- Development of selective inhibitors for the treatment of rheumatoid arthritis: (R)-3-(3-(Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)pyrrolidin-1-yl)-3-oxopropanenitrile as a JAK1-selective inhibitor
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A series of 3(R)-aminopyrrolidine derivatives were designed and synthesized for JAK1-selective inhibitors through the modification of tofacitinib's core structure, (3R,4R)-3-amino-4-methylpiperidine. From the new core structures, we selected (R)-N-methyl-N-(pyrrolidin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine as a scaffold for further SAR studies. From biochemical enzyme assays and liver microsomal stability tests, (R)-3-(3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)pyrrolidin-1-yl)-3-oxopropanenitrile (6) was chosen for further in vivo test through oral administration. Compound 6 showed improved selectivity for JAK1 compared to that of tofacitinib (IC50 11, 2.4 × 102, 2.8 × 103, and 1.1 × 102 nM for JAK1, JAK2, JAK3, and TYK2, respectively). In CIA and AIA model tests, compound 6 exhibited similar efficacy to tofacitinib citrate.
- Chough, Chieyeon,Joung, Misuk,Lee, Sunmin,Lee, Jaemin,Kim, Jong Hoon,Kim, B. Moon
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p. 1495 - 1510
(2018/02/19)
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- JANUS KINASE 1 SELECTIVE INHIBITOR AND PHARMACEUTICAL USE THEREOF
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Janus kinase 1 selective inhibitors and pharmaceutical use thereof are provided.
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Paragraph 0083-0085
(2018/06/07)
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- HETEROARYL COMPOUNDS AND THEIR USE AS MER INHIBITORS
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Compounds of formula (I) [Formula should be inserted here] and a pharmaceutically acceptable salt thereof, wherein A, R1, R2, R3, R4, R5, R6, R7, R24, X, L, n and p are as defined in the specification, are useful for treating or preventing Mer tyrosine kinase receptor modulated disease or conditions. Also described are pharmaceutical compositions of compounds of formula (I), and methods for using such compounds and compositions.
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Paragraph 1944
(2018/04/27)
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- Novel angular benzophenazines: Dual topoisomerase I and topoisomerase II inhibitors as potential anticancer agents
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A series of substituted angular benzophenazines were prepared using a new synthetic route via a novel regiocontrolled condensation of 1,2-naphthoquinones and 2,3-diaminobenzoic acids. The synthesis and biological activity of this new series of substituted
- Vicker, Nigel,Burgess, Luke,Chuckowree, Irina S.,Dodd, Rory,Folkes, Adrian J.,Hardick, David J.,Hancox, Timothy C.,Miller, Warren,Milton, John,Sohal, Sukhjit,Wang, Shouming,Wren, Stephen P.,Charlton, Peter A.,Dangerfield, Wendy,Liddle, Chris,Mistry, Prakash,Stewart, Alistair J.,Denny, William A.
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p. 721 - 739
(2007/10/03)
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- Synthesis and structure-activity relationships of naphthamides as dopamine D3 receptor ligands
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A series of naphthamides were synthesized, and the affinities of these compounds were determined for dopamine D2 and D3 receptors using radioligand binding techniques. The naphthamide compounds that were prepared include N-(1- alkylp
- Huang,Luedtke,Freeman,Wu,Mach
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p. 1815 - 1826
(2007/10/03)
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- An efficient conversion of chiral α-amino acids to enantiomerically pure 3-amino cyclic amines
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Enantiomerically pure 3-amino cyclic amines such as 3-amino pyrrolidine, 3-amino piperidine, and 2,3,4,5,6,7-hexahydro-1H-azepine have been synthesized in high yields from the optically active natural α-amino acids such as L-aspartic acid, L-glutamic acid, L-2-aminoadipic acid, and their enantiomers.
- Moon, Sung-Hwan,Lee, Sujin
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p. 3919 - 3926
(2007/10/03)
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