INTRODUCTION
In the recent advancement of targeted therapeutics that was coupled with new approaches in target identification have accelerated the need to design small compounds with drug like properties [1]. Quinoxaline is well known for its broad coverage in the field of medicine as well as for its application in the pharmaceuticals as they have shown wide range of biological properties such as antimicrobial [2], antibacterial [3], antitubercular [2, 4], antiprotozoal [5] , anti-candida [2, 6], anti-cancer [7], anti-AIDS [8] and anti-inflammatory [9] activities. Many scientists report quinoxalinone derivatives as non-classical analogues of the antifolic agents-methotrexate and trimetrexate, as well as the quinoxaline N-oxide with antibacterial …show more content…
Good absorption after oral administration was obligatory for analgesic use. Therefore, we analyzed these derivatives according to the rule-of-five developed by Lipinski et al., (Table 3). The rule-of-five theoretically characterizes molecular properties for orally active drugs. The rule states that the 90% of orally active drugs present number of hydrogen bond acceptors ≤ 10 and donors ≤ 5, clogP ≤ 5 and molecular weight (MW) ≤ 500. Molecules violating more than one of these rules may have problems with bioavailability. The results show that compounds DM1, DM2, and DM3 fulfill the Lipinski rule-of-five (Table 3). The rest of the compounds DM4, DM5 violated only the criterion of molecular weight.
Analgesic activity
The results of the analgesic activity indicate that all the synthesized compounds exhibited significant activity. At 60 min, when compared with standard drug pentazocine compound DM2, DM3 and DM5 showed good analgesic activity. The other compound DM1 and DM4 exhibited moderate analgesic activity at 60 min. The decreasing order of analgesic activity (at 60 min) of the synthesized compounds was found to be
In the recent advancement of targeted therapeutics that was coupled with new approaches in target identification have accelerated the need to design small compounds with drug like properties [1]. Quinoxaline is well known for its broad coverage in the field of medicine as well as for its application in the pharmaceuticals as they have shown wide range of biological properties such as antimicrobial [2], antibacterial [3], antitubercular [2, 4], antiprotozoal [5] , anti-candida [2, 6], anti-cancer [7], anti-AIDS [8] and anti-inflammatory [9] activities. Many scientists report quinoxalinone derivatives as non-classical analogues of the antifolic agents-methotrexate and trimetrexate, as well as the quinoxaline N-oxide with antibacterial …show more content…
Good absorption after oral administration was obligatory for analgesic use. Therefore, we analyzed these derivatives according to the rule-of-five developed by Lipinski et al., (Table 3). The rule-of-five theoretically characterizes molecular properties for orally active drugs. The rule states that the 90% of orally active drugs present number of hydrogen bond acceptors ≤ 10 and donors ≤ 5, clogP ≤ 5 and molecular weight (MW) ≤ 500. Molecules violating more than one of these rules may have problems with bioavailability. The results show that compounds DM1, DM2, and DM3 fulfill the Lipinski rule-of-five (Table 3). The rest of the compounds DM4, DM5 violated only the criterion of molecular weight.
Analgesic activity
The results of the analgesic activity indicate that all the synthesized compounds exhibited significant activity. At 60 min, when compared with standard drug pentazocine compound DM2, DM3 and DM5 showed good analgesic activity. The other compound DM1 and DM4 exhibited moderate analgesic activity at 60 min. The decreasing order of analgesic activity (at 60 min) of the synthesized compounds was found to be