Synthesis and Pharmacological Investigation of 3‐Subsituted‐amino‐2‐methylsulfanyl‐5,6,7,8‐tetrahydro‐3H‐benzo[4,5]thieno[2,3‐d]pyrimidin‐4‐ones as Analgesic and Anti‐Inflammatory Agents

Abstract

In the present work, design, synthesis, and pharmacological evaluation of the analgesic, anti-inflammatory, and ulcerogenic-index activities of new 3-subsituted-amino-2-methylsulfanyl-5,6,7,8-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-ones, structurally planed by exploiting a clear concept of bio-isosterism, are reported. All compounds exhibited significant analgesic and anti-inflammatory activity. Compounds A1, A3 showed higher analgesic activity and more potent anti-inflammatory activity than that of the reference compound diclofenac sodium. Interestingly, the test compounds showed only mild ulcerogenic potential when compared to that of acetylsalicylic acid.

2‐Aminothiophene derivatives as a new class of positive allosteric modulators of glucagon‐like peptide 1 receptor

“…The mixture was heated to dissolution in 15 ml DMSO at 70°C for 5 min, followed the addition of 20 ml of 50% EtOH/H 2 O at 70°C over 1–2 min and slow cooling to room temperature. The resulting slurry was filtered under vacuum, washed with water (2 × 5 ml), and the resulting white solid dried at 65°C (1 torr) overnite to afford 1.134 g (63.5%) of S‐2 ( 5 ) as a white powder: (Alagarsamy et al, 2007) MP >220°C (sublimation); IR (neat) 3658.11, 3279.65, 3231.38, 2979.41, 2970.73, 2887.97, 2658.12, 1644.23, 1599.54, 1537.52, 1488.96, 1472.93, 1462.00, 1453.49, 1435.17, 1391.95, 1383.41, 1356.01, 1328.42, 1266.33, 1239.95, 1149.53, 1089.42, 1031.83, 966.85, 946.82, 903.26, 883.08, 870.46, 811.04, 786.61, 762.26, 695.62, 665.48, 652.07, 626.73, 559.37, 526.18, 511.57, 489.72, 474.01, 452.92, 444.67, 435.80, 427.56 cm −1 ; 1 H NMR (hydrate form, 400 MHz, DMSO‐d 6 ) δ 1.03 (d, J = 6.44 Hz, 3H), 1.38 (m, 1H), 1.81 (m, 2H), 2.23 (dd, J = 10.0, 7.4 Hz, 1H), 2.62 (m, 2H), 3.06 (dd, J = 13.0, 4.0 Hz, 1H), 5.74 (s, 1H), 6.38 (s, 1H), 7.03 (s, 1H); 13 C NMR (100 MHz, DMSO‐d 6 ) δ 21.51 (q), 24.13 (t), 28.10 (d), 30.86 (t), 33.55 (t), 113.98 (s), 124.88 (s), 129.62 (s), 154.45 (s), 159.50 (s), 167.87 (s). MS (ESI) calculated for C 11 H 13 N 3 OS 2 267.1, found 266.2 [M − H] + , found 268.1 [M + H] + .…”

Design, Synthesis, Molecular Docking of some New Polyhydrobenzothieno- thiazolopyrimidinedione Glycoside Derivatives with Double Anti-microbial-Anti-inflammatory Action.

“…Theinopyrimidines are well known with its high pharmaceutical applications [30][31][32][33]. It was important to discover and develop new non selective antiinflammatory drugs (NSAIDs) due to the undesirable side effects of marketed anti-inflammatory drugs [34,35].Thus many literatures represented the roles of theinopyrimidinone derivatives as anti-inflammatory agents [36][37][38][39]. The compound N4-(3-(dimethylamino)propyl)-N2-methyl-6-(4-morpholinophenyl-)thieno [3,2-d] pyrimi-dine-2,4-diamine which is theinopyrimidinone derivative (V) was found to have antimalarial potential [40,41],while the other compound,…”

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“…Bioisosterism is a useful strategy for the lead optimization process and molecular modification for rational drug design [9]. The bioisostere concept is an over simplification of the role of scaffold's for activity, unless it plays a pivotal role for function or interaction such as for β-lactams in penicillins [9].…”

“…The bioisostere concept is an over simplification of the role of scaffold's for activity, unless it plays a pivotal role for function or interaction such as for β-lactams in penicillins [9]. On the basis of these results and in continuation of our project directed towards the design and synthesis of biologically active isosteric heterocyclic lead compounds [10][11][12][13], we summarize that replacement of CH by N of the phenyl ring in the antibacterials [14] 3,4-dihydrobenzo [4,5] imidazo[1,2-a]triazine A and the dihydroimidazole derivatives B, could give their biological isosteres 2-6 and 7-11 respectively ( Figure 1), with more potent antibacterial and antifungal activity.…”