CA2074180A1 - Thiazole derivatives - Google Patents
Thiazole derivativesInfo
- Publication number
- CA2074180A1 CA2074180A1 CA002074180A CA2074180A CA2074180A1 CA 2074180 A1 CA2074180 A1 CA 2074180A1 CA 002074180 A CA002074180 A CA 002074180A CA 2074180 A CA2074180 A CA 2074180A CA 2074180 A1 CA2074180 A1 CA 2074180A1
- Authority
- CA
- Canada
- Prior art keywords
- ppm
- omega
- substituted
- multiplet
- singlet
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 150000007979 thiazole derivatives Chemical class 0.000 title description 4
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 24
- 150000001875 compounds Chemical class 0.000 claims abstract description 23
- 238000000034 method Methods 0.000 claims abstract description 16
- 238000002360 preparation method Methods 0.000 claims abstract description 14
- 230000008569 process Effects 0.000 claims abstract description 13
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims abstract description 11
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims abstract description 10
- 150000002357 guanidines Chemical class 0.000 claims abstract description 8
- 239000003814 drug Substances 0.000 claims abstract description 6
- 230000007062 hydrolysis Effects 0.000 claims abstract description 6
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 6
- CYEBJEDOHLIWNP-UHFFFAOYSA-N methanethioamide Chemical compound NC=S CYEBJEDOHLIWNP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 206010007559 Cardiac failure congestive Diseases 0.000 claims abstract description 4
- 230000000172 allergic effect Effects 0.000 claims abstract description 4
- 208000010668 atopic eczema Diseases 0.000 claims abstract description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 4
- 238000006698 hydrazinolysis reaction Methods 0.000 claims abstract description 3
- 125000005544 phthalimido group Chemical group 0.000 claims abstract description 3
- 238000006798 ring closing metathesis reaction Methods 0.000 claims abstract description 3
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 26
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- -1 5H-dibenzo-[a,d]-cyclohepten-5-yl group Chemical group 0.000 claims description 14
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 14
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 12
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 11
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 125000000623 heterocyclic group Chemical group 0.000 claims description 8
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 102000003710 Histamine H2 Receptors Human genes 0.000 claims description 6
- 108090000050 Histamine H2 Receptors Proteins 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 125000003277 amino group Chemical group 0.000 claims description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- 238000005893 bromination reaction Methods 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 239000012634 fragment Substances 0.000 claims description 3
- 230000000144 pharmacologic effect Effects 0.000 claims description 3
- 206010019280 Heart failures Diseases 0.000 claims description 2
- 239000005864 Sulphur Substances 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 230000004071 biological effect Effects 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
- 125000005982 diphenylmethyl group Chemical class [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 81
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 59
- 239000000243 solution Substances 0.000 description 59
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 48
- 238000005160 1H NMR spectroscopy Methods 0.000 description 44
- 238000003756 stirring Methods 0.000 description 35
- 238000001816 cooling Methods 0.000 description 31
- 239000011541 reaction mixture Substances 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 26
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 25
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical class NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 22
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 20
- 239000000203 mixture Substances 0.000 description 20
- 229960004132 diethyl ether Drugs 0.000 description 19
- 238000002844 melting Methods 0.000 description 19
- 230000008018 melting Effects 0.000 description 19
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 17
- 238000006243 chemical reaction Methods 0.000 description 17
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- 239000000706 filtrate Substances 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 239000002244 precipitate Substances 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 239000012299 nitrogen atmosphere Substances 0.000 description 12
- 101150056637 Hrh2 gene Proteins 0.000 description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 10
- 229960001340 histamine Drugs 0.000 description 9
- 238000001819 mass spectrum Methods 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 101150041968 CDC13 gene Proteins 0.000 description 8
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 8
- 238000005481 NMR spectroscopy Methods 0.000 description 8
- 230000008570 general process Effects 0.000 description 8
- 229910010272 inorganic material Inorganic materials 0.000 description 8
- 239000011147 inorganic material Substances 0.000 description 8
- 150000003557 thiazoles Chemical class 0.000 description 8
- IFPPZTSKNBSMHN-UHFFFAOYSA-N 2-(3-bromo-4-oxopentyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCC(Br)C(=O)C)C(=O)C2=C1 IFPPZTSKNBSMHN-UHFFFAOYSA-N 0.000 description 7
- 230000000875 corresponding effect Effects 0.000 description 7
- 235000011167 hydrochloric acid Nutrition 0.000 description 7
- 229960000443 hydrochloric acid Drugs 0.000 description 7
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 7
- KISZTEOELCMZPY-UHFFFAOYSA-N 3,3-diphenylpropylamine Chemical compound C=1C=CC=CC=1C(CCN)C1=CC=CC=C1 KISZTEOELCMZPY-UHFFFAOYSA-N 0.000 description 6
- LHVRFUVVRXGZPV-UHFFFAOYSA-N 5-(2-aminoethyl)-4-methyl-2-thiazolamine Chemical compound CC=1N=C(N)SC=1CCN LHVRFUVVRXGZPV-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 102000000543 Histamine Receptors Human genes 0.000 description 6
- 108010002059 Histamine Receptors Proteins 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 235000019439 ethyl acetate Nutrition 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- FWNCNQDIENYPDJ-UHFFFAOYSA-N 2-(4-hydroxybutyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCCCO)C(=O)C2=C1 FWNCNQDIENYPDJ-UHFFFAOYSA-N 0.000 description 5
- DPATUMDQWSJANG-UHFFFAOYSA-N 2-(4-oxopentyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCCC(=O)C)C(=O)C2=C1 DPATUMDQWSJANG-UHFFFAOYSA-N 0.000 description 5
- HVVRQUYSKYIOJV-UHFFFAOYSA-N 2-(5-oxohexyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCCCC(=O)C)C(=O)C2=C1 HVVRQUYSKYIOJV-UHFFFAOYSA-N 0.000 description 5
- CZGOECYPTLSLNI-UHFFFAOYSA-N 6-bromohexan-2-one Chemical compound CC(=O)CCCCBr CZGOECYPTLSLNI-UHFFFAOYSA-N 0.000 description 5
- 239000002178 crystalline material Substances 0.000 description 5
- 229940093499 ethyl acetate Drugs 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- KZZIVOLMJPSDEP-UHFFFAOYSA-N 1-[3-(4-fluorophenyl)-3-pyridin-2-ylpropyl]-2-[3-(1h-imidazol-5-yl)propyl]guanidine Chemical compound C=1N=CNC=1CCCN=C(N)NCCC(C=1N=CC=CC=1)C1=CC=C(F)C=C1 KZZIVOLMJPSDEP-UHFFFAOYSA-N 0.000 description 4
- SUALZDCPKLVMJL-UHFFFAOYSA-N 5-(3-aminopropyl)-1,3-thiazol-2-amine;dihydrochloride Chemical compound Cl.Cl.NCCCC1=CN=C(N)S1 SUALZDCPKLVMJL-UHFFFAOYSA-N 0.000 description 4
- NFHWLPHEKVZKQU-UHFFFAOYSA-N 5-(3-aminopropyl)-4-methyl-1,3-thiazol-2-amine;dihydrochloride Chemical compound Cl.Cl.CC=1N=C(N)SC=1CCCN NFHWLPHEKVZKQU-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 241000700199 Cavia porcellus Species 0.000 description 4
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 4
- SLIKWVTWIGHFJE-UHFFFAOYSA-N diphenoxymethylidenecyanamide Chemical compound C=1C=CC=CC=1OC(=NC#N)OC1=CC=CC=C1 SLIKWVTWIGHFJE-UHFFFAOYSA-N 0.000 description 4
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 4
- 150000002541 isothioureas Chemical class 0.000 description 4
- 230000007935 neutral effect Effects 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- KKKXIWVOUGTUNV-UHFFFAOYSA-N 2-[3-(2-amino-4-methyl-1,3-thiazol-5-yl)propyl]-1-(3,3-diphenylpropyl)guanidine 2,4,6-trinitrophenol Chemical compound C1([N+](=O)[O-])=CC([N+](=O)[O-])=CC([N+](=O)[O-])=C1O.C1([N+](=O)[O-])=CC([N+](=O)[O-])=CC([N+](=O)[O-])=C1O.NC=1SC(=C(N1)C)CCCNC(=N)NCCC(C1=CC=CC=C1)C1=CC=CC=C1 KKKXIWVOUGTUNV-UHFFFAOYSA-N 0.000 description 3
- WNNXALBEELVCMI-UHFFFAOYSA-N 2-bromo-5-(1,3-dioxoisoindol-2-yl)pentanal Chemical compound C1=CC=C2C(=O)N(CCCC(Br)C=O)C(=O)C2=C1 WNNXALBEELVCMI-UHFFFAOYSA-N 0.000 description 3
- BHCHUXXNTHWMGJ-UHFFFAOYSA-N 4-(3-aminopropyl)-1,3-thiazol-2-amine;dihydrochloride Chemical compound Cl.Cl.NCCCC1=CSC(N)=N1 BHCHUXXNTHWMGJ-UHFFFAOYSA-N 0.000 description 3
- WMJZCJDWHBNSLB-UHFFFAOYSA-N 5-(1,3-dioxoisoindol-2-yl)pentanal Chemical compound C1=CC=C2C(=O)N(CCCCC=O)C(=O)C2=C1 WMJZCJDWHBNSLB-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 230000003042 antagnostic effect Effects 0.000 description 3
- JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 3
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 210000005245 right atrium Anatomy 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- DDGHBOLOCQWPKE-UHFFFAOYSA-N 1,3-thiazole;hydrobromide Chemical compound [Br-].C1=CSC=[NH+]1 DDGHBOLOCQWPKE-UHFFFAOYSA-N 0.000 description 2
- GZOILRFVMJAQBC-UHFFFAOYSA-N 2-(3-bromo-4-hydroxybutyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCC(Br)CO)C(=O)C2=C1 GZOILRFVMJAQBC-UHFFFAOYSA-N 0.000 description 2
- PTPZBCHKQSHXQZ-UHFFFAOYSA-N 2-(4-bromo-3-oxobutyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCC(=O)CBr)C(=O)C2=C1 PTPZBCHKQSHXQZ-UHFFFAOYSA-N 0.000 description 2
- PSKJVCNFAMZUFJ-UHFFFAOYSA-N 2-(5-bromo-4-oxopentyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCCC(=O)CBr)C(=O)C2=C1 PSKJVCNFAMZUFJ-UHFFFAOYSA-N 0.000 description 2
- AEQXSCZKSNBLQW-UHFFFAOYSA-N 2-(5-hydroxypentyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCCCCO)C(=O)C2=C1 AEQXSCZKSNBLQW-UHFFFAOYSA-N 0.000 description 2
- VQVGTGLZTBUTQY-UHFFFAOYSA-N 2-[2-(4-methyl-1,3-thiazol-5-yl)ethyl]isoindole-1,3-dione Chemical compound N1=CSC(CCN2C(C3=CC=CC=C3C2=O)=O)=C1C VQVGTGLZTBUTQY-UHFFFAOYSA-N 0.000 description 2
- DNLARIARHLWZRF-UHFFFAOYSA-N 2-[3-(2-amino-4-methyl-1,3-thiazol-5-yl)propyl]-1-(3,3-diphenylpropyl)guanidine Chemical compound N1=C(N)SC(CCCN=C(N)NCCC(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1C DNLARIARHLWZRF-UHFFFAOYSA-N 0.000 description 2
- SLTUYEGLKJHGHO-UHFFFAOYSA-N 2-[3-(2-amino-4-methyl-1,3-thiazol-5-yl)propyl]-1-cyano-3-(3,3-diphenylpropyl)guanidine Chemical compound N1=C(N)SC(CCCN=C(NCCC(C=2C=CC=CC=2)C=2C=CC=CC=2)NC#N)=C1C SLTUYEGLKJHGHO-UHFFFAOYSA-N 0.000 description 2
- BNCFKRVOUNWXAY-UHFFFAOYSA-N 3-(3,4-dichlorophenyl)-3-pyridin-2-ylpropan-1-amine Chemical compound C=1C=CC=NC=1C(CCN)C1=CC=C(Cl)C(Cl)=C1 BNCFKRVOUNWXAY-UHFFFAOYSA-N 0.000 description 2
- LZHGBLUAJMICBZ-UHFFFAOYSA-N 5-(2-aminoethyl)-1,3-thiazol-2-amine Chemical compound NCCC1=CN=C(N)S1 LZHGBLUAJMICBZ-UHFFFAOYSA-N 0.000 description 2
- BKAWJIRCKVUVED-UHFFFAOYSA-N 5-(2-hydroxyethyl)-4-methylthiazole Chemical compound CC=1N=CSC=1CCO BKAWJIRCKVUVED-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 102000004384 Histamine H3 receptors Human genes 0.000 description 2
- 108090000981 Histamine H3 receptors Proteins 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 2
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- TZNOQFCVOYXCAM-UHFFFAOYSA-N [amino(ethylsulfanyl)methylidene]-(3,3-diphenylpropyl)azanium;bromide Chemical compound [Br-].C=1C=CC=CC=1C(CC[NH+]=C(N)SCC)C1=CC=CC=C1 TZNOQFCVOYXCAM-UHFFFAOYSA-N 0.000 description 2
- 229950009330 arpromidine Drugs 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229940005991 chloric acid Drugs 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 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 1
- SWXXKWPYNMZFTE-UHFFFAOYSA-N (c-ethylsulfanylcarbonimidoyl)azanium;bromide Chemical compound Br.CCSC(N)=N SWXXKWPYNMZFTE-UHFFFAOYSA-N 0.000 description 1
- VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical compound BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N 1-butanol Substances CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- ONTXCMXICQNNNO-UHFFFAOYSA-N 2-(3-oxobutyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCC(=O)C)C(=O)C2=C1 ONTXCMXICQNNNO-UHFFFAOYSA-N 0.000 description 1
- TVAQJFUNSFVSGP-UHFFFAOYSA-N 2-(4-methyl-1,3-thiazol-5-yl)ethanamine Chemical compound CC=1N=CSC=1CCN TVAQJFUNSFVSGP-UHFFFAOYSA-N 0.000 description 1
- IPOCGIVMVZXNBQ-UHFFFAOYSA-N 2-[2-(2-amino-1,3-thiazol-4-yl)ethyl]isoindole-1,3-dione;hydrobromide Chemical compound Br.S1C(N)=NC(CCN2C(C3=CC=CC=C3C2=O)=O)=C1 IPOCGIVMVZXNBQ-UHFFFAOYSA-N 0.000 description 1
- LNPILXRCRBMXCD-UHFFFAOYSA-N 2-[2-(2-amino-1,3-thiazol-5-yl)ethyl]isoindole-1,3-dione Chemical compound S1C(N)=NC=C1CCN1C(=O)C2=CC=CC=C2C1=O LNPILXRCRBMXCD-UHFFFAOYSA-N 0.000 description 1
- QAZIDPZKBKDKHT-UHFFFAOYSA-N 2-[3-(2-amino-1,3-thiazol-4-yl)propyl]isoindole-1,3-dione;hydrobromide Chemical compound Br.S1C(N)=NC(CCCN2C(C3=CC=CC=C3C2=O)=O)=C1 QAZIDPZKBKDKHT-UHFFFAOYSA-N 0.000 description 1
- FQEIHIVPLCDSGY-UHFFFAOYSA-N 2-[3-(2-amino-1,3-thiazol-5-yl)propyl]isoindole-1,3-dione;hydrobromide Chemical compound Br.S1C(N)=NC=C1CCCN1C(=O)C2=CC=CC=C2C1=O FQEIHIVPLCDSGY-UHFFFAOYSA-N 0.000 description 1
- YQGBOZHSFVQEPQ-UHFFFAOYSA-N 2-[3-(2-amino-4-methyl-1,3-thiazol-5-yl)propyl]isoindole-1,3-dione;hydrobromide Chemical compound Br.N1=C(N)SC(CCCN2C(C3=CC=CC=C3C2=O)=O)=C1C YQGBOZHSFVQEPQ-UHFFFAOYSA-N 0.000 description 1
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
- XMNSDCYVLIMUOT-UHFFFAOYSA-N 2-bromo-4-(1,3-dioxoisoindol-2-yl)butanal Chemical compound C1=CC=C2C(=O)N(CCC(Br)C=O)C(=O)C2=C1 XMNSDCYVLIMUOT-UHFFFAOYSA-N 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- GQAFTAYUUOBTRK-UHFFFAOYSA-N 3,5,5-trimethyl-4H-pyrazole-1-carbothioamide Chemical compound CC1=NN(C(N)=S)C(C)(C)C1 GQAFTAYUUOBTRK-UHFFFAOYSA-N 0.000 description 1
- CSJHCQDRYAUEQH-UHFFFAOYSA-N 3-(4-methyl-1,3-thiazol-2-yl)propan-1-amine;dihydrochloride Chemical compound Cl.Cl.CC1=CSC(CCCN)=N1 CSJHCQDRYAUEQH-UHFFFAOYSA-N 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- KDHWOCLBMVSZPG-UHFFFAOYSA-N 3-imidazol-1-ylpropan-1-amine Chemical compound NCCCN1C=CN=C1 KDHWOCLBMVSZPG-UHFFFAOYSA-N 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- WMXADABRNBNSJC-UHFFFAOYSA-N 4-(1,3-dioxoisoindol-2-yl)butanal Chemical compound C1=CC=C2C(=O)N(CCCC=O)C(=O)C2=C1 WMXADABRNBNSJC-UHFFFAOYSA-N 0.000 description 1
- IOXZFXWMILDPTH-UHFFFAOYSA-N 4-(3-aminopropyl)-1,3-thiazol-2-amine Chemical compound NCCCC1=CSC(N)=N1 IOXZFXWMILDPTH-UHFFFAOYSA-N 0.000 description 1
- BLFRQYKZFKYQLO-UHFFFAOYSA-N 4-aminobutan-1-ol Chemical compound NCCCCO BLFRQYKZFKYQLO-UHFFFAOYSA-N 0.000 description 1
- HXHGULXINZUGJX-UHFFFAOYSA-N 4-chlorobutanol Chemical compound OCCCCCl HXHGULXINZUGJX-UHFFFAOYSA-N 0.000 description 1
- QMHIMXFNBOYPND-UHFFFAOYSA-N 4-methylthiazole Chemical compound CC1=CSC=N1 QMHIMXFNBOYPND-UHFFFAOYSA-N 0.000 description 1
- AGNFWIZBEATIAK-UHFFFAOYSA-N 4-phenylbutylamine Chemical compound NCCCCC1=CC=CC=C1 AGNFWIZBEATIAK-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical compound [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
- NQUYKSNCKIXTQF-UHFFFAOYSA-N 5-(2-aminoethyl)-4-methyl-1,3-thiazol-2-amine;dihydrochloride Chemical compound Cl.Cl.CC=1N=C(N)SC=1CCN NQUYKSNCKIXTQF-UHFFFAOYSA-N 0.000 description 1
- BHBQCSAJEKMSPN-UHFFFAOYSA-N 5-(2-bromoethyl)-4-methyl-1,3-thiazole;hydrobromide Chemical compound Br.CC=1N=CSC=1CCBr BHBQCSAJEKMSPN-UHFFFAOYSA-N 0.000 description 1
- RIOVLKQWIKRBIB-UHFFFAOYSA-N 5-(3-aminopropyl)-4-methyl-1,3-thiazol-2-amine Chemical compound CC=1N=C(N)SC=1CCCN RIOVLKQWIKRBIB-UHFFFAOYSA-N 0.000 description 1
- LQGKDMHENBFVRC-UHFFFAOYSA-N 5-aminopentan-1-ol Chemical compound NCCCCCO LQGKDMHENBFVRC-UHFFFAOYSA-N 0.000 description 1
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 241000208199 Buxus sempervirens Species 0.000 description 1
- NEDHHMJNFMKLBT-UHFFFAOYSA-N C1([N+](=O)[O-])=CC([N+](=O)[O-])=CC([N+](=O)[O-])=C1O.C1([N+](=O)[O-])=CC([N+](=O)[O-])=CC([N+](=O)[O-])=C1O.NC=1SC(=C(N1)C)CCCNC(=N)NCCCC1=CC=CC=C1 Chemical compound C1([N+](=O)[O-])=CC([N+](=O)[O-])=CC([N+](=O)[O-])=C1O.C1([N+](=O)[O-])=CC([N+](=O)[O-])=CC([N+](=O)[O-])=C1O.NC=1SC(=C(N1)C)CCCNC(=N)NCCCC1=CC=CC=C1 NEDHHMJNFMKLBT-UHFFFAOYSA-N 0.000 description 1
- SMIKUIMODNMCCG-UHFFFAOYSA-N C1([N+](=O)[O-])=CC([N+](=O)[O-])=CC([N+](=O)[O-])=C1O.C1([N+](=O)[O-])=CC([N+](=O)[O-])=CC([N+](=O)[O-])=C1O.NC=1SC=C(N1)CCCNC(=N)NCCC(C1=CC=CC=C1)C1=CC=CC=C1 Chemical compound C1([N+](=O)[O-])=CC([N+](=O)[O-])=CC([N+](=O)[O-])=C1O.C1([N+](=O)[O-])=CC([N+](=O)[O-])=CC([N+](=O)[O-])=C1O.NC=1SC=C(N1)CCCNC(=N)NCCC(C1=CC=CC=C1)C1=CC=CC=C1 SMIKUIMODNMCCG-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 102100021757 E3 ubiquitin-protein ligase RNF135 Human genes 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- 102000003834 Histamine H1 Receptors Human genes 0.000 description 1
- 108090000110 Histamine H1 Receptors Proteins 0.000 description 1
- 101001106984 Homo sapiens E3 ubiquitin-protein ligase RNF135 Proteins 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- 241000529738 Picris Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000004103 aminoalkyl group Chemical group 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- CPEKAXYCDKETEN-UHFFFAOYSA-N benzoyl isothiocyanate Chemical compound S=C=NC(=O)C1=CC=CC=C1 CPEKAXYCDKETEN-UHFFFAOYSA-N 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 1
- 230000002213 calciumantagonistic effect Effects 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229960004424 carbon dioxide Drugs 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- XTEGARKTQYYJKE-UHFFFAOYSA-N chloric acid Chemical compound OCl(=O)=O XTEGARKTQYYJKE-UHFFFAOYSA-N 0.000 description 1
- 230000002057 chronotropic effect Effects 0.000 description 1
- AQIXAKUUQRKLND-UHFFFAOYSA-N cimetidine Chemical compound N#C/N=C(/NC)NCCSCC=1N=CNC=1C AQIXAKUUQRKLND-UHFFFAOYSA-N 0.000 description 1
- 229960001380 cimetidine Drugs 0.000 description 1
- 239000003245 coal Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 229940000425 combination drug Drugs 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 235000019628 coolness Nutrition 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229910000071 diazene Inorganic materials 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- OLHQOJYVQUNWPL-UHFFFAOYSA-N dimaprit Chemical class CN(C)CCCSC(N)=N OLHQOJYVQUNWPL-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
- LUOYACCQSOFAAA-UHFFFAOYSA-N ethyl 6-methyl-3,6-dihydro-2h-pyran-5-carboxylate Chemical compound CCOC(=O)C1=CCCOC1C LUOYACCQSOFAAA-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 229940083094 guanine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
- 210000002837 heart atrium Anatomy 0.000 description 1
- 239000003386 histamine H2 receptor agonist Substances 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- MURRAGMMNAYLNA-UHFFFAOYSA-N impromidine Chemical compound N1C=NC(CSCCNC(N)=NCCCC=2NC=NC=2)=C1C MURRAGMMNAYLNA-UHFFFAOYSA-N 0.000 description 1
- 229950005073 impromidine Drugs 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000000297 inotrophic effect Effects 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- VKFHVRIEURVUHM-UHFFFAOYSA-N n-(diphenoxymethylidene)benzamide Chemical compound C=1C=CC=CC=1C(=O)N=C(OC=1C=CC=CC=1)OC1=CC=CC=C1 VKFHVRIEURVUHM-UHFFFAOYSA-N 0.000 description 1
- 150000002829 nitrogen Chemical group 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen(.) Chemical compound [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/40—Unsubstituted amino or imino radicals
-
- 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
- C07D417/06—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 carbon chain containing only aliphatic carbon atoms
-
- 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NL9000132 | 1990-01-19 | ||
| NL9000132A NL9000132A (nl) | 1990-01-19 | 1990-01-19 | Nieuwe thiazoolderivaten. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2074180A1 true CA2074180A1 (en) | 1991-07-20 |
Family
ID=19856444
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002074180A Abandoned CA2074180A1 (en) | 1990-01-19 | 1991-01-18 | Thiazole derivatives |
| CA002074175A Abandoned CA2074175A1 (en) | 1990-01-19 | 1991-01-18 | Thiazole derivatives |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002074175A Abandoned CA2074175A1 (en) | 1990-01-19 | 1991-01-18 | Thiazole derivatives |
Country Status (9)
| Country | Link |
|---|---|
| EP (2) | EP0511270A1 (nl) |
| JP (2) | JPH05503096A (nl) |
| AU (2) | AU7064491A (nl) |
| CA (2) | CA2074180A1 (nl) |
| IE (2) | IE910172A1 (nl) |
| IL (2) | IL96998A0 (nl) |
| NL (1) | NL9000132A (nl) |
| WO (2) | WO1991010657A1 (nl) |
| ZA (2) | ZA91418B (nl) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BRPI0507485A (pt) * | 2004-02-05 | 2007-07-10 | Probiodrug Ag | inibidores novos de glutaminil ciclase |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2636037A (en) * | 1947-10-10 | 1953-04-21 | Sharp & Dohme Inc | 2-amino-4-piperidinoethyl-thiazole |
| FR2073427A1 (en) * | 1969-11-28 | 1971-10-01 | Sogeras | 4-methyl-5-ethyl-n-heterocyclic thiazoles - with antianoxic activity |
| FR2361111A1 (fr) * | 1976-08-11 | 1978-03-10 | Roussel Uclaf | Nouveaux derives de 5-thiazole alkylamine, un procede pour leur preparation et leur application comme medicaments |
| US4166860A (en) * | 1977-10-11 | 1979-09-04 | William H. Rorer, Inc. | Imidazole amidinoureas for stimulating H2 -receptors |
| US4474794A (en) * | 1982-03-19 | 1984-10-02 | Eli Lilly And Company | N-Thiazolylmethylthioalkyl-N1 -alkenyl (or alkynyl)guanidines and related compounds |
| NL8601585A (nl) * | 1986-06-19 | 1988-01-18 | Vereniging Voor Christelijk Wetenschappelijk Onderwijs | N-(2-gesubstitueerde alkyl)-n-imidazol-4-yl alkyl guanidine. |
| NL8800998A (nl) * | 1988-04-18 | 1989-11-16 | Cedona Pharm Bv | Werkwijze voor het bereiden van een al of niet gesubstitueerd 4(5)-(omega-aminoalkyl) imidazool. |
-
1990
- 1990-01-19 NL NL9000132A patent/NL9000132A/nl not_active Application Discontinuation
-
1991
- 1991-01-18 AU AU70644/91A patent/AU7064491A/en not_active Abandoned
- 1991-01-18 CA CA002074180A patent/CA2074180A1/en not_active Abandoned
- 1991-01-18 CA CA002074175A patent/CA2074175A1/en not_active Abandoned
- 1991-01-18 JP JP3502574A patent/JPH05503096A/ja active Pending
- 1991-01-18 EP EP91902804A patent/EP0511270A1/en not_active Withdrawn
- 1991-01-18 IE IE017291A patent/IE910172A1/en unknown
- 1991-01-18 WO PCT/NL1991/000008 patent/WO1991010657A1/en not_active Application Discontinuation
- 1991-01-18 WO PCT/NL1991/000007 patent/WO1991010656A1/en not_active Application Discontinuation
- 1991-01-18 IE IE017191A patent/IE910171A1/en unknown
- 1991-01-18 AU AU70581/91A patent/AU7058191A/en not_active Abandoned
- 1991-01-18 JP JP3502573A patent/JPH05503694A/ja active Pending
- 1991-01-18 EP EP91902805A patent/EP0511271A1/en not_active Withdrawn
- 1991-01-21 ZA ZA91418A patent/ZA91418B/xx unknown
- 1991-01-21 ZA ZA91419A patent/ZA91419B/xx unknown
- 1991-01-22 IL IL96998A patent/IL96998A0/xx unknown
- 1991-01-22 IL IL96997A patent/IL96997A0/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IL96998A0 (en) | 1992-03-29 |
| JPH05503694A (ja) | 1993-06-17 |
| JPH05503096A (ja) | 1993-05-27 |
| ZA91419B (en) | 1991-10-30 |
| CA2074175A1 (en) | 1991-07-20 |
| EP0511270A1 (en) | 1992-11-04 |
| IE910172A1 (en) | 1991-07-31 |
| AU7064491A (en) | 1991-08-05 |
| ZA91418B (en) | 1991-10-30 |
| EP0511271A1 (en) | 1992-11-04 |
| NL9000132A (nl) | 1991-08-16 |
| WO1991010656A1 (en) | 1991-07-25 |
| IE910171A1 (en) | 1991-07-31 |
| IL96997A0 (en) | 1992-03-29 |
| AU7058191A (en) | 1991-08-05 |
| WO1991010657A1 (en) | 1991-07-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| FI76795C (fi) | Foerfarande foer framstaellning av nya, terapeutiskt anvaendbara 3,4-disubstituerade 1,2,5-tiadiazol-1-oxider och -1,1-dioxider samt nya mellanprodukter. | |
| US4560690A (en) | 2-(N-substituted guanidino)-4-hetero-arylthiazole antiulcer agents | |
| NO329617B1 (no) | Tiazolderivater med CB1-antagonistisk, agonistisk eller partiell agonistisk aktivitet | |
| NO170883B (no) | Fremgangsmaate for fremstilling av 2-amino-5-hydroksy-4-metylpyrimidin-derivater | |
| CA2306811A1 (en) | Piperazine compounds and medicinal use thereof | |
| NO158419B (no) | Analogifremgangsmaate til fremstilling av terapeutisk aktive 1,2-diaminocyklobuten-3,4-dioner. | |
| CA2185082A1 (en) | Azole derivatives, their use, production and usage | |
| KR20020003559A (ko) | Ｌｆａ-1의 ｉｃａｍ에 대한 결합 저해제 및 그 용도 | |
| US6586456B1 (en) | Aminothiazole derivatives and their use as CRF receptor ligands | |
| CA1310966C (en) | Substituted 1-(h-imidazol-4-yl)alkyl-benzamides | |
| NO151322B (no) | Analogifremgangsmaate for fremstilling av terapeutisk aktive 2(5-metyl-4-imidazolyl-metyltio)etylamino-(no2-heterocyklisk gruppe) forbindelser | |
| HU182461B (en) | Process for producing new h-2 down-receptore antagonistic thiazole derivatives | |
| NO885117L (no) | Substituerte hydroksylaminer. | |
| EP0234011A1 (en) | 4-(1,2,5,6-tetrahydro-1-alkyl-3-pyridinyl)-2-thiazolamines and 4-(hexahydro-1-alkyl-3-pyridinyl)-2-thiazolamines | |
| US4935424A (en) | 4 or 5-(substituted piperazinylalkyl)-2-aminothiazoles as antipsychotic agents | |
| CA2074180A1 (en) | Thiazole derivatives | |
| US4692531A (en) | Substituted 3,4-diamino-1,2,5-thiadiazoles having histamine H2 -receptor antagonist activity | |
| DD295373A5 (de) | Verfahren zur herstellung von alpha-cyan-beta-oxopropionamiden | |
| Suzuki et al. | Syntheses of 2-Aryl-4-(3-thienyl) imidazole Derivatives with Antiinflammatory Preperties | |
| CS197238B2 (en) | Method of producing novel acylated derivatives of 2-amino thiazole | |
| SU535906A3 (ru) | Способ получени производных 2-аминотиазола | |
| JPH0578339A (ja) | 中間体化合物 | |
| NO122530B (nl) | ||
| NO148556B (no) | Analogifremgangsmaate for fremstilling av farmakologisk aktive triazinoner. | |
| KR870000924B1 (ko) | 2-(n-치환된 구아니디노)-4-헤테로아릴티아졸의 제조방법 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |