Claims for Patent: 6,362,231

Summary for Patent: 6,362,231

Title:	Calcium receptor active compounds
Abstract:	A novel calcium receptor active compound having the formula is provided: wherein: Ar.sub.1 is selected from the group consisting of aryl, heteroaryl, bis(arylmethyl)amino, bis(heteroarylmethyl)amino and arylmethyl(heteroarylmethyl)amino; X is selected from the group consisting of oxygen, sulfur, sulfinyl, sulfonyl, carbonyl and amino; R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8 and R.sup.9 are, for example, hydrogen or alkyl; Ar.sub.2 is selected from the group consisting of aryl and heteroaryl; p is an integer of from 0 to 6, inclusive; and, q is an integer of from 0 to 14, inclusive.
Inventor(s):	Sakai; Teruyuki (Gunma, JP), Takami; Atsuya (Gunma, JP), Nagao; Rika (Gunma, JP)
Assignee:	NPS Pharmaceuticals, Inc. (Salt Lake City, UT)
Application Number:	09/214,552
Patent Claims:	1. A compound having the formula: wherein: Ar.sub.1 is phenyl optionally substituted by one or more moieties independently selected from the group consisting of halogen, unsubstituted alkyl, lower alkyl substituted with one or more halogens, lower alkoxy optionally substituted with one or more halogens, and nitro; X is sulfur; q is an integer of from 0 to 14, inclusive; R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8 and R.sup.9 are independently hydrogen, or alkyl; and Ar.sub.2 is naphthyl optionally substituted by one or more medium alkyl moieties, or a pharmaceutically acceptable salt or hydrate of said compound. 2. The compound, salt or hydrate of claim 1, wherein: R.sup.5 is selected from the group consisting of hydrogen, and lower alkyl; and R.sup.6 and R.sup.7 are hydrogen. 3. The compound, salt or hydrate of claim 2 wherein R.sup.5 and R.sup.6 are hydrogen. 4. The compound, salt or hydrate of claim 3 wherein R.sup.3 and R.sup.4 are hydrogen. 5. The compound, salt or hydrate of claim 4 wherein R.sup.8 is hydrogen; and R.sup.9 is unsubstituted lower alkyl. 6. The compound, salt or hydrate of claim 5 wherein q is an integer of from 1 to 8, inclusive. 7. The compound, salt or hydrate of claim 6 wherein Ar2 is unsubstituted naphthyl. 8. The compound, salt or hydrate of claim 7 wherein R.sup.9 is methyl. 9. The compound, salt or hydrate of claim 8 wherein said compound is the R enantiomer. 10. The compound, salt or hydrate of claim 9 wherein s is an integer of from 1 to 5, inclusive. 11. A prodrug of said compound of claim 1. 12. The compound, salt or hydrate of claim 1 having the formula: ##STR1## 13. The compound, salt or hydrate of claim 1 wherein one of R8 or R9 is methyl. 14. The compound, salt or hydrate of claim 13 wherein said compound is the R enantiomer. 15. N-((1R)-(1-naphthyl)ethyl)-2-(2',5'-dichorophenylthio)ethylamine, N-((1R)-1-(1-napthyl)ethyl)-N-(5-{(4-(trifluoromethoxy)phenyl)thio}-pentyl )amine, N-((1R)-1-(1-naphthyl)ethyl)-N-(4-{(4-(trifluoromethoxy)phenyl)thio}-butyl )amine, N-{4-((2,4-dimethylphenyl)thio)butyl}-N-((1R)-1-(1-naphthyl)ethyl)amine, N-((1R)-1(1-naphthyl)ethyl)-N-(5-{(4-trifluoromethyl)phenyl)thio}-pentyl)a mine, N-((1R)-1-(1-naphthyl)ethyl)-N-{4-((2,4,5-trichlorophenyl)thio)butyl}amine , N-{5-((4-chlorophenyl)thio)pentyl}-N-((1R)-1-(1-naphthyl)ethyl)amine, N-{5((2,4-dimethylphenyl)thio)pentyl}-N-((1R)-1-(1-naphthyl)ethyl)amine, N-((1R)-1(1-naphthyl)ethyl)-N-(4-{(4-trifluoromethyl)phenyl)thio}butyl)ami ne, N-{4-((4-methylphenyl)thio)butyl}-N-((1R)-1-(1-naphthyl)ethyl)amine, N-{4((4-chlorophenyl)thio)butyl}-N-((1R)-1-(1-naphthyl)ethyl)amine, N-((1R)-1-(1-naphthyl)ethyl)-N-(6-{(4-(trifluoromethoxy)phenyl)thio}hexyl) amine, N-{5-((4-methoxyphenyl)thio)pentyl}-N-((1R)-1(1-naphthyl)ethyl)amine, N-((1R)-1-(1-naphthyl)ethyl)-N-{5-((2,4,5-tricholorophenyl)thio))pentyl}am ine, N-((1R)-1-(1-naphthyl)ethyl)-N-(4-{(2,3,5,6-tetrafluoro-4-(trifluoromethyl )phenyl)thio}butyl)amine, N-{5-((2,5-dichlorophenyl)thio)pentyl}-N-((1R)-1-(1-naphthyl)ethyl)amine, N-{5-((4-fluorophenyl)thio)pentyl}-N-((1R)-1-(1-naphthyl)ethyl)amine, N-{6-((4-chlorophenyl)thio)hexyl}-N-((1R)-1-(1-naphthyl)ethyl)amine, N-{4((3-methoxyphenyl)thio)butyl}-N-((1R)-1(1-naphthyl)ethyl)amine, N-{5-((4-methylphenyl)thio)pentyl}-N-((1R)-1-(1-naphthyl)ethyl)amine, N-{4-((2,5-dichlorophenyl)thio)butyl}-N-((1R)-1-(1-naphthyl)ethyl)amine, N-((1R)-1-(1-naphthyl)ethyl)-N-(5-{(2,3,5,6-tetrafluoro-4-(trifluoromethyl )phenyl)thio}pentyl)amine, N-((1R)-1-(1-naphthyl)ethyl)-N-(7-{(2,3,5,6-tetrafluoro-4-(trifluoromethyl )phenyl)thio}heptyl)amine, N-{(5-(3-methoxyphenyl)thio)pentyl}-N-((1R)-1-(1-naphthyl)ethyl)amine, N-((1R)-1-(1-naphthyl)ethyl)-N-(3-{(4-(trifluoromethyl)phenyl)thio}propyl) amine, N-((1R)-1-(1-naphthyl)ethyl)-N-(4-{(3-(trifluoromethyl)phenyl)thio}butyl)a mine, N-{4((4-fluorophenyl)thio)butyl}-N-((1R)-1-(1-naphthyl)ethyl)amine, or a salt or hydrate thereof. 16. A pharmaceutical composition comprising said compound, salt or hydrate of claim 1. 17. A method of treating a patient comprising administering to said patient a therapeutically effective amount of said compound, said salt, or said hydrate, of said claim 1. 18. The method of claim 17 wherein said patient is suffering from a disease or disorder characterized by either or both of (1) abnormal calcium homeostasis and, (2) an abnormal amount of an intracellular or extracellular messenger whose production can be affected by calcium receptor activity. 19. A method of modulating the PTH level in a patient comprising administering to said patient an effective amount of said compound, said salt, or said hydrate, of claim 1. 20. The method of claim 19 wherein said effective amount of said compound, said salt, or said hydrate, of claim 3 reduces said PTH level in said patient. 21. The method of claim 20 wherein said patient has an abnormally high PTH level and said effective amount of said compound, said salt, or said hydrate, of claim 1 reduces said PTH level in said patient to a degree sufficient to cause a decrease in plasma Ca2+. 22. The method of claim 20 wherein said patient has an abnormally high PTH level and said effective amount of said compound, said salt, or said hydrate, of claim 1 reduces said PTH level in said patient to a level present in a normal individual. 23. A method of modulating parathyroid hormone secretion in a patient comprising administering to said patient an effective amount of said compound, said salt, or said hydrate of claim 1. 24. The method of claim 23 wherein said effective amount of said compound, said salt, or said hydrate, of claim 1 reduces said parathyroid hormone secretion in said patient. 25. The method of claim 24 wherein said patient has an abnormally high parathyroid secretion and said effective amount of said compound, said salt, or said hydrate, of claim 1 reduces said parathyroid hormone secretion in said patient to a degree sufficient to cause a decrease on plasma Ca2+. 26. A method of modulating one or more Ca.sup.2+ receptors activities in a cell comprising administration of said compounds, said salt, or said hydrate of said claim 1 to said cell. 27. The method of claim 26 wherein said cell is a parathyroid cell, a juxtaglomerular kidney cell, a proximal tubule kidney cell, a parafollicular thyroid cell, a bone osteocast, a keratinocyte or a placental trophoblast. 28. A method for treating or preventing a disorder selected from the group consisting of hyperparathyroidism, renal osteodystrophy, hypercalcemia malignancy, osteoporosis, Paget's disease and hypertension comprising administering to a patient a therapeutically effective amount of said compound, said salt, or said hydrate, of claim 1. 29. The method of claim 28 wherein said patient suffers from primary hyperparathyroidism. 30. The method of claim 28 wherein said patient suffers from secondary hyperparathyroidism.

Details for Patent 6,362,231

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2016-07-08