6774-43-2Relevant academic research and scientific papers
Diels-Alder/Ene Reactivities of 2-(1′-Cycloalkenyl)thiophenes and 2-(1′-Cycloalkenyl)benzo[ b]thiophenes with N-Phenylmaleimides: Role of Cycloalkene Ring Size on Benzothiophene and Dibenzothiophene Product Distributions
Noland, Wayland E.,Kumar, Honnaiah Vijay,Reddi, Yernaidu,Cramer, Christopher J.,Novikov, Alexei V.,Kim, Hyejin,Zhu, Yumeng,Chin, Yoke Ching,Zhou, Yuqi,Radakovic, Predrag,Uprety, Anjola,Xie, Jun,Flick, Grant C.
, p. 5265 - 5287 (2020/05/18)
Scaffolds of thiophene and benzothiophene are the important class of bioactive compounds found abundant in nature. The Diels-Alder reactions of 2-(1′-cycloalkenyl)thiophenes and 2-(1′-cycloalkenyl)benzo[b]thiophenes having the alkene groups present in five-, six-, seven-, eight-, and twelve-membered rings with substituted N-phenylmaleimides are characterized. The size of the cycloalkene rings plays a critical role in dictating the product distributions of expected and isomerized Diels-Alder adducts. 2D NMR studies indicate that the isolated isomers for 2-(1′-cycloalkenyl)thiophenes having five-, six-, and seven-membered rings are aromatized benzothiophene products, whereas eight- and twelve-membered rings are un-rearranged adducts. In addition, the product of subsequent ene-reaction with the N-phenylmaleimide is isolated for the five- and six-membered ring cases. Interestingly, in the 2-(1′-cycloalkenyl)benzo[b]thiophene having five-, six-, seven-, eight-, and twelve-membered rings, the un-rearranged dibenzothiophene Diels-Alder adduct is isolated in every instance. Molecular mechanics and density functional theory (M06-2X and PBE0-D3) calculations are performed to understand the differential reactivity of the various dienes for both the initial Diels-Alder reaction and a possible, subsequent ene reaction.
Improved Inhibitors of Trypanothione Reductase by Combination of Motifs: Synthesis, Inhibitory Potency, Binding Mode, and Antiprotozoal Activities
Eberle, Christian,Lauber, Birgit Sophia,Fankhauser, Daniel,Kaiser, Marcel,Brun, Reto,Krauth-Siegel, R. Luise,Diederich, Francois
scheme or table, p. 292 - 301 (2012/01/11)
Trypanothione reductase (TR) is an essential enzyme in the trypanothione-based redox metabolism of trypanosomatid parasites. This system is absent in humans and, therefore, offers a promising target for the development of selective new drugs against Afric
1-[1-(2-Benzo[b]thiopheneyl)cyclohexyl]piperidine hydrochloride (BTCP) yields two active primary metabolites in vitro: Synthesis, identification from rat liver microsome extracts, and affinity for the neuronal dopamine transporter
Deleuze-Masquefa, Carine,Michaud, Martine,Vignon, Jacques,Kamenka, Jean-Marc
, p. 4019 - 4025 (2007/10/03)
1-[1-(2-Benzo[b]thiopheneyl)cyclohexyl]piperidine hydrochloride (BTCP, 1) and cocaine bind to the neuronal dopamine transporter to inhibit dopamine (DA) reuptake. However, on chronic administration, cocaine produces sensitization, but 1 produces tolerance
PCP receptor and dopamine uptake sites are discriminated by chiral TCP and BTCP derivatives of opposite configuration
Coderc, E.,Cerruti, P.,Vignon, J.,Rouayrenc, J. F.,Kamenka, J. M.
, p. 463 - 470 (2007/10/02)
3-Methylpiperidine derivatives of 1-piperidine (TCP) and 1-thiophenyl)cyclohexyl>piperidine (BTCP) were obtained in their racemic and homochiral forms.They have been tested for their affinity for the K receptor label
Synthesis and Biological Evaluation of 1-thienyl)cyclohexyl>piperidine Homologues at Dopamine-Uptake and Phencyclidine- and ?-Binding Sites
He, Xiao-shu,Raymon, Lionel P.,Mattson, Mariena V.,Eldefrawi, Mohyee E.,Costa, Brian R. de
, p. 1188 - 1193 (2007/10/02)
Piperidine and cyclohexyl ring homologues of the high-affinity dopamine (DA) uptake inhibitor 1-thienyl)cyclohexyl>piperidine (BTCP, 3) were each prepared in four steps from the appropriate cycloalkanones.These compounds were tested for their ability to displace BTCP and cocaine and to inhibit DA uptake in rat striatal homogenates.The ratios IC50(cocaine)/IC50(BTCP) ranged from 62 for BTCP to 1.5 for 1-(2-benzothienyl)cyclopentylamine (17); cocaine gave a ratio of 0.6.This indicates that BTCP is the most selective of all the compounds tested for sites labeled by BTCP whereas cocaine is most selective for sites labeled by cocaine.The wide differences in the relative abilities of these compounds to displace BTCP and cocaine suggests that these two radioligands are labeling different sites on the transporter.In general, the compounds structurally related to BTCP exhibited greater selectivity for sites labeled by BTCP.However, several of the BTCP-related derivatives showed greater (compared with BTCP and cocaine) ability to displace cocaine.Most notably, 1-thienyl)cyclohexyl>pyrrolidine (7) exhibited a 3.4-fold greater affinity for these sites compared with BTCP and a 9-fold greater affinity at these sites than cocaine.Most of the BTCP homologues displayed greater ability to inhibit DA uptake in rat forebrain synaptosomes than cocaine.BTCP and 7 were the most potent of all the compounds tested in terms of their ability to inhibit uptake of DA.IC50 ratios for cocaine binding/DA uptake ranged from 0.47 for 1-thienyl)cyclopentyl>homopiperidine (11) to 8.8 for 1-(2-benzothienyl)cyclohexylamine (4).The importance of thisratio remains unclear in terms of identification of potential cocaine antagonists.As for BTCP, all of the compounds tested showed Ki values > 10 000 nM for displacement of TCP from rat brain homogenates.These compounds were able to displace the highly selective ? receptor probe -(+)-pentazocine from guinea pig brain homogenates with Ki values ranging from 125 to 9170 nM.The significance of their ?-binding activity in light of their dopaminergic properties is unclear.The diverse binding properties of these compounds at the DA-uptake site and their spectrum of inhibitory activities for DA uptake identifies them as a useful base for the development of subtype selective probes at this site.These compounds will allow further study of the structure and function of the "cocaine" receptor as well as the development of potential cocaine antagonists.
Synthesis of Isothiocyanato-1-thienyl)cyclohexyl>piperidines, Potential Irreversible Ligands at the Dopamine Re-uptake Site
Costa, Brian de,George, Clifford,Dominguez, Celia
, p. 1671 - 1680 (2007/10/02)
Isomeric isothiocyanate derivatives 2-7 of the potent dopamine re-uptake (DA) inhibitor 1-thienyl)cyclohexyl>piperidine (BTCP 1) have been synthesized as potential irreversible ligands for this site.NaNO2-CF3CO2H provided a mild procedure for mononitration of the benzothienyl ring of 1 as a route to aryl isothiocyanates 5-7.Novel methodology, utilizing 3,3-ethylenedioxypentane-1,5-diol dimethanesulfonate ester is described for the synthesis of piperidone 13, a precursor for 4-isothiocyanatopiperidine 2.NaBH4 or LiAlH4 reduction of 4-(2-benzothienyl)-4-hydroxycyclohexanone 18 and 4-(2-benzothienyl)-4-(piperidino)cyclohexanone oxime 35 gives the corresponding cis-diol 21 and cis-cyclohexane-1,4-diamine 36 as the major isomers which have been investigated as precursors to the cyclohexane ring isothiocyanates 3 and 4.Alternative routes to 3 and 4 are compared and their stereochemical outcome investigated.
STUDY OF THE RACTION OF SEVERAL KETONE ENOLATES WITH 3-IODOBENZOTHIOPHENE UNDER THERMALLY INITIATED SRN1 REACTION CONDITIONS
Prats, Montserrat,Galvez, Carmen,Beltran, Lluis
, p. 1039 - 1046 (2007/10/02)
The reaction of 3-iodobenzothiophene (1) with the potassium enolates of cyclohexanone (2a), acetone (2b), and acetophenone (2c) in DMSO for 1 h at room temperature in the dark, gave the desired α-hetaryl ketones (3a-c) in low yield.The thermally activated SRN1 reaction with the ion enolate (2a) was studied in more detail and it was found that the radical chain SRN1 mechanism could compete with one of ionic character.
