Heteroatom Chemistry Volume 15, Number 1, 2004

Imidazole, and Sulfonamide Derivatives of Pyrazolo[3,4-d ]pyrimidine
M. M. Ghorab,1 Zeinab H. Ismail,2 Soad M. Abdel-Gawad,2 and Anhar Abdel Aziem2
1

Antimicrobial Activity of Amino Acid,

Department of Drug Radiation Research, National Centre for Radiation Research and Technology, P.O. Box 29, Nasr City, Cairo, Egypt Department of Chemistry, Faculty of Science (Girl’s), Al-Azhar University, Cairo, Egypt

2

Received 19 May 2003; revised 17 July 2003

ABSTRACT: Derivatives of pyrazolo[3,4-d]pyrimidine with amino acid 3a–d, imidazole 4a–d, carbonyl 6–9, pyrazole 10, pyrazolone 11, and sulfonamide 12–17 moieties were synthesized. Structure of the new compounds were established by their elemental analyses and spectral data. Some of the synthesized compounds were tested in vitro for their antimicrobial activity. Compounds 4b, 12, and 16 were almost as potent as the standard antibiotic Chloramphenicol as positive control. Also, compounds 3b, 3c, 12, and 16 were nearly as active as Terbinafine as positive control. C 2003 Wiley Periodicals, Inc. Heteroatom Chem
15:57–62, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10212

tion, sulfonamides have been widely used as bacteriostatic agents [8,9]. Having the above facts in mind and in continuation of our efforts to synthesize heterocyclic compounds containing pyrazolo[3,4d]pyrimidine [10], the present work was aimed at new pyrazolo[3,4-d]pyrimidine derivatives expected to have antimicrobial activity.

Syntheses
When the chloro compound 1 [12] was allowed to react with the sodium salt of various amino acids under reflux at pH 9–9.5, the corresponding N(7-phenylpyrazolo[3,4-d]pyrimidin-4-yl)amino acids 3a–d were afforded (Scheme 1). The structure of 3a–d were supported by elemental analyses, IR, 1 H NMR, and mass spectral data. The structure of products showed ␯ NH and ␯ C O in the 3400–3150 and 1720–1690 cm−1 regions respectively, in addition to another band in the 1254– 1124 cm−1 region for a COOH group [13]. The IR spectrum of 3a showed bands at 3398 (OH), 3220 (NH), 3101 (CH arom.), 1720 (C O), 1666, 1608 (2C N), 1230 cm−1 (CO2 H). Its 1 H NMR spectrum in (DMSO-d6 ) exhibited signals at δ 4.2 [s, 2H, ␣-CH2 ], 7.2–7.6 [m, 5H, Ar H], 8.2 [s, 1H, NH], 8.4 [s, 1H, CH pyrazole], 8.5 [s, 1H, CH pyrimidine], 8.8 [s, 1H, OH]. The IR spectrum of 3b revealed bands at 3309– 2507 (OH), 3309 (NH), 3055 (CH arom.), 2931 (CH
57

INTRODUCTION
A considerable number of pyrazolo[3,4-d]pyrimidines are known to be bioactive. They display antibacterial [1], antifungal [2], antimicrobial [3], antitumor [4], antiviral [5], and antipyretic [6] activities. Compounds having amino acid moieties are also known to possess a wide range of biological and pharmacological activity [7]. In addiCorrespondence to: M. M. Ghorab; e-mail: ghorabmoustafa@ hotmail.com. c 2003 Wiley Periodicals, Inc.

CH3 ]. 8.9 [t.). 3100 (CH arom. The IR spectrum of 6 showed bands at 3200 (NH). 1647 cm−1 (C N). 2H. 5H. The amino acid derivatives 3a–d were then cyclized with acetic anhydride in the presence of anhydrous sodium acetate [14] to give the imidazol derivatives 4a–d.6%).1 [d. 1H.1 [m. SCHEME 1 aliph. 2923 (CH aliph.). 168 (31. 235 (13. CH2 ]. Ar H]. NH]. 2191 (C≡N).5%). 1H. 7. 3116 (NH). 8. 8. 1697 (C O). 3047 (CH arom.1%).7 [s. 2H.0 [m.1%). 5H. 1H. with . ␣CH]. OH].9%). CH2 ethyl]. NH]. The IR spectrum of 4a showed bands at 2940 (CH aliph. 3062 (CH arom. 1H.5 [s. 8.6 [t. The IR spectrum of 8 showed bands at 3417 (NH). 7. 7.).3–8.6%).).9%). 51 (91.2 [m. 8.). Ar H]. ␤-CH]. and mass spectral data. 1H. ␥ -CH3 ]. 8. Thus. ␤-CH2 ].2 [m. 1H. 1600 cm−1 (C N). 1218 cm−1 (CO2 H). Compound 1 reacted with active methylene compounds (malononitrile.8%).2 [m. 116 (19.).7 [q. 153 (4. CH pyrazole + CH pyrimidine].4–8. other significant peaks appeared at 264 (M-1.5 [d. The IR spectra showed the disappearance (C≡N) and presence (NH. 3047 (CH arom. 3039 (CH arom. 8. 5H. 2931 (CH aliph.3. 8. 6H. 7. 3. 1712 (C O). 3047 (CH arom. ethyl cyanoacetate. 1627 (C N).7 [s.6%). 1674 (C O).8 [s.3–8.6%). ethylacetoacetate. 3H.7 [2s. CH pyrazole + CH pyrimidine]. 1H. 1H. 1H. 236 (91. 5H.3%). 3055 (CH arom.5 [s. CH pyrimidine]. CH pyrazole].3 [s. 7. 1596 cm−1 (C N). 5H. 132 (7.). CH pyrazole + CH pyrimidine]. Ar H].72%). 3224 (NH). 2923 (CH aliph. 8. 2CH3 ]. OH]. 4. 8. 2930 (CH aliph. CH pyrazole]. 8.4 [2s. 2923 (CH aliph. 2H. other significant peaks appeared at 281 (7. 8.3 [m. 5H. 6H. NH2 ) of bands.5%).).3–7.2 (m. NH2 ). 1735 (C O). 1751 cm−1 (C O). 1H.6 [2s. Ar H]. 1H.4 [2s. 263 (36. The postulated structures were confirmed by IR.8%). CH2 ].6 [d. ␣-CH]. COCH3 ]. 8. 1 H NMR spectrum of 4d in (DMSO-d6 ) revealed bands at 0. CH3 ]. Ar H]. 3H.4 [br. 4. 8.6. 1596 (C N). 1710 (C O) 1573 cm−1 (C N). 1 H NMR spectrum of 4a in (DMSO-d6 ) exhibited signals at δ 1. 1620 (C N). The mass spectrum of 3c revealed a molecular ion peak m/z 299 (M+ . It is reported that ␤-enaminonitriles reacted with hydrazine to afford pyrazole derivatives [15].6 [s. 2H.5 [s. 8. 8.). 1H.3 [t. 4. ␣-CH]. 1H. 1242 cm−1 (CO2 H).2. 1712 (C O).5%). Ar H]. CH pyrazole + CH pyrimidine]. 2H.0 [q. 2H. Its IR spectra showed the absence of (NH) band.5. ␣-CH]. 1710 (C O). 2221 (C≡N).9 [q. 3H. 7.4–8. The IR spectrum of 4d revealed bands at 2970 (CH aliph. 141 (32. 8. 2CH3 ]. The IR spectrum of 3c exhibited bands at 3400–2507 (OH). 1H. The mass spectrum of 10 exhibited a molecular ion peak m/z 292 (M+ . 1712 (C O). Ar H]. NH]. 4. 5H. CH3 ethyl]. with a base peak at 263.3%). 2931 (CH aliph. 5. 2. NH]. 7.). 195 (77.5 [s. acetylacetone. 1H. with a base peak at 77.). Its 1 H NMR spectrum in (DMSO-d6 ) showed signals at δ 1. The IR spectrum of 10 showed bands at 3260. respectively. 1H. The IR spectrum of 7 showed bands at 3417 (NH). CH pyrazole + CH pyrimidine]. The IR spectrum of 3d showed bands at 3317 (OH). CH pyrimidine].2 [q. 8.3 [t.).3–8. 6H.8 [m. 1H. Its 1 H NMR spectrum in (DMSO-d6 ) showed signals at δ 1. 1666. OH]. 2.7 [s. 1658 cm−1 (C N). 1. The IR spectrum of 9 exhibited bands at 3163 (NH). 8.7%). 1 H NMR spectrum of 4c in (DMSO-d6 ) exhibited signals at δ 1.3. 2H. Ar H]. 12.3 [t. 1 H NMR. 7.).). treatment of 5 and 6 with hydrazine hydrate in boiling ethanol furnished the pyrazole 10 and pyrazolone 11 respectively (Scheme 2).2–8. 2CH2 ].).9 [d. 15. NH]. The IR spectrum of 4b showed bands at 3101 (CH arom.2 [m. 1 H NMR spectrum of 3b in (DMSO-d6 ) revealed signals at δ 1.9%). 1643 cm−1 (C N). 221 (4. 2. 2H. 5. 3H. 5H. 1218 cm−1 (CO2 H). The IR spectrum of 4c showed bands at 3394 (OH). 8.58 Ghorab et al. 11. The 1 H NMR spectrum of 8 in (DMSOd6 ) revealed signals at δ 0. 7. 1651. 2962 (CH aliph.0 [m. Its 1 H NMR spectrum (DMSO-d6 ) showed signals at δ 1.9 [s.). 2.0–7.5 [d. 2H. and diethylmalonate) to afford the corresponding 4-alkylpyrazolopyrimidine derivatives 5–9. 1H. The mass spectrum of 4b exhibited a molecular ion peak m/z 265 (M+ .5 (s. 75 (1. 1735 (C O). 2H.4 [s.).5 [m. The IR spectrum of 5 showed bands at 3429 (NH). 4H.). CH pyrazole + CH pyrimidine]. 3200 (NH. 211 (61.0 (2s. ␤-CH]. 1596 cm−1 (C N). 8. 1658 cm−1 (C N).

NHSO2 ].4%).6 [s. 3421 (NH. 10. NH]. 2H. 3078 (CH arom.0%). and other significant peaks appeared at 365 (M-1. 1H. 2NH]. NH2 ). 5H. The IR spectra (KBr) were measured on a Shimadzu IR 110 spectro-photometer.6. 2H. 1H. AB system]. and Sulfonamide Derivatives of Pyrazolo[3. 8. Its 1 H NMR spectrum in (DMSO-d6 ) showed signals at δ 7.9. 9.3 [s.8%). The IR spectrum of 16 showed bands at 3309. 3217 (NH).8 [m.6.1%). NH2 ].5 [s. CH pyrazole + CH pyrimidine].6%). 4H. 2H. CH pyrazole + CH pyrimidine]. 8.6%). NH].8–8. 10. The mass spectrum of 13 showed a molecular ion peak m/z 408 (M+ .6.3. 129 (5. NH].5 [s. 3400.5 [s.). 8. 1H. 1H. 7.7%). 1 H NMR spectra were obtained on a Bruker proton NMR-Avance 300 (300. with a base peak at 77. 4H. 286 (11. 10. 3124 (2NH). conducting this reaction in presence of anhydrous K2 CO3 [20] afforded sulfanilamide derivative 17 (Scheme 3).1%).6.7 [2s. 211 (11. 4H. 53. 8. 1581 cm−1 (C N).2 [s.7 [2s. 4H.1 [2d.2 [2d. 156 (10.8%). 1635 cm−1 (C N).1%). A literature survey revealed that because of their biological activities sulfonamides have enormous potential as pharmaceutical and agricultural agents. 1H.2%). 1627 cm−1 (C N). 3213 (NH. 10. NH2 ).). Condensation of 1 with some sulfonamides in N. 8. AB system]. 1H. 8. 2H. 230 (2. CH isoxazole]. 8. NH2 ].4 [2d.8 [s. 6H.6 [2s. 2H. 75 (8.Antimicrobial Activity of Amino Acid. The IR spectrum of 14 revealed bands at 3309. 77 (28. 3H.8 [m. The mass spectrum of 17 showed a molecular ion peak m/z 366 (M+ . Imidazole. 7. AB system].9–8. 3332. 1640 cm−1 (C N). 6. 11. Ar H]. and antiinflammatory [19] properties. 90 (17. 129 (12. CH3 ]. 91 (8. 3139 (NH).8 [m. 7.9%). 2H. Elemental analyses were carried at the microanalytical laboratories of the Faculty of Science. 1 H NMR spectrum of 11 in (DMSO-d6 ) exhibited signals at δ 7. 1627 cm−1 (C N).4 [s.3%).9. 8. 1627 (C O).N-dimethylformamide (DMF) gave only the sulfonamide derivatives 12–16. 3070 (CH arom. Cairo University. using tetramethylsilane (TMS) as internal standard. CH pyrazole + CH pyrimidine].5%). 1 H NMR spectrum of 17 in (DMSOd6 ) revealed signals at δ 6.2. 3217 (NH. in DMSO-d6 as a solvent. 1674 (C O). The IR spectrum of 12 showed bands at 3301.7 [2s.2%).2 [s. 8. 302 (2.). 75 (17. 158 (3. 182 (0. NHSO2 ]. 9. 8. 1 H NMR spectrum of 16 in (DMSO-d6 ) revealed signals at δ 2. EXPERIMENTAL All melting points are uncorrected. 2CH3 ]. 3271 (NH.9%).3–7. Its 1 H NMR spectrum exhibited signals at δ 2. The IR spectrum of 15 showed bands at 3340. 5H. Ar H + NH2 ]. 2H.4%). 8.2. NHSO2 ]. CH pyrazole + CH pyrimidine]. 2923 (CH aliph. 7H. AB system].4 [m. The IR spectrum of 17 showed bands at 3430. 5H. NH2 ).7 [2s. whereas. and other significant peaks appeared at 226 (3.6 [s.5 [2s.3–8 [m. 183 (10. 1596 cm−1 (C N). 7. 8. antitumor [18]. 7. 2H.7 [s. The IR spectrum of 13 showed bands at 3433. and other significant peaks appeared at 286 (26. antifungal [17]. 11.7%). 1H.4-d ]pyrimidine 59 SCHEME 3 SCHEME 2 a base peak at 211. They are associated with antibacterial [16]. 7.6 [br. Mass spectra were run on HP Model MS-5988.6%).2–7. NH2 ). CH pyrazole + CH pyrimidine). . 30.2 [2d. Ar H]. 1H. 6. 7. 8. The IR spectrum of 11 revealed bands at 3450. 1627 cm−1 (C N). 28.3–7. 5H. Ar H]. Ar H]. with a base peak at 365. MHz). CH pyrimidine].1%). 7.

70) 27.96 (62.43) 62.00) 3. The chloro derivative 1 (4.19) 59.28 (17.23 (4.22) 4. The chloro derivative 1 (0.32) 64.82 (3.90) 3.79) 32.4-d]pyrimidin-4-yl)1.59 (4. 6 (10 mmol). 3-(1-Phenyl-1.94 (52. The solvent was removed and the residue washed with water.91 (3. 3-Oxo-2-(1-phenyl-1. acetic anhydride (5 ml).10) 4.15) 56. 2-(1-Phenyl-1.23 (4. and poured into ice/HCl 4-(1-Phenyl-1H-pyrazolo[3.73 (24.11) 33. and 2-(Phenyl-1. The separated solid was filtered off. washed with water.4-d]pyrimidin-4-ylidene)butyric Acid Ethyl Ester 8.58 (3.09) 50.90) 24.80) 58.50) 23.2-dihydro-pyrazol-3-one 11 A mixture of 5.15 (62.20) 22.0) 4. (◦ C) 3a 3b 3c 3d 4a 4b 4c 4d 5 6 7 8 9 10 11 12 13 14 15 16 17 223–225 174–176 205–207 115–117 278–280 250–252 335–337 337–239 >300 261–263 308–310 309–311 307–309 76–78 197–199 268–270 298–300 263–265 250–252 188–190 194–196 Yield (%) 82 74 76 88 71 75 75 75 56 74 90 92 87 88 75 80 95 87 90 89 80 Mol.36 (59.30) 27.07 (3.92 (21. TABLE 1 Physical and Analytical Data of the Synthesized Compounds Required (Found) (%) m.95 (22.89) 57.70) 23.00) 61.50) 22.73 (55.15 (4.54 (62.93 (4.41 (23.56 g of sodium in 50 ml ethanol) and stirred for 2 h.50) 23.00) 3.08 (4.10 (3.74) 56.5-dihydro-pyrazolo[3.73 (61.82 (3.60 mmol) and sodium carbonate (5.78 (59. mixture. Wt. The extracted solvent was dried over anhydrous magnesium sulphate and removed under reduced pressure to afford 7.p.4-d]pyrimidin-4-ylidene)pentane-2.58) 26.89 (23.5-dihydropyrazolo[3.00) 62. dried.72 (23.21) 24.11) 55.68) 3.80) 57.30 (32.35 (38.4-d]pyrimidin-4-yl)1H-pyrazole-3.3 :4.40 mmol) were dissolved in water (10 ml).75 (3.1-c]imidazoles 4a–d A mixture of 3a–d (10 mmol). Formula (Mol. and crystallized from ethanol to give 5 and 6 respectively (Table 1).76) 61.92 (3. washed with water.5-dihydro-pyrazolo[3.80 (3. The ethanol was removed under reduced pressure and the residue was poured into 100 ml of cooled water and extracted with chloroform.4-dione 7.46 (5.4-d]pyrimidin-4-ylidene)malonic Acid Diethyl Ester 9 Acetylacetone or ethyl acetoacetate and/or diethylmalonate (0. 2-Substituted 3-Oxo-7-phenylpyrazolo[2 .00 (49.11) 22.70) .41 (26.24) 65.50 (22.73 (55. The solid product obtained was filtered off.52) H 4.22) 3.11 (5.34 (4.50) 52.58) 65.80 mmol) was then added and the mixture was stirred at 100◦ C for 6 h at controled pH.30 (65.30) 4.30) 4.56) 4.15) 21.4-d]pyrimidin-4-ylidene)acetic Acid Ethyl Ester 6 A solution of 1 (10 mmol) and malononitrile or ethyl cyanoacetate (10 mmol) in pyridine (20 ml) was refluxed for 5 h.99 (57.52 (65.53) 3.4-d]pyrimidin-4-yl) amino Acids 3a–d Amino acid (9. filtered.18 (56.88 (27.76 (4. The reaction mixture was left overnight at room temperature. N-(7-Phenyl-pyrazolo[3.50) 22. and 9 respectively (Table 1).37 (56.53 (57. then cooled.01 (60.00) 3.60) N 26. 8.33 (23.08 (4. then treated with formic acid (88%).5. and crystallized from dioxane to give 3a–d (Table 1).60) 55.95 (22.02 mol) was added to an ethanolic sodium ethoxide solution (0.69) 59.60 Ghorab et al.5-dihydro-pyrazolo[3.01) 5.) C13 H11 N5 O2 (269) C14 H13 N5 O2 (283) C14 H13 N5 O3 (299) C16 H17 N5 O2 (311) C13 H9 N5 O (251) C14 H11 N5 O (265) C14 H11 N5 O2 (281) C16 H15 N5 O (293) C14 H8 N6 (260) C16 H13 N5 O2 (307) C16 H14 N4 O2 (294) C17 H16 N4 O3 (324) C18 H18 N4 O4 (354) C14 H12 N8 (292) C14 H11 N7 O (293) C17 H14 N6 O2 S (366) C18 H16 N8 O2 S (408) C21 H17 N7 O3 S (447) C20 H16 N8 O3 S2 (480) C23 H20 N8 O2 S (472) C17 H14 N6 O2 S (366) C 57.91 (24.00) 63.5]pyrimido[6.39 (63.00) 4.68) 23.44 (33.47 (58.80) 62.33 (3.80) 17.02 (25. and crystallized from DMF-EtOH to give 4a–d (Table 1).00) 15.63) 3.33 (57.02 mol) was added and the reaction mixture was heated under reflux on a water bath for 5 h. then adjusted to pH 9–9. and anhydrous sodium acetate (10 mmol) was heated under reflux for 3 h.5-diamine 10 and 5-Amino-4(1-phenyl-1H-pyrazolo[3.04 (18.63) 5.61 (64.4-d]pyrimidin-4-ylidene)malononitrile 5 and Cyano-(1-phenyl-1.55) 19.88) 4.5-dihydropyrazolo[3.81 (15.50) 3. and hydrazine hydrate (10 mmol) in ethanol (20 ml) was refluxed for 6 h.80 (22.60) 38.71) 5.45 (27.

4-d ]pyrimidine 61 Well diameter: 1 cm (100 µl of each conc.5 1 5 + 0 + + ++ ++ ++ – 2. Candida albicans then allowed to cool. 2. pyrazolopyrimidine containing benzensulfonamide 12 and 16 showed high activity against Gramnegative bacteria.5 1 5 4-Amino-N-(1-phenyl-1H-pyrazolo[3.6–1. On the other hand.5 0 0 + 0 ++ ++ ++ – A mixture of 1 (10 mmol). Aspergillus flavus. subtilis.0 cm beyond control.1– 1.N-dimethylformamide (DMF). and to the pathogenic fungi Aspergillus fumigatus. + + + = nhibition values = 1. The reference antibiotic Chloramphenicol and fungicide Terbinafin were used as positive controls for comparison. The solid product was collected and crystallized from DMF-EtOH to give 12–16. respectively (Table 1). TABLE 2 Antimicrobial Activity of Some Newly Synthesized Compounds at Different Concentrations [mg/ml] Aspergillus fumigatus Pseudomonas aeruginosa The antimicrobial screening of some synthesized compounds was undertaken using the diffusion agar technique [21]. the Gram-negative bacteria Pseudomonas aeruginosa and Escherichia coli.5 cm beyond control. ++ = inhibition values = 0. Imidazole. and Sulfonamide Derivatives of Pyrazolo[3. Penicillium species. was tested). Pyrazolopyrimidine bearing imidazole 4b. and anhydrous K2 CO3 (1 g) was refluxed in DMF (30 ml) for 12 h. and poured into crushed ice. which showed no inhibition zones. Penicillium species Aspergillus flavus A mixture of the chloro derivative 1 (10 mmol) and sulfonamides (10 mmol) in N.5 cm beyond control.N-dimethylformamide (20 ml) was heated under reflux for 12 h and poured into crushed ice. 0 = not detected. The solid product was collected and crystallized from ethanol to give 10 and 11.5 4-(1-Phenyl-1H-pyrazolo[3.5 0 0 0 0 + + – + 1 + + + ++ ++ ++ 0 0 + + ++ + ++ + – – +++ +++ 5 2.1–0. then cooled. The solid product was collected and crystallized from DMF/H2 O to give 17 (Table 1).5 0 ++ 0 + + + 0 + ++ + + + ++ ++ ++ + + + – – 1 5 + + + + 0 0 + + + + 0 ++ ++ ++ + + + ++ + + + + ++ ++ ++ – – – ANTIMICROBIAL ACTIVITY 2.5 0 0 0 + + + – ++ 1 . aureus and B.4-d]pyrimidin4-ylamino)benzenesulfonamide Derivatives 12–16 + 0 ++ 0 0 0 + + + ++ + + – – ++ + + + 1 5 0 0 0 + ++ + ++ 2.5 0 0 ++ 0 ++ ++ ++ – 1 + + ++ + ++ +++ ++ – 5 0 0 ++ 0 ++ ++ ++ – 2. pyrazolopyrimidine having propionic acid 3b and benzenesulfonamide 12 and 16 exhibited good antifungal activity against Escherichia coli Bacillus subtilis Staphylococcus aureus 3b ++ 3c + 4b ++ 4c 0 12 +++ 16 ++ Chloramphenicol ++ Terbinafin – 5 + 0 ++ 0 ++ ++ ++ – 2.4-d]pyrimidin-4-yl)benzenesulfonamide Sulfanilamide 17 ++ + 0 0 +++ ++ – +++ ++ ++ + + + + 0 0 0 0 0 0 0 0 + 0 ++ + ++ ++ ++ + ++ + – – – – ++ ++ ++ ++ 1 5 2. sulfanilamide (10 mmol). + = inhibition values = 0. respectively (Table 1). and pyrazolopyrimidine bearing N-(4. In addition. The fungi cultures were maintained on Czapek’s Dox agar medium.Antimicrobial Activity of Amino Acid. pyrazolopyrimidine having benzenesulfonamide 12. The tested compounds were dissolved in N.6-dimethylpyrimidine) moiety 16 were found to be the most active compounds against Gram-positive bacteria S. and Candida albicans. Table 2 lists the screening results of the tested compounds against the Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis.

. H. 33. 33. T. Singhal. Zang. A. N. K. M. 50. C. K. (b) Petionin. albicans. E. B. K. B. 12. B. J Antibiot 1986. Eur J Med Chem 2000. 39. Dastidar.. D. R. 853. R.. Revankar. 18. Heterocycl Chem 1981. Mekernan.. C. Shukla.. 3b. M. K. 320. J. 221. Hidaka. 73. 920.. J. Egypt.. Kandel.. Srivastava. S. Elmoghayar. 1288. Sayed. Norton. O.. Dr. A. M. M.. A. K. M.. 27. E. Raichurkar.. for doing the antimicrobial activity of some synthesized compounds. J. [7] (a) Petionin.. K. N. J Heterocycl Chem 1980. 165.. 1291. while compound 12 and 16 revealed remarkable activity against A.. pp. ACKNOWLEDGMENT Many thanks are due to Prof. flavus. M.. J Indian Chem Soc 1982. H. M. Seibert. D. [14] Afify. El-Nady. Mahajanshetti. G. Reinhard. Shelar. Elgemeie. 93. Wiley: New York. J Gen Chem USSR 1963. A. 33. [18] Sondhi. R. [17] Misra.. Isono. Veenhuizen. Ishii. W.. S. R. J. F. M. Salunkh.. Reitz. Hokanson.. [11] Ghorab. Ilies. K. D. A. M. [15] Elnagdi... 12. 1277. C. Indian J Chem 1988. Cottam. Mohey. 39.. fumigatus. S.. White.. J Antibiot 1985. Jurca. A. 131. Kachare. D. A. 59. S.. [6] Elnagdi.. 3c. B. 743.. 3rd ed. M. P. P. [8] Zoni. S. J... C. [13] Bellamy. [12] Vishnu.. K. A. [2] Hasobe. W. Johar. D. D.. 275. Zh Obshch Khim 1963. J Heterocycl Chem 1990. El-Batal. Cogusch. Burton. M. . 140–162.. Adv Heterocycl Chem 1987. Arch Pharmacol 1998. R. H. L. Viemi. E. T. Cairo. Raghubir. A. [9] Supuran. Q. W. Also. Department of Drug Radiation Research. 781.. Acta Pharm 2000. Perkins. T. Cottam. Eur J Med Chem 1998. M. p. The Infrared Spectra of Complex Molecules. Blackwell Scientific Publications: Oxford. L. A.. H. Hrishi. 17. M. [3] Kitahara. [4] Anderson. E. K. Scozzafava. Dalley. Nimbalkar. and 16 were nearly as active as Terbinafin as positive control. Robins. 38.. 83. 28. 35. M. and 16 were almost as potent as the standard antibiotic Chloramphenicol as positive control. J Med Chem 1995. Watanabe.. H. S.. [16] Gadad. National Centre for Radiation Research and Technology. French. V. A. Finally.. P. A. I... 1975.. M. J Antibiot 1986. [20] Hogale. 331. B. R. REFERENCES [1] Kern.. P. H. 572. Monatsh Chem 2000.. Saneyoshi. Khodyreva. G. S.. [19] Li. S. R. Khodyreva. A. S. 1010. 64. Elfaham.. A. 511. Anderson. V. B. H. 314. G. V. G... V. compound 12 showed antifungal activity against C. 4570. M. R. 27B. Arnold.. 41. J Med Chem 1985. G. J Indian Chem Soc 1987. A. P. Phosphorus Sulfur Silicon 2000. Also compounds. 755.. L.. [10] Ghorab. B. 439. 38. J.62 Ghorab et al. Larson... K. J. 219. R. compounds 3b and 3c showed promising activity against Penicillium species. Saxena.. [21] Reeves. J. M. C. Principles of Methods of Assaying Antibiotic in Pharmaceutical Microbiology. K. R. Y. E.. D. S.. R. I.. Nord. M. Robins. Okazaki. [5] Petrie. Revankar. S.. K. These results indicated that the biologically active compounds 4b. G. 1983.