Diphenyl ethers as androgen receptor antagonists for the topical suppression of sebum production

Endothelins (ETs) are potent vasoactive peptides critical in the human body's various physiological and pathological processes. One of the most promising therapeutic strategies for treating pulmonary arterial hypertension (PAH) involves counteracting the effects of these endothelins using a class of drugs known as endothelin receptor antagonists.
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme (ECE). Of...

Acne is a multifactorial skin condition primarily affecting adolescents and young adults, with a global prevalence estimated to exceed 75% in this demographic. The condition is characterized by the formation of comedones (blackheads and whiteheads), papules, pustules, nodules, and, in severe cases, cysts, particularly in areas rich in sebaceous glands such as the face, neck, chest, and back. The pathogenesis involves increased sebum production, follicular hyperkeratinization, colonization by...

A sebaceous gland is a type of oil gland found almost all over the skin ( except palms and soles) and helps lubricate and waterproof the skin and hair. Most sebaceous glands are associated with hair follicles. They generate and excrete sebum, a mixture of lipids, onto the skin surface, thereby naturally lubricating the dry and dead layer of keratinized cells of the stratum corneum, keeping it pliable.
These glands that produce the oils on the skin and hair are holocrine glands. The mature...

Adrenergic antagonists, or sympatholytics, inhibit adrenoceptor activation driven by catecholamines or agonists. Based on their adrenoceptor specificity, adrenergic blockers can be categorized into two primary groups: α-adrenergic blockers (α-blockers) and β-adrenergic blockers (β-blockers). α-blockers interact with α1 and α2 subtypes of α-adrenoceptors.
Nonselective α-blockers: Nonselective α-blockers contain haloalkylamine or imidazoline moieties. Phenoxybenzamine, with a haloalkylamine...

Adrenergic agonists' structure-activity relationship (SAR) determines their selectivity and efficacy. These agonists comprise a phenylethylamine moiety with an aromatic ring and an ethylamine side chain.
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of the aromatic...

Indirect-acting cholinergic agonists, or anticholinesterases, enhance the body's cholinergic activity by inhibiting acetylcholine's breakdown. They are categorized as reversible or irreversible agents based on their mechanism of action. They are further classified into short-acting, intermediate-acting, and long-acting agents based on their duration of action.
Reversible agents containing quaternary amines, such as neostigmine and edrophonium, are not easily absorbed orally because they are...