1065609-70-2Relevant articles and documents
3-(1-OXO-5-(PIPERIDIN-4-YL)ISOINDOLIN-2-YL)PIPERIDINE-2,6-DIONE DERIVATIVES AND USES THEREOF
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Page/Page column 301, (2020/08/28)
The present disclosure provides a compound of Formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein R1, R2, R3, Rx, and n are as defined herein, and methods of making and using same.
INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL
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Paragraph 0215, (2016/10/06)
The present invention provides compounds of Formula Ia 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 conditions associated with excessive salt and water retention.
Development of orally active oxytocin antagonists: Studies on 1-(1-{4- [1-(2-methyl-1-oxidopyridin-3-ylmethyl)piperidin-4-yloxy].2methoxybenzoyl}- 4-yl)-1,4-dihydrobenz[d][1,3]oxazin-2-one (L-372,662) and related pyridines
Bell, Ian M.,Erb, Jill M.,Freidinger, Roger M.,Gallicchio, Steven N.,Guare, James P.,Guidotti, Maribeth T.,Halpin, Rita A.,Hobbs, Doug W.,Homnick, Carl F.,Kuo, Michelle S.,Lis, Edward V.,Mathre, David J.,Michelson, Stuart R.,Pawluczy, Joseph M.,Pettibone, Douglas J.,Reiss, Duane R.,Vickers, Stanley,Williams, Peter D.,Woyden, Carla J.
, p. 2146 - 2163 (2007/10/03)
The previously reported oxytocin antagonist L-371,257 (2) has been modified at its acetylpiperidine terminus to incorporate various pyridine N- oxide groups. This modification has led to the identification of compounds with improved pharmacokinetics and excellent oral bioavailability. The pyridine N-oxide series is exemplified by L-372,662 (30), which possessed good potency in vitro (Ki = 4.1 nM, cloned human oxytocin receptor) and in vivo (intravenous AD50 = 0.71 mg/kg in the rat), excellent oral bioavailability (90% in the rat, 96% in the dog), good aqueous solubility (>8.5 mg/mL at pH 5.2) which should facilitate formulation for iv administration, and excellent selectivity against the human arginine vasopressin receptors. Incorporation of a 5-fluoro substituent on the central benzoyl ring of this class of oxytocin antagonists enhanced in vitro and in vivo potency but was detrimental to the pharmacokinetic profiles of these compounds. Although lipophilic substitution around the pyridine ring of compound 30 gave higher affinity in vitro, such substituents were a metabolic liability and caused shortfalls in vivo. Two approaches to prevent this metabolism, addition of a cyclic constraint and incorporation of trifluoromethyl groups, were examined. The former approach was ineffective because of metabolic hydroxylation on the constrained ring system, whereas the latter showed improvement in plasma pharmacokinetics in some cases.
