Novel peptidoaminobenzophenones, terminal N-substituted peptidoaminobenzophenones, and N-(acylglycyl)aminobenzophenones as open-ring derivatives of benzodiazepines

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.     

Neuropathological studies of the spinal cord in early stage HTLV-I-associated myelopathy (HAM).

Necropsy findings for a patient with HTLV-I-associated myelopathy (HAM) of 9 months clinical duration are reported. Loss of myelin sheaths and axons together with perivascular lymphocytic infiltration was seen in the lateral and posterior columns of the spinal cord from the cervical to the lumbar region where vacuolar changes caused by the splitting of myelin sheaths were prominent. Immunohistochemical analyses revealed CD8+ cytotoxic T cell infiltration predominated in the absence of HTLV-I core protein antigen bearing-cells in the brain and spinal cord. Myelin sheath damage and predominant CD8+ cytotoxic T cell infiltration are thought to be the main neuropathological findings in the spinal cord in early stage HAM.