- The cubane paradigm in bioactive molecule discovery: Further scope, limitations and the cyclooctatetraene complement
-
The cubane phenyl ring bioisostere paradigm was further explored in an extensive study covering a wide range of pharmaceutical and agrochemical templates, which included antibiotics (cefaclor, penicillin G) and antihistamine (diphenhydramine), a smooth muscle relaxant (alverine), an anaesthetic (ketamine), an agrochemical instecticide (triflumuron), an antiparasitic (benznidazole) and an anticancer agent (tamibarotene). This investigation highlights the scope and limitations of incorporating cubane into bioactive molecule discovery, both in terms of synthetic compatibility and physical property matching. Cubane maintained bioisosterism in the case of the Chagas disease antiparasitic benznidazole, although it was less active in the case of the anticancer agent (tamibarotenne). Application of the cyclooctatetraene (COT) (bio)motif complement was found to optimize benznidazole relative to the benzene parent, and augmented anticancer activity relative to the cubane analogue in the case of tamibarotene. Like all bioisosteres, scaffolds and biomotifs, however, there are limitations (e.g. synthetic implementation), and these have been specifically highlighted herein using failed examples. A summary of all templates prepared to date by our group that were biologically evaluated strongly supports the concept that cubane is a valuable tool in bioactive molecule discovery and COT is a viable complement.
- Houston, Sevan D.,Fahrenhorst-Jones, Tyler,Xing, Hui,Chalmers, Benjamin A.,Sykes, Melissa L.,Stok, Jeanette E.,Farfan Soto, Clementina,Burns, Jed M.,Bernhardt, Paul V.,De Voss, James J.,Boyle, Glen M.,Smith, Maree T.,Tsanaktsidis, John,Savage, G. Paul,Avery, Vicky M.,Williams, Craig M.
-
supporting information
p. 6790 - 6798
(2019/07/22)
-
- ANTICANCER AGENT DELIVERY MOLECULE
-
PROBLEM TO BE SOLVED: To provide a compound which can be used as an anticancer agent targeting a cancer cell that highly expresses Lysine-specific demethylase 1 (LSD1) or salt thereof. SOLUTION: The present invention provides a compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof, where Ar, R1, R2, L, Z, p, q, *1 and *2 are as defined in the specifications. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT
- -
-
Paragraph 0183-0184; 0186
(2017/08/04)
-
- Retinobenzoic Acids. 6. Retinoid Antagonists with a Heterocyclic Ring
-
Several candidate retinoid anatgonists were designed on the basis of the ligand superfamily concept and synthesized.Retinoidal activities of these benzimidazole and benzodiazepine derivatives were examined by assay of differentiation-inducing activity on
- Eyrolles, Laurence,Kagechika, Hiroyuki,Kawachi, Emiko,Fukasawa, Hiroshi,Iijima, Tohru,et al.
-
p. 1508 - 1517
(2007/10/02)
-
- Method for preparing benzoic acid derivatives
-
This invention relates to a synthesis method favorable for the industrial production of a benzoic acid derivative having a retinoid activity of the general formula: STR1 wherein the derivative can be obtained by a simple procedure in safety with high yield.Specifically, this invention relates to a synthesis method characterized in that only one vessel is needed for several reactions in the different steps of subjecting acetanilide as a starting material, which is readily available and safe to handle, to Friedel-Crafts reaction with 2,5-dimethyl-2,5-dichlorohexane; subjecting the thus obtained compound to acyl exchange reaction with monomethyl ester terephthalic chloride, followed by hydrolysis; and recrystallizing from a mixture of methanol and water.Moreover, the crystals in novel form obtained by the synthesis method of this invention are suitable for formulation, because the amount of solvents remaining therein after recrystallization is small and the grain size thereof is uniform.
- -
-
-
