Dual antagonists

RP and 71.7% ANN. The key descriptors for the RP model are 12 topological indices that include six E-state indices, i.e. SssCH2, SssO, SaasC, SdO, SsssN and SssssC. The classifier that combines topological indices and decision trees may be used for the virtual screening of DA, SA and Dual antagonists. 

Carceller E, Merlos M, Giral M, Balsa D, Almansa C, Bartroli J, Garcia-Rafanell J, Forn J. [(3-Pyridylalkyl)piperidylidene]-benzocycloheptapyridine derivatives as dual antagonists of PAF and histamine. /. Med. Chem., 1994, 37, 2697-2703. 

Piwinski JJ, Wc g JK, Green MJ, Ganguli AK, Billah MM, West Jf, RE, Kreutner W. Dual antagonists of platdet activating factor and histamine. J Med Chem 1991 34 457-461... 

Dual Antagonists Providing Two Separately Acting Drugs. . . 90... 

Several members of this dual antagonist series showed marked antitumor activities in experimental animals and in man. In both the pharmacologic and subsequent clinical studies, 72 and 73 (in which the aziridine ring carbons are unsubstituted methylene groups) were found to behave essentially like the typical ethylenimine-type alkylating agents (e.g., TEPA, or thio-TEPA). 

The dual antagonist approach is relatively new, but it has already produced several new anticancer agents which have been showing promise in the clinical trials. This, in itself, is sufficient reason for continuing on with the exploration of this approach, of its further possibilities, or limitations. 

TR-14035 (o4P1/oe4 P7 in-tegrin dual antagonist) CDCA-NBD (7-nitrobenz-2-oxa-1,3-diazole chenodeoxycholate)... 

Tsuda-Tsukimoto, M., Maeda, T., Iwanaga, T., Kume, T. and Tamai, I. (2006) Characterization of hepatobiliary transport systems of a novel alpha4betal / alpha4beta7 dual antagonist, TR-14035. Pharmaceutical Research, 23, 2646-2656. 

Piwinski, J. J., Wong, J. K., Green, M. J., Ganguly, A. K., Billah, M. M., West, R. E., Jr, Kreutner, W. Dual antagonists of platelet achvating factor and histamine. Identification of structural requirements for dual activity of N-acyl-4-(5,6-dihydro-ll//-benzo[5,6]cyclohepta-[l,2-h]pyridin-ll-ylene) piperidines. J. Med. Chem. 1991, 34, 457-461. 

Sato, I., Takizawa, S. et al. (2007) A dual antagonist for chemokine CCR3 receptor and histamine HI receptor. European Journal of Pharmacology, 563, 224-232. 

Struzik ZR, et al (2005) Dual Antagonistic Autonomic Control Necessary for 1/f... 

Caballero R, Valenzuela C, Longobardo M. Effects of rupatadine, a new dual antagonist of histamine and platelet-activating factor receptors, on human cardiac Kvl.5 channels. Br J Pharmacol 1999 128 1071-81. 

An interesting synthetic approach to 6-fluoro-3-(3-oxopiperazin-l-ylmethyl)-2-phenylquinolin-4-carboxyhc acid [(5)-l-cyclohexylethyl]amide 167-dual antagonist for NK2 and NK3 receptors - is presented in Scheme 72 [105], The reaction... 

All three compounds discussed in this section (i.e. 228-230) have reached Phase n clinical trials as agents for treatment Schizophrenia. Development of BMY-14802 (228) was discontinued more than 10 years ago. For ABT-925 (229), Phase II trials were terminated in 2011 for JNJ-37822681 (230), the latest clinical study was completed in February 2012 [113], Despite the disease addressed by 228-230 is common, the compounds express their effect through interactions with different biological targets. In particular, BMY-14802 (228) developed by Bristol-Myers Squibb acts as a dual antagonist of Oj and 5-HTia receptors. However, it should be... 

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