Nicotinamide derivatives and their use as medicaments

• Main Authors: SATOSHI NAGATO, AKIHARU KAJIWARA, JAMES MARTIN STADDON, JOANNA ELIZABETH BRASHAW, LEE LAURENCE RUBIN, MARY LOUISE MORGAN
• Format: Patent
• Language: English
• Published: 24.04.2002
• Edition: 7
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

A nicotinic acid amide derivative of formula (I), pharmacologically acceptable salts and pharmaceutical compositions thereof: wherein R 1 is H or lower alkyl; R 2 is optionally substituted pyridinyl, pyridinemethyl, N-benzylpiperidinyl, isoquinolyl or benzyl; R 3 is optionally substituted cyclopentyl, cyclohexyl, cyclooctyl, norbornyl, adamantyl, piperidyl, pyridyl, isoquinolyl or azabicyclooctyl wherein the ring system is attached to the nicotinamide ring by means of an oxygen or NH group and R 4 is H or lower alkoxy. The compounds are useful for the prevention and treatment of stroke, brain edema after stroke and a variety of allergic and inflammatory diseases, e.g. asthma, chronic bronchitis, shock, rheumatoid arthritis, reperfusion injury, encephalomyelitis and multiple sclerosis. The compounds are prepared from intermediates wherein R 3 is chlorine which in turn are prepared from reaction of the corresponding acid with HNR 1 R 2 .