Claims for Patent: 7,304,174

Summary for Patent: 7,304,174

Title:	CaSR antagonist
Abstract:	A compound represented by the following formula (1), a pharmaceutically acceptable salt thereof or an optically active form thereof: ##STR00001## wherein each symbol is as defined in the specification. A compound having a calcium-sensing receptor antagonistic action, a pharmaceutical composition comprising the compound, particularly a calcium receptor antagonist and a therapeutic drug for osteoporosis are provided.
Inventor(s):	Shinagawa; Yuko (Takatsuki, JP), Inoue; Teruhiko (Takatsuki, JP), Kiguchi; Toshihiro (Takatsuki, JP), Ikenogami; Taku (Takatsuki, JP), Ogawa; Naoki (Takatsuki, JP), Fukuda; Kenji (Takatsuki, JP), Nakagawa; Takashi (Takatsuki, JP), Shindo; Masanori (Takatsuki, JP), Soejima; Yuki (Takatsuki, JP)
Assignee:	Japan Tobacco Inc. (Tokyo, JP)
Application Number:	10/830,480
Patent Claims:	1. A compound represented by the following formula (1''): ##STR00224## wherein R.sup.1' is a hydroxyl group or a C.sub.1-6 alkoxy group, R.sup.2' is a hydroxyl group, a halogen atom, an amino group, a C.sub.1-7 acylamino group, a halo C.sub.1-6 alkyl group, a C.sub.1-6 alkoxy-carbonyl group, a C.sub.1-6 alkoxy group, a halo C.sub.1-6 alkoxy group, a C.sub.1-6 alkyl group, a hydroxy-C.sub.1-6 alkyl group, a di(C.sub.1-6 alkyl)amino group or a nitro group, R.sup.4' is a C.sub.1-6 alkyl group or a C.sub.3-6 cycloalkyl group, R.sup.6' is a halogen atom, a C.sub.1-6 alkyl group, a C.sub.1-6 alkoxy group or a halo C.sub.1-6 alkyl group, or when R.sup.7' is adjacent, R.sup.6' and R.sup.7' are linked to form --CH.dbd.CH--CH.dbd.CH--, and R.sup.7' is a hydrogen atom, a halogen atom, a C.sub.1-6 alkyl group, a C.sub.1-6 alkoxy group or a halo C.sub.1-6 alkyl group, an optically active form thereof, a pharmaceutically acceptable salt thereof, or an optically active form of the salt thereof. 2. A compound represented by the following formula (1'.sup.''): ##STR00225## wherein R.sup.2'' is a C.sub.1-6 alkyl group, R.sup.4'' is a methyl group or a cyclopropyl group, R.sup.6'' is a halogen atom or a C.sub.1-6 alkyl group, and R.sup.7'' is a hydrogen atom, a halogen atom, a C.sub.1-6 alkyl group, a C.sub.1-6 alkoxy group or a halo C.sub.1-6 alkyl group, an optically active form thereof, a pharmaceutically acceptable salt thereof, or an optically active form of the salt thereof. 3. The compound of claim 1 or 2, which is selected from the group consisting of 2'-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-- hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 2'-[1-[(2R)-3-[[1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-yl]amino]-2-- hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 2'-[1-[(2R)-3-[[1-(3-chloro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-- hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 2'-[1-[(2R)-3-[[1-(4-chloro-3-methylphenyl)-2-methylpropan-2-yl]amino]-2-- hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 2'-[1-[(2R)-3-[[1-(4-chloro-2-fluorophenyl)-2-methylpropan-2-yl]amino]-2-- hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 2'-[1-[(2R)-3-[[1-(2-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-- hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 2'-[1-[(2R)-3-[[1-(4-ethyl-3-fluorophenyl)-2-methylpropan-2-yl]amino]-2-h- ydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 2'-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-- hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 2'-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-- hydroxypropoxy]ethyl]-3-methylbiphenyl-5-carboxylic acid, 2'-[(cyclopropyl)[(2R)-3-[[1-(4-chloro-2-fluorophenyl)-2-methylpropan-2-y- l]amino]-2-hydroxypropoxy]methyl]-3-methylbiphenyl-4-carboxylic acid, 2'-[(cyclopropyl)[(2R)-3-[[1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-y- l]amino]-2-hydroxypropoxy]methyl]-3-methylbiphenyl-4-carboxylic acid, 3-methyl-2'-[1-[(2R)-3-[[1-(3,4-dimethylphenyl)-2-methylpropan-2-yl]amino- ]-2-hydroxypropoxy]ethyl]biphenyl-4-carboxylic acid, 2'-[1-[(2R)-3-[[1-(4-methylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypr- opoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 2'-[1-[(2R)-3-[[1-(4-chloro-3-methoxyphenyl)-2-methylpropan-2-yl]amino]-2- -hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 2'-[1-[(2R)-3-[[1-(4-ethylphenyl)-2-methylpropan-2-yl]amino]-2-hydroxypro- poxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 3-ethyl-2'-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]a- mino]-2-hydroxypropoxy]ethyl]biphenyl-4-carboxylic acid, 2'-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-- hydroxypropoxy]ethyl]-3-isopropylbiphenyl-4-carboxylic acid, 2'-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-- hydroxypropoxy]ethyl]-3-propylbiphenyl-4-carboxylic acid, 2'-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-- hydroxypropoxy]ethyl]-3-isobutylbiphenyl-4-carboxylic acid, 3-ethyl-2'-[1-[(2R)-3-[[1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-yl]a- mino]-2-hydroxypropoxy]ethyl]biphenyl-4-carboxylic acid, 2'-[1-[(2R)-3-[[1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-yl]amino]-2-- hydroxypropoxy]ethyl]-3-isopropylbiphenyl-4-carboxylic acid, 2'-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-- hydroxypropoxy]ethyl]-3-(1-methylpropyl)biphenyl-4-carboxylic acid, 2'-[1-[(2R)-3-[[1-(3-chlorophenyl)-2-methylpropan-2-yl]amino]-2-hydroxypr- opoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 2'-[1-[(2R)-3-[[1-(3,4-dichlorophenyl)-2-methylpropan-2-yl]amino]-2-hydro- xypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 2'-[1-[(2R)-3-[[1-(3-methoxy-4-methylphenyl)-2-methylpropan-2-yl]amino]-2- -hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 2'-[1-[(2R)-3-[[1-(3,5-dichlorophenyl)-2-methylpropan-2-yl]amino]-2-hydro- xypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 2'-[1-[(2R)-3-[[1-(4-chloro-3-trifluoromethylphenyl)-2-methylpropan-2-yl]- amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, 2'-[1-[(2R)-3-[[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]-2-- hydroxypropoxy]ethyl]-3-t-butylbiphenyl-4-carboxylic acid, 2'-[1-[(2R)-3-[[1-(4-chloro-2-fluorophenyl)-2-methylpropan-2-yl]amino]-2-- hydroxypropoxy]ethyl]-3-t-butylbiphenyl-4-carboxylic acid, 2'-[1-[(2R)-3-[[1-(4-chloro-3-fluorophenyl)-2-methylpropan-2-yl]amino]-2-- hydroxypropoxy]ethyl]-3-t-butylbiphenyl-4-carboxylic acid and 2'-[1-[(2R)-3-[[1-(3-trifluoromethyl-4-methylphenyl)-2-methylpropan-2-yl]- amino]-2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid an optically active form thereof, a pharmaceutically acceptable salt thereof or an optically active form of the salt thereof. 4. 2'-[1-[(2R)-3-[[1-(3-Fluoro-4-methylphenyl)-2-methylpropan-2-yl]amino]- -2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, an optically active form thereof, a pharmaceutically acceptable salt thereof or an optically active form of the salt thereof. 5. 2'-[1-[(2R)-3-[[1-(4-Chloro-3-fluorophenyl)-2-methylpropan-2-yl]amino]- -2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, an optically active form thereof, a pharmaceutically acceptable salt thereof or an optically active form of the salt thereof. 6. 2'-[1-[(2R)-3-[[1-(3-Chloro-4-methylphenyl)-2-methylpropan-2-yl]amino]- -2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, an optically active form thereof, a pharmaceutically acceptable salt thereof or an optically active form of the salt thereof. 7. 2'-[1-[(2R)-3-[[1-(4-Chloro-2-fluorophenyl)-2-methylpropan-2-yl]amino]- -2-hydroxypropoxy]ethyl]-3-methylbiphenyl-4-carboxylic acid, an optically active form thereof, a pharmaceutically acceptable salt thereof or an optically active form of the salt thereof. 8. A pharmaceutical composition comprising a pharmaceutically acceptable carrier, and a compound of any of claims 1-2 or 4-7, an optically active form thereof, a pharmaceutically acceptable salt thereof or an optically active form of the salt thereof as an active ingredient. 9. A method for treating osteoporosis, which comprises administering an effective amount of a composition comprising a pharmaceutically acceptable carrier, and a compound of any one of claims 1-2 and 4-7, an optically active form thereof, a pharmaceutically acceptable salt thereof or an optically active form of the salt thereof, as an active ingredient. 10. The method of claim 9, further comprising concomitant administration of said composition with a different therapeutic drug for osteoporosis. 11. The method of claim 10, wherein the different therapeutic drug for osteoporosis is selected from the group consisting of a calcium agent, a vitamin D preparation, a vitamin K preparation, a female hormone preparation, an estrogen antagonist preparation, an anabolic steroid preparation, a parathyroid hormone preparation, a calcitonin preparation, a bisphosphonate preparation and an ipriflavone preparation. 12. A calcium receptor antagonist comprising a pharmaceutically acceptable carrier, and a compound of any one of claims 1-2 and 4-7, an optically active form thereof, a pharmaceutically acceptable salt thereof or an optically active form of the salt thereof as an active ingredient. 13. A PTH secretagogue comprising a pharmaceutical acceptable carrier and a compound of any one of claims 1-2 and 4-7, an optically active form thereof, a pharmaceutically acceptable salt thereof or an optically active form of the salt thereof as an active ingredient.

Details for Patent 7,304,174

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2023-04-23