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A PROCESS FOR PREPARING BENZO[B]THIOPHENE DERIVATIVES

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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Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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Discovery of LSZ102, a potent, orally bioavailable selective estrogen receptor degrader (SERD) for the treatment of estrogen receptor positive breast cancer

In breast cancer, estrogen receptor alpha (ERalpha) positive cancer accounts for approximately 74% of all diagnoses, and in these settings, it is a primary driver of cell proliferation. Treatment of ERalpha positive breast cancer has long relied on endocrine therapies such as selective estrogen receptor modulators, aromatase inhibitors, and selective estrogen receptor degraders (SERDs). The steroid-based anti-estrogen fulvestrant (5), the only approved SERD, is effective in patients who have not previously been treated with endocrine therapy as well as in patients who have progressed after receiving other endocrine therapies. Its efficacy, however, may be limited due to its poor physicochemical properties. We describe the design and synthesis of a series of potent benzothiophene-containing compounds that exhibit oral bioavailability and preclinical activity as SERDs. This article culminates in the identification of LSZ102 (10), a compound in clinical development for the treatment of ERalpha positive breast cancer.

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Benzothiophene – Wikipedia,
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Benzo-thiophene-containing polymerizable compound (by machine translation)

This invention relates to a kind of polymerizable compounds are of formula I, the compounds of formula I can be polymerization and the liquid crystal composition, a liquid crystal display device. wherein X 1? X 7 independently represent H, or F CH 3; Y 1, Y 2 independently represent CH 3, CH 2 F, CHF 2 or CF 3. Is particularly suitable for the application of display or TV PSVA liquid crystal composition, in particular after running for a long time, with no or significantly reduced residual Image (image sticking). (by machine translation)

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Process for preparing benzoic acid derivative intermediates and benzothiophene pharmaceuticals

The invention relates to novel intermediates of formula VI wherein R1and R2each are independently C1-C4alkyl, or R1and R2together with the nitrogen to which they are attached form a piperidinyl, pyrrolidinyl, methylpyrrolidinyl, dimethylpyrrolidinyl, morpholino, dimethylamino, diethylamino, or 1-hexamethyleneimino ring; n is 2 or 3; and Y1is p-toluenesulfonyl-O-, methylsulfonyl-O-, trifluoromethylsulfonyl-O-, 2,2,2-trifluoroethylsulfonyl-O-, or trifluoroacetyl-O-; or a salt or solvate thereof. and processes for producing benzothiophenes of formula II wherein R4and R5are each independently a hydroxy protecting group.

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Benzothiophene – Wikipedia,
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2-Phenylbenzothiophene-based liquid crystalline semiconductors

We report herein the design and synthesis of some novel liquid crystalline semiconductors constructed from a biologically and pharmacologically active building block molecule, namely 6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene, presenting efficient luminescence and medium charge mobility rate. A first series of mesogenic 2-phenylbenzothiophene derivatives (nPBT) was simply and rapidly obtained in good yields by successive demethylation/alkylation reactions of the available methoxy precursor. The further stepwise oxidations moreover resulted in two new sets of the corresponding sulfoxide (nPBTO) and sulfone (nPBTO2) derivatives, respectively, that were also mesomorphic. The liquid crystalline behaviour was comprehensively characterized by DSC, POM and SAXS: all compounds exhibit smectic-like behaviour in agreement with their calamitic shape. More specifically, mesogens nPBT showed a SmA phase, with in addition, a higher ordered smectic phase at lower temperature. As for the oxidized mesogens, they displayed a SmA phase only, and over particularly large temperature ranges for the nPBTO with longer chain lengths (n ? 8). The photo-physical properties have also been studied both in solution and thin films, and the molecules were found to display strong absorption in the UV/vis domain and intense luminescence in the range of 400?650 nm (yellowish green light) in high quantum yields (up to 62%). Both absorption and luminescence were also found to be affected by the oxidation of the benzothiophene moiety. Finally, the semi-conducting behaviour of three PBT compounds in the various mesophases was investigated by photocurrent TOF technique. Hole mobility rates of ca. 4 ¡Á 10?3 cm2 V?1 s?1 were measured in the lower temperature ordered mesophase for all of them, with the best performances (temperature range and mobility values) however obtained for the shortest homolog (n = 6). With such highly reasonable mesomorphic, light-emitting and semiconducting functional features, as well as being cheap and easy to synthesize and to process, these materials become very attractive and may be incorporated into various kinds of electronic devices (OFET and OLED).

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Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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Characterization and structural analyses of trimethoxy and triethoxybenzo[b]thiophene

The crystal and molecular structures of two methoxybenzo [b] thiophenes have been determined by three-dimensional, single-crystal X-ray diffractometry. Both 3-(3?,4?,5?-trimethoxybenzoyl)-2-(4?-methoxyphenyl)-6- methoxybenzo[b]thiophene and 3-(3?,4?,5?-triethoxybenzoyl)-2-(4?-methoxyphenyl)-6- methoxybenzo[b]thiophene (hereafter referred to as I and II, respectively) crystallize in the triclinic centrosymmetric space group P1 (No. 2, C1) with two formula units per cell with a = 6.842(1) A, b = 12.602(2) A, c = 13.815(2) A, alpha = 94.80(1), beta = 98.27(2), and gamma = 100.59(2) and a = 10.600(1), b = 11.415(2), c = 12.137(2) A, alpha = 94.57(1), beta = 101.18(1), and gamma = 110.45(1), respectively. The phase problems were solved by direct methods and the respective final full-matrix least-squares refinements converged to R = 0.039 and 0.068. The structures differ in the orientation of the trimethoxy and triethoxy groups of the benzoyl ligands. The molecules in the crystal lattice are held together by van der Waals forces. Selected bond distances, angles, and torsion angles are tabularized as well as reference to the synthesis of the title compounds and peripheral studies.

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Benzothiophene – Wikipedia,
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Benzothiophenes, and formulations and methods using same

The invention provides novel benzothiophenes of the formula:wherein R1 is -H, -OH, -O(C1-C4 alkyl), -O-CO(C1-C6 alkyl), -OSO2(C4-C6 alkyl, or -OCOAr where Ar is optionally substituted phenyl; R2 is -H, -OH, -Cl, -Br, -O(C1-C4 alkyl), -OCO(C1-C6 alkyl), -OSO2(C4-C6 alkyl, or -OCOAr where Ar is optionally substituted phenyl; R3 is -H, -F, -Cl, -(C1-C4 alkyl), -CN, or -O(C1-C3 alkyl); R4 is -H, -F, -Cl, -(C1-C4 alkyl), -CN or -O(C1-C3 alkyl); R5 is -H, -F, -Cl, -(C1-C4 alkyl), or -O(C1-C3 alkyl); and R6 is -H, -F, -Cl, -(C1-C4 alkyl), or -O(C1-C3 alkyl); with the provisos that R3, R4, R5 and R6 can not all be hydrogen, and that when one of R3, R4, R5 or R6 is C1-C4 alkyl, no more than two of R3, R4, R5 and R6 can be hydrogen; Y is -CO-, -CHOH-, or -CH2-; R7 and R8 are independently C1-C4 alkyl or combine to form, with the nitrogen to which they are attached, 1-piperidinyl, 1-pyrrolidinyl, 1-hexamethyleneimino, or morpholino; or a pharmaceutically acceptable salt thereof. The present invention further provides pharmaceutical compositions containing compounds of formula I, optionally containing estrogen opr progestin, and the use of such compounds alone, or in combination with estrogen or progestin or alleviating the symptoms of post-menopausal syndrome, particularly osteoporosis, cardiovascular related pathological conditions, and estroge

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Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem

 

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From One-Pot NH-Sulfoximidations of Thiophene Derivatives to Dithienylethene-Type Photoswitches

Thiophene NH-sulfoximines have been synthesized using a one-pot NH-sulfoximidation reaction of thiophenes. The reactivity of the products was investigated, and the developed protocols were used for the synthesis of a new class of dithienylethene-type photoswitches containing a sulfoximidoyl group.

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Benzothiophene – Wikipedia,
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Methoxy-substituted 3-formyl-2-phenylindoles inhibit tubulin polymerization

The aim of this study was the identification of the essential structural elements in the 12-formyl-5,6-dihydroindolo[2,1-a]isoquinoline system required for the inhibition of tubulin polymerization which is understood to be the predominant mode of action of this class of cytostatics. Since 2- phenylindole forms the main fragment of this tetracycle, it was used as the basic structure and modified with respect to the number and positions of the oxygen functions in the aromatic rings. Further modifications related to the nitrogen, which was both replaced by oxygen and sulfur and alkylated. All derivatives were tested for cytostatic activity in human breast cancer cells (MDA-MB 231, MCF-7) and inhibition of tubulin polymerization. The spectrum of activity ranged from inactive to IC50 values of 35 nM (cell growth inhibition) and 1.5 muM (tubulin polymerization), respectively, for the most active derivative 3e (3-formyl-6-methoxy-2-(4-methoxyphenyl)indole). Although the correlation between antiproliferative activity and inhibition of tubulin polymerization was not very pronounced, all of the potent cytostatic agents in this study disrupted microtubule assembly completely at the standard concentration of 40 muM. By fluorescence microscopy it was demonstrated that the derivative 3e degrades the cytoskeleton in a similar fashion as colchicine does leading to the condensation of the microtubules around the nucleus after treatment. The comparison between hydroxy and methoxy derivatives revealed a striking difference between the 2-phenylindole derivatives and the indoloisoquinolines. In the 2-phenylindole series, the methoxy compounds were much more effective than the free phenols, whereas in the tetracyclic system the effect of the hydroxy derivatives exceeded that of the methylated compounds by 1 order of magnitude. Preliminary studies on the binding mode showed that both the 2-phenylindole derivatives and the indoloisoquinolines bind to the colchicine site on tubulin.

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Benzothiophene – Wikipedia,
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PROCESS FOR PREPARING RALOXIFENE HYDROCHLORIDE

Process for preparing raloxifene hydrochloride with a purity greater than 98% and low aluminium content comprising the following stages a) demethylation of 6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene in pyridine and hydrochloric acid to obtain 6-hydroxy?2-(4-hydroxyphenyl)benzo[b]thiophene in pyridine hydrochloride, b) acetylation of 6-hydroxy-2-(4?hydroxyphonyl)benzo[b]thiophene with an acetylating agent to obtain the corresponding 6-acetoxy-2-(4 acetoxyphenyl)benzo[b]thiophene, c) acylation of 6-acetoxy-2-(4-acetoxyphonyl)benzo[b]thlophene with 4-(2 piperidinoethoxy)benzoylchloride hydrochloride with aluminium trichloride in halogenated solvent to obtain 6-acetoxy-2-(4?acetoxyphenyl)-3-[4-(2 piperidinoethoxy)benzoyl]-benzo[b]thiophene, d) hydrolysis of 6-acetoxy-2-(4-acetoxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyll benzo[b]thiophene according to the following operating conditions: dl) treatment of 6-acetoxy-2-(4-acetoxyphonyl)-3-[4-(2?piperidinoethoxy)benzoyl]benzo[b]thiophene with alkaline hydroxide in alcohol solvent, d2) acidification of the product obtained in the preceding stage (dl) with a strong acid, to obtain the corresponding raloxifene salt with the strong acid, characterised in that the strong acid used in stage (d2) is concentrated hydrochloric acid.

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Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem