697763-59-0

Upstream product

• 35320-23-1 (R)-2-aminopropan-1-ol 
• 100-52-7 benzaldehyde 

Downstream Products

• 74609-49-7 (2R)-2-[(phenylmethyl)amino]-1-propanol 
• 458560-75-3 (R)-N-benzyl-2-amino-1-fluoropropane 
• 458560-70-8 (R)-3-benzyl-4-methyl-1,2,3-oxathiazolidine-2-oxide 
• 454248-65-8 (4R)-3-benzyl-4-methyl-1,2,3-oxathiazolidine 2,2-dioxide 
• 1240490-20-3 (R)-N-benzhydryl-alaninol 
• 1240490-34-9 (R)-[benzhydryl-(2-chloro-1-methyl-ethyl)-amino]-acetonitrile 
• 1240490-35-0 (S)-[benzhydryl-(2-chloro-propyl)-amino]-acetonitrile 
• 1240490-23-6 C₁₇H₁₉NO 
• 1240490-24-7 (R)-N-benzhydryl-N-cyanomethyl-alaninol 
• 120800-86-4 (5R)-5-methyl-4-(phenylmethyl)-3-morpholinone 
• 1227911-02-5 (2S,5R)-5-methyl-4-(phenylmethyl)-2-morpholinylmethanol 
• 74571-98-5 (3R)-3-methyl-4-(phenylmethyl)morpholine 

Relevant academic research and scientific papers

Fluoroamines via chiral cyclic sulfamidates

N-benzyl [1,2,3]-oxathiazolidine 2,2-dioxides (cyclic sulfamidates) were synthesized from their corresponding β-amino alcohols and used as substrates in fluorination reactions with tetrabutylammonium fluoride (TBAF). After desulfonation of the intermediates, the N-benzyl fluoroamines were debenzylated by transfer hydrogenolysis with Pd/C to yield (S) and (R)-2-amino-1-fluoropropanes (2b and 3b, respectively, both with 95% ee). The reactions were carried out on multi-gram scale without the need for chromatographic purification of the intermediates. In the presence of carbonate, the (S)- and (R)-N-benzylfluoroamines underwent intramolecular cyclizations in which fluoride was displaced to yield cyclic carbamates 13 and 14.

Optically active, amphiphilic poly(meta -phenylene ethynylene)s: Synthesis, hydrogen-bonding enforced helix stability, and direct AFM observation of their helical structures

Optically active, amphiphilic poly(meta-phenylene ethynylene)s (PPEa) bearing l- or d-alanine-derived oligo(ethylene glycol) side chains connected to the backbone via amide linkages were prepared by microwave-assisted polycondensation. PPEa's exhibited an intense Cotton effect in the π-conjugated main-chain chromophore regions in various polar and nonpolar organic solvents due to a predominantly one-handed helical conformation stabilized by an intramolecular hydrogen-bonding network between the amide groups of the pendants. The stable helical structure was retained in the bulk and led to supramolecular column formation from stacked helices in oriented polymer films as evidenced by X-ray diffraction. Atomic force microscopy was used to directly visualize the helical structures of the polymers in two-dimensional crystalline layers with molecular resolution, and, for the first time, their absolute helical senses could unambiguously be determined.

Structure-based design of potent and selective 3-phosphoinositide-dependent kinase-1 (PDK1) inhibitors

Phosphoinositide-dependent protein kinase-1(PDK1) is a master regulator of the AGC family of kinases and an integral component of the PI3K/AKT/mTOR pathway. As this pathway is among the most commonly deregulated across all cancers, a selective inhibitor of PDK1 might have utility as an anticancer agent. Herein we describe our lead optimization of compound 1 toward highly potent and selective PDK1 inhibitors via a structure-based design strategy. The most potent and selective inhibitors demonstrated submicromolar activity as measured by inhibition of phosphorylation of PDK1 substrates as well as antiproliferative activity against a subset of AML cell lines. In addition, reduction of phosphorylation of PDK1 substrates was demonstrated in vivo in mice bearing OCl-AML2 xenografts. These observations demonstrate the utility of these molecules as tools to further delineate the biology of PDK1 and the potential pharmacological uses of a PDK1 inhibitor.

PROCESS FOR PRODUCTION OF OPTICALLY ACTIVE FLUOROAMINE

Disclosed is a process for producing a protected optically active fluoroamine, which comprises the step of reacting an imine-protected optically active hydroxyamine, an oxazolidine-protected optically active hydroxyamine, or a mixture of the imine-protected optically active hydroxyamine and the oxazolidine-protected optically active hydroxyamine, with sulfuryl fluoride (SO2F2) in the presence of a tertiary amine having a carbon number of 7 to 18 (produced by substituting all of three hydrogen atoms in ammonia by alkyl groups). The desired optically active fluoroamine can be produced by hydrolyzing the protected optically active fluoroamine under acidic conditions.

Synthesis of the azetidinyl-thiazoline fragment of vioprolides A and C

An efficient synthesis of the azetidinyl-thiazoline fragment of the antifungal and cytotoxic macrolides vioprolides A and C is reported. Key steps of the synthesis include formation of the thiazoline by condensation of NAlloc-trans (2S,4R)-4-methylazetidine-2-carbonitrile with L-cysteine and formation of the four-membered ring by intramolecular alkylation of a suitably protected N-Alloc derivative prepared from (R)-alaninol.

CHEMICAL COMPOUNDS

The invention is directed to to substituted indazole derivatives. Specifically, the invention is directed to compounds according to Formula I: wherein R1 - R6 and X are defined herein. The compounds of the invention are inhibitors of PDK1 and can be useful in the treatment of disorders characterized by constitutively activated ACG kinases such as cancer and more specifically leukemia and cancers of the breast, colon, and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PDK1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.