Synthesis and biological evaluation of several 3‐(coumarin‐4‐yl)tetrahydroisoxazole and 3‐(coumarin‐4‐yl)dihydropyrazole derivatives

A series of novel 3‐(coumarin‐4‐yl)tetrahydroisoxazoles 5a,b, 7, 9 and 3‐(coumarin‐4‐yl)dihydropyra‐zoles 13a‐d, 14,15a,b were synthesized from coumarin‐4‐carboxaldehyde 1 via the intermediate N‐methyl nitrone 3 and N‐phenyl or N‐methyl hydrazones 11a,b . These coumarin derivatives were isolated, characterized and evaluated in vitro for their ability to inhibit trypsin, β‐glucuronidase, soybean lipoxygenase and to interact with the stable radical 1,1‐diphenyl‐2‐picrylhydrazyl. The compounds were tested in vivo as anti‐inflammatory agents in the rat carrageenin paw edema assay. Compound 15a seems to be a lead molecule to be modified in order to improve the lipoxygenase inhibition. The results are discussed in terms of structural characteristics.     

Synthesis and biological activity research of novel ferrocenyl-containing thiazole imine derivatives

A series of novel N-substituted benzylidene-4-ferrocenyl-5-(1H-1,2,4-triazol-1-yl)-1,3-thiazol-2-amine derivatives were synthesized by condensation of substituted-benzaldehydes with 2-amino-4-ferrocenyl-5-(1H-1,2,4-triazol-1-yl)-1,3-thiazole and characterized by ¹H NMR, X-ray diffraction and elemental analysis. The results of bioassay showed that some title compounds exhibited some degree of plant growth regulatory and antifungal activities.     

Synthesis and biological evaluation of novel methylene‐bis‐[1,5]‐benzodiazepines

A series of novel methylene‐bis‐chalcones 3 was prepared by the reaction of 5‐(3‐formyl‐4‐hydroxybenzyl)‐2‐hydroxy benzaldehyde 2 with different acetophenones, subsequent treatment of compound 3 with an appropriate o‐phenylenediamine gave the corresponding methylene‐bis‐[1,5]‐benzodiazepines 4/5 in good yields. Characterization of the new compounds has been done by means of IR, ¹H NMR, MS and elemental analyses. The antibacterial and antifungal activity of the compounds has also been evaluated.     

Synthesis of some novel pyrazoline‐thiazole hybrids and their antimicrobial activities

A series of novel thiazolyl pyrazolines 7a‐h , 9a‐f , and 11a‐f have been synthesized by the reaction of thioamide derivatives 5a , b with 1‐aryl‐2‐bromoethanones 6a‐d , chloroacetones 8a‐c , and hydrazonoyl chlorides 10a‐c . Additionally, pyrazoles 15a‐c and 20 were prepared starting from enaminone 13 . These newly synthesized compounds were screened for their in vitro antibacterial activity against four bacterial species. Compound 11b showed a moderate activity against Klebsiella pneumoniae. Compounds 7c and 11c revealed a moderate activity against Pseudomonas aeruginosa. In addition, the antifungal activity of the newly synthesized compounds was determined against five fungal strains. Compounds 7e , 7g , and 11e showed a good activity against Aspergillus flavus and Penicillium expansum.     

π‐Aryl/heteroaryl conjugated coumarin‐thiazoles: Synthesis,optical spectral and nonlinear optic properties

A series of π‐aryl/heteroaryl conjugated coumarin‐thiazole systems 8a‐f has been synthesized by using Hantzsch thiazole protocol and Wittig olefination as the keys. In the UV‐Visible spectra of 8a‐f , a main absorption band associated with a dominant π‐π* transition is observed in the region of 338 to 390 nm. Qualitatively, the values of λ_max have been found to correlate satisfactory with the donor/acceptor characteristics of the π‐attached chromophores. Marked changes observed in the absorption maxima of 8a under acidic conditions are rationalized on the basis of mono‐or bis‐protonation and modification of the donor/acceptor properties of chromophores undergoing protonation. The emission spectra of 8a‐f , obtained by exciting the molecules at their main absorption bands showed emission maxima in the region of 429 nm to 537 nm, with relatively high Stokes shifts of 145 and 171 nm being observed for 8a and 8e , carrying a π‐donor, dimethylaminophenyl and a π‐acceptor, p‐nitrophenyl chromophore, respectively. Although, the first hyperpolarisability β, measured by the hyper‐Reileigh scattering (HRS) technique are modest (12 to 23 × 10^?30 esu), all the compounds exhibited complete transparency in the frequency doubling region at 532 nm and showed high thermal stability (T_d from 330 to 365 °C).     

Synthesis and evaluation of new pyrazoline‐thiazole derivatives as monoamine oxidase inhibitors

A novel series of 1,3,5‐trisubstituted‐2‐pyrazoline derivatives ( 4a ‐ 4k ) was synthesized and their chemical structures characterized by ¹H NMR, ¹³C NMR, and mass spectroscopy. These compounds were evaluated as inhibitors for of type A and type B monoamine oxidase (MAO) enzymes. The most common inhibitors of MAO enzymes used to treat depression and anxiety such as selegiline and moclobemide drugs were used as reference agents. A result of biological evaluation of these compounds revealed compounds 4c , 4d , and 4? as potent and selective MAO A inhibitors. The most active compound 4? , which is 2,4‐dimethoxy at phenyl ring, showed strong inhibitory activity at MAO A (IC₅₀ of 0.0445 ± 0.0018μM). Furthermore, compounds 4c and 4d showed significant inhibition profile on MAO A with the IC₅₀ values 0.1423 ± 0.0051μM and 0.2148 ± 0.0067μM, respectively.     

Synthesis and biological evaluation of novel methylene‐bisthiazolidinone derivatives as potential nematicidal agents

In a one pot procedure, a series of novel methylene‐bis‐thiazolidinone derivatives 5 and 6 was prepared by condensation of 5‐(3‐formyl‐4‐methoxybenzyl)‐2‐methoxybenzaldehyde 3 with mercapto acids and primary aromatic amines 4 in presence of ZnCl₂ under both microwave irradiation and conventional heating conditions. High yields are achieved even on a gram scale, while reaction times are considerably shortened under microwave irradiation compared to conventional heating conditions. Characterization of new compounds has been done by means of IR, NMR, MS and elemental analysis. The nematicidal and antibacterial activity of the compounds has also been evaluated.     

Studies with enaminones: synthesis of new coumarin‐3‐yl azoles,coumarin‐3‐yl azines,coumarin‐3‐yl azoloazines,coumarin‐3‐yl pyrone and coumarin‐2‐yl benzo[b]Furans

3‐Acetylcoumarine was condensed with dimethylformamide dimethylacetal (DMFDMA) to yield the enaminone, which reacts readily with hydroxylamine and with hydrazines to yield coumarin‐3‐ylisoxazoles and coumarin‐3‐ylpyrazoles respectively. Reaction of the enaminone with benzamidine hydrochloride and 3‐amino‐1,2,4‐1H‐triazole affords the pyrimidine and triazolo[3,4‐b]pyrimidine. The enaminone reacts with hippuric acid and with the dithiocarboxylic acid to yield pyranones. The reaction of the enaminone with 3‐amino‐1H‐1,2,4‐triazole gives the triazolo[3,4‐b]pyrimidine. The enaminone underwent self dimerization on reflux in acetic acid ammonium acetate to yield the coumarinyl pyridines and reacted with ketone under the same conditions to yield the pyridine. The reaction of the enaminone with 1,4‐benzoquinone and 1,4‐naphthoquinone gives benzofuryl coumarine derivatives.     

Synthesis and biological evaluation of 5-methyl-4-phenyl thiazole derivatives as anticancer agents

Abstract

New N-(5-methyl-4-phenylthiazol-2-yl)-2-(substituted thio)acetamides were synthesized and studied for their anticancer activity. The title compounds were procured by reacting 2-chloro-N-(5-methyl-4-phenylthiazol-2-yl)acetamide with some mercapto derivatives. The structural elucidation of the compounds was performed by ¹H-NMR, ¹³C-NMR and LC-MS/MS spectral data and elemental analyses. The synthesized compounds were investigated for their antitumor activities against A549 human lung adenocarcinoma cells and NIH/3T3 mouse embryoblast cell line for determining their selective cytotoxicity. 2-[(1-methyl-1H-tetrazol-5-yl)thio]-N-(5-methyl-4-phenylthiazol-2-yl)acetamide (4c) showed high selectivity, and whose IC₅₀ value was determined as 23.30?±?0.35?µM and >1000?µM against A549 human lung adenocarcinoma cells and NIH/3T3 mouse embryoblast cell lines, respectively. 2-[(1-Methyl-1H-imidazol-2-yl)thio]-N-(5-methyl-4-phenyl thiazol-2-yl)acetamide (4a) and 2-[(1-Methyl-1H-tetrazol-5-yl)thio]-N-(5-methyl-4-phenyl thiazol-2-yl)acetamide (4c) exhibited the highest apoptosis percentage among those tested, but not as high as the standard, cisplatin.     

Synthesis and biological evaluation of novel imidazole-containing macrocycles

A new family of compounds made of a 5-aryl-1H-imidazole motif included in a macrocycle has been designed and synthesized. The synthesis of the imidazole core makes use of our previously developed method for the regioselective preparation of 1,2,5-trisubstituted imidazoles while the construction of the macrocycle is based on a three steps sequence: S_NAr, Suzuki coupling, and RCM reaction. Biological evaluation of synthesized imidazole-containing macrocycles revealed that they display actual binding activity toward A₃ adenosine (h) receptor, dopamine D₁ (h) receptor, chloride channel (GABA-gated), and choline transporter (h) CHT1.     

Synthesis and biological evaluation of novel derivatives of desloratadine

Series of novel derivatives of desloratadine designed as arginine vasopressin receptor antagonists were synthesized and structurally characterized by melting points,~1H NMR and HRMS.Their in vivo diuretic activities were evaluated on rats,and several target compounds showed promising diuretic results, especially compounds 8,18,27 and 31.Further in vitro bonding assay and cAMP assay showed that these compounds had a higher affinity to vasopressin V2 receptor than VI a receptor.Our studies indicated that desloratadine may be an active substructure for novel arginine vasopressin receptor antagonist development.     

Synthesis and biological evaluation of novel macrocyclic paclitaxel analogues

[reaction: see text] This work describes the synthesis of two novel macrocyclic taxoid constructs by ring-closing olefin metathesis (RCM) and their biological evaluation. Computational studies examine conformational profiles of 1 and 2 for their fit to the beta-tubulin binding site determined by electron crystallography. The results support the hypothesis that paclitaxel binds to microtubules in a "T" conformation.     

Synthesis and biological evaluation of novel steroid-linked nitrogen mustards

Two novel steroid-linked nitrogen mustard conjugates 1a and 1b were synthesized by using estrogenic acid 4 coupled with aniline mustard 8 and phenol mustard 13 in an esterification or amidation procedure. Preliminary cytotoxic screening on cancer cell lines in vitro showed that, the steroid-ester linked nitrogen mustard conjugate la exhibited obvious increasing of activities.     

Synthesis and biological activities of novel bis‐heterocyclic pyrrodiazole derivatives

Novel structures of bis‐heterocyclic pyrrodiazole derivatives containing pyrazole were designed and synthesized. The title compounds were characterized by ¹H NMR, IR, MS, and elemental analysis. Biological activities of three intermediate compounds and 25 pyrrodiazole derivatives were tested in vivo and in vitro. Some of the title compounds exhibited certain herbicidal activities against barnyardgrass and rape. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:21–27, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20369     

Synthesis and biological evaluation of two novel 2′-substituted tiazofurin analogues

Two novel tiazofurin analogues, 2-(2-benzamido-2-deoxy-β-d-ribofuranosyl)thiazole-4-carboxamide 4 and 2-(2-azido-2-deoxy-β-d-ribofuranosyl)thiazole-4-carboxamide 5, have been synthesized starting from d-glucose and evaluated for their in vitro cytotoxicity against several human leukaemia and solid tumour cell lines.     

Synthesis of novel azabicyclo derivatives containing a thiazole moiety and their biological activity against pine-wood nematodes

Abstract

To explore a new skeleton with nematicidal activity, a series of novel azabicyclo derivatives containing a thiazole moiety were designed, synthesized and evaluated for their nematicidal activities. The bioassay results against pine-wood nematodes (Bursaphelenchus xylophilus) showed that most of the title compounds displayed nematicidal activity at a concentration of 40?mg/L. Especially, the title compounds2-((8-methyl-8-azabicyclo[3.2.1]octan-3-yl)oxy)-4-(4-chlorophenyl)thiazole (7e), 2-((8-methyl-8-azabicyclo[3.2.1]octan-3-yl)thio)-4-phenylthiazole (10a) and 2-((8-methyl-8-azabicyclo [3.2.1]octan-3-yl)thio)-4-(4-chlorophenyl)thiazole (10e) exhibited more than 90% mortality against Bursaphelenchus xylophilus.     

Synthesis and biological evaluation of 9‐thia‐5,10‐dideazafolic acid

The folate analogue, 9‐thia‐5,10‐dideazafolic acid ( 3b ), was obtained in an efficient two‐step procedure in an overall yield of 60%. The previously unknown intermediate dimethyl‐thiocarbamic acid S‐(2‐amino‐3,4‐dihydo‐4‐oxo‐pyrido[2,3‐d]pyrimidin‐6‐yl) ester ( 5 ) was prepared via the condensation of 2,6‐diamino‐3H‐pyrimidin‐4‐one and S‐(2‐malonaldehyde)‐1,1,3,3‐tetramethylthiouronium bromide ( 4 ). Compound 5 , in a one pot procedure, was deprotected using sodium hydroxide and then coupled to diethyl N‐[(4‐chloromethyl)benzoyl]‐L‐glutamate, followed by saponification of the ethyl esters to give the 9‐thia‐5,10‐dideazafolic acid ( 3b ). Compound 3b was a potent inhibitor of human 5‐aminoimidazole‐4‐carboxamide ribonucleotide transformylase (K_i of 8 ± 5 μM) and showed no inhibition of human glycinamide ribonu‐cleotide transformylase at concentrations as high as 50 μM. Compound 3b was screened by the National Cancer Institute Developmental Therapeutics Program against 60 human tumors and was found to be active against a leukemia RPMI‐8226 cell line where the LC₅₀ was 1 μM.     

Synthesis and evaluation of novel ferrocene‐substituted triadimenol analogues

In search of potent 1H‐1,2,4‐triazole derivatives with improving antifungal activity, a class of novel ferrocene–triadimenol analogues was synthesized and their biological potential evaluated. Screening data revealed that these new derivatives did not have the antifungal activities of parent compounds, but showed unexpectedly promising plant growth regulatory activity. Copyright © 2006 John Wiley & Sons, Ltd.     

Synthesis and biological evaluation of novel fumagillin and ovalicin analogues

A promising approach among the numerous efforts to cure cancer is the interruption of the tumour-induced formation of new blood vessels (angiogenesis). By suppressing angiogenesis with drugs, the tumour can neither grow to a life threatening size, nor metastasize. The natural product fumagillin 1 and the structurally related ovalicin 2 are two of the most potent anti-angiogenic compounds. Here, we report the design and synthesis of novel fumagillin and ovalicin analogues lacking reactive epoxy functionalities, which were thought to be responsible for the severe toxic side-effects observed. We also report a new synthetic approach and the determination of the anti-angiogenic properties of these compounds in endothelial cells.