Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A series of 1-benzoyl- and 1-phenylisoquinolineacetic acid derivatives was prepared and tested for antiinflammatory activity. The most potent compound synthesized, 1-(4-chlorophenyl)-3-isoquinolineacetamide, was as active as phenylbutazone in the Evans blue carrageenan-induced pleural effusion assay but inactive in the adjuvant-induced arthritis model of chronic inflammation.
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PMID:Aroyl- and arylisoquinolineacetic acids as antiinflammatory agents. 67 56

The synthesis of a series of substituted heterocyclic alkoxypropionic acids is described. They were evaluated for antiinflammatory effects in two animal models of chronic inflammation; adjuvant arthritis and type II collagen arthritis in the rat. The desired profile of biological activity was characterized by the reduction of inflammation with the coincident restoration toward normal levels of the biochemical markers (acute phase proteins) associated with the inflammatory response, an effect that was not shared by classical nonsteroidal antiinflammatory agents. Romazarit, (Ro 31-3948, 7), 2-[[2-(4-chlorophenyl)-4-methyl-5-oxazolyl]methoxy]-2-methylpropio nic acid, was selected for further evaluation. In contrast to NSAIDs, romazarit was inactive in animal models of acute inflammation, and furthermore it did not inhibit the cyclooxygenase enzyme in vitro or in vivo. Inhibition of interleukin-1-mediated events in vitro has been observed.
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PMID:Romazarit: a potential disease-modifying antirheumatic drug. 199

The biologic effects of a new potential disease-modifying antirheumatic drug, romazarit (Ro 31-3948, 2-[[2-(4-chlorophenyl)-4-methyl-5-oxazolyl]methoxy]-2-methylpropio nic acid), have been investigated. In a 5-day adjuvant arthritis model, romazarit inhibited the development of hindpaw inflammation with a minimum effective dose of 30 mg kg-1. Plasma levels of the acute phase reactants seromucoid and haptoglobulin were also significantly reduced. Romazarit was equally effective in adrenalectomized animals, indicating that the compound is not acting via stimulation of the pituitary/adrenal axis. When the developing adjuvant arthritis was extended to 15 days romazarit showed dose-related improvements of all the symptoms of arthritis with a minimum effective dose of 25 mg kg-1. Romazarit caused a dose-dependent (range 20-250 mg kg-1) reduction in both the inflammatory and bony changes occurring during collagen arthritis in the rat, without any significant effect on anticollagen antibody titers except at the highest dose. Collagenase and prostaglandin E2 production in cultures of talus bones taken from rats with collagen arthritis were reduced by romazarit. In vitro romazarit was an extremely weak inhibitor of prostaglandin synthetase activity in both sheep seminal vesicle (IC50 6500 microM) and rat renal medulla (IC50 greater than 300 microM) cell-free preparations. Romazarit showed little or no activity in models of acute inflammation such as rabbit skin edema, carrageenan pleurisy or UV-induced erythema. In both acute and chronic tests romazarit displayed no ulcerogenic potential. In comparison with the structurally similar compound clobuzarit, hepatic changes such as increases in catalase and peroxisome proliferation-associated 80,000 mol.wt. protein were markedly less with romazarit. Clinical studies with romazarit are currently in progress.
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PMID:Biologic properties of romazarit (Ro 31-3948), a potential disease-modifying antirheumatic drug. 215 99

A number of D-penicillamine (PA) derivatives (3-benzoyl-4-mercaptobutyric acids) with an acetylthio group on the gamma-position of the carboxylic acid were synthesized. Their immunological effects were examined and compared with PA and other immunosuppressors. PA derivatives suppressed adjuvant-induced arthritis in SD and Lewis rats, suppressed delayed-type hypersensitivity and IgE antibody response in mice, and prolonged the survival time of NZBXNZW F1 hybrid (BWF1) mice, as did immunosuppressors. In vitro, PA derivatives suppressed lymphocyte transformation and the proliferation of KB cells. 4-Acetylthio-3-[-4-(4-chlorophenyl)benzoyl]butyric acid was the most effective of the PA derivatives. Thus, these PA derivatives with an acetylthio group on the gamma-position of the carboxylic acid showed immunosuppressive effects and, furthermore, substitution of the halogen atom on the phenyl group increased immunosuppressive activities.
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PMID:Immunopharmacological studies of new 3-benzoyl-4-mercaptobutyric acid derivatives. II. Immunosuppressive effects. 321 94

The carrageenan-induced paw oedema in the rat was chosen as the experimental model for acute antiphlogistic activity. ED50 values of 3 mg/kg p.o. for indometacin and of 17 mg/kg p.o. for [2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2, 3-dihydro-1H-pyrrolizine-5-yl]-acetic acid (ML 3000) at calculated plasma levels (micrograms/ml) of approximately 5.0 and 20.0 were recorded for indometacin and ML 3000, respectively. The activity ratio of indometacin: ML 3000 is therefore about 1:6 with regard to the oral dose and about 1:4 with regard to the calculated plasma level. Indometacin is more potent than ML 3000 on the one hand, but on the other hand ML 3000 is better tolerated by the stomach in this experimental study: the ulcerogenic dose UD50 (indometacin) is 7 mg/kg p.o., whereas ML 3000 is tolerated well up to the highest tested dose of 100 mg/kg p.o. The adjuvant arthritis in the rat served as the model for chronic antiphlogistic activity. ML 3000 at doses of 20 mg/kg/d p.o. and higher, and indometacin at a dosage of 2 mg/kg/d p.o. produced a similar rate of reduction of the adjuvant-induced secondary lesions and paw swelling of the injected and uninjected paws, following prophylactic as well as therapeutic treatment with the compounds.
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PMID:Acute and chronic anti-inflammatory properties of [2,2-dimethyl-6-(4- chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine-5-yl]-acetic acid. 789 65

We have evaluated the effect of a novel anti-rheumatic drug, cis-2-(4-chlorophenyl)-4,5-diphenyl-2-imidazoline hydrochloride (TA-383), on type II collagen (CII)-induced arthritis in DBA/1J mice. Treatment with TA-383 (0.4 mg/kg/day) from the day of immunization with CII strongly suppressed the arthritic responses. Increased serum interleukin 6 (IL-6) level was lowered in parallel with the effect. Effect of TA-383 on IL-6 production was examined in vitro. TA-383 inhibited the production of IL-6 by murine synovial fibroblasts stimulated with recombinant interleukin 1 (IL-1) beta in a dose-dependent manner (0.1-10 microM). Neither the general protein synthesis nor the expression of type I IL-1 receptor was affected by TA-383. The results show that TA-383 possesses an inhibitory activity on IL-6 generation and suggest that the effect may partly contribute to the anti-arthritic effect of TA-383.
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PMID:Effect of a novel anti-rheumatic drug, TA-383, on type II collagen-induced arthritis--suppressive effect of TA-383 on interleukin 6 production. 836 26

We have investigated the effect of a novel anti-rheumatic drug, cis-2-(4-chlorophenyl)-4,5-diphenyl-2-imidazoline hydrochloride (TA-383), on macrophages. TA-383 (> or = 10(-9) M) significantly stimulated rabbit alveolar macrophage (AM) migration, and its migration-stimulatory activity was more potent than those of L-fucose (5 x 10(-3) M), lobenzarit disodium, bucillamine (SA-96) and salazosulfapyridine. In addition, TA-383 enhanced the production and/or release of macrophage migration enhancement factor by rabbit spleen cells. In vivo, TA-383 (0.4 mg/kg, p.o.) has suppressive effects on picryl chloride-induced delayed type hypersensitivity and type II collagen-induced arthritis in mice. These results suggest that the anti-rheumatic activity of TA-383 may be exerted through the dispersion of macrophages from inflammatory sites.
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PMID:The novel anti-rheumatic drug TA-383 has a macrophage migration enhancing activity. 924 33

The antinociceptive and anti-edematogenic effects of peripheral benzodiazepine receptor (PBR) ligands, Ro5-4864 (7-chloro-5- (4-chlorophenyl)-1,3-dihydro-1-methyl-2-H-1,4-benzodiazepine-2) and PK11195 (1-(2-chlorophenyl)-N-methyl-N(1-methylpropyl)-3-isoquinoline carboxamide), were studied in an experimental model of carrageenan/LPS -induced arthritis in rats. These effects were compared with those of indomethacin and dexamethasone. Both pre and post-treatments with PK11195 were found to be anti-edematogenic and antinociceptive. The lower dose (0.01 mg/kg) exhibited the higher anti-edematogenic effect. On the other hand, the higher dose (0.5 mg/kg) produced antinociception, but with a decreased anti-edematogenic effect. Ro5-4864 produced a negligible antinociception and anti-edematogenic effect as pretreatment, but a pro-edematogenic effect when given as post-treatment. Dexamethasone and indomethacin presented parallel and dose-dependent antinociceptive and anti-edematogenic effects. In conclusion, PK11195 can effectively diminish arthritic nociception and edema elicited by LPS, but probably by mechanisms different from those of dexamethasone or indomethacin. RO5-4864 seemed to have opposite effect on this model.
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PMID:Comparison of two PBR ligands with classical antiinflammatory drugs in LPS-induced arthritis in rats. 1267 5

The purpose of this paper is to explore the contribution of isoforms of cyclooxygenase (COX) to chronic inflammation in DBA/1J mice with type II collagen-induced arthritis (CIA). To address this question pharmacologically, we tested the effects of selective inhibitors of COX-1 and COX-2 on paw edema and the formation of arachidonic acid metabolites in the inflamed paws immunized with type II collagen (CII). Oral administration of FR140423 (3-(difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methylsulfinyl)phenyl]pyrazole), a selective inhibitor of COX-2, showed a dose-dependent anti-inflammatory effect in mouse CIA with ED(50) value of 0.20mg/kg. Indomethacin, a non-selective inhibitor of COX, also inhibited paw edema in this arthritic model. In contrast, the selective COX-1 inhibitors, FR122047 (1-[(4,5-bis(4-methoxyphenyl)-2-thiazoyl)carbonyl]-4-methylpiperazine hydrochloride) and SC-560 (5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole), had no effect in mouse CIA model. The increase of prostaglandin (PG) E(2) and thromboxane (TX) B(2) in the mouse inflamed paws was associated with the development of paw edema induced by CII. FR140423 dose dependently inhibited the levels of PGE(2) and TXB(2) in the CIA mouse paws with ED(50) values of 0.20 and 0.12 mg/kg, respectively, similar to indomethacin. In contrast, FR122047 and SC-560 had no effect. These results suggest that COX-2, but not COX-1, contributes to the edema and the formation of PGE(2) and TXB(2) in mouse CIA model.
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PMID:Role of cyclooxygenase-2, but not cyclooxygenase-1, on type II collagen-induced arthritis in DBA/1J mice. 1296 93

5-(Phenylthiophene)-3-carboxylic acid (2a), a metabolite of esonarimod (1), which was developed as a new antirheumatic drug, was considered as a lead compound for new antirheumatic drugs. A new series of 2a derivatives were synthesized and their characteristic pharmacological effects, that is their antagonistic effect toward interleukin (IL)-1 in mice and the suppressive effect against adjuvant-induced arthritis (AIA) in rats, were evaluated and compared with those of 1. The structure-activity relationships indicated that [5-(4-bromophenyl)-thiophen-3-yl]acetic acid (5d), methyl [5-(4-chlorophenyl)-thiophen-3-yl]acetate (5h), and methyl [5-(4-bromophenyl)-thiophen-3-yl]acetate (5i) suppressed AIA more potently than 1 and all of the other synthesized compounds.
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PMID:Synthesis and structure-activity relationships of 5-phenylthiophenecarboxylic acid derivatives as antirheumatic agents. 1455 88


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