Studies on antiatherosclerotic agents. Synthesis and inhibitory activities on platelet aggregation of 4-aryl derivatives of 7-ethoxycarbonyl-6,8-dimethyl-1 (2H)-phthalazinone.

4-Aryl derivatives of 7-ethoxycarbonyl-6,8-dimethyl-1(2H)-phthalazinone and related derivatives were newly synthesized in order to test for their inhibitory activities on platelet aggregation. 4-(2-Anisyl) compound and the corresponding 1-chloro derivative demonstrated significant activity.     

Synthesis of 3,4-Dihydrophthalazin-1(2H)-one by Zinc Reduction of Phthalazin-1(2H)-one

3,4-Dihydrophthalazin-1(2H)-one (II) was first prepared by H.Sund ¹⁾, by electrochemical reduction of phthalazin-1(2H)-one (I) (phthalazone). In the recent years we have described new syntheses of II, through easily hydrolyzable mono- or diacetyl- derivatives, namely condensation of 2-bromomethylbenzoylchloride with N,N'-diacetylhydrazine ²⁾ catalytic reduction of I in acetic acid ²⁾ or of 2-acetylphthalazone in acetic anhydride ³⁾ The reduction of I with zinc is known to proceed with ring contraction and formation of N-aminophthalimidine (III)⁴⁾ (zinc and sodium hydroxide at about 100[ddot]C) or of phthalimidine (IV) ⁵⁾ (zinc and hydrochloric acid under unspecified conditions).

Having observed that II is transformed into N-aminophthalimidine when heated with hydrazine hydrate ⁶⁾ or sodium hydroxide ²⁾, the zinc reduction of I was reinvestigated with the aim to find out in which cases the intermediate formation of II can be dem-onstratedo     

Synthesis of new (pyrazol-1-yl)(7-nitro-1h-indol-2-yl)ketone derivatives

The condensation of 7-nitroindole-2-carbohydrazide derivatives with acetylacetone lead to (pyrazol-1-yl)(7-nitroindol-2-yl)ketones.     

Synthesis and platelet aggregation inhibitory activities of 3-(2-oxopropylidene)azetidin-2-one derivatives. II.

A series of 3-acylidene-4-methylazetidin-2-one derivatives bearing various substituents at the 1-position of the azetidin-2-one ring was synthesized. These compounds were evaluated for platelet aggregation inhibitory activities. Most of the compounds synthesized showed potent inhibitory activities against rabbit platelet aggregation induced by adenosine diphosphate or collagen in vitro. Structure-activity relationships are also discussed.     

Design,synthesis and biological evaluation of 3,4-dihydronaphthalen-1(2H)-one derivatives as Bcl-2 inhibitors

Research on Chemical Intermediates - A series of new 3,4-dihydronaphthalen-1(2H)-one derivatives (6a–f) were designed, and synthesized by the Claisen–Schmidt condensation reaction....     

Synthesis of 3,4-dihydropyrimidin-2(1H)-one via Retro-Biginelli reaction

Hydrolytic behavior of 5-acetyl-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-one under alkaline condition has been explored. Mechanistic details are established by LCMS and HPLC. Evidence suggested that the deacetylative benzylidenation proceeds through the retro-Biginelli reaction. The scope of the retro-Biginelli reaction has been explored by the synthesis of substituted DHPs.     

1,3-Dipolar cycle-addition of 2-diazoalkanes to pyridazin-3(2H)-one derivatives. The formation of 3H-pyrazolo[3,4-d]pyridazin-4(5H)-one and 3H-pyrazolo[3,4-d]pyridazin-7(6H)-one derivatives

1,3-Dipolar cycloadditions of diazoalkanes to pyridazin-3(2H)-ones 1–7 and pyridazin-3(2H)-thiones 8 and 9 are regioselective producing 3H -pyrazolo[3,4-d]pyridazin-4(5H)-ones 15–19, 27–29 and 34–38 as the major products. In some instances, the isomeric 3H-pyrazolo[3,4-d]pyridazin-7(6H)-ones, such as 20 and 23 were isolated as the minor products. From 3 and 6 the primary 3a,7a-dihydro cycloadducts 25 and 26 , and rearranged 1,2-dihydro intermediate 31 were isolated. From 10 and 1-diazoindane the isomeric exo- and endospiro products 39 and 40 were formed.     

Synthesis of pyridin-2(1H)-one derivatives via enamine cyclization

The nucleophilic vinylic substitution reaction of the aliphatic enaminone 3-dimethylamino-2-formyl acrylonitrile 1 with the nucleophiles malononitrile and ethyl cyanoacetate produced the two unusual reaction adducts 3a and 3b in good to moderate yield under milder reaction conditions. Upon reaction with aromatic amines, these adducts yielded enamines 4 and 5, which eventually cyclized in the presence of base to produce the novel pyridin-2(1H)-one derivatives 8 and 9.     

One-pot,multi-component synthesis of 3,4-dihydropyrimidin-2(1H)-one derivatives containing ferrocenyl

Research on Chemical Intermediates - A novel series of 4-(substituted phenyl)-6-ferrocenyl-3,4-dihydropyrimidin- 2(1H)-ones has been synthesized by the Biginelli reaction between different...     

Pyrimidine derivatives. IX . Synthesis of bromosubstituted 5-nitro-2,4(1H,3H)-pyrimidinedione derivatives

The following 5-nitro-2,4(1H,3H)-pyrimidinediones possessing bromo substituted side chains at the 1- and 6-positions were prepared by bromination of 3,6-dimethyl-1-(ω-hydroxyalkyl)-5-nitro-2,4(1H,3H)-pyrimidinediones 4a and 4b and its nitrates 2a and 2b . The three of mono-bromo derivatives are: 1-(ω-acetoxyalkyl and ω-hydroxyalkyl)-6-bromomethyl-3-methyl. 6a, 6b, 7a and 7b and 1-(ω-bromoalkyl)-3,6-dimethyl-2,4(1H,3H)- pyrimidinediones 8a and 8b . The one type dibromo derivatives are: 1-(ω-bromoalkyl)-6-bromomethyl-3-methyl-2,4(1H,3H)-pyrimidinediones 5a and 5b .     

Synthesis of new 2-aryl-6-styryl-2,3-dihydropyridin-4(1H)-one derivatives from curcuminoids

Series of new 2-aryl-6-styryl-2,3-dihydropyridin-4(1H)-one derivatives were synthesized in acceptable to good yields by treatment of the curcuminoids with aqueous ammonia,the mechanism was proposed.By modification of the primary products,total 13 new compounds were obtained.The structures of all products were elucidated by spectroscopy analysis including HR-MS,~1H NMR and ~(13)C NMR.     

Biginelli 3,4-二氢嘧啶-2-酮衍生物的合成研究新进展

1893年, 意大利化学家Biginelli首次利用芳香醛、乙酰乙酸乙酯和尿素三组分“一锅煮法”合成了3,4-二氢嘧啶-2(1H)-酮. 此类化合物具有良好的生物活性和反应活性, 对近几年来有关Biginelli 3,4-二氢嘧啶-2(1H)-酮的衍生化反应、Biginelli不对称合成和Biginelli反应在天然产物合成中的应用研究进行了综述.     

A new 3,4-dihydronaphthalen-1(2H)-one from the leaves of Cinnamomum philippinense

Investigation of the leaves extract of Cinnamomum philippinense (Merr.) Chang (Lauraceae) led to the isolation of one novel compound, cinnamophilin D. Its structure was determined through in-depth spectroscopic and mass-spectrometric analyses.     

Synthesis and alkylation of 4,6-diphenyl-3-thiocarbamoyl-3,4,5,6-tetrahydropyridine-2(1H)-one and 4,6-diphenyl-3-thiocarbamoyl-3,4-dihydropyridine-2(1H)-one

Alkylation of 3-thiocarbamoyl-3,4,5,6-tetrahydropyridine-2(1H)-one with methyl iodide has given 5-methylthio-2,6-diazabicyclo[2.2.2]oct-5-en-3-one and 3-methyl-thiocarbonyl-3,4-dihydropyridine-2(1H)-one. Alkylation of 3-thiocarbamoyl-3,4-dihydridine-2(1H)-one with iodoacetamide affords 3-(1-amino-1-carbamoyl-3,4-methyl-thiomethylene)-1,4-dihydropyridine-2-one, which in acidic media is converted into 3-(4-oxo-3,5-dihydro-1,3-thiazol-2-ylidene)-1,4-dihydropyridine-2-one.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 787–794, June, 1989.     

Pyridazines. XV. Synthesis of 6-aryl-5-amino-3(2H)-pyridazinones as potential platelet aggregation inhibitors

Several 3(2H)-pyridazinones with amino groups at the 5-position of the pyridazine nucleus have been prepared. The 6-aryl-5-halo-3(2H)-pyridazinones obtained from mucochloric and mucobromic acid lead to the corresponding 5-alkylamino-3(2H)-pyridazinones, which were tested as platelet aggregation inhibitors.     

Synthesis of 5-Amino-4-imino-3,4-dihydropyrido[3,4-d]pyridazin-1(2H)-one Derivatives

Russian Journal of Organic Chemistry -