- Synthesis and structure-activity relationships of A novel class of dithiocarbamic acid esters as anticancer agent
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Based on a novel lead compound 4-methylpiperazine-1-carbodithioic acid 3-cyano-3,3-diphenylpropyl ester 1, the systematic structural modification was carried out. All the synthesized compounds were evaluated for their in-vitro anticancer activities on four to six different cell lines at three different concentrations. Most of the tested compounds could selectively inhibit the growth of HL-60 and Bel-7402 cell lines at a medium concentration. Four compounds (3f, 3g, 3n, and 5) were selected for the IC50 test, and the results revealed that three compounds (3g, 3n, and 5) showed almost the same or a slightly weaker activity than compound 1 against HL-60, and three compounds (3f, 3g, and 3n) showed >2-fold higher potency than compound 1 against Bel-7402. The in-vivo efficacy of 3n · HCl was evaluated with transplanted hepatocyte carcinoma 22 as an in-vivo test model. It was found that 3n · HCl could inhibit significantly the growth of tumor, and that this effect was dose-dependent. Meanwhile, the compound 3n · HCl showed low toxicity compared with compound 1 · HCl as evidenced by the little body-weight loss. These results confirmed that compound 3n · HCl is more potent than the lead compound 1 · HCl. Preliminary structure-activity relationships indicated that: a) Both nitrile group and the cyclic amine containing at least two nitrogens were indispensable moieties to keep the activity; b) substitution of the piperazine ring is unfavorable for the improvement of activity; c) the suitable linker joining the piperazinyl dithiocarboxyl and diphenylacetonitril group should be ethylene; d) a non-coplanar arrangement of the two benzene rings appears to be essential for activity. Based on a novel lead compound 4-methyl-piperazine-1-carbodithioic acid 3-cyano-3,3-diphenyl-propyl ester 1, the systematic structural modification was carried out. Compounds 3g and 3n were found to show more potent biological activities than lead compound 1. Some useful SARs were revealed Copyright
- Hou, Xueling,Ge, Zemei,Wang, Tingmin,Guo, Wei,Wu, Jun,Cui, Jingrong,Lai, Chingsan,Li, Runtao
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scheme or table
p. 320 - 332
(2011/11/05)
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- Design, synthesis and antimuscarinic activity of some imidazolium derivatives
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A series of imidazolium salt derivatives was prepared as part of a search for subtype-selective antimuscarinic agents. On the basis of measurements of the antimuscarinic activity and subtype-selectivity for M2 and M3 muscarinic receptors, the structure-activity relationships of these compounds are discussed.
- Miyachi, Hiroyuki,Kiyota, Hiromi,Segawa, Mitsuru
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p. 3003 - 3008
(2007/10/03)
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- Muscarinic receptor antagonists
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Compounds of the formula I STR1 wherein X, Y and v are as defined below, novel intermediates used in their synthesis, and the pharmaceutically acceptable salts of such compounds and intermediates. The compounds of formula I and the novel intermediates used in their synthesis are muscarinic receptor antagonists that are selected for smooth muscle muscarinic sites and are useful in the prevention and treatment of diseases associated with altered motility or tone of smooth muscle, such as irritable bowel syndrome, diverticular disease, urinary incontinence, aesophageal achalasia, and chronic obstructive airways disease.
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- Muscarinic receptor antagonists
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A compound of the formula (IA) or (IB), useful in treating diseases associated with the altered motility and/or tone of smooth muscle, such as irritable bowel syndrome, of the formula:- and their pharmaceutically-acceptable salts, where Y is-CH?CH?-,-CH=CH-,-CH?-S-,-CH?-O-,-O-or-S-; and X is a group of the formula:- wherein m is 1 or 2; R1 and R2 are each independently H or C?-C? alkyl or together represent-(CH?)n-where n is an integer of from 2 to 5; R3 is H or C?-C? alkyl; Z is a direct link,-CH?-,-(CH? )?-,-CH?O-or-CH?S-; and R? is pyridyl, pyrazinyl, thienyl or a group of the formula:- where either R? and R? are each independently selected from H, C?-C? alkyl, C?-C? alkoxy, halo,-CF?,-CN,-(CH?) pNR? R?,-OCO(C?-C? alkyl),-CO(C?-C? alkyl),-CH(OH)(C?-C? alkyl),-C(OH) (C?-C? alkyl)?,-SO?NH?,-NHSO?(C?-C? alkyl),-(CH?)pOH,-(CH?)p COO(C?-C? alkyl),-(CH?)pCONR? R?, or R? and R? together represent-(CH?)q-,-O(CH?) rO-or-O(CH? )t-where in the latter the oxygen atom is attached to the 3-or 4-position of the benzene ring; R? and R? are each independently H or C?-C? alkyl; p is 0, 1 or 2; q is 3, 4 or 5; r is 1, 2 or 3; and t is 2, 3 or 4.
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