- Efficient synthesis of 3-benzoyl Benzo[b]thiophenes and raloxifene via Mercury(II)-Catalyzed cyclization of 2-alkynylphenyl alkyl sulfoxides
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The unique selective estrogen receptor modulator, Raloxifene (1), and antitubulin agent 2 were synthesized through the key intermediate, 4-methoxybenzyl 2-bromo-4-methoxyphenyl sulfoxide (6), respectively. It was found that compared with the o-sulfanyl aryl bromides, the sulfinyl group at ortho position accelerated the Sonogashira coupling reaction of aryl bromides. Thus, compound 6 was coupled with 3,4,5-trimethoxyphenyl acetylene, followed by mercury-catalyzed cyclization reaction afford compound 2 in 79% overall yield. Raloxifene (1) was prepared from compound 6 in four steps and 33% overall yield via coupling reaction with 1-trimethylsily-2-(4-tert-butyldimethylsiloxy)phenylethyne, mercury-catalyzed cyclization reaction, alkylation and demethylation.
- Wen, Shi-Ming,Lin, Cheng-Han,Chen, Chin-Chau,Wu, Ming-Jung
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p. 2493 - 2499
(2018/04/16)
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- Sulfoxide compound and method of producing benzothiophene derivatives using the same
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A sulfoxide compound and method of producing benzothiophene derivatives using the same are provided. The sulfoxide compound is represented by formula (I), wherein R1 and R2 are individually and independently benzoyl group; alkyl, acyl or silyl group of C1-C6 straight chain or branched chain; or alkenyl group of C3-C6 straight chain or branched chain; and X is halogen atom. The sulfoxide compound reacts with alkynyl compound, and then the synthesis efficiency of benzothiophene derivatives can be effectively increased.
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- Methods for Determining the Oncogenic Condition of Cell, Uses Thereof, and Methods for Treating Cancer
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The invention relates to methods for detecting the oncogenic condition of cells, including step where the amount of the OCDO compound in said cells is measured, and to the uses thereof. The invention further relates to OCDO inhibitors for use in methods for treating cancer.
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- Piperidine nucleophilic substitution without solvent: An efficient synthesis of raloxifene
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Mild and high-yielding synthesis is described for raloxifene via piperdine nucleophilic substitution of a new raloxifene intermediate 3-aroyl-2-aryl-substituted benzo[b]thiophenes, which is obtained by acylation of para-substituted benzoyl chlorides and 2-arylbenzo[b]thiophenes. The key step is solvent free and offers valuable advantages, such as low cost, and is suitable for industrial production.
- Yang, Yewei,Zhang, Tao,Huang, Wenhai,Shen, Zhenrong
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p. 3271 - 3276
(2015/10/06)
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- OXALIC ACID ADDITION SALTS AND/OR SOLVATES OF A SELECTIVE ESTROGEN RECEPTOR MODULATOR
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The present invention provides raloxifene oxalate, including derivatives thereof. In particular, the present invention provides solvates and/or hydrates of raloxifene oxalate, and polymorphs thereof. The present invention also provides processes for preparing the novel compounds, pharmaceutical compositions including the novel compounds and medical uses of the novel compounds.
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Page/Page column 28
(2014/09/29)
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- Synthesis of aryl ethers via a sulfonyl transfer reaction
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A general synthesis of aryl ethers from primary and secondary alcohols and aryl mesylates is presented. The reaction proceeds via a sulfonyl-transfer mechanism. In this paper, we compare the sulfonyl transfer reaction to Mitsunobu ether formation. The reaction can be employed in a multistep synthesis where the aryl mesylate is used as a phenol protecting group and then as an activating group for ether formation. This protecting/activating group strategy is demonstrated using raloxifene as the target.
- Sach, Neal W.,Richter, Daniel T.,Cripps, Stephan,Tran-Dubé, Michelle,Zhu, Huichun,Huang, Buwen,Cui, Jean,Sutton, Scott C.
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p. 3886 - 3889
(2012/09/22)
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- A process for preparing benzo[b]thiophene derivatives
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The present invention relates in general to the field of organic chemistry, and in particular to the preparation of benzo[b]thiophene derivatives. These benzo[b]thiophene derivatives are useful as intermediates in the synthesis of pharmaceutically active agents such as raloxifene or derivatives thereof.
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Page/Page column 32
(2011/06/10)
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- A PROCESS FOR PREPARING BENZO[B]THIOPHENE DERIVATIVES
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The present invention relates in general to the field of organic chemistry, and in particular to the preparation of benzo[b]thiophene derivatives. These benzo[b]thiophene derivatives are useful as intermediates in the synthesis of pharmaceutically active agents such as raloxifene or derivatives thereof.
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Page/Page column 47
(2011/05/06)
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- A PROCESS FOR THE PREPARATION OF 6-HYDROXY-2-(4-HYDROXYPHENYL)-3-[4-(2-PIPERIDINO ETHOXY) BENZOYL]BENZO[B]THIOPHENE
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The present invention related to a process for preparing 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(2- piperidinoethoxy)benzoyl]benzo[b]thiophene, compound of formula (I), said process comprising: deprotecting compound of formula (II) with base in dimethyl sulfoxide to yield substantially pure compound of formula (I) with HPLC purity of 99 % or more by area and optionally converting to its pharmaceutically acceptable salt.
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Page/Page column 14-15
(2009/03/07)
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- An efficient synthesis of raloxifene in ionic liquid: A Green Approach
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An efficient and green procedure for the synthesis of raloxifene has been developed by using Suzuki couplings, Friedel-Crafts acylation, and copper catalyzed coupling reactions in an ionic liquid.
- Shinde, Pravin S.,Shinde, Sandip S.,Renge, Atul S.,Patil, Gajanan H.,Rode, Ambadas B.,Pawar, Rajendra R.
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experimental part
p. 8 - 10
(2010/04/23)
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- ANTIRESORPTIVE MUTUAL SALT OF RALOXIFENE AND BISPHOSPHONIC ACID
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The mutual salt of raloxifene and bisphosphonic acid exhibits unexpectedly synergistic effects of two components to enhance bone mineral density (BMD), control blood-calcium density, and lower the serum cholesterol level.
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Page/Page column 8
(2008/06/13)
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- Method for the treatment or prevention of lower urinary tract symptoms
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This invention concerns a method for treatment or prevention of lower urinary tract symptoms with or without pelvic pain in an individual, said method comprising administering to the individual an effective amount of a selective estrogen receptor modulator, or an isomer, isomer mixture or a pharmaceutically acceptable salt thereof.
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- Intermediates and processes for preparing benzo (b) thiophenes
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The instant invention provides processes for preparing compounds of formula IV, V, and IX, having the structures provided hereinbelow: These compounds are useful intermediates in the further preparation of benzo[b] thiophenes.
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- Nucleophilic aromatic substitution on 3-aroyl-2-arylbenzothiophenes. Rapid access to raloxifene and other selective estrogen receptor modulators
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Versatile, mild and high yielding methods for nucleophilic aromatic substitution of 2-dialkylamino-1-ethoxides and related nucleophiles on 3- aroyl-2-arylbenzothiophene nuclei are presented. A short synthesis of raloxifene is detailed.
- Schmid, Christopher R.,Sluka, James P.,Duke, Kristin M.
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p. 675 - 678
(2007/10/03)
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- Process for the synthesis of benzothiophenes
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The instant invention provides improved processes for preparing benzothiophenes utilizing methanesulfonic acid.
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- Process for preparing benzo[b]thiophenes
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The preparation of benzo[b]thiophenes by the acylation of alkoxy protected starting materials followed by demethylation using essentially odorless thiol compounds are provided herewith. Demethylation may be carried out in the same reaction vessel without isolation of the acylated, protected material.
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- Process for the synthesis of benzothiophenes
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The instant invention provides improved processes for preparing benzothiophenes utilizing cation exchange resins.
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- Synergistic methodologies for the synthesis of 3-aroyl-2- arylbenzo[b]thiophene-based selective estrogen receptor modulators. Two concise syntheses of raloxifene
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Difunctionalized benzo[b]thiophene intermediates are prepared which allow fully independent elaboration of the 2-aryl position or the tether position of benzo[b]thiophene-based selective estrogen receptor modulators (SERMs). Two concise syntheses of the SERM raloxifene (Evista) are presented.
- Bradley, David A.,Godfrey, Alexander G.,Schmid, Christopher R.
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p. 5155 - 5159
(2007/10/03)
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- Amorphous benzothiophenes, methods of preparation, and methods of use
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The instant invention provides an amorphous form of a compound of formula I. wherein: R1and R3are independently hydrogen, -CH3,-CO(C1-C6alkyl), or -COAr, wherein Ar is optionally substituted phenyl; R2is selected from the group consisting of pyrrolidinyl, hexamethyleneimino, and piperidinyl; or a pharmaceutically acceptable salt or solvate thereof. Methods of preparing the material, as well as methods of using same, are also provided.
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- Process for the synthesis of benzothiophenes
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The instant invention provides improved processes for preparing benzothiophenes utilizing methanesulfonic acid.
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- Process for the synthesis of benzothiophenes
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The instant invention provides improved processes for preparing benzothiophenes utilizing cation exchange resins.
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- Demethylation process for preparing benzo[b]thiophenes
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The preparation of benzo[b]thiophenes by the acylation of alkoxy protected starting materials followed by demethylation using essentially odorless thiol compound (2-methyl-5-t-butyl benzenethiol) are provided herewith. Demethylation may be carried out in the same reaction vessel without isolation of the acylated, protected material.
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- Glucopyranoside benzothiophenes
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A compound of the formula STR1 or a pharmaceutically acceptable salt or solvate thereof. Also provided by the invention are methods of use of the above compounds, and processes for the preparation thereof.
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- Process for preparing 3-(4-aminoethoxy-benzoyl) benzo B!-thiophenes
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The invention provides a process for preparing 6-alkoxy-3-(4-alkoxyphenyl)benzo B!thiophenes in good yield on a manufacturing scale without generating a thick, potentially yield-reducing, paste. The invention also provides methods for converting a-(-alkoxyphenylthio)-4-alkoxyacetophenones into 6-hydroxy-2-(4-hydroxyphenyl)-3- 4-(2-aminoethoxy)benzoyl!benzo B!thiophenes via acylation of a dialkoxy benzo B!thiophene. Each of these preparations relies on an intramolecular cyclization of a dialkoxy acetophenone derivative to yield a benzo B!thiophene without generating a thick paste that lowers overall yields on a manufacturing scale.
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- Methods of use for inhibiting bone loss and lowering serum cholesterol
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A method of inhibiting bone loss or resorption, or lowering serum cholesterol, comprising administering to a human in need thereof a compound having the formula STR1 or a pharmaceutically acceptable salt or solvate thereof, in a low dosage amount. Also encompased by the invention is a a pharmaceutical formulation in unit dosage form comprising, per unit dosage, a low dosage amount.
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- Antiestrogens. 2. Structure-Activity Studies in a Series of 3-Aroyl-2-arylbenzothiophene Derivatives Leading to thien-3-yl>phenyl>methanone Hydrochloride (LY156758), a Remarkably Effective Estrogen Antagonist with On...
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In an effort to prepare nonsteroidal antiestrogens demonstrating greater antagonism and less intrinsic estrogenicity than those currently available, a series of 3-aroyl-2-arylbenzothiophene derivatives was synthesized.These compounds were prepared by Friedel-Crafts aroylation of appropriate O-protected 2-arylbenzothiophene nuclei with basic side-chain-bearing benzoyl chlorides followed by removal of the protective groups to provide the desired compounds containing both hydroxyl and basic side-chain functionality.A particularly useful method for the cleavage of aryl methoxy ethers without removal of (dialkylamino)ethoxy side chain functionality elsewhere in the molecule was found to be AlCl3/EtSH.The benzothiophene derivatives were tested for their ability to inhibit the growth-stimulating action of estradiol on the immature rat uterus.Seemingly minor changes in the side-chain amine moiety were found to have profound effects on the ability of the compounds to antagonize estradiol.Analogues having basic side chains containing cyclic (pyrrolidine, piperidine, and hexamethyleneamine) moieties were found to have less intrinsic estrogenicity and to antagonize estradiol action more completely than their noncyclic counterparts.The most effective antiestrogen in the series, compound 44, thien-3-yl>phenyl>methanone, elicited a modest uterotropic activity that did not increase with increasing dose.In antagonism of estradiol, 44 exhibited a degree of inhibition surpassing that of tamoxifen at any dose tested.The new benzothiophene antiestrogen was also shown to have high affinity for rat uterine cycloplasmic estrogen receptor and to be an inhibitor of the growth of DMBA-induced rat mammary tumors.
- Jones, Charles D.,Jevnikar, Mary G.,Pike, Andrew J.,Peters, Mary K.,Black, Larry J.,at al.
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p. 1057 - 1066
(2007/10/02)
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- Antiestrogenic and antiandrugenic benzothiophenes
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6-Hydroxy-2-(4-hydroxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]thiophene, its ethers and esters, and the physiologically acceptable acid addition salts thereof, are valuable antiestrogens and antiendrogens.
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- Synthesis of acylated benzothiophenes
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A group of 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(2-aminoethoxy)benzoyl]benzo[b]thiophenes are prepared by acylation of a methyl-protected starting compound followed by demethylation in a single reaction mixture.
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- Process for preparing 3-(4-aminoethoxybenzoyl)benzo[b]thiophenes
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The use of particularly advantageous protecting groups for the hydroxy groups of 6-hydroxy-2-(4-hydroxyphenyl)benzo[b]thiophenes provides a high-yielding process for the preparation of such compounds having a 4-(2-aminoethoxy)benzoyl 3-group.
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