The Davis-Beirut Reaction: A Novel Entry into 2H-indazoles and Indazolones. Recent Biological Activity of Indazoles

Haddadin, Makhluf J.; Conrad, Wayne E.; Kurth, Mark J.

doi:10.2174/138955712802762059

Cited by 73 publications

(33 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The utility of 2H-indazoles as pharmacophore in drug discovery has been exemplified in several recent publications [3][4][5][6] , a substantial research work around the globe enabling the synthesis of such motifs [7][8][9][10] . The planar indazole containing two nitrogen atoms in ring can be functionalized with high selectivity by varying length of side chain and functionalizing at different positions will yield enormous number of indazole derivatives, providing new spectrum of molecules having with therapeutic properties.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Study of 3-Methyl-N-[Arylylmethylene]-1h-Indazol-5-Amines From 2-Hydroxy-4-Amino Acetophenone and Their Anti-Microbial Activity

Sujatha¹,

Rao²,

Khader³

et al. 2020

Int. Res. J. Pharm.

View full text Add to dashboard Cite

Indazole is one of the most important scaffolds in heterocyclic chemistry and drug design and discovery. It is rarely found in nature but widely found in diverse pharmacologically active substances. Indazoles are versatile building-block for lead generation, the indazole core is an active pharmacophore and used in medicinal chemistry and drug discovery research. A number of drugs with indazole core are in the market, In the recent years, many indazole derivatives have been synthesized and subjected to varied biological activities. Here indazoles are prepared from 2-hydroxy-4-amino acetophenone, the free amino group is preprotected and reacted with hydrazine hydrate at elevated temperature thus obtained indazoles are deprotected and hydrazone derivatives were prepared, the newly synthesized indazole derivatives were screened for antibacterial and antifungal activity.

show abstract

Section: Introductionmentioning

confidence: 99%

Synthesis and Study of 3-Methyl-N-[Arylylmethylene]-1h-Indazol-5-Amines From 2-Hydroxy-4-Amino Acetophenone and Their Anti-Microbial Activity

Sujatha¹,

Rao²,

Khader³

et al. 2020

Int. Res. J. Pharm.

View full text Add to dashboard Cite

show abstract

“…10 Indazole, usually referred to as 1 H -indazole, exists in three tautomeric forms (Chart 1). The 1 H -indazole is the dominant tautomer in the gas phase and aqueous solution, 11, 12 as well as in metal complexes, however, some substituted organic 2 H -indazoles are known 13 as well as rare, inorganic examples such as an organoruthenium(II) complex with 2-methyl-indazole, 14 and the osmium(IV) complexes trans -[Os IV Cl 4 (κN1-2 H -ind) 2 ], 15 and (H 2 ind)[Os IV Cl 5 (κN1-2 H -ind)]. 16 The synthesis of the latter complex along with (H 2 ind)[Os IV Cl 5 (κN2-1 H -ind)] made an estimation of the effect of indazole tautomer identity on the antiproliferative activity of osmium(IV) complexes in different human cancer cell lines possible.…”

Section: Introductionmentioning

confidence: 99%

cis-Tetrachlorido-bis(indazole)osmium(iv) and its osmium(iii) analogues: paving the way towards the cis-isomer of the ruthenium anticancer drugs KP1019 and/or NKP1339

et al. 2017

View full text Add to dashboard Cite

The relationship between cis-trans isomerism and anticancer activity has been mainly addressed for square-planar metal complexes, in particular, for platinum(II), e.g., cis- and trans-[PtCl2(NH3)2], and a number of related compounds, of which, however, only cis-counterparts are in clinical use today. For octahedral metal complexes, this effect of geometrical isomerism on anticancer activity has not been investigated systematically, mainly because the relevant isomers are still unavailable. An example of such an octahedral complex is trans-[RuCl4(Hind)2]−, which is in clinical trials now as its indazolium (KP1019) or sodium salt (NKP1339), but the corresponding cis-isomers remain inaccessible. We report the synthesis of Na[cis-OsIIICl4(κN2-1H-ind)2] (Na[1]) to show that cis-isomer of NKP1339 can in principle be prepared as well. The procedure involves heating (H2ind)[OsIVCl5(κN1-2H-ind)] in a high boiling point organic solvent resulting in an Anderson rearrangement with formation of cis-[OsIVCl4(κN2-1H-ind)2] ([1]) in high yield. The transformation is accompanied by an indazole coordination mode switch from κN1 to κN2 and stabilization of the 1H-indazole tautomer. Fully reversible spectroelectrochemical reduction of [1] in acetonitrile at 0.46 V vs NHE is accompanied by a change in electronic absorption bands indicating formation of cis-[OsIIICl4(κN2-1H-ind)2]− ([1]−). Chemical reduction of [1] in methanol with NaBH4 followed by addition of nBu4NCl afforded the osmium(III) complex nBu4N[cis-OsIIICl4(κN2-1H-ind)2] (nBu4N[1]). Metathesis reaction of nBu4N[1] with an ion exchange resin led to isolation of the water-soluble salt Na[1]. The X-ray diffraction crystal structure of [1]·Me2CO was determined and compared with that of trans-[OsIVCl4(κN2-1H-ind)]·2Me2SO (2·2Me2SO), also prepared in this work. EPR spectroscopy was performed on the OsIII complexes and the results analyzed by ligand-field and quantum chemical theories. We furthermore assayed effects of [1] and Na[1] on cell viability and proliferation in comparison to trans-[OsIVCl4(κN1-2H-ind)] [3] and cisplatin and found a strong reduction of cell viability at concentrations between 30 and 300 µM in different cancer cell lines (HT29, H446, 4T1 and HEK293). HT-29 cells are less sensitive to cisplatin than 4T1 cells, but more sensitive to [1] and Na[1], as shown by decreased proliferation and viability as well as an increased late apoptotic/necrotic cell population.

show abstract

“…Over the past decades, a great deal of research interests has been devoted toward the synthesis of heterocyclic compounds because of their remarkable biological activities. Among numerous well‐known heterocycles, indazole derivatives receive an increasingly significant attention in modern drug discovery because the indazole unit is a key structural motif found in various drug substances exhibiting a wide spectrum of biological activities like anti‐platelet , anti‐inflammatory , anti‐cancer , anti‐tumor , anti‐contraceptive , anti‐depressant , anti‐microbial , and anti‐HIV . In addition, indazoles are known as efficient bioisosters of benzimidazoles and indoles .…”

Section: Introductionmentioning

confidence: 99%

“…Because of the unique biological activities of indazole derivatives, a number of synthetic methods were developed to access indazole scaffolds . However, most of the existing approaches have led to the thermodynamically favored 1 H ‐idazoles or a mixture of 1 H ‐indazoles and 2 H ‐indazoles.…”

Section: Introductionmentioning

confidence: 99%

Highly Efficient One‐Pot Three Component Synthesis of 2H‐Indazoles by Consecutive Condensation, C–N and N–N Bond Formations Using Cu/Aminoclay/Reduced Graphene Oxide Nanohybrid

Behrouz

2016

Journal of Heterocyclic Chem

View full text Add to dashboard Cite

A simple and straightforward one‐pot three‐component synthesis of 2H‐indazoles through copper‐catalyzed consecutive condensation, C–N and N–N bond formations of easily accessible starting materials under ligand‐free conditions is described. In this protocol, treatment of substituted 2‐bromobenzaldehydes, structurally diverse amines, and [bmim]N3 in the presence of Cu/aminoclay/reduced graphene oxide nanohybrid (Cu/AC/r‐GO nanohybrid) as an efficient heterogeneous catalyst affords the corresponding 2H‐indazoles in good to excellent yields. The influence of effective parameters on the efficient progress of the reaction was studied. The Cu/AC/r‐GO nanohybrid is a stable and inexpensive catalyst that could be simply prepared, recovered, and reused for several reaction runs with no significant decrease in its reactivity.

show abstract

The Davis-Beirut Reaction: A Novel Entry into 2H-indazoles and Indazolones. Recent Biological Activity of Indazoles

Abstract: A novel, easy method for the syntheses of richly diversified 2H-indazoles and indazolones, called the Davis-Beirut reaction, and other recent 2H-indazole synthetic routes are briefly reviewed. An update on the biological activity of indazoles is also surveyed.

Cited by 73 publications

References 0 publications

Synthesis and Study of 3-Methyl-N-[Arylylmethylene]-1h-Indazol-5-Amines From 2-Hydroxy-4-Amino Acetophenone and Their Anti-Microbial Activity

Synthesis and Study of 3-Methyl-N-[Arylylmethylene]-1h-Indazol-5-Amines From 2-Hydroxy-4-Amino Acetophenone and Their Anti-Microbial Activity

cis-Tetrachlorido-bis(indazole)osmium(iv) and its osmium(iii) analogues: paving the way towards the cis-isomer of the ruthenium anticancer drugs KP1019 and/or NKP1339

Highly Efficient One‐Pot Three Component Synthesis of 2H‐Indazoles by Consecutive Condensation, C–N and N–N Bond Formations Using Cu/Aminoclay/Reduced Graphene Oxide Nanohybrid

Contact Info

Product

Resources

About