- Synthesis, Nicotinic Acetylcholine Receptor Binding, and in Vitro and in Vivo Pharmacological Properties of 2′-Fluoro-(substituted thiophenyl)deschloroepibatidine Analogues
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The synthesis, nAChR in vitro and in vivo pharmacological properties of 2′-fluoro-3′-(substituted thiophenyl)deschloroepibatidine analogues (5a-f, 6a-d, and 7a-c) are presented herein. All had subnanomolar affinity at α4β2*-nAChRs. Contrary to lead structure epibatidine, a potent nAChR agonist, all were potent α4β2- and α3β4-AChR antagonists in an in vitro functional assay. In vivo, the compounds were also nAChR antagonists with various degrees of agonist activity. Compounds 5e, 5f, 6a, 6c, 6d, and 7c had no agonist effects in the tail-flick, hot-plate, hypothermia, or spontaneous activity tests, whereas 5a-d, 7a and 7b did not have agonist activity in the tail-flick and hot-plate tests but, like varenicline, were agonists in the hypothermia and spontaneous activity tests. Compound 6b had agonist activity in all four in vivo tests. All the compounds were antagonists of nicotine-induced antinociception in the tail-flick test, and all except 5c, 5d, 5f, and 6b were antagonists of nicotine-induced antinociception in the hot-plate test. Compound 7c, which had a Ki = 0.86 nM in the binding assay similar potency at α4β2/α3β4 with selectivity relative to α7 nAChRs, had an AD50 value of 0.001 μg/kg in the tail-flick test with no agonist activity in the in vitro or in vivo test had one of the more interesting profiles.
- Ondachi, Pauline W.,Castro, Ana H.,Sherman, Benjamin,Luetje, Charles W.,Damaj, M. Imad,Mascarella, S. Wayne,Navarro, Hernán A.,Carroll
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- -4,4′-dicarboxamide: A novel building block for semiconducting polymers
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A novel electron deficient building block [2,2′-bithiophene]-4,4′-dicarboxamide (BTDCA) was designed to lower the highest occupied molecular orbital (HOMO) energy level of polythiophenes in order to achieve a higher open circuit voltage (Voc) and thus a higher power conversion efficiency in polymer solar cells (PSCs). BTDCA dibromo monomers were conveniently synthesized in four steps, and were used to prepare three thiophene-based D-A polymers, P(BTDCA66-BT) (66BT), P(BTDCA44-BT) (44BT) and P(BTDCA44-TT) (44TT). All the polymers exhibited unipolar hole transport properties, exhibiting mobilities in the range of ~10-4 to 10-2 cm2 V-1 s-1 with the highest hole mobility of up to 1.43 × 10-2 cm2 V-1 s-1 achieved for 44BT in bottom-gate bottom-contact organic thin film transistors (OTFTs). In PSCs, these polymers achieved high Voc's of 0.81-0.87 V when PCBM or ITIC was used as acceptor. When 44TT was used as donor and ITIC was used as acceptor, a power conversion efficiency (PCE) of up to 4.5% was obtained, a significant improvement when compared with the poly(3-hexylthiophene) (P3HT):ITIC devices, which showed the highest PCE of merely 0.92%.
- Zhou, Xiaocheng,Zhang, Zhifang,Hendsbee, Arthur D.,Ngai, Jenner H. L.,Kumar, Pankaj,Ye, Shuyang,Seferos, Dwight S.,Li, Yuning
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- Thermal behaviour of dicarboxylic ester bithiophene polymers exhibiting a high open-circuit voltage
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Nine different polythiophene derivatives based on dialkyl-(2,2′-bithiophene-5,5′-diyl)-4,4′-dicarboxylate (DCB) alternating with thiophene (T), bithiophene (2T) or thienothiophene (TT) as co-monomer have been synthesized to study the effect of the polymer backbone and side chain length on the thermal properties, the tendency to aggregate, and the photovoltaic performance. Polymers incorporating DCB and 2T show increased crystallinity and a large effect of the side chain length on the morphology of the photoactive layer blends. Thermal annealing increases the crystallinity of the polymers and enhances the long-wavelength light absorption. The concomitant increase in polymer fibre width, however, deteriorates the photovoltaic performance. The best devices were made using the PDCB-2T polymer with 2-butyloctyl side chains providing a power conversion efficiency of 5.18%. The PDCB-T polymer with 2-ethylhexyl substituents shows a comparable efficiency (5.08%), but with a significantly higher open-circuit voltage due to deeper frontier orbitals levels.
- Heuvel, Ruurd,Colberts, Fallon J.M.,Wienk, Martijn M.,Janssen, René A.J.
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- METHODS AND COMPOUNDS FOR RESTORING MUTANT p53 FUNCTION
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Mutations in oncogenes and tumor suppressors contribute to the development and progression of cancer. The present disclosure describes compounds and methods to recover wild-type function to p53 mutants. The compounds of the present disclosure can bind to mutant p53 and restore the ability of the p53 mutant to bind DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used to reduce the progression of cancers that contain a p53 mutation.
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Paragraph 0935
(2021/11/20)
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- Substituted thiophene compound Preparation method and application thereof (by machine translation)
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The invention relates to a thiophene compound represented by general formula I, a pharmaceutically acceptable salt thereof, a preparation method thereof, a pharmaceutical composition containing the thiophene compound and application thereof. The thiophene compound and a pharmaceutically acceptable salt thereof are taken as a novel estrogen-related receptor α (ERR RR) inverse agonist. These compounds can be used to treat diseases associated with ERR and ERR RR, such as cancer, osteoporosis, diabetes, anti-aging, slimming, and the like. After further optimization and screening, the drug is expected to be developed into novel drugs for preventing and treating tumors or other ERR RR related diseases. (by machine translation)
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Paragraph 0120-0122
(2021/01/11)
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- A Planar-Chiral Rhodium(III) Catalyst with a Sterically Demanding Cyclopentadienyl Ligand and Its Application in the Enantioselective Synthesis of Dihydroisoquinolones
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The rapid development of enantioselective C?H activation reactions has created a demand for new types of catalysts. Herein, we report the synthesis of a novel planar-chiral rhodium catalyst [(C5H2tBu2CH2tBu)RhI2]2 in two steps from commercially available [(cod)RhCl]2 and tert-butylacetylene. Pure enantiomers of the catalyst were obtained through separation of its diastereomeric adducts with natural (S)-proline. The catalyst promoted enantioselective reactions of aryl hydroxamic acids with strained alkenes to give dihydroisoquinolones in high yields (up to 97 %) and with good stereoselectivity (up to 95 % ee).
- Trifonova, Evgeniya A.,Ankudinov, Nikita M.,Mikhaylov, Andrey A.,Chusov, Denis A.,Nelyubina, Yulia V.,Perekalin, Dmitry S.
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supporting information
p. 7714 - 7718
(2018/04/25)
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- Amide-bridged terphenyl and dithienylbenzene units for semiconducting polymers
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We here describe the synthesis, characterization, and structures of new semiconducting polymers (PIQP2T and PTPQ2T) based on amide-bridged terphenyl (IQP) and dithienylbenzene (TPQ), and their performances in organic field-effect transistors (OFETs) and organic photovoltaics (OPVs). The polymers are found to have relatively wide band gaps of >2.0 eV and deep HOMO energy levels of -5.4 eV. Interestingly both the HOMO and LUMO energy levels similarly shift upward and downward, respectively, by the π-extension from the monomer unit to the polymer, which can be ascribed to the delocalized HOMO and LUMO along the molecular frameworks. This suggests that IQP and TPQ can be viewed as electron-neutral building units. Both polymers had similar ordering structures in the thin film despite the fact that the IQP is more sterically hindered at the end of the moiety than TPQ. This is probably due to the strong intermolecular interactions originating in the amide group. The polymers exhibited similar hole mobilities of 0.03-0.04 cm2 V-1 s-1 in the OFET devices. Although the PCEs were modest, the OPV devices based on these polymers showed a quite high VOC of 0.94 V.
- Akita, Masahiro,Saito, Masahiko,Osaka, Itaru,Koganezawa, Tomoyuki,Takimiya, Kazuo
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p. 16437 - 16447
(2016/02/20)
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- 1,2,4-TRIAZINE-6-CARBOXAMIDE DERIVATIVE
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The present invention provides a compound represented by the following general formula (I) or a salt thereof which has a Syk inhibitory effect (in the formula R1 represents a hydrogen atom or an optionally Ra-substituted C1-C6 alkyl group; A represents a hydrogen atom, an optionally Ra-substituted C1-C8 alkyl group, an optionally Ra-substituted C2-C6 alkenyl group, an optionally Ra-substituted C2-C6 alkynyl group, an optionally Rb-substituted C3-C10 cycloalkyl group, an optionally Rb-substituted C6-C14 aromatic hydrocarbon group, an optionally Rb-substituted 4- to 10-membered unsaturated heterocyclic group, or an optionally Rb-substituted 4-to 10-membered saturated heterocyclic group, or optionally forms a 4- to 10-membered unsaturated heterocyclic ring or a 4- to 10-membered saturated heterocyclic ring together with R1 and the nitrogen atom bonded thereto; R2 represents a hydrogen atom or an optionally Ra-substituted C1-C6 alkyl group; and B represents an optionally Rc-substituted unsaturated heterocyclic group).
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Paragraph 0351
(2014/08/19)
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- Macrocycles with bithiophene units: Synthesis, structure, and electrochemical properties
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Bithiophene macrocycles with oligo(oxyethylene) loops were synthesized in good yields by reacting 4,40-bis(hydroxymethyl)-2,20-bithiophene with ditosylated oligoethyleneglycols. The structures of the macrocycles were elucidated by NMR spectroscopy and MS spectrometry. The electronic and electrochemical properties of the macrocyclic compounds were determined using cyclic voltammetry and UV-Vis spectroscopy. Copyright
- Dora Demeter,Claudia Lar,Jean Roncali,Grosu, Ion
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p. 1460 - 1462
(2013/05/08)
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- Selective photoinduced energy transfer from a thiophene rotaxane to acceptor
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An energy transfer process was investigated using cyclodextrin- oligothiophene rotaxanes (2T-[2]rotaxane). The excited energy of 2T-[2]rotaxane is transferred to the sexithiophene derivative which is included in the cavity of β-CD stoppers of 2T-[2]rotaxane.
- Sakamoto, Kazuya,Takashima, Yoshinori,Hamada, Norio,Ichida, Hideki,Yamaguchi, Hiroyasu,Yamamoto, Hitoshi,Harada, Akira
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supporting information; experimental part
p. 672 - 675
(2011/04/17)
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- (4-PHENYL-PIPERIDIN-1-YL)-[5-1H-PYRAZOL-4YL)-THIOPHEN-3-YL]-METHANONE COMPOUNDS AND THEIR USE
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The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain (4-phenyl-piperidin-1-yl)- [5-(1 H-pyrazol-4-yl)-thiophen-3-yl]-methanone compounds that, inter alia, inhibit 11 β-hydroxysteroid dehydrogenase type 1 (11 β-HSD1 ). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit 1 1 β-hydroxysteroid dehydrogenase type 1; to treat disorders that are ameliorated by the inhibition of 11 β-hydroxysteroid dehydrogenase type 1; to treat the metabolic syndrome, which includes disorders such as type 2 diabetes and obesity, and associated disorders including insulin resistance, hypertension, lipid disorders and cardiovascular disorders such as ischaemic (coronary) heart disease; to treat CNS disorders such as mild cognitive impairment and early dementia, including Alzheimer's disease; etc.
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Page/Page column 71-72
(2011/04/19)
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- Influence of the annealing temperature on the photovoltaic performance and film morphology applying novel thermocleavable materials
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Di-2-thienyl-2,1,3-benzothiadiazole (DTBT) bearing thermally cleavable ester groups in different positions were prepared and copolymerized with alkylsubstituted cyclopentadithiophene (CPDT). The polymers were found to have band gaps in the range of 1.66-2.03 eV and were explored in polymer photovoltaic devices as mixtures with soluble methanofullerenes. The positioning of the ester groups proved to be very significant despite the identical conjugated backbone of 2-methyl-2-hexyl 5-(4,4-bis(2-ethylhexyl)-4H-cyclopenta[1,2-b:5,4- b′]dithiophen-2-yl)-2-(7-(3-(((2-methylhexan-2-yl)oxy)-carbonyl) thiophen-2-yl)benzo[c][1,2,5]thiadiazol-4-yl)thiophene-3-carboxylate (T1) and 2-methyl-2-hexyl 2-(4,4-bis(2-ethylhexyl)-4H-cyclopenta[1,2-b:5,4-b′] dithiophen-2-yl)-5-(7-(4-(((2-methylhexan-2-yl)oxy)carbonyl)thiophen-2-yl) benzo[c][1,2,5]thiadiazol-4-yl)thiophene-3-carboxylate (T2). Power conversion efficiencies of up to 1.92% were observed for polymers bearing ester groups on the 4-positions of the thienyl groups (T2), but shifting them to the 3-positions (T1) reduced the efficiency significantly to 0.18%. The thermal behavior of the polymers was studied with thermogravimetric analysis (TGA) that showed a weight loss around 200 °C corresponding to elimination of the ester side chains followed by a second weight loss around 300 °C corresponding to loss of CO2 via decarboxylation. The temperature of thermocleavage of the active layer films was optimized to 265 °C whereby the T2:PCBM solar cells maintained a significant performance giving efficiencies up to 1.49%.
- Helgesen, Martin,Bjerring, Morten,Nielsen, Niels Chr.,Krebs, Frederik C.
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scheme or table
p. 5617 - 5624
(2011/12/15)
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- FUSED HETEROCYCLYC INHIBITOR COMPOUNDS
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The present invention provides a compound of general Formula (I) having histone deacetylase (HDAC) and/or Cyclin-dependent kinase (CDK) inhibitory activity, a pharmaceutical composition comprising the compound, and a method useful to treat diseases using the compound
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Page/Page column 110
(2010/03/02)
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- THIENOPYRIDAZINE COMPOUNDS, THEIR PREPARATIONS, PHARMACEUTICAL COMPOSITIONS AND USES
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The present invention relates to thienopyridazine compounds of formula (I), their pharmaceutically acceptable salts or hydrates, wherein R1 and R2 are independently H or C1-4 alkyl, R3 is a saturated or unsaturated 5- or 6- membered ring containing N, S or O, or its optical isomers, R4 is a halophenyl monosubstituted or disubstituted at any position. The present invention provides the preparation methods of these compounds, pharmaceutical compositions containing these compounds and the uses of these compounds, particularly in treating cancer.
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Page/Page column 25
(2010/11/03)
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- ORGANIC COMPOUNDS
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The present invention provides heterocyclic derivatives that modulate the activity of stearoyl-CoA desaturase. Methods of using such derivatives to modulate the activity of stearoyl-CoA desaturase and pharmaceutical compositions comprising such derivatives are also encompassed.
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(2009/07/03)
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- DIAZACARBAZOLES AND METHODS OF USE
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The invention relates to 1,7-diazacarbazole compounds of Formula (I), (I-a) and (I-b) which are useful as kinase inhibitors, more specifically useful as checkpoint kinase 1 (chkl) inhibitors, thus useful as cancer therapeutics. The invention also relates to compositions, more specifically pharmaceutical compositions comprising these compounds and methods of using the same to treat various forms of cancer and hyperproliferative disorders, as well as methods of using the compounds for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.
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(2010/01/07)
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- Novel Compounds and Therapeutic Use Thereof for Protein Kinase Inhibition
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Novel compound having the following formula: Also disclosed are a pharmaceutical compositions comprising the same, methods for treating cancer using the same, and methods for the synthesis of the same. The novel compounds of the present invention are found to inhibit protein kinases, especially Checkpoint kinase Chk1/Chk2.
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Page/Page column 12; 16
(2009/12/02)
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- INHIBITORS OF AKT ACTIVITY
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Invented are novel heterocyclic carboxamide compounds, the use of such compounds as inhibitors of protein kinase B activity and in the treatment of cancer and arthritis.
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(2008/12/08)
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- AZAINDOLES USEFUL AS INHIBITORS OF ROCK AND OTHER PROTEIN KINASES
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The present invention relates to compounds useful as inhibitors of protein kinases. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.
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(2008/06/13)
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- THIENOPYRIDAZINES AS IKK INHIBITORS
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The invention is concerned with a compound of formula (I): or a pharmaceutically acceptable salt, a solvate or a prodrug thereof, wherein A, Y, Z and Rl are as defined in the description and the claims. These compounds inhibit IKK and can be used as medicaments.
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(2008/06/13)
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- INDANE DERIVATES AS MUSCARINIC RECEPTOR AGONISTS
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The present invention relates to compounds of Formula I: I which are agonists of the M-1 muscarinic receptor.
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- Heterocyclic compound having oxime group
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The present invention provides a compound that has an excellent inhibitory activity on STAT6 activation and is effective against allergic diseases, and a medicinal composition thereof. According to the present invention, disclosed is the compound represented by the General Formula (I) [where R1 and R2 independently represent a C1-6 alkyl group and the like that may have a hydrogen atom or a substituent; R3 represents a C1-6 alkyl group and the like that may have a substituent; R4 and R5 independent represents a hydrogen atom or a C1-6 alkyl group and the like that may have a substituent; R6 represents a hydrogen atom and the like; W represents —SO2— and the like; and X represents a sulphur atom and the like.]or a salt thereof, or a hydrate thereof.
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(2010/02/14)
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- NOVEL COMPOUNDS THAT MODULATE PPARγ TYPE RECEPTORS, AND USE THEREOF IN COSMETIC OR PHARMACEUTICAL COMPOSITIONS
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The invention relates to novel compounds corresponding to the general formula (I) below: (I) and also to the method for preparing them, and to their use in pharmaceutical compositions intended for use in human or veterinary medicine (in dermatology, and also in the fields of cardiovascular diseases, immune diseases and/or diseases associated with lipid metabolism),-or alternatively in cosmetic compositions.
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- THIOPHENE-CARBOXAMIDE DERIVATIVES AND THEIR USE AS INHIBITORS OF THE ENZIME IKK-2
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The invention relates to thiophene carboxamides of formula (I), wherein A, R1, R2, R3, R4, R5 and X are as defined in the specification, processes and intermediates used in their preparation, pharmaceutical compositions containing them and their use in therapy.
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- THIOPHENE CARBOXAMIDES AS INHIBITORS OF THE ENZYME IKK-2
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The invention relates to thiophene carboxamides of formula (I) wherein Ar, R1, R2, R3, R4, R5, m and n are as defined in the specification, processes and intermediates used in their preparation, pharmaceutical compositions containing them and their use in therapy.
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- Compounds
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Compounds of formula I: wherein A, D, Ar1, E and Ar2 are as defined in the specification, processes for preparing them, pharmaceutical compositions containing them and their use in therapy, especially in the treatment or prophylaxis of psychotic and intellectual impairment disorders.
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- Poly(alkyl thiophene-3-carboxylates). Synthesis, properties and electroluminescence studies of polythiophenes containing a carbonyl group directly attached to the ring
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Improved synthetic methodology for poly(3-hexyl- and 3- octyloxycarbonylthiophene-2,5-diyl) (1a and 1b) is reported. M(n) = 6700 and 9400 (M(w)/M(n) = 2.5 and 3.2), λ(max) for fluorescence emission = 600 and 610 nm and λ(max) for electroluminescence = 600 and 615 nm, for 1a and 1b respectively. The 1H NMR spectra required that pentads be considered to explain the spectra. That is the four nearest neighbours to a given ring influence the 1H NMR spectrum. Electroluminescence efficiencies of 0.016% and 0.018% were observed for devices made from 1a and 1b, respectively. A bilayer device of ITO/poly(3-octylthiophene)/1b/A1 emitted at 646 nm, the same wavelength where poly(3-octylthiophene) itself emits. The efficiency was low but was an order of magnitude greater than for poly(3-octylthiophene) itself. Regioregular (HH-TT) poly(4,4'-bis(hexyl- and octyloxycarbonyl)[2,2'- bithiophene]-5,5'-diyl) (3a and 3b) were also prepared via the Ullmann reaction and M(n) = 7900 and 11000 respectively. Films of 3a and 3b were yellow in color and showed λ(max) = 377 and 381 nm respectively, about 55-80 nm blue shifted compared with 1a and 1b. This is due to the large rotational barrier in the HH dyads which reduces the effective conjugation length in 3a and 3b. 3a and 3b showed bright fluorescence and electroluminescence with emission of yellow light. Electroluminescence efficiencies were 8.5 x 10-3% and 4.7 x 10-3%, respectively.
- Pomerantz, Martin,Cheng, Yang,Kasim, Ramesh K.,Elsenbaumer, Ronald L.
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p. 2155 - 2163
(2007/10/03)
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- Phosphorylamides, their preparation and use
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A phosphorylamide derivative represented by the general formula (I): STR1 wherein R represents an amino group that may be substituted, or a salt thereof, possesses potent antibacterial activity against Helicobacter bacterium, especially Helicobacter pylori, and is useful for prevention or treatment of digestive diseases caused by Helicobacter bacterium, solely or in combination with an antacid or an acid secretion inhibitor.
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- Fungicides for the control of take-all disease of plants
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A method of controlling Take-All disease of plants by applying a fungicide of the formula STR1 wherein Z1 and Z2 are C and are part of an aromatic ring which is benzothiophene; and A is selected from --C(X)-amine wherein the amine is an unsubstituted, monosubstituted or disubstituted amino radical, --C(O)--SR3, --NH--C(X)R4, and --C(=NR3)--XR7 ; B is --Wm --Q(R2)3 or selected from O-tolyl, 1-naphthyl, 2-naphthyl, and 9-phenanthryl, each optionally substituted with halogen or R4 ; Q is C, Si, Ge, or Sn; W is --C(R3)p H(2-p) --; or when Q is C, W is selected from --C(R3)p H(2-p), --N(R3)m H(1-m)--, --S(O)p--, and --O--; X is 0 or S; n is 0, 1, 2, or 3; m is 0 or 1; p is 0, 1, or 2; each R and R2 is independently defined herein; R3 is C1 -C4 alkyl; R4 is C1 -C4 alkyl, haloalkyl, alkoxy, alkylthio, alkylamino, or dialkylamino; and R7 is C1 -C4 alkyl, haloalkyl, or phenyl, optionally substituted with halo, nitro, or R4 ; or an agronomic salt thereof.
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- Herbicidal Thienylureas, I
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Syntheses of the title substances as potential herbicides are described by a modified Curtius degradation of corresponding thiophene carboxylic acids, obtained in turn by haloform reaction of appropriate acetyl thiophenes.Regioselective substitution reactions of thiophenes were key steps for the construction of desired substitution patterns.Structure-activity considerations show that especially the 3-thienyl ureas 36 and 38 exhibit significant herbicidal activity comparable with commercial products. - Keywords: Curtius degradation; Herbicides; Thiophenes; Ureas; Urethanes
- Stanetty, Peter,Puschautz, Erhard,Friedbacher, Gernot
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- Pharmaceutical compositions containing thiophene compounds, and new thiophene compounds
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A pharmaceutical composition containing a thiophene compound of formula: STR1 where R1, R2, R3 and R4 have the meanings given in the description, or a pharmaceutically acceptable addition salt thereof. Said pharmaceutical compositions are useful in treating tumors. New thiophene compounds are also described.
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