Day: November 21, 2022

Velezheva, Valeriya published the artcileSynthesis and antituberculosis activity of indole-pyridine derived hydrazides, hydrazide-hydrazones, and thiosemicarbazones, Category: indole-building-block, the publication is Bioorganic & Medicinal Chemistry Letters (2016), 26(3), 978-985, database is CAplus and MEDLINE.

We describe the design, synthesis, and in vitro antimycobacterial activity of a series of novel simple hybrid hydrazides and hydrazide-hydrazones combining indole and pyridine nuclei. The compounds are derivatives of 1-acetylindoxyl or substituted indole-3-carboxaldehydes tethered via a hydrazine group by simple C-N or double C:N bonds with 3- and 4-pyridines, 1-oxide 3- and 4-pyridine carbohydrazides. The most active of the 15 compounds showed MICs values against an INH-sensitive strain of Mycobacterium tuberculosis H37Rv equal to that of INH (0.05-2 μg/mL). Five compounds demonstrated appreciable activity against the INH-resistant M. tuberculosis CN-40 clin. isolate (MICs: 2-5 μg/mL), providing justification for further in vivo studies.

Bioorganic & Medicinal Chemistry Letters published new progress about 100123-25-9. 100123-25-9 belongs to indole-building-block, auxiliary class Indole,Bromide,Ester,Aldehyde, name is Ethyl 5-bromo-3-formyl-1H-indole-2-carboxylate, and the molecular formula is C15H24O2, Category: indole-building-block.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Knepper, Kerstin published the artcileBartoli Indole Synthesis on Solid Supports, Safety of Methyl 2-methyl-1H-indole-5-carboxylate, the publication is Organic Letters (2003), 5(16), 2829-2832, database is CAplus and MEDLINE.

Bartoli indole synthesis was performed on solid supports. Starting from Merrifield resin, immobilization of five nitrobenzoic acids was performed. Addition of four different alkenyl Grignard reagents and basic cleavage leads to substituted Me indolecarboxylates in excellent purities. Features of this reaction are the stability of halide groups, ester moieties, and tolerance of o,o’-unsubstituted nitro resins. Heck and Sonogashira reactions are also possible with immobilized indoles.

Organic Letters published new progress about 57663-18-0. 57663-18-0 belongs to indole-building-block, auxiliary class Indole,Ester, name is Methyl 2-methyl-1H-indole-5-carboxylate, and the molecular formula is C11H11NO2, Safety of Methyl 2-methyl-1H-indole-5-carboxylate.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Podevin, R. A. published the artcileConcentrative PAH transport by rabbit kidney slices in the absence of metabolic energy, Category: indole-building-block, the publication is American Journal of Physiology (1978), 235(4), F278-F285, database is CAplus and MEDLINE.

Characteristics of p-aminohippurate (PAH) transport in the absence of intracellular metabolism were studied with Na⁺,K⁺-depleted and ouabain-poisoned rabbit kidney cortex slices. The imposition of a NaCl gradient (out to in) resulted in specific stimulation of PAH uptake. PAH accumulated against its concentration gradient when cell Na⁺ concentration [Na⁺] was less than medium [Na⁺]. Conversely, renal cells extruded PAH when cell [Na⁺] exceeded medium [Na⁺]. Membrane potential measured with triphenylmethylphosphonium revealed that conditions which created an interior-pos. membrane potential inhibited the Na⁺-dependent transport of PAH but caused stimulation of the Na⁺-independent component. Characteristics of the Na⁺-dependent PAH transport system in ouabain-poisoned slices were similar to those previously described in metabolically active tissues.

American Journal of Physiology published new progress about 2642-37-7. 2642-37-7 belongs to indole-building-block, auxiliary class Indole,Salt,Sulfonate,Inhibitor,Inhibitor, name is Potassium 1H-indol-3-yl sulfate, and the molecular formula is C8H6KNO4S, Category: indole-building-block.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Shortridge, Matthew D. published the artcileCorrelation between protein function and ligand binding profiles, Quality Control of 2854-32-2, the publication is Journal of Proteome Research (2011), 10(5), 2538-2545, database is CAplus and MEDLINE.

The authors report that proteins with the same function bind the same set of small mols. from a standardized chem. library. This observation led to a quantifiable and rapidly adaptable method for protein functional anal. using exptl. derived ligand binding profiles. Ligand binding is measured using a high-throughput NMR ligand affinity screen with a structurally diverse chem. library. The method was demonstrated using a set of 19 proteins with a range of functions. A statistically significant similarity in ligand binding profiles was only observed between the two functionally identical albumins and between the five functionally similar amylases. This new approach is independent of sequence, structure, or evolutionary information and, therefore, extends the ability to analyze and functionally annotate novel genes.

Journal of Proteome Research published new progress about 2854-32-2. 2854-32-2 belongs to indole-building-block, auxiliary class GPCR/G Protein,Cannabinoid Receptor, name is 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-1-morpholinoethanone, and the molecular formula is C7H6Cl2, Quality Control of 2854-32-2.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Apsel, Beth published the artcileTargeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases, Computed Properties of 1025707-92-9, the publication is Nature Chemical Biology (2008), 4(11), 691-699, database is CAplus and MEDLINE.

The clin. success of multitargeted kinase inhibitors has stimulated efforts to identify promiscuous drugs with optimal selectivity profiles. It remains unclear to what extent such drugs can be rationally designed, particularly for combinations of targets that are structurally divergent. Here we report the systematic discovery of mols. that potently inhibit both tyrosine kinases and phosphatidylinositol-3-OH kinases, two protein families that are among the most intensely pursued cancer drug targets. Through iterative chem. synthesis, X-ray crystallog. and kinome-level biochem. profiling, we identified compounds that inhibit a spectrum of new target combinations in these two families. Crystal structures revealed that the dual selectivity of these mols. is controlled by a hydrophobic pocket conserved in both enzyme classes and accessible through a rotatable bond in the drug skeleton. We show that compound I blocks the proliferation of tumor cells by direct inhibition of oncogenic tyrosine kinases and phosphatidylinositol-3-OH kinases. These mols. demonstrate the feasibility of accessing a chem. space that intersects two families of oncogenes.

Nature Chemical Biology published new progress about 1025707-92-9. 1025707-92-9 belongs to indole-building-block, auxiliary class Indole,Boronic acid and ester,Amide,Aldehyde,Boronate Esters,Boronic Acids,Boronic acid and ester,, name is tert-Butyl 3-formyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylate, and the molecular formula is C20H26BNO5, Computed Properties of 1025707-92-9.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Klegeris, Andis published the artcileReduction of human monocytic cell neurotoxicity and cytokine secretion by ligands of the cannabinoid-type CB2 receptor, Product Details of C23H23ClN2O4, the publication is British Journal of Pharmacology (2003), 139(4), 775-786, database is CAplus and MEDLINE.

Two cannabinoid receptors, CB1 and CB2, have been identified. The CB1 receptor is preferentially expressed in brain, and the CB2 receptor in cells of leukocyte lineage. We identified the mRNA for the CB1 receptor in human neuroblastoma SH-SY5Y cells, and the mRNA and protein for the CB2 receptor in human microglia and THP-1 cells. Δ⁹-And Δ⁸-tetrahydrocannabinol (THC) were toxic when added directly to SH-SY5Y neuroblastoma cells. The toxicity of Δ⁹-THC was inhibited by the CB1 receptor antagonist SR141716A but not by the CB2 receptor antagonist SR144528. The endogenous ligand anandamide was also toxic, and this toxicity was enhanced by inhibitors of its enzymic hydrolysis. The selective CB2 receptor ligands JWH-015 and indomethacin morpholinylamide (BML-190), when added to THP-1 cells before stimulation with lipopolysaccharide (LPS) and IFN-γ, reduced the toxicity of their culture supernatants to SH-SY5Y cells. JWH-015 was more effective against neurotoxicity of human microglia than THP-1 cells. The antineurotoxic activity of JWH-015 was blocked by the selective CB2 receptor antagonist SR144528, but not by the CB1 receptor antagonist SR141716A. This activity of JWH-015 was synergistic with that of the 5-lipoxygenase (5-LOX) inhibitor REV 5901. Cannabinoids inhibited secretion of IL-1β and tumor necrosis factor-α (TNF-α) by stimulated THP-1 cells, but these effects could not be directly correlated with their antineurotoxic activity. Specific CB2 receptor ligands could be useful anti-inflammatory agents, while avoiding the neurotoxic and psychoactive effects of CB1 receptor ligands such as Δ⁹-THC.

British Journal of Pharmacology published new progress about 2854-32-2. 2854-32-2 belongs to indole-building-block, auxiliary class GPCR/G Protein,Cannabinoid Receptor, name is 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-1-morpholinoethanone, and the molecular formula is C23H23ClN2O4, Product Details of C23H23ClN2O4.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Wani, Imtiyaz Ahmad published the artcileTemperature-modulated diastereoselective transformations of 2-vinylindoles to tetrahydrocarbazoles and tetrahydrocycloheptadiindoles, HPLC of Formula: 220943-23-7, the publication is Organic & Biomolecular Chemistry (2018), 16(16), 2910-2922, database is CAplus and MEDLINE.

Direct and expedient access to densely substituted tetrahydrocarbazoles I [R¹ = H, F; R² = H, Me, CH₂CH:CH₂; R³ = OMe, OEt, Ph] and tetrahydrocycloheptadiindoles bearing multiple contiguous stereocenteres II [R¹ = H, F, Cl, Me] were achieved via a two-fold divergent diastereoselective (dr up to >99:1) transformation of 2-vinylindoles. The high-yielding conversions (yield up to 87%) that were amenable for a wide range of substituted 2-vinylindoles proceeded through Lewis acid-catalyzed [4 + 2] and [4 + 3] cyclization-aromatization cascade reactions, resp., involving a heretofore-unprecedented reversal of the polarity (umpolung) of 2-vinylindoles. The two synthetic routes were effortlessly transposable into each other by merely modulating the temperature to furnished the corresponding products in a selective and exclusive fashion. In addition, another novel synthetic route to tetrahydroindolocarbazoles was developed that advances via a formal [4+2] cyclization of 4-vinylindoles involving sequential C3 Michael addition-dearomatization-aromatization cascade reactions. Diastereo- and chemoselective preparation of tetrahydrocarbazoles and tetrahydrocycloheptadiindoles via Fe(OTf)₃ catalyzed tandem cyclization-aromatization of vinylindoles.

Organic & Biomolecular Chemistry published new progress about 220943-23-7. 220943-23-7 belongs to indole-building-block, auxiliary class Indole,Fluoride,Aldehyde, name is 5-Fluoro-1H-indole-2-carbaldehyde, and the molecular formula is C7H4ClIO2, HPLC of Formula: 220943-23-7.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Sidorova, Yulia A. published the artcileA novel small molecule GDNF receptor RET agonist, BT13, promotes neurite growth from sensory neurons in vitro and attenuates experimental neuropathy in the rat, Synthetic Route of 330161-87-0, the publication is Frontiers in Pharmacology (2017), 365/1-365/18, database is CAplus and MEDLINE.

Neuropathic pain caused by nerve damage is a common and severe class of chronic pain. Disease-modifying clin. therapies are needed as current treatments typically provide only symptomatic relief; show varying clin. efficacy; and most have significant adverse effects. One approach is targeting either neurotrophic factors or their receptors that normalize sensory neuron function and stimulate regeneration after nerve damage. Two candidate targets are glial cell line-derived neurotrophic factor (GDNF) and artemin (ARTN), as these GDNF family ligands (GFLs) show efficacy in animal models of neuropathic pain (Boucher et al., 2000; Gardell et al., 2003; Wang et al., 2008, 2014). As these protein ligands have poor drug-like properties and are expensive to produce for clin. use, we screened 18,400 drug-like compounds to develop small mols. that act similarly to GFLs (GDNF mimetics). This screening identified BT13 as a compound that selectively targeted GFL receptor RET to activate downstream signaling cascades. BT13 was similar to NGF and ARTN in selectively promoting neurite outgrowth from the peptidergic class of adult sensory neurons in culture, but was opposite to ARTN in causing neurite elongation without affecting initiation. When administered after spinal nerve ligation in a rat model of neuropathic pain, 20 and 25mg/kg of BT13 decreased mech. hypersensitivity and normalized expression of sensory neuron markers in dorsal root ganglia. In control rats, BT13 had no effect on baseline mech. or thermal sensitivity, motor coordination, or weight gain. Thus, small mol. BT13 selectively activates RET and offers opportunities for developing novel disease-modifying medications to treat neuropathic pain.

Frontiers in Pharmacology published new progress about 330161-87-0. 330161-87-0 belongs to indole-building-block, auxiliary class Protein Tyrosine Kinase/RTK,Src, name is SU6656, and the molecular formula is C8H11NO, Synthetic Route of 330161-87-0.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Gannon, Walter F. published the artcileFischer indole cyclization of several ortho-substituted phenylhydrazones, Related Products of indole-building-block, the publication is Journal of Organic Chemistry (1969), 34(10), 3002-6, database is CAplus.

Fischer indole cyclization of Et pyruvate o-methoxyphenylhydrazone in ethanolic HCl gave 2-carbethoxy-6-chloroindole (I) as the main product. Minor products included 2-carbethoxy-3-chloroindole, the expected 2-carbethoxy-7-methoxyindole and several indolic dimers. Similarly, Et pyruvate o-benzyloxyphenylhydrazone gave I. Cyclization of cyclohexanone o-methoxyphenylhydrazone in dilute H2SO4 yielded 8-methoxy-1,2,3,-4-tetrahydrocarbazole (II) as the major product. The only isolated by-product, previously reported to be 12-methoxy-1,2,3,4-tetrahydroisocarbazole, had a dimeric structure. When the reaction was run in ethanolic HCl, the dimer hydrochloride became the main product and II is formed in lower yield. The structure of the dimers and the reaction mechanism are discussed.

Journal of Organic Chemistry published new progress about 20538-12-9. 20538-12-9 belongs to indole-building-block, auxiliary class Indole,Ester,Ether, name is Ethyl 7-methoxy-1H-indole-2-carboxylate, and the molecular formula is C12H13NO3, Related Products of indole-building-block.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Jacquemard, Ulrich published the artcileMild and selective deprotection of carbamates with Bu₄NF, Application of tert-Butyl 3-(2-aminoethyl)-1H-indole-1-carboxylate, the publication is Tetrahedron (2004), 60(44), 10039-10047, database is CAplus.

A mild method allowing the deprotection of carbamates using TBAF in THF is reported. Reaction was performed on indole, indoline, N-Me aniline, aniline, and tryptamine derivatives The observed selectivity according to the carbamates or the substrates is discussed. A mechanism is also postulated.

Tetrahedron published new progress about 167015-84-1. 167015-84-1 belongs to indole-building-block, auxiliary class Indols, name is tert-Butyl 3-(2-aminoethyl)-1H-indole-1-carboxylate, and the molecular formula is C15H20N2O2, Application of tert-Butyl 3-(2-aminoethyl)-1H-indole-1-carboxylate.

Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles