- IRAK DEGRADERS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same.
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Paragraph 00962; 001001-001003; 003421-003422
(2020/06/19)
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- IRAK DEGRADERS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same. The compounds include an IRAK binding moiety and a degradation inducing moiety (DIM). The DIM could be DTM a ligase binding moiety (LBM) or lysine mimetic. The compounds could be useful as IRAK protein kinase inhibitors and applied to IRAK mediated disorders.
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Paragraph 00794; 00836-00838
(2021/01/23)
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- IRAK DEGRADERS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same.
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Paragraph 2321; 2322
(2019/07/10)
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- Synthetic studies towards the core structure of nakadomarin a by a thioamide-based strategy
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The tricyclic BCD substructure of the marine natural product nakadomarin A has been synthesised. The strategy utilised a key carbon-carbon bond-forming reaction between a furan and an N-acyliminium ion derived from a secondary thiolactam. In addition, a novel three-component coupling reaction between a thioamide, an allylic bromide and an isocyanate, leading to the establishment of two new stereogenic centres, is reported. Two key steps in a projected total synthesis of nakadomarin A have been realised by using the unique chemistry of thioamides. Formation of the carbocyclic B ring can be effected by nucleophilic attack of a furan on a thiolactam-derived iminium ion, and the key quaternary centre can be established by a novel three-component coupling reaction.
- Chavda, Jai K.,Procopiou, Panayiotis A.,Horton, Peter N.,Coles, Simon J.,Porter, Michael J.
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p. 129 - 139
(2014/01/06)
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- SUBSTITUTED PYRIDINYL-PYRIMIDINES AND THEIR USE AS MEDICAMENTS
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The invention relates to new substituted pyridinyl-pyrimidines of formula 1 wherein ring A is a five-membered saturated or unsaturated carbocyclic ring which optionally comprises one, two or three heteroatoms each independently from each other selected from the group N, S and O, wherein R1, R2, R4, R3, R5 and R6 are defined as in claim 1 and wherein ring A is further optionally substituted by one or two further substituents and the pharmaceutically acceptable salts, diastereomers, enantiomers, racemates, hydrates and solvates of the aforementioned compounds.
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Paragraph 0322-0324
(2013/03/26)
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- Synthesis, evaluation of anti-HIV-1 and anti-HCV activity of novel 2′,3′-dideoxy-2′,2′-difluoro-4′-azanucleosides
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A series of 2′,3′-dideoxy-2′,2′-difluoro-4′- azanucleosides of both pyrimidine and purine nucleobases were synthesized in an efficient manner starting from commercially available L-pyroglutamic acid via glycosylation of difluorinated pyrrolidine derivative 15. Several 4′-azanucleosides were prepared as a separable mixture of α- and β-anomers. The 6-chloropurine analogue was obtained as a mixture of N 7 and N9 regioisomers and their structures were identified based on NOESY and HMBC spectral data. Among the 4′-azanucleosides tested as HIV-1 inhibitors in primary human lymphocytes, four compounds showed modest activity and the 5-fluorouracil analogue (18d) was found to be the most active compound (EC50 = 36.9 μM) in this series. None of the compounds synthesized in this study demonstrated anti-HCV activity.
- Martínez-Montero, Saúl,Fernández, Susana,Sanghvi, Yogesh S.,Theodorakis, Emmanuel A.,Detorio, Mervi A.,McBrayer, Tamara R.,Whitaker, Tony,Schinazi, Raymond F.,Gotor, Vicente,Ferrero, Miguel
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p. 6885 - 6893
(2013/01/15)
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- SUBSTITUTED PYRIDINYL-PYRIMIDINES AND THEIR USE AS MEDICAMENTS
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The invention relates to new substituted pyridinyl-pyrimidines of formula 1 wherein ring A is a five-membered saturated or unsaturated carbocyclic ring which optionally comprises one, two or three heteroatoms each independently from each other selected from the group N, S and O, wherein R1, R2, R4, R3, R5 and R6 are defined as in claim 1 and wherein ring A is further optionally substituted by one or two further substituents and the pharmaceutically acceptable salts, diastereomers, enantiomers, racemates, hydrates and solvates of the aforementioned compounds.
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Page/Page column 108; 109
(2012/08/08)
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- Synthesis and utility of the 3,3-dimethyl-5-substituted-2-pyrrolidinone 'Quat' chiral auxiliary
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The synthesis and utility of the 3,3-dimethyl-5-substituted-2-pyrrolidinone 'Quat' chiral auxiliary in stereoselective enolate reactions of attached N-acyl side chains combined with the mild and non-racemising conditions required for the ultimate removal of the chiral side chain is described.
- Davies, Stephen G.,Dixon, Darren J.,Doisneau, Gilles J.-M.,Prodger, Jeremy C.,Sanganee, Hitesh J.
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p. 647 - 658
(2007/10/03)
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- Electrophilic fluorination of pyroglutamic acid derivatives: Application of substrate-dependent reactivity and diastereoselectivity to the synthesis of optically active 4-fluoroglutamic acids
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Electrophilic fluorination of enantiomerically pure 2-pyrrolidinones (4) derived from (L)-glutamic acid has been investigated as a method for the synthesis of single stereoisomers of 4-fluorinated glutamic acids. Reaction of the lactam enolate derived from 9 with NFSi results in a completely diastereoselective monofluorination reaction to yield the monocyclic trans-substituted α-fluoro lactam product 21. Unfortunately, a decreased kinetic acidity in 21 and other structurally related monofluorinated products renders them resistant to a second fluorination. In contrast, the bicyclic lactam 12 is readily difluorinated under the standard conditions described to yield the α,α-difluoro lactam 24. The difference in reactivity between the two types of related lactams is attributed mainly to the presence or lack of a steric interaction between the base used for deprotonation and the protecting group present in the pyrrolidinone substrates. This conclusion was reached based on analysis of the X-ray crystal structure of 21, molecular modeling, and experimental evidence. The key intermediates 21 and 24 are converted to (2S,4R)-4-fluoroglutamic acid and (2S)-4,4-difluoroglutamic acid, respectively.
- Konas,Coward
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p. 8831 - 8842
(2007/10/03)
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- Synthesis of L-4,4-difluoroglutamic acid via electrophilic difluorination of a lactam.
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[formula: see text] An enantiomerically pure bicyclic lactam proved to be an excellent substrate for electrophilic difluorination using N-fluorobenzenesulfonimide. The resulting difluorinated lactam can be easily converted into L-4,4-difluoroglutamic acid. To the best of our knowledge, this is the first example of a synthetically useful electrophilic difluorination of an unactivated lactam.
- Konas,Coward
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p. 2105 - 2107
(2008/02/09)
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- Photocycloaddition of α,β-unsaturated-γ-lactam with ethylene. Synthesis of conformationally restricted glutamate analogs, L-2-(2-carboxycyclobutyl)glycines
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Both (2S,1'S,2'S)- and (2S, 1'S,2'R)-isomers of 2-(2-carboxycyclobutyl)glycine (CBG-I, 1b) and (CBG-III, 2b) are synthesized in a stereoselective manner via a [2+2] photocycloaddition of α,β-unsaturated-γ-lactam 3 with ethylene in acetone. The extended type of isomer 1b showed a weak activity on group II metabotropic glutamate receptors (mGluR2) of rat brain.
- Tsujishima, Hidekazu,Nakatani, Kuniko,Shimamoto, Keiko,Shigeri, Yasushi,Yumoto, Noboru,Ohfune, Yasufumi
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p. 1193 - 1196
(2007/10/03)
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- Synthesis of 5-substituted-3,3-dimethyl-2-pyrrolidinones: "Quat" chiral auxiliaries
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The synthesis of a series of chiral auxiliaries, 5-substituted-3,3-dimethyl-2-pyrrolidinones, "quats", from L-glutamic acid is described. Efficient regeneration of the chiral auxiliaries from their N-pivaloyl derivatives is readily achieved with LiOH in THF-water at 20°C.
- Davies, Stephen G.,Doisneau, Gilles J. -M.,Prodger, Jeremy C.,Sanganee, Hitesh J.
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p. 2369 - 2372
(2007/10/02)
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- MOLECULAR MODELING OF γ-LACTAM ANALOGUES OF β-LACTAM ANTIBACTERIAL AGENTS: SYNTHESIS AND BIOLOGICAL EVALUATION OF SELECTED PENEM AND CARBAPENEM ANALOGUES
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Computational chemistry made possible the prediction of the three-dimensional structures of γ-lactam analogues of penems and carbapenems before the analogues were made.Molecular superpositioning showed that these novel structures with a 7β-acylamino side-chain present the pharmacophoric groups in close spatial similarity to the groups in biologically active cephalosporin and penicillin antibiotics.This suggest that 8-oxo-7-acylamino-1-azabicyclooct-2-ene-2-carboxylates and 4-thia-analogues can be accommodated in the same active sites of essential bacterical penicillin-binding proteins where cephalosporins and penicillins are recognized.The syntheses of these compounds are reported.The γ-lactams exhibit low, but detectable levels of antibacterial activity and suggest promise that substantial activity can be achieved with other γ-lactams.
- Allen, Norris E.,Boyd, Donald B.,Campbell, Jack B.,Deeter, Jack B.,Elzey, Thomas K.,et al.
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p. 1905 - 1928
(2007/10/02)
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