JP4533383B2 - カプサイシン誘導体並びにその製造及び使用 - Google Patents
カプサイシン誘導体並びにその製造及び使用 Download PDFInfo
- Publication number
- JP4533383B2 JP4533383B2 JP2006526038A JP2006526038A JP4533383B2 JP 4533383 B2 JP4533383 B2 JP 4533383B2 JP 2006526038 A JP2006526038 A JP 2006526038A JP 2006526038 A JP2006526038 A JP 2006526038A JP 4533383 B2 JP4533383 B2 JP 4533383B2
- Authority
- JP
- Japan
- Prior art keywords
- capsaicin
- formula
- represented
- paint
- carboxylic acid
- 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.)
- Active
Links
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical class COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 title claims abstract description 78
- 238000004519 manufacturing process Methods 0.000 title abstract description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 25
- -1 capsaicin derivates Chemical class 0.000 claims abstract description 16
- 238000000034 method Methods 0.000 claims abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims description 15
- WRPWWVNUCXQDQV-UHFFFAOYSA-N vanillylamine Chemical compound COC1=CC(CN)=CC=C1O WRPWWVNUCXQDQV-UHFFFAOYSA-N 0.000 claims description 11
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 229940053939 vanillylamine Drugs 0.000 claims description 8
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 6
- 125000006239 protecting group Chemical group 0.000 claims description 2
- 150000001735 carboxylic acids Chemical class 0.000 claims 2
- SXXLKZCNJHJYFL-UHFFFAOYSA-N 4,5,6,7-tetrahydro-[1,2]oxazolo[4,5-c]pyridin-5-ium-3-olate Chemical compound C1CNCC2=C1ONC2=O SXXLKZCNJHJYFL-UHFFFAOYSA-N 0.000 claims 1
- SWYCSFHXRGKNBP-UHFFFAOYSA-N 5-iodopentan-1-ol Chemical compound OCCCCCI SWYCSFHXRGKNBP-UHFFFAOYSA-N 0.000 claims 1
- 101000799461 Homo sapiens Thrombopoietin Proteins 0.000 claims 1
- 102100034195 Thrombopoietin Human genes 0.000 claims 1
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 claims 1
- 230000001590 oxidative effect Effects 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- UORVCLMRJXCDCP-UHFFFAOYSA-N propynoic acid Chemical compound OC(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-N 0.000 claims 1
- 239000003973 paint Substances 0.000 abstract description 44
- 235000017663 capsaicin Nutrition 0.000 abstract description 37
- 229960002504 capsaicin Drugs 0.000 abstract description 37
- 239000005871 repellent Substances 0.000 abstract description 23
- 238000000576 coating method Methods 0.000 abstract description 9
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 238000009434 installation Methods 0.000 abstract 1
- 230000002940 repellent Effects 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
- 230000000813 microbial effect Effects 0.000 description 15
- 239000000047 product Substances 0.000 description 14
- PIILXFBHQILWPS-UHFFFAOYSA-N tributyltin Chemical compound CCCC[Sn](CCCC)CCCC PIILXFBHQILWPS-UHFFFAOYSA-N 0.000 description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 239000000126 substance Substances 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 239000000203 mixture Substances 0.000 description 11
- 239000002994 raw material Substances 0.000 description 11
- 238000004809 thin layer chromatography Methods 0.000 description 10
- OXPQXCWBBDMQRS-UHFFFAOYSA-N 7-phenylhept-6-ynoic acid Chemical compound OC(=O)CCCCC#CC1=CC=CC=C1 OXPQXCWBBDMQRS-UHFFFAOYSA-N 0.000 description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 9
- 230000003373 anti-fouling effect Effects 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- 241000238586 Cirripedia Species 0.000 description 7
- 241000237536 Mytilus edulis Species 0.000 description 7
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- 125000003118 aryl group Chemical group 0.000 description 7
- 239000000284 extract Substances 0.000 description 7
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 6
- DCBJCKDOZLTTDW-UHFFFAOYSA-N 5-chloropentan-1-ol Chemical compound OCCCCCCl DCBJCKDOZLTTDW-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 125000003342 alkenyl group Chemical group 0.000 description 6
- 125000003545 alkoxy group Chemical group 0.000 description 6
- 125000004414 alkyl thio group Chemical group 0.000 description 6
- 125000000304 alkynyl group Chemical group 0.000 description 6
- 125000003435 aroyl group Chemical group 0.000 description 6
- 125000005110 aryl thio group Chemical group 0.000 description 6
- 125000004104 aryloxy group Chemical group 0.000 description 6
- 125000001589 carboacyl group Chemical group 0.000 description 6
- 125000004093 cyano group Chemical group *C#N 0.000 description 6
- 125000000392 cycloalkenyl group Chemical group 0.000 description 6
- 125000000753 cycloalkyl group Chemical group 0.000 description 6
- 125000001475 halogen functional group Chemical group 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 6
- 125000004043 oxo group Chemical group O=* 0.000 description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 6
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 6
- WLHOOFDTKPBKIY-UHFFFAOYSA-N 2-(5-chloropentoxy)oxane Chemical compound ClCCCCCOC1CCCCO1 WLHOOFDTKPBKIY-UHFFFAOYSA-N 0.000 description 5
- SBZBBXGHTUXYOO-UHFFFAOYSA-N 2-(7-phenylhept-6-ynoxy)oxane Chemical compound C=1C=CC=CC=1C#CCCCCCOC1CCCCO1 SBZBBXGHTUXYOO-UHFFFAOYSA-N 0.000 description 5
- 230000004071 biological effect Effects 0.000 description 5
- 239000011248 coating agent Substances 0.000 description 5
- ZDXUSVVNVXTSHB-UHFFFAOYSA-N 2-(5-iodopentoxy)oxane Chemical compound ICCCCCOC1CCCCO1 ZDXUSVVNVXTSHB-UHFFFAOYSA-N 0.000 description 4
- 241001629057 Amphibalanus improvisus Species 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 235000020638 mussel Nutrition 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 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 3
- 235000002566 Capsicum Nutrition 0.000 description 3
- 240000004160 Capsicum annuum Species 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000000556 factor analysis Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 239000008601 oleoresin Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 239000013535 sea water Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 238000004381 surface treatment Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 3
- 0 *C#CCCCCC(N)=O Chemical compound *C#CCCCCC(N)=O 0.000 description 2
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 2
- TZZAKSLHHIJRLL-UHFFFAOYSA-N 4-hydroxy-3-methoxybenzamide Chemical class COC1=CC(C(N)=O)=CC=C1O TZZAKSLHHIJRLL-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 235000008534 Capsicum annuum var annuum Nutrition 0.000 description 2
- 235000002283 Capsicum annuum var aviculare Nutrition 0.000 description 2
- 235000013303 Capsicum annuum var. frutescens Nutrition 0.000 description 2
- 235000002284 Capsicum baccatum var baccatum Nutrition 0.000 description 2
- 235000002568 Capsicum frutescens Nutrition 0.000 description 2
- 241000195493 Cryptophyta Species 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 239000006002 Pepper Substances 0.000 description 2
- 241000722363 Piper Species 0.000 description 2
- 235000016761 Piper aduncum Nutrition 0.000 description 2
- 235000017804 Piper guineense Nutrition 0.000 description 2
- 235000008184 Piper nigrum Nutrition 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 150000001345 alkine derivatives Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000000845 anti-microbial effect Effects 0.000 description 2
- 239000004599 antimicrobial Substances 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 2
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 239000000446 fuel Substances 0.000 description 2
- AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 2
- GNSLYOGEBCFYDE-UHFFFAOYSA-N lithium;ethynylbenzene Chemical compound [Li+].[C-]#CC1=CC=CC=C1 GNSLYOGEBCFYDE-UHFFFAOYSA-N 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 235000012141 vanillin Nutrition 0.000 description 2
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 2
- 239000002023 wood Substances 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- KZMAWJRXKGLWGS-UHFFFAOYSA-N 2-chloro-n-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]-n-(3-methoxypropyl)acetamide Chemical compound S1C(N(C(=O)CCl)CCCOC)=NC(C=2C=CC(OC)=CC=2)=C1 KZMAWJRXKGLWGS-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical group [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 1
- 240000008574 Capsicum frutescens Species 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
- 238000005967 Finkelstein reaction Methods 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 241000237858 Gastropoda Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
- 229920005372 Plexiglas® Polymers 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 241000722921 Tulipa gesneriana Species 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000009360 aquaculture Methods 0.000 description 1
- 244000144974 aquaculture Species 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 239000003139 biocide Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000001390 capsicum minimum Substances 0.000 description 1
- VZDYWEUILIUIDF-UHFFFAOYSA-J cerium(4+);disulfate Chemical compound [Ce+4].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O VZDYWEUILIUIDF-UHFFFAOYSA-J 0.000 description 1
- 229910000355 cerium(IV) sulfate Inorganic materials 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
- 229960005091 chloramphenicol Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 239000003269 fluorescent indicator Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 239000002581 neurotoxin Substances 0.000 description 1
- 231100000618 neurotoxin Toxicity 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- WUAWDNVSABPBSI-UHFFFAOYSA-N sodium;ethynylbenzene Chemical compound [Na+].[C-]#CC1=CC=CC=C1 WUAWDNVSABPBSI-UHFFFAOYSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
- C09D5/00—Coating compositions, e.g. paints, varnishes or lacquers, characterised by their physical nature or the effects produced; Filling pastes
- C09D5/16—Antifouling paints; Underwater paints
- C09D5/1606—Antifouling paints; Underwater paints characterised by the anti-fouling agent
- C09D5/1612—Non-macromolecular compounds
- C09D5/1625—Non-macromolecular compounds organic
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/18—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group —CO—N<, e.g. carboxylic acid amides or imides; Thio analogues thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/16—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
- C07C233/17—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/22—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
- C09D5/00—Coating compositions, e.g. paints, varnishes or lacquers, characterised by their physical nature or the effects produced; Filling pastes
- C09D5/14—Paints containing biocides, e.g. fungicides, insecticides or pesticides
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09D—COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR
- C09D5/00—Coating compositions, e.g. paints, varnishes or lacquers, characterised by their physical nature or the effects produced; Filling pastes
- C09D5/16—Antifouling paints; Underwater paints
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Plant Pathology (AREA)
- Materials Engineering (AREA)
- Agronomy & Crop Science (AREA)
- Pest Control & Pesticides (AREA)
- Health & Medical Sciences (AREA)
- Dentistry (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Paints Or Removers (AREA)
Description
Dray,N.S.,Biochemical Pharmacology,44,(1992),611
カプサイシンの生物学的活性を明らかにするために、次に記載するように生物学的実験を実施した。この実験により、カプサイシンが前述の生物学的活性と本発明の効果とを有することが示される。他の船底物質又は塗料において、カプサイシン及び/又は他の式(1)で表される化合物は、本実験での使用濃度において他の活性も達成した。
殺生物剤を含まないと表示されている船底塗料商品にカプサイシンを配合する。この塗料の商標は「Fabio EcoTM」であり、International Paint、Akzo−Nobelの製品である。塗料1kg当たりのカプサイシン濃度を、0g、1g及び5gの3濃度とした。まずカプサイシンをシンナー(International No.3)(10mL)に溶解し、次に塗料に混合した。Fabio Ecoとシンナー(10mL)のみの混合物を対照として用いた。塗料混合物は塗布前に一時間静置した。この塗料を複数のプレキシガラスパネル(11×11×0.2cm)に塗布した。
計15枚のパネルに塗布した。
パネル(5枚)は対照塗料(0g/kg カプサイシン)
パネル(5枚)は塗料(1g/kg カプサイシン)
パネル(5枚)は塗料(5g/kg カプサイシン)
パネルを次のように分析した。パネルは写真撮影した。
フジツボ(Balanus improvisus)による被覆率を評価した。ムラサキイガイ(Mytilus edulis)による被覆率を評価した。パネル上の全生育物を掻き落とし、湿重量を測定した。
実験結果を図1〜6に示す。これらから、塗料1kg当り5gのカプサイシン濃度で処理すると、対照処理に比べ有意に生育を低減させることがわかった。
新規化合物の合成について以下詳細に説明する。本明細書末尾の文献リストに掲げた文献の一部を参照する。カプサイシン及び他のカプサイシノイドの合成法が数種知られている5-9。本発明においてはカプサイシンの海洋微生物に対する生物学的活性が特に注目されている。より強力なカプサイシノイドを製造するためにカプサイシン誘導体の合成方法を開発した。この合成方法においては、炭素−炭素二重結合を炭素−炭素三重結合に置き換えた。合成方法全体をスキーム1に示す。
カプサイシンアルキン類似体の合成方法はアルキン原料8(R=アリール、アルキル等)に対して一般的である。R基を変更することにより、種々のカプサイシンアルキン類似体を合成することができ、それによって生物学的活性を評価することができる。第一の標的分子1(R=Ph)は、アルキンフェニルアセチレン(8:R=Ph)、4−ヒドロキシ−3−メトキシベンズアルデヒド(バニリン)(4)及び5−クロロ−1−ペンタノール(11)を原料として生産する。4−アミノメチル−2−メトキシフェノール(バニリルアミン)(2)は、文献記載のようにバニリン(4)から合成した6。5−クロロ−l−ペンタノール(11)は、標準的条件下でまずTHPエーテルとして保護した10、11。対応するTHPエーテル(10)が収率95%で生成した。THF中でリチウムフェニルアセチリドを用いた置換反応(SN2)を試みたが、所望の生成物(7)は得られなかった。これは、リチウムフェニルアセチリドが塩基として反応し、HClの10からの脱離(E2)が観察され、これにより対応するアルケンが唯一の生成物として得られたことによる。ナトリウムフェニルアセチリドにおいても同じ結果となった。この問題は、フィンケルシュタイン反応により10を対応するヨウ素体9に転化することにより解決された11-13。このようにして置換反応がうまく進行して、アルキン7が収率85%で生成した。7におけるTHP保護を酸触媒存在下で除去すると10、アルコール6がほぼ定量的収率(97%)で得られた。ブラウンのクロム酸酸化の改変法14によりカルボン酸5を90%の収率で得た。5は更にチオニルクロライドと反応し、対応する酸クロライド3を収率85%で生成した。この酸クロライド(3)とバニリルアミン(2)とのカップリング反応により、目的分子である7−フェニルヘプタ−6−イン−酸−4−ヒドロキシ−3−メトキシベンジルアミド(1)を収率86%で得た。この化合物は本発明者の知る限りこれまでに合成されたことはない。本発明者らは、化合物1の慣用名としてフェニルカプサイシンを提案する。
全般
NMRスペクトル(300MHz 1H−NMRスペクトル及び75MHz 13C−NMRスペクトル)はバリアン300MHzスペクトロメーターを用いて得た。トリメチルシラン(TMS)を内部標準として用いた。1H−NMRスペクトルの化学シフトはTMSに対する相対値(ppm)である。13C−NMRスペクトルは重クロロホルム(δ76.9ppm)に対する相対値(ppm)である。薄層クロマトグラフィーはフルカ社のシリカゲルプレート(蛍光指示薬を有するシリカゲル/DCアルフォリンシリカゲル、商品番号60778)上で行った。スポットはUV光(λ=254nm)、MOP試薬(モリブダトリン酸(14g)/エタノール(125mL))又はCER−MOP試薬(モリブダトリン酸(5g)、硫酸セリウム(IV)(2g)及び98%H2SO4(16mL)/水(180mL))で検出し、熱風銃でシリカゲルプレートを加熱して展開した。薬品類は、フルカ、シグマ・アルドリッチ、アクロス、メルク及びランカスター社の商品を用いた。必要に応じて標準的な乾燥方法を採用した。無水テトラヒドロフランは、アルゴン雰囲気下でナトリウム−ベンゾフェノン−ケチルを用いて得た。
5−クロロ−1−ペンタノール(12.26g、0.1mol)を無水ジクロロメタン(400mL)に溶解した。3,4−ジヒドロ−2H−ピラン(12.62g、0.15mol)及びピリジントルエン−4−スルホネート(1.26g、5mmol)を反応液に添加し、窒素雰囲気下室温で一晩磁気的手段で攪拌した。炭酸水素ナトリウム飽和溶液(150mL)を添加し、分相した。水相をジクロロメタンで抽出(4×25mL)した。ジクロロメタン相を合一し、水で洗浄(2×20mL)した後、MgSO4で乾燥させた。ジクロロメタンをロータリーエバポレータで留去し、19.6gの淡黄色の油状物を得た(収率95%)。NMRから、純物質であることが確認された。
2−(5−クロロペンチルオキシ)テトラヒドロ−2H−ピラン(10)(20.67g、0.1mol)の無水アセトン(50mL)溶液を、磁気的手段で攪拌されたヨウ化ナトリウム(16.49g、0.11mol)の無水アセトン(150mL)溶液に滴下した。反応液を窒素雰囲気下で一晩還流した。冷却後析出した塩化ナトリウムを濾去し、アセトンをロータリーエバポレータで留去した。残渣は少量の塩化ナトリウムを含んでいたが、これを無水ペンタン(200mL)に溶解した。塩化ナトリウムを濾去し、ペンタンをロータリーエバポレータで留去し、26.2gの黄褐色の油状物を得た(収率88%)。NMRから、純物質であることが確認された。
BuLi(33.3mL、50mmol、1.5M)を、磁気的手段で攪拌されたフェニルアセチレン(5.11g、50mmol)の無水テトラヒドロフラン(200mL)溶液に窒素雰囲気下0℃で滴下した。BuLi全量を添加した後、反応液を0℃で30分攪拌した。2−(5−ヨードペンチルオキシ)テトラヒドロ−2H−ピラン(9)(14.91g、50mmol)の無水テトラヒドロフラン(100mL)溶液を0℃で滴下した。添加終了後反応液を室温に戻し、一晩還流した。反応を薄層クロマトグラフィー(TLC)でモニターした。原料の全量が転化された後、水(300mL)を添加し、水相を石油エーテル(沸点40〜60℃)(6×50mL)で抽出した。有機相を合一し、水で洗浄(4×25mL)した後、MgSO4で乾燥させた。石油エーテルをロータリーエバポレータで留去し、11.6gの生成物を得た(収率85%)。NMRから、純物質であることが確認されたので、更なる精製は必要なかった。
磁気的手段で攪拌された2−(7−フェニルヘプタ−6−イニルオキシ)テトラヒドロ−2H−ピラン(7)(13.62g、50mmol)の無水メタノール(300mL)溶液にピリジントルエン−4−スルホネート(0.75g、3mmol)を添加した。反応液を55℃で攪拌し、TLCでモニターした。原料の全量が転化した後、メタノールをロータリーエバポレータで留去し、水(200mL)を得られた残渣の加えた。水相を石油エーテル(沸点40〜60℃)/Et2O 1:1(5×50mL)で抽出した。有機相を合一し、水で洗浄(2×20mL)した後、MgS04で乾燥させた。ロータリーエバポレータで留去し、9.1gの黄色の粘稠油状物を得た(収率97%)。TLC及びNMRから、純物質であることが確認された。
7−フェニルヘプタ−6−イン−1−オール(6)(7.53g、40mmol)のアセトン(400mL)溶液を磁気的手段で攪拌し、該溶液にブラウンのクロム酸試薬(133mL、88mmol、0.66M)を0℃で徐々に滴下した。クロム酸の添加後、反応液を0℃で一時間攪拌し、原料全てが転化されたことがTLCで確認されるまで室温で攪拌した。水(300mL)を添加し、水相を石油エーテル(沸点40〜60℃)/Et2O 1:1(6×50mL)で抽出した。有機相を合一し、水で洗浄(2×25mL)した後、MgSO4で乾燥させた。ロータリーエバポレータで留去し、7.3gの淡黄色の粘稠油状物を得た(収率90%)。この油状物を放置すると結晶化した。TLC及びNMRから、純物質であることが確認された。
7−フェニルヘプタ−6−イン酸(5)(4.05g、20mmol)とチオニルクロライド(7.14g、60mmol)との混合物を磁気的手段で攪拌し、2時間還流した(100℃)。過剰のチオニルクロライドをロータリーエバポレータで除去し、3.7gの褐色油状物を得た(収率85%)。TLC及びNMRから、純物質であることが確認された。
文献記載に従って、100mmolスケールでバニリルアミンを合成した6。
バニリルアミン(2)(3.06g、20mmol)の無水Et20(75mL)懸濁液に、アルゴン下で7−フェニルヘプタ−6−イノイルクロライド(3)(10mmol、2.21g)の無水Et2O(25mL)溶液を滴下した。原料が転化されたことがTLCで確認されるまで反応液を還流した。ジエチルエーテルをロータリーエバポレータで除去し、2.9gの黄色の粘稠油状物を得た(収率86%)。この油状物を放置すると結晶化した。TLC及びNMRから、純物質であることが確認された。
[1] A. Dray, Biochem. Pharmacol. 1992,44, 611.
[2] M. J. Caterina, M. A. Schumacher, M. Tominaga, T. A.
Rosen, J. D. Levine. D. Julius, Nature 1997,389, 816.
[3] P. Holzer, Pharmacol. Rev. 1991,43, 143.
[4] T. R. LaHahn, R. W. Farmer, Proc. West. Pharmacol Soc.
1983, 26,145
[5] P. M. Gannett, D. L. Nagel, P. J. Reilly, T. Lawson, J. Sharpe, B. Toth, J. Org. Chem. 1988,53, 1064.
[6] Kaga, H. , Miura, M. and Kazuhiko, O. J. Org. Chem. 1989, 54,3477.
[7] K. Kobata, K. Yoshikawa, M. Kohashi, T. Watanabe, Tetrahedron Lett. 1996,37, 2789.
[8] H. Kaga, K. Goto, T. Takahashi, M. Hino, T. Tokuhashi, K. Orito, Tetrahedron 1996,52, 8451.
[9] O. Dasse, A. Mahadevan, L. Han, B. R. Martin, V. Di Marzo, R. K. Razdan, Tetrahedron 2000,56 9195.
[10] M. Miyashita, A. Yoshikoshi, P. A. Grieco, J. Org. Chem.
1977,42, 3772.
[11] K. J. Shea, L. D. Burke, J. Org. Chem. 1988,53, 318.
[11] H. Finkelstein, Chem. Ber. 1910,43, 1528
[12] G. D. Branum, Tetrahedron Lett. 1981,22, 2055.
[13] M. F. Sartori, Chem. Rev. 1951,48, 237.
[14] H. C. Brown, C. P. Garg, K. T. Liu, J. Org. Chem. 1971, 63, 387
Claims (3)
- 請求項2に記載の方法において、
次式:
次式:
次式:
必要に応じて前記カルボン酸を次式:
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
NO20034069A NO20034069L (no) | 2003-09-12 | 2003-09-12 | Fremstilling og bruk av capsaicinderivater |
PCT/NO2004/000270 WO2005025314A1 (en) | 2003-09-12 | 2004-09-10 | Capsaicin derivates and the production and use thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2007505104A JP2007505104A (ja) | 2007-03-08 |
JP4533383B2 true JP4533383B2 (ja) | 2010-09-01 |
Family
ID=29245032
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2006526038A Active JP4533383B2 (ja) | 2003-09-12 | 2004-09-10 | カプサイシン誘導体並びにその製造及び使用 |
Country Status (23)
Country | Link |
---|---|
US (1) | US7446226B2 (ja) |
EP (1) | EP1670310B1 (ja) |
JP (1) | JP4533383B2 (ja) |
KR (1) | KR101116121B1 (ja) |
CN (1) | CN100415095C (ja) |
AT (1) | ATE377947T1 (ja) |
AU (1) | AU2004271873B2 (ja) |
BR (1) | BRPI0414280B1 (ja) |
CY (1) | CY1107884T1 (ja) |
DE (1) | DE602004010164T2 (ja) |
DK (1) | DK1670310T3 (ja) |
EG (1) | EG25674A (ja) |
ES (1) | ES2297477T3 (ja) |
HK (1) | HK1095065A1 (ja) |
HR (1) | HRP20080063T3 (ja) |
IL (1) | IL173981A (ja) |
MY (1) | MY141744A (ja) |
NO (2) | NO20034069L (ja) |
NZ (1) | NZ545537A (ja) |
PL (1) | PL1670310T3 (ja) |
PT (1) | PT1670310E (ja) |
TW (1) | TWI358433B (ja) |
WO (1) | WO2005025314A1 (ja) |
Families Citing this family (32)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8575230B2 (en) | 2007-04-19 | 2013-11-05 | University Of North Texas Health Science Center At Fort Worth | Environment-friendly antifoulants for the prevention of biofouling |
DE102008006430A1 (de) | 2008-01-28 | 2009-08-06 | Florian Galow | Getränkerezeptur |
JP2010059292A (ja) * | 2008-09-02 | 2010-03-18 | Shokichi Inami | 船底塗料並びにその製造方法 |
EP3485881B1 (en) | 2009-07-10 | 2024-03-13 | President and Fellows of Harvard College | Permanently charged sodium and calcium channel blockers as anti-inflammatory agents |
CN102040507B (zh) * | 2009-10-10 | 2013-12-04 | 台州市华南医化有限公司 | 一种7-苯基-6-庚炔酸的制备方法及其反应物5-溴戊酸钠的制备方法 |
US20120027693A1 (en) | 2010-07-27 | 2012-02-02 | Bean Bruce P | Methods and compositions for preventing and relieving muscle cramps and for recovery from neuromuscular irritability and fatigue following exercise |
CN102060689B (zh) * | 2010-12-14 | 2013-05-08 | 台州市华南医化有限公司 | 苯基辣椒碱中间体7-苯基-6-庚炔酸的合成方法 |
WO2012086812A1 (ja) * | 2010-12-22 | 2012-06-28 | 味の素株式会社 | 配糖体化合物 |
BE1019713A3 (fr) * | 2010-12-24 | 2012-10-02 | Axichem Ab | Peinture repulsive a base de derives de capsaicine. |
CN103288665B (zh) * | 2013-06-27 | 2017-02-08 | 上海化学试剂研究所有限公司 | 一种辣椒素的制备方法 |
DK3122715T3 (da) * | 2014-03-27 | 2019-07-15 | Organofuel Sweden Ab | Effektiv syntese af aminer og amider ud fra alkoholer og aldehyder ved anvendelse af kaskadekatalyse |
CN104370985B (zh) * | 2014-09-30 | 2020-04-28 | 上海化学试剂研究所有限公司 | 一种类辣椒素类化合物及其制备方法和应用 |
CN104927585B (zh) * | 2015-07-13 | 2018-10-16 | 上海金泛斯标识有限公司 | 喷绘广告用发光漆 |
MX2018001447A (es) | 2015-08-03 | 2019-02-21 | Harvard College | Bloqueadores de canal de ion cargado y metodos para su uso. |
SG11201802937QA (en) | 2015-10-09 | 2018-05-30 | Axichem Ab | Bird feed and in particular poultry feed, comprising synthetic capsaicinoid derivatives and such feed for prohylactic use or treatment of salmonella infection |
NO341559B1 (en) * | 2016-03-18 | 2017-12-04 | Axichem Ab | Synthetic capsaicinoid derivatives and feed comprising such compounds as growth promotors |
EP3570861A4 (en) | 2017-01-23 | 2020-11-18 | Flex Pharma, Inc. | COMPOSITIONS AND PROCEDURES EFFECTING SPORTING PERFORMANCE |
EP3697402A1 (en) | 2017-10-20 | 2020-08-26 | aXichem AB | Synthetic capsaicin analogues as bioenhancers |
CN108947863B (zh) * | 2018-06-12 | 2021-04-30 | 上海博志研新药物技术有限公司 | 珠卡赛辛及其中间体的制备方法 |
US10786485B1 (en) | 2019-03-11 | 2020-09-29 | Nocion Therapeutics, Inc. | Charged ion channel blockers and methods for use |
JP2022527438A (ja) | 2019-03-11 | 2022-06-02 | ノシオン セラピューティクス,インコーポレイテッド | 荷電したイオンチャンネル遮断薬および使用方法 |
WO2020185881A1 (en) | 2019-03-11 | 2020-09-17 | Nocion Therapeutics, Inc. | Charged ion channel blockers and methods for use |
US10927096B2 (en) | 2019-03-11 | 2021-02-23 | Nocion Therapeutics, Inc. | Ester substituted ion channel blockers and methods for use |
US10780083B1 (en) | 2019-03-11 | 2020-09-22 | Nocion Therapeutics, Inc. | Charged ion channel blockers and methods for use |
WO2021014395A1 (en) * | 2019-07-24 | 2021-01-28 | Dr. Reddy’S Institute Of Life Sciences | Process for the synthesis of deuterated capsaicin, capsaicinoids and synthetic capsaicin analogs |
WO2021091586A1 (en) | 2019-11-06 | 2021-05-14 | Nocion Therapeutics, Inc. | Charged ion channel blockers and methods for use |
JP2023500891A (ja) | 2019-11-06 | 2023-01-11 | ノシオン セラピューティクス,インコーポレイテッド | 荷電したイオンチャンネル遮断薬および使用方法 |
US11332446B2 (en) | 2020-03-11 | 2022-05-17 | Nocion Therapeutics, Inc. | Charged ion channel blockers and methods for use |
NO20200333A1 (en) * | 2020-03-20 | 2021-03-29 | Axichem As | Synthesis of capsaicin derivatives |
NO346665B1 (en) * | 2020-11-17 | 2022-11-21 | Axichem Ab | Capsaicyns in the treatment of leaky gut |
NO346587B1 (en) * | 2021-06-02 | 2022-10-17 | Axichem Ab | Capsaicin derivatives in the treatment of idiopathic pulmonary fibrosis |
NO20220225A1 (en) | 2022-02-18 | 2023-08-21 | Axichem Ab | Bioenhancers |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH04208207A (ja) * | 1990-09-14 | 1992-07-29 | Nippon Kayaku Co Ltd | 白蟻防除剤 |
JPH069308A (ja) * | 1992-06-19 | 1994-01-18 | Nippon Kayaku Co Ltd | 合成カプサイシン類及びそのマイクロカプセル剤の同一浴製造法 |
JP2716329B2 (ja) * | 1992-09-03 | 1998-02-18 | 日本化薬株式会社 | 熱可塑性樹脂組成物用動物咬害防止マスターバッチ及びその製造方法 |
US5629045A (en) * | 1992-09-17 | 1997-05-13 | Richard L. Veech | Biodegradable nosiogenic agents for control of non-vertebrate pests |
US5397385A (en) * | 1994-03-28 | 1995-03-14 | Watts; James L. | Anti-fouling coating composition containing capsaicin |
JPH09100202A (ja) * | 1995-10-03 | 1997-04-15 | Meiji Milk Prod Co Ltd | 抗生物剤 |
-
2003
- 2003-09-12 NO NO20034069A patent/NO20034069L/no not_active Application Discontinuation
-
2004
- 2004-09-03 TW TW093126656A patent/TWI358433B/zh active
- 2004-09-08 MY MYPI20043640A patent/MY141744A/en unknown
- 2004-09-10 CN CNB2004800260925A patent/CN100415095C/zh active Active
- 2004-09-10 DK DK04775054T patent/DK1670310T3/da active
- 2004-09-10 KR KR1020067005093A patent/KR101116121B1/ko active IP Right Grant
- 2004-09-10 NZ NZ545537A patent/NZ545537A/en unknown
- 2004-09-10 ES ES04775054T patent/ES2297477T3/es active Active
- 2004-09-10 WO PCT/NO2004/000270 patent/WO2005025314A1/en active IP Right Grant
- 2004-09-10 PL PL04775054T patent/PL1670310T3/pl unknown
- 2004-09-10 BR BRPI0414280-2A patent/BRPI0414280B1/pt active IP Right Grant
- 2004-09-10 JP JP2006526038A patent/JP4533383B2/ja active Active
- 2004-09-10 AT AT04775054T patent/ATE377947T1/de active
- 2004-09-10 EP EP04775054A patent/EP1670310B1/en active Active
- 2004-09-10 AU AU2004271873A patent/AU2004271873B2/en active Active
- 2004-09-10 PT PT04775054T patent/PT1670310E/pt unknown
- 2004-09-10 US US10/571,658 patent/US7446226B2/en active Active
- 2004-09-10 DE DE602004010164T patent/DE602004010164T2/de active Active
-
2006
- 2006-02-21 NO NO20060834A patent/NO334592B1/no unknown
- 2006-02-27 IL IL173981A patent/IL173981A/en active IP Right Grant
- 2006-03-08 EG EGNA2006000227 patent/EG25674A/xx active
-
2007
- 2007-03-05 HK HK07102406.7A patent/HK1095065A1/xx unknown
-
2008
- 2008-02-11 HR HR20080063T patent/HRP20080063T3/xx unknown
- 2008-02-13 CY CY20081100165T patent/CY1107884T1/el unknown
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP4533383B2 (ja) | カプサイシン誘導体並びにその製造及び使用 | |
KR20060136361A (ko) | 캡사이신 유도체, 및 그 제조방법 및 용도 | |
US20080095737A1 (en) | Non-toxic coating composition, methods of use thereof and articles protected from attachment of biofouling organisms | |
Feng et al. | Synthesis, antibacterial activity, and application in the antifouling marine coatings of novel acylamino compounds containing gramine groups | |
US20160311788A1 (en) | Antifouling Compounds And Use Thereof | |
Escobar et al. | Alkyl 2-furoates obtained by green chemistry procedures as suitable new antifoulants for marine protective coatings | |
US8177896B2 (en) | Antifouling furan-2-one derivatives | |
AU2001275527A1 (en) | Non-toxic coating composition, methods of use thereof and articles protected from attachment of biofouling organisms | |
Inoue et al. | Isocyanides Derived from α, α‐Disubstituted Amino Acids: Synthesis and Antifouling Activity Assessment | |
NZ542883A (en) | Non-toxic coating composition, methods of use thereof and articles protected from attachment of biofouling organisms | |
MXPA06002617A (en) | Capsaicin derivates and the production and use thereof | |
EP3309145A1 (en) | Marine periphyton repellent composition | |
US20020022044A1 (en) | Non-toxic coating composition, methods of use thereof and articles protected from attachment of biofouling organisms | |
Petitbois | Antifouling compounds isolated from two Red Sea organisms: a Hyrtios sp. sponge and an Okeania sp. Cyanobacterium | |
JP2023159371A (ja) | 水中付着生物防汚剤 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A529 | Written submission of copy of amendment under article 34 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A529 Effective date: 20060410 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20070418 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090324 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20090624 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20090701 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090723 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20090915 |
|
A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20100114 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100115 |
|
RD02 | Notification of acceptance of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7422 Effective date: 20100119 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20100114 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20100225 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20100316 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100512 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20100608 |
|
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20100611 |
|
R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 Ref document number: 4533383 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130618 Year of fee payment: 3 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |