176039-99-9

Upstream product

• 51-67-2 tyrosamine 
• 103-80-0 phenylacetyl chloride 
• 103-82-2 phenylacetic acid 

Downstream Products

• 176040-03-2 4-[2-(benzylcarbonylamino)ethyl]phenyl 2,4-di-O-methyl-3-O-{4-O-benzyl-2-O-methyl-3-O-[4-O-acetyl-2-O-methyl-3-O-(3-O-benzyl-2,6-dideoxy-4-O-methyl-2-phenylthio-α-D-arabino-hexopyranosyl)-α-L-fucopyranosyl]-α-L-rhamnopyranosyl}-α-L-rhamnopyranoside 
• 176040-04-3 4-[2-(benzylcarbonylamino)ethyl]phenyl 2,4-di-O-methyl-3-O-{4-O-benzyl-2-O-methyl-3-O-[4-O-acetyl-2-O-methyl-3-O-(3-O-benzyl-2,6-dideoxy-4-O-methyl-α-D-arabino-hexopyranosyl)-α-L-fucopyranosyl]-α-L-rhamnopyranosyl}-α-L-rhamnopyranoside 
• 176039-75-1 C₄₇H₆₃NO₁₅ 
• 176040-01-0 4-<2-(benzylcarbonylamino)ethyl>phenyl 2,4-di-O-methyl-α-L-rhamnopyranoside 
• 176040-00-9 Acetic acid (2S,3S,4R,5R,6S)-3,5-dimethoxy-2-methyl-6-[4-(2-phenylacetylamino-ethyl)-phenoxy]-tetrahydro-pyran-4-yl ester 

Relevant academic research and scientific papers

Synthesis and biological evaluation of N-acylated tyramine sulfamates containing C–F bonds as steroid sulfatase inhibitors

Steroid sulfatase (STS) is responsible for the hydrolysis of biologically inactive sulfated steroids into their active un-sulfated forms and promotes the growth of various hormone-dependent cancers (e.g., breast cancer). Therefore, the STS enzyme is a promising therapeutic target for the treatment of steroid-sensitive cancers. Herein, we report the synthesis and biological evaluation of sulfamate analogs as potential STS inhibitors based on N-acylated tyramines that contain C–F bonds. The inhibitory effects of the analogs were tested using STS isolated from human placenta. Of the analogs tested, 4-(2-perfluoroundecanoylaminoethyl)-phenyl sulfamate, 5r, demonstrated the greatest inhibitory effect, with an IC50 value of 2.18?μm (IC50 value of 2.13?μm for coumarin-7-O-sulfamate was used as a reference). These findings were supported by the results our computational analyses performed using molecular docking techniques.

Direct amidation of carboxylic acids catalyzed by ortho-iodo arylboronic acids: Catalyst optimization, scope, and preliminary mechanistic study supporting a peculiar halogen acceleration effect

The importance of amides as a component of biomolecules and synthetic products motivates the development of catalytic, direct amidation methods employing free carboxylic acids and amines that circumvent the need for stoichiometric activation or coupling reagents. ortho-Iodophenylboronic acid 4a has recently been shown to catalyze direct amidation reactions at room temperature in the presence of 4A molecular sieves as dehydrating agent. Herein, the arene core of ortho-iodoarylboronic acid catalysts has been optimized with regards to the electronic effects of ring substitution. Contrary to the expectation, it was found that electron-donating substituents are preferable, in particular, an alkoxy substituent positioned para to the iodide. The optimal new catalyst, 5-methoxy-2-iodophenylboronic acid (MIBA, 4f), was demonstrated to be kinetically more active than the parent des-methoxy catalyst 4a, providing higher yields of amide products in shorter reaction times under mild conditions at ambient temperature. Catalyst 4f is recyclable and promotes the formation of amides from aliphatic carboxylic acids and amines, and from heteroaromatic carboxylic acids and other functionalized substrates containing moieties like a free phenol, indole and pyridine. Mechanistic studies demonstrated the essential role of molecular sieves in this complex amidation process. The effect of substrate stoichiometry, concentration, and measurement of the catalyst order led to a possible catalytic cycle based on the presumed formation of an acylborate intermediate. The need for an electronically enriched ortho-iodo substituent in catalyst 4f supports a recent theoretical study (Marcelli, T. Angew. Chem. Int. Ed.2010, 49, 6840-6843) with a purported role for the iodide as a hydrogen-bond acceptor in the orthoaminal transition state.

Direct amidation of carboxylic acids catalyzed by ortho-iodo arylboronic acids: Catalyst optimization, scope, and preliminary mechanistic study supporting a peculiar halogen acceleration effect

The importance of amides as a component of biomolecules and synthetic products motivates the development of catalytic, direct amidation methods employing free carboxylic acids and amines that circumvent the need for stoichiometric activation or coupling reagents. ortho-Iodophenylboronic acid 4a has recently been shown to catalyze direct amidation reactions at room temperature in the presence of 4A molecular sieves as dehydrating agent. Herein, the arene core of ortho-iodoarylboronic acid catalysts has been optimized with regards to the electronic effects of ring substitution. Contrary to the expectation, it was found that electron-donating substituents are preferable, in particular, an alkoxy substituent positioned para to the iodide. The optimal new catalyst, 5-methoxy-2-iodophenylboronic acid (MIBA, 4f), was demonstrated to be kinetically more active than the parent des-methoxy catalyst 4a, providing higher yields of amide products in shorter reaction times under mild conditions at ambient temperature. Catalyst 4f is recyclable and promotes the formation of amides from aliphatic carboxylic acids and amines, and from heteroaromatic carboxylic acids and other functionalized substrates containing moieties like a free phenol, indole and pyridine. Mechanistic studies demonstrated the essential role of molecular sieves in this complex amidation process. The effect of substrate stoichiometry, concentration, and measurement of the catalyst order led to a possible catalytic cycle based on the presumed formation of an acylborate intermediate. The need for an electronically enriched ortho-iodo substituent in catalyst 4f supports a recent theoretical study (Marcelli, T. Angew. Chem. Int. Ed.2010, 49, 6840-6843) with a purported role for the iodide as a hydrogen-bond acceptor in the orthoaminal transition state.

BORONIC ACID CATALYSTS AND METHODS OF USE THEREOF FOR ACTIVATION AND TRANSFORMATION OF CARBOXYLIC ACIDS

The present application provides methods and catalysts for activation of carboxylic acids for organic reactions. In particular, methods are disclosed for direct nucleophilic addition reactions, such as, amidation reactions with amines, cycloadditions, and conjugate additions, using boronic acid catalysts of formula I, II or III: Also included are novel boronic acid catalysts of formula IV, V and III:

Structure-activity relationships and cancer-cell selective toxicity of novel inhibitors of glioma-associated oncogene homologue 1 (Gli1) mediated transcription

We report novel inhibitors of Gli1-mediated transcription as potential anticancer agents. Focused chemical libraries were designed and assessed for inhibition of functional cell-based Gli1-mediated transcription and selective toxicity toward cancer cells. The SAR was revealed, and the selectivity of the lead compounds' inhibition of Gli1-mediated transcription over that of Gli2 was determined. Compound 63 (NMDA298-1), which inhibited Gli1-mediated transcription in C3H10T1/2 cells with an IC50 of 6.9 μM, showed 3-fold selectivity for inhibiting transcription mediated by Gli1 over that by Gli2. Cell-viability assays were performed to evaluate the chemical library in a normal cell line and a panel of cancer cell lines with or without up-regulated expression of the Gli1 gene. These compounds decreased the viability of several cancer cell lines but were less active in the noncancerous BJ-hTERT cells. 2009 American Chemical Society.

PHENYL-CONTAINING N-ACYL AMINE AND AMINOACID DERIVATIVES, METHODS FOR THE PRODUCTION THEREOF, A PHARMACEUTICAL COMPOSITION AND THE USE THEREOF

The present invention relates to novel phenyl-N-acyl derivatives of biogenic amines and amino acids of general formula (I) as cyclooxynease inhibitors, possessing analgetic and anti-inflammatory properties and devoid of side effects in particular ulcerogeneity and pro-spasmodic actions, as well as capability to potentiate effect of other analgetics, and possessing in addition antihypoxic, antidepressant and anti-Parkinsonistic action; as well as to the processes for the preparation novel and known phenyl-N-acyl derivatives of biogenic amines, to a pharmaceutical composition and to an agent comprising compounds of general formula (I) as well as to use thereof and a method of treating.

Synthesis and identification of small molecules that potently induce apoptosis in melanoma cells through G1 cell cycle arrest

Late-stage malignant melanoma is a cancer that is refractory to current chemotherapeutic treatments. The average survival time for patients with such a diagnosis is 6 months. In general, the vast majority of anticancer drugs operate through induction of cell cycle arrest and cell death in either the DNA synthesis (S) or mitosis (M) phase of the cell cycle. Unfortunately, the same mechanisms that melanocytes possess to protect cells from DNA damage often confer resistance to drugs that derive their toxicity from S or M phase arrest. Described herein is the synthesis of a combinatorial library of potential proapoptotic agents and the subsequent identification of a class of small molecules (triphenylmethylamides, TPMAs) that arrest the growth of melanoma cells in the G1 phase of the cell cycle. Several of these TPMAs are quite potent inducers of apoptotic death in melanoma cell lines (IC50 ～ 0.5 μM), and importantly, some TPMAs are comparatively nontoxic to normal cells isolated from the bone marrow of healthy donors. Furthermore, the TPMAs were found to dramatically reduce the level of active nuclear factor κ-B (NFκB) in the cell; NFκB is known to be constitutively active in melanoma, and this activity is critical for the proliferation of melanoma cells and their evasion of apoptosis. Compounds that reduce the level of NFκB and arrest cells in the G1 phase of the cell cycle can provide insights into the biology of melanoma and may be effective antimelanoma agents.

3-Acyl-1,3-diaryltriazenes as neutral and selective acylating agents

New 3-acyl-1,3-diaryltriazenes have been prepared and their reactions with amino compounds have been studied. Reactions proceed rapidly under mild conditions to give the corresponding N-acyl products. Reagents enable chemoselective acylation of aliphatic primary and secondary amines in the presence of other acylable functional groups.

Iodonium ion-assisted synthesis of a tetrameric fragment corresponding to the cell wall phenolic glycolipids of Mycobacterium kansasii serovar I

Two procedures are described towards the assembly of the tyramine spacer-containing tetramer 5, a derivative of the phenolic glycolipid of Mycobacterium kansasii serovar I. First, iodonium ion-mediated glycosylation of trimeric acceptor 2a with D-rhamnopyranoside donor 10 gave fully protected tetramer 17. Selective removal of the chloroacetyl group of 17, subsequent deoxygenation and removal of the protective groups, led to target 5. The potential occurrence of double stereodifferentiation (DSD) was examined by condensation of L-fucopyranoside model acceptor 14 with both the enantiomeric rhamnopyranoside donors 10 and 13. The second procedure involves elongation of trimeric acceptor 2b with 6-deoxy-D-glucopyranoside 28. Desulfurisation of the resulting tetrameric fragment 36 followed by hydrogenation of 37 gave 38, the phenylacetyl (PhAc) of which was enzymatically removed to yield target tetramer 5.