[Synthesis and teratogenic action of n-hydroxythalidomide].
N-Hydroxythalidomide (1d), a potential metabolite of thalidomide (1a), was synthesized from N-phthalyglutaminic acid anhydride (1b) and O-tetrahydropyraline hydroxylamine, followed by deprotection. The teratogenicity of 1d was studied using the Hen's-Egg-Test model which had been found applicable for 1a. 1d was more teratogenic to chicken embryos compared to 1a. The percentage of teratogenic malformations in the 1d groups was 28-46%, whereas the percentage in the 1a groups was 20-23%. The oxygen protected precursor N-hydroxythalidomide (1c) was less teratogenic (11-15%).
Institu für Pharmazeutische Chemie Toxikologie der Westfálischen Wilhelms-Universität Münster.
G
G
Blaschke
H R
HR
Hess
N P
NP
Lüpke
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D002642:Chick Embryo; D013723:Teratogens; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000633:toxicity
D013723:Teratogens; C060554:N-hydroxythalidomide; D013792:Thalidomide
Synthese und teratogene Wirkung von N-Hydroxy-thalidomid.