WO2013111798A1 - セリンラセマーゼ阻害剤 - Google Patents
セリンラセマーゼ阻害剤 Download PDFInfo
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- WO2013111798A1 WO2013111798A1 PCT/JP2013/051385 JP2013051385W WO2013111798A1 WO 2013111798 A1 WO2013111798 A1 WO 2013111798A1 JP 2013051385 W JP2013051385 W JP 2013051385W WO 2013111798 A1 WO2013111798 A1 WO 2013111798A1
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- 0 C*(C*(C)C(NNC(NC(*)=O)=S)=O)** Chemical compound C*(C*(C)C(NNC(NC(*)=O)=S)=O)** 0.000 description 3
- SBNUJBWEKZWGRH-UHFFFAOYSA-N CC(C)(C)OC(NCC(Nc(c(F)ccc1)c1F)=O)=O Chemical compound CC(C)(C)OC(NCC(Nc(c(F)ccc1)c1F)=O)=O SBNUJBWEKZWGRH-UHFFFAOYSA-N 0.000 description 1
- LGUZSRWNCSSMOG-UHFFFAOYSA-N CC(C)(C)OC(NCC(Nc1cccc([N+]([O-])=O)c1)=O)=O Chemical compound CC(C)(C)OC(NCC(Nc1cccc([N+]([O-])=O)c1)=O)=O LGUZSRWNCSSMOG-UHFFFAOYSA-N 0.000 description 1
- BZCKRPHEZOHHBK-UHFFFAOYSA-N COC(COc1ccccc1)=O Chemical compound COC(COc1ccccc1)=O BZCKRPHEZOHHBK-UHFFFAOYSA-N 0.000 description 1
- KTECLDDPOWTCNQ-UHFFFAOYSA-N COc(cc1)ccc1S(Nc(cccc1)c1NC(Nc(cc1)cc(Cl)c1Cl)=O)(=O)=O Chemical compound COc(cc1)ccc1S(Nc(cccc1)c1NC(Nc(cc1)cc(Cl)c1Cl)=O)(=O)=O KTECLDDPOWTCNQ-UHFFFAOYSA-N 0.000 description 1
- OUNSTZOJBOXBPS-UHFFFAOYSA-N Cc(cc1)ccc1S(NCC(Nc1cc(Br)ccc1)=O)(=O)=O Chemical compound Cc(cc1)ccc1S(NCC(Nc1cc(Br)ccc1)=O)(=O)=O OUNSTZOJBOXBPS-UHFFFAOYSA-N 0.000 description 1
- JTAUOSVDVCIJQN-UHFFFAOYSA-N Cc(cc1)ccc1S(NCCNC(Nc(c(Cl)c1)ccc1Br)=O)(=O)=O Chemical compound Cc(cc1)ccc1S(NCCNC(Nc(c(Cl)c1)ccc1Br)=O)(=O)=O JTAUOSVDVCIJQN-UHFFFAOYSA-N 0.000 description 1
- WBSSCSNXZKLJRV-UHFFFAOYSA-N Cc1cc(OC)ccc1NC(CNCCOc(cc1)ccc1Br)=O Chemical compound Cc1cc(OC)ccc1NC(CNCCOc(cc1)ccc1Br)=O WBSSCSNXZKLJRV-UHFFFAOYSA-N 0.000 description 1
- RGPXNKJLTMCWCC-UHFFFAOYSA-N Cc1ccc(CNC(CNS(c2ccc(C)cc2)(=O)=O)O)cc1 Chemical compound Cc1ccc(CNC(CNS(c2ccc(C)cc2)(=O)=O)O)cc1 RGPXNKJLTMCWCC-UHFFFAOYSA-N 0.000 description 1
- KTQUTKMDIMWOGM-ZZXKWVIFSA-N O=C(/C=C/c(cc1)ccc1F)N=C=S Chemical compound O=C(/C=C/c(cc1)ccc1F)N=C=S KTQUTKMDIMWOGM-ZZXKWVIFSA-N 0.000 description 1
- WHYZPGNYHOESOY-ONEGZZNKSA-N O=C(/C=C/c1cc(Br)cc(Br)c1)NC(NNC(c1ccc[s]1)=O)=S Chemical compound O=C(/C=C/c1cc(Br)cc(Br)c1)NC(NNC(c1ccc[s]1)=O)=S WHYZPGNYHOESOY-ONEGZZNKSA-N 0.000 description 1
- VRVIIPKDEWXBKZ-UHFFFAOYSA-N O=C(CNC(COc(cc1)ccc1Br)=O)NCc(ccc(Br)c1)c1F Chemical compound O=C(CNC(COc(cc1)ccc1Br)=O)NCc(ccc(Br)c1)c1F VRVIIPKDEWXBKZ-UHFFFAOYSA-N 0.000 description 1
- AYETZTKNSIPSPE-UHFFFAOYSA-N O=C(CNC(COc(cc1)ccc1Br)=O)NCc1ccccc1 Chemical compound O=C(CNC(COc(cc1)ccc1Br)=O)NCc1ccccc1 AYETZTKNSIPSPE-UHFFFAOYSA-N 0.000 description 1
- FTSWKUBFMQPZBC-UHFFFAOYSA-N O=C(CNC(COc(cc1)ccc1Br)=O)Nc1cccc(Cl)c1 Chemical compound O=C(CNC(COc(cc1)ccc1Br)=O)Nc1cccc(Cl)c1 FTSWKUBFMQPZBC-UHFFFAOYSA-N 0.000 description 1
- NPWZXLQPERORHA-UHFFFAOYSA-N O=C(CNC(COc(cc1)ccc1F)=O)Nc(cc1)ccc1Br Chemical compound O=C(CNC(COc(cc1)ccc1F)=O)Nc(cc1)ccc1Br NPWZXLQPERORHA-UHFFFAOYSA-N 0.000 description 1
- VCTDAFFVAHRKNH-UHFFFAOYSA-N O=C(CNS(c(cc1)ccc1Cl)(=O)=O)Nc1cccc(Br)c1 Chemical compound O=C(CNS(c(cc1)ccc1Cl)(=O)=O)Nc1cccc(Br)c1 VCTDAFFVAHRKNH-UHFFFAOYSA-N 0.000 description 1
- YGFXFSNBURLVIH-UHFFFAOYSA-N O=C(CNS(c(cc1)ccc1F)(=O)=O)Nc(cccc1)c1Br Chemical compound O=C(CNS(c(cc1)ccc1F)(=O)=O)Nc(cccc1)c1Br YGFXFSNBURLVIH-UHFFFAOYSA-N 0.000 description 1
- YPOCGFLBPITFQR-VMPITWQZSA-N [O-][N+](c1ccc(/C=C/C(NC(NNC(Cc2ccc[s]2)=O)=S)=O)cc1)=O Chemical compound [O-][N+](c1ccc(/C=C/C(NC(NNC(Cc2ccc[s]2)=O)=S)=O)cc1)=O YPOCGFLBPITFQR-VMPITWQZSA-N 0.000 description 1
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C337/00—Derivatives of thiocarbonic acids containing functional groups covered by groups C07C333/00 or C07C335/00 in which at least one nitrogen atom of these functional groups is further bound to another nitrogen atom not being part of a nitro or nitroso group
- C07C337/06—Compounds containing any of the groups, e.g. thiosemicarbazides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
- C07C237/22—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/12—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing rings
- C07C311/13—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing rings the carbon skeleton containing six-membered aromatic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
- C07C311/19—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/21—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
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- C—CHEMISTRY; METALLURGY
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/22—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms
- C07C311/29—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/50—Compounds containing any of the groups, X being a hetero atom, Y being any atom
- C07C311/52—Y being a hetero atom
- C07C311/54—Y being a hetero atom either X or Y, but not both, being nitrogen atoms, e.g. N-sulfonylurea
- C07C311/57—Y being a hetero atom either X or Y, but not both, being nitrogen atoms, e.g. N-sulfonylurea having sulfur atoms of the sulfonylurea groups bound to carbon atoms of six-membered aromatic rings
- C07C311/58—Y being a hetero atom either X or Y, but not both, being nitrogen atoms, e.g. N-sulfonylurea having sulfur atoms of the sulfonylurea groups bound to carbon atoms of six-membered aromatic rings having nitrogen atoms of the sulfonylurea groups bound to hydrogen atoms or to acyclic carbon atoms
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C327/00—Thiocarboxylic acids
- C07C327/38—Amides of thiocarboxylic acids
- C07C327/40—Amides of thiocarboxylic acids having carbon atoms of thiocarboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C327/42—Amides of thiocarboxylic acids having carbon atoms of thiocarboxamide groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of a saturated carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C335/00—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C335/04—Derivatives of thiourea
- C07C335/06—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to acyclic carbon atoms
- C07C335/08—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to acyclic carbon atoms of a saturated carbon skeleton
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C335/00—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C335/04—Derivatives of thiourea
- C07C335/16—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C335/00—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C335/04—Derivatives of thiourea
- C07C335/16—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C335/18—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by singly-bound oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Definitions
- the present invention relates to a non-peptide amide derivative exhibiting serine racemase inhibitory activity.
- NMDA N-methyl-D-aspartate type glutamate receptor
- NMDAR N-methyl-D-aspartate type glutamate receptor
- SR serine racemase
- Dipeptides have a narrow effective concentration range showing an inhibitory effect and have been reported to be cytotoxic, and are not highly specific.
- the object of the present invention is to develop new SR inhibitors with sufficient activity and specificity.
- Another object of the present invention is to develop new therapeutic drug candidates for neurodegenerative diseases and hyperexcited brain pathologies.
- the present inventors Based on the three-dimensional structure information of SR, the present inventors organically synthesize new low molecular weight compounds from the structure information of candidate lead compounds of SR inhibitors found by in silico screening, and evaluate the effects on SR.
- the present invention was completed by finding a compound having an excellent SR inhibitory activity.
- the present invention will be described in detail.
- a halogen atom is a fluorine atom, a chlorine atom, a bromine atom or an iodine atom
- an alkyl group is a linear or branched group such as a methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl and hexyl group the chain C 1-12 alkyl group
- lower alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert- butyl, pentyl and hexyl groups linear or branched C 1-
- a cycloalkyl group is a C 3-8 cycloalkyl group such as cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl
- the hydroxyl protecting group includes all groups that can be used as protecting groups for ordinary hydroxyl groups, such as benzyloxycarbonyl, 4-nitrobenzyloxycarbonyl, 4-bromobenzyloxycarbonyl, 4-methoxybenzyloxycarbonyl, 3,4-dimethoxybenzyloxycarbonyl, methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, 1,1-dimethylpropoxycarbonyl, isopropoxycarbonyl, isobutyloxycarbonyl, diphenylmethoxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 2,2,2-tribromoethoxycarbonyl, 2- (trimethylsilyl) ethoxycarbonyl, 2- (phenylsulfonyl) ethoxycarbonyl, 2- (triphenylphosphoni) ) Ethoxycarbonyl, 2-furfuryloxycarbonyl, 1-adamantyloxycarbonyl, vinyl
- the present invention provides a non-peptidic amide derivative selected from a compound group represented by the following general formula [MM_1], general formula [DR_1], general formula [DR'_1], general formula [LW_1], and general formula [ED_1]. It is a serine racemase inhibitor with one or more active ingredients.
- R 1m represents one or more atoms or substituents selected from a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group and an optionally protected hydroxyl group; R 2m may be substituted.
- Xm represents an oxygen atom or a sulfur atom, respectively.
- R 1d represents one or more atoms or substituents selected from a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group and an optionally protected hydroxyl group; R 2d may be substituted.
- Xd represents an oxygen atom or an imino group, and
- nd represents 0 or 1, respectively.
- R1 d ' represents one or more atoms or substituents selected from a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group and an optionally protected hydroxyl group; R2 d' is substituted An optionally substituted aryl, aralkyl or arylacetamide group; X d ′ represents an oxygen atom or an imino group, respectively.
- R 1w represents an optionally substituted styryl, benzyl or cyclohexylmethyl group
- R 2w represents an optionally substituted aryl, oxygen atom or sulfur atom as a ring atom.
- Nw represents 0, 1, or 2, respectively.
- R 1e is the same or different and represents one or more atoms or substituents selected from a hydrogen atom, a halogen atom, an alkyl group, and an alkoxy group;
- R 2e represents an optionally substituted phenyl or tolyl Sulfonyl;
- Ae represents an alkylene or phenylene group, respectively.
- the present invention is a novel non-peptide amide derivative represented by the following general formula having serine racemase inhibitory activity.
- R 1m represents one or more atoms or substituents selected from a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group and an optionally protected hydroxyl group
- R 2Am represents a halogen atom, an alkyl group
- An aryl, aralkyl or cycloalkyl group optionally substituted with 1 to 2 atoms or a substituent selected from an alkoxy group, a nitro group and an optionally protected hydroxyl group
- X m represents an oxygen atom or Each represents a sulfur atom.
- R 1d represents one or more atoms or substituents selected from a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group and an optionally protected hydroxyl group; R 2d may be substituted. A good aryl, aralkyl or arylacetamido group; Xd represents an oxygen atom or an imino group, respectively.
- R 1d represents one or more atoms or substituents selected from a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group and an optionally protected hydroxyl group; R 2ad may be substituted. A good benzyl group or an optionally substituted arylacetamido group is shown respectively.
- R 1d ′ represents one or more atoms or substituents selected from a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, and an optionally protected hydroxyl group
- R 2d ′ represents a substituted group.
- X d ′ represents an oxygen atom or an imino group, respectively.
- R 13w is a halogen atom
- R 12w, R 14w, R 15w and R 16w are the same or different, a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, one or more selected from a nitro group
- R 2bw represents a heterocyclic group containing an optionally substituted aryl, oxygen atom or sulfur atom as a ring atom, respectively.
- R 2cw represents an optionally substituted oxygen atom or a heterocyclic group containing an oxygen atom as a ring atom
- the substituents R 12w to R1 6w represent the following combinations, respectively.
- R 12w, R 14w and R 16w is a hydrogen atom
- R 13w and R 15 w is a halogen atom
- R 13w, R 14w and R 15 w represent a hydrogen atom
- the R 12w and R 16w an alkoxy group " N-[(acyl) hydrazinocarbothionyl] -acetamide derivatives represented by:
- R 1aw represents one or more atoms or substituents selected from a halogen atom, an alkyl group, an alkoxy group, a nitro group and an optionally protected hydroxyl group; the substituents of R 22w to R 26w are The following combinations are shown respectively.
- R 24w is a halogen atom
- R 22w , R 23w , R 25w and R 26w are hydrogen atoms
- R 23w is an alkyl group
- R 22w , R 24w , R 25w and R 26w are hydrogen atoms
- R 22w and R 26w are halogen atoms
- R 23w , R 24w and R 26w are hydrogen atoms
- R 23w and R 25w are halogen atoms
- R 22w , R 24w and R 26w are hydrogen atoms " N-[(acyl) hydrazinocarbothionyl] -acetamide derivatives represented by:
- R 2w represents an optionally substituted aryl, oxygen atom or heterocyclic group containing an oxygen atom as a ring atom; nw represents 0, 1, or 2, respectively.”
- R 11e represents a hydrogen atom, an alkyl group or an alkoxy group
- R 21e represents a hydrogen atom, a halogen atom or an alkyl group
- R 22e represents a hydrogen atom or a halogen atom
- R 23e represents a hydrogen atom or A halogen atom
- R 24e represents a hydrogen atom, an alkyl group or an alkoxy group
- X e represents an oxygen atom or a sulfur atom
- ne represents an integer of 2 or 3, respectively.
- R 11e is an alkyl group
- R 21e and R 23e are halogen atoms
- R 22e and R 24e are hydrogen
- X e is an oxygen atom
- ne is 2.
- R 11e represents a hydrogen atom, an alkyl group or an alkoxy group
- R 25e and R 26e are the same or different and represent a hydrogen atom or an alkyl group
- ne represents an integer of 2 or 3, respectively.
- R 11e represents a hydrogen atom, an alkyl group or an alkoxy group
- R 22e and R 23e are the same or different and each represents a hydrogen atom or an alkyl group.
- non-peptidic amide derivative represented by the above general formula when isomers (for example, optical isomers, geometric isomers, tautomers, etc.) exist, the present invention converts all of these isomers. And includes hydrates, solvates and all crystalline forms.
- the non-peptide amide derivative represented by the general formula may form a salt, and examples of the salt include a salt at a generally known imino group or hydroxyl group.
- salts with alkali metals such as sodium and potassium can be mentioned as salts of the DR compound and the ED compound.
- Preferred salts include pharmacologically acceptable salts.
- examples of preferable compounds having serine racemase inhibitory activity include the following compounds.
- ⁇ MM compound> “wherein R 1am represents a hydrogen atom, a halogen atom, an alkoxy group, an optionally protected hydroxyl group; R 1bm represents a hydrogen atom or an alkyl group; R 2am represents an optionally substituted aryl group Or a cycloalkyl group; X m represents an oxygen atom or a sulfur atom; nm represents 0 or the integer 1;
- a phenoxy- (N-substituted carbamoylmethyl) -acetamide derivative represented by:
- More preferable compounds include, for example, the following compounds. “Wherein R 1am represents a hydrogen atom, a halogen atom, an alkoxy group, an optionally protected hydroxyl group; R 1bm represents a hydrogen atom or an alkyl group; R 2bm represents a hydrogen atom, a halogen atom, an alkyl group; , One or more atoms or substituents selected from a nitro group and a hydroxy group, respectively.
- a phenoxy- (N-substituted carbamoylmethyl) -acetamide derivative represented by:
- R 1ad represents one or more atoms or substituents selected from a hydrogen atom, a halogen atom, an alkyl group and an alkoxy group
- R 2bd represents an optionally substituted aralkyl group
- nd represents 0 Or 1 respectively.
- R 1ad represents one or more atoms or substituents selected from a hydrogen atom, a halogen atom, an alkyl group and an alkoxy group
- R 2cd represents an aryl or aralkyl group which may be substituted, respectively.
- Show. N- (substituted) -2- (substituted sulfamoylamino) -acetamide derivatives represented by:
- R 1ad represents one or more atoms or substituents selected from a hydrogen atom, a halogen atom, an alkyl group and an alkoxy group
- R 2ad represents a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group and a protected group.
- One or more atoms or substituents each selected from an optionally substituted hydroxyl group are shown.
- R 1d ′ represents one or more atoms or substituents selected from a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, and an optionally protected hydroxyl group
- R 2d ′ represents a substituted group.
- X d ′ represents an oxygen atom or an imino group, respectively.
- R 1aw represents one or more atoms or substituents selected from a halogen atom, an alkyl group, an alkoxy group, a nitro group and an optionally protected hydroxyl group; R 2w and R 2aw are substituted.
- More preferable compounds include, for example, the following compounds.
- R 13w is a halogen atom
- R 12w, R 14w, R 15w and R 16w are the same or different, a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, one or more selected from a nitro group
- R 2bw represents a heterocyclic group containing an optionally substituted aryl, oxygen atom or sulfur atom as a ring atom, respectively.
- R 12w, R 14w and R 16w is a hydrogen atom
- R 13w and R 15 w is a halogen atom
- R 13w, R 14w and R 15 w represent a hydrogen atom
- the R 12w and R 16w an alkoxy group " N-[(acyl) hydrazinocarbothionyl] -acetamide derivatives represented by:
- R 12w to R 16w represent the following combinations. (1) R 12w, R 14w and R 16w is a hydrogen atom; R 13w and R 15 w is a halogen atom (2) R 13w, R 14w and R 15 w represent a hydrogen atom; the R 12w and R 16w, an alkoxy group " N-[(acyl) hydrazinocarbothionyl] -acetamide derivatives represented by:
- R 1aw represents one or more atoms or substituents selected from a halogen atom, an alkyl group, an alkoxy group, a nitro group and an optionally protected hydroxyl group; the substituents of R 22w to R 26w are The following combinations are shown respectively.
- R 24w is a halogen atom
- R 22w , R 23w , R 25w and R 26w are hydrogen atoms
- R 23w is an alkyl group
- R 22w , R 24w , R 25w and R 26w are hydrogen atoms
- R 22w and R 26w are halogen atoms
- R 23w , R 24w and R 26w are hydrogen atoms
- R 23w and R 25w are halogen atoms
- R 22w , R 24w and R 26w are hydrogen atoms " N-[(acyl) hydrazinocarbothionyl] -acetamide derivatives represented by:
- R 1e is the same or different and represents one or more atoms or substituents selected from a hydrogen atom, a halogen atom, an alkyl group, and an alkoxy group;
- R 2e represents an optionally substituted phenyl or tolyl Sulfonyl ;
- R 2ae represents an optionally substituted phenyl;
- ne represents an integer of 2 or 3, respectively.
- More preferable compounds include, for example, the following compounds. “Wherein R 11e represents a hydrogen atom, an alkyl group or an alkoxy group; R 21e represents a hydrogen atom, a halogen atom or an alkyl group; R 22e represents a hydrogen atom or a halogen atom; R 23e represents a hydrogen atom or A halogen atom; R 24e represents a hydrogen atom, an alkyl group or an alkoxy group; X e represents an oxygen atom or a sulfur atom; ne represents an integer of 2 or 3, respectively.
- R 11e is an alkyl group
- R 21e and R 23e are halogen atoms
- R 22e and R 24e are hydrogen atoms
- X e is an oxygen atom
- ne is 2.
- R 11e represents a hydrogen atom, an alkyl group or an alkoxy group
- R 25e and R 25e are the same or different and represent a hydrogen atom or an alkyl group
- ne represents an integer of 2 or 3, respectively.
- R 11e represents a hydrogen atom, an alkyl group or an alkoxy group
- R 22e and R 23e are the same or different and each represents a hydrogen atom or a halogen atom.
- the non-peptide amide derivative of the present invention can be produced, for example, by the following method. Production method 1 ⁇ MM compound>
- R 1m represents one or more atoms or substituents selected from a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group and an optionally protected hydroxyl group; R 2m may be substituted.
- Xm represents an oxygen atom or a sulfur atom, respectively.
- a compound of general formula [MM_1] can be produced by reacting a compound of general formula [MM_3] with a compound of general formula [MM_4] in the presence of a condensing agent.
- the solvent used in this reaction is not particularly limited as long as it does not adversely influence the reaction, and examples thereof include halogenated carbons such as methylene chloride and chloroform; ethers such as tetrahydrofuran and amides such as N, N-dimethylformamide. It is done.
- the condensing agent used in this reaction include carbonyldiimidazole and 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide (EDC).
- EDC 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide
- additives of 1-hydroxybenzotriazole (HOBt) and 3,4-dihydro-3-hydroxy-4-oxo-1,2,3-benzotriazine (HOOBt) may be used at the same time.
- the amount of the condensing agent used may be equimolar or more, preferably 1 to 10 times the molar amount of the compound of the general formula [3]. This reaction is usually carried out at 0 to 200 ° C., preferably 10 to 150 ° C., for 10 minutes to 24 hours.
- the compound of the general formula [MM_3] can be produced by a method known per se.
- the following documents may be referred to. ⁇ Synth. Commun. 2004, 34, 377-382. ⁇ Lett. Org. Chem. 2011, 8, 234-241. ⁇ Org. Lett. 2010, 12, 4571-4575. ⁇ US Pat. Appl. Publ., 20070141113, 21 Jun 2007 ⁇ Faming Zhuanli Shenqing Gongkai Shuomingshu, 101314576, 03 Dec 2008 ⁇ J. Am. Chem. Soc. 2007, 129, 3981-3929.
- the compound of the general formula [MM_4] can be produced by a method known per se.
- the following documents may be referred to. ⁇ Eur. J. Org. Chem. 2008, 23, 3976-3983. Eur. J. Med. Chem. 1996, 31, 497-505. ⁇ PCT Int. Appl. (2000), WO 2000071507 A2 20001130. ⁇ J. Org. Chem. 2011, 76, 9278-9293. ⁇ J. Med. Chem. 2009, 52, 5005-5008.
- ⁇ Org. Lett. 2010, 12, 2718-2721. ⁇ PCT Int. Appl. (2010), WO 2010067067 A1 20100617.
- the compound of the general formula [MM_1] thus obtained can be isolated and purified by usual methods such as extraction, crystallization, distillation and column chromatography.
- R 1d represents one or more atoms or substituents selected from a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group and an optionally protected hydroxyl group; R 2d may be substituted.
- X d represents an oxygen atom or imino group;
- nd represents 0 or 1, respectively.
- the solvent used in this reaction is not particularly limited as long as it does not adversely affect the reaction, and examples thereof include halogenated carbons such as methylene chloride and chloroform; ethers such as tetrahydrofuran and the like.
- Examples of the base used in this reaction include organic bases such as diethylamine, triethylamine, and N, N-dimethyl-4-aminopyridine.
- the amount of the base used may be 0.1 to 2 moles compared to the compound of the general formula [3]. This reaction is usually carried out at 0 to 200 ° C., preferably 10 to 150 ° C., for 10 minutes to 24 hours.
- the compound of the general formula [DR_2] or the general formula [DR′_2] can be produced by a method known per se.
- the following documents may be referred to. ⁇ J. Med. Chem., 2011, 54, 2738-2744. ACS Chem. Neurosci., 2010, 1, 155-164. ⁇ US2008 / 0269280 A1
- the compound of the general formula [DR_3] can be produced by a method known per se.
- the following documents may be referred to. ⁇ Tetrahedron Lett., 2011, 52, 2579-2582.
- R 1w represents an optionally substituted styryl, benzyl or cyclohexylmethyl group
- R 2w represents an optionally substituted aryl, oxygen atom or sulfur atom as a ring atom.
- Nw represents 0, 1, or 2, respectively.
- the compound of the general formula [LW_1] can be produced by reacting the compound of the general formula [LW_2] and the compound of the general formula [LW_3].
- the solvent used in this reaction is not particularly limited as long as it does not adversely affect the reaction, and examples thereof include halogenated carbons such as methylene chloride and chloroform; ethers such as tetrahydrofuran and the like.
- This reaction is usually carried out at 0 to 200 ° C., preferably 10 to 150 ° C., for 10 minutes to 24 hours.
- the compound of the general formula [LW_2] and its starting compound can be produced by a method known per se.
- the following documents may be referred to. Tetrahedron, 2011, 67, 8120-8130. Bioorg. Med. Chem., 2004, 13, 433-441. Synthesis, 2008, 279-285. J. Org. Chem., 2008, 73, 5766-5775. Org. Biomol. Chem., 2009, 7, 4062-4066. Chem. Eur. J., 2000, 6, 3386-3390. Synth. Commun., 1980, 10, 37-42. Synth. Commun., 2002, 32, 195-201. J. Med. Chem., 1993, 36, 2381-9. J. Org.
- the compound of the general formula [LW — 3] can be produced by a method known per se.
- carboxylic acid ester may be reacted with hydrazine monohydrate.
- R 2w represents an optionally substituted aryl, oxygen atom or sulfur atom as a ring atom
- R ′ represents an alkyl group
- nw represents 0, 1, or 2 , Respectively.
- the compound of the general formula [LW_1] thus obtained can be isolated and purified by ordinary methods such as extraction, crystallization, distillation and column chromatography.
- Production method 4 ⁇ ED compound> "Wherein R 1e is the same or different and represents one or more atoms or substituents selected from a hydrogen atom, a halogen atom, an alkyl group, and an alkoxy group; R 2e represents an optionally substituted phenyl or tolyl Sulfonyl; Ae represents an alkylene or phenylene group, respectively. "
- the compound of the general formula [ED_1] can be produced by reacting the compound of the general formula [ED_2] with the compound of the general formula [ED_3].
- the solvent used in this reaction is not particularly limited as long as it does not adversely affect the reaction, and examples thereof include halogenated carbons such as methylene chloride and chloroform; ethers such as tetrahydrofuran and the like.
- This reaction is usually carried out at 0 to 200 ° C., preferably 10 to 100 ° C., for 10 minutes to 24 hours.
- the general formula [ED_2] compound and its starting compound can be produced by a method known per se.
- a general formula “ED_4” benzenesulfonyl chloride and a diamine of the general formula “ED_5” are prepared under known conditions as follows. It can manufacture by making it react under.
- R 1e is the same or different and represents one or more atoms or substituents selected from a hydrogen atom, a halogen atom, an alkyl group and an alkoxy group; A e represents an alkylene or phenylene group, respectively.
- the compound of the general formula [ED_1] thus obtained can be isolated and purified by usual methods such as extraction, crystallization, distillation and column chromatography.
- the compound of the present invention comprises a solvent, a bulking agent, an isotonic agent, a solubilizer, an emulsifier, a suspending agent, a thickener, an absorption accelerator, a gelation / coagulation accelerator, a light stabilizer, a preservative, and an emulsifier.
- a solvent a bulking agent
- an isotonic agent a solubilizer
- the administration method of the said formulation is not specifically limited, It determines suitably according to the form of a formulation, patient's age, sex, other conditions, and the symptom level of a patient.
- the dosage of the active ingredient of the preparation of the present invention is appropriately selected according to the usage, patient age, sex, disease form, other conditions, etc., but usually 0.1 to 500 mg per day for an adult. What is necessary is just to divide and administer from once to several times.
- Test example 1 Method for measuring enzyme activity> The inhibitory effect of the compound on the activity of serine racemase (SR) was determined by the following (1) racemization reaction of L-serine and (2) quantification of produced D-serine.
- Non-peptidic amide derivatives have serine racemase inhibitory activity. Therefore, these compounds can regulate the activity of NMDAR and can be used as new therapeutic agents for neurodegenerative diseases and brain conditions of hyperexcitability.
- methyl bromoacetate (0.10 mL, 1 mmol) and potassium carbonate (207 mg, 1.5 mmol) are sequentially added to a dimethylformamide (3 mL) solution of a phenol compound (1.0 mmol), and the mixture is stirred at 80 ° C. overnight.
- the reaction mixture is then diluted with ethyl acetate (10 mL), filtered through celite, and the solvent is distilled off.
- 1,1-carbonylimidazole (1.38 g, 8.51 mmol) was added to a methylene chloride (10 mL) solution of N-tert-butoxycarbonyl glycine (1.36 g, 7.74 mmol), and 1 at room temperature. After stirring for 2 hours, 2,6-difluoroaniline (0.78 mL, 7.74 ml) is added and stirred overnight at room temperature.
- 1,1-carbonylimidazole (1.38 g, 8.51 mmol) was added to a methylene chloride (10 mL) solution of N- (tert-butoxycarbonyl) glycine (1.36 g, 7.74 mmol) at room temperature. After stirring for 1 hour, add 2,6-difluoroaniline (0.78 mL, 7.74 mmol) and stir at room temperature overnight.
- 1,1-carbonyldiimidazole (357 mg, 2.2 mmol) was added to a solution of N- (tert-butoxycarbonyl) glycine (350 mg, 2.0 mmol) in methylene chloride (5 mL), and the mixture was stirred at room temperature for 1 hour. Thereafter, benzyl alcohol (0.21 mL, 2.0 mmol) was added, and the mixture was stirred overnight at room temperature.
- thionyl chloride (0.15 mL, 2.00 mmol) is added to a solution of cyclohexylacetic acid (142 mg, 1.00 mmol) in benzene (5 mL), and the mixture is heated to reflux overnight. After the solvent is distilled off, methylene chloride (5 mL) is added, and then ammonium thiocyanate (114 mg, 1.50 mmol) and PEG-400 (4 drops) are sequentially added, and the mixture is stirred at room temperature for 2 overnight.
- thionyl chloride (0.29 mL, 4.00 mmol) was added to a solution of 2-thiopheneacetic acid (284 mg, 2.00 mmol) in methylene chloride (5 mL), and the mixture was heated to reflux overnight. After the solvent was distilled off, methylene chloride (5 mL) was newly added, and then thioammonium cyanide (228 mg, 3.00 mmol) and polyethylene glycol (PEG-400; 6 drops) were sequentially added, followed by stirring at room temperature overnight.
- pyridine (0.149 mL, 1.85 mmol) is added to a 3 mL solution of o-phenylenediamine (500 mg, 4.62 mmol) in tetrahydrofuran, and then a tetrahydrofuran solution of toluenesulfonyl chloride (294 mg, 1.54 mmol).
- o-phenylenediamine 500 mg, 4.62 mmol
- tetrahydrofuran solution of toluenesulfonyl chloride (294 mg, 1.54 mmol).
- the organic layer extracted with methylene chloride is washed with 5 mL of saturated brine, dried over sodium sulfate, and filtered.
- Lithium hydroxide monohydrate (52 mg, 1.23 mmol) was added to a methanol / water (3: 1) mixed solution (4 mL) of phenoxyacetic acid methyl ester (102 mg, 0.61 mmol) for 2 hours. Heat to reflux. After distilling off the solvent, a 10% aqueous hydrochloric acid solution is added until the aqueous layer shows acidity, and the mixture is extracted with ethyl acetate. The organic layer is dried over sodium sulfate, filtered, and then the solvent is distilled off to obtain phenoxyacetic acid (92 mg) as a colorless crystalline substance.
- Phenyl isocyanate (0.051 mL, 0.47 mmol) is added to 5 mL of a methylene chloride solution of N- (2-aminoethyl) -4-methylbenzenesulfoamide (100 mg, 0.47 mmol) and stirred overnight at room temperature.
- the non-peptidic amide derivative of the present invention has serine racemase inhibitory activity, and can be used as a drug for preventing or treating pathological conditions associated with excessive activation of NMDAR and neurodegenerative diseases. It can also be used as a research reagent for analyzing the function of serine racemase in the nervous system.
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Abstract
Description
記憶や学習に関わる受容体であると考えられており、アルツハイマー型痴呆の治療薬のターゲットの一つである。
一方、哺乳類脳内にはD-セリンが存在し、内因性コ・アゴニストとしてNMDARの機能制御に関わっている。
D-セリンは、L-セリンからセリンラセマーゼ(SR)により合成される。
SRノックアウト(KO)マウスでは、NMDA誘発の神経変性が軽減する(非特許文献1)、PTZ誘発てんかん発作が軽減することなどが知られている。
従って、SRは神経過剰興奮に伴う病態に対する新たな創薬標的と考えられ、SRの阻害薬に関しては、ジペプチド類等の報告がある(非特許文献2)。
本発明の目的は、十分な活性と特異性のある新規なSR阻害剤を開発することである。
また、本発明の別の目的は、神経変性疾患や過剰興奮の脳病態に対する新たな治療薬候補を開発するものである。
以下、本発明を詳細に説明する。
ハロゲン原子とは、フッ素原子、塩素原子、臭素原子またはヨウ素原子を;アルキル基とは、メチル、エチル、プロピル、イソプロピル、ブチル、イソブチル、tert-ブチル、ペンチルおよびヘキシル基などの直鎖状または分岐鎖状のC1-12アルキル基を;低級アルキル基とは、メチル、エチル、プロピル、イソプロピル、ブチル、イソブチル、tert-ブチル、ペンチルおよびヘキシル基などの直鎖状または分岐鎖状のC1-6アルキル基を;シクロアルキル基とは、シクロプロピル、シクロブチル、シクロペンチルおよびシクロヘキシルなどのC3-8シクロアルキル基を;アリール基とは、フェニル、ナフチル、インダニルおよびインデニル基などを;アルアルキルとは、ベンジル、フェネチル、α-メチルフェネチル、ジフェニルメチル、トリチルなどアリール-低級アルキル基を;アルコキシ基とは、メトキシ、エトキシ、プロポキシ、イソプロポキシ、ブトキシ、イソブトキシ、tert-ブトキシ、ペンチルオキシ、ヘキシルオキシ、ヘプチルオキシおよびオクチルオキシ基などの直鎖状または分岐鎖状のC1-12アルキルオキシ基を;低級アルコキシ基とは、メトキシ、エトキシ、プロポキシ、イソプロポキシ、ブトキシ、イソブトキシ、tert-ブトキシ、ペンチルオキシおよびヘキシルオキシ基などの直鎖状または分岐鎖状のC1-6アルキルオキシ基を、アルキレンとはメチレン、エチレン、プロピレンなど直鎖状または分岐鎖状のC1-6アルキレン基を、それぞれ意味する。
で表されるフェノキシ-(N-置換カルバモイルメチル)-アセトアミド誘導体。
で表されるN-(置換)-2-(置換スルファモイルアミノ)-アセトアミド誘導体。
で表されるN-(置換)-2-(置換スルファモイルアミノ)-アセトアミド誘導体。
で表されるN-[(アシル)ヒドラジノカルボチオニル]-アセトアミド誘導体。
で表されるベンゼンスルホニルアミド誘導体。
で表されるフェノキシ-(N-置換カルバモイルメチル)-アセトアミド誘導体。
で表されるN-(置換)-2-(置換スルファモイルアミノ)-アセトアミド誘導体。
で表されるN-(置換)-2-(置換スルファモイルアミノ)-アセトアミド誘導体。
で表されるN-(置換)-2-(置換スルファモイルアミノ)-アセトアミド誘導体。
で表されるN-[(アシル)ヒドラジノカルボチオニル]-アセトアミド誘導体。
(1)R12w、R14wおよびR16wは、水素原子;R13wおよびR15wは、ハロゲン原子
(2)R13w、R14wおよびR15wは、水素原子;R12wおよびR16wは、アルコキシ基」
で表されるN-[(アシル)ヒドラジノカルボチオニル]-アセトアミド誘導体。
(1)R24wが、ハロゲン原子;R22w、R23w、R25wおよびR26wは、水素原子
(2)R23wが、アルキル基;R22w、R24w、R25wおよびR26wは、水素原子
(3)R22wおよびR26wが、ハロゲン原子;R23w、R24wおよびR26wは、水素原子
(4)R23wおよびR25wが、ハロゲン原子;R22w、R24wおよびR26wは、水素原子」
で表されるN-[(アシル)ヒドラジノカルボチオニル]-アセトアミド誘導体。
で表されるN-[(アシル)ヒドラジノカルボチオニル]-アセトアミド誘導体。
但し、R11eがアルキル基、R21eおよびR23eがハロゲン原子、R22eおよびR24eが水素あ、Xeが酸素原子、neが2である場合を除く」
で表されるベンゼンスルホニルアミド誘導体。
で表されるベンゼンスルホニルアミド誘導体。
また、一般式で表される非ペプチド性のアミド誘導体は、塩を形成していてもよく、それらの塩としては、通常知られているイミノ基またはヒドロキシル基における塩を挙げることができる。
具体的には、例えば、DR化合物およびED化合物の塩として、ナトリウムおよびカリウムなどのアルカリ金属との塩が挙げられる。
好ましい塩としては、薬理学的に許容される塩が挙げられる。
<MM化合物>
で表されるフェノキシ-(N-置換カルバモイルメチル)-アセトアミド誘導体。
で表されるフェノキシ-(N-置換カルバモイルメチル)-アセトアミド誘導体。
で表されるN-(置換)-2-(置換スルファモイルアミノ)-アセトアミド誘導体。
で表されるN-(置換)-2-(置換スルファモイルアミノ)-アセトアミド誘導体。
で表されるN-(置換)-2-(置換スルファモイルアミノ)-アセトアミド誘導体。
さらに好ましい化合物は、例えば、以下の化合物が挙げられる。
で表されるN-[(アシル)ヒドラジノカルボチオニル]-アセトアミド誘導体。
(1)R12w、R14wおよびR16wは、水素原子;R13wおよびR15wは、ハロゲン原子
(2)R13w、R14wおよびR15wは、水素原子;R12wおよびR16wは、アルコキシ基」
で表されるN-[(アシル)ヒドラジノカルボチオニル]-アセトアミド誘導体。
(1)R12w、R14wおよびR16wは、水素原子;R13wおよびR15wは、ハロゲン原子
(2)R13w、R14wおよびR15wは、水素原子;R12wおよびR16wは、アルコキシ基」
で表されるN-[(アシル)ヒドラジノカルボチオニル]-アセトアミド誘導体。
(1)R24wが、ハロゲン原子;R22w、R23w、R25wおよびR26wは、水素原子
(2)R23wが、アルキル基;R22w、R24w、R25wおよびR26wは、水素原子
(3)R22wおよびR26wが、ハロゲン原子;R23w、R24wおよびR26wは、水素原子
(4)R23wおよびR25wが、ハロゲン原子;R22w、R24wおよびR26wは、水素原子」
で表されるN-[(アシル)ヒドラジノカルボチオニル]-アセトアミド誘導体。
で表されるベンゼンスルホニルアミド誘導体。
但し、R11eがアルキル基、R21eおよびR23eがハロゲン原子、R22eおよびR24eが水素原子、Xeが酸素原子、neが2である場合を除く」
で表されるベンゼンスルホニルアミド誘導体。
で表されるベンゼンスルホニルアミド誘導体。
・製造法1<MM化合物>
この反応に用いられる縮合剤としては、例えば、カルボニルジイミダゾール (carbonyldiimidazole)、1-エチル-3-(3-ジメチルアミノプロピル)カルボジイミド(EDC)などが挙げられる。
また、さらに1-ヒドロキシベンゾトリアゾール(HOBt)、 3,4-ジヒドロ-3-ヒドロキシ-4-オキソ-1,2,3-ベンゾトリアジン(HOOBt)の添加剤を同時に用いてもよい。
縮合剤の使用量は、一般式[3]の化合物に対して、等モル以上、好ましくは、1~10倍モルであればよい。
この反応は、通常、0~200℃、好ましくは、10~150℃で、10分~24時間実施すればよい。
・Synth. Commun. 2004, 34, 377-382.
・Lett. Org. Chem. 2011, 8, 234-241.
・Org. Lett. 2010, 12, 4571-4575.
・U.S. Pat. Appl. Publ., 20070141113, 21 Jun 2007
・Faming Zhuanli Shenqing Gongkai Shuomingshu, 101314576, 03 Dec 2008
・J. Am. Chem. Soc. 2007, 129, 3981-3929.
・Eur. J. Org. Chem. 2008, 23, 3976-3983.
・Eur. J. Med. Chem. 1996, 31, 497-505.
・PCT Int. Appl. (2000), WO 2000071507 A2 20001130.
・J. Org. Chem. 2011, 76, 9278-9293.
・J. Med. Chem. 2009, 52, 5005-5008.
・Org. Lett. 2010, 12, 2718-2721.
・PCT Int. Appl. (2010), WO 2010067067 A1 20100617.
・PCT Int. Appl., 2007141473, 13 Dec 2007
また、それらの化合物は、単離せずにそのまま次の反応に用いてもよい。
この反応に用いられる塩基としては、例えば、ジエチルアミン、トリエチルアミン、N,N-ジメチル-4-アミノピリジンなどの有機塩基が挙げられる。
塩基の使用量は、一般式[3]の化合物に対して、0.1~2倍モルであればよい。
この反応は、通常、0~200℃、好ましくは、10~150℃で、10分~24時間実施すればよい。
・J. Med. Chem., 2011, 54, 2738-2744.
・ACS Chem. Neurosci., 2010, 1, 155-164.
・US2008/0269280 A1
・Tetrahedron Lett., 2011, 52, 2579-2582.
また、それらの化合物は、単離せずにそのまま次の反応に用いてもよい。
・製造法3<LW化合物>
この反応は、通常、0~200℃、好ましくは、10~150℃で、10分~24時間実施すればよい。
Tetrahedron, 2011, 67, 8120-8130.
Bioorg. Med. Chem., 2004, 13, 433-441.
Synthesis, 2008, 279-285.
J. Org. Chem., 2008, 73, 5766-5775.
Org. Biomol. Chem., 2009, 7, 4062-4066.
Chem. Eur. J., 2000, 6, 3386-3390.
Synth. Commun., 1980, 10, 37-42.
Synth. Commun., 2002, 32, 195-201.
J. Med. Chem., 1993, 36, 2381-9.
J. Org. Chem., 1995, 60, 1981-4.
J. Org. Chem., 1999, 64, 3975-3978.
WO 2004046122 A2
WO 2001092239 A1
Bioorg. Med. Chem. Lett., 2011, 21, 1102-1104.)
Chem. Pep. Chem. Zvesti, 1974, 28, 693-6.
Chem. Pep. Chem. Zvesti, 1969, 23, 173-80.
J. Med. Chem., 2006, 49, 2186-2192.
Bioorg. Med. Chem. Lett., 2008, 18, 1945-1951.
WO 2009125597 A1
WO 2007054831 A2
また、それらの化合物は、単離せずにそのまま次の反応に用いてもよい。
この反応は、通常、0~200℃、好ましくは、10~100℃で、10分~24時間実施すればよい。
また、それらの化合物は、単離せずにそのまま次の反応に用いてもよい。
本発明製剤の有効成分の投与量は、用法、患者の年齢、性別、疾患の形態、その他の条件などに応じて適宜選択されるが、通常成人に対して、1日0.1~500mgを1回から数回に分割して投与すればよい。
試験例1
<酵素活性測定方法>
セリンラセマーゼ(SR)の活性に対する化合物の阻害効果は、以下の(1)L-セリンのラセミ化反応と、(2)生産されるD-セリンの定量により求めた。
Strisovskyらの方法 (Biochemistry, 44:13091-13100, 2005.)に従い、大腸菌で発現させ精製したリコンビナントSR (3.7μg)を、100mM HEPES (pH 8.0), 1mM MgCl2, 10μM PLP, 1mM ATP, 20mM L-セリン, 5mM DTT, ならびにDMSOに溶解した化合物(1~0.01mM)を含む反応液125μL中、37℃で8時間以上反応させた。
Itoらの方法 ( Analytical Biochemistry, 371: 167-172, 2007.)に従って行った。
(1)の反応液25μLに25μLの100mM HEPES (pH 8.0), 20μM PLP, 2μg リコンビナントD-セリンデヒドラターゼ1 (Dsd1)を含む溶液を加え、30℃で30分間反応させた。
次いでD-セリンからDsd1によって生産されるピルビン酸を比色反応によって測定するため、反応溶液50μLに50μLの0.05% DNP/2M HClを加え、30℃で5分間反応させた後、100μLエタノールを加え、次いで125μLの10M NaOHを加え、よく混和して室温で10 分間反応させ、515nmの波長の吸光度を分光光度計で測定した。
結果を表1および表2に示す。
なお、表1~表8の括弧内の数値は対照のマロン酸である。
なお、これらは本発明を何ら限定するものではない。
また、化学構造式中の略号は以下のとおりである。
Me:メチル、Ph:フェニル、Bn:ベンジル、Boc:ブトキシカルボニル
その後反応液を酢酸エチル(10mL)で希釈し、セライトろ過し、溶媒を留去する。
得られた残渣をシリカゲルカラムクロマトグラフィー(15g,ヘキサン:アセトン=50:1~40:1)にて精製すれば、メチルエステル体を得る。
参考文献:Faming Zhuanli Shenqing Gongkai Shuomingshu, 101314576, 03 Dec 2008
溶媒を留去し、得られた残渣をシリカゲルカラムクロマトグラフィー(20g,ヘキサンHexane:Acetone=30:1~2:1)にて精製すれば、[(4-メトキシ-2-メチル-フェニルカルバモイル)メチル]カルバミン酸tert-ブチルエステル(290mg)を無色油状物質として得る。
13C-NMR (100 MHz, CDCl3): δ 17.85, 28.21, 45.09, 55.23, 80.32, 111.34, 115.82, 125.26, 128.09, 132.42, 156.44, 157.17, 168.34
IR (neat): 1680, 3290 cm-1
MS (EI): m/z 294 (M+)
収率:99%
同様の反応により以下の化合物を得た。
溶媒を留去し、得られた残渣をシリカゲルカラムクロマトグラフィー(15g,ヘキサン:アセトン=6:~3 :1)で精製すれば、[(2,6-ジフルオロフェニルカルバモイル)メチル]カルバミン酸tert-ブチルエステル(1.73g)を無色結晶物質として得る。
1H-NMR (400 MHz, CDCl3): δ 1.47 (9H, s), 4.00 (2H, d, J = 4.6 Hz), 5.22 (1H, br), 6.96, (2H, t, J = 8.1 Hz), 7.18-7.27 (1H, m), 7.74 (1H, br)
IR (KBr): 1684, 3281 cm-1
MS (EI): m/z 286 (M+)
融点:119-120℃
1H-NMR (400 MHz, CDCl3): δ 1.43 (9H, s), 2.31 (3H, s), 3.82 (2H, d, J = 6.1 Hz), 4.46 (2H, d, J = 5.6 Hz), 5.10 (1H, br), 6.22 (1H, br), 7.18-7.20 (4H, m)
1H-NMR (400 MHz, CDCl3): δ 1.43 (9H, s), 3.82 (2H, d, J = 6.1 Hz), 4.41 (2H, d, J = 5.9 Hz), 5.12 (1H, br), 6.50 (1H, br), 7.15 (2H, d, J = 8.4 Hz), 7.45 (2H, d, J = 8.4 Hz)
1H-NMR (400 MHz, CDCl3): δ 1.44 (9H, s), 3.80 (2H, d, J = 6.1 Hz), 4.45 (2H, d, J = 6.1 Hz), 5.07 (1H, br), 6.51 (1H, br), 7.20-7.29 (3H, m)
1H-NMR (400 MHz, CDCl3): δ 1.47 (9H, s), 3.90 (2H, d, J = 6.1 Hz), 5.20 (1H, br), 7.16 (1H, t, J = 8.1 Hz), 7.22-7.25 (1H, m), 7.39 (1H, d, J = 8.1 Hz), 7.75 (1H, s), 8.25 (1H, br)
1H-NMR (400 MHz, CDCl3): δ 1.48 (9H, s), 3.94 (2H, d, J = 5.9 Hz), 5.25 (1H, br), 7.47 (1H, t, J = 7.9 Hz), 7.88 (1H, d, J = 7.9 Hz), 7.94 (1H, d, J = 7.9 Hz), 8.37 (1H, s), 8.67 (1H, br)
1H-NMR (400 MHz, CDCl3): δ 1.55 (9H, s), 4.34 (2H, d, J = 6.1 Hz), 5.40 (1H, br), 6.98 (2H, t, J = 8.2 Hz), 7.30 (1H, t, J = 8.2 Hz), 9.59 (1H, br)
溶媒を留去した残渣をシリカゲルカラムクロマトグラフィー(15g,ヘキサン:アセトン=6:1~3:1)にて精製すれば、[(2,6-ジフルオロ-フェニルカルバモイル)-メチル]-カルバミン酸tert-ブチルエステル(1.73g) を無色結晶物質として得る。
融点:119-120℃
1H-NMR (400 MHz, CDCl3): δ 1.47 (9H, s), 4.00 (2H, d, J = 4.6 Hz), 5.22 (1H, br), 6.96, (2H, t, J = 8.1 Hz), 7.18-7.27 (1H, m), 7.74 (1H, br)
同様の反応により以下の化合物を得る。
融点:118-119℃
1H-NMR (400 MHz, CDCl3): δ 1.49 (9H, s), 3.98 (2H, d, J = 5.6 Hz), 5.18 (1H, br), 6.99 (1H, td, J = 8.1, 1.3 Hz), 7.32 (1H, td, J = 8.1, 1.3 Hz), 7.54 (1H, dd, J = 8.1, 1.3 Hz), 8.37 (1H, dd, J = 8.1, 1.3 Hz), 8.47 (1H, br)
13C-NMR (100 MHz, CDCl3): δ 28.26, 45.49, 80.67, 113.38, 121.62, 125.33, 128.31, 132.23, 135.16, 156.04, 167.92
溶媒を留去した残渣をシリカゲルカラムクロマトグラフィー(20g,ヘキサン:アセトン=10:1)にて精製すれば、tert-ブトキシカルボニルアミノ酢酸ベンジルエステルの無色油状物質(360mg,68%)を得る。
その後反応液に0℃にて飽和重曹水を水槽が中性を示すまで加える。
エタノールを留去後、塩化メチレンで抽出した有機層を硫酸ナトリウムで乾燥し、ろ過した後溶媒を留去すれば、エチルエステル体の無色結晶物(910mg,100%)を得る。
エチルエステル体(500mg,2.74mmol)のエタノール(2.0mL)溶液にヒドラジン・一水和物(0.13mL,2.74mmol)を加え、終夜加熱還流する。
溶媒を留去すれば、ヒドラジド体の無色結晶物を得る。
次に、アルゴン雰囲気下、N-カルボベンゾキシグリシン(573mg,2.74mmol)の塩化メチレン(7mL)溶液に1,1-カルボジイミダゾール(488mg,3.01mmol)を加え、室温で1時間撹拌後、得られたヒドラジド体の塩化メチレン(3mL)溶液をカニューレを用いて加え、室温で終夜撹拌する。
溶媒を留去した残渣をシリカゲルカラムクロマトグラフィー(20g,塩化メチレン:メタノール=80:1~30:1)にて精製すれば[N’-[2-(4-フルオロフェニル)アセチル]ヒドラジノカルバモイルメチル]カルバミン酸ブチルエステルの無色結晶物(840mg)を得る。
融点:185-186℃
1H-NMR (400 MHz, CDCl3): δ 3.45 (2H, s), 3.65 (2H, d, J = 5.9 Hz), 5.01 (2H, s), 7.12 (2H, t, J = 8.7 Hz), 7.31 (2H, dd, J = 8.7, 5.7 Hz), 7.33-7.34 (5H, m), 7.51 (1H, br), 9.92 (1H, br), 10.08 (1H, br)
次に、4-メチルスチレン(1.31mL,10.0mmol)を加え、90℃にて4時間撹拌した。
室温に戻した後、氷水(25mL)を加えた。
その後反応液を吸引ろ過し、水で洗浄し、2-p-トリルエタンスルホニルクロライド(2-p-Tolyl-ethanesulfonyl chloride;1.134g,52%)を得た。
アルゴン雰囲気下、4-ヒドロキシベンズアルデヒド(500mg,4.09mmol)のアセトン(5mL)溶液にヨウ化メチル(0.76mL,12.27mmol),炭酸カリウム(2.26g,16.36mmol)を順次加え、終夜加熱還流する。
その後反応液を塩化メチレン(10mL)で希釈し、セライトろ過し、溶媒を留去する。
残渣をシリカゲルカラムクロマトグラフィー(20g,ヘキサン:アセトン=50:1~30:1)にて精製すれば、4-メトキシベンズアルデヒド(439 mg,収率:79%)を得る。
参考文献:Tetrahedron, 2011, 67, 8120-8130.
同様の反応により以下の化合物を得る
収率:84%
参考文献:Bioorg. Med. Chem., 2004, 13, 433-441.
アルゴン雰囲気下、1,3,5,-トリクロロベンゼン(724mg,4.00mmol)のテトラヒドロフラン(10mL)溶液に、-78℃にてn-ブチルリチウム(2.45mL,4.00mmol)を加え、45分間撹拌する。
次いで、-78℃にてジメチルホルムアミド(0.31mL,4.00mmol)を加え、45分間撹拌する。
-20℃まで昇温した後、飽和塩化アンモニウム水溶液(5mL)を加え、5分間撹拌する。
その後、酢酸エチルで抽出した有機層を硫酸ナトリウムで乾燥し、ろ過後溶媒を留去する。
残渣をシリカゲルカラムクロマトグラフィー(15g,ヘキサン:アセトン=50:1~40:1)にて精製すれば、無色結晶の2,4,6-トリクロロベンズアルデヒド体 (633 mg,76%)を得る。
参考文献:Synthesis, 2008, 279-285.
アルゴン雰囲気下、4-クロロベンズアルデヒド(141mg,1.00mmol)のトルエン(5mL)溶液にマロン酸(156mg,1.50mmol), ピリジン(0.12mL,1.54mmol),アニリン(0.01mL,0.12mmol)を順次加え、終夜加熱還流する。
10%塩酸水溶液を水層が酸性を示すまで加え、酢酸エチルで抽出した有機層を硫酸ナトリウムで乾燥し、ろ過後溶媒を留去する。
残渣をシリカゲルカラムクロマトグラフィー(20g,塩化メチレン:メタノール=100:1~40:1)にて精製すれば、無色結晶の3-(4-クロロフェニル)アクリル酸(162mg,89%) を得る。
参考文献:J. Org. Chem., 2008, 73, 5766-5775.
同様にして以下の化合物を得た。
収率:100%
参考文献:Org. Biomol. Chem., 2009, 7, 4062-4066.
・3-(4-フルオロフェニル)アクリル酸
収率:86%
参考文献:Chem. Eur. J.,2000, 6, 3386-3390.
・3-(2,4-ジメトキシフェニル)アクリル酸
収率:95%
参考文献:Synth. Commun., 1980, 10, 37-42.
・3-(4-イソプロピルフェニル)アクリル酸
収率:90%
参考文献:Synth. Commun., 2002,32, 195-201.
・3-(ビフェニル-4-イル)アクリル酸
収率:60%
参考文献:J. Med. Chem., 1993, 36, 2381-2389.
・3-(2,6-ジメトキシフェニル)アクリル酸
収率:100%
参考文献:J. Org. Chem., 1995, 60,1981-1984.
・3-(4-トリフルオロメチルフェニル)アクリル酸
収率:100%
参考文献:J. Org. Chem., 1999, 64, 3975-3978.
(1)アルゴン雰囲気下、水素化ナトリウム(133mg, 3.32mmol)のテトラヒドロフラン(5mL)溶液に、0℃にてトリエチルホスホンアセテ-ト(0.66mL,3.32mmol)を加え、30分間撹拌後、2,4,6-トリクロロベンズアルデヒド(580mg,2.77mmol)のテトラヒドロフラン(5mL)の溶液をカニューレを用いて加え、室温で終夜撹拌する。
溶媒を留去後、水(10mL)を加え、塩化メチレンで抽出した有機層を硫酸ナトリウムで乾燥し、ろ過後溶媒を留去する。
残渣をシリカゲルカラムクロマトグラフィー(15g,ヘキサン:アセトン=90:1~80:1)にて精製すれば、無色油状の3-(2,4,6-トリクロロフェニル)アクリル酸エチルエステル(751mg,97%)を得る。
溶媒を留去後、10%塩酸水溶液を水層が酸性を示すまで加え、酢酸エチルで抽出した有機層を硫酸ナトリウムで乾燥し、ろ過後溶媒を留去すれば、無色結晶の3-(2,4,6-トリクロロフェニル)アクリル酸(654mg,97%)を得る。
1H-NMR (400 MHz, CDCl3): δ 6.64 (1H, d, J = 16.2 Hz), 7.41 (2H, s), 7.82 (1H, d, J = 16.2 Hz)
・3-(3,5-ジブロモフェニル)アクリル酸
収率:100%
参考文献:WO2004/046122
・3-(2,4,6-トリフルオロフェニル)アクリル酸
収率:99%
参考文献:WO2001/092239
溶媒を留去した後、新たに塩化メチレン(3mL)を加え、次にチオシアン酸アンモニウム(63mg,0.82mmol)、PEG-400(1滴)を順次加え、室温で2時間撹拌する。
溶媒を留去し、残渣をシリカゲルカラムクロマトグラフィー(15g,ヘキサン:アセトン=50:1~40:1)にて精製すれば、無色結晶の3-(4-クロロフェニル)アクロイル イソチオシアネート(105mg,85%)を得る。
1H-NMR (400 MHz, CDCl3) δ: 6.48 (1H, d, J = 16.1 Hz), 7.41 (2H, d, J = 8.7 Hz), 7.50 (2H, d, J = 8.7 Hz), 7.72 (1H, d, J = 15.6 Hz); Yield: 85 %.
同様にして以下の化合物を得た。
収率:80%
収率:88%
収率:73%
収率:63%
収率:79%
収率:83%
収率:27%
収率:67%
収率:85%
溶媒を留去し、残渣をシリカゲルカラムクロマトグラフィー(15g,ヘキサン:アセトン=50:1~40:1)にて精製すれば、無色結晶のフェニルアセチル イソチオシアネート(132mg,75 %) を得る。
同様にして以下の化合物を得た。
溶媒を留去した後、塩化メチレン(5mL)を加え、次にチオシアン酸アンモニウム(114mg,1.50mmol)、PEG-400(4滴)を順次加え、室温で終夜撹拌する。
溶媒を留去した残渣をシリカゲルカラムクロマトグラフィー(15g,ヘキサン:アセトン=50:1~40:1)にて精製すれば、無色結晶の(2,6-ジフルオロフェニル)アセチル イソチオシアネート(105mg,49%)を得る。
参考文献:WO2009/125597
溶媒を留去した後、塩化メチレン(5mL)を加え、次にチオシアン酸アンモニウム(114mg,1.50mmol),PEG-400(4滴)を順次加え、室温で2終夜撹拌する。
溶媒を留去した残渣をシリカゲルカラムクロマトグラフィー(15g,ヘキサン:アセトン=80:1~70:1)にて精製すれば、無色結晶の(シクロヘキシル)アセチル イソチオシアネート(120mg,66%)を得る。
参考文献:WO2007/054831
溶媒を留去した後、新たに塩化メチレン(5mL)を加え、次にシアン化チオアンモニウム(228mg,3.00mmol),ポリエチレングリコール(PEG-400;6drops)を順次加え、室温で終夜撹拌した。
溶媒を留去した残渣をシリカゲルカラムクロマトグラフィー(15g,Hexane:Acetone=100:1)にて精製し、無色結晶のチオフェン-2-イル-アセチルクロライドを133mg(36%)を得た。
その後、水10mLを加える。
塩化メチレンで抽出した有機層を硫酸ナトリウムで乾燥しろ過する。
溶媒を留去すればアミン化合物2aを得を得る。
同様の反応により以下の化合物を得る
その後、水5mLを加える。
塩化メチレンで抽出した有機層を飽和食塩水5mLで洗浄し、硫酸ナトリウムで乾燥し、ろ過する。
溶媒を留去した残渣をシリカゲルカラムクロマトグラフィー(15g,ヘキサン:アセトン=10:1)にて精製すれば、N-(2-アミノフェニル)-4-メチルベンゼンスルホアミドの無色結晶218mg(収率:54%)を得た。
参考文献:Angew. Chem. Int. Ed., 2007, 46, 7247-7250.
溶媒を留去した残渣に水(5mL)を加え、塩化メチレンで抽出した有機層を飽和食塩水(5mL)で洗浄し、硫酸ナトリウムで乾燥し、ろ過後溶媒を留去した。
得られた残渣をエタノール-水で再結晶し、
2-p-トリル-エタンスルフォニル酸(2-アミノ-フェニル)-アミド(384mg, 91%)を無色結晶物質として得た。
溶媒を留去後、10 %塩酸水溶液を水層が酸性を示すまで加え、酢酸エチルで抽出する。
有機層を硫酸ナトリウムで乾燥し、ろ過後、溶媒を留去するれば、フェノキシ酢酸(92mg)を無色結晶物質として得る。
その後反応液に0℃にて飽和重曹水を水層が塩基性を示すまで加え、塩化メチレンで抽出する。
有機層を炭酸カリウムで乾燥し、ろ過後、溶媒を留去すれば、2-アミノ-N-(4-メトキシ-2-メチルフェニル)アセトアミド(146mg)を無色結晶物質として得る。
溶媒を留去し、得られた残渣をシリカゲルカラムクロマトグラフィー(15g,ヘキサン:アセトン=5:1~3:1)にて精製すれば、N-[(4-メトキシ-2-メチルフェニルカルバモイル)メチル]-2-フェノキシアセトアミド(113mg)を無色結晶物質として得る。
<MM-1>
融点:165-166℃(再結晶溶媒:アセトン)
1H-NMR (400 MHz, CDCl3): δ 2.19 (3H, s), 3.76 (3H, s), 4.16 (2H, d, J = 5.9 Hz), 4.57 (2H, s), 6.72 (2H, m), 6.92 (2H, d, J = 7.6 Hz), 7.01 (1H, t, J = 7.6 Hz), 7.30 (2H, t, J = 7.6 Hz), 7.38 (1H, br), 7.52 (1H, d, J = 9.5 Hz), 7.62 (1H, br)
13C-NMR (100 MHz, DMSO-d6): δ 17.95, 42.06, 55.09, 66.86, 111.15, 114.74, 115.32, 121.20, 126.67, 128.81, 129.50, 134.03, 156.83, 157.68, 167.49, 168.21
IR (KBr): 1668, 3258 cm-1
MS (EI): m/z 328 (M+)
融点:170-171℃(再結晶溶媒:アセトン)
1H-NMR (400 MHz, CDCl3): δ 2.20 (3H, s), 3.76 (3H, s), 4.16 (2H, d, J = 5.6 Hz), 4.53 (2H, s), 6.71-6.73 (2H, m), 6.85 (2H, d, J = 9.0 Hz), 7.24-7.27 (2H, m), 7.35 (1H, br), 7.50 (1H, d, J = 9.5 Hz), 7.56 (1H, br)
13C-NMR (100 MHz, DMSO-d6): δ 17.95, 42.03, 55.09, 67.10, 111.15, 115.32, 116.55, 124.91, 126.68, 128.80, 129.23, 134.05, 156.57, 156.83, 167.45, 167.91
IR (KBr): 1666, 3267 cm-1
MS (EI): m/z 362 (M+)
融点:159-160℃(再結晶溶媒:アセトン)
1H-NMR (400 MHz, CDCl3): 2.19 (3H, s), 3.76 (3H, s), 4.16 (2H, d, J = 5.6 Hz), 4.52 (2H, s), 6.71-6.73 (2H, m), 6.81 (2H, d, J = 8.8 Hz), 7.36 (1H, br), 7.40 (2H, d, J = 8.8 Hz), 7.50 (1H, d, J = 9.5 Hz), 7.59 (1H, br)
13C-NMR (100 MHz, DMSO-d6): δ 17.95, 55.10, 67.03, 100.08, 111.16, 112.63, 115.32, 117.07, 126.69, 128.79, 132.12, 134.05, 156.83, 157.02, 167.44, 167.88
IR (KBr): 1663, 3273 cm-1
MS (EI): m/z 406 (M+)
融点:205-206℃(再結晶溶媒:アセトン)
1H-NMR (400 MHz, CDCl3): δ 4.13 (2H, d, J = 5.6 Hz), 4.54 (2H, s), 6.86 (2H, d, J = 9.0 Hz), 7.24-7.28 (3H, m), 7.27 (2H, d, J = 9.0 Hz), 7.61 (2H, d, J = 8.8 Hz), 7.98 (1H, br)
13C-NMR (100 MHz, DMSO-d6): δ 42.42, 67.05, 86.74, 116.56, 121.33, 124.95, 129.23, 137.39, 138.62, 156.52, 167.52, 167.94
IR (KBr): 1663, 3294 cm-1
MS (EI): m/z 444 (M+)
融点:211-212℃(再結晶溶媒:アセトン)
1H-NMR (400 MHz, CDCl3): δ 4.13 (2H, d, J = 5.6 Hz), 4.53 (2H, s), 6.81 (2H, d, J = 8.8 Hz), 7.24-7.30 (3H, m), 7.41 (2H, d, J = 8.8 Hz), 7.61 (2H, d, J = 8.8 Hz), 7.98 (1H, br)
13C-NMR (100 MHz, DMSO-d6): δ 42.43, 66.99, 86.75, 112.69, 117.08, 121.34, 132.14, 137.40, 138.63, 156.98, 167.53, 167.93
IR (KBr): 1661, 3290 cm-1
MS (EI): m/z 488 (M+)
融点:169-170℃(再結晶溶媒:アセトン)
1H-NMR (400 MHz, CDCl3): δ 2.22 (3H, s), 3.78 (3H, s), 4.18 (2H, d, J = 5.6 Hz), 4.54 (2H, s), 6.74-6.75 (2H, m), 6.89 (2H, dd, J = 8.9, 4.1 Hz), 7.01 (2H, t, J = 8.9 Hz), 7.38 (1H, br), 7.54 (1H, d, J = 9.8 Hz), 7.59 (1H, br)
13C-NMR (100 MHz, DMSO-d6): δ 17.93, 42.03, 55.08, 67.48, 111.14, 115.31, 115.82 (d, J = 22.3 Hz), 116.12 (d, J = 8.3 Hz), 126.67, 128.81, 134.03, 154.05 (d, J = 2.5 Hz), 156.82, 156.84 (d, J = 236.5 Hz), 167.47, 168.09
IR (KBr): 3260, 1666 cm-1
MS (EI): m/z 346 (M+)
融点:190-191℃(再結晶溶媒:アセトン)
1H-NMR (400 MHz, CDCl3): δ 4.17 (2H, d, J = 4.9 Hz), 4.55 (2H, s), 6.90 (2H, dd, J = 8.8, 4.0 Hz), 7.02 (2H, t, J = 8.8 Hz), 7.12 (1H, br), 7.29 (2H, d, J = 8.5 Hz), 7.38 (1H, br), 7.63 (2H, d, J = 8.5 Hz)
13C-NMR (100 MHz, DMSO-d6): δ 42.41, 67.44, 86.73, 115.85 (d, J = 23.2 Hz), 116.14 (d, J = 8.3 Hz), 121.34, 137.39, 138.64, 154.02 (d, J = 2.5 Hz), 156.87 (d, J = 236.6 Hz), 167.55, 168.13
IR (KBr): 3312, 1672 cm-1
MS (EI): m/z 428 (M+)
融点:213-214℃(再結晶溶媒:アセトン)
1H-NMR (400 MHz, CDCl3): δ 4.13 (2H, d, J = 5.9 Hz), 4.53 (2H, s), 6.82 (2H, d, J = 8.9 Hz), 7.00 (2H, d, J = 8.5 Hz), 7.31 (1H, br), 7.40-7.44 (2H, m), 7.41 (2H, d, J = 8.9 Hz), 7.95 (1H, br)
13C-NMR (100 MHz, DMSO-d6): δ 42.28, 66.98, 112.65, 115.28 (d, J = 22.3 Hz), 117.07, 120.90 (d, J = 7.4 Hz), 132.11, 135.18 (d, J = 2.5 Hz), 156.99, 157.96 (d, J = 239.8 Hz), 167.24, 167.88
IR (KBr): 3389, 1657 cm-1
MS (EI): m/z 380 (M+)
融点:202-203℃(再結晶溶媒:アセトン)
1H-NMR (400 MHz, CDCl3): δ 4.14 (2H, d, J = 5.9 Hz), 4.53 (2H, s), 6.88 (2H, dd, J = 9.3, 4.1 Hz), 6.98-7.02 (4H, m), 7.34 (1H, br), 7.43 (2H, dd, J = 9.0, 4.6 Hz), 7.99 (1H, br)
13C-NMR (100 MHz, DMSO-d6): δ 42.30, 67.44, 115.33 (d, J = 22.3 Hz), 115.87 (d, J = 23.2 Hz), 116.14 (d, J = 8.3 Hz), 120.92 (d, J = 7.4 Hz), 135.22 (d, J = 1.7 Hz), 154.04 (d, J = 1.7 Hz), 156.88 (d, J = 236.5 Hz), 158.00 (d, J = 239.0 Hz), 167.32, 168.16
IR (KBr): 3296, 1672 cm-1
MS (EI): m/z 320 (M+)
融点:192-193℃(再結晶溶媒:アセトン)
1H-NMR (400 MHz, CDCl3): δ 4.15 (2H, d, J = 5.6 Hz), 4.53 (2H. s), 6.88 (2H, dd, J = 8.9, 4.3 Hz), 7.00 (2H, t, J = 8.9 Hz), 7.38 (2H, d, J = 9.1 Hz), 7.39 (1H, br), 7.42 (2H, d, J = 9.1 Hz), 8.22 (1H, br)
13C-NMR (100 MHz, DMSO-d6): δ 42.40, 67.40, 114.83, 115.85 (d, J = 23.2 Hz), 116.12 (d, J = 8.3 Hz), 121.05, 131.56, 138.20, 154.01 (d, J = 2.5 Hz), 156.85 (d, J = 236.6 Hz), 167.59, 168.16
IR (KBr): 1686, 3256 cm-1
MS (EI): m/z 380 (M+)
融点:190-191℃(再結晶溶媒:アセトン)
1H-NMR (400 MHz, CDCl3): δ 3.79 (3H, s), 4.15 (2H, d, J = 5.6 Hz), 4.55 (2H, s), 6.84 (2H, d, J = 9.0 Hz), 6.86 (2H, d, J = 8.9 Hz), 7.34 (1H, br), 7.38 (2H, d, J = 9.0 Hz), 7.43 (2H, d, J = 8.9 Hz), 7.78 (1H, br)
13C-NMR (100 MHz, DMSO-d6): δ 42.22, 55.12, 66.98, 112.66, 113.85, 117.07, 120.73, 131.91, 132.14, 155.21, 156.99, 166.80, 167.84
IR (KBr): 1655, 3261 cm-1
MS (EI): m/z 392 (M+)
融点:185-186℃(再結晶溶媒:アセトン)
1H-NMR (400 MHz, CDCl3): δ 3.80 (3H, s), 4.16 (2H, d, J = 5.6 Hz), 4.55 (2H, s), 6.86-6.92 (2H, m), 6.87 (2H, d, J = 8.9 Hz), 7.02 (2H, t, J = 8.5 Hz), 7.38 (1H, br), 7.39 (2H, d, J = 8.9 Hz), 7.80 (1H, br)
13C-NMR (100 MHz, DMSO-d6): δ 42.24, 55.14, 67.45, 113.87, 115.88 (d, J = 23.2 Hz), 116.15 (d, J = 7.4 Hz), 120.76, 131.96, 154.05 (d, J = 1.7 Hz), 155.24, 156.88 (d, J = 236.5 Hz) 166.86, 168.10
IR (KBr): 1659, 3279 cm-1
MS (EI): m/z 332 (M+)
融点:210-211℃(再結晶溶媒:アセトン)
1H-NMR (400 MHz, CDCl3): δ 1.12-1.19 (3H, m), 1.31-1.38 (3H, m), 1.53-1.61 (1H, m), 1.67-1.75 (2H, m), 1.88-1.93 (2H, m), 3.76 (1H, br), 3.96 (2H, d, J = 5.4 Hz), 4.51 (2H, s), 5.64 (1H, br), 6.83 (2H, d, J = 9.1 Hz), 7.42 (2H, d, J = 9.1 Hz)
13C-NMR (100 MHz, DMSO-d6): δ 24.53, 25.17, 32.37, 41.59, 47.53, 66.94, 112.63, 117.03, 132.14, 156.97, 167.19, 167.56
IR (KBr): 1653, 3290 cm-1
MS (EI): m/z 370 (M+)
融点:184-185℃(再結晶溶媒:アセトン)
1H-NMR (400 MHz, CDCl3): δ 1.12-1.18 (3H, m), 1.31-1.40 (3H, m), 1.53-1.64 (1H, m), 1.67-1.75 (2H, m), 1.85-1.95 (2H, m), 3.78 (1H, br), 3.96 (2H, d, J = 5.4 Hz), 4.50 (2H, s), 5.68 (1H, br), 6.89 (2H, dd, J = 8.8, 4.3 Hz), 7.01 (2H, t, J = 8.8 Hz)
13C-NMR (100 MHz, DMSO-d6): δ 24.56, 25.20, 32.40, 41.61, 47.59, 67.42, 115.88 (d, J = 23.2 Hz), 116.11 (d, J = 8.3 Hz), 154.03 (d, J = 1.7 Hz), 156.88 (d, J = 236.5 Hz), 167.27, 167.83
IR (KBr): 1653, 3292 cm-1
MS (EI): m/z 308 (M+)
融点:173-174℃
1H-NMR (400 MHz, CDCl3): δ 4.22 (2H, d, J = 1.5 Hz), 4.53 (2H, s), 6.81 (2H, d, J = 9.0 Hz), 6.95 (2H, t, J = 8.4 Hz), 7.04 (1H, br), 7.21-7.24 (1H, m), 7.40 (2H, d, J = 9.0 Hz), 7.50 (1H, br)
IR (KBr): 1661, 3261 cm-1
融点:195-196℃(再結晶溶媒:アセトン)
1H-NMR (400 MHz, CDCl3): δ 4.02 (2H, d, J = 5.4 Hz), 4.44 (2H, d, J = 5.9 Hz), 4.48 (2H, s), 6.12 (1H, br), 6.79 (2H, d, J = 9.1 Hz), 6.98 (1H, br), 7.24-7.35 (5H, m), 7.38 (2H, d, J = 9.1 Hz)
13C-NMR (100 MHz, DMSO-d6): δ 41.80, 41.99, 66.99, 112.61, 117.04, 126.73, 127.15, 128.21, 132.13, 139.30, 156.99, 167.80, 168.55
IR (KBr): 1653, 3277 cm-1
MS (EI): m/z 376 (M+)
融点:165-166℃(再結晶溶媒:アセトン)
1H-NMR (400 MHz, CDCl3): δ 4.03 (2H, d, J = 5.6 Hz), 4.45 (2H, d, J = 5.6 Hz), 4.48 (2H, s), 6.16 (1H, br), 6.85 (2H, dd, J = 8.9, 4.1 Hz), 6.97 (2H, t, J = 8.9 Hz), 7.09 (1H, br), 7.22-7.35 (5H, m)
IR (KBr): 1655, 3263 cm-1
融点:143-144℃(再結晶溶媒:アセトン)
1H-NMR (400 MHz, CDCl3): δ 2.21 (3H, s), 3.76 (3H, s), 3.78 (3H, s), 4.17 (2H, d, J = 6.1 Hz), 4.53 (2H, s), 6.73-6.75 (2H, m), 6.84 (2H, d, J = 9.5 Hz), 6.88 (2H, d, J = 9.5 Hz), 7.39 (1H, br), 7.53 (1H, d, J = 9.5 Hz), 7.64 (1H, br)
13C-NMR (100 MHz, DMSO-d6): δ 17.95, 42.01, 55.08, 55.33, 67.61, 111.14, 114.56, 115.31, 115.72, 126.66, 128.81, 134.02, 151.70, 153.82, 156.80, 167.49, 168.41
IR (KBr): 1660, 3273 cm-1
MS (EI): m/z 358 (M+)
融点:115-116℃
1H-NMR (400 MHz, CDCl3): δ 2.21 (3H, s), 3.78-3.81 (6H, m), 4.18 (2H, d, J = 5.9 Hz), 4.57 (2H, s), 6.51-6.53 (2H, m), 6.58 (1H, d, J = 7.8 Hz), 6.73-6.75 (2H, m), 7.21 (1H, t, J = 7.8 Hz), 7.38 (1H, br), 7.52 (1H, d, J = 9.5 Hz), 7.65 (1H, br)
IR (KBr): 1659, 3331 cm-1
融点:184-185℃
1H-NMR (400 MHz, CDCl3): δ 4.22 (2H, d, J = 1.0 Hz), 4.54 (2H, s), 6.86 (2H, d, J = 9.0 Hz), 6.96 (2H, t, J = 8.2 Hz), 7.22-7.26 (1H, m), 7.26 (2H, d, J = 9.0 Hz), 7.30 (1H, br), 7.50 (1H, br)
IR (KBr): 1663, 3261 cm-1
融点:164-165℃(再結晶溶媒:トルエン)
1H-NMR (400 MHz, CDCl3): 4.25 (2H, d, J = 3.2 Hz), 4.55 (2H, s), 6.89-7.01 (9H, m), 7.05 (1H, t, J = 7.4 Hz), 7.29 (2H, t, J = 7.4 Hz), 7.37 (1H, br), 7.60 (1H, br)
13C-NMR (100 MHz, DMSO-d6): δ 41.58, 67.36, 111.88 (dd, J = 17.8, 5.4 Hz), 114.19 (t, J = 16.5 Hz), 116.14, 117.47, 120.58, 122.73, 128.06 (t, J = 10.3 Hz), 129.92, 150.06, 154.04, 157.73 (dd, J = 248.1, 5.8 Hz), 157.82, 167.91, 168.26
R (KBr): 1665, 3273 cm-1
融点:161-162℃(再結晶溶媒:トルエン)
1H-NMR (400 MHz, CDCl3): δ 2.33 (3H, s), 4.25 (2H, s), 4.57 (2H, s), 6.74 (1H, d, J = 8.3 Hz), 6.77 (1H, s), 6.83 (1H, d, J = 8.3 Hz), 6.97 (2H, t, J = 7.9 Hz), 7.19 (1H, t, J = 7.9 Hz), 7.20-7.27 (1H, m), 7.38 (1H, br), 7.61 (1H, br)
13C-NMR (100 MHz, DMSO-d6): δ 21.09, 41.56, 66.80, 111.87 (dd, J = 19.0, 5.8 Hz), 114.19 (t, J = 16.5 Hz), 115.44, 121.97, 128.04 (t, J = 9.9 Hz), 128.21, 129.25, 139.03, 157.69, 157.73 (dd, J = 248.1, 5.8 Hz), 167.88, 168.30
IR (KBr): 1680, 3258 cm-1
融点:164-165℃(再結晶溶媒:トルエン)
1H-NMR (400 MHz, CDCl3): δ 3.74 (3H, s), 4.23 (2H, s), 4.52 (2H, s), 6.82 (2H, d, J = 9.1 Hz), 6.86 (2H, d, J = 9.1 Hz), 6.95 (2H, t, J = 8.1 Hz), 7.24-7.25 (1H, m), 7.36 (1H, br), 7.61 (1H, br)
13C-NMR (100 MHz, DMSO-d6): δ 41.54, 55.35, 67.60, 111.88 (dd, J = 17.8, 5.4 Hz), 114.19 (t, J = 17.0 Hz), 114.59, 115.75, 128.04 (t, J = 12.0 Hz), 151.73, 153.85, 157.72 (dd, J = 249.4, 6.2 Hz), 167.90, 168.46
IR (KBr): 1666, 3271 cm-1
融点:194-195℃(再結晶溶媒:トルエン)
1H-NMR (400 MHz, CDCl3): δ 4.27 (2H, s), 4.54 (2H, s), 6.89 (2H, dd, J = 9.1, 4.3 Hz), 6.95-7.03 (4H, m), 7.22-7.26 (1H, m), 7.39 (1H, br), 7.67 (1H, br)
IR (KBr): 1663, 3261 cm-1
融点:174-175℃(再結晶溶媒:トルエン)
1H-NMR (400 MHz, CDCl3): δ 4.57 (2H, s), 4.59 (2H. s), 6.84 (2H, d, J = 9.0 Hz), 7.00 (2H, t, J = 7.7 Hz), 7.33 (1H, t, J = 7.7 Hz), 7.43 (2H, d, J = 9.0 Hz), 7.62 (1H, br), 9.46 (1H, br)
13C-NMR (100 MHz, DMSO-d6): δ 48.89, 67.03, 112.11 (dd, J = 18.2, 4.1 Hz), 112.63, 116.18 (t, J = 16.5 Hz), 117.09, 129.74 (t, J = 9.5 Hz), 132.12, 156.99, 157.49 (dd, J = 250.6, 5.8 Hz), 167.99, 203.40
IR (KBr): 1670, 3020, 3207 cm-1
融点:160-161℃(再結晶溶媒:トルエン)
1H-NMR (400 MHz, CDCl3): δ 3.74 (3H, s), 4.54 (2H, s), 4.57 (2H, d, J = 6.1 Hz), 6.83 (2H, d, J = 9.5 Hz), 6.87 (2H, d, J = 9.5Hz), 6.98 (2H, t, J = 8.1 Hz), 7.31 (1H, t, J = 8.1 Hz), 7.57 (1H, br), 9.45 (1H, br)
13C-NMR (100 MHz, DMSO-d6): δ 48.90, 55.35, 67.64, 112.13 (dd, J = 18.6, 4.5 Hz), 114.58, 115.75, 116.21 (t, J = 16.5 Hz), 129.75 (t, J = 9.9 Hz), 151.71, 153.83, 157.52 (dd, J = 249.8, 5.0 Hz), 168.53, 203.48
IR (KBr): 1670, 3007, 3182 cm-1
融点:174-175℃(再結晶溶媒:トルエン)
1H-NMR (400 MHz, CDCl3): δ 2.30 (3H, s), 4.01 (2H, d, J = 5.4 Hz), 4.44 (2H, d, J = 5.6 Hz), 4.46 (2H, s), 6.06 (1H, br), 6.79 (2H, d, J = 9.1 Hz), 7.14-7.24 (5H, m), 7.38 (2H, d, J = 9.1 Hz)
IR (KBr): 1649, 3275 cm-1
融点:208-209℃(再結晶溶媒:アセトン)
1H-NMR (400 MHz, CDCl3): δ 4.04 (2H, d, J = 5.4 Hz), 4.41 (2H, d, J = 6.1 Hz), 4.50 (2H, s), 6.26 (1H, br), 6.81 (2H, d, J = 9.0 Hz), 7.14 (2H, d, J = 8.5 Hz), 7.20-7.35 (1H, m), 7.41 (2H, d, J = 9.0 Hz), 7.46 (2H, d, J = 8.5 Hz)
IR (KBr): 1655, 3271 cm-1
融点:179-180℃(再結晶溶媒:トルエン)
1H-NMR (400 MHz, CDCl3): δ 4.02 (2H, d, J = 5.6 Hz), 4.45 (2H, d, J = 5.9 Hz), 4.50 (2H, s), 6.30 (1H, br), 6.81 (2H, d, J = 9.0 Hz), 7.19-7.26 (3H, m), 7.41 (2H, d, J = 9.0 Hz), 7.79 (1H, br)
13C-NMR (100 MHz, DMSO-d6): δ 35.60, 41.79, 66.96, 112.64, 117.02, 118.38 (d, J = 24.8 Hz), 120.07 (d, J = 9.1 Hz), 125.62 (d, J = 14.9 Hz), 127.37 (d, J = 3.3 Hz), 131.04 (d, J = 5.0 Hz), 132.12, 156.96, 159.81 (d, J = 249.8 Hz), 167.89, 168.86
IR (KBr): 1661, 3279 cm-1
融点:227-228℃
1H-NMR (400 MHz, CDCl3): δ 4.13 (2H, d, J = 5.9 Hz), 4.53 (2H, s), 6.81 (2H, d, J = 9.1 Hz), 7.16 (1H, t, J = 8.1 Hz), 7.22-7.35 (2H, m), 7.37 (1H, d, J = 8.1 Hz), 7.41 (2H, d, J = 9.1 Hz), 7.74 (1H, s), 8.18 (1H, br)
13C-NMR (100 MHz, DMSO-d6): δ 42.45, 66.97, 112.71, 117.08, 117.90, 121.48, 121.57, 125.93, 130.80, 132.15, 140.37, 156.98, 167.77, 168.00
IR (KBr): 1661, 3281 cm-1
融点:174-175℃
1H-NMR (400 MHz, CDCl3): δ 3.75 (3H, s), 4.16 (2H, d, J = 5.6 Hz), 4.53 (2H, s), 6.83 (2H, d, J = 9.3 Hz), 6.87 (2H, d, J = 9.3 Hz), 7.16 (1H, t, J = 7.8 Hz), 7.22-7.24 (1H, m), 7.39 (1H, d, J = 7.8 Hz), 7.40 (1H, br), 7.74 (1H, s), 8.33 (1H, br)
13C-NMR (100 MHz, DMSO-d6): δ 42.43, 55.36, 67.59, 114.60, 115.77, 117.90, 121.48, 121.57, 125.92, 130.81, 140.41, 151.70, 153.87, 167.83, 168.53
IR (KBr): 1663, 3312 cm-1
融点:205-206℃(再結晶溶媒:トルエン)
1H-NMR (400 MHz, CDCl3): δ 4.14 (2H, d, J = 5.9 Hz), 4.54 (2H, s), 6.82 (2H, d, J = 9.0 Hz), 7.09 (1H, d, J = 8.3 Hz), 7.21-7.28 (2H, m), 7.30 (1H, d, J = 8.3 Hz), 7.41 (2H, d, J = 9.0 Hz), 7.61 (1H, s), 8.10 (1H, br)
13C-NMR (100 MHz, DMSO-d6): δ 42.42, 66.95, 112.70, 117.07, 117.49, 118.60, 123.01, 130.47, 132.14, 133.08, 140.23, 156.97, 167.77, 167.99
IR (KBr): 1661, 3281 cm-1
融点:197-198℃
1H-NMR (400 MHz, CDCl3): δ 4.22 (2H, d, J = 5.9 Hz), 4.58 (2H, s), 6.84 (2H, d, J = 8.7 Hz), 7.41 (1H, br), 7.42 (2H, d, J = 8.7 Hz), 7.48 (1H, t, J = 8.5 Hz), 7.90 (1H, d, J = 8.5 Hz), 7.96 (1H, d, J = 8.5 Hz), 8.39 (1H, s), 8.76 (1H, br)
13C-NMR (100 MHz, DMSO-d6): δ 42.51, 66.95, 112.69, 113.22, 117.06, 117.81, 125.08, 130.20, 132.13, 139.91, 147.92, 156.96, 168.07, 168.21
IR (KBr): 1676, 3265 cm-1
融点:145-146℃
1H-NMR (400 MHz, CDCl3): δ 4.26 (2H, s), 4.53 (2H, s), 5.00 (2H, s), 6.87 (2H, d, J = 9.1 Hz), 6.92 (2H, d, J = 9.1 Hz), 6.96 (2H, t, J = 8.1 Hz), 7.30-7.42 (7H, m), 7.66 (1H, br)
IR (KBr): 1663, 3260 cm-1
融点:192-193℃(再結晶溶媒:トルエン)
1H-NMR (400 MHz, CDCl3): δ 2.34 (3H, s), 4.16 (2H, d, J = 5.9 Hz), 4.57 (2H, s), 6.74 (1H, d, J = 7.7 Hz), 6.77 (1H, s), 6.86 (1H, d, J = 7.7 Hz), 7.20 (1H, t, J = 7.7 Hz), 7.26-7.28 (2H, m), 7.37 (1H, br), 7.62 (2H, J = 8.8 Hz), 8.21 (1H, br)
13C-NMR (100 MHz, DMSO-d6): δ 21.10, 42.42, 66.75, 86.75, 111.73, 115.40, 121.30, 121.98, 129.23, 137.40, 138.65, 139.02, 157.64, 167.59, 168.31
IR (KBr): 1663, 3277 cm-1
融点:169-170℃
1H-NMR (400 MHz, CDCl3): δ 2.33 (3H, s), 4.16 (2H, d, J = 5.6 Hz), 4.57 (2H, s), 5.05 (2H, s), 6.74 (1H, d, J = 7.8 Hz), 6.77 (1H, s), 6.85 (1H, d, J = 7.8 Hz), 6.93 (2H, d, J = 9.0 Hz), 7.20 (1H, t, J = 7.8 Hz), 7.32-7.43 (8H, m), 7.91 (1H, br)
IR (KBr): 1663, 3329 cm-1
反応液をセライトろ過後溶媒を留去すれば、N-[(2,6-ジフルオロフェニルカルバモイル)メチル]-2-(4-ヒドロキシフェノキシ)-アセトアミド(72mg)を無色結晶物質として得る。
<MM-35>
融点:197-198℃
1H-NMR (400 MHz, CDCl3): δ 3.98 (2H, s), 4.41 (2H, s), 6.67 (2H, d, J = 8.8 Hz), 6.81 (2H, d, J = 8.8 Hz), 7.14 (2H, t, J = 7.6 Hz), 7.32 (1H, t, J = 7.6 Hz), 8.35 (1H, br), 9.72 (1H, br)
IR (KBr): 1680, 3261 cm-1
反応液をセライトろ過後溶媒を留去すれば、N-[(4-ヒドロキシフェニルカルバモイル)メチル]-2-m-トリルオキシ-アセトアミド(154mg)を無色結晶物質として得る。
<MM37>
融点:186-187℃
1H-NMR (400 MHz, DMSO-d6): δ 2.27 (3H, s), 3.90 (2H, d, J = 5.4 Hz), 4.51 (2H, s), 6.68 (2H, d, J = 8.4 Hz), 6.77-6.82 (3H, m), 7.17 (1H, t, J = 7.7 Hz), 7.33 (2H, d, J = 8.4 Hz), 8.30 (1H, br), 9.20 (1H, br), 9.71 (1H, m)
13C-NMR (100 MHz, DMSO-d6): δ 21.13, 42.26, 66.82, 111.78, 115.15, 115.45, 121.04, 122.02, 129.29, 130.43, 139.09, 153.52, 157.72, 166.69, 168.27
IR (KBr): 1663, 3339 cm-1
その後反応液に0℃にて飽和重曹水を水層が塩基性を示すまで加える。
水層に塩化メチレンを加え、抽出した有機層を炭酸カリウムで乾燥し、ろ過する。
溶媒を留去すれば、無色結晶の2-アミノ-N-(2,6-ジフルオロフェニル)アセトアミド(122mg, 収率:49%)を得る。
溶媒を留去した残渣をシリカゲルカラムクロマトグラフィー(15g,ヘキサン:アセトン=4:1~3:1)にて精製すれば、無色結晶のN-(2,6-ジフルオロフェニル)-2-フェニルメタンスルフォニルアミノ-アセタミド(113mg,DR-1)
融点:141-142℃(再結晶溶媒:トルエン)
1H-NMR (400 MHz, CDCl3): δ 3.77 (2H, s), 4.35 (2H, s), 5.00 (1H, br), 6.94 (2H, t, J = 8.2 Hz), 7.19-7.24 (1H, m), 7.37-7.43 (6H, m)
融点:129-130℃(再結晶溶媒:トルエン)
1H-NMR (400 MHz, CDCl3): δ 2.42 (3H, s), 3.79 (2H, s), 5.36 (1H, br), 6.93 (2H, t, J = 8.2 Hz), 7.17-7.24 (1H, m), 7.32 (2H, d, J = 8.2 Hz), 7.72 (1H, br), 7.76 (2H, d, J =8.2 Hz)
融点:147-148℃(再結晶溶媒:トルエン)
1H-NMR (400 MHz, CDCl3): δ 1.46 (3H, d, J = 7.1 Hz), 3.52 (2H, s), 4.27 (2H, s), 4.90 (1H, br), 5.06 (1H, quint, J = 7.1 Hz), 6.27 (1H, br), 7.24-7.35 (10H, m)
1H-NMR (400 MHz, CDCl3): δ 1.42 (3H, d, J = 7.1 Hz), 2.40 (3H, s), 3.53 (2H, s), 5.02 (1H, quint, J = 7.1 Hz), 5.25 (1H, br), 6.52 (1H, br), 7.22-7.32 (7H, m), 7.70 (2H, d, J = 8.3 Hz)
融点:92-93℃
1H-NMR (400 MHz, CDCl3): δ 3.71 (2H, d, J = 5.4 Hz), 4.30 (2H, s), 4.69 (1H, br), 5.15 (2H, s), 7.30-7.42 (10H, m)
Helv. Chim. Acta, 1996, 79, 1843-1862.
1H-NMR (400 MHz, CDCl3): δ 2.32 (3H, s), 2.41 (3H, s), 3.58 (2H, d, J = 5.9 Hz), 4.35 (2H, d, J = 5.6 Hz), 5.07 (1H, br), 6.42 (1H, br), 7.10 (2H, d, J = 7.2 Hz), 7.12 (2H, d, J = 7.2 Hz), 7.29 (2H, d, J = 8.2 Hz), 7.71 (2H, d, J = 8.2 Hz)
融点:207-208℃(再結晶溶媒:アセトン)
1H-NMR (400 MHz, CDCl3): δ 2.44 (3H, s), 3.61 (2H, d, J = 6.1 Hz), 4.38 (2H, d, J = 6.3 Hz), 5.03 (1H, br), 6.61 (1H, br), 7.12 (2H, d, J = 8.3 Hz), 7.32 (2H, d, J = 8.3 Hz), 7.45 (2H, d, J = 8.3 Hz), 7.73 (2H, d, J = 8.3 Hz)
融点:123-124℃
1H-NMR (400 MHz, CDCl3): δ 2.42 (3H, s), 3.58 (2H, d, J = 6.3 Hz), 4.40 (2H, d, J = 5.9 Hz), 5.01 (1H, br), 6.60 (1H, br), 7.16 (1H, t, J = 8.1 Hz), 7.22 (1H, dd, J = 8.1, 1.5 Hz), 7.23-7.24 (1H, m), 7.30 (2H, d, J = 8.2 Hz), 7.70 (2H, d, J = 8.2 Hz)
Yingyong Huaxue, 1991, 8, 48-51.
Indian J. Chem. Sect. B, 2002, 41B, 2635-2641.
1H-NMR (400 MHz, CDCl3): δ 3.74 (2H, d, J = 6.1 Hz), 5.22 (1H, br), 7.20 (1H, t, J = 8.1 Hz), 7.26-7.30 (1H, m), 7.37 (1H, d, J = 8.1 Hz), 7.54 (2H, d, J = 8.5 Hz), 7.74 (1H, s), 7.84 (2H, d, J = 8.5 Hz), 7.93 (1H, br)
1H-NMR (400 MHz, CDCl3): δ 3.78 (2H, d, J = 6.1 Hz), 5.28 (1H, br), 7.23 (1H, t, J = 8.0 Hz), 7.21-7.33 (3H, m), 7.41 (1H, d, J = 8.0 Hz), 7.78 (1H, s), 7.96 (2H, dd, J = 8.7, 4.8 Hz), 8.04 (1H, br)
1H-NMR (400 MHz, CDCl3): δ 3.70 (2H, d, J = 6.6 Hz), 3.88 (3H, s), 5.12 (1H, br), 7.01 (2H, d, J = 8.9 Hz), 7.19 (1H, t, J = 8.1 Hz), 7.26-7.28 (1H, m), 7.39 (1H, d, J = 8.1 Hz), 7.73 (1H, s), 7.83 (2H, d, J = 8.9 Hz), 8.16 (1H, br)
1H-NMR (400 MHz, CDCl3): δ 3.70 (2H, d, J = 6.6 Hz), 3.87 (3H, s), 5.14 (1H, br), 7.01 (2H, d, J = 8.8 Hz), 7.29 (2H, d, J = 8.9 Hz), 7.45 (2H, d, J = 8.9 Hz), 7.82 (2H, d, J = 8.8 Hz), 8.18 (1H, br)
1H-NMR (400 MHz, CDCl3): δ 3.74 (2H, d, J = 6.3 Hz), 5.19 (1H, br), 7.22-7.32 (4H, m), 7.44 (2H, d, J = 8.8 Hz), 7.92 (2H, dd, J = 9.0, 4.9 Hz), 7.98 (1H, br)
Indian J. Exp. Biol., 1966, 4, 190-1.
1H-NMR (400 MHz, CDCl3): δ 3.83 (2H, d, J = 6.1 Hz), 5.27 (1H, br), 7.02 (1H, t, J = 7.9 Hz), 7.22 (2H, t, J = 8.5 Hz), 7.32 (1H, t, J = 7.9 Hz), 7.55 (1H, d, J = 7.9 Hz), 7.94 (2H, dd, J = 8.5, 5.1 Hz), 8.23 (1H, d, J = 7.9 Hz), 8.37 (1H, br)
[DR-29]
1H-NMR (400 MHz, CDCl3): δ 3.83 (2H, d, J = 6.1 Hz), 5.43 (1H, br), 7.02 (1H, t, J = 8.1 Hz), 7.31 (1H, t, J = 8.1 Hz), 7.51 (2H, d, J = 8.7 Hz), 7.54 (1H, d, J = 8.1 Hz), 7.85 (2H, d, J = 8.7 Hz), 8.21 (1H, d, J = 8.1 Hz), 8.37 (1H, br)
その後反応液に0℃にて飽和重曹水を水層が塩基性を示すまで加える。
水層に塩化メチレンを加え、抽出した有機層を炭酸カリウムで乾燥し、ろ過する。
溶媒を留去すれば、無色結晶の2-アミノ-N-(3-ブロモフェニル)アセトアミド(421mg,収率:84%)を得る。
溶媒を留去した残渣をシリカゲルカラムクロマトグラフィー(15g,ヘキサン:アセトン=6:1~4:1)にて精製すれば、無色結晶のN-(3-ブロモフェニル)-2-フェニルメタンスルフォニルアミノ-アセタミド(41mg,DR-12)を得る。
融点:215-216℃(再結晶溶媒:トルエン)
1H-NMR (400 MHz, CDCl3): δ 3.69 (2H, d, J = 6.3 Hz), 4.38 (2H, s), 4.84 (1H, br), 7.17-7.27 (3H, m), 7.35-7.45 (5H, m), 7.75 (1H, s), 7.80 (1H, br)
融点:200-201℃
1H-NMR (400 MHz, CDCl3): δ 3.69 (2H, d, J = 6.3 Hz), 4.38 (2H, s), 4.84 (1H, br), 7.42-7.52 (9H, m), 7.81 (1H, br)
1H-NMR (400 MHz, CDCl3): δ 3.67 (2H, d, J = 6.3 Hz), 4.36 (2H, s), 4.84 (1H, br), 7.10 (1H, d, J = 7.6 Hz), 7.20-7.32 (2H, m), 7.35-7.45 (5H,m), 7.60 (1H, s), 7.81 (1H, br)
Yingyong Huaxue, 1991, 8, 48-51.
Yingyong Huaxue, 1991, 8, 48-51.
1H-NMR (400 MHz, CDCl3): δ 2.43 (3H, s), 3.70 (2H, d, J = 5.9 Hz), 5.04 (2H, s), 5.19 (1H, br), 6.93 (2H, d, J = 8.8 Hz), 7.34-7.43 (9H, m), 7.77 (2H, d, J = 8.1 Hz), 7.93 (1H, br)
1H-NMR (400 MHz, CDCl3): δ 2.34 (3H, s), 3.63 (2H, s), 4.36 (2H, d, J = 5.9 Hz), 6.25 (1H, br), 7.10 (2H, d, J = 8.2 Hz), 7.14 (2H, d, J = 8.2 Hz), 7.15-7.21 (3H, m), 7.87 (2H, dd, J = 8.7, 5.0 Hz)
反応液をセライトろ過後、溶媒を留去すれば、無色結晶の2-アミノ-N’-(2-(4-フルオロフェニル)アセチル)アセトヒドラジド(233mg,収率100%)を得る。
溶媒を留去した残渣をシリカゲルカラムクロマトグラフィー(15g,ヘキサン:アセトン=2:1~1.5:1)にて精製しすれば、無色結晶のN-(2-{N’-[2-(4-フルオロフェニル)アセチル]ヒドラジノ}-2-オキソエチル)-4-メチル-ベンゼンスルフォナミド(82mg,DR-19)を得る。
1H-NMR (400 MHz, CDCl3): δ 2.44 (3H, s), 3.59 (2H, s), 4.81 (2H, s), 7.05 (2H, t, J = 8.7 Hz), 7.10 (1H, br), 7.10-7.26 (4H, m), 7.36 (2H, d, J = 8.2 Hz), 7.72 (2H, d, J = 8.2 Hz)
その後反応液0℃にて飽和重曹水を水層が塩基性を示すまで加え、塩化メチレンで抽出した有機層を炭酸カリウムで乾燥し、ろ過後溶媒を留去し、アミン体(98mg,98%)を無色結晶物質として得た。
(2)アルゴンガス雰囲気下、アミン体 (98mg,0.43mmol)の塩化メチレン(5mL)溶液にトリエチルアミン(0.12mL,0.86mmol)、0℃にてスルホニルクロライド体(102mg,0.47mmol)を順次加え、室温で終夜撹拌した。
溶媒を留去した残渣をシリカゲルカラムクロマトグラフィー(15g,Hexane:Acetone =8:1~5:1)にて精製しN-(2-ブロモ-フェニル)-2-(2-トリル-エタンスルホニルアミノ)-アセタミド(DR-30)の無色結晶75mg(収率43%)を得た。
融点:132-133℃
1H-NMR (400 MHz, CDCl3): δ 2.41 (3H, s), 3.74 (2H, d, J = 4.4 Hz), 4.39 (2H, d, J = 5.9 Hz), 5.07 (1H, br), 6.58 (1H, br), 6.66 (1H, d, J = 15.5 Hz), 7.09 (2H, d, J = 8.1 Hz), 7.23 (2H, d, J = 7.8 Hz), 7.36-7.38 (4H, m), 7.51 (1H, d, J = 15.5 Hz)
融点:200-201℃
1H-NMR (500 MHz, CDCl3): δ 2.39 (3H, s), 3.79 (3H, s), 3.83 (2H, d, J = 4.6 Hz), 5.14 (1H, br), 6.70 (1H, d, J = 15.5 Hz), 6.85 (2H, d, J = 9.2 Hz), 7.21 (2H, d, J = 8.0 Hz), 7.37-7.39 (4H, m),7.52 (1H, d, J = 15.5 Hz), 7.93 (1H, br)
融点:145-146℃
1H-NMR (500 MHz, CDCl3): δ 2.39 (3H, s), 3.83 (2H, d, J = 6.3 Hz), 5.22 (1H, br), 6.69 (1H, d, J = 15.2 Hz), 7.21 (2H, d, J = 8.0 Hz), 7.36 (2H, d, J = 8.0 Hz), 7.39-7.43 (4H, m), 7.51 (1H, d, J = 15.2 Hz), 8.19 (1H, br)
融点: 216-219 ℃
1H-NMR (500 MHz, CDCl3): δ 2.40 (3H, s), 3.73 (2H, d, J = 6.3 Hz), 4.44 (2H, d, J = 6.3 Hz), 5.01 (1H, br), 6.58 (1H, br), 6.65 (1H, d, J = 15.5 Hz), 7.15-7.20 (2H, m), 7.22 (2H, d, J = 8.0 Hz), 7.25-7.30 (1H, m), 7.36 (2H, d, J = 8.0 Hz), 7.47 (1H, d, J = 15.5 Hz); 13C-NMR (125 MHz, DMSO-d6): 21.02, 35.64 (d, J = 4.8 Hz), 44.95, 118.32 (d, J = 23.9 Hz), 119.99 (d, J = 9.6 Hz), 125.46 (d, J = 15.6 Hz), 125.64, 127.28 (d, J = 3.6 Hz), 128.36, 129.54, 130.05, 130.80 (d, J = 4.8 Hz), 139.20, 140.44, 159.73 (d, J = 249.5 Hz), 168.53
融点:161-162 ℃.
1H-NMR (400 MHz, CDCl3): δ 2.36 (3H, s), 3.80 (2H, d, J = 6.1 Hz), 5.00 (2H, s), 5.29 (1H, br), 6.68 (1H, d, J = 15.4 Hz), 6.88 (2H, d, J = 9.0 Hz), 7.17 (2H, d, J = 7.8 Hz), 7.25-7.45 (9H, m), 7.49 (1H, d, J = 15.4 Hz), 8.02 (1H, br)
13C-NMR (125 MHz, DMSO-d6): δ 20.99, 45.59, 69.33, 114.79, 120.80, 125.89, 127.64, 127.77, 128.31, 128.39, 129.51, 130.07, 131.90, 137.13, 139.05, 140.35,
154.38, 166.45
融点:178-179 ℃
溶媒を留去後、飽和重曹水を水層が塩基性を示すまで加え、塩化メチレンで抽出する。
有機層を硫酸ナトリウムで乾燥し、ろ過後溶媒を留去すれば、一般式4aのエチルエステル体を得る。
次いで、溶媒を留去後、一般式2aのイソチオシアネート体(1mmol)の塩化メチレン(5mL)溶液をカニューレを用いて加え、室温で終夜撹拌する。
反応液を吸引ろ過すれば、一般式1aのチオウレア体を得る。
融点:232-233℃(再結晶溶媒:エタノール)
1H-NMR (400 MHz, DMSO-d6): δ 3.85 (2H, s), 6.95-7.01 (3H, m), 7.38 (1H, dd, J = 5.0, 1.3 Hz), 7.53 (2H, d, J = 8.5 Hz), 7.64 (2H, d, J = 8.5 Hz), 7.73 (1H, d, J = 15.9 Hz), 11.16 (1H, br), 11.66 (1H, br), 12.57 (1H, br)
13C-NMR (100 MHz, DMSO-d6): δ 33.90, 120.18, 125.18, 126.65, 126.67, 129.20, 129.90, 132.97, 135.26, 136.19, 143.14, 165.56, 166.26, 176.63
IR (KBr): 3211, 1684, 1655, 1630 cm-1
MS (EI): m/z 379 (M+)
融点:219-220℃(再結晶溶媒:ヘキサン・アセトン)
1H-NMR (400 MHz, DMSO-d6): δ 3.86 (2H, s), 6.95-6.98 (2H, m), 7.14 (1H, d, J = 16.1 Hz), 7.38 (1H, dd, J = 5.0, 1.3 Hz), 7.72 (1H, d, J = 16.1 Hz), 7.81 (2H, s), 11.2 (1H, br), 11.9 (1H, br), 12.5 (1H, br)
13C-NMR (100 MHz, DMSO-d6): δ 33.89, 125.18, 126.63, 126.65, 128.05, 129.00, 130.17, 134.61, 134.88, 136.16, 136.68, 164.59, 166.29, 176.44
IR (KBr): 3196, 1682, 1653, 1624 cm-1
MS (EI): m/z 447 (M+)
融点:222-223℃(再結晶溶媒:ヘキサン・アセトン)
1H-NMR (400 MHz, DMSO-d6) δ: 3.88 (2H, s), 6.97-7.00 (2H, m), 7.17 (1H, d, J = 16.3 Hz ), 7.40 ( 1H, dd, J = 5.1, 1.5 Hz), 7.86 (1H, d, J = 16.3 Hz), 7.89 (2H, d, J = 8.9 Hz), 8.32 (2H, d, J = 8.9 Hz), 11.20 (1H, br), 11.78 (1H, br), 12.56 (1H, br)
13C-NMR (100 MHz, DMSO-d6) δ: 33.89, 123.72, 124.25, 125.19, 126.66, 126.67, 129.25, 136.17, 140.38, 141.79, 148.16, 165.00, 166.28, 176.46
IR (KBr): 3244, 1682, 1655, 1522, 1342 cm-1
MS (EI): m/z 390 (M+)
融点:212-213 ℃(再結晶溶媒:エタノール)
1H-NMR (400 MHz, DMSO-d6): δ 2.33 (3H, s), 3.85 (2H, s), 6.92-6.98 (3H, m), 7.27 (2H, d, J = 7.9 Hz) 7.38 (1H, dd, J = 5.1, 1.0 Hz), 7.51 (2H, d, J = 7.9 Hz), 7.69 (1H, d, J = 15.9 Hz), 11.14 (1H, br), 11.60 (1H, br), 12.59 (1H, br)
13C-NMR (100 MHz, DMSO-d6): δ 21.09, 33.92, 118.26, 125.20, 126.66, 126.69, 128.30, 129.75, 131.32, 136.22, 140.95, 144.69, 165.96, 166.26, 176.69
IR (KBr): 3227, 1684, 1661, 1630 cm-1
MS (EI): m/z 359 (M+)
融点:215-216℃(再結晶溶媒:アセトン)
1H-NMR (400 MHz, DMSO-d6): δ 3.85 (2H, s), 6.93 (1H, d, J = 15.9 Hz), 6.96-6.99 (2H, m), 7.31 (2H, t, J = 8.8 Hz), 7.38 (1H, dd, J = 4.9, 1.5 Hz), 7.69 (2H, dd, J = 8.8, 5.6 Hz), 7.74 (1H, d, J = 15.9 Hz), 11.15 (1H, br), 11.64 (1H, br), 12.58 (1H, br)
13C-NMR (100 MHz, DMSO-d6): δ 33.93, 116.25 (d, J = 22.3 Hz), 119.25, 125.23, 126.69, 126.72, 130.63 (d, J = 8.3 Hz), 130.73 (d, J = 3.3 Hz), 136.22, 143.42, 163.46 (d, J = 248.9 Hz), 165.73, 166.31, 176.78
IR (KBr): 3186, 1680, 1651, 1628 cm-1
MS (EI): m/z 363 (M+)
融点:207-208 ℃(再結晶溶媒:メタノール)
1H-NMR (600 MHz DMSO-d6) δ: 3.82 (3H, s), 3.85 (2H, s), 3.88 (3H, s), 6.62 (2H, m), 6.97 (3H, m), 7.38 (1H, dd, J = 5.1, 1.5 Hz), 7.47 (1H, d, J = 9.5 Hz), 7.81 (1H, d, J = 15.8 Hz), 11.11 (1H, br), 11.56 (1H, br), 12.68 (1H, br)
13C-NMR (150 MHz, DMSO-d6) δ: 33.89, 55.54, 55.72, 98.45, 106.33, 115.42, 116.66, 125.15, 126.61, 126.65, 130.97, 136.22, 140.07, 159.98, 163.05, 166.19, 166.80, 176.94
IR (KBr): 3225, 1670, 1606, 1531, 1215, 1132.1 cm-1
MS (EI): m/z 405 (M+)
融点:212-213℃(再結晶溶媒:ヘキサン・アセトン)
1H-NMR (400 MHz, DMSO-d6): δ 3.85 (2H, s), 6.95-6.98 (2H, s), 7.06 (1H, d, J = 15.9 Hz), 7.38 (1H, dd, J = 4.9, 1.5 Hz), 7.67 (1H, d, J = 15.9 Hz), 7.84 (2H, d, J = 1.5 Hz), 7.92 (1H, d, J = 1.5 Hz), 11.17 (1H, br), 11.59 (1H, br), 12.48 (1H, br)
13C-NMR (100 MHz, DMSO-d6) δ: 33.91, 122.77, 123.13, 125.22, 126.70, 129.69, 129.80, 134.89, 136.19, 138.31, 141.07, 165.00, 166.34, 176.59
IR (KBr): 3184, 1686, 1663, 1632 cm-1
MS (EI): m/z 501 (M+)
融点:201-202℃(再結晶溶媒:酢酸エチル)
1H-NMR(400 MHz, DMSO-d6):δ1.20 (6H, d, J = 6.8 Hz), 2.91 (1H, sept, J = 6.8 Hz), 3.85 (2H, s), 6.93-6.98 (3H, m), 7.34 (2H, d, J = 8.1 Hz), 7.38 (1H, dd, J = 5.0, 1.3 Hz), 7.54 (2H, d, J = 8.1 Hz), 7.70 (1H, d, J = 15.9 Hz), 11.14 (1H, br), 11.62 (1H, br), 12.59 (1H, br)
13C-NMR (100 MHz, DMSO-d6): δ 23.56, 33.40, 33.89, 118.37, 125.18, 126.64, 126.67, 127.12, 128.40, 131.73, 136.20, 144.63, 151.64, 165.92, 166.24, 176.78
MS (EI): m/z 387 (M+)
融点:231-232℃
1H-NMR (400 MHz, DMSO-d6): δ 3.86 (2H, s), 6.96-6.99 (2H, m), 7.04 (1H, d, J = 15.9 Hz), 7.38-7.41 (2H, m), 7.48 (2H, t, J = 7.6 Hz), 7.70-7.80 (7H, m), 11.16 (1H, br), 11.66 (1H, br), 12.61 (1H, br)
13C-NMR (100 MHz, DMSO-d6): δ 33.91, 119.26, 125.19, 126.68, 126.72, 127.30, 128.08, 128.94, 129.05, 131.31, 133.13, 136.21, 139.07, 142.26, 144.13, 165.79, 166.27, 176.74
MS (EI): m/z 421 (M+)
融点:220-221℃(再結晶溶媒:ヘキサン・アセトン)
1H-NMR(400 MHz, DMSO-d6):δ 3.87 (8H, s), 6.71 (2H, d, J = 8.3 Hz), 6.96-6.98 (2H, m), 7.34-7.38 (3H, m), 8.06 (1H, d,J= 15.9 Hz), 11.12 (1H, br), 11.67 (1H, br), 12.73 (1H, br)
13C-NMR (100 MHz, DMSO-d6): δ 33.90, 55.92, 104.07, 110.99, 120.95, 125.18, 126.62, 126.67, 132.55, 135.32, 136.23, 159.82, 166.17, 167.53, 176.86
; IR (KBr): 3219, 1670, 1653, 1611 cm-1
MS (EI): m/z 405 (M+)
融点:207-208℃
1H-NMR(400 MHz, DMSO-d6):δ 3.85 (2H, s), 6.96-6.98 (2H, m), 7.20 (1H, d, J = 16.0 Hz), 7.36-7.40 (3H, m), 7.60 (1H, d, J= 16.0Hz), 11.17 (1H, br), 11.87 (1H, br), 12.57 (1H, br)
13C-NMR (100 MHz, DMSO-d6): δ 33.90, 101.73 (td, J = 26.9, 2.5 Hz), 108.66 (td, J = 15.3, 5.0 Hz), 124.64 (td, J = 8.4, 3.0 Hz), 125.19, 126.65, 126.68, 129.11, 136.19, 161.35 (dt, J = 254.7, 7.9 Hz), 161.42 (dt, J = 254.7, 8.1 Hz), 165.39, 166.27, 176.44
IR (KBr): 3190, 1684, 1653, 1624 cm-1
MS (EI): m/z 399 (M+)
融点:212-213℃
1H-NMR (400 MHz, DMSO-d6) δ: 3.62 (2H, s), 6.93 (1H, d, J = 15.7 Hz ), 7.25-7.32 (7H, m), 7.69 (2H, dd, J = 8.8, 5.6 Hz), 7.73 (1H, d, J = 15.7 Hz), 11.10 (1H, s), 11.62 (1H, s), 12.56 (1H, s)
13C-NMR (100 MHz, DMSO-d6) δ: 39.57, 116.20 (d, J = 21.5 Hz ), 119.25, 126.61, 128.25, 129.20, 130.57 (d, J = 9.1 Hz ), 130.71 (d, J = 3.3 Hz),135.26, 143.33, 163.41 (d, J = 248.9 Hz), 165.66, 167.29, 176.77
MS(EI): m/z 357 (M+)
融点:224-225℃
1H-NMR (400 MHz, DMSO-d6): δ 3.86 (2H, s), 6.95-6.99 (2H, m), 7.11 (1H, d, J = 15.9 Hz), 7.38 (1H, dd, J = 4.9, 1.5 Hz), 7.76-7.83 (5H, m), 11.17 (1H, br), 11.72 (1H, br), 12.53 (1H, br)
13C-NMR (100 MHz, DMSO-d6): δ 33.93, 122.34, 124.00 (q, J = 272.4 Hz), 125.22, 126.02 (q, J = 4.1 Hz), 126.70, 127.83, 128.86, 130.24 (q, J = 32.0 Hz), 136.19, 138.03 (q, J = 1.7 Hz), 142.66, 165.28, 166.34, 176.62
IR (KBr): 1636, 1661, 1684, 3196 cm-1
MS (EI): m/z 413 (M+)
融点:210-211℃
1H-NMR (400 MHz, DMSO-d6) δ: 3.62 (2H, s), 7.19 (1H, d, J = 16.1 Hz), 7.23-7.40 (7H, m), 7.59 (1H, d, J = 16.1 Hz), 11.13 (1H, br), 11.86 (1H, br), 12.53 (1H, br)
13C-NMR (100 MHz, DMSO-d6) δ: 39.54, 101.72 (td, J = 27.3, 3.3 Hz), 108.64 (td, J = 16.1, 4.1 Hz), 124.67, 126.60, 128.25, 129.07, 129.18, 135.25, 160.01 (dd, J = 12.8, 9.9 Hz), 162.63 (dd, J = 12.8, 9.9 Hz), 165.35, 167.28, 176.47
MS (EI): m/z 393 (M+)
融点:192-193℃
1H-NMR (400 MHz, DMSO-d6) δ: 3.62 (2H, s), 7.06 (1H, d, J = 15.9 Hz), 7.23-7.32 (5H, m), 7.66 (1H, d, J = 15.9 Hz), 7.84 (2H, s), 7.92 (1H, s), 11.13 (1H, br), 11.57 (1H, br), 12.47 (1H, br)
13C-NMR (100 MHz, DMSO-d6) δ: 39.59, 122.79, 123.12, 126.66, 128.30, 129.24, 129.80, 134.88, 135.26, 138.32, 141.06, 164.99, 167.42, 176.69
MS (EI): m/z 495 (M+)
融点:217-218℃
1H-NMR (400 MHz, DMSO-d6) δ: 6.98 (1H, d, J = 15.7 Hz), 7.21 (1H, t, J = 4.5 Hz), 7.32 ( 2H, t, J = 8.7 Hz) , 7.69-7.72 ( 2H, m ), 7.77 (1H, d, J = 15.7 Hz), 7.87 (1H, d, J = 4.5 Hz), 7.90 (1H, d, J = 4.5 Hz), 11.10 (1H, br), 11.67 (1H, br), 12.14 (1H, br)
13C-NMR (100 MHz, DMSO-d6) δ: 116.24 (d, J = 22.3 Hz), 119.41, 128.21, 129.60, 130.63 (d, J = 9.1 Hz), 130.76 (d, J = 3.3 Hz), 132.00, 136.63, 143.47, 159.48, 163.45 (d, J = 248.9 Hz), 165.44, 177.93
MS (EI): m/z 349 (M+)
融点:211-212℃
1H-NMR (400 MHz, DMSO-d6) δ: 3.62 (2H, s), 3.89 (6H, s), 6.71 (2H, d, J = 8.3 Hz), 7.25-7.39 (7H, m), 8.05 (1H, d, J = 15.9 Hz), 11.07 (1H, s) , 11.65 (1H, s), 12.70 (1H, br)
13C-NMR (100 MHz, DMSO-d6) δ: 39.59, 55.94, 104.09, 111.02, 121.00, 126.63, 128.29, 129.21, 132.57, 135.19, 135.31, 159.84, 167.26, 167.53, 177.00
MS (EI): m/z 399 (M+)
融点:209-210℃
1H-NMR (400 MHz, DMSO-d6): δ 3.88 (6H, s), 6.72 (2H, d, J = 8.5 Hz), 7.21 (1H, t, J = 5.1 Hz), 7.37-7.42 (2H, m), 7.84-7.90 (2H, m), 8.09 (1H, d, J = 15.9 Hz), 11.07 (1H, br), 11.68 (1H, br), 12.14 (1H, br)
MS (EI): m/z 391 (M+)
融点:217-218℃
1H-NMR (400 MHz, DMSO-d6) δ: 7.11 (1H, d, J = 15.6 Hz), 7.21 (1H, t, J = 4.3 Hz), 7.70 ( 1H, d, J = 15.6 Hz), 7.86-7.93 (5H, m), 11.11 (1H, br), 11.62 (1H, br), 12.06 (1H, br); 13C-NMR (100 MHz, DMSO-d6) δ: 122.90, 123.11, 128.20, 129.62, 129.80, 132.022, 134.88, 136.59, 138.33, 141.16, 159.51, 164.73, 181.07
MS (EI): m/z 487 (M+)
融点:195-196℃
1H-NMR (400 MHz, DMSO-d6) δ: 3.61 (2H, s), 7.06 (1H, d, J = 16.0 Hz), 7.11-7.35 (4H, m), 7.66 (1H, d, J = 16.0 Hz), 7.84 (2H, s), 7.92 (1H, s), 11.11 (1H, br), 11.56 (1H, br), 12.44 (1H, br)
13C-NMR (100 MHz, DMSO-d6) δ: 30.88, 115.05 (d, J = 21.5 Hz), 122.79, 123.16 (d, J = 2.5 Hz), 128.35, 129.28, 129.78, 129.86, 131.11, 134.98 (d, J = 8.3 Hz), 139.75 (d, J = 282.9 Hz), 151.38, 176.13, 180.47
MS (EI): m/z 515 (M+)
融点:224-225℃
1H-NMR (400 MHz, DMSO-d6) δ: 7.11 (1H, d, J = 15.7 Hz), 7.52 (2H, t, J = 7.4 Hz), 7.60 (1H, t, J = 7.4 Hz), 7.71 (1H, d, J = 15.7 Hz), 7.87 (2H, s), 7.90 (2H, d, J = 7.4 Hz), 7.93 (1H, s), 11.10 (1H, br), 11.63 (1H, br), 12.18 (1H, br)
13C-NMR (100 MHz, DMSO-d6) δ: 122.89, 123.12, 127.65, 128.51, 129.80, 132.02, 132.10, 134.88, 138.33, 141.13, 164.56, 164.83, 180.46
融点:203-204℃
1H-NMR (400 MHz, DMSO-d6) δ: 2.28 (3H, s), 3.57 (2H, s), 7.04-7.20 (5H, m), 7.66 ( 1H, d, J= 15.9 Hz), 7.84 (2H, s), 7.91 (1H, s), 11.10 (1H, br), 11.55 (1H, br), 12.48 (1H, br)
13C-NMR (100 MHz, DMSO-d6) δ: 20.97, 122.78, 123.12, 126.29, 127.26, 128.18, 129.79, 129.84, 134.88, 135.11, 137.31, 138.31, 141.04, 164.97, 167.40, 176.58
融点:202-203℃
1H-NMR (400 MHz, DMSO-d6) δ: 3.58 (2H, s), 3.74 (3H, s), 6.81 (1H, d, J = 7.9 Hz), 6.89 (1H, d, J = 7.9 Hz), 6.92 (1H, s), 7.06 (1H, d, J = 16.0 Hz), 7.21 (1H, t, J = 7.9 Hz), 7.67 (1H, d, J = 16.0 Hz), 7.83-7.84 (2H, m), 7.92 (1H, s), 11.10 (1H, br), 11.56 (1H, br), 12.45 (1H, br)
13C-NMR (100 MHz, DMSO-d6) δ: 39.63, 54.98, 112.17, 114.82, 121.48, 122.78, 123.11, 129.27, 129.78, 134.87, 136.69, 138.30, 141.02, 159.16, 164.95, 167.23, 176.72
融点:213-214℃
1H-NMR (400 MHz, DMSO-d6) δ: 2.57 (2H, t, J = 7.8 Hz), 2.87 (2H, t, J = 7.8 Hz), 7.06 (1H, d, J = 16.0 Hz), 7.18-7.28 (5H, m), 7.67 (1H, d, J = 16.0 Hz), 7.84 (2H, d, J = 1.5 Hz), 7.92 (1H, t, J = 1.5 Hz), 10.98 (1H, br), 11.54 (1H, br), 12.47 (1H, br)
13C-NMR (100 MHz; DMSO-d6) δ: 30.57, 34.46, 122.80, 123.10, 125.99, 128.22, 128.30, 129.76, 132.25, 138.30, 140.80, 154.67, 168.68, 176.29, 180.24
MS (EI): m/z 511 (M+)
溶媒を留去後、飽和重曹水を水層が塩基性を示すまで加え、塩化メチレンで抽出する。
有機層を硫酸ナトリウムで乾燥し、ろ過後溶媒を留去すれば、一般式5aのエチルエステル体を得る。
次いで、溶媒を留去後、一般式2bのイソチオシアネート体(1mmol)の塩化メチレン(5mL)溶液をカニューレを用いて加え、室温で終夜撹拌する。
反応液を吸引ろ過すれば、一般式1bのチオウレア体を得る。
融点:161-162℃
1H-NMR (400 MHz, DMSO-d6) δ: 3.74 (2H, s), 3.81 (2H, s), 6.93-6.95 (2H, m), 7.24-7.37 (6H, m), 11.06 (1H, br), 11.73 (1H, br), 12.30 (1H, br)
13C-NMR (100 MHz, DMSO-d6) δ: 33.94, 42.11, 125.24, 126.70, 126.74, 127.08, 128.32, 128.51, 129.41, 134.30, 166.39, 167.43, 176.90
MS (EI): m/z 333 (M+)
融点:182-183℃
1H-NMR (400 MHz, DMSO-d6) δ: 3.57 (2H, s), 3.74 (2H, s), 7.11 (2H, t, J = 8.7 H), 7.20-7.40 (7H, m), 10.10 (1H, br), 11.02 (1H, br), 11.73 (1H, br)
13C-NMR (100 MHz, DMSO-d6) δ: 38.64, 42.07, 114.85 (d, J = 21.5 Hz), 126.51, 127.01, 128.23, 128.45, 129.04, 129.37, 131.06 (d, J = 8.3 Hz), 131.43 (d, J = 2.5 Hz), 135.01 (d, J = 286.9 Hz), 167.33, 172.57, 177.11
融点:149-150℃
1H-NMR (400 MHz, DMSO-d6) δ: 2.26 (3H, s), 3.53 (2H, s), 3.74 (2H, s), 7.09-7.29 (9H, m) , 11.01 (1H, br), 11.72 (1H, br), 12.28 (1H, br)
融点:174-175℃
1H-NMR (400 MHz, DMSO-d6) δ: 3.67 (2H, s), 3.74 (2H, s), 7.07 (2H, t, J = 7.4 Hz), 7.22-7.40 (6H, m), 11.07 (1H, br), 11.73 (1H, br), 12.23 (1H, br)
融点:178-179℃
1H-NMR (400 MHz, DMSO-d6) δ: 3.74 (2H, s), 4.03 (2H, s), 7.03-7.12 (3H, m), 7.23-7.34 (5H, m), 11.02 (1H, br), 11.74 (1H, br), 12.18 (1H, br)
13C-NMR (100 MHz, DMSO-d6) δ: 26.73, 42.06, 110.77 (d, J = 20.7 Hz), 111.26 (d, J = 25.6 Hz), 127.00, 128.44, 129.35, 134.29, 159.86 (d, J = 8.3 Hz), 162.31 (d, J = 6.3 Hz), 165.60, 172.53, 177.32
融点:88-90℃
1H-NMR (400 MHz, DMSO-d6) δ: 2.52 (2H, m), 2.83 (2H, m), 3.74 (2H, s), 7.16-7.30 (10H, m), 10.80 (1H, br), 11.70 (1H, br), 12.28 (1H, br)
MS (EI): m/z 341 (M+)
融点:178-179℃
1H-NMR (400 MHz, DMSO-d6) δ: 3.57 (2H, s), 3.74 (2H, s), 7.12-7.32 (8H, m), 11.03 (1H, br), 11.72 (1H, br), 12.28 (1H, br)
13C-NMR (100 MHz, DMSO-d6) δ: 38.60, 41.08, 115.03 (t, J = 20.3 Hz), 128.22, 129.15, 130.38 (d, J = 2.5 Hz), 131.01 (d, J = 7.9 Hz), 131.32 (d, J = 7.9 Hz), 161.32 (d, J = 242.3 Hz), 167.24, 172.38, 176.98
MS (EI): m/z 363 (M+)
融点:186-187℃
1H-NMR (400 MHz, DMSO-d6) δ: 3.57 (2H, s), 3.88 (2H, s), 7.08-7.14 (4H, m), 7.30-7.40 (3H, m), 11.03 (1H, br), 11.86 (1H, br), 12.09 (1H, br)
13C-NMR (100 MHz, DMSO-d6) δ: 29.27, 30.70, 38.62, 111.34 (dd, J = 5.8, 19.0 Hz), 114.95 (d, J = 20.7 Hz), 129.83 (t, J = 10.3 Hz), 131.03 (d, J = 8.3 Hz), 131.40 (d, J = 3.3 Hz), 159.81 (t, J = 10.3 Hz), 162.25 (t, J = 8.3 Hz), 167.31, 170.28, 176.85
MS(EI): m/z 381 (M+)
溶媒を留去後、飽和重曹水を水層が塩基性を示すまで加え、塩化メチレンで抽出する。
有機層を硫酸ナトリウムで乾燥し、ろ過後溶媒を留去すれば、一般式4aのエチルエステル体を得る。
次いで、溶媒を留去後、一般式2cのイソチオシアネート体(1mmol)の塩化メチレン(5mL)溶液をカニューレを用いて加え、室温で終夜撹拌する。反応液を吸引ろ過すれば、一般式1cのチオウレア体を得る。
融点:132-133℃
1H-NMR (400 MHz, DMSO-d6) δ: 0.93-1.92 (5H, m), 2.27 (2H, d, J = 6.8 Hz), 3.58 (2H, s), 7.13 (2H, t, J= 8.8 Hz), 7.30-7.40 (2H, m), 11.04 (1H, br), 11.46 (1H, br), 12.42 (1H, br)
13C-NMR (100 MHz, DMSO-d6) δ: 24.48, 25.66, 32.24, 34.55, 38.60, 42.93, 114.96 (d, J = 21.5 Hz), 131.04 (d, J = 8.3 Hz), 131.43 (d, J = 2.5 Hz), 163.90 (d, J = 282.9 Hz), 167.33, 174.15, 176.75
MS(EI): m/z 351 (M+)
1H-NMR (500 MHz, DMSO-d6) δ: 3.57 (2H, s), 3.98 (2H, s), 6.96-7.00 (2H, m), 7.12 (2H, t, J = 8.7 Hz), 7.33 (2H, dd, J = 8.7, 5.7 Hz), 7.41 (1H, dd, J = 3.8, 2.6 Hz), 11.03 (1H, br), 11.74 (1H, br), 12.18 (1H, br)
1H-NMR (500 MHz, DMSO-d6) δ: 2.72 (2H, t, J = 7.5 Hz), 2.83 (2H, t, J = 7.5 Hz), 3.58 (2H, s), 7.13 (2H, t, J = 9.0 Hz), 7.17 (1H, td, J = 7.4, 1.7 Hz), 7.21 (2H, dd, J = 7.4, 1.7 Hz), 7.27 (2H, td, J = 7.4, 1.7 Hz), 7.34 (2H, dd, J = 9.0, 5.6 Hz), 11.02 (1H, br), 11.52 (1H, br), 12.33 (1H, br)
溶媒を留去した残渣をシリカゲルカラムクロマトグラフィー(15g,ヘキサン:アセトン=10:1~1:1)にて精製すれば、無色結晶の4-メチル-N-[2-(3-フェニルウレイド)エチル]ベンゼンスルホニルアミドを89mg(収率57%)で得た。
13C-NMR (125 MHz, DMSO-d6): δ 20.92, 38.82, 42.82, 117.65, 121.05, 126.55, 128.62, 129.63, 137.30, 140.40, 142.64, 155.15
IR (KBr): 1161, 1325, 1593, 1645, 3302 cm-1
MS (EI): m/z 333 (M+)
融点:154-155℃(再結晶溶媒:トルエン)
1H-NMR (400 MHz, CDCl3): δ 2.40 (3H, s), 3.07 (2H, t, J = 4.8 Hz), 3.35 (2H, t, J = 4.8 Hz), 5.12 (1H, br), 5.33 (1H, br), 6.45 (1H, br), 6.97 (2H, t, J = 8.2 Hz), 7.24-7.29 (4H, m), 7.72 (2H, d, J = 7.8 Hz)
13C-NMR (125 MHz, DMSO-d6): δ 20.92, 38.88, 42.81, 115.07 (d, J = 21.6 Hz), 119.27 (d, J = 8.4 Hz), 126.56, 129.64, 136.78 (d, J = 2.4 Hz), 137.33, 142.65, 155.22, 156.91 (d, J = 237.5 Hz)
IR (KBr): 1165, 1323, 1508, 1645, 3314 cm-1
MS (EI): m/z 351 (M+)
融点:161-162℃(再結晶溶媒:トルエン)
1H-NMR (400 MHz, CDCl3): δ 2.40 (3H, s), 3.07 (2H, t, J = 4.9 Hz), 3.37 (2H, t, J = 4.9 Hz), 5.52 (2H, m), 7.01 (1H, br), 7.10 (1H, dd, J = 8.7, 2.4 Hz), 7.22-7.27 (1H, m), 7.28 (2H, d, J = 8.1 Hz), 7.48 (1H, d, J = 2.4 Hz), 7.71 (2H, d, J = 8.1 Hz)
13C-NMR (125MHz, DMSO-d6): δ 20.89, 38.90, 42.56, 117.68, 118.66, 122.24, 126.54, 129.61, 130.37, 130.90, 137.30, 140.65, 142.61, 154.76
IR (KBr): 1157, 1319, 1541, 1674, 3393 cm-1
MS (EI): m/z 401 (M+)
融点:154-155℃
1H-NMR (400 MHz, CDCl3): δ 2.39 (3H, s), 3.10 (2H, t, J = 5.6 Hz), 3.37 (2H, t, J = 5.6 Hz), 3.85 (3H, s), 5.10 (1H, br), 5.33 (1H, br), 6.80 (1H, br), 6.86 (1H, dd, J = 7.8, 1.6 Hz), 6.94 (1H, td, J = 7.8, 1.6 Hz), 7.01 (1H, td, J = 7.8, 1.6 Hz), 7.25-7.27 (2H, m), 7.74 (2H, d, J = 8.3 Hz), 7.92 (1H, dd, J = 7.8, 1.6 Hz)
13C-NMR (125MHz, DMSO-d6): δ 20.92, 38.86, 42.94, 55.61, 110.53, 118.04, 120.45, 121.04, 126.58, 129.38, 129.63, 137.34, 142.65, 147.34, 155.22
IR (KBr): 1155, 1321, 1572, 1647, 3277 cm-1
MS (EI): m/z 363 (M+)
融点:184-185℃
1H-NMR (400 MHz, CDCl3): δ 2.41 (3H, s), 3.20 (2H, t, J = 5.5 Hz), 3.78 (2H, t, J = 5.5 Hz), 3.88 (3H, s), 6.49 (1H, br), 6.99-7.03 (2H, m), 7.26-7.30 (5H, m), 7.59 (1H, br), 7.71 (2H, d, J = 8.3 Hz)
13C-NMR (125 MHz, CDCl3): δ 21.43, 42.43, 44.48, 55.74, 111.97, 121.10, 124.93, 125.40, 126.95, 127.80, 129.71, 136.40, 143.50, 152.46, 180.92
MS (EI): m/z 379 (M+)
1H-NMR (400 MHz, CDCl3): δ 2.38 (3H, s), 3.04 (2H, t, J = 5.1 Hz), 3.33 (2H, t, J = 5.1 Hz), 3.74 (3H, s), 6.58 (1H, d, J = 7.8 Hz), 6.78 (1H, d, J = 7.8 Hz), 6.99 (1H, s), 7.05 (1H, br), 7.13 (1H, t, J = 7.8 Hz), 7.20-7.30 (2H, m), 7.72 (2H, d, J = 8.3 Hz)
13C-NMR (125 MHz, DMSO-d6): δ 20.92, 38.83, 42.82, 54.82, 103.47, 106.47, 110.04, 126.56, 129.37, 129.65, 137.32, 141.66, 142.66, 155.10, 159.65
IR (KBr): 1163, 1329, 1560, 1655, 3350 cm-1
MS (EI): m/z 363 (M+)
融点:136-137℃
1H-NMR (400 MHz, CDCl3): δ 1.45 (3H, t, J = 7.1 Hz), 2.39 (3H, s), 3.11 (2H, t, J = 5.4 Hz), 3.38 (2H, t, J = 5.4 Hz), 4.09 (2H, q, J = 7.1 Hz), 6.88 (1H, d, J = 7.1 Hz), 6.93 (1H, t, J = 7.1 Hz), 7.00 (1H, t, J = 7.1 Hz), 7.26-7.31 (2H, m), 7.51 (1H, br), 7.74 (2H, d, J = 8.1 Hz), 7.88 (1H, d, J = 7.1 Hz)
13C-NMR (125 MHz, DMSO-d6): δ 14.68, 20.92, 38.86, 42.89, 63.81, 111.56, 118.04, 120.36, 121.00, 126.56, 129.55, 129.63, 137.30, 142.64, 146.39, 155.12
MS (EI): m/z 377 (M+)
融点:129-130℃
1H-NMR (400 MHz, CDCl3): δ 2.39 (3H, s), 3.11 (2H, t, J = 4.8 Hz), 3.37 (2H, t, J = 4.8 Hz), 5.11 (1H, br), 5.33 (1H, br), 6.73 (1H, br), 7.18-7.32 (4H, m), 7.72 (2H, d, J = 7.8 Hz), 8.08 (1H, d, J = 8.8 Hz)
13C-NMR (125 MHz, DMSO-d6): δ 20.91, 38.92, 42.62, 121.55, 121.78, 125.17, 126.56, 127.44, 128.36, 129.61, 135.89, 137.28, 142.63, 154.61
MS (EI): m/z 401 (M+)
融点:161-162℃(再結晶溶媒:トルエン)
1H-NMR (400 MHz, CDCl3): δ 2.26 (3H, s), 2.37 (3H, s), 3.03 (2H, t, J = 5.0 Hz), 3.32 (2H, t, J = 5.0 Hz), 6.84 (1H, d, J = 7.6 Hz), 7.02 (1H, d, J = 7.6 Hz), 7.07 (1H, br), 7.12 (1H, t, J = 7.6 Hz), 7.24-7.30 (5H, m), 7.71 (2H, d, J = 8.1 Hz)
13C-NMR (125 MHz, DMSO-d6): δ 20.96, 21.26, 38.81, 42.86, 114.89, 118.25, 121.84, 126.57, 128.47, 129.62, 137.33, 137.71, 140.30, 142.67, 155.18
融点:114-115 ℃(再結晶溶媒:トルエン).
1H-NMR (400 MHz, CDCl3): δ 2.26 (3H, s), 2.40 (3H, s), 3.14 (2H, t, J = 4.8 Hz), 3.73 (2H, t, J = 4.8 Hz), 4.14 (1H, br), 6.16 (1H, br), 7.13-7.26 (5H, m), 7.27 (2H, d, J = 7.8 Hz), 7.68 (2H, d, J = 7.8 Hz)
13C-NMR (125 MHz, DMSO-d6): δ 17.68, 21.03, 40.03, 41.71, 126.34, 126.49, 127.71, 129.67, 129.69, 130.69, 134.73, 136.72, 137.33, 142.67, 181.13
融点:131-132℃
1H-NMR (400 MHz, CDCl3): δ 2.29 (3H, s), 2.39 (3H, s), 3.19 (2H, t, J = 5.1 Hz), 3.75 (2H, t, J = 5.1 Hz), 3.82 (3H, s), 6.86 (1H, d, J = 7.3 Hz), 7.00-7.15 (2H, m), 7.20-7.26 (3H, m), 7.27 (2H, d, J = 8.1 Hz), 7.70 (2H, d, J = 8.1 Hz)
13C-NMR (125 MHz, DMSO-d6): δ 20.27, 20.96, 41.71, 43.32, 55.60, 111.53, 126.26, 126.41, 126.57, 126.80, 128.78, 129.69, 137.33, 142.67, 149.99, 180.59
融点:130-131℃
1H-NMR (400 MHz, CDCl3): δ 2.40 (3H, s), 3.18 (2H, t, J = 5.1 Hz), 3.79 (2H, t, J = 5.1 Hz), 6.63 (1H, br), 7.20-7.27 (3H, m), 7.28 (2H, d, J = 7.6 Hz), 7.34 (1H, t, J = 7.4 Hz), 7.40-7.52 (2H, m), 7.70 (2H, d, J = 7.6 Hz)
13C-NMR (125 MHz, CDCl3): δ 21.45, 42.28, 44.65, 126.91, 127.59, 127.90, 128.05, 129.71, 129.73, 130.34, 133.54, 136.14, 143.69, 181.16
1H-NMR (400 MHz, CDCl3): δ 3.07 (2H, t, J = 5.1 Hz), 3.38 (2H, t, J = 5.1 Hz), 3.84 (3H, s), 6.90 (3H, m), 7.12 (1H, dd, J = 9.0, 1.2 Hz), 7.20-7.30 (2H, m), 7.37 (1H, br), 7.51 (1H, d, J = 1.2 Hz), 7.77 (2H, d, J = 8.3 Hz)
13C-NMR (125 MHz, DMSO-d6): δ 38.89, 42.55, 55.60, 114.36, 117.71, 118.63, 122.22, 128.70, 130.38, 130.92, 131.83, 140.68, 154.80, 162.13
融点:150-151℃
1H-NMR (400 MHz, CDCl3): δ 3.12 (2H, t, J = 5.6 Hz), 3.40 (2H, t, J = 5.6 Hz), 7.00 (1H, br), 7.14 (1H, dd, J = 8.8, 2.6 Hz), 7.31 (1H, d, J = 8.8 Hz), 7.35 (1H, br), 7.42 (1H, br), 7.53 (1H, d, J = 2.6 Hz), 7.65 (2H, d, J = 8.7 Hz), 7.72 (2H, d, J = 8.7 Hz)
13C-NMR (100 MHz, DMSO-d6): δ 42.51, 54.90, 117.69, 118.66, 122.24, 126.21, 128.53, 130.41, 130.90, 132.29, 139.53, 140.62, 154.75
MS (EI): m/z 465 (M+)
融点:129-130℃
1H-NMR (400 MHz, CDCl3): δ 3.08 (2H, t, J = 5.1 Hz), 3.37 (2H, t, J = 5.1 Hz), 5.43 (1H, br), 5.73 (1H, br), 6.94 (1H, br), 7.10 (1H, dd, J = 8.4, 2.3 Hz), 7.21-7.27 (1H, m), 7.46 (2H, d, J = 8.5 Hz), 7.49 (1H, d, J = 2.3 Hz), 7.77 (2H, d, J = 8.5 Hz)
13C-NMR (125 MHz, Acetone-d6): δ 40.25, 44.30, 118.62, 120.07, 129.90, 129.53, 130.07, 131.14, 132.43, 138.77, 140.52, 141.51, 155.94
融点:139-140℃
1H-NMR (400 MHz, CDCl3): δ 3.11 (2H, t, J = 5.3 Hz), 3.19 (2H, t, J = 5.3 Hz), 6.67 (1H, br), 6.98 (1H, br), 7.13 (1H, dd, J = 8.6, 2.2 Hz), 7.18 (2H, t, J = 8.7 Hz), 7.30 (1H, d, J = 8.6 Hz), 7.40 (1H, br), 7.52 (1H, d, J = 2.2 Hz), 7.86 (2H, dd, J = 8.7, 5.0 Hz)
13C-NMR (125 MHz, DMSO-d6): δ 38.97, 42.55, 116.34 (d, J = 19.2 Hz), 117.71, 118.71, 122.29, 129.50 (d, J = 9.6 Hz), 130.38, 130.92, 136.60 (d, J = 3.6 Hz), 140.61, 154.80, 164.11 (d, J = 249.5 Hz)
融点:153-154℃
1H-NMR (400 MHz, CDCl3): δ 2.41 (3H, s), 3.12 (2H, t, J = 5.3 Hz), 3.41 (2H, t, J = 5.3 Hz), 6.79 (1H, br), 7.00 (1H, br), 7.23 (1H, br), 7.29 (2H, d, J = 8.1 Hz), 7.33 (1H, dd, J = 8.8, 2.3 Hz), 7.46 (1H, d, J = 2.3 Hz), 7.74 (2H, d, J = 8.1 Hz), 8.02 (1H, d, J = 8.8 Hz)
13C-NMR (125 MHz, DMSO-d6): δ 21.11, 38.89, 42.78, 112.75, 122.06, 126.71, 126.72, 129.77, 130.46, 131.14, 136.41, 137.48, 142.82, 154.72
融点:164-165℃
1H-NMR (500 MHz, CDCl3): δ 1.68 (2H, quint, J = 5.4 Hz), 2.40 (3H, s), 2.99 (2H, t, J = 5.4 Hz), 3.36 (2H, t, J = 5.4 Hz), 5.30 (1H, br), 5.42 (1H, br), 6.91 (1H, br), 7.15 (1H, dd, J = 8.7, 2.5 Hz), 7.24-7.28 (2H, m), 7.30 (1H, d, J = 8.7 Hz), 7.55 (1H, d, J = 2.5 Hz), 7.72 (2H, d, J = 8.6 Hz)
13C-NMR (125 MHz, DMSO-d6): δ 20.96, 29.73, 38.97, 40.34, 117.64, 118.71, 122.14, 126.49, 129.54, 130.31, 130.92, 137.48, 140.76, 142.59, 154.88
融点:157-158℃
1H-NMR (500 MHz, CDCl3): δ 1.70 (2H, quint, J = 6.0 Hz), 3.00 (2H, t, J = 6.0 Hz), 3.39 (2H, t, J = 6.0 Hz), 4.95 (1H, br), 5.55 (1H, br), 6.40 (1H, br), 7.13 (1H, dd, J = 9.0, 2.5 Hz), 7.35 (1H, d, J = 9.0 Hz), 7.54 (1H, d, J = 2.5 Hz), 7.60 (2H, d, J = 8.6 Hz), 7.71 (2H, d, J = 8.6 Hz)
13C-NMR (125 MHz, DMSO-d6): δ 29.73, 36.52, 40.34, 117.64, 118.71, 122.22, 126.18, 128.55, 130.38, 130.92, 132.29, 139.69, 140.76, 154.88
融点:163-164℃
1H-NMR (500 MHz, CDCl3): δ 1.70 (2H, quint, J = 6.0 Hz), 2.99 (2H, t, J = 6.0 Hz), 3.37 (2H, t, J = 6.0 Hz), 6.80 (1H, br), 6.92 (1H, br), 7.13 (1H, dd, J = 8.6, 2.9 Hz), 7.15 (2H, t, J = 8.5 Hz), 7.24-7.30 (1H, m), 7.33 (1H, d, J = 8.6 Hz), 7.53 (1H, d, J = 2.9 Hz), 7.85 (2H, dd, J = 8.5, 4.8 Hz)
13C-NMR (125 MHz, DMSO-d6): δ 29.73, 36.60, 40.34, 116.34 (d, J = 19.2 Hz), 117.71, 118.63, 122.14, 129.43 (d, J = 9.6 Hz), 130.38, 130.92, 136.79 (d, J = 2.8 Hz), 140.76, 154.88, 164.03 (d, J = 249.5 Hz)
融点:120-121℃
1H-NMR (500 MHz, CDCl3): δ 1.70 (2H, quint, J = 6.0 Hz), 2.98 (2H, t, J = 6.0 Hz), 3.38 (2H, t, J = 6.0 Hz), 3.84 (3H, s), 6.80 (1H, br), 6.90 (1H, br), 6.91 (2H, d, J = 8.6 Hz), 7.16 (1H, dd, J = 8.6, 2.3 Hz), 7.32 (1H, d, J = 8.6 Hz), 7.42 (1H, br), 7.56 (1H, d, J = 2.3 Hz), 7.76 (2H, d, J = 8.6 Hz)
13C-NMR (125 MHz, DMSO-d6): δ 29.21, 36.08, 39.74, 55.00, 113.76, 117.12, 118.11, 121.62, 128.10, 129.86, 130.39, 131.46, 140.24, 154.35, 161.53
融点:124-125℃
・N-[2-[3-(3-メトキシ-プロピル)チオウレイド)エチル]-4-メチル-ベンゼンスルホニルアミド
(ED-14)
1H-NMR (400 MHz, CDCl3): δ 1.85 (2H, quint, J = 5.2 Hz), 2.40 (3H, s), 3.15 (2H, t, J = 4.5 Hz), 3.33 (3H, s), 3.45-3.55 (4H, m), 3.69 (2H, t, J = 4.5 Hz), 7.29 (2H, d, J = 8.2 Hz), 7.72 (2H, d, J = 8.2 Hz)
13C-NMR (125 MHz, CDCl3): δ 21.45, 28.55, 42.66, 43.96, 53.73, 58.61, 70.59, 126.91, 129.73, 136.21, 143.54, 181.69
・4-メチル-N-[[2-(4-メチルフェニルスルホナミド)エチル]カルバモイル]ベンゼンスルホニルアミド
(ED-2)
1H-NMR (400 MHz, CDCl3): δ 2.43 (3H, s), 2.44 (3H, s), 3.04 (2H, t, J = 5.7 Hz), 3.33 (2H, t, J = 5.7 Hz), 5.08 (1H, br), 6.70 (1H, br), 7.30 (2H, d, J = 8.3 Hz), 7.35 (2H, d, J = 8.5 Hz), 7.71 (2H, d, J = 8.3 Hz), 7.82 (2H, d, J = 8.5 Hz), 7.94 (1H, br)
13C-NMR (125 MHz, DMSO-d6): δ 20.96, 21.02, 38.91, 42.08, 126.51, 127.21, 129.43, 129.67, 137.22, 137.35, 142.71, 143.61, 151.41
IR (KBr): 1155, 1327, 1522, 1692, 3328 cm-1
融点:163-164℃
1H-NMR (400 MHz, CDCl3): δ 2.41 (3H, s), 2.62 (3H, s), 3.00 (2H, t, J = 5.8 Hz), 3.31 (2H, t, J = 5.8 Hz), 5.30 (1H, br), 6.62 (1H, br), 7.28 (2H, d, J = 8.1 Hz), 7.32 (1H, d, J = 7.6 Hz), 7.36 (1H, t, J = 7.6 Hz), 7.51 (1H, t, J = 7.6 Hz), 7.69 (2H, d, J = 8.1 Hz), 8.01 (1H, d, J = 7.6 Hz), 8.60 (1H, br)
13C-NMR (125 MHz, CDCl3): δ 14.11, 21.51, 39.84, 42.81, 126.44, 127.01, 129.72, 129.83, 132.73, 133.67, 136.38, 137.38, 137.44, 143.64, 152.44
融点:134-135℃
・N-[2-[3-(3,4-ジクロロフェニル)ウレイド]フェニル]-4-メチル-ベンゼンスルホニルアミド
(ED-25)
1H-NMR (500 MHz, CDCl3): δ 2.40 (3H, s), 6.68 (1H, dd, J = 7.8, 1.2 Hz), 6.92 (1H, td, J = 7.8, 1.2 Hz), 7.06 (1H, br), 7.10 (1H, br), 7.18 (1H, dd, J = 9.0, 2.5 Hz), 7.20-7.27 (3H, m), 7.30 (1H, d, J = 9.0 Hz), 7.57 (1H, br), 7.58 (1H, d, J = 2.5 Hz), 7.64 (2H, d, J = 8.6 Hz), 7.79 (1H, dd, J = 7.8, 1.2 Hz)
13C-NMR (100 MHz, DMSO-d6): δ 21.00, 118.14, 119.16, 121.27, 122.41, 123.10, 125.35, 127.20, 127.32, 127.61, 129.52, 130.63, 131.11, 136.26, 136.46, 140.08, 143.30, 152.18
融点:204-205℃
1H-NMR (500 MHz, CDCl3): δ 2.41 (3H, s), 6.38 (1H, br), 6.80 (1H, br), 6.92-7.16 (3H, m), 7.19 (1H, td, J = 7.8, 1.3 Hz), 7.23-7.35 (4H, m), 7.48 (1H, td, J = 7.8, 1.3 Hz), 7.76 (2H, d, J = 8.0 Hz), 7.87 (1H, dd, J = 7.8, 1.3 Hz), 8.30 (1H, br)
13C-NMR (125 MHz, DMSO-d6): δ 20.96, 115.04, 115.27 (d, J = 19.2 Hz), 121.00, 121.99, 123.36, 125.12, 127.21 (d, J = 9.6 Hz), 127.56, 129.54, 136.03, 136.41, 136.91 (d, J = 3.0 Hz), 143.28, 152.74, 157.36 (d, J = 239.9 Hz)
融点:180-181℃
1H-NMR (400 MHz, CDCl3): δ 6.69 (1H, dd, J = 8.1, 1.5 Hz), 6.96 (1H, td, J = 8.1, 1.5 Hz), 7.06 (1H, br), 7.10 (1H, br), 7.20 (1H, dd, J = 8.7, 2.4 Hz), 7.21-7.25 (1H, m), 7.32 (1H, d, J = 8.7 Hz), 7.42 (1H, br), 7.55-7.58 (4H, m), 7.59 (1H, d, J = 2.4 Hz), 7.72 (1H, dd, J = 8.1, 1.5 Hz)
13C-NMR (125 MHz, DMSO-d6): δ 118.17, 119.21, 121.48, 122.61, 123.15, 124.98, 126.93, 127.47, 127.89, 129.14, 130.61, 131.12, 132.20, 136.49, 138.36, 139.98, 152.13
融点:211-212 ℃
1H-NMR (400 MHz, CDCl3): δ 6.68 (1H, dd, J = 7.6, 1.5 Hz), 6.94 (1H, td, J = 7.6, 1.5 Hz), 7.15 (1H, dd, J = 8.8, 2.4 Hz), 7.20 (1H, td, J = 7.6, 1.5 Hz), 7.22-7.27 (2H, m), 7.29 (1H, d, J = 8.8 Hz), 7.41 (2H, d, J = 8.8 Hz), 7.48 (1H, br), 7.55 (1H, d, J = 2.4 Hz), 7.65-7.69 (3H, m)
13C-NMR (125 MHz, DMSO-d6): δ 118.17, 119.21, 121.48, 122.60, 123.15, 125.00, 127.48, 127.89, 129.07, 129.27, 130.60, 131.12, 136.50, 137.93, 139.98, 140.06, 152.15
融点:199-200℃
1H-NMR (400 MHz, CDCl3): δ 6.61 (1H, dd, J = 8.1, 1.5 Hz), 6.92 (1H, td, J = 8.1, 1.5 Hz), 7.00 (1H, br), 7.13 (2H, t, J = 8.5 Hz), 7.18-7.25 (3H, m), 7.31 (1H, d, J = 8.5 Hz), 7.52 (1H, br), 7.60 (1H, d, J = 2.4 Hz), 7.74 (2H, dd, J = 8.5, 7.0 Hz), 7.78 (1H, dd, J = 8.1, 1.5 Hz)
13C-NMR (125 MHz, DMSO-d6): δ 116.31 (d, J = 22.8 Hz), 118.16, 119.20, 121.35, 122.51, 123.16, 125.08, 127.46, 127.85, 130.25 (d, J = 9.6 Hz), 130.62, 131.12, 135.36, 136.57, 140.01, 152.18, 164.43 (d, J = 251.9 Hz)
融点:203-204℃
1H-NMR (400 MHz, CDCl3): δ 2.34 (3H, s), 6.70 (1H, br), 6.83 (1H, dd, J = 8.1, 1.5 Hz), 6.95 (1H, td, J = 8.1, 1.5 Hz), 7.12-7.22 (5H, m), 7.25-7.34 (5H, m), 7.58 (2H, d, J = 8.3 Hz), 7.66 (1H, dd, J = 8.1, 1.5 Hz)
13C-NMR (125 MHz, DMSO-d6): δ 20.99, 115.89, 117.90, 118.15, 120.94, 121.84, 121.91, 125.07, 127.18, 128.81, 129.51, 136.43, 139.82, 140.87, 143.27, 152.46
融点:83-84℃
1H-NMR (400 MHz, CDCl3): δ 3.80 (3H, s), 6.66 (1H, dd, J = 8.1, 1.5 Hz), 6.86 (2H, d, J = 8.9 Hz), 6.88 (1H, td, J = 8.1, 1.5 Hz), 7.13 (1H, dd, J = 8.5, 2.4 Hz), 7.18 (1H, td, J = 8.1, 1.5 Hz), 7.23-7.25 (2H, m), 7.29 (1H, br), 7.54 (1H, d, J = 2.4 Hz), 7.61 (1H, br), 7.66 (2H, d, J = 8.9 Hz), 7.76 (1H, dd, J = 8.1, 1.5 Hz)
13C-NMR (125 MHz, DMSO-d6): δ 55.57, 114.18, 118.15, 119.16, 121.14, 122.38, 123.09, 125.48, 127.38, 127.54, 129.37, 130.62, 130.64, 131.09, 136.46, 140.06, 152.18, 162.51
融点:129-130℃
1H-NMR (400 MHz, CDCl3): δ 2.33 (3H, s), 3.77 (3 H, s) 6.63 (1H, dd, J = 8.1, 1.5 Hz), 6.77-6.82 (3H, m), 6.84 (1H, dd, J = 8.2, 1.9 Hz), 6.94 (1H, td, J = 8.1, 1.5 Hz), 7.02 (1H, t, J = 1.9 Hz), 7.11-7.20 (4H, m), 7.33 (1H, br), 7.58 (2H, d, J = 8.5 Hz), 7.72 (1H, dd, J = 8.1, 1.5 Hz)
13C-NMR (125 MHz, DMSO-d6): δ 21.00, 54.88, 103.87, 107.32, 110.46, 115.89, 116.80, 121.94, 125.10, 127.20, 127.55, 129.51, 129.58, 136.43, 136.92, 141.08, 143.28, 152.40, 159.70
融点:84-85℃
1H-NMR (400 MHz, CDCl3): δ 2.29 (3H, s), 3.83 (3H, s), 6.86 (1H, dd, J = 8.1, 1.5 Hz), 6.93-7.00 (5H, m), 7.13-7.23 (5H, m), 7.56 (1H, dd, J = 8.1, 1.5 Hz), 7.57 (2H, d, J = 8.3 Hz), 7.99 (1H, dd, J = 8.1, 1.7 Hz)
13C-NMR (125 MHz, DMSO-d6): δ 20.96, 55.73, 110.81, 119.21, 120.46, 121.84, 122.11, 122.39, 126.13, 126.64, 126.95, 127.03, 128.53, 129.47, 135.86, 136.85, 143.13, 148.18, 152.77
融点:105-106℃
1H-NMR (400 MHz, CDCl3): δ 6.90 (1H, br), 7.01 (1H, dd, J = 8.1, 1.5 Hz), 7.08 (1H, td, J = 8.1, 1.5 Hz), 7.19 (1H, br), 7.20-7.26 (3H, m), 7.35 (1H, d, J = 2.4 Hz), 7.51 (2H, d, J = 8.8 Hz), 7.55 (2H, d, J = 8.8 Hz), 7.57 (1H, dd, J = 8.1, 1.5 Hz), 8.06 (1H, d, J = 9.0 Hz)
13C-NMR (125 MHz, DMSO-d6): δ 122.14, 122.92, 123.28, 123.40, 125.78, 126.45, 126.81, 127.19, 127.52, 127.60, 128.62, 129.01, 132.17, 135.20, 135.98, 138.74, 152.34
融点:209-210℃
1H-NMR (400 MHz, CDCl3): δ 6.92 (1H, dd, J = 8.1, 1.5 Hz), 6.93 (1H, br), 7.02-7.08 (3H, m), 7.14 (1H, br), 7.21-7.25 (2H, m), 7.32 (1H, br), 7.34 (1H, d, J = 2.2 Hz), 7.63 (1H, dd, J = 8.1, 1.5 Hz), 7.72 (2H, dd, J = 8.8, 4.9 Hz), 8.07 (1H, d, J = 9.0 Hz)
13C-NMR (125 MHz, DMSO-d6): δ 116.27 (d, J = 22.8 Hz), 122.07, 122.85, 123.31, 123.46, 125.91, 126.51, 127.21, 127.52, 127.56, 128.64, 130.12 (d, J = 9.6 Hz), 135.23, 135.77 (d, J = 2.4 Hz), 136.07, 152.42, 164.39 (d, J = 250.7 Hz)
融点:201-202℃
1H-NMR (400 MHz, CDCl3): δ 6.94 (1H, br), 6.99 (1H, dd, J = 8.1, 1.5 Hz), 7.07 (1H, td, J = 8.1, 1.5 Hz), 7.20-7.30 (4H, m), 7.34 (1H, d, J = 2.4 Hz), 7.35 (2H, d, J = 8.8 Hz), 7.58 (1H, dd, J = 8.1, 1.5 Hz), 7.63 (2H, d, J = 8.8 Hz), 8.06 (1H, d, J = 9.0 Hz)
13C-NMR (125 MHz, DMSO-d6): δ 122.17, 122.92, 123.27, 123.41, 125.83, 126.47, 127.21, 127.50, 127.58, 128.60, 128.93, 129.22, 135.20, 135.96, 137.82, 138.33, 152.36
融点:201-202℃
1H-NMR (400 MHz, CDCl3): δ 2.34 (3H, s), 3.49 (1H, br), 6.79 (1H, d, J = 15.9 Hz), 7.03 (1H, td, J = 8.1, 1.5 Hz), 7.10-7.30 (8H, m), 7.36 (1H, d, J = 15.9 Hz), 7.43 (1H, br), 7.53 (1H, d, J = 2.4 Hz), 7.60 (1H, br), 7.72 (1H, dd, J = 8.1, 1.5 Hz)
13C-NMR (125 MHz, DMSO-d6): δ 20.98, 118.13, 119.18, 121.42, 122.76, 123.08, 124.75, 125.57, 127.67, 128.43, 128.88, 129.45, 129.65, 130.51, 131.02, 136.29, 139.98, 140.64, 140.99, 152.20
融点:182-183℃
Claims (17)
- 下記一般式[MM_1]、[DR_1]、[DR’_1]、[LW_1]および[ED_1]のいずれかの化合物群から選ばれる1つ以上の化合物を有効成分とするセリンラセマーゼ阻害剤。
で表されるフェノキシ-(N-置換カルバモイルメチル)-アセトアミド誘導体。
で表されるN-(置換)-2-(置換スルファモイルアミノ)-アセトアミド誘導体。
で表されるN-(置換)-2-(置換スルファモイルアミノ)-アセトアミド誘導体。
で表されるN-[(アシル)ヒドラジノカルボチオニル]-アセトアミド誘導体
で表されるベンゼンスルホニルアミド誘導体。 - 下記一般式[LW_1g]
(1)R24wが、ハロゲン原子;R22w、R23w、R25wおよびR26wは、水素原子
(2)R23wが、アルキル基;R22w、R24w、R25wおよびR26wは、水素原子
(3)R22wおよびR26wが、ハロゲン原子;R23w、R24wおよびR26wは、水素原子
(4)R23wおよびR25wが、ハロゲン原子;R22w、R24wおよびR26wは、水素原子」
で表されるN-[(アシル)ヒドラジノカルボチオニル]-アセトアミド誘導体。
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US14/375,006 US9216954B2 (en) | 2012-01-27 | 2013-01-24 | Serine racemase inhibitor |
JP2013555295A JP6037396B2 (ja) | 2012-01-27 | 2013-01-24 | セリンラセマーゼ阻害剤 |
CA2863006A CA2863006A1 (en) | 2012-01-27 | 2013-01-24 | Serine racemase inhibitor |
KR1020147023788A KR20150000875A (ko) | 2012-01-27 | 2013-01-24 | 세린 라세마제 저해제 |
CN201380017021.8A CN104220058A (zh) | 2012-01-27 | 2013-01-24 | 丝氨酸消旋酶抑制剂 |
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JP2012049955 | 2012-03-07 | ||
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EP (1) | EP2808014A4 (ja) |
JP (1) | JP6037396B2 (ja) |
KR (1) | KR20150000875A (ja) |
CN (1) | CN104220058A (ja) |
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Cited By (4)
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WO2014080615A1 (ja) * | 2012-11-21 | 2014-05-30 | 日本曹達株式会社 | 非フェノール系化合物を用いた記録材料 |
JP5887423B2 (ja) * | 2012-11-21 | 2016-03-16 | 日本曹達株式会社 | 非フェノール系化合物を用いた記録材料 |
US9518011B2 (en) | 2012-11-21 | 2016-12-13 | Nippon Soda Co., Ltd. | Recording material produced using non-phenol compound |
JPWO2014080615A1 (ja) * | 2012-11-21 | 2017-01-05 | 日本曹達株式会社 | 非フェノール系化合物を用いた記録材料 |
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CN104220058A (zh) | 2014-12-17 |
TW201339126A (zh) | 2013-10-01 |
JPWO2013111798A1 (ja) | 2015-05-11 |
JP6037396B2 (ja) | 2016-12-07 |
CA2863006A1 (en) | 2013-08-01 |
EP2808014A1 (en) | 2014-12-03 |
EP2808014A4 (en) | 2016-01-13 |
KR20150000875A (ko) | 2015-01-05 |
US9216954B2 (en) | 2015-12-22 |
US20140371291A1 (en) | 2014-12-18 |
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