PROSTAGLANDIN E1 AND E2 ANALOGS FOR THE TREATMENT OF VARIOUS MEDICAL CONDITIONS
A prostaglandin analog with selectivity to EP receptors and demonstrating EP agonist activity that may be used to expand hematopoietic stem cell populations or to treat or prevent influenza, bone fracture, bone disease, glaucoma, ocular hypertension, dysmenorrhoea, pre-term labor, immune disorders, osteoporosis, asthma, allergy, male sexual dysfunction, female sexual dysfunction, periodontal disease, gastric ulcer, renal disease, or other EP receptor-mediated conditions.
1 . A compound of the general formula (I):
wherein dashed bonds may each independently represent a second carbon-carbon bond in order to give a carbon-carbon double bond with either (E) or (Z) geometry or may be ignored in order to give a carbon-carbon single bond;
wherein C 9 and C 11 each is independently C═CH 2 , C═O, CF 2 , CHF (any stereoisomer), or C(H)OH (any stereoisomer) with the proviso that C 9 does not equal C 11 , and also with the proviso that when one of either C 9 or C 11 is C═O, and the other is C(H)OH, at least one of Z 2 , Z 3 , Z 4 , and Z 5 is fluorine, and also with the proviso that when one of either C 9 or C 11 is CHF, the other is not C(H)OH;
wherein R 1 is CO 2 R 3 , CH 2 OR 3 , CONR 4 R 5 , COCH 2 OH, CONR 4 SO 2 R 5 , P(O)(OR 4 ) 2 , or
wherein R 3 is hydrogen or (C 1 -C 6 )-alkyl:
wherein R 4 and R 5 each is independently hydrogen or (C 1 -C 6 )-alkyl;
wherein Z 1 are hydrogen or fluorine;
wherein Z 2 and Z 3 each is independently hydrogen or fluorine;
wherein Z 4 and Z 5 each is independently hydrogen, fluorine, hydroxy, or methyl, or together are an oxygen atom that form a carbonyl group with the adjoining carbon atom of the ω chain; and
wherein Z 6 and Z 7 each is independently hydrogen, fluorine, hydroxy, or methyl, or together are an oxygen atom that form a carbonyl group with the adjoining carbon atom of the ω chain;
or any stereoisomer of the compound of the general formula (I), or any geometric isomer of the compound of the general formula (I), or an equivalent of the compound of the general formula (I), or a prodrug of the compound of the general formula (I), or a hydrate of the compound of the general formula (I), or a solvate of the compound of the general formula (I), or a pharmaceutically acceptable salt of the compound of the general formula (I).
2 . The compound of claim 1 , wherein the compound of the general formula (I) comprises the compound of general formula (II):
3 . The compound of claim 1 , wherein the compound of the general formula (I) comprises the compound of general formula (III):
4 . The compound of claim 1 , wherein the compound of the general formula (I) comprises the compound of general formula (IV):
5 . The compound of claim 1 , wherein the compound of the general formula (I) comprises the compound of general formula (V):
6 . A pharmaceutical composition comprising a pharmaceutically effective amount of a compound of claim 1 in admixture with a pharmaceutically acceptable carrier.
7 . A method of expanding hematopoietic stem cell populations in a culture or patient in need thereof comprising administering to the culture or the patient a compound according to claim 1 .
8 . A method of treatment for a patient comprising administering to the patient a compound according to claim 1 .
9 . The method of claim 8 , wherein said compound further comprises a pharmaceutically acceptable carrier.
10 . A method for treating or preventing EP receptor-mediated conditions in a subject, comprising the step of administering to the subject a compound according to claim 1 .