916664-23-8

Upstream product

• 220630-32-0 (2-azido-5-chlorophenyl)methanol 
• 6628-86-0 5-chloro-2-nitrobenzaldehyde 
• 96515-79-6 5-chloro-2-fluorobenzaldehyde 
• 587-04-2 m-Chlorobenzaldehyde 
• 20028-53-9 2-amino-5-chlorobenzaldehyde 

Downstream Products

• 916664-20-5 2-azido-5-chlorobenzaldehyde ehtylene acetal 
• 916664-22-7 2-azido-5-chlorobenzaldehyde ethylene dithioacetal 
• 1126151-03-8 2-(2-azido-5-chlorophenyl)-1,3-oxathiolane 
• 1300044-05-6 2-(2-azido-5-chlorophenyl)-1,3-dihiane 
• 1300044-01-2 2-(5-chloro-2-triphenylphosphoranylideneaminophenyl)-1,3-dioxane 
• 1300044-07-8 2-(5-chloro-2-triphenylphosphoranylideneaminophenyl)-1,3-dithiane 
• 1300044-16-9 6'-chloro-3',3'-diphenylspiro[1,3-dioxane-2,4'(3'H)-quinoline] 
• 1300044-19-2 6'-chloro-3',3'-diphenylspiro[1,3-dithiane-2,4'(3'H)-quinoline] 
• 1300044-25-0 6'-chloro-3'-(4-methylphenyl)spiro[1,3-dioxolane-2,4'(3'H)-quinazoline] 
• 1300044-29-4 C₁₉H₁₆Cl₂N₂O₄ 
• 1300044-03-4 2-(2-azido-5-chlorophenyl)-1,3-dioxane 
• 1279718-30-7 C₈H₇ClN₄O₃ 
• 213542-01-9 5-chloro-3-nitro-1H-indole 
• 1334951-08-4 5-chloro-2-(4-methoxyphenyl)-2H-indazole 

Relevant academic research and scientific papers

One-pot, two-step synthesis of 3,4-dihydroquinazoline-2(1H)-thiones from o-azidobenzenealdehydes, aryl amines and carbon disulfide

A one-pot, two-step method was developed for the synthesis of 3-aryl-3,4-dihydroquinazoline-2(1H)-thiones involving the reductive amination of o-azidobenzaldehydes and aryl amines followed by the Staudinger-aza-Wittig reaction with CS2.

Discovery of Milvexian, a High-Affinity, Orally Bioavailable Inhibitor of Factor XIa in Clinical Studies for Antithrombotic Therapy

Factor XIa (FXIa) is an enzyme in the coagulation cascade thought to amplify thrombin generation but has a limited role in hemostasis. From preclinical models and human genetics, an inhibitor of FXIa has the potential to be an antithrombotic agent with superior efficacy and safety. Reversible and irreversible inhibitors of FXIa have demonstrated excellent antithrombotic efficacy without increased bleeding time in animal models (Weitz, J. I., Chan, N. C. Arterioscler. Thromb. Vasc. Biol. 2019, 39 (1), 7-12). Herein, we report the discovery of a novel series of macrocyclic FXIa inhibitors containing a pyrazole P2′ moiety. Optimization of the series for (pharmacokinetic) PK properties, free fraction, and solubility resulted in the identification of milvexian (BMS-986177/JNJ-70033093, 17, FXIa Ki = 0.11 nM) as a clinical candidate for the prevention and treatment of thromboembolic disorders, suitable for oral administration.

Pd-Catalyzed Four-Component Sequential Reaction Delivers a Modular Fluorophore Platform for Cell Imaging

A Pd-catalyzed cascade reaction of four versatile privileged synthons is described. The sequential reaction involves the formation of five new chemical bonds by concatenating three distinct chemical steps. One of the derivatives exhibited absorption in the visible region, fluorescence with a high quantum yield, and excellent photostability. Its application is explored in live cell imaging, which exhibited cytoplasmic and mitochondrial specific staining with no toxicity.

Cycloaddition and Cascade Radical Reactions for the Synthesis of Trifluoromethylated Tetrahydrobenzodiazepin-3-ones

A reaction sequence involving three-component [3 + 2] cycloaddition of azomethine ylides followed by CuI-catalyzed cascade trifluoromethyl radical addition and cyclization is developed for diastereoselective synthesis of fused-tetrahydrobenzodiazepin-3-ones.

Exploration of Pd-catalysed four-component tandem reaction for one-pot assembly of pyrazolo[1,5-c]quinazolines as potential EGFR inhibitors

A series of pyrazolo[1,5-c]quinazolines as EGFR inhibitors was designed and synthesized by highly efficient and novel multicomponent route involving Pd-catalyzed tandem one-pot four-component reaction. The reaction proceeds with good functional group tolerance under a simple condition with excellent regioselectivity and high efficiency. Target compounds were screened against cancer cell lines MDA-MB-231, A549 and H1299. Of these, 9b and 10b exhibited superior anticancer activity (IC50 2.5 μM) to erlotinib and gefitinib. Synthetics were able to inhibit EGFR mediated kinase activity, induced ROS in cancer cells promoting mitochondrial mediated apoptosis via halting cell cycle progression at G1 phase.

2-[3-(ALKYLSULFONYL)-2H-INDAZOL-2-YL]-3H-IMIDAZO[4,5-B]PYRIDINE DERIVATIVES AND SIMILAR COMPOUNDS AS PESTICIDES

The invention relates to compounds of the formula (Ia) or (Ib), in which Aa, Ab, Ac, Ad, R1, R10 R11, R12, R13, R14, R15, R16, R17, Q, R4, R5, R

FACTOR XIA NEW MACROCYCLE BEARING A NON-AROMATIC P2' GROUP

The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of FXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

NOVEL SUBSTITUTED GLYCINE DERIVED FXIA INHIBITORS

The present invention provides compounds of Formula (I): [INSERT CHEMICAL STRUCTURE HERE] (I) or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of FXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.

Synthesis of 2,3-Disubstituted Quinolines via Ketenimine or Carbodiimide Intermediates

Cyclopenta[b]quinolines and cyclohexa[b]quinolines were prepared via the reactions of α-diazo ketones with N-(2-cyclopropylidenemethylphenyl)phosphanimines and N-(2-cyclobutylidenemethylphenyl) phosphanimine, respectively. The reaction proceeds in a cascade involving ketenimine formation, 6 π-electron ring closure, and 1,3-alkyl shift. A similar approach was developed for the synthesis of dihydropyrrolo-[2,3-b]quinolines from N-(2-cyclopropylidenemethylphenyl)phosphanimines and isocyanates.

DIAMIDE MACROCYCLES AS FACTOR XIA INHIBITORS

The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective factor XIa inhibitors or dual inhibitors of FXIa and plasma kallikrein. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating thromboembolic and/or inflammatory disorders using the same.