PYRAZINONES AND TRIAZINONES AND THEIR DERIVATIVES THEREOF

Abstract: Corticotropin releasing factor (CRF) antagonists of Formula (I), and their use in treating psychiatric disorders and neurological diseases including major depression, anxiety-related disorders, post-traumatic stress disorders, supranuclear palsy and eating disorders.

Description: TITLE PYRAZINONES AND TRIAZINONES AND THEIR DERIVATIVES THEREOF FIELD OF THE INVENTION This invention relates to novel compounds and pharmaceutical compositions, and to methods of using same in the treatment of psychiatric disorders and neurological diseases including major depression, anxiety-related disorders, post-traumatic stress disorders, supranuclear palsy and eating disorders . BACKGROUND OF THE INVENTION Corticotropin releasing factor (herein referred to as CRF) , a 41 amino acid peptide, is the primary physiological regulator of proopiomelanocortin (PO C) -derived peptide secretion from the anterior pituitary gland [J. Rivier et al., Proc . Nat . Acad. Sci . (USA) 80:4851 (1983); W. Vale et al., Science 213:1394 (1981)]. In addition to its endocrine role at the pituitary gland, immunohistochemical localization of CRF has demonstrated that the hormone has a broad extrahypothalamic distribution in the central nervous system and produces a wide spectrum of autonomic, electrophysiological and behavioral effects consistent with a neurotransmitter or neuromodulator role in brain [W. Vale et al . , Rec . Prog. Hor . Res . 39:245 (1983); G.F. Koob, Persp. Behav. Med. 2:39 (1985); E.B. De Souza et al . , J " . Neurosci . 5:3189 (1985)]. There is also evidence that CRF plays a significant role in integrating the response of the immune system to physiological, psychological, and immunological stressors [J.E. Blalock, Physiological Reviews 69:1 (1989); J.E. Morley, Life Sci . 41:527 (1987)]. Clinical data provide evidence that CRF has a role in psychiatric disorders and neurological diseases including depression, anxiety-related disorders and eating disorders. A role for CRF has also been postulated in the etiology and pathophysiology of Alzheimer's disease, Parkinson's disease, Huntington's disease, progressive supranuclear palsy and amyotrophic lateral sclerosis as they relate to the dysfunction of CRF neurons in the central nervous system [for review see E.B. De Souza, Hosp. Practice 23:59 (1988) ] . In affective disorder, or major depression, the concentration of CRF is significantly increased in the cerebral spinal fluid (CSF) of drug-free individuals [C.B. Nemeroff et al . , Science 226:1342 (1984); CM. Banki et al., Am. J " . Psychiatry 144:873 (1987); R.D. France et al . , Biol . Psychiatry 28:86 (1988); M. Arato et al . , Biol Psychiatry 25:355 (1989)]. Furthermore, the density of CRF receptors is significantly decreased in the frontal cortex of suicide victims, consistent with a hypersecretion of CRF [C.B. Nemeroff et al . , Arch . Gen . Psychiatry 45:577 (1988) ] . In addition, there is a blunted adrenocorticotropin (ACTH) response to CRF (i.v. administered) observed in depressed patients [P.W. Gold et al., Am J. Psychiatry 141:619 (1984); F. Holsboer et al . , Psychoneuroendocrinology 9:147 (1984); P.W. Gold et al . , New Eng. J. Med. 314:1129 (1986)]. Preclinical studies in rats and non-human primates provide additional support for the hypothesis that hypersecretion of CRF may be involved in the symptoms seen in human depression [R.M. Sapolsky, Arch . Gen . Psychiatry 46:1047 (1989)]. There is preliminary evidence that tricyclic antidepressants can alter CRF levels and thus modulate the numbers of CRF receptors in brain [Grigoriadis et al . , Neuropsychopharmacology 2:53 (1989)]. There has also been a role postulated for CRF in the etiology of anxiety-related disorders. CRF produces anxiogenic effects in animals and interactions between benzodiazepine / non-benzodiazepine anxiolytics and CRF have been demonstrated in a variety of behavioral anxiety models [D.R. Britton et al . , Life Sci . 31:363 (1982); C.W. Berridge and A.J. Dunn Regul . Peptides 16:83 (1986)]. Preliminary studies using the putative CRF receptor antagonist a-helical ovine CRF (9-41) in a variety of behavioral paradigms demonstrate that the antagonist produces "anxiolytic-like" effects that are qualitatively similar to the benzodiazepines [C.W. Berridge and A.J. Dunn Hor . Behav. 21:393 (1987), Brain Research Reviews 15:71 (1990)]. Neurochemical, endocrine and receptor binding studies have all demonstrated interactions between CRF and benzodiazepine anxiolytics providing further evidence for the involvement of CRF in these disorders. Chlordiazepoxide attenuates the "anxiogenic" effects of CRF in both the conflict test [K.T. Britton et al . , Psychophar acology 86:170 (1985); K.T. Britton et al . , Pεychopharmacology 94:306 (1988)] and in the acoustic startle test [N.R. Swerdlow et al . , Psychopharmacology 88:147 (1986)] in rats. The benzodiazepine receptor antagonist (Rol5-1788) , which was without behavioral activity alone in the operant conflict test, reversed the effects of CRF in a dose-dependent manner while the benzodiazepine inverse agonist (FG7142) enhanced the actions of CRF [K.T. Britton et al . , Psychopharmacology 94:306 (1988)]. The mechanisms and sites of action through which the standard anxiolytics and antidepressants produce their therapeutic effects remain to be elucidated. It has been hypothesized however, that they are involved in the suppression of the CRF hypersecretion that is observed in these disorders. Of particular interest is that preliminary studies examining the effects of a CRF receptor antagonist (a-helical CRF9-41) in a variety of behavioral paradigms have demonstrated that the CRF antagonist produces "anxiolytic-like" effects qualitatively similar to the benzodiazepines [for review see G.F. Koob and K.T. Britton, In: Corticotropin-Releasing Factor: Basic and Clinical Studies of a Neuropeptide, E.B. De Souza and C.B. Nemeroff eds., CRC Press p221 (1990)]. DuPont Merck PCT application WO95/10506 describes corticotropin releasing factor antagonist compounds and their use to treat psychiatric disorders and neurological diseases . European patent application 0 576 350 Al by Elf Sanofi describes corticotropin releasing factor antagonist compounds useful in the treatment of CNS and stress disorders . Pfizer patent applications WO 94/13676, WO 94/13677, WO 94/13661, WO 95/33750, WO 95/34563, WO 95/33727 describe corticotropin releasing factor antagonist compounds useful in the treatment of CNS and stress disorders. All of the aforementioned references are hereby incorporated by reference . The compounds and the methods of the present invention provide for the production of compounds capable of inhibiting the action of CRF at its receptor protein in the brain. These compounds would be useful in the treatment of a variety of neurodegenerative, neuropsychiatric and stress-related disorders such as affective disorders, anxiety, depression, post-traumatic stress disorders, supranuclear palsy, seizure disorders, stroke, irritable bowel syndrome, immune suppression, Alzheimer's disease, gastrointestinal disease, anorexia nervosa or other eating disorders, drug or alcohol withdrawal symptoms, drug addiction, inflammatory disorders and fertility problems. It is further asserted that this invention may provide compounds and pharmaceutical compositions suitable for use in such a method. SUMMARY OF THE INVENTION This invention is a class of novel compounds which are CRF receptor antagonists and which can be represented by Formula (I) : (i) or a pharmaceutically acceptable salt form thereof, wherein Z is CR 2 or N; when Z is CR 2 : Y is NR 4 , 0 or S(0) n ; Ar is phenyl, naphthyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, 1, 3 , 5-triazinyl, 1, 2 , 4-triazinyl , furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, indolinyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl , 2 , 3-dihydrobenzofuranyl, 2 , 3-dihydrobenzothienyl, benzothiazolyl , indazolyl, isoxazolyl or pyrazolyl, each substituted with 0 to 4 R5 groups; wherein Ar is attached to Y through an unsaturated carbon; R 1 is H, halo, Ci-Cio alkyl, C2-C10 alkenyl, C2- C10 alkynyl, C3-C8 cycloalkyl, C1-C4 haloalkyl, aryl, heterocyclyl , -CN, -OR 7 , -SH, -S(0) n R 13 . -COR 7 , -CONR 6 R 7 , -Cθ2R 7 , -OC(0)R 13 , -NR 8 COR 7 , -N(COR 7 ) 2/ -NR 8 CONR 6 R 7 , -NR 8 C02R 7 , or -NR 6 R 7 , wherein C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl or C3-C8 cycloalkyl is each substituted with 0 to 3 substituents independently selected at each occurrence from Ci-Cβ alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, -CN, -OR 7 , -SH, -S (0) n R 13 , -COR 7 , -C02R 7 , -0C(0)R 13 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , -NR 8 C02R 7 , -NR 6 R 7 , -CONR 6 R 7 , aryl and heterocyclyl; R 2 is H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, 3 -C 6 cycloalkyl, halo, -CN, C1 . -C4 haloalkyl, -NR 9 R 10 , -NR 9 COR 10 , -NR 9 Cθ2R 10 , -OR 11 , -SH or -S(0) n R 12 ; R 3 is Ci-Cio alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C8 cycloalkyl, C1-C4 haloalkyl, aryl, heterocyclyl, -CN, -OR 7 , -S(0)2P- 13 - -COR 7 , -CO2R 7 , -NR 8 COR 7 , -N(COR 7 ) 2 . -NR 8 CONR 6 R 7 , -CONR 6 R 7 , -NR 8 Cθ2R 7 , or -NR 6 R 7 , wherein C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl or C3-C8 cycloalkyl is each substituted with 0 to 3 subεtituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, -CN, -OR 7 , -S(0) n R 13 . -COR 7 , -CO2R 7 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , -NR 8 C02R 7 , -NR 6 R 7 , -CONRSR 7 , aryl and heterocyclyl, with the proviso that when R-* * is aryl, Ar is not imidazolyl; R 4 is H, C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl, wherein C2-C6 alkenyl or C2-C6 alkynyl is optionally substituted with C1-C4 alkyl or C3-C6 cycloalkyl and wherein C1-C6 alkyl is optionally substituted with C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, -OR 7 , -S(0) n R 12 , -CO2R 7 , -NR 6 R 7 or -NR 9 COR 10 ; R5 is independently selected at each occurrence from Cl-Cio alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C6 cycloalkyl, C4-C12 cycloalkylalkyl, aryl, heterocyclyl, -NO2 halo, -CN, C1-C4 haloalkyl, -NR 6 R 7 , -NR 8 COR 7 , -NR 8 C0 2 R 7 , -OR 7 , -COR 7 , -CO2R 7 , -CONR 6 R 7 , -CON(OR 9 )R 7 , -SH, and -S(0) n R 13 - wherein C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C6 cycloalkyl and C4-C12 cycloalkylalkyl are substituted with 0 to 3 substituents independently selected at each occurrence from C1 . -C4 alkyl, -NO2 , halo, -CN, -OR 7 , -COR 7 , -CO2R 7 , -CONR 6 R 7 , -NR 6 R 7 , -NR 8 COR 7 , -NR 8 C0 2 R 7 and -S(0) n R 13 ; R-5 and R 7 are independently selected at each occurrence from H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, C4- C12 cycloalkylalkyl, aryl, aryl(Cι~C4 alkyl)-, heterocyclyl, heterocyclyl (C1-C4 alkyl)-, morpholinoethyl, mopholinopropyl and morpholinobutyl; or -NR^R 7 taken together as a whole is piperidine, pyrrolidine, piperazine, N-methyl- piperazine, morpholine or thiomorpholine; wherein C1-C4 alkyl, may be substituted with 0 to 2 substituents independently selected at each occurrence from -OH or C1-C4 alkoxy groups; R 8 is independently at each occurrence H or C1-C4 alkyl; R 9 and R *-- are independently at each occurrence selected from H, C1-C4 alkyl and C3-C6 cycloalkyl; R 11 is H, C1-C4 alkyl, C1-C4 haloalkyl, or C3-C6 cycloalkyl; R 12 is C1-C4 alkyl, C1-C4 haloalkyl or -NR 6 R 7 ; R 13 is C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, C4-C12 cycloalkylalkyl, -NR 6 R 7 , aryl, aryl(Cι-C4 alkyl)-, heterocyclyl or heterocyclyl (C1-C4 alkyl) -; R 14 is C1-C4 alkyl, C1 . -C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, C4-C12 cycloalkylalkyl, -NR 15 R 16 ; R 15 and R ( - * are independently selected at each occurrence from H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl and C4- C12 cycloalkylalkyl; or -NR 1 R---6 taken together as a whole is piperidine, pyrrolidine, piperazine, N-methyl-piperazine, morpholine or thiomorpholine; aryl is phenyl, biphenyl or naphthyl, each substituted with 0 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, -CN, -OR 15 , -SH, -S(0) n R 14 , -COR 15 , -C02R 15 , -0C(0)R 14 , -NO2, -NR 8 C0R 15 , -N(COR 15 ) 2 , -NR 8 CONR 15 R 16 , -NR 8 C02R 15 , -NR 15 R 16 and -CONR 15 R 16 ; heterocyclyl is 5- to 10- membered heterocyclic ring which may be saturated, partially unsaturated or aromatic, and which consists of carbon atoms and from 1 to 4 heteroatoms independently selected from the group consisting of N, 0 and S, wherein the heterocyclic ring is substituted with 0 to 3 substituents independently selected at each occurrence from Cι~ Cβ alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, -CN, -OR 15 , -SH, -S(0) n R 14 - -COR 15 , -C02R 15 , -OC(0)R 14 , -NR 8 COR 15 , -N(COR 15 ) 2 , -NR 8 CONR 15 R 16 , -NR 8 C02R 15 , -NR 15 R 16 , and -CONR 15 R 16 ; and n is independently at each occurrence 0, 1 or 2 ; and wherein, when Z is N: Y is NR 4 , 0 or S(0) n ; Ar, R 1 , R 4 , R 5 , R6, R 7 , R 8 , R , R 10, R11, R 12 , R 13 , R 14, R 15 , R 1( 5, aryl, heterocyclyl, heterocyclyl and n are as defined above, but R 3 is C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C8 cycloalkyl, C1-C4 haloalkyl, aryl, heterocyclyl, -CN, -S(0)2R 13 , -CO2R 7 , -COR 7 or -CONR 6 R 7 , wherein C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl or C3-C8 cycloalkyl is each substituted with 0 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, -CN, -OR 7 , -S(0) n R 13 , -COR 7 , -CO2R 7 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , -NR 8 C02R 7 , -NR 6 R 7 , -CONR 6 R 7 , aryl and heterocyclyl, with the proviso that when R 3 is aryl, Ar is not imidazolyl . [3] Preferred compounds of this invention are compounds of Formula (I) and pharmaceutically acceptable salts and pro-drug forms thereof, wherein: Z is CR 2 ; Y is NR 4 or O; Ar is phenyl or pyridyl, each substituted with 0 to 4 R 5 groups ; R 1 is H, halo, C1 . -C 4 alkyl, cyclopropyl, C1-C4 haloalkyl, -CN, -NR 6 R 7 , -CONR 6 R 7 , -OR 7 , -COR 7 , -C0 2 R 7 or -S(0) n R 13 , wherein C1-C4 alkyl is substituted with 0 to 3 substituents independently selected at each . occurrence from C1-C4 alkyl, C3-C6 cycloalkyl, halo, -CN, -OR 7 , -S(0)nR 13 . -COR 7 , -CO2R 7 , -NR 8 COR 7 , -NR 8 C02R 7 , -NR 6 R 7 and aryl; R 2 is H, C 1 -C 4 alkyl, halo, C 1 -C 4 haloalkyl; R 3 is C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C8 cycloalkyl, C1-C4 haloalkyl, aryl, heterocyclyl, -CN, -OR 7 , -S(0)2R 13 , -COR 7 , -CO2R 7 , -NR 8 COR 7 , -N(C0R 7 ) 2 , -NR 8 CONR 6 R 7 , -CONR 6 R 7 , -NR 8 C02R 7 , or -NR 6 R 7 , wherein C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl or C3-C8 cycloalkyl is each substituted with 0 to 3 substituents independently selected at each occurrence from Ci-Cβ alkyl, C 3 -C 6 cycloalkyl, C 1 -C 4 haloalkyl, halo, -CN, -OR 7 , -S(0) n R 13 , -C0 2 R 7 , -NR 8 COR 7 , -NR 8 CONR 6 R 7 , -NR 8 C0 2 R 7 , -NR 6 R 7 , aryl and heterocyclyl ; R 4 is H, C1-C6 alkyl or C2-C6 alkenyl, wherein C1-C6 alkyl is optionally substituted with C1-C4 alkyl, C1-C4 haloalkyl, -OR 7 , -S(0) n R 12 . -CO2R 7 , -NR β R 7 or -NR 9 COR 10 ; R 5 is independently selected at each occurrence from Ci-Ce alkyl, C -Ce alkenyl, C 2 -Ce alkynyl, C 3 -C 6 cycloalkyl, C4-C8 cycloalkylalkyl, aryl, heterocyclyl, C 1 -C 4 haloalkyl, halo, -CN, -N0 2 , -NR 6 R 7 , -COR 7 , -OR 7 , -CONR 6 R 7 , -C0N(0R 9 )R 7 , C0 2 R 7 and -S ( 0 ) n R 13 , wherein Ci-Cβ alkyl, C 2 -C 6 alkenyl, C -C 6 alkynyl, C - CQ cycloalkyl and C4-C8 cycloalkylalkyl are substituted with 0 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, -N0 2 , halo, -CN, -NR 6 R 7 , COR 7 ' -OR 7 , -C0NR 6 R 7 , C0 2 R 7 and -S(0) n R 13 ; R6 and R7 are independently selected at each occurrence from H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, C4- C12 cycloalkylalkyl, aryl, aryl(Cι-C4 alkyl)-, heterocyclyl, heterocyclyl (C1-C4 alkyl)-, morpholinoethyl, morpholinopropyl and orpholinobutyl; or -NR 6 R 7 taken together as a whole is piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine or thiomorpholine; wherein C1 . -C4 alkyl, may be substituted with 0 to 2 substituents independently selected at each occurrence from -OH or C1-C4 alkoxy groups; R 8 is independently at each occurrence H or C1 . -C4 alkyl; R 9 and R 10 are independently at each occurrence selected from H, C1-C4 alkyl and C3-C6 cycloalkyl; R 11 is H, C1-C4 alkyl, C1-C4 haloalkyl, or C3-C6 cycloalkyl ; R 12 is C1-C4 alkyl, C1-C4 haloalkyl or -NR 6 R 7 ; R 13 is C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3- C6 cycloalkyl, C4-C12 cycloalkylalkyl, -NR 6 R 7 , aryl, aryl(Cι-C4 alkyl)-, heterocyclyl or heterocyclyl (Cι~ C4 alkyl ) - ,- R 14 is C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, C4-C12 cycloalkylalkyl, -NR 15 R 16 ; R 15 and R lf - > are independently selected at each occurrence from H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl and C4- C12 cycloalkylalkyl; or -NR 5 R 1 6 taken together as a whole is piperidine, pyrrolidine, piperazine, N-methyl-piperazine, morpholine or thiomorpholine; aryl is phenyl substituted with 0 to 3 substituents independently selected at each occurrence from C 1 -C 4 alkyl, halo, -CN, -OR 15 , -S(0) n R 14 , -COR 15 , -C02R 15 , -Nθ2, -NR 8 C0R 15 , -NR 8 CONR 15 R 16 , -NR 8 Cθ2R 15 and -NR 15 R 16 ; heterocyclyl is pyridyl, pyrimidinyl, triazinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl or pyrazolyl, each substituted with 0 to 3 substituents independently selected at each occurrence from C 1 -C4 alkyl, halo, -CN, -OR 15 , -S(0) n R 14 , -C02R 15 , -N02, -NR 8 COR 15 , -NR 8 CONR 15 R 16 , -NR 8 C02R 15 , and -NR 15 R 16 ; and n is independently at each occurrence 0 , 1 or 2. [4] More preferred compounds of this invention are compounds of Formula (I) and pharmaceutically acceptable salts and pro-drug forms thereof, wherein: Z is CR 2 ; Y is NR 4 ; Ar is phenyl or pyridyl, each substituted with 0 to 4 R 5 groups ; R 1 is H, halo, C1 . -C 4 alkyl, cyclopropyl, C1 . -C3 haloalkyl, -CN, -NR 6 R 7 , -CONR 6 R 7 , -COR 7 , -C0 2 R 7 , -OR 7 or -S(0) n R 13 wherein C1-C4 alkyl is substituted with 0 to 3 substituents independently selected at each occurrence from C3-C4 cycloalkyl, halo, -CN, -OR 7 , -S(0) n R 13 . -COR 7 , -C02R 7 , -NR 6 R 7 ; R 2 is H; R 3 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C4 haloalkyl or aryl, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or C3-C6 cycloalkyl is each substituted with 0 to 3 substituents independently selected at each occurrence from Ci-Cζ alkyl, C 3 -C 6 cycloalkyl, C 1 -C 4 haloalkyl, halo, -CN, -OR 7 , -S(0) n R 13 , -C0 2 R 7 , -NR 8 COR 7 , -NR 8 CONR 6 R 7 , -NR 8 C0 2 R 7 , -NR 6 R 7 and aryl; R 4 is H, allyl, or C1-C4 alkyl, wherein C1-C4 alkyl is optionally substituted with C1-C4 alkyl, -OR 7 , -S(0)2R 12 - -C02R 7 , -NR 6 R 7 or -NR 9 COR 10 ; R 5 is independently selected at each occurrence from C 1 -C 6 alkyl, aryl, heterocyclyl, C1 . -C 4 haloalkyl, halo, -CN, -N0 , -NR 6 R 7 , -COR 7 , -OR 7 , -CONR 6 R 7 , -CON(OR 9 )R 7 , -CO2R 7 and -S(0) n R 13 . wherein Ci-Ce alkyl is substituted with 0 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, -N0 , halo, -CN, -NR 6 R 7 , COR 7 ' -OR 7 , -CONR 6 R 7 , C0 2 R 7 and -S(0) n R 13 ; R6 and R7 are independently selected at each occurrence from H, C1-C4 alkyl, C1-C4 haloalkyl and C2-C8 alkoxyalkyl ; wherein C1-C4 alkyl, may be substituted with 0 to 2 substituents independently selected at each occurrence from -OH or C1-C4 alkoxy groups; R 8 , R 9 and R 10 are independently at each occurrence H or C1-C4 alkyl; R 12 and R 13 are independently at each occurrence C1-C4 alkyl or -NR 6 R 7 ; R 14 is C1-C4 alkyl or -NR 15 R 16 ; R 15 and R lf ^ are independently at each occurrence H, C1 . -C4 alkyl or C2-C8 alkoxyalkyl; aryl is phenyl substituted with 0 to 3 substituents independently selected at each occurrence from C 1 -C 4 alkyl, halo, -CN, -OR 15 , -S(0) n R 14 - -COR 15 , -CO2R 15 , -NO2 and -NR 15 R 16 , * and n is independently at each occurrence 0, 1 or 2. [5] Even more preferred compounds of this invention are compounds of Formula (I) and pharmaceutically acceptable salts and pro-drug forms thereof, wherein: Z is CR 2 ; Y is NR 4 ; Ar is phenyl or pyridyl, each substituted with 2 to 4 R 5 groups; R 1 is H, Cl, Br, methyl, ethyl, cyclopropyl, or -CN, R 2 is H; R 3 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1 . -C4 haloalkyl or aryl, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or C3-C6 cycloalkyl is each substituted with 0 to 3 substituents independently selected at each occurrence from C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, -CF 3 , halo, -CN, -OR 7 , and aryl; R 4 is H, methyl, ethyl, i-propyl, n-propyl, n-butyl, i-butyl, s-butyl, n-butyl, or allyl; R 5 is independently selected at each occurrence from methyl, ethyl, i-propyl, n-propyl, aryl, -CF 3 , halo, -CN, -N(CH 3 ) 2 , -C(=0)CH 3 , -OCH 3 , -OCH 2 CH 3 , -OCF 3 , and -S(0) 2 CH 3 ; R 14 is C1-C4 alkyl or -NR 15 R 16 ; R 15 and R l! ^ are independently at each occurrence H, C1-C4 alkyl or C2-C8 alkoxyalkyl; aryl is phenyl substituted with 0 to 3 substituents independently selected at each occurrence from C 1 -C 4 alkyl, halo, -CN, -OR 15 , -S(0) n R 14 , -COR 15 , -CO2R 15 , -NO2 and -NR 15 R 16 ; and n is independently at each occurrence 0, 1 or 2. [6] Specifically preferred compounds of this invention are compounds of Formula (I) , pharmaceutically acceptable salts and pro-drug forms thereof, which are: 3- [ (2 , 4-Dibromophenyl)amino] -5-chloro-l- (1- ethylpropyl) -2 (1H) -pyrazinone; 3- [ [2-Bromo-4- (1-methylethyl) phenyl] amino] -5-chloro-l- (1-ethylpropyl) -2 (1H) -pyrazinone; 3- [ (2, 4-Dibromophenyl) ethylamino] -5-chloro-l- (1- ethylpropyl) -2 (1H) -pyrazinone; 3- [ [2-Bromo-4- (1-methylethyl) phenyl] ethylamino] -5- chloro-1- (1-ethylpropyl) -2 (1H) -pyrazinone; 3- [ (2, 4, 6-Trimethylphenyl) amino] -5-chloro-l- (1- ethylpropyl) -2 (1H) -pyrazinone; 3- [ (2, 4, 6-Trimethylphenyl) ethylamino] -5-chloro-l- (1- ethylpropyl) -2 (1H) -pyrazinone; (+/-)-3-[(2,4, 6-Trimethylphenyl) amino] -5-chloro-l- [1- (methoxymethyl)propyl] -2 (1H) -pyrazinone; 3- [ (2-Bromo-4, 6-dimethoxyphenyl) amino] -5-chloro-l- (1- ethylpropyl) -2 (1H) -pyrazinone; 3- [ (2-Cyano-4, 6-dimethylphenyl) amino] -5-chloro-l- [1- (methoxymethyl)propyl] -2 (IH) -pyrazinone; (+/-) -3- [ (2-Bromo-4, 6-dimethoxyphenyl) amino] -5-chloro- 1- [1- (methoxymethyl)propyl] -2 (IH) -pyrazinone; (+/-) -3- [ (2-Chloro-4, 6-dimethoxyphenyl) amino] -5-chloro- 1- [1- (methoxymethyl)propyl] -2 (IH) -pyrazinone; (+/-) -3- [ (4, 6-Dimethyl-2-iodophenyl) amino] -5-chloro-l- [1- (methoxymethyl)propyl] -2 (IH) -pyrazinone; 3- [ (2-Cyano-4, 6-dimethylphenyl) amino] -5-chloro-l- [1- (methoxy ethyl)propyl] -2 (IH) -pyrazinone; (+/-) -3- [ (2-Bromo-4, 6-dimethylphenyl) amino] -5-chloro-l- [1- (methoxymethyl)propyl] -2 (IH) -pyrazinone; (+/-) -3- [ (4-Bromo-2, 6-dimethylphenyl) amino] -5-chloro-l- [1- (methoxymethyl)propyl] -2 (IH) -pyrazinone; (+/-) -3- [ (4-Acetyl-2 , 6-dimethylphenyl) amino] -5-chloro- 1- [1- (methoxymethyl)propyl] -2 (IH) -pyrazinone; (+/-) -3- [ (2-Acetyl-4, 6-dimethylphenyl) amino] -5-chloro- 1- [1- (methoxymethyl) propyl] -2 (IH) -pyrazinone; (+/-) -3- [ (4, 6-Dimethyl-2-thiomethylphenyl) amino] -5- chloro-l-[l- (methoxymethyl) propyl] -2 (IH) -pyrazinone; (+/-) -3- [ (4, 6-Dimethyl-2-methylsulfonylphenyl) amino] -5- chloro-1- [1- (methoxymethyl)propyl] -2 (IH) -pyrazinone; {+/-) -3- [ (4-Chloro-2-iodo-6-methylphenyl) amino] -5- chloro-1- [1- (methoxymethyl)propyl] -2 (IH) -pyrazinone; 3-[ (2, 4, 6-TrimethyIphenyl) amino] -5-chloro-l- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone; 3- [ (2,4, 6-Trimethylphenyl) amino] -5-chloro-l-phenyl- 2 (IH) -pyrazinone; (+/-) -3- [ (2, 4-Dibromophenyl)amino] -5-methyl-l- [1- (methoxymethyl)propyl] -2 (IH) -pyrazinone; (+/-) -3- [ [2-Bromo-4- (1-methylethyl) phenyl] amino] -5- methyl-1- [1- (methoxymethyl)propyl] -2 (IH) -pyrazinone; (+/-)-3-[(2,4, 6-Trimethylphenyl) amino] -5-methyl-l- [1- (me hoxymethyl)propyl] -2 (IH) -pyrazinon ,- 3-[ (2, 4, 6-Trimethylphenyl) amino] -5-methyl-l- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone; 3- [ (2 , 4-Dichloro-6-methylphenyl) amino] -5-methyl-l- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone; 3- [ (2, 4-Dichloro-6-methylphenyl)amino] -5-chloro-l- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone; 3- [ (2, 4-Dibromo-6-methylphenyl)amino] -5-chloro-l- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone; (+/-) -3- [ (2,4, 6-Trimethylphenyl) amino] -5-methyl-l- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) -pyrazinone; (+/-)-3-[(2,4, 6-Trimethylphenyl) amino] -5-chloro-l- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) -pyrazinone; 3-[ (2, 4, 6-Trimethylphenyl) amino] -5-chloro-l- [1- (2- methoxyethyl ) -3-methoxypropyl] -2 (IH) -pyrazinone; (+/-) -3- [ (2, 4-Dimethyl-6-methoxyphenyl) amino] -5-chloro- 1- [1- (methoxymethyl) propyl] -2 (IH) -pyrazinone; (+/-)-3-[(2, 4-Dimethyl-6-methoxyphenyl) amino] -5-chloro- 1- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) -pyrazinone; (+/-)-3-[(2, 4-Dimethyl-6-methoxyphenyl) amino] -5-methyl- 1- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) -pyrazinone; (+/-) -3- [ (4-Bromo-2 , 6-dimethylphenyl) amino] -5-methyl-1- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) -pyrazinone; (+/-) -3- [ (2-Chloro-4, 6-dimethylphenyl) amino] -5-methyl- 1- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) -pyrazinone; (+/-) -3- [ [2, 4-Dimethyl-6- (methoxymethyl) phenyl] amino] - 5-methyl-l- [1- (methoxymethyl) -3-methoxypropyl] -2 (1H)- pyrazinone; 3- [ (2, 4-Dimethyl-6-methoxyphenyl) mino] -5-methyl-l- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone; 3- [ (4-Bromo-2, 6-dimethylphenyl) amino] -5-methyl-l- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone; 3- [ (2-Chloro-4, 6-dimethylphenyl) amino] -5-methyl-l- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone; 3- [ [2, 4-Dimethyl-6- (methoxymethyl) henyl] amino] -5- methyl-1- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) - pyrazinone; (+/-) -3- [ (2, 4-Dimethyl-6-methoxyphenyl) amino] -5-chloro- 1- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) -pyrazinone; (+/-) -3- [ (4-Bromo-2 , 6-dimethylphenyl) amino] -5-chloro-l- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) -pyrazinone; (+/-) -3- [ (2-Chloro-4, 6-dimethylphenyl) amino] -5-chloro- 1- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) -pyrazinone; (+/-)-3-[[2, 4-Dimethyl-6- (methoxymethyl) phenyl] amino] - 5-chloro-l- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) - pyrazinone; 3- [ (2, 4-Dimethyl-6-methoxyphenyl) amino] -5-chloro-l- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone; 3- [ (4-Bromo-2, 6-dimethylphenyl) amino] -5-chloro-l- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone; 3- [ (2-Chloro-4, 6-dimethylphenyl) amino] -5-chloro-l- [1- (methoxymethyl ) -2-methoxyethyl] -2 (IH) -pyrazinone; 3- [ [2, 4-Dimethyl-6- (methoxymethyl) phenyl] amino] -5- chloro-1- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) - pyrazinone; (+/-) 3- [ (2, 4-Dimethyl-6-methoxyphenyl) amino] -5-chloro- 1- (2-methoxy-1-methylethyl) -2 (IH) -pyrazinone; (+/-)3- [ (4-Bromo-2, 6-dimethylphenyl) amino] -5-chloro-1- (2-methoxy-l-methylethyl) -2 (IH) -pyrazinone; (+/-)3- [ (4-Bromo-2, 6-dimethylphenyl ) amino] -5-chloro-l- [1- (ethoxymethyl) propyl] -2 (IH) -pyrazinone; (+/-) 3- [ (4-Bromo-2 , 6-dimethylphenyl) amino] -5-chloro-1- (2-ethoxy-l-methylethyl) -2 (IH) -pyrazinone; and (+/-) 3- [ (4-Bromo-2, 6-difluorophenyl ) amino] -5-chloro-1- [1- (methoxymethyl)propyl] -2 (IH) -pyrazinone; (+/-) -3- [ (2-Bromo-4, 6-dimethylphenyl) amino] -5-methyl-l- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) -pyrazinone; (+/-) -3- [ (2, 4-Dimethyl-6-thiomethylphenyl) amino] -5- methyl-1- [1- (methoxymethyl) -3-raethoxypropyl] -2 (IH) - pyrazinone; (+/-) -3- [ (2, 4-Dimethyl-6-methylsulfonylphenyl) amino] -5- methyl-1- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) - pyrazinone; (+/-) -3- [ (2, 6-Dimethyl-4- (N,N-dimethylamino) phenyl) - amino] -5-methyl-l- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) - pyrazinone; (+/-) -3- [ (2 , -Dichloro-6-methylphenyl) amino] -5-methyl- 1- [1- (methoxymethyl) -3-raethoxypropyl] -2 (IH) -pyrazinone; (+/-) -3- [ (4-Chloro-2, 6-dimethylphenyl) amino] -5-methyl- 1- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) -pyrazinone; (+/-) -3- [ (2, 6-Dimethyl-4-thiomethylphenyl) amino] -5- methyl-1- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) - pyrazinone; (+/-) -3- [ (2, 6-Dimethyl-4-methoxyphenyl) amino] -5-methyl- 1- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) -pyrazinone; (+/-)-3-[ (2, 6-Dimethyl-4-methylsulfonylphenyl) amino] -5- methyl-1- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) - pyrazinone; (+/-) -3- [ (4-Acetyl-2, 6-dimethylphenyl) amino] -5-methy1- 1- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) -pyrazinone; 3- [ (4-Bromo-2 , 6-dimethylphenyl) amino] -5-methyl-l- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone; 3- [ (4-Acetyl-2 , 6-dimethylphenyl) amino] -5-methyl-l- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone; 3-[ (2, 6-Dimethyl-4-thiomethylphenyl) amino] -5-methyl-l- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone; 3- [ (2, 6-Dimethyl-4-methylsulfonylphenyl) amino] -5- methyl-1- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) - pyrazinone; 3- [ (2 , 6-Dimethyl-4- (N,N-dimethylamino) phenyl) amino] -5- methyl-1- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) - pyrazinone; 3- [ (4, 6-Dimethyl-2- (N,N-dimethylamino) phenyl) amino] -5- methyl-1- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) - pyrazinone; (+/-)3-[ (2,6-Dimethyl-4-thiomethylphenyl)amino]-5- chloro-1- [1- (methoxymethyl) propyl] -2 (IH) -pyrazinone; (+/-) 3- [ (2 , 6-Dimethyl-4-methylsulfonylphenyl)amino] -5- chloro-1- [1- (methoxymethyl)propyl] -2 (IH) -pyrazinone; (+/-) 3- [ (2-Chloro-4, 6-dimethylphenyl) amino] -5-chloro-l- [1- (methoxymethyl) propyl] -2 (IH) -pyrazinone; ( +/-) 3- [ (4-Bromo-6-methoxy-2-methylphenyl) amino] -5- chloro-1- [1- (methoxymethyl) propyl] -2 (IH) -pyrazinone; 3- [ (2 , 6-Dimethyl-4-thiomethylphenyl) amino] -5-chloro-l- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone; 3- [ (2, 6-Dimethyl-4-methylsulfonylphenyl) amino] -5- chloro-1- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) - pyrazinone; 3- [ (4-Bromo-6-methoxy-2-methylphenyl) amino] -5-chloro-l- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone; and 3- [ (2,4, 6-Trimethylphenyl) amino] -5-methyl-l- (1- ethylpropyl ) -2 ( IH) -pyrazinone . [7] A second embodiment of preferred compounds of this invention are compounds of Formula (I) and pharmaceutically acceptable salts and pro-drug forms thereof, wherein: Z is CR 2 ; Y is NR 4 or 0; Ar is phenyl or pyridyl, each substituted with 0 to 4 R 5 groups; R 1 is H, halo, Ci-Cio alkyl, C2-C10 alkenyl, C2- C10 alkynyl, C3-C8 cycloalkyl, C1-C4 haloalkyl, aryl, heterocyclyl, -CN, -OR 7 , -SH, -S(0) n R 13 . -COR 7 , -CONR 6 R 7 , -CO2R 7 , -0C(0)R 13 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , -NR 8 C02R 7 , or -NR 6 R 7 , wherein C1 . -C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl or C3-C8 cycloalkyl is each substituted with 0 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, -CN, -OR 7 , -SH, -S(0) n R 13 , -COR 7 , -C02R 7 , -OC(0)R 13 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , -NR 8 C02R 7 , -NR 6 R 7 , -CONR 6 R 7 , aryl and heterocyclyl; R 2 is H, C 1 -C 4 alkyl, halo, C 1 -C 4 haloalkyl; R 3 is C 1 -C 4 alkyl, C3-C6 cycloalkyl, C 1 -C 4 haloalkyl and -NR 6 R 7 , wherein C1-C4 alkyl is substituted with 0 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, halo, -CN, -OR 7 , -S(0)nR 13 . -COR 7 , -CO2R 7 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , -NR 8 C02R 7 , -NR 6 R 7 and -C0NR 6 R 7 ; R 4 is H, C1-C6 alkyl or C2-C6 alkenyl, wherein C -Cβ alkyl is optionally substituted with C1-C4 alkyl, C1 . -C4 haloalkyl, -OR 7 , -S(0) n R 12 , -CO2R 7 , -NR 6 R 7 or -NR 9 COR 10 ; R 5 is independently selected at each occurrence from l-Cio alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C6 cycloalkyl, C4-C12 cycloalkylalkyl, aryl, heterocyclyl, -Nθ2 , halo, -CN, C1-C4 haloalkyl, -NR 6 R 7 , -NR 8 COR 7 , -NR 8 Cθ 2 R 7 , -OR 7 , -COR 7 , -CO2R 7 , -CONR 6 R 7 , -CON(OR 9 )R 7 and -S(0) n R 13 , wherein C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C6 cycloalkyl and C4-C12 cycloalkylalkyl are substituted with 0 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, -Nθ2 - halo, -CN, -OR 7 , -COR 7 , -C02R 7 , -CONR 6 R 7 , -NR 6 R 7 , -NR 8 COR 7 , -NR 8 C0 2 R 7 and -S(0) n R 13 ; R-5 and R 7 are independently selected at each occurrence from H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, C4- C12 cycloalkylalkyl, aryl, aryl(Cι_-C4 alkyl)-, heterocyclyl, heterocyclyl (C3 . -C4 alkyl)-, morpholinoethyl, morpholinopropyl and morpholinobutyl; or -NR 6 R 7 taken together as a whole is piperidine, pyrrolidine, piperazine, N-methyl- piperazine, morpholine or thiomorpholine; wherein C1.-C4 alkyl, may be substituted with 0 to 2 substituents independently selected at each occurrence from -OH or C3 . -C4 alkoxy groups ; R 8 is independently at each occurrence H or C1-C4 alkyl; R 9 and R u are independently at each occurrence selected from H, C1-C4 alkyl and C3-C6 cycloalkyl; R 11 is H, C1-C4 alkyl, C1 . -C4 haloalkyl, or C3-C6 cycloalkyl; R 12 is C1-C4 alkyl, C1-C4 haloalkyl or -NR 6 R 7 ; R 13 is C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, C4-C12 cycloalkylalkyl, -NR 6 R 7 , aryl, aryl(Cι-C4 alkyl)-, heterocyclyl or heterocyclyl (C1-C4 alkyl ) - ; R 14 is C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, C4-C12 cycloalkylalkyl, -NR 15 R 16 ; R 15 and R lf ^ are independently selected at each occurrence from H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl and C4- C12 cycloalkylalkyl; or -NR 15 R 16 taken together as a whole is piperidine, pyrrolidine, piperazine, N-methyl-piperazine, morpholine or thiomorpholine; aryl is phenyl or naphthyl, each substituted with 0 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, halo, -CN, -OR 15 , -S(0) n R 14 . -COR 15 , -C02R 15 , -N02 , -NR 8 COR 15 , -NR 8 CONR 15 R 16 , -NR 8 C02R 15 and -NR 15 R 16 ; heterocyclyl is pyridyl, pyrimidinyl, triazinyl, furanyl, thienyl, imidazolyl, thiazolyl , pyrrolyl, oxazolyl, isoxazolyl or pyrazolyl, each substituted with 0 to 3 substituents independently selected at each occurrence from C 1 -C 4 alkyl, halo, -CN, -OR 15 , -S(0) n R 14 , -C02R 15 , -N02 , -NR 8 COR 15 , -NR 8 CONR 15 R 16 , -NR 8 C02R 15 , and -NR 15 R 16 ; and n is independently at each occurrence 0, 1 or 2. [8] More preferred compounds of the second embodiment of this invention are compounds of Formula (I) and pharmaceutically acceptable salts and pro-drug forms thereof, wherein: Z is CR 2 ; Y is NR 4 ; Ar is phenyl or pyridyl, each substituted with 0 to 4 R 5 groups ; R 1 is H, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, aryl, heterocyclyl, -CN, -OR 7 , -Ξ(0) n R 13 . -COR 7 , -CONR 6 R 7 , -C02R 7 or -NR 6 R 7 , wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or C3-C6 cycloalkyl is each substituted with 0 to 3 substituents independently selected at each occurrence from C3 . -C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, -CN, -OR 7 , -SH, -S(0) n R 13 , -COR 7 , -C02R 7 , -OC(0)R 13 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , -NR 8 C02R 7 , -NR 6 R 7 , -CONR 6 R 7 , aryl and heterocyclyl; R 2 is H; R 3 is C 1 -C 4 alkyl, C3-C6 cycloalkyl, C 1 -C 4 haloalkyl and -NR 6 R 7 , wherein C1-C4 alkyl is substituted with 0 to 3 substituents independently selected at each occurrence from C3-C6 cycloalkyl, C1-C4 haloalkyl, halo, -CN, -OR 7 , -S(0) n R 13 , -COR 7 , -CO2R 7 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , -NR 8 Cθ2R 7 , -NR 6 R 7 and -CONR 6 R 7 ; R 4 is H, allyl, or C1-C4 alkyl, wherein C1-C4 alkyl is optionally substituted with C1-C4 alkyl, -OR 7 , -S(0)2R 12 i -CO2R 7 , -NR β R 7 or -NR 9 COR 10 ; R 5 is independently selected at each occurrence from i-C δ alkyl, aryl, heterocyclyl, C 1 -C 4 haloalkyl, halo, -CN, -N0 2 , -NR 6 R 7 , -COR 7 , -OR 7 , -CONR 6 R 7 , -CON(OR 9 )R 7 , -C0 2 R 7 and -S(0) n R 13 . wherein Cι-C 6 alkyl is substituted with 0 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, -N0 , halo, -CN, -NR 6 R 7 , COR 7 ' -OR 7 , -CONR 6 R 7 , C0 2 R 7 and -S(0) n R 13 ; R6 and R7 are independently selected at each occurrence from H, C1-C4 alkyl, C1 . -C4 haloalkyl and C2-C8 alkoxyalkyl ; wherein C1-C4 alkyl, may be substituted with 0 to 2 substituents independently selected at each occurrence from -OH or C1-C4 alkoxy groups ; R 8 , R 9 and R 10 are independently at each occurrence H or C1-C4 alkyl; R 12 and R 13 are independently at each occurrence C1-C4 alkyl or -NR 6 R 7 ; R 14 is C1-C4 alkyl or -NR 15 R 16 ; R 15 and R 1 '*' are independently at each occurrence H, C1-C4 alkyl or C2-C8 alkoxyalkyl; aryl is phenyl substituted with 0 to 3 substituents independently selected at each occurrence from C 1 -C 4 alkyl, halo, -CN, -OR 15 , -S(0) n R 14 , -COR 15 , -CO2R 15 . -NO2 and -NR 15 R 16 ; and n is independently at each occurrence 0, 1 or 2. [10] A third embodiment of preferred compounds of this invention are compounds of Formula (I) and pharmaceutically acceptable salts and pro-drug forms thereof, wherein: Z is N; Y is NR 4 or 0; Ar is phenyl or pyridyl, each substituted with 0 to 4 R 5 groups ; R 1 is H, halo, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, aryl, -CN, C1-C4 haloalkyl, -NR 6 R 7 , -CONR 6 R 7 , -OR 7 , -COR 7 , -C0 2 R 7 or -S(0) n R 13 , wherein C1 . -C4 alkyl is substituted with 0 to 3 substituents independently selected at each occurrence from C1 . -C3 alkyl, C3-C6 cycloalkyl, halo, -CN, -OR 7 , -S(0)nR 13 , -COR 7 , -CO2R 7 , -NR 8 COR 7 , -NR 8 C02R 7 , -NR 6 R 7 and aryl; R 3 is C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C8 cycloalkyl, C1-C4 haloalkyl, aryl, heterocyclyl, -CN, -S(0)2R 13 , -COR 7 , -CO2R 7 or -CONR 6 R 7 , wherein C1 . -C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl or C3-C8 cycloalkyl is each substituted with 0 to 3 substituents independently selected at each occurrence from Ci-Cβ alkyl, C 3 -C 6 cycloalkyl, C 1 -C 4 haloalkyl, halo, -CN, -OR 7 , -S(0) n R 13 , -C0 2 R 7 , -NR 8 C0R 7 , -NR 8 CONR 6 R 7 , -NR 8 C0 2 R 7 , -NR 6 R 7 , aryl and heterocyclyl ; R 4 is H, C1-C6 alkyl or C2-C6 alkenyl, wherein C1-C6 alkyl is optionally substituted with C1-C4 alkyl, C3-C6 cycloalkyl, C1 . -C4 haloalkyl, -OR 7 , -S(0) n R 12 , -CO2R 7 , -NR 6 R 7 or -NR 9 COR 10 ; R 5 is independently selected at each occurrence from Cι-C 6 alkyl, C -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C4-C8 cycloalkylalkyl, aryl, heterocyclyl, C 1 -C 4 haloalkyl, halo, -CN, -N0 , -NR 6 R 7 , -COR 7 , -OR 7 , -C0NR 6 R 7 , -CON(OR 9 )R 7 , C0 2 R 7 and wherein Ci-Cβ alkyl, C -C δ alkenyl, C -C 6 alkynyl, C 3 - C 6 cycloalkyl and C4-C8 cycloalkylalkyl are substituted with 0 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, -N0 2 , halo, -CN, -NR 6 R 7 , COR 7 - -OR 7 , -CONR 5 R 7 , C0 2 R 7 and -S ( 0 ) n R 13 ; R6 and R7 are independently selected at each occurrence from H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, C4- C12 cycloalkylalkyl, aryl, aryl(Cχ-C4 alkyl)-, heterocyclyl , heterocyclyl (C1-C4 alkyl ) - , morpholinoethyl, morpholinopropyl and morpholinobutyl; or -NR 6 R 7 taken together as a whole is piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine or thiomorpholine; wherein C1-C4 alkyl, may be substituted with 0 to 2 substituents independently selected at each occurrence from -OH or C1-C4 alkoxy groups; R 8 is independently at each occurrence H or C1-C4 alkyl; R 9 and R 10 are independently at each occurrence selected from H, C1-C4 alkyl and C3-C6 cycloalkyl; R 11 is H, C1-C4 alkyl, C1-C4 haloalkyl, or C3-C6 cycloalkyl; R 12 is C1-C4 alkyl, C1-C4 haloalkyl or -NR 6 R 7 ,- R 13 is C1-C4 alkyl, C1 . -C4 haloalkyl, C2-C8 alkoxyalkyl, C3- C6 cycloalkyl, C4-C12 cycloalkylalkyl, -NR 6 R? , aryl, aryl (C1-C4 alkyl)-, heterocyclyl or heterocyclyl (Cι~ C4 alkyl ) - ; R 14 is C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, C4-C12 cycloalkylalkyl, -NR 15 R 16 ; R 15 and R 1 ^ are independently selected at each occurrence from H, C1-C4 alkyl, C1 . -C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl and C4- C12 cycloalkylalkyl; or -NR 15 R 16 taken together as a whole is piperidine, pyrrolidine, piperazine, N-methyl-piperazine, morpholine or thiomorpholine; aryl is phenyl substituted with 0 to 3 substituents independently selected at each occurrence from C 1 -C 4 alkyl, halo, -CN, -OR 15 , -S(0) n R 14 . -COR 15 , -Cθ2R 15 , -Nθ2, -NR 8 COR 15 , -NR 8 CONR 15 R lβ , -NR 8 Cθ2R 15 and -NR 15 R 16 ; heterocyclyl is pyridyl, pyrimidinyl, triazinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl or pyrazolyl, each substituted with 0 to 3 substituents independently selected at each occurrence from C1 . -C 4 alkyl, halo, -CN, -OR 15 , -S(0) n R 14 , -C02R 15 , - θ2, -NR 8 COR 15 , -NR 8 CONR 15 R 16 , -NR 8 Cθ2R 15 , and -NR 15 R 16 ; and n is independently at each occurrence 0, 1 or 2. [11] More preferred compounds of the third embodiment of this invention are compounds of Formula (I) and pharmaceutically acceptable salts and pro-drug forms thereof, wherein: Z is N; Y is NR 4 ; Ar is phenyl or pyridyl, each substituted with 0 to 4 R 5 groups ; R 1 is H, halo, C1 . -C 4 alkyl, C1-C3 haloalkyl, cyclopropyl, -CN, -NR 6 R 7 , -CONR 6 R 7 , -COR 7 , -C0 2 R 7 , -OR 7 or -S(0) n R 13 wherein C1-C4 alkyl is substituted with 0 to 3 substituents independently selected at each occurrence from C3-C4 cycloalkyl, halo, -CN, -OR 7 , -S(0) n R 13 , -COR 7 , -C02R 7 , -NR 6 R 7 ; R 3 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1 . -C4 haloalkyl or aryl, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or C3-C6 cycloalkyl is each substituted with 0 to 3 substituents independently selected at each occurrence from Ci-Cβ alkyl, C 3 -C 6 cycloalkyl, C 1 -C4 haloalkyl, halo, -CN, -OR 7 , -S(0) n R 13 / -C0 2 R 7 , -NR 8 C0R 7 , -NR 8 CONR 6 R 7 , -NR 8 C0 2 R 7 , -NR 6 R 7 and aryl; R 4 is H, allyl, or C1-C4 alkyl, wherein C1-C4 alkyl is optionally substituted with C1-C4 alkyl, -OR 7 , -S(0)2R 12 < -CO2R 7 , -NR 6 R 7 or -NR 9 COR 10 ; R 5 is independently selected at each occurrence from C 1 -C 6 alkyl, aryl, heterocyclyl, C 1 -C 4 haloalkyl, halo, -CN, -N0 2 , -NR 6 R 7 , -COR 7 , -OR 7 , -CONR 6 R 7 , -CON(OR 9 )R 7 , -C0 2 R 7 and -S(0) n R 13 , wherein Cι-C 6 alkyl is substituted with 0 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, -N0 2 , halo, -CN, -NR 6 R 7 , COR 7 ' -OR 7 , -CONR 6 R 7 , C0 2 R 7 and -S(0) n R 13 ; R^ and R7 are independently selected at each occurrence from H, C1-C4 alkyl, C1-C4 haloalkyl and C2-C8 alkoxyalkyl ; wherein C1.-C4 alkyl, may be substituted with 0 to 2 substituents independently selected at each occurrence from -OH or C1-C4 alkoxy groups; R 8 , R 9 and R 10 are independently at each occurrence H or C1-C4 alkyl; R 12 and R 13 are independently at each occurrence C1-C4 alkyl or -NR 6 R 7 ; R 14 is C1-C4 alkyl or -NR 15 R 16 ; R 15 and R ( 5 are independently at each occurrence H, C1-C4 alkyl or C2-C8 alkoxyalkyl; aryl is phenyl substituted with 0 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, halo, -CN, -OR 15 , -S(0) n R 14 , -COR 15 , -CO2R 15 , -N02 and -NR 15 R 16 ,- and n is independently at each occurrence 0, 1 or 2. [12] Even more preferred compounds of this invention are compounds of Formula (I) and pharmaceutically acceptable salts and pro-drug forms thereof, wherein: Z is N; Y is NR 4 ; Ar is phenyl or pyridyl, each substituted with 2 to 4 R 5 groups ; R 1 is H, methyl, ethyl, cyclopropyl, -CF 3 , or -N(CH 3 ) 2 ; R 3 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C4 haloalkyl or aryl, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or C3-C6 cycloalkyl is each substituted with 0 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, C 3 -Cβ cycloalkyl, -CF 3 , halo, -CN, -OR 7 , and aryl; R 4 is H, methyl, ethyl, i-propyl, n-propyl, n-butyl, i-butyl, s-butyl, n-butyl, or allyl; R 5 is independently selected at each occurrence from methyl, ethyl, i-propyl, n-propyl, aryl, -CF 3 , halo, -CN, -N(CH 3 ) , -C(=0)CH 3 , -OCH3, -OCH-2CH3, -OCF3, and -S(0) 2 CH 3 ; R 14 is C1-C4 alkyl or -NR 15 R 16 ; R 15 and R 16 are independently at each occurrence H, C1-C4 alkyl or C2-C8 alkoxyalkyl; aryl is phenyl substituted with 0 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, halo, -CN, -OR 15 , -S(0) n R 14 , -COR 15 , -CO2R 15 , -N02 and -NR 15 R 16 ; and n is independently at each occurrence 0, 1 or 2. [13] A fourth embodiment of preferred compounds of this invention are compounds of Formula (I) and pharmaceutically acceptable salts and pro-drug forms thereof, wherein: Z is N; Y is NR 4 or 0; Ar is phenyl or pyridyl, each substituted with 0 to 4 R 5 groups ; R 1 is H, halo, Ci-Cio alkyl, C2-C10 alkenyl, C2- C10 alkynyl, C3-C8 cycloalkyl, C1-C4 haloalkyl, aryl, heterocyclyl, -CN, -OR 7 , -SH, -S(0) n R 13 , -COR 7 , -CONR 6 R 7 , -CO2R 7 , -0C(0)R 13 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , -NR 8 C02R 7 , or -NR 6 R 7 , wherein Cι-Cχo alkyl, C2-C10 alkenyl, C2-C10 alkynyl or C3-C8 cycloalkyl is each substituted with 0 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, -CN, -OR 7 , -SH, -S(0) n R 13 , -COR 7 , -C02R 7 , -OC(0)R 13 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , -NR 8 C02R 7 , -NR 6 R 7 , -CONR 6 R 7 , aryl and heterocyclyl; R 3 is C 1 -C 4 alkyl, -CN, C3-C6 cycloalkyl, C 1 -C 4 haloalkyl, -OR 7 , -COR 7 , -C0 2 R 7 or -CONR 6 R 7 , wherein C1-C4 alkyl is substituted with 0 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, halo, -CN, -OR 7 , -S(0) n R 13 / -COR 7 , -CO2R 7 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , -NR 8 Cθ2R 7 , -NR 6 R 7 and -CONR 6 R 7 ; R 4 is H, C1-C6 alkyl or C2-C6 alkenyl, wherein C1-C6 alkyl is optionally substituted with C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, -OR 7 , -S(0) n R 12 , -CO2R 7 , -NR 6 R 7 or -NR 9 COR 10 ; R 5 is independently selected at each occurrence from 1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C6 cycloalkyl, C4-C12 cycloalkylalkyl, aryl, heterocyclyl, -NO2 , halo, -CN, C1-C4 haloalkyl, -NR 6 R 7 , -NR 8 COR 7 , -NR 8 C0 2 R 7 , -OR 7 , -COR 7 , -C02R 7 , -CONR 6 R 7 , -CON(OR 9 )R 7 and -S(0) n R 13 . wherein C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C6 cycloalkyl and C4-C12 cycloalkylalkyl are substituted with 0 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, -NO2 , halo, -CN, -OR 7 , -COR 7 , -CO2R 7 , -CONR 6 R 7 , -NR 6 R 7 , -NR 8 COR 7 , -NR 8 C0 R 7 and -S(0) n R 13 ; R- * and R7 are independently selected at each occurrence from H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, C4- C12 cycloalkylalkyl, aryl, aryl(Cχ-C4 alkyl)-, heterocyclyl, heterocyclyl (C1-C4 alkyl)-, morpholinoethyl, morpholinopropyl and morpholinobutyl; or NR 6 R 7 taken together as a whole is piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine or thiomorpholine; wherein C1-C4 alkyl, may be substituted with 0 to 2 substituents independently selected at each occurrence from -OH or C1-C4 alkoxy groups,* R 8 is independently at each occurrence H or C1-C4 alkyl; R 9 and R lu are independently at each occurrence selected from H, C1-C4 alkyl and C3-C6 cycloalkyl; R 11 is H, C1-C4 alkyl, C1-C4 haloalkyl, or C3-C6 cycloalkyl; R 12 is C1-C4 alkyl, C1-C4 haloalkyl or -NR 6 R 7 ; R 13 is C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, C4-C12 cycloalkylalkyl, -NR 6 R 7 , aryl, aryl (C1 . -C4 alkyl)-, heterocyclyl or heterocyclyl (C1-C4 alkyl)-; R 14 is C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, C4-C12 cycloalkylalkyl, -NR 15 R 16 ; R 15 and R 1( ^ are independently selected at each occurrence from H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl and C4- C12 cycloalkylalkyl; or -NR 15 R 1( -* i taken together as a whole is piperidine, pyrrolidine, piperazine, N-methy1-piperazine, morpholine or thiomorpholine; aryl is phenyl or naphthyl, each substituted with 0 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, halo, -CN, -OR 15 , -S(0) n R 14 . -COR 15 , -C02R 15 , -N02 , -NR 8 COR 15 , -NR 8 CONR 15 R 16 , -NR 8 C02R 15 and -NR 15 R 16 ; heterocyclyl is pyridyl, pyrimidinyl, triazinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl or pyrazolyl, each substituted with 0 to 3 substituents independently selected at each occurrence from C 1 -C 4 alkyl, halo, -CN, -OR 15 , -S(0) n R 14 , -C02R 15 , -Nθ2 , -NR 8 COR 15 , -NR 8 CONR 15 R 16 , -NR 8 C02R 15 , and -NR 15 R 16 ; and n is independently at each occurrence 0, 1 or 2. [14] More preferred compounds of the fourth embodiment of this invention are compounds of Formula (I) and pharmaceutically acceptable salts and pro-drug forms thereof, wherein: Z is N; Y is NR 4 ; Ar is phenyl or pyridyl, each substituted with 0 to 4 R 5 groups; R 1 is H, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1.-C4 haloalkyl, aryl, heterocyclyl, -CN, -OR 7 , -S(0) n R 13 , -COR 7 , -CONR 6 R 7 , -CO2R 7 or -NR 6 R 7 , wherein Ci-Cβ alkyl, C2-C6 alkenyl, C2-C6 alkynyl or C3-C6 cycloalkyl is each substituted with 0 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, -CN, -OR 7 , -SH, -S(0) n R 13 , -COR 7 , -C02R 7 , -OC(0)R 13 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , -NR 8 C02R 7 , -NR 6 R 7 , -CONR 6 R 7 , aryl and heterocyclyl; R 3 is C3.-C4 alkyl, -CN, C3-C6 cycloalkyl, C1-C4 haloalkyl, -OR 7 , -COR 7 or -C0 2 R 7 , wherein C1-C4 alkyl is substituted with 0 to 3 substituents independently selected at each occurrence from C3-C6 cycloalkyl, C1-C4 haloalkyl, halo, -CN, -OR 7 , -S(0) n R 13 , -COR 7 , -CO2R 7 , -NR 8 COR 7 , -NR 6 R 7 and -CONR 6 R 7 ; R 4 is H, allyl, or C1-C4 alkyl, wherein C1-C4 alkyl is optionally substituted with C1 . -C4 alkyl, -OR 7 , -S(0)2R 12 . -C02R 7 , -NR β R 7 or -NR 9 COR 10 ; R 5 is independently selected at each occurrence from C1-C6 alkyl, aryl, heterocyclyl, C1-C4 haloalkyl, halo, -CN, -N0 2 , -NR 6 R 7 , -COR 7 , -OR 7 , -CONR 6 R 7 , -CON(OR 9 )R 7 , -C0 R 7 and -S(0) n R 13 , wherein Cι-C 6 alkyl is substituted with 0 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, -N0 2 , halo, -CN, -NR 6 R 7 , COR 7 ' -OR 7 , -CONR 6 R 7 , C0 2 R 7 and -S(0) n R 13 ; R^ and R7 are independently selected at each occurrence from H, C1-C4 alkyl, C1-C4 haloalkyl and C2-C8 alkoxyalkyl ; wherein C1-C4 alkyl, may be substituted with 0 to 2 substituents independently selected at each occurrence from -OH or C1-C4 alkoxy groups; R 8 , R 9 and R 10 are independently at each occurrence H or C1-C4 alkyl; R 12 and R 13 are independently at each occurrence C1-C4 alkyl or -NR 6 R 7 ; R 14 is C1-C4 alkyl or -NR 15 R 16 ; R 15 and R 1 ^ are independently at each occurrence H, C1-C4 alkyl or C2-C8 alkoxyalkyl; aryl is phenyl substituted with 0 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, halo, -CN, -OR 15 , -S(0) n R 14 , -COR 15 , -CO2R 15 , -NO2 and -NR 15 R 16 ; and n is independently at each occurrence 0, 1 or 2. A fifth embodiment of this invention is the method of treating affective disorders, anxiety, depression, post- traumatic stress disorders, supranuclear palsy, seizure disorders, stroke, irritable bowel syndrome, immune suppression, Alzheimer's disease, gastrointestinal disease, anorexia nervosa or other eating disorders, drug or alcohol withdrawal symptoms, drug addiction, inflammatory disorders, or fertility problems in a mammal in need of such treatment comprising administering to the mammal a therapeutically effective amount of a compound of Formula I. A sixth embodiment of this invention are pharmaceutical compositions comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of Formula I . This invention also includes intermediate compounds useful in preparation of the CRF antagonist compounds and processes for making those intermediates, as described in the following description and claims. The CRF antagonist compounds provided by this invention (and especially labelled compounds of this invention) are also useful as standards and reagents in determining the ability of a potential pharmaceutical to bind to the CRF receptor. DETAILED DESCRIPTION OF INVENTION Many compounds of this invention have one or more asymmetric centers or planes. Unless otherwise indicated, all chiral (enantiomeric and diastereomeric) and racemic forms are included in the present invention. Many geometric isomers of olefins, C=N double bonds, and the like can also be present in the compounds, and all such stable isomers are contemplated in the present invention. The compounds may be isolated in optically active or racemic forms. It is well known in the art how to prepare optically active forms, such as by resolution of racemic forms or by synthesis from optically active starting materials. All chiral, (enantiomeric and diastereomeric) and racemic forms and all geometric isomeric forms of a structure are intended, unless the specific stereochemistry or isomer form is specifically indicated. The terra "alkyl" includes both branched and straight- chain alkyl having the specified number of carbon atoms. For example, the term "Ci-Cio alkyl" denotes alkyl having 1 to 10 carbon atoms; thus, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl and decyl, wherein, for example, butyl can be -CH 2 CHCH 2 CH 3 , -CH 2 CH(CH 3 ) 2 , -CH(CH 3 )CH 2 CH 3 or -CH(CH 3 ) 3 . The term "alkenyl" includes hydrocarbon chains of either a straight or branched configuration and one or more unsaturated carbon-carbon bonds which may occur in any stable point along the chain. For example, the term "C2- C10 alkenyl" denotes alkenyl having 2 to 10 carbon atoms; thus , ethenyl , propenyl , butenyl , pentenyl , hexenyl , heptenyl, octenyl, nonenyl and decenyl, such as allyl, propargyl, l-buten-4-yl, 2-buten-4-yl and the like, wherein, for example, butenyl can be, but is not limited to, -CH=CH 2 CH 2 CH 3 , -CH 2 CH=CHCH 3 , -CH 2 CH 2 CH=CH 2 , -CH=C(CH 3 ) 2 or -CH=CHCH=CH 2 . The term "alkynyl" includes hydrocarbon chains of either a straight or branched configuration and one or more triple carbon-carbon bonds which may occur in any stable point along the chain. The term "C 2 -C 1 0 alkynyl" denotes alkynyl having 2 to 10 carbon atoms; thus, ethynyl, propynyl, butynyl, pentynyl, hexynyl , heptynyl , octynyl, nonynyl and decynyl . The term "haloalkyl" is intended to include both branched and straight-chain alkyl having the specified number of carbon atoms, substituted independently with 1 or more halogen, such as, but not limited to, -CH 2 F, -CHF , -CF 3 , -CF 2 Br, -CH 2 CF 3 , -CF 2 CF 3 , -CH(CF 3 ) 2 and the like. The term "alkoxy" represents an alkyl group of indicated number of carbon atoms attached through an oxygen bridge . The term "cycloalkyl" is intended to include saturated ring groups having the specified number of carbon, atoms, including mono-, bi- or poly-cyclic ring systems, such as cyclopropyl (c-Pr) , cyclobutyl (c-Bu) , cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, [3.3.0]bicyclooctyl, [2.2.2]bicyclooctyl and so forth. As used herein, the term "heterocyclyl" or "heterocyclic" is intended to mean a stable 5- to 7- membered monocyclic or bicyclic or 7- to 10-membered bicyclic heterocyclic ring which may be saturated, partially unsaturated, or aromatic, and which consists of carbon atoms and from 1 to 4 heteroatoms independently selected from the group consisting of N, 0 and S and wherein the nitrogen and sulfur heteroatoms may optionally be oxidized, and the nitrogen may optionally be quaternized, and including any bicyclic group in which any of the above-defined heterocyclic rings is fused to a benzene ring. The heterocyclic ring may be attached to its pendant group at any heteroatom or carbon atom which results in a stable structure. The heterocyclic rings described herein may be substituted on carbon or on a nitrogen atom if the resulting compound is stable. Examples of such heterocycles include, but are not limited to, pyridyl (pyridinyl) , pyrimidinyl, furanyl (furyl), thiazolyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, tetrazolyl, benzofuranyl, benzothiophenyl, indolyl, indolenyl, isoxazolinyl, isoxazolyl, quinolinyl, isoquinolinyl, benzimidazolyl, piperidinyl, 4- piperidonyl, pyrrolidinyl, 2-pyrrolidonyl, pyrrolinyl, tetrahydrofuranyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl or octahydroisoquinolinyl, azocinyl, triazinyl, 6H-1,2,5- thiadiazinyl, 2H, 6H-1 , 5, 2-dithiazinyl , thianthrenyl , pyranyl, isobenzofuranyl, chromenyl, xanthenyl , phenoxathiinyl, 2H-pyrrolyl, pyrrolyl, imidazolyl, pyrazolyl, isothiazolyl, isoxazolinyl, isoxazolyl, oxazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolizinyl, isoindolyl, 3H-indolyl, indolyl, 1H- indazolyl, purinyl, 4H-quinolizinyl, isoquinolinyl, quinolinyl, phthalazinyl, naphthyridinyl , quinoxalinyl , quinazolinyl, cinnolinyl, pteridinyl, 4aH-carbazole, carbazole, β-carbolinyl, phenanthridinyl , acridinyl, perimidinyl, phenanthrolinyl, phenazinyl, phenarsazinyl, phenothiazinyl , furazanyl, phenoxazinyl, isochromanyl, chromanyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, piperidinyl, piperazinyl, indolinyl, isoindolinyl, quinuclidinyl, morpholinyl, oxazolidinyl, benzothienyl, 2 , 3 -dihydrobenzofuranyl or 2 , 3 -dihydrobenzothienyl . The term "halo" or "halogen" includes fluoro, chloro, bromo and iodo . The term "substituted", as used herein, means that one or more hydrogen on the designated atom is replaced with a selection from the indicated group, provided that the designated atom's normal valency is not exceeded, and that the substitution results in a stable compound. When a substituent is keto (i.e., =0), then 2 hydrogens on the atom are replaced. Combinations of substituents and/or variables are permissible only if such combinations result in stable compounds. By "stable compound" or "stable structure" is meant a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and formulation into an efficacious therapeutic agent . The term "pharmaceutically acceptable salts" includes acid or base salts of the compounds of formula (I) . Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. Pharmaceutically acceptable salts of the compounds of the invention can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two; generally, nonaqueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. Lists of suitable salts are found in Remington's Pharmaceutical Sciences, 17th ed. , Mack Publishing Company, Easton, PA, 1985, p. 1418, the disclosure of which is hereby incorporated by reference. "Prodrugs" are considered to be any covalently bonded carriers which release the active parent drug of formula (I) in vivo when such prodrug is administered to a mammalian subject. Prodrugs of the compounds of formula (I) are prepared by modifying functional groups present in the compounds in such a way that the modifications are cleaved, either in routine manipulation or in vivo, to the parent compounds. Prodrugs include compounds wherein hydroxy, amine, or sulfhydryl groups are bonded to any group that, when administered to a mammalian subject, cleaves to form a free hydroxyl, amino, or sulfhydryl group, respectively. Examples of prodrugs include, but are not limited to, acetate, formate and benzoate derivatives of alcohol and amine functional groups in the compounds of formula (I); and the like. The term "therapeutically effective amount" of a compound of this invention means an amount effective to antagonize abnormal level of CRF or treat the symptoms of affective disorder, anxiety or depression in a host. Synthesis The pyrazinones and triazinones of this invention can be prepared by one of the general schemes outlined below (Scheme 1-6) . Compounds of the Formula (I) wherein Z = CH, Y = NR 4 , R 1 = halogen and R 2 = H can be prepared as shown in Scheme 1. Compounds wherein R 2 is a substituent other than H as defined in the broad scope of the invention can also be prepared as shown in Scheme 1 by using the corresponding R 2 COH substituted aldehydes or C1CHR 2 CN substituted haloacetonitriles . Scheme 1 1) H 2 NR : + NH 2 R 3 1) H 2 NR 3 MCN + CH 2 0 < ^ Base C1CH 2 CN 2) HY CN 2) HY III R'COCOR 1 IV V Wherein R = halogen Reaction of a cyanide salt with formaldehyde and the appropriate substituted amine afforded the corresponding aminoacetonitrile which was purified as the hydrochloride salt of Formula (III) . Alternatively the same compounds of Formula (III) can be synthesized by reaction of the amine H 2 NR 3 with a haloacetonitrile, such as chloroacetonitrile, in the presence of a base such as a tertiary amine or an inorganic base such as KC0 3 in an organic solvent and isolated as a salt of an inorganic acid by treatment with that acid. Amine salt of Formula (III) was treated ' with an oxalyl halide, R-'-COCOR 1 , such as oxalyl chloride or bromide to afford the dihalo compound Formula (IV) , as described in Vekemans, J.; Pollers- ieers, C. ; Hoornaert, G. J. Heterocyclic Chem. 20, 919, (1982). Compound Formula (IV) can be coupled with an aryl amine HNAr thermally, in the presence of a strong base such as NaH, KN(SiMe 3 ) , LiN(SiMe 3 ) or NaN(SiMe 3 ) 2 in an aprotic organic solvent, or under acid catalysis to give compounds of Formula (V) . Compounds of Formula (V) can be alkylated with an alkyl halide RX to afford compounds of Formula (I) . Compounds where R 1 = alkyl or substituted alkyl can be prepared according to Scheme 2. Scheme 2 IV VII 2 ) H 2 NAr VIII IX Reaction of the intermediate of Formula (IV) in Scheme 1, wherein R 1 = X = halogen in Scheme 2, with an alkyl or aryl thiol, HSR", in the presence of base such as NaH affords the adduct of Formula (VII) , which may then be treated with a trialkylaluminum as described in Hirota, K. ; Kitade, Y. ,- Kanbe, Y. ; Maki, Y. ; J " . Org . Chem. 57, 5268, (1992), in the presence of a palladium catalyst, such as Pd(PPh 3 ) C1 2 , to give compounds of Formula (VIII) . Condensation of compounds of Formula (VIII) with an aryl amine H 2 NAr under thermal, base, or acid catalyzed conditions gives compounds of Formula (IX) . Alternatively (VIII) may be oxidized to the corresponding sulfones with an oxidant such as K nθ 4 and then condensed with the arylamines of formula H 2 NAr to give (IX) . The use of appropriately substituted aluminum alkyls, or simple transformations of those substituted alkyls can give access to compounds of Formula (I) , where R 1 is a substituted alkyl; see Ratovelomanana, V. ;Linstrumelle, G.; Tet. Letters 52, 6001 (1984) and references cited therein. Compounds of the Formula (I) wherein Z = CH, Y = O or S(0) n and R 1 = halogen can be prepared as shown in Scheme Scheme 3 IV X XI Wherein R 1 = halogen XI XII n= 1,2 Reaction of the dihalo intermediate (IV) from Scheme 1 with a phenoxide or thiophenoxide, formed by treatment of the corresponding phenol or thiophenol with an appropriate base, such as NaH in an aprotic solvent, gives the adduct of Formula (X) or (XI) . Adduct (XI) may be further oxidized to the sulfoxide or sulfone of Formula (XII) , by treatment with the appropriate oxidant, such as a peroxide, NaI04 or KMn04. Compounds of Formula (I) where R 1 = OR, SR and S(0) n R and Z= CH can be introduced on compounds of Formula (V) by copper or copper salt-catalyzed coupling of the corresponding anions RO ~ and RS " with the pyrazinone bromide. Keegstra, M.A. ,- Peters, T.H.A. ; Brandsma, L.; Tetrahedron, 48, 3633 (1992) describes the addition of phenoxide anions by this method; alternatively, the same conditions can be used for the addition of thiophenoxide anions. Alternatively the same compounds can be synthesized by Scheme 4. Scheme 4 III XIII XIV + XVI XV XIX XX In Scheme 4, reaction of an aminoacetonitrile salt (III), described in Scheme 1, with an oxalyl halide ester (XIII) gives the corresponding amide (XIV) , which in turn can be converted to the corresponding imidate salt (XV) . This can be cyclized under treatment with a base, such as K 2 Cθ3 or Et3 to the pyrazinedione of Formula (XVI) . This can be converted to the corresponding halide (XIX) , using a halogenating agent such as POX3, oxalyl halide or SOX 2 . Alternatively, (XVI) can be converted to the corresponding mesylate, tosylate or triflate, by treatment with the corresponding mesyl, tosyl, or triflic anhydride. Subsequently, (XIX) can be coupled with an aniline to the corresponding adduct of Formula (XX) , under the conditions described in Scheme 1, or (XIX) can be coupled with a phenoxide or thiophenoxide as described in Scheme 3 to yield compounds of Formula (I) wherein Y = 0 or S(0) n - Compounds of Formula (I) wherein R 1 = substituted N and Z = CH can be introduced on compounds of Formula (XV) by reaction with an amine to form the corresponding amidate (XVII) according to Scheme 5. Subsequently, (XVII) can be cyclized, halogenated, and substituted with the appropriate aniline, phenoxide or thiophenoxide as described in Scheme 4 above. Compounds of Formula I wherein Z = CH and R 1 = COR 7 or C0 2 R 7 can be synthesized from compounds of Formula (VII) by coupling with the appropriate vinyl aluminum or boron reagent in the presence of a palladium catalyst, such as Pd(PPh 3 ) 2 Cl , and further transformations of the vinyl group, using methods known to one skilled in the art. Scheme 5 XV XVII XVIII XX 1 XXII The compounds of Formula (I) where Z = CH and R 1 or R 3 is a functional group not compatible with the procedures of Schemes 1-5 may be prepared from precursors where the interfering functionality of R 1 or R 3 is protected using methods known to one skilled in the art (see T.W. Green and P.G.M. Wuts, Protecting Groups in Organic Synthesis , Wiley, New York, 1991) ; or from precursors bearing R 1 or R 3 groups amenable to later conversion into the desired functionality using standard methods (see J. March, Advanced Organic Chemistry, Wiley, New York, 1992) . Triazinones of Formula (I) wherein Z = N and Y = NR 4 , 0 or S(0) n can be prepared by the synthetic route shown in Scheme 6. Condensation of a substituted hydrazine with acetamidines or imidates provides amidrazones of Formula (XXX) (Khrustalev, V. A., Zelenin, K. N. Zhurnal Organicheskoi Khimii, Vol. 15, No. 11, 1979, 2280) . Cyclization of (XXX) with oxalyl derivatives such as oxalyl chloride provides diones of Formula (XXXI) . Treatment of (XXXI) with chlorodehydrating agents such as thionyl chloride, oxalyl chloride or phosphorous oxychloride provides chlorotriazinones of Formula (XXXII) , which may be treated with phenols, thiophenols, anilines and their heterocyclic analogs under basic, acidic or thermal conditions to provide compounds of Formula (I) where Z = N and Y = 0, S or NH, respectively. In the preceding instance where Y = NH, alkylation of the nitrogen atom with e.g. alkyl iodides provides the related compounds of Formula (I) where Z = N and Y = NR . In the preceding instance where Y = S, oxidation with e.g. mCPBA provides the compounds of Formula (I) where Z = N and Y = S(O) and S(0)2- The compounds of Formula (I) where Z = N and R 1 or R 3 is a functional group not compatible with the procedures of Scheme 4 may be prepared from precursors such as amidrazones of Formula (XXX) or substituted hydrazines where the Scheme 6 R J 1 NH MeOH NH R 3 - N. + NH 2 R l NH 2 R J A NH 2 XXX XXX XXXI XXXII Ar interfering functionality of R 1 or R 3 is protected using methods known to one skilled in the art (see T.W. Green and P.G.M. Wuts, Protectingr Groups in Organic Synthesis, Wiley, New York, 1991) ; or from precursors bearing R 1 or R 3 groups amenable to later conversion into the desired functionality using standard methods (see J. March, Advanced Organic Chemistry, Wiley, New York, 1992) . Triazinones of Formula (I) wherein Z = N and Y = NR 4 , 0 or S(0) n can also be prepared by the synthetic route shown in Scheme 7 Scheme 7 xxxrv CH 2 C1 2 XXXV XXXVI XXXI XXXVII Reaction of ethyl oxalyl chloride with acylated hydrazines of Formula (XXXIV) provides the ethyl oxalyl acylhydrazine derviatives of Formula (XXXV) . Compounds of Formula (XXXIV) may be arrived at via condensation of an appropriate ketone or aldehyde with an acylated hydrazide to give acylated hydrazones which may then be reduced under catalytic hydrogenation conditions or by other reducing agents to give the compounds of Formula (XXXIV) . The abovementioned acylated hydrazones may also be produced by acylation of a hydrazone made from hydrazine and an appropriate ketone or aldehyde using methods known to one skilled in the art of organic synthesis. Alternatively, compounds of Formula (XXXIV) may also be produced by acylation of an appropriate hydrazine using methods known to one skilled in the art of organic synthesis. The ethyl esters of compound (XXXV) may then be converted to the primary amide derivatives of Formula (XXXVI) by treatment with an ammonia source such as ammonium hydroxide. Cyclization of (XXXVI) to produce the diones of Formula (XXXI) may be achieved by treatment with, for example, iodotrimethylsilane (TMSI) or POCI 3 , or by heating in the presence of a Lewis acid such as ZnCl . The oxo group in the 5 position of the 1, 2 , 4-triazin-5, 6-diones of Formula (XXXI) may then be converted to a leaving group using reagents such as trifluoromethanesulfonic anhydride under basic conditions to yield compounds of Formula (XXXVII) which may then be treated with phenols, thiophenols, anilines and their heterocyclic analogs under basic conditions to provide compounds of Formula (I) Additional 1, 2 , 4-triazinone syntheses are disclosed in the literature (A. R. Katritzky and C. W. Rees, Comprehensive Heterocyclic Chemistry, Pergamon Press, New York, Vol. 3, 1984, p. 385) and can be prepared by one skilled in the art . Intermediates, for example ArYH, HNAr, HOAr or HSAr, in the synthesis of compounds of Formula (I) in Schemes 1-6 may be prepared using standard methods known to one skilled in the art (see, D. Barton and W. D. Ollis, Comprehensive Organic Chemistry, Pergamon Press, New York, Vol. 1-6, 1979; A. R. Katritzky and C. W. Rees, Comprehensive Heterocyclic Chemistry, Pergamon Press, New York, Vol. 1-8, 1984; B. Trost and I. Fleming, Comprehensive Organic Synthesis, Pergamon Press, New York, Vol. 1-9, 1991; and DuPont Merck PCT application WO95/10506) . All of the aforementioned references are hereby incorporated by reference . Example 1 3 - [ [ 2 -Bromo-4 - ( 1 -me hy let hyl ) phenyl ] amino ] - 5 - chloro- 1 - ( 1 -ethylpropyl ) - 2 ( IH ) -pyraz inone Part A: Hydrogen chloride ( 12M, aq . , 3 . 8 mL) , methanol ( 33 mL) , water ( 30 mL) , potassium cyanide (3 g) , 1-ethylpropylamine ( 4 g) , and formaldehyde (37% w/v, 3 . 7 mL) were stirred 18 hours at room temperature. Water (200 mL) was added, and the mixture was extracted with 2 x 200 mL methylene chloride, which was dried over MgS04 and concentrated to a light oil (5.57 g) . The oil was dissolved in ether and IN HCl was added. The precipitate was collected on paper and dried to give N- (1-ethylpropyl) - aminoacetonitrile hydrochloride as an off-white solid (6.70g) . Part B: The product from part A (2 g) , chloroform (20 mL) , and oxalyl chloride (4.68 g) were heated at reflux for 12 hours. The reaction was concentrated to remove excess oxalyl chloride and solvent, and the crude product was chromatographed on silica gel using ethyl acetate/hexane (1:4) as eluent to afford 3 , 5-dichloro-l- (1- ethylpropyl) -2 (IH) -pyrazinone as a white solid (2.09 g) . Part C: The product from part B (0.68 g) and 2- bromo-4-isopropylaniline (1.24g) were heated at 140°C for 5 hours. After cooling, methylene chloride (20 mL)was added, filtered, and concentrated. The crude product was chromatographed on silica gel using ethyl acetate/hexane (1:9) as eluent to afford the title compound. 639 mg. mp 118.5 - 119.5°C. Elemental analysis: calcd. for Cl8H23N30BrCl: C, 52.38; H, 5.626; N, 10.18; Br, 19.36; Cl, 8.599. Found: C, 52.62; H, 5.43; N, 10.13; Br, 19.53; Cl, 8.97. Example 2 3- [ [2-Bromo-4- ( 1-methylethyl) phenyl] ethylamino] -5- chloro-1- (1-ethylpropyl) -2 (IH) -pyrazinone The product from Example 1 (198 mg) , N,N-dimethyl- formamide (5 mL) , and sodium hydride (60% in oil, 96 mg) were stirred at room temperature 20 minutes. Iodoethane (112 mg) was added and the reaction was stirred overnight at room temperature and quenched with water (10 mL) and saturated sodium chloride (aq. , 10 mL) . The mixture was extracted with methylene chloride which was dried and concentrated. The crude product was chromatographed on silica gel using ethyl acetate/hexane (1:19) as eluent to afford the title compound (125 mg) . CI-HRMS calcd. for C20H28N3OClBr (M+H)+: 440.110427. Found: 440.107480. Example 3 3- [ (2, -Dibromophenyl) amino] -5-chloro-l- (1- ethylpropyl) -2 (IH) -pyrazinone 2, 4-Dibromoaniline (500 mg) , toluene (8 mL) , and sodium hydride (60% in oil, 398 mg) were stirred for 10 minutes at room temperature and then 3 , 5-dichloro-l- (1- ethylpropyl) -2 (IH) -pyrazinone (468 mg, Example 1, part B) was added. The reaction was heated at reflux 3 hours, cooled, and quenched with water (50 mL) . The mixture was extracted with ethyl acetate (100 mL) , which was washed with brine, then dried and concentrated. The crude product was chromatographed on silica gel using ethyl acetate/hexane (1:19) affording 400 mg of material, which was crystallized from ether/hexane to give the title compound (240 mg) . Elemental analysis: calcd. for Cl5Hl6N30ClBr2 : C, 40.07; H, 3.597; N, 9.356; Cl, 7.895; Br, 35.55. Found: C, 40.41; H, 3.49; N, 9.34; Cl, 8.27; Br, 35.71. Example 4 3- [ (2, 4-Dibromophβnyl) ethylamino] -5-chloro-l- (1- ethylpropyl) -2 ( IH) -pyrazinone The title compound was prepared in a manner similar to the product of Example 2. Elemental analysis calcd. for Ci7H20 3OClBr2: C42.75; H,4.22; N, 8.807. Found: C, 42.82; H, 4.14; N, 8.67. Example 5 3- [ (2, 4, 6-Trimethylphenyl) amino] -5-chloro-l- (1- ethylpropyl) -2 (IH) -pyrazinone The title compound was prepared in a manner .similar to the product of Example 3. Elemental analysis calcd. for C18H24N3OCI: C, 64.76; H, 7.256; N, 12.59. Found: C, 64.69; H, 7.03; N, 12.55. Example 6 3- [ (2, 4, 6-Trimethylphenyl) ethylamino] -5-chloro-l- ( 1-ethylpropyl) -2 (IH) -pyrazinone The title compound was prepared in a manner similar to the product of Example 2. Elemental analysis calcd. for C20H28N3OC1: C, 66.37; H, 7.808; N, 11.61. Found: C, 66.50; H, 7.69; N, 11.51. Example 7 (+/-)-3-[(2,4, 6-Trimethylphenyl) amino] -5-chloro-l- [1- (methoxymethyl) propyl] -2 (IH) -pyrazinone The title compound was prepared in a manner similar to the product of Example 3. Elemental analysis calcd. for CI8H24N3O2CI: C, 61.80; H, 6.91; N, 12.01; Cl, 10.13. Found: C, 61.69; H, 7.00; N, 11.93; Cl, 9.87. Example 8 3- [ (2-Bromo-4, 6-dimethoxyphenyl) amino] -5-chloro-l- ( 1-ethylpropyl ) -2 ( IH) -pyrazinone The title compound was prepared in a manner similar to the product of Example 3. Elemental analysis calcd. for Ci7H2lN3θ3BrCl: C, 47.40; H, 4.91; N, 9.765. Found: C, 47.06; H, 4.61; N, 9.56. Example 9 3- [ (2-Cyano-4, 6-dimethylphenyl) amino] -5-chloro-l- ( 1-ethylpropyl) -2 (IH) -pyrazinone Part A: 3- [ (2-Iodo-4 , 6-dimethylphenyl) amino] -5- chloro-1- (1-ethylpropyl) -2 (IH) -pyrazinone was prepared in a manner similar to Example 3. Part B: The product from part A (460 mg) , N,N- dimethylformamide (8 mL) , cuprous cyanide (97 mg) , and sodium cyanide were heated at 120°C for 18 hours and then at 130°C for 3 hours. After cooling, ethyl acetate (100 mL) was added to the reaction which was then washed with water (50 mL) and brine (50 mL) , dried, and concentrated. The crude product was chromatographed on silica gel using ethyl acetate/hexane (1:4) as eluent. The product was then crystallized from methylene chloride/hexane to afford the title compound (235 mg) . Elemental analysis calcd. for CI8H21N4OCI: C, 62.69; H, 6.148; N, 16.25; Cl, 10.28. Found: C, 62.29; H, 6.27; N, 15.99; Cl, 10.20. Example 10 (+/-)-3-[ (2-Bromo-4, 6-dimethoxyphenyl) mino] -5- chloro-1- [1- (methoxymethyl) propyl] -2 (IH) -pyrazinone The title compound was prepared in a manner similar to the product of Example 3. Elemental analysis calcd. for Ci7H2lN3θ4BrCl: C, 45.71; H, 4.748; N, 9.416. Found: C, 45.86; H, 4.43; N, 9.26. Example 12 (+/-) -3- [ (2-Iodo-4, 6-dimethylphenyl) amino] -5- chloro-1- [1- (methoxymethyl) propyl] -2 (IH) -pyrazinone Part A: Chloroacetonitrile (3.2 mL) , 2-amino-l- methoxybutane (10.32 g) , and deuterochloroform (50mL) were stirred and heated at reflux for 48 h. Methylene chloride (100 mL) and sodium hydroxide (aq., IN, 100 mL) were added to the reaction, the layers separated, and the organic layer concentrated to an oil (3.4 g) . The oil was dissolved in ether (100 mL) and HCl/ether (IN, 100 mL) was added. The precipitate was collected on paper affording N- [ (1-methoxymethyl) propyl]aminoacetonitrile hydrochloride (6.86 g) . Part B: The title compound was prepared in a manner similar to the product of Example 3. Elemental analysis calcd. for C17H21N3O2CH : C, 44.22; H, 4.58; N, 9.10. Found: C, 44.26; H, 4.60; N, 9.83. Example 15 (+/-)-3-[ (4-Bromo-2, 6-dimethylphenyl) amino] -5- chloro-1- [1- (methoxymethyl) propyl] -2 (IH) -pyrazinone To (+/-) -3 , 5-dichloro-l- [1- (methoxymethyl) propyl] - 2 (IH) -pyrazinone (300 mg) and 4-bromo-2 , 6-dimethylaniline (238 mg) in THF (anhydrous, 9.4 mL) at 0°C was added sodium bis (trimethylsilyl) amide (1.0 M/THF, 2.6 mL) . The mixture was stirred at 0°C for 10 minutes. Ethyl acetate (lOOmL) was added and washed with water (25 mL) and brine (25 mL) . The organic layer was dried over MgSθ4 and concentrated and the crude product was chromatographed on silica gel using ethyl acetate/hexane (1:4) as eluent. The product was then crystallized from ethyl acetate/hexane to afford the title compound (419 mg) . Elemental analysis calcd. for Ci7H2lN3θ2BrCl: C, 49.23; H, 5.10; N, 10.13. Found: C, 49.33; H, 5.05; N, 10.09. Example 16 (+/-) -3- [ (4-Acetyl-2, 6-dimethylphenyl) amino] -5- chloro-1- [1- (methoxymethyl) propyl] -2 (IH) -pyrazinone To the product of Example 15 (250 mg) , bis (triphenylphosphine) palladium (II) chloride (11 mg) , and tetrakis (triphenylphosphine)palladium(O) (17 mg) in a dry flask under nitrogen was added toluene (1.5 mL) and 1- ethoxyvinyl tributyl tin (260 mg) . The reaction was heated at reflux 18 hours, and then concentrated in vacuo . The residue was taken up in ether (15 mL) and saturated aqueous potassium fluoride (15 mL) , and filtered. The layers were separated, and the ether layer was stirred with IN HCl (aq. , 15 mL) . The layers were separated and the ether layer was dried over MgSθ4 and concentrated. The crude product was chromatographed on silica gel using ethyl acetate/hexane (3:7) as eluent to afford the title compound (90 mg) . Elemental analysis calcd. for C19H24N3O3CI : C, 60.39; H, 6.40; N, 11.12. Found: C, 60.51; H, 6.31; N, 11.00. Example 16a (+/-)-3-[ (4-Acetyl-2-methoxy-6-methylphenyl) amino] - 5-chloro-l- [1- (methoxymethyl) propyl] -2 (IH) - pyrazinone The title compound was prepared in a manner similar to the product of Example 16. Elemental analysis calcd. for C19H24N3O4CI: C, 57.94; H, 6.14; N, 10.67. Found: C, 57.70; H, 5.98; N, 10.41. Example 20 (+/-)-3-[ (4-Chloro-2-iodo-6-methylphβnyl) amino] -5- chloro-1- [1- (methoxymethyl ) ropyl] -2 ( IH) -pyrazinone The title compound was prepared in a manner similar to the product of Example 3. Elemental analysis calcd. for C16H18N3O2CI2I: C, 39.86; H, 3.76; N, 8.725. Found: C, 40.00; H, 3.69; N, 8.64. Example 21 3- [ (2,4, 6 -Trimethylphenyl) amino] -5-chloro-l- [1- ( methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone Part A: To serinol (9.90 g) in DMF (200 mL) was added triethyl amine (14.6 mL) and then chlorotriphenylmethane (24.3 g) . The reaction mixture was stirred at room temperature for 18 hours. Toluene (800 mL) was added and washed with water (500 mL and 250 mL) and brine (250 mL) , and then dried over K2CO3 and concentrated to dryness . The product was crytallized from benzene/hexane (1:1) to afford product (14.57 g) . Part B: The product from part A (14.57 g) , sodium hydroxide (17.5 g) , and iodomethane (8.8 mL) were stirred overnight in DMSO (220 mL) at room temperature. Water (500 mL) was added and extracted with ethyl acetate (3 X 250 mL) . The extracts were washed with water (2 X 250 mL) and brine (200 mL) , dried over K2CO3, and concentrated to give product (14.46 g) . Part C: The product from part B (14.46 g) and hydrogen chloride (1M/Et20, 84 mL) were stirred in methanol (300 mL) at room temperature for 6 hours. The solution was washed with hexane (3 X 300 mL) , concentrated, and co- evaporated with ethanol affording 2-amino-l, 3-methoxypropane (5.69 g) . Part D: The title compound was prepared in a manner similar the product of Example 3. Elemental analysis calcd. for C18H24N3O3CI: C, 59.09; H, 6.61; N, 11.49. Found: C, 59.27; H, 6.53; N, 11.47. Example 30a (+/- ) -3- [ (2-Chloro-4, 6-dimethylphenyl) amino] -5- methyl-1- [1- (methoxymethyl) propyl] -2 (IH) -pyrazinone The title compound was prepared in a manner similar to the product of Example 84. Elemental analysis calcd. for C18H24N302C1: C, 61.80; H, 6.91; N, 12.01. Found: C, 61.70; H, 6.94; N, 11.56. Example 36 3 - [ ( 2 , 4 , 6 -Trimethylphenyl ) amino ] -5 -chloro- l - [ 1- (methoxymethyl ) -3 -methoxypropyl ] - 2 ( IH) -pyrazinone The title compound was prepared in a manner similar to the product of Example 15 . Elemental analysis calcd . for C19H26N3O3CI: C, 60.07; H, 6.908; N, 11.06. Found: C, 60.22; H, 7.16; N, 10.92. Example 36a 3- [ (4-Bromo-2-methoxy-6-methylphenyl) amino] -5- chloro-1- [1- (methoxymethyl ) -3-methoxypropyl] -2 (IH) ■ pyrazinone The title compound was prepared in a manner similar to the product of Example 15. Elemental analysis calcd. for Ci8H23N3θ4ClBr: C, 46.92; H, 5.03; N, 9.129. Found: C, 47.29; H, 5.03; N, 8.98. Example 45a 3- [ (2-Bromo-6-f louro-4-methylphenyl) amino] -5- chloro-1- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) pyrazinone The title compound was prepared in a manner similar to the product of Example 15. Elemental analysis calcd. for Ci6Hi8N3θ3FClBr: C, 44.21; H, 4.17; N, 9.67. Found: C, 44.35; H, 4.25; N, 9.41. Example 46a 3- [ (2-Chloro-4-methoxy-6-mβthylphenyl) amino] -5- chloro-1- [1- (methoxymethyl ) -2-methoxyethyl] -2 ( IH) pyrazinone The title compound was prepared in a manner similar to the product of Example 15. Elemental analysis calcd. for C17H20N3O4CI2: C, 50.89; H, 5.02; N, 10.47. Found: C, 50.72; H, 5.33; N, 10.37. Example 49 3- [ (4-Bromo-2, 6-dimethylphenyl) amino] -5-chloro-l- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) - pyrazinone The title compound was prepared in a manner similar to the product of Example 15. Elemental analysis calcd. for Ci8H23N3θ3ClBr: C, 48.61; H, 5.21; N, 9.457. Found: C, 48.59; H, 5.32; N, 9.45. Example 53 3- [ (4-Bromo-2, 6-dimethylphenyl) amino] -5-chloro-l- [1- (methoxymethyl ) -2-methoxyethyl] -2 ( IH) -pyrazinone The title compound was prepared in a manner similar to the product of Example 15. Elemental analysis calcd. for Cl7H2lN3θ3ClBr: C, 47.40; H, 4.91; N, 9.765. Found: C, 47.52; H, 4.99; N, 9.72. Example 54 3- [ (2-Chloro-4, 6-dimethylphenyl) amino] -5-chloro-l- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone The title compound was prepared in a manner similar to the product of Example 15. Elemental analysis calcd. for C17H21 3O3CI2: C, 52.86; H, 5.489; N, 10.88. Found: C, 52.89; H, 5.44; N, 10.72. Example 77 (+/-)-3-[(2, 6 -Dimethyl -4 -thiomethylphenyl) amino] -5- chloro-1- [1- (methoxymethyl) propyl] -2 (IH) -pyrazinone The title compound was prepared in a manner similar to the product of Example 15. Elemental analysis calcd. for CI8H24N3O2CIS: C, 56.62; H, 6.33; N, 11.00; S, 8.405. Found: C, 56.66; H, 6.19; N, 10.89; S, 8.45. Example 79 (+/-) -3- [ (2-Chloro-4, 6-dimethylphenyl) amino] -5- chloro-1- [1- (methoxymethyl) propyl] -2 (IH) -pyrazinone The title compound was prepared in a manner similar to the product of Example 15. Elemental analysis calcd. for C17H21N3O2CI2: C 55.14; H, 5.726; N, 11.35. Found: C, 55.27; H, 5.70; N, 11.25. Example 80 (+/-) -3- [ (4-Bromo-6-methoxy-2-methylphenyl) amino] - 5-chloro-l- [1- (methoxymethyl) propyl] -2 (IH) - pyrazinone The title compound was prepared in a manner similar to the product of Example 15. Elemental analysis calcd. for Ci7H2lN303BrCl: C, 47.40; H, 4.91; N, 9.765. Found: C, 47.91; H, 4.95; N, 9.74. Example 81 3- [ (2, 6 -Dime thyl-4 -thiomethylphenyl) amino] -5- chloro-1- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) - pyrazinone The title compound was prepared in a manner similar to the product of Example 15. Elemental analysis calcd. for C18H24N3O3CIS: C, 54.33; H, 6.08; N, 10.56; S, 8.06. Found: C, 54.48; H, 6.01; N, 10.46; S, 7.86. Example 83 3- [ (4-Bromo-2-methoxy-6-methylphenyl ) amino] -5- chloro-1- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) - pyrazinone The title compound was prepared in a manner similar to the product of Example 15. Elemental analysis calcd. for Cl7H2lN3θ4ClBr: C, 45.71; H, 4.748; N, 9.416. Found: C, 45.80; H, 4.70; N, 9.39. Example 84 3- [(2,4, 6-Trimethylphenyl) amino] -1- (1-ethylpropyl) - 5-methyl-2 (IH) -pyrazinone Part A: N- (1-ethylpropyl) aminoacetonitrile hydrochloride (1.41 g) and oxalyl bromide (2.0 M/CH2CI2, 13 mL) were heated at reflux for 18 hours. The reaction was concentrated to remove excess oxalyl bromide and solvent, and the crude product was chromatographed on silica gel using ethyl acetate/hexane (1:4) as eluent to afford 3,5- dibromo-1- (1-ethylpropyl) -2 (IH) -pyrazinone as a white solid (1.19 g) . Part B: The product from part A (133 mg) and sodium thiomethoxide (29 mg) were combined in THF (1.5 mL) and stirred at 25 °C 4 hours. More sodium thiomethoxide (29 rag) was added and the reaction was stirred for 2 hours more at room temperature. Water (20 mL) was added and extracted with CH2CI2 (2 X 20 mL) . The organic layers were combined, dried over MgS04, and concentrated. The crude product was chromatographed on silica gel using ethyl acetate/hexanes (1:4) as eluent to afford 5-bromo-1- (1-ethylpropyl) -3- thiomethyl-2 (IH) -pyrazinone (78 mg) . Part C: The product from part B (200 mg) and Pd(PPh 3 ) 2 Cl 2 (40 mg) were combined in dry THF (6 mL) under inert atmosphere (N 2 ) . To that a 2M solution AlMe 3 in hexanes (0.5 mL) was added and the reaction was heated at reflux for one hour. The excess AlMe 3 was quenched with water at 0 °C and the mixture was partitioned between ethyl acetate (50 mL) and water (30 mL) . The water was separated and extracted with ethyl acetate (50 mL) , and the combined EtOAc extracts were washed with brine, dried (MgS0 4 ) and stripped in vacuo. The crude product was chromatographed on silica gel using ethyl acetate/hexanes as eluent (1:9) to give 1- (1-ethylpropyl) -5-methyl-3-thiomethyl-2 (IH) - pyrazinone (100 mg) . Part D: The product from part B (50 mg) and 2,4,6- trimethylaniline (40 mg) were combined in dry THF (2 mL) under inert atmosphere (N ) , and cooled to 0 °C . To that a 1M solution NaN(SiMe3) in THF (0.5 mL) was added dropwise and the reaction was stirred at 0 °C for 20 min. Then an additional NaN(SiMe3) in THF (0.3 mL) was added and the reaction was stirred at 0 °C for 30 min and at 25 °C for one hour. Then it was quenched with water (30 mL) and extracted with ethyl acetate (80 mL) . The ethyl acetate was washed with brine, dried (MgS0 ) and stripped in vacuo . The crude product was chromatographed on silica gel using ethyl acetate/hexanes as eluent (1:9) to give 3- [(2,4,6- trimethylpheny1 ) amino] -1- (1-ethylpropyl) -5-methyl-2 (IH) - pyrazinone (40 mg) . mp. 109 "C. Example 84a 3- t (2-Chloro-4, 6-dimethylphenyl) amino] -1- ( 1- ethylpropyl) -5-methyl-2 (IH) -pyrazinone The title compound was prepared in a manner similar to the product of Example 84. Elemental analysis calcd. for C18H24N3OCI: C, 64.76; H, 7.256; N, 12.59. Found: C, 65.12; H, 7.28; N, 12.33. Example 84b 3- [ (2-Chloro-4-methoxy-6-methylphenyl) amino] -1- (1- ethylpropyl ) -5-methyl-2 ( IH) -pyrazinone The title compound was prepared in a manner similar to the product of Example 84. Elemental analysis calcd. for C18H24N3O2CI: C, 61.80; H, 6.91; N, 12.01. Found: C, 61.72; H, 6.96; N, 11.83. Example 84c 3- [ (2, 4, 6-Trimethylphenyl) amino] -1- (1-ethylpropyl) - 5-ethyl-2 (IH) -pyrazinone Part A: 5-bromo-l- (1-ethylpropyl) -3 -thiomethyl- 2 (IH) -pyrazinone was prepared in a manner similar to Example 84, parts A and B. Part B: To the product of part A (2.14 g) and bis (triphenylphosphine) palladium (II) chloride (258 mg) in anhydrous THF (60 mL) under inert atmosphere was added triethyl aluminum (1 M/THF, 14.7 mL) . The reaction was heated at reflux 3 hours and then cooled and quenched with water. Ethyl Acetate (200 mL) was added and washed with water and saturated aqueous sodium chloride. The ethyl acetate was dried over MgSθ4 and concentrated in vacuo. The crude product was chromatographed on silica gel using ethyl acetate/hexane (3:17) as eluent to afford 5-ethyl-l- ( 1-ethylpropyl) -3-thiomethyl-2 (IH) -pyrazinone (809 mg) . Part C: The title compound was prepared in a manner similar to the product of Example 84 using the procuct from part B. Elemental analysis calcd. for C20H29N3O: C, 73.36; H, 8.936; N, 12.83. Found: C, 73.01; H, 8.55; N, 12.69. Example 84d 3- [ (2-Chloro-4, 6-dimethylphenyl) amino] -1- (1- ethylpropyl) -5-ethyl-2 (IH) -pyrazinone The title compound was prepared in a manner similar to the product of Example 84c. Elemental analysis calcd. for 19H26 30C1: C, 65.60; H, 7.53; N, 12.08. Found: C, 65.53; H, 7.33; N, 11.92. Example 85 3-[(2,4, 6 -Trimethylphenyl) amino] -5-bromo-l- (1- ethylpropyl) -2 ( IH) -pyrazinone Part A: N- (1-ethylpropyl) -aminoacetonitrile hydrochloride (1.41 g) and oxalyl bromide (2.0 M, CH2C12, 13 mL) were heated at reflux for 18 hours. The reaction was concentrated to remove excess oxalyl bromide and solvent, and the crude product was chromatographed on silica gel using ethyl acetate/hexane (1:4) as eluent to afford 3, 5-dibromo-l- (1-ethylpropyl) -2 (IH) -pyrazinone as a white solid (1.19 g) . Part B: Using the product of part A, the title compound was prepared in a manner similar to the product of Example 3. MS m/z 378, (m+H) + , 100%. Example 204 5- [ (2,4, 6-Trimethylphenyl) amino] -3 -methyl-1- (1- ethylpropyl) -1, 2, 4-triazine-6 (IH) -one Part A: 3-Pentanone (18.56 g, 0.215 mol), acetic hydrazide (14.8 g, 0.2 mol), and 200mL of absolute ethanol were placed in a 500mL flask. The reaction mixture was reluxed for 18hr and then evaporated to dryness to afford the desired hydrazone of suitable purity. The hydrazone was then dissolved in 200mL of glacial acetic acid containing 1.0 g of Pt0 2 and hydrogenated at 50 psi hydrogen pressure for 14 hr. The mixture was decanted from the catalyst and evaporated to dryness to afford 23.9 g of a colorless oil (83% yield for the two steps) . Part B: The l-acetyl-2- (1-ethylpropyl) hydrazine product from Part A (23.9 g, 0.166 mol) was dissolved in CHC1 (200mL) and to the stirring solution was added triethylamine (27.9 mL, 0.2 mol) and ethyl oxalyl chloride (19 mL, 0.17 mol) . After stirring at room temperature for 3 hr, the reaction mixture was poured into water and the organic layer was separated, dried (Na 2 Sθ 4 ) , filtered and evaporated in vacuo. To the resultant oil was added ammonium hydroxide (250mL) , THF (lOOmL) , and ethanol (50mL) . The flask containing the mixture was sealed with a rubber septum and stirred for 18 hr at room temperature. The mixture was then concentrated in vacuo until the reduced volume of solvent remaining was approximately lOOmL, and a white precipitate had formed. The flask was then placed in the refrigerator for 1 hr. The precipitate was collected by vacuum filtration and washed with small volumes of cold water. 26.3 g of a white solid was collected (73.% yield) . ! H NMR (300MHz, CDC1 3 ) : 6 7.78 (s, IH) ; 6.74 (br s, IH) ; 5.6 (br s, IH) ; 4.25 (m, IH) ; 2.04 (s, IH) ; 1.5 (m, 4H) ; 0.95 (t, 6H, J = 7.3 Hz) . Part Ci The 1-oxamyl-l- (3-pentyl) -2-acetylhydrazine product from Part B (2 g, 9.3 mmol) was suspended in chloroform (50mL) and 2 mL of iodotrimethylsilane was added dropwise. The mixture was allowed to stir at room temperature for 12 hr. The reaction mixture was then partitioned between CHC1 and IN NaOH. The aqueous layer was separated and made acidic by addition of cone. HCl and then extracted with CH 2 C1 2 . This organic layer was dried (Na 2 Sθ 4 ) , filtered and evaporated in vacuo to yield 1.2 g of an off-white solid of suitable purity (65% yield) . -'-H NMR (300MHz, CDCI 3 ) : δ 7.85 (br s, IH) ; 4.61 (m, IH) ; 2.35 (s, 3H) ; 1.73 (m, 4H) ; 0.83 (t, 6H, J = 7.3 Hz). Part Di To a solution of the triazine dione product from above (198 mg, 1 mmol) in CH 2 C1 2 (5 mL) was added trifluoromethanesulfonic anhydride (0.19 mL, 1.1 mmol) and 2 , 4, 6-collidine (0.15 mL, 1.1 mmol). The resulting reaction mixture was stirred at room temperature for 30 min. , then 2, 4, 6-trimethylaniline (162 mg, 1.2 mmol) in 5 mL of THF was added followed by addition of 2, 4, 6-collidine (0.15 mL, 1.1 mmol) . The resulting reaction mixture was stirred at room temperature for 1 hr, at which time TLC showed complete reaction. The reaction mixture was partitioned between water and CH 2 Cl 2 . The organic layer was dried (Na Sθ 4 ) , filtered and evaporated in vacuo . The residue was purified by column chromatography on silica gel using EtOAc / hexane (1:9) to afford 260 mg of the title compound (83% yield) . mp = 133 - 135°C. 1 H NMR (300MHz, CDCI 3 ): δ 7.89 (br s, IH) ; 6.94 (s, 2H) ; 4.72 (m, IH) ; 2.31 (s, 3H) ; 2.19 (s, 9H) ; 1.9 - 1.7 (m, 4H) ; 0.85 (t, 6H, J = 7.32 Hz). Mass Spec. (NH 3 - CI) : Calc. (M+H)+ = 315, Obs . (M+H)+ = 315. Example 703 (+/-) -5-Chloro-l- [1- (methoxymethyl) propyl] -3- (2,4, 6-trimethylphenoxy) -2 (IH) -pyrazinone Part Ax (+/-)-3,5-dichloro-l-[l- (methoxymethyl ) propyl] -2 (IH) -pyrazinone was prepared in a manner similar to Example 12, part A, and Example 1, part B. Part Bt 2,4, 6-Trimethylphenol (59 mg) and potassium t-butoxide (48 mg) were added to pyridine (2 mL) at 0°C. The mixture was warmed to ambient temperature and (+/-)-3,5- dichloro-1- [1- (methoxymethyl) propyl] -2 (IH) -pyrazinone (98 mg) and copper (I) iodide (19 mg) were added. The reaction mixture was stirred at ambient temperature for three hours and then heated at reflux for three hours and then cooled to 0°C. Ethyl acetate (50 mL) and saturated ammonium chloride (50 mL) were added and the mixture was stirred overnight at ambient temperature. The layers were separated, and the organic layer was washed with 1M ammonium hydroxide (2 x 50 mL) , IN sodium hydroxide (2 x 50mL) , IN hydrochloric acid (2 x 50mL) , and saturated sodium chloride (50 mL) . The ethyl acetate was dried over MgSθ4 and concentrated in vacuo . The crude product was chromatographed on silica gel using ethyl acetate/hexane (1:4) as eluent to afford the title compound (66 mg) . mp = 116°C. Elemental analysis calcd. for CI8H23N2O3CI: C, 61.62; H, 6.618; N, 7.98. Found: C, 61.45; H, 6.44; N, 7.77. Various analogs synthesized using Schemes 1, 2 and 3 are listed in Table 1. Table 1 Ex No Rl R3 Y λr mp/°C 1 Cl Et 2 CH NH 2-Br-4-iPr-phenyl 118.5 2 Cl Et CH NEt 2-Br-4-iPr-phenyl MS = 440 3 Cl Et 2 CH NH 2, 4 -Br 2 -phenyl 155.5 4 Cl Et 2 CH NEt 2 , 4 -Br 2 -phenyl 88.1 5 Cl Et CH NH 2,4, 6 -Me3 -phenyl 180.8 6 Cl Et 2 CH NEt 2,4, 6-Me3~phenyl 93.8 7 Cl MeOCH (Et)CH NH 2 , 4 , 6-Me3-phenyl 153.8 8 Cl Et CH NH 2-Br-4,6-(MeO) 2 - 181.3 phenyl 9 Cl Et CH NH 2-CN-4,6-Me -phenyl 174.0 10 Cl MeθCH 2 (Et)CH NH 2-Br-4,6- (MeO) 2 - 175.8 phenyl 11 Cl MeθCH 2 (Et)CH NH 2-Cl-4,6-(MeO) 2 - phenyl 12 Cl MeOCH 2 {Et)CH NH 2-1-4 , 6-Me 2 -phenyl 109.4 13 Cl MeOCH 2 (Et)CH NH 2-CN-4 , 6-Me -phenyl 14 Cl MeOCH (Et) CH NH 2-Br-4, 6-Me 2 -phenyl 15 Cl MeOCH (Et)CH NH 4-Br-2, 6-Me -phenyl 152.8 16 Cl MeOCH 2 (Et)CH NH 4-MeCO-2 , 6 -Me 2 -phenyl 127.1 16a Cl MeOCH (Et)CH NH 4 -MeCO- 2 -OMe- 6 -Me- 179.8 phenyl 7 Cl MeθCH 2 (Et)CH NH 2-MeC0-4, 6 -Me -phenyl 8 Cl MeθCH 2 (Et)CH NH 4, 6-Me -2-SMe-phenyl Cl MeOCH 2 (Et)CH NH 4, 6-Me 2 -2-S0 Me-phenyl Cl MeOCH 2 (Et)CH NH 4-Cl-2-I-6-Me-phertyl 121.8 Cl (MeOCH 2 ) 2 H NH 2,4, 6-Me3-phenyl 127.2 Cl phenyl NH 2,4, 6-Me3-phenyl CN MeθCH (Et)CH NH 2,4, 6-Me3-phenyl CONH 2 MeOCH 2 (Et)CH NH 2,4, 6-Me 3 -phenyl COOH MeOCH 2 (Et)CH NH 2,4,6- e3-phenyl CHO MeOCH (Et)CH NH 2,4, 6-Me 3 -phenyl CH OH MeOCH 2 (Et)CH NH 2,4, 6-Me3 -phenyl CH3 MeOCH 2 (Et)CH NH 2 , 4-Br 2 -phenyl CH 3 MeOCH 2 (Et)CH NH 2-Br-4-iPr-phenyl CH3 MeOCH (Et ) CH NH 2,4, 6-Me3-phenyl a CH 3 MeOCH 2 (Et)CH NH 2-C1-4 , 6-Me2-phenyl 117.9 CH3 {MeOCH 2 ) 2 CH NH 2,4, 6-Me3-phenyl CH 3 (MeOCH ) 2 CH NH 2 , 4-Cl 2 -6-Me-phenyl Cl (MeOCH ) CH NH 2, 4-Cl 2 -6-Me-phenyl Cl (MeOCH 2 ) 2 CH NH 2, 4-Br -6-Me-phenyl CH3 MeOC 2 H4 (MeOCH 2 ) CH NH 2,4, 6-Me3-phenyl Cl MeOC 2 H4 (MeθCH 2 ) CH NH 2,4, 6-Me3-phenyl 120.0 a Cl MeOC H4 (MeOCH 2 ) CH NH 4-Br-2-OMe-6-Me- 130.9 phenyl Cl (MeOC 2 H4) 2 CH NH 2,4, 6-Me3-phenyl Cl MeOCH 2 (Et ) CH NH 2 , 4-Me 2 -6-MeO-phenyl Cl MeOC H4 (MeOCH )CH NH 2, 4-Me 2 -6-MeO-phenyl CH3 MeOC H4 (MeOCH 2 ) CH NH 2 , 4-Me 2 -6-MeO-phenyl CH 3 MeOC H4 (MeOCH 2 ) CH NH 4-Br-2 , 6-Me 2 -phenyl CH3 MeOC H4 (MeOCH 2 )CH NH 2-C1-4, 6-Me 2 -phenyl CH 3 MeθC 2 H4 (MeOCH ) CH NH 2,4-Me -6-MeOCH 2 - phenyl CH3 (MeOCH ) 2 CH NH 2, 4-Me 2 -6-MeO-phenyl CH 3 (MeOCH 2 ) CH NH 4-Br-2 , 6-Me -phenyl a CH3 (MeOCH2) 2 CH NH 2-Br-6-F-4-Me-phenyl 138.9 CH3 (MeOCH ) 2 CH NH 2-C1-4, 6-Me 2 -phenyl a CH 3 (MeOCH 2 ) 2 CH NH 2-Cl-4-OMe-6-Me- 128.3 phenyl CH3 (MeOCH 2 ) CH NH 2,4-Me 2 -6-MeθCH 2 - phenyl Cl MeOC 2 H4 (MeOCH 2 ) CH NH 2 , 4-Me 2 -6-MeO-phenyl Cl MeOC 2 H4 (MeOCH 2 ) CH NH 4-Br-2, 6-Me 2 -phenyl 138.6 Cl MeOC H4 (MeOCH 2 ) CH NH 2-C1-4, 6-Me 2 -phenyl Cl MeOC 2 H4 (MeOCH 2 ) CH NH 2,4-Me 2 -6-MeOCH - phenyl Cl {MeOCH 2 ) 2 CH NH 2 , 4-Me 2 -6-MeO-phenyl Cl (MeOCH 2 ) 2 CH NH 4-Br-2,6-Me 2 -phenyl 152.1 Cl (MeOCH ) 2 CH NH 2-C1-4, 6-Me -phenyl 132.8 Cl (MeOCH ) 2 CH NH 2,4-Me 2 -6-MeOCH 2 - phenyl Cl MeOCH 2 (Me)CH NH 2, 4-Me 2 -6-MeO-phenyl Cl MeOCH 2 (Me)CH NH 4-Br-2 , 6-Me 2 -phenyl Cl EtOCH 2 (Et)CH NH 4-Br-2 , 6-Me 2 -phenyl Cl EtOCH 2 (Me)CH NH 4-Br-2 , 6-Me 2 -phenyl Cl MeOCH 2 (Et) CH NH 4-Br-2 , 6-F 2 -phenyl CH 3 MeOC 2 H4 (MeOCH )CH NH 2-Br-4, 6-Me 2 -phenyl CH MeOC 2 H4 {MeOCH ) CH NH 2 , 4-Me -6-SMe-phenyl CH 3 MeOC H4 (MeOCH ) CH NH 2,4-Me -6-S0 Me- phenyl CH 3 MeOC H4 (MeOCH 2 ) CH NH 4-NMe -2, 6-Me 2 - phenyl CH3 MeOC 2 H4 (MeOCH 2 ) CH NH 2 , 4-Cl -6-Me-phenyl CH3 MeOC 2 H4 (MeOCH 2 ) CH NH 4-C1-2 , 6-Me 2 -phenyl CH 3 MeθC H4 (MeOCH 2 ) CH NH 2 , 6-Me 2 -4-SMe-phenyl CH 3 MeOC H4 (MeOCH 2 ) CH NH 2 , 6-Me 2 -4-0Me-phenyl CH 3 MeOC 2 H4 (MeOCH 2 ) CH NH 2 , 6-Me 2 -4-S0 Me-phenyl CH 3 MeOC H4 (MeOCH 2 ) CH NH 4-MeC(0)-2,6-Me 2 - phenyl CH 3 (MeOCH ) 2 CH NH 4-Br-2, 6-Me 2 -phenyl CH 3 (MeOCH ) 2 CH NH 4-MeC(0)-2,6-Me 2 - phenyl CH3 (MeOCH ) 2 CH NH 2 , 6-Me2~4-SMe-phenyl CH3 (MeOCH 2 ) CH NH 2 , 6-Me 2 -4-S0 Me-phenyl CH (MeOCH 2 ) 2 CH NH 4-NMe 2 -2, 6-Me -phenyl CH3 (MeOCH ) CH NH 2-NMe -4, 6-Me 2 -phenyl Cl MeOCH 2 <Et)CH NH 2 , 6-Me 2 -4-SMe-phenyl 104.9 Cl MeOCH 2 (Et)CH NH 2 , 6-Me 2 -4-S0 Me-phenyl 79 Cl MeOCH 2 (Et)CH NH 2-C1-4 , 6-Me 2 -phenyl 116 . 7 80 Cl MeθCH 2 (Et)CH NH 4-Br-6-OMe-2-Me-phenyl 147 . 8 81 Cl (MeθCH 2 ) CH NH 2, 6-Me 2 -4-SMe-phenyl 158 .9 82 Cl (MeθCH 2 ) 2 CH NH 2, 6-Me 2 -4-S0 Me-phenyl 83 Cl (MeθCH ) 2 CH NH 4-Br-6-OMe-2-Me-phenyl 175.5 84 CH3 Et 2 CH NH 2,4, 6- e3-phenyl 109 84a CH 3 Et 2 CH NH 2-C1-4 , 6-Me 2 -phenyl 133.8 84b CH3 Et 2 CH NH 2-Cl-4-OMe-6-Me- 121.9 phenyl 84c CH CH3 Et 2 CH NH 2,4,6-Me3-phenyl 79.3 84d CH 2 CH3 Et CH NH 2-C1-4 , 6-Me2-ρhenyl 95.6 85 Br Et CH NH 2, 4, 6- e3-phenyl MS = 378 86 Br Et 2 CH NH 2-Br-4-iPr-phenyl 87 Br Et 2 CH NEt 2-Br-4-iPr-phenyl 88 Br Et CH NH 2 , 4-Br2-phenyl 89 Br Et 2 CH NEt 2 , 4-Br -phenyl 90 Br Et CH NEt 2,4, 6-Mβ3-phenyl 91 Br Et 2 CH NEt 2,4, 6-Me3-phenyl 92 Br MeOCH 2 (Et ) CH NH 2,4,6-Me3-phenyl 93 Br Et 2 CH NH 2-Br-4,6- ( MeO) 2 - phenyl 94 Br Et CH NH 2-CN-4 , 6-Me 2 -phenyl 95 Br MeθCH (Et)CH NH 2-Br-4,6-(MeO) - phenyl 96 Br MeθCH 2 (Et)CH NH 2-1-4 , 6-Me 2 -phenyl 97 Br MeOCH 2 (Et)CH NH 2, 6-Me -4-Br-phenyl 98 Br MeθCH 2 (Et)CH NH 2-I-4-Cl-6-Me-phenyl 99 Br (MeOCH 2 ) 2 CH NH 2,4, 6-Me3-phenyl 100 Br MeOCH 2 {Et)CH NH 2 , 6-Me 2 -4-SMe-phenyl 101 Br MeOCH (Et)CH NH 2,6-Me 2 -4-S0 2 Me- phenyl 102 Br MeOCH 2 (Et)CH NH 2-Cl-4,6-Me 2 -phenyl 103 Br MeOCH (Et)CH NH 2-Me-4-Br-6-OMe- phenyl 104 CH3 Et 2 CH NH 2,4, 6-Me3~pyrid-3-yl 105 CH3 Et 2 CH NH 4 , 6-Me 2 -pyrid-3-yl 106 CH3 Et 2 CH NH 2-Br-6-Me-pyrid-3-yl 107 CH 3 Et CH NH 2-Br-6-OMe-pyrid-3-yl 108 CH 3 Et 2 CH NH 2 , 6-Me 2 -pyrιd-3-yl 109 CH Et 2 CH NH 2-Cl-6-Me-pyπd-3-yl 110 CH 3 Et 2 CH NH 2-Cl-6-OMe-pyrιd-3-yl 111 CH 3 MeOCH 2 (Et)CH NH 2,4, 6-Me3-pyrιd-3-yl 112 CH3 MeOCH 2 (Et)CH NH 4, 6-Me 2 -pyrιd-3-yl 113 CH3 MeOCH 2 (Et)CH NH 2-Br-6-Me-pyrιd-3-yl 114 CH 3 (MeOCH 2 ) 2 CH NH 2-Br-6-OMe-pyrιd-3-yl 115 CH3 (MeOCH 2 ) 2 CH NH 2 , 6-Me2-pyrιd-3-yl 116 CH3 (MeOCH 2 ) 2 CH NH 2-ci-6-Me-pyπd-3-yl 117 CH3 (MeOCH 2 ) 2 CH NH 2-Cl-6-OMe-pyrιd-3-yl 118 CH 3 MeOCH (Et)CH NH 2-Br-6-OMe-pyπd-3-yl 119 CH 3 MeOCH 2 (Et)CH NH , 6-Me 2 -pyrιd-3-yl 120 CH 3 MeOCH 2 (Et)CH NH 2-Cl-6-Me-pyrιd-3-yl 121 CH3 MeOCH 2 (Et)CH NH 2-Cl-6-OMe-pyrιd-3-yl 120 CH3 (MeOCH 2 ) 2 CH NH 2,4, 6-Me3-pyrιd-3-yl 123 CH3 (MeθCH ) CH NH 4 , 6-Me 2 -py ιd-3-yl 124 CH3 (MeOCH 2 ) 2 CH NH 2-Br-6-Me-pyrιd-3-yl 125 Cl Et 2 CH NH 2-Br-6-OMe-pyrιd-3-yl 124 Cl Et 2 CH NH 2 , 6-Me 2 -py ιd-3-yl 127 Cl Et 2 CH NH 2-Cl-6-Me-pyπd-3-yl 128 Cl Et 2 CH NH 2-Cl-6-OMe-pyrιd-3-yl 129 Cl MeOCH 2 (Et)CH NH 2,4, 6-Me 3 -pyrιd-3-yl 130 Cl MeOCH 2 (Et)CH NH 4 , 6-Me 2 -pyrιd-3-yl 131 Cl MeOCH 2 (Et)CH NH 2-Br-6-Me-pyrιd-3-yl 132 Cl Et CH NH 2,4, 6-Me 3 -pyrιd-3-yl 133 Cl Et 2 CH NH 4 , 6-Me 2 -pyrιd-3-yl 134 Cl Et 2 CH NH 2-Br-6-Me-pyrιd-3-yl 135 Cl MeOCH 2 (Et)CH NH 2-Br-6-OMe-pyrιd-3-yl 136 Cl MeOCH 2 {Et)CH NH 2 , 6-Me 2 -pyrιd-3-yl 137 Cl MeOCH 2 (Et)CH NH 2-Cl-6-Me-pynd-3-yl 138 Cl MeOCH (Et)CH NH 2-Cl-6-OMe-pyrιd-3-yl 139 Cl (MeOCH ) 2 CH NH 2-Br-6-OMe-pyrιd-3-yl 140 Cl (MeOCH 2 ) 2 CH NH 2 , 6-Me 2 -pyrιd-3-yl 141 Cl (MeOCH 2 ) 2 CH NH 2-Cl-6-Me-pyrιd-3-yl 142 Cl (MeOCH 2 ) 2 CH NH 2-Cl-6-OMe-pyrιd-3-yl 143 Cl (MeOCH 2 )2CH NH 2,4, 6-Me 3 -pyrιd-3-yl 144 Cl (MeOCH 2 ) 2 CH NH 4, 6-Me -pyrid-3-yl 145 Cl (MeOCH 2 ) 2 CH NH 2-Br-6-Me-pyrid-3-yl 146 Et 2 CH CH 3 NH 2,4,6-Me3-phenyl 147 Et 2 CH CH 3 NH 2, 6-Me -4-Br-phenyl 148 Et 2 CH CH3 NH 2-Br-4-iPr-phenyl 149 MeOCH 2 (Et)CH CH3 NH 2,4, 6-Me3-phenyl 150 MeθCH 2 (Et)CH CH3 NH 2 , 6-Me 2 -4-Br-phenyl 151 MeOCH (Et)CH CH3 NH 2-Cl-4,6-Me 2 -phenyl 152 (MeOCH 2 ) 2 CH CH3 NH 2,4, 6- e3 -phenyl 153 (MeOCH 2 ) 2 CH CH 3 NH 2 , 6-Me 2 -4-Br-phenyl 154 (MeθCH ) CH CH3 NH 2-C1-4 , 6-Me 2 -phenyl 155 Et CH CH3 NH 2-Br-4, 6- (MeO) 2-phenyl 156 Et 2 CH CH 3 NH 2-C1-4, 6-Me2-phenyl 400 CH 3 Me(Et)CH NH 2,4, 6-Me 3 -phenyl 401 CH 3 Me(Et)CH NH 2-C1-4 , 6-Me2-phenyl 402 CH 3 Me(Et)CH NH 2 , 4-Cl2~6-Me-phenyl 403 CH3 Me(Et)CH NH 2,4, 6-Cl3-phenyl 404 CH 3 Me(Et)CH NH 2 -Me-4-MeO-phenyl 405 CH 3 Me(Et)CH NH 2-ci-4-MeO-phenyl 406 CH3 Me(Et)CH NH 2,4, 6-Me 3 -5-F-phenyl 407 CH 3 Me(Et)CH NH 2 , 5-Me 2 -4-MeO-phenyl 408 CH 3 Me(Et)CH NH 2, 4 -Me 2 -6-MeO-phenyl 409 CH 3 Me(Et)CH NH 2, 6-Cl -4-Me-phenyl 410 CH3 Me(Et)CH NH 2, -Cl -phenyl 411 CH3 Me(Et)CH NH 2-Cl-4-Me-phenyl 412 CH 3 Me(Et)CH NH 2-Me- -Cl-phenyl 413 CH3 Me(Et)CH NH 2-NMe 2 -6-Me-pyrid-5-y1 414 CH3 Me{Et)CH NH 2-NMe 2 -4-Me-pyrid-5-yl 415 CH 3 Me{Et)CH NH 2-Cl-4-MeO-6-Me-phenyl 416 CH3 Me(Et)CH NH 2-Cl-4,6-Me 2 -5-F- phenyl 417 CH 3 Me(Et)CH NH 6-C1-2, 3-dihydro- benzofuran-5-yl 418 CH3 Me(Et)CH NH 6-Me-2, 3-dihydro- benzof ran-5-y1 419 CH 3 Me(n-Pr)CH NH 2 , 4 , 6-Me3 -phenyl 420 CH3 Me(n-Pr)CH NH 2-C1-4, 6-Me 2 -phenyl 421 CH 3 Me(n-Pr)CH NH 2 , 4-Cl 2 -6-Me-phenyl 422 CH3 Me(n-Pr)CH NH 2,4, 6-Cl3-phenyl 423 CH3 Me(n-Pr)CH NH 2 -Me-4-MeO-phenyl 424 CH 3 Me(n-Pr)CH NH 2-Cl-4-MeO-phenyl 425 CH 3 Me(n-Pr)CH NH 2,4, 6-Me3-5-F-phenyl 426 CH 3 Me(n-Pr)CH NH 2 , 5-Me 2 -4-Me0-phenyl 427 CH3 Me(n-Pr)CH NH 2 , 4-Me2-6-Me0-phenyl 428 CH3 Me(n-Pr)CH NH 2 , 6-Cl2-4-Me-phenyl 429 CH3 Me(n-Pr)CH NH 2,4-Cl 2 -phenyl 430 CH3 Me(n-Pr)CH NH 2-Cl-4-Me-phenyl 431 CH3 Me(n-Pr)CH NH 2-Me-4-Cl-phenyl 432 CH3 Me(n-Pr)CH NH 2-NMe 2 -6-Me-pyrid-5-yl 433 CH3 Me(n-Pr)CH NH 2-NMe 2 -4-Me-pyrid-5-yl 434 CH3 Me(n-Pr)CH NH 2-Cl-4-MeO-6-Me-phenyl 435 CH 3 Me(n-Pr)CH NH 2-Cl-4,6-Me -5-F- phenyl 436 CH3 Me(n-Pr)CH NH 6-C1-2, 3-dihydro- benzofuran-5-yl 437 CH3 Me(n-Pr)CH NH 6-Me-2 , 3-dihydro- benzofuran-5-yl 438 CH3 Et CH NH 2 , 4-Cl 2 -6-Me-phenyl 439 CH3 Et 2 CH NH 2,4, 6-Cl3-phenyl 440 CH3 Et2CH NH 2-Me-4-MeO-phenyl 441 CH3 Et 2 CH NH 2-Cl-4-MeO-phenyl 442 CH3 Et 2 CH NH 2,4,6-Me3-5-F-phenyl 443 CH3 Et 2 CH NH 2 , 5-Me 2 -4-MeO-phenyl 444 CH3 Et 2 CH NH 2, 4-Me -6-MeO-phenyl 445 CH3 Et 2 CH NH 2, 6-Cl 2 -4-Me-phenyl 446 CH3 Et 2 CH NH 2, 4-Cl 2 -phenyl 447 CH3 Et 2 CH NH 2-Cl-4-Me-phenyl 448 CH3 Et 2 CH NH 2-Me-4-Cl-phenyl 449 CH3 Et CH NH 2-NMe 2 -6-Me-pyrid-5-yl 450 CH 3 Et CH NH 2-NMe 2 -4-Me-pyrid-5-yl 451 CH3 Et 2 CH NH 2-Cl-4,6-Me 2 -5-F- phenyl 452 CH3 Et 2 CH NH 6-Cl-2,3-dihydro- benzofuran-5-yl 453 CH3 Et2CH NH 6-Me-2,3-dihydro- benzofuran-5-yl 454 CH3 (c-Pr)2CH NH 2,4, 6-Me3-phenyl 455 CH3 (c-Pr) 2 CH NH 2-Cl-4,6-Me 2 -phenyl 456 CH 3 (c-Pr) CH NH 2 , 4-Cl -6-Me-phenyl 457 CH 3 (c-Pr) 2 CH NH 2,4, 6-Cl3-phenyl 458 CH 3 (c-Pr)2CH NH 2-Me-4-MeO-phenyl 459 CH 3 (c-Pr) 2 CH NH 2-Cl-4-Me0-phenyl 460 CH 3 (c-Pr) 2 CH NH 2,4, 6-Me3~5-F-phenyl 461 CH3 (c-Pr) CH NH 2, 5-Me 2 -4-MeO-phenyl 462 CH3 (c-Pr) 2 CH NH 2 , 4-Me -6-MeO-phenyl 463 CH3 (c-Pr) 2 CH NH 2 , 6-Cl 2 -4-Me-phenyl 464 CH3 (c-Pr) 2 CH NH 2,4-Cl2~phenyl 465 CH3 (c-Pr) 2 CH NH 2-ci-4-Me-phenyl 466 CH3 (c-Pr) 2 CH NH 2-Me-4-Cl-phenyl 467 CH3 (c-Pr) 2 CH NH 2-NMe2-6-Me-pyrid-5-yl 468 CH3 (c-Pr) CH NH 2-NMe 2 -4-Me-pyrid-5-yl 469 CH3 (c-Pr)2CH NH 2-Cl-4-MeO-6-Me-phenyl 470 CH3 (c-Pr) 2 CH NH 2-C1- , 6-Me 2 -5-F- phenyl 471 CH3 (c-Pr) 2 CH NH 6-C1-2, 3-dihydro- benzofuran-5-yl 472 CH3 (c-Pr) 2 CH NH 6-Me-2 , 3-dihydro- benzofuran-5-yl 473 CH3 c-Pr (Me) CH NH 2 , 4 , 6-Me3 -phenyl 474 CH3 c-Pr (Me)CH NH 2-C1-4, 6-Me 2 -phenyl 475 CH3 c-Pr(Me)CH NH 2 , 4-Cl2~6-Me-phenyl 476 CH3 c-Pr (Me) CH NH 2,4, 6-Cl3-phenyl 477 CH3 c-Pr (Me) CH NH 2-Me-4-Me0-phenyl 478 CH3 c-Pr(Me)CH NH 2-ci-4-MeO-phenyl 479 CH 3 c-Pr(Me)CH NH 2,4, 6-Me 3 -5-F-phenyl 480 CH3 c-Pr (Me) CH NH 2 , 5-Me 2 -4-Me0-phenyl 481 CH3 c-Pr(Me)CH NH 2, 4-Me 2 -6-MeO-phenyl 482 CH 3 c-Pr(Me)CH NH 2, 6-Cl -4-Me-phenyl 483 CH3 c-Pr (Me) CH NH 2, 4-Cl 2 -phenyl 484 CH3 c-Pr(Me)CH NH 2-Cl-4-Me-phenyl 485 CH3 c-Pr (Me) CH NH 2-Me-4-Cl-phenyl 486 CH3 c-Pr (Me)CH NH 2-NMe -6-Me-pyrid-5-yl 487 CH3 c-Pr(Me)CH NH 2-NMe -4-Me-pyrid-5-yl 488 CH 3 c-Pr(Me)CH NH 2-Cl-4-MeO-6-Me-phenyl 489 CH 3 c-Pr (Me) CH NH 2-Cl-4,6-Me 2 -5-F- phenyl 490 CH 3 c-Pr(Me)CH NH 6-Cl-2,3-dihydro- benzofυran-5-yl 491 CH3 c-Pr (Me) CH NH 6-Me-2, 3-dihydro- benzofuran-5-yl 492 CH 3 c-Pr(Et)CH NH 2 , 4, 6 -Me3 -phenyl 493 CH 3 c-Pr(Et)CH NH 2-C1-4 , 6-Me2-phenyl 494 CH3 c-Pr(Et)CH NH 2, 4-Cl2-6-Me-phenyl 495 CH 3 c-Pr(Et)CH NH 2, 4, 6 -Cl 3 -phenyl 496 CH3 c-Pr (Et)CH NH 2 -Me- 4 -MeO-phenyl 497 CH3 c-Pr(Et)CH NH 2-Cl-4-Me0-phenyl 498 CH3 c-Pr(Et)CH NH 2 , 4 , 6-Me 3 -5-F-phenyl 499 CH 3 c-Pr(Et)CH NH 2 , 5-MΘ2- -MeO-phenyl 500 CH3 c-Pr(Et)CH NH 2 , 4-Me 2 -6-Me0-phenyl 501 CH3 c-Pr(Et)CH NH 2 , 6-Cl 2 -4-Me-phenyl 502 CH3 c-Pr(Et)CH NH 2 , 4-Cl2-phenyl 503 CH3 c-Pr (Et)CH NH 2-Cl-4-Me-phenyl 504 CH3 c-Pr (Et)CH NH 2 -Me- 4 -Cl -phenyl 505 CH 3 c-Pr (Et)CH NH 2-NMe 2 -6-Me-pyrid-5-yl 506 CH3 c-Pr(Et)CH NH 2-NMe 2 -4-Me-pyrid-5-yl 507 CH3 c-Pr(Et)CH NH 2-Cl-4-Me0-6-Me-phenyl 508 CH3 c-Pr(Et)CH NH 2-Cl-4,6-Me -5-F- phenyl 509 CH3 c-Pr(Et)CH NH 6-Cl-2,3-dihydro- benzofuran-5-yl 510 CH3 c-Pr(Et)CH NH 6-Me-2,3-dihydro- benzofuran-5-yl 511 CH3 c-Pr(n-Pr)CH NH 2 , 4, 6-Me3 -phenyl 512 CH3 c-Pr(n-Pr)CH NH 2-C1-4, 6-Me 2 -phenyl 513 CH3 c-Pr (n-Pr)CH NH 2, 4-Cl -6-Me-phenyl 514 CH 3 c-Pr(n-Pr)CH NH 2, 4, 6-Cl3-phenyl 515 CH 3 c-Pr(n-Pr)CH NH 2-Me-4-MeO-phenyl 516 CH 3 c-Pr (n-Pr)CH NH 2-Cl- -MeO-phenyl 517 CH c-Pr (n-Pr)CH NH 2,4, 6-Me3-5-F-phenyl 518 CH 3 c-Pr(n-Pr)CH NH 2, 5-Me 2 - -MeO-phenyl 519 CH3 c-Pr (n-Pr)CH NH 2 , 4-Me -6-MeO-phenyl 520 CH 3 c-Pr (n-Pr)CH NH 2 , 6-Cl 2 -4-Me-phenyl 521 CH 3 c-Pr(n-Pr)CH NH 2, 4-Cl2-phenyl 522 CH3 c-Pr (n-Pr)CH NH 2-Cl-4-Me-phenyl 523 CH3 c-Pr (n-Pr)CH NH 2_Me-4-Cl-phenyl 524 CH 3 c-Pr(n-Pr)CH NH 2-NMe 2 -6-Me-ρyrid-5-yl 525 CH3 c-Pr (n-Pr)CH NH 2-NMθ2-4-Me-pyrid-5-yl 526 CH3 c-Pr(n-Pr)CH NH 2-Cl-4-MeO-6-Me-phenyl 527 CH3 c-Pr (n-Pr)CH NH 2-Cl-4,6-Me 2 -5-F- phenyl 528 CH3 c-Pr (n-Pr)CH NH 6-C1-2, 3-dihydro- benzofuran-5-yl 529 CH3 c-Pr(n-Pr)CH NH 6-Me-2 , 3-dihydro- benzofuran-5-yl 530 CH3 c-Pr (n-Bu)CH NH 2,4, 6-Me 3 -phenyl 531 CH3 c-Pr (n-Bu)CH NH 2-C1-4, 6-Me -phenyl 532 CH3 c-Pr(n-Bu)CH NH 2 , 4-Cl 2 -6-Me-phenyl 533 CH3 c-Pr (n-Bu)CH NH 2,4, 6-Cl 3 -phenyl 534 CH3 c-Pr(n-Bu)CH NH 2-Me-4 -MeO-phenyl 535 CH3 c-Pr (n-Bu)CH NH 2-Cl-4-MeO-phenyl 536 CH3 c-Pr (n-Bu)CH NH 2,4, 6-Me 3 -5-F-phenyl 537 CH3 c-Pr (n-Bu)CH NH 2 , 5-Me2-4-MeO-phenyl 538 CH3 c-Pr(n-Bu)CH NH 2 , 4-Me -6-MeO-phenyl 539 CH 3 c-Pr(n-Bu)CH NH 2 , 6-Cl 2 -4-Me-phenyl 540 CH3 c-Pr(n-Bu)CH NH 2, 4-Cl2-phenyl 541 CH3 c-Pr (n-B )CH NH 2-Cl-4-Me-phenyl 542 CH3 c-Pr(n-Bu)CH NH 2-Me-4-Cl-phenyl 543 CH3 c-Pr (n-Bu)CH NH 2-NMe2-6-Me-pyrid-5-yl 544 CH3 c-Pr(n-Bu)CH NH 2-NMe2-4-Me-pyrid-5-yl 545 CH3 c-Pr(n-Bu)CH NH 2-Cl-4-MeO-6-Me-phenyl 546 CH3 c-Pr (n-Bu)CH NH 2 -Cl-4,6-Me 2 -5-F- phenyl 547 CH 3 c-Pr(n-Bu)CH NH 6-C1-2, 3-dihydro- benzofuran-5-yl 548 CH 3 c-Pr (n-Bu)CH NH 6-Me-2,3-dihydro- benzofuran-5-yl 549 CH 3 c-PrCH2 (Et)CH NH 2 , 4, 6-Me 3 -phenyl 550 CH 3 c-PrCH 2 (Et)CH NH 2-C1-4, 6-Me2-phenyl 551 CH 3 c-PrCH (Et)CH NH 2 , 4-Cl2-6-Me-phenyl 552 CH 3 c-PrCH 2 (Et)CH NH 2, 4, 6-Cl3~phenyl 553 CH 3 c-PrCH 2 (Et)CH NH 2 -Me-4-MeO-phenyl 554 CH 3 c-PrCH (Et)CH NH 2-Cl-4-MeO-phenyl 555 CH 3 c-PrCH 2 (Et)CH NH 2, 4, 6-Me 3 -5-F-phenyl 556 CH 3 c-PrCH 2 (Et)CH NH 2 , 5-Me2- -MeO-phenyl 557 CH3 c-PrCH 2 (Et)CH NH 2 , 4-Me2-6-MeO-phenyl 558 CH3 c-PrCH (Et)CH NH 2 , 6-Cl 2 -4-Me-phenyl 559 CH3 c-PrCH 2 (Et)CH NH 2, 4-Cl2-phenyl 560 CH3 c-PrCH (Et)CH NH 2-Cl-4-Me-phenyl 561 CH3 c-PrCH 2 (Et)CH NH 2-Me-4-Cl-phenyl 562 CH3 c-PrCH (Et)CH NH 2-NMe2-6-Me-pyrid-5-yl 563 CH3 c-PrCH 2 (Et)CH NH 2-NMe2-4-Me-pyrid-5-yl 564 CH3 c-PrCH 2 (Et)CH NH 2-Cl-4-MeO-6-Me-phenyl 565 CH3 c-PrCH 2 (Et)CH NH 2-Cl-4,6-Me 2 -5-F- phenyl 566 CH3 c-PrCH 2 (Et)CH NH 6-Cl-2,3-dihydro- benzofuran-5-yl 567 CH3 c-PrCH2 (Et)CH NH 6-Me-2, 3-dihydro- benzofuran-5-yl Compounds that can be synthesized using synthetic Scheme 6 or Scheme 7 are listed in Table 2 Table 2 Ex . No. Rl R3 Y λr mp 200 CH3 Et2CH NH 2 , 4-Br 2 -phenyl 201 CH3 Et2CH NH 2-Br-4-iPr-phenyl 202 CH 3 Et 2 CH NEt 2 , 4-B 2 -phenyl 203 CH3 Et 2 CH NEt 2-Br-4-iPr-phenyl 204 CH3 Et 2 CH NH 2,4, 6-Me 3 -ρhenyl 133 205 CH3 Et 2 CH NEt 2,4, 6-Me3-phenyl 206 CH3 MeOCH 2 (Et)CH NH 2,4, 6-Me3-phenyl 207 CH3 Et 2 CH NH 2-Br-4 , 6- (MeO) 2-phenyl 208 CH3 MeOCH 2 (Et)CH NH 2-Br-4, 6- (MeO) 2 -phenyl 209 CH3 MeOCH 2 ( Et ) CH NH 2-C1-4, 6- (MeO)2-phenyl 210 CH 3 MeOCH 2 (Et)CH NH 2, 4-Me 2 -6-I-phenyl 211 CH3 MeOCH 2 (Et)CH NH 2-CN-4 , 6-Me2-phenyl 212 CH3 MeOCH 2 (Et)CH NH 2-Br-4 , 6-Me2-phenyl 213 CH3 MeOCH 2 (Et)CH NH 4-Br-2, 6- e2-phenyl 214 CH3 MeOCH 2 (Et)CH NH 4-MeC(0)-2, 6-Me2-phenyl 215 CH3 MeOCH 2 (Et)CH NH 2-MeC(0) -4, 6-Me2-phenyl 216 CH3 MeOCH 2 (Et)CH NH 2 , 4-Me2-6-SMe-phenyl 217 CH3 MeOCH 2 (Et)CH NH 2 , 4-Me2-6-S02Me-phenyl 218 CH 3 MeOCH (Et)CH NH 4-Cl-2-I-6-Me-phenyl 219 CH3 (MeOCH 2 ) 2 CH NH 2,4, 6-Me 3 -phenyl 220 CH 3 Et 2 CH NH 2,4, 6-Me 3 -phenyl 221 CH3 (MeOCH ) CH NH 2, 4-Cl2-6-Me-phenyl 222 CH3 (MeOCH 2 ) 2 CH NH 2 , 4-Br2-6-Me-phenyl 223 CH3 MeOC H4 (MeOCH 2 ) CH NH 2,4, 6-Me 3 -phenyl 224 CH3 (MeOC 2 H4) 2 CH NH 2,4, 6 -Me3 -phenyl 225 CH 3 MeOCH2(Et)CH NH 2 , 4 -Me 2 - 6 -MeO-phenyl 226 CH 3 MeOC 2 H4{MeOCH 2 )CH NH 2, 4-Me 2 - 6 -MeO-phenyl 227 CH 3 MeOC 2 H4(MeOCH 2 )CH NH 2-Br-4, 6-Me 2 -phenyl 228 CH 3 MeOC 2 H4 (MeOCH ) CH NH 2-C1-4, 6-Me 2 -phenyl 229 CH3 MeOC 2 H4 (MeOCH 2 ) CH NH 2 , 4 -Me 2 - 6-MeOCH 2 -phenyl 230 CH3 (MeOCH 2 ) 2 CH NH 2 , 4 -Me 2 - 6 -MeO-phenyl 231 CH3 (MeOCH 2 ) 2 CH NH 4-Br-2 , 6 -Me 2 -phenyl 232 CH3 (MeOCH 2 ) 2 CH NH 2-C1-4, 6-Me 2 -phenyl 233 CH3 (MeOCH 2 ) 2 CH NH 2 , 4 -Me 2 - 6 -MeOCH 2 -phenyl 234 CH3 MeOCH (Me)CH NH 2 , 4 -Me 2 - 6 -MeO-phenyl 235 CH 3 MeOCH (Me)CH NH 2-Br-4 , 6-Me2~phenyl 236 CH3 EtOCH 2 (Et)CH NH 2-Br-4 , 6-Me2-phenyl 237 CH3 EtOCH 2 (Me)CH NH 2-Br-4 , 6-Me2-phenyl 238 CH3 MeOCH (Et)CH NH 2-Br-4 , 6-F 2 -phenyl 239 Et2CH CH3 NH 2,4, 6 -Me3 -phenyl 240 Et2CH CH3 NH 4-Br-2 , 6-Me 2 -phenyl 241 Et2CH CH3 NH 2-Br-4-iPr-phenyl 242 MeOCH 2 (Et)CH CH3 NH 2,4, 6-Me3 -phenyl 243 MeOCH 2 (Et)CH CH3 NH 4-Br-2 , 6-Me 2 -phenyl 244 MeOCH 2 (Et)CH CH3 NH 2-C1- , 6-Me2-phenyl 245 (MeOCH 2 ) 2 CH CH3 NH 2,4, 6-Me 3 -phenyl 246 (MeOCH 2 ) 2 CH CH3 NH 4-Br-2 , 6-Me 2 -phenyl 247 (MeOCH 2 )2CH CH3 NH 2-C1-4, 6-Me 2 -phenyl 248 Et 2 CH CH3 NH 2-Br-4 , 6- (MeO) 2 -phenyl 249 Et 2 CH CH3 NH 2-C1-4, 6-Me 2 -phenyl 250 CH3 Et 2 CH NH 2-C1-4, 6-Me2-phenyl 251 CH3 Et 2 CH NH 2 , 4-Cl2-6-Me-phenyl 252 CH3 Et 2 CH NH 2,4,6-Cl3-phenyl 253 CH3 Et CH NH 2 -Me-4 -MeO-phenyl 254 CH3 Et 2 CH NH 2-Cl-4-MeO-phenyl 255 CH3 Et 2 CH NH 2,4, 6-Me3-5-F-phenyl 256 CH3 Et 2 CH NH 2 , 5-Me -4-MeO-phenyl 257 CH3 Et 2 CH NH 2 , 4 -Me - 6 -MeO-phenyl 258 CH3 Et 2 CH NH 2 , 6-Cl2-4-Me-phenyl 259 CH3 Et 2 CH NH 2,4-Cl 2 -phenyl 260 CH3 Et 2 CH NH 2-Cl-4-Me-phertyl 261 CH3 Et 2 CH NH 2-Me-4-Cl-phenyl 262 CH 3 Et 2 CH NH 2-NMe 2 -6-Me-pyrid-5-yl 263 CH 3 Et CH NH 2-NMe -4-Me-pyrid-5-yl 264 CH 3 Et 2 CH NH 2-Cl-4-MeO-6-Me-phenyl 265 CH 3 Et 2 CH NH 2-Cl-4,6-Me -5-F- phenyl 266 CH3 Et 2 CH NH 6-Cl-2,3-dihydro- benzofuran-5-yl 267 CH 3 Et 2 CH NH 6-Me-2 , 3-dihydro- benzofuran-5-yl 268 CH 3 MeOCH 2 (Et)CH NH 2-C1-4, 6-Me 2 -phenyl 269 CH3 MeOCH 2 (Et)CH NH 2 , 4-Cl 2 -6-Me-phenyl 270 CH 3 MeOCH 2 (Et)CH NH 2,4,6-Cl3-phenyl 271 CH 3 MeOCH 2 (Et)CH NH 2-Me- 4-MeO-phenyl 272 CH3 MeOCH 2 (Et)CH NH 2-Cl-4-MeO-phenyl 273 CH 3 MeOCH 2 (Et)CH NH 2,4, 6-Me3-5-F-phenyl 274 CH 3 MeOCH 2 (Et)CH NH 2 , 5-Me 2 -4 -MeO-phenyl 275 CH3 MeOCH 2 (Et)CH NH 2 , 6-Cl2"4-Me-phenyl 276 CH3 MeOCH 2 (Et)CH NH 2 , 4-Cl 2 -phenyl 277 CH3 MeOCH 2 (Et)CH NH 2-Cl-4-Me-phenyl 278 CH3 MeOCH 2 (Et)CH NH 2-Me-4-Cl-phenyl 279 CH3 MeOCH 2 (Et)CH NH 2-NMe 2 -6-Me-pyrid-5-yl 280 CH3 MeOCH 2 (Et)CH NH 2-NMe2-4-Me-pyrid-5-yl 281 CH3 MeOCH 2 (Et)CH NH 2-Cl-4-MeO-6-Me-phenyl 282 CH3 MeOCH 2 (Et)CH NH 2-Cl-4,6-Me 2 -5-F- phenyl 283 CH3 MeOCH 2 (Et)CH NH 6-C1-2, 3-dihydro- benzofuran-5-yl 284 CH3 MeOCH 2 ( Et ) CH NH 6-Me-2 , 3-dihydro- benzofuran-5-yl Compounds wherein Y = Oxygen that can be synthesized using synthetic Scheme 3 are listed in Table 3 Table 3 EX No Rl 3 Y λr mp/°C 700 Cl Et 2 CH O 2 -Br-4-iPr -phenyl 701 Cl Et 2 CH 0 2 , 4 -Br 2 -phenyl 702 Cl Et2CH 0 2,4, 6-Me3 -phenyl 703 Cl MeOCH2 (Et)CH 0 2,4, 6-Me3 -phenyl 116 704 Cl Et2CH 0 2-Br-4, 6- (MeO) 2 - phenyl 705 Cl Et 2 CH 0 2-CN-4 , 6-Me 2 -phenyl 706 Cl MeOCH 2 ( Et ) CH o 2-Br-4, 6- (MeO) - phenyl 707 Cl MeOCH 2 (Et)CH o 2-Cl-4,6-(MeO) 2 - phenyl 708 Cl MeOCH 2 (Et)CH 0 2-1-4 , 6 -Me 2 -phenyl 709 Cl MeOCH 2 (Et)CH 0 2 -CN-4,6-Me 2 -phenyl 710 Cl MeOCH 2 (Et)CH 0 2-Br-4, 6-Me 2 -phenyl 711 Cl MeOCH (Et)CH 0 4-Br-2, 6-Me2-phenyl 712 Cl MeOCH 2 (Et)CH 0 4-MeCO-2 , 6-Me 2 -phenyl 713 Cl MeOCH 2 (Et)CH 0 4-MeCO-2-OMe-6-Me- phenyl 714 Cl MeOCH 2 (Et)CH 0 2-MeCO-4, 6-Me -phenyl 715 Cl MeOCH 2 (Et)CH 0 4, 6-Me 2 -2-SMe-phenyl 716 Cl MeOCH 2 (Et)CH 0 4, 6-Me 2 -2-S0 Me-phenyl 717 Cl MeOCH (Et)CH 0 4-Cl-2-I-6-Me-phenyl 718 Cl (MeOCH ) 2 CH 0 2,4, 6 -Me 3 -phenyl 719 Cl phenyl 0 2,4,6-Me3-phenyl 720 CH3 MeOCH 2 (Et)CH 0 2, 4-Br 2 -phenyl 721 CH 3 MeOCH 2 (Et)CH 0 2-Br-4-iPr-phenyl 722 CH3 MeOCH 2 (Et)CH O 2,4, 6-Me3-phenyl 723 CH3 MeOCH 2 (Et)CH 0 2-C1-4, 6-Me 2 -phenyl 724 CH3 (MeOCH 2 ) 2 CH 0 2,4, 6-Me3-phenyl 725 CH3 (MeOCH 2 ) CH 0 2, 4-Cl -6-Me-phenyl 726 Cl (MeOCH 2 ) CH O 2 , 4-Cl 2 -6-Me-phenyl 727 Cl (MeOCH 2 ) 2 CH 0 2 , 4-Br 2 -6-Me-phenyl 728 CH 3 MeOC 2 H4 (MeOCH 2 ) CH 0 2,4, 6-Me3 -phenyl 729 Cl MeOC 2 H4 (MeOCH2 ) CH O 2,4, 6-Me 3 -phenyl 730 Cl MeOC 2 H4(MeOCH 2 )CH 0 4-Br-2-0Me-6-Me- phenyl 731 Cl (MeOC2H4)2CH O 2,4, 6-Me3 -phenyl 732 Cl MeOCH2 (Et)CH O 2 , 4-Me 2 -6-MeO-phenyl 733 Cl MeOC 2 H4 (MeOCH 2 ) CH O 2 , 4-Me2-6-Me0-phenyl 734 CH 3 MeOC 2 H4 (MeOCH2 ) CH O 2 , 4 -Me 2 -6-MeO-phenyl 735 CH 3 MeOC2H4 (MeOCH2)CH O 4-Br-2 , 6-Me 2 -ρhenyl 736 CH3 MeOC2H4 (MeOCH 2 ) CH O 2-C1-4, 6-Me 2 -phenyl 737 CH3 MeOC 2 H4 (MeOCH2 ) CH o 2 , 4 -Me 2 -6 -MeOCH 2 - phenyl 738 CH3 (MeOCH2) 2 CH o 2 , 4-Me 2 - 6-MeO-phenyl 739 CH 3 (MeOCH2) 2 CH o 4-Br-2 , 6-Me 2 -phenyl 740 CH 3 (MeOCH 2 )2CH o 2-Br-6-F-4-Me-phenyl 741 CH 3 (MeOCH 2 ) 2 CH 0 2-C1-4, 6-Mβ2-phenyl 742 CH 3 (MeOCH 2 ) CH 0 2-Cl-4-OMe-6-Me- phenyl 743 CH3 (MeOCH 2 ) 2 CH 0 2,4-Me 2 -6-MeOCH 2 - phenyl 744 Cl MeOC H4 (MeOCH 2 ) CH o 2 , 4-Me -6-MeO-phenyl 745 Cl MeOC 2 H4 (MeOCH 2 ) CH 0 4-Br-2 , 6-Me 2 -phenyl 746 Cl MeOC 2 H4 (MeOCH 2 ) CH o 2-C1-4, 6-Me 2 -phenyl 747 Cl MeOC 2 H4 (MeOCH 2 ) CH 0 2,4-Me 2 -6-MeOCH 2 - phenyl 748 Cl ( MeOCH 2 ) 2 CH 0 2 , 4-Me 2 - 6-MeO-phenyl 749 Cl (MeOCH 2 ) 2 CH 0 4-Br-2 , 6-Me2-phenyl 750 Cl (MeOCH 2 ) CH 0 2-C1-4 , 6-Me2-phenyl 751 Cl (MeOCH ) 2 CH 0 2 , 4-Me 2 -6-MeOCH - phenyl 752 Cl MeOCH2 (Me)CH 0 2 , 4-Me 2 _ 6-MeO-phenyl 753 Cl MeOCH2 (Me)CH 0 4-Br-2 , 6-Me -phenyl 754 Cl EtOCH2 (Et)CH 0 4-Br-2 , 6-Me 2 -phenyl 755 Cl EtOCH 2 (Me)CH 0 4-Br-2 , 6-Me 2 -phenyl 756 Cl MeOCH 2 (Et)CH 0 4-Br-2, 6-F2-phenyl 757 CH3 MeOC 2 H (MeOCH 2 ) CH 0 2-Br-4, 6-Me 2 -phenyl 758 CH 3 MeOC H4 (MeOCH 2 ) CH 0 2 , 4-Me -6-SMe-phenyl 759 CH3 MeOC H4 (MeOCH 2 ) CH 0 2, 4-Me -6-S0 Me- phenyl 760 CH 3 MeOC 2 H4 (MeOCH 2 ) CH 0 4-NMe -2 , 6-Me 2 - phenyl 761 CH3 MeOC H (MeOCH ) CH O 2 , 4-Cl 2 -6-Me-phenyl 762 CH 3 MeOC 2 H4 (MeOCH 2 ) CH 0 4-C1-2 , 6-Me 2 -phenyl 763 CH 3 MeOC 2 H4 (MeOCH 2 ) CH 0 2 , 6-Me 2 - -SMe-pheny1 764 CH3 MeOC 2 H4 (MeOCH 2 ) CH 0 2, 6-Me2-4-OMe-phenyl 765 CH 3 MeOC 2 H4 (MeOCH2 ) CH 0 2, 6-Me 2 -4-S0 Me-phenyl 766 CH 3 MeOC2H4 (MeOCH2 ) CH 0 4-MeC(0)-2, 6-Me2- phenyl 767 CH3 (MeOCH2)2CH 0 4-Br-2 , 6-Me 2 -phenyl 768 CH3 (MeOCH 2 ) 2 CH 0 4-MeC(0)-2, 6-Me - phenyl 769 CH3 (MeOCH 2 ) 2 CH 0 2 , 6-Me 2 -4-SMe-phenyl 770 CH3 (MeOCH 2 ) 2 CH 0 2 , 6-Me2-4-S0 Me-phenyl 771 CH3 (MeOCH ) 2 CH 0 4-NMe 2 -2 , 6-Me2~phenyl 772 CH3 (MeOCH 2 ) CH 0 2-NMe -4 , 6-Me2-phenyl 773 Cl MeOCH 2 (Et)CH 0 2 , 6-Me2-4-SMe-phenyl 774 Cl MeOCH 2 (Et)CH 0 2, 6-Me 2 -4-S0 Me-phenyl 775 Cl MeOCH ( Et ) CH o 2-C1-4, 6-Me 2 -phenyl 776 Cl MeOCH 2 (Et)CH 0 4-Br-6-OMe-2-Me-phenyl 777 Cl (MeOCH 2 ) 2 CH 0 2 , 6-Me2~4-SMe-phenyl 778 Cl (MeOCH 2 ) 2 CH 0 2, 6-Me 2 -4-S0 2 Me-phenyl 779 Cl (MeOCH 2 ) 2 CH 0 4-Br-6-0Me-2-Me-phenyl 780 CH 3 Et 2 CH 0 2 , 4 , 6-Me3 -phenyl 781 CH3 Et 2 CH 0 2-C1-4, 6-Me -phenyl 782 CH3 Et CH 0 2-Cl-4-0Me-6-Me- phenyl 783 CH 3 Et CH O 2,4, 6-Me 3 -pyrιd-3-yl 784 CH 3 Et 2 CH 0 4 , 6-Me2-pyrιd-3-yl 785 CH3 Et 2 CH 0 2 -Br- 6 -Me-pyr id- 3-yl 786 CH 3 Et 2 CH 0 2-Br-6-0Me-pyrιd-3-yl 787 CH3 Et 2 CH 0 2 , 6-Me2-pyrιd-3-yl 788 CH3 Et 2 CH O 2-Cl-6-Me-pyrιd-3-yl 789 CH3 Et CH 0 2-Cl-6-OMe-pyrιd-3-yl 790 CH3 MeOCH 2 (Et)CH 0 2,4, 6-Me3-pyrιd-3-yl 791 CH3 MeOCH (Et)CH 0 4, 6-Me2-pyπd-3-yl 792 CH3 MeOCH 2 (Et)CH 0 2-Br-6-Me-pyπd 3-yl 793 CH3 (MeOCH 2 ) 2 CH O 2-Br-6-OMe-pyπd-3 -yl 794 CH3 (MeOCH 2 ) 2 CH 0 2 , 6-Me 2 -pyrιd-3-yl 795 CH3 (MeOCH 2 ) 2 CH 0 2-Cl-6-Me-pyrιd 3-yl 796 CH3 (MeOCH 2 ) CH 0 2-Cl-6-OMe-pyrιd-3-yl 797 CH3 MeOCH 2 (Et)CH O 2-Br-6-OMe-pyrιd-3-yl 798 CH3 MeOCH 2 { Et ) CH O 2 , 6-Me2~pyrιd-3-yl 799 CH3 MeOCH 2 (Et)CH 0 2-Cl-6-Me-pyrιd-3-yl 800 CH3 MeOCH ( Et ) CH 0 2-Cl-6-OMe-py ιd-3-yl 801 CH3 (MeOCH 2 ) 2 CH 0 2,4, 6-Me3-pyrιd-3-yl 802 CH3 (MeOCH 2 ) CH 0 4 , 6-Me2-pyrιd-3-yl 803 CH3 (MeOCH ) 2 CH 0 2 Br 6-Me-pyπd-3 yl 804 Cl Et 2 CH 0 2-Br-6-OMe-pyrιd-3-yl 805 Cl Et 2 CH 0 2 , 6-Me2-pyrιd-3-yl 806 Cl Et 2 CH 0 2-Cl-6-Me-pyπd-3-yl 807 Cl Et 2 CH 0 2-Cl-6-OMe-pyrιd-3-yl 808 Cl MeOCH 2 (Et)CH 0 2,4, 6-Me3-pyrιd-3-yl 809 Cl MeOCH2 (Et)CH 0 4, 6-Me -pynd-3-yl 810 Cl MeOCH 2 (Et)CH 0 2 -Br- 6 -Me-pyr id- 3-yl 811 Cl Et 2 CH 0 2,4, 6-Me3-pyrιd-3-yl 812 Cl Et 2 CH 0 4, 6-Me 2 -pyrιd-3-yl 813 Cl Et CH 0 2 -Br- 6 -Me-pyr id- 3-yl 814 Cl MeOCH 2 ( Et ) CH 0 2-Br-6-OMe-pyrιd-3-yl 815 Cl MeOCH2 (Et)CH 0 2 , 6-Me 2 -pyrιd-3-yl 816 Cl MeOCH2 (Et)CH 0 2-Cl-6-Me-pyπd-3-yl 817 Cl MeOCH2 (Et)CH 0 2-Cl-6-OMe-pyπd-3-yl 818 Cl (MeOCH 2 ) 2 CH 0 2-Br-6-OMe-pyrid-3-yl 819 Cl (MeOCH 2 ) 2 CH 0 2, 6-Me -pyrid-3-yl 820 Cl (MeOCH ) 2 CH 0 2-Cl-6-Me-pyrid-3-yl 821 Cl (MeOCH 2 ) CH 0 2-Cl-6-OMe-pyrid-3-yl 822 Cl (MeOCH ) 2 CH 0 2,4, 6-Me3~pyrid-3-yl 823 Cl (MeOCH 2 ) 2 CH 0 4 , 6-Me 2 -pyrid-3-yl 824 Cl (MeOCH ) 2 CH 0 2 -Br- 6 -Me-pyr id- 3-yl 825 CH3 Me(Et)CH O 2,4, 6- e3 -phenyl 826 CH 3 Me(Et)CH O 2-C1-4, 6-Me2~phenyl 827 CH3 Me(Et)CH 0 2, 4-Cl 2 -6-Me-phenyl 828 CH 3 Me(Et)CH 0 2, 4, 6 -Cl 3 -phenyl 829 CH3 Me(Et)CH O 2 -Me-4 -MeO-phenyl 830 CH3 Me(Et)CH 0 2-Cl-4-MeO-phenyl 831 CH3 Me ( Et ) CH 0 2,4, 6-Me3-5-F-phenyl 832 CH3 Me(Et)CH O 2 , 5-Me2-4-MeO-phenyl 833 CH 3 Me(Et)CH O 2 , 4-Me2-6-MeO-phenyl 834 CH3 Me(Et)CH 0 2, 6-Cl 2 -4-Me-phenyl 835 CH3 Me(Et)CH 0 2, 4 -Cl 2 -phenyl 836 CH3 Me(Et)CH 0 2-Cl-4-Me-phenyl 837 CH3 Me(Et)CH 0 2-Me-4-Cl-phenyl 838 CH3 Me(Et)CH 0 2-NMe 2 -6-Me-pyrid-5-yl 839 CH 3 Me(Et)CH 0 2-NMe 2 -4-Me-pyrid-5-yl 840 CH3 Me(Et)CH 0 2-Cl-4-MeO-6-Me-phenyl 841 CH3 Me(Et)CH 0 2-Cl-4,6-Me -5-F- phenyl 842 CH3 Me(Et)CH 0 6-Cl-2,3-dihydro- benzof uran-5-yl 843 CH3 Me(Et)CH 0 6-Me-2,3-dihydro- benzofuran-5-yl 844 CH3 Me(n-Pr)CH 0 2,4, 6-Me3 -phenyl 845 CH3 Me(n-Pr)CH 0 2-C1-4, 6 -Me 2 -phenyl 846 CH3 Me(n-Pr)CH 0 2, 4-Cl 2 -6-Me-phenyl 847 CH3 Me(n-Pr)CH 0 2,4,6-Cl 3 -phenyl 848 CH3 Me(n-Pr)CH 0 2 -Me-4 -MeO-phenyl 849 CH3 Me(n-Pr)CH 0 2 -Cl -4 -MeO-phenyl 850 CH3 Me(n-Pr)CH 0 2,4, 6-Me 3 -5-F-phenyl 851 CH3 Me(n-Pr)CH 0 2 , 5 -Me 2 - 4 -MeO-phenyl 852 CH 3 Me(n-Pr)CH 0 2 , 4-Me 2 -6-MeO-phenyl 853 CH 3 Me(n-Pr)CH 0 2, 6-Cl 2 -4-Me-phenyl 854 CH 3 Me(n-Pr)CH 0 2, 4-Cl2-phenyl 855 CH 3 Me(n-Pr)CH 0 2-Cl-4-Me-phenyl 856 CH 3 Me(n-Pr)CH 0 2-Me-4-Cl-phenyl 857 CH 3 Me(n-Pr)CH 0 2-NMe2~6-Me-pyrid-5-yl 858 CH3 Me(n-Pr)CH 0 2-NMe2-4-Me-pyrid-5-yl 859 CH 3 Me(n-Pr)CH 0 2-Cl-4-Me0-6-Me-phenyl 860 CH Me(n-Pr)CH 0 2-C1-4, 6-Me 2 -5-F- phenyl 861 CH3 Me(n-Pr)CH 0 6-C1-2, 3-dihydro- benzofuran-5-yl 862 CH3 Me(n-Pr)CH 0 6-Me-2,3-dihydro- benzofuran-5-yl 863 CH3 c-Pr 2 CH 0 2,4,6 -Me3-phenyl 864 CH 3 c-Pr 2 CH 0 2-C1-4, 6-Me -phenyl 865 CH3 c-Pr 2 CH 0 2 , 4-Cl 2 -6-Me-phenyl 866 CH3 c-Pr 2 CH 0 2,4,6-Cl3-phenyl 867 CH3 c-Pr 2 CH 0 2-Me-4-MeO-phenyl 868 CH3 c-Pr 2 CH 0 2-Cl-4-MeO-phenyl 869 CH3 c-Pr 2 CH 0 2,4, 6-Me3-5-F-phenyl 870 CH3 c-Pr CH 0 2 , 5-Me 2 -4-Me0-phenyl 871 CH3 c-Pr 2 CH 0 2 , 4-Me2~6-MeO-phenyl 872 CH3 c-Pr 2 CH 0 2 , 6-Cl 2 -4-Me-phenyl 873 CH3 c-Pr 2 CH 0 2, 4-Cl2-phenyl 874 CH3 c-Pr 2 CH 0 2-Cl-4-Me-phenyl 875 CH 3 c-Pr 2 CH 0 2-Me-4 -Cl-phenyl 876 CH 3 c-Pr 2 CH 0 2-NMe2~6-Me-pyrid-5-yl 877 CH3 c-Pr 2 CH 0 2-NMe2-4-Me-pyrid-5-yl 878 CH3 c-Pr 2 CH 0 2-Cl-4-Me0-6-Me-phenyl 879 CH3 c-Pr 2 CH 0 2-Cl-4,6-Me 2 -5-F- phenyl 880 CH3 c-Pr 2 CH 0 6-Cl-2,3-dihydro- benzofuran-5-yl 881 CH 3 c-Pr 2 CH 0 6-Me-2 , 3-dihydro- benzofuran-5-yl 882 CH3 c-Pr (Me)CH 0 2,4,6- e3 -phenyl 883 CH 3 c-Pr (Me)CH 0 2-C1-4, 6-Me2-phenyl 884 CH 3 c-Pr(Me)CH 0 2 , 4-Cl2-6-Me-phenyl 885 CH3 c-Pr(Me)CH 0 2,4, 6-Cl -phenyl 886 CH 3 c-Pr (Me) CH 0 2-Me-4-MeO-phenyl 887 CH3 c-Pr (Me) CH 0 2-Cl-4-MeO-phenyl 888 CH 3 c-Pr(Me)CH 0 2,4, 6-Me3-5-F-phenyl 889 CH 3 c-Pr (Me)CH 0 2 , 5-Me 2 -4-MeO-phenyl 890 CH3 c-Pr(Me)CH 0 2 , 4-Me 2 -6-MeO-phenyl 891 CH3 c-Pr (Me) CH 0 2 , 6-Cl 2 -4-Me-phenyl 892 CH 3 c-Pr (Me) CH O 2, 4-Cl 2 -phenyl 893 CH3 c-Pr(Me)CH 0 2-Cl-4-Me-phenyl 894 CH3 c-Pr (Me)CH 0 2-Me-4-Cl-phenyl 895 CH 3 c-Pr (Me) CH 0 2-NMe2-6-Me-pyrid-5-yl 896 CH 3 c-Pr(Me)CH 0 2-NMe2-4-Me-pyrid-5-yl 897 CH3 c-Pr(Me)CH 0 2-Cl-4-MeO-6-Me-phenyl 898 CH3 c-Pr (Me) CH o 2-Cl-4,6-Me 2 -5-F- phenyl 899 CH 3 c-Pr(Me)CH 0 6-C1-2, 3-dihydro- benzofuran-5-yl 900 CH3 c-Pr(Me)CH 0 6-Me-2,3-dihydro- benzofuran-5-yl 901 CH 3 c-Pr(Et)CH 0 2,4, 6-Me3-phenyl 902 CH 3 c-Pr (Et)CH 0 2-C1-4 , 6-Me 2 -phenyl 903 CH 3 c-Pr (Et)CH 0 2, 4-Cl 2 -6-Me-phenyl 904 CH3 c-Pr(Et)CH 0 2,4, 6-CI3 -phenyl 905 CH3 c-Pr(Et)CH 0 2-Me-4-MeO-phenyl 906 CH 3 c-Pr(Et)CH 0 2-Cl-4-MeO-phenyl 907 CH3 c-Pr(Et)CH 0 2,4, 6-Me3-5-F-phenyl 908 CH 3 c-Pr(Et)CH 0 2 , 5-Me2-4-MeO-phenyl 909 CH3 c-Pr (Et)CH 0 2 , 4-Me 2 -6-MeO-phenyl 910 CH 3 c-Pr(Et)CH 0 2 , 6-Cl2-4-Me-phenyl 911 CH3 c-Pr(Et)CH 0 2, 4-Cl 2 -phenyl 912 CH3 c-Pr(Et)CH 0 2 -Cl-4-Me-phenyl 913 CH3 c-Pr(Et)CH 0 2-Me-4-Cl-phenyl 914 CH3 c-Pr(Et)CH 0 2-NMe 2 -6-Me-pyrid-5-yl 915 CH3 c-Pr(Et)CH 0 2-NMe 2 -4-Me-pyrid-5-yl 916 CH 3 c-Pr(Et)CH 0 2 -Cl-4-MeO-6-Me-phenyl 917 CH 3 c-Pr(Et)CH O 2-C1-4 , 6-Me 2 - 5-F- phenyl 918 CH 3 c-Pr (Et)CH O 6-C1-2, 3-dihydro- benzofuran-5-yl 919 CH 3 c-Pr (Et)CH O 6-Me-2,3-dihydro- benzofuran-5-yl 920 CH3 c-Pr (n-Pr)CH O 2, 4 , 6-Me3-phenyl 921 CH 3 c-Pr(n-Pr)CH O 2-C1-4, 6-Me 2 -phenyl 922 CH 3 c-Pr (n-Pr)CH O 2, 4-Cl 2 -6-Me-phenyl 923 CH3 c-Pr (n-Pr)CH O 2, 4, 6 -CI3 -phenyl 924 CH 3 c-Pr (n-Pr)CH O 2-Me-4-MeO-phenyl 925 CH 3 c-Pr (n-Pr)CH O 2-Cl-4-MeO-phenyl 926 CH 3 c-Pr (n-Pr)CH O 2, 4, 6-Me 3 -5-F-phenyl 927 CH 3 c-Pr (n-Pr)CH O 2 , 5-Me -4-MeO-phenyl 928 CH3 c-Pr (n-Pr)CH O 2,4-Me 2 -6-MeO-phenyl 929 CH 3 c-Pr (n-Pr)CH O 2, 6-Cl2-4-Me-phenyl 930 CH 3 c-Pr (n-Pr)CH O 2, -Cl 2 -phenyl 931 CH 3 c-Pr(n-Pr)CH O 2-Cl-4-Me-phenyl 932 CH3 c-Pr (n-Pr)CH O 2-Me-4-Cl-phenyl 933 CH3 c-Pr (n-Pr)CH O 2-NMe -6-Me-pyrid-5-yl 934 CH3 c-Pr(n-Pr)CH O 2-NMe2"4-Me-pyrid-5-yl 935 CH 3 c-Pr (n-Pr)CH O 2-Cl-4-MeO-6-Me-phenyl 936 CH3 c-Pr (n-Pr)CH O 2~Cl-4,6-Me -5-F- phenyl 937 CH3 c-Pr (n-Pr)CH O 6-C1-2, 3-dihydro- benzofuran-5-yl 938 CH3 c-Pr (n-Pr)CH O 6-Me-2,3-dihydro- benzofuran-5-yl 939 CH3 c-Pr(n-Bu)CH O 2 , 4 , 6-Me3~phenyl 940 CH3 c-Pr(n-Bu)CH O 2-C1-4, 6-Me 2 -phenyl 941 CH3 c-Pr (n-Bu)CH O 2 , 4-Cl 2 -6-Me-phenyl 942 CH3 c-Pr (n-Bu)CH 0 2, 4, 6-Cl3 -phenyl 943 CH 3 c-Pr (n-Bu)CH O 2-Me-4-MeO-phenyl 944 CH3 c-Pr (n-Bu)CH O 2-Cl-4-MeO-phenyl 945 CH 3 c-Pr (n-Bu)CH O 2 , 4, 6-Me3-5-F-phenyl 946 CH 3 c-Pr(n-Bu)CH O 2 , 5-Me -4-MeO-phenyl 947 CH3 c-Pr (n-Bu)CH O 2 , 4-Me 2 -6-MeO-phenyl 948 CH3 c-Pr(n-Bu)CH 0 2 , 6 -Cl 2 -4-Me-phenyl 949 CH 3 c-Pr(n-Bu)CH 0 2 , 4 -Cl 2 -phenyl 950 CH 3 c-Pr (n-Bu)CH 0 2 -Cl - 4 -Me-phenyl 951 CH 3 c-Pr(n-Bu)CH 0 2 -Me-4-Cl-phenyl 952 CH 3 c-Pr(n-Bu)CH 0 2 -NMe 2 - 6-Me-pyrid- 5 -yl 953 CH3 c-Pr(n-Bu)CH 0 2 -NMe 2 -4 -Me-pyrid- 5 -yl 954 CH3 c-Pr(n-Bu)CH 0 2 -Cl-4-Me0- 6-Me-phenyl 955 CH3 c-Pr (n-Bu)CH 0 2 -Cl -4 , 6-Me 2 - 5-F- phenyl 956 CH3 c-Pr(n-Bu)CH 0 6-Cl- 2 , 3 -dihydro- benzofuran-5-yl 957 CH3 c-Pr(n-Bu)CH 0 6-Me-2 , 3 -dihydro- benzofuran-5-yl 958 CH 3 c-PrCH 2 (Et)CH 0 2,4,6-Me -phenyl 959 CH 3 c-PrCH 2 (Et)CH 0 2-C1-4, 6-Me 2 -phenyl 960 CH 3 c-PrCH (Et)CH 0 2, 4-Cl2-6-Me-phenyl 961 CH3 c-PrCH 2 (Et)CH 0 2,4, 6-Cl3-phenyl 962 CH 3 c-PrCH 2 (Et)CH 0 2-Me-4-MeO-phenyl 963 CH 3 c-PrCH 2 (Et)CH 0 2-Cl-4-MeO-phenyl 964 CH 3 c-PrCH 2 (Et)CH O 2,4, 6-Me3-5-F-phenyl 965 CH3 c-PrCH 2 (Et)CH 0 2 , 5-Me 2 - -MeO-phenyl 966 CH3 c-PrCH 2 (Et)CH 0 2 , 4-Me2~6-MeO-phenyl 967 CH3 c-PrCH 2 (Et)CH 0 2 , 6-Cl2-4-Me-phenyl 968 CH3 c-PrCH (Et)CH 0 2 , 4-Cl 2 -phenyl 969 CH3 c-PrCH 2 (Et)CH 0 2-Cl-4-Me-phenyl 970 CH3 c-PrCH 2 (Et)CH 0 2-Me-4-Cl-phenyl 971 CH3 c-PrCH 2 (Et)CH o 2-NMe 2 -6-Me-pyrid-5-yl 972 CH 3 c-PrCH 2 (Et)CH 0 2-NMe -4-Me-pyrid-5-yl 973 CH3 c-PrCH 2 (Et)CH 0 2-Cl-4-MeO-6-Me-phenyl 974 CH3 c-PrCH 2 (Et)CH 0 2-Cl-4,6-Me 2 -5-F- phenyl 975 CH3 c-PrCH 2 (Et)CH 0 6-Cl-2,3-dihydro- benzofuran-5-yl 976 CH3 c-PrCH 2 (Et)CH 0 6-Me-2, 3-dihydro- benzofuran-5-yl 977 CH Et 2 CH 0 2, 4-Cl 2 -6-Me-phenyl 978 CH3 Et 2 CH 0 2,4,6-Cl3-phenyl 979 CH3 Et 2 CH 0 2 -Me- 4 -MeO-phenyl 980 CH 3 Et 2 CH 0 2 -Cl- 4 -MeO-phenyl 981 CH3 Et 2 CH 0 2, 4, 6-Me3-5-F-phenyl 982 CH 3 Et 2 CH 0 2, 5 -Me - 4 -MeO-phenyl 983 CH 3 Et 2 CH O 2 , 4-Me 2 -6 -MeO-phenyl 984 CH 3 Et 2 CH O 2, 6-Cl 2 -4-Me-phenyl 985 CH 3 Et 2 CH O 2, 4-Cl 2 -phenyl 986 CH3 Et 2 CH O 2-Cl-4-Me-phenyl 987 CH3 Et 2 CH O 2-Me-4-Cl-phenyl 988 CH 3 Et 2 CH O 2-NMe 2 -6-Me-pyrid-5-yl 989 CH3 Et 2 CH O 2-NMe 2 -4-Me-pyrid-5-yl 990 CH3 Et 2 CH O 2-Cl-4,6-Me2-5-F- phenyl 991 CH3 Et 2 CH O 6-C1-2, 3-dihydro- benzofur n-5-yl 992 CH3 Et 2 CH O 6-Me-2,3-dihydro- benzof uran-5-yl Additional compounds, wherein Y = oxygen that can be synthesized using synthetic Scheme 6 or Scheme 7 are listed in Table 4 Table 4 Ex . No . Rl R3 Y Ar mp 1000 CH 3 Et 2 CH 0 2 , 4 , 6-Me 3 -phenyl 1001 CH3 Et 2 CH O 2-C1-4, 6-Me 2 -phenyl 1002 CH3 Et 2 CH 0 2, 4-Cl 2 -6-Me-phenyl 1003 CH3 Et 2 CH O , 4, 6-C13 -phenyl 1004 CH3 Et 2 CH O 2-Me-4-MeO-phenyl 1005 CH3 Et2CH O 2-Cl-4-MeO-phenyl 1006 CH3 Et 2 CH O 2 , 4 , 6-Me 3 -5-F-phenyl 1007 CH3 Et CH O 2 , 5-Me2- -MeO-phenyl 1008 CH3 Et 2 CH O 2 , 4-Me 2 - 6 -MeO-phenyl 1009 CH3 Et 2 CH O 2 , 6-Cl 2 -4-Me-phenyl 1010 CH3 Et2CH O 2 , 4-Cl2-phenyl 1011 CH3 E 2CH O 2-Cl-4-Me-phenyl 1012 CH3 Et2CH 0 2-Me-4-Cl-phenyl 1013 CH 3 Et2CH 0 2-NMe2-6-Me-pyrid-5-yl 1014 CH 3 Et 2 CH O 2-NMe2~4-Me-pyrid-5-yl 1015 CH3 Et2CH O 2-Cl-4-MeO-6-Me-phenyl 1016 CH3 Et2CH O 2-Cl-4,6-Me 2 -5-F- phenyl 1017 CH3 Et 2 CH 0 6-Cl-2,3-dihydro- benzofuran-5-yl 1018 CH3 Et 2 CH O 6-Me-2 , 3 -dihydro- benzofuran-5-yl Utility CRF-R1 Receptor Binding Assay for the Evaluation of Biological Activity The following is a description of the isolation of cell membranes containing cloned human CRF-R1 receptors for use in the standard binding assay as well as a description of the assay itself. Messenger RNA was isolated from human hippocampus . The mRNA was reverse transcribed using oligo (dt) 12-18 and the coding region was amplified by PCR from start to stop codons The resulting PCR fragment was cloned into the EcoRV site of pGEMV, from whence the insert was reclaimed using Xhol + Xbal and cloned into the Xhol + Xbal sites of vector pm3ar ( which contains a CMV promoter, the SV40 't' splice and early poly A signals, an Epstein-Barr viral origin of replication, and a hygromycin selectable marker) . The resulting expression vector, called phchCRFR was transfected in 293EBNA cells and cells retaining the episome were selected in the presence of 400 mM hygromycin. Cells surviving 4 weeks of selection in hygromycin were pooled, adapted to growth in suspension and used to generate membranes for the binding assay described below. Individual aliquots containing approximately 1 x 10^ of the suspended cells were then centrifuged to form a pellet and frozen. For the binding assay a frozen pellet described above containing 293EBNA cells transfected with hCRFRl receptors is homogenized in 10 ml of ice cold tissue buffer ( 50 mM HEPES buffer pH 7.0, containing 10 mM MgCl2, 2 mM EGTA, 1 mg/1 aprotinin, 1 mg/ml leupeptin and 1 mg/ml pepstatin) . The homogenate is centrifuged at 40,000 x g for 12 min and the resulting pellet rehomogenized in 10 ml of tissue buffer. After another centrifugation at 40,000 x g for 12 min, the pellet is resuspended to a protein concentration of 360 mg/ml to be used in the assay. Binding assays are performed in 96 well plates; each well having a 300 ml capacity. To each well is added 50 ml of test drug dilutions (final concentration of drugs range from 10- 10 - IO- 5 M) , 100 ml of 125 I-ovine-CRF ( 125 I-o-CRF) (final concentration 150 pM) and 150 ml of the cell homogenate described above. Plates are then allowed to incubate at room temperature for 2 hours before filtering the incubate over GF/F filters (presoaked with 0.3% polyethyleneimine) using an appropriate cell harvester. Filters are rinsed 2 times with ice cold assay buffer before removing individual filters and assessing them for radioactivity on a gamma counter. Curves of the inhibition of 125 I-o-CRF binding to cell membranes at various dilutions of test drug are analyzed by the iterative curve fitting program LIGAND [P.J. Munson and D. Rodbard, Anal . Biochem. 107:220 (1980)], which provides Ki values for inhibition which are then used to assess biological activity. A compound is considered to be active if it has a Ki value of less than about 10000 nM for the inhibition of CRF. Compounds with a Ki less than 100 nM for the inhibition of CRF are desirable. A number of compounds of the invention have been made and tested in the above assay and shown to have Ki values less than 100 nM thus confirming the utility of the invention. Inhibition of CRF-Stiraulated Adenylate Cvclase Activity Inhibition of CRF-stimulated adenylate cyclase activity was performed as described by G. Battaglia et al . Synapse 1:572 (1987). Briefly, assays were carried out at 37° C for 10 min in 200 ml of buffer containing 100 mM Tris-HCl (pH 7.4 at 37° C) , 10 mM MgCl2 , 0.4 mM EGTA, 0.1% BSA, 1 mM isobutylmethylxanthine (IBMX) , 250 units/ml phosphocreatine kinase, 5 mM creatine phosphate, 100 mM guanosine 5 ' -triphosphate, 100 nM oCRF, antagonist peptides (concentration range 10 ~ 9 to 10 ~ ^ m ) and 0.8 mg original wet weight tissue (approximately 40-60 mg protein) . Reactions were initiated by the addition of 1 mM ATP/3 2 P] ATP (approximately 2-4 mCi/tube) and terminated by the addition of 100 ml of 50 mM Tris-HCL, 45 mM ATP and 2% sodium dodecyl sulfate. In order to monitor the recovery of cAMP, 1 μl of [ 3 H]cAMP (approximately 40,000 dpm) was added to each tube prior to separation. The separation of [ 32 P]cAMP from [ 32 P]ATP was performed by sequential elution over Dowex and alumina columns. Recovery was consistently greater than 80%. A compound of this invention was tested in this assay and found to be active; IC 50 < 10000 nM. In vivo Biological Assay The in vivo activity of the compounds of the present invention can be assessed using any one of the biological assays available and accepted within the art. Illustrative of these tests include the Acoustic Startle Assay, the Stair Climbing Test, and the Chronic Administration Assay. These and other models useful for the testing of compounds of the present invention have been outlined in C.W. Berridge and A.J. Dunn Brain Research Reviews 15:71 (1990) Compounds may be tested in any species of rodent or small mammal. Disclosure of the assays herein is not intended to limit the enablement of the invention. Compounds of this invention have utility in the treatment of inbalances associated with abnormal levels of corticotropin releasing factor in patients suffering from depression, affective disorders, and/or anxiety. Compounds of this invention can be administered to treat these abnormalities by means that produce contact of the active agent with the agent's site of action in the body of a mammal. The compounds can be administered by any conventional means available for use in conjunction with pharmaceuticals either as individual therapeutic agent or in combination of therapeutic agents. They can be administered alone, but will generally be administered with a pharmaceutical carrier selected on the basis of the chosen route of administration and standard pharmaceutical practice. The dosage administered will vary depending on the use and known factors such as pharmacodynamic character of the particular agent, and its mode and route of administration; the recipient's age, weight, and health; nature and extent of symptoms; kind of concurrent treatment; frequency of treatment; and desired effect. For use in the treatment of said diseases or conditions, the compounds of this invention can be orally administered daily at a dosage of the active ingredient of 0.002 to 200 mg/kg of body weight. Ordinarily, a dose of 0.01 to 10 mg/kg in divided doses one to four times a day, or in sustained release formulation will be effective in obtaining the desired pharmacological effect. Dosage forms (compositions) suitable for administration contain from about 1 mg to about 100 mg of active ingredient per unit. In these pharmaceutical compositions, the active ingredient will ordinarily be present in an amount of about 0.5 to 95% by weight based on the total weight of the composition. The active ingredient can be administered orally is solid dosage forms, such as capsules, tablets and powders; or in liquid forms such as elixirs, syrups, and/or suspensions. The compounds of this invention can also be administered parenterally in sterile liquid dose formulations . Gelatin capsules can be used to contain the active ingredient and a suitable carrier such as but not limited to lactose, starch, magnesium stearate, steric acid, or cellulose derivatives. Similar diluents can be used to make compressed tablets. Both tablets and capsules can be manufactured as sustained release products to provide for continuous release of medication over a period of time. Compressed tablets can be sugar-coated or film-coated to mask any unpleasant taste, or used to protect the active ingredients from the atmosphere, or to allow selective disintegration of the tablet in the gastrointestinal tract. Liquid dose forms for oral administration can contain coloring or flavoring agents to increase patient acceptance. In general, water, pharmaceutically acceptable oils, saline, aqueous dextrose (glucose) , and related sugar solutions and glycols, such as propylene glycol or polyethylene glycol, are suitable carriers for parenteral solutions. Solutions for parenteral administration preferably contain a water soluble salt of the active ingredient, suitable stabilizing agents, and if necessary, butter substances. Antioxidizing agents, such as sodium bisulfite, sodium sulfite, or ascorbic acid, either alone or in combination, are suitable stabilizing agents. Also used are citric acid and its salts, and EDTA. In addition, parenteral solutions can contain preservatives such as benzalkonium chloride, methyl- or propyl-paraben, and chlorobutanol . Suitable pharmaceutical carriers are described in "Remington's Pharmaceutical Sciences", A. Osol, a standard reference in the field. Useful pharmaceutical dosage-forms for administration of the compounds of this invention can be illustrated as follows : Capsules A large number of units capsules are prepared by filling standard two-piece hard gelatin capsules each with 100 mg of powdered active ingredient, 150 mg lactose, 50 mg cellulose, and 6 mg magnesium stearate. Soft Gelatin Capsules A mixture of active ingredient in a digestible oil such as soybean, cottonseed oil, or olive oil is prepared and injected by means of a positive displacement was pumped into gelatin to form soft gelatin capsules containing 100 mg of the active ingredient . The capsules were washed and dried. Tablets A large number of tablets are prepared by conventional procedures so that the dosage unit was 100 mg active ingredient, 0.2 mg of colloidal silicon dioxide, 5 mg of magnesium stearate, 275 mg of microcrystalline cellulose, 11 mg of starch, and 98.8 mg lactose. Appropriate coatings may be applied to increase palatability or delayed adsorption. The compounds of this invention may also be used as reagents or standards in the biochemical study of neurological function, dysfunction, and disease.

Claims: Claims : 1. A composition of matter comprising compound of Formula I ( I ) or a pharmaceutically acceptable salt form thereof, wherein Z is CR 2 or N; when Z is CR 2 : Y is NR 4 , O or S(0) n ; Ar is phenyl, naphthyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, 1, 3 , 5-triazinyl, 1, 2 , 4-triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, indolinyl, pyrrolyl, oxazolyl, benzof ranyl , benzothienyl , 2,3 -dihydrobenzof ranyl , 2 , 3 -dihydrobenzothienyl , benzothiazolyl , indazolyl, isoxazolyl or pyrazolyl, each substituted with 0 to 4 R 5 groups; wherein Ar is attached to Y through an unsaturated carbon; R 1 is H, halo, Ci-Cio alkyl, C2-C10 alkenyl, C2- C10 alkynyl, C3-C8 cycloalkyl, C1-C4 haloalkyl, aryl, heterocyclyl, -CN, -OR 7 , -SH, -S(0) n R 13 . -COR 7 , -CONR 6 R 7 , -C02R 7 , -OC(0)R 13 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , -NR 8 C02R 7 , or -NR 6 R 7 , wherein C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl or C3-C8 cycloalkyl is each substituted with 0 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, -CN, -OR 7 , -SH, -S(0) n R 13 , -COR 7 , -C02R 7 , -0C(O)R 13 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , -NR 8 C02R 7 , -NR 6 R 7 , -CONR 6 R 7 , aryl and heterocyclyl; R 2 is H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C 3 -C 6 cycloalkyl, halo, -CN, C1-C4 haloalkyl, -NR 9 R 10 , -NR 9 COR 10 , -NR 9 Cθ2R 10 , -OR 11 , -SH or -S(0) n R 12 ; R 3 is C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C8 cycloalkyl, C1-C4 haloalkyl, aryl, heterocyclyl, -CN, -OR 7 , -S(0)2R 13 . -COR 7 , -CO2R 7 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , -CONR 6 R 7 , -NR 8 C02R 7 , or -NR 6 R 7 , wherein C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl or C3-C8 cycloalkyl is each substituted with 0 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, -CN, -OR 7 , -S(0) n R 13 , -COR 7 , -CO2R 7 , -NR 8 COR 7 , -N(COR ) 2 , -NR 8 CONR 6 R 7 , -NR 8 C02R 7 , -NR 6 R 7 , -CONR 6 R 7 , aryl and heterocyclyl, with the proviso that when R 3 is aryl, Ar is not imidazolyl ; R 4 is H, C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl, wherein C2-C6 alkenyl or C2-C6 alkynyl is optionally substituted with C1-C4 alkyl or C3-C6 cycloalkyl and wherein C1-C6 alkyl is optionally substituted with C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, -OR 7 , -S<0)nR 12 . -C02R 7 , -NR 6 R 7 or -NR 9 COR 10 ; R- 3 is independently selected at each occurrence from C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C6 cycloalkyl, C4-C12 cycloalkylalkyl, aryl, heterocyclyl, -NO2 , halo, -CN, C1-C4 haloalkyl, -NR 6 R 7 , -NR 8 COR 7 , -NR 8 C0 2 R 7 , -OR 7 , -COR 7 , -CO2R 7 , -CONR 6 R 7 , -CON(OR 9 )R 7 , -SH, and -S(0) n R 13 . wherein C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C6 cycloalkyl and C4-C12 cycloalkylalkyl are substituted with 0 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, -NO2, halo, -CN, -OR 7 , -COR 7 , -CO2R 7 , -CONR 6 R 7 , -NR 6 R 7 , -NR 8 COR 7 , -NR 8 C0 2 R 7 and -S(0) n R 13 ; R6 and R 7 are independently selected at each occurrence from H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, C4- C12 cycloalkylalkyl, aryl, aryl (C1-C4 alkyl)-, heterocyclyl, heterocyclyl (C1-C4 alkyl)-, morpholinoethyl, morpholinopropyl and morpholinobutyl; or -NR^R 7 taken together as a whole is piperidine, pyrrolidine, piperazine, N-methyl- piperazine, morpholine or thiomorpholine; wherein C1-C4 alkyl, may be substituted with 0 to 2 substituents independently selected at each occurrence from -OH or C1-C4 alkoxy groups; R 8 is independently at each occurrence H or C1-C4 alkyl; R 9 and R 1* - 1 are independently at each occurrence selected from H, C1 . -C4 alkyl and C3-C6 cycloalkyl; R 11 is H, C1-C4 alkyl, C1 . -C4 haloalkyl, or C3-C6 cycloalkyl; R 12 is C1-C4 alkyl, C1-C4 haloalkyl or -NR 6 R 7 ; R 13 is C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, C4-C12 cycloalkylalkyl, -NR 6 R 7 , aryl, aryl (C1-C4 alkyl)-, heterocyclyl or heterocyclyl (C1-C4 alkyl)-; R 14 is C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, C4-C12 cycloalkylalkyl, -NR 15 R 16 ; R 15 and R 16 are independently selected at each occurrence from H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl and C4- C12 cycloalkylalkyl; or -NR 1 R ( - * - taken together as a whole is piperidine, pyrrolidine, piperazine, N-methyl-piperazine, morpholine or thiomorpholine; aryl is phenyl, biphenyl or naphthyl, each substituted with 0 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, -CN, -OR 15 , -SH, -S(0) n R 14 , -COR 15 , -Cθ2R 15 , -OC(0)R 14 , -N02, -NR 8 COR 15 , -N(COR 15 ) 2 , -NR 8 CONR 15 R 16 , -NR 8 C02R 15 , -NR 15 R 16 and -CONR 15 R 16 ; heterocyclyl is 5- to 10- membered heterocyclic ring which may be saturated, partially unsaturated or aromatic, and which consists of carbon atoms and from 1 to 4 heteroatoms independently selected from the group consisting of N, 0 and S, wherein the heterocyclic ring is substituted with 0 to 3 substituents independently selected at each occurrence from C]_- C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, -CN, -OR 15 , -SH, -S{0) n R 14 , -COR 15 , -C02R 15 , -OC(0)R 14 , -NR 8 COR 15 , -N(C0R 15 ) 2 , -NR 8 CONR 15 R 16 , -NR 8 C02R 15 , -NR 15 R 16 , and -CONR 15 R 16 ; and n is independently at each occurrence 0, 1 or 2 ; and wherein, when Z is N: Y is NR 4 , 0 or S(0) n ; Ar, R 1 , R 4 , R 5 , R6, R 7 , R 8 , R , R10, R11, R 12, R 13, R 14 ; R 15 , R f 5, aryl, heterocyclyl, heterocyclyl and n are as defined above, but R 3 is C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C8 cycloalkyl, C1-C4 haloalkyl, aryl, heterocyclyl, -CN, -S(0)2R 13 . -CO2R 7 , -COR 7 or -CONR 6 R 7 , wherein C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl or C3-C8 cycloalkyl is each substituted with 0 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, -CN, -OR 7 , -S(0) n R 13 , -COR 7 , -CO2R 7 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , -NR 8 Cθ2R 7 , -NR 6 R 7 , -CONR 6 R 7 , aryl and heterocyclyl, with the proviso that when R 3 is aryl, Ar is not imidazolyl . 2. A composition of matter comprising a compound of Claim 1 wherein: Z is CR 2 ; Y is NR 4 , 0, S(0) n; Ar is phenyl, naphthyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, 1, 3 , 5-triazinyl, 1, 2 , 4-triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, indolinyl, pyrrolyl, oxazolyl, benzofuranyl , benzothienyl , 2 , 3-dihydrobenzofuranyl, 2 , 3-dihydrobenzothienyl , benzothiazolyl , indazolyl , isoxazolyl or pyrazolyl, each substituted with 0 to 4 R 5 groups; wherein Ar is attached to Y through an unsaturated carbon; R 1 is H, halo, Ci-Cio alkyl, C2-C10 alkenyl, C2- C10 alkynyl, C3-C8 cycloalkyl, C1-C4 haloalkyl, aryl, heterocyclyl, -CN, -OR 7 , -SH, -S(0) n R 13 . -COR 7 , -CONR 6 R 7 , -Cθ2R 7 , -OC(0)R 13 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 5 R 7 , -NR 8 C02R 7 , or -NR 6 R 7 , wherein C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl or C3-C8 cycloalkyl is each substituted with 0 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, -CN, -OR 7 , -SH, -S(0) n R 13 , -COR 7 , -C02R 7 , -OC(0)R 13 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , -NR 8 Cθ2R 7 , -NR 6 R 7 , -CONR β R 7 , aryl and heterocyclyl ; R 2 is H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C 3 -C 6 cycloalkyl, halo, -CN, C1 . -C4 haloalkyl, -NR 9 R 10 , -NR 9 COR 10 , -NR 9 CO2R 10 i -OR 11 , -SH or -S(0) n R 12 ; R 3 is C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C8 cycloalkyl, C1-C4 haloalkyl, aryl, heterocyclyl, -CN, -OR 7 , -S(0)2R 13 . -COR 7 , -CO2R 7 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , -CONR 6 R 7 . -NR 8 Cθ2R 7 , or -NR β R 7 , wherein C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl or C3-C8 cycloalkyl is each substituted with 0 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, -CN, -OR 7 , -S(0) n R 13 , -COR 7 , -CO2R 7 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , -NR 8 C02R 7 , -NR 6 R 7 , -CONR6R 7 , aryl and heterocyclyl, with the proviso that when R 3 is aryl, Ar is not imidazolyl; R 4 is H, C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl, wherein C2-C6 alkenyl or C2-Cβ alkynyl is optionally substituted with C1-C4 alkyl or C3-C6 cycloalkyl and wherein C1-C6 alkyl is optionally substituted with C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, -OR 7 , -S(0) n R 12 . -C02R 7 , -NR 6 R 7 or -NR 9 COR 10 ; R 5 is independently selected at each occurrence from Ci-Cio alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C6 cycloalkyl, C4-C12 cycloalkylalkyl, aryl, heterocyclyl, -NO2 , halo, -CN, C1-C4 haloalkyl, -NR 6 R 7 , -NR 8 COR 7 , -NR 8 C0 2 R 7 , -OR 7 , -COR 7 , -CO2R 7 , -CONR 6 R 7 , -CON(OR 9 )R 7 , -SH, and -S(0) n R 13 , wherein C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C6 cycloalkyl and C4-C12 cycloalkylalkyl are substituted with 0 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, -NO2 , halo, -CN, -OR 7 , -COR 7 , -CO2R 7 , -CONR 6 R 7 , -NR 6 R 7 , -NR 8 COR 7 , -NR 8 C0 2 R 7 and -S(0) n R 13 ; R^ and R7 are independently selected at each occurrence from H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, C4- C12 cycloalkylalkyl, aryl, aryl(Cι-C4 alkyl)-, heterocyclyl, heterocyclyl (C1-C4 alkyl)-, morpholinoethyl, morpholinopropyl and morpholinobutyl; or NR 6 R 7 taken together as a whole is piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine or thiomorpholine; wherein C1-C4 alkyl, may be substituted with 0 to 2 substituents independently selected at each occurrence from -OH or C1-C4 alkoxy groups; R 8 is independently at each occurrence H or C1-C4 alkyl; R 9 and R 10 are independently at each occurrence selected from H, C1-C4 alkyl and C3-C6 cycloalkyl; R 11 is H, C1-C4 alkyl, C1 . -C4 haloalkyl, or C3-C6 cycloalkyl; R 12 is C1-C4 alkyl, C1-C4 haloalkyl or -NR 6 R 7 ; R 13 is C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3- C6 cycloalkyl, C4-C12 cycloalkylalkyl, -NR 6 R 7 , aryl, aryl (C1-C4 alkyl)-, heterocyclyl or heterocyclyl (Ci- C4 alkyl)-,- R 14 is C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, C4-C12 cycloalkylalkyl, -NR 15 R 16 ; R 5 and R ( 5 are independently selected at each occurrence from H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl and C4- C12 cycloalkylalkyl; or -NR 1 R lf ^ taken together as a whole is piperidine, pyrrolidine, piperazine, N-methyl-piperazine, morpholine or thiomorpholine; aryl is phenyl, biphenyl or naphthyl, each substituted with 0 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, -CN, -OR 15 , -SH, -S(0) n R 14 . -COR 15 , -C02R 15 , -OC(0)R 14 , -N02, -NR 8 COR 15 , -N(COR 15 ) 2 . -NR 8 CONR 15 R 16 , -NR 8 C02R 15 , -NR 15 R 16 and -CONR 15 R 16 ; heterocyclyl is pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl , benzothienyl, benzthiazolyl, isoxazolyl or pyrazolyl, each substituted with 0 to 3 substituents independently selected at each occurrence from Cι~ C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, -CN, -OR 15 , -SH, -S(0) n R 14 , -COR 15 , -CO2R 15 , -OC(0)R 14 , -N02, -NR 8 COR 15 , -N(COR 15 ) 2 , -NR 8 CONR 15 R 16 , -NR 8 C02R 15 , -NR 15 R 16 and -CONR 15 R 16 ; and n is independently at each occurrence 0, 1 or 2. 3. A composition of matter comprising a compound of Claim 2 wherein: Z is CR 2 ; Y is NR 4 or 0; Ar is phenyl or pyridyl, each substituted with 0 to 4 R 5 groups ; R 1 is H, halo, C1-C4 alkyl, cyclopropyl, C1-C4 haloalkyl, -CN, -NR 6 R 7 , -CONR 6 R 7 , -OR 7 , -COR 7 , -C0 2 R 7 or -S(0) n R 13 , wherein C1-C4 alkyl is substituted with 0 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, C3-C6 cycloalkyl, halo, -CN, -OR 7 , -S(0) n R 13 . -COR 7 , -CO2R 7 , -NR 8 COR 7 , -NR 8 C02R 7 , -NR 6 R 7 and aryl; R 2 is H, C1-C4 alkyl, halo, C1 . -C4 haloalkyl; R 3 is C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C8 cycloalkyl, C1-C4 haloalkyl, aryl, heterocyclyl, -CN, -OR 7 , -S(0)2R 13 , -COR 7 , -CO2R 7 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , -CONR 6 R 7 , -NR 8 C02R 7 , or -NR 6 R 7 , wherein C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl or C3-C8 cycloalkyl is each substituted with 0 to 3 substituents independently selected at each occurrence from Ci-Cβ alkyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, halo, -CN, -OR 7 , -S(0) n R 13 , -C0 2 R 7 , -NR 8 COR 7 , -NR 8 CONR 6 R 7 , -NR 8 C0 R 7 , -NR 6 R 7 , aryl and heterocyclyl ; R 4 is H, C1-C6 alkyl or C2-C6 alkenyl, wherein C1-C6 alkyl is optionally substituted with C1-C4 alkyl, C1-C4 haloalkyl, -OR 7 , -S(0) n R 12 , -CO2R 7 , -NR 6 R 7 or -NR- 9 COR 10 ; R 5 is independently selected at each occurrence from C1-C6 alkyl, C 2 -C6 alkenyl, C -C6 alkynyl, C3-C6 cycloalkyl, C4-C8 cycloalkylalkyl, aryl, heterocyclyl, C1-C4 haloalkyl, halo, -CN, -N0 2 , -NR 6 R 7 , -COR 7 , -OR 7 , -CONR 6 R 7 , -CON(OR 9 )R 7 , C0 2 R 7 and -S(0) n R 13 , wherein C1-C6 alkyl, C2-C6 alkenyl, C 2 -C6 alkynyl, C 3 - Cβ cycloalkyl and C4-C8 cycloalkylalkyl are substituted with 0 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, -N0 , halo, -CN, -NR 6 R 7 , COR 7 - -OR 7 , -CONR 6 R 7 , C0 2 R 7 and -S(0) n R 13 ; R^ and R7 are independently selected at each occurrence from H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, C4- C12 cycloalkylalkyl, aryl, aryl(Cχ-C4 alkyl)-, heterocyclyl, heterocyclyl (C1-C4 alkyl)-, morpholinoethyl, morpholinopropyl and morpholinobutyl; or -NR 6 R 7 taken together as a whole is piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine or thiomorpholine; wherein C1-C4 alkyl, may be substituted with 0 to 2 substituents independently selected at each occurrence from -OH or C1-C4 alkoxy groups; R 8 is independently at each occurrence H or C1-C4 alkyl; R 9 and R 10 are independently at each occurrence selected from H, C1-C4 alkyl and C3-C6 cycloalkyl; R 11 is H, C1-C4 alkyl, C1-C4 haloalkyl, or C3-C6 cycloalkyl; R 12 is C1-C4 alkyl, C1-C4 haloalkyl or -NR 6 R 7 ; R 13 is C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, 03- C6 cycloalkyl, C4-C12 cycloalkylalkyl, -NR 6 R 7 , aryl, aryl(Cι-C4 alkyl)-, heterocyclyl or heterocyclyl (Ci- C4 alkyl ) - ; R 14 is C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, C4-C12 cycloalkylalkyl, -NR 15 R 16 ,- R 15 and R ( 5 are independently selected at each occurrence from H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl and C4- C12 cycloalkylalkyl; or -NR 1 R lf ^ taken together as a whole is piperidine, pyrrolidine, piperazine, N-methyl-piperazine, morpholine or thiomorpholine; aryl is phenyl substituted with 0 to 3 substituents independently selected at each occurrence from C1-C 4 alkyl, halo, -CN, -OR 15 , -S(0) n R 14 - -COR 15 , -C02R 15 , -Nθ2, -NR 8 COR 15 , -NR 8 CONR 15 R 16 , -NR 8 C02R 15 and -NR 15 R 16 ; heterocyclyl is pyridyl, pyrimidinyl, triazinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl or pyrazolyl, each substituted with 0 to 3 substituents independently selected at each occurrence from C1 . -C 4 alkyl, halo, -CN, -OR 15 , -S(0) n R 14 - -C02R 15 , -N02, -NR 8 COR 15 , -NR 8 CONR 15 R 16 , -NR 8 C02R 15 , and -NR 15 R 16 ; and n is independently at each occurrence 0 , 1 or 2. 4. A composition of matter comprising compound of Claim 3 wherein: Z is CR 2 ; Y is NR 4 ; Ar is phenyl or pyridyl, each substituted with 0 to 4 R 5 groups ; R 1 is H, halo, C 1 -C 4 alkyl, cyclopropyl, C1 . -C3 haloalkyl, -CN, -NR 6 R 7 , -CONR 6 R 7 , -COR 7 , -C0 2 R 7 , -OR 7 or -S(0) n R 13 wherein C1-C4 alkyl is substituted with 0 to 3 substituents independently selected at each occurrence from C3-C4 cycloalkyl, halo, -CN, -OR 7 , -S(0) n R 13 . -COR 7 , -C02R 7 , -NR 6 R 7 ; R 2 is H; R 3 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C4 haloalkyl or aryl, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or C3-C6 cycloalkyl is each substituted with 0 to 3 substituents independently selected at each occurrence from Cι~Cς, alkyl, C 3 -C 6 cycloalkyl, C 1 -C 4 haloalkyl, halo, -CN, -OR 7 , -S(0) n R 13 , -C0R 7 , -NR 8 COR 7 , -NR 8 CONR 6 R 7 , -NR 8 C0R 7 , -NR 6 R 7 and aryl ; R 4 is H, allyl, or C1 . -C4 alkyl, wherein C1-C4 alkyl is optionally substituted with C1-C4 alkyl, -OR 7 , -S(0)2R 12 / -CO2R 7 , -NR 6 R 7 or -NR 9 COR 10 ; R 5 is independently selected at each occurrence from C 1 -C 6 alkyl, aryl, heterocyclyl, C 1 -C 4 haloalkyl, halo, -CN, -N0 2 , -NR 6 R 7 , -COR 7 , -OR 7 , -CONR 6 R 7 , -CON(OR 9 )R 7 , -C0 2 R 7 and -S(0) n R 13 . wherein Ci-Cβ alkyl is substituted with 0 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, -N0 , halo, -CN, -NR 6 R 7 , COR 7 - -OR 7 , -CONR 6 R 7 , C0R 7 and -S(0) n R 13 ; R^ and R7 are independently selected at each occurrence from H, C1-C4 alkyl, C1-C4 haloalkyl and C2-C8 alkoxyalkyl ; wherein C1-C4 alkyl, may be substituted with 0 to 2 substituents independently selected at each occurrence from -OH or C1-C4 alkoxy groups; R 8 , R 9 and R 10 are independently at each occurrence H or C1-C4 alkyl; R 12 and R 13 are independently at each occurrence C1-C4 alkyl or -NR 6 R 7 ; R 14 is C1-C4 alkyl or -NR 15 R 16 ; R 15 and R 1( 5 are independently at each occurrence H, C1-C4 alkyl or C2-C8 alkoxyalkyl; aryl is phenyl substituted with 0 to 3 substituents independently selected at each occurrence from C 1 -C 4 alkyl, halo, -CN, -OR 15 , -S(0) n R 14 . -COR 15 , -CO2R 15 , -NO2 and -NR 15 R 16 ; and n is independently at each occurrence 0, 1 or 2. 5. A composition of matter comprising compound of Claim 4 wherein: Z is CR 2 ; Y is NR 4 ; Ar is phenyl or pyridyl, each substituted with 2 to 4 R 5 groups ; R 1 is H, Cl, Br, methyl, ethyl, cyclopropyl, or -CN, R 2 is H; R 3 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C4 haloalkyl or aryl, wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or C3-C6 cycloalkyl is each substituted with 0 to 3 substituents independently selected at each occurrence from C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, -CF 3 , halo, -CN, -OR 7 , and aryl; R 4 is H, methyl, ethyl, i-propyl, n-propyl, n-butyl, i-butyl, s-butyl, n-butyl, or allyl; R 5 is independently selected at each occurrence from methyl, ethyl, i-propyl, n-propyl, aryl, -CF 3 , halo, -CN, -N(CH 3 ) 2 , -C(=0)CH 3 , -OCH 3 , -OCH 2 CH 3 , -OCF 3 , and -S(0) 2 CH 3 ; R 14 is C1-C4 alkyl or -NR 15 R 16 ; R 15 and R 1 ^ are independently at each occurrence H, C1-C4 alkyl or C2-C8 alkoxyalkyl; aryl is phenyl substituted with 0 to 3 substituents independently selected at each occurrence from C 1 -C 4 alkyl, halo, -CN, -OR 15 , -S(0) n R 14 . -COR 15 , -C02R 15 , -N02 and -NR 15 R 16 ; and n is independently at each occurrence 0, 1 or 2. 6. A composition of matter comprising compounds of Claim 4 which are: 3- [ (2 , 4-Dibromophenyl ) amino] -5-chloro-l- (1- ethylpropyl) -2 (IH) -pyrazinone; 3-[ [2-Bromo-4- (1-methylethyl) phenyl] amino] -5-chloro-l- ( 1-ethylpropyl) -2 (IH) -pyrazinone; 3- [ (2, 4-Dibromophenyl) ethylamino] -5-chloro-l- (1- ethylpropyl) -2 (IH) -pyrazinone; 3- [ [2-Bromo-4- (1-methylethyl) phenyl] ethylamino] -5- chloro-1- (1-ethylpropyl) -2 (IH) -pyrazinone; 3- [ (2, 4, 6-Trimethylphenyl) amino] -5-chloro-l- (1- ethylpropyl) -2 (IH) -pyrazinone; 3- [ (2,4, 6-Trimethylphenyl) ethylamino] -5-chloro-l- (1- ethylpropyl) -2 (IH) -pyrazinone; (+/-) -3- [ (2,4, 6-Trimethylphenyl) amino] -5-chloro-l- [1- (methoxymethyl)propyl] -2 (IH) -pyrazinone; 3- [ (2-Bromo-4, 6-dimethoxyphenyl) amino] -5-chloro-l- (1- ethylpropyl) -2 (IH) -pyrazinone; 3- t (2-Cyano-4, 6-dimethylphenyl) amino] -5-chloro-l- [1- (methoxymethyl ) propyl ] -2 ( IH) -pyrazinone; (+/-) -3- [ (2-Bromo-4 , 6-diraethoxyphenyl) amino] -5-chloro- 1- [1- (methoxymethyl) propyl] -2 (IH) -pyrazinone; (+/-) -3- [ (2-Chloro-4, 6-dimethoxyphenyl) araino] -5-chloro- 1- [1- (methoxymethyl) propyl] -2 (IH) -pyrazinone; (+/-) -3- [ (4 , 6-Dimethyl-2-iodophenyl) amino] -5-chloro-l- [1- (methoxymethyl) propyl] -2 (IH) -pyrazinone; 3- [ (2-Cyano-4, 6-dimethylphenyl) amino] -5-chloro-l- [1- (methoxymethyl) propyl] -2 (IH) -pyrazinone; (+/-) -3- [ (2-Bromo-4, 6-dimethylphenyl) amino] -5-chloro-l- [1- (methoxymethyl) propyl] -2 (IH) -pyrazinone; (+/-) -3- [ (4-Bromo-2 , 6-dimethylphenyl) amino] -5-chloro-l- [1- (methoxymethyl)propyl] -2 (IH) -pyrazinone; (+/-) -3- [ (4-Acetyl-2, 6-dimethylphenyl) amino] -5-chloro- 1- [1- (methoxymethyl) propyl] -2 (IH) -pyrazinone; (+/-) -3- [ (2-Acetyl-4 , 6-dimethylphenyl) amino] -5-chloro- 1- [1- (methoxymethyl) propyl] -2 (IH) -pyrazinone; (+/-) -3- [ (4, 6-Dimethyl-2-thiomethylphenyl) amino] -5- chloro-1- [1- (methoxymethyl) propyl] -2 (IH) -pyrazinone; (+/-) -3- [ (4, 6-Dimethyl-2-methylsulfonylphenyl) amino] -5- chloro-1- [1- (methoxymethyl) propyl] -2 (IH) -pyrazinone; (+/-) -3- [ (4-Chloro-2-iodo-6-methylphenyl)amino] -5- chloro-1- [1- (methoxymethyl) propyl] -2 (IH) -pyrazinone; 3-[ (2,4, 6-Trimethylphenyl) amino] -5-chloro-l- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone; 3- [ (2,4, 6-Trimethylphenyl) amino] -5-chloro-1-phenyl- 2 (IH) -pyrazinone; (+/-) -3- [ (2, 4-Dibromophenyl) amino] -5-methyl-l- [1- (methoxymethyl )propyl] -2 {IH) -pyrazinone ; (+/-) -3- [ [2-Bromo-4- (1-methylethyl) phenyl] amino] -5- methyl-1- [1- (methoxymethyl) propyl] -2 (IH) -pyrazinone; (+/-)-3-[(2,4, 6-Trimethylphenyl) amino] -5-raethyl-l- [1- (methoxymethyl) propyl] -2 (IH) -pyrazinone; 3-[ (2,4, 6-Trimethylphenyl) amino] -5-methyl-l- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone; 3- [ (2 , 4-Dichloro-6-methylphenyl) amino] -5-methyl-l- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone; 3- [ (2 , 4-Dichloro-6-methylphenyl) amino] -5-chloro-l- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone; 3- [ (2 , 4-Dibromo-6-methylphenyl) amino] -5-chloro-l- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone; (+/-) -3- [ (2,4, 6-Trimethylphenyl) amino] -5-methyl-l- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) -pyrazinone; (+/-) -3- [(2,4, 6-Trimethylphenyl) amino] -5-chloro-l- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) -pyrazinone; 3-[ (2,4, 6-Trimethylphenyl) amino] -5-chloro-l- [1- (2- methoxyethyl) -3-methoxypropyl] -2 (IH) -pyrazinone; (+/-) -3- [ (2, 4-Dimethyl-6-methoxyphenyl) amino] -5-chloro- 1- [1- (methoxymethyl) propyl] -2 (IH) -pyrazinone; {+/-) -3- t (2 , 4-Dimethyl-6-methoxyphenyl) amino] -5-chloro- 1- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) -pyrazinone; (+/-) -3- [ (2, 4-Dimethyl-6-methoxyphenyl) amino] -5-methyl- 1- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) -pyrazinone; (+/-) -3- [ (4-Bromo-2, 6-dimethylphenyl) amino] -5-methyl-l- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) -pyrazinone; (+/-) -3- [ (2-Chloro-4, 6-dimethylphenyl) amino] -5-methyl- 1- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) -pyrazinone; ( +/-) -3- [ [2, 4-Dimethyl-6- (methoxymethyl) phenyl] amino] - 5-methyl-l- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) - pyrazinone; 3- [ (2 , 4-Dimethyl-6-methoxyphenyl) amino] -5-methyl-1- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone; 3- [ (4-Bromo-2 , 6-dimethylphenyl) amino] -5-methyl-l- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone; 3-[ (2-Chloro-4, 6-dimethylphenyl) amino] -5-methyl-l- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone; 3- [ [2, 4-Dimethyl-6- (methoxymethyl)phenyl] amino] -5- methyl-1- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) - pyrazinone; (+/-) -3- [ (2, 4-Dimethyl-6-methoxyphenyl) araino] -5-chloro- 1- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) -pyrazinone; (+/-) -3- [ (4-Bromo-2 , 6-dimethylphenyl) amino] -5-chloro-l- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) -pyrazinone; (+/-) -3- [ (2-Chloro-4, 6-dimethylphenyl) amino] -5-chloro- 1- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) -pyrazinone; (+/-) -3- [ [2, 4-Dimethyl-6- (methoxymethyl) phenyl] amino] - 5-chloro-l- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) - pyrazinone; 3- [ (2, 4-Dimethyl-6-methoxyphenyl) amino] -5-chloro-l- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone; 3- [ (4-Bromo-2 , 6-dimethylphenyl) amino] -5-chloro-l- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone; 3- [ (2-Chloro-4 , 6-dimethylphenyl) amino] -5-chloro-l- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone; 3- [ [2 , 4-Dimethyl-6- (methoxymethyl) phenyl] amino] -5- chloro-1- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) - pyrazinone; (+/-) 3- [ (2 , 4-Dimethyl-6-methoxyphenyl) amino] -5-chloro- 1- (2-methoxy-l-methylethyl) -2 (IH) -pyrazinone; (+/-) 3- [ (4-Bromo-2 , 6-dimethylphenyl) amino] -5-chloro-1- (2-methoxy-l-methylethyl) -2 (IH) -pyrazinone; (+/-) 3- [ (4-Bromo-2, 6-dimethylphenyl) amino] -5-chloro-l- [ 1- ( ethoxymethyl ) propyl] -2 ( IH) -pyrazinone; (+/- ) 3- [ (4-Bromo-2 , 6-dimethylphenyl) amino] -5-chloro-l- (2-ethoxy-l-methylethyl) -2 (IH) -pyrazinone; and (+/-) 3- [ (4-Bromo-2 , 6-difluorophenyl) amino] -5-chloro-l- [1- (methoxymethyl)propyl] -2 (IH) -pyrazinone; (+/-) -3- [ (2-Bromo-4, 6-dimethylphenyl) amino] -5-methyl-1- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) -pyrazinone; (+/-) -3- [ (2 , 4-Dimethyl-6-thiomethylphenyl) amino] -5- methyl-1- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) - pyrazinone; (+/-) -3- [ (2, 4-Dimethyl-6-methylsulfonylphenyl) amino] -5- methyl-1- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) - pyrazinone; (+/-)-3- [ (2, 6-Dimethyl-4- (N,N-dimethylamino) phenyl) - amino] -5-methyl-l- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) - pyrazinone; (+/-) -3- [ (2 , 4-Dichloro-6-methylphenyl) amino] -5-methyl- 1- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) -pyrazinone; (+/-) -3- [ (4-Chloro-2 , 6-dimethylphenyl) amino] -5-methyl- 1- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) -pyrazinone; (+/-)-3-[(2, 6-Dimethyl-4-thiomethylphenyl) amino] -5- methyl-1- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) - pyrazinone; (+/-) -3- [ (2 , 6-Dimethyl-4-methoxyphenyl) amino] -5-methyl- 1- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) -pyrazinone; (+/-) -3- [ (2, 6-Dimethyl-4-methylsulfonylphenyl) amino] -5- methyl-1- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) - pyrazinone; (+/-) -3- [ (4-Acetyl-2 , 6-dimethylphenyl) amino] -5-methyl- 1- [1- (methoxymethyl) -3-methoxypropyl] -2 (IH) -pyrazinone; 3- [ (4-Bromo-2, 6-dimethylphenyl) amino] -5-methyl-l- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone; 3-[ (4-Acetyl-2, 6-dimethylphenyl) amino] -5-methyl-l- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone; 3- [ (2 , 6-Dimethyl-4-thiomethylphenyl) amino] -5-methyl-l- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone; 3- [ (2 , 6-Dimethyl-4-methylsulfonylphenyl) amino] -5- methyl-1- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) - pyrazinone; 3- [ (2 , 6-Dimethyl-4- (N,N-dimethylamino) phenyl) amino] -5- methyl-1- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) - pyrazinone; 3- [ (4, 6-Dimethyl-2- (N,N-dimethylamino) phenyl) amino] -5- methyl-1- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) - pyrazinone; (+/-)3- [ (2, 6-Dimethyl-4-thiomethylphenyl) amino] -5- chloro-1- [1- (methoxymethyl) propyl] -2 (IH) -pyrazinone; (+/-) 3- [ (2 , 6-Dimethyl-4-methylsulfonylphenyl) amino] -5- chloro-1- [1- (methoxymethyl)propyl] -2 (IH) -pyrazinone; (+/-)3- [ (2-Chloro-4, 6-dimethylphenyl) amino] -5-chloro-l- [1- (methoxymethyl ) propyl ] -2 (IH) -pyrazinone; (+/-) 3- [ (4-Bromo-6-methoxy-2-methylphenyl)amino] -5- chloro-1- [1- (methoxymethyl)propyl] -2 (IH) -pyrazinone; 3-[ (2, 6-Dimethyl-4-thiomethylphenyl) amino] -5-chloro-l- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone; 3- [ (2, 6-Dimethyl-4-methylsulfonylphenyl) amino] -5- chloro-l-[l- (methoxymethyl) -2-methoxyethyl] -2 (IH) - pyrazinone; 3- [ (4-Bromo-6-methoxy-2-methylphenyl) amino] -5-chloro-l- [1- (methoxymethyl) -2-methoxyethyl] -2 (IH) -pyrazinone; and 3- [ (2 , 4 , 6-Trimethylphenyl ) mino] -5-methyl-1- ( 1- ethylpropyl ) -2 ( IH) -pyrazinone . 7. A composition of matter comprising compound of Claim 2 wherein: Z is CR 2 ; Y is NR 4 or 0; Ar is phenyl or pyridyl, each substituted with 0 to 4 R 5 groups ; R 1 is H, halo, Ci-Cio alkyl, C2-C10 alkenyl, C2- C10 alkynyl, C3-C8 cycloalkyl, C1-C4 haloalkyl, aryl, heterocyclyl, -CN, -OR 7 , -SH, -S(0) n R 13 - -COR 7 , -CONR 6 R 7 , -C02R 7 , -OC(0)R 13 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , -NR 8 C02R 7 , or -NR 6 R 7 , wherein Cl-Cio alkyl, C2-C10 alkenyl, C2-C10 alkynyl or C3-C8 cycloalkyl is each substituted with 0 to 3 substituents independently selected at each occurrence from Ci-Cβ alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, -CN, -OR 7 , -SH, -S(0) n R 13 , -COR 7 , -C02R 7 , -OC(0)R 13 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , -NR 8 C02R 7 , -NR 6 R 7 , -CONR 6 R 7 , aryl and heterocyclyl; R 2 is H, C 1 -C 4 alkyl, halo, C 1 -C 4 haloalkyl; R 3 is C 1 -C 4 alkyl, C3-C6 cycloalkyl, C 1 -C 4 haloalkyl and -NR 6 R 7 , wherein C1-C4 alkyl is substituted with 0 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, halo, -CN, -OR 7 , -S(0) n R 13 / -COR 7 , -CO2R 7 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , -NR 8 Cθ2R 7 , -NR 6 R 7 and -CONR 6 R 7 ; R 4 is H, C1-C6 alkyl or C2-C6 alkenyl, wherein C1-C6 alkyl is optionally substituted with C1-C4 alkyl, C1.-C4 haloalkyl, -OR 7 , -S(0) n R 12 , -CO2R 7 , -NR 6 R 7 or -NR 9 COR 10 ; R 5 is independently selected at each occurrence from Cl-Cio alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C6 cycloalkyl, C4-C12 cycloalkylalkyl, aryl, heterocyclyl, -NO2 , halo, -CN, C1-C4 haloalkyl, -NR 6 R 7 , -NR 8 COR 7 , -NR 8 C0 2 R 7 , -OR 7 , -COR 7 , -CO2R 7 . -CONR 6 R 7 , -CON(OR 9 )R 7 and -S(0) n R 13 , wherein Cl-Cio alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C6 cycloalkyl and C4-C12 cycloalkylalkyl are substituted with 0 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, -NO2 , halo, -CN, -OR 7 , -COR 7 , -CO2R 7 , -CONR 6 R 7 , -NR 6 R 7 , -NR 8 COR 7 , -NR 8 C0 2 R 7 and -S(0) n R 13 ; R6 and R 7 are independently selected at each occurrence from H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, C4- C12 cycloalkylalkyl, aryl, aryl(Cι-C4 alkyl)-, heterocyclyl, heterocyclyl (C1-C4 alkyl)-, morpholinoethyl, morpholinopropyl and morpholinobutyl; or -NR^R 7 taken together as a whole is piperidine, pyrrolidine, piperazine, N-methyl- piperazine, morpholine or thiomorpholine; wherein C1-C4 alkyl, may be substituted with 0 to 2 substituents independently selected at each occurrence from -OH or C1-C4 alkoxy groups; R 8 is independently at each occurrence H or C1-C4 alkyl; R 9 and R 11 - 1 are independently at each occurrence selected from H, C1-C4 alkyl and C3-C6 cycloalkyl; R 11 is H, C1-C4 alkyl, C1-C4 haloalkyl, or C3-C6 cycloalkyl; R 12 is C1-C4 alkyl, C1-C4 haloalkyl or -NR 6 R 7 ; R 13 is C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, C4-C12 cycloalkylalkyl, -NR 6 R 7 , aryl, aryl(Cι-C4 alkyl)-, heterocyclyl or heterocyclyl (C1-C4 alkyl ) - ; R 14 is C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, C4-C12 cycloalkylalkyl, -NR 15 R 16 ; R 15 and R '- * ' are independently selected at each occurrence from H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl and C4- C12 cycloalkylalkyl; or -NR 1 R ( -- * taken together as a whole is piperidine, pyrrolidine, piperazine, N-methyl-piperazine, morpholine or thiomorpholine; aryl is phenyl or naphthyl, each substituted with 0 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, halo, -CN, -OR 15 , -S(0) n R 14 - -COR 15 , -Cθ2R 15 , -Nθ2 , -NR 8 COR 15 , -NR 8 CONR 15 R 16 , -NR 8 Cθ2R 15 and -NR 15 R 16 ; heterocyclyl is pyridyl, pyrimidinyl, triazinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl or pyrazolyl, each substituted with 0 to 3 substituents independently selected at each occurrence from C 1 -C 4 alkyl, halo, -CN, -OR 15 , -S(0) n R 14 - -C02R 15 , - θ2 , -NR 8 COR 15 , -NR 8 CONR 15 R lβ , -NR 8 C02R 15 , and -NR 15 R 16 ; and n is independently at each occurrence 0, 1 or 2. 8. A composition of matter comprising compound of Claim 7 wherein: Z is CR 2 ; Y is NR 4 ; Ar is phenyl or pyridyl, each substituted with 0 to 4 R 5 groups ; R 1 is H, halo, C -Cs alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, aryl, heterocyclyl, -CN, -OR 7 , -S(0) n R 13 , -COR 7 , -CONR 6 R 7 , -CO2R 7 or -NR 6 R 7 , wherein C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or C3-C6 cycloalkyl is each substituted with 0 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, -CN, -OR 7 , -SH, -S(0) n R 13 , -COR 7 , -C02R 7 , -OC(0)R 13 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , -NR 8 C02R 7 , -NR 6 R 7 , -CONR 6 R 7 , aryl and heterocyclyl; R 2 is H; R 3 is C 1 -C 4 alkyl, C3-C6 cycloalkyl, C 1 -C 4 haloalkyl and -NR 6 R 7 , wherein C1-C4 alkyl is substituted with 0 to 3 substituents independently selected at each occurrence from C3-C6 cycloalkyl, C1-C4 haloalkyl, halo, -CN, -OR 7 , -S(0) n R 13 , -COR 7 , -CO2R 7 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , -NR 8 Cθ2R 7 , -NR 6 R 7 and -CONR 6 R 7 ; R 4 is H, allyl, or C1-C4 alkyl, wherein C1-C4 alkyl is optionally substituted with C1-C4 alkyl, -OR 7 , -S(0)2R 12 , -CO2R 7 , -NR 6 R 7 or -NR 9 COR 10 ; R 5 is independently selected at each occurrence from Cχ-C 6 alkyl, aryl, heterocyclyl, C1 . -C 4 haloalkyl, halo, -CN, -N0 2 , -NR 6 R 7 , -COR 7 , -OR 7 , -CONR 6 R 7 , -CON(OR 9 )R 7 , -C0 2 R 7 and -S(0) n R 13 , wherein Cι-C 6 alkyl is substituted with 0 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, -N0 2 , halo, -CN, -NR 6 R 7 , COR 7 ' -OR 7 , -CONR 6 R 7 , C0 2 R 7 and -S(0) n R 13 ; R6 and R7 are independently selected at each occurrence from H, C1-C4 alkyl, C1-C4 haloalkyl and C2-C8 alkoxyalkyl ,- wherein C1-C4 alkyl, may be substituted with 0 to 2 substituents independently selected at each occurrence from -OH or C1-C4 alkoxy groups ; R 8 , R 9 and R 10 are independently at each occurrence H or C1-C4 alkyl; R 12 and R 13 are independently at each occurrence C1-C4 alkyl or -NR 6 R 7 ; R 14 is C1-C4 alkyl or -NR 15 R 16 ; R 15 and R 1 ^ are independently at each occurrence H, C1-C4 alkyl or C2-C8 alkoxyalkyl; aryl is phenyl substituted with 0 to 3 substituents independently selected at each occurrence from C 1 -C 4 alkyl, halo, -CN, -OR 15 , -S(0) n R 14 . -COR 15 , -CO2R 15 , -NO2 and -NR 15 R 16 ; and n is independently at each occurrence 0, 1 or 2. 9. A composition of matter comprising compound of Claim 1 wherein: Z is N; Y is NR 4 , O or S(0) n ; Ar is phenyl, naphthyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, 1, 3 , 5-triazinyl, 1, 2 , 4-triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, indolinyl, pyrrolyl, oxazolyl, benzofuranyl , benzothienyl , 2,3-dihydrobenzof ranyl , 2, 3-dihydrobenzothienyl, benzothiazolyl, indazolyl, isoxazolyl or pyrazolyl, each substituted with 0 to 4 R 5 groups; wherein Ar is attached to Y through an unsaturated carbon; R 1 is H, halo, C1-C10 alkyl, C2-C10 alkenyl, C2- C10 alkynyl, C3-C8 cycloalkyl, C1-C4 haloalkyl, aryl, heterocyclyl, -CN, -OR 7 , -SH, -S(0) n R 13 , -COR 7 , -CONR 6 R 7 , -CO2R 7 , -OC(0)R 13 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , -NR 8 Cθ2R 7 , or -NR 6 R 7 , wherein C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl or C3-C8 cycloalkyl is each substituted with 0 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, -CN, -OR 7 , -SH, -S(0) n R 13 - -COR 7 , -C02R 7 , -OC(0)R 13 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , -NR 8 C02R 7 , -NR 6 R 7 , -CONR 6 R 7 , aryl and heterocyclyl; R 3 is C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C8 cycloalkyl, C1-C4 haloalkyl, aryl, heterocyclyl, -CN, -S(0)2R 13 . -CO2R 7 , -COR 7 or -CONR 6 R 7 , wherein C1.-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl or C3-C8 cycloalkyl is each substituted with 0 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, -CN, -OR 7 , -S(0) n R 13 , -COR 7 , -CO2R 7 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR β R 7 , -NR 8 C02R 7 , -NR 6 R 7 , -CONR 6 R 7 , aryl and heterocyclyl, with the proviso that when R 3 is aryl, Ar is not imidazolyl; R 4 is H, C1-C6 alkyl, C2-C6 alkenyl or C2-C6 alkynyl, wherein C2-C6 alkenyl or C2-C6 alkynyl is optionally substituted with C3 . -C4 alkyl or C3-C6 cycloalkyl and wherein C1-C6 alkyl is optionally substituted with C1-C4 alkyl, C3-C6 cycloalkyl, C3 . -C4 haloalkyl, -OR 7 , -S(0) n R 12 - -Cθ2R 7 , -NR 6 R 7 or -NR 9 COR 10 ; R 5 is independently selected at each occurrence from Cl-Cio alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C6 cycloalkyl, C4-C12 cycloalkylalkyl, aryl, heterocyclyl, halo, C1-C4 haloalkyl, -CN, -NO2, -NR 6 R 7 , -NR 8 COR 7 , -NR 8 C0 2 R 7 , -OR 7 , -COR 7 , -CO2R 7 , -CONR 6 R 7 , -CON(OR 9 )R 7 and -S(0) n R 13 , wherein Ci-Cio alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C6 cycloalkyl and C4-C12 cycloalkylalkyl are substituted with 0 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, -NO2 , halo, -CN, -OR 7 , -COR 7 , -C02R 7 , -CONR 6 R 7 , -NR 6 R 7 , -NR 8 COR 7 , -NR 8 C0 2 R 7 , -SH, and -S (0) n R 13 ; R6 and R7 are independently selected at each occurrence from H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, C4- C12 cycloalkylalkyl, aryl, aryl(Cχ-C4 alkyl)-, heterocyclyl, heterocyclyl (C1-C4 alkyl)-, morpholinoethyl, morpholinopropyl and morpholinobutyl; or NR 6 R 7 taken together as a whole is piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine or thiomorpholine; wherein C1-C4 alkyl, may be substituted with 0 to 2 substituents independently selected at each occurrence from -OH or C1-C4 alkoxy groups; R 8 is independently at each occurrence H or C1-C4 alkyl; R 9 and R 10 are independently at each occurrence selected from H, C1-C4 alkyl and C3-C6 cycloalkyl ,- R 11 is H, C1-C4 alkyl, C1-C4 haloalkyl, or C3-C6 cycloalkyl; R 12 is C1-C4 alkyl, C1-C4 haloalkyl or -NR 6 R 7 ; R 13 is C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3- C6 cycloalkyl, C4-C12 cycloalkylalkyl, -NR 6 R 7 , aryl, aryl(Cι-C4 alkyl)-, heterocyclyl or heterocyclyl (Cι~ C4 alkyl) - ; R 14 is C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, C4-C12 cycloalkylalkyl, -NR 15 R 16 ; R 15 and R f ^ are independently selected at each occurrence from H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl and C4- C12 cycloalkylalkyl; or -NR 15 R 16 taken together as a whole is piperidine, pyrrolidine, piperazine, N-methy1-piperazine, morpholine or thiomorpholine; aryl is phenyl, biphenyl or naphthyl, each substituted with 0 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, -CN, -OR 15 , -SH, -S(0) n R 14 . -COR 15 , -CO2R 15 , -0C(0)R 14 , -N02 , -NR 8 COR 15 , -N(COR 15 ) 2 , -NR 8 CONR 15 R 16 , -NR 8 C02R 15 , -NR 15 R 16 and -CONR 15 R 16 ; heterocyclyl is pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl , benzthiazolyl, isoxazolyl or pyrazolyl, each substituted with 0 to 3 substituents independently selected at each occurrence from Cι~ C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, -CN, -OR 15 , -SH, -S<0) n R 14 - -COR 15 , -CO2R 15 , -OC(0)R 14 , -N02 , -NR 8 COR 15 , -N(COR 15 ) 2 , -NR 8 CONR 15 R 16 , -NR 8 Cθ2R 15 , -NR 15 R 16 and -CONR 15 R 16 ; and n is independently at each occurrence 0 , 1 or 2. 10. A composition of matter comprising compound of Claim 9 wherein: Z is N; Y is NR 4 or 0; Ar is phenyl or pyridyl, each substituted with 0 to 4 R 5 groups; R 1 is H, halo, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, aryl, -CN, C1-C4 haloalkyl, -NR 6 R 7 , -C0NR 6 R 7 , -OR 7 , -COR 7 , -C0 2 R 7 or -S(0) n R 13 , wherein C1-C4 alkyl is substituted with 0 to 3 substituents independently selected at each occurrence from C1-C3 alkyl, C3-C6 cycloalkyl, halo, -CN, -OR 7 , -S(0) n R 13 . -COR 7 , -C02R 7 , -NR 8 COR 7 , -NR 8 C02R 7 , -NR 6 R 7 and aryl; R 3 is C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C8 cycloalkyl, C1-C4 haloalkyl, aryl, heterocyclyl, -CN, -S(0)2R 13 i -COR 7 , -CO2R 7 or -CONR 6 R 7 , wherein C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl or C3-C8 cycloalkyl is each substituted with 0 to 3 substituents independently selected at each occurrence from Cι~Ce alkyl, C 3 -C 6 cycloalkyl, C 1 -C 4 haloalkyl, halo, -CN, -OR 7 , -S(0) n R 13 , -C0 2 R 7 , -NR 8 COR 7 , -NR 8 CONR 6 R 7 , -NR 8 C0 2 R 7 , -NR 6 R 7 , aryl and heterocyclyl ; R 4 is H, C1-C6 alkyl or C2-C6 alkenyl, wherein Cχ-C6 alkyl is optionally substituted with Cχ-C4 alkyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, -OR 7 , -S(0) n R 12 , -CO2R 7 , -NR 6 R 7 or -NR 9 COR 10 ; R 5 is independently selected at each occurrence from Ci-Cβ alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C4-C8 cycloalkylalkyl, aryl, heterocyclyl, C 1 -C 4 haloalkyl, halo, -CN, -NO 2 , -NR 6 R 7 , -COR 7 , -OR 7 , -CONR 6 R 7 , -CON(OR 9 )R 7 , C0 2 R 7 and -S(0) n R 13 , wherein CI-CQ alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 - CQ cycloalkyl and C4-C8 cycloalkylalkyl are substituted with 0 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, -N0 2 , halo, -CN, -NR 6 R 7 , COR 7 ' -OR 7 , -CONR 6 R 7 , C0 2 R 7 and -S ( 0 ) n R 13 ; R.6 and R7 are independently selected at each occurrence from H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, C4- Cχ2 cycloalkylalkyl, aryl, aryl(Cχ-C4 alkyl)-, heterocyclyl , heterocyclyl (Cx-C4 alkyl ) - , morpholinoethyl, morpholinopropyl and morpholinobutyl ,- or -NR 6 R 7 taken together as a whole is piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine or thiomorpholine; wherein C1-C4 alkyl, may be substituted with 0 to 2 substituents independently selected at each occurrence from -OH or C1-C4 alkoxy groups ; R 8 is independently at each occurrence H or C1-C4 alkyl; R 9 and R 10 are independently at each occurrence selected from H, C1-C4 alkyl and C3-C6 cycloalkyl; R 11 is H, C1-C4 alkyl, Cχ-C4 haloalkyl, or C3-C6 cycloalkyl; R 12 is C1-C4 alkyl, Cχ-C4 haloalkyl or -NR 6 R 7 ; R 13 is Cχ-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3- C6 cycloalkyl, C4-CX2 cycloalkylalkyl, -NR 6 R 7 , aryl, aryl(Cχ-C4 alkyl)-, heterocyclyl or heterocyclyl (Cχ~ C4 alkyl)-; R 14 is Cχ-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, C4-C12 cycloalkylalkyl, -NR 15 R 16 ; R 15 and R ^ are independently selected at each occurrence from H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl and C4- Cχ2 cycloalkylalkyl; or -NR 15 R 16 taken together as a whole is piperidine, pyrrolidine, piperazine, N-methyl-piperazine, morpholine or thiomorpholine; aryl is phenyl substituted with 0 to 3 substituents independently selected at each occurrence from C 1 -C 4 alkyl, halo, -CN, -OR 15 , -S(0) n R 14 - -COR 15 , -C02R 15 , -Nθ2, -NR 8 COR 15 , -NR 8 CONR 15 R 16 , -NR 8 C02R 15 and -NR 15 R 16 ; heterocyclyl is pyridyl, pyrimidinyl, triazinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl or pyrazolyl, each substituted with 0 to 3 substituents independently selected at each occurrence from C 1 -C 4 alkyl, halo, -CN, -OR 15 , -S(0) n R 14 - -C02R 15 , -N02, -NR 8 COR 15 , -NR 8 CONR 15 R 16 , -NR 8 C02R 15 , and -NR 15 R 16 ; and n is independently at each occurrence 0, 1 or 2. 11. A composition of matter comprising compound of Claim 10 wherein: Z is N; Y is NR 4 ; Ar is phenyl or pyridyl, each substituted with 0 to 4 R 5 groups ; R 1 is H, halo, C 1 -C 4 alkyl, Cχ-C3 haloalkyl, cyclopropyl, -CN, -NR 6 R 7 , -CONR 6 R 7 , -COR 7 , -C0 2 R 7 , -OR 7 or -S(0) n R 13 wherein C1-C4 alkyl is substituted with 0 to 3 substituents independently selected at each occurrence from C3-C4 cycloalkyl, halo, -CN, -OR 7 , -S(0) n R 13 , -COR 7 , -C02R 7 , -NR 6 R 7 ; R 3 is Cχ-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, Cχ-C4 haloalkyl or aryl, wherein Cχ-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or C3-C6 cycloalkyl is each substituted with 0 to 3 substituents independently selected at each occurrence from C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C1-C 4 haloalkyl, halo, -CN, -OR 7 , -S(0) n R 13 , -C0 2 R 7 , -NR 8 C0R 7 , -NR 8 CONR 6 R 7 , -NR 8 C0 2 R 7 , -NR 6 R 7 and aryl; R 4 is H, allyl, or C1-C4 alkyl, wherein C1-C4 alkyl is optionally substituted with C1-C4 alkyl, -OR 7 , -S(0)2R 12 . -C02R 7 , -NR 6 R 7 or -NR 9 COR 10 ; R 5 is independently selected at each occurrence from Ci-Cβ alkyl, aryl, heterocyclyl, C 1 -C 4 haloalkyl, halo, -CN, -N0 , -NR 6 R 7 , -COR 7 , -OR 7 , -CONR 6 R 7 , -CON(OR 9 )R 7 , -C0 2 R 7 and -S(0) n R 13 , wherein Ci-Cβ alkyl is substituted with 0 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, -N0 2 , halo, -CN, -NR 6 R 7 , COR 7 - -OR 7 , -CONR 6 R 7 , C0 2 R 7 and -S(0) n R 13 ; R 6 and R7 are independently selected at each occurrence from H, C1-C4 alkyl, C1-C4 haloalkyl and C2-C8 alkoxyalkyl ; wherein C1-C4 alkyl, may be substituted with 0 to 2 substituents independently selected at each occurrence from -OH or Cχ-C4 alkoxy groups; R 8 , R 9 and R 10 are independently at each occurrence H or C1-C4 alkyl; R 12 and R 13 are independently at each occurrence C1-C4 alkyl or -NR 6 R 7 ; R 14 is Cχ-C4 alkyl or -NR 15 R 16 ; R 15 and R ( 5 are independently at each occurrence H, C1-C4 alkyl or C2-C8 alkoxyalkyl; aryl is phenyl substituted with 0 to 3 substituents independently selected at each occurrence from C 1 -C 4 alkyl, halo, -CN, -OR 15 , -S(0) n R 14 . -COR 15 , -C02R 15 , -NO2 and -NR 15 R 16 ; and n is independently at each occurrence 0 , 1 or 2. 12. A composition of matter comprising compound of Claim 11 wherein: Z is N; Y is NR 4 ; Ar is phenyl or pyridyl, each substituted with 2 to 4 R 5 groups ; R 1 is H, methyl, ethyl, cyclopropyl, -CF 3 , or -N(CH 3 ) ; R 3 is Cχ-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C4 haloalkyl or aryl, wherein Cχ-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or C3-C6 cycloalkyl is each substituted with 0 to 3 substituents independently selected at each occurrence from C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, -CF 3 , halo, -CN, -OR 7 , and aryl; R 4 is H, methyl, ethyl, i-propyl, n-propyl, n-butyl, i-butyl, s-butyl, n-butyl, or allyl; R 5 is independently selected at each occurrence from methyl, ethyl, i-propyl, n-propyl, aryl, -CF 3 , halo, -CN, -N(CH 3 ) 2 , -C(=0)CH 3 , -OCH 3 , -OCH 2 CH 3 , -OCF 3 , and -S(0) 2 CH 3 ; R 14 is C1-C4 alkyl or -NR 15 R 16 ; R 15 and R 16 are independently at each occurrence H, C1-C4 alkyl or C2-C8 alkoxyalkyl; aryl is phenyl substituted with 0 to 3 substituents independently selected at each occurrence from C 1 -C 4 alkyl, halo, -CN, -OR 15 , -S(0) n R 14 . -COR 15 , -CO2R 15 , -NO2 and -NR 15 R 16 ; and n is independently at each occurrence 0, 1 or 2. 13. A composition of matter comprising compound of Claim 9 wherein: Z is N; Y is NR 4 or O; Ar is phenyl or pyridyl, each substituted with 0 to 4 R 5 groups ; R 1 is H, halo, Cχ-Cχo alkyl, C2-Cχo alkenyl, C2~ Cχo alkynyl, C3-C8 cycloalkyl, C1-C4 haloalkyl, aryl, heterocyclyl, -CN, -OR 7 , -SH, -S(0) n R 13 . -COR 7 , -CONR 6 R 7 , -C02R 7 , -OC(0)R 13 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , -NR 8 C02R 7 , or -NR 6 R 7 , wherein Cχ-Cχo alkyl, C2~Cχo alkenyl, C2-Cχo alkynyl or C3-C8 cycloalkyl is each substituted with 0 to 3 substituents independently selected at each occurrence from Cχ-Cβ alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, -CN, -OR 7 , -SH, -S(0) n R 13 , -COR 7 , -CO2R 7 , -OC(0)R 13 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , -NR 8 C02R 7 , -NR 6 R 7 , -CONR 6 R 7 , aryl and heterocyclyl; R 3 is C 1 -C 4 alkyl, -CN, C3-C6 cycloalkyl, C 1 -C 4 haloalkyl, -OR 7 , -COR 7 , -C0 2 R 7 or -CONR 6 R 7 , wherein C1-C4 alkyl is substituted with 0 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, halo, -CN, -OR 7 , -S(0) n R 13 . -COR 7 , -CO2R 7 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , -NR 8 Cθ2R 7 , -NR 6 R 7 and -CONR 6 R 7 ; R 4 is H, Cχ-C6 alkyl or C2-C6 alkenyl, wherein Cχ-C6 alkyl is optionally substituted with C1-C4 alkyl, C3-C6 cycloalkyl, Cχ-C4 haloalkyl, -OR 7 , -S(0) n R 12 , -CO2R 7 , -NR 6 R 7 or -NR 9 COR 10 ; R 5 is independently selected at each occurrence from Cl-Cio alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C6 cycloalkyl, C4-CX2 cycloalkylalkyl, aryl, heterocyclyl, -Nθ2, halo, -CN, C1-C4 haloalkyl, -NR 6 R 7 , -NR 8 COR 7 , -NR 8 C0 2 R 7 , -OR 7 , -COR 7 , -C02R 7 , -CONR 6 R 7 , -CON(OR 9 )R 7 and -S(0) n R 13 . wherein Cχ-Cχo alkyl, C2~Cχo alkenyl, C2-C10 alkynyl, C3-C6 cycloalkyl and C4-CX2 cycloalkylalkyl are substituted with 0 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, -NO2 , halo, -CN, -OR 7 , -COR 7 , -CO2R 7 , -CONR 6 R 7 , -NR 6 R 7 , -NR 8 COR 7 , -NR 8 C0 2 R 7 and -S(0) n R 13 ; R^ and R7 are independently selected at each occurrence from H, C1-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, C4- Cl2 cycloalkylalkyl, aryl, aryl(Cχ-C4 alkyl)-, heterocyclyl, heterocyclyl (Cχ-C4 alkyl)-, morpholinoethyl, morpholinopropyl and morpholinobutyl; or NR 6 R 7 taken together as a whole is piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine or thiomorpholine; wherein Cχ-C4 alkyl, may be substituted with 0 to 2 substituents independently selected at each occurrence from -OH or C1-C4 alkoxy groups; R 8 is independently at each occurrence H or C1-C4 alkyl; R 9 and R 1 ^ are independently at each occurrence selected from H, C1-C4 alkyl and C3-C6 cycloalkyl; R 11 is H, C1-C4 alkyl, Cχ-C4 haloalkyl, or C3-C6 cycloalkyl; R 12 is C1-C4 alkyl, Cχ-C4 haloalkyl or -NR 6 R 7 ; R 13 is Cχ-C4 alkyl, C1-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, C4-CX2 cycloalkylalkyl, -NR 6 R 7 , aryl, aryl(Cχ-C4 alkyl)-, heterocyclyl or heterocyclyl (Cχ-C4 alkyl)-; R 14 is C1-C4 alkyl, Cχ-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, C4-CX2 cycloalkylalkyl, -NR 15 R 16 ; R 15 and R 1 ^ are independently selected at each occurrence from H, C1-C4 alkyl, Cχ-C4 haloalkyl, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl and C4- Cχ2 cycloalkylalkyl; or -NR 1 R lf ^ taken together as a whole is piperidine, pyrrolidine, piperazine, N-methyl-piperazine, morpholine or thiomorpholine; aryl is phenyl or naphthyl, each substituted with 0 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, halo, -CN, -OR 15 , -S(0) n R 14 , -COR 15 , -C02R 15 , -N02 , -NR 8 COR 15 , -NR 8 CONR 15 R 16 , -NR 8 C02R 15 and -NR 15 R 16 ; heterocyclyl is pyridyl, pyrimidinyl, triazinyl, furanyl, thienyl, imidazolyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl or pyrazolyl, each substituted with 0 to 3 substituents independently selected at each occurrence from C 1 -C 4 alkyl, halo, -CN, -OR 15 , -S(0) n R 14 , -C02R 15 , -N02 , -NR 8 COR 15 , -NR 8 CONR 15 R 16 , -NR 8 C02R 15 , and -NR 15 R 16 ; and n is independently at each occurrence 0, 1 or 2. 14. A composition of matter comprising compound of Claim 13 wherein: Z is N; Y is NR 4 ; Ar is phenyl or pyridyl, each substituted with 0 to 4 R 5 groups ; R 1 is H, halo, Cχ-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, aryl, heterocyclyl, -CN, -OR 7 , -S(0) n R 13 - -COR 7 , -CONR 6 R 7 , -CO2R 7 or -NR 6 R 7 , wherein Cχ-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or C3-C6 cycloalkyl is each substituted with 0 to 3 substituents independently selected at each occurrence from Cχ-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, -CN, -OR 7 , -SH, -S(0) n R 13 , -COR 7 , -C02R 7 , -OC(0)R 13 , -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , -NR 8 C02R 7 , -NR 6 R 7 , -CONR 6 R 7 , aryl and heterocyclyl; R 3 is C 1 -C 4 alkyl, -CN, C3-C6 cycloalkyl, C 1 -C 4 haloalkyl, -OR 7 , -COR 7 or -C0 2 R 7 , wherein C1-C4 alkyl is substituted with 0 to 3 substituents independently selected at each occurrence from C3-C6 cycloalkyl, C1-C4 haloalkyl, halo, -CN, -OR 7 , -S(0) n R 13 , -COR 7 , -CO2R 7 , -NR 8 COR 7 , -NR 6 R 7 and -CONR 6 R 7 ; R 4 is H, allyl, or C1-C4 alkyl, wherein C1-C4 alkyl is optionally substituted with C1-C4 alkyl, -OR 7 , -S(0)2R 12 - -C02R 7 , -NR 6 R 7 or -NR 9 COR 10 ; R 5 is independently selected at each occurrence from Ci-Cβ alkyl, aryl, heterocyclyl, C 1 -C 4 haloalkyl, halo, -CN, -N0 2 , -NR 6 R 7 , -COR 7 , -OR 7 , -CONR 6 R 7 , -CON(OR 9 )R 7 , -C0 2 R 7 and -S(0) n R 13 , wherein Ci-Cβ alkyl is substituted with 0 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, -N0 2 , halo, -CN, -NR 6 R 7 , COR 7 - -OR 7 , -CONR 6 R 7 , C0 2 R 7 and -S(0) n R 13 ; R6 and R7 are independently selected at each occurrence from H, C1-C4 alkyl, C1-C4 haloalkyl and C2-C8 alkoxyalkyl ; wherein Cχ-C4 alkyl, may be substituted with 0 to 2 substituents independently selected at each occurrence from -OH or C1-C4 alkoxy groups; R 8 , R 9 and R 10 are independently at each occurrence H or C1-C4 alkyl; R 12 and R 13 are independently at each occurrence C1-C4 alkyl or -NR 6 R 7 ; R 14 is C1-C4 alkyl or -NR 15 R 16 ; R 15 and R lf are independently at each occurrence H, C1-C4 alkyl or C2-C8 alkoxyalkyl; aryl is phenyl substituted with 0 to 3 substituents independently selected at each occurrence from C 1 -C 4 alkyl, halo, -CN, -OR 15 , -S(0) n R 14 - -COR 15 , -CO2R 15 , -NO2 and -NR 15 R 16 ; and n is independently at each occurrence 0, 1 or 2. 15. A method for treating affective disorders, anxiety, depression, post-traumatic stress disorders, supranuclear palsy, seizure disorders, stroke, irritable bowel syndrome, immune suppression, Alzheimer's disease, gastrointestinal disease, anorexia nervosa or other eating disorders, drug or alcohol withdrawal symptoms, drug addiction, inflammatory disorders, or fertility problems in a mammal in need of such treatment comprising administering to the mammal a therapeutically effective amount of a compound of formula (I) as defined in any one of Claims 1-14. 16. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of formula (I) as defined in any one of Claims 1-14.

Inventors: ARNOLD CHARLES R III, ARVANITIS ARGYRIOS GEORGIOS, FRIETZE WILLIAM E, OLSON RICHARD ERIC, ARNOLD, CHARLES, R., III, ARVANITIS, ARGYRIOS, GEORGIOS, FRIETZE, WILLIAM, E., OLSON, RICHARD, ERIC
Applicants: DU PONT MERCK PHARMA, THE DU PONT MERCK PHARMACEUTICAL COMPANY
Application year: 1997
Main classification: C07D241
IPC codes: A61K31, A61P25, C07D241, C07D253, C07D401, C07D405