214758-90-4

Upstream product

• 13816-33-6 p-Cyanocumen 
• 1443-80-7 4-cyanophenyl methyl ketone 
• 3058-39-7 4-iodobenzonitrile 
• 77802-22-3 4-(2-hydroxypropan-2-yl)benzenecarbonitrile 
• 917-64-6 methyl magnesium iodide 
• 366-84-7 ethyl 4-(aminomethyl)benzoate 

Downstream Products

• 714975-80-1 (S)-2-Methyl-butyric acid (1S,3R,7S,8S,8aR)-8-(2-{(4R,6R)-3-[4-(1-hydroxy-1-methyl-ethyl)-benzyl]-4-methoxycarbonylmethyl-2-oxo-[1,3]oxazinan-6-yl}-ethyl)-3,7-dimethyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester 
• 214756-87-3 2-(3-Fluoro-phenoxy)-N-[4-(1-hydroxy-1-methyl-ethyl)-benzyl]-nicotinamide 
• 214757-21-8 2-(2,4-Difluoro-phenoxy)-N-[4-(1-hydroxy-1-methyl-ethyl)-benzyl]-nicotinamide 
• 214756-93-1 N-[4-(1-Hydroxy-1-methyl-ethyl)-benzyl]-2-(3-methylsulfanyl-phenoxy)-nicotinamide 
• 214757-19-4 N-[4-(1-Hydroxy-1-methyl-ethyl)-benzyl]-2-(3-trifluoromethoxy-phenoxy)-nicotinamide 
• 214757-29-6 2-(3,5-Difluoro-phenoxy)-N-[4-(1-hydroxy-1-methyl-ethyl)-benzyl]-nicotinamide 
• 214757-81-0 2-(3-Dimethylcarbamoyl-phenoxy)-N-[4-(1-hydroxy-1-methyl-ethyl)-benzyl]-nicotinamide 
• 214757-34-3 2-(3-Cyano-4-fluoro-phenoxy)-N-[4-(1-hydroxy-1-methyl-ethyl)-benzyl]-nicotinamide 
• 214757-22-9 2-(3,4-Difluoro-phenoxy)-N-[4-(1-hydroxy-1-methyl-ethyl)-benzyl]-nicotinamide 
• 214757-83-2 N-[4-(1-Hydroxy-1-methyl-ethyl)-benzyl]-2-[3-(2,2,2-trifluoro-1-hydroxy-ethyl)-phenoxy]-nicotinamide 
• 214757-85-4 2-(3-Carbamoyl-phenoxy)-N-[4(1-hydroxy-1-methyl-ethyl)-benzyl]-nicotinamide 
• 214756-71-5 N-[4-(1-Hydroxy-1-methyl-ethyl)-benzyl]-2-(3-trifluoromethyl-phenoxy)-nicotinamide 
• 214756-73-7 2-(3-Chloro-phenoxy)-N-[4-(1-hydroxy-1-methyl-ethyl)-benzyl]-nicotinamide 
• 214757-89-8 N-(4-(1-Hydroxy-1-methyl-ethyl-)-benzyl)-2-(2-methyl-benzothiazol-5-yloxy)-nicotinamide 

Relevant academic research and scientific papers

Scalable process for 4-(2-hydroxy-2-methyl)-ethyl-benzylamine

The preparation of the title compound has been revisited and improved. Starting from inexpensive cuminonitrile, 4-(2-hydroxy-2-methyl)-ethyl- benzylamine is obtained in a scalable two-step process with an overall yield of 55%. Copyright Taylor & Francis G

POSITIVE ALLOSTERIC MODULATORS OF THE MUSCARINIC ACETYLCHOLINE RECEPTOR M4

Disclosed herein are tricyclic compounds, including thieno[2,3-d:4,5-d′]dipyrimidin-4-amine and pyrido[4′,3′:4,5]thieno[2,3-d]pyrimidin-8-amine compounds, which may be useful as positive allosteric modulators of the muscarinic acetylcholine receptor Msub

POSITIVE ALLOSTERIC MODULATORS OF THE MUSCARINIC ACETYLCHOLINE RECEPTOR M4

Disclosed herein are tricyclic compounds, including 3-(difluoromethyl)-4-methylpyrimido[4',5':4,5]thieno[2,3-c]pyridazin-8-amine compounds, which may be useful as positive allosteric modulators of the muscarinic acetylcholine receptor M4 (mAChR

POSITIVE ALLOSTERIC MODULATORS OF THE MUSCARINIC ACETYLCHOLINE RECEPTOR M4

Disclosed herein are pyrido[3',2':4,5]thieno[2,3-d]pyridazin-8-amine and thieno[2,3-c:4,5-d']dipyridazin-8-amine compounds, which may be useful as positive allosteric modulators of the muscarinic acetylcholine receptor M4 (mAChR M4).

POSITIVE ALLOSTERIC MODULATORS OF THE MUSCARINIC ACETYLCHOLINE RECEPTOR M4

Disclosed herein are thieno[2,3-b:5,4-c']dipyridin-8-amine and pyrido[4',3':4,5]thieno[2,3-c]pyridazin-8-amine compounds, which may be useful as positive allosteric modulators of the muscarinic acetylcholine receptor M4 (mAChR M4). A

POSITIVE ALLOSTERIC MODULATORS OF THE MUSCARINIC ACETYLCHOLINE RECEPTOR M4

Disclosed herein are 2,4-dimethylquinoline-6-carboxamide compounds and 3,4- dimethylcinnoline-6-carboxamide compounds, which may be useful as positive allosteric modulators of the muscarinic acetylcholine receptor M4(mAChR M4). Also disclosed herein are methods of making the compounds, pharmaceutical compositions comprising the compounds, and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions.

POSITIVE ALLOSTERIC MODULATORS OF THE MUSCARINIC ACETYLCHOLINE RECEPTOR M4

Disclosed herein are tricyclic compounds, including pyrimido[4′,5′:4,5]thieno[2,3-c]pyridazine-8-amine, pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine-4-amine, pyrazino[2′,3′:4,5]thieno[3,2-d]pyrimidin-4-amine, pyrido[3′,2′:4,5]furo[3, 2-d]pyrimidin-4-amine, and pyrimido[4′,5′:4,5]furo[2,3-c]pyridazin-8-amine compounds, which may be useful as positive allosteric modulators of the muscarinic acetylcholine receptor M4 (mAChR M4). Also disclosed herein are methods of making the compounds, pharmaceutical compositions comprising the compounds, and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions.

Selective targeting of dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (Dc-Sign) with mannose-based glycomimetics: Synthesis and interaction studies of bis(benzylamide) derivatives of a pseudomannobioside

Dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and Langerin are C-type lectins of dendritic cells (DCs) that share a specificity for mannose and are involved in pathogen recognition. HIV is known to use DC-SIGN on DCs to facilitate transinfection of T-cells. Langerin, on the contrary, contributes to virus elimination; therefore, the inhibition of this latter receptor is undesired. Glycomimetic molecules targeting DC-SIGN have been reported as promising agents for the inhibition of viral infections and for the modulation of immune responses mediated by DC-SIGN. We show here for the first time that glycomimetics based on a mannose anchor can be tuned to selectively inhibit DC-SIGN over Langerin. Based on structural and binding studies of a mannobioside mimic previously described by us (2), a focused library of derivatives was designed. The optimized synthesis gave fast and efficient access to a group of bis(amides), decorated with an azide-terminated tether allowing further conjugation. SPR inhibition tests showed improvements over the parent pseudomannobioside by a factor of 3-4. A dimeric, macrocyclic structure (11) was also serendipitously obtained, which afforded a 30-fold gain over the starting compound (2). The same ligands were tested against Langerin and found to exhibit high selectivity towards DC-SIGN. Structural studies using saturation transfer difference NMR spectroscopy (STD-NMR) were performed to analyze the binding mode of one representative library member with DC-SIGN. Despite the overlap of some signals, it was established that the new ligand interacts with the protein in the same fashion as the parent pseudodisaccharide. The two aromatic amide moieties showed relatively high saturation in the STD spectrum, which suggests that the improved potency of the bis(amides) over the parent dimethyl ester can be attributed to lipophilic interactions between the aromatic groups of the ligand and the binding site of DC-SIGN. Receptor targeting: For the first time glycomimetics based on a mannose anchor have been tuned to selectively inhibit DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin) over Langerin. Based on structural and binding studies of a mannobioside mimic previously described, a focused library of derivatives was designed (see figure). Copyright

PYRIDO[2,3-D]PYRIMIDINE-2,4-DIAMINES AS PDE 2 INHIBITORS

The invention provides compounds of formula (I) prodrugs thereof, and the pharmaceutically acceptable salts of the compounds or prodrugs, wherein n, X, and Y are as defined herein; pharmaceutical compositions thereof; combinations thereof; and uses thereo

Pyrimidine carboxamides useful as inhibitors of pde4 isozymes

Compounds of formula (1.0.0) are described, as well as the usefulness of a pharmaceutical composition for treating inflammatory, respiratory and allergic diseases and conditions, especially asthma; chronic obstructive pulmonary disease (COPD) including chronic bronchitis, emphysema, and bronchiectasis; chronic rhinitis; and chronic sinusitis.