SYNTHESIS AND REACTVITY OF N-[N-PHOSPHORAMIDO-1H-BENZIMIDAZOL-2-YL] IMIDATES

N-(-1H-Benzimidazol-2-yl) imidates 1a–c react with chlorophosphoramide to give the N-[-1-N,N,N′,N′-tetramethylphosphoramidoyl-1H-benzimidazol-2-yl]-imidates 2a–c or with dichlorophosphoramide to yield the bis[(N-1-benzimidazol-2-yl)-imidate] phosphoramide derivatives 3a–b. The reaction of compounds 2a–c toward primary amines is studied. The obtained amidine derivatives 4a–b were unambiguously characterized by different spectroscopic techniques (IR, ¹H, ¹³C, and ³¹P NMR, and in some cases MS).     

N-(4-哌啶基)苯甲酰胺衍生物的设计、合成及其抗肝癌活性

以4-羟基苯甲酸乙酯为原料,经烃化、水解、缩合、脱保护、磺酰化反应,合成了6个含有磺酰基取代的4-苯氧基-N-(4-哌啶基)苯甲酰胺衍生物。 其结构经¹H NMR、¹³C NMR和MS谱等技术手段进行了表征,并以索拉非尼为阳性对照药对HepG2细胞株进行了初步体外抗肝癌细胞增殖活性的评价。 实验发现,4-苯氧基-N-(1-甲磺酰基哌啶-4-基)苯甲酰胺的体外抗肝癌生物活性优于索拉非尼,IC₅₀值为8.42 μmol/L。 研究结果表明,新结构4-苯氧基-N-(4-哌啶基)苯甲酰胺类化合物具有良好的抗肝癌活性。     

Synthesis of 7-azabicyclo[2.2.1]heptane and 2-oxa-4-azabicyclo[3.3.1]non-3-ene derivatives by base-promoted heterocyclization of alkyl N-(cis(trans)-3,trans(cis)-4-dibromocyclohex-1-yl)carbamates and N-(cis(trans)-3,trans(cis)-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamides

We have studied the base-promoted heterocyclization of alkyl N-(cis(trans)-3,trans(cis)-4-dibromocyclohex-1-yl)carbamates and N-(cis(trans)-3,trans(cis)-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamides, investigating the effect of the nitrogen protecting group and the relative configuration of the leaving group at C3 and C4 on the outcome of this reaction. We have observed that the sodium hydride-promoted heterocyclization of alkyl N-(cis-3,trans-4-dibromocyclohex-1-yl)carbamates (10, 12, 14, 16, 18) is a convenient method for the synthesis of 7-azabicyclo[2.2.1]heptane derivatives. For instance, the reaction of tert-butyl N-(cis-3,trans-4-dibromocyclohex-1-yl)carbamate (10) with sodium hydride in DMF at room temperature provides 2-bromo-7-[(tert-butoxy)carbonyl]-7-azabicyclo[2.2.1]heptane (2) (52% yield), whose t-BuOK-promoted hydrogen bromide elimination affords 7-[(tert-butoxy)carbonyl]-7-azabicyclo[2.2.1]hept-2-ene (31) in 78% yield, an intermediate in the total synthesis of epibatidine (1). However, the NaH/DMF-mediated heterocyclization of alkyl N-(trans-3,cis-4-dibromocyclohex-1-yl)carbamates (11, 13) is a more structure dependent reaction, where the nucleophilic attack of the oxygen atom of the protecting group controls the outcome of the reaction, giving rise to benzooxazolone and 2-oxa-4-azabicyclo[3.3.1]non-3-ene derivatives, respectively, from low to moderate yields, in complex reaction mixtures. Conversely, the NaH/DMF heterocyclizations of N-(cis-3,trans-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamide (40) or N-(trans-3,cis-4-dibromocyclohex-1-yl)-2,2,2-trifluoroacetamide (42) are very clean reactions giving 7-azabicyclo[2.2.1]heptane or 2-oxa-4-azabicyclo[3.3.1]non-3-ene derivatives, respectively, in good yields. Finally, a mechanistic investigation, based on DFT calculations, has been carried out to rationalize the formation of the different adducts.     

N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)酰胺类新化合物的合成及生物活性

以N-吡啶基吡唑甲酸和2-氨基-3-甲基苯甲酸为起始原料,经由亲核加成、环化和酰化等多步反应合成了一系列结构新颖的N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)酰胺类化合物.测试了所合成化合物的杀虫及抑菌活性,结果表明,新化合物大多化合物在200 mg·L^-1浓度下对东方粘虫(Mythimna separataWalker)具有一定的杀虫活性,尤其是N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)乙酰胺(8a)和N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)-3-氯-2,2-二甲基丙酰胺(8e)致死率可达70%;部分化合物在50 mg·L^-1浓度下对油菜菌核病菌的抑菌活性相对较好(54.5%~63.6%),优于triadimefon和chlorantraniliprole;部分化合物如N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)-3,3-二甲基丁酰胺80和N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)-4-氟苯甲酰胺(8h)对苹果轮纹病菌具有中等抑菌活性.值得注意的是,化合物8e的杀粘虫活性和对油菜菌核病菌的抑菌活性都较为突出,可用作新农药创制研究的新型参考结构.     

Novel approach to aminocarboranes by mild amidation of selected iodo-carboranes

A mild protocol for the palladium-catalyzed Buchwald-Hartwig amidation of icosahedral carboranes is described. Employing 2-dicyclohexylphosphino-2'-(N,N-dimethylamino)biphenyl (1) as a ligand and K(3)PO(4) as a base, benzamide, trifluoroacetamide, acetamide, and formamide were coupled to a series of mono- and di-iodo carboranes furnishing the respective carborane derivatives in good to excellent yields. Subsequent base-mediated saponification of the trifluoroacetamide derivatives was shown to provide the free aminocarboranes. The structures of N-(1,7-dicarba-closo-dodecaboran-9-yl)benzamide (8a), N-(1,7-dicarba-closo-dodecaboran-9-yl)trifluoroacetamide (8b), N-(1,12-dicarba-closo-dodecaboran-2-yl)benzamide (10a), N-(1,2-dicarba-closo-dodecaboran-9-yl)benzamide (12a), N-(1,2-dicarba-closo-dodecaboran-9-yl)acetamide (12c), N-(1,2-dicarba-closo-dodecaboran-9-yl)formamide (12d), N-(1,2-dicarba-closo-dodecaboran-3-yl)benzamide (13a), N,N'-(1,7-dicarba-closo-dodecaboran-9,10-diyl)dibenzamide (15a), and N,N'-(1,7-dicarba-closo-dodecaboran-9,10-diyl)bis(trifluoroacetamide) (15b) have been established through X-ray single-crystal diffraction studies.     

An efficient one-pot three-component synthesis and antimicrobial evaluation of tetra substituted thiophene derivatives

A convenient one-pot three-component method for the preparation of tetra-substituted thiophene derivatives has been developed. Reaction of acetyl acetone 1, phenyl isothiocynate 2 and 2-chloromethyl derivatives 3a–3c in the presence of potassium carbonate afforded the target compounds, namely ethyl2-(4-acetyl-3-methyl-5-(phenylamino)thiophen-2-yl)-2-oxoacetate derivatives 4a–4e, ethyl 3-(4-acetyl-3-methyl-5-(phenylamino)thiophen-2-yl)-3-oxopropanoate derivatives 4f–4i, di((4-acetyl-3-methyl-5-phenylamino)thiophen-2-yl)ketone derivatives 4j–4n in reasonable overall yields. The synthesized compounds were screened for antimicrobial activity. The detailed synthesis, spectroscopic data and antimicrobial activities of synthesized compounds were reported.     

Synthesis and Some Chemical Behaviour of Certain Substituted Thiosemicarbazides

Three new thiosemicarbazides (1 a-c ) were prepared from N-[4-phenyl-5-(2-thienyl)-1,2,4-triazol-3-yl]mercaptoacetohydrazide. Reaction of (1 a-c) with the appropriate phenacyl bromide afforded thiazoline derivatives (2 a-i) whereas their reaction with chloroacetic acid or maleic anhydride gave the corresponding thiazolidine derivatives (3 a,b) and (4 a,b) . Cyclodesulfurization of (1 a-c) with DCCD in toluene yielded 5-substituted-amino-1,3,4-oxadiazoles (5 a,b) , while their dehydration with PPA gave the corresponding 5-substituted-amino-1,3,4-thiadiazoles (6 a-c) . Six representative compounds were tested for their in-vitro antimicrobial activity against some pathogenic microorganisms, some of them were proved to be active.     

N-(安替比林-4-基)-N'-取代芳甲酰基硫脲的合成及其生物活性

合成了12个含安替比林基的取代芳甲酰基硫脲类化合物,用1H NMR,IR和元素分析确证了它们的结构,并进行了室内生物活性测试.生测实验证明部分酰基硫脲类化合物,比如N-(安替比林-4-基)-N'-m(或o)-甲苯甲酰基硫脲,N-(安替比林-4-基)-N-o-硝基苯甲酰基硫脲,N-(安替比林-4-基)-N'-m(或p)-氯苯甲酰基硫脲,具有一定的细胞分裂素活性.     

Synthesis and antibacterial activity of new N-[2-(thiophen-3-yl)ethyl] piperazinyl quinolones

As a part of continuing search for potential antibacterial agents in the quinolones field, we have synthesized novel quinolone agents bearing N-[2-(thiophen-3-yl)ethyl] piperazinyl moiety in the 7-position of the quinolone ring. In vitro antibacterial evaluation of the target compounds showed that N-[2-(thiophen-3-yl)ethyl] group attached to piperazine ring served as promising C-7 substituent for piperazinyl quinolone antibacterials. Among these derivatives, ciprofloxacin analogues, containing N-[2-(thiophen-3-yl)-2-hydroxyiminoethyl] or N-[2-(thiophen-3-yl)-2-methoxyiminoethyl] residue provided a high inhibition against all the tested Gram-positive organisms including methicillin-resistant Staphylococcus aureus comparable or superior with respect to the reference drugs norfloxacin and ciprofloxacin.     

Lithium, titanium, and zirconium complexes with novel amidinate scorpionate ligands

The reaction of bis(3,5-dimethylpyrazol-1-yl)methane (bdmpzm) with BunLi and carbodiimide derivatives, namely, N,N'-diisopropyl, dicyclohexyl, and 1-tert-butyl-3-ethyl carbodiimides, enables the preparation of new heteroscorpionate ligands in the form of the lithium derivatives [Li(NNN)(THF)] (NNN = pbpamd (1) (pbpamd = N,N'-diisopropylbis(3,5-dimethylpyrazol-1-yl)acetamidinate); cbpamd (2) (cbpamd = N,N'-dicyclohexylbis(3,5-dimethylpyrazol-1-yl)acetamidinate); and tbpamd (3) (tbpamd = N-ethyl-N'-tert-butylbis(3,5-dimethylpyrazol-1-yl)acetamidinate)), although a similar process with N,N'-dimethylcarbodiimide gave the dinuclear complex [Li(bpzii)(THF)]2 (4) (bpzii = N-(dimethylamino)-N'-[(dimethylamino)bis(3,5-dimethylpyrazol-1-yl)methylimino]imino). When this last reaction was carried out in an air atmosphere, the cluster complex [Li8(mu4-O)2(mu4-OH)2(mu4-pz)2(kappa2-bpziLi)2(bpzCN)2(THF)4] (5) (bpziLi = dimethylaminobis(3,5-dimethylpyrazol-1-yl)methyliminolithium, bpzCN = bis(3,5-dimethylpyrazol-1-yl)acetonitrile) was isolated and characterized by X-ray analysis. Finally, when the same process was carried out in the presence of water the amidine-scorpionate (bpzan) (6) (bpzan = N,N-dimethylbis(3,5-dimethylpyrazol-1-yl)acetamidine) was obtained. Compounds 1 and 3 reacted with [TiCl4(THF)2] or [ZrCl4] to give complexes of stoichiometry [MCl3((kappa3-NNN))] (M = Ti, Zr) (7-10). The structures of the different compounds were determined by spectroscopic methods and, in addition, the X-ray crystal structures of 1, 3, 4, 5, and 6 were also established.     

新型他克林-吲哚杂二联体的微波促进Husigen[3+2]环加成反应合成及生物活性

以吲哚-3-丙酸和吲哚-3-丁酸为原料,分别与炔丙胺发生缩合反应得到3-(丙酰丙炔胺)吲哚(4a)和3-(丁酰丙炔胺)吲哚(4b),然后4a和4b分别与9-(叠氮基乙基氨基)-1,2,3,4-四氢吖啶类衍生物5a～5c在微波辐射下发生Husigen[3+2]环加成反应得到12个新型乙酰胆碱酯酶抑制剂——他克林-吲哚杂二联体,其结构经NMR,IR和HRMS表征.初步生物活性测试表明,目标化合物均具有较强的乙酰胆碱酯酶抑制能力,其中化合物2b和2d抑制鱼鳐乙酰胆碱酯酶的IC50值分别为1.6和2.0 nmol.L-1,是6T6BA(IC50=11.0 nmol.L-1,鱼鳐)的6.9和5.5倍.     

新型含哌嗪1,3,4-噻二唑酰胺衍生物的合成及其生物活性

以氨基硫脲和二硫化碳为起始原料,合成了15个新型的1,3,4-噻二唑衍生物(6a~6o),其结构经¹H NMR,¹³C NMR,IR,ESI-MS和元素分析表征。生物活性测试结果表明：大部分化合物对水稻白叶枯细菌有良好的抑制活性,其中,N-［5-(2,4-二氯苄基)硫醚］-1,3,4-噻二唑-2-(2-N-甲基哌嗪)-乙酰胺(6b)和N-［5-(4-三氟甲氧基苄基)硫醚］-1,3,4-噻二唑-2-(2-N-甲基哌嗪)-乙酰胺(6e)的EC₅₀分别为17.5 μg·mL^-1和19.8 μg·mL^-1; N-[5-(3-甲基苄基)硫醚)-1,3,4-噻二唑-2-(2-哌嗪)-乙酰胺(6k)在浓度为500 μg·mL^-1时,对烟草花叶病毒有一定的抑制活性。     

Synthesis of New 4,5-Dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-amine–Derived Ureas and Their Anticancer Activity

A new series of 1,2,4-triazolo[4,3-a]-quinoline derivatives were designed and synthesized to meet the structural requirements essential for anticancer activity. N-1-(5-Methylisoxazol-4-yl/4-fluoro-2,3-dihydro-1H-inden-1-yl/aryl)-N’-3-(4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-yl) urea derivatives were accomplished in good yields by the reaction of 4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-amine with 3-(3-chloro-5-fluoro-2-methoxyphenyl)-5-methyl-isoxazole-4-carboxylic acid, 4-fluoro-2,3-dihydro-1H-indene-1-carboxylic acid, and various simple aromatic carboxylic acids in the presence of diphenyl phosphoryl azide (DPPA). All the newly synthesized title compounds were characterized by elemental and spectral data. Furthermore, anticancer activity was screened for the title compounds (12a–j) in vitro against human neuroblastoma cell lines (SK N SH) and human colon carcinoma cell lines (COLO 205) by using the MTT cell viability method. A few of them (12a and 12b) possess significant cytotoxicity, and some other compounds 12d-f and 12j displayed moderate cytotoxicity against both cell lines.     

In vitro cytotoxicity activity on several cancer cell lines of acridone alkaloids and N-phenylethyl-benzamide derivatives from Swinglea glutinosa (Bl.) Merr

The methanol extract from the stems and fruits of Swinglea glutinosa (Rutaceae) afforded 11 known acridone alkaloids and three N-phenylethyl-benzamide derivatives, glycocitrine-IV, 1,3,5-trihydroxy-4-methoxy-10-methyl-2,8-bis(3-methylbut-2-enyl)acridin-9(10H)-one, 1,3,5- trihydroxy-2,8-bis(3-methylbut-2-enyl)-10-methyl-9-acridone, citbrasine, citrusinine-II, citrusinine-I, 5-dihydroxyacronycine, pyranofoline, 3,4-dihydro-3,5,8-trihydroxy-6-methoxy-2,2,7-trimethyl-2H-pyrano[2,3-a]acridin-12(7H)-one, 2,3-dihydro-4,9-dihydroxy-2-(2-hydroxy-propan-2-yl)-11-methoxy-10-methylfuro[3,2-b]acridin-5(10H)-one, bis-5-hydroxyacronycine, N-(2-{4-[(3,7-dimethylocta-2,6-dien-1-yl)oxy]phenyl}ethyl)benzamide, N-(2-{4-[(3,7-dimethyl-4-acethyl-octa-2,6-dien-1-yl)oxy]phenyl}ethyl)benzamide, and severine acetate. All compounds isolated were examined for their activity against three cancer cell lines: human lung carcinoma (COR-L23), human breast adenocarcinoma (MCF7), human melanoma (C32), and normal human fetal lung cell line, MRC-5. The acridones tested exhibited weak cytotoxicity but the amides showed moderate nonselective cytotoxic activity.     

N-{4-{N-甲基-N-[2-羟基-3-(2,4-二氧代-1,2,3,4-四氢嘧啶-5-基)氨基]丙基}氨基-3-溴}苯甲酰基-L-谷氨酸二乙酯及其衍生物的合成

报道了N-{4-{N-甲基-N-[2-羟基-3-(2,4-二氧代-1,2,3,4-四氢嘧啶-5-基)氨基]丙基}氨基-3-溴}苯甲酰基-L-谷氨酸二乙酯及其衍生物的简便合成方法. 分别以4-氨基苯甲酸乙酯和4-氨基苯甲酰基-L-谷氨酸二乙酯为起始物, 经甲基化、烯丙基化、溴羟基化、环氧化、开环、脱保护等反应首次合成了6个新型5-取代氨基嘧啶类化合物, 并通过¹H NMR, ¹³C NMR 和MS对其化学结构进行了表征. 初步生物活性结果表明, 苯环侧链的L-谷氨酸酯部分是此类化合物抑制人重组二氢叶酸还原酶的必需结构.     

Synthesis of 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane, 2-(pyridin-3-yl)-1-azabicyclo[2.2.2]octane, and 2-(pyridin-3-yl)-1-azabicyclo[3.2.1]octane, a class of potent nicotinic acetylcholine receptor-ligands

In an attempt to generate nicotinic acetylcholine receptor (nAChR) ligands selective for the alpha4beta2 and alpha7 subtype receptors we designed and synthesized constrained versions of anabasine, a naturally occurring nAChR ligand. 2-(Pyridin-3-yl)-1-azabicyclo[2.2.2]octane, 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane, and several of their derivatives have been synthesized in both an enantioselective and a racemic manner utilizing the same basic synthetic approach. For the racemic synthesis, alkylation of N-(diphenylmethylene)-1-(pyridin-3-yl)methanamine with the appropriate bromoalkyltetrahydropyran gave intermediates which were readily elaborated into 2-(pyridin-3-yl)-1-azabicyclo[2.2.2]octane and 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane via a ring opening/aminocyclization sequence. An alternate synthesis of 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane via the alkylation of N-(1-(pyridin-3-ylethylidene)propan-2-amine has also been achieved. The enantioselective syntheses followed the same general scheme, but utilized imines derived from (+)- and (-)-2-hydroxy-3-pinanone. Chiral HPLC shows that the desired compounds were synthesized in >99.5% ee. X-ray crystallography was subsequently used to unambiguously characterize these stereochemically pure nAChR ligands. All compounds synthesized exhibited high affinity for the alpha4beta2 nAChR subtype ( K i < or = 0.5-15 nM), a subset bound with high affinity for the alpha7 receptor subtype ( K i < or = 110 nM), selectivity over the alpha3beta4 (ganglion) receptor subtype was seen within the 2-(pyridin-3-yl)-1-azabicyclo[2.2.2]octane series and for the muscle (alpha1betagammadelta) subtype in the 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane series.     

4-(5-喹啉-3-基-四氮唑-2-基)丁胺的合成

三苯基膦钯催化3-溴喹啉完成氰化取代制得3-氰喹啉(1);1与叠氮化钠经[2+3]环加成合成了3-(2H-四氮唑-5-基)喹啉(2);2与N-(4-溴丁基)邻苯二甲酰亚胺反应制得2-[4-(5-喹啉-3-基-四氮唑-2-基)丁基]异吲哚-1,3-二酮(3);3经肼解合成了4-(5-喹啉-3-基-四氮唑-2-基)丁胺(4...     

N-苄氧/烷氧苯基-4,6-二取代嘧啶胺类化合物的合成、晶体结构及除草活性

以5种苄氧基/烷氧基苯胺为基础, 设计合成了系列新颖的N-苄氧/烷氧苯基-4,6-二取代嘧啶胺类化合物, 其结构经1H NMR、MS及元素分析确证, 其中化合物5r的单晶结构经X射线单晶衍射分析确证. 油菜平皿法和稗草小杯法测试除草活性结果表明, 4种苄氧基/烷氧基苯胺3a, 3b, 3d, 3e具有较好的除草活性, 在100 μg/mL浓度下对单子叶稗草生长抑制率可达到77.3%—88.5%. KARI活性测试结果表明, 化合物5a—5s有较弱的KARI抑制活性.     

Synthesis of certain alkenyl purines and purine analogs

Synthesis of alkenyl derivatives of certain purines and purine analogs is described. Direct alkylation of the sodium salt of 6-chloropurine (1) either with 1-bromo-2-pentene or 4-bromo-2-methyl-2-butene in N,N-dimethylformamide furnished N-7, 4a and N-9, 3a , 3b alkenyl derivatives. Similar alkylation of 2-amino-6-chloropurine (2) provided the corresponding N-7, 4c-4e and N-9, 3c-3e alkenyl derivatives. Acid hydrolysis of these chloro derivatives 3a-3e, 4a,c-e furnished the corresponding alkenyl hypoxan-thines 6a, 6b and 7a or alkenyl guanines 6c-6e and 7c-7e. Treatment of 3a-3d with thiourea in absolute ethanol provided the corresponding 6-thio derivatives 5a-5d. Alkylation of the sodium salt of either purine-6-carboxamide (8) or 1,2,4-triazole-3-carboxamide (10) gave mainly one isomer 9a, 9b and 11a, 11b. The direct alkylation of pyrrolo[2,3-d]pyrimidin-4(3H)-one (12) gave N-3 alkenyl derivatives 13a, 13b , and the N-7 alkenyl derivatives 16a, 16b have been prepared starting from the 4-chloro derivative 14 . Synthesis of 2-amino-7-(2-penten-1-yl)pyrrolo[2,3-d]pyrimidin-4(3H)-one (19a) has been accomplished starting from 2-amino-4-methoxypyrrolo[2,3-d]pyrimidine (17) . These alkenyl derivatives were found to be devoid of anti-HCMV activity in vitro.     

Ultrasound-assisted synthesis and anticancer evaluation of new pyrazole derivatives as cell cycle inhibitors

We designed new pyrazole derivatives as inhibitors of the cell cycle kinases and developed a simple environmentally sustainable synthesis process. We synthesized the pyrazolyl thiourea derivatives using rapid ultrasound mediated methods and confirmed their structures by NMR and IR spectra. The apoptosis and necrosis inducing effects of the new compounds were investigated. Cell cycle analysis and expression of genes involved in apoptosis, cell cycle and xenobiotic metabolism were studied. The compounds presented modest apoptotic effects in human cancer cells. The N-[[3-(4-bromophenyl)-1H-pyrazol-5-yl]carbamothioyl]-4-chloro-benzamide compound (4e) induced a significant increase of cells in G2/M phases in conjunction with an increased expression of cyclin A and cyclin B, emerging as a promising anticancer drug, to be further developed in animal models of cancer.