The present disclosure relates to novel compounds, to said compounds for use as a medicine, more in particular for the prevention or treatment of diseases mediated by activity of YAP/TAZ-TEAD transcription, yet more in particular for the prevention or treatment of cancer or fibrosis. The present disclosure also relates to a method for the prevention or treatment of said diseases comprising the use of the novel compounds.

The present disclosure relates to novel compounds, to said compounds for use as a medicine, more in particular for the prevention or treatment of diseases mediated by activity of YAP/TAZ-TEAD transcription, yet more in particular for the prevention or treatment of cancer or fibrosis. The present disclosure also relates to a method for the prevention or treatment of said diseases comprising the use of the novel compounds.

The problem to be solved by the present invention is to provide a compound suitable for a pharmaceutical composition, specifically an agent for treating nocturia.

The inventors have assumed that inhibition of nocturnal activity of placental leucine aminopeptidase (P-LAP), i.e. aminopeptidase that cleaves AVP, would maintain and/or increase an endogenous AVP level to enhance the antidiuretic effect, which would contribute to a decreased number of nocturnal voids, and have extensively studied compounds which inhibit P-LAP. As a result, the inventors have found that (2R)-3-amino-2-(pyridylmethyl)-2-hydroxy-propanoic acid derivatives have excellent P-LAP inhibitory activity. The inventors have evaluated antidiuretic effects in water-loaded rats and have found that the compounds increase endogenous AVP levels by inhibiting P-LAP and consequently reduce urine production. The present invention therefore provides compounds expected to be used as an agent for treating nocturia based on P-LAP inhibition.

Therapeutic combinations of hepatitis B virus (HBV) vaccines and a capsid assembly modulator are described. Methods of inducing an immune response against HBV or treating an HBV-induced disease, particularly in individuals having chronic HBV infection, using the disclosed therapeutic combinations are also described.

Therapeutic combinations of hepatitis B virus (HBV) vaccines and a capsid assembly modulator are described. Methods of inducing an immune response against HBV or treating an HBV-induced disease, particularly in individuals having chronic HBV infection, using the disclosed therapeutic combinations are also described.

Benzimidazoles of formula (I): wherein: A is 5- to 12-membered aryl or 5- to 12-membered heteroaryl, each of which is unsubstituted or substituted; Y is a single bond, —(CH.sub.2).sub.p—, —X—, —CH.sub.2—X—, or —X—CH.sub.2—; X is —O—, —S—, —N(R.sup.2)—, >C═O, >S(═O), >S(═O).sub.2, —O—C(═O)—, —C(═O)—O—, N(R.sup.2)—C(═O)—, or —C(═O)—N(R.sup.2)—; each L is independently a single bond, C.sub.1-3alkylene, C.sub.2-3alkenylene or C.sub.2-3alkynylene; R.sup.1 is C.sub.1-6alkyl, C.sub.2-6alkenyl or C.sub.2-6alkynyl, each of which is unsubstituted or substituted; each Z is independently —N(R.sup.2).sub.2, —OR.sup.2, —SR.sup.2, —S(═O)R.sup.2, —S(═O).sub.2R.sup.2; each R.sup.2 is independently hydrogen, C.sub.1-6alkyl, C.sub.2-6alkenyl or C.sub.2-6 alkynyl, wherein said alkyl, alkenyl and alkynyl groups are unsubstituted or substituted; m is 0, 1, 2, or 3; n is 1, 2, or 3; and p is 1, 2, or 3; and the pharmaceutically acceptable salt thereof are inhibitors of RSV and can therefore be used to treat or prevent an RSV infection. ##STR00001##

Benzimidazoles of formula (I): wherein: A is 5- to 12-membered aryl or 5- to 12-membered heteroaryl, each of which is unsubstituted or substituted; Y is a single bond, —(CH.sub.2).sub.p—, —X—, —CH.sub.2—X—, or —X—CH.sub.2—; X is —O—, —S—, —N(R.sup.2)—, >C═O, >S(═O), >S(═O).sub.2, —O—C(═O)—, —C(═O)—O—, N(R.sup.2)—C(═O)—, or —C(═O)—N(R.sup.2)—; each L is independently a single bond, C.sub.1-3alkylene, C.sub.2-3alkenylene or C.sub.2-3alkynylene; R.sup.1 is C.sub.1-6alkyl, C.sub.2-6alkenyl or C.sub.2-6alkynyl, each of which is unsubstituted or substituted; each Z is independently —N(R.sup.2).sub.2, —OR.sup.2, —SR.sup.2, —S(═O)R.sup.2, —S(═O).sub.2R.sup.2; each R.sup.2 is independently hydrogen, C.sub.1-6alkyl, C.sub.2-6alkenyl or C.sub.2-6 alkynyl, wherein said alkyl, alkenyl and alkynyl groups are unsubstituted or substituted; m is 0, 1, 2, or 3; n is 1, 2, or 3; and p is 1, 2, or 3; and the pharmaceutically acceptable salt thereof are inhibitors of RSV and can therefore be used to treat or prevent an RSV infection. ##STR00001##

Provided herein are osmotic dosage forms containing deutetrabenazine for use in the treatment of, e.g., hyperkinetic movement disorders. When orally administered to a subject on a once-daily basis, the dosage forms provide a favorable pharmacokinetic profile for the active agent indicating treatment efficacy over an extended period of time.

The present invention provides compounds of formula I, pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting kinase (e.g., GSK3 (e.g., GSK3α or GSK3β) or CK1) activity. The present invention further provides methods of using the compounds described herein for treating kinase-mediated disorders, such as neurological diseases, psychiatric disorders, metabolic disorders, and cancer.

##STR00001##

The present invention provides compounds of formula I, pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting kinase (e.g., GSK3 (e.g., GSK3α or GSK3β) or CK1) activity. The present invention further provides methods of using the compounds described herein for treating kinase-mediated disorders, such as neurological diseases, psychiatric disorders, metabolic disorders, and cancer.

##STR00001##