- Preparation method of chiral 1-tert-butyl-3-methyl-6-methylpiperazine-1, 3-diformate
-
The invention provides a preparation method of chiral 1-tert-butyl-3-methyl-6-methylpiperazine-1, 3-diformate, and particularly relates to a preparation method of (3R,6R) -1-tert-butyl-3-methyl-6-methylpiperazine-1, 3-diformate. The preparation method comprises the steps of taking Boc-D-alanine and L-serine methyl ester hydrochloride as initial raw materials, and preparing the chiral 1-tert-butyl-3-methyl-6-methylpiperazine-1, 3-diformate through condensation reaction, deamination protection, ring closing reaction, reduction reaction, amino protection, oxidation reaction, ring closing reactionand ring opening reaction. According to the preparation method provided by the invention, the Boc amino protective agent is used for protecting amino, so that the production cost is reduced, the rawmaterials are easy to obtain, the conditions are mild, the yield is relatively high, and the preparation method can be applied to large-scale industrial production.
- -
-
Paragraph 0135; 0140-0142; 0157; 0161-0162; 0173; 0177-0178
(2021/02/06)
-
- SUBSTITUTED NAPHTHYRIDINONE COMPOUNDS USEFUL AS T CELL ACTIVATORS
-
Disclosed are compounds of Formula (I) or a salt thereof, wherein: R1, R2, R3, R4, R5, and m are defined herein. Also disclosed are methods of using such compounds to inhibit the activity of one or both of diacylglycerol kinase alpha (DGKα) and diacylglycerol kinase zeta (DGKζ), and pharmaceutical compositions comprising such compounds. These compounds are useful in the treatment of viral infections and proliferative disorders, such as cancer.
- -
-
Page/Page column 736; 737
(2020/01/24)
-
- Structure-based design and pharmacokinetic optimization of covalent allosteric inhibitors of the mutant gtpase krasg12c
-
Attempts to directly drug the important oncogene KRAS have met with limited success despite numerous efforts across industry and academia. The KRASG12C mutant represents an "Achilles heel" and has recently yielded to covalent targeting with small molecules that bind the mutant cysteine and create an allosteric pocket on GDP-bound RAS, locking it in an inactive state. A weak inhibitor at this site was optimized through conformational locking of a piperazine-quinazoline motif and linker modification. Subsequent introduction of a key methyl group to the piperazine resulted in enhancements in potency, permeability, clearance, and reactivity, leading to identification of a potent KRASG12C inhibitor with high selectivity and excellent cross-species pharmacokinetic parameters and in vivo efficacy.
- Kettle, Jason G.,Bagal, Sharan K.,Bickerton, Sue,Bodnarchuk, Michael S.,Breed, Jason,Carbajo, Rodrigo J.,Cassar, Doyle J.,Chakraborty, Atanu,Cosulich, Sabina,Cumming, Iain,Davies, Michael,Eatherton, Andrew,Evans, Laura,Feron, Lyman,Fillery, Shaun,Gleave, Emma S.,Goldberg, Frederick W.,Harlfinger, Stephanie,Hanson, Lyndsey,Howard, Martin,Howells, Rachel,Jackson, Anne,Kemmitt, Paul,Kingston, Jennifer K.,Lamont, Scott,Lewis, Hilary J.,Li, Songlei,Liu, Libin,Ogg, Derek,Phillips, Christopher,Polanski, Radek,Robb, Graeme,Robinson, David,Ross, Sarah,Smith, James M.,Tonge, Michael,Whiteley, Rebecca,Yang, Junsheng,Zhang, Longfei,Zhao, Xiliang
-
p. 4468 - 4483
(2020/06/08)
-
- TETRACYCLIC HETEROARYL COMPOUNDS
-
The specification relates to compounds of Formula (I) and pharmaceutically acceptable salts thereof. The specification also relates to processes and intermediates used for their preparation, pharmaceutical compositions containing them and their use in the treatment of cell proliferative disorders.
- -
-
Page/Page column 135
(2020/01/10)
-
- CHEMICAL COMPOUNDS
-
The specification relates to compounds of Formula (I) and pharmaceutically acceptable salts thereof. The specification also relates to processes and intermediates used for their preparation, pharmaceutical compositions containing them and their use in the treatment of cell proliferative disorders.
- -
-
Paragraph 0348; 0527-0528
(2019/06/20)
-
- Fragment-Based Drug Discovery Targeting Inhibitor of Apoptosis Proteins: Discovery of a Non-Alanine Lead Series with Dual Activity Against cIAP1 and XIAP
-
(Figure Presented) Inhibitor of apoptosis proteins (IAPs) are important regulators of apoptosis and pro-survival signaling pathways whose deregulation is often associated with tumor genesis and tumor growth. IAPs have been proposed as targets for anticanc
- Chessari, Gianni,Buck, Ildiko M.,Day, James E. H.,Day, Philip J.,Iqbal, Aman,Johnson, Christopher N.,Lewis, Edward J.,Martins, Vanessa,Miller, Darcey,Reader, Michael,Rees, David C.,Rich, Sharna J.,Tamanini, Emiliano,Vitorino, Marc,Ward, George A.,Williams, Pamela A.,Williams, Glyn,Wilsher, Nicola E.,Woolford, Alison J.-A.
-
supporting information
p. 6574 - 6588
(2015/09/07)
-
- BICYCLIC HETEROCYCLE COMPOUNDS AND THEIR USES IN THERAPY
-
The invention relates to new bicyclic heterocycle compounds, to pharmaceutical compositions comprising said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.
- -
-
Page/Page column 107
(2015/07/07)
-
- BICYCLIC HETEROCYCLE COMPOUNDS AND THEIR USES IN THERAPY
-
The invention relates to new bicyclic heterocycle compounds of formula (I): wherein R1 is seected from specific pyrazolyl, imidazolyl, pridinyl and triazolyl groups. The invention also realtes to pharmaceutical compositions comprising said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.
- -
-
Page/Page column 91; 92
(2014/05/07)
-
- BICYCLIC HETEROCYCLE COMPOUNDS AND THEIR USES IN THERAPY
-
The invention relates to new bicyclic heterocycle compounds of formula (I): (Formula (I)), pharmaceutical compositions comprising said compounds and to use of said compounds in the treatment of diseases, e.g. cancer.
- -
-
Page/Page column 99. 100
(2014/05/07)
-
- BICYCLIC HETEROCYCLE COMPOUNDS AND THEIR USES IN THERAPY
-
The invention relates to new bicyclic heterocycle compounds of formula (I):,to pharmaceutical compositions comprising said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.
- -
-
Page/Page column 122; 123
(2014/05/07)
-
- BICYCLIC HETEROCYCLE COMPOUNDS AND THEIR USES IN THERAPY
-
The invention relates to bicyclic heterocycle compounds of formula (I): or tautomeric or stereochemically isomeric forms, N-oxides, pharmaceutically acceptable salts or the solvates thereof; wherein R1, R2a, R2b, R3a, R3b, R5, R6, R7, R8, R9, p and E are as defined herein; to pharmaceutical compositions comprising said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.
- -
-
Page/Page column 119
(2012/11/07)
-