- Design, synthesis, and biological activity evaluation of 2-(benzo[b]thiophen-2-yl)-4-phenyl-4,5-dihydrooxazole derivatives as broad-spectrum antifungal agents
-
To discover antifungal compounds with broad-spectrum and stable metabolism, a series of 2-(benzo[b]thiophen-2-yl)-4-phenyl-4,5-dihydrooxazole derivatives was designed and synthesized. Compounds A30-A34 exhibited excellent broad-spectrum antifungal activity against Candida albicans with MIC values in the range of 0.03–0.5 μg/mL, and against Cryptococcus neoformans and Aspergillus fumigatus with MIC values in the range of 0.25–2 μg/mL. In addition, compounds A31 and A33 showed high metabolic stability in human liver microsomes in vitro, with the half-life of 80.5 min and 69.4 min, respectively. Moreover, compounds A31 and A33 showed weak or almost no inhibitory effect on the CYP3A4 and CYP2D6. The pharmacokinetic evaluation in SD rats showed that compound A31 had suitable pharmacokinetic properties and was worthy of further study.
- Zhao, Liyu,Sun, Yin,Yin, Wenbo,Tian, Linfeng,Sun, Nannan,Zheng, Yang,Zhang, Chu,Zhao, Shizhen,Su, Xin,Zhao, Dongmei,Cheng, Maosheng
-
-
- Milled Dry Ice as a C1 Source for the Carboxylation of Aryl Halides
-
The use of carbon dioxide as a C1 chemical feedstock remains an active field of research. Here we showcase the use of milled dry ice as a method to promote the availability of CO 2in a reaction solution, permitting practical synthesis of arylcarboxylic acids. Notably, the use of milled dry ice produces marked increases in yields relative to those obtained with gaseous CO 2, as previously reported in the literature.
- O'Brien, Connor J.,Nicewicz, David A.
-
supporting information
p. 814 - 816
(2021/03/01)
-
- Oxidation of Primary Alcohols and Aldehydes to Carboxylic Acids via Hydrogen Atom Transfer
-
The oxidation of primary alcohols and aldehydes to the corresponding carboxylic acids is a fundamental reaction in organic synthesis. In this paper, we report a new chemoselective process for the oxidation of primary alcohols and aldehydes. This metal-free reaction features a new oxidant, an easy to handle procedure, high isolated yields, and good to excellent functional group tolerance even in the presence of vulnerable secondary alcohols and tert-butanesulfinamides.
- Tan, Wen-Yun,Lu, Yi,Zhao, Jing-Feng,Chen, Wen,Zhang, Hongbin
-
supporting information
p. 6648 - 6653
(2021/09/08)
-
- Photo-induced deep aerobic oxidation of alkyl aromatics
-
Oxidation is a major chemical process to produce oxygenated chemicals in both nature and the chemical industry. Presently, the industrial manufacture of benzoic acids and benzene polycarboxylic acids (BPCAs) is mainly based on the deep oxidation of polyalkyl benzene, which is somewhat suffering from environmental and economical disadvantage due to the formation of ozone-depleting MeBr and corrosion hazards of production equipment. In this report, photo-induced deep aerobic oxidation of (poly)alkyl benzene to benzene (poly)carboxylic acids was developed. CeCl3 was proved to be an efficient HAT (hydrogen atom transfer) catalyst in the presence of alcohol as both hydrogen and electron shuttle. Dioxygen (O2) was found as a sole terminal oxidant. In most cases, pure products were easily isolated by simple filtration, implying large-scale implementation advantages. The reaction provides an ideal protocol to produce valuable fine chemicals from naturally abundant petroleum feedstocks. [Figure not available: see fulltext.].
- Wang, Chang-Cheng,Zhang, Guo-Xiang,Zuo, Zhi-Wei,Zeng, Rong,Zhai, Dan-Dan,Liu, Feng,Shi, Zhang-Jie
-
p. 1487 - 1492
(2021/07/10)
-
- Design, synthesis, and biological evaluation of benzo[b]thiophene 1,1-dioxide derivatives as potent STAT3 inhibitors
-
As a member of the signal transducer and activator of transcription (STAT) family, STAT3 plays a critical role in several biological pathways such as cell proliferation, migration, survival, and differentiation. Due to abnormal continuous activation in tumors, inhibition of STAT3 has emerged as an attractive approach for the treatment of various cancer cells. Herein, we report a series of novel STAT3 inhibitors based on benzo[b]thiophene 1,1-dioxide scaffold and evaluated their anticancer potency. Among them, compound 8b exhibited the best activity against cancer cells. Compound 8b induced apoptosis and blocked the cell cycle. Meanwhile, 8b reduced intracellular ROS content and caused the loss of mitochondrial membrane potential. Further research revealed that 8b significantly blocked STAT3 phosphorylation and STAT3-dependent dual-luciferase reporter gene experiments showed that compound 8b has a marked inhibition of STAT3-mediated Firefly luciferase activity. Molecular modeling studies revealed compound 8b occupied the pocket well with the SH2 domain in a favorable conformation.
- Li, Wen-Zhen,Xi, Hui-Zhi,Wang, Yi-Jie,Ma, Hong-Bo,Cheng, Zhi-Qiang,Yang, Yu,Wu, Meng-Ling,Liu, Ting-Mei,Yang, Wen,Wang, Qin,Liao, Meng-Ya,Xia, Yong,Zhang, Yi-Wen
-
p. 835 - 849
(2021/09/02)
-
- 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)
-
- Light and oxygen-enabled sodium trifluoromethanesulfinate-mediated selective oxidation of C-H bonds
-
Visible light-induced organic reactions are important chemical transformations in organic chemistry, and their efficiency highly depends on suitable photocatalysts. However, the commonly used photocatalysts are precious transition-metal complexes and elaborate organic dyes, which hamper large-scale production due to high cost. Here, for the first time, we report a novel strategy: light and oxygen-enabled sodium trifluoromethanesulfinate-mediated selective oxidation of C-H bonds, allowing high-value-added aromatic ketones and carboxylic acids to be easily prepared in high-to-excellent yields using readily available alkyl arenes, methyl arenes and aldehydes as materials. The mechanistic investigations showed that the treatment of inexpensive and readily available sodium trifluoromethanesulfinate with oxygen under irradiation of light could in situ form a pentacoordinate sulfide intermediate as an efficient photosensitizer. The method represents a highly efficient, economical and environmentally friendly strategy, and the light and oxygen-enabled sodium trifluoromethanesulfinate photocatalytic system represents a breakthrough in photochemistry. This journal is
- Fu, Hua,Liu, Can,Liu, Yong,Yang, Haijun,Zhu, Xianjin
-
supporting information
p. 4357 - 4363
(2020/07/14)
-
- Lithium-Free Synthesis of Sodium 2,2,6,6-Tetramethylpiperidide and Its Synthetic Applications
-
Lithium-free synthetic methods for sodium 2,2,6,6-tetramethylpiperide (NaTMP) have been developed using sodium dispersion as a sole sodium source. The prepared NaTMP was used as a Br?nsted base, that exhibited some differences in reactivities from LiTMP. (Figure presented.).
- Asako, Sobi,Kodera, Masato,Nakajima, Hirotaka,Takai, Kazuhiko
-
supporting information
p. 3120 - 3123
(2019/05/22)
-
- METHOD FOR SYNTHESIZING SODIUM 2,2,6,6-TETRAMETHYLPIPERIDIDES
-
There is a demand for the development of a technique according to which sodium 2,2,6,6-tetramethylpiperidides (Na-TMPs) can be economically and efficiently synthesized through simple operations including a small number of steps under mild conditions in a short period of time. Also, there is a demand for the development of a technique according to which high-quality Na-TMPs that do not contain lithium or lithium compounds such as Li-TMP can be synthesized. The method for synthesizing sodium 2,2,6,6-tetramethylpiperidides includes a step of obtaining sodium 2,2,6,6-tetramethylpiperidides by reacting, in a reaction solvent, 2,2,6,6-tetramethylpiperidines with a dispersion product obtained by dispersing sodium in a dispersion solvent or an organosodium compound having an aromatic ring obtained through a reaction with a dispersion product obtained by dispersing sodium in a dispersion solvent.
- -
-
Paragraph 0127; 0130; 0131; 0138; 0139
(2019/12/10)
-
- Design, synthesis and evaluation of benzoheterocycle analogues as potent antifungal agents targeting CYP51
-
To further enhance the anti-Aspergillus efficacy of our previously discovered antifungal lead compound 1, a series of benzoheterocycle analogues were designed, synthesized and evaluated for their in vitro antifungal activity. The most promising compounds 13s and 14a exhibited excellent antifungal activity against C. albicans, C. neoformans, A. fumigatus and fluconazole-resistant C. albicans strains, that was superior or comparable to those of the reference drugs fluconazole and voriconazole. GC–MS analyses suggested that the novel compound 13s might have a similar mechanism to fluconazole by inhibiting fungal lanosterol 14α-demethylase (CYP51). Furthermore, compounds 13s and 14a exhibited low inhibition profiles for various human cytochrome P450 isoforms as well as excellent blood plasma stability.
- Zhao, Shizhen,Wei, Peng,Wu, Mengya,Zhang, Xiangqian,Zhao, Liyu,Jiang, Xiaolin,Hao, Chenzhou,Su, Xin,Zhao, Dongmei,Cheng, Maosheng
-
p. 3242 - 3253
(2018/05/23)
-
- A biocatalytic method for the chemoselective aerobic oxidation of aldehydes to carboxylic acids
-
Herein, we present a study on the oxidation of aldehydes to carboxylic acids using three recombinant aldehyde dehydrogenases (ALDHs). The ALDHs were used in purified form with a nicotinamide oxidase (NOx), which recycles the catalytic NAD+ at the expense of dioxygen (air at atmospheric pressure). The reaction was studied also with lyophilised whole cell as well as resting cell biocatalysts for more convenient practical application. The optimised biocatalytic oxidation runs in phosphate buffer at pH 8.5 and at 40 °C. From a set of sixty-one aliphatic, aryl-Aliphatic, benzylic, hetero-Aromatic and bicyclic aldehydes, fifty were converted with elevated yield (up to >99%). The exceptions were a few ortho-substituted benzaldehydes, bicyclic heteroaromatic aldehydes and 2-phenylpropanal. In all cases, the expected carboxylic acid was shown to be the only product (>99% chemoselectivity). Other oxidisable functionalities within the same molecule (e.g. hydroxyl, alkene, and heteroaromatic nitrogen or sulphur atoms) remained untouched. The reaction was scaled for the oxidation of 5-(hydroxymethyl)furfural (2 g), a bio-based starting material, to afford 5-(hydroxymethyl)furoic acid in 61% isolated yield. The new biocatalytic method avoids the use of toxic or unsafe oxidants, strong acids or bases, or undesired solvents. It shows applicability across a wide range of substrates, and retains perfect chemoselectivity. Alternative oxidisable groups were not converted, and other classical side-reactions (e.g. halogenation of unsaturated functionalities, Dakin-Type oxidation) did not occur. In comparison to other established enzymatic methods such as the use of oxidases (where the concomitant oxidation of alcohols and aldehydes is common), ALDHs offer greatly improved selectivity.
- Knaus, Tanja,Tseliou, Vasilis,Humphreys, Luke D.,Scrutton, Nigel S.,Mutti, Francesco G.
-
supporting information
p. 3931 - 3943
(2018/09/11)
-
- Accepting the Invitation to Open Innovation in Malaria Drug Discovery: Synthesis, Biological Evaluation, and Investigation on the Structure-Activity Relationships of Benzo[b]thiophene-2-carboxamides as Antimalarial Agents
-
Malaria eradication is a global health priority, but current therapies are not always suitable for providing a radical cure. Artemisinin has paved the way for the current malaria treatment, the so-called Artemisinin-based Combination Therapy (ACT). However, with the detection of resistance to ACT, innovative compounds active against multiple parasite species and at multiple life stages are needed. GlaxoSmithKline has recently disclosed the results of a phenotypic screening of an internal library, publishing a collection of 400 antimalarial chemotypes, termed the “Malaria Box”. After analysis of the data set, we have carried out a medicinal chemistry campaign in order to define the structure-activity relationships for one of the released compounds, which embodies a benzothiophene-2-carboxamide core. Thirty-five compounds were prepared, and a description of the structural features responsible for the in vitro activity against different strains of P. falciparum, the toxicity, and the metabolic stability is herein reported.
- Pieroni, Marco,Azzali, Elisa,Basilico, Nicoletta,Parapini, Silvia,Zolkiewski, Michal,Beato, Claudia,Annunziato, Giannamaria,Bruno, Agostino,Vacondio, Federica,Costantino, Gabriele
-
p. 1959 - 1970
(2017/03/17)
-
- Synthesis and Antitubercular Activity of New Benzo[b]thiophenes
-
In vitro and ex vivo efficacies of four series of benzo[b]thiophene-2-carboxylic acid derivatives were studied against Mycobacterium tuberculosis H37Ra (MTB). Benzo[b]thiophenes were also tested in vitro against multidrug resistant Mycobacterium tuberculosis H37Ra (MDR-MTB), and 7b was found to be highly active against A- and D-MDR-MTB/MTB (MIC ranges 2.73-22.86 μg/mL). The activity of all benzo[b]thiophenes against M. bovis BCG (BCG) was also assessed grown under aerobic and under conditions of oxygen depletion. Compounds 8c and 8g showed significant activity with MICs of 0.60 and 0.61 μg/mL against dormant BCG. The low cytotoxicity and high selectivity index data against human cancer cell lines, HeLa, Panc-1, and THP-1 indicate the potential importance of the development of benzo[b]thiophene-based 1,3-diketones and flavones as lead candidates to treat mycobacterial infections. Molecular docking studies into the active site of DprE1 (Decaprenylphosphoryl-β-d-ribose-2′-epimerase) enzyme revealed a similar binding mode to native ligand in the crystal structure thereby helping to understand the ligand-protein interactions and establish a structural basis for inhibition of MTB. In summary, its good activity in in vitro and ex vivo model, as well as its activity against multidrug-resistant M. tuberculosis H37Ra in a potentially latent state, makes 7b an attractive drug candidate for the therapy of tuberculosis.
- Mahajan, Pravin S.,Nikam, Mukesh D.,Nawale, Laxman U.,Khedkar, Vijay M.,Sarkar, Dhiman,Gill, Charansingh H.
-
p. 751 - 756
(2016/08/24)
-
- Benzo[b]thiophene-2-carboxamide derivatives as potent urotensin-II receptor antagonists
-
Members of a series of benzo[b]thiophene-2-carboxamide derivatives, possessing an N-(1-(3-bromo-4-(piperidin-4-yloxy)benzyl)piperidin-4-yl) group, were synthesized and evaluated as urotensin-II receptor antagonists. The results show that these substances have potent UT binding affinities. Observations made in a systematic SAR investigation of the effects of a variety of substituents (R1and R2) at the 5- and 6-positions in the benzo[b]thiophene-2-carboxamide moiety on UT binding affinities led to identification of the 5-cyano analog 7f as a highly potent UT antagonist with an IC50value of 25?nM. Despite having a good metabolic stability, 7f is a potent inhibitor of CYP isozyme and displays an unsuitable PK profile.
- Lim, Chae Jo,Woo, Seong Eun,Ko, Su Ik,Lee, Byung Ho,Oh, Kwang-Seok,Yi, Kyu Yang
-
p. 4684 - 4686
(2016/09/13)
-
- Preparation method for benzothiophene-2-carboxylic acid
-
The invention discloses a preparation method for benzothiophene-2-carboxylic acid. In a high pressure vessel, 3-mercapto coumarin is used as a raw material, and tetrabutylammonium bromide is used as a catalyst to be subjected to a reaction in alkali liquor; the pressure inside the high pressure vessel is adjusted to be 0.8-1.2 Mpa, and then the high pressure vessel is heated to 130-160 DEG C for a reaction for 7-10 h; the catalyst is 2-12.5 mol% of the raw material, and the alkali liquor is 1.5-3.6 mol times of the raw material; after the reaction is finished, cooling is performed to the room temperature, concentrated hydrochloric acid is added for acidification till the pH value of the reaction products is 3-4, and filtering and drying are performed to obtain the benzothiophene-2-carboxylic acid.
- -
-
Paragraph 0025; 0026
(2017/01/17)
-
- Copper-catalyzed formal c-h carboxylation of aromatic compounds with carbon dioxide through arylaluminum intermediates
-
The C-H bond carboxylation of various aromatic compounds with CO2 was achieved by the deprotonative alumination with a mixed alkyl amido lithium aluminate compound iBu3Al(TMP)Li followed by the NHC-copper-catalyzed carboxylation of the resulting arylaluminum species, which afforded the corresponding carboxylation products in high yield and high selectivity. In addition to benzene derivatives, heteroarenes such as benzofuran, benzothiophene, and indole derivatives are also suitable substrates. Functional groups such as Cl, Br, I, vinyl, amide, and CN could survive the reaction conditions. Some key reaction intermediates such as the copper aryl and isobutyl complexes and their carboxylation products were isolated and structurally characterized by X-ray crystallographic analyses, thus offering important information on the reaction mechanism.
- Ueno, Atsushi,Takimoto, Masanori,Wylie,Nishiura, Masayoshi,Ikariya, Takao,Hou, Zhaomin
-
supporting information
p. 1010 - 1016
(2015/03/31)
-
- Amyl nitrite-mediated conversion of aromatic and heteroaromatic primary amides to carboxylic acids
-
A series of aromatic and heteroaromatic primary amides were converted directly to carboxylic acids by heating with amyl nitrite in acetic acid. Most conversions proceeded to give reasonable to excellent yields on a range of substrates containing various functional groups. This reagent system is thus applicable for the direct hydrolysis of a range of different primary carboxamides. The reaction with a phenolic aromatic substrate afforded two alternative nitration products as major outcomes, evidencing alternative reaction pathways resulting from the free phenolic OH.
- Potter, Garrett T.,Jayson, Gordon C.,Miller, Gavin J.,Gardiner, John M.
-
supporting information
p. 5153 - 5156
(2015/08/19)
-
- Efficient and convenient oxidation of aldehydes and ketones to carboxylic acids and esters with H2O2 catalyzed by Co4HP2Mo15V3O62 in ionic liquid [TEBSA][BF4]
-
A simple, efficient, and eco-friendly procedure for the oxidation of aldehydes and ketones to carboxylic acids and esters with H2O2 catalyzed by Co4HP2Mo15V3O62 in ionic liquid [TEBSA][BF4] has been developed. This atom-economical protocol affords the target products in good to high yields. The products can be separated by a simple extraction with organic solvent, and the catalytic system can be recycled and reused without loss of catalytic activity. Additionally, the possible mechanism of oxidation in the catalytic system is proposed. This journal is
- Hu, Yu-Lin,Li, De-Jiang,Li, Dong-Sheng
-
p. 24936 - 24943
(2015/03/30)
-
- Copper nanoparticles on dichromium trioxide: A highly efficient catalyst from copper chromium hydrotalcite for oxidant-free dehydrogenation of alcohols
-
Stable copper(0) nanoparticles supported on chromium (Cu(0)/Cr2O3) are prepared from the composite precursor copper chromium hydrotalcite. The resulting Cu(0)/Cr2O3 catalyst is first used in the selective dehydrogenation of alcohols to aldehydes. More impressively, these dehydrogenations are performed without oxidants and yields of products are high. The stability of Cu(0)/Cr2O3 is also assessed by studying its recoverability and reusability for up to five cycles.
- Zhu, Yaoqin,Shen, Mengnan,Xia, Yonggen,Lu, Ming
-
p. 152 - 156
(2015/03/30)
-
- Potassium-alkyl magnesiates: Synthesis, structures and Mg-H exchange applications of aromatic and heterocyclic substrates
-
Using structurally well-defined dipotassium-tetra(alkyl)magnesiates, a new straightforward methodology to promote regioselective Mg-H exchange reactions of a wide range of aromatic and heteroaromatic substrates is disclosed. Contacted ion pair intermediates are likely to be involved, with K being the key to facilitate the magnesiation processes. This journal is
- Baillie, Sharon E.,Bluemke, Tobias D.,Clegg, William,Kennedy, Alan R.,Klett, Jan,Russo, Luca,De Tullio, Marco,Hevia, Eva
-
supporting information
p. 12859 - 12862
(2014/12/11)
-
- Flash carboxylation: Fast lithiation-carboxylation sequence at room temperature in continuous flow
-
A method for the direct lithiation of terminal alkynes and heterocycles with subsequent carboxylation in a continuous flow format was developed. This method provides carboxylic acids at ambient conditions within less than five seconds with only little excess of the organometallic base and CO2. This journal is the Partner Organisations 2014.
- Pieber, Bartholomaeus,Glasnov, Toma,Kappe
-
p. 13430 - 13433
(2014/04/03)
-
- Oxidation of primary and secondary alcohols to the corresponding carbonyl compounds with molecular oxygen using 1,1-diphenyl-2-picrylhydrazyl and WO 3/Al2O3 as catalysts
-
The oxidation of primary and secondary alcohols to their corresponding carbonyl compounds proceeds with high efficiency under molecular oxygen in the presence of 1,1-diphenyl-2-picrylhydrazyl (DPPH) and tungsten oxide/alumina (WO3/Al2O3). The method is environmentally benign, because the reaction requires only molecular oxygen as the terminal oxidant and gives water as a side product. Various aromatic, alicyclic, and aliphatic alcohols can be converted to their corresponding carbonyl compounds in excellent yields. It is noteworthy that the oxidative transformation of the alcohols proceeds chemoselectively in the presence of other functional groups. In addition, a plausible catalytic pathway is proposed.
- Zhu, Yaoqin,Xu, Jian,Lu, Ming
-
-
- Investigation on the one-step preparation of 2-substituted benzo[B]thiophenes
-
A convenient and efficient synthesis of 2-substituted benzo[b]thiophenes is described. This one-step reaction of alkylthiobenzaldehyde and activated electrophiles proceeded smoothly in toluene at 120 °C with magnesium oxide as a catalyst. The target 2-sub
- Zhao, Qian,Qian, Chao,Chen, Xin-Zhi
-
p. 873 - 878
(2013/08/23)
-
- Copper(I)-catalyzed carboxylation of aryl- and alkenylboronic esters
-
(Chemical Equation Presented) The copper(I)-catalyzed carboxylation reaction of aryl- and alkenylboronic esters proceeded smoothly under CO 2 to give the corresponding carboxylic acid in good yield. This reaction showed wide generality with higher functional group tolerance compared to the corresponding Rh(I)-catalyzed reaction.
- Takaya, Jun,Tadami, Satoshi,Ukai, Kazutoshi,Iwasawa, Nobuharu
-
supporting information; experimental part
p. 2697 - 2700
(2009/05/26)
-
- Solvent-free microwave synthesis of 3-(4-benzo[b]-thiophene-2-carbonyl)-1-piperazinyl-1-benzo[b]thiophen-2-YL-1-propanones. New hetero bis-ligands with potential 5-HT1A serotonergic activity
-
A novel series of 2-benzothiophenealkylpiperazine derivatives 11 (a-d) with potential affinity at 5-HT1A serotonin receptors have been synthesized via solvent-free, microwave-promoted Michael addition of benzo[b]thiophene piperazine derivatives 6(a-c) to substituted benzo[b]thiophen-2-yl propenones 10(b,c).
- Pessoa-Mahana, Hernan,Kosche C., Johann,Ron H., Nadia,Recabarren-Gajardo, Gonzalo,Saitz B., Claudio,Araya-Maturana, Ramiro,Pessoa-Mahana, C. David
-
experimental part
p. 1913 - 1929
(2009/04/06)
-
- New 2-substituted 1,2,3,4-tetrahydrobenzofuro[3,2-c]pyridine having highly active and potent central α2-antagonistic activity as potential antidepressants
-
The synthesis and biological activity of a series of benzofuro[3,2- c]pyridines and a benzothieno[3,2-c]pyridine are described. These compounds exhibit high affinity for the α2-adrenoceptor, with high selectivity versus the α1-receptor. Compound 1 also shows potent in vivo central activity and has been selected for further biological and clinical evaluation.
- Kennis, Ludo E.J.,Bischoff, Francois P.,Mertens, Carolus J.,Love, Christopher J.,Van den Keybus, Frans A.F.,Pieters, Serge,Braeken, Mirielle,Megens, Anton A.H.P.,Leysen, Josee E.
-
-
- Process for synthesizing substituted 2-benzo [b]thiophenecarboxylic acids and salts thereof
-
A process for the preparation of a substituted 2-benzo[b]thiophenecarboxylic acid compound or an alkali metal salt thereof, which comprises reacting a halobenzoyl derivative with mercaptoacetic acid in the presence of an alkali metal hydroxide and water. Substituted 2-benzo[b]thiophenecarboxylic acid compounds and alkali metal salts thereof are useful as intermediates for pharmaceuticals, agricultural chemicals, material preservatives, and the like.
- -
-
-
- Degradation of the petroleum component's monomethylbenzothiophenes on exposure to light
-
The photochemical degradation of monomethylated benzo[b]thiophenes in aqueous solution was studied to elucidate the fate of crude oil components after an oil spill. One principal reaction pathway involves oxidation of the methyl group(s) to the carboxylic
- Bobinger, Stefan,Andersson, Jan T.
-
p. 2569 - 2579
(2007/10/03)
-
- Heteroaromatic analogs of 1-[2-(diphenylmethoxy)ethyl]- and 1-[2- [bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazines (GBR 12935 and GBR 12909) as high-affinity dopamine reuptake inhibitors
-
A new series of heteroaromatic GBR 12935 [1-[2-(diphenylmethoxy)ethyl]- 4-(3-phenylpropyl)-piperazine] (1) and GBR 12909 [1-[2-[bis(4- fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)-piperazine] (2) analogs was synthesized and evaluated as dopamine transpo
- Matecka, Dorota,Lewis, David,Rothman, Richard B.,Dersch, Christina M.,Wojnicki, Francis H. E.,Glowa, John R.,DeVries, A. Courtney,Pert, Agu,Rice, Kenner C.
-
p. 705 - 716
(2007/10/03)
-
- Process for production of 2-substituted benzo[b]thiophene
-
The present invention provides a process for producing a 2-substituted benzo[b]thiophene, which is characterized by reacting a substituted or unsubstituted 2-halogenobenzaldehyde with sulfur and a compound represented by general formula (1) (wherein M represents an alkali metal; i represents an integer of 0 or 1; j represents an integer of 1 or more; and k represents an integer of 1-2 with a proviso that i+k=2), or with a compound of general formula (1) wherein j is 2 or more, in the presence of an aprotic polar solvent, and then reacting the reaction mixture with a compound represented by general formula (2) (wherein X represents a halogen atom; and R represents an acyl group, a substituted or unsubstituted alkoxycarbonyl group, a substituted or unsubstituted arylcarbonyl group or a cyano group) to give rise to intramolecular ring closure. The present process uses no unstable raw materials; enables production of an intended product in a simple operation at a high yield; and is very effective as a process for industrial production of 2-substituted benzo[b]thiophene.
- -
-
-
- A New Indirect Application of Aggregative Activation: Synthesis of Esters by Cobalt-Catalyzed Carbonylation of Aryl, Heterocyclic, and Vinyl Halides under Atmospheric Pressure
-
Sun lamp illuminated alkoxycarbonylation of aryl, heteroaryl, and vinyl halides was performed under atmospheric pressure of CO in the presence of a cobalt catalyst in situ generated from Co(OAc)2.Illunination through a Pyrex flask was sufficient to catalyze the reaction.This process avoids the use of Co2(CO)8 and excess CH3I, which were required in the earlier procedure.A SRN1 mechanism is proposed.
- Marchal, Joel,Bodiguel, Jacques,Fort, Yves,Caubere, Paul
-
p. 8336 - 8340
(2007/10/02)
-
- Processes for producing 2-substituted benzo[B]thiophene
-
A 2-alkylthiobenzaldehyde of general formula (I) is reacted with a halo compound of general formula (II) to produce a 2-substituted benzo[b]thiophene of general formula (III): STR1 wherein R1 means an alkyl group of 1 to 4 carbon atoms, wherein X1 means Cl or Br; Y means --CO2 H, --CO2 R2, --COR2, --CONH2 or --CN; R2 means an alkyl group of 1 to 4 carbon atoms, STR2 wherein Y is as defined above. The process of this invention is of great economic and industrial value, for 2-acetylbenzo[b]thiophene and 2-benzo[b]thiophenecarboxylic acid, which are important intermediates for drugs and agricultural chemicals among others, can be obtained in a simple manner, easily and in high yield.
- -
-
-
- Benzothiophene-2-carboxamide S,S-dioxides and use
-
New compounds of the formula (I) STR1 in which R1 -R6 have the meanings given in the description, their preparation and use in plant protection, the protection of materials and in the field of human and veterinary medicine. Formula (
- -
-
-
- Benzothiophenes and benzofurans and antiallergic use thereof
-
Novel benzothiophene and benzofuran derivatives having antiallergic activity are described as well as a method of manufacture, pharmaceutical compositions, and methods of use therefor. The disclosure describes the use of derivatives for prevention of the release of mediators including histamine and leukotrienes from basophils and mast cells, and prevent respiratory burst in neutrophils providing activity useful in cardiovascular disorders as well as in antiinflammatory, psoriasis, and antimigraine treatment.
- -
-
-
- A DIRECT SYNTHESIS OF BENZYLTHIOPHENE-3-CARBOXYLIC ACID FROM BENZOTHIOPHENE
-
The direct synthesis of benzothiophene-3-carboxylic acid from benzothiophene utilizing Friedel-Crafts acylation with trichloroacetyl chloride, followed by basic hydrolysis is presented.
- Bonjouklian, R.
-
p. 711 - 714
(2007/10/02)
-
