Novel processes for the preparation of a compound of Formula I-2 substantially free of the 5,6-trans isomer: ##STR00001##
wherein ##STR00002##
R.sub.2, R.sub.3 and R.sub.4 are as defined in the specification are provided. Novel intermediates for the preparations of isomer free Prostaglandins and derivatives thereof are also provided.

Novel processes for the preparation of a compound of Formula I-2 substantially free of the 5,6-trans isomer: ##STR00001##
wherein ##STR00002##
R.sub.2, R.sub.3 and R.sub.4 are as defined in the specification are provided. Novel intermediates for the preparations of isomer free Prostaglandins and derivatives thereof are also provided.

The present invention relates to crystalline 1-adamantanamine salts, and polymorphic forms thereof, of prostaglandin analog intermediates of formula 3a, 4a and 6a, useful in the preparation of Tafluprost and Lubiprostone and processes for their preparation. The process includes combining 1-adamantanamine, water, an organic solvent, and a compound of Formula 3 or 6, thereby obtaining a suspension. The process also includes isolating the solid salt of Formula 3a or 6a from the suspension.

The present invention relates to crystalline 1-adamantanamine salts, and polymorphic forms thereof, of prostaglandin analog intermediates of formula 3a, 4a and 6a, useful in the preparation of Tafluprost and Lubiprostone and processes for their preparation. The process includes combining 1-adamantanamine, water, an organic solvent, and a compound of Formula 3 or 6, thereby obtaining a suspension. The process also includes isolating the solid salt of Formula 3a or 6a from the suspension.

The subject of the invention is process for the preparation of the prostaglandin amides of the general formula I, ##STR00001## where in the formula the bonds marked with dotted lines may be single or double bonds, in the case of double bounds at positions 5,6 and 13,14 they may be in cis or in trans orientation, Q stands for a hydroxyl-group and Z stands for a hydroxyl- or oxo-group, R.sup.1 and R.sup.2 independently represent hydrogen atom or a straight or branched C.sub.1-10 alkyl- or aralkyl-group, optionally substituted with ONO.sub.2 group, or an aralkyl- or aryl-group, which contains heteroatom, R.sup.3 represents a straight or branched, saturated or unsaturated C.sub.4-6 hydrocarbon group, or a C.sub.4-10 alkylcycloalkyl- or cycloalkyl-group, or an optionally with alkyl group or halogen atom substituted phenyl-, C.sub.7-10 alkylaryl- or hetaryl-group, Y represents (CH.sub.2).sub.n group or O atom or S atom, and where n=0-3.

The subject of the invention is process for the preparation of the prostaglandin amides of the general formula I, ##STR00001## where in the formula the bonds marked with dotted lines may be single or double bonds, in the case of double bounds at positions 5,6 and 13,14 they may be in cis or in trans orientation, Q stands for a hydroxyl-group and Z stands for a hydroxyl- or oxo-group, R.sup.1 and R.sup.2 independently represent hydrogen atom or a straight or branched C.sub.1-10 alkyl- or aralkyl-group, optionally substituted with ONO.sub.2 group, or an aralkyl- or aryl-group, which contains heteroatom, R.sup.3 represents a straight or branched, saturated or unsaturated C.sub.4-6 hydrocarbon group, or a C.sub.4-10 alkylcycloalkyl- or cycloalkyl-group, or an optionally with alkyl group or halogen atom substituted phenyl-, C.sub.7-10 alkylaryl- or hetaryl-group, Y represents (CH.sub.2).sub.n group or O atom or S atom, and where n=0-3.

Novel processes for the preparation of a compound of Formula I-2 substantially free of the 5,6-trans isomer: ##STR00001##
wherein ##STR00002##
R.sub.2, R.sub.3 and R.sub.4 are as defined in the specification are provided. Novel intermediates for the preparations of isomer free Prostaglandins and derivatives thereof are also provided.

Novel processes for the preparation of a compound of Formula I-2 substantially free of the 5,6-trans isomer: ##STR00001##
wherein ##STR00002##
R.sub.2, R.sub.3 and R.sub.4 are as defined in the specification are provided. Novel intermediates for the preparations of isomer free Prostaglandins and derivatives thereof are also provided.

Disclosed herein are compounds having formula (I) wherein a dashed line represents the presence or adsence of a bond; Y is an organic acid functional group, or an amide or ester thereof; or Y is hydroxymethyl or an ester thereof; or Y is a tetrazolyl functional group; A is (CH.sub.2).sub.6, cis CH.sub.2CHCH(CH.sub.2).sub.3, or CH.sub.2CC(CH.sub.2).sub.3, wherein 1 or 2 carbon atoms may be replaced by S or O; or A is (CH.sub.2).sub.mAr(CH.sub.2).sub.o, wherein Ar is interarylene or heterointerarylene, the sum of m and o is 1, 2, 3, or 4, and wherein 1 CH.sub.2 may be replaced by S or O, and 1 CH.sub.2CH.sub.2 may be replaced by CHCH or CC; U.sup.1 and U.sup.2 are independently selected from H, O, OH, F, Cl, and CN; and B is aryl or heteroaryl, for use as acular hypotensive agent.

Disclosed herein are compositions comprising an amide related to a prostaglandin and a biogenic amine. Other aspects relate to certain chemical compounds, pharmaceutical compositions, and methods of treating glaucoma.