AU2008312636B2 - Substituted N-phenyl-pyrrolidinylmethylpyrrolidine amides and therapeutic use thereof as histamine H3 receptor modulators - Google Patents
Substituted N-phenyl-pyrrolidinylmethylpyrrolidine amides and therapeutic use thereof as histamine H3 receptor modulators Download PDFInfo
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- AU2008312636B2 AU2008312636B2 AU2008312636A AU2008312636A AU2008312636B2 AU 2008312636 B2 AU2008312636 B2 AU 2008312636B2 AU 2008312636 A AU2008312636 A AU 2008312636A AU 2008312636 A AU2008312636 A AU 2008312636A AU 2008312636 B2 AU2008312636 B2 AU 2008312636B2
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- Prior art keywords
- methyl
- pyrrolidin
- phenyl
- ylmethyl
- amide
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- -1 N-phenyl-pyrrolidinylmethylpyrrolidine amides Chemical class 0.000 title claims abstract description 87
- 102000004384 Histamine H3 receptors Human genes 0.000 title abstract description 26
- 108090000981 Histamine H3 receptors Proteins 0.000 title abstract description 26
- 230000001225 therapeutic effect Effects 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 135
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 40
- 238000000034 method Methods 0.000 claims abstract description 36
- 201000010099 disease Diseases 0.000 claims abstract description 28
- 238000002360 preparation method Methods 0.000 claims abstract description 11
- 238000011282 treatment Methods 0.000 claims abstract description 10
- 150000003839 salts Chemical class 0.000 claims description 41
- 125000000217 alkyl group Chemical group 0.000 claims description 26
- MHOBDNUWJRMSRF-UHFFFAOYSA-N 2-methyl-4-[3-[(2-methylpyrrolidin-1-yl)methyl]pyrrolidin-1-yl]aniline Chemical compound CC1CCCN1CC1CN(C=2C=C(C)C(N)=CC=2)CC1 MHOBDNUWJRMSRF-UHFFFAOYSA-N 0.000 claims description 21
- 239000000203 mixture Substances 0.000 claims description 18
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 208000035475 disorder Diseases 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
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- 125000001424 substituent group Chemical group 0.000 claims description 7
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 6
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- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 6
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- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 125000002883 imidazolyl group Chemical group 0.000 claims description 6
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- LVPMIMZXDYBCDF-UHFFFAOYSA-N isocinchomeronic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)N=C1 LVPMIMZXDYBCDF-UHFFFAOYSA-N 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 6
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 6
- JUTVIVDYDLACSP-UHFFFAOYSA-N 4-imidazol-1-yl-n-[2-methyl-4-[3-[(2-methylpyrrolidin-1-yl)methyl]pyrrolidin-1-yl]phenyl]benzamide Chemical compound CC1CCCN1CC1CN(C=2C=C(C)C(NC(=O)C=3C=CC(=CC=3)N3C=NC=C3)=CC=2)CC1 JUTVIVDYDLACSP-UHFFFAOYSA-N 0.000 claims description 5
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- FKNQXFIMZSMBLL-UHFFFAOYSA-N n-[2-methyl-4-[3-[(2-methylpyrrolidin-1-yl)methyl]pyrrolidin-1-yl]phenyl]-4-(3-methyl-5-oxo-4h-pyrazol-1-yl)benzamide Chemical compound CC1CCCN1CC1CN(C=2C=C(C)C(NC(=O)C=3C=CC(=CC=3)N3C(CC(C)=N3)=O)=CC=2)CC1 FKNQXFIMZSMBLL-UHFFFAOYSA-N 0.000 claims description 5
- JFCIRXKCYXZKKC-UHFFFAOYSA-N n-[2-methyl-4-[3-[(2-methylpyrrolidin-1-yl)methyl]pyrrolidin-1-yl]phenyl]-6-(phenylmethoxymethyl)pyridine-3-carboxamide Chemical compound CC1CCCN1CC1CN(C=2C=C(C)C(NC(=O)C=3C=NC(COCC=4C=CC=CC=4)=CC=3)=CC=2)CC1 JFCIRXKCYXZKKC-UHFFFAOYSA-N 0.000 claims description 5
- FKPVLOBWGQUIAM-UHFFFAOYSA-N n-[2-methyl-4-[3-[(2-methylpyrrolidin-1-yl)methyl]pyrrolidin-1-yl]phenyl]-6-pyrrol-1-ylpyridine-3-carboxamide Chemical compound CC1CCCN1CC1CN(C=2C=C(C)C(NC(=O)C=3C=NC(=CC=3)N3C=CC=C3)=CC=2)CC1 FKPVLOBWGQUIAM-UHFFFAOYSA-N 0.000 claims description 5
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 5
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- GTJIDFLZYALYBZ-VQTJNVASSA-N 5-fluoro-2-methyl-n-[2-methyl-4-[(3r)-3-[[(2s)-2-methylpyrrolidin-1-yl]methyl]pyrrolidin-1-yl]phenyl]benzamide Chemical compound C[C@H]1CCCN1C[C@@H]1CN(C=2C=C(C)C(NC(=O)C=3C(=CC=C(F)C=3)C)=CC=2)CC1 GTJIDFLZYALYBZ-VQTJNVASSA-N 0.000 claims description 4
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- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
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Classifications
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- 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
- C07D401/12—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 chain containing hetero atoms as chain links
-
- 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
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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
-
- 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
- A61P25/24—Antidepressants
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
- C07D207/09—Radicals substituted by 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
- C07D401/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 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
- C07D405/02—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
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
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- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (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)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyrrole Compounds (AREA)
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| US60/980,602 | 2007-10-17 | ||
| PCT/US2008/079758 WO2009052063A1 (en) | 2007-10-17 | 2008-10-14 | Substituted n-phenyl-pyrrolidinylmethylpyrrolidine amides and therapeutic use thereof as histamine h3 receptor modulators |
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| AU2008312636A1 AU2008312636A1 (en) | 2009-04-23 |
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| EP (1) | EP2205558B1 (enExample) |
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| MX (1) | MX2010004003A (enExample) |
| MY (1) | MY150210A (enExample) |
| NZ (1) | NZ584691A (enExample) |
| PT (1) | PT2205558E (enExample) |
| RU (1) | RU2477721C2 (enExample) |
| WO (1) | WO2009052063A1 (enExample) |
| ZA (1) | ZA201002113B (enExample) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE525351T1 (de) | 2007-10-17 | 2011-10-15 | Sanofi Sa | Substituierte n-phenyl- bipyrrolidincarbonsäureamide und deren therapeutische verwendung |
| CA2702482C (en) | 2007-10-17 | 2012-11-27 | Sanofi-Aventis | Substituted n-phenyl-bipyrrolidine carboxamides and therapeutic use thereof |
| PL2215058T3 (pl) | 2007-10-17 | 2012-04-30 | Sanofi Sa | Podstawione N-fenylo-bipirolidynomoczniki oraz ich zastosowanie terapeutyczne |
| AR074467A1 (es) | 2008-12-05 | 2011-01-19 | Sanofi Aventis | Tetrahidropiran espiro pirrolidinonas y piperidinonas sustituidas, composiciones farmaceuticas que las contienen y uso de las mismas en el tratamiento y/o prevencion de enfermedades del snc ,tales como alzheimer y parkinson, entre otras. |
| AR074466A1 (es) * | 2008-12-05 | 2011-01-19 | Sanofi Aventis | Piperidina espiro pirrolidinona y piperidinona sustituidas y su uso terapeutico en enfermedades mediadas por la modulacion de los receptores h3. |
| EP2569294B1 (en) | 2010-05-11 | 2015-03-11 | Sanofi | Substituted n-heteroaryl bipyrrolidine carboxamides, preparation and therapeutic use thereof |
| WO2011143145A1 (en) | 2010-05-11 | 2011-11-17 | Sanofi | Substituted n-alkyl and n-acyl tetrahydro-isoquinoline derivatives, preparation and therapeutic use thereof |
| EP2569280B1 (en) | 2010-05-11 | 2015-02-25 | Sanofi | Substituted phenyl cycloalkyl pyrrolidine (piperidine) spirolactams and amides, preparation and therapeutic use thereof |
| TW201206444A (en) | 2010-05-11 | 2012-02-16 | Sanofi Aventis | Substituted N-heteroaryl tetrahydro-isoquinoline derivatives, preparation and therapeutic use thereof |
| TW201202251A (en) | 2010-05-11 | 2012-01-16 | Sanofi Aventis | Substituted N-heteroaryl spirolactam bipyrrolidines, preparation and therapeutic use thereof |
| JP2013529198A (ja) | 2010-05-11 | 2013-07-18 | サノフイ | 置換されたｎ−ヘテロシクロアルキルビピロリジニルフェニルアミド誘導体、その製造及び治療上の使用 |
| RU2562461C1 (ru) * | 2014-04-30 | 2015-09-10 | Федеральное государственное бюджетное учреждение науки Новосибирский институт органической химии им. Н.Н. Ворожцова Сибирского отделения Российской академии наук (НИОХ СО РАН) | Спин-меченое производное кинуренина и способ его получения |
Citations (1)
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|---|---|---|---|---|
| WO2004037257A1 (en) * | 2002-10-23 | 2004-05-06 | Janssen Pharmaceutica, N.V. | Phenylpiperidines and phenylpyrrolidines as histamine h3 receptor modulators |
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| PE20020507A1 (es) * | 2000-10-17 | 2002-06-25 | Schering Corp | Compuestos no-imidazoles como antagonistas del receptor histamina h3 |
| DE10306250A1 (de) * | 2003-02-14 | 2004-09-09 | Aventis Pharma Deutschland Gmbh | Substituierte N-Arylheterozyklen, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| US7223788B2 (en) * | 2003-02-14 | 2007-05-29 | Sanofi-Aventis Deutschland Gmbh | Substituted N-aryl heterocycles, process for their preparation and their use as medicaments |
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2008
- 2008-10-14 WO PCT/US2008/079758 patent/WO2009052063A1/en not_active Ceased
- 2008-10-14 NZ NZ584691A patent/NZ584691A/en not_active IP Right Cessation
- 2008-10-14 RU RU2010119530/04A patent/RU2477721C2/ru not_active IP Right Cessation
- 2008-10-14 BR BRPI0818766 patent/BRPI0818766A2/pt not_active IP Right Cessation
- 2008-10-14 CA CA2702834A patent/CA2702834C/en not_active Expired - Fee Related
- 2008-10-14 DK DK08839706.2T patent/DK2205558T3/da active
- 2008-10-14 PT PT08839706T patent/PT2205558E/pt unknown
- 2008-10-14 MX MX2010004003A patent/MX2010004003A/es active IP Right Grant
- 2008-10-14 EP EP08839706A patent/EP2205558B1/en active Active
- 2008-10-14 KR KR1020107010710A patent/KR20100092443A/ko not_active Ceased
- 2008-10-14 MY MYPI2010001275A patent/MY150210A/en unknown
- 2008-10-14 AU AU2008312636A patent/AU2008312636B2/en not_active Ceased
- 2008-10-14 ES ES08839706T patent/ES2392122T3/es active Active
- 2008-10-14 CN CN2008801212575A patent/CN101903342B/zh not_active Expired - Fee Related
- 2008-10-14 JP JP2010530050A patent/JP5377504B2/ja not_active Expired - Fee Related
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2010
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- 2010-03-25 ZA ZA2010/02113A patent/ZA201002113B/en unknown
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- 2010-05-17 MA MA32849A patent/MA31857B1/fr unknown
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| WO2004037257A1 (en) * | 2002-10-23 | 2004-05-06 | Janssen Pharmaceutica, N.V. | Phenylpiperidines and phenylpyrrolidines as histamine h3 receptor modulators |
Also Published As
| Publication number | Publication date |
|---|---|
| MY150210A (en) | 2013-12-13 |
| MA31857B1 (fr) | 2010-11-01 |
| CA2702834C (en) | 2013-01-15 |
| KR20100092443A (ko) | 2010-08-20 |
| AU2008312636A1 (en) | 2009-04-23 |
| HK1146055A1 (en) | 2011-05-13 |
| WO2009052063A1 (en) | 2009-04-23 |
| IL205000A0 (en) | 2010-11-30 |
| MX2010004003A (es) | 2010-04-30 |
| CN101903342B (zh) | 2012-11-21 |
| ZA201002113B (en) | 2010-12-29 |
| EP2205558B1 (en) | 2012-07-25 |
| US20100173898A1 (en) | 2010-07-08 |
| RU2477721C2 (ru) | 2013-03-20 |
| PT2205558E (pt) | 2012-11-02 |
| ES2392122T3 (es) | 2012-12-04 |
| JP5377504B2 (ja) | 2013-12-25 |
| NZ584691A (en) | 2011-09-30 |
| CA2702834A1 (en) | 2009-04-23 |
| CN101903342A (zh) | 2010-12-01 |
| BRPI0818766A2 (pt) | 2015-04-14 |
| RU2010119530A (ru) | 2011-11-27 |
| JP2011500694A (ja) | 2011-01-06 |
| US8227504B2 (en) | 2012-07-24 |
| DK2205558T3 (da) | 2012-11-05 |
| EP2205558A1 (en) | 2010-07-14 |
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