It is provided a process for the preparation of bimatoprost, which comprises: a) reacting a compound of formula (III) with ethylamine in the presence of a suitable solvent; and b) deprotecting compound obtained in step a) to obtain bimatoprost, wherein R.sup.1 is selected from (C.sub.1-C.sub.16)alkyl, (C.sub.1C.sub.16)haloalkyl, (C.sub.2-C.sub.16)alkenyl, (C.sub.2-C.sub.16)haloalkenyl, (C.sub.1-C.sub.16)alkoxy(C.sub.1-C.sub.16)alkyl, aryl, (C.sub.1-C.sub.16)alkylaryl, allyl, (CH.sub.2CH.sub.2O).sub.nCH.sub.3 wherein n=1, 2, 3 or 4, and CH(OCH.sub.2CH.sub.2).sub.2; R.sub.2 is selected from H, (C.sub.1-C.sub.16)alkyl, (C.sub.1-C.sub.16)haloalkyl, (C.sub.2-C.sub.16)alkenyl, (C.sub.2-C.sub.16)haloalkenyl, (C.sub.1-C.sub.16)alkoxy(CrC.sub.16)alkyl, aryl, (C.sub.1-C.sub.16)alkylaryl, allyl; or, alternatively, R.sup.1 and R.sup.2 taken together are selected from CH.sub.2CH.sub.2CH.sub.2, CH.sub.2CH.sub.2, OCH.sub.2CH.sub.2, and OCHCH. There are also provided intermediates useful in such preparation process. ##STR00001##

Co-crystals comprising the Nuclear receptor related 1 protein-ligand binding domain (Nurr1-LBD) and a cyclopentenone prostaglandin are provided. Also provided are methods of identifying or designing Nurr1-modulating ligands and compounds based on the crystal structures described herein as well as the applications of said ligands and compounds as Nurr1 modulators or medicaments.

It is provided a process for the preparation of bimatoprost, which comprises: a) reacting a compound of formula (III) with ethylamine in the presence of a suitable solvent; and b) deprotecting compound obtained in step a) to obtain bimatoprost, wherein R.sup.1 is selected from (C.sub.1-C.sub.16)alkyl, (C.sub.1C.sub.16)haloalkyl, (C.sub.2-C.sub.16)alkenyl, (C.sub.2-C.sub.16)haloalkenyl, (C.sub.1-C.sub.16)alkoxy(C.sub.1-C.sub.16)alkyl, aryl, (C.sub.1-C.sub.16)alkylaryl, allyl, (CH.sub.2CH.sub.2O).sub.nCH.sub.3 wherein n=1, 2, 3 or 4, and CH(OCH.sub.2CH.sub.2).sub.2; R.sub.2 is selected from H, (C.sub.1-C.sub.16)alkyl, (C.sub.1-C.sub.16)haloalkyl, (C.sub.2-C.sub.16)alkenyl, (C.sub.2-C.sub.16)haloalkenyl, (C.sub.1-C.sub.16)alkoxy(CrC.sub.16)alkyl, aryl, (C.sub.1-C.sub.16)alkylaryl, allyl; or, alternatively, R.sup.1 and R.sup.2 taken together are selected from CH.sub.2CH.sub.2CH.sub.2, CH.sub.2CH.sub.2, OCH.sub.2CH.sub.2, and OCHCH. There are also provided intermediates useful in such preparation process.

##STR00001##

The present invention relates to a novel prostaglandin derivative having an alkynyl group on -chain, particularly, a novel prostaglandin derivative having a double bond at the 2-position and an alkynyl group on the -chain and a medicament containing the compound as an active ingredient. According to the present invention, a compound represented by the formula (1) or a pharmaceutically acceptable salt thereof; ##STR00001## wherein each symbol is as defined in the present specification, or a cyclodextrin clathrate compound thereof, and a medicament containing the compound as an active ingredient, particularly, a medicament for the prophylaxis or treatment of a blood flow disorder associated with spinal canal stenosis or chronic arterial occlusion, can be provided.

The present invention relates to a process for preparing hexanoic acid, 6-(nitrooxy)-, (1S,2E)-3-[(1R,2R,3S,5R)-2-[(2Z)-7-(ethylamino)-7-oxo-2-hepten-1-yl]-3,5-dihydroxycyclopentyl]-1-(2-phenylethyl)-2-propen-1-yl ester of formula (I).

##STR00001##

In accordance with the present invention, the compound (I) can be efficiently prepared with high purity by coupling bimatoprost in a boronate protected form with 6-(nitrooxy)hexanoyl chloride and removing the boronate protecting group.

The invention also relates to a process for the preparation of 6-(nitrooxy) hexanoic acid having a HPLC purity equal to or greater than 99% and containing an amount of 6-{[6-(nitrooxy)hexanoyl]oxy}hexanoic acid (compound (IXa) equal to or lower than 0.2%.

The invention relates to clinical chemistry, in particular, to new biologically active compoundsamide derivatives of prostaglandin F2?. These compounds have low cytotoxicity and are capable of stimulating formation of endogenous nitrogen oxide in mammal cells. Synthesis of such compounds promotes expansion of nomenclature of biologically active derivatives of prostaglandin F2? capable of reducing intraocular pressure.

The present invention relates to a novel prostaglandin derivative having an alkynyl group on -chain, particularly, a novel prostaglandin derivative having a double bond at the 2-position and an alkynyl group on the -chain and a medicament containing the compound as an active ingredient.

According to the present invention, a compound represented by the formula (1) or a pharmaceutically acceptable salt thereof;

##STR00001## wherein each symbol is as defined in the present specification, or a cyclodextrin clathrate compound thereof, and a medicament containing the compound as an active ingredient, particularly, a medicament for the prophylaxis or treatment of a blood flow disorder associated with spinal canal stenosis or chronic arterial occlusion, can be provided.

Co-crystals comprising the Nuclear receptor related 1 protein-ligand binding domain (Nurr1-LBD) and a cyclopentenone prostaglandin are provided. Also provided are methods of identifying or designing Nurr1-modulating ligands and compounds based on the crystal structures described herein as well as the applications of said ligands and compounds as Nurr1 modulators or medicaments.

The subject of the invention is a process for the preparation of Latanoprostene bunod of formula (I) with a purity higher than 95% where chromatography is used applying normal phase gravity silica gel column chromatography where the used silica gel is irregular silica gel or spherical silica gel an as eluent and eluent mixture consisting of an apolar and a polar solvent is used and if desired, contamination of the purified compound of formula I arising from the solvents are removed by silica gel filtration chromatography.

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.