Complete 1H and 13C NMR spectral assignment of benzo[d]isothiazole derivatives and of an isoindole isoster

The complete (1)H and (13)C NMR assignments of the novel compound methyl 2-amino-3-(benzo[d]isothiazol-3-yl)propanoate (1), of 3-amino-5-methylbenzo[d]isothiazole (2) and N-(t-butyloxycarbonyl)-2-aminobenzo[d]isothiazol-3(2H)-one (3) and of the desulfurated isostere of 3, N-(t-butyloxycarbonyl)-2-aminoisoindolin-1-one (4), using 1D and 2D NMR techniques, including COSY, INADEQUATE, HSQC, and HMBC experiments are reported.     

Synthesis,Bioactivity and Crystal Structure Analysis of Novel Benzo[d]isothiazol-3（2H）-ones

Two compounds,3-oxo-N-o-tolylbenzo[d]isothiazole-2(3H)-carboxamide (1) and N-(2-methoxyphenyl)-3-oxobenzo[d]isothiazole-2(3H)-carboxamide (2),were synthesized from the initial compound benzo[d]isothiazol-3(2H)-one (BIT) and characterized by 1 H NMR,IR and elemental analysis,respectively.The single crystals of compounds 1 and 2 were obtained and determined by X-ray diffraction analysis.The preliminary results of biological activity experiment show that some of the title compounds exhibited a favorable antimicrobial activity.     

Condensed isoquinolines. 37.* Heterocyclization using 3-(arylamino)- and 3-(hetarylamino)isoquinolin-1(2H)-ones

The reaction of 3-NHR-isoquinolin-1(2H)-ones (R = Ar) with aromatic aldehydes in the presence of Me3SiCl or in acetic acid leads to the formation of derivatives of dibenzo[b,f][1, 8]naphthyridin-5(6H)- one and benzo[f]isoquino[3,4-b][1, 8]naphthyridine-5,9(6H,7H)-dione. The reaction for R = Het in the presence of Me3SiCl gives derivatives of 5H-pyrido[1',2':1,2]pyrimido[4,5-c]isoquinolin-5-one, benzo[f]isoquinoline[3,4-b][1,8]naphthyridine-5,9[6H,7H]-dione, and derivatives of new heterocyclic systems, 5H-pyrazino[1',2':1,2]pyrimido[4,5-c]isoquinolin-5-one, 5H-[1,3]thiazolo[3',2':1,2]pyrimido- [4,5-c]isoquinolin-5-one, 5-H-benzo[f]pyrazolo[3,4-b][1,8]naphthyridin-5-one, and isoquino[3,4-b]- [1,5]naphthyridin-5(6H)-one. The effect of the structure of substituent R and nature of the substituent in the benzaldehydes on the structure of the reaction products was studied.     

Synthesis and Crystal Structure of 1-（4-Fluorophenyl）-2-hexylthiobenzo[4,5]-furo[3,2-d]-1,2,4-triazolo[1,5-a]pyrimidin-5（1H）-one

The crystal structure of the title compound 1-(4-fluorophenyl) -2-hexylthio-benzo [4,5]furo[3,2-d]-1,2,4-triazolo[1,5-a]pyrimidin-5(1H) -one(C23H21FN4O2S,Mr = 436.5) has been prepared and determined by single-crystal X-ray diffraction. The crystal is of monoclinic,space group P21/n with a = 13.9854(3) ,b = 17.2678(4) ,c = 18.1828(5) ,β = 99.364(2) °,V = 4332.58(18) 3,Z = 4,Dc = 1.338,F(000) =1824,μ = 0.185 mm-1,MoKa radiation(λ = 0.71073) ,R = 0.0538 and wR = 0.1162 for 4728 observed reflections with I > 2σ(I) . X-ray diffraction analysis reveals the fused rings of benzo[4,5]furo[3,2-d]-1,2,4-triazolo[1,5-a] pyrimidin-5(1H) -one system are nearly coplanar. The crystal packing is mainly stabilized by weak intermolecular C-H···O hydrogen bond and π-π interactions.     

Synthesis, docking studies and biological evaluation of benzo[b]thiophen-2-yl-3-(4-arylpiperazin-1-yl)-propan-1-one derivatives on 5-HT1A serotonin receptors

A series of novel benzo[b]thiophen-2-yl-3-(4-arylpiperazin-1-yl)-propan-1-one derivatives 6a-f, 7a-f and their corresponding alcohols 8a-f were synthesized and evaluated for their affinity towards 5-HT(1A) receptors. The influence of arylpiperazine moiety and benzo[b]thiophene ring substitutions on binding affinity was studied. The most promising analogue, 1-(benzo[b]thiophen-2-yl)-3-(4-(pyridin-2-yl)piperazin-1-yl)propan-1-one (7e) displayed micromolar affinity (K(i) = 2.30 μM) toward 5-HT(1A) sites. Docking studies shed light on the relevant electrostatic interactions which could explain the observed affinity for this compound.     

Syntheses of 4-(benzo[b]furan-2 or 3-yl)- and 4-(benzo[b]-thiophen-3-yl)piperidines with 5-HT2 antagonist activity

The syntheses of 4-(benzo[b]furan-3-yl)piperidines, 4-(benzo[b]furan-2-yl)piperidines and 4-(benzo[b]thiophen-3-yl)piperidines with 5-HT₂ antagonist activity are described. Reaction of 1-acetyl-4-(2,4-difluorobenzo-yl)piperidine 2 with methyl glycolate gave methyl 6-fluoro-3-(1-acetylpiperidin-4-yl)benzo[b]furan-2-carboxylate 3 , which was converted to 2-[2-[4-(benzo[b]furan-3-yi)piperidin-1-yl]ethyl-5,6,7,8-tetrahydro-1,2,4-triazolo-[4,3-a]pyridin-3(2H)-one hydrochloride 9 . Analogous benzo[b]furans 17a-d and benzo[b]thiophenes 10a,b and 18a were prepared by a similar method. Cyclization of 4-fluoro-2-(4-pyridinylmethoxy)acetophenones 20a,b afforded 4-(benzo[b]furan-2-yl)pyridines 21a,b , which were converted to 2-[2-[4-(benzo[b]furan-2-yl)-piperidin-1-yl]ethyl-5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-a]pyridin-3(2H)-one hydrochlorides 24a,b. Among them, benzo[b]furans 9 and 17a,d and benzo[b]thiophenes 10 and 18a showed potent 5-HT₂ antagonist activity in vitro.     

N-苯基-3-(p-氯苯)全氢螺[苯并[b]异■唑7,1′环己烷]-4酮的合成及晶体结构

合成并测定了N-苯基-3－（p-氯苯）全氢螺[苯并[b]异唑7，1-环已烷]-4-酮（3）的单晶结构，晶体分子式C24H26ClNO2,Mr=395.93，晶体属单科晶系，空间群为P21／c，晶胞参数结构的偏离因子R=0．037，Rw=0．039。分子3存在着两个螺六员环（A和B），A环具有通常的椅式构型，B环是扭船式构型。B环和五员异呼吐环C环并连，C环有些扭曲，结构分析结果表明，分子3具有“顺-顺”构型。     

The Mechanism on Cyclization, Debenzylation and Oxidation of 1-[1-（Benzyloxy）-3-methylnaphthalen-4-yloxy]propan-2-one

Mansonone compounds represent a series of naturally occurring o-quinones mainly isolated from the heartwood of Mansonia Altissima1 and Ulmus Glabra2. Mansonone F contained oxaphenalene skeleton which was a relatively novel structure and rarely existed in …     

Synthesis of a 6-aryloxymethyl-5-hydroxy-2,3,4,5-tetrahydro-[1H]-2-benzazepin-4-one: a muscarinic (M3) antagonist

A synthesis of the racemic 6-aryloxymethyl-5-hydroxy-2,3,4,5-[1H]-2-tetrahydrobenzazepin-4-one , for evaluation as a muscarinic (M(3)) antagonist, is described. 2-[2-tert-Butyldimethylsilyloxymethyl-6-(2,6-dimethoxyphenoxymethyl)phenyl]propan-2-ol was prepared from 2,6-dimethyl-1-bromobenzene and taken through to N-[3-(2,6-dimethoxyphenoxymethyl)-2-(propen-2-yl)phenyl]methyl-N-prop-2-enyl 2-nitrobenzene sulfonamide . However, attempts to cyclise this diene by alkene metathesis were unsuccessful, the open-chain alkene being the only product isolated in yields of up to 70%. In a second approach to the 6-aryloxymethyl-5-hydroxytetrahydrobenzazepin-4-one, methyl (Z)-3-[2-(1-tert-butyldimethylsilyloxymethyl)-6-(1,6-dimethoxyphenoxymethyl)phenyl]but-2-enoate was converted into (Z)-3-[2-hydroxymethyl-6-(2,6-dimethoxyphenoxymethyl)phenyl]but-2-enyl 2-nitrobenzene sulfonamide which was cyclised under Mitsunobu conditions to the corresponding 2,3-dihydro-[1H]-2-benzazepine . The structure of this was confirmed by an X-ray crystal structure of its 2-(4-bromophenylsulfonyl) analogue , and functional group modification including hydroxylation, attachment of the requisite side-chain at C(2) and further oxidation gave the target compound which was assayed for muscarinic (M(3)) activity.     

S-烃基-1-烃基-3-[4-(苯并咪唑-2-巯基)苯基]异硫脲的合成及其iNOS抑制活性

以2-巯基苯并咪唑(1)为原料,经缩合和还原得到2-(4-氨基苯硫基)苯并咪唑(3),再与异硫氰酸苯甲酰酯或异硫氰酸烃基酯反应得到取代硫脲(5和7),最后与卤代烃反应得到20个新的S-烃基-1-烃基-3-[4-(苯并咪唑-2-巯基)苯基]异硫脲化合物(6和8),其结构经IR,¹HNMR,MS及元素分析确证.初步的药理试验表明,20个目标化合物均有不同程度的iNOS抑制活性,其中化合物6b,8d和8f的iNOS抑制活性与阳性对照药氨基胍相当.     

3a, 4-二氢-苯并吡喃[4,3-c]吡唑-3(2H)-酮类衍生物的合成及其活性

设计合成了33种新型的3a, 4-二氢-苯并吡喃[4,3-c]吡唑-3(2H)-酮类化合物,其结构经MS,1H NMR和元素分析的确证。并对化合物7k的单晶进行了结构测定。初步生物活性测试表明标题化合物具有一定的杀虫杀菌活性。     

Some Transformations of 3-(2,2-Dimethyltetrahydro-2H-pyran-4-yl-2-thioxo-2,3-dihydro-1H-spiro(benzo[h]quinazoline-5,1'-cycloheptan)-4(6H)-one

Russian Journal of Organic Chemistry - Starting from 3-(2,2-dimethyltetrahydro-2H-pyran-4-yl)-2-thioxo-2,3-dihydro-1H-spiro(benzo[h]quinazoline-5,1'-cycloheptan)-4(6H)-one, a series of...     

Synthesis,crystal structure,and density functional theory study of a new compound 4-(2-chlorobenzyl)-1-(5-fluoro-2-hydroxy-3-(thiomorpholinomethyl)phenyl [1,2,4]triazolo[4,3-a]quinazolin-5(4H)-one

In this paper, a novel SHP244 derivative 4-(2-chlorobenzyl)-1- (5-fluoro-2-hydroxy-3- [thiomorph-olinomethyl] phenyl)- [1,2,4]triazolo [4,3-a] quinazolin-5(4H)-one was synthesized through five steps. The single crystals were grown in a suitable solvent system (dichloromethane and methanol). Its structure was confirmed by ¹H NMR, ¹³C NMR spectroscopy, ESI-MS, m/z: 534.12[M-H] (MS), FT-IR, and X-ray single crystal diffraction. The crystal structure of the title compound was optimized by density functional theory (DFT) calculation. The crystal structure after X-ray single crystal diffraction was compared with the structure optimized by DFT calculation, and the result shows that the two structures are consistent. In order to explore certain physical and chemical properties, the frontier molecular orbital and molecular electrostatic potential of the title compound were analyzed. In addition, the docking of the title compound to the target protein was studied to understand the docking effect of the compound with the target protein.     

Cyclisation of 4-[2-Cyclofentenyl]-3-Hydroxy [1] Benzopypan-2-One

4-[2-cyclopentenyl]-3-hydroxy [1] bonzopyran-2-one(3) was cyclised to the bicyclie coumar in-1,3-ethano-2-bromo-1,2-dihydro-3H-pyrano [2,3-c] [1] benzopyran-5-one (6) by a sequence of reactions viz. acetylation of 3, addition of bromine to cyclopenteny double bond and treating the resulting acetyldibromo compound (5) with 4% alcoholic KOH, Cyclisation of compound (3) with mercuric acetate in methanol gave condensed furan derivative 7 which on reductive demercuration with zinc borohydride in dimethoxyethane gave the 1,3-propano-1,2-dihydrofuro [2,3-c] [1] benzopyran-4-one, 8. Cyclisation of compound 2 with come. H₂SO₄ furnished a mixture of bicyclic derivative 9 ad furo coumarin derivative 8.     

Synthesis and activity of a metabolite of (S)-6-amino-5-(6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxamido)-3-methyl-1-phenyl-2,4-(1H,3H)-pyrimidinedione (CX-659S)

CX-659S (1) [(S)-6-amino-5-(6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxamido)-3-methyl-1-phenyl-2,4-(1H,3H)-pyrimidinedione], has been developed as a new type anti-inflammatory agent for the treatment of dermatitis. The structure of a major metabolite of CX-659S was determined as (S)-6-amino-5-[2-hydroxy-2-methyl-4-(2,4,5-trimethyl-3,6-dioxo-1,4-cyclohexadienyl)butanamide]-3-methyl-1-phenyl-2,4-(1H,3H)-pyrimidinedione (2) by direct comparison with the synthesized authentic compound. The anti-inflammatory activity of 2 was equipotent with that of 1 on the contact hypersensitivity reaction (CHR) induced by picryl chloride (PC) in mice, suggesting that compound 2 contributes, at least in part, to the anti-inflammatory activity of CX-659S.     

Synthesis, structure and antifungal activity of new 3-[(5-aryl-1,3,4-oxadiazol-2-yl)methyl]benzo[d]thiazol-2(3H)-ones

A series of new 3-[(5-aryl-1,3,4-oxadiazol-2-yl)methy])benzo[d]thiazol-2(3H)-ones were synthesized by reaction of (5-substituted-2-oxobenzothiazolin-3-yl)-acetohydrazide with various aromatic acids in POCl(3) under reflux conditions. The structures of the title compounds were confirmed by 1H-NMR, 13C-NMR, IR, MS and elemental analysis. Furthermore, the structure of compound 4i was determined by single-crystal X-ray diffraction. The preliminary bioassy results indicated that some of them showed moderate inhibition activity against Colletotrichum orbiculare, Botrytis cinerea and Rhizoctonia solani.     

Synthesis,crystal structure,DFT, molecular docking and antitumor activity of 4-(2-chlorobenzyl)-1-(5-fluoro-2-hydroxy-3-((4-methylpiperidin-1-yl)methyl)phenyl)-[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-one

Research on Chemical Intermediates - In this study, the compound 4-(2-chlorobenzyl)-1-(5-fluoro-2-hydroxy-3-((4-methylpiperidin -1-yl)methyl)phenyl)-[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-one (1)...     

Synthesis of (s)-1-{3-[4-(4-benzo[d]isothiazol-3-yl-piperazin-1-yl)-3-fluoro-phenyl]-2-oxo-oxazolidin-5-ylmetyl}-3-substituted-urea derivatives as antibacterial agents

A new series of (s)-1-{3-[4-(4-benzo[d]isothiazol-3-yl-piperazin-1-yl)-3-fluoro-phenyl]-2-oxo-oxazolidin-5-ylmetyl}-3-substituted-urea derivatives have been synthesized and characterized with spectral data, such as IR, NMR and Mass spectroscopies. All compounds are in vitro evaluated for their efficacy as antimicrobial agent against the gram-positive pathogenic strains such as Bacillus subtilis ATCC 6633, Staphylococcus aureus ATCC 25923, Staphylococcus epidermidis ATCC 12228 and Streptococcus pyogens ATCC 8668. Five compounds ( 19k , 19l , 19m , 19n and 19o ) out of 15 compounds showed moderate activity.     

Synthesis of 1-[6-Fluoro-(2S)-3H,4H-dihydro-2H-2-chromenyl]-(1R)-1,2- ethanediol and 1-[6-Fluoro-(2R)-3H,4H-dihydro-2H-2-chromenyl]- (1R)-1,2-ethanediol

Benzopyran compounds possess diverse pharmacological properties such as β-blockade, anticonvulsant and antimicrobial.[1,2] Our interest has been focused on the synthesis of 1-[6-Fluoro-2S]-3H,4H-dihydro-2H-2-chromenyl]-(1R)-1,2-ethanediol (6) and 1-[6-fluoro-(2R)-3H,4H-dihydro-2H-2-chromenyl]-(1R)-1,2-ethanediol (7) which are particularly convenient precursor to (S,R,R,R)-NE (8). 8 containing four asymmetrical carbon atoms was reported to be the most active isomer.[3] Chandrasekhar[4] has reported on the synthesis of 8. The key step to synthesize this compound is to obtain the chiral chromanone 6 and 7. 6 was accomplished in 8 steps by the Clasien rearrangement and a one-pot Sharpless asymmetric epoxidation, but the compound 7 was accomplished in 10 steps. Johannes[5] used Zr-catalytic kinetic resolution of allylic ethers and Mo-catalyzed chromene formation to synthesize 8 in 14 steps. However both of the methods request many synthetic steps and expensive reagents.     

微波法合成2-羟乙基苯并[d]异噻唑-3(2H)-酮

以苯并异噻唑-3(2H)-酮(BIT)及氯乙醇为原料微波法合成了2-羟乙基苯并[d]异噻唑-3(2H)酮。考察了氢氧化钠量,氯乙醇用量,反应时间,反应温度对反应的影响,经正交实验设计得到了最佳反应条件,最佳反应条件下收率为83.3%。结果表明,与传统工艺相比,微波技术合成2-羟乙基苯并[d]异噻唑-3(2H)-酮的方法具有操作方便、收率高等特点,具有一定的应用价值。