Hydroxyeicosatetraenoic acid analogs, the composition thereof and use thereof in the manufacture of a medicament for treating dry eye and other disorders requiring the wetting of the eye in mammals

• Main Authors: HELLBERG, MARK R, KLIMKO, PETER G, FALCK, JOHN R, CONROW, RAYMOND E
• Format: Patent
• Language: English
• Published: 21.05.2007
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; 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

Hydroxyeicosatetraenoic acid analogs and methods of their use in treating dry eye disorders are disclosed. A pharmaceutical composition for the treatment of dry eye and other disorders requiring the wetting of the eye comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of one or more compounds of the following formula I, wherein: R1 is CO2R, CONR2R3, CH2OR4, CH2NR5R6, CH2N3, CH2Hal, CH2NO2, CH2SR20, COSR21, or 2,3,4,5-tetrazol-1-yl, where: R is H, C1-6 alkyl, C3-8 cycloalkyl, phenyl, benzyl, or CO2R forms a salt of the form CO2-M+, where M+ is Li+, Na+, Na+, or NH4+; R2 and R3 are the same or different and are H, C1-6 alkyl, C3-8 cycloalkyl, phenyl, or benzyl; R5 and R6 are the same or different and are H, C1-6 alkyl, C3-8 cycloalkyl, phenyl, or benzyl, or are C(O)R22, where R22 is H, C1-6 alkyl, C3-8 cycloalkyl, phenyl, or benzyl; R4 is H, C1-6 alkyl, C3-8 cycloalkyl, phenyl, or benzyl, or are C(O)R22, where R22 is H, C1-6 alkyl, C3-8 cycloalkyl, phenyl, or benzyl; Hal is F, Cl, Br, or I; R20 is H, alkyl or acyl; R21 is H, C1-6 alkyl, C3-8 cycloalkyl, phenyl, or benzyl; K is CH2CH2, CH=CH, or C=C; B and D are the same or different and are CH2CH2, CH=CH, or C=C; and Y is C(O) (i.e. a carbonyl group) or Y is formula, wherein R9 is H, C1-6 alkyl, C3-8 cycloalkyl, phenyl, or benzyl; or is C(O)R22, where R22 is H, C1-6 alkyl, C3-8 cycloalkyl, phenyl, or benzyl.