Über quaternäre Pyridin‐Basen

Magidson, O. J.; Menschikoff, G.

doi:10.1002/cber.19260590622

Cited by 9 publications

(3 citation statements)

References 4 publications

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“…These alkylation results are consistent with those reported for reactions on 2-aminopyridine by Dome, where mixtures of mono- and dibenzylated products were obtained in moderate yield (35% and 23%, respectively), and by Whitmore, who prepared the 2-(morpholinylpropyl)amino derivative (18%) by heating the preformed anion with 0.5 equiv of the alkyl chloride in toluene. However, selective monoalkylation of 2-aminopyridine in better yield has been reported , via the corresponding 2-formamide or acetamide (whereas 2-sulfonamides reportedly gave alkylation on the ring nitrogen).…”

Section: Chemistrymentioning

confidence: 99%

“…The extracts were evaporated to dryness and the residue was then chromatographed on silica gel. Elution with 25-30% EtOAc/light petroleum gave foreruns; then further elution with 33-40% EtOAc/light petroleum gave 8 (97 mg, 66%): mp (CH 2Cl2/hexane) 174-175.5 °C; 1 28.64 (q, 3 C, C(CH3)3). Anal.…”

Section: N-(7-amino-3-phenyl-16-naphthyridin-2-yl)-n′-tert-butylurea ...mentioning

confidence: 99%

“…(11). Similar reaction of a stirred solution of 3-(2,6-dichlorophenyl)-1,6-naphthyridine-2,7-diamine 23 (9) (100 mg, 0.328 mmol) in dry DMF (5 mL) with 60% NaH (16 mg, 0.40 mmol) under N2 at 20 °C for 10 min, then with a solution of tert-butyl isocyanate (45 µL, 0.395 mmol) in dry DMF (1 mL) at 20 °C for 1 h, followed by chromatography of the resulting product on silica gel (eluting with 0.25-0.5% MeOH/CH 2Cl2) gave 11 ( 28.64 (q, 3 C, C(CH3)3). Anal.…”

Section: N-(7-amino-3-phenyl-16-naphthyridin-2-yl)-n′-tert-butylurea ...mentioning

confidence: 99%

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3-(3,5-Dimethoxyphenyl)-1,6-naphthyridine-2,7-diamines and Related 2-Urea Derivatives Are Potent and Selective Inhibitors of the FGF Receptor-1 Tyrosine Kinase

et al. 2000

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A series of 3-aryl-1,6-naphthyridine-2,7-diamines and related 2-ureas were prepared and evaluated as inhibitors of the FGF receptor-1 tyrosine kinase. Condensation of 4,6-diaminonicotinaldehyde and substituted phenylacetonitriles gave intermediate naphthyridine-2,7-diamines, and direct reaction of the monoanion of these (NaH/DMF) with alkyl or aryl isocyanates selectively gave the 2-ureas in varying yields (23-93%). For the preparation of more soluble 7-alkylamino-2-ureas, a number of protecting groups for the 2-amine were evaluated (phthaloyl, 4-methoxybenzyl) following selective blocking of the 7-amine (trityl), but these were not superior to the (required) 2-tert-Bu-urea group itself. Direct alkylation of the anion of the (unprotected) 7-amino group with excess 4-(3-chloropropyl)morpholine in DMF gave low (10%) yields of the desired product, but alkylation of the 7-acetamido anion, followed by mild alkaline hydrolysis, raised this to 64%. 3-Phenyl analogues were nonspecific inhibitors of isolated c-Src, FGFR, and PDGFR tyrosine kinases, whereas 3-(2,6-dichlorophenyl) analogues were most effective against c-Src and FGFR, and 3-(3,5-dimethoxyphenyl) derivatives showed high selectivity for FGFR alone. A water-soluble (7-morpholinylpropylamino) analogue retained high FGFR potency (IC(50) 31 nM) and selectivity. Pairwise comparison of the 1, 6-naphthyridines and the corresponding known pyrido[2,3-d]pyrimidine analogues showed little differences in potency or patterns of selectivity, suggesting that the 1-aza atom of the latter is not important for activity. A 7-acetamide derivative inhibited the growth of FGFR-expressing tumor cell lines and was particularly potent against HUVECs (IC(50) 4 nM). This compound was also a very potent inhibitor of HUVEC microcapillary formation (IC(50) 0.01 nM) and Matrigel invasion (IC(50) 7 nM) and showed significant in vivo antitumor effects in a highly vascularized mammary adenocarcinoma 16/c model at nontoxic doses. The compounds are worthy of further evaluation as antiangiogenesis agents.

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