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(65) Prior Publication Data Baldanzi et al. “Ghrelin and des-acyl Ghrelin Inhibit Cell Death in US 2007/OO21331 A1 Jan. 25, 2007 Cardiomyocytes and Endothelial Cells through ERK1/2 and Pl 3-kinase/AKT The Journal of Cell Biology 159(6): 1029-1037 Related U.S. Application Data (2002). Baldwin et al. “Symbiotic Approach to Drug Design: (63) Continuation-in-part of application No. 10/872,142, Antihypertensive f3-Adrenergic Blocking Agents' Journal of Medici filed on Jun. 18, 2004. nal Chemistry 22(11): 1284-1290 (1979). (60) Provisional application No. 60/642.271, filed on Jan. Banks et al. “Extent and Direction of Ghrelin Transport Across the 7, 2005, provisional application No. 60/622,055, filed Blood-Brain Barrier Is Determined by its Unique Primary Structure” on Oct. 27, 2004, provisional application No. 60/621, The Journal of Pharmacology and Experimental Therapeutics 302: 642, filed on Oct. 26, 2004, provisional application No. 822-827 (2002). 60/479,223, filed on Jun. 18, 2003. Barreiro et al. “Developmental, State-Specific, and Hormonally (51) Int. Cl. Regulated Expression of Growth Hormone Secretagogue Receptor A6 IK 38/12 (2006.01) Messenger RNA in Rat Testis' Biology of Reproduction 68: 1631 CO7K 5/12 (2006.01) 1640 (2002). (52) U.S. Cl. ........................................... 514/9; 530/317 (Continued) (58) Field of Classification Search ....................... None See application file for complete search history. Primary Examiner Andrew DKosar (56) References Cited (74) Attorney, Agent, or Firm Myers Bigel Sibley & U.S. PATENT DOCUMENTS Sajovec, PA 6,548,501 B2 4/2003 Hakkinen 6,586,403 B1* 7/2003 Mathison et al. .............. 514/18 (57) ABSTRACT 6,852,722 B2 2/2005 Hakkinen FOREIGN PATENT DOCUMENTS The present invention provides novel conformationally-de EP 1 159964 12/2001 fined macrocyclic compounds that have been demonstrated to WO WOO1/25257 4/2001 be selective modulators of the ghrelin receptor (growth hor WO WO 04/111077 12, 2004 mone secretagogue receptor, GHS-R1a and Subtypes, iso WO WO 05/O12331 2, 2005 forms and variants thereof). Methods of synthesizing the WO WO 05/O12332 2, 2005 novel compounds are also described herein. These com OTHER PUBLICATIONS pounds are useful as agonists of the ghrelin receptor and as medicaments for treatment and prevention of a range of medi W.-C. Qiu et al. J. Gastroenterol. (2008) 14(9), pp. 1419-1424.* J. Rudinger. 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