Synthesis of nitrosourea derivatives of pyridine and piperidine as potential anticancer agents

Abstract

Nitrosourea derivatives 18-22 which utilize either a piperidine or pyridine ring as a carrier group were synthesized and evaluated for anticancer activity. N'-(1-Benzyl-4-piperidinyl)-N-(2-chloroethyl)-N-nitosourea hydrogen maleate (19) exhibited good activity against intracranial L1210 leukemia as well as the mouse ependymoblastoma brain tumor system. Compound 19 exhibited comparable activity in the Lewis lung carcinoma system to N,N'-bis(2-chloroethyl)-N-nitrosourea. Replacement of the N-benzyl group in both the 3-piperidinyl- and 4-piperidinylnitrosoureas resulted in less active compounds in all tumor systems tested. The 3-pyridylnitrosourea 22 was inactive in the L-1210 leukemia system.

Pd-Catalyzed Amidations of Aryl Chlorides Using Monodentate Biaryl Phosphine Ligands: A Kinetic, Computational, and Synthetic Investigation

“…Mp = 104-105 o C (lit. [26] 3-Formylaminopyridine (Table 3, Entry 2). [27] Using the general procedure, 3-chloropyridine (95 µL, 1.0 mmol), formamide (60 µL, 1.5 mmol), Pd 2 dba 3 (9.2 mg, 10 µmol), L6 (24.0 mg, 50 µmol), K 3 PO 4 (318 mg, 1.5 mmol) in t-BuOH (2.0 mL) were allowed to react at 110 o C for 8 h.…”

Crystal Structure of 4-(2-chloroacetamido)pyridinium chloride monohydrate, C7H10Cl2N2O2

“…Combining a pyridinium chloride sca old with the biologically active 2-chloroacetamide moiety has received great attention as antineoplastic [2][3][4]. Also, acetamide derivatives have been reported as antitumor activity [5].…”

A Critical Appraisal of the Evolution ofN-Nitrosoureas as Anticancer Drugs

“…Several N -nitrosourea derivatives of N -alkylated piperidines 273 − 276 (Table ) were of interest because (1) they are nitrogen analogues of CCNU ( 137b ), (2) they can be isolated as stable, water-soluble crystalline salts, (3) the N -substituent can be altered to vary the lipophilicities of the compounds, and (4) they are less leukopenic than BCNU ( 33 ) at equitoxic doses. Representative syntheses 246 of 273 and 276 are shown in Scheme a,b.…”