5-ヨード-2'-デオキシウリジン 化学特性,用途語,生産方法
外観
白色～ほとんど白色粉末～結晶
効能
抗ウイルス薬, DNAポリメラーゼ阻害薬
化学的特性
Crystalline Solid
使用
Idoxuridine is an antiviral agent effective against herpes-simplex infections; in ophthalmie eyedrops, ointments, and solutions.
適応症
Idoxuridine (Herplex) is a water-soluble iodinated derivative
of deoxyuridine that inhibits several DNA viruses
including HSV, VZV, vaccinia, and polyoma virus. The
triphosphorylated metabolite of idoxuridine inhibits
both viral and cellular DNA synthesis and is also incorporated
into DNA. Such modified DNA is susceptible to
strand breakage and causes aberrant viral protein synthesis.
Because of its significant host cytotoxicity, idoxuridine
cannot be used to treat systemic viral infections. The
development of resistance to this drug is common.
定義
ChEBI: A pyrimidine 2'-deoxyribonucleoside compound having 5-iodouracil as the nucleobase; used as an antiviral agent.
応用例（製薬）
A halogenated pyrimidine analog originally synthesized as an
anticancer agent. Formulated in dimethylsulfoxide for topical
application and as a solution for ophthalmic use.
Activity is largely limited to DNA viruses, primarily HSV-1,
HSV-2 and VZV. HSV-1 plaque formation in BHK 21 cells
is sensitive to 6.25–25 mg/L; type 2 microplaques required
62.5–125 mg/L. RNA viruses are not affected, with the exception
of oncogenic RNA viruses such as Rous sarcoma virus.
Drug resistance is easily generated in vitro, and may be an
obstacle to treatment. However, there is little or no crossresistance
with newer nucleoside analogs.
It is poorly soluble in water, and aqueous solutions are
ineffective against infections other than those localized to the
eye. In animals, therapeutic levels are achieved in the cornea
within 30 min of ophthalmic application and persist for 4 h.
Penetration is otherwise poor, with only the biologically inactive
dehalogenated metabolite uracil entering the eye.
The drug is too toxic for systemic administration. Contact
dermatitis, punctate epithelial keratopathy, follicular conjunctivitis,
ptosis, stenosis and occlusion of the puncta and keratinization
of the lid margins occur in up to 14% of those
receiving ophthalmic preparations.
It is used in herpes keratitis, but has largely been superseded
by trifluridine or aciclovir.
作用機序
Idoxuridine is a nucleoside containing a halogenated pyrimidine and is an analogue of thymidine. It
acts as an antiviral agent against DNA viruses by interfering with their replication based on the similarity
of structure between thymidine and idoxuridine. Idoxuridine is first phosphorylated by the host cell virusencoded enzyme thymidine kinase to an active triphosphate form. The phosphorylated drug inhibits
cellular DNA polymerase to a lesser extent than HSV DNA polymerase, which is necessary for the
synthesis of viral DNA. The triphosphate form of the drug is then incorporated during viral nucleic acid
synthesis by a false pairing system that replaces thymidine. When transcription occurs, faulty viral
proteins are formed, resulting in defective viral particles.
臨床応用
The only FDA-approved use of idoxuridine is in the
treatment of herpes simplex infections of the eyelid, conjunctiva conjunctiva,
and cornea. It is most effective against surface
infections because it has little ability to penetrate the tissues
of the eye. intravenous idoxuridine was designated
an orphan drug for the treatment of soft tissue sarcoma.
副作用
Idoxuridine may cause local irritation, mild edema, itching,
and photophobia. Corneal clouding and small punctate
defects in the corneal epithelium have been reported.
Allergic reactions are rare.
安全性プロファイル
Moderately toxic by
intraperitoneal route. Experimental
teratogenic and reproductive effects.
Questionable carcinogen with experimental
carcinogenic data. Human mutation data
reported. When heated to decomposition it
emits very toxic fumes of Iand NOx.
代謝
Idoxuridine is metabolized rapidly in the body to iodouracil, uracil, and iodide. Metabolites are excreted in the urine.
5-ヨード-2'-デオキシウリジン 上流と下流の製品情報
原材料
(4S)-2,6-ジオキソヘキサヒドロピリミジン-4-カルボン酸
Nucleoside
シトシン
2-プロピン-1-オール
オキサゾリン
2-アミノオキサゾール
5-ヨードウラシル
水酸化ナトリウム
酢酸
無水酢酸
5-chloromercurio-2-'-deoxyuridine
3a,6a-ジフェニル-1,3,4,6-テトラクロロ-3a,4,6,6a-テトラヒドロイミダゾ[4,5-d]イミダゾール-2,5(1H,3H)-ジオン
2'-デオキシ-3'-O,5'-O-ジアセチルウリジン
チミン
5-(TriMethylstannyl)-2'-deoxyuridine
4-チオ-2'-デオキシウリジン
3'-O,5'-O-ジアセチル-5-ヨード-2'-デオキシウリジン
2'-デオキシウリジン
準備製品