875110-16-0Relevant articles and documents
NOVEL CYCLOHEXANE DERIVATIVE, PRODRUG THEREOF AND SALT THEREOF, AND THERAPEUTIC AGENT CONTAINING THE SAME FOR DIABETES
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Page/Page column 59, (2008/06/13)
A cyclohexane derivative having the function of reducing a blood sugar level and having preferable properties required of medicines, such as long-lasting drug activity, metabolic stability, and safety; and a medicinal composition for use in the prevention or treatment of diseases attributable to hyperglycemia, such as diabetes, e.g., insulin dependent diabetes mellitus (type 1 diabetes) or noninsulin-dependent diabetes mellitus (type 2 diabetes), complications of diabetes, and obesity. The derivative is a compound represented by the formula (I): (wherein A is -O-, -CH2-, or -NH-; n is an integer selected between 0 and 1; R6 and R7 each independently is hydrogen or C1-6 alkyl; m is an integer selected among 1-3; Q is selected among the following formulae Q1 to Q5; Ar1 is optionally substituted arylene or optionally substituted heteroarylene, provided that the heteroarylene may be bonded to an aromatic carbocycle or aromatic heterocycle to form a fused ring; and Ar2 is optionally substituted aryl or optionally substituted heteroaryl), a prodrug of the compound, or a pharmaceutically acceptable salt of either. Also provided are a medicine, a medicinal composition, or the like each containing the compound.
Potential Antitumor Agents. 61. Structure-Activity Relationships for in Vivo Colon 38 Activity among Disubstituted 9-Oxo-9H-xanthene-4-acetic Acids
Rewcastle, Gordon W.,Atwell, Graham J.,Zhuang, Li,Baguley, Bruce C.,Denny, William A.
, p. 217 - 222 (2007/10/02)
Analogues of 9-oxo-9H-xanthene-4-acetic acid (XAA) bearing small, lipophilic 5-substituents are among the most dose-potent compounds yet reported with the capability of causing hemorrhagic necrosis of implanted colon 38 tumors in mice.To further extend structure-activity relationships among this class of compound, a series of XAA derivatives bearing two small lipophilic groups at various positions have been prepared and evaluated.The 5,6-disubstituted compounds in particular show consistently high levels of both dose potency and activity, suggesting this is the optimal configuration among substituted 9-oxo-9H-xanthene-4-acetic acids.The 5,6-dimethyl and 5-methyl-6-methoxy are the most effective analogues, showing in vivo colon 38 activity comparable to that of FAA at 10-15-fold lower doses and superior activity to FAA at the respective optimal doses, and the former has been selected for detailed evaluation.
Potential Antitumor Agents. 58. Synthesis and Structure-Activity Relationships of Substituted Xanthenone-4-acetic Acids Active against the Colon 38 Tumor in Vivo
Rewcastle, Gordon W.,Atwell, Graham J.,Baguley, Bruce C.,Calveley, Stephen B.,Denny, William A.
, p. 793 - 799 (2007/10/02)
In a search for compounds related to flavoneacetic acid with activity against solid tumors, a series of methyl- methoxy-, chloro, nitro-, and hydroxy-substituted xanthenone-4-acetic acids have been synthesized and evaluated against subcutaneously implanted colon adenocarcinoma 38 in vivo, using a short-term histology assay as a primary screening system.A major goal of this work was to identify compounds with similar profiles of activity to that of flavoneacetic acid but of higher potency.The level of activity of the compounds appeared to depend more on the nature of the substituent than its positioning, in the order Cl > Me, OMe > NO2, OH.However, the potency of the compounds was related much more to the position rather than the nature of the substitution, with 5-substituted compounds being clearly the most dose potent. 5-Methylxanthenone-4-acetic acid has a similar level of activity to that of flavoneacetic acid in the test systems employed but is more than 7-fold as does potent.
