SYNTHESIS AND ANTIMICROBIAL EVALUATION OF 2-(4-FLUORO BENZYLTHIO)-N-(SUBSTITUTED PHENYL)PYRIMIDINE-4-AMINES
HTML Full TextSYNTHESIS AND ANTIMICROBIAL EVALUATION OF 2-(4-FLUORO BENZYLTHIO)-N-(SUBSTITUTED PHENYL)PYRIMIDINE-4-AMINES
N.M. Goudgaon*, Y. Rohini Reddy and B.U. Sheshikant
Department of Post Graduate Studies and Research in Chemistry, Gulbarga University, Gulbarga - 585106, Karnataka, India
ABSTRACT: Reaction of 4-fluorobenzylchloride with 2-thiouracil (1) gave 2-(4-fluorobenzylthio)pyrimidin-4(3H)-one (2), which on chlorination with POCl3 furnished 4-chloro-2-(4-fluorobenzylthio)-4-chloropyrimidine (3). This intermediate when treated with various substituted anilines gave desired targeted compounds 4(a-k) in 50-90% yield. Structural assignments of the synthesized compounds were based on their IR, 1H NMR, Mass and analytical data. The antimicrobial evaluation of newly synthesized compounds was carried out by cup-plate method. The investigation of antimicrobial screening reveals that the compounds 4b, 4g, 4c and 4f showed good activity against bacterial strain B. subtilis. Compounds4a, 4e, 4b, 4c, 4f, 4g and 4h wereactive against bacterial strain P. aeruginosa. Compounds 4a and 4c were active against fungul strain A. niger. Compounds 4e, 4b and 4j showed good activity against fungal strain A. flavus. All the synthesized compounds showed excellent antifungal activity against T.viridae. Remaining compounds exhibited moderate to poor activity against bacterial and fungal strains when compared to standard drugs Gentamycin and Fluconazole respectively. So, further we have carried out the antifungal screening of all the synthesized compounds at different concentrations against T. viridae to determine their IC50 values. Compounds 4e, 4b, 4g, 4i, 4d, 4f and 4j have shown better IC50 values
Keywords: |
Pyrimidines, Anilines, Antibacterial activity, Antifungal activity
INTRODUCTION:Pyrimidines have a long and distinguished history extending from the days of their discovery as important constituents of nucleic acids to their current use in medicinal chemistry. Pyrimidine derivatives are well known to exhibit various biological and pharmacological activities such as antitumour 1, anti-HIV 2, 3, antimicrobial4-6, antidepressants 7, hypnotics and sedatives 8, analgesicand anti-inflammatory 9, antioxidant 10 and acid-pump antagonist 11 activities
The presence of fluorine increases thermal stability, lipophilicity and bioavailability 12. Although the utility of fluorine substituents is there, only few methods are available for carbon-fluorine bond formation 13-14, which indicates the unavailability of suitable fluorination methods.
As incorporating fluorine into system is not easy, we have reacted different fluorine substituted reagents with 2-thiouracil derivatives so as to get pyrimidine molecule bearing fluorine on its substituent. In view of potent pharmacological activity associated with pyrimidines and enhancement of activity by introducing fluorine in the molecule, We herein report the synthesis and antimicrobial activities of 2-(4-fluorobenzylthio)-N-(substituted phenyl)pyrimidine-4-amines (Scheme 1).
MATERIALS AND METHODS: All the solvents and chemicals were obtained from S. D. Fine-Chem Ltd. Mumbai and were purified by standard procedures. Melting points were determined in open capillary and were uncorrected. IR spectra in KBr disc were recorded on Perkin-Elmer-Spectrum-one FT-IR spectrophotometer (νmax in cm-1). 1H NMR spectra were recorded in DMSO-d6 with a BRUKER NMR 500 MHz Spectrophoto-meter using TMS as internal standard (chemical shift in δ or ppm). Mass spectra were recorded on LCMS 2010A, SHIMADZU Mass Spectrophoto-meter.
Purity of the compounds was checked by TLC using silica gel ‘G’ plates obtained from Whatman Inc, and a fluorescent indicator.
RESULT AND DISCUSSION: Reaction of 2-thiouracil (1) with 4-flourobenzylchloride in aq. NaOH gave compound 2 in 85% yield having m.p. 158-160˚C (Scheme 1). 1H NMR spectra displayed a singlet at δ 4.39 due to two protons of CH2 and two doublet peaks, one at δ 7.24 due to C5H of pyrimidine and another at δ 7.39 due to C6H of pyrimidine ring and multiplet from δ 7.25-7.90 due to four aromatic protons confirms the formation of compound 2.
SCHEME 1
Further formation of compound 2 is confirmed by the presence of absorption bands at 1708, 1574cm-1 assigned to C=O, C=N with 687 cm-1 characterized by C-F stretching were shown in its IR spectrum. Chlorination of compound 2 with POCl3 yielded 4-chloro-2-(4-fluorobenzylthio)pyrimidine (3) in 90% yield, m.p. 44-46˚C. Formation of this compound 3 was confirmed by the presence of absorption peaks at 1575, 736 and 707 cm-1 due to C=N, C-Cl and C-F in its IR spectrum.
Further confirmation of compound 3 is by the presence of singlet at δ 4.4 due to two protons of SCH2PhF, aromatic protons signal as a multiplet at δ 7.14 -7.16, characteristic absorption of C5Hand C6H of pyrimidine ring as a doublet at δ 7.40 and δ 8.60 respectively in its 1H NMR spectrum. This intermediate on reaction with various aromatic amines in presence of piperidine in methanol furnished the desired targeted compounds (4a-k) in 50 - 80% yield. Compound 4a was obtained in 50% yield having m.p. 104˚-106˚C. The IR (cm-1) spectrum of compound 4a showed absorptions at 3081, 1575 and 707 cm-1 due to the presence of aromatic NH, C=N and C-F groups.
1H NMR displayed singlet at δ 4.34 due to two protons of SCH2PhF, multiplet in the region δ 6.77-7.40 due to eight aromatic protons and a singlet at δ 6.42 due to NH proton and two doublet peaks at δ 6.20 and δ 8.18 due to C5H and C6H of pyrimidine ring.
Final confirmation of compound 4a is by the appearance of molecular ion peak at m/z = 330 (M+1, 100%) in its mass spectrum. Physical data of all the synthesized compounds are tabulated in Table 1.
TABLE 1: PHYSICAL DATA OF SYNTHESIZED COMPOUNDS (2, 3 & 4a-k)
R | Molecular formula | M. P (ºC) | Yield (%) | Elemental Analysis Calc, (Found) (%) | |||
C | H | N | |||||
2 | -- | C11H9 FN2OS | 158-160 ºC | 85 | 51.76(51.70) | 3.55(3.50) | 10.97(10.91) |
3 | -- | C11H8N2ClFS | 44-46 ºC | 90 | 53.33(53.28) | 3.25(3.20) | 11.31(11.28) |
4a | 2-F | C17H13N3F2S | 103-106 ºC | 50 | 61.99(61.95) | 3.97(3.93) | 12.75(12.71) |
4b | 4-Br,3-CF3 | C18H12N3BrF4S | 195-198 ºC | 62 | 47.18(47.14) | 2.63(2.59) | 9.17(9.13) |
4c | 4-F | C17H13N3F2S | 102-104 ºC | 65 | 61.99(61.95) | 3.97(3.93) | 12.75(12.71) |
4d | 4-Cl | C17H13N3ClFS | 99-100 ºC | 80 | 59.10(59.06) | 3.78(3.73) | 12.15(12.11) |
4e | 4-OCH3 | C18H16N3OFS | 118-120 ºC | 70 | 63.32(63.25) | 4.72(4.67) | 12.31(12.28) |
4f | 3-F | C17H13N3F2S | 135-138 ºC | 62 | 61.99(61.95) | 3.98(3.94) | 12.76(12.70) |
4g | H | C17H14N3FS | 114-116 ºC | 72 | 65.57(65.53) | 4.53(4.49) | 13.49(13.45) |
4h | 2-NO2 | C17H13N4O2FS | 95-98 ºC | 66 | 57.29(57.25) | 3.68(3.64) | 15.72(15.68) |
4i | 3-NO2 | C17H13N4O2FS | 118-120 ºC | 62 | 57.29(57.25) | 3.68(3.64) | 15.72(15.68) |
4j | 4-NO2 | C17H13N4O2FS | 91-92 ºC | 60 | 57.29(57.25) | 3.68(3.64) | 15.72(15.68) |
4k | 2-F,4-I | C17H12N3IF2S | 102-104 ºC | 67 | 44.85(44.80) | 2.65(2.61) | 9.23(9.19) |
EXPERIMENTAL:
Synthesis of 2-(4-fluorobenzylthio)pyrimidine-4(3H)-one (2): 2-Thiouracil (1) (0.075 mole) and NaOH (0.1 mole) were dissolved in hot water (450 ml) and then mixed with 4-fluorobenzylchloride (0.1 mole). The temperature was increased until all the 4-fluorobenzylchloride went into the solution for about one hour. On cooling the separated solid product was collected by filtration, washed with water, dried and crystallized from ethanol to afford compound 2.
Yield: 85%. M.P: 158-160 oC. IR(cm-1): 1708 (C=O), 1574 (C=N), 687 (C-F). 1H NMR (DMSO-d6): δ4.39 (s, 2H, SCH2 PhF), 7.24 (d, 1H, C5H of pyrimidine), 7.25-7.90 (m, 4H, ArH), 7.39 (d, 1H, C6H of pyrimidine). Anal. Calcd. for C11H9FN2OS: C, 51.76; H, 3.55; N, 10.97. Found: C, 51.72; H, 3.51; N, 10.92%.
Synthesis of 2-(4-fluorobenzylthio)-4-chloro pyrimidine (3): A mixture of 2-(4-fluorobenzylthio)pyrimidine-4(3H)-one (2) (0.01 mole) and POCl3 (0.1 mole) was refluxed for 3 hours. Excess of POCl3 was removed under reduced pressure and the reaction mixture was treated with ice/water. The separated solid was extracted with ether (3 x 100 ml) and the ether extract was washed with 5% aq.NaHCO3 solution (1 x 25 ml), water (1 x 25 ml) and then dried over anhydrous sodium sulphate and after solvent evaporation yielded the crude compound 3 was recrystallized from EtOH.
Yield: 90%. M.P: 44-46 oC. IR(cm-1): 1575 (C=N), 707 (C-F), 736 (C-Cl). 1H NMR (DMSO-d6): δ 4.4 (s, 2H, CH2),7.14-7.16 (m, 4H, ArH ), 7.40 (d, 1H, C5H of pyrimidine), 8.6 (d, 1H, C6H of pyrimidine). Anal. Calcd. for C11H8N2ClFS: C, 53.33; H, 3.25; N,11.31. Found: C, 53.28; H, 3.21; N, 11.27%.
Synthesis of 2-(4-fluorobenzylthio)-N-(substituted phenyl)pyrimidine-4-amines (4a-k): To a solution of 2-(4-fluorobenzylthio)-4-chloropyrimidine(3) (0.001 mole) in methanol (20 ml) and catalytic amount of piperidine, appropriate aromatic primary amine (0.001 mole) was added and refluxed for 12-15 hours on water bath. Concentrated the reaction mixture under reduced pressure and the residue triturated with little crushed ice and neutralized the aqueous layer with 0.1N HCl. Solid separated was filtered, washed with cold water and recrystallized from ethanol to yield the target compounds (4a-k).
Spectral data of compounds (4a-k):
2-(4-Fluorobenzylthio)-N-(2-fluorophenyl) pyrimidine-4-amine (4a): Yield: 50%. M.P: 103-106ºC. IR (cm-1): 3081 (NH), 1575 (C=N), 707 (C-F). 1H NMR (DMSO-d6): δ 4.34 (s, 2H, SCH2PhF), 6.77-7.40 (m, 8H, ArH ), 6.42 (s, 1H, NH), 6.20 (d, 1H, C5H of pyrimidine), 8.18 (d, 1H, C6H of pyrimidine). Mass: m/z = 330 (M+1, 100%). Anal. Calcd. for C17H13N3F2S: C, 61.99; H, 3.97; N, 12.75. Found: C, 61.95; H, 3.93; N, 12.71%.
2-(4-Fluorobenzylthio)-N-(4-bromo-3-trifluoro methylphenyl)pyrimidin-4-amine (4b): Yield: 62%. M.P: 195-198ºC. IR (cm-1): 3078 (NH), 1624 (C=N), 697 (C-F). 1H NMR (DMSO-d6): δ 4.418 (s, 2H, SCH2PhF), 7.23-7.83 (m,7H, ArH), 8.23 (d, 1H, C6H of pyrimidine), 8.377 (s, 1H ,NH), 6.70 (d, 1H, C5H of pyrimidine). Mass: m/z= 455 (M+2, 100%). Anal. Calcd. for C18H12N3BrF4S: C, 47.18; H, 2.63; N, 9.17. Found: C, 47.14; H, 2.59; N, 9.13%.
2-(4-Fluorobenzylthio)-N-(4-fluorophenyl) pyrimidine-4-amine (4c): Yield: 65%. M.P: 102-104ºC. IR (cm-1): 3076 (NH),1601 (C=N), 697 (C-F). 1H NMR (DMSO-d6): δ 4.30 (s, 2H, SCH2PhF), 6.51(d, 1H, C5H of pyrimidine), 7.20-7.40(m, 9H, 8ArH & NH), 7.96 (d, 1H, C6H of pyrimidine). Mass: m/z = 330 (M+1, 100%). Anal. Calcd. for C17H13N3F2S: C, 61.99; H, 3.97; N, 12.75. Found: C, 61.95; H, 3.93; N, 12.71%.
2-(4-Fluorobenzylthio)-N-(4-chlorophenyl) pyrimidine-4-amine (4d): Yield: 80%. M.P: 99-100ºC. IR(cm-1): 3076 (NH), 1601(C=N), 697 (C-F), 733 (C-Cl). 1H NMR (DMSO-d6): δ 4.32 (s, 2H, SCH2PhF), 6.94-7.40 (m,8H, ArH), 7.26 (s, 1H, NH), 6.17 (d, 1H, C5H of pyrimidine), 7.90 (d, 1H, C6H of pyrimidine). Mass: m/z = 347 (M+2, 100%). Anal. Calcd. for C17H13N3ClFS: C, 59.10; H, 3.78; N, 12.15. Found: C, 59.06; H, 3.73; N, 12.11%.
2-(4-Fluorobenzylthio)-N-(4-methoxyphenyl) pyrimidin-4-amine (4e): Yield: 70%. M.P: 118-120ºC. IR(cm-1): 3076 (NH), 1601 (C=N), 697 (C-F). 1H NMR (DMSO-d6): δ 3.61 (s, 3H, OCH3), 4.34 (s, 2H, SCH2PhF), 6.96-7.41(m, 8H, ArH), 6.19 (d, 1H, C5H of pyrimidine), 7.28 (s, 1H, NH ), 7.98 (d, 1H, C6H of pyrimidine). Mass: m/z = 342 (100%). Anal. Calcd. for C18H16N3OFS: C, 63.32; H, 4.72; N, 12.31. Found: C, 63.25; H, 4.67; N, 12.28%.
2-(4-Fluorobenzylthio)-N-(3-fluorophenyl) pyrimidine-4-amine (4f):Yield: 62%. M.P: 135-138ºC.IR(cm-1): 3286 (NH), 1628 (C=N), 696 (C-F). 1H NMR (DMSO-d6): δ 4.34 (s, 2H, SCH2PhF), 6.19 (d, 1H, C5H of pyrimidine), 6.96-7.41 (m, 8H, ArH), 7.28 (s, 1H, NH), 7.98 (d, 1H, C6H of pyrimidine). Mass: m/z = 328(M+1, 100%). Anal. Calcd. for C17H13N3F2S: C, 61.99; H, 3.98; N, 12.76. Found: C, 61.95; H, 3.94; N, 12.70%.
2-(4-Fluorobenzylthio)-N-(phenyl)pyrimidine-4-amine (4g): Yield: 72%. M.P: 114-116ºC. 1H NMR (DMSO-d6): δ 4.31 (s, 2H, SCH2PhF), 6.17 (d, 1H, C5H of pyrimidine), 6.94-7.39 (m, 9H, ArH), 7.26 (s, 1H, NH), 7.96 (d, 1H, C6H of pyrimidine). Mass: m/z = 312 (100%). Anal. Calcd. for C17H14N3FS: C, 65.57; H, 4.53; N, 13.49. Found: C, 67.53; H, 4.49; N, 13.45%.
2-(4-Fluorobenzylthio)-N-(2-nitrophenyl) pyrimidine-4-amine (4h): Yield: 66%. M.P: 95-98ºC. 1H NMR (DMSO-d6): δ 4.36 (s, 2H, SCH2PhF), 6.17 (d, 1H, C5H of pyrimidine), 7.22-7.43 (m, 9H, 8ArH & NH), 7.97 (d, 1H, C6H of pyrimidine). Mass: m/z = 356 (100%). Anal. Calcd. for C17H13N4O2FS: C, 57.29; H, 3.68; N, 15.72. Found: C, 57.25; H, 3.64; N, 15.68%.
2-(4-Fluorobenzylthio)-N-(3-nitrophenyl) pyrimidine-4-amine (4i): Yield: 62%. M.P: 118-120ºC.1H NMR (DMSO-d6): δ 4.33 (s, 2H, SCH2PhF), 6.19 (d, 1H, C5H of pyrimidine), 7.23-7.45 (m, 9H, 8ArH & NH), 11.33 (s, 1H, NH), 7.99 (d, 1H, C6H of pyrimidine). Mass: m/z = 356 (100%). Anal. Calcd. for C17H13N4O2FS: C, 57.29; H, 3.68; N, 15.72. Found: C, 57.25; H, 3.64; N, 15.68%.
2-(4-Fluorobenzylthio)-N-(4-nitrophenyl) pyrimidine-4-amine (4j):Yield: 60%. M.P: 91-92ºC.1H NMR (DMSO-d6): δ 4.38 (s, 2H, SCH2PhF), 6.93 (d, 1H, C5H of pyrimidine), 7.26-7.85 (m, 9H, 8ArH & NH), 8.15 (d, 1H, C6H of pyrimidine). Mass: m/z = 356 (100%). Anal. Calcd. for C17H13N4O2FS: C, 57.29; H, 3.68; N, 15.72. Found: C, 57.25; H, 3.64; N, 15.68%.
2-(4-Fluorobenzylthio)-N-(2-fluoro-4-iodo phenyl)pyrimidine-4-amine (4k):Yield: 67%. M.P: 102-104ºC. IR (cm-1): 3073 (NH), 1578 (C=N), 695 (C-F). 1H NMR (DMSO-d6): δ 4.34 (s, 2H, SCH2PhF), 6.19 (d, 1H, C5H of pyrimidine), 6.96-7.41 (m, 8H, 7ArH & NH), 7.98 (d, 1H, C6H of pyrimidine). Mass: m/z = 456 (M+1, 100%). Anal. Calcd. for C17H12N3IF2S: C, 44.85; H, 2.65; N, 9.23. Found: C, 44.80; H, 2.61; N, 9.19%.
Antimicrobial Activity: The antimicrobial activities were performed by cup plate method 15. The sample was dissolved in DMF at the concentration of 1000 µg/ml. Antibacterial activity was carried out against two gram +ve S. aureus, B. subtilis and two gram -ve P. aeruginosa and E. coli bacterial strains.
Antifungal activity was carried out against A. niger and A. flavus and T. viridae under aseptic conditions. Gentamycin and Fluconazole were used as standard drug for antibacterial and antifungal activities respectively.
The zone of inhibition was compared with standard drug after 24 hours of incubation at 25°C for antibacterial activity and 48 hours at 30°C for antifungal activity. The investigation of anti-microbial screening reveals that the compounds 4b, 4g, 4c and 4f showed good activity against bacterial strain B. subtilis. Compounds4a, 4e, 4b, 4c, 4f, 4g and 4h were active against bacterial strain P. aeruginosa. Compounds4a and 4c were active against fungul strain A. niger.
Compounds 4e, 4b and 4j showed good activity against fungal strain A. flavus. All the synthesized compounds showed excellent antifungal activity against T. viridae. Remaining compounds exhibited moderate to poor activity against bacterial and fungal strains when compared to standard drug. Results are tabulated in Table 2.
Further the antifungal screening of all the synthesized compounds at different concentrations 1000, 750, 500, and 250 µg/ml to determine the IC50 (50% inhibition concentration) values against T. viridae.
Compounds 4e, 4b, 4g, 4i, 4d, 4f and 4j have exhibited better IC50 values. IC50 is defined as the drug concentration that produces 50% of the maximal effect. The values are tabulated in Table 3 and percentages of inhibition are shown graphically in Figure 1.
TABLE 2: ANTIMICROBIAL ACTIVITY OF SYNTHESIZED COMPOUNDS (4a-k)
Compound | Doseµg/ml | Zone of inhibition in mm | ||||||
E. coli | B. substilis | S. aureus | P. aeruginosa | A.niger | A. flavus | T. viridae | ||
4a | 1000 | -- | 15 | 09 | 15 | 20 | 15 | 18 |
4b | 1000 | 14 | 26 | 14 | 14 | 08 | 16 | 22 |
4c | 1000 | -- | 24 | 08 | 14 | 18 | 15 | 20 |
4d | 1000 | 26 | 18 | 11 | 10 | -- | 15 | 21 |
4e | 1000 | 22 | 17 | 14 | 15 | 10 | 18 | 23 |
4f | 1000 | 25 | 22 | 14 | 14 | 08 | -- | 24 |
4g | 1000 | 20 | 25 | 14 | 14 | 10 | 13 | 25 |
4h | 1000 | 24 | 20 | 13 | 13 | 05 | 12 | 24 |
4i | 1000 | 20 | 18 | 14 | 12 | 14 | 15 | 21 |
4j | 1000 | 18 | 17 | 10 | 11 | 08 | 16 | 21 |
4k | 1000 | 20 | 22 | 12 | 10 | 12 | 13 | 15 |
Gentamycin | 1000 | 33 | 30 | 18 | 16 | -- | -- | -- |
Fluconazole | 1000 | -- | -- | -- | -- | 20 | 20 | 23 |
TABLE 3: IC50 VALUES OF SYNTHESIZED COMPOUNDS (4a-k)
Compound No. | Zone of Inhibition in mm against fungal strainTrichoderma viridae | ||||
Dose1000 µg/ml | Dose750 µg/ml | Dose500 µg/ml | Dose250 µg/ml | IC50µg/ml | |
4a | 17.7 | 20 | 20.3 | 17.3 | 149.8 |
4b | 22 | 20 | 19.3 | 12.3 | 224.4 |
4c | 20.3 | 20 | 16.7 | 17 | 147.9 |
4d | 21 | 17.3 | 19 | 14.7 | 178.9 |
4e | 23.7 | 19.3 | 18 | 12 | 247.1 |
4f | 24.3 | 19.3 | 18.3 | 17.3 | 178.9 |
4g | 25.7 | 20.3 | 19.7 | 16.3 | 197.5 |
4h | 24 | 20.7 | 20 | 18 | 166.5 |
4i | 21 | 21 | 20 | 14 | 189.2 |
4j | 21 | 22.7 | 20.3 | 16 | 178.9 |
4k | 20.3 | 20 | 16.3 | 17 | 147.5 |
Fluconazole | 23.3 | 20.7 | 18.7 | 17 | 172 |
FIGURE 1: GRAPH SHOWING % INHIBITION AT DIFFERENT CONCENTRATIONS
CONCLUSION: The present work reports the synthesis and antimicrobial activities of 2-(4-Fluorobenzylthio)-N-(substituted phenyl) pyrimidine-4-amines. Among the synthesized compounds 4b, 4g, 4c and 4f showed good activity against bacterial strain B. subtilis. Compounds4a, 4e, 4b, 4c, 4f, 4g and 4h wereactive against bacterial strain P. aeruginosa. Compounds4a and 4c were active against fungul strain A. niger. Compounds 4e, 4b and 4j showed good activity against fungal strain A. flavus. All the synthesized compounds showed excellent antifungal activity against T. viridae. Remaining compounds exhibited moderate to poor activity against bacterial and fungal strains when compared to standard drug.
So, further we have carried out the antifungal screening of all the synthesized compounds at different concentrations against T. viridae to determine their IC50 values. Compounds 4e, 4b, 4g, 4i, 4d, 4f and 4j have shown better IC50 value. Further preclinical studies of the most potent compound are warranted.
ACKNOWLEDGEMENT: The authors are thankful to SAIF IIT-Madras for providing spectral data. The authors also thank Professor and Chairman, Department of Microbiology, Gulbarga University, Gulbarga for providing bacterial and fungal strains.
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How to cite this article:
Goudgaon NM, Reddy YR and Sheshikant BU: Synthesis and antimicrobial evaluation of 2-(4-fluorobenzylthio)-n-(substituted phenyl)pyrimidine-4-amines. Int J Pharm Sci Res 2013; 4(11): 4336-42. doi: 10.13040/IJPSR. 0975-8232.4(11).4336-42
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IJPSR
N.M. Goudgaon*, Y. Rohini Reddy and B.U. Sheshikant
Department of Post Graduate Studies and Research in Chemistry, Gulbarga University, Gulbarga - 585106, Karnataka, India
naganna_g@yahoo.com
20 June, 2013
15 July, 2013
26 October, 2013
http://dx.doi.org/10.13040/IJPSR.0975-8232.4(11).4336-42
01 November, 2013