Electron impact-induced methyl migration in dimethylaminoheteroaromatic systems

Rahamin, Y.; Sharvit, Joseph; Mandelbaum, A.; Sprecher, Milon

doi:10.1021/jo01287a030

Cited by 30 publications

(4 citation statements)

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“…However, in some cases such as many purine nucleosides,19 or dihydrouridine,7•19 the molecular ion may be absent, and so chemical ionization may offer a distinct advantage. One Journal of the American Chemical Society / 97:12 / June II, 1975 (164) 20 (192) 2.0 (164) 14 (192) 2.5 (164) 96 (192) 35 (164) 45 (192) 3.5 (164) 7.5 (192)d ( 204) 76 (232) 3.5 (204) 2.3 (332)d ( 136) 41 (164) 28 (141) 19 (113)d (141) 2.5…”

mentioning

confidence: 99%

Chemical ionization mass spectrometry of nucleosides. Mechanisms of ion formation and estimations of proton affinity

Wilson¹,

McCloskey²

1975

J. Am. Chem. Soc.

169

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mentioning

confidence: 99%

Chemical ionization mass spectrometry of nucleosides. Mechanisms of ion formation and estimations of proton affinity

Wilson¹,

McCloskey²

1975

J. Am. Chem. Soc.

169

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“…Prepared according to general procedure F using 2-chloro-5-nitropyrimidine (300 mg, 1.90 mmol, 1 equiv), Me 2 NH (1.40 mL, 2.80 mmol, 1.5 equiv, 2.0 M in THF), and Et 3 N (288 μL, 2.10 mmol, 1.1 equiv) in THF (8 mL) to give a yellow solid (275 mg, 87%); R f 0.75 (NH 2 SiO 2 , 30% EtOAc/petrol); mp 209–212 °C (lit. 28 222 °C); λ max (EtOH)/nm 341, 219; IR ν max /cm –1 1547, 1301; 1 H NMR (500 MHz; DMSO- d 6 ) δ H 3.31 (6H, s, NMe 2 ), 9.15 (2H, s, 2 × H-pyrimidine); 13 C NMR (125 MHz; DMSO- d 6 ) δ C 37.4 (NMe 2 ), 133.4 (C-5-pyrimidine), 154.8 (2H, s, 2 × CH-pyrimidine), 161.6 (C-2-pyrimidine); HRMS calcd for C 6 H 9 N 4 O 2 [M + H] + 169.0720, found 169.0720.…”

Section: Methodsmentioning

confidence: 99%

Parallel Optimization of Potency and Pharmacokinetics Leading to the Discovery of a Pyrrole Carboxamide ERK5 Kinase Domain Inhibitor

et al. 2022

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The nonclassical extracellular signal-related kinase 5 (ERK5) mitogen-activated protein kinase pathway has been implicated in increased cellular proliferation, migration, survival, and angiogenesis; hence, ERK5 inhibition may be an attractive approach for cancer treatment. However, the development of selective ERK5 inhibitors has been challenging. Previously, we described the development of a pyrrole carboxamide high-throughput screening hit into a selective, submicromolar inhibitor of ERK5 kinase activity. Improvement in the ERK5 potency was necessary for the identification of a tool ERK5 inhibitor for target validation studies. Herein, we describe the optimization of this series to identify nanomolar pyrrole carboxamide inhibitors of ERK5 incorporating a basic center, which suffered from poor oral bioavailability. Parallel optimization of potency and in vitro pharmacokinetic parameters led to the identification of a nonbasic pyrazole analogue with an optimal balance of ERK5 inhibition and oral exposure.

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“…A mechanism is suggested for the loss of C02 from the parent V-methylphthalimide (820), and the methyl migration in dimethylamino heteroaromatic systems is discussed (1246). A mechanism of thermal isomerization of labeled trimethyltriazines is studied by mass spectrometry (1184), and the formation of ions from C02 after electron and ion impact is discussed (1379).…”

Section: Chemical Ionizationmentioning

confidence: 99%