Synthesis and antiulcer activity of N-substituted N'-[3-[3-(piperidinomethyl)phenoxy]propyl]ureas: histamine H2-receptor antagonists with potent mucosal protective activity

Abstract

As an aim toward developing new antiulcer agents, new N-substituted N'-[3-[3-(piperidinomethyl)phenoxy]propyl]ureas were synthesized and evaluated for histamine H2-receptor antagonistic, gastric antisecretory, and gastric mucosal protective activities. A QSAR study showed that the most favorable N-substituents were electron-donating straight-chain alkyl groups of short length such as ethyl group from the viewpoint of dual action, i.e., gastric antisecretory and mucosal protective actions. Among the ureas studied, compounds 4, 5, and 8-10 were selected as candidates for further study.

A Scaleable Synthesis of BAY 43-9006: A Potent Raf Kinase Inhibitor for the Treatment of Cancer

“…Reaction of 9 with isocyanate 10 in methylene chloride 11 generated clean urea 3 ( BAY 43 - 9006 ) in 92% yield (Scheme ). Target 3 was synthesized in similar yield (91%) by coupling aniline 11 with 9 in the presence of N , N ‘-carbonyldiimidazole (CDI) without formation of symmetrical byproducts. Earlier experiences with this reaction, as well as others, indicated that concentration was the key to minimizing, or totally eliminating, the production of symmetrical ureas.…”

Synthesis and evaluation of sulfonyl-substituted ruthenium complex as potential antibacterial activity againstStaphylococcus aureus

“…18 A large number of drugs containing sulfonyl groups have been successfully used in clinical practice. For example, the non-steroidal anti -inflammatory drug celecoxib, 19 the treatment of benign prostatic hyperplasia drug tamsulosin, 20 the treatment of male erectile dysfunction drugs sildenafil, 21 antiarrhythmic drugs Dofetilide, 22 antimicrobial drug sulfadiazine, 23 diuretic drug torasemide, 24 long-acting antidiabetic drug glimepiride, 25 treatment of acute myeloid leukemia drug amsacrine, 26 antihypertensive drug methyclothiazide, 27 the gout drug probenecid, 28 the anti -ulcer drug famotidine, 29 and the antiemetic drug Sulpiride. 30 However, currently, ruthenium complex antimicrobial agents containing sulfonyl groups have not been approved for clinical application.…”

Application of Sulfonyl in Drug Design

“…易代谢位点而提高药物代谢稳定性, 延长其作用时间, 提高其生物利用度, 从而改善小分子的药代动力学性 质; 磺酰基的引入可以增加小分子的极性从而降低 hERG 毒性. 临床应用的含磺酰基代表药物有非甾体抗 炎药塞来昔布(Celecoxib, 1) [1] 、治疗良性前列腺增生药 物坦索罗辛(Tamsulosin, 2) [2] 、治疗男性勃起功能障碍药 物西地那非(Sildenafil, 3) [3] 、抗心律失常药多菲利特 (Dofetilide, 4) [4] 、抗菌药物磺胺嘧啶(Sulfadiazine, 5) [5] 、 利尿药托拉塞米(Torasemide, 6) [6] 、 长效抗糖尿病药物格 列美脲(Glimepiride, 7) [7] 、 治疗急性骨髓性白血病药物安 吖 啶 (Amsacrine, 8) [8] 、 抗 高 血 压 药 物 甲 氯 噻 嗪 (Methyclothiazide, 9) [9] 、治痛风药物丙磺舒(Probenecid, 10) [10] 、抗溃疡药物法莫替丁(Famotidine, 11) [11] 、止吐药 舒必利(Sulpiride, 12) [12] 等(图 1).…”