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Biotech / Medical : Gliatech (GLIA) -- Ignore unavailable to you. Want to Upgrade?

To: scaram(o)uche who wrote (691)	3/26/1999 12:40:00 AM
From: scaram(o)uche	Respond to of 2001

J Med Chem 1999 Mar 11;42(5):903-909 Design, Synthesis, and Structure-Activity Relationships of Acetylene-Based Histamine H3 Receptor Antagonists. Ali SM, Tedford CE, Gregory R, Handley MK, Yates SL, Hirth WW, Phillips JG Gliatech Inc., 23420 Commerce Park Road, Cleveland, Ohio 44122. [Record supplied by publisher] New, potent, and selective histamine H3 receptor antagonists have been synthesized by employing the use of (1) an appropriately positioned nonpolar acetylene spacer group, (2) either a two-carbon straight chain linker or a conformationally restricting trans-cyclopropane ring between the C-4 position of an imidazole headgroup and the acetylene spacer, and (3) a Topliss operational scheme for side-chain substitution for optimizing the hydrophobic domain. Compounds 9-18 are examples synthesized with the two-carbon straight chain linker, whereas 26-31 are analogues prepared by incorporation of the trans-(+/-)-cyclopropane at the C-4 position of an imidazole headgroup. Synthesis of both the (1R,2R)- and (1S,2S)-cyclopropyl enantiomers of the most potent racemic compound 31 (Ki = 0.33 +/- 0.13 nM) demonstrated a stereopreference in H3 receptor binding affinity for the (1R,2R) enantiomer 32 (Ki = 0.18 +/- 0.04 nM) versus the (1S,2S) enantiomer 33 (Ki = 5.3 +/- 0.5 nM). (1R,2R)-4-(2-(5,5-Dimethylhex-1-ynyl)cyclopropyl)imidazole (32) is one of the most potent histamine H3 receptor antagonists reported to date.

To: scaram(o)uche who wrote (691)	3/26/1999 12:43:00 AM
From: scaram(o)uche	Read Replies (1) \| Respond to of 2001

Title: DERIVATIVES OF 1-((3,3-DIMETHYL-3-SILABUTOXY)METHYL)-2-(PHENYLSULFONYL)IMIDAZOLE Publication date: 1999-02-11 Inventor(s): PHILLIPS JAMES G (US) Applicant(s): GLIATECH INC (US); PHILLIPS JAMES G (US) Requested Patent: WO9906377 A 19990211 Application Number: WO1998US15127 19980722 Priority Number(s): US19970055077P 19970801 IPC Classification: C07D233/54