Stereoselectivity and Affinity in Molecular Pharmacology

Miranda, J. F. Rodrigues de; Ariëns, E. J.

doi:10.1007/978-3-0348-7094-8_4

Cited by 31 publications

(23 citation statements)

References 69 publications

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“…Analysis of chirality-activity relationships found a useful mathematical basis when LEHMANN and colleagues (LEHMANN 1986(LEHMANN , 1987LEHMANN et al 1976) developed what they termed eudismic analysis. Briefly, they introduced the following definitions:…”

Section: Pfeiffer's Rule and Eudismic Analysismentioning

confidence: 97%

Chiral Recognition in Biochemical Pharmacology: An Overview

Testa¹,

Mayer²

2003

Stereochemical Aspects of Drug Action and Disposition

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Section: Pfeiffer's Rule and Eudismic Analysismentioning

confidence: 97%

Chiral Recognition in Biochemical Pharmacology: An Overview

Testa¹,

Mayer²

2003

Stereochemical Aspects of Drug Action and Disposition

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“…The polarizability, however, and the electron-donating properties of this particular double bond are diminished compared to a vinyl group [24]. This not only explains the low biological activity of compounds (12) and (13) but at the same time also enhances activity of the ether (8). Looking at Fig.5 it becomes evident that in this latter compound the polarizable lone pair of the oxygen accomodates itself easily into the plane of maximal mutual interaction because an sp3-hybridized side chain possesses all rotational degrees of freedom.…”

Section: Interaction With Oxygen and Surfur Groupsmentioning

confidence: 96%

“…Yet another class of parapheromones interesting in this context are oxa-multifidenes and thia-multifidenes such as compounds (8), (9), (12), (13) and (14). Though our primary aim at isosterical molecules mimicking the natural signal can Only the bonding electron pair of the -C = O double bond is directly accessible for mutual polarization and formation of 7~ complexes, because it alone is arranged in the same spatial plane as the electron cloud of the original double bond (compare Fig.4 and 5).…”

Section: Interaction With Oxygen and Surfur Groupsmentioning

confidence: 99%

Binding‐Mechanism and Sensitivity in Gamete Chemotaxis of the Phaeophyte Cutleria multifida

Boland

Terlinden

Jaenicke

et al. 1982

European Journal of Biochemistry

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Female gametes of the marine brown alga Cutleriu multificIa discharge multifidene into the water to attract the swimming males. The physicochemical principle of interaction between semiochemical and membrane receptor site is seen in mutual but complementary induced dipoles. Halogenated derivatives of multifidene with intact overall structure and stereochemistry but altered electronic properties were synthesized and assayed as lures. A direct correlation was observed between increasing polarizability and biological activity, thus proving the proposed mechanism. The low threshold concentration of this communication system (4 x lo9 molecules/ml), together with a detailed knowledge of the gamete's architecture, swimming velocity and stimulus response time, indicates that very few, may be even single, molecules are able to trigger the sensomotoric chain. The rigidity of the natural signal molecule was recognized as an important element in inducing conformational fitting in the ligand/receptor complex.Brown algae (Phaeophyceae) are a cosmopolitan class of the division Heterokontophyta. They have their habitat in the coastal zones of all continents and may grow on rocks, wharves or organic substrates. For reproduction they have evolved a great variety of mechanisms ranging from vegetative propagation to sexual reproduction, including combinations of both. In isogamous and anisogamous forms, flagelbated motile male and female gametes may be released from the respective gametangia. In many cases a secretion of a pheromone is observed after settlement of the female on a surface [ 1,2]. The recently examined subclasses Laminariales [ 3 ] and Desmarestiales [4] are oogamous and form semiochemicals which, in addition to attracting sperm, induce the release of sperm from the antheridia. Surprinsingly, such water-borne messengers are strongly hydrophobic: Unsaturated hydrocarbons without other functional groups are the only substances which have been characterized so far [5,6]. Many of them are alicyclic C1l-hydrocarbons with three double bonds, though other degrees of (un)saturation are also well established [7,8]. Cutleria multifidu, an inhabitant of Mediterranian coastal waters, during spring time releases male and female gametes. After settlement macrogametes secrete a bouquet of three closely related C11H16 substances into the surroundings : multifidene, (+)-(1) ; aucantene, (+)-(2); and ectocarpene, S-( +)-(3). Only the first of them has significant luring activity [9]. The fact that all three compounds belong to the same class of cyclo-olefinic hydrocarbons with similar physicochemical properties but only one of them is the hormone, indicates a very precise messenger/receptor interaction. Receptor studies with about 30 chemically modified 'multifidenes' as parapheromones revealed an unusually low threshold concentration for the natural semiochemical (6.5 pmol/l) and very exacting demands on size and shape [lo]. Partly hydrogenated derivatives of the pheromone underlined the particular importance of the double bonds as ...

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“…1 So, it is extremely necessary to study each stereoisomer separately. With the correct therapeutic information it is possible to maximize the properties of the drug by taking the most potent enantiomer, the eutomer, 2 or eliminating the enantiomer that may cause side effects, the distomer. The latter can be linked to a secondary molecular target.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of new 1,2,4-oxadiazoles carrying (1'S,2'S)-t-butyloxycarbonyl-1-amino-2- methyl-1-butyl and (1'S)-t-butyloxycarbonyl-1'-amino-1'-ethyl groups at C-5

Braga¹,

Melo²,

Srivastava³

et al. 2004

J. Braz. Chem. Soc.

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descrita. As estruturasedos intermediários e compostos finais foram determinadas a partir dos dados espectroscópicos. A facile and efficient synthesis of 3-aryl-5-[(1S)-t-butyloxycarbonyl-1-amino-(2S)-methyl-1-butyl)]-1,2,4-oxadiazoles 4a-f and 3-phenyl-5-[(1S)-t-butyloxycarbonyl-1-amino-1-ethyl]-1,2,4-oxadiazole 6 starting from arylamidoximes, N-t-Boc-L-isoleucine and N-t-Boc-L-alanine is decribed.The structures of the intermediates and final compounds have been deduced from spectroscopic data.

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Stereoselectivity and Affinity in Molecular Pharmacology

Cited by 31 publications

References 69 publications

Chiral Recognition in Biochemical Pharmacology: An Overview

Chiral Recognition in Biochemical Pharmacology: An Overview

Binding‐Mechanism and Sensitivity in Gamete Chemotaxis of the Phaeophyte Cutleria multifida

Synthesis of new 1,2,4-oxadiazoles carrying (1'S,2'S)-t-butyloxycarbonyl-1-amino-2- methyl-1-butyl and (1'S)-t-butyloxycarbonyl-1'-amino-1'-ethyl groups at C-5

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