- Design, Synthesis, and Bioevaluation of 2-Aminopteridin-7(8H)-one Derivatives as Novel Potent Adenosine A2A Receptor Antagonists for Cancer Immunotherapy
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In recent years, the adenosine A2A receptor (A2AR) has shown exciting progress in the development of immunotherapies for the treatment of cancer. Herein, a 2-amino-7,9-dihydro-8H-purin-8-one compound (1) was identified as an A2AR antagonist hit through in-house library screening. Extensive structure-activity relationship (SAR) studies led to the discovery of 2-aminopteridin-7(8H)-one derivatives, which showed high potencies on A2AR in the cAMP assay. Compound 57 stood out with an IC50 value of 8.3 ± 0.4 nM against A2AR at the 5′-N-ethylcarboxamidoadenosine (NECA) level of 40 nM. The antagonistic effect of 57 was sustained even at a higher NECA concentration of 1 μM, which mimicked the adenosine level in the tumor microenvironment (TME). Importantly, 57 enhanced T cell activation in both the IL-2 production assay and the cancer-cell-killing model, thus demonstrating its potential as a lead for developing novel A2AR antagonists in cancer immunotherapy.
- Yu, Fazhi,Zhu, Chenyu,Ze, Shuyin,Wang, Haojie,Yang, Xinyu,Liu, Mingyao,Xie, Qiong,Lu, Weiqiang,Wang, Yonghui
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supporting information
p. 4367 - 4386
(2022/03/14)
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- Sustainable Route Toward N-Boc Amines: AuCl3/CuI-Catalyzed N-tert-butyloxycarbonylation of Amines at Room Temperature
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N-tert-butoxycarbonyl (N-Boc) amines are useful intermediates in synthetic/medicinal chemistry. Traditionally, they are prepared via an indirect phosgene route with poor atom economy. Herein, a step- and atom-economic synthesis of N-Boc amines from amines, t-butanol, and CO was reported at room temperature. Notably, this N-tert-butyloxycarbonylation procedure utilized ready-made substrates, commercially available AuCl3/CuI as catalysts, and O2 from air as the sole oxidant. This catalytic system provided unique selectivity for N-Boc amines in good yields. More significantly, gram-scale preparation of medicinally important N-Boc amine intermediates was successfully implement, which demonstrated a potential application prospect in industrial syntheses. Furthermore, this approach also showed good compatibility with tertiary and other useful alcohols. Investigations of the mechanisms revealed that gold catalyzed the reaction and copper acted as electron transfer mediator in the catalytic cycle.
- Cao, Yanwei,Huang, Yang,He, Lin
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- [TPA][Pro] ionic liquid as efficient reaction medium for N-tert-Boc protection of amines
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A facile and efficient N-tert-Boc protection of amines is described by the reaction of various primary, secondary, benzylic and aryl amines with di-tert-butyl dicarbonate in the ionic liquid [TPA][Pro] at room temperature. All the N-tert-butylcarbamates are afforded in excellent yields. A catalyst-free method was developed and the ionic liquid [TPA][Pro] can be recovered and reused for several times without loss of its activity.
- Vijaya Durga,Rambabu,Srinivasa Reddy,Hari Babu
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p. 1313 - 1316
(2017/05/02)
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- General Procedures for the Lithiation/Trapping of N-Boc Piperazines
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To provide α-substituted piperazines for early stage medicinal chemistry studies, a simple, general synthetic approach is required. Here, we report the development of two general and simple procedures for the racemic lithiation/trapping of N-Boc piperazin
- Firth, James D.,O'Brien, Peter,Ferris, Leigh
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p. 7023 - 7031
(2017/07/17)
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- Chelating Bis(1,2,3-triazol-5-ylidene) Rhodium Complexes: Versatile Catalysts for Hydrosilylation Reactions
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NHC-rhodium complexes (NHC=N-heterocyclic carbenes) have been widely used as efficient catalysts for hydrosilylation reactions. However, the substrates were mostly limited to reactive carbonyl compounds (aldehydes and ketones) or carbon-carbon multiple bonds. Here, we describe the application of newly-developed chelating bis(tzNHC)-rhodium complexes (tz=1,2,3-triazol-5-ylidene) for several reductive transformations. With these catalysts, the formal reductive methylation of amines using carbon dioxide, the hydrosilylation of amides and carboxylic acids, and the reductive alkylation of amines using carboxylic acids have been achieved under mild reaction conditions.
- Nguyen, Thanh V. Q.,Yoo, Woo-Jin,Kobayashi, Shu
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p. 452 - 458
(2016/02/12)
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- NOVEL CEPHEM COMPOUND HAVING CATECHOL OR PSEUDO-CATECHOL STRUCTURE
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The present invention provides a novel compound which has a wide antimicrobial spectrum, and in particular exhibits potent antimicrobial activity against beta-lactamase producing Gram negative bacteria. Specifically, the present invention provides a compound of the formula (I): wherein each symbol is as defined in the specification, or an amino-protected compound when the amino group is present on the ring in the 7-side chain, or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising the same.
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Paragraph 0392
(2014/03/25)
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- HETEROCYCLIC COMPOUND
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Provided is a compound useful for the prophylaxis or treatment of cancer. The present invention relates to a compound represented by formula (I): wherein each symbol in the formula is as defined in the specification, or a salt thereof or a prodrug thereof, which is useful for the prophylaxis or treatment of cancer.
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Page/Page column 69
(2013/02/28)
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- Nonsolvent application of ionic liquids: Organo-catalysis by 1-alkyl-3-methylimidazolium cation based room-temperature ionic liquids for chemoselective N-tert-butyloxycarbonylation of amines and the influence of the C-2 hydrogen on catalytic efficiency
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1-Alkyl-3-methylimidazolium cation based ionic liquids efficiently catalyze N-tert-butyloxycarbonylation of amines with excellent chemoselectivity. The catalytic role of the ionic liquid is envisaged as "electrophilic activation" of di-tert-butyl dicarbonate (Boc2O) through bifurcated hydrogen bond formation with the C-2 hydrogen of the 1-alkyl-3-methylimidazolium cation and has been supported by a downfield shift of the imidazolium C-2 hydrogen of 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([bmim][NTf2]) from δ 8.39 to 8.66 in the presence of Boc2O in the 1H NMR and a drastic reduction of the catalytic efficiency with 1-butyl-2,3-dimethylimidazolium ionic liquids that are devoid of the C-2 hydrogen. The differential time required for reaction with aromatic and aliphatic amines has offered means for selective N-t-Boc formation during inter and intramolecular competitions. Preferential N-t-Boc formation with secondary aliphatic amine has been achieved in the presence of primary aliphatic amine. Comparison of the catalytic efficiency for N-t-Boc formation with a common substrate revealed that [bmim][NTf2] is superior to the reported Lewis acid catalysts.
- Sarkar, Anirban,Roy, Sudipta Raha,Parikh, Naisargee,Chakraborti, Asit K.
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experimental part
p. 7132 - 7140
(2011/10/08)
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- Amberlyst-15: a mild, efficient and reusable heterogeneous catalyst for N-tert-butoxycarbonylation of amines
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A mild and versatile method has been developed for the chemoselective N-tert-butoxycarbonylation of amines in the presence of Amberlyst-15 under solvent-free condition. The method is general for the preparation of N-Boc derivatives of aliphatic (acyclic and cyclic) and aromatic amines.
- Kumar, K. Shiva,Iqbal, Javed,Pal, Manojit
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experimental part
p. 6244 - 6246
(2010/01/11)
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- AMIDE COMPOUND
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An object of the present invention is to provide a novel fused-ring compound which has a FAAH inhibitory effect and is useful as an analgesic. The present invention relates to a compound represented by formula (I): wherein symbols are as defined in the specification, or salt thereof.
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Page/Page column 20
(2009/07/10)
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- CATALYTIC RADIOFLUORINATION
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One aspect of the present invention relates to a method of preparing radio fluorinated substituted alkyl, cycloalkyl, aryl, and alkenyl compounds. In a preferred embodiment, potassium fluoride-18 is used. Another aspect of the invention relates to arylammonium compounds containing fluorine-18 that are useful as imaging agents. In certain embodiments, the ammonium compound is a tetraaryl ammonium salt. Another aspect of the invention relates to arylsulfonium compounds containing fluorine-18 that are useful as imaging agents. In certain embodiments, the sulfonium compound is a triaryl sulfonium salt. Another aspect of the present invention relates to a method of obtaining a positron emission image of a mammal, comprising the steps of administering to a mammal a compound of the invention, and acquiring a positron emission spectrum of the mammal.
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Page/Page column 96
(2010/11/30)
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- An efficient and chemoselective Br?nsted acidic ionic liquid-catalyzed N-Boc protection of amines
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The first report of a Br?nsted acidic ionic liquid, 1-methylimidazolium tetrafluoroborate [(HMIm)BF4], catalyzed efficient and chemoselective N-Boc protection of various amines using (Boc)2O is presented. Optically pure amino alcohols and amino acid esters were converted efficiently to their corresponding optically pure N-Boc derivatives. The reported method is mild, solvent-free and has the advantages of both homogeneous and heterogeneous catalysis with high product yields, selectivity and ease of product separation.
- Sunitha, Sadula,Kanjilal, Sanjit,Reddy, P. Srinivasa,Prasad, Rachapudi B.N.
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p. 2527 - 2532
(2008/09/19)
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- Asymmetric hydrogenation of quinolines catalyzed by iridium complexes of monodentate BINOL-derived phosphoramidites
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The monodentate BINOL-derived phosphoramidite PipPhos is used as ligand for the iridium-catalyzed asymmetric hydrogenation of 2- and 2,6-substituted quinolines. If tri-ortho-tolylphosphine and/or chloride salts are used as additives enantioselectivities are strongly enhanced up to 89%. NMR indicates that no mixed complexes are formed upon addition of tri-ortho-tolylphosphine.
- Mrsic, Natasa,Lefort, Laurent,Boogers, Jeroen A. F.,Minnaard, Adriaan J.,Feringa, Ben L.,De Vries, Johannes G.
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experimental part
p. 1081 - 1089
(2009/05/27)
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- Molecular iodine-catalyzed facile procedure for N-Boc protection of amines
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An efficient and practical protocol for the protection of various structurally and electronically divergent aryl and aliphatic amines using (Boc)2O in the presence of a catalytic amount of molecular iodine (10 mol%) under solvent-free conditions at ambient temperature is presented.
- Varala, Ravi,Nuvula, Sreelatha,Adapa, Srinivas R.
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p. 8283 - 8286
(2007/10/03)
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- Active esters of N-substituted piperazine acetic acids, including isotopically enriched versions thereof
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In some embodiments, this invention pertains to active esters of N-substituted piperazine acetic acid, including isotopically enriched versions thereof. In some embodiments, this invention pertains to methods for the preparation of active esters of N-subs
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Page/Page column 10-11
(2008/06/13)
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- Isotopically enriched N-substituted piperazines and methods for the preparation thereof
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In some embodiments, this invention pertains to isotopically enriched N-substituted piperazines. In some embodiments, this invention pertains to methods for the preparation of isotopically enriched N-substituted piperazines.
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Page/Page column 10-11
(2008/06/13)
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- Isotopically enriched N-substituted piperazine acetic acids and methods for the preparation thereof
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In some embodiments, this invention pertains to isotopically enriched N-substituted piperazine acetic acids. In some embodiments, this invention pertains to methods for the preparation of isotopically enriched N-substituted piperazine acetic acids.
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Page/Page column 10-11
(2008/06/13)
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- CATALYTIC RADIOFLUORINATION
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One aspect of the present invention relates to a method of preparing radiofluorinated substituted alkyl, cycloalkyl, aryl, and alkenyl compounds. In a preferred embodiment, potassium fluoride-18 is used. Another aspect of the invention relates to piperazine compounds containing fluorine-18 that are useful as imaging agents. In certain embodiments, the piperazine compounds contain a quaternary amine. Another aspect of the invention relates to arylphosphonium compounds containing fluorine-18 that are useful as imaging agents. In certain embodiments, the phosphonium compound is a tetraaryl phosphonium sait. Another aspect of the present invention relates to a method of obtaining a positron emission image of a mammal, comprising the steps of administering to a mammal a compound of the invention, and acquiring a positron emission spectrum of the mammal.
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Page/Page column 74
(2008/06/13)
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- Certain aryl-aliphatic and heteroaryl-aliphatic piperazinyl pyrazines and their use in the treatment of serotonin-related diseases
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Compounds of the general formula (I): wherein the variables are as defined in the specification are useful for the prophylaxis or treatment of serotonin-related, especially 5-HT2receptor-related, diseases in human beings or animals, particularly diseases related to the 5-HT2creceptor, especially diseases such as eating disorders, memory disorders, schizophrenia, mood disorders, anxiety disorders, pain, sexual dysfunctionions, and urinary disorders.
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- Synthesis of Potential Metabolites of 4-Methyl-1-piperazine
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4-Methyl-1-piperazine (1) is an experimental antifilarial drug.In order to investigate its metabolic fate in laboratory animals and also man several potential metabolites, arising from general metabolic conversions of 1, viz.N-oxidation (8), N-demethylation and acetylation (11) and (12), desulphuration (15), nitro group reduction to aryl amino (16) and further acetylation to arylacetamido (17), have been synthesized for identification/quantitation purposes.
- Anjaneyulu B.
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p. 657 - 661
(2007/10/02)
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