- Minimization of Back-Electron Transfer Enables the Elusive sp3 C?H Functionalization of Secondary Anilines
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Anilines are some of the most used class of substrates for application in photoinduced electron transfer. N,N-Dialkyl-derivatives enable radical generation α to the N-atom by oxidation followed by deprotonation. This approach is however elusive to monosubstituted anilines owing to fast back-electron transfer (BET). Here we demonstrate that BET can be minimised by using photoredox catalysis in the presence of an exogenous alkylamine. This approach synergistically aids aniline SET oxidation and then accelerates the following deprotonation. In this way, the generation of α-anilinoalkyl radicals is now possible and these species can be used in a general sense to achieve divergent sp3 C?H functionalization.
- Zhao, Huaibo,Leonori, Daniele
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supporting information
p. 7669 - 7674
(2021/03/08)
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- PDIA4 INHIBITORS AND USE THEREOF FOR INHIBITING ?-CELL PATHOGENESIS AND TREATING DIABETES
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Disulfide-Isomerase A4 (PDIA4) inhibitors and use thereof for inhibiting pancreatic β-cell pathogenesis and treating diabetes are disclosed. Drug candidates that inhibit PDIA4 with IC50 values ranging from 4 μM to 300 nM are identified. The compounds are highly active in augmenting insulin secretion from pancreatic β-cells. The representative compound No. 8 (4,5-dimethoxy-2-propiolamidobenzoic acid), alone or in combination with metformin, is effective in preserving pancreatic β-cell function, treating and/or reversing, returning blood glucose concentration to a normal level in a diabetic.
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Page/Page column 7
(2021/06/11)
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- OXOACRIDINYL ACETIC ACID DERIVATIVES AND METHODS OF USE
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Compounds of Formulae I, II, their pharmaceutically acceptable salts or esters thereof capable of binding to and modulating the activity of a stimulator of interferon genes (STING) protein are provided. Methods involving compounds of Formulae I or II as effective modulators of STING are also provided.
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- TRICYCLIC COMPOUNDS AS HISTONE METHYL-TRANSFERASE INHIBITORS
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The present disclosure provides certain tricyclic compounds that are histone methyltransferases G9a and/or GLP inhibitors and are therefore useful for the treatment of diseases treatable by inhibition of G9a and/or GLP such as cancers and hemoglobinopathi
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Page/Page column 162
(2019/03/05)
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- PHARMACEUTICAL COMPOSITION AND APPLICATION REPLACING QUINOLONE DERIVATIVE, PHARMACEUTICAL ACCEPTABLE SALT, OR STEREOISOMER
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Provided are a substituted quinolone derivative as shown by formula (I), or a pharmaceutically acceptable salt and a prodrug molecule thereof, and a pharmaceutical composition thereof, as well as the use of same in preparing drugs for the prevention and treatment of a tumor. The quinolone derivative, salt, prodrug molecule, and pharmaceutical composition thereof can be used as a protein kinase inhibitor, which is effective in inhibiting the activity of AXL protein kinase, and is capable of inhibiting the proliferation, migration and invasion of various tumor cells; and can be used in the preparation of anti-tumor drugs, especially drugs for treating hyperproliferative diseases such as a tumor in human beings and other mammals.
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Paragraph 0163; 0164
(2018/07/06)
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- Dioxolone structure containing 4 - N substituted quinazoline derivatives and its preparation and use (by machine translation)
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The invention discloses a dioxolone structure containing 4 -NSubstituted quinazoline derivatives, its structure such as shown in I. This invention has introduced to substituted benzoic acid, methanol, nitric acid, formamide, trichloro oxygen phosphorus chlorine, nitrobenzene formaldehyde, acetone, stannous chloride, substituted aromatic aldehyde as raw material, by the multi-step reaction to synthesize the target compound. The compounds can be used as anti-tumor, anti-bacterial plant and anti-plant-virus of the drug. (1 E, 4 E) - 1 - substituted phenyl - 5 - (4 - (substituted quinazoline - 4 - amino) phenyl) - 1, 4 - pentadiene - 3 - one. (by machine translation)
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- The first radiosynthesis of [11C]AZD8931 as a new potential PET agent for imaging of EGFR, HER2 and HER3 signaling
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The reference standard AZD8931{2-(4-((4-((3-chloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)piperidin-1-yl)-N-methylacetamide} (11a) was synthesized from methyl 4,5-dimethoxy-2-nitrobenzoate or ethyl 4,5-dimethoxy-2-nitrobenzoate and 2-chloro-N-methylacetamide in 11 steps with 2-5% overall chemical yield. The precursor N-desmethyl-AZD8931{2-(4-((4-((3-chloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)piperidin-1-yl)acetamide} (11b) was synthesized from methyl 4,5-dimethoxy-2-nitrobenzoate or ethyl 4,5-dimethoxy-2-nitrobenzoate and 2-bromoacetamide in 11 steps with 2-4% overall chemical yield. The target tracer [11C]AZD8931 {2-(4-((4-((3-chloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)piperidin-1-yl)-N-[11C]methylacetamide} ([11C]11a) was prepared from N-desmethyl-AZD8931 (11b) with [11C]CH3OTf under basic condition (NaH) through N-[11C]methylation and isolated by HPLC combined with solid-phase extraction (SPE) in 40-50% radiochemical yield based on [11C]CO2and decay corrected to end of bombardment (EOB) with 370-1110 GBq/μmol specific activity at EOB.
- Wang, Min,Gao, Mingzhang,Zheng, Qi-Huang
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p. 4455 - 4459
(2014/12/11)
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- Broensted acid-catalyzed one-pot synthesis of indoles from o-aminobenzyl alcohols and furans
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Broensted acid-catalyzed one-pot synthesis of indoles from o-aminobenzyl alcohols and furans has been developed. This method operates via the in situ formation of aminobenzylfuran, followed by its recyclization into the indole core. The method proved to be efficient for substrates possessing different functional groups, including -OMe, -CO2Cy, and -Br. The resulting indoles can easily be transformed into diverse scaffolds, including 2,3- and 1,2-fused indoles, and indoles possessing an α,β-unsaturated ketone moiety at the C-2 position.
- Kuznetsov, Alexey,Makarov, Anton,Rubtsov, Aleksandr E.,Butin, Alexander V.,Gevorgyan, Vladimir
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p. 12144 - 12153
(2014/01/06)
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- Discovery of novel bacterial RNA polymerase inhibitors: Pharmacophore-based virtual screening and hit optimization
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The bacterial RNA polymerase (RNAP) is a validated target for broad spectrum antibiotics. However, the efficiency of drugs is reduced by resistance. To discover novel RNAP inhibitors, a pharmacophore based on the alignment of described inhibitors was used for virtual screening. In an optimization process of hit compounds, novel derivatives with improved in vitro potency were discovered. Investigations concerning the molecular mechanism of RNAP inhibition reveal that they prevent the protein-protein interaction (PPI) between σ70 and the RNAP core enzyme. Besides of reducing RNA formation, the inhibitors were shown to interfere with bacterial lipid biosynthesis. The compounds were active against Gram-positive pathogens and revealed significantly lower resistance frequencies compared to clinically used rifampicin.
- Hinsberger, Stefan,Hüsecken, Kristina,Groh, Matthias,Negri, Matthias,Haupenthal, J?rg,Hartmann, Rolf W.
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p. 8332 - 8338
(2013/12/04)
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- STEROIDAL ANTI-HORMONE HYBRIDS
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Disclosed are novel compounds and compositions for inhibition of androgen and estrogen receptor signaling, methods for inhibiting androgen signaling, methods for inhibiting estrogen signaling, methods for inhibiting the interaction between a co-regulatory protein and an androgen or estrogen receptor, and methods for treating cancer.
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Page/Page column 45
(2010/08/08)
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- An efficient selective reduction of aromatic azides to amines employing BF3·OEt2/NaI: Synthesis of pyrrolobenzodiazepines
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A selective and facile method for the reduction of aromatic azides to amines by employing borontrifluoride diethyl etherate and sodium iodide. This methodology has been applied towards the preparation of biologically important imine-containing pyrrolobenzodiazepines and their dilactams through intramolecular reductive-cyclization process. In this protocol the reagent systems are amenable for the generation of solution-phase combinatorial synthesis. Georg Thieme Verlag Stuttgart.
- Kamal, Ahmed,Shankaraiah,Markandeya,Reddy, Ch. Sanjeeva
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experimental part
p. 1297 - 1300
(2009/04/06)
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- Synthesis and Pharmacological Evaluation of Fenamate Analogues: 1,3,4-Oxadiazol-2-ones and 1,3,4-Oxadiazole-2-thiones
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A series of fenamate pyridyl or quinolinyl analogues of 1,3,4-oxadiazol-2-ones 5a-d and 6a-r, and 1,3,4-oxadiazole-2-thiones 5e-g and 6s-v, respectively, have been synthesized and evaluated for their analgesic (hot-plate), antiinflammatory (carrageenin induced rat's paw edema) and ulcerogenic effects as well as plasma prostaglandin E2 (PGE 2) level. The highest analgesic activity was achieved with compound 5a (0.5, 0.6, 0.7 mmol/kg b.wt.) in respect with mefenamic acid (0.4 mmol/kg b.wt.). Compounds 6h, 61 and 5g showed 93, 88 and 84% inhibition, respectively on the carrageenan-induced rat's paw edema at dose level of 0.1mmol/kg, b.wt, compared with 58% inhibition of mefenamic acid (0.2mmol/kg b.wt.). Moreover, the highest inhibitory activity on plasma PGE2 level was displayed also with 6h, 61 and 5g (71, 70, 68.5% respectively, 0.1mmol/kg b.wt.) compared with indomethacin (60%, 0.01 mmol/kg b.wt.) as a reference drug. In addition 6i, 6k, 6p, 6r, 6t and 6v were devoid of any ulcerogenicity.
- El-Azzounyl, Aida A.,Maklad, Yousreya A.,Bartsch, Herbert,Zaghary, Wafaa A.,Ibrahim, Waleed M.,Mohamed, Mosaad S.
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p. 331 - 356
(2007/10/03)
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- Simple and facile reduction of azides to amines: Synthesis of DNA interactive pyrrolo[2,1-c][1,4]benzodiazepines
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The reduction of aromatic azido compounds to the corresponding amines with hydriodic acid has been investigated and found to result in high yields. This reductive methodology which proceeds under non refluxing condition has been extended for the synthesis of DNA-interactive pyrrolo[2,1-c][1,4] benzodiazepine antibiotics.
- Kamal, Ahmed,Reddy,Reddy, D.Rajasekhar
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p. 6629 - 6631
(2007/10/03)
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- Synthesis of 3,4-dihydroxy-6-(N-ethylamino)benzamide, a new phenolic compound isolated from green pepper (Piper nigrum L.) berries
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The synthesis of 3,4-dihydroxy-6-(N-ethylamino)benzamide (9), a novel phenolic constittuent of green pepper berries, responsible for its blackening during drying process has been developed from vanillic acid (1) in eight steps.Use of mild reaction conditions such as employing anhydrous ammonium formate as hydrogen transfer agent during reduction of 3 at room temperature (Step III), reductive alkylation of 4 with sodium borohydride and acetic acid (Step IV) and protecting the amino group using acetic acid (Step IV) and protecting the amino group using trifluoroacetic acid prior to demethylation (Step VII) and hydrolysis (Step VIII) results in an acceptable yield of the final product (9) despite its highly unstable nature.
- Variyar, Prasad S.,Bandyopadhyay, Chiranjib
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p. 911 - 913
(2007/10/03)
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- 4H-3,1-BENZOXAZIN-4-ONES AND RELATED COMPOUNDS AND USE AS ENZYME INHIBITORS
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Novel 2-amino-4H-3,1-benzoxazin-4-ones represented by the formula wherein R 1, R 2, R 3 and X are defined herein are useful as enzyme inhibitors in animals.
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- The Synthesis of the Dimethoxyisatins
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Preparations of all 6 dimethoxyisatins are described.The methods of synthesis of these compounds from anilines have been compared, the route via the 3-(methylthio)oxindoles giving, in general, the best yield.These isatins are strikingly different in colou
- Taylor, A.
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p. 4154 - 4171
(2007/10/02)
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- 3-Alkoxy-thianapthene-2-carboxamides
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The 3-alkoxy-thianaphthene-2-carboxamides of this invention are effective for the treatment of mammals afflicted with emesis. When administered to dogs in dosages of 250 μg/kg, compounds of this invention give 100% protection against vomiting normally induced by subcutaneous administration of apomorphine. The compounds of this invention also favorably modify behavior disturbances in mammals.
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