Piperazine compounds and antithrombotic pharmaceutical composition comprising the same

• US 4,797,399 A
• Filed: 12/23/1986
• Issued: 01/10/1989
• Est. Priority Date: 01/17/1986
• Status: Expired due to Fees

• Current Assignee: Fujisawa Pharmaceutical Company Limited No 3 4-Chome Doshomachi Higashi-Ku Osaka-Shi Japan
• Original Assignee: Fujisawa Pharmaceutical Co., Ltd. (Astellas Pharma Incorporated)
• Inventors: Ueda, Ikuo, Okumura, Hiroyuki, Tsuji, Kiyoshi, Matsuo, Masaaki, Nakaguchi, Osamu
• Primary Examiner(s): Daus, Donald G.
• Assistant Examiner(s): TSANG, CECILIA J
• Application Number:
  US06/945,853
• Time in Patent Office: 749 Days
• Field of Search: 544/362, 544/368, 544/373, 514/253
• US Class Current: 514/253.04
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: C07D 209/38 in positions 2 and 3, e.g. isatin
• CPC Class Codes: C07D 209/40 Nitrogen atoms, not forming part of a nitro radical, e.g. isatin semicarbazone
• CPC Class Codes: C07D 263/58 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
• CPC Class Codes: C07D 277/68 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
• CPC Class Codes: C07D 277/82 Nitrogen atoms
• CPC Class Codes: C07D 417/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 513/04 Ortho-condensed systems

Abstract

The present invention relates to N-containing fused heterocyclic compounds of the formula: ##STR1## wherein R₁ and R₂ are each hydrogen, halogen, aryl, lower alkyl, halo (lower) alkyl or nitro,

R₃ is lower alkylene,

R₄ and R₅ are each lower alkylene,

X is CH or N,

Y is S, O, NH, C═N--OH or CO,

Z is O or NH, and

A is hydrogen, nitroso, amidino, a group of ##STR2## wherein R₆ and R₇ are each hydrogen, lower alkyl, acyl, or lower alkaneimidoyl which may be substituted with esterified carboxy, or a group of the formula:

--N═R.sub.8,

wherein R₈ is lower alkylidene which may be substituted with aryl optionally substituted with suitable substituent(s).

The compounds are useful for treatment of thrombosis, inflammation, or allergic disease.

Claims

1. A compound of the formula:

##STR6## wherein R² is halogen,

R³ is lower alkylene,

R⁹ is hydrogen or lower alkyl,

X is CH or N, and

A is hydrogen, a group of the formula;

##STR7## wherein R⁶ and R⁷ are each hydrogen, lower alkanoyl or lower alkaneimidoyl, or a group of the formula;

--N═

R⁸ wherein R⁸ is lower alkylidene,

or a pharmaceutical acceptable salt thereof.

2. A compound of claim 1, wherein

R² is chlorine,

R³ is methylene, and

R⁹ is hydrogen or methyl,

A is hydrogen, a group of the formula:

##STR8## wherein R⁶ and R⁷ are each hydrogen, formyl or acetimidoyl, or a group of the formula;

--N═

R⁸ wherein R⁸ is methylene.

3. A compound of claim 2, wherein

R⁹ is hydrogen, X is CH and

A is amino.

4. A compound of claim 3, which is

5-chloro-3-[(4-amino-1-piperazinyl)carbonylmethyl]-2-benzothiazolinone or its hydrochloride.

5. An antithrombotic pharmaceutical composition comprising, as an active ingredient, an effective amount of a compound of claim 1 or pharmaceutically acceptable salt thereof in association with pharmaceutically acceptable carrier or excipient.

6. A method for the treatment of thrombosis in a human being or animal comprising administering an effective amount of a compound of claim 1 or pharmaceutically acceptable salt thereof.