- Concise synthesis and biological evaluation of 2-Aryl-3-Anilinobenzo[b]thiophene derivatives as potent apoptosis-inducing agents
-
Many clinically used agents active in cancer chemotherapy exert their activity through the induction of cell death (apoptosis) by targeting microtubules, altering protein function or inhibiting DNA synthesis. The benzo[b]thiophene scaffold holds a pivotal place as a pharmacophore for the development of anticancer agents, and, in addition, this scaffold has many pharmacological activities. We have developed a flexible method for the construction of a new series of 2-aryl-3-(3,4,5-trimethoxyanilino)-6-methoxybenzo[b]thiophenes as potent antiproliferative agents, giving access to a wide range of substitution patterns at the 2-position of the 6-methoxybenzo[b]thiophene common intermediate. In the present study, all the synthesized compounds retained the 3-(3,4,5-trimethoxyanilino)-6-methoxybenzo[b]thiophene moiety, and the structure–activity relationship was examined by modification of the aryl group at its 2-position with electron-withdrawing (F) or electron-releasing (alkyl and alkoxy) groups. We found that small substituents, such as fluorine or methyl, could be placed in the para-position of the 2-phenyl ring, and these modifications only slightly reduced antiproliferative activity relative to the unsubstituted 2-phenyl analogue. Compounds 3a and 3b, bearing the phenyl and para-fluorophenyl at the 2-position of the 6-methoxybenzo[b]thiophene nucleus, respectively, exhibited the greatest antiproliferative activity among the tested compounds. The treatment of both Caco2 (not metastatic) and HCT-116 (metastatic) colon carcinoma cells with 3a or 3b triggered a significant induction of apoptosis as demonstrated by the increased expression of cleaved-poly(ADP-ribose) polymerase (PARP), receptor-interacting protein (RIP) and caspase-3 proteins. The same effect was not observed with non-transformed colon 841 CoN cells. A potential additional effect during mitosis for 3a in metastatic cells and for 3b in non-metastatic cells was also observed.
- Romagnoli, Romeo,Preti, Delia,Hamel, Ernest,Bortolozzi, Roberta,Viola, Giampietro,Brancale, Andrea,Ferla, Salvatore,Morciano, Giampaolo,Pinton, Paolo
-
-
- Synthesis of 2-Substituted Benzothio(seleno)phenes and Indoles via Ag-Catalyzed Cyclization/Demethylation of 2-Alkynylthio(seleno)anisoles and 2-Alkynyldimethylanilines
-
An Ag-catalyzed cyclization/demethylation of 2-alkynylthio(seleno)anisoles and 2-alkynyldimethylanilines is described and applied for the construction of valuable benzothio(seleno)phenes as well as indoles. Various 2-substituted benzothio(seleno)phenes and indoles were obtained in good to excellent yields under mild reaction conditions with low catalyst loading. An application of this new method is also exemplified with a concise synthesis of a bioactive molecule precursor. Furthermore, a conceivable reaction mechanism is proposed with supports from isotope-exchange experiments.
- Cai, Tao,Feng, Chengjie,Shen, Fangqi,Bian, Kejun,Wu, Chunlei,Shen, Runpu,Gao, Yuzhen
-
p. 653 - 656
(2020/12/23)
-
- Benzothiophene derivatives as selective estrogen receptor covalent antagonists: Design, synthesis and anti-ERα activities
-
Estrogen receptor α emerged as a well validated therapeutic target of breast cancer for decades. However, approximately 50% of patients who initially responding to standard-of-care (SoC), such as undergo therapy of Tamoxifen, generally inevitably progress to an endocrine-resistance ER+ phenotype. Recently, selective estrogen receptor covalent antagonists (SERCAs) targeted to ERα have been demonstrated as a therapeutic alternative. In the present study, series of novel 6-OH-benzothiophene (BT) derivatives targeting ERα and deriving from Raloxifene were designed, synthesized, and biologically evaluated as covalent antagonists. Driven by the antiproliferative efficacy in ER+ breast cancer cells, our chemical optimization finally led to compound 19d that with potent antagonistic activity in ER+ tumor cells while without agonistic activity in endometrial cells. Moreover, the docking simulation was carried out to elucidate the binding mode, revealing 19d as an antagonist and covalently binding to the cysteine residue at the 530 position of ER helix H11.
- Bai, Chengfeng,Luo, Guoshun,Ren, Shengnan,Wu, Shuangjie,Xiang, Hua,Zhu, Meiqi
-
-
- Facile C-S Bond Cleavage of Aryl Sulfoxides Promoted by Bronsted Acid
-
A method for the Bronsted acid promoted desulfination of aryl sulfoxides is presented. In the presence of a thiol, electron-rich sulfoxides undergo C-S bond cleavage to give the corresponding protodesulfinated arenes and disulfides.
- Brutiu, Bogdan R.,Klose, Immo,Maulide, Nuno
-
supporting information
p. 488 - 490
(2021/03/09)
-
- Well-Defined Palladium N-Heterocyclic Carbene Complexes: Direct C-H Bond Arylation of Heteroarenes
-
A series of palladium N-heterocyclic carbene (NHC) complexes of type trans-{(NHC)PdCl2L} (L = C5H5N, 3-ClC5H4N, and PPh3) (3-5) have been developed as efficient precatalysts for direct C-H bond arylation of various heteroarenes. In particular, an in situ generated new NHC ligand derived from {1,3-di-(2,6-diethylphenyl)acenaphtho[1,2-d] imidazolium} chloride (2) is used for the stabilization of the palladium metal center. Among the screened palladium precatalysts (3-5), the most active PEPPSI themed complex (3) was successfully employed toward direct C-H bond arylation of various heteroarenes and aryl bromides. A range of functional groups on aryl bromides as well as on heteroarenes sustained throughout the standard reaction conditions for easy access of various arylated heterocyclic compounds. Significantly, the utility of the protocol was demonstrated by the effective synthesis of a precursor of raloxifene, a selective estrogen receptor modulator.
- Kumar, Anuj,Kumar, Manoj,Verma, Akhilesh K.
-
p. 13983 - 13996
(2020/11/20)
-
- Transition-Metal-Free Synthesis of Heterobiaryls through 1,2-Migration of Boronate Complex
-
The synthesis of a diverse range of heterobiaryls has been achieved by a transition-metal-free sp2–sp2 cross-coupling strategy using lithiated heterocycle, aryl or heteroaryl boronic ester and an electrophilic halogen source. The construction of heterobiaryls was carried out through electrophilic activation of the aryl–heteroaryl boronate complex, which triggered 1,2-migration from boron to the carbon atom. Subsequent oxidation of the intermediate boronic ester afforded heterobiaryls in good yield. A comprehensive 11B NMR study has been conducted to support the mechanism. The cross coupling between two nucleophilic cross coupling partners without transition metals reveals a reliable manifold to procure heterobiaryls in good yields. Various heterocycles like furan, thiophene, benzofuran, benzothiophene, and indole are well tolerated. Finally, we have successfully demonstrated the gram scale synthesis of the intermediates for an anticancer drug and OLED material using our methodology.
- Paul, Swagata,Das, Kanak Kanti,Manna, Samir,Panda, Santanu
-
supporting information
p. 1922 - 1927
(2020/02/04)
-
- ESTROGEN RECEPTOR TARGETING ANTAGONISTS
-
The present disclosure relates to compounds that act as antagonists via binding to the ER ligand binding domain non-covalently or covalently, or act as both antagonists and ER protein degraders, and the synthesis of the same. Further, the present disclosure teaches the utilization of such compounds in a treatment for proliferative diseases, including cancer, particularly breast cancer, and especially ER+ breast cancer.
- -
-
Paragraph 0030; 0103-0105
(2020/05/07)
-
- Nickel-catalyzed and Li-mediated regiospecific C-H arylation of benzothiophenes
-
A nickel-based catalytic system for the regiospecific C2-H arylation of benzothiophene has been established. NiCl2(bpy) is used as a catalyst in combination with LiHMDS as a base in dioxane. The catalytic system is applicable to a variety of functionalized benzothiophenes, as well as other heteroarenes including thiophene, benzodithiophene, benzofuran and selenophene in combination with iodo aryl electrophiles. The role of LiHMDS as a uniquely potent base and a postulated mechanism are discussed. The applicability of this system is finally demonstrated for the synthesis of an intermediate of an active pharmaceutical ingredient.
- Canivet, Jér?me,Grousset, Léonie,Hisler, Ga?lle,Mohr, Yorck,Quadrelli, Elsje Alessandra,Roux, Yoann,Wisser, Florian M.
-
supporting information
p. 3155 - 3161
(2020/06/19)
-
- Preparation of Benzothiophenes and Benzoselenophenes from Arylamines and Alkynes via Radical Cascade Reactions
-
An intermolecular radical cascade reaction between readily prepared o-methylthio-arylamines or o-methylselanyl-arylamines and alkynes for the preparation of valuable benzothiophenes or benzoselenophenes is reported. These transformations occur efficiently with complete regioselectivity and the products are obtained in moderate to good yields. The current protocol is successfully applied to the synthesis of the key intermediates of the drug raloxifene and an AT1receptor antagonist.
- Zang, Hao,Sun, Jian-Guo,Dong, Xin,Li, Ping,Zhang, Bo
-
supporting information
p. 1746 - 1752
(2016/06/09)
-
- Visible light photocatalytic synthesis of benzothiophenes
-
The photocatalytic reaction of o-methylthio-arenediazonium salts with alkynes yields substituted benzothiophenes regioselectively through a radical annulation process. Green light irradiation of eosin Y initiates the photoredox catalysis. The scope of the reaction was investigated by using various substituted diazonium salts and different alkynes.
- Hari, Durga Prasad,Hering, Thea,Koenig, Burkhard
-
p. 5334 - 5337,4
(2012/12/12)
-
- PROCESS FOR THE PREPARATION OF RALOXIFENE HYDROCHLORIDE
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The present invention provides an improved process for the preparation of α-(3- methoxyphenylthio)-4-methoxyacetophenone. The present invention also provides a process for the preparing free flowing solid of 6-methoxy-2-(4-methoxyphenyl)- benzo[b]-thiophene. The present invention further provides a process for the preparation of substantially pure 6-methoxy-2-(4-methoxyphenyl)-benzo[b]-thiophene. The present invention further provides a process for purification of raloxifene hydrochloride.
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Page/Page column 9
(2011/11/06)
-
- An efficient synthesis of raloxifene in ionic liquid: A Green Approach
-
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)
-
- Process for preparing benzoic acids
-
An improved process for the preparation of 4[(2-piperidin-1-yl)ethoxy]benzoic acid derivatives, comprising reacting a haloalkyl amine of formula (III) with a compound of formula (IV) in the presence of a hydrated inorganic base in an appropriate solvent.
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Page/Page column 7
(2010/02/12)
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- An efficient one-pot synthesis of substituted 2-arylbenzo[b]thiophene derivatives
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This communication describes an efficient one-pot procedure for the synthesis of 2-arylbenzo[b]thiophene derivatives via reaction of o-halo or nitro aryl carbonyl compounds with benzyl mercaptans in the presence of an excess of anhydrous K2CO3 at elevated temperature.
- Patel, Meena V.,Rohde, Jeffrey J.,Gracias, Vijaya,Kolasa, Teodozyj
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p. 6665 - 6667
(2007/10/03)
-
- Process for the synthesis of vinyl sulfoxides
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The present invention is directed to a new process for the synthesis of vinyl sulfoxides, in particular diarylvinyl sulfoxides
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-
Page column 15
(2010/01/31)
-
- Toward selective ERβ agonists for central nervous system disorders: Synthesis and characterization of aryl benzthiophenes
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In an effort to identify selective for the estrogen receptor subtype ERβ, a series of aryl benzthiophenes was synthesized. In a radioligand binding assay and reporter gene assat in HeLa and SH-SY5Y cells, compound were characterized as ERβ-selective agonists. By targeting ERβ in the brain, these compounds could lead to drugs able to separate the beneficial effects of estrogens on mood, learning, and memory from side effects such as the stimulation of edometrial and breast cancer.
- Schopfer, Ulrich,Schoeffter, Philippe,Bischoff, Serge F.,Nozulak, Joachim,Feuerbach, Dominik,Floersheim, Philipp
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p. 1399 - 1401
(2007/10/03)
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- Intermediates and a process for preparing benzo[B]thiophenes
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The instant invention provides intermediates and processes for the preparation of compounds of formula IV wherein: n is 0, 1, or 2; R is hydrogen or C1-C4 alkyl; X1 is hydrogen, cyano, 4-hydroxybenzoyl, 4-halobenzoyl, or 4-(C1-C4 alkoxy)benzoyl; Y is NR4R5, 4-hydroxyphenyl, or 4-(C1-C4 alkoxy)phenyl; and R4 and R5 are independently hydrogen or C1-C4 alkyl.
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- 2-arylbenzo[B]thiophenes useful for the treatment of estrogen deprivation syndrome
-
This invention provides methods which are useful for the inhibition of the various medical conditions associated with estrogen deprivation syndrome including osteoporosis and hyperlipidemia utilizing compounds of formula I:
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-
- Treatment of central nervous system disorders with selective estrogen receptor modulators
-
The present invention provides a method of treating depression, mood swings, or Alzheimer's disease in a patient in need of such treatment by administering a selective estrogen receptor modulating compound of the formula in which R1 and R2 are independently hydroxy and alkoxy of one to four carbon atoms; and R3 and R4 are independently methyl or ethyl, or R3 and R4, taken together with the nitrogen atom to which they are attached, form a pyrrolidino, methyl-pyrrolidino, dimethylpyrrolidino, piperidino, morpholino, or hexamethyleneimino ring.
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-
- Sulfur-alkyne cyclizations for formation of dihydrothiophenes and annulated thiophenes
-
Cycloisomerization of homopropargylic thiols to dihydrothiophenes is promoted by group VI metal carbonyls. Related thiacyclization transformations under basic and radical conditions are also described, including regioselective formation of benzothiophenes from aryl methyl sulfides and alkynes.
- McDonald, Frank E.,Burova, Svetlana A.,Huffman Jr., Larry G.
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p. 970 - 974
(2007/10/03)
-
- A facile synthesis of 3-aryl-substituted-benzothiophenes via a Lewis acid mediated cyclization of 2-arylthio-acetophenones
-
The boron trifluoride-etherate mediated cyclization of 2-arylthio- ketones 1a-h at ambient temperature gave 3-aryl-substituted benzothiophenes 2a-h in excellent yield. None of the rearranged 2-aryl-substituted benzothiophenes were observed.
- Kim, Seongkon,Yang, Jane,DiNinno, Frank
-
p. 2909 - 2912
(2007/10/03)
-
- A new anti-tubulin agent containing the benzo[b]thiophene ring system
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A new type of inhibitor of tubulin polymerization was discovered based on the 3-aroyl-2-arylbenzo[b]thiophene molecular skeleton. The lead compound in this series, 2-(4'-methoxyphenyl)-3-(3',4',5'-trimethoxybenzoyl)-6- methoxybenzo[b]thiophene 1, inhibited tubulin polymerization, caused an increase in the mitotic index of CA46 Burkitt lymphoma cells, and inhibited the growth of several human cancer cell lines.
- Pinney, Kevin G.,Bounds, A. Dawn,Dingeman, Koren M.,Mocharla, Vani P.,Pettit, George R.,Bai, Ruoli,Hamel, Ernest
-
p. 1081 - 1086
(2007/10/03)
-
- Synthesis of 3-[4-(2-aminoethoxy)-benzoyl]-2-aryl-6-hydroxy-benzo[B]thiophenes
-
The present invention is directed to chemical processes for preparing 2-aryl-6-hydroxy-3-[4-(2-aminoethoxyl)benzoyl]benzoyl]benzo[b]-thiophenes.
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-
-
- Process for preparing benzo[b]thiophenes
-
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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- Benzothiophene compounds, intermediates, compositions, and methods
-
The present invention provides intermediate compounds and processes for the preparation of compounds of formula I STR1 wherein R1a is --H or --OR7a in which R7a is --H or a hydroxy protecting group; R2a is --H, halo, or --OR8a in which R8a is --H or a hydroxy protecting group; R3 is 1-piperidinyl, 1-pyrrolidino, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidino, 4-morpholino, dimethylamino, diethylamino, diisopropylamino, or 1-hexamethyleneimino; n is 2 or 3; and Z is --O-- or --S--; or a pharmaceutically acceptable salt thereof.
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- Benzothiophene compounds, intermediates, compositions, and methods
-
The present invention provides a method for inhibiting endometriosis comprising administering to a woman an effective amount of a compound of formula I STR1 wherein R1a is --H or --OR7a in which R7a is --H or a hydroxy protecting group; R2a is --H, halo, or --OR8a in which R8a is --H or a hydroxy protecting group; R3 is 1-piperidinyl, 1-pyrrolidino, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidino, 4-morpholino, dimethylamino, diethylamino, diisopropylamino, or 1-hexamethyleneimino; n is 2 or 3; and Z is --O-- or --S--; or a pharmaceutically acceptable salt thereof.
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-
- Benzothiophene compounds, intermediates, compositions, and methods
-
A method for alleviating the symptoms of post-menopausal syndrome comprising administering to a woman in need thereof an effective amount of a compound of formula I wherein R1a is --H or --OR7a in which R7a is --H or a hydroxy protecting group; R2a is --H, halo, or --OR8a in which R8a is --H or a hydroxy protecting group; R3 is 1-piperidinyl, 1-pyrrolidino, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidino, 4-morpholino, dimethylamino, diethylamino, diisopropylamino, or 1-hexamethyleneimino; n is 2 or 3; and Z is --O-- or --S--; or a pharmaceutically acceptable salt thereof, and further comprising administering to said woman an effective amount of progestin.
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-
- Benzothiophene compounds, intermediates, compositions, and methods
-
A method for alleviating the symptoms of post-menopausal syndrome comprising administering to a woman in need thereof an effective amount of a compound of formula I wherein R1a is -H or -OR7a in which R7a is -H or a hydroxy protecting group; R2a is -H, halo, or -OR8a in which R8a is -H or a hydroxy protecting group; R3 is 1-piperidinyl, 1-pyrrolidino, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidino, 4-morpholino, dimethylamino, diethylamino, diisopropylamino, or 1-hexamethyleneimino; n is 2 or 3; and Z is -O-or -S-; or a pharmaceutically acceptable salt thereof, and further comprising administering to said woman an effective amount of estrogen.
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-
- Application of heterogeneous acid catalysts to the large-scale synthesis of 2-and 3-(p-methoxyphenyl)-6-methoxybenzo[b]thiophenes
-
2-(p-Methoxyphenyl)-6-methoxybenzothiophene (3) was synthesized by acid-catalyzed cyclization and rearrangement of the β-ketosulfide precursor 1. The use of Amberlyst 15 resin as a catalyst for the cyclization increased the isomer ratio from 75: 25 to 88:12, compared to a conventional approach using polyphosphoric acid (PPA). Although solid acid catalysts were also evaluated for the rearrangement, a two-phase mixture of methanesulfonic acid in toluene was found to be the best alternative to the use of PPA for this reaction. The rearrangement, which was shown to be equilibrium controlled, was driven towards completion by crystallization of the product as it formed. An Amberlyst 15 catalyzed cyclization, combined with an MsOH-catalyzed rearrangement, raised the overall isolated yield from 70 to 80%, and difficulties associated with the use of PPA on a large scale were eliminated. This process has been successfully scaled to a pilot plant and manufacturing scale.
- Vicenzi, Jeffrey T.,Zhang, Tony Y.,Robey, Roger L.,Alt, Charles A.
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-
- Benzothiophene compounds, and uses and formulations thereof
-
Benzothiophenes, and uses and formulations thereof, are provided by the present invention. The compounds are of the formula wherein R1and R2are independently -OH, -OCO(C1-C6alkyl), -O(CO)O(C1-C6alkyl), -OCO-Ar, where Ar is phenyl or substituted phenyl, or -O(CO)Ophenyl; and R3is a substituent in the 3 or 4 position of the phenyl ring selected from the group of -H, -Cl, -Br, -CH3, or -CH2CH3; or a pharmaceutically acceptable salt or solvate thereof, with the proviso that when R1and R2are both hydroxy, R3is not -H, -CH3, or -CH2CH3.
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- Intermediates and a process for preparing benzo[b]thiophenes
-
The present invention provides a process for preparing a class of compounds having the structure wherein: n is 0, 1, or 2; R is hydrogen or C1-C4 alkyl; X1 is hydrogen, cyano, 4-hydroxybenzoyl, 4-halobenzoyl, or 4-(C1-C4 alkoxy)benzoyl; Y is NR4R5, 4-hydroxyphenyl, or 4-(C1-C4 alkoxy)phenyl; R4 and R5 are independently hydrogen or C1-C4 alkyl. The compounds are useful intermediates in the preparation of a class of compounds including the selective estrogen receptor modulating compound 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(2-piperidinoethoxy)benzoyl]benzo[b]-thiophene (raloxifene).The present invention provides a process for preparing a class of compounds having the structure wherein: n is 0, 1, or 2; R is hydrogen or C1-C4 alkyl; X is hydrogen, cyano, 4-hydroxybenzoyl, 4-halobenzoyl, or 4-(C1-C4 alkoxy)benzoyl; Y is NRR, 4-hydroxyphenyl, or 4-(C1-C4 alkoxy)phenyl; R and R are independently hydrogen or C1-C4 alkyl. The compounds are useful intermediates in the preparation of a class of compounds including the selective estrogen receptor modulating compound 6-hydroxy-2-(4-hydroxyphenyl)-3-?4-(2-piperidinoethoxy)benzoylübenzo?b ü-thiophene (raloxifene).
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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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- 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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- Process for preparing 2-substituted benzo[b]thiophene compounds and intermediates thereof
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The present invention provides processes for preparing 2-substituted benzo[b]thiophene compounds, some of which are useful as intermediates for preparing pharmaceutically-active compounds and others which are useful, inter alia, for the treatment of osteoporosis in postmenopausal women.
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- Process for the synthesis of benzo[b]thiophenes
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The present invention is directed to new processes for the synthesis of 2-aryl benzo[b]thiophenes.
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- Process for preparing benzoic acid derivative intermediates and benzothiophene pharmaceutical agents
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Novel processes for producing compounds of formula I STR1 wherein R1 and R2 each are independently C1 -C4 alkyl, or combine to form piperidinyl, pyrrolidinyl, methylpyrrolidinyl, dimethylpyrrolidinyl, morpholino, dimethylamino, diethylamino, or 1-hexamethyleneimino; and n is 2 or 3; or a pharmaceutically acceptable salt thereof employing alkylacetate solvents are provided.
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- Process for the synthesis of benzo[b]thiophenes
-
The present invention is directed to a process for the synthesis of 2-arylbenzo[b]thiophenes.
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- Diarylvinyl sulfoxides
-
The present invention is directed to new diarylvinyl sulfoxides.
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- Process for preparing 3-(4-aminoethoxy-benzoyl) benzo B!-thiophenes
-
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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- Process for the synthesis of vinyl sulfenic acid derivatives
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The present invention is directed to a new process for the synthesis of vinyl sulfenic acid derivatives. These compounds are useful for the synthesis of benzo b!thiophenes, in particular 2-aryl-benzo b!thiophenes.
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- Process for the synthesis of benzo[b]thiophenes
-
The present invention is directed to a new process for the synthesis of 2-aryl benzo[b]thiophenes, and to novel intermediates therefor.
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- Benzothiophene compounds, intermediates, compositions, and method for inhibiting restenosis
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The present invention provides pharmaceutically active compounds of formula I STR1 wherein R1 is --H, --OH, --O(C1 -C4 alkyl), --OCOC6 H5, --OCO(C1 -C6 alkyl), or --OSO2 (C2 -C6 alkyl); R2 is --H, --OH, --O(C1 -C4 alkyl), --OCOC6 H5, --OCO(C1 -C6 alkyl), --OSO2 (C2 -C6 alkyl), or halo, providing when Z is --S--, R2 is not halo; R3 is 1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidinyl, 4-morpholino, dimethylamino, diethylamino, diisopropylamino, or 1-hexamethyleneimino; n is 2 or 3; and z is --O-- or --S--; or a pharmaceutically acceptable salt thereof, for inhibiting restenosis.
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- 2-phenylbenzo[B]furans, process for their manufacture and pharmaceutical preparations containing them
-
The invention relates to new furans and thiophenes with the general Formula 1, STR1 in which R1 and R2 independently of one another denote a hydrogen atom, an alkyl group having 1 to 10 carbon atoms, a benzyl group, a group C(O)R4, where R4 is an alkyl or alkoxy group having 1 to 10 carbon atoms or a phenyl radical, or a carbamoyl group --C(O)NR5 R6, where R5 and R6 independently of one another are a hydrogen atom or an alkyl group having 1 to 10 carbon atoms, and n denotes an integer from 0 to 12 if R3 is a hydrogen atom, or n denotes an integer from 4 to 12 if R3 is an amino group --NR7 R8, where R7 and R8 independently of one another represent a hydrogen atom or an alkyl group having 1 to 10 carbon atoms or R7 and R8 together represent an alkylene group --(CH2)m -- or the group --(CH2)2 -- or R3 denotes an amide group --C(O)NR7 R 8, where R7 and R8 have the abovementioned meanings, or R3 denotes a sulphinyl group --S(O)R3, where R9 is the radical --(CH2)m (CF2)o CF3 and m and o are 2, 3, 4, 5 or 6 and x denotes an oxygen or sulphur atom. These new compounds are strong and selective anti-oestrogens, and have therapeutic applications in the treatment of oestrogen-related illnesses.
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- Treatment of mammary cancer
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Mammary cancers are inhibited by administration of a combination of two drugs. The first compound is 6-hydroxy-2-(4-hydroxyphenyl)-3-[4-(2-pyrrolidinoethoxy)benzoyl]benzo[b]thiophene, and the second compound is tamoxifen.
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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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- 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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