5-Fluoro-uracil

Uracil, 6-dimethoxymethyl-3-methyl-2-thio-synthesis, 3, 113 Uracil, 1,3-dimethyl-dimers, 3, 74 Uracil, 3,6-dimethyl-synthesis, 3, 106, 110 Uracil, 5-fluoro-... 

Nl - URACIL, 5-FLUORO-l-(TETRAHYDRO-2-FURYLI- mtxt. with URACIL (114)... 

OCHg, SH, NHg, CHg, or COOH, ° adenine-thymine base pair - and its cationic and anionic forms (for the charge densities at C-5 and C-6 positions in uracil, thymine, 5-amino- 5-nitro- and 6-methyl-uracil, 6-azathymine and orotic acid, see refs. 187, 188) tt-HMO - -a-Del Re calculations on uracil, - 5-fluoro- and 5-bromouracil, 5,6-dihydrouracil and its anionic form tt-SCF MO -f a-Del Re... 

Uracil, 6-dimethoxymethyl-3-methyl-2-thio-synthesis, 3, 113 Uracil, 1,3-dimethyl-dimers, 3, 74 Uracil, 3,6-dimethyl-synthesis, 3, 106, 110 Uracil, 5-fluoro-as anticancer drug, I, 263 antineoplastic activity, 3, 152 as pharmaceutical, I, 159 reactions, 2, 59 synthesis, 3, 70 Uracil, 6-fluoro-hydrolysis, 3, 101 Uracil, 5-hydroxy-1,3-dimethyl-synthesis, 3, 133 Uracil, hydroxymethyl-oxidation, 3, 91... 

Direct bromination readily yields the 6-bromo derivative (111), just as with uracil. Analogous chlorination and iodination requires the presence of alkalies and even then proceeds in low yield. The 6-chloro derivative (113) was also obtained by partial hydrolysis of the postulated 3,5,6-trichloro-l,2,4-triazine (e.g.. Section II,B,6). The 6-bromo derivative (5-bromo-6-azauracil) served as the starting substance for several other derivatives. It was converted to the amino derivative (114) by ammonium acetate which, by means of sodium nitrite in hydrochloric acid, yielded a mixture of 6-chloro and 6-hydroxy derivatives. A modified Schiemann reaction was not suitable for preparing the 6-fluoro derivative. The 6-hydroxy derivative (115) (an isomer of cyanuric acid and the most acidic substance of this group, pKa — 2.95) was more conveniently prepared by alkaline hydrolysis of the 6-amino derivative. Further the bromo derivative was reacted with ethanolamine to prepare the 6-(2-hydroxyethyl) derivative however, this could not be converted to the corresponding 2-chloroethyl derivative. Similarly, the dimethylamino, morpholino, and hydrazino derivatives were prepared from the 6-bromo com-pound. ... 

C. Lipschitz, H. Iith, G. J. de Jong, U. A. Th Brinkman and R. W. Frei, Trace emich-ment of pyrimidine nucleobases, 5-fluoro-uracil and bromacil on a silver-loaded tliiol stationaty phase with on-line reversed-phase high-perfomance liquid cliromatography , J. Chromatogr. 471 321-334 (1989). 

Fluoro uracil mercury Tegafur Formaldehyde Biperiden Bronopol Cortivazol Edetate disodium Glaziovine Hexetidine Meptazinol Metampicillin sodium Methylol riboflavin Nifurfoline Nifurtoinol Noxytiolin Oxymetazoline HCI Phenindamine tartrate Pipebuzone Thihexinol Timonacic sodium Triclobisonium chloride T romethamine Tyloxapol Formamide Cimetide Primidone Protriptyline Razo xane Spiperone Formic acid Bupivacaine... 

Fluorouracil (5-fluorouracil, 5-FU, Fig. 5) represents an early example of rational drag design in that it originated from the observation that tumor cells, especially from gut, incorporate radiolabeled uracil more efficiently into DNA than normal cells. 5-FU is a fluorinated pyrimidine analog that must be activated metabolically. In the cells 5-FU is converted to 5-fluoro-2>deoxyuridine-monophosphate (FdUMP). This metabolite inhibits thymidilate synthase which catalyses the conversion of uridylate (dUMP) to thymidilate (dTMP) whereby methylenetetrahydrofo-late plays the role of the carbon-donating cofactor. The reduced folate cofactor occupies an allosteric site of... 

Methyl- C]thymine ([ C]FMAU) could be obtained in modest radiochemical yields via cross-coupling of [ CJmethyl iodide with l-(2 -deoxy-2 -fluoro-/3-D-arabinofuranosyl)-5-(trimethylstannyl)uracil. Optimal power was found to be 70W, since an increase to 100 W as well as a decrease to SOW resulted in lower radiochemical yields (Scheme 6). 

Verrumal (Hermal)-comb. numerous generics and combination preparations Efudix (Roche) Fluoro-uracile (Roche) generic... 

Different kinds of nucleosides (778) were prepared by condensation of compound 400 (see Section 11,3) with trimethylsilylated uracils under Lewis acid catalysis, and removal of one fluorine atom at C-2 of the sugars. Uridine 5 -(2-acetamido-2,4-dideoxy-4-fluoro-a-D-galactopyranosyl di-... 

Deoxy-3-fluoro- -D-xylofuranosyl)cytosine (821) was prepared by condensation of 2,5-di-0-benzoyl-3-deoxy-3-fluoro-D-xylofuranosyl bromide with bis(trimethylsilyl)cytosine (773). It was proposed that 1 -(3 1eoxy-3-fluoro-)S-D-arabinofuranosyl)uracil (823), prepared from l-(2,3-anhy-dro-)S-D-lyxofuranosyl)uracil (822) with anhydrous HF ( 8% in 1,4-dioxane 116 °, 41 h, 3% yield), has a twist conformation of the furanose ring(°r, acetone- 4-D20 . Jn-vf 13.5, Hz). Reexamination ... 

Efavirenz, nevirapine Epristeride, finasteride, dutasteride Fluoro uracil Leflunomide... 

Russian work confirms that cis- and fm s-[Pd(NH3) 2CI2] bind in the same manner to bases lacking a site of bi-dentate chelation. With 5-fluoro-uracil the ct s-isomer yields... 

Leichman CG, Lenz HJ, Leichman L et al. Quantitation of intratumoral thymidylate synthase expression predicts for disseminated colorectal cancer response and resistance to protracted-infusion fluoro-uracil and weekly leucovorin. J Clin Oncol 1997 15 3223-3229. 

The reaction of XeF2 with uracil produces the 5-fluoro derivative, which can be applied topically for treating some types of skin diseases including some types of skin cancer. The reaction producing 5-fluorouracil can be shown as... 

An interesting dinically useful prodrug is 5-fluorouracil, which is converted in vivo to 5-fluoro-2 -deoxyuridine 5 -monophosphate, a potent irreversible inactivator of thymidylate synthase It is sometimes charaderized as a dead end inactivator rather than a suicide substrate since no electrophile is unmasked during attempted catalytic turnover. Rathei since a fluorine atom replaces the proton found on the normal substrate enzyme-catalyzed deprotonation at the 5 -position of uracil cannot occur. The enzyme-inactivator covalent addud (analogous to the normal enzyme-substrate covalent intermediate) therefore cannot break down and has reached a dead end (R. R. Rando, Mechanism-Based Enzyme Inadivators , Pharm. Rev. 1984,36,111-142). 

The catalytic efficiency of this enzyme to hydrolyze 5-fluoro-5,6-dihydro-uracil was found to be approximately twice that toward 5,6-dihydrouracil [152], 2-Fluoro-/3-alanine can either be eliminated via the bile after conjugation with bile acids, or be converted to fluoroacetate (4.238) [153], The latter metabolite is transformed to fluorocitrate, a potent inhibitor of the aconi-tase-catalyzed conversion of citrate to isocitrate. This inhibition probably explains the clinical neurotoxicity of 5-fluorouracil [154] [155],... 

A number of l-aryl-6-aminouracils (LIX Ar = fluoro- or trifluoromethyl-substituted phenyl, X = H, NO or NHj) were found to possess antiviral activity against rhinovims 1059. Among these, l-(OT-trifluoromethylphenyl)-5,6-diamino-uracil (LIX Ar = W-CF3, X = NH2), possesses antibacterial activity against Bacillus subtilis, Staph, aureus zni Mycobacterium smegmatis [410]. 

O Connell MJ, Martenson JA, Wieand HS, et al. Improving adjuvant therapy for rectal cancer by combining protracted-infusion fluoro uracil with radiation therapy after curative surgery. N Engl J Med 1994 331 502-507. 

GITSG, A multi-institutional comparative trial of radiation therapy alone and in combination with 5 -fluoro uracil for locally unresectable pancreatic carcinoma. The Gastrointestinal T umor Study Group. Ann Surg 1979 189(2) 205-208. 

Eifel PJ, Morris M, Burke TW, et al. Preoperative continuous infusion cisplatinum and 5-fluoro-uracil with radiation for locally advanced or recurrent carcinoma of the vulva. Gynecol Oncol 1995 59 51-56. 

Thiol anions normally add reversibly to uracil derivatives <1991T4361>, although stable adducts can be isolated when the intermediate enolate is trapped with an added electrophile <2006JHC1095>. Thus, the addition of lithium phenylthiolate to 5-fluoro-l,3-dimethyluracil 457 in the presence of benzaldehyde gave a 46% yield of the adduct 458 as a mixture of only two diastereomers <2006JHC1095>. 

Aromatic compounds can participate in both [2+2] and [4+2] photocycloaddition reactions with uracil derivatives to give either benzocyclobutane or ethenoquinazoline (barrelene) derivatives, which can then undergo a number of subsequent photochemical reactions. The products obtained are dependent upon the reaction conditions, and thus the photocycloaddition reaction between naphthalenes 470 and l,3-dimethyl-5-fluorouracil 471 in cyclohexane gave 4a-fluoro-5,10-ethenobenzo[/]quinazolines 472 as products as a result of a [4+2] photocycloaddition (photo-Diels-Alder) reaction <2002TL3113, 2003H(61)377>. 

Rabdosia lasiocarpus (Flayata) Mao Guo Yan Ming Cao (whole plant) Terpenes, oridonin, rubescensins, 5-fluoro uracil.50 This herb is toxic. For carcinomas of esophagus and stomach, antiarthritic, antidotal, febrifuge. 

Fluoro-uracil Roche", Standardinformation Jiir Krankenhausapotheker Hoffmann-La Roche Grenzach-Whylcn, Ger. 1993. 

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