99216-67-8Relevant articles and documents
Modifications of flexible nonyl chain and nucleobase head group of (+)-erythro-9-(2′s-hydroxy-3′s-nonyl)adenine [(+)-EHNA] as adenosine deaminase inhibitors
Kandalkar, Sachin R.,Ramaiah, Parimi Atchuta,Joshi, Manoj,Wavhal, Atul,Waman, Yogesh,Raje, Amol A.,Tambe, Ashwini,Ansari, Shariq,De, Siddhartha,Palle, Venkata P.,Mookhtiar, Kasim A.,Deshpande, Anil M.,Barawkar, Dinesh A.
, p. 5799 - 5819 (2017/09/28)
A series of terminal nonyl chain and nucleobase modified analogues of (+)-EHNA (III) were synthesized and evaluated for their ability to inhibit adenosine deaminase (ADA). The constrained carbon analogues of (+)-EHNA, 7a-7h, 10a-c, 12, 13, 14 and 17a-c appeared very potent with Ki values in the low nanomolar range. Thio-analogues of (+)-EHNA 24a-e wherein 5′C of nonyl chain replaced by sulfur atom found to be less potent compared to (+)-EHNA. Docking of the representative compounds into the active site of ADA was performed to understand structure-activity relationships. Compounds 7a (Ki: 1.1 nM) 7b (Ki: 5.2 nM) and 26a (Ki: 5.9 nM) showed suitable balance of potency, microsomal stability and demonstrated better pharmacokinetic properties as compared to (+)-EHNA and therefore may have therapeutic potential for various inflammatory diseases, hypertension and cancer.
IMIDAZO[1,2-b]PYRIDAZINE DERIVATIVES AS KINASE INHIBITORS
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Paragraph 0275; 0288; 0289, (2016/03/13)
The present invention is intended to provide a compound or a pharmacologically acceptable salt thereof which is useful in the treatment of a tumor through its ROS1 kinase enzyme activity inhibitory effect and NTRK kinase enzyme inhibitory effect. The present invention provides a compound having an imidazo[1,2-b]pyridazine structure represented by the general formula (I) or a pharmacologically acceptable salt thereof, and a pharmaceutical composition comprising the compound. In the formula, R1, G, T, Y1, Y2, Y3, and Y4 are as defined herein.
Structural requirements for the antiproliferative activity of pre-mRNA splicing inhibitor FR901464
Osman, Sami,Albert, Brian J.,Wang, Yanping,Li, Miaosheng,Czaicki, Nancy L.,Koide, Kazunori
supporting information; experimental part, p. 895 - 904 (2011/03/20)
FR901464, a natural product isolated from a bacterium source, activates a reporter gene, inhibits pre-mRNA splicing, and shows antitumor activity. We previously reported the development of a more potent analogue, meayamycin, through the total synthesis of