Abstract: The present invention relates to novel spirobicyclic analogues of Formula (I) wherein the variables have the meaning defined in the claims. The compounds according to the present invention are useful as PRMT5 inhibitors. The invention further relates to pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.

Abstract: The present disclosure provides methods for treating a human patient diagnosed with a cancer, comprising administering a therapeutically effective amount of a PR.MTS (protein arginine methyltransferase 5) inhibitor, certain methods comprising (i) administering to the patient initial doses of at least about 0.1 mg per day of the PRMT5 inhibitor that is (1S,2R,3 S,SR)-3-(2-(2-amino-3-bromoquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol or a pharmaceutically acceptable addition salt or solvate thereof for an initial dosing period of about 5 to about 20 days; and (ii) administering to the patient subsequent doses of at least about 0.1 mg per day of the PRMT5 inhibitor for one or more subsequent dosing periods of about 5 to about 20 days each. In these methods, a first subsequent dosing period is separated in time from the initial dosing period by at least about 5 days and the subsequent dosing periods are separated in time from each other by at least about 5 days.

Abstract: The present disclosure related to compounds that can be useful as inhibitors of PD-1, PD-L1 or the PD-1/PD-L1 interaction. Also disclosed herein are pharmaceutical compositions of that can include a compound of Formula (I), or a pharmaceutically acceptable salt thereof, and uses of or methods of using a compound of Formula (I), or a pharmaceutically acceptable salt thereof, for the treatment of PD-L1 related diseases including but not limited to liver diseases, cancer, hepatocellular carcinoma, viral diseases, or hepatitis B.

Abstract: The present invention relates novel 6-6 bicyclic aromatic ring substituted nucleoside analogues of Formula (I) wherein the variables have the meaning defined in the claims. The compounds according to the present invention are useful as PRMT5 inhibitors. The invention further relates to pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.

Abstract: The present disclosure related to compounds that can be useful as inhibitors of PD-1, PD-L1 or the PD-1/PD-L1 interaction. Also disclosed herein are pharmaceutical compositions of that can include a compound of Formula (I), or a pharmaceutically acceptable salt thereof, and uses of or methods of using a compound of Formula (I), or a pharmaceutically acceptable salt thereof, for the treatment of PD-L1 related diseases including but not limited to liver diseases, cancer, hepatocellular carcinoma, viral diseases, or hepatitis B.

Abstract: The present disclosure provides methods for treating a human patient diagnosed with a cancer, comprising administering a therapeutically effective amount of a PRMT5 (protein arginine methyltransferase 5) inhibitor, certain methods comprising (i) administering to the patient initial doses of at least about 0.1 mg per day of the PRMT5 inhibitor that is (1S,2R,3S,5R)-3-(2-(2-amino-3-bromoquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol or a pharmaceutically acceptable addition salt or solvate thereof for an initial dosing period of about 5 to about 21 days; and (ii) administering to the patient subsequent doses of at least about 0.1 mg per day of the PRMT5 inhibitor for one or more subsequent dosing periods of about 5 to about 21 days each. In these methods, a first subsequent dosing period is separated in time from the initial dosing period by at least about 5 days and the subsequent dosing periods are separated in time from each other by at least about 5 days.

Abstract: The present disclosure related to compounds that can be useful as inhibitors of PD-1, PD-L1 or the PD-1/PD-L1 interaction. Also disclosed herein are pharmaceutical compositions of that can include a compound of Formula (I), or a pharmaceutically acceptable salt thereof, and uses of or methods of using a compound of Formula (I), or a pharmaceutically acceptable salt thereof, for the treatment of PD-L1 related diseases including but not limited to liver diseases, cancer, hepatocellular carcinoma, viral diseases, or hepatitis B.

Abstract: The present disclosure related to compounds that can be useful as inhibitors of PD-1, PD-L1 or the PD-1/PD-L1 interaction. Also disclosed herein are pharmaceutical compositions of that can include a compound of Formula (I), or a pharmaceutically acceptable salt thereof, and uses of or methods of using a compound of Formula (I), or a pharmaceutically acceptable salt thereof, for the treatment of PD-L1 related diseases including but not limited to liver diseases, cancer, hepatocellular carcinoma, viral diseases, or hepatitis B.

Abstract: Disclosed are compounds, compositions and methods for treating of diseases, syndromes, conditions, and disorders that are affected by the modulation of MALT1. Such compounds are represented by Formula (I) as follows: wherein R1, R2, R3, R4, R5, R6, R5, G1, and G2 are defined herein.

Abstract: Disclosed are compounds, compositions and methods for treating of diseases, syndromes, conditions, and disorders that are affected by the modulation of MALT1. Such compounds are represented by Formula (I) as follows: wherein the variables are defined herein.

Abstract: Embodiments of the present invention relate to 6-6 bicyclic aromatic ring substituted nucleoside analogues, including, for example, the following compound: Embodiments of the present invention also relate to uses of the disclosed compounds for the inhibition of protein arginine methyltransferase 5 (PRMT5).

Abstract: The present invention relates to novel spirobicyclic analogues of Formula (I) wherein the variables have the meaning defined in the claims. The compounds according to the present invention are useful as PRMT5 inhibitors. The invention further relates to pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.

Abstract: The present invention relates to novel novel monocyclic and bicyclic ring system substituted carbanucleoside analogues of Formula (I), wherein the variables have the meaning defined in the claims. The compounds according to the present invention are useful as PRMT5 inhibitors. The invention further relates to pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.

Abstract: The present invention relates to novel novel monocyclic and bicyclic ring system substituted carbanucleoside analogues of Formula (I) wherein the variables have the meaning defined in the claims. The compounds according to the present invention are useful as PRMT5 inhibitors. The invention further relates to pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.

Abstract: The present invention relates to novel spirobicyclic analogues of Formula (I) wherein the variables have the meaning defined in the claims. The compounds according to the present invention are useful as PRMT5 inhibitors. The invention further relates to pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.

Abstract: Disclosed are compounds, compositions and methods for treating of diseases, syndromes, conditions, and disorders that are affected by the modulation of MALT1. Such compounds are represented by Formula (I) as follows: wherein R1, R2, R3, R4, R5, and G, are defined herein.

Abstract: Disclosed are compounds, compositions and methods for treating of diseases, syndromes, conditions, and disorders that are affected by the modulation of MALT1. Such compounds are represented by Formula (I) as follows: wherein R1, R2, R3, R4, R5, R6, R5, G1, and G2 are defined herein.

Abstract: The present invention relates novel substituted nucleoside analogues of Formula (I) wherein the variables have the meaning defined in the claims. The compounds according to the present invention are useful as PRMT5 inhibitors. The invention further relates to pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.

Abstract: Disclosed are compounds, compositions and methods for treating of diseases, syndromes, conditions, and disorders that are affected by the modulation of MALT1. Such compounds are represented by Formula (I) as follows: wherein R1, R2, R3, R4, R5, R6, R7, G1 and G2, are defined herein.

Abstract: The present disclosure provides methods for treating a human patient diagnosed with a cancer, comprising administering a therapeutically effective amount of a PRMT5 (protein arginine methyltransferase 5) inhibitor, certain methods comprising (i) administering to the patient initial doses of at least about 0.1 mg per day of the PRMT5 inhibitor that is (1S,2R,3S,5R)-3-(2-(2-amino-3-bromoquinolin-7-yl)ethyl)-5-(4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol or a pharmaceutically acceptable addition salt or solvate thereof for an initial dosing period of about 5 to about 21 days; and (ii) administering to the patient subsequent doses of at least about 0.1 mg per day of the PRMT5 inhibitor for one or more subsequent dosing periods of about 5 to about 21 days each. In these methods, a first subsequent dosing period is separated in time from the initial dosing period by at least about 5 days and the subsequent dosing periods are separated in time from each other by at least about 5 days.