Month: November 2022

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

Newar, Rajashree published the artcileMono-Phosphine Metal-Organic Framework-Supported Cobalt Catalyst for Efficient Borylation Reactions, Recommanded Product: 2-Methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, the publication is European Journal of Inorganic Chemistry (2022), 2022(10), e202101019, database is CAplus.

The authors report a metal-organic framework (MOF) supported monoligated phosphine-Co complex, which is an active heterogeneous catalyst for aromatic C-H borylation and alkene hydroboration. The mono(phosphine)-Co catalyst (MOF-P-Co) was prepared by metalation of a porous triarylphosphine-functionalized MOF (MOF-P) with CoCl₂ followed by activation with NaEt₃BH. The MOF catalyst has a broad substrate scope with excellent functional group tolerance to afford arene- and alkyl-boronate esters in excellent yields and selectivity. MOF-P-Co gave a turnover number (TON) of 30,000 and could be recycled and reused at least 13 times in arene C-H borylation. Importantly, the attempt to prepare the homogeneous control (Ph₃P-Co) using PPh₃ was unsuccessful due to the facile disproportionation reactions or intermol. ligand exchanges in the solution In contrast, the site isolation of the active mono(phosphine)-Co species within the MOF affords the robust and coordinatively unsaturated metal complexes, allowing to explore their catalytic properties and the reaction mechanism.

European Journal of Inorganic Chemistry published new progress about 919119-59-8. 919119-59-8 belongs to indole-building-block, auxiliary class Indole,Boronic acid and ester,Boronate Esters,Boronic Acids,Boronic acid and ester, name is 2-Methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, and the molecular formula is C15H20BNO2, Recommanded Product: 2-Methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole.

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

Newar, Rajashree published the artcileSingle-Site Cobalt-Catalyst Ligated with Pyridylimine-Functionalized Metal-Organic Frameworks for Arene and Benzylic Borylation, Quality Control of 919119-59-8, the publication is Inorganic Chemistry (2020), 59(15), 10473-10481, database is CAplus and MEDLINE.

A highly active single-site heterogeneous cobalt-catalyst is reported based on a porous and robust pyridylimine-functionalized metal-organic frameworks (pyrim-MOF) for chemoselective borylation of arene and benzylic C-H bonds. The pyrim-MOF having UiO-68 topol., constructed from zirconium-cluster secondary building units and pyridylimine-functionalized dicarboxylate bridging linkers, was metalated with CoCl₂ followed by treatment of NaEt₃BH to give the cobalt-functionalized MOF-catalyst (pyrim-MOF-Co). Pyrim-MOF-Co has a broad substrate scope, allowing the C-H borylation of halogen-, alkoxy-, alkyl-substituted arenes as well as heterocyclic ring systems using B₂pin₂ or HBpin (pin = pinacolate) as the borylating agent to afford the corresponding arene- or alkyl-boronate esters in good yields. Pyrim-MOF-Co gave a turnover number (TON) of up to 2500 and could be recycled and reused at least 9 times. Pyrim-MOF-Co was also significantly more robust and active than its homogeneous control, highlighting the beneficial effect of active-site isolation within the MOF framework that prevents intermol. decomposition The exptl. and computational studies suggested (pyrim^â€?)Co^I(THF) as the active catalytic species within the MOF, which undergoes a mechanistic pathway of oxidative addition, turnover limiting σ-bond metathesis, followed by reductive elimination to afford the boronate ester. The pyridylimine-functionalized metal-organic framework (pyrim-MOF)-based single-site cobalt-catalyst is efficient for chemoselective borylation of arene and benzylic C-H bonds. The heterogeneous MOF-catalyst is significantly more robust and active than its homogeneous control, highlighting the beneficial effect of active-site isolation within the MOF framework that prevents intermol. decomposition

Inorganic Chemistry published new progress about 919119-59-8. 919119-59-8 belongs to indole-building-block, auxiliary class Indole,Boronic acid and ester,Boronate Esters,Boronic Acids,Boronic acid and ester, name is 2-Methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole, and the molecular formula is C15H20BNO2, Quality Control of 919119-59-8.

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

Uno, Tetsuo published the artcileNew submonomers for poly N-substituted glycines (peptoids), Application of tert-Butyl 3-(2-aminoethyl)-1H-indole-1-carboxylate, the publication is Tetrahedron Letters (1999), 40(8), 1475-1478, database is CAplus.

Five protected submonomers for peptoid synthesis were prepared, i.e., Nⁱⁿ-BOC-tryptamine, O-t-butyltyramine, PMC-guanidino-propylamine, 6-amino-6-deoxy-D-galactopyranose diacetonide, and 5-amino-2,2-dimethyl-1,3-dioxane. The first three mimic natural amino acid side chains, i.e., tryptophan, tyrosine, and arginine, while the last two provide hydrophilic side chains. These submonomers were successfully used for preparation of oligo-peptoids by the submonomer synthesis method.

Tetrahedron Letters 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 C7H16Cl2Si, 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

Bowroju, Suresh Kuarm published the artcileI₂/DMSO-catalyzed one-pot approach for the synthesis of 1,3,4-selenadiazoles, HPLC of Formula: 220943-23-7, the publication is RSC Advances (2021), 11(10), 5724-5728, database is CAplus and MEDLINE.

A three-component cascade reaction for the synthesis of 1,3,4-selenadiazoles and their derivatives from arylaldehydes, hydrazine, and elemental selenium by using mol. iodine wais reported. This strategy was operationally simple, well-suited to a wide range of functional groups, and provided the desired products in moderate to excellent yields. The proposed mechanism predicted that the reaction tolerated a radical process.

RSC Advances 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 C9H6FNO, 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