US20040127502A1 - Use of GAL3 antagonist for treatment of depression - Google Patents

Use of GAL3 antagonist for treatment of depression Download PDF

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US20040127502A1
US20040127502A1 US10/723,961 US72396103A US2004127502A1 US 20040127502 A1 US20040127502 A1 US 20040127502A1 US 72396103 A US72396103 A US 72396103A US 2004127502 A1 US2004127502 A1 US 2004127502A1
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heteroaryl
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Thomas Blackburn
Michael Konkel
Lakmal Boteju
Ian Talisman
John Wetzel
Mathivana Packiarajan
Heidi Chen
Hermo Jimenez
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H Lundbeck AS
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Synaptic Pharmaceutical Corp
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Priority claimed from US10/066,175 external-priority patent/US20030078271A1/en
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Priority to US10/723,961 priority Critical patent/US20040127502A1/en
Publication of US20040127502A1 publication Critical patent/US20040127502A1/en
Assigned to H. LUNDBECK A/S reassignment H. LUNDBECK A/S ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: SYNAPTIC PHARMACEUTICAL CORPORATION
Priority to US11/517,589 priority patent/US7465750B2/en
Priority to US12/314,675 priority patent/US20090318504A1/en
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Definitions

  • Depression is the most common of mental disorders and yet is often underdiagnosed and undertreated, inflicting substantial morbidity and psychosocial impairment on its sufferers. Depression is mainly characterized by sadness, flatness, loss of feeling, anhedonia (lack of pleasure), tearfulness, agitation or retardation, thoughts of guilt, and worthlessness; in severe cases, suicide, hallucinations and delusions.
  • Depression can be mainly categorized into bipolar disorders, identifying wide swings of mood; major depressive illness, marked by severe depressive symptoms but without manic swings; and less defined milder forms of bipolar and major depression that fall short of the specific diagnostic criteria e.g. dysthymic disorder (formerly called depressive neurosis).
  • the symptomatology and diagnostic criteria for depression are set out in the DSMIV guidelines (American Psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders). Although many patients have single episodes of major depressive illness, the condition also can be repetitive, and this recurrent condition is frequently called unipolar depressive illness.
  • depressive illness a markedly gloomy mood in which there is a loss of interest in life, and general feelings of hopelessness and worthlessness.
  • Depressive symptoms range in severity from mild mood swings to severe delusions about self-worth, accomplishments, and the future.
  • the key clinical features of anxiety disorders relate to various combinations of psychological and physical manifestations of anxiety, not attributable to real danger and occurring either in attacks (panic disorder PD) or as a persisting state (generalized anxiety disorder -GAD).
  • Other neurotic features may be present (obsessional or hysterical symptoms) but do not dominate the clinical picture.
  • TCAs tricylic antidepressants
  • SSRIs selective serotonin re-uptake inhibitors
  • MAOIs monoamine oxidase inhibitors
  • This theory postulates that a certain level of amines and/or receptor sensitivity to catecholamines functions to generate a normal mood.
  • a receptor insensitivity, a depletion of monoamines, or a decrease in their release, synthesis or storage have been postulated to lead to depression.
  • a variety of pharmacological agents have been employed to treat depression based on the catecholamine-indolamine hypothesis of depression.
  • Drugs used to treat depression include MAOIs, atypical antipsychotics, lithium, TCAs, and SSRIs.
  • off-label agents such as antiepileptics are used to treat depression in treatment-resistant patients.
  • Tricyclic antidepressants are about equal to SSRIs in effectiveness against depression thus providing supporting evidence for the catecholamine-indolamine hypothesis of depression.
  • SSRIs have largely displaced TCAs because of side effects associated with TCAs and the need to monitor EKG and plasma drug concentration.
  • Adverse effects on sexual function primarily anorgasmia and delayed ejaculation, have been consistently reported.
  • Other, common side-effects include sleep disorders, yawning, weight changes, suicidal ideation and extrapyramidal-like side-effects such as dystonic reactions.
  • OCD obsessive compulsive disorder
  • GAD generalized anxiety disorder
  • PD panic disorder
  • GAL3 receptor may play a role in controlling the activity of catecholamine and indolamine neurons in the CNS.
  • Galanin is known to hyperpolarize neurons, including monoaminergic neurons (Seutin, et al., 1989) and to have inhibitory effects on 5-HT neurons (Xu, et al., 1998), and dopamine neurons (Gopalan, et al., 1993; De Weille, et al., 1989; Jansson, et al., 1989; Nordstrom, et al., 1987; Weiss, et al., 1998).
  • the rat Forced Swim Test is a behavioral test that is used to screen compounds for antidepressant efficacy (Porsolt et al., 1977, 1978; Porsolt, 1981). This test is widely used as it is reliable across laboratories, relatively easy to perform and is sensitive to the effects of some of the major classes of antidepressant drugs, including TCAs and MAOIs, and various atypical antidepressants. Furthermore, this test is relatively selective for antidepressant drugs, as few psychoactive drugs produce similar behavioral actions in the FST.
  • SIT Social Interaction Test
  • rats previously housed singly are placed in a familiar, dimly lit, test arena with weight-matched, novel partners.
  • the principal anxiogenic stimulus under these conditions is the partner novelty, which involves an unconditioned response to a potential threat.
  • the following behaviors are scored as active social interaction: grooming, sniffing, biting, boxing, wrestling, following, crawling over and crawling under.
  • the synthesis of novel pyrimidines which bind selectively to the cloned human GAL3 receptor, compared to other cloned human G-protein coupled receptors, as measured in in vitro assays is disclosed.
  • the synthesis of indolones which bind selectively to the cloned human GAL3 receptor, compared to other cloned human G-protein coupled receptors, as measured in in vitro assays is disclosed.
  • the in vitro receptor assays described hereinafter were performed using various cultured cell lines, each transfected with and expressing only a single galanin-type receptor.
  • the present invention provides a method of treating a subject suffering from depression which comprises administering to the subject an amount of compound effective to treat the subject's depression wherein the compound has the structure:
  • W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
  • R 11 is H, straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , aryl, or aryl (C 1 -C 6 )alkyl;
  • R 12 is straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , or —(CH 2 ) m —Z;
  • R 13 is a bicyclic alkyl ring system, adamantyl, noradamantyl, C 3 -C 10 cycloalkyl, heteroaryl, aryl, aryl(C 1 -C 6 )alkyl, Q 1 or Q 2 ;
  • aryl may be substituted with one or more C 1 -C 10 straight chained or branched alkyl, aryl, heteroaryl, or N(R 19 )—Z;
  • each J is independently O, S, C(R 22 ) 2 or NR 4 ;
  • R 4 is H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl or aryl;
  • R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • R 15 is straight chained or branched C 3 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, (C(R 19 ) 2 ) m N(R 16 ) 2 or (C(R 19 ) 2 ) m —Z;
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • R 18 is straight chained or branched C 1 -C 6 alkyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl
  • each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl, or aryl(C 1 -C 6 ) alkyl;
  • each R 22 is independently H, F, Cl or C 1 -C 4 straight chained or branched alkyl
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
  • Z is C 3 -C 10 cycloalkyl, C 4 -C 7 cyclic ether, C 4 -C 7 cyclic thioether, aryl, or heteroaryl; or
  • the present invention provides a method of treating a subject suffering from depression which comprises administering to the subject an amount of compound effective to treat the subject's depression wherein the compound has the structure:
  • W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
  • R 11 is H, straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , aryl or aryl(C 1 -C 6 )alkyl;
  • R 12 is straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , or —(CH 2 ) m —Z;
  • R 13 is a bicyclic alkyl ring system, aryl or aryl (C 1 -C 6 ) alkyl;
  • R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • R 15 is straight chained or branched C 3 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
  • Z is C 3 -C 10 cycloalkyl, aryl, or heteroaryl
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • R 18 is straight chained or branched C 1 -C 6 alkyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl
  • each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 ) alkyl;
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • the present invention provides a method of treating a subject suffering from depression which comprises administering to the subject an amount of compound effective to treat the subject's depression wherein the compound has the structure:
  • W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
  • R 13 is an aryl, adamantyl, noradamantyl, C 3 -C 10 cycloalkyl, heteroaryl, Q 1 or Q 2 ;
  • aryl may be substituted with one or more C 1 -C 10 straight chained or branched alkyl, aryl, heteroaryl, or N(R 19 )—Z;
  • each J is independently O, S, C(R 22 ) 2 or NR 4 ;
  • R 4 is —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl or aryl;
  • R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • R 15 is straight chained or branched C 3 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
  • Z is C 3 -C 10 cycloalkyl, aryl, or heteroaryl
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • R 18 is straight chained or branched C 1 -C 6 alkyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl
  • each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 ) alkyl;
  • each R 22 is independently H, F, Cl or C 1 -C 4 straight chained or branched alkyl
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • the present invention provides a method of treating a subject suffering from depression which comprises administering to the subject an amount of compound effective to treat the subject's depression wherein the compound has the structure:
  • W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
  • R 13 is a bicyclic alkyl ring system, aryl or aryl (C 1 -C 6 )alkyl;
  • R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • R 15 is (C(R 19 ) 2 ) m —N(R 16 ) 2 ;
  • Z is C 3 -C 10 cycloalkyl, aryl, or heteroaryl
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • the present invention also provides a method of treating a subject suffering from anxiety which comprises administering to the subject an amount of compound effective to treat the subject's anxiety wherein the compound has the structure:
  • W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
  • R 11 is H, straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , aryl, or aryl (C 1 -C 6 )alkyl;
  • R 12 is straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , or —(CH 2 ) m —Z;
  • R 13 is a bicyclic alkyl ring system, adamantyl, noradamantyl, C 3 -C 10 cycloalkyl, heteroaryl, aryl, aryl(C 1 -C 6 )alkyl, Q 1 or Q 2 ;
  • aryl may be substituted with one or more C 1 -C 10 straight chained or branched alkyl, aryl, heteroaryl, or N(R 19 )—Z;
  • each J is independently O, S, C(R 22 ) 2 or NR 4 ;
  • R 4 is H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl or aryl;
  • R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • R 15 is straight chained or branched C 3 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, (C(R 19 ) 2 ) m N(R 16 ) 2 or (C(R 19 ) 2 ) m —Z
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • R 18 is straight chained or branched C 1 -C 6 alkyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl
  • each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl, or aryl(C 1 -C 6 )alkyl;
  • each R 22 is independently H, F, Cl or C 1 -C 4 straight chained or branched alkyl
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
  • Z is C 3 -C 10 cycloalkyl, C 4 -C 7 cyclic ether, C 4 -C 7 cyclic thioether, aryl, or heteroaryl; or
  • the invention provides a method of treating a subject suffering from anxiety which comprises administering to the subject an amount of compound effective to treat the subject's anxiety wherein the compound has the structure:
  • W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
  • R 11 is H, straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , aryl or aryl(C 1 -C 6 ) alkyl;
  • R 12 is straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , or —(CH 2 ) m —Z;
  • R 13 is a bicyclic alkyl ring system, aryl or aryl(C 1 -C 6 )alkyl;
  • R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • R 15 is straight chained or branched C 3 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
  • Z is C 3 -C 10 cycloalkyl, aryl, or heteroaryl
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • R 18 is straight chained or branched C 1 -C 6 alkyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl
  • each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • the invention provides a method of treating a subject suffering from anxiety which comprises administering to the subject an amount of compound effective to treat the subject's anxiety wherein the compound has the structure:
  • W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
  • R 13 is an aryl, adamantyl, noradamantyl, C 3 -C 10 cycloalkyl, heteroaryl, Q 1 or Q 2 ;
  • aryl may be substituted with one or more C 1 -C 10 straight chained or branched alkyl, aryl, heteroaryl, or N(R 19 )—Z;
  • each J is independently O, S, C(R 22 ) 2 or NR 4 ;
  • R 4 is —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl or aryl;
  • R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • R 15 is straight chained or branched C 3 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
  • Z is C 3 -C 10 cycloalkyl, aryl, or heteroaryl
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • R 18 is straight chained or branched C 1 -C 6 alkyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl
  • each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
  • each R 22 is independently H, F, Cl or C 1 -C 4 straight chained or branched alkyl
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • the invention provides a method of treating a subject suffering from anxiety which comprises administering to the subject an amount of compound effective to treat the subject's anxiety wherein the compound has the structure:
  • W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
  • R 13 is a bicyclic alkyl ring system, aryl or aryl(C 1 -C 6 )alkyl;
  • R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • R 15 is (C(R 19 ) 2 ) m —N(R 16 ) 2 ;
  • Z is C 3 -C 10 cycloalkyl, aryl, or heteroaryl
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • the invention also provides a pharmaceutical composition
  • a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound having the structure:
  • W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
  • R 11 is H, straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , aryl, or aryl (C 1 -C 6 )alkyl;
  • R 12 is straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , or —(CH 2 ) m —Z;
  • R 13 is a bicyclic alkyl ring system, adamantyl, noradamantyl, C 3 -C 10 cycloalkyl, heteroaryl, aryl, aryl(C 1 -C 6 )alkyl, Q 1 or Q 2 ;
  • aryl may be substituted with one or more C 1 -C 10 straight chained or branched alkyl, aryl, heteroaryl, or N(R 19 )—Z;
  • each J is independently O, S, C(R 22 ) 2 or, NR 4 ;
  • R 4 is H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl or aryl;
  • R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • R 15 is straight chained or branched C 3 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, (C(R 19 ) 2 ) m N(R 16 ) 2 or (C(R 19 ) 2 ) m —Z;
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • R 18 is straight chained or branched C 1 -C 6 alkyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl
  • each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR21, —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl, or aryl(C 1 -C 6 ) alkyl;
  • each R 22 is independently H, F, Cl or C 1 -C 4 straight chained or branched alkyl
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
  • Z is C 3 -C 10 cycloalkyl, C 4 -C 7 cyclic ether, C 4 -C 7 cyclic thioether, aryl, or heteroaryl; or
  • the invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound having the structure:
  • W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
  • R 11 is H, straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , aryl or aryl(C 1 -C 6 )alkyl;
  • R 12 is straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , or —(CH 2 ) m —Z;
  • R 13 is a bicyclic alkyl ring system, aryl or aryl (C 1 -C 6 ) alkyl;
  • R 14 is straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
  • Z is C 3 -C 10 cycloalkyl, aryl, or heteroaryl
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • R 18 is straight chained or branched C 1 -C 6 alkyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl
  • each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 ) alkyl;
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • the invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound having the structure:
  • W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
  • R 13 is an aryl, adamantyl, noradamantyl, C 3 -C 10 cycloalkyl, heteroaryl, Q 1 or Q 2 ;
  • aryl may be substituted with one or more C 1 -C 10 straight chained or branched alkyl, aryl, heteroaryl, or N(R 19 )—Z;
  • each J is independently O, S, C(R 22 ) 2 or NR 4 ;
  • R 4 is —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl or aryl;
  • R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • R 15 is straight chained or branched C 3 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
  • Z is C 3 -C 10 cycloalkyl, aryl, or heteroaryl
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • R 18 is straight chained or branched C 1 -C 6 alkyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl
  • each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 ) alkyl;
  • each R 22 is independently H, F, Cl or C 1 -C 4 straight chained or branched alkyl
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • the invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound having the structure:
  • W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
  • R 13 is a bicyclic alkyl ring system, aryl or aryl (C 1 -C 6 ) alkyl;
  • R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • R 15 is (C(R 19 ) 2 ) m —N(R 16 ) 2 ;
  • Z is C 3 -C 10 cycloalkyl, aryl, or heteroaryl
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, (CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 ) alkyl;
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • the invention provides a compound having the structure:
  • W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
  • R 11 is H, straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , aryl, or aryl (C 1 -C 6 )alkyl;
  • R 12 is straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , or —(CH 2 ) m —Z;
  • R 13 is a bicyclic alkyl ring system, adamantyl, noradamantyl, C 3 -C 10 cycloalkyl, heteroaryl, aryl, aryl(C 1 -C 6 )alkyl, Q 1 or Q 2 ;
  • aryl may be substituted with one or more C 1 -C 10 straight chained or branched alkyl, aryl, heteroaryl, or N(R 19 )—Z;
  • each J is independently O, S, C(R 22 ) 2 or NR 4 ;
  • R 4 is H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl or aryl;
  • R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • R 15 is straight chained or branched C 3 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, (C(R 19 ) 2 ) m N(R 16 ) 2 or (C(R 19 ) 2 ) m —Z;
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 17 is independently H; —OR 21 , —OCOR 21 —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • R 18 is straight chained or branched C 1 -C 6 alkyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl
  • each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl, or aryl(C 1 -C 6 ) alkyl;
  • each R 22 is independently H, F, Cl or C 1 -C 4 straight chained or branched alkyl
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
  • Z is C 3 -C 10 cycloalkyl, C 4 -C 7 cyclic ether, C 4 -C 7 cyclic thioether, aryl, or heteroaryl; or
  • the invention provides a compound having the structure:
  • W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
  • R 11 is H, straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , aryl or aryl (C 1 -C 6 ) alkyl;
  • R 12 is straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , or —(CH 2 ) m —Z;
  • R 13 is a bicyclic alkyl ring system, aryl or aryl (C 1 -C 6 ) alkyl;
  • R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • R 15 is straight chained or branched C 3 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
  • Z is C 3 -C 10 cycloalkyl, aryl, or heteroaryl
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • R 18 is straight chained or branched C 1 -C 6 alkyl, (CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl
  • each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 ) alkyl;
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • the invention provides a compound having the structure:
  • W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
  • R 13 is an aryl, adamantyl, noradamantyl, C 3 -C 10 cycloalkyl, heteroaryl, Q 1 or Q 2 ;
  • aryl may be substituted with one or more C 1 -C 10 straight chained or branched alkyl, aryl, heteroaryl, or N(R 19 )—Z;
  • each J is independently O, S, C(R 22 ) 2 or NR 4 ;
  • R 4 is —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl or aryl;
  • R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • R 15 is straight chained or branched C 3 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
  • Z is C 3 -C 10 cycloalkyl, aryl, or heteroaryl
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • R 18 is straight chained or branched C 1 -C 6 alkyl, (CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl
  • each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
  • each R 22 is independently H, F, Cl or C 1 -C 4 straight chained or branched alkyl
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • the invention provides a compound having the structure:
  • W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
  • R 13 is a bicyclic alkyl ring system, aryl or aryl (C 1 -C 6 ) alkyl;
  • R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • R 15 is (C(R 19 ) 2 ) m —N(R 16 ) 2 ;
  • Z is C 3 -C 10 cycloalkyl, aryl, or heteroaryl
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained ox branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 ) alkyl;
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • the invention also provides a method of treating a subject suffering from depression which comprises administering to the subject an amount of compound effective to treat, the subject's depression wherein the compound has the structure:
  • each of Y 1 , Y 2 , Y 3 , and Y 4 is independently H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can constitute
  • each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl (C 1 -C 6 ) alkyl;
  • A is A′, Q 3 , Q 4 , Q 5 , straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 ) alkyl, heteroaryl (C 1 -C 6 ) alkyl, aryl substituted with an aryl or heteroaryl, heteroaryl substituted with an aryl or heteroaryl; or (CHR 17 )—(CHR 17 ) n —Z;
  • R 1 and R 2 are each independently H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , or —CN;
  • R 3 is H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , —CN, —OR 6 , aryl or heteroaryl;
  • R 5 is straight chained or branched C 1 -C 7 alkyl, —N(R 4 ) 2 , —OR 6 or aryl;
  • R 6 is straight chained or branched C 1 -C 7 alkyl or aryl
  • each R 17 is independently H; straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • each p is an integer from 0 to 2 inclusive;
  • U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
  • Z is C 3 -C 10 cycloalkyl, C 4 -C 7 cyclic ether, C 4 -C 7 cyclic thioether, aryl, or heteroaryl;
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • B is aryl, heteroaryl, aryl substituted with an aryl or heteroaryl, heteroaryl substituted with an aryl or heteroaryl, tricyclic heteroaryl or Q 6 ; provided however, if B is aryl or heteroaryl the carbon atom or carbon atoms ortho to the nitrogen atom of the imine bond may only be substituted with one or more of the following —F, —Cl, —Br, —I, —CN, methyl, ethyl or methoxy;
  • a tricyclic heteroaryl is a fused three member aromatic system in which one or more of the rings is heteroaryl; carbazole; or acridine;
  • each R 22 is independently H, F,
  • the invention provides a method of treating a subject suffering from depression which comprises administering to the subject an amount of compound effective to treat the subject's depression wherein the compound has the structure:
  • each of Y 1 , Y 2 , Y 3 , and Y 4 is independently H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can constitute a
  • each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
  • A is A′, straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl or heteroaryl (C 1 -C 6 )alkyl;
  • R 1 and R 2 are each independently H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, NO 2 , or —CN;
  • R 3 is H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , —CN, —OR 6 aryl or heteroaryl;
  • R 5 is straight chained or branched C 1 -C 7 alkyl, —N(R 4 ) 2 , —OR 6 or aryl;
  • R 6 is straight chained or branched C 1 -C 7 alkyl or aryl
  • B is aryl, or heteroaryl; provided however, if B is aryl or heteroaryl the carbon atom or carbon atoms ortho to the nitrogen atom of the imine bond may only be substituted with one or more of the following —F, —Cl, —Br, —I, —CN, methyl, ethyl or methoxy;
  • n is an integer from 1 to 4 inclusive
  • the invention provides a method of treating a subject suffering from depression which comprises administering to the subject an amount of compound effective to treat the subject's depression wherein the compound has the structure:
  • each of Y 1 , Y 2 , Y 3 , and Y 4 is independently H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN ; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can constitute
  • each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl (C 1 -C 6 ) alkyl;
  • A is A′, straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl or heteroaryl (C 1 -C 6 ) alkyl;
  • B is aryl substituted with an aryl or heteroaryl, heteroaryl substituted with an aryl or heteroaryl, tricyclic heteroaryl or Q 6 ;
  • a tricyclic heteroaryl is a fused three ring aromatic system in which one or more of the rings is heteroaryl; carbazole; or acridine;
  • n is an integer from 1 to 4 inclusive
  • each R 22 is independently H, F, Cl, or straight chained or branched C 1 -C 4 alkyl
  • the invention provides a method of treating a subject suffering from depression which comprises administering to the subject an amount of compound effective to treat the subject's depression wherein the compound has the structure:
  • each of Y 1 , Y 2 , Y 3 , and Y 4 is independently H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can constitute
  • each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
  • A is Q 3 , Q 4 , Q 5 , aryl substituted with an aryl or heteroaryl, heteroaryl substituted with an aryl or heteroaryl, or (CHR 17 )—(CHR 17 ) n —Z;
  • each R 17 is independently H; straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl;.
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl or aryl;
  • each R 22 is independently H, F, Cl, or straight chained or branched C 1 -C 4 alkyl
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • each p is an integer from 0 to 2 inclusive;
  • U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
  • Z is C 3 -C 10 cycloalkyl, C 4 -C 7 cyclic ether, C 4 -C 7 cyclic thioether, aryl, or heteroaryl;
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • B is aryl, or heteroaryl; provided however, if B is aryl or heteroaryl the carbon atom or carbon atoms ortho to the nitrogen atom of the imine bond may only be substituted with one or more of the following —F, —Cl, —Br, —I, —CN, methyl, ethyl or methoxy;
  • the invention provides a method of treating a subject suffering from anxiety which comprises administering to the subject an amount of compound effective to treat the subject's anxiety wherein the compound has the structure:
  • each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can
  • each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
  • A is A′, Q 3 , Q 4 , Q 5 , straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl, heteroaryl(C 1 -C 6 )alkyl, aryl substituted with an aryl or heteroaryl, heteroaryl substituted with an aryl or heteroaryl; or (CHR 17 )—(CHR 17 ) n —Z;
  • R 1 and R 2 are each independently H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , or —CN;
  • R 3 is H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , —CN, —OR 6 , aryl or heteroaryl;
  • R 5 is straight chained or branched C 1 -C 7 alkyl, —N(R 4 ) 2 , —OR 6 or aryl;
  • R 6 is straight chained or branched C 1 -C 7 alkyl or aryl
  • each R 17 is independently H; straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • each p is an integer from 0 to 2 inclusive;
  • U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
  • Z is C 3 -C 10 cycloalkyl, C 4 -C 7 cyclic ether, C 4 -C 7 cyclic thioether, aryl, or heteroaryl;
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • B is aryl, heteroaryl, aryl substituted with an aryl or heteroaryl, heteroaryl substituted with an aryl or heteroaryl, tricyclic heteroaryl or Q 6 ; provided however, if B is aryl or heteroaryl the carbon atom or carbon atoms ortho to the nitrogen atom of the imine bond may only be substituted with one or more of the following —F, —Cl, —Br, —I, —CN, methyl, ethyl or methoxy;
  • a tricyclic heteroaryl is a fused three member aromatic system in which one or more of the rings is heteroaryl; carbazole; or acridine;
  • each R 22 is independently H, F, Cl, or straight chained or branched C 1 -C 4 alkyl
  • the invention provides a method of treating a subject suffering from anxiety which comprises administering to the subject an amount of compound effective to treat the subject's anxiety wherein the compound has the structure:
  • each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can
  • each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
  • A is A′, straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl or heteroaryl (C 1 -C 6 ) alkyl;
  • R 1 and R 2 are each independently H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , or —CN;
  • R 3 is H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , —CN, —OR 6 aryl or heteroaryl;
  • R 5 is straight chained or branched C 1 -C 7 alkyl, —N(R 4 ) 2 , —OR 6 or aryl;
  • R 6 is straight chained or branched C 1 -C 7 alkyl or aryl
  • B is aryl, or heteroaryl; provided however, if B is aryl or heteroaryl the carbon atom or carbon atoms ortho to the nitrogen atom of the imine bond may only be substituted with one or more of the following —F, —Cl, —Br, —I, —CN, methyl, ethyl or methoxy;
  • n is an integer from 1 to 4 inclusive
  • the invention provides a method of treating a subject suffering from anxiety which comprises administering to the subject an amount of compound effective to treat the subject's anxiety wherein the compound has the structure:
  • each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can
  • each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
  • A is A′, straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl or heteroaryl (C 1 -C 6 ) alkyl;
  • B is aryl substituted with an aryl or heteroaryl, heteroaryl substituted with an aryl or heteroaryl, tricyclic heteroaryl or Q 6 ;
  • a tricyclic heteroaryl is a fused three ring aromatic system in which one or more of the rings is heteroaryl; carbazole; or acridine;
  • n is an integer from 1 to 4 inclusive
  • each R 22 is independently H, F,
  • the invention provides a method of treating a subject suffering from anxiety which comprises administering to the subject an amount of compound effective to treat the subject's anxiety wherein the compound has the structure:
  • each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can
  • each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
  • A is Q 3 , Q 4 , Q 5 , aryl substituted with an aryl or heteroaryl, heteroaryl substituted with an aryl or heteroaryl, or (CHR 17 )—(CHR 17 ) n —Z;
  • each R 17 is independently H; straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl or aryl;
  • each R 22 is independently H, F, Cl, or straight chained or branched C 1 -C 4 alkyl
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • each p is an integer from 0 to 2 inclusive;
  • U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
  • Z is C 3 -C 10 cycloalkyl, C 4 -C 7 cyclic ether, C 4 -C 7 cyclic thioether, aryl, or heteroaryl;
  • R 1 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • B is aryl, or heteroaryl; provided however, if B is aryl or heteroaryl the carbon atom or carbon atoms ortho to the nitrogen atom of the imine bond may only be substituted with one or more of the following —F, —Cl, —Br, —I, —CN, methyl, ethyl or methoxy;
  • the invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound having the structure:
  • each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can constitute
  • each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
  • A is A′, Q 3 , Q 4 , Q 5 , straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl, heteroaryl(C 1 -C 6 )alkyl, aryl substituted with an aryl or heteroaryl, heteroaryl substituted with an aryl or heteroaryl; or (CHR 17 )—(CHR 17 ) n —Z;
  • R 1 and R 2 are each independently H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , or —CN;
  • R 3 is H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , —CN, —OR 6 , aryl or heteroaryl;
  • R 5 is straight chained or branched C 1 -C 7 alkyl, —N(R 4 ) 2 , —OR 6 or aryl;
  • R 6 is straight chained or branched C 1 -C 7 alkyl or aryl
  • each R 17 is independently H; straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • each p is an integer from 0 to 2 inclusive;
  • U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
  • Z is C 3 -C 10 cycloalkyl, C 4 -C 7 cyclic ether, C 4 -C 7 cyclic thioether, aryl, or heteroaryl;
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • B is aryl, heteroaryl, aryl substituted with an aryl or heteroaryl, heteroaryl substituted with an aryl or heteroaryl, tricyclic heteroaryl or Q 6 ; provided however, if B is aryl or heteroaryl the carbon atom or carbon atoms ortho to the nitrogen atom of the imine bond may only be substituted with one or more of the following —F, —Cl, —Br, —I, —CN, methyl, ethyl or methoxy;
  • a tricyclic heteroaryl is a fused three member aromatic system in which one or more of the rings is heteroaryl; carbazole; or acridine;
  • each R 22 is independently H, F, Cl, or straight chained or branched C 1 -C 4 alkyl
  • the invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound having the structure:
  • each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can
  • each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl (C 1 -C 6 ) alkyl;
  • A is A′, straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl or heteroaryl (C 1 -C 6 ) alkyl;
  • R 1 and R 2 are each independently H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , or —CN;
  • R 3 is H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , —CN, —OR 6 aryl or heteroaryl;
  • R 5 is straight chained or branched C 1 -C 7 alkyl, —N(R 4 ) 2 , —OR 6 or aryl;
  • R 6 is straight chained or branched C 1 -C 7 alkyl or aryl
  • B is aryl, or heteroaryl; provided however, if B is aryl or heteroaryl the carbon atom or carbon atoms ortho to the nitrogen atom of the imine bond may only be substituted with one or more of the following —F, —Cl, —Br, —I, —CN, methyl, ethyl or methoxy;
  • n is an integer from 1 to 4 inclusive
  • the invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound having the structure:
  • each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can
  • each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
  • A is A′, straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl or heteroaryl (C 1 -C 6 ) alkyl;
  • B is aryl substituted with an aryl or heteroaryl, heteroaryl substituted with an aryl or heteroaryl, tricyclic heteroaryl or Q 6 ;
  • a tricyclic heteroaryl is a fused three ring aromatic system in which one or more of the rings is heteroaryl; carbazole; or acridine;
  • n is an integer from 1 to 4 inclusive
  • each R 22 is independently H, F,
  • the invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound having the structure:
  • each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can
  • each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl (C 1 -C 6 ) alkyl;
  • A is Q 3 , Q 4 , Q 5 , aryl substituted with an aryl or heteroaryl, heteroaryl substituted with an aryl or heteroaryl, or (CHR 17 )—(CHR 17 ) n —Z;
  • each R 17 is independently H; straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl or aryl;
  • each R 22 is independently H, F, Cl, or straight chained or branched C 1 -C 4 alkyl
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • each p is an integer from 0 to 2 inclusive;
  • U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
  • Z is C 3 -C 10 cycloalkyl, C 4 -C 7 cyclic ether, C 4 -C 7 cyclic thioether, aryl, or heteroaryl;
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • B is aryl, or heteroaryl; provided however, if B is aryl or heteroaryl the carbon atom or carbon atoms ortho to the nitrogen atom of the imine bond may only be substituted with one or more of the following —F, —Cl, —Br, —I, —CN, methyl, ethyl or methoxy;
  • the invention provides a compound having the structure:
  • each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 ; or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can
  • each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl (C 1 -C 6 ) alkyl;
  • A is A′, Q 3 , Q 4 , Q 5 , straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl, heteroaryl (C 1 -C 6 ) alkyl, aryl substituted with an aryl or heteroaryl, heteroaryl substituted with an aryl or heteroaryl; or (CHR 17 )—(CHR 17 ) n —Z;
  • R 1 and R 2 are each independently H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , or —CN;
  • R 3 is H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , —CN, —OR 6 , aryl or heteroaryl;
  • R 5 is straight chained or branched C 1 -C 7 alkyl, —N(R 4 ) 2 , —OR 6 or aryl;
  • R 6 is straight chained or branched C 1 -C 7 alkyl or aryl
  • each R 17 is independently H; straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • each p is an integer from 0 to 2 inclusive;
  • U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
  • Z is C 3 -C 10 cycloalkyl, C 4 -C 7 cyclic ether, C 4 -C 7 cyclic thioether, aryl, or heteroaryl;
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • B is aryl, heteroaryl, aryl substituted with an aryl or heteroaryl, heteroaryl substituted with an aryl or heteroaryl, tricyclic heteroaryl or Q 6 ; provided however, if B is aryl or heteroaryl the carbon atom or carbon atoms ortho to the nitrogen atom of the imine bond may only be substituted with one or more of the following —F, —Cl, —Br, —I, —CN, methyl, ethyl or methoxy;
  • a tricyclic heteroaryl is a fused three member aromatic system in which one or more of the rings is heteroaryl; carbazole; or acridine;
  • each R 22 is independently, H, F, Cl, or straight chained or branched C 1 -C 4 alkyl;
  • the invention provides a compound having the structure:
  • each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can
  • each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
  • A is A′, straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl or heteroaryl (C 1 -C 6 )alkyl;
  • R 1 and R 2 are each independently H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , or —CN;
  • R 3 is H, straight chained or branched C 1 -C 7 alkyl, —F, —Cl, —Br, —I, —NO 2 , —CN, —OR 6 aryl or heteroaryl;
  • R 5 is straight chained or branched C 1 -C 7 alkyl, —N(R 4 ) 2 , —OR 6 or aryl;
  • R 6 is straight chained or branched C 1 -C 7 alkyl or aryl
  • B is aryl, or heteroaryl; provided however, if B is aryl or heteroaryl the carbon atom or carbon atoms ortho to the nitrogen atom of the imine bond may only be substituted with one or more of the following —F, —Cl, —Br, —I, —CN, methyl, ethyl or methoxy;
  • n is an integer from 1 to 4 inclusive
  • the invention provides a compound having the structure:
  • each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; —OR any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atom
  • each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
  • A is A′, straight chained or branched C 1 -C 7 alkyl, aryl, heteroaryl, aryl(C 1 -C 6 )alkyl or heteroaryl(C 1 -C 6 )alkyl;
  • B is aryl substituted with an aryl or heteroaryl, heteroaryl substituted with an aryl or heteroaryl, tricyclic heteroaryl or Q 6 ;
  • a tricyclic heteroaryl is a fused three ring aromatic system in which one or more of the rings is heteroaryl; carbazole; or acridine;
  • n is an integer from 1 to 4 inclusive
  • each R 22 is independently H, F, Cl, or straight chained or branched C 1 -C 4 alkyl
  • the invention provides a compound having the structure:
  • each of Y 1 , Y 2 , Y 3 , and Y 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —SR 4 , —OCOR 4 , —COR 4 , —NCOR 4 , —N(R 4 ) 2 , —CON(R 4 ) 2 , or —COOR 4 ; aryl or heteroaryl; or any two of Y 1 , Y 2 , Y 3 and Y 4 present on adjacent carbon atoms can
  • each R 4 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
  • A is Q 3 , Q 4 , Q 5 , aryl substituted with an aryl or heteroaryl, heteroaryl substituted with an aryl or heteroaryl, or (CHR 17 )—(CHR 17 ) n —Z;
  • each R 17 is independently —H; straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl or aryl;
  • each R 22 is independently H, F, Cl, or straight chained or branched C 1 -C 4 alkyl
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • each p is an integer from 0 to 2 inclusive;
  • U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
  • Z is C 3 -C 10 cycloalkyl, C 4 -C 7 , cyclic ether, C 4 -C 7 cyclic thioether, aryl, or heteroaryl;
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • B is aryl, or heteroaryl; provided however, if B is aryl or heteroaryl the carbon atom or carbon atoms ortho to the nitrogen atom of the imine bond may only be substituted with one or more of the following —F, —Cl, —Br, —I, —CN, methyl, ethyl or methoxy;
  • the invention provides a method of treating depression in a subject which comprises administering to the subject a composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a GAL3 receptor antagonist, wherein:
  • the GAL3Receptor antagonist binds to the human GAL3 Receptor with a binding affinity at least ten-Fold higher than the binding affinity with which it binds to the human GAL1 receptor;
  • the GAL3Receptor antagonist does not inhibit the activity of central monoamine oxidase B greater than 50 percent, at a concentration of 10 ⁇ M;
  • the GAL3Receptor antagonist binds to the human GAL3Receptor with a binding affinity at least ten-fold higher than the binding affinity with which it binds to each of the following transporters: serotonin transporter, norepinephrine transporter, and dopamine transporter.
  • the invention provides a method of treating anxiety in a subject which comprises administering to the subject a composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a GAL3 receptor antagonist, wherein:
  • the GAL3Receptor antagonist binds to the human GAL3 receptor with a binding affinity at least ten-Fold higher than the binding affinity with which it binds to the human GAL1 receptor;
  • the GAL3Receptor antagonist binds to the human GAL3 receptor with a binding affinity at least ten-Fold higher than the binding affinity with which it binds to each of the following transporters: serotonin transporter, norepinephrine transporter, and dopamine transporter.
  • FIG. 1 Rat Forced Swim Test Results (Immobility: Normal Rats)
  • FIG. 2 Rat Forced Swim Test Results (Climbing: Normal Rats)
  • Example 92 A significant increase in climbing was observed for rats injected with Example 92 at 10 mg/kg, relative to vehicle injected controls (p ⁇ 0.01, ANOVA and Student-Nerman-Keuls), but not in rats dosed with Example 92 at 30 mg/kg ip.
  • FIG. 3 Rat Forced Swim Test Results (Swimming: Normal Rats)
  • FIG. 4 Social Interaction Test Results (Social Interaction: Unfamiliar Rats)
  • Example 92 When the dose of Example 92 was increased to 100 mg/kg, the amount of social interaction time was significantly less than measured after chlordiazepoxide at 5 mg/kg ip or Example 92 at 30 mg/kg ip (p ⁇ 0.01). Significance in all cases was determined by ANOVA and Student-Nerman-Keuls.
  • FIG. 5 Western Blot Results
  • the anti-GAL3 antiserum labeled proteins in membranes only from rat GAL3-transfected cells (Lane 2); a predominant band was evident with an apparent molecular weight of approximately 56 kDa, (somewhat higher than the amino acid-derived value of 40.4 kDa).
  • the apparently high molecular weight observed for rat GAL3 very likely reflects post-translational processing such as glycosylation; note that rat GAL3 contains multiple N-terminal glycosylation sites (Smith et al., 1998).
  • Relative to the predominant band additional species of higher molecular weight as well as lower molecular weight were labeled by the GAL3 antiserum. These are interpreted as protein aggregates of C-terminal fragments, as they are absent in mock-transfected cells.
  • the present invention provides a method of treating a subject suffering from depression which comprises administering to the subject an amount of compound effective to treat the subject's depression wherein the compound has the structure:
  • W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
  • R 11 is H, straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , aryl, or aryl (C 1 -C 6 )alkyl;
  • R 12 is straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 or —(CH 2 ) m —Z;
  • R 13 is a bicyclic alkyl ring system, adamantyl, noradamantyl, C 3 -C 10 cycloalkyl, heteroaryl, aryl, aryl(C 1 -C 6 ) alkyl, Q 1 or Q 2 ;
  • aryl may be substituted with one or more C 1 -C 10 straight chained or branched alkyl, aryl, heteroaryl, or N(R 19 )—z;
  • each J is independently O, S, C(R 22 ) 2 or NR 4 ;
  • R 4 is H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl or aryl;
  • R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • R 15 is straight chained or branched C 3 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, (C(R 19 ) 2 ) m N(R 16 ) 2 or (C(R 19 ) 2 ) m —Z ;
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • R 18 is straight chained or branched C 1 -C 6 alkyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl
  • each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl, or aryl(C 1 -C 6 ) alkyl;
  • each R 22 is independently H, F, Cl or C 1 -C 4 straight chained or branched alkyl
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
  • Z is C 3 -C 10 cycloalkyl, C 4 -C 7 cyclic ether, C 4 -C 7 cyclic thioether, aryl, or heteroaryl; or
  • the invention provides a method of treating a subject suffering from depression which comprises administering to the subject an amount of compound effective to treat the subject's depression wherein the compound has the structure:
  • W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
  • R 11 is H, straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , aryl or aryl(C 1 -C 6 ) alkyl;
  • R 12 is straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , or —(CH 2 ) m —Z;
  • R 13 is a bicyclic alkyl ring system, aryl or aryl (C 1 -C 6 )alkyl;
  • R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • R 15 is straight chained or branched C 3 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
  • Z is C 3 -C 10 cycloalkyl, aryl, or heteroaryl
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • R 18 is straight chained or branched C 1 -C 6 alkyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl
  • each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • the invention provides a method of treating a subject suffering from depression which comprises administering to the subject an amount of compound effective to treat the subject's depression wherein the compound has the structure:
  • W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
  • R 13 is an aryl, adamantyl, noradamantyl, C 3 -C 10 cycloalkyl, heteroaryl, Q 1 or Q 2 ;
  • aryl may be substituted with one or more C 1 -C 10 straight chained or branched alkyl, aryl, heteroaryl, or N(R 19 )—Z;
  • each J is independently O, S, C(R 22 ) 2 or NR 4 ;
  • R 4 is —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl or aryl;
  • R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • R 15 is straight chained or branched C 3 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
  • Z is C 3 -C 10 cycloalkyl, aryl, or heteroaryl
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • R 18 is straight chained or branched C 1 -C 6 alkyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl
  • each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
  • each R 22 is independently H, F, Cl or C 1 -C 4 straight chained or branched alkyl
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • the invention provides a method of treating a subject suffering from depression which comprises administering to the subject an amount of compound effective to treat the subject's depression wherein the compound has the structure:
  • W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
  • R 13 is a bicyclic alkyl ring system, aryl or aryl (C 1 -C 6 )alkyl;
  • R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • R 15 is (C(R 19 ) 2 ) m —N(R 16 ) 2 ;
  • Z is C 3 -C 10 cycloalkyl, aryl, or heteroaryl
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • bicyclic alkyl ring systems includes, but is not limited to, bicyclo[2.2.1]heptane, bicyclo[3.1.1]heptane and bicyclo[2.2.2]octane.
  • the bicyclic alkyl ring systems may be substituted with one or more of the following: —F, —NO 2 , —CN, straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, —N(R 21 ) 2 , —OR 21 , —COR 21 , —CO 21 R 21 , —CON(R 21 ) 2 or (CH 2 ) n —O—(CH 2 ) m —CH 3 .
  • cycloalkyl includes, C 3 -C 7 cycloalkyl moieties which may be substituted with one or more of the following: —F, —NO 2 , —CN, straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 3 -C 7 cycloalkyl, C 3 -C 7 monofluorocycloalkyl, C 3 -C 7 polyfluorocycloalkyl, C 5 -C 7 cycloalkenyl, —N(R 4 ) 2 , —OR 4 , —COR 4 , —NCOR 4 ,
  • cyclohexyl includes, cyclohexyl groups which may be substituted with one or more of the following: —F, —NO 2 , —CN, straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 3 -C 7 cycloalkyl, C 3 -C 7 monofluorocycloalkyl, C 3 -C 7 polyfluorocycloalkyl, C 5 -C 7 cycloalkenyl, —N(R 4 ) 2 , —OR 4 , —COR 4 , —NCOR 4 , —CO 2 R 4
  • cycloalkyl includes, C 5 -C 7 cycloalkenyl moieties which may be substituted with one or more of the following: —F, —Cl, —Br, —I, —NO 2 , —CN, straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 3 -C 7 cycloalkyl, C 3 -C 7 monofluorocycloalkyl, C 3 -C 7 polyfluorocycloalkyl, C 5 -C 7 cycloalkenyl, —N(R 4 ) 2 , —OR 4
  • heteroaryl is used to include five and six membered unsaturated rings that may contain one or more oxygen, sulfur, or nitrogen atoms.
  • heteroaryl groups include, but are not limited to, furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, and triazinyl.
  • heteroaryl is used to include fused bicyclic ring systems that may contain one or more heteroatoms such as oxygen, sulfur and nitrogen.
  • heteroaryl groups include, but are not limited to, indolizinyl, indolyl, isoindolyl, benzo[b]furanyl, benzo[b]thiophenyl, indazolyl, benzimidazolyl, purinyl, benzoxazolyl, benzisoxazolyl, benzo[b]thiazolyl, imidazo[2,1-b]thiazolyl, cinnolinyl, quinazolinyl, quinoxalinyl, 1,8-Naphthyridinyl, pteridinyl, quinolinyl, isoquinolinyl, phthalimidyl and 2,1,3-benzothiazolyl.
  • heteroaryl also includes those chemical moieties recited above which may be substituted with one or more of the following: —F, —Cl, —Br, —I, —NO 2 , —CN, straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 3 -C 7 cycloalkyl, C 3 -C 7 monofluorocycloalkyl, C 3 -C 7 polyfluorocycloalkyl, C 5 -C 7 cycloalkenyl, —N(R 4 ) 2 , —OR 4 , —COR 4 , —NCOR 4
  • heteroaryl further includes the N-oxides of those chemical moieties recited above which include at least one nitrogen atom.
  • aryl is phenyl or naphthyl.
  • the term “aryl” also includes phenyl and naphthyl which may be substituted with one or more of the following: —F, —Cl, —Br, —I, —NO 2 , —CN, straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 3 -C 7 cycloalkyl, C 3 -C 7 monofluorocycloalkyl, C 3 -C 7 polyfluorocycloalkyl, C 5 -C 7 cycloalkenyl, —N(R 4 ) 2
  • the compound is enantiomerically and diasteriomerically pure. In one embodiment, the compound is enantiomerically or diasteriomerically pure.
  • the compound in one embodiment of any of the methods described herein, can be administered orally.
  • X is:
  • X is NR 11 R 12 and R 11 is H or straight chained or branched C 1 -C 7 alkyl.
  • the compound has the structure:
  • R 13 is a bicyclic alkyl ring system, cyclohexyl or aryl.
  • R 14 is H, straight chained or branched C 1 -C 6 alkyl or (CH 2 ) q —O—(CH 2 ) m —CH 3 .
  • R 14 is H, straight chained or branched C 1 -C 6 alkyl or (CH 2 ) q —O—(CH 2 ) m —CH 3 .
  • the compound is selected from the group consisting of:
  • Y is
  • U is NR 16 .
  • R 16 is (CH 2 ) m —Z.
  • Z is aryl or heteroaryl.
  • the compound is selected from the group consisting of:
  • the compound is selected from the group consisting of:
  • Y is
  • U is NR 16 .
  • the compound is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl
  • the compound is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl
  • the compound is selected from the group consisting of:
  • the compound is selected from the group consisting of:
  • X is N(CH 3 ) 2 .
  • Y is
  • R 13 is an aryl substituted with a C 1 -C 10 straight chained alkyl.
  • the compound is selected from a group consisting of:
  • the invention provides a method of treating a subject suffering from anxiety which comprises administering to the subject an amount of compound effective to treat the subject's anxiety wherein the compound has the structure:
  • W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
  • R 11 is H, straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m CH 3 , aryl, or aryl (C 1 -C 6 )alkyl;
  • R 12 is straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , or —(CH 2 ) m —Z;
  • R 13 is a bicyclic alkyl ring system, adamantyl, noradamantyl, C 3 -C 10 cycloalkyl, heteroaryl, aryl, aryl(C 1 -C 6 )alkyl, Q 1 or Q 2 ;
  • aryl may be substituted with one or more C 1 -C 10 straight chained or branched alkyl, aryl, heteroaryl, or N(R 19 )—Z;
  • each J is independently O, S, C(R 22 ) 2 or NR 4 ;
  • R 4 is H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl or aryl;
  • R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • R 15 is straight chained or branched C 3 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, (C(R 19 ) 2 ) m N(R 16 ) 2 or (C(R 19 ) 2 ) m —Z;
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • R 18 is straight chained or branched C 1 -C 6 alkyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl
  • each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl, or aryl(C 1 -C 6 )alkyl;
  • each R 22 is independently H, F, Cl or C 1 -C 4 straight chained or branched alkyl
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
  • Z is C 3 -C 10 cycloalkyl, C 4 -C 7 cyclic ether, C 4 -C 7 cyclic thioether, aryl, or heteroaryl; or
  • the invention provides a method of treating a subject suffering from anxiety which comprises administering to the subject an amount of compound effective to treat the subject's anxiety wherein the compound has the structure:
  • W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
  • R 11 is H, straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , aryl or aryl(C 1 -C 6 )alkyl;
  • R 12 is straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , or —(CH 2 ) m —Z;
  • R 13 is a bicyclic alkyl ring system, aryl or aryl (C 1 -C 6 ) alkyl;
  • R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • R 15 is straight chained or branched C 3 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
  • Z is C 3 -C 10 cycloalkyl, aryl, or heteroaryl
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • R 18 is straight chained or branched C 1 -C 6 alkyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl
  • each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • the invention provides a method of treating a subject suffering from anxiety which comprises administering to the subject an amount of compound effective to treat the subject's anxiety wherein the compound has the structure:
  • W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
  • R 13 is an aryl, adamantyl, noradamantyl, C 3 -C 10 cycloalkyl, heteroaryl, Q 1 or Q 2 ;
  • aryl may be substituted with one or more C 1 -C 10 straight chained or branched alkyl, aryl, heteroaryl, or N(R 19 )—Z;
  • each J is independently O, S, C(R 22 ) 2 or NR 4 ;
  • R 4 is —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl or aryl;
  • R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • R 15 is straight chained or branched C 3 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
  • Z is C 3 -C 10 cycloalkyl, aryl, or heteroaryl
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • R 18 is straight chained or branched C 1 -C 6 alkyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl
  • each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
  • each R 22 is independently H, F, Cl or C 1 -C 4 straight chained or branched alkyl
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • the invention provides a method of treating a subject suffering from anxiety which comprises administering to the subject an amount of compound effective to treat the subject's anxiety wherein the compound has the structure:
  • W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
  • R 13 is a bicyclic alkyl ring system, aryl or aryl (C 1 -C 6 ) alkyl;
  • R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • R 15 is (C(R 19 ) 2 ) m —N(R 16 ) 2 ;
  • Z is C 3 -C 10 cycloalkyl, aryl, or heteroaryl
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • bicyclic alkyl ring systems includes, but is not limited to, bicyclo[2.2.1]heptane, bicyclo[3.1.1]heptane and bicyclo[2.2.2]octane.
  • the bicyclic alkyl ring systems may be substituted with one or more of the following: —F, —NO 2 , —CN, straight chained or branched C 1 -C 7 alkyl, straight chained.
  • cycloalkyl includes, C 3 -C 7 cycloalkyl moieties which may be substituted with one or more of the following: —F, —NO 2 , —CN, straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 3 -C 7 cycloalkyl, C 3 -C 7 monofluorocycloalkyl, C 3 -C 7 polyfluorocycloalkyl, C 5 -C 7 cycloalkenyl, —N(R 4 ) 2 , —OR 4 , —COR 4 , —NCOR 4 ,
  • cyclohexyl includes, cyclohexyl groups which may be substituted with one or more of the following: —F, —NO 2 , —CN, straight chained or branched C 1 -C 7 alkyl, straight chained.
  • C 1 -C 7 monofluoroalkyl straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 3 -C 7 cycloalkyl, C 3 -C 7 monofluorocycloalkyl, C 3 -C 7 polyfluorocycloalkyl, C 5 -C 7 cycloalkenyl, —N(R 4 ) 2 , —OR 4 , —COR 4 , —NCOR 4 , —CO 2 R 4 , —CON(R 4 ) 2 or (CH 2 ) n —O—(CH 2 ) m —CH 3 .
  • cycloalkenyl includes, C 5 -C 7 cycloalkenyl moieties which may be substituted with one or more of the following: —F, —Cl, —Br, —I, —NO 2 , —CN, straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 3 -C 7 cycloalkyl, C 3 -C 7 monofluorocycloalkyl, C 3 -C 7 polyfluorocycloalkyl, C 5 -C 7 cycloalkenyl, —N(R 4 ) 2 , —OR 4
  • heteroaryl is used to include five and six membered unsaturated rings that may contain one or more oxygen, sulfur, or nitrogen atoms.
  • heteroaryl groups include, but are not limited to, furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, and triazinyl.
  • heteroaryl is used to include fused bicyclic ring systems that may contain one or more heteroatoms such as oxygen, sulfur and nitrogen.
  • heteroaryl groups include, but are not limited to, indolizinyl, indolyl, isoindolyl, benzo[b]furanyl, benzo[b]thiophenyl, indazolyl, benzimidazolyl, purinyl, benzoxazolyl, benzisoxazolyl, benzo[b]thiazolyl, imidazo[2,1-b]thiazolyl, cinnolinyl, quinazolinyl, quinoxalinyl, 1,8-Naphthyridinyl, pteridinyl, quinolinyl, isoquinolinyl, phthalimidyl and 2,1,3-benzothiazolyl.
  • heteroaryl also includes those chemical moieties recited above which may be substituted with one or more of the following: —F, —Cl, —Br, —I, —NO 2 , —CN, straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 3 -C 7 cycloalkyl, C 3 -C 7 monofluorocycloalkyl, C 3 -C 7 polyfluorocycloalkyl, C 5 -C 7 cycloalkenyl, —N(R 4 ) 2 , —OR 4 , —COR 4 , —NCOR 4 , —CO
  • heteroaryl further includes the N-oxides of those chemical moieties recited above which include at least one nitrogen atom.
  • aryl is phenyl or naphthyl.
  • the term “aryl” also includes phenyl and naphthyl which may be substituted with one or more of the following: —F, —Cl, —Br, —I, —NO 2 , —CN, straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 3 -C 7 cycloalkyl, C 3 -C 7 monofluorocycloalkyl, C 3 -C 7 polyfluorocycloalkyl, C 5 -C 7 cycloalkenyl, —N(R 4 ) 2
  • the compound is enantiomerically and diasteriomerically pure. In one embodiment, the compound is enantiomerically or diasteriomerically pure.
  • the compound can be administered orally.
  • X is:
  • X is NR 11 R 12 and R 11 is H or straight chained or branched C 1 -C 7 alkyl.
  • the compound has the structure:
  • R 13 is a bicyclic alkyl ring system, cyclohexyl or aryl.
  • R 14 is H, straight chained or branched C 1 -C 6 alkyl or (CH 2 ) q —O—(CH 2 ) m —CH 3 .
  • the compound is selected from the group consisting of:
  • Y is
  • U is NR 16 .
  • R 16 is (CH 2 ) m —Z.
  • Z is aryl or heteroaryl.
  • the compound is selected from the group consisting of:
  • the compound is selected from the group consisting of:
  • Y is
  • U is NR 16 .
  • the compound is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl
  • the compound is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl
  • the compound is selected from the group consisting of:
  • the compound is selected from the group consisting of:
  • X is N(CH 3 ) 2 .
  • Y is
  • R 13 is an aryl substituted with a C 1 -C 10 straight chained alkyl.
  • the compound is selected from a group consisting of:
  • the invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound having the structure:
  • W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
  • R 11 is H, straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , aryl, or aryl (C 1 -C 6 )alkyl;
  • R 12 is straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , or —(CH 2 ) m —Z;
  • R 13 is a bicyclic alkyl ring system, adamantyl, noradamantyl, C 3 -C 10 cycloalkyl, heteroaryl, aryl, aryl(C 1 -C 6 )alkyl, Q 1 or Q 2 ;
  • aryl may be substituted with one or more C 1 -C 10 straight chained or branched alkyl, aryl, heteroaryl, or N(R 19 )—Z;
  • each J is independently O, S, C(R 22 ) 2 or NR 4 ;
  • R 4 is H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl or aryl;
  • R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • R 15 is straight chained or branched C 3 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, (C(R 19 ) 2 ) m N(R 16 ) 2 or (C(R 19 ) 2 ) m —Z;
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, (CH 2 ) m ⁇ Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • R 18 is straight chained or branched C 1 -C 6 alkyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl
  • each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl, or aryl(C 3 -C 6 )alkyl;
  • each R 22 is independently H, F, Cl or C 1 -C 4 straight chained or branched alkyl
  • each m is an integer from 0 to 4 inclusive;
  • n is an integer from 1 to 4 inclusive
  • U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
  • Z is C 3 -C 10 cycloalkyl, C 4 -C 7 cyclic ether, C 4 -C 7 cyclic thioether, aryl, or heteroaryl; or
  • the invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound having the structure:
  • W is H, —F, —Cl, —Br, —I, CN, methyl, ethyl, propyl, methoxy or ethoxy;
  • R 11 is H, straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , aryl or aryl(C 1 -C 6 )alkyl;
  • R 12 is straight chained or branched C 1 -C 7 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , or —(CH 2 ) m —Z;
  • R 13 is a bicyclic alkyl ring system, aryl or aryl (C 1 -C 6 ) alkyl;
  • R 14 is H, straight chained or branched C 1 -C 6 alkyl, (CH 2 ) q —O—(CH 2 ) m —CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z ;
  • R 15 is straight chained or branched C 3 -C 6 alkyl, (CH 2 ) q —O—(CH 2 )_—CH 3 , C 3 -C 6 cycloalkyl, or (C(R 19 ) 2 ) m —Z;
  • U is O, —NR 16 , S, C(R 17 ) 2 , or —NSO 2 R 16 ;
  • Z is C 3 -C 10 cycloalkyl, aryl, or heteroaryl
  • R 16 is straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 17 is independently H; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 , —COOR 21 , straight chained or branched C 1 -C 7 alkyl, straight chained or branched C 1 -C 7 monofluoroalkyl, straight chained or branched C 1 -C 7 polyfluoroalkyl, straight chained or branched C 2 -C 7 alkenyl, straight chained or branched C 2 -C 7 alkynyl, C 5 -C 7 cycloalkenyl, —(CH 2 ) m —Z, or (CH 2 ) n —O—(CH 2 ) m —CH 3 ;
  • R 18 is straight chained or branched C 1 -C 6 alkyl, —(CH 2 ) m —Z, or (CH 2 ) q —O—(CH 2 ) m —CH 3 ;
  • each R 19 is independently H, or straight chained or branched C 1 -C 6 alkyl
  • each R 20 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl or C 5 -C 7 cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 21 , —OCOR 21 , —COR 21 , —NCOR 21 , —N(R 21 ) 2 , —CON(R 21 ) 2 or —COOR 21 ; aryl or heteroaryl; or two R 20 groups present on adjacent carbon atoms can join together to form a methylenedioxy group;
  • each R 21 is independently —H; straight chained or branched C 1 -C 7 alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7 alkenyl or alkynyl; C 3 -C 7 cycloalkyl, C 5 -C 7 cycloalkenyl, aryl or aryl(C 1 -C 6 )alkyl;
  • each m is an integer from 0 to 4 inclusive;
US10/723,961 2001-01-31 2003-11-26 Use of GAL3 antagonist for treatment of depression Abandoned US20040127502A1 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
US10/723,961 US20040127502A1 (en) 2001-01-31 2003-11-26 Use of GAL3 antagonist for treatment of depression
US11/517,589 US7465750B2 (en) 2001-01-31 2006-09-06 Use of GAL3 antagonist for treatment of depression and/or anxiety and compounds useful in such methods
US12/314,675 US20090318504A1 (en) 2001-01-31 2008-12-15 Use of GAL3 receptor antagonists for the treatment of depression and/or anxiety and compounds useful in such methods

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