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A series of 2-alkoxyimino- N -(2-isoxazolin-3-ylmethyl)acetamides and related compounds were synthesized and their antiviral activities against human influenza A virus were assessed. Studies of the structure–activity relationships revealed the strongest antiviral activity when position-5 of the isoxazoline ring was substituted with a tert -butyl group. When the alkoxyimino moiety was substituted with a methyl, ethyl, isopropyl or allyl group, good antiviral activity was obtained. Among the geometrical isomers at the oxime moiety, the E -isomers were more active than the Z -isomers. Among the compounds examined, ( E )-2-allyloxyimino-2-cyano- N -(5- tert -butyl-2-isoxazolin-3-ylmethyl)acetamide ( 1j ) was the most active inhibitor with an EC 50 of 3 μg/mL in vitro.

A series of the title compounds was prepared via condensation of the 3-(aminomethyl)triazolylbenzophenone (5) with N-protected amino acids, followed by deprotection, amination of the 3-[(chloroacetamido)methyl]triazolylbenzophenone (6a,b), or reduction of the relevant azide derivative (6c). Some of the title compounds were also derived directly from the quinazolines 3 or 4 by acid-induced rearrangement, followed by deprotection. These new amino acid amide derivatives of the triazolylbenzophenones (2) were evaluated for central nervous system (CNS) activity. Members of this class of compounds exhibited a high level of CNS activities. For example, 2',5-dichloro-2-[3-[(glycylamino)methyl]-5-methyl-4H-1,2,4-triazol-4-yl] benzophenone (2c) was as active as triazolam, with an ED50 of 0.58 mg/kg (mice, po), against antifighting activity in the foot shock-induced fighting test. Other triazolylbenzophenone derivatives (2a-f) showed similar pharmacological activities.

A novel method of synthesizing 2-disubstituted-amino-4-arylthiazol-5-ylalkanoic acids (3) was studied. Dehydration of S-(α-benzoyl-β-ethoxycarbonyl) ethyl 1-piperidinethiocarbonate (5a) in the presence of aqueous perchloric acid-acetic anhydride yielded 4-ethoxycarbonyl-methyl-5-phenyl-2-piperidino-1, 3-oxathiolium perchlorate (1a). Nucleophilic reaction of ammonia with 1a afforded 5-ethoxycarbonylmethyl-4-phenyl-2-piperidinothiazole (2a). Acid-catalyzed hydrolysis of 2a gave 3a as a hydrochloride. The acids (3) were also synthesized by the classical Hantzsch method. These alkanoic acids were evaluated as antiinflammatory agents on carrageenin-induced abscess in rat.

The action of two equivalents of NaOEt on thiamin hydrochloride in EtOH gives a neutral compound. Spectroscopic data and its chemical behavior indicated that the compound is thiamin ylide 1. The chemical behaviors of 1 are entirely consistent with those of in situ generated thiamin ylide.

The reaction of 2-dialkylamino-5-phenyl-1,3-oxathiolium cation 1 with sulphur ylides 2 was investigated. The behavior of 1 was solvent-dependent. In CH 2 Cl 2 , carbamate ester 3 was obtained: in CH 3 CN, the intermediate sulphonium salt 5 , which on hydrolysis gave 3 , was isolated. On the other hand, reaction in MeOH gave the diphenacyl derivative 6 . The reaction mechanism is discussed.

Peptidoaminobenzophenones (1), terminal N-substituted peptidoaminobenzophenones (14), and acylglycylaminobenzophenones (16) were prepared as a novel series of ring-opened derivatives of 1,4-benzodiazepine. Z-Gly- and Z-Ala-N-methylaminobenzophenones (4) were treated with HBr-HOAc to give Gly- and Ala-N-methylaminobenzophenone hydrobromides (8). Reaction of 8 with chloroacetyl chloride in dimethylformamide (DMF) or hexamethylphosphoramide (HMPA) gave chloracetamide (13), which was allowed to react with various amines to afford a number of terminal N-substituted derivatives (14). Reaction of 8 with various acyl halides in HMPA or DMF gave a number of acylglycyl-N-methylaminobenzophenones (16). Peptidoaminobenzophenones (1) were also prepared by several convenient methods. Many of these compounds exhibited high CNS activity in animals when given orally. In antianxiety activity the potency of some compounds is equal to or higher than that of diazepam.

The influence of the contribution of the dipolar form to the resonance hybrid structure on the chemical stability of 1, 3-dithiol- and oxathiol-2-ylidene derivatives was investigated by means of infrared, ultraviolet, nuclear magnetic resonance, and dipole moment measurement. It is concluded that though the contribution of the polar form to the resonance hybrid is small, it is nevertheless important for double bond isomerization through nonbenzenoid aromatic stabilization of its positive charge. Protonation of the double bond in acid medium does not necessarily occur, since some of the title compounds are not Hammett bases.

A series of noval peptidoaminobenzophenones has been prepared via several routes and was evaluated for CNS activity. The structure--activity relationships in the series are discussed. In general, dipeptido-N-methylaminobenzophenones showed higher activities than the corresponding NH derivatives. Some compounds had very high activities in antipentylenetetrazole and antifighting tests in mice when orally administered. Very weak toxicity was also found in these compounds. Water solubility of the peptidoaminobenzophenones and their salts were tested. Possible in these compounds. Water solubility of the peptidoaminobenzophenones and their salts were tested. Possible in vivo conversion of peptidoaminobenzophenone by enzymatic cleavage of the terminal amino acid, followed by chemical cyclization to 1,4-benzodiazepine, is also discussed. Such novel open-ring derivatives of 1,4-benzodiazepine may serve as useful CNS agents.