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Biomedical subjects

H Tagawa

Publications and source records attributed to H Tagawa.

At least 127 records · Page 7Linked to original sources
PubMed1982

Synthesis and antitumor activity of 10-alkyl-10-deazaminopterins. A convenient synthesis of 10-deazaminopterin.

Requirements for large-scale synthesis of the potent antitumor drug 10-deazaminopterin have led to development of a facile synthesis of this compound and its 10-alkyl analogues. The lithium diisopropyl amide generated dianions of appropriate p-alkylbenzoic acids were alkylated with 3-methoxyallyl chloride. The resulting 4-(p-carboxyphenyl)-1-methoxy-1-butenes were brominated at pH 7-8 to afford the 2-bromo-4-(p-carboxyphenyl)butyraldehydes. Condensation with 2,4,5,6-tetraminopyrimidine and subsequent in situ oxidation of the resulting dihydropteridines yielded crystalline 10-alkyl-10-deaza-4-amino-4-deoxypteroic acids. The pteroic acids were coupled with diethyl glutamate via the mixed anhydride method, followed by saponification at room temperature, to give the target 10-deazaminopterins. The 10-alkyl compounds were approximately equipotent to 10-deazaminopterin as growth inhibitors of folate-dependent bacteria. Their abilities to inhibit Lactobacillus casei and L1210 derived dihydrofolate reductases were also similar. Transport properties in vitro were suggestive of an improved therapeutic index for the 10-alkyl analogues. Against L1210 in mice, the percent increase in life span at the LD10 dosage was +151% (methotrexate), +178% (10-deazaminopterin), +235% (10-methyl analogue), and +211% (10-ethyl analogue). 10,10-Dimethyl-10-deazaminopterin was less effective at an equimolar dosage, but the ILS at the maximum dose tested (72 mg/kg) was +135%. It was far less toxic than the other analogues possibly because of enhanced clearance.

Aminopterin↗
PubMed1980

A new socket design for the dysplastic acetabulum in total hip replacement.

A special socket was designed by holography for total hip replacement for the treatment of the dysplastic acetabulum and correction of the deformation pattern. Excellent clinical results of 12 cases demonstrate that the special socket design provides good stability as well as favorable redistribution of mechanical forces about the hip joint.

Acetabulum↗
PubMed1980

[Painful hip joint with epiphyseal dysplasia (author's transl)].

Among patients who visited our hip clinic, eighteen patients from ten families were diagnosed as mild or atypical cases of spondyloepiphyseal dysplasia or multiple epiphyseal dysplasia. Clinical and X-ray examinations of these patients showed common characteristic features as follows. 1. They usually had short stature but were not dwarfs. Their facial features and body proportions did not suggest hereditary bone dysplasia. 2. Although the disease might be transmitted in an autosomal dominant manner, its occurrence among these families was found to be sporadic. 3. Symptoms of the hip joint mainly resulted from limited range of motion, coxalgia being usually less than expected from X-ray findings. 4. Joints were always affected bilaterally although the degree might be different on each side. 5. In the majority of the cases, the spine, shoulder (in 7 cases), knee (in 6 cases), elbow (in 3 cases), ankle, and wrist joint (in 2 cases) were also affected. 6. Characteristic X-ray findings of the hip joints were as follows. a) Coxa vara, flattening or rectanglar deformity of the femoral head and shortening of the femoral neck. b) The trabecular pattern of the femoral head was irregular and subchondral cysts were often observed. c) Joint space was relatively better restored than expected from the deformity and subchondral bony changes of the femoral head. Spondyloepiphyseal dysplasia and multiple epiphyseal dysplasia are genetic disorders of the epiphyseal and apophyseal cartilage. The hip joint is loading greater mechanical force than any other joint. In both spondyloepiphyseal dysplasia and multiple epiphyseal dysplasia, the hip joint is always affected. As the hip joint is most vulnerable when there is some disorder of the epiphyseal cartilage, it is probably the only detectable abnormal joint. In relatively short period (1972-1978), the diagnosis of mild or atypical spondyloepiphyseal dysplasia was made in 18 patients in our hip clinic. This means that the mild or atypical cases of spondyloepiphyseal dysplasia is not so rare as expected. They might be misdiagnosed as aseptic necrosis, deformity of the femoral head due to Perthes disease or primary osteoarthrosis. An extreme care should be taken when we examine such patients.

Adult↗
PubMed1978

Nonsteroidal antiinflammatory agents. 2. Derivatives/analogues of dibenz[b,e]oxepin-3-acetic acid.

6,11-Dhydro-11-oxodibenz[b,e]oxepins and some related compounds have been synthesized and evaluated for antiinflammatory effect according to the carrageenan paw edema method in rats. The structure-activity relationships have been discussed among acetic acid, carboxylic acid, alcohol, and tetrazole derivatives of dibenzoxepins and acetic acid derivatives of thienobenzoxepins and of the corresponding thiepins. The 3-isopropyl alcohol 9 and 11-deoxo-3-propionic acid (49) were more active than indomethacin but not as active as the title compound (i.e., 43). Carboxylic acids, tetrazoles, esters, amides, and ketones were less active than the corresponding acetic acids. Three compounds (31, 33, and 34) were evaluated for ulcerogenicity and lethality but none surpassed 6,11-dihydro-11-oxodibenz[b,e]oxepin-3-acetic acid (41) in therapeutic ratio.

Animals↗
PubMed1976

6,11-Dihydro-11-oxodibenz [b,e] oxepinacetic acids with potent antiinflammatory activity.

A series of 6,11-dihydro-11-oxodibenz[b,e]oxepinacetic acids was synthesized and the antiinflammatory activity determined. Studies on 29 compounds revealed certain structure-activity relationships. In the carrageenan edema test, eight compounds exhibited higher antiinflammatory activities than did indomethacin. Several compounds (2, 9, 14, 22, 25) also proved to have activities superior or comparable to indomethacin in suppressing chronic as well as acute inflammation and carrageenan-induced hyperesthesia. Gastric irritation and lethality rates were less frequently observed with these compounds.

Acetates↗