• 약학회지
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• 제45권6호
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• pp.565-569
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• 2001

Five novel cinmetacin amide derivatives as potential nonsteroidal antiinflammatory and analgesic compounds were prepared and their antiinflammatory-analgesic activity was compared with cinmetacin. Cinmetacin and hydroxysuccinimide were reacted with dicyclohexyl carbodiimide to give cinmetacin active ester (4), which was treated with amines to yield cinmetacin amides (5-9). Compounds (5) and (9) gave stronger analgesic activity than cinmetacin and compounds (5), (6), (9) showed comparable antiinflammatory activity to cinmetacin.

• 약학회지
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• 제45권1호
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• pp.1-6
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• 2001

Nine cinmetacin derivatives as potential nonsteroidal analgesic and antiinflammatory compounds were prepared and their analgesic-antiinflammatory activity was compared with cinmetacin. Salicylic acid and phenols were reacted with dicyclohexyl carbodiimide (DCC) to give phenol salicylates (1-4). Cinmetacin was treated with DCC and phenol derivatives to yield cinmetacin esters (5-13). Compounds (5, 7, 8, 10, 12, and 13) showed stronger analgesic activity than cinmetacin, but only compound (5) showed comparable antiinflammatory activity to cinmetacin.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1997년도 춘계학술대회
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• pp.106-106
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• 1997

Cinmetacin, one of the candidate of NSAID of arylacetate group was developed into a prodrug SJ-151 with butendiol group to minimize its gastrointestinal side effects. We studied its excretion and distribution after single oral administration in rats. Male rats were orally administered with 30, 60, 80 or 120mg/kg of SJ-151 and their urine and stool were collected at 0, 6, 12, 24 and 48 hour after administration. To evaluate its tissue distribution, 120mg/kg of SJ-151 was orally given and samples of blood, liver, kidney and brain were taken at 0.5, 1, 2, 4, 8, 24, and 48 hour of administration. As results, less than 0.1% of administered SJ-151 was detected in 48 hour collected urine as its metabolite cinmetacin. 33-50% of administered SJ-151 was observed in 48 hour collected stool as SJ-151. 3-7% of excreted SJ-151 was observed in 48 hour collected stool as cinmetacin. SJ-151 and cinmetacin were not detected in the brain regardless of dosage. SJ-151 was detected neither in kidney nor in liver. Only cinmetacin was observed in both organs with kidney concentrations higher than liver throughout the observation period. On the whole, organ concentration of cinmetacin fluctuated through 0.1-1.5 times that of plasma. As no reports on the metabolism of SJ-151 or cinmetacin in specific organs has been published yet, any detailed explanation of these results needs further study and the plasma concentration profile of rats showed remarkable interspecies difference with dogs.

• Archives of Pharmacal Research
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• 제12권1호
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• pp.52-57
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• 1989

The structure of cinmetacin was determined by single crystal X-ray diffraction analysis. The compound was recrystallized from a mixture of acetone and water in orthorhombic, space group $P2_12_12_1$, with Z=4, a=35.681(8), b=9.482(2), c:5.071(1) ${\AA}$, $D_x=1.352 g/cm^3$, and $D_m=1.35g/cm^3$. The structure was solved by direct method and refined by least-squares procedure to the final R value of 0.036 for 1441 observed reflections ($F{\geq}3{\sigma}(F)$). The carboxyl group of the molecule is nearly perpendicular to the indole ring. The dihedral angle between indole ring and phenyl group is $64.5^{\circ}$. The molecules are linked together via O(1)-H ----O(3) hydrogen bonds, and arranged along 2-fold screw axis in the crystal. The intermolecular contacts are the normal van der Waals' forces.

• 대한약학회:학술대회논문집
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• 대한약학회 2001년도 Proceedings of the Pharmaceutical Society of Korea
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• pp.187.1-187.1
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• 2001

• 대한약학회:학술대회논문집
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• 대한약학회 2001년도 Proceedings of International Convention of the Pharmaceutical Society of Korea
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• pp.247.1-247.1
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• 2001

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.220-220
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• 1996

The objectives of this study were to evaluate the pharmacokinetics of SJ-151 which is a new NSAID in male Beagle dogs following a single oral dosing. Seven beagle dogs (10-l2kg) were all administered a single oral gavage(10mg/kg) of SJ-151 tablet and serial blood samples of approximately 5$m\ell$ were then drawn from the cephalic vein of each animal at 0(predose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24hours postdosc. SJ-151 (Cinmetacinㆍbutendiol)and cimetacin were quantified in the plasma fraction by HPLC assay. The pharmacokinetic parameters calculated from the plasma concentrations of SJ-151 in dayl are Cmax(ng/$m\ell$)509$\pm$248, Tmax(hr) 1.50$\pm$0.45, AUC(ng.hr/$m\ell$) 1,750$\pm$762, tl/2$\alpha$ 0.98$\pm$0.30, t1/2$\beta$ 12.0$\pm$6.75. The pharmacokinetic parameters calculated from the plasma concentrations of Cinmetacin in day 1 are Cmax(ng/$m\ell$)258$\pm$74.1, Tmax(hr)2.42$\pm$ 0.92, AUC(ng.hr/$m\ell$) 1,820$\pm$318, t1/2$\alpha$ 1.74$\pm$0.49, t1/2$\beta$ 25.4$\pm$13.4.