15342-09-3Relevant articles and documents
Thiol-Containing Androgens as Suicide Substrates of Aromatase
Bednarski, Patrick J.,Porubek, David J.,Nelson, Sidney D.
, p. 775 - 779 (1985)
The thiol-containing androgens 17β-hydroxy-10β-mercaptoestr-4-en-3-one (1) and 19-mercaptoandrost-4-ene-3,17-dione (2) were synthesized and tested in human placental microsomes for their ability to suicide inhibit aromatase.Both compounds showed time-dependent, pseudo-first-order rates of inactivation of aromatase with Ki's of 106 and 34 nM and kcat's of 3.2E-3 and 1.2E-3 s-1 respectively for 1 and 2 at 30 deg C.Diffusion dialysis failed to reactivate aromatase previously inactivated by either compound, and both compounds required that NaDPH and O2 be present for time -dependent inactivation of the enzyme.The presence of the substrate, androst-4-ene-3,17-dione (5.0 μM), protected the enzyme from inactivation while cysteine (1.0 mM) failed to protect aromatase from inactivation by either compound.The above evidence demonstrates that both compounds are potent suicide inhibitors of aromatase.
Influence of catalyst on the formation of 5(10)- ene ketals from estra- 4-en-3-ones
Negi, Arvind S.,Kaushal, Amita,Rastogi, Reema,Ray, Suprabhat
, p. 2197 - 2201 (2007/10/03)
The effect of catalyst on formation of isomeric ketals from 19- nortestosterone and 19-nor-ethisterone is reported. Regioselectivity has been achieved with metal hydrides as catalyst, reported for the first time, to give 5(10)-ene ketals.
Synthesis of C-6 fluoroandrogens: Evaluation of ligands for tumor receptor imaging
Choe, Yearn Seong,Katzenellenbogen, John A.
, p. 414 - 422 (2007/10/02)
Seven androgens, substituted with fluorine at C-6, were prepared as potential imaging agents for androgen receptor-positive prostate tumors and were evaluated in vitro in terms of their lipophilicity and their relative binding affinities (RBA, relative to R1881 = 100) for the androgen receptor and for sex steroid binding protein.Introduction of a fluorine atom into the C-6 position of an androgen generally decreases binding affinity to the androgen receptor, except in the two cases: 6α-fluoro-19-nor-testosterone RBA = 41.6 versus 30.6 for the unsubstituted steroid) and 6α-fluorotestosterone (RBA = 8.9 versus 6.6).Receptor binding of the C-6 fluoro-androgens is also stereospecific, showing higher binding affinities for the α-epimers compared to the corresponding β-epimers (4:1 - 15:1).Binding affinity to sex steroid binding protein is the lowest with 19-nor-testosterone, which is also the least lipophilic androgen studied.Based on the binding properties of compounds in this series, 6α-fluoro-19-nor-testosterone appears to have the most promise as a tumor imaging agent. - Keywords: C-6-fluoroandrogens; fluorine substitution; relative binding affinity; 6α- and 6β-epimers; log Po/w; prostate tumors
Fluorine-18-Labeled Progestin Ketals: Synthesis and Target Tissue Uptake Selectivity of Potential Imaging Agents for Receptor-Positive Breast Tumors
Kochanny, Monica J.,VanBrocklin, Henry F.,Kym, Philip R.,Carlson, Kathryn E.,O'Neil, James P.,et al.
, p. 1120 - 1127 (2007/10/02)
We have studied two new fluorine-substituted progestins as potential imaging agents for progesterone-receptor-positive human breast tumors. The steroids are 16α,17α-fluoroacetophenone ketals of 16α,17α-dihydroxyprogesterone and 16α,17α,21-trihydroxy-19-norprogesterone. Synthesis of the latter compound in seven steps from 19-norandrost-4-ene-3,17-dione is reported. Both compounds demonstrate high affinity for the progesterone receptor (PgR) (52.5 and 240percent, respectively, relative to R5020 = 100). The syntheses were adapted to 18F-labeling with 4'--fluoroacetophenone, prepared from 4'-nitroacetophenone by nucleophilic substitution with K18F/Kryptofix. Considerable adjustment of reaction conditions was required to effect ketalization using tracer quantities of the ketone. In tissue distribution studies in estrogen-primed immature female rats, both ketals showed selective uterine uptake, which was blocked by coinjection of a saturating dose of the unlabeled progestin ORG 2058. Additionally, metabolic stability of the radiolabel was indicated by the low radioactivity levels seen in bone. Both compounds showed relatively high uptake in fat, in accord with their relative lipophilicities demonstrated by HPLC-derived octanol-water partition coefficients. The selective uterine uptake and metabolic stability of these compounds suggests that this class of PgR ligands might be promising for the selective imaging of receptor-positive tumors if derivatives of reduced lipophilicity can be prepared.
Ketalization of steroidal ketones using chlorotrimethylsilane as a catalyst
Tandon, Amita,Ray, Suprabhat
, p. 58 - 59 (2007/10/02)
Chlorotrimethylsilane (CTMS) was found to be an effective catalyst in the ketalization reaction of various steroidal ketones.A comparative study of the pTSA catalyzed and CTMS-catalyzed ketalization reactions of some steroidal ketones showed the superiority of CTMS as a catalyst in ketal formation.
