CA2730471C - Piperazine derivatives used as cav2.2 calcium channel modulators - Google Patents
Piperazine derivatives used as cav2.2 calcium channel modulators Download PDFInfo
- Publication number
- CA2730471C CA2730471C CA2730471A CA2730471A CA2730471C CA 2730471 C CA2730471 C CA 2730471C CA 2730471 A CA2730471 A CA 2730471A CA 2730471 A CA2730471 A CA 2730471A CA 2730471 C CA2730471 C CA 2730471C
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- CA
- Canada
- Prior art keywords
- methyl
- mmol
- compound
- trifluoromethyl
- pharmaceutically acceptable
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
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- 150000004885 piperazines Chemical class 0.000 title abstract description 4
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 title abstract description 4
- 108090000312 Calcium Channels Proteins 0.000 title abstract 2
- 102000003922 Calcium Channels Human genes 0.000 title abstract 2
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
- 150000001875 compounds Chemical class 0.000 claims description 273
- 229910052739 hydrogen Inorganic materials 0.000 claims description 68
- 239000001257 hydrogen Substances 0.000 claims description 67
- 150000003839 salts Chemical class 0.000 claims description 64
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 45
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 39
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 35
- 208000002193 Pain Diseases 0.000 claims description 29
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 29
- 230000036407 pain Effects 0.000 claims description 26
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 24
- 229910052757 nitrogen Inorganic materials 0.000 claims description 21
- 238000011282 treatment Methods 0.000 claims description 21
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- 150000002367 halogens Chemical class 0.000 claims description 20
- 239000003814 drug Substances 0.000 claims description 17
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 17
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 12
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 12
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 11
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 9
- 125000006661 (C4-C6) heterocyclic group Chemical group 0.000 claims description 9
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 8
- 125000002393 azetidinyl group Chemical group 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000002757 morpholinyl group Chemical group 0.000 claims description 6
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
- 125000001963 4 membered heterocyclic group Chemical group 0.000 claims description 3
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- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 150000002431 hydrogen Chemical group 0.000 claims 9
- BLFJGFDZMABYMY-ZDUSSCGKSA-N (2-methylpyridin-3-yl)-[(2s)-2-methyl-4-[4-(trifluoromethyl)phenyl]sulfonylpiperazin-1-yl]methanone Chemical compound C([C@@H]1C)N(S(=O)(=O)C=2C=CC(=CC=2)C(F)(F)F)CCN1C(=O)C1=CC=CN=C1C BLFJGFDZMABYMY-ZDUSSCGKSA-N 0.000 claims 2
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 129
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- 125000000217 alkyl group Chemical group 0.000 description 27
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- 229910052786 argon Inorganic materials 0.000 description 24
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- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 24
- 239000012458 free base Substances 0.000 description 22
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 21
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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
- C07D401/06—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
-
- 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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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
-
- 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
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms 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)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| GB0813142.7 | 2008-07-17 | ||
| GBGB0813142.7A GB0813142D0 (en) | 2008-07-17 | 2008-07-17 | Novel compounds |
| PCT/EP2009/059012 WO2010007073A1 (en) | 2008-07-17 | 2009-07-15 | Piperazine derivatives used as cav2.2 calcium channel modulators |
Publications (2)
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| CA2730471A1 CA2730471A1 (en) | 2010-01-21 |
| CA2730471C true CA2730471C (en) | 2016-12-06 |
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| Application Number | Title | Priority Date | Filing Date |
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| CA2730471A Expired - Fee Related CA2730471C (en) | 2008-07-17 | 2009-07-15 | Piperazine derivatives used as cav2.2 calcium channel modulators |
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| BR (1) | BRPI0916622A2 (enExample) |
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| EA (1) | EA018621B1 (enExample) |
| ES (2) | ES2396962T3 (enExample) |
| GB (1) | GB0813142D0 (enExample) |
| IL (1) | IL210446A (enExample) |
| MX (1) | MX2011000600A (enExample) |
| PL (1) | PL2300432T3 (enExample) |
| TW (1) | TW201016677A (enExample) |
| UY (1) | UY31990A (enExample) |
| WO (2) | WO2010007072A1 (enExample) |
| ZA (1) | ZA201100014B (enExample) |
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| GB0813142D0 (en) * | 2008-07-17 | 2008-08-27 | Glaxo Group Ltd | Novel compounds |
| GB201000685D0 (en) | 2010-01-15 | 2010-03-03 | Glaxo Group Ltd | Novel compounds |
| EP2665729B1 (en) * | 2011-01-19 | 2015-04-01 | Convergence Pharmaceuticals Limited | Piperazine derivatives as cav2.2 calcium channel blockers |
| CN103781759B (zh) | 2011-06-27 | 2016-01-13 | 纽朗制药有限公司 | 氟化的芳基烷基氨基甲酰胺衍生物 |
| EP3495360A1 (en) * | 2014-04-14 | 2019-06-12 | Grünenthal GmbH | Heteroaryl substituted heterocyclyl sulfones |
| US9896440B2 (en) | 2014-04-14 | 2018-02-20 | Grünenthal GmbH | Aryl substituted heterocyclyl sulfones |
| GB201516183D0 (en) * | 2015-09-14 | 2015-10-28 | Calchan Ltd | Novel pharmaceutical composition |
| TW201718557A (zh) | 2015-10-08 | 2017-06-01 | 歌林達有限公司 | 經吡唑基取代之四氫吡喃基碸 |
| TW201726128A (zh) | 2015-10-08 | 2017-08-01 | 歌林達有限公司 | 經吡唑基取代之四氫哌喃基碸 |
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| US5474995A (en) | 1993-06-24 | 1995-12-12 | Merck Frosst Canada, Inc. | Phenyl heterocycles as cox-2 inhibitors |
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| US5633272A (en) | 1995-02-13 | 1997-05-27 | Talley; John J. | Substituted isoxazoles for the treatment of inflammation |
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| IL117580A0 (en) | 1995-03-29 | 1996-07-23 | Merck & Co Inc | Inhibitors of farnesyl-protein transferase and pharmaceutical compositions containing them |
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| UA57002C2 (uk) | 1995-10-13 | 2003-06-16 | Мерк Фросст Кенада Енд Ко./Мерк Фросст Кенада Енд Сі. | Похідне (метилсульфоніл)феніл-2-(5н)-фуранону, фармацевтична композиція та спосіб лікування |
| FR2744450A1 (fr) | 1996-02-02 | 1997-08-08 | Pf Medicament | Nouvelles naphtylpiperazines derivees de cycloazanes substitues, ainsi que leur procede de preparation, les compositions pharmaceutiques et leur utilisation comme medicaments |
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| SI0912518T1 (en) | 1996-07-18 | 2003-12-31 | Merck Frosst Canada & Co. | Substituted pyridines as selective cyclooxygenase-2 inhibitors |
| WO1998017625A1 (en) | 1996-10-22 | 1998-04-30 | Daiichi Pharmaceutical Co., Ltd. | Novel remedies for infectious diseases |
| GB9623283D0 (en) | 1996-11-08 | 1997-01-08 | Zeneca Ltd | Heterocyclic derivatives |
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| UA59433C2 (uk) | 1998-01-27 | 2003-09-15 | Авентіс Фармасьютікалс Продактс Інк. | ЗАМІЩЕНІ ОКСОАЗАГЕТЕРОЦИКЛІЧНІ ІНГІБІТОРИ ФАКТОРА Хa ТА ПРОМІЖНІ СПОЛУКИ ДЛЯ ЇХ ОТРИМАННЯ |
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- 2009-07-15 TW TW098123842A patent/TW201016677A/zh unknown
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