Synthesis of Certain Fused Thienopyrimidines of Biological Interest

4‐(4‐Acetylphenylamino)cycloocteno[4,5]thieno[2,3‐d]pyrimidine ( 4 ) was prepared and condensed with certain aldehydes, phenylhydrazine, malononitrile to obtain 5a‐d , 6 and 7 , respectively. 4‐Hydrazino & 4‐substituted amino derivatives of 2‐arylcycloocteno[4,5]thienopyrimidines 10a‐c & 11a‐i were synthesized. Cyclization of the hydrazino compounds 10a‐c with orthoalkanoate esters or the arylidene derivatives 12a‐c with bromine in acetic acid afforded the fused triazolo system 13a‐i . Reaction of the hydrazino compound 10c with acetic anhydride gave 15 while the reaction of 10b,c with acid chlorides gave 16a‐d . Furthermore, the tetrazolothienopyrimidines 17a‐c were synthesized. Some of the newly synthesized compounds were tested for their antimicrobial activity.     

Synthesis of Pyrimidines,Thienopyrimidines, and Pyrazolopyrimidines

5-Ethoxycarbonyl-4-methyl-2-phenylpyrimidin-6(1H)-thione ( 3 ), which was prepared from the reaction of ethyl g -aminocrotonate 1 with benzoyl isothiocyanate ( 2 ) in refluxing acetone, was reacted with a series of halopgenated reagents to give S-alkyl derivatives 4a-g . Upon treatment of compounds 4a-c with sodium ethoxide were cyclized into thienopyrimidine 10a-c . Pyrimidinethione 3 was reacted with hydrazine hydrate to give hydroxypyrazolopyrimidine derivative 6 . The later compound was obtained by heating compound 4a with hydrazine hydrate under neat conditions, but when the reaction was carried using hydrazine hydrate in ethanol, the corresponding carbohydrazide 5 was produced.     

Synthesis,Reactions, and Pharmacological Activities of Some Pyrimidines Using (<Emphasis Type="Italic">N</Emphasis>-Methylindolyl)acetic Acid as Synthon

Summary. A series of pyrimidinones, thienopyrimidines, and their derivatives were synthesized using N-methylindolyl acetic acid as a starting material. Sixteen new heterocyclics containing a pyrimidine ring were thus prepared. The pharmacological screening showed that many of these compounds have good analgesic and antiparkinsonian activities comparable to Voltarene^? and Benzatropine^? as reference drugs. The structure assignments of the new compounds based on chemical and spectroscopic evidence. The detailed synthesis, spectroscopic data, and pharmacological properties are reported.     

Synthesis,Spectroscopic Studies of Fluorinated Pyrimido‐1,2,4‐Triazines: Protective Effect Against Some Plant Pathogenic Fungi

In search for new biologically active compounds, several new fluorine‐substituted pyrimido [2,3‐c][1,2,4]triazino ( 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ) have been synthesized via the nucleophilic attack of 2‐hydrazinopyrimidinone ( 2 ) toward more positive carbons under different conditions. Structure of the newly synthesized compounds was deduced from elemental analyses as well as their spectral data (UV, IR, NMR, and M/S). The antifungal activity of the target ring systems has been evaluated both in vitro and in vivo against some phytopathogenic fungi associated with wheat grains. Result showed that compounds 6 , 7 , and 8 have high protection of wheat grains against the fungal infection.     

嘧啶类酪氨酸激酶抑制剂

酪氨酸激酶在肿瘤的发生、发展过程中起着非常重要的作用,已成为肿瘤治疗的新靶点.嘧啶类化合物是蛋白酪氨酸酶抑制剂(PTKIs)中的一大类,这类化合物在临床前期研究中显示具有很好的抗肿瘤效应,一些已在临床上作为很有前景的抗癌药.本文按其结构类别介绍了近年来报道的嘧啶类酪氨酸激酶抑制剂.     

Quantitation of Purines and Pyrimidines in Human Serum by High-Performance Liquid Chromatography

Abstract

A high-performance liquid chromatography assay was developed for the purpose of examining xanthine, hypoxanthine, uridine, thymidine, allopurinol, and oxypurinol in serum of patients with advanced carcinoma treated with methorexate and 5-fluorouracil. After the addition of an internal standard, serum samples were extracted of purines and pyrimidines with trichloroacetic acid and neutralized with tert-amine. Aliquots of the extracted serum were injected onto a C18 reverse-phase column and purines and pyrimidines were eluted with a gradient of MeOH/H₂O and KH₂PO₄ solutions. Absorbance was detected with a variable-wavelength UV spectrophotometer at 254 nm and 280 nm. This assay can be readily applied to quantitate baseline and treatment-induced variations in serum purine and pyrimidine levels which may correlate with clinical response and/or toxicity in patients with cancer.     

Design,Synthesis, and Antimicrobial Evaluation of Novel Thienopyrimidines and Triazolothienopyrimidines

2-Cyanoacetohydrazide and 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene derivatives were exploited as starting materials for the syntheses of novel thienopyrimidines and triazolothienopyrimidines. The proclivity of these compounds toward one-carbon donor reagents such as carbon disulfide, phenyl isothiocyanate, and aromatic aldehydes was investigated. The structures of all synthesized compounds were ascertained by spectral and analytical data. The antimicrobial activity of the target synthesized compounds was tested against various microorganisms.     

Synthesis and Reactions of Some New Thienopyrimidines

4-Methyl-6-mercapto-2-phenylpyrimidine-5-carbonitrile ( 1 ) was reacted with different halo compounds, namely ethylchloroacetate, chloroacetone, bromoacetanilide, p-chlorobromoacetanilide, and p -methoxy chloroacetanilide in ethanol in the presence of sodium acetate yielded the corresponding S-alkylated derivatives ( 2a-e ). The latter compounds underwent cyclization into thienopyrimidines ( 4a-e ) upon treatment with sodium ethoxide in ethanol. The reaction of ( 4a ) with hydrazine hydrate led to the formation of 5-amino-4-methyl-2-phenylthieno[2,3-d]pyrimidine-2-carbohydrazide ( 5 ). Compound ( 5 ) was reacted with a variety of reagents to produce other new thienopyrimidines as well as oxadiazolylthienopyrimidines ( 6, 11 ).     

Heterocyclic Synthesis with Nitriles: Synthesis of Pyrazolopyrimidine and Pyrazolopyridine Derivatives

The reaction of N ₁-substituted-5-amino-4-cyanopyrazoles with malononitrile and diethylmalonate occurs with formation of 6-substituted pyrazolo[3,4-d]pyrimidines, and pyrazolo[3,4-b]pyridines respectively. The structures of the products and conceivable mechanisms are discussed.     

Synthesis of Some Novel Imidazopyrazole and Pyrazolopyrimidine Derivatives

5‐Amino‐3‐anilino‐1H‐pyrazole‐4‐carbonitrile 1 was alkylated with various halo reagents under phase transfer conditions to give the corresponding imidazopyrazole derivatives 2a , 2b , 2c , 3 , 4 , 5 , 6 . Pyrazolo[1,5‐a] pyrimidine derivatives 11 , 12 , 13 , 14 were prepared by treating compound 1 with different dicarbonyl reagents, namely, diethymalonate, ethyl 3‐oxo‐3‐phenylpropanoate, pentane‐2,4‐dione or ethyl 3‐oxobutanoate.     

Reactions of Benzoyl Isothiocyanate with Active Methylene Reagents: A Novel Synthesis of Thiophene,Thiazoline and Thieno[2,3-d]Pyrimidine Derivatives

Various derivatives of thiophene, thiazoline and thienopyrimidine have been synthesized via the reaction of active methylene reagents (la-j) with benzoyl isothiocyanate in the presence of potassium hydroxide, followed by the subsequent treatment of the potassium salt intermediates 2a-j with phenacyl bromide or ethyl chloroacetate. The stability of the formed adducts 3 and 12 or their selective cyclization depends on both the nature of the active methylene reagent and the α-halocarbonyl compounds.     

Synthesis of Steroidal Pyrimidines

Selected aryl aldehydes were treated with 17-oxo-5-androsten-3β-yl acetate (I) to give the corresponding 16-arylidene 17-oxo-5-androsten-3β-yl acetates(IIa-e). Condensation of these chalcones with urea revealed the formation of the corresponding substituted pyrimidin-2′-ones (IIIa-e) respectively.     

One‐Pot Synthesis of Pyrimidines via Cyclocondensation of β‐Bromovinyl Aldehydes with Amidine Hydrochlorides

A series of pyrimidines were prepared by cyclocondensation of β‐bromovinyl aldehydes with amidine hydrochlorides in the presence of Et₃N in excellent yields (74–95%).     

Thienopyrimidines: synthesis, properties, and biological activity

Data on the methods for the synthesis of isomeric thienopyrimidine derivatives, their chemical transformations, and biological activities are systematized and analyzed. Emphasis is given to studies published over the last 10—15 years.     

Synthesis of Some New Polyfused Thienothiophenes Part 4: Synthesis of Thienopyrimidine,Thienotriazine, Thienoimidazotriazine,Thienotriazolotriazine, and Thienotetrazolotriazine Derivatives

3,4-Diamino-2,5-dicarboxamidothieno(2,3-b)thiophene 1 was allowed to react with CS 2 , carbonyl compounds, ethyl chloroformate, S,S-acetals, and oxallyl chloride to give thienopyrimidines 2-6 and thieno-1,4-diazepine 7 . Treatment of compound 1 with nitrous acid afforded compound 8 , which converted into the corresponding chloro derivative 9 by using PCl 5 . Compound 9 was reacted with amino reagents to afford the corresponding thienoimidazotriazines 10 and 11 , thienotriazolotriazines 12 and 13 and 4-hydrazinothienotriazine 14 . Treatment of compound 14 with aldehydes, triethyl orthoformate, CS 2 , nitrous acid and ylidenemalononitriles, afforded thienotriazolotriazine 16-18 , thienotetrazolotriazine 19 , and 4-pyrazolyl-thienotriazine 20-22 derivatives respectively.     

Reaction of 4-Aryl-3-thiosemicarbazides with Phenylisothiocyanate: A Facile Synthesis of Thiazole,Pyrazole and Pyrimidine Derivatives

The reaction of 4-aryl-3-thiosemicarbazides 1a-d with phenylisothiocyanate gave the intermediate potasium salts 2a-d . The latter afforded 3a-d, 13a-d and 19 upon the reaction with phenacyl bromide, monochloroacetic acid and ethyl bromocyanoacetate respectively.     

Heterocyclic Synthesis with Enamines: Convenient Syntheses of Polyfunctionally Substituted Pyrazole,Pyridine, Pyrimidine and Pyrazolo[3,4-d]pyrimrdine Derivatives

Facile syntheses of pyrazole, pyridine, pyrimidine and pyrazolo[3,4-d]pyrimidine derivatives have been achieved by the reaction of β-enamino nitrile 2a with hydrazines, phenyl isothiocyanate, thiourea and active methylene reagents. The β-enamino ketone 2e with the same reagents affords 3,5-dimethyl heterocyclic ring systems.     

Synthesis and Antimicrobial Activity of Azolyl Pyrimidines

A new class of azolyl pyrimidines linked by diamino sulfone moiety was prepared and studied their antimicrobial activity. Chloro‐substituted and nitro‐substituted thiazolyl pyrimidines ( 9c and 9e ) showed excellent antibacterial activity against Bacillus subtilis , while imidazolyl pyrimidines ( 10c and 10e ) exhibited promising antifungal activity against Aspergillus niger .