5'-O-Alkyl-5-fluorouridines: Synthesis and biological activity

1987 ◽  
Vol 52 (6) ◽  
pp. 1589-1608 ◽  
Author(s):  
Antonín Holý ◽  
Joachim König ◽  
Jiří Veselý ◽  
Dieter Cech ◽  
Ivan Votruba ◽  
...  
Keyword(s):  
Sodium Hydride ◽  
Alkyl Halides ◽  
Leukemic Cells ◽  
Elemental Fluorine ◽  
Subsequent Hydrolysis ◽  
Vesicular Stomatitis ◽  
L 1210 Leukemia ◽  
Derivatives Of ◽  
Allyl Derivative ◽  
Tin Tetrachloride

Methyl 2,3-O-isopropylidene-D-ribofuranoside (IV) was alkylated with alkyl halides in the presence of sodium hydride and the products were transformed by acid hydrolysis and glycosylation into methyl 5-O-alkyl-D-ribofuranosides VII. Benzoylation of VII followed by acetolysis afforded 1-O-acetyl-2,3-di-O-benzoyl-5-O-alkyl-D-ribofuranoses IX which on reaction with 2,4-bis(trimethylsilyloxy)pyrimidine in the presence of tin tetrachloride in acetonitrile and subsequent hydrolysis gave 5'-O-alkyl-2',3'-di-O-benzoyluridines XIa-XIe. Methanolysis of compounds XI furnished 5'-O-alkyluridines III. The 5-O-allyl derivative XII was hydroxylated in the presence OsO4 and transformed further to 5'-O-(RS)-(2,3-dihydroxypropyl)uridine (IIIg) and its tetrabenzoate XVI. Compounds XI and XVI on reaction with elemental fluorine in acetic acid afforded benzoyl derivatives of 5'-O-alkyl-5-fluorouridines XVIIa-XVIIe and XIX which were methanolyzed to give 5'-O-alkyl-5-fluorouridines II. This procedure afforded 5'-O-methyl (IIa), ethyl (IIb), n-butyl (IIc), n-hexyl (IId), n-octyl (IIe), and (RS)-(2,3-dihydroxypropyl) (IIf) derivatives of 5-fluorouridine. None of the compounds II exhibited antibacterial effect on Escherichia coli B or antiviral activity against HSV-1, HSV-2, vaccinia virus or vesicular stomatitis viruses. Compounds IIc,d,e suppressed the growth of L 1210 mice leukemic cells at concentrations of 10-5 to 10-6 mol l-1; the 5'-O-n-butyl derivative IIc has the highest activity (ID50 2·8 μmol l-1) but does not prolong the life span of L 1210 leukemia bearing mice following repeated daily doses of 80 mg/kg.

Synthesis and Biological Effects of N-(2-Phosphonomethoxyethyl) Derivatives of Deazapurine Bases

1993 ◽  
Vol 58 (6) ◽  
pp. 1419-1429 ◽  
Author(s):  
Hana Dvořáková ◽  
Antonín Holý
Keyword(s):  
Biological Effects ◽  
Sodium Hydride ◽  
Cesium Carbonate ◽  
Cytostatic Effect ◽  
Phosphonic Acids ◽  
Dna Viruses ◽  
Purine Bases ◽  
Heterocyclic Bases ◽  
L 1210 Leukemia ◽  
Derivatives Of

Analogs of antiviral 9-(2-phosphonomethoxyethyl)adenine (PMEA,II), containing modified purine bases 1-deazaadenine (VII, 3-deazapurine (XI), 7-deaza-7-cyanoadenine (XIIIb) and 3-deazaguanine (XXIb) were prepared by alkylation of the heterocyclic bases with bis(2-propyl) 2-chloroethoxymethylphosphonate (V) in dimethylformamide in the presence of sodium hydride or cesium carbonate. The obtained protected derivatives were deblocked with bromotrimethylsilane to give the phosphonic acids. 3-DeazaPMEG (XXIb) is active against DNA viruses and exhibits a marked cytostatic effect against L-1210 leukemia.

Preparation of 2'(3')-O-phosphonylmethyl derivatives of ribonucleosides

1983 ◽  
Vol 48 (3) ◽  
pp. 778-789 ◽  
Author(s):  
Ivan Rosenberg ◽  
Antonín Holý
Keyword(s):  
Alkali Metal ◽  
Metal Hydride ◽  
Sodium Hydride ◽  
Protecting Groups ◽  
Aqueous Alkali ◽  
Subsequent Hydrolysis ◽  
Derivatives Of ◽  
Alkali Metal Hydride

Reaction of 5'-O-tritylribonucleosides I with dimethyl p-toluenesulfonyloxymethanephosphonate (III) followed by hydrolysis afforded 2'(3')-O-phosphonylmethyluridine (IIa), -cytidine (IIb) and -adenosine (IIc). With 2',5'-di-O-trityluridine (IX), this procedure led to the 3'-isomer of IIa, with 3',5'-di-O-trityluridine (X) to the 2'-isomer. 5'-O-Trityluridine (Ia) and -cytidine (Ib) were converted by reaction with iodomethanephosphonic acid and N,N'-dicyclohexylcarbodiimide into the 2'(3')-O-iodomethanephosphonyl derivatives IVa, b which on reaction with sodium hydride and subsequent hydrolysis gave the compounds IIa and IIb. Reaction of compound I or 5'-O-benzoyluridine (VIII) with chloromethanephosphonyl dichloride (V) and removal of the protecting groups afforded 2'(3')-O-chloromethanephosphonylribonucleosides VI which on reaction with sodium hydride, or better with aqueous alkali, gave 2'(3')-O-phosphonylmethyl derivatives of uridine (IIa), cytidine (IIb), adenosine (IIc) and guanosine (IId). 2',3'-O-Isopropylideneribonucleosides XI reacted with the compound V to give, after hydrolysis, 5'-O-chloromethanephosphonyluridine (XIIa) and cytidine (XIIb). These compounds were not affected by an alkali metal hydride or hydroxide.

scholarly journals 2-Phenitidine derivatives as suitable inhibitors of butyrylcholinesterase

2013 ◽  
Vol 49 (1) ◽  
pp. 127-133
Author(s):  
Muhammad Athar Abbasi ◽  
Aziz-ur-Rehman ◽  
Muhammad Zahid Qureshi ◽  
Farhan Mehmood Khan ◽  
Khalid Mohmmed Khan ◽  
...  
Keyword(s):  
Infrared Spectroscopy ◽  
Benzoyl Chloride ◽  
Acetyl Chloride ◽  
Sulfonyl Chloride ◽  
Sodium Hydride ◽  
Alkyl Halides ◽  
H Nmr ◽  
Derivatives Of

This manuscript reports the synthesis of a series of N-substituted derivatives of 2-phenitidine. First, the reaction of 2-phenitidine (1) with benzene sulfonyl chloride (2) yielded N-(2-ethoxyphenyl) benzenesulfonamide (3), which further on treatment with sodium hydride and alkyl halides (4a-g) furnished into new sulfonamides (5a-g). Second, the phenitidine reacted with benzoyl chloride (6) and acetyl chloride (8) to yield the reported N-benzoyl phenitidine (7) and N-acetyl phenitidine (9), respectively. These derivatives were characterized by infrared spectroscopy, ¹H-NMR, and EI-MS, and then screened against acetylcholinesterase, butylcholinesterase, and lipoxygenase enzyme, and were found to be potent inhibitors of butyrylcholinesterase alone.

scholarly journals CHEMISTRY AND SYNTHESIS OF SOME DIHYDRO-2H-l,4-BENZOTHIAZINE DERIVATIVES

1966 ◽  
Vol 44 (11) ◽  
pp. 1247-1258 ◽  
Author(s):  
Raj Nandan Prasad ◽  
Karin Tietje
Keyword(s):  
Alkyl Halides ◽  
Reduction Product ◽  
Alkyl Derivatives ◽  
Reaction Proceeds ◽  
Thiazine Ring ◽  
Derivatives Of ◽  
Compound Xviii ◽  
Acyl Derivatives

The formation of 3-oxo-3,4-dihydro-2H-1,4-benzothiazine (IIIa) by cyclization of alkyl 2-haloacetamidophenyl sulfides (I) was investigated; it is proposed that the reaction proceeds via a six-membered sulfonium halide. The preparation of 4-alkyl derivatives of IIIa and of 4-alkyl and 4-acyl derivatives of its reduction product 3,4-dihydro-2H-1,4-benzothiazine (Va) is described. Acylation of Va was shown to proceed without opening of the thiazine ring. Preparation of the O-benzoyl, N-benzoyl, and O,N-dibenzoyl derivatives of 2-(β-hydroxyethyl-mercapto)aniline (VIII) has permitted clarification of the confusion in the literature with respect to the derivatives of Va and VIII. Compound XVIII, the 1,1-dioxide of IIIa, undergoes C-alkylation at the 2-position when treated with alkyl halides, rather than O-alkylation as previously suggested.

Pyrimidine Acyclic Nucleotide Analogues with Aromatic Substituents in C-5 Position

2007 ◽  
Vol 72 (7) ◽  
pp. 927-951 ◽  
Author(s):  
Marcela Krečmerová ◽  
Antonín Holý ◽  
Milena Masojídková
Keyword(s):  
Antiviral Activity ◽  
Cell Cultures ◽  
Inhibitory Activity ◽  
Thymidine Phosphorylase ◽  
Sodium Hydride ◽  
Phosphonic Acids ◽  
Nucleotide Analogues ◽  
Varicella Zoster ◽  
Subsequent Hydrolysis ◽  
Phosphonate Esters

NH2-protected 5-phenylcytosine and its derivatives 2a-2d were treated with (2S)-2-[(trityloxy)methyl]oxirane (3) followed by etherification with diisopropyl [(tosyloxy)methyl]phosphonate (5) in the presence of sodium hydride. The intermediary phosphonate esters 6 were debenzoylated and subsequently transformed to free phosphonic acids, i.e. (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-phenylcytosine (5-phenyl-HPMPC) derivatives (8a-8d) by the action of bromotrimethylsilane and subsequent hydrolysis. Deamination of these compounds with 3-methylbutyl nitrite afforded corresponding (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-phenyluracil (5-phenyl-HPMPU) derivatives (9a-9d). R-Enantiomers 14 and 15 were prepared analogously starting from (2R)-2-[(trityloxy)methyl]oxirane. 5-Benzyl-, 5-[(1-naphthyl)methyl]- and 5-[(2-naphthyl)methyl]HPMPU (24a-24c) and -HPMPC (25a-25c) were synthesized from appropriate 5-arylmethyl-4-methoxypyrimidin-2(1H)-ones similarly as described for 5-phenyl derivatives. Antiviral activity was found for (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-phenyluracil (9a) (HSV-1 and HSV-2) and (R)-1-[3-hydroxy2-(phosphonomethoxy)propyl]-5-phenylcytosine (14) (cytomegalovirus and varicella-zoster virus), both tested in cell cultures. Some of the 5-phenyluracil derivatives possessed inhibitory activity against thymidine phosphorylase from SD-lymphoma.

Hydrazine derivatives. III. A study of alkylation of guanazole

1976 ◽  
Vol 54 (22) ◽  
pp. 3620-3625 ◽  
Author(s):  
José J. Fuentes ◽  
Jacques A. Lenoir
Keyword(s):  
Aqueous Media ◽  
Alkyl Halides ◽  
Hydrazine Derivatives ◽  
Derivatives Of

Spectroscopic results from mono- and dibenzylidene derivatives of 1-alkylguanazoles establish that alkylation of 3,5-diamino-1,2,4-triazole (guanazole) with alkyl halides in basic non-aqueous media occurs at position N-1.

Notizen: The Synthesis of a New Fused Thiazolo [4,3-c] -1,2,4-triazole System and its Derivatives

1976 ◽  
Vol 31 (6) ◽  
pp. 853-856 ◽  
Author(s):  
Nazmi Abd Elatif Kassab ◽  
Sanaa Osman Abd Allah ◽  
Hamed Abdel Reheem Ead
Keyword(s):  
Potassium Salt ◽  
Aromatic Aldehydes ◽  
Alkyl Halides ◽  
Formaldehyde Solution ◽  
Derivatives Of

Cyclisation of the 4-phenylhydrazono derivatives of 2-thiazolidinone or 2-thiazolidinethione (1) with formaldehyde solution or with aromatic aldehydes yields 2-phenyl-2,3-dihydrothiazolo[4,3-c]-1,2,4-triazol-5-one or its 5-thiocarbonyl analogue (2). Condensing 2 with aromatic aldehydes afforded the corresponding 7-arylidene derivatives (8).The 5-arylidene derivatives of 4-anisylimino-2-thiazolidinethione (5) were obtained by condensing 4 with aromatic aldehydes. The potassium salt of 5 reacts readily with alkyl halides to yield the 5-arylidene derivatives of 4-anisylimino-2-alkylmercapto-2-thiazoline (6).

The cleavage of aryl-metal bonds by elemental fluorine: synthesis of aryl-fluorides

1983 ◽  
Vol 61 (4) ◽  
pp. 658-660 ◽  
Author(s):  
Michael J. Adam ◽  
Joffre M. Berry ◽  
Laurance D. Hall ◽  
Brian D. Pate ◽  
Thomas J. Ruth
Keyword(s):  
Aromatic Compounds ◽  
Metal Substrate ◽  
Rapid Synthesis ◽  
Elemental Fluorine ◽  
Tin Compounds ◽  
Radiochemical Yields ◽  
Germanium Silicon ◽  
Metal Bonds ◽  
Derivatives Of ◽  
General Method

The reaction of elemental fluorine with phenyl derivatives of tin, lead, germanium, silicon, mercury, and thallium has been studied with the aim of developing a general method for labelling aromatic compounds with radioactive 18F. Rapid synthesis of fluorobenzene was achieved in varying chemical yields up to 70%, depending largely upon the metal substrate used, with aryl–tin compounds giving the highest yields. Radiochemical yields are also given for the synthesis of 18F-fluorobenzene from the cleavage of aryl–tin bonds with 18F-F2.

Sign in / Sign up

Export Citation Format

Share Document