Nova Patents
EP0407780A2

Ranolazine and related piperazines used in the treatment of tissues experiencing a physical or chemical insult.

Abstract

Piperazine derivatives, particularly ranolazine, are useful for treatment of tissues experiencing a physical or chemical insult, and specifically for treating cardioplegia, hypoxic and/or reperfusion injury to cardiac or skeletal muscle or brain tissue, and for use in transplants.

EP0407780A2, drawing sheet 1
Sheet 1 of 4

Term

Term ended

Projected expiry passed 21 June 2010, 16.3 years ago.

  1. Priority
  2. Filed
  3. Published
  4. Projected expiry
  5. Today

15 claims: 10 independent, 5 dependent

  1. 1
    The use of a compound of the formula:or a pharmaceutically acceptable esters or acid addition salts thereof, wherein: R¹, R², R³, R⁴ and R⁵ are each independently hydrogen, lower alkyl, lower alkoxy, cyano, trifluoromethyl, halo, lower alkylthio, lower alkyl sulfinyl, lower alkyl sulfonyl, N-optionally substituted alkylamido, except that when R¹ is methyl, R⁴ is not methyl;or R² and R³ together form -OCH₂O-;R⁶, R⁷, R⁸, R⁹, and R¹⁰ are each independently hydrogen, lower acyl, aminocarbonylmethyl, cyano, lower alkyl, lower alkoxy, trifluoromethyl, halo, lower alkylthio, lower alkyl sulfinyl, lower alkyl sulfonyl, di-lower alkyl amino;R⁶ and R⁷ together form -CH=CH-CH=CH-;or R⁷ and R⁸ together form -OCH₂O-;R¹¹ and R¹² are each independently hydrogen or lower alkyl;and W is oxygen or sulfur;in the manufacture of a medicament for treating tissues experiencing a physical or chemical insult.
  2. 2
    The use of Claim 1 wherein R¹ and R⁵ are methyl.
  3. 3
    The use of Claim 2 wherein R², R³, R⁴, R¹¹ and R¹² are hydrogen.
  4. 4
    The use of Claim 3 wherein W is oxygen.
  5. 5
    The use of Claim 4 wherein R⁶ is methoxy and R⁷, R⁸, R⁹ and R¹⁰ are hydrogen, i.e., ranolazine.
  6. 6
    The use of any one of Claims 1-5, wherein a medicament for protecting the myocardium against global ischaemic damage induced by cardioplegia is prepared.
  7. 7
    The use of any one of Claims 1-5 wherein a medica­ment for protecting skeletal muscle against damage resulting from trauma or subsequent to muscle or systemic diseases is prepared.
  8. 8
    The use of any one of claims 1-5 wherein a medica­ment for treating shock conditions, including cardiogenic shock, is prepared.
  9. 9
    The use of any one of Claims 1-5 wherein a medica­ment for protecting neuronal tissue against ischaemia resulting from cardiac function impairment of from non-­cardiac conditions, including protecting brain tissue against ischaemia-induced metabolic disorders, is prepared.
  10. 10
    The use of any one of Claims 1-5 wherein a medicament for preserving donor tissues used in transplants, preferably renal transplants, skin grafts, cardiac trans­plants, lung transplants, corneal transplants, or liver transplants, is prepared.
  11. 11
    The use of any one of Claims 1-5 wherein a medicament for protecting myocardial tissue against ischae­mic damage in subjects with myocardial infarction is prepa­red.
  12. 12
    The use of any one of Claims 1-11 wherein said compound is ranolazine, or a pharmaceutically acceptable salt thereof.
  13. 13
    The use of any one of Claims 1-12 which comprises the combined use of said compound together with a second pharmaceutically active agent, such as TPA or streptokinase.
  14. 14
    A pharmaceutical composition containing a therapeutically effective amount, up to 5 mg/ml for liquid and semi-solid formulations, of a compound of the formula:or a pharmaceutically acceptable esters or acid addition salts thereof, wherein: R¹, R², R³, R⁴ and R⁵ are each independently hydrogen, lower alkyl, lower alkoxy, cyano, trifluoromethyl, halo, lower alkylthio, lower alkyl sulfinyl, lower alkyl sulfonyl, N-optionally substituted alkylamido, except that when R¹ is methyl, R⁴ is not methyl;or R² and R³ together form -OCH₂O-;R⁶, R⁷, R⁸, R⁹ and R¹⁰ are each independently hydrogen, lower acyl, aminocarbonylmethyl, cyano, lower alkyl, lower alkoxy, trifluoromethyl, halo, lower alkylthio, lower alkyl sulfinyl, lower alkyl sulfonyl, di-lower alkyl amino;R⁶ and R⁷ together form -CH=CH-CH=CH-;or R⁷ and R⁸ together form -OCH₂O-;R¹¹ and R¹² are each independently hydrogen or lower alkyl;and W is oxygen or sulfur, admixed with at least one pharmaceutically acceptable excipient.
  15. 15
    The pharmaceutical composition of Claim 14 wherein said compound is ranolazine.
Independent claims15