WO2005068448A1 - Sulfonamides a action antagoniste sur des canaux calcium de type n - Google Patents

Sulfonamides a action antagoniste sur des canaux calcium de type n Download PDF

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Publication number
WO2005068448A1
WO2005068448A1 PCT/GB2004/003705 GB2004003705W WO2005068448A1 WO 2005068448 A1 WO2005068448 A1 WO 2005068448A1 GB 2004003705 W GB2004003705 W GB 2004003705W WO 2005068448 A1 WO2005068448 A1 WO 2005068448A1
Authority
WO
WIPO (PCT)
Prior art keywords
alkyl
amino
piperidine
alkenyl
carbocyclyl
Prior art date
Application number
PCT/GB2004/003705
Other languages
English (en)
Inventor
Fleur Radford
Rosemary Lynch
Sarah Louise Mellor
Christopher John Hobbs
Jenny Christine Gilbert
Stephen Stokes
Angela Glen
Andrea Fiumana
Nichola Jane Smith
Christopher Geoffrey Earnshaw
Lars Jacob Stray Knutsen
Original Assignee
Ionix Pharmaceuticals Limited
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Priority claimed from GB0320294A external-priority patent/GB0320294D0/en
Priority claimed from GB0330044A external-priority patent/GB0330044D0/en
Application filed by Ionix Pharmaceuticals Limited filed Critical Ionix Pharmaceuticals Limited
Priority to EP04768255A priority Critical patent/EP1664010A1/fr
Publication of WO2005068448A1 publication Critical patent/WO2005068448A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/92—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with a hetero atom directly attached to the ring nitrogen atom
    • C07D211/96—Sulfur atom
    • 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]
    • 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
    • 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
    • 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
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur 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
    • 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
    • C07D413/04—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 directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond

Definitions

  • the present invention relates to specific sulphonylpiperidine derivatives which act as inhibitors of N-type calcium channels.
  • Mammalian ion channels are becoming increasingly well characterised, and this is especially true of calcium channels.
  • Voltage-gated calcium channels are critical components for the functioning of the nervous system, and they signal a painful event.
  • 7 subtypes of these channels have been identified (L, N, T, O, P, Q and R), each expressed in various combinations by neuronal and non- neuronal cells (Perez-Reyes, E.; Schneider, T. DrugDev. Res., 1994, 33, 295-318). These channels are now recognised as valid targets for pain therapeutics and as neuroprotective agents (Cox, B.; Denyer, J.C.
  • R 3 , R 4 and R 5 are the same or different and are selected from hydrogen, halogen, hydroxy, thio, amino, cyano, nitro, -C ⁇ alkyl, C -C 6 alkenyl, C -C 6 alkynyl, Ci-C 6 alkoxy, -C ⁇ alkylthio, mono(C 1 -C 6 alkyl)amino and di(C 1 -C 6 alkyl)amino; and n is from 0 to 4, the alkyl, alkenyl and alkynyl groups and moieties in R 1 to R 5 being unsubstituted or substituted by one, two or three substituents which are
  • a C 2 -C 6 alkenyl group is a linear or branched C 2 -C 6 alkylene group.
  • an alkenyl group or moiety is saturated except for one double bond.
  • it is an ethenyl, propenyl or butenyl group.
  • it is an ethenyl group.
  • a divalent alkenyl group can be attached via the same carbon atom, via adjacent carbon atoms or via non-adjacent carbon atoms.
  • a C 2 -C 6 alkynyl group is a linear or branched C 2 -C 6 alkynyl group.
  • a C C 6 haloalkyl group is typically a said -C ⁇ alkyl group, substituted by one or more said halogen atoms. Typically, it is substituted by 1, 2 or 3 said halogen atoms.
  • haloalkyl groups include perhaloalkyl groups such as -CX 3 wherein X is a said halogen atom.
  • Preferred haloalkyl groups are fluoroalkyl groups such as -CF 3 , -CHF 2 and -CH 2 F.
  • a Ci-C 6 haloalkoxy group is typically a said -C ⁇ alkoxy group substituted by one or more said halogen atoms.
  • a 5- to 10-membered heterocyclyl group or moiety is a monocyclic group or moiety or a bicyclic fused group or moiety.
  • Preferred bicyclic fused groups and moieties are 5- to 10-membered moieties in which a 5- to 6- membered ring is fused to a phenyl ring, to form a 9- to 10-membered heterocyclic group.
  • suitable such 5- to 6-membered heterocyclic groups are pyrrolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, piperidinyl, tetrahydropyranyl and tetrahydrothiopyranyl.
  • substituents on an aryl, heteroaryl, carbocyclyl or heterocyclyl group or moiety is a -(C 1 -C 4 alkyl)-O-(C 1 -C 4 alkyl), -(d-C 4 alkyl)-S-(C 1 -C 4 alkyl), -(C 1 -C 4 alkyl)-NR'-(C 1 -C 4 alkyl), -CO-(C ! -C 4 alkyl), -CO-O-(C 1 -C 4 alkyl)or -CONRHQ- alkyl) substituent.
  • R 3 , R 4 and R 5 are the same or different and are selected from hydrogen, fluorine, chlorine, bromine, cyano, C 1 -C 4 alkyl, C 2 -C 4 alkenyl, C 1 -C 2 alkoxy, -C2 alkylthio, mono(C 1 -C 2 alkyl)amino and di(C ⁇ -C 2 alkyl)amino. More preferably, R 3 , R 4 and R 5 are the same or different and are selected from hydrogen, fluorine, chlorine, bromine, cyano, -C 4 alkyl, C 1 -C 2 alkoxy or ethenyl.
  • the aryl, heteroaryl, carbocyclyl and heterocyclyl groups and moieties in R 1 and R 6 are unsubstituted or substituted by one, two or three unsubstituted substituents which are the same or different and are selected from fluorine, chlorine, bromine, hydroxy, amino, thio, C 1 -C 4 alkyl, -C 4 alkoxy, -C 4 alkylthio, mono(Ci-C 4 alkyl)amino, di(C C 4 alkyl)amino, C 1 -C 4 haloalkyl, -C 4 haloalkoxy or -C 4 haloalkylthio substituents.
  • provisos (a) and (b)(i) apply.
  • R 1 , R 3 , R 4 , R 5 and R 6 are as defined for formula (II), provided that R 1 is not -CO-O-CH 2 -CH 3 or -CO-O-CH(CH 3 ) 2 and when the phenyl ring substituted by R 3 , R 4 and R 5 is a para-fluorophenyl group, then R 1 is not a 5-membered heteroaryl group.
  • R 1 , R 3 , R 4 , R 5 and R 6 are as defined for formula (II), provided that: (a) when the phenyl ring substituted by R 3 , R 4 and R 5 is a para-fluorophenyl group, then R 1 is not a 5-membered heteroaryl group; or
  • Chronic pain is sometimes a result of persistent dysfunction of the nociceptive pain system.
  • Examples of chronic pains which can be alleviated with the compounds of the invention include trigeminal neuralgia, post-herpetic neuralgia (a form of chronic pain accompanied by skin changes in a dermatomal distribution following damage by acute Herpes Zoster disease), diabetic neuropathy, causalgia, "phantom limb" pain, pain associated with osteoarthritis, pain associated with rheumatoid arthritis, pain associated with cancer, pain associated with HIN, neuropathic pain, migraine and other conditions associated with chronic cephalic pain, primary and secondary hyperalgesia, inflammatory pain, nociceptive pain, tabes dorsalis, spinal cord injury pain, central pain, post-herpetic pain, noncardiac chest pain, irritable bowel syndrome and pain associated with bowel disorders and dyspepsia.
  • the compounds of the invention can be utilised in the treatment of tinnitus, itch such as pruritoceptive, neuropathic, neurogenic and psychogenic itch, as well as urinary tract disorders such as urinary incontinence, and irritable bowel syndrome.
  • the compounds of the invention may also have application in disorders which are generally associated with blocking of L-type calcium channels, such as cardiovascular, antiasthmatic and antibronchoconstriction disorders for example in the prevention and treatment of disorders such as hypersensitivity, allergy, asthma, bronchospasm, dysmenorrhea, esophageal spasm, premature labour, gastrointestinal motility disorders and cardiovascular disorders wherein the cardiovascular disorder is selected from the group consisting of hypertension, myocardial ischemia, angina, congestive heart failure, myocardial infarction and stroke.
  • the compounds of the invention can be utilised in the treatment of hypersensitivity disorders such as urinary tract disorders.
  • Step 2 A mixture of (2S)-ethyl- 1 -(4-trifluoromethylbenzenesulphonyl)piperidine-2- carboxylate (0.638g, 1.75mmol) and lithium hydroxide monohydrate (0.011 g, 1.83mmol) in ethanol (8mL) and water (2mL) was stirred at room temperature for 3 Oh. The solvent was removed in vacuo and the residue dissolved in water. The aqueous layer was acidified and extracted with dichloromethane. The organic layer was washed with brine and dried over MgSO 4 .
  • Step 3 Using an analogous method to that described for Example 1, Step 3 starting from 1 -(4-trifluoromethylbenzenesulphonyl)piperidine-2-carboxylic acid (0.135g, 0.4mmol) and triturating the residue with isohexane gave the title compound as a colourless solid (0.073g, 46%). HPLC (Method A) retention time 4.60min. Mass spectrum (ES+) m/z 338 (M-'Bu+H).
  • Step 2 Using an analogous method to that described for Example 2, Step 2 starting from (2S)-ethyl-l-(2-chloro-4-trifluoromethylbenzenesulphonyl)piperidine-2-carboxylate gave (2S)- 1 -(2-Chloro-4-trifluoromethylbenzenesulphonyl)piperidine-2-carboxylic acid as a colourless oil (0.097g, 89%). HPLC (Method B) retention time 2.53min. Mass spectrum (ES-) m/z 370 (M-H).
  • Step ! Using an analogous method to that described for Example 2, Step 2 starting from (3i?)-ethyl-l-(2-bromo-4-trifluoromethylbenzenesulphonyl)piperidine-3-carboxylate gave (3i-)-l-(2-Bromo-4-trifluoromethylbenzenesulphonyl)piperidine-3-carboxylic acid as a pale yellow solid (0.985g, 82%). HPLC (Method B) retention time 2.51min. Mass spectrum (ES-) m/z AIAIAX6 (M-H).

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne des composés de formule générale (I), leurs tautomères et leurs sels pharmaceutiquement acceptables, qui présente une action antagoniste de canaux calcium de type N. Lesdits composés s'utilisent dans le traitement ou la prévention d'un état induit par canaux calcium de type N, comme la douleur.
PCT/GB2004/003705 2003-08-29 2004-08-31 Sulfonamides a action antagoniste sur des canaux calcium de type n WO2005068448A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP04768255A EP1664010A1 (fr) 2003-08-29 2004-08-31 Antagoniste des canaux calcium type n, de type sulfonamides

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GB0320294A GB0320294D0 (en) 2003-08-29 2003-08-29 Chemical compounds
GB0320294.2 2003-08-29
GB0330044A GB0330044D0 (en) 2003-12-24 2003-12-24 Chemical compounds
GB0330044.9 2003-12-24

Publications (1)

Publication Number Publication Date
WO2005068448A1 true WO2005068448A1 (fr) 2005-07-28

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EP (1) EP1664010A1 (fr)
WO (1) WO2005068448A1 (fr)

Cited By (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005113542A2 (fr) * 2004-05-20 2005-12-01 Elan Pharmaceuticals, Inc. Inhibiteurs sulfonamido n-cycliques de gamma-secretase
WO2006030211A2 (fr) * 2004-09-14 2006-03-23 Vernalis (R & D) Limited Sulfamides acycliques
WO2007125398A2 (fr) * 2006-04-27 2007-11-08 Pfizer Japan Inc. Sulfonamides
JP2010504930A (ja) * 2006-09-29 2010-02-18 グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング 置換されたスルホンアミド誘導体
WO2010084050A2 (fr) 2009-01-13 2010-07-29 Novartis Ag Dérivés de quinazolinone utiles comme antagonistes vanilloïdes
WO2010091721A1 (fr) * 2009-02-11 2010-08-19 Glaxo Group Limited Dérivés de 1-arylsulfonylpipéridine substitués en position 3 destinés au traitement de la douleur
JP2010529020A (ja) * 2007-05-31 2010-08-26 塩野義製薬株式会社 オキシイミノ化合物およびその使用
WO2010096371A3 (fr) * 2009-02-18 2010-11-11 Boehringer Ingelheim International Gmbh Composés hétérocycliques qui modulent le récepteur cb2
EP2305652A2 (fr) 2005-12-08 2011-04-06 Novartis AG Dérivés de quinazolinone trisubstituée en tant qu'agonistes de vanilloïde
WO2011092290A1 (fr) 2010-02-01 2011-08-04 Novartis Ag Dérivés de pyrazolo[5,1-b] utilisés en tant qu'antagonistes du récepteur de crf-1
WO2011092293A2 (fr) 2010-02-01 2011-08-04 Novartis Ag Dérivés de cyclohexylamide utilisés en tant qu'antagonistes du récepteur du crf
WO2011095450A1 (fr) 2010-02-02 2011-08-11 Novartis Ag Dérivés de cyclohexylamide à titre d'antagonistes du récepteur crf
EP2477963A1 (fr) * 2009-09-18 2012-07-25 Zalicus Pharmaceuticals Ltd. Dérivés d'aryl sulfones comme bloqueurs des canaux calciques
US8324249B2 (en) 2008-08-01 2012-12-04 Purdue Pharma L.P. Tetrahydropyridinyl and dihydropyrrolyl compounds and the use thereof
WO2012164473A1 (fr) 2011-05-27 2012-12-06 Novartis Ag Dérivés de pipéridine 3-spirocyclique comme agonistes du récepteur de la ghréline
WO2013164790A1 (fr) 2012-05-03 2013-11-07 Novartis Ag Sel de l-malate de dérivés de 2,7-diaza-spiro[4.5]déc-7-yle et ses formes cristallines à titre d'agonistes des récepteurs de ghreline
US8846936B2 (en) 2010-07-22 2014-09-30 Boehringer Ingelheim International Gmbh Sulfonyl compounds which modulate the CB2 receptor
US8865744B1 (en) 2013-05-17 2014-10-21 Boehringer Ingelheim International Gmbh (Cyano-dimethyl-methyl)-isoxazoles and -[1,3,4]thiadiazoles
US9315454B2 (en) 2010-01-15 2016-04-19 Boehringer Ingelheim International Gmbh Compounds which modulate the CB2 receptor
CN105732458A (zh) * 2014-12-29 2016-07-06 成都先导药物开发有限公司 吡咯酰胺类化合物及其制备方法与用途
CN105732459A (zh) * 2014-12-29 2016-07-06 成都先导药物开发有限公司 吡咯酰胺类化合物及其制备方法与用途
WO2016107227A1 (fr) * 2014-12-29 2016-07-07 成都先导药物开发有限公司 Composé pyrrole-amide, procédé de préparation de ce dernier, et son utilisation

Citations (1)

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WO2002080928A1 (fr) * 2001-04-03 2002-10-17 Merck & Co., Inc. Antagonistes de nmda/nr2b nonaryl-heterocyclo amidyle n-substitues

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Publication number Priority date Publication date Assignee Title
WO2002080928A1 (fr) * 2001-04-03 2002-10-17 Merck & Co., Inc. Antagonistes de nmda/nr2b nonaryl-heterocyclo amidyle n-substitues

Non-Patent Citations (1)

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KOEHLER, J. J. ET AL: "Intramolecular radical reactions in .alpha.-halomethyl substituted piperidine sulfonamides", TETRAHEDRON LETTERS , (7), 631-4 CODEN: TELEAY; ISSN: 0040-4039, 1977, XP002311574 *

Cited By (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005113542A3 (fr) * 2004-05-20 2006-03-02 Elan Pharm Inc Inhibiteurs sulfonamido n-cycliques de gamma-secretase
WO2005113542A2 (fr) * 2004-05-20 2005-12-01 Elan Pharmaceuticals, Inc. Inhibiteurs sulfonamido n-cycliques de gamma-secretase
WO2006030211A2 (fr) * 2004-09-14 2006-03-23 Vernalis (R & D) Limited Sulfamides acycliques
WO2006030211A3 (fr) * 2004-09-14 2006-06-01 Vernalis R&D Ltd Sulfamides acycliques
EP2305652A2 (fr) 2005-12-08 2011-04-06 Novartis AG Dérivés de quinazolinone trisubstituée en tant qu'agonistes de vanilloïde
WO2007125398A2 (fr) * 2006-04-27 2007-11-08 Pfizer Japan Inc. Sulfonamides
WO2007125398A3 (fr) * 2006-04-27 2008-03-06 Pfizer Japan Inc Sulfonamides
JP2010504930A (ja) * 2006-09-29 2010-02-18 グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング 置換されたスルホンアミド誘導体
JP2010529020A (ja) * 2007-05-31 2010-08-26 塩野義製薬株式会社 オキシイミノ化合物およびその使用
US8324249B2 (en) 2008-08-01 2012-12-04 Purdue Pharma L.P. Tetrahydropyridinyl and dihydropyrrolyl compounds and the use thereof
WO2010084050A2 (fr) 2009-01-13 2010-07-29 Novartis Ag Dérivés de quinazolinone utiles comme antagonistes vanilloïdes
WO2010091721A1 (fr) * 2009-02-11 2010-08-19 Glaxo Group Limited Dérivés de 1-arylsulfonylpipéridine substitués en position 3 destinés au traitement de la douleur
JP2012518038A (ja) * 2009-02-18 2012-08-09 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング Ｃｂ２受容体を変調する複素環化合物
US8889670B2 (en) 2009-02-18 2014-11-18 Boehringer Ingelheim International Gmbh Heterocyclic compounds which modulate the CB2 receptor
WO2010096371A3 (fr) * 2009-02-18 2010-11-11 Boehringer Ingelheim International Gmbh Composés hétérocycliques qui modulent le récepteur cb2
CN102762534A (zh) * 2009-09-18 2012-10-31 扎里卡斯药品有限公司 作为钙通道阻断剂的芳基砜衍生物
EP2477963A1 (fr) * 2009-09-18 2012-07-25 Zalicus Pharmaceuticals Ltd. Dérivés d'aryl sulfones comme bloqueurs des canaux calciques
EP2477963A4 (fr) * 2009-09-18 2013-02-27 Zalicus Pharmaceuticals Ltd Dérivés d'aryl sulfones comme bloqueurs des canaux calciques
US9315454B2 (en) 2010-01-15 2016-04-19 Boehringer Ingelheim International Gmbh Compounds which modulate the CB2 receptor
WO2011092290A1 (fr) 2010-02-01 2011-08-04 Novartis Ag Dérivés de pyrazolo[5,1-b] utilisés en tant qu'antagonistes du récepteur de crf-1
WO2011092293A2 (fr) 2010-02-01 2011-08-04 Novartis Ag Dérivés de cyclohexylamide utilisés en tant qu'antagonistes du récepteur du crf
WO2011095450A1 (fr) 2010-02-02 2011-08-11 Novartis Ag Dérivés de cyclohexylamide à titre d'antagonistes du récepteur crf
US8846936B2 (en) 2010-07-22 2014-09-30 Boehringer Ingelheim International Gmbh Sulfonyl compounds which modulate the CB2 receptor
WO2012164473A1 (fr) 2011-05-27 2012-12-06 Novartis Ag Dérivés de pipéridine 3-spirocyclique comme agonistes du récepteur de la ghréline
WO2013164790A1 (fr) 2012-05-03 2013-11-07 Novartis Ag Sel de l-malate de dérivés de 2,7-diaza-spiro[4.5]déc-7-yle et ses formes cristallines à titre d'agonistes des récepteurs de ghreline
US8865744B1 (en) 2013-05-17 2014-10-21 Boehringer Ingelheim International Gmbh (Cyano-dimethyl-methyl)-isoxazoles and -[1,3,4]thiadiazoles
US10112934B2 (en) 2013-05-17 2018-10-30 Centrexion Therapeutics Corporation (Cyano-dimethyl-methyl)-isoxazoles and -[1,3,4]thiadiazoles
US11725004B2 (en) 2013-05-17 2023-08-15 Centrexion Therapeutics Corporation (Cyano-dimethyl-methyl)-isoxazoles and -[1,3,4]thiadiazoles
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US9650370B2 (en) 2013-05-17 2017-05-16 Centrexion Therapeutics Corporation (Cyano-dimethyl-methyl)-isoxazoles and -[1,3,4]thiadiazoles
CN105732458A (zh) * 2014-12-29 2016-07-06 成都先导药物开发有限公司 吡咯酰胺类化合物及其制备方法与用途
JP2018503683A (ja) * 2014-12-29 2018-02-08 成都先導薬物開発有限公司 ピロールアミド系化合物、その製造方法、及び用途
US10266489B2 (en) 2014-12-29 2019-04-23 Hitgen Ltd Pyrrolic amide compound and preparation method and application thereof
CN105801464B (zh) * 2014-12-29 2019-05-28 成都先导药物开发有限公司 吡咯酰胺类化合物及其制备方法与用途
CN105732459B (zh) * 2014-12-29 2019-05-31 成都先导药物开发有限公司 吡咯酰胺类化合物及其制备方法与用途
CN105801464A (zh) * 2014-12-29 2016-07-27 成都先导药物开发有限公司 吡咯酰胺类化合物及其制备方法与用途
WO2016107227A1 (fr) * 2014-12-29 2016-07-07 成都先导药物开发有限公司 Composé pyrrole-amide, procédé de préparation de ce dernier, et son utilisation
CN105732459A (zh) * 2014-12-29 2016-07-06 成都先导药物开发有限公司 吡咯酰胺类化合物及其制备方法与用途

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