Synthesis, Biological, Spectroscopic and Computational Investigations of Novel -Acylhydrazone Derivatives of Pyrrolo[3,4-]pyridazinone as Dual COX/LOX Inhibitors.

Secure and efficient treatment of diverse pain and inflammatory disorders is continually challenging. Although NSAIDs and other painkillers are well-known and commonly available, they are sometimes insufficient and can cause dangerous adverse effects. As yet reported, derivatives of pyrrolo[3,4-]pyridazinone are potent COX-2 inhibitors with a COX-2/COX-1 selectivity index better than meloxicam.

Design, Synthesis, Biological Evaluation, and Molecular Docking Study of 4,6-Dimethyl-5-aryl/alkyl-2-[2-hydroxy-3-(4-substituted-1-piperazinyl)propyl]pyrrolo[3,4-]pyrrole-1,3(2,5)-diones as Anti-Inflammatory Agents with Dual Inhibition of COX and LOX.

In the present study, we characterize the biological activity of a newly designed and synthesized series of 15 compounds 2-[2-hydroxy-3-(4-substituted-1-piperazinyl)propyl] derivatives of pyrrolo[3,4-]pyrrole -. The compounds were obtained with good yields of pyrrolo[3,4-]pyrrole scaffold - with secondary amines in CHOH. The chemical structures of the compounds were characterized by H-NMR, C-NMR, FT-IR, and MS.

Interactions of -Mannich Bases of Pyrrolo[3,4-]pyrrole with Artificial Models of Cell Membranes and Plasma Proteins, Evaluation of Anti-Inflammatory and Antioxidant Activity.

Despite the widespread and easy access to NSAIDs, effective and safe treatment of various inflammatory disorders is still a serious challenge because of the severe adverse effects distinctive to these drugs. The Mannich base derivatives of pyrrolo[3,4-]pyrrole are potent, preferential COX-2 inhibitors with a COX-2/COX-1 inhibitory ratio better than meloxicam. Therefore, we chose the six most promising molecules and subjected them to further in-depth research.

An Overview of the Biological Activity of Pyrrolo[3,4-]pyridine Derivatives.

Pyrrolo[3,4-]pyridine is one of the six structural isomers of the bicyclic ring system containing a pyrrole moiety fused to a pyridine nucleus. The broad spectrum of pharmacological properties of pyrrolo[3,4-]pyridine derivatives is the main reason for developing new compounds containing this scaffold. This review presents studies on the biological activity of pyrrolo[3,4-]pyridines that have been reported in the scientific literature.

Design and Synthesis of N-Substituted 3,4-Pyrroledicarboximides as Potential Anti-Inflammatory Agents.

In the present paper, we describe the biological activity of the newly designed and synthesized series N-substituted 3,4-pyrroledicarboximides -. The compounds - were obtained in good yields by one-pot, three-component condensation of pyrrolo[3,4-]pyrrole scaffold (-) with secondary amines and an excess of formaldehyde solution in CHOH. The structural properties of the compounds were characterized by H NMR, C NMR FT-IR, MS, and elemental analysis.

Design, synthesis, biological evaluation and in silico studies of novel pyrrolo[3,4-d]pyridazinone derivatives withpromising anti-inflammatory and antioxidant activity.

Novel Mannich base analogues of pyrrolo[3,4-d]pyridazinone 7a,b-13a,b are designed and synthesized as potential anti-inflammatory agents. The title compounds are obtained via convenient one-pot synthesis with good yields. Their structures and properties are described by spectroscopic techniques and elemental analyses.

COX-1/COX-2 inhibition activities and molecular docking study of newly designed and synthesized pyrrolo[3,4-c]pyrrole Mannich bases.

In the present paper we describe the biological activity of newly designed and synthesized series of pyrrolo[3,4-c]pyrrole Mannich bases (7a-n). The Mannich bases were obtained in good yields by one-pot, three-component condensation of pyrrolo[3,4-c]pyrrole scaffold (6a-c) with secondary amines and an excess of formaldehyde solution in CHOH. The chemical structures of the compounds were characterized by H NMR, C NMR, FT-IR, and elemental analysis.

Antinociceptive, anti-inflammatory and smooth muscle relaxant activities of the pyrrolo[3,4-d]pyridazinone derivatives: Possible mechanisms of action.

The aim of this study was to evaluate the analgesic as well as anti-inflammatory activities of the new pyrrolo[3,4-d]pyridazinone derivatives. Moreover, the present study attempted to assess some of the mechanisms involved in the pharmacological activity of these compounds. In the previous studies it was shown that these compounds were highly active in the phenylbenzoquinone-induced 'writhing syndrome' test and had much lower activity in the hot plate, which indicates that mainly peripheral mechanisms of analgesia are involved in their effects.

Derivatives of pyrrolo[3,4-d]pyridazinone, a new class of analgesic agents.

A series of N2-{2-[4-aryl(benzyl)-1-piperazinyl(piperidinyl)]ethyl}pyrrolo[3,4-d]pyridazinones 4 and related derivatives 5 were synthesized as potential analgesic agents. The structures of the new compounds were elucidated by micro, spectral and X-ray analysis. Analgesic activity of the compounds was investigated in the phenylbenzoquinone induced 'writhing' and 'hot plate' test in mice and at radioligand binding assay.

Mechanism of solvolysis of N-[2-(4-o-fluorophenylpiperazin-1-yl)ethyl]-2,5-dimethyl-1-phenylpyrrole-3,4-dicarboximide (PDI).

The stability of N-[2-(4-o-fluorophenylpiperazin-1-yl)ethyl]-2,5-dimethyl-1-phenylpyrrole-3,4-dicarboximide (PDI; a derivative with an analgesic activity) was studied in order to investigate its degradation mechanism and identify its degradation products in aqueous-organic solutions. The stability of PDI and its two degradation products (A and B) was performed with an HPLC method: (LiChrospher C18 column (250 x 4 mm LD., dp = 5 microm), mobile phase: 3.

The stability of N-[2-(4-o-fluorophenylpiperazin-1-yl)ethyl]-2,5-dimethyl-1 -phenylpyrrole-3,4-dicarboximide in aqueous-organic solutions.

The first-order reaction of solvolysis of N-[2-(4-o-fluorophenylpiperazin-1-yl)ethyl]-2,5-dimethyl-1-phenylpyrrole-3,4-dicarboximide (PDI) was investigated as a function of pH at 333, 328, 323, 318 and 308 K in the pH range 1.11 - 12.78.

Pyrido-1,2-thiazines and their in vitro antibacterial evaluation.

A series of known and newly synthesized pyrido-1,2-thiazine derivatives of type 3-6 were evaluated against strains of Mycobacterium fortuitum (PCM 672) and Staphylococcus aureus (PCM 2602) The pilot experiments showed that most of the compounds in initial in vitro microbiological evaluation were not efficient antibacterial agents, but unexpectedly promoted replication of the microorganisms in the range of 10-50%.

Antitumor in vitro evaluation of certain derivatives of pyrido-1,2-thiazines.

We report an antitumor in vitro evaluation of a small series of 3-phenyl(methyl)pyrazolo[4, 3-c] pyrido [3,2-e]-1,2-thiazines 4 and the related 3-benzoyl (acetyl)-4-hydroxypyrido [3,2-e]-1,2-thiazines 5 bearing a 3-(4-arylpiperazin-1-yl) propyl group at the nitrogen atom of the thiazine ring. Five of the seven pyridothiazines 5 tested and one compound from the series 4 (five compounds) exhibited in cell experiments a significant antitumor activity against several types of human tumor cells [GI50 values 3-54 mM/L]. The action of the most active compound 5f against some leukemia and melanoma cell lines was observed at sub mM/L doses at the GI50 level.

New derivatives of pyrrolo[3,4-d]pyridazinone and their anticancer effects.

Eighteen new derivatives of pyrrolo[3,4-d]pyridazinone modified at the pyrrole and pyridazine rings were synthesized and 12 of them were evaluated in vitro through anticancer screenings. The structures of new compounds were confirmed by elemental analysis and spectral data (IR, 1H NMR). None of the eight compounds assayed blocked the cell cycle regulating CDK1/cyclin B kinase, whereas two of the six compounds tested were active in anticancer screening at the cell experiments at a concentration of > or = 10(-5) M/l.

Antimycobacterial activity of some pyrido-1,2-thiazine derivatives.

The 3-benzoylpyrido-1,2-thiazine-1,1-dioxides 1 and the related pyrazolopyrido-1,2-thiazine-5,5-dioxides 2 with a 4-arylpiperazin-1-ylpropyl side chained by the nitrogen atom of the thiazine ring were evaluated in vitro against Myobacterium tuberculosis H37Rv. Some of the tested compounds proved to be potent antimycobacterial agents and for the most active of them (1a,b) minimum inhibitory concentrations (MIC = 3.13 and 6.