• 약학회지
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• 제48권2호
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• pp.141-146
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• 2004

Selective COX-2 inhibitors were expected to retain anti-inflammatory activity by inhibition of prostaglandin production with reduction of gastric and renal side effect associated with non-steroidal anti-inflammatory drugs. This study reported the syntheses of novel 2-thiohydantoin and hydantoin derivatives which have the structure of 5-membered heterocyclic ring substituted with two aryl groups, phenyl group at 5-position and p-sulfamylphenyl or p-methoxyphenyl group at 1-position. These synthetic compounds showed significant COX-2 activities in vitro screening. Among them, 5-phenyl-2-thiohydantoin and hydantoin substituted with benzyl group at 3-position, compounds 5 and 8, could be considered as lead compounds with $IC_{50}$/=13.13∼18.78 $\mu\textrm{g}$/$m\ell$ for the development of COX-2 inhibitors.

• Bulletin of the Korean Chemical Society
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• 제35권12호
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• pp.3609-3617
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• 2014

A series of compounds containing both 1,3,4-oxadiazole and thiohydantoin were synthesized as a promising scaffold for application in medicinal chemistry. The key step of the synthesis is a microwave-assisted cyclization of semicarbazides possessing a thiohydantoin moiety at one of the acyl termini using $POCl_3$ as a dehydrating reagent. A wide range of semicarbazides were prepared through the substitution of hydrazides with an N-acylated thiohydantoin derived from the cyclization of the corresponding isothiocyanate with an amino acid and subsequent N-acylation of the resultant thiohydrantion. Consequently, the 58 number of 1,3,4-oxadiazole derivatives having a thiohydantoin substituent were prepared in good overall yields.

• 대한화학회지
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• 제55권3호
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• pp.412-417
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• 2011

[$M_2L(NO_3)_n(H_2O)_m$]의 일반식을 갖는 일련의 동종이핵 착물을 합성하여 원소분석, 열분석, 몰 전기전도도, 자기모멘트 및 분광학적 방법(IR, UV-vis 및 $^1H$-NMR)을 통해 특성을 조사하였다. 이 경우, 일반식에 있어서 M=$UO_2$(VI), ZrO(IV), Th(IV); L=3-benzylidine-imino-5-p-sulphonamido phenyl azo-2-thiohyatoin(bispt), 3-furfurylidine-imino-5-psulphonamido phenyl azo-2-thiohydantoin(fispt),3-pyridyl-2'-methylene-imino-5-p-sulphonamido phenyl azo-2-thiohydantoin (pmispt) 및 3-thienyl-2'-methylene-imino-5-p-sulphoanamido phenyl azo-2-thiohydantoin(tmispt); Th(IV)에 대해서 n=8 그 외의 것에 대해서는 n=4, bispt에 대해서는 m=4 그 외의 것에 대해서는 m=3을 의미한다. 이러한 결과에서 얻은 정보를 통해 리간드들은 4배위를 하는 것으로 확인되었는데, 즉 한 중심금속은azomethine 질소 및 카르보닐 산소에 배위되는 반면, 또 다른 중심금속은 아조 질소 및 thioimido 질소에 배위되어 위의 조성을 갖는 동종이핵 착물을 이룬다. 몇 가지 병원균에 대한 리간드와 그들의 지르코닐 착물의 독성 연구도 수행하였다.

• 한국식품영양과학회지
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• 제3권1호
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• pp.69-76
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• 1974

The method of amino acid sequence determination from the C-terminal amino acid is proposed and mass spectrometric identification of thiohydantoins described previously. In this paper was discussed the fragmentation of thiohydantoin-ring by deutero substitution and model tripeptide have been degraded through three stages each, with interpretable results. The conditions employed in this method are mild enough for biological materials. The main features of the method are the following. 1. Thiohydantoins were formed in a non-aqueous medium a mixture of acetic anhydride, acetic acid and ammonium thiocyanate. 2. Mass sepectra of thiohydantoins derived from 20 amino acids were obtained with a mass spectrometer, JEOL model JMS-06H. 3. Cleavage of peptidyl thiohydantoin was made with an acidic from of a cation-exchange resin. (Amberlite IR-120) 4. Separation of the cleaved thiohydantoin and the parent peptide less one amino acid moiety was made by chromatography on a Sephadex G-10 column. 5. The peptide fraction was concentrated by freezedrying. 6. Thiohydantoin derivative of carboxyl terminal amino acid residue was introduced with a direct inlet probe in methanol solution.

• 약학회지
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• 제32권2호
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• pp.112-116
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• 1988

The resolution of N-trifluoroacetyl (N-TFA) ter-isopropylesters of Ala, Ile, Leu, Val and Phe by gas chromatography on the (S)-5-isobutyl-$N^3$-phenyl-2-thiohydantoin as stationary phase was investigated. The phase was employed at several column temperatures $(140^{\circ}C{\sim}200^{\circ}C)$ and the separation factors were $1.18{\sim}1.45$ range for five amino acid enantiomers. The possible mechanism of chiral recognition was investigated by NMR technique and the association constant$(K_c)$ was calculated as 201.3(r=0.98) for alanyl derivative.

• 한국식품영양과학회지
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• 제3권1호
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• pp.53-68
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• 1974

The thiohydantoin derivative derived from amino acid was used for the stepwise sequence analysis of peptide or protein from the carboxyl termini. Recently, SUZUKI reported the mass spectrometric identification about a part of these compounds. In this paper, was described the mass spectrometric identification of thiohydantoins derived from 20 amino acids. Mass spectra were obtained with a mass spectrometer, JEOL model JMS-06H and samples were introduced with a direct inlet probe. The molecular ion peaks and fragment ion peaks were identified easily, because these peaks appeared differently every amino acids and specially, it was easy discrimination between leucine and isoleucine. It is suggested that mass spectrometry was one of the useful methods to identify thiohydantoins derived from amino acids.

• 약학회지
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• 제48권2호
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• pp.135-140
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• 2004

For the development of new COX-2 inhibitors, 1,5-diarylhydantoins 5a∼5c and 1,5-diaryl-2-thiohydantoin 6a∼6c were synthesized from commercially available phenylacetic acids through esterification, bromination, C-N bond formation and cyclization. Esters 2a∼c were efficiently synthesized from the starting materials 1a∼c by refluxing in absolute methanol for 3 hours with catalytic concentrated sulfuric acid. Bromination of 2a∼c was carried out with use of N-bomosuccinimide at rt in dichloromethane. The bromine of 3a∼c was substituted with aniline in ethanol or N,N-dimethylformamide to provide 4a∼c. Hydantoins and 2-thiohydantoins were synthesized from 4a∼c by treatment of potassium isocyanate or potassium thiocyanate in dil-ethanol with triethylamine.

• 약학회지
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• 제32권3호
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• pp.170-176
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• 1988

The resolution of five amino acids derivatives by gas chromatography on phenylthiohydantoin derivatives as chiral stastionary phase was investigated. (S)-5-isopropyl, isobutyl, (sec)-butyl and benzoyl derivatives of $N^3-phenyl-2-thiohydantoin$ were synthesized from L-valine, L-leucine, L-isoleucine and L-phenylalanine, respectively. The phases were employed at several column temperatures ($140^{\circ}C{\sim}210^{\circ}C$). The separation factors were compared with each stationary phase with varying R groups. The possible mechanism of chiral recognition was investigated by NMR technique.

• Archives of Pharmacal Research
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• 제23권2호
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• pp.99-103
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• 2000

Acid and base catalyzed intramolecular cyclizations of N-benzoylthioureidoacetal, contain-ing four functional groups adjacent to thiourea such as benzocarbamoyl, acetal, thioure and amide, were investigated. The condensation reaction of N-benzoyl thiocarbamoylgly-cine amide in the presence of 10% aqueous NaOH provided 1-(2,2-dimethoxy)ethyl-imi- dazolidine-2-thione exclusively. In the presence of pyridine, it was transformed to 2- thiohydantoin. N-Benzoyl thiocarbamoyl glycine amide was completely transformed to an iminothiazolidine exclusively in the presence of Lewis acid such as borontrifluoride ether-ate or trimethylsilyl iodide. 1-(2,2-Dimethoxy)ethyl-imidazolidine-2-thione was transformed to imidazole[2,1-b]thiazole and pyrazino[5,1-a]imidazole in the presence of $BF_3$.$ET_2$O and formic acid, respectively.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.188.3-189
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• 2003

Nonsteriodal antiinflammatory drugs(NSAIDs) are widely used to treat pain, fever, and inflammatory conditions including osteoarthritis. But chronic patients suffer from gastrointestinal disturbances such as discomfort, nausea, peptic ulcer and severe bleeding because NSAIDs inhibit not only COX-2 associated with anti-inflammatory activity, but also COX-l accompanied with side effects in the stomach and kidney. Therefore, in this study, we designed a new 2-thiohydantoin derivatives as selective COX-2 inhibitors is that the 5-membered heterocycle ring is substituted with two aryl groups. (omitted)