The beneficial effects of Cyclooxygenases (COX) inhibitors on human health have been known for th... more The beneficial effects of Cyclooxygenases (COX) inhibitors on human health have been known for thousands of years. Nevertheless, COXs, particularly COX-1, have been linked to a plethora of human diseases such as cancer, heart failure, neurological and neurodegenerative diseases only recently. COXs catalyze the first step in the biosynthesis of prostaglandins (PGs) and are among the most important mediators of inflammation. All published structural work on COX-1 deals with the ovine isoenzyme, which is easier to produce in milligram-quantities than the human enzyme and crystallizes readily. Here, we report the long-sought structure of the human cyclooxygenase-1 (hCOX-1) that we refined to an R/Rfree of 20.82/26.37, at 3.36 Å resolution. hCOX-1 structure provides a detailed picture of the enzyme active site and the residues crucial for inhibitor/substrate binding and catalytic activity. We compared hCOX-1 crystal structure with the ovine COX-1 and human COX-2 structures by using metri...
According to the World Health Organization, the major psychiatric and neurodevelopmental disorder... more According to the World Health Organization, the major psychiatric and neurodevelopmental disorders include major depression, bipolar disorder, schizophrenia, and autism spectrum disorder. The potential role of inflammation in the onset and progression of these disorders is increasingly being studied. The use of non-steroidal anti-inflammatory drugs (NSAIDs), well-known cyclooxygenase (COX) inhibitors, combined with first-choice specific drugs have been long investigated. The adjunctive administration of COX inhibitors to classic clinical treatments seems to improve the prognosis of people who suffer from psychiatric disorders. In this review, a broad overview of the use of COX inhibitors in the treatment of inflammation-based psychiatric disorders is provided. For this purpose, a critical analysis of the use of COX inhibitors in the last ten years of clinical trials of the major psychiatric disorders was carried out.
Microarray data are a kind of numerical non-negative data used to collect gene expression profile... more Microarray data are a kind of numerical non-negative data used to collect gene expression profiles. Since the number of genes in DNA is huge, they are usually high dimensional, therefore they require dimensionality reduction and clustering techniques to extract useful information. In this paper we use NMF, non-negative matrix factorization, to analyze microarray data, and also develop “intelligent” results visualization with the aim to facilitate the analysis of the domain experts. For this purpose, a case study based on the analysis of the gene expression profiles (GEPs), representative of the human multiple myeloma diseases, was investigated in 40 human myeloma cell lines (HMCLs). The aim of the experiments was to study the genes involved in arachidonic acid metabolism in order to detect gene patterns that possibly could be connected to the different gene expression profiles of multiple myeloma. NMF results have been verified by western blotting analysis in six HMCLs of proteins e...
Background:: Ovarian cancer is the second most common gynecologic malignancy, accounting for appr... more Background:: Ovarian cancer is the second most common gynecologic malignancy, accounting for approximately 220,000 deaths annually worldwide. Despite radical surgery and initial high response rates to platinum- and taxane-based chemotherapy, most patients experience a relapse, with a median progression-free survival of only 18 months. Overall survival is approximately 30% at 5 years from the diagnosis. In comparison, patients out from breast cancer are more than 80 % after ten years from the disease discovery. In spite of a large number of published fundamental and applied research, and clinical trials, novel therapies are urgently needed to improve outcomes of the ovarian cancer. The success of new drugs development in ovarian cancer will strongly depend on both fully genomic disease characterization and, then, availability of biomarkers able to identify women likely to benefit from a given new therapy. Methods:: In this review, the focus is given to describe how complex is the dis...
A multistep gram-scale synthesis of (S)-ethyl 2-(tert-butoxycarbonylamino)-3-(2-iodo-4,5-methylen... more A multistep gram-scale synthesis of (S)-ethyl 2-(tert-butoxycarbonylamino)-3-(2-iodo-4,5-methylenedioxyphenyl)propanoate (2) has been developed. The title compound was prepared starting from commercially available l-DOPA which was O- and N-protected before undergoing iodination by CF3CO2Ag/I2. The structure of the target compound was confirmed using IR, 1H-NMR, 13C-NMR, 2D (COSY, HSQC) NMR spectroscopy, as well as ESI-MS and HRMS.
Bisphosphonates (BPs) reduce bone pain and fractures by balancing the osteoblast/osteoclast ratio... more Bisphosphonates (BPs) reduce bone pain and fractures by balancing the osteoblast/osteoclast ratio. The behavior of ion channels in the presence of BPs is not known. To investigate this, the effect of zoledronic acid BP (ZOL) (3 × 10−8 to 5 × 10−4 M) treatment, on ion channels, cell proliferation, and mineralization, has been investigated on preosteoclast-like cells, RAW264.7, preosteoblast-like cells MC3T3-E1, and rat/mouse native bone marrow-derived osteoblasts. In whole-cell patch clamp on cell line- and bone marrow-derived osteoblasts, ZOL potentiated outward currents. On RAW264.7, ZOL (10−4 M)-evoked current was reduced by the Kv channel blocker tetraethylammonium hydrochloride (TEA), but not by the selective TRPV1-channel antagonist capsazepine. On MC3T3-E1 cells and bone marrow-derived osteoblasts, ZOL-evoked current (5 × 10−8 to 10−4 M) was reduced by capsazepine, whereas the selective TRPV1-channel agonist capsaicin potentiated the control current. In the cell proliferation ...
Activated microglia secrete an array of pro-inflammatory factors, such as prostaglandins, whose a... more Activated microglia secrete an array of pro-inflammatory factors, such as prostaglandins, whose accumulation contributes to neuronal damages. Prostaglandin endoperoxide synthases or cyclooxygenases (COX-1 and COX-2), which play a critical role in the inflammation, are the pharmacological targets of non-steroidal anti-inflammatory drugs, used to treat pain and inflammation. Since it was reported that COX-1 is the major player in mediating the brain inflammatory response, the aim of this study was to evaluate the effects of highly selective COX-1 inhibitors, such as P6 and mofezolac, in neuroinflammation models. Lipopolysaccharide (LPS)-activated mouse BV-2 microglial cells and LPS intracerebroventricular-injected mice as in vitro and in vivo neuroinflammation models, respectively, were used to probe the antiinflammatory efficacy of P6 and mofezolac. Both P6 and mofezolac reduce COX-1 expression in LPS-activated BV-2 cells. This reduction was accompanied with PGE2 release reduction an...
International journal of pharmaceutics, Jan 15, 2017
Two [19F]F-l-DOPA (F-DOPA) new β-cyclodextrin (CD)-based dosage forms (FA and FB, respectively) h... more Two [19F]F-l-DOPA (F-DOPA) new β-cyclodextrin (CD)-based dosage forms (FA and FB, respectively) have been studied and their physico-chemical and pharmacological features determined to overcome the administration site reactions showed by the currently used [18F]F-l-DOPA formulation (IASOdopa(®)) to perform PET-CT diagnosis in oncology (neuroendocrine tumors) and neurological (Parkinson's disease) field. Chemical stability of FA and FB was found to be longer than IASOdopa(®) by adding the thiol-antioxidant agent, L-Cysteine. (1)H and (19)F NMR investigations suggest the formation of an inclusion complex of F-DOPA with β-CD. In vitro experiments on the effects of FA and FB on mouse skeletal muscle fibers and on the human neuroblastoma SH-SY5Y and embryonal kidney tsA201 cell lines viability showed that FA was the most performant formulation compared to F-DOPA solutions. In vivo tolerability tests of FA on adult male rat showed no significant effects on body weight and no change in ...
A simple and efficient chemoenzymatic approach for the asymmetric synthesis of 1,3-diols and 2,4-... more A simple and efficient chemoenzymatic approach for the asymmetric synthesis of 1,3-diols and 2,4-disubstituted aryloxetanes has been established.
Novel compounds were prepared in fair to good yields as human beta(3)-adrenoceptor (beta(3)-AR) a... more Novel compounds were prepared in fair to good yields as human beta(3)-adrenoceptor (beta(3)-AR) agonists. In particular, aryloxypropanolamines 7 a-d (EC(50)=0.57-2.1 nM) and arylethanolamines 12 a,b,e (EC(50)=6.38-19.4 nM) were designed to explore the effects of modifications at the right-hand side of these molecules on their activity as beta(3)-AR agonists. Piperidine sulfonamides 15 a-c, e-g (EC(50)=6.1-36.2 nM) and piperazine sulfonamide derivatives 20-29 (EC(50)=1.79-49.3 nM) were examined as compounds bearing a non-aromatic linker on the right- and left-hand sides of the molecules. Some piperazine sulfonamides were found to be potent and selective beta(3)-AR agonists, even if the amine nitrogen atom is tertiary and not secondary, as is the case for all beta(3)-AR agonists reported so far. (S)-3-{4-{N-{4-{2-[2-Hydroxy-3-(4-hydroxyphenoxy)propylamino]ethyl}phenyl}sulfamoyl}phenoxy}propanoic acid (7 d; EC(50)=0.57 nM), (R)-N-{4-[2-(2-hydroxy-2-phenylethylamino)ethyl]phenyl}-4-(3-octylureido)benzenesulfonamide (12 e; EC(50)=6.38 nM), (R)-2-[1-(4-methoxyphenylsulfonyl)piperidin-4-ylamino]-1-phenylethanol (15 f; EC(50)=6.1 nM), and (S)-4-{2-hydroxy-3-[4-(4-methoxyphenylsulfonyl)piperazin-1-yl]propoxy}phenol (25; EC(50)=1.79 nM) were found to be the most potent beta(3)-AR agonists of the aryloxypropanolamine, arylethanolamine, piperidine sulfonamide, and piperazine sulfonamide classes, respectively. The two most potent compounds were identified as possible candidates for further development of beta(3)-AR agonists useful in the treatment of beta(3)-AR-mediated pathological conditions.
... a Dipartimento Farmaco-Chimico, Università degli Studi di Bari, Via E. Orabona 4, 70125 Bari,... more ... a Dipartimento Farmaco-Chimico, Università degli Studi di Bari, Via E. Orabona 4, 70125 Bari, Italy. b Istituto di Cristallografia (IC-CNR), Via Amendola 122/o, 70125 Bari, Italy. Received 11 July 2007; revised 5 September 2007; accepted 20 September 2007. ...
Biosynthesis of prostaglandins from arachidonic acid (AA) is catalyzed by cyclooxygenase (COX), w... more Biosynthesis of prostaglandins from arachidonic acid (AA) is catalyzed by cyclooxygenase (COX), which exists as COX-1 and COX-2. AA is in turn released from the cell membrane upon neopathological stimuli. COX inhibitors interfere in this catalytic and disease onset process. The recent prominent discovery involvements of COX-1 are mainly in cancer and inflammation. Five classes of COX-1 inhibitors are known up to now and this classification is based on chemical features of both synthetic compounds and substances from natural sources. Physicochemical interactions identification between such molecules and COX-1 active site was achieved through X-ray, mutagenesis experiments, specific assays and docking investigations, as well as through a pharmacometric predictive model building. All these insights allowed the design of new highly selective COX-1 inhibitors to be tested into those disease models in which COX-1 is involved. Particularly, COX-1 is expressed at high levels in the early to advanced stages of human epithelial ovarian cancer, and it also seems to play a pivotal role in cancer progression. The refinement of COX-1 selective inhibitor structure has progressed to the stage that some of the inhibitors described in this review could be considered as promising active principle ingredients of drugs and hence part of specific therapeutic protocols. This review aims to outline achievements, in the last 5 years, dealing with the identification of highly selective synthetic and from plant extracts COX-1 inhibitors and their theranostic use in neuroinflammation and ovarian cancer. Their gastrotoxic effect is also discussed.
ABSTRACT 3-Arylisoxazoles react with LDA in THF at 0°C affording syn-2,6-diaryl-3,7-diazatricyclo... more ABSTRACT 3-Arylisoxazoles react with LDA in THF at 0°C affording syn-2,6-diaryl-3,7-diazatricyclo[4.2.0.02,5]octan-4,8-diones (bis-azetidinones), via stereoselective dimerization of an azetinone anion intermediate. A fragmentation reaction affording arylnitriles may compete with electronic and steric effects of the substituent present in the aryl group being pivotal in determining the outcome of this reaction. An interesting behaviour with LDA of arylnitriles arising from the fragmentation reaction of some 3-arylisoxazoles was also observed. N,N-Diisopropylaminobenzonitriles were in fact formed (plausibly via a benzyne mechanism) from 3-(4-chlorophenyl)isoxazole and 3-(2-chlorophenyl)isoxazole, whereas 3-(2-methylphenyl)isoquinolin-1-amine was isolated starting from 3-(2-methylphenyl)isoxazole and LDA.
The beneficial effects of Cyclooxygenases (COX) inhibitors on human health have been known for th... more The beneficial effects of Cyclooxygenases (COX) inhibitors on human health have been known for thousands of years. Nevertheless, COXs, particularly COX-1, have been linked to a plethora of human diseases such as cancer, heart failure, neurological and neurodegenerative diseases only recently. COXs catalyze the first step in the biosynthesis of prostaglandins (PGs) and are among the most important mediators of inflammation. All published structural work on COX-1 deals with the ovine isoenzyme, which is easier to produce in milligram-quantities than the human enzyme and crystallizes readily. Here, we report the long-sought structure of the human cyclooxygenase-1 (hCOX-1) that we refined to an R/Rfree of 20.82/26.37, at 3.36 Å resolution. hCOX-1 structure provides a detailed picture of the enzyme active site and the residues crucial for inhibitor/substrate binding and catalytic activity. We compared hCOX-1 crystal structure with the ovine COX-1 and human COX-2 structures by using metri...
According to the World Health Organization, the major psychiatric and neurodevelopmental disorder... more According to the World Health Organization, the major psychiatric and neurodevelopmental disorders include major depression, bipolar disorder, schizophrenia, and autism spectrum disorder. The potential role of inflammation in the onset and progression of these disorders is increasingly being studied. The use of non-steroidal anti-inflammatory drugs (NSAIDs), well-known cyclooxygenase (COX) inhibitors, combined with first-choice specific drugs have been long investigated. The adjunctive administration of COX inhibitors to classic clinical treatments seems to improve the prognosis of people who suffer from psychiatric disorders. In this review, a broad overview of the use of COX inhibitors in the treatment of inflammation-based psychiatric disorders is provided. For this purpose, a critical analysis of the use of COX inhibitors in the last ten years of clinical trials of the major psychiatric disorders was carried out.
Microarray data are a kind of numerical non-negative data used to collect gene expression profile... more Microarray data are a kind of numerical non-negative data used to collect gene expression profiles. Since the number of genes in DNA is huge, they are usually high dimensional, therefore they require dimensionality reduction and clustering techniques to extract useful information. In this paper we use NMF, non-negative matrix factorization, to analyze microarray data, and also develop “intelligent” results visualization with the aim to facilitate the analysis of the domain experts. For this purpose, a case study based on the analysis of the gene expression profiles (GEPs), representative of the human multiple myeloma diseases, was investigated in 40 human myeloma cell lines (HMCLs). The aim of the experiments was to study the genes involved in arachidonic acid metabolism in order to detect gene patterns that possibly could be connected to the different gene expression profiles of multiple myeloma. NMF results have been verified by western blotting analysis in six HMCLs of proteins e...
Background:: Ovarian cancer is the second most common gynecologic malignancy, accounting for appr... more Background:: Ovarian cancer is the second most common gynecologic malignancy, accounting for approximately 220,000 deaths annually worldwide. Despite radical surgery and initial high response rates to platinum- and taxane-based chemotherapy, most patients experience a relapse, with a median progression-free survival of only 18 months. Overall survival is approximately 30% at 5 years from the diagnosis. In comparison, patients out from breast cancer are more than 80 % after ten years from the disease discovery. In spite of a large number of published fundamental and applied research, and clinical trials, novel therapies are urgently needed to improve outcomes of the ovarian cancer. The success of new drugs development in ovarian cancer will strongly depend on both fully genomic disease characterization and, then, availability of biomarkers able to identify women likely to benefit from a given new therapy. Methods:: In this review, the focus is given to describe how complex is the dis...
A multistep gram-scale synthesis of (S)-ethyl 2-(tert-butoxycarbonylamino)-3-(2-iodo-4,5-methylen... more A multistep gram-scale synthesis of (S)-ethyl 2-(tert-butoxycarbonylamino)-3-(2-iodo-4,5-methylenedioxyphenyl)propanoate (2) has been developed. The title compound was prepared starting from commercially available l-DOPA which was O- and N-protected before undergoing iodination by CF3CO2Ag/I2. The structure of the target compound was confirmed using IR, 1H-NMR, 13C-NMR, 2D (COSY, HSQC) NMR spectroscopy, as well as ESI-MS and HRMS.
Bisphosphonates (BPs) reduce bone pain and fractures by balancing the osteoblast/osteoclast ratio... more Bisphosphonates (BPs) reduce bone pain and fractures by balancing the osteoblast/osteoclast ratio. The behavior of ion channels in the presence of BPs is not known. To investigate this, the effect of zoledronic acid BP (ZOL) (3 × 10−8 to 5 × 10−4 M) treatment, on ion channels, cell proliferation, and mineralization, has been investigated on preosteoclast-like cells, RAW264.7, preosteoblast-like cells MC3T3-E1, and rat/mouse native bone marrow-derived osteoblasts. In whole-cell patch clamp on cell line- and bone marrow-derived osteoblasts, ZOL potentiated outward currents. On RAW264.7, ZOL (10−4 M)-evoked current was reduced by the Kv channel blocker tetraethylammonium hydrochloride (TEA), but not by the selective TRPV1-channel antagonist capsazepine. On MC3T3-E1 cells and bone marrow-derived osteoblasts, ZOL-evoked current (5 × 10−8 to 10−4 M) was reduced by capsazepine, whereas the selective TRPV1-channel agonist capsaicin potentiated the control current. In the cell proliferation ...
Activated microglia secrete an array of pro-inflammatory factors, such as prostaglandins, whose a... more Activated microglia secrete an array of pro-inflammatory factors, such as prostaglandins, whose accumulation contributes to neuronal damages. Prostaglandin endoperoxide synthases or cyclooxygenases (COX-1 and COX-2), which play a critical role in the inflammation, are the pharmacological targets of non-steroidal anti-inflammatory drugs, used to treat pain and inflammation. Since it was reported that COX-1 is the major player in mediating the brain inflammatory response, the aim of this study was to evaluate the effects of highly selective COX-1 inhibitors, such as P6 and mofezolac, in neuroinflammation models. Lipopolysaccharide (LPS)-activated mouse BV-2 microglial cells and LPS intracerebroventricular-injected mice as in vitro and in vivo neuroinflammation models, respectively, were used to probe the antiinflammatory efficacy of P6 and mofezolac. Both P6 and mofezolac reduce COX-1 expression in LPS-activated BV-2 cells. This reduction was accompanied with PGE2 release reduction an...
International journal of pharmaceutics, Jan 15, 2017
Two [19F]F-l-DOPA (F-DOPA) new β-cyclodextrin (CD)-based dosage forms (FA and FB, respectively) h... more Two [19F]F-l-DOPA (F-DOPA) new β-cyclodextrin (CD)-based dosage forms (FA and FB, respectively) have been studied and their physico-chemical and pharmacological features determined to overcome the administration site reactions showed by the currently used [18F]F-l-DOPA formulation (IASOdopa(®)) to perform PET-CT diagnosis in oncology (neuroendocrine tumors) and neurological (Parkinson's disease) field. Chemical stability of FA and FB was found to be longer than IASOdopa(®) by adding the thiol-antioxidant agent, L-Cysteine. (1)H and (19)F NMR investigations suggest the formation of an inclusion complex of F-DOPA with β-CD. In vitro experiments on the effects of FA and FB on mouse skeletal muscle fibers and on the human neuroblastoma SH-SY5Y and embryonal kidney tsA201 cell lines viability showed that FA was the most performant formulation compared to F-DOPA solutions. In vivo tolerability tests of FA on adult male rat showed no significant effects on body weight and no change in ...
A simple and efficient chemoenzymatic approach for the asymmetric synthesis of 1,3-diols and 2,4-... more A simple and efficient chemoenzymatic approach for the asymmetric synthesis of 1,3-diols and 2,4-disubstituted aryloxetanes has been established.
Novel compounds were prepared in fair to good yields as human beta(3)-adrenoceptor (beta(3)-AR) a... more Novel compounds were prepared in fair to good yields as human beta(3)-adrenoceptor (beta(3)-AR) agonists. In particular, aryloxypropanolamines 7 a-d (EC(50)=0.57-2.1 nM) and arylethanolamines 12 a,b,e (EC(50)=6.38-19.4 nM) were designed to explore the effects of modifications at the right-hand side of these molecules on their activity as beta(3)-AR agonists. Piperidine sulfonamides 15 a-c, e-g (EC(50)=6.1-36.2 nM) and piperazine sulfonamide derivatives 20-29 (EC(50)=1.79-49.3 nM) were examined as compounds bearing a non-aromatic linker on the right- and left-hand sides of the molecules. Some piperazine sulfonamides were found to be potent and selective beta(3)-AR agonists, even if the amine nitrogen atom is tertiary and not secondary, as is the case for all beta(3)-AR agonists reported so far. (S)-3-{4-{N-{4-{2-[2-Hydroxy-3-(4-hydroxyphenoxy)propylamino]ethyl}phenyl}sulfamoyl}phenoxy}propanoic acid (7 d; EC(50)=0.57 nM), (R)-N-{4-[2-(2-hydroxy-2-phenylethylamino)ethyl]phenyl}-4-(3-octylureido)benzenesulfonamide (12 e; EC(50)=6.38 nM), (R)-2-[1-(4-methoxyphenylsulfonyl)piperidin-4-ylamino]-1-phenylethanol (15 f; EC(50)=6.1 nM), and (S)-4-{2-hydroxy-3-[4-(4-methoxyphenylsulfonyl)piperazin-1-yl]propoxy}phenol (25; EC(50)=1.79 nM) were found to be the most potent beta(3)-AR agonists of the aryloxypropanolamine, arylethanolamine, piperidine sulfonamide, and piperazine sulfonamide classes, respectively. The two most potent compounds were identified as possible candidates for further development of beta(3)-AR agonists useful in the treatment of beta(3)-AR-mediated pathological conditions.
... a Dipartimento Farmaco-Chimico, Università degli Studi di Bari, Via E. Orabona 4, 70125 Bari,... more ... a Dipartimento Farmaco-Chimico, Università degli Studi di Bari, Via E. Orabona 4, 70125 Bari, Italy. b Istituto di Cristallografia (IC-CNR), Via Amendola 122/o, 70125 Bari, Italy. Received 11 July 2007; revised 5 September 2007; accepted 20 September 2007. ...
Biosynthesis of prostaglandins from arachidonic acid (AA) is catalyzed by cyclooxygenase (COX), w... more Biosynthesis of prostaglandins from arachidonic acid (AA) is catalyzed by cyclooxygenase (COX), which exists as COX-1 and COX-2. AA is in turn released from the cell membrane upon neopathological stimuli. COX inhibitors interfere in this catalytic and disease onset process. The recent prominent discovery involvements of COX-1 are mainly in cancer and inflammation. Five classes of COX-1 inhibitors are known up to now and this classification is based on chemical features of both synthetic compounds and substances from natural sources. Physicochemical interactions identification between such molecules and COX-1 active site was achieved through X-ray, mutagenesis experiments, specific assays and docking investigations, as well as through a pharmacometric predictive model building. All these insights allowed the design of new highly selective COX-1 inhibitors to be tested into those disease models in which COX-1 is involved. Particularly, COX-1 is expressed at high levels in the early to advanced stages of human epithelial ovarian cancer, and it also seems to play a pivotal role in cancer progression. The refinement of COX-1 selective inhibitor structure has progressed to the stage that some of the inhibitors described in this review could be considered as promising active principle ingredients of drugs and hence part of specific therapeutic protocols. This review aims to outline achievements, in the last 5 years, dealing with the identification of highly selective synthetic and from plant extracts COX-1 inhibitors and their theranostic use in neuroinflammation and ovarian cancer. Their gastrotoxic effect is also discussed.
ABSTRACT 3-Arylisoxazoles react with LDA in THF at 0°C affording syn-2,6-diaryl-3,7-diazatricyclo... more ABSTRACT 3-Arylisoxazoles react with LDA in THF at 0°C affording syn-2,6-diaryl-3,7-diazatricyclo[4.2.0.02,5]octan-4,8-diones (bis-azetidinones), via stereoselective dimerization of an azetinone anion intermediate. A fragmentation reaction affording arylnitriles may compete with electronic and steric effects of the substituent present in the aryl group being pivotal in determining the outcome of this reaction. An interesting behaviour with LDA of arylnitriles arising from the fragmentation reaction of some 3-arylisoxazoles was also observed. N,N-Diisopropylaminobenzonitriles were in fact formed (plausibly via a benzyne mechanism) from 3-(4-chlorophenyl)isoxazole and 3-(2-chlorophenyl)isoxazole, whereas 3-(2-methylphenyl)isoquinolin-1-amine was isolated starting from 3-(2-methylphenyl)isoxazole and LDA.
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Papers by Antonio Scilimati