212914-87-9Relevant articles and documents
BIFUNCTIONAL COMPOUNDS
-
Page/Page column 51; 85; 86, (2021/05/07)
The invention provides a bifunctional compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein said Targeting Ligand, Linker and Degron are as described herein.
A Series of Enthalpically Optimized Docetaxel Analogues Exhibiting Enhanced Antitumor Activity and Water Solubility
Ma, Yun-Tao,Yang, Yanting,Cai, Pei,Sun, De-Yang,Sánchez-Murcia, Pedro A.,Zhang, Xiao-Ying,Jia, Wen-Qiang,Lei, Lei,Guo, Mengqi,Gago, Federico,Wang, Hongbo,Fang, Wei-Shuo
supporting information, p. 524 - 533 (2018/03/30)
A dual-purpose strategy aimed at enhancing the binding affinity for microtubules and improving the water solubility of docetaxel led to the design and synthesis of a series of C-2- and C-3′-modified analogues. Both aims were realized when the C-3′ phenyl group present in docetaxel was replaced with a propargyl alcohol. The resulting compound, 3f, was able to overcome drug resistance in cultured P-gp-overexpressing tumor cells and showed greater activity than docetaxel against drug-resistant A2780/AD ovarian cancer xenografts in mice. In addition, the considerably lower hydrophobicity of 3f relative to both docetaxel and paclitaxel led to better aqueous solubility. A molecular model of tubulin-bound 3f revealed novel hydrogen-bonding interactions between the propargyl alcohol and the polar environment provided by the side chains of Ser236, Glu27, and Arg320.
From libraries to candidate: The discovery of new ultra long-acting dibasic β2-adrenoceptor agonists
Alcaraz, Lilian,Bailey, Andrew,Cadogan, Elaine,Connolly, Stephen,Jewell, Robert,Jordan, Stephen,Kindon, Nicholas,Lister, Andrew,Lawson, Mandy,Mullen, Alexander,Dainty, Ian,Nicholls, David,Paine, Stuart,Pairaudeau, Garry,Stocks, Michael J.,Thorne, Phillip,Young, Alan
, p. 689 - 695 (2012/03/26)
Libraries of dibasic compounds designed around the molecular scaffold of the DA2/β2 dual agonist sibenadet (Viozan) have yielded a number of promising starting points that have been further optimised into novel potent and selective target molecules with required pharmacokinetic properties. From a shortlist, 31 was discovered as a novel, high potency, and highly efficacious β2-agonist with high selectivity and a duration of action commensurable with once daily dosing.
