Hardcastle, Ian R.’s team published research in Journal of Medicinal Chemistry in 1995-01-20 | CAS: 622-86-6

Journal of Medicinal Chemistry published new progress about Antiestrogens Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 622-86-6 belongs to class ethers-buliding-blocks, name is (2-Chloroethoxy)benzene, and the molecular formula is C8H9ClO, HPLC of Formula: 622-86-6.

Hardcastle, Ian R. published the artcileRationally designed analogs of tamoxifen with improved calmodulin antagonism, HPLC of Formula: 622-86-6, the main research area is tamoxifen analog preparation calmodulin antagonism structure; antiestrogen tamoxifen analog calmodulin antagonism structure; breast tumor inhibition tamoxifen analog structure.

Computerized mol. modeling studies on the interactions of the antiestrogen tamoxifen and its analogs bound to the calcium-binding protein calmodulin have guided the rational design of more potent antagonists. Compounds with either three or four methylene units in the basic side chain or slim lipophilic 4-substituents were expected to be more potent. All compounds were tested for antagonism of the calmodulin-dependent activity of cAMP phosphodiesterase and for binding affinity to the estrogen receptor from rat uteri. Some compounds were assayed for cytotoxicity against MCF-7 breast tumor cells in vitro. Introduction of lipophilic 4-substituents was accomplished by using palladium(0)-catalyzed coupling reactions with a 4-iodinated precursor. Both the 4-ethynyl and 4-Bu compounds were more potent calmodulin antagonists than tamoxifen. Extension of the basic aminoethoxy side chain of 4-iodotamoxifen and idoxifene ((E)-1-[4-[2-(N-pyrrolidino)ethoxy]phenyl]-1-(4-iodophenyl)-2-phenyl-1-butene) by one or two methylene units resulted in modest gains in calmodulin antagonism. All the compounds assayed retained estrogen receptor-binding characteristics. The compound possessing the optimal combination of calmodulin antagonism and estrogen receptor binding was (E)-1-[4-[3-(N-pyrrolidino)propoxy]phenyl]-1-(4-iodophenyl)-2-phenyl-1-butene (IC50 = 1.1 μM, receptor binding affinity = 23). Correlation between calmodulin antagonism and cytotoxicity was demonstrated for selected compounds

Journal of Medicinal Chemistry published new progress about Antiestrogens Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 622-86-6 belongs to class ethers-buliding-blocks, name is (2-Chloroethoxy)benzene, and the molecular formula is C8H9ClO, HPLC of Formula: 622-86-6.

Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem