1598-61-4Relevant articles and documents
N-Substituted pyrrolopyrimidines and purines as p90 ribosomal S6 protein kinase-2 (RSK2) inhibitors
Casalvieri, Kimberly A.,Matheson, Christopher J.,Warfield, Becka M.,Backos, Donald S.,Reigan, Philip
supporting information, (2021/06/02)
The RSK2 kinase is the downstream effector of the Ras/Raf/MEK/ERK pathway, that is often aberrantly activated in acute myeloid leukemia (AML). Recently, we reported a structure-activity study for BI-D1870, the pan-RSK inhibitor, and identified pteridinones that inhibited cellular RSK2 activity that did not result in concomitant cytotoxicity. In the current study, we developed a series of pyrrolopyrimidines and purines to replace the pteridinone ring of BI-D1870, with a range of N-substituents that extend to the substrate binding site to probe complementary interactions, while retaining the 2,6-difluorophenol-4-amino group to maintain interactions with the hinge domain and the DFG motif. Several compounds inhibited cellular RSK2 activity, and we identified compounds that uncoupled cellular RSK2 inhibition from potent cytotoxicity in the MOLM-13 AML cell line. These N-substituted probes have revealed an opportunity to further examine substituents that extend from the ATP- to the substrate-binding site may confer improved RSK potency and selectivity.
Cyclin-Dependent Kinase (CDK) Inhibitors: Structure-Activity Relationships and Insights into the CDK-2 Selectivity of 6-Substituted 2-Arylaminopurines
Coxon, Christopher R.,Anscombe, Elizabeth,Harnor, Suzannah J.,Martin, Mathew P.,Carbain, Benoit,Golding, Bernard T.,Hardcastle, Ian R.,Harlow, Lisa K.,Korolchuk, Svitlana,Matheson, Christopher J.,Newell, David R.,Noble, Martin E. M.,Sivaprakasam, Mangaleswaran,Tudhope, Susan J.,Turner, David M.,Wang, Lan Z.,Wedge, Stephen R.,Wong, Christopher,Griffin, Roger J.,Endicott, Jane A.,Cano, Céline
, p. 1746 - 1767 (2017/03/17)
Purines and related heterocycles substituted at C-2 with 4′-sulfamoylanilino and at C-6 with a variety of groups have been synthesized with the aim of achieving selectivity of binding to CDK2 over CDK1. 6-Substituents that favor competitive inhibition at
N-heterocyclic derivatives as NOS inhibitors
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, (2008/06/13)
N-Heterocyclic derivatives of the formula (I): are described herein, as well as other N-heterocycles, as inhibitors of nitric oxide synthase. Pharmaceutical compositions containing these compounds, methods of using these compounds as inhibitors of nitric oxide synthase and processes for synthesizing these compounds are also described herein.
DEAMINATION, INVOLVING RING OPENING, IN REACTIONS OF 1-AMINOPURINIUM MESITYLENESULFONATES WITH METHANOLIC AMMONIA
Kos, N. J.,Jongejan, H.,van der Plas, H. C.
, p. 4841 - 4848 (2007/10/02)
On reaction of 1-aminopurinium mesitylenesulfonates with methanolic ammonia N-deamination occurs.For 1-amino-, 1-amino-8-(methylthio)-, 1-amino-8-phenyl-, 1-amino-2-methyl-, 1-amino-6-methyl- and 1-amino-8-phenyl-9-methylpurinium mesitylenesulfonate this reaction proceeds for at least 75percent via ring opening as shown by the isolation of 1-15N-labelled purines when 15N-labelled methanolic ammonia was used. 1-Amino-9-methylpurinium mesitylenesulfonate gave N-deamination without ring opening.The reaction of 1-amino-6-(methylthio)purinium mesitylenesulfonate with methanolic ammonia involves, besides deamination, partial substitution of the methylthio group; no ring opening is involved.However, ring opening followed by substitution occurs in the reaction of 1-amino-2-(methylthio)purinium mesitylenesulfonate; the reaction proceeds via an adduct at position 2.
