SK180699A3 - HYDRAZINE DERIVATIVES, PREAPARATION PROCESS THEREOF, ITS USE ANDì (54) PHARMACEUTICAL COMPOSITION COMTAINING IT - Google Patents
HYDRAZINE DERIVATIVES, PREAPARATION PROCESS THEREOF, ITS USE ANDì (54) PHARMACEUTICAL COMPOSITION COMTAINING IT Download PDFInfo
- Publication number
- SK180699A3 SK180699A3 SK1806-99A SK180699A SK180699A3 SK 180699 A3 SK180699 A3 SK 180699A3 SK 180699 A SK180699 A SK 180699A SK 180699 A3 SK180699 A3 SK 180699A3
- Authority
- SK
- Slovakia
- Prior art keywords
- solvent
- butenyl
- phenyl
- methanesulfonyl
- methyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 32
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 13
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical class NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 title description 8
- -1 cyano, amino, hydroxy Chemical group 0.000 claims abstract description 470
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 89
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 66
- 125000003118 aryl group Chemical group 0.000 claims abstract description 45
- 150000002429 hydrazines Chemical class 0.000 claims abstract description 42
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 38
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 23
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 17
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 13
- 239000001257 hydrogen Substances 0.000 claims abstract description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 10
- 208000032843 Hemorrhage Diseases 0.000 claims abstract description 8
- 206010061218 Inflammation Diseases 0.000 claims abstract description 8
- 201000004681 Psoriasis Diseases 0.000 claims abstract description 8
- 206010037660 Pyrexia Diseases 0.000 claims abstract description 8
- 206010040047 Sepsis Diseases 0.000 claims abstract description 8
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 8
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 8
- 230000004054 inflammatory process Effects 0.000 claims abstract description 8
- 201000006417 multiple sclerosis Diseases 0.000 claims abstract description 8
- 201000008482 osteoarthritis Diseases 0.000 claims abstract description 8
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 7
- 206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 7
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 6
- 125000006850 spacer group Chemical group 0.000 claims abstract description 6
- 125000002252 acyl group Chemical group 0.000 claims abstract description 5
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 5
- 125000006517 heterocyclyl carbonyl group Chemical group 0.000 claims abstract description 5
- JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims abstract description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 100
- 150000001875 compounds Chemical class 0.000 claims description 58
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
- PJBQYCIDGYKEMN-UHFFFAOYSA-N pentanehydrazide Chemical compound CCCCC(=O)NN PJBQYCIDGYKEMN-UHFFFAOYSA-N 0.000 claims description 22
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 14
- 125000006239 protecting group Chemical group 0.000 claims description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 7
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 5
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 5
- BACZSFOSMGICGM-WQEUXLNQSA-N (2s,3r)-n-hydroxy-5-methyl-3-[[2-methylpropyl(methylsulfonyl)amino]carbamoyl]-2-[(e)-3-phenylprop-2-enyl]hexanamide Chemical compound CC(C)CN(S(C)(=O)=O)NC(=O)[C@H](CC(C)C)[C@@H](C(=O)NO)C\C=C\C1=CC=CC=C1 BACZSFOSMGICGM-WQEUXLNQSA-N 0.000 claims description 4
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 4
- MSFVDZMTLMMTCI-WQEUXLNQSA-N methyl n-[[(e,2r,3s)-3-(hydroxycarbamoyl)-2-(2-methylpropyl)-6-phenylhex-5-enoyl]amino]-n-(2-methylpropyl)carbamate Chemical compound COC(=O)N(CC(C)C)NC(=O)[C@H](CC(C)C)[C@@H](C(=O)NO)C\C=C\C1=CC=CC=C1 MSFVDZMTLMMTCI-WQEUXLNQSA-N 0.000 claims description 4
- 125000003368 amide group Chemical group 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 239000000543 intermediate Substances 0.000 claims description 3
- 125000005544 phthalimido group Chemical group 0.000 claims description 3
- QDPZFEJNJGEFBC-ONAORTGXSA-N (2s,3r)-n-hydroxy-5-methyl-3-[(n-methylsulfonylanilino)carbamoyl]-2-[(e)-3-phenylprop-2-enyl]hexanamide Chemical compound C([C@@H]([C@@H](CC(C)C)C(=O)NN(C=1C=CC=CC=1)S(C)(=O)=O)C(=O)NO)\C=C\C1=CC=CC=C1 QDPZFEJNJGEFBC-ONAORTGXSA-N 0.000 claims description 2
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 239000013543 active substance Substances 0.000 claims description 2
- 239000012876 carrier material Substances 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 claims description 2
- 208000025747 Rheumatic disease Diseases 0.000 claims 1
- 206010003246 arthritis Diseases 0.000 claims 1
- 230000000552 rheumatic effect Effects 0.000 claims 1
- 210000004027 cell Anatomy 0.000 abstract description 13
- 239000003814 drug Substances 0.000 abstract description 6
- 210000002510 keratinocyte Anatomy 0.000 abstract description 6
- 230000035755 proliferation Effects 0.000 abstract description 6
- 150000003950 cyclic amides Chemical class 0.000 abstract description 2
- 229940124530 sulfonamide Drugs 0.000 abstract description 2
- GOZMBJCYMQQACI-UHFFFAOYSA-N 6,7-dimethyl-3-[[methyl-[2-[methyl-[[1-[3-(trifluoromethyl)phenyl]indol-3-yl]methyl]amino]ethyl]amino]methyl]chromen-4-one;dihydrochloride Chemical compound Cl.Cl.C=1OC2=CC(C)=C(C)C=C2C(=O)C=1CN(C)CCN(C)CC(C1=CC=CC=C11)=CN1C1=CC=CC(C(F)(F)F)=C1 GOZMBJCYMQQACI-UHFFFAOYSA-N 0.000 abstract 1
- 102000009618 Transforming Growth Factors Human genes 0.000 abstract 1
- 108010009583 Transforming Growth Factors Proteins 0.000 abstract 1
- 102000018594 Tumour necrosis factor Human genes 0.000 abstract 1
- 108050007852 Tumour necrosis factor Proteins 0.000 abstract 1
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 abstract 1
- 239000002904 solvent Substances 0.000 description 768
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 546
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 279
- 239000007787 solid Substances 0.000 description 265
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 222
- 239000000243 solution Substances 0.000 description 192
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 165
- 239000007858 starting material Substances 0.000 description 164
- 238000004128 high performance liquid chromatography Methods 0.000 description 140
- 230000014759 maintenance of location Effects 0.000 description 139
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 138
- 238000010828 elution Methods 0.000 description 137
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 123
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 108
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 76
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 73
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 71
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 70
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 69
- 239000000203 mixture Substances 0.000 description 61
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 58
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 55
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 49
- 239000011541 reaction mixture Substances 0.000 description 47
- 238000006243 chemical reaction Methods 0.000 description 45
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 45
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 32
- 229910052757 nitrogen Inorganic materials 0.000 description 32
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 32
- 235000017557 sodium bicarbonate Nutrition 0.000 description 32
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 31
- 239000000741 silica gel Substances 0.000 description 31
- 229910002027 silica gel Inorganic materials 0.000 description 31
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 27
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- 239000003921 oil Substances 0.000 description 26
- 235000019198 oils Nutrition 0.000 description 26
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 24
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 22
- 239000003480 eluent Substances 0.000 description 22
- 238000003818 flash chromatography Methods 0.000 description 21
- 238000012360 testing method Methods 0.000 description 20
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 20
- 238000003756 stirring Methods 0.000 description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- 239000012074 organic phase Substances 0.000 description 18
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 16
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 16
- AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 description 16
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 16
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 16
- 238000001704 evaporation Methods 0.000 description 16
- 230000008020 evaporation Effects 0.000 description 16
- 239000000047 product Substances 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000010410 layer Substances 0.000 description 15
- 239000006260 foam Substances 0.000 description 14
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 13
- 125000005518 carboxamido group Chemical group 0.000 description 13
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 13
- 235000019341 magnesium sulphate Nutrition 0.000 description 13
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 12
- 239000012267 brine Substances 0.000 description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 12
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 12
- 239000002253 acid Substances 0.000 description 11
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 11
- MSUKPVIQZXCNNQ-MHJFOBGBSA-N (2S)-2-(methanesulfonamidocarbamoyl)-N-(oxan-2-yloxy)-3-(2-phenylpropan-2-yl)hept-4-enamide Chemical compound O1C(CCCC1)ONC(=O)[C@H](C(=O)NNS(=O)(=O)C)C(C(C)(C)C1=CC=CC=C1)C=CCC MSUKPVIQZXCNNQ-MHJFOBGBSA-N 0.000 description 10
- KPWQPKZCNKGDNE-UVMYWSIASA-N (2s,3r)-3-(methanesulfonamidocarbamoyl)-5-methyl-n-(oxan-2-yloxy)-2-[(e)-3-phenylprop-2-enyl]hexanamide Chemical compound C([C@@H]([C@@H](CC(C)C)C(=O)NNS(C)(=O)=O)C(=O)NOC1OCCCC1)\C=C\C1=CC=CC=C1 KPWQPKZCNKGDNE-UVMYWSIASA-N 0.000 description 10
- CSNDPGHMQACDKL-UHFFFAOYSA-N 4-methyl-2-methylsulfonylpentanehydrazide Chemical compound CC(C)CC(S(C)(=O)=O)C(=O)NN CSNDPGHMQACDKL-UHFFFAOYSA-N 0.000 description 10
- 125000004432 carbon atom Chemical group C* 0.000 description 10
- 239000003054 catalyst Substances 0.000 description 10
- 238000004587 chromatography analysis Methods 0.000 description 10
- 239000006071 cream Substances 0.000 description 10
- 239000003960 organic solvent Substances 0.000 description 10
- 239000012071 phase Substances 0.000 description 10
- 229910052717 sulfur Inorganic materials 0.000 description 10
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 8
- UQSZJFDIZOKCFB-UHFFFAOYSA-N 4-methyl-n'-methylsulfonylpentanehydrazide Chemical compound CC(C)CCC(=O)NNS(C)(=O)=O UQSZJFDIZOKCFB-UHFFFAOYSA-N 0.000 description 8
- VOBMACGBVNTRGF-UHFFFAOYSA-N 4-methylpentanehydrazide Chemical compound CC(C)CCC(=O)NN VOBMACGBVNTRGF-UHFFFAOYSA-N 0.000 description 8
- 102100040247 Tumor necrosis factor Human genes 0.000 description 8
- 230000001133 acceleration Effects 0.000 description 8
- 239000000969 carrier Substances 0.000 description 8
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 8
- 229940098779 methanesulfonic acid Drugs 0.000 description 8
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 7
- XZBWAJOKQNQHPP-UHFFFAOYSA-N 2-phenylpentanehydrazide Chemical compound CCCC(C(=O)NN)C1=CC=CC=C1 XZBWAJOKQNQHPP-UHFFFAOYSA-N 0.000 description 7
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 7
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 7
- 238000005859 coupling reaction Methods 0.000 description 7
- 150000008282 halocarbons Chemical class 0.000 description 7
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 6
- NGSOWKPBNFOQCR-UHFFFAOYSA-N 2-methylpropylhydrazine Chemical compound CC(C)CNN NGSOWKPBNFOQCR-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
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
- 235000011121 sodium hydroxide Nutrition 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 5
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 5
- 230000008878 coupling Effects 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical compound OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 5
- LSACYLWPPQLVSM-UHFFFAOYSA-N isobutyric acid anhydride Chemical compound CC(C)C(=O)OC(=O)C(C)C LSACYLWPPQLVSM-UHFFFAOYSA-N 0.000 description 5
- NLXXVSKHVGDQAT-UHFFFAOYSA-N o-(oxan-2-yl)hydroxylamine Chemical compound NOC1CCCCO1 NLXXVSKHVGDQAT-UHFFFAOYSA-N 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
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- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
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- 239000006188 syrup Substances 0.000 description 1
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- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- LLXBIZZVEHFSCL-SJORKVTESA-N tert-butyl (2r,3r)-2-(aminomethyl)-5-methyl-3-[(n-methylsulfonylanilino)carbamoyl]hexanoate Chemical compound CC(C)(C)OC(=O)[C@@H](CN)[C@@H](CC(C)C)C(=O)NN(S(C)(=O)=O)C1=CC=CC=C1 LLXBIZZVEHFSCL-SJORKVTESA-N 0.000 description 1
- FTSJMQPJJZHTOV-RBUKOAKNSA-N tert-butyl (2s)-5-methyl-2-[(2r)-4-methyl-1-[2-(2-methylpropyl)-2-methylsulfonylhydrazinyl]-1-oxopentan-2-yl]hex-4-enoate Chemical compound CC(C)=CC[C@H](C(=O)OC(C)(C)C)[C@@H](CC(C)C)C(=O)NN(CC(C)C)S(C)(=O)=O FTSJMQPJJZHTOV-RBUKOAKNSA-N 0.000 description 1
- YZGLGBBVCMXEOP-PXUCQJMWSA-N tert-butyl (2s,3r)-3-(anilinocarbamoyl)-5-methyl-2-[(e)-3-phenylprop-2-enyl]hexanoate Chemical compound C([C@@H]([C@@H](CC(C)C)C(=O)NNC=1C=CC=CC=1)C(=O)OC(C)(C)C)\C=C\C1=CC=CC=C1 YZGLGBBVCMXEOP-PXUCQJMWSA-N 0.000 description 1
- JMAVYZIHRVUGCZ-BDPQSKBNSA-N tert-butyl (2s,3r)-3-[(1,3-dioxoisoindol-2-yl)carbamoyl]-5-methyl-2-[(e)-3-phenylprop-2-enyl]hexanoate Chemical compound C([C@@H]([C@@H](CC(C)C)C(=O)NN1C(C2=CC=CC=C2C1=O)=O)C(=O)OC(C)(C)C)\C=C\C1=CC=CC=C1 JMAVYZIHRVUGCZ-BDPQSKBNSA-N 0.000 description 1
- YIAJOOZDZWBTDU-WCWNVHNDSA-N tert-butyl (2s,3r)-3-[(2,6-dioxopiperidin-1-yl)carbamoyl]-5-methyl-2-[(e)-3-phenylprop-2-enyl]hexanoate Chemical compound C([C@@H]([C@@H](CC(C)C)C(=O)NN1C(CCCC1=O)=O)C(=O)OC(C)(C)C)\C=C\C1=CC=CC=C1 YIAJOOZDZWBTDU-WCWNVHNDSA-N 0.000 description 1
- DOMYQMVZHSZKTN-PJVGJAJDSA-N tert-butyl (2s,3r)-3-[[benzyl(butylsulfonyl)amino]carbamoyl]-5-methyl-2-[(e)-3-phenylprop-2-enyl]hexanoate Chemical compound O=C([C@H](CC(C)C)[C@H](C\C=C\C=1C=CC=CC=1)C(=O)OC(C)(C)C)NN(S(=O)(=O)CCCC)CC1=CC=CC=C1 DOMYQMVZHSZKTN-PJVGJAJDSA-N 0.000 description 1
- BHUNPCSPRNJRHB-UEVQAURSSA-N tert-butyl (2s,3r)-3-[[methoxycarbonyl(2-methylpropyl)amino]carbamoyl]-5-methyl-2-[(e)-3-phenylprop-2-enyl]hexanoate Chemical compound COC(=O)N(CC(C)C)NC(=O)[C@H](CC(C)C)[C@@H](C(=O)OC(C)(C)C)C\C=C\C1=CC=CC=C1 BHUNPCSPRNJRHB-UEVQAURSSA-N 0.000 description 1
- BMAFKNYKRSPKRB-RTWAWAEBSA-N tert-butyl (2s,3r)-5-methyl-3-[[2-methylpropyl(methylsulfonyl)amino]carbamoyl]-2-(phenylsulfanylmethyl)hexanoate Chemical compound CC(C)CN(S(C)(=O)=O)NC(=O)[C@H](CC(C)C)[C@@H](C(=O)OC(C)(C)C)CSC1=CC=CC=C1 BMAFKNYKRSPKRB-RTWAWAEBSA-N 0.000 description 1
- CZHMLZHMOCLWCK-OAHLLOKOSA-N tert-butyl (3r)-5-methyl-2-methylidene-3-[[2-methylpropyl(methylsulfonyl)amino]carbamoyl]hexanoate Chemical compound CC(C)(C)OC(=O)C(=C)[C@@H](CC(C)C)C(=O)NN(CC(C)C)S(C)(=O)=O CZHMLZHMOCLWCK-OAHLLOKOSA-N 0.000 description 1
- ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical group CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
- DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-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
- MUQNAPSBHXFMHT-UHFFFAOYSA-N tert-butylhydrazine Chemical compound CC(C)(C)NN MUQNAPSBHXFMHT-UHFFFAOYSA-N 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- OVRJVKCZJCNSOW-UHFFFAOYSA-N thian-4-one Chemical compound O=C1CCSCC1 OVRJVKCZJCNSOW-UHFFFAOYSA-N 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
- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 1
- VNNLHYZDXIBHKZ-UHFFFAOYSA-N thiophene-2-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CS1 VNNLHYZDXIBHKZ-UHFFFAOYSA-N 0.000 description 1
- LDJBOXSVVWHBLS-UHFFFAOYSA-M triphenyl(1,3-thiazol-2-ylmethyl)phosphanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)CC1=NC=CS1 LDJBOXSVVWHBLS-UHFFFAOYSA-M 0.000 description 1
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 229940046728 tumor necrosis factor alpha inhibitor Drugs 0.000 description 1
- 239000002451 tumor necrosis factor inhibitor Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/325—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
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- 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
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- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C243/00—Compounds containing chains of nitrogen atoms singly-bound to each other, e.g. hydrazines, triazanes
- C07C243/24—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids
- C07C243/26—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids with acylating carboxyl groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C243/28—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids with acylating carboxyl groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of a saturated carbon skeleton
-
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C243/00—Compounds containing chains of nitrogen atoms singly-bound to each other, e.g. hydrazines, triazanes
- C07C243/24—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids
- C07C243/26—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids with acylating carboxyl groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C243/30—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids with acylating carboxyl groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of an unsaturated carbon skeleton
- C07C243/32—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids with acylating carboxyl groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of an unsaturated carbon skeleton the carbon skeleton containing rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
- C07C259/06—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
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- C—CHEMISTRY; METALLURGY
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/48—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups having nitrogen atoms of sulfonamide groups further bound to another hetero atom
- C07C311/49—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups having nitrogen atoms of sulfonamide groups further bound to another hetero atom to nitrogen atoms
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
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- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/38—Halogen atoms or nitro radicals
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/42—Radicals substituted by singly-bound nitrogen atoms having hetero atoms attached to the substituent nitrogen atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/76—Nitrogen atoms to which a second hetero atom is attached
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
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- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
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- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
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- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
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- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
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- Orthopedic Medicine & Surgery (AREA)
- Immunology (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Steroid Compounds (AREA)
- Paints Or Removers (AREA)
- Non-Silver Salt Photosensitive Materials And Non-Silver Salt Photography (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Hydrogenated Pyridines (AREA)
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Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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GBGB9713833.3A GB9713833D0 (en) | 1997-06-30 | 1997-06-30 | Novel hydrazine derivatives |
GBGB9803335.0A GB9803335D0 (en) | 1997-06-30 | 1998-02-17 | Novel hydrazine derivatives |
PCT/EP1998/003683 WO1999001428A1 (en) | 1997-06-30 | 1998-06-18 | Hydrazine derivatives |
Publications (1)
Publication Number | Publication Date |
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SK180699A3 true SK180699A3 (en) | 2000-09-12 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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SK1806-99A SK180699A3 (en) | 1997-06-30 | 1998-06-18 | HYDRAZINE DERIVATIVES, PREAPARATION PROCESS THEREOF, ITS USE ANDì (54) PHARMACEUTICAL COMPOSITION COMTAINING IT |
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US (1) | US6235787B1 (pt) |
EP (1) | EP0993442B1 (pt) |
JP (1) | JP3801653B2 (pt) |
CN (1) | CN1161331C (pt) |
AT (1) | ATE238277T1 (pt) |
AU (1) | AU725039B2 (pt) |
BG (1) | BG104050A (pt) |
BR (1) | BR9810952A (pt) |
CA (1) | CA2295062A1 (pt) |
DE (2) | DE69813815T2 (pt) |
DK (1) | DK0993442T3 (pt) |
ES (2) | ES2195365T3 (pt) |
FR (1) | FR2765219B1 (pt) |
GB (1) | GB2326881A (pt) |
HU (1) | HUP0002424A3 (pt) |
ID (1) | ID24705A (pt) |
IL (1) | IL133712A0 (pt) |
IS (1) | IS5322A (pt) |
IT (1) | IT1301792B1 (pt) |
MA (1) | MA26517A1 (pt) |
NO (1) | NO996534L (pt) |
NZ (1) | NZ501455A (pt) |
PL (1) | PL337793A1 (pt) |
PT (1) | PT993442E (pt) |
SK (1) | SK180699A3 (pt) |
TR (1) | TR199903281T2 (pt) |
WO (1) | WO1999001428A1 (pt) |
Families Citing this family (33)
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WO1999040063A1 (fr) * | 1998-02-06 | 1999-08-12 | Yoshitomi Pharmaceutical Industries, Ltd. | Nouveaux derives de l'acide hydroxamique de type azapeptide |
US6239151B1 (en) | 1998-06-26 | 2001-05-29 | Hoffmann-La Roche Inc. | Compounds as inhibitor of tumor necrosis factor alpha release |
GB9826153D0 (en) * | 1998-11-27 | 1999-01-20 | Hoffmann La Roche | Hydrazine derivatives |
CA2353924A1 (en) * | 1998-12-11 | 2000-06-22 | F. Hoffmann-La Roche Ag | Cyclic hydrazine derivatives as tnf-alpha inhibitors |
US20040122011A1 (en) * | 1998-12-23 | 2004-06-24 | Pharmacia Corporation | Method of using a COX-2 inhibitor and a TACE inhibitors as a combination therapy |
KR100465353B1 (ko) * | 1999-04-22 | 2005-01-13 | 주식회사유한양행 | 하이드라진 유도체 및 그의 제조방법 |
US6808902B1 (en) | 1999-11-12 | 2004-10-26 | Amgen Inc. | Process for correction of a disulfide misfold in IL-1Ra Fc fusion molecules |
RS54274B1 (en) | 2001-06-26 | 2016-02-29 | Amgen Fremont Inc. | Opgl antibodies |
TWI297335B (en) * | 2001-07-10 | 2008-06-01 | Synta Pharmaceuticals Corp | Taxol enhancer compounds |
US6924312B2 (en) * | 2001-07-10 | 2005-08-02 | Synta Pharmaceuticals Corp. | Taxol enhancer compounds |
TWI252847B (en) * | 2001-07-10 | 2006-04-11 | Synta Pharmaceuticals Corp | Synthesis of taxol enhancers |
TWI332943B (en) * | 2001-07-10 | 2010-11-11 | Synta Pharmaceuticals Corp | Taxol enhancer compounds |
UY27813A1 (es) * | 2002-05-31 | 2003-12-31 | Smithkline Beecham Corp | Inhibidores de la peptido-desformilasa |
GB0229673D0 (en) * | 2002-12-19 | 2003-01-29 | British Biotech Pharm | Antibacterial agents |
EP1578782A4 (en) | 2002-12-30 | 2007-09-12 | Amgen Inc | COSTIMULATING FACTORIAL THERAPY |
TWI330079B (en) * | 2003-01-15 | 2010-09-11 | Synta Pharmaceuticals Corp | Treatment for cancers |
UA89035C2 (ru) | 2003-12-03 | 2009-12-25 | Лео Фарма А/С | Эфиры гидроксамовых кислот и их фармацевтическое применение |
CN1993318B (zh) | 2004-06-23 | 2012-10-03 | Synta医药公司 | 用于治疗癌症的双(硫代-酰肼酰胺)盐 |
WO2006055747A2 (en) * | 2004-11-19 | 2006-05-26 | Synta Pharmaceuticals Corp. | Bis(thio-hydrazide amides) for increasing hsp70 expression |
WO2006101937A1 (en) * | 2005-03-18 | 2006-09-28 | Janssen Pharmaceutica N.V. | Acylhydrazones as kinase modulators |
JP2008536875A (ja) * | 2005-04-15 | 2008-09-11 | シンタ ファーマシューティカルズ コーポレーション | ビス(チオヒドラジド)アミド化合物による併用癌療法 |
AU2006247470B2 (en) | 2005-05-16 | 2010-04-01 | Synta Pharmaceuticals Corp. | Synthesis of bis(thio-hydrazide amide) salts |
DE102005038344A1 (de) * | 2005-08-13 | 2007-02-15 | Tetra Laval Holdings & Finance S.A. | Vorrichtung zum Ultraschallbearbeiten von Werkstücken |
EP1940375A1 (en) * | 2005-08-16 | 2008-07-09 | Synta Pharmaceuticals Corporation | Bis(thio-hydrazide amide) formulation |
EP2041181B1 (en) * | 2006-06-08 | 2011-05-18 | Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) | Specific protease inhibitors and their use in cancer therapy |
SG174087A1 (en) | 2006-08-21 | 2011-09-29 | Synta Pharmaceuticals Corp | Compounds for treating proliferative disorders |
WO2008027445A2 (en) * | 2006-08-31 | 2008-03-06 | Synta Pharmaceuticals Corp. | Combination with bis(thiohydrazide amides) for treating cancer |
US7645904B2 (en) * | 2006-09-15 | 2010-01-12 | Synta Pharmaceuticals Corp. | Purification of bis(thiohydrazide amides) |
TW200838501A (en) * | 2007-02-02 | 2008-10-01 | Theravance Inc | Dual-acting antihypertensive agents |
CN102153490A (zh) * | 2011-02-16 | 2011-08-17 | 东营柯林维尔化工有限公司 | 肼基甲酸酯类的合成 |
WO2014019092A1 (en) | 2012-08-01 | 2014-02-06 | The Hospital For Sick Children | Inhibitors of peptidyl arginine deiminase (pad) enzymes and uses thereof |
CN104031081B (zh) * | 2014-03-06 | 2017-03-29 | 苏州大学 | 一种多酰胺抗菌剂、制备方法及其应用 |
CR20210578A (es) * | 2019-04-30 | 2022-02-22 | Sitryx Therapeutics Ltd | Derivados de ácido itacónico y usos de estos en el tratamiento de una enfermedad inflamatoria asociada con una respuesta inmunotaria indeseable |
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CA2058797A1 (en) | 1991-02-01 | 1992-08-02 | Michael John Broadhurst | Amino acid derivatives |
US5399589A (en) | 1992-12-17 | 1995-03-21 | Basf Aktiengesellschaft | Oxalyl hydrazide-hydroxamic acid derivatives, their preparation and their use as fungicides |
WO1999040063A1 (fr) | 1998-02-06 | 1999-08-12 | Yoshitomi Pharmaceutical Industries, Ltd. | Nouveaux derives de l'acide hydroxamique de type azapeptide |
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1998
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- 1998-06-18 JP JP50623099A patent/JP3801653B2/ja not_active Expired - Fee Related
- 1998-06-18 IL IL13371298A patent/IL133712A0/xx unknown
- 1998-06-18 WO PCT/EP1998/003683 patent/WO1999001428A1/en not_active Application Discontinuation
- 1998-06-18 ID IDW991686A patent/ID24705A/id unknown
- 1998-06-18 CA CA002295062A patent/CA2295062A1/en not_active Abandoned
- 1998-06-18 TR TR1999/03281T patent/TR199903281T2/xx unknown
- 1998-06-18 DE DE69813815T patent/DE69813815T2/de not_active Expired - Fee Related
- 1998-06-18 CN CNB988075849A patent/CN1161331C/zh not_active Expired - Fee Related
- 1998-06-18 NZ NZ501455A patent/NZ501455A/en unknown
- 1998-06-18 HU HU0002424A patent/HUP0002424A3/hu unknown
- 1998-06-24 IT IT1998MI001441A patent/IT1301792B1/it active IP Right Grant
- 1998-06-26 FR FR9808124A patent/FR2765219B1/fr not_active Expired - Lifetime
- 1998-06-29 GB GB9814027A patent/GB2326881A/en not_active Withdrawn
- 1998-06-29 ES ES009801359A patent/ES2140348B1/es not_active Expired - Lifetime
- 1998-06-30 MA MA25147A patent/MA26517A1/fr unknown
- 1998-06-30 DE DE19829229A patent/DE19829229A1/de not_active Withdrawn
-
1999
- 1999-12-23 IS IS5322A patent/IS5322A/is unknown
- 1999-12-28 BG BG104050A patent/BG104050A/bg unknown
- 1999-12-29 NO NO996534A patent/NO996534L/no not_active Application Discontinuation
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