Dipeptide derivatives

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...

Reexamination Certificate

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Details

C514S214020, C514S250000, C514S290000, C514S292000, C514S411000, C540S558000, C540S559000, C540S561000, C540S586000, C544S344000, C546S079000, C546S084000, C546S101000, C548S427000

Reexamination Certificate

active

06953791

ABSTRACT:
This invention is directed to compounds of the formulaand the pharmaceutically-acceptable salts thereof, where the substituents are as defined in the Specification, which are growth hormone secretogogues and which increase the level of endogenous growth hormone. The compounds of this invention are useful for the treatment and prevention of osteoporosis and/or frailty, congestive heart failure, frailty associated with aging, obesity; accelerating bone fracture repair, attenuating protein catabolic response after a major operation, reducing cachexia and protein loss due to chronic illness, accelerating wound healing, or accelerating the recovery of burn patients or patients having undergone major surgery; improving muscle strength, mobility, maintenance of skin thickness, metabolic homeostasis or renal homeostasis. The compounds of the present invention are also useful in treating osteoporosis and/or frailty when used in combination with: a bisphosphonate compound such as alendronate; estrogen, premarin, and optionally progesterone; an estrogen agonist or antagonist; or calcitonin, and pharmaceutical compositions useful therefor. Further, the present invention is directed to pharmaceutical compositions useful for increasing the endogenous production or release of growth hormone in a human or other animal which comprises an effective amount of a compound of the present invention and a growth hormone secretagogue selected from GHRP-6, Hexarelin, GHRP-1, growth hormone releasing factor (GRF), IGF-1, IGF-2 or B-HT920. The invention is also directed to intermediates useful in the preparation of compounds of Formula I.

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Arvat, et al. “Arginine and Growth Hormone-Releasing Hormone Restore the Blunted Growth Hormone-Releasing Activity of Hexarelin in Elderly Subjects”,Journal of Clinical Endocrinology and Metabolism79(5), pp. 1440-1443 (1994).
Aloi, et al. “Neuroendocrine Responses to a Novel Growth Hormone Secretagogue, L-692,429, in Healthy Older Subjects”,Journal of Clinical Endocrinology and Metabolism79(4), pp. 943-949 (1994).
Gertz, et al. “L-692,429, a Nonpeptide Growth Hormone (GH) Secretagogue, Reverses Glucocorticoid Suppression of GH Secretion”,Journal of Clinical Endocrinology and Metabolism, 79 (3), pp. 745-749 (1994).
Jacks, et al. “Effects of acute and repeated intravenous administration of L-692,585, a novel non-peptidyl growth hormone secretagogue, on plasma growth hormone, IGF-1, ACTH, cortisol, prolactin, insulin, and thyroxine levels in beagles”Journal of Endocrinology143, pp. 399-406 (1994).
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