Pentaerythritol derivatives, their production and use and intermediates for their synthesis
AssigneeISIS PHARMA GmbH
InventorsUlrich Hess, Anne-Katrin Windeck, Holger Brosig
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Abstract
The invention describes novel compounds derived from pentaerythritol of general formula I, XIV, XVI, XIX and XXII, the substituents being as defined in the description, which can be used as pharmaceutical active substances, especially for the treatment of cardiovascular diseases.
Claims27
Compounds of general formula I:
- in which
- R1, R2, R3 are identical to or different from one another and are CH2—ONO2, CH2—OR4 or R5, at least one of the substituents R1 to R2 being R5,
- R4 is H or C1- to C6-alkanoyl,
- R5 is COR6,
- R6 is OH, OR7, NH2, NHR7, NR72, N+R73X, NR8, NR9R10, NR11R12 or NH—NH2,
- R7 is linear or branched C1- to C6-alkyl, linear or branched C1- to C6-alkenyl, aryl, aralkyl, heteroaryl or heteroaralkyl,
- R8 is C1- to C6-alkylidene,
- R9, R12 are different from one another and are R7
- R11, R12 are identical to or different from one another and are NR72, N+R73X or NR8, and
- X is a halogen or a suitable anion,
- and therapeutically acceptable salts thereof, with the exception of the following compounds:
- a) 3-nitryloxy-2,2-bis(nitryloxymethyl)propionic acid and
- b) methyl 3-nitryloxy-2,2-bis(nitryloxymethyl)propionate.
Ethyl 3-nitryloxy-2,2 bis(nitryloxymethyl)propionate,
- propyl 3-nitryloxy-2,2 bis(nitryloxymethyl)propionate,
- butyl 3-nitryloxy-2,2-bis(nitryloxymethyl)propionate,
- benzyl 3-nitryloxy-2,2-bis(nitryloxymethyl)propionate,
- 3-nitryloxy-2,2-bis(nitryloxymethyl)propionamide,
- 3-nitryloxy-2,2-bis(nitryloxymethyl)propionic acid N-benzylamide,
- 3-nitryloxy-2,2-bis(nitryloxymethyl)propionic acid hydrazide,
- dimethyl 2,2-bis(nitryloxymethyl)malonate, and
- dimethyl 2-methoxycarbonyl-2-nitryloxymethylmalonate.
Sodium 3-nitryloxy-2,2-bis(nitryloxymethyl)propinate and potassium 3-nitryloxy-2,2-bis(nitryloxymethyl)propionate.
Compounds of general formula I:
- in which
- R1, R2, R3 are identical to or different from one another and are CH2—ONO2
- CH2—OR4 or R5, at least one of the substituents R1 to R3 being R5,
- R4 is H or C1- to C6-alkanoyl,
- R5 is COR6,
- R6 is Cl or Br for at least one of the substituents or is OH, OR7, NH2, NHR7, NR72, N+R73X−, NR8, NR9R10, NR11R12 or NH—NH2,
- R7 is linear or branched C1- to C6-alkyl, linear or branched C1- to C6-alkenyl, aryl, aralkyl, heteroaryl or heteroaralkyl,
- R8 is C1- to C6-alkylidene,
- R9, R10 are different from one another and are R7,
- R11, R12 are identical to or different from one another and are NR72, N+R73X− or NR8, and
- X is a halogen or a suitable anion.
3-nitryloxy-2,2-bis(nitryloxymethyl)propionyl chloride,
- 2,2-bis(nitryloxymethyl)malonyl dichloride, and
- 2-chlorocarbonyl-2-nitryloxymethymalonyl dichloride.
Process for the preparation of 3-nitryloxy-2,2-bis(nitryloxymethyl)propionic acid, wherein 3-nitryloxy-2,2-bis(nitryloxymethyl)propanol is oxidized directly to 3-nitryloxy-2,2-bis(nitryloxymethyl)propionic acid.
Process for the preparation of methyl 3-nitryloxy-2,2-bis(nitryloxymethyl)propionate, wherein a 3-nitryloxy-2,2-bis(nitryloxymethyl)propionyl halide is esterified with methanol.
Process for the preparation of methyl 3-nitryloxy-2,2-bis(nitryloxymethyl)propionate, wherein
- a) 3-nitryloxy-2,2-bis(nitryloxymethyl)propionic acid is converted to a 3-nitryloxy-2,2-bis(nitryloxymethyl)propionyl halide, and
- b) this acid halide is then esterified with methanol.
Dependencies are inferred from the claim text.