Raloxifene

RALOXIFENE ANTICOAGULANTS - ORAL Possible 1 anticoagulant, effect which may take several weeks to develop Uncertain at present Monitor INR closely for several weeks 

RALOXIFENE LIPID-LOWERING DRUGS -ANION EXCHANGE RESINS Raloxifene levels may be i by colestyramine Colestyramine interrupts the enterohepatic circulation of raloxifene Avoid co-administration 

Sample preparation Mix 100 ng IS with 300 xL plasma, add 600 pL acetone, mix, let stand on ice for 10 min, centrifuge. Evaporate the supernatant to dr5mess under reduced pressure, reconstitute the residue with 100 pL 500 mM pH 9.0 sodium carbonate and 100 pL dichloromethane, mix thoroughly, centrifuge, inject a 40 pL aliquot of the organic layer. 

Column 10 pm Zorbax C8 or LiChrosorb C8 Mobile phase MeCNilOO mM pH 4.0 sodium acetate 50 50 Flow rate 2 Injection volume 40 

Internal standard (4-(2-(dimethylamino)ethoxy)phenyl)(6-hydro -2-(4-hydroxjq)hen-yDbenzo [b] thien-3-yl)methanone (3.9) 

Lindstrom, T.D. Whitaker, N.G. Whitaker, G.W. Disposition and metabohsm of a new benzothiophene antiestrogen in rats, dogs and monkeys, Xenobiotica, 1984,14, 841-847. 

Sample preparation Inject a 1 pL aliquot of a solution in MeOHiwater 10 90. 

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Selective oestrogen receptor modulators (SERMs, e.g. Raloxifene) Calcitriol and analogues (limited use)... 

Selective estrogen receptor modulators (SERMs) are synthetic compounds with partially agonistic and partially antagonistic estrogenic properties. In bone, SERMs inhibit bone resorption via the mechanisms known for estrogens. Major SERMs are tamoxifen, a triphenylethylene compound, and raloxifene. In postmenopausal women, the latter has been shown to prevent bone loss and to reduce fracture risk by 40%. 

STAR trial (Study of tamoxifen and raloxifene), which was completed in 2006, demonstrated additional utility of raloxifene in the prevention and treatment of breast cancer. In fact, the absence of associated uterotrophic effects with raloxifene suggests that it may be a safer agent than tamoxifen for use as a chemopreventative in high-risk postmenopausal women [3] therefore, raloxifene has very recently become a new option for breast cancer prevention now available for physicians and their patients. 

Benzothiophenes have always been of interest for medicinal chemistry and can be found in a number of marketed drugs such as Sertaconazole (Gineder-mofix), Zileuton (Leutrol) and Raloxifene (Evista). The classical synthesis of benzo thiophenes starts from thiophenols, reacting with bromoacetaldehyde dimethyl acetal, followed by cycUzation using strong acid. An alternative and more convenient route was also described starting from benzaldehydes which... 

C Hj 02 123-11-5) see Anisindione Diltiazem Fenoldopam mesilate Mepyramine Raloxifene hydrochloride m-anisidine... 

CisHisLNjO 154371-62-7) see Eprosartan tert-butyl 4,4 -dimethoxy-a-stilbenyl sulfide (C20H24O2S) see Raloxifene hydrochloride tert-butyl 4,4 -dimethoxy-a-stilbenyl sulfoxide (C20H24O3S 186408-54-8) see Raloxifene hydrochloride l-butyl-2-(2,6-dimethylanilinocarbonyl)pyridinium bromide... 

C7H,4C1N 1932-03-2) see Cloperastine Fenpiverinium bromide Raloxifene hydrochloride... 

C, ill, i02 120-44-5) see Diethylstilbestrol Mofezolac Raloxifene hydrochloride deoxyanisoin oxime... 

C3H4O3 96-49-1) see Hexcarbacholine bromide Raloxifene hydrochloride ethylene chlorohydrin... 

Ci,HijNOjS i55//-f5-0) see Meloxicam methyl 4-(2-hydroxyethoxy)benzoate (C],)H 204 3204-73-7) see Raloxifene hydrochloride methyl A -(2-hydroxyethyl)dithiocarbamate (CjHijNOSi 56158-48-6) see Flomoxef A -methyl-At-(2-hydroxyethyl)guanidine phosphate (C4H,4Nj05P 33018-83-6) see Creatinolfosfate 5-methyl-10-hydroxyimino-10,ll-dihydro-5H-dibenz-[6/lazepine... 

C16H14O6S3 84449-65-0) see Raloxifene hydrochloride (S)-2-[(methylsulfonyl)oxy]propanoic acid ethyl ester (QHijOjS 63696-99-1) see Naproxen (5)-2-[(methylsulfonyl)oxy]propanoyl chloride (C4H7CIO4S 85277-55-0) see Naproxen 2-methylsulfonylphenothiazine (C13H11NO2S2 23503-68-6) see Metopimazine Sulforidazine... 

C 4H2(,C1N02 24465-45-0) see Phenoperidine phenyl 2-piperidinoethyl ether hydrochloride (CnH iClNO 92196-25-3) see Raloxifene hydrochloride trfl s-4-phenyl-L-proline (C11H13NO2 96314-26-0) see Fosinopril... 

SCHEME 10.13 Di-QMs formed from raloxifene and DMA. 4-Fluoro substitution prevents di-QM formation. 

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