Endogenous Metabolite

This review article is an effort to summarize recent developments in researches providing uracil derivatives with promising biological potential. This article also aims to discuss potential future directions on the development of more potent and specific uracil analogues for various biological targets. Uracils are considered as privileged structures in drug discovery with a wide array of biological activities and synthetic accessibility. Antiviral and anti-tumour are the two most widely reported activities of uracil analogues however they also possess herbicidal, insecticidal and bactericidal activities. Their antiviral potential is based on the inhibition of key step in viral replication pathway resulting in potent activities against HIV, hepatitis B and C, the herpes viruses etc. Uracil derivatives such as 5-fluorouracil or 5-chlorouracil were the first pharmacological active derivatives to be generated. Poor selectivity limits its therapeutic application, resulting in high incidences of gastrointestinal tract or central nervous toxicity. Numerous modifications of uracil structure have been performed to tackle these problems resulting in the development of derivatives exhibiting better pharmacological and pharmacokinetic properties including increased bioactivity, selectivity, metabolic stability, absorption and lower toxicity. Researches of new uracils and fused uracil derivatives as bioactive agents are related with modifications of substituents at N(1), N(3), C(5) and C(6) positions of pyrimidine ring. This review is an endeavour to highlight the progress in the chemistry and biological activity of the uracils, predominately after the year 2000. In particular are presented synthetic methods and biological study for such analogues as: 5-fluorouracil or 5-chlorouracil derivatives, tegafur analogues, arabinopyranonucleosides of uracil, glucopyranonucleosides of uracil, liposidomycins, caprazamycins or tunicamycins, tritylated uridine analogues, nitro or cyano derivatives of uracil, uracil-quinazolinone, uracil-indole or uracil-isatin-conjugates, pyrimidinophanes containing one or two uracil units and nitrogen atoms in bridging polymethylene chains etc. In this review is also discussed synthesis and biological activity of fused uracils having uracil ring annulated with other heterocyclic ring[1].

Eur J Med Chem. 2015 Jun 5;97:582-611.

Uracil is a common and naturally occurring pyrimidine nucleobase in which the pyrimidine ring is substituted with two oxo groups at positions 2 and 4. Found in RNA, it base pairs with adenine and replaces thymine during DNA transcription. It has a role as a prodrug, a human metabolite, a Daphnia magna metabolite, a Saccharomyces cerevisiae metabolite, an Escherichia coli metabolite, a mouse metabolite and an allergen. It is a pyrimidine nucleobase and a pyrimidone. It is a tautomer of a (4S)-4-hydroxy-3,4-dihydropyrimidin-2(1H)-one.

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Uracil is a metabolite found in or produced by Escherichia coli (strain K12, MG1655).
Uracil is a natural product found in Hamigera avellanea, Paraphaeosphaeria minitans, and other organisms with data available.
Uracil is a metabolite found in or produced by Saccharomyces cerevisiae.
One of four nucleotide bases in the nucleic acid RNA.

C4H4N2O2

112.0868

112.03

C, 42.86; H, 3.60; N, 24.99; O, 28.55

66-22-8

66-22-8 (uracil); 3083-77-0 [1-beta-D-Arabinofuranosyluracil (Uracil 1-β-D-arabinofuranoside)]; 462-88-4 (Ureidopropionic acid); 504-07-4 (5,6-Dihydrouracil); 66-75-1 (Uramustine, Uracil mustard); 141-90-2 (2-Thiouracil); 58-96-8 (Uridin; β-Uridine)

1174

Typically exists as white to light yellow solids at room temperature

1.5±0.1 g/cm3

440.5±37.0 °C at 760 mmHg

330°C

220.2±26.5 °C

0.0±1.1 mmHg at 25°C

1.640

-2.55

65.72

O=C1NC(C=CN1)=O

ISAKRJDGNUQOIC-UHFFFAOYSA-N

InChI=1S/C4H4N2O2/c7-3-1-2-5-4(8)6-3/h1-2H,(H2,5,6,7,8)

Pyrimidine-2,4(1H,3H)-dione

2,4-Dioxopyrimidine; 2,4-Pyrimidinedione; Pirod; uracil; 66-22-8; 2,4-Dihydroxypyrimidine; 2,4(1H,3H)-Pyrimidinedione; pyrimidine-2,4(1H,3H)-dione; pyrimidine-2,4-diol; Pyrod; 2,4-Pyrimidinediol; Pyrod.

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 25 mg/mL (~223.04 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (22.30 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (22.30 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (22.30 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)