N 0.000 description 1
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- 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 1
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- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- JUJBNYBVVQSIOU-UHFFFAOYSA-M sodium;4-[2-(4-iodophenyl)-3-(4-nitrophenyl)tetrazol-2-ium-5-yl]benzene-1,3-disulfonate Chemical compound [Na+].C1=CC([N+](=O)[O-])=CC=C1N1[N+](C=2C=CC(I)=CC=2)=NC(C=2C(=CC(=CC=2)S([O-])(=O)=O)S([O-])(=O)=O)=N1 JUJBNYBVVQSIOU-UHFFFAOYSA-M 0.000 description 1
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- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
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- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J63/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
- C07J63/008—Expansion of ring D by one atom, e.g. D homo steroids
-
- 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]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- C07J71/0005—Oxygen-containing hetero ring
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pain & Pain Management (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Rheumatology (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (2)
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|---|---|---|---|
| US201562222632P | 2015-09-23 | 2015-09-23 | |
| PCT/US2016/053545 WO2017053868A1 (en) | 2015-09-23 | 2016-09-23 | C4-modified oleanolic acid derivatives for inhibition of il-17 and other uses |
Publications (1)
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|---|---|
| ES2865163T3 true ES2865163T3 (es) | 2021-10-15 |
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| ES16781915T Active ES2865163T3 (es) | 2015-09-23 | 2016-09-23 | Derivados de ácido oleanólico modificado en C4 para la inhibición de il-17 y otros usos |
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| EP (1) | EP3353190B1 (enExample) |
| JP (1) | JP7074674B2 (enExample) |
| KR (1) | KR102796889B1 (enExample) |
| CN (1) | CN108290922B (enExample) |
| AU (1) | AU2016326704B2 (enExample) |
| BR (1) | BR112018005861B1 (enExample) |
| CA (1) | CA2998681C (enExample) |
| EA (1) | EA201890767A1 (enExample) |
| ES (1) | ES2865163T3 (enExample) |
| IL (1) | IL258185B (enExample) |
| MX (1) | MX386256B (enExample) |
| NZ (1) | NZ741082A (enExample) |
| WO (1) | WO2017053868A1 (enExample) |
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| ES2703274T3 (es) | 2008-04-18 | 2019-03-07 | Reata Pharmaceuticals Inc | Moduladores de la inflamación antioxidantes: derivados del ácido oleanólico con modificaciones amino y otras en C-17 |
| DK3444261T3 (da) | 2012-04-27 | 2021-03-08 | Reata Pharmaceuticals Inc | 2,2-difluorpropionamidderivat af bardoxolonmethyl, farmaceutiske sammensætninger og polymorfer deraf til anvendelse ved behandling af visse lidelser |
| PL2892912T3 (pl) | 2012-09-10 | 2019-10-31 | Reata Pharmaceuticals Inc | C17-alkanodiylowe i alkenodiylowe pochodne kwasu oleanolowego i sposoby ich zastosowania |
| US9512094B2 (en) | 2012-09-10 | 2016-12-06 | Reata Pharmaceuticals, Inc. | C17-heteroaryl derivatives of oleanolic acid and methods of use thereof |
| TWI649330B (zh) | 2013-04-24 | 2019-02-01 | 艾伯維有限公司 | 甲基巴多索龍之２，２－二氟丙醯胺衍生物、其多晶形及其使用方法 |
| EA201890767A1 (ru) | 2015-09-23 | 2019-09-30 | Рита Фармасьютикалз, Инк. | C4-модифицированные производные олеаноловой кислоты для ингибирования il-17 и других применений |
| AU2017356955B2 (en) | 2016-11-08 | 2023-11-09 | Reata Pharmaceuticals Holdings, LLC | Methods of treating Alport syndrome using bardoxolone methyl or analogs thereof |
| CN108299541B (zh) * | 2018-01-18 | 2020-12-11 | 华南师范大学 | 海洋微生物来源的二倍半萜AsperterpinolB衍生物及合成方法与抗炎应用 |
| CN108191944B (zh) * | 2018-01-18 | 2020-12-11 | 华南师范大学 | 海洋微生物来源的二倍半萜AsperterpinolB衍生物及合成方法与糖酶应用 |
| EP3810141A1 (en) | 2018-06-20 | 2021-04-28 | Reata Pharmaceuticals, Inc. | Cysteine-dependent inverse agonists of nuclear receptors ror-gamma/ror-gamma-t and methods of treating diseases or disorders therewith |
| CN109248168A (zh) * | 2018-10-30 | 2019-01-22 | 武汉卫无忧生物科技有限公司 | 齐墩果酸在制备抗幽门螺杆菌的药物中的用途 |
| TW202214648A (zh) | 2019-01-07 | 2022-04-16 | 美商美國禮來大藥廠 | Il-17a抑制劑 |
| KR102891865B1 (ko) * | 2019-07-19 | 2025-11-26 | 리아타 파마슈티컬즈, 아이엔씨. | C17 극성-치환된 헤테로방향족 합성 트리터페노이드 및 그의 사용 방법 |
| EP4259155A1 (en) | 2020-12-11 | 2023-10-18 | Reata Pharmaceuticals Holdings, LLC | Synthetic triterpenoids for use in therapy |
| WO2022155614A1 (en) * | 2021-01-18 | 2022-07-21 | Reata Pharmaceuticals, Inc. | Synthetic ursolic acid derivatives and methods of use thereof |
| CN113185570A (zh) * | 2021-05-12 | 2021-07-30 | 张洪胜 | 一种治疗银屑病的齐墩果酸衍生物及其制备方法 |
| CN117964678A (zh) * | 2024-01-29 | 2024-05-03 | 烟台大学 | C17位杂芳族羰基修饰的齐墩果烷三萜衍生物及其制备方法和用途 |
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-
2016
- 2016-09-23 EA EA201890767A patent/EA201890767A1/ru unknown
- 2016-09-23 CN CN201680067912.8A patent/CN108290922B/zh active Active
- 2016-09-23 JP JP2018534521A patent/JP7074674B2/ja active Active
- 2016-09-23 AU AU2016326704A patent/AU2016326704B2/en active Active
- 2016-09-23 EP EP16781915.0A patent/EP3353190B1/en active Active
- 2016-09-23 WO PCT/US2016/053545 patent/WO2017053868A1/en not_active Ceased
- 2016-09-23 US US15/760,662 patent/US11584775B2/en active Active
- 2016-09-23 KR KR1020187011430A patent/KR102796889B1/ko active Active
- 2016-09-23 ES ES16781915T patent/ES2865163T3/es active Active
- 2016-09-23 NZ NZ741082A patent/NZ741082A/en unknown
- 2016-09-23 CA CA2998681A patent/CA2998681C/en active Active
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| AU2016326704A1 (en) | 2018-04-26 |
| EA201890767A1 (ru) | 2019-09-30 |
| BR112018005861B1 (pt) | 2022-11-22 |
| WO2017053868A1 (en) | 2017-03-30 |
| NZ741082A (en) | 2023-06-30 |
| CN108290922A (zh) | 2018-07-17 |
| EP3353190B1 (en) | 2021-03-17 |
| BR112018005861A2 (pt) | 2018-10-16 |
| US11584775B2 (en) | 2023-02-21 |
| IL258185A (en) | 2018-05-31 |
| CN108290922B (zh) | 2021-12-07 |
| US12545701B2 (en) | 2026-02-10 |
| KR20180061251A (ko) | 2018-06-07 |
| US20190153022A1 (en) | 2019-05-23 |
| HK1258095A1 (zh) | 2019-11-01 |
| MX2018003569A (es) | 2018-11-29 |
| KR102796889B1 (ko) | 2025-04-17 |
| US20230250130A1 (en) | 2023-08-10 |
| EP3353190A1 (en) | 2018-08-01 |
| JP7074674B2 (ja) | 2022-05-24 |
| AU2016326704B2 (en) | 2021-01-28 |
| JP2018528275A (ja) | 2018-09-27 |
| CA2998681C (en) | 2024-02-06 |
| IL258185B (en) | 2021-08-31 |
| WO2017053868A8 (en) | 2018-04-19 |
| CA2998681A1 (en) | 2017-03-30 |
| MX386256B (es) | 2025-03-18 |
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