Month: November 2022

Lillich, Felix F. published the artcileStructure-Based Design of Dual Partial Peroxisome Proliferator-Activated Receptor γ Agonists/Soluble Epoxide Hydrolase Inhibitors, COA of Formula: C11H11NO2, the publication is Journal of Medicinal Chemistry (2021), 64(23), 17259-17276, database is CAplus and MEDLINE.

A dual partial PPARγ agonist/sEH inhibitor using a structure-guided approach was designed. Exhaustive structure-activity relationship studies lead to the successful optimization of the designed lead. Crystal structures of one representative compound with both targets revealed potential points for optimization. The optimized compounds exhibited favorable metabolic stability, toxicity, selectivity, and desirable activity in adipocytes and macrophages.

Journal of Medicinal Chemistry 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, COA of Formula: C11H11NO2.

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

Jones, Melissa published the artcileTherapeutic effect of the substrate-selective COX-2 inhibitor IMMA in the animal model of chronic constriction injury, Product Details of C23H23ClN2O4, the publication is Frontiers in Pharmacology (2018), 1481, database is CAplus and MEDLINE.

Enhancement of endocannabinoid signaling has emerged as an attractive strategy for the treatment of pain. In addition to the well-characterized hydrolytic pathways, cyclooxygenase-2 (COX-2) mediated oxygenation is thought to be an alternative route for endocannabinoid metabolism and therefore provides a new avenue for drug intervention. In this study, we examined the therapeutic effect of indomethacin morpholinamide (IMMA), a novel substrate-selective COX-2 inhibitor, in the chronic constriction injury (CCI) mouse model. Treatment with IMMA significantly alleviated hyperalgesia and mech. allodynia demonstrated by increased thermal withdrawal latency in Hargreaves test and tactile thresholds in Von Frey test. Accumulation of astrocytes and microglia in spinal cord dorsal horn and infiltration of macrophages into the dorsal root ganglion and sciatic nerve were reduced by drug treatment. Coadministration of the CB2 receptor antagonist, but not the CB1 receptor antagonist partially reversed the inhibitory effect of IMMA on pain sensitivity and inflammatory infiltrates. IMMA downregulated the mRNA expression of TNF- α and IL-1β and the production of IL-6 and MCP-1 proteins in the ipsilateral sciatic nerve. The enhanced NF- κB DNA binding activity in the CCI mouse dorsal spinal cord was also significantly reduced, suggesting that inactivation of NF- κB contributes to the anti-inflammatory property of IMMA. However, different from the previous reports showing that IMMA can increase endocannabinoids without interfering with arachidonic acid metabolism, treatment with IMMA failed to elevate the endogenous levels of AEA and 2-AG, but significantly reduced the production of prostaglandin E2 (PGE2). Furthermore, the mRNA expression of enzymes involved in PGE2 production, COX-2 and prostaglandin E synthase 2 in the ipsilateral sciatic nerve was also suppressed by IMMA treatment. Taken together, these results suggested that IMMA might exert anti-nociceptive effects through multiple mechanisms which include, but are not limited to, CB2 receptor activation and reduced PGE2 production

Frontiers in 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

Remers, William A. published the artcileSynthesis of indoles from 4-oxo-4,5,6,7-tetrahydroindoles. III. Introduction of substituents by electrophilic substitution, Recommanded Product: 2-Bromo-6,7-dihydro-1H-indol-4(5H)-one, the publication is Journal of Organic Chemistry (1971), 36(9), 1241-7, database is CAplus.

The general method of indole synthesis by way of 4-oxo-4,5,6,7-tetrahydroindoles (I) was extended by a variety of electrophilic substitution reactions, including bromination, nitration, acylation, and formylation. An order of selective substitution was established as follows: C-2 > C-3 > C-5, except in certain Vilsmeier-Haack formylations of 2-substituted compounds. When the pyrrole ring of a I was substituted with a strong electron-withdrawing group, electrophilic substitution was diverted to C-5. Most of the 6,7-dihydroindoles prepared in this investigation could be dehydrogenated to the fully aromatic indoles, but many of the new I were resistant to dehydrogenation. Vilsmeier-Haack formylation of certain I led directly to fully aromatic indoles which had a 4-chloro-5-(dimethylaminomethyl) pattern of substitution.

Journal of Organic Chemistry published new progress about 27784-79-8. 27784-79-8 belongs to indole-building-block, auxiliary class Other Aromatic Heterocyclic,Bromide,Ketone, name is 2-Bromo-6,7-dihydro-1H-indol-4(5H)-one, and the molecular formula is C8H8BrNO, Recommanded Product: 2-Bromo-6,7-dihydro-1H-indol-4(5H)-one.

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, Yan-Yan published the artcileDual-role of PtCl₂ catalysis in the intramolecular cyclization of (hetero)aryl-allenes for the facile construction of substituted 2,3-dihydropyrroles and polyheterocyclic skeletons, Safety of 5-Fluoro-1H-indole-2-carbaldehyde, the publication is Chemical Communications (Cambridge, United Kingdom) (2017), 53(44), 5966-5969, database is CAplus and MEDLINE.

A Pt(II)-catalyzed cyclization of (hetero)aryl-allenes were developed, providing controllable synthesis of substituted 2,3-dihydropyrroles and polyheterocyclic skeletons. Another notable feature of this method was the dual-role of the Pt(II) catalyst: initiation of the migration of the (hetero)arylmethylene group and the subsequent Friedel-Crafts type annulation.

Chemical Communications (Cambridge, United Kingdom) 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 C5H5F3O2, Safety of 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

Murakami, Yasuoki published the artcileA novel method for the debenzylation of protected indole nitrogen, Related Products of indole-building-block, the publication is Synthesis (1984), 738-40, database is CAplus.

The AlCl₃-catalyzed deprotection of indoles I (R = H, OMe, Cl, COMe; R¹ = OEt, Me) gave the resp. II. I (R = 7-Cl, R¹ = OEt) was stirred with AlCl₃ in C₆H₆ 30 min to give 66% II (R = 7-Cl, R¹ = OEt).

Synthesis 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

Murakami, Yasuoki published the artcileFischer indolization of ethyl pyruvate 2-bis(2-methoxyphenyl)hydrazone and new insight into the mechanism of Fischer indolization. Fischer indolization and its related compounds. XXVII., Formula: C12H13NO3, the publication is Chemical & Pharmaceutical Bulletin (1995), 43(8), 1287-93, database is CAplus.

In connection with studies on the direction of cyclization in the Fischer indolization of substituted diphenylhydrazones, the Fischer indolization of Et pyruvate 2-bis(2-methoxyphenyl)hydrazone was carried out. The result showed that cyclization in Fischer indolization of diphenylhydrazone does not always proceed to the electron-richer nucleus, but depends on the conformation of the enehydrazine. Thus, the Fischer indolization should proceed via a [3,3] sigmatropic route, with an electronic effect.

Chemical & Pharmaceutical Bulletin 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, Formula: C12H13NO3.

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

Murakami, Yasuoki published the artcileSynthetic studies of indoles and related compounds. Part 16. Synthesis of linear ethyl 9-methoxy-1H-benz[f]indole-2-carboxylate, Synthetic Route of 20538-12-9, the publication is Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999) (1988), 3005-12, database is CAplus.

The preparation of the title compound (I) is reported. I has different phys. properties from those of the indole previously reported (Goldsmith, E. A. and Lindwall, H. G., 1953) as I. I was prepared via a Friedel-Crafts acylation of Et pyrrole-2-carboxylate with phthalic anhydride and by the room temperature AlCl₃-MeOPh induced debenzylation of N-benzylindoes, e.g., II, that contain a methoxy substituent.

Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999) 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, Synthetic Route of 20538-12-9.

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

Song, Jiahui published the artcileCopper-Catalyzed N-Alkynylation of N-tert-Butoxycarbonyl (BOC)-Protected Indoles, Name: tert-Butyl 5-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylate, the publication is Asian Journal of Organic Chemistry (2013), 2(10), 877-881, database is CAplus.

N-BOC-indole derivatives undergo a copper-catalyzed N-alkynylation with alkynyl bromides after in situ deprotection. Potassium tert-butoxide was used for the deprotection of substrates and as a base during the cross-coupling stage. For substrates that contain a 2-pyridine group or similar group, a phenanthroline ligand was not needed. This serves as an alternative protocol for N-alkynylation of indoles with a broader scope of substrates. The title compounds thus formed included an (ethynyl)indole derivative (I) and related substances. The synthesis of the target compounds was achieved using 3-(2-pyridinyl)-1H-indole-1-carboxylic acid 1,1-dimethylethyl ester, 5-(2-pyridinyl)-1H-indole-1-carboxylic acid 1,1-dimethylethyl ester, 1H-Indole-1,2-dicarboxylic acid 1,2-bis(1,1-dimethylethyl) ester, 4-cyano-1H-indole-1-carboxylic acid 1,1-dimethylethyl ester, etc., as starting materials in a reaction with bromoalkyne derivatives A similar reaction of 1H-benzimidazole-1-carboxylic acid 1,1-dimethylethyl ester gave 1-(2-phenylethynyl)-1H-benzimidazole. A reaction of 1H-pyrrole-1-carboxylic acid 1,1-dimethylethyl ester derivatives gave 1-(2-phenylethynyl)-1H-pyrrole derivatives

Asian Journal of Organic Chemistry published new progress about 1256359-99-5. 1256359-99-5 belongs to indole-building-block, auxiliary class Indole,Boronic acid and ester,Amide,Ether,Boronic Acids,Boronate Esters, name is tert-Butyl 5-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-1-carboxylate, and the molecular formula is C38H74Cl2N2O4, Name: tert-Butyl 5-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-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

Chen, Hu published the artcileA copper-catalyzed aerobic domino process for the synthesis of isoindolin-1-ylidene derivatives, Synthetic Route of 167015-84-1, the publication is Tetrahedron (2015), 71(22), 3632-3636, database is CAplus.

A convenient and efficient copper-catalyzed aerobic cascade reaction was developed for the synthesis of the pharmacol. relevant isoindolin-1-ylidene scaffold. Various ortho-formyl cinnamates could react smoothly with different amines in the presence of a com. available copper catalyst under mild aerobic conditions. Isoindolin-1-ylidene derivatives were assembled in one pot in moderate to good yields. This method features amine annulation and double dehydrogenation, representing high at. efficiency. Its product could be further converted to the privileged isoindolinone pharmacophore.

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, Synthetic Route 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

Shen, Aijun published the artcilec-Myc Alterations Confer Therapeutic Response and Acquired Resistance to c-Met Inhibitors in MET-Addicted Cancers, Safety of SU6656, the publication is Cancer Research (2015), 75(21), 4548-4559, database is CAplus and MEDLINE.

Use of kinase inhibitors in cancer therapy leads invariably to acquired resistance stemming from kinase reprogramming. To overcome the dynamic nature of kinase adaptation, we asked whether a signal-integrating downstream effector might exist that provides a more applicable therapeutic target. In this study, we reported that the transcriptional factor c-Myc functions as a downstream effector to dictate the therapeutic response to c-Met inhibitors in c-Met-addicted cancer and derived resistance. Dissociation of c-Myc from c-Met control, likely overtaken by a variety of reprogrammed kinases, led to acquisition of drug resistance. Notably, c-Myc blockade by RNA interference or pharmacol. inhibition circumvented the acquired resistance to c-Met inhibition. Combining c-Myc blockade and c-Met inhibition in MET-amplified patient-derived xenograft mouse models heightened therapeutic activity. Our findings offer a preclin. proof of concept for the application of c-Myc-blocking agents as a tactic to thwart resistance to kinase inhibitors. Cancer Res; 75(21); 4548-59. ©2015 AACR.

Cancer 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 C20H18BrN3, Safety of 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