15760-35-7Relevant academic research and scientific papers
Process for preparing 3 - methylene cyclobutyl derivative
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Paragraph 0016-0018; 0028-0032, (2021/10/13)
The invention provides a preparation method of 3 - methylene cyclobutyl derivatives, and uses propylene derivatives. Through screening of technological conditions such as polymerization inhibitor, reaction solvent and the like, the problem that propylene derivative polymerization blocks the reaction channel is solved while the product conversion rate is ensured.
Discovery of 4-[3-(trans-3-Dimethylaminocyclobutyl)-1H-indol-5-ylmethyl](4S)-oxazolidin- 2-one (4991W93), a 5HT1b/1d receptor partial agonist and a potent inhibitor of electrically induced plasma extravasation
Jandu,Barrett,Brockwell,Cambridge,Farrant,Foster,Giles,Glen,Hill,Hobbs,Honey,Martin,Salmon,Smith,Woollard,Selwood
, p. 681 - 693 (2007/10/03)
Utilizing a pharmacophoric model of binding of 3-(2-aminoethyl)indoles to 5HT1B/1D receptors, we identified the 3-aminocyclobutyl group as a potential ethylamine isostere. A novel multidimensional chemometric approach was used to predict the intrinsic activity (degree of agonism) at the receptor. A qualitative model for pharmacokinetic properties was then used to guide the synthesis toward molecules likely to have oral bioavailability in humans. A novel synthetic route to 3-(3-dimethylaminocyclobutyl)indoles was developed. Analogues showed generally lower intrinsic activity at 5HT1B/1D receptors than their ethylamine counterparts. 4-[3-(trans-3-Dimethylaminocyclobutyl)-1H-indol-5-ylmethyl]-(4S)-oxazolidin- 2-one (4991W93, 1) was identified as a partial agonist against 5HT1B/1D receptors, with low intrinsic activity. This molecule also has significant activity against 5HT1F receptors but is selective over other 5HT receptors. In addition this compound was found to be an exceptionally potent inhibitor of electrically induced plasma extravasation. Compound 1 may have utility in the treatment and prophylaxis of migraine.
Mechanism and Stereochemistry of General Acid Catalyzed Additions to Bicyclobutane
Hoz, Shmaryahu,Livneh, Mordechai,Cohen, Drora
, p. 4537 - 4544 (2007/10/02)
The electrophilic addition of MeOH across the central bond of 3-X-bicyclobutanecarbonitriles (X = H, Me, Cl) was found to be a general acid catalyzed reaction with Broensted α = 0.96.The ρ+ value of these reactions is -7.1 +/- 1.3.These two coefficients are interpreted as an indication of an unbalanced transition state.In the case of X = H and Me, the addition reaction is of syn stereochemistry.This is probably also the stereochemistry in the case X = Cl.However, the initialy formed adduct in this case reacts further to give ketal 3a.In the presence of NaClO4, anti addition products are also observed and reaction rates increase linearly with the concentration of the salt.Ab initio calculations (3-21G) show that protonated bicyclobutane has two stable geometries (Cs symmetry), one highly puckered and the other nearly planar.The first structure is more stable by 9.5 kcal/mol (6-31G*/3-21G).It is concluded that with strong nucleophiles, the syn stereochemistry results from a concerted attack by proton and the nucleophile from the equatorial directions.With weaker nucleophiles, the first step is protonation of the substrate which is followed by nucleophilic attack on the puckered cation.Both attacks take place from an equatorial direction leading therefore ultimately to the observed stereospecificity.
