Calcium receptor-active compounds
AssigneeNPS Pharmaceuticals, Inc.
InventorsTeruyuki Sakai, Atsuya Takami, Rika Nagao
Life of this patent
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Abstract
A novel calcium receptor active compound having the formula is provided: Ar1—[CR1R2]p—X—[CR3R4]q—[CR5R6]—NR7—[CR8R9]—Ar2 wherein: Ar1 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; R1, R2, R3, R4, R5, R6, R7, R8 and R9 are, for example, hydrogen or alkyl; Ar2 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.
Claims24
A compound having the formula:
- Ar5—[CHR16]t—W—(CH2)u—CHR17)—NH—CH(R18)—AR6
- wherein:
- Ar5 is phenyl, indole, carbazole, pyridine, dibenzofuran, or fluorene, optionally substituted with one or more groups independentlyselected from the group consisting of unsubstituted lower alkyl, halogen, unsubstituted lower alkoxy, lower alkyl substituted with one or more halogens, lower alkoxy substituted with one or more halogens, nitro, dimethylamino, and unsubstituted phenyl;
- Ar6 is 3-methoxy phenyl or alpha-naphthyl;
- t is 0 or 1;
- u is an integer of from 0 to 11, inclusive;
- W is selected from the group consisting of oxygen, sulfur, sulfinyl, sulfonyl, carbonyl, and amino;
- R16 and R17 are H or unsubstituted lower alkyl;
- R18 is unsubstituted lower alkyl;
- or a pharmaceutically acceptable salt or hydrate of said compound.
A pharmaceutical composition comprising a compound, or a pharmaceutically acceptable salt or hydrate thereof, having the formula:
- Ar5—[CHR16]—W—(CH2)u—CHR17)—NH—CH(R18)—Ar6
- wherein:
- Ar5 is phenyl, indole, carbazole, pyridine, dibenzofuran, or fluorene, optionally substituted with one or more groups independentlyselected from the group consisting of unsubstituted lower alkyl, halogen, unsubstituted lower alkoxy, lower alkyl substituted with one or more halogens, lower alkoxy substituted with one or more halogens, nitro, dimethylamino, and unsubstituted phenyl;
- Ar6 is 3-methoxy phenyl or alpha-naphthyl;
- t is 0 or 1;
- u is an integer of from 0 to 11, inclusive;
- W is selected from the group consisting of oxygen, sulfur, sulfinyl, sulfonyl, carbonyl, and amino;
- R16 and R17 are H or unsubstituted lower alkyl;
- R18 is unsubstituted lower alkyl;
- or a pharmaceutically acceptable salt or hydrate of said compound.
(New) A method of treating a patient comprising administering to said patient a therapeutically effective amount of one or more of compounds, or a pharmaceutically acceptable salt or hydrate thereof, having the formula:
- Ar5—[CHR16]t—W—(CH2)u—CHR17)—NH—CH(R18)—Ar6
- wherein:
- Ar5 is phenyl, indole, carbazole, pyridine, dibenzofuran, or fluorene, optionally substituted with one or more groups independentlyselected from the group consisting of unsubstituted lower alkyl, halogen, unsubstituted lower alkoxy, lower alkyl substituted with one or more halogens, lower alkoxy substituted with one or more halogens, nitro, dimethylamino, and unsubstituted phenyl;
- Ar6 is 3-methoxy phenyl or alpha-naphthyl;
- t is 0 or 1;
- u is an integer of from 0 to 11, inclusive;
- W is selected from the group consisting of oxygen, sulfur, sulfinyl, sulfonyl, carbonyl, and amino;
- R16 and R17 are H or unsubstituted lower alkyl;
- R18 is unsubstituted lower alkyl;
- or a pharmaceutically acceptable salt or hydrate of said compound.
(New) A method for modulating the PTH level in a patient comprising administering to said patient an effective amount of a compound, or a pharmaceutically acceptable salt or hydrate thereof, having the formula:
- Ar5—[CHR16]t—W—(CH2)u—CHR17)—NH—CH(R18)—Ar6
- wherein:
- Ar5 is phenyl, indole, carbazole, pyridine, dibenzofuran, or fluorene, optionally substituted with one or more groups independentlyselected from the group consisting of unsubstituted lower alkyl, halogen, unsubstituted lower alkoxy, lower alkyl substituted with one or more halogens, lower alkoxy substituted with one or more halogens, nitro, dimethylamino, and unsubstituted phenyl;
- Ar6 is 3-methoxy phenyl or alpha-naphthyl;
- t is 0 or 1;
- u is an integer of from 0 to 11, inclusive;
- W is selected from the group consisting of oxygen, sulfur, sulfinyl, sulfonyl, carbonyl, and amino;
- R16 and R17 are H or unsubstituted lower alkyl;
- R18 is unsubstituted lower alkyl;
- or a pharmaceutically acceptable salt or hydrate of said compound.
(New) A method for modulating one or more Ca2+ receptors activities in a cell comprising administration to said cell one or more compounds, or a pharmaceutically acceptable salt or hydrate thereof, having the formula:
- Ar5—[CHR16]t—W—(CH2)u—CHR17)—NH—CH(R18)—Ar6
- wherein:
- Ar5 is phenyl, indole, carbazole, pyridine, dibenzofuran, or fluorene, optionally substituted with one or more groups independentlyselected from the group consisting of unsubstituted lower alkyl, halogen, unsubstituted lower alkoxy, lower alkyl substituted with one or more halogens, lower alkoxy substituted with one or more halogens, nitro, dimethylamino, and unsubstituted phenyl;
- Ar6 is 3-methoxy phenyl or alpha-naphthyl;
- t is 0 or 1;
- u is an integer of from 0 to 11, inclusive;
- W is selected from the group consisting of oxygen, sulfur, sulfinyl, sulfonyl, carbonyl, and amino;
- R16 and R17 are H or unsubstituted lower alkyl;
- R18 is unsubstituted lower alkyl;
- or a pharmaceutically acceptable salt or hydrate of said compound.
(New) A pharmaceutical composition for treatment of primary and secondary hyperparathyroidism comprising a compound, or a pharmaceutically acceptable salt or hydrate thereof, having the formula:
- Ar5—[CHR16]t—W—(CH2)u—CHR17)—NH—CH(R18)—Ar6
- wherein:
- Ar5 is phenyl, indole, carbazole, pyridine, dibenzofuran, or fluorene, optionally substituted with one or more groups independentlyselected from the group consisting of unsubstituted lower alkyl, halogen, unsubstituted lower alkoxy, lower alkyl substituted with one or more halogens, lower alkoxy substituted with one or more halogens, nitro, dimethylamino, and unsubstituted phenyl;
- Ar6 is 3-methoxy phenyl or alpha-naphthyl;
- t is 0 or 1;
- u is an integer of from 0 to 11, inclusive;
- W is selected from the group consisting of oxygen, sulfur, sulfinyl, sulfonyl, carbonyl, and amino;
- R16 and R17 are H or unsubstituted lower alkyl;
- R18 is unsubstituted lower alkyl;
- or a pharmaceutically acceptable salt or hydrate of said compound.
(New) A pharmaceutical composition for treatment of renalosteodystrophy comprising a compound, or a pharmaceutically acceptable salt or hydrate thereof, having the formula:
- Ar5—[CHR16]t—W—(CH2)u—CHR17)—NH—CH(R18)—Ar6
- wherein:
- Ar5 is phenyl, indole, carbazole, pyridine, dibenzofuran, or fluorene, optionally substituted with one or more groups independentlyselected from the group consisting of unsubstituted lower alkyl, halogen, unsubstituted lower alkoxy, lower alkyl substituted with one or more halogens, lower alkoxy substituted with one or more halogens, nitro, dimethylamino, and unsubstituted phenyl;
- Ar6 is 3-methoxy phenyl or alpha-naphthyl;
- t is 0 or 1;
- u is an integer of from 0 to 11, inclusive;
- W is selected from the group consisting of oxygen, sulfur, sulfinyl, sulfonyl, carbonyl, and amino;
- R16 and R17 are H or unsubstituted lower alkyl;
- R18 is unsubstituted lower alkyl;
- or a pharmaceutically acceptable salt or hydrate of said compound.
(New) A pharmaceutical composition for treatment of hypercalcemia comprising a compound, or a pharmaceutically acceptable salt or hydrate thereof, having the formula:
- Ar5—[CHR16]t—W—(CH2)u—CHR17)—NH—CH(R18)—Ar6
- wherein:
- Ar5 is phenyl, indole, carbazole, pyridine, dibenzofuran, or fluorene, optionally substituted with one or more groups independentlyselected from the group consisting of unsubstituted lower alkyl, halogen, unsubstituted lower alkoxy, lower alkyl substituted with one or more halogens, lower alkoxy substituted with one or more halogens, nitro, dimethylamino, and unsubstituted phenyl;
- Ar6 is 3-methoxy phenyl or alpha-naphthyl;
- t is 0 or 1;
- u is an integer of from 0 to 11, inclusive;
- W is selected from the group consisting of oxygen, sulfur, sulfinyl, sulfonyl, carbonyl, and amino;
- R16 and R17 are H or unsubstituted lower alkyl;
- R18 is unsubstituted lower alkyl;
- or a pharmaceutically acceptable salt or hydrate of said compound.
(New) A pharmaceutical composition for treatment of hypercalcemia malignancy comprising a compound, or a pharmaceutically acceptable salt or hydrate thereof, having the formula:
- Ar5—[CHR16]t—W—(CH2)u—CHR17)—NH—CH(R18)—Ar6
- wherein:
- Ar5 is phenyl, indole, carbazole, pyridine, dibenzofuran, or fluorene, optionally substituted with one or more groups independentlyselected from the group consisting of unsubstituted lower alkyl, halogen, unsubstituted lower alkoxy, lower alkyl substituted with one or more halogens, lower alkoxy substituted with one or more halogens, nitro, dimethylamino, and unsubstituted phenyl;
- Ar6 is 3-methoxy phenyl or alpha-naphthyl;
- t is 0 or 1;
- u is an integer of from 0 to 11, inclusive;
- W is selected from the group consisting of oxygen, sulfur, sulfinyl, sulfonyl, carbonyl, and amino;
- R16and R17 are H or unsubstituted lower alkyl;
- R18 is unsubstituted lower alkyl;
- or a pharmaceutically acceptable salt or hydrate of said compound.
(New) A pharmaceutical composition for treatment of osteoporosis comprising a compound, or a pharmaceutically acceptable salt or hydrate thereof, having the formula:
- Ar5—[CHR16]t—W—(CH2)u—CHR17)—NH—CH(R18)—Ar
- wherein:
- Ar5 is phenyl, indole, carbazole, pyridine, dibenzofuran, or fluorene, optionally substituted with one or more groups independentlyselected from the group consisting of unsubstituted lower alkyl, halogen, unsubstituted lower alkoxy, lower alkyl substituted with one or more halogens, lower alkoxy substituted with one or more halogens, nitro, dimethylamino, and unsubstituted phenyl;
- Ar6 is 3-methoxy phenyl or alpha-naphthyl;
- t is 0 or 1;
- u is an integer of from 0 to 11, inclusive;
- W is selected from the group consisting of oxygen, sulfur, sulfinyl, sulfonyl, carbonyl, and amino;
- R16 and R17 are H or unsubstituted lower alkyl;
- R18 is unsubstituted lower alkyl;
- or a pharmaceutically acceptable salt or hydrate of said compound.
Dependencies are inferred from the claim text.