Synthesis of N1-phenethyl substituted indole derivatives as new melatoninergic agonists and antagonists

The potency of new indolic N1-phenethyl substituted melatoninergic ligands with and without methyl groups in the alpha and beta position of the alkanamidoethyl side chain was examined using the pigment aggregation response in a clonal line of Xenopus laevis melanophores. The non 5-OMe substituted compounds, 8a--e, are all weak antagonists while introduction of the 5-OMe group, 9a--e, increases both agonist and antagonist activity except for 9c (R=C3H7), which is only an agonist and 9e (R=c-C4H7), which is only an antagonist. Introduction of an alpha-methyl group into the 5-OMe derivatives, 14a-e, reduces the agonist potency while introduction of a beta-methyl group has only a small effect on either the agonist or antagonist potency. Double beta-methyl substitution of the 5-OMe derivatives, 20a--e, generally increases the agonist potential (20c, R=C3H7 is the most potent agonist of the compounds described) and decreases the antagonist potency, except for 20a (R=CH3), which is the most potent antagonist of this series of compounds.     

Biological and Cheminformatics Studies of Newly Designed Triazole Based Derivatives as Potent Inhibitors against Mushroom Tyrosinase

A series of nine novel 1,2,4-triazole based compounds were synthesized through a multistep reaction pathway and their structures were scrutinized by using spectral methods such as FTIR, LC-MS, 1H NMR, and 13C NMR. The synthesized derivatives were screened for inhibitory activity against the mushroom tyrosinase and we found that all the synthesized compounds demonstrated decent inhibitory activity against tyrosinase. However, among the series of compounds, N-(4-fluorophenyl)-2-(5-(2-fluorophenyl)-4-(4-fluorophenyl)-4H-1,2,4-triazol-3-ylthio) acetamide exhibited more prominent activity when accompanied with the standard drug kojic acid. Furthermore, the molecular docking studies identified the interaction profile of all synthesized derivatives at the active site of tyrosinase. Based on these results, N-(4-fluorophenyl)-2-(5-(2-fluorophenyl)-4-(4-fluorophenyl)-4H-1,2,4-triazol-3-ylthio) acetamide could be used as a novel scaffold to design some new drugs against melanogenesis.     

Cyclopropane-based stereochemical diversity-oriented conformational restriction strategy: histamine H3 and/or H4 receptor ligands with the 2,3-methanobutane backbone

The stereochemical diversity-oriented conformational restriction strategy can be an efficient method for developing specific ligands for drug target proteins. To develop potent histamine H(3) and/or H(4) receptor ligands, a series of conformationally restricted analogs of histamine with a chiral trans- or cis-4-amino-2,3-methano-1-(1H-imidazol-4-yl)butane structure was designed based on this strategy. These stereochemically diverse compounds were synthesized from previously developed versatile chiral cyclopropane units. Among these analogs, a trans-cyclopropane-type compound, (2S,3R)-4-(4-chlorobenzylamino)-2,3-methano-1-(1H-imidazol-4-yl)butane (5b), has remarkable antagonistic activity to both the H(3) (K(i) = 4.4 nM) and H(4) (K(i) = 5.5 nM) receptors, and a cis-cyclopropane-type compound, (2R,3R)-4-amino-2,3-methano-1-(1H-imidazol-4-yl)butane (6a), is a potent and selective H(3) receptor partial agonist (K(i) = 5.4 nM). Although (2S,3R)-4-amino-2,3-methano-1-(1H-imidazol-4-yl)butane (5a) does not have a hydrophobic group which the usual H(3) receptor antagonists have, it was found to be a potent H(3) receptor antagonist (K(i) = 20.1 nM). Thus, a variety of compounds with different pharmacological properties depending on the cyclopropane backbones and also on the side-chain functional groups were identified. In addition to the previously used 1,2-methanobutane backbone, the 2,3-methanobutane backbone also worked effectively as a cyclopropane-based conformational restriction structure. Therefore, the combination of these two cyclopropane backbones increases the stereochemical and three-dimensional diversity of compounds in this strategy, which can provide a variety of useful compounds with different pharmacological properties.     

A Series of Analogues to the AT2R Prototype Antagonist C38 Allow Fine Tuning of the Previously Reported Antagonist Binding Mode

We here report on our continued studies of ligands binding to the promising drug target angiotensin II type 2 receptor (AT₂R). Two series of compounds were synthesized and investigated. The first series explored the effects of adding small substituents to the phenyl ring of the known selective nonpeptide AT₂R antagonist C38 , generating small but significant shifts in AT₂R affinity. One compound in the first series was equipotent to C38 and showed similar kinetic solubility, and stability in both human and mouse liver microsomes. The second series was comprised of new bicyclic derivatives, amongst which one ligand exhibited a five-fold improved affinity to AT₂R as compared to C38 . The majority of the compounds in the second series, including the most potent ligand, were inferior to C38 with regard to stability in both human and mouse microsomes. In contrast to our previously reported findings, ligands with shorter carbamate alkyl chains only demonstrated slightly improved stability in microsomes. Based on data presented herein, a more adequate, tentative model of the binding modes of ligand analogues to the prototype AT₂R antagonist C38 is proposed, as deduced from docking redefined by molecular dynamic simulations.     

Bioactive aromatic derivatives from endophytic fungus, Cytospora sp

Two new benzyl gamma-butyrolactone analogues, (R)-5-((S)-hydroxy(phenyl)-methyl)dihydrofuran-2(3H)-one (1) and its 6-acetate (2), and a new naphthalenone derivative (8), together with eight additional known aromatic derivatives, (S)-5-((S)-hydroxy(phenyl)-methyl)dihydrofuran-2(3H)-one (3), (S)-5-benzyl-dihydrofuran-2(3H)-one (4), 5-phenyl-4-oxopentanoic acid (5), gamma-oxo-benzenepentanoic acid methyl ester (6), 3-(2,5-dihydro-4-hydroxy-5-oxo-3-phenyl-2-furyl)propionic acid (7), (3R)-5-methylmellein (9), integracins A (10) and B (11) were isolated from Cytospora sp., an endophytic fungus isolated from Ilex canariensis from Gomera. The structures of these compounds were elucidated by detailed spectroscopic analysis, comparison with reported data, and chemical interconversion. The absolute configurations of the new compounds (1, 2, 8) were established on the basis of optical rotation or CD spectra analysis. Preliminary studies showed antimicrobial activity of these compounds against the fungi Microbotryum violaceum, Botrytis cinerea and Septoria tritici, the alga Chlorella fusca, and the bacterium Bacillus megaterium.     

Comparison of the structure and magnetic order in a series of layered Ni(II) organophosphonates, Ni[(RPO3)(H2O)] (R = C6H5, CH3, C18H37)

The reaction of nickel chloride with phenyl phosphonic acid under hydrothermal conditions resulted in the isolation of yellow-green single crystals of Ni[(C(6)H(5)PO(3))(H(2)O)]. The structure of the compound has been solved by X-ray single-crystal diffraction studies. Ni[(C(6)H(5)PO(3))(H(2)O)] crystallizes in the orthorhombic space group Pmn2(1) and is isostructural with the Mn(II), Fe(II), and Co(II) analogues. It presents the typical features of the hybrid 2D structures, consisting of alternating inorganic and organic layers. The former are formed by six-coordinated nickel(II) ions bridged by oxygen atoms into the layers. The inorganic layers are capped by the phenyl phosphonate groups, with phenyl groups of two adjacent ligands forming a hydrophobic bilayer region, and van der Waals contacts are established between them. The magnetic properties investigated by means of dc and ac susceptibility measurements point to an AF exchange coupling between nearest neighboring Ni(II) ions. Below 5 K, the compound orders magnetically showing the typical features of a canted antiferromagnet. The magnetic behavior and magnetic dimensionality of Ni[(C(6)H(5)PO(3))(H(2)O)] have been fully analyzed and compared to those of the Ni(II) parent compounds Ni[(RPO(3))(H(2)O)] (where R = CH(3), C(18)H(37)), which exhibit different symmetries of the inorganic layers and lengths of the R groups.     

Effect of S–Se Bioisosteric Exchange on Affinity and Intrinsic Efficacy of Novel N-acylhydrazone Derivatives at the Adenosine A2A Receptor

In this work, we evaluated the conformational effect promoted by the isosteric exchange of sulfur by selenium in the heteroaromatic ring of new N-acylhydrazone (NAH) derivatives (3–8, 13, 14), analogues of the cardioactive compounds LASSBio-294 (1) and LASSBio-785 (2). NMR spectra analysis demonstrated a chemical shift variation of the iminic Csp² of NAH S/Se-isosters, suggesting a stronger intramolecular chalcogen interaction for Se-derivatives. To investigate the pharmacological profile of these compounds at the adenosine A_2A receptor (A_2AR), we performed a previously validated functional binding assay. As expected for bioisosteres, the isosteric-S/Se replacement affected neither the affinity nor the intrinsic efficacy of our NAH derivatives (1–8). However, the N-methylated compounds (2, 6–8) presented a weak partial agonist profile at A_2AR, contrary to the non-methylated counterparts (1, 3–5), which appeared as weak inverse agonists. Additionally, retroisosterism between aromatic rings of NAH on S/Se-isosters mimicked the effect of the N-methylation on intrinsic efficacy at A_2AR, while meta-substitution in the phenyl ring of the acyl moiety did not. This study showed that the conformational effect of NAH-N-methylation and aromatic rings retroisosterism changed the intrinsic efficacy on A_2AR, indicating the S/Se-chalcogen effect to drive the conformational behavior of this series of NAH.     

Design, synthesis and anti-fibrosis activity study of N₁-substituted phenylhydroquinolinone derivatives

Pirfenidone (5-methyl-1-phenyl-2(1H)-pyridone, PFD) is a small-molecule compound acting on multiple targets involved in pathological fibrogenesis and is effective to increase the survival of patients with fibrosis, such as idiopathic pulmonary fibrosis. However, PFD is not active enough, requiring a high daily dose. In this study, to keep the multiple target profiles, N?-substituted phenylhydroquinolinone derivatives, which retain the 1-phenyl-2(1H)-pyridone scaffold were designed and synthesized. The preliminary anti-fibrosis activities for all target compounds were evaluated on a NIH3T3 fibroblast cell line using MTT assay methods. Most compounds showed significant inhibition on NIH3T3 cell proliferation with a IC?? range of 0.09-26 mM, among which 5-hydroxy-1-(4'-bromophenyl)-5,6,7,8-tetrahydroquinolin-2(1H)-one (6j) displayed 13 times higher potency (IC?? = 0.3 mM) than that of AKF-PD (IC?? = 4.2 mM). These results suggest that N?-substituted phenylhydroquinolinone is a promising scaffold which can be applied for further investigation and for developing novel anti-fibrosis agents.     

Rhenium diazenide ternary complexes with dithiocarbamate ligands: towards new rhenium radiopharmaceuticals

The reaction of the mono-diazenide core, [ReCl2(NNC6H(4)-4-OCH3)(NCCH3)(PPh3)2], with four equivalents of the sodium or potassium salts of dithiocarbamate (dtc) ligands gives neutral complexes of the formula [Re(NNC6H(4)-4-OCH3)(dtc)2(PPh3)]. It is possible to use a wide range of dithiocarbamate ligands (S2CNRR') with a variety of R groups (R=R'=methyl, phenyl or ethyl; R=methyl, R'=phenyl and R=R'=morpholino). Substitution reactions with dtc ligands on the mono-diazenide derived from 2-hydrazinopyridine, [ReCl2(NNC5H4N)(PPh3)2, give the analogous complexes, [Re(NNC6H5N)(dtc)2(PPh3)]. The new complexes have been characterised by a combination of NMR spectroscopy, mass spectrometry and X-ray crystallography. Cyclic voltammetry measurements in dimethyl formamide show that the rhenium diazenido-dtc complexes undergo a quasi-reversible oxidation tentatively assigned to a ReIII/ReIV oxidation. Since the parent complex, [ReCl2(NNC6H(4)-4-R)(NCCH3)(PPh3)2] can be prepared directly from perrhenate and readily derivatised with dtc ligands these complexes have potential relevance to the development of new therapeutic rhenium radiopharmaceuticals.     

新型含吡唑环的N-甲氧基氨基甲酸甲酯类化合物的设计、合成及生物活性

以苯(吡啶)乙/丙酮类化合物为原料, 经酯化、环化和缩合三步制得新型含吡唑环的N-甲氧基氨基甲酸甲酯类化合物3a~3r, 化合物及其中间体的化学结构经红外光谱、核磁共振谱及元素分析确认. 生物活性结果表明, 化合物3在400 mg/L下分别对水稻稻瘟病、黄瓜霜霉病和小麦白粉病具有很好的防治效果. 对水稻稻瘟病, R₁为甲基或甲氧基取代的苯基时活性最好; 对于黄瓜霜霉病和小麦白粉病, R₁为苯基或甲基取代苯基的化合物杀菌活性优于其它化合物, R₂为甲基的化合物杀菌活性优于R₂为氢的化合物.     

Siloxane-supported organometallic compounds and their catalytic activities for the hydrosilylation of vinylsilanes and dienes

Two different classes of silicone-modified ligands were prepared: nitrile derivatives, 4'-[3-(organosilyl)propoxy]biphenyl-4-carbonitrile R'3SiC3H6OC6H4C6H4CN (R'3Si- = a: Me3SiOSiMe2-, b: (Me(3)SiO)2SiMe-, c: Me3SiO(Me2SiO)3SiMe2-, d: Me3SiO(Me2SiO)25SiMe2-); and, pyridine derivatives, isonicotinic acid 2-methoxy-4-[3-(organosilyl)propyl]phenyl ester R'3SiC3H6Ph(O)MeOCOC5H4N . Compounds and were bound to Pd and Pt using ligand substitution reactions with organometallic precursors to give (R3SiC3H6OC6H4C6H4CN)2PdCl2, (R3SiC3H6OC6H4C6H4CN)2PtCl2 and (R3SiC3H6C6H3(OMe)OC(O)C5H4N)PtCl2(eta(2)-1-octene). The polydimethylsiloxane (PDMS)-supported Pt and Pd compounds and had excellent solubility in both organic solvents and polysiloxanes. All the Pt compounds exhibited good catalytic activity for hydrosilylation of vinylsilanes. The PDMS-supported Pd compound also was effective catalyst for hydrosilylation of a diene, isoprene, with 1,1,1,3,3-pentamethyldisiloxane MM(H) to produce the 1,4-adduct Me3SiOSiMe2CH2CH=CMeCH2-H as a major product.     

Synthesis and in vitro evaluation of iodinated derivatives of piperazine as a new ligand for sigma receptor imaging by single photon emission computed tomography

A new series of radioiodinated analogues of 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazine (SA4503) was synthesized and evaluated as a potential brain sigma-1 receptor imaging ligands by single photon emission computed tomography (SPECT). Iodinated analogues of SA4503 (4a-c) were prepared from piperazine in a high yield. The in vitro competition binding studies using [3H] DTG (sigma-1, 2), [3H] (+)-pentazocine (sigma-1), and [3H] DTG in the presence of carbetapentane (sigma-2) as sigma receptor selective radioligands were revealed that iodinated analogues 4a-c possess high affinities to sigma receptors (IC50: 4a=7.1, 4b=31.0, and 4c=77.3 nM). In particular, the affinity of 4a, bearing iodine at ortho position on the phenyl ring, was 4.4 times greater than SA4503, and 3 times greater than that of haloperidol. The meta-iodo analogue 4b was the same to SA4503, the lead compound. The radioiodinated derivatives, [125I] 4a, 4b were synthesized no-carrier-added from the corresponding tributyltin precursors by the iododestannylation reaction with high yields. The binding of [125I] 4a, 4b have been characterized in the rat brain membranes. These compounds were indicated single population binding to sigma receptor with high affinity (4a: Kd=1.86+/-0.34 nM, Bmax=205+/-28.9 fmol/mg protein, 4b: Kd=3.30+/-0.51 nM, Bmax=231.5+/-13.8 fmol/mg protein). In vitro blocking studies were confirmed that the high specificity of 4a, 4b. These results suggest that radioiodinated 4a and 4b are promising sigma receptors imaging ligand for pursuing further in vivo studies.     

Opioid ligands with mixed properties from substituted enantiomeric N-phenethyl-5-phenylmorphans. Synthesis of a micro-agonist delta-antagonist and delta-inverse agonists

Enantiomeric N-phenethyl-m-hydroxyphenylmorphans with various substituents in the ortho, meta or para positions of the aromatic ring in the phenethylamine side-chain (chloro, hydroxy, methoxy, nitro, methyl), as well as a pyridylethyl and a indolylethyl moiety on the nitrogen atom, were synthesized and their binding affinity to the mu-, delta-, and kappa-opioid receptors was examined. The higher affinity ligands were further examined in the [(35)S]GTPgammaS assay to study their function and efficacy. 3-((1R,5S)-(-)-2-(4-Nitrophenethyl)-2-aza-bicyclo[3.3.1]nonan-5-yl)phenol ((-)-) was found to be a mu-agonist and delta-antagonist in that functional assay and was about 50 fold more potent than morphine in vivo. 3-((1R,5S)-(-)-2-(4-Chlorophenethyl)-2-aza-bicyclo[3.3.1]nonan-5-yl)phenol ((-)-) and several other ligands displayed inverse agonist activity at the delta-opioid receptor. The absolute configuration of all of the reported compounds was established by chemical conversion of (-)- to 1R,5S-(-)-.HBr.     

Coordination behavior and biopotency of N and S/O donor ligands with their palladium(II) and platinum(II) complexes

Some metal complexes of Schiff bases have been prepared by the interactions of palladium(II) and platinum(II) chloride with 5-chloro-1,3-dihydro-3-[2-(phenyl)-ethylidene]-2H-indol-2-one-hydrazinecarbothioamide(L¹H) and 5-chloro-1,3-dihydro-3-[2-(phenyl)-ethylidene]-2H-indol-2-one-hydrazinecarboxamide(L²H), in bimolar ratios. All the new compounds have been characterized by elemental analyses, conductance measurements, molecular weight determinations, IR and ¹H NMR spectral studies. The spectral data are consistent with a square planar geometry around Pd(II) and Pt(II) in which the ligands act as neutral bidentate and monobasic bidentate ligands, coordinating through the nitrogen and sulfur/oxygen atoms. Free ligands and their metal complexes were screened for their antimicrobial activity on different species of pathogenic fungi and bacteria and their biopotency has been discussed.     

配合物稳定性与配体酸碱强度之间的直线自由能关系 XIII. N-(间位取代苯基)氨基乙酸，邻菲啰啉(α,'α-联吡啶)与镍(II),钴(II)和锌(II)生成三元配合物的稳定性研究

The formation constants of ternary mixed ligand complex compounds (logK_(MAB~(MA)) formed from 1,10-phenanthroline or 2,2'-bipyridyl (A), N-(meta-substituted phenyl) glycines, (B, m-RphG, R=CH_3, H, CH_3O, Cl) with Nickel(Ⅱ), Cobalt(Ⅱ) and Zinc(Ⅱ) were determined by pH method at 25 ℃ in 30% (Volume) ethanol solution in presence of 0.1 mol·dm~(-3) NaClO_4 or 0.1 mol·dm~(-3) KNO_3. It was found that linear free energy relationships exist between the stability of ternary complex compounds and the base strengths of ligands in all six ternary systems investigated. The stability of the ternary complex compounds was discused in terms of ΔlogK_M values and HSAB theory. It was found that linear relationships also exist between ΔlogK_M and pK_2 in the Ni(II)-phen-m-RPhG ternary system.     

Novel pincer complexes of Ag(I), coordination of toluene and their comparison with indium analogues

The bis(imino)pyridine scaffold provides for the synthesis and characterization of the unique Ag(I) pincer complexes [{ArN=CPh}(2)(NPh)]Ag(+)(OTf)(-) (Ar = 2,5-(t)Bu(2)C(6)H(3); 2,6-(i)Pr(2)C(6)H(3)). The similar covalent radii of Ag(I) and In(I), prompted a bonding comparison of these species with their In(I) analogues. Coordination of toluene to the Ag center revealed the stronger Lewis acidity of the metal site in these compounds relative to In(I) analogues.     

Structure-property relationships of fluorinated donor/acceptor tetrakis(phenylethynyl)benzenes and bis(dehydrobenzoannuleno)benzenes

Nine new bisdonor/bisacceptor-functionalized tetrakis(phenylethynyl)benzene (TPEB) and six new bis(dehydrobenzoannuleno)benzene (DBA) chromophores have been synthesized. The compounds consist of electron-donating dibutylaniline groups connected through a conjugated phenyl-acetylene scaffold to benzotrifluoride, bis(trifluoromethyl)phenyl, or pentafluorophenyl acceptor groups. In comparison to previously reported analogues utilizing nitrophenyl or benzonitrile acceptor groups, the weaker acceptor groups exhibit visibly fluorescent intramolecular charge transfer (ICT) behavior, moderately narrow optical band gaps, moderately high quantum yields, and strong fluorescence solvatochromism. In this series of molecules, the strongly inductive fluoro acceptor groups result in optical properties similar to the resonance acceptor analogues, making them promising candidates for optical materials device components. The data also support recent investigations that question the utility of using UV/vis spectroscopy alone as a qualitative measure of conjugation. The bisDBAs exhibit weaker ICT behavior and self-association in solution than their corresponding nitro analogues, but show greater stability to decomposition via polymerization and smaller optical band gaps than their acyclic analogues.     

多功能光学活性丁二醇衍生物的合成和结构

通过新的合成策略,以手性合成子3和具有生物活性的有机碱类化合物4为反应底物,利用Michael不对称加成反应,合成得到光学纯的5-(R)-［(1R,2S,5R)-(-)-氧基］-4-(R)-(杂环碱基)-2(5H)-呋喃酮(5). 加成物5通过还原反应得到了多功能光学活性的二醇类化合物6,产率为42%~82%,e.e.≥98%. 化合物6的化学结构得到了确认,其立体化学结构和绝对构型经X射线晶体学测定得到了确定.     

Diimine-acetylide compounds of ruthenium: the structural and spectroscopic effects of oxidation

The reaction of Ru(Me(2)bipy)(PPh(3))(2)Cl(2) 1 with terminal alkynes HCCR in the presence of TlPF(6) leads to the formation of the vinylidene compounds [Ru(Me(2)bipy)(PPh(3))(2)Cl(=C=CHR)][PF(6)] (2) (2a, R = Bu(t); 2b, R = p-C(6)H(4)-Me; 2c, R = Ph). These compounds decompose in oxygenated solution to form the carbonyl compound [Ru(Me(2)bipy)(PPh(3))(2)Cl(CO)][PF(6)] (3), and may be deprotonated by K(2)CO(3) to give the ruthenium(II) terminal acetylide compounds Ru(Me(2)bipy)(PPh(3))(2)Cl(CC-R) (4) (4a, R = Bu(t); 4b, R = p-C(6)H(4)-Me; 4c, R = Ph). Cyclic voltammetry shows that 2a-c may also be reductively dehydrogenated to form 4a-c. 4a-c are readily oxidized to their ruthenium(III) analogues [4a](+)-[4c](+), and the changes seen in their UV/visible spectra upon performing this oxidation are analyzed. These show that whereas the UV/visible spectra of 4a-c show MLCT bands from the ruthenium atom to the bipyridyl ligand, those of [4a](+)-[4c](+) contain LMCT bands originating on the acetylide ligands. This is in agreement with the IR and ESR spectra of [4a](+)-[4c](+). The X-ray crystal structures of the redox pair 4a and [4a][PF(6)()] have been determined, allowing the bonding within the metal-acetylide unit to be analyzed, and an attempt is made to determine Lever electrochemical parameters (E(L)) for the vinylidene and acetylide ligands seen herein. Room temperature luminescence measurements on 4a-c show that the compounds are not strongly emissive.     

Synthesis and in-vitro-antibacterial activity of [5-(furan-2-yl)-phenyl]-4,5-carbothioamide-pyrazolines

Cyclization of various different alkoxy [1-[2-(alkoxy)phenyl]-5-(furan-2-yl)-prop-2-en-1-one] chalcone with thiosemicarbazide in the presence of NaOH in ethanol afforded a series of novel 1-N-substituted cyclized pyrazoline analogues [5-(furan-2-yl)-3-[2-(alkoxy) phenyl]-4,5-dihydro-1H-pyrazole-1-carbothioamide 2a–2d. The structures of these compounds were elucidated by IR, ¹H NMR, ¹³C NMR, Fab mass spectrometry and their purities were confirmed by elemental analyses. In vitro antibacterial activity of these compounds were evaluated by the disk diffusion assay and then the minimum inhibitory concentration (MIC) strain of two Gram-positive and two Gram-negative bacteria like Aeromonas hydrophila, Yersinia enterocolitica, Listeria monocytogenes, and Staphylococcus aureus, among all the compounds, alkoxy [5-(furan-2-yl)-2-(benzyloxy)phenyl]-4,5-dihydro-1H-pyrazole-1-carbothioamide 2b and 5-(furan-2-yl)-1-[2-(naphthalen-2-ylmethoxy) phenyl]-4,5-dihydro-1H-pyrazole-1-carbothioamide 2d showed the most promising antibacterial agent when compared to gentamicin and tetracycline.