Chirality - A New Era of Therapeutics

Agrawal, Y. K.; Bhatt, Hardik; Raval, Hitesh G.; Oza, Pratik M.; Gogoi, Paramartha

doi:10.2174/138955707780619617

Cited by 42 publications

(29 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…4--c. Chiral Hetero--and Carbocycles Just as cyclic sulfones can be hydrogenated asymmetrically, so can a variety of hetero--and carbocycles, which find many uses including those in medical applications. 46 Generally, the enantioselective synthesis of chiral heterocycles with a stereocenter two or even three atoms away from the heteroatom is very difficult by other methods. Verendel et al 47 synthesized and asymmetrically hydrogenated a range of cyclic substrates (Scheme 11).…”

Section: Onementioning

confidence: 99%

Development of iridium-catalyzed asymmetric hydrogenation: New catalysts, new substrate scope

Cadu

Andersson

2012

Journal of Organometallic Chemistry

View full text Add to dashboard Cite

Development of iridium-catalyzed asymmetric hydrogenation: New catalysts, new substrate scope.. The asymmetric hydrogenation of olefins is a tremendously powerful tool used to synthesize chiral molecules. The field was pioneered using rhodium--and ruthenium--based catalysts; however, catalysts based on both of these metals suffer from limitations, such as the need for directing substituents near or even adjacent to the olefin. Iridium--based catalysts do not suffer from this flaw and can thus hydrogenate a wide variety of olefins, including some tetra substituted ones. It is also possible for iridium--based catalysts to hydrogenate hetero--π bonds such as those found in hetero--aromatic rings. This review summarizes the contributions made to this field by our research group over the past few years. Keywords: Asymmetric catalysis, Iridium, Hydrogenation, Alkenes Graphical Abstract: Journal of Organometallic Chemistry

show abstract

Section: Onementioning

confidence: 99%

Development of iridium-catalyzed asymmetric hydrogenation: New catalysts, new substrate scope

Cadu

Andersson

2012

Journal of Organometallic Chemistry

View full text Add to dashboard Cite

show abstract

“…Enantioselective pharmacokinetics often leads to enantioselective pharmacodynamics in terms of efficacy, toxicity, and clinical outcome. [3][4][5][6] Nateglinide, (2)-N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine, is a nonsulfonylurea oral insulinotropic agent (see Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of nateglinide enantiomers and their metabolites in Goto‐Kakizaki rats, a model for type 2 diabetes mellitus

et al. 2009

View full text Add to dashboard Cite

The pharmacokinetics of (-)-N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine (nateglinide) and its enantiomer (L-enantiomer) was studied in Goto-Kakizaki (GK) rats after intravenous administration of nateglinide or L-enantiomer at a dose of 40 micromol/kg body weight. Nateglinide, its L-enantiomer and their metabolites in serum, bile and urine were determined. The total clearance (CL(tot)) and the volume of distribution (Vd) was slightly higher for nateglinide than those for L-enantiomer in control rats, although the differences were not statistically significant. The cumulative excretions of L-M1 (major metabolite of L-enantiomer) and L-M2 (major metabolite of L-enantiomer) into bile were almost the same as that of M1 (major metabolite of nateglinide)and M2 (major metabolite of nateglinide). In GK rats, CL(tot) and Vd were higher for nateglinide than those for L-enantiomer. The cumulative excretion of L-M1 and L-M2 were not different from those of M1 and M2, respectively, into bile or urine. CL(tot) and Vd for nateglinide or L-enantiomer in GK rats were not different from those in control rats. The total excretion of M1, M2, L-M1, and L-M2 into bile or urine in GK rats was not substantially different from that of control rats. These results suggest that the L-enantiomer of nateglinide shows higher CL(tot) and Vd compared with nateglinide, especially in the diabetic state.

show abstract

“…Nowadays, a tendency to develop and test new drugs in the form of pure isomers is obvious (e.g. Agrawal et al 2007). In the case of 44Bu, the S-isomer has been recently observed to suppress the aconitine-induced arrhythmias more efficiently compared to the R-isomer whereas the racemate exerted the best effect in suppressing ventricular fibrillation (Bartosova et al 2008).…”

mentioning

confidence: 99%

Effect of Newly Synthesized Compounds 44Bu and 444 on QRS-Complex Width and Fast Sodium Current: Differences between Isomers

Kilianová

Bébarová

Beránková³

et al. 2010

Acta Vet. Brno

View full text Add to dashboard Cite

Two newly synthesized short-acting agents 44Bu and 444 were observed to suppress the aconitine-induced arrhythmias and block the fast sodium current I Na in the rat heart. No data about their effect on the electrocardiographic parameters are available. In this study, we explored the effect of both racemates and particular isomers of 44Bu and 444 on the QRS-complex width in vivo in rats and on I Na in isolated rat ventricular myocytes. All variants of 44Bu and 444 (1.5 mg/kg) caused a significant QRS-widening reaching the peak effect at the 1 st or 2 nd min after their intravenous administration. 44Bu racemate widened the QRS-complex from 16.8 ± 0.4 to 26.3 ± 0.5 ms (by 57%), significantly more than R-(33%-widening) and S-isomer (36%-widening). 444 racemate widened the QRS-complex from 20.8 ± 1.0 to 34.1 ± 0.9 ms (by 64%), which was comparable to S-isomer (63%-widening), however, substantially more than R-isomer (40%-widening). Regarding the effect on I Na , 44Bu caused a significantly deeper I Nablock compared to 444 when applied at the same concentration of 3 µmol/l (0.1 mg/kg). 44Bu racemate and R-isomer blocked I Na similarly (91.7 ± 0.8 and 91.8 ± 1.6%-block, respectively) and significantly more than S-isomer (82.4 ± 2.3%-block). 444 R-isomer blocked I Na less than racemate and S-isomer (by 31.7 ± 3.9% vs. 48.3 ± 4.7 and 50.2 ± 4.1%, respectively). We conclude that both racemates and particular isomers of 44Bu and 444 induce a QRS-widening and block I Na in the rat heart, however, their effects notably differed. The relative widening of the QRS-complex after application of 44Bu did not conform to the level of I Na -block observed in isolated cardiomyocytes which stresses the importance of in vivo experiments in the pre-clinical testing of new drugs.

show abstract

Chirality - A New Era of Therapeutics

Cited by 42 publications

References 0 publications

Development of iridium-catalyzed asymmetric hydrogenation: New catalysts, new substrate scope

Development of iridium-catalyzed asymmetric hydrogenation: New catalysts, new substrate scope

Pharmacokinetics of nateglinide enantiomers and their metabolites in Goto‐Kakizaki rats, a model for type 2 diabetes mellitus

Effect of Newly Synthesized Compounds 44Bu and 444 on QRS-Complex Width and Fast Sodium Current: Differences between Isomers

Contact Info

Product

Resources

About