Dihydrouridine 5627-05-4

Dihydrouridine (abbreviated as DDHU, or UH2) is a pyrimidine which is the result of adding two hydrogen atoms to a uridine, making it a fully saturated pyrimidine ring with no remaining double bonds. D is found in tRNA and rRNA molecules as a nucleoside; the correspondingnucleobase is 5,6-dihydrouracil.

Because it is non-planar, D disturbs the stacking interactions in helices and destabilizes the RNA structure. D also stabilizes the C2’-endo sugar conformation, which is more flexible than the C3’-endo conformation, and this effect is propagated to the 5’-neighboring residue. Thus, whilepseudouridine and 2’-O-methylations stabilize the local RNA structure, D does the opposite.[1]

tRNA of organisms that grow at low temperatures (psychrophiles) have high 5,6-dihydrouridine levels (40-70% more on average) which provides the necessary, local, flexibility of the tRNA at or below the freezing poin

Dihydrouridine
Identifiers
CAS number 5627-05-4
PubChem 94312
Jmol-3D images Image 1
Properties
Molecular formula C9H14N2O6
Molar mass 246.217 g/mol

Dihydrouracil 504-07-4

Dihydrouracil is an intermediate in the catabolism of uracil.

Identifiers
CAS number 504-07-4
PubChem 649
MeSH Dihydrouracil
Jmol-3D images Image 1
Properties
Molecular formula C4H6N2O2
Molar mass 114.10264

Dihydrothymine 696-04-8

Dihydrothymine is an intermediate in the metabolism of thymine.

Dihydrothymine
Identifiers
CAS number 696-04-8
PubChem 93556
MeSH 5,6-dihydrothymine
Jmol-3D images Image 1
Properties
Molecular formula C5H8N2O2
Molar mass 128.12922

Deoxyuridine 951-78-0

Deoxyuridine is a compound and a nucleoside. It is similar in chemical structure to uridine, but without the 2′-hydroxyl group.

Idoxuridine and Trifluridine are variants of deoxyuridine used as antiviral drugs. They are similar enough to be incorporated as part of DNA replication, but they possess side groups on the uracil component (an iodine and a CF3 group, respectively), that prevent base pairing.

Deoxyuridine
Identifiers
CAS number 951-78-0 Yes
PubChem 640
ChemSpider 13118 Yes
UNII W78I7AY22C Yes
MeSH Deoxyuridine
ChEBI CHEBI:16450 
ChEMBL CHEMBL353955 
Jmol-3D images Image 1
Properties
Molecular formula C9H12N2O5
Molar mass 228.202

Clevudine 69256-17-3

Clevudine (INN) is an antiviral drug for the treatment of hepatitis B. Clevudine is already approved for HBV in South Korea and the Philippines. It is marketed by Bukwang pharmaceuticals in South Korea under the tradenames Levovir and Revovir. Under license from Bukwang, Pharmasset was developing the drug, but its phase III clinical trial (international, multicenter, randomized, double-blind, 96 week QUASH studies) was terminated due to some myopathy cases in patients.

Systematic (IUPAC) name
1-[(2S,3R,4S,5S)-3-fluoro-4-hydroxy-5- (hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine- 2,4-dione
Clinical data
Pregnancy cat.  ?
Legal status  ?
Routes Oral
Identifiers
CAS number 69256-17-3 Yes
ATC code J05AF12 [1]
PubChem CID 73115
ChemSpider 65894
UNII IN51MVP5F1 
KEGG D03537 Yes
ChEMBL CHEMBL458875 
Chemical data
Formula C10H13FN2O5 
Mol. mass 260.219 g/mol

It is a nucleoside analog

Carmofur

Carmofur (INN) or HCFU (1-hexylcarbamoyl-5-fluorouracil) is a pyrimidine analogue used as an antineoplastic agent. It is a derivative offluorouracil.

Systematic (IUPAC) name
5-fluoro-N-hexyl-2,4-dioxo-pyrimidine-1-carboxamide
Clinical data
AHFS/Drugs.com International Drug Names
Pregnancy cat.  ?
Legal status  ?
Routes Oral
Identifiers
CAS number 61422-45-5 Yes
ATC code L01BC04
PubChem CID 2577
ChemSpider 2479 
UNII HA82M3RAB2 
Synonyms 1-hexylcarbamoyl-5-fluorouracil
Chemical data
Formula C11H16FN3O3 
Mol. mass 257.261 g/mol

Uses

Breast Cancer

Colorectal Cancer

Carmofur, in its oral form, has also been used as adjuvant chemotherapy for curatively resected colorectal cancer patients. Trials and meta-analyses have confirmed that the drug is effective on patients with this cancer type, extending their survival.[1]

Adverse effects

As fluorouracil, carmofur has been known to induce leukoencephalopathy

5-Bromouracil

5-Bromouracil
Identifiers
Abbreviations 5-BrU
5-BU
CAS number 51-20-7 Yes
PubChem 5802
ChemSpider 5597 Yes
ChEBI CHEBI:20552 Yes
ChEMBL CHEMBL144730 Yes
Jmol-3D images Image 1
Properties
Molecular formula C4H3BrN2O2
Molar mass 190.983 g/mol
 Yes (verify) (what is: Yes/?)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)

5-Bromouracil (or 5-bromo-2,4(1H,3H)-pyrimidinedione or 5-BrU or 5-BU) is a brominated derivative of uracil that acts as an antimetabolite or base analog, substituting for thymine in DNA, and can induce DNA mutation in the same way as 2-aminopurine. It is used mainly as an experimentalmutagen, but its deoxyriboside derivative (5-bromo-2-deoxy-uridine) is used to treat neoplasms.

5-BrU exists in three tautomeric forms that have different base pairing properties. The keto form (shown in the infobox) is complementary toadenine, so it can be incorporated into DNA by aligning opposite adenine residues during DNA replication (see below left). Alternatively, theenol (below right) and ion forms are complementary to guanine. This means that 5-BrU can be present in DNA either opposite adenine or guanine.

5-Bromouracil bp.svg

The three forms frequently interchange so base-pairing properties can become altered at any time. The result of this is that during a subsequent round of replication a different base is aligned opposite the 5-BrU residue. Further rounds of replication ‘fix’ the change by incorporating a normal nitrogen base into the complementary strand.

Thus 5-BrU induces a point mutation via base substitution. This base pair will change from an A-T to a G-C or from a G-C to an A-T after a number of replication cycles, depending on whether 5-BrU is within the DNA molecule or is an incoming base when it is enolized or ionized.

Bromodeoxyuridine

Identifiers
CAS number 59-14-3 Yes
PubChem 6918942
ChemSpider 5294121 Yes
UNII G34N38R2N1 Yes
MeSH Bromodeoxyuridine
ChEMBL CHEMBL222280 
Jmol-3D images Image 1
Properties
Molecular formula C9H11BrN2O5
Molar mass 307.098
  (verify) (what is: Yes/?)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)

Bromodeoxyuridine (5-bromo-2′-deoxyuridine, BrdU, BUdR, BrdUrd) is a synthetic nucleoside that is an analogue of thymidine. BrdU is commonly used in the detection of proliferating cells in living tissues.[1] 5-bromodeoxycytidine is deaminated to form BrdU.[2]

BrdU can be incorporated into the newly synthesized DNA of replicating cells (during the S phase of the cell cycle), substituting for thymidine during DNA replication. Antibodies specific for BrdU can then be used to detect the incorporated chemical (see immunohistochemistry), thus indicating cells that were actively replicating their DNA. Binding of the antibody requires denaturation of the DNA, usually by exposing the cells to acid or heat.[3]

BrdU can be passed to daughter cells upon replication.[4] BrdU has been demonstrated to be detectable over two years post-infusion.[5]

Because BrdU can replace thymidine during DNA replication, it can cause mutations, and its use is therefore potentially a health hazard.[3]However, because it is neither radioactive nor myelotoxic at labeling concentrations, it is widely preferred for in vivo studies of cancer cell proliferation.[6][7] However, at radiosensitizing concentrations, BrdU becomes myelosuppressive thus limiting its use for radiosensitizing.[2]

BrdU differs from thymidine in that BrdU substitutes a Br group for thymidine’s CH3 group. The Br substitution can be used in X-Ray diffraction experiments in crystals containing either DNA or RNA. The Br atom acts as an anomalous scatterer and its larger size will affect the crystal’s x-ray diffraction enough to detect isomorphous differences as well

Bromacil

Bromacil
Identifiers
CAS number 314-40-9 Yes
ChemSpider 9040 Yes
UNII I048FFR2J0 Yes
KEGG C10911 Yes
Jmol-3D images Image 1
Properties
Molecular formula C9H13BrN2O2
Molar mass 261.1157
Appearance Odorless, colorless to white, crystalline solid
Density 1.46 g/cm3
Melting point 157.5-160 degrees C

Bromacil is an organic compound with the chemical formula C9H13BrN2O2, commercially available as an herbicide, and also used as rat poison(Bromokill). Bromacil was first registered as a pesticide in the U.S. in 1961.[1] It is used for brush control and non-cropland areas.[2] It works by interfering with photosynthesis by entering the plant through the root zone and moving throughout the plant.[3] Bromacil is one of a group of compounds called substituted uracils. These materials are broad spectrum herbicides used for nonselective weed and brush control on non-croplands, as well as for selective weed control on a limited number of crops, such as citrus fruit and pineapple. [2] Bromacil is also found to be excellent at controlling perennial grasses.

Safety

There are quite a few safety precautions that should be taken when dealing with Bromacil. Dry formulations containing bromacil must bear the word “Caution” and liquid formulas must signal “Warning.” [2] Care should be exercised when spraying Bromacil on non-target plants because it will also stop the photosynthesis of the adjacent plants therefore killing them. Bromacil should never be used in residential or recreation areas for risk of exposure. Bromacil is slightly toxic if individuals accidentally eat or touch residues and practically nontoxic if inhaled. Bromacil is a mild eye irritant and a very slight skin irritant. It is not a skin sensitizer. [4] In studies using laboratory animals, bromacil is slightly toxic by the oral, dermal, and inhalation routes and has been placed in Toxicity Category IV (the lowest of four categories) for these effects. [1] This herbicide should be stored in a cool, dry place and after any handling a thorough hand-washing is advised.

Facts

Bromacil (40%) is combined with the active ingredient diuron in the herbicide Krovar, which is used by companies such as the Washington State Department of Transportation (WSDOT). It is in a group of chemicals that are absorbed through the gut and excreted primarily in the urine. Thehalf-life of bromacil in soils is about 60 days, but as long as 8 months in some conditions. [4] Bromacil is available in granular, liquid, water soluble liquid, and wettable powder formulations.[2] Because bromacil is a possible human carcinogen and systemic toxicity may result from intermediate exposure (one week to several months), EPA assessed risk to workers using several major exposure scenarios. Bromacil is stable tohydrolysis under normal environmental conditions.[1]

Applications

Bromacil is applied mainly by sprayers including boom, hand-held,knapsack, compressed air, tank-type, and power sprayers. Bromacil is also applied using aerosol, shaker, or sprinkler cans. Solid forms of bromacil are spread using granule applicators and spreaders. Application using aircraft is allowed only for Special Local Need registrations to control vegetation on the Department of Defense’s Yakima Firing Center in the state of Washington.[1]

Brivudine CAS No.69304-47-8

Systematic (IUPAC) name
5-[(E)-2-bromoethenyl]-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2,3,4-tetrahydropyrimidine-2,4-dione
Clinical data
AHFS/Drugs.com International Drug Names
Pregnancy cat. exclusion
Legal status  ?
Routes oral
Pharmacokinetic data
Bioavailability 30%
Half-life 16 hours
Excretion mainly renal
Identifiers
CAS number 69304-47-8 
ATC code J05AB15
PubChem CID 446727
ChemSpider 394011 Yes
UNII 2M3055079H Yes
ChEMBL CHEMBL31634 Yes
Chemical data
Formula C11H13BrN2O5 
Mol. mass 333.135 g/mol

History

Brivudine is a similar drug to acyclovir[clarification needed]. The compound was first synthesized by scientists at the University of Birmingham in the UK in the 1970s. It was shown to be a potent inhibitor of the herpes simplex virus Type 1 (HSV-1) as well as the varicella zoster virus (VZV) by Erik De Clercq at the Rega Institute for Medical Research in Belgium in 1979. In the 1980s the drug became commercially available in East Germany, where it was marketed as Helpin by a pharmaceutical company called Berlin-Chemie.

Approvals

Brivudine is approved for use in Germany and other European countries including Italy.

Mechanism of Action

Brivudine is an analogue of the nucleoside thymidine. The drug works because it is able to be incorporated into the viral DNA, but then blocks the action of DNA polymerases, thus inhibiting viral replication. The active compound is the 5′-triphosphate of BVDU, which is formed in subsequent phosphorylations by viral thymidine kinase and presumably by nucleoside diphosphate kinase.

The drug’s name

Brivudine derives from the drug’s chemical name of bromovinyldeoxyuridine or BVDU for short. The drug’s full chemical description is (E)-5-(2-bromovinyl)-2-deoxyuridine. It is also sold as Bridic, Brivox, Brivudin, Helpin, Zerpex, Zonavir and Zostex.

Suppliers

Brivudine main supplier is Berlin-Chemie, now part of Italy’s Menarini Group. The drug is approved for sale in Austria, Belgium, Germany, Greece, Italy, Luxembourg, Portugal and Spain. In Central America is provided Menarini Centro America and Wyeth.