Tetrahydroquinoline sulfonamides as γ-secretase inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 17, Issue 1, 2007, Pages 205-207

  Asberom, Theodros ^a   Bara, Thomas A ^a   Clader, John W ^a   Greenlee, William J ^a   Guzik, Henry S ^a   Josien, Hubert B ^a   Li, Wei ^a   Parker, Eric M ^a   Pissarnitski, Dmitri A ^a   Song, Lixin ^a   Zhang, Lili ^a   Zhao, Zhiqiang ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

secretase inhibitors; Alzheimer's disease; Sulfonamides

Indexed keywords

GAMMA SECRETASE INHIBITOR; QUINALDIC ACID; QUINOLINE DERIVATIVE; SULFONAMIDE;

ALZHEIMER DISEASE; ARTICLE; DEPROTECTION REACTION; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; ESTERIFICATION; STRUCTURE ACTIVITY RELATION;

ALZHEIMER DISEASE; AMYLOID PRECURSOR PROTEIN SECRETASES; HUMANS; PROTEASE INHIBITORS; QUINOLINES; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONAMIDES;

EID: 33845648831     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.09.064     Document Type: Article

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7. Preliminary SAR studies carried out on the perhydroquinoline lead series 1 established sulfonamide as optimum substituent on the ring nitrogen (unpublished result).
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9. 50 data shown are average of minimum of three independent results.
10. The two enantiomers of 8 (X = H) were separated by preparative HPLC. The following conditions were used for AS Chiralpack column: hexane/isopropanol, 90/10, 45 mL/min, 254 nM, 117.41 min (isomer A), 256.51 min (isomer B). Each enantiomer was independently converted to the enantiomerically pure carbamate.
11. The compounds listed in Table 3 were prepared in analogous fashion to the compounds listed in Table 1. The requisite fluorinated 2-methyl Quinoline starting materials were prepared using Doebner-Miller quinoline synthesis as modified by. Matsugi M., Tabusa F., and Minimikawa J. Tetrahedron Lett. (2000) 8523
12. Pissarnitski, V. A.; Asberom, T.; Bara, A. T.; Buevich, V. A.; Clader, W. J.; Greenlee, J. W.; Guzik, S. H.; Josien, B. H.; Li, W.; McEwan, M.; McKittrick, A. B.; Nechuta, L. T.; Nomeir, A. A.; Sinning, L.; Smith, M. E.; Parker, M. E.; Vaccaro, A. H.; Voight, H. J.; Zhang, L.; Zhao, Z.; Bioorg. Med. Chem. Lett. in press.