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Papers by Luiz Roberto Lopes Pinheiro
![Research paper thumbnail of SYNTHESIS AND ANTIVIRAL ACTIVITY OF NEW 4- (PHENYLAMINO)THIENO[2,3-b]PYRIDINE DERIVATIVES](https://attachments.academia-assets.com/88182444/thumbnails/1.jpg)
](Heterocyclic Communications, 2004
Several new 4-(phenylamino)thieno[2,3-f>]pyridines (6a-e) were synthesized and tested against her... more Several new 4-(phenylamino)thieno[2,3-f>]pyridines (6a-e) were synthesized and tested against herpes simplex virus type 1 (HSV-1). For the first time one compound (6a) of this heterocyclic system showed 86% of inhibitory indicating that these compounds retain antiviral potency in comparison to the parent pirazolo-pyridine derivatives. 5 The compounds thieno[2,3-i]pyridine (6) are structurally promising since it contains at least two motifs that could be easily modified: the thienopyridine and phenyl portions. Recently, a novel classes of thienopyrimidines and thienopyridines have been identified as potent inhibitors of VEGFR-2 kinase, which is the key component of the signaling pathway responsible for the sprouting and maturation of new blood vessels from tumors. 1 Also, a new series of thienopyrimidines were synthesized and studied as inhibitors of dihydrofolate reductase from Pneumocystis carinii, Toxoplasma gondii, Mycobacterium avium} The synthesis of thieno[2,3-6]pyridine was first reported in 1913 and represents only one of six possible isomers. 3 Their chemistry has been the subject of two reviews. 4 R-H. p-CH 3 , p-OCHj, <r OCH 3 , p-NOj R,-CH 3 , Ph Rj-CO2B. CO, H Since it was found that 4-anilino-l//-pyrazolo[3,4-£>]pyridine (7) derivatives are effective nonnucleoside inhibitor of reverse transcriptase enzyme (NNRI) of HIV-1, several studies have been made by us and other groups in order to investigate the structure-activity relationships of these compounds and to improve their antiviral activity. 5 " 7 Results and Discussion In pursuit of our goal of finding new antiviral lead compounds, we report the synthesis of ethyl 4-(phenylamino)thieno[2,3-i]pyridine-5-carboxylate (6a-e) analogues and evaluate their anti-HSV-1 activity. The synthetic route used for preparing 4-(phenylamino)thieno[2,3-6]pyridines (6a-e) from 5carboethoxy-4-chlorothieno[2,3-b]pyridine (5) is straightforward, and it was accomplished according to the reaction sequence outlined in Scheme l. 8 " 11 The bis-(2-thienylammonium)hexachlorostannate (1) was condensed with diethyl ethoxymethylenemalonate (2) to give ethyl a-carboethoxy-ß-(N-2-thienylammonium) acrylate (3). The cyclization of (3) was carried out by refluxing it in downtherm and isolating the ethyl 4hydroxythienopyridine-3-carboxylate (4) by precipitating from petroleum ether. By NMR analysis it was possible to observe that the hidroxy tautomer (4) predominates over the quinolone, which was easily chlorinated in refluxing phosphorus oxychloride producing 5-carboethoxy-4-chlorothieno[2,3-i]pyridine (5). For producing the target compounds an equimolar mixture of anilines and (5) were refluxed for two hours producing the new products, ethyl 4-(phenylamino)thieno[2,3-%yridine-5-carboxylate (6a-e), were isolated Received on July 25, 2004.
The American Journal of Cardiology, 1992
ABSTRACT Coronary angiography has been used as a gold standard for assessing the results of such ... more ABSTRACT Coronary angiography has been used as a gold standard for assessing the results of such interventional procedures as balloon angioplasty, atherectomy and laser angioplasty. However, it is still imprecise in defining the extent and composition of atheromatous plaques, and can underestimate the severity of disease process in an eccentric lesion.1,2 The introduction of intravascular ultrasound as an imaging modality for atherosclerotic coronary artery disease has opened a new field for studying the morphologic changes before and after interventional procedures. Because of the incorporation of high-frequency transducers, it is possible to obtain images of the coronary arterial wall and assess the structural composition of the diseased segments.3–5 With the increasing number of procedures and devices being developed currently to deal with atherosclerotic obstruction, there is a need for a technique that will permit accurate assessment of alterations in the luminal area, integrity of the intimal surface, and the presence or absence of ulcerated plaques and thrombi. The present study describes our initial experience in using intravascular ultrasound to evaluate stenosed saphenous vein grafts undergoing angioplasty.
Heterocyclic Communications, 2004
Several new 4-(phenylamino)thieno[2,3-f>]pyridines (6a-e) were synthesized and tested against her... more Several new 4-(phenylamino)thieno[2,3-f>]pyridines (6a-e) were synthesized and tested against herpes simplex virus type 1 (HSV-1). For the first time one compound (6a) of this heterocyclic system showed 86% of inhibitory indicating that these compounds retain antiviral potency in comparison to the parent pirazolo-pyridine derivatives. 5 The compounds thieno[2,3-i]pyridine (6) are structurally promising since it contains at least two motifs that could be easily modified: the thienopyridine and phenyl portions. Recently, a novel classes of thienopyrimidines and thienopyridines have been identified as potent inhibitors of VEGFR-2 kinase, which is the key component of the signaling pathway responsible for the sprouting and maturation of new blood vessels from tumors. 1 Also, a new series of thienopyrimidines were synthesized and studied as inhibitors of dihydrofolate reductase from Pneumocystis carinii, Toxoplasma gondii, Mycobacterium avium} The synthesis of thieno[2,3-6]pyridine was first reported in 1913 and represents only one of six possible isomers. 3 Their chemistry has been the subject of two reviews. 4 R-H. p-CH 3 , p-OCHj, <r OCH 3 , p-NOj R,-CH 3 , Ph Rj-CO2B. CO, H Since it was found that 4-anilino-l//-pyrazolo[3,4-£>]pyridine (7) derivatives are effective nonnucleoside inhibitor of reverse transcriptase enzyme (NNRI) of HIV-1, several studies have been made by us and other groups in order to investigate the structure-activity relationships of these compounds and to improve their antiviral activity. 5 " 7 Results and Discussion In pursuit of our goal of finding new antiviral lead compounds, we report the synthesis of ethyl 4-(phenylamino)thieno[2,3-i]pyridine-5-carboxylate (6a-e) analogues and evaluate their anti-HSV-1 activity. The synthetic route used for preparing 4-(phenylamino)thieno[2,3-6]pyridines (6a-e) from 5carboethoxy-4-chlorothieno[2,3-b]pyridine (5) is straightforward, and it was accomplished according to the reaction sequence outlined in Scheme l. 8 " 11 The bis-(2-thienylammonium)hexachlorostannate (1) was condensed with diethyl ethoxymethylenemalonate (2) to give ethyl a-carboethoxy-ß-(N-2-thienylammonium) acrylate (3). The cyclization of (3) was carried out by refluxing it in downtherm and isolating the ethyl 4hydroxythienopyridine-3-carboxylate (4) by precipitating from petroleum ether. By NMR analysis it was possible to observe that the hidroxy tautomer (4) predominates over the quinolone, which was easily chlorinated in refluxing phosphorus oxychloride producing 5-carboethoxy-4-chlorothieno[2,3-i]pyridine (5). For producing the target compounds an equimolar mixture of anilines and (5) were refluxed for two hours producing the new products, ethyl 4-(phenylamino)thieno[2,3-%yridine-5-carboxylate (6a-e), were isolated Received on July 25, 2004.
The American Journal of Cardiology, 1992
ABSTRACT Coronary angiography has been used as a gold standard for assessing the results of such ... more ABSTRACT Coronary angiography has been used as a gold standard for assessing the results of such interventional procedures as balloon angioplasty, atherectomy and laser angioplasty. However, it is still imprecise in defining the extent and composition of atheromatous plaques, and can underestimate the severity of disease process in an eccentric lesion.1,2 The introduction of intravascular ultrasound as an imaging modality for atherosclerotic coronary artery disease has opened a new field for studying the morphologic changes before and after interventional procedures. Because of the incorporation of high-frequency transducers, it is possible to obtain images of the coronary arterial wall and assess the structural composition of the diseased segments.3–5 With the increasing number of procedures and devices being developed currently to deal with atherosclerotic obstruction, there is a need for a technique that will permit accurate assessment of alterations in the luminal area, integrity of the intimal surface, and the presence or absence of ulcerated plaques and thrombi. The present study describes our initial experience in using intravascular ultrasound to evaluate stenosed saphenous vein grafts undergoing angioplasty.