RU2016132858A - Производные фторнафтила - Google Patents
Производные фторнафтила Download PDFInfo
- Publication number
- RU2016132858A RU2016132858A RU2016132858A RU2016132858A RU2016132858A RU 2016132858 A RU2016132858 A RU 2016132858A RU 2016132858 A RU2016132858 A RU 2016132858A RU 2016132858 A RU2016132858 A RU 2016132858A RU 2016132858 A RU2016132858 A RU 2016132858A
- Authority
- RU
- Russia
- Prior art keywords
- fluoro
- methyl
- naphthamide
- hydroxytetrahydro
- pyran
- Prior art date
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- 229910052731 fluorine Inorganic materials 0.000 title 1
- 239000011737 fluorine Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 15
- 208000024827 Alzheimer disease Diseases 0.000 claims 5
- 208000028698 Cognitive impairment Diseases 0.000 claims 5
- 208000010877 cognitive disease Diseases 0.000 claims 5
- 201000000980 schizophrenia Diseases 0.000 claims 5
- 208000019116 sleep disease Diseases 0.000 claims 5
- 208000002193 Pain Diseases 0.000 claims 4
- 208000022925 sleep disturbance Diseases 0.000 claims 4
- 125000001424 substituent group Chemical group 0.000 claims 4
- 125000000217 alkyl group Chemical group 0.000 claims 3
- 238000011282 treatment Methods 0.000 claims 3
- ODFVXVSVXQOSMG-PMACEKPBSA-N 4-[(6-chloropyridin-3-yl)methyl]-1-fluoro-N-[(1S,2S)-2-hydroxycyclohexyl]naphthalene-2-carboxamide Chemical compound ClC1=CC=C(C=N1)CC1=CC(=C(C2=CC=CC=C12)F)C(=O)N[C@@H]1[C@H](CCCC1)O ODFVXVSVXQOSMG-PMACEKPBSA-N 0.000 claims 2
- 239000013543 active substance Substances 0.000 claims 2
- 239000002671 adjuvant Substances 0.000 claims 2
- 125000003545 alkoxy group Chemical group 0.000 claims 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
- 125000003386 piperidinyl group Chemical group 0.000 claims 2
- 125000004076 pyridyl group Chemical group 0.000 claims 2
- GFRKKRCGBSUEOH-DQEYMECFSA-N 1-fluoro-4-[[2-fluoro-4-(1-methylpyrazol-4-yl)phenyl]methyl]-N-[(3R,4S)-3-hydroxyoxan-4-yl]naphthalene-2-carboxamide Chemical compound CN1C=C(C=N1)C1=CC(F)=C(CC2=CC(C(=O)N[C@H]3CCOC[C@@H]3O)=C(F)C3=CC=CC=C23)C=C1 GFRKKRCGBSUEOH-DQEYMECFSA-N 0.000 claims 1
- DQZKNHZVLILHDP-LBNVMWSVSA-N 1-fluoro-N-[(1S,2R)-2-hydroxy-2-methylcyclohexyl]-4-[[6-(1-methylpyrazol-4-yl)pyridin-3-yl]methyl]naphthalene-2-carboxamide Chemical compound CN1C=C(C=N1)C1=CC=C(CC2=CC(C(=O)N[C@H]3CCCC[C@@]3(C)O)=C(F)C3=CC=CC=C23)C=N1 DQZKNHZVLILHDP-LBNVMWSVSA-N 0.000 claims 1
- UGZZENFWEFVTRF-VXKWHMMOSA-N 1-fluoro-N-[(1S,2S)-2-hydroxycyclohexyl]-4-[(6-methylpyridin-3-yl)methyl]naphthalene-2-carboxamide Chemical compound CC1=CC=C(CC2=CC(C(=O)N[C@H]3CCCC[C@@H]3O)=C(F)C3=CC=CC=C23)C=N1 UGZZENFWEFVTRF-VXKWHMMOSA-N 0.000 claims 1
- BWTRBPPXLSBFLR-DQEYMECFSA-N 1-fluoro-N-[(1S,2S)-2-hydroxycyclohexyl]-4-[[6-(1-methylpyrazol-4-yl)pyridin-3-yl]methyl]naphthalene-2-carboxamide Chemical compound CN1C=C(C=N1)C1=CC=C(CC2=CC(C(=O)N[C@H]3CCCC[C@@H]3O)=C(F)C3=CC=CC=C23)C=N1 BWTRBPPXLSBFLR-DQEYMECFSA-N 0.000 claims 1
- MOTLFEFHDFLBQO-VXKWHMMOSA-N 1-fluoro-N-[(3R,4S)-3-hydroxyoxan-4-yl]-4-[(4-methylphenyl)methyl]naphthalene-2-carboxamide Chemical compound CC1=CC=C(CC2=CC(C(=O)N[C@H]3CCOC[C@@H]3O)=C(F)C3=CC=CC=C23)C=C1 MOTLFEFHDFLBQO-VXKWHMMOSA-N 0.000 claims 1
- AEEAFUBVHJXXNM-DQEYMECFSA-N 1-fluoro-N-[(3R,4S)-3-hydroxyoxan-4-yl]-4-[[4-(1-methylpyrazol-4-yl)phenyl]methyl]naphthalene-2-carboxamide Chemical compound CN1C=C(C=N1)C1=CC=C(CC2=CC(C(=O)N[C@H]3CCOC[C@@H]3O)=C(F)C3=CC=CC=C23)C=C1 AEEAFUBVHJXXNM-DQEYMECFSA-N 0.000 claims 1
- NZMSZBWQPZHKMS-SFTDATJTSA-N 1-fluoro-N-[(3R,4S)-3-hydroxyoxan-4-yl]-4-[[4-(trifluoromethoxy)phenyl]methyl]naphthalene-2-carboxamide Chemical compound O[C@H]1COCC[C@@H]1NC(=O)C1=C(F)C2=CC=CC=C2C(CC2=CC=C(OC(F)(F)F)C=C2)=C1 NZMSZBWQPZHKMS-SFTDATJTSA-N 0.000 claims 1
- PQZBCCGOIMNBLV-ZEQRLZLVSA-N 1-fluoro-N-[(3R,4S)-3-hydroxyoxan-4-yl]-4-[[6-(1-methylpyrazol-4-yl)pyridin-3-yl]methyl]naphthalene-2-carboxamide Chemical compound CN1C=C(C=N1)C1=CC=C(CC2=CC(C(=O)N[C@H]3CCOC[C@@H]3O)=C(F)C3=CC=CC=C23)C=N1 PQZBCCGOIMNBLV-ZEQRLZLVSA-N 0.000 claims 1
- PQZBCCGOIMNBLV-DNQXCXABSA-N 1-fluoro-N-[(3S,4R)-3-hydroxyoxan-4-yl]-4-[[6-(1-methylpyrazol-4-yl)pyridin-3-yl]methyl]naphthalene-2-carboxamide Chemical compound CN1C=C(C=N1)C1=CC=C(CC2=CC(C(=O)N[C@@H]3CCOC[C@H]3O)=C(F)C3=CC=CC=C23)C=N1 PQZBCCGOIMNBLV-DNQXCXABSA-N 0.000 claims 1
- LTAVPOIOWAMMGH-ZEQRLZLVSA-N 1-fluoro-N-[(3S,4S)-4-hydroxyoxan-3-yl]-4-[[6-(1-methylpyrazol-4-yl)pyridin-3-yl]methyl]naphthalene-2-carboxamide Chemical compound CN1C=C(C=N1)C1=CC=C(CC2=CC(C(=O)N[C@H]3COCC[C@@H]3O)=C(F)C3=CC=CC=C23)C=N1 LTAVPOIOWAMMGH-ZEQRLZLVSA-N 0.000 claims 1
- PPESFTAATAFJTR-SFTDATJTSA-N 4-[(4-chlorophenyl)methyl]-1-fluoro-N-[(3R,4S)-3-hydroxyoxan-4-yl]naphthalene-2-carboxamide Chemical compound O[C@H]1COCC[C@@H]1NC(=O)C1=C(F)C2=CC=CC=C2C(CC2=CC=C(Cl)C=C2)=C1 PPESFTAATAFJTR-SFTDATJTSA-N 0.000 claims 1
- VMJJGOKGXBMAEQ-DQEYMECFSA-N 4-[(4-cyano-4-pyridin-2-ylpiperidin-1-yl)methyl]-1-fluoro-N-[(1S,2S)-2-hydroxycyclohexyl]naphthalene-2-carboxamide Chemical compound C(#N)C1(CCN(CC1)CC1=CC(=C(C2=CC=CC=C12)F)C(=O)N[C@@H]1[C@H](CCCC1)O)C1=NC=CC=C1 VMJJGOKGXBMAEQ-DQEYMECFSA-N 0.000 claims 1
- JEEWUVRTVKDADJ-VXKWHMMOSA-N 4-[(4-cyanophenyl)methyl]-1-fluoro-N-[(3R,4S)-3-hydroxyoxan-4-yl]naphthalene-2-carboxamide Chemical compound O[C@H]1COCC[C@@H]1NC(=O)C1=C(F)C2=CC=CC=C2C(CC2=CC=C(C=C2)C#N)=C1 JEEWUVRTVKDADJ-VXKWHMMOSA-N 0.000 claims 1
- XWKJCKAMJNNLCF-GBXCKJPGSA-N 4-[(6-chloropyridin-3-yl)methyl]-1-fluoro-N-[(1S,2R)-2-hydroxy-2-methylcyclohexyl]naphthalene-2-carboxamide Chemical compound C[C@@]1(O)CCCC[C@@H]1NC(=O)C1=C(F)C2=CC=CC=C2C(CC2=CC=C(Cl)N=C2)=C1 XWKJCKAMJNNLCF-GBXCKJPGSA-N 0.000 claims 1
- ODFVXVSVXQOSMG-VQTJNVASSA-N 4-[(6-chloropyridin-3-yl)methyl]-1-fluoro-N-[(1S,2R)-2-hydroxycyclohexyl]naphthalene-2-carboxamide Chemical compound O[C@@H]1CCCC[C@@H]1NC(=O)C1=C(F)C2=CC=CC=C2C(CC2=CC=C(Cl)N=C2)=C1 ODFVXVSVXQOSMG-VQTJNVASSA-N 0.000 claims 1
- SMSZCNQHXQSDRG-RBUKOAKNSA-N 4-[(6-chloropyridin-3-yl)methyl]-1-fluoro-N-[(1S,2R)-2-hydroxycyclopentyl]naphthalene-2-carboxamide Chemical compound ClC1=CC=C(C=N1)CC1=CC(=C(C2=CC=CC=C12)F)C(=O)N[C@@H]1[C@@H](CCC1)O SMSZCNQHXQSDRG-RBUKOAKNSA-N 0.000 claims 1
- XWKJCKAMJNNLCF-RDPSFJRHSA-N 4-[(6-chloropyridin-3-yl)methyl]-1-fluoro-N-[(1S,2S)-2-hydroxy-2-methylcyclohexyl]naphthalene-2-carboxamide Chemical compound C[C@]1(O)CCCC[C@@H]1NC(=O)C1=C(F)C2=CC=CC=C2C(CC2=CC=C(Cl)N=C2)=C1 XWKJCKAMJNNLCF-RDPSFJRHSA-N 0.000 claims 1
- SMSZCNQHXQSDRG-OALUTQOASA-N 4-[(6-chloropyridin-3-yl)methyl]-1-fluoro-N-[(1S,2S)-2-hydroxycyclopentyl]naphthalene-2-carboxamide Chemical compound ClC1=CC=C(C=N1)CC1=CC(=C(C2=CC=CC=C12)F)C(=O)N[C@@H]1[C@H](CCC1)O SMSZCNQHXQSDRG-OALUTQOASA-N 0.000 claims 1
- WVNGUCNMXDHLNG-OALUTQOASA-N 4-[(6-chloropyridin-3-yl)methyl]-1-fluoro-N-[(3R,4S)-3-hydroxyoxan-4-yl]naphthalene-2-carboxamide Chemical compound ClC1=CC=C(C=N1)CC1=CC(=C(C2=CC=CC=C12)F)C(=O)N[C@@H]1[C@H](COCC1)O WVNGUCNMXDHLNG-OALUTQOASA-N 0.000 claims 1
- WVNGUCNMXDHLNG-RTBURBONSA-N 4-[(6-chloropyridin-3-yl)methyl]-1-fluoro-N-[(3S,4R)-3-hydroxyoxan-4-yl]naphthalene-2-carboxamide Chemical compound ClC1=CC=C(C=N1)CC1=CC(=C(C2=CC=CC=C12)F)C(=O)N[C@H]1[C@@H](COCC1)O WVNGUCNMXDHLNG-RTBURBONSA-N 0.000 claims 1
- OCZBYPSETUGCDU-OALUTQOASA-N 4-[(6-chloropyridin-3-yl)methyl]-1-fluoro-N-[(3S,4S)-4-hydroxyoxan-3-yl]naphthalene-2-carboxamide Chemical compound ClC1=CC=C(C=N1)CC1=CC(=C(C2=CC=CC=C12)F)C(=O)N[C@H]1COCC[C@@H]1O OCZBYPSETUGCDU-OALUTQOASA-N 0.000 claims 1
- ZMXFQJRULXTKRX-ZEQRLZLVSA-N 4-[(6-cyclopropylpyridin-3-yl)methyl]-1-fluoro-N-[(1S,2S)-2-hydroxycyclohexyl]naphthalene-2-carboxamide Chemical compound C1(CC1)C1=CC=C(C=N1)CC1=CC(=C(C2=CC=CC=C12)F)C(=O)N[C@@H]1[C@H](CCCC1)O ZMXFQJRULXTKRX-ZEQRLZLVSA-N 0.000 claims 1
- BDKPRIJUCGZDNC-SFTDATJTSA-N 4-benzyl-1-fluoro-N-[(3R,4S)-3-hydroxyoxan-4-yl]naphthalene-2-carboxamide Chemical compound O[C@H]1COCC[C@@H]1NC(=O)C1=C(F)C2=CC=CC=C2C(CC2=CC=CC=C2)=C1 BDKPRIJUCGZDNC-SFTDATJTSA-N 0.000 claims 1
- 208000027520 Somatoform disease Diseases 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 125000004093 cyano group Chemical group *C#N 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- 125000001072 heteroaryl group Chemical group 0.000 claims 1
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 230000003287 optical effect Effects 0.000 claims 1
- 208000027753 pain disease Diseases 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 238000011321 prophylaxis Methods 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4433—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with oxygen as a ring hetero atom
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—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
- C07D213/56—Amides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen 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
- C07D213/61—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D309/14—Nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Anesthesiology (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
- Pyrane Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Claims (46)
1. Соединение формулы I
где:
R1 представляет собой С4-6-циклоалкил или С4-6-гетероциклоалкил, которые необязательно замещены одним или двумя заместителями, выбранными из гидроксила или низшего алкила;
А представляет собой фенил, пиридинил или пиперидинил;
R2 представляет собой атом водорода, атом галогена, низший алкил, цианогруппу, С4-6-циклоалкил, низшую алкоксигруппу, низшую алкоксигруппу, замещенную галогеном или является пяти- или шестичленной гетероарильной группой, необязательно замещенной низшей алкильной группой;
n равно 1 или 2;
или его фармацевтически приемлемая соль присоединения кислоты, рацемическая смесь или соответствующий энантиомер и/или оптический изомер.
2. Соединение формулы I по п. 1, отличающееся тем, что А представляет собой фенил, а другие заместители являются такими, как определено в п. 1.
3. Соединение формулы I, выбранное из:
1-фтор-N-((3RS,4SR)-3-гидрокситетрагидро-2Н-пиран-4-ил)-4-(4-метилбензил)-2-нафтамид;
4-бензил-1-фтор-N-((3RS,4SR)-3-гидрокситетрагидро-2Н-пиран-4-ил)-2-нафтамид;
4-(4-хлорбензил)-1-фтор-N-((3RS,4SR)-3-гидрокситетрагидро-2Н-пиран-4-ил)-2-нафтамид;
4-(4-цианобензил)-1-фтор-N-((3RS,4SR)-3-гидрокситетрагидро-2Н-пиран-4-ил)-2-нафтамид;
1-фтор-4-(2-фтор-4-(1-метил-1Н-пиразол-4-ил)бензил)-N-((3RS,4SR)-3-гидрокситетрагидро-2Н-пиран-4-ил)-2-нафтамид;
1-фтор-N-((3RS,4SR)-3-гидрокситетрагидро-2Н-пиран-4-ил)-4-(4-(трифторметокси)бензил)-2-нафтамид или
1-фтор-N-((3RS,4SR)-3-гидрокситетрагидро-2Н-пиран-4-ил)-4-(4-(1-метил-1Н-пиразол-4-ил)бензил)-2-нафтамид.
4. Соединение формулы I по п. 1, отличающееся тем, что А представляет собой пиридинил, а другие заместители являются такими, как определено в п. 1.
5. Соединение формулы I выбранное из:
4-((6-хлорипиридин-3-ил)метил)-1-фтор-N-((1SR,2SR)-2-гидроксициклогексил)-2-нафтамид;
4-((6-хлорпиридин-3-ил)метил)-1-фтор-N-((3RS,4SR)-3-гидрокситетрагидро-2Н-пиран-4-ил)-2-нафтамид;
4-((6-хлорпиридин-3-ил)метил)-1-фтор-N-((1S,2S)-2-гидроксициклогексил)-2-нафтамид;
4-((6-хлорпиридин-3-ил)метил)-1-фтор-N-((3S,4S)-4-гидрокситетрагидро-2Н-пиран-3-ил)-2-нафтамид;
4-((6-хлорпиридин-3-ил)метил)-1-фтор-N-((1S,2S)-2-гидроксициклопентил)-2-нафтамид;
4-((6-хлорипиридин-3-ил)метил)-1-фтор-N-((1S,2R)-2-гидроксициклопентил)-2-нафтамид;
4-((6-хлорпиридин-3-ил)метил)-1-фтор-N-((1SR,2SR)-2-гидрокси-2-метилциклогексил)-2-нафтамид;
4-((6-хлорпиридин-3-ил)метил)-1-фтор-N-((1SR,2RS)-2-гидрокси-2-метилциклогексил)-2-нафтамид;
4-((6-хлорпиридин-3-ил)метил)-1-фтор-N-((1SR,2RS)-2-гидроксициклогексил)-2-нафтамид;
1-фтор-N-((1S,2S)-2-гидроксициклогексил)-4-((6-(1-метил-1Н-пиразол-4-ил)пиридин-3-ил)метил)-2-нафтамид;
1-фтор-N-((3RS,4SR)-3-гидрокситетрагидро-2Н-пиран-4-ил)-4-((6-(1-метил-1Н-пиразол-4-ил)пиридин-3-ил)метил)-2-нафтамид;
1-фтор-N-[(3S,4R)-3-гидрокситетрагидропиран-4-ил]-4-[[6-(1-метилпиразол-4-ил)-3-пиридил]метил]нафталин-2-карбоксамид;
1-фтор-N-[(3R,4S)-3-гидрокситетрагидропиран-4-ил]-4-[[6-(1-метилпиразол-4-ил)-3-пиридил]метил]нафталин-2-карбоксамид;
1-фтор-N-((3S,4S)-4-гидрокситетрагидро-2Н-пиран-3-ил)-4-((6-(1-метил-1Н-пиразол-4-ил)пиридин-3-ил)метил)-2-нафтамид;
1-фтор-N-((1SR,2RS)-2-гидрокси-2-метилциклогексил)-4-((6-(1-метил-1Н-пиразол-4-ил)пиридин-3-ил)метил)-2-нафтамид;
1-фтор-N-((1SR,2SR)-2-гидроксициклогексил)-4-((6-метилпиридин-3-ил)метил)-2-нафтамид;
4-((6-циклопропилпиридин-3-ил)метил)-1-фтор-N-((1S,2S)-2-гидроксициклогексил)-2-нафтамид;
4-[(6-хлорпиридин-3-ил)метил]-1-фтор-N-[(3S,4R)-3-гидроксиоксан-4-ил]нафталин-2-карбоксамид.
6. Соединение формулы I по п. 1, отличающееся тем, что А представляет собой пиперидинил, а другие заместители являются такими, как определено в п. 1.
7. Соединение формулы I по п. 6, отличающееся тем, что этим соединением является 4-((4-циано-4-(пиридин-2-ил)пиперидин-1-ил)метил)-1-фтор-N-((1S,2S)-2-гидроксициклогексил)-2-нафтамид.
8. Фармацевтическая композиция, содержащая соединение по любому из пп. 1-7 и фармацевтически приемлемый носитель и/или адъювант.
9. Фармацевтическая композиция, содержащая соединение по любому из пп. 1-7 и фармацевтически приемлемый носитель и/или адъювант для применения для лечения болезни Альцгеймера, когнитивных нарушений, шизофрении, болей или нарушений сна.
10. Соединения по любому из пп. 1-7 для применения в качестве терапевтически активных веществ.
11. Соединения по любому из пп. 1-7 для применения в качестве терапевтически активных веществ для лечения болезни Альцгеймера, когнитивных нарушений, шизофрении, болей или нарушений сна.
12. Применение соединения по любому из пп. 1-7 для получения лекарственных средств для терапевтического и/или профилактического лечения болезни Альцгеймера, когнитивных нарушений, шизофрении, болей или нарушений сна.
13. Способ лечения или профилактики болезни Альцгеймера, когнитивных нарушений, шизофрении, болей или нарушений сна, который включает введение эффективного количества соединения по любому из пп. 1-7.
14. Применение соединения по любому из пп. 1-7 для лечения или профилактики болезни Альцгеймера, когнитивных нарушений, шизофрении, болей или нарушений сна.
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| EP14152124 | 2014-01-22 | ||
| EP14152124.5 | 2014-01-22 | ||
| PCT/EP2015/050830 WO2015110370A1 (en) | 2014-01-22 | 2015-01-19 | Fluoro-naphthyl derivatives |
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| US (1) | US9708302B2 (ru) |
| EP (1) | EP3097094B1 (ru) |
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| KR (1) | KR20160098500A (ru) |
| CN (1) | CN105793259A (ru) |
| CA (1) | CA2930961A1 (ru) |
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| JP6860551B2 (ja) | 2016-03-11 | 2021-04-14 | 武田薬品工業株式会社 | 芳香環化合物 |
| LT3507289T (lt) | 2016-09-02 | 2020-10-12 | Suven Life Sciences Limited | Muskarininio m1 receptoriaus atžvilgiu teigiami alosteriniai moduliatoriai |
| WO2018063552A1 (en) | 2016-09-30 | 2018-04-05 | Vanderbilt University | Positive allosteric modulators of the muscarinic acetylcholine receptor m1 |
| EA035599B1 (ru) * | 2017-04-13 | 2020-07-14 | Сувен Лайф Сайенсиз Лимитед | Позитивные аллостерические модуляторы мускариновых m1-рецепторов |
| US12298319B2 (en) | 2017-05-19 | 2025-05-13 | Takeda Pharmaceutical Company Limited | Method for measuring alpha value of muscarinic M1 receptor positive allosteric modulators |
| MX2020004339A (es) * | 2017-10-27 | 2020-08-03 | Suven Life Sciences Ltd | Moduladores alostericos positivos del receptor m1 muscarinico. |
| MA53917A (fr) | 2018-10-17 | 2022-01-26 | Suven Life Sciences Ltd | Dérivés de pyrrolo-pyridazine en tant que modulateurs allostériques positifs du récepteur m1 muscarinique |
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| JPWO2010090305A1 (ja) * | 2009-02-09 | 2012-08-09 | アステラス製薬株式会社 | 置換アシルグアニジン誘導体 |
| HRP20160574T1 (hr) * | 2009-12-17 | 2016-06-17 | Merck Sharp & Dohme Corp. | Pozitivni alosterni modulatori m1 receptora na bazi hinolin amida |
| EP2575454B1 (en) * | 2010-05-28 | 2018-08-29 | Merck Sharp & Dohme Corp. | Naphthalene carboxamide m1 receptor positive allosteric modulators |
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| CN105793259A (zh) | 2016-07-20 |
| EP3097094A1 (en) | 2016-11-30 |
| US20160326144A1 (en) | 2016-11-10 |
| JP6271758B2 (ja) | 2018-01-31 |
| JP2017501233A (ja) | 2017-01-12 |
| US9708302B2 (en) | 2017-07-18 |
| WO2015110370A1 (en) | 2015-07-30 |
| EP3097094B1 (en) | 2020-01-15 |
| HK1223919A1 (zh) | 2017-08-11 |
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