Detail of "5189-40-2"

Reference

A rational approach to the design of anti-estrogens: the case of hydroxylated triphenylethylene derivatives

A rational approach to the design of anti-estrogens: the case of hydroxylated triphenylethylene derivatives. Pons, M.; Michel, F.; Bignon, E.; Crastes de Paulet, A.; Gilbert, J.; Miquel, J. F.; Precigoux, G.; Hospital, M.; Ojasoo, T.; Raynaud, J. P. (INSERM, Montpellier 34100, Fr.Some commonly used reagents like 89986-17-4 is used in this experiment.). Prog. Cancer Res. Ther., 31(Horm. Cancer 2), 27-36 (English) 1984. CODEN: PCRTDK. ISSN: 0145-3726. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) Section cross-reference(s): 1 Estrogen receptor (ER) structure-affinity and structure-activity relations were examd. for a series of hydroxylated 2,3,3-triphenylacrylonitrile (I) derivs. (R = R1 = R2 = H or OH). Competition with [3H]estradiol for the cytosolic ERs of immature rat or mouse uterus were performed at 0° for 2 h and 25° for 5 h. The unsubstituted compd. (I; R = R1 = R2 = H) [6304-33-2] had no affinity for the ER whereas the deriv. of I in which R= OH, R1 = R2 = H had a relative binding affinity (RBA) as high as estradiol at 0°. The deriv. in which R = R2 = H, R1 = OH had a RBA ~10 times lower. Compds in which R = R1 = OH, R2 = H; R = R2 = OH, R1 = H; and R = H, R1 = R2 = OH had high RBAs at 0° and even higher ones at 25°. The higher RBAs at 25° compared to 0° suggests that the presence of 2 hydroxyl groups is important for the stability of the complex formed with ER. The dihydroxylated compd. deacetylated cyclofenil [5189-40-2] had a relatively high RBA compared to the parent cyclofenil [2624-43-3] with no free hydroxyl groups. The trihydroxylated compd. (I, R = R1 = R2 = OH) also had a fairly high RBA and formed a stable complex with the ER. Apparently, high affinity is only obtained with these compds. when R is hydroxylated and its phenol ring plays an important role in interacting with a subsite of ER. This phenol ring may take the place of the estradiol A ring in the ER site. Contributions of the other phenol rings to ER binding are also considered and a model is presented which accounts for both the H-bonding of the phenol rings and the hydrophobic interactions of the Ph rings. .

Selective inhibition of proteoglycan and hyaluronate synthesis in chondrocyte cultures by cyclofenil diphenol, a non-steroidal weak estrogen

Selective inhibition of proteoglycan and hyaluronate synthesis in chondrocyte cultures by cyclofenil diphenol, a non-steroidal weak estrogen. Mason, Roger M.; Lineham, Jennifer D.; Phillipson, Margaret A.; Black, Carol M. (Dep. Biochem., Charing Cross Hosp. Med. Sch., London W6 8RF, UK). Biochem. J., 223(2), 401-12 (English) 1984. CODEN: BIJOAK. ISSN: 0306-3275. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) Cyclofenil diphenol [5189-40-2], a weak nonsteroidal estrogen, in the presence of concns. of albumin just sufficient to keep it in soln., dose dependently inhibited the synthesis of [35S]proteoglycans, [3H]glycoproteins, 3H-labeled hyaluronate [9004-61-9], and [3H]proteins in primary cultures of chondrocytes from the Swarm rat chondrosarcoma. When excess albumin was present, conditions were found (90 mg cyclofenil diphenol and 4 mg albumin/mL of culture medium) which completely inhibited [35S]proteoglycan and [3H]hyaluronate synthesis but had little effect on [3H]protein or [3H]glycoprotein synthesis. The time of onset of inhibition of [35S]proteoglycan synthesis by cyclofenil diphenol was very rapid (half-time <25 min) and incompatible with an action mediated through suppression of proteoglycan core protein synthesis. Cyclofenil diphenol inhibited the synthesis of [35S]chondroitin sulfate chains onto p-nitrophenyl b-D-xyloside in the cultures. Cyclofenil diphenol had little effect on the secretion from chondrocytes of [35S]proteoglycans synthesized immediately prior to treatment. Chondrocyte cultures treated with cyclofenil diphenol recovered their biosynthetic activities almost completely within 3 h of removing the compd. from the culture medium. Cyclofenil diphenol had a similar inhibitory action on the synthesis of [35S]proteoglycans in secondary cultures of human dermal fibroblasts from both normal subjects and patients with systemic sclerosis. Apparently, cyclofenil diphenol inhibits the synthesis of [35S]proteoglycans by interfering with the formation of the glycosaminoglycan side chains of these mols. in the Golgi app. of cells. The action may be due to disturbance of Golgi membrane organization by the compd.