The present invention relates to a medicament for treating or preventing a disease related to orexin receptor, especially orexin type 2 receptor, comprising a new compound having a urea structure or a pharmaceutically acceptable salt thereof as an active ingredient. In more detail, the present invention relates to a medicament for treating or preventing narcolepsy, idiopathic hypersomnia, hypersomnia, sleep apnea syndrome, etc.

The present invention provides a process for preparing (R)-6-(tert-butoxycarbonyl)-6-azaspiro[2.5]octane-5-carboxylic acid (SM1), said process comprising the step of: iv) converting a compound of formula (VII) into a compound of formula (VIII) using a Wittig reagent in a suitable solvent; v) reacting through the Makosza reaction the compound of Formula (VIII) using bromoform and a suitable base to obtain cyclopropane compound of Formula (IX); and vi) removing bromine atoms in the presence of a reducing agent and a base in an alcoholic solvent thus obtaining (SM1). The invention relates also to a process for the conversion of the compound (SM1) for preparing (R)-4-(1-(6-(4-(trifluoromethyl)benzyl)-6-azaspiro[2.5]octane-5-carboxamido)cyclopropyl) benzoic acid (IV) or a salt thereof. The salt is preferably the sodium salt, more preferably the polymorphic form A of sodium (R)-4-(1-(6-(4-(trifluoromethyl)benzyl)-6-azaspiro[2.5]octane-5-carboxamido)-cyclopropyl) benzoate characterized by a powder XRD spectrum with peaks at values of the angle 2θ+0.2° of 4.3, 5.0, 5.8, 6.4, 7.1, 8.3, 8.7, 12.8, 15.3, 15.9.

The present invention provides a process for preparing (R)-6-(tert-butoxycarbonyl)-6-azaspiro[2.5]octane-5-carboxylic acid (SM1), said process comprising the step of: iv) converting a compound of formula (VII) into a compound of formula (VIII) using a Wittig reagent in a suitable solvent; v) reacting through the Makosza reaction the compound of Formula (VIII) using bromoform and a suitable base to obtain cyclopropane compound of Formula (IX); and vi) removing bromine atoms in the presence of a reducing agent and a base in an alcoholic solvent thus obtaining (SM1). The invention relates also to a process for the conversion of the compound (SM1) for preparing (R)-4-(1-(6-(4-(trifluoromethyl)benzyl)-6-azaspiro[2.5]octane-5-carboxamido)cyclopropyl) benzoic acid (IV) or a salt thereof. The salt is preferably the sodium salt, more preferably the polymorphic form A of sodium (R)-4-(1-(6-(4-(trifluoromethyl)benzyl)-6-azaspiro[2.5]octane-5-carboxamido)-cyclopropyl) benzoate characterized by a powder XRD spectrum with peaks at values of the angle 2θ+0.2° of 4.3, 5.0, 5.8, 6.4, 7.1, 8.3, 8.7, 12.8, 15.3, 15.9.

The present invention provides a pharmaceutical combination comprising the EP4 antagonist of Formula (R)-4-(1-(6-(4-(trifluoromethyl)benzyl)-6-azaspiro[2.5]octane-5-carboxamido)cyclopropyl)-benzoic acid or a pharmaceutically acceptable salt thereof and at least one immune checkpoint inhibitor, preferably the sodium salt of (R)-4-(1-(6-(4-(trifluoromethyl)benzyl)-6-azaspiro[2.5]octane-5-carboxamido)cyclopropyl) benzoic acid. A polymorphic form A of sodium salt of (R)-4-(1-(6-(4-(trifluoromethyl) benzyl)-6-azaspiro[2.5]octane-5-carboxamido)cyclopropyl)benzoate characterized by a powder XRD spectrum with peaks at values of the angle 2θ ±0.2° of 4.3, 5.0, 5.8, 6.4, 7.1, 8.3, 8.7, 12.8, 15.3, 15.9 is also described. The combination and the polymorphic form A are described for use in the treatment of tumours.

The present invention provides a pharmaceutical combination comprising the EP4 antagonist of Formula (R)-4-(1-(6-(4-(trifluoromethyl)benzyl)-6-azaspiro[2.5]octane-5-carboxamido)cyclopropyl)-benzoic acid or a pharmaceutically acceptable salt thereof and at least one immune checkpoint inhibitor, preferably the sodium salt of (R)-4-(1-(6-(4-(trifluoromethyl)benzyl)-6-azaspiro[2.5]octane-5-carboxamido)cyclopropyl) benzoic acid. A polymorphic form A of sodium salt of (R)-4-(1-(6-(4-(trifluoromethyl) benzyl)-6-azaspiro[2.5]octane-5-carboxamido)cyclopropyl)benzoate characterized by a powder XRD spectrum with peaks at values of the angle 2θ ±0.2° of 4.3, 5.0, 5.8, 6.4, 7.1, 8.3, 8.7, 12.8, 15.3, 15.9 is also described. The combination and the polymorphic form A are described for use in the treatment of tumours.

A light-receiving device in which an increase in driving voltage is inhibited is provided. Any of the following light-receiving devices is provided: a light-receiving device that includes a light-receiving layer between a pair of electrodes and in which the light-receiving layer includes an active layer, a buffer layer, and an electron-transport layer, the buffer layer is between the active layer and the electron-transport layer and is in contact with the active layer, and the buffer layer includes an organic compound having an electron-withdrawing group; a light-receiving device that includes a light-receiving layer between a pair of electrodes and in which the light-receiving layer includes an active layer, a buffer layer, and an electron-transport layer, the buffer layer is between the active layer and the electron-transport layer and is in contact with the active layer, and the buffer layer includes a heteroaromatic compound having an electron-withdrawing group.

A light-receiving device in which an increase in driving voltage is inhibited is provided. Any of the following light-receiving devices is provided: a light-receiving device that includes a light-receiving layer between a pair of electrodes and in which the light-receiving layer includes an active layer, a buffer layer, and an electron-transport layer, the buffer layer is between the active layer and the electron-transport layer and is in contact with the active layer, and the buffer layer includes an organic compound having an electron-withdrawing group; a light-receiving device that includes a light-receiving layer between a pair of electrodes and in which the light-receiving layer includes an active layer, a buffer layer, and an electron-transport layer, the buffer layer is between the active layer and the electron-transport layer and is in contact with the active layer, and the buffer layer includes a heteroaromatic compound having an electron-withdrawing group.

The present invention provides compounds of Formula (I) which can be used as CCR8 inhibitors, which can be used as treatment or prevention of cancer using CCR8 inhibitors targeted tumor specific T regulatory cells.

##STR00001##

In its many embodiments, the present invention provides certain substituted aryl and heteroaryl ether compounds of the Formula (I): and pharmaceutically acceptable salts thereof, wherein X, R.sup.1, R.sup.2, R.sup.3, L, R.sup.4, L.sub.1, Q, and R.sup.5 are as defined herein. The novel compounds of the invention, and pharmaceutically acceptable compositions comprising a compound thereof, are useful as Liver X-β receptor (LXRβ) agonists, and may be useful for treating or preventing pathologies related thereto. Such pathologies include, but are not limited to, inflammatory diseases and diseases characterized by defects in cholesterol and lipid metabolism, such as Alzheimer's disease. ##STR00001##

In its many embodiments, the present invention provides certain substituted aryl and heteroaryl ether compounds of the Formula (I): and pharmaceutically acceptable salts thereof, wherein X, R.sup.1, R.sup.2, R.sup.3, L, R.sup.4, L.sub.1, Q, and R.sup.5 are as defined herein. The novel compounds of the invention, and pharmaceutically acceptable compositions comprising a compound thereof, are useful as Liver X-β receptor (LXRβ) agonists, and may be useful for treating or preventing pathologies related thereto. Such pathologies include, but are not limited to, inflammatory diseases and diseases characterized by defects in cholesterol and lipid metabolism, such as Alzheimer's disease. ##STR00001##