pyrimidinones and Edema

Addressing the global need for the development of safe and potent NSAIDs, new series of oxadiazolo and thiadiazolo fused pyrmidinones were synthesized and initially tested for their analgesic activity. All tested compounds showed promising analgesic activity compared with the reference standard indomethacin. Moreover, anti-inflammatory activity evaluation, ulcerogenic liability, and in vitro COX-1, COX-2 enzyme inhibition assays were also performed for the most active derivatives. The methoxyphenyl piperazinyl derivative 3d showed analgesic activity surpassing indomethacin with protection of 100%, and 83%; respectively. Also 3d showed good anti-inflammatory activity with relatively lower ulcer index compared with other tested compounds, and potent COX-1 and COX-2 inhibitory activity with IC

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Behavior, Animal; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Disease Models, Animal; Drug Design; Edema; Humans; Male; Mice; Pyrimidinones; Quantitative Structure-Activity Relationship; Rats; Rats, Wistar

New pyrazolo[3,4-d]pyrimidinone and pyrazolo[4,3-e][1,2,4]triazolo[4,3-a]pyrimidinone derivatives were synthesized. They have been evaluated for their anti-inflammatory activity using in vitro (COX-1/COX-2) inhibitory assay. Moreover, compounds with promising in vitro activity and COX-1/COX-2 selectivity indices were subjected for in vivo anti-inflammatory testing using formalin induced paw edema and cotton-pellet induced granuloma assays for acute and chronic models, respectively. Compounds (2c, 3i, 6a, 8 and 12) showed promising COX-2 inhibitory activity and high selectivity compared to celecoxib. Most of the compounds exhibited potential anti-inflammatory activity for both in vivo acute and chronic models. Almost all compounds displayed safe gastrointestinal profile and low ulcerogenic potential guided by histopathological examination. Furthermore, molecular docking experiments rationalized the observed in vitro anti-inflammatory activity of selected candidates. In silico predictions of the pharmacokinetic and drug-likeness properties recommended accepted profiles of the majority of compounds. In conclusion, this work provides an extension of the chemical space of pyrazolopyrimidinone and pyrazolotriazolopyrimidinone chemotypes for the anti-inflammatory activity.

Topics: Animals; Anti-Inflammatory Agents; Binding Sites; Celecoxib; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Diclofenac; Edema; Female; Granuloma; Inflammation; Molecular Docking Simulation; Molecular Structure; Pyrazoles; Pyrimidinones; Rats, Wistar; Structure-Activity Relationship; Triazoles

Fifty two compounds based on 5-nitropyrimidine-2,4-dione moiety have been synthesized and evaluated for their inhibitory potency on the production of nitric oxide. Among them, compound 36 inhibited the production of nitric oxide (IC50 : 8.6 μm) on lipopolysaccharide-induced RAW 264.7 cells and inducible nitric oxide synthase activity (IC50 : 6.2 μm), as well as exerted no potential cytotoxicity (IC50 > 80.0 μm). Docking study confirmed that compound 36 was an inducible nitric oxide synthase inhibitor with perfect binding to the active site of inducible nitric oxide synthase. At a dose of 10 mg/kg, oral administration of 36 possessed protective properties in carrageenan-induced paw edema of male ICR mice.

Topics: Administration, Oral; Animals; Binding Sites; Carrageenan; Catalytic Domain; Cell Line; Drug Evaluation, Preclinical; Edema; Enzyme Inhibitors; Hydrogen Bonding; Lipopolysaccharides; Macrophages; Male; Mice; Mice, Inbred ICR; Molecular Docking Simulation; Nitric Oxide; Nitric Oxide Synthase Type II; Pyrimidinones; Styrenes; Uracil

A new series of thienopyrimidinones is synthesized and evaluated as selective phosphodiesterase 7 (PDE7) inhibitors for the treatment of inflammatory diseases. The modification of the substituents on thienopyrimidinone revealed that an isopropylamino group at the 2-position was favorable for aqueous solubility. The introduction of 3-pyrrolidines at the 7-position resulted in good solubility, highly potent activity, and good PDE7 selectivity. Among the synthesized compounds, compound 46 exhibited the greatest inhibition of ear edema in a phorbol ester-induced mouse model.

Topics: Animals; Cyclic Nucleotide Phosphodiesterases, Type 7; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Male; Mice; Mice, Inbred ICR; Models, Molecular; Molecular Structure; Phorbol Esters; Pyrimidinones; Solubility; Structure-Activity Relationship; Substrate Specificity

The 3D QSAR studies based on generation of common pharmacophore hypotheses (CPHs) were performed separately for the series of 1,2,3,4-tetrahydropyrimidin-5-yl-acetic acid and 2-(4-sulfonylphenyl)pyrimidine analogs for their in-vivo anti-inflammatory activity and in-vitro COX-2 inhibitory activity respectively. The main idea of selecting two different series was to develop two 3D QSAR models for same scaffold (1,2,3,4-tetrahydropyrimidine/pyrimidine) for same target, but with different aspects of activity. The aim of study was to screen designed compounds and select new compounds with increased COX-2 selectivity. The best 3D QSAR model from both group was employed as 3D search query to screen the designed 4,5,6-triphenyl-1,2,3,4-tetrahydropyrimidine derivatives. The new compounds showing good predicted activity were selected for experimental studies. Among the synthesized compounds, 5c and 5f showed highest anti-inflammatory activity.

Topics: Animals; Cyclooxygenase 2 Inhibitors; Disease Models, Animal; Drug Design; Edema; Female; Male; Models, Chemical; Models, Molecular; Molecular Structure; Pyrimidines; Pyrimidinones; Quantitative Structure-Activity Relationship; Rats; Sulfones; Thiones

Novel series of 2-methyl-3-{3-methyl-5-[(E)-2-phenyl-1-ethenyl]-4-isoxazolyl}-3,4-dihydropyrimido[4,5-b]quinolin-4-ones 5 and 3-{3-methyl-5-[(E)-2-phenyl-1-ethenyl]-4-isoxazolyl}-3,4-dihydro-2H-chromeno[2,3-d]pyrimidin-4-ones 7 have been synthesized from isoxazolyl cyanoacetamide synthon 2. Compound 2 was obtained by reaction of 4-amino-3-methyl-5-styrylisoxazole 1 with ethyl cyanoacetate. Isoxazolyl pyrimido[4,5-b]quinolin-4-ones 5 were obtained from compounds 2 by condensation with o-nitro benzaldehyde followed by treatment with SnCl(2) and subsequent tandem N-acetylation and cyclodehydration with acetic anhydride. Compounds 2 were converted to isoxazolyl chromeno[2,3-d]pyrimidin-4-ones 7 by reaction with salicylaldehydes and subsequent cyclization with formaldehyde. Compounds 2-7 were characterized by IR, (1)H NMR, (13)C NMR, and Mass spectral data. The title compounds 5a-f and 7a-g were evaluated for their antimicrobial, anti-inflammatory and analgesic activity. Compounds 5d and 7e exhibited significant antimicrobial activity, potent anti-inflammatory and analgesic activities as that of standard drugs.

Topics: Analgesics; Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Bacteria; Behavior, Animal; Chemistry Techniques, Synthetic; Drug Design; Edema; Fungi; Isoxazoles; Microbial Sensitivity Tests; Pyrimidinones; Quinolines; Rats

Novel 3-substituted-1-aryl-5-phenyl-6-anilino-pyrazolo[3,4-d]pyrimidin-4-ones of pharmacological significance were synthesized by the reaction of ethyl-(5-amino-3-methylthio-1-aryl-5-phenyl-2H-pyrazole)-4-carboxylates 3a-c with S-methyl diphenyl thiourea independently to produce 1-aryl-3-thiomethyl-5-phenyl-pyrazolo[3,4-d]pyrimidines 4a-c in DMF with catalytic amount of K(2)CO(3), which on further treatment with different aromatic amines independently under same reaction conditions generated for compounds 5a-l. The compounds were screened for the anti-inflammatory activity and evaluated for ulcerogenic potential. The compounds 5i exhibited superior anti-inflammatory activity in comparison with diclofenac sodium and comparable activity with celecoxib at a dose of 25mg/kg. The other compounds 4c, 5c, 5f and 5l were found as active with inhibition of edema in the range of 35-39 after 3 h of administration of test compounds. The ulcerogenic potential of active compounds was observed to be quite lesser as compared to standard. COX-2 docking score of the active compound 5i was found to be better than standard celecoxib.

Topics: Animals; Anti-Inflammatory Agents; Celecoxib; Diclofenac; Dose-Response Relationship, Drug; Edema; Molecular Structure; Protein Binding; Pyrazoles; Pyrimidinones; Rats; Sulfonamides

A large number of patients are switched to second-line antiretroviral therapy, especially in resource limited settings. Lopinavir/Ritonavir is the main drug used in second-line treatment regimens. We describe a patient attending an HIV treatment centre in Kampala, Uganda, who presented with bilateral non-tender pitting inflammatory edema two weeks after switching to a Lopinavir/Ritonavir-containing second-line treatment regimen. The lack of an alternate explanation led us to suspect that Lopinavir/Ritonavir was potentially responsible for the edema.

Topics: Anti-HIV Agents; Edema; HIV Infections; Humans; Leg; Lopinavir; Male; Middle Aged; Pyrimidinones; Ritonavir; Uganda

An immunopharmacological profile of 2, 7-dimethyl-3-nitro-4H pyrido [1,2-a] pyrimidine-4-one (P-I) has been investigated using in vitro and in vivo models representing various features of Type I allergy. P-I prevented compound 48/80-mediated histamine release from rat peritoneal mast cells. A promising anti-inflammatory activity of P-I was evident in active paw anaphylaxis (mice) and carragenan-induced paw edema (rat). P-I inhibited eosonophil accumulation and eosinophil peroxidase activity in bronchoalveolar lavage fluid from ovalbumin challenged balb/c mice: in these animals blood levels of IL-5, and CD4+ T cells also remained attenuated. A promising bronchorelaxant effect of P-I was observed in histamine-contracted guinea pig tracheal chain via its antagonism to H1 receptor. These findings were compared with some known compounds (ketotifen, cetirizine and promethazine). The anti-histaminic, anti-inflammatory and bronchorelaxant activities of P-I has been discussed in context with its potential profile as an anti-allergic and anti-asthmatic agent.

Topics: Animals; Anti-Inflammatory Agents; Bronchodilator Agents; Cytokines; Edema; Eosinophils; Histamine H1 Antagonists; Male; Mice; Mice, Inbred BALB C; Pyridines; Pyrimidinones; Rats; Rats, Wistar; Trachea

Pain and inflammation are simultaneous responses in bacterial infections. In current clinical practice, two groups of agents like antibacterial and non-steroidal anti-inflammatory drugs (NSAID's) are prescribed simultaneously. Regrettably, none of the drug possesses these activities in a single component. Exploiting the bioisosterism concept, we have documented that 2-phenyl-3-substituted quinazolines, 2,3-disubstituted quinazolines, 2-methyl-3-substituted quinazolin-4-(3H)-ones and 2-methylthio-3-substituted quinazolin-4-(3H)-ones exhibited good analgesic and anti-inflammatory activities. The present work is an extension of our ongoing efforts towards the development and identification of lead molecules by bioisostere concept, for which we designed some of 2-methylthio-3-substituted-5,6-dimethylthieno[2,3-d] pyrimidin-4(3H)-ones. The title compounds were investigated for analgesic, anti-inflammatory and antibacterial activities. While the test compounds exhibited significant activity, the compounds (6-9) showed more potent analgesic activity, and the compounds (8, 9) showed anti-inflammatory activity comparable to the reference standard diclofenac.

Topics: Analgesics, Non-Narcotic; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Bacteria; Carrageenan; Drug Design; Edema; Indicators and Reagents; Magnetic Resonance Spectroscopy; Microbial Sensitivity Tests; Pain Measurement; Pyrimidinones; Rats; Reaction Time; Structure-Activity Relationship; Thiophenes; Thiourea

In the present work, design, synthesis, and pharmacological evaluation of the analgesic, anti-inflammatory, and ulcerogenic-index activities of new 3-subsituted-amino-2-methylsulfanyl-5,6,7,8-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-ones, structurally planed by exploiting a clear concept of bio-isosterism, are reported. All compounds exhibited significant analgesic and anti-inflammatory activity. Compounds A1, A3 showed higher analgesic activity and more potent anti-inflammatory activity than that of the reference compound diclofenac sodium. Interestingly, the test compounds showed only mild ulcerogenic potential when compared to that of acetylsalicylic acid.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Edema; Female; Magnetic Resonance Spectroscopy; Male; Pain Measurement; Pyrimidinones; Rats; Rats, Wistar; Stomach Ulcer; Structure-Activity Relationship; Sulfones; Thiophenes

We established a new and facile model to investigate allergic mechanism and assess the effect of antiallergic compounds. Male Wistar rats were actively or passively sensitized. Active sensitization was performed by injection of both dinitrophenylated-ovalbumin (DNP-OA) and Bordetella pertussis. Nine days later, DNP-OA was injected into the right hind footpad. This antigen challenge induced a biphasic footpad swelling that consisted of an early-phase (EPR) and a late-phase response (LPR). In rats passively sensitized with rat anti-DNP-OA serum, DNP-OA induced only EPR. The EPR was suppressed by disodium cromoglycate, a mast cell stabilizer, but not by cyclosporin A, an immunosuppressant, while the LPR was suppressed by cyclosporin A. Furthermore, to investigate these two allergic responses determined by the interactions between the hapten and the carrier proteins, two distinct haptenated antigens were created. DNP-Ascaris (DNP-As) induced a marked EPR and LPR in DNP-As-sensitized rats. However, DNP-As induced only EPR in DNP-OA-sensitized rats, indicating that the usage of the same carrier protein in both sensitization and challenge was necessary for induction of LPR. These data suggest that this actively sensitization model in which EPR and LPR are functionally distinguishable should be useful for evaluating the efficacy of antiallergic compounds.

Topics: Aminopyridines; Animals; Anti-Allergic Agents; Antigens; Cromolyn Sodium; Cyclosporine; Dinitrobenzenes; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Evaluation, Preclinical; Edema; Haptens; Hindlimb; Hypersensitivity, Delayed; Male; ortho-Aminobenzoates; Ovalbumin; Passive Cutaneous Anaphylaxis; Promethazine; Pyridines; Pyrimidinones; Quinolones; Rats; Rats, Wistar

A variety of novel 2-methylthio-3-substituted-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-4(3H)-ones have been synthesized by reacting (2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-3-yl)dithiocarbamic acid methyl ester (5) with a variety of amines. The starting material dithiocarbamate (5) was synthesized from 2-amino-3-carbethoxy-4,5,6,7-tetrahydrobenzo (b) thiophene (1) by a novel innovative route. The title compounds were investigated for analgesic, anti-inflammatory, ulcerogenicity index and antibacterial activities. While the test compounds exhibited significant activity, the compounds 1-methyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-3-yl)thiourea (A1), 1-dimethyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-3-yl)thiourea (A2), 1-diethyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-3-yl)thiourea (A3) and 1-pyrrolidinyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-3-yl)thiourea (A4) showed more potent analgesic activity and the compounds 1-dimethyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d]pyrimidin-3-yl)thiourea (A2), 1-diethyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno-[2,3-d]pyrimidin-3-yl)thiourea (A3) and 1-pyrrolidinyl-3-(2-methylthio-4-oxo-3H-5,6,7,8-tetrahydrobenzo (b) thieno[2,3-d] pyrimidin-3-yl)thiourea (A4) showed more potent anti-inflammatory activity than the reference standard diclofenac sodium.

Topics: Analgesics; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Edema; Female; Magnetic Resonance Spectroscopy; Male; Mass Spectrometry; Mice; Microbial Sensitivity Tests; Pyrimidinones; Rats; Rats, Wistar; Spectroscopy, Fourier Transform Infrared; Stomach Ulcer

The synthesis, the analgesic and anti-inflammatory activities of two series of phenyl derivatives containing 5,6-dimethyl-thieno[2,3-d]pyrimidin-4(1H)-one and 4H-pyrimido[5,4-b]indol-4-one system, respectively, are reported. Two of these derivatives, 6A and 9B, showed interesting activities. The results of the pharmacological assays are discussed.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Edema; Guinea Pigs; Indicators and Reagents; Indoles; Male; Pain Measurement; Peritonitis; Pyrimidines; Pyrimidinones; Rats; Rats, Sprague-Dawley; Spectrophotometry, Infrared; Spectroscopy, Fourier Transform Infrared; Stomach Ulcer

Topics: Adult; Antiretroviral Therapy, Highly Active; Edema; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Lopinavir; Male; Middle Aged; Pyrimidinones

Topics: Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Edema; Female; HIV Infections; HIV Protease Inhibitors; Humans; Inflammation; Leg; Lopinavir; Male; Middle Aged; Pyrimidinones

Because interferon-gamma, interleukin-4, and interleukin-5 have been identified at the mRNA and protein levels in the lesional skin of patients with atopic dermatitis, we investigated the roles played by granulocytes as effector cells in allergic inflammation by using two unique murine skin models. In vitro generated Th1 and Th2 cells from naïve splenocytes of antiovalbumin T cell receptor transgenic BALB/C mice were adoptively transferred with ovalbumin into the ear pinnae or air-pouches produced in the back skin of naïve, nontransgenic BALB/C mice. The injection of Th1 cells with ovalbumin induced delayed type ear swelling that peaked at 48 h, whereas that of Th2 resulted in ear swelling that peaked at a much earlier time, 24 h. Histologic study of the swollen ear skin and granulocytes recruited into the air-pouch demonstrated that, although the Th1-induced inflammation caused a neutrophil-predominant infiltrate with few eosinophils, larger numbers of eosinophils accumulated in the Th2-induced inflammation. Using these murine models, we further evaluated the effects of drugs used for the treatment of atopic diseases. The results showed that FK506 administration could effectively reduce skin inflammation induced by either Th cells. Interestingly, the neutrophil elastase inhibitor ONO-6818 efficiently inhibited Th1-induced inflammation. In contrast, a leukotriene receptor antagonist, ONO-1078, specifically suppressed Th2-induced inflammation. We also found that each ONO drug exerted direct influence on specified granulocytes, as neither affected in vitro production of relevant Th cytokines. Thus, we succeeded in developing animal skin inflammation models in which we can evaluate the contribution of protein antigen-specific Th1 or Th2 cells through the action of granulocytic effector cells.

Topics: Animals; Cells, Cultured; Chromones; Dermatitis, Atopic; Disease Models, Animal; Ear; Edema; Enzyme Inhibitors; Eosinophils; Hypersensitivity; Immunosuppressive Agents; Leukotriene Antagonists; Male; Mice; Mice, Inbred BALB C; Neutrophils; Ovalbumin; Oxadiazoles; Pyrimidinones; Skin; Tacrolimus; Th1 Cells; Th2 Cells

New thiadiazolothienopyrimidinones were synthesized in continuation of efforts to prepare thienopyrimidine derivatives with analgesic and antiinflammatory activities. In this study, the effect of various substituents in the thiophene ring on the pharmacological activity of the compounds was investigated.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Chemical Phenomena; Chemistry, Physical; Edema; Lethal Dose 50; Magnetic Resonance Spectroscopy; Male; Mice; Pain Measurement; Peritonitis; Pyrimidinones; Rats; Spectrophotometry, Infrared; Stomach Ulcer; Thiazoles

Topics: Acetates; Acetic Acid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzoquinones; Carrageenan; Edema; Magnetic Resonance Spectroscopy; Pain Measurement; Peritonitis; Pyrimidines; Pyrimidinones; Rats; Spectrophotometry, Infrared; Thiadiazines; Thiophenes

Anti-carrageenin paw edema effects of 1-(m-trifluoromethylphenyl)-3-(2-hydroxyethyl)-quinazoline-2, 4(1H, 3H)-dione [H-88] and 1-(m-trifluoromethylphenyl)-3-ethylpyridopyrimidine-2, 4(1H, 3H)-dione [HN-37] in rats were dissipated or reduced markedly by adrenalectomy. The effects of both compounds on the pituitary-adrenal axis were therefore investigated in male Wistar rats at 5-6 weeks of age. Oral treatments with H-88 in a dose of 100 mg/kg and HN-37 at 10 mg/kg induced the same degree of responses in intact animals, namely, a marked increase of blood corticosterone level at one hr of the peak time (360%), a decrease of adrenal ascorbic acid level at 3 hr (52-59%), an increase of blood glucose level at 6-12 hr (25-59%) and of liver glycogen level at 12-4 hr (97-153%). In addition, a significant hypertrophy of the pituitary and adrenals (p less than 0.05) at 6-12 hr and/or atrophy of the thymus and spleen at 3-24 hr were noted. The effect of HN-37 on blood corticosterone level was approximately 10 times as potent as that of H-88 as well as on the carrageenin paw edema. The effects of both compounds on blood corticosterone level were dissipated by adrenalectomy, and those on blood corticosterone level and adrenal ascorbic acid level were abolished by hypophysectomy. These results suggest that hypophysis-adrenal axis stimulation may play an important role in antiedematous effects of N-88 and HN-37.

Topics: Adrenal Glands; Adrenalectomy; Animals; Ascorbic Acid; Circadian Rhythm; Corticosterone; Dose-Response Relationship, Drug; Edema; Hypophysectomy; Male; Organ Size; Pituitary-Adrenal System; Pyrimidinones; Quinazolines; Rats

1,6-Dimethyl-4-oxo-1,6,7,8,9,9a-hexahydro-4H-pyrido[1,2-a]pyrimidine-3-carbamide (Chinoin 127), a non-narcotic analgesic with potent antiinflammatory activity is described. Chinoin-127 is more potent as an analgesic in the hot plate, Randall-Selitto and writhing tests than is acetylsalicylic acid (ASA) and an effective antiphlogistic agent in a battery of tests (carrageenin, kaolin and dextran induced rat paw edema, Northover test, carrageenin induced abscess, implanted cotton pellet method, adjuvant arthritis) used for measuring antiinflammatory activity. The PG-synthesis inhibitors (indometacin, suprofen) were found to be devoid of analgesic activity, and great test-dependent variations in their antiinflammatory effect were observed. They proved to be inactive in the Northover test. Unusual grade of inhibition in the carrageenin-induced rat paw edema test was obtainable by the simultaneous administration of Chinoin 127 and indometacin.

Topics: Abscess; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Capillary Permeability; Carrageenan; Dextrans; Edema; Female; Granuloma; Kaolin; Male; Mice; Prostaglandins; Pyrimidinones; Rats; Stomach Ulcer

The unequivocal synthesis of some terms belonging to the two isomeric classes of the pyrrolo(1H,3H)[3,4-d]pyrimidin-2-ones and of the pyrrolo(1H,6H)[3,4-d]pyrimidin-2-ones is reported. Some of these compounds are active in inhibiting the development of the carrageenin edema, of the granuloma cotton pellet and of the adjuvant arthritis in the rat when administered orally.

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Aspirin; Edema; Female; Indomethacin; Male; Mice; Pyrimidinones; Pyrroles; Rats

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Carrageenan; Edema; Freund's Adjuvant; Pyridines; Pyrimidinones; Rats; Structure-Activity Relationship

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Edema; Lethal Dose 50; Mice; Pyrimidinones; Thiophenes