Arylpiperidinol and arylpiperidine derivatives and pharmaceuticals containing the same

• US 7,498,344 B2
• Filed: 03/15/2004
• Issued: 03/03/2009
• Est. Priority Date: 07/22/1996
• Status: Expired due to Fees

• Current Assignee: Asubio Pharma Co., Ltd. (Daiichi Sankyo Company Limited)
• Original Assignee: Asubio Pharma Co., Ltd. (Daiichi Sankyo Company Limited)
• Inventors: Tamura, Shigeki, Annoura, Hirokazu, Nakanishi, Kyoko
• Primary Examiner(s): Desai; Rita J
• Application Number:
  US10/799,681
• Publication Number:
  US 20040186138A1
• Time in Patent Office: 1,814 Days
• Field of Search: 546/217, 519/330
• US Class Current: 514/317
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 211/12 with only hydrogen atoms attached to the ring nitrogen atom
• CPC Class Codes: C07D 211/14 with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
• CPC Class Codes: C07D 211/18 with substituted hydrocarbon radicals attached to ring carbon atoms
• CPC Class Codes: C07D 211/44 attached in position 4
• CPC Class Codes: C07D 211/52 having an aryl radical as the second substituent in position 4
• CPC Class Codes: C07D 211/70 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms

Abstract

A pharmaceutical composition, especially a pharmaceutical composition for the alleviation or treatment of symptoms due to ischemic diseases and symptoms derived from seizures, epilepsy, and migraine, and a Ca²⁺ overload suppressant, containing an arylpiperidinol or arylpiperidine derivative having the formula (I):

wherein, R is H, an optionally substituted phenyl, an optionally substituted phenoxy, or an optionally substituted benzoyl, A is a connecting bond, a cycloalkylene, or an alkenylene optionally substituted with a lower alkyl, B is an alkylene optionally substituted with OH or an alkoxy or —NHCO(CH₂)_n— where n is an integer of 1 to 5, E is a connecting bond, O, or a methylene, X is OH or H provided that when E is O or a methylene, X is not H, and Y and Z are independently H, a halogen, an alkoxy, or an alkyl optionally substituted with a halogen.

Claims

1. A compound having the formula (I′

);

2. A compound or its pharmaceutically acceptable salt as claimed in claim 1, wherein, in the formula (I′

), R′

, A, B, and X are selected from the group consisting of;

1) R′

is a phenyl group optionally substituted with a substituent selected from the group consisting of a halogen atom, a hydroxyl group, a C1-C5 optionally branched alkoxy group, and a C1-C5 optionally branched alkyl group optionally substituted with a halogen atom, A is a connecting bond, B is an alkylene group substituted with a hydroxyl group, and X is a hydroxyl group;

2) R′

is a phenoxy group optionally substituted with a substituent selected from the group consisting of a halogen atom, a hydroxyl group, a C1-C5 optionally branched alkoxy group, and a C1-C5 optionally branched alkyl group optionally substituted with a halogen atom, A is a connecting bond, B is an alkylene group substituted with a hydroxyl group, and X is a hydroxyl group; and

3) R′

is a benzoyl group optionally substituted with a substituent selected from the group consisting of a halogen atom, a hydroxyl group, a C1-C5 optionally branched alkoxy group, a C1-C5 optionally branched alkyl group optionally substituted with a halogen atom, A is a connecting bond, B is an alkylene group optionally substituted with a hydroxyl group or an alkoxy group and X is a hydroxyl group where further E is an oxygen atom, Y and Z may be the same or different from each other and represent a hydrogen atom, a halogen atom, an alkoxy group, or an alkyl group optionally substituted with a halogen atom.

3. A compound or its pharmaceutically acceptable salt as claimed in claim 1 or claim 2, wherein, in the formula (I′

), R′

is a benzoyl group optionally substituted with a substituent selected from the group consisting of a halogen atom, a hydroxyl group, a C1-C5 optionally branched alkoxy group, a C1-C5 optionally branched alkyl group optionally substituted with a halogen atom, A is a connecting bond, and X is a hydroxyl group.

4. A compound or its pharmaceutically acceptable salt as claimed in claim 1 or claim 2, wherein, in the formula (I′

), R′

is a phenyl group optionally substituted with a substituent selected from the group consisting of a halogen atom, a hydroxyl group, a C1-C5 optionally branched alkoxy group, and a C1-C5 optionally branched alkyl group optionally substituted with a halogen atom, A is a connecting bond, B is a dimethylene group substituted with a hydroxyl group, and X is a hydroxyl group.

5. A compound or its pharmaceutically acceptable salt as claimed in claim 1 or claim 2, wherein, in the formula (I′

), R′

is a phenoxy group optionally substituted with a substituent selected from the group consisting of a halogen atom, a hydroxyl group, a C1-C5 optionally branched alkoxy group, and a C1-C5 optionally branched alkyl group optionally substituted with a halogen atom, A is a connecting bond, B is a trimethylene group substituted with a hydroxyl group, and X is a hydroxyl group.

6. A pharmaceutical composition containing the compound having the formula (I′

) according to claim 1 or its pharmaceutically acceptable salt and a pharmaceutical acceptable carrier.