Synthesis and Microbial Studies of New Pyridine Derivatives-Ill

2-Amino substituted benzothiazole 4a--4I and p-acetamidobenzenesulfonyl chloride 2 were used to prepare 2-（p-aminophenylsulfonamido） substituted benzothiazole 6a--6I using mixture of pyridine and acetic anhydride which formed an electrophilic complex （N-acetyl pyridinium） to facilitate condensation to give desired product by removal of HC1. 2-{p-[（3-Carboxypyrid-2-y1）amino]phenylsulfonamido}benzothiazoles 8a--81 were synthesized from 2-chloropyridine-3-carboxylic acid 7 and 6a--6I in 2-ethoxy ethanol using Cu-powder and K2CO3. Acid chlorides 9a--91 were condensed with 2-hydroxyethyl piperazine 10 and 2,3-dichloropiperazine 11 for amide deriva- tives 2-（p-（（3-（4-（2-hydroxyethy1）piperazin-1-ylcarbonyl）pyrid-2-y1）amino）phenylsulfonamido）benzothiazoes 12a -121 and 2-{p-[3-（2,3-dichloropiperazin-l-ylcarbonyl）pyrid-2-ylamino]phenylsulfonamido}benzothiazoles 13a- 131 respectively. The structures of the new compounds have been established on the basis of their chemical analysis and spectral data （IR, 1↑H NMR and mass）. All the compounds have been screened for their antibacterial and antifungal activities.     

Synthesis,Characterization and Crystal Structure of Some Novel 1‐(3,5‐Dimethyl‐1H‐pyrazol‐1‐yl)‐3‐(substituted anilino)propan‐1‐ones

Michael addition of some substituted anilines to methyl acrylate in acidic medium afforded the methyl 3-(substituted anilino)propionates (1a—1i), which on treatment with hydrazine hydrate in methanol were converted into corresponding 3-(substituted anilino) propionohydrazides (2a—2i) in good yields. Microwave irradiation of the latter with pentane-2,4-dione afforded 1-(3,5-dimethyl-1H-pyrazol-1-yl)-3-(substituted anilino)propan-1-ones (3a—3i) under solventless conditions. The structures were confirmed by spectroscopic data, elemental analyses and in case of the 3h by single crystal X-ray diffraction data.     

Novel Approach for Rapid and Efficient Synthesis of 2‐(3‐(4‐Aryl)‐1‐isonicotinoyl‐4,5‐dihydro‐1H‐pyrazol‐4‐yl)‐3‐phenylthiazolidin‐4‐one Derivatives and Screened Their Antimicrobial Activity

A series of compounds, viz. 2‐(3‐(4‐aryl)‐1‐isonicotinoyl‐4,5‐dihydro‐1H‐pyrazol‐4‐yl)‐3‐phenylthiazolidin‐4‐one 4 ( a – n ), have been synthesized by reaction of 3 ( a – n ) with thioglycolic acid in the presence of zinc chloride. Compounds 3 ( a – n ) have been synthesized by amination of formylated pyrazoles 2 ( A – B ), which were synthesized by formylation of 1 ( A – B ) by Vilsmeier–Haack reagent (POCl₃/DMF). Compounds 1 ( A – B ) were synthesized by condensation of hydrazide and substituted acetophenones under conventional method and microwave irradiation method. These compounds were identified on the basis of melting point range, Rf values, infrared, ¹H NMR, and mass spectral analysis. These compounds were evaluated for their in vitro antimicrobial activity, and their minimum inhibitory concentration was determined. Among them, compound 4b and compound 4l possess appreciable antimicrobial and antifungal activities. Antibacterial activity results showed that compounds containing electron‐withdrawing groups were more active than compounds containing electron‐releasing groups.     

Synthesis and Cytotoxic Activity of Novel Pyrazoline Derivatives against Human Lung Tumor Cell Line (A549)

In the present investigation, a series of 5‐(‐4‐(substituted)phenyl)‐3‐(4‐hydroxy‐3‐methylphenyl)‐4,5‐dihydro‐1H‐1‐pyrazolyl‐2‐toluidino methane thione and 5‐(substituted)phenyl‐3‐(4‐hydroxy‐3‐methylphenyl)‐4,5‐dihydro‐1H‐1‐pyrazolyl‐2‐methoxy anilino methane thiones were synthesized and were examined against human lung tumor cell line (A549) in vitro using the MTT assay system. Among those tested, 5‐(4‐flurophenyl)‐3‐(4‐hydroxy‐3‐methylphenyl)‐4,5‐dihydro‐1H‐1‐pyrazolyl‐2‐toluidino methane thione & 5‐(4‐chlorophenyl)‐3‐(4‐hydroxy‐3‐methylphenyl)‐4,5‐dihydro‐1H‐1‐pyrazolyl‐2‐methoxy anilino methane thione showed more potent cytotoxicity against human lung tumor cell line (A549) than the other synthesized compounds.     

Synthesis and Characterization of 11‐Amino‐3‐methoxy‐8‐substituted‐12‐aryl‐8,9‐dihydro‐7H‐chromeno[2,3‐b]quinolin‐10(12H)‐one Derivatives

A series of 2‐amino‐7‐methoxy‐4‐aryl‐4H‐chromene‐3‐carbonitrile compounds 2 were obtained by condensation of 3‐methoxyphenol with β‐dicyanostyrenes 1 in absolute ethanol containing piperidine. The intermediate enamines 3 were prepared by compounds 2 with 5‐substituted‐1,3‐cyclohexanedione using p‐toluenesuflonic acid (TsOH) as catalyst. The title compounds 11‐amino‐3‐methoxy‐8‐substituted‐12‐aryl‐8,9‐dihydro‐7H‐chromeno[2,3‐b]quinolin‐10(12H)‐one 4 were synthesized by cyclization of the intermediate enamines 3 in THF with K₂CO₃ /Cu₂Cl₂ as catalyst. The structures of all compounds were characterized by elemental analysis, IR, MS, and ¹H NMR spectra. The crystal structure of compound 4i was determined by single‐crystal X‐ray diffraction analysis.     

Novel Copolymers of Styrene and Some Ring‐Substituted 2‐Cyano‐N,N‐Dimethyl‐3‐Phenyl‐2‐Propenamides

Electrophilic trisubstituted ethylene monomers, ring‐substituted 2‐cyano‐N,N‐dimethyl‐3‐phenyl‐2‐propenamides, RC₆H₄CH?C(CN)CON(CH₃)₂ (where R is 3‐benzyloxy, 4‐benzyloxy, 3‐ethoxy‐4‐methoxy, 3‐bromo‐4‐methoxy, 5‐bromo‐2‐methoxy, 2‐chloro‐6‐fluoro) were synthesized by potassium hydroxide catalyzed Knoevenagel condensation of ring‐substituted benzaldehydes and N,N‐dimethyl cyanoacetamide, and characterized by CHN elemental analysis, IR, ¹H‐ and ¹³C‐NMR. Novel copolymers of the ethylenes and styrene were prepared at equimolar monomer feed composition by solution copolymerization in the presence of a radical initiator, ABCN at 70°C. The composition of the copolymers was calculated from nitrogen analysis, and the structures were analyzed by IR, ¹H and ¹³C NMR, GPC, DSC, and TGA. High T_g of the copolymers in comparison with that of polystyrene indicates a substantial decrease in chain mobility of the copolymer due to the high dipolar character of the trisubstituted ethylene monomer unit. The gravimetric analysis indicated that the copolymers decompose in the 300–450°C range.     

Synthesis and Reactions of Halo-,Arylazo-substituted 3-(3-(1-naphthyl)acryloyl)tropolones.Formation of(Naphthalen-1-yl)vinyl)substituted Heterocycle-fused Troponoid Compounds

The starting substrate 3‐(3‐(1‐naphthyl)acryloyl)tropolone ( 3 ) was achieved by the aldol condensation reaction of 3‐acetyltropolone with 1‐naphthaldehyde. Compound 3 reacted with bromine to afford 7‐bromo‐3‐ (3‐(1‐naphthyl)acryloyl)tropolone ( 4 ), 5,7‐dibromo‐3‐(3‐(1‐naphthyl)acryloyl)tropolone (5) according to the molar ratio of the reactants. Iodination of 3 gave 7‐iodo‐3‐(3‐(1‐naphthyl)acryloyl)tropolone ( 6 ). Azo‐coupling reactions of 3 gave the 5‐arylazo‐3‐(3‐(1‐naphthyl)acryloyl)tropolones ( 7 – 8 ). Compounds 3 , 4 , 6 reacted respectively with hydroxyamine to give the corresponding 3‐[2‐(1‐naphthyl)vinyl]‐8H‐cyclohepta[d]isoxazol‐8‐ones ( 9 – 11 ). The reactions of 3 , 5 with phenylhydrazine and substituted phenylhydrazines gave 3‐[2‐(1‐naphthyl)vinyl]‐1‐phenylcyclohepta[c]pyrazol‐8(1H)‐ones ( 12 – 18 ).     

Synthesis and Transformation of Methyl 2‐(6‐Hydroxy‐2‐phenylpyrimidin‐4‐yl)acetate: Simple Preparation of Pyrimidines with Heterocyclic Substituents

A simple and efficient synthesis of four new substituted pyrimidines, compounds 9a – d , from the title compound 3 is described. Conversion of 3 to methyl (E)‐3‐(dimethylamino)‐2‐(6‐methoxy‐2‐phenylpyrimidin‐4‐yl)prop‐2‐enoate ( 4 ), followed by condensation with various dinucleophiles according to the ‘enaminone methodology’, afforded the target compounds 9 in medium‐to‐good yields.     

Synthese von neuen (Phenylalkyl)aminen zur Untersuchung von Struktur–Aktivitätsbeziehungen. Mitteilung 2

Synthesis of Novel (Phenylalkyl)amines for the Investigation of Structure–Activity Relationships. Part 2¹). 4‐Thio‐Substituted [2‐(2,5‐Dimethoxyphenyl)ethyl]amines (=2,5‐Dimethoxybenzeneethanamines) The 4‐substituted [2‐(2,5‐dimethoxyphenyl)ethyl]amines (=2,5‐dimethoxybenzeneethanamines) and its α‐methyl analogs are known to act as potent 5‐HT_2A/C ligands, which have, depending on their 4‐substituent, agonistic or antagonistic character. Generally, compounds with a small lipophilic substituent typically are agonists and those with a larger lipophilic substituent predominantly antagonists or at least partial agonists. Since little is known about the transition and more information is needed about the structural requirements of the 4‐substituent to control the functional activity, 12 novel 4‐thio‐substituted [2‐(2,5‐dimethoxyphenyl)ethyl]amines were synthesized and spectroscopically characterized. Thus 2,5‐dimethoxybenzenethiol ( 7 ) was converted to the thioether derivatives 8a – l with several alkyl, fluoroalkyl, alkenyl, and benzyl halides. Subsequent Vilsmeier‐formylation afforded the benzaldehydes 9a – l , condensation with MeNO₂ the nitroethenyl derivatives 10a – l , and reduction with AlH₃ the desired (2‐phenylethyl)amines 11a – l .     

7‐Halogenated 7‐Deazapurine 2′‐Deoxyribonucleosides Related to 2′‐Deoxyadenosine, 2′‐Deoxyxanthosine,and 2′‐Deoxyisoguanosine: Syntheses and Properties

A series of 7‐fluorinated 7‐deazapurine 2′‐deoxyribonucleosides related to 2′‐deoxyadenosine, 2′‐deoxyxanthosine, and 2′‐deoxyisoguanosine as well as intermediates 4b – 7b, 8, 9b, 10b , and 17b were synthesized. The 7‐fluoro substituent was introduced in 2,6‐dichloro‐7‐deaza‐9H‐purine ( 11a ) with Selectfluor (Scheme 1). Apart from 2,6‐dichloro‐7‐fluoro‐7‐deaza‐9H‐purine ( 11b ), the 7‐chloro compound 11c was formed as by‐product. The mixture 11b / 11c was used for the glycosylation reaction; the separation of the 7‐fluoro from the 7‐chloro compound was performed on the level of the unprotected nucleosides. Other halogen substituents were introduced with N‐halogenosuccinimides ( 11a → 11c – 11e ). Nucleobase‐anion glycosylation afforded the nucleoside intermediates 13a – 13e (Scheme 2). The 7‐fluoro‐ and the 7‐chloro‐7‐deaza‐2′‐deoxyxanthosines, 5b and 5c , respectively, were obtained from the corresponding MeO compounds 17b and 17c , or 18 (Scheme 6). The 2′‐deoxyisoguanosine derivative 4b was prepared from 2‐chloro‐7‐fluoro‐7‐deaza‐2′‐deoxyadenosine 6b via a photochemically induced nucleophilic displacement reaction (Scheme 5). The pK_a values of the halogenated nucleosides were determined (Table 3). ¹³C‐NMR Chemical‐shift dependencies of C(7), C(5), and C(8) were related to the electronegativity of the 7‐halogen substituents (Fig. 3). In aqueous solution, 7‐halogenated 2′‐deoxyribonucleosides show an approximately 70% S population (Fig. 2 and Table 1).     

One‐Pot,Step‐Wise,Alternative Syntheses of Quinoline‐Substituted Bis(Indolyl)Methanes Using a Green Approach

A green and highly efficient protocol for one‐pot, step‐wise, alternative syntheses of quinoline‐substituted bi(indolyl)methanes has been described by the condensation of N‐methyl or N‐ethyl quinolone‐4‐one‐3‐carbaldehydes 1a and b with indole 2a – f in water containing a catalytic amount of l ‐proline to afford the title compounds 5a – l in high yields and in shorter reaction times. This reaction involves easy workup without using column chromatography.     

Synthesis of 1‐[(1R)‐1‐(6‐fluoro‐1,3‐benzothiazol‐2‐yl)ethyl]‐3‐substituted phenyl ureas and their inhibition activity to acetylcholinesterase and butyrylcholinesterase

A series of novel 1‐[(1R)‐1‐(6‐fluoro‐1,3‐benzothiazol‐2‐yl)ethyl]‐3‐substituted phenyl ureas were synthesized by the condensation of (1R)‐1‐(6‐fluoro‐1,3‐benzothiazol‐2‐yl)ethanamine with substituted phenyl isocyanates under mild conditions. Their structures were confirmed ¹H, ¹³C, and ¹⁹F NMR spectra, and elemental analyses. The optical activities were confirmed by optical rotation measurements. The inhibition activity of 1‐[(1R)‐1‐(6‐fluoro‐1,3‐benzothiazol‐2‐yl)ethyl]‐3‐substituted phenyl ureas to acetylcholinesterase (ACHE) and butyrylcholinesterase (BCHE) was also tested. Preliminary bioassay indicated that the target ureas displayed excellent acetylcholinesterase and butyrylcholinesterase inhibition activity. J. Heterocyclic Chem., 2011.     

Three New Homoisoflavanones from the Ophiopogon japonicus Ker‐Gawler (Liliaceae)

Three new homoisoflavanones, 1 – 3 , together with a known one, 4 , were obtained from the AcOEt extract of the tuberous roots of Ophiopogon japonicus (Liliaceae). They were identified as (3R)‐2,3‐dihydro‐7‐hydroxy‐5‐methoxy‐3‐(4‐methoxybenzyl)‐6,8‐dimethyl‐4H‐chromen‐4‐one ( 1 ), (3R)‐3‐(1,3‐benzodioxol‐5‐ylmethyl)‐2,3‐dihydro‐7‐hydroxy‐5‐methoxy‐6,8‐dimethyl‐4H‐chromen‐4‐one ( 2 ), (3R)‐3‐(1,3‐benzodioxol‐5‐ylmethyl)‐2,3‐dihydro‐7‐hydroxy‐5‐methoxy‐6‐methyl‐4H‐chromen‐4‐one ( 3 ), and ophiopogonanone A ( 4 ). Their structures were determined on the basis of extensive NMR‐spectroscopic and mass‐spectrometric analyses. The three new compounds are rare homoisoflavanones which contain a MeO group at C(5). Compounds 1 and 2 showed weak cytotoxicity against the HepG2 (human hepatoma G2), KB (human oral epidermoid carcinoma), and MCF‐7 (human breast adenocarcinoma) cell lines in an MTT assay. Compound 3 exhibited weak cytotoxicity against HepG2 and MCF‐7, and moderate cytotoxicity against KB cell lines. Compound 4 showed moderate cytotoxicity against HepG2, KB, and MCF‐7 cell lines.     

Coumarinolignans from the Root of Formosan Antidesma pentandrum var. barbatum

Four new coumarinolignans, antidesmanin A (=7‐(1,1‐dimethylallyl)‐2,3‐dihydro‐3‐(4‐hydroxy‐3,5‐dimethoxyphenyl)‐10‐methoxy‐2‐methyl‐6H‐1,4,5‐trioxaphenanthren‐6‐one; 1 ), antidesmanin B (=3,7‐bis(1,1‐dimethylallyl)‐2,3‐dihydro‐2‐(4‐hydroxy‐3‐methoxyphenyl)‐10‐methoxy‐6H‐1,4,5‐trioxaphenanthren‐6‐one; 2 ), antidesmanin C (=2,7‐bis‐(1,1‐dimethylallyl)‐2,3‐dihydro‐3‐(4‐hydroxy‐3‐methoxyphenyl)‐10‐methoxy‐6H‐1,4,5‐trioxaphenanthren‐6‐one; 3 ) and antidesmanin D (=2‐(3,4‐dihydroxyphenyl)‐3,7‐bis(1,1‐dimethylallyl)‐2,3‐dihydroxy‐10‐methoxy‐6H‐1,4,5‐trioxaphenanthren‐6‐one or 3‐(3,4‐dihydroxyphenyl)‐2,7‐bis(1,1‐dimethylallyl)‐2,3‐dihydro‐10‐methoxy‐6H‐1,4,5‐trioxaphenanthren‐6‐one; 4 ) have been isolated from the root of the Formosan Antidesma pentandrum var. barbatum. The structures of these new compounds were elucidated by spectroscopic data. Compounds 1 – 3 exhibited marginal cytotoxicity against MCF‐7 (breast) and SF‐268 (CNS) cancer cell lines in vitro.     

Synthesis,crystal structures and anti‐inflammatory activity of fluorine‐substituted 1,4,5,6‐tetrahydrobenzo[h]quinazolin‐2‐amine derivatives

Two fluorine‐substituted 1,4,5,6‐tetrahydrobenzo[h]quinazolin‐2‐amine (BQA) derivatives, namely 2‐amino‐4‐(2‐fluorophenyl)‐9‐methoxy‐1,4,5,6‐tetrahydrobenzo[h]quinazolin‐3‐ium chloride, ( 8 ), and 2‐amino‐4‐(4‐fluorophenyl)‐9‐methoxy‐1,4,5,6‐tetrahydrobenzo[h]quinazolin‐3‐ium chloride, ( 9 ), both C₁₉H₁₉FN₃O⁺·Cl^?, were generated by Michael addition reactions between guanidine hydrochloride and the α,β‐unsaturated ketones (E)‐2‐(2‐fluorobenzylidene)‐7‐methoxy‐3,4‐dihydronaphthalen‐1(2H)‐one, C₁₈H₁₅FO₂, ( 6 ), and (E)‐2‐(4‐fluorobenzylidene)‐7‐methoxy‐3,4‐dihydronaphthalen‐1(2H)‐one, ( 7 ). Because both sides of α,β‐unsaturated ketones ( 6 ) or ( 7 ) can be attacked by guanidine, we obtained a pair of isomers in ( 8 ) and ( 9 ). Single‐crystal X‐ray diffraction indicates that each isomer has a chiral C atom and both ( 8 ) and ( 9 ) crystallize in the achiral space group P2₁/c. The chloride ion, as a hydrogen‐bond acceptor, plays an important role in the formation of multiple hydrogen bonds. Thus, adjacent molecules are connected through intermolecular hydrogen bonds to generate a banded structure. Furthermore, these bands are linked into an interesting 3D network via hydrogen bonds and π–π interactions. Fortunately, the solubilities of ( 8 ) and ( 9 ) were distinctly improved and can exceed 50 mg ml^?1 in water or PBS buffer system (pH 7.4) at room temperature. In addition, the results of an investigation of anti‐inflammatory activity show that ( 8 ) and ( 9 ), with o‐ and p‐fluoro substituents, respectively, display more potential for inhibitory effects on LPS‐induced NO secretion than starting ketones ( 6 ) and ( 7 ).     

Design,Synthesis, Characterization,and Antimicrobial Evaluation of Novel 2‐(3, 5‐di methoxy‐4‐((1‐aryl‐1H‐1, 2, 3‐triazole‐4‐yl) methoxy) phenyl) benzo[d]thiazoles

A series of 12 new 2‐(3, 5‐dimethoxy‐4‐((1‐Aryl‐4H‐1, 2, 3‐triazol‐4‐yl) methoxy) phenyl) benzo[d]thiazoles have been synthesized from the reaction of 4‐hydroxy‐3, 5‐dimethoxybenzaldehyde, o‐amino thiophenol, propargyl bromide, and different substituted aromatic azides using “click chemistry”. The structures of these compounds were established on the basis of Fourier Transform infrared, ¹H NMR, ¹³C–NMR, and mass spectral analysis. Compounds ( 6a–l ) were screened for in vitro antimicrobial activity.     

5(4H)‐Oxazolones as Novel Antitubercular Agents: Synthesis,Characterisation and Structure Activity Study

In search of novel anti tubercular agents, a series of twelve 4‐(substituted benzylidene)‐2‐p‐tolyloxazol‐5(4H)‐ones (5a – 5l) has been synthesized, characterised and subjected to evaluate their antitubercular activity for the first time against Mycobacterium tuberculosis H37Rv (ATCC 27294). The out‐put of these studies disclosed that all the synthesized target molecules of the series displayed good to moderate activity with MIC values ranging 2–32 μg/mL in comparison with the standard first line antitubercular drugs Rifampicin and Isoniazid. Compound 5e with three methoxy groups meta to each other, is the most distinctive compound identified amongst the series, because of its remarkable in vitro antitubercular activity and thus may act as a promising lead molecule for further explorations.     

Transformations of Methyl 2‐[(E)‐2‐(Dimethylamino)‐1‐(methoxycarbonyl)ethenyl]‐1‐methyl‐1H‐indole‐3‐carboxylate

A simple and efficient synthesis of novel 2‐heteroaryl‐substituted 1H‐indole‐2‐carboxylates and γ‐carbolines, compounds 1 – 3 , from methyl 2‐(2‐methoxy‐2‐oxoethyl)‐1‐methyl‐1H‐indole‐3‐carboxylate ( 4 ) by the enaminone methodology is presented.     

Synthesis and Characterization of New (Z)‐5‐((1H‐1,2,4‐Triazol‐1‐yl)methyl)‐3‐arylideneindolin‐2‐ones

Ten compounds of new (Z)‐5‐((1H‐1,24‐triazol‐1‐yl)methyl)‐3‐arylideneindolin‐2‐ones ( 5a – j ) have been synthesized by the Knoevenagel condensation of 5‐((1H‐1,2,4‐triazol‐1‐ylmethyl)indolin‐2‐one ( 3 ) with 4‐substituted aromatic aldehydes ( 4a – j ).     

Synthesis of Some Novel Phenyl Substituted Oxothiazolidin- 1’’,3’’,4’’-thiadiazolo-[3’,4’-b]thiazoline of 3β-Substituted Cholestane

Three title compounds 4a—4c have been synthesized by the cyclodehydration of 1’-benzylidine-4’-(3β-substituted-5α-cholestane-6-yl)thiosemicarbazones 2a—2c with thioglycolic acid followed by the treatment with cold conc. H2SO4 in dioxane. The compounds 2a—2c were prepared by condensation of 3β-substituted-5α-cholestan- 6-one-thiosemicarbazones 1a—1c with benzaldehyde. These thiosemicarbazones 1a—1c were obtained by the reaction of corresponding 3β-substituted-5α-cholestan-6-ones with thiosemicarbazide in the presence of few drops of conc. HCl in methanol. The structures of the products have been established on the basis of their elemental, analytical and spectral data.