Synthesis and central nervous system depressant activity of some 5-(2-substituted alkyl)-2-oxazolidinones

Fielden, Marvel L.; Welstead, William J.; Dawson, Norman D.; Chen, Ying-Ho; Mays, Richard P.; DaVanzo, John P.; Lunsford, Carl D.

doi:10.1021/jm00268a012

Cited by 5 publications

(3 citation statements)

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“…Preparation of Chiral l-Methyl-3-pyrrolidinols. (S)-3-Hydroxy-l-methyl-2,5-pyrrolidinedione (4). To a stirred solution of 134 g (1 mol) of (S)-malic acid in 700 mL of toluene was added 97 mL of 40% aqueous CH3NH2.…”

Section: Methodsmentioning

confidence: 99%

“…The combined organic extracts were washed 2 X 100 mL with H20, dried (Na2S04), and concentrated. The residue crystallized from toluene-(t-Pr)20 to yield 4]oxazepin-ll-one (22). A solution of 50 g (0.43 mol) of 2-(hydroxymethyl)-l-methylpyrrolidine and 67.8 g (0.43 mol) of 2-chloronicotinic acid in 250 mL of dry DMF was added over a period of 45 min to a stirred suspension of 36.1 g (0.9 mol) of 60% NaH-mineral oil in 300 mL of dry DMF at 55 °C.…”

Section: Methodsmentioning

confidence: 99%

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Optical isomers of rocastine and close analogs: synthesis and H1 antihistaminic activity of its enantiomers and their structural relationship to the classical antihistamines

Sleevi

Cale²,

Gero³

et al. 1991

J. Med. Chem.

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The enantiomers of 2-[2-(dimethylamino)ethyl]-3,4-dihydro-4-methylpyrido[3,2-f]-1,4- oxazapine-5(2H)-thione (rocastine) and two of its more potent analogues were prepared with an enantiomeric purity of greater than 99.9%. The antihistaminic activity of these compounds was assessed by their ability to block histamine-induced lethality in guinea pigs and to inhibit [3H]mepyramine binding to guinea pig cortex. In this series, compounds having the R configuration at the 2-position are at least 300 times more potent than the S isomers. Conformational analysis and molecular modeling suggest that rocastine can adopt a conformation in which the pyridine ring, ether oxygen, and protonated amine functions are positioned similarly to the corresponding elements of the probable binding conformers of some of the more classical antihistamines. This conformation, boatlike in the oxazepine ring with the side chain quasi-equatorial and folded back toward the ring, is the likely binding conformer at the histamine H1 receptor, and the available structure-activity relationship data is consistent with this interpretation.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Optical isomers of rocastine and close analogs: synthesis and H1 antihistaminic activity of its enantiomers and their structural relationship to the classical antihistamines

Sleevi

Cale²,

Gero³

et al. 1991

J. Med. Chem.

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show abstract

“…C. Urethanes Heating 3-hydroxypyrrolidine (36) with diphenyl carbonate gave only linear polyurethane and no Nbridgehead bicyclic urethane. 25 Similarly, Schaefgen, Koontz, and Tietz37 obtained only linear polyurethane 39 and no bicyclic monomer from the chloroformate of 4-hydroxypiperidine (38). The diphenyl carbonate method also did not give bicyclic product.…”

Section: Ring-opening Polymerizationmentioning

confidence: 97%