21443-96-9Relevant articles and documents
Efficient synthesis of 7-substituted or 3,7-disubstituted 1H-indazoles
Cottyn, Betty,Vichard, Dominique,Terrier, Fran?ois,Nioche, Pierre,Raman
, p. 1203 - 1206 (2007)
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. Georg Thieme Verlag Stuttgart.
Synthesis and biological evaluation of indazole-4,7-dione derivatives as novel BRD4 inhibitors
Yoo, Minjin,Yoo, Miyoun,Kim, Ji Eun,Lee, Heung Kyoung,Lee, Chong Ock,Park, Chi Hoon,Jung, Kwan-Young
, p. 46 - 56 (2018)
Bromodomain-containing protein 4 (BRD4) is known to regulate the expression of c-Myc to control the proliferation of cancer cells. Therefore, development of small-molecule inhibitors targeting the bromodomain has been widely studied. However, some clinical trials on BRD4 inhibitors have shown its drawbacks such as toxicity including the loss of organ weight. Here, we report the development of the novel and promising scaffold, 1H-indazol-4,7-dione, as a bromodomain inhibitor and synthesized derivatives for the inhibition of binding of bromodomain to acetylated histone peptide. Through this effort, we obtained 6-chloro-5-((2,6-difluorophenyl)amino)-1H-indazole-4,7-dione (5i), which showed a highly potent activity with a half-maximal inhibitory concentration (IC50) of 60?nM. The in vivo xenograft assay confirmed that the 1H-indazol-4,7-dione compound reduced the tumor size significantly. These results show that the 1H-indazol-4,7-dione scaffold is highly potent against bromodomain.
Synthesis of new α-amino-1H indazolyl-phosphonate derivatives: Crystal structure, Hirshfeld surface analysis and DFT studies
Ihammi, Aziz,Chigr, Mohammed,Ketatni, El Mostafa,Saadi, Mohamed,El Ammari, Lahcen,Rakib, El Mostapha
, (2020)
A new α-amino-1H Indazolyl-phosphonates derivative 3a–e were synthesized and subjected to solid state characterization by single-crystal X-ray diffraction analysis, and to study their NMR and Hirshfeld surface analysis. The P atom exhibits tetrahedral geometry involving two O-ethyl groups, a C atom and a double-bonded O atom. The P–C bond has an approximately staggered conformation, with the aniline and substituted groups in gauche positions with respect to the P[dbnd]O double bond. The molecules are arranged as centrosymmetric or pseudocentrosymmetric dimers connected by two N–H?O[dbnd]P hydrogen bonds and also by C–H … π interaction in the case of structures 3a–e, which are responsible for the formation and stability of the molecular assemblies. Hirshfeld surface analysis (dnorm surface and two-dimensional (2D) fingerprint plots) revealed the nature of intermolecular contacts. The most important contributions for the crystal packing are from H?H, H?C/C?H, O?H/H?O, and H?N/N?H interactions. In addition, frontier molecular orbitals and Molecular Electrostatic Potential map of the compounds was produced by using the optimized structures.
N'-hydroxyindazolecarboximidamide derivatives, optical isomer thereof, or pharmaceutically acceptable salts thereof, and, a anticancer composition containing the same as an active ingredient
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Paragraph 0070; 0073; 0074, (2019/02/16)
A Nandprime;-hydroxyindazolecarboxyimidamide derivative compound, which is a pharmaceutical composition for anticancer medicine according to the present invention, an optical isomer thereof or a pharmaceutically acceptable salt thereof have excellent effect of inhibiting indoleamine 2,3-dioxygenase-1, and thus can be usefully used as an anticancer pharmaceutical composition.COPYRIGHT KIPO 2019
Synthesis and molecular modeling studies of N-Hydroxyindazolecarboximidamides as novel indoleamine 2,3-Dioxygenase 1 (IDO1) inhibitors
Lee, Dong-Ho,Lee, Joo-Youn,Jeong, Jieun,Kim, Miok,Lee, Kyung Won,Jang, Eunseo,Ahn, Sunjoo,Lee, Chang Hoon,Hwang, Jong Yeon
, (2017/12/06)
Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive enzyme that is highly overexpressed in various cancer cells and antigen-presenting cells. It has emerged as an attractive therapeutic target for cancer immunotherapy, which has prompted high interest in the development of small-molecule inhibitors. To discover novel IDO1 inhibitors, we designed and synthesized a series of N-hydroxyindazolecarboximidamides. Among the compounds synthesized, compound 8a inhibited both tryptophan depletion and kynurenine production through the IDO1 enzyme. Molecular docking studies revealed that 8a binds to IDO1 with the same binding mode as the analog, epacadostat (INCB24360). Here, we report the synthesis and biological evaluation of these hydroxyindazolecarboximidamides and present the molecular docking study of 8a with IDO1.
Synthesis, antiproliferative and apoptotic activities of N-(6(4)-indazolyl)-benzenesulfonamide derivatives as potential anticancer agents
Abbassi, Najat,Chicha, Hakima,Rakib, El Mostapha,Hannioui, Abdellah,Alaoui, Mdaghri,Hajjaji, Abdelouahed,Geffken, Detlef,Aiello, Cinzia,Gangemi, Rosaria,Rosano, Camillo,Viale, Maurizio
, p. 240 - 249 (2013/01/15)
Recently, it has been reported that compounds bearing a sulfonamide moiety possess many types of biological activities, including anticancer activity. The present work reports the synthesis and antiproliferative evaluation of some N-(6(4)-indazolyl)benzenesulfonamides and 7-ethoxy-N-(6(4)-indazolyl) benzenesulfonamides. All compounds were evaluated for their in vitro antiproliferative activity against three tumor cell lines: A2780 (human ovarian carcinoma) A549 (human lung adenocarcinoma) and P388 (murine leukemia). The results indicated that sulfonamides 2c, 3c, 6d, 8, 13, 3b and 16 were endowed with a pharmacologically interesting antiproliferative activity with compounds 2c and 3c showing the lower IC50 (from 0.50 ± 0.09 to 1.83 ± 0.52 μM and from 0.58 ± 0.17 to 5.83 ± 1.83 μM, respectively). Moreover, these indazoles were able to trigger apoptosis through the upregulation of the typical apoptosis markers p53 and bax. As regard to the hypothetic targets of these compounds, a preliminary docking analysis showed that all compounds seemed to interact with β-tubulin, in particular compound 3b that showed the lower Ki. The cytofluorimetric analysis of the cell cycle phases indicates that all compounds, when administered at their IC 75, caused a block in the G2/M phase of the cell cycle with the generation of subpopulations of cells with a number of chromosome >4n. When the IC50s were applied we observed a prevalent block in the G0/G1 phase except for compounds 16 and 8 where a partial G2/M block was present with a concomitant decrease of cells in the G0/G1 and S phases of the cell cycle. Altogether these results suggest a possible, but not exclusive, interaction with microtubules.
SUBSTITUTED AROMATIC CARBOXAMIDE AND UREA DERIVATIVES AS VANILLOID RECEPTOR LIGANDS
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Page/Page column 124; 125, (2010/11/18)
The invention relates to substituted aromatic carboxamide and urea derivatives, to processes for the preparation thereof, to pharmaceutical compositions containing these compounds and also to the use of these compounds for preparing pharmaceutical compositions (formula (I)).
Anti-cancer agents and uses thereof
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Page/Page column 26, (2008/12/08)
The present invention is in the area of novel compounds and salts thereof, their syntheses, and their use as anti-cancer agents. The compounds include compounds of Formula I: and solvates, hydrates and pharmaceutically-acceptable salts thereof, wherein A1 is N or CR1; A3 is N or CR3; A5 is N or CR5; R1, R3-R6 and L are defined in the specification; n is 0 or 1; and X is an optionally-substituted aryl group having 6-10 carbons in the ring portion, an optionally-substituted 6-membered heteroaryl group having 1-3 nitrogen atoms in the ring portion, an optionally-substituted 5-membered heteroaryl group having 0-4 nitrogen atoms in the ring portion and optionally having 1 sulfur atom or 1 oxygen atom in the ring portion, or an optionally-substituted heteroaryl group in which a 6-membered ring is fused either to a 5-membered ring or to a 6-membered ring, wherein in each case 1, 2, 3 or 4 ring atoms are heteroatoms independently selected from nitrogen, oxygen and sulfur. They are effective against a broad range of cancers, especially leukemia, prostate, non-small cell lung and colon. They are additionally useful in the treatment of proliferative retinopathies such as diabetic neuropathy and macular degeneration.
ANTI-CANCER AGENTS ANS USES THEREOF
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Page/Page column 65, (2010/11/29)
The present invention is in the area of novel compounds and salts thereof, their syntheses, and their use as anti-cancer agents. The compounds include compounds of Formula (I): and solvates, hydrates and pharmaceutically-acceptable salts thereof, wherein A1 is N or CR1; A3 is N or CR3; A5 is N or CR5; R1, R3 R6 and L are defined in the specification; n is 0 or 1; and X is an optionally-substituted aryl group having 6- 10 carbons in the ring portion, an optionally-substituted 6- membered heteroaryl group having 1- 3 nitrogen atoms in the ring portion, an optionally-substituted 5- membered heteroaryl group having 0- 4 nitrogen atoms in the ring portion and optionally having 1 sulfur atom or 1 oxygen atom in the ring portion, or an optionally-substituted heteroaryl group in which a 6- membered ring is fused either to a 5- membered ring or to a 6- membered ring, wherein in each case 1, 2, 3 or 4 ring atoms are heteroatoms independently selected from nitrogen, oxygen and sulfur. They are effective against a broad range of cancers, especially leukemia, prostate, non-small cell lung and colon. They are additionally useful in the treatment of proliferative retinopathies such as diabetic neuropathy and macular degeneration.
Inhibitory effects of a series of 7-substituted-indazoles toward nitric oxide synthases: Particular potency of 1H-indazole-7-carbonitrile
Cottyn, Betty,Acher, Francine,Ramassamy, Booma,Alvey, Luke,Lepoivre, Michel,Frapart, Yves,Stuehr, Dennis,Mansuy, Daniel,Boucher, Jean-Luc,Vichard, Dominique
, p. 5962 - 5973 (2008/12/23)
A series of new 7-monosubstituted and 3,7-disubstituted indazoles have been prepared and evaluated as inhibitors of nitric oxide synthases (NOS). 1H-Indazole-7-carbonitrile (6) was found equipotent to 7-nitro-1H-indazole (1) and demonstrated preference for constitutive NOS over inducible NOS. By contrast, 1H-indazole-7-carboxamide (8) was slightly less potent but demonstrated a surprising selectivity for the neuronal NOS. Further substitution of 6 by a Br-atom at carbon-3 of the heterocycle enhanced 10-fold the inhibitory effects. Inhibition of NO formation by 6 appeared to be competitive versus both substrate and the cofactor (6R)-5,6,7,8-tetrahydro-l-biopterin (H4B). In close analogies with 1, compound 6 strongly inhibited the NADPH oxidase activity of nNOS and induced a spin state transition of the heme-FeIII. Our results are explained with the help of the X-ray structures that identified key-features for binding of 1 at the active site of NOS.
