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ArticleTitle Article Sub-Title Article CopyRight Journal Name Corresponding Author Springer Science+Business Media, LLC (This will be the copyright line in the final PDF) Medicinal Chemistry Research Family Name Particle Given Name Suffix Division Organization Address Email Author Family Name Particle Given Name Suffix Division Organization Address Email Author Family Name Particle Given Name Suffix Division Organization Address Email Received Schedule Abstract Revised Accepted 13 May 2011 A series of N-{5-[(2-chlorophenyl)methylene]-2-(4-hydroxyphenyl]-4-oxo(1,3-thiazolidin-3-yl)}{4-[2-(4methylphenyl)-4-oxo(3-hydroquinazolin-3-yl)]phenyl}carboxamides (6an) have been synthesized. All the synthesized compounds were screened for in vitro antibacterial and antifungal activities on Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Staphylococcus pyogenes, Candida albicans, Aspergillus niger, and Aspergillus clavatus. The structures of the compounds were elucidated by elemental analysis, IR, 1H NMR, 13C NMR, and Mass spectra. Quinazolinone - 4-Thiazolidinone - Antimicrobial activity 9 March 2011 Medicinal Chemistry Division, Department of Chemistry Bhavnagar University Bhavnagar, 364 002, India Prashant N. Shihora Medicinal Chemistry Division, Department of Chemistry Bhavnagar University Bhavnagar, 364 002, India Amit M. Medicinal Chemistry Division, Department of Chemistry Bhavnagar University Bhavnagar, 364 002, India dnisheeth@rediffmail.com Dodiya C. N. Desai A clubbed quinazolinone and 4-thiazolidinone as potential antimicrobial agents

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References Please update Ref. Desai and Dodiya (accepted for publication) with year of publication, volume number, and page numbers. References Narine et al. (1978), Kappe et al. (1994), Bawa et al. (2009) are cited in text but not provided in the reference list. Please provide references in the list or delete these citations. Reference Nanda et al. (2007) is given

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Med Chem Res DOI 10.1007/s00044-011-9674-5

MEDICINAL CHEMISTRY RESEARCH

ORIGINAL RESEARCH

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A clubbed quinazolinone and 4-thiazolidinone as potential antimicrobial agents

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Received: 9 March 2011 / Accepted: 13 May 2011 Springer Science+Business Media, LLC 2011

Keywords Quinazolinone 4-Thiazolidinone Antimicrobial activity

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Introduction

A1 A2 A3 A4

C. N. Desai (&) A. M. Dodiya P. N. Shihora Medicinal Chemistry Division, Department of Chemistry, Bhavnagar University, Bhavnagar 364 002, India e-mail: dnisheeth@rediffmail.com

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4(3H)-Quinazolinones and its derivatives constitute an important class of heterocyclic compounds. In view of wide range of bioactivities, this group of compounds dwell an important role in medicinal and pesticide chemistry. Having a broad spectrum of pharmacological activities, they act as an analgesic (Aly et al., 2010; Terashima et al., 1995), antimicrobial (Jatav et al., 2006; Dahiya and Kumar, 2008), antitumor (El-azab et al., 2010), anticancer (Giri et al., 2010), antiinammatory (Kumar and Rajput, 2009), anticonvulsant (Kashaw et al., 2010), antidepressant (Ergenc et al., 1991), hypolipidemic (Bekhit and Khalil, 1998), antiulcer (Hamel et al., 1996), or immunotropic

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Abstract A series of N-{5-[(2-chlorophenyl)methylene] -2-(4-hydroxyphenyl]-4-oxo(1,3-thiazolidin-3-yl)}{4-[2-(4 -methylphenyl)-4-oxo(3-hydroquinazolin-3-yl)]phenyl} carboxamides (6an) have been synthesized. All the synthesized compounds were screened for in vitro antibacterial and antifungal activities on Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Staphylococcus pyogenes, Candida albicans, Aspergillus niger, and Aspergillus clavatus. The structures of the compounds were elucidated by elemental analysis, IR, 1H NMR, 13C NMR, and Mass spectra.

activities (Gursoy and Karali, 1995). They also work as thymidyalate synthase (Baek et al., 1998), poly(ADPribose) polymerase (PARP) (Grifn et al., 1998) and protein tyrosine kinase (Sumegi et al., 2007) inhibitors. These compounds are also used as anti-HIV (Purohit et al., 2003) and antiviral agents (Liu et al., 1999) such as TMV, CMV inhibitors. With the inclining biological signicance, synthesis, and bioactivity of quinazoline derivatives have gained momentum amongst the biologist and chemist in recent past. Our group has reported that some of these compounds showed antimicrobial activity (Desai and Dodiya, accepted for publication). Nanda and his coworkers synthesized 3-(arylideneamino)-2-phenylquinazoline-4(3H)-ones, which were investigated for antibacterial activity against both gram-positive (Staphylococcus aureus 6571 and Bacillus subtilis) and gram-negative bacteria (Escherichia coli K12 and Shigella dysenteriae 6) using a turbidometric assay method. However, our group later found that the incorporation of 3-arylideneamino substituent enhanced the antibacterial activity of quinazolone system (Desai and Trivedi, 1993). For a long time small heterocycle scaffold containing nitrogen, sulfur, and oxygen have been under investigation due to their important medicinal properties. Among these types of molecules, 4-thiazolidinones have displayed various important biological activities (Capan et al., 1999; Vigorita et al., 2001; Kavitha et al., 2006; Ottana et al., 2005; Kucukguzel et al., 2006). Currently 4-thiazolidones are considered as a new class of antidiabetic (insulin-sensitising) drugs and potent aldose reductase inhibitors. In addition, they possess substantial potential for the treatment of diabetes complications like cataract, nephropathy, and neuropathy (Gerstein et al., 2006). Based on the results, we have designed and synthesized a series of N-{5[(2-chlorophenyl)methylene]-2-(4-hydroxyphenyl]-4-oxo

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C. N. Desai Amit M. Dodiya Prashant N. Shihora

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Results and discussion IR data

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(1,3-thiazolidin-3-yl)}{4-[2-(4-methylphenyl)-4-oxo(3-hydroquinazolin-3-l)]phenyl}carboxamides (6an). The condensation of 4-methylbenzoyl chloride and anthranilic acid in the presence of pyridine below 10C gives 2-(4-methylphenyl) benzo[d]1,3-oxazin-4-one (1), which when reacted with benzocain gave ethyl 4-[2-(4-methylphenyl)-4-oxo-3-hydroquinazolin-3-yl]benzoate (2) by the removal of water molecule. Compound (2) on reaction with hydrazine hydrate furnished N-amino{4-[2-(4-methylphenyl)-4-oxo-(3-hydroquinazolin-3-yl)]phenyl}carboxamide (3). Compound (3) on condensation with various aromatic aldehydes yielded schiff bases N-[(1Z)-1-aza-2-(4hydroxyphenyl)vinyl]{4-[2-(4-methylphenyl)-4-oxo-(3-hydroquinazolin-3-yl)]phenyl} (4). Then, further it produced N-[2-(4-hydroxyphenyl)-4-oxo-(1, 3-thiazolidin-3-yl)]{4-[2-(4-methylphenyl)-4-oxo-(3-hydroquinazolin-3-yl)] phenyl} carboxamide (5) by cycloaddition with mercaptoacetic acid in the presence of 1,4dioxane which on aldol condensation with different aryl aldehydes furnished N-{5-[(2-chlorophenyl)methylene]-2-(4-hydroxyphenyl]-4-oxo(1,3-thiazolidin-3-yl)}{4-[2-(4-methylphenyl) -4-oxo(3-hydroquinazolin-3-yl)]phenyl}-carboxamides (6an). The structures of compounds synthesized were assigned on the basis of elemental analysis, IR, 1H NMR, 13C NMR, and Mass spectra. These compounds were evaluated for their antimicrobial screening on different strains of bacteria and fungi Scheme 1.

range of 1520 cm-1 NO2 group symmetric stretching vibration while at 1345 cm-1 NO2 group asymmetric stretching vibration. The absorption peak at 860 cm-1 is due to the bending vibration of methylene group. The absorption peak at 774 cm-1 indicates that mono substituted benzene ring is present.
1

118 119 120 121 122 123 124

H NMR data

It has been observed from the chemical structure of compound 6g that different pairs of carbons, e.g., C-10 and C-15, C-11 and C-14, C-17 and C-21, C-18 and C-20, C-34 and C-38, C-35 and C-37 are attached to chemically equivalent protons, which appeared at d = 7.71, 7.28, 7.35, 7.76, 7.78, 6.63 ppm, respectively. The protons attached at C-13 position appeared as a singlet at d = 2.34 ppm due to the CH3 group. The proton of the hydroxy group appeared as singlet at 5.0 ppm. The proton attached to C-5 appeared as a multiplet at d = 7.63 ppm while the proton attached to C-6 appeared as a multiplet at d = 7.70 ppm. The proton attached to C-29 appeared as a multiplet at d = 7.66 ppm due to mutual coupling with protons attached to C-28 and C-30. The proton of the methylene group, which is attached to C-26 appeared as a singlet at d = 4.6 ppm. The proton of the secondary amine appeared as a singlet at d = 8.4 due to one side attachment with carbonyl group and another side with nitrogen atom. The proton of the C-30 appeared as a doublet at d = 8.14 ppm and C-32 appeared as a singlet at d = 8.31 ppm due to the inuence of nitro group on nearest position. The protons of the quinazolinone ring which are attached to C-7 and C-8 appeared as a doublet at d = 7.63 and 8.03 ppm, respectively.
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125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166

Author Proof

The IR spectrum of the title compound 6g (molecular formula C38H27N5O6S, m.w. 681.17) has given vibrations at 3082 and 3061 cm-1 over the ranges which showed multiple weak absorption peaks corresponding to QuH and ArH stretching vibration. The absorption peak at 3315 cm-1 is due to the stretching vibration of secondary amine which is part of amide linkage. The absorption peak at 3230 cm-1 is due to the stretching vibration of hydroxyl group. The absorption peak at 3050 cm-1 is due to the stretching vibration of methylene group, while the absorption at 2838 cm-1 is due to the stretching vibration of aromatic CH3 group, while the absorption at 1462 cm-1 is due to the bending vibration of aromatic CH3 group. The strong absorptions at 1719 and 1738 cm-1 are due to the C=O stretching vibration and amide group, while the moderate intensity absorption at 1653 cm-1 corresponds to a C=N stretching vibration, and C=C linkage stretching vibration appeared at 1608 cm-1. The presence of nitro group gives two vibrations, at the

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C NMR data

The chemical shifts of the nal compound 6g carbons vary from d = 164.8 to 24.3 ppm. The carbon nuclei under the inuence of a strong electronegative environment appeared downeld, e.g., the C-2, C-22, and C-23 carbonyl, which are directly linked to the ring nitrogen atom has a chemical shift value of d = 160.8, 164.8, and 164.4 ppm, respectively. The carbons C-1 which is attached on both sides to nitrogen atoms appeared at the same high value of d = 164.0 ppm. The chemical shift of the ring carbons at C-3, C-19, and C-24 are affected by the presence of the nearest carbonyl group, appeared at the same d = 120.8, 129.8, and 129.3 ppm, respectively. The C-31 appeared at d = 147.8 ppm due to the strong electron withdrawing inuence of nitro group while C-36 appeared at d = 147.8 ppm due to the strong electron withdrawing inuence of hydroxy group. The methyl group attached with the C-12 appeared at d = 139.8 ppm, while the carbon of the methyl group C-13 appeared at low value of

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Med Chem Res Scheme 1 Synthetic route of the title compounds. (i) NH2NH2H2O. (ii) Methanol, 6 h reux. (iii) Methanol, 5 h reux. (iv) HSCH2COOH. (v) 1,4dioxane, 6 h reux. (vi) 1,4dioxane, 8 h reux
O COOC2H5 O N N (2) R1 (3) (i) (ii) N NH2 O N R1 NH

(iii)

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O N N R1 (4) Where, R1 = C6H4-CH3 R2 = C6H4-OH R3 = Different substituents
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R2

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H O NH N R2

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O N O N (5) O (vi) (n-a)R3 H R1

NH N

R2 (iv) (v)

O N N R1

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O

(6a-n)

167 168 169 170 171 172 173 174 175 176 177 178 179 180 181 182 183 184

d = 24.3 ppm. The carbon of the methylene group C-26 appeared at d = 125.2 ppm. The carbon C-25 which is present in thiazolidine ring and which is attached on one side with nitrogen and on the other side with sulfur atom appeared at d = 63.4 ppm. The carbons of the 4-methyl phenyl ring which are attached to quinazolinone ring carbon at C-1 position having equivalent carbons like, C-10 and C-15 appeared at 126.0 ppm, while another equivalent carbon of this ring are C-11 and C-14 appeared at 129.1 ppm, respectively. The carbons of the phenyl ring, which is attached one side with amide group and another side to quinazolinone nucleus having equivalent carbons like, C-17 and C-21 appeared at 121.7 ppm, while C-18 and C-20 equivalent carbons appeared at 127.7 ppm. The 4-hydroxy phenyl ring with is attached with thiazoldine ring at C-25 position having equivalent carbons like C-34 and C-38 appeared at 129.1 ppm, while C-35 and C-37 appeared at 115.9 ppm. The carbons (C-27, C-28, C-29,

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O NH N R2 S R3

C-30, and C-32) of the 3-nirto phenyl ring which is attached with methylene linkage appeared from 120.0 to 136.1 ppm, respectively. The carbons (C-3, C-4, C-5, C-6, C-7, and C-8) of the quinazolinone ring appeared from 120.8 to 151.2 ppm, respectively. The carbon numbering is described in Fig. 1.

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Antimicrobial activity
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For antibacterial activity, compounds 6b, 6d, 6f, 6i, and 6j are considered to be good active against E.coli, while compounds 6m and 6n are considered as very good active against E.coli, while compounds 6c and 6g are considered as excellent active against E.coli. Compounds 6b, 6g, 6k, and 6m are considered as good active against P.aeruginosa, while compounds 6d and 6e are considered as very good active against P.aeruginosa. Compounds 6j and 6l are

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OH
37

O
18 38

36 35

O
4 5 3 2

17

19

22

NH N
25

33

34

N
1 9

16 21 15

20

S O
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6 7

32

10 11 12 13

NO2
31

CH3

28 30 29

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Fig. 1 Carbon numbering of the compound 6g

Antifungal activity 200 201 202 203 204 205 206 207 208 209 210 211 212 213 214 215 216 217 218 considered as good active against S.aureus, while compounds 6b, 6d, 6e, 6f, 6k, and 6m are considered as very good active against S.aureus, while compound 6g is considered as excellent active. Compounds 6a, 6c, 6d, 6h, 6l, and 6m are considered as good active against S.pyogenes, while compound 6f is considered as very good active against S.pyogenes. For the antifungal activity, compounds 6d, 6e, 6g, and 6n are considered as good active against C.albicans. Compounds 6b, 6c, 6g, 6i, and 6m are considered as good active against A.niger. Compounds 6d, 6f, 6i, and 6l are considered as good active against A.clavatus The antibacterial and antifungal activities have been enhanced due to the incorporation of 4-thiazolidine in quinazoline ring followed by the substitution at 5th position of 4-thiazolidine ring system due to the Knoevenagel reaction of active methylene group present at 5th. The discussion and comparison of antibacterial and antifungal activities have been compared with ampicillin and griseofulvin, respectively.

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primary screening were similarly diluted to obtain 100, 50, 25, 12.5 lg/ml concentrations. 10 lg/ml suspensions were further inoculated on appropriate media and growth was noted after 24 and 48 h. The lowest concentration, which showed no growth after spot subculture was considered as MIC for each drug. The highest dilution showing at least 99% inhibition is taken as (MIC). The test mixture should contain 108 cells/ml. The standard drug used in this study was ampicillin for evaluating antibacterial activity which showed (100, 100, 250, and 100 lg/ml) MIC against E. coli, P. aeruginosa, S. aureus, and S. pyogenes, respectively.

235 236 237 238 239 240 241 242 243 244 245 246

247 248 249 250 251 252 253 254 255 256 257 258 259 260 261 262 263 264 265 266

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Antibacterial activity

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While for the antifungal activity, same compounds were tested for antifungal activity in triplicate against Candida albicans, A. niger, and A. clavatus at various concentrations of 1000, 500, 200, and 100 lg/ml as shown in (Table 1). The results were recorded in the form of primary and secondary screening. The synthesized compounds were diluted at 1000 lg/ml concentration, as a stock solution. The synthesized compounds which were found to be active in this primary screening were further tested in a second set of dilution against all microorganisms. The lowest concentration, which showed no growth after spot subculture was considered as (MIC) for each drug. The highest dilution showing at least 99% inhibition is taken as MIC. The test mixture should contain 108 spores/ml MIC. griseofulvin was used as a standard drug for antifungal activity, which showed (500, 100, and 100 lg/ml) MIC against C. albicans, A. niger, and A. clavatus, respectively. The results of antimicrobial evaluation of derivatives (6an) are collected in (Table 1).

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Statistical analysis The standard deviation value is expressed in terms of SD. On the basis of the calculated value by using ANOVA method, it has been observed that the differences below 0.0001 level (P B 0.0001) were considered as statistically signicant.

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For the antibacterial activity, the newly synthesized compounds were screened for their antibacterial activity against gram positive bacteria S. aureus (MTCC-96) and Streptococcus pyogenes (MTCC-442) and gram negative E. coli (MTCC-443) and Pseudomonas aeruginosa (MTCC1688)]. Antibacterial activity was carried out by serial broth dilution method (Ghalem and Mohamed, 2009; Desai and Trivedi, 1993; Al-Bayati and Al-Mola, 2008). The standard strains used for the antimicrobial activity was procured from Institute of Microbial Technology, Chandigarh. The compounds (6an) were screened for their antibacterial activity in triplicate against E. coli, S. aureus, P. aeruginosa, and S. pyogenes at different concentrations of 1000, 500, 200, 100, 50, 25, 12.5 lg/ml as shown in (Table 1). The drugs which were found to be active in

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Materials and methods All the required chemicals were purchased from E. Merck. 2-Chloro-6-methylquinoline-3-carbaldehyde was synthesized (Narine et al., 1978) and modied (Kappe et al., 1994; Bawa et al., 2009). IR spectra were recorded on Perkin Elmer FTIR spectrophotometer. 1H NMR and 13C

273 274 275 276 277 278

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Med Chem Res Table 1 Results of antibacterial and antifungal screening of the compounds (6an) Sr. no. R3 Minimum inhibitory concentration (MIC) in ug/ml SD E. coli MTCC 443 6a 6b 6c 6d 6e 6f 6g 6h H 3,4,5-(OCH3)3 P. aeruginosa S. aureus MTCC 1688 MTCC 96 S. pyogenes MTCC 442 Minimum inhibitory concentration (MIC) ug/ml SD C. albicans MTCC 227 500 2.51* A. niger MTCC 282 1000 4.50* 100 3.51* 100 4.35* 1000 3.60* 500 4.50* 1000 4.58* A. clavatus MTCC 1323 1000 3.05* 1000 4* 500 3.78* 100 3.05*

200 4.50* 500 3.78* 100 4.72* 100 3.05*

500 4.04* 100 4.04*

100 3.05* 200 2.51* 1000 4.04* 1000 4.04* 100 4.50* 1000 4* 100 3.78* 100 4* 100 4.58* 100 3.05* 250 1* 100 2.51* 50 3.51* 500 1* 500 3* 100 4.04* 100 2.30* 50 3.51* 1000 4.50*

4F 4OH 3NO2 2Cl 4OCH3 2OCH3 2OH5Br 2,6-(Cl)2 4Cl

500 3.78*

50 4*

100 4.04* 500 3.46* 25 4.93* 100 4.58* 200 4* 500 3.60* 100 3.78* 500 4.04* 500 3.21* 100 3.05* 500 4.58* 500 3.51* 50 4.04* 200 2* 50 3* 100 2.0* 100 3.21* 100 1.0*

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100 4.04* 1000 3.05* 100 3.51* 500 4.16* 100 3.60* 100 1* 1000 3.51* 1000 4* 1000 3*

500 4.04* 100 1.32* 1000 3.21* 250 3.21* 500 4.16* 100 3.51* 500 2.08* 250 3.05* 100 3.60* 100 3.53* 100 2* 500 1.56* 500 3.45* 250 1.52* 100 2.08*

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6i 6j 6k 6l 6m 6n

500 4.04* 1000 3.51* 500 3.46* 500 3.78* 500 3.05*

2OH4OCH3 100 3.21* 200 3.51*

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Ampicillin Griseofulvin

SD standard deviation, * P B 0.0001

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Experimental

Synthesis of 1 and 2

2-(4-methylphenyl)benzo[d]1,3-oxazin-4-one 1 and 2-(4methylphenyl)-3-(4-propanoylphenyl)-3-hydroquinazolin4-one 2 have been synthesized as described previously (Pandey et al., 2005).

The intermediate compound 3 has been achieved by a mixture of 2-(4-methylphenyl)-3-(4-propanoylphenyl)-3hydroquinazolin-4-one 2 (0.01 mol) and excess of hydrazine hydrate (99%, 0.015 mol) in methanol (40 ml) was

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Preparation of N-amino{4-[2-(4-methylphenyl)-4oxo(3-hydroquinazolin-3-yl)]phenyl}carboxamide (3)

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NMR spectra were recorded on Bruker DPX-40C instrument at 400 MHz. Chemical shifts were reported in ppm in reference to the residual solvent signal. Mass spectra were recorded on JEOL SX-102. Elemental analysis was performed by Perkin-Elmer 2400-CHN analyzer. Melting points were recorded on Gallenkamp apparatus and were left uncorrected. Aluminum coated TLC plates 60 F245 (E. Merck) were used for monitoring of reaction and purity of compounds. In the conventional method, compounds were synthesized by using Random synthesizer. Bookie Rotavapour was used for distillation.

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added to a round bottom ask. The contents were reuxed for 6 h. After the reaction was completed, the reaction mixture was poured into crushed ice to afford dark brown precipitate. This was collected by ltration and washed with cold water. The resulting solid was recrystallized from ethanol (99%). M.p.: 182C, Yield 75%; IR (KBr): 3426 cm-1 (NH stretching, primary amine), 3311 cm-1 (NH stretching, secondary amine), 3084, 3062 cm-1 (QuH and ArH stretching, aromatic ring), 2837 cm-1 (CH stretching, CH3 group), 1713 cm-1 (C=O stretching, amide group), 1648, 1605 cm-1 (C=N, C=C stretching, aromatic ring), 1341 cm-1 (CN stretching, quinazoline ring), 771 cm-1 (para-substitution of aromatic ring); 1H NMR (CDCl3): 7.07.9 (m, 12H, ArH), 8.0 (s, 1H, CONH), 2.3 (s, 3H, ArCH3), 2.0(s, 2H, NNH2); 13C NMR: 21.3, 120.8, 124.5, 125.6, 126.6, 126.7, 127.3, 127.6, 129.1, 129.6, 130.3, 133.4, 136.1, 139.8, 148.7, 156.2, 160.6, 167.2. GCMS: m/z: 370.14 (M?). Anal. calcd. for C22H18N4O2: C, 71.33; H, 4.89; N, 15.12. Found: C, 71.52; H, 4.60; N, 15.26. Preparation of N-[(1Z)-1-aza-2-(4hydroxyphenyl)vinyl]{4-[2-(4-methylphenyl)-4-oxo(3hydroquinazolin-3-yl)]phenyl}carboxamide (4) The intermediate compound 4 has been achieved by a mixture of N-amino{4-[2-(4-methylphenyl)-4-oxo(3-hydroquinazolin-3-yl)]phenyl}carboxamides 3 (0.01 mol)

N(CH3)2 25 4.93* 200 4.04* 2OHnaphthyl 100 4.04* 50 4.58

1000 3.60* 100 4.04* 500 4.04* 1000 4.16* 100 3* 500 4.04* 500 3.05* 100 2.51* 1000 2* 1000 3* 100 1.15*

302 303 304 305 306 307 308 309 310 311 312 313 314 315 316 317 318 319 320 321 322 323 324 325 326 327 328

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The synthesis of intermediate compound 5 has been achieved by a mixture of N-[(1Z)-1-aza-2-(4-hydroxyphenyl)vinyl]{4-[2-(4-methylphenyl)-4-oxo(3-hydroquinazolin-3-yl)]phenyl}carboxamides 4 (0.01 mol) and mercaptoacetic acid (0.011 mol) in 1:4 dioxane (40 ml) was reuxed for 6 h. After the reaction completed, the solution was poured into ice-cold aqueous solution of sodium bicarbonate to remove unreacted mercaptoacetic acid. The yellow to brown precipitate was ltered, and then washed with cold water. The resulting solid was recrystallized from ethanol (99%). M.p.: 242C, Yield 68%; IR (KBr): 3315 cm-1 (NH stretching, secondary amine), 3230 cm-1 (OH stretching, OH group), 3081, 3065 cm-1 (QuH and ArH stretching, aromatic ring), 2835 cm-1 (CH stretching, CH3 group), 1738, 1717 cm-1 (C=O stretching, amide group), 1648, 1605 cm-1 (C=N, C=C stretching, aromatic ring), 1341 cm-1 (CN stretching, quinazoline ring), 776 cm-1 (ortho substitution of aromatic ring); 1H NMR (CDCl3): d 6.67.9 (m, 16H, ArH), 8.0(s, 1H, CONH), 5.9 (s, 1H, NCHS), 4.9 (s, 1H, ArOH), 3.3 (s, 2H, COCHS). 13 C NMR (CDCl3): d 21.3, 32.4, 62.2, 115.7, 120.8, 124.5, 125.6, 126.6, 126.7, 127.0, 127.3, 127.6, 129.1, 129.6, 130.3, 133.4, 136.1, 139.8, 148.7, 156.2, 156.5, 160.6, 163.7, 164.9; GCMS: m/z: 648.14 (M?). Anal. calcd. for C31H24N4O4S: C, 67.86; H, 4.40; N, 10.21. Found: C, 67.27; H, 4.86; N, 10.52.

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Preparation of N-[2-(4-hydroxyphenyl)-4-oxo(1,3thiazolidin-3-yl)]{4-[2-(4-methylphenyl)-4-oxo(3hydroquinazolin-3-yl)]-phenyl}carboxamide (5)

M.p.: 132C, Yield 68%; IR (KBr): 3310 cm-1 (NH stretching, secondary amine), 3230 cm-1 (OH stretching, OH group), 3120 cm-1 (CH stretching, aromatic ring), 3052 (=CH stretching), 2900 cm-1 (CH stretching, CH3 group), 1710, 1725 cm-1 (C=O stretching, amide group), 1630, 1610 cm-1 (C=N, C=C stretching, aromatic ring), 1345 cm-1 (CN stretching, quinazoline ring), 920 cm-1 (ortho-substitution of aromatic ring), 864 (=CH bending); 1 H NMR (CDCl3): d 6.07.9 (m, 21H, ArH), 8.3 (s, 1H, CONH), 4.7 (s, 1H, C=CHAr), 5.9 (s, 1H, NCHS), 5.0 (s, 1H, ArOH); 13C NMR (CDCl3): d 24.3, 63.4, 115.9, 120.8, 121.7, 122.4, 125.2, 125.6, 126.0, 126.4, 127.4, 127.7, 128.0, 128.7, 128.8, 129.1, 129.3, 129.8, 133.5, 134.5, 135.2, 136.1, 139.8, 151.2, 156.9, 160.8, 164.1, 164.3, 164.5; GCMS: m/z: 613.18 (M?). Anal. calcd. for C38H28N4O4S: C-71.68%, H-4.43%, N-8.80%. Found: C-71.74%, H-4.49%, N-8.85%. Physical constants and characterization of N-{5-[(3,4,5trimethoxyphenyl)methylene]-2-(4-hydroxyphenyl)-4oxo- (1,3-thiazolidin-3-yl)} {4-[2-(4-methylphenyl)-4oxo(3-hydroquinazolin-3-yl)]phenyl}carboxamide (6b) M.p.: 125C, Yield 71%; IR (KBr): 3311 cm-1 (NH stretching, secondary amine), 3231 cm-1 (OH stretching, OH group), 3122 cm-1 (CH stretching, aromatic ring), 3061 (=CH stretching), 2902 cm-1 (CH stretching, CH3 group), 1713, 1724 cm-1 (C=O stretching, amide group), 1632, 1611 cm-1 (C=N, C=C stretching, aromatic ring), 1346 cm-1 (CN stretching, quinazoline ring), 1255 cm-1 (CO stretching, ether group), 924 cm-1 (ortho-substitution of aromatic ring), 859 (=CH bending); 1H NMR (CDCl3): d 6.17.9 (m, 18H, ArH), 8.4 (s, 1H, CONH),

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and 4-hydroxybenzaldehyde (0.01 mol) (over a period of 10 min) in methanol (30 ml) was reuxed for 5 h. After the reaction was completed, the light brown schiff base comes out. This was collected by ltration. The resulting solid was recrystallized from methanol. M.p.: 222C, Yield 78%; IR (KBr): 3312 cm-1 (NH stretching, secondary amine), 3233 cm-1 (OH stretching, OH group), 3081, 3065 cm-1 (QuH and ArH stretching, aromatic ring), 2832 cm-1 (CH stretching, CH3 group), 1714 cm-1 (C=O stretching, amide group), 1644, 1603 cm-1 (C=N, C=C stretching, aromatic ring), 1344 cm-1 (CN stretching, quinazoline ring), 774 cm-1 (ortho substitution of aromatic ring); 1H NMR (CDCl3): d 6.87.9 (m, 16H, ArH), 8.1(s, 1H, CONH), 8.1 (s, 1H, N=CH), 5.0 (s, 1H, ArOH); 13C NMR: 21.3, 116.0, 120.8, 124.5, 125.6, 126.3, 126.6, 126.7, 127.3, 128.4, 129.1, 129.6, 130.3, 130.6, 133.4, 136.1, 139.8, 146.8, 148.7, 156.2, 160.8, 163.2; GCMS: m/z: 474.17 (M?). Anal. calcd. for C29H22N4O3:C, 76.09; H, 4.89; N, 8.87. Found: C, 76.29; H, 4.60; N, 8.60.

General preparation of N-{5-[(aryl)methylene]-2-(4hydroxyphenyl)-4-oxo(1,3-thiazolidin-3-yl)}{4-[2-(4methylphenyl)-4-oxo(3-hydroquinazolin-3yl)]phenyl}carboxamides (6an) A mixture of a sodium methoxide solution of N-[2-(4hydroxyphenyl)-4-oxo(1,3-thiazolidin-3-yl)] {4-[2-(4-methylphenyl)-4-oxo(3-hydroquinazolin-3-yl)]phenyl}carboxamide 5 (0.01 mol) and benzaldehyde (0.01 mol) in 1:4 dioxane (40 ml) was reuxed for 8 h. After the reaction was completed, the reaction mixture was pour into crushed ice to afford brown precipitate. This was collected by ltration, and then washed with cold water. The resulting solid was recrystallized from ethanol (99%). Physical constants and characterization of N-{5[(phenyl)methylene]-2-(4-hydroxyphenyl)-4-oxo(1,3thiazolidin-3-yl)}{4-[2-(4-methylphenyl)-4-oxo(3hydroquinazolin-3-yl)] phenyl}carboxamide (6a)

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4.9 (s, 1H, C = CHAr), 5.9 (s, 1H, NCHS), 5.1 (s, 1H, ArOH), 3.7 (s, 9H, ArOCH3); 13C NMR (CDCl3): d 24.3, 56.1, 56.4, 63.4, 103.8, 115.9, 120.8, 121.7, 122.4, 125.2, 125.6, 126.0, 127.4, 127.7, 128.8, 129.1, 129.3, 129.5, 129.8, 133..5, 134.5, 136.1, 138.4, 139.8, 150.7, 151.2, 156.9, 160.8, 164.2, 164.5, 164.6; GCMS: m/z: 726.21 (M?). Anal. calcd. for C41H34N4O7S: C-67.75%, H-4.72%, N-7.71%. Found: C-67.81%, H-4.76%, N-7. 75%.

5.0 (s, 1H, ArOH), 5.1 (s, 1H, ArOH); 13C NMR (CDCl3): d 24.3, 63.4, 115.9, 117.7, 117.8, 120.8, 121.7, 122.3, 122.4, 123.6, 125.2, 125.6, 126.0, 126.8, 127.4, 127.7, 128.5, 128.8, 129.1, 129.3, 129.8, 130.1, 131.9, 133.5, 134.5, 136.1, 139.8, 151.2, 155.8, 156.9, 160.6, 164.2, 164.3, 164.6; GCMS: m/z: 702.19 (M?). Anal. calcd. for C42H30N4O5S: C-71.78%, H-4.30%, N-7.97%. Found: C-71.82%, H-4.34%, N-7.99%. Physical constants and characterization of N-{5-[(4uorophenyl)methylene]-2-(4-hydroxyphenyl)-4oxo(1,3-thiazolidin-3-yl)} {4-[2-(4-methylphenyl)-4oxo(3-hydroquinazolin-3-yl)]phenyl}carboxamide (6e) M.p.: 175C, Yield 74%; IR (KBr): 3313 cm-1 (NH stretching, secondary amine), 3231 cm-1 (OH stretching, OH group), 3123 cm-1 (CH stretching, aromatic ring), 3045 (=CH stretching), 2906 cm-1 (CH stretching, CH3 group), 1711, 1723 cm-1 (C=O stretching, amide group), 1634, 1616 cm-1 (C=N, C=C stretching, aromatic ring), 1344 cm-1 (CN stretching, quinazoline ring), 1250 cm-1 (CF stretching), 924 cm-1 (ortho substitution of aromatic ring), 860 (=CH bending); 1H NMR (CDCl3): d 6.17.9 (m, 20H, ArH), 8.3 (s, 1H, CONH), 4.9 (s, 1H, C = CH Ar), 5.9 (s, 1H, NCHS), 5.1 (s, 1H, ArOH); 13C NMR (CDCl3): d 24.3, 63.4, 115.4, 115.9, 120.8, 121.7, 122.4, 125.2, 125.6, 126.0, 127.4, 127.7, 128.0, 128.8, 129.1, 129.3, 129.8, 130.8, 133.5, 134.5, 136.1, 139.8, 151.2, 156.9, 162.1, 160.5, 164.0, 164.2, 164.8; GCMS: m/z: 654.17 (M?). Anal. calcd. for C38H27FN4O4S: C-69.71%, H-4.16%, N-8.56%. Found: C-69.76%, H-4.21%, N-8. 60%. Physical constants and characterization of N-{5-[(4hydroxyphenyl)methylene]-2-(4-hydroxyphenyl)-4oxo(1,3-thiazolidin-3-yl)} {4-[2-(4-methylphenyl)-4oxo(3-hydroquinazolin-3-yl)]phenyl}carboxamide (6f) M.p.: 255C, Yield 65%; IR (KBr): 3317 cm-1 (NH stretching, secondary amine), 3235 cm-1 (OH stretching, OH group), 3120 cm-1 (CH stretching, aromatic ring), 3055 (=CH stretching), 2900 cm-1 (CH stretching, CH3 group), 1715, 1727 cm-1 (C=O stretching, amide group), 1634, 1613 cm-1 (C=N, C=C stretching, aromatic ring), 1346 cm-1 (CN stretching, quinazoline ring), 863 (=CH bending), 927 cm-1 (ortho substitution of aromatic ring); 1 H NMR (CDCl3): d 6.57.9 (m, 20H, ArH), 8.1 (s, 1H, CONH), 4.8 (s, 1H, C = CHAr), 5.8 (s, 1H, NCH S), 5.1 (s, 1H, ArOH), 5.0 (s, 1H, ArOH); 13C NMR (CDCl3): d 24.3, 63.4, 115.8, 115.9, 120.8, 121.7, 122.4, 125.2, 125.6, 126.0, 127.4, 127.7, 127.8, 128.8, 129.1, 129.3, 129.8, 133.5, 134.5, 136.1, 139.8, 151.2, 156.9,

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Physical constants and characterization of N-{5-[(1hydroxy(2-naphthyl))methylene)]-2-(4hydroxyphenyl)-4-oxo(1,3-thiazolidin-3-yl)}{4-[2-(4methylphenyl)-4-oxo(3-hydroquinazolin-3-yl)]phenyl}carboxamide (6d) M.p.: 160C, Yield 55%; IR (KBr): 3313 cm-1 (NH stretching, secondary amine), 3233 cm-1 (OH stretching, OH group), 3124 (CH stretching, aromatic ring), 3051 (=CH stretching), 2904 cm-1 (CH stretching, CH3 group), 1713, 1725 cm-1 (C=O stretching, amide group), 1636, 1615 cm-1 (C=N, C=C stretching, aromatic ring), 1343 cm-1 (CN stretching, quinazoline ring), 920 cm-1 (ortho substitution of aromatic ring), 863 (=CH bending); 1 H NMR (CDCl3): d 6.67.9 (m, 20H, ArH), 8.5 (s, 1H, CONH), 4.7 (s, 1H, C=CHAr), 5.9 (s, 1H, NCHS),

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M.p.: 100C, Yield 70%; IR (KBr): 3314 cm-1 (NH stretching, secondary amine), 3232 cm-1 (OH stretching, OH group), 3124 cm-1 (CH stretching, aromatic ring), 3056 (=CH stretching), 2903 cm-1 (CH stretching, CH3 group), 1713 cm-1, 1723 cm-1 (C=O stretching, amide group), 1632, 1612 cm-1 (C=N, C=C stretching, aromatic ring), 1347 cm-1 (CN stretching, quinazoline ring), 926 cm-1 (ortho-substitution of aromatic ring), 857 (=CH bending); 1H-NMR (CDCl3): d 6.67.9 (m, 20H, ArH), 8.2 (s, 1H, CONH), 4.6 (s, 1H, C=CHAr), 5.9 (s, 1H, NCHS), 5.0 (s, 1H, ArOH), 2.8 (s, 6H, ArN(CH3)2); 13 C NMR (CDCl3): d 24.3, 40.2, 63.4, 114.2, 115.9, 120.8, 121.7, 122.4, 124.7, 125.2, 125.6, 126.0, 127.3, 127.4, 127.7, 128.8, 129.1, 129.3, 129.8, 133.5, 134.5, 136.1, 139.8, 148.8, 151.2, 156.9, 160.7, 164.2, 164.4, 164.7; GCMS: m/z: 679.23 (M?). Anal. calcd. for C40H53N5O4 S: C-70.67%, H-4.89%, N-10.30%. Found: C-70.72%, H-4.93%, N-10.35%.

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Physical constants and characterization of N-{5-[(4(dimethylamino)phenyl)methylene]-2-(4hydroxyphenyl)-4-oxo(1,3-thiazolidin-3-yl)}{4-[2-(4methylphenyl)-4-oxo(3-hydroquinazolin-3yl)]phenyl}carboxamide (6c)

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157.7, 164.0, 160.8, 164.4, 164.8; GCMS: m/z: 652.18 (M?). Anal. calcd. for C38H28N4O5S: C-69.92%, H-4.32%, N-8.58%. Found: C-69.96%, H-4.38%, N-8.64%.

C38H27ClN4O4S: C-68.00%, H-4.05%, N-8.35%. Found: C-68.05%, H-4.11%, N-8.39%.

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M.p.: 111C, Yield 59%; IR (KBr): 3315 cm-1 (NH stretching, secondary amine), 3230 cm-1 (OH stretching, OH group), 3083, 3061 cm-1 (QuH and ArH stretching, aromatic ring), 3050 (=CH stretching), 2838 cm-1 (CH stretching, CH3 group), 1738, 1719 cm-1 (C=O stretching, amide group), 1653, 1608 cm-1 (C=N, C=C stretching, aromatic ring), 1520 cm-1 (NO2 group asymmetric stretching), 1345 cm-1 (CN stretching, quinazoline ring), 1345 (NO2 group symmetric stretching), 860 (=CH bending), 774 cm-1 (ortho substitution of aromatic ring); 1H NMR (CDCl3): d 6.07.9 (m, 20H, ArH), 8.4 (s, 1H, CONH), 4.6 (s, 1H, C=CHAr), 5.9 (s, 1H, N CHS), 5.0 (s, 1H, ArOH); 13C NMR (CDCl3): d 24.3, 63.4, 115.9, 120.0, 120.8, 123.1, 121.7, 122.4, 125.2, 125.6, 126.0, 127.4, 127.7, 128.8, 129.1, 129.3, 129.6, 129.8, 132.5, 133.5, 134.5, 136.1, 139.8, 147.8, 151.2, 156.9, 160.8, 164.1, 164.3, 164.8; GCMS: m/z: 681.17 (M?). Anal. calcd. for C38H27N5O6S: C-66.95%, H-3.99%, N-10.27%. Found: C-66.99%, H-3.97%, N-10.32%.

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M.p.: 300C, Yield 72%; IR (KBr): 3316 cm-1 (NH stretching, secondary amine), 3238 cm-1 (OH stretching, OH group), 3120 cm-1 (CH stretching, aromatic ring), 3048 (=CH stretching), 2903 cm-1 (CH stretching, CH3 group), 1715, 1728 cm-1 (C=O stretching, amide group), 1635, 1615 cm-1 (C=N, C=C stretching, aromatic ring), 1349 cm-1 (CN stretching, quinazoline ring), 862 (=CH bending), 926 cm-1 (ortho substitution of aromatic ring); 1 H NMR (CDCl3): d 6.17.9 (m, 18H, ArH), 8.4 (s, 1H, CONH), 4.7 (s, 1H, C=CHAr), 5.8 (s, 1H, NCHS), 5.0 (s, 1H, ArOH), 3.6 (s, 3H, ArOCH3); 13C NMR (CDCl3): d 24.3, 55.8, 63.4, 114.2, 115.9, 120.8, 121.7, 122.4, 125.2, 125.6, 126.0, 127.4, 127.5, 127.7, 128.8, 129.1, 129.3, 129.8, 133.5, 134.5, 136.1, 139.8, 151.2, 156.9, 159.8, 160.3, 164.0, 164.1, 164.5; GCMS: m/ z: 666.19 (M?). Anal. calcd. for C39H30N4O5S: C-70.25%, H-4.54%, N-8.40%. Found: C-70.30%, H-4.59%, N-8. 46%.

Physical constants and characterization of N-{5-[(3nitrophenyl)methylene]-2-(4-hydroxyphenyl)-4oxo(1,3-thiazolidin-3-yl)} {4-[2-(4-methylphenyl)-4oxo(3-hydroquinazolin-3-yl)]phenyl}carboxamide (6g)

Physical constants and characterization of N-{5-[(4methoxyphenyl)methylene]-2-(4-hydroxyphenyl)-4oxo(1,3-thiazolidin-3-yl)}{4-[2-(4-methylphenyl)-4oxo(3-hydroquinazolin-3-yl)]phenyl}carboxamide (6i)

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Physical constants and characterization of N-{5-[(2chlorophenyl)methylene]-2-(4-hydroxyphenyl)-4oxo(1,3-thiazolidin-3-yl)} {4-[2-(4-methylphenyl)-4oxo(3-hydroquinazolin-3-yl)]phenyl}carboxamide (6h)

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Physical constants and characterization of N-{5-[(4methoxy-2-hydroxyphenyl)methylene]-2-(4hydroxyphenyl)-4-oxo(1,3-thiazolidin-3-yl)}{4-[2-(4methylphenyl)-4-oxo(3-hydroquinazolin-3yl)]phenyl}carboxamide (6j)

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M.p.: 219C, Yield 70%; IR (KBr): 3315 cm (NH stretching, secondary amine), 3234 cm-1 (OH stretching, OH group), 3120 cm-1 (CH stretching, aromatic ring), 3053 (=CH stretching), 2909 cm-1 (CH stretching, CH3 group), 1716, 1729 cm-1 (C=O stretching, amide group), 1636, 1607 cm-1 (C=N, C=C stretching, aromatic ring), 1349 cm-1 (CN stretching, quinazoline ring), 866 (=CH bending), 920 cm-1 (ortho substitution of aromatic ring), 745 cm-1 (CCl stretching); 1H NMR (CDCl3): d 6.07.9 (m, 20H, ArH), 8.3 (s, 1H, CONH), 4.7 (s, 1H, C = CHAr), 5.8 (s, 1H, NCHS), 5.1 (s, 1H, ArOH); 13 C NMR (CDCl3): d 24.3, 63.4, 115.9, 120.8, 121.7, 122.4, 125.2, 125.6, 126.0, 126.8, 127.4, 127.7, 127.8, 128.7, 128.8, 129.1, 129.3, 129.4, 129.8, 133.0, 31.1, 133..5, 134.5, 136.1, 139.8, 151.2, 156.9, 160.5, 164.2, 164.3, 164.7; GCMS: m/z: 670.14 (M?). Anal. calcd. for

M.p.: 181C, Yield 63%; IR (KBr): 3313 cm-1 (NH stretching, secondary amine), 3234 cm-1 (OH stretching, OH group), 3120 cm-1 (CH stretching, aromatic ring), 3059 (=CH stretching), 2903 cm-1 (CH stretching, CH3 group), 1712, 1723 cm-1 (C=O stretching, amide group), 1632, 1614 cm-1 (C=N, C=C stretching, aromatic ring), 1340 cm-1 (CN stretching, quinazoline ring), 858 (=CH bending), 923 cm-1 (ortho substitution of aromatic ring); 1H NMR (CDCl3): d 6.67.9 (m, 20H, ArH), 8.4 (s, 1H, CONH), 4.8 (s, 1H, C=CHAr), 5.9 (s, 1H, NCHS); 5.1 (s, 1H, ArOH), 5.0 (s, 1H, ArOH), 3.7 (s, 3H, ArOCH3). 13C NMR (CDCl3): d 24.3, 55.8, 63.4, 101.9, 106.8, 108.8, 115.9, 120.8, 121.7, 122.4, 125.2, 125.6, 126.0, 127.4, 127.7, 128.8, 129.1, 129.3, 129.8, 133.5, 134.5, 136.1, 139.8, 151.2, 156.9, 159.3, 161.2, 160.6, 164.3, 164.5, 164.5; GCMS: m/z: 682.18 (M?). Anal. calcd. for C39H30N4O6S: C-68.61

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%, H-4.43%, N-8.21%. Found: C-68.66%, H-4.49%, N-8.26%. Physical constants and characterization of N-{5-[(2methoxyphenyl)methylene]-2-(4-hydroxyphenyl)-4oxo(1,3-thiazolidin-3-yl)}{4-[2-(4-methylphenyl)-4oxo(3-hydroquinazolin-3-yl)]phenyl}carboxamide (6k) M.p.: 99C. Yield 69%; IR (KBr): 3314 cm-1 (NH stretching, secondary amine), 3233 cm-1 (OH stretching, OH group), 3122 cm-1 (CH stretching, aromatic ring), 3051 (=CH stretching), 2903 cm-1 (CH stretching, CH3 group), 1713, 1725 cm-1 (C=O stretching, amide group), 1630, 1613 cm-1 (C=N, C=C stretching, aromatic ring), 1346 cm-1 (CN stretching, quinazoline ring), 863 (=CH bending), 921 cm-1 (ortho substitution of aromatic ring); 1 H NMR (CDCl3): d 6.17.9 (m, 18H, ArH), 8.3 (s, 1H, CONH), 4.7 (s, 1H, C=CHAr), 5.9 (s, 1H, NCHS), 5.1 (s, 1H, ArOH), 3.7 (s, 3H, ArOCH3); 13C NMR (CDCl3): d 24.3, 56.2, 63.4, 114.2, 114.9, 115.9, 120.8, 121.0, 121.7, 122.4, 125.2, 125.6, 126.0, 127.4, 127.7, 128.8, 129.0, 129.1, 129.3, 129.8, 133.5, 134.5, 136.1, 139.8, 151.2, 156.9, 157.6, 160.6, 164.2, 164.3, 164.6; GCMS: m/z: 666.74 (M?). Anal. calcd. for C39H30N4O5 S: C-70.25%, H-4.54%, N-8.40%. Found: C-70.29%, H-4. 59%, N-8.46%. Physical constants and characterization of N-{5-[(5bromo-2-hydroxyphenyl)methylene]-2-(4hydroxyphenyl)-4-oxo(1,3-thiazolidin-3-yl)}{4-[2-(4methylphenyl)-4-oxo(3-hydroquinazolin-3-yl)]phenyl}carboxamide (6l)

Physical constants and characterization of N-{5-[(2,6dichlorophenyl)methylene]-2-(4-hydroxyphenyl)-4oxo(1,3-thiazolidin-3-yl)}{4-[2-(4-methyl- phenyl)-4oxo(3-hydroquinazolin-3-yl)]phenyl}carboxamide (6m) M.p.: 183C, Yield: 72%; IR (KBr): 3319 cm-1 (NH stretching, secondary amine), 3230 cm-1 (OH stretching, OH group), 3123 cm-1 (CH stretching, aromatic ring), 3048 (=CH stretching), 2903 cm-1 (CH stretching, CH3 group), 1716, 1728 cm-1 (C=O stretching, amide group), 1632, 1614 cm-1 (C=N, C=C stretching, aromatic ring), 1349 cm-1 (CN stretching, quinazoline ring), 869 (=CH bending), 925 cm-1 (ortho substitution of aromatic ring), 752 cm-1 (CCl stretching); 1H NMR (CDCl3): d 6.27.7 (m, 19H, ArH), 8.4 (s, 1H, CONH), 4.9 (s, 1H, C=CHAr), 5.7 (s, 1H, NCHS), 5.3 (s, 1H, ArOH); 13 C NMR (CDCl3): d 24.3, 63.4, 115.9, 120.8, 121.7, 122.4, 125.2, 125.6, 126.0, 126.8, 127.4, 127.7, 128.8, 129.1, 129.3, 129.8, 130.8, 132.5, 133.5, 134.5, 135.7, 136.1, 139.8, 151.2, 156.9, 160.8, 164.0,164.4, 164.8; GCMS: m/z: 704.15 (M?). Anal. calcd. for C36H26 Cl2N4O4S: C-64.68%, H-3.71%, N-7.94%. Found: C-64. 73%, H-3.76%, N-7.99%. Physical constants and characterization of N-{5-[(4chlorophenyl)methylene]-2-(4-hydroxyphenyl)-4oxo(1,3-thiazolidin-3-yl)}{4-[2-(4-methylphenyl)-4oxo(3-hydroquinazolin-3-yl)]phenyl}carboxamide (6n)

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M.p.: 150C, Yield 71%; IR (KBr): 3313 cm-1 (NH stretching, secondary amine), 3234 cm-1 (OH stretching, OH group), 3120 (CH stretching, aromatic ring), 3057 (=CH stretching), 2907 cm-1 (CH stretching, CH3 group), 1718, 1727 cm-1 (C = O stretching, amide group), 1634, 1612 cm-1 (C=N, C=C stretching, aromatic ring), 1340 cm-1 (CN stretching, quinazoline ring), 867 (=CH bending), 926 cm-1 (ortho substitution of aromatic ring), 556 cm-1 (CBr stretching); 1H NMR (CDCl3): d 6.38.1 (m, 19H, ArH), 8.5 (s, 1H, CONH), 4.7 (s, 1H, C= CHAr), 5.8 (s, 1H, NCHS), 5.1 (s, 1H, ArOH), 4.9 (s, 1H, ArOH); 13C NMR (CDCl3): d 24.3, 63.4, 115.9, 115.6, 118.0, 118.7, 120.8, 121.7, 122.4, 125.2, 125.6, 126.0, 127.4, 127.7, 128.8, 129.1, 129.3, 129.8,131.3, 132.2, 133.5, 134.5, 136.1, 139.8, 151.2, 156.9, 157.3, 160.9, 164.1, 164.3, 164.6; GCMS: m/z: 730.09 (M?). Anal. calcd. for C38H27BrN4O5S: C-62.38%, H-3.72%, N-7.66%. Found: C-62.42%, H-3.77%, N-7.71%.

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M.p.: 209C, Yield: 68%; IR (KBr): 3317 cm-1 (NH stretching, secondary amine), 3235 cm-1 (OH stretching, OH group), 3125 cm-1 (CH stretching, aromatic ring), 3055 (=CH stretching), 2905 cm-1 (CH stretching, CH3 group), 1716, 1728 cm-1 (C=O stretching, amide group), 1637, 1615 cm-1 (C=N, C=C stretching, aromatic ring), 1348 cm-1 (CN stretching, quinazoline ring), 925 cm-1 (ortho substitution of aromatic ring), 859 (=CH bending), 742 cm-1 (CCl stretching); 1H NMR (CDCl3): d 6.17.9 (m, 20H, ArH), 8.5 (s, 1H, CONH), 4.8 (s, 1H, C=CHAr), 5.8 (s, 1H, NCHS), 5.0 (s, 1H, ArOH); 13 C NMR (CDCl3): d 24.3, 63.4, 115.9, 120.8, 121.7, 122.4, 125.2, 125.6, 126.0, 127.4, 127.7, 127.8, 128.7, 128.8, 129.1, 129.3, 129.8, 133.3, 133.5, 134.5, 136.1, 139.8, 151.2, 156.9, 160.7, 164.2, 164.3, 164.7; GCMS: m/z: 670.14 (M?). Anal. calcd. for C38H27ClN4O4 S: C-68.00%, H-4.05%, N-8.35%. Found: C-68.06%, H-4. 09%, N-8.41%.
Acknowledgment The authors express their sincere thanks to the Head, Department of Chemistry and to Bhavnagar University, Bhavnagar for providing research facilities.

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