3610-02-4

Usage

Hazard

A poison.

InChI:InChI=1/C8H6OS/c9-7-2-1-3-8-6(7)4-5-10-8/h1-5,9H

Upstream product

• 13414-95-4 4-keto-4,5,6,7-tetrahydrothianaphthene 
• 17402-83-4 benzo[B]thiophen-4-ylamine 
• 74477-43-3 4-Trimethylsiloxy-6,7-dihydrobenzo-thiophen 
• 66241-29-0 Acetic acid 6-oxo-9-thia-bicyclo[3.3.1]nona-3,7-dien-2-yl ester 
• 95-15-8 Benzo[b]thiophene 
• 127491-04-7 4-nitro-benzo[b]thiophen-5-ylamine 
• 915411-13-1 6-bromo-6,7-dihydro-4-benzothio[b]phenone 
• 2513-49-7 4,5,6,7-tetrahydro-4-oxo-5-bromo-benzothiophene 
• 857473-95-1 N-(4-nitro-benzo[b]thiophen-5-yl)-acetamide 
• 18044-91-2 benzo[b]thiophen-5-yl-acetamide 
• 10133-34-3 4-nitrobenzene[b]thiophene 
• 150-90-3 sodium succinate 

Downstream Products

• 82194-96-5 4-hydroxy-2,3-dihydrobenzo[b]thiophene 
• 82194-84-1 2-p-Tolyl-2,3-dihydro-benzo[b]thiophen-4-ol 
• 82194-91-0 3-p-Tolyl-2,3-dihydro-benzo[b]thiophen-4-ol 
• 82194-98-7 4,5-dihydro-2,4-di-p-tolylbenzothiophen-7(6H)-one 
• 3781-90-6 4-methoxybenzo[b]thiophene 
• 82194-83-0 2-Phenyl-2,3-dihydro-benzo[b]thiophen-4-ol 
• 82194-90-9 3-Phenyl-2,3-dihydro-benzo[b]thiophen-4-ol 
• 82194-75-0 4,5-dihydro-2,4-diphenylbenzothiophen-7(6H)-one 
• 214552-42-8 2-(tert-Butyl-dimethyl-silanyl)-6-(2-hydroxy-2-phenyl-ethyl)-4-methoxy-benzo[b]thiophene-5-carboxylic acid diethylamide 
• 693257-90-8 [3-(benzo[b]thiophen-4-yloxy)-5-methyl-hexyl]-benzyl-methyl-amine 
• 34577-05-4 benzo[b]thiophen-4-yl benzoate 
• 193965-82-1 2-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophen-4-yl 4-Fluorobenzoate 
• 325982-57-8 4-[2-(benzo[b]thiophene-4-yloxy)-ethyl]-5-methyl-2-phenyl-oxazole 
• 1191901-07-1 tert-butyl 4-(benzo[b]thiophen-4-yl)piperazine-1-carboxylate 

Relevant academic research and scientific papers

Delineating an alternate convergent synthesis of brexpiprazole: a novel use of commercial 6,7-dihydrobenzo[b]thiophen-4(5H)-one as precursor to an efficacious Buchwald–Hartwig amination step

Abstract: Brexpiprazole – an anti-psychotic drug approved for the treatment of schizophrenia – has been synthesized via an extremely concise and convergent route, which involves in essence two key C–N bond formation (amination) steps that serve to link the piperazine core between the constituent benzo[b]thiophene and 7-butoxyquinolin-2(1H)-one fragments. The highlight of this synthesis is the first amination step, which was effected quite efficaciously by a novel palladium mediated Buchwald–Hartwig coupling between N-Boc-piperazine and the triflate ester of benzo[b]thiophen-4-ol (conveniently prepared in three steps from commercially available 6,7-dihydrobenzo[b]thiophen-4(5H)-one). Indeed, even without an extensive screening of catalysts, ligands and reaction conditions, this amination step could be performed quite efficiently with merely 1?mol% catalyst loading, which cleanly afforded in 87% overall yield 1-(benzo[b]thiophen-4-yl)piperazine—the starting material for the second C–N bond formation and the final step in the synthesis of Brexpiprazole. Graphical Abstract: Synopsis An alternate convergent synthesis of the anti-psychotic drug Brexpiprazole has been described. In particular, a novel palladium catalyzed Buchwald–Hartwig coupling of N-Boc-piperazine with benzo[b]thiophen-4-yl trifluoromethanesulfonate (prepared from commercially available 6,7-dihydrobenzo[b]thiophen-4(5H)-one) has been shown to furnish 1-(benzo[b]thiophen-4-yl)piperazine (a key intermediate in the synthesis of the API) in excellent yield even with 1?mol% catalyst loading. [Figure not available: see fulltext.].

NOVEL TRICYCLIC CALCIUM SENSING RECEPTOR ANTAGONISTS

Novel tricyclic compounds of Formula (I) and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing osteoporosis and similar conditions. The compounds are effective as calcium sensing receptor antagonists. Pharmaceutical compositions and methods of treatment are also included.

NOVEL TRICYCLIC CALCIUM SENSING RECEPTOR ANTAGONISTS FOR THE TREATMENT OF OSTEOPOROSIS

Novel tricyclic compounds of the formula (I): and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing osteoporosis and similar conditions. The compounds are effective as calcium sensing receptor antagonists. Pharmaceutical compositions and methods of treatment are also included.

Toluene dioxygenase-catalyzed cis-dihydroxylation of benzo[b]thiophenes and benzo[b]furans: Synthesis of benzo[b]thiophene 2,3-oxide

Enzymatic cis-dihydroxylation of benzo[b]thiophene, benzo[b]furan and several methyl substituted derivatives was found to occur in both the carbocyclic and heterocyclic rings. Relative and absolute configurations and enantiopurities of the resulting dihydrodiols were determined. Hydrogenation of the alkene bond in carbocyclic cis-dihydrodiols and ring-opening epimerization/reduction reactions of heterocyclic cis/trans-dihydrodiols were also studied. The relatively stable heterocyclic dihydrodiols of benzo[b]thiophene and benzo[b]furan showed a strong preference for the trans configuration in aqueous solutions. The 2,3-dihydrodiol metabolite of benzo[b]thiophene was utilized as a precursor in the chemoenzymatic synthesis of the unstable arene oxide, benzo[b]thiophene 2,3-oxide.

Design and synthesis of pyrrolo[3,2- d ]pyrimidine human epidermal growth factor receptor 2 (HER2)/epidermal growth factor receptor (EGFR) dual inhibitors: Exploration of novel back-pocket binders

To develop novel human epidermal growth factor receptor 2 (HER2)/epidermal growth factor receptor (EGFR) kinase inhibitors, we explored pyrrolo[3,2-d]pyrimidine derivatives bearing bicyclic fused rings designed to fit the back pocket of the HER2/EGFR proteins. Among them, the 1,2-benzisothiazole (42m) ring was selected as a suitable back pocket binder because of its potent HER2/EGFR binding and cell growth inhibitory (GI) activities and pseudoirreversibility (PI) profile as well as good bioavailability (BA). Ultimately, we arrived at our preclinical candidate 51m by optimization of the N-5 side chain to improve CYP inhibition and metabolic stability profiles without a loss of potency (HER2/EGFR inhibitory activity, IC50, 0.98/2.5 nM; and GI activity BT-474 cells, GI50, 2.0 nM). Reflecting the strong in vitro activities, 51m exhibited potent tumor regressive efficacy against both HER2- and EGFR-overexpressing tumor (4-1ST and CAL27) xenograft models in mice at oral doses of 50 mg/kg and 100 mg/kg.

Bacterial dioxygenase- and monooxygenase-catalysed sulfoxidation of benzo[b]thiophenes

Asymmetric heteroatom oxidation of benzo[b]thiophenes to yield the corresponding sulfoxides was catalysed by toluene dioxygenase (TDO), naphthalene dioxygenase (NDO) and styrene monooxygenase (SMO) enzymes present in P. putida mutant and E. coli recombinant whole cells. TDO-catalysed oxidation yielded the relatively unstable benzo[b]thiophene sulfoxide; its dimerization, followed by dehydrogenation, resulted in the isolation of stable tetracyclic sulfoxides as minor products with cis-dihydrodiols being the dominant metabolites. SMO mainly catalysed the formation of enantioenriched benzo[b]thiophene sulfoxide and 2-methyl benzo[b]thiophene sulfoxides which racemized at ambient temperature. The barriers to pyramidal sulfur inversion of 2- and 3-methyl benzo[b]thiophene sulfoxide metabolites, obtained using TDO and NDO as biocatalysts, were found to be ca.: 25-27 kcal mol-1. The absolute configurations of the benzo[b]thiophene sulfoxides were determined by ECD spectroscopy, X-ray crystallography and stereochemical correlation. A site-directed mutant E. coli strain containing an engineered form of NDO, was found to change the regioselectivity toward preferential oxidation of the thiophene ring rather than the benzene ring.

BENZISOXAZOLE COMPOUND

Disclosed is a compound represented by the general formula (I) or a salt thereof: wherein any one of R1, R2 and R3 represents a group represented by the formula: -(CH2)m-NR11R12 (wherein m is 1 or 2; and R11 and R12 independently represent a hydrogen atom or a C1-6 alkyl group or may, together with a nitrogen atom to which R11 and R12 are bound, form a 4- or 5-membered cyclic group); the remaining two or R1, R2 and R3 independently represent a group represented by the formula: -(O)n-R21 (wherein n is 0 or 1; and R21 represents a hydrogen atom, a C1-6 alkyl group, a C2-6 alkenyl group, a C2-6 alkynyl group, or the like); and R4 represents a C1-6 alkyl group which may have a substituent or the like.

ANTI-CANCER AGENTS ANS USES THEREOF

The present invention is in the area of novel compounds and salts thereof, their syntheses, and their use as anti-cancer agents. The compounds include compounds of Formula (I): and solvates, hydrates and pharmaceutically-acceptable salts thereof, wherein A1 is N or CR1; A3 is N or CR3; A5 is N or CR5; R1, R3 R6 and L are defined in the specification; n is 0 or 1; and X is an optionally-substituted aryl group having 6- 10 carbons in the ring portion, an optionally-substituted 6- membered heteroaryl group having 1- 3 nitrogen atoms in the ring portion, an optionally-substituted 5- membered heteroaryl group having 0- 4 nitrogen atoms in the ring portion and optionally having 1 sulfur atom or 1 oxygen atom in the ring portion, or an optionally-substituted heteroaryl group in which a 6- membered ring is fused either to a 5- membered ring or to a 6- membered ring, wherein in each case 1, 2, 3 or 4 ring atoms are heteroatoms independently selected from nitrogen, oxygen and sulfur. They are effective against a broad range of cancers, especially leukemia, prostate, non-small cell lung and colon. They are additionally useful in the treatment of proliferative retinopathies such as diabetic neuropathy and macular degeneration.

[4-(Benzo[B]Thiophen-2-Yl) Pyrimidin-2-Yl]-Amine Derivatives As Ikk-Beta Inhibitors For The Treatment Of Cancer And Inflammatory Diseases

The present invention provides compounds of Formula I: useful in the treatment of cancer and inflammatory diseases.

9-AZABICYCLO [3 . 3 . 1] NONANE DERIVATIVES AS MONOAMINE REUPTAKE INHIBITORS

The present invention relates to a 9-azabicyclo[3.3.1]nonane derivative of formula (I), wherein R1 is H or C1-5alkyl; X is O or NR2, wherein R2 is H, C1-5alkyl or C2-5acyl and Ar is C6-10aryl or a 5-10 membered heteroaryl ring system, both being optionally substituted with one to three of R3-R5 independently selected from halogen, C1-5alkyl, C1-5alkoxy, C3-6cycloalkyl, C2-5alkenyl, C2-5alkynyl, CN, NO2, hydroxy, phenyl, phenoxy and phenylC1-2alkoxy, wherein said C1-5alkyl and C1-5alkoxy are optionally substituted with one to three halogens and wherein said phenyl, phenoxy and phenylC1-2alkoxy are optionally substituted with one to three substituents independently selected from halogen and methyl or two of R3-R5 at adjacent positions together form a methylenedioxy or propylene unit, with the proviso that the compounds exo-9-methyl-3-phenoxy-9-azabicyclo[3.3.1]nonane and N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-1H indazole-5-amine are excluded, or a pharmaceutically acceptable salt or solvate thereof. The invention also relates to pharmaceutical compositions comprising said 9-azabicyclo[3.3.1]nonane derivatives and to their use in therapy.