1. An outline of the chemical structure of bacterial cell wall peptidoglycans was described to make it easy to understand the chemical basis of immunopharmacological activities of cell walls and related synthetic compounds (muramyl peptides). 2. Immunopharmacological activities of cell walls and muramyl peptides which have been detected by in vivo and in vitro assays were tabulated with comprehensive literatures. 3. Recent data obtained in our and cooperative laboratories on the immunopharmacological activities of cell walls and related compounds were presented in some detail. 4. A new aspect in which cell wall peptidoglycans and muramyl peptides are regarded as an endogenous immunomodulator or a vitamin was discussed.

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Hydration of cinepazide maleate (DD-3357), a vasodilate agent, has been examined by means of solubility test and moisture equilibrium test. Consequently, it was clarified that DD-3357 was converted into a stable dihydrate (DD-3357·2H₂O) in water and/or under higher humidity conditions, and that the driving force for the conversion was ascribed to the enthalpy change, ΔH_{A, H}=-5.5 kcal/mol for the hydration reaction. On the other hand, the dehydration reaction of DD-3357·2H₂O was investigated by means of thermal analysis. Kinetic analysis of the TG curve indicated that the dehydration reaction followed the first-order rate reaction with an activation energy of 29.0 kcal/mol. The heat of dehydration reaction was also discussed using the results from DSC.

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Phthalazine 2-oxide (I) reacted with dimethyl acetylenedicarboxylate (IIa) to afford 2-phthalazinium 3-methoxy-1-methoxycarbonyl-2, 3-dioxopropylide (III), methyl pyrrolo [2, 1-α] phthalazine-1, 2, 3-tricarboxylate (IVa), methyl 2-hydroxy-1, 3-naphthalenedicarboxylate (V), methyl 1, 2-epoxy-2, 3-naphthalenedicarboxylate (VIa) and VII (C₁₇H₁₅NO₇). Compound I reacted with methyl propiolate (IIb) to afford methyl pyrrolo [2, 1-α]-phthalazine-1, 3-dicarboxylate (IVb), methyl 3-hydroxy and 4-hydroxy-2-naphthalenecarboxylate (IXa, IXb), and methyl 3, 4-epoxy-2-naphthalenecarboxylate (VIb). The structures of XIII, XIV and XVII, which were obtained in the reaction of 1-phenylphthalazine 3-oxide (XII) with II, were presumed to be methyl 1-phenyl-2-methoxycarbonyl-α-oxo-indene-2-ethanoate (XIII), methyl 1-phenyl-2-benzoxepine-3, 4-dicarboxylate (XIV), and methyl 3-hydroxy-4-phenyl-2-naphthalenecarboxylate (XVII), respectively. It is considered that these products are formed by the liberation of nitrogen from 1, 3-dipolar cycloadducts.

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From the aerial parts of Tetragonia tetragonoides, compound A and B₁ (tentative names) were isolated as principles which prevented ulcer formation in mice under restrained and water immersion conditions. Compound A was confirmed to be a mixture of steryl-β-D-glucosides. The sterol moiety of compound A consisted of β-sitosterol, α-spinasterol, schottenol, Δ²²-stigmastenol, stigmasterol, stigmastanol, and campesterol.

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The reaction of 3-benzyloxy-4-methyl-2-nitrobenzoyl chloride (I) with alkylenediamines in THF-H₂O gave N, N'-bis (3-benzyloxy-4-methyl-2-nitrobenzoyl) alkylenediamines (IIa-f), which were converted to the corresponding aminobenzoyldiamines (IIIa-f) by catalytic reduction. These products (IIIa-f) were treated with air or potassium ferricyanide to afford N, N'-(2-amino-4, 6-dimethyl-3-oxo-3H-phenoxazine-1, 9-dioyl) alkylenediamines (IVa-f) by intramolecular cyclization.

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The main metabolite of benoxaprofen (BXP), an acidic anti-inflammatory analgesic, was isolated from human urine and identified as a glucuronide of BXP (BXP-G). BXP-G could be also detected in human blood though the amount was very slight. An improvement was attempted to the hydrolysis process in the assay method for BXP-G described by Chatfield, et al. BXP-G in urine or plasma could be rapidly and completely hydrolyzed to BXP in potassium hydroxide without any additional degradation. Thus, the present method was more accurate and less time-consuming for the assay of BXP-G than the Chatfield's method.

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The stability and degradation of sodium 7β-[(2R, 3S)-2-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-3-hydroxybutanamido]-7α-methoxy-3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylate (T-1982) in aqueous solution were investigated. The solutions of T-1982 of various pH (μ=0.5) were kept at 35°C, and its degradation was followed by HPLC. T-1982 was stable in the range of pH 3.0-6.0, slightly unstable at lower pH and markedly unstable at higher pH than this range. It was confirmed that in alkaline solution, 7β-[(2R, 3S)-2-[3-[2-(N-ethyl-N-oxaloamino) ethyl] ureido]-3-hydroxybutanamido]-7α-methoxy-3-[(1-methyl-1H-tetrazol-5-yl)-thiomethyl]-3-cephem-4-carboxylic acid (T-1982A), 7α-methoxy-7β-[(5-methyl-2-oxooxazolidin-4-yl) carboxamido-] 3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylic acid (T-1982B) and 1-ethyl-2, 3-dioxopiperazine (T-1982C) were produced, and that in acidic solution, 5-mercapto-1-methyl-1H-tetrazole (T-1982F), (2R, 3S)-2-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-N-(1-formyl-1-methoxy) methyl-3-hydroxybutanamide (T-1982H) and methyl [(2R, 3S)-2-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-3-hydroxybutanamido] acetate (T-1982J) were produced.

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In order to investigate the relationship between the chemical structures and the antibacterial activities, three α-decanoylpentapeptides, containing a D-Phe, Leu or Arg were synthesized by the acylation of pentapeptide obtained by the condensation of tripeptide and dipeptide with dicyclohexylcarbodiimide. It was proved that the α-decanoylpentapeptide containing Arg has the strongest antibacterial activities against gramnegative bacteria in synthesized α-decanoylpentapeptides.

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Four kinds of α-acyl-Lys-cyclo (-Lys-Thr-Lys-D-Leu-) were synthesized to investigate the relationship between the chemical structure and the antibacterial activities by acylation of the corresponding cyclic pentapeptides. Acyl chlorides of (+)-6-methyloctanoic acid (a component of colistin) and three kinds of other organic acid were employed as acylating agents. It was proved that the α-(±)-3, 7-dimethyloctanoyl-Lyscyclo (-Lys-Thr-Lys-D-Leu-) in them shows the strongest antibacterial activities, and that these compounds have stronger antibacterial activities against gram-negative bacteria than the corresponding liner acylpentapeptides.

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Kinetic analysis of thermal decomposition was carried out using thermogravimetry (TG) and differential scanning calorimetry (DSC). The linear equations of n order, phase-boundary, nucleation growth and diffusion-controlled reaction under linear heating conditions were derived for the estimation of the rate constant and the activation energy. The method to determine the reaction mechanism was shown by evaluation of linearity. The equations were applied to the TG and DSC curves of dehydration of calcium oxalate monohydrate and elimination of carbon monoxide from calcium oxalate. The dehydration was fit to two-dimensional phase-boundary reaction and the activation energy was calculated as 85 kJ/mol. But the dehydration at a high-speed heating rate proceeded as apparent three-dimensional diffusion-controlled reaction. The elimination of carbon monoxide from calcium oxalate was fit to phase-boundary reaction and the activation energy was calculated as 196 kJ/mol for three-dimensional phase-boundary reaction and 182 kJ/mol for two-dimensional phase-boundary reaction.

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Effects of six kinds of additives in injections, i. e. benzyl alcohol, HCO-60, macrogol 4000, urethan, sodium bisulfite and sodium sulfite, on the blood were investigated, and the following results were obtained ; 1) In the concentrations of additives contained in injections benzyl alcohol inhibited the platelet aggregation and the inorganic salts had the inhibitory effects on both the blood coagulational and fibrinolytic phenomena. The action of sodium bisulfite on the blood was recognized to be based on pH and that of sodium sulfite to be ascribed to SO₃^2-. 2) The injections which contain both benzyl alcohol and sodium bisulfite as additives are commercially available. However, they are not evaluated to be desirable injections from the standpoints of hematology, especially of coagulation, fibrinolysis and platelet aggregation.

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Adduct formation was confirmed between dimethylamine and six sulfonamides (sulfadiazine, sulfisomidine, sulfamethoxypyridazine, sulfamethoxazole, sulfathiazole, and sulfisoxazole). The thermal, micromeritical and other physico-chemical properties of these adducts as well as their desorbed products were investigated by differential scanning calorimetry, thermogravimetry, thermomicroscopy, infrared spectroscopy, X-ray powder diffractometry, electron microscopy, and BET gas adsorption analysis. The composition of the sulfathiazole adduct was not clarified by any method ; however, the combining ratios of other adducts were found to be 1 : 1 except that sulfisomidine formed 1 : 2 adduct. As new absorption bands arising from NH₂⁺ stretching vibration appeared in the infrared spectra of all the adducts, it was considered that ionic bonding force would principally participate in the adduct formation. Although desorption of dimethylamine from these adducts was rather difficult, the adducts of sulfadiazine, sulfisomidine, sulfamethoxypyridazine, and sulfamethoxazole released combined dimethylamine without liquefaction by heating under reduced pressure. The original sulfonamides thus recovered were effectively micronized and their specific surface areas were about twice larger those via the corresponding ammonia adducts. It was concluded that these findings would be explainable by the basic strength and the molecular volume of dimethylamine.

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When the plasma concentration-time curves of furosemide after bolus intravenous injection in the rat were analyzed, it seemed that three-exponential equation fitted in the lower dose, and two-exponential equation in the higher dose. However, the relationship between doses and areas under the plasma concentration-time curve (AUC) was nonlinear over the dose range from 10 mg/kg to 30 mg/kg. From the one-compartment model analysis with constant-rate intravenous infusion of drug, parameters for Michaelis-Menten elimination kinetics in hepato-portal compartment were estimated by using the graphical technique. The pharmacokinetics of furosemide could be expressed by the proposed nonlinear model with two saturable processes at the elimination in hopato-portal compartment and the urinary excretion.

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The degrees of pain induced by the injection of sodium cephalothin (CET), and its degradation products, deacetylcephalothin (DeCET) and deacetoxycephalothin (DeOCET), were examined by means of writhing response of mice. It was found that these drugs caused slightly painful symptoms, and thought to be likely that the acetic acid liberated during storage was responsible for the pain. CET, dissolved in 0.1 M phosphate buffer at pH 6.2 and 7.0, and stored at 4°C, showed no acid formation and no pain increase, but when stored at 37°C, the solution, in spite of its buffer action, showed remarkable pH decrease, and caused the pain to increase. This was also found in the cases with sodium cephacetrile (CEC) and sodium cephapirin (CEP). In descending order of pH and in ascending order of inducing pain were CEP, CET, and CEC.

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