Structure-Based Design, Synthesis, and Antimicrobial Activity of Indazole-Derived SAH/MTA Nucleosidase Inhibitors

Li, Xiaoming; Chu, Sam; Feher, Victoria A.; Khalili, Mitra; Nie, Zhe; Margosiak, Stephen A.; Nikulin, V. I.; Levin, James C.; Sprankle, Kelly G.; Tedder, Martina E.; Almassy, Robert J.; Appelt, K.; Yager, Kraig M.

doi:10.1021/jm0302039

Cited by 151 publications

(94 citation statements)

References 16 publications

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“…Indazole is a frequently found motif in drug substances with important biological activities such as antimicrobial (Li et al, 2003), anti-inflammatory (Lin et al, 2008) and anticancer effects (Zhu et al, 2007). The crystal structure study of the title compound constitutes a continuation of our previous work on indazole derivatives (Mohamed Abdelahi et al, 2017;El Brahmi et al, 2012).…”

Section: Structure Descriptionmentioning

confidence: 83%

1-(6-Nitro-1H-indazol-1-yl)ethanone

et al. 2017

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In the title molecule, C 9 H 7 N 3 O 3 , the indazole moiety is essentially planar and the mean plane of the acetyl substituent is twisted by 5.3 (1) from its plane. In the crystal, weak C-HÁ Á ÁO and C-HÁ Á ÁN hydrogen bonds form layers parallel to (102), which are associated through -stacking interactions to form a threedimensional network. The structure was refined as a two-component twin. Structure descriptionThe diverse pharmacological properties exhibited by 1H-indazoles have sparked the emergence of novel methods toward their synthesis. Indazole is a frequently found motif in drug substances with important biological activities such as antimicrobial (Li et al., 2003), anti-inflammatory (Lin et al., 2008) and anticancer effects (Zhu et al., 2007). The crystal structure study of the title compound constitutes a continuation of our previous work on indazole derivatives (Mohamed Abdelahi et al., 2017;El Brahmi et al., 2012).The indazole moiety is planar to within 0.0093 (16) Å for (C6) with an r.m.s. deviation from the mean plane of 0.005 Å . The acetyl group is slightly twisted out of the indazole plane, as indicated by the dihedral angle of 5.3 (1) between it and the N2/C8/C9/O1 plane. This orientation may be due in part to the intramolecular C2-H2Á Á ÁO1 hydrogen bond (Table 1 and Fig. 1).In the crystal, the molecules form dimers through pairwise C7-H7Á Á ÁN1 hydrogen bonds which are linked into sheets parallel to (102) by C4-H4Á Á ÁO1 hydrogen bonds (Table 1 and Fig. 2). The sheets stack along the a-axis direction and are associated through head-to-head -stacking interactions (Fig. 3) with centroidÁ Á Ácentroid distances of 3.892 (1) Å .

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Section: Structure Descriptionmentioning

confidence: 83%

1-(6-Nitro-1H-indazol-1-yl)ethanone

et al. 2017

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“…The catalyst and other solid wastes were removed by filtration. The combined organic layer was dried over anhydrous MgSO 4 and concentrated in vacuo to furnish the products 17 Á 24, which were purified by recrystallization in ethanol. 1 H NMR spectrum, two broad singlets, one at 9.85 ppm due to labile NH proton and another at 11.48 ppm due to OH proton disappeared; 13 1 H NMR spectrum, two broad singlets, one at 9.84 ppm due to labile NH proton and another at 11.57 ppm due to OH proton disappeared; 13 1 H NMR spectrum, two broad singlets, one at 9.92 ppm due to labile NH proton and another at 11.51 ppm due to OH proton disappeared; 13 1H, s, H 3 ), 7.25Á8.80 (15H, m, H arom ), 9.97 (1H, bs, NH); in the D 2 O-exchanged 1 H NMR spectrum, a broad singlet at 9.97 ppm due to labile NH proton disappeared; 13 C NMR (d ppm): 13.8 CH 2 CH 3 at C-1, 35.1 C-5, 43.8 C-6, 59.9 CH 2 CH 3 at C-1, 58.7 C-1, 115.5 C-3, 169.2 C 0O at C-1, 158.7 C-2, 123.1Á128.8 ÁC arom , C-4 carbon may be merged with ÁC arom , 129.5, 132.7, 133.6, 134.3, 141.5, 149.5 ipso carbons.…”

Section: Microwave Methodsmentioning

confidence: 99%

“…A wide range of structurally diverse indazole nuclei have aroused enormous interest in the recent years due to their wide variety of pharmacological activities such as antimicrobial activity (1), inhibitors of protein kinase B/Akt (2), leishmanocidal activity (3), antiprotozoal agents (3), antichagasic activity (3), trypanocidal activity (3), inhibitors of S-adenosylhomocysteine/methylthio adenosine nucleosides (4), inhibition of platelet aggregation (5), and potent activator of the nitric oxide receptor (5). The indazole nucleus is a widely studied biological scaffold that has emerged as a core structural unit of a variety of bioactive molecules (6Á10).…”

Section: Introductionmentioning

confidence: 99%

Activated fly ash-catalyzed synthesis of naphthyl-substituted cyclohexenone carboxylates, indazolonols, and nitro hydrazones in “dry media”

Kanagarajan

Ezhilarasi

Thanusu

et al. 2011

Green Chemistry Letters and Reviews

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“…Studies of the structure and physicochemical properties of the indazole ring have been reviewed (Abbassi et al, 2014;Li et al, 2003;Lee et al, 2001). Indazole is a frequently found motif in drug substances with important biological activities, such as antimicrobial (Patel et al, 1999) and anti-inflammatory activities (Lin et al, 2008), and anticancer effects (Zhu et al, 2007).…”

Section: Structure Descriptionmentioning

confidence: 99%

1-(3-Chloro-6-nitro-1H-indazol-1-yl)ethan-1-one

et al. 2017

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The asymmetric unit of the title compound, C 9 H 6 ClN 3 O 3 , contains one full molecule in a general position and a half molcule sitting on a crystallographic mirror plane. In the crystal, molecules form stacks extending along the b-axis direction through a combination of offset -stacking between indazole units and C-ClÁ Á Á (ring) interactions with the six-membered rings of the same units. Elaboration of the C-ClÁ Á Á (ring) interactions along the a-axis direction forms slabs of molecules parallel to [001]. The stacks are joined by a combination of C-HÁ Á ÁO and C-HÁ Á ÁN hydrogen bonds. Structure descriptionStudies of the structure and physicochemical properties of the indazole ring have been reviewed (Abbassi et al., 2014;Li et al., 2003;Lee et al., 2001). Indazole is a frequently found motif in drug substances with important biological activities, such as antimicrobial (Patel et al., 1999) and anti-inflammatory activities (Lin et al., 2008), and anticancer effects (Zhu et al., 2007). As a continuation of our studies of indazole derivatives (Mohamed Abdelahi et al., 2017a,b,c), we report the synthesis and structure of the title compound (Fig. 1).The asymmetric unit of the title compound consists of one molecule in a general position and a half molecule located on a crystallographic mirror plane at y = 1/4. The indazole portion of the former is planar to within 0.007 (1) Å (C16) and the dihedral angle between its mean plane and the mirror on which the latter lies is 4.82 (3) Å . For the overlay of the two independent molecules, values of 0.0130 and 0.0288 Å are obtained, respectively, for the r.m.s. deviation and the maximum deviation. In the crystal, molecules form stacks extending along the b-axis direction. One element of the stack is a dimer formed by pairwise head-to-tail offset -stacking interactions between the indazole (Table 1 and Fig. 4). As shown in Fig. 3, an R 3 3 (19) graph set is formed by two C-HÁ Á ÁO hydrogen bonds and one ClÁ Á ÁO interaction for the molecule in the general position. A corresponding set is formed with the molecule in the special position.

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Structure-Based Design, Synthesis, and Antimicrobial Activity of Indazole-Derived SAH/MTA Nucleosidase Inhibitors

Cited by 151 publications

References 16 publications

1-(6-Nitro-1H-indazol-1-yl)ethanone

1-(6-Nitro-1H-indazol-1-yl)ethanone

Activated fly ash-catalyzed synthesis of naphthyl-substituted cyclohexenone carboxylates, indazolonols, and nitro hydrazones in “dry media”

1-(3-Chloro-6-nitro-1H-indazol-1-yl)ethan-1-one

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