Synthesis and biological effects of 2,3-diphenyl-5-methoxyindole and substituted benzophenone derivatives

Seven 2,3-diphenyl-5-methoxyindole derivatives were synthesized. The effect of structural variation of these molecules on biological activities was examined. None of the tested compounds was found to be toxic up to 5 gm/Kg body weight. Four compounds demonstrated smooth muscle relaxant effects and one showed a persistent hypotensive effect. Only the parent compound, 2,3-diphenyl-5-methoxyindole, showed a significant analgesic effect.     

Synthesis and antimicrobial activity of some indole derivatives

Bromination of 2,3-diphenyl-5-methylindole (I) (using 3 mol) with bromine gave the 4,6-dibromo derivative (II) which upon oxidation gave the corresponding 2-benzamido benzophenone derivative (III). Bromination (using 6 mol) with bromine afforded the tetrabromo derivative (IVa) which reated with amines to form the corresponding 5-substituted aminomethyl derivatives (IVb-d). Further bromination ofII using only 1 mol gave the tribromo derivative (Va) which in turn reacted with amines to formVb-g. The antimicrobial activities of compoundsI, IVa, IVc, Va, Ve, Vf andVg were studied.     

Cyanoacetic acid hydrazide in heterocyclic synthesis: A new route for the synthesis of several annelated pyran derivatives

Cyanoacetic acid hydrazide reacted with some 2-pyrazolin-5-one, isoxazol-5-one and 2-thiazolin-4-one and their ylidene derivatives to yield several new annelated pyran heterocycles. Structures were established on the basis of elementary analyses and spectral data studies in addition to synthesis via other routes.     

Synthesis and anti-HIV activity of 2,3-diaryl-1,3-thiazolidin-4-ones

Several 1,3-thiazolidin-4-ones bearing a 2,6-dihalophenyl group at C-2 and a variously substituted phenyl ring at N-3 have been synthesized and tested as anti-HIV agents. The results of the in vitro tests showed that some of them proved to be effective inhibitors of HIV-1 replication.     

4-Aza-2,3-didehydropodophyllotoxins: new lignan with antitumor activity obtained from one-step synthesis

Podophyllotoxin, a natural lignan, is a good inhibitor of tubulin polymerization with antitumoral properties but it is too toxic for therapeutic use. In order to obtain less toxic drugs, several heterolignans have been prepared. We presented the synthesis and preliminary pharmacological properties of 4-aza-2,3-didehydropodophyllotoxins (dihydropyrrole [3,4-b]quinolin-1-ones), a new azalignan series. A straightforward synthesis was described according to a multicomponent reaction in a one-pot procedure. Starting from an aniline, an aromatic aldehyde, and a cyclic B-diketone, many substituted analogues could be prepared. Our lead, the 4-aza-2,3-didehydropodophyllotoxin, is extremely cytotoxic on various tumor cell lines, active in vivo on murine tumors. Like podophyllotoxin, this drug inhibits microtubule assembly without any effect on depolymerization.     

Synthesis and anti-HIV activity of 2,3-diaryl-1,3-thiazolidin-4-(thi)one derivatives

Several 2,3-diaryl-1,3-thiazolidine-4-thione derivatives and 2,3-diaryl-1,3-thiazolidin-4-ones bearing a methyl group at C-5 position have been synthesized and tested as anti-HIV agents. The results of the in vitro tests showed that some of them proved to be effective inhibitors of HIV-1 replication.     

Synthesis and preliminary anticancer activity of new 1,4-dihydro-3-(3-hydroxy-2-naphthyl)-4-substituted-5H-1,2,4-triazoline-5-thiones

1,4-Dihydro-3-(3-hydroxy-2-naphthyl)-4-substituted-5H-L2,4-triazolinc-5-thiones were synthesized. The structures of original eight compounds were confirmed by elemental analysis, 1H NMR and mass spectral methods. One of the compounds (3a) was tested in vitro for its anticancer activity against 52 human tumor cell lines.     

Synthesis and biological activity of 5-hydroxy-4-quinolones and 5-methoxy-4-quinolones as truncated acridones

A series of 5-hydroxy-4-quinolone (3) and 5-methoxy-4-quinolone (4) derivatives were synthesized as truncated acridone analogues and evaluated for antitumor, antiherpes and antituberculosis activities. Among them 5-hydroxy-8-methoxy-quinolone showed potent antitumor activity (IC₅₀=17.7 μM for HL60) which was greater than that of acronycine. However, these compounds didn't show any significant antiherpes or antituberculosis activity.     

5-氨基-4-氧代戊酸盐酸盐的制备

乙酰丙酸经酯化、溴化得到5-溴或3-溴-4-氧代戊酸甲酯混合物，无需分离，直接与邻苯二甲酰亚胺钾在DMF中反应得N-[（2-氧代-4-甲氧羰基）丁基]邻苯二甲酰亚胺，最后经稀盐酸酸解得到5-氨基-4-氧代戊酸盐酸盐，总收率接近44％。     

Synthesis and molluscicidal activity of some 1,3,4-triaryl-5-chloropyrazole, pyrano[2,3-c]pyrazole, pyrazolylphthalazine and pyrano[2,3-d]thiazole derivatives

2-(5-Chloro-1,3-diphenyl-1H-pyrazol-4-ylmethylene)-malononitrile 1a reacts with the arylidenes of malononitrile 2a-d to afford the triaryl-5-chloropyrazoles 3a-d, respectively. 1a reacts with the active methylene pyrazolinones 5a, b and 12a, b to afford different products 8, 9, 10, 11, and 14a, b--depending on the substitution in the pyrazole ring. Compound 1a reacts also with the pyridazinone derivative 15 to afford the phthalazinone 16, and with the thiazolinones 17a-c to afford the pyrano[2,3-d]thiazoles 20a-c, respectively. It reacts also with the malononitrile dimer 21a and with ethyl cyanoacetate dimer 21b to yield the pyrazolyl pyridines 22a, b, respectively. The synthesized compounds showed a moderate molluscicidal activity towards Biomphalaria alexandrina snails.     

3-(2,3-二氢苯并呋喃-5-基)丙酸的合成

对甲苯酚在无水碳酸钾作用下与2-溴乙醛缩二乙醇缩合后经Friedel-Crafts反应、NBS溴代、与乌洛托品进行Sommelet反应,得苯并呋喃-5-甲醛,与丙二酸缩合后经10%钯炭在常压下催化氢化还原得雷美替胺的关键中间体3-(2,3-二氢苯并呋喃-5-基)丙酸,总收率约49%.     

5-HT4受体拮抗剂哌波色罗的合成

目的合成5-HT4受体拮抗剂哌波色罗。方法以吲哚-3-羧酸甲酯为原料,在NBS、三乙胺作用下,与3-氯-1-丙醇反应,再经环合、胺解、成盐等反应,合成哌波色罗。结果与结论实验总收率为43%,其结构经熔点、氢谱、质谱测试确证。该方法合成工艺简单,易操作,收率高,成本低。     

Efficient synthesis of 2-substituted 2,3-dihydro-4-quinolones as potential intermediates for 2-substituted 1,2,3,4-tetrahydro-4-quinolone antitumor agents

An efficient method for the synthesis of optically active 2-substituted 2,3-dihydro-4-quinolones has been developed. The key features include the introduction of a chiral side chain and the construction of quinolone skeleton by Mitsunobu alkylation and hydroarylation, respectively.     

The Hypolipidemic Activity of a Series of 2,3-Dihydrophthalazine-l,4-dione Derivatives in Rodents

A series of substituted 2,3-dihydrophthalazine-l,4-dione derivatives as well as the corresponding N,N-diaminophthalamides were prepared and were demonstrated to have potent hypolipidemic activity, lowering both serum triglyceride and cholesterol levels significantly at 20 mg/kg/day after 16 days of dosing in CF₁ male mice. The parent compound, 2,3-dihydrophthalazine-l,4-dione, lowered serum cholesterol 51% and serum triglyceride 43%. 2-(2-Carboxyethyl)-2,3-dihydrophthalazine-l,4-dione demonstrated the best hypocholesterolemic activity, with a 66% reduction after 16 days. The 2-(p-chlorophenyl) derivative demonstrated good activity (>40% reduction) in both screens, as did the 6-methyl-2,3-dihydrophthalazine-l,4-dione derivative. Of the amides, 4-methyk N,N-diaminophthalamide demonstrated the best hypolipidemic activity, affording a greater than 40% reduction. 2,3-Dihydrophthalazine-l,4-dione was found to inhibit the enzyme activity of acetyl CoA synthetase, ATP-dependent citrate lyase, sn-glycerol-3-phosphate acyl transferase, phosphatidylate phosphohydrolase, and mitochondrial citrate exchange of liver. In mice after 16 days of dosing, there was a reduction of cholesterol, triglycerides, neutral lipids, and phospholipids in the liver. Cholesterol and neutral lipids were reduced in rat chylomicrons, very low-density lipoproteins, and low-density lipoproteins. The cholesterol content of the high-density lipoprotein fraction was slightly elevated, but reductions in the triglycerides and phospholipids were observed in this lipoprotein fraction. ³H-Cholesterol distribution studies showed a lower concentration in the major organs and plasma, with a higher ³H-cholesterol content in the stomach and large intestine.     

Synthesis and Action on the Central Nervous System of 3-Substituted 2-Phenyl-2,3-dihydro-4H-1,3,2-benzoxazaphosphorin-4-one 2-Oxide and 2-Sulfide Derivatives

The synthesis of 3-substituted 2-phenyl-2,3-dihydro-4H-1,3,2-benzoxazaphosphorin-4-one 2-sulfide derivatives is described. The action of a series 2-oxide ( 1–6 ) and 2-sulfide ( 7–12 ) derivatives on the central nervous system has been evaluated. Compounds 1–4, 6, 7–10 exhibit neuroleptic activity. Derivatives of sulfide series act as antiserotoninergic drugs.     

Synthesis and receptor binding of new thieno[2,3-d]-pyrimidines as selective ligands of 5-HT(3) receptors

With the aim to develop new potent and selective ligands of 5-HT(3)-type serotonin receptors and to acquire more information on their structure-affinity relationships, new thieno[2,3-d]pyrimidine derivatives 32-39 were synthesized and their binding to 5-HT(3) versus 5-HT(4 )receptors was studied. Some of these new compounds exhibit good affinity for cortical 5-HT(3) receptors, but not for 5-HT(4) receptors. Among these derivatives, 6-ethyl-4-(4-methyl-1-piperazinyl)-2-(methylthio)thieno[2,3-d]pyrimidine 32 is the most potent ligand (K(i) = 67 nM); it behaves as a competitive antagonist of the 5-HT(3) receptor function in the guinea pig colon. Its binding interactions with 5-HT(3A )receptors were analysed by using receptor modelling and comparative docking.     

4-氨基-5-氯-2-乙氧基苯甲酸的合成

目的合成4-氨基-5-氯-2-乙氧基苯甲酸。方法以对氨基水杨酸钠为原料,经酸化、甲酯化、乙酰化、乙基化、氯代、水解等六步反应得到枸橼酸莫沙必利的主要中间体4-氨基-5-氯-2-乙基苯甲酸。结果与结论本合成工艺提高了收率,降低了成本,更适合工业化生产,本工艺总收率为62.4%。     

Synthesis of non-nucleosides: 7- and 1,3-substituents of new pyrrolo[2,3-d]pyrimidin-4-ones on antiviral activity

A series of non-nucleosides 9-47 were synthesized. Compounds 1-4 were reacted with formic acid (85%) to afford compounds 5-8. Then, the latter compounds were reacted with alkyl halides a-f (2-bromopropane, 2-bromobutane, benzyl bromide, benzyl chloromethyl ether, chloromethyl ethyl ether, phenacyl bromide) in the presence of NaH in dry DMF to give the desired compounds 9-47, which were evaluated for activity against herpes simplex virus type-II (HSV-II).