The enantiomers of the teratogenic thalidomide analogue EM 12

Schmahl, Hans-Josef; Heger, Wolfgang; Nau, Heinz

doi:10.1016/0378-4274(89)90155-0

Cited by 31 publications

(8 citation statements)

References 9 publications

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“…If hydrolysis of the phthalimide moiety leads to inactivation of thalidomide, then 5c is also expected to be more active than 1 . Several studies have suggested that thalidomide is a prodrug and hepatic hydroxylation is essential for activities such as teratogenicity or inhibition of angiogenesis. , In order to investigate the likelihood that metabolic hydroxylation is required for antitumor activity, derivatives of 5c ( 5a , b ) that underwent aromatic hydroxylation on the benzene ring of the phthalimidino group were prepared and assessed.…”

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confidence: 99%

“…18 Previous reports on enantioselectivity of thalidomide and analogues such as N-(2′,6′-dioxopiperiden-3′-yl)phthalimidine are questionable, since preparations of unstable enantiomers, e.g., nonmethylated chiral carbon, racemized in vitro and in vivo. 14 Heger et al suggested that preparations of derivatives locked in each optical configuration would be required to confirm selective effects of optical isomers of thalidomide analogues. 16 We report here the preparation and purification of 10a and 10b, which are the stabilized enantiomers of 5c.…”

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confidence: 99%

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Synthesis and Enantiomeric Separation of 2-Phthalimidino-glutaric Acid Analogues: Potent Inhibitors of Tumor Metastasis

et al. 1999

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Synthesis and Enantiomeric Separation of 2-Phthalimidino-glutaric Acid Analogues: Potent Inhibitors of Tumor Metastasis

et al. 1999

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“…Knoche et al [51] reported the racemization of thalidomide in phosphate buffer of pH 7.4 at 37°C temperatures. 2-Phthalimidinoglutarimide and 2-phthalimidoadipinimide (derivatives of thalidomide) showed rapid racemization [52,53]. Nunes et al [54] described the epimerization reaction of pilocarpine (2S:3R) at C-2 chiral atom at pH 7.4 and 35°C with half life of 36 days.…”

Section: In Vitro Racemizationmentioning

confidence: 98%

Homochiral Drug Design and Development by Racemization

Ali

2007

CCHTS

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One of the enantiomers of a racemic drug may be pharmacologically inactive or toxic or ballast and, hence, U.S. FDA and European agencies have issued certain guidelines for marketing of optically active (homochiral) drugs. However, some homochiral drug enantiomers racemize in to human body leading to the generation of other antipodes, which may be toxic or ballast to the human beings. In addition, racemization reduces the administrated dosage concentration when the optically active enantiomer is converted into its inactive form. Therefore, racemization studies of homochiral drugs are the important and urgent need of today. This article reviews in vitro and in vivo racemization of homochiral drugs. The racemization of some homochiral drugs is described considering the affect of different variables such as temperature, concentration of the drug, ionic concentration, pH, addition of cyclodextrins, formation of inclusion complexes, etc. Efforts have also been made to discuss the mechanisms of the racemization process. Attempts have been made to suggest safe dosages of such drugs.

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“…2-Phthalimidinoglutarimide and 2-phthalimidoadipinimide (derivatives of thalidomide) showed a rapid racemization. 59,60 Nunes et al 61 described the epimerization reaction of pilocarpine (2S:3R) at C-2 chiral atom at pH 7.4 and 358C with half life of 36 days. Pepper et al 62 reported in vitro racemization of aromatase inhibitors i.e.…”

Section: In Vitro Racemizationmentioning

confidence: 99%

Role of racemization in optically active drugs development

et al. 2007

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U.S. Food and Drug Administration issues certain guidelines for marketing of optically active drugs as some enantiomers racemize into human body, leading to the generation of other antipodes, which may be toxic or ballast to the human beings. Moreover, racemization reduces the administrated dosage concentration as optically active enantiomer converted into its inactive counter part. Therefore, the study of racemization of such type of drugs is an important and urgent need of today. This article describes in vitro and in vivo racemization of optically active drugs. The racemization process of various optically active drugs has been discussed considering the effect of different variables i.e. pH, temperature, concentration of the drug, ionic concentration, etc. Attempts have also been made to discuss the mechanisms of racemization. Besides, efforts have been made to suggest the safe dosages of such type of drugs too.

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The enantiomers of the teratogenic thalidomide analogue EM 12

Cited by 31 publications

References 9 publications

Synthesis and Enantiomeric Separation of 2-Phthalimidino-glutaric Acid Analogues: Potent Inhibitors of Tumor Metastasis

Synthesis and Enantiomeric Separation of 2-Phthalimidino-glutaric Acid Analogues: Potent Inhibitors of Tumor Metastasis

Homochiral Drug Design and Development by Racemization

Role of racemization in optically active drugs development

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