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    Discovery of a novel 2,4-dimethylquinoline-6-carboxamide M 4 positive allosteric modulator (PAM) chemotype via scaffold hopping
    Bioorganic & Medicinal Chemistry Letters (2017)
    Madeline F. LongJulie L. EngersSichen ChangXiaoyan ZhanRebecca L. Weiner
    Moiety
    Carboxamide
    Allosteric modulator
    Structure–activity relationship
    Citations (20)
    Reactive intermediates. Part XVI. Dihydrobenz[cd]indazoles and attempted routes to benz[cd]indazole
    Journal of the Chemical Society. Perkin transactions I/Journal of the Chemical Society. Perkin transactions. I (1972)
    Steven P. BradburyCharles W. ReesR. C. STORR
    Attempted synthesis of 1,2-dihydrobenz[cd]indazole from dimethyl 1,2-dihydrobenz[cd]indazole-1,2-dicarboxylate yielded only the more stable 1,3- and 1,5-dihydro-forms, (7) and (8), with the indazole rather than the naphthalene nucleus aromatic. These indazoles can be reconverted into NN-disubstituted dihydrobenzindazole derivatives but cannot be oxidised to benz[cd]indazole. Several other unsuccessful attempts to obtain the elusive benz[cd]indazole system are described.
    Indazole
    Citations (7)
    Synthesis, Crystal Structure, and Biological Activity of 3-amino-4-morpholino-N- [2-(trifluoromethoxy)phenyl]-1H-indazole-1-carboxamide_esi
    Journal of Chemical Research (2017)
    Indazole
    Carboxamide
    Morpholino
    Citations (0)
    Triazoles from N-Alkynylheterocycles and Their Coordination to Iridium
    Organometallics (2012)
    Glenn A. BurleyY. BoutadlaDavid L. DaviesKuldip Singh
    N-alkynylheterocycles (benzimidazole and indazole) are converted to triazoles by click chemistry, and the resulting triazoles react with [IrCl2Cp*]2. The benzimidazole-triazole coordinates in a monodentate fashion through the benzimidazole, whereas the indazole-triazole is bidentate through coordination of both heterocycles. Reaction of the benzimidazole-triazole with methyliodide gives a benzimidazolium salt that deprotonates on coordination to afford a rare example of a bidentate NHC–triazole.
    Benzimidazole
    Indazole
    Triazole
    1,2,4-Triazole
    Coordination complex
    1,2,3-Triazole
    Citations (12)
    Design and Synthesis of N-Substituted Indazole-3-Carboxamides as Poly(ADP-ribose)polymerase-1 (PARP-1) Inhibitors†
    Chemical Biology & Drug Design (2011)
    Maulik PatelKashyap PandyaCesar A. Lau‐CamSatyakam SinghMaria A. Pino
    A group of novel N-1-substituted indazole-3-carboxamide derivatives were synthesized and evaluated as inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1). A structure-based design strategy was applied to a weakly active unsubstituted 1H-indazole-3-carboxamide 2, by introducing a three carbon linker between 1H-indazole-3-carboxamide and different heterocycles, and led to compounds 4 [1-(3-(piperidine-1-yl)propyl)-1H-indazole-3-carboxamide, IC(50) =36μm] and 5 [1-(3-(2,3-dioxoindolin-1-yl)propyl)-1H-indazole-3-carboxamide, IC(50) = 6.8μm]. Compound 5 was evaluated in rats for its protective action against diabetes induced by a treatment with streptozotocin, a known diabetogenic agent. In addition to preserving the ability of the pancreas to secrete insulin, compound 5 was also able to attenuate the ensuing hyperglycemic response to a significant extent.
    Indazole
    Carboxamide
    Citations (5)
    Synthesis and Structure–Activity Relationship Studies of Conformationally Flexible Tetrahydroisoquinolinyl Triazole Carboxamide and Triazole Substituted Benzamide Analogues as σ2 Receptor Ligands
    Journal of Medicinal Chemistry (2014)
    Su‐Ping BaiShihong LiJinbin XuXin PengKiran Kumar Solingapuram Sai
    Two novel classes of compounds targeting the sigma-2 (σ2) receptor were synthesized, and their bioactivities to binding σ1 and σ2 receptors were measured. Four novel triazole carboxamide analogues, 24d, 24e, 24f, and 39c, demonstrated high affinity and selectivity for the σ2 receptor. These data suggest (11)C-labeled versions of these compounds may be potential σ2-selective radiotracers for imaging the proliferative status of solid tumors.
    Benzamide
    Carboxamide
    Triazole
    1,2,3-Triazole
    1,2,4-Triazole
    Citations (34)
    Indazole- and Indole-5-carboxamides: Selective and Reversible Monoamine Oxidase B Inhibitors with Subnanomolar Potency
    Journal of Medicinal Chemistry (2014)
    Nikolay TzvetkovSonja HinzPetra KüppersMarcus GastreichChrista E. Müller
    Indazole- and indole-carboxamides were discovered as highly potent, selective, competitive, and reversible inhibitors of monoamine oxidase B (MAO-B). The compounds are easily accessible by standard synthetic procedures with high overall yields. The most potent derivatives were N-(3,4-dichlorophenyl)-1-methyl-1H-indazole-5-carboxamide (38a, PSB-1491, IC50 human MAO-B 0.386 nM, >25000-fold selective versus MAO-A) and N-(3,4-dichlorophenyl)-1H-indole-5-carboxamide (53, PSB-1410, IC50 human MAO-B 0.227 nM, >5700-fold selective versus MAO-A). Replacement of the carboxamide linker with a methanimine spacer leading to (E)-N-(3,4-dichlorophenyl)-1-(1H-indazol-5-yl)methanimine (58) represents a further novel class of highly potent and selective MAO-B inhibitors (IC50 human MAO-B 0.612 nM, >16000-fold selective versus MAO-A). In N-(3,4-difluorophenyl-1H-indazole-5-carboxamide (30, PSB-1434, IC50 human MAO-B 1.59 nM, selectivity versus MAO-A>6000-fold), high potency and selectivity are optimally combined with superior physicochemical properties. Computational docking studies provided insights into the inhibitors' interaction with the enzyme binding site and a rationale for their high potency despite their small molecular size.
    Indazole
    Carboxamide
    IC50
    Docking (animal)
    Linker
    Citations (87)
    Synthesis and anticancer activity of 3-amino-N-phenyl-1H-indazole-1-carboxamide, N-phenyl-3-(phenylureido)-1H-indazole-1-carboxamide and 1-(1H)indazol-3-yl-3-phenylureido derivatives
    Demetrio RaffaBenedetta MaggioStella CascioferroV. RaimondiD Schillaci
    Indazole
    Carboxamide
    Citations (0)
    Linear propargylic alcohol functionality attached to the indazole-7-carboxamide as a JAK1-specific linear probe group
    Bioorganic & Medicinal Chemistry (2013)
    Mi Kyoung KimHeerim ShinSeo Young ChoYouhoon Chong
    Indazole
    Carboxamide
    Structure–activity relationship
    Citations (9)
    Efficient Synthesis of 7-Substituted or 3,7-Disubstituted 1H-Indazoles
    Synlett (2007)
    Dominique VichardBetty CottynFrançois TerrierPierre NiocheC.S. Raman
    This work reports on the synthesis of the novel indazole scaffolds 7-OTf-1H-indazole (trifluoromethanesulfonic acid 1H-­indazol-7-yl ester), 7-iodo-1H-indazole and 3-bromo-7-iodo-1H-indazole. These new compounds are potent building blocks in ­divergent syntheses of indazoles via palladium cross-coupling ­reactions.
    Indazole
    Citations (5)