Compounds having effects on serotonin-related systems

A method of antagonizing or partially agonizing the serotonin 1A receptor which comprises administering to a subject in need of such treatment an effective amount of a compound of the formula ##STR49## wherein r is 0-4;

• s is 0-1;
• D is a residue which combines with the carbon atoms to which it is attached to complete a pyridinyl group;
• wherein X is hydrogen, phenyl, hydroxy or methoxy;
• provided that X is hydrogen or phenyl when r is 0;
• R is ##STR50## A is a residue which combines with the nitrogen atom to which it is attached to complete ##STR51## M is a residue which combines with the carbon atom to which it is attached to complete an indanyl, idenyl, pyrrolidinyl, tetralinyl, benzopyranyl, dihydroinndolyl, naphthodihydrofuranyl, benzodihydrothienyl, benzodihydrofuranyl, benzodihydropyranyl, naphthodihydrothienyl, or naphthodihydropyrrolyl group wherein the spiro junction is not to an aromatic ring,
• wherein M is substituted with 0-2 C.sub.1 -C.sub.3 alkyl, oxo, C.sub.1 -C.sub.3 alkoxy, pyrrolidinyl- or piperidinyl-C.sub.1 -C.sub.3 alkoxy, C.sub.1 -C.sub.2 alkylenedioxy, phenoxy, benzyloxy, phenyl or halo groups;
• p represents 0-2;
• R.sup.6 and R.sup.7 independently represent phenyl groups, substituted with 0-2 C.sub.1 -C.sub.3 alkyl, C.sub.1 -C.sub.3 alkoxy or halo
• q represents 0-2;
• Q represents a residue which combines with the atoms to which it is attached to complete a phenyl or naphthyl group, substituted with 0-2 C.sub.1 -C.sub.3 alkyl, C.sub.1 -C.sub.3 alkoxy or halo groups;
• or a pharmaceutically acceptable salt thereof.

A method of preventing or alleviating the symptoms caused by withdrawal or partial withdrawal from the use of tobacco or of nicotine which comprises administering to a subject in need of such treatment an effective amount of a compound of formula XII ##STR52## wherein r is 0-4;

• s is 0-1;
• D is a residue which combines with the carbon atoms to which it is attached to complete a pyridinyl group;
• wherein X is hydrogen, phenyl, hydroxy or methoxy;
• provided that X is hydrogen or phenyl when r is 0;
• R is ##STR53## A is a residue which combines with the nitrogen atom to which it is attached to complete ##STR54## M is a residue which combines with the carbon atom to which it is attached to complete an indanyl, idenyl, pyrrolidinyl, tetralinyl, benzopyranyl, dihydroinndolyl, naphthodihydrofuranyl, benzodihydrothienyl, benzodihydrofuranyl, benzodihydropyranyl, naphthodihydrothienyl, or naphthodihydropyrrolyl group wherein the spiro junction is not to an aromatic ring,
• wherein M is substituted with 0-2 C.sub.1 -C.sub.3 alkyl, oxo, C.sub.1 -C.sub.3 alkoxy, pyrrolidinyl- or piperidinyl-C.sub.1 -C.sub.3 alkoxy, C.sub.1 -C.sub.2 alkylenedioxy, phenoxy, benzyloxy, phenyl or halo groups;
• p represents 0-2;
• R.sup.6 and R.sup.7 independently represent phenyl groups, substituted with 0-2 C.sub.1 -C.sub.3 alkyl, C.sub.1 -C.sub.3 alkoxy or halo
• q represents 0-2;
• O represents a residue which combines with the atoms to which it is attached to complete a phenyl or naphthyl group, substituted with 0-2 C.sub.1 -C.sub.3 alkyl, C.sub.1 -C.sub.3 alkoxy or halo groups;
• or a pharmaceutically acceptable salt thereof.

A method of treating anxiety which comprises administering to a subject in need of such treatment an effective amount of a compound of formula XII ##STR55## wherein r is 0-4;

• s is 0-1;
• D is a residue which combines with the carbon atoms to which it is attached to complete a pyridinyl group;
• wherein X is hydrogen, phenyl, hydroxy or methoxy;
• provided that X is hydrogen or phenyl when r is 0;
• R is ##STR56## A is a residue which combines with the nitrogen atom to which it is attached to complete ##STR57## M is a residue which combines with the carbon atom to which it is attached to complete an indanyl, idenyl, pyrrolidinyl, tetralinyl, benzopyranyl, dihydroinndolyl, naphthodihydrofuranyl, benzodihydrothienyl, benzodihydrofuranyl, benzodihydropyranyl, naphthodihydrothienyl, or naphthodihydropyrrolyl group wherein the spiro junction is not to an aromatic ring,
• wherein M is substituted with 0-2 C.sub.1 -C.sub.3 alkyl, oxo, C.sub.1 -C.sub.3 alkoxy, pyrrolidinyl- or piperidinyl-C.sub.1 -C.sub.3 alkoxy, C.sub.1 -C.sub.2 alkylenedioxy, phenoxy, benzyloxy, phenyl or halo groups;
• p represents 0-2;
• R.sup.6 and R.sup.7 independently represent phenyl groups, substituted with 0-2 C.sub.1 -C.sub.3 alkyl, C.sub.1 -C.sub.3 alkoxy or halo
• q represents 0-2;
• O represents a residue which combines with the atoms to which it is attached to complete a phenyl or naphthyl group, substituted with 0-2 C.sub.1 -C.sub.3 alkyl, C.sub.1 -C.sub.3 alkoxy or halo groups;
• or a pharmaceutically acceptable salt thereof.

A method of treating a condition chosen from the group consisting of hypertension, cognitive disorders, sleep disorders, gastric motility disorders, sexual dysfunction, brain trauma, memory loss, eating disorders and obesity, substance abuse, obsessive-compulsive disease, panic disorder and migraine, comprising administering to a subject in need of such treatment an effective amount of a compound of formula XII ##STR58## wherein r is 0-4;

• s is 0-1;
• D is a residue which combines with the carbon atoms to which it is attached to complete a pyridinyl group;
• wherein X is hydrogen, phenyl, hydroxy or methoxy;
• provided that X is hydrogen or phenyl when r is 0;
• R is ##STR59## A is a residue which combines with the nitrogen atom to which it is attached to complete ##STR60## M is a residue which combines with the carbon atom to which it is attached to complete an indanyl, idenyl, pyrrolidinyl, tetralinyl, benzopyranyl, dihydroinndolyl, naphthodihydrofuranyl, benzodihydrothienyl benzodihydrofuranyl, benzodihydropyranyl, naphthodihydrothienyl, or naphthodihydropyrrolyl group wherein the spiro junction is not to an aromatic ring,
• wherein M is substituted with 0-2 C.sub.1 -C.sub.3 alkyl, oxo, C.sub.1 -C.sub.3 alkoxy, pyrrolidinyl- or piperidinyl-C.sub.1 -C.sub.3 alkoxy, C.sub.1 -C.sub.2 alkylenedioxy, phenoxy, benzyloxy, phenyl or halo groups;
• p represents 0-2;
• R.sup.6 and R.sup.7 independently represent phenyl groups, substituted with 0-2 C.sub.1 -C.sub.3 alkyl, C.sub.1 -C.sub.3 alkoxy or halo
• q represents 0-2;
• O represents a residue which combines with the atoms to which it is attached to complete a phenyl or naphthyl group, substituted with 0-2 C.sub.1 -C.sub.3 alkyl, C.sub.1 -C.sub.3 alkoxy or halo groups;
• or a pharmaceutically acceptable salt thereof.

A method of potentiating the action of a serotonin reuptake inhibitor in increasing the availability of serotonin, norepinephrine and dopamine in the brain, comprising administering to a subject in need of such treatment a serotonin reuptake inhibitor in combination with a method of antagonizing or partially agonizing the serotonin 1A receptor which comprises administering to a subject in need of such treatment an effective amount of a compound of the formula ##STR61## wherein r is 0-4;

• s is 0-1;
• D is a residue which combines with the carbon atoms to which it is attached to complete a pyridinyl group;
• wherein X is hydrogen, phenyl, hydroxy or methoxy;
• provided that X is hydrogen or phenyl when r is 0;
• R is ##STR62## A is a residue which combines with the nitrogen atom to which it is attached to complete ##STR63## M is a residue which combines with the carbon atom to which it is attached to complete an indanyl, idenyl, pyrrolidinyl, tetralinyl, benzopyranyl, dinhydroinndolyl, naphthodihydrofuranyl, benzodihydrothienyl, benzodihydrofuranyl, benzodihydropyranyl, naphthodihydrothienyl, or naphthodihydropyrrolyl group wherein the spiro junction is not to an aromatic ring,
• wherein M is substituted with 0-2 C.sub.1 -C.sub.3 alkyl, oxo, C.sub.1 -C.sub.3 alkoxy, pyrrolidinyl- or piperidinyl-C.sub.1 -C.sub.3 alkoxy, C.sub.1 -C.sub.2 alkylenedioxy, phenoxy, benzyloxy, phenyl or halo groups;
• p represents 0-2;
• R.sup.6 and R.sup.7 independently represent phenyl groups, substituted with 0-2 C.sub.1 -C.sub.3 alkyl, C.sub.1 -C.sub.3 alkoxy or halo
• q represents 0-2;
• O represents a residue which combines with the atoms to which it is attached to complete a phenyl or naphthyl group, substituted with 0-2 C.sub.1 -C.sub.3 alkyl, C.sub.1 -C.sub.3 alkoxy or halo groups;
• or a pharmaceutically acceptable salt thereof.