Lajos Fodor - Academia.edu (original) (raw)
Papers by Lajos Fodor
6,7-Dimethoxy-2H-1,3-benzothiazine reacted with dimethyl acetylenedicarboxylate in aqueous methan... more 6,7-Dimethoxy-2H-1,3-benzothiazine reacted with dimethyl acetylenedicarboxylate in aqueous methanol to give heterocycles with unexpected structures. A mechanism is proposed for the reaction.
The title compounds (V), which cannot be obtained by direct oxidation of (I), are prepared using ... more The title compounds (V), which cannot be obtained by direct oxidation of (I), are prepared using the reversible formation of a dichloro-β-lactam moiety as novel protecting group. -(FODOR*, L.; CSOMOS, P.; CSAMPAI, A.; SOHAR, P.; Tetrahedron Lett. 51 (2010) 24, 3205-3207,
Tetrahedron Letters, 2011
A method for the synthesis of medium-sized 1,5-benzothiazocines by ring enlargement of 1,3-benzot... more A method for the synthesis of medium-sized 1,5-benzothiazocines by ring enlargement of 1,3-benzothiazines has been developed. When N-alkyl-1,3-benzothiazines were reacted with dimethyl acetylenedicarboxylate in acetonitrile at room temperature, regioisomeric 5,6-dihydro-2H-1,5-benzothiazocines and 5,6-dihydro-4H-1,5-benzothiazocines were obtained as novel ring systems. Dimethyl acetylenedicarboxylate could attack either the nitrogen or the sulfur atom of the thiazines. NMR spectroscopic and X-ray crystallographic investigations confirmed the
Tetrahedron Letters, 2011
The ring-enlargement reactions of monochloro-β-lactam-fused 2-aryl-1,3-benzothiazines revealed th... more The ring-enlargement reactions of monochloro-β-lactam-fused 2-aryl-1,3-benzothiazines revealed that the reactions of ortho-nitro aryl-substituted derivatives with sodium methoxide in methanol provided two products, depending on the amount of the base. With 2equiv of reagent, the expected 1,4-benzothiazepines were obtained. Somewhat surprisingly, treatment with a large excess of sodium methoxide led to the formation of indolo-1,4-benzothiazepines via a novel rearrangement. The structures
Crystengcomm, 2010
ABSTRACT The tautomers of 3-ethoxycarbonyl-2-phenyl-4,1-benzothiazepine and its 2-(4-methylphenyl... more ABSTRACT The tautomers of 3-ethoxycarbonyl-2-phenyl-4,1-benzothiazepine and its 2-(4-methylphenyl) and 2-(4-chlorophenyl) derivatives, identified in solution by spectroscopic means, could be separated in the form of single-crystals suitable for X-ray diffraction. This is at present a unique situation in the literature on desmotropy. For the three desmotropic pairs, the bond lengths and angles present in the puckered seven-membered rings are fairly consistent within each group of desmotropes, but differ between the imines and the enamines. The structural similarity within the imines is revealed best by the isostructurality of the methyl and chloro derivatives, while the puckering differences between the heterorings of the desmotropic groups are reminiscent of conformational polymorphism.
Orvosi hetilap, Jan 17, 2005
For the primary and secondary prevention of thromboembolic events are used the oral anticoagulant... more For the primary and secondary prevention of thromboembolic events are used the oral anticoagulants, the drugs having a low therapeutic index and frequent bleeding complication rate. Establishing the proper therapeutic dose of these drugs for different patients is complicated by a variety of conditions, such as the comorbidity, age, other drugs used, diet, and pharmacogenetic factors. One of the latters is the polymorphism of the cytochrome P450 CYP2C9 enzyme. The influence of CYP2C9 polymorphism on the effectiveness of the--in Hungary for oral anticoagulation exclusively used--acenocoumarol therapy and on the occurrence of bleeding complications was investigated. Genotyping of 421 patients including 183 men and 238 women, (mean age 66.2 +/- 11.8 years) who took acenocoumarol (Syncumar) for at least 6 months was performed. Based on anamnestic and laboratory data, the correlation between the genotype and the acenocoumarol dose and bleeding complications were retrospectively analysed. ...
Journal of Neurology, 2001
Objective The Leiden V mutation, which causes activated protein C resistance and thrombophilia, h... more Objective The Leiden V mutation, which causes activated protein C resistance and thrombophilia, has been found to be a risk factor for venous thrombosis. The angiotensin converting enzyme (ACE) D allele indirectly exerts an unfavourable effect on the vasoregulatory system. In this study, the frequency of these mutations was analysed in different subtypes of ischaemic stroke. Method and material According
Tetrahedron Letters, 2006
A novel procedure was developed for the preparation of 2,3-disubstituted 4,1-benzothiazepines, vi... more A novel procedure was developed for the preparation of 2,3-disubstituted 4,1-benzothiazepines, via the ring transformation of (2R * ,2aS * )-2-chloro-2a-phenyl-2,2a-dihydro-2H,4H-azeto[1,2-a][3,1]benzothiazin-1-one (1) with sodium ethoxide in ethanol. The tautomeric products (R * )-3-ethoxycarbonyl-2-phenyl-3,5-dihydro-4,1-benzothiazepine (4) and 3-ethoxycarbonyl-2-phenyl-1,5dihydro-4,1-benzothiazepine (5) exhibit the rare phenomenon of desmotropy of the condensed seven-membered heterocycles. Surprisingly, these desmotropes could be separated by column chromatography. The products are unexpectedly stable in solution and their structures were proved by means of NMR and mass spectrometry.
Tetrahedron Letters, 1995
... Britain 00404039 95 9.50+0.00 New Convenient Synthesis of 1,4Benzothiazepines Lajos Fodor*a, ... more ... Britain 00404039 95 9.50+0.00 New Convenient Synthesis of 1,4Benzothiazepines Lajos Fodor*a, Jinos Szab6,b Gibor Bernltthb, Pil Sohlrc aCentral Laboratory, County Hospital, H5701 Gyula, POB 46; blnstitute of Pharmaceutical Chemistry, Albert SzentGyiSrgyi Medical ...
Tetrahedron, 1981
Abstnct-6,7-Dimethoxy-2-pheny1-4&1,3-benzothiazine
Tetrahedron, 1984
6, 7-Dlmethoxy-Z_H-1.3~benzothlazine derivatives (
Tetrahedron, 2008
Quinoline analog 2-aryl-4H-3,1-benzothiazine derivatives 8–13, obtained by the condensation of o-... more Quinoline analog 2-aryl-4H-3,1-benzothiazine derivatives 8–13, obtained by the condensation of o-aminobenzyl chloride 1 with substituted thiobenzamides 2–7, were transformed to azeto[2,1-a][3,1]benzothiazin-1-one derivatives 18–23a,b,c and 24d,e by reaction with the corresponding substituted acetyl chlorides 14–17 in the presence of triethylamine. The structures of the new molecules were determined by NMR spectroscopy and electron ionization (EI) mass spectrometry. The typical EI+ mass spectrometric
Tetrahedron, 1992
Key Wordx 1~,lOb-Trisubstituted-8,9-~ethoxy-l,lOb-~y~~5~-l~~t~lo[4~][l~]~~~~~; cycloaddition of n... more Key Wordx 1~,lOb-Trisubstituted-8,9-~ethoxy-l,lOb-~y~~5~-l~~t~lo[4~][l~]~~~~~; cycloaddition of nitrilimines; reaction of 4-aryl-W-1,3-benzothiazines; conformational analysis.
NeuroMolecular Medicine, 2006
The renin-angiotensin system plays an important role in the maintenance of blood pressure homeost... more The renin-angiotensin system plays an important role in the maintenance of blood pressure homeostasis. The angiotensin-converting enzyme (ACE) converts angiotensin I into angiotensin II. Angiotensin II, which binds the angiotensin II type-1 receptor (AT1R), is a potent vasoconstrictor. On a pathophysiological basis, both ACE I/D and AT1R A1166C polymorphism lead to an enhanced activity of the angiotensin II-AT1R axis, thereby possibly contributing to circulatory disturbances. A mutually facilitatory effect may be presumed between the two polymorphisms. We examined whether this synergistic effect is involved in the evolution of different types of ischemic stroke. Genetic and clinical data on 308 consecutive patients with acutely developing ischemic stroke were analyzed. A total of 272 stroke and neuroimaging alteration-free subjects served as a control group. Univariate and logistic regression statistical approaches were used. The ACE D allele combined with the AT1R 1166C allele did not yield a risk of ischemic stroke. However, the co-occurrence of the homozygous ACE D/D and at least one AT1R 1166C allele was more frequent in the ischemic stroke group than in the control group (22.4 vs 11%, p < 0.005, OR, 2.33; 95% CI, 1.46-3.7). After specific subgroup analysis, this synergistic association was even stronger for small-vessel ischemic stroke (OR, 3.44; 95% CI, 1.9-6.24; p < 0.0005). Multivariate logistic regression analysis of the data confirmed this association (adjusted OR, 3.54, 95% CI, 1.88-7.16; p < 0.0005). Our results demonstrate that ACE D/D and AT1R 1166C NeuroMolecular Medicine
Monatshefte für Chemie - Chemical Monthly, 2010
Reactions of 1,3-Benzothiazines and 1,4-Benzothiazepines with Dimethyl Acetylenedicarboxylate. -N... more Reactions of 1,3-Benzothiazines and 1,4-Benzothiazepines with Dimethyl Acetylenedicarboxylate. -Novel heterocycles (III) and (V) are obtained unexpectedly. The exclusive Z-geometry of the carbomethoxymethylidene side-chain is proved by X-ray analysis of compound (IIIb) and analogy of NMR data. Possible reaction mechanisms are discussed in detail. -(FODOR*, L.; CSOMOS, P.; BERNATH, G.; SOHAR, P.; HOLCZBAUER, T.; KALMAN, A.; Monatsh.
Magnetic Resonance in Chemistry, 1989
Journal of Neurology, 2002
Ischemic stroke is a frequent heterogeneous multifactorial disease that is affected by several ge... more Ischemic stroke is a frequent heterogeneous multifactorial disease that is affected by several genetic mutations and environmental factors. We hypothesised the clinical importance of the co-occurrence of common, unfavorable genetic mutations in the development of different stroke subtypes. The Factor V Leiden G1691A (Leiden V), the prothrombin G20210A and the methylenetetrahydrofolate reductase C677T (MTHFR C677T) mutations and the angiotensin-converting enzyme I/D (ACE I/D) and apolipoprotein E (APOE) genotypes were examined by the PCR technique in 689 ischemic stroke patients and 652 stroke-free controls. Logistic regression models were used to estimate the relative risks of different stroke subtypes for different genotype combination patterns. The ACE D/D genotype alone or in combination with the MTHFR 677T or the APOE 4 allele or with both was highly specific for small-vessel infarction. The Leiden V mutation alone or in different combination patterns with the ACE D, APOE 4 and MTHFR 677T alleles was specifically predisposed to large-vessel infarction. The APOE 4 allele alone was calculated to be a general, minor genetic risk factor for ischemic stroke. The MTHFR 677T allele alone was not a risk factor for any stroke subtype. In the different specific predisposition gene combinations, however, both the APOE 4 and MTHFR 677T alleles could increase the relative risk of the given stroke subgroup. Common mutations which alone are minor or non-significant risk factors for ischemic stroke can yield, in specific combination patterns, a highly significant, moderate genetic risk of specific stroke subtypes.
Journal of Molecular Neuroscience, 2006
6,7-Dimethoxy-2H-1,3-benzothiazine reacted with dimethyl acetylenedicarboxylate in aqueous methan... more 6,7-Dimethoxy-2H-1,3-benzothiazine reacted with dimethyl acetylenedicarboxylate in aqueous methanol to give heterocycles with unexpected structures. A mechanism is proposed for the reaction.
The title compounds (V), which cannot be obtained by direct oxidation of (I), are prepared using ... more The title compounds (V), which cannot be obtained by direct oxidation of (I), are prepared using the reversible formation of a dichloro-β-lactam moiety as novel protecting group. -(FODOR*, L.; CSOMOS, P.; CSAMPAI, A.; SOHAR, P.; Tetrahedron Lett. 51 (2010) 24, 3205-3207,
Tetrahedron Letters, 2011
A method for the synthesis of medium-sized 1,5-benzothiazocines by ring enlargement of 1,3-benzot... more A method for the synthesis of medium-sized 1,5-benzothiazocines by ring enlargement of 1,3-benzothiazines has been developed. When N-alkyl-1,3-benzothiazines were reacted with dimethyl acetylenedicarboxylate in acetonitrile at room temperature, regioisomeric 5,6-dihydro-2H-1,5-benzothiazocines and 5,6-dihydro-4H-1,5-benzothiazocines were obtained as novel ring systems. Dimethyl acetylenedicarboxylate could attack either the nitrogen or the sulfur atom of the thiazines. NMR spectroscopic and X-ray crystallographic investigations confirmed the
Tetrahedron Letters, 2011
The ring-enlargement reactions of monochloro-β-lactam-fused 2-aryl-1,3-benzothiazines revealed th... more The ring-enlargement reactions of monochloro-β-lactam-fused 2-aryl-1,3-benzothiazines revealed that the reactions of ortho-nitro aryl-substituted derivatives with sodium methoxide in methanol provided two products, depending on the amount of the base. With 2equiv of reagent, the expected 1,4-benzothiazepines were obtained. Somewhat surprisingly, treatment with a large excess of sodium methoxide led to the formation of indolo-1,4-benzothiazepines via a novel rearrangement. The structures
Crystengcomm, 2010
ABSTRACT The tautomers of 3-ethoxycarbonyl-2-phenyl-4,1-benzothiazepine and its 2-(4-methylphenyl... more ABSTRACT The tautomers of 3-ethoxycarbonyl-2-phenyl-4,1-benzothiazepine and its 2-(4-methylphenyl) and 2-(4-chlorophenyl) derivatives, identified in solution by spectroscopic means, could be separated in the form of single-crystals suitable for X-ray diffraction. This is at present a unique situation in the literature on desmotropy. For the three desmotropic pairs, the bond lengths and angles present in the puckered seven-membered rings are fairly consistent within each group of desmotropes, but differ between the imines and the enamines. The structural similarity within the imines is revealed best by the isostructurality of the methyl and chloro derivatives, while the puckering differences between the heterorings of the desmotropic groups are reminiscent of conformational polymorphism.
Orvosi hetilap, Jan 17, 2005
For the primary and secondary prevention of thromboembolic events are used the oral anticoagulant... more For the primary and secondary prevention of thromboembolic events are used the oral anticoagulants, the drugs having a low therapeutic index and frequent bleeding complication rate. Establishing the proper therapeutic dose of these drugs for different patients is complicated by a variety of conditions, such as the comorbidity, age, other drugs used, diet, and pharmacogenetic factors. One of the latters is the polymorphism of the cytochrome P450 CYP2C9 enzyme. The influence of CYP2C9 polymorphism on the effectiveness of the--in Hungary for oral anticoagulation exclusively used--acenocoumarol therapy and on the occurrence of bleeding complications was investigated. Genotyping of 421 patients including 183 men and 238 women, (mean age 66.2 +/- 11.8 years) who took acenocoumarol (Syncumar) for at least 6 months was performed. Based on anamnestic and laboratory data, the correlation between the genotype and the acenocoumarol dose and bleeding complications were retrospectively analysed. ...
Journal of Neurology, 2001
Objective The Leiden V mutation, which causes activated protein C resistance and thrombophilia, h... more Objective The Leiden V mutation, which causes activated protein C resistance and thrombophilia, has been found to be a risk factor for venous thrombosis. The angiotensin converting enzyme (ACE) D allele indirectly exerts an unfavourable effect on the vasoregulatory system. In this study, the frequency of these mutations was analysed in different subtypes of ischaemic stroke. Method and material According
Tetrahedron Letters, 2006
A novel procedure was developed for the preparation of 2,3-disubstituted 4,1-benzothiazepines, vi... more A novel procedure was developed for the preparation of 2,3-disubstituted 4,1-benzothiazepines, via the ring transformation of (2R * ,2aS * )-2-chloro-2a-phenyl-2,2a-dihydro-2H,4H-azeto[1,2-a][3,1]benzothiazin-1-one (1) with sodium ethoxide in ethanol. The tautomeric products (R * )-3-ethoxycarbonyl-2-phenyl-3,5-dihydro-4,1-benzothiazepine (4) and 3-ethoxycarbonyl-2-phenyl-1,5dihydro-4,1-benzothiazepine (5) exhibit the rare phenomenon of desmotropy of the condensed seven-membered heterocycles. Surprisingly, these desmotropes could be separated by column chromatography. The products are unexpectedly stable in solution and their structures were proved by means of NMR and mass spectrometry.
Tetrahedron Letters, 1995
... Britain 00404039 95 9.50+0.00 New Convenient Synthesis of 1,4Benzothiazepines Lajos Fodor*a, ... more ... Britain 00404039 95 9.50+0.00 New Convenient Synthesis of 1,4Benzothiazepines Lajos Fodor*a, Jinos Szab6,b Gibor Bernltthb, Pil Sohlrc aCentral Laboratory, County Hospital, H5701 Gyula, POB 46; blnstitute of Pharmaceutical Chemistry, Albert SzentGyiSrgyi Medical ...
Tetrahedron, 1981
Abstnct-6,7-Dimethoxy-2-pheny1-4&1,3-benzothiazine
Tetrahedron, 1984
6, 7-Dlmethoxy-Z_H-1.3~benzothlazine derivatives (
Tetrahedron, 2008
Quinoline analog 2-aryl-4H-3,1-benzothiazine derivatives 8–13, obtained by the condensation of o-... more Quinoline analog 2-aryl-4H-3,1-benzothiazine derivatives 8–13, obtained by the condensation of o-aminobenzyl chloride 1 with substituted thiobenzamides 2–7, were transformed to azeto[2,1-a][3,1]benzothiazin-1-one derivatives 18–23a,b,c and 24d,e by reaction with the corresponding substituted acetyl chlorides 14–17 in the presence of triethylamine. The structures of the new molecules were determined by NMR spectroscopy and electron ionization (EI) mass spectrometry. The typical EI+ mass spectrometric
Tetrahedron, 1992
Key Wordx 1~,lOb-Trisubstituted-8,9-~ethoxy-l,lOb-~y~~5~-l~~t~lo[4~][l~]~~~~~; cycloaddition of n... more Key Wordx 1~,lOb-Trisubstituted-8,9-~ethoxy-l,lOb-~y~~5~-l~~t~lo[4~][l~]~~~~~; cycloaddition of nitrilimines; reaction of 4-aryl-W-1,3-benzothiazines; conformational analysis.
NeuroMolecular Medicine, 2006
The renin-angiotensin system plays an important role in the maintenance of blood pressure homeost... more The renin-angiotensin system plays an important role in the maintenance of blood pressure homeostasis. The angiotensin-converting enzyme (ACE) converts angiotensin I into angiotensin II. Angiotensin II, which binds the angiotensin II type-1 receptor (AT1R), is a potent vasoconstrictor. On a pathophysiological basis, both ACE I/D and AT1R A1166C polymorphism lead to an enhanced activity of the angiotensin II-AT1R axis, thereby possibly contributing to circulatory disturbances. A mutually facilitatory effect may be presumed between the two polymorphisms. We examined whether this synergistic effect is involved in the evolution of different types of ischemic stroke. Genetic and clinical data on 308 consecutive patients with acutely developing ischemic stroke were analyzed. A total of 272 stroke and neuroimaging alteration-free subjects served as a control group. Univariate and logistic regression statistical approaches were used. The ACE D allele combined with the AT1R 1166C allele did not yield a risk of ischemic stroke. However, the co-occurrence of the homozygous ACE D/D and at least one AT1R 1166C allele was more frequent in the ischemic stroke group than in the control group (22.4 vs 11%, p < 0.005, OR, 2.33; 95% CI, 1.46-3.7). After specific subgroup analysis, this synergistic association was even stronger for small-vessel ischemic stroke (OR, 3.44; 95% CI, 1.9-6.24; p < 0.0005). Multivariate logistic regression analysis of the data confirmed this association (adjusted OR, 3.54, 95% CI, 1.88-7.16; p < 0.0005). Our results demonstrate that ACE D/D and AT1R 1166C NeuroMolecular Medicine
Monatshefte für Chemie - Chemical Monthly, 2010
Reactions of 1,3-Benzothiazines and 1,4-Benzothiazepines with Dimethyl Acetylenedicarboxylate. -N... more Reactions of 1,3-Benzothiazines and 1,4-Benzothiazepines with Dimethyl Acetylenedicarboxylate. -Novel heterocycles (III) and (V) are obtained unexpectedly. The exclusive Z-geometry of the carbomethoxymethylidene side-chain is proved by X-ray analysis of compound (IIIb) and analogy of NMR data. Possible reaction mechanisms are discussed in detail. -(FODOR*, L.; CSOMOS, P.; BERNATH, G.; SOHAR, P.; HOLCZBAUER, T.; KALMAN, A.; Monatsh.
Magnetic Resonance in Chemistry, 1989
Journal of Neurology, 2002
Ischemic stroke is a frequent heterogeneous multifactorial disease that is affected by several ge... more Ischemic stroke is a frequent heterogeneous multifactorial disease that is affected by several genetic mutations and environmental factors. We hypothesised the clinical importance of the co-occurrence of common, unfavorable genetic mutations in the development of different stroke subtypes. The Factor V Leiden G1691A (Leiden V), the prothrombin G20210A and the methylenetetrahydrofolate reductase C677T (MTHFR C677T) mutations and the angiotensin-converting enzyme I/D (ACE I/D) and apolipoprotein E (APOE) genotypes were examined by the PCR technique in 689 ischemic stroke patients and 652 stroke-free controls. Logistic regression models were used to estimate the relative risks of different stroke subtypes for different genotype combination patterns. The ACE D/D genotype alone or in combination with the MTHFR 677T or the APOE 4 allele or with both was highly specific for small-vessel infarction. The Leiden V mutation alone or in different combination patterns with the ACE D, APOE 4 and MTHFR 677T alleles was specifically predisposed to large-vessel infarction. The APOE 4 allele alone was calculated to be a general, minor genetic risk factor for ischemic stroke. The MTHFR 677T allele alone was not a risk factor for any stroke subtype. In the different specific predisposition gene combinations, however, both the APOE 4 and MTHFR 677T alleles could increase the relative risk of the given stroke subgroup. Common mutations which alone are minor or non-significant risk factors for ischemic stroke can yield, in specific combination patterns, a highly significant, moderate genetic risk of specific stroke subtypes.
Journal of Molecular Neuroscience, 2006