Comparative theoretical studies of energetic pyrazole-pyridine derivatives

The pyrazole-pyridine derivatives were optimized to obtain their molecular geometries and electronic structures at the DFT-B3LYP/6-31G(d,p) and DFT-B3P86/6-31G(d,p) levels. Molecular mechanics (MM) calculations were performed for the title compounds. Heats of formation (HOFs) were predicted through designed isodesmic reactions. Detonation performance was evaluated by using the Kamlet-Jacobs equations based on the calculated densities and heats of formation. The thermal stability of the title compounds was investigated via the bond dissociation energies (BDEs). The simulation results reveal that the compound with one pyrazole ring that is fully nitro-substituted performs similarly to the famous explosive HMX, and the compound with two pyrazole rings that are fully nitro-substituted outperforms HMX. According to the quantitative standard of energetics and stability as high energy density materials (HEDMs), the compound with two pyrazole rings that are fully nitro-substituted essentially satisfies this requirement.     

Clinical pharmacology studies with Centchroman.

A pharmacological evaluation of centchroman (3,4-trans-2,2,dimethyl-3-phenyl-4-p-(beta-pyrrolidino ethoxy)-phenyl-7-methoxychroman), a new postcoital contraceptive, in normal healthy human volunteers was performed to determine the maximum tolerated dose and to discover any abnormal toxic effects in humans. The study was carried out for both men and women as a double-blind noncrossover trial in 2 parts: 1) a single dose study (40 volunteers) and 2) a multiple dose study (28 females) for 30 days. Centchroman was well tolerated without significant side effects in single doses up to 320 mg, severalfold higher than the anticipated therapeutic dose. In the multiple dose schedule, the compound was found safe at doses of 60-120 mg/day. however, similar effects were observed in subjects receiving placebo and are not unexpected in a normal population over a 1-month period. Centchroman is presently undergoing clinical trials for postcoital contraceptive efficacy in humans.     

Antioxidative activities of novel diphenylalkyl piperazine derivatives with high affinities for the dopamine transporter

A new series of diphenylalkyl piperazine derivatives with high affinities for the dopamine transporter (DAT), which were modified at both the diphenylalkyl moiety and the phenyl ring in the phenylamino moiety of 1-[4,4-bis(4-fluorophenyl)butyl]-4-[2-hydroxy-3-(phenylamino)propyl]piperazine 1, was evaluated for their inhibitory activities against auto-oxidative lipid peroxidation in canine brain homogenates. Some of these were approximately equivalent in activity to alpha-tocopherol as a potent antioxidant with IC(50) values of low micromolar order, and the 4-hydroxyphenyl derivative 11 showed the most potent antioxidative activity with an IC(50) value of 0.32 microM, exhibiting approximately 5-fold more potent activity than alpha-tocopherol. The structure-activity relationship (SAR) studies of the antioxidative activity of these derivatives are presented.     

Chemotaxonomic studies onArachniodes (dryopteridaceae) I. Phloroglucinol derivatives of japanese species

Twelve species ofArachniodes from Japan were examined for phloroglucinol derivatives and glandularity of rhizome and petiole bases. For comparison 3 species ofDryopteris, 1 species ofCtenitis, 4 species ofPolystichum, and 1 species ofAcystopteris were also investigated. Phloroglucinol derivatives were detected for the first time by sensitive TLC in the followingArachniodes, Dryopteris andPolystichum species:A. amabilis, A. dimorphophylla, A. exilis, A. hasseltii, A. maximowiczii, A. miqueliana, A. mutica, A. nipponica, A. okinawensis, A. simplicior incl. var.major, D. hayatae, D. sparsa, andP. tsus-simense. On the other hand,A. pseudo-aristata, A. standishii, P. polyblepharum, P. pseudomakinoi, P. retroso-paleaceum, Ctenitis maximowicziana, andAcystopteris japonica were totally lacking phloroglucinols. The phloroglucinol containing species ofArachniodes andPolystichum contained external glands, whereas those ofDryopteris contained internal and/or external glands. External glands are common inDryopteris sect. Nephrocystis. In taxa lacking phloroglucinols no glands were present. The homologous iso-aspidins BB and AB were detected in ferns for the first time.     

Comparative studies of mucopolysaccharides from marine animals. I. Raja eglanteria Bosc.

A mucopolysaccharide (MPS) was extracted from the pectoral fins of the skate, Raja eglanteria Bosc. The purified MPS had an anticoagulant activity of 28 IU/mg and an optical rotation value, [α]_D²⁵, of ?9°. The MPS was analyzed for uronic acid, hexosamine, N-sulfate, O-sulfate, O-sulfate, and neutral sugar. This analysis suggests that this MPS is an over-sulfated chondroitin sulfate, the electrophoretic pattern and infra-red spectrum of which are similar to chondroitin sulfate.