Dual neurokinin NK1/NK2 antagonists: N-[(R,R)-(E)-1-arylmethyl-3-(2-oxo-azepan-3-yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamides and 3-[N′-3,5-bis(trifluoromethyl)benzoyl-N-arylmethyl-N′-methylhydrazino]-N-[(R)-2-oxo-azepan-3-yl]propionamides

Dual tachykinin NK1/NK2antagonist DNK333 inhibits neurokinin A‐induced bronchoconstriction in asthma patients

“…DNK333 is a dual NK 1 /NK 2 tachykinin receptor antagonist. In ligand binding studies DNK333 binds to cloned human tachykinin NK 1 and NK 2 receptors with similar affinity (inhibitory concentration at 50% values 4.8 and 5.5 nM) [19]. At the start of our study the specificity of DNK333 for tachykinin receptors had been studied in vivo in animals and in vitro on human colonic mucosa cells.…”

“…In addition, DNK333 inhibited bronchoconstriction induced by tachykinin NK 1 -and NK 2 -receptor agonists in guinea pigs and squirrel monkeys [19][20][21]. The present investigation utilised a randomised, double-blind, placebo-controlled, two-treatment crossover design to examine the effects of DNK333 on neurokinin A-induced bronchoconstriction in patients with asthma.…”

Pharmacological Potential of Benzamide Analogues and their Uses in Medicinal Chemistry

“…Some of the compounds were found to be more potent than nibentan and possessed a longer duration of action. The antifibrillatory activity of (±)-N-[5-(diethylamino)-1-(4-methoxyphenyl) pentyl]-4-nitrobenzamide hydrochloride was comparable to that of nibentan but exceeded the potency of D-satalol and sematilide [34,35].…”

Randomised clinical trial: the clinical effects of a novel neurokinin receptor antagonist, DNK333, in women with diarrhoea-predominant irritable bowel syndrome

“…DNK333, a novel drug that antagonises the NK 1 , NK 2 and NK 3 receptors, appears to be a candidate agent for use in IBS‐D 26, 27 . In preclinical studies, DNK333 has demonstrated the ability to normalise exaggerated motor and secretory function in the GI tract and to relieve abdominal pain/discomfort, without mediating changes in normal gut function (Data on file, Novartis).…”