Hydantoin activity

A series of 29 3-alkyl 5-arylimidazolidinones, or hydantoins, active at the CBi receptor has been published by Kanyonyo et al. [344] with a subsequent publication describing the relationship between the experimentally derived lipophilicity and proposed modes of binding for non-polar and polar hydantoins derivatives [345] (Table 6.49). 

Reactions at G-5. The C-5 atom of hydantoins can be considered as an active methylene group, and therefore is a suitable position for base-cataly2ed condensation reactions with aldehydes (44). 2-Thiohydantoins give the reaction more readily than their oxygen counterparts ... 

Hydantocidin. Hydantocidin (182), C2H2QN2O3, is elaborated by S. hygroscopicus (278). It is unique in that the anomeric carbon of the ribosyl moiety forms the spHo bond of hydantoin (279). The ribofuranose moiety which has been reported to be in a Q -endo conformation (279) has been synthesized (280,281). Hydantocidin is a herbicidal nucleoside with activity against monocotyledenous and dicotyledenous plants. 

Many hydantoins are endowed with significant pharmacological activities as highlighted by 5,5-diphenylhydantoin (Dilantin ), an anticonvulsant and antiepileptic discovered by Parke-Davis in 1940 s. Despite the lapse of more than half a century, Dilantin still plays an important rote in modem medicine. Meanwhile, another anticonvulsant 15 was synthesized from 9,10-dimethoxy-l,3,4,6,7,llb-hexahydro-pyrido[2,l-a]isoquinolin-2-one (14) under the standard Bucherer-Lieb variation in a 2 1 water-ethanol solution (15a 15b = 8 l). ... 

The hydantoin moiety has been utilized as a biostere for the peptide linkage, transforming a peptide lead into an orally available drug candidate. Therefore, an Arg-Gly-Asp-Ser tetrapeptide (18) lead structure was modified to a non-peptide RGD mimetic as an orally active fibrinogen receptor antagonist 19. ° ... 

Furthermore, pharmacological active hydantoins 23-26 have been synthesized... 

As we have seen previously, succinimides containing a quaternary carbon form the basis for a series of anticonvulsant drugs. In the course of research in this series, it was found that the inclusion of additional hetero atoms in the ring was quite compatible with anticonvulsive activity. We consider here the oxa-zolidinediones a discussion of the hydantoins is found later in this section. 

Mn2(CO)io in a simple photoinitiated free radical polymerization. The antiplatelet activity of these polymers were compared with that of poly(ether-Wrethane) carrying the hydantoin residues in side chains. 

DMDM HYDANTOIN Typical use concentrations 0.15 -0.4% Cheap Water soluble Low oil solubility Broad spectrum of activity Active at low concentrations Active between pH 4 -10 Non-volatile Good heat stability Formaldehyde donor... 

Hydantoins are well-known anticonvulsant agents and as such have found extensive use in the treatment of epilepsy. Replacement of one of the carbonyl groups by thiocarbonyl is consistent with anticonvulsant activity. Thus, condensation of the ethyl ester... 

In an attempt to form orally active penicillins unrelated to ampicillin, use was made of the fact that certain spiro a-aminoacids, such as 9, are well absorbed orally and transported like normal amino acids. Reaction of cyclohexanone with ammonium carbonate and KCN under the conditions of the Bucherer-Bergs reaction led to hydantoin 10. On acid hydrolysis, a-amino acid 11 resulted. Treatment with phosgene... 

Lopez-Rodriguez, M.L., Rosado, M.L., Benhamu, B., Morcillo, M.J., Fernandez, E. and Schaper, K.-J. (1997) Synthesis and structure-activity relationships of a new model of arylpiperazines. 2. Three-dimensional quantitative structure-activity relationships of new hydantoin-phenylpiperazine derivatives with affinity for 5-HTIA and oq receptors. A comparison of CoMFA models. Journal of Medicinal Chemistry, 40, 1648-1656. 

FIGURE 7.34 Decomposition of the symmetrical anhydride of A-methoxycarbonyl-valine (R1 = CH3) in basic media.2 (A) The anhydride is in equilibrium with the acid anion and the 2-alkoxy-5(4//)-oxazolone. (B) The anhydride undergoes intramolecular acyl transfer to the urethane nitrogen, producing thelV.AT-fcwmethoxycarbonyldipeptide. (A) and (B) are initiated by proton abstraction. Double insertion of glycine can be explained by aminolysis of the AA -diprotected peptide that is activated by conversion to anhydride Moc-Gly-(Moc)Gly-0-Gly-Moc by reaction with the oxazolone. (C) The A,A -diacylated peptide eventually cyclizes to the IV.AT-disubstituted hydantoin as it ejects methoxy anion or (D) releases methoxycarbonyl from the peptide bond leading to formation of the -substituted dipeptide ester. 

Hydantoin analogs in this series 72) were prepared. Most of these compounds, however, were found less active as anticonvulsants than the corresponding phenyl derivatives. Only a few were found to have the same order of activity as 5,5-diphenylhydantoin. 

It has been shown recently that papain exhibits hydantoinase activity. This enzyme of plant origin hydrolyzes not only 5-monosubstituted but also 5,5-disubstituted hydantoins to the corresponding N-carbamoylamino acids. Since chemical hydrolysis of the latter yields the corresponding amino acids, this approach may be of interest in amino acid synthesis [145],... 

Answer D. Phenyl hydantoins decrease the activity of vitamin K, which is required for the y-carboxylation of coagulation factors (11, VII, IX, X), as well as proteins C and S. 

The mechanism of action of hydantoins is not yet conclusive. According to one hypothesis, hydantoins prevent high-frequency activation of the epileptogenic center and also facilitate secretion of sodium ions, which reduces excitation of neurons and prevents then-activation upon contact with impulses from the epileptogenic center. 

Drugs that may affect APAP include barbiturates, carbamazepine, hydantoins, isoniazid, rifampin, sulfinpyrazone, ethyl alcohol, and activated charcoal. 

---