Structure-Activity Relationship Study

For a structure-activity relationship study on 5//-pyrido[4,3-(j]indoles (y-carbolines), we needed both 1-unsubstituted 271 and 1-substituted methyl 2,3-dihydro-3-oxo-5//-pyrido[4,3-(j]indole-4-carboxylates 272 (Scheme 42). 

On the other hand, multimodality of biological activities of melatonin is well known. Therefore various derivatives are needed for carrying out its structure-activity relationship study. 1-Hydoxymelatonin (19) would be a suitable seed for developing yet unknown results. 

Kim CU, Lew W, Wilhams MA, Wu H, Zhang L, Chen X, Escarpe PA, Mendel DB, Laver WG, Stevens RC (1998) Structure-activity relationship studies of novel carbocyclic influenza neuraminidase inhibitors, J Med Chem 41 2451-2460 Kim CU, Chen X, Mendel DB (1999) Neuraminidase inhibitors as anti-influenza virus agents. Antiviral Chem Chemother 10 141-154... 

Liu XH, Yang ZF, Wang LS. Three-dimensional quantitative structure-activity relationship study for phenylsulfonyl carboxylates using CoMFA and CoMSI A. Chemosphere 2003 53 945-52. 

Mokrosz JL et al. (1995) Structure-activity relationship studies of CNS agents, XIX Quantitative analysis of the alkyl chain effects on the 5-HTlA and 5-HT2 receptor affinities of 4-alkyl-1-arylpiperazines and their analogs. Arch Pharm (Weinheim) 328(2) 143-148... 

Verma RP (2007) Cytotoxicity of Heterocyclic Compounds against Various Cancer Cells A Quantitative Structure-Activity Relationship Study. 9 53-86 Verma RP, see Hansch C (2007) 10 43-74 Viola G, see Gambari R (2007) 9 265-276 Voelter W, see Khan KM (2007) 7 325-346... 

Cytotoxicity of Heterocyclic Compounds against Various Cancer Cells A Quantitative Structure-Activity Relationship Study... 

Testa, B., Kier, L. B. The concept of molecular structure in structure-activity relationship studies and drug design. Med. Res. Rev. 1991, 11, 35 8. 

R., Khaledi, M. G. Quantitative structure-activity relationships studies with micellar electrokinetic chromatography. Influence of surfactant type and mixed micelles on estimation of hydrophobicity and bioavailability. J. Chromatogr. A 1996, 727, 323-335. 

Previous syntheses An example of this point can be recognized by examination of one known synthesis of thienobenzazepines (Scheme 6.1). This synthetic route involves a key palladinm-catalyzed cross-conpling of stannyl intermediate 3, prepared by method of Gronowitz et al., with 2-nitrobenzyl bromide. Acetal deprotection and reductive cyclization afforded the desired thienobenzazepine tricycle 4. In support of structure activity relationship studies, this intermediate was conveniently acylated with varions acyl chlorides to yield several biologically active componnds of structure type 5. While this synthetic approach does access intermediate 4 in relatively few synthetic transformations for stractnre activity relationship studies, this route is seemingly nnattractive for preparative scale requiring stoichiometric amounts of potentially toxic metals that are generally difficult to remove and present costly purification problems at the end of the synthesis. 

Cone, E.J. McQuinn, R.L. and Shannon, H.E. Structure-activity relationship study of phencyclidine derivatives in rats. J. Pharmacol Fxp Ther 228 147-153, 1984. 

Effects of Sesquiterpene Lactones on Seed Germination. Sesquiterpene lactones are common constituents of the Asteraceae but are also found in other angiosperm families and in certain liverworts (31,32). These highly bitter substances exhibit a wide spectrum of biological activities (J 3) which include cytotoxicity, anti-tumor, anti-microbial, insecticidal (34) and molluscicidal (35) properties. Furthermore, they are known causes for livestock poisoning and contact dermatitis in humans (33). Structure-activity relationship studies on sesquiterpene lactones have demonstrated that biological activity frequently depend on the presence of the cr... 

Schmid, D., Ecker, G., Kopp, S., Hitzler, M., Chiba, P., Structure-activity relationship studies of propafenone analogs based on P-glycoprotein ATPase activity measurements, Biochem. Pharmacol. 1999, 58, 1447-1456. 

Aleksic et al. [47] estimated the hydrophobicity of miconazole and other antimycotic drugs by a planar chromatographic method. The retention behavior of the drugs have been determined by TLC by using the binary mobile phases acetone-n-hexane, methanol toluene, and methyl ethyl ketone toluene containing different amounts of organic modifier. Hydrophobicity was established from the linear relationships between the solute RM values and the concentration of organic modifier. Calculated values of RMO and CO were considered for application in quantitative structure activity relationship studies of the antimycotics. 

Synthesis of Derivatives of Pateamine A and Structure Activity Relationship Studies... 

Quantitative Structure-Activity Relationship studies search for a relationship between the activity/toxicity of chemicals and the numerical representation of their structure and/or features. The overall task is not easy. For instance, several environmental properties are relatively easy to model, but some toxicity endpoints are quite difficult, because the toxicity is the result of many processes, involving different mechanisms. Toxicity data are also affected by experimental errors and their availability is limited because experiments are expensive. A 3D-QSAR model reflects the characteristics of... 

Zelezetsky I, Tossi A (2006) Alpha-helical antimicrobial peptides - using a sequence template to guide structure-activity relationship studies. BBA-Biomembranes 1758 1436-1449... 

Meyers MJ, Sun J, Carlson KE, Marriner A, Katznellenbogen BS, Katzenellenbogen JA (2001) Estrogen receptor-/ potency-selective ligands structure-activity relationship studies of diarylpropionitriles and their acetylene and polar analogues. J Med Chem 44 4230-4251... 

The discovery of BB-3497 was the result of screening a proprietary library for potential metalloenzyme inhibitors at the British Biotech Pharmaceutical Co. Ltd. [73]. This compound was originally prepared in a nonstereoselective manner and its stereochemistry was assigned on the basis of matrix metal-loprotease (MMP) inhibitory activity. The asymmetric synthesis of BB-3497 and the establishment of its stereochemistry by small-molecule X-ray crystallography was later reported by Pratt et al. [83]. Further structure-activity relationship studies of BB-3497 with respect to the modification of the P2 and P3 side chains [84] and metal binding group [85] were later reported by the scientists at British Biotech. These studies revealed that none of the... 

Smythies, J. R., and Sykes, E. A. (1966) Structure-activity relationship studies on mescaline The effect of dimethoxyphenylethylamine and N N-dimethyl mescaline on the conditioned avoidance response in rat. Psychopharmacologia, 8 324-330. 

The chemical diversity of pyrrolidine alkaloids indicates a broad spectrum of biological activities, which, however, does not allow, at the present time, structure-activity relationship studies. The available data are inhomogeneous, ranging from investigations of pure compounds to reports of use in folk medecine. 

Yoshida, K. and Niwa, T. (2006) Quantitative structure-activity relationship studies on inhibition of HERG potassium channels. Journal of Chemical Information and Modeling, 46, 1371-1378. 

Rastelli, G., Fanelli, F., Menziani, M.C., Cocchi, M. and De Benedetti, P.G. (1991) Conformational analysis, molecular modeling and quantitative structure-activity relationships studies of 2,4-diamino-6,7-dimethoxy-2-substituted quinazoline al-adrenergic antagonists. Journal of Molecular Structure (Theochem), 251, 307—318. 

The rate of acid-catalyzed degradation of the penicillins also depends largely on the nature of their acylamido side chain. Structure-activity-relationship studies undertaken for the rational design of orally active penicillins have shown that the stability in gastric juice increases with the sum of Taft s inductive substituent constants (of values) of the 6-amino side chain [95]. 

Byk G, Dubertret C, Escriou V, et al. Synthesis, activity, and structure-activity relationship studies of novel cationic lipids for DNA transfer. J Med Chem 1998 41(2) 229-235. 

Dequalinium salts can be purchased from Sigma Chemical Co., St. Louis, Missouri, U.S.A. Analogues of dequalinium, however, are not commercially available they can be synthesized according to protocols by Galanakis et al. (44 6). In a structure-activity relationship study (38), we found that the methyl group in ortho position to the quaternary nitrogen at the quinolinium ring system seems to play an essential role in the... 

Weissig V, Lizano C, Ganellin CR, Torchilin VP. DNA binding cationic bola-somes with delocalized charge center a structure-activity relationship study. STP Pharma Sci 2001 11 91-96. 

Structure-Activity Relationship Studies of the Antimicrobial Activities of the Host... 

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