AZOLO TRIAZINES AND PYRIMIDINES

Abstract: Corticotropin releasing factor (CRF) antagonists of formula (I) or (II) and their use in treating anxiety, depression, and other psychiatric, neurological disorders as well as treatment of immunological, cardiovascular or heart-related diseases and colonic hypersensitivity associated with psychopathological disturbance and stress.

Description: TITLE AZOLO TRIAZINES AND PYRIMIDINES FIELD OF THE INVENTION This invention relates a treatment of psychiatric disorders and neurological diseases including major depression, anxiety-related disorders, post-traumatic stress disorder, supranuclear palsy and feeding disorders as well as treatment of immunological, cardiovascular or heartrelated diseases and colonic hypersensitivity associated with psychopathological disturbance and stress, by administration of certain [1,5-a3- pyrazolo-1,3,5-triazines, [1,5-a]-1,2,3-triazolo1,3,5-triazines, [1,5-a]-pyrazolo-pyrimidines and [1,5-a] -1,2, 3-triazolo-pyrimidines. BACKGROUND OF THE INVENTION Corticotropin releasing factor (herein referred to as CRF), a 41 amino acid peptide, is the primary physiological regulator of proopiomelanocortin(POMC) -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. Horm. Res. 39:245 (1983); G.F. Koob, Persp. Behav. Med. 2:39 (1985); E.B. De Souza et al., J. Neurosci. 5:3189 (1985)1. 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 feeding 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); C.M. 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. Hoisboer 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 CKF 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 / nonbenzodiazepine 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 Horm. 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., Psychopharmacology 86:170 (1985); K.T. Britton et al., Psychopharmacology 94:306 (1988)] and in the acoustic startle test [N.R. Swerdlow et al., Psychopharmacology 88:147 (1986)] in rats. The benzodiazepine receptor antagonist (Ro15-1788), 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 CRF941) 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)]. Several publications describe corticotropin releasing factor antagonist compounds and their use to treat psychiatric disorders and neurological diseases. Examples of such publications include DuPont Merck PCT application US94/11050 , Pfizer WO 95/33750, Pfizer WO 95/34563, Pfizer WO 95/33727 and Pfizer EP 0778 277 Al. Insofar as is known, [1,5-a]-pyrazolo- 1,3,5-triazines, [1,5-a]-1,2,3-triazolo-1,3,5- triazines, [1,5-a]-pyrazolo-pyrimidines and [1,5-a] l,2,3-triazolo-pyrimidines, have not been previously reported as corticotropin releasing factor antagonist compounds useful in the treatment of psychiatric disorders and neurological diseases. However, there have been publications which teach some of these compounds for other uses. For instance, EP 0 269 859 (Ostuka, 1988) discloses pyrazolotriazine compounds of the formula EMI5.1 where R1 is OH or alkanoyl, R2 is H, OH, or SH, and R3 is an unsaturated heterocyclic group, naphthyl or substituted phenyl, and states that the compounds have xanthine oxidase inhibitory activity and are useful for treatment of gout. EP 0 594 149 (Ostuka, 1994) discloses pyrazolotriazine and pyrazolopyrimidine compounds of the formula EMI5.2 where A is CH or N, R0 and R3 are H or alkyl, and R1 and R2 are H, alkyl, alkoxyl, alkylthio, nitro, etc., and states that the compounds inhibit androgen and are useful in treatment of benign prostatic hypertrophy and prostatic carcinoma. US 3,910,907 (ICI, 1975) discloses pyrazolotriazines of the formula: EMI6.1 where R1 is CH3, C2H5 or C6H5, X is H, C6H5, m-CH3C6H4, CN, COOEt, Cl, I or Br, Y is H, C6H5, o-CH3C6H4, or p CH3C6H4, and Z is OH, H, CH3, C2H5, C6H5, n-C3H7, i-C3H7, SH, SCH3, NHC4Hg, or N(C2Hs)2, and states that the compounds are c-AMP phosphodiesterase inhibitors useful as bronchodilators. US 3,995,039 discloses pyrazolotriazines of the formula: EMI6.2 where R1 is H or alkyl, R2 is H or alkyl, R3 is H, alkyl, alkanoyl, carbamoyl, or lower alkylcarbamoyl, and R is pyridyl, pyrimidinyl, or pyrazinyl, and states that the compounds are useful as bronchodilators. US 5,137,887 discloses pyrazolotriazines of the formula EMI7.1 where R is lower alkoxy, and teaches that the compounds are xanthine oxidase inhibitors and are useful for treatment of gout. US 4,892,576 discloses pyrazolotriazines of the formula EMI7.2 where X is O or S, Ar is a phenyl, naphthyl, pyridyl or thienyl group, R6-Rg are H, alkyl, etc., and R9 is H, alkyl, phenyl, etc. The patent states that the compounds are useful as herbicides and plant growth regulants. US 5,484,760 and WO 92/10098 discloses herbicidal compositions containing, among other things, a herbicidal compound of the formula EMI8.1 where A can be N, B can be CR3, R3 can be phenyl or substituted phenyl, etc., R is -N(R4)So2Rs or -SO2N(R6)R7 and R1 and R2 can be taken together to form EMI8.2 where X, Y and Z are H, alkyl, acyl, etc. and D is O or S. US 3,910,907 and Senga et al., J. Med. Chem., 1982, 25, 243-249, disclose triazolotriazines cAMP phosphodiesterase inhibitors of the formula EMI8.3 where Z is H, OH, CH3, C2Hs, C6Hs, n-C3H7, iso-C3H7, SH, SUCH3, NH(n-C4H9), or N(C2H5)2, R is H or CH3, and R1 is CH3 or C2Hs. The reference lists eight therapeutic areas where inhibitors of cAMP phosphodiesterase could have utility: asthma, diabetes mellitus, female fertility control, male infertility, psoriasis, thrombosis, anxiety, and hypertension. W095/35298 (Otsuka, 1995) discloses pyrazolopyrimidines and states that they are useful as analgesics. The compounds are represented by the formula EMI9.1 where Q is carbonyl or sulfonyl, n is O or 1, A is a single bond, alkylene or alkenylene, R1 is H, alkyl, etc., R2 is naphthyl, cycloalkyl, heteroaryl, substituted phenyl or phenoxy, R is H, alkyl or phenyl, R4 is H, alkyl, alkoxycarbonyl, phenylalkyl, optionally phenylthio-substituted phenyl, or halogen, R5 and R6 are H or alkyl. EP 0 591 528 (Otsuka,1991) discloses antiinflammatory use of pyrazolopyrimidines represented by the formula EMI9.2 where R1, R2, R3 and R4 are H, carboxyl, alkoxycarbonyl, optionally substituted alkyl, cycloalkyl, or phenyl, K5 is SR6 or NR7Rg, K6 is pyridyl or optionally substituted phenyl, and R7 and R8 are H or optionally substituted phenyl. Springer et al, J. Med. Chem., 1976, vol. 19, no. 2, 291-296 and Springer U.S. patents 4021,556 and 3,920,652 disclose pyrazolopyrimidines of the formula EMI10.1 where R can be phenyl, substituted phenyl or pyridyl, and their use to treat gout, based on their ability to inhibit xanthine oxidase. Joshi et al., J. Prakt. Chemie, 321, 2, 1979, 341-344, discloses compounds of the formula EMI10.2 where R1 is CF3, C2F5, or C6H4F, and R2 is CH3, C2H5, CF3, or C6H4F. Maquestiau et al., Bull. Soc. Belg., vol.101, no. 2, 1992, pages 131-136 discloses a pyrazolof1,5- a]pyrimidine of the formula EMI11.1 Ibrahim et al., Arch. Pharm. (weinheim) 320, 487-491 (1987) discloses pyrazolo[1,5-ajpyrimidines of the formula EMI11.2 where R is NH2 or OH and Ar is 4-phenyl-3-cyano-2aminopyrid-2-yl. Other references which disclose azolopyrimidines inclued EP 0 511 528 (Otsuka, 1992), US 4,997,940 (Dow, 1991), EP 0 374 448 (Nissan, 1990), US 4,621,556 (ICN,1997), EP 0 531 901 (Fujisawa, 1993), US 4,567,263 (BASF, 1986), EP 0 662 477 (Isagro, 1995), DE 4 243 279 (Bayer, 1994), US 5,397,774 (Upjohn, 1995), EP 0 521 622 (Upjohn, 1993), WO 94/109017 (Upjohn, 1994), J. Med. Chem., 24, 610-613 (1981), and J. Het. Chem., 22, 601 (1985). SUMMARY OF THE INVENTION In accordance with one aspect, the present invention provides novel compounds, pharmaceutical compositions and methods which may be used in the treatment of affective disorder, anxiety, depression, irritable bowel syndrome, post-traumatic stress disorder, supranuclear palsy, immune suppress ion, ALheimer's disease, gastrointestinal disease, anorexia nervosa or other feeding disorder, drug or alcohol withdrawal symptoms, drug addiction, inflammatory disorder, fertility problems, disorders, the treatment of which can be effected or facilitated by antagonizing CRF, including but not limited to disorders induced or facilitated by CRF, or a disorder selected from inflammatory disorders such as rheumatoid arthritis and osteoarthritis, pain, asthma, psoriasis and allergies; generalized anxiety disorder; panic, phobias, obsessive-compulsive disorder; post-traumatic stress disorder; sleep disorders induced by stress; pain perception such as fibromyalgia; mood disorders such as depression, including major depression, single episode depression, recurrent depression, child abuse induced depression, and postpartum depression; dysthemia; bipolar disorders; cyclothymia; fatigue syndrome; stress-induced headache; cancer, human immunodeficiency virus (HIV) infections; neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and Huntington's disease; gastrointestinal diseases such as ulcers, irritable bowel syndrome, Crohn's disease, spastic colon, diarrhea, and post operative ilius and colonic hypersensitivity associated by psychopathological disturbances or stress; eating disorders such as anorexia and bulimia nervosa; hemorrhagic stress; stress-induced psychotic episodes; euthyroid sick syndrome; syndrome of inappropriate antidiarrhetic hormone (ADH); obesity; infertility; head traumas; spinal cord trauma; ischemic neuronal damage (e.a., cerebral ischemia such as cerebral hippocampal ischemia); excitotoxic neuronal damage; epilepsy; cardiovascular and hear related disorders including hypertension, tachycardia and congestive heart failure; stroke; immune dysfunctions including stress induced immune dysfunctions (e.a., stress induced fevers, porcine stress syndrome, bovine shipping fever, equine paroxysmal fibrillation, and dysfunctions induced by confinement in chickens, sheering stress in sheep or human-animal interaction related stress in dogs); muscular spasms; urinary incontinence; senile dementia of the Alzheimer's type; multiinfarct dementia; amyotrophic lateral sclerosis; chemical dependencies and addictions (e.a., dependencies on alcohol, cocaine, heroin, benzodiazepines, or other drugs); drug and alcohol withdrawal symptoms; osteoporosis; psychosocial dwarfism and hypoglycemia in a mammal. The present invention provides novel compounds which bind to corticotropin releasing factor receptors, thereby altering the anxiogenic effects of CKF secretion. The compounds of the present invention are useful for the treatment of psychiatric disorders and neurological diseases, anxiety-related disorders, post-traumatic stress disorder, supranuclear palsy and feeding disorders as well as treatment of immunological, cardiovascular or heartrelated diseases and colonic hypersensitivity associated with psychopathological disturbance and stress in a mammal. According to another aspect, the present invention provides novel compounds of Formulae (1) and (2) (described below) which are useful as antagonists of the corticotropin releasing factor. The compounds of the present invention exhibit activity as corticotropin releasing factor antagonists and appear to suppress CKF hypersecretion. The present invention also includes phArmaceutical compositions containing such compounds of Formulae (1) and (2), and methods of using such compounds for the suppression of CRF hypersecretion, and/or for the treatment of anxiogenic disorders. According to yet another aspect of the invention, the compounds provided by this invention (and especially labelled compounds of this invention) are also useful as standards and reagents in determining the ability 4f a potential pharmaceutical to bind to the CRF receptor. DETAILED DESCRIPTION OF INVENTION [1] The present invention comprises a method of treating affective disorder, anxiety, depression, headache, irritable bowel syndrome, post-traumatic stress disorder, supranuclear palsy, immune suppression, Alzheimer's disease, gastrointestinal diseases, anorexia nervosa or other feeding disorder, drug addiction, drug or alcohol withdrawal symptoms, inflammatory diseases, cardiovascular or heartrelated diseases, fertility problems, human immunodeficiency virus infections, hemorrhagic stress, obesity, infertility, head and spinal cord traumas, epilepsy, stroke, ulcers, amyotrophic lateral sclerosis, hypoglycemia or a disorder the treatment of which can be effected or facilitated by antagonizing CRF, including but not limited to disorders induced or facilitated by CRF, in mammals comprising administering to the mammal a therapeutically effective amount of a compound of Formulae (1) or (2): EMI15.1 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereolsomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof, wherein: A is N or CR; Z is N or CR2; Ar is selected from phenyl, naphthyl, pyridyl, pyrimidinyl, triazinyl, furanyl, thienyl, benzothienyl, benzofuranyl, 2,3 dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, indanyl, 1,2-benzopyranyl, 3,4-dihydro-1,2 benzopyranyl, tetralinyl, each Ar optionally substituted with 1 to 5 R4 groups and each Ar is attached to an unsaturated carbon atom; R is independently selected at each occurrence from H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, halo, CN, C1-C4 haloalkyl; R1 is independently selected at each occurrence from H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, halo, CN, C1-C4 haloalkyl, C1-C12 hydroxyalkyl, C2-C12 alkoxyalkyl, C2-Clo cyanoalkyl, C3-C6 cycloalkyl, C4-C10 cycloalkylalkyl, NR9R10, C1 C4 alkyl-NR9R10, NR9COR10, OR11, SH or S(O)nR12; R2 is selected from H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl, C4-C10 cycloalkylalkyl, C1-C4 hydroxyalkyl, halo, CN, -NR6R7, NR9COR10, -NR6S(O)nR7, S(O)nNR6R7, C1 C4 haloalkyl, -OR7, SH or -S(O)nR12; R3 is selected from: -H, OR7, SH, S(O)nR13, COR7, CO2R7, OC(O)R13, NR8COR7, N(COR7)2, NR8CONR6R7, NR8Co2R13, NR6R7, NR6aR7a1 N(OR7)R6, CONR6R7, aryl, heteroaryl and heterocyclyl, or -C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-Cg cycloalkyl, C5-Cg cycloalkenyl, C4- C12 cycloalkylalkyl or C6-C10 cycloalkenylalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl and heterocyclyl; R4 is independently selected at each occurrence from: C1-Clo alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C6 cycloalkyl, C4-C12 cycloalkylalkyl, N02, halo, CN, C1-C4 haloalkyl, NR6R7, NR8COR7, NR8CO2R7, COR7, OR7, CONR6R7, CO(NOR9)R7, CO2R7, or S(O)nR7, where each such C1-C10 alkyl, C2 C10 alkenyl, C2-C10 alkynyl, C3-C6 cycloalkyl and C4-C12 cycloalkylalkyl are optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, NO2, halo, CN, NR6R7, NR8COR7, NR8CO2R7, COR7 OR7, CONR6R7, CO2R7, CO(NOR9)R7, or S(O)nR7; R6 and R7, R6a and R7a are independently selected at each occurrence from: -H, -C1-C10 alkyl, C3-C10 alkenyl, C3-C10 alkynyl, C1-C10 haloalkyl with 1-10 halogens, C2-Cg alkoxyalkyl, C3-C6 cycloalkyl, 04- C12 cycloalkylalkyl, C5-C10 cycloalkenyl, or C6-C14 cycloalkenylalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, 03- C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl, -aryl, aryl(C1-C4 alkyl), heteroaryl, heteroaryl(C1-C4 alkyl), heterocyclyl or heterocyclyl(C1-C4 alkyl); alternatively, NR6R7 and NR6aR7a are independently piperidine, pyrrolidine, piperazine, Nmethylpiperazine, morpholine or thiomorpholine, each optionally substituted with 1-3 C1-C4 alkyl groups; R8 is independently selected at each occurrence from H or C1-C4 alkyl; R and R10 are independently selected at each occurrence from H, C1-C4 alkyl, or C3-C6 cycloalkyl; K11 is selected from H, C1-Cq alkyl, C1-C4 haloalkyl, or C3-C6 cycloalkyl; R12 is C1-C4 alkyl or C1-C4 haloalkyl; R13 is selected from C1-q alkyl, C1-C4 haloalkyl, C2-Cg alkoxyalkyl, C3-C6 cycloalkyl, 04- C12 cycloalkylalkyl, aryl, aryl(C1-C4 alkyl)-, heteroaryl or heteroaryl(C1-C4 alkyl)-; R14 is selected from C1-C10 alkyl, C3-C10 alkenyl, 03- C10 alkynyl, C3-Cg cycloalkyl, or 04- C12 cycloalkylalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, 03- C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR15, COR15, CO2R15, OC(O)R15, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R15, NR16R15, CONR16R15, and C1-C6 alkylthio, C1-C6 alkylsulfinyl and C1-C6 alkylsulfonyl; R15 and R16 are independently selected at each occurrence from H, C1-C6 alkyl, C3-C10 cycloalkyl, C4-016 cycloalkylalkyl, except that for S(O)nR15, R15 cannot be H; aryl is phenyl or naphthyl, each optionally substituted with 1 to 5 substituents independently selected at each occurrence from C1-C6 alkyl, C3 C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR15, COR15, CO2R15, OC(O)R15, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R15, NR16R151 and CONR16R15; heteroaryl is pyridyl, pyrimidinyl, triazinyl, furanyl, pyranyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, isoxazolyl, pyrazolyl, 2,3 dihydrobenzothienyl or 2,3-dihydrobenzofuranyl, each being optionally substituted with 1 to 5 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR15, -00K15, C02R15, O0(O)K15, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R15, NR16R15, and CONR16R15; heterocyclyl is saturated or partially saturated heteroaryl, optionally substituted with 1 to 5 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR15, COR15, CO2R15, OC(O)R15, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R15, NR15R16, and 00NK16K15; n is independently at each occurrence 0, 1 or 2, [2] Preferred methods of the present invention are methods in wherein in the compound of Formulae (1) or (2), Ar is phenyl, pyridyl or 2,3dihydrobenzofuranyl, each optionally substituted with 1 to 4 R4 substituents. [; Further preferred methods of the above invention are methods wherein, in the compound of Formulae (1) or (2), A is N, Z is CR2, Ar is 2,4-dichlorophenyl, 2,4-dimethylphenyl or 2,4,6-trimethylphenyl, R1 and R2 are CH3, and R3 is NR6aR7a. [4] The present invention comprises compounds of Formulae (1) or (2): EMI20.1 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein: A is N or CR; Z is N or CR2; Ar is selected from phenyl, naphthyl, pyridyl, pyrimidinyl, triazinyl, furanyl, thienyl, benzothienyl, benzofuranyl, 2,3 dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, indanyl, 1,2-benzopyranyl, 3,4-dihydro-1,2 benzopyranyl, tetralinyl, each Ar optionally substituted with 1 to 5 R4 groups and each Ar is attached to an unsaturated carbon atom; R is independently selected at each occurrence from H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, halo, CN, C1-C4 haloalkyl; R1 is independently selected at each occurrence from H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, halo, CN, C1-C4 haloalkyl, C1-C12 hydroxyalkyl, C2-C12 alkoxyalkyl, C2-C10 cyanoalkyl, C3-C6 cycloalkyl, C4-C10 cycloalkylalkyl, NR9R10, C1 C4 alkyl-NR9R10, NR9CoR10, OR11, SH or S(O)nR12; R2 is selected from H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl, C4-C10 cycloalkylalkyl, C1-C4 hydroxyalkyl, halo, CN, -NR6R7, NR9COR10, -NR6S(O)nR7, S(O)nNR6R7, C1 C4 haloalkyl, -OR7, SH or -S(O)nR12; R3 is selected from: -H, OR7, SH, S(O)nR13, COR7, CO2R7, OC(O)R13, NR8COR7, N(COR7)2, NR8CONR6R7, NR8CO2R13, NR6R7, NR6aR7a, N(OR7)R6, CONR6R7, aryl, heteroaryl and heterocyclyl, or -C1-Clo alkyl, C2-C10 alkenyl, C2-C1o alkynyl, C3-C8 cycloalkyl, C5-C8 cycloalkenyl, C4 C12 cycloalkylalkyl or C6-C10 cycloalkenylalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, C02R15, OC (O) R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl and heterocyclyl; R4 is independently selected at each occurrence from: C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C6 cycloalkyl, C4-C12 cycloalkylalkyl, N02, halo, CN, C1-C4 haloalkyl, NR6R7, NR8COR7, NR8CO2R7, COR7, OR7, CONR6R7, CO(NOR9)R7, CO2R7, or S(O)nR7, where each such C1-C10 alkyl, 02- C10 alkenyl, C2-C10 alkynyl, C3-C6 cycloalkyl and C4-C12 cycloalkylalkyl are optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, NO2, halo, CN, NR6R7, NR8COR7, NR8CO2R7, COR7 OR7, CONR6R7, CO2R7, CO(NOR9)R7, or S(O)nR7; R6 and R7, R6a and R7a are independently selected at each occurrence from: -H, -C1-C10 alkyl, C3-C10 alkenyl, C3-C10 alkynyl, C1-C10 haloalkyl with 1-10 halogens, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, 04- C12 cycloalkylalkyl, C5-C10 cycloalkenyl, or C6-C14 cycloalkenylalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, 03- C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl, -aryl, aryl(C1-C4 alkyl), heteroaryl, heteroaryl(C1-C4 alkyl), heterocyclyl or heterocyclyl(C1-C4 alkyl), alternatively, NR6R7 and NR6aR7a are independently piperidine, pyrrolidine, piperazine; Nmethylpiperazine, morpholine or thiomorpholine, each optionally substituted with 1-3 C1-C4 alkyl groups; R8 is independently selected at each occurrence from H or C1-C4 alkyl; R9 at each occurrence from C1-C6 alkyl, 03- C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR15, COR15, CO2R15, OC(O)R15, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R15, NR16R15, coNR16R15, and C1-C6 alkylthio, C1-C6 alkylsulfinyl and C1-C6 alkylsulfonyl; R15 and R16 are independently selected at each occurrence from H, C1-C6 alkyl, C3-C10 cycloalkyl, C4-C16 cycloalkylalkyl, except that for S(O)nR15, R15 cannot be H; aryl is phenyl or naphthyl, each optionally substituted with 1 to 5 substituents independently selected at each occurrence from C1-C6 alkyl, 03- C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR15, COR15, CO2R15, OC(O)R15, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R15, NR16R15, and CONR16R15; heteroaryl is pyridyl, pyrimidinyl, triazinyl, furanyl, pyranyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, isoxazolyl, pyrazolyl, 2,3 dihydrobenzothienyl or 2, 3-dihydrobenzofuranyl, each being optionally substituted with 1 to 5 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR15, -COR15, CO2R15, OC(O)R15, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R15, NR16R15, and CONR16R15; heterocyclyl is saturated or partially saturated heteroaryl, optionally substituted with 1 to 5 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR15, COR15, CO2R15, OC(O)R15, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R15, NR15R16, and CONR16R15; n is independently at each occurrence 0, 1 or 2, with the provisos that: (1) when A is N, Z is CRê, R2 is H, R3 is -OR7 or -OCOR13, and R7 is H, then RÚ is not H, OH or SH; (2) when A is N, Z is CRê, R1 is CH3 or C2Hs, R2 is H, and R3 is OH, H, CH3, C2H5, C6Hs, n-C3H7, i-C3H7, SH, SCH3, NHC4Hg, or N(C2H5)2, then Ar is not phenyl or m-CH3-phenyl; (3) when A is N, Z is CRê, R2 is H, and Ar is pyridyl, pyrimidinyl or pyrazinyl, and R3 is NR6aR7a, then R6a and R7a are not H or alkyl; (4) when A is N, Z is CR2, and R2 is SO2NR6R7, then R3 is not OH or SH; (5) when A is CR and Z is CRê, then R2 is not-NR6SO2R7 or -SO2NR6R7; (6) when A is N, Z is CRê and R2 is -NR6S02R7 or -SO2NR6R7, then R3 is not OH or SH; (7) when A is N, Z is CRê, R1 is methyl or ethyl, R2 is H, and R3 is H, OH, CH3, C2Hs, C6H5, n-C3H7, iso-C3H7, SH, SCH3, NH(n-C4H9), or N(C2H5)2, then Ar is not unsubstituted phenyl or m-methylphenyl; (8) when A is CR, Z is CR2, R2 is H, phenyl or alkyl, R3 is NR8CoR7 and Ar is phenyl or phenyl substituted with phenylthio, then R7 is not aryl, aryl(Cl-C4 alkyl), heteroaryl, heteroaryl(C1-C4 alkyl), heterocyclyl or heterocycly(C1-C4 alkyl); (9) when A is CR, Z is CR2, R2 is H or alkyl1 Ar is phenyl, and R3 is SR13 or NR6aR7a, then R13 is not aryl or heteroaryl and R6a and R7a are not H or aryl; or (10) when A is CH, Z is CR2, R1 is OR11, R2 is H, R3 is OR7, and R7 and R11 are both H, then Ar is not phenyl, p-Br-phenyl, p-Cl-phenyl, p-NHCOCH3 phenyl, p-CH3-phenyl, pyridyl or naphthyl; (11) when A is CH, Z is CR2, R2 is H, Ar is unsubstituted phenyl, and R3 is CH3, C2H5, CF3 or C6H4F, then R1 is not CF3 or C2F5; (12) when A is CR, R is H, Z is CR2, R2 is OH, and R1 and R3 are H, then Ar is not phenyl; (13) when A is CR, R is H, Z is CR2, R2 is OH or NH2 R1 and R3 are CH3, then Ar is not 4 phenyl-3-cyano-2-aminopyrid-2-yl. [5] Preferred compounds of the above invention are compounds of Formulae (1) and (2) and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof with the additional provisos that: (1) when A is N, R1 is K, C1-C4 alkyl, halo, CN, C1-C12 hydroxyalkyl, C1-C4 alkoxyalkyl or SO2(C1-Cq alkyl), R3 is NR6aR7a and R6a is unsubstituted C1-Cq alkyl, then R7a is not phenyl, naphthyl, thienyl, benzothienyl, pyridyl, quinolyl, pyrazinyl, furanyl, benzofuranyl, benzothiazolyl, indolyl or C3-C6 cycloalkyl; and (2) A is N, R1 is H, C1-Cq alkyl, halo, CN, Cl-Cl2 hydroxyalkyl, Cl-C4 alkoxyalkyl or SO2(C1-C4 alkyl), R3 is NR6aR7a and R7a is unsubstituted Cl-C4 alkyl, then R6a is not phenyl, naphthyl, thienyl, benzothienyl, pyridyl, quinolyl, pyrazinyl, furanyl, benzofuranyl, benzothiazolyl, indolyl or C3-C6 cycloalkyl. [6] Preferred compounds of the above invention also include compounds of Formulae (1) and (2) and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein Ar is phenyl, pyridyl or 2,3-dihydrobenzofuranyl, each optionally substituted with 1 to 4 R4 substituents. [7]. Preferred compounds of the above invention also include compounds of Formulae (1) and (2) and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein A is N, Z is CR2, Ar is 2,4-dichlorophenyl, 2,4dimethylphenyl or 2,4,6-trimethylphenyl, R1 and R2 are CH3, and R3 is NR6aR7a. [11] More preferred compounds of the above invention are compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein A is N. [12] More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof. [13] More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein Ar is phenyl, pyridyl or 2,3-dihydrobenzofuranyl and each Ar is optionally substituted with 1 to 4 R4 substituents. [14j More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R3 is NR6aR7a or OR. [15] More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein Ar is phenyl, pyridyl or 2,3-dihydrobenzofuranyl, and each Ar is optionally substituted with 1 to 4 R4 substituents, and R3 is NR6aR7a or OR. [16] More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein Z is CR2 . [17] More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein Ar is phenyl, pyridyl or 2,3-dihydrobenzofuranyl and each Ar is optionally substituted with 1 to 4 R4 substituents. [18] More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R3 is NR6aR7a or OR7. [19] More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R6a is independently selected from: -H, -C1-C10 alkyl, C3-C10 alkenyl, C3-C10 alkynyl, C1-C10 haloalkyl with 1-10 halogens, C2-Cg alkoxyalkyl, C3-C6 cycloalkyl, 04- C12 cycloalkylalkyl, C5-C10 cycloalkenyl, or C6-C14 cycloalkenylalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, 03- C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(o)nRl3 COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl, -aryl, aryl(Cl-C4 alkyl)-, heteroaryl, heteroaryl(C1 C4 alkyl)-, heterocyclyl or heterocyclyl(Cl-C4 alkyl)-; and R7a is independently selected at each occurrence from: -H, -C5-C10 alkyl, C3-C10 alkenyl, C3-C10 alkynyl, C1-C10 haloalkyl with 1-10 halogens, C2-Cg alkoxyalkyl, C3-C6 cycloalkyl, 04- C12 cycloalkylalkyl, C5-C10 cycloalkenyl, or C6-C14 cycloalkenylalkyl, each optionally substituted with l to 3 substituents independently selected at each occurrence from C1-C6 alkyl, 03- C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, oC(o)R13, NR8COR15, N(coRl5)2, NR8OONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl, -aryl, aryl(C1-C4 alkyl), heteroaryl, heteroaryl(C1-C4 alkyl), heterocyclyl or heterocyclyl(C1-C4 alkyl); alternatively, NR6R7 and NR6aR7a are independently piperidine, pyrrolidine, piperazine, Nmethylpiperazine, morpholine or thiomorpholine, each optionally substituted with 1-3 C1-C4 alkyl groups. [20] More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R6a and R7a are identical and are selected from: -C1-C4 alkyl or C3-C6 cycloalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, -COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl, and -aryl or heteroaryl. [21] More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R6a is selected from: -H, -C1-C10 alkyl, C3-C10 alkenyl, C3-C10 alkynyl, Cl-Clo haloalkyl with 1-10 halogens, C2-Ca alkoxyalkyl, C3-C6 cycloalkyl, 04- C12 cycloalkylalkyl, C5-C10 cycloalkenyl, or C6-C14 cycloalkenylalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, 03- C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl, -aryl, aryl(C1-C4 alkyl), heteroaryl, heteroaryl(Cl-C4 alkyl), heterocyclyl or heterocyclyl(C1-C4 alkyl); R7a is selected from: -C1-C4 alkyl and each such C1-C4 alkyl is substituted with 1-3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CoNR16R15, NR80O2K13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl. [22] More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein one of R6a and R7a is selected from: -C3-C6 cycloalkyl, each such C3-C6 cycloalkyl optionally substituted with 1-3 substituents independently selected at each occurrence from Cl-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR8C02R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl, -aryl, -heteroaryl or -heterocyclyl, and the other of R6a and R7a is unsubstituted C1-C4 alkyl. [23] More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R6a and R7a are independently H or C1-C10 alkyl, each such C1-C10 alkyl optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, R8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl. [24] More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein Ar is pnenyl, pyridyl or 2,3-dihydrobenzofuranyl, and each Ar is optionally substituted with 1 to 4 R4 substituents, and R3 is NR6aR7a or OR7. [25] More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R6a is independently selected from: -H, -C1-C10 alkyl, C3-C10 alkenyl, C3-C10 alkynyl, C1-C10 haloalkyl with 1-10 halogens, C2-Cg alkoxyalkyl, C3-C6 cycloalkyl, 04- C12 cycloalkylalkyl, C5-C10 cycloalkenyl, or C6-C14 cycloalkenylalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, 03- C6 cycloalkyl, halo, C1-Cq haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, oC(o)R13, NR8C3R15, N(CoR15)2, NR8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl, -aryl, aryl(C1-C4 alkyl)-, heteroaryl, heteroaryl(C1-C4 alkyl), heterocyclyl or heterocyclyl(C1-C4 alkyl); R7a is independently selected at each occurrence from: -H, -C5-C10 alkyl, C3-C10 alkenyl, C3-C10 alkynyl, C1-C10 haloalkyl with 1-10 halogens, C2-Cg alkoxyalkyl, C3-C6 cycloalkyl, 04- C12 cycloalkylalkyl, C5-C10 cycloalkenyl, or C6-C14 cycloalkenylalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, 03- C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NK8OOK15, N(COR15)2t NR8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl, -aryl, aryl(C1-Cq alkyl), heteroaryl, heteroaryl(C1-C4 alkyl), heterocyclyl or heterocyclyl(C1-C4 alkyl), alternatively, NR6R7 and NR6aR7a are independently piperidine, pyrrolidine, piperazine, Nmethylpiperazine, morpholine or thiomorpholine, each optionally substituted with 1-3 C1-C4 alkyl groups. [26] More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R6a and R7a are identical and are selected from: -C1-C4 alkyl or C3-C6 cycloalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(o)nRl3 -COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl, and -aryl or heteroaryl. [27] More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R6a and R7a are identical and are -Cl-C4 alkyl, each such C1-C4 alkyl optionally substituted with 1 to 3 substituents independently selected at each occurrence from Cl-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, -COR15, CO2R15, OC (o) R13, NK8OOK1S, N(COR15)2, NR8CONR16R15, NR8CO2R13,.NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl. [28] More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R6a is selected from: -H, -C1-C10 alkyl, C3-C10 alkenyl, C3-C10 alkynyl, C1-C10 haloalkyl with 1-10 halogens, C2-Cg alkoxyalkyl, C3-C6 cycloalkyl, 04- C12 cycloalkylalkyl, C5-C10 cycloalkenyl, or C6-C14 cycloalkenylalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, 03- C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl, -aryl, aryl(C1-Cq alkyl), heteroaryl, heteroaryl(C1-C4 alkyl), heterocyclyl or heterocyclyl(C1-C4 alkyl); R7a is: -C1-C4 alkyl and each such C1-C4 alkyl is substituted with 1-3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR8Co2Rl3t NR16R15t CoNR16R15, aryl, heteroaryl or heterocyclyl. [29] More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein one of R6a and R7a is selected from: -C3-C6 cycloalkyl, each such C3-C6 cycloalkyl optionally substituted with 1-3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl, -aryl, -heteroaryl or -heterocyclyl, and the other of R6a and R7a is unsubstituted C1-C4 alkyl. [30] More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof1 or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R6a and R7a are independently H or C1-C10 alkyl, each such C1-C10 alkyl optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl1 C3-C6 cycloalkyl, halo, Cl-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, R8CoNR16Rl5, NR80O2K13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl. [31] More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein -Ar is phenyl, pyridyl or 2,3-dihydrobenzofuranyl, and each Ar is optionally substituted with 1 to 4 R4 substituents, -R3 is NR6aR7a or OR7 and -R1 and R2 are independently selected from H, C1-C4 alkyl, C3-C6 cycloalkyl, C4-C1o cycloalkylalkyl. [32] More preferred compounds of the above invention also include compounds and isomers thereof 1 stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R6a is independently selected from: -H, -C1-C10 alkyl, C3-C10 alkenyl, C3-C10 alkynyl, C1-C10 haloalkyl with 1-10 halogens, C2-Cg alkoxyalkyl, C3-C6 cycloalkyl, 04- C12 cycloalkylalkyl, C5-C10 cycloalkenyl, or C6-C14 cycloalkenylalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, 03- C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl, -aryl, aryl(C1-C4 alkyl)-, heteroaryl, heteroaryl(C1 C4 alkyl)1 heterocyclyl or heterocyclyl(C1-C4 alkyl); R7a is independently selected at each occurrence from: -H, -C5-C10 alkyl, C3-C10 alkenyl, C3-C10 alkynyl, C1-C10 haloalkyl with 1-10 halogens, C2-C8 alkoxyalkyl, C3-C6 cycloalkyl, 04- C12 cycloalkylalkyl, C5-C10 cycloalkenyl, or C6-C14 cycloalkenylalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, 03- C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl, -aryl, aryl(C1-C4 alkyl), heteroaryl, heteroaryl(C1-C4 alkyl), heterocyclyl or heterocyclyl(C1-C4 alkyl), alternatively, NR6R7 and NR6aR7a are independently piperidine, pyrrolidine, piperazine, Nmethylpiperazine, morpholine or thiomorpholine, each optionally substituted with 1-3 C1-C4 alkyl groups. [33] More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R6a and R7a are identical and are selected from: -C1-C4 alkyl or C3-C6 cycloalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR131 -00K15, C02R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NK8002K13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl, and -aryl or heteroaryl. [34] More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R6a and R7a are identical and are -C1-C4 alkyl, each such C1-C4 alkyl optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo1 C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR131 -COR15, C02R15, OC (O) R13, NR8COR15, N(COR15)2, NR8CONR16Rl5, NR8CC2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl. [35] More preferred compounds of the above invention also include compounds and isomers thereof 1 stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R6a is selected from: -H, -C1-C10 alkyl, C3-C10 alkenyl, C3-C10 alkynyl, C1-C10 haloalkyl with 1-10 halogens, C2-Cg alkoxyalkyl, C3-C6 cycloalkyl, 04- C12 cycloalkylalkyl, C5-C10 cycloalkenyl, or C6-C14 cycloalkenylalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, 03- C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR80O2R131 NR16R15, CONR16Rl5, aryl, heteroaryl or heterocyclyl, -aryl, aryl(C1-C4 alkyl), heteroaryl, heteroaryl(Cl-Cq alkyl), heterocyclyl or heterocyclyl(C1-C4 alkyl); R7a is: -C1-C4 alkyl and each such C1-C4 alkyl is substituted with 1-3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, Cl-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl. [36] More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof 1 or mixtures of stereoisomeric forms thereof1 and pharmaceutically acceptable salt or pro-drug forms thereof wherein one.of R6a and R7a is selected from: -C3-C6 cycloalkyl, each such C3-C6 cycloalkyl optionally substituted with 1-3 substituents independently selected at each occurrence from C1-C6 alkyl1 C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl, -aryl, -heteroaryl or -heterocyc lyl, and the other of R6a and R7a is unsubstituted C1-C4 alkyl. [37] More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R6a and R7a are independently H or C1-C10 alkyl, each such Cl-Clo alkyl optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, R8CoNR16Rl5, NK80O2K13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl. [38] Specifically preferred compounds of the above invention are compounds of Formula (50) EMI42.1 FORMULA (50) and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof 1 and pharmaceutically acceptable salt or pro-drug forms thereof, selected from the group consisting of: a compound of Formula (50) wherein R3 is -NHCH(n-Pr)2, R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(Et)(n-Bu), R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -(n Pr) (CH2cPr), R4a is Cl, R4b is H, R4c is Cl, K 4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(CH2CH2OMe)2, R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Et)(n Bu), R4a is Cl, R4b is H, R4c is C1, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Et) (CH2OMe), R4a is C1, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(CH2OMe)2, R4a is C1, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(Et)2, R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(CH2OEt)2, R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Et)2, R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(Me) (Ph), R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(n-Pr)2, R4a is Cl, R4b is H, R4c is C1, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Et)(n Pr), R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(CH2OMe)2, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is Me; a compound of Formula (50) wherein R3 is -NHCH(CH2OMe)2, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(CH2CH2OMe)2, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Et)(CH2OMe), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Et)2, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -OEt, R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(Et)2, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(CH2CN)2, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Me) (CH2OMe), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -OCH(Et) (CH2OMe), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(n Pr) (CH2cPr), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Me) (CH2N(Me)2), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(cPr) (CH2CH2CN), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(n Pr) (CH2CH2CN), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(n Bu) (CH2CN), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Et) (CH2OMe), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is Me; a compound of Formula (50) wherein R3 is -NHCH(Et)2, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is Me; a compound of Formula (50) wherein R3 is -N(CH2CH2OMe)2, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is Me; a compound of Formula (50) wherein R3 is -NHCH(CH2OMe)2, R4a is Br, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Et) (CH2OMe), R4a is Br, R4b is H, R4c is OMe, R4d is H and R4e is a compound of Formula (50) wherein R3 is -N(Et)2, R4a is Me, R4b is H, R is Me, R4d is H and R4e is Me; a compound of Formula (50) wherein R3 is -NHCH(CH2OEt)2, R4a is Me, R4b is H, R@@ is Me, R4d is H and R4e is Me; a compound of Formula (50) wherein R3 is -NHCH(CH2CH2OMe) (CH2OMe)2, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is Me; a compound of Formula (50) wherein R3 is morpholino, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(CH2CH2OMe)2, R4a is Br, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Et)2, R4a is Br, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(Et)2, R4a is Br, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NH(c-Pr), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(CH2OMe)2, R4a is CN, R4b is K, R4c is OMe, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(c Pr) (CH2CH2CN), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is Me; a compound of Formula (50) wherein R3 is -NCH(CH2OMe)2, R4a is Me, R4b is H, R4c is Br, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(CH2OMe) (CH2CH2OMe), R4a is Me, R4b is H, R4c is Br, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(CH2OMe)2, R4a is Me, R4b is H, K 4c is OMe, R4d is Me and R4e is H; a compound of Formula (50) wherein R3 is -N(CH2CH2OMe)2, R4a is Me, R4b is H, R4c is OMe, R4d is Me and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Et)2, R4a is Me, R4b is H, R4c is OMe, R4d is Me and R4e is H; a compound of Formula (50) wherein a compound of Formula (50) wherein R3 is -N(Et)2, R4a is Me, R4b is H, R4c is OMe, R4d is Me and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(CH2OMe)2, R4a is Cl, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Et)(CH2OMe), R4a is Cl, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(CH2CH2OMe)2, R4a is Cl, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(CH2OMe) (CH2CH2OMe), R4a is C1, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(c Pr) (CH2CH2CN), R4a is Me, R4b is H, R4c is OMe, R4d is Me and R4e is H; a compound of Formula (50) wherein R3 is -N(c Pr) (CH2CH2CN), R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is (S) NHCH(CH2OMe) (CH2CH2OMe), R4a is Cl, R4b is H, R4c is C1, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(CH2OMe) (CH2CH2OMe), R4a is C1, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Et)2, R4a is Me, R4b is H, R4c is Br, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(CH2CH2OMe)2, R4a is Me, R4b is H, R4c is Br, R4d is H and R4e is H; a compound of Formula (50) wherein R is -NH(CH2OMe) (CH2-iPr), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(CH2CH2OMe)2, 4a is Me, R4b is H, R4c is H, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(CH2CH2OMe)2, R4a is Me, R4b is H, R4c is NMe2, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(CH2OMe) (n-Pr), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(CH2OEt) (Et), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(CH2OMe) (CH2CH2OMe), R4a is Me, R4b is H, R4c is NMe2, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(Et)2, R4a is Me, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R is -NHCH(Et)2, R4a is Me, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(CH2CH2OMe)2, R4a is Me, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(CH2OMe)2, R4a is Me, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(Et)2, R4a is Me, R4b is H, R4c is Br, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(Et)2, R4a is Cl, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Et)2, R4a is Cl, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Et)2, R4a is Me, R4b is H, R4c is NMe2, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is (S) NHCH(CH2OMe) (CH2CH2OMe), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(CH2OMe) (CH2CH2OMe), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is (S) NHCH(CH2OMe) (CH2CH2OMe), R4a is Me, R4b is H, R4c is C1, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(CH2OMe)(CH2CH2OMe), R4a is Me, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(c Pr)(CH2CH2CN), R4a is Me, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NH(Et)(CH2CN), R4a is Me, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(Et)2, R4a is Me, R4b is Me, R4c is OMe, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(CH2CH2OMe) (CH2CH2OH), R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(CH2CH2OMe)2, R4a is Me, R4b is Me, R@@ is OMe, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Et)2, R4a is Me, R@@ is Me, R4c is OMe, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(CH2c-Pr) (n Pr), R4a is Me, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(c-Pr) (CH2CH2CN), R4a is Me, R4b is Me, R4c is OMe, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH (Et)2, R4a is Cl, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(Et)2, R4a is Cl, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(CH2CH2OMe)2, R4a is Cl, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Et) (CH2OMe), R4a is Cl, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(Et)2, R4a is Cl, R4b is H, R4c is CN, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(c Pr) (CH2CH2CN), R4a is Cl, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(CH2OH)2, R is C1, R4b is H, K4c is Cl, R4d is H and R4e is H; and a compound of Formula (50) wherein R3 is N(CH2CH2OMe)2, R4a is Me, R4b is H, R4c is OMe, R4d is H and R4e is H. [39] More specifically preferred is 4-(bis-(2 methoxyethyl) amino) -2, 7-dimethyl-8- (2-methyl-4- methoxyphenyl)-[1,5-a]-pyrazolo-1,3,5-triazine and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof. [40] More specifically preferred is 4-(bis-(2methoxyethyl)amino)-2,7-dimethyl-8-(2,5-dimethyl-4methoxyphenyl)-[1,5-a]-pyrazolo-1,3,5-triazine and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof. [41] More preferred are compounds of the above invention are compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein A is CR. [42] More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof. [43] More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein Ar is phenyl, pyridyl or 2,3-dihydrobenzofuranyl and each Ar is optionally substituted with 1 to 4 R4 substituents. [44] j More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R3 is NR6aR7a or OR7. [45] More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein Ar is phenyl, pyridyl or 2,3-dihydrobenzofuranyl, and each Ar is optionally substituted with 1 to 4 R4 substituents, and R3 is NR6aR7a or OR7. [46] More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein Z is CR2 . [47] More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein Ar is phenyl, pyridyl or 2,3-dihydrobenzofuranyl and each Ar is optionally substituted with 1 to 4 R4 substituents. [48] More preferred compounds of the above invention also include compounds and isomers thereof 1 stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R3 is NR6aR7a or OR7. [49] More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein Ar is phenyl, pyridyl or 2,3-dihydrobenzofuranyl, and each Ar is optionally substituted with 1 to 4 R4 substituents, and R3 is NR6aR7a or OR7. [50] More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R6a and R7a are independently H or C1-C10 alkyl, and each such C1-C10 alkyl is optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, 03- C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, R8CONR16R15 NK80O2K13, NR16R15, CoNR16Rl5, aryl, heteroaryl or heterocyclyl. [51] More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein -Ar is phenyl, pyridyl or 2,3-dihydrobenzofuranyl, and each Ar is optionally substituted with I to 4 R4 substituents, -R3 is NR6aR7a or OR7 and -RÚ and R2 are independently selected from H, C1-C4 alkyl1 C3-C6 cycloalkyl, C4-C1t cycloalkylalkyl. [52] More preferred compounds of the above invention also include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R6a and R7a are independently H or C1-C10 alkyl1 and each such C1-C10 alkyl is optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, 03- C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, R8CONR16R15, NR8CO2R13, NR16R15, CoNRl6Rl5, aryl, heteroaryl or heterocyclyl. [53] Specifically preferred compounds of the above invention are compounds of Formula (51) EMI54.1 FORMULA (51) and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof selected from the group consisting of: a compound of Formula (51) wherein R3 is -NHCH(n-Pr)2, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NHCH(CH2OMe)2, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -N(CH2CH2OMe)2, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -N(c Pr) (CH2CH2CN), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -N(CH2CH2OMe)2, R4a is Cl, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NHCH(CH2OMe)2, R4a is Cl, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is is Cl, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R is -N(Et)2, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -N(n- Pr) (CH2CH2CN), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -N(n Bu) (CH2CH2CN), R4a is Me, R4b is H, K4 c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NHCH(n Pr) (CH2OMe), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NHCH(Et)2, R4a is Me, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NHCH(CH2OMe)2, R4a is Me, R4b is H; R4c is OMe, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is (S) -NH(CH2CH2OMe)CH2OMe, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NH(CH2CH2OMe)CH2OMe, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -N(CH2CH2OMe)2, R4a is Me, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NH(Et), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NHCH(n-Pr)2, R4a is Me, R4b is H, R4c is C1, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NHCH(CH2OMe)2, R4a is Me, R4b is H, R4c is C1, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is (S) -NH(CH2CH2OMe)CH2OMe, R4a is Me, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NH(CH2CH2OMe)CH2OMe, R4a is Me, R4b is H, R4c is C1, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -N(n Pr) (CH2CH2CN), R4a is Me, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -N(Et)2, R4a is Me, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is (S) -NH(CH2CH2OMe)CH2OMe, R4a is Cl, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NH(CH2CH2OMe)CH2OMe, R4a is Cl, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -N(Et)2, R4a is Cl, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -N(c Pr) (CH2CH2CN), R4a is Me, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -N(c Pr) (CH2CH2CN), R4a is Cl, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NHCH (n Pr) (CH2OMe), R4a is Me, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NHCH (n Pr) (CH2OMe), R4a is Cl, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NHCH(Et)2, R4a is Br, R4b is H, R4c is OMe, R4d is OMe and R4e is H; a compound of Formula (51) wherein R3 is -NHCH(Et)2, R4a is Br, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -N(CH2CH2OMe)2, R4a is Br, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NHCH(CH2OMe)2, R4a is Br, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -N(Et)2, R4a is Me, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -N(Et)2, R4a is Cl, R4b is H, R4c is OMe, R4d is OMe and R4e is H; a compound of Formula (51) wherein R3 is -NHCH(Et)2, R4a is Cl, R4b is H, R4c is OMe, R4d is OMe and R4e is H; a compound of Formula (51) wherein R3 is -N(CH2CH2OMe)2, R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (51) wherein K3 is -NHCH(CH2OMe)2, R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -N(Pr) (CH2CH2CN), R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -N(Bu)(Et), R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NHCH(Et)CH2OMe, R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NHCH(Et)2, R4a is C1, R4b is H, K 4c is Cl, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NHCH(Et)2, ,4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NHCH(Et)2, R4a is Cl, R4b is H, R4c is Me, K4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NHCH(Et)2, R4a is Me, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NEt2, R4a is Me, R4b is H, R4c is OMe, R4d is H and R4e is H; and a compound of Formula (51) wherein R3 is -N(Pr) (CH2CH2CN), R4a is Me, R4b is H, R4c is OMe, R4d is H and R4e is H. [54] More specifically preferred is 7-(3pentylamino)-2,5-dimethyl-3-(2-methyl-4methoxyphenyl)-[1,5-a]-pyrazolopyrimidine and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof. [55] More specifically preferred is 7-(Diethylamino)2,5-dimethyl-3-(2-methyl-4-methoxyphenyl-[1,5-a]pyrazolopyrimidine and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof. [56j More specifically preferred is 7-(N-(3cyanopropyl)-N-propylamino)-2,5-dimethyl-3-(2,4dimethylphenyl)-[1,5-a]-pyrazolopyrimidine and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof. The present invention also provides pharmaceutical compositions comprising compounds of Formulae (1) and (2) and a pharmaceutically acceptable carrier. 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, 0=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 materia like. "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, such as ethynyl, propynyl and the like. "Haloalkyl" is intended to include both branched and straight-chain alkyl having the specified number of carbon atoms1 substituted with 1 or more halogen; "alkoxy" represents an alkyl group of indicated number of carbon atoms attached through an oxygen bridge; "cycloalkyl" is intended to include saturated ring groups, including mono-,bi- or poly-cyclic ring systems, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and so forth. "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 substitent 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 "appropriate amino acid protecting group" means any group known in the art of organic synthesis for the protection of amine or carboxylic acid groups. Such amine protecting groups include those listed in Greene and Wuts, "Protective Groups in Organic Synthesis" John Wiley & Sons, New York (1991) and "The Peptides: Analysis, Synthesis, Biology, Vol. 3, Academic Press, New York (1981), the disclosure of which is hereby incorporated by reference. Any amine protecting group known in the art can be used. Examples of amine protecting groups include, but are not limited to, the following: 1) acyl types such as formyl, trifluoroacetyl, phthalyl, and p-toluenesulfonyl; 2) aromatic carbamate types such as benzyloxycarbonyl (Cbz) and substituted bezyloxycarbonyls, l-(p-biphenyl)-1methylethoxycarbonyl, and 9-fluorenylmethyloxycarbonyl (Fmoc) ; 3) aliphatic carbamate types such as tert-butyloxycarbonyl (Boc), ethoxycarbonyl, diisopropylmethoxycarbonyl, and allyloxycarbonyl; 4) cyclic alkyl carbamate types such as cyclopentyloxycarbonyl and adamantyloxycarbonyl; 5) alkyl types such as triphenylmethyl and benzyl; 6) trialkylsilane such as trimethylsilane; and 7) thiol containing types such as phenylthiocarbonyl and dithiasuccinoyl. The term "pharmaceutically acceptable salts" includes acid or base salts of the compounds of Formulae (1) and (2). 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 Remlngton'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) or (II) in vivo when such prodrug is administered to a mammalian subject. Prodrugs of the compounds of formula (I) and (II) 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 formulas (I) and (II); and the like. The term "therapeutically effective amount" of a compound of this invention means an amount effective to antagonize abnormal level of ORF or treat the symptoms of affective disorder, anxiety or depression in a host. Svntheses Some compounds of Formula (1) may be prepared from intermediate compounds of Formula (7), using the procedures outlined in Scheme 1: SCHEME 1 EMI63.1 <tb> <SEP> Y <SEP> halogenating <SEP> agent <SEP> or <SEP> X <tb> <SEP> sulfonylating <SEP> agent <tb> <SEP> HN <SEP> + <SEP> + <SEP> / <SEP> - <SEP> base, <SEP> + <SEP> / <SEP> - <SEP> solvent <SEP> v <SEP> \ <SEP> N <SEP> ¯ <tb> <SEP> z <tb> R1 <SEP> R1/N/ <tb> <SEP> Ar <SEP> Ar <tb> <SEP> (7) <SEP> Y <SEP> = <SEP> O <SEP> (8) <tb> <SEP> R3 <tb> <SEP> R3H, <SEP> + <SEP> / <SEP> - <SEP> base, <SEP> A <tb> <SEP> + <SEP> + <SEP> / <SEP> - <SEP> solvent <SEP> A <SEP> C <tb> <SEP> + <SEP> / <SEP> - <SEP> solvent <SEP> Z <tb> <SEP> Ar <tb> (1) A = N Compounds of Formula (7) (where Y is 0) may be treated with a halogenating agent or sulfonylating agent in the presence or absence of a base in the presence or absence of an inert solvent at reaction temperatures ranging from -800C to 250 C to give products of Formula (8) (where X is halogen, alkanesulfonyloxy, arylsulfonyloxy or haloalkane-sulfonyloxy) . Halogenating agents include, but are not limited to, SOCl2, POOl3, PCl3, Pals, POBr3, PBr3 or PBr5. Sulfonylating agents include, but are not limited to, alkanesulfonyl halides or anhydrides (such as methanesulfonyl chloride or methanesulfonic acid anhydride), arylsulfonyl halides or anhydrides (such as p-toluenesulfonyl chloride or anhydride) or haloalkylsulfonyl halides or anhydrides (preferably trifluoromethanesulfonic anhydride). Bases may include, but are not limited to, alkali metal hydrides (preferably sodium hydride) , alkali metal alkoxides (1 to 6 carbons) (preferably sodium methoxide or sodium ethoxide), alkaline earth metal hydrides, alkali metal dialkylamides (preferably lithium diisopropylamide), alkali metal bis(trialkylsilyl)amides (prefsrably sodium bis(trimethylsilyl)amide), trialkyl amines (preferably N,N-di-isopropyl-N-ethyl amine or triethylamine) or aromatic amines (preferably pyridine). Inert solvents may include, but are not limited to, lower alkanenitriles (1 to 6 carbons, preferably acetonitrile), dialkyl ethers (preferably diethyl ether), cyclic ethers (preferably tetrahydrofuran or 1,4-dioxane), N,N-dialkylformamides (preferably dimethylformamide), N, N-dialkylacetamides (preferably dimethylacetamide) , cyclic amides (preferably Nmethylpyrrolidin-2-one), dialkylsulfoxides (preferably dimethylsulfoxide), aromatic hydrocarbons (preferably benzene or toluene) or haloalkanes of 1 to 10 carbons and 1 to 10 halogens (preferably dichloromethane). Preferred reaction temperatures range from -200C to 10000. Compounds of Formula (8) may be reacted with compounds of Formula R3H (where R3 is defined as above except R3 is not SH, CCR7, Co2R7, aryl or heteroaryl) in the presence or absence of a base in the presence or absence of an inert solvent at reaction temperatures ranging from -80 to 2500C to generate compounds of Formula (1). Bases may include, but are not limited to, alkali metal hydrides (preferably sodium hydride), alkali metal alkoxides (1 to 6 carbons) (preferably sodium methoxide or sodium ethoxide) , alkaline earth metal hydrides, alkali metal dialkylamides (preferably lithium di-isopropylamide), alkali metal carbonates, alkali metal bicarbonates, alkali metal bis (trialkylsilyl) amides (preferably sodium bis(trimethylsilyl)amide), trialkyl amines {preferably N,N-di-isopropyl-N-ethyl amine) or aromatic amines (preferably pyridine). Inert solvents may include, but are not limited to, alkyl alcohols (1 to 8 carbons, preferably methanol or ethanol), lower alkanenitriles (1 to 6 carbons, preferably acetonitrile), dialkyl ethers (preferably diethyl ether) I cyclic ethers (preferably tetrahydrofuran or 1,4-dioxane), N,N-dialkylformamides (preferably dimethylformamide), N,N-dialkylacetamides (p,eferably dimethylacetamide) , cyclic amides (preferably N-methylpyrrolidin-2-one), dialkylsulfoxides (preferably dimethylsulfoxide), aromatic hydrocarbons (preferably benzene or toluene) or haloalkanes of 1 to 10 carbons and 1 to 10 halogens (preferably dichloromethane) . Preferred reaction temperatures range from OOC to 1400C. Scheme 2 delineates the procedures for converting intermediate compounds of Formula (7) (where Y is S) to some compounds of Formula (1). SCHEME 2 EMI66.1 <tb> <SEP> Y <SEP> SR13 <tb> <SEP> R13X, <SEP> + <SEP> I <SEP> - <SEP> base, <SEP> NY <tb> R1 <SEP> 1 <SEP> N <SEP> 9 <SEP> Z <tb> <SEP> Ar <SEP> Ar <tb> <SEP> (7) <SEP> Y <SEP> = <SEP> S <SEP> / <SEP> (12) <tb> <SEP> oxidizing <SEP> agent, <tb> <SEP> solvent <SEP> / <SEP> H, <SEP> + <SEP> / <SEP> - <SEP> base, <tb> <SEP> + <SEP> / <SEP> - <SEP> solvent <tb> <SEP> S <SEP> (0) <SEP> R13 <SEP> R3 <tb> <SEP> NYN <SEP> NX <SEP> R3s, <SEP> + <SEP> / <SEP> - <SEP> base, <tb> <SEP> - <SEP> --iC <SEP> + <SEP> / <SEP> - <SEP> aolventN/ <tb> <SEP> RlJ < NJef <SEP> R1X9+N <SEP> /S <tb> <SEP> R1 <tb> <SEP> Ar <tb> <SEP> Ar <tb> (13) (1) A = N Compounds of Formula (7) (where Y is S) may be treated with an alkylating agent R13X (where R13 is defined as above, except R13 is not aryl or heteroaryl) in the presence or absence of a base in the presence or absence of an inert solvent at reaction temperatures ranging from -800C to 250 C. Bases may include, but are not limited to, alkali metal hydrides (preferably sodium hydride)1 alkali metal alkoxides (1 to 6 carbons) (preferably sodium methoxide or sodium ethoxide), alkaline earth metal hydrides, alkali metal dialkylamides (preferably lithium di-isopropylamide), alkali metal carbonates, alkali metal hydroxides, alkali metal bis(trialkylsilyl)amides (preferably sodium bis(trimethylsilyl)amide), trialkyl amines (prefereably N,N-di-isopropyl-N-ethyl amine or triethyl amine) or aromatic amines (preferably pyridine). Inert solvents may include, but are not limited to, alkyl alcohols (1 to 8 carbons, preferably methanol or ethanol)1 lower alkanenitriles (1 to 6 carbons, preferably acetonitrile), dialkyl ethers (preferably diethyl ether), cyclic ethers (preferably tetrahydrofuran or 1,4-dioxane), N,N-dialkylformamides (preferably dimethylformamide), N,N-dialkylacetamides (preferably dimethylacetamide) , cyclic amides (preferably Nmethylpyrrolidin-2-one), dialkylsulfoxides (preferably dimethylsulfoxide), aromatic hydrocarbons (preferably benzene or toluene) or haloalkanes of 1 to 10 carbons and 1 to 10 halogens (preferably dichloromethane). Preferred reaction temperatures range from -800C to 1000C. Compounds of Formula (12) (Formula (1) where R3 is SR13) may then be reacted with compounds of Formula R3H to give compounds of Formula (1), using the same conditions and reagents as were used for the conversion of compounds of Formula (8) to compounds of Formula (1) as outlined for Scheme 1 above. Alternatively, compounds of Formula (12) (Formula (1) where R3 is SR13) may be oxidized to compounds of Formula (13) (Formula (1) where R3 is S(o)nRl3 n is 1,2) by treatment with an oxidizing agent in the presence of an inert solvent at temperatures ranging from -80 C to 2500C. Oxidizing agents include, but are not limited to, hydrogen peroxide, alkane or aryl peracids (preferably peracetic acid or m-chloro-perbenzoic acid), dioxirane, oxone, or sodium periodate. Inert solvents may include, but are not limited to, alkanones (3 to 10 carbons1 preferably acetone), water, alkyl alcohols (1 to 6 carbons) 1 aromatic hydrocarbons (preferably benzene or toluene) or haloalkanes of 1 to 10 carbons and 1 to 10 halogens (preferably dichloromethane) or combinations thereof. The choices of oxidant and solvent are known to those skilled in the art (cf. Uemura, S., Oxidation of Sulfur, Selenium and Tellurium, in Comprehensive Organic Synthesis, Trost, B.M. ed., (Elmsford, NY: Pergamon Press, 1991), 7, 762-769). Preferred reaction temperatures range from -20 C to 100 C. Compounds of Formula (13) (Formula (1) where R3 is S(O)nR13, n is 1,2) may then be reacted with compounds of Formula R3H to give compounds of Formula (1), using the same conditions and reagents as were used for the conversion of compounds of Formula (8) to compounds of Formula (1) as outlined for Scheme (1) above. Compounds of Formula (1), where R3 may be -NR8COR7, -N(COR7)2, -NR8CONR6R7, -NR8CO2R13, -NR6R7, -NR8SO2R7, may be prepared from compounds of Formula (7), where Y is NH, by the procedures depicted in Scheme 3. SCHEME 3 EMI68.1 <tb> <SEP> y <SEP> R3 <tb> <SEP> alkylating, <SEP> sulfonylating <tb> <SEP> ERIN <SEP> or <SEP> r <SEP> acylating <SEP> agents <tb> <SEP> - <SEP> + <SEP> / <SEP> base,solvent <SEP> solvent¯ANN\\z <tb> R1 <SEP> <SEP> N <SEP> z <SEP> Rl <tb> <SEP> Ar <SEP> Ar <tb> <SEP> (7) <SEP> Y <SEP> = <SEP> NH <SEP> (1) <tb> A = N; R3 = NR6R7,NR8COR7, N(COR7)2, NR8CONR6R7, NR8Co2Rl3 Reaction of compounds of Formula (7), where Y is NH, with alkylating agents1 sulfonylating agents or acylating agents or sequential reactions with combinations thereof1 in the presence or absence of a base in an inert solvent at reaction temperatures ranging from -80 C to 250 C may afford compounds of Formula (1), where R3 may be -NR8COR7, -N(CoR7)2, -NR8CONR6R7, -NR8CO2R13, -NR6R7, -NR8SO2R7. Alkylating agents may include, but are not limited to, C1-C10 alkyl -halides1 -tosylates, -mesylates or -triflates; C1-C10 haloalkyl(1 - 10 halogens)-halides, -tosylates, -mesylates or -triflates; C2-Cg alkoxyalkyl-halides, -tosylates, -mesylates or -triflates; C3-C6 cycloalkylhalides, -tosylates, -mesylates or -triflates; 04- C12 cycloalkylalkyl-halides, -tosylates, -mesylates or -triflates; aryl(C1-C4 alkyl)-halides, -tosylates, -mesylates or -triflates; heteroaryl(C1-C4 alkyl)halides, -tosylates, -mesylates or -triflates; or heterocyclyl(C1-C4 alkyl)-halides, -tosylates, -mesylates or -triflates. Acylating agents may include, but are not limited to, C1-C10 alkanoyl halides or anhydrides, C1-C10 haloalkanoyl halides or anhydrides with 1 - 10 halogens1 C2-Cg alkoxyalkanoyl halides or anhydrides, C3-C6 cycloalkanoyl halides or anhydrides, C4-C12 cycloalkylalkanoyl halides or anhydrides, aroyl halides or anhydrides, aryl(C1-C4) alkanoyl halides or anhydrides, heteroaroyl halides or anhydrides, heteroaryl(C1-C4) alkanoyl halides or anhydrides, heterocyclylcarboxylic acid halides or anhydrides or heterocyclyl(C1-C4) alkanoyl halides or anhydrides. Sulfonylating agents include, but are not limited to, C1-C10 alkylsulfonyl halides or anhydrides, C1-C10 haloalkylsulfonyl halides or anhydrides with 1 - 10 halogens, C2-Cg alkoxyalkylsulfonyl halides or anhydrides, C3-C6 cycloalkylsulfonyl halides or anhydrides, C4-Cl2 cycloalkylalkylsulfonyl halides or anhydrides, arylsulfonyl halides or anhydrides, aryl(Cl- C4 alkyl)-, heteroarylsulfonyl halides or anhydrides, heteroaryl(C1-Cg alkyl)sulfonyl halides or anhydrides, heterocyclylsulfonyl halides or anhydrides or heterocyclyl(C1-Cq alkyl)sulfonyl halides or anhydrides. Bases may include, but are not limited to, alkali metal hydrides (preferably sodium hydride), alkali metal alkoxides (1 to 6 carbons) (preferably sodium methoxide or sodium ethoxide), alkaline earth metal hydrides, alkali metal dialkylamides (preferably lithium diisopropylamide), alkali metal carbonates, alkali metal bis (trialkylsilyl) amides (preferably sodium bis(trimethylsilyl)amide), trialkyl amines (prefereably di-isopropylethyl amine) or aromatic amines (preferably pyridine). Inert solvents may include, but are not limited to, alkyl alcohols (1 to 8 carbons1 preferably methanol or ethanol), lower alkanenitriles (1 to 6 carbons1 preferably acetonitrile), dialkyl ethers (preferably diethyl ether), cyclic ethers (preferably tetrahydrofuran or 1,4-dioxane), N,N-dialkylformamides (preferably dimethylformamide) 1 N,N-dialkylacetamides (preferably dimethylacetamide), cyclic amides (preferably N-methylpyrrolidin-2-one), dialkylsulfoxides (preferably dimethylsulfoxide) or aromatic hydrocarbons (preferably benzene or toluene) . Preferred reaction temperatures range from OOC to 1000C. Scheme 4 delineates procedures, which may be employed to prepare intermediate compounds of Formula (7), where Y is O, S and Z is CR2. SCHEME 4 EMI71.1 <tb> <SEP> 0 <tb> <SEP> R2CORb, <SEP> base, <SEP> NC <SEP> t <SEP> NH2NH2 <SEP> - <SEP> H2O, <tb> ArCR2CN <SEP> solvent <SEP> R2 <SEP> solvent <tb> <SEP> Awl: <SEP> (3) <tb> <SEP> NB <tb> <SEP> R1/ <tb> <SEP> N <SEP> R <SEP> (5) <SEP> ore <SEP> A <tb> <SEP> HN <SEP> + <SEP> / <SEP> - <SEP> acid, <SEP> NH <SEP> N <tb> <SEP> R2 <SEP> solvent <SEP> R2 <tb> <SEP> H <tb> <SEP> R2N <SEP> (6) <SEP> ' <SEP> R1 <SEP> N <tb> <SEP> (4) <SEP> Ar <SEP> (6) <SEP> Ar <tb> <SEP> y=c(Rd)2, <SEP> base, <SEP> RN <tb> <SEP> 2 <tb> <SEP> solvent <tb> <SEP> R1 <SEP> N <tb> <SEP> Ar <tb> (7) Y = O, S; Z = CR2 Compounds of the formula ArCH2CN are reacted with compounds of the formula R2CORb, where R2 is defined above and Rb is halogen, cyano, lower alkoxy (1 to 6 carbons) or lower alkanoyloxy (1 to 6 carbons), in the presence of a base in an inert solvent at reaction temperatures ranging from -78 C to 200 C to afford compounds of Formula (3). Bases may include, but are not limited to, alkali metal hydrides (preferably sodium hydride), alkali metal alkoxides (1 to 6 carbons) (preferably sodium methoxide or sodium ethoxide), alkaline earth metal hydrides, alkali metal dialkylamides (preferably lithium di-isopropylamide) alkali metal carbonates, alkali metal hydroxides, alkali metal bis(trialkylsilyl)amides (preferably sodium bis(trimethylsilyl)amide), trialkyl amines (preferably N,N-di-isopropyl-N-ethyl amine) or aromatic amines (preferably pyridine). Inert solvents may include, but are not limited to, alkyl alcohols (1 to 8 carbons, preferably methanol or ethanol), lower alkanenitriles (1 to 6 carbons, preferably acetonitrile) , water1 dialkyl ethers (preferably diethyl ether), cyclic ethers (preferably tetrahydrofuran or 1,4-dioxane), N;Ndialkylformamides (preferably dimethylformamide), N,Ndialkylacetamides (preferably dimethylacetamide), cyclic amides (preferably N-methylpyrrolidin-2-one), dialkylsulfoxides (preferably dimethylsulfoxide) or aromatic hydrocarbons (preferably benzene or toluene). Preferred reaction temperatures range from OOC to 1000C. Compounds of Formula (3) may be treated with hydrazine-hydrate in the presence of an inert solvent at temperatures ranging from OOC to 2000C, preferably 700C to 1500C, to produce compounds of Formula (4). Inert solvents may include, but are not limited to, water, alkyl alcohols (1 to 8 carbons, preferably methanol or ethanol), lower alkanenitriles (1 to 6 carbons, preferably acetonitrile), cyclic ethers (preferably tetrahydrofuran or 1,4-dioxane), N,N-dialkylformamides (preferably dimethylformamide), N,N-dialkylacetamides (preferably dimethylacetamide), cyclic amides (preferably N-methylpyrrolidin-2-one), dialkylsulfoxides (preferably dimethylsulfoxide) or aromatic hydrocarbons (preferably benzene or toluene). Compounds of Formula (4) may be reacted with compounds of Formula (5) (where RC is alkyl (1-6 carbons)) in the presence or absence of an acid in the presence of an inert solvent at temperatures ranging from OOC to 2000C to produce compounds of Formula (6). Acids may include, but are not limited to alkanoic acids of 2 to 10 carbons (preferably acetic acid), haloalkanoic acids (2 - 10 carbons, 1-10 halogens, such as trifluoroacetic acid), arylsulfonic acids (preferably p-toluenesulfonic acid or benzenesulfonic acid), alkanesulfonic acids of 1 to 10 carbons (preferably methanesulfonic acid), hydrochloric acid, sulfuric acid or phosphoric acid. Stoichiometric or catalytic amounts of such acids may be used. Inert solvents may include, but are not limited to, water, alkanenitriles (1 to 6 carbons, preferably acetonitrile) , halocarbons of 1 to 6 carbons and 1 to 6 halogens (preferably dichloromethane or chloroform), alkyl alcohols of 1 to 10 carbons (preferably ethanol) 1 dialkyl ethers (4 to 12 carbons, preferably diethyl ether or di-isopropylether) or cyclic ethers such as dioxan or tetrahydrofuran. Preferred temperatures range from ambient temprature to 1000C. Compounds of Formula (6) may be converted to intermediate compounds of Formula (7) by treatment with compounds C=Y(Rd)2 (where Y is O or S and Rd is halogen (preferably chlorine), alkoxy (1 to 4 carbons) or alkylthio (1 to 4 carbons)) in the presence or absence of a base in an inert solvent at reaction temperatures from -50 C to 2000C. Bases may include, but are not limited to, alkali metal hydrides (preferably sodium hydride), alkali metal alkoxides (1 to 6 carbons) (preferably sodium methoxide or sodium ethoxide), alkali metal carbonates, alkali metal hydroxides, trialkyl amines (preferably N,N-diisopropyl-N-ethyl amine or triethylamine) or aromatic amines (preferably pyridine). Inert solvents may include, but are not limited to, alkyl alcohols (1 to 8 carbons, preferably methanol or ethanol), lower alkanenitriles (1 to 6 carbons, preferably acetonitrile), cyclic ethers (preferably tetrahydrofuran or 1,4-dioxane), N,N-dialkylformamides (preferably dimethylformamide), N,N-dialkylacetamides (preferably dimethylacetamide), cyclic amides (preferably Nmethylpyrrolidin-2-one), dialkylsulfoxides (preferably dimethylsulfoxide) or aromatic hydrocarbons (preferably benzene or toluene) . Preferred temperatures are OOC to 1500C. Intermediate compounds of Formula (7), where Z is N, may be synthesized according the methods outlined in Scheme 5. SCHEME 5 EMI75.1 <tb> <SEP> N <SEP> <tb> <SEP> RH2N3, <SEP> base, <SEP> <SEP> / <SEP> reducing <SEP> agent, <tb> ArCH2CN <SEP> solvent <SEP> H2N <SEP> solvent <tb> <SEP> Ar <tb> <SEP> NH <tb> <SEP> R1/ <tb> <SEP> R1 <SEP> - <SEP> % <SEP> solvent <SEP> (5) <SEP> OR <tb> H,N/" <SEP> + <SEP> / <SEP> - <SEP> acid1 <tb> <SEP> solvent <SEP> NH <SEP> HN <tb> H2N <SEP> RlNN <tb> <SEP> Ar <SEP> H <tb> <SEP> (10) <SEP> Ar <SEP> H <SEP> Ar <tb> <SEP> (11) <tb> <SEP> Y <tb> <SEP> y=C(Rd)2, <SEP> base, <SEP> HN <SEP> N <SEP> ¯ <tb> <SEP> solven <SEP> s <SEP> < <SEP> X <tb> <SEP> Ar <tb> (7) Y = O, S; Z N Compounds of ArCH2CN are reacted with compounds of Formula RqCH2N3 (where R9 is a phenyl group optionally substituted by H, alkyl (1 to 6 carbons) or alkoxy (1 to 6 carbons) in the presence or absence of a base in an inert solvent at temperatures ranging from 0 C to 200 C to generate compounds of Formula (9). Bases may include, but are not limited to, alkali metal hydrides (preferably sodium hydride), alkali metal alkoxides (1 to 6 carbons) (preferably sodium methoxide, sodium ethoxide or potassium t-butoxide), alkaline earth metal hydrides, alkali metal dialkylamides (preferably lithium di-isopropylamide), alkali metal carbonates, alkali metal hydroxides, alkali metal bis(trialkylsilyl)amides (preferably sodium bis(trimethylsilyl)amide), trialkyl amines (preferably N, N-di-isopropyl-N-ethyl amine or triethylamine) or aromatic amines (preferably pyridine). Inert solvents may include, but are not limited to, alkyl alcohols (1 to 8 carbons, preferably methanol or ethanol), lower alkanenitriles (1 to 6 carbons1 preferably acetonitrile), dialkyl ethers (preferably diethyl ether), cyclic ethers (preferably tetrahydrofuran or 1,4-dioxane), N,N-dialkylformamides (preferably dimethylformamide), N,N-dialkylacetamides (preferably dimethylacetamide), cyclic amides (preferably N-methylpyrr5lidin-2-one), dialkylsulfoxides (preferably dimethylsulfoxide) or aromatic hydrocarbons (preferably benzene or toluene) . Preferred reaction temperatures range from ambient temperature to 1000C. Compounds of Formula (9) may be treated with a reducing agent in an inert solvent at -1000C to 1000C to afford products of Formula (10). Reducing agents include, but are not limited to, (a) hydrogen gas in combination with noble metal catalysts such as Pd-oncarbon, Pt02, Pt-on-carbon, Rh-on-alumina or Raney nickel, (b) alkali metals (preferably sodium) in combination with liquid ammonia or (c) ceric ammonium nitrate. Inert solvents may include, but are not limited to, alkyl alcohols (1 to 8 carbons, preferably methanol or ethanol), lower alkanenitriles (1 to 6 carbons, preferably acetonitrile), water, dialkyl ethers (preferably diethyl ether), cyclic ethers (preferably tetrahydrofuran or 1,4-dioxane), N,N-dialkylformamides (preferably dimethylformamide), N,N-dialkylacetamides (preferably dimethylacetamide), cyclic amides (preferably N-methylpyrrolidin-2-one), dialkylsulfoxides (preferably dimethylsulfoxide) or aromatic hydrocarbons (preferably benzene or toluene) The preferred reaction temperatures are -50 C to 600C. Compounds of Formula (9) are then converted to compounds of Formula (7) (where Z is N) via intermediates of Formula (11) using the reagents and reaction conditions outlined in Scheme 4 for the conversion of compounds of Formula (4) to compounds of Formula (,) (where Z is Cur2) Compounds of Formula (1) may also be prepared from compounds of Formula (7) (where Y is O, S and Z is defined above) as outlined in Scheme 6: SCHEME 6 EMI77.1 <tb> <SEP> Y <SEP> R3S, <SEP> + <SEP> / <SEP> - <SEP> acid, <SEP> R3 <tb> <SEP> YN <SEP> / <SEP> - <SEP> dehydrating <SEP> agent <tb> <SEP> HN' <SEP> N <SEP> 9 <SEP> + <SEP> / <SEP> - <SEP> solvent <SEP> l <SEP> S <tb> R1 <tb> <SEP> Ar <SEP> R1N <SEP> Ar <tb> (7) Y = O, S; Z = N, CR2 (1) A = N Compounds of Formula (7) may be reacted with compounds of Formula R3H in the presence of a dehydrating agent in an inert solvent at reaction t alkyl alcohols (1 to 8 carbons1 preferably methanol or ethanol)1 lower alkanenitriles (1 to 6 carbons, preferably acetonitrile), dialkyl ethers (preferably glyme or diglyme), cyclic ethers (preferably tetrahydrofuran or 1,4-dioxane), N,N-dialkylformamides (preferably dimethylformamide), N,N-dialkylacetamides (preferably dimethylacetamide), cyclic amides (preferably N-methylpyrrolidin-2-one), dialkylsulfoxides (preferably dimethylsulfoxide) , aromatic hydrocarbons (preferably benzene or toluene) or halocarbons of 1 to 10 carbons and 1 to 10 halogens (preferably chloroform). Preferred reaction temperatures range from ambient temperature to 1500C. Some compounds of Formula (1) (where A is N) may also be prepared by the methods shown in Scheme 7: SCHEME 7 EMI78.1 <tb> <SEP> R3C(ORe)3, <SEP> R3 <tb> <SEP> NH <SEP> HN'N <SEP> + <SEP> / <SEP> - <SEP> acid, <SEP> l <tb> <SEP> solvent <SEP> l <tb> R1 <SEP> NH <tb> <SEP> Ar <SEP> R1 <SEP> N <tb> <SEP> (14) <SEP> Ar <tb> (1) A = N Intermediate compounds of Formula (14), where Z is defined above, may be reacted with compounds of Formula R3C(ORe)3, where Re may be alkyl (1 to 6 carbons) in the presence or absence of an acid in an inert solvent at temperatures ranging from OOC to 2500C. Acids may include, but are not limited to alkanoic acids of 2 to 10 carbons (preferably acetic acid), arylsulfonic acids (preferably p-toluenesulfonic acid or benzenesulfonic acid), alkanesulfonic acids of 1 to 10 carbons (preferably methanesulfonic acid), hydrochloric acid, sulfuric acid or phosphoric acid. Stoichiometric or catalytic amounts of such acids may be used. Inert solvents may include, but are not limited to, lower alkanenitriles (1 to 6 carbons, preferably acetonitrile), dialkyl ethers (preferably diethyl ether), cyclic ethers (preferably tetrahydrofuran or 1,4-dioxane), N,N-dialkylformamides (preferably dimethylformamide), N,N-dialkylacetamides (preferably dimethylacetamide), cyclic amides (preferably Nmethylpyrrolidin-2-one), dialkylsulfoxides (preferably dimethylsulfoxide), aromatic hydrocarbons (preferably benzene or toluene) or haloalkanes of 1 to 10 carbons and 1 to 10 halogens (preferably dichloromethane). Preferred reaction temperatures range from 500C to 1500C. Intermediate compounds of Formula (7) may also be synthesized by the reactions displayed in Scheme 8. * SCHEME 8 EMI79.1 <SEP> Y <tb> <SEP> Air <tb> <SEP> < <SEP> < z <SEP> z <SEP> Zltbl, <SEP> + <SEP> / <SEP> - <SEP> catalyst, <tb> <SEP> rolvnt <SEP> ArM, <SEP> + <SEP> solvent <SEP> ANN\\ <tb> (15) <SEP> Y <SEP> = <SEP> OH, <SEP> SH <SEP> R1¸N·%Z <tb> <SEP> Ar <tb> <SEP> NR6R7; <tb> Z = N, CR2, X = Br, C1, I, B(OR"")2 (7) A = N Compounds of Formula (15), (where Y is OH, SH, NR6R7; Z is defined above, X is Br, Cl, I, 03SCF3 or B(OR"")2 and R"" is H or alkyl (1 to 6 carbons)) may be reacted with a compound of Formula ArM (where M is halogen, alkali metal, ZnCl, ZnBr, ZnI, MgBr, MgOl1 MgI, CeCl2, CeBr2 or copper halides) in the presence or absence of an organometallic catalyst in the presence or absence of a base in an inert solvents at temperatures ranging from -1000C to 2000C. Those skilled in the art will recognize that the reagents ArM may be generated in situ. Organometallic catalysts include, but are not limited to, palladium phosphine complexes (such as Pd(PPh3)4), palladium halides or alkanoates (such as PdC12(PPh3)2 or Pd(OAc)2) or nickel complexes (such as NiC12(PPh3)2). Bases may include, but are not limited to, alkali metal carbonates or trialkyl amines (preferably N,N-di-isopropyl-N-ethyl amine or triethylamine) . Inert solvents may include, but are not limited to, dialkyl ethers (preferably diethyl ether)1 cyclic ethers (preferably tetrahydrofuran or 1,4dioxane), N,N-dialkylformamides (preferably dimethylformamide), N,N-dialkylacetamides (preferably dimethylacetamide), cyclic amides (preferably Nmethylpyrrolidin-2-one), dialkylsulfoxides (preferably dimethylsulfoxide), aromatic hydrocarbons (preferably benzene or toluene) or water. Preferred reaction temperatures range from -800C to 1000C. The choices of M and X are known to those skilled in the art (cf. Imamoto, T., Organocerium Reagents in Comprehensive Organic Synthesis, Trost, B.M. ed., (Elmsford, NY: Pergamon Press, 1991), 1, 231-250; Knochel, P., Organozinc, Organocadmium and Organomercury Reagents in Comprehensive Oraanic Synthesis, Trost, B.M. ed., (Elmsford, NY: Pergamon Press, 1991), 1, 211-230; Knight, D.W., Coupling Reactions between sp2 Carbon Centers, in Comprehensive Oraanic Synthesis, Trost, B.M. ed., (Elmsford, NY: Pergamon Press, 1991), 3, 481-520). Compounds of Formula (1) may also be prepared using the methods shown in Scheme 9. SC1;M Q EMI81.1 <tb> <SEP> R3 <tb> <SEP> R3 <tb> <SEP> A <SEP> R3 <tb> <SEP> ArM, <SEP> + <SEP> / <SEP> - <SEP> catalyst, <SEP> A¸,/N <tb> R1X%N <SEP> /9 <SEP> solvent <SEP> RlX%NJf <tb> <SEP> R1 <tb> <SEP> x <SEP> N <tb> <SEP> Ar <tb> <SEP> (16) <SEP> X <SEP> = <SEP> Br, <SEP> C1, <SEP> I, <SEP> (1) <tb> <SEP> B <SEP> ( <SEP> OR <SEP> " <SEP> " <SEP> 03SCF9 <tb> Compounds of Formula (16), where A, Z, R1 and R3 are defined above and X is Br, C1, I, 03SCF3 or B(OR"")2 and R"" is H or alkyl (1 to 6 carbons)) may be reacted with a compound of Formula ArM (where M is halogen, alkali metal1 ZnCl, ZnBr, ZnI, MgBr, MgCl, MgI, CeC12, CeBr2 or copper halides) in the presence or absence of an organometallic catalyst in the presence or absence of a base in an inert solvents at temperatures ranging from -100 C to 200 C. Those skilled in the art will recognize that the reagents ArM may be generated in situ (see the above references in Comprehensive Organic Synthesis). Organometallic catalysts include, but are not limited to, palladium phosphine complexes (such as Pd(PPh3)4), palladium halides or alkanoates (such as PdC12(PPh3)2 or Pd(OAc)2) or nickel complexes (such as NiC12(PPh3)2). Bases may include, but are not limited to, alkali metal carbonates or trialkyl amines (preferably N,N-di-isopropyl-N-ethyl amine or triethylamine). Inert solvents may include, but are not limited to, dialkyl ethers (preferably diethyl ether), cyclic ethers (preferably tetrahydrofuran or 1,4dioxane), N,N-dialkylformamides (preferably dimethylformamide), N,N-dialkylacetamides (preferably dimethylacetamide), cyclic amides (preferably Nmethylpyrrolidin-2-one), dialkylsulfoxides (preferably dimethylsulfoxide), aromatic hydrocarbons (preferably benzene or toluene) or water. Preferred reaction temperatures range from -80 C to 100 C. Intermediate compounds of Formula (7)(where Y is O, S, NH, Z is CR2 and RÚ, R2 and Ar are defined as above) may be prepared as illustrated in Scheme 10. SCHEME 10 EMI82.1 <tb> <SEP> Y <tb> <SEP> 0 <SEP> HZNK <SEP> N'N <tb> NH2NH2(C=Y)NH2 <SEP> acid, <SEP> | <SEP> zR2 <tb> NR2 <SEP> + <SEP> / <SEP> - <SEP> base <SEP> or <SEP> acid, <SEP> "' <tb> <SEP> solvent <SEP> acid, <tb> <SEP> Ar <SEP> Ar <tb> <SEP> at(3) <SEP> (17) <tb> <SEP> R1C <SEP> (OR')sr <SEP> X <tb> <SEP> + <SEP> / <SEP> - <SEP> acid1 <SEP> RN <tb> <SEP> solvent <tb> <SEP> R1 <SEP> N <tb> <SEP> Ar <tb> (7) Y = O, S, NH; Z = CR2, Compounds of Formula (3) may be reacted with compounds of Formula H2NNH(C=Y)NH2, where Y is O, S or NH, in the presence or absence of a base or acid in an inert solvent at temperatures from OOC to 250 C to produce compounds of Formula (17). Acids may include, but are not limited to alkanoic acids of 2 to 10 carbons (preferably acetic acid), arylsulfonic acids (preferably p-toluenesulfonic acid or benzenesulfonic acid), alkanesulfonic acids of 1 to 10 carbons (preferably methanesulfonic acid), hydrochloric acid, sulfuric acid or phosphoric acid. Stoichiometric or catalytic amounts of such acids may be used. Bases may include, but are not limited to, alkali metal hydrides (preferably sodium hydride)1 alkali metal alkoxides (1 to 6 carbons) (preferably sodium methoxide or sodium ethoxide)1 alkaline earth metal hydrides, alkali metal dialkylamides (preferably lithium di-isopropylamide), alkali metal bis(trialkylsilyl)amides (preferably sodium bis(trimethylsilyl)amide), trialkyl amines (preferably N,N-di-isopropyl-N-ethyl amine or triethylamine) or aromatic amines (preferably pyridine). Inert solvents may include, but are not limited to, alkyl alcohols (1 to 6 carbons), lower alkanenitriles (1 to 6 carbons, preferably acetonitrile), dialkyl ethers (preferably diethyl ether), cyclic ethers (preferably tetrahydrofuran or 1,4-dioxane), N,N-dialkylformamides (preferably dimethylformamide), N, N-dialkylacetamides (preferably dimethylacetamide), cyclic amides (preferably N-methylpyrrolidin-2-one), dialkylsulfoxides (preferably dimethylsulfoxide), aromatic hydrocarbons (preferably benzene or toluene) or haloalkanes of 1 to 10 carbons and 1 to 10 halogens (preferably dichloromethane). Preferred reaction temperatures range from OOC to 1500C. Compounds of Formula (17) may then be reacted with compounds of Formula R3C(ORe)3, where Re may be alkyl (1 to 6 carbons) in the presence or absence of an acid in an inert solvent at temperatures ranging from OOC to 2500C. Acids may include, but are not limited to alkanoic acids of 2 to 10 carbons (preferably acetic acid), arylsulfonic acids (preferably p-toluenesulfonic acid or benzenesulfonic acid), alkanesulfonic acids of 1 to 10 carbons (preferably methanesulfonic acid), hydrochloric acid, sulfuric acid or phosphoric acid. Stoichiometric or catalytic amounts of such acids may be used. Inert solvents may include, but are not limited to, lower alkanenitriles (1 to 6 carbons, preferably acetonitrile), dialkyl ethers (preferably diethyl ether), cyclic ethers (preferably tetrahydrofuran or 1,4-dioxane), N,N-dialkylformamides (preferably dimethylformamide), N,N-dialkylacetamides (preferably dimethylacetamide), cyclic amides (preferably Nmethylpyrrolidin-2-one), dialkylsulfoxides (preferably dimethylsulfoxide), aromatic hydrocarbons (preferably benzene or toluene) or haloalkanes of 1 to 10 carbons and 1 to 10 halogens (preferably dichloromethane). Preferred reaction temperatures range from 50 C to 150 C. In Scheme 11, the procedures which may be used to convert compounds of Formula (1), where R3 is CoR7, Co2R7, NR8COR7 and CONR6R7, to other compounds of Formula (1), where R3 is CH(OH)R7, CH2OH, NR8CH2R7 and CH2NR6R7 by treatment with a reducing agent in an inert solvent at temperatures ranging from -80 C to 250 C. SCRE 11 EMI84.1 <tb> <SEP> R3 <tb> <SEP> R3 <tb> <SEP> ANN\\ <SEP> reducing <SEP> agent, <tb> <SEP> N <SEP> , <SEP> solvsnt <SEP> A <SEP> N' <tb> R1N&num;(Z <SEP> R1h'i <tb> <SEP> Ar <SEP> R <SEP> l¹N·Z <tb> (1) R = COR7, CO2R7, CONR6R7 (1) R3 = C(oH)R7, CH2OH, CH2NR6R7 Reducing agents include, but are not limited to, alkali metal or alkaline earth metal borohydrides (preferably lithium or sodium borohydride), borane, dialkylboranes (such as di-isoamylborane), alkali metal aluminum hydrides (preferably lithium aluminum hydride), alkali metal (trialkoxy)aluminum hydrides, or dialkyl aluminum hydrides (such as di-isobutylaluminum hydride) . Inert solvents may include, but are not limited to, alkyl alcohols (1 to 6 carbons), dialkyl ethers (preferably diethyl ether) I cyclic ethers (preferably tetrahydrofuran or 1,4-dioxane), aromatic hydrocarbons (preferably benzene or toluene). Preferred reaction temperatures range from -80 C to 100 C. In Scheme 12, the procedures are shown which may be used to convert compounds of Formula (1), where R3 is COR7 or CO2R7, to other compounds of Formula (1), where R3 is C(OH)(R7)2 by treatment with a reagent of Formula R7M in an inert solvent at temperatures ranging from -80 C to 250 C. SCHEME 12 EMI85.1 <tb> <SEP> R3 <SEP> R3 <tb> <SEP> R3 <tb> <SEP> AYNN\\ <SEP> reducing <SEP> agent1 <SEP> > <SEP> N <tb> <SEP> AIZ <SEP> solvent <tb> R1 <SEP> / <SEP> N <SEP> t <SEP> R1 <SEP> < <SEP> N <SEP> 8 <SEP> Z <tb> <SEP> Ar <tb> <SEP> Ar <tb> <SEP> (1) <SEP> R3 <SEP> = <SEP> CoR7, <SEP> C02R71 <SEP> (1) <SEP> R3 <SEP> = <SEP> C(OH)(R7)2 <tb> M is halogen, alkali metal, ZnCl, ZnBr, ZnI, MgBr, MgCl1 MgI, CeC12, CeBr2 or copper halides. Inert solvents may include, but are not limited to, dialkyl ethers (preferably diethyl ether), cyclic ethers (preferably tetrahydrofuran) or aromatic hydrocarbons (preferably benzene or toluene). Preferred reaction temperatures range from -80 C to 100 C Compounds of Formula (1), where R3 may be -NR8COR7, -N(COR7)2, -NR8CONR6R7, -NR8CO2R13, -NR6R7 -NR8SO2R7, may be synthesized as depicted in Scheme 13. SCHEME 13 EMI86.1 <tb> <SEP> 0 <tb> <SEP> NC <SEP> X <SEP> R1 <SEP> NH2 <tb> (lB)R <SEP> + <SEP> I <SEP> - <SEP> base, <SEP> R <SEP> NN <tb> <SEP> + <SEP> solvent <SEP> / <SEP> | <SEP> Z <tb> <SEP> N <SEP> ' <SEP> N <SEP> R1 <tb> <SEP> HN\\z <SEP> Ar <tb> <SEP> Z <tb> <SEP> (19) <tb> <SEP> H2N <tb> <SEP> Ar <tb> <SEP> (4) <SEP> Z <SEP> = <SEP> CR2 <tb> (10) <SEP> Z <SEP> = <SEP> N <tb> <SEP> R3 <tb> alkylating, <SEP> sulfonylating <tb> or <SEP> acylating <SEP> agents <SEP> 4 <SEP> N <tb> + <SEP> / <SEP> - <SEP> base, <SEP> solvent <SEP> N <tb> <SEP> R1' <tb> <SEP> Ar <tb> <SEP> Ar <tb> <SEP> (1) <tb> <SEP> A <SEP> = <SEP> CR <tb> <SEP> R3 <SEP> =NR6R7, <SEP> NR8CoR7, <tb> <SEP> N(COR7 <SEP> )2I <tb> <SEP> NR8CONR6R7, <tb> <SEP> NR8C02R13 <tb> Reaction of compounds of Formula (18), where R and R1 are defined above, with compounds of Formula (4) or (10) in the presence or absence of base in an inert solvent may produce compounds of Formula (19) at temperatures ranging from -50 C to 250 C. Bases may include, but are not limited to, alkali metal hydrides (preferably sodium hydride), alkali metal alkoxides (1 to 6 carbons) (preferably sodium methoxide or sodium ethoxide), alkaline earth metal hydrides, alkali metal dialkylamides (preferably lithium di-isopropylamide) alkali metal carbonates, alkali metal bis(trialkylsilyl)amides (preferably sodium bis(trimethylsilyl)amide), trialkyl amines (prefereably di-isopropylethyl amine) or aromatic amines (preferably pyridine). Inert solvents may include, but are not limited to, alkyl alcohols (1 to 8 carbons, preferably methanol or ethanol) 1 lower alkanenitriles (1 to 6 carbons, preferably acetonitrile), dialkyl ethers (preferably diethyl ether), cyclic ethers (preferably tetrahydrofuran or 1,4-dioxane), N,N-dialkylformamides (preferably dimethylformamide), N,N-dialkylacetamides (preferably dimethylacetamide), cyclic amides (preferably N-methylpyrrolidin-2-one), dialkylsulfoxides (preferably dimethylsulfoxide) or aromatic hydrocarbons (preferably benzene or toluene). Preferred reaction temperatures range from OOC to 1000C. Compounds of Formula (19) may then be reacted with alkylating agents, sulfonylating agents or acylating agents or sequential reactions with combinations thereof, in the presence or absence of a base in an inert solvent at reaction temperatures ranging from -800C to 250 C may afford compounds of Formula (1), where R3 may be -NR8COR7, -N(CoR7)2, -NR8CONR6R7, -NR8C02R13 -NR6R7 -NR8SO2R7. Alkylating agents may include, but are not limited to, Cl-Clo alkyl -halides1 -tosylates, -mesylates or -triflates; Cl-Clo haloalkyl(l - 10 halogens)-halides, -tosylates, -mesylates or -triflates; C2-Cg alkoxyalkyl-halides, -tosylates, -mesylates or -triflates; C3-C6 cycloalkyl-halides, -tosylates, -mesylates or -triflates; 04- C12 cycloalkylalkyl-halides, -tosylates, -mesylates or -triflates; aryl(C1-C4 alkyl)-halides, -tosylates, -mesylates or -triflates; heteroaryl(C1-Cg alkyl)halides, -tosylates, -mesylates or -triflates; or heterocyclyl(C1-C4 alkyl)-halides, -tosylates, -mesylates or -triflates. Acylating agents may include, but are not limited to, C1-C10 alkanoyl halides or anhydrides, C1-C10 haloalkanoyl halides or anhydrides wiWh 1 - 10 halogens1 C2-Cg alkoxyalkanoyl halides or anhydrides, C3-C6 cycloalkanoyl halides or anhydrides, C4-C12 cycloalkylalkanoyl halides or anhydrides, aroyl halides or anhydrides, aryl(C1-C4) alkanoyl halides or anhydrides, heteroaroyl halides or anhydrides, heteroaryl(C1-C4) alkanoyl halides or anhydrides, heterocyclylcarboxylic acid halides or anhydrides or heterocyclyl(Cl-C4) alkanoyl halides or anhydrides. Sulfonylating agents include, but are not limited to, Cl-C 10 alkylsulfonyl halides or anhydrides, C1-C10 haloalkylsulfonyl halides or anhydrides with 1 - 10 halogens1 C2-Cg alkoxyalkylsulfonyl halides or anhydrides, C3-C6 cycloalkylsulfonyl halides or anhydrides, C4-C12 cycloalkylalkylsulfonyl halides or anhydrides, arylsulfonyl halides or anhydrides, aryl(C1 C4 alkyl)-1 heteroarylsulfonyl halides or anhydrides, heteroaryl(C1-Cq alkyl)sulfonyl halides or anhydrides, heterocyclylsulfonyl halides or anhydrides or heterocyclyl(C1-C4 alkyl)sulfonyl halides or anhydrides. Bases may include, but are not limited to, alkali metal hydrides (preferably sodium hydride), alkali metal alkoxides (l to 6 carbons) (preferably sodium methoxide or sodium ethoxide), alkaline earth metal hydrides, alkali metal dialkylamides (preferably lithium diisopropylamide), alkali metal carbonates, alkali metal bis (trialkylsilyl) amides (preferably sodium bis(trimethylsilyl)amide), trialkyl amines (prefereably di-isopropylethyl amine) or aromatic amines (preferably pyridine). Inert solvents may include, but are not limited to, alkyl alcohols (1 to 8 carbons, preferably methanol or ethanol)1 lower alkanenitriles (1 to 6 carbons, preferably acetonitrile), dialkyl ethers (preferably diethyl ether), cyclic ethers (preferably tetrahydrofuran or 1,4-dioxane), N,N-dialkylformamides (preferably dimethylformamide), N,N-dialkylacetamides (preferably dimethylacetamide), cyclic amides (preferably N-methylpyrrolidin-2-one), dialkylsulfoxides (preferably dimethylsulfoxide) or aromatic hydrocarbons (preferably benzene or toluene) . Preferred reaction temperatures range from OOC to 1000C. Compounds of Formula (1), where A is CR and R is defined above, may be synthesized by the methods depicted in Scheme 14. SCHEME 14 EMI90.1 <tb> <SEP> 0 <SEP> 0 <tb> <SEP> R1 <tb> <SEP> HNN\ <SEP> RI <SEP> R3 <tb> <SEP> z <SEP> R <tb> <SEP> H2N <SEP> (20) <SEP> A <SEP> NN\\ <tb> <SEP> + <SEP> / <SEP> z <tb> <SEP> Ar <SEP> solvent <tb> <SEP> (4) <SEP> Z <SEP> = <SEP> CR2 <SEP> R1 <tb> <SEP> (10) <SEP> Z <SEP> = <SEP> N <SEP> (1) <SEP> Ar <tb> <SEP> A <SEP> = <SEP> CR <tb> <SEP> R002 <SEP> R1 <tb> <SEP> R <SEP> R3H, <SEP> + <SEP> I <SEP> - <SEP> base, <tb> <SEP> R <SEP> + <SEP> / <SEP> - <SEP> solvent <tb> <SEP> (21) <tb> <SEP> + <SEP> / <SEP> - <SEP> base, <tb> <SEP> solvent <tb> <SEP> OH <SEP> x <tb> <SEP> hirlognating <SEP> agent <tb> <SEP> T <SEP> Nl <SEP> zz <SEP> or <SEP> sulfonylating <tb> <SEP> base, <SEP> / <SEP> - <SEP> bas, <tb> Rl <SEP> At <SEP> ii <SEP> solvent <SEP> RlNN <tb> <SEP> Ar <SEP> Ar <tb> <SEP> (22) <SEP> (23) <tb> Compounds of Formula (4) or (10) may be treated with compounds of Formula (20), where R1 and R3 are defined above in the presence or absence of base in an inert solvent at temperatures ranging from 0 C to 250 C to give compounds of Formula (1), where A is CR and R is defined above. Bases may include, but are not limited to, alkali metal hydrides (preferably sodium hydride), alkali metal alkoxides (1 to 6 carbons) (preferably sodium methoxide or sodium ethoxide), alkaline earth metal hydrides, alkali metal dialkylamides (preferably lithium di-isopropylamide), alkali metal carbonates, alkali metal bis(trialkylsilyl)amides (preferably sodium bis(trimethylsilyl)amide), trialkyl amines (preferably di-isopropylethyl amine) or aromatic amines (preferably py: idine). Inert solvents may include, but are not limited to, alkyl alcohols (1 to 8 carbons1 preferably methanol or ethanol), lower alkanenitriles (1 to 6 carbons, preferably acetonitrile), dialkyl ethers (preferably diethyl ether), cyclic ethers (preferably tetrahydrofuran or 1,4-dioxane), N,N-dialkylformamides (preferably dimethylformamide), N,N-dialkylacetamides (preferably dimethylacetamide), cyclic amides (preferably N-methylpyrrolidin-2-one), dialkylsulfoxides (preferably dimethylsulfoxide) or aromatic hydrocarbons (preferably benzene or toluene) . Preferred reaction temperatures range from OOC to 1000C. Alternatively, compounds of Formula (1) where A is CR and R is defined above, may be synthesized through intermediates (22) and (23) Compounds of Formula (4) or (10) may be treated with compounds of Formula (21), where R1 is defined above and Re is alkyl (1 - 6 carbons), in the presence or absence of base in an inert solvent at temperatures ranging from OOC to 2500C to give compounds of Formula (1), where A is CR and R is defined above. Bases may include, but are not limited to, alkali metal hydrides (preferably sodium hydride), alkali metal alkoxides (1 to 6 carbons) (preferably sodium methoxide or sodium ethoxide), alkaline earth metal hydrides, alkali metal dialkylamides (preferably lithium di-isopropylamide), alkali metal carbonates, alkali metal bis (trialkylsilyl) amides (preferably sodium bis(trimethylsilyl)amide), trialkyl amines (prefereably di-isopropylethyl amine) or aromatic amines (preferably pyridine). Inert solvents may include, but are not limited to, alkyl alcohols (1 to 8 carbons, preferably methanol or ethanol), lower alkanenitriles (1 to 6 carbons, preferably acetonitrile), dialkyl ethers (preferably diethyl ether)1 cyclic ethers (preferably tetrahydrofuran or 1,4-dioxane), N,N-dialkylformamides (preferably dimethylformamide), N,N-dialkylacetamides (preferably dimethylacetamide), cyclic amides (preferably N-methylpyrrolidin-2-one), dialkylsulfoxides (preferably dimethylsulfoxide) or aromatic hydrocarbons (preferably benzene or toluene) . Preferred reaction temperatures range from OOC to 1000C. Compounds of Formula (22) may be treated with a halogenating agent or sulfonylating agent in the presence or absence of a base in the presence or absence of an inert solvent at reaction temperatures ranging from -80 C to 2500C to give products of Formula (23) (where X is halogen, alkanesulfonyloxy, arylsulfonyloxy or haloalkanesulfonyloxy). Halogenating agents include, but are not limited to, SOC12, POCl3, PCl3, PC15, POBr3, PBr3 or PBr5. Sulfonylating agents include, but are not limited to, alkanesulfonyl halides or anhydrides (such as methanesulfonyl chloride or methanesulfonic acid anhydride), arylsulfonyl halides or anhydrides (such as p-toluenesulfonyl chloride or anhydride) or haloalkylsulfonyl halides or anhydrides (preferably trifluoromethanesulfonic anhydride). Bases may include, but are not limited to, alkali metal hydrides (preferably sodium hydride), alkali metal alkoxides (1 to 6 carbons) (preferably sodium methoxide or sodium ethoxide), alkaline earth metal hydrides, alkali metal dialkylamides (preferably lithium di-isopropylamide), alkali metal bis(trialkylsilyl)amides (preferably sodium bis(trimethylsilyl)amide), trialkyl amines (preferably N,N-di-isopropyl-N-ethyl amine or triethylamine) or aromatic amines (preferably pyridine). Inert solvents may include, but are not limited to, lower alkanenitriles (1 to 6 carbons, preferably acetonitrile), dialkyl ethers (preferably diethyl ether) 1 cyclic ethers (preferably tetrahydrofuran or 1,4-dioxane), N,N-dialkylformamides (preferably dimethylformamide), N, N-dialkylacetamides (preferably dimethylacetamide) , cyclic amides (preferably Nmethylpyrrolidin-2-one), dialkylsulfoxides (preferably dimethylsulfoxide), aromatic hydrocarbons (preferably benzene or toluene) or haloalkanes of 1 to 10 carbons and 1 to 10 halogens (preferably dichloromethane) Preferred reaction temperatures range from -20 C to 1000C. Compounds of Formula (23) may be reacted with compounds of Formula R3H (where R3 is defined as above except R3 is not SH, CoR7, CO2R7, aryl or heteroaryl) in the presence or absence of a base in the presence or absence of an inert solvent at reaction temperatures ranging from -80 C to 2500C to generate compounds of Formula (1). Bases may include, but are not limited to, alkali metal hydrides (preferably sodium hydride), alkali metal alkoxides (1 to 6 carbons) (preferably sodium methoxide or sodium ethoxide) I alkaline earth metal hydrides, alkali metal dialkylamides (preferably lithium di-isopropylamide), alkali metal carbonates, alkali metal bicarbonates, alkali metal bis (trialkylsilyl) amides (preferably sodium bis(trimethylsilyl)amide), trialkyl amines (preferably N,N-di-isopropyl-N-ethyl amine) or aromatic amines (preferably pyridine). Inert solvents may include, but are not limited to, alkyl alcohols (1 to 8 carbons, preferably methanol or ethanol), lower alkanenitriles (l to 6 carbons, preferably acetonitrile), dialkyl ethers (preferably diethyl ether), cyclic ethers (preferably tetrahydrofuran or 1,4-dioxane), N,N-dialkylformamides (preferably dimethylformamide), N,N-dialkylacetamides (preferably dimethylacetamide) , cyclic amides (preferably N-methylpyrrolidin-2-one), dialkylsulfoxides (preferably dimethylsulfoxide), aromatic hydrocarbons (preferably benzene or toluene) or haloalkanes of 1 to 10 carbons and 1 to 10 halogens (preferably dichloromethane). Preferred reaction temperatures range from OOC to 1400C. Some compounds of Formula (1) may also be prepared using the methods shown in Scheme 15. SCHEME 15 EMI95.1 <tb> <SEP> 0 <tb> <SEP> RcO' <SEP> Y <tb> <SEP> NH2NH2, <SEP> Ar <SEP> NH2NH <SEP> (OzY) <SEP> NH2, <tb> <SEP> NB2NE2 <SEP> fezN8 <SEP> acid, <SEP> (24) <SEP> + <SEP> NB2 <SEP> f <tb> <SEP> solvent <SEP> solvent <tb> <SEP> Lurt <tb> <SEP> 9 <SEP> OOH <SEP> H2N <SEP> OH <tb> <SEP> H2 <SEP> N <SEP> Ar <SEP> Ja <tb> <SEP> Ar <tb> <SEP> (26)Y <SEP> = <SEP> O, <SEP> S <tb> <SEP> (26)Y <SEP> = <SEP> O, <SEP> S <tb> For <SEP> A <SEP> = <SEP> N: <SEP> For <SEP> A <SEP> 3 <SEP> CR: <tb> 1) <SEP> R1c(=NN)o <SEP> 1) <SEP> R1 <SEP> (C=O) <SEP> CXtR <SEP> (CaY) <SEP> ORs <SEP> / <tb> +/- <SEP> acid, <SEP> solvent <SEP> +/- <SEP> base <SEP> or <SEP> acid, <tb> 2) <SEP> Y=C(Rd)2 <SEP> solvent <tb> +/- <SEP> base, <SEP> solvent <tb> <SEP> R1(ORa) <tb> <SEP> +/- <SEP> solvent <tb> <SEP> R <SEP> / <SEP> + <SEP> /- <SEP> olv-nt <tb> <SEP> / <tb> <SEP> A <SEP> NN\ <SEP> see <SEP> text <SEP> ANN\\ <tb> <SEP> R1 <SEP> 1 <SEP> R <SEP> R1 <SEP> < X <tb> <SEP> Ar <SEP> Ar <tb> <SEP> ( <SEP> 27)Y <SEP> = <SEP> O, <SEP> S <SEP> (1) <SEP> 2 <SEP> = <SEP> CR2 <tb> A compound of Formula (24) (Ra is a lower alkyl group and Ar is defined as above) may be reacted with hydrazine in the presence or absence of an inert solvent to afford an intermediate of Formula (25), where Ar is defined as above. The conditions employed are similar to those used for the preparation of intermediate of Formula (4) from compound of Formula (3) in Scheme 4. Compounds of Formula (25), where A is N, may be reacted with reagents of the formula R10(=NH)ORe, where R1 is defined above and Re is a lower alkyl group) in the presence or absence of an acid in an inert solvent, followed by reaction with a compound of formula YisC(Rd)2 (where Y is O or S and Rd is halogen (preferably chlorine), alkoxy (1 to 4 carbons) or alkylthio (1 to 4 carbons)) in the presence or absence of a base in an inert solvent to give compounds of Formula (27) (where A is N and Y is 0, S) . The conditions for these transformations are the same as those employed for the conversions of compound of Formula (4) to compound of Formula (7) in Scheme 4. Alternatively, compounds of Formula (25), where A is CR, may be reacted with compounds of the formula R1(C=O)CHR(C=Y)ORc (where R1 and R are defined as above and Rc is a lower alkyl group) to give a compound of Formula (27) (where A is CR) using conditions similar to those employed for the conversion of compounds of Formula (21) to compounds of Formula (22) in Scheme 14. Intermediates of Formula (27) (where Y is 0) may be treated with halogenating agents or sulfonylating agents in the presence or absence of a base in an inert solvent1 followed by reaction with R3H or R2H in the presence or absence of a base in an inert solvent to give compounds of Formula (1) (where Z is CR2) It will be recognized by those skilled in the art that various combinations of halogenating agents1 sulfonylating agents1 R3H or R2H may be used in different orders of reaction sequences in Scheme 15 to afford compounds of Formula (1). For example, in some cases, it may be desirable to react compounds with stoichiometric amounts of halogenating agents or sulfonylating agents, react with R2H (or R3H), then repeat the reaction with halogenating agents or sulfonylating agents and react with R3H (or R2H) to give compounds of Formula (1). The reaction conditions and reagents used for these conversions are similar to the ones employed for the conversion of intermediate compounds of Formulae (22) to (23) to (1) in Scheme 14 (for A is CR) or the conversion of intermediate compounds of Formulae (7) to (8) to (1) in Scheme 1 (where A is N). Alternatively, compounds of Formula (27) (where Y is S) may be converted to compounds of Formula (1) in Scheme 15. Intermediate compounds of Formula (27) may be alkylated with a compound RfX (where Rf is lower alkyl and X is halogen, alkanesulfonyloxy or haloalkanesulfonyloxy) in an inert solvent, (then optionally oxidized with an oxidizing agent in an inert solvent) and then reacted with R3H in the presence or absence of a base in an inert solvent to give a compound of Formula (1). The conditions and reagents employed are similar to those used in the conversion of intermediate compounds of Formulae (7) to (12) (or to (13)) to compounds of Formula (1) in Scheme 2. Compounds of Formula (1) may be prepared from compounds of Formula (24), using an alternate route as depicted in Scheme 15. Compounds of Formula (24) may be converted to compounds of Formula (27) via reaction with compounds of formula NH2NH(C=NH)NH2 in the presence or absence of an acid in an inert solvent, followed by reaction with compounds R1C(ORc)3 (where Rc is lower alkyl and R1 is defined as above), using the conditions employed for the conversion of compounds of Formulae (3) to (17) to (7) in Scheme 10. Some compounds of Formula (2) may be prepared by the methods illustrated in Scheme 16. SCHEME 16 EMI98.1 <tb> <SEP> ya <SEP> YH <tb> <SEP> R14X, <SEP> +1- <SEP> base <SEP> 14 <tb> )= <SEP> solvent <SEP> < 4 <SEP> '"t <SEP> O <tb> <SEP> Ar <SEP> Ar <tb> <SEP> ( <SEP> 27b) <SEP> Y <SEP> = <SEP> O, <SEP> S <SEP> ( <SEP> 28)Y <SEP> = <SEP> O, <SEP> S <tb> <SEP> see <SEP> text <tb> <SEP> R14X, <SEP> R3 <tb> <SEP> sol\ <SEP> iKX <SEP> base, <SEP> b <SEP> e <tb> <SEP> solvent <SEP> 0 <tb> <SEP> R1 <SEP> R1 <tb> <SEP> Ar <SEP> Ar <tb> <SEP> (1) <SEP> Z <SEP> = <SEP> COR <SEP> (2) <tb> Compounds of Formula (27b) may be treated with various alkylating agents R14X (where R14 is defined above and X is halogen, alkanesulfonyloxy or haloalkanesulfonyloxy) in the presence or absence of a base in an inert solvent to afford structures of Formula (28). Compounds of Formula (28) (Y is 0) may then be converted to compounds of Formula (2) by treatment with halogenating agents or sulfonylating agents in the presence or absence of a base in an inert solvent, followed by reaction with R3H in the presence or absence of a base in an inert solvent to give compounds of Formula (2). The reaction conditions used for these conversions are similar to the ones employed for the conversion of intermediate compounds (22) to (23) to (1) in Scheme 14 (for A is CR) or the conversion of intermediate compounds of Formulae (7) to (8) to (1) in Scheme 1 (where A is N). Alternatively, compounds of Formula (28) (Y is S) may be alkylated with a compound RfX (where Rf is lower alkyl and X is halogen, alkanesulfonyloxy or haloalkanesulfonyloxy) in an inert solvent, (then optionally oxidized with an oxidizing agent in an inert solvent) and then reacted with R3H in the presence or absence of a base in an inert solvent to give a compound of Formula (1). The conditions and reagents employed are similar to those used in the conversion of intermediate compounds of Formulae (7) to (12) (or to (13)) to compounds of Formula (1) in Scheme 2. Compounds of Formula (1), where Z is COH, may be converted to compounds of Formula (2) as illustrated in Scheme 16. Treatment with various alkylating agents R14X (where R14 is defined above and X is halogen, alkanesulfonyloxy or haloalkanesulfonyloxy) in the presence or absence of a base in an inert solvent to afford structures (2). It will be recognized by one skilled in the art that the methods used in Scheme 16 may also be used to prepare compounds of Formula (1) where Z is CoR7. For Scheme 16, the terms "base" and " inert solvent" may have the meanings given below. Bases may include, but are not limited to, alkali metal hydrides (preferably sodium hydride), alkali metal alkoxides (1 to 6 carbons) (preferably sodium methoxide or sodium ethoxide), alkaline earth metal hydrides1 alkali metal dialkylamides (preferably lithium di-isopropylamide), alkali metal bis(trialkylsilyl)amides (preferably sodium bis (trimethylsilyl)amide) I trialkyl amines (preferably N,N-di-isopropyl-N-ethyl amine or triethylamine) or aromatic amines (preferably pyridine). Inert solvents may include, but are not limited to, lower alkanenitriles (1 to 6 carbons, preferably acetonitrile), dialkyl ethers (preferably diethyl ether) I cyclic ethers (preferably tetrahydrofuran or 1,4-dioxane), N,N-dialkylformamides (preferably dimethylformamide) , N,N-dialkylacetamides (preferably dimethylacetamide), cyclic amides (preferably Nmethylpyrrolidin-2-one), dialkylsulfoxides (preferably direthylsulfoxide), aromatic hydrocarbons (preferably benzene or toluene) or haloalkanes of 1 to 10 carbons and 1 to 10 halogens (preferably dichloromethane). Preferred reaction temperatures range from -200C to 1000C. EXAMPLES Analytical data were recorded for the compounds described below using the following general procedures. Proton NMR spectra were recorded on an IBM-Bruker FT-NMR (300 MHz); chemical shifts were recorded in ppm (8) from an internal tetramethysilane standard in deuterochloroform or deuterodimethylsulfoxide as specified below. Mass spectra (MS) or high resolution mass spectra (HRMS) were recorded on a Finnegan MAT 8230 spectrometer (using chemi-ionization (CI) with NH3 as the carrier gas or gas chromatography (GC) as specified below) or a Hewlett Packard 5988A model spectrometer. Melting points were recorded on a Buchi Model 510 melting point apparatus and are uncorrected. Boiling points are uncorrected. All pH determinations during workup were made with indicator paper. Reagents were purchased from commercial sources and, where necessary, purified prior to use according to the general procedures outlined by D. Perrin and W.L.F. Armarego, Purification of Laboratory Chemicals, 3rd ed., (New York: Pergamon Press, 1988) . Chromatography was performed on silica gel using the solvent systems indicated below. For mixed solvent systems, the volume ratios are given. Otherwise, parts and percentages are by weight. The following examples are provided to describe the invention in further detail. These examples, which set forth the best mode presently contemplated for carrying out the invention, are intended to illustrate and not to limit the invention. EXAMPLE 1 Preparation of 2,7-dimethyl-8-(2,4-dimethylphenyl)[1,5-a] -pyrazolo-[1,3,5]-triazin-4(3H)-one (Formula 7, where Y is O, R1 is CH3, Z is C-CH3, Ar is 2,4-dimethylphenyl) A. 1-Cyano-1-(2,4-dimethylphenyl)propan-2-one Sodium pellets (9.8g, 0.43 mol) were added portionwise to a solution of 2,4dimethylphenylacetonitrile (48 g, 0.33 mol) in ethyl acetate (150 mL) at ambient temperature. The reaction mixture was heated to reflux temperature and stirred for 16 hours. The resulting suspension was cooled to room temperature and filtered. The collected precipitate was washed with copious amounts of ether and then air-dried. The solid was dissolved in water and a 1N HCl solution was added until the pH = 5-6. The mixture was extracted with ethyl acetate (3 X 200 mL); the combined organic layers were dried over MgSO4 and filtered. Solvent was removed in vacuo to afford a white solid (45.7g, 74% yield): NMR (CDC13,300 MHz):; CI-MS: 188 (M + H). B. 5-Amino-4-(2,4-dimethylphenyl)-3-methylpyrazole A mixture of l-cyano-1-(2,4-dimethylphenyl)propan- 2-one (43.8g, 0.23 mol), hydrazine-hydrate (22 mL, 0.46 mol), glacial acetic acid (45 mL, 0.78 mol) and toluene (500 mL) were stirred at reflux temperature for 18 hours in an apparatus fitted with a Dean-Stark trap. The reaction mixture was cooled to ambient temperature and solvent was removed in vacuo. The residue was dissolved in 6N HCl and the resulting solution was extracted with ether three times. A concentrated ammonium hydroxide solution was added to the aqueous layer until pH = 11. The resulting semi-solution was extracted three times with ethyl acetate. The combined organic layers were dried over MgSO4 and filtered. Solvent was removed in vacuo to give a pale brown viscous oil (34.6g, 75% yield): NMR (CDC13,300 MHz): 7.10 (s, lH), 7.05 (d, 2H, J=1), 2.37 (s, 3H), 2.10 (s, 3H); CI-MS: 202 (M + H). C. 5-Acetamidino-4- (2, 4-d.imethylphenyl) -3- methylpyrazole, acetic acid salt Ethyl acetamidate hydrochloride (60g, 0.48 mol) was added quickly to a rapidly stirred mixture of potassium carbonate (69.5g, 0.50 mol), dichloromethane (120 mL) and water (350 mL). The layers were separated and the aqueous layer was extracted with dichloromethane (2 X 120 mL). The combined organic layers were dried over MgSO4 and filtered. Solvent was removed by simple distillation and the pot residue, a clear pale yellow liquid, (35.0 g) was used without further purification. Glacial aetic acid (9.7 mL, 0.17 mol) was added to a stirred mixture of 5-amino-4-(2,4-dimethylphenyl)-3methylpyrazole ( 34g, 0.17 mol), ethyl acetamidate (22g, 0.25 mol) and acetonitrile (500 mL). The resulting reaction mixture was stirred at room temperature for 3 days; at the end of which time, it was concentrated in vacuo to about one-third of its original volume. The resulting suspension was filtered and the collected solid was washed with copious amounts of ether. The white solid was dried in vacuo (31.4g, 615 yield): NMR (DMSO-d6,300 MHz): 7.00 (s, 1H), 6.90 (dd, 2H, J=7, 1), 2.28 (s, 3H), 2.08 (s, 3H), 2.00 (s, 3H), 1.90 (s, 3H), 1.81 (s, 3H); CI-MS: 243 (M + H). D. 2,7-dimethyl-8-(2,4-dimethylphenyl) [1,5-a]- pyrazolo-[1,3,5]-triazin-4(3H)-one Sodium pellets (23g, 1 mol) were added portionwise to ethanol (500 mL) with vigorous stirring. After all the sodium reacted, 5-acetamidino-4-(2,4dimethylphenyl)-3-methylpyrazole, acetic acid salt (31.2g, 0.1 mol) and diethyl carbonate ( 97 mL, 0.8 mol) were added. The resulting reaction mixture was heated to reflux temperature and stirred for 18 hours. The mix was cooled to room temperature and solvent was removed in vacuo. The residue was dissolved in water and a 1N HCl solution was added slpwly until pH = 5-6. The aqueous layer was extracted with ethyl acetate three times; the combined organic layers were dried over MgSO4 and filtered. Solvent was removed in vacuo to give a pale tan solid (26g, 98% yield): NMR (CDCl3,300 MHz): 7.15(s, 1H), 7.09 (s, 2H), 2.45 (s, 3H), 2.39 (s, 3H), 2.30 (s, 3H); Cl-MS: 269 (M + H). EXAMPLE 2 Preparation of 5-methyl-3-(2,4,6-trimethylphenyl)[1,5-a] [1,2,3]-triazolo-[1,3,5]-triazin-7(6H)-one (Formula 7, where Y is O, R1 is CH3, Z is N, Ar is 2,4,6-trimethylphenyl) A. l-Phenylmethyl-4-(2,4, 6-trimethylphenyl)-5- aminotriazole A mixture of 2,416-trimethylbenzyl cyanide (1.0g, 6.3 mmol)1 benzyl azide (0.92g, 6.9 mmol) and potassium t-butoxide (0.78g, 6.9 mmol) in tetrahydrofuran (lOmL) was stirred at ambient temperature for 2.5 days. The resulting suspension was diluted with water and extracted three times with ethyl acetate. The combined organic layers were dried over MgSO4 and filtered. Solvent was removed in vacuo to give a brown oil. Trituration with ether and filtration afforded a yellow solid (1.12g, 61% yield): NMR (CDCl3,300 MHz):7.60-7.30 (m, 5H), 7.30-7.20 (m, 2H), 5.50 (s, 2H), 3.18 (br s, 2H), 2.30 (s, 3H), 2.10 (s, 6H); CI-MS: 293 (M + H). B. 4-(2,4,6-Trimethylphenyl)-5-aminotriazole Sodium (500 mg, 22 mmol) was added with stirring to a mixture of liquid ammonia (30 mL) and 1-phenylmethyl4-(2,4,6-trimethylphenyl)-5-aminotriazole (l.lg, 3.8 mmol). The reaction mixture was stirred until a dark green color persisted. An ammonium chloride solution mL) was added and the mixture was stirred while warming to ambient temperature over 16 hours. The residue was treated with a 1M HCl solution and filtered. The aqueous layer was basified with a concentrated ammonium hydroxide solution (pH = 9) and then extracted with ethyl acetate three times. The combined organic layers were dried over MgSO4 and filtered. Solvent was removed in vacuo to give a yellow solid (520 mg), which was homogeneous by thin layer chromatography (ethyl acetate): NMR (CDC13,300 MHz): 6.97 (s, 2H), 3.68-3.50 (br.s, 2H), 2.32 (s, 3H), 2.10 (s, 6H); CI-MS: 203 (M + H). C. 4-(2,4,6-Trimethylphenyl)-5-acetamidinotriazole, acetic acid salt A mixture of 4-(2,4,6-trimethylphenyl)-5aminotriazole (400 mg, 1.98 mmol), ethyl acetamidate 261 mg, 3 mmol) and glacial acetic acid (0.1 mL, 1.98 mmol) in acetonitrile (6 mL) was stirred at ambient temperature for 4 hours. The resulting suspension was filtered and the collected solid was washed with copious amounts of ether. Drying in vacuo afforded a white solid (490 mg, 82% yield) : NMR (DMSO-d6,300 MHz):7.907.70 (br s, 0.SH), 7.50-7.20 (br. s, 0.5H), 6.90 (s, 2H), 6.90 (s, 2H), 3.50-3.10 (br s, 3H), 2.30-2.20 (br s, 3H), 2.05 (d, 1H, J = 7), 1.96 (s, 6H), 1.87 (s, 6H) CI-MS: 244 (M + H). D. 5-methyl-3-(2,4,6-trimethylphenyl)[1,5-a] [1,2,3]-triazolo-[1,3,5]-triazin-7(4H)-one Sodium (368 mg, 16.2 mmol) was added with stirring to ethanol (10 mL) at room temperature. After the sodium had reacted1 4-(2,4,6-trimethylphenyl > -5- acetamidino-triazole, acetic acid salt (490 mg, 1.6 mmol) and diethyl carbonate (1.6 mL, 13 mmol) were added. The reaction mixture was stirred at reflux temperature for 5 hours1 then cooled to room temperature. The reaction mixture was diluted with water; a 1N HCl solution was added until pH = 5-6 and three extractions with ethyl acetate were performed. The combined organic layers were dried over MgSO4 and filtered. Solvent was removed in vacuo to give a yellow residue. Trituration with ether and filtration afforded a yellow solid (300 mg, 69% yield): NMR (CDCl3,300 MHz): 6.98 (s, 2H), 2.55 (s, 3H), 2.35 (s, 3H), 2.10 (s, 6H); CI-MS: 270 (M + H). EXAMPLE 3 Preparation of 4- (di (carbomethoxy)methyl) - 2,7-dimethyl-8-(2,4-dimethylphenyl)[1,5-a]-pyrazolo 1,3,5-triazine (Formula 1, where R3 is CH(CHCO2CH3)2, R1 is CH3, Z is C CH3, Ar is 2,4-dimethylphenyl) A. 4-chloro-2,7-dimethyl-8-(2,4-dichlorophenyl) [1,5- a]- pyrazolotriazine A mixture of 2,7-dimethyl-8-(2,4dimethylphenyl) [1,5-a] -pyrazolo-l,315-triazin-4-one (Example 1, 1.38g, 4.5 mmol)1 N,N-dimethylaniline (l mL, 8 mmol) and phosphorus oxychloride (10 mL) was stirred at reflux temperature for 48 hours. The excess phosphorus oxychloride was removed in vacuo. The residue was poured onto icewater, stirred briefly and extracted quickly with ethyl acetate three times. The combined organic layers were washed with ice water, then dried over MgSO4 and filtered. Solvent was removed in vacuo to give a brown oil. Flash column chromatography (ethyl acetate:hexanes::1:4) gave one fraction (Rf = 0.5) Solvent was removed in vacuo to afford a yellow oil (l.Og, 689 yield): NMR (CDCl3,300 MHz): 7.55 (d, lH, J = 1), 7.38 (dd, 1H, J = 7,1 ), 7.30 (d, 1H, J = 7), 2.68 (s, 3H), 2.45 (ss 3H); CI-MS: 327 (M + H). B. 4-(di(carbomethoxy)methyl)-2,7-dimethyl-8-(2,4- dimethylphenyl) [l,5-a]-pyrazolo-l,3,5-triazine Sodium hydride (609 in oil, 80 mg, 2 mmol) was washed with hexanes twice, decanted after each washing and taken up in anhydrous tetrahydrofuran (THF, 1 mL). A solution of diethyl malonate (0.32g, 2 mmol) in THF (2 mL) was added dropwise over 5 min, during which time vigorous gas evolution ensued. A solution of 4-chloro 2,7-dimethyl-8-(2,4-dichlorophenyl) [1,5-a- pyrazolotriazine (0.5g, 1.75 mmol) in THF (2 mL) was added and the reaction mixture was then stirred under a nitrogen atmosphere for 48 hours. The resulting suspension was poured onto water and extracted three times with ethyl acetate. The combined organic layers were washed once with brine, dried over MgSO4 and filtered. Solvent was removed in vacuo to give a brown oil. Column chromatography (ethyl acetate:hexanes::l:9) afforded1 after removal of solvent in vacuo, a pale yellow solid (Rf = 0.2, 250 mg, 35% yield): mp 50-52 C; NMR (CDCl3, 300 MHz): 12.35 (br.s, 1H, 7.15-7.00 (m, 3H), 4.40 (q, 2H, J = 7), 4.30 (q, 2H, J = 7), 2.4, 2.35, 2.3, 2.2, 2.1 (5 s, 12H), 1.4 (t, 3H, J = 1.35-1.25 (m, 3H); CI-HRMS: Calcd: 411.2032, Found: 411.2023. EXAMPLE 6 Preparation of 4-(1,3-dimethoxy-2-propylamino) 2,7-dimethyl-8-(2,4-dichlorophenyl)[1,5-a]-pyrazolo 1,3,5-triazine (Formula 1, where R3 is NHCH(CH2OCH3)2, R1 is CH3, Z is C-CH3, Ar is 2,4-dichlorophenyl) A. 4-chloro-2,7-dimethyl-8-(2,4-dichlorophenyl)[1,5a]- pyrazolotriazine A mixture of 2,7-dimethyl-8-(2,4 dimethylphenyl)[1,5-a]-pyrazolo-1,3,5-triazin-4-one (Example 1, 1.38g, 4.5 mmol), N,N-dimethylaniline (1 mL, 8 mmol) and phosphorus oxychloride (10 mL) was stirred at reflux temperature for 48 hours. The excess phosphorus oxychloride was removed in vacuo. The residue was poured onto ice-water, stirred briefly and extracted quickly with ethyl acetate three times. The combined organic layers were washed with ice water, then dried over MgSO4 and filtered. Solvent was removed in vacuo to give a brown oil. Flash column chromatography (ethyl acetate:hexanes::l:4) gave one fraction (Rf = 0.5) Solvent was removed in vacuo to afford a yellow oil (1.0g, 68% yield): NMR (CDCl3,300 MHz): 7.55 (d, 1H, J = 1), 7.38 (dd, lH, J = 7,1 ), 7.30 (d, 1H, J = 7), 2.68 (s, 3H), 2.45 (s, 3H); CI-MS: 327 (M + H). B. 4- (11 3-dimethoxy-2-propylamino) -2, 7-dimethyl-8- (2,4- dichlorophenyl)[1,5-a]-pyrazolo-1,3,5-triazine A mixture of 4-chloro-2,7-dimethyl-8-(2,4dichlorophenyl)[1,5-a]-pyrazolo-1,3,5-triazine (Part A, 570 mg, 1.74 mmol), 1,3-dimethoxypropyl-2-aminopropane (25mg, 2.08 mmol) and ethanol (10 mL) was stirred at ambient temperature for 18 hours. The reaction mixture was poured onto water (25 mL) and extracted three times with ethyl acetate. The combined organic layers were dried over MgSO4 and filtered. Solvent was removed in vacuo. Column chromatography (CH2Cl2:CH3OH: :50:1) afforded one fraction. Removal of solvent in vacuo gave a solid (250 mg, 35 yield): mp 118-1200C; NMR (CDC13,300 MHz): 7.50 (s, 1H), 7.28 (dd, 2H, J = 8,1), 6.75 (d, 1H, J = 8), 4.70-4.58 (m, 1H), 3.70-3.55 (m, 4H), 3.43 (s, 6H), 2.50 (s, 3H), 2.35 (s, 3H); CI-HRMS: Calcd: 409.1072, Found: 409.1085; Analysis Calcd. for C18H21Cl2N5O2: C, 52.69, K, 5.17, N, 17.07, Cl, 17.28; Found: C, 52.82, H, 5.06, N, 16.77, Cl, 17.50. Using the above procedures and modifications known to one skilled in the art of organic synthesis, the following additional examples of Tables 1-4 may be prepared. The examples delineated in TABLE 1 may be prepared by the methods outlined in Examples 1, 2, 3 or 6. Commonly used abbreviations are: Ph is phenyl, Pr is propyl, Me is methyl, Et is ethyl, Bu is butyl, Ex is Example. TABLE I EMI109.1 Ex. Z R3 Ar mp( C) 6a C-Me NHCH(CH2OMe)2 2,4-C12-Ph 118-120 7b C-Me NHCHPr2 2,4-C12-Ph 114-116 8c C-Me NEtBu 2,4-C12-Ph oil 9d C-Me NPr(CH2-c-C3H5) 2,4-C12-Ph oil 10e C-Me N(CH2CH2OMe12 2,4-C12-Ph oil 11f C-Me NH-3-heptyl 2,4-C12-Ph 90-92 12g C-Me NHCH(Et)*CH2OMe 2,4-C12-Ph 179-181 13h C-Me NEt2 2,4-C12-Ph 133-134 14i C-Me NHCH(CH2OEt)2 2,4-Cl2-Ph oil 15j C-Me NH-3-pentyl 2,4-C12-Ph 139-140 16k C-Me NMePh 2,4-Cl2-Ph 60-62 171 C-Me NPr2 2,4-Cl2-Ph oil 18m C-Me NH-3-hexyl 2,4-Cl2-Ph 130-132 19 C-Me morpholino 2,4-Cl2-Ph 20 C-Me N(CH2Ph)CH2CH2OMe 2,4-Cl2-Ph 21 C-Me NHCH(CH2Ph)CH2OMe 2, 4-Cl2-Ph 22 C-Me NH-4-tetrahydropyranyl 2,4-C12-Ph 23 C-Me NH-cyclopentyl 2,4-Cl2-Ph 24 C-Me 1,2,3,4-tetrahydro- 2,4-Cl2-Ph isoquinolinyl 25 C-Me CH2-(1,2,3,4-tetrahydro- 2,4-C12-Ph isoquinolinyl) 26n C-Me OEt 2,4-C12-Ph 141-143 27 C-Me OCH(Et)CH2OMe 2,4-Cl2-Ph 28 C-Me OCH2Ph 2,4-C12-Ph 29 C-Me 0-3-pentyl 2,4-C12-Ph 30 C-Me SEt 2,4-C12-Ph 31 C-Me S(O)Et 2,4-C12-Ph 32 C-Me SO2Et 2,4-C12-Ph 33 C-Me CH(CO2Et)2 2,4-C12-Ph 34 C-Me C(Et) (CO2Et)2 2,4-Cl2-Ph 35 C-Me CH(Et)CH2OH 2,4-C12-Ph 36 C-Me CH(Et)CH2OMe 2,4-C12-Ph 37 C-Me CONMe2 2,4-C12-Ph 38 C-Me COCH3 2,4-Cl2-Ph 39 C-Me CH(OH)CH3 2,4-Cl2-Ph 40 C-Me C(OH)Ph-3-pyridyl 2,4-Cl2-Ph 41 C-Me Ph 2, 4-Cl2-Ph 42 C-Me 2-CF3-Ph 2,4-Cl2-Ph 43 C-Me 2-Ph-Ph 2,4-Cl2-Ph 44 C-Me 3-pentyl 2,4-C12-Ph 45 C-Me cyclobutyl 2,4-Cl2-Ph 46 C-Me 3-pyridyl 2,4-Cl2-Ph 47 C-Me CH(Et)CH2CONMe2 2,4-Cl2-Ph 48 C-Me CH(Et)CH2CH2NMe2 2,4-Cl2-Ph 490 C-Me NHCH(CH2OMe)2 2,4,6-Me3-Ph 125-127 50 C-Me NHCHPr2 2,4,6-Me3-Ph 51 C-Me NEtBu 2,4,6-Me3-Ph 52 C-Me NPr(CH2-c-C3Hs) 2,4,6-Me3-Ph 53ae C-Me N(CH2CH2OMe)2 2,4,6-Me3-Ph 123-124 54 C-Me NH-3-heptyl 2,4,6-Me3-Ph 55ac C-Me NHCH(Et)CH2OMe 2,4,6-Me3-Ph 145-146 56ah C-Me NEt2 2,4,6-Me3-Ph 88-90 57ai C-Me NHCH(CH2OEt)2 2,4,6-Me3-Ph 132-134 58ad C-Me NH-3-pentyl 2,4,6-Me3-Ph 134-135 59 C-Me NMePh 2,4,6-Me3-Ph 60 C-Me NPr2 2,4,6-Me3-Ph 61 C-Me NH-3-hexyl 2,4,6-Me3-Ph 62 C-Me morpholino 2,4,6-Me3-Ph 63 C-Me N(CH2Ph)CH2CH2OMe 2,4,6-Me3-Ph 64 C-Me NHcH(cH2ph)cH2oMe 2,4, 6-Me3-Ph 65 C-Me NH-4-tetrahydropyranyl 2,4,6-Me3-Ph 66 C-Me NH-cyclopentyl 2,4,6-Me3-Ph 67 C-Me 1,2,3,4-tetrahydro- 2,4,6-Me3-Ph isoquinolinyl 68 C-Me CH2-(1,2,3,4-tetrahydro- 2,4,6-Me3-Ph isoquinolinyl) 69 C-Me OEt 2,4,6-Me3-Ph 70 C-Me OCH(Et)CH20Me 2,4,6-Me3-Ph 71 C-Me OCH2Ph 2,4,6-Me3-Ph 72 C-Me 0-3-pentyl 2,4,6-Me3-Ph 73 C-Me SEt 2,4,6-Me3-Ph 74 C-Me S(O)Et 2,4,6-Me3-Ph 75 C-Me S02Et 2,4,6-Me3-Ph 76 C-Me CH(C02Et)2 2,4,6-Me3-Ph 77 C-Me C(Et)(C02Et)2 2,4,6-Me3-Ph 78 C-Me CH(Et)CH20H 2,4,6-Me3-Ph 79 C-Me CH(Et)GH20Me 2,4,6-Me3-Ph 80 C-Me CONMe2 2,4,6-Me3-Ph 81 C-Me COCH3 2,4,6-Me3-Ph 82 C-Me CH(OH)CH3 2,4,6-Me3-Ph 83 C-Me C(OH)Ph-3-pyridyl 2,4,6-Me3-Ph 84 C-Me Ph 2,4,6-Me3-Ph 85 C-Me 2-CF3-Ph 2,4,6-Me3-Ph 86 C-Me 2-Ph-Ph 2,4,6-Me3-Ph 87 C-Me 3-pentyl 2,4,6-Me3-Ph 88 C-Me cyclobutyl 2,4,6-Me3-Ph 89 C-Me 3-pyridyl 2,4,6-Me3-Ph 90 98v C-Me NHCH(Me) CH20Me 2,4-Me2-Ph 102-104 99w C-Me OCH(Et)CH20Me 2,4-Me2-Ph oil 100x C-Me NPr-c-C3H5 2,4-Me2-Ph oil 101Y C-Me NHCH(Me)CH2NMe2 2,4-Me2-Ph 47-48 102z C-Me N(c-C3H5)CH2CH2CN 2,4-Me2-Ph 117-118 103aa C-Me N(Pr)CH2CH2CN 2,4-Me2-Ph oil 104ab C-Me N(Bu)CH2CH2CN 2,4-Me2-Ph oil 105 C-Me NHCHPr2 2,4-Me2-Ph 10@ C-Me NEtBu 2,4-Me2-Ph 107 C-Me NPr(CH2-c-C3H5) 2,4-Me2-Ph 108 C-Me NH-3-heptyl 2,4-Me2-Ph 109 C-Me NEt2 2,4-Me2-Ph 110 C-Me NHCH(CH2OEt)2 2,4-Me2-Ph 111 C-Me NH-3-pentyl 2,4-Me2-Ph 112 C-Me NMePh 2,4-Me2-Ph 113 C-Me NPr2 2,4-Me2-Ph 114 C-Me NH-3-hexyl 2,4-Me2-Ph 115 C-Me morpholino 2, 4-Me2-Ph 116 C-Me N(CH2Ph)CH2CH20Me 2,4-Me2-Ph 117 C-Me NHCH(CH2Ph)CH20Me 2,4-Me2-Ph 118 C-Me NH-4-tetrahydropyranyl 2,4-Me2-Ph 119 C-Me NH-cyclopentyl 2,4-Me2-Ph 120 C-Me 1,2,3,4-tetrahydro- 2,4-Me2-Ph isoquinolinyl 121 C-Me CH2-(1,2,3,4-tetrahydro- 2,4-Me2-Ph isoquinolinyl) 122 C-Me OEt 2,4-Me2-Ph 123 C-Me OCH(Et)CH20Me 2,4-Me2-Ph 124 C-Me OCH2Ph 2,4-Me2-Ph 125 C-Me 0-3-pentyl 2,4-Me2-Ph 126 C-Me SEt 2,4-Me2-Ph 127 C-Me S(O)Et 2,4-Me2-Ph 128 C-Me S02Et 2,4-Me2-Ph 3 C-Me CH(C02Et)2 2,4-Me2-Ph 50-52 129 C-Me C(Et)(C02Et)2 2,4-Me2-Ph 130 C-Me CH(Et)CH2OH 2,4-Me2-Ph 131 C-Me CH(Et)CH2OMe 2,4-Me2-Ph 132 C-Me CH(Et)CH2OEt 2,4-Me2-Ph 133 C-Me CONMe2 2,4-Me2-Ph 134 C-Me COCH3 2,4-Me2-Ph 135 C-Me CH(OH)CH3 2,4-Me2-Ph 136 C-Me C(OH)Ph-3-pyridyl 2,4-Me2-Ph 137 C-Me Ph 2, 4-Me2-Ph 138- C-Me 2-CF3-Ph 2,4-Me2-Ph 139 C-Me 2-Ph-Ph 2,4-Me2-Ph 140 C-Me 3-pentyl 2,4-Me2-Ph 141 C-Me cyclobutyl 2,4-Me2-Ph 142 C-Me 3-pyridyl 2,4-Me2-Ph 143 C-Me CH(Et)cH2CONMe2 2,4-Me2-Ph 144 C-Me CH(Et)CH2CH2NMe2 2,4-Me2-Ph 145bc C-Me NHCH(CH2OMe)2 2-Me-4-MeO-Ph 45-46 146bd C-Me N(CH2CH2OMe)2 2-Me-4-MeO-Ph oil 147be C-Me NHCH(Et)CH2OMe 2-Me-4-MeO-Ph 86-88 148bf C-Me N(Pr)CH2CH2CN 2-Me-4-MeO-Ph oil 149 C-Me OCH(Et)CH2OMe 2-Me-4-MeO-Ph 150af C-Me NHCH(CH2OMe)2 2-Br-4-MeO-Ph 88-90 151al C-Me N(CH2CH2OMe)2 2-Br-4-MeO-Ph oil 152ag C-Me NHCH(Et)CH2OMe 2-Br-4-MeO-Ph 95-97 153 C-Me N(Pr)CH2CH2CN 2-Br-4-MeO-Ph 154 C-Me OCH(Et) CH2OMe 2-Br-4-MeO-Ph 155 C-Me NHCH(CH2oMe)2 2-Me-4-NMe2-Ph 156 C-Me N(CH2CH20Me)2 2-Me-4-NMe2-Ph oil 157 C-Me NHCH(Et)CH2OMe 2-Me-4-NMe2-Ph 158 C-Me N(Pr)CH2CH2CN 2-Me-4-NMe2-Ph 159 C-Me OCH(Et)CH2OMe 2-Me-4-NMe2-Ph 160 C-Me NHCH(CH2OMe)2 2-Br-4-NMe2-Ph 161 C-Me N(CH2cH2OMe)2 2-Br-4-NMe2-Ph 162 C-Me NHCH(Et)CH2OMe 2-Br-4-NMe2-Ph 163 C-Me N(Pr)CH2CH2CN 2-Sr-4-NMe2-Ph 164 C-Me OCH(Et)cH2OMe 2-Br-4-NMe2-Ph 165 C-Me NHCH(CH2OMe)2 2-Br-4-i-Pr-Ph 166 C-Me N(CH2CH2OMe)2 2-Br-4-i-Pr-Ph 167 C-Me NHCH(Et)CH2OMe 2-Br-4-i-Pr-Ph 168 C-Me N(Pr)CH2CH2CN 2-Br-4-i-Pr-Ph 169 C-Me OCH(Et)CH2OMe 2-Br-4-i-Pr-Ph 170 C-Me NHCH(CH2OMe) 2 2-Br-4-Me-Ph 171 C-Me N(CH2CH2OMe)2 2-Br-4-Me-Ph 172 C-Me NHCH(Et)CH2OMe 2-Br-4-Me-Ph 173 C-Me N(Pr)CH2CH2CN 2-Br-4-Me-Ph 17x C-Me OCH(Et)CH2OMe 2-Br-4-Me-Ph 175ar C-Me NHCH(cH2OMe)2 2-Me-4-Br-Ph 108-109 176 C-Me N(CH2CH20Me)2 2-Me-4-Br-Ph 177 C-Me NHCH(Et)CH2OMe 2-Me-4-Br-Ph 178 C-Me N(Pr)CH2CH2CN 2-Me-4-Br-Ph 179 C-Me OCH(Et)CH2OMe 2-Me-4-Br-Ph 180 C-Me NHCH(CH2OMe)2 2-C1-4,6-Me2-Ph 181 C-Me N(CH2cH2OMe)2 2-C1-4,6-Me2-Ph 182 C-Me NHCH(CH2OMe)2 4-Br-2,6-(Me)2-Ph 183 C-Me N(CH2CH2OMe)2 4-Br-2,6-(Me)2-Ph 184 C-Me NHCH(CH2OMe)2 4-i-Pr-2-SMe-Ph 185 C-Me N(CH2cH2OMe)2 4-i-Pr-2-SMe-Ph 186 C-Me NHCH(CH2OMe)2 2-Br-4-CF3-Ph 187 C-Me N(CH2CH2OMe)2 2-Br-4-CF3-Ph 188 C-Me NHCH(cH2OMe)2 2-Br-4,6-(MeO) 2-Ph 189 C-Me N(CH2CH2OMe)2 2-8r-4,6-(MeO)2-Ph 190 C-Me NHCH(CH2OMe)2 2-Cl-4,6-(MeO)2-Ph 191 C-Me N(CH2CH2OMe)2 2-Cl-4,6-(MeO)2-Ph 192 C-Me NHCH(CH2OMe)2 2,6-(Me)2-4-SMe-Ph 193 C-Me N(CH2CH2OMe)2 2,6-(Me)2-4-SMe-Ph 194 C-Me NHCH(CH2OMe)2 4-(COMe)-2-Br-Ph 195 C-Me N(CH2OH2OMe)2 4-(COMe)-2-Br-Ph 196 C-Me NHCH(CH2OMe)2 2,4,6-Me3-pyrid-3-yl 197 C-Me N(CH2CH2OMe)2 2,4,6-Me3-pyrid-3-yl 19B C-Me NHCH(CH2OMe)2 2,4-(Br)2-Ph 199 C-Me N(CH2CH2OMe)2 2,4-(Br)2-Ph 200 C-Me NHCH(CH2OMe)2 4-i-Pr-2-SMe-Ph 201 C-Me N(CH2CH2OMe)2 4-i-Pr-2-SMe-Ph 202 C-Me NHCH(CH2OMe)2 4-i-Pr-2-SO2Me-Ph 203 C-Me N(CH2CH2GMe)2 4-i-Pr-2-S02Me-Ph 204 C-Me NHCH(CH2OMe)2 2,6-(Me)2-4-SMe-Ph 205 C-Me N(CH2cH2OMe)2 2,6-(Me) 2-4-SMe-Ph 206 C-Me NHCH(CH20Me)2 2,6-(Me)2-4-S02Me-Ph 207 C-Me N(CH2CH20Me)2 2,6-(Me)2-4-SO2Me-Ph 208 C-Me NHCH(CH2OMe)2 2-I-4-i-Pr-Ph 209 C-Me N(CH2CH2OMe)2 2-I-4-i-Pr-Ph 21@ C-Me NHCH(cH2OMe)2 2-Br-4-N(Me)2-6-MeO-Ph 211 C-Me N(CH2CH2OMe)2 2-Br-4-N(Me)2-6-Me0-Ph 212 C-Me NHCH(CH2OMe)2 2,4-[SMe]2-Ph 213 C-Me N(CH2CH2OMe)2 2,4-[SMe]2-Ph 214 C-Me NHCH(CH2OMe)2 2,4-[SO2Me]2-Ph 215 C-Me NtCH2CH2OMe)2 2,4-[SO2Me]2-Ph 216 C-Me NHCH(CH2OMe)2 4-i-Pr-2-SMe-Ph 217 C-Me N(CH2CH20Me)2 4-i-Pr-2-SMe-Ph 218 0-Me NHCH(cH2OMe)2 4-i-Pr-2-S02Me-Ph 219 C-Me N(CH2CH2OMe)2 4-i-Pr-2-SO2Me-Ph 220 C-Me NHCH(CH2OMe)2 2-N(Me)2-4-Me-Ph 221 C-Me N(CH2CH2OMe)2 2-N(Me)2-4-Me-Ph 222 C-Me NHCH(CH2OMe)2 2-MeS-4,6-(Me)2-Ph 223 C-Me N(CH2CH2OMe)2 2-MeS-4, 6-(Me)2-Ph 224 C-Me NHCH(CH20Me)2 2-(CH3CO)-4,6-(Me)2-Ph 225 C-Me N(CH2CH20Me)2 2-(CH3CO)-4,6-(Me)2-Ph 226 H NHCH(OH2OMe)2 2,4-Me2-Ph 227 H NHCH(CH2OMe)2 2,4-Me2-Ph 228 cE3 N(CH2CH2OMe)2 2,4-Me2-Ph 229 03 N(CH2CH20Me)2 2,4-Me2-Ph 230 N NHcH(cH2oMe)2 2,4,6-Me3-Ph 231 N NHCHPr2 2,4,6-Me3-Ph 232 N NEtBu 2,4,6-Me3-Ph 233 N NPr(CH2-c-C3H5) 2,4,6-Me3-Ph 234 N N(cH2cH2oMe)2 2,4,6-Me3-Ph 235 N NH-3-heptyl 2,4,6-Me3-Ph 236 N NHCH(Et)CH2OMe 2,4,6-Me3-Ph 237 N NEt2 2,4,6-Me3-Ph 238 N NHCH(CH2OEt)2 2,4,6-Me3-Ph 239 N NH-3-pentyl 2,4,6-Me3-Ph 240 N NMePh 2,4,6-Me3-Ph 241 N NPr2 2,4,6-Me3-Ph 242 N NH-3-hexyl 2,4,6-Me3-Ph 243 N morpholino 2,4,6-Me3-Ph 244 N N(CH2Ph)CH2CH2OMe 2,4,6-Me3-Ph 245 N NHCH(CH2Ph)CH2OMe 2,4, 6-Me3-Ph 24' N NH-4-tetrahydropyranyl 2,4,6-Me3-Ph 247 N NH-cyclopentyl 2,4,6-Me3-Ph 248 N 1,2,3,4-tetrahydro- 2,4,6-Me3-Ph isoquinolinyl 249 N CH2-(1,2,3,4-tetrahydro- 2,4,6-Me3-Ph isoquinolinyl) 250 N OEt 2,4,6-Me3-Ph 251 N OCH(Et)CH2OMe 2,4,6-Me3-Ph 252 N OCH2Ph 2,4,6-Me3-Ph 253 N O-3-pentyl 2,4,6-Me3-Ph 254 N SEt 2,4,6-Me3-Ph 255 N S(O)Et 2,4,6-Me3-Ph 256 N SO2Et 2,4,6-Me3-Ph 257 N CH(CO2Et)2 2,4,6-Me3-Ph 258 N C(Et) (CO2Et)2 2,4,6-Me3-Ph 259 N CH(Et)CH2OH 2,4,6-Me3-Ph 260 N CH(Et)CH2OMe 2,4,6-Me3-Ph 261 N CONMe2 2,4,6-Me3-Ph 262 N COCH3 2,4,6-Me3-Ph 263 N CH(OH)CH3 2,4,6-Me3-Ph 264 N C(OH)Ph-3-pyridyl 2,4,6-Me3-Ph 265 N Ph 2,4,6-Me3-Ph 266 N 2-CF3-Ph 2,4,6-Me3-Ph 267 N 2-Ph-Ph 2,4,6-Me3-Ph 268 N 3-pentyl 2,4,6-Me3-Ph 269 N cyclobutyl 2,4,6-Me3-Ph 270 N 3-pyridyl 2,4, 6-Me3-Ph 271 N CH(Et)CH2CONMe2 2,4,6-Me3-Ph 272 N CH(Et)CH2CH2NMe2 2,4,6-Me3-Ph 273 N NHCH(CH2OMe)2 2,4-Me2-Ph 274 N NHCHPr2 2,4-Me2-Ph 275 N NEtBu 2,4-Me2-Ph 276 N NPr(CH2-c-C3H5) 2,4-Me2-Ph 277 N N(CH2cH2OMe)2 2,4-Me2-Ph 278 N NH-3-heptyl 2,4-Me2-Ph 279 N NHCH(Et)CH2OMe 2,4-Me2-Ph 28 N NEt2 2,4-Me2-Ph 281 N NHCH(CH2OEt)2 2,4-Me2-Ph 282 N NH-3-pentyl 2,4,-Me2-Ph 283 N NMePh 2,4,-Me2-Ph 284 N NPr2 2,4-Me2-Ph 285 N NH-3-hexyl 2,4-Me2-Ph 286 N morpholino 2,4-Me2-Ph 287 N N(CH2Ph)CH2CH20Me 2,4-Me2-Ph 288 N NHCH(CH2Ph)CH2OMe 2, 4-Me2-Ph 289 N NH-4-tetrahydropyranyl 2,4-Me2-Ph 290 N NH-cyclopentyl 2,4-Me2-Ph 291 N 1,2,3, 4-tetrahydro- 2,4,-Me2-Ph isoquinolinyl 292 N CH2-(1,2,3,4-tetrahydro- 2, 4-Me2-Ph isoquinolinyl) 293 N OEt 2,4-Me2-Ph 294 N OCH(Et)CH20Me 2,4-Me2-Ph 295 N OCH2Ph 2,4-Me2-Ph 296 N 0-3-pentyl 2,4-Me2-Ph 297 N SEt 2,4-Me2-Ph 298 N S(O)Et 2,4-Me2-Ph 299 N S02Et 2,4-Me2-Ph 300 N CH(CO2Et)2 2,4-Me2-Ph 301 N C(Et) (CO2Et)2 2,4-Me2-Ph 302 N CH(Et)CH2OH 2,4-Me2-Ph 303 N CH(Et)CH20Me 2,4-Me2-Ph 304 N CONMe2 2,4-Me2-Ph 305 N COCH3 2,4-Me2-Ph 306 N CH(OH)CH3 2,4-Me2-Ph 307 N C(OH)Ph-3-pyridyl 2,4-Me2-Ph 308 N Ph 2,4-Me2-Ph 309 N 2-CF3-Ph 2,4-Me2-Ph 310 N 2-Ph-Ph 2,4-Me2-Ph 311 N 3-pentyl 2,4-Me2-Ph 312 N cyclobutyl 2,4-Me2-Ph 313 N 3-pyridyl 2,4-Me2-Ph 31i N CH(Et)CH2CONMe2 2,4-Me2-Ph 315 N CH(Et) CH2CH2NMe2 2, 4-Me2-Pb 316an C-Me NEt2 2-Br-4-MeO-Ph oil 317am C-Me NH-3-pentyl 2-Br-4-MeO-Ph oil 318aj C-Me NHCH(CH2CH2OMe)CH2OMe 2,4,6-Me3-Ph 101-103 319ao C-Me NH(c-C3H5) 2,4-Me2-Ph oil 320ak C-Me morpholino 2,4,6-Me3-Ph 139-141 321ap C-Me NHCH(CH2OMe)2 2-CN-4-Me-Ph 152-153 322aq C-Me N(c-C3H5)CH2CH2CN 2,4,6-Me3-Ph 149-151 324as C-Me NHCH(CH2CH2oMe)CH2OMe 2-Me-4-Br-Ph 115-117 325at C-Me NHCH(cH2OMe)2 2,5-Me2-4-MeO-Ph 55-57 326au C-Me N(CH2CH20Me)2 2,5-Me2-4-MeO-Ph 72 327av C-Me NH-3-pentyl 2,5-Me2-4-MeO-Ph 45-47 328aw C-Me NEt2 2,5-Me2-4-MeO-Ph oil 329aX C-Me NHCH(CH2OMe)2 2-C1-4-MePh 80-81 330ay C-Me NCH(Et)CH2OMe 2-C1-4-MePh 77-79 331az C-Me N(CH2CH2OMe)2 2-C1-4-MePh oil 332ba C-Me (S) -NHCH(CH2CH2OMe)CH2OMe 2-C1-4-MePh 139-140 333bb C-Me N(c-C3H5)CH2CH2CN 2,5-Me2-4-MeOPh 120-122 334bg C-Me NEt2 2-Me-4-MeOPh oil 335bh C-Me OEt 2-Me-4-MeOPh oil 336bi C-Me (S)-NHCH(CH2CH2OMe)CH2OMe 2-Me-4-MeOPh oil 337bj C-Me N(c-C3Hs)CH2CH2CN 2-Me-4-MeOPh 129 338bk C-Me NHCH(CH2CH20Et)2 2-Me-4-MeOPh amorph. 339 C-Me N(c-C3H5)CH2CH2CN 2,4-C12-Ph 109-110 340 C-Me (S)@NHCH(CH2CH2OMe)CH2OMe 2,4-C12-Ph 93-94 341 C-Me NH-3-pentyl 2-Me-4-BrPh 118-119 342 C-Me N(CH2CH2OMe)2 2-Me-4-BrPh oil 343 C-Me NHCH(CH2-iPr)CH2OMe 2,4-Me2-Pb oil 344 C-Me NHCH(Pr)CH2OMe 2,4-Me2-Ph 94-95 345 C-Me NHCH(Et)CH2OEt 2,4-Me2-Ph 346 C-Me NHCH(CH2OMeXCH2CH2OMe 2-Me-4-Me2NPh oil 347 C-Me NEt2 2-Me-4-ClPh oil 348 C-Me NH-3-pentyl 2-Me-4-ClPh 122-124 349 C-Me N(CH2CH20Me)2 2-Me-4-ClPh oil 350 C-Me NHCH(CH2OMe)2 2-Me-4-ClPh 122-123 351 C-Me NEt2 2-Me-4-clPh oil 352 C-Me NEt2 2-C1-4-MePh oil 353 C-Me NH-3-pentyl 2-C1-4-MePh 120-121 354 C-Me NHCH(CH2OMe) 2 2-C1-4-MeOPh 355bl C-Me N(CH2CH2OMe)2 2-C1-4-MeOPh oil 356bm C-Me NHCH(Et)CH2OMe 2-Cl-4-MeOPh 108-110 357bn C-Me N(c-Pr)CH2CH2CN 2-C1-4-MeOPh 127-129 358bo C-Me NEt2 2-C1-4-MeOPh oil 359bp C-Me NH-3-pentyl 2-C1-4-MeOPh 77-79 360 C-Me NHCH(Et)CH2CH2OMe 2-C1-4-MeOPh 361 C-Me NHCH(Me)CH2CH2OMe 2-Cl-4-MeOPh 362 C-Me NHCH(Et)CH2CH2OMe 2-Br-4-MeOPh 363 C-Me NHCH(Me)CH2CH2OMe 2-Br-4-MeOPh 364 C-Me NHCH(Et)0H20H20Me 2-Me-4-MeOPh 365 C-Me NHCH(Me)CH2CH20Me 2-Me-4-MeOPh 366 C-Me NHCH(cH2OMe)2 2-Cl-4,5-(MeO)2Ph 367 C-Me N(CH2CH2OMe)2 2-Cl-4,5-(MeO)2Ph 368 C-Me NHCH(Et)CH2OMe 2-Cl-4,5-(MeO)2Ph 369 C-Me N(c-Pr)CH2CH2CN 2-Cl-4,5-(MeO)2Ph 370 C-Me NEt2 2-Cl-4,5-(MeO) 2Ph 371 C-Me NH-3-pentyl 2-C1-4,5-(Me0)2Ph 372 C-Me NHCH(Et)CH2CH2OMe 2-C1-4,5-(MeO)2Ph 373 C-Me NHCH(Me)CH2CH20Me 2-Cl-4,5-(MeO)2Ph 374bq C-Me NHCH(CH2OMe)2 2-Br-4,5-(MeO)2Ph 137-138 375 C-Me N(CH2cH2OMe)2 2-Br-4,5-(MeO)2Ph 376br C-Me NHCH(Et)CH2OMe 2-Br-4,5-(MeO)2Ph 147-148 377 C-Me N(c-Pr)CH2CH2CN 2-Br-4,5-(Me0)2Ph 378bs C-Me NEt2 2-Br-4,5-(Me0)2Ph 52-58 379 C-Me NH-3-pentyl 2-Br-4,5-(MeO)2Pb 380 C-Me NHCH(Et)CH2CH20Me 2-Br-4,5-(MeO)2Ph 381 C-Me NHCH(Me)CH2CH2oMe 2-Br-4,5-(MeO)2Ph 382 C-Me NHCH(CH2OMe)2 2-Cl-4,6-(MeO)2Ph 383 C-Me N(CH2CH2OMe)2 2-Cl-4,6-(MeO)2Ph 384 C-Me NHCH(Et)CH2OMe 2-Cl-4,6-(MeO)2Ph 385 C-Me N(c-Pr)CH2CH2CN 2-Cl-4,6-(MeO) 2Ph 386 C-Me NEt2 2-Cl-4,6-(MeO)2Ph 381 C-Me NH-3-pentyl 2-C1-4,6-(MeO)2Ph 388 C-Me NHCH(Et)CH2CH2OMe 2-Cl-4,6-(MeO)2Ph 389 C-Me NHCH(Me)CH2CH20Me 2-Cl-4,6-(MeO)2Ph 390 C-Me NHCH(cH2OMe)2 2-Me-4,6-(MeO)2Ph 391 C-Me N(CH2CH20Me)2 2-Me-4,6-(MeO)2Ph 392 C-Me NHCH(Et)CH20Me 2-Me-4,6-(MeO)2Ph 393 C-Me N(c-Pr)CH2CH2CN 2-Me-4,6-(MeO)2Ph 395 C-Me NEt2 2-Me-4,6-(MeO)2Ph 396 C-Me NH-3-pentyl 2-Me-4,6-(MeO)2Ph 397 C-Me NHCH(Et)CH2CH2OMe 2-Me-4,6-(MeO)2Ph 398 C-Me NHCH(Me)cH2cH2oMe 2-Me-4,6-(Me0)2Ph 399 C-Me N(c-Pr)CH2CH2CN 2-Br-4,6-(MeO)2Ph 400 C-Me NEt2 2-Br-4,6-(MeO)2Ph 401 C-Me NH-3-pentyl 2-Br-4,6-(Me0)2Ph 402 C-Me NHCH(Et)CH2CH20Me 2-Br-4,6-(MeO)2Ph 403 C-Me NHCH(Me)CH2CH20Me 2-Br-4,6-(Me0) 2Ph 404 C-Me NHCH(Et)CH2CH20Me 2-Me-4-MeOPh 405 C-Me NHCH(Me)CH2CH2OMe 2-Me-4-MeOPh 406 C-Me NHCH(CH20Me)2 2-MeO-4-MePh 407 C-Me N(CH2CH2OMe)2 2-MeO-4 -MePh 408 C-Me NHCH(Et)CH2OMe 2-MeO-4-MePh 409 C-Me N(c-Pr)CH2CH2CN 2-MeO-4-MePh 410 C-Me NEt2 2-MeO-4-MePh 411 C-Me NH-3-pentyl 2-Me0-4-MePh 412 C-Me NHCH(Et)CH2CH2OMe 2-MeO-4-MePh 413 C-Me NHCH(Me)CH2CH2OMe 2-MeO-4-MePh 414 C-Me NHCH(CH2OMe)2 2-MeO-4-MePh 415 C-Me N(CH2cH2OMe)2 2-Me0-4-MePh 416 C-Me NHCH(Et)CH2OMe 2-MeO-4-MePh 417 C-Me N(c-Pr)CH2CH2CN 2-MeO-4-MePh 418 C-Me NEt2 2-MeO-4-MePh 419 C-Me NH-3-pentyl 2-MeO-4-MePh 420 C-Me NHCH(Et)CH2CH20Me 2-MeO-4-MePh 421 C-Me NHCH(Me)CH2CH20Me 2-MeO-4-MePh 423bt C-Me NHCH(cH2OMe) 2 2-Me3-4-clph oil 424 C-Me N(CH2CH20Me)2 2-MeO-4-ClPh 425 C-Me NHCH(Et)CH2OMe 2-MeO-4-ClPh 426 C-Me N(c-Pr)CH2CH2CN 2-MeO-4-ClPh 427 C-Me NEt2 2-MeO-4-ClPh 428 C-Me NH-3-pentyl 2-MeO-4-ClPh 429 C-Me NHCH(Et)CH2CH2OMe 2-MeO-4-ClPh 430 C-Me NHCH(Me)CH2CH20Me 2-MeO-4-ClPh NOTES FOR TABLE 1: a) Analysis Calcd: C, 52.69, H, 5.17, N, 17.07, Cl, 17.28; Found: C, 52.82, H, 5.06, N, 16.77, Cl, 17.50. b) CI-HRMS: Calcd: 406.1565, Found: 405.1573 (M + H); Analysis Calcd: C: 59.11; H: 6.20; N: 17.23; Cl: 17.45; Found: C: 59.93; H: 6.34; N: 16.50; Cl: 16.95; NMR (CDCl3, 300 MHz): 0.95 (t, J = 8, 4H), 1.30 1.40 (m, 4H), 1.50-1.75 (m, 4H), 2.35 (s, 3H), 2.48 (s, 3H), 4.30-4.45 (m, 1H), 6.15 (d, J = 8, 1H), 7.30 (s, 2H), 7.50 (s, 1H) c) CI-HRMS: Calcd: 392.1409, Found: 392.1388 (M + H); NMR (CDCl3, 300 MHz): 1.00 (t, J =8, 3H), 1.35 (t, J = 8, 3H), 1.41 (q, J = 8, 2H), 1.65-1.85 (m, 2H), 2.30 (s, 3H), 2.40 (s, 3H), 3.85-4.20 (m, 4H), 7.30 (s, 2H), 7.50 (s, lH). d) CI-HRMS: Calcd: 404.1409, Found: 404.1408 (M + H); NMR(CDCl3, 300 MHz): 0.35-0.45 (m, 2H), 0.52-0.62 (m, 2H), 0.98 (t, J = 8, 3H), 1.70-1.90 (m, 2H), 2.30 (s, 3H), 2.40 (S, 3H), 3.85-4.02 (m, 2H), 4.02-4.20 (m, 2H), 7.30 (s, 2H), 7.50 (s, 1H) e) CI-HRMS: Calcd: 424.1307, Found: 424.1307 (M + H): NMR (CDCl3, 300 MHz): 2.28 (s, 3H), 2.40 (s, 3H), 3.40 (s, 6H), 3.75 (t, J = 8, 4H), 4.20-4.45 (m, 4H), 7.30 (s, 2H), 7.50 (s, 1H). f) CI-HRMS: Calcd: 406.1565, Found: 406.1578 (M + H); NMR (CDCl3, 300 MHz): 0.90 (t, J = 8, 3H), 1.00 (t, J = 8, 3H), 1.28-1.45 (m, 4H), 1.50-1.80 (m, 4H), 2.35 (s, 3H), 2.50 (s, 3H), 4.20-4.35 (m, 1H), 6.10-6.23 (m, 1H) , 7.30 (s, 2H), 7.50 (s, 1H) g) CI-HRMS: Calcd: 394.1201, Found: 394.1209 (M + H); NMR (CDCl3, 300 MHz): 1.02 (t, J = 8, 3H), 1.65 1.90 (m, 2H), 2.35 (s, 3H), 2.48 (s, 3H), 3.40 (s, 3H), 3.50-3.60 (m, 2H), 4.35-4.45 (brs, 1H), 6.50 6.60 (m, 1H), 7.30 (s, 2H), 7.50 (s, 1H) h) CI-HRMS: Calcd: 364.1096, Found: 364.1093 (M + H); Analysis: Calcd: C: 56.05; H: 5.27; N: 19.23; Cl: 19.46; Found: C: 55.96; H: 5.24; N: 18.93; Cl: 19.25; NMR (CDCl3, 300 MHz): 1.35 (t, J = 8, 6H), 2.30 (3, 3H) , 2.40 (s, 3H), 3.95-4.15 (m, 4H), 7.30 (s, 2H), 7.50 (d, J = 1, 1H). i) CI-HRMS: Calcd: 438.1464, Found: 438.1454 (M + H); NMR (CDCl3, 300 MHz): 1.22 (t, J = 8, 6H), 2.35 (s, 3H), 2.47 (s, 3H), 3.39 (q, J = 8, 4H), 3.65 (dd, J = 8, 1, 2H), 3.73 (dd, J = 8, 1, 2H), 4.55-4.65 (m, 1H), 6.75 (d, J = 8, 1H), 7.30 (d, J = 1, 2H), 7.50 (S, 1H) j) CI-HRMS: Calcd: 378.1252, Found: 378.1249 (M + H); Analysis: Calcd: C: 57.15; H: 5.61; N: 18.51; Cl: 18.74; Found: C: 57.56; H: 5.65; N: 18.35; Cl: 18.45; NMR (CDCl3, 300 MHz): 1.00 (t, J = 8, 6H), 1.55 1.70 (m, 2H), 1.70-1.85 (m, 2H), 2.35 (s, 3H), 2.50 (s, 3H), 4.15-4.25 (m, 1H), 6.18 (d, J = 8, 1H), 7.30 (s, 2H), 7.50 (s, 1H). k) CI-HRMS: Calcd: 398.0939, Found: 398.0922 (M + H); Analysis: Calcd: C: 60.31; H: 4.30; N: 17.58; Cl: 17.80; Found: C: 60.29; H: 4.59; N: 17.09; Cl: 17.57; NMR (CDCl3, 300 MHz): 2.05 (s, 3H), 2.50 (s, 3H), 3.78 (s, 3H), 7.20-7.45 (m, 7H), 7.50 (d, J = 1, 1H). 1) CI-HRMS: Calcd: 392.1409, Found: 392.1391 (M + H); NMR (CDCl3, 300 MHz): 0.98 (t, J = 8, 6H), 1.70 1.85 (m, 4H), 2.30 (5, 3H), 2.40 (s, 3H), 3.80-4.10 (m, 4H) , 7.30 (s, 2H), 7.50 (d, J = 1, 1H). m) CI-HRMS: Calcd: 392.1409, Found: 392.1415 (M + H); Analysis: Calcd: C: 58.17; H: 5.92; N: 17.85; Cl: 18.07; Found: C: 58.41; H: 5.85: N: 18.10; Cl: 17.75; NMR (CDCl3, 300 MHz): 0.90-1.05 (m, 6H), 1.35-1.55 (m, 2H), 1.55-1.85 (m, 4H), 2.35 (s, 3H), 2.48 (s, 3H), 4.20-4.35 (m, 1H), 6.15 (d, J = 8, 1H), 7.30 (s, 2H), 7.50 (d, J = 1, 1H). n) CI-HRMS: Calcd: 337.0623, Found: 337.0689 (M + H); Analysis: Calcd: C: 53.43; H: 4.18; N: 16.62; Cl: 21.03, Found: C: 53.56; H: 4.33; N: 16.56; Cl: 20.75; NMR (CDCl3, 300 MHz): 1.60 (t, J = 8, 3H), 2.40 (s, 3H), 2.55 (s, 3H), 4.80 (q, J = 8, 2H), 7.30 (d, J = 8, 1H), 7.35 (dd, J = 8, 1, 1H), 7.55 (d, J = 1, lH) o) CI-HRMS: Calcd: 383.2321, Found: 383.2309 (M + H); NMR (CDCl3, 300 MHz): 2.00 (s, 6H), 2.20 (s, 3H), 2.30 (s, 3H), 2.45 (s, 3H), 3.45 (s, 6H), 3.61 (dd, J = 8, 8, 2H), 3.70 (dd, J = 8, 8, 2H), 4.60-4.70 (m, 1H), 6.70 (d, J = 8, 1H), 6.94 (s, 2H). p) CI-HRMS: Calcd: 370.2243, Found: 370.2246 (M + H); Analysis: Calcd: C: 65.02; H: 7.38; N: 18.96; Found: C: 65.22; H: 7.39; N: 18.71; NMR (CDC13, 300 MHz): : 2.18 (s, 3H), 2.30 (s, 3H), 2.45 (s, 3H), 3.45 (s, 6H), 3.60 (dd, J = 8, 8, 2H), 3.69 (dd, J = 8, 8, 2H), 4.60-4.70 (m, 1H), 6.70 (d, J = 8, 1H), 7.05 (d, J = 8, 1H), 7.07 (d, J = 8, 1H), 7.10 (s, 1H). q) CI-HRMS: Calcd: 384.2400, Found: 384.2393 (M + H); NMR (CDC13, 300 MHz): 2.16 (s, 3H), 2.25 (s, 3H), 2.35 (s, 3H), 2.39 (s, 3H), 3.40 (s, 6H), 3.77 (t, J = 8, 4H), 4.20-4.45 (m, 4H), 7.02 (d, J = 8, 1H) 7.05 (s, 1H), 7.10 (d, J = 7, 1H). r) CI-HRMS: Calcd: 354.2294, Found: 354.2271 (M + H); Analysis: Calcd: C: 67.96; H: 7.71; N: 19.81; Found: C: 67.56; H: 7.37; N: 19.60; NMR (CDCl3, 300 MHz): 1.03 (t, J = 8, 3H), 1.65 1.88 (m, 2H), 2.17 (s, 3H), 2.30 (s, 3H), 2.35 (s, 3H), 2.45 (s, 3H), 3.40 (s, 3H), 3.50-3.62 (m, 2H), 4.30-4.45 (m, 1H), 6.51 (d, J = 8, 1H), 7.04 (d, J = 8, 1H), 7.10 (d, J =8, 1H), 7.12 (s, 1H). s) CI-HRMS: Calcd: 338.2345, Found: 338.2332 (M + H); Analysis: Calcd: C: 71.18; H: 8.06; N: 20.75; Found: C: 71.43; H: 7.80; N: 20.70; NMR (CDCl3, 300 MHz): 1.00 (t, J = 8, 6H), 1.55 1.70 (m, 2H), 1.70-1.85 (m, 2H), 2.19 (s, 3H), 2.30 (s, 3H), 2.35 (s, 3H), 2.46 (s, 3H), 4.15-4.26 (m, 1H), 6.17 (d, J = 8, 1H) , 7.06 (d, J = 8, 1H), 7.10 (d, J = 1, 1H) , 7.13 (s, 1H) t) CI-HRMS: Calcd: 324.2188, Found: 324.2188 (M + H); NMR (CDCl3, 300 MHz): 1.25 (t, J = 8, 6H), 2.16 (s, 3H), 2.28 (s, 3H), 2.35 (s, 3H), 2.40 (s, 3H), 3.95-4.20 (m, 4H), 7.05 (dd, J = 8, 1, 1H), 7.07 (s, 1H), 7.10 (d, J = 1, 1H), u) CI-HRMS: Calcd: 346.1780, Found: 346.1785 (M + H); Analysis: Calcd: C: 66.07; H: 5.54; N: 28.39; Found: C: 66.07; H: 5.60; N: 27.81; NMR (CDC13, 300 MHz): 2.15 (s, 3H), 2.32 (s, 3H) 2.17 (s, 3H), 2.52 (s, 3H), 5.25-5.35 (m, 4H), 7.08 (s, 2H), 7.15 (s, 1H). v) CI-HRMS: Calcd: 340.2137, Found: 340.2137 (M + H); Analysis: Calcd: C: 67.23; H: 7.42; N: 20.63; Found:C: 67.11; H: 7.39; N: 20.26; NMR (CDCl3, 300 MHz): 1.40 (d, J = 8, 3H), 2.16 (s, 3H), 2.32 (s, 3H), 2.35 (s, 3H), 2.47 (s, 3H), 3.42 (s, 3H), 3.50-3.60 (m, 2H), 4.50-4.15 (m, 1H) , 6.56 (d, J = 8, 1H), 7.00-7.15 (m, 3H). w) CI-HRMS: Calcd: 355.2134, Found: 355.2134 (M + H); NMR (CDCl3, 300 MHz): 1.05 (t, J = 8, 3H), 1.85 2.00 (m, 2H), 2.17 (s, 3H), 2.36 (s, 6H) , 2.50 (s, 3H), 3.41 (s, 3H), 3.45 (dd, J = 8, 3, 1H), 3.82 (dd, J = 8, 1, 1H), 5.70-5.80 (m, 1H), 7.00-7.20 (m, 3H). x) CI-HRMS: Calcd: 364.2501, Found: 364.2501 (M + H); NMR (CDC13, 300 MHz): 0.35-0.43 (m, 2H), 0.50-0.60 (m, 2H), 0.98 (t, J = 8, 3H), 1.20-1.30 (m, 1H), 1.72-1.90 (m, 2H), 2.18 (s, 3H) 2.28 (s, 3H), 2.35 (s, 3H), 2.40 (s, 3H), 3.88-4.03 (m, 2H), 4.03-4.20 (m, 2H), 7.00-7.15 (m, 3H). y) CI-HRMS: Calcd: 353.2454, Found: 353.2454 (M + H); Analysis: Calcd: C: 68.15; H: 8.02; N: 23.84; Found: C: 67.43; H: 7.81; N: 23.45; NMR (CDCl3, 300 MHz): 1.38 (d, J = 8, 3H), 2.18 (s, 3H), 2.30-2.40 (m, 12H), 2.47 93, 3H), 2.60-2.75 (m, 2H), 4.30-4.50 (m, 1H), 6.60-6.70 (m, 1H), 7.00-7.15 (m, 3H). z) CI-HRMS: Calcd: 361.2140, Found: 361.2128 (M + H); NMR (CDC13, 300 MHz): 0.75-0.83 (m, 2H), 1.00-1.10 (m, 2H), 2.17 (s, 3H), 2.30 (s, 3H), 2.36 (s, 3H), 2.47 (s, 3H), 2.85 (t, J = 8, 2H), 3.30-3.40 (m, 1H), 4.40-4.55 (m, 2H), 7.00-7.18 (m, 3H). aa) CI-HRMS: Calcd: 363.2297, Found: 363.2311 (M + H); NMR (CDC13, 300 MHz): 1.01 (t, 3H, J=8), 1.75-1.90 (m,2H), 2.15 (s,3H), 2.19 (s, 3H), 2.35 (s, 3H), 2.40 (s, 3H), 2.40 (s, 3H), 2.98 (t, 2H, J = 8), 3.97-4.15 (m, 2H), 4.15-4.30 (m, 2H), 7.03(d, 1H, 1H), 7.08 (d, 1H, J = 8), 7.10 (s, 1H). ab) CI-HRMS: Calcd: 363.2297, Found: 363.2295 (M + H); NMR (CDCl3, 300 MHz): 1.01 (t, 3H, J = 8), 1.35 1.55 (m, 2H), 1.75-1.90 (m, 2H), 2.15 (s, 3H), 2.30 (s, 3H), 2.36 (s, 3H), 2.46 (s, 3H), 4.10-4.30 (m, 2H), 4.95-5.10 (br s, 2H), 7.05 (d, 1H, J = 8), 7.10 (d, 1H, J = 8), 7.15 ( s, 1H). ac) CI-HRMS: Calcd: 368.2450, Found: 368.2436; Analysis: Calcd: C, 68.62, H, 7.95, N, 19.06; Found: C, 68.73, H, 7.97, N, 19.09; NMR (CDC13, 300 MHz) : 1.05 (t, J = 8, 3H), 1.70-1.90 (m, 2H), 2.01 (d, J = 3, 6H), 2.20 (s, 3H), 2.30 (s, 3H), 2.46, 2.465 (s, s, 3H), 3.42, 3.48 (s, s, 3H), 3.53-3.63 (m, 2H), 4.35-4.45 (m, 1H), 6.73 (d, J = 8, 1H), 6.97 (s, 2H). (ad) CI- HRMS: Calcd: 352.2501, Found: 352.2500 (M + H): Analysis: Calcd: C: 71.76; H: 8.33; N: 19.92, Found: C: 71.55; H: 8.15; N: 19.28; NMR (CDCl3, 300 MHz): 1.01(t, J = 8, 6H), 1.58 -1.70 (m, 2H), 1.70-1.85 (m, 2H), 2.02 (s, 6H), 2.19 (s, 3H), 2.45 (s, 3H), 4.12-4.28 (m, 1H), 6.18 (d, J = 8, 1H), 6.95 (s, 2H). (ae) CI- HRMS: Calcd: 398.2556, Found: 398.2551 (M + H); Analysis: Calcd: C: 66.47; H: 7.86; N: 17.62, Found: C: 66.74; H: 7.79; N: 17.70; NMR (CDCl3, 300 MHz): 2.00 (s, 6H), 2.12 (s, 3H), 2.30 (s, 3H), 2.37 (s, 3H), 3.40 (s, 6H), 3.78 (t, J = 8, 4H), 4.25-4.40 (m, 4H), 6.93 (s, 2H). (af) CI-HRMS: Calcd: 450.1141, Found: 450.1133 (M + H); Analysis: Calcd: C: 50.67; H: 5.37; N: 15.55; Br: 17.74; Found: C: 52.36; H: 5.84; N: 14.90; Br: 17.44; NMR (CDCl3, 300 MHz): 2.32 (s, 3H), 2.57 (s, 3H), 3.42 (s, 6H), 3.60 (q, J = 8, 2H), 3.69 (q, J = 8, 2H), 3.82 (s, 3H), 4.60-4.70 (m, 1H), 6.73 (d, J = 8, 1H), 6.93 (dd, J = 8, 1, 1H), 7.22 (d, J = 8, 1H). ag) CI-HRMS: Calcd: 434.1192, Found: 434.1169 (M + H); Analysis: Calcd: C: 52.54; H: 5.58; N: 16.12; Br: 18.40; Found: C: 52.57; H: 5.60; N: 15.98; Br: 18.22; NMR (CDC13, 300 MHz): 1.00-1.07 (m, 3H), 1.65-1.85 (m, 2H), 2.35 (s, 3H), 2.46, 2.47 (s, s, 3H), 3.40, 3.45 (s, s, 3H), 3.83 (s, 3H), 4.35-4.45 (m, 1H), 6.55 (d, J = 8, 1H), 6.92 (dd, J = 8, 1, 1H), 7.20 7.30 (m, 2H). ah) CI-HRMS: Calcd: 337.2266, Found: 337.2251 (M + H); Analysis: Calcd: C: 70.18; H: 8.06; N: 20.75; Found: C: 70.69; H: 7.66; N: 20.34; NMR (CDCl3, 300 MHz): 1.35 (t, J = 8, 6H), 2.01 (s, 6H), 2.15 (s, 3H), 2.30 (s, 3H), 2.38 (s, 3H), 4.07 (q, J = 8, 4H), 6.93 (s, 2H). ai) CI-HRMS: Calcd: 412.2713, Found: 412.2687 (M + H); Analysis: Calcd: C: 67.13; H: 8.08; N: 17.02; Found : C: 67.22; H: 7.85; N: 17.13; NMR (CDCl3, 300 MHz):1.24 (t, J = 8, 6H), 2.00 (s, 6H), 2.20 (s, 3H), 2.30 (s, 3H), 2.43 (s, 3H), 3.60 (q, J = 8, 4H), 3.66 (dd, J = 8, 3, 2H), 3.75 (dd, J = 8, 3, 2H), 4.55-4.65 (m, 1H), 6.75 (d, J = 8, 1H), 6.95 (s, 2H). aj) CI-HRMS: Calcd: 398.2556, Found: 398.2545 (M + H); Analysis: Calcd: C: 66.47; H: 7.86; N: 17.62; Found: C: 66.87; H: 7.62; N: 17.75; NMR (CDCl3, 300 MHz): 1.95-2.10 (m, 8H), 2.20 (s, 3H), 2.32 (s, 3H), 2.44 (s, 3H), 3.38 (s, 3H), 3.42 (s, 3H), 3.50-3.70 (m, 4H), 4.58-4.70 (m, 1H), 6.87 (d, J = 8, 1H), 6.95 (s, 2H). ak) CI-HRMS: Calcd: 338.1981, Found: 338.1971 (M + H); Analysis: Calcd: C: 67.63; H: 6.87; N: 20.06; Found: C: 67.67; H: 6.82; N: 20.31; NMR (CDCl3, 300 MHz): 2.15 (s, 3H), 2.29 (s, 3H), 2.35 (s, 3H), 2.43 (s, 3H), 3.90 (t, J = 8, 4H), 4.35-4.45 (m, 4H), 7.00-7.15 (m, 3H). al) CI-HRMS: Calcd: 464.1297, Found: 464.1297 (M + H); NMR (CDCl3, 300 MHz): 2.28 (s, 3H), 2.40 (s, 3H), 3.40 (s, 6H), 3.75 (t, J = 8, 4H), 3.83 (s, 3H), 4.20-4.50 (m, 4K), 6.93 (dd, J = 8, 1, 1H), 7.20 (s, lH), 7.24 (d, J = 1, 1H) am) CI-HRMS: Calcd: 418.1242, Found: 418.1223 (M + H); NMR (CDCl3, 300 MHz): 1.00 (t, d, J = 8, 1, 6H), 1.55-1.75 (m, 4H), 2.34 (s, 3H), 2.49 (s, 3H), 2.84 (s, 3H), 4.15-4.27 (m, 1H), 6.19 (d, J = 8, 1H), 6.93 (dd, J = 8, 1, lH), 7.21-7.30 (m, 2H). an) CI-HRMS: Calcd: 404.1086, Found: 404.1079(M + H); NMR (CDCl3, 300 MHz): 1.35 (t, J = 8, 6H), 2.28 (s, 3H), 2.40 (s, 3H), 3.83 (s, 3H), 3.90-4.08 (m, 2H), 4.08-4.20 (m, 2H), 6.92 (dd, J = 8, 1, 1H), 7.20 7.25 (m, 2H). ao) CI-HRMS: Calcd: 308.1875, Found: 308.1872 (M + H); NMR (CDCl3, 300 MHz): 0.75-0.80 (m, 2H), 0.93-1.00 (m, 2H), 2.16 (s, 3H), 2.28 (s, 3H), 2.35 (s, 3H), 2.53 (s, 3H), 3.00-3.10 (m, 1H), 6.50-6.55 (m, 1H), 7.00-7.15 (m, 3H). ap) CI-HRMS: Calcd: 397.1988, Found: 397.1984 (M + H); NMR (CDCl3, 300 MHz): 2.43 (s, 3H), 2.50 (s, 3H), 3.43 (s, 3H), 3.61 (dd, J = 8, 8, 2H), 3.69 (dd,J = 8, 8, 2H), 3.88 (s, 3H), 4.58-4.70 (m, 1H), 6.75 (d, J = 8, 1H), 7.20 (dd, J = 8, 1, 1H), 7.25 (d, J = 1, 1H), 7.40 (s, 1H) aq) CI-HRMS: Calcd: 375.2297, Found: 375.2286 (M + H); Analysis: Calcd: C: 70.56; H: 7.01; N: 22.44; Found: C: 70.49; H: 6.99; N: 22.45; NMR (CDCl3, 300 MHz): 0.79-0.85 (m, 2H), 1.00-1.05 (m, 1H), 2.00 (s, 6H), 2.19 (s, 3H), 2.32 (s, 3H), 2.44 (s, 3H), 2.84 (t, J = 8, 2H), 3.30-3.40 (m, 1H), 4.50 (t, J = 8, 2H), 6.95 (s, 2H). ar) CI-HRMS: Calcd: 434.1192, Found: 434.1189 (M + H); Analysis: Calcd: C: 52.54; H: 5.58; N: 16.12; Br: 18.40; Found: C: 52.75; H: 5.59; N: 16.09; Br: 18.67; NMR (CDCl3, 300 MHz): 2.19 (s, 3H), 2.30 (s, 3H), 2.47 (s, 3H), 3.43 (s, 6H), 3.60 (dd, J = 8, 8, 2H), 3.70 (dd, J = 8,8, 2H), 4.58-4.70 (m, 1H), 6.71 (d, J = 8, 1H), 7.08 (d, J = 8, 1H), 7.37 (dd, J = 8, 1, 1H), 7.45 (d, J = 1, 1H). as) CI-HRMS: Calcd: 448.1348, Found: 448.1332 (M + H); Analysis: Calcd: C: 53.58; H: 5.85; N: 16.62; Br: 17.82; Found: C: 53.68; H: 5.74; N: 15.52; Br: 13.03; NMR (CDCl3, 300 MHz): 1.95-2.10 (m, 2H), 2.20 (s, 3H), 2.30 (s, 3H), 2.47 (s, 3H), 3.38 (s, 3H), 3.41 (s, 3H), 3.50-3.67 (m, 4H), 4.55-4.70 (m, 1H), 6.89 (d, J = 8, 1H), 7.05 (d, J = 8, 1H), 7.35 (dd, J = 8, 1, 1H), 7.47 (d, J = 1, 1H) at) CI-HRMS: Calcd: 400.2349, Found: 400.2348 (M + H); Analysis: Calcd: C: C: 63.14; H: 7.32; N: 17.53; Found: C:63.40; H: 7.08; N: 17.14; NMR (CDCl3, 300 MHz): 2.16 (s, 3H), 2.20 (s, 3H), 2.30 (s, 3H), 2.46 (s, 3H), 3.42 (s, 6H), 3.60 (q, J = 8, 2H), 3.70 (q, J = 8, 2H), 3.85 (s, 3H), 4.59-4.70 (m, 1H), 6.70 (d, J = 8, 1H), 6.76 (s, 1H), 6.96 (s, 1H). au) CI-HRMS: Calcd: 414.2505, Found: 414.2493 (M + H); NMR (CDCl3, 300 MHz): 2.15 (s, 3H), 2.19 (s, 3H), 2.25 (s, 3H), 2.40 (s, 3H), 3.40 (s, 6H), 3.76 (t, J = 8, 4H), 3.84 (s, 3H), 4.20-4.45 (m, 4H), 6.77 (s, 1H), 6.93 (s, 1H). av) CI-HRMS: Calcd: 368.2450, Found: 368.2447 (M + H); NMR (CDCl3, 300 MHz): 1.00 (t, J = 8, 6H), 1.55 1.85 (m, 4H), 2.19 (s, 3H), 2.20 (s, 3H), 2.30 (s, 3H), 2.47 (s, 3H), 3.88 (s, 3H), 4.10-4.30 (m, 1H), 6.15 (d, J = 8, 1H), 6.78 (s, 1H), 6.98 (s, 1H). aw) CI-HRMS: Calcd: 353.2216, Found: 353.2197 (M + H); NMR (CDCl3, 300 MHz): 1.35 (t, J = 8, 6H), 2.17 (s, 3H), 2.19 (s, 3H), 2.28 (s, 3H), 2.40 (s, 3H), 3.85 (s, 3H), 3.90-4.20 (m, 4H), 6.78 (s, 1H), 6.95 (s, 1H). ax) CI-HRMS: Calcd: 390.1697, Found: 390.1688 (M + H); Analysis: Calcd: C: 58.53; H: 6.20; N: 17.96; Cl: 9.09; Found: C: 58.95; H: 6.28; N: 17.73; Cl: 9.15; NMR (CDCl3, 300 MHz): 2.35 (s, 3H), 2.37 (s, 3H), 2.48 (s, 3H), 3.42 (s, 6H), 3.60 (dd, J = 8, 8, 2H) 3.68 (dd, J = 8, 8, 2H), 4.59-4.72 (m, 1H), 6.72 (d, J = 8, 1H), 7.12 (d, J = 8, 1H), 7.23 (d, J = 8, 1H), 7.32 (s, 1H). ay) CI-HRMS: Calcd: 374.1748, Found: 374.1735 (M + H); Analysis: Calcd: C: 61.04; H: 6.47; N: 18.73; Cl: 9.48; Found: C: 61.47; H: 6.54; N: 18.23; C1: 9.61; NMR (CDCl3,300 MHz): 1.01 (t, J = 8, 3H), 1.62 1.88 (m, 4H), 2.35 (s, 3H), 2.37 (s, 3H), 2.48 (d, J = 1, 3H), 3.40, 3.45 (s, s, 3H), 3.50-3.64 (m, 2H), 4.38-4.47 (m, 1H), 6.53 (d, J = 8, 1H), 7.12 (d, J = 8, 1H), 7.07 (d, J = 8, 1H), 7.12 (s, 1H). az) CI-HRMS: Calcd: 404.1853, Found: 404.1839 (M + H); NMR (CDCl3, 300 MHz): 2.29 (s, 3H), 2.38 (s, 3H), 2.40 (s, 3H), 3.40 (s, 6H), 3.76 (t, J = 8, 4H), 4.20-4.45 (m, 4H), 7.11 (d, J = 8, 1H), 7.22 (d, J = 8, 1H), 7.31 (s, 1H). ba) CI-HRMS: Calcd: 404.1853, Found: 404.1859 (M + H); Analysis: C: 59.47; H: 6.50; N: 17.34; Cl: 8.79; Found: C: 59.73; H: 6.46; N: 17.10; Cl: 8.73; NMR (CDCl3, 300 MHz): 1.95-2.08 (m, 2H), 2.35 (s, 3H), 2.38 (s, 3H), 2.46 (s, 3H), 3.38 (s, 3H), 3.41 (s, 3H), 3.50-3.65 (m, 4H), 4.56-4.70 (m, 1H), 6.85 (d, J = 8, 1H), 7.12 (d, J = 8, 1H), 7.45 (d, J = 8, 1H), 7.32 (s, 1H). bb) CI-HRMS: Calcd: 391.2246, Found: 391.2258 (M + H); Analysis: C: 67.67; H: 6.71; N: 21.52; Found: C: 67.93; H: 6.70; N: 21.48; NMR (CDC13, 300 MHz): 0.76-0.84 (m, 2H), 0.84-0.91 (m, 2H), 1.00-1.08 (m, 2H), 2.15 (s, 3H), 2.20 (s, 3H), 2.29 (s, 3H), 2.45 (s, 3H), 2.85 (t, J = 8, 2H), 3.28-3.30 (m, 1H), 3.85 (s, 3H), 6.78 (s, 1H), 6.95 (s, 1H). bc, CI-HRMS: Calcd: 386.2192, Found: 386.2181 (M + H); Analysis: C: 62.32; H: 7.06; N: 18.17; Found: C: 62.48; H: 6.83; N: 18.15; NMR (CDCl3, 300 MHz): 7.1 (d, 1H, J = 8), 6.9 (d, 1H, J = 1), 5.8 (dd, 1H, J = 8,1), 6.7 (br.d, 1H, J = 8), 4.7-4.6 (m, 1H), 3.85 (s, 3H), 3.70-3.55 (m, 4H), 3.45 (s, 6H), 2.5 (s, 3H), 2.3 (s, 3H), 2.15 (s, 3H). bd) CI-HRMS: Calcd: 400.2349, Found: 400.2336 (M + H); NMR (CDCl3, 300 MHz): 7.1 (d, 1H, J = 7), 6.85 (d, 1H, J = 1), 6.75 (dd, 1H, J = 7,1), 4.45-4.25 (br.s, 4H), 3.75 (t, 4H, J = 7), 3.4 (s, 6H), 2.4 (s, 3H), 2.25 (s, 3H), 2.15 (s, 3H). be) CI-HRMS: Calcd: 370.2243, Found: 370.2247 (M + H); Analysis: C: 65.02; H: 7.38; N: 18.96; Found: C: 65.28; H: 7.27; N: 18.71; NMR (CDCl3, 300 MHz): 7.1 (d, 1H, J = 8), 6.85 (d, 1H, J = 1), 6.8 (dd, 1H, J = 8,1), 6.5 (br. d, 1H, J = 1), 4.5-4.3 (m, 1H), 3.85 (s, 3H), 3.65-3.5 (m, 2H), 3.4 (s, 2H), 2.5 (s, 3H), 2.3 (s, 3H), 2.2 (s, 3H), 1.9-1.7 (m, 2H), 1.05 (t, 3H, J = 7). bf) CI-HRMS: Calcd: 379.2246, Found: 379.2248 (M + H); NMR (CDCl3, 300 MHz): 7.1 (d, 1H, J = 8), 6.85 (d, 1H, J = 1), 6.8 (dd, 1H, J = 8,1), 4.3-4.0 (m, 4H), 3.85 (s, 3H), 3.0 (t, 2H, J = 7), 2.45 (s, 3H), 2.3 (s, 3H), 2.2 (s, 3H), 1.9-1.8 ( m, 2H), 1.0 (t, 3H, J = 7). bg) CI-HRMS: Calcd: 340.2137, Found: 340.2122 (M + H); NMR (CDCl3, 300 MHz): 7.1 (d, 1H, J = 8), 6.85 (d, 1H, J = 1), 6.75 (dd, 1H, J = 8,1), 4.2-4.0 (br.m, 4H), 3.85 (s, 3H, 2.4 (s, 3H), 2.3 ( s, 3H), 2.2 (s, 3H), 1.35 (t, 6H, J = 7). bh) CI-HRMS: Calcd: 313.1665, Found: 313.6664 (M + H). bi) CI-HRMS: Calcd: 400.2349, Found: 400.2346 (M + H); NMR (CDCl3, 300 MHz): 7.1 (d, 1H, J = 7), 6.9-6.75 (m, 3H), 4.7-4.55 (m, 1H), 3.8 (s, 3H), 3,7-3.5 (m, 4H), 3.45 (s, 3H), 3.35 (s, 3H), 2.5 (s, 3H), 2.3 (s, 3H), 2.2 (s, 3H), 2.1-1.95 (m, 2H). bj) CI-HRMS: Calcd: 377.2090, Found: 377.2092 (M + H); Analysis: C: 67.00; H: 6.44; N: 22.32; Found: C: 67.35; H: 6.44; N: 22.23; NMR (CDCl3, 300 MHz): 7.1 (d, 1H, J = 8), 6.9 (d, 1H, J = 1), 6.8 (dd, 1H, J = 8,1), 4.55-4.4 (m, 2H), 3.85 (s, 3H), 3.4-3.3 (m, 1H), 2.85 (t, 2H, J = 7), 2.5 (s, 3H), 2.3 (s, 3H), 2.2 (s, 3H), 1.1 1.0 (m, 2H), 0.85-0.75 (m, 2H). bk) CI-HRMS: Calcd: 413.2427, Found: 413.2416 (M + H); NMR (CDCl3, 300Hz): 7.1 (d, 1H, J = 8), 6.85 (d, 1H, J = 1), 6.75 (dd, 1H, J = 8;1), 4.6 (m, 1H), 3.85 (s, 3H), 3.75-3.6(m, 4H), 3.6 (q, 4H, J = 7), 2.5 (s, 3H), 2.3 s, 3H), 2.2 (s, 3H), 1.25 (t, 6H, J = 7). bl) CI-HRMS: Calcd: 420.1802, Found: 420.1825(M + H); bm) CI-HRMS: Calcd: 390.1697, Found: 390.1707(M + H); bn) CI-HRMS: Calcd: 397.1465, Found: 397.1462(M + H); bo) CI-HRMS: Calcd: 360.1513, Found: 360.1514(M + H); bp) CI-HRMS: Calcd: 374.1748, Found: 374.1737(M + H); bq) CI-HRMS: Calcd: 479.1155, Found: 479.1154(M + H); br) CI-HRMS: Calcd: 463.1219, Found: 463.1211(M + H); Analysis Calcd: C: 51.96, H: 5.23, N, 15.15, Br: 17.28; Found: C: 52.29, H: 5.62, N: 14.79, Br: 17.47 bs) CI-HRMS: Calcd: 433.1113, Found: 433.1114(M, 79Br); bt) NH3-CI MS: Calcd: 406, Found: 406 (M + NMR (CDCl3, 300 MHz) :6 7.28 (d, J=lOHz, 1H), 7.03 (d, J=8Hz, 1H), 6.96 (s, 1H), 6.7 (d, J=9, 1H), 4.63 (m, 1H), 3.79 (s, 3H), 3.6 (m, 4H), 3.42 (s, 6H), 2.47 (s, 3H), 2.32 (s, 3H). EXAMPLE 431 Preparation of 2,4,7-dimethyl-8-(4-methoxy-2 methylphenyl) [1,5-a]-pyrazolo-1,3,5-triazine (Formula 1, where R3 is CH3, R1 is CH3, Z is C-CH3, Ar is 2,4-dimethylphenyl) 5-Acetamidino-4-(4-methoxy-2-methylphenyl)-3methylpyrazole, acetic acid salt ( 602 mg, 2 mmol) was mixed with a saturated NaHCO3 solution (10 mL). The aqueous mixture was extracted with EtOAc three times. The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo. The residue was taken up in toluene (10 mL) and trimethyl orthoacetate 0.36 g, 3 mmol) was added to the suspension. The reaction mixture was heated to reflux temperature under a nitrogen atmosphere and stirred for 16 hours. After being cooled to ambient temperature, the reaction mixture was concentrated in vacuo to give an oily solid. Column chromatography (CHCl3:MeOH::9:1) afforded, after removal of solvent in vacuo, a yellow viscous oil (Rf = 0.6, 210 mg, 37% yield): NMR (CDCl3, 300 MHz): 7.15 (d, 1H, J = 8), 6.9 (d, 1H, J = 1), 6.85 (dd, 1H, J = 8,1), 3.85 (s, 3H), 2.95 (s, 3H), 2.65 (s, 3H), 2.4 (s, 3H), 2.15 (s, 3H); CI-HRMS: Calcd: 283.1559, Found: 283.1554 (M + H). EXAMPLE 432 7-hydroxy-5-methyl-3-(2-chloro 4-methylphenylOpyrazolo[1,5-a]pyrimidine (Formula 1 where A is CH, R1 is Me, R3 is OH, Z is C-Me, Ar is 2-chloro-4-methylphenyl) 5-Amino-4-(2-chloro-4-methylphenyl)-3methylpyrazole (1.86 g, 8.4 mmol) was dissolved in glacial acetic acid (30 mL) with stirring. Ethyl acetoacetate (1.18 mL, 9.2 mmol) was then added dropwise to the resulting solution. The reaction mixture was then heated to reflux temperature and stirred for 16 hours1 then cooled to room temperature. Ether (100 mL) was added and the resulting precipitate was collected by filtration. Drying in vacuo afforded a white solid 1.0 g, 42% yield): NMR (CDC13, 300Hz): 8.70 (br.s 1H), 7.29 ( s, 1H), 7.21-7.09 ( m, 2H), 5.62 (s, 1H), 2.35 (s, 6H), 2.29 (s, 3H); C-I-MS: 288 (M+H) EXAMPLE 433 7-chloro-5-methyl-3-(2-chloro 4-methylphenyl)pyrazolo[1, 5-a]pyrimidine (Formula 1 where A is CH, R1 is Me, R3 is C1, Z is C-Me, Ar is 2-chloro-4-methylphenyl) A mixture of 7-hydroxy-5-methyl-3-(2-chloro-4 methylphenyl)-pyrazolo[1, 5-a]pyrimidine (1.0 g, 3.5 mmol), phosphorus oxychloride (2.7 g, 1.64 mL, 17.4 mmol), N,N-diethylaniline (0.63 g, 0.7 mL, 4.2 mmol) and toluene (20 mL) was stirred at reflux temperature for 3 hours1 then it was cooled to ambient temperature. The volatiles were removed in vacuo. Flash chromatography (EtOAc:hexane::1:2) on the residue gave 7-chloro-5 methyl-3- (2-chloro-4-methylphenyl)-pyrazolo[l,5- a]pyrimidine (900 mg, 84% yield) as a yellow oil: NMR (CDC13, 300Hz): 7.35 (s, 1H), 7.28-7.26 (m, 1H), 71.6 d, 1H, J = 7), 6.80 (s, 1H), 2.55 (s, 3H), 2.45 (s, 3H), 2.40 (s, 3H); CI- MS: 306 (M+H) EXAMPLE 434 7-(pentyl-3-amino)-5-methyl-3-(2-chloro 4-methylphenyl)pyrazolo[l,5-a]pyrimidine (Formula 1 where A is CH, R1 is Me, R3 is pentyl-3 amino, Z is C-Me1 Ar is 2-chloro-4-methylphenyl) A solution of 3-pentylamine (394mg, 6.5 mmol) and 7-chloro-5-methyl-3-(2-chloro-4methylphenyl)pyrazolo[1,5-a]pyrimidine (200 mg, 0.65 mmol) in dimethylsulfoxide (DMSO, 10 mL) was stirred at 150 C for 2 hours; then it was cooled to ambient temperature. The reaction mixture was then poured onto water (100 mL) and mixed Three extractions with dichloromethane, washing the combined organic layers with brine, drying over MgSO4, filtration and removal of solvent in vacuo produced a yellow solid. Flash chromatography (EtOAc:hexanes: :1:4) afforded a white solid (140 mg, 60% yield): mp 139-1410C; NMR (CDCl3, 300Hz):7.32 (s, 1H), 7.27 (d, 1H, J = 8), 7.12 (d, 1H, J = 7), 6.02 (d, 1H, J = 9), 5.78 ( s, 1H), 3.50-3.39 (m, 1H), 2.45 (s, 3H), 2.36 (s, 6H), 1.82-1.60 (m, 4H), 1.01 (t, 6H, J = 8); Analysis Calcd for C20K25C1N4: C, 67.31, H, 7.06, N, 15.70, Cl: 9.93; Found: C, 67.32, H, 6.95, N, 15.50, Cl, 9.93. The examples delineated in TABLE 2 may be prepared by the methods outlined in Examples 1A, 1B, 432, 433, 434. Commonly used abbreviations are: Ph is phenyl, Pr is propyl, Me is methyl, Et is ethyl, Bu is butyl, Ex is Example, EtOAc is ethyl acetate. TABLE 2 EMI136.1 Ex. Z R3 Ar mp( C) 435b C-Me N(CH2CH2OMe)2 2,4-C12-Ph 71-73 436c C-Me N(Bu)Et 2,4-C12-Ph 86-87 437d C-Me NHCH(Et)CH2OMe 2,4-C12-Ph 110-111 438e C-Me N(Pr)CH2CH2CN 2,4-C12-Ph 83-85 439f C-Me NH-3-pentyl 2,4-C12-Ph 175-176 440g C-Me NHCH(CH2OMe)2 2,4-C12-Ph 107 441h C-Me NHCH(Et)2 2,4-Me2-Ph oil 442i C-Me NHCH(CH2OMe)2 2,4-Me2-Ph 103-105 443j C-Me N(CH2cH2OMe)2 2,4-Me2-Ph 87-89 444k C-Me N(c-Pr)CH2CH2CN 2,4-Me2-Ph 133(dec) 4451 C-Me N(CH2CH2oMe)2 2-C1,4-MePh 77-78 446m C-Me NHCH(CH20Me)2 2-C1,4-MePh 131-133 447n C-Me NHCH(Et)2 2-C1,4-MePh 139-141 4480 C-Me NEt2 2, 4-Me2-Ph 92-94 449P C-Me N(Pr)CH2CH2CN 2,4-Me2-Ph 143-144 450q C-Me N(Bu)CH2CH2CN 2,4-Me2-Ph 115-117 451r C-Me NHCH(Et)CH2OMe 2,4-Me2-Ph oil 4529 C-Me NHCH(Et)2 2-Me,4-MeOPh 104-106 453t C-Me NHCH(CH2OMe)2 2-Me,4-MeOPh 115-116 454u C-Me N(CH2CH2OMe)2 2-Me,4-MeOPh oil 455" C-Me (S)-NHCH(CH2CH2OMe)- 2-Me,4-MeOPh oil (CH20Me) 456w C-Me (S)-NHCH(CH2CH2OMe)- 2,4-Me2-Ph oil (CH2OMe) 457x C-Me N(CH2cH2OMe)2 2-Me,4-ClPh oil 458Y C-Me NHEt 2,4-Me2-Ph oil 459z C-Me NHCH(Et)2 2-Me, 4-ClPh 94-96 460aa C-Me NHCH(CH2OMe)2 2-Me,4-ClPh 113-114 461ab C-Me N(Ac)Et 2,4-Me2-Ph oil 462aC C-Me (S)-NHCH(CH2CH2OMe)- 2-Me,4-ClPh oil (CH2OMe) 463ad C-Me N(Pr)CH2CH2CN 2-Me, 4-MeOPh 118-119 464ae C-Me NEt2 2-Me,4-MeOPh 97-99 465af C-Me (S)-NHCH(CH2CH2OMe) - 2-C1,4-MePh 101-103 (CH2OMe) 466ag C-Me NEt2 2-C1,4-MePh 129-130 467ah C-Me N(c-Pr)CH2CH2CN 2-Me,4-MeOPh 177-178 468ai C-Me N(c-Pr)CH2CH2CN 2-C1,4-MePh 162-163 469aj C-Me NHCH(Et)CH2OMe 2-Me,4-MeOPh oil 470ak C-Me NHCH(Et)CH2OMe 2-C1,4-MePh 111-113 471 C-Me NHCH(CH2OMe)2 2-C1-4-MeOPh 472 C-Me N(CH2CH2OMe)2 2-C1-4-MeOPh 473 C-Me NHCH(Et)CH20Me 2-C1-4-MeOPh 474 C-Me N(c-Pr)CH2CH2CN 2-C1-4-MeOPh 475 C-Me NEt2 2-C1-4-MeOPh 476 C-Me NH-3-pentyl 2-C1-4-MeOPh 477 C-Me NHCH(Et)CH2CH2OMe 2-C1-4-MeOPh 478 C-Me NHCH(Me)CH2CH2OMe 2-C1-4-MeOPh 479 C-Me NHcH(Et)cH2cH2oMe 2-Br-4-MeOPh 480 C-Me NHCH(Me)CH2CH2OMe 2-Br-4-MeOPh 481 C-Me NHCH(Et)CH2CH2OMe 2-Me-4-MeOPh 482 C-Me NHCH(Me)CH2CH2OMe 2-Me-4-MeOPh 483 C-Me NHCH(CH2OMe)2 2-C1-4,5-(Me0)2Ph 484 C-Me N(CH2CH2OMe) 2 2-C1-4,5-(Me0)2Ph 485 C-Me NHCH(Et)CH20Me 2-Cl-4,5-(MeO)2Ph 486 C-Me N(c-Pr)CH2CH2CN 2-Cl-4,5-(MeO)2Ph 487 C-Me NEt2 2-Cl-4,5-(MeO)2Ph 99-101 488 C-Me NH-3-pentyl 2-Cl-4,5-(MeO)2Ph 169-170 489 C-Me NHCH(Et)CH2CH2OMe 2-Cl-4,5-(MeO)2Ph 490 C-Me NHCH(Me)CH2CH20Me 2-Cl-4,5-(MeO)2Ph 491 C-Me NHCH(cH2OMe)2 2-Br-4,5-(MeO)2Pb 90-93 492 C-Me N(CH2CH2OMe)2 2-Br-4,5-(MeO)2Ph 110 493 C-Me NHCH(Et)CH2OMe 2-Br-4,5-(MeO)2Ph 494 C-Me N(c-Pr)CH2CH2CN 2-Br-4,5-(MeO)2Ph 495 C-Me NEt2 2-Br-4,5-(MeO)2Pb 496 C-Me NH-3-pentyl 2-Br-4,5-(MeO)2Ph 497 C-Me NHCH(Et)CH2CH20Me 2-Br-4,5-(MeO)2Ph 493 C-Me NHCH(Me)CH2CH2OMe 2-Br-4,5-(MeO) 2Ph 499 C-Me NHCH(CH2OMe)2 2-Cl-4,6-(MeO)2Ph 500 C-Me N(CH2CH2OMe)2 2-Cl-4,6-(MeO)2Ph 501 C-Me NHCH(Et)CH2OMe 2-Cl-4,6-(MeO)2Ph 502 C-Me N(c-Pr)CH2CH2CN 2-C1-4,6-(MeO)2Ph 503 C-Me NEt2 2-Cl-4,6-(MeO)2Ph 504 C-Me NH-3-pentyl 2-Cl-4,6-(MeO)2Ph 505 C-Me NHcH(Et)cH2cH2oMe 2-Cl-4,6-(MeO)2Ph 506 C-Me NHCH(Me)CH2CH2OMe 2-Cl-4,6-(MeO)2Ph 507 C-Me NHCH(CH2OMe)2 2-Me-4,6-(Me0)2Ph 508 C-Me N(CH2CH2OMe)2 2-Me-4,6-(MeO)2Ph 509 C-Me NHCH(Et)CH2OMe 2-Me-4,6-(MeO)2Ph 510 C-Me N(c-Pr)CH2CH2CN 2-Me-4,6-(Me0)2Ph 511 C-Me NEt2 2-Me-4,6-(MeO)2Ph 512 C-Me NH-3-pentyl 2-Me-4,6-(Me0)2Ph 513 C-Me NHCH(Et)CH2CH20Me 2-Me-4,6-(MeO)2Ph 514 C-Me NHCH(Me) CH2CH20Me 2-Me-4,6-(MeO)2Ph 515 C-Me N(c-Pr)CH2CH2CN 2-Br-4,6-(MeO)2Ph 516 C-Me NEt2 2-Br-4,6-(MeO)2Ph 517 C-Me NH-3-pentyl 2-Br-4,6-(MeO)2Ph 518 C-Me NHCH(Et)CH2CH2OMe 2-Br-4,6-(MeO)2Ph 519 C-Me NHCH(Me)CH2CH2OMe 2-Br-4,6-(MeO)2Ph 520 C-Me NHCH(Et)CH2CH20Me 2-Me-4-MeOPh 521 C-Me NHCH(Me)CH2CH20Me 2-Me-4-MeOPh 522 C-Me NHCH(CH2OMe)2 2-MeO-4-MePh 523 C-Me N(CH2CH2OMe)2 2-MeO-4-MePh 524 C-Me NHCH(Et)CH2OMe 2-Me0-4-MePh 525 C-Me N(c-Pr)CH2CH2CN 2-MeO-4-MePh 526 C-Me NEt2 2-Me0-4-MePh 527 C-Me NH-3-pentyl 2-MeO-4-MePh 528 C-Me NHCH(Et)CH2CH2OMe 2-MeO-4-MePh 529 C-Me NHCH(Me)CH2CH2OMe 2-MeO-4-MePh 530 C-Me NHCH(CH2OMe)2 2-MeO-4-MePh 531 C-Me N(CH2CH2OMe)2 2-MeO-4-MePh 532 C-Me NHCH(Et)CH2OMe 2-Me0-4-MePh 533 C-Me N(c-Pr) CH2CH2CN 2-MeO-4-MePh 534 C-Me NEt2 2-Me0-4-MePh 535 C-Me NH-3-pentyl 2-MeO-4-MePh 536 C-Me NHCH(Et)CH2CH20Me 2-MeO-4-MePh 537 C-Me NHCH(Me)CH2CH20Me 2-MeO-4-MePh 538 C-Me NHCH(CH2OMe)2 2-MeO-4-Olph 539 C-Me N(CH2CH20Me)2 2-Me0-4-ClPh 540 C-Me NHCH(Et)CH2OMe 2-MeO-4-OlPh 541 C-Me N(c-Pr)CH2CH2CN 2-Me0-4-ClPh 542 C-Me NEt2 2-MeO-4-OlPh 543 C-Me NH-3-pentyl 2-Me0-4-ClPh 544 C-Me NHCH(Et)CH2CH2OMe 2-MeO-4-0lPh 545 C-Me NHCH(Me)CH2CH2OMe 2-Me0-4-ClPh NOTES FOR TABLE 2: b) CI-HRMS: Calcd: 423.1355; Found: 423.1337 (M + H). c) Analysis: Calcd: C, 61.38, H, 6.18, N, 14.32: Found: C, 61.54, H, 6.12, N, 14.37. d) Analysis: Calcd: C: 58.02, H, 5.65, N, 14.24; Found: C, 58.11, H, 5.52, N, 14.26. e) Analysis: Calcd: C, 59.71, H, 5.26, N, 14.85; Found: C, 59.94, H, 5.09, N, 17.23. f) Analysis: Calcd: C, 60.48, H, 5.89, N, 14.85, Found: C, 60.62, H, 5.88, N, 14.82. h) CI-HRMS: Calcd: 337.2388; Found: 337.2392 (M + H). i) Analysis: Calcd: C, 68.45, H, 7.669, N, 15.21, Found: C, 68.35, H, 7.49 N, 14.91. j) Analysis: Calcd: C, 69.08, H, 7.915, N, 14.65, Found: C, 68.85, H, 7.83, N, 14.54. k) Analysis: Calcd: C, 73.51, H, 7.01, N, 19.48, Found: C, 71.57, H, 7.15, N, 19.12. 1) CI-HRMS: Calcd: 403.1899; Found: 403.1901 (M + H). m) Analysis: Calcd: C, 61.77, H, 6.49, N, 14.41, C1. 9.13; Found: C, 61.90, H, 6.66, N, 13.62, C1, 9.25. n) Analysis: Calcd: C, 67.31, H, 7.06, N, 15.70, C1. 9.93; Found: C, 67.32, H, 6.95, N, 15.50, C1, 9.93. O) Analysis: Calcd: C, 74.50, H, 8.14, N, 17.38, Found: C, 74.43, H, 7.59, N, 17.16. p) Analysis: Calcd: C, 73.10, H, 7.54, N, 19.37, Found: C, 73.18, H, 7.59, N, 18.81. q) Analysis: Calcd: C, 73.57, H, 7.78, N, 18.65, Found: C, 73.55, H, 7.79, N, 18.64. r) CI-HRMS: Calcd: 353.2333; Found: 353.2341 (M + H). s) Analysis: Calcd: C, 71.56, H, 8.02, N, 15.90, Found: C, 71.45, H,-7.99, N, 15.88. t) Analysis: Calcd: C, 65.60, H, 7.34, N, 14.57, Found: C, 65.42, H, 7.24, N, 14.37. u) CI-HRMS: Calcd: 399.2398; Found: 399.2396 (M + H). v) CI-HRMS: Calcd: 399.2398; Found: 399.2396 (M + H). w) CI-HRMS: Calcd: 383.2450; Found: 383.2447 (M + H). x) 0I-HRMS: Calcd: 403.1887; Found: 403.1901 (M + H). y) CI-HRMS: Calcd: 295.1919; Found: 295.1923 (M + H). z) Analysis: Calcd: C, 67.31, H, 7.06, N, 15.70, Found: C, 67.12, H, 6.86, N, 15.53. aa) Analysis: Calcd: C, 61.77, H, 6.49, N, 14.41, C1, 9.13; Found: C, 62.06, H, 6.37, N, 14.25, C1, 9.12. *ab) CI-HRMS: Calcd: 337.2017; Found: 337.2028 (M + H). ac) CI-HRMS: Calcd: 403.1893; Found: 403.1901 (M + H). ad) Analysis: Calcd: C, 70.00, H, 7.22, N, 18.55, Found: C, 70.05, H, 7.22, N, 18.36. ae) Analysis: Calcd: C, 70.98, H, 7.74, N, 16.55, Found: C, 71.15, H,7.46, N, 16.56. ag) Analysis: Calcd: C, 66.59, H, 6.76, N, 16.34, Found: C, 66.69, H,6.82, N, 16.20. ah) Analysis: Calcd: C, 70.38, H, 6.71, N, 18.65, Found: C, 70.35, H,6.82, N, 18.83. ai) Analysis: Calcd: C, 66.39, H, 5.85, N, 18.44, C1, 9.33; Found: C, 66.29, H, 5.51, N, 18.36, C1, 9.31. aj) CI-HRMS: Calcd: 369.2278; Found: 369.2291 (M + H). at) Analysis: Calcd: C, 64.42, H, 6.77, N, 15.02, Found: C, 64.59, H,6.51, N, 14.81. The examples delineated in TABLE 3 may be prepared by the methods outlined in Examples 1, 2, 3 or 6. Commonly used abbreviations are: Ph is phenyl, Pr is propyl, Me is methyl, Et is ethyl1 Bu is butyl, Ex is Example. TABLE 3 EMI141.1 Ex. Z R3 A@ 546a C-Me NHCH(Et)2 2-Me-4-Me2N-Ph 164-166 547b C-Me S-NHCH(CH2CH2OMe) 2,4-Me2-Ph oil -CH20Me 548c C-Me S-NHCH(CH2CH2OMe) 2-Me-4-Cl-Ph oil -CH20Me 549d C-Me N(C-Pr)0H20H20N 2-Me-4-C1-Ph 115-116 550e C-Me NHCH(Et)CH2CN 2-Me-4-C1-Ph 131-132 551f C-Me N(Et)2 2,3-Me2-4-OMe-Ph oil 552g C-Me N(CH2CH2OMe)CH2CH2OH 2,4-C12-Ph oil 553h C-Me N(CH2CH20Me)2 2,3-Me2-4-OMe-Ph oil 554i C-Me NHCH(Et)2 2,3-Me2-4-OMePh 123-124 555 C-Me N(CH2-c-Pr)Pr 2-Me-4-C1-Ph oil 556k C-Me N(c-Pr)CH2CH2CN 2,3-Me2-4-OMePh 158-160 557 C-Me N(c-Pr)Et 2-Cl-4-OMePH 558 C-Me N(c-Pr)Me 2-C1-4-OMePh 559 C-Me N(c-Pr)Pr 2-C1-4-OMePh 560 C-Me N(c-Pr)Bu 2-C1-4-OMePh 5611 C-Me N(Et)2 2-C1-4-CN-Ph 115-117 562 C-Me N(c-Pr)2 2-C1-4-OMe 127-129 563m C-Me NHCH(CH20H)2 2, 4-C12-Ph 128-129 564 C-Me N(c-Pr)Et 2-Br-4,5-(MeO)2Ph 565 C-Me N(c-Pr)Me 2-Br-4,5-(MeO)2Ph 566 C-Me NH-c-Pr 2-Me-4-MeOPh 126-128 567 C-Me NHCH(Et)CH20H 2-Me-4-MeOPh 60-62 568 C-Me NMe2 2-Br-4,5-(MeO)2Ph 569 C-Me NHCH(Et)2 2-Me-4-MeOPh 103-105 570 C-Me N(c-Pr)Et 2-Me-4-MeOPh 173-174 571 C-Me NH-2-pentyl 2,4-C12-Ph 118-120 572 C-Me NHCH(Et)CH2CN 2,4-C12-Ph 141-142 573 C-Me NHCH(Pr)CH20Me 2,4-C12-Ph 87-88 574 C-Me NHCH(CH2-iPr)CH2OMe 2,4-C12-Ph amorphous 575 C-Me NH-2-butyl 2,4-Me2-Ph oil 576 C-Me NH-2-pentyl 2,4-Me2-Ph oil 577 C-Me NH-2-hexyl 2,4-Me2-Ph oil 578 C-Me NHCH(i-Pr)Me 2,4-Me2-Ph oil 579 C-Me NHCH(Me)CH2-iPr 2, 4-Me2-Ph oil 580 C-Me NHCH(Me)-c-C6H11 2,4-Me2-Ph oil 581 C-Me NH-2-indanyl 2,4-Me2-Ph oil 582 C-Me NH-1-indanyl 2,4-Me2-Ph oil 583 C-Me NHCH(Me)Ph 2,4-Me2-Ph oil 584 C-Me NHCH(Me)CH2-(4-ClPh) 2,4-Me2-Ph oil 585 C-Me NHCH(Me)CH2COCH3 2,4-Me2-Ph oil 586 C-Me NHCH(Ph)CH2Ph 2,4-Me2-Ph oil 587 C-Me NHCH(Me) (CH2)3NEt2 2,4-Me2-Ph oil 588 C-Me NH-(2-Ph-c-C3H4) 2,4-Me2-Ph oil 589 C-Me NHCH(Et)CH2CN 2,4-Me2-Ph 119-120 590 C-Me NH-3-hexyl 2,4-Me2-Ph oil 591n C-Me NEt2 2-Meo-4-clph oil 5920 C-Me NHCH(Et)2 2-MeO-4-ClPh oil 59=p C-Me NHCH(Et)CH2OMe 2-Meo-4-clph oil 594 C-Me NMe2 2-MeO-4-ClPh oil 595q C-Me NHCH(Et) 2 2-OMe-4-MePh oil 596r C-Me NEt2 2-OMe-4-MePh oil 597s C-c-Pr NHCH(CH2OMe)2 2,4-C12-Ph oil 598 C-Me N(c-Pr)Et 2,4-Me2-Ph 599 C-Me N(c-Pr)Et 2,4-C12-Ph 600 C-Me N(c-Pr)Et 2,4,6-Me3-Ph 601 C-Me N(c-Pr)Et 2-Me-4-C1-Ph 602 C-Me N(c-Rr)Et 2-C1-4-Me-Ph 603 C-Me NHCH(c-Pr)2 2,4-C12-Ph 604 C-Me NHCH(c-Pr)2 2,4-Me2-Ph 605 C-Me NHCH(c-Pr)2 2-Me-4-Cl-Ph 606 C-Me NHCH(c-Pr)2 2-C1-4-Me-Ph 607 C-Me NHCH(c-Pr)2 2-Me-4-OMe-Ph 608 C-Me NHCH(c-Pr)2 2-C1-4-OMe-Ph 609 C-Me NHCH(CH2OMe)2 2-C1-5-F-OMePh 610 C-Me NEt2 2-C1-5-F-OMePh 611 C-Me N(c-Pr)CH2CH2CN 2-Cl-5-F-OMePh 612 C-Me NHCH(Et)2 2-C1-5-F-OMePh 613 C-Me N(CH2CH2OMe)2 2-C1-5-F-OMePh 614 C-Me NEt2 2,6-Me2-pyrid-3-yl 615 C-Me N(c-Pr)CH2CH2CN 2,6-Me2-pyrid-3-yl 616 C-Me NHCH(Et)2 2, 6-Me2-pyrid-3-yl 617 C-Me N(CH2CH2OMe)2 2,6-Me2-pyrid-3-yl 618 C-OH NHCH(CH20Me)2 2,4-Me2-Ph 619 C-OH NEt2 2,4-Me2-Ph 620 C-OH N(c-Pr)CH2CH2CN 2,4-Me2-Ph 621 C-OH NHCH(Et)2 2,4-Me2-Ph 623 C-OH N(CH2CH20Me)2 2,4-Me2-Ph 624 C-NEt2 NHCH(cH20Me)2 2,4-Me2-Ph 625 C-NEt2 NEt2 2,4-Me2-Ph 626 C-NEt2 N(c-Pr)CH2CH2CN 2,4-Me2-Ph 627 C-NEt2 NHCH(Et)2 2,4-Me2-Ph 628 C-NEt2 N(CH2CH2OMe)2 2,4-Me2-Ph 629 C-Me NHCH(Et)2 2-Me-4-CN-Ph 63J C-Me N(CH2CH2OMe)2 2-Me-4-CN-Ph Notes for Table 3: a) CI-HRMS: Calcd:367.2610, Found: 367.2607 (M + H); b) CI-HRMS: Calcd:384.2400, Found: 384.2393 (M + H); c) CI-HRMS: Calcd:404.1853, Found: 404.1844 (M + H); d) CI-HRMS: Calcd:381.1594, Found: 381.1596 (M + H); Analysis: Calcd: C: 63.07, H, 5.57, N, 22.07, C1, 9.32; Found: C: 63.40, H, 5.55, N, 21.96, C1: 9.15 e) CI-HRMS: Calcd:369.1594, Found: 369.1576 (M + H); f) CI-HRMS: Calcd:354.2216, Found: 354.2211 (M + H); g) CI-HRMS: Calcd:410.1072, Found: 410.1075 (M + H); h) CI-HRMS: Calcd:414.2427, Found: 414.2427(M + H); i) CI-HRMS: Calcd:368.2372, Found: 368.2372(M + H); j) CI-HRMS: Calcd:384.1955, Found: 384.1947(M + H); k) CI-HRMS: Calcd:391.2168, Found: 391.2160(M + H); 1) CI-HRMS: Calcd:335.1984, Found: 335.1961(M + H); m) CI-HRMS: Calcd:382.0759, Found: 382.0765(M + H); n) NH3-CI MS: Calcd: 360, Found: 360 (M + H)+ o) NH3-CI MS: Calcd: 374, Found: 374 (M + NMR (CDC13, 300 MHz NMR (CDC13, 300 MHz) :6 7.28 (d, J=8Hz, 1H), 7.03 (d, J=8Hz, 1H), 6.96 (s, 1H), 6.52 (d, J=9Hz, lH), 4.36 (m, 1H), 3.8 (s, 3H), 3.55 (m, 2H), 3.39 (s, 3H), 2.47 (s, 3H), 2.32 (s, 3H), 1.76 (m, 2H), 1.01 (t, J=7.32Hz, 3H). q) CI-HRMS: Calcd: 354.2294, Found: 354.2279 (M + H)+ r) CI-HRMS: Calcd: 340.2137, Found: 340.2138 (M + H)+ s) CI-HRMS: Calcd: 436.1307, Found: 436.1296 (M + The examples delineated in TABLE 4 may be prepared by the methods outlined in Examples 1A, 1B, 432, 433, 434. Commonly used abbreviations are: Ph is phenyl, Pr is propyl, Me is methyl, Et is ethyl1 Bu is butyl, Ex is Example, EtOAc is ethyl acetate. TABLE 4 EMI145.1 Ex. Z R 631 C-Me NHCH(Et)2 2-Br-4,5-(MeO)2Ph 160-161 632 C-Me NHCH(Et)2 2-Br-4-MeOPh 110-111 633 C-Me N(CH2CH2OMe)2 2-Br-4-MeOPh 74-76 634 C-Me NHCH(CH2OMe)2 2-Br-4-MeOPh 128-130 635 C-Me N(Et)2 2-Me-4-ClPh 113-114 636 C-Me N(c-Pr)Et 2,4-Cl2Ph 637 C-Me N(c-Pr)Et 2,4-Me2Ph 638 C-Me N(c-Pr)Et 2,4,6-Me3Ph 639 C-Me N(c-Pr)Et 2-Me-4-MeOPh 640 C-Me N(c-Pr)Et 2-C1-4-MeOPh 641 C-Me N(c-Pr)Et 2-C1-4-MePh 642 C-Me N(c-Pr)Et 2-Me-4-ClPh 643 C-Me NHCH(c-Pr)2 2,4-C12-Ph 644 C-Me NHCH(c-Pr)2 2,4-Me2-Ph 645 C-Me NHCH(c-Pr)2 2-Me-4-Cl-Ph 646 C-Me NHCH(c-Pr)2 2-C1-4-Me-Ph 647 C-Me NHCH(c-Pr)2 2-Me-4-OMe-Ph 648 C-Me NHCH(c-Pr)2 2-Cl-4-OMe-Ph 649 C-Me NHCH(CH2OMe)2 2-C1-5-F-OMePh 650 C-Me NEt2 2-Cl-5-F-OMePh 651 C-Me N(c-Pr)CH2CH2CN 2-Cl-5-F-OMePh 652 C-Me NHCH(Et) 2 2-Cl-5-F-OMePh 653 C-Me N(CH2CH20Me)2 2-Cl-5-F-OMePh 654 C-Me NEt2 2,6-Me2-pyrid-3-yl 655 C-Me N(c-Pr)CH2CH2CN 2,6-Me2-pyrid-3-yl 656 C-Me NHCH(Et)2 2,6-Me2-pyrid-3-yl 657 C-Me N(CH2CH20Me)2 2,6-Me2-pyrid-3-yl 658 C-OH NHCH(CH2OMe)2 2,4-Me2-Ph 659 C-OH NEt2 2,4-Me2-Ph 660 C-OH N(c-Pr)CH2CH2CN 2,4-Me2-Ph 661 C-OH NHCH(Et)2 2,4-Me2-Ph 662 C-OH N(CH2CH20Me)2 2,4-Me2-Ph 663 C-NEt2 NHCH(CH2OMe)2 2,4-Me2-Ph 664 C-NEt2 NEt2 2,4-Me2-Ph 665 C-NEt2 N(c-Pr)CH2CH2CN 2,4-Me2-Ph 666 C-NEt2 NHCH(Et)2 2,4-Me2-Ph 667 C-NEt2 N(CH2CH20Me)2 2,4-Me2-Ph 668 C-Me NHCH(Et)2 2-Me-4-CN-Ph 669 C-Me N(CH2CH2OMe)2 2-Me-4-CN-Ph The examples in Tables 5 or 6 may be prepared by the methods illustrated in Examples 1A, 1B, 2, 3, 6, 431, 432, 433, 434 or by appropriate combinations thereof. Commonly used abbreviations are: Ph is phenyl, Pr is propyl, Me is methyl, Et is ethyl1 Bu is butyl, Ex is Example. Table 5 EMI147.1 Ex. R14 R3 Ar 670 Me NHCH(CH2OMe)2 2,4-Cl2-Ph 671 Me NHCHPr2 2,4-C12-Ph 672 Me NEtBu 2,4-C12-Ph 673 Me NPr(CH2-c-C3H5) 2,4-C12-Ph 674 Me N(CH2CH2OMe)2 2,4-C12-Ph 675 Me NH-3-heptyl 2,4-C12-Ph 676 Me NHCH(Et)CH2OMe 2,4-C12-Ph 677 Me NEt2 2,4-C12-Ph 678 Me NHCH(CH2OEt)2 2,4-Cl2-Ph 679 Me NH-3-pentyl 2,4-Cl2-Ph 680 Me NMePh 2,4-Cl2-Ph 681 Me NPr2 2,4-Cl2-Ph 682 Me NH-3-hexyl 2,4-Cl2-Ph 683 Me morpholino 2,4-Cl2-Ph 684 Me N(CH2Ph)CH2CH2OMe 2,4-C12-Ph 685 Me NHCH(CH2Ph)CH2OMe 2,4-C12-Ph 686 Me NH-4-tetrahydropyranyl 2,4-C12-Ph 687 Me NH-cyclopentyl 2, 4-C12-Ph 688 Me OEt 2,4-C12-Ph 689 Me OCH(Et)CH2OMe 2,4-C12-Ph 690 Me OCH2Ph 2,4-C12-Ph 691 Me 0-3-pentyl 2,4-C12-Ph 692 Me SEt 2,4-Cl2-Ph 693 Me S(O)Et 2,4-Cl2-Ph 694 Me SO2Et 2,4-Cl2-Ph 695 Me Ph 2,4-C12-Ph 696 Me 2-CF3-Ph 2,4-Cl2-Ph 697 Me 2-Ph-Ph 2,4-Cl2-Ph 698 Me 3-pentyl 2,4-Cl2-Ph 699 Me cyclobutyl 2,4-Cl2-Ph 700 Me 3-pyridyl 2,4-Cl2-Ph 701 Me CH(Et)CH2CONMe2 2,4-Cl2-Ph 702 Me CH(Et)CH2CH2NMe2 2,4-C12-Ph 703 Me NHCH(cH2OMe)2 2,4,6-Me3-Ph 704 Me NHCHPr2 2,4,6-Me3-Ph 705 Me NEtBu 2,4,6-Me3-Ph 706 Me NPr(CH2-c-C3H5) 2,4,6-Me3-Ph 707 Me N(CH2CH2OMe)2 2,4,6-Me3-Ph 708 Me NH-3-heptyl 2,4,6-Me3-Ph 709 Me NHCH(Et)CH2OMe 2,4,6-Me3-Ph 710 Me NEt2 2,4,6-Me3-Ph 711 Me NHCH(CH2OEt)2 2,4, 6-Me3-Ph 712 Me NH-3-pentyl 2,4,6-Me3-Ph 713 Me NMePh 2,4,6-Me3-Ph 714 Me NPr2 2,4,6-Me3-Ph 715 Me NH-3-hexyl 2,4,6-Me3-Ph 716 Me morpholino 2,4,6-Me3-Ph 717 Me N(CH2Ph)CH2CH2OMe 2,4,6-Me3-Ph 718 Me NHCH(CH2Ph)CH2OMe 2,4,6-Me3-Ph 719 Me NH-4-tetrahydropyranyl 2,4,6-Me3-Ph 720 Me NH-cyclopentyl 2,4,6-Me3-Ph 721 Me OEt 2,4,6-Me3-Ph 722 Me OCH(Et)CH2OMe 2,4,6-Me3-Ph 723 Me OCH2Ph 2,4,6-Me3-Ph 724 Me 0-3-pentyl 2,4,6-Me3-Ph 725 Me SEt 2,4,6-Me3-Ph 726 Me S(O)Et 2,4,6-Me3-Ph 727 Me SO2Et 2,4,6-Me3-Ph 728 Me 0H(0O2Et)2 2,4,6-Me3-Ph 729 Me C(Et) (CO2Et)2 2,4,6-Me3-Ph 730 Me CH(Et)CH2OH 2,4,6-Me3-Ph 731 Me CH(Et)CH2OMe 2,4,6-Me3-Ph 732 Me CONMe2 2,4,6-Me3-Ph 733 Me COCH3 2,4,6-Me3-Ph 734 Me CH(OH)CH3 2,4,6-Me3-Ph 735 Me C(OH)Ph-3-pyridyl 2,4,6-Me3-Ph 736 Me Ph 2,4,6-Me3-Ph 737 Me 2-Ph-Ph 2,4, 6-Me3-Ph 738 Me 3-pentyl 2,4,6-Me3-Ph 739 Me cyclobutyl 2,4,6-Me3-Ph 740 Me 3-pyridyl 2,4,6-Me3-Ph 741 Me CH(Et)CH2CONMe2 2,4,6-Me3-Ph 742 Me CH(Et)CH2CH2NMe2 2,4,6-Me3-Ph 743 Me NHCH(CH2OMe)2 2,4-Me2-Ph 744 Me N(CH2CH2OMe)2 2,4-Me2-Ph 745 Me NHcH(Et)cH2oMe 2,4-Me2-Ph 746 Me NH-3-pentyl 2,4-Me2-Ph 747 Me NEt2 2,4-Me2-Ph 748 Me N(CH2CN)2 2,4-Me2-Ph 749 Me NHCH(Me)CH2OMe 2,4-Me2-Ph 750 Me OCH(Et)CH2OMe 2,4-Me2-Ph 751 Me NPr-c-C3H5 2,4-Me2-Ph 752 Me NHCH(Me)CH2NMe2 2,4-Me2-Ph 753 Me N(c-C3H5)CH2CH2CN 2,4-Me2-Ph 754 Me N(Pr)CH2CH2CN 2,4-Me2-Ph 755 Me N(Bu)CH2CH2CN 2,4-Me2-Ph 756 Me NHCHPr2 2,4-Me2-Ph 757 Me NEtBu 2,4-Me2-Ph 758 Me NPr(CH2-c-C3H5) 2, 4-Me2-Ph 759 Me NH-3-heptyl 2,4-Me2-Ph 760 Me NEt2 2,4-Me2-Ph 761 Me NHCH(CH2OEt)2 2,4-Me2-Ph 762 Me NH-3-pentyl 2,4-Me2-Ph 763 Me NMePh 2,4-Me2-Ph 764 Me NPr2 2,4-Me2-Ph 765 Me NH-3-hexyl 2,4-Me2-Ph 766 Me morpholino 2,4-Me2-Ph 767 Me N(CH2Ph)CH2CH2OMe 2,4-Me2-Ph 768 Me NHCH(CH2Ph)CH2OMe 2,4-Me2-Ph 769 Me NH-4-tetrahydropyranyl 2,4-Me2-Ph 770 Me NH-cyclopentyl 2,4-Me2-Ph 771 Me NHCH(CH2OMe)2 2-Me-4-MeO-Ph 772 Me N(CH2CH2OMe)2 2-Me-4-MeO-Ph 773 Me NHCH(Et)CH2OMe 2-Me-4-MeO-Ph 774 Me N(Pr)CH2CH2CN 2-Me-4-MeO-Ph 775 Me OCH(Et)CH2OMe 2-Me-4-MeO-Ph 776 Me NHCH(CH2OMe)2 2-Br-4-MeO-Ph 777 Me N(CH2CH2oMe)2 2-Br-4-MeO-Ph 778 Me NHCH(Et)CH2OMe 2-Br-4-MeO-Ph 779 Me N(Pr)CH2CH2CN 2-Br-4-MeO-Ph 780 Me OCH(Et) CH2OMe 2-Br-4-MeO-Pb 781 Me NHCH(CH2OMe)2 2-Me-4-NMe2-Ph 782 Me N(CH2CH2OMe)2 2-Me-4-NMe2-Ph 783 Me NHCH(Et)CH2OMe 2-Me-4-NMe2-Ph 784 Me N(Pr)CH2CH2CN 2-Me-4-NMe2-Ph 785 Me OCH(Et)CH2OMe 2-Me-4-NMe2-Ph 786 Me NHCH(CH2OMe)2 2-Br-4-NMe2-Ph 787 Me N(CH2CH2OMe)2 2-Br-4-NMe2-Ph 788 Me NHCH(Et)CH2OMe 2-Br-4-NMe2-Ph 789 Me N(Pr)CH2CH2CN 2-Br-4-NMe2-Ph 790 Me OCH(Et)CH2OMe 2-Br-4-NMe2-Ph 791 Me NHCH(CH2OMe)2 2-Br-4-i-Pr-Ph 792 Me N(CH2CH2OMe)2 2-Br-4-i-Pr-Ph 793 Me NHCH(Et)CH2OMe 2-Br-4-i-Pr-Ph 794 Me N(Pr)CH2CH2CN 2-Br-4-i-Pr-Ph 795 Me OCH(Et)CH2OMe 2-Br-4-i-Pr-Ph 796 Me NHCH(CH2OMe)2 2-Br-4-Me-Ph 797 Me N(CH2cH2OMe)2 2-Br-4-Me-Ph 798 Me NHCH(Et)CH2OMe 2-Br-4-Me-Ph 799 Me NtPr)CH2CH2CN 2-Br-4-Me-Ph 80J Me OCH(Et)CH2OMe 2-Br-4-Me-Ph 801 Me NHCH(CH2OMe) 2 2-Me-4-Br-Ph 802 Me N(CH2CH2OMe)2 2-Me-4-Br-Ph 803 Me NHCH < Et)CH2OMe 2-Me-4-Br-Ph 804 Me N(Pr)CH2CH2CN 2-Me-4-Br-Ph 805 Me OCH(Et)CH2OMe 2-Me-4-Br-Ph 806 Me NHCH(CH2OMe)2 2-Cl-4,6-Me2-Ph 807 Me N(CH2cH2OMe)2 2-Cl-4,6-Me2-Ph 808 Me NHCH(CH2OMe)2 4-Br-2,6-(Me)2-Ph 809 Me N(CH2CH2OMe)2 4-Br-2,6-(Me)2-Ph 810 Me NHCH(CH2OMe)2 4-i-Pr-2-SMe-Ph 811 Me N(CH2CH2OMe)2 4-i-Pr-2-SMe-Ph 812 Me NHCH(CH2OMe)2 2-Br-4-CF3-Ph 813 Me N(CH2CH2OMe)2 2-Br-4-CF3-Ph 814 Me NHCH(CH2OMe)2 2-Br-4,6-(MeO)2-Ph 815 Me N(CH2CH2OMe)2 2-Br-4,6-(MeO)2-Ph 816 Me NHCH(CH2OMe)2 2-C1-4,6-(MeO)2-Ph 817 Me N(CH2CH2OMe)2 2-Cl-4,6-(MeO)2-Ph 818 Me NHCH(CH2OMe)2 2,6-(Me)2-4-SMe-Ph 819 Me N(CH2CH2OMe)2 2,6-(Me) 2-4-SMe-Ph 820 Me NHCH(CH2OMe)2 4-(COMe)-2-Br-Ph 821 Me N(CH2CH2oMe)2 4-(COMe)-2-Br-Ph 822 Me NHCH(CH2OMe)2 2,4,6-Me3-pyrid-3-yl 823 Me N(CH2CH2OMe)2 2,4,6-Me3-pyrid-3-yl 824 Me NHCH(CH2OMe)2 2,4-(Br)2-Ph 825 Me N(CH2CH20Me)2 2,4-(Br)2-Ph 826 Me NHCH(CH2OMe)2 4-i-Pr-2-SMe-Ph 827 Me N(CH2CH2OMe)2 4-i-Pr-2-SMe-Ph 828 Me NHCH(CH2OMe)2 4-i-Pr-2-SO2Me-Ph 829 Me N(CH2cH2OMe)2 4-i-Pr-2-SO2Me-Ph 830 Me NHCH(CH2OMe)2 2,6-(Me)2-4-SMe-Ph 831 Me N(CH2CH2OMe)2 2,6-(Me)2-4-SMe-Ph 832 Me NHCH(CH2OMe)2 2,6-(Me)2-4-SO2Me-Ph 833 Me N(CH2CH2OMe)2 2,6-(Me)2-4-SO2Me-Ph 834 Me NHCH(CH2OMe)2 2-I-4-i-Pr-Ph 835 Me N(CH2CH2OMe)2 2-I-4-i-Pr-Ph 833 Me NHCH(CH2OMe)2 2-Br-4-N(Me)2-6-MeO-Ph 837 Me N(CH2CH2OMe)2 2-Br-4-N(Me) 2-6-MeO-Ph 838 Me NEt2 2-Br-4-MeO-Ph 839 Me NH-3-pentyl 2-Br-4-MeO-Ph 840 Me NHCH(CH2OMe)2 2-CN-4-Me-Ph 841 Me N(C-C3HS)CH2CH2CN 2,4,6-Me3-Ph 842 Me NHCH(CH2CH2OMe)CH2OMe 2-Me-4-Br-Ph 843 Me NHCH(cH2OMe)2 2,5-Me2-4-MeO-Ph 844 Me N(CH2CH2OMe)2 2,5-Me2-4-MeO-Ph 845 Me NH-3-pentyl 2,5-Me2-4-MeO-Ph 846 Me NEt2 2,5-Me2-4-MeO-Ph 847 Me NHCH(CH2OMe)2 2-C1-4-MePh 848 Me NCH(Et)CH2OMe 2-C1-4-MePh 849 Me N(CH2CH2OMe)2 2-C1-4-MePh 850 Me (S)-NHCH(CH2CH2OMe)CH2OMe 2-C1-4-MePh 851 Me N(c-C3H5)CH2CH2CN 2,5-Me2-4-MeOPh 852 Me NEt2 2-Me-4-MeOPh 853 Me OEt 2-Me-4-MeOPh 854 Me (S)-NHCH(CH2CH2OMe)CH2OMe 2-Me-4-MeOPh 855 Me N(c-C3H5)CH2CH2CN 2-Me-4-MeOPh 856 Me NHCH(CH2CH2OEt)2 2-Me-4-MeOPh 857 Me N(c-c3HS)cH2cH2cN 2, 4-Cl2-Ph 858 Me NEt2 2-Me-4-ClPh 859 Me NH-3-pentyl 2-Me-4-ClPh 860 Me N(CH2CH2OMe)2 2-Me-4-ClPh 861 Me NHCH(CH2OMe)2 2-Me-4-ClPh 862 Me NEt2 2-Me-4-C1Ph 863 Me NEt2 2-C1-4-MePh 864 Me NH-3-pentyl 2-cl-4-Meph 865 Me NHCH(CH2OMe)2 2-C1-4-MeOPh 866 Me N(CH2CH2OMe)2 2-C1-4-MeOPh 867 Me NHCH(Et)CH2OMe 2-C1-4-MeOPh 868 Me N(c-Pr)CH2CH2CN 2-Cl-4-MeOPh 869 Me NEt2 2-Cl-4-MeOPh 870 Me NH-3-pentyl 2-C1-4-MeOPh 871 Me NHCH(Et)CH2cH2oMe 2-C1-4-MeOPh 87Z Me NHCH(Me)CH2CH2OMe 2-C1-4-MeOPh 873 Me NHCH(Et)CH2CH2OMe 2-Br-4-MeOPh 874 Me NHCH(Me)CH2CH2OMe 2-Br-4-MeOPh 875 Me NHCH(Et)CH2CH2OMe 2-Me-4-MeOPh 876 Me NHCH(Me)CH2CH2OMe 2-Me-4-MeOPh 877 Me NHCH(cH2OMe) 2 2-C1-4,5-(MeO)2Ph 878 Me N(CH2CH2OMe)2 2-Cl-4,5-(MeO)2Ph 879 Me NHCH(Et)CH2OMe 2-Cl-4,5-(MeO)2Ph 880 Me N(c-Pr)CH2CH2CN 2-C1-4,5-(MeO)2Ph 881 Me NEt2 2-Cl-4,5-(MeO)2Ph 882 Me NH-3-pentyl 2-C1-4,5-(MeO)2Ph 883 Me NHCH(Et)CH2CH2OMe 2-Cl-4,5-(MeO)2Ph 884 Me NHCH(Me)CH2CH2OMe 2-C1-4,5-(MeO)2Ph 885 Me NHCH(CH2OMe)2 2-Br-4,5-(MeO)2Pb 886 Me N(CH2cH2OMe)2 2-Br-4,5-(MeO)2Pb 887 Me NHCH(Et)0H2OMe 2-Br-4,5-(MeO)2Ph 888 Me N(c-Pr)CH2CH2CN 2-Br-4,5-(MeO)2Ph 889 Me NEt2 2-Br-4,5-(MeO)2Ph 890 Me NH-3-pentyl 2-Br-4,5-(MeO)2Ph 891 Me NHCH(CH2oMe)2 2-Cl-4,6-(MeO)2Ph 892 Me N(CH2CH2OMe)2 2-Cl-4,6-(MeO)2Ph 893 Me NEt2 2-Cl-4,6(MeO) 2Ph 894 Me NH-3-pentyl 2-Cl-4,6-(MeO)2Ph 895 Me NHCH(CH2OMe)2 2-Me-4,6-(MeO)2Ph 896 Me N(CH2cH2OMe)2 2-Me-4,6-(MeO)2Ph 897 Me NHCH(Et)CH2OMe 2-Me-4,6-(MeO)2Ph 898 Me NEt2 2-Me-4,6-(MeO)2Ph 899 Me NH-3-pentyl 2-Me-4,6-(MeO)2Ph 900 Me NHCH(Et)CH2CH2OMe 2-Me-4-MeOPh 901 Me NHCH(Me)CH2CH2OMe 2-Me-4-MeOPh 902 Me NHCH(CH2OMe)2 2-MeO-4-MePh 903 Me N(CH2cH2OMe)2 2-MeO-4-MePh 904 Me NHCH(Et)CH2OMe 2-MeO-4-MePh 905 Me N(c-Pr)CH2CH2CN 2-MeO-4-MePh 906 Me NEt2 2-MeO-4-MePh 907 Me NH-3-pentyl 2-MeO-4-MePh 9Cd Me NHCH(Et)CH2CH2OMe 2-MeO-4-MePh 909 Me NHCH(Me)CH2CH2OMe 2-MeO-4-MePh 910 Me NHCH(CH2OMe)2 2-MeO-4-MePh 911 Me N(CH2cH2OMe)2 2-MeO-4-MePh 912 Me NHCH(Et)CH2OMe 2-MeO-4-MePh 913 Me N(c-Pr) CH2CH2CN 2-MeO-4-MePh 914 Me NEt2 2-MeO-4-MePh 915 Me NH-3-pentyl 2-MeO-4-MePh 916 Me NHCH(CH2OMe)2 2-Me0-4-C1Ph 917 Me N(CH2CH2OMe)2 2-MeO-4-ClPh 918 Me NHCH(Et)CH2OMe 2-MeO-4-ClPh 919 Me NEt2 2-MeO-4-0lPb 920 Me NH-3-pentyl 2-Me0-4-ClPh Table 6 EMI155.1 Ex. R14 R3 Ar 921 Me NHCH(CH2OMe)2 2,4-Cl2-Ph 922 Me NHCHPr2 2,4-C12-Ph 923 Me NEtBu 2,4-C12-Ph 924 Me NPr(CH2-c-C3H5) 2,4-C12-Ph 925 Me N(CH2CH2OMe)2 2,4-C12-Ph 926 Me NH-3-heptyl 2,4-C12-Ph 927 Me NHCH(Et)CH2OMe 2,4-C12-Ph 928 Me NEt2 2,4-Cl2-Ph 929 Me NHCH(CH2OEt)2 2,4-Cl2-Ph 930 Me NH-3-pentyl 2,4-C12-Ph 931 Me NMePh 2,4-Cl2-Ph 932 Me NPr2 2,4-Cl2-Ph 933 Me NH-3-hexyl 2,4-Cl2-Ph 934 Me morpholino 2,4-Cl2-Ph 935 Me N(CH2Ph)CH2CH2OMe 2,4-Cl2-Ph 936 Me NHCH(CH2Ph)CH2OMe 2,4-Cl2-Ph 937 Me NH-4-tetrahydropyranyl 2,4-Cl2-Ph 938 Me NH-cyclopentyl 2,4-Cl2-Ph 939 Me OEt 2,4-Cl2-Ph 940 Me OCH(Et)CH2OMe 2,4-Cl2-Ph 941 Me OCH2Ph 2,4-Cl2-Ph 942 Me 0-3-pentyl 2,4-Cl2-Ph 943 Me SEt 2, 4-Cl2-Ph 944 Me S(O)Et 2,4-Cl2-Ph 945 Me SO2Et 2,4-C12-Ph 946 Me Ph 2,4-Cl2-Ph 947 Me 2-CF3-Ph 2,4-Cl2-Ph 948 Me 2-Ph-Ph 2,4-C12-Ph 949 Me 3-pentyl 2,4-C12-Ph 950 Me cyclobutyl 2,4-Cl2-Ph 951 Me 3-pyridyl 2,4-C12-Ph 952 Me CH(Et)CH2CONMe2 2,4-Cl-Ph 953 Me CH(Et)CH2CH2NMe2 2,4-C12-Ph 954 Me NHCH(CH23Me)2 2,4,6-Me3-Ph 955 Me NHCHPr2 2,4,6-Me3-Ph 956 Me NEtBu 2,4,6-Me3-Ph 957 Me NPr(CH2-c-C3Hs) 2,4,6-Me3-Ph 958 Me N(CH2cH2OMe)2 2,4,6-Me3-Ph 959 Me NH-3-heptyl 2,4,6-Me3-Ph 960 Me NHCH(Et)CH2OMe 2,4,6-Me3-Ph 961 Me NEt2 2,4,6-Me3-Ph 962 Me NHCH(CH2OEt)2 2,4,6-Me3-Ph 963 Me NH-3-pentyl 2,4,6-Me3-Ph 964 Me NMePh 2,4,6-Me3-Ph 965 Me NPr2 2,4,6-Me3-Ph 966 Me NH-3-hexyl 2,4, 6-Me3-Ph 967 Me morpholino 2,4,6-Me3-Ph 968 Me N(CH2Ph)CH2CH2OMe 2,4,6-Me3-Ph 969 Me NHCH(CH2Ph)CH2OMe 2,4,6-Me3-Ph 970 Me NH-4-tetrahydropyranyl 2,4,6-Me3-Ph 971 Me NH-cyclopentyl 2,4,6-Me3-Ph 972 Me OEt 2,4,6-Me3-Ph 973 Me OCH(Et)CH2OMe 2,4,6-Me3-Ph 974 Me OCH2Ph 2,4,6-Me3-Ph 975 Me 0-3-pentyl 2,4,6-Me3-Ph 976 Me SEt 2,4,6-Me3-Ph 977 Me S(O)Et 2,4,6-Me3-Ph 978 Me SO2Et 2,4,6-Me3-Ph 979 Me CH(CO2Et)2 2,4,6-Me3-Ph 980 Me 0(Et) (0O2Et)2 2,4,6-Me3-Ph 981 Me CH(Et)CH2OH 2,4,6-Me3-Ph 982 Me CH(Et)CH2OMe 2,4,6-Me3-Ph 983 Me CONMe2 2,4,6-Me3-Ph 984 Me COCH3 2,4,6-Me3-Ph 985 Me CH(OH)CH3 2,4,6-Me3-Ph 986 Me C(OH)Ph-3-pyridyl 2,4,6-Me3-Ph 987 Me Ph 2,4,6-Me3-Ph 968 Me 2-Ph-Ph 2,4,6-Me3-Ph 989 Me 3-pentyl 2,4, 6-Me3-Ph 990 Me cyclobutyl 2,4,6-Me3-Ph 991 Me 3-pyridyl 2,4,6-Me3-Ph 992 Me CH(Et)CH2CONMe2 2,4,6-Me3-Ph 993 Me CH(Et)CH2CH2NMe2 2,4,6-Me3-Ph 994 Me NHCH(CH2OMe)2 2,4-Me2-Ph 995 Me N(CH2CH2OMe)2 2,4-Me2-Ph 996 Me NHcH(Et)cH2oMe 2,4-Me2-Ph 997 Me NH-3-pentyl 2,4-Me2-Ph 998 Me NEt2 2,4-Me2-Ph 999 Me N(CH2CN)2 2,4-Me2-Ph 1000 Me NHCH(Me)CH2OMe 2,4-Me2-Ph 1001 Me OCH(Et)CH2OMe 2,4-Me2-Ph 1002 Me NPr-c-C3H5 2,4-Me2-Ph 1003 Me NHCH(Me)CH2NMe2 2,4-Me2-Ph 1004 Me N(c-C3HS)CH2CH2CN 2,4-Me2-Ph 1005 Me N(Pr)CH2CH2CN 2,4-Me2-Ph 1006 Me N(Bu)CH2CH2CN 2,4-Me2-Ph 1007 Me NHCHPr2 2,4-Me2-Ph 1008 Me NEtBu 2,4-Me2-Ph 1009 Me NPr(CH2-c-C3H5) 2,4-Me2-Ph 1010 Me NH-3-heptyl 2,4-Me2-Ph 1011 Me NEt2 2,4-Me2-Ph 1012 Me NHCH(CH2OEt)2 2,4-Me2-Ph 1013 Me NH-3-pentyl 2,4-Me2-Ph 1014 Me NMePh 2,4-Me2-Ph 1015 Me NPr2 2, 4-Me2-Ph 1016 Me NH-3-hexyl 2,4-Me2-Ph 1017 Me morpholino 2,4-Me2-Ph 1018 Me N(CH2Ph)CH2CH2OMe 2,4-Me2-Ph 1019 Me NHCH(CH2Ph)CH2OMe 2,4-Me2-Ph 1020 Me NH-4-tetrahydropyranyl 2,4-Me2-Ph 1021 Me NH-cyclopentyl 2,4-Me2-Ph 1022 Me NHCH(CH2OMe)2 2-Me-4-MeO-Ph 1023 Me N(CH2CH2OMe)2 2-Me-4-MeO-Ph 1024 Me NHCH(Et)CH2OMe 2-Me-4-MeO-Ph 1025 Me N(Pr)CH2CH2CN 2-Me-4-MeO-Ph 1026 Me OCH(Et)CH2OMe 2-Me-4-MeO-Ph 1027 Me NHCH(CH2OMe)2 2-Br-4-MeO-Ph 1028 Me N(CH2CH2OMe)2 2-Br-4-MeO-Ph 1029 Me NHCH(Et)CH2OMe 2-Br-4-MeO-Ph 1030 Me N(Pr)CH2CH2CN 2-Br-4-MeO-Ph 1031 Me OCH(Et)CH20Me 2-Br-4-MeO-Ph 1032 Me NHCH(CH2OMe)2 2-Me-4-NMe2-Ph 1033 Me N(CH2CH2OMe)2 2-Me-4-NMe2-Ph 1034 Me NHCH(Et)CH2OMe 2-Me-4-NMe2-Ph 1035 Me N(Pr)CH2CH2CN 2-Me-4-NMe2-Ph 1036 Me OCH(Et) CH2OMe 2-Me-4-NMe2-Ph 1037 Me NHCH(CH2OMeX2 2-Br-4-NMe2-Ph 1038 Me N(CH2CH2OMe12 2-Br-4-NMe2-Ph 1039 Me NHCH(Et > CH2OMe 2-Br-4-NMe2-Ph 1040 Me N(Pr)CH2CH2CN 2-Br-4-NMe2-Ph 1041 Me OCH(Et)CH2OMe 2-Br-4-NMe2-Ph 1042 Me NHCH(CH2OMe)2 2-Br-4-i-Pr-Ph 1043 Me N(CH2CH2OMe)2 2-Br-4-i-Pr-Ph 1044 Me NHCH(Et)CH2OMe 2-Br-4-i-Pr-Ph 1045 Me N(Pr)CH2CH2CN 2-Br-4-i-Pr-Ph 1046 Me OCH(Et)CH2OMe 2-Br-4-i-Pr-Ph 1047 Me NHCH(CH2OMe)2 2-Br-4-Me-Ph 1048 Me N(CH2CH2OMe)2 2-Br-4-Me-Ph 1049 Me NHCH(Et)CH2OMe 2-Br-4-Me-Ph 1050 Me N(Pr)CH2CH2CN 2-Br-4-Me-Ph 1051 Me OCH(Et)CH2OMe 2-Br-4-Me-Ph 1052 Me NHCH(CH2OMe)2 2-Me-4-Br-Ph 1053 Me N(CH2cH2OMe)2 2-Me-4-Br-Ph 1054 Me NHCH(Et)CH2OMe 2-Me-4-Br-Ph 1055 Me N(Pr) CH2CH2CN 2-Me-4-Br-Ph 1056 Me OCH(Et)CH2OMe 2-Me-4-Br-Ph 1057 Me NHCH(cH2OMe)2 2-C1-4,6-Me2-Ph 1058 Me N(CH2cH2OMe)2 2-Cl-4,6-Me2-Ph 1059 Me NHCH(CH2OMe)2 4-Br-2,6-(Me)2-Ph 1060 Me N(CH2cH2OMe)2 4-Br-2,6-(Me)2-Ph 1061 Me NHCH(CH2OMe)2 4-i-Pr-2-SMe-Ph 1062 Me N(CH2CH2OMe)2 4-i-Pr-2-SMe-Ph 1063 Me NHCH(CH2OMe)2 2-Br-4-CF3-Ph 1064 Me N(CH2cH2OMe)2 2-Br-4-CF3-Ph 1065 Me NHCH(CH2OMe)2 2-Br-4,6-(MeO)2-Ph 1066 Me N(CH2cH2OMe)2 2-Br-4,6-(MeO)2-Ph 1067 Me NHCH(CH2OMe)2 2-Cl-4,6-(MeO)2-Ph 1068 Me N(CH2CH2OMe)2 2-C1-4,6-(MeO)2-Ph 1069 Me NHCH(CH2OMe)2 2,6-(Me)2-4-SMe-Ph 1070 Me N(CH2cH2OMe)2 2,6-(Me)2-4-SMe-Ph 1071 Me NHCH(CH2OMe)2 4-(COMe) -2-Br-Ph 1072 Me N(CH2CH2OMe)2 4-(COMe)-2-Br-Ph 1073 Me NHCH(CH2OMe)2 2,4,6-Me3-pyrid-3-yl 1074 Me N(CH2CH2OMe)2 2,4,6-Me3-pyrid-3-yl 1075 Me NHCH(CH2OMe)2 2,4-(Br)2-Ph 1076 Me N(CH2CH2OMe)2 2,4-(Br)2-Ph 1077 Me NHCH(CH2OMe)2 4-i-Pr-2-SMe-Ph 1078 Me N(CH2cH2OMe)2 4-i-Pr-2-SMe-Ph 1079 Me NHCH(cH2OMe)2 4-i-Pr-2-SO2Me-Ph 1080 Me N(CH2CH2OMe)2 4-i-Pr-2-S02Me-Ph 1081 Me NHCH(cH2OMe)2 2,6-(Me)2-4-SMe-Ph 1082 Me N(CH2cH2OMe)2 2,6-(Me)2-4-SMe-Ph 1083 Me NHCH(CH2OMe)2 2,6-(Me)2-4-SO2Me-Pb 1084 Me N(CH2CH2OMe)2 2,6-(Me)2-4-SO2Me-Pb 1085 Me NHCH(CH2OMe)2 2-I-4-i-Pr-Ph 1086 Me N(CH2CH2OMe)2 2-I-4-i-Pr-Ph 1087 Me NHCH(CH2OMe)2 2-Br-4-N(Me) 2-6-MeO-Ph 1088 Me N(CH2cH2OMe)2 2-Br-4-N(Me)2-6-MeO-Ph 1089 Me NEt2 2-Br-4-MeO-Ph 1090 Me NH-3-pentyl 2-Br-4-MeO-Ph 1091 Me NHCH(CH2OMe)2 2-CN-4-Me-Ph 1092 Me N(c-C3H5)CH2CH2CN 2,4,6-Me3-Ph 1093 Me NHCH(CH2CH2OMe)CH2OMe 2-Me-4-Br-Ph 1094 Me NHCH(CH2OMe)2 2,5-Me2-4-MeO-Ph 1095 Me N(CH2cH2OMe)2 2,5-Me2-4-MeO-Ph 1096 Me NH-3-pentyl 2,5-Me2-4-MeO-Ph 1097 Me NEt2 2,5-Me2-4-MeO-Ph 1098 Me NHCH(CH2oMe)2 2-Cl-4-MePh 1099 Me NCH(Et)CH2OMe 2-C1-4-MePh 1100 Me N(CH2cH2OMe)2 2-C1-4-MePh 1101 Me (S)-NHCH(CH2CH2OMeXCH2OMe 2-C1-4-MePh 1102 Me N(c-C3Hs)CH2cH2cN 2,5-Me2-4-MeOPh 1103 Me NEt2 2-Me-4-MeOPh 1104 Me OEt 2-Me-4-MeOPh 1105 Me (S) -NHCH(CH2CH2OMe)CH2OMe 2-Me-4-MeOPh 1106 Me N(c-C3H5)CH2CH2CN 2-Me-4-MeOPh 1107 Me NHCH(CH2CH2OEt)2 2-Me-4-MeOPh 1108 Me N(c-C3H5)CH2CH2CN 2,4-C12-Ph 1109 Me NEt2 2-Me-4-ClPh 1110 Me NH-3-pentyl 2-Me-4-ClPh 1111 Me N(CH2CH2OMe)2 2-Me-4-ClPh 1112 Me NHCH(CH2OMe)2 2-Me-4-ClPh 1113 Me NEt2 2-Me-4-ClPh 1114 Me NEt2 2-C1-4-MePh 1115 Me NH-3-pentyl 2-C1-4-MePh 1116 Me NHCH(CH2OMe)2 2-C1-4-MeOPh 1117 Me N(CH2CH2OMe)2 2-C1-4-MeOPh 1118 Me NHCH(Et)CH2OMe 2-C1-4-MeOPh 1119 Me N(c-Pr)CH2CH2CN 2-C1-4-MeOPh 1120 Me NEt2 2-C1-4-MeOPh 1121 Me NH-3-pentyl 2-C1-4-MeOPh 1123 Me NHCH(Et)CH2CH2OMe 2-C1-4-MeOPh 1124 Me NHCH(Me)CH2CH2OMe 2-C1-4-MeOPh 1125 Me NHCH(Et)CH2CH2OMe 2-Br-4-MeOPh 1126 Me NHCH(Me)CH2CH2OMe 2-Br-4-MeOPh 1127 Me NHCH(Et) CH2CH2OMe 2-Me-4-MeOPh 1128 Me NHCH(Me)CH2CH2OMe 2-Me-4-MeOPh 1129 Me NHCH(CH2OMe)2 2-Cl-4,5-(MeO)2Ph 1130 Me N(CH2CH2OMe)2 2-Cl-4,5-(MeO)2Ph 1131 Me NHCH(Et)CH2OMe 2-Cl-4,5-(MeO)2Ph 1132 Me N(c-Pr)CH2CH2CN 2-Cl-4,5-(MeO)2Ph 1133 Me NEt2 2-C1-4,5-(MeO)2Ph 1134 Me NH-3-pentyl 2-C1-4,5-(MeO)2Ph 1135 Me NHCH(Et)CH2CH2OMe 2-Cl-4,5-(MeO)2Ph 1136 Me NHCH(Me)CH2CH2OMe 2-Cl-4,5-(MeO)2Ph 1137 Me NHCH(CH2OMe)2 2-Br-4,5-(MeO)2Ph 1138 Me N(CH2cH2OMe)2 2-Br-4,5-(MeO)2Ph 1139 Me NHCH(Et)CH2OMe 2-Br-4,5-(MeO)2Ph 1140 Me N(c-Pr)CH2CH2CN 2-Br-4,5-(MeO)2Ph 1141 Me NEt2 2-Br-4,5-(MeO)2Ph 1142 Me NH-3-pentyl 2-Br-4,5-(MeO)2Pb 1143 Me NHCH(cH2OMe)2 2-C1-4,6-(MeO) 2Ph 1144 Me N(CH2CH2OMe)2 2-Cl-4,6-(MeO)2Ph 1145 Me NEt2 2-Cl-4,6-(MeO)2Ph 1146 Me NH-3-pentyl 2-C1-4,6-(MeO)2Ph 1147 Me NHCH(CH2OMe)2 2-Me-4,6-(MeO)2Ph 1148 Me N(CH2CH2OMe)2 2-Me-4,6-(MeO)2Ph 1149 Me NHCH(Et)CH2OMe 2-Me-4,6-(MeO)2Ph 1150 Me NEt2 2-Me-4,6-(MeO)2Ph 1151 Me NH-3-pentyl 2-Me-4,6-(MeO)2Ph 1152 Me NHCH(Et)CH2CH2OMe 2-Me-4-MeOPh 1153 Me NHCH(Me)CH2CH2OMe 2-Me-4-MeOPh 1154 Me NHCH(CH2OMe)2 2-Me0-4-MePh 1155 Me N(CH2CH2OMe)2 2-Me0-4-MePh 1156 Me NHCH(Et)CH2OMe 2-MeO-4-MePh 1157 Me N(c-Pr)CH2CH2CN 2-Me0-4-MePh 1158 Me NEt2 2-Me0-4-MePh 1159 Me NH-3-pentyl 2-Me0-4-MePh 1160 Me NHCH(Et)cH2CH2OMe 2-Me0-4-MePh 1161 Me NHCH(Me)cH2cH2oMe 2-MeO-4-MePh 1162 Me NHCH(CH2OMe)2 2-MeO-4-MePh 1163 Me N(CH2CH2OMe)2 2-MeO-4-MePh 1164 Me NHCH(Et)CH2OMe 2-MeO-4-MePh 1165 Me N(c-Pr) CH2CH2CN 2-MeO-4-MePh 1166 Me NEt2 2-MeO-4-MePh 1167 Me NH-3-pentyl 2-MeO-4-MePh 1168 Me NHCH(cH2OMe)2 2-MeO-4-ClPh 1169 Me N(CH2cH2OMe)2 2-Me0-4-C1Ph 1170 Me NHCH(Et)CH2OMe 2-Me0-4-C1Ph 1171 Me NEt2 2-Me0-4-C1Ph 1172 Me NH-3-pentyl 2-MeO-4-ClPh futility 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 XhoI + XbaI and cloned into the XhoI + XbaI 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 zM 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 108 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 hORFRl receptors is homogenized in 10 ml of ice cold tissue buffer ( 50 mM HEPES buffer pH 7.0, containing 10 mM MgC12, 2 mM EGTAr 1 Ag/l aprotinin, 1 pgZml leupeptin and 1 pg/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 40,000x g for 12 min, the pellet is resuspended to a protein concentration of 360 Ag/ml to be used in the assay. Binding assays are performed in 96 well plates; each well having a 300 A1 capacity. To each well is added 50 41 of test drug dilutions (final concentration of drugs range from 10-10 - 10-5 M), 100 41 of 125Iovine-CRF (1251-o-CRF) (final concentration 150 pM) and 150 A1 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 125I-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. Inhibition of CRF-Stlmulated Adenylate Cvclase Activitv Inhibition of CRF-stimulated adenylate cyclase activity can be performed as described by G. Battaglia et al. Synapse 1:572 (1987) . Briefly, as says are carried out at 370 C for 10 min in 200 ml of buffer containing 100 mM Tris-HCl (pH 7.4 at 370 C), 10 mM MgC12, 0.4 mM EGTA, 0.18 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 10-6m) and 0.8 mg original wet weight tissue (approximately 40-60 mg protein). Reactions are initiated by the addition of 1 mM ATP/32P]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 ijl of [3H]cAMP (approximately 40,000 dpm) is added to each tube prior to separation. The separation of [32P]cAMP from [32P]ATP is performed by sequential elution over Dowex and alumina columns. In vivo Biological Assav The in vivo activity of the compounds of the present invention can be assessed using any one of the biological as says available and accepted within the art. Illustrative of these tests inclu 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. 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 disorders1 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 agents1 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, methylor 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. Although the present invention has been described and exemplified in terms of certain preferred embodiments, other embodiments will be apparent to those skilled in the art. The invention is, therefore, not limited to the particular embodiments described and exemplified, but is capable of modification or variation without departing from the spirit of the invention, the full scope of which is delineated by the appended claims.

Claims: CLAIMS WHAT IS CLAIMED IS: 1. A method of treating affective disorder, anxiety, depression, headache, irritable bowel syndrome, post-traumatic stress disorder, supranuclear palsy, immune suppression, Alzheimer's disease, gastrointestinal diseases, anorexia nervosa or other feeding disorder, drug addiction, drug or alcohol withdrawal symptoms1 inflammatory diseases, cardiovascular or heart-related diseases, fertility problems, human immunodeficiency virus infections, hemorrhagic stress, obesity, infertility, head and spinal cord traumas, epilepsy, stroke, ulcers, amyotrophic lateral sclerosis, hypoglycemia or a disorder the treatment of which can be effected or facilitated by antagonizing CRF, including but not limited to disorders induced or facilitated by CRF, in mammals comprising administering to the mammal a therapeutically effective amount of a compound of Formulae (1) or (2): EMI169.1 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof, wherein: A is N or CR; Z is N or CR2; Ar is selected from phenyl, naphthyl, pyridyl, pyrimidinyl, triazinyl, furanyl, thienyl, benzothienyl, benzofuranyl, 2,3 dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, indanyl, 1,2-benzopyranyl, 3,4-dihydro-1,2 benzopyranyl, tetralinyl, each Ar optionally substituted with 1 to 5 R4 groups and each Ar is attached to an unsaturated carbon atom; R is independently selected at each occurrence from H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, halo, CN, C1-C4 haloalkyl; R1 is independently selected at each occurrence from H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, halo1 CN, C1-C4 haloalkyl, C1-C12 hydroxyalkyl, C2-C12 alkoxyalkyl, C2-C10 cyanoalkyl, C3-C6 cycloalkyl, C4-C10 cycloalkylalkyl, NR9R10, Cl- C4 alkyl-NR9R10, NR9CoR10, OR11, SH or S(O)nR12; R2 is selected from H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl, C4-C10 cycloalkylalkyl, C1-C4 hydroxyalkyl, halo, CN, -NR6R7, NR9CoR10, -NR6S(O)nR7, S(O)nNR6R7, 01- C4 haloalkyl, -OR7, SH or -S(O)nR12; R3 is selected from: -H, OR7, SH, S(O)nR13, COR7, CO2R7, OC(O)R13, NR8COR7, N(COR7)2, NR8CONR6R7, NR8CO2R13, NR6R7, NR6aR7a, N(OR7)R6, CONR6R7, aryl1 heteroaryl and heterocyclyl, or -C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-Cg cycloalkyl, C5-Cg cycloalkenyl, 04- C12 cycloalkylalkyl or C6-C10 cycloalkenylalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo1 C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO@R13 NR16R15, CONR16R15, aryl, heteroaryl and heterocyclyl; R4 is independently selected at each occurrence from: C1-C10 alkyl, C2-C10 alkenyl, C2-Clo alkynyl, C3-C6 cycloalkyl, C4-C12 cycloalkylalkyl, N02, halo, CN, C1-C4 haloalkyl, NR6R7, NR8CoR7, NR8CO2R7, COR7, OR7, CONR6R7, CO(NOR9)R7, CO2R7, or S(O)nR7, where each such C1-C10 alkyl, 02- C10 alkenyl, C2-C10 alkynyl, C3-C6 cycloalkyl and C4-C12 cycloalkylalkyl are optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, NO2, halo, CN, NR6R7, NR8CoR7, NR8CO2R7, COR7 OR7, CONR6R7, CO2R7, CO(NOR9)R7, or S(O)nR7; R6 and R7, R6a and R7a are independently selected at each occurrence from: -H, -C1-C10 alkyl, C3-C10 alkenyl, C3-ClO alkynyl, C1-C10 haloalkyl with 1-10 halogens, C2-Cg alkoxyalkyl, C3-C6 cycloalkyl, 04- C12 cycloalkylalkyl, C5-C10 cycloalkenyl, or C6-C14 cycloalkenylalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, 03- C6 cycloalkyl, halo1 C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl, -aryl, aryl(C1-C4 alkyl), heteroaryl, heteroaryl(C1-C4 alkyl), heterocyclyl or heterocyclyl(C1-C4 alkyl); alternatively, NR6R7 andNR6aR7a are independently piperidine, pyrrolidine, piperazine, Nmethylpiperazine, morpholine or thiomorpholine, each optionally substituted with 1-3 C1-C4 alkyl groups; R8 is independently selected at each occurrence from H or C1-C4 alkyl; R9 and R10 are independently selected at each occurrence from H, C1-C4 alkyl, or C3-C6 cycloalkyl; K11 is selected from H, C1-C4 alkyl, C1-C4 haloalkyl, or C3-C6 cycloalkyl; R12 is C1-C4 alkyl or C1-C4 haloalkyl; R13 is selected from C1-C4 alkyl, C1-C4 haloalkyl, C2-Cg alkoxyalkyl, C3-C6 cycloalkyl, 04- C12 cycloalkylalkyl, aryl, aryl(C1-C4 alkyl)-, heteroaryl or heteroaryl(C1-C4 alkyl)-; R14 is selected from C1-C10 alkyl, C3-C10 alkenyl, 03- C10 alkynyl, C3-C8 cycloalkyl, or C4 C12 cycloalkylalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, 03- C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR15, COR15, CO2R15, OC(O)R15, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R15, NR16R151 CONR16R15, and C1-C6 alkylthio, C1-C6 alkylsulfinyl and C1-C6 alkylsulfonyl; R15 and R16 are independently selected at each occurrence from H, C1-C6 alkyl, C3-C10 cycloalkyl, C4-C16 cycloalkylalkyl, except that for S(O)nR15, R15 cannot be H; aryl is phenyl or naphthyl, each optionally substituted with 1 to 5 substituents independently selected at each occurrence from C1-C6 alkyl, 03- C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR15, COR15, CO2R15, OC(O)R15, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R15, NR16R15, and CONR16R15; heteroaryl is pyridyl, pyrimidinyl, triazinyl, furanyl, pyranyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, isoxazolyl, pyrazolyl, 2,3 dihydrobenzothienyl or 2, 3-dihydrobenzofuranyl, each being optionally substituted with 1 to 5 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR15, -00K15, C02R15, O0(O)R15, NR8CoR15, N(COR15)2, NR8CONR16R15, NR8CO2R15, NR16R15, and CONR16R15; heterocyclyl is saturated or partially saturated heteroaryl, optionally substituted with 1 to 5 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR15, COR15, CO2R15, OC(O)R15, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R15, NR15R16, and CONR16R15; n is independently at each occurrence 0, 1 or 2, 2. A method of claim 1 wherein, in the compound of Formulae (1) or (2), Ar is phenyl, pyridyl or 2,3dihydrobenzofuranyl, each optionally substituted with 1 to 4 R4 substituents. 3. A method of claim 1 wherein, in the compound of Formulae (1) or (2), A is N, Z is CR2, Ar is 2,4dichlorophenyl, 2,4-dimethylphenyl or 2,4,6trimethylphenyl, R1 and R2 are CH3, and R3 is NR6aR7a. 4. A compound of Formulae (1) or (2): EMI175.1 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof 1 and pharmaceutically acceptable salt or pro-drug forms thereof wherein: A is N or CR; Z is N or CR2; Ar is selected from phenyl, naphthyl, pyridyl, pyrimidinyl, triazinyl, furanyl, thienyl, benzothienyl, benzofuranyl, 2,3 dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, indanyl, 1,2-benzopyranyl, 3,4-didro-1,2 benzopyranyl, tetralinyl, each Ar optionally substituted with 1 to 5 R4 groups and each Ar is attached to an unsaturated carbon atom; R is independently selected at each occurrence from H, C1-Cq alkyl, C2-Cq alkenyl, C2-Cq alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, halo, CN, C1-C4 haloalkyl; R1 is independently selected at each occurrence from H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, halo, CN, C1-C4 haloalkyl, C1-C12 hydroxyalkyl, C2-Cl2 alkoxyalkyl, C2-C10 cyanoalkyl, C3-C6 cycloalkyl, C4-C10 cycloalkylalkyl, NR9R10, Cl- C4 alkyl-NR9R10, NR9COR10, OR11, SH or S(O)nR12; R2 is selected from H, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl, C4-C10 cycloalkylalkyl, C1-C4 hydroxyalkyl, halo, CN, -NR6R7, NR9COR10, -NR6S(O)nR7, S(O)nNR6R7, C1 C4 haloalkyl, -OR7, SH or -S(O)nR12; R3 is selected from: -H, OR7, SH, S(O)nR13, COR7, CO2R7, OC(O)R13, NR8COR7, N(COR7)2, NR8CONR6R7, NR8C02R131 NR6R71 NR6aR7a, N(0R7)R6, CoNR6R7, aryl, heteroaryl and heterocyclyl, or -C1-C10 alkyl, C2-C1Í alkenyl, C2-C10 alkynyl, C3-Cg cycloalkyl, C5-Cg cycloalkenyl, C4- C12 cycloalkylalkyl or C6-C10 cycloalkenylalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl and heterocyclyl; R4 is independently selected at each occurrence from: C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C6 cycloalkyl, C4-C12 cycloalkylalkyl, N02, halo, CN, C1-C4 haloalkyl, NR6R7, NR8CoR7, NR8CO2R7, COR7, OR7, CONR6R7, CO(NOR9)R7, CO2R7, or S(O)nR7, where each such C1-C10 alkyl1 02- C10 alkenyl, C2-C10 alkynyl, C3-C6 cycloalkyl and C4-C12 cycloalkylalkyl are optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C4 alkyl, N02, halo, CN, NR6R7, NR8COR7, NR8CO2R7, COR7 OR7, CONR6R7, CO2R7, CO(NOR9)R7, or S(O)nR7; R6 and R7, R6a and R7a are independently selected at each occurrence from: -H, -C1-C10 alkyl, C3-C10 alkenyl, C3-C10 alkynyl, C1-C10 haloalkyl with 1-10 halogens, C2-Cg alkoxyalkyl, C3-C6 cycloalkyl, 04- C12 cycloalkylalkyl, C5-C10 cycloalkenyl, or C6-C14 cycloalkenylalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, 03- C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl, -aryl, aryl(C1-CA alkyl), heteroaryl, heteroaryl(C1-C4 alkyl), heterocyclyl or heterocyclyl(C1-C4 alkyl), alternatively, NR6R7 and NR6aR7a are independently piperidine, pyrrolidine, piperazine, Nmethylpiperazine, morpholine or thiomorpholine, each optionally substituted with 1-3 C1-C4 alkyl groups; R8 is independently selected at each occurrence from H or C1-C4 alkyl; R9 and R10 are independently selected at each occurrence from H, C1-C4 alkyl, or C3-C6 cycloalkyl; K11 is selected from H, C1-C4 alkyl, C1-C4 haloalkyl, or C3-C6 cycloalkyl; R12 is C1-C4 alkyl or C1-C4 haloalkyl; R13 is selected from C1-C4 alkyl1 C1-C4 haloalkyl, C2-Cg alkoxyalkyl, C3-C6 cycloalkyl, 04- C12 cycloalkylalkyl, aryl, aryl(C1-C4 alkyl)-, heteroaryl or heteroaryl(C1-C4 alkyl)-; R14 is selected from C1-C10 alkyl, C3-C10 alkenyl, 03- C10 alkynyl, C3-Cg cycloalkyl, or 04- C12 cycloalkylalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, 03- C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano1 OR15, SH, S(O)nR15, COR15, CO2R15, OC(O)R15, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R15, NR16R15, CONR16R15, and C1-C6 alkylthio, C1-C6 alkylsulfinyl and C1-C6 alkylsulfonyl; R15 and R16 are independently selected at each occurrence from H, C1-C6 alkyl, C3-C10 cycloalkyl, C4-C16 cycloalkylalkyl, except that for S(O)nR15, R15 cannot be H; aryl is phenyl or naphthyl, each optionally substituted with 1 to 5 substituents independently selected at each occurrence from C1-C6 alkyl, 03- C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR15, COR15, CO2R15, OC(O)R15, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R15, NR16R151 and CONR16R15; heteroaryl is pyridyl, pyrimidinyl, triazinyl, furanyl, pyranyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, isoxazolyl, pyrazolyl, 2,3 dihydrobenzothienyl or 2, 3-dihydrobenzofuranyl, each being optionally substituted with 1 to 5 substituents independently selected at each occurrence from C1-C6 alkyl1 C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR15, -COR15, CO2R15, OC(O)R15, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R15, NR16R15, and CONR16R15; heterocyclyl is saturated or partially saturated heteroaryl, optionally substituted with 1 to 5 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR15, COR15, CO2R15, OC(O)R15, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R15, NR15R16, and CONR16R15 n is independently at each occurrence 0, 1 or 2, with the provisos that: (1) when A is N, Z is CR2, R2 is H, R3 is -OR7 or -OCOR13, and R7 is H, then R1 is not H, OH or SH; (2) when A is N, Z is CR2, R1 is CH3 or C2Hs, R2 is H, and R3 is OH, H, CH3, C2Hs, C6Hs, n-C3H7, i-C3H7, SH, SCH3, NHC4H9, or N(C2H5)2, then Ar is not phenyl or m-CH3-phenyl; (3) when A is N, Z is CR2, R2 is H, and Ar is pyridyl, pyrimidinyl or pyrazinyl, and R3 is NR6aR7a, then R6a and R7a are not H or alkyl; (4) when A is N, Z is CR21 and R2 is SO2NR6R7, then R3 is not OH or SH; (5) when A is CR and Z is CR2, then R2 is not-NR6S02R7 or -SO2NR6R7; (6) when A is N, Z is CR2 and R2 is -NR6So2R7 or -SO2NR6R7, then R3 is not OH or SH; (7) when A is N, Z is CR2, R1 is methyl or ethyl, R2 is H, and R is H, OH, CH3, C2H5, C6H5, n-C3H7, iso-C3H7, SH, SCH3, NH(n-C4H9), or N(C2H5)2, then Ar is not unsubstituted phenyl or m-methylphenyl; (8) when A is CR, Z is CRê, R2 is H, phenyl or alkyl, R3 is NR8COR7 and Ar is phenyl or phenyl substituted with phenylthio, then R7 is not aryl, aryl(C1-C4 alkyl), heteroaryl, heteroaryl(C1-C4 alkyl), heterocyclyl or heterocycly(C1-C4 alkyl); (9) when A is CR, Z is CRê, R2 is H or alkyl, Ar is phenyl, and R is SR13 or NR6aR7a, then R13 is not aryl or heteroaryl and R6a and R7a are not H or aryl; or (10) when A is CH, Z is CRê, R1 is OR11, R2 is H, R3 is OR7, and R7 and R11 are both H, then Ar is not phenyl, p-Br-phenyl, p-Cl-phenyl, p-NHCOCH3 phenyl, p-CH3-phenyl, pyridyl or naphthyl; (11) when A is CH, Z is CR2, R2 is H, Ar is unsubstituted phenyl, and R3 is CH3, C2H5, CF3 or C6H4F, then R1 is not CF3 or C2F5; (12) when A is CR, R is H, Z is CRê, R2 is OH, and R1 and R3 are H, then Ar is not phenyl; (13) when A is CR, R is H, Z is CR2, R2 is OH or NH2, R1 and R3 are CH3, then Ar is not 4 phenyl-3-cyano-2-aminopyrid-2-yl. 5. A compound of claim 4 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof with the additional provisos that (1) when A is N, R1 is H, C1-C4 alkyl, halo, CN, C1-C12 hydroxyalkyl, C1-C4 alkoxyalkyl or S02(C1-C4 alkyl), R3 is NR6aR7a and R6a is unsubstituted C1-C4 alkyl, then R7a is not phenyl, naphthyl, thienyl, benzothienyl, pyridyl, quinolyl, pyrazinyl, furanyl, benzofuranyl, benzothiazolyl, indolyl or C3-C6 cycloalkyl; and (2) A is N, R1 is H, C1-C4 alkyl, halo1 CN, C1-C12 hydroxyalkyl, C1-C4 alkoxyalkyl or SO2(C1-C4 alkyl)1 R3 is NR6aR7a and R7a is unsubstituted C1-C4 alkyl, then R6a is not phenyl, naphthyl, thienyl, benzothienyl, pyridyl, quinolyl, pyrazinyl, furanyl, benzofuranyl, benzothiazolyl, indolyl or C3-C6 cycloalkyl. 6. A compound of claim 4 and isomers thereof, stereoisomeric forms thereof1 or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein Ar is phenyl, pyridyl or 2,3-dihydrobenzofuranyl, each optionally substituted with 1 to 4 R4 substituents. 7. A compound of claim 6 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein A is N, Z is CR2, Ar is 2,4-dichlorophenyl, 2,4dimethylphenyl or 2,4,6-trimethylphenyl, R1 and R2 are CH3, and R3 is NR6aR7a. 8. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 4. 9. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 6. 10. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 7. 11. A compound of claim 4 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein A is N. 12. A compound of Formula (2) of claim 11 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof. 13. A compound of claim 12 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein Ar is phenyl, pyridyl or 2,3-dihydrobenzofuranyl and each Ar is optionally substituted with 1 to 4 R4 substituents. 14. A compound of claim 12 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R3 is NR6aR7a or OR7. 15. A compound of claim 12 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein Ar is phenyl, pyridyl or 2,3-dihydrobenzofuranyl, and each Ar is optionally substituted with 1 to 4 R4 substituents, and R3 is NR6aR7a or OR7. 16. A compound of Formula (1) of claim 11 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof 1 and pharmaceutically acceptable salt or pro-drug forms thereof wherein Z is CR2. 17. A compound of claim 16 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein Ar is phenyl, pyridyl or 2,3-dihydrobenzofuranyl and each Ar is optionally substituted with 1 to 4 R4 substituents. 18. A compound of claim 16 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R3 is NR6aR7a or OR7. 19. A compound of claim 18 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R6a is independently selected from: -H, -C1-C10 alkyl, C3-C10 alkenyl, C3-C10 alkynyl, C1-C10 haloalkyl with 1-10 halogens, C2-Cg alkoxyalkyl, C3-C6 cycloalkyl, 04- C12 cycloalkylalkyl, C5-C10 cycloalkenyl, or C6-C14 cycloalkenylalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, 03- C6 cycloalkyl, halo1 C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, C02R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl, -aryl, aryl(Cl-C4 alkyl)-, heteroaryl, heteroaryl(C1-C4 alkyl)-, heterocyclyl or heterocyclyl(C1-C4 alkyl)-; and R7a is independently selected at each occurrence from: -H, -C5-C10 alkyl, C3-C10 alkenyl, C3-C10 alkynyl, C1-C10 haloalkyl with 1-10 halogens1 C2-Cg alkoxyalkyl, C3-C6 cycloalkyl, 04- C12 cycloalkylalkyl, C5-C10 cycloalkenyl, or C6-C14 cycloalkenylalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, 03- C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl, -aryl, aryl(C1-C4 alkyl), heteroaryl, heteroaryl(C1-C4 alkyl)1 heterocyclyl or heterocyclyl(C1-C4 alkyl); alternatively, NR6R7 and NR6aR7a are independently piperidine, pyrrolidine, piperazine, Nmethylpiperazine, morpholine or thiomorpholine, each optionally substituted with 1-3 C1-C4 alkyl groups. 20. A compound of claim 18 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R6a and R7a are identical and are selected from: -C1-C4 alkyl or C3-C6 cycloalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, -COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R13, NRl6Rl5 CONR16R15, aryl, heteroaryl or heterocyclyl, and -aryl or heteroaryl. 21. A compound of claim 18 and isomers thereof1 stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R6a is selected from: -H, -C1-C10 alkyl, C3-C10 alkenyl, C3-C10 alkynyl, Cl-C 10 haloalkyl with 1-10 halogens, C2-Cg alkoxyalkyl, C3-C6 cycloalkyl, 04- C12 cycloalkylalkyl, C5-C10 cycloalkenyl, or C6-C14 cycloalkenylalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, 03- C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl, -aryl, aryl(C1-C4 alkyl), heteroaryl, heteroaryl(C1-C4 alkyl), heterocyclyl or heterocyclyl(C1-C4 alkyl); R7a is selected from: -C1-C4 alkyl and each such C1-C4 alkyl is substituted with 1-3 substituents independently selected at each occurrence from Cl-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CoNR16R15, NR8C02R13, NR16R15, CoNR16R15, aryl, heteroaryl or heterocyclyl. 22. A compound of claim 18 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutic-ally acceptable salt or pro-drug forms thereof wherein one of R6a and R7a is selected from: -C3-C6 cycloalkyl, each such C3-C6 cycloalkyl optionally substituted with 1-3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl, -aryl, -heteroaryl or -heterocyclyl, and the other of R6a and R7a is unsubstituted C1-C4 alkyl. 23. A compound of claim 18 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R6a and R7a are independently H or C1-C10 alkyl, each such C1-C10 alkyl optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR131 COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, R8CONR16R15, NR8Co2Rl3 NR16R15, coNR16R15 aryl heteroaryl or heterocyclyl. 24. A compound of claim 16 and isomers thereof1 stereoisomeric forms thereof 1 or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein Ar is phenyl, pyridyl or 2,3-dihydrobenzofuranyl, and each Ar is optionally substituted with 1 to 4 R4 substituents, and R3 is NR6aR7a or OR7. 25. A compound of claim 24 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R6a is independently selected from: -H, -C1-C10 alkyl, C3-C10 alkenyl, C3-C10 alkynyl, C1-C10 haloalkyl with 1-10 halogens, C2-Cg alkoxyalkyl, C3-C6 cycloalkyl, 04- C12 cycloalkylalkyl, C5-C10 cycloalkenyl, or C6-C14 cycloalkenylalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, 03- C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, oC(o)R13, NR8CoR15, N(COR15)2 NR8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl, -aryl, aryl(Cl-C4 alkyl)-, heteroaryl, heteroaryl(C1-C4 alkyl), heterocyclyl or heterocyclyl(C1-C4 alkyl); R7a is independently selected at each occurrence from: -H, -C5-C10 alkyl1 C3-C1o alkenyl, C3-C10 alkynyl, C1-C10 haloalkyl with 1-10 halogens, C2-Cg alkoxyalkyl, C3-C6 cycloalkyl, 04- C12 cycloalkylalkyl, C5-C10 cycloalkenyl, or C6-C14 cycloalkenylalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, 03- C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO alternatively, NR6R7 and NR6aR7a are independently piperidine, pyrrolidine, piperazine, Nmethylpiperazine, morpholine or thiomorpholine, each optionally substituted with 1-3 C1-C4 alkyl groups. 26. A compound of claim 24 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R6a and R7a are identical and are selected from: -C1-C4 alkyl or C3-C6 cycloalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, -COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16RlS, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl, and -aryl or heteroaryl. 27. A compound of claim 24 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R6a and R7a are identical and are -C1-C4 alkyl, each such Cl-C4 alkyl optionally substituted with 1 to 3 substituents independently selected at each occurrence from Cl-C6 alkyl, C3-C6 cycloalkyl, halo, Cl-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, -COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl1 heteroaryl or heterocyclyl. 28. A compound of claim 24 and isomers thereof1 stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R6a is selected from: -H, -C1-C10 alkyl, C3-C10 alkenyl, C3-C10 alkynyl, C1-C10 haloalkyl with 1-10 halogens1 C2-Cg alkoxyalkyl, C3-C6 cycloalkyl, C4 C12 cycloalkylalkyl, C5-C10 cycloalkenyl, or C6-C14 cycloalkenylalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, 03- C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl, -aryl, aryl(C1-C4 alkyl), heteroaryl, heteroaryl(C1-C4 alkyl), heterocyclyl or heterocyclyl(C1-C4 alkyl): R7a is: -C1-C4 alkyl and each such C1-C4 alkyl is substituted with 1-3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl. 29. A compound of claim 24 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein one of R6a and R7a is selected from: -C3-C6 cycloalkyl, each such C3-C6 cycloalkyl optionally substituted with 1-3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl, -aryl1 -heteroaryl or -heterocyclyl, and the other of R6a and R7a is unsubstituted C1-C4 alkyl. 30. A compound of claim 24 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R6a and R7a are independently H or C1-C10 alkyl, each such C1-C10 alkyl optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, R8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl. 31. A compound of claim 16 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein -Ar is phenyl, pyridyl or 2,3-dihydrobenzofuranyl, and each Ar is optionally substituted with 1 to 4 R4 substituents, -R3 is NR6aR7a or OR7 and -R1 and R2 are independently selected from H, 01- alkyl, C3-C6 cycloalkyl, C4-C10 cycloalkylalkyl. 32. A compound of claim 31 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R6a is independently selected from: -H, -C1-C10 alkyl, C3-C10 alkenyl, C3-C10 alkynyl, Cl-Clo haloalkyl with 1-10 halogens, C2-Cg alkoxyalkyl, C3-C6 cycloalkyl, 04- C12 cycloalkylalkyl, C5-C10 cycloalkenyl, or C6-C14 cycloalkenylalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, 03- C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, C02R15, OC(O)R13, NR8COR15, N(COR15)2, NK8OONK16K15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl, -aryl, aryl(Cl-C4 alkyl)-, heteroaryl, heteroaryl(C1-C4 alkyl)1 heterocyclyl or heterocyclyl (01-04 alkyl); R7a is independently selected at each occurrence from: -H, -C5-C10 alkyl, C3-C10 alkenyl, C3-C10 alkynyl, C1-C10 haloalkyl with 1-10 halogens, C2-Cg alkoxyalkyl, C3-C6 cycloalkyl, 04- C12 cycloalkylalkyl, C5-C10 cycloalkenyl, or C6-C14 cycloalkenylalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, 03- C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, oC(o)R13, NR8CoR15, N(CoR15)2, NR8CONR16R15, NR8C02R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl, -aryl, aryl(C1-C4 alkyl), heteroaryl, heteroaryl(C1-C4 alkyl), heterocyclyl or heterocyclyl(C1-C4 alkyl), alternatively, NR6R7 and NR6aR7a are independently piperidine, pyrrolidine, piperazine, Nmethylpiperazine, morpholine or thiomorpholine, each optionally substituted with 1-3 C1-C4 alkyl groups. 33. A compound of claim 31 and isomers thereof, stereoisomeric forms thereof 1 or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R6a and R7a are identical and are selected from: -C1-C4 alkyl or C3-C6 cycloalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo1 C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, -COR15, CO2R15, OC(o)Rl3 NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl, and -aryl or heteroaryl. 34. A compound of claim 31 and isomers thereof1 stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof 1 and pharmaceutically acceptable salt or pro-drug forms thereof wherein R6a and R7a are identical and are -C1-C4 alkyl, each such C1-C4 alkyl optionally substituted with 1 to 3 substituents independently selected at each occurrence from Cl-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, -COR15, CO2R15, OC(O)R13, NR8COR15, N(CORl5)2, NR8CONR16R15, NR8C02R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl. 35. A compound of claim 31 and isomers thereof1 stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R6a is selected from: -H, -C1-C10 alkyl, C3-C10 alkenyl, C3-C10 alkynyl, Cl-C 10 haloalkyl with 1-10 halogens, C2-Cg alkoxyalkyl, C3-C6 cycloalkyl, 04- C12 cycloalkylalkyl, C5-C10 cycloalkenyl, or C6-C14 cycloalkenylalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, 03- C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, oC(o)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl, -aryl, aryl(C1-C4 alkyl), heteroaryl, heteroaryl(C1-C4 alkyl), heterocyclyl or heterocyclyl(C1-C4 alkyl); R7a is: -C1-C4 alkyl and each such C1-C4 alkyl is substituted with 1-3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR151 SH, S(O)nR13, COR15, C02R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl. 36. A compound of claim 31 and isomers thereof, stereoisomeric forms thereof I or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein one of R6a and R7a is selected from: -C3-C6 cycloalkyl, each such C3-C6 cycloalkyl optionally substituted with 1-3 substituents independently selected at each occurrence from C1-C6 alkyl, C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nRl3 COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, NR8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl, -aryl, -heteroaryl or -heterocyclyl, and the other of R6a and R7a is unsubstituted C1-C4 alkyl. 37. A compound of claim 31 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R6a and R7a are independently H or C1-C10 alkyl, each such C1-C10 alkyl optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl1 C3-C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, R8CONR16R15, NR8CO2R13, NR16R15, CONR16R15, aryl, heteroaryl or heterocyclyl. 38. A compound of claim 31 of Formula (50) EMI196.1 FORMULA (50) and isomers thereof, stereoisomeric forms thereof 1 or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof1 selected from the group consisting of: a compound of Formula (50) wherein R3 is -NHCH(n-Pr)2, R is Cl, R4b is H, R4c is Cl, R4d is H and R 4e H; a compound of Formula (50) wherein R3 is -N(Et) (n-Bu), R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -(n Pr)(CH2cPr), R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(CH2CH2OMe)2, R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Et)(n Bu), R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Et) (CH2OMe), R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(CH2OMe)2, R4a is Cl, R4b is H, R@@ is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(Et)2, R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(CH2OEt)2, R4a is Cl, R4b is H, K 4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R is -NHCH(Et)2, R4a is C1, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(Me) (Ph), R4a is C1, R4b is H, R4c is Cl, R4d is H and R4e is K; a compound of Formula (50) wherein R3 is -N(n-Pr)2, R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Et) (n- Pr), R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(CH2OMe)2, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is Me; a compound of Formula (50) wherein R3 is -NHCH(CH2OMe)2, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(CH2CH2OMe)2, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Et) (CH2OMe), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Et)2, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -OEt, R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(Et)2, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(CH2CN)2, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Me) (CH2OMe), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -OCH(Et) (CH2OMe), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(n Pr)(CH2cPr), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Me) (CH2N(Me)2), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(cPr)(CH2CH2CN), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(n Pr) (CH2CH2CN), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(n Bu)(CH2CN), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Et) (CH2OMe), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is Me; a compound of Formula (50) wherein R3 is -NHCH(Et)2, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is Me; a compound of Formula (50) wherein R3 is -N(CH2CH2OMe)2, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is Me; a compound of Formula (50) wherein R3 is -NHCH(CH2OMe)2, R4a is Br, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Et) (CH2OMe), R4a is Br, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (50) wherein. R3 is -N(Et)2, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is Me; a compound of Formula (50) wherein R3 is -NHCH(CH2OEt)2, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is Me; a compound of Formula (50) wherein R3 is -NHCH(CH2CH20Me) (CH20Me)2, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is Me; a compound of Formula (50) wherein R3 is morpholino, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(CH2CH2OMe)2, R4a is Br, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Et)2, R4a is Br, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(Et)2, R4a is Br, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NH(c-Pr), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(CH2OMe)2, R4a is CN, R4b is H, R4c is OMe, R4d is H and R4e is K; a compound of Formula (50) wherein R3 is -N(c Pr) (CH2CH2CN), R4a is Me, R4b is H, K 4c is Me, R4d is H and R4e is Me; a compound of Formula (50) wherein R3 is -NCH(CH2OMe)2, R4a is Me, R4b is H, R4c is Br, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(CH2OMe) (CH2CH2OMe), R4a is Me, R4b is H, R4c is Br, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(CH2OMe)2, R4a is Me, R4b is H, R4@ is OMe, R4d is Me and R4e is H; a compound of Formula (50) wherein R3 is -N(CH2CH2OMe)2, R4a is Me, R4b is H, R4c is OMe, R4d is Me and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Et)2, R4a is Me, R4b is H, R4c is OMe, R4d is Me and R4e is H; a compound of Formula (50) wherein a compound of Formula (50) wherein R3 is -N(Et)2, R4a is Me, R4b is H, R4c is OMe, R4d is Me and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(CH2OMe)2, R4a is Cl, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R is -NHCH(Et) (CH2OMe), R4a is Cl, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(CH2CH2OMe)2, R4a is Cl, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(CH2OMe) (CH2CH2OMe), R4a is Cl, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(c Pr) (CH2CH2CN), R4a is Me, R4b is H, R4c is OMe, R4d is Me and R4e is H; a compound of Formula (50) wherein R3 is -N(c Pr) (CH2CH2CN), R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is (S) NHCH(CH2OMe) (CH2CH2OMe), R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(CH2OMe) (CH2CH2OMe), R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Et)2, R4a is Me, R4b is H, R4c is Br, R4d is H and R4e is K; a compound of Formula (50) wherein R3 is -N(CH2CH2OMe)2, R4a is Me, R4b is H, R4c is Br, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NH(CH2OMe) (CH2-iPr), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(CH2CH2OMe)2, R4a is Me, R4b is K, R4c is H, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(CH2CH2OMe)2, R4a is Me, R4b is H, R4c is NMe2, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(CH2OMe) (n-Pr), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(CH2OEt) (Et), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(CH2OMe) (CH2CH2OMe), R4a is Me, R4b is H, R4c is NMe2, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(Et)2, R4a is Me, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Et)2, R4a is Me, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(CH2CH2OMe)2, R4a is Me, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(CH2OMe)2, R4a is Me, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(Et)2, R4a is Me, R4b is H, R4c is Br, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(Et)21 R4a is Cl, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Et)2, R4a is Cl, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Et)2, R4a is Me, R4b is H, R4c is NMe2, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is (S) NHCH(CH2OMe) (CH2CH2OMe), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(CH2OMe) (CH2CH2OMe), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is (S) NHCH(CH2OMe) (CH2CH2OMe), R4a is Me, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(CH2OMe) (CH2CH2OMe), R4a is Me, R4b is H, R4c is Cl, R4d is H and R4@ is H; a compound of Formula (50) wherein R3 is -N(c Pr) (CH2CH2CN), R4a is Me, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NH(Et) (CH2CN), R4a is Me, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(Et)2, R4a is Me, R4b is Me, K 4c is OMe, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(CH2CH2OMe) (CH2CH2OH), R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(CH2CH2OMe)2, K 4a is Me, R4b is Me, R4c is OMe, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Et)2, R4a is Me, R4b is Me, R4c is OMe, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(CH2c-Pr) (n Pr), R4a is Me, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(c-Pr) (CH2CH2CN), R4a is Me, R4b is Me, R4c is OMe, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH (Et)2, R4a is Cl, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(Et)2, R4a is Cl, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(CH2CH2OMe)2, R4a is Cl, R4b is K, R40 is OMe R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(Et) (CH2OMe), R4a is Cl, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(Et)2, R4a is Cl, R4b is H, R4c is CN, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -N(c Pr) (CH2CH2CN), is Cl, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (50) wherein R3 is -NHCH(CH2OH)2, R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; and a compound of Formula (50) wherein R3 is N(CH2CH2OMe)2, R4a is Me, R4b is H, R4c is OMe, R4d is H and R4e is H a compound of Formula (51) wherein R3 is -N(CH2CH2OMe)2, R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; and a compound of Formula (51) wherein R3 is -NHCH(CH2OMe)2, K 4a is Cl, R4b is H, R40 is Cl, R4d is H and R4e is H. 39. A compound of claim 31 and isomers thereof1 stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof 1 and pharmaceutically acceptable salt or pro-drug forms thereof, wherein said compound is 4-(bis-(2-methoxyethyl)amino)-2,7- dimethyl-3-(2-methyl-4-methoxyphenyl)-[1,5-a]- pyrazolo-1,3,5-triazine. 40. A compound of claim 31 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof 1 wherein said compound is 4-(bis-(2-methoxyethyl)amino)-2,7dimethyl-8-(2,5-dimethyl-4-methoxyphenyl)-[1,5-a]pyrazolo-1,3,5-triazine. 41. A compound of claim 4 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein A is CR. 42. A compound of Formula (2) of claim 41 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof. 48. A compound of claim 42 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein Ar is phenyl, pyridyl or 2,3-dihydrobenzofuranyl and each Ar is optionally substituted with 1 to 4 R4 substituents. 44. A compound of claim 42 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R3 is NR6aR7a or oR7. 45. A compound of claim 42 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein Ar is phenyl, pyridyl or 2,3-dihydrobenzofuranyl, and each Ar is optionally substituted with 1 to 4 R4 substituents, and R3 is NR6aR7a or OR7. 46. A compound of Formula (1) of claim 41 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein Z is CR2 . 47. A compound of claim 46 and isomers thereof1 stereoisomeric forms thereof 1 or mixtures of stereoisomeric forms thereof 1 and pharmaceutically acceptable salt or pro-drug forms thereof wherein Ar is phenyl, pyridyl or 2,3-dihydrobenzofuranyl and each Ar is optionally substituted with 1 to 4 R4 substituents. 48. A compound of claim 46 and isomers thereof1 stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein R3 is NR6aR stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof wherein -Ar is phenyl, pyridyl or 2,3-dihydrobenzofuranyl, and each Ar is optionally substituted with 1 to 4 R4 substituents, -R3 is NR6aR7a or OR7 and -R1 and R2 are independently selected from H, Cl-C4 alkyl, C3-C6 cycloalkyl, C4-C1o cycloalkylalkyl. 52. A compound of claim 51 and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof1 and pharmaceutically acceptable salt or pro-drug forms thereof wherein R6a and R7a are independently H or C1-C10 alkyl, and each such C1-C10 alkyl is optionally substituted with 1 to 3 substituents independently selected at each occurrence from C1-C6 alkyl, 03- C6 cycloalkyl, halo, C1-C4 haloalkyl, cyano, OR15, SH, S(O)nR13, COR15, CO2R15, OC(O)R13, NR8COR15, N(COR15)2, R8CONR16R15, NR8CO2R13, NR16R15, CoNR16Rl5, aryl, heteroaryl or heterocyclyl. 53. A compound of claim 51 of Formula (51) EMI207.1 FORMULA (51) and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof selected from the group consisting of: a compound of Formula (51) wherein R3 is -NHCH(n-Pr)2, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R is -NHCH(CH2OMe)2, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -N(CH2CH2OMe)2, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -N(c Pr) (CH2CH2CN), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -N(CH2CH2OMe)2, R4a is Cl, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NHCH(CH2OMe)2, R4a is Cl, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NHCH(Et)2, R4a is Cl, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -N(Et)2, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -N(n Pr) (CH2CH2CN), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -N(n Bu) (CH2CH2CN), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NHCH(n- Pr) (CH2OMe), R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NHCH(Et)2, R4a is Me, R4b is H, R4c is OMe, R4d is H and R4e is a compound of Formula (51) wherein R3 is -NHCH(CH2OMe)2, R4a is Me, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is (S) -NH(CH2CH2OMe)CH2OMe, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NH(CH2CH2OMe)CH2OMe, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -N(CH2CH2OMe)2, R4a is Me, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NH(Et), R4a is Me, R is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NHCH(n-Pr)2, R4a is Me, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NHCH(CH2OMe)2, R4a is Me, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (51) wherein R is (S) -NH(CH2CH2OMe)CH2OMe, R4a is Me, R4b is H, R4c is Cl, R4d is H and 4e is H; a compound of Formula (51) wherein R3 is -NH(CH2CH2OMe)CH2OMe, R4a is Me, R4b is H, K 4c is Cl, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -N(n Pr) (CH2CH2CN), R4a is Me, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -N(Et)2, R4a is Me, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is (S) -NH(CH2CH2OMe)CH2OMe, R4a is Cl, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NH(CH2CH2OMe)CH2OMe, R4a is Cl, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -N(Et)2, R4a is Cl, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -N(c Pr) (CH2CH2CN), R4a is Me, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -N(c Pr) (CH2CH2CN), R4a is Cl, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NHCH (n Pr) (CH2OMe), R4a is Me, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NHCH (n Pr) (CH2OMe), R4a is Cl, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NHCH(Et)2, R4a is Br, R4b is H, R4c is OMe, R4d is OMe and R4e is H; a compound of Formula (51) wherein R3 is -NHCH(Et)2, R4a is Br, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -N(CH2CH2OMe)2, R4a is Br, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NHCH(CH2OMe)2, R4a is Br, R4b is H, R4c is OMe, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -N(Et)2, R4a is 4c Me, R is H, R is C1, R is H and R is R; a compound of Formula (51) wherein R3 is -N(Et)2, R4a is C1, R4b is H, R4c is OMe, R4d is OMe and R4e is H; a compound of Formula (51) wherein R3 is -NHCH(Et)2, R4a is C1, K4 b is H, R4c is OMe, R4d is OMe and R4e is H; a compound of Formula (51) wherein R3 is -N(CH2CH2OMe)2, R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NHCH(CH2OMe)2, R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -N(Pr)(CH2CH2CN), R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -N(Bu)(Et), R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NHCH(Et)CH2OMe, R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NHCH(Et)2, R4a is Cl, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NHCH(Et)2, R4a is Me, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NHCH(Et)2, R4a is Cl, R4b is H, R4c is Me, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NHCH(Et)2, R4a is Me, R4b is H, R4c is Cl, R4d is H and R4e is H; a compound of Formula (51) wherein R3 is -NEt2, R4a is Me, R4b is H, R4c is OMe, R4d is H and R4e is H; and a compound of Formula (51) wherein R3 is -N (Pr) (CH2CH2CN)I R4a is Me, R4b is K, R4c is OMe, R4d is H and R4e is H. 54. A compound of claim 51 and isomers thereof, stereoisomeric forms thereof1 or mixtures of stereoisomeric forms thereof 1 and pharmaceutically acceptable salt or pro-drug forms thereof, wherein said compound is 7-(3-pentylamino)-2,5-dimethyl-3-(2 methyl-4-methoxyphenyl)-[1,5-a]-pyrazolopyrimidine. 55. A compound of claim 51 and and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt or pro-drug forms thereof, wherein said compound is 7-(Diethylamino)-2,5-dimethyl-3-(2methyl-4-methoxyphenyl-[1,5-a]-pyrazolopyrimidine. 56. A compound of claim 51 and isomers thereof, stereoisomeric forms thereof 1 or mixtures of stereoisomeric forms thereof 1 and pharmaceutically acceptable salt or pro-drug forms thereof 1 wherein said compound is 7- (N- (3-cyanopropyl)-N-propylamino)- 2,5-dimethyl-3-(2,4-dimethylphenyl)-[1,5-a]- pyrazolopyrimidine. 57. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 4. 58. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 24. 59. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 38. 60. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 39. 61. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 40. 62. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 53. 63. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 54. 64. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 55. 65. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 56. 66. A method of treating affective disorder, anxiety, depression, headache, irritable bowel syndrome, post-traumatic stress disorder, supranuclear palsy, immune suppression, Alzheimer's disease, gastrointestinal diseases, anorexia nervosa or other feeding disorder, drug addiction, drug or alcohol withdrawal symptoms, inflammatory diseases, cardiovascular or heart-related diseases, fertility problems, human immunodeficiency virus infections, hemorrhagic stress, obesity, infertility, head and spinal cord traumas, epilepsy, stroke, ulcers, amyotrophic lateral sclerosis, hypoglycemia or a disorder the treatment of which can be effected or facilitated by antagonizing CRF, including but not limited to disorders induced or facilitated by CRF, in mammals comprising administering to the mammal a therapeutically effective amount of a compound of claim 4. 67. A method of treating affective disorder, anxiety, depression, headache, irritable bowel syndrome, post-traumatic stress disorder, supranuclear palsy, immune suppression, Alzheimer's disease, gastrointestinal diseases, anorexia nervosa or other feeding disorder, drug addict ion1 drug or alcohol withdrawal symptoms, inflammatory diseases, cardiovascular or heart-related diseases, fertility problems, human immunodeficiency virus infections, hemorrhagic stress, obesity, infertility, head and spinal cord traumas, epilepsy, stroke, ulcers, amyotrophic lateral sclerosis, hypoglycemia or a disorder the treatment of which can be effected or facilitated by antagonizing CRF, including but not limited to disorders induced or facilitated by CRF, in mammals comprising administering to the mammal a therapeutically effective amount of a compound of claim 24. 68. A method of treating affective disorder, anxiety, depression, headache, irritable bowel syndrome, post-traumatic stress disorder, supranuclear palsy1 immune suppression, Alzheimer's disease, gastrointestinal diseases, anorexia nervosa or other feeding disorder, drug addiction, drug or alcohol withdrawal symptoms1 inflammatory diseases, cardiovascular or heart-related diseases, fertility problems, human immunodeficiency virus infections, hemorrhagic stress, obesity, infertility, head and spinal cord traumas, epilepsy, stroke, ulcers, amyotrophic lateral sclerosis, hypoglycemia or a disorder the treatment of which can be effected or facilitated by antagonizing CRF, including but not limited to disorders induced or facilitated by CRF, in mammals comprising administering to the mammal a therapeutically effective amount of a compound of claim 38. 69. A method of treating affective disorder, anxiety, depression, headache, irritable bowel syndrome, post-traumatic stress disorder, supranuclear palsy, immune suppression, Alzheimer's disease, gastrointestinal diseases, anorexia nervosa or other feeding disorder, drug addiction, drug or alcohol withdrawal symptoms, inflammatory diseases, cardiovascular or heart-related diseases1 fertility problems, human immunodeficiency virus infections, hemorrhagic stress, obesity, infertility, head and spinal cord traumas, epilepsy, stroke, ulcers, amyotrophic lateral sclerosis, hypoglycemia or a disorder the treatment of which can be effected or facilitated by antagonizing CRF, including but not limited to disorders induced or facilitated by CRF, in mammals comprising administering to the mammal a therapeutically effective amount of a compound of claim 39. 70. A method of treating affective disorder, anxiety, depression, headache, irritable bowel syndrome, post-traumatic stress disorder, supranuclear palsy, immune suppression, Alzheimer's disease, gastrointestinal diseases, anorexia nervosa or other feeding disorder, drug addiction1 drug or alcohol withdrawal symptoms, inflammatory diseases, cardiovascular or heart-related diseases, fertility problems, human immunodeficiency virus infections, hemorrhagic stress, obesity, infertility, head and spinal cord traumas, epilepsy, stroke, ulcers, amyotrophic lateral sclerosis, hypoglycemia or a disorder the treatment of which can be effected or facilitated by antagonizing CRF, including but not limited to disorders induced or facilitated by CRE, in mammals comprising administering to the mammal a therapeutically effective amount of a compound of claim 40. 71. A method of treating affective disorder, anxiety, depression, headache, irritable bowel syndrome, post-traumatic stress disorder, supranuclear palsy, immune suppression, Alzheimer's disease, gastrointestinal diseases, anorexia nervosa or other feeding disorder, drug addiction, drug or alcohol withdrawal symptoms1 inflammatory diseases, cardiovascular or heart-related diseases, fertility problems, human immunodeficiency virus infections, hemorrhagic stress, obesity, infertility, head and spinal cord traumas, epilepsy, stroke, ulcers, amyotrophic lateral sclerosis, hypoglycemia or a disorder the treatment of which can be effected or facilitated by antagonizing CRF, including but not limited to disorders induced or facilitated by CRF, in mammals comprising administering to the mammal a therapeutically effective amount of a compound of claim 53. 72. A method of treating affective disorder, anxiety, depression, headache, irritable bowel syndrome, post-traumatic stress disorder, supranuclear palsy, immune suppression, Alzheimer's disease, gastrointestinal diseases, anorexia nervosa or other feeding disorder, drug addiction, drug or alcohol withdrawal symptoms, inflammatory diseases, cardiovascular or heart-related diseases1 fertility problems, human immunodeficiency virus infections, hemorrhagic stress, obesity, infertility, head and spinal cord traumas, epilepsy, stroke, ulcers, amyotrophic lateral sclerosis, hypoglycemia or a disorder the treatment of which can be effected or facilitated by antagonizing CRF, including but not limited to disorders induced or facilitated by CRF, in mammals comprising administering to the mammal a therapeutically effective amount of a compound of claim 54. 73. A method of treating affective disorder, anxiety, depression, headache, irritable bowel syndrome, post-traumatic stress disorder, supranuclear palsy1 immune suppression, Alzheimer's disease, gastrointestinal diseases, anorexia nervosa or other feeding disorder, drug addiction, drug or alcohol withdrawal symptoms, inflammatory diseases, cardiovascular or heart-related diseases1 fertility problems, human immunodeficiency virus infections, hemorrhagic stress, obesity, infertility, head and spinal cord traumas, epilepsy, stroke, ulcers, amyotrophic lateral sclerosis, hypoglycemia or a disorder the treatment of which can be effected or facilitated by antagonizing CRF, including but not limited to disorders induced or facilitated by CRF, in mammals comprising administering to the mammal a therapeutically effective amount of a compound of claim 55. 74. A method of treating affective disorder, anxiety, depression, headache, irritable bowel syndrome, post-traumatic stress disorder, supranuclear palsy, immune suppression, Alzheimer's disease, gastrointestinal diseases, anorexia nervosa or other feeding disorder, drug addiction, drug or alcohol withdrawal symptoms, inflammatory diseases, cardiovascular or heart-related diseases, fertility problems, human immunodeficiency virus infections, hemorrhagic stress, obesity, infertility, head and spinal cord traumas, epilepsy, stroke, ulcers, amyotrophic lateral sclerosis, hypoglycemia or a disorder the treatment of which can be effected or facilitated by antagonizing CRF, including but not limited to disorders induced or facilitated by CRF, in mammals comprising administering to the mammal a therapeutically effective amount of a compound of claim 56.

Inventors: ARVANITIS ARGYRIOS GEORGIOUS, CHORVAT ROBERT JOHN, ARVANITIS, ARGYRIOS, GEORGIOUS, CHORVAT, ROBERT, JOHN
Applicants: DU PONT MERCK PHARMA, THE DU PONT MERCK PHARMACEUTICAL COMPANY
Application year: 1997
Main classification: C07D487
IPC codes: C07D487