ABSTRACT
Angiogenesis is a tightly regulated process that leads to the formation of new blood vessels sprouting from pre-existing microvasculature and occurs in limited physiological conditions or under pathological situations such as retinopathies, arthritis, endometriosis and cancer. Blockade of angiogenesis is an attractive approach for the treatment of such diseases. Particularly in malignancies, antiangiogenic therapy should be less toxic in comparison with conventional treatments such as chemotherapy, as angiogenesis is a process relatively restricted to the growing tumor. Vascular endothelial growth factor (VEGF) is one of the most important inducers of angiogenesis and exerts its cellular effects mainly by interacting with two high-affinity transmembrane tyrosine kinase receptors: VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1). It has been proven that inhibition of VEGF receptor activity reduces angiogenesis. For these reasons, the inhibition of VEGF or its receptor signalling system is an attractive target for therapeutic intervention. The most studied and developed inhibitors are monoclonal antibodies that neutralize VEGF, ribozymes, and small molecule VEGFR kinase inhibitors. Many important reviews dealing with VEGF-induced angiogenesis and its inhibition through the block of VEGF receptors have been reported, especially from a biological point of view. Here, we will review small synthetic VEGFR inhibitors that have appeared in literature in the last few years, focusing our attention on their medicinal chemistry in terms of chemical structure, mechanisms of action and structure-activity relationships. In fact, there have been an increased number of tyrosine kinase inhibitors in the most recent literature reports; their biological profile is extremely interesting and could be of great importance to medicinal chemists working in this area in improving their efficacy.
Subject(s)
Angiogenesis Inhibitors/pharmacology , Neoplasms/immunology , Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors , Receptors, Vascular Endothelial Growth Factor/chemistry , Animals , Chemistry, Pharmaceutical/methods , Drug Design , Humans , Indoles/pharmacology , Inhibitory Concentration 50 , Models, Chemical , Neoplasms/metabolism , Neoplasms/therapy , Neovascularization, Pathologic , Phthalimides/pharmacology , RNA, Catalytic/metabolism , Signal Transduction , Triazines/chemistry , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor Receptor-2/metabolism , ortho-Aminobenzoates/chemistryABSTRACT
New series of 5-alkoxy-benzopyranopyrimidine derivatives were developed from the chemical modulation of the substituent in position 2 of the scaffold, with the aim to produce analgesic/antiphlogistic agents more potent than analogues previously reported. The 2-hydrazino derivatives exhibited a good analgesic activity in writhing test; the analgesic doses of the compounds did not affect mice spontaneous locomotor activity thus any confounding sedative effect could be excluded. These derivatives revealed an aspirin-like profile with a strong inhibition of AA-induced platelet aggregation, probably due to a strong, non selective, inhibition of cyclooxygenases. In spite of the inhibition of COX activity displayed in vitro, the compounds did not cause gastric damage in rats after acute oral administration. A different pharmacological profile was observed for the 2-azido derivatives, particularly in vivo.
Subject(s)
Analgesics/chemical synthesis , Analgesics/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Pyrimidines/chemical synthesis , Pyrimidines/pharmacology , Acetic Acid , Analgesics/toxicity , Animals , Anti-Inflammatory Agents, Non-Steroidal/toxicity , Blood Platelets/drug effects , Carrageenan , Cyclooxygenase 1/metabolism , Cyclooxygenase 2 Inhibitors/chemical synthesis , Cyclooxygenase 2 Inhibitors/pharmacology , Cyclooxygenase Inhibitors/chemical synthesis , Cyclooxygenase Inhibitors/pharmacology , Edema/chemically induced , Edema/prevention & control , Fever/chemically induced , Fever/prevention & control , Humans , In Vitro Techniques , Indicators and Reagents , Lipopolysaccharides , Motor Activity/drug effects , Pain Measurement/drug effects , Platelet Aggregation Inhibitors/chemical synthesis , Platelet Aggregation Inhibitors/pharmacology , Pyrimidines/toxicity , Rabbits , Rats , Stomach Ulcer/chemically induced , Stomach Ulcer/pathology , Structure-Activity RelationshipABSTRACT
A series of N-methyl-N-pyrimidin-2-yl glycines 2a-e, having the pyrimidine ring fused with a cyclohexane [N-methyl-N-(5,6,7,8-tetrahydroquinazolin-2-yl)glycine], cyclohexene [N-methyl-N-(5,6-dihydroquinazolin-2-yl)glycine], 1,2,3,4-tetrahydronaphthalene [N-methyl-N-(5,6-dihydrobenzo[e]quinazolin-2-yl)glycine], benzopyrane [N-methyl-N-(5-phenyl-5H-[1]benzopyrano[4,3-d]pyrimidin-2-yl)glyci ne] and benzothiopyrane [N-methyl-N-(5H-[1]benzothiopyrano[4,3-d]pyrimidin-2-yl)glycine] ring, was prepared and tested for antiinflammatory activity. With the same purpose a number of N-5H-[1]benzopyrano[4,3-d]pyrimidin-2-yl substituted amino acids 3a-e, having a different chain length and branching were also synthesized and tested. All the described products 2 and 3 showed an appreciable antiphlogistic activity, particularly 2b and 2c.
Subject(s)
Amino Acids/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Pyrimidines/chemical synthesis , Amino Acids/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Carrageenan , Edema/chemically induced , Edema/prevention & control , Magnetic Resonance Spectroscopy , Pyrimidines/pharmacology , Rats , Spectrophotometry, InfraredABSTRACT
Some aliphatic and aromatic esters 2a-l were prepared starting from 5-aryl-1,2,4-triazoline-3-thiones bearing a 2-hydroxyethyl chain in position 2. The title compounds were evaluated for antipyretic and anti-inflammatory activities. Nearly all derivatives and in particular 2f, 2h, 2k exhibited antiphlogistic properties but were lacking in antipyretic activity.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Triazoles/chemical synthesis , Triazoles/pharmacology , Analgesics, Non-Narcotic/chemical synthesis , Analgesics, Non-Narcotic/chemistry , Analgesics, Non-Narcotic/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Esters , Magnetic Resonance Spectroscopy , Molecular Structure , Rats , Structure-Activity Relationship , Triazoles/chemistryABSTRACT
A series of 1,3,4-thiadiazol-2(3H)-ones (2a-j) with a nicotinoyl/isonicotinoyl group in position 3 and an aroylamino substituent in position 5 of the ring was prepared and evaluated for antipyretic and anti-inflammatory activities. All the title compounds and in particular 2e, 2i and 2j exhibited anti-inflammatory activity and were devoid of antipyretic properties.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Thiadiazoles/chemical synthesis , Thiadiazoles/pharmacology , Analgesics, Non-Narcotic/chemical synthesis , Analgesics, Non-Narcotic/chemistry , Analgesics, Non-Narcotic/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Magnetic Resonance Spectroscopy , Molecular Structure , Rats , Thiadiazoles/chemistryABSTRACT
The synthesis of 6-thiosubstituted 5-ethoxycarbonyl-1,3-diphenyl-2-thioxo-2,3-dihydropyrimidin- 4(1H)-ones 3, and of 6-substituted 5-hydroxy-1,3-diphenyl-2,3-dihydrothieno[2,3-d]pyrimidin-4(1H)-ones 5 and their esters 6 is described. These derivatives were prepared in order to evaluate the influence on the pharmacological profile of alkyl substituents bearing polar/hydrophilic functionalities at an enethiol substructure as in compounds 3 or to assess the effects arising from the incorporation of the sulfur atom in a thiophene moiety as in thienopyrimidinones 5 and 6 in comparison with a series of 5-substituted 6-acylthio-1,3-diphenyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-ones 1c,d, previously described. Preliminary screenings suggest that all tested compounds maintained or even increased the local anesthetic activity, but failed in the platelet antiaggregating activity; on the other hand, antiarrhythmic and antiinflammatory activity was preserved in some esters 6.
Subject(s)
Anesthetics, Local/chemical synthesis , Anti-Arrhythmia Agents/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Pyrimidinones/chemical synthesis , Anesthetics, Local/pharmacology , Animals , Anti-Arrhythmia Agents/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Edema/chemically induced , Edema/drug therapy , In Vitro Techniques , Mice , Pain Measurement/drug effects , Platelet Aggregation/drug effects , Pyrimidinones/pharmacology , RatsABSTRACT
A series of N-aryl substituted-1-aryl-3,4-diphenyl-5-pyrazole amines was synthesized and evaluated for antiinflammatory, antihypertensive and platelet antiaggregating activities. Several of them were found to exhibit a significant analgesic and antiarrhythmic activity.
Subject(s)
Amines/chemical synthesis , Analgesics, Non-Narcotic/chemical synthesis , Anti-Arrhythmia Agents/chemical synthesis , Pyrazoles/chemical synthesis , Amines/pharmacology , Analgesics, Non-Narcotic/pharmacology , Animals , Anti-Arrhythmia Agents/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antihypertensive Agents/chemical synthesis , Antihypertensive Agents/pharmacology , Magnetic Resonance Spectroscopy , Methylation , Mice , Pain Measurement/drug effects , Platelet Aggregation Inhibitors/chemical synthesis , Platelet Aggregation Inhibitors/pharmacology , Pyrazoles/pharmacology , Rats , Rats, Inbred SHRABSTRACT
Six series of N-acyl-N-phenyl ureas 1-6 of piperidine (1), and 2-ethyl- (2), 3-methyl- (3), 4-methyl- (4), 4-phenyl- (5), cis-2,6-dimethyl- (6) piperidine were synthesised and evaluated for their anti-inflammatory, anaesthetic, anti-pyretic properties. Some derivatives of series 1 and 5 were also assayed for anti-proliferative activity. Several compounds showed an anti-inflammatory activity comparable or slighty inferior to that of indomethacin in rats (1c,d, 2a,b,g,h, 3b, 4h, 5d,e). Moreover, an appreciable anti-inflammatory activity was also found in 2c,e, 3e,f,g, 4g, 5a,b,c,f,h, and 6a,b,d. All the compounds were devoid of anti-pyretic activity and only a few of them exhibited a low level of infiltration anaesthesia in mice. Compound 5a showed a broad spectrum anti-cancer activity (at low micromolar concentrations), particulary significant against leukemia subpanel.
Subject(s)
Anti-Inflammatory Agents/chemical synthesis , Piperidines/chemical synthesis , Analgesia , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Female , Humans , Male , Piperidines/chemistry , Piperidines/pharmacology , Tumor Cells, Cultured/drug effectsABSTRACT
A novel series of O-[2-hydroxy-3-(dialkylamino)propyl]ethers of (+)-camphor oxime was prepared and tested for its cardiovascular, analgesic and anti-inflammatory properties. No significant anti-inflammatory and hypotensive activities were displayed by any of the compounds, whereas several of them are reasonably active as antiarrhythmic and analgesic agents.
Subject(s)
Analgesics/chemical synthesis , Anti-Arrhythmia Agents/chemical synthesis , Bridged Bicyclo Compounds/chemical synthesis , Bridged Bicyclo Compounds/pharmacology , Oximes/chemical synthesis , Oximes/pharmacology , Acetates , Aconitine , Analgesics/pharmacology , Animals , Anti-Arrhythmia Agents/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antihypertensive Agents/chemical synthesis , Antihypertensive Agents/pharmacology , Arrhythmias, Cardiac/chemically induced , Arrhythmias, Cardiac/prevention & control , Edema/chemically induced , Edema/prevention & control , Magnetic Resonance Spectroscopy , Pain Measurement/drug effects , Rats , Ventricular Fibrillation/chemically induced , Ventricular Fibrillation/pathologyABSTRACT
A series of 2-aryl-6-methyl-3-phenylamino-6,7-dihydropyrano[4,3-c]pyrazol-4(2H )-ones were prepared and tested for antiinflammatory, analgesic, antipyretic, antiarrhythmic, antihypertensive and platelet antiaggregating activities. All of them showed an appreciable level of analgesic activity in mice.
Subject(s)
Analgesics, Non-Narcotic/chemical synthesis , Analgesics, Non-Narcotic/pharmacology , Animals , Mice , Pyrazoles/chemical synthesis , Pyrazoles/pharmacology , Rats , Structure-Activity RelationshipABSTRACT
The synthesis of N,N-disubstituted 3-(3,5-diphenyl-1H-pyrazol-1-yl)propanamides 2 a-d and 3-(3,5-diphenyl-1H-pyrazol-1-yl)propanamines 3 a-d starting from 3-(3,5-diphenyl-1H-pyrazol-1-yl)propanoic acid is described. Some of the above compounds showed considerable sedative and local anesthetic activities in mice, as well as a remarkable platelet antiaggregating activity in vitro. Moreover, the above compounds usually exhibited moderate analgesic and antiinflammatory activities in mice and rats, respectively.
Subject(s)
Amides/chemical synthesis , Anesthetics, Local/chemical synthesis , Hypnotics and Sedatives/chemical synthesis , Platelet Aggregation Inhibitors/chemical synthesis , Propylamines/chemical synthesis , Pyrazoles/chemical synthesis , Amides/pharmacology , Animals , Anti-Arrhythmia Agents/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Blood Pressure/drug effects , Heart Rate/drug effects , Humans , Hypoglycemic Agents/pharmacology , In Vitro Techniques , Mice , Motor Activity/drug effects , Propylamines/pharmacology , Pyrazoles/pharmacology , RatsABSTRACT
The synthesis of 1-acetyl-4-hydroxy-3,5-diphenyl-2-pyrazoline esters 3, 4-hydroxy-3,5-diphenyl-1H-pyrazole esters 5 and N-substituted 4-(3-amino-2-hydroxy-1-propoxy)-1-methyl-3,5-diphenyl-1H-pyrazoles 7, starting from 4-hydroxy-3,5-diphenyl-2-pyrazoline is described. Some of compounds 3, 5 and 7 showed a considerable antiarrhythmic and sedative activity in rats and mice, respectively, as well as a remarkable in vitro platelet antiaggregating activity. Moreover, the above compounds usually exhibited moderate antihypertensive, local anesthetic, analgesic and antiinflammatory activities in rats and mice.
Subject(s)
Anti-Arrhythmia Agents/chemical synthesis , Hypnotics and Sedatives/chemical synthesis , Platelet Aggregation Inhibitors/chemical synthesis , Pyrazoles/chemical synthesis , Analgesics/chemical synthesis , Analgesics/pharmacology , Anesthetics, Local/chemical synthesis , Anesthetics, Local/pharmacology , Animals , Antihypertensive Agents/chemical synthesis , Antihypertensive Agents/pharmacology , Esters/chemical synthesis , Esters/pharmacology , Humans , In Vitro Techniques , Mice , Motor Activity/drug effects , Pyrazoles/pharmacology , RatsABSTRACT
The synthesis of 1,3,3-trimethyl-N-[(2-pyridyl)methyl]-2- oxabicyclo [2.2.2]octan-6-amine (II) (exo, endo mixture) starting from 1,3,3-trimethyl-N-nitro-2-oxabicyclo [2.2.2]octan-6-imine (I), as well as of a series of amides (III) derived from the above amine, is described. Some compounds (III) showed remarkable depressant and antiarrhythmic activities in rats and mice, respectively, whereas the clofibric acid amide (III e) showed an appreciable hypolipidemic activity in rats. Moreover, the above compounds usually exhibited a moderate infiltration anesthesia in mice, as well as a weak hypotensive and bradycardic activity in rats.
Subject(s)
Amides/chemical synthesis , Anti-Arrhythmia Agents/chemical synthesis , Bridged Bicyclo Compounds/chemical synthesis , Bridged-Ring Compounds/chemical synthesis , Central Nervous System Depressants/chemical synthesis , Pyridines/chemical synthesis , Amides/pharmacology , Anesthetics, Local/chemical synthesis , Animals , Anticholesteremic Agents/chemical synthesis , Blood Pressure/drug effects , Bridged Bicyclo Compounds/pharmacology , Chemical Phenomena , Chemistry , Heart Rate/drug effects , Hypolipidemic Agents/chemical synthesis , Mice , Motor Activity/drug effects , Pyridines/pharmacology , RatsABSTRACT
A series of substituted 3-(arylamino)-4,5-dihydro-2H-benz[g]indazol-2-yl acetamides was synthesized and tested in comparison with former analogues. The title compounds showed only weak antiarrhythmic properties but good anti-inflammatory and antinociceptive activity, particularly evident in the morpholino derivative.
Subject(s)
Acetamides/pharmacology , Analgesics/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Acetamides/chemistry , Analgesics/chemistry , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Magnetic Resonance Spectroscopy , Molecular Structure , RatsABSTRACT
The synthesis of N-aryl-5(3)-phenyl-4-(3,5-diphenyl-1-pyrazolyl)-3(5)- pyrazoleamines 3 by reaction of some N-aryl-3-oxo-3-phenyl-2-(3,5-diphenyl-1- pyrazolyl)propanecarbothioamides with hydrazine is described. Also prepared were 4,5-dihydro-3-phenyl-4-(3,5-diphenyl-1-pyrazolyl)-1H-pyrazoles 6 and 1,6-dihydro-4-phenyl-5-(3,5-diphenyl-1-pyrazolyl)pyrimidines 7 by reaction of 1-phenyl-2-(3,5-diphenyl-1-pyrazolyl)-2-buten-1-one with hydrazine or guanidine and benzamidine, respectively. Some compounds 3, 6 and 7 showed remarkable antipyretic, antiinflammatory and in vitro platelet antiaggregating activities, as well as weak analgesic, antiarrhythmic, hypotensive and local anesthetic activities in rats and mice.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Pyrazoles/chemical synthesis , Pyrimidines/chemical synthesis , Anesthetics, Local/pharmacology , Animals , Anti-Arrhythmia Agents/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antihypertensive Agents/pharmacology , Blood Pressure/drug effects , Fever/chemically induced , Fever/prevention & control , Humans , In Vitro Techniques , Mice , Pain Measurement/drug effects , Platelet Aggregation Inhibitors/pharmacology , Pyrazoles/pharmacology , Pyrimidines/pharmacology , RatsABSTRACT
The synthesis of N-substituted 4,5(3)-diphenyl-3(5)-pyrazoleamines by reaction of N-substituted 3-oxo-2,3-diphenylpropane-carbothioamides with hydrazine is described. Some compounds showed remarkable antipyretic, antiarrhythmic and hypotensive activity in rats, as well as weak antiinflammatory, analgesic and in vitro platelet antiaggregating activity.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Antihypertensive Agents/chemical synthesis , Pyrazoles/chemical synthesis , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antihypertensive Agents/pharmacology , Blood Pressure/drug effects , Carrageenan , Edema/chemically induced , Edema/prevention & control , Fever/chemically induced , Fever/prevention & control , Magnetic Resonance Spectroscopy , Mice , Pain Measurement/drug effects , Platelet Aggregation Inhibitors/pharmacology , Pyrazoles/pharmacology , Rats , Spectrophotometry, Infrared , Ventricular Fibrillation/prevention & controlABSTRACT
The synthesis of 3-(arylamino)-6,7-dihydro-6-methylpyrano[4,3-c]pyrazol-4(1H or 2H)-ones by reaction of N-aryl-5,6-dihydro-4-hydroxy-6-methyl-2-oxo- 2H-pyrano-3-carbothioamides with hydrazine is described. Some compounds showed remarkable antipyretic, analgesic, antiarrhythmic and hypotensive activity in rats or mice, as well as weak antiinflammatory, local anesthetic and in vitro platelet antiaggregating activity.
Subject(s)
Analgesics/chemical synthesis , Anti-Arrhythmia Agents/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Antihypertensive Agents/chemical synthesis , Pyrazoles/chemical synthesis , Aconitine/antagonists & inhibitors , Analgesics/chemistry , Analgesics/pharmacology , Animals , Anti-Arrhythmia Agents/chemistry , Anti-Arrhythmia Agents/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antihypertensive Agents/chemistry , Antihypertensive Agents/pharmacology , Blood Pressure/drug effects , Humans , Mice , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/pharmacology , Pyrazoles/chemistry , Pyrazoles/pharmacology , RatsABSTRACT
A series of N-acyl-4,7,7-trimethyl-N-phenyl-3-(1-piperidinyl or dimethylamino)bicyclo[2.2.1]hept-2-ene-2-carbothioamides was prepared in excellent yields by reaction of 4,7,7-trimethyl-N-phenyl-3-(1-piperidinyl or dimethylamino)bicyclo[2.2.1]hept-2-ene-2-carbothioamides with a number of aromatic or heterocyclic acyl chlorides in dry pyridine solution and in the presence of sodium hydride. Some of the above compounds showed a platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid; moreover, some compounds exhibited moderate analgesic, antiinflammatory and hypotensive activities in mice or rats.
Subject(s)
Bridged Bicyclo Compounds/chemical synthesis , Piperidines/chemical synthesis , Platelet Aggregation Inhibitors/chemical synthesis , Thioamides/chemical synthesis , Acetylcholine/antagonists & inhibitors , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antihypertensive Agents/chemical synthesis , Antihypertensive Agents/pharmacology , Bridged Bicyclo Compounds/pharmacology , Guinea Pigs , Histamine H1 Antagonists/chemical synthesis , Histamine H1 Antagonists/pharmacology , Humans , In Vitro Techniques , Mice , Piperidines/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Rats , Thioamides/pharmacologyABSTRACT
The synthesis of 5-[[omega-(dialkylamino)alkoxy]methylene]-1,3,3-trimethyl-2- oxabicyclo[2.2.2]octan-6-ones by reaction of (+)-5-(hydroxymethylene)-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan- 6-one with a series of omega-(chloroalkyl)dialkylamines in the presence of potassium carbonate is described. Some compounds showed strong hypotensive, local anesthetic and antiarrhythmic activity in rats and mice, as well as moderate analgesic, antipyretic and in vitro platelet antiaggregating activity.
Subject(s)
Anesthetics, Local/chemical synthesis , Anti-Arrhythmia Agents/chemical synthesis , Antihypertensive Agents/chemical synthesis , Bridged Bicyclo Compounds/chemical synthesis , Analgesics, Non-Narcotic/chemical synthesis , Analgesics, Non-Narcotic/pharmacology , Anesthetics, Local/pharmacology , Animals , Anti-Arrhythmia Agents/pharmacology , Antihypertensive Agents/pharmacology , Bridged Bicyclo Compounds/pharmacology , Mice , Platelet Aggregation Inhibitors/chemical synthesis , Platelet Aggregation Inhibitors/pharmacology , RatsABSTRACT
The synthesis of 4-amino-3,5-diphenyl-1H-pyrazole-1-ethanol, as well as of their N-methyl, N-ethyl and N,N-dimethyl derivatives is described. A series of 1-(2-alkylaminoethyl)-3,5-diphenyl-1H-pyrazole-4-amines and of N-substituted 4-dimethylamino-3,5-diphenyl-1H-pyrazole-1-ethanamines were also prepared. Some of the above compounds showed remarkable local anesthetic, analgesic and in vitro platelet antiaggregating activities, as well as moderate antiinflammatory and antipyretic activities in rats and mice.