7133-68-8

Upstream product

• 77-83-8 fraeseol 
• 84736-61-8 (+/-)-(3-hydroxy-3-phenyl-butyl)-acetate 
• 98-83-9 isopropenylbenzene 
• 2293-60-9 ethyl 3-hydroxy-3-phenylbutyrate 
• 4743-74-2 2-phenylpent-4-en-2-ol 
• 3759-31-7 3-hydroxy-3-phenylbutanoic acid 
• 108-86-1 bromobenzene 
• 590-90-9 1-Hydroxy-3-butanone 
• 100-58-3 phenylmagnesium bromide 
• 98-86-2 acetophenone 
• 120586-00-7 3-hydroxy-3-phenyl-butyraldehyde 

Downstream Products

• 7306-12-9 1-acetoxy-3-phenyl-but-3-ene 
• 6337-27-5 (+/-)-4-phenyl-cyclohex-4-ene-1r,2c-dicarboxylic acid-anhydride 
• 2288-18-8 2-phenyl-1,3-butadiene 
• 1260136-99-9 4-methyl-1,3-dioxa-4-phenyl-2-sila-2,2-bis(3,5-xylyl)cyclohexane 
• 1260137-01-6 2,2-di-tert-butyl-4-methyl-1,3-dioxa-4-phenyl-2-silacyclohexane 
• 1260137-02-7 1-di-tert-butylsilyloxy-3-phenylbutan-3-ol 
• 1260136-94-4 1,3-dioxa-4-methyl-2,2,4-triphenyl-2-silacyclohexane 
• 1260136-98-8 2,2-bis(4-anisyl)-4-methyl-1,3-dioxa-4-phenyl-2-silacyclohexane 
• 1260137-00-5 4-methyl-1,3-dioxa-4-phenyl-2-sila-2,2-bis(2-tolyl)cyclohexane 
• 1388181-58-5 (+/-)-4-methyl-4-phenyl-1,3-dioxan-2-one 
• 19352-16-0 (+/-)-4-chloro-2-phenylbutan-2-ol 
• 52553-03-4 5-methyl-5-phenyloxazolidin-2-one 
• 1114063-89-6 3-(2',4'-difluorobiphenyl-3-yl)-6-methyl-6-phenyl-1,3-oxazinan-2-one 
• 1114573-85-1 (6S)-3-(4'-fluorobiphenyl-3-yl)-6-methyl-6-phenyl-1,3-oxazinan-2-one 

Relevant academic research and scientific papers

Resolution of diols via catalytic asymmetric acetalization

A highly enantioselective kinetic resolution of diols via asymmetric acetalization has been achieved using a chiral confined imidodiphosphoric acid catalyst. The reaction is highly efficient for the resolution of tertiary alcohols, giving selectivity factors of up to >300. Remarkably, even in cases where the selectivity factors are only moderate, highly enantioenriched diols are obtained via a stereodivergent resolution to diastereomeric acetals.

Synthesis of oxazolidin-2-ones and imidazolidin-2-ones directly from 1,3-diols or 3-amino alcohols using iodobenzene dichloride and sodium azide

A general and efficient method for the synthesis of oxazolidin-2-ones and imidazolidin-2-ones directly from 1,3-diols and 3-amino alcohols has been developed using the same reagent combination of iodobenzene dichloride (PhICl2) and sodium azide (NaN3).

Structure-based design and synthesis of 1,3-oxazinan-2-one inhibitors of 11β-hydroxysteroid dehydrogenase type 1

Structure based design led directly to 1,3-oxazinan-2-one 9a with an IC50 of 42 nM against 11β-HSD1 in vitro. Optimization of 9a for improved in vitro enzymatic and cellular potency afforded 25f with IC 50 values of 0.8 nM for the enzyme and 2.5 nM in adipocytes. In addition, 25f has 94% oral bioavailability in rat and >1000× selectivity over 11β-HSD2. In mice, 25f was distributed to the target tissues, liver, and adipose, and in cynomolgus monkeys a 10 mg/kg oral dose reduced cortisol production by 85% following a cortisone challenge.

Base-catalyzed dehydrogenative Si-o coupling of dihydrosilanes: Silylene protection of diols

The direct dehydrogenative coupling of 1,3- and 1,4-diols and dihydrosilanes is efficiently catalyzed by CsO(10 mol%), cleanly affording six- and seven-membered 1,3-dioxo-2-silacycles with dihydrogen as the sole by-product. Conversely, 1,2-diols do not yield the expected 1,3-dioxo-2- silacyclopentanes, essentially forming cyclic disiloxanes instead. Aside from the synthetic convenience, the procedure itself is also useful for straight-forward diol derivatization prior to GLC analysis. Georg Thieme Verlag Stuttgart · New York.

SYNTHESIS OF INHIBITORS OF 11BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1

Disclosed are syntheses of 11 beta-HSD1 inhibitors and corresponding intermediates that are promising for the treatment of a variety of disease states including diabetes, metabolic syndrome, obesity, glucose intolerance, insulin resistance, hyperglycemia, hypertension, hypertension-related cardiovascular disorders, hyperlipidemia, deleterious gluco-corticold effects on neuronal function (e.g. cognitive impairment, dementia, and/or depression), elevated intra-ocular pressure, various forms of bone disease (e.g., osteoporosis), tuberculosis, leprosy (Hansen's disease), psoriasis, and impaired wound healing (e.g., in patients that exhibit impaired glucose tolerance and/or type 2 diabetes).

CYCLIC INHIBITORS OF 11β-HYDROXYSTERIOD DEHYDROGENASE 1

This invention relates to novel compounds of the Formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), (Ig), (Ih); (Ii); (Ij), (Ik), (II) pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful for the therapeutic treatment of diseases associated with the modulation or inhibition of 11 β-HSD1 in mammals. The invention further relates to pharmaceutical compositions of the novel compounds and methods for their use in the reduction or control of the production of cortisol in a cell or the inhibition of the conversion of cortisone to cortisol in a cell.