Month: November 2022

Boger, Dale L. published the artcileCC-1065 CBI analogs: an example of enhancement of DNA alkylation efficiency through introduction of stabilizing electrostatic interactions, Category: indole-building-block, the main research area is CC1065 CBI analog preparation DNA alkylation.

The three trimethylammonium salts I (R1 and R2 and R3 = H or NMe3+) proved to be 100 times more efficient at alkylating DNA than I (R1 and R2 and R3 = H) and exhibited DNA alkylation efficiencies identical to that of (+)-CC-1065. In addition, the agents I (R1 and R2 = H and R3 = NMe3+) and I (R1 and R3 = H and R2 = NMe3+) exhibited DNA alkylation selectivities identical to that of I (R1 and R2 and R3 = H). This may be attributed to spatially well-defined stabilizing electrostatic interactions between the pos. charged trimethylammonium salt lying on the peripheral face of the agents and the bracketing, neg. charged phosphates located in the DNA backbone that enhance the DNA noncovalent binding affinity without affecting DNA binding or alkylation selectivity. The agent I (R2 and R3 = H and R1 = NMe3+) exhibited an altered and more discriminating AT-rich adenine N3 alkylation selectivity than the other agents that may be attributed to the groove placement of the large trimethylammonium salt.

Bioorganic & Medicinal Chemistry published new progress about Biochemical alkylation. 136818-66-1 belongs to class indole-building-block, name is Methyl 6-nitro-1H-indole-2-carboxylate, and the molecular formula is C10H8N2O4, Category: indole-building-block.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Kulagowski, Janusz J. published the artcile3-[[4-(4-Chlorophenyl)piperazin-1-yl]methyl]-1H-pyrrolo[2,3-b]pyridine: An Antagonist with High Affinity and Selectivity for the Human Dopamine D4 Receptor, Category: indole-building-block, the main research area is dopamine D4 receptor chlorophenylpiperazinylmethyl pyrrolopyridine.

A topol. similarity search of the Merck sample collection using known dopamine agonists and antagonists as probe structures identified indole I as having modest binding selectivity for cloned human dopamine D4 receptors over D2 and D3 subtypes. Optimization of the amino side chain and introduction of a nitrogen atom into the indole nucleus resulted in L-745,870 (II), having high D4 affinity (Ki 0.43 nM) with 2200 and >5000-fold selectivity over D2 and D3 receptors, resp. Also identified in the course of this work was the piperidinol III which demonstrated the opposite selectivity, being 100-fold binding selective for the D2 receptor.

Journal of Medicinal Chemistry published new progress about Dopamine D4 antagonists. 5654-92-2 belongs to class indole-building-block, name is N,N-Dimethyl-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)methanamine, and the molecular formula is C10H13N3, Category: indole-building-block.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Zhao, He published the artcileIndoline and piperazine containing derivatives as a novel class of mixed D2/D4 receptor antagonists. Part 1: Identification and structure-activity relationships, SDS of cas: 41910-64-9, the main research area is dopamine receptor antagonist indoline piperazine derivative preparation SAR.

Optimization of the lead compound 2-[-4-(4-chlorobenzyl)piperazin-1-yl]-1-(2,3-dihydroindol-1-yl)ethanone by systematic structure-activity relation (SAR) studies leads to two potent compounds 2-[-4-(4-chlorobenzyl)piperazin-1-yl]-1-(2-methyl-2,3-dihydroindol-1-yl)ethanone and 2-[-4-(4-chlorobenzyl)piperazin-1-yl]-1-(2-methy-2,3-dihydroindol-1-yl)ethanone. Synthesis and structure-activity relationship as mixed D2/D4 receptor antagonists are reported.

Bioorganic & Medicinal Chemistry Letters published new progress about Dopamine D2 antagonists. 41910-64-9 belongs to class indole-building-block, name is 4-Chloroindoline, and the molecular formula is C8H8ClN, SDS of cas: 41910-64-9.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Qin, Hui published the artcileA Mild and Direct C(sp3)-S Cross-Coupling of Oxindoles with Thiols: Synthesis of Unsymmetrical 3-Thiooxindoles, Computed Properties of 71293-59-9, the main research area is thiooxindole preparation coupling oxindole thiol.

Herein, an operationally simple and mild strategy to construct sulfenation of oxindoles with a series of thiols in the absence of transition metals was developed. This methodol. provides an efficient way to directly form a C-S bond at the C-3 position of oxindoles under mild reaction conditions with a cheap and common solvent and base in moderate to good yields.

Journal of Organic Chemistry published new progress about Cross-coupling reaction. 71293-59-9 belongs to class indole-building-block, name is 5,6-Dichloroindolin-2-one, and the molecular formula is C8H5Cl2NO, Computed Properties of 71293-59-9.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Koenig, Stefan G. published the artcileCopper-Catalyzed Synthesis of Indoles and Related Heterocycles in Renewable Solvents, Recommanded Product: Ethyl 6-cyano-1H-indole-2-carboxylate, the main research area is copper catalyst cross coupling acetamidoacetate bromobenzaldehyde renewable solvent; indolecarboxylate preparation green chem; fused heterocycle preparation green chem.

An efficient one-pot cascade to indoles and related fused heterocycles has been demonstrated in renewable solvents (EtOAc, 2-methyltetrahydrofuran), thereby eliminating the previously required dipolar aprotic solvent. The copper-catalyzed reaction proceeds with a range of bromobenzaldehydes to give products in good yields. E.g., in presence of CuI and Cs2CO3 under nitrogen in EtOAc, cross-coupling of 2-BrC6H4CHO and Et acetamidoacetate gave 59% indole derivative (I). In addition, the external ligand-free cross-coupling methodol. provides convenient access to an investigational treatment for central nervous system disorders.

ACS Sustainable Chemistry & Engineering published new progress about Cross-coupling reaction. 104291-81-8 belongs to class indole-building-block, name is Ethyl 6-cyano-1H-indole-2-carboxylate, and the molecular formula is C12H10N2O2, Recommanded Product: Ethyl 6-cyano-1H-indole-2-carboxylate.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Lillich, Felix F. published the artcileStructure-Based Design of Dual Partial Peroxisome Proliferator-Activated Receptor γ Agonists/Soluble Epoxide Hydrolase Inhibitors, Safety of Methyl 2-methyl-1H-indole-5-carboxylate, the main research area is antitumor structure activity relationship epoxide hydrolase inhibitor.

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 Adipocyte, preadipocyte. 57663-18-0 belongs to class indole-building-block, 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:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Dong, Yanan published the artcileReductive cyanation of organic chlorides using CO2 and NH3 via Triphos-Ni(I) species, Application In Synthesis of 41910-64-9, the main research area is nitrile preparation; chloride organic reductive cyanation.

The reductive cyanation of organic chlorides RCl (R = C6H5, naphthalen-1-yl, cyclohexyl, etc.) using CO2/NH3 as the electrophilic CN source has been described. The use of tridentate phosphine ligand Triphos allows for the nickel-catalyzed cyanation of a broad array of aryl and aliphatic chlorides to produce the desired nitrile products RCN in good yields, and with excellent functional group tolerance. Cheap and bench-stable urea was also shown as suitable CN source, suggesting promising application potential. Mechanistic studies imply that Triphos-Ni(I) species are responsible for the reductive C-C coupling approach involving isocyanate intermediates. This method expands the application potential of reductive cyanation in the synthesis of functionalized nitrile compounds under cyanide-free conditions, which is valuable for safe synthesis of (isotope-labeled) drugs.

Nature Communications published new progress about Antiproliferative agents. 41910-64-9 belongs to class indole-building-block, name is 4-Chloroindoline, and the molecular formula is C8H8ClN, Application In Synthesis of 41910-64-9.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Nishiyama, Takashi published the artcileConcise synthesis of carbazole-1,4-quinones and evaluation of their antiproliferative activity against HCT-116 and HL-60 cells, Application In Synthesis of 136818-66-1, the main research area is carbazolequinone preparation antiproliferative human; indole allyl alc tandem ring closing metathesis dehydrogenation; Antiproliferative activity; Carbazole-1,4-quinone; Koeniginequinone A; Koeniginequinone B.

A convenient synthesis of carbazole-1,4-quinone alkaloid koeniginequinones A and B using a tandem ring-closing metathesis with the dehydrogenation reaction sequence under an O2 atmosphere as an important step is reported. Using this method, carbazole-1,4-quinones substituted at the 5-, 6-, 7-, and/or 8-positions I (R1 = R2 = H, CH3; R3 = H, 6-OCH3, 5,6-(OCH3)2, 7-CH3, 6-NO2, etc.; R4 = H, MOM) have been synthesized. Moreover, 24 compounds, including koeniginequinones A and B, have been evaluated for their antiproliferative activity against HCT-116 and HL-60 cells, and the 6-nitro analog exhibited the most potent activity against both tumor cell types.

European Journal of Medicinal Chemistry published new progress about Antiproliferative agents. 136818-66-1 belongs to class indole-building-block, name is Methyl 6-nitro-1H-indole-2-carboxylate, and the molecular formula is C10H8N2O4, Application In Synthesis of 136818-66-1.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

See, Cheng Shang published the artcileDiscovery of the cancer cell selective dual acting anti-cancer agent (Z)-2-(1H-indol-3-yl)-3-(isoquinolin-5-yl)acrylonitrile (A131), Application of N,N-Dimethyl-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)methanamine, the main research area is indolyl isoquinolinyl acrylonitrile analogs preparation cancer mitosis autophagy; Antimitotic; Antiproliferative; Antitumor; Tumor-selective.

Selective targeting of cancer cells over normal cells is a key objective of targeted therapy. However few approaches achieve true mechanistic selectivity resulting in debilitating side effects and dose limitation. In this work we describe the discovery of A131 (4a), a new agent with an unprecedented dual mechanism of action targeting both mitosis and autophagy. Compound 4a was first identified in a phenotypic screen in which HeLa cells treated with 4a manifested mitotic arrest along with formation of multiple vesicles. Further investigations showed that 4a causes an increase in mitotic marker pH3 and autophagy marker LC3. Importantly 4a induces cell death in cancer cells while sparing normal cells which regrow after 4a is removed. Dual activities against pH3 and LC3 markers are required for cancer cell selectivity. An extensive SAR investigation confirmed 4a as the optimal dual inhibitor with potency against a panel of 30 cancer cell lines (average antiproliferative GI50 1.5μM). In a mouse model of paclitaxel-resistant colon cancer, 4a showed 74% tumor growth inhibition when administered at a dose of 20mg/kg IP twice a day.

European Journal of Medicinal Chemistry published new progress about Antiproliferative agents. 5654-92-2 belongs to class indole-building-block, name is N,N-Dimethyl-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)methanamine, and the molecular formula is C10H13N3, Application of N,N-Dimethyl-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)methanamine.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Maddela, Srinubabu published the artcileSynthesis of isatin-quinoline conjugates as possible biologically active agents, Recommanded Product: 4,5-Dichloroisatin, the main research area is isatin quinoline conjugate preparation antibacterial antifungal antiinflammatory; quinolinyl hydrazide isatin condensation.

A series of 12 new quinoline-3-carbohydrazide derivatives I (R = H, 5-F, 4-Cl, 7-Cl, etc.) were synthesized by the condensation of quinolinyl hydrazide with different isatins. The synthesized compounds were evaluated for in vitro antimicrobial and in vivo anti-inflammatory activity. Tested compounds exhibited moderate to good antibacterial and antifungal activity. Evaluation of the compounds revealed remarkable anti-inflammatory activity and were comparable with standard, indomethacin. Compounds I (R = 5-O2N, 5-F, 7-Cl, 4-Cl) inhibited paw edema in a carrageenan-induced rat hind paw edema model.

Toxicological & Environmental Chemistry published new progress about Anti-inflammatory agents. 1677-47-0 belongs to class indole-building-block, name is 4,5-Dichloroisatin, and the molecular formula is C8H3Cl2NO2, Recommanded Product: 4,5-Dichloroisatin.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles