Suppression of Herpes Simplex Virus Infection by Phosphonoacetic Acid

The synthesis of monoesters (P and C) of phosphonoacetic acid (PA) is given. The carboxyl esters were prepared by two methods: the reaction of chloroacetates with tris(trimethylsilyl) phosphite, followed by hydrolysis; and by the acid-catalyzed esterification of PA with the appropriate alcohol. P-Monoesters of PA were prepared either by the reaction of alkyl[bis(trimethylsilyl)] phosphite with benzyl chloroacetate followed by deprotection or by the reaction of dimethylphenyl phosphite with benzyl bromoacetate followed by hydrogenolysis. Three aryl- (alkyl-)phosphinic acid derivatives are reported. The above compounds were evaluated for anti-herpes activity against HSV-induced DNA polymerase and in animals infected with herpes dermatitis.

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confidence: 99%

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confidence: 99%

Synthesis and anti-herpes simplex activity of analogs of phosphonoacetic acid

Tr¹,

Js²,

Rr³

et al. 1977

“…Although the medication was discontinued after 4 days, no relapse of infection was observed in the group of animals by day 7 when only a few scabs remained. Scab formation in the placebo-treated animals was observed only after 7 days.…”

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confidence: 94%

Antiviral activity of some .beta.-diketones. 3. Aryl bis(.beta.-diketones). Antiherpetic activity

Diana¹,

Carabateas²,

Salvador³

et al. 1978

A series of bis(beta-diketones) was synthesized and tested in vitro for antiviral actitity against herpes simplex type 2. Two parameters which were studied in an effort to optimize activity were the nature of the aryl group and the length of the alkyl bridge. One of the more active compounds, 4,4'-[(1,4-phenylenedioxy)bis(6,1-hexanediyl)]-bis[3,5-heptanedione] (6), was evaluated more extensively and found to inhibit the cytopathic effect in tissue culture of herpes simplex virus type 1 as well as type 2. Compound 6 was evaluated in vivo topically against herpes simplex type 1 in experimentally induced skin infections in guinea pigs. A topical treatment with 2% of 6 in a vanishing cream base, administered 24 h postinfection applied five times daily for 4 days, significantly reduced the number and size of herpetic vesicles.

“…1975, 234, 195. (5) Spitzer, R. L., chairperson "Diagnostic and Statistical Manual of Mental Disorders"; American Psychiatric Association: a Results in this table were calculated by subtracting the percent correct scores of control group from those of the drug group. 6 Drugs administered ip 1 h prior to retention testing. c Not testable, mice too excited.…”

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confidence: 99%

“…(5) The cyclic lactam must be the pyrrolidin-2-one, as the corresponding piperidin-2-one with a usually effective side chain (41) is markedly less active. (6) The acetamide spacing is critical, since the corresponding propionamide (42), with a good side chain, is almost inactive. (7) The presence of the inverted U-shaped doseeffect curve can be seen repeatedly in the results in Table II.…”

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confidence: 99%

Amnesia-reversal activity of a series of N-[(disubstituted-amino)alkyl]-2-oxo-1-pyrrolidineacetamides, including pramiracetam

Butler¹,

Nordin²,

L'Italien³

et al. 1984

A series of N-[(dialkylamino)alkyl]-2-oxo-1- pyrrolidineacetamides was synthesized. The title compounds reversed electroconvulsive shock (ECS) induced amnesia in mice when administered subsequent to the ECS treatment and were inactive in a general observational test for central nervous system (CNS) activity. Active compounds exhibited an inverted U-shaped dose-response curve. Among the compounds with the broadest dose-response curve, as well as the most potent, were those with the N-[2-[bis(1-methylethyl)amino] ethyl] or 2,6- dimethylpiperidinoethyl residues as amide substituent. The N-(dialkylamino) substituent markedly enhances amnesia-reversal activity, with ethylene providing the optimal chain length. N-[2-[Bis(1-methylethyl)amino]ethyl] -2-oxo-1- pyrrolidineacetamide N-(dialkylamino) substituent was selected for preclinical toxicological evaluation, assigned the investigational number CI-879 and the U.S. adopted name ( USAN ) pramiracetam . Pramiracetam demonstrated a wide margin of safety in animals and was well tolerated in normal human volunteers. It has shown encouraging activity in an open label trial in patients with primary degenerative dementia (PDD or senile dementia of the Alzheimer's type).