Synthesis and Characterization of Steroid‐linked N‐(2‐Chloroethyl)nitrosoureas

Abstract

Syntheses of steroid-linked N-[N'-(2-chloroethyl)-N'-nitrosocarbamoyl]-(CNC-) amino acid esters and -amides with potential antineoplastic activity are described. The esters are prepared by reaction of CNC-amino acids with steroids using N,N'-carbonyldiimidazole and N,N'-dicyclohexylcarbodiimide. The corresponding amides are prepared by reaction of 1-(CNC-amino acyloxy)-pyrrolidine-2,5-diones with 17 beta-amino-3-hydroxy-1,3,5(10)-estratriene or 17 beta-O-[4-(6-aminohexylamino)-1,4-dioxo-butyl]-estradiol. Estradiol-17 beta-hemisuccinate is esterified with N-(2-hydroxyethyl)-N'-(2-chloro-ethyl)-N'-nitrosourea (HECNU). Spectroscopic characteristics and relative binding affinities to steroid receptors are given.

New and efficient routes to CpRe(CO)3 substituted steroids

“…This result confirms that a bulky substitution at C-6 induces a dramatic decrease in the affinity of the modified hormone for the ER. [12][13][14] In conclusion, the results presented illustrate a new route to CpRe(CO) 3 substituted steroids. They show that (i) the introduction of the metal carbonyl unit on a steroid in the last step of the synthesis is possible [for this purpose, fulvenes are more interesting than the corresponding cyclopentadienes because of the great number of products accessible according to the conditions (basic versus nucleophilic) used] and (ii) BrRe(CO) 5 is a suitable precursor for the elaboration of CpRe(CO) 3 units in organic solvents.…”

Design, Synthesis, and Initial Biological Evaluation of a Steroidal Anti-Estrogen–Doxorubicin Bioconjugate for Targeting Estrogen Receptor-Positive Breast Cancer Cells

“…In the field of hormone-responsive breast cancer, this approach typically involved linking a potent estrogen receptor targeting agent to a second component, such as an antimetabolite, intercalating agent, antimitotic, alkylating agent, or metal chelating group. − In the case of estrogen receptor-targeted hybrids, these efforts have been almost invariably unsuccessful. To a significant extent, the lack of success can be traced to an over-reliance on chemical transformations of readily available estrogens or easily modified sites on those estrogens to prepare the target compounds.…”

Convergent synthesis of a steroidal antiestrogen-mitomycin C hybrid using “click” chemistry

“…In the field of hormone responsive breast cancer, this strategy typically involves linking a potent estrogen receptor (ER) targeting agent to a second component, such as an anti-metabolite, intercalating agent, anti-mitotic, alkylating agent or metal chelating group. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Unfortunately, the resultant products from these efforts proved almost invariably to be less effective at each of its targets than the separate, individual components. Typically one observes loss of ER affinity, absence of cancer cell selectivity, and reduction in cytotoxicity associated with the therapeutic moiety.…”