CA2829803A1 - Morpholine-spirocyclic piperidine amides as modulators of ion channels - Google Patents
Morpholine-spirocyclic piperidine amides as modulators of ion channels Download PDFInfo
- Publication number
- CA2829803A1 CA2829803A1 CA2829803A CA2829803A CA2829803A1 CA 2829803 A1 CA2829803 A1 CA 2829803A1 CA 2829803 A CA2829803 A CA 2829803A CA 2829803 A CA2829803 A CA 2829803A CA 2829803 A1 CA2829803 A1 CA 2829803A1
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- Prior art keywords
- pain
- compound
- alkyl
- branched
- cyclic
- 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.)
- Abandoned
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- -1 piperidine amides Chemical class 0.000 title claims description 101
- 102000004310 Ion Channels Human genes 0.000 title abstract description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 212
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- 125000004122 cyclic group Chemical group 0.000 claims description 148
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 106
- 229910052717 sulfur Inorganic materials 0.000 claims description 78
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 76
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 71
- 125000005843 halogen group Chemical group 0.000 claims description 70
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 52
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 48
- 125000001072 heteroaryl group Chemical group 0.000 claims description 48
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 45
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- 229910052760 oxygen Inorganic materials 0.000 claims description 40
- 125000003118 aryl group Chemical group 0.000 claims description 38
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 31
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 30
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 29
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- 150000003839 salts Chemical class 0.000 claims description 25
- 102000018674 Sodium Channels Human genes 0.000 claims description 24
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 20
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- 125000002733 (C1-C6) fluoroalkyl group Chemical group 0.000 claims description 19
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- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 14
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- VUWZPRWSIVNGKG-UHFFFAOYSA-N fluoromethane Chemical compound F[CH2] VUWZPRWSIVNGKG-UHFFFAOYSA-N 0.000 claims description 11
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 10
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical class COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 10
- 206010044652 trigeminal neuralgia Diseases 0.000 claims description 10
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 9
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- 125000004429 atom Chemical group 0.000 claims description 9
- 125000002619 bicyclic group Chemical group 0.000 claims description 9
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 206010003591 Ataxia Diseases 0.000 claims description 8
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 claims description 8
- 108010081348 HRT1 protein Hairy Proteins 0.000 claims description 8
- 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 claims description 8
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- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 6
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 6
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- 208000013403 hyperactivity Diseases 0.000 claims description 6
- 208000015706 neuroendocrine disease Diseases 0.000 claims description 6
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 6
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- 208000004998 Abdominal Pain Diseases 0.000 claims description 5
- 208000027418 Wounds and injury Diseases 0.000 claims description 5
- 230000002757 inflammatory effect Effects 0.000 claims description 5
- 125000004043 oxo group Chemical group O=* 0.000 claims description 5
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 208000011580 syndromic disease Diseases 0.000 claims description 4
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- 206010033645 Pancreatitis Diseases 0.000 claims description 3
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- 208000000450 Pelvic Pain Diseases 0.000 claims description 3
- 208000010886 Peripheral nerve injury Diseases 0.000 claims description 3
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- 206010037596 Pyelonephritis Diseases 0.000 claims description 3
- 206010037779 Radiculopathy Diseases 0.000 claims description 3
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- 208000008548 Tension-Type Headache Diseases 0.000 claims description 3
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- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
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- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 2
- 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
- 125000004372 methylthioethyl group Chemical group [H]C([H])([H])SC([H])([H])C([H])([H])* 0.000 claims description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 230000001314 paroxysmal effect Effects 0.000 claims description 2
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
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- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/10—Spiro-condensed systems
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
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- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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| US8828996B2 (en) | 2014-09-09 |
| ES2618929T3 (es) | 2017-06-22 |
| WO2012125613A1 (en) | 2012-09-20 |
| MX2013010476A (es) | 2013-10-30 |
| EP2686325A1 (en) | 2014-01-22 |
| AU2012229187A1 (en) | 2013-09-19 |
| JP2014508169A (ja) | 2014-04-03 |
| CN103517910A (zh) | 2014-01-15 |
| US20120264749A1 (en) | 2012-10-18 |
| MX347982B (es) | 2017-05-22 |
| CN103517910B (zh) | 2016-12-14 |
| US20150025073A1 (en) | 2015-01-22 |
| EP2686325B1 (en) | 2016-12-14 |
| AU2012229187B2 (en) | 2016-11-10 |
| NZ615014A (en) | 2016-08-26 |
| JP6088443B2 (ja) | 2017-03-01 |
| US9181273B2 (en) | 2015-11-10 |
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