- AN ACTIVITY-GUIDE MAP OF ELECTROPHILE-CYSTEINE INTERACTIONS IN PRIMARY HUMAN IMMUNE CELLS
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Disclosed herein are methods, pharmaceutical compositions, and vaccines for modulating an immune response. Also disclosed herein are methods, pharmaceutical compositions, and vaccines for inducing an immune response.
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Paragraph 0250-0251; 0262-0263
(2021/04/23)
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- Organocatalytic Cascade Reactions for the Diversification of Thiopyrano-Piperidone Fused Rings Utilizing Trienamine Activation
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An aminocatalytic privileged diversity-oriented synthesis (ApDOS) strategy utilizing trienamine catalysis for the construction of diverse and complex thiopyrans-piperidone fused rings through a thia-Diels–Alder/nucleophilic ring-closing sequence by using dithioamides as activated heterodienophiles is reported. Following this strategy, a super cascade reaction to assemble nine fused rings can be achieved by employing a bis-dithioamide. Additionally, by linking an indole moiety on the dithioamide, a Pictet–Spengler type reaction can be promoted once the cascade sequence has been achieved, leading to more complex penta- hexa- and heptacyclic fused ring derivatives in a one-pot process. This investigation opens new perspectives for the synthesis of a new class of complex and diverse thiopyrans that contribute to populate new relevant regions in the chemical space.
- Mitkari, Suhas Balasaheb,Medina-Ortíz, Alberto,Olivares-Romero, José Luis,Vázquez, Miguel A.,Pe?a-Cabrera, Eduardo,Villegas Gómez, Clarisa,Cruz Cruz, David
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supporting information
p. 618 - 621
(2020/12/11)
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- Insecticidal activity of indole derivatives against Plutella xylostella and selectivity to four non-target organisms
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The diamondback moth Plutella xylostella (Linnaeus, 1758) (Lepidoptera: Plutellidae) is a destructive pest of brassica crops of economic importance that have resistance to a range of insecticides. Indole derivates can exert diverse biological activities, and different effects may be obtained from small differences in their molecular structures. Indole is the parent substance of a large number of synthetic and natural compounds, such as plant and animal hormones. In the present study, we evaluate the insecticidal activity of 20 new synthesized indole derivatives against P. xylostella, and the selectivity of these derivatives against non-target hymenopteran beneficial arthropods: the pollinator Apis mellifera (Linnaeus, 1758) (Hymenoptera: Apidae), and the predators Polybia scutellaris (White, 1841), Polybia sericea (Olivier, 1791) and Polybia rejecta (Fabricius, 1798) (Hymenoptera: Vespidae). Bioassays were performed in the laboratory to determine the lethal and sublethal effects of the compounds on P. xylostella and to examine their selectivity to non-target organisms by topical application and foliar contact. The treatments consisted of two synthesized derivatives (most and least toxic), the positive control (deltamethrin) and the negative control (solvent). The synthesized compound 4e [1-(1H-indol-3-yl)hexan-1-one] showed high toxicity (via topical application and ingestion) and decreased the leaf consumption by P. xylostella, displaying a higher efficiency than the pyrethroid deltamethrin, widely used to control this pest. In addition, the synthesized indole derivatives were selective to the pollinator A. mellifera and the predators P. scutellaris, P. sericea and P. rejecta, none of which were affected by deltamethrin. Our results highlight the promising potential of the synthesized indole derivatives for the generation of new chemical compounds for P. xylostella management.
- Costa, ?ngela C. F.,Cavalcanti, Sócrates C. H.,Santana, Alisson S.,Lima, Ana P. S.,Brito, Thaysnara B.,Oliveira, Rafael R. B.,Macêdo, Nathália A.,Cristaldo, Paulo F.,Araújo, Ana Paula A.,Bacci, Leandro
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p. 973 - 982
(2019/08/26)
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- COMPOSITIONS AND METHODS OF MODULATING IMMUNE RESPONSE
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Disclosed herein are methods, pharmaceutical compositions, and vaccines for modulating an immune response. Also disclosed, herein are methods, pharmaceutical compositions, and vaccines for inducing an immune response.
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Paragraph 0318; 0329; 0330
(2018/01/17)
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- 8-aminoquinoline-melatonin complex and pharmaceutical composition thereof
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The invention relates to synthesized 8-aminoquinoline-melatonin complex, in particular to an 8-aminoquinoline-melatonin complex and a pharmaceutical composition thereof. The 8-aminoquinoline-melatonin complex is of a structure as shown in the structural formula (I); on one hand, the compounds can selectively chelate copper ions; on the other hand, the compounds play a role in well protecting nerves and nerve cells to improve AD (Alzheimer's disease) symptoms. The invention further relates to a pharmaceutical composition or nerve cell protective agent comprising the complex or pharmaceutically acceptable salt thereof. The invention further relates to pharmaceutical application of the complex.
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Paragraph 0058; 0061
(2017/02/17)
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- Synthesis, biological evaluation, and structure-activity relationships of potent noncovalent and nonpeptidic cruzain inhibitors as anti-Trypanosoma cruzi agents
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The development of cruzain inhibitors has been driven by the urgent need to develop novel and more effective drugs for the treatment of Chagas' disease. Herein, we report the lead optimization of a class of noncovalent cruzain inhibitors, starting from an inhibitor previously cocrystallized with the enzyme (Ki = 0.8 μM). With the goal of achieving a better understanding of the structure-activity relationships, we have synthesized and evaluated a series of over 40 analogues, leading to the development of a very promising competitive inhibitor (8r, IC50 = 200 nM, Ki = 82 nM). Investigation of the in vitro trypanocidal activity and preliminary cytotoxicity revealed the potential of the most potent cruzain inhibitors in guiding further medicinal chemistry efforts to develop drug candidates for Chagas' disease.
- Ferreira, Rafaela S.,Dessoy, Marco A.,Pauli, Ivani,Souza, Mariana L.,Krogh, Renata,Sales, Ana I. L.,Oliva, Glaucius,Dias, Luiz C.,Andricopulo, Adriano D.
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supporting information
p. 2380 - 2392
(2014/04/17)
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- Synthesis, activity, and QSAR studies of tryptamine derivatives on third-instar larvae of aedes aegypti linn
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Special attention has been given to the mosquito Aedes aegypti Linn. (Diptera: Culicidae) owing to numerous dengue epidemic outbreaks worldwide. Failure to control vector spreading is accounted for unorganized urban growth and resistance to larvicides and insecticides. Therefore, researchers are currently searching for new and more efficient larvicides and insecticides to aid dengue control measures. Triptamine is known to affect insect behavior, development, and physiology. Expression of this compound in plants has reduced the growth rate of herbivore insects. In view of these facts, it was of our interest to synthesize triptamine amide derivatives as potential larvicides against Ae. aegypti, establishing a Structure-Activity Relationship. Eleven amide derivatives of triptamine were synthesized, characterized, and evaluated for their larvicidal activity against third-instar Ae. aegypti larvae. N-(2-(1H-indol-3-yl)ethyl)-2,2,2-trichloroacetamide exhibited the highest overall larvicidal potency, while N-(2-(1H-Indol-3-yl)ethyl) acetamide displayed the lowest larvicidal potency. A regression equation correlating the larvicidal activity with Log P was obtained. We have found a clear relationship between the larvicidal activity of non-chlorinated compounds and Log P. Analysis of the relationship between Log P and larvicidal activity against Ae. aegypti may be useful in the evaluation of potential larvicidal compounds.
- Oliveira, Rafael R.B.,Brito, Thaysnara B.,Nepel, Angelita,Costa, Emmanoel V.,Barison, Andersson,Nunes, Rogéria S.,Santos, Roseli L.C.,Cavalcanti, Sócrates C.H.
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p. 580 - 587
(2014/11/07)
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- Bioreduction of β-carboline imines to amines employing Saccharomyces bayanus
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β-Carboline imine reductions mediated by Saccharomyces bayanus have been described achieving moderate to good enantiomeric excesses of the amine products. The enantiomeric excesses of the bioreduction showed a dependence on the imine substituents. Compoun
- Espinoza-Moraga, Marlene,Petta, Tania,Vasquez-Vasquez, Marco,Laurie, V. Felipe,Moraes, Luis A.B.,Santos, Leonardo Silva
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body text
p. 1988 - 1992
(2010/11/05)
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- Synthesis of bioactive 2-aza-analogues of ipecac and alangium alkaloids
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License to kill: Substitution of the methine carbon C2 in the ipecac or alangium alkaloids by nitrogen yields functional mimetics with low micromolar to high naonomolar IC50 values against Trypanosoma brucei, the parasite that causes African tr
- Koelzer, Michael,Weitzel, Kerstin,Goeringer, H. Ulrich,Thines, Eckhard,Opatz, Till
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scheme or table
p. 1456 - 1464
(2011/11/29)
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- Novel synthesis of pyridazino[4,5-b][1,4]oxazin-3,8-diones
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A novel and effective synthesis of pyridazino[4,5-b][1,4]oxazin-3,8-diones via Smiles rearrangement is presented. Treatment of N-substituted 2-chloro(or hydroxy)acetamide, 2-tetrahydropyranyl-4-chloro-5-hydroxy(or chloro)pyridazin-3-one and cesium carbonate in refluxing acetonitrile was afforded the corresponding pyridazino[4,5-b][1,4]oxazin-3,8-diones in excellent yield.
- Cho, Su-Dong,Song, Sang-Yong,Park, Yong-Dae,Kim, Jeum-Jong,Joo, Woo-Hong,Shiro, Motoo,Falck,Shin, Dong-Soo,Yoon, Yong-Jin
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p. 8995 - 8998
(2007/10/03)
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- Regioselective reduction of N-alkyl-3-sulfonylglutarimide. Formal synthesis of 1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizine and homobaclofen
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Reduction of N-alkyl-3-sulfonylglutarimides with (1) sodium hydride and then with lithium aluminum hydride, or (2) sodium borohydride yielded two different types of regioselectively reduced hydroxypiperidinones which were further dehydrated to two pyridin-2-ones in the presence of boron trifluoride etherate. Cycloaddition and regioselective reduction were combined to synthesize 1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizine and homobaclofen.
- Chang, Meng-Yang,Chen, Shui-Tein,Chang, Nein-Chen
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- Synthesis of fused bicyclic glutarimides
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We describe an efficient route towards the synthesis of fused bicyclic glutarimides using facile [3+3] reaction of α-sulfonylacetamides with different α,β-unsaturated esters as the key step. Intramolecular cyclization of 4-substituted 3-sulfonylglutarimide to form 5,6-, 6,6- or 6,7-fused bicyclic glutarimides was accomplished via alkylation, oxidative cyclization or ring-closing metathesis in modest yield.
- Chang, Meng-Yang,Chen, Chung-Yi,Chen, Shui-Tein,Chang, Nein-Chen
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p. 7547 - 7553
(2007/10/03)
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- Reaction of different α-sulfonyl acetamides with methyl acrylate
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The base-induced tandem-coupling/cyclization reactions of various α-sulfonyl acetamide derivatives A with methyl acrylate differentiated between two different pathways to form α-sulfonyl analogs of glutarimides B and 2-hydroxycyclohexenecarboxylic acid derivatives C in different ratios. The reaction of α-sulfonyl acetamide dianion with methyl acrylate depended on three factors: the stability of the dianion, concentration of methyl acrylate and the structure of sufonyl and amide substituents. By changing the reaction conditions, we efficiently controlled the cycloaddition reaction to synthesize the desired product, each of which has potential biological activities. A ring closure mechanism is proposed for the reactions.
- Chang, Meng-Yang,Chen, Shui-Tein,Chang, Nein-Chen
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p. 5075 - 5080
(2007/10/03)
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- An efficient synthesis of N-alkyl-4-substituted 3H-pyridine-2,6-dione. Synthesis of isoguvacine and MDL-11,939
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An efficient route towards the synthesis of N-alkyl-4-substituted 3H-pyridine-2,6-dione using various N-alkyl-α-sulfonylacetamides and two α,β-unsaturated esters as starting materials is described. Isoguvacine and MDL-11,939 with have potential biological activities were synthesized via this strategy.
- Chang, Meng-Yang,Chen, Shui-Tein,Chang, Nein-Chen
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p. 2321 - 2334
(2007/10/03)
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- (1S)-1-(Aminomethyl)-2-(arylacetyl)-1,2,3,4-tetrahydroisoquinoline and heterocycle-condensed tetrahydropyridine derivatives: Members of a novel class of very potent κ opioid analgesics
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The synthesis and structure-activity relationship (SAR) of a novel class of κ opioid analgesics, 1-(amino-methyl)-2-(arylacetyl)-1,2,3,4-tetrahydroisoquinolines and (aminomethyl)-N-(arylacetyl)-4,5,6,7-tetrahydrothienopyridines, are described. These compounds, formally derived by the condensation of a benzene or thiophene ring on the piperidine nucleus of the recently described compounds 1, are from 3 to 7 times more potent as antinociceptive agents and with a longer duration of action than the original lead compounds. A similar N2-C1-C9-N10 pharmacophore torsional angle of approximately 60° was also found for this class of compounds by using X-ray and 1H NMR analyses. The same absolute configuration (S) at the chiral center of the active (-) enantiomers was determined by X-ray crystallographic analysis. A varied degree of κ receptor selectivity was a feature of this novel class of antinociceptive agents (μ/κ ratio from 44 to 950 according to the nature of the basic moiety). A SAR analysis indicated that the presence of electron-withdrawing and lipophilic substituents in para and/or meta positions in the arylacetic moiety and the pyrrolidino or dimethylamino basic groups are required to optimize biological activity. The lead compounds 28, 30, and 48 are among the most potent antinociceptive agents (ED50 ca. 0.020 μM/kg sc) and κ ligands (K(i)(κ) ca. 0.20 nM) identified so far.
- Vecchietti,Clarke,Colle,Giardina,Petrone,Sbacchi
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p. 2624 - 2633
(2007/10/02)
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