1110641-70-7

Upstream product

• 1110642-43-7 (S)-3-((S)-1-(4-bromophenyl)ethyl)-6-(2-oxopropyl)-6-phenyl-1,3-oxazinan-2-one 
• 75-16-1 methylmagnesium bromide 
• 1110641-69-4 (S)-3-[(S)-1-(4-bromo-phenyl)-ethyl]-6-(2-methyl-oxiranylmethyl)-6-phenyl-perhydro-1,3-oxazin-2-one 
• 1110642-44-8 3-((R)-3-((S)-1-(4-bromophenyl)ethyl)-2-oxo-6-phenyl-1,3-oxazinan-6-yl)propanal 
• 1383540-79-1 (S)-2-bromo-N-(1-(4-bromophenyl)ethyl)acetamide 
• 1383540-75-7 (R)-3-hydroxy-5-methyl-3-phenyl-5-(trimethylsilyloxy)hexanal 
• 1383540-73-5 phenyl (S)-1-(4-bromophenyl)ethyl((S)-3,5-dihydroxy-5-methyl-3-phenylhexyl)carbamate 
• 1383540-71-3 (R)-N-((S)-1-(4-bromophenyl)ethyl)-3,5-dihydroxy-5-methyl-3-phenylhexanamide 
• 144741-40-2 3-methyl-1-phenyl-3-(trimethylsilyloxy)butan-1-one 
• 43108-74-3 3-hydroxy-3-methyl-1-phenyl-1-butanone 
• 98-86-2 acetophenone 
• 143427-44-5 1-chloro-3-phenylhex-5-en-3-ol 
• 1110641-67-2 (R)-3-[(S)-1-(4-bromo-phenyl)-ethyl]-6-(2-methyl-allyl)-6-phenyl-perhydro-1,3-oxazin-2-one 
• 149552-52-3 (+)-(1S)-1-(4-bromophenyl)ethyl isocyanate 

Downstream Products

• 1110642-47-1 (S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborol-an-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one 
• 1237534-48-3 4-{(S)-1-[(S)-6-(2-hydroxy-2-methyl-propyl)-2-oxo-6-phenyl-[1,3]oxazinan-3-yl]-ethyl}-benzonitrile 
• 1259034-36-0 (S)-6-(2-hydroxy-2-methylpropyl)-3-((S)-1-(4-(3-hydroxy-3-methylbut-ynyl)phenyl)ethyl)-6-phenyl-1,3-oxazinan-2-one 
• 1259034-71-3 (S)-6-(2-hydroxy-2-methyl-propyl)-6-phenyl-3-[(S)-1-(4-trimethylsilylethynyl-phenyl)-ethyl]-[1,3]oxazinan-2-one 
• 1259034-67-7 (S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-((S)-1-(4-((triethylsilyl)ethynyl)phenyl)ethyl)-1,3-oxazinan-2-one 
• 1259034-68-8 (S)-3-((S)-1-(4-ethynylphenyl)ethyl)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one 
• 1259034-66-6 (S)-6-(2-hydroxy-2-methylpropyl)-3-((S)-1-(4-((2-methoxypyridin-4-yl)ethynyl)phenyl)ethyl)-6-phenyl-1,3-oxazinan-2-one 
• 1259034-70-2 (S)-6-(2-hydroxy-2-methyl-propyl)-3-{(S)-1-[4-(1-methyl-2-oxo-1,2-dihydro-pyridin-4-ylethynyl)-phenyl]-ethyl}-6-phenyl-[1,3]oxazinan-2-one 
• 1259034-39-3 4-(4-((S)-1-((S)-6-(2-hydroxy-2-methylpropyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)ethyl)phenyl)-2,2-dimethylbut-3-ynoic acid 
• 1259034-41-7 4-(4-((S)-1-((S)-6-(2-hydroxy-2-methylpropyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)ethyl)phenyl)-N,N,2,2-tetramethylbut-3-ynamide 
• 1259034-42-8 (S)-3-((S)-1-(4-(4-(azetidin-1-yl)-3,3-dimethyl-4-oxobut-1-ynyl)phenyl)ethyl)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one 
• 1259034-40-6 butyl 4-(4-((S)-1-((S)-6-(2-hydroxy-2-methylpropyl)-2-oxo-6-phenyl-1,3-oxazinan-3-yl)ethyl)phenyl)-2,2-dimethylbut-3-ynoate 
• 1114573-33-9 4-(4-{(S)-1-[(S)-6-(2-hydroxy-2-methylpropyl)-2-oxo-6-phenyl-[1,3]oxazinan-3-yl]ethyl}phenyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester 
• 1114573-37-3 3-[(S)-1-(4'-amino-3'-nitrobiphenyl-4-yl)ethyl]-(S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-[1,3]oxazinan-2-one 

Relevant academic research and scientific papers

Discovery of BI 135585, an in vivo efficacious oxazinanone-based 11β hydroxysteroid dehydrogenase type 1 inhibitor

A potent, in vivo efficacious 11β hydroxysteroid dehydrogenase type 1 (11β HSD1) inhibitor (11j) has been identified. Compound 11j inhibited 11β HSD1 activity in human adipocytes with an IC50 of 4.3?nM and in primary human adipose tissue with an IC80 of 53?nM. Oral administration of 11j to cynomolgus monkey inhibited 11β HSD1 activity in adipose tissue. Compound 11j exhibited >1000× selectivity over other hydroxysteroid dehydrogenases, displays desirable pharmacodynamic properties and entered human clinical trials in 2011.

METHODS OF MAKING DIASTEREOMERIC ORGANIC COMPOUNDS

Disclosed is a process for making diastereomeric compound of the formula (I): wherein m, n and R1 to R4 are as defined herein. The process of the invention provides the compound of formula (I) in high yield and substantially free of

INHIBITORS OF 11beta-HYDROXYSTEROID DEHYDROGENASE 1

This invention relates to novel compounds of the Formula (I), (Ia1-10), (Ib1-10), (Ic1-10), (Id1-7), (Ie1-5) pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful for the therapeutic treatment of diseases associated with the modulation or inhibition of 11β-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.

CYCLIC INHIBITORS OF 11BETA-HYDROXYSTEROID DEHYDROGENASE 1

This invention relates to novel compounds of the Formula (I), (II), (II-A), (Il-B), (ll-C), (ll-D), (III). (III-A). (IIIl-B). (IIl-C). (IIl-D), (III-E) (IV), (IV-A), (IV-B). (IV-C), (IV-D). (V), (V-A), (V-B), (V-C), (V-D), pharmaceutically acceptable salt

CYCLIC INHIBITORS OF 11 β-HYDROXYSTEROID DEHYDROGENASE 1

This invention relates to novel compounds of the Formula Formulas (I), (Ia1-20), (Ib1-20), (Ic1-20), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful for the therapeutic treatment of diseases associated with the modulation or inhibition of 11β-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.

CYCLIC INHIBITORS OF 11BETA-HYDROXYSTEROID DEHYDROGENASE 1

This invention relates to novel compounds of an 11 β-HSD1 inhibitor disclosed herein, pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful for the therapeutic treatment of diseases associated with the modula

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 11BETA-HYDROXYSTEROID DEHYDROGENASE 1

This invention relates to novel compounds of the Formula Ik, Im1, Im2, Im5, In1, In2, In5, Io1, Io2, Io5, Ip1, Ip3, pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful for the therapeutic treatment of diseases associated with the modulation or inhibition of 11β-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.