392331-66-7Relevant articles and documents
SSTR5 ANTAGONISTS
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, (2021/06/11)
This disclosure is directed, at least in part, to SSTR5 antagonists useful for the treatment of conditions or disorders involving the gut-brain axis. In some embodiments, the SSTR5 antagonists are gut-restricted compounds. In some embodiments, the condition or disorder is a metabolic disorder, such as diabetes, obesity, nonalcoholic steatohepatitis (NASH), or a nutritional disorder such as short bowel syndrome.
4-Aryl-1-oxa-4,9-diazaspiro[5.5]undecane Derivatives as Dual μ-Opioid Receptor Agonists and σ1 Receptor Antagonists for the Treatment of Pain
García, Mónica,Virgili, Marina,Alonso, Mònica,Alegret, Carles,Fernández, Bego?a,Port, Adriana,Pascual, Rosalía,Monroy, Xavier,Vidal-Torres, Alba,Serafini, María-Teresa,Vela, José Miguel,Almansa, Carmen
, p. 2434 - 2454 (2019/12/25)
The synthesis and pharmacological activity of a new series of 1-oxa-4,9-diazaspiro[5.5]undecane derivatives as potent dual ligands for the sigma-1 receptor (σ1R) and the μ-opioid receptor (MOR) are reported. The different positions of the central scaffold, designed using a merging strategy of both target pharmacophores, were explored using a versatile synthetic approach. Phenethyl derivatives in position 9, substituted pyridyl moieties in position 4 and small alkyl groups in position 2 provided the best profiles. One of the best compounds, 15au, showed a balanced dual profile (i.e., MOR agonism and sigma antagonism) and a potent analgesic activity, comparable to the MOR agonist oxycodone in the paw pressure test in mice. Contrary to oxycodone, as expected from the addition of σ1R antagonism, 15au showed local, peripheral activity in this test, which was reversed by the σ1R agonist PRE-084. At equianalgesic doses, 15au showed less constipation than oxycodone, providing evidence that dual MOR agonism and σ1R antagonism may be a useful strategy for obtaining potent and safer analgesics.
INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL
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, (2016/05/19)
The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.
