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Note
growth was noted after 24 and 48 hr. The lowest 62.63, H 4.89, N 12.91. IR(KBr): 1645 (>C=O),
concentration, which showed no growth after spot 1660(>C=O), 1590(>C=N), 3230(>N-H); 1H NMR: δ
subculture was considered as MBC/MFC for each 7.0-7.9 (m, 12H, ArH), 10.90 (s, 1H,-CONHa) 10.52
drug. The highest dilution showing at least 99% (s, 1H, -CONHb), 12.90 (s, 1H, -CONHc).
inhibition is taken as MBC/MFC. The result of this Aryl-N-(5-{4-[2-(2-chlorophenyl)-4-oxo(3-hydro-
test is affected by the size of the inoculum. The test quinazolin-3-yl)]phenyl} (1,3,4,thiadiazol-2-yl))
mixture should contain 108 organisms/mL. The amides 4a-l. Compound 3 (0.01 mole) was added to
standard drug used in the present study was cold conc. sulphuric acid (25 mL). The mixture was
gentamycin for evaluating antibacterial activity which stirred at room temp for 2 hr. The resultant solid mass
showed (0.25, 0.05, 0.5 and 1 μg/mL MBC against was poured onto crushed ice (100 g) with stirring. The
S. aureus, S. pyogenes and P. aeruginosa respectively. product was filtered, washed with water and dried.
K nystatin was used as the standard drug for The characterization data of compound 4a prepared
antifungal activity, which showed 100 µg/mL MFC according to this procedure was given in Table I, m.p.
against fungi, used for the antifungal activity. 145°C, yield : 70%. Anal. Found: C 64.87, H
Compounds 4e and 4i are considered to be active 3.20, N 12.80. Calcd. for C29H18ClN5O2S: C 64.98, H
against S. pyogenes. The antibacterial activity of both 3.38, N 13.06. IR(KBr): 1660(>C=O), 1696(>C=O),
compounds were enhanced due to the introduction of 1580(>C=N), 3156(>N-H); 1H NMR: δ 7.0-7.9 (m,
chloro and methyl group in the heterocyclic frame 12H, ArH), 12.80 (s, 1H, -CONH-). MS: [M+] at m/z
work. Compounds 4c was active against C. albicans 535.5 and other prominent peaks are appeared at
and A. clavatus. Due to the presence of nitro group 531.40, 413.27, 336.08, 256.31, 228.28, 202.19, 105,
consequently 4k is active against C. albicans and A. 81.03.
clavatus. The enhancement of the activity of this
compound is due to the presence of chlorine atom in Acknowledgement
the frame work. From the activity data, it was The authors express their sincere thanks to the
observed that minor change in molecular Head, Department of Chemistry, Bhavnagar
configuration of these compounds profoundly University, Bhavnagar for providing research
influences the activity. facilities.
Experimental Section References
Melting points for resultant compounds were 1 Robert J A & Russell H E, J Med Chem, 15, 1972, 335.
determined in open capillary tubes using a Toshniwal 2 Desai N C, Shah B R, Bhatt J J, Patel H H, Undavia N K &
melting point apparatus and are uncorrected. IR Trivedi P B, Indian J Chem, 34B, 1995, 201.
spectra were recorded in KBr on a FT IR 9201 VC 3 Desai N C, Undavia N K, Trivedi P B, Dave D & Vyas G D,
Indian J Chem, 36, 1998, 1280.
spectrophotometer; 1H NMR spectra in CDCl3 on 4 Khili M A, Soliman R, Furghuli A M& Bekhit A A, Arch
DRX (200 MHz) and DRX (300 MHz) spectrometer Pharm (Weighnein, Germany), 327, 1994, 27.
using TMS as internal standard. Mass spectra was 5 Gursoy A, Buyuktimkin S, Demirayak S & Ekinci A C, Arch
recorded on Q-TOF Micro Mass. Purity of these Pharm (Weighnein, Germany), 323, 1990, 623.
6 Panday V K, Misra D & Shukla S, Ind Drug, 31, 1994, 532.
compounds were checked by TLC. Compounds ethyl
7 Joshi V & Chardhari R P, Indian J Chem, 26B, 1987, 602.
4-[2-(2-chlorophenyl) -4-oxo-3-hydroquinazolin-3yl] 8 Wasfy A A F, Indian J Chem, 42B, 2003, 3102.
benzoate 1, and N-amino{4-[2-(2-chlorophenyl) -4- 9 Zilberminto LG, Bv Estestr Nauch Insti Permskmsk Univ,
oxo(3-hydroquinazolin-3yl]phenyl} carboxamide 2 141, 1964, 67; Chem Abstr, 64, 1966, 1220.
are given in literature20-24. 10 Seth P K & Parmar S S, Can J Pharmacol, 43, 1965, 1019.
11 Umino S, Kariyone K, Zenno H & Kamiya T, Japanese Pat,
Aryl-N-{[({4-[2-(2-chlorophenyl)-4-oxo(3-hydro- 12, 1970, 670; Chem Abstr, 68, 1968, 2195.
quinazolin-3-yl)]phenyl}carbonylamino)amino]- 12 Shetty B V, US Pat, 1970, 3,549,634; Chem Abstr, 75, 1971,
thioxomethyl}amides 3. Compound 2 (0.02 mole) 5940.
and aryl-isothiocyanate (0.02 mole) in dry acetone 13 Otto H & Houlohan w w, Swiss Pat, 1971, 499,544; Chem
Abstr, 75, 1971, 20435.
(20 mL) were stirred for an hr at room temp and
14 Panday V K, Lohani H C, Shanker K, & Dovel D C, Indian
further washed with water and dried to generate 3a, Drugs, 20, 1983, 315.
m.p. 130°C, yield : 67%. Anal. Found: C 62.87, 15 Pandey V K, Gupta M & Mishra D, Ind Drugs, 33, 1996, 409.
H 3.60%, N 12.89. Calcd for C29H20ClN5O3S: C 16 Sen Gupta A K, & Misra Hemant K, Indian J Pharm Sci,
69(11), 1980, 1313.
NOTES 3
17 Mosad S M, Mohammed K I, Ahmed M A & Abdel-Hamide S 23 Desai N C, Bhatt J J, Patel H H, Undavia N K & Trivedi P B,
G, J Apllied Sci, 4 (2), 2004, 302. Indian J Chem, 34B, 1995, 201.
18 Trova M P, Zhang N & Kitchen D B, Chem Abstr, 129, 1982, 24 Shivarama B H, Prasanna C S, Roy K S, Shridhra K & Bhat U
41144a. G, Indian J Chem, 43B, 2004, 2174.
19 Udupi R H, Ramesh B & Bhatt A R, Indian Heterocycl Chem, 25 Robert C, Medical Microbiology, ELBS and E & S., Living
8, 1999, 301. stone, Briton 11th edn., 1970, 895-901.
20 Pandey V K, Pathak L P M & Mishra S K, Indian J Chem, 26 National committee for clinical laboratory standard:
44B, 2005, 1940. Reference method for broth dilution antifungal susceptibility
21 Desai N C, Shah M D, Keshav K A, Saxena A K, Indian J testing of yeasts approved standard M27A, NCCLS, Wayne
Chem, 40B, 2001, 201. PA, 1997.
22 Desai N C, Bhatt J J, Shah B R, Undavia N K & Trivedi P B,
IL Farmaco, 51(5), 1996, 361.
1
Compd Ar m.p Yield Found (%) Calcd H NMR (CDCl3) (δ, ppm)
°C (%) C H N S
1 - 120 60 68.23 4.23 5.43 7.1-8.0 (m, 12H, ArH), 4.29 (t, 2H,
(68.15 4.18 5.40) -OCH2-)
2 - 170 62 64.53 3.86 14.33 7.1-7.95 (m, 12H, ArH), 8.0 (s, 1H,
(64.49 3.73 14.20) -CONH-), 2.0 (s, 2H, -NH-NH2)
3 C6H5 130 67 62.63 4.89 12.91 5.55 7.0-7.9 (m, 12H, ArH), 10.90 (s, 1H,-
(62.87 3.60 12.89 5.51) CONHa), 10.52 (s, 1H, -CONHb), 12.90 (s,
1H, -CONHc)
4a C6H5 145 70 64.98 3.38 13.06 5.98 7.0-7.9 (m, 17H, ArH), 12.80 (s, 1H,
(64.87 3.20 12.80 5.95) -CONH-)
4b C6H5-CH2 178 65 65.51 3.66 12.73 5.83 7.0-7.9 (m, 17H, ArH), 12.49 (s, 1H,
(65.48 3.60 12.65 5.81) -CONH-), 3.44 (s, 2H, -COCH2-Ar)
4c m-NO2-C6H5 192 67 59.95 2.49 12.33 5.51 7.17-8.1 (m, 16H, ArH), 12.9 (s, 1H,
(59.91 2.30 12.23 5.45) -CONH-)
4d o-Cl-C6H5 173 72 61.06 3.00 12.27 5.62 6.94-7.8 (m, 16H, ArH), 12.7 (s, 1H,
(61.05 2.98 12.11 5.61) -CONH-)
4e m-Cl-C6H5 180 65 61.06 3.00 12.29 5.62 7.42-7.9 (m, 16H, ArH), 12.8 (s, 1H,
(61.04 2.95 12.13 5.60) -CONH-)
4f p-Cl-C6H5 162 77 61.06 3.00 12.25 5.62 6.50-7.8 (m, 16H, ArH), 12.8 (s, 1H,
(61.03 2.99 12.20 5.60) -CONH-)
4g o,m-Cl2-C6H3 162 77 57.58 2.66 11.57 5.30 7.32-8.1 (m, 15H, ArH), 12.7 (s, 1H,
(57.55 2.64 11.42 5.28) -CONH-)
4h C8H4NO2-CH2 162 59 62.08 3.09 13.57 5.18 7.88-8.0 (m, 16H, ArH), 12.5 (s, 1H,
(62.04 3.05 13.42 5.15) -CONH-), 4.50 (s, 2H, -COCH2-N)
4i p-CH3-C6H5 192 85 65.51 3.66 12.73 5.83 7.2-7.8 (m, 16H, ArH), 12.6 (s, 1H,
(65.50 3.62 12.60 5.80) -CONH-), 2.35 (s, 3H, Ar-CH3)
4j p-OCH3-C6H5 142 65 63.65 3.56 12.11 5.66 7.2-7.8 (m, 16H, ArH), 12.8 (s, 1H,
(63.60 3.50 12.01 5.62) -CONH-), 3.95 (s, 3H, Ar-OCH3)
4k p-NO2-C6H4-CH2 183 79 60.55 3.21 12.11 5.38 7.5 -8.1 (m, 16H, ArH), 12.7 (s, 1H,
(60.52 3.20 12.01 5.35) -CONH-), 3.46 (s, 2H, Ar-CH2 -CO)
4l p-Cl-C6H4-CH2 174 67 61.64 3.27 12.34 5.48 7.0 -7.9 (m, 16H, ArH), 12.5 (s, 1H,
(61.63 3.20 12.24 5.44) -CONH-), 3.44 (s, 2H, Ar-CH2 -CO)
R = 2-Chlorophenyl
4 INDIAN J. CHEM., SEC B, MARCH 2007
Antibacterial activity is expressed in the form of Minimal Antifungal activity is expressed in the form of
Bactericidal Concentration (MBC) Minimum Fungicidal Concentration (MFC)
Compd E. coli P. aeruginosa S. aureus S. pyogenus C. albicans A. niger A. clavatus
MTCC MTCC MTCC MTCC MTCC MTCC MTCC
443 1688 96 442 227 282 1323
NHNH2
COOC2H5
O O O
N NH2NH2 H2O N
Methanol
N R N R
1 2
O Anhydrous
acetone
O
Ar-NCS
O NHa Ar
bHN NHc
N
S
N R
3
H2SO4
Room temperature
O
S
N NH
N N
N O Ar
R 4
Scheme 1
Graphical abstract:
Several Aryl-N-(5-{4-[2-(2-chlorophenyl)-4-oxo(3-hydroquinazolin-3-yl)]phenyl} (1,3,4,thiadiazol-2-yl))amides 4a-l have been prepared
and tested for their antibacterial and antifungal activities.
O CH3 NH
NH2
NH2NH2 H2O CS2, KOH
O O C2H5OH
NO2 NO2
S
NH
N
NH S-K+
C2H5OH N
O R1-CONHNH2 N
HN
NO2 NO2 SH
O Ar
Ar = different aryl groups
N C Desai* & P N Shihora