RU2012114846A - Соединение глицина - Google Patents
Соединение глицина Download PDFInfo
- Publication number
- RU2012114846A RU2012114846A RU2012114846/04A RU2012114846A RU2012114846A RU 2012114846 A RU2012114846 A RU 2012114846A RU 2012114846/04 A RU2012114846/04 A RU 2012114846/04A RU 2012114846 A RU2012114846 A RU 2012114846A RU 2012114846 A RU2012114846 A RU 2012114846A
- Authority
- RU
- Russia
- Prior art keywords
- substituted
- lower alkyl
- compound
- pyrimidin
- represent
- Prior art date
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- -1 Glycine Compound Chemical class 0.000 title claims abstract 51
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 title claims 2
- 239000004471 Glycine Substances 0.000 title claims 2
- 125000000217 alkyl group Chemical group 0.000 claims abstract 34
- 150000001875 compounds Chemical class 0.000 claims abstract 26
- 150000003839 salts Chemical class 0.000 claims abstract 26
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract 14
- 229910052736 halogen Inorganic materials 0.000 claims abstract 11
- 150000002367 halogens Chemical class 0.000 claims abstract 10
- 125000003118 aryl group Chemical group 0.000 claims abstract 6
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract 4
- 125000003342 alkenyl group Chemical group 0.000 claims abstract 3
- 125000005843 halogen group Chemical group 0.000 claims abstract 3
- 101710132836 Membrane primary amine oxidase Proteins 0.000 claims 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims 5
- 201000010099 disease Diseases 0.000 claims 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 5
- 102000056133 human AOC3 Human genes 0.000 claims 5
- 238000011282 treatment Methods 0.000 claims 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 4
- BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical compound NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 claims 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 3
- 239000008194 pharmaceutical composition Substances 0.000 claims 3
- 230000002265 prevention Effects 0.000 claims 3
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims 3
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims 2
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 2
- 238000011321 prophylaxis Methods 0.000 claims 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 2
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims 2
- NSGJXPYAUQEKJI-VOTSOKGWSA-N (e)-3-[6-[4-[5-[3-[[(2-aminoacetyl)-methylamino]methyl]phenyl]pyrimidin-2-yl]piperazin-1-yl]-5-methylpyridin-3-yl]prop-2-enoic acid Chemical compound NCC(=O)N(C)CC1=CC=CC(C=2C=NC(=NC=2)N2CCN(CC2)C=2C(=CC(\C=C\C(O)=O)=CN=2)C)=C1 NSGJXPYAUQEKJI-VOTSOKGWSA-N 0.000 claims 1
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 claims 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims 1
- FREZDGCRHGKROQ-UHFFFAOYSA-N 2-amino-n-[[3-[2-(1,1-dioxo-1,4-thiazinan-4-yl)pyrimidin-5-yl]phenyl]methyl]-n-methylacetamide Chemical compound NCC(=O)N(C)CC1=CC=CC(C=2C=NC(=NC=2)N2CCS(=O)(=O)CC2)=C1 FREZDGCRHGKROQ-UHFFFAOYSA-N 0.000 claims 1
- VBOFEELDRIJUQG-UHFFFAOYSA-N 2-amino-n-[[3-[2-(4-hydroxypiperidin-1-yl)pyrimidin-5-yl]phenyl]methyl]-n-methylacetamide Chemical compound NCC(=O)N(C)CC1=CC=CC(C=2C=NC(=NC=2)N2CCC(O)CC2)=C1 VBOFEELDRIJUQG-UHFFFAOYSA-N 0.000 claims 1
- PFHNADXHZMQLMB-UHFFFAOYSA-N 2-amino-n-[[3-[2-(5,7-dihydropyrrolo[3,4-b]pyridin-6-yl)pyrimidin-5-yl]phenyl]methyl]-n-methylacetamide Chemical compound NCC(=O)N(C)CC1=CC=CC(C=2C=NC(=NC=2)N2CC3=NC=CC=C3C2)=C1 PFHNADXHZMQLMB-UHFFFAOYSA-N 0.000 claims 1
- DXHATKDTFCBJTO-GASCZTMLSA-N 2-amino-n-[[3-[2-[(2r,6s)-2,6-dimethylmorpholin-4-yl]pyrimidin-5-yl]phenyl]methyl]-n-methylacetamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C1=NC=C(C=2C=C(CN(C)C(=O)CN)C=CC=2)C=N1 DXHATKDTFCBJTO-GASCZTMLSA-N 0.000 claims 1
- RYSDLCBJBNSEBB-INIZCTEOSA-N 2-amino-n-[[3-[2-[(3s)-3-fluoropyrrolidin-1-yl]pyrimidin-5-yl]phenyl]methyl]-n-methylacetamide Chemical compound NCC(=O)N(C)CC1=CC=CC(C=2C=NC(=NC=2)N2C[C@@H](F)CC2)=C1 RYSDLCBJBNSEBB-INIZCTEOSA-N 0.000 claims 1
- UYJLLJSCJALZRB-UHFFFAOYSA-N 2-amino-n-[[3-[2-[2-(hydroxymethyl)morpholin-4-yl]pyrimidin-5-yl]phenyl]methyl]-n-methylacetamide Chemical compound NCC(=O)N(C)CC1=CC=CC(C=2C=NC(=NC=2)N2CC(CO)OCC2)=C1 UYJLLJSCJALZRB-UHFFFAOYSA-N 0.000 claims 1
- BBDPFGPPTUKKBZ-UHFFFAOYSA-N 2-amino-n-[[3-[2-[4-(3-chloropyridin-2-yl)piperazin-1-yl]pyrimidin-5-yl]phenyl]methyl]-n-methylacetamide Chemical compound NCC(=O)N(C)CC1=CC=CC(C=2C=NC(=NC=2)N2CCN(CC2)C=2C(=CC=CN=2)Cl)=C1 BBDPFGPPTUKKBZ-UHFFFAOYSA-N 0.000 claims 1
- MTDXPHYPJFKQMN-UHFFFAOYSA-N 2-amino-n-[[3-[2-[4-(6-cyanopyridin-3-yl)piperidin-1-yl]pyrimidin-5-yl]phenyl]methyl]-n-methylacetamide Chemical compound NCC(=O)N(C)CC1=CC=CC(C=2C=NC(=NC=2)N2CCC(CC2)C=2C=NC(=CC=2)C#N)=C1 MTDXPHYPJFKQMN-UHFFFAOYSA-N 0.000 claims 1
- LXVCULZUKZONSR-IYBDPMFKSA-N 2-amino-n-[[3-[6-[(2s,6r)-2,6-dimethylmorpholin-4-yl]pyridin-3-yl]phenyl]methyl]-n-methylacetamide Chemical compound C1[C@@H](C)O[C@@H](C)CN1C1=CC=C(C=2C=C(CN(C)C(=O)CN)C=CC=2)C=N1 LXVCULZUKZONSR-IYBDPMFKSA-N 0.000 claims 1
- HKPHKNCGPOEEFL-UHFFFAOYSA-N 2-amino-n-methyl-n-[[3-[2-(4-pyridin-3-yl-3,6-dihydro-2h-pyridin-1-yl)pyrimidin-5-yl]phenyl]methyl]acetamide Chemical compound NCC(=O)N(C)CC1=CC=CC(C=2C=NC(=NC=2)N2CC=C(CC2)C=2C=NC=CC=2)=C1 HKPHKNCGPOEEFL-UHFFFAOYSA-N 0.000 claims 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims 1
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- QDGSBIRQNOGSOH-UHFFFAOYSA-N 3-[6-[4-[5-[3-[[(2-aminoacetyl)-methylamino]methyl]phenyl]pyrimidin-2-yl]piperazin-1-yl]-5-methylpyridin-3-yl]propanoic acid Chemical compound NCC(=O)N(C)CC1=CC=CC(C=2C=NC(=NC=2)N2CCN(CC2)C=2C(=CC(CCC(O)=O)=CN=2)C)=C1 QDGSBIRQNOGSOH-UHFFFAOYSA-N 0.000 claims 1
- WUPBTBRKQPXTEW-UHFFFAOYSA-N 4-[4-[5-[3-[[(2-aminoacetyl)-methylamino]methyl]phenyl]pyrimidin-2-yl]piperazin-1-yl]-3-chlorobenzoic acid Chemical compound NCC(=O)N(C)CC1=CC=CC(C=2C=NC(=NC=2)N2CCN(CC2)C=2C(=CC(=CC=2)C(O)=O)Cl)=C1 WUPBTBRKQPXTEW-UHFFFAOYSA-N 0.000 claims 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 125000004093 cyano group Chemical group *C#N 0.000 claims 1
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 1
- 229960003512 nicotinic acid Drugs 0.000 claims 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N nicotinic acid Natural products OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims 1
- 235000001968 nicotinic acid Nutrition 0.000 claims 1
- 239000011664 nicotinic acid Substances 0.000 claims 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 239000010802 sludge Substances 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 abstract 1
Classifications
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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
- C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
- C07C237/40—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
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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
- C07C237/04—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 the carbon skeleton being acyclic and saturated
- C07C237/06—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 the carbon skeleton being acyclic and saturated having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
- 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
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- C07C237/04—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 the carbon skeleton being acyclic and saturated
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Abstract
1. Соединение, представленное формулой (I), или его соль:[Хим. 1](гдеRпредставляет собой H или низший алкил, который может быть замещен,Rпредставляет собой галоген,Rи Rявляются одинаковыми или отличаются друг от друга и представляют собой H или галоген,m равен 0, 1, 2, 3 или 4,Yи Yявляются одинаковыми или отличаются друг от друга и представляют собой N или CR,Rпредставляет собой H или галоген,X представляет собой H, галоген, Z-(CRR)-, RRN-SO- или низший алкенил, который может быть замещен,n равен 0 или 1,Rи Rявляются одинаковыми или отличаются друг от друга и представляют собой H, или Rи Rобъединены вместе с образованием оксо (=O),Rи Rявляются одинаковыми или отличаются друг от друга и представляют собой H или низший алкил,Z представляет собой RRN-, RO- или[Хим. 2]Rи Rявляются одинаковыми или отличаются друг от друга и представляют собой H, -C(=O)-R, -C(=O)-O-R, -C(=O)-NH, -C(=O)-NHR, -C(=O)-N(R), -SO-(низший алкил, который может быть замещен), -SO-(арил, который может быть замещен), низший алкил, который может быть замещен, или гетероциклическую группу, которая может быть замещена,Rявляются одинаковыми или отличаются друг от друга и представляют собой низший алкил, который может быть замещен, циклоалкил, который может быть замещен, или гетероциклическую группу, которая может быть замещена,Rпредставляет собой низший алкил, который может быть замещен, или гетероциклическую группу, которая может быть замещена,p равен 0, 1 или 2,q равен 1 или 2,E представляет собой CH или N,G представляет собой CRR, NR, O или SO,Rи Rявляются одинаковыми или отличаются друг от друга и представляют собой H, OH, NH, -C(=O)-R, -C(=O)-O-R, -C(=O)-NHR, -C(=O)-N(R), -SO-R, амино, который может быть замещен, или низший алкил, который может быть замещен, цикл
Claims (25)
1. Соединение, представленное формулой (I), или его соль:
[Хим. 1]
(где
R1 представляет собой H или низший алкил, который может быть замещен,
R2 представляет собой галоген,
R3 и R4 являются одинаковыми или отличаются друг от друга и представляют собой H или галоген,
m равен 0, 1, 2, 3 или 4,
Y1 и Y2 являются одинаковыми или отличаются друг от друга и представляют собой N или CRY,
RY представляет собой H или галоген,
X представляет собой H, галоген, Z-(CR11R12)n-, R13R14N-SO2- или низший алкенил, который может быть замещен,
n равен 0 или 1,
R11 и R12 являются одинаковыми или отличаются друг от друга и представляют собой H, или R11 и R12 объединены вместе с образованием оксо (=O),
R13 и R14 являются одинаковыми или отличаются друг от друга и представляют собой H или низший алкил,
Z представляет собой RZ1RZ2N-, RZ3O- или
[Хим. 2]
RZ1 и RZ2 являются одинаковыми или отличаются друг от друга и представляют собой H, -C(=O)-RZ11, -C(=O)-O-RZ11, -C(=O)-NH2, -C(=O)-NHRZ11, -C(=O)-N(RZ11)2, -SO2-(низший алкил, который может быть замещен), -SO2-(арил, который может быть замещен), низший алкил, который может быть замещен, или гетероциклическую группу, которая может быть замещена,
RZ11 являются одинаковыми или отличаются друг от друга и представляют собой низший алкил, который может быть замещен, циклоалкил, который может быть замещен, или гетероциклическую группу, которая может быть замещена,
RZ3 представляет собой низший алкил, который может быть замещен, или гетероциклическую группу, которая может быть замещена,
p равен 0, 1 или 2,
q равен 1 или 2,
E представляет собой CH или N,
G представляет собой CRG1RG2, NRG3, O или SO2,
RG1 и RG2 являются одинаковыми или отличаются друг от друга и представляют собой H, OH, NH2, -C(=O)-RG31, -C(=O)-O-RG31, -C(=O)-NHRG31, -C(=O)-N(RG31)2, -SO2-RG31, амино, который может быть замещен, или низший алкил, который может быть замещен, циклоалкил, который может быть замещен, арил, который может быть замещен, или гетероциклическую группу, которая может быть замещена,
RG3 представляет собой H, NH2, -C(=O)-RG31, -C(=O)-O-RG31, -C(=O)-NHRG31, -C(=O)-N(RG31)2, -SO2-RG31 или низший алкил, который может быть замещен, циклоалкил, который может быть замещен, арил, который может быть замещен, или гетероциклическую группу, которая может быть замещена,
RG31 являются одинаковыми или отличаются друг от друга и представляют собой низший алкил, который может быть замещен, циклоалкил, который может быть замещен, арил, который может быть замещен, или гетероциклическую группу, которая может быть замещена, и
R21, R22, R23, R24, R25 и R26 являются одинаковыми или отличаются друг от друга и представляют собой H, OH, галоген, NH2, амино, который может быть замещен, или низший алкил, который может быть замещен,
в котором RG1 или RG2 могут быть объединены либо с R21, либо с R22 с образованием новой связи, или
RG1, RG2, R21 и R22 могут быть объединены вместе с образованием азотсодержащей гетероциклической группы, которая может быть замещена, и
RG3, R21 и R22 могут быть объединены вместе с образованием азотсодержащей гетероциклической группы, которая может быть замещена).
2. Соединение или его соль по п.1, где Y1 и Y2 оба представляют собой CRY, и оба RY представляют собой H.
3. Соединение или его соль по п.1, где Y1 и Y2 оба представляют собой N.
4. Соединение или его соль по п.1, где Y1 представляет собой N, Y2 представляет собой CRY, и RY представляет собой H.
6. Соединение или его соль по п.5, где E представляет собой N, G представляет собой CRG1RG2, O или SO2, p равен 1, и q равен 1 или 2.
8. Соединение или его соль по п.7, где G представляет собой O или SO2, и R21, R22, R23, R24, R25 и R26 являются одинаковыми или отличаются друг от друга и представляют собой H, метил или гидроксиметил.
10. Соединение или его соль по п.9, где RG1 и RG2 являются одинаковыми или отличаются друг от друга и представляют собой H, OH или гетероциклическую группу, которая может быть замещена,
R21, R22, R23, R24, R25 и R26 представляют собой H, или
RG1, RG2, R21 и R22 могут быть объединены вместе с образованием азотсодержащей гетероциклической группы, которая может быть замещена, и
RG1 или RG2 могут быть объединены либо с R21, либо с R22 с образованием новой связи.
11. Соединение или его соль по п.9, где RG1 и RG2 являются одинаковыми или отличаются друг от друга и представляют собой H, OH или пиридин или морфолин, которые могут быть замещены,
R21, R22, R23, R24, R25 и R26 представляют собой H или F, или
RG1, RG2, R21 и R22 могут быть объединены вместе с образованием пиридина или тиазола, которые могут быть замещены, и
RG1 или RG2 могут быть объединены либо с R21, либо с R22 с образованием новой связи.
12. Соединение или его соль по п.9, где RG1 и RG2 являются одинаковыми или отличаются друг от друга и представляют собой H, OH или пиридин-3-ил или морфолин-4-ил, или RG1, RG2, R21 и R22 объединены с атомами углерода, к которым они присоединены, с образованием
[Хим. 6]
или
R21, R22, R23, R24, R25 и R26 представляют собой H или F.
13. Соединение или его соль по п.5, где E представляет собой N, G представляет собой NRG3, p равен 1, и q равен 2.
14. Соединение или его соль по п.5, где Z представляет собой
[Хим. 7]
R21, R22, R23, R24, R25 и R26 представляют собой H, Y4 представляет собой N или CRY41, Y5 представляет собой N или CRY51, RY41, RY51 и RG32 представляют собой H, галоген, -OH, -O-низший алкил (в котором низший алкил может быть замещен 1-3 заместителями, представляющими собой OH, галоген, -O-низший алкил (в котором низший алкил может быть замещен одной или несколькими -COOH группами), или арильные группы), -CHO, -CO-низший алкил (в котором низший алкил может быть замещен 1-3 атомами галогена), -CO-циклоалкил (в котором циклоалкил может быть замещен одной или несколькими -O-низшими алкильными группами), -CO-арил, -CO-моноциклическая насыщенная гетероциклическая кольцевая группа, циано, -COOH, -COO-низший алкил (в котором низший алкил может быть замещен 1-3 атомами галогена), -NH2, NH(низший алкил), N(низший алкил)2 или низший алкил, который может быть замещен -COOH или -O-низшим алкилом (в котором низший алкил может быть замещен одной или несколькими -COOH группами), или низший алкенил, который может быть замещен -COOH или -O-низшим алкилом (в котором низший алкил может быть замещен одной или несколькими -COOH группами), и s равен 0, 1, 2 или 3.
15. Соединение или его соль по п.5, где Z представляет собой
[Хим. 8]
R21, R22, R23, R24, R25 и R26 представляют собой H, и
[Хим. 9]
представляет собой фенил, 4-аминофенил, 4-диметиламинофенил, 4-карбоксифенил, 4-карбокси-6-хлор-фенил, 4-метилфенил, 4-фторфенил, 4-хлорфенил, 2-фторфенил, 2-метилфенил, 2,4-дифторфенил, 2-метоксифенил, 3-метилпиридин-2-ил, 3-трифторметилпиридин-2-ил, 3-циано-6-метилпиридин-2-ил, 5-[(E)-2-карбоксивинил]-3-метилпиридин-2-ил, 5-карбокси-3-хлорпиридин-2-ил, 5-[(E)-2-карбоксивинил]-3-хлорпиридин-2-ил, 3-карбоксиметоксиметилпиридин-2-ил, 5-(2-карбоксиэтил)-3-метилпиридин-2-ил, 5-карбоксипиридин-2-ил, пиридин-2-ил, 5-этоксикарбонилпиридин-2-ил, 5-цианопиридин-2-ил, 3-цианопиридин-2-ил, 3-хлорпиридин-2-ил, 5-трифторметилпиридин-2-ил, 3-фторпиридин-2-ил, 5-фторпиридин-2-ил, 5-хлорпиридин-2-ил, 5-бромпиридин-2-ил, 3-метоксипиридин-2-ил, 3-гидроксиметилпиридин-2-ил, 5-метилпиридин-2-ил, 4-метилпиридин-2-ил, 5-карбокси-3-метилпиридин-2-ил, 6-метилпиридин-2-ил, 5-(2-карбоксиэтил)-3-гидроксиметилпиридин-2-ил, 5-[(E)-2-карбоксивинил]-3-гидроксиметилпиридин-2-ил, 5-[(E)-2-карбоксивинил]пиридин-2-ил, 5-(2-карбоксиэтил)пиридин-2-ил, 6-хлорпиридин-3-ил, 4-метилпиридин-3-ил, 5-этоксикарбонилпиридин-3-ил, 5-метилпиридин-3-ил, 2-метилпиридин-3-ил, пиридин-3-ил, 6-аминопиридин-3-ил, 5-хлорпиридин-3-ил, 5-карбоксипиридин-3-ил или 6-цианопиридин-3-ил, 6-хлорпиримидин-3-ил или пиримидин-3-ил.
16. Соединение или его соль по п.5, где R1 представляет собой низший алкил, который может быть замещен.
17. Соединение или его соль по п.1, где R3 и R4 представляют собой H.
18. Соединение или его соль по п.1, где m равен 0.
19. Соединение или его соль по п.1, которое представляет собой:
N-метил-N-[3-(2-морфолин-4-илпиримидин-5-ил)бензил]глицинамид,
N-метил-N-[3-(2-пирролидин-1-илпиримидин-5-ил)бензил]глицинамид,
N-(3-{2-[(2R,6S)-2,6-диметилморфолин-4-ил]пиримидин-5-ил}бензил)-N-метилглицинамид,
N-(3-{2-[2-(гидроксиметил)морфолин-4-ил]пиримидин-5-ил}бензил)-N-метилглицинамид,
N-(3-{6-[(2R,6S)-2,6-диметилморфолин-4-ил]пиридин-3-ил}бензил)-N-метилглицинамид,
N-{3-[2-(4-гидроксипиперидин-1-ил)пиримидин-5-ил]бензил}-N-метилглицинамид,
N-{3-[2-(1,1-диоксидотиоморфолин-4-ил)пиримидин-5-ил]бензил}-N-метилглицинамид,
N-метил-N-{3-[2-(4-морфолин-4-илпиперидин-1-ил)пиримидин-5-ил]бензил}глицинамид,
N-{3-[2-(3',6'-дигидро-3,4'-бипиридин-1'(2'H)-ил)пиримидин-5-ил]бензил}-N-метилглицинамид,
N-метил-N-{3-[2-(4-пиридин-3-илпиперидин-1-ил)пиримидин-5-ил]бензил}глицинамид,
N-метил-N-(3-{2-[4-(3-метилпиридин-2-ил)пиперазин-1-ил]пиримидин-5-ил}бензил)глицинамид,
(2E)-3-(6-{4-[5-(3-{[глицил(метил)амино]метил}фенил)пиримидин-2-ил]пиперазин-1-ил}-5-метилпиридин-3-ил)акриловую кислоту,
3-(6-{4-[5-(3-{[глицил(метил)амино]метил}фенил)пиримидин-2-ил]пиперазин-1-ил}-5-метилпиридин-3-ил)пропионовую кислоту,
5-хлор-6-{4-[5-(3-{глицил(метил)амино]метил}фенил)пиримидин-2-ил]пиперазин-1-ил}никотиновую кислоту,
(2E)-3-(5-хлор-6-{4-[5-(3-{[глицил(метил)амино]метил}фенил)пиримидин-2-ил]пиперазин-1-ил}пиридин-3-ил)акриловую кислоту,
3-хлор-4-{4-[5-(3-{[глицил(метил)амино]метил}фенил)пиримидин-2-ил]пиперазин-1-ил}бензойную кислоту,
N-(3-{2-[4-(6-цианопиридин-3-ил)пиперидин-1-ил]пиримидин-5-ил}бензил)-N-метилглицинамид,
N-метил-N-(3-{2-[4-(2-метилпиридин-3-ил)пиперидин-1-ил]пиримидин-5-ил}бензил)глицинамид,
N-(3-{2-[4-(3-хлорпиридин-2-ил)пиперазин-1-ил]пиримидин-5-ил}бензил)-N-метилглицинамид,
N-метил-N-{3-[2-(2-метил-6,7-дигидро[1,3]триазоло[5,4-c]пиридин-5(4H)-ил)пиримидин-5-ил]бензил}глицинамид,
N-{3-[2-(5,7-дигидро-6H-пирроло[3,4-b]пиридин-6-ил)пиримидин-5-ил]бензил}-N-метилглицинамид или
N-(3-{2-[(3S)-3-фторпирролидин-1-ил]пиримидин-5-ил}бензил)-N-метилглицинамид.
20. Фармацевтическая композиция, содержащая соединение или его соль по п.1 и фармацевтически приемлемый инертный наполнитель.
21. Фармацевтическая композиция для профилактики и/или лечения связанных с VAP-1 заболеваний, содержащая соединение или его соль по п.1.
22. Применение соединения или его соли по п.1 для получения фармацевтической композиции для профилактики и/или лечения связанных с VAP-1 заболеваний.
23. Применение соединения или его соли по п.1 для профилактики и/или лечения связанных с VAP-1 заболеваний.
24. Способ профилактики и/или лечения связанных с VAP-1 заболеваний, включающий введение пациенту эффективного количества соединения или его соли по п.1.
25. Соединение или его соль по п.1 для профилактики и/или лечения связанных с VAP-1 заболеваний.
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US8501739B2 (en) * | 2005-07-04 | 2013-08-06 | High Point Pharmaceuticals, Llc | Medicaments |
US20070066646A1 (en) | 2005-08-02 | 2007-03-22 | Genmedica Therapeutics Sl | Compounds for Inhibiting Copper-Containing Amine Oxidases and Uses Thereof |
US20090156646A1 (en) | 2005-08-11 | 2009-06-18 | Takeda Pharmaceutical Company Limited | Pyridylphenol compound and use thereof |
TW200813015A (en) | 2006-03-15 | 2008-03-16 | Mitsubishi Pharma Corp | 2-(cyclic amino)-pyrimidone derivatives |
WO2008104077A1 (en) | 2007-02-28 | 2008-09-04 | Methylgene Inc. | Small molecule inhibitors of protein arginine methyltransferases (prmts) |
WO2009055002A1 (en) | 2007-10-24 | 2009-04-30 | La Jolla Pharmaceutical Company | Combined inhibitors of cyclooxygenase and semicarbazide-sensitive amine oxidase (ssao) (vascular adhesion protein, vap-1) |
-
2010
- 2010-09-15 AU AU2010296420A patent/AU2010296420A1/en not_active Abandoned
- 2010-09-15 CA CA2772689A patent/CA2772689A1/en not_active Abandoned
- 2010-09-15 KR KR1020127004677A patent/KR20120083292A/ko not_active Application Discontinuation
- 2010-09-15 RU RU2012114846/04A patent/RU2012114846A/ru not_active Application Discontinuation
- 2010-09-15 PL PL10817191T patent/PL2479165T3/pl unknown
- 2010-09-15 ES ES10817191.9T patent/ES2651690T3/es active Active
- 2010-09-15 WO PCT/JP2010/065918 patent/WO2011034078A1/ja active Application Filing
- 2010-09-15 TW TW099131248A patent/TW201116276A/zh unknown
- 2010-09-15 JP JP2011531942A patent/JP5640983B2/ja not_active Expired - Fee Related
- 2010-09-15 US US13/394,505 patent/US8802679B2/en active Active
- 2010-09-15 MX MX2012003324A patent/MX2012003324A/es not_active Application Discontinuation
- 2010-09-15 BR BR112012006010A patent/BR112012006010A2/pt not_active IP Right Cessation
- 2010-09-15 PT PT108171919T patent/PT2479165T/pt unknown
- 2010-09-15 EP EP10817191.9A patent/EP2479165B1/en active Active
- 2010-09-15 CN CN201080041470.2A patent/CN102498091B/zh not_active Expired - Fee Related
-
2012
- 2012-02-27 ZA ZA2012/01437A patent/ZA201201437B/en unknown
- 2012-02-29 IL IL218394A patent/IL218394A0/en unknown
Also Published As
Publication number | Publication date |
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EP2479165A1 (en) | 2012-07-25 |
MX2012003324A (es) | 2012-04-30 |
ZA201201437B (en) | 2013-05-29 |
US8802679B2 (en) | 2014-08-12 |
EP2479165A4 (en) | 2013-02-27 |
EP2479165B1 (en) | 2017-10-25 |
KR20120083292A (ko) | 2012-07-25 |
TW201116276A (en) | 2011-05-16 |
JPWO2011034078A1 (ja) | 2013-02-14 |
CN102498091B (zh) | 2014-03-05 |
PT2479165T (pt) | 2017-12-19 |
ES2651690T3 (es) | 2018-01-29 |
CA2772689A1 (en) | 2011-03-24 |
JP5640983B2 (ja) | 2014-12-17 |
US20120184520A1 (en) | 2012-07-19 |
BR112012006010A2 (pt) | 2016-03-22 |
CN102498091A (zh) | 2012-06-13 |
PL2479165T3 (pl) | 2018-05-30 |
AU2010296420A1 (en) | 2012-03-22 |
IL218394A0 (en) | 2012-04-30 |
WO2011034078A1 (ja) | 2011-03-24 |
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