Compounds for treating fundic disaccomodation

A method of treating warm-blooded animals suffering from disturbed, hampered or impaired accommodation of the fundus to food ingestion comprising administering to such warm-blooded animal an effective amount of a compound of formula (I)

• a stereochemically isomeric form thereof, an N-oxide form thereof, a pharmaceutically acceptable acid addition salt thereof, or a quaternary ammonium salt thereof, wherein -a1=a2-a3=a4- is a bivalent radical of formula
• —N═CH—CH═CH— (a-1),
• —CH═N—CH═CH— (a-2),
• —CH═CH—N═CH— (a-3),
• —CH═CH—CH═N— (a-4),
• —N═N—CH═CH— (a-5),
• —N═CH—N═CH— (a-6),
• —N═CH—CH═N— (a-7),
• —CH═N—N═CH— (a-8),
• —CH═N—CH═N— (a-9), or
• —CH═CH—N═N— (a-10);
• -Z1-Z2- is a bivalent radical of formula
• —Y1—CH(R4)—CH2— (b-1),
• —Y1—CH(R4)—O— (b-2),
• —Y1—CH(R4)—CH2—O— (b-3),
• —Y1—CH(R4)—CH2—S— (b-4),
• —Y1—CH(R4)—CH2—NH— (b-5),
• —Y1—CH(R4)—CH2—CH2— (b-6),
• —Y1—CH(R4)—CH2—CH2—CH2— (b-7),
• —Y1—C(R4)═CH— (b-8),
• —Y1—C(R4)═CH—CH2— (b-9),
• —Y1—CH(R4)—CH═CH— (b-10), or
• —Y1—C(R4)═CH—CH2—CH2— (b-11), or
• —Y1—CH2—CH(R4)— (b-12),
• wherein, where possible, optionally one or two hydrogen atoms on the same or a different carbon or nitrogen atom may be replaced by hydroxy, C1-4alkyloxyC1-4alkyl, C1-4alkylcarbonyl, or C1-6alkyl optionally substituted with halo, hydroxy, C3-6cycloalkyl or phenyl;
• Y1 is oxygen or sulfur;
• Alk1 is C1-4alkylcarbonyl, carbonylC1-4alkyl, C1-4alkylcarbonylC1-4alkyl, carbonyl, or C1-6alkanediyl optionally substituted with hydroxy, halo, amino, hydroxyC1-4alkyl, C1-4alkyloxy, hydroxycarbonyl, C1-4alkyloxycarbonyl, aminocarbonyl, mono- or di(C1-4alkyl)aminocarbonyl, C1-4alkyloxyC1-4alkyl, C1-4alkylcarbonyloxy, C1-4alkylcarbonyloxyC1-4alkyloxycarbonyloxy, C1-4alkyloxyimino, phenylC1-4alkylamino, C1-4alkyloxycarbonylC1-6alkenyl, cyanoC1-6alkenyl or C1-6cycloalkylcarbonyloxyC1-4alkyloxycarbonyloxy;
• R1, R2 and R3 are each independently selected from hydrogen, C1-6alkyl, C3-6alkenyl, C1-6alkyloxy, hydroxycarbonyl, trihalomethyl, trihalomethoxy, halo, hydroxy, cyano, nitro, amino, C1-6alkylcarbonylamino, C1-6alkyloxycarbonyl, C1-4alkylcarbonyloxy, aminocarbonyl, mono- or di(C1-6alkyl)aminocarbonyl, aminoC1-6alkyl, mono- or di(C1-6alkyl)aminoC1-6alkyl, C1-4alkylcarbonyloxyC1-4alkyloxy-carbonyloxy, or C3-6cycloalkylcarbonyloxyC1-4alkyloxycarbonyloxy;
• R4 is hydrogen, hydroxycarbonyl, phenyl, aminocarbonyl, mono- or di(C1-4alkyl)aminocarbonyl, C1-4alkyloxyC1-4alkyl, C1-4alkyloxycarbonyl, N-pyrolidinylcarbonyl, N-piperidinylcarbonyl, N-homopiperidinylcarbonyl, C1-4alkylcarbonyloxyC1-4alkyloxycarbonyl, C1-4alkyloxycarbonylC1-4alkyl, C3-6cycloalkylcarbonyloxyC1-4alkyloxycarbonyloxy, or C1-6alkyl optionally substituted with hydroxy, cyano, amino, phenyl, mono- or di(C1-4alkyl)amino, or mono- or di(C1-4alkyl)aminocarbonyl;
• -A- is a bivalent radical of formula
• wherein m is 0 or 1;
• Alk2 is a bivalent radical independently selected from C1-4alkylcarbonylC1-4alkyl;
• phenyl;
• C3-6cycloalkylcarbonyloxyC1-4alkyloxycarbonyloxy;
• C3-8cycloalkanediyl optionally substituted with one or more halo, hydroxy, hydroxycarbonyl, hydroxyC1-4alkyl, C1-4alkyloxy, C1-4alkyloxyC1-4alkyl, C1-4alkyloxycarbonyl, C1-4alkylcarbonyloxyC1-4alkyloxycarbonyloxy, C3-6cycloalkylcarbonyloxyC1-4alkyloxycarbonyloxy, phenyl;
• or
• C1-6alkyl optionally substituted with one or more hydroxy, halo, amino, hydroxycarbonyl, hydroxyC1-4alkyl, C1-4alkyloxy, C1-4alkyloxyC1-4alkyl, C1-4alkyloxycarbonyl, C1-4alkylcarbonyloxyC1-4alkyloxycarbonyloxy, C3-6cycloalkyl, aminocarbonyl, mono- or di(C1-4alkyl)aminocarbonyl, or C1-6alkyl wherein the C1-6alkyl together with the carbon atom to which it is attached may form a C3-6cycloalkyl;
• R6 is hydrogen, C1-4alkyl, halo, hydroxy, hydroxyC1-4alkyl, C1-4alkyloxy, aminoC1-4 alkyl, C1-4alkyloxycarbonyl, C1-4alkylcarbonyloxyC1-4alkyloxy-carbonyl, amino, hydroxycarbonyl, aminocarbonyl, mono- or di(C1-4alkyl)aminocarbonyl, or C3-6cycloalkylcarbonyloxyC1-4alkyloxycarbonyloxy;
• R5 is a radical of formula
• wherein n is 1 or 2;
• P1 is 0, and p2 is 1 or 2;
• or p1 is 1 or 2, and p2 is 0;
• X is oxygen, sulfur, NR9 or CHNO2;
• Y2 is oxygen or sulfur;
• R7 is hydrogen, C1-16alkyl, C3-6cycloalkyl, phenyl or phenylmethyl;
• R8 is C1-6alkyl, C3-6cycloalkyl, phenyl or phenylmethyl;
• R9 is cyano, C1-6alkyl, C3-6cycloalkyl, C1-6alkyloxycarbonyl or aminocarbonyl;
• R10 is hydrogen or C1-6alkyl;
• or R9 and R10 taken together with the nitrogen atom to which they are attached may form a pyrrolidinyl, piperidinyl, homopiperidinyl, piperazinyl, or morpholinyl group, optionally substituted with C1-4alkyl or C1-4alkyloxy;
• and
• Q is a bivalent radical of formula
• —CH2—CH2— (e-1),
• —CH2—CH2—CH2— (e-2),
• —CH2—CH2—CH2—CH2— (e-3),
• —CH═CH— (e-4),
• —CH2—CO— (e-5),
• —CO—CH2— (e-6),
• —(CH2)2—CO— (e-7),
• —CO—(CH2)2— (e-8),
• —CO—CH2—CO— (e-9),
• —CH2—CO—CH2— (e-10),
• wherein optionally one or two hydrogen atoms on the same or a different carbon atom may be replaced by C1-4alkyl, hydroxy or phenyl, or
• Q is a bivalent radical of formula

A method according to claim II wherein wherein the bivalent radical -a1=a2-a3=a4- is of formula (a-1), (a-2) or (a-4);

• the bivalent radical -Z1-Z2- is of formula (b-1), (b-2) or (b-4) wherein;
• R4 is hydrogen;
• Alk1 is —CH2—;
• the bivalent radical -A- is of formula (c-2) wherein R6 is hydroxymethyl;
• and R5 is a radical of formula (d-1) wherein X is oxygen, R7 is hydrogen, and Q is (e-1), (e-2), (e-5) or (e-7).

A method according to claim II wherein the bivalent radical -a1=a2-a3=a4- is of formula (a-1), (a-2) or (a-4);

• the bivalent radical -Z1-Z2- is of formula (b-1), (b-2) or (b-4) wherein R4 is hydrogen;
• Alk1 is —CH2—;
• the bivalent radical -A- is of formula —CH2—CHOH—CH2—;
• and R5 is a radical of formula (d-1) wherein X is oxygen, R7 is hydrogen, and Q is (e-1), (e-2), (e-5) or (e-7).

A method as claimed in claim II wherein the compound is

• 1-[1-[(2,3-dihydro[1,4]dioxino[2,3-b]pyridin-3-yl)methyl]-4-piperidinyl]-2-imidazolidinone;
• 1-[1-[(2,3-dihydro[1,4]dioxino[2,3-b]pyridin-3-yl)methyl]-4-piperidinyl]tetrahydro-2(1H)-pyrimidinone;
• 1-[3-[[(2,3-dihydro[1,4]dioxino[2,3-b]pyridin-3-yl)methyl]amino]propyl]dihydro-2,4(1H,3H)-pyrimidinedione;
• and
• 1-[3-[[(2,3-dihydro[1,4]dioxino[2,3-b]pyridin-3-yl)methyl]amino]propyl]-2,4-imidazolidinedione, a pharmaceutically acceptable acid addition salt, a stereochemically isomeric form, or an N-oxide form thereof.