Kang-Chien Liu

Bio: Kang-Chien Liu is an academic researcher from National Defense Medical Center. The author has contributed to research in topic(s): Thiazole & Benzothiadiazine. The author has an hindex of 10, co-authored 39 publication(s) receiving 258 citation(s).

Synthese und Bioaktivitäten einiger 2‐Oxo‐naphtho[1,2‐d]thiazolo‐[3,2‐a]pyrimidin‐Derivate

Abstract: Zur Untersuchung der Struktur-Wirkungs-Beziehungen von Substanzen der Naphtho[1,2-d]thiazolo[3,2-a]pyrimidin-Reihe wurden die Titel-Verbindungen 5a–d zusatzlich zu den fruher beschriebenen 2-Oxo-Derivaten dargestellt. Die Darstellung erfolgte durch nucleophilen Angriff von 2-Aminonaphtho[1,2-d]thiazol (2) auf die entsprechenden β-Keto-Ester 3a–d. Die Produkte zeigten anders als die 2-Oxo-Derivate keine hypotensive Wirkung an normotensiven Ratten. Jedoch zeigten sie eine bemerkenswerte diuretische Aktivitat nach p.o. Verabreichung von 10–30 mg/kg bei den gleichen Tieren. Die Wirkung dauerte in den meisten Fallen mehr als funf Stunden. Synthesis and Bioactivities of Some Derivatives of Naphtho[1,2-d]thiazolo[3,2-a]pyrimidin-4-one In continuing the study of the structure-activity relationships of compounds of the naphtho[1,2-d]thiazolo[3,2-a]pyrimidine series, the 4-oxo derivatives 5a–d were synthesized in addition to the 2-oxo compounds reported previously. The synthesis was accomplished by nucleophilic attack of 2-aminonaphtho[1,2-d]thiazole (2) on the corresponding β-keto esters 3a–d. Unlike the 2-oxo derivatives, the products showed no hypotensive effect on normotensive rats. However, all compounds exhibited a pronounced diuretic activity in the same animals after oral administration of 10–30 mg/kg. The activity persisted in most cases for more than five hours.

Studies on quinazolinones. 2. Synthesis of 2-(4-benzylpiperazin-1-ylmethyl)-2,3-dihydro-5H-oxazolo[2,3–6]quinazolin-5-one and -2,3-dihydro-5H-thiazolo[2,3-b]quinazolin-5-one†

Abstract: To search for novel antihypertensive heterocycles in the condensed quinazoline series, two representative compounds were synthesized via a suitable reaction sequences. Treating anthranilonitrile with allyl isocyanate gave 2-(allylureido)benzonitrile (10) in a quantitative yield. Compound 10 was cyclized to 3-allylquinazoline-2(1H, 4(3H)-dione (11). Bromination of 11 in carbon tetrachloride converted it into the corresponding 3-(2,3-dibromopropyl) derivative (12) in 92% yield. Ring closure of 12 was effected by the action of alkali to afford 2-bromomethyl-2,3-dihydro-5H-oxazolo[2,3-b]quinazolin-5-one (13). The title compound, 2-(4-benzylpiperazin-1-ylmethyl)-2,3-dihydro-5H-oxazolo[2,3-b]quinazolin-5-one (7) could be obtained by a reaction of either 12 or 13 with 1-benzylpiperazine respectively. Starting from the readily available 3-allyl-2H-thioxoquinazolin-4(3H)-one (16) via the analogous reactions gave the 2-bromomethyl-2,3-dihydro-5H-thiazolo[2,3-b]-quinazolin-5-one (19) in good yield. However, the reaction of 19 with 1-benzylpiperazine provided another target compound, 2-(4-benzylpiperazin-1-ylmethyl)-2,3-dihydro-5H-thiazolo[2,3-b]quinazolin-5-one (8) only in poor yield (8%). As major product, the dehydrobrominated compound, 2-methylene-2,3-dihydro-5H-thiazolo[2,3-b]quinazolin-5-one (22) was isolated. A preliminary pharmacological evaluation revealed that both compounds 7 and 8 are devoid of the antihypertensive activity.

Cyclocondensation of 3-amino-2-iminonaphtho[1,2-d]-thiazole with α-ketocarboxylic acid derivatives: Synthesis of 2-substituted 3-Oxo-3H-naphtho[1′,2′:4,5]thiazolo-[3,2-b][1,2,4]triazines as potential anti-HIV agents

Abstract: The cyclocondensation of 3-amino-2-iminonaphtho[1,2-d]thiazole (1) with a series of α-keto mono- and dicarboxylic acid derivatives 5a-i under different conditions was investigated. When the experiments were performed by refluxing in glacial acetic acid, the corresponding cyclized products, 2-substituted 3-oxo-3H-naphtho[1′,2′:4,5]thiazolo[3,2-b][1,2,4]triazines 4 were obtained in fair to good yields. On the other hand, when the reaction was conducted in boiling ethanol, it gave only the open chain condensates 6, or in rare cases, together with minor amount of 4. Since the intermediates 6 exist as mixture of both E- and Z-isomers, cyclization through heating was found insufficient. In any event representative compounds 4b,g,i have been evaluated for anti-HIV activity, but none of them were active.

Reactions of 2-aminothiobenzamide with isocyanates: A new synthesis of 2, 3-dihydroimidazo[1, 2-c]quinazolin-5(6H)-one and 3, 4-Dihydro-2H-pyrimido[1, 2-c]quinazolin-6(7H)-one

Abstract: 2-(2-Chloroethylureido)- and 2-(3-chloropropylureido)thiobenzamides 5a, b were prepared in good yields by treating 2-aminothiobenzamide with 2-chloroethyl and 3-chloropropyl isocyanates respectively. Subsequent treatment of compound 5a and 5b either with alkali or mineral acid led to the formation of 2, 3-dihydro-imidazo[1, 2-c]quinazolin-5(6H)-one 7a and 3, 4-Dihydro-2H-pyrimido[1, 2-c]quinazolin-6(7H)-one 7b.

Synthesis and reactions of “biginelli‐compounds”. Part I

Abstract: Various reactions of 2-oxo(or thioxo)-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid derivatives (Biginelli-compounds) were investigated. The site of methylation and acylation on 6-methyl-4-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid ethyl ester 1a and its 2-oxo derivative 9a was studied. The synthesis of pyrimido[2,3-b]thiazines and thiazolo[3,2-a]pyrimidines was accomplished by condensation of 1a with 1,3-and 1,2-dielectrophiles. A Dimroth-like rearrangement yielding 6H-1,3-thiazines can be observed when 1a was treated with dimethylformamide and phosphorus oxychloride. The formation of indeno[1,2-d]pyrimidines can be achieved by intramolecular Friedl-Crafts acylation of 9a and 13, respectively. Finally a route for the preparation of 4,6-disubstituted-pyrimidine-5-carbonitriles is presented, starting with Biginelli-compound 25.

Preparation of amines

Abstract: A process for the preparatiion of an amine which comprises reacting a primary or secondary alcohol and a nitrogen compound selected from the group consisting of ammonia and primary and secondary amines, at temperatures of from 80° to 250° C and pressures of from 1 to 400 bar using hydrogen in the presence of a zirconium/copper/nickel catalyst, wherein the catalytically active material contains from 20 to 85 wt % of oxygen-containing zirconium compounds, calculated as ZrO 2 , from 1 to 30 wt % of oxygen-containing compounds of copper, calculated as CuO, from 30 to 70 wt % of oxygen-containing compounds of nickel, calculated as NiO, from 01 to 5 wt % of oxygen-containing compounds of molybdenum, calculated as MoO 3 and from 0 to 10 wt % of oxygen-containing compounds of aluminum and/or manganese, calculated as Al 2 O 3 or MnO 2 , respectively

New methodology for the preparation of quinazoline derivatives via tandem aza-Wittig/heterocumulene-mediated annulation. Synthesis of 4(3H)-quinazolinones, benzimidazo[1,2-c]quinazolines, quinazolino[3,2-a]quinazolines and benzothiazolo[3,2-c]quinazolines

Abstract: The aza-Wittig reaction of iminophosphoranes derived from N-substituted o-azidobenzamides, 2-(o-azidophenyl)-benzimidazole, -benzothiazole or -3,1-benzoxazin-4-one with heterocumulenes leads to functionalized quinazolines. Iminophosphoranes 9 , derived from N-substituted o-azidobenzamides, react under mild conditions with isocyanates to form 4H-3,1-benzoxazine-4-imines 11 which are converted into 2-substituted-4(3H)-quinazolinones 12 . Iminophosphoranes 9 also react with carbon disulfide and carbon dioxide to give the quinazolinones 13 and 14 respectively. Iminophosphorane 26 , derived from 2-(o-azidophenyl)benzimidazole, reacts with isocyanates, carbon disulfide and carbon dioxide to form 6-substituted benzimidazo[1,2-c]quinazolines 27, 28 and 29 respectively. In benzene at room temperature, iminophosphorane 31 , reacts with isocyanates yielding quinazolino[3,2-a]quinazolines 34 . Compounds 34 can also be prepared from iminophosphorane 36 and isocyanates. Iminophosphorane 40 derived from 2-(o-azidophenyl)benzothiazole reacts with aliphatic and aromatic isocyanates or isothiocyanates to give 7H-benzothiazolo[3,2-c]quinazoline-7-imines 42 . Iminophosphorane 40 also reacts with carbon dioxide or carbon disulfide to afford the corresponding isocyanate 43 or isothiocyanate 44 . The molecular structures of 11d and 42a have been determined by X-ray diffraction methods.

Molecular modeling study and synthesis of novel pyrrolo[2,3-d]pyrimidines and pyrrolotriazolopyrimidines of expected antitumor and radioprotective activities.

Abstract: Novel pyrrolo[2,3-d]pyrimidine derivatives 4a–e, 10, 14, 15, pyrazolopyrrolopyrimidine 13, pyrrolotriazolopyrimidine 5–9, 17 and pyrrolopyrimidotriazine 18 are reported herein. The design of these compounds was based upon the molecular modeling simulation of the fitting values and conformational energy values of the best-fitted conformers to VEGFRTK inhibitor hypothesis. This hypothesis was generated from its corresponding lead compounds using CATALYST software. The structures of these compounds were confirmed by microanalyses, IR, 1H NMR, and mass spectral data. Compounds 6 and 15 showed interesting in vitro antitumor activity compared to doxorubicin as positive control. These results are nearly consistent with the molecular modeling studies. Docking studies were made on compound 15 to predict its binding mode. Moreover, compound 10 exhibited a significant radioprotective activity.