Bristol-myers Company

The Kendall Company

Colgate Palmolive Company

Westwood Pharmaceuticals, Inc.

Julius A Vida

Carlos M Samour

Theodore S Wang

Kenneth A Kerridge

Various derivatives of barbituric acid and of diphenylhydantoin are described in which alkoxymethyl or benzyloxymethyl groups are attached to the nitrogen atoms of the rings. Therapeutic compositions containing these compounds and their use as anti-convulsant agents are described.

Alkoxymethyl and benzyloxymethyl phenobarbital therapeutic compositions

Alkoxymethyl and benzyloxymethyl phenobarbital compounds

.beta.-Methoxyethoxymethyl esters of cephalosporins and penicillins are exemplified by such esters of hetacillin and heta-amoxicillin were synthesized and found to exhibit advantageous biological properties.

Methoxyethoxymethyl esters of penicillins

It is disclosed that compounds of the formula: ##STR1## wherein Y represents (C.dbd.O).sub.m in which m has a value of 0 or 1; n has a value of 0 or 1; and X represents S, NH or O; provided that there is a COOH substituent at the 1, 2 or 3 position relative to the X group; and further provided that when X is NH and n is O, the COOH group cannot be at the 2 position; or a nontoxic, pharmaceutically acceptable salt thereof are capable of decreasing the ratio of the rates of bone resportion to bone deposition in a host animal, e.g., in the treatment of osteoporosis.

Antiosteoporotic agents

It is disclosed that compounds of the formula: ##STR1## WHEREIN Y represents (C.dbd.O).sub.m in which m has a value of 0 or 1; n has a value of 0 or 1; and X represents S, NH or O; provided that there is a COOH substituent at the 1, 2 or 3 position relative to the X group; and further provided that when X is NH and n is 0, the COOH group cannot be at the 2 position; or a nontoxic, pharmaceutically acceptable salt thereof are capable of decreasing the ratio of the rates of bone resorption to bone deposition in a host animal, e.g., in the treatment of osteoporosis.

It is disclosed that compounds of the formula: ##STR1## WHEREIN Y represents (C.dbd.O).sub.m in which m has a value of 0 or 1; n has a value of 0 or 1; and X represents S, NH or O; provided that there is a COOH substituent at the 1, 2 or 3 position relative to the X group; and further provided that when X is NH and n is O, the COOH group cannot be at the 2 position; and further provided that when n is 0, the carboxyl group is attached to the ring containing the X and Y ring members or a nontoxic, pharmaceutically acceptable salt thereof are capable of decreasing the ratio of the rates of bone resportion to bone deposition in a host animal, e.g., in the treatment of osteoporosis.

N-mono(alkoxymethyl)phenobarbitals wherein the alkoxy group has 1 to 4 carbon atoms are disclosed. The compounds are prepared by reacting the dialkali metal salt of thiophenobarbital with chloromethyl alkyl ether followed by treating the resultant N,S-bis(alkoxymethyl)thiophenobarbital with an oxidizing agent. The compounds are useful as anti-convulsant agents.

Therapeutic composition containing an N-mono (alkoxy-methyl)

N-mono (alkoxymethyl)phenobarbitals wherein the alkoxy group has 1 to 4 carbon atoms are disclosed. The compounds are prepared by reacting the dialkali metal salt of thiophenobarbital with chloromethyl alkyl ether followed by treating the resultant N,S-bis(alkoxymethyl)thiophenobarbital with an oxidizing agent. The compounds are useful as anticonvulsant agents.

Process for preparing N-mono(alkoxymethyl) phenobarbitals

Various derivatives of barbituric acid and of diphenylhydantoin are described in which alkoxymethyl or benzyloxymethyl groups are attached to the nitrogen atoms of the rings. Therapeutic compositions containing these compounds and their use as anticonvulsant agents are described.

Certain barbituric acid derivatives used as anticonvulsant agents

There is disclosed an improved process for the preparation of 1,3-bis(alkoxyalkyl)- and 1,3-bis(benzyloxyalkyl)-5,5-disubstituted barbituric acid derivatives, such as 1,3-bis(methoxymethyl)phenobarbital, by reacting e.g., phenobarbital, preferably, a multiple molar excess of dimethoxymethane and an at least equimolar amount of anhydrous stannic chloride based on the amount of phenobarbital.

Method of making barbituric acid derivatives

It is disclosed that 2-(4'-pyridyl)-1,3-dioxolane methiodide and 2-(1'-methyl-4'-piperidyl)-1,3-dioxolane hydroiodide are neuromuscular blocking agents or neuromuscular blocking agent antagonists, depending upon the amount of the drug administered. At doses of 10.sup.-.sup.6 to 10.sup.-.sup.4 gm./kg. of body weight, they antagonize or reverse the effects of neuromuscular blocking agents, such as d-tubocurarine and succinylcholine, produce post-drug repetitive activity (PDR), block post-tetanic potentiation (PTP), have no direct muscle effect and reverse the PTP suppression caused by d-tubocurarine and succinylcholine; and at doses of 10.sup.-.sup.3 to 10.sup.-.sup.2 gm./kg. of body weight they act as neuromuscular blocking agents.

Neuromuscular blocking agents and antagonists

N-mono(alkoxymethyl)phenobarbitals wherein the alkoxy group has 1 to 4 carbon atoms are disclosed. The compounds are prepared by reacting the dialkali metal salt of thiophenobarbital with chloromethyl alkyl ether followed by treating the resultant N,S-bis(alkoxymethyl)thiophenobarbital with an oxidizing agent. The compounds are useful as anticonvulsant agents.

N-mono(alkoxymethyl) phenobarbitals, process therefor and therapeutic

1,3-Bis(halomethyl)phenobarbitals are prepared by reacting phenobarbital with formaldehyde and a chlorine source or a bromine source at a temperature of -10.degree. to 200.degree.C in the presence of a Lewis acid catalyst, the formaldehyde and bromine or chlorine source being employed in at least approximately twice the molar amounts of phenobarbital. These compounds are useful anticonvulsant agents.

Process for preparing 1,3-bis(halomethyl)phenobarbitals

5-Pivaloyloxy-5-(1-phenylethyl) barbituric acid, a method of treating symptoms of pain in warm-blooded animals employing said compound and a therapeutic composition containing same are disclosed.

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Greenwich, CT, United States of America

Julius A Vida