193274-04-3Relevant academic research and scientific papers
Pyrazolinone-piperidine dipeptide growth hormone secretagogues (GHSs): Discovery of capromorelin
Carpino, Philip A.,Lefker, Bruce A.,Toler, Steven M.,Pan, Lydia C.,Hadcock, John R.,Cook, Ewell R.,DiBrino, Joseph N.,Campeta, Anthony M.,DeNinno, Shari L.,Chidsey-Frink, Kristin L.,Hada, William A.,Inthavongsay, John,Mangano, F. Michael,Mullins, Michelle A.,Nickerson, David F.,Ng, Oicheng,Pirie, Christine M.,Ragan, John A.,Rose, Colin R.,Tess, David A.,Wright, Ann S.,Yu, Li,Zawistoski, Michael P.,DaSilva-Jardine, Paul A.,Wilson, Theresa C.,Thompson, David D.
, p. 581 - 590 (2007/10/03)
Novel pyrazolinone-piperidine dipeptide derivatives were synthesized and evaluated as growth hormone secretagogues (GHSs). Two analogues, capromorelin (5, CP-424391-18, hGHS-R1a Ki=7 nM, rat pituicyte EC50=3 nM) and the des-methyl an
Discovery and biological characterization of capromorelin analogues with extended half-lives
Carpino, Philip A.,Lefker, Bruce A.,Toler, Steven M.,Pan, Lydia C.,Hadcock, John R.,Murray, Marianne C.,Cook, Ewell R.,DiBrino, Joseph N.,DeNinno, Shari L.,Chidsey-Frink, Kristin L.,Hada, William A.,Inthavongsay, John,Lewis, Sharon K.,Mangano,Mullins, Michelle A.,Nickerson, David F.,Ng, Oicheng,Pirie, Christine M.,Ragan, John A.,Rose, Colin R.,Tess, David A.,Wright, Ann S.,Yu, Li,Zawistoski, Michael P.,Pettersen, John C.,DaSilva-Jardine, Paul A.,Wilson, Theresa C.,Thompson, David D.
, p. 3279 - 3282 (2007/10/03)
New tert-butyl, picolyl and fluorinated analogues of capromorelin (3), a short-acting growth hormone secretagogue (GHS), were prepared as part of a program to identify long-acting GHSs that increase 24-h plasma IGF-1 levels. Compounds 4c and 4d (ACD LogD values ≥2.9) displayed extended plasma elimination half-lives in dogs, primarily due to high volumes of distribution, but showed weak GH secretagogue activities in rats (ED50s>10 mg/kg). A less lipophilic derivative 4 (ACD LogD=1.6) exhibited a shorter canine half-life, but stimulated GH secretion in two animal species. Repeat oral dosing of 4 in dogs for 29 days (6 mg/kg) resulted in a significant down-regulation of the post dose GH response and a 60 and 40% increase in IGF-1 levels relative to pre-dose levels at the 8- and 24-h post dose time points. Compound 4 (CP-464709-18) has been selected as a development candidate for the treatment of frailty.
Treatment of insulin resistance with growth hormone secretagogues
-
, (2008/06/13)
This invention is directed to methods of treating insulin resistance in a mammal which comprise administering an effective amount of a compound of formula I, where the variables are defined in the specification, or the stereoisomeric mixtures, diastereomerically enriched, diastereomerically pure, enantiomerically enriched or enantiomerically pure isomers, or the pharmaceutically acceptable salts and prodrugs thereof to said mammal. The compounds of formula I are growth hormone secretagogues and as such are useful for increasing the level of endogenous growth hormone. In another aspect this invention provides certain intermediates which are useful in the synthesis of the foregoing compounds and certain processes useful for the synthesis of said intermediates and the compounds of formula I. This invention is further directed to methods comprising administering to a human or other animal a combination of a functional somatostatin antagonist such as an alpha-2 adrenergic agonist and a compound of formula I.
