- Synthesis and antihypertensive activity of some novel pyridazinones
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Four pyridazinones (2-5) were synthesized by the reaction of 3-benzoylpropionic acid with the corresponding hydrazines. These pyridazinones were further derivatized with appropriate aromatic aldehydes in the presence of piperidine to obtain the desired compounds (6-13). The chemical structures of the synthesized pyridazinones were elucidated on the basis of their spectral analysis (IR, 1H-NMR, and 13C-NMR). Molecular docking studies were carried out to identify the most active antihypertensive pyridazinone compound by using the crystal structure of human Angiotensin Converting Enzyme (ACE), the enzyme implicated in the pathogenesis of hypertension. The compound (6) was identified as the most active inhibitor of the Angiotensin Converting Enzyme (ACE). This compound was further assessed for its ACE inhibitory activity using Dojindo ACE Kit-WST test kit. The enzymatic ACE inhibitory activity revealed that the compound (6) had IC50 value of 5.78 μg/mL, wherein the standard drug Lisinopril had IC50 value of 0.85 μg/mL. It has been concluded that incorporation of free amino groups and free carboxylic acid groups in the structure of the synthesized pyridazinone (6-13) may provide more active and potent ACE inhibitors.
- Imran, Mohd,Nayeem, Naira
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- Synthesis of novel N-substitutedphenyl-6-oxo-3-phenylpyridazine derivatives as cyclooxygenase-2 inhibitors
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Some novel non-ulcerogenic N-substitutedphenyl-6-oxo-3-phenylpyridazines as COX-2 inhibitors have been developed (Supplementary material Appendix 1). The novel aldehyde 3 was prepared by reacting 6-phenylpyridazin-3(2H)-one with 4-fluorobenzaldehyde. The aldehyde 3 was reacted with different hydrazines and thiazolidin-4-ones to obtain the novel N-substitutedphenyl-6-oxo-3-phenylpyridazine derivatives. These were assessed for their anti-inflammatory potential and gastric ulcerogenic effects. The molecular docking investigations were also undertaken. The spectroscopic data were coherent with the allocated structures of the compounds. The compounds 4a (IC50 = 17.45 nm; p 50 = 17.40 nm; p 50 = 16.76 nm; p 50 = 17.15 nm; p 50 = 17.79 nm; p .05). These findings were consistent with the molecular docking investigations of 4a, 4b, 5a, and 10. The in vivo anti-inflammatory profile of 4a, 4b, 5a, and 10 was also superior to celecoxib and indomethacin. The compounds 4b, 5a, and 10 revealed no gastric ulcerogenic effects, wherein the compound 4a produced almost negligible gastric ulcerogenic effects than celecoxib and indomethacin. The compounds 4a, 4b, 5a, and 10 have been postulated as promising non-ulcerogenic COX-2 inhibitors.
- Khan, Abida,Diwan, Anupama,Thabet, Hamdy K,Imran, Mohd
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- Solubility and thermodynamics of 6-phenyl-4,5-dihydropyridazin-3(2H)-one in various neat solvents at different temperatures
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Pyridazinone derivatives have been investigated either pre-clinically or clinically in the treatment of various cardiovascular diseases. The main problems associated with these drugs are the poor aqueous solubility and toxicity. Therefore, in the current study, the solubility of pyridazinone derivative i.e. 6-phenyl-4,5-dihydropyridazin-3(2H)-one [coded as PDP-6] was determined in eleven different neat solvents at temperatures “T?=?293.2?K to 313.2?K” and “atmospheric pressure p?=?0.1?MPa”. Experimental mole fraction solubilities of PDP-6 were correlated well with van't Hoff and Apelblat models with mean percent deviation of ??1) followed by 2-(2-ethoxyethoxy) ethanol (Transcutol) (5.24?×?10??1), polyethylene glycol-400 [PEG-400] (8.47?×?10??2), ethyl acetate [EA] (1.45?×?10??2), ethylene glycol [EG] (1.09?×?10??2), propylene glycol [PG] (1.03?×?10??2), 2-butanol (7.78?×?10??3), 1-butanol (7.68?×?10??3), ethanol (6.96?×?10??3), isopropyl alcohol [IPA] (6.51?×?10??3) and water (1.61?×?10??6) and similar trend was also recorded at all five different temperatures investigated. “Apparent thermodynamic analysis” on mole fraction solubilities of PDP-6 indicated an endothermic dissolution of PDP-6 in all neat solvents studied. Based on these data, PDP-6 has been proposed as practically insoluble in water, sparingly soluble in ethanol, IPA, EG, PG, EA, 1-butanol and 2-butanol, soluble in PEG-400 and very soluble in DMSO and Transcutol.
- Imran, Mohd,Haq, Nazrul,Abida,Alanazi, Fars K.,Alsarra, Ibrahim A.,Shakeel, Faiyaz
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- An efficient synthesis of 4,5-dihydro-3(2H)-pyridazinone derivatives
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Reaction of hydrazine with 5-(2-aryl-2-oxo-ethan-1-yl)-5-R Meldrum's acids 3 gives 4,6-disubstituted 4,5-dihydropyridazin-3(2H)-ones 4 at room temperature. The method is simple and the yield is good. The production of the starting material 3 also is discu
- Toth, Gyoergy,Molnar, Sandor,Tamas, Tivadar,Borbely, Ildiko
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- Synthesis of 1,2,4-triazolopyridazines, isoxazolofuropyridazines, and tetrazolopyridazines as antimicrobial agents
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Through current and previous researches, it was found that the derivatives of pyridazine, isoxazole, tetrazole, quinazoline, hydrazinyl, and 1,2,4-triazole have many pharmacological activities. Thus, a series of novel furopyridazinones (7), isoxazolopyridazine (8), sub-benzylidene-furopyridazinones (9a-c), isoxazolofuropyridazines (10a-c), 3-chloro-(pyridin-4-ylmethylene)-dihydropyridazines (11), tetrazolopyridazines (12), pyridazinoquinazolinones (13), piperazinyl/morpholino-pyridazines (14a,b), hydrazinyl-pyridazines (15), and 1,2,4-triazolo-pyridazines (16a,b) in good yields (72%-90%) were synthesized from substituted ethyl 4-oxo-4-phenylbutanoate (2), 6-phenyl-4,5-dihydropyridazinone (3), and 6-phenyl-4-(pyridin-4-ylmethylene)-4,5-dihydropyridazinone (4) as beginning materials. All the chemical structures of the new compounds have been demonstrated by different spectroscopy analyses such as infrared, NMR, mass spectrum, and elemental analysis. Also, the activities of the newly prepared compounds were tested against many types of bacteria and fungi in vitro. Hence, 1,2,4-triazolopyridazines (16a,b), isoxazolofuropyridazines (10a-c), tetrazolopyridazines (12), Piperazinyl/morpholinyl-pyridazines (14a,b) displayed the most efficient antimicrobial activities compared with the cefotaxime sodium and nystatin as standard drugs.
- Abu-Hashem, Ameen A.,Fathy, Usama,Gouda, Moustafa A.
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- Conversion of γ-bicyclic lactams to 4,5-dihydro-2H-pyridazin-3-ones
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Bicyclic lactams are uniquely suited as precursors for the synthesis of chiral substituted 4,5-dihydro-2H-pyridazinones. This paper describes the development of a method for the direct conversion of unsubstituted and 4-substituted γ-bicyclic lactams to 4,5-dihydro-2H-pyridazin-3-ones and 2-phenyl-4,5-dihydro-2H-pyridazin-3-ones.
- Lim, Yu Jin,Angela, Mia,Buonora, Paul T.
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- Brine Shrimp (Artemia salina) Lethality Bioassay of Some 2-(Alkyl/Aryl)-6-Phenyl-4,5-Dihydropyridazin-3(2H)-one Derivatives
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A series of pyridazinone derivatives, 2-(alkyl/aryl)-6-phenyl-4,5-dihydropyridazin-3(2H)-ones (3a-h), was synthesized from 6-phenyl-4,5-dihydropyridazin-3(2H)-one (2). Compound 2 was synthesized from benzoylpropionic acid (1). The synthesized compounds were characterized on the basis of their spectral (infrared, proton nuclear magnetic resonance, carbon-13 nuclear magnetic resonance, and mass spectra) and elemental analytical data. The compounds 2 and 3a-h and potassium dichromate (as reference drug) were tested at the dose level of 10, 20, and 30 μg/mL. Compounds 3d and 3b exhibited potent brine shrimp lethality with LC50values of 4.023 μg and 4.20 μg. Other compounds 3g, 3f, 3c, 3h, 2, 3a, and 3e also showed significant cytotoxic activity with LC50values of 13.91, 12.58, 11.91, 11.76, 10.58, 9.76, and 7.46 μg, respectively. The present study supports that brine shrimp bioassay is a simple, reliable, and suitable method for estimation of bioactivity of synthesized compounds and provides support for their use in medicine.
- Acharya, Mrityunjoy,Asif, Mohammad,Imran, Mohd,Kamal, Mehnaz
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- Synthesis, anti-convulsant activity and molecular docking study of novel thiazole pyridazinone hybrid analogues
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Pyridazinone analogues have been known to be potential candidates for anticonvulsant agents. We have identified several pyridazinone-based anticonvulsant agents. As a continuation to our previous research, a series of hybrid pyridazinone-thiazole connected through amide linkage were designed and synthesized. Among these, compound SP-5F demonstrated significant anticonvulsant activity with median effective dose of 24.38 mg/kg (MES) and 88.23 mg/kg (scPTz). Results of GABA estimation showed a marked increase in the GABA level when compared with control. Molecular docking studies at the active site of GABA receptor, further confirmed the GABA modulatory effects of SP-5F.
- Khisal, Subuhi,Mishra, Ravinesh,Partap, Sangh,Siddiqui, Aness Ahmad,Yar, Mohammad Shahar
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- Design, Synthesis, and Pharmacological Screening of Pyridazinone Hybrids as Anticonvulsant Agents
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A series of new hybrid benzimidazole containing pyridazinones derivatives were designed and synthesized in accordance with the pharmacophoric requirements essential for the anticonvulsant activity. The synthesized compounds were evaluated for anticonvulsant activity on mice by the gold standard maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ)-induced seizure models. Among the compounds tested, SS-4F showed significant anticonvulsant activity in both the screens with ED50 values of 25.10 and 85.33 mg/kg in the MES and scPTZ screens, respectively. Compound SS-4F emerged as safer and effective anticonvulsant due to its several-fold higher protective indices. Further, the gamma-aminobutyric acid (GABA) estimation result showed a marked increase in the GABA level (1.7-fold) as compared to the control, which was further confirmed by good binding properties with the GABAA receptor.
- Partap, Sangh,Yar, Mohammad Shahar,Hassan, Md. Zaheen,Akhtar, Md. Jawaid,Siddiqui, Anees A.
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- Efficient synthesis, anticonvulsant and muscle relaxant activities of new 2-((5-amino-1,3,4-thiadiazol-2-yl)methyl)-6-phenyl-4,5-dihydropyridazin-3(2H) -one derivatives
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A series of 2-(2-(3-(4-chlorophenyl)-6-oxo-5,6-dihydropyridazin-1(4H)yl) acetyl)hydrazine carbothioamide and 2-((5-amino-1,3,4-thiadiazol-2-yl)methyl)-6- (4-chlorophenyl)-4,5-dihydropyridazin-3(2H)-one derivatives were synthesized, characterized, and evaluated for anticonvulsant activity and muscle relaxant activity. The synthesized compounds 5d (82.75 %) and 5e (85.44 %) showed promising anticonvulsant activity by protection against tonic hind limb extensor phase in maximal electroshock model (MES) at (50 mg/kg) compared to standard drug phenytoin and also compounds 5d (82.75 %), and 5e (85.44 %) showed significant anticonvulsant activity by protection against pentylenetetrazole- induced generalized convulsions in pentylenetetrazole model (PTZ) at (100 mg/kg) compared to standard drug diazepam. On the other hand, compound 5e showed significant muscle relaxant activity (84.57 %) by rotarod and traction test model comparing with diazepam as a standard drug.
- Sharma, Bhawna,Verma, Amita,Sharma, Upendra Kumar,Prajapati, Sunil
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p. 146 - 157
(2014/03/21)
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- Design, synthesis and antihypertensive screening of novel pyridazine substituted s-triazin-2-imine/one/thione derivatives
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Some new 7-substituted-phenyl-3,4,8,9-tetrahydro-2H-pyridazino[1,6-a][1,3,5]triazin-2-imine/one/thione derivatives were synthesized by a sequence of reactions starting from appropriate aryl hydrocarbons. The final compounds were screened for antihypertensive activities by non-invasive method using Tail Cuff method. All the test compounds showed significant antihypertensive activity; 7-(biphenyl-4-yl)-3,4,8,9-tetrahydro-2H-pyridazino[1,6-a][1,3,5]triazin-2-imine (4p) exhibited antihypertensive activity more than the reference standard drugs.
- Mishra, Ravinesh,Siddiqui, Anees A.,Husain, Asif,Rashid, Mohd.,Goda, Chirag
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p. 552 - 559
(2015/02/19)
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- A copper-catalyzed aerobic cascade dehydrogenative- dehalogenative reaction
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A copper-catalyzed cascade dehydrogenative and dehalogenative reaction of halogenated 6-phenyl-4,5-dihydropyridazin-3(2H)-ones to 6-phenylpyridazin-3(2H)- ones has been developed. Moreover, the catalytic system consisting of copper(II) acetate/sodium carbonate/pyridine exhibits high reactivity and selectivity with oxygen as the terminal oxidant. Copyright
- Liang, Lei,Yang, Guanyu,Wang, Wei,Xu, Fengrong,Niu, Yan,Sun, Qi,Xu, Ping
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p. 1284 - 1290
(2013/06/26)
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- Design, synthesis and antihypertensive screening of novel pyridazine substituted s-triazin-2-imine/one/thione derivatives
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Some new 7-substituted-phenyl-3,4,8,9-tetrahydro-2H-pyridazino[1,6-a][1,3, 5]triazin-2-imine/one/thione derivatives were synthesized by a sequence of reactions starting from appropriate aryl hydrocarbons. The final compounds were screened for antihypertensive activities by non-invasive method using Tail Cuff method. All the test compounds showed significant antihypertensive activity; 7-(biphenyl-4-yl)-3,4,8,9-tetrahydro-2H-pyridazino[1,6-a][1,3,5]triazin-2-imine (4p) exhibited antihypertensive activity more than the reference standard drugs.
- Mishra, Ravinesh,Siddiqui, Anees A.,Husain, Asif,Rashid, Mohd.,Goda, Chirag
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p. 552 - 559
(2013/05/08)
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- Anticonvulsant and antitubercular activities of 6-Phenyl/Biphenyl-4-yl-2- [2-(pyridin-2-ylamino)-ethyl]-and 6-(Biphenyl-4yl)-2-(2N-subtituted amin-1-yl)-ethyl derivatives of 4,5-dihydropyridazin-3(2H)-one
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Some 6-Phenyl/Biphenyl-4-yl-2-[2-(pyridin-2-ylamino)-ethyl]/-2-(2N- subtituted amin-1-yl)-ethyl-4,5- dihydropyridazin-3(2H)-one (4a-h) were synthesized by reacting 6-phenyl/biphenyl-4,5-dihydropyridazin-3(2H)-one with bromoethyl derivatives of cyclic secondary amines and 2-aminopyridine. All the compounds, 4a-h, were evaluated as anticonvulsant by using maximum electro shock (MES) and isoniazid (INH) induced convulsion methods at 50mg/kg dose level, and as antitubercular by Microplate Almar Blue Assay (MABA) method. In anticonvulsant activity, phenytoin (25mg/kg) and sodium vaproate (50mg/kg) were used as reference drugs. All compounds (4a-h) showed significant anticonvulsant activities against both MES and INH methods, and compound g showed highest activity against MES method. In antitubercular activity, compounds 4c-4h showed 25 μg/ml MIC value, and compounds 4a-4b exhibited 50 μg/ml MIC value when compared with reference drugs [isoniazid (3.125 μg/ml), pyrizinamide (3.125μg/ml)] and (streptomycin 6.25μg/ml) MIC values, and found less potent than the reference drugs.
- Asif, Mohammad,Singh, Anita,Lakshmayya,Husain, Asif,Siddiqui, Anees A.
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p. 651 - 660
(2013/08/23)
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- Further studies on 2-arylacetamide pyridazin-3(2H)-ones: Design, synthesis and evaluation of 4,6-disubstituted analogs as formyl peptide receptors (FPRs) agonists
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Formyl peptide receptors (FPRs) play an essential role in the regulation of endogenous inflammation and immunity. In the present studies, a large series of pyridazin-3(2H)-one derivatives bearing an arylacetamide chain at position 2 was synthesized and te
- Giovannoni, Maria Paola,Schepetkin, Igor A.,Cilibrizzi, Agostino,Crocetti, Letizia,Khlebnikov, Andrei I.,Dahlgren, Claes,Graziano, Alessia,Dal Piaz, Vittorio,Kirpotina, Liliya N.,Zerbinati, Serena,Vergelli, Claudia,Quinn, Mark T.
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p. 512 - 528
(2013/07/27)
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- Iodine-mediated facile dehydrogenation of dihydropyridazin-3(2H)one
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A new protocol for the dehydrogenation of dihydropyridazin-3(2H)-one has been carried out by catalytic amount of iodine in dimethyl sulphoxide in good yield with easy workup.
- Humne, Vivek T.,Konda, Shankaraiah G.,Hasanzadeh, Kamal,Lokhande, Pradeep D.
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scheme or table
p. 1435 - 1438
(2012/06/01)
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- Synthesis, characterization and antihypertensive activity of pyridazinone derivatives
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Some 6-(substituted-phenyl)-2-(substitutedmethyl)-4,5-dihydropyridazin-3(2H)-one derivatives were synthesized by reacting 6-substituted-phenyl-4,5-dihydropyridazin-3(2H)-one with cyclic secondary amine under Mannich reaction conditions. The final compounds (15-70) were evaluated for antihypertensive activities by non-invasive method using Tail Cuff method. The compounds 16, 19, 24, 30, 39, 42 and 45 showed good antihypertensive activity.
- Siddiqui, Anees A.,Mishra, Ravinesh,Shaharyar, Mohammad
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scheme or table
p. 2283 - 2290
(2010/07/05)
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- Synthesis and antimicrobial activity of some novel oxadiazole derivatives
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A series of 5-{3′-oxo-6′-(substituted aryl)-2′,3′, 4′,5′-tetrahydropyridazin-2′-ylmethyl}-2-substituted 1,3,4-oxadiazole has been synthesized. Appropriate aromatic hydrocarbon reacts with succinic anhydride in the presence of AlCl3 to yield β-aroyl propionic acid (1a). The corresponding acid is cyclized with hydrazine hydrate to give 6-(substituted aryl)-2,3,4,5-tetrahydro-3-pyridazinone (1b).This ntermediate after reaction with ethyl bromoacetate, was hydrazinolyzed into 3-oxo-6-(substituted aryl)-2, 3, 4, 5-tetrahydropyridazinyl acetohydrazide (1c).The resulting product was converted into 5-{3′-oxo-6′-(substituted aryl)-2′,3′,4′,5′- tetrahydropyridazin-2′-ylmethyl]-2-substituted 1,3,4-oxadiazole (Scheme 1). All the final compounds were structurally elucidated on the basis of IR, 1H-NMR, MS data and elemental analysis and screened for antibacterial, antifungal and antitubercular activity. All the compounds are evaluated for their antibacterial activity against E. coli, S. aureus, Miavcoccus luteus and Klebsiella pneumoniae by using cup plate technique in the nutrient agar at 100 μg/mL concentration. Antitubercular activity was determined using the BACTEC 460 system. Stock solutions of test compounds were prepared in DMSO. MIC of rifampin was calculated by established procedures.All the synthesized compounds were screened at 6.25 μg/mL against M. tuberculosis H37 Rv comparable with that of standard rifampicin and isoniazid. All the final compounds were evaluated for antifungal activity against C. albicans and C. neoformans by using cup-plate method in the Sabouraud agar media The zone of inhibition (mm) of each compound was determined and compared with standard drug fluconazole.
- Islam, Mojahidul,Siddiqui, Anees A.,Rajesh, Ramadoss,Bakht, Afroz,Goyal, Sunil
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experimental part
p. 441 - 447
(2009/04/07)
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- Synthesis, antitubercular, antifungal and antibacterial activities of 6-substituted phenyl-2-(3′-substituted phenyl pyridazin-6′-yl)-2,3, 4,5-tetrahydropyridazin-3-one
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A series of 6-substituted phenyl-2-(3′-substituted phenyl pyridazin-6′-yl)-2,3,4,5-tetrahydropyridazin-3-ones has been synthesized. An appropriate aromatic hydrocarbon reacts with succinic anhydride in presence of AlCl3 to yield β-aroyl propionic acid. The corresponding acid was cyclized with hydrazine hydrate to give 6-(substituted aryl)-2,3,4,5- tetrahydro-3-pyridazinone, which was heated on steam bath with phosphorus( V) oxychloride to yield 3-chloro 6-substituted phenyl pyridazine. This intermediate after reaction with hydrazine hydrate was converted into 3-hydrazino-6- substituted phenyl pyridazine. The resulting product was converted into 6-substituted phenyl-2-(3′-substituted phenyl pyridazin-6′-yl)-2,3, 4,5-tetrahydropyridazin-3-one by reacting with substituted aroyl propionic acid. Spectral data (IR, NMR, mass spectra) confirmed the structures of the synthesized compounds. The synthesized compounds were investigated for their in vitro antitubercular, antifungal and antibacterial activities. The results indicated that the synthesized compounds have mild to potent activities with reference to their appropriate reference standards.
- Islam, Mojahidul,Siddiqui, Anees A.,Rajesh, Ramadoss
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experimental part
p. 353 - 362
(2009/04/11)
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- Synthesis and in-vitro antifungal activity of 6-substituted-phenyl-2- {[(4′-substituted phenyl-5′-thioxo)-1,2,4-triazol-3-yl]-methyl}-2,3, 4,5-tetrahydropyridazin-3-one derivatives
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The synthetic pathway for 6-substituted phenyl-2-[{(4′-substituted phenyl-5′-thioxo)-1,2,4-triazol-3-yl}-methyl]-2,3,4,5-tetrahydropyridazin- 3-one compounds was achieved by a sequence of reactions starting from respective aryl hydrocarbons and is illustrated in Scheme1. All the compounds were tested for their in vitro antifungal activity on five fungal species, namely Candida albicans, Trichophyton rubrum, Aspergillus flavus, Aspergillus niger and Penicillium citrinium. The chloro substituent derivative (compound 5g) showed the highest activity against all the fungal species. The MIC of the standard drug voriconazole was between 0.10 - 0.40 μg/mL against all the fungal species except A. fumigatus. The two electronegative groups of Cl were increasing the activity of 1,2,4-triazole. As we increased the bulky group or aromatic group on benzene ring, there was a decrease of activity as in case of compound l.
- Siddiqui, Anees A.,Ahamad, Syed Rizwan,Mir, Mohammed Shehroz,Hussain, Syed Akhtar,Raish, Mohammed,Kaur, Ravindra
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experimental part
p. 223 - 228
(2009/04/04)
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- A simple and efficient synthesis of 4-mercapto-6-phenylpyridazin-3(2h)-ones
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A simple and efficient synthesis of the novel 4-mercapto-6-phenylpyridazin- 3(2H)-ones from the reaction of 6-phenyl-4,5-dihydropyridazin-3(2H)-ones with excess thionyl chloride under mild conditions, is described.
- Tsolomiti, Georgia,Tsolomiti, Kyriaki,Tsolomitis, Athanase
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p. 161 - 164
(2008/02/12)
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- Microwave assisted synthesis of 4,6-diarylpyridazin-3(2H)-ones in solid state
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Microwave assisted synthesis of dihydropyridazin-3(2H)-ones and the subsequent dehydrogenation using selenium dioxide are described.
- Meenakshi,Ramamoorthy,Muthusubramanian,Sivasubramanian
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p. 645 - 651
(2007/10/03)
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- Syntheses and antiinflammatory activity of some 6-aryl-2,3,4,5-tetrahydro-3-pyridazinones
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6-Aryl-2, 3, 4, 5-tetrahydro-3-pyridazinones (2c-22c) are obtained by dehydrocyclisation of various hydrazides formed by the reaction of appropriate methyl β-aroylpropionate and hydrazine hydrate in the presence of anhydrous sodium acetate. They show promising antiinflammatory activity during their evaluation by carrageenin induced paw edema test in rats.
- Khan,Siddiqui
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p. 614 - 619
(2007/10/03)
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- Endothelin receptor antagonists
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This invention relates to pyridizinone derivatives of formula I STR1 wherein the various substituents are defined in the specification, and salts thereof, which have useful pharmacological properties, in particular endothelin receptor-antagonistic properties. The compounds are thus useful for the treatment of illnesses associated with endothelin activities, such as hypertension, cardiac insufficiency, coronary heart disease, renal, cerebral and myocardial ischaemia, renal insufficiency, cerebral infarct, subarachnoid haemorrhage, arteriosclerosis pulmonary high blood pressure, inflammations, asthma, prostate hyperplasia, endotoxic shock and in complications after the administration of immunosuppressants which produce renal vasoconstriction.
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- Synthesis and pharmacology of 3-aryl-5,6-dihydro-6-oxo-1(4H)-pyridazineacetic acid derivatives
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The title compounds were prepared by alkylation of 6-aryl-4,5-dihydro-3(2H)-pyridazinones with esters of α-bromoacetic acid. Hydrolysis of these esters afforded the corresponding carboxylic acids which were coupled with various amines yielding 6-oxo-1(4H)
- Kane,Huber,Miller,Kehne
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p. 249 - 251
(2007/10/02)
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- QUANTITATIVE DETERMINATION OF THE ELECTRONIC EFFECTS OF 3- AND 4-PYRIDAZINYL GROUPS FROM NMR SPECTRAL DATA FOR ISOMERIC AMINOPHENYL- AND PHENYLPYRIDAZINES
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The previously unknown aminophenylpyridazines were synthesized.The inductive and resonance constants of 3- and 4-pyridazinyl groups were calculated on the basis of 1H and 13C NMR spectral data for isomeric aminophenyl- and phenylpyridazines in dimethyl sulfoxide (DMSO).
- Shkurko, O. P.,Kuznetsov, S. A.,Denisov, A. Yu.,Mamaev, V. P.
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p. 763 - 770
(2007/10/02)
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- Substituted 6-phenyl-3(2H)-pyridazinones useful as cardiotonic agents
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Substituted 6-phenyl-3(2H)-pyridazinone compounds are useful as cardiotonic agents. Said compounds cause a significant increase in myocardial contractility in the anesthetized dog. Said compounds are produced by reacting substituted γ-oxobenzenebutanoic acids with suitably substituted hydrazines to provide 6-phenyl-4,5-dihydro-3(2H)-pyridazinones which are dehydrogenated to the desired product. The intermediate 6-phenyl-4,5-dihydro-3(2H)-pyridazinones are themselves useful as cardiotonic agents.
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- Reactions of some Δβ,γ-Butenolides Having no Exocyclic Double bonds
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Ring-opening of γ-aryl-Δβ,γ-butenolides (I) takes place in a different manner compared to those having an exocyclic double bond at the α-position.I react with hydrazine hydrate in cold or boiling ethanol to give 6-aryl-4,5-dihydropyridazine-3(2
- Hashem, A. I.,Shaban, M. E.,El-Kafrawy, A. F.
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p. 763 - 764
(2007/10/02)
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- Method of treating asthma
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A method of treating asthma in a warm-blooded animal using the compound 6-phenyl-1,2,4-triazolo[4,3-b]pyridazin-3(2H)-one.
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