Synthesis and evaluation of the metabolites of AMG 221, a clinical candidate for the treatment of type 2 diabetes

ACS Medicinal Chemistry Letters

Volumn 2, Issue 11, 2011, Pages 824-827

  Li, Aiwen ^a   Yuan, Chester C ^a   Chow, David ^a   Chen, Michelle ^b   Emery, Maurice G ^a   Hale, Clarence ^b   Zhang, Xiping ^a   Subramanian, Raju ^a   St Jean, David J ^a   Komorowski, Renee ^b   Véniant, Murielle ^b   Wang, Minghan ^b   Fotsch, Christopher ^a  

^a AMGEN INC   (United States)

^b Department of Metabolic Disorders ^*  (United States)

Author keywords

11 HSD1 inhibitors; AMG 221; clinical candidate; metabolites

Indexed keywords

11BETA HYDROXYSTEROID DEHYDROGENASE 1; 2 (BICYCLO[2.2.1]HEPTAN 2 YLAMINO) 5 ISOPROPYL 5 METHYLTHIAZOL 4(5H) ONE; AMG 221; ANTIDIABETIC AGENT; DRUG METABOLITE; UNCLASSIFIED DRUG;

ADIPOSE TISSUE; ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DISTRIBUTION VOLUME; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG HALF LIFE; DRUG POTENCY; DRUG SCREENING; DRUG SYNTHESIS; ENZYME INHIBITION; IN VIVO STUDY; LIVER MICROSOME; MALE; MOUSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PRIORITY JOURNAL; RAT; STEREOCHEMISTRY;

RATTUS;

EID: 80955150846     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml2001467     Document Type: Article

References (11)

1. http://www.fda.gov/downloads/Drugs/ GuidanceComplianceRegulatoryInformation/Guidances/ucm079266.pdf.
2. Nedderman, A. N. R. Metabolites in safety testing: Metabolite identification strategies in discovery and development Biopharm. Drug Dispos. 2009, 30, 153-162
3. Fura, A. Role of pharmacologically active metabolites in drug discovery and development Drug Discovery Today 2006, 11, 133-142 (Pubitemid 43375964)
4. Fura, A.; Shu, Y.-Z.; Zhu, M.; Hanson, R. L.; Roongta, V.; Humphreys, W. G. Discovering Drugs through Biological Transformation: Role of Pharmacologically Active Metabolites in Drug Discovery J. Med. Chem. 2004, 47, 4339-4351 (Pubitemid 39096823)
5. Véniant, M. M.; Hale, C.; Hungate, R. W.; Gahm, K.; Emery, M. G.; Jona, J.; Joseph, S.; Adams, J.; Hague, A.; Moniz, G.; Zhang, J.; Bartberger, M. D.; Li, V.; Syed, R.; Jordan, S.; Komorowski, R.; Chen, M. M.; Cupples, R.; Kim, K. W.; St. Jean, D. J., Jr.; Johansson, L.; Henriksson, M. A.; Williams, M.; Vallgårda, J.; Fotsch, C.; Wang, M. 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) J. Med. Chem. 2010, 53, 4481-4487
6. Gibbs, J. P.; Emery, M. G.; McCaffery, I.; Smith, B.; Gibbs, M. A.; Akrami, A.; Rossi, J.; Paweletz, K.; Gastonguay, M. R.; Bautista, E.; Wang, M.; Perfetti, R.; Daniels, O. Population Pharmacokinetic/Pharmacodynamic Model of Subcutaneous Adipose 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1) Activity After Oral Administration of AMG 221, a Selective 11β-HSD1 Inhibitor J. Clin. Pharmacol. 2011, 51, 830-841
7. Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. A Chiral Chelating Diene as a New Type of Chiral Ligand for Transition Metal Catalysts: Its Preparation and Use for the Rhodium-Catalyzed Asymmetric 1,4-Addition J. Am. Chem. Soc. 2003, 125, 11508-11509 (Pubitemid 37213990)
8. Sen, S. E.; Roach, S. L. A Convenient Two-Step Procedure for the Synthesis of Substituted Allylic Amines from Allylic Alcohols Synthesis 1995, 756-758
9. Mayo, P.; Tam, W. Ring-opening metathesis"cross-metathesis reactions (ROM-CM) of substituted norbornadienes and norbornenes Tetrahedron 2002, 58, 9513-9525 (Pubitemid 35356441)
10. Moniz, G. A.; Frizzle, M. J.; Bernard, C.; Martinelli, M.; Faul, M.; Nani, R.; Larrow, J. Process for making 2-aminothiazolines. PCT Int. Appl. WO 2009002445 A1, 68 pp.
11. Kim, K.-Y.; Kim, B. C.; Lee, H. B.; Shin, H. Nucleophilic Fluorination of Triflates by Tetrabutylammonium Bifluoride J. Org. Chem. 2008, 73, 8106-8108