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 RORγt inhibitor as well as a preparation method thereof and uses thereof, and a pharmaceutical composition including the compound, a method for preparing the pharmaceutical composition, and use of the compound or the pharmaceutical composition in the treatment or prevention of RORγt-mediated cancer, inflammation, or autoimmune diseases in mammals, especially humans.

A RORγt inhibitor as well as a preparation method thereof and uses thereof, and a pharmaceutical composition including the compound, a method for preparing the pharmaceutical composition, and use of the compound or the pharmaceutical composition in the treatment or prevention of RORγt-mediated cancer, inflammation, or autoimmune diseases in mammals, especially humans.

A preparation method of a high-optical-purity chiral oxo-aza-cycloalkane compound comprises the steps of: (R or S)N-substituent P-2-alkoxycarbonylalkyliminodiacetic acid diester as the raw material is cyclized in the presence of a solvent and a cyclization reagent (lewis acid-lewis base) to obtain high-optical-purity N-substituent P -2- (R or S)- substituent G oxo-aza-cycloalkane or the salt thereof through thermal decarboxylation or hydrolysis decarboxylation reaction; the specific type of cyclization reagent used in the present invention is conductive to the preparation of the high-optical-purity target product, easily recoverable, with reduced waste liquid discharge, green, and environment-friendly, which contributes to green industrial production.

A preparation method of a high-optical-purity chiral oxo-aza-cycloalkane compound comprises the steps of: (R or S)N-substituent P-2-alkoxycarbonylalkyliminodiacetic acid diester as the raw material is cyclized in the presence of a solvent and a cyclization reagent (lewis acid-lewis base) to obtain high-optical-purity N-substituent P -2- (R or S)- substituent G oxo-aza-cycloalkane or the salt thereof through thermal decarboxylation or hydrolysis decarboxylation reaction; the specific type of cyclization reagent used in the present invention is conductive to the preparation of the high-optical-purity target product, easily recoverable, with reduced waste liquid discharge, green, and environment-friendly, which contributes to green industrial production.

The present disclosure provides, inter alia, compounds with MASP-2 inhibitory activity, compositions of such compounds, and methods of making and using such compounds.

The present disclosure provides, inter alia, compounds with MASP-2 inhibitory activity, compositions of such compounds, and methods of making and using such compounds.

The present invention generally relates to new compounds for therapeutic uses. In particular, the disclosed series compounds with immunomodulatory activities are useful for treatment of dysfunctions of the immune system and various cancers. Pharmaceutical composition matters and methods for treating a patient with an immune disease and/or a cancer by administering therapeutically effective amounts of such compound alone or together with other therapeutics are within the scope of this disclosure.

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.

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