NO830643L - Fremgangsmaate for fremstilling av heterocykliske derivater som virker paa histaminreseptorer - Google Patents
Fremgangsmaate for fremstilling av heterocykliske derivater som virker paa histaminreseptorerInfo
- Publication number
- NO830643L NO830643L NO830643A NO830643A NO830643L NO 830643 L NO830643 L NO 830643L NO 830643 A NO830643 A NO 830643A NO 830643 A NO830643 A NO 830643A NO 830643 L NO830643 L NO 830643L
- Authority
- NO
- Norway
- Prior art keywords
- group
- alkyl
- methyl
- substituted
- oxygen
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 28
- 238000002360 preparation method Methods 0.000 title claims description 23
- 102000000543 Histamine Receptors Human genes 0.000 title description 3
- 108010002059 Histamine Receptors Proteins 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 107
- 125000000217 alkyl group Chemical group 0.000 claims description 81
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 65
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 53
- 229910052760 oxygen Inorganic materials 0.000 claims description 53
- 239000001301 oxygen Substances 0.000 claims description 53
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 44
- -1 -NH- Chemical group 0.000 claims description 43
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 37
- 229910052739 hydrogen Inorganic materials 0.000 claims description 35
- 239000001257 hydrogen Substances 0.000 claims description 35
- 229910052717 sulfur Chemical group 0.000 claims description 34
- 239000011593 sulfur Chemical group 0.000 claims description 33
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 32
- 125000003545 alkoxy group Chemical group 0.000 claims description 30
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 28
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 23
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 23
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 23
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 22
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 19
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 18
- 125000001072 heteroaryl group Chemical group 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 17
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 16
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 15
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 14
- 229910021529 ammonia Inorganic materials 0.000 claims description 14
- 125000004423 acyloxy group Chemical group 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 125000002252 acyl group Chemical group 0.000 claims description 12
- 238000007363 ring formation reaction Methods 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 10
- 125000003342 alkenyl group Chemical group 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 150000001412 amines Chemical class 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 125000002541 furyl group Chemical group 0.000 claims description 7
- 125000005842 heteroatom Chemical group 0.000 claims description 7
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 150000004677 hydrates Chemical class 0.000 claims description 5
- 150000002576 ketones Chemical class 0.000 claims description 5
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 5
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 5
- 239000005864 Sulphur Substances 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
- 125000004122 cyclic group Chemical group 0.000 claims description 4
- 125000004990 dihydroxyalkyl group Chemical group 0.000 claims description 4
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 3
- 150000001450 anions Chemical class 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 3
- HPJBZDAQYZOORB-UHFFFAOYSA-N 2-methyl-5-[(1-methyltetrazol-5-yl)sulfanylmethyl]-n-[3-[3-(piperidin-1-ylmethyl)phenoxy]propyl]-1,2,4-triazol-3-amine Chemical compound CN1N=NN=C1SCC1=NN(C)C(NCCCOC=2C=C(CN3CCCCC3)C=CC=2)=N1 HPJBZDAQYZOORB-UHFFFAOYSA-N 0.000 claims description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 2
- 239000007818 Grignard reagent Substances 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
- 150000004795 grignard reagents Chemical class 0.000 claims description 2
- 150000002366 halogen compounds Chemical class 0.000 claims description 2
- 230000002140 halogenating effect Effects 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 150000002900 organolithium compounds Chemical class 0.000 claims description 2
- 150000003852 triazoles Chemical class 0.000 claims description 2
- 125000004950 trifluoroalkyl group Chemical group 0.000 claims description 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 2
- NHXVMUPJDJEBCI-UHFFFAOYSA-N [1-methyl-5-[3-[3-(piperidin-1-ylmethyl)phenoxy]propylamino]-1,2,4-triazol-3-yl]-pyridin-2-ylmethanol Chemical compound CN1N=C(C(O)C=2N=CC=CC=2)N=C1NCCCOC(C=1)=CC=CC=1CN1CCCCC1 NHXVMUPJDJEBCI-UHFFFAOYSA-N 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 111
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 63
- 239000000243 solution Substances 0.000 description 44
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 31
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 27
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 24
- 239000000203 mixture Substances 0.000 description 22
- 239000007787 solid Substances 0.000 description 22
- 239000000284 extract Substances 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
- 239000002904 solvent Substances 0.000 description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 239000003480 eluent Substances 0.000 description 15
- 229910000029 sodium carbonate Inorganic materials 0.000 description 15
- 229910000027 potassium carbonate Inorganic materials 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 13
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 238000004809 thin layer chromatography Methods 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 230000002378 acidificating effect Effects 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 239000000543 intermediate Substances 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- 229940126062 Compound A Drugs 0.000 description 8
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 239000000843 powder Substances 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 6
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 6
- HAMNKKUPIHEESI-UHFFFAOYSA-N aminoguanidine Chemical compound NNC(N)=N HAMNKKUPIHEESI-UHFFFAOYSA-N 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 239000006260 foam Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 4
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 4
- 150000008065 acid anhydrides Chemical class 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 150000001299 aldehydes Chemical class 0.000 description 4
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 4
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 229960004592 isopropanol Drugs 0.000 description 4
- VTLNPNNUIJHJQB-UHFFFAOYSA-N loxtidine Chemical compound CN1N=C(CO)N=C1NCCCOC1=CC=CC(CN2CCCCC2)=C1 VTLNPNNUIJHJQB-UHFFFAOYSA-N 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 125000002950 monocyclic group Chemical group 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910052727 yttrium Inorganic materials 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- NXAHSGCCZWGLTG-UHFFFAOYSA-N [4-methyl-5-[3-[3-(piperidin-1-ylmethyl)phenoxy]propylamino]-1,2,4-triazol-3-yl]-phenylmethanol Chemical compound N=1N=C(C(O)C=2C=CC=CC=2)N(C)C=1NCCCOC(C=1)=CC=CC=1CN1CCCCC1 NXAHSGCCZWGLTG-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 239000002775 capsule Substances 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
- 150000004985 diamines Chemical class 0.000 description 3
- 239000002024 ethyl acetate extract Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 150000004820 halides Chemical class 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 229960001340 histamine Drugs 0.000 description 3
- 150000002905 orthoesters Chemical class 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 230000002335 preservative effect Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 125000004076 pyridyl group Chemical group 0.000 description 3
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 3
- 125000001544 thienyl group Chemical group 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- JFGCGQJHMUYGLU-UHFFFAOYSA-N 2-[[5-[(dimethylamino)methyl]furan-2-yl]methylsulfanyl]ethanamine Chemical compound CN(C)CC1=CC=C(CSCCN)O1 JFGCGQJHMUYGLU-UHFFFAOYSA-N 0.000 description 2
- VQSXCZMVUMSITD-UHFFFAOYSA-N 3-[3-(piperidin-1-ylmethyl)phenoxy]propan-1-amine Chemical compound NCCCOC1=CC=CC(CN2CCCCC2)=C1 VQSXCZMVUMSITD-UHFFFAOYSA-N 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 241000400611 Eucalyptus deanei Species 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- JLXINTYODRHROP-UHFFFAOYSA-N [2-acetyloxy-3-[[[(benzylideneamino)-methylamino]-methylsulfanylmethylidene]amino]-3-oxopropyl] acetate Chemical compound CC(=O)OCC(OC(C)=O)C(=O)N=C(SC)N(C)N=CC1=CC=CC=C1 JLXINTYODRHROP-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 125000005907 alkyl ester group Chemical group 0.000 description 2
- 230000000172 allergic effect Effects 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- WERYXYBDKMZEQL-UHFFFAOYSA-N butane-1,4-diol Chemical compound OCCCCO WERYXYBDKMZEQL-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 150000001805 chlorine compounds Chemical class 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- DDRPCXLAQZKBJP-UHFFFAOYSA-N furfurylamine Chemical compound NCC1=CC=CO1 DDRPCXLAQZKBJP-UHFFFAOYSA-N 0.000 description 2
- 210000004051 gastric juice Anatomy 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 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 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 238000003419 tautomerization reaction Methods 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- OTSZMWCSGBDNQQ-UHFFFAOYSA-N 1-amino-3-[3-(piperidin-1-ylmethyl)phenoxy]propan-2-ol Chemical compound NCC(O)COC1=CC=CC(CN2CCCCC2)=C1 OTSZMWCSGBDNQQ-UHFFFAOYSA-N 0.000 description 1
- XOHZHMUQBFJTNH-UHFFFAOYSA-N 1-methyl-2h-tetrazole-5-thione Chemical compound CN1N=NN=C1S XOHZHMUQBFJTNH-UHFFFAOYSA-N 0.000 description 1
- ACFTYQVNSIGREH-UHFFFAOYSA-N 1-methyl-5-[3-[3-(piperidin-1-ylmethyl)phenoxy]propylamino]-1,2,4-triazole-3-carbaldehyde Chemical compound CN1N=C(C=O)N=C1NCCCOC1=CC=CC(CN2CCCCC2)=C1 ACFTYQVNSIGREH-UHFFFAOYSA-N 0.000 description 1
- LYUPJHVGLFETDG-UHFFFAOYSA-N 1-phenylbutan-2-ol Chemical compound CCC(O)CC1=CC=CC=C1 LYUPJHVGLFETDG-UHFFFAOYSA-N 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 1
- DUILGEYLVHGSEE-UHFFFAOYSA-N 2-(oxiran-2-ylmethyl)isoindole-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1CC1CO1 DUILGEYLVHGSEE-UHFFFAOYSA-N 0.000 description 1
- ZFFTZDQKIXPDAF-UHFFFAOYSA-N 2-Furanmethanethiol Chemical compound SCC1=CC=CO1 ZFFTZDQKIXPDAF-UHFFFAOYSA-N 0.000 description 1
- SNUYATJCUINXPQ-UHFFFAOYSA-N 2-[2-[3-(piperidin-1-ylmethyl)phenoxy]ethoxy]ethanamine Chemical compound NCCOCCOC1=CC=CC(CN2CCCCC2)=C1 SNUYATJCUINXPQ-UHFFFAOYSA-N 0.000 description 1
- IMRWILPUOVGIMU-UHFFFAOYSA-N 2-bromopyridine Chemical compound BrC1=CC=CC=N1 IMRWILPUOVGIMU-UHFFFAOYSA-N 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- ZMXYYGHPWHYHDN-UHFFFAOYSA-N 2-methyl-5-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanylmethyl]-n-[3-[3-(piperidin-1-ylmethyl)phenoxy]propyl]-1,2,4-triazol-3-amine Chemical compound S1C(C)=NN=C1SCC1=NN(C)C(NCCCOC=2C=C(CN3CCCCC3)C=CC=2)=N1 ZMXYYGHPWHYHDN-UHFFFAOYSA-N 0.000 description 1
- SPKBWUZSWDZBCD-UHFFFAOYSA-N 2-methyl-n-[3-[3-(piperidin-1-ylmethyl)phenoxy]propyl]-5-(prop-2-enoxymethyl)-1,2,4-triazol-3-amine Chemical compound CN1N=C(COCC=C)N=C1NCCCOC1=CC=CC(CN2CCCCC2)=C1 SPKBWUZSWDZBCD-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- ORGBERFQYFWYGX-UHFFFAOYSA-N 3-(piperidin-1-ylmethyl)phenol Chemical compound OC1=CC=CC(CN2CCCCC2)=C1 ORGBERFQYFWYGX-UHFFFAOYSA-N 0.000 description 1
- DSJSKLRBUNEIAX-UHFFFAOYSA-N 3-[3-(1,3-dioxolan-2-yl)phenoxy]propan-1-amine Chemical compound NCCCOC1=CC=CC(C2OCCO2)=C1 DSJSKLRBUNEIAX-UHFFFAOYSA-N 0.000 description 1
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
- FPVUWZFFEGYCGB-UHFFFAOYSA-N 5-methyl-3h-1,3,4-thiadiazole-2-thione Chemical compound CC1=NN=C(S)S1 FPVUWZFFEGYCGB-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- DWZRSDQJFASYIF-UHFFFAOYSA-N [2-[[[(benzylideneamino)-methylamino]-methylsulfanylmethylidene]amino]-2-oxo-1-phenylethyl] acetate Chemical compound C=1C=CC=CC=1C=NN(C)C(SC)=NC(=O)C(OC(C)=O)C1=CC=CC=C1 DWZRSDQJFASYIF-UHFFFAOYSA-N 0.000 description 1
- RFQQVCKCNYOJEU-UHFFFAOYSA-N [2-[methyl-(1-phenylethylideneamino)amino]-2-oxo-1-phenylethyl] acetate Chemical compound CC(=NN(C)C(C(C1=CC=CC=C1)OC(C)=O)=O)C1=CC=CC=C1 RFQQVCKCNYOJEU-UHFFFAOYSA-N 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- ORWKVZNEPHTCQE-UHFFFAOYSA-N acetic formic anhydride Chemical compound CC(=O)OC=O ORWKVZNEPHTCQE-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000000278 alkyl amino alkyl group Chemical group 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 125000004103 aminoalkyl group Chemical group 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 125000003435 aroyl group Chemical group 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- 239000003637 basic solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000012455 biphasic mixture Substances 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 description 1
- FSBVERYRVPGNGG-UHFFFAOYSA-N dimagnesium dioxido-bis[[oxido(oxo)silyl]oxy]silane hydrate Chemical class O.[Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O FSBVERYRVPGNGG-UHFFFAOYSA-N 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- TYUFVPKAYCKUID-UHFFFAOYSA-N ethyl 2-[[1-methyl-5-[3-[3-(piperidin-1-ylmethyl)phenoxy]propylamino]-1,2,4-triazol-3-yl]methylsulfanyl]acetate Chemical compound CN1N=C(CSCC(=O)OCC)N=C1NCCCOC1=CC=CC(CN2CCCCC2)=C1 TYUFVPKAYCKUID-UHFFFAOYSA-N 0.000 description 1
- UAYKGOMDUQLCJS-UHFFFAOYSA-N ethylsulfanyl acetate Chemical compound CCSOC(C)=O UAYKGOMDUQLCJS-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 210000002837 heart atrium Anatomy 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000012943 hotmelt Substances 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 150000002464 imidothioesters Chemical class 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
- 229940011051 isopropyl acetate Drugs 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000005905 mesyloxy group Chemical group 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- IXEGSTUUYSHYCN-UHFFFAOYSA-N n-(benzylideneamino)-n-methylmethanamine Chemical compound CN(C)N=CC1=CC=CC=C1 IXEGSTUUYSHYCN-UHFFFAOYSA-N 0.000 description 1
- HOXWDQYXKMMSLI-UHFFFAOYSA-N n-methyl-2-[[1-methyl-5-[3-[3-(piperidin-1-ylmethyl)phenoxy]propylamino]-1,2,4-triazol-3-yl]methylsulfanyl]acetamide Chemical compound CN1N=C(CSCC(=O)NC)N=C1NCCCOC1=CC=CC(CN2CCCCC2)=C1 HOXWDQYXKMMSLI-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 125000003884 phenylalkyl group Chemical group 0.000 description 1
- 125000005543 phthalimide group Chemical group 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000004237 preparative chromatography Methods 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
- C07D249/14—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8205431 | 1982-02-24 | ||
| GB8205723 | 1982-02-26 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO830643L true NO830643L (no) | 1983-08-25 |
Family
ID=26282061
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO830643A NO830643L (no) | 1982-02-24 | 1983-02-24 | Fremgangsmaate for fremstilling av heterocykliske derivater som virker paa histaminreseptorer |
Country Status (18)
| Country | Link |
|---|---|
| JP (1) | JPS58157772A (sv) |
| AU (1) | AU1180383A (sv) |
| BE (1) | BE896012A (sv) |
| DE (1) | DE3306503A1 (sv) |
| DK (1) | DK88283A (sv) |
| ES (2) | ES520031A0 (sv) |
| FI (1) | FI830609L (sv) |
| FR (1) | FR2521993B1 (sv) |
| GB (1) | GB2116178B (sv) |
| GR (1) | GR77048B (sv) |
| IL (1) | IL67990A0 (sv) |
| IT (1) | IT1167622B (sv) |
| LU (1) | LU84659A1 (sv) |
| NL (1) | NL8300697A (sv) |
| NO (1) | NO830643L (sv) |
| NZ (1) | NZ203384A (sv) |
| PT (1) | PT76280A (sv) |
| SE (1) | SE8301039L (sv) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3336410A1 (de) * | 1983-10-06 | 1985-04-18 | Ludwig Heumann & Co GmbH, 8500 Nürnberg | Sulfenamidderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| FR2815346B1 (fr) * | 2000-10-13 | 2004-02-20 | Servier Lab | Nouveaux composes aminotriazolones, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK89480A (da) * | 1979-03-02 | 1980-09-03 | Glaxo Group Ltd | R fremgangsmaade til fremstilling af heterocycliske forbindelse |
| EP0029303B1 (en) * | 1979-10-22 | 1985-01-30 | Glaxo Group Limited | 1,2,4-triazole derivatives, processes for their production and pharmaceutical compositions containing them |
| AU538818B2 (en) * | 1979-10-22 | 1984-08-30 | Glaxo Group Limited | 1-h-1,2,4-triazole compounds |
| DE3068712D1 (en) * | 1979-10-23 | 1984-08-30 | Glaxo Group Ltd | Aminoalkyl compounds, their production and pharmaceutical compositions containing them |
| CH655104A5 (fr) * | 1980-02-28 | 1986-03-27 | Glaxo Group Ltd | Derives heterocycliques triazoliques, procedes pour leur preparation et compositions pharmaceutiques les comportant. |
-
1983
- 1983-02-23 PT PT76280A patent/PT76280A/pt unknown
- 1983-02-23 ES ES520031A patent/ES520031A0/es active Granted
- 1983-02-24 LU LU84659A patent/LU84659A1/fr unknown
- 1983-02-24 GB GB08305147A patent/GB2116178B/en not_active Expired
- 1983-02-24 NO NO830643A patent/NO830643L/no unknown
- 1983-02-24 AU AU11803/83A patent/AU1180383A/en not_active Abandoned
- 1983-02-24 NL NL8300697A patent/NL8300697A/nl not_active Application Discontinuation
- 1983-02-24 BE BE0/210201A patent/BE896012A/fr not_active IP Right Cessation
- 1983-02-24 JP JP58030160A patent/JPS58157772A/ja active Pending
- 1983-02-24 FR FR8303011A patent/FR2521993B1/fr not_active Expired
- 1983-02-24 NZ NZ203384A patent/NZ203384A/en unknown
- 1983-02-24 DK DK88283A patent/DK88283A/da not_active Application Discontinuation
- 1983-02-24 FI FI830609A patent/FI830609L/fi not_active Application Discontinuation
- 1983-02-24 DE DE19833306503 patent/DE3306503A1/de not_active Withdrawn
- 1983-02-24 IT IT47786/83A patent/IT1167622B/it active
- 1983-02-24 SE SE8301039A patent/SE8301039L/sv not_active Application Discontinuation
- 1983-02-24 IL IL67990A patent/IL67990A0/xx unknown
- 1983-02-24 GR GR70604A patent/GR77048B/el unknown
- 1983-10-17 ES ES526532A patent/ES526532A0/es active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| BE896012A (fr) | 1983-08-24 |
| SE8301039L (sv) | 1983-08-25 |
| DK88283A (da) | 1983-08-25 |
| IT8347786A0 (it) | 1983-02-24 |
| GB2116178B (en) | 1985-10-02 |
| DK88283D0 (da) | 1983-02-24 |
| ES8602702A1 (es) | 1985-11-16 |
| IL67990A0 (en) | 1983-06-15 |
| ES526532A0 (es) | 1985-11-16 |
| LU84659A1 (fr) | 1984-11-08 |
| FI830609L (fi) | 1983-08-25 |
| JPS58157772A (ja) | 1983-09-19 |
| GB8305147D0 (en) | 1983-03-30 |
| NL8300697A (nl) | 1983-09-16 |
| GR77048B (sv) | 1984-09-04 |
| ES8407030A1 (es) | 1984-04-01 |
| IT1167622B (it) | 1987-05-13 |
| ES520031A0 (es) | 1984-04-01 |
| FR2521993A1 (fr) | 1983-08-26 |
| GB2116178A (en) | 1983-09-21 |
| NZ203384A (en) | 1985-08-16 |
| FI830609A0 (fi) | 1983-02-24 |
| PT76280A (en) | 1983-03-01 |
| DE3306503A1 (de) | 1983-09-01 |
| FR2521993B1 (fr) | 1988-09-16 |
| SE8301039D0 (sv) | 1983-02-24 |
| AU1180383A (en) | 1983-09-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0839144B1 (en) | Piperazine derivatives as therapeutic agents | |
| AU771273B2 (en) | Compounds useful as anti-inflammatory agents | |
| US4524071A (en) | Pyrimidone derivatives | |
| JPH02218661A (ja) | 改良されたセロトニンおよびノルエピネフリン取り込み阻害剤 | |
| RU2382766C2 (ru) | Производные арилсульфонилстильбена для лечения бессонницы и связанных с ней расстройств | |
| KR20000075697A (ko) | 5-ｈｔ2ａ-길항제로서의 옥사졸리딘 | |
| US4670448A (en) | Triazole amine compounds, their pharmaceutical compositions and method of use | |
| AU622291B2 (en) | (substituted (1,2,3,6-tetrahydropyrid-1-yl)alkyl or thio- alkyl)indoles | |
| KR840001775B1 (ko) | 헤테로 사이클릭 유도체의 제조방법 | |
| NO830643L (no) | Fremgangsmaate for fremstilling av heterocykliske derivater som virker paa histaminreseptorer | |
| US4382929A (en) | Thiophene derivatives and their pharmaceutical compositions and method of use | |
| NL8302450A (nl) | Heterocyclische derivaten; werkwijze voor het bereiden daarvan; farmaceutische preparaten. | |
| BG63206B1 (bg) | Кондензирани тиазолови производни с афинитет към 5-нт рецептори | |
| US4482552A (en) | Triazole compounds and their pharmaceutical use | |
| US4171366A (en) | 1-Naphthothienylalkyl-1H-imidazoles | |
| US4485104A (en) | 1,2,4-Triazole-3-amines and their pharmaceutical use | |
| GB2064515A (en) | Heterocyclic derivatives processes for their production and pharmaceutical compositions containing them | |
| EP0029311B1 (en) | Aminoalkyl benzofuran derivatives, their production and compositions containing them | |
| EP0027744B1 (en) | Thiophene derivatives, processes for the production thereof and pharmaceutical compositions containing them | |
| JP2004502694A (ja) | チエノピロリジノン | |
| US4476126A (en) | 1,2,4 Triazoze amines and their pharmaceutical use | |
| US4777179A (en) | Heterocyclic derivatives, processes for the use thereof and pharmaceutical compositions containing them | |
| CA1069508A (en) | 2-(4-phenyl-4-cyanobuty1)-1,2,3,4-tetrahydro-5(h)-pyrido-(4,3-b)-indoles and processes for their production | |
| NO842577L (no) | Nye 2-substituerte benzofuranderivater. | |
| JPH0219115B2 (sv) |