The present invention provides a compound having a cholinergic muscarinic M1 receptor positive allosteric modulator activity and useful as an agent for the prophylaxis or treatment of Alzheimer's disease, schizophrenia, pain, sleep disorder, Parkinson's disease dementia, dementia with Lewy bodies, and the like.

The present invention relates to a compound represented by the formula (I) or a salt thereof.

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wherein each symbol is as described in the specification, or a salt thereof.

The present invention provides a compound having a cholinergic muscarinic M1 receptor positive allosteric modulator activity and useful as an agent for the prophylaxis or treatment of Alzheimer's disease, schizophrenia, pain, sleep disorder, Parkinson's disease dementia, dementia with Lewy bodies, and the like.

The present invention relates to a compound represented by the formula (I) or a salt thereof.

##STR00001##

wherein each symbol is as described in the specification, or a salt thereof.

The present disclosure relates to bifunctional compounds, which find utility as modulators of α-synuclein (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon. Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

The present disclosure relates to bifunctional compounds, which find utility as modulators of α-synuclein (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon. Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

A method of producing induced exosomes, the method comprising: contacting an isolated population of stem cells with an amount of a prostaglandin E receptor 4 (EP4) antagonist effective for inducing release of exosomes, whereby induced exosomes are released from the stem cells, and isolating the induced exosomes.

A method of producing induced exosomes, the method comprising: contacting an isolated population of stem cells with an amount of a prostaglandin E receptor 4 (EP4) antagonist effective for inducing release of exosomes, whereby induced exosomes are released from the stem cells, and isolating the induced exosomes.

The present invention relates to a pharmaceutical combination comprising (i) firibastat, (ii) a diuretic and (iii) a blocker of the systemic renin-angiotensin system selected from the group consisting of angiotensin I converting enzyme inhibitors (ACEIs) and angiotensin II receptor type 1 (AT1R) antagonists. Said composition is particularly useful for the treatment of hypertension and related diseases and conditions.

The present invention relates to a pharmaceutical combination comprising (i) firibastat, (ii) a diuretic and (iii) a blocker of the systemic renin-angiotensin system selected from the group consisting of angiotensin I converting enzyme inhibitors (ACEIs) and angiotensin II receptor type 1 (AT1R) antagonists. Said composition is particularly useful for the treatment of hypertension and related diseases and conditions.

Provided herein is a topical combination composition comprising tapinarof, a PDE4 inhibitor and optionally at least one additional active agent selected from a retinoid, benzoyl peroxide (BPO), a Janus kinase inhibitor (JAK inhibitor), a corticosteroid of potency class 1-4, an acaricide and combinations thereof. The active agents in the composition of this invention are in encapsulated or non-encapsulated form, according to need. The above compositions are useful for the treatment, prevention or alleviation of a skin disorder selected from psoriasis, dermatitis, acne, rosacea, ichthyosis, scaling skin, imbalance of skin barrier and tinea and exhibit synergistic and/or additive effects allowing to reduce the active agents amounts in the combination compositions.

Provided herein is a topical combination composition comprising tapinarof, a PDE4 inhibitor and optionally at least one additional active agent selected from a retinoid, benzoyl peroxide (BPO), a Janus kinase inhibitor (JAK inhibitor), a corticosteroid of potency class 1-4, an acaricide and combinations thereof. The active agents in the composition of this invention are in encapsulated or non-encapsulated form, according to need. The above compositions are useful for the treatment, prevention or alleviation of a skin disorder selected from psoriasis, dermatitis, acne, rosacea, ichthyosis, scaling skin, imbalance of skin barrier and tinea and exhibit synergistic and/or additive effects allowing to reduce the active agents amounts in the combination compositions.