Search results for "indazole"

showing 10 items of 63 documents

Synthesis of [1,2]oxazolo[5,4-e]indazoles as antitumour agents

2013

Abstract A series of 40 derivatives of the [1,2]oxazolo[5,4-e]indazoles ring system have been prepared with good yields using a versatile and convenient route. Annelation of the [1,2]oxazole ring on the indazole-4-one system was achieved by reaction of the corresponding enaminoketones with hydroxylamine hydrochloride. Derivatives of the title ring system were tested by the National Cancer Institute of Bethesda and one of them (13t) showed growth-inhibitor activity against all the 54 human tumour cell lines generally at low micromolar concentrations.

Annulation2]Oxazolo[5StereochemistryOrganic ChemistryHydroxylamine hydrochlorideAntiproliferative activityRing (chemistry)Hydroxylamine HydrochlorideBiochemistryMedicinal chemistrySettore CHIM/08 - Chimica Farmaceutica[12]Oxazolo[54-e]indazoles Enaminoketones Hydroxylamine hydrochloride Antiproliferative activitychemistry.chemical_compoundEnaminoketoneschemistryDrug Discovery4-e]indazoles[1; 2]Oxazolo[5; 4-e]indazoles; Enaminoketones; Hydroxylamine hydrochloride; Antiproliferative activity[1Oxazole
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Synthesis and antifungal activity of new N-(1-phenyl-4-carbetoxypyrazol-5-yl)-, N-(indazol-3-yl)- and N-(indazol-5-yl)-2-iodobenzamides

2002

N-(1-Phenyl-4-carbetoxypyrazol-5-yl)-, N-(indazol-3-yl)- and N-(indazol-5-yl)-2-iodobenzamides 6, with a Benodanil-like structure, were synthesized by refluxing in acetic acid the corresponding benzotriazinones 5 with potassium iodide for 1 h in order to study the role on the antifungal activity of the N-substitution with an aromatic heterocyclic system on benzamide moiety. Among the tested iododerivatives, compounds 6d,f,g,h possess interesting activities toward some phytopathogenic fungal strains.

AntifungalAntifungal AgentsIndazolesMagnetic Resonance SpectroscopySpectrophotometry Infraredmedicine.drug_classStereochemistryColony Count MicrobialPharmaceutical Sciencechemistry.chemical_elementCarboxamideMicrobial Sensitivity TestsIodineChemical synthesisAcetic acidchemistry.chemical_compoundN-(1-phenyl-4-carbetoxypyrazol-5-yl)-2-iodobenzamides N-(indazol-3-yl)-2-iodobenzamides N-(indazol-3-yl)-2-iodobenzamides antifungal activityDrug DiscoverymedicineMoietyBenzamideChemistryFungiSettore CHIM/08 - Chimica FarmaceuticaBenzamidesPyrazolesIl Farmaco
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Preclinical and clinical evidence of activity of pazopanib in solitary fibrous tumour

2014

Abstract Background To explore the activity of pazopanib in solitary fibrous tumour (SFT). Patients and methods In a preclinical study, we compared the activity of pazopanib, sorafenib, sunitinib, regorafenib, axitinib and bevacizumab in a dedifferentiated-SFT (DSFT) xenotransplanted into Severe Combined Immunodeficiency (SCID) mice. Antiangiogenics were administered at their reported optimal doses when mean tumour volume (TV) was 80 mm3. Drug activity was assessed as TV inhibition percentage (TVI%). From May 2012, six consecutive patients with advanced SFT received pazopanib, on a national name-based programme. In one case sunitinib was administered after pazopanib failure. Results In the …

Chemotherapy; Pazopanib; Sarcoma; Solitary fibrous tumour; Sunitinib; Tyrosine kinase; Administration Oral; Adult; Aged; Angiogenesis Inhibitors; Animals; Antibodies Monoclonal Humanized; Antineoplastic Agents; Bevacizumab; Humans; Imidazoles; Indazoles; Indoles; MAP Kinase Signaling System; Male; Mice SCID; Middle Aged; Neoplasm Transplantation; Niacinamide; Phenylurea Compounds; Pyridines; Pyrimidines; Pyrroles; Receptor Platelet-Derived Growth Factor beta; Solitary Fibrous Tumors; Sulfonamides; Transplantation Heterologous; Vascular Endothelial Growth Factor Receptor-2; Cancer Research; Oncology; Medicine (all)OncologyMaleCancer ResearchIndolesAxitinibPyridinesPyridinemedicine.medical_treatmentSolitary fibrous tumourAdministration OralAngiogenesis InhibitorsMice SCIDPharmacologyPyrroleAntineoplastic Agentchemistry.chemical_compoundMiceSolitary Fibrous TumorChemotherapy; Pazopanib; Sarcoma; Solitary fibrous tumour; Sunitinib; Tyrosine kinase; Cancer Research; Oncology; Medicine (all)Transplantation HeterologouMonoclonalSunitinibHumanizedSulfonamidesHeterologousSunitinibMedicine (all)ImidazolesSarcomaMiddle AgedSorafenibPlatelet-Derived Growth Factor betaAxitinibBevacizumabOncologySolitary Fibrous TumorsAdministrationAngiogenesis InhibitorHumanmedicine.drugReceptorPhenylurea CompoundSorafenibOralAdultNiacinamidemedicine.medical_specialtyIndazolesBevacizumabMAP Kinase Signaling SystemTransplantation HeterologousAntineoplastic AgentsSulfonamideAntibodies Monoclonal HumanizedSCIDAntibodiesReceptor Platelet-Derived Growth Factor betaPazopanibInternal medicineRegorafenibmedicineAnimalsHumansChemotherapyPyrrolesImidazoleTyrosine kinaseAgedChemotherapyTransplantationAnimalbusiness.industryPhenylurea CompoundsPazopanibmedicine.diseaseChemotherapy; Pazopanib; Sarcoma; Solitary fibrous tumour; Sunitinib; Tyrosine kinase; Administration Oral; Adult; Aged; Angiogenesis Inhibitors; Animals; Antibodies Monoclonal Humanized; Antineoplastic Agents; Axitinib; Bevacizumab; Humans; Imidazoles; Indazoles; Indoles; MAP Kinase Signaling System; Male; Mice SCID; Middle Aged; Neoplasm Transplantation; Niacinamide; Phenylurea Compounds; Pyridines; Pyrimidines; Pyrroles; Receptor Platelet-Derived Growth Factor beta; Solitary Fibrous Tumors; Sorafenib; Sulfonamides; Sunitinib; Transplantation Heterologous; Vascular Endothelial Growth Factor Receptor-2Vascular Endothelial Growth Factor Receptor-2IndazolePyrimidinesPyrimidinechemistryIndolebusinessProgressive diseaseNeoplasm Transplantation
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Cycloaddition reactions of 1-tert-butyl-4-vinylpyrazole

1989

1-tert-Butyl-4-vinylpyrazole1 a reacts with dimethyl acetylenedicarboxylate (DMAD), methyl propiolate (MP) and N-phenylmaleimide (NPMI) affording the indazole derivatives2,3, and5 as a result of a Diels-Alder ([4 + 2]) cycloaddition. With diethylazodicarboxylate (DEAZD), tetracyanoethylene (TCNE) and 4-phenyl-1,2,4-triazole-3,5-dione (PTAD) the reaction takes place exclusively through the olefinic substituent and the adducts6,7, and9 were isolated. The alkenylpyrazoles1 b–d reacted withDMAD and N-phenylmaleimide to give polymers.

Dimethyl acetylenedicarboxylateTert butylchemistry.chemical_compoundIndazolechemistryMethyl propiolateDiels alderSubstituentOrganic chemistryGeneral ChemistryTetracyanoethyleneMedicinal chemistryCycloadditionMonatshefte f�r Chemie Chemical Monthly
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ChemInform Abstract: Cycloaddition Reactions of 1-tert.-Butyl-4-vinylpyrazole.

1990

1-tert-Butyl-4-vinylpyrazole1 a reacts with dimethyl acetylenedicarboxylate (DMAD), methyl propiolate (MP) and N-phenylmaleimide (NPMI) affording the indazole derivatives2,3, and5 as a result of a Diels-Alder ([4 + 2]) cycloaddition. With diethylazodicarboxylate (DEAZD), tetracyanoethylene (TCNE) and 4-phenyl-1,2,4-triazole-3,5-dione (PTAD) the reaction takes place exclusively through the olefinic substituent and the adducts6,7, and9 were isolated. The alkenylpyrazoles1 b–d reacted withDMAD and N-phenylmaleimide to give polymers.

Dimethyl acetylenedicarboxylateTert butylchemistry.chemical_compoundIndazolechemistryMethyl propiolateSubstituentGeneral MedicineTetracyanoethyleneMedicinal chemistryCycloadditionChemInform
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Synthesis of 2-anilinobenzimidates, anthranilamides, and 2,3-dihydroquinazolin-4(1H)-ones from N-heterocyclic carbenes of indazole

2015

N-Heterocyclic carbenes of indazole (indazol-3-ylidenes), which are substituted at N1 with aromatics were generated in situ from the corresponding indazolium salts. At 60 °C the indazol-3-ylidenes underwent a ring-opening under N–N bond cleavage to intermediary N-(6-methylenecyclohexa-2,4-dien-1-ylidene)anilines. Trapping of these intermediates by alcohols proved to be a convenient method for the preparation of 2-anilinobenzimidates, which have scarcely been described in the literature. The reaction temperature avoids carbene dimerization, which occurs at −80 °C or rearrangement of the ring-opened intermediate to acridines, which affords 100 °C. Water converted the ring-opened products into…

Indazole010405 organic chemistryCarbene dimerizationbenzamideOrganic Chemistryanthranilic acidFormaldehyde010402 general chemistry01 natural sciencesBiochemistryMedicinal chemistry0104 chemical sciencescarbenechemistry.chemical_compoundReaction temperaturechemistryDrug DiscoveryAnthranilic acidOrganic chemistryBenzamideCarbeneta116indazol-3-ylideneBond cleavagebenzenecarboximidic acidTetrahedron
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Convenient synthesis of pyrrolo[3,4-g]indazole

2013

Abstract The synthesis of a novel class of tetrahydropyrrolo[3,4-g]indazoles is reported, by annelation of the pyrazole ring on the isoindole moiety by means of 5-hydroxymethylene tetrahydroisoindole-4-ones key intermediates, with good regioselectivity. Dihydroderivatives were also obtained by oxidation with DDQ of the corresponding tetrahydropyrrolo[3,4-g]indazoles. The growth inhibitory effect was evaluated at the National Cancer Institute of Bethesda and some derivatives showed modest activity.

IndazoleAnnulationTetrahydropyrrolo[3; 4-g]indazole; Hydroxymethyleneketones; Antiproliferative activity; RegioselectivityStereochemistryTetrahydropyrrolo[3Organic ChemistryRegioselectivity4-g]indazoleGrowth inhibitoryAntiproliferative activityPyrazoleRing (chemistry)Settore CHIM/08 - Chimica FarmaceuticaBiochemistryTetrahydropyrrolo[34-g]indazole Hydroxymethyleneketones Antiproliferative activity Regioselectivitychemistry.chemical_compoundRegioselectivitychemistryHydroxymethyleneketonesDrug DiscoveryMoietyIsoindoleTetrahedron
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Synthesis of Fluorinated Indazoles Through ANRORC-Like Rearrangement of 1,2,4-Oxadiazoles with Hydrazine.

2006

A series of 6-substituted fluorinated indazoles has been obtained through an ANRORC-like rearrangement (Addition of Nucleophile, Ring-Opening and Ring-Closure) of 5-tetrafluorophenyl-1,2,4-oxadiazoles with hydrazine. The initial addition of the bidentate nucleophile to the electrophilic C(5) of the 1,2,4-oxadiazole ring, followed by ring opening and ring closure, leads to the formation of fluorinated indazoles in high yield under mild experimental conditions. Functionalization of the C(6) in the final indazole nucleus was preliminarily achieved through a nucleophilic aromatic substitution on the starting 5-pentafluorophenyl-1,2,4-oxadiazole.

IndazoleDenticityOrganic ChemistryHydrazine124-oxadiazoleGeneral MedicineRing (chemistry)BiochemistryMedicinal chemistrychemistry.chemical_compoundchemistryNucleophileNucleophilic aromatic substitutionYield (chemistry)Drug DiscoveryElectrophileindazoleOrganic chemistryfluorinated heterocycleANRORC-like rearrangementsChemInform
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Synthesis and biological evaluation of new indazole derivatives

2010

New N-methyl and N-ethyl substitutions in the indazole nucleus are reported by reacting 3-(2-aminobenzamido)indazole and the appropriate trimethyl/triethyl orthobenzoate. Single crystal X-ray analysis confirms the N-ethylation position for the 3-(1-ethyl-1H-indazol-3-yl)-2-phenylquinazolin-4(3H)-one derivative 3f. Compounds 11a-d and 3a-d were tested to evaluate their antimicrobial, their antiproliferative activity and their COX inhibitory activities showing scarce or moderately antiproliferative activity and some inhibitory activity against COX-1 and COX-2.

IndazoleStereochemistryOrganic Chemistrybiological activityBiological activityAntimicrobialSettore CHIM/08 - Chimica Farmaceuticalcsh:QD241-441chemistry.chemical_compoundN-methyl/N-ethyl alkylationlcsh:Organic chemistry4(3H)-quinazolinonechemistryindazolecrystallographyBiological evaluationArkivoc
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Synthesis and antiproliferative activity of 3-amino-N-phenyl-1H-indazole-1-carboxamides

2007

Abstract A series of new 3-amino-N-phenyl-1H-indazole-1-carboxamides 10 have been prepared from commercially available phenyl isocyanate precursors 8 and 3-aminoindazole 9. Some of the synthesized compounds were evaluated for their in vitro antineoplastic activity against 60 human cell lines derived from seven clinically isolated cancer types (lung, colon, melanoma, renal, ovarian, brain, and leukemia) according to the NCI standard protocol. The test results indicated that 3-amino-1H-indazole-1-carboxamides 10 were endowed with an interesting antiproliferative activity. The most active compounds of this series, 10d,e, were able to inhibit cell growth of many neoplastic cell lines at concent…

IndazolesAntineoplastic AgentsCrystallography X-RayRetinoblastoma Proteinchemistry.chemical_compoundStructure-Activity RelationshipCell Line TumorNeoplasmsDrug DiscoverymedicineHumansCell ProliferationG0-G1 arrestPharmacologyIndazoleMolecular StructureChemistryCell growthMelanomaOrganic ChemistryCell CycleCancer1H-Indazole-1-carboxamides; Crystallographic study; G0-G1 arrest; pRb1H-Indazole-1-carboxamideGeneral MedicineCell cyclemedicine.diseaseAmidesSettore CHIM/08 - Chimica FarmaceuticaIn vitroCrystallographyc studyLeukemiapRbBiochemistryNeoplastic cell
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