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US 6,673,795 B2Granted
Pyrimidine, pyrazine and triazane derivatives
AssigneeHoffmann-La Roche Inc.
InventorsAlfred Binggeli, Hans-Peter Maerki, Thierry Masquelin, Vincent Mutel, Maurice Wilhelm, Wolfgang Wostl
Life of this patent
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Abstract
The present invention is a pyrimidine, triazine or pyrazine derivative of the formula or a pharmaceutically acceptable salt thereof wherein R1, R2, R3, R4, X, Y and Z are as defined in the specification. The invention is a pharmaceutical composition containing an effective amount of the compound of formula 1, its preparation and to a method of treatment, control or prevention of acute and/or chronic neurological disorders by administering a therapeutically effective amount of a compound of formula 1.
Claims38
A compound of the formula
- or a pharmaceutically acceptable salt thereof, wherein
- R1 is selected from the group consisting of nitro and cyano;
- R2 is selected from the group consisting of hydrogen, (C1-C7)-alkyl and —NHR10;
- wherein
- R10 is selected from the group consisting of hydrogen, (C1-C7)-alkyl, —(CH2)m—OR11, —(CH2)p—(C3-C6)-cycloalkyl, —(CH2)m—NH—C(O)O—(C1-C7)-alkyl and —(CH2)p-pyridyl;
- wherein
- R11 is selected from the group consisting of hydrogen and (C1-C7)-alkyl;
- R3 is selected from the group consisting of hydrogen, (C1-C7)-alkyl, fluoro, hydroxy, (C1-C7)-alkoxy, (C1-C7)-alkylthio, cyano and nitro;
- R4 is selected from the group consisting of hydrogen and fluoro;
- is selected from the group consisting of
- R5 is selected from the group consisting of hydrogen, (C1-C7)-alkyl, (C1-C7)-alkenyl, —(CH2)m—OR11, fluoro-(C1-C7)-alkyl and —(CH2)n—CN;
- R6 is selected from the group consisting of (C1-C7)-alkyl, halogen, hydroxy, (C1-C7)-alkoxy, (C1-C7)-alkylthio, —O—(CH2)mOR11, —O-fluoro-(C1-C7)-alkyl and —NHR12;
- and
- R12 is selected from the group consisting of (C1-C7)-alkyl, —(CH2)m—OR11, —(CH2)p—(C3-C6)-cycloalkyl and —(CH2)p-pyridyl;
- R7 is selected from the group consisting of hydrogen, (C1-C7)-alkyl and phenyl;
- R8 is selected from the group consisting of hydrogen, (C1-C7)-alkyl and phenyl;
- Z is selected from the group consisting of
- R9 is selected from the group consisting of hydrogen, hydroxy and cyano;
- m is independently from each other in each occurrence 2, 3, 4, 5 or 6;
- n is independently from each other in each occurrence 1, 2, 3, 4, 5 or 6;
- and
- p is independently from each other in each occurrence 0, 1, 2, 3, 4, 5 or 6.
19 more elements
A process for the manufacture of a compound of formula comprising reacting a compound of formula
- wherein R13 is halogen, with a compound of formula
- forming a compound of formula
- wherein
- R1 is selected from the group consisting of nitro and cyano;
- R2 is selected from the group consisting of hydrogen, (C1-C7)-alkyl and —NHR10;
- wherein
- R10 is selected from the group consisting of hydrogen, (C1-C7)-alkyl, —(CH2)m—OR11, —(CH2)p—(C3-C6)-cycloalkyl, —(CH2)m—NH—C(O)O—(C1-C7)-alkyl and —(CH2)p-pyridyl;
- wherein
- R11 is selected from the group consisting of hydrogen and (C1-C7)-alkyl;
- R3 is selected from the group consisting of hydrogen, (C1-C7)-alkyl, fluoro, hydroxy, (C1-C7)-alkoxy, (C1-C7)-alkylthio, cyano and nitro;
- R4 is selected from the group consisting of hydrogen and fluoro;
- is selected from the group consisting of
- R5 is selected from the group consisting of hydrogen, (C1-C7)-alkyl, (C1-C7)-alkenyl, —(CH2)m—OR11, fluoro-(C1-C7)-alkyl and —(CH2)n—CN;
- and
- Z is selected from the group consisting of
- R9 is selected from the group consisting of hydrogen, hydroxy and cyano.
13 more elements
A process for the manufacture of a compound of formula I or a pharmaceutically acceptable salts thereof, comprising reacting a compound of formula
- wherein R13 is halogen, with a compound of formula
- to obtain a compound of formula
- wherein
- R1 is selected from the group consisting of nitro and cyano;
- R2 is selected from the group consisting of hydrogen, (C1-C7)-alkyl and —NHR10;
- wherein
- R10 is selected from the group consisting of hydrogen, (C1-C7)-alkyl, —(CH2)m—OR11, —(CH2)p—(C3-C6)-cycloalkyl, —(CH2)m—NH—C(O)O—(C1-C7)-alkyl
- and —(CH2)p-pyridyl;
- wherein
- R11 is selected from the group consisting of hydrogen and (C1-C7)-alkyl;
- R3 is selected from the group consisting of hydrogen, (C1-C7)-alkyl, fluoro, hydroxy, (C1-C7)-alkoxy, (C1-C7)-alkylthio, cyano and nitro;
- R4 is selected from the group consisting of hydrogen and fluoro;
- is selected from the group consisting of
- R7 is selected from the group consisting of hydrogen, (C1-C7)-alkyl and phenyl;
- and
- Z is selected from the group consisting of
- R9 is selected from the group consisting of hydrogen, hydroxy and cyano.
14 more elements
A process for the manufacture of a compound of formula I or a pharmaceutically acceptable salts thereof, comprising reacting a compound of formula
- wherein R13 is halogen, with a compound of formula
- to obtain a compound of formula
- wherein
- R1 is selected from the group consisting of nitro and cyano;
- R2 is selected from the group consisting of hydrogen, (C1-C7)-alkyl and —NHR10;
- wherein
- R10 is selected from the group consisting of hydrogen, (C1-C7)-alkyl, —(CH2)m—OR11, —(CH2)p—(C3-C6)-cycloalkyl, —(CH2)m—NH—C(O)O—(C1-C7)-alkyl
- and —(CH2)p-pyridyl;
- wherein
- R11 is selected from the group consisting of hydrogen and (C1-C7)-alkyl;
- R3 is selected from the group consisting of hydrogen, (C1-C7)-alkyl, fluoro, hydroxy, (C1-C7)-alkoxy, (C1-C7)-alkylthio, cyano and nitro;
- R4 is selected from the group consisting of hydrogen and fluoro;
- is selected from the group consisting of
- R8 is selected from the group consisting of hydrogen, (C1-C7)-alkyl and phenyl;
- and
- Z is selected from the group consisting of
- R9 is selected from the group consisting of hydrogen, hydroxy and cyano.
14 more elements
A process for the manufacture of a compound of formula I or a pharmaceutically acceptable salts thereof, comprising reacting a compound of formula
- wherein R13 is halogen, with a compound of formula
- and substituting the thiomethyl group with the respective nucleophiles to obtain a compound of formula
- wherein R21 is —NHR10 and
- R1 is selected from the group consisting of nitro and cyano;
- R3 is selected from the group consisting of hydrogen, (C1-C7)-alkyl, fluoro, hydroxy, (C1-C7)-alkoxy, (C1-C7)-alkylthio, cyano and nitro;
- R4 is selected from the group consisting of hydrogen and fluoro;
- is selected from the group consisting of
- Z is selected from the group consisting of
- R9 is selected from the group consisting of hydrogen, hydroxy and cyano.
6 more elements
Dependencies are inferred from the claim text.