IL119729A - Heterocyclic compounds having tachykinin receptor antagonist activity and pharmaceutical compositions containing the same - Google Patents
Heterocyclic compounds having tachykinin receptor antagonist activity and pharmaceutical compositions containing the sameInfo
- Publication number
- IL119729A IL119729A IL11972996A IL11972996A IL119729A IL 119729 A IL119729 A IL 119729A IL 11972996 A IL11972996 A IL 11972996A IL 11972996 A IL11972996 A IL 11972996A IL 119729 A IL119729 A IL 119729A
- Authority
- IL
- Israel
- Prior art keywords
- group
- groups
- carbon atoms
- doc
- dgt
- Prior art date
Links
- 230000000694 effects Effects 0.000 title description 10
- 150000002391 heterocyclic compounds Chemical class 0.000 title description 4
- 239000002462 tachykinin receptor antagonist Substances 0.000 title description 3
- 239000008194 pharmaceutical composition Substances 0.000 title description 2
- -1 sulphonyl group Chemical group 0.000 claims abstract description 607
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 287
- 150000001875 compounds Chemical class 0.000 claims abstract description 228
- 125000003118 aryl group Chemical group 0.000 claims abstract description 171
- 125000001424 substituent group Chemical group 0.000 claims abstract description 145
- 125000002837 carbocyclic group Chemical group 0.000 claims abstract description 96
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 76
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims abstract description 67
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 55
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 48
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 43
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 42
- 125000002252 acyl group Chemical group 0.000 claims abstract description 42
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 41
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 31
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 31
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 29
- 125000001931 aliphatic group Chemical group 0.000 claims abstract description 28
- 125000005843 halogen group Chemical group 0.000 claims abstract description 28
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 24
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 24
- 239000001301 oxygen Substances 0.000 claims abstract description 24
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 22
- 125000006413 ring segment Chemical group 0.000 claims abstract description 18
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 17
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 17
- 125000004442 acylamino group Chemical group 0.000 claims abstract description 15
- 125000001589 carboacyl group Chemical group 0.000 claims abstract description 12
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims abstract description 12
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 12
- 239000005864 Sulphur Substances 0.000 claims abstract description 11
- 125000004450 alkenylene group Chemical group 0.000 claims abstract description 10
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 9
- 125000004429 atom Chemical group 0.000 claims abstract description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 8
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000005155 haloalkylene group Chemical group 0.000 claims abstract description 5
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 4
- 125000001453 quaternary ammonium group Chemical group 0.000 claims abstract description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 59
- 150000002148 esters Chemical class 0.000 claims description 45
- 150000003839 salts Chemical class 0.000 claims description 28
- 125000005605 benzo group Chemical group 0.000 claims description 26
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 26
- 239000000203 mixture Substances 0.000 claims description 23
- 201000010099 disease Diseases 0.000 claims description 20
- 125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 claims description 17
- 125000003277 amino group Chemical group 0.000 claims description 15
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 13
- 238000011282 treatment Methods 0.000 claims description 8
- 206010020751 Hypersensitivity Diseases 0.000 claims description 7
- 208000027866 inflammatory disease Diseases 0.000 claims description 5
- 208000002193 Pain Diseases 0.000 claims description 4
- 230000007815 allergy Effects 0.000 claims description 4
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 4
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 4
- 230000036407 pain Effects 0.000 claims description 4
- 238000011321 prophylaxis Methods 0.000 claims description 4
- 208000023504 respiratory system disease Diseases 0.000 claims description 4
- 208000017520 skin disease Diseases 0.000 claims description 4
- 206010012335 Dependence Diseases 0.000 claims description 3
- 206010014950 Eosinophilia Diseases 0.000 claims description 3
- ATTZFSUZZUNHBP-UHFFFAOYSA-N Piperonyl sulfoxide Chemical compound CCCCCCCCS(=O)C(C)CC1=CC=C2OCOC2=C1 ATTZFSUZZUNHBP-UHFFFAOYSA-N 0.000 claims description 3
- 206010047700 Vomiting Diseases 0.000 claims description 3
- 230000002159 abnormal effect Effects 0.000 claims description 3
- 208000026935 allergic disease Diseases 0.000 claims description 3
- 230000017531 blood circulation Effects 0.000 claims description 3
- 208000015114 central nervous system disease Diseases 0.000 claims description 3
- 208000010643 digestive system disease Diseases 0.000 claims description 3
- 208000035475 disorder Diseases 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 208000024732 dysthymic disease Diseases 0.000 claims description 3
- 230000009610 hypersensitivity Effects 0.000 claims description 3
- 230000008105 immune reaction Effects 0.000 claims description 3
- 230000002434 immunopotentiative effect Effects 0.000 claims description 3
- 230000004770 neurodegeneration Effects 0.000 claims description 3
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 3
- 230000011514 reflex Effects 0.000 claims description 3
- 230000000392 somatic effect Effects 0.000 claims description 3
- 125000001174 sulfone group Chemical group 0.000 claims description 3
- 230000002889 sympathetic effect Effects 0.000 claims description 3
- 210000003932 urinary bladder Anatomy 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims 2
- FUJSJWRORKKPAI-UHFFFAOYSA-N 2-(2,4-dichlorophenoxy)acetyl chloride Chemical compound ClC(=O)COC1=CC=C(Cl)C=C1Cl FUJSJWRORKKPAI-UHFFFAOYSA-N 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 229930192474 thiophene Natural products 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 2
- 238000006243 chemical reaction Methods 0.000 description 543
- 239000002904 solvent Substances 0.000 description 277
- 239000003153 chemical reaction reagent Substances 0.000 description 210
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 150
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 129
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 110
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 104
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 102
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 96
- 239000002585 base Substances 0.000 description 92
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 90
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 72
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 67
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 66
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 64
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 60
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 57
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 56
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- 238000000034 method Methods 0.000 description 54
- 150000002170 ethers Chemical class 0.000 description 52
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 52
- 239000007858 starting material Substances 0.000 description 50
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 48
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 46
- 231100000989 no adverse effect Toxicity 0.000 description 46
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 43
- 150000008282 halocarbons Chemical class 0.000 description 39
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 36
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 36
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 36
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 35
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 34
- 150000001408 amides Chemical class 0.000 description 34
- 150000002825 nitriles Chemical class 0.000 description 34
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 33
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 33
- 239000008096 xylene Substances 0.000 description 33
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 32
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
- 229910001868 water Inorganic materials 0.000 description 32
- 239000002253 acid Substances 0.000 description 31
- 230000008569 process Effects 0.000 description 31
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 30
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 28
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 28
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 28
- 229940117389 dichlorobenzene Drugs 0.000 description 28
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 28
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 28
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 26
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 25
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 24
- 239000003795 chemical substances by application Substances 0.000 description 24
- LRDFRRGEGBBSRN-UHFFFAOYSA-N isobutyronitrile Chemical compound CC(C)C#N LRDFRRGEGBBSRN-UHFFFAOYSA-N 0.000 description 24
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 23
- 229910052783 alkali metal Inorganic materials 0.000 description 22
- 239000007800 oxidant agent Substances 0.000 description 22
- 150000001298 alcohols Chemical class 0.000 description 21
- 239000003638 chemical reducing agent Substances 0.000 description 21
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 20
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 20
- 239000003054 catalyst Substances 0.000 description 20
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 20
- 229940090181 propyl acetate Drugs 0.000 description 20
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 19
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 18
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 18
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 18
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 18
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 18
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 18
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 18
- HJOVHMDZYOCNQW-UHFFFAOYSA-N isophorone Chemical compound CC1=CC(=O)CC(C)(C)C1 HJOVHMDZYOCNQW-UHFFFAOYSA-N 0.000 description 18
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 17
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 17
- 239000003960 organic solvent Substances 0.000 description 17
- 238000007254 oxidation reaction Methods 0.000 description 17
- 150000003462 sulfoxides Chemical class 0.000 description 17
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 16
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 16
- 125000004434 sulfur atom Chemical group 0.000 description 16
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 15
- 150000007513 acids Chemical class 0.000 description 15
- 229910052751 metal Inorganic materials 0.000 description 15
- 239000002184 metal Substances 0.000 description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 15
- RGUKYNXWOWSRET-UHFFFAOYSA-N 4-pyrrolidin-1-ylpyridine Chemical compound C1CCCN1C1=CC=NC=C1 RGUKYNXWOWSRET-UHFFFAOYSA-N 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- 239000002841 Lewis acid Substances 0.000 description 14
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 14
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 14
- 150000002576 ketones Chemical class 0.000 description 14
- 150000007517 lewis acids Chemical class 0.000 description 14
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 14
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 13
- 235000011054 acetic acid Nutrition 0.000 description 13
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- 229960000583 acetic acid Drugs 0.000 description 12
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 12
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
- 150000007530 organic bases Chemical class 0.000 description 12
- 230000003647 oxidation Effects 0.000 description 12
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 12
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 12
- 125000006239 protecting group Chemical group 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 12
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 11
- 229910052763 palladium Inorganic materials 0.000 description 11
- HVHZEKKZMFRULH-UHFFFAOYSA-N 2,6-ditert-butyl-4-methylpyridine Chemical compound CC1=CC(C(C)(C)C)=NC(C(C)(C)C)=C1 HVHZEKKZMFRULH-UHFFFAOYSA-N 0.000 description 10
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 10
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 10
- 230000003197 catalytic effect Effects 0.000 description 10
- 125000004185 ester group Chemical group 0.000 description 10
- 238000006460 hydrolysis reaction Methods 0.000 description 10
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 10
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 10
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 10
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 10
- 229960005335 propanol Drugs 0.000 description 10
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 10
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- LRHPLDYGYMQRHN-UHFFFAOYSA-N Butanol Natural products CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 9
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 9
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 9
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 9
- 239000003377 acid catalyst Substances 0.000 description 9
- 229910052801 chlorine Inorganic materials 0.000 description 9
- 238000002955 isolation Methods 0.000 description 9
- 229910000027 potassium carbonate Inorganic materials 0.000 description 9
- 235000011181 potassium carbonates Nutrition 0.000 description 9
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- CXWQAPHDSYDHBR-UHFFFAOYSA-N piperidine-4-carboxamide Chemical compound NC(=O)C1CCNCC1.NC(=O)C1CCNCC1 CXWQAPHDSYDHBR-UHFFFAOYSA-N 0.000 description 4
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
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- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 3
- 238000001311 chemical methods and process Methods 0.000 description 3
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 3
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- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 3
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- RCBVKBFIWMOMHF-UHFFFAOYSA-L hydroxy-(hydroxy(dioxo)chromio)oxy-dioxochromium;pyridine Chemical compound C1=CC=NC=C1.C1=CC=NC=C1.O[Cr](=O)(=O)O[Cr](O)(=O)=O RCBVKBFIWMOMHF-UHFFFAOYSA-L 0.000 description 3
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- 125000001841 imino group Chemical group [H]N=* 0.000 description 3
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- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 description 3
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- 238000007796 conventional method Methods 0.000 description 2
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- 125000000628 margaroyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- BLLFVUPNHCTMSV-UHFFFAOYSA-N methyl nitrite Chemical compound CON=O BLLFVUPNHCTMSV-UHFFFAOYSA-N 0.000 description 1
- LSEFCHWGJNHZNT-UHFFFAOYSA-M methyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 LSEFCHWGJNHZNT-UHFFFAOYSA-M 0.000 description 1
- JNMIXMFEVJHFNY-UHFFFAOYSA-M methyl(triphenyl)phosphanium;iodide Chemical compound [I-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 JNMIXMFEVJHFNY-UHFFFAOYSA-M 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 229910052750 molybdenum Inorganic materials 0.000 description 1
- 239000011733 molybdenum Substances 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 125000001419 myristoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- YHHNXMTTWKAUEQ-UHFFFAOYSA-N n-(4-methylphenyl)-2,2-diphenylethenimine Chemical compound C1=CC(C)=CC=C1N=C=C(C=1C=CC=CC=1)C1=CC=CC=C1 YHHNXMTTWKAUEQ-UHFFFAOYSA-N 0.000 description 1
- HSOHROOUHRUSJR-UHFFFAOYSA-N n-[2-(5-methoxy-1h-indol-3-yl)ethyl]cyclopropanecarboxamide Chemical compound C12=CC(OC)=CC=C2NC=C1CCNC(=O)C1CC1 HSOHROOUHRUSJR-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005933 neopentyloxycarbonyl group Chemical group 0.000 description 1
- BMGNSKKZFQMGDH-FDGPNNRMSA-L nickel(2+);(z)-4-oxopent-2-en-2-olate Chemical compound [Ni+2].C\C([O-])=C\C(C)=O.C\C([O-])=C\C(C)=O BMGNSKKZFQMGDH-FDGPNNRMSA-L 0.000 description 1
- ZBRJXVVKPBZPAN-UHFFFAOYSA-L nickel(2+);triphenylphosphane;dichloride Chemical compound [Cl-].[Cl-].[Ni+2].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 ZBRJXVVKPBZPAN-UHFFFAOYSA-L 0.000 description 1
- 150000002826 nitrites Chemical class 0.000 description 1
- 125000001402 nonanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- 125000002801 octanoyl group Chemical group C(CCCCCCC)(=O)* 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- 125000005475 oxolanyl group Chemical group 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 125000003232 p-nitrobenzoyl group Chemical group [N+](=O)([O-])C1=CC=C(C(=O)*)C=C1 0.000 description 1
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 150000002941 palladium compounds Chemical class 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- QJPQVXSHYBGQGM-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 QJPQVXSHYBGQGM-UHFFFAOYSA-N 0.000 description 1
- 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000001148 pentyloxycarbonyl group Chemical group 0.000 description 1
- JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical class [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
- 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 239000001205 polyphosphate Substances 0.000 description 1
- 235000011176 polyphosphates Nutrition 0.000 description 1
- TZLVRPLSVNESQC-UHFFFAOYSA-N potassium azide Chemical compound [K+].[N-]=[N+]=[N-] TZLVRPLSVNESQC-UHFFFAOYSA-N 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003138 primary alcohols Chemical class 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000006233 propoxy propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])OC([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000006225 propoxyethyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- GRJJQCWNZGRKAU-UHFFFAOYSA-N pyridin-1-ium;fluoride Chemical compound F.C1=CC=NC=C1 GRJJQCWNZGRKAU-UHFFFAOYSA-N 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 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
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 238000011946 reduction process Methods 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 229910001925 ruthenium oxide Inorganic materials 0.000 description 1
- 238000010517 secondary reaction Methods 0.000 description 1
- 229940065287 selenium compound Drugs 0.000 description 1
- 150000003343 selenium compounds Chemical class 0.000 description 1
- RBBWNXJFTBCLKT-UHFFFAOYSA-M sodium;ethanethioate Chemical compound [Na+].CC([S-])=O RBBWNXJFTBCLKT-UHFFFAOYSA-M 0.000 description 1
- 125000003696 stearoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 235000011044 succinic acid Nutrition 0.000 description 1
- 229960005137 succinic acid Drugs 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003461 sulfonyl halides Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 108060008037 tachykinin Proteins 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- WDXXKETZCOFWQL-UHFFFAOYSA-N tert-butyl 1,2,2,2-tetrachloroethyl carbonate Chemical compound CC(C)(C)OC(=O)OC(Cl)C(Cl)(Cl)Cl WDXXKETZCOFWQL-UHFFFAOYSA-N 0.000 description 1
- QQWYQAQQADNEIC-RVDMUPIBSA-N tert-butyl [(z)-[cyano(phenyl)methylidene]amino] carbonate Chemical compound CC(C)(C)OC(=O)O\N=C(/C#N)C1=CC=CC=C1 QQWYQAQQADNEIC-RVDMUPIBSA-N 0.000 description 1
- IXZDIALLLMRYOU-UHFFFAOYSA-N tert-butyl hypochlorite Chemical compound CC(C)(C)OCl IXZDIALLLMRYOU-UHFFFAOYSA-N 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- VOVUARRWDCVURC-UHFFFAOYSA-N thiirane Chemical compound C1CS1 VOVUARRWDCVURC-UHFFFAOYSA-N 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 125000001166 thiolanyl group Chemical group 0.000 description 1
- 125000005505 thiomorpholino group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 208000004371 toothache Diseases 0.000 description 1
- 125000004784 trichloromethoxy group Chemical group ClC(O*)(Cl)Cl 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- STMPXDBGVJZCEX-UHFFFAOYSA-N triethylsilyl trifluoromethanesulfonate Chemical compound CC[Si](CC)(CC)OS(=O)(=O)C(F)(F)F STMPXDBGVJZCEX-UHFFFAOYSA-N 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
- 125000004951 trihalomethoxy group Chemical group 0.000 description 1
- SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- BYGOPQKDHGXNCD-UHFFFAOYSA-N tripotassium;iron(3+);hexacyanide Chemical compound [K+].[K+].[K+].[Fe+3].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-] BYGOPQKDHGXNCD-UHFFFAOYSA-N 0.000 description 1
- 125000000297 undecanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- GPPXJZIENCGNKB-UHFFFAOYSA-N vanadium Chemical compound [V]#[V] GPPXJZIENCGNKB-UHFFFAOYSA-N 0.000 description 1
- 208000018464 vernal keratoconjunctivitis Diseases 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
- CITILBVTAYEWKR-UHFFFAOYSA-L zinc trifluoromethanesulfonate Substances [Zn+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F CITILBVTAYEWKR-UHFFFAOYSA-L 0.000 description 1
- ZMLPZCGHASSGEA-UHFFFAOYSA-M zinc trifluoromethanesulfonate Chemical compound [Zn+2].[O-]S(=O)(=O)C(F)(F)F ZMLPZCGHASSGEA-UHFFFAOYSA-M 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/04—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/10—Spiro-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pulmonology (AREA)
- Physical Education & Sports Medicine (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Peptides Or Proteins (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP31382895 | 1995-12-01 | ||
JP33636995 | 1995-12-25 | ||
JP29686996 | 1996-11-08 |
Publications (2)
Publication Number | Publication Date |
---|---|
IL119729A0 IL119729A0 (en) | 1997-03-18 |
IL119729A true IL119729A (en) | 2001-07-24 |
Family
ID=27338095
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
IL11972996A IL119729A (en) | 1995-12-01 | 1996-12-01 | Heterocyclic compounds having tachykinin receptor antagonist activity and pharmaceutical compositions containing the same |
Country Status (19)
Country | Link |
---|---|
US (2) | US6159967A (fr) |
EP (1) | EP0776893B1 (fr) |
CN (1) | CN1142932C (fr) |
AT (1) | ATE213738T1 (fr) |
AU (1) | AU719158B2 (fr) |
CA (1) | CA2191815C (fr) |
CZ (1) | CZ288498B6 (fr) |
DE (1) | DE69619479T2 (fr) |
DK (1) | DK0776893T3 (fr) |
ES (1) | ES2170211T3 (fr) |
HK (1) | HK1011366A1 (fr) |
HU (1) | HU224225B1 (fr) |
IL (1) | IL119729A (fr) |
MX (1) | MX9606082A (fr) |
NO (1) | NO308300B1 (fr) |
NZ (1) | NZ299859A (fr) |
PT (1) | PT776893E (fr) |
RU (1) | RU2135494C1 (fr) |
TW (1) | TW367327B (fr) |
Families Citing this family (69)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
RU2135494C1 (ru) * | 1995-12-01 | 1999-08-27 | Санкио Компани Лимитед | Гетероциклические соединения и композиция на их основе, проявляющая антагонистическое действие в отношении рецепторов тахикинина |
AU732384B2 (en) | 1997-05-30 | 2001-04-26 | Sankyo Company Limited | Salts of an optically-active sulfoxide derivative |
HUP0004321A3 (en) | 1997-12-04 | 2002-04-29 | Sankyo Co | Alicyclic acylated heterocyclic derivatives and pharmaceutical compositions containing the same |
WO1999037642A1 (fr) | 1998-01-23 | 1999-07-29 | Sankyo Company, Limited | Derives de spiropiperidine |
WO2000034274A1 (fr) * | 1998-12-10 | 2000-06-15 | Sankyo Company, Limited | Derives de la cyclohexylpiperidine |
FR2791346B3 (fr) | 1999-03-25 | 2001-04-27 | Sanofi Sa | Nouveaux derives de morpholine, procede pour leur preparation et compositions pharmaceutiques les contenant |
FR2796069B3 (fr) * | 1999-07-09 | 2001-08-24 | Sanofi Synthelabo | Nouveaux procedes de preparation de derives de 2-(2- arylmorpholin-2-yl)ethanol substitues, enantiomeriquement purs, et composes intermediaires utiles dans ces procedes |
WO2001029027A1 (fr) * | 1999-10-22 | 2001-04-26 | Sankyo Company, Limited | Dérivés de 2-alcoxybenzène |
ES2304984T3 (es) | 1999-11-03 | 2008-11-01 | Amr Technology, Inc. | Tetra-hidroisoquinolinas de sustitucion arilica y heteroarilica y su utilizacion para bloquear la recaptacion de norepinefrina, dopamina y serotonina. |
US7163949B1 (en) | 1999-11-03 | 2007-01-16 | Amr Technology, Inc. | 4-phenyl substituted tetrahydroisoquinolines and use thereof |
CA2415532C (fr) | 2000-07-11 | 2010-05-11 | Albany Molecular Research, Inc. | Nouvelles tetrahydroisoquinolines 4-phenyl substituees et leur utilisation a des fins therapeutiques |
FR2824828B1 (fr) * | 2001-05-21 | 2005-05-20 | Sanofi Synthelabo | Nouveaux derives de piperidinecarboxamide, un procede pour leur preparation et les compositions pharmaceutiques les contenant |
WO2003104240A1 (fr) * | 2002-06-11 | 2003-12-18 | 三共株式会社 | Procede de production de thioether cyclique et de son intermediaire synthetique |
US7396930B2 (en) | 2002-06-11 | 2008-07-08 | Sankyo Company, Limited | Process for producing cyclic thioether and synthetic intermediate thereof |
JP2004067673A (ja) * | 2002-06-11 | 2004-03-04 | Sankyo Co Ltd | 環状チオエーテル類の製造法及びその合成中間体 |
MY141736A (en) * | 2002-10-08 | 2010-06-15 | Elanco Animal Health Ireland | Substituted 1,4-di-piperidin-4-yi-piperazine derivatives and their use as neurokinin antagonists |
WO2004037828A1 (fr) * | 2002-10-24 | 2004-05-06 | Sankyo Company, Limited | Procede de production de sulfoxyde optiquement actif |
WO2005080339A1 (fr) * | 2004-02-25 | 2005-09-01 | Sankyo Company, Limited | Dérivés du sulfonyloxy |
AU2005214274A1 (en) | 2004-02-25 | 2005-09-01 | Sankyo Company, Limited | Indanol derivative |
JP5007226B2 (ja) | 2004-07-15 | 2012-08-22 | エーエムアール テクノロジー インコーポレイテッド | アリールおよびヘテロアリール置換テトラヒドロイソキノリンならびにノルエピネフリン、ドーパミン、およびセロトニンの再取り込みを遮断するためのその利用方法 |
FR2873373B1 (fr) * | 2004-07-23 | 2006-09-08 | Sanofi Synthelabo | Derives de 4-arylmorpholin-3-one, leur preparation et leur application en therapeutique |
JP2008510728A (ja) * | 2004-08-19 | 2008-04-10 | バーテックス ファーマシューティカルズ インコーポレイテッド | ムスカリン受容体のモジュレーター |
WO2006123182A2 (fr) | 2005-05-17 | 2006-11-23 | Merck Sharp & Dohme Limited | Sulfones de cyclohexyle pour le traitement du cancer |
KR101589551B1 (ko) | 2005-07-15 | 2016-02-02 | 알바니 몰레큘라 리써치, 인크. | 아릴- 및 헤테로아릴-치환된 테트라히드로벤자제핀, 및 노르에피네프린, 도파민 및 세로토닌의 재흡수를 차단하기 위한 용도 |
EP2314295B1 (fr) | 2005-07-29 | 2015-01-28 | Resverlogix, Inc | Compositions pharmaceutiques pour la prevention et le traitement de maladies complexes et leur administration par des dispositifs medicaux inserables |
GB0603041D0 (en) | 2006-02-15 | 2006-03-29 | Angeletti P Ist Richerche Bio | Therapeutic compounds |
US20110218176A1 (en) | 2006-11-01 | 2011-09-08 | Barbara Brooke Jennings-Spring | Compounds, methods, and treatments for abnormal signaling pathways for prenatal and postnatal development |
CN101190330A (zh) | 2006-11-30 | 2008-06-04 | 深圳市鼎兴生物医药技术开发有限公司 | 胆碱酯酶在拮抗速激肽药物中的应用 |
EP2109608B1 (fr) | 2007-01-10 | 2011-03-23 | Istituto di Richerche di Biologia Molecolare P. Angeletti S.p.A. | Indazoles à substitution amide utilisés comme inhibiteurs de la poly(adp-ribose)polymérase (parp) |
WO2008094663A2 (fr) * | 2007-01-31 | 2008-08-07 | Adam Heller | Gestion de la douleur par voie électrochimique |
MX2009008099A (es) | 2007-02-01 | 2009-12-14 | Resverlogix Corp | Compuestos para la prevencion y tratamiento de enfermedades cardiovasculares. |
EP3103791B1 (fr) | 2007-06-27 | 2018-01-31 | Merck Sharp & Dohme Corp. | Dérivés de 4-carboxybenzylamino utilisés comme inhibiteurs de l'histone désacétylase |
AR071997A1 (es) | 2008-06-04 | 2010-07-28 | Bristol Myers Squibb Co | Forma cristalina de 6-((4s)-2-metil-4-(2-naftil)-1,2,3,4-tetrahidroisoquinolin-7-il)piridazin-3-amina |
US9156812B2 (en) | 2008-06-04 | 2015-10-13 | Bristol-Myers Squibb Company | Crystalline form of 6-[(4S)-2-methyl-4-(2-naphthyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]pyridazin-3-amine |
KR101629356B1 (ko) | 2008-06-26 | 2016-06-13 | 리스버로직스 코퍼레이션 | 퀴나졸리논 유도체의 제조방법 |
CA2747417C (fr) | 2009-01-08 | 2017-01-03 | Resverlogix Corp. | Composes pour la prevention et le traitement de maladies cardiovasculaires |
US9238640B2 (en) | 2009-03-18 | 2016-01-19 | Resverlogix Corp. | Anti-inflammatory agents |
WO2010114780A1 (fr) | 2009-04-01 | 2010-10-07 | Merck Sharp & Dohme Corp. | Inhibiteurs de l'activité akt |
BRPI1014956B8 (pt) | 2009-04-22 | 2021-05-25 | Resverlogix Corp | agentes anti-inflamatórios |
KR101830447B1 (ko) | 2009-05-12 | 2018-02-20 | 알바니 몰레큘라 리써치, 인크. | 7-([1,2,4]트리아졸로[1,5-α]피리딘-6-일)-4-(3,4-디클로로페닐)-1,2,3,4-테트라하이드로이소퀴놀린 및 이의 용도 |
JP5739415B2 (ja) | 2009-05-12 | 2015-06-24 | ブリストル−マイヤーズ スクウィブ カンパニー | (S)−7−([1,2,4]トリアゾロ[1,5−a]ピリジン−6−イル)−4−(3,4−ジクロロフェニル)−1,2,3,4−テトラヒドロイソキノリンの結晶形態およびその使用 |
CN102458123A (zh) | 2009-05-12 | 2012-05-16 | 阿尔巴尼分子研究公司 | 芳基、杂芳基和杂环取代的四氢异喹啉及其用途 |
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JP6043285B2 (ja) | 2010-08-02 | 2016-12-14 | サーナ・セラピューティクス・インコーポレイテッドSirna Therapeutics,Inc. | 低分子干渉核酸(siNA)を用いたカテニン(カドヘリン結合型タンパク質)β1(CTNNB1)遺伝子発現のRNA干渉媒介性阻害 |
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EP2608669B1 (fr) | 2010-08-23 | 2016-06-22 | Merck Sharp & Dohme Corp. | Nouveaux dérivés de pyrazolo[1,5-a]pyrimidine utilisés comme inhibiteurs de mtor |
EP2613782B1 (fr) | 2010-09-01 | 2016-11-02 | Merck Sharp & Dohme Corp. | Dérivés d'indazole utilisables en tant qu'inhibiteurs de la voie erk |
US9242981B2 (en) | 2010-09-16 | 2016-01-26 | Merck Sharp & Dohme Corp. | Fused pyrazole derivatives as novel ERK inhibitors |
ES2663009T3 (es) | 2010-10-29 | 2018-04-10 | Sirna Therapeutics, Inc. | Inhibición de la expresión génica mediada por interferencia por ARN utilizando ácidos nucleicos de interferencia cortos (ANic) |
EP2654748B1 (fr) | 2010-12-21 | 2016-07-27 | Merck Sharp & Dohme Corp. | Dérivés d'indazole utiles en tant qu'inhibiteurs de erk |
CN103732592A (zh) | 2011-04-21 | 2014-04-16 | 默沙东公司 | ***-1受体抑制剂 |
WO2013063214A1 (fr) | 2011-10-27 | 2013-05-02 | Merck Sharp & Dohme Corp. | Nouveaux composés qui sont des inhibiteurs d'erk |
JP5992049B2 (ja) | 2011-11-01 | 2016-09-14 | レスバーロジックス コーポレイション | 置換されたキナゾリノンのための経口速放性製剤 |
EP3358013B1 (fr) | 2012-05-02 | 2020-06-24 | Sirna Therapeutics, Inc. | Compositions d'acide nucléique interférent court (sina) |
BR102012024778A2 (pt) * | 2012-09-28 | 2014-08-19 | Cristalia Prod Quimicos Farm | Compostos heteroaromáticos; processo para preparar os compostos, composições farmacêuticas, usos e método de tratamento para as dores aguda e crônica |
CN105050598B (zh) | 2012-09-28 | 2018-04-27 | 默沙东公司 | 作为erk抑制剂的新型化合物 |
WO2014080291A2 (fr) | 2012-11-21 | 2014-05-30 | Rvx Therapeutics Inc. | Dérivés biaryle servant d'inhibiteurs de bromodomaines |
WO2014080290A2 (fr) | 2012-11-21 | 2014-05-30 | Rvx Therapeutics Inc. | Amines cycliques servant d'inhibiteurs de bromodomaines |
CA2892361A1 (fr) | 2012-11-28 | 2014-06-05 | Merck Sharp & Dohme Corp. | Utilisation d'un inhibiteur wee1 pour traiter un cancer caracterise par de faibles niveaux d'expression de proteines tyrosine et threonine kinases 1 (pkmyt1) associee a la membrane |
AU2013361694B2 (en) | 2012-12-20 | 2017-10-26 | Merck Sharp & Dohme Corp. | Substituted imidazopyridines as HDM2 inhibitors |
WO2014096965A2 (fr) | 2012-12-21 | 2014-06-26 | Rvx Therapeutics Inc. | Nouveaux composés hétérocycliques en tant qu'inhibiteurs de bromodomaine |
WO2014120748A1 (fr) | 2013-01-30 | 2014-08-07 | Merck Sharp & Dohme Corp. | Purines 2,6,7,8-substituées utilisées en tant qu'inhibiteurs de hdm2 |
EP3041938A1 (fr) | 2013-09-03 | 2016-07-13 | Moderna Therapeutics, Inc. | Polynucléotides circulaires |
JP6903585B2 (ja) | 2015-03-13 | 2021-07-14 | レスバーロジックス コーポレイション | 補体関連疾患の治療のための組成物および治療方法 |
EP3525785A4 (fr) | 2016-10-12 | 2020-03-25 | Merck Sharp & Dohme Corp. | Inhibiteurs de kdm5 |
WO2019094311A1 (fr) | 2017-11-08 | 2019-05-16 | Merck Sharp & Dohme Corp. | Inhibiteurs de prmt5 |
WO2020033282A1 (fr) | 2018-08-07 | 2020-02-13 | Merck Sharp & Dohme Corp. | Inhibiteurs de prmt5 |
US11981701B2 (en) | 2018-08-07 | 2024-05-14 | Merck Sharp & Dohme Llc | PRMT5 inhibitors |
WO2020101017A1 (fr) * | 2018-11-15 | 2020-05-22 | 国立大学法人九州大学 | Agent prophylactique ou thérapeutique et composition médicinale contre une maladie à médiation par l'il-31 |
Family Cites Families (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FI97540C (fi) * | 1989-11-06 | 1997-01-10 | Sanofi Sa | Menetelmä terapeuttisesti käyttökelpoisten, aromaattisesti substituoitujen piperidiini- ja piperatsiinijohdannaisten valmistamiseksi |
IL99320A (en) * | 1990-09-05 | 1995-07-31 | Sanofi Sa | Arylalkylamines, their preparation and pharmaceutical preparations containing them |
FR2676054B1 (fr) * | 1991-05-03 | 1993-09-03 | Sanofi Elf | Nouveaux composes n-alkylenepiperidino et leurs enantiomeres, procede pour leur preparation et compositions pharmaceutiques les contenant. |
FR2676055B1 (fr) * | 1991-05-03 | 1993-09-03 | Sanofi Elf | Composes polycycliques amines et leurs enantiomeres, procede pour leur preparation et compositions pharmaceutiques les contenant. |
GB9125515D0 (en) * | 1991-11-29 | 1992-01-29 | Merck Sharp & Dohme | Therapeutic agents |
ES2087567T3 (es) | 1991-12-18 | 1996-07-16 | Lepetit Spa | Derivados antibioticos de 7'-amino-naftazarina. |
ES2119174T3 (es) * | 1993-01-28 | 1998-10-01 | Merck & Co Inc | Azaciclos espiro-sustituidos como antagonistas de los receptores de las taquiquininas. |
EP0696280B1 (fr) | 1993-05-06 | 1997-09-24 | Merrell Pharmaceuticals Inc. | Pyrrolidin-3-yl-alkyl-piperidines substituees utiles comme antagonistes de la tachykinine |
GB9310713D0 (en) * | 1993-05-24 | 1993-07-07 | Zeneca Ltd | Aryl substituted heterocycles |
AU680020B2 (en) * | 1993-06-07 | 1997-07-17 | Merck & Co., Inc. | Spiro-substituted azacycles as neurokinin antagonists |
FR2719311B1 (fr) * | 1994-03-18 | 1998-06-26 | Sanofi Sa | Composés antagonistes sélectifs du récepteur NK3 humain et leur utilisation comme médicaments et outils de diagnostic. |
WO1995028389A1 (fr) * | 1994-04-15 | 1995-10-26 | Yamanouchi Pharmaceutical Co., Ltd. | Compose spiro et composition medicinale issue de ce compose |
FR2729954B1 (fr) * | 1995-01-30 | 1997-08-01 | Sanofi Sa | Composes heterocycliques substitues, procede pour leur preparation et compositions pharmaceutiques les contenant |
FR2729952B1 (fr) | 1995-01-30 | 1997-04-18 | Sanofi Sa | Composes heterocycliques substitues, procede pour leur preparation et compositions pharmaceutiques les contenant |
FR2729951B1 (fr) * | 1995-01-30 | 1997-04-18 | Sanofi Sa | Nouveaux composes heterocycliques, procede pour leur preparation et compositions pharmaceutiques en contenant |
RU2135494C1 (ru) * | 1995-12-01 | 1999-08-27 | Санкио Компани Лимитед | Гетероциклические соединения и композиция на их основе, проявляющая антагонистическое действие в отношении рецепторов тахикинина |
JP3192631B2 (ja) * | 1997-05-28 | 2001-07-30 | 三共株式会社 | 飽和複素環化合物からなる医薬 |
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1996
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- 1996-11-29 HU HU9603298A patent/HU224225B1/hu not_active IP Right Cessation
- 1996-11-30 TW TW085114815A patent/TW367327B/zh not_active IP Right Cessation
- 1996-12-01 IL IL11972996A patent/IL119729A/en not_active IP Right Cessation
- 1996-12-01 CN CNB961238887A patent/CN1142932C/zh not_active Expired - Fee Related
- 1996-12-02 AT AT96308711T patent/ATE213738T1/de not_active IP Right Cessation
- 1996-12-02 DE DE69619479T patent/DE69619479T2/de not_active Expired - Lifetime
- 1996-12-02 NZ NZ299859A patent/NZ299859A/xx unknown
- 1996-12-02 AU AU74065/96A patent/AU719158B2/en not_active Ceased
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- 1996-12-02 DK DK96308711T patent/DK0776893T3/da active
- 1996-12-02 PT PT96308711T patent/PT776893E/pt unknown
- 1996-12-02 EP EP96308711A patent/EP0776893B1/fr not_active Expired - Lifetime
- 1996-12-02 CZ CZ19963521A patent/CZ288498B6/cs not_active IP Right Cessation
- 1996-12-02 CA CA002191815A patent/CA2191815C/fr not_active Expired - Fee Related
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Also Published As
Publication number | Publication date |
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ATE213738T1 (de) | 2002-03-15 |
HU224225B1 (hu) | 2005-06-28 |
DK0776893T3 (da) | 2002-03-18 |
DE69619479T2 (de) | 2002-10-17 |
HK1011366A1 (en) | 1999-07-09 |
CZ352196A3 (en) | 1997-06-11 |
CN1142932C (zh) | 2004-03-24 |
CZ288498B6 (en) | 2001-06-13 |
NO965125D0 (no) | 1996-12-02 |
AU719158B2 (en) | 2000-05-04 |
MX9606082A (es) | 1998-08-30 |
HU9603298D0 (en) | 1997-01-28 |
EP0776893B1 (fr) | 2002-02-27 |
DE69619479D1 (de) | 2002-04-04 |
TW367327B (en) | 1999-08-21 |
US6448247B1 (en) | 2002-09-10 |
CN1157286A (zh) | 1997-08-20 |
NZ299859A (en) | 1997-11-24 |
ES2170211T3 (es) | 2002-08-01 |
AU7406596A (en) | 1997-06-05 |
HUP9603298A3 (en) | 1999-10-28 |
PT776893E (pt) | 2002-06-28 |
IL119729A0 (en) | 1997-03-18 |
US6159967A (en) | 2000-12-12 |
NO965125L (no) | 1997-06-02 |
RU2135494C1 (ru) | 1999-08-27 |
CA2191815A1 (fr) | 1997-06-02 |
CA2191815C (fr) | 2005-05-10 |
EP0776893A1 (fr) | 1997-06-04 |
NO308300B1 (no) | 2000-08-28 |
HUP9603298A2 (hu) | 1998-09-28 |
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