- Direct synthesis of diverse 2-aminobenzo[b]thiophenes via palladium-catalyzed carbon-sulfur bond formation using Na2S2O3 as the sulfur source
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A novel and direct synthesis of various 2-aminobenzo[b]thiophenes has been developed. The reactions were catalyzed by a combination of Pd(dppf)Cl2 and dppf using odorless and cheap Na2S2O3 as the sulfur source. This strategy allowed us to synthesize important 2-aminobenzo[b]thiophene scaffold more efficiently and conveniently.
- Hou, Chuanwei,He, Qian,Yang, Chunhao
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- New HIV-1 reverse transcriptase inhibitors based on a tricyclic benzothiophene scaffold: Synthesis, resolution, and inhibitory activity
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We synthesized, separated into enantiomers, and tested for the HIV-1 reverse transcriptase inhibitory activity a group of analogs of dimethyl-1-(1-piperidynyl)cyclobuta[b][1]benzothiophene-2,2a(7bH)-dicarboxylate (NSC-380292). Absolute configurations of the enantiomers were determined based on absolute X-ray structures and analysis of CD spectra. Within pairs of enantiomers the (R,R)-enantiomer was always much more potent HIV-1 reverse transcriptase inhibitor.
- Krajewski, Krzysztof,Zhang, Yijun,Parrish, Damon,Deschamps, Jeffrey,Roller, Peter P.,Pathak, Vinay K.
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p. 3034 - 3038
(2008/12/21)
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- Synthesis and binding affinities of fluoroalkylated raloxifenes
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Three fluoroalkylated derivatives (1-3) of the selective estrogen receptor modulator (SERM), raloxifene, have been synthesized. The key step in the synthesis is the C-C bond formation of benzo[b]thiophene and a substituted phenyl group (ring C) using a Stille reaction. The in vitro binding affinities of the substituted raloxifenes 1-3 are 45, 60, 89%, respectively, relative to the affinity of estradiol, which is higher than the affinity of raloxifene itself (25%). When labeled with the positron-emitting radionuclide, these compounds might be useful as PET imaging agents for estrogen receptor-positive breast tumors.
- Lee, Kyo Chul,Moon, Byung Seok,Lee, Jae Hak,Chung, Kyoo-Hyun,Katzenellenbogen, John A.,Chi, Dae Yoon
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p. 3649 - 3658
(2007/10/03)
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- Kinetic mechanism for dimerization of an α-thioamide substituted benzyl carbocation in aqueous solution
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The products of reaction of the α-(N,N-dimethylthiocarbamoyl)-4-methoxybenzyl carbocation (1+) intermediate of solvolysis of α-(N,N-dimethylthiocarbamoyl)-4-methoxybenzyl benzoate esters (1-O2CAr) show a strong dependence on solvent. The only product from reaction in 1,1,1,3,3,3-hexafluoro-2-propanoI (HFIP) is 2-dimethylamino-6-methoxybenzothiophene (2) from intramolecular cyclization of 1+. The reaction of 1+ in 50:50 (v/v) methanol-water (I = 0.50, NaClO4) gives mainly the adducts to solvent. In 50:50 (v/v) trifluoroethanol-water (I = 0.50, NaClO4), 1+ partitions between reaction with solvent (ks, 27% yield), cyclization to form 2 (kc, 3% yield) and nucleophilic addition of 2 to 1+ (kalk, 70% yield) to form dimeric product 3. The yield of 3 in 50:50 (v/v) trifluoroethanol-water (I = 0.50, NaClO4) is independent of the leaving group at 1-O2CAr and remains constant as the concentration of the substrate is increased fourfold. These data show that the rate-determining step for dimerization of 1-O2CAr is ionization of substrate to form 1+ and that the products of the reaction are determined by the rate constant ratio for partitioning of 1+ between addition of solvent and cyclization. The rate constant ratios determined for the partitioning of 1+ in 50:50 (v/v) trifluoroethanol-water (I = 0.50, NaClO4) were ks/kc = 0.8 M-1 and kalk/ks = 540 000 M-1.
- Williams, Kathleen B.,Richard, John P.
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p. 701 - 706
(2007/10/03)
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- Benzothiphene derivatives for treating resistant tumors
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This invention provides a series of substituted benzo[b]thiophenes useful in reversing multidrug resistance in a resistant neoplasm. The present invention also provides methods for reversing the multidrug resistance in a resistant neoplasm by treating a mammal in need of said treatment with a substituted benzothiophene. This invention also provides methods for treating neoplasms in a mammal which comprises administering to a mammal in need of this treatment a substituted benzothiophene in combination with an oncolytic agent.
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- How does organic structure determine organic reactivity? Nucleophilic substitution and alkene-forming elimination reactions of α-carbonyl and α-thiocarbonyl substituted benzyl derivatives
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The effect of α-(N,N-dimethylcarbamoyl) and α-(N,N-dimethylthiocarbamoyl) substituents on the rate constants for partitioning of α-substituted 1-(4-methoxyphenyl)ethyl carbocations between nucleophilic addition of 50:50 (v:v) MeOH/H20 (k(s), s-1) and deprotonation by this solvent (k(e), s-1) have been investigated. The data show that these α-amide and α-thioamide substituents result in 80-fold and ≤ 30000-fold decreases, respectively, in k(s) for capture of the 4-methoxybenzyl carbocation by solvent, but that they lead to much smaller changes in k(e), for deprotonation of the corresponding α-substituted 1-(4-methoxyphenyl)ethyl carbocations by solvent. The large effect of the α-thioamide substituent on the partitioning of α-substituted 1-phenylethyl carbocations between formation of the products of solvolysis and elimination is therefore due primarily to the effect of this α-substituent on k(s), for capture of the carbocation by solvent. The results of experimental and computational studies are consistent with the conclusion that the relative magnitude of the rate constants k(s) and k(e) for partitioning of α-substituted 1-phenylethyl carbocations is strongly controlled by the relative thermodynamic stabilities of the neutral products of these reactions.
- Richard, John P.,Lin, Shrong-Shi,Buccigross, Jeanne M.,Amyes, Tina L.
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p. 12603 - 12613
(2007/10/03)
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- DESTABILIZED CARBOCATIONS. NUCLEAR MATNETIC RESONANCE DETECTION AND REACTIVITIES OF ARYL α-THIOFORMAMIDYL CATIONS
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A series of α-aryl and diarylthioformamidyl cations were observed by low-temperature nuclear magnetic resonance spectroscopy.These ions undergo efficient cyclization and deprotonation to give benzothiophenes.
- Ablenas, F. J.,George, B. E.,Maleki, M.,Jain, R.,Hopkinson, A. C.,Lee-Ruff, E.
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p. 1800 - 1803
(2007/10/02)
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