Hydantoin derivatives

Table 1. Melting Points of Some Hydantoin Derivatives ...

Hydantoin derivatives show weak absorption in the uv-visible region, unless a part of the molecule other than the imidazohdinedione ring behaves as a chromophore (13) however, piC values have been determined by spectrophotometry in favorable cases (14). Absorption of uvby thiohydantoins is more intense, and the two bands observed have been attributed to n — tt and n — tr transitions of the thiocarbonyl group (15,16). Several piC values of thiohydantoins have been determined by uv-visible spectrophotometry (16). 

H-nmr chemical shifts of N-1—H and N-3—H signals have been used as a criterion for distinguishing between N-l-substituted and N-3-substituted hydantoin derivatives (22). They can often be related to electronic properties, and thus good linear correlations have been found between the shifts of N—H and Hammett parameters of the substituents attached to the aryl group of 5-arylmethylenehydantoins (23). 

C-nmr data have been recorded and assigned for a great number of hydantoin derivatives (24). As in the case of H-nmr, useful correlations between chemical shifts and electronic parameters have been found. For example, Hammett constants of substituents in the aromatic portion of the molecule correlate weU to chemical shifts of C-5 and C-a in 5-arylmethylenehydantoins (23). Comparison between C-nmr spectra of hydantoins and those of their conjugate bases has been used for the calculation of their piC values (12,25). N-nmr spectra of hydantoins and their thio analogues have been studied (26). The N -nmr chemical shifts show a linear correlation with the frequencies of the N—H stretching vibrations in the infrared spectra. 

Miscellaneous Reactions. Some hydantoin derivatives can serve as precursors of carbonium—immonium electrophiles (57). 5-Alkoxyhydantoins are useful precursors of dienophiles (17), which undergo Diels-Alder cycloadditions under thermal conditions or in the presence of acid catalysis (58). The pyridine ring of Streptonigrine has been constmcted on the basis of this reaction (59). 

Adding amines to coating compounds containing other polymers of hydantoin derivatives permits thermal curing of the coating compounds, which are useful as electrical insulators of wires under a broad range of conditions without loss of coating flexibiUty (101). 

In a German patent issued in 1929, Bergs described a synthesis of some 5-substituted hydantoins by treatment of aldehydes or ketones (1) with potassium cyanide, ammonium carbonate, and carbon dioxide under several atmospheres of pressure at 80°C. In 1934, Bucherer et al. isolated a hydantoin derivative as a by-product in their preparation of cyanohydrin from cyclohexanone. They subsequently discovered that hydantoins could also be formed from the reaction of cyanohydrins (e.g. 3) and ammonium carbonate at room temperature or 60-70°C either in water or in benzene. The use of carbon dioxide under pressure was not necessary for the reaction to take place. Bucherer and Lieb later found that the reaction proceeded in 50% aqueous ethanol in excellent yields for ketones and good yields for aldehydes. ... 

Dantrolene is the mainstay of MH treatment. It has long been available for the treatment of muscle spasm in cerebral palsy and similar diseases. It is a hydantoin derivative that was first synthesized in 1967, and reported to be effective in the treatment of porcine MH in 1975. Also in 1975, dantrolene was shown to be more effective than procainamide in the treatment of human MH, which until that time was the drug of choice. However, the intravenous preparation was not made available until November 1979. It significantly lowered mortality. The half-life of dantrolene is estimated to be 6-8 hr. Dantrolene s primary mode of action is the reduction in calcium release by the sarcoplasmic reticulum. Dantrolene also exerts a primary antiarrhythmic effect by increasing atrial and ventricular refractory periods. Side effects of dentrolene include hepatotoxicity, muscle weakness, ataxia, blurred vision, slurred speech, nausea, and vomiting. Dantrolene is not contraindicated in pregnancy, but it does cross into breast milk and its effect on the neonate is unknown. 

The silylated glycine derivative 1450 cyclizes spontaneously on heating to 85-140 °C to give the hydantoin derivative 1451 in 94% yield [20, 21]. The silylated hy-dantoin 1453 is obtained by reacting silylated N-carboxymethylglycine 1452 with trimethylsilyl isocyanate 327 and subsequent heating to 140°C [22] (Scheme 9.12). 

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). 

The treatment of hydantoin derivatives (1293) with alkali metal hydroxide in boiling aqueous ethanol for 1 -2 hr gave orotic acid derivatives (1294) in good yields (82EUP52341). 

L-Serine methyl ester can be transformed into methyl oxazolidin-2-one-3-carboxylate with phosgene and aqueous potassium carbonate (90TL7407). Some AAs (Gly, Val, Phe) were transformed into their iV-(2-chloroethylcar-bamoyl) derivatives, and these can cyclize into oxazolines (Scheme 24) (83T2255). In boiling water they are transformed into hydantoin derivatives. 

Syldatk, C., Laufer, A., Muller, R. and Hobe, H. (1990) Prodnction of optically pure D and L-df-amino acids by bioconversion of D,L-5-monosnbstituted hydantoin derivatives. Advances in Biochemical Engineering, 41, 28-75. 

Antiseizure heterocyclic ring structure. The X varies as follows hydantoin derivatives, -N- barbiturates, -C-N- oxazolidinediones, -0- succinimides, -C-acetylureas, -NH2 (N connected to C2). Ri, R2/ and R3 vary within each subgroup. 

Kim80 reported recently a convenient synthesis of hydantoin derivatives (41) by PTC-catalyzed nucleophilic substitution, followed by cyclization. 

Several 3-vinyl- and 1,3-divinyl-hydantoin derivatives have been prepared and converted to polymers having pendant hydantoin groups, e.g. (66) (B-74MI11100). Interesting spiro hydantoin polymers (67) are readily prepared from the very reactive 5-methylenehydantoin, hydrolysis of which cleanly produces polymers containing a-aminoacrylic acid units and having corresponding polyampholytic properties. 

Tertiary amines were amongst the first initiators of NCA polymerisation which had been described in the literature and it seems that the polymerisation of all the known NCA s may be accomplished by their action. Wessely (77) reported in 1925 that glycine and phenyl alanine NCA s are readily polymerised in pyridine at ambient temperatures, and in the following paper (72) he reported a similar polymerisation of sarcosine NCA. The polypeptides produced by this initiator apparently formed cyclic polymers since no terminal end groups could be detected 41). It is significant that appreciable quantities (a few %) ot 3-acetic-hydantoin derivatives were found in the polymers formed from glycine and phenyl alanine NCA s but none was detected in the polymerised sarcosine NCA (72). This evidence suggests that the mechanisms of polymerisation initiated by aprotic bases may be different for the non-N-substituted NCA and the N-substituded anhydrides. 

The most common method of HOBr generation today is probably by dissolution of various types and sizes of hydantoin derivative granules, sticks, and tablets. The tablets especially have proved to be popular, despite their cost premium of around 20% over granules. 

The dCyd oxidation products 5-hydroxy-dCyd and 5-hydoxy-dUrd have low oxidation potentials (Wagner et al. 2004) and are hence likely to be oxidized further. For this reason the oxidation of 4-hydroxy-dUrd has been studied (Riviere et al. 2004). Using Br2 or Na2IrBr6 but also menadione plus UV as oxidants, the main oxidation products were the isodialuric acid, dialuric acid and hydantoin derivatives. 

Dantrolene, a hydantoin derivative, reduces the contraction of skeletal muscle, acting directly on the muscle and not at the neuromuscular junction. It is thought to reduce the amount of calcium released and hence prevent excitation-contraction coupling (Figure 26.4). Its usefulness in the treatment of anesthetic-induced malignant hyperthermia may be due to its calcium-related uncoupling actions. 

The synthesis of N-(conversion into 3-spiro-5-hydantoin derivatives (31) have been described.15... 

Dantrolene is a hydantoin derivative related to phenytoin that has a unique mechanism of spasmolytic activity. In contrast to the centrally active drugs, dantrolene reduces skeletal muscle strength by interfering with excitation-contraction coupling in the muscle fibers. The normal contractile response involves release of calcium from its stores in the sarcoplasmic reticulum (see Figures 13-1 and 27-10). This activator calcium brings about the tension-generating interaction of actin with myosin. Calcium is released from the sarcoplasmic reticulum via a calcium channel, sometimes called the ryanodine receptor channel because the plant alkaloid ryanodine combines with a receptor on the channel protein and, in the case of the skeletal muscle channel, locks it in the open position. 

Payen O, Top S, Vessieres A, Brule E, Plamont M, McGlinchey M, Muller-Bunz H, Jaouen G (2008) Synthesis and structure-activity relationships of the first ferrocenyl-aryl-hydantoin derivatives of the nonsteroidal antiandrogen nilutamide. J Med Chem 51 1791-1799... 

Title Hydantoin Derivatives with Affinity for Somatostatin Receptors D. Berney et al., US Patent 7,019,004 (March 28, 2006)... 

Imidazole reacts very slowly with singlet oxygen to form the imida-zolidone (86)42S through an elimination reaction involving proton loss and cleavage of the oxygen-oxygen bond of the transannular peroxide (87). On the other hand, 4-phenylimidazole forms a hydantoin derivative (88) and V-benzoyl-V -methoxycarbonylurea (89). This... 

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