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1. WO2006061642 - COMPOUNDS

Publication Number WO/2006/061642
Publication Date 15.06.2006
International Application No. PCT/GB2005/004753
International Filing Date 09.12.2005
IPC
C07D 495/04 2006.1
CCHEMISTRY; METALLURGY
07ORGANIC CHEMISTRY
DHETEROCYCLIC COMPOUNDS
495Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
02in which the condensed system contains two hetero rings
04Ortho-condensed systems
A61K 31/435 2006.1
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31Medicinal preparations containing organic active ingredients
33Heterocyclic compounds
395having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
435having six-membered rings with one nitrogen as the only ring hetero atom
A61P 29/00 2006.1
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
29Non-central analgesic, antipyretic or antiinflammatory agents, e.g antirheumatic agents; Non-steroidal antiinflammatory drugs (NSAIDs)
A61P 37/00 2006.1
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
37Drugs for immunological or allergic disorders
CPC
A61P 1/04
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
1Drugs for disorders of the alimentary tract or the digestive system
04for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
A61P 25/00
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
25Drugs for disorders of the nervous system
A61P 29/00
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
29Non-central analgesic, antipyretic or anti-inflammatory agents, e.g antirheumatic agents; Non-steroidal anti-inflammatory drugs (NSAIDs)
A61P 3/10
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
3Drugs for disorders of the metabolism
08for glucose homeostasis
10for hyperglycaemia, e.g. antidiabetics
A61P 37/00
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
37Drugs for immunological or allergic disorders
A61P 37/06
AHUMAN NECESSITIES
61MEDICAL OR VETERINARY SCIENCE; HYGIENE
PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
37Drugs for immunological or allergic disorders
02Immunomodulators
06Immunosuppressants, e.g. drugs for graft rejection
Applicants
  • XENTION DISCOVERY LIMITED [GB]/[GB] (AllExceptUS)
  • FORD, John [GB]/[GB] (UsOnly)
  • MADGE, David, John [GB]/[GB] (UsOnly)
  • PALMER, Nicholas, John [GB]/[GB] (UsOnly)
  • ATHERALL, John, Frederick [GB]/[GB] (UsOnly)
  • JOHN, Derek [GB]/[GB] (UsOnly)
Inventors
  • FORD, John
  • MADGE, David, John
  • PALMER, Nicholas, John
  • ATHERALL, John, Frederick
  • JOHN, Derek
Agents
  • CHAPMAN, Paul, William
Priority Data
0427005.409.12.2004GB
60/634,27109.12.2004US
Publication Language English (en)
Filing Language English (EN)
Designated States
Title
(EN) COMPOUNDS
(FR) COMPOSES
Abstract
(EN) The invention provides compounds of the formula: (I) wherein R1 is aryl, heteroaryl, cycloalkyl or alkyl; R2 is H, alkyl, nitro, CO2R7, CONR5R6 or halo; R3 and R4 are H, NR5R6, NC(O)R7, halo, trifluromethyl, alkyl, CONR5R6, CO2R7, nitrile or alkoxy; R5 and R6 may be the same or different and may be H, alkyl, aryl, heteroaryl or cycloalkyl; or R5 and R6 may together form a saturated, unsaturated or partially saturated 4 to 7 member ring, wherein said ring may optionally comprise one or more further heteroatoms selected from N, O or S; R7 is H or alkyl; A is H, halo, or a group of formula X-L-Y; X is O,S or NR8; R8 is H or alkyl; L is (CH2)n, where n is 0, 1, 2, 3 or 4; and Y is aryl, a heterocyclic group, alkyl, alkenyl or cycloalkyl; the products of mono- and di-oxidation of sulphur and/or mono-oxidation of nitrogen moieties in compounds of formula (I); or a pharmaceutically acceptable salt thereof. These compounds find use as inhibitors of potassium ion channels and thus are useful in the treatment of various conditions including arrhythmia and type-2 diabetes mellitus.
(FR) La présente invention concerne des composés de formule : (I) dans laquelle R1 est un groupe aryle, hétéroaryle, cycloalkyle ou alkyle ; R2 est un atome d’hydrogène, un groupe alkyle, nitro, CO2R7, CONR5R6 ou un halogéno ; R3 et R4 représentent un atome d'hydrogène, NR5R6, NC(O)R7, un groupe halogéno, triflurométhyle, alkyle, CONR5R6, CO2R7, nitrile ou alcoxy ; R5 et R6 peuvent être identiques ou différents et être un atome d’hydrogène, un groupe alkyle, aryle, hétéroaryle ou cycloalkyle ; ou bien R5 et R6 peuvent former ensemble un cycle ayant de 4 à 7 chaînons saturé, insaturé ou partiellement saturé, ledit cycle pouvant éventuellement comprendre un ou plusieurs autres hétéroatomes sélectionnés parmi N, O ou S ; R7 est un atome d’hydrogène ou un groupe alkyle ; A est un atome d’hydrogène, un groupe halogéno, ou un groupe de formule X-L-Y ; X représente un atome d’oxygène ou de soufre ou NR8 ; R8 représente un atome d’hydrogène ou un groupe alkyle ; L est (CH2)n, n valant 0, 1, 2, 3 ou 4 ; et Y représente un groupe aryle, hétérocyclique, alkyle, alcényle ou cycloalkyle. L’invention concerne également les produits de la mono- et de la di-oxydation du soufre et/ou de la mono-oxydation des groupements fonctionnels de l’azote dans les composés de formule (I) ; ou un sel pharmaceutiquement acceptable de ces composés. Ces composés trouvent une utilisation en tant qu’inhibiteurs des canaux ioniques du potassium et ainsi sont utiles dans le traitement de diverses pathologies dont l’arythmie et le diabète de type-2.
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