Sulfamylurea Hypoglycemic Agents. III. Tetrasubstituted Sulfamylureas and N-Sulfamylcarbamates

Jw, McFarland; Cf, Gerber; Wm, McLamore

doi:10.1021/jm00330a011

Cited by 7 publications

(1 citation statement)

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“…The series was admir ably evaluated by the investigators with efforts made to correlate physical with biological properties. Among factors influencing activity were particle surface area which controlled rates of solution and, thus, oral absorption, and increase in acidity which increases resistance to metabolism and thus dura tion of action (222,223). Since the compounds have a high lipid: water parti tion ratio, small changes in lipophilicity had no significant effect on activity.…”

Section: Oxotremorine Arecolinementioning

confidence: 99%

Some Relationships Between Chemical Structure and Pharmacological Activities

Cavallito¹

1968

Annu. Rev. Pharmacol.

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Earlier reviews in this series dealt with some relationships of chemical structure with biological activities (1-3) i the present assignment is restricted essentially to pharmacologically active compounds. As with the earlier re views, the published literature is not covered exhaustively, but some new re ports and observations are included which appeared from about September, 1964 [termination of coverage of last review (1)] to May, 1967. Where useful for purposes of relationship, selected older literature is cited.Over the years attempts have been made to devise general hypotheses pertaining to structure-activity relationships (SAR) and drug mechanisms of action. Recent efforts include variations of receptor occupancy hypotheses (Ariens, Stephenson), rate or kinetic hypotheses (Paton), and more chemi cally descriptive concepts (Belleau and others). In reviewing publications of the past two years that could be considered pertinent to SAR, one is im pressed by the gulf that exists between most synthesizers of new molecules and the developers of general hypotheses. For example, from 310 complete articles published in J. Med. Chern. (1965-66), only six made reference to these hypotheses either as stimuli for the project or as vehicles for cor relating SAR. This might indicate that the hypotheses are sterile or inade quate for either predictive or correlative purposes or that there is little in terest or inclination among most investigators in relating specific observa tions to general hypotheses. Most of these hypothes,t!s have indeed offered little that is of substantive value from a chemical perspective of devising novel molecules of biological interest. However, the efforts are commendable and some of these hypotheses may evolve and develop into theories with use ful correlative and predictive values. As hypotheses become more chemically descriptive, one can anticipate that there will be a greater consideration of such hypotheses by the designers of new, biologically interesting molecules.Their more recent concepts have been summarized by Ariens (4) and Paton (5). Shortcomings of the Ariens and Stephenson receptor occupancy and the Paton rate hypotheses have been analyzed by Belleau (6) as back ground for discussion of his "conformational perturbation" hypothesis.Bloom & Goldman (7) further consider these and modify and extend some of Belleau's views in proposing a "dynamic receptor hypothesis" relevant to catecholamine-adenine mononucleotide interactions in adrenergic mech anisms. These reviews are recommended to the cautious reader; space does 39 Annu. Rev. Pharmacol. 1968.8:39-66. Downloaded from www.annualreviews.org Access provided by New York University -Bobst Library on 05/14/15. For personal use only.Quick links to online content Further ANNUAL REVIEWS

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Section: Oxotremorine Arecolinementioning

confidence: 99%