Day: November 21, 2022

Bartolowits, Matthew D. published the artcileDiscovery of inhibitors for proliferating cell nuclear antigen using a computational-based linked-multiple-fragment screen, Computed Properties of 167015-84-1, the publication is ACS Omega (2019), 4(12), 15181-15196, database is CAplus and MEDLINE.

Proliferating cell nuclear antigen (PCNA) is a central factor in DNA replication and repair pathways that plays an essential role in genome stability. The functional roles of PCNA are mediated through an extensive list of protein-protein interactions, each of which transmits specific information in protein assemblies. The flexibility at the PCNA-protein interaction interfaces offers opportunities for the discovery of functionally selective inhibitors of DNA repair pathways. Current fragment-based drug design methodologies can be limited by the flexibility of protein interfaces. These factors motivated an approach to defining compounds that could leverage previously identified subpockets on PCNA that are suitable for fragment-binding sites. Methodologies for screening multiple connected fragment-binding events in distinct subpockets are deployed to improve the selection of fragment combinations. A flexible backbone based on N-alkyl-glycine amides offers a scaffold to combinatorically link multiple fragments for in silico screening libraries that explore the diversity of subpockets at protein interfaces. This approach was applied to discover new potential inhibitors of DNA replication and repair that target PCNA in a multiprotein recognition site. The screens of the libraries were designed to computationally filter ligands based upon the fragments and positions to <1%, which were synthesized and tested for direct binding to PCNA. Mol. dynamics simulations also revealed distinct features of these novel mols. that block key PCNA-protein interactions. Furthermore, a Bayesian classifier predicted 15 of the 16 new inhibitors to be modulators of protein-protein interactions, demonstrating the method’s utility as an effective screening filter. The cellular activities of example ligands with similar affinity for PCNA demonstrate unique properties for novel selective synergy with therapeutic DNA-damaging agents in drug-resistant contexts.

ACS Omega 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, Computed Properties of 167015-84-1.

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

Zhang, Jian published the artcileCooperative N-heterocyclic Carbene and Iridium Catalysis Enables Stereoselective and Regiodivergent [3 + 2] and [3 + 3] Annulation Reactions, Recommanded Product: 5-Fluoro-1H-indole-2-carbaldehyde, the publication is ACS Catalysis (2021), 11(7), 3810-3821, database is CAplus.

A cooperative N-heterocyclic carbene (NHC)/iridium catalysis has been developed to achieve highly stereoselective and regiodivergent [3 + 2] and [3 + 3] annulation reactions of 2-indolyl allyl carbonates I (R = H, Me; R¹ = H, OMe, Me, F, Cl; R¹ = H, OMe, Cl) with enals R³CH=CHCHO (R¹ = Ph, hexyl, 4-chlorophenyl, furan-2-yl, etc.). The use of the NHC catalyst has introduced switchable homoenolate and enolate intermediates from the common enal precursor via a simple adjustment of reaction conditions in a predictable manner. This protocol furnishes two types of biol. important products, pyrrolo[1,2-a]indoles II and pyridine[1,2-a]indoles III, with high diastereo- and enantioselectivities (up to >20:1 dr and >99% ee). Notably, all four stereoisomers of these products with two vicinal stereocenters could be afforded through permutations of the enantiomers of the two chiral catalysts. Mechanistic investigations and further computational d. functional theory calculations give an explanation of the origin of the regioselectivity. In addition, the NHC-enolate intermediate generated from formylcyclopropanes IV (R⁴ = Ph, tert-Bu, naphthalen-2-yl, etc.) was also compatible in this cooperative catalytic system and thus the arsenal of optically pure pyrrolo[1,2-a]indole products V was enriched.

ACS Catalysis 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 C18H12FN, Recommanded Product: 5-Fluoro-1H-indole-2-carbaldehyde.

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

Zhang, Huairong published the artcileIdentification of differentially expressed kinase and screening potential anticancer drugs in papillary thyroid carcinoma, Name: SU6656, the publication is Disease Markers (2016), 2832980/1-2832980/9, database is CAplus and MEDLINE.

We aim to identify protein kinases involved in the pathophysiol. of papillary thyroid carcinoma (PTC) in order to provide potential therapeutic targets for kinase inhibitors and unfold possible mol. mechanisms. The gene expression profile of GSE27155 was analyzed to identify differentially expressed genes and mapped onto human protein kinases database. Correlation of kinases with PTC was addressed by systematic literature search, GO and KEGG pathway anal. The functional enrichment anal. indicated that “mitogen-activated protein kinases pathway” expression was extremely enriched, followed by “neurotrophin signaling pathway,” “focal adhesion,” and “GnRH signaling pathway.”. MAPK, SRC, PDGFRa, ErbB, and EGFR were significantly regulated to correct these pathways. Kinases investigated by the literature on carcinoma were considered to be potential novel mol. therapeutic target in PTC and application of corresponding kinase inhibitors could be possible therapeutic tool. SRC,MAPK, and EGFR were the most important differentially expressed kinases in PTC. Combined inhibitors may have high efficacy in PTC treatment by targeting these kinases.

Disease Markers 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 C20H21ClN4O4, Name: SU6656.

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

Tamm, Christoffer published the artcileDifferential effects on cell motility, embryonic stem cell self-renewal and senescence by diverse Src kinase family inhibitors, HPLC of Formula: 330161-87-0, the publication is Experimental Cell Research (2012), 318(4), 336-349, database is CAplus and MEDLINE.

The Src family of non-receptor tyrosine kinases (SFKs) has been shown to play an intricate role in embryonic stem (ES) cell maintenance. In the present study we have focused on the underlying mol. mechanisms responsible for the vastly different effects induced by various commonly used SFK inhibitors. We show that several diverse cell types, including fibroblasts completely lacking SFKs, cannot undergo mitosis in response to SU6656 and that this is caused by an unselective inhibition of Aurora kinases. In contrast, PP2 and PD173952 block motility immediately upon exposure and forces cells to grow in dense colonies. The subsequent halt in proliferation of fibroblast and epithelial cells in the center of the colonies approx. 24 h post-treatment appears to be caused by cell-to-cell contact inhibition rather than a direct effect of SFK kinase inhibition. Interestingly, in addition to generating more homogenous and dense ES cell cultures, without any diverse effect on proliferation, PP2 and PD173652 also promote ES cell self-renewal by reducing the small amount of spontaneous differentiation typically observed under standard ES cell culture conditions. These effects could not be mirrored by the use of Gleevec, a potent inhibitor of c-Abl and PDGFR kinases that are also inhibited by PP2.

Experimental Cell Research 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 C7H7IN2O, HPLC of Formula: 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

Nemoto, Tetsuhiro published the artcilePd-catalyzed asymmetric allylic amination of Morita-Baylis-Hillman adduct derivatives using chiral diaminophosphine oxides: DIAPHOXs, SDS of cas: 167015-84-1, the publication is Organic Letters (2007), 9(5), 927-930, database is CAplus and MEDLINE.

Asym. allylic amination of allylic carbonates prepared from racemic Morita-Baylis-Hillman adducts proceeded in the presence of Pd catalyst, chiral diaminophosphine oxide (DIAPHOX), and BSA, affording the corresponding chiral aza-Morita-Baylis-Hillman adduct derivatives in excellent yield with up to 99% ee. The cyclic reaction products could be converted into various synthetically useful compounds such as chiral cyclic β-amino acids.

Organic 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 C15H20N2O2, SDS of cas: 167015-84-1.

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

Takeuchi, Yoshinori published the artcileScreening of therapeutic targets for canine mast cell tumors from a variety of kinase molecules, Quality Control of 330161-87-0, the publication is Journal of Veterinary Medical Science (2011), 73(10), 1295-1302, database is CAplus and MEDLINE.

Options of systemic treatment for canine MCT have been still limited and most canine cases with MCTs eventually undergo relapses even after achievement of a remission. Thus addnl. therapies are required to establish for the tumor. To identify the novel candidate therapeutic targets for canine MCT, the mRNA expression and phosphorylation statuses of several receptor or non-receptor kinases as well as the inhibitory effect of 95 specific inhibitors on the growth were assessed in three canine MCT cell lines (HRMC, VIMC1 and CMMC1). Among the 14 targets, the mRNAs of 11, 7 and 7 kinases were amplified in HRMC, VIMC1 and CMMC1, resp. The mRNAs of VEGFR3, PDGFRα, SRC, YES, LCK and FYN were detected in all cell lines. The phosphorylation of 12, 8 and 7 kinases was observed by using specific antibody arrays in HRMC, VIMC1 and CMMC1, resp. DTK, EPHB6, AMPKα1, CREB, STAT5a and STAT5b were phosphorylated in all cell lines. The 10, 9 and 17 inhibitors exhibited the biol. activity against the growth of HRMC, VIMC1 and CMMC1, resp. Only three inhibitors such as SB218078 (for Chk1), PDGF RTK inhibitor IV (for PDGFR) and radicicol (for Hsp90) suppressed the growth of all three cell lines. The present study indicated that several kinases, such as Chk1, PDGFR and Hsp90, could be used as therapeutic targets in the treatment for canine MCT. Further studies and clin. trials are warranted to apply the inhibitors for the treatment of the tumor.

Journal of Veterinary Medical Science 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 C38H74Cl2N2O4, Quality Control 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

Takadera, Tsuneo published the artcileApoptosis Induced by Src-Family Tyrosine Kinase Inhibitors in Cultured Rat Cortical Cells, Recommanded Product: SU6656, the publication is Neurotoxicity Research (2012), 21(3), 309-316, database is CAplus and MEDLINE.

In the central nervous system, members of the Src family of tyrosine kinases (SFKs) are widely expressed and are abundant in neurons. The purpose of this study is to examine whether glycogen synthase-3 (GSK-3) is involved in SFK inhibitor-induced apoptosis. PP2 and SU6656, SFK inhibitors, increased apoptotic cell death with morphol. changes that were characterized by cell shrinkage, chromatin condensation, or nuclear fragmentation. Moreover, both activation of caspase-9 and caspase-3 were accompanied by the cell death. GSK-3 inhibitors, such as alsterpaullone and SB216763, prevented the PP2-induced apoptosis. In addition, insulin-like growth factor-I prevented the PP2-induced cell death and PP2 inhibited phosphorylation of focal adhesion kinase (FAK). Phosphorylation of FAK on Tyr 576 by Src activates FAK. These results suggest that inhibition of SFK induces apoptosis possibly via blocking of FAK/phosphatidylinositol-3 kinase/Akt signaling pathway and activation of GSK-3 is involved in the cell death in rat cortical neurons.

Neurotoxicity Research 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 C12H9N3O4, Recommanded Product: SU6656.

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

Lou, Sha published the artcilePalladium/Tris(tert-butyl)phosphine-Catalyzed Suzuki Cross- Couplings in the Presence of Water, COA of Formula: C15H14BNO4S, the publication is Advanced Synthesis & Catalysis (2010), 352(11+12), 2081-2084, database is CAplus and MEDLINE.

The use of dipalladiumtris(dibenzylideneacetone)/tris(tert-butyl)phosphonium tetrafluoroborate/potassium fluoride dihydrate [Pd₂(dba)₃/[HP(t-Bu)₃]BF₄/KF·2 H₂O] as a mild, robust, and user-friendly method for the efficient Suzuki cross-coupling of a diverse array of aryl and heteroaryl halides with aryl- and heteroarylboronic acids is demonstrated.

Advanced Synthesis & Catalysis published new progress about 149108-61-2. 149108-61-2 belongs to indole-building-block, auxiliary class Indole,Boronic acid and ester,Sulfamide,Benzene,Boronic Acids,Boronic Acids,Boronic acid and ester,, name is (1-tosyl-1H-Indol-3-yl)boronic acid, and the molecular formula is C15H14BNO4S, COA of Formula: C15H14BNO4S.

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

Rae, James published the artcileSynthesis of Axially Chiral C-N Scaffolds via Asymmetric Coupling with Enantiopure Sulfinyl Iodanes, Recommanded Product: 5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)indoline, the publication is ACS Catalysis (2018), 8(4), 2805-2809, database is CAplus.

Axially chiral C-N compounds are an emerging but scarcely investigated class of stereogenic mols. with potential applications as biol. active scaffolds and chiral ligands. The synthesis of these compounds is extremely challenging, and in particular, no metal-catalyzed asym., intermol. C-N coupling has been previously reported. Herein we disclose an intermol. atropselective C-N coupling, occurring with excellent stereoselectivity. This Cu-catalyzed transformation is based on the use of highly active coupling partners (i.e., chiral iodanes bearing a very cheap and traceless sulfoxide auxiliary). Use of such original ortho-sulfoxide iodanes enables this unprecedented coupling to occur at room temperature, guaranteeing high atropselectivity and atropselectivity of the coupling products under reaction conditions. Because of extensive possible postmodifications of the optically pure products, a panel of C-N axially chiral scaffolds can now be accessed.

ACS Catalysis published new progress about 1062174-44-0. 1062174-44-0 belongs to indole-building-block, auxiliary class Indoline,Boronic acid and ester,Indoline,Boronate Esters,Boronic Acids,Boronic acid and ester, name is 5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)indoline, and the molecular formula is C14H20BNO2, Recommanded Product: 5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)indoline.

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

Hoffman, A. published the artcileThe structure and synthesis of psilocybin, Name: Ethyl 7-methoxy-1H-indole-2-carboxylate, the publication is Experientia (1958), 397-9, database is CAplus.

Psilocybin, the psychotropic active principle from Psilocybe mexicana, was found to be the H₃PO₄ ester of 4-hydroxydimethyltryptamine (I). Hydrolysis of I gave 4-hydroxydimethyltryptamine which was synthesized from 4-benzyloxyindole by the oxalyl chloride method (Speeter, et al., C.A. 49, 15852f).

Experientia 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, Name: Ethyl 7-methoxy-1H-indole-2-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