Claims for Patent: 8,193,176

Summary for Patent: 8,193,176

Title:	Phenylpyrazole derivatives
Abstract:	The present invention provides a prophylactic or therapeutic agent for dementia, Alzheimer\'s disease, attention-deficit hyperactivity disorder, schizophrenia, eating disorders, obesity, diabetes, hyperlipidemia, sleep disorders, narcolepsy, sleep apnea syndrome, circadian rhythm disorder, depression, allergic rhinitis or other diseases. A phenylpyrazole derivative represented by formula (1) or a pharmaceutically acceptable salt thereof: ##STR00001## {wherein R.sup.1 and R.sup.2, which may be the same or different, each represent C.sub.1-C.sub.6 alkyl or C.sub.3-C.sub.8 cycloalkyl, or R.sup.1 and R.sup.2 are attached to each other together with their adjacent nitrogen atom to form a 4- to 7-membered saturated heterocyclic ring (wherein said saturated heterocyclic ring may be substituted with halogen or C.sub.1-C.sub.6 alkyl), n represents an integer of 0 to 2, T represents a hydrogen atom, halogen or C.sub.1-C.sub.6 alkyl, and R represents formula (I): ##STR00002## or the like}.
Inventor(s):	Nakamura; Toshio (Toshima-ku, JP), Tatsuzuki; Makoto (Toshima-ku, JP), Nozawa; Dai (Toshima-ku, JP), Tamita; Tomoko (Toshima-ku, JP), Masuda; Seiji (Toshima-ku, JP), Ohta; Hiroshi (Toshima-ku, JP), Kashiwa; Shuhei (Toshima-ku, JP), Fujino; Aya (Toshima-ku, JP), Chaki; Shigeyuki (Toshima-ku, JP), Shimazaki; Toshiharu (Toshima-ku, JP)
Assignee:	Taisho Pharmaceutical Co., Ltd (Tokyo, JP)
Application Number:	12/951,978
Patent Claims:	1. A method for treating diseases that involve histamine H3 receptor selected from the group consisting of dementia, Alzheimer's disease, attention-deficit hyperactivity disorder, schizophrenia, epilepsy, central convulsion, obesity, diabetes, hyperlipidemia, narcolepsy, sleep apnea syndrome, circadian rhythm disorder, depression and allergic rhinitis, which comprises administering to a patient in need thereof an effective amount of a phenylpyrazole derivative represented by the following formula or a pharmaceutically acceptable salt thereof: ##STR00124## wherein R.sup.1 and R.sup.2 are attached to each other together with their adjacent nitrogen atom to form a 5- to 6-membered saturated heterocyclic ring (wherein said saturated heterocyclic ring may be substituted with C.sub.1-C.sub.6 alkyl), T represents a hydrogen atom or halogen, Z.sup.1 represents --CH.sub.2--, --O-- or --NR.sup.11-- (wherein R.sup.11 represents hydrogen or C.sub.1-C.sub.6 alkyl), p represents an integer of 0 to 3, r represents an integer of 0 to 2, R.sup.3 represents halogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, hydroxy or oxo (provided that when Z.sup.1 is --CH.sub.2--, the hydrogen atom(s) may be replaced by R.sup.3). 2. The method according to claim 1, wherein the phenylpyrazole derivative is represented by the following formula: ##STR00125## wherein Z.sup.1 represents --CH.sub.2-- or --O--, p represents an integer of 0 to 3, r represents an integer of 0 to 2, T represents a hydrogen atom or halogen, R.sup.3 represents halogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, hydroxy or oxo (provided that when Z.sup.1 is --CH.sub.2--, the hydrogen atom(s) may be replaced by R.sup.3), and R.sup.A represents C.sub.1-C.sub.6 alkyl. 3. The method according to claim 1, wherein Z.sup.1 represents --O--, and T represents a hydrogen atom. 4. The method according to claim 1, wherein p represents 2. 5. The method according to claim 2, wherein R.sup.A represents methyl. 6. The method according to claim 1, wherein the phenylpyrazole derivative is selected from the group consisting of: 4-{[1-(4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}phenyl)-1H-pyrazol-4-yl- ]carbonyl}morpholine, 4-{[1-(4-{3-[(2S)-2-methylpyrrolidin-1-yl]propoxy}phenyl)-1H-pyrazol-4-yl- ]carbonyl}morpholine, 4-({1-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]-1H-pyrazol-4-yl}carbonyl)morph- oline, 4-({1-[4-(3-piperidin-1-ylpropoxy)phenyl]-1H-pyrazol-4-yl}carbonyl)- morpholine, 4-[(1-{4-[3-(2,2-dimethylpyrrolidin-1-yl)propoxy]phenyl}-1H-pyrazol-4-yl)- carbonyl]morpholine, azetidin-1-yl-(1-{4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl}-1H-pyrazo- l-4-yl)methanone, 4-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-1-(4-{3-[(2R)-2-methylpyrrolidi- n-1-yl]propoxy}phenyl)-1H-pyrazole, [(2R,6S)-2,6-dimethylmorpholin-4-yl][1-(4-{3-[(2R)-2-methylpyrrolidin-1-y- l]propoxy}phenyl)-1H-pyrazol-4-yl]methanone, [1-(4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}phenyl)-1H-pyrazol-4-yl](1- ,4-oxazepan-4-yl)methanone, (4-methylpiperazin-1-yl)[1-(4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}ph- enyl)-1H-pyrazol-4-yl]methanone, [1-(4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}phenyl)-1H-pyrazol-4-yl](p- yrrolidin-1-yl)methanone, (1-{4-[3-(3-methylpyrrolidin-1-yl)propoxy]phenyl}-1H-pyrazol-4-yl)(morpho- lin-4-yl)methanone, (1-{4-[3-(2-ethylpyrrolidin-1-yl)propoxy]phenyl}-1H-pyrazol-4-yl)(morphol- in-4-yl)methanone, [1-(3-fluoro-4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxyl}phenyl)-1H-pyraz- ol-4-yl](morpholin-4-yl)methanone, [1-(3-bromo-4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxyl}phenyl)-1H-pyrazo- l-4-yl](morpholin-4-yl)methanone, and (2-hydroxymorpholin-4-yl)[1-(4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}p- henyl)-1H-pyrazol-4-yl]methanone. 7. The method according to claim 1, wherein the phenylpyrazole derivative is 4-{[1-(4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}phenyl)-1H-pyrazol-4- -yl]carbonyl}morpholine, represented by the following formula: ##STR00126##

Details for Patent 8,193,176

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Jubilant Hollisterstier Llc	N/A	positive skin test control-histamine	Injection	103891	03/13/1924		2027-11-13