- Asymmetric alkylation of 5-alkyl-2-aminothiazolones using a C 2-symmetric chiral tetraamine base
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The diastereoselective alkylation of a series of 5-alkyl-2-aminothiazolones utilizing a C2-symmetric chiral tetraamine base is reported.
- Frizzle, Matthew J.,Nani, Roger R.,Martinelli, Michael J.,Moniz, George A.
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scheme or table
p. 5613 - 5616
(2011/11/12)
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- Discovery of a potent, orally active 11β-hydroxysteroid dehydrogenase type 1 inhibitor for clinical study: Identification of (S)-2-((1 S,2 S,4 R)-Bicyclo[2.2.1]heptan-2-ylamino)-5-isopropyl-5-methylthiazol-4(5 H)-one (AMG 221)
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Thiazolones with an exo-norbornylamine at the 2-position and an isopropyl group on the 5-position are potent 11β-HSD1 inhibitors. However, the C-5 center was prone to epimerization in vitro and in vivo, forming a less potent diastereomer. A methyl group was added to the C-5 position to eliminate epimerization, leading to the discovery of (S)-2-((1S,2S,4R)-bicyclo[2.2.1] heptan-2-ylamino)-5-isopropyl-5-methylthiazol-4(5H)-one (AMG 221). This compound decreased fed blood glucose and insulin levels and reduced body weight in diet-induced obesity mice.
- Véniant, Murielle M.,Hale, Clarence,Hungate, Randall W.,Gahm, Kyung,Emery, Maurice G.,Jona, Janan,Joseph, Smriti,Adams, Jeffrey,Hague, Andrew,Moniz, George,Zhang, Jiandong,Bartberger, Michael D.,Li, Vivian,Syed, Rashid,Jordan, Steven,Komorowski, Renée,Chen, Michelle M.,Cupples, Rod,Kim, Ki Won,St. Jean, David J.,Johansson, Lars,Henriksson, Martin A.,Williams, Meredith,Vallg?rda, Jerk,Fotsch, Christopher,Wang, Minghan
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supporting information; scheme or table
p. 4481 - 4487
(2010/09/04)
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- PROCESS FOR MAKING SUBSTITUTED 2-AMINO-THIAZOLONES
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The present invention relates to methods of making compounds that inhibit 11-β-hydroxysteroid dehydrogenase type 1 enzyme (11-β HSD1). One method comprises (a) contacting a compound of formula (II) with a chiral base, deprotonating agent, and an alkylating agent R3-LG, (b) contacting the product of (a) with an acid to form a salt, and (c) reacting the salt with a base to form the compound of formula (I); wherein Z, R1, R2, and R3 are defined herein.
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Page/Page column 43-44
(2010/04/03)
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- ASYMMETRIC PROCESS FOR MAKING SUBSTITUTED 2-AMINO-THIAZOLONES
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The invention provides two process for synthesizing substituted aminothiazolone compounds as inhibitors of 11-β-hydroxy steroid dehydrogenase type 1. The processes allow the stereoselective synthesis of the desired compounds without the use of stoichiometric amounts of chiral catalysts.
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Page/Page column 24-25
(2010/04/03)
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- Two asymmetric syntheses of AMG 221, an inhibitor of 11β- hydroxysteroid dehydrogenase type 1
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(Chemical Equation Presented) Two asymmetric syntheses of AMG 221 (2), an inhibitor of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) discovered in our laboratories, are reported. One of the syntheses utilizes chiral trimethylsilyl cyanohydrin 12 as s
- Caille, Seb,Cui, Sheng,Hwang, Tsang-Lin,Wang, Xiang,Faul, Margaret M.
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experimental part
p. 3833 - 3842
(2009/11/30)
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- PROCESS FOR MAKING SUBSTITUTED 2-AMINO-THIAZOLONES
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ABSTRACT The present invention relates to methods of making compounds that inhibit 11- -hydroxysteroid dehydrogenase type 1 enzyme (11- HSD1). One method comprises (a) contacting a compound of formula (II) sequentially with a chiral base in the presence o
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Page/Page column 47-48
(2009/03/07)
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