851334-98-0

Upstream product

• 1246765-31-0 methyl 2-ethoxy-4-iodobenzoate 
• 73183-34-3 bis(pinacol)diborane 
• 18179-39-0 methyl 4-iodosalicylate 

Downstream Products

• 1254328-53-4 methyl 4-(3-amino-6-(3,4,5-trimethoxyphenyl)pyrazin-2-yl)-2-ethoxybenzoate 
• 1608471-45-9 (R)-4-(1-(4-cyano-3-methylphenyl)-5-cyclopentyl-4,5-dihydro-1H-pyrazol-3-yl)-2-ethoxybenzoic acid 
• 1637740-91-0 (R)-methyl 4-(1-(4-cyano-3-methylphenyl)-5-cyclopentyl-4,5-dihydro-1H-pyrazol-3-yl)-2-ethoxybenzoate 

Relevant academic research and scientific papers

SSTR5 ANTAGONISTS

This disclosure is directed, at least in part, to SSTR5 antagonists useful for the treatment of conditions or disorders involving the gut-brain axis. In some embodiments, the SSTR5 antagonists are gut-restricted compounds. In some embodiments, the condition or disorder is a metabolic disorder, such as diabetes, obesity, nonalcoholic steatohepatitis (NASH), or a nutritional disorder such as short bowel syndrome.

Identification of (R)-6-(1-(4-cyano-3-methylphenyl)-5-cyclopentyl-4,5- dihydro-1H-pyrazol-3-yl)-2-methoxynicotinic acid, a highly potent and selective nonsteroidal mineralocorticoid receptor antagonist

A novel series of nonsteroidal mineralocorticoid receptor (MR) antagonists identified as part of our strategy to follow up on the clinical candidate PF-03882845 (2) is reported. Optimization departed from the previously described pyrazoline 3a and focused on improving the selectivity for MR versus the progesterone receptor (PR) as an approach to avoid potential sex-hormone-related adverse effects and improving biopharmaceutical properties. From this effort, (R)-14c was identified as a potent nonsteroidal MR antagonist (IC50 = 4.5 nM) with higher than 500-fold selectivity versus PR and other related nuclear hormone receptors, with improved solubility as compared to 2 and pharmacokinetic properties suitable for oral administration. (R)-14c was evaluated in vivo using the increase of urinary Na+/K+ ratio in rat as a mechanism biomarker of MR antagonism. Treatment with (R)-14c by oral administration resulted in significant increases in urinary Na +/K+ ratio and demonstrated this novel compound acts as an MR antagonist.

SPIRO AZETIDINE ISOXAZOLE DERIVATIVES AND THEIR USE AS SSTR5 ANTAGONISTS

Provided is a compound represented by the following formula (1) or a salt thereof, which has an SSTR5 antagonistic action: wherein each symbol has the same definition as in the specification.

Aminopyrazine inhibitors binding to an unusual inactive conformation of the mitotic kinase Nek2: SAR and structural characterization

We report herein the first systematic exploration of inhibitors of the mitotic kinase Nek2. Starting from HTS hit aminopyrazine 2, compounds with improved activity were identified using structure-based design. Our structural biology investigations reveal two notable observations. First, 2 and related compounds bind to an unusual, inactive conformation of the kinase which to the best of our knowledge has not been reported for other types of kinase inhibitors. Second, a phenylalanine residue at the center of the ATP pocket strongly affects the ability of the inhibitor to bind to the protein. The implications of these observations are discussed, and the work described here defines key features for potent and selective Nek2 inhibition, which will aid the identification of more advanced inhibitors of Nek2.

4, 5-DIHYDRO-LH-PYRAZOLE COMPOUNDS AND THEIR PHARMACEUTICAL USES

Mineralocorticoid receptor antagonists (MRa), pharmaceutical compositions containing such inhibitors and the use of such inhibitors to treat, for example, diabetic nephropathy and hypertension in mammals, including humans.

AMINO ALCOHOL DERIVATIVE, MEDICINAL COMPOSITION CONTAINING THE SAME, AND USE OF THESE

The present invention provides compounds represented by general formula (I): a prodrug thereof, or pharmaceutical acceptable salts thereof, wherein R1 is hydrogen or lower alkyl; each of R2 and R3 is independently hydrogen or lower alkyl; each of R4, R5 and R6 is independently hydrogen, halogen, lower alkyl or lower alkoxy; R7 is hydrogen or lower alkyl; R8 is hydrogen, halogen, lower alkyl, lower alkoxy, etc; R9 is -COR10, -A1-COR10, -O-A2-COR10, etc; Ar is optionally substituted phenyl or heteroaryl; and A is a bond, -OCH2-, etc, which exhibit potent and selective β3-adrenoceptor stimulating activities. The present invention also provides pharmaceutical compositions containing said compound, and uses thereof.