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US 6,211,244 B1Granted
Calcium receptor-active compounds
AssigneeNPS Pharmaceuticals, Inc.
InventorsBradford C. Van Wagenen, Scott T. Moe, Manuel F. Balandrin, Eric G. DelMar, Edward F. Nemeth
Life of this patent
Estimating the term…
Abstract
The present invention features compounds able to modulate one or more activities of an inorganic ion receptor and methods for treating diseases or disorders by modulating inorganic ion receptor activity. Preferably, the compound can mimic or block the effect of extracellular Ca2+ on a calcium receptor.
Claims46
A compound having the formula:
- wherein Ar5 is either naphthyl or phenyl optionally substituted with 0 to 5 substituents each independently selected from the group consisting of, lower alkyl, halogen, lower alkoxy, lower thioalkyl, methylene dioxy, lower haloalkyl, lower haloalkoxy, OH, CH2OH, CONH2, CN, acetoxy, benzyl, benzyloxy, α,α-dimethylbenzyl, NO2, CHO, CH3CH(OH), acetyl, ethylene dioxy, and —CH═CH-phenyl;
- Ar6 is phenyl substituted with 1 to 5 substituents each independently selected from the group consisting of acetyl, lower alkyl, halogen, lower alkoxy, lower thioalkyl, methylene dioxy, lower haloalkyl, lower haloalkoxy, OH, CH2OH, CONH2, CN, carbomethoxy, OCH2C(O)C2H5 and OCH2C(O)OC2H5 and acetoxy, provided that at least one substituent is OCH2C(O)OC2H5;
- R11 is hydrogen or methyl;
- and
- R12 is hydrogen or methyl;
- provided that at least one of R11 and R12 is methyl;
- or a pharmaceutically acceptable salt or complex thereof.
4 more elements
A compound selected from the group consisting of:
- 21S ((R)-N-(3-(2-chlorophenyl)propyl)-1-(3-propoxyphenyl)ethylamine);
- 21T ((R)-N-(3-(2-chlorophenyl)propyl)-1-(3-isopropoxyphenyl)ethylamine);
- 21U ((R)-N-(3-(2-chlorophenyl)propyl)-1-(3-isobutoxyphenyl)ethylamine):
- 21Y ((R,R)-N-(4-(3-(trifluoromethyl)phenyl)-2-butyl)-1-(3-methoxyphenyl)ethylamine);
- 22J ((R)-N-(3-(3-(trifluoromethyl)phenyl)propyl)-1-(1-naphthyl)ethylamine);
- 23A ((R)-N-(4-(3-(trifluoromethoxy)phenyl)-2-butyl)-1-(3-methoxyphenyl)ethylamine):
- 23E ((R)-N-((3-(trifluoromethoxy)phenyl)methyl)-1-(1-naphthyl)ethylamine;
- 24B (N-((3-methyl-4-methoxyohenyl)methyl)-1(2-(trifluoromethyl)phenyl)ethylamine);
- 24J ((R)-N-(3-(3-(trifluoromethoxy)phenyl)proyl)-1-(1-naphthyl)ethylamine;
- 24M ((R)-N-(3-(3,5-difluorophenyl)propyl)-1-(3-methoxyphenyl)ethylamine;
- 24V (N-((3-methyl-4-methoxyphenyl)methyl)-1-(3-(ethylacetoxy)phenyl)ethylamine);
- 24X ((R)-N-((3-bromo-4-methoxyphenyl)methyl)-1-(1-naphthyl)ethylamine);
- 24Y ((R)-N-((3-chloro-4-ethoxyphenyl)methyl)-1-(1-naphthyl)ethylamine;
- 25C ((S,R)-N-(4-(3-trifluoromethyl)phenyl)-2-butyl)-1-(1-naphthyl)ethylamine);
- 25D ((R,R)-N-(4-(3-trifluoromethyl)phenyl)-2-butyl)-1-(1-naphthyl)ethylamine);
- and
- 25E ((R)-N-(3-phenylprop-2-en-1-yl)-1-(3-methoxyphenyl)ethylamine:
- or a pharmaceutically acceptable salt or complex thereof.
15 more elements
A method of inhibiting bone resorption in a patient comprising the step of administering to said patient a therapeutically effective amount of a compound selected from the group consisting of:
- 21S ((R)-N-(3-(2-chlorophenyl)propyl)-1-(3-propoxyphenyl)ethylamine);
- 21T ((R)-N-(3-(2-chlorophenyl)propyl)-1-(3-isopropoxyphenyl)ethylamine);
- 21U ((R)-N-(3-(2-chlorophenyl)propyl)-1-(3-isobutoxyphenyl)ethylamine);
- 21Y ((R,R)-N-(4-(3-(trifluoromethyl)phenyl)-2-butyl)-1-(3-methoxyphenyl)ethylamine);
- 22J ((R)-N-(3-(3-(trifluoromethyl)phenyl)propyl)-1-(1-naphthyl)ethylamine);
- 23A ((R)-N-(4-(3-(trifluoromethoxy)phenyl)-2-butyl)-1-(3-methoxyphenyl)ethylamine);
- 23E ((R)-N-((3-(trifluoromethoxy)phenyl)methyl)-1-(1-naphthyl)ethylamine;
- 24B (N-((3-methyl-4-methoxyphenyl)methyl)-1-(2-(trifluoromethyl)phenyl)ethylamine);
- 24J ((R)-N-(3-(3-(trifluoromethoxy)phenyl)propyl)-1-(1-naphthyl)ethylamine;
- 24M ((R)-N-(3-(3,5-difluorophenyl)propyl)-1-(3-methoxyphenyl)ethylamine;
- 24V (N-((3-methyl-4-methoxyphenyl)methyl)-1-(3-(ethylacetoxy)phenyl)ethylamine);
- 24X ((R)-N-((3-bromo-4-methoxyphenyl)methyl)-1-(1-naphthyl)ethylamine);
- 24Y ((R)-N-((3-chloro-4-ethoxyphenyl)methyl)-1-(1-naphthyl)ethylamine;
- 25C ((S,R)-N-(4-(3-trifluoromethyl)phenyl)-2-butyl)-1-(1-naphthyl)ethylamine);
- 25D ((R,R)-N-(4-(3-trifluoromethyl)phenyl)-2-butyl)-1-(1-naphthyl)ethylamine);
- and
- 25E ((R)-N-(3-phenylprop-2-en-1-yl)-1-(3-methoxyphenyl)ethylamine;
- or a pharmaceutically acceptable salt or complex thereof.
15 more elements
A compound having the formula:
- wherein Ar3 is either naphthyl or phenyl optionally substituted with 0 to 5 substituents each independently selected from the group consisting of, lower alkyl, halogen, lower alkoxy, lower thioalkyl, methylene dioxy, lower haloalkyl, lower haloalkoxy, OH, CH2OH, CONH2, CN, acetoxy, benzyl, benzyloxy, dimethylbenzyl, NO2, CHO, CH3CH(OH), N(CH3)2, acetyl, and ethylene dioxy;
- Ar4 is either naphthyl or phenyl optionally substituted with 0 to 5 substituents each independently selected from the group consisting of lower alkyl, halogen, lower alkoxy, lower thioalkyl, methylene dioxy, lower haloalkyl, lower haloalkoxy, OH, CH2OH, CONH2, CN, and acetoxy;
- provided that if Ar4 is 3-methoxyphenyl, then Ar3 is a substituted phenyl that is not 2-methoxy, 3-methyl, 2-methyl, 4-methyl, 2,4-dimethyl, 2,4,6-trimethyl, or 4-isopropyl;
- and if Ar4 is unsubstituted phenyl, then Ar3 is a substituted phenyl that is not 2-nitrophenyl, 4-nitrophenyl, or 4-dimethylaminophenyl;
- R8 is either hydrogen or phenyl;
- R9 is either hydrogen or methyl;
- and
- R10 is either hydrogen, methyl, or phenyl;
- or a pharmaceutically acceptable salt or complex thereof.
6 more elements
A method of decreasing parathyroid hormone level in a patent to achieve a beneficial effect comprising the step of administering to said patient an effective amount of a compound selected from the group consisting of:
- 21S ((R)-N-(3-(2-chlorophenyl)propyl)-1-(3-propoxyphenyl)ethylamine);
- 21T ((R)-N-(3-(2-chlorophenyl)propyl)-1-(3-isopropoxyphenyl)ethylamine);
- 21U ((R)-N-(3-(2-chlorophenyl)propyl)-1(3-isobutoxyphenyl)ethylamine);
- 21Y ((R,R)-N-(4-(3-(trifluoromethyl)phenyl)-2-butyl)-1-(3-methoxyphenyl)ethylamine);
- 22J ((R)-N-(3-(3-(trifluoromethyl)phenyl)propyl)-1-(1-naphthyl)ethylamine);
- 23A ((R)-N-(4-(3-(trifluoromethoxy)phenyl)-2-butyl)-1-(3-methoxyphenyl)ethylamine);
- 23E ((R)-N-((3-(trifluoromethoxy)phenyl)methyl)-1-(1-naphthyl)ethylamine;
- 24B (N-((3-methyl-4-methoxyphenyl)methyl)-1-(2-(trifluoromethyl)phenyl)ethylamine);
- 24J ((R)-N-(3-(3-(trifluoromethoxy)phenyl)propyl)-1-(1-naphthyl)ethylamine;
- 24M ((R)-N-(3-(3,5-difluorophenyl)propyl)-1-(3-methoxyphenyl)ethylamine;
- 24V (N-((3-methyl-4-methoxyphenyl)methyl)-1(3-(ethylacetoxy)phenyl)ethylamine);
- 24X ((R)-N-((3-bromo-4-methoxyphenyl)methyl)-1-(1-naphthyl)ethylamine);
- 24Y ((R)-N-((3-chloro-4-ethoxyphenyl)methyl)-1-(1-naphthyl)ethylamine;
- 25C ((S,R)-N-(4-(3-trifluoromethyl)phenyl)-2-butyl)-1-(1-naphthyl)ethylamine);
- and
- 25D ((R,R)-N-(4-(3-trifluoromethyl)phenyl)-2-butyl)-1-(1-naphthyl)ethylamine);
- 25E ((R)-N-(3-phenylprop-2-en-1-yl)-1-(3-methoxyphenyl)ethylamine or a pharmaceutically acceptable salt or complex thereof.
14 more elements
A method of treating a patient having a disease selected from the group consisting of hyperparathyroidism, Paget's disease, a hypercalcemic disorder, osteoporosis, hypertension, and renal osteodystrophy, comprising the step of administering to said patient an effective amount of the compound of any of claims 1, 2, 3, 4, 5, 6, 7, 10, 11, 12, 1314, 15, 16, 17, 18 or 19 or 20.
Dependencies are inferred from the claim text.