Complexes with biologically active ligands. Part 4. Coordination compounds of chlorothiazide with transition metal ions behave as strong carbonic anhydrase inhibitors

Complexes of the diuretic benzothiadiazine derivative chlorothiazide (6-chloro-7-sulfamoyl- 1,2,4-benzothiadiazine-1,1-dioxide) with V(IV); Fe(II); Co(II); Ni(II); Cu(II), Ag(I) and U(VI) were prepared and characterized by elemental analysis, spectroscopic, thermogravimetric, magnetic and conductimetric measurements. The complexes behave as effective inhibitors for two isozymes (I and II) of carbonic anhydrase (CA).     

Complexes with biologically active ligands. Part 11. Synthesis and carbonic anhydrase inhibitory activity of metal complexes of 4,5-disubstituted-3-mercapto-1,2,4-triazole derivatives

Complexes containing five 4,5-disubstituted-3-mercapto-1,2,4-triazoles and Zn(II), Hg(II) and Cu(I) were synthesized and characterized by standard procedures (elemental analysis; IR, electronic and NMR spectroscopy, conductimetry and TG analysis). Both the thione as well as the thiolate forms of the ligands were evidenced to interact with the metal ions in the prepared complexes. The original mercaptans and their metal complexes behave as inhibitors of three carbonic anhydrase (CA) isozymes, CA I, II and IV, but did not lower intraocular pressure in rabbits in animal models of glaucoma.     

1,3,4-thiadiazole derivatives. Part 9. Synthesis and biological activity of metal complexes of 5-(2-aminoethyl)-2-amino-1,3,4-thiadiazole

Metal complexes of the title ligand (L) containing Co(II), Ni(II) and Cu(II) were prepared and characterized by elemental analysis, IR, electronic spectroscopy and conductimetry. The new derivatives, possessing the following formulae, CuL(2)(OH)(2), NiL(2)Cl(2), and [Co(2)LCl(4)](n) showed in vitro antifungal activity against Aspergillus and Candida spp.     

5-[2-(N-(Substituted phenyl)acetamide)]amino-1,3,4-thiadiazole-2-sulfonamides as Selective Carbonic Anhydrase II Inhibitors with Neuroprotective Effects

In this study, 22 novel compounds were designed and synthesized by acetamide bridge chains, among which 5 a – 5 k were monosubstituted compounds, and 6 a – 6 k were disubstituted. A series of biological evaluations was then carried out to determine the carbonic anhydrase inhibitory activity, neuroprotective effects and cytotoxicity of 5 a – 5 k and 6 a – 6 k . The results showed that some compounds could protect PC12 cells from sodium nitroprusside (SNP)-induced damage. In terms of the neuroprotection and inhibitory activity against carbonic anhydrase II, monosubstituted compounds were better than disubstituted. Compound 5 c exhibited better protective effect in PC12 cells than that of edaravone, and 5 c also showed less cytotoxicity. In addition, compound 5 c was found to be the most effective selective carbonic anhydrase II inhibitor (IC₅₀=16.7 nM, CAI/CAII=54.3), which was similar to the inhibitory effect of acetazolamide. Moreover, the selectivity of compound 5 c was better than that of acetazolamide (IC₅₀=12.0 nM, CAI/CAII=20.8). Molecular docking presented that the binding effect of compound 5 c with carbonic anhydrase II was superior to that of 5 c with carbonic anhydrase I and IX, which was consistent with the inhibitory results. Based on above findings, compound 5 c may be a potential candidate for selective carbonic anhydrase II inhibitor, and it had obviously neuroprotective effect and great advantages in drug safety.     

Complexes with biologically active ligands. Part 1. Synthesis of coordination compounds of diazoxide with transition- and main-group cations

Complexes of diazoxide (3-methyl-7-chloro-1,2,4-benzothiadiazine-1,1-dioxide) - an antihypertensive and hyperglycemic pharmacological agent - with a series of transition- and main-group di-, triand tetravalent metal ions were prepared and characterized by elemental analysis, spectroscopic, thermogravimetric, magnetic and conductimetric measurements. The complexes were tested as inhibitors of the enzyme carbonic anhydrase (CA), proving modest activity towards CA II and better inhibition of CA I.     

3-乙酰基-2-芳基-5-(2-碘苯基)-1,3,4-噁二唑啉化合物的合成与表征

2-碘苯甲酰肼与八种芳醛反应得到相应的酰腙(1 a~1h),后与乙酸酐脱水环化合成3-乙酰基-2-芳基-5-(2-碘苯基)-1,3,4-噁二唑啉化合物(2 a~2h),通过元素分析、IR、1H NMR和MS对化合物2 a~2h的结构进行了表征。     

2-(2-氨基-5-溴-3-吡啶基)-5-(4-吡啶基)-1,3,4-噁二唑的合成

采用微波法,以2-氨基烟酸为起始原料经过溴代,再与异烟肼形成双酰肼,最后环合,合成目标化合物2-(2-氨基-5-溴-3-吡啶基)-5-(4-吡啶基)-1,3,4-噁二唑,收率为80.1%。对脱水闭环的反应时间与收率进行了研究。结果显示,微波加热不仅使反应速度提高了20倍,产物收率也提高了近2倍,而反应时间仅用了30 min。目标化合物经MS和1H NMR确证。     

3-乙酰基-2-芳基-5-（2-碘苯基）-1，3，4-嗯二唑啉化合物的合成与表征

2-碘苯甲酰肼与八种芳醛反应得到相应的酰腙(1 a~1h),后与乙酸酐脱水环化合成3-乙酰基-2-芳基-5-(2-碘苯基)-1,3,4-噁二唑啉化合物(2 a~2h),通过元素分析、IR、1H NMR和MS对化合物2 a~2h的结构进行了表征。     

Ethylene oligomerization promoted by group 8 metal complexes containing 2-(2-pyridyl)quinoxaline ligands

Ni^II, Co^II and Fe^II complexes of 2-(2-pyridyl)quinoxaline were synthesized and used in the ethylene oligomerization with methyl-aluminoxane (MAO) as cocatalyst. The nickel complex system mainly produced α-olefins with good activity, while the cobalt and iron complexes showed only marginal activity.     

Electrochemistry of transition metal complex catalysts. Part 9. One- and two-electron oxidation of iridium complexes with cyclohexane-derived tripod phosphine ligands

The redox chemistry of Ir tripod-type tri-phosphine complexes in dichloromethane is investigated by cyclic voltammetry, hold-ramp experiments, and preparative electrolysis at Pt electrodes. Products are identified by spectroscopic data, as well as EDX and EXAFS results. Complexes with the Ir central atom in the oxidation states +I, +II and +III are detected and several follow-up reactions are possible from those. Most of the intermediates and products are characterized. In particular, experiments in the presence of CO contribute to the assignment of peaks in the cyclic voltammograms. The experimental results for the individual steps are summarized in a comprehensive redox reaction mechanism (mesh scheme) for which most steps are characterized by redox potentials.     

2-(4-氨基苯基)-5-(2-烷氧基苯基)-1,3,4-(噁)二唑的合成及表征

以对硝基苯甲酸和水杨酸甲酯为起始原料合成了两种新的1,3,4-噁二唑类化合物——2-(4-氨基苯基)-5-(2-乙氧基苯基)-1,3,4-噁二唑和2-(4-氨基苯基)-5-(2-戊氧基苯基)-1,3,4-噁二唑。合成过程中,1,3,4-噁二唑化合物上的硝基采用钯碳催化氢化的方法还原成氨基,使后处理变得容易,产率显著提高,分别达98.4%和96%。通过IR和1HNMR确证了相关化合物的结构。     

Synthesis of biologically active 4-benzyl-1(2H)-phthalazinones and 2-aryl-3(2H)-1-benzal-isoindolinones

4-Benzyl-2-1(2H) phthalazonyl derivatives of type 2, 3, 5a, b were synthesized by Mannich reaction of 4-benzylphthalazinone 1 which by the reaction with diazomethane yielded O-methylated derivative 4 . Various 1-benzal-2-substituted aryl-3(2H) isoindolinones 7a–f, 8a–e were also prepared. Its i.r., ¹H-n.m.r. and mass spectra were discussed. Some of them exhibit pronounced antimicrobial activities. A number of phthalazinones have found application in clinical medicine [1–3] due to the their pronounced antipyretic, analgesic and tuberculostatic activity and the importance of some benzylidenephthalimidines as stabilisers for halogen containing high polymers [4] and the local anesthetic activity superior to that of procaine [5], tempted us to procure some new phthalazinones and isoindolinones with biological interest.     

3-N-乙酰基-2-芳基-5-(4-碘苯基)-1,3,4-(噁)唑啉类化合物的合成

4-碘苯甲酰肼（2）与芳醛反应得到相应的酰腙（3a-h），而后与乙酸酐脱水环化成了2-芳基-3-N-丙酰基-5-（4-碘苯基）-1，3，4-噁唑啉类化合物（4a-h），通过元素分析，IR，^1H NMR和MS对化合物4a-h的结构进行了表征。     

Transition metal complexes in organic synthesis. Part 46. Synthesis of 5-arylmethyl-substituted tricarbonyl(1-4-η-cyclohexa-1,3-diene)iron complexes

The reaction of tricarbonyl(η⁵-cyclohexadienylium) iron tetrafluoroborate 3 with the methyl arylacetate 6 , the dimethyl arylmalonate 12 , and the di-tert-butyl arylmalonate 14 provides regio- and stereoselectively the tricarbonyliron-complexed 5-arylmethylcyclohexa-1,3-dienes 7, 13 and 15 .     

(4-咔唑-9-基-苯亚甲基)-(5-咔唑-9-亚甲基-[1,3,4]噻二唑-2-基)-胺的合成与表征

以咔唑、氯乙酸和硫代氨基脲为原料,经亲核取代、闭环反应合成了5-咔唑-9-亚甲基-2-氨基-1,3,4-噻二唑。同时,以咔唑和对氯苯甲醛为原料,在碱性催化剂条件下,在DMF溶液中回流反应得到4-咔唑-9基苯甲醛。两者通过固相研磨的合成方法得到新化合物(4-咔唑-9-基-苯亚甲基)-(5-咔唑-9-亚甲基-[1,3,4]噻二唑-2-基)-胺。通过单因素法对(4-咔唑-9-基-苯亚甲基)-(5-咔唑-9-亚甲基-[1,3,4]噻二唑-2-基)-胺的合成条件进行探讨,确定了合成该化合物的最佳反应条件:反应物物质的量比为1∶1∶1.2,反应时间为20min。其结构经IR、1HNMR、UV-vis和元素分析进行表征。     

1-(5-乙基-1,3,4-噻二唑基)-3-苯基硫脲的合成及生物活性

研究了 1 - ( 5 -乙基 - 1 ,3,4-噻二唑基 ) - 3-苯基硫脲的合成及抗菌活性。以 5 -乙基 - 2 -氨基 - 1 ,3,4-噻二唑和异硫氰酸苯酯为原料 ,在十六烷基三甲基溴化铵催化下 ,合成 1 - ( 5 -乙基 - 1 ,3,4-噻二唑基 ) - 3-苯基硫脲 ,找到了较好的合成工艺条件 ,结果表明 :5 -乙基 - 2 -氨基 - 1 ,3,4-噻二唑和异硫氰酸苯酯的摩尔比为 1∶ 1 .8,乙腈为溶剂 ,水浴加热回流 4.0 h,十六烷基三甲基溴化铵为 2 g,1 - ( 5 -乙基 - 1 ,3,4-噻二唑基 ) - 3-苯基硫脲的产率为 5 9.76%。同时发现 1 - ( 5 -乙基 - 1 ,3,4-噻二唑基 ) - 3-苯基硫脲有较强的抗菌活性     

Synthesis and reactions of 2-(p-chloroanilino)-5- (D-galacto-1,2,3,4,5-pentahydroxypentyl)-1,3,4-thiadiazole

Oxidative cyclization of D -galactose (p-chlorophenyl)thiosemicarbazone gave 2-(p-chloroanilino)-5-( D -galacto-1,2,3,4,5-pentahydroxypentyl)-1,3,4-thiadiazole ( 1 ), whose acetylation afforded 2-[N-acetyl-N-(p-chlorophenyl)]-amino-5-( D -galacto-1,2,3,4,5-pentacetoxypentyl)- 1,3,4-thiadiazole ( 3 ). Its periodate oxidation of the glycol groups gave 2-(p-chloroanilino)-1,3,4-thiadiazole-5-carboxaldehyde ( 4 ), which can be transformed into 1,2-[2-(p-chloroanilino)-1,3,4-thiadiazol-5-yl]-1-hydroxy-2-oxoethane. A number of hydrazones of the formyl thiadiazole was prepared and its reduction with sodium borohydride gave 2-(p-chloroanilino)-5-hydroxymethyl-1,3,4-thiadiazole ( 6 ), whose acetylation gave a mono-O-acetyl derivative ( 7 ). Oxidation of the formyl thiadiazole gave 2-(p-chloroanilino)-1,3,4-thiadiazole ( 9 ). The spectral data of the compounds were discussed.     

4-取代的2-(2-氟-3-三氟甲基苯基)-1,3,4-噁二嗪-5-酮衍生物的合成及其生物活性

以2-氟-3-三氟甲基苯甲酰肼为起始原料,经与氯乙酰氯酰肼化,然后在碳酸钾的作用下进行环合,得到2-(2-氟-3-三氟甲基苯基)-1,3,4-噁二嗪-5-酮,最后通过与各种卤代烃反应,在4位N上引入不同基团,合成了18个未见报道的2-(2-氟-3-三氟甲基苯基)-1,3,4-噁二嗪-5-酮衍生物.所有化合物通过核磁共振鉴定,生物测试结果表明化合物1～化合物3对瓜类炭疽病具有较好的活性.     

1-苯基-3-（4-硝基苯基）-5-（9-蒽基）-2-吡唑啉分子内高位共轭

通过对1-苯基-3-(4-硝基苯基)-5-(9-蒽基)-2-吡唑啉及其相关化舍物的吸收光谱进行比较研究，发现该分子的吸收不同于分子内“Ar—N—N=C-Ar”发色团与蒽发色团的叠加．其中“Ar-N-N=C-Ar”发色团的吸收系数增强了12倍，存在极大的增色效应，蒽的精细吸收峰也均红移了20nm左右．说明两者存在基态下的相互作用．优势构象理论分析表明这是由于基态π电子轨道重叠的高位共轭效应引起的．该发现将有助于解释该类分子激发态下发色团间的非共轭电荷转移以及能量转移，并为寻找更大吸收系数的该类化合物提供了较好的方法．