81228-03-7

Upstream product

• 22096-25-9 sodium phenethylate 
• 79-11-8 chloroacetic acid 
• 60-12-8 2-phenylethanol 
• 3926-62-3 sodium monochloroacetic acid 
• 1046818-42-1 tert-butyl 2-phenethoxyacetate 
• 3587-61-9 1-chloromethyl 2-phenylethyl ether 
• 68060-31-1 phenethyloxy-acetonitrile 

Downstream Products

• 74121-91-8 (2-Hydroxyethyl)phenylethyl ether 
• 948893-87-6 1-phenethyloxy-2-(toluene-4-sulfonyloxy)-ethane 
• 90875-77-7 2-phenethyloxyethylchloride 
• 948894-28-8 8-(benzyloxy)-5-{(1R)-1-{[tert-butyl(dimethyl)silyl]oxy}-2-[({4-methyl-1-[2-(2-phenylethoxy)ethyl]piperidin-4-yl}methyl)amino]ethyl}quinolin-2(1H)-one 
• 948895-16-7 8-(benzyloxy)-5-{(1R)-1-hydroxy-2-[({4-(hydroxymethyl)-1-[2-(2-phenylethoxy)ethyl]piperidin-4-yl}methyl)amino]ethyl}quinolin-2(1H)-one 
• 948893-93-4 5-{(1R)-1-{[tert-butyl(dimethyl)silyl]oxy}-2-[({4-hydroxy-1-[2-(2-phenylethoxy)ethyl]piperidin-4-yl}methyl)amino]ethyl}-8-hydroxyquinolin-2(1H)-one 
• 948894-20-0 5-{(1R)-1-{[tert-butyl(dimethyl)silyl]oxy}-2-[({(3R)-1-[2-(2-phenylethoxy)ethyl]piperidin-3-yl}methyl)amino]ethyl}-8-hydroxyquinolin-2(1H)-one 
• 948894-30-2 8-(benzyloxy)-5-{(1R)-1-hydroxy-2-[({4-methyl-1-[2-(2-phenylethoxy)ethyl]piperidin-4-yl}methyl)amino]ethyl}quinolin-2(1H)-one 
• 948893-89-8 5-[(R)-1-{[tert-butyl(dimethyl)silyl]oxy}-2-({1-[2-(2-phenylethoxy)ethyl]piperidin-4-yl}amino)ethyl]-8-hydroxyquinolin-2(1H)-one 
• 948895-12-3 methyl 4-(azidomethyl)-1-[2-(2-phenylethoxy)ethyl]piperidine-4-carboxylate 
• 948894-17-5 (3S)-1-(2-phenethyloxy-acetyl)-piperidine-3-carboxylic acid ethyl ester 
• 948895-13-4 {4-(aminomethyl)-1-[2-(2-phenylethoxy)ethyl]piperidin-4-yl}methanol 
• 948894-38-0 4-(azidomethyl)-1-[2-(2-phenylethoxy)ethyl]piperidin-4-ol 
• 948894-49-3 1-[4-(2-hydroxy-ethyl)-piperidin-1-yl]-2-phenethyloxy-ethanone 

Relevant academic research and scientific papers

The Methylene Alkoxy Carbamate Self-Immolative Unit: Utilization for the Targeted Delivery of Alcohol-Containing Payloads with Antibody–Drug Conjugates

A strategy for the conjugation of alcohol-containing payloads to antibodies has been developed and involves the methylene alkoxy carbamate (MAC) self-immolative unit. A series of MAC β-glucuronide model constructs were prepared to evaluate stability and enzymatic release, and the results demonstrated high stability at physiological pH in a substitution-dependent manner. All the MAC model compounds efficiently released alcohol drug surrogates under the action of β-glucuronidase. To assess the MAC technology for ADCs, the potent microtubule-disrupting agent auristatin E (AE) was incorporated through the norephedrine alcohol. Conjugation of the MAC β-glucuronide AE drug linker to the anti-CD30 antibody cAC10, and an IgG control antibody, gave potent and immunologically specific activities in vitro and in vivo. These studies validate the MAC self-immolative unit for alcohol-containing payloads within ADCs, a class that has not been widely exploited.

Disubstituted beta-lactones as inhibitors of N-acylethanolamine acid amidase (NAAA)

The present invention provides compounds and pharmaceutical compositions for inhibiting N-acylethanolamine acid amidase (NAAA). Inhibition of NAAA is contemplated as a method to sustain the levels of palmitoylethanolamide (PEA) and oleylethanolamide (OEA), two substrates of NAAA, in conditions characterized by reduced concentrations of PEA and OEA. The invention also provides methods for treating inflammatory diseases and pain, and other disorders in which decreased levels of PEA and OEA are associated with the disorder.

Synthesis and structure-activity relationship (SAR) of 2-methyl-4-oxo-3- oxetanylcarbamic acid esters, a class of potent N-acylethanolamine acid amidase (NAAA) inhibitors

N-Acylethanolamine acid amidase (NAAA) is a lysosomal cysteine hydrolase involved in the degradation of saturated and monounsaturated fatty acid ethanolamides (FAEs), a family of endogenous lipid agonists of peroxisome proliferator-activated receptor-α, which include oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). The β-lactone derivatives (S)-N-(2-oxo-3-oxetanyl)-3-phenylpropionamide (2) and (S)-N-(2-oxo-3-oxetanyl)- biphenyl-4-carboxamide (3) inhibit NAAA, prevent FAE hydrolysis in activated inflammatory cells, and reduce tissue reactions to pro-inflammatory stimuli. Recently, our group disclosed ARN077 (4), a potent NAAA inhibitor that is active in vivo by topical administration in rodent models of hyperalgesia and allodynia. In the present study, we investigated the structure-activity relationship (SAR) of threonine-derived β-lactone analogues of compound 4. The main results of this work were an enhancement of the inhibitory potency of β-lactone carbamate derivatives for NAAA and the identification of (4-phenylphenyl)-methyl-N-[(2S,3R)-2-methyl-4-oxo-oxetan-3-yl]carbamate (14q) as the first single-digit nanomolar inhibitor of intracellular NAAA activity (IC50 = 7 nM on both rat NAAA and human NAAA).

DISUBSTITUTED BETA-LACTONES AS INHIBITORS OF N-ACYLETHANOLAMINE ACID AMIDASE (NAAA)

The present invention provides compounds and pharmaceutical compositions for inhibiting N-acylethanolamine acid amidase (NAAA). Inhibition of NAAA is contemplated as a method to sustain the levels of palmitoylethanolamide (PEA) and oleylethanolamide (OEA), two substrates of NAAA, in conditions characterized by reduced concentrations of PEA and OEA. The invention also provides methods for treating inflammatory diseases and pain, and other disorders in which decreased levels of PEA and OEA are associated with the disorder.

Pyrido pyrimidinones as selective agonists of the high affinity niacin receptor GPR109A: Optimization of in vitro activity

Pyrido pyrimidinones are selective agonists of the human high affinity niacin receptor GPR109A (HM74A). They show no activity on the highly homologous low affinity receptor GPR109B (HM74). Starting from a high throughput screening hit the in vitro activity of the pyrido pyrimidinones was significantly improved providing lead compounds suitable for further optimization.

Practical preparation of benzyloxyacetic acids

An efficient and practical method for the preparation of benzyloxyacetic acids is described. The procedure involves the reaction of readily available chloroacetic acid with benzyl alcohol in the presence of powdered KOH providing a safer alternative to the known literature procedures, which completely eliminates the use of pyrophoric bases such as sodium hydride and sodium metal.

Novel pyridopyprimidinone derivatives which are HM74A agonists

The invention is concerned with novel pyridopyrimidinone derivatives of formula (I): wherein R1 to R8, X, Y, m and n are as defined in the description and in the claims. The compounds of the present invention are HM74A agonists with

PHENETHANOLAMINE DERIVATIVES AS BETA2 ADRENORECEPTOR AGONISTS

The present invention relates to compounds according to formula (I), a process for preparing them, the intermediate compounds of the process and the use of the compounds in the manufacture of a medicament for use in treating diseases such as ARDS, pulmonary emphysema, bronchitis, bronchiectasis, COPD, asthma and rhinitis. The compounds are beta2 adrenoreceptor agonists.

DIALKYL ETHER DELIVERY AGENTS

The present invention provides dialkyl ether compounds and pharmaceutically acceptable salts thereof, compositions containing the same and one or more active agents, and methods of administering active agents with the same.

SUBSTITUTED PHENOXY-AMINOPROPANOLS

Substituted phenoxy-aminopropanols of the formula STR1 wherein R is a branched-chain alkyl of 3 or 4 carbon atoms, R 1 is hydrogen, halogen or lower alkyl and R 2 and R 3, independently, are hydrogen, halogen, lower alkyl, lower alkoxy or lower alkylthio, and pharmaceutically acceptable acid addition salts thereof, are described. A process for their preparation, as well as pharmaceutical preparations containing them are also described. The compounds of formula I and their salts possess cardioselective β-adrenergic blocking activity and antihypertensive activity.