Nau, Heinz published the artcileWeak acids may act as teratogens by accumulating in the basic milieu of the early mammalian embryo, Quality Control of 16332-06-2, the publication is Nature (London, United Kingdom) (1986), 323(6085), 276-8, database is CAplus and MEDLINE.
Among the 11 drugs or chems. which are well-documented human teratogens, 8 (or their main metabolites) are weak acids whereas none is a weak base. Moreover, 23 out of 32 acids tested were teratogenic in at least 1 animal species. The acidic property of drugs may therefore be an important determinant of teratogenicity. The intracellular pH (pHi) of the mouse and rat embryo is higher than that of maternal plasma, as determined by the relative accumulation of dimethadione [695-53-4]. The antiepileptic drug valproic acid [99-66-1] and its pharmacol. active unsaturated metabolite accumulate in embryonic tissue to higher concentrations than in maternal plasma, whereas the essentially neutral amide of valproic acid (valpromide [2430-27-5]) or ethosuximide [77-67-8] do not accumulate in the embryo; in the rat the pHi of the embryo decreases with advancing gestation; in general agreement with the pH partiton hypothesis, the exposure of the embryo to valproic acid also decreases significantly during that period. Furthermore, the amides of 2 weak acid teratogens, valpromide and methoxyacetamide [16332-06-2], and ethosuximide, are much less teratogenic than their acid counterparts. Thus, weakly acidic drugs, by virtue of their physicochem. nature, accumulate in the early embryo with its relatively high pHi.
Nature (London, United Kingdom) published new progress about 16332-06-2. 16332-06-2 belongs to ethers-buliding-blocks, auxiliary class Amine,Aliphatic hydrocarbon chain,Amide,Ether, name is 2-Methoxyacetamide, and the molecular formula is C3H7NO2, Quality Control of 16332-06-2.
Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem