A method of synthesizing a heteropolycycle, the method involving: reacting a bisepoxide with a first heteroatom nucleophile, to obtain a mixture comprising a diol compound; and further processing, to obtain the heteropolycycle with at least two heteroatoms within its polycyclic backbone, wherein each nitrogen within the polycyclic backbone of the heteropolycycle is introduced into the polycyclic backbone via an amine nucleophile.

The invention relates to a CDK4/6 kinase inhibitor, or a pharmaceutically acceptable salt, ester, or solvate thereof, or their isomers; a pharmaceutical formulation, pharmaceutical composition and kit comprising said CDK4/6 kinase inhibitor, or a pharmaceutically acceptable salt, ester, or solvate thereof, or their isomers, and use of said CDK4/6 kinase inhibitor, or a pharmaceutically acceptable salt, ester, or solvate thereof, or their isomers. For example, the compounds of the invention are useful for reducing or inhibiting the activity of CDK4/6 kinase in a cell, and/or treating and/or preventing a cancer-related disease mediated by CDK4/6 kinase.

The invention relates to a CDK4/6 kinase inhibitor, or a pharmaceutically acceptable salt, ester, or solvate thereof, or their isomers; a pharmaceutical formulation, pharmaceutical composition and kit comprising said CDK4/6 kinase inhibitor, or a pharmaceutically acceptable salt, ester, or solvate thereof, or their isomers, and use of said CDK4/6 kinase inhibitor, or a pharmaceutically acceptable salt, ester, or solvate thereof, or their isomers. For example, the compounds of the invention are useful for reducing or inhibiting the activity of CDK4/6 kinase in a cell, and/or treating and/or preventing a cancer-related disease mediated by CDK4/6 kinase.

The invention relates to a CDK4/6 kinase inhibitor, or a pharmaceutically acceptable salt, ester, or solvate thereof, or their isomers; a pharmaceutical formulation, pharmaceutical composition and kit comprising said CDK4/6 kinase inhibitor, or a pharmaceutically acceptable salt, ester, or solvate thereof, or their isomers, and use of said CDK4/6 kinase inhibitor, or a pharmaceutically acceptable salt, ester, or solvate thereof, or their isomers. For example, the compounds of the invention are useful for reducing or inhibiting the activity of CDK4/6 kinase in a cell, and/or treating and/or preventing a cancer-related disease mediated by CDK4/6 kinase.

Described are pharmacological compositions comprising a gum resin; a pharmacologically active agent and a topically acceptable volatile solvent for the gum resin and active agent. Also described are methods for the transdermal or transmucosal delivery of a pharmacologically active agent using such compositions.

Described are pharmacological compositions comprising a gum resin; a pharmacologically active agent and a topically acceptable volatile solvent for the gum resin and active agent. Also described are methods for the transdermal or transmucosal delivery of a pharmacologically active agent using such compositions.

According to the invention there is provided a compound of formula A1 which may be useful in the treatment of a condition or disorder ameliorated by the inhibition of the A.sub.1-A.sub.21, or, particularly, the A.sub.2, receptor wherein the compound of formula A1 has the structure, wherein, A represents Cy.sup.1 or Het.sup.A; Cy.sup.1 represents a 5- to 14-membered aromatic, fully saturated or partially unsaturated carbocylic ring system comprising one, two or three rings, which Cy.sup.1 group is optionally substituted by one or more R.sup.4a substituents; Het.sup.A represents a 5- to 14-membered heterocyclic group that may be aromatic, fully saturated or partially unsaturated, and which contains one or more heteroatoms selected from O, S and N, which heterocyclic group may comprise one, two or three rings and which HetA group is optionally substituted by one or more R4b substituents; B represents a Cy.sup.2 or Het.sup.B; Cy.sup.2 represents a 3- to 10-membered aromatic, fully saturated or partially unsaturated carbocyclic ring system comprising one or two rings, which Cy.sup.2 group is optionally substituted by one or more R.sup.4c substituents; Het.sup.B represents a 3- to 10-membered heterocyclic group that may be aromatic, fully saturated or partially unsaturated, and which contains one or more heteroatoms selected from O, S and N, which heterocyclic group may comprise one or two rings and which Het.sup.B group is optionally substituted by one or more R.sup.4d substituents.

##STR00001##

The present invention relates generally to compositions and methods for treating cancer and neoplastic disease. Provided herein are substituted heterocyclic derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of lysine specific demethylase-1. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, lung cancer and/or melanoma and the like.

The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.

##STR00001##

The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.

##STR00001##