Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.1 (chymotrypsin)
 10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A series of derivatives of 4-arylthiazole acetic acid and 2-aminothiazole were studied with respect of their antiinflammatory effect in rat carrageenin edema. Some active compounds were found, which suppressed the paw edema formation strongly, and two compounds were selected, 4-(4-chlorophenyl)-2-phenylaminothiazole acetic acid (Compd. 29) and 4-(4-chlorophenyl)-2-diethylaminothiazole acetic acid (Compd. 71) for further detailed studies. These compounds (Compd. 29 and Compd. 71) moderately inhibited the denaturation of albumin with heat-treatment. Hyperthermic lysis of erythrocytes were strongly inhibited with both Compds. 29 and 71 in the wide range of concentrations (5 X 10(-5) mol/l-5 X 10(-4) mol/l), while their related compound, Compd. 2 (fentiazac) and the reference drugs, ibuprofen, phenylbutazone and flufenamic acid, were either ineffective or stimulatory at the higher concentration. Compds. 29 and 71 inhibited strongly both trypsin and chymotrypsin activities, which differed from the above reference drugs qualitatively and quantitatively. The adverse effect on the gastrointestinal membrane was less with Compd. 29 and Compd. 71 compared with fentiazac and ibuprofen. Compd. 29 especially gave the preferable results with almost no gastric damage at the higher dosage together with its good anti-edematous activity. The characteristics of Compds. 29 and 71 are discussed in terms of the correlation between anti-inflammatory effect and ulcerogenic effect and also of the clinical application.
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PMID:Studies on the anti-inflammatory activity and ulcerogenic adverse effect of thiazole derivatives, especially 2-amino-thiazoleacetic acid derivatives. 654 May 78

A series of 3-(phenylsulfonyl)-1-phenylimidazolidine-2,4-dione derivatives have been synthesized and evaluated for their ability to selectively inhibit human heart chymase. The structure-activity relationship studies on these compounds gave the following results. The 1-phenyl moiety participates in a hydrophobic interaction where an optimum size is required. At this position, 3,4-dimethylphenyl is the best moiety for inhibiting chymase and showed high selectivity compared with chymotrypsin and cathepsin G. A 3-phenylsulfonyl moiety substituted with hydrogen-bond acceptors such as nitrile and methoxycarbonyl enhances its activity. Molecular-modeling studies on the interaction of 3-[(4-chlorophenyl)sulfonyl]-1-(4-chlorophenyl)-imidazolidine-2,4-dione (29) with the active site of human heart chymase suggested that the 1-phenyl moiety interacts with the hydrophobic P1 pocket, the 3-phenylsulfonyl moiety resides in the S1'-S2' subsites, and the 4-carbonyl of the imidazolidine ring and sulfonyl group interact with the oxyanion hole and the His-45 side chain of chymase, respectively. The complex model is consistent with the structure-activity relationships.
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PMID:Substituted 3-(phenylsulfonyl)-1-phenylimidazolidine-2,4-dione derivatives as novel nonpeptide inhibitors of human heart chymase. 921 34

The effects of cannabinoid receptor agonists on the non-adrenergic non-cholinergic (NANC) inhibitory responses to electrical field stimulation in guinea-pig trachea were assessed. R-(+)-[2,3-dihydro-5-methyl-3-[(morpholilinyl) methyl]pyrrolo [1,2,3-de]-1,4-benzoxazin-6-yl]-(1-naphthalenyl)methanone mesylate (WIN 55,212-2; 10(-5) M) significantly enhanced the frequency-dependent response to electrical stimulation. The same concentration of R-(N)-(2-hydroxy-1-methylethyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (R(+)methanandamide) and 1-propyl-2-methyl-3-(1-naphthoyl)indole (JWH-015) did not affect significantly the electrically induced inhibitory NANC responses. The effect of WIN 55,212-2 was not modified by the cannabinoid CB1 and CB2 receptor-selective antagonists, N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride (SR141716A; 10(-5) M) and N-(1S)-endo-1,3,3-trimethyl bicyclo [2.2.1] heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR 144528; 10(-5) M), respectively. Moreover, the nitric oxide synthase inhibitor, L-NG-nitro-arginine methyl ester (L-NAME; 10(-4) M), but not the peptidase, alpha-chymotrypsin (2 U/ml), blocked the effect of WIN 55,212-2. Postsynaptically, WIN 55,212-2 did not produce any change of tracheal smooth muscle tone, either basal or histamine-induced, and did not interfere with the relaxant activity of the nitric oxide donor, sodium nitroprusside (10(-8)-10(-4) M). In conclusion, our results suggest that (a) cannabinoid CB1 and CB2 receptor stimulation does not alter the inhibitory NANC transmission in guinea-pig trachea, and (b) WIN 55,212-2 potentiates the NO-mediated component of the NANC relaxant response to electrical stimulation through a cannabinoid receptor-independent mechanism.
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PMID:Effects of cannabinoids on non-adrenergic non-cholinergic-mediated relaxation in guinea-pig trachea. 1295 67