Structure activity studies

Tutorial Selection of Relevant Descriptors in a Structure-Activity Study [19]... 

Carhart R E, D H Smith and R Venkataraghavan 1985. Atom Pairs as Molecular Features in Structure Activity Studies Definition and Applications. Journal of Chemical Information and Computer Scienc 25 64-73. 

Structure-activity studies of 5,6,7,8-tetrahdyro-5,5,8,8-tetramethyl-2-quinoxaline derivatives necessitated the preparation of thiophene-containing compound 17. Stetter conditions using thiazolium salt 20 as catalyst resulted in the preparation of 1,4-diketone 21 from 18 and 19. Condensation of 21 with phosphorus pentasulfide followed by saponification resulted in 17. In this fashion, the authors replaced the amide linker of parent compound 22 with the rigid thiophene moiety. 

Coleman et al. have performed a preliminary structure/activity study for a series of analogues of 77 [149]. They found that removal of the naphthoate moiety (88 Scheme 11.11) dramatically reduced the yield of DNA alkylation, while replacement of the NH2 group with O-benzyl (89 and 90) abolished DNA alkylation completely. Compound 91 alkylated DNA with reduced efficiency, so this effect is not simply due to a requirement for a hydrogen bond donor at this position. Perhaps the amide is required at this position to increase the ability of the C=0 to act as a hydrogen bond acceptor. Importantly, they found a strong correlation between the extent of in vitro DNA alkylation and cell culture cytotoxicity. 

Arg-2, Pro-3, Arg-4, Leu-5, Ser-6, Lys-8 Gly-9, Pro-10 and Met-11 into apelin-13 reduced [125I]-(Pyr1)apelin-13 binding to apelin receptors expressed in cell lines, suggesting they are important residues for receptor interaction. Structure activity studies using fragments of apelin-17 also identified Gln-1, Pro-12 and Phe-13 not essential for apelin binding. 

While none of these neutrophil receptors has yet been sequenced, partial purification of the formyl peptide receptors has been reported (16). The formyl peptide receptor is particularly attractive because of the extensive structure-activity studies on peptide ligands by Freer and coworkers (17,18). The receptor is a trans-membrane glycoprotein with apparent molecular weight of 60,000 based on proteolysis (19) and photoaffinity (20) labeling studies. 

Free SM Jr, Wilson JW. A mathematical contribution to structure-activity studies. J Med Chem 1964 7 395-9. 

Carhart RE, Smith DH, Venkataraghavan R. Atom pairs as molecular features in structure-activity studies definition and applications. I Chem Inf Comput Sci 1985 25 64-73. 

Topliss JG, Costello RJ. Chance correlations in structure-activity studies using multiple regression analysis. J Med Chem 1972 15 1066-9. 

BUTTERFIELD D A, MARINA A, JAROSLAW K, ANTONIO s (2002) FeruUc add antioxidant protection against hydroxyl and peroxyl radical oxidation in synaptosomal and neuronal cell culture systems in vitro Structure activity studies. JNutri Biochem, 13(5) 273-81. 

Moriguchi, I. Quantitative structure-activity studies I. Parameters relating to hydrophobicity. Chem. Pharm. Bull. 1975, 23, 1A7-1S7. 

Fujita, T Nishioka, T., Nakajima, M. Hydrogen-bonding parameter and its significance in quantitative structure-activity studies. /. Med. Chem. 1977, 20, 1071-1081. 

T. Fujita and T. Ban, Structure-activity study of phenethylamines as substrates of biosynthetic enzymes of sympathetic transmitters. J. Med. Chem., 14 (1971) 148-152. 

Thus, for structure-activity studies of MDMA-like substances, emphasis has been placed on the use of (-l-)-MBDB as the training drug, since it seems to possess a primary psychopharmacology similar to that of MDMA, but lacks the psychostimulant component of MDMA. That is, MBDB is pharmacologically less complex. 

Glennon, R.A. Young, R. and Flank, A.E. Structure-activity studies on methoxyaubstituted phenylisopropylamines using drug discrimination methodology. Pharmacol Biochem Behav 22 723-729. 1985. 

Structure activity studies on compound (1), focusing on optimization at the 2-position of the quinoline and at the capping group, resulted in the... 

Since the modular structure of (13a) is easily amenable to parallel synthesis, extensive structure-activity studies were carried out with this compound. This generated not only a large body of structure-activity data, but also led to a remarkable optimization of the metabolic and pharmacokinetic properties of (13a). 

When assayed in HEK293 cells transfected with the cloned human, rat and guinea pig TRPVl, (23a) showed similar potencies. Not unexpeetedly, (23a) showed poor metabolic stability and a structure-activity study to optimize potency and drug-like properties was initiated. Modification on the left-handed A -aryl section showed that ... 

Much remains to be accomplished in the separation, isolation, and identification of both naturally occurring and synthetic bioactive materials effective in the germination of parasitic weed seeds. Structure-activity studies suffer from the lack of separation of isomers in most synthetic samples. Strigol is an important tool in basic studies on the effect of chemicals on seed germination, but it is highly unlikely that the compound will meet practical field... 

Diana GD, Oglesby RC, Akullian V, et al. Structure-activity studies of 5-[[4-(4,4-dihydro-2-oxazolyl)phenoxy]alkyl]-3-methylisoxazoles inhibitors of picornavirus uncoating. J Med Chem 1987 30 383-388. 

Diana GD, Cutcliffe D, Oglesby RC, Otto MJ, Mallamo JP, Akullian V, McKinlay MA. Synthesis and structure-activity studies of some disubsti-tuted phenylisoxazoles against human picornavirus. J Med Chem 1989 32 450-455. 

Scherrer, R. A., The treatment of ionizable compounds in quantitative structure-activity studies with special consideration of ion partitioning, in Magee, P. S. Kohn, G. K. Menn, J. J. (eds.), Pesticide Syntheses through Rational Approaches, ACS Symposium Series 225, ACS (American Chemical Society), Washington, DC, 1984, pp. 225-246. 

Structure-activity studies in the phenylacetic acid antiinflammatory series have shown that inclusion of a methyl group on the benzylic carbon usually leads to maximal activity. It is of note that this... 

Recent structure-activity studies of 1-alkylbenzo[a]pyrenes also suggest that DNA intercalation of benzo[a]pyrene (BP) metabolites plays a role in the mechanism of BP carcinogenesis (38). The addition of bulky alkyl groups at the 1-position of BP, which inhibit DNA intercalation of 1-alkyl-BP metabolites (19), causes a reduction in carcinogenic activity. 

Structure-Activity Studies and the Design of Synthetic Superoxide Dismutase (SOD) Mimetics as Therapeutics... 

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