329943-13-7

Upstream product

• 6952-59-6 3-cyanobromobenzene 
• 201230-82-2 carbon monoxide 
• 6638-79-5 N,O-dimethylhydroxylamine*hydrochloride 
• 15226-74-1 dicobalt octacarbonyl 
• 69113-59-3 3-iodobenzonitrile 
• 1711-11-1 3-cyanobenzoyl chloride 
• 1877-72-1 3-Cyanobenzoic acid 
• 16645-06-0 N,N-dimethylhydroxylamine hydrochloride 
• 1117-97-1 N,0-dimethylhydroxylamine 

Downstream Products

• 861722-24-9 3-(pyridazin-4-yl-acetyl)-benzonitrile 
• 861722-25-0 3-(pyrimidin-4-yl-acetyl)-benzonitrile 
• 1089278-58-9 3-[(2-chloro-4-pyrimidinyl)acetyl]benzonitrile 
• 60694-67-9 3-cyano-4'-methoxybenzophenone 
• 1056465-47-4 KPU-244-B₁ 
• 1056465-94-1 C₃₂H₃₄N₄O₆ 
• 1056465-93-0 C₂₀H₂₁NO₄ 
• 67362-99-6 3-(benzo[d]thiazol-2-yl)benzonitrile 
• 108440-76-2 3-(3-fluorobenzoyl)benzaldehyde 
• 1266888-39-4 3-(2-fluorobenzoyl)benzaldehyde 
• 1236141-97-1 (3Z,6Z)-3-((5-tert-butyl-1H-imidazol-4-yl)methylene)-6-(3-(3-fluorobenzoyl)benzylidene)piperazine-2,5-dione 
• 1385033-48-6 3-(3-fluorobenzoyl)benzonitrile 
• 1385033-47-5 3-(2-fluorobenzoyl)benzonitrile 
• 1056465-92-9 C₂₀H₂₀N₂O₃ 

Relevant academic research and scientific papers

Fluoro-Substituted Methyllithium Chemistry: External Quenching Method Using Flow Microreactors

The external quenching method based on flow microreactors allows the generation and use of short-lived fluoro-substituted methyllithium reagents, such as fluoromethyllithium, fluoroiodomethyllithium, and fluoroiodostannylmethyllithium. Highly chemoselective reactions have been developed, opening new opportunities in the synthesis of fluorinated molecules using fluorinated organometallics.

A small molecule inhibitor of PCSK9 that antagonizes LDL receptor binding via interaction with a cryptic PCSK9 binding groove

Proprotein convertase (PC) subtilisin kexin type 9 (PCSK9) inhibits the clearance of low density lipoprotein (LDL) cholesterol from plasma by directly interacting with the LDL receptor (LDLR). As the interaction promotes elevated plasma LDL cholesterol levels and a predisposition to cardiovascular disease (CVD), it has attracted much interest as a therapeutic target. While anti-PCSK9 monoclonal antibodies have been successful in the treatment of hypercholesteremia by decreasing CVD risk, their high cost and a requirement for injection have prohibited widespread use. The advent of an orally bioavailable small molecule inhibitor of the PCSK9-LDLR interaction is an attractive alternative, however efforts have been tempered as the binding interface is unfavourable for binding by small organic molecules. Despite its challenging nature, we report herein the discovery of compound 3f as a small molecule inhibitor of PCSK9. The kinase inhibitor nilotinib emerged from a computational screen that was applied to identify compounds that may bind to a cryptic groove within PCSK9 and proximal to the LDLR-binding interface. A subsequent in vitro PCSK9-LDLR binding assay established that nilotinib was a bona fide but modest inhibitor of the interaction (IC50 = 9.8 μM). Through multiple rounds of medicinal chemistry, 3f emerged as a lead-like molecule by demonstrating disruption of the PCSK9-LDLR interaction at nanomolar levels in vitro (IC50 = 537 nM) with no inhibitory activity (IC50 > 10 μM) against a small panel of kinases. Compound 3f restored LDL uptake by liver cells at sub-micromolar levels and demonstrated excellent bioavailability when delivered subcutaneously in mice. Most significantly, compound 3f lowered total cholesterol levels in the plasma of wild-type mice, thereby providing proof-of-concept that the notion of a small molecule inhibitor against PCSK9 is therapeutically viable.

HETEROCYCLIC INHIBITORS OF PCSK9

This application relates to chemical compounds which may act as inhibitors of, or which may otherwise modulate the activity of, PCSK9, or a pharmaceutically acceptable salt, solvate, prodrug or polymorph thereof, and to compositions and formulations comprising such compounds, and methods of using and making such compounds. Compounds include compounds of Formula (I): (I) wherein A, D and Q are described herein.

One-Pot Direct Synthesis of Weinreb Amides from Aryl and Hetero Aryl Halides Using Co 2(CO) 8 as an Effective CO Source under Conventional Thermal Heating

A successful protocol for the synthesis of Weinreb amides directly from aryl halides via aminocarbonylation with N,O-dimethyl hydroxylamine using Co2(CO)8 as an in situ CO source has been demonstrated. The effects of various reaction parameters such as temperature, base, and CO source have also been investigated and optimized. GRAPHICAL ABSTRACT.

ANALOGS OF DEHYDROPHENYLAHISTINS AND THEIR THEAPEUTIC USE

Compounds represented by the following structure (II) are disclosed: as are methods for making such compounds. Compositions and methods for treating various disease conditions including cancer and non-cancer diseases associated with vascular proliferation are also disclosed.

Palladium-catalyzed carbonylation reactions of aryl bromides at atmospheric pressure: A general system based on xantphos

(Chemical Equation Presented) A method for the Pd-catalyzed carbonylation of aryl bromides has been developed using Xantphos as the ligand. This method is effective for the direct synthesis of Weinreb amides, 1° and 2° benzamides, and methyl esters from the corresponding aryl bromides at atmospheric pressure. In addition, a putative catalytic intermediate, (Xanphos)Pd(Br)benzoyl, was prepared and an X-ray crystal structure was obtained revealing an unusual cis-coordination mode of Xantphos in this palladium-acyl complex.

Convenient method for the preparation of weinreb amides via PD-catalyzed aminocarbonylation of aryl bromides at atmospheric pressure

(Chemical Equation Presented) The direct transformation of aryl bromides into the corresponding Weinreb amides via Pd-catalyzed aminocarbonylation at atmospheric pressure is reported.

THIAZOLE DERIVATIVES AS A2B ANTAGONISTS

Compounds of formula (I) in free or salt form, where Ar is phenyl substituted by one or more substituents selected from halogen, cyano and C1- C8-haloalkyl, or naphthyl, R1 is hydrogen, phenyl optionally substituted by one

New HIV-1 replication inhibitors of the styryquinoline class bearing aroyl/acyl groups at the C-7 position: Synthesis and biological activity

Novel variants of HIV-1 replication inhibitors of the styrylquinoline class harboring aroyl/acyl group at the C-7 position have been synthesized. In sharp contrast with styrylquinolines bearing a carboxylic acid group at C-7, these compounds proved to be inactive toward HIV-1 integrase in in vitro assays.