Synthesis, Bioactivity and Crystal Structure Analysis of 2-(Benzo[d]isothiazol-3-yloxy)-N-(3-cyano-1-(4-fluorophenyl)-1H-pyrazol-5-yl) Acetamide

A novel benzisothiazolin-3-one derivative, 2-（benzo[d]isothiazol-3-yloxy）-N-（3- cyano-l-（4-fluorophenyl）-lH-pyrazol-5-yl） acetamide （8）, was synthesized from the initial compound benzo[d]isothiazol-3（2H）-one （BIT） 1 and 4-fluoroaniline 3. The structure of the target compound 8 was determined by elemental analyses, IR and 1H NMR. The single crystals of intermediate compound 6 and the target compound 8 were obtained and determined by X-ray diffraction analysis. The preliminary biological activity was also evaluated and the results showed tile target compound exhibited a good anti-microbial activity.

Synthesis and bioactivity of a novel series of 3,6-disubstituted 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles

A novel series of 3,6-disubstituted 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles were synthesized by the condensation of 4-amino-5- [2-(4-chlorophenoxymethylbenzimidazole)-1-methylene]-3-mercapto-1,2,4-triazole with various(un)substituted aromatic acids in the presence of phosphorous oxychloride.These compounds were investigated for their inhibitory activity to E.coli methionine aminopeptidase(EcMetAP1).Some of the tested compounds showed significant inhibitory activity.

Synthesis,Crystal Structure and Bioactivity of N-Phenethyl-4-hydroxy-4-phenyl Piperidine Hydrochloride

A novel compound N-phenethyl-4-hydroxy-4-phenyl piperidine hydrochloride （C19H24ClNO·H2O） has been synthesized and structurally characterized by elemental analysis, IR, ^1H NMR spectra and single-crystal X-ray diffraction. The crystal belongs to orthorhombic, space group P212121 with a = 8.6306（8）, b = 11.0464（10）, c = 19.3221（18）A^°, V = 1842.1（3）A^°^3, Z = 4, Dc =1.211 g/cm^3,μ = 0.217 mm^-1, Mr= 335.86, F（000） = 720, S = 0.973, R = 0.0420 and wR = 0.1009 for 3627 unique reflections with 3157 observed ones （I 〉 2σ（I））. In the crystal, the dihedral angles made by piperidine ring with two benzene rings are 84.8（6） and 62.5（7）°, respectively. Intermolecular O-H…O and O-H…Cl hydrogen bonds involving water molecules form chains along the b axis, which stabilizes the crystal structure. The preliminary bioactivity tests indicated that the title compound has good effect of cellular growth inhibition to K562 cells and potential bioactivity of anti-leukemia.

Synthesis, Crystal Structure and Bioactivity of N-(phenethylcarbamothioyl)cyclopent-1-enecarboxamide

The compound N-（phenethylcarbamothioyl）cyclopent-1-enecarboxamide was synthesized by the reaction of cyclopent-1-enecarbonyl isothiocyanate with phenethylamine in acetone, and its structure was characterized by IR, 1H NMR and X-ray crystal structure determination. The crystal of the title compound belongs to triclinic, space group P1 with a = 6.9500（7）, b = 9.4618（9）, c = 11.3256（11）, α = 71.522（9）, β = 81.830（8）, γ = 89.237（8）o, Z = 2, V = 698.80（12）3, Dc = 1.304 g/cm3, μ = 0.225 mm-1, F（000） = 292, R = 0.0413 and wR = 0.1073 for 1996 observed reflections with I 〉 2σ（I）. Intramolecular N（2）–H（2）···O（1） interactions as well as intermolecular N（2）–H（2）···O（1）, N（1）–H（1）···S（1） and C（12）–H（12）···S（1） hydrogen bonds help to stabilize the crystal structure. X-ray diffraction analysis reveals that the structure of the new compound exhibits a one-dimensional infinite chain-like structure. The cytotoxicity of the compound was investigated by MTT assay. The results show that the compound is toxic to A549 tumor cell.

Synthesis, Crystal Structure and Bioactivity of Ethyl 1-((2-Bromophenyl)carbamoyl)-2-(3,4,5-trimethoxyphenyl) cyclopropanecarboxylate

Many small-molecule compounds were reported as microtubule-inhibitor with potential anticancer activities, such as combretastatin-A4（CA-4） analogue. The title compound which is one novel cyclopropylamide analogue of CA-4, namely as ethyl 1-（（2-bromophenyl）carbamoyl）-2-（3,4,5-trimethoxyphenyl）cyclopropanecarboxylate, has been synthesized and its crystal structure was characterized by X-ray single-crystal diffraction. The crystal belongs to monoclinic, space group P21/n with a = 8.8002（6）, b = 11.4525（8）, c = 21.7870（16） ?, b = 93.810（3）o, V = 2190.9（3） ?3, Z = 4, C22H23BrNO6, Mr = 477.32, Dc = 1.447 Mg/cm3, F（000） = 980, λ（Cu Kα） = 1.54178 ?, μ = 2.883 mm–1, R = 0.0691 and wR = 0.1958 for 6420 observed reflections（I > 2σ（I））. Importantly, the compound revealed potential anticancer activities in six cancer cells and could stimulate tubulin polymerization in vitro, indicating that the small-molecule could be selected as a lead compound for the development of microtubule stimulator.

Synthesis of Atrazine-HPCD Inclusion and Its Bioactivity

The inclusion of atrazine with 2-hydroxypropyl-β-cyclodextrin(HPCD) was synthesized by ultrasonic method, and it was characterized by UV, XRD and 1H NMR. The solubility in water and the bioactivity of the inclusion were also studied here. The results indicated that the UV maximum absorption wavelength of the inclusion remained at 223 nm, while its intensity decreased. The XRD peaks of atrazine disappeared, weakened and shifted in the inclusion, and the chemical shift of H-3 and H-5 of cyclodextrin inner cavity led to the upfield. The characterization data showed that the atrazine-HPCD inclusion had already formed. At the same time, the solubility of the atrazineHPCD inclusion in water became 20.08 times as that of atrazine. Moreover, the atrazine-HPCD inclusion had better herbicidal activity. When the concentration of the inclusion was 6.5 mg/mL, the inhibition ratios of the inclusion to taproot length, taproot fresh weight, sprout length and sprout fresh weight of barnyard grass were 66.96%, 57.22%, 70% and 57.53%, respectively, which were all higher than those of atrazine.

Mulberry Diels-Alder-type adducts:isolation,structure,bioactivity,and synthesis

Mulberry Diels-Alder-type adducts(MDAAs)are unique phenolic natural products biosynthetically derived from the intermolecular[4+2]-cycloaddition of dienophiles(mainly chalcones)and dehydroprenylphenol dienes,which are exclusively distributed in moraceous plants.A total of 166 MDAAs with diverse skeletons have been isolated and identified since 1980.Structurally,the classic MDAAs characterized by the chalcone-skeleton dienophiles can be divided into eight groups(Types A−H),while others with non-chalcone dienophiles or some variations of classic MDAAs are non-classic MDAAs(Type I).These compounds have attracted significant attention of natural products and synthetic chemists due to their complex architectures,remarkable biological activities,and synthetic challenges.The present review provides a comprehensive summary of the structural properties,bioactivities,and syntheses of MDAAs.Cited references were collected between 1980 and 2021 from the SciFinder,Web of Science,and China National Knowledge Internet(CNKI).

Synthesis and activity of hydroxyethylene peptidomimetic inhibitors of humanβ-secretase

A series of β-secretase peptidomimetic inhibitors with Leu＊Ala hydroxyethylene dipeptide isostere were synthesized and their β-secretase inhibitory activities were measured. The most potent compound N9 showed an inhibitory rate of 59.66% （10 mg/mL）. Compound N9 might be further modified by means of computational chemical methodology.

The synthesis, bioactivity and paramagnetic resonance of angiotensin Ⅱ and its spin labelled derivative

ANGIOTENSIN Ⅱ(Ang Ⅱ) is an important constituent in renin-angiotension system (RAS).The amino acid sequence of Ang Ⅱ is DRVYIHPF. Ang Ⅱ plays an important role both inmaintenance of normal blood pressure and in occurrence of hypertension. Ang Ⅱ binding re-ceptor can induce many kinds of physiological effects. Spin labeling is an effective method thatgreatly deepened the knowledge in structure, movement and interaction of biologicalmolecules. For example, it has been used in studying interaction of antigen and antibody suc-

Synthesis of Novel Antifungal Triazole Compounds

Based on our previous studies of 3D-QSAR, 38 novel objective compounds belonging to 4 series were designed and successfully synthesized directed by the idea of reconstructing the structure of non-pharmacophores while reserving essential ones in triazoles. In vitro pilot studies on their antifungal activities showed that most compounds have inhibitory effects on C.albicans and some inhibit S.cerevisiae also. The effects on C.albicans of 5 compounds are more potent than or equal to that of fluconazole or itraconazole.

Synthesis and Crystal Structure of Spiro[1-bromo-4-methoxy-5-oxa-6-oxo-bicyclo[3.1.0]hexane-2,2′-(3′-cyclohexanoxy-4′-methoxybutyrolactone]

The crystal of the title compound 6 has been prepared and determined by X-ray diffraction analysis. It belongs to the orthorhombic system, space group P212121 with a = 10.195(2), b = 11.955(2), c = 14.335(3) ?, C16H21BrO7, Mr = 405.24, V = 1747.0(6) ?3, Z = 4, Dc = 1.541 g/cm3, μ = 2.387 mm-1, F(000) = 832, R = 0.0266 and wR = 0.0348 for 2110 observed reflections with I > 2σ(I). The crystal exhibits a characteristic spiral structure consisting of one cyclopropane and two butyrolactones with envelope configuration. The intermolecular hydrogen bond between C(16)– H(16)…O(1) and C(3)–H(3)…O(2) has been observed in the crystal lattice.

Ultrasound-assisted synthesis and preliminary bioactivity of novel 2H-1,2,4-thiadiazolo[2,3-a]pyrimidine derivatives containing fluorine

Eight novel 5,7-disubstituted-2-{5-methyl-3-（4-trifluoromethylphenyl）isoxazol-4-ylcarbonylimino}-2H-1,2,4-thiadiazolo[2,3- a]pyrimidines were synthesized by multi-step reactions in yields 68-85%.Reactions were carried out either by ultrasound irradiation or conventional method,and found it was faster and more efficient under ultrasonic irradiation.Preliminary herbicidal activities against Echinochloa crus-galli,Digitaria sanguinalis and Chenopodium serotinum were also evaluated by flat-utensil method,and the results indicated that the target compounds exhibited significant activities,some were even higher than the control herbicide.

Syntheses and Bioactivity of 4″-Sulfonate-5-triphenylsilyl Avermectin B_(1a) and Ivermectin B_(1a) Derivatives

Fourteen new derivatives of avermectin B_(1a) and ivermectin B_(1a) were synthesized from C_5-O-triphenylsilyl avermectin B_(1a) and ivermectin B_(1a)(yield from 40% to 83%). Their chemical structures were characterized by means of IR, ()~1H NMR, ()^(13)C NMR and FAB-MS spectrometries. Some of them show excellent insecticidal activity.

Synthesis, Crystal Structure and Herbicide Activity of Three Phenyl-naphthyl Methanone Derivatives

Three phenyl-naphthyl methanone derivatives have been designed and synthesized through alkylation and Friedel-Crafts acylation reactions.All the compounds were characterized by IR,1H NMR,13C NMR and H RMS.The single crystal structure of the compounds has been further determined by X-ray diffraction.(4-Ethoxynaphthalen-1-yl)(2-methylphenyl)methanone(3a)crystallizes in monoclinic system,P21/c space group with a=13.144(3),b=11.041(2),c=11.320(2)?,β=106.65(3)°,V=1573.7(5)?3,Dc=1.225 Mg/m3,Z=4,F(000)=616,μ(MoKα)=0.078 mm-1,R=0.0928 and wR=0.1556.(4-Ethoxynaphthalen-1-yl)(2-hydroxyphenyl)methanone(3b)belongs to the monoclinic system,P21/c space group with a=9.985(2),b=10.814(2),c=14.353(3)?,β=105.49(3)°,V=1493.6(5)?3,Dc=1.300 Mg/m3,Z=4,F(000)=616,μ(MoKα)=0.087 mm-1,R=0.0568 and wR=0.1262.(4-Methoxynaphthalen-1-yl)(4-methylphenyl)methanone(3c)crystallizes in monoclinic system,P21/c space group with a=7.6130(15),b=15.068(3),c=12.880(3)?,β=100.63(3)°,V=1452.1(5)?3,Dc=1.264 Mg/m3,Z=4,F(000)=584,μ(MoKα)=0.081 mm-1,R=0.0804 and wR=0.1349.The presence of van der Waals forces leads to the stability of the compounds.Especially,compounds 3a^c showed herbicidal activity against the monocotyledon plant barnyard grass(Echinochloa crus-galli).At the concentration of 0.75 mmol/m^2,compound 3b(Ct=0.436±0.116 mg/g)exhibited better activity than pyrazoxyfen(Ct=0.537±0.073 mg/g).

Synthesis of 5-Substituted Hexahydro-1H-1, 4-Diazepine Analogues

5-Substituted hexahydro-1H-1,4-diazepine analogues were synthesized starting from N,N'-dibenzyl-1, 2-ethylenediamine and methyl 2, 4-dibromide butyrate through nucleophilic substitution, reduction, chlorination, debenzylation and amidation. Bioactivity tests showed that 9a had the highest agonist activity.

A brief overview of classical natural product drug synthesis and bioactivity

Traditional medicines consisting of compounds derived from natural organisms have been used for human health care worldwide since ancient times.Since the last century,huge numbers of bioactive natural entities with diverse chemical scaffolds have been discovered,and some have been explored as clinical medications to treat various diseases.The advent of modern technologies has promoted the discovery of natural product-based pharmaceutical agents.The synthesis of natural products not only paves the way to confirm their molecular structures but also offers the structural modification opportunity to rationally optimize the drug-likeness parameters and evaluate the bioactivity of analogs.By providing a brief overview of a miscellaneous collection of complex natural products synthesis and the efforts of the structure–activity relationship,the present report aims to highlight the impact of chemical synthesis in natural product generation,diversification,bioactivity evaluation,and natural product-based drug development.

Exploration of a Library of Triazolothiadiazines as Potent Plant Growth Promoters: Design, Synthesis, X-ray Diffraction Analysis and Bioactivity Studies

A series of novel 3-methyl-6-aryl-7-aroyl-6,7-dihydro-5H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines were designed,synthesized and tested for their antiproliferative activity against HepG2 cell lines in vitro by the standard SRB assay and plant growth regulation activities on wheat(amonocotyledon)and radish(adicotyledon).The results indicated all the title compounds exhibited a very weak antiproliferative activity against HepG2 cell lines in vitro unexpectedly,while showed potent plant growth-regulating activities on both wheat and radish.The crystal structure of trans-4 d was obtained from X-ray diffraction:C18H13N4OSCl3,Mr=439.75,monoclinic system,space group P21/n,a=5.3224(7),b=14.3578(18),c=24.442(3)A,β=94.180(2)°,V=1862.8(4)A3,F(000)=899,Z=4,Dc=1.5679 g/cm^(3),λ=0.71073A,μ=0.621 mm-1 and the final R=0.0382 for 3274 unique reflections with 2851 observed ones(I>2σ(I)).

Synthesis, X-ray Crystallographic Analysis and Bioactivities of α-Aminophosphonates Featuring Pyrazole and Fluorine Moieties

A series of novel -aminophosphonates containing pyrazole and fluorine moieties was designed and synthesized through ultrasonic-assisted condensation and solvent-free addition reactions. Their structures were verified by IR, ^1H NMR, ^13C NMR and elemental analysis. The crystal structure of diethyl[（4-cyano-1H-pyrazol-3-ylamino）（3,5-difluorophenyl）methyl]phosphonate（4a, C15H17F2N4O3P） was determined by single-crystal X-ray diffraction. Compound 4a crystallizes in the triclinic system, space group P1 with a = 8.381（3）, b = 10.103（5）, c = 11.268（3） A, α= 83.772（19）, β= 74.726（19）, γ= 70.964（18）, V = 869.9（6） 3, Mr = 370.30, Dc = 1.414 g/cm^3, Z = 2, F（000） = 384, = 0.200 mm^-1, MoKa radiation（ = 0.71073 ）, the final R = 0.0487 and w R = 0.0823 for 1582 observed reflections with I 〉 2（I）. X-ray diffraction analysis reveals that there are two planes in 4a, and the dihedral angle is 71.51°. Two intermolecular hydrogen bonds and a face-to-face … stacking interaction are observed in the crystal structure. The compounds were evaluated for their antifungal, antiviral and antitumor activities, respectively. Among them, 4b, 4c, 4g and 4h exhibit good activities on Sclerotium rolfsii Sacc at 200 μg/m L, while 4b, 4c, 4f and 4g possess good anti-TMV activities at 500 μg/m L. Unfortunately, all of the compounds showed weak antitumor activities.

Synthesis, Crystal Structure and Bioactivities of 1-(4-Chlorophenyl)-3-[5-(pyrid-4-yl)-1,3,4-thiadiazol-2-yl]urea

The title compound 1-（4-chlorophenyl）-3-[5-（pyrid-4-yl）-1,3,4-thiadiazol-2-yl]urea （C14H10CIN5OS, Mr = 331.79） has been synthesized by the reaction of 2-amino-5-（pyrid-4-yl）- 1,3,4-thiadiazole with 4-chlorobenzoyl azide, and its crystal structure was determined by single-crystal X-ray diffraction. The crystal belongs to triclinic system, space group PI with a = 5.8550（8）, b = 7.5668（10）, c = 16.416（2）A, α= 78.364（2）, β= 81.204（2）, γ= 84.749（2）°, V= 702.58（16）A^3, Z= 2, Dc = 1.568 g/cm^3, p = 0.429 mm ^-1, F（000） = 340, the final R = 0.0442 and wR = 0.1092 for 2001 observed reflections （1 〉 2σ（I））. X-ray diffraction analysis reveals that the title molecule is nearly planar. In the crystal structure, the molecules are linked by strong intermolecular N-H…N hydrogen bonds together with weak nonclassical intennolccular （C-H…Y, Y = N, O and CI） hydrogen bonds and stacked through π-π interactions. The preliminary bioassay shows that the title compound exhibits good fungicidal activities against Rhizoctonia solani, Botrytis cinerea and Dothiorella gregaria.