Sorivudine

Modify Date: 2024-01-11 22:23:38

Sorivudine Structure
Sorivudine structure
Common Name Sorivudine
CAS Number 77181-69-2 Molecular Weight 349.13500
Density 1.979g/cm3 Boiling Point N/A
Molecular Formula C11H13BrN2O6 Melting Point 182 °C
MSDS N/A Flash Point N/A

 Use of Sorivudine


Sorivudine (BV-araU) is an orally active synthetic pyrimidine nucleoside antimetabolite drug. Sorivudine derives its antiviral activity from selective conversion by a specific thymidine kinase present in certain DNA viruses to nucleotides, which can in turn interfere with viral DNA synthesis[1].

 Names

Name Sorivudine
Synonym More Synonyms

 Sorivudine Biological Activity

Description Sorivudine (BV-araU) is an orally active synthetic pyrimidine nucleoside antimetabolite drug. Sorivudine derives its antiviral activity from selective conversion by a specific thymidine kinase present in certain DNA viruses to nucleotides, which can in turn interfere with viral DNA synthesis[1].
Related Catalog
In Vitro Sorivudine (BV-araU) inhibits strains of HSV-1 and HSV-2 (wild-type strains VR-3 and UW-268) with ID50s (50% inhibitory dose) of 0.39 and 0.67 μM, respectively[1]. Sorivudine has antiviral activity against several viruses including varicella zoster virus, herpes simplex type 1 virus, and Epstein-Barr virus[1]. Sorivudine (BV-araU) is a pyrimidine nucleoside analog which has in vitro inhibitory activity against varicella zoster virus (VZV) at concentrations of 00001-0.004 mg/ml These concentrations are over 1000-fold lower than those which are required for the inhibition of VZV replication by acyclovir 3 Sorivudine also inhibits HSV-I replication at concentrations ranging from 0.03-0.1 mg/ml[2].
In Vivo Sorivudine (BV-araU) has been evaluated in the treatment of HSV-l encephalitis when administered orally to mice. At dosages in excess of 12.5 mg/kg, survival of treated mice is prolonged. With doses in excess of 50 mg/kg, a significant decrease in mortality was achieved as we1l. A more relevant model is that of simian varicella virus infection in African green monkeys (Cerophithecus aethiops). In this system, Sorivudine therapy at dosages as low as 20 mg/kg per day given intramuscularly or 100 mg/kg per day administered orally completely protected against viremia and mortality. In the conduct of these studies, there was no evidence of neurotoxicity or abnormalities in hematology or clinical chemistries. Doses as low as 0.2 mg/kg per day were effective; however, breakthrough viremia was noted at lower dosages[2].
References

[1]. Diasio RB, et al. Sorivudine and 5-fluorouracil; a clinically significant drug-drug interaction due to inhibition of dihydropyrimidine dehydrogenase. Br J Clin Pharmacol. 1998 Jul;46(1):1-4.

[2]. Whitley RJ, et al. Sorivudine: a potent inhibitor of varicella zoster virus replication.Adv Exp Med Biol. 1996;394:41-4.

 Chemical & Physical Properties

Density 1.979g/cm3
Melting Point 182 °C
Molecular Formula C11H13BrN2O6
Molecular Weight 349.13500
Exact Mass 347.99600
PSA 124.78000
Index of Refraction 1.746
Storage condition 2-8°C

 Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :
UV9009810
CHEMICAL NAME :
2,4(1H,3H)-Pyrimidinedione, 1-beta-D-arabinofuranosyl-5-(2-bromoethenyl)-, (E)-
CAS REGISTRY NUMBER :
77181-69-2
LAST UPDATED :
199503
DATA ITEMS CITED :
15
MOLECULAR FORMULA :
C11-H13-Br-N2-O6
MOLECULAR WEIGHT :
349.17

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
>8 gm/kg
TOXIC EFFECTS :
Gastrointestinal - other changes
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intraperitoneal
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
>2 gm/kg
TOXIC EFFECTS :
Behavioral - altered sleep time (including change in righting reflex) Kidney, Ureter, Bladder - other changes in urine composition
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Subcutaneous
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
>2 gm/kg
TOXIC EFFECTS :
Behavioral - altered sleep time (including change in righting reflex) Kidney, Ureter, Bladder - other changes in urine composition
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
>10 gm/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intraperitoneal
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
>3 gm/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Subcutaneous
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
>5 gm/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
TYPE OF TEST :
LD - Lethal dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Mammal - dog
DOSE/DURATION :
>5 gm/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
72800 mg/kg/26W-C
TOXIC EFFECTS :
Liver - other changes Endocrine - hyperglycemia Blood - changes in cell count (unspecified)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
112 gm/kg/4W-I
TOXIC EFFECTS :
Liver - changes in liver weight Kidney, Ureter, Bladder - changes in bladder weight Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Mammal - dog
DOSE/DURATION :
45 gm/kg/4W-C
TOXIC EFFECTS :
Cardiac - EKG changes not diagnostic of specified effects
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Mammal - dog
DOSE/DURATION :
182 gm/kg/26W-C
TOXIC EFFECTS :
Endocrine - other changes Blood - changes in spleen Related to Chronic Data - death
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
22 gm/kg
SEX/DURATION :
female 7-17 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - other developmental abnormalities
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
500 mg/kg
SEX/DURATION :
female 17-20 day(s) after conception lactating female 21 day(s) post-birth
TOXIC EFFECTS :
Reproductive - Effects on Newborn - live birth index (measured after birth)
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Oral
DOSE :
1625 mg/kg
SEX/DURATION :
female 6-18 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetal death

MUTATION DATA

TYPE OF TEST :
Sister chromatid exchange
TEST SYSTEM :
Human Lymphocyte
DOSE/DURATION :
200 mg/L
REFERENCE :
LIFSAK Life Sciences. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1-8, 1962-69; V.14- 1974- Volume(issue)/page/year: 38,281,1986

 Synthetic Route

~22%

Sorivudine Structure

Sorivudine

CAS#:77181-69-2

Literature: RESprotech GmbH Patent: US2010/227834 A1, 2010 ; Location in patent: Page/Page column 20 ;

~%

Sorivudine Structure

Sorivudine

CAS#:77181-69-2

Literature: Baraldi, Pier G.; Bazzanini, Rita; Manfredini, Stefano; Simoni, Daniele; Robins, Morris J. Tetrahedron Letters, 1993 , vol. 34, # 19 p. 3177 - 3180

~%

Sorivudine Structure

Sorivudine

CAS#:77181-69-2

Literature: Baraldi, Pier G.; Bazzanini, Rita; Manfredini, Stefano; Simoni, Daniele; Robins, Morris J. Tetrahedron Letters, 1993 , vol. 34, # 19 p. 3177 - 3180

~%

Sorivudine Structure

Sorivudine

CAS#:77181-69-2

Literature: Robins; Manfredini Tetrahedron Letters, 1990 , vol. 31, # 39 p. 5633 - 5636

 Precursor & DownStream

Precursor  2

DownStream  0

 Synonyms

Bravavir
Bravavir (tn)
Sorivudin
YN-72
Brovavir
BV-araU