859169-20-3

Usage

Uses

4-Ethoxycarbonylmethylphenylboronic acid, pinacol ester

Upstream product

• 5764-82-9 bromo(2-ethoxy-2-oxoethyl)zinc 
• 195062-61-4 4-chlorophenylboronic acid pinacol ester 
• 1878-68-8 2-(4-bromophenyl)-acetic acid 
• 15250-46-1 ethyl (4-iodophenyl)acetate 
• 73183-34-3 bis(pinacol)diborane 
• 797755-07-8 2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetic acid 
• 64-17-5 ethanol 
• 14062-25-0 Ethyl 4-bromophenylacetate 

Downstream Products

• 859169-21-4 [4-(3,6-dihydro-2H-pyran-4-yl)-phenyl]-acetic acid ethyl ester 
• 1204651-82-0 2-amino-1-ethyl-7-{4-[2-({[(2S)-1-ethyl-4,4-difluoropyrrolidin-2-yl]methyl}-amino)-2-oxoethyl]phenyl}-N-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxamide 
• 1204651-66-0 2-amino-1-ethyl-7-{4-[2-({[(2S,4R)-1-ethyl-4-fluoropyrrolidin-2-yl]methyl}-amino)-2-oxoethyl]phenyl}-N-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxamide 
• 1204651-88-6 2-amino-1-ethyl-N-methyl-7-{4-[2-({[4-(1-methylethyl)morpholin-3-yl]-methyl}amino)-2-oxoethyl]phenyl}-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxamide 
• 1204651-57-9 {4-[7-Amino-8-ethyl-6-(methyl carbamoyl)-5-oxo-5,8-dihydro-1,8-naphthyridin-2-yl]phenyl}acetic acid 
• 1204651-65-9 C₂₀H₁₉FN₄O₃ 
• 1204651-56-8 Ethyl {4-[7-amino-8-ethyl-6-(methylcarbamoyl)-5-oxo-5,8-dihydro-1,8-naphthyridin-2-yl]phenyl}acetate 
• 1428333-96-3 N-[5-(aminosulfonyl)-4-methyl-1,3-thiazol-2-yl]-N-methyl-2-[4-(2-pyridinyl)-phenyl]acetamide mono methanesulfonic acid 
• 51061-67-7 (4-pyridine-2-yl-phenyl)acetic acid 
• 1284212-82-3 C₂₅H₂₈N₂O₅ 
• 1308917-77-2 (4-{7-Amino-8-ethyl-5-oxo-6-[1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-5,8-dihydro-[1,8]naphthyridin-2-yl}-phenyl)-acetic acid 
• 1308917-78-3 C₂₉H₃₇N₅O₄Si 
• 1308917-80-7 2-{4-[7-amino-8-ethyl-5-oxo-6-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl)-5,8-dihydro-1,8-naphthyridin-2-yl]phenyl}-N-[(4-cyclopropylmorpholin-3-yl)methyl]acetamide 
• 1290056-76-6 benzyl 3-(1-(2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetyl)piperidin-4-yl)benzylcarbamate 

Relevant academic research and scientific papers

Coupling of Reformatsky Reagents with Aryl Chlorides Enabled by Ylide-Functionalized Phosphine Ligands

The coupling of aryl chlorides with Reformatsky reagents is a desirable strategy for the construction of α-aryl esters but has so far been substantially limited in the substrate scope due to many challenges posed by various possible side reactions. This limitation has now been overcome by the tailoring of ylide-functionalized phosphines to fit the requirements of Negishi couplings. Record-setting activities were achieved in palladium-catalyzed arylations of organozinc reagents with aryl electrophiles using a cyclohexyl-YPhos ligand bearing an ortho-tolyl-substituent in the backbone. This highly electron-rich, bulky ligand enables the use of aryl chlorides in room temperature couplings of Reformatsky reagents. The reaction scope covers diversely functionalized arylacetic and arylpropionic acid derivatives. Aryl bromides and chlorides can be converted selectively over triflate electrophiles, which permits consecutive coupling strategies.

NOVEL TRICYCLIC COMPOUNDS AS ANTICANCER AGENTS

The present invention is directed to tricyclic compounds, pharmaceutically acceptable compositions comprising compounds of the invention and methods of using said compositions in the treatment of various disorders.

Biphenyl Pyridazinone Derivatives as Inhaled PDE4 Inhibitors: Structural Biology and Structure-Activity Relationships

Cyclic nucleotide cAMP is a ubiquitous secondary messenger involved in a plethora of cellular responses to biological agents involving activation of adenylyl cyclase. Its intracellular levels are tightly controlled by a family of cyclic nucleotide degrading enzymes, the PDEs. In recent years, cyclic nucleotide phosphodiesterase type 4 (PDE4) has aroused scientific attention as a suitable target for anti-inflammatory therapy in respiratory diseases, particularly in the management of asthma and COPD. Here we describe our efforts to discover novel, highly potent inhaled inhibitors of PDE4. Through structure based design, with the inclusion of a variety of functional groups and physicochemical profiles in order to occupy the solvent-filled pocket of the PDE4 enzyme, we modified the structure of our oral PDE4 inhibitors to reach compounds down to picomolar enzymatic potencies while at the same time tackling successfully an uncovered selectivity issue with the adenosine receptors. In vitro potencies were demonstrated in a rat lung neutrophilia model by administration of a suspension with a Penn-Century MicroSprayer Aerosolizer.

TRICYCLIC COMPOUNDS AS ANTICANCER AGENTS

The present invention is directed to tricyclic compounds (I), pharmaceutically acceptable compositions comprising compounds of the invention and methods of using said compositions in the treatment of various disorders.

PHTHALAZINONES AND ISOQUINOLINONES AS ROCK 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 ROCK inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating cardiovascular, smooth muscle, oncologic, neuropathologic, autoimmune, fibrotic, and/or inflammatory disorders using the same.

N-ARYLTRIAZOLE COMPOUNDS AS LPAR ANTAGONISTS

Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of inflammatory diseases and disorders such as, for example, pulmonary fibrosis

PYRIDINO-PYRIDINONE DERIVATIVES, PREPARATION AND THERAPEUTIC USE THEREOF

The present invention relates to derivatives of pyridino-pyridinones, and to their preparation and use thereof, having activity as inhibitors of kinase activity of receptors for PDGF (platelet derived growth factors) ligands and optionally of receptors for the FLT3 (fms-like tyrosine kinase receptor) ligand receptors, said derivatives comprising compounds of formula (I): wherein the various substituent groups are more specifically defined herein. The compounds are suitable as therapeutics for the treatment of various proliferative diseases.

Discovery of highly selective and orally active lysophosphatidic acid receptor-1 antagonists with potent activity on human lung fibroblasts

Lysophosphatidic acid is a class of bioactive phospholipid that mediates most of its biological effects through LPA receptors, of which six isoforms have been identified. The recent results from LPA1 knockout mice suggested that blocking LPA1 signaling could provide a potential novel approach for the treatment of idiopathic pulmonary fibrosis. Here, we report the design and synthesis of pyrazole- and triazole-derived carbamates as LPA1-selective and LPA1/3 dual antagonists. In particular, compound 2, the most selective LPA1 antagonist reported, inhibited proliferation and contraction of normal human lung fibroblasts (NHLF) following LPA stimulation. Oral dosing of compound 2 to mice resulted in a dose-dependent reduction of plasma histamine levels in a murine LPA challenge model. Furthermore, we applied our novel antagonists as chemistry probes and investigated the contribution of LPA1/2/3 in mediating the pro-fibrotic responses. Our results suggest LPA1 as the major receptor subtype mediating LPA-induced proliferation and contraction of NHLF.

COFERONS AND METHODS OF MAKING AND USING THEM

The present invention is directed to a monomer useful in preparing therapeutic compounds. The monomer includes one or more pharmacophores which potentially binds to a target molecule with a dissociation constant of less than 300 μM and a linker element connected to the pharmacophore. The linker element has a molecular weight less than 500 daltons, is connected, directly or indirectly through a connector, to the pharmacophore.

3-(5-Amino-6-oxo-1,6-dihydropyridazin-3-yl)-biphenyl derivatives as PDE4 inhibitors

New pyridazin-3(2H)-one derivatives having the chemical structure of formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of the phosphodiesterase IV (PDE4).