Substituted 1,2,3-triazolo[1,5-a]quinazolines for enhancing cognition

A compound of the formula (I):

• 19
• wherein:
• R1 is hydrogen, halogen or CN or a group C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C1-4alkoxy, C2-4alkenyloxy or C2-4alkynyloxy, each of which groups is unsubstituted or substituted with one or two halogen atoms or with a pyridyl or phenyl ring each of which rings may be unsubstituted or independently substituted by one or two halogen atoms or mitro, cyano, amino, methyl or CF3 groups;
• R2 is hydrogen, halogen or CN or a group C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C1-4alkoxy, C2-4alkenyloxy or C2-4alkynyloxy each of which groups is unsubstituted or substituted with one or two halogen atoms;
• W is selected from:
• (i) a cyclic amine containing from 4 to 7 ring atoms,
• (a) one of which is nitrogen which is the point of attachment to the rest of the molecule,
• (b) another of which is optionally nitrogen, oxygen or sulphur
• (c) when the optional nitrogen atom is present then, optionally fused to this atom and an adjacent carbon atom of the cyclic amine, is an aromatic ring containing 5 or 6 atoms, 1-4 of which are nitrogen and the remainder carbon,
• (d) the cyclic amine is optionally substituted by an oxo group,
• (e) the cyclic amine, and any fused aromatic ring present, is optionally substituted by up to three substitutents, chosed from:
• C1-4alkyl;
• C2-4alkenyl;
• C2-4alkynyl;
• halogen;
• CF3;
• hydroxy;
• hydroxyC1-4alkyl;
• C1-4alkylcarbonyl;
• C1-4alkoxycarbonyl;
• C1-4alkoxy;
• NR10R11 or (CH2)rNR10R11 where R10 and R11 are independently chosen from hydrogen, C1-4alkyl, and C1-4alkylcarbonyl and r is an integer from 1 to 4;
• C1-4alkylcarbonyl;
• C1-4alkoxycarbonyl;
• minocarbonyl;
• and (CH2)xU where x is an integer from zero to four and U is an aromatic group chosen from phenyl, a six-membered aromatic ring containing one or two nitrogen atoms and a five-membered aromatic ring containing 1, 2, 3 or 4 nitrogen atoms, U being optionally substituted with up to three substituents chosen from halogen, hydroxy, amino, C1-4alkoxy, C1-4alkyl and C1-4hydroxyalkyl;
• (ii) a five-membered heteroaromatic ring containing 1, 2, 3 or 4 nitrogen heteroatoms chosen from oxygen, nitrogen and sulphur, at most one of the heteroatoms being oxygen or sulphur, or a six-membered heteroaromatic ring containing one or two nitrogen atoms;
• the heteroaromatic ring being optionally fused to a pyridine or phenyl ring;
• the heteroaromatic ring and any fused ring present being optionally substituted by up to two groups chosen from hydroxy, halogen, amino, C1-4alkyl and C1-4alkoxy;
• (iii) L-Y-X wherein
• L is O, (CH)2, (CH2)2, S or NRn where Rn is H, C1-6alkyl, C1-4alkoxyC1-4alkyl or C3-6cycloalkyl;
• Y is a bond or optionally branched C1-4alkylene or Y is a group (CH2)jO or (CH2)jNR12 or (CH2)jNR12C1-2alkylene, j is 2, 3 or 4 and R12 is hydrogen or C1-4alkyl and Y is optionally substituted by an oxo group;
• and
• X is a 5-membered heteroaromatic ring containing 1, 2, 3 or 4 heteroatoms independently chosen from oxygen, nitrogen and sulphur, at most one of the heteroatoms being oxygen or sulphur, or a 6-membered heteroaromatic ring containing 1, 2 or 3 nitrogen atoms, the 5- or 6-membered heteroaromatic ring being optionally fused to a benzene, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperidinyl, piperazinyl, morpholinyl or thiomorpholinyl ring and the heteroaromatic ring, including any fused portion, is optionally substituted by Rx and/or Ry and/or Rz, where Rx is halogen, C1-4alkoxyC1-4alkenyl, OH, R3, OR3, OCOR3, COR3, NR4R5, CONR4R5, tri(C1-6alkyl)silylC1-6alkoxyC1-4alkyl, CN or R9, Ry is halogen, R3, OR3, OCOR3, NR4R5, CONR4R5 or CN and Rz is R3, OR3 or OCOR3, where R3 is C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, hydroxyC1-6alkyl and R3 is optionally mono, di- or tri-fluorinate, R4 and R5 are each independently hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl or CF3 or, where possible, R4 and R5, together with a nitrogen atom to which they are commonly attached, form a 4-7 membered heteroaliphatic ring containing the said nitrogen atom and optionally one other heteroatom selected from O, N and S, which heteroaliphatic ring is optionally substituted by C1-4alkyl, and R9 is benzyl or an aromatic ring containing either 6 atoms, 1, 2 or 3 of which are optionally nitrogen, or 5 atoms, 1, 2 or 3 of which are independently chosen from oxygen, nitrogen and sulphur, at most one of the atoms being oxygen or sulphur, and R9 is optionally substituted by one, two or three substituents independently chosen from halogen atoms and C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C1-4alkoxy, C2-4alkenyloxy and C2-4alkynyloxy groups each of which groups is unsubstituted or substituted by one, two or three halogen atoms, and when X is a pyridine derivative, the pyridine ring is optionally in the form of the N-oxide and providing that when X is a tetrazole derivative it is substituted by a C1-4alkyl group;
• or
• X is phenyl optionally substituted by one, two or three groups independently selected from halogen, cyano, C1-6alkyl, C2-6alkenyl, C2-6alkynyl and C3-6cycloalkyl;
• or
• X is C1-4alkyl or C1-4alkylcarbonyl;
• or
• X is a heteroaliphatic ring containing five or six atoms with one or two atoms chosen from oxygen, nitrogen and sulphur, which ring is optionally substituted by an oxo group, the ring being optionally fused to a benzene ring, and the ring being optionally substituted by halogen, C14alkyl, C1-4alkoxy or C1-4alkoxycarbonyl;
• Z is a 5-membered heteroaromatic ring containing 1, 2 or 3 heteroatoms independently selected from oxygen, nitrogen and sulphur, at most one of the heteroatoms being oxygen or sulphur and providing that when one of the atoms is oxygen or sulphur then at least one nitrogen atom is present, or a 6-membered heteroaromatic ring containing 2 or 3 nitrogen atoms, Z being optionally substituted by Rv and/or Rw, where Rv is halogen, R6, NR7R8, NR7COR8, CN, furyl, thienyl, phenyl, benzyl, pyridyl or a 5-membered heteroaromatic ring containing at least one nitrogen atom and optionally 1, 2 or 3 other heteroatoms independently selected from oxygen, nitrogen and sulphur, at most one of the other heteroatoms being oxygen or sulphur and Rw is R6 or CN;
• R6 is C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, hydroxyC1-6alkyl, C1-6alkoxy, C2-6alkenyloxy, C2-6alkynyloxy, CH2F or CF3;
• and
• R7 and R8 are each independently hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl or CF3 or R7 and R8, together with the nitrogen atom to which they are attached, form a 4-7 membered heteroaliphatic ring containing the nitrogen atom as the sole heteroatom;
• or a pharmaceutically acceptable salt thereof.