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 heart- related diseases and colonic hypersensitivity associated with psychopathological disturbance and stress, by administration of certain [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] -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 -1- [ . 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)]. 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 [CB. Nemeroff et al . , .Science 226:1342 (1984); CM. Banki et al . , Am. J. Psychiatry 144:873 (1987); R.D. France et al . , Biol . Psychiatry 28:86 (1988); M. Arato et al . , Biol Psychiatry 25:355 (1989)] . Furthermore, the density of CRF receptors is significantly decreased in the frontal cortex of suicide victims, consistent with a hypersecretion of CRF [CB. Nemeroff et al . , Arch. Gen . Psychiatry 45:577 (1988)] . In addition, there is a blunted adrenocorticotropin (ACTH) response to CRF (i.v. administered) observed in depressed patients [P.W. Gold et al., Am J. Psychiatry 141:619 (1984); F. Holsboer et al . , Psychoneuroendocrinology 9:147 (1984); P.W. Gold et al . , New Eng. J. Med. 314:1129 (1986)]. Preclinical studies in rats and non-human primates provide additional support for the hypothesis that hypersecretion of CRF may be involved in the symptoms seen in human depression [R.M. Sapolsky, Arch . Gen . Psychiatry 46:1047 (1989)] . There is preliminary evidence that tricyclic antidepressants can alter CRF levels and thus modulate the numbers of CRF receptors in brain [Grigoriadis et al . , Neuropsychopharmacology 2:53 (1989) ] . There has also been a role postulated for CRF in the etiology of anxiety-related disorders. CRF produces anxiogenic effects in animals and interactions between benzodiazepine / non- benzodiazepine anxiolytics and CRF have been demonstrated in a variety of behavioral anxiety models [D.R. Britton et al . , Life Sci . 31:363 (1982); C . 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 [CW. 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 -3- 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 (Rol5-1788) , which was without behavioral activity alone in the operant conflict test, reversed the effects of CRF in a dose-dependent manner while the benzodiazepine inverse agonist (FG7142) enhanced the actions of CRF [K.T. Britton et al . , Psychopharmacology 94:306 (1988)] . The mechanisms and sites of action through which the standard anxiolytics and antidepressants produce their therapeutic effects remain to be elucidated. It has been hypothesized however, that they are involved in the suppression of the CRF hypersecretion that is observed in these disorders. Of particular interest is that preliminary studies examining the effects of a CRF receptor antagonist (α - helical CRF9-41) in a variety of behavioral paradigms have demonstrated that the CRF antagonist produces "anxiolytic-like" effects qualitatively similar to the benzodiazepines [for review see G.F. Koob and K.T. Britton, In: Corticotropin-Releasing Factor: Basic and Clinical Studies of a Neuropeptide, E.B. De Souza and CB. Nemeroff eds., CRC Press p221 (1990)]. Several publications describe corticotropin releasing factor antagonist compounds Dl* 1 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-l, 3,5- triazines, [1 , 5-a] -pyrazolo-pyrimidines and [1,5-a]- 1, 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 where R 1 is OH or alkanoyl, R 2 is H, OH, or SH, and R 3 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 -5- ( ? 2 ) n where A is CH or N, R° and R 3 are H or alkyl, and R 1 and R 2 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: where Rl is CH 3 , C 2 H 5 or C 6 H 5 , X is H, C 6 H 5 , m-CH 3 C 6 H 4 , CN, COOEt, Cl, I or Br, Y is H, C 6 H 5 , o-CH 3 C 6 H 4 , or p- CH 3 C 6 H 4 , and Z is OH, H, CH 3 , C 2 H 5 , C 6 H 5 , n-C 3 H 7 , i-C 3 H 7 , SH, SCH 3 , NHC 4 H 9 , or N(C 2 H 5 ) 2 , and states that the compounds are c-AMP phosphodiesterase inhibitors useful as bronchodilators . US 3,995,039 discloses pyrazolotriazines of the formula: NR 2 R 3 where R 1 is H or alkyl, R 2 is H or alkyl, R 3 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 / 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 -7- S N Ar 0 R s where X is O or S, Ar is a phenyl, naphthyl, pyridyl or thienyl group, Rβ-Rs are H, alkyl, etc., and R 9 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 ■ A Ri N " where A can be N, B can be CR 3 , R 3 can be phenyl or substituted phenyl, etc., R is -N(R 4 )S0 2 Rs or _ S0 2 (R 6 )R and Ri and R 2 can be taken together to form Z Y z Y X D or 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 where Z is H, OH, CH 3 , C 2 H 5/ C 6 H 5 , n-C 3 H 7 , iso-C 3 H 7 , SH, SCH 3 , NH(n-C 4 H 9 ), or N(C H 5 ) 2 , R is H or CH 3 , and R λ is CH 3 or C 2 H 5 . 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 ■ A- where Q is carbonyl or sulfonyl, n is 0 or 1, A is a single bond, alkylene or alkenylene, R 1 is H, alkyl, etc., R 2 is naphthyl, cycloalkyl, heteroaryl, substituted phenyl or phenoxy, R 3 is H, alkyl or phenyl, R 4 is H, alkyl, alkoxycarbonyl , phenylalkyl, optionally phenylthio-substituted phenyl, or halogen, R 5 and R 6 are H or alkyl . EP 0 591 528 (Otsuka, 1991) discloses anti- inflammatory use of pyrazolopyrimidines represented by the formula where Rj_, R 2 , R 3 and R 4 are H, carboxyl, alkoxycarbonyl, optionally substituted alkyl, cycloalkyl, or phenyl, R 5 is SR 6 or NR 7 Ra, Re is pyridyl or optionally substituted phenyl, and R and Rs 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 •10- HO ' 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 C 6 H 5 where R 1 is CF 3 , C 2 F 5 , or C 6 H 4 F, and R 2 is CH 3 , C 2 H 5 , CF 3/ or C 6 H 4 F. Maquestiau et al . , Bull. Soc . Belg., vol.101, no. 2, 1992, pages 131-136 discloses a pyrazolo [1 , 5- a]pyrimidine of the formula -11- C S 6H n 5 Ibrahim et al . , Arch. Pharm. (weinheim) 320, 487-491 (1987) discloses pyrazolo [1 , 5-a] pyrimidines of the formula CH 3 where R is NH2 or OH and Ar is 4-phenyl-3-cyano-2- aminopyrid-2-yl . Other references which disclose azolopyrimidines indued 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 -12- 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 suppression, Alzheimer'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 -13- inappropriate antidiarrhetic hormone (ADH) ; obesity; infertility; head traumas; spinal cord trauma; ischemic neuronal damage (e.g. , 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.g. , 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.g. , 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 CRF 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 heart -related diseases and colonic hypersensitivity associated with psychopathological disturbance and stress in a mammal . •14- According to another aspect, the present invention provides novel compounds 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 CRF 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 of a potential pharmaceutical to bind to the CRF receptor. DETAILED DESCRIPTION OF INVENTION [1] The present invention provides compounds of Formula (50) -15- R 3 N N- H„C y y CH 3 R 4e R 4a R 4c FORMULA (50) and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt forms thereof, selected from the group: a compound of Formula (50) wherein R 3 is - NHCH(CH 2 CH 2 OMe) (CH 2 OMe) , R 4 is Me^ R 4b ig H^ R 4c is Me, R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is -NHCH(Et)2, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is 2- ethylpiperid-1-yl, R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is cyclobutyl - amino, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)CH 2 CH=CH 2 R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et)CH 2 CH=CH 2 . R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; -16- a compound of Formula (50) wherein R 3 is N(Me)CH2cPr, R 4a is Me, R 4b is H, R 4c is OMe, R d is H and R 4 is H; a compound of Formula (50) wherein R 3 is N(Et)CH 2 cPr ; R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4 is H; a compound of Formula (50) wherein R 3 is N(Pr)CH 2 cPr , R R 44aa iis Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Pr R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Et R 4a iiss Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Bu ( R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)propargyl, R 4a 1S Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et)propargyl, R 4a 1S M e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(CH 3 )CH(CH 3 )CH 3 , R a i s M e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH 2 CH 2 OMe) - CH 2 CH=CH 2 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)M e/ R 4a 1S Me, R 4b is H, R 4c is OMe, -17- R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N ( CH 2 CH 2 OMe ) Et, R 4a is Me, R b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N ( CH 2 CH 2 OMe ) Pr, R 4a is M e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH CH 2 OMe) - CH 2 cPr, R 4 is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH ( CH 3 ) CH 2 CH 3/ R a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(cPr) , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is 2- ethylpiperid-1-yl, R 4a i s M e, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is cyclobutyl - amino, R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)CH 2 CH=CH 2 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et)CH 2 CH=CH 2 R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)CH 2 cPr, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; -18- a compound of Formula (50) wherein R 3 is N(Et)CH 2 cPr R R 44aa iis Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Pr)CH 2 cPr R R 44aa iis Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Pr R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Et R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Bu R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)propargyl, R 4a i s M e, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et)propargyl, R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(CH 3 )CH(CH 3 )CH 3 , R 4 is M e, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH 2 CH 2 OMe) - C CHH 22 CCHH==CCHH 22 , R R 44aa ii s Me, R 4b is H, R 4c is OMe, R 4d is e and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Me, R 1S Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Et, R 4a 1S Me, R 4b is H, R 4c is OMe, ■19- R 4d is Me and R 4e is H ; . a compound of Formula (50) wherein R 3 is N ( CH 2 CH 2 OMe)Pr, R 4a is Me , R 4 ^ is H , R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH 2 CH 2 OMe) - CH 2 cPr, R 4a is M e, R 4 ^ is H , R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(CH 3 ) CH 2 CH 3 , R 4a is M e , R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is -NHCH(Et) 2 , R R 44aa iis Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(cPr)2, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is -NHCH(Et) 2 , R R 44aa iis OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is 2- ethylpiperid-1-yl, R 4a i s OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is cyclobutyl - amino, R 4a i s OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)CH 2 CH=-CH 2 , R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et)CH 2 CH=CH 2 , R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; -20- a compound of Formula (50) wherein R 3 is N(Me)CH 2 cPr R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et)CH2cPr R R 44aa iis OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Pr)CH 2 cPr, R R 44aa iis OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Pr R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Et R 4a iiss OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Bu R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N ( Me ) propargyl, R 4a i s OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et)propargyl, R 4a i s OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(CH 3 )CH(CH 3 )CH 3 , R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH 2 CH 2 OMe) - CH 2 CH=CH 2 , R 4 is OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Me, R 4a i s OMe, R 4b is H, R 4c is OMe, -21- R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N ( CH 2 CH 2 OMe ) Et, R a is OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Pr, R 4a is 0 Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH2CH 2 OMe) - CH 2 cPr, R 4 is OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH ( CH 3 )CH 2 CH 3 , R 4a is 0 Me , R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(cPr) 2 R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH 2 CH 2 OMe) 2 , R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(Et) 2 , R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et) 2 , R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is 2- ethylpiperid-1-yl, R 4a i s OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is cyclobutyl amino, R 4a is OMe, R 4b is H, R 4c is OMe, R 4d i and R 4e is H; a compound of Formula (50) wherein R 3 is -22- N ( Me ) CH 2 CH=CH 2 , R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N ( Et ) CH 2 CH=CH 2 , R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)CH2cPr, R R4 4aa is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et)CH 2 cPr R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Pr)CH 2 cPr R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Pr, R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Et, R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Bu, R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)propargyl, R 4a 1S OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et)propargyl, R 4a ιg OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(CH 3 )CH(CH 3 )CH 3 , R 4a is 0 Me , R 4b is H, R 4c is OMe, R is Me and R 4e is H; -23- a compound of Formula (50) wherein R 3 is N (CH 2 CH 2 OMe) - CH 2 CH=CH 2 , R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R e is H; a compound of Formula (50) wherein R 3 is N ( CH 2 CH 2 OMe ) Me, R a is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe ) Et, R a is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe ) Pr, R 4 is 0 Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH 2 CH 2 OMe) - CH cPr, R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(CH 3 )CH 2 CH 3 , R 4a is 0 Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(cPr) 2 , R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH2CH 2 OMe) 2 , R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(Et)2, R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et) 2 , R 4a i s OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; -24- a compound of Formula (50) wherein R 3 is 2- ethylpiperid-1-yl, R 4a is Me , R 4b i s H , R 4c is OMe, R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is cyclobutyl - amino, R 4a i s M e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is N(Me ) CH 2 CH=CH 2 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is N(Et ) CH 2 CH=CH 2 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is N(Me)CH 2 cPr, R 4a is Me, R 4b is H, R 4c is OMe, R d is H and R 4e is Me ; a compound of Formula (50) wherein R 3 is N(Et)CH2cPr, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is Me ; a compound of Formula (50) wherein R 3 is N(Pr)CH2cPr, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is Me ; a compound of Formula (50) wherein R 3 is N(Me)Pr, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is N(Me)Et, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is N(Me)Bu, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is N(Me)propargyl, R 4a _ s Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is Me; -25- a compound of Formula (50) wherein R 3 is N ( Et ) propargyl, R 4a is M e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is NHCH(CH 3 )CH(CH 3 )CH 3 , R 4 is Me , R 4 ^ is H , R 4c is OMe, R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is N(CH 2 CH2θMe) CH 2 CH=CH 2 R 4 i s Me, R 4b is H, R 4c is OMe, R 4d i- H ' and R 4e is Me; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Me, R a is M e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Et, R 4 is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Pr, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is N (CH 2 CH OMe) - CH 2 cPr, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is NHCH(CH 3 )CH 2 CH 3 , R 4a is Me , R 4b is H, R 4c is OMe, R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is NHCH(Et) 2 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is NHCH(cPr) 2 , R R 44aa iiss Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is Me; -26- a compound of Formula (50) wherein R 3 is NHCH(Et) 2 , R 4a iiss MMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is 2- ethylpiperid-1-yl, R 4a is Me , R 4b is H , R 4c i .s ∑ OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is cyclobutyl - amino, R 4a i s Me , R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N ( Me ) CH 2 CH=CH 2 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(Et)CH 2 CH=CH 2 , R 4 i s Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(Me)CH 2 cPr, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(Et)CH 2 cPr, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(Pr)CH 2 cPr, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(Me)Pr, R 4a iiss VM.e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(Me)Et, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(Me)Bu, R 4a iiss VM.e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; -27- a compound of Formula (50) wherein R 3 is N ( Me ) propargyl, R 4a i s M e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N ( Et ) propargyl, R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is NHCH(CH 3 )CH(CH 3 )CH 3 , R 4a is M e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N (CH 2 CH OMe) - CH 2 CH=CH 2 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Me, R a is M e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Et, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Pr, R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N (CH 2 CH 2 OMe) ■ - CH 2 cPr, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is NHCH(CH 3 )CH 2 CH 3 , R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe ; a compound of Formula (50) wherein R 3 is NHCH(cPr) 2 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e i s OMe; a compound of Formula (50) wherein R 3 is N (CH2CH2θMe) 2 , -28- R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe ; a compound of Formula (50) wherein R 3 is NHCH(Et) 2 R 4a iiss MMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(Et) 2 R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is NHCH(Et) 2 R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is 2- ethylpiperid-1-yl, R 4a i s C l , R 4b is H, R 4c i OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is cyclobutyl- amino, R 4a i s cl , R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(Me)CH 2 CH=CH 2 , R 4a is C l , R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(Et ) CH 2 CH=CH 2 , R 4a is Cl , R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe ; a compound of Formula (50) wherein R 3 is N(Me)CH 2 cPr, R 4a is Cl, R 4b is H, R 4c is OMe, R d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(Et)CH 2 cPr, R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(Pr)CH 2 cPr, R 4a i s cl, R 4 is H, R 4c is OMe, R 4d is H and R 4e is OMe; -29- a compound of Formula (50) wherein R 3 is N(Me)Pr R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(Me)Et, R 4a iiss CCl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(Me)Bu, R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(Me)propargyl, R 4a ± s C l, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(Et)propargyl, R 4a i s C l, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is NHCH(CH 3 )CH(CH 3 )CH 3 , R 4a is C l , R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(CH CH 2 OMe) - CH 2 CH=CH 2 , R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Me, R 4a is C l , R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Et, R 4a i s cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Pr, R 4a 1S cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N (CH 2 CH OMe) - CH2cPr, R 4a is cl, R 4b is H, R 4c is OMe, R 4d is H •30- and R 4e is OMe; a compound of Formula (50) wherein R 3 is NHCH ( CH 3 ) CH 2 CH 3/ R 4 is C l , R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is NHCH(cPr) 2 R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe ; a compound of Formula (50) wherein R 3 is N (CH CH OMe) 2 R R 44aa iiss ■ Cl, ,4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is NHCH(Et)2, R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(Et)2, R 4a is cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is NHCH(Et)2, R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is 2- ethylpiperid-1-yl, R 4a i s cl , R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is cyclobutyl - amino, R 4a is Cl , R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)CH 2 CH=CH 2/ R 4a is cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et)CH 2 CH=CH 2 , R 4a i s cl , R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)CH 2 cPr, -31- R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et)CH 2 cPr R R 44aa iis Cl, R 4b is H, ,4c IS OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Pr)CH 2 cPr R R 44aa iis Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Pr R 4a iiεs Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Et R 4a iiεs Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Bu, R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)propargyl, R 4a i s Cl , R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et)propargyl, R 4a i s Cl , R 4b is H, R 4c is OMe, R 4d i s H and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(CH 3 )CH(CH 3 )CH 3 , R 4a is cl , R b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH 2 CH2θMe) - CH 2 CH=CH 2 , R 4a is cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Me, R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; -32 a compound of Formula (50) wherein R 3 is N ( CH 2 CH 2 OMe ) Et, R 4a is Cl , R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N ( CH 2 CH 2 OMe)Pr, R 4a is Cl , R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH CH 2 OMe) - CH 2 cPr, R 4a is Cl, R 4b is H, R c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(CH 3 )CH 2 CH 3 , R 4a is C l , R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(cPr) 2 , R R 4 4 a a iis Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH 2 CH 2 OMe) 2 , R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(Et)2, R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et) 2 , R 4a is cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H. a compound of Formula (50) wherein R 3 is NHCH(Et) 2 , R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is 2- ethylpiperid-1-yl, R 4a is Cl , R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is cyclobutyl - amino, R 4a i s cl , R 4b is H, R 4c is OMe, R 4d is F -33- and R 4e is H; a compound of Formula (50) wherein R 3 is N ( Me ) CH 2 CH=CH 2 , R 4a is Cl , R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N ( Et ) CH 2 CH=CH 2 , R 4 is Cl, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)CH 2 cPr R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et)CH2cPr R R 44aa iis Cl, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N(Pr)CH2cPr, R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Pr, R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Et, R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Bu, R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)propargyl, R 4a ± s cl, R b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is NH(CH(CH 3 )CH(CH 3 )CH 3 , R 4a is Cl , R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH CH 2 OMe) - -34- CH 2 CH=CH 2 , R 4a is Cl, R 4b is H, R 4c is OMe, R4d F and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe ) Me, R 4a is cl, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe ) Et, R 4a is Cl , R 4b is H, R 4c is OMe, R 4 is F and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Pr, R 4a is cl , R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH2CH2θMe) - CH 2 cPr, R is Cl, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is NH(CH(CH 3 )CH 2 CH 3 , R 4a is C l , R 4b is F, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(cPr) 2 , R 4a is cl, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH2CH2θMe) 2 , R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(Et) 2 , R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et) 2 , R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H. a compound of Formula (50) wherein R 3 is NHCH(Et) 2 , R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; -35- a compound of Formula (50) wherein R 3 is 2- ethylpiperid-1-yl, R 4 is C l , R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is cyclobutyl- amino, R 4a i s cl, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N ( Me ) CH 2 CH=CH 2 , R 4a is Cl , R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N ( Et ) CH 2 CH=CH 2 , R 4a is Cl , R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)CH 2 cPr, R R 44aa iis Cl, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et)CH 2 cPr, R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Pr)CH 2 cPr, R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Pr, R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Et, R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Bu, R 4a iisε Cl, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is -36- N(Me)propargyl, R 4a i s Cl , R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is NH(CH(CH 3 )CH(CH 3 )CH 3 , R 4 * is cl R b ig H# R 4c ig OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH 2 CH OMe) - CH 2 CH=CH 2 , R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Me, R 4a is cl , R 4b is H , R 4c is OMe, -4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Et, R 4a is C l , R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Pr, R 4a is Cl , R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH 2 CH 2 OMe) - CH 2 cPr, R 4 is C l , R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(CH 3 )CH 2 CH 3 , R 4a is Cl , R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(cPr) 2 , R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is (CH2CH2θMe) 2 , R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(Et)2, R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is -37- H; a compound of Formula (50) wherein R 3 is N(Et) 2 , R 4a is Cl, R b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(Et) 2 R 4a is Br, R b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is 2- ethylpiperid-1-yl, R 4a 3 B r, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is cyclobutyl- amino, R 4a i s Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)CH 2 CH=CH 2 , R 4 i s Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et)CH 2 CH=CH 2 , R 4a ig Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)CH 2 cPr, R 4a is Br, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et)CH 2 cPr, R 4a is Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein ' R 3 is N(Pr)CH2cPr, R 4a is Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Pr, R 4a is Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; -38- a compound of Formula (50) wherein R 3 is N(Me)Et R 4a iiss Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Bu, R 4a is Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)propargyl, R 4 i s Br, R 4b is H, R 4c is OMe, ' R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is NH(CH(CH 3 )CH(CH 3 )CH 3 , R a is B r, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH2CH2θMe) - CH 2 CH=CH 2 , R 4a is Br, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Me, R 4a is Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Et, R 4a ig B r, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Pr, R 4a is B r, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH 2 CH OMe) - CH 2 cPr, R 4a i s Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is NH(CH(CH 3 )CH 2 CH 3 , R 4a ig B r, R 4b is H, R 4c is OMe, R d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(cPr)2, -39- R 4a is Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH 2 CH 2 OMe ) 2 , R 4a is Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(Et) 2 , R 4a liεs Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et) 2 , R 4a is Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(Et) / R 4a is Me, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is 2- ethylpiperid-1-yl, R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is .H; a compound of Formula (50) wherein R 3 is cyclobutyl - amino, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)CH 2 CH=CH 2 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et)CH 2 CH=CH 2 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)CH 2 cPr, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et)CH cPr, -40- R 4a is Me, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Pr)CH2cPr, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Pr, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Et, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Bu, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)propargyl, R 4a i s M e, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is NH(CH(CH 3 )CH(CH 3 )CH 3 , R a is B r, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH2CH2θMe) - CH 2 CH=CH 2 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Me, R 4a is M e, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Et, R 4a i 3 Me, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Pr, R 4 is Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; -41. a compound of Formula (50) wherein R 3 is N(CH2CH 2 OMe) CH 2 cPr, R 4*aa i s M e, R 4b is H, R 4c is OMe, R 4d .s OMe and R 4e is H; a compound of Formula (50) wherein R 3 is NH ( CH ( CH 3 )CH 2 CH 3 , R 4a is M e, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(cPr)2 R 4a is Me, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH2CH2θMe) 2 R 4a is Me, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(Et)2, R 4a iiss MMee,, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; and a compound of Formula (50) wherein R 3 is N(Et)2, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H. [2] The present invention also provides compounds of Formula (60) 3 .N CH 3 N Ar FORMULA (60) and isomers thereof, stereoisomeric forms thereof, or -42- mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt forms thereof, selected from the group: a compound of Formula (60) wherein R 3 is NHCH(Et)2, Ar is 6-dimethylamino-4-methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is 2- ethylpiperid-1-yl, Ar is 6-dimethylamino-4- methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is cyclobutyl - amino, Ar is 6 -dimethylamino-4 -methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N ( Me ) CH2CH=CH2, Ar is 6-dimethylamino-4 - methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N(Et)CH2cPr, Ar is 6-dimethylamino-4 -methylpyrid-3 -yl; a compound of Formula (60) wherein R 3 is N(Pr)CH 2 cPr, Ar is 6-dimethylamino-4-methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Me)Pr, Ar is 6-dimethylamino-4 -methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N(Me)Et, r is 6 -dimethylamino-4 -methylpyrid-3 -yl; a compound of Formula (60) wherein R 3 is N(Me)Bu, Ar is 6-dimethylamino-4-methylpyrid-3-yl ; -43- a compound of Formula (60) wherein R 3 is N ( Me ) propargyl, A r is 6-dimethylamino-4- methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N ( Et ) propargyl, A r is 6-dimethylamino-4- methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is NH ( CH ( CH 3 ) CH(CH 3 )CH 3 , A r is 6-dimethylamino-4- methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is (CH 2 CH 2 OMe) - CH2CH=CH 2 , r is 6-dimethylamino-4-methylpyrid-3- yl; a compound of Formula (60) wherein R 3 is N(CH 2 CH 2 OMe)Me, Ar is 6-dimethylamino-4- methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(CH 2 CH 2 OMe)Et, Ar is 6-dimethylamino-4 - methylpyrid- 3 -yl ; a compound of Formula (60) wherein R 3 is N(CH 2 CH 2 OMe)Pr, A r is 6-dimethylamino-4- methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N (CH 2 CH2θMe) - CH 2 cPr, Ar is 6 -dimethylamino-4 -methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is NH(CH(CH 3 )CH 2 CH 3 , A r is 6 -dimethylamino-4- -44- methylpyrid- 3 -yl ; a compound of Formula (60) wherein R 3 is NHCH(cPr)2 Ar is 6-dimethylamino-4-methylpyrid-3-yl; a compound of Formula (60) wherein R 3 is N (CH2CH2θMe) 2 Ar is 6-dimethylamino-4-methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is NHCH(Et)2 Ar is 6-dimethylamino-4-methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Et) 2 Ar is 6-dimethylamino-4 -methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is 2- ethylpiperid-1-yl, Ar is 6-dimethylamino-4- methylpyrid- 3 -yl ; a compound of Formula (60) wherein R 3 is cyclobutyl - amino, Ar is 6-dimethylamino-4-methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Me)CH2CH=CH 2 , A r is 6-dimethylamino-4- methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N(Et)CH 2 cPr, Ar is 6-dimethylamino-4-methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Pr)CH cPr, Ar is 6-dimethylamino-4-methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Me)Pr, Ar is .45. 6-dιmethylamιno-4-methylpyrιd-3-yl ; a compound of Formula (60) wherein R 3 is N(Me)Et, Ar is 6 -dimethylammo-4 -methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N(Me)Bu, Ar is 6 -dimethylamino-4 -methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N ( Me ) propargyl, Ar is 6-dιmethylammo-4- methylpyπd- 3 -yl ; a compound of Formula (60) wherein R 3 is NH(CH(CH 3 )CH(CH 3 )CH 3 , A r is 6-dimethyl mmo-4 - methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N (CH 2 CH 2 OMe) • CH2CH=CH2, Ar is 6 -dιmethylammo-4 -methylpyrid-3- yi ; a compound of Formula (60) wherein R 3 is N(CH 2 CH 2 OMe)Me, Ar is 6-dιmethylamιno-4- methylpyrιd-3-yl; a compound of Formula (60) wherein R 3 is N(CH 2 CH 2 OMe)Et, Ar is 6-dιmethylammo-4- methylpyrιd-3-yl ; a compound of Formula (60^ wherein R 3 is N(CH CH 2 OMe)Pr, Ar is 6-dιmethylammo-4- methylpyrιd-3-yl ; a compound of Formula (60) wherein R 3 is N(CH2CH2θMe) -46- CH2cPr, Ar is 6-dimethylamino-4-methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is NH ( CH ( CH 3 ) CH 2 CH 3 , A r is β-dimethylamino-4- methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is NHCH(cPr) 2 , A r is 6-dimethylamino-4-methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N (CH2CH2θMe) 2 Ar is 6 -dimethylamino-4 -methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is NHCH(Et)2, Ar is 6 -dimethylamino-4 -methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N(Et) 2 , Ar is 6-dimethylamino-4-methylpyrid-3-yl . a compound of Formula (60) wherein R 3 is 2- ethylpiperid-1-yl, Ar is 6- methoxy -4- methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is cyclobutyl - amino, Ar is 6- methoxy -4-methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Me)CH 2 CH=CH 2 , Ar is 6- methoxy -4-methylpyrid-3- yi; a compound of Formula (60) wherein R 3 is N(Et)CH2cPr, Ar is 6- methoxy -4 -methylpyrid- 3 -yl ; -47- a compound of Formula (60) wherein R 3 is N(Pr)CH2cPr, Ar is 6- methoxy -4 -methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N(Me)Pr, Ar is 6- methoxy -4 -methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N(Me)Et, Ar is 6- methoxy -4 -methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N(Me)Bu, Ar is 6- methoxy -4 -methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N ( Me)propargyl, r is 6- methoxy -4 -methylpyrid-3- yl; a compound of Formula (60) wherein R 3 is N(Et)propargyl, Ar is 6- methoxy -4 -methylpyrid-3- yi ; a compound of Formula (60) wherein R 3 is NHCH(CH 3 )CH(CH 3 )CH 3 , A r is 6- methoxy -4- methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N (CH 2 CH2θMe) - CH 2 CH=CH 2 , Ar is 6- methoxy -4 -methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N(CH CH 2 OMe)Me, Ar is 6- methoxy -4 -methylpyrid- 3- yl ; a compound of Formula (60) wherein R 3 is -48- N ( CH 2 CH 2 OMe ) Et, A r is 6- methoxy -4 -methylpyrid-3- yi ; a compound of Formula (60) wherein R 3 is N ( CH 2 CH2θMe ) Pr, A r is 6- methoxy -4-methylpyrid-3- yi ; a compound of Formula (60) wherein R 3 is N (CH 2 CH OMe) - CH 2 cPr, Ar is 6- methoxy -4 -methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is NHCH ( CH 3 ) CH 2 CH 3 , A r is 6- methoxy -4-methylpyrid- 3-yl; a compound of Formula (60) wherein R 3 is NHCH(cPr)2 Ar is 6- methoxy -4 -methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is (CH 2 CH 2 OMe) 2 , Ar is 6- methoxy -4 -methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is NHCH(Et) 2 Ar is 6- methoxy -4 -methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Et) 2/ Ar is 6- methoxy -4-methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is 2- ethylpiperid-1-yl, Ar is 4-methoxy-6-methylpyrid- 3-yl; a compound of Formula (60) wherein R 3 is cyclobutyl- amino, Ar is 4 -methoxy- 6 -methylpyrid-3-yl ; -49- a compound of Formula (60) wherein R 3 is N ( Me ) CH2CH=CH 2 , A r is 4 -methoxy- 6 -methylpyrid-3- yi; a compound of Formula (60) wherein R 3 is N(Et)CH 2 cPr Ar is 4 -methoxy-6 -methylpyrid-3 -yl; a compound of Formula (60) wherein R 3 is N(Pr)CH2cPr Ar is 4 -methoxy-6 -methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N(Me)Pr, Ar is 4 -methoxy-6 -methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N(Me)Et, Ar is 4-methoxy-6-methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Me)Bu, r is 4 -methoxy-6-methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N(Me)propargyl, A r is 4 -methoxy- 6-methylpyrid-3 - yl; a compound of Formula (60) wherein R 3 is NHCH(CH 3 )CH(CH 3 )CH 3 , A r is 4-methoxy-6- methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N (CH2CH2θMe) - CH2CH=CH2, Ar is 4 -methoxy- 6-methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N(CH2CH2θMe)Me, Ar is 4 -methoxy-6-methylpyrid-3 -50- yl ; a compound of Formula (60) wherein R 3 is N ( CH 2 CH 2 OMe ) Et, A r is 4 -methoxy-6 -methylpyrid-3- yi; a compound of Formula (60) wherein R 3 is N ( CH 2 CH 2 OMe ) Pr, Ar is 4-methoxy-6-methylpyrid-3- yl ; a compound of Formula (60) wherein R 3 is N (CH CH 2 OMe) - CH cPr, Ar is 4 -methoxy- 6-methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is NH ( CH(CH )CH 2 CH 3 , Ar is 4 -methoxy-6-methylpyrid-3 - yl ; a compound of Formula (60) wherein R 3 is NHCH(cPr) , r is 4 -methoxy-6 -methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N (CH 2 CH 2 OMe) 2 , Ar is 4 -methoxy-6 -methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is NHCH(Et) , Ar is 6- methoxy -4-methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Et) 2 , Ar is 4 -methoxy- 6-methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is 2- ethylpiperid-1-yl, Ar is 4 , 6-dimethylpyrid-3-yl ; -51- a compound of Formula (60) wherein R 3 is cyclobutyl - amino, Ar is 4 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N ( Me ) CH2CH=CH 2 , A r is 4 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Et)CH 2 cPr Ar is 4 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Pr)CH2cPr Ar is 4 , 6-dimethylpyrid-3-yl; a compound of Formula (60) wherein R 3 is N(Me)Pr, Ar is 4 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Me)Et Ar is 4 , 6-dimethylpyrid-3-yl; a compound of Formula (60) wherein R 3 is N(Me)Bu, Ar is 4 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Me)propargyl, Ar is 4 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Et)propargyl, Ar is 4 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is NHCH(CH 3 )CH(CH 3 )CH 3 , A r is 4 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N (CH2CH2θMe) - CH 2 CH=CH 2 , Ar is 4 , 6 -dimethylpyrid-3 -yl ; -52- a compound of Formula (60) wherein R 3 is N(CH CH 2 OMe)Me, r is 4 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(CH 2 CH 2 OMe)Et, A r is 4 , 6-dimethylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N(CH 2 CH 2 OMe)Pr, A r is 4 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N (CH 2 CH 2 OMe) - CH 2 cPr, Ar is 4 , 6-dimethylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is NHCH ( CH 3 ) CH 2 CH 3 , A r is 4 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is NHCH(cPr) 2 Ar is 4 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N (CH 2 CH 2 OMe) 2 , Ar is 4 , 6-dimethylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is NHCH(Et) 2 r is 4 , 6-dimethylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N(Et) 2 , Ar is 4 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is 2- ethylpiperid-1-yl, Ar is 2 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is cyclobutyl - 53 - amino, Ar is 2 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Me)CH 2 CH=CH 2 , Ar is 2 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Et)CH cPr, Ar is Ar is 2 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Pr)CH 2 cPr, Ar is Ar is 2 , 6-dimethylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N(Me)Pr, Ar is 2 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Me)Et, Ar is 2 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Me)Bu, Ar is 2 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Me ) propargyl, Ar is 2 , 6-dimethylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is NH(CH(CH 3 )CH(CH 3 )CH 3 , A r is 2 , 6-dimethylpyrid-3 - yi ; a compound of Formula (60) wherein R 3 is N (CH CH 2 OMe) - CH2CH=CH2, Ar is 2 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is • N(CH 2 CH 2 OMe)Me, A r is 2 , 6-dimethylpyrid-3 -yl ; -54- a compound of Formula (60) wherein R 3 is N(CH 2 CH 2 OMe)Et, A r is 2 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(CH 2 CH 2 OMe)Pr, Ar is 2 , 6-dimethylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N (CH2CH2θMe) - CH2cPr, Ar is 2 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is NH(CH ( CH 3 ) CH 2 CH 3 , A r is 2,6-dimethyl pyrid-3-yl; a compound of Formula (60) wherein R 3 is NHCH(cPr)2, Ar is 2,6-dimethyl pyrid-3 -yl; a compound of Formula (60) wherein R 3 is N (CH2CH2θMe) 2 , Ar is 2 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is NHCH(Et)2, Ar is 2 , 6-dimethyl -pyrid-3 -yl ; and a compound of Formula (60) wherein R 3 is N(Et) 2 , Ar is 2 , 6 -dimethyl -pyrid- 3 -yl . [3] Specifically preferred compounds of the present invention include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt forms thereof, wherein said compound is selected from the group: 4- ( (2 -butyl) amino) -2, 7 -dimethyl -8- (2 -methyl -4- -55- methoxyphenyl) - [1, 5-a] -pyrazolo- 1, 3 , 5-triazine; 4- ( (2-butyl) amino) -2, 7-dimethyl-8- (2, 5-di methyl -4- methoxyphenyl) - [1, 5-a] -pyrazolo-1, 3 , 5-triazine; 4- ( (3-pentyl) amino) -2 , 7-dimethyl-8- (2 , 5-dimethyl-4- methoxyphenyl ) - [1, 5-a] -pyrazolo- 1, 3 , 5-triazine; 4- ( (3-pentyl) amino) -2, 7-dimethyl-8- (2-methyl-4- methoxyphenyl) - [1 , 5-a] -pyrazolo-1, 3 , 5-triazine; 4- (N-cyclopropylmethyl-N-propylamino) -2 , 7-dimethyl - 8- (2 -methyl -4 -methoxyphenyl) - [1, 5-a] -pyrazolo- 1, 3,5- triazine ; 4- (N-cyclopropylmethyl-N-propylamino) -2 , 7-dimethyl - 8- (2 , 5 -dimethyl-4 -methoxyphenyl) - [1, 5-a] -pyrazolo- 1,3, 5-triazine; 4- (N-allyl-N- (2-methoxyethyl) amino) -2 , 7-dimethyl-8- (2 -methyl -4 -methoxyphenyl) - [1, 5-a] -pyrazolo- 1, 3,5- triazine; 4- ( N-allyl-N- (2-methoxyethyl) amino) -2 , 7-dimethyl-8- (2, 5 -dimethyl -4 -methoxyphenyl) - [1, 5-a] -pyrazolo- 1,3, 5 -triazine; 4- (diallylamino) -2, 7-dimethyl-8- (2 -methyl -4- methoxyphenyl) - [1, 5-a] -pyrazolo-1, 3 , 5-triazine; 4- (diallylamino) -2 , 7-dimethyl-8- (2 , 5-dimethyl-4- methoxyphenyl) - [1, 5-a] -pyrazolo-1, 3 , 5-triazine; 4- (N-ethyl-N- (2-methoxyethyl) amino) -2, 7-dimethyl-8 - (2 -methyl -4 -methoxyphenyl) - [1, 5-a] -pyrazolo- 1, 3,5- 56 - triazine; and 4- ( N-ethyl-N- (2-methoxyethyl) amino) -2 , 7-dimethyl-8- (2 , 5 -dimethyl -4 -methoxyphenyl) - [1, 5-a] -pyrazolo- 1, 3 , 5-triazine. [4] The present invention further provides compounds of Formula (70) X ^> "c83 FORMULA (70) and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt forms thereof selected from the group: a compound of Formula (70) wherein R is Cl , R 3 is - NHCH(n-Pr) 2 , R 4 is M e, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NHCH(CH 2 OMe) 2 , R 4 is Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - N ( CH 2 CH 2 OMe ) 2 , R 4a is Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; -57- a compound of Formula (70) wherein R is Cl , R 3 is -N(c- Pr) (CH 2 CH 2 CN) , R 4a is Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - N(CH 2 CH 2 OMe) 2 , R 4a i s Cl, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl, R 3 is - NHCH(CH 2 OMe) 2 , R 4a i s Cl , R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NHCH ( Et) 2 , R 4a is Cl, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - N ( Et ) 2 , R 4a is Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is -N(n- Pr) (CH 2 CH 2 CN), R 4 is M e, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is -N(n- Bu) (CH 2 CH 2 CN), R 4 is Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NHCH(n-Pr) (CH 2 OMe) , R 4a is Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NHCH ( Et ) 2 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NHCH ( CH 2 OMe ) 2 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is ( S) -58- NH(CH 2 CH 2 OMe)CH 2 OMe, R 4a i s Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl, R 3 is - NH(CH 2 CH 2 OMe)CH 2 OMe, R 4 is Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - N(CH 2 CH 2 OMe) 2 , R 4a i s Me, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl, R 3 is - NH ( Et), R 4a is Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NHCH(n-Pr) 2 , R 4a is Me, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NHCH(CH 2 OMe) 2 , R 4a is Me, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl, R 3 is ( S) - NH(CH 2 CH 2 OMe)CH 2 OMe, R 4a i s Me, R 4b is H, R 4c is Cl, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl, R 3 is - NH(CH 2 CH 2 OMe)CH 2 OMe, R 4a is M e, R 4b is H, R 4c is cl, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is -N(n- Pr) (CH 2 CH 2 CN), R 4 1S Me , R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - N ( Et ) 2 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl, R 3 is ( S) NH(CH 2 CH 2 OMe)CH 2 OMe, R 4a is cl, R 4b is H, R 4c is -59- Me , R 4 d is H and R 4 e is H ; a compound of Formula (70) wherein R is Cl , R 3 is - NH(CH 2 CH 2 OMe)CH 2 OMe, R 4 i s Cl, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - N ( Et) 2 , R 4a is Cl, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is -N(c- Pr) (CH 2 CH 2 CN), R 4 is M e , R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is -N(c- Pr) (CH 2 CH 2 CN), R 4a is cl , R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is -NHCH (n-Pr) (CH 2 0Me) , R 4a is M e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is -NHCH (n-Pr) (CH 2 OMe), R is C l , R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NHCH ( Et ) 2 , R 4a is Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (70) wherein R is Cl, R 3 is - NHCH ( Et ) 2 , R 4a is Br, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - N ( CH 2 CH 2 OMe ) 2 , R 4a is Br, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NHCH ( CH 2 OMe ) 2 , R 4a is Br, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; -60- a compound of Formula (70) wherein R is Cl , R 3 is - N ( Et ) 2 , R 4a is Me, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl, R 3 is - N ( Et ) 2 , R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is OMe and R ' 4e is H; a compound of Formula (70) wherein R is Cl, R 3 is - NHCH ( Et ) 2 , R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - N ( CH 2 CH 2 OMe ) 2, R 4 is Cl , R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NHCH ( CH 2 OMe ) 2 , R 4a is Cl , R 4b is H, R c is Cl, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - N(Pr) (CH 2 CH 2 CN) , R 4a is Cl , R 4b is H, R 4c is Cl, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - ■ N(Bu) (Et), R 4a i s cl, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl, R 3 is - NHCH (Et)CH 2 OMe, R 4a is cl, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NHCH ( Et ) 2 , R 4a is Cl, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl, R 3 is - NHCH ( Et ) 2 , R 4a is Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl, R 3 is -61- NHCH(Et ) 2 , R 4a 1S Cl, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NHCH ( Et) 2 , R 4a 1S Me, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - N NEEtt 22 ,, RR 44aa i 1 s S MMee,, :R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; and a compound of Formula (70) wherein R is Cl , R 3 is - N(Pr) (CH 2 CH 2 CN) , R 1S Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NHCH (n-Pr) 2 , R 4a ιg M e, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NHCH (CH 2 OMe) 2 , R 4 1S Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - N ( CH 2 CH 2 OMe ) 2 , R 4a is Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is -N(c- Pr) (CH 2 CH 2 CN) , R 4a 1S Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - N(CH 2 CH 2 OMe) 2 , R 4a 1S Cl , R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NHCH (CH 2 OMe) 2 , R 4a is Cl , R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (701 wherein R is Me, R 3 is - NHCH(Et) 2 , R 4 1S Cl, R 4b is H, R 4c is Me, R 4d is - 62 H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - N(Et) 2 , R 4a is Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is -N(n- Pr) (CH 2 CH 2 CN) , R 4a i s Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is -N(n- Bu) (CH 2 CH 2 CN) , R 4a i s Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NHCH(n-Pr) (CH 2 OMe) , R 4a is M e, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NHCH(Et) 2 , R 4a is M e , R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NHCH (CH 2 OMe) 2 , R a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is ( S) - NH(CH 2 CH 2 OMe)CH 2 OMe, R 4a is Me , R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NH(CH 2 CH 2 OMe)CH 2 OMe, R 4a is M e, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - N(CH 2 CH 2 OMe) 2 , R 4a is M e, R 4b ■ is H, R 4c is Cl, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NH(Et), R a i s Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; -63- a compound of Formula (70) wherein R is Me, R 3 is - NHCH ( n-Pr ) 2 , R 4a is Me, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NHCH(CH 2 OMe) 2 , R 4a is Me, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is (S) - NH(CH 2 CH 2 OMe)CH 2 OMe, R 4 is M e, R 4b is H, R 4c is Cl, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NH(CH 2 CH 2 OMe)CH 2 OMe, R 4a i s M e, R 4b is H, R 4c is Cl, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is -N(n- Pr) (CH 2 CH 2 CN), R 4 is M e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - N(Et) 2 , R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is ( S) - NH (CH 2 CH 2 OMe)CH 2 OMe, R 4a is Cl , R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NH(CH 2 CH 2 OMe)CH 2 OMe, R 4a is Cl , R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - N ( Et ) 2 , R 4a is Cl, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is -N(c- Pr) (CH 2 CH 2 CN) , R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is -N(c- -64- Pr) (CH 2 CH 2 CN) , R a 1S Cl, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is -NHCH (n-Pr) (CH 2 0Me), R a 1S Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is -NHCH (n-Pr) (CH 2 OMe), R 4a 1S C l , R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NHCH(Et) 2 , R 4a is Br, R 4b is H, R 4c is OMe, R 4d is OMe and R e is H; a compound of Formula (70) wherein R is Me, R 3 is - NHCH(Et) 2 , R 4 1S Br, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - N(CH 2 CH 2 OMe) 2 R 4a is Br, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NHCH(CH 2 OMe) 2 , R 4a s Br, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - N(Et) 2 , R 4a is Me, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is N(Et) 2 , R 4a is Cl, R 4b is H, R 4c is OMe, R 4d ι_ OMe and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is NHCH(Et)2, R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - N(CH 2 CH 2 OMe) 2 , R 4a is Cl, R 4 4 b b i,s„ „H, R„4 4 c c i .s„ rC.l, , π R4 ~ -d -65- is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NHCH ( CH 2 OMe ) 2 , R 4a is Cl, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - N(Pr) (CH 2 CH 2 CN) , R 4a is cl , R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - N ( Bu ) ( Et ) , R 4a is Cl, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NHCH (Et)CH 2 OMe, R 4a is cl , R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NHCH ( Et ) 2 , R 4a is Cl, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NHCH ( Et ) 2 , R 4a is Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is NHCH ( Et ) 2 , R 4a is Cl, R 4 4 b b is H, R , 4 4 c c is Me, ,4 I rd. H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NHCH(Et) 2 , R 4a is Me, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NEt 2 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; and a compound of Formula (70) wherein R is Me, R 3 is - N(Pr) (CH 2 CH 2 CN) , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; -66- a compound of Formula (70) wherein R is F, R 3 is - NHCH (n-Pr) 2 , R 4a i s Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH(CH 2 OMe) 2 , R is M e, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N ( CH 2 CH 2 OMe ) 2 , R 4a is Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is -N(c- Pr) (CH 2 CH 2 CN) , R 4a is M e, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N ( CH 2 CH 2 OMe ) 2 , R 4a is Cl , R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH ( CH 2 OMe ) 2 , R 4a is Cl , R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH ( Et ) 2 , R 4a is Cl, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N ( Et ) 2 , R 4a is Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is -N(n- Pr) (CH 2 CH 2 CN) , R 4a is M e, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is -N(n- Bu) (CH 2 CH 2 CN) , R 4a i s Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - -67- NHCH(n-Pr) (CH 2 OMe) , R 4a is Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH ( Et ) 2 , R a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH ( CH 2 OMe ) 2 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is ( S) - NH(CH 2 CH 2 OMe)CH 2 OMe, R 4a is Me, R 4b is H, R 4c is Me, R ,4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NH(CH 2 CH 2 OMe)CH 2 OMe, R 4a is Me , R 4b i s H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N(CH 2 CH 2 OMe) 2 , R 4a is M e, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NH ( Et ) , R 4a is Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH (n-Pr) 2 , R 4a is Me , R 4b is H, R 4c is Cl, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH(CH 2 OMe) 2 , R 4a is Me, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is ( S) NH(CH 2 CH 2 OMe)CH 2 OMe, R a is M e, R 4b is H, R 4c is Cl, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NH(CH 2 CH20Me)CH20Me, R 4a is Me, R 4b is H, R 4c is -68- Cl , R 4 d is H and R 4 e i s H ; a compound of Formula (70) wherein R is F, R 3 is -N(n- Pr) (CH 2 CH 2 CN) , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N(Et) 2 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is ( S) - NH(CH 2 CH 2 OMe)CH 2 OMe, R 4a is C l, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NH(CH 2 CH 2 OMe)CH 2 OMe, R 4a is C l , R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N(Et ) 2 , R 4a is Cl, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is -N(c- Pr) (CH 2 CH 2 CN) , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is -N(c- Pr) (CH 2 CH 2 CN) , R 4a 1S Cl, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is -NHCH (n-Pr) (CH 2 OMe), R 4a 1S Me , R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is -NHCH (n-Pr) (CH 2 OMe) , R 4a ls cl, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH(Et) 2 , R 4a is Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; -69- a compound of Formula (70) wherein R is F, R 3 is - NHCH(Et) 2 , R 4a is Br, R 4b is H, R 4c is OMe, R 4d H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N ( CH 2 CH 2 OMe ) 2 , R 4a is Br, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH(CH 2 OMe) 2 , R 4a is B r, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N ( Et ) 2 , R 4a is Me, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N ( Et ) 2 , R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH ( Et) 2 , R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N(CH 2 CH 2 OMe) 2 , R 4 is C l, R 4 4 b b i•s „H, R n 4 4 c c i,s„ ,C-,l-, , π R4-d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH(CH 2 OMe) 2 , R 4 is cl , R 4 4 b b i■ „s THT, rR,4 4 C c i•s„ r C-l , π R-d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N(Pr) (CH 2 CH 2 CN) , R 4a is C l , R 4b is H, R 4c is Cl, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N(Bu) ( Et), R is Cl, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; -70- a compound of Formula (70) wherein R is F, R 3 is - NHCH(Et)CH 2 OMe, R 4a is cl , R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH(Et ) 2 , R 4a is Cl, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH ( Et ) 2 , R 4a is Me, R 4b is H, R 4c is Me, R 4d is H .and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH ( Et ) 2 , R 4a is Cl, R 4 4 b b is„ „H, -R,4 4 c c ijs f. M ΆΛ e„, π R4-d H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is NHCH ( Et ) 2 , R 4a is Me, R 4b is H, R 4c is Cl , R -4 4 H d i.-ss H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is -NEt 2 R R 44aa iiss MMee,, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; and a compound of Formula (70) wherein R is F, R 3 is - N(Pr) (CH 2 CH 2 CN), R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - N(Pr) (CH 2 CH 2 OMe) , R a is M e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - N(Et) (CH 2 CH 2 OMe) , R 4a i s Me, R 4b is H, R 4c is OMe, 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl, R 3 is - N(Me) (CH 2 CH 2 OMe) , R 4a is M e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NMeEt, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H -71- and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NMePr, R 4 is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl, R 3 is - NMeBu, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl, R 3 is -NH- 2 -butyl, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl, R 3 is cyclobutylamino, R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - N(Pr) (CH 2 CH 2 OMe) , R 4a is M e, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - N(Et) (CH 2 CH 2 OMe) , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - N(Me) (CH 2 CH 2 OMe), R 4a is Me, R 4b is H, R 4c is OMe, ,4d is Me and R 4e .s H; a compound of Formula (70) wherein R is Cl , R 3 is - NMeEt, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is Cl, R 3 is - NMePr, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NMeBu, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me -72- and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is -NH- 2 -butyl, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is cyclobutylamino, R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is ME and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N(Pr) (CH 2 CH 2 OMe) , R 4a is M e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N(Et) (CH 2 CH 2 OMe) , R 4a is M e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N(Me) (CH 2 CH 2 OMe) , R 4a is M e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NMeEt, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NMePr, R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NMeBu, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein ' R is F, R 3 is -NH- butyl, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is cyclobutylamino, R 4a 1 S Me, R 4b is H, R 4c is OMe, -73- R 4 d i s H and R 4 e i s H ; a compound of Formula (70) wherein R is F, R 3 is - N(Pr) (CH 2 CH 2 OMe) , R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N(Et) (CH 2 CH 2 OMe) , R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N(Me) (CH 2 CH 2 OMe) , R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NMeEt, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NMePr, R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NMeBu, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is -NH-2- butyl, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is cyclobutylamino, R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - N(Pr) (CH 2 CH 2 OMe) , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - N(Et) (CH 2 CH 2 OMe), R 4a 1S Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; -74- a compound of Formula (70) wherein R is Me, R 3 is - N(Me) (CH 2 CH 2 OMe) , R 4a is M e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 i NMeEt, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 i .sι - NMePr, R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NMeBu, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is -NH- 2 -butyl, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is cyclobutylamino, R 4a is Me> R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - N(Pr) (CH 2 CH 2 OMe) , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - N(Et) (CH 2 CH 2 OMe) , R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - N(Me) (CH 2 CH 2 OMe) , R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NMeEt, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; -75- a compound of Formula (70) wherein R is Me, R 3 is - NMePr, 4a i s Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NMeBu, R 4a ig Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is -NH- 2 -butyl, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; and a compound of Formula (70) wherein R is Me, R 3 is cyclobutylamino, R 4a i s M e, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H. [5] Specifically preferred compounds of the present invention include compounds and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt forms thereof, wherein said compound is selected from: 7- (diethylamino) -2 , 5-dimethyl-3 - (2 -methyl -4 -methoxyphenyl- [1,5-a] -pyrazolopyrimidine and 7- (N- (3 -cyanopropyl) -N-propylamino) -2 , 5- dimethyl-3- (2 , 4-dimethylphenyl) - [1, 5-a] - pyrazolopyrimidine . [6] The present invention also provides pharmaceutical compositions comprising a therapeutically effective amount of the above- described compounds and a pharmaceutically acceptable carrier. [7] The present invention still further provides methods of treating affective disorder, anxiety, depression, headache, irritable bowel syndrome, post- - 76 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 the above-described compounds. Many compounds of this invention have one or more asymmetric centers or planes. Unless otherwise indicated, all chiral (enantiomeric and diastereomeric) and racemic forms are included in the present invention. Many geometric isomers of olefins, C=N double bonds, and the like can also be present in the compounds, and all such stable isomers are contemplated in the present invention. The compounds may be isolated in optically active or racemic forms. It is well known in the art how to prepare optically active forms, such as by resolution of racemic forms or by synthesis from optically active starting materials. All chiral, (enantiomeric and diastereomeric) and racemic forms and all geometric isomeric forms of a structure are intended, unless the specific stereochemistry or isoraer form is specifically indicated. The term "alkyl" includes both branched and straight -chain alkyl having the specified number of -77- carbon atoms. Commonly used abbreviations have the following meanings: Me is methyl, Et is ethyl, Pr is propyl, Bu is butyl. The prefix "n" means a straight chain alkyl. The prefix "c" means a cycloalkyl. The prefix " ( S) " means the S enantiomer and the prefix " (R) " means the R enantiomer. Alkenyl" includes hydrocarbon chains of either a straight or branched configuration and one or more unsaturated carbon-carbon bonds which may occur in any stable point along the chain, such as ethenyl, propenyl, and the 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 atoms, 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 -78- 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 benzyloxycarbonyls, 1- (p- biphenyl) -1-methylethoxycarbonyl , 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 -79- acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. Pharmaceutically acceptable salts of the compounds of the invention can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two; generally, nonaqueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. Lists of suitable salts are found in Remington 1 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 -80- effective to antagonize abnormal level of CRF or treat the symptoms of affective disorder, anxiety or depression in a host. Syntheses Some compounds of Formula (1) may be prepared from intermediate compounds of Formula (7) , using the procedures outlined in Scheme 1: SCHEME 1 agent or *' sulfonylating agent + / - base, + / - Ar (8) R 3 H, + / - + / - solvent Ar (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 -80°C to 250°C to give products of Formula (8) (where X is halogen, alkanesulfonyloxy, -81- arylsulfonyloxy or haloalkane-sulfonyloxy) . Halogenating agents include, but are not limited to, S0C1 2 , POCI 3 , PCI 3 , PCI 5 , POBr 3 , PBr 3 or PBr 5 . 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) , 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 -20°C to 100°C. Compounds of Formula (8) may be reacted with compounds of Formula R 3 H (where R 3 is defined as above except R 3 is not SH, COR 7 , C0 2 R 7 , aryl or heteroaryl) -82- in the presence or absence of a base in the presence or absence of an inert solvent at reaction temperatures ranging from -80 to 250°C 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) , 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 0°C to 140°C Scheme 2 delineates the procedures for converting intermediate compounds of Formula (7) (where Y is S) to some compounds of Formula (1) . -83- SCHEME 2 SR 13 R 13 X , + / - base , + / - solvent N ^ _r" N N Ar Ar (7) Y = S (12) oxidizing agent, solvent R 3 H, + / - base, + / - solvent S (O) R 3 H , + / - base + / - solvent Ar Ar (13) (1 ) A = N Compounds of Formula (7) where Y is S) may be treated with an alkylating agent R 13 X (where R 13 is defined as above, except R 13 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 -80°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 hydroxides, alkali metal bis (trialkylsilyl) amides (preferably -84- 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), 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 -80°C to 100°C Compounds of Formula (12) (Formula (1) where R 3 is SR 13 ) may then be reacted with compounds of Formula R 3 H 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 R 3 is SR 13 ) may be oxidized to compounds of Formula (13) (Formula (1) where R 3 is S(0) n R 13 ' n is 1,2) by treatment with an oxidizing agent in the presence of an inert solvent at temperatures ranging from -80°C to 250°C 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 carbons, preferably acetone), water, alkyl -85- alcohols (1 to 6 carbons) , 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 R 3 is S(0) n R 13 ' n is 1,2) may then be reacted with compounds of Formula R 3 H 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 R 3 may be - NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , -NR 8 C02R 13 , -NR 6 R 7 ' - NR 8 S0 2 R 7 , may be prepared from compounds of Formula (7) , where Y is NH, by the procedures depicted in Scheme 3. -86- SCHEME 3 Y *3 alkylating, sulfonylating N v HN A " N ' t X 1 Ar (7) Y = NH A = N; R 3 = NR 6 R 7 ,NR 8 COR 7 , N(COR 7 ) 2 , NRgCONR^ 7 NRβC0 2 R 13 Reaction of compounds of Formula (7) , where Y is NH, 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 -80°C to 250°C may afford compounds of Formula (1), where R 3 may be -NR 8 COR 7 , -N(COR 7 ) 2 , - NR 8 CONR 6 R 7 , -NR 8 Cθ2R 13 , -NR 6 R 7 ' -NR 8 S0 2 R 7 . Alkylating agents may include, but are not limited to, Ci-Cio alkyl -halides, -tosylates, -mesylates or -triflates; i-Cio haloalkyld - 10 halogens) -halides, -tosylates, -mesylates or -triflates; C2-C8 alkoxyalkyl -halides, - tosylates, -mesylates or -triflates; C 3 -C6 cycloalkyl - halides, -tosylates, -mesylates or -triflates; C4- C12 cycloalkylalkyl -halides, -tosylates, -mesylates or -triflates; aryl (C1-C 4 alkyl) -halides, -tosylates, - mesylates or -triflates; heteroaryl (C1-C4 alkyl) - halides, -tosylates, -mesylates or -triflates; or heterocyclyl (C1-C4 alkyl) -halides, -tosylates, - 17- mesylates or -triflates. Acylating agents may include, but are not limited to, Ci-Cio alkanoyl halides or anhydrides, Cι-Cχo haloalkanoyl halides or anhydrides with 1 - 10 halogens, C2-C8 alkoxyalkanoyl halides or anhydrides, C -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, 1-C10 alkylsulfonyl halides or anhydrides, Cχ-Cιo haloalkylsulfonyl halides or anhydrides with 1 - 10 halogens, C 2 -Cs alkoxyalkylsulfonyl halides or anhydrides, C 3 -Cς cycloalkylsulfonyl halides or anhydrides, C4-Cχ 2 cycloalkylalkylsulfonyl halides or anhydrides, arylsulfonyl halides or anhydrides, aryl(Cχ-C4 alkyl)-, heteroarylsulfonyl halides or anhydrides, heteroaryl (C1-C4 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 (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) mide) , 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) , 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 0°C to 100°C Scheme 4 delineates procedures, which may be employed to prepare intermediate compounds of Formula (7), where Y is 0, S and Z is CR 2 . -89- SCHEME 4 R 2 COR b , base , NH 2 NH 2 - H2O , solvent __ solvent ArCH 2 CN R2 Ar (3) NH l' A ( 5 ) ^ O c -N NH HN ' + / - acid, solvent (4) Ar - y , y V ■ R2 Ar (6) y=c (R d ) 2 , base , HN solvent T * * J \ Ar (7) Y = 0 , S ; Z = CR 2 Compounds of the formula ArCH 2 CN are reacted with compounds of the formula R 2 C0R b , where R 2 is defined above and R b 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 -90- 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) , 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) . Preferred reaction temperatures range from 0°C to 100°C. Compounds of Formula (3) may be treated with hydrazine-hydrate in the presence of an inert solvent at temperatures ranging from 0°C to 200°C, preferably 70°C to 150°C, 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 R c is alkyl (1-6 carbons) ) in the -91- presence or absence of an acid in the presence of an inert solvent at temperatures ranging from 0°C to 200°C 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) , 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 100°C. Compounds of Formula (6) may be converted to intermediate compounds of Formula (7) by treatment with compounds C=Y(R d ) 2 (where Y is 0 or S and R d 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 200°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) , alkali metal carbonates, alkali metal hydroxides, trialkyl amines (preferably N,N-di- isopropyl-N-ethyl amine or triethylamine) or aromatic amines (preferably pyridine) . Inert solvents may -92- 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 N-methylpyrrolidin-2-one) , dialkylsulfoxides (preferably dimethylsulfoxide) or aromatic hydrocarbons (preferably benzene or toluene) . Preferred temperatures are 0°C to 150°C. Intermediate compounds of Formula (7) , where Z is N, may be synthesized according the methods outlined in Scheme 5. -93- SCHEME 5 Rq ^ N N^ N R < -CH 2 N 3 , base , reducing agent solvent solvent ► ArCH 2 CN Ar ( 9) NH (5) °* c + / - acid, solvent H,N (10) Ar (11) HN Y-=C(R d ) 2 . base, A N^ solvent^ N Ar (7) Y = O, S; Z =N Compounds of ArCH 2 CN are reacted with compounds of Formula RSCH 2 N 3 (where R3 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 .94. 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 carbons, preferably acetonitrile) , dialkyl ethers (preferably diethyl ether) , cyclic ethers (preferably tetrahydrofuran or 1, 4-dioxane) , N,N-dialkylformamides (preferably dimethylformamide) , 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 ambient temperature to 100°C. Compounds of Formula (9) may be treated with a reducing agent in an inert solvent at -100°C to 100°C 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-on-carbon, Ptθ 2 , Pt-on- carbon, Rh-on-alumina or Raney nickel, (b) alkali metals (preferably sodium) in combination with liquid ammonia or (c) eerie 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 -95- 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 60°C 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 (7) (where Z is CR 2 ) . Compounds of Formula (1) may also be prepared from compounds of Formula (7) (where Y is 0, S and Z is defined above) as outlined in Scheme 6: SCHEME 6 R 3 H, + / - acid, + / - dehydrating + / - solvent Ar Ar (7) Y = O, S; Z = N, CR 2 (1) A = N Compounds of Formula (7) may be reacted with compounds of Formula R 3 H in the presence of a dehydrating agent in an inert solvent at reaction temperatures ranging from 0°C to 250°C. Dehydrating agents include, but are not limited to, P 2 O 5 , molecular sieves or inorganic or organic acids. Acids may include, but are not limited to alkanoic acids of 2 to 10 carbons (preferably acetic - 96 - 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. 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 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 150°C. Some compounds of Formula (1) (where A is N) may also be prepared by the methods shown in Scheme 7: SCHEME 7 R 3 C (OR θ ) 3 , N NH HN' + / - acid solvent H Ar (14) Ar (1) A = N Intermediate compounds of Formula (14) , where Z is defined above, may be reacted with compounds of Formula R 3 C(OR e )3, where R e may be alkyl (1 to 6 carbons) in the presence or absence of an acid in an inert solvent at temperatures ranging from 0°C to 250°C Acids may 97 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 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 50°C to 150°C. Intermediate compounds of Formula (7) may also be synthesized by the reactions displayed in Scheme 8. SCHEME 8 ArM, + / - 2 solvent 15) Y = OH, SH NR 6 R 7 ; Ar Z = N, CR 2 , (7) A = N X = Br, Cl, I, B(OR"")2 - 98 - Compounds of Formula (15) , (where Y is OH, SH, NR 6 R 7 ; Z is defined above, X is Br, Cl , I, O 3 SCF 3 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, Znl, MgBr, MgCl , Mgl, CeCl 2 , CeBr 2 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. Organometallic catalysts include, but are not limited to, palladium phosphine complexes (such as Pd(PPh 3 ) 4 ), palladium halides or alkanoates (such as PdCl 2 (PPh 3 )2 or Pd(OAc) 2 ) or nickel complexes (such as NiCl 2 (PPh 3 ) 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, 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 water. Preferred reaction temperatures range from -80°C to 100°C 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 Organic Synthesis, Trost, B.M. ed. , (Elmsford, NY: Pergamon - 99 Press, 1991), 1, 211-230; Knight, D.W., Coupling Reactions between sp 2 Carbon Centers, in Comprehensive Organic 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. SCHEME 9 A ? ArM, + / - catalyst, solvent N Ar (16) X = Br, Cl, I, (1) B(OR"")2, O3SCF3 Compounds of Formula (16) , where A, Z, R 1 and R 3 are defined above and X is Br, Cl , I, O 3 SCF 3 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, Znl, MgBr, MgCl, Mgl, CeCl 2 , CeBr 2 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(PPh 3 ) ), palladium halides or alkanoates (such as PdCl 2 (PPh 3 ) 2 or Pd(OAc) 2 ) or nickel complexes (such as NiCl 2 (PPt- 3 ) 2 ) • Bases may include, but are not limited to, alkali metal carbonates or trialkyl amines 100 - (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, 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 water. Preferred reaction temperatures range from -80°C to 100°C Intermediate compounds of Formula (7) (where Y is O, S, NH, Z is CR 2 and R 1 , R 2 and Ar are defined as above) may be prepared as illustrated in Scheme 10. SCHEME 10 NH 2 NH 2 (C=Y)NH 2 HN NC. + / - base or acid, solvent Ar (3) (17) + I - acid, solvent Ar (7) Y = O, S, NH; Z = CR 2 Compounds of Formula (3) may be reacted with compounds 101 of Formula H 2 NNH (C=Y) NH 2 , where Y is 0, S or NH, in the presence or absence of a base or acid in an inert solvent at temperatures from 0°C 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) , 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, 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 0°C to 150°C. Compounds of Formula (17) may then be reacted with compounds of Formula R 3 C(0R e )3, where R e may be - 102 - alkyl (1 to 6 carbons) in the presence or absence of an acid in an inert solvent at temperatures ranging from 0°C to 250°C. 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 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 50°C to 150°C. In Scheme 11, the procedures which may be used to convert compounds of Formula (1) , where R 3 is COR 7 , C0 2 R 7 , NR 8 COR 7 and CONR 6 R 7 , to other compounds of Formula (1), where R 3 is CH(OH)R 7 , CH 2 OH, NR 8 CH 2 R 7 and CH 2 NR S R 7 by treatment with a reducing agent in an inert solvent at temperatures ranging from -80°C to 250°C - 103 SCHEME 11 reducing agent, solvent Ar (1) R 3 = COR 7 , C0 2 R 7 , (1) R |3 J ^ = C(OH)R' CONR 6 R 7 CH 2 OH , CH 2 NR 6 R 7 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) , 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 R 3 is COR 7 or CO 2 R 7 , to other compounds of Formula (1) , where R 3 is C(0H) (R 7 ) 2 by treatment with a reagent of Formula R 7 M in an inert solvent at temperatures ranging from -80°C to 250°C. -104- SCHEME 12 y^< -N N ^ reducing agent, solvent Ar Ar (1) R 3 = COR 7 , CO.R' (1) R 3 = C(OH) (R 7 ) M is halogen, alkali metal, ZnCl, ZnBr, Znl, MgBr, MgCl, Mgl, CeCl 2 . CeBr 2 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 R 3 may be - NR 8 COR 7 , -N(COR 7 ) 2. -NR 8 CONR 6 R 7 , -NR 8 C0 R 13 , -NR 6 R 7 ' - NR 8 S0 2 R 7 , may be synthesized as depicted in Scheme 13. - 105 - SCHEME 13 NC. NH, (18) + / - base, solvent ιl- Ar (19) Ar (4) Z = CR 2 (10) Z = N alkylating, or acylating agents + / - base, solvent Ar ( 1 ) A = CR R 3 =NR 6 R 7 , NR 8 COR 7 , N (COR 7 ) 2 , NR 8 CONR 6 R 7 , NR 8 C0 2 R 13 Reaction of compounds of Formula (18) , where R and R 1 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 106 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) , 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 0°C to 100°C. 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 - 80°C to 250°C may afford compounds of Formula (1) , where R 3 may be -NR 8 COR 7 , -N(COR 7 ) 2 , -NR 8 CONR 6 R 7 , - NR 8 C0 2 R 13 , -NR 6 R 7 ' -NR 8 S0 2 R 7 . Alkylating agents may include, but are not limited to, Cχ-Cιo alkyl -halides, -tosylates, -mesylates or -triflates; Ci-Cio haloalkyld - 10 halogens) -halides, -tosylates, - -107- mesylates or -triflates; C 2 -Cs alkoxyalkyl -halides, - tosylates, -mesylates or -triflates; C 3 -C6 cycloalkyl- halides, -tosylates, -mesylates or -triflates; C4- Cχ 2 cycloalkylalkyl -halides, -tosylates, -mesylates or -triflates; aryl(Cι-C4 alkyl) -halides, -tosylates, - mesylates or -triflates; heteroaryl (C3 . -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, Cχ-Cιo alkanoyl halides or anhydrides, C1-C10 haloalkanoyl halides or anhydrides with 1 - 10 halogens, C 2 -Cs alkoxyalkanoyl halides or anhydrides, C 3 -Cg cycloalkanoyl halides or anhydrides, C 4-Cι 2 cycloalkylalkanoyl halides or anhydrides, aroyl halides or anhydrides, aryl(Cχ-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, c l _ ιo alkylsulfonyl halides or anhydrides, C1-C10 haloalkylsulfonyl halides or anhydrides with 1 - 10 halogens, C -Cs alkoxyalkylsulfonyl halides or anhydrides, C 3 -Cg cycloalkylsulfonyl halides or anhydrides, C4-Cτ_ cycloalkylalkylsulfonyl halides or anhydrides, arylsulfonyl halides or anhydrides, aryl(C_-C4 alkyl)-, heteroarylsulfonyl halides or anhydrides, heteroaryl (C1-C4 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 (1 to 6 carbons) (preferably 108 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) , 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 0°C to 100°C Compounds of Formula (1) , where A is CR and R is defined above, may be synthesized by the methods depicted in Scheme 14. 109 - SCHEME 14 y& HN ^ % 1 z R X** * / (20) H,N- ^ \ + / - base, Ar solvent -^ (4 ) Z = CR 2 (10) Z = N (1) Ar A = CR R θ O- R 3 H, + / - base, R + / - solvent (21) + / - base , solvent OH ._.__ ^ -N halogenating agent N or sulf S onyl,a,t.i-n,g agent N- + / - base, + / - solvent N Ar Ar (22) (23) Compounds of Formula (4) or (10) may be treated with compounds of Formula (20) , where R 1 and R 3 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 •110- 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 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) , 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 0°C to 100°C 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 R 1 is defined above and R e is alkyl (1 - 6 carbons), 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) , - Ill - 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) , 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 0°C to 100°C. 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 250°C to give products of Formula (23) (where X is halogen, alkanesulfonyloxy, arylsulfonyloxy or haloalkane-sul onyloxy) . Halogenating agents include, but are not limited to, S0C1 2 , P0C1 3 , PCI 3 , PCI 5 , POBr 3 , PBr 3 or PBr 5 . 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 -112- 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) , 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 -20°C to 100°C Compounds of Formula (23) may be reacted with compounds of Formula R 3 H (where R3 is defined as above except R 3 is not SH, COR 7 , C0 2 R 7 , 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 250°C 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 - 113 - (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) , 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 0°C to 140°C Some compounds of Formula (1) may also be prepared using the methods shown in Scheme 15. - 114 R O NH 2 NH 2 , + / - acid, - acid, solvent X H .N H N OH Ar H 2 (25) Ar (26)Y = O, For A = N : For A = CR: 1) R 1 C(=NH)OR β 1) R 1 (C=0)CHR(C=Y)0R o +/- acid, solvent +/- base or acid, 2) Y=C(Rd) 2 solvent +/- base, solvent R C(0Rc) 3 +/- solvent see text A compound of Formula (24) (R c 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 -115- R X C (=NH)OR e , where R 1 is defined above and R e 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(R d )2 (where Y is 0 or S and R d 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 R 1 (C=0) CHR(C=Y)OR c (where R 1 and R are defined as above and R c 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 solvent, followed by reaction with R 3 H or R 2 H in the presence or absence of a base in an inert solvent to give compounds of Formula (1) (where Z is CR 2 ) . It will be recognized by chose skilled in the art that various combinations of halogenating agents, sulfonylating agents, R 3 H or R 2 H 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 R 2 H (or R 3 H) , then repeat the reaction with halogenating agents or sulfonylating agents and react with R 3 H (or R 2 H) to •116- 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 R f X (where R f 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 R 3 H 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 NH 2 NH (C=NH) NH 2 in the presence or absence of an acid in an inert solvent, followed by reaction with compounds R 1 C(OR c ) 3 (where R c is lower alkyl and R 1 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. 117 SCHEME 16 YH R 14 R 1 X, +/- base N solvent see text .N N" I ^ / R l ' Ar (1) Z = COH Compounds of Formula (27b) may be treated with various alkylating agents R 14 X (where R 14 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 R 3 H in the presence or absence of a base in an inert solvent to give 118 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 R f X (where R f 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 R 3 H 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 R 14 X (where R 14 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 COR 7 . 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 hydrides, alkali metal dialkylamides (preferably lithium di-isopropylamide) , alkali metal bis (trialkylsilyl) amides (preferably -119- 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, -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 -20°C to 100°C 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 (δ) 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 (Cl) with NH 3 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 - 120 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 0, Ri is CH 3 , Z is C-CH 3 , 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 2,4- dimethylphenylacetonitrile (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 IN HCl solution was added until the pH = 5-6. The mixture was extracted with ethyl acetate (3 X 200 mL) ; - 121 - the combined organic layers were dried over MgS0 4 and filtered. Solvent was removed in vacuo to afford a white solid (45.7g, 74% yield): NMR (CDC1 3 ,300 MHz) : ; CI-MS: 188 (M + H) . B. 5-Amino-4- (2 , 4-dimethylphenyl) -3-methylpyrazole A mixture of 1-cyano-l- (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 HC1 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 MgS0 4 and filtered. Solvent was removed in vacuo to give a pale brown viscous oil (34.6g, 75% yield) : NMR (CDC1 3 ,300 MHz): 7.10 (s, 1H) , 7.05 (d, 2H, J=l), 2.37 (s, 3H) , 2.10 (s, 3H) ; CI-MS: 202 (M + H) . C 5-Acetamidino-4- (2 , 4-dimethylphenyl) -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 MgS0 4 and filtered. Solvent was removed by simple distillation and the pot residue, a •122- 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) -3- methylpyrazole ( 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, 61% yield): NMR (DMSO-d 6 ,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 , 4- dimethylphenyl) -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 IN HCl solution was added slowly until pH = 5-6. The aqueous layer was extracted with ethyl acetate three times; the combined organic layers were dried over MgS0 4 and filtered. Solvent was removed in vacuo to give a pale tan solid (26g, 98% yield) : NMR (CDC1 3 ,300 MHz) : 7.15(s, 1H) , 7.09 (s, 2H) , 2.45 (s, 3H) , 2.39 (S, 3H) , 2.30 (s, 3H) ; CI-MS: 269 (M + H) . - 123 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 0, R__ is CH 3 , Z is N, Ar is 2 , 4 , 6-trimethylphenyl) A. 1 -Phenylmethyl -4 - (2,4,6-1rimethylphenyl ) -5- aminotriazole A mixture of 2 , 4 , 6-trimethylbenzyl cyanide (l.Og, 6.3 mmol), 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 MgS0 4 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 (CDC1 3 ,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- phenylmethyl -4- (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 HC1 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 - 124 - combined organic layers were dried over MgS0 4 and filtered. Solvent was removed in vacuo to give a yellow solid (520 mg) , which was homogeneous by thin layer chromatography (ethyl acetate) : NMR (CDC1 3 ,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) -5- aminotriazole (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-d 6 , 300 MHz) :7.90-7.70 (br s, 0.5H) , 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 reacted, 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 hours, then cooled to room temperature. The reaction mixture was diluted with water; a IN HCl solution was added until pH = 5-6 and three extractions with ethyl acetate were performed. 125 - The combined organic layers were dried over MgS0 4 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 (CDC1 3 ,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 R 3 is CH (CHC0 2 CH 3 ) 2 , Ri is CH 3 , Z is C-CH 3 , 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 , 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 MgS0 4 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, 68% yield): NMR (CDC1 3 ,300 MHz): 7.55 (d, 1H, J = 1) , 7.38 (dd, 1H, J = 7,1 ), 7.30 (d, 1H, J = 7), 2.68 (S, 3H) , 2.45 (s, 3H) ; CI-MS: 327 (M + H) . 126 B. 4- (di (carbomethoxy) methyl) -2, 7-dimethyl-8- (2,4- dimethylphenyl) [1,5-a] -pyrazolo- 1, 3, 5-triazine Sodium hydride (60% 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 MgS0 4 and filtered. Solvent was removed in vacuo to give a brown oil. Column chromatography (ethyl acetate : hexanes :: 1 : 9) afforded, after removal of solvent in vacuo, a pale yellow solid (Rf = 0.2, 250 mg, 35% yield): mp 50-52°C; NMR (CDC1 3 , 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 = 7) , 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 R 3 is NHCH (CH 2 OCH 3 ) 2 , Ri is CH 3 , Z is C-CH 3 , Ar is 2 , 4-dichlorophenyl) 127 A. 4-chloro-2, 7-dimethyl-8- (2 , 4-dichlorophenyl) [1,5- a] - 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 MgS0 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, 68% yield): NMR (CDC1 3 ,300 MHz) : 7.55 (d, 1H, J = 1) , 7.38 (dd, 1H, J = 7,1 ) , 7.30 (d, 1H, J = 7) , 2.68 (s, 3H) , 2.45 (s, 3H) ; CI-MS: 327 (M + H) . B. 4- (1, 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 , 4- dichlorophenyl) [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 MgS0 4 and filtered. Solvent was removed in vacuo . Column chromatography (CH 2 C1 2 :CH 3 OH: : 50 : 1) afforded one fraction. Removal of solvent in vacuo gave a solid (250 mg, 35% yield) : mp 118-120°C; NMR (CDC1 3 ,300 MHz): 7.50 (s, 1H) , 7.28 (dd, 2H, J = 8,1), -128- 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 C 18 H 2 iCl 2 N 5 θ 2 : 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. 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 1 Ex. 3 Ar mp (°c) C-Me NHCH (CH2OMe) 2 2,4-Cl 2 -Ph 118-120 391bz C-Me N(CH 2 CH 2 OMe ) 2 2-Me-4,6- (MeO)2Ph oil -129- 395 bu C-Me NE 2 2 -Me-4 , 6 - (MeO) 2 P 114 396 bv C-Me NH- 3 -pentyl 2 -Me-4 , 6 - (MeO) 2 P 145 - 146 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. bu) Analysis Calcd: C 65.90, H: 7.72, N, 18.27; Found: C: 65.77, H 7.62, N: 18.26. bv) Analysis Calcd: C 65.02, H: 7.38, N, 18.96; Found: C: 65.01, H 7.43, N: 18.68. bz) CI-HRMS: Calcd: 430.2454; Found: 430.2468 (M + H) ; EXAMPLE 431 Preparation of 2 , 4 , 7-dimethyl-8- (4-methoxy-2- methylphenyl ) [1 , 5-a] -pyrazolo-1 , 3 , 5-triazine (Formula 1, where R 3 is CH 3 , R x is CH 3 , Z is C-CH 3 , Ar is 2 , 4-dimethylphenyl) 5-Acetamidino-4- (4-methoxy-2-methylphenyl) -3- methylpyrazole, acetic acid salt ( 602 mg, 2 mmol) was mixed with a saturated NaHC0 3 solution (10 mL) . The aqueous mixture was extracted with EtOAc three times. The combined organic layers were dried over MgS04 , 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 •130- mixture was concentrated in vacuo to give an oily solid. Column chromatography (CHC1 3 :MeOH: : 9 : 1) afforded, after removal of solvent in vacuo, a yellow viscous oil (Rf = 0.6, 210 mg, 37% yield): NMR (CDCI3, 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-methylphenyl) pyrazolo [1, 5-a] pyrimidine (Formula 1 where A is CH, Rl is Me, R3 is OH, Z is C-Me, Ar is 2-chloro-4-methylphenyl) 5-Amino-4- (2-chloro-4-methylphenyl) -3- methylpyrazole (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 hours, 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 (CDCI3, 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) ; CI-MS: 288 (M+H) . EXAMPLE 433 7-chloro-5-methyl-3- (2-chloro- 4-methylphenyl) pyrazolo [1, 5-a] pyrimidine •131- (Formula 1 where A is CH, Rl is Me, R3 is Cl , 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 hours, 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 [1, 5-a] pyrimidine (900 mg, 84% yield) as a yellow oil: NMR (CDC1 3 , 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) ; Cl- MS: 306 (M+H) . EXAMPLE 434 7- (pentyl-3-amino) -5 -methyl -3- (2-chloro- 4 -methylphenyl) pyrazolo [1, 5-a] pyrimidine (Formula 1 where A is CH, Rl is Me, R3 is pentyl-3- amino, Z is C-Me, Ar is 2 -chloro-4 -methylphenyl) A solution of 3-pentylamine (394mg, 6.5 mmol) and 7-chloro-5-methyl-3- (2-chloro-4- methylphenyl) 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 MgS04 , filtration and removal of solvent in vacuo produced a yellow solid. Flash chromatography (EtOAc : hexanes :: 1 :4) afforded a white - 132 - solid (140 mg, 60% yield) : mp 139-141°C; NMR (CDCI3, 300Hz):7.32 (s, IH) , 7.27 (d, IH, J = 8), 7.12 (d, IH, J = 7), 6.02 (d, IH, J = 9), 5.78 ( s, IH) , 3.50-3.39 (m, IH) , 2.45 (s, 3H) , 2.36 (s, 6H) , 1.82-1.60 (m, 4H) , 1.01 (t, 6H, J = 8); Analysis Calcd for C2OH25CIN4: 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 7 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 7 Ex. R- Ar mp(°C) 1200a C-Me 2-ethylpiperidyl 2-Me-4-OMePh58- 59.5 1201b C-Me cyclobutylamino 2-Me-4-OMePh94.5- 96 1202c C-Me N(Me)CH 2 CH=CH 2 2-Me-4-OMePh oil 1203d C-Me N(CH 2 CH=CH 2 ) 2 2-Me-4-OMePh oil •133- 1204 C-Me N (Et ) CH 2 c- Pr 2 -Me -4 -OMePh 1205 β c-Me NHCH 2 - 2 - tetrahydrofuryl 2 -Me-4 -OMePh amorphous 1206ay C-Me N ( Pr) CH 2 c - Pr 2 -Me-4 -OMePh oil 1207az C-Me N(Me)Pr 2-Me-4-OMePh oil 1208f C-Me N(Me)Et 2-Me-4-OMePh oil 1209g C-Me N(Me)Bu 2-Me-4-OMePh oil 1210h C-Me N (Me) propargyl 2-Me-4-OMePh oil 12111 C-Me NH(CH(CH 3 )CH(CH 3 )CH 3 ) 2-Me-4-OMePh oil 1212 C-Me N (CH 2 CH 2 OMe) CH 2 CH=CH 2 2-Me-4-OMePh oil 1213k C-Me N(CH 2 CH 2 OMe)Me 2-Me-4-OMePh oil 1214 C-Me N(CH 2 CH 2 OMe)Et 2-Me-4-OMePh 1215 C-Me N(CH 2 CH 2 OMe)Pr 2-Me-4-OMePh 1216 C-Me N (CH 2 CH 2 OMe) CH 2 c-Pr 2-Me-4-OMePh 1217* C-Me NH(CH(CH 3 )CH 2 CH 3 ) 2-Me-4-OMePh oi] 1218 C-Me NHCH(c-Pr) 2 2-Me-4-OMePh 1219* C-Me NH-2-hexyl 2-Me-4-OMePh oil 122QO C-Me NH- 2 -propyl 2-Me-4-OMePh oil 122IP C-Me NHCH -2-tetrahydrofuryl 2-Me-4-OMePh amorphous 12229 C-Me NEt (cyclohexyl) 2-Me-4-OMePh oil 1223 C-Me 2-ethylpiperidyl 2,5-Me 2 -4-OMePh 1224 C-Me cyclobutylamino 2,5-Me 2 -4-OMePh 1225 C-Me N(Me)CH 2 CH=CH 2 2,5-Me 2 -4-OMePh 1226 . C-Me N(Et)CH 2 c-Pr 2,5-Me 2 -4-OMePh 1227 C-Me N(Pr)CH 2 c-Pr 2,5-Me 2 -4-OMePh 1228 C-Me N(Me)Pr 2,5-Me 2 -4-OMePh 1229 C-Me N(Me)Et 2,5-Me 2 -4-OMePh -134 - 1230 C--Me N(Me)Bu 2,5-Me 2 -4-OMePh 1231 C- -Me N (Me) propargyl 2,5-Me 2 -4-OMePh 1232 C- -Me NH(CH(CH 3 )CH(CH 3 )CH 3 ) 2,5-Me 2 -4-OMePh 1233 C- -Me N (CH 2 CH 2 OMe) CH 2 CH=-CH 2 2,5-Me 2 -4-OMePh 1234 C- -Me N(CH 2 CH 2 OMe)Me 2,5-Me -4-OMePh 1235 C- -Me N(CH 2 CH 2 OMe)Et 2,5-Me 2 -4-OMePh 1236 C- -Me N(CH 2 CH 2 OMe)Pr 2,5-Me 2 -4-OMePh 1237 C- -Me N (CH 2 CH 2 OMe) CH 2 c-Pr 2,5-Me 2 -4-OMePh 1238 C- -Me NH(CH(CH 3 )CH 2 CH 3 ) 2,5-Me 2 -4-OMePh 1239 C- -Me NHCH(c-Pr) 2 2,5-Me 2 -4-OMePh 1240 C- -Me 2 -ethylpiperidyl 4- OMe) 2 Ph 1241 C- -Me cyclobutylamino 4- OMe) 2 Ph 1245 C- -Me N(Me)CH 2 CH=CH 2 4- OMe) 2 Ph 1255 r C- -Me N(CH 2 CH=CH 2 ) 2 4- OMe) 2 Ph64.. 65.6 1256 c- -Me N(Et)CH 2 c-Pr 4- OMe) 2 Ph 1257 c- -Me N(Pr)CH 2 c-Pr 4- OMe) 2 Ph 1258 c- -Me N(Me)Pr 4- OMe) 2 Ph 1259 c- -Me N(Me)Et 4- OMe) 2 Ph 1260 c- -Me N(Me)Bu 4- OMe) 2 Ph 1261 c- -Me N (Me ) propargyl 4- OMe) 2 Ph 1262 c- -Me NH (CH (CH 3 ) CH (CH 3 ) CH 3 ) 4- OMe) 2 Ph 1263 c- -Me N(CH2CH 2 OMe)CH 2 CH=CH 2 4- OMe) 2 Ph 1264 c- -Me N(CH 2 CH 2 OMe)Me 4- OMe) 2 Ph 1265 c- -Me N(CH 2 CH 2 OMe)Et 4- OMe) 2 Ph 1266 C- -Me N(CH 2 CH 2 OMe) Pr 4- OMe) 2 Ph 1267 c- -Me N (CH 2 CH 2 OMe) CH 2 c-Pr 4- OMe) 2 Ph 1268 s c -Me NH(CH(CH 3 )CH 2 CH 3 ) 4- OMe) 2 Phl37 138.3 1269 c -Me NHCH(c-Pr) 2 2,4- (OMe) 2 Ph -135- 1270 fc C--Me N(CH 2 CH 2 OMe) 2 2,4-(OMe) 2 Ph oil 1271 u C- -Me NHCH(Et) 2 2,4- (OMe) 2 Phl28- 129.4 1272 C- -Me N(Et) 2 2, 4- (OMe) 2 Ph 1273 v C- -Me N(Pr) 2 2, 4- (OMe) 2 Ph 1274 C- -Me 2-ethylpiperidyl 2,4- OMe) 2 -5-MePh 1275 C- -Me cyclobutylamino 2,4- OMe) 2 -5-MePh 1276 C- -Me N(Me)CH 2 CH=CH 2 2,4- OMe) 2 -5-MePh 1277 C- -Me N(Et)CH 2 c-Pr 2,4- OMe) 2 -5-MePh 1278 c- -Me N(Pr)CH 2 c-Pr 2,4- OMe) 2 -5-MePh 1279 C- -Me N(Me) Pr 2,4- OMe) 2 -5-MePh 1280 C- -Me N(Me)Et 2,4- OMe) 2 -5-MePh 1281 C- -Me N(Me)Bu 2,4- OMe) 2 -5-MePh 1282 C- -Me N (Me) propargyl 2,4- OMe) 2 -5-MePh 1283 c- -Me NH(CH(CH 3 )CH(CH 3 )CH 3 ) 2 2,,44- ;OMe) 2 -5-MePh 1284 c- -Me (CH 2 CH 2 OMe) CH 2 CH=CH 2 2 2 ,, 44- OMe) 2 -5-MePh 1285 c- -Me N(CH 2 CH OMe)Me 2,4- 'OMe) -5-MePh 1286 c- -Me N(CH 2 CH 2 OMe)Et 2,4- v OMe) 2 -5-MePh 1287 C- -Me N(CH 2 CH 2 OMe) Pr 2,4- f OMe) 2 -5-MePh 1288 c- -Me N(CH 2 CH 2 OMe)CH 2 c-Pr 2 2,,44-- r OMe) 2 -5-MePh 1289 c- -Me NH(CH(CH 3 )CH 2 CH 3 ) 2,4- [OMe) 2 -5-MePh 1290 C- -Me NHCH(c-Pr) 2 2,4- (OMe) 2 -5-MePh 1291 c- -Me N(CH 2 CH 2 OMe) 2 2,4- (OMe) 2 -5-MePh 1292 c- -Me NHCH(Et) 2 2,4- (OMe) 2 -5-MePh 1293 c -Me N(Et) 2 2,4- (OMe) 2 -5-MePh 1294 c -Me 2 -ethylpiperidyl 2,4- (OMe) 2 -5-ClPh 1295 c -Me cyclobutylamino 2,4- (OMe) 2 -5-ClPh 1296 c -Me N(Me)CH 2 CH=CH 2 2,4- (OMe) 2 -5-ClPh 1297 c -Me N(Et)CH 2 c-Pr 2,4- (OMe) 2 -5-ClPh 1298 c -Me N(Pr)CH 2 c-Pr 2,4- (OMe) 2 -5-ClPh - 136 - 2,4- (OMe) 2 "5-ClPh 1299 C-Me N(Me)Pr 2,4- (OMe) 2 -5-ClPh 1300 C-Me N(Me)Et 1301 C-Me N(Me)Bu 2 ,4- (OMe) 2 -5-ClPh 1302 C-Me N (Me) propargyl 2,4- (OMe) 2 -5-ClPh 1303 C-Me NH(CH(CH 3 )CH(CH 3 )CH 3 ) 2,4- (OMe) 2 -5-ClPh 1304 C-Me N(CH 2 CH2θMe)CH2CH=CH 2 2,4- (OMe) 2 -5-ClPh 1305 C-Me N(CH 2 CH 2 OMe)Me 2 , 4- (OMe) 2 -5-ClPh 1306 C-Me N(CH 2 CH 2 OMe)Et 2 , 4- (OMe) 2 -5-ClPh 1307 C-Me N(CH 2 CH 2 OMe)Pr 2 , 4- (OMe) 2 -5-ClPh 1308 C-Me N(CH 2 CH 2 OMe)CH 2 c-Pr 2,4- (OMe) 2 -5-ClPh 1309 C-Me NH(CH(CH 3 )CH 2 CH 3 ) 2,4- (OMe) 2 -5-ClPh 1310 C-Me NHCH(c-Pr) 2 2,4- (OMe) 2 -5-ClPh 1311 C-Me N(CH 2 CH 2 OMe) 2 2,4- (OMe) 2 -5-ClPh 1312 C-Me NHCH(Et) 2 2,4- (OMe) -5-ClPh 1313 C-Me N(Et) 2 2,4- (OMe) 2 -5-ClPh 1314Y C-Me 2-ethylpiperidyl 2-Me-4,6- (OMe) 2 Ph 145-149 1315 z C-Me cyclobutylamino 2-Me-4,6- (OMe) 2 Ph 131-133 1316 aa C-Me N(Me)CH 2 CH=CH 2 2-Me-4,6- (OMe) Ph oil 1317 C-Me N(Et)CH 2 c-Pr 2-Me-4,6- (OMe) 2 Ph 1318 ab C-Me N ( Pr)CH 2 c-Pr 2-Me-4 , 6- (OMe) 2 Ph oil 1319 ac C-Me N(Me) Pr 2-Me-4,6- (OMe) 2 Ph oil 1320 ad C-Me N(Me)Et 2-Me-4,6- (OMe) 2 Ph oil 1321 ae C-Me N(Me) Bu 2-Me-4,6- (OMe) 2 Ph oil -137- 1322 C-Me N (Me) propargyl 2-Me-4,6- (OMe) 2 Ph 1323 C-Me NH(CH(CH 3 )CH(CH 3 )CH 3 ) 2-Me-4,6- ( OMe) 2 h 1324 C-Me N (CH 2 CH 2 OMe) CH 2 CH=CH; >2-Me-4,6- OMe) 2 h 1325 C-Me N(CH 2 CH 2 OMe)Me 2-Me-4,6- OMe) 2 Ph 1326 af C-Me N(CH 2 CH 2 OMe)Et 2-Me-4,6- OMe) 2 Ph oil 1327 C-Me N(CH 2 CH 2 OMe)Pr 2-Me-4,6- OMe) Ph 1328 a 9 C-Me N (CH 2 CH 2 OMe) CH 2 c-Pr 2-Me-4,6- OMe) 2 Ph oil 1329 ax C-Me NH(CH(CH 3 )CH 2 CH 3 ) 2-Me-4,6- OMe) 2 Ph 107-110 1330 C-Me NHCH(c-Pr) 2 2-Me-4,6- OMe) 2 P 1331 w C-Me N(CH 2 CH 2 OMe) 2 2-Me-4,6- OMe) 2 1332 C-Me NHCH(Et) 2 2-Me-4,6- OMe) Ph 1333 C-Me N(Et) 2 2-Me-4,6- OMe) 2 Ph 1334* C-Me NEt (Bu) 2-Me-4,6- OMe) 2 Ph oil 1335 C-Me 2 -ethylpiperidyl 2-Cl-4,6- OMe) 2 Ph 1336 C-Me cyclobutylamino ' 2-Cl-4,6- OMe) 2 Ph 1337 C-Me N(Me)CH 2 CH=CH 2 2-Cl-4,6- OMe) 2 Ph 1338 C-Me N(Et)CH 2 c-Pr 2-Cl-4,6- OMe) Ph 1339 C-Me N(Pr)CH 2 c-Pr 2-Cl-4,6- OMe) 2 Ph 1340 C-Me N(Me) Pr 2-Cl-4,6- OMe) 2 Ph 1341 C-Me N(Me)Et 2-Cl-4,6- OMe) 2 Ph 1342 C-Me N(Me)Bu 2-Cl-4,6- OMe) 2 Ph 1343 C-Me N (Me) propargyl 2-Cl-4,6- OMe) 2 Ph 1344 C-Me NH (CH (CH 3 ) CH (CH 3 ) CH 3 ) 2-Cl-4,6- OMe) 2 Ph 1345 C-Me N(CH 2 CH 2 OMe) CH 2 CH=CH 2 2-C1-4 , 6- (OMe) 2 Ph 1346 C-Me N(CH 2 CH 2 OMe)Me 2-Cl-4,6- (OMe 1 2 Ph 1347 C-Me N(CH 2 CH 2 OMe)Et 2-Cl-4,6- (OMe 2 Ph 1348 C-Me N(CH 2 CH 2 OMe) Pr 2-Cl-4,6- (OMe 2 P -138 - 1349 C-Me N (CH 2 CH 2 OMe) CH 2 c-Pr 2-C1-4 , 6- (OMe) 2 Ph 1350 C-Me NH(CH(CH 3 )CH 2 CH 3 ) 2 -Cl-4 , 6- (OMe) 2 Ph 1351 C-Me NHCH(c-Pr) 2 2-C1-4 , 6- (OMe) 2 Ph 1352 C-Me NHCH(Et) 2 2 -Cl-4 , 6- (OMe) 2 Ph 1353 C-Me N(Et) 2 2-C1-4 , 6- (OMe) 2 Ph 1354 C-Me 2-ethylpiperidyl 2-Cl-4-OMe-Ph 1355 C-Me cyclobutylamino 2-Cl-4-OMe-Ph 1356 C-Me N (Me) CH 2 CH=CH 2 2 -Cl -4-OMe-Ph 1357 C-Me N(Et)CH 2 c-Pr 2-Cl-4-OMe-Ph 1358 C-Me N(Pr)CH 2 c-Pr 2-Cl-4-OMe-Ph 1359 C-Me N(Me)Pr 2-Cl-4-OMe-Ph 1360 C-Me N(Me)Et 2 -Cl-4-OMe-Ph 1361 C-Me N(Me)Bu 2 -Cl-4-OMe-Ph 1362 C-Me N (Me) propargyl 2-Cl-4-OMe-Ph 1363 C-Me NH (CH (CH 3 ) CH (CH 3 ) CH 3 ) 2-Cl-4-OMe-Ph 1364 C-Me N (CH 2 CH 2 OMe) CH 2 CH=CH 2 2-Cl-4-OMe-Ph 1365 C-Me N (CH 2 CH 2 OMe) Me 2-Cl-4-OMe-Ph 1366 C-Me N (CH 2 CH 2 OMe) Et 2-Cl-4-OMe-Ph 1367 C-Me N(CH 2 CH 2 OMe)Pr 2-Cl-4-OMe-Ph 1368 C-Me N (CH 2 CH 2 OMe) CH 2 c-Pr 2-Cl-4-OMe-Ph 1369 C-Me NH(CH(CH 3 )CH 2 CH 3 ) 2-Cl-4-OMe-Ph 1370 C-Me NHCH(c-Pr) 2 2-Cl-4-OMe-Ph 1371 C-Me 2-ethylpiperidyl 2-Me-4 , 5- (OMe) Ph 1372 C-Me cyclobutylamino 2-Me-4 , 5- (OMe) Ph 1373 C-Me N (Me) CH 2 CH=CH 2 2-Me-4 , 5- (OMe) 2 Ph 1374 C-Me N(Et)CH 2 c-Pr 2-Me-4 , 5- (OMe) 2 Ph 1375 C-Me N(Pr)CH 2 c-Pr 2-Me-4 , 5- (OMe) 2 Ph 1376 C-Me N(Me)Pr 2-Me-4 , 5- (OMe) 2 Ph 1377 C-Me N(Me)Et 2 -Me-4 , 5- (OMe) 2 Ph 1378 C-Me N(Me)Bu 2-Me-4 , 5- (OMe) 2 Ph 1379 C-Me N (Me) propargyl 2-Me-4 , 5- (OMe) 2 Ph -139- 1380 C-Me NH(CH(CH 3 )CH(CH 3 )CH 3 ) 2-Me-4,5- OMe) Ph 1381 C-Me N(CH 2 CH 2 OMe) CH 2 CH--CH 2 2-Me-4 , 5- OMe) 2 Ph 1382 C-Me N(CH 2 CH 2 OMe)Me 2-Me-4,5- OMe) 2 Ph 1383 C-Me N(CH 2 CH 2 OMe)Et 2-Me-4,5- OMe) 2 Ph 1384 C-Me N(CH 2 CH 2 OMe)Pr 2-Me-4,5- OMe) 2 Ph 1385 C-Me N(CH 2 CH 2 OMe)CH 2 c-Pr 2-Me-4,5- OMe) 2 Ph 1386 C-Me NH(CH(CH 3 )CH 2 CH 3 ) 2-Me-4,5- OMe) 2 h 1387 C-Me NHCH(c-Pr) 2 2-Me-4,5- OMe) 2 Ph 1388 C-Me N(CH 2 CH 2 OMe) 2 2-Me-4,5- OMe) 2 Ph 1389 C-Me NHCH(Et) 2 2-Me-4,5- OMe) 2 Ph 1390 C-Me N(Et) 2 2-Me-4,5- OMe) 2 Ph 1391 C-Me NEt(Bu) 2-Me-4,5- OMe) 2 Ph 1392 C-Me 2-ethylpiperidyl 2-Cl-4,5- OMe) 2 Ph 1393 b C-Me cyclobutylamino 2-Cl-4,5- OMe) 2 Ph 121-122 1394 aι C-Me N(Me)CH 2 CH--CH 2 2-Cl-4,5- OMe) 2 Ph 122-126 1395 C-Me N(Et)CH 2 c-Pr 2-Cl-4,5- OMe) 2 Ph 1396 a -i C-Me N(Pr)CH 2 c-Pr 2-Cl-4,5- OMe) 2 Ph oil 1397 ak C-Me N(Me) Pr 2-Cl-4,5- OMe) 2 Ph 115-117 1398 al C-Me N(Me) Et 2-Cl-4,5- OMe) 2 Ph 115-119 1399™ C-Me N(Me)Bu 2-Cl-4,5- OMe) Ph oil 1400 C-Me N (Me) propargyl 2-Cl-4,5- 0Me) 2 Ph 1401 C-Me NH(CH(CH 3 )CH(CH 3 )CH 3 ) 2-Cl-4,5- OMe) 2 Ph 1402 C-Me N (CH 2 CH 2 OMe) CH 2 CH=CH 2 2-Cl-4, 5- OMe) 2 h 1403 C-Me N(CH 2 CH 2 OMe)Me 2-Cl-4,5- OMe) 2 Ph -140- 1404 an C-Me N(CH 2 CH 2 OMe)Et 2-C1-4 , 5- (OMe) 2 Ph oil 1405 C-Me N(CH 2 CH 2 OMe)Pr 2-C1-4 , 5- (OMe) 2 Ph 1406 o C-Me N(CH 2 CH 2 OMe)CH 2 c-Pr 2-C1-4 , 5- (OMe) Ph oil 1407 C-Me NH(CH(CH 3 )CH 2 CH 3 ) 2-Cl-4,5- (OMe) 2 P 1408 C-Me NHCH(c-Pr) 2 2-C1-4 , 5- (OMe) 2 Ph 1409 a P C-Me N(CH 2 CH 2 OMe) 2 2-C1-4 , 5- (OMe) 2 Ph oil 1410 ac ϊ C-Me NHCH(Et) 2 2-C1 -4,5- (OMe) 2 Ph 104-106 1411 ar C-Me N(Et) 2 2-C1 -4,5- (OMe) 2 Ph oil 1412 as C-Me NEt (Bu) 2-C1 -4,5- (OMe) 2 Ph oil 1413 C-Me 2 -ethylpiperidyl 2-C1 -4-OMe-5-MePh 1414 C-Me cyclobutylamino 2-C1 -4-OMe-5-MePh 1415 C-Me N(Me)CH 2 CH=CH 2 2-C1 -4-OMe-5-MePh 1416 C-Me N(Et)CH 2 c-Pr 2-C1 -4-OMe-5-MePh 1417 C-Me N(Pr)CH 2 c-Pr 2-C1 -4-OMe-5-MePh 1418 C-Me N(Me) Pr 2-C1 -4-OMe-5-MePh 1419 C-Me N(Me)Et 2-C1 -4-OMe-5-MePh 1420 C-Me N(Me)Bu 2-C1 -4-OMe-5-MePh 1421 C-Me N (Me) propargyl 2-C1 -4-OMe-5-MePh 1422 C-Me NH(CH(CH 3 )CH(CH 3 )CH 3 : I2-C1 -4-OMe-5-MePh 1423 C-Me N(CH 2 CH 2 OMe)CH 2 CH=CH 2 2-Cl -4-OMe-5-MePh 1424 C-Me N(CH 2 CH 2 OMe)Me 2-C1 -4-OMe-5-MePh 1425 C-Me N(CH 2 CH 2 OMe)Et 2-C1 -4-OMe-5-MePh 1426 C-Me N(CH 2 CH 2 OMe)Pr 2-C1 -4-OMe-5-MePh 1427 C-Me N(CH 2 CH 2 OMe)CH 2 c-Pr 2-C1 -4-OMe-5-MePh 1428 C-Me NH(CH(CH 3 )CH 2 CH 3 ) 2-C1 -4-OMe-5-MePh 1429 C-Me NHCH(c-Pr ) 2 2-C1 -4-OMe-5-MePh 1430 C-Me NHCH(Et) 2 2-C1 -4-OMe-5-MePh -141- 1431 C-Me N(Et) 2 2-Cl-4-OMe-5-MePh 1432 C-Me NEt (Bu) 2-Cl-4-OMe-5-MePh 1433 C-Me 2 -ethylpiperidyl 2-Cl-6-OMe-4-MePh 1434 C-Me cyclobutylamino 2-Cl-6-OMe-4-MePh 1435 C-Me N(Me)CH 2 CH=CH 2 2-Cl-6-OMe-4-MePh 1436 C-Me N(Et)CH 2 c-Pr 2-Cl-6-OMe-4-MePh 1437 C-Me N(Pr)CH 2 c-Pr 2 -cl-6-OMe-4-MePh 1438 C-Me N(Me) Pr 2-Cl-6-OMe-4-MePh 1439 C-Me N(Me)Et 2-Cl-6-OMe-4-MePh 1440 C-Me N(Me)Bu 2-Cl-6-OMe-4-MePh 1441 C-Me N (Me) propargyl 2-Cl-6-OMe-4-MePh 1442 C-Me NH(CH(CH 3 )CH(CH 3 )CH 3 )2-Cl-6-OMe-4-MePh 1443 C-Me N(CH 2 CH 2 OMe)CH 2 CH=CH 2 2-Cl-6-OMe-4-MePh 1444 C-Me N(CH 2 CH 2 OMe)Me 2-Cl-6-OMe-4-MePh 1445 C-Me N(CH 2 CH 2 OMe)Et 2-Cl-6-OMe-4-MePh 1446 C-Me N(CH 2 CH 2 OMe) Pr 2-Cl-6-OMe-4-MePh 1447 C-Me N(CH 2 CH 2 OMe)CH 2 c-Pr 2-Cl-6-OMe-4-MePh 1448 C-Me NH(CH(CH 3 )CH 2 CH 3 ) 2-Cl-6-OMe-4-MePh 1449 C-Me NHCH(c-Pr) 2 2-Cl-6-OMe-4-MePh 1450 C-Me NHCH(Et) 2 2-Cl-6-OMe-4-MePh 1451 C-Me N(Et) 2 2-Cl-6-OMe-4-MePh 1452 C-Me NEt (Bu) 2-Cl-6-OMe-4-MePh 1453 C-Me 2 -ethylpiperidyl 2,6-Me 2 -4-OMePh 1454 C-Me cyclobutylamino 2,6-Me 2 -4-OMePh 1455 C-Me N(Me)CH 2 CH=CH 2,6-Me 2 -4-OMePh 1456 C-Me N(Et) CH 2 c-Pr 2, 6-Me -4-OMePh 1457 C-Me N(Pr)CH 2 c-Pr 2,6-Me 2 -4-OMePh 1458 C-Me N(Me) Pr 2,6-Me -4-OMePh 1459 C-Me N(Me) Et 2,6-Me 2 -4-OMePh 1460 C-Me N(Me) Bu 2,6-Me 2 -4-OMePh 1461 C-Me N (Me) propargyl 2,6-Me -4-OMePh - 142 - 1462 C--Me NH(CH(CH 3 )CH(CH 3 )CH 3 ) 2,6-Me 2 -4-OMePh 1463 C- -Me N (CH 2 CH 2 OMe) CH 2 CH=CH 2 2,6-Me 2 -4-OMePh 1464 C -Me N(CH 2 CH 2 OMe)Me 2,6-Me 2 -4-OMePh 1465 C- -Me N(CH 2 CH 2 OMe)Et 2,6-Me 2 -4-OMePh 1466 c -Me N(CH 2 CH 2 OMe)Pr 2,6-Me 2 -4-OMePh 1467 c- -Me N (CH 2 CH 2 OMe) CH 2 c-Pr 2,6-Me 2 -4-OMePh 1468 c- -Me NH(CH(CH 3 )CH 2 CH 3 ) 2,6-Me 2 -4-OMePh 1469 c- -Me NHCH(c-Pr) 2 2,6-Me 2 -4-OMePh 1470 c- -Me NHCH(Et) 2 2,6-Me 2 -4-OMePh 1471 c- -Me N(Et) 2 2,6-Me 2 -4-OMePh 1472 c- -Me NEt (Bu) 2,6-Me 2 -4-OMePh 1473 c- -Me 2-ethylpiperidyl 2-Cl-4-OMe-5-FPh 1474 c- -Me cyclobutylamino 2-Cl-4-OMe-5-FPh 1475 be c- -Me N(Me)CH 2 CH=CH 2 2-Cl-4-OMe-5-FPh oil 1476 c- -Me N(Et)CH 2 c-Pr 2-Cl-4-OMe-5-FPh 1478 c- -Me N(Pr)CH 2 c-Pr 2-Cl-4-OMe-5-FPh 1479 bb c- -Me N(Me) Pr 2-Cl-4-OMe-5-FPh oil 1480 bc C- -Me N(Me)Et 2-Cl-4-OMe-5-FPh oil 1481 c- -Me N(Me)Bu 2-Cl-4-OMe-5-FPh 1482 c- -Me N (Me) propargyl 2 -Cl-4-OMe-5-FPh 1483 c- -Me NH(CH(CH 3 )CH(CH 3 )CH 3 ) 2 -Cl-4 -OMe-5-FPh 1484 c- -Me N(CH 2 CH 2 OMe)CH2CH=CH 2 2-Cl-4-OMe-5-FPh 1485 c- -Me N(CH 2 CH 2 OMe)Me 2-Cl-4-OMe-5-FPh 1486 c- -Me N(CH 2 CH 2 OMe)Et 2 -Cl-4-OMe-5-FPh 1487 c- -Me N(CH 2 CH 2 OMe) Pr 2-Cl-4-OMe-5-FPh 1488 C- -Me N(CH 2 CH 2 OMe)CH 2 c-Pr 2-Cl-4-OMe-5-FPh 1489 bd c- -Me NH(CH(CH 3 )CH 2 CH 3 ) 2 -Cl-4 -OMe-5-FPh solid -143- 1490 C--Me NHCH(c-Pr) 2 2-Cl-4-OMe-5-FPh 1491 be C- -Me NHCH(Et ) 2-Cl-4-OMe-5-FPh oil 1492 bf C- -Me N(Et) 2 2-Cl-4-OMe-5-FPh 96-9. 1493 bg C- -Me NEt (Bu) -Cl-4 -OMe -5-FPh oil 1494 C- -Me 2 -ethylpiperidyl 2-•Cl-4-OMe- •6-MePh 1495 C- -Me cyclobutylamino 2-■Cl-4-OMe- •6-MePh 1496 C- -Me N(Me)CH 2 CH=CH 2 2--Cl-4-OMe- •6-MePh 1497 C- -Me N(Et)CH 2 c-Pr 2- -Cl-4-OMe- 6-MePh 1498 C- -Me N(Pr)CH 2 c-Pr 2- •Cl-4-OMe- 6-MePh 1499 C- -Me N(Me)Pr 2- •Cl-4-OMe- 6-MePh 1500 C- -Me N(Me)Et 2-•Cl-4-OMe-6-MePh 1501 C- -Me N(Me)Bu 2-•Cl-4-OMe-6-MePh 1502 c- -Me N (Me) propargyl 2-•Cl-4-OMe- 6-MePh 1503 c- -Me NH(CH(CH 3 )CH(CH 3 )CH 3 )2-•Cl-4-OMe-6-MePh 1504 c- -Me N(CH 2 CH 2 OMe)CH 2 CH=CH 2 2- •Cl-4-OMe- 6-MePh 1505 c- -Me N(CH 2 CH 2 OMe)Me 2- ■ Cl-4-OMe- 6-MePh 1506 c- -Me N(CH 2 CH 2 OMe)Et 2- Cl-4-OMe- 6-MePh 1507 c- -Me N(CH 2 CH 2 OMe)Pr 2- Cl-4-OMe- 6-MePh 1508 c- -Me N(CH 2 CH 2 OMe)CH 2 c-Pr 2- Cl-4-OMe- 6-MePh 1509 c- -Me NH(CH(CH 3 )CH 2 CH 3 ) 2- Cl-4-OMe- 6-MePh 1510 c- -Me NHCH(c-Pr) 2 2- Cl-4-OMe- 6-MePh 1511 c- -Me NHCH(Et) 2 2- Cl-4-OMe- 6-MePh 1512 c- -Me N(Et) 2 2- Cl-4-OMe- 6-MePh 1513 c- -Me NEt(Bu) 2- Cl-4-OMe- • 6-MePh 1514 c- -Me 2 -ethylpiperidyl 6-Me 2 N-4 -Me- pyrid-3 -yl 1515 C-Me cyclobutylamino 6-Me 2 N-4-Me- pyrid-3 -yl 1516 C-Me N(Me)CH 2 CH=CH 2 6-Me 2 N-4 -Me- pyrid-3 -yl -144- 1517 C-Me N(Et)CH 2 c-Pr 6-Me 2 N-4-Me- pyrid-3-yl 1518 C-Me N(Pr)CH 2 c-Pr 6-Me 2 N-4-Me- pyrid-3-yl 1519 C-Me N(Me)Pr 6-Me 2 N-4-Me- pyrid-3-yl 1520 C-Me N(Me)Et 6-Me 2 N-4-Me- pyrid-3-yl 1521 C-Me N(Me)Bu 6-Me 2 N-4-Me- pyrid-3-yl 1522 C-Me N (Me) propargyl 6-Me 2 N-4-Me- pyrid-3-yl 1523 C-Me NH (CH (CH 3 ) CH (CH 3 ) CH 3 ) 6-Me 2 N-4-Me- pyrid-3-yl 1524 C-Me N (CH 2 CH 2 OMe) CH CH=CH 2 6-Me 2 N-4-Me- pyrid-3-yl 1525 C-Me N(CH 2 CH 2 OMe)Me 6-Me 2 N-4-Me- pyrid-3-yl 1526 at C-Me N(CH 2 CH 2 OMe)Et 6-Me 2 N-4-Me- oil pyrid-3 -yl 1527 C-Me N(CH 2 CH 2 OMe)Pr 6-Me 2 N-4-Me- pyrid-3-yl 1528 C-Me N (CH 2 CH 2 OMe) CH 2 c-Pr 6-Me 2 N-4-Me- pyrid-3-yl 1529 C-Me NH(CH(CH 3 )CH 2 CH 3 ) 6-Me 2 N-4-Me- pyrid-3-yl 1530 C-Me NHCH(c-Pr) 2 6-Me 2 N-4-Me- pyrid-3-yl 1531 au C-Me N(CH 2 CH 2 OMe) 2 6-Me 2 N-4-Me- pyrid-3-yl 103-104 1532 av C-Me NHCH(Et) 2 6-Me 2 N-4-Me- -145- pyrid-3 -yl 153-154 1533 aw C-Me N(Et) 2 6-Me 2 N-4-Me- pyrid-3-yl 117-118 1534 C-Me 2 -ethylpiperidyl 6-MeO-4-Me- pyrid-3-yl 1535 C-Me cyclobutylamino 6-MeO-4-Me- pyrid-3-yl 1536 C-Me N(Me)CH 2 CH=CH 2 6-MeO-4-Me- pyrid-3-yl 1537 C-Me N(Et)CH 2 c-Pr 6-Me04-Me- pyrid-3-yl 1538 C-Me N(Pr)CHc-Pr 6-MeO-4-Me- pyrid-3-yl 1539 C-Me N(Me)Pr 6-MeO-4-Me- pyrid-3-yl 1540 C-Me N(Me)Et 6-MeO-4-Me- pyrid-3-yl 1541 C-Me N(Me)Bu 6-MeO-4-Me- pyrid-3-yl 1542 C-Me (Me) propargyl 6-MeO-4-Me- pyrid-3-yl 1543 C-Me NH (CH (CH 3 ) CH (CH 3 ) CH 3 ; 6-MeO-4-Me- pyrid-3-yl 1544 C-Me (CH 2 CH 2 OMe) CH 2 CH=CH 2 6-MeO-4-Me- pyrid-3-yl 1545 C-Me N(CH 2 CH 2 OMe)Me 6-MeO-4-Me- pyrid-3-yl 1546 C-Me N(CH 2 CH 2 OMe)Et 6-MeO-4-Me- pyrid-3-yl 1547 C-Me N(CH 2 CH 2 OMe) Pr 6-MeO-4-Me- pyrid-3-yl •146- 1548 C-Me N (CH 2 CH 2 OMe) CH 2 c-Pr 6-MeO-4-Me- pyrid-3-yl 1549 C-Me NH(CH(CH 3 )CH 2 CH 3 : 6-MeO-4-Me- pyrid-3-yl 1550 C-Me NHCH(c-Pr) 2 6-MeO-4-Me- pyrid-3-yl 1551 C-Me N(CH 2 CH 2 OMe) 2 6-MeO-4-Me- pyrid-3-yl 1552 C-Me NHCH(Et) 2 6-MeO-4-Me- pyrid-3-yl 1553 C-Me N(Et) 2 6-MeO-4-Me- pyrid-3-yl 1554 C-Me 2 -ethylpiperidyl 4,6-Me 2 - pyrid-3-yl 1555 C-Me cyclobutylamino 4,6-Me 2 - pyrid-3-yl 1556 C-Me N(Me)CH 2 CH=CH 2 4,6-Me 2 - pyrid-3-yl 1557 C-Me N(Et)CH 2 c-Pr 4,6-Me 2 - pyrid-3-yl 1558 C-Me N(Pr)CH 2 c-Pr 4,6-Me 2 - pyrid-3-yl 1559 C-Me N(Me) Pr 4,6-Me 2 - pyrid-3-yl 1560 C-Me N(Me)Et 4,6-Me 2 - pyrid-3-yl 1561 C-Me N(Me)Bu 4,6-Me 2 - pyrid-3-yl 1562 C-Me N (Me) propargyl 4,6-Me 2 - pyrid-3-yl 1563 C-Me NH(CH(CH 3 )CH(CH 3 )CH 3 ) 4,6-Me 2 - pyrid-3-yl ■147- 1564 C-Me N (CH 2 CH 2 OMe) CH 2 CH=CH 2 4,6-Me 2 - pyrid-3-yl 1565 C-Me N(CH 2 CH 2 OMe)Me 4,6-Me 2 - pyrid-3-yl 1566 C-Me N (CH 2 CH 2 OMe) Et 4,6-Me 2 - pyrid-3-yl 1567 C-Me N (CH 2 CH 2 OMe) Pr 4,6-Me 2 - pyrid-3-yl 1568 C-Me N (CH 2 CH 2 OMe) CH 2 c-Pr 4,6-Me 2 - pyrid-3-yl 1569 C-Me NH (CH (CH 3 ) CH 2 CH 3 ) 4,6-Me 2 - pyrid-3-yl 1570 C-Me NHCH(c-Pr) 2 4,6-Me 2 - pyrid-3-yl 1571 C-Me N (CH 2 CH 2 OMe) 4,6-Me 2 - pyrid-3-yl 1572 C-Me NHCH(Et) 2 4,6-Me 2 - pyrid-3-yl 1573 C-Me N(Et) 2 4,6-Me 2 - pyrid-3 -yl 1574 C-Me 2 -ethylpiperidyl 2,6-Me 2 - pyrid-3-yl 1575 C-Me cyclobutylamino 2,6-Me 2 ~ pyrid-3-yl 1576 C-Me N (Me) CH 2 CH=CH 2 2,6-Me 2 - pyrid-3-yl 1577 C-Me N(Et)CH 2 c-Pr 2,6-Me 2 - pyrid-3-yl 1578 C-Me N(Pr)CH 2 c-Pr 2,6-Me 2 - pyrid-3 -yl 1579 C-Me N(Me)Pr 2,6-Me 2 - pyrid-3-yl ■ 148- 1580 C-Me N(Me)Et 2,6-Me 2 - pyrid-3-yl 1581 C-Me N(Me)Bu 2,6-Me 2 - pyrid-3-yl 1582 C-Me N (Me) propargyl 2,6-Me 2 - pyrid-3-yl 1583 C-Me NH (CH (CH 3 ) CH (CH 3 ) CH 3 ) 2,6-Me 2 - pyrid-3-yl 1584 C-Me N (CH 2 CH 2 OMe) CH 2 CH=CH 2 2,6-Me 2 - pyrid-3 -yl 1585 C-Me N(CH 2 CH 2 OMe)Me 2,6-Me 2 - pyrid-3-yl 1586 C-Me N (CH 2 CH 2 OMe) Et 2,6-Me 2 - pyrid-3-yl 1587 C-Me N (CH 2 CH 2 OMe) Pr 2,6-Me 2 - pyrid-3-yl 1588 C-Me (CH 2 CH 2 OMe) CH 2 c-Pr 2,6-Me 2 - pyrid-3-yl 1589 C-Me NH (CH (CH 3 ) CH 2 CH 3 ) 2,6-Me 2 - pyrid-3 -yl 1590 C-Me NHCH(c-Pr) 2 2,6-Me 2 - pyrid-3-yl 1591 C-Me N (CH 2 CH 2 OMe) 2 2,6-Me 2 - pyrid-3-yl 1592 C-Me NHCH(Et) 2 2,6-Me 2 - pyrid-3-yl 1593 C-Me N(Et) 2 2,6-Me 2 - pyrid-3-yl 1594 C-Me 2 -ethylpiperidyl 4-MeO-6-Me- pyrid-3 -yl 1595 C-Me cyclobutylamino 4-MeO-6-Me- pyrid-3-yl 1596 C-Me N (Me) CH 2 CH--CH 2 4-MeO-6-Me- -149- pyrid-3-yl 1597 C-Me N(Et)CH 2 c-Pr 4-MeO-6-Me- pyrid-3-yl 1598 C-Me N(Pr)CH 2 c-Pr 4-MeO-6-Me- pyrid-3-yl 1599 C-Me N(Me)Pr 4-MeO-6-Me- pyrid-3-yl 1600 C-Me N(Me)Et 4-MeO-6-Me- pyrid-3-yl 1601 C-Me N(Me)Bu 4-MeO-6-Me- pyrid-3-yl 1602 C-Me N (Me) propargyl 4-MeO-6-Me- pyrid-3-yl 1603 C-Me NH (CH (CH 3 ) CH (CH 3 ) CH 3 ) 4-MeO-6-Me- pyrid-3-yl 1604 C-Me N (CH 2 CH 2 OMe) CH 2 CH=CH 2 4-MeO-6-Me- pyrid-3-yl 1605 C-Me N(CH 2 CH 2 OMe)Me 4-MeO-6-Me- pyrid-3-yl 1606 C-Me N (CH 2 CH 2 OMe) Et 4-MeO-6-Me- pyrid-3-yl 1607 C-Me N (CH 2 CH 2 OMe) Pr 4-MeO-6-Me- pyrid-3-yl 1608 C-Me N (CH 2 CH 2 OMe) CH 2 c-Pr 4-MeO-6-Me- pyrid-3-yl 1609 C-Me NH(CH(CH 3 )CH 2 CH 3 ) 4-MeO-6-Me- pyrid-3-yl 1610 C-Me NHCH(c-Pr) 2 4-MeO-6-Me- pyrid-3-yl 1611 C-Me N (CH 2 CH 2 OMe) 2 4-MeO-6-Me- pyrid-3-yl 1612 C-Me NHCH(Et) 2 4-MeO-6-Me- pyrid-3-yl •150- 1613 C-Me N(Et) 2 4-MeO-6-Me- pyrid- 3-yl 1614 C-Me 2 -ethylpiperidyl 2-Br-4,5- OMe) 2 Ph 1615 C-Me cyclobutylamino 2-Br-4,5- OMe 2 Ph 1616 C-Me N(Me)CH 2 CH=CH 2 2-Br-4,5- OMe 2 Ph 1617 C-Me N(Et)CH 2 c-Pr 2-Br-4,5- OMe 2 Ph 1618 C-Me N(Pr)CH 2 c-Pr 2-Br-4,5- OMe Ph 1619 C-Me N(Me)Pr 2-Br-4,5- OMe 2 Ph 1620 C-Me N(Me)Et 2-Br-4,5- OMe Ph 1621 C-Me N(Me)Bu 2-Br-4,5- OMe 2 Ph 1622 C-Me N (Me) propargyl 2-Br-4,5- OMe 2 Ph 1623 C-Me NH(CH(CH 3 )CH(CH 3 )CH 3 ) 2-Br-4,5- OMe 2 Ph 1624 C-Me N (CH 2 CH 2 OMe) CH 2 CH=CH 2 2-Br-4 , 5- OMe 2 Ph 1625 C-Me N(CH 2 CH 2 OMe)Me 2-Br-4,5- OMe 2 Ph 1626 C-Me N(CH 2 CH 2 OMe)Et 2-Br-4,5- OMe 2 Ph 1627 C-Me N(CH 2 CH 2 OMe)Pr 2-Br-4,5- OMe 2 Ph 1628 C-Me N (CH 2 CH 2 OMe) CH 2 C-Pr 2-Br-4,5- OMe 2 Ph 1629 C-Me NH(CH(CH 3 )CH 2 CH 3 ) 2-Br-4,5- OMe) Ph 1630 C-Me NHCH(c-Pr) 2 2-Br-4,5- OMe) 2 Ph 1631 C-Me N(CH 2 CH 2 OMe) 2 2-Br-4,5- OMe) 2 Ph 1632 C-Me NHCH(Et) 2 2-Br-4, 5- OMe 2 Ph 1633 C-Me N(Et) 2 2-Br-4,5- OMe 2 Ph 1634 C-Me NEt (Bu) 2-Br -4,5- (OMe) 2 Ph Notes for Table 7 : a) CI-MS: 330 (M + H) + b) CI-MS: 338 (M + H) + C) CI-MS: 338 (M + H) + d) CI-MS: 400 (M + H) + f) CI-MS: 326 (M + H) + g) CI-MS: 354 (M + H) + -151- h) CI -MS 336 (M + H) + CI -MS 354 (M + H) + j ) CI -MS 378 (M + H) + k) CI-HRMS: Calcd 356.2087 (M + H) + , Found: 356.2071: m) CI-MS: 340 (M + H) + ; n) CI-MS: 368 (M + H) + , o) CI-MS: 326 (M + H) + , P) CI-MS: 368 (M + H) + ; q) CI-MS: 394 (M + H) + ; r) CI-HRMS: Calcd 380.2087 (M + H) + Found 380 .2078 s ) CI-HRMS: Calcd 356.2008 (M + H) + Found 356.1997 t ) CI-HRMS: Calcd 416.2220 (M + H) + Found 416.2005 u) CI-HRMS: Calcd 370.2243 (M + H) + Found 370.2246 v) CI-HRMS: Calcd 380.2400 (M + H) + Found 384.2382 w) CI-HRMS: Calcd 429.2376 (M + H) + Found 429.2358 X ) CI-HRMS: Calcd 397.2478 (M + H) + Found 397.2484 y ) CI-HRMS: Calcd 410.5438 (M + H) + Found 410.2558 z ) CI-HRMS: Calcd 368.4625 (M + H) + Found 368.2100 aa) CI-HRMS: Calcd 368.2090 (M + H) + Found 368.4625 ab) CI-MS 410 (M + H) + ; ac ) CI-HRMS: Calcd 370.4785 (M + H) + Found : 370.2246; ad) CI-HRMS: Calcd 356.4514 (M + H) + Found : 356.2086; ae ) CI-MS 384 (M + H) + ; af ) CI-MS 400 (M + H) + ; ag) CI-MS 426 (M + H) + ; ah) CI-HRMS: Calcd 388.1553 (M + H) + Found : 388 1554 ai ) CI-HRMS: Calcd 388.1540 (M + H) + Found : 358 1546 aj ) CI-HRMS: Calcd 430.2005 (M + H) + Found : 430 2006 ak) CI-HRMS: Calcd 390.1683 (M + H) + Found : 390 1682 al ) CI-HRMS: Calcd 376.1554 (M + H) + Found : 376 1548 am) CI-HRMS: Calcd 404.1853 (M + H) + Found : 404 1850 an) CI-HRMS: Calcd 420.1810 (M + H) + Found : 420 1809 - 152 ao) Cl -HRMS: Calcd 446 1946 (M + H) + Found : 446 1949 ap) Cl -HRMS: Calcd 450 1917 (M + H) + Found : 450 1913 aq) Cl -HRMS : Calcd 404 1839 (M + H) + , Found : 404 1846 ar) Cl -HRMS: Calcd 390 1678 (M + H) + , Found : 390 .1680 as) Cl -HRMS: Calcd 418 2010 (M + H) + , Found : 418 .2012 at) Cl -HRMS: Calcd 384 2512 (M + H) + , Found : 384 2506 au) Cl -HRMS: Calcd 414 2617 (M + H) + Found : 414 2600 av) Cl -HRMS: Calcd 367 2484 (M + H) + Found : 367 2477 aw) Cl -HRMS : Calcd 354 2406 (M + H) + Found : 354 2388 ax) Cl -MS 370 (M + H) + , ay) Cl -MS 380 (M + H) + ; az) Cl -MS 340 (M + H) + ; ba) Cl -HRMS: Calcd 376 1340 (M + H) + Found: 376 1347 bb) Cl -HRMS: Calcd 378 1497 (M + H) + Found : 378 1495 be) Cl -HRMS: Calcd 364 1340 (M + H) + Found : 364 1333 bd) Cl- -HRMS : Calcd 378 1593 (M + H) + Found : 378 1498 be) Cl- -HRMS: Calcd 392 1653 (M + H) + Found : 392 1649 bf) CI- -HRMS: Calcd 378 1497 (M + H) + Found : 378 1489 bg) CI- -HRMS: Calcd 406 1810 (M. + H) + Found : 406 1819 The examples delineated in TABLE 8 may be prepared by the methods outlined in Examples 1A, IB, 432', 433, 434, Commonly used abbreviations are: Ph is phenyl, Pr is propyl, Me is methyl, Et is ethyl, Bu is butyl, cPr is cyclopropyl, Ex is Example, EtOAc is ethyl acetate. TABLE 8 •153 Ex. R S 1 Ar -s___°___. 2 000 Me N(CH CH 2 OMe) 2 2 ,4-Cl 2 -P-- 2 001 Me N(Bu) Et 2 ,4-Cl 2 -Ph 2 002 Me NHCH(Et)CH 2 OMe 2 ,4-Cl -Ph 003 Me N(Pr)CH 2 CH 2 CN 2 ,4-Cl 2 -Ph 2 004 Me NH-3-pentyl 2 ,4-Cl 2 -Ph 2 005 Me NHCH(CH2θMe)2 2 ,4-Cl 2 -Ph 2 006 Me NHCH(Et) 2 2,4-Me -Ph 2 007 Me NHCH ( CH 2 OMe ) 2 ,4-Me 2 -Ph 2 008 Me N(CH2CH2θMe ) 2 2 ,4-Me -Ph 2 009 Me N(c-Pr)CH 2 CH 2 CN 2 ,4-Me 2 -Ph 2010 Me N(CH 2 CH OMe) 2 -Cl,4-MePh 2 011 Me NHCH (CH 2 OMe) 2 2 -Cl,4-MeP 2 012 Me NHCH(Et) 2 2-Cl,4-MePh 2 013 Me NEt 2 2 ,4-Me 2 -Ph 014 Me N(Pr)CH2CH 2 CN 2 ,4-Me 2 -Ph 2 015 Me N(Bu)CH 2 CH2CN 2 ,4-Me -Ph 2 016 Me NHCH(Et)CH 2 OMe 2,4-Me -P 2 017 Me NHCH ( Et ) 2 2 -Me,4-MeOPh 2 018 Me NHCH ( CH OMe ) 2 2 -Me,4-MeOPh 2 019 Me ( CH2CH2θMe ) 2 2 -Me,4-MeOPhll5 116 2 020 Me (S) -NHCH(CH 2 CH 2 OMe) - 2 -Me,4-MeOPh -154 - 2 0 1 ( CH 2 OMe ) 2 0 22 Me (S ) -NHCH (CH 2 CH 2 OMe) ,4-Me 2 -Ph 2 0 2 3 ( CH 2 OMe ) 2 0 2 4 Me N ( CH2CH 2 OMe ) 2 2 -Me,4-ClPh 20 2 5 Me NHEt ,4-Me 2 -Ph 20 2 6 Me NHCH (Et ) 2 2 -Me,4-ClPh 2 027 Me NHCH(CH 2 OMe ) 2 2 -Me,4-ClPh 2 0 2 8 Me N(Ac)Et ,4-Me 2 -Ph 2 0 2 9 Me (S) -NHCH(CH 2 CH 2 OMe) 2 -Me,4-ClPh 030 (CH2θMe) 2031 Me N(Pr)CH 2 CH2CN -Me,4-MeOPh 2 032 Me NEt2 -Me,4-MeOPh 2033 Me (S) -NHCH(CH 2 CH2θMe) 2-Cl,4-MePh 2 034 (CH2θMe) 2 035 Me NEt 2 2-Cl,4 -MePh 2 036 Me N(c-Pr)CH 2 CH 2 CN 2 -Me, 4- ■MeOPh 2 037 Me N(c-Pr)CH CH 2 CN 2-Cl,4 -MePh 2 038 Me NHCH(Et)CH2θMe 2 -Me, 4- -MeOPh 2 039 Me NHCH(Et)CH2θMe 2-Cl,4 -MePh 2 040 Me NHCH(CH 2 OMe) 2 2-C1-4- •MeOPh 2041 Me N ( CH 2 CH 2 OMe)2 2-C1-4- MeOPh 2 04 2 Me NHCH(Et)CH2θMe 2-C1-4- MeOPh 043 Me N(c-Pr)CH 2 CH 2 CN 2-C1-4- MeOPh 2 044 Me NEt 2 2-C1-4- MeOPh 2 045 Me NH-3-pentyl 2-C1-4- MeOPh 2046 Me NHCH (Et) CH 2 CH 2 OMe 2-C1-4- MeOPh 2 047 Me NHCH (Me) CH2CH 2 OMe 2-C1-4- MeOPh 2 048 Me NHCH(Et) CH 2 CH 2 OMe 2-Br-4- MeOPh 2 049 Me NHCH (Me) CH 2 CH 2 OMe 2 -Br-4- MeOPh 2 050 Me NHCH ( Et ) CH 2 CH2θMe 2 -Me-4- MeOPh 2051 Me NHCH (Me) CH 2 CH 2 OMe 2 -Me-4- MeOPh 2 05 2 Me NHCH(CH2θMe) 2 2-Cl-4,5- (MeO) 2 Ph -155- 2 053 Me N(CH 2 CH 2 OMe ) 2 2-C1-4, MeO) 2P 2 054 Me NHCH (Et)CH 2 OMe 2-C1-4 5- MeO) 2 h 2 055 Me N(c-Pr)CH CH CN 2-C1-4 5- MeO) 2?h 2 056 Me NEt2 2-C1-4 5- MeO) 2Ph 2057 Me NH-3-pentyl 2-C1-4 5- !MeO) 2Ph 2 058 Me NHCH (Et) CH 2 CH 2 OMe 2-C1-4 5- MeO))2?h 2 059 Me NHCH (Me) CH2CH2<->Me 2-C1-4 5- MeO)) 2 Ph 2 060 Me NHCH (CH 2 OMe) 2 2-Br-4 5- MeO) 2 Ph 2 061 Me N(CH 2 CH2θMe ) 2 2 -Br-4 5- MeO) 2 P 2 06 2 Me NHCH (Et)CH 2 OMe 2 -Br-4 5- MeO) 2 Ph 2 063 Me N(c-Pr)CH2CH 2 CN 2 -Br-4 5- ;MeO)2Ph 2 064 Me NEt 2 -Br-4 5- MeO) 2P 2 065 Me NH-3-pentyl 2-Br-4 5- MeO) 2 Ph 2 066 Me NHCH (Et) CH CH2θMe 2-Br-4 5- MeO) Ph 2 067 Me NHCH (Me) CH2CH 2 OMe 2 -Br-4 5- MeO) Ph 2 068 Me NHCH (CH 2 OMe) 2 2-C1-4 6- MeO) 2 Ph 2 069 Me N(CH 2 CH 2 OMe ) 2 2-C1-4 6- MeO) 2 Ph 2 070 Me NHCH (Et)CH 2 OMe 2-C1-4 6- !MeO) 2 Ph 2 071 Me N(c-Pr)CH 2 CH 2 CN 2-C1-4 6- MeO) 2Ph 2 07 2 Me NEt 2 2-C1-4 6- MeO) 2Ph 2073 Me NH-3-pentyl 2-C1-4 6- MeO) 2 Ph 2074 Me NHCH (Et) CH 2 CH2θMe 2-C1-4 6- MeO) 2 Ph 2075 Me NHCH (Me) CH2CH 2 OMe 2-C1-4 6- MeO) 2 Ph 2076 Me NHCH ( CH 2 OMe ) 2 2-Me-4 6- MeO)2Ph 2 077 Me N(CH 2 CH2θMe) 2 2-Me-4 6- MeO)2Ph 2 078 Me NHCH(Et)CH 2 OMe 2-Me-4 6- !MeO) 2Ph 2 079 Me N(c-Pr)CH 2 CH 2 CN 2-Me-4 6- MeO)2 h 2080 Me NEt 2 2-Me-4 6- MeO) 2 Ph 2081 Me NH-3-pentyl 2-Me-4 6- MeO) Ph 2082 Me NHCH (Et) CH 2 CH2θMe 2-Me-4 6- MeO) 2 Ph 2083 Me NHCH(Me)CH2CH 2 OMe 2-Me-4 6- MeO) 2P 2084 Me N(c-Pr)CH 2 CH 2 CN 2-Br-4 6- MeO) 2P -156- 2 085 Me NEt 2 2-Br-4,6- (MeO) 2 Ph 2 086 Me NH-3-pentyl 2-Br-4,6- (MeO) 2 Ph 2 087 Me NHCH (Et) CH 2 CH 2 OMe 2-Br-4,6- (MeO) 2 Ph 2 088 Me NHCH (Me) CH 2 CH 2 OMe 2-Br-4,6- (MeO) Ph 2 089 Me NHCH(Et)CH 2 CH 2 OMe 2 -Me-4 -MeOPh 2 090 Me NHCH (Me) CH 2 CH 2 OMe 2-Me-4 -MeOPh 2091 Me NHCH(CH2θMe ) 2 2 -MeO -4 -MePh 2092 Me N(CH 2 CH 2 OMe) 2 2 -MeO -4-MePh 2093 Me NHCH (Et)CH 2 OMe 2 -MeO -4 -MePh 2094 Me N(c-Pr)CH 2 CH 2 CN 2 -MeO -4 -MePh 2095 Me NEt 2 2 -MeO -4 -MePh 2 096 Me NH-3-pentyl 2-MeO-4 -MePh 2 097 Me NHCH (Et) CH2CH 2 OMe 2-MeO-4-MePh 098 Me NHCH (Me) CH2CH 2 OMe 2 -MeO -4 -MePh 2 099 Me NHCH(CH 2 OMe) 2 2 -MeO -4 -MePh 2100 Me N(CH 2 CH2θMe ) 2 2 -MeO -4 -MePh 2101 Me NHCH(Et)CH2θMe 2 -MeO-4 -MePh 2102 Me N(c-Pr)CH 2 CH 2 CN 2 -MeO-4 -MePh 2103 Me NEt 2 2 -MeO-4-MePh 2104 Me NH-3-pentyl 2 -MeO -4 -MePh 2105 Me NHCH (Et)CH 2 CH 2 OMe 2 -MeO-4-MePh 2106 Me NHCH (Me) CH 2 CH 2 OMe 2 -MeO - -MePh 2107 Me NHCH(CH 2 OMe) 2 2-MeO-4-ClPh 2 108 Me N(CH 2 CH 2 OMe) 2 2-MeO-4-ClPh 2 109 Me NHCH(Et)CH OMe 2-MeO-4-ClPh 2110 Me N(c-Pr)CH CH 2 CN 2-MeO-4-ClPh 2111 Me NEt 2 2-MeO-4-ClPh 2112 Me NH-3 -pentyl 2-MeO-4-ClPh 2113 Me NHCH (Et)CH 2 CH OMe 2 -MeO-4-ClPh 2114 Me NHCH(Me)CH CH 2 OMe 2 -MeO-4-ClPh 2115 Cl N(CH 2 CH2θMe) 2 2 ,4-Cl 2 -Ph 2116 Cl N(Bu) Et 2 ,4-Cl 2 -Ph -157- 2117 Cl NHCH(Et)CH 2 OMe 2 ,4-Cl 2 -Ph 2118 Cl N(Pr)CH 2 CH 2 CN 2,4-Cl 2 -Ph 2119 Cl NH-3-pentyl 2 ,4-Cl 2 -Ph 2120 Cl NHCH (CH2OMe) _ 2 ,4-Cl 2 -Ph 2121 Cl NHCH(Et) 2 ,4-Me 2 -Ph 2122 Cl NHCH (CH 2 OMe) 2 2 ,4-Me 2 -Ph 2123 Cl N(CH 2 CH 2 OMe) 2 2 ,4-Me -Ph 2124 Cl N(c-Pr)CH 2 CH 2 CN 2,4-Me 2 -Ph 2125 Cl N(CH 2 CH 2 OMe) 2 2 -Cl, 4 -MePh 21 2 6 Cl NHCH ( CH 2 OMe ) 2 2 -Cl, 4 -MePh 2127 Cl NHCH(Et) 2 -Cl, 4 -MePh 21 2 8 Cl NEt 2 2,4-Me 2 -Ph 2 1 2 9 Cl N(Pr)CH 2 CH 2 CN 2 ,4-Me 2 -Ph 130 Cl N(Bu)CH2CH2CN 2 ,4-Me -Ph 2131 Cl NHCH(Et)CH2θMe 2 ,4-Me 2 -Ph 213 2 Cl NHCH ( Et ) 2 2 -Me, 4 -MeOPh 2 133 Cl NHCH ( CH2θMe ) 2 2 -Me, 4 -MeOPh 74 - 76 2 134 Cl N(CH2CH2θMe ) 2 2-Me, 4-MeOPh 2 135 Cl (S) -NHCH(CH 2 CH2θMe) - 2 -Me, 4-MeOPh 2 136 (CH 2 OMe) 2137 Cl (S) -NHCH (CH 2 CH2OMe) - 2,4-Me 2 -Ph 138 (CH 2 OMe) 139 Cl N(CH 2 CH 2 OMe ) 2 2 -Me,4-ClPh 2 140 Cl NHEt 2 ,4-Me 2 -Ph 2141 Cl NHCH(Et) 2 2 -Me,4-ClPh 2142 Cl NHCH (CH2OMe ) 2 2 -Me,4-ClPh 2143 Cl N(Ac)Et 2 ,4-Me -Ph 2144 Cl (S) -NHCH (CH 2 CH 2 OMe) - 2 -Me,4-ClPh 2145 (CH 2 OMe) 2146 Cl N(Pr)CH 2 CH 2 CN 2 -Me, 4-MeOPh 2147 Cl NEt 2 2 -Me, 4 -MeOPh -158 - 2 148 Cl (S) -NHCH (CH 2 CH 2 OMe) - 2 -Cl, 4 -MePh 2 149 (CH 2 OMe) 2150 Cl NEt 2 2 -Cl, 4-MePh 2151 Cl N(c-Pr)CH 2 CH2CN 2 -Me, 4 -MeOPh 2 152 Cl N(c-Pr)CH 2 CH 2 CN 2 -Cl, 4 -MePh 2153 Cl NHCH (Et)CH 2 OMe 2 -Me, 4 -MeOPh 2 154 Cl NHCH(Et)CH 2 OMe 2-Cl,4-MePh 2 155 Cl NHCH ( CH 2 OMe)2 2-Cl-4-MeOPh 2 156 Cl N(CH 2 CH 2 OMe ) 2 2 -Cl-4-MeOPh 2 157 Cl NHCH (Et)CH 2 OMe 2 -Cl-4 -MeOPh 2 158 Cl N(c-Pr)CH 2 CH 2 CN 2 -Cl-4-MeOPh 159 Cl NEt 2 2 -Cl-4-MeOPh 2 160 Cl NH-3-pentyl 2 -Cl-4 -MeOPh 2161 Cl NHCH (Et) CH 2 CH OMe 2 -Cl-4 -MeOPh 216 2 Cl NHCH (Me) CH 2 CH 2 OMe 2 -cl-4 -MeOPh 2163 Cl NHCH (Et) CH CH2OMe 2 -Br-4 -MeOPh 2 164 Cl NHCH (Me) CH 2 CH 2 OMe 2-Br-4-MeOPh 2165 Cl NHCH (Et) CH CH OMe 2-Me-4-MeOPh 2166 Cl NHCH (Me) CH 2 CH 2 OMe 2 -Me-4 -MeOPh 2 167 Cl NHCH ( CH 2 OMe ) 2 2 - -Cl-4, 5- (MeO) 2 Ph 2 168 Cl N ( CH2CH 2 OMe ) 2 2 - -Cl-4, 5- (MeO) 2 2 169 Cl NHCH(Et)CH 2 OMe 2 - -Cl-4, 5- (MeO)2Ph 170 Cl N(c-Pr)CH 2 CH2CN 2 - -Cl-4, 5- (MeO) 2 Ph 2171 Cl NEt2 2- -Cl-4, 5- (MeO) Ph 2172 Cl NH-3-pentyl 2 -Cl-4, 5- (MeO) 2 Ph 2173 Cl NHCH(Et)CH 2 CH 2 OMe 2- -Cl-4, 5- (MeO)2P 2174 Cl NHCH (Me) CH CH 2 OMe 2 -Cl-4, 5- (MeO)2P 2 175 Cl NHCH ( CH 2 OMe>2 2 -Br-4,5- (MeO)2Ph 176 Cl N(CH CH 2 OMe) 2 2 -Br-4,5- (MeO)2Ph 177 Cl NHCH(Et)CH 2 OMe 2 -Br-4,5- (MeO)2Ph 2 178 Cl N(c-Pr)CH 2 CH 2 CN 2 -Br-4,5- (MeO)2 2 179 Cl NEt 2 2 -Br-4,5- (MeO)2Ph 159 2 180 Cl NH-3 -pentyl 2 -Br-4,5- (MeO) 2 Ph 2181 Cl NHCH (Et ) CH 2 CH 2 OMe 2 -Br-4,5- (MeO) Ph 2 18 2 Cl NHCH (Me) CH 2 CH 2 OMe 2 -Br-4,5- (MeO) 2 Ph 2 183 Cl NHCH(CH 2 OMe) 2 2-C1-4, 6- (MeO) 2 Ph 2 184 Cl N(CH 2 CH 2 OMe) 2 2-Cl-4,6- (MeO) 185 Cl NHCH(Et)CH 2 OMe 2-Cl-4,6- (MeO) 2 Ph 2186 Cl N(c-Pr)CH 2 CH 2 CN 2-Cl-4,6- (MeO) 2 Ph 2187 Cl NEt 2 2-Cl-4,6- (MeO) 2 Ph 2188 Cl NH-3-pentyl 2-Cl-4,6- (MeO) Ph 2189 Cl NHCH(Et) CH 2 CH 2 OMe 2-Cl-4,6- (MeO) Ph 2 190 Cl NHCH (Me) CH 2 CH 2 OMe 2-Cl-4,6- (MeO) Ph 2191 Cl NHCH ( CH 2 OMe) 2 2-Me-4,6- (MeO) 2 Ph 2192 Cl N(CH 2 CH OMe ) 2 2 -Me-4,6- (MeO) 2 Ph 2193 Cl NHCH(Et)CH2θMe 2 -Me-4,6- (MeO) 2 Ph 2194 Cl N(c-Pr)CH 2 CH2CN 2-Me-4, 6- (MeO) Ph 2195 Cl NEt 2 2-Me-4,6- (MeO) 2Ph 2196 Cl NH-3-pentyl 2-Me-4,6- (MeO)2 2197 Cl NHCH (Et) CH 2 CH 2 OMe 2-Me-4, 6- (MeO) 2 Ph 2198 Cl NHCH (Me) CH 2 CH2OMe 2-Me-4,6- (MeO) Ph 2199 Cl N(c-Pr)CH 2 CH CN 2 -Br-4,6- (MeO) 2 Ph 2200 Cl NEt 2 2 -Br-4,6- (MeO) 2 Ph 2201 Cl NH-3-pentyl 2 -Br-4,6- (MeO) 2 Ph 2202 Cl NHCH(Et) CH 2 CH 2 OMe 2 -Br-4,6- (MeO)2Ph 2203 Cl NHCH (Me) CH 2 CH 2 OMe 2 -Br-4,6- (MeO)2Ph 2204 Cl NHCH (Et)CH 2 CH2OMe 2 -Me-4 -MeOPh 22 05 Cl NHCH (Me) CH CH OMe 2 -Me-4 -MeOPh 22 06 Cl NHCH(CH 2 OMe) 2 2 -MeO-4-MePh 2 07 Cl N(CH 2 CH 2 OMe) 2 2- Me o-4-MePh 2 08 Cl NHCH (Et)CH 2 OMe 2 -MeO-4-MePh 2 209 Cl N(c-Pr)CH 2 CH 2 CN 2 -MeO-4-MePh 2210 Cl NEt 2 2-MeO-4-MePh 2211 Cl NH-3-pentyl 2 -MeO-4-MePh 160 - 22 1 2 Cl NHCH (Et) CH 2 CH 2 OMe 2-MeO-4 -MePh 2 13 Cl NHCH (Me) CH 2 CH 2 OMe 2 -Me0-4-MePh 22 14 Cl NHCH (CH OMe) 2 2 -MeO-4-MePh 22 15 Cl N(CH 2 CH 2 OMe) 2 2-MeO-4-MePh 2 216 Cl NHCH (Et)CH 2 OMe 2-MeO-4-MePh 2217 Cl N(c-Pr)CH 2 CH 2 CN 2-MeO-4-MePh 2218 Cl NEt 2 2-MeO-4-MePh 2 19 Cl NH-3-pentyl 2 -MeO-4 -MePh 2220 Cl NHCH (Et) CH 2 CH OMe 2-MeO-4-MePh 2221 Cl NHCH (Me) CH2CH 2 OMe 2 -MeO -4 -MePh 2222 Cl NHCH(CH 2 OMe)2 2-MeO-4-ClPh 2223 Cl N(CH2CH 2 OMe)2 2-MeO-4-ClPh 2224 Cl NHCH (Et)CH 2 OMe 2-MeO-4-ClPh 222 5 Cl N(c-Pr)CH 2 CH 2 CN 2-MeO-4-ClPh 2 26 Cl NEt 2 2-MeO-4-ClPh 2 2 7 Cl NH-3-pentyl 2 -MeO-4-ClPh 2 228 Cl NHCH (Et) CH 2 CH2OMe 2 -MeO-4-ClPh 2 2 9 Cl NHCH (Me) CH2CH2θMe -MeO-4-ClPh 2 2 30 F N ( CH 2 CH 2 OMe>2 2 ,4-Cl 2 -Ph 2231 F N(Bu)Et ' 2,4-Cl 2 -Ph 223 2 F NHCH(Et)CH2θMe 2 ,4-Cl 2 -Ph 2233 F N(Pr)CH2CH 2 CN 2 ,4-Cl -Ph 2234 F NH-3-pentyl 2,4-Cl 2 -Ph 2235 F NHCH ( CH OMe ) 2 2 ,4-Cl 2 -Ph 2236 F NHCH ( Et ) 2 2,4-Me 2 -Ph 2237 F NHCH ( CH2θMe ) ,4-Me 2 -Ph 2238 F N ( CH 2 CH 2 OMe ) 2 2 ,4-Me -Ph 22 39 F N(c-Pr)CH 2 CH2CN 2,4-Me 2 -Ph 22 40 F N ( CH CH2θMe>2 2 -Cl,4-MePh 22 41 F NHCH ( CH2θMe ) 2 2 -Cl, 4 -MePh 2 242 F NHCH ( Et>2 2 -Cl, 4 -MePh 2243 F NEt2 2,4-Me 2 -Ph •161- 22 44 F N(Pr)CH 2 CH 2 CN 2 ,4-Me 2 -Ph 22 45 F N(Bu)CH 2 CH 2 CN 2,4-Me 2 -Ph 22 46 F NHCH(Et)CH 2 OMe 2,4-Me2-Ph 2247 F NHCH ( Et ) 2 2 -Me-4 -MeOPh 2248 F NHCH(CH2θMe ) 2 2-Me-4 -MeOPh 2249 F N(CH 2 CH2θMe ) 2 2 -Me-4 -MeOPh 2250 F (S) -NHCH (CH 2 CH 2 OMe) 2-Me-4-MeOPh 2251 (CH 2 OMe) 2252 F (S) -NHCH(CH 2 CH2θMe) 2,4-Me 2 -Ph 2253 (CH 2 OMe) 2254 F N(CH 2 CH 2 OMe) 2 2-Me,4-ClPh 2255 F NHEt 2 ,4-Me 2 -Ph 2256 F NHCH ( Et) 2 2-Me,4-ClPh 2257 F NHCH ( CH2θMe)2 2-Me,4-ClPh 2258 F N(Ac)Et 2,4-Me -Ph 2259 F (S) -NHCH (CH 2 CH 2 OMe) 2-Me,4-ClPh 2260 (CH 2 OMe) 2261 F N(Pr)CH CH2CN 2 -Me, 4 -MeOPh 2262 F NEt 2 2 -Me, 4 -MeOPh 2263 F (S) -NHCH(CH 2 CH 2 OMe) 2-Cl, 4 -MePh 2264 (CH 2 OMe) 2265 F NEt 2 2-Cl ,4 -MePh 2266 F N(c-Pr)CH 2 CH 2 CN 2 -Me, 4 -MeOPh 2267 F N(c-Pr)CH 2 CH2CN 2-Cl ,4 -MePh 2268 F NHCH(Et)CH2θMe 2 -Me, 4 -MeOPh 2269 F NHCH(Et)CH2θMe 2 -Cl , -MePh 22 70 F NHCH (CH2OMe) 2 2-C1- -4 -MeOPh 2271 F N(CH 2 CH 2 OMe) 2-C1- ■4 -MeOPh 2272 F NHCH(Et)CH 2 OMe 2-C1- ■ 4 -MeOPh 2273 F N(c-Pr)CH 2 CH 2 CN 2-C1- -4 -MeOPh 2274 F NEt 2 2-C1- ■ 4 -MeOPh 2275 F NH-3-pentyl 2-C1- -4 -MeOPh -162- 22 76 F NHCH (Et) CH 2 CH 2 OMe 2-C1-4-MeOPh 2211 F NHCH (Me) CH 2 CH 2 OMe 2-C1-4- MeOPh 2218 F NHCH (Et) CH 2 CH 2 OMe 2-Br-4- MeOPh 2219 F NHCH (Me) CH2CH OMe 2-Br-4-•MeOPh 22 80 F NHCH (Et) CH 2 CH 2 OMe 2-Me-4-■MeOPh 22 81 F NHCH (Me) C--2CH 2 OMe 2-Me-4-•MeOPh 2 282 F NHCH (CH 2 OMe) 2 2-Cl-4,5- !MeO) 2 Ph 2283 F N(CH 2 CH 2 OMe)2 2-Cl-4,5- MeO) Ph 2284 F NHCH(Et)CH 2 OMe 2-Cl-4,5- MeO) 2 Ph 2285 F N(c-Pr)CH 2 CH 2 CN 2-Cl-4,5- MeO) 2 Ph 2286 F NEt 2 2-Cl-4,5- MeO) 2 Ph 2287 F NH-3-pentyl 2-Cl-4,5- MeO) 2 Ph 2288 F NHCH(Et) CH 2 CH 2 OMe 2-Cl-4,5- MeO) 2 Ph 2289 F NHCH (Me) CH 2 CH 2 OMe 2-Cl-4,5- MeO) 2 Ph 2290 F NHCH(CH 2 OMe ) 2 -Br-4,5- MeO) 2P 2291 F N ( C--2CH 2 OMe ) 2 2 -Br-4,5- !MeO) 2Ph 22 9 2 F NHCH (Et)CH 2 OMe 2 -Br-4,5- MeO) 2P 2 93 F N(c-Pr)CH CH CN 2 -Br-4,5- MeO) 2 Ph 22 94 F NEt 2 2 -Br-4,5- MeO) 2 Ph 22 95 F NH-3-pentyl 2 -Br-4,5- MeO) 2 Ph 2 96 F NHCH(Et)CH 2 CH 2 OMe 2 -Br-4,5- !MeO) 2 Ph 2291 F NHCH(Me) CH 2 CH 2 OMe 2 -Br-4,5- MeO) 2P 22 98 F NHCH(CH 2 OMe>2 2-Cl-4,6- MeO) 2 Ph 22 99 F N ( CH 2 CH 2 OMe ) 2 2-Cl-4,6- MeO)2Ph 2 300 F NHCH(Et)CH 2 OMe 2-Cl-4,6- MeO) 2 Ph 2 301 F N(c-Pr)CH 2 CH 2 CN 2-Cl-4,6- MeO)2 30 2 F NEt 2 2-Cl-4,6- MeO)2Ph 2 303 F NH-3-pentyl 2-Cl-4,6- MeO)2Ph 2304 F NHCH(Et) CH 2 CH 2 OMe 2-C1-4.6- MeO)2P 2305 F NHCH (Me) CH2CH 2 OMe 2 -Cl-4,6- MeO)2Ph 2306 F NHCH ( CH 2 OMe ) 2 2-Me-4,6- MeO) 2Ph 2307 F N(O-2CH 2 0Me) 2 2-Me-4,6- MeO)2 -163 2 308 F NHCH (Et)CH 2 OMe 2-Me-4,6- (MeO) 2 Ph 309 F N(c-Pr)CH 2 CH 2 CN 2-Me-4,6- (MeO) 2 Ph 2 310 F NEt 2 2-Me-4,6- (MeO) 2 Ph 2311 F NH-3-pentyl 2-Me-4,6- (MeO) 2 Ph 2312 F NHCH (Et) CH 2 CH 2 OMe 2-Me-4,6- (MeO) 2 Ph 2313 F NHCH (Me) CH 2 CH 2 OMe 2-Me-4,6- (MeO) 2 Ph 2314 F N(c-Pr)CH 2 CH 2 CN 2-Br-4,6- (MeO) Ph 2315 F NEt2 2-Br-4,6- (MeO) 2 Ph 2316 F NH-3-pentyl 2 -Br-4,6- (MeO) 2 Ph 2317 F NHCH (Et) CH CH OMe 2-Br-4,6- (MeO) Ph 2318 F NHCH (Me) CH 2 CH2θMe 2-Br-4,6- (MeO) 2 Ph 2319 F NHCH (Et)CH2CH2OMe 2-Me-4 -MeOPh 2320 F NHCH (Me) CH2CH2OMe 2-Me-4 -MeOPh 2321 F NHCH (CH 2 OMe) 2 2 -MeO -4 -MePh 2322 F N(CH 2 CH2θMe>2 2 -MeO -4 -MePh 2323 F NHCH(Et)CH 2 OMe 2-MeO-4-MePh 23 2 4 F N(c-Pr)CH2CH2CN 2 -MeO -4 -MePh 2325 F NEt 2 2 -MeO -4 -MePh 2326 F NH-3-pentyl 2 -MeO -4 -MePh 2327 F NHCH (Et) CH 2 CH2θMe 2 -MeO -4 -MePh 2328 F NHCH (Me) CH CH OMe 2 -MeO -4 -MePh 2329 F NHCH(CH 2 OMe) 2 2 -MeO -4 -MePh 2330 F N ( CH2CH2θMe ) 2 2-MeO-4-MePh 2331 F NHCH (Et)CH 2 OMe 2 -MeO -4 -MePh 2332 F N(c-Pr)CH2CH2CN 2 -MeO -4 -MePh 2333 F NEt 2 2 -MeO -4 -MePh 2334 F NH-3-pentyl 2 -MeO -4 -MePh 2 335 F NHCH (Et) CH2CH2θMe 2 -MeO -4 -MePh 2 336 F NHCH (Me) CH 2 CH 2 OMe 2 -MeO -4 -MePh 2 337 F NHCH(CH 2 OMe) 2 2 -MeO-4-ClPh 2 338 F N(CH 2 CH 2 OMe ) 2 2-MeO-4-ClPh 2 339 F NHCH(Et)CH 2 OMe 2 -MeO-4-ClPh -164- 2340 F N(c-Pr)CH 2 CH 2 CN 2-Me0-4-ClPh 2341 F NEt2 2-MeO-4-ClPh 2342 F NH-3-pentyl 2-MeO-4-ClPh 2343 F NHCH(Et) CH2CH 2 OMe 2-MeO-4-ClPh 2 344 F NHCH (Me) CH 2 CH2OMe 2-MeO-4-ClPh 2 345 Me NMe(CH2CH 2 OMe) 2,4-Cl 2 -Ph 2 346 Me NEt (CH2CH2θMe) 2,4-Cl 2 -Ph 2 347 Me NPr(CH 2 CH 2 OMe) 2 ,4-Cl 2 -Ph 2348 Me NH-2 -butyl 2 ,4-Cl 2 -Ph 2349 Me cyclobutylamino 2 ,4-Cl -Ph 2350 Me 2 -ethylpiperidinyl 2 ,4-Cl 2 -Ph 2351 Me NMe (propargyl) 2 ,4-Cl 2 -Ph 2352 Me NEt (propargyl) 2 ,4-Cl 2 -Ph 2353 Me NEtMe 2 ,4-Cl 2 -Ph 2354 Me NEtPr 2 ,4-Cl 2 -Ph 2355 Me NMeBu 2 ,4-Cl 2 -Ph 2356 Me NMe(CH 2 cPr) 2 ,4-Cl 2 -Ph 2357 Me NEt (CH2cPr) 2 ,4-Cl 2 -Ph 2358 Me NPr(CH 2 cPr) 2 ,4-Cl 2 -Ph 2359 Me NMe (CH 2 CH 2 OMe) 2-Me-4 -MeOPh 2360 Me NEt (CH 2 CH2θMe) 2-Me-4 -MeOPh 2361 Me NPr(CH2CH2θMe) 2 -Me-4 -MeOPh 2362 Me NH-2 -butyl 2-Me-4-MeOPh 2363 Me cyclobutylamino 2-Me-4-MeOPh 2364 Me 2 -ethylpiperidinyl 2-Me-4-MeOPh 2365 Me NMe (propargyl) 2 -Me-4 -MeOPh 2366 Me NEt (propargyl) 2-Me-4-MeOPh 2367 Me NEtMe 2 -Me-4-MeOPh 2368 Me NEtPr 2-Me-4-MeOPh 2360 Me NMeBu 2 -Me-4 -MeOPh 2370 Me NMe (CH 2 cPr) 2-Me-4-MeOPh 2371 Me NEt (CH2CPr) 2-Me-4-MeOPh 2372 Me NPr (CH 2 cPr) 2-Me-4-MeOPh -165 - 2373 Me NMe(CH CH 2 OMe) 2 ,4-Me 2 -Ph 2374 Me NEt (CH 2 CH 2 OMe) 2 ,4-Me -Ph 2375 Me NPr(CH 2 CH 2 OMe) 2,4-Me 2 -Ph 2376 Me NH- 2 -butyl 2,4-Me 2 -Ph 2377 Me cyclobutylamino 2,4-Me 2 -Ph 2378 Me 2 -ethylpiperidinyl 2,4-Me 2 -Ph 2379 Me NMe (propargyl) 2 ,4-Me 2 -Ph 2380 Me NEt (propargyl) 2 ,4-Me 2 -Ph 2 381 Me NEtMe 2 ,4-Me 2 -Ph 2 382 Me NEtPr 2 ,4-Me 2 -Ph 2383 Me NMeBu 2 ,4-Me 2 -Ph 2384 Me NMe(CH 2 cPr) 2 ,4-Me 2 -Ph 2385 Me NEt (CH 2 cPr) 2 ,4-Me 2 -Ph 2386 Me NPr(CH 2 cPr) 2,4-Me -Ph 2 387 Me NMe(CH 2 CH2θMe) 2 -Cl-4 -MeOPh 2388 Me NEt (CH2CH2θMe) 2-ci-4-MeOPh 2389 Me NPr(CH 2 CH2θMe) 2 -Cl-4 -MeOPh 2390 Me NH-2 -butyl -ci-4-MeOPh 2391 Me cyclobutylamino 2 -cl-4 -MeOPh 2392 Me -ethylpiperidinyl 2 -Cl-4 -MeOPh 2393 Me NMe (propargyl) 2 -Cl-4-MeOPh 2394 Me NEt (propargyl) 2_ci-4-MeOPh 2395 Me NEtMe 2 -Cl-4-MeOPh 2396 Me NEtPr 2 -ci-4-MeOPh 2397 Me NMeBu 2 -Cl-4 -MeOPh 2398 Me NMe(CH cPr) 2 -Cl-4 -MeOPh 2399 Me NEt(CH2CPr) 2 -ci-4-MeOPh 2400 Me NPr (CH2CPr) 2 -cl-4-MeOPh 2401 Me NMe (CH 2 CH2θMe) ,5-Me 2 -4-MeOPh 2402 Me NEt (CH 2 CH 2 OMe) ,5-Me 2 -4-MeOPh 2403 Me NPr (CH 2 CH 2 OMe) 2 ,5-Me -4-MeOPh 2404 Me NH- 2 -butyl 2 ,5-Me 2 -4-MeOPh 166 2405 Me cyclobutylamino 2,5-Mβ2-4-MeOPh 2406 Me 2 -ethylpiperidinyl 2,5-Me 2 -4-MeOPh 2407 Me NMe (propargyl) 2,5-Me 2 -4-MeOPh 2408 Me NEt (propargyl) 2,5-Me -4-MeOPh 2409 Me NEtMe 2,5-Me 2 -4-MeOPh 2410 Me NEtPr 2,5-Me 2 -4-MeOPh 2411 Me NMeBu 2,5-Me 2 -4-MeOPh 2412 Me NMe (CH 2 cPr) 2,5-Me 2 -4-MeOPh 2413 Me NEt (CH 2 cPr) 2,5-Me -4-MeOPh 2414 Me NPr(CH cPr) 2, 5-Me 2 -4-MeOPh 2415 Cl NMe (CH CH 2 OMe) 2,4-Cl 2 -Ph 2416 Cl NEt (CH 2 CH 2 OMe) 2,4-Cl 2 -Ph 2417 Cl NPr(CH 2 CH 2 OMe) 2,4-Cl 2 -Ph 2418 Cl NH-2 -butyl 2,4-Cl 2 -Ph 2419 Cl cyclobutylamino 2,4-Cl 2 -Ph 2420 Cl 2 -ethylpiperidinyl 2,4-Cl 2 -Ph 2421 Cl NMe (propargyl) 2,4-Cl 2 -Ph 2422 Cl NE (propargyl) 2,4-Cl 2 -Ph 2423 Cl NEtMe 2,4-Cl 2 -Ph 2424 Cl NEtPr 2,4-Cl 2 -Ph 2425 Cl NMeBu 2,4-Cl 2 -Ph 2426 Cl NMe (CH 2 cPr) 2,4-Cl -Ph 2427 Cl NE (CH cPr) 2,4-Cl 2 -Ph 2428 Cl NPr (CH 2 cPr) 2,4-Cl -Ph 24 9 Cl NMe(CH 2 CH 2 OMe) 2 -Me-4 -MeOPh 2 430 Cl NEt (CH 2 CH 2 OMe) 2-Me-4-MeOPh 2 431 Cl NPr(CH 2 CH 2 OMe) 2 -Me-4 -MeOPh 2 43 2 Cl NH-2-butyl 2-Me-4-MeOPh 433 Cl cyclobutylamino 2 -Me-4 -MeOPh 2434 Cl 2 -ethylpiperidinyl 2-Me-4-MeOPh 2435 Cl NMe (propargyl) 2-Me-4-MeOPh 2436 Cl NEt (propargyl) 2-Me-4-MeOPh -167- 2437 Cl NEtMe 2-Me-4-MeOPh 2438 Cl NEtPr 2-Me-4-MeOPh 2439 Cl NMeBu 2 -Me-4 -MeOPh 2440 Cl NMe(CH 2 cPr) 2 -Me-4 -MeOPh 2441 Cl NEt (CH 2 cPr) -Me-4 -MeOPh 2442 Cl NPr(CH 2 cPr) 2 -Me-4 -MeOPh 2443 Cl NMe(CH 2 CH2θMe) 2,4-Me 2 -Ph 2444 Cl NEt (CH 2 CH 2 OMe) 2,4-Me 2 -Ph 2445 Cl NPr (CH 2 CH 2 OMe) 2,4-Me -Ph 2446 Cl NH- 2 -butyl ,4-Me 2 -Ph 2 447 Cl cyclobutylamino 2,4-Me -Ph 2 448 Cl 2 -ethylpiperidinyl 2,4-Me 2 -Ph 2 449 Cl NMe (propargyl) 2 ,4-Me 2 -Ph 2 450 Cl NEt (propargyl) 2 ,4-Me 2 -Ph 2 451 Cl NEtMe 2 ,4-Me -Ph 2452 Cl NEtPr 2,4-Me 2 -Ph 2 453 Cl NMeBu 2 ,4-Me 2 -Ph 2 454 Cl NMe(CH2CPr) 2 ,4-Me -Ph 2 455 Cl NEt (CH2CPr) 2 ,4-Me 2 -Ph 2 456 Cl NPr(CH2cPr) 2 ,4-Me 2 -Ph 2 457 Cl NMe(CH 2 CH 2 OMe) 2 -ci-4-MeOPh 2 458 Cl NEt (CH 2 CH2θMe) -Cl-4-MeOPh 2 459 Cl NPr(CH 2 CH 2 OMe) 2 -Cl-4 -MeOPh 2 460 Cl NH-2 -butyl 2 -Cl-4 -MeOPh 461 Cl cyclobutylamino 2 -cl-4 -MeOPh 2 462 Cl 2 -ethylpiperidinyl 2 -cl-4 -MeOPh 2463 Cl NMe (propargyl) 2-Cl-4-MeOPh 2464 Cl NEt (propargyl) 2 -cl-4 -MeOPh 2465 Cl NEtMe 2 -Cl-4 -MeOPh 2466 Cl NEtPr 2 -Cl-4 -MeOPh 2467 Cl NMeBu 2-Cl-4-MeOPh 2468 Cl NMe (CH 2 cPr) 2 -Cl-4-MeOPh 2469 Cl NEt (CH 2 cPr) 2-Cl-4-MeOPh - 168 - 2470 Cl NPr (CH 2 cPr) 2 -Cl-4 -MeOPh 2471 Cl NMe(CH 2 CH2θMe) 2,5-Me2-4-MeOPh 2472 Cl NEt (CH CH2θMe) 2,5-Me 2 -4-MeOPh 2473 Cl NPr(CH 2 CH2θMe) 2 ,5-Me 2 -4-MeOPh 2 474 Cl NH- 2 -butyl 2 ,5-Me -4-MeOPh 2 475 Cl cyclobutylamino 2 ,5-Me -4-MeOPh 476 Cl 2 -ethylpiperidinyl 2 ,5-Me -4-MeOPh 2 477 Cl NMe (propargyl) 2,5-Me 2 -4-MeOPh 2 478 Cl NEt (propargyl) 2 ,5-Me -4-MeOPh 2 479 Cl NEtMe 2 ,5-Me 2 -4-MeOPh 2480 Cl NEtPr 2 ,5-Me 2 -4-MeOPh 2481 Cl NMeBu 2 ,5-Me 2 -4-MeOPh 2482 Cl NMe(CH 2 cPr) 2 ,5-Me -4-MeOPh 2483 Cl NEt (CH 2 cPr) 2,5-Me 2 -4-MeOPh 2484 Cl NPr(CH 2 cPr) 2,5-Mβ2-4-MeOPh 2485 F NMe(CH 2 CH2θMe) 2,4-Cl 2 -Ph 2486 F NEt (CH 2 CH2θMe) 2,4-Cl 2 -Ph 2487 F NPr(CH2CH2θMe) 2,4-Cl 2 -Ph 2488 F NH- 2 -butyl 2 ,4-Cl 2 -Ph 2489 F cyclobutylamino ,4-Cl 2 -Ph 2490 F 2 -ethylpiperidinyl 2 ,4-Cl 2 -Ph 2491 F NMe (propargyl) 2 ,4-Cl -Ph 2492 F NEt (propargyl) 2 ,4-Cl 2 -Ph 2493 F NEtMe 2,4-Cl 2 -Ph 2494 F NEtPr 2,4-Cl 2 -Ph 2495 F NMeBu 2,4-Cl 2 -Ph 2496 F NMe(CH 2 cPr) 2 ,4-Cl 2 -Ph 2497 F NEt (CH2CPr) 2 ,4-Cl -Ph 2498 F NPr(CH2CPr) 2 ,4-Cl 2 -Ph 2 499 F NMe(CH2CH2θMe) 2 -Me -4 -MeOPh 2 500 F NEt (CH 2 CH2θMe) 2-Me-4 -MeOPh 2 501 F NPr (CH2CH2θMe) 2-Me- -MeOPh -169- 50 2 F NH-2 -butyl 2-Me-4 -MeOPh 2 503 F cyclobutylamino 2 -Me-4 -MeOPh 2504 F 2 -ethylpiperidinyl 2 -Me-4 -MeOPh 2505 F NMe (propargyl) 2 -Me-4 -MeOPh 2506 F NEt (propargyl) 2 -Me-4 -MeOPh 2507 F NEtMe 2-Me-4-MeOPh 2508 F NEtPr 2 -Me-4 -MeOPh 2509 F NMeBu 2 -Me- -MeOPh 2510 F NMe (CH cPr) 2-Me-4 -MeOPh 2511 F NEt (CH 2 cPr) 2-Me-4 -MeOPh 2512 F NPr(CH 2 cPr) 2 -Me-4 -MeOPh 2513 F NMe(CH 2 CH OMe) 2 ,4-Me -Ph 2514 F NE (CH 2 CH 2 OMe) 2,4-Me 2 -Ph 2515 F NPr(CH CH 2 OMe) ,4-Me 2 -Ph 2516 F NH- 2 -butyl 2 ,4-Me -Ph 2517 F cyclobutylamino 2 ,4-Me 2 -Ph 2518 F 2 -ethylpiperidinyl 2 ,4-Me 2 -Ph 2519 F NMe (propargyl) 2 ,4-Me 2 -Ph 2520 F NEt (propargyl) 2 ,4-Me 2 -Ph 2521 F NEtMe ,4-Me -Ph 2522 F NEtPr 2 ,4-Me -Ph 25->3 F NMeBu 2 ,4-Me 2 -Ph 2 524 F NMe (CH 2 cPr) 2 ,4-Me 2 -Ph 5 2 5 F NEt (CH2cPr) ,4-Me -Ph 2 5 2 6 F NPr (CH2CPr) 2,4-Me -Ph 2 5 2 7 F NMe(CH 2 CH 2 OMe) 2 -Cl-4 -MeOPh 2 5 2 8 F NEt (CH 2 CH 2 OMe) 2-Cl-4 -MeOPh 2 5 9 F NPr(CH 2 CH2θMe) 2 -Cl-4 -MeOPh 2530 F NH- -butyl 2 -Cl-4 -MeOPh 2531 F cyclobutylamino 2 -Cl-4 -MeOPh 2532 F 2 -ethylpiperidinyl 2 -Cl-4 -MeOPh 2533 F NMe (propargyl) 2 -Cl-4 -MeOPh 2534 F NEt (propargyl) 2 -Cl-4 -MeOPh -170- 2 535 F NEtMe 2-Cl-4-MeOPh 2 536 F NEtPr 2 -Cl-4 -MeOPh 2537 F NMeBu 2 -Cl-4 -MeOPh 2538 F NMe(CH 2 cPr) 2-Cl-4-MeOPh 2539 F NEt (CH cPr) 2 -Cl-4 -MeOPh 2540 F NPr(CH 2 cPr) 2 -Cl-4 -MeOPh 2541 F NMe(CH 2 CH2θMe) ,5-Me 2 -4-MeOPh 2542 F NEt (CH2CH 2 OMe) 2,5-Mβ2-4-MeOPh 2543 F NPr(CH 2 CH2θMe) 2,5-Me 2 -4-MeOPh 2544 F NH- 2 -butyl 2 ,5-Me -4-MeOPh 2545 F cyclobutylamino 2 ,5-Me 2 -4-MeOPh 2546 F 2 -ethylpiperidinyl 2 ,5-Me 2 -4-MeOPh 2547 F NMe (propargyl) 2,5-Me 2 -4-MeOPh 2548 F NEt (propargyl) 2,5-Me -4-MeOPh 2549 F NEtMe 2 ,5-Me -4-MeOPh 2550 F NEtPr 2 ,5-Me -4-MeOPh 2551 F NMeBu 2 ,5-Me 2 -4-MeOPh 2552 F NMe(CH 2 cPr) 2,5-Me2-4-MeOPh 2 553 F NEt (CH 2 cPr) 2,5-Me -4-MeOPh 554 F NPr (CH2cPr) 2 ,5-Me -4-MeOPh a)CI-HRMS: Calcd: 367. 2 498; Found: 367. 2 468 (M + H) * b) CI-HRMS: Calcd: 387.195 2 ; Found: 387.1939 (M + H) * Utility CRF-Rl Receptor Binding Assay for the Evaluation of Biological Activity The following is a description of the isolation of cell membranes containing cloned human CRF-Rl receptors for use in the standard binding assay -171- as well as a description of the assay itself. Messenger RNA was isolated from human hippocampus. The mRΝA was reverse transcribed using oligo (dt) 12-18 and the coding region was amplified by PCR from start to stop codons The resulting PCR fragment was cloned into the EcoRV site of pGEMV, from whence the insert was reclaimed using Xhol + Xbal and cloned into the Xhol + Xbal sites of vector pm3ar ( which contains a CMV promoter, the SV40 't' splice and early poly A signals, an Epstein-Barr viral origin of replication, and a hygromycin selectable marker) . The resulting expression vector, called phchCRFR was transfected in 293EBΝA cells and cells retaining the episome were selected in the presence of 400 μM hygromycin. Cells surviving 4 weeks of selection in hygromycin were pooled, adapted to growth in suspension and used to generate membranes for the binding assay described below. Individual aliquots containing approximately 1 x 10^ of the suspended cells were then centrifuged to form a pellet and frozen. For the binding assay a frozen pellet described above containing 293EBNA cells transfected with hCRFRl receptors is homogenized in 10 ml of ice cold tissue buffer ( 50 mM HEPES buffer pH 7.0, containing 10 mM MgCl 2 , 2 mM EGTA, 1 μg/1 aprotinin, 1 μg/ml leupeptin and 1 μg/ml pepstatin) . The homogenate is centrifuged at 40,000 x g for 12 min and the resulting pellet rehomogenized in 10 ml of tissue buffer. After another centrifugation at 40,000 x g for 12 min, the pellet is resuspended to a protein concentration of 360 μg/ml to be used in the assay. Binding assays are performed in 96 well plates; each well having a 300 μl capacity. To each well is added 50 μl of test drug dilutions (final concentration -172- of drugs range from 10- 10 - 10- 5 M) , 100 μl of 125j._ ovine-CRF ( 125 I-o-CRF) (final concentration 150 pM) and 150 μl of the cell homogenate described above. Plates are then allowed to incubate at room temperature for 2 hours before filtering the incubate over GF/F filters (presoaked with 0.3% polyethyleneimine) using an appropriate cell harvester. Filters are rinsed 2 times with ice cold assay buffer before removing individual filters and assessing them for radioactivity on a gamma counter. Curves of the inhibition of 125 I-o-CRF binding to cell membranes at various dilutions of test drug are analyzed by the iterative curve fitting program LIGAND [P.J. Munson and D. Rodbard, Anal. Biochem. 107:220 (1980) , which provides Ki values for inhibition which are then used to assess biological activity. A compound is considered to be active if it has a Ki value of less than about 10000 nM for the inhibition of CRF. Inhibition of CRF-Stimulated Adenylate Cvclase Activity Inhibition of CRF- stimulated adenylate cyclase activity can be performed as described by G. Battaglia et al . Synapse 1:572 (1987). Briefly, assays are carried out at 37° C for 10 min in 200 ml of buffer containing 100 mM Tris-HCl (pH 7.4 at 37° C) , 10 mM MgCl 2 , 0.4 mM EGTA, 0.1% BSA, 1 mM isobutylmethylxanthine (IBMX) , 250 units/ml phosphocreatine kinase, 5 mM creatine phosphate, 100 mM guanosine 5 ' -triphosphate, 100 nM oCRF, antagonist peptides (concentration range 10 ~9 to 10 " 6m ) and 0.8 mg original wet weight tissue •173- (approximately 40-60 mg protein) . Reactions are initiated by the addition of 1 mM ATP/ 32 P]ATP (approximately 2-4 mCi/tube) and terminated by the addition of 100 ml of 50 mM Tris-HCL, 45 mM ATP and 2% sodium dodecyl sulfate. In order to monitor the recovery of cAMP, 1 μl of [ 3 H] cAMP (approximately 40,000 dpm) is added to each tube prior to separation. The separation of [ 32 P] cAMP from [ 32 P]ATP is performed by sequential elution over Dowex and alumina columns. In vivo Biological Assay The in vivo activity of the compounds of the present invention can be assessed using any one of the biological assays available and accepted within the art. Illustrative of these tests include the Acoustic Startle Assay, the Stair Climbing Test, and the Chronic Administration Assay. These and other models useful for the testing of compounds of the present invention have been outlined in CW. 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 disorders, and/or anxiety. Compounds of this invention can be administered to treat these abnormalities by means that produce contact of the active agent with the agent's site of action in the body of a mammal. The compounds can be -174- 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 -175- can also be administered parenterally in sterile liquid dose formulations. Gelatin capsules can be used to contain the active ingredient and a suitable carrier such as but not limited to lactose, starch, magnesium stearate, steric acid, or cellulose derivatives. Similar diluents can be used to make compressed tablets. Both tablets and capsules can be manufactured as sustained release products to provide for continuous release of medication over a period of time. Compressed tablets can be sugar-coated or film- coated to mask any unpleasant taste, or used to protect the active ingredients from the atmosphere, or to allow selective disintegration of the tablet in the gastrointestinal tract. Liquid dose forms for oral administration can contain coloring or flavoring agents to increase patient acceptance. In general, water, pharmaceutically acceptable oils, saline, aqueous dextrose (glucose), and related sugar solutions and glycols, such as propylene glycol or polyethylene glycol, are suitable carriers for parenteral solutions. Solutions for parenteral administration preferably contain a water soluble salt of the active ingredient, suitable stabilizing agents, and if necessary, butter substances. Antioxidizing agents, such as sodium bisulfite, sodium sulfite, or ascorbic acid, either alone or in combination, are suitable stabilizing agents. Also used are citric acid and its salts, and EDTA. In addition, parenteral solutions can contain preservatives such as benzalkonium chloride, methyl- or propyl-paraben, and chlorobutanol . Suitable pharmaceutical carriers are described -176- 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. -177- 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. -178-

Claims: CLAIMS WHAT IS CLAIMED IS: A compound of Formula (50) R 3 N N^ N N - C Λ Y CH^ R 4 R 4 R 4c FORMULA (50) and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt forms thereof, selected from the group: a compound of Formula (50) wherein R 3 is - NHCH (CH 2 CH 2 OMe) (CH 2 OMe) , R 4a i s Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is -NHCH(Et)2, R 4 is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is 2- ethylpiperid-1-yl, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is cyclobutyl- amino, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; -179- a compound of Formula (50) wherein R 3 is N(Me)CH CH=CH 2 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et)CH 2 CH=CH 2 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)CH 2 cPr, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et)CH 2 cPr, R 4a is Me, R b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Pr)CH cPr, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Pr, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Et- R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Bu, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N (Me) propargyl, R 4a i s Me, R 4b is H, R 4c is OMe, 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et) propargyl, R 4 i s Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(CH 3 )CH(CH 3 )CH 3 , R 4a is Me, R 4b is H, R 4c is -180- OMe R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is (CH CH 2 OMe) - CH 2 CH=CH 2 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH CH OMe)Me, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Et, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Pr, R 4a is M e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe) - CH 2 cPr, R a ig Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH ( CH 3 ) CH 2 CH 3 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(cPr) 2 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is 2- ethylpiperid-1-yl, R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is cyclobutylamino, R 4a ig Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)CH 2 CH=CH 2 , R 4 is M e, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; ■181- a compound of Formula (50) wherein R 3 is N(Et)CH 2 CH=CH , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)CH 2 cPr, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et)CH 2 cPr, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Pr)CH 2 cPr, R R 44aa iis Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Pr, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Et, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Bu, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N (Me) propargyl, R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et) propargyl, R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(CH 3 )CH(CH 3 )CH3, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH 2 CH 2 OMe) - CH 2 CH=CH 2 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is ■ 182- Me and R 4 e is H ; a compound of Formula (50) wherein R 3 is N ( CH 2 CH 2 OMe ) Me, R 4 is M e, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N ( CH 2 CH 2 OMe ) Et, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Pr, R 4a is Me , R 4b is H , R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH CH 2 OMe) - CH 2 cPr, R 4 i s Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH ( CH 3 ) CH 2 CH 3 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is -NHCH(Et) 2 , R R 44aa iis Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(cPr) 2 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is -NHCH(Et) 2 , R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is 2- ethylpiperid-1-yl, R 4a i s OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is cyclobutyl- amino, R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; -183- a compound of Formula (50) wherein R 3 is N ( Me ) CH 2 CH=CH 2 , R 4 is 0 Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N ( Et ) CH 2 CH=CH 2 , R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)CH2cPr R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et)CH 2 cPr R R 44aa iis OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Pr)CH cPr, R R 44aa iis OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Pr, R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Et, R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Bu, R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N (Me) propargyl, R 4a i s OMe, R b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et) propargyl, R 4a i s OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(CH 3 )CH(CH 3 )CH 3 , R 4a is OMe, R 4b is H, R c is OMe, R 4d is H and R 4e is H; -184- a compound of Formula (50) wherein R 3 is N ( CH 2 CH OMe ) - CH 2 CH=CH 2 , R i s OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H ; a compound of Formula (50) wherein R 3 is N ( CH 2 CH 2 OMe)Me, R is 0 Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H ; a compound of Formula (50 ) wherein R 3 is N ( CH 2 CH 2 OMe)Et, R 4a i s OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H ; a compound of Formula (50 ) wherein R 3 is N(CH 2 CH 2 OMe)Pr, R ia 0 Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H ; a compound of Formula (50) wherein R 3 is N ( CH 2 CH 2 OMe ) - CH 2 cPr, R 4 is OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50 ) wherein R 3 is NHCH ( CH 3) CH CH 3 , R 4 i s OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H ; a compound of Formula (50) wherein R 3 is NHCH ( cPr ) , R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N ( CH 2 CH 0Me ) 2 , R a is OMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH ( Et ) 2 , R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N ( Et ) 2 , R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H ; 0 a compound of Formula (50) wherein R 3 is 2- ethylpiperid-1-yl, R 4a is OMe, R 4b is H, R 4c is -185- OMe, R d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is cyclobutylamino, R 4a i s OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N ( Me)CH 2 CH=CH 2 , R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et)CH 2 CH=CH 2 , R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)CH 2 cPr, R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et)CH 2 cPr, R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Pr)CH 2 cPr, R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Pr, R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Et, R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Bu, R 4a is OMe, R 4b is H, R 4c is OMe, R 4 is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N (Me) propargyl, R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; ■186- a compound of Formula (50) wherein R 3 is N(Et) propargyl, R 4a i s 0 Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(CH 3 )CH(CH 3 )CH 3 , R a is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH 2 CH 2 OMe) - CH 2 CH=CH 2 , R 4 is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Me, R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Et, R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Pr, R 4a i s OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH 2 CH 2 OMe) - CH2cPr, R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(CH 3 )CH 2 CH 3 , R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(cPr)2, R 4a is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4 ^ is H ; a compound of Formula (50) wherein R 3 is N (CH2CH2θMe) 2 , R 4a is OMe, R b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(Et)2, R 4a -187- is OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et) 2 , R 4a i s OMe, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (50) wherein R 3 is 2- ethylpiperid-1-yl, R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is cyclobutylamino, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is N(Me)CH 2 CH=-CH 2/ R 4 is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is N(Et)CH 2 CH-=CH 2 , R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is N(Me)CH 2 cPr, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is N(Et)CH 2 cPr, R R 44aa iiss Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is N(Pr)CH 2 cPr, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is N(Me)Pr, R 4a is Me, R b is H, R 4c is OMe, R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is N(Me)Et, R 4a iiss Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is Me; -188- a compound of Formula (50) wherein R 3 .is N(Me)Bu R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is N (Me) propargyl, R a is Me , R 4 ig H/ R 4c ± g QMe ^ R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is N(Et ) propargyl, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is NHCH(CH 3 )CH(CH 3 )CH 3 , R 4a is Me , R 4b is H , R 4c is OMe, R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is N (CH 2 CH 2 OMe) - CH 2 CH=CH 2 , R 4 is Me, R 4b is H, R 4c is OMe, R 4d i . H and R 4e is Me; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Me, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Et, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Pr, R 4a is Me, R 4b is H, R 4c is OMe, R d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is N (CH CH 2 OMe) - CH 2 cPr, R 4a ig Me, R 4b is H, R 4c is OMe, R d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is NHCH(CH 3 )CH 2 CH 3 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is NHCH(Et) 2 , R 4a -189- is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is Me; compound of Formula (50) wherein R 3 is NHCH(cPr) 2 , R R 44aa iiss Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is Me; a compound of Formula (50) wherein R 3 is NHCH(Et) 2 R 4a iiss MM<e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is 2- ethylpiperid-1-yl, R 4a i s M e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is cyclobutylamino, R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(Me ) CH 2 CH=CH 2 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R e is OMe; a compound of Formula (50) wherein R 3 is N(Et)CH 2 CH=CH 2 , R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(Me)CH 2 cPr, R R 44aa iiss Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(Et)CH cPr, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe ; a compound of Formula (50) wherein R 3 is N(Pr)CH 2 cPr, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(Me)Pr, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; -190- a compound of Formula (50) wherein R 3 is N(Me)Et R 4a iiss NMe, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(Me)Bu R 4a iiss VM.e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N (Me) propargyl, R 4a i s M e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(Et) propargyl, R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is NHCH(CH 3 )CH(CH 3 )CH 3 , R 4a is M e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N (CH 2 CH 2 OMe) - CH 2 CH=CH 2 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Me, R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Et, R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Pr, R 4a i s M e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N (CH 2 CH 2 OMe) - CH 2 cPr, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is NHCH(CH 3 )CH 2 CH 3 , R 4a i s Me, R 4b is H, R 4c is OMe, -191- R 4d is H and R 4e is OMe ,- a compound of Formula (50) wherein R 3 is NHCH(cPr)2 R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N (CH 2 CH 2 OMe) 2 , R R 44aa iiss 1Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is NHCH(Et) 2 , R 4a iiss MM<e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(Et) 2 , R 4 ± s Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is NHCH(Et) 2 R 4a iiss CCl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is 2- ethylpiperid-1-yl, R 4a i s C l , R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe,- a compound of Formula (50) wherein R 3 is cyclobutylamino, R 4a is cl, R 4b is H, R 4c is OMe, R 4d is H and R e is OMe; a compound of Formula (50) wherein R 3 is N(Me)CH 2 CH=CH 2 , R a is cl , R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(Et)CH 2 CH=CH 2 R 4a is C l , R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(Me)CH 2 cPr R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4 is OMe; a compound of Formula (50) wherein R 3 is N(Et)CH 2 cPr, ■ 192- R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(Pr)CH 2 cPr, R R 44aa iiss Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(Me)Pr, R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(Me)Et, R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(Me)Bu, R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N (Me) propargyl, R 4a i s cl , R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(Et) propargyl, R 4a i s cl , R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is NHCH(CH 3 )CH(CH 3 )CH 3 , R 4a is C l , R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N (CH 2 CH 2 OMe) - CH 2 CH=CH 2 , R 4a 1S Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Me, R 4a 1S Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Et, R 4a 1S Cl , R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; ■193- a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Pr, R 4 is cl , R 4b is H, R 4c is OMe, -4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(CH 2 CH OMe) - CH 2 cPr, R 4 i s cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is NHCH(CH 3 )CH 2 CH 3 , R 4 is Cl , R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe,- a compound of Formula (50) wherein R 3 is NHCH(cPr) 2 R R 44aa iiss Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe,- a compound of Formula (50) wherein R 3 is N (CH CH 2 OMe) , R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is H and .R 4e is OMe; a compound of Formula (50) wherein R 3 is NHCH(Et) 2 , R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is OMe; a compound of Formula (50) wherein R 3 is N(Et) 2 , R 4a i s Cl, R 4b is H, R 4c is OMe, R 4d is H and R e is OMe; a compound of Formula (50) wherein R 3 is NHCH(Et) , R 4a iiss Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is 2- ethylpiperid-1-yl, R 4a i s cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is cyclobutylamino, R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)CH 2 CH=CH 2 , R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; -194- a compound of Formula (50) wherein R 3 is N ( Et ) CH 2 CH=CH 2 , R 4a is Cl, R 4b is H, R 4c is OMe, R ' 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)CH cPr R R 44aa iis Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et)CH 2 cPr, R R 44aa iis Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Pr)CH2cPr R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Pr, R 4a iiεs Cl, R 4b is H, R 4c is OMe, R 4d is H and R e is H; a compound of Formula (50) wherein R 3 is N(Me)Et, R 4a is Cl, R 4b is H, R 4c is OMe, R d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Bu, R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N (Me) propargyl, R 4a i s cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et) propargyl, R 4a i s cl , R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(CH 3 )CH(CH 3 )CH 3 , R 4a is cl , R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH2CH 2 OMe) - CH 2 CH=CH 2 , R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is ■ 195- H and R 4e is H; a compound of Formula (50) wherein R 3 is N ( CH 2 CH 2 OMe ) Me, R a is C l, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N ( CH 2 CH 2 OMe ) Et, R 4a is C l , R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N ( CH 2 CH 2 OMe ) Pr, R 4a is cl , R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe) - CH 2 cPr, R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(CH 3 )CH 2 CH 3 , R 4a is Cl , R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(cPr) 2 , R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH OMe) 2 , R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(Et) 2 , R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et) 2 , R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(Et) 2 , R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; ■196- a compound of Formula (50) wherein R 3 is 2- ethylpiperid-1-yl, R 4a is cl , R is H/ R 4c ± i OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is cyclobutylaamminoo,, R R 44aa i i g s C l , R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N ( Me ) CH 2 CH=CH 2 , R 4a is Cl , R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N ( Et ) CH 2 CH=CH 2 , R 4 ig Cl , R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)CH 2 cPr R R 44aa iis Cl, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et)CH 2 cPr R R 44aa iis Cl, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N(Pr)CH 2 cPr, R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Pr, R 4a is cl, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Et, R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Bu, R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N (Me) propargyl, R 4a 1S cl, R b is H, R 4c is OMe, R 4d is F and R 4e is H; •197- a compound of Formula (50) wherein R 3 is NH ( CH ( CH 3 )CH(CH 3 )CH 3 , R 4 is C l , R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH 2 CH 2 OMe) - CH 2 CH=CH 2 , R a i s cl, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N ( CH 2 CH 2 OMe)Me, R a is Cl , R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Et, R a is C l , R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Pr, R a is cl , R 4b is H, R 4c is OMe, R d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH 2 CH 2 OMe) - CH cPr, R 4a i s cl, R 4b is H, R c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is NH(CH(CH 3 )CH 2 CH 3 , R 4a is Cl , R 4b is F, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(cPr)2, R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH2CH2θMe) 2 , R 4a is cl, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(Et) 2 , R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et) 2 , R 4a ■ 198- is Cl, R 4b is H, R 4c is OMe, R d is F and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(Et) R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is 2- ethylpiperid-1-yl, R 4a i s cl, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is cyclobutylamino, R 4a i s cl, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)CH 2 CH=CH 2 , R 4 is cl , R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et)CH 2 CH=CH 2 , R 4 i s cl, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)CH 2 cPr, R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et)CH cPr, R , 4 4 a a ii.s Cl, R 4b is H, R 4c is OMe, R 4d is OMe and R 4 ^ is H; a compound of Formula (50) wherein R 3 is N(Pr)CH cPr, Rc 44aa is Cl, R 4b is H, R 4c is OMe, R 4d is OMe and ,4e is H; a compound of Formula (50) wherein R 3 is N(Me)Pr, R 4a is Cl, R 4b is H, R 4c is OMe, R d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Et, R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is -199- H; a compound of Formula (50) wherein R 3 is N(Me)Bu R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N (Me ) propargyl, R 4a i s cl , R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is NH(CH(CH 3 )CH(CH 3 )CH 3 , R a is Cl , R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH 2 CH OMe) - CH 2 CH=CH 2 , R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Me, R 4a is cl , R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Et, R a is cl , R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Pr, R 4a i s cl , R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH2CH2θMe) CH 2 cPr, R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(CH 3 )CH 2 CH 3 , R 4a is Cl , R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(cPr) 2 , R 4a is cl, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; -200- a compound of Formula (50) wherein R 3 is N (CH 2 CH 2 0Me) 2 R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(Et)2, R 4a iiss Cl, R ' 4b is H, R 4c is OMe, R 4d is OMe and R ' 4e is H; a compound of Formula (50) wherein R 3 is N(Et) R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(Et)2, R 4a iiεs Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is 2- ethylpiperid-1-yl, R 4a i s Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is cyclobutylamino, R 4a is Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)CH 2 CH=CH 2 , R 4 is Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et)CH 2 CH=CH 2 , R 4a is Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)CH2cPr, R R 44aa iis Br, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et)CH2cPr, R 4a is Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; -201- a compound of Formula (50) wherein R 3 is N(Pr)CH2cPr R 4a is Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Pr R 4a liεs Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Et, R 4a is Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Bu R 4a is Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e i< H; a compound of Formula (50) wherein R 3 is N (Me) propargyl, R 4a i s B r, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is NH(CH(CH 3 )CH(CH 3 )CH 3 , R a is Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH 2 CH 2 OMe) - CH 2 CH=CH 2 , R 4a is Br, R 4b is H, R 4c is OMe, R 1£ F and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Me, R 4a is Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Et, R 4a is Br, R 4 is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Pr, R 4a 1S Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH 2 CH 2 OMe) - CH cPr, R 4a ig Br, R 4b is H, R 4c is OMe, R 4d is -202- OMe and R 4e is H; a compound of Formula (50) wherein R 3 is NH ( CH ( CH 3 ) CH 2 CH 3 , R 4a is B r, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(cPr) , R 4a is Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH 2 CH 2 OMe) 2 , R 4a is Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(Et) 2 , R 4a is Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et) 2 , R 4a is Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(Et) 2 , R 4a iiss Me, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is 2- ethylpiperid-1-yl, R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is cyclobutylamino, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)CH 2 CH=CH 2 , R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et)CH 2 CH=CH 2 , R 4a 1S Me, R 4b is H, R 4c is OMe, -203- R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)CH cPr R R 44aa iis Me, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N(Et)CH 2 cPr R 4a is Me, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Pr)CH 2 cPr R 4a is Me, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Pr R 4a iiss Me, R 4b is H, R 4c is OMe, R d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Et R 4a is Me, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(Me)Bu, R 4a iiss Me, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N (Me) propargyl, R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is NH(CH(CH 3 )CH(CH 3 )CH 3 , R 4a is Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH 2 CH OMe) - CH 2 CH=CH 2 , R 4a ig Me, R 4b is H, R 4c is OMe, R 4d is F and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Me, R 4a i s Me, R b is H, R 4c is OMe, R 4d is OMe and R 4e is H; -204- a compound of Formula (50) wherein R 3 is N(CH 2 CH 2 OMe)Et, R 4a is M e, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N ( CH 2 CH 2 OMe)Pr, R 4a is B r, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N(CH 2 CH2θMe) - CH 2 cPr, R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is NH(CH(CH 3 )CH 2 CH 3 , R 4a is M e, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(cPr) 2 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is N (CH 2 CH 2 OMe) 2 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (50) wherein R 3 is NHCH(Et) , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; and a compound of Formula (50) wherein R 3 is N(Et) 2 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H. A compound of Formula (60) -205- R 3 J N N" , CH. N V Ar FORMULA (60) and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt forms thereof, selected from the group: a compound of Formula (60) wherein R 3 is NHCH(Et)2, Ar is 6-dimethylamino-4 -methylpyrid-3 -yl; a compound of Formula (60) wherein R 3 is 2- ethylpiperid-1-yl, A r is 6-dimethylamino-4- methylpyrid-3-yl; a compound of Formula (60) wherein R 3 is cyclobutylamino, Ar is 6-dιmethylamino-4-methylpyrid-3 -yl ; a compound cf Formula (60) wherein R 3 is N(Me)CH CH=CH 2 , Ar is 6-dimethylamino-4- methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N(Et)CH 2 cPr, Ar is 6-dimethylamιno-4-methylpyrid-3-yl; a compound of Formula (60) wherein R 3 is N(Pr)CH 2 cPr, Ar is 6-dimethylamιno-4-methylpyrid-3-yl; -206- a compound of Formula (60) wherein R 3 is N(Me)Pr Ar is 6-dimethylamino-4-methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Me)Et Ar is 6-dimethylamino-4-methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Me)Bu Ar is 6-dimethylamino-4 -methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N ( Me ) propargyl, A r is 6-dimethylamino-4- methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Et) propargyl, A r is 6-dimethylamino-4- methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is NH(CH(CH 3 )CH(CH 3 )CH 3 , Ar is 6-dimethylamino-4- methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N (CH 2 CH 2 OMe) - CH2CH=CH 2 , Ar is 6 -dimethylamino-4 -methylpyrid-3 - yl; a compound of Formula (60) wherein R 3 is N(CH2CH 2 OMe)Me, Ar is 6-dimethylamino-4- methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(CH 2 CH 2 OMe)Et, Ar is 6 -dimethylamino-4- methylpyrid-3-yl ; -207- a compound of Formula (60) wherein R 3 is N ( CH 2 CH 2 OMe ) Pr, Ar is 6-dimethylamino-4- methylpyrid-3-yl ,- a compound of Formula (60) wherein R 3 is N(CH 2 CH 2 OMe) - CH 2 cPr, Ar is 6-dimethylamino-4 -methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is NH(CH(CH 3 )CH 2 CH 3 , A r is 6-dimethylamino-4- methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is NHCH(cPr) Ar is 6-dimethylamino-4 -methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N (CH 2 CH OMe) 2 , Ar is 6-dimethylamino-4-methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is NHCH(Et)2 Ar is 6-dimethylamino-4-methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Et) / Ar is 6-dimethylamino-4-methylpyrid-3-yl; a compound of Formula (60) wherein R 3 is 2- ethylpiperid-1-yl, r is 6-dimethylamino-4- methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is cyclobutylamino, Ar is 6-dimethylamino-4-methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Me)CH2CH=CH 2 , Ar is 6-dimethylamino-4- -208- methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N(Et)CH2cPr, Ar is 6-dimethylamino-4-methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Pr)CH2cPr Ar is 6-dimethylamino-4-methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Me)Pr, Ar is 6 -dimethylamino-4 -methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N(Me)Et, Ar is 6 -dimethylamino-4 -methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N(Me)Bu, Ar is 6-dimethylamino-4-methylpyrid-3-yl; a compound of Formula (60) wherein R 3 is N (Me) propargyl, Ar is 6-dimethylamino-4- methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is NH(CH(CH 3 )CH(CH 3 )CH 3 , A r is 6 -dimethylamino-4- methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(CH 2 CH 2 OMe) - CH 2 CH=CH2, Ar is 6 -dimethylamino-4-methylpyrid-3 - yl; a compound of Formula (60) wherein R 3 is N(CH2CH2θMe)Me, Ar is 6-dimethylamino-4- methylpyrid-3 -yl ; -209- a compound of Formula (60) wherein R 3 is N ( CH 2 CH2θMe ) Et, Ar is 6-dimethylamino-4- methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N ( CH2CH2θMe)Pr, Ar is 6 -dimethylamino-4 - methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N (CH 2 CH 2 0Me) - CH 2 cPr, Ar is 6-dimethylamino-4-methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is NH(CH(CH 3 )CH 2 CH 3 , Ar is 6-dimethylamino-4 - methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is NHCH(cPr) 2 , Ar is 6-dimethylamino-4-methylpyrid-3-yl; a compound of Formula (60) wherein R 3 is N (CH 2 CH 2 OMe) , Ar is 6-dimethylamino-4-methylpyrid-3-yl; a compound of Formula (60) wherein R 3 is NHCH(Et) , Ar is 6-dimethylamino-4 -methylpyrid-3 -yl; a compound of Formula (60) wherein R 3 is N(Et) 2 , Ar is 6-dimethylamino-4-methylpyrid-3-yl . a compound of Formula (60) wherein R 3 is 2- ethylpiperid-1-yl, Ar is 6- methoxy -4- methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is cyclobutyl - -210- am o, Ar is 6- methoxy -4 -methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N ( Me ) CH2CH=CH 2 , Ar is 6- methoxy -4-methylpyrid-3- yl; a compound of Formula (60) wherein R 3 is N(Et)CH 2 cPr Ar is 6- methoxy -4-methylpyrid-3-yl; a compound of Formula (60) wherein R 3 is N(Pr)CH2cPr, Ar is 6- methoxy -4-methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Me)Pr, Ar is 6- methoxy -4-methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Me)Et, Ar is 6- methoxy -4 -methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N(Me)Bu, Ar is 6- methoxy -4-methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N (Me) propargyl, Ar is 6- methoxy -4 -methylpyrid-3- yi; a compound of Formula (60) wherein R 3 is N(Et) propargyl, Ar is 6- methoxy -4-methylpyrid-3 - yl; a compound of Formula (60) wherein R 3 is NHCH(CH 3 )CH(CH 3 )CH 3 , A r is 6- methoxy -4- methylpyrid-3-yl ; -211- a compound of Formula (60) wherein R 3 is N (CH 2 CH 2 OMe) - CH 2 CH=CH2, Ar is 6- methoxy -4 -methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N ( CH2CH2θMe ) Me, Ar is 6- methoxy -4 -methylpyrid-3- yi ; a compound of Formula (60) wherein R 3 is N ( CH 2 CH 2 OMe ) Et, Ar is 6- methoxy -4 -methylpyrid-3- yl; a compound of Formula (60) wherein R 3 is N ( CH CH 2 OMe ) Pr, Ar is 6- methoxy -4 -methylpyrid-3- yi ; a compound of Formula (60) wherein R 3 is N (CH CH OMe) - CH 2 cPr, Ar is 6- methoxy -4 -methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is NHCH(CH 3 )CH2CH 3 , A r is 6- methoxy -4-methylpyrid- 3-yl; a compound of Formula (60) wherein R 3 is NHCH(cPr)2 Ar is 6- methoxy -4 -methylpyrid-3-yl ,- a compound of Formula (60) wherein R 3 is N (CH 2 CH 2 OMe) 2 , Ar is 6- methoxy -4 -methylpyrid-3 -yl ,- a compound of Formula (60) wherein R 3 is NHCH(Et)2 Ar is 6- methoxy -4 -methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Et) Ar is -212- 6- methoxy -4 -methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is 2- ethylpiperid-1-yl, Ar is 4-methoxy-6-methylpyrid- 3-yl; a compound of Formula (60) wherein R 3 is cyclobutylamino, Ar is 4 -methoxy- 6 -methylpyrid-3-yl; a compound of Formula (60) wherein R 3 is N ( Me ) CH 2 CH=CH 2 , A r is 4 -methoxy-6-methylpyrid-3 - yl; a compound of Formula (60) wherein R 3 is N(Et)CH 2 cPr Ar is 4 -methoxy- 6 -methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N(Pr)CH 2 cPr, Ar is 4 -methoxy-6-methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N(Me)Pr, Ar is 4 -methoxy- 6 -methylpyrid- 3 -yl ; a compound of Formula (60) wherein R 3 is N(Me)Et, Ar is 4 -methoxy-6-methylpyrid-3-yl; a compound of Formula (60) wherein R 3 is N(Me)Bu, Ar is 4 -methoxy-6 -methylpyrid-3-yl; a compound of Formula (60) wherein R 3 is N (Me) propargyl, Ar is 4 -methoxy-6 -methylpyrid-3- yi ; a compound of Formula (60) wherein R 3 is -213- NHCH(CH3)CH(CH 3 )CH 3 , A r is 4-methoxy-6- methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N (CH 2 CH 2 OMe) - CH CH=CH 2 , Ar is 4 -methoxy-6-methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N ( CH 2 CH 2 OMe ) Me, A r is 4 -methoxy-6 -methylpyrid-3- yi; a compound of Formula (60) wherein R 3 is N ( CH2CH2θMe ) Et, Ar is 4 -methoxy-6-methylpyrid-3 - yl; a compound of Formula (60) wherein R 3 is N ( CH 2 CH 2 OMe ) Pr, Ar is 4 -methoxy-6-methylpyrid-3- yi; a compound of Formula (60) wherein R 3 is N (CH 2 CH 2 OMe) - CH 2 cPr, Ar is 4 -methoxy- 6-methylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is NH(CH(CH3)CH 2 CH3, Ar is 4 -methoxy-6-methylpyrid-3 - yl; a compound of Formula (60) wherein R 3 is NHCH(cPr) , Ar is 4-methoxy-6-methylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N (CH CH 2 OMe) 2 , Ar is 4-methoxy- 6-methylpyrid-3-yl; a compound of Formula (60) wherein R 3 is NHCH(Et) 2 , Ar -214- is 6- methoxy -4 -methylpyrid-3-yl; a compound of Formula (60) wherein R 3 is N(Et) 2 , Ar is 4 -methoxy-6-methylpyrid-3-yl; a compound of Formula (60) wherein R 3 is 2- ethylpiperid-1-yl, Ar is 4 , 6-dimethylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is cyclobutyl - amino, Ar is 4 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N ( Me ) CH 2 CH=CH 2 , Ar is 4 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Et)CH2cPr, Ar is 4 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Pr)CH 2 cPr, Ar is 4 , 6-dimethylpyrid-3-yl; a compound of Formula (60) wherein R 3 is N(Me)Pr, Ar is 4 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Me)Et Ar is 4 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Me)Bu, Ar is 4 , 6-dimethylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N (Me) propargyl, Ar is 4 , 6-dimethylpyrid-3 -yl ; -215- a compound of Formula (60) wherein R 3 is N ( Et ) propargyl, A r is 4 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is NHCH(CH 3 )CH(CH 3 )CH 3 , A r is 4 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N (CH 2 CH 2 OMe) - CH 2 CH=CH 2 , Ar is 4 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(CH CH OMe)Me, Ar is 4 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(CH 2 CH 2 OMe)Et, Ar is 4 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(CH 2 CH 2 OMe)Pr, A r is 4 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N (CH2CH2θMe) - CH 2 cPr, Ar is 4 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is NHCH(CH 3 )CH 2 CH 3 , Ar is 4 , 6-dimethylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is NHCH(cPr) 2 , Ar is 4 , 6-dimethylpyrid-3-yl; a compound of Formula (60) wherein R 3 is N (CH 2 CH 2 OMe) 2 , Ar is 4, 6-dimethylpyrιd-3-yl; a compound of Formula ( 60 ) wherein R 3 is NHCH (Et ) 2 Ar is 4 , 6 -dimethylpyπd- 3 -yl ; -216 - a compound of Formula (60) wherein R 3 is N(Et) 2 Ar is 4 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is 2- ethylpiperid-1-yl, A r is 2 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is cyclobutylamino, Ar is 2, 6-dimethylpyrid-3-yl; a compound of Formula (60) wherein R 3 is N ( Me ) CH 2 CH=CH 2 , A r is 2 , 6-dimethylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N(Et)CH 2 cPr, Ar is Ar is 2 , 6-dimethylpyrid-3-yl; a compound of Formula (60) wherein R 3 is N(Pr)CH2cPr, Ar is Ar is 2 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Me)Pr, Ar is 2 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N(Me)Et, Ar is 2 , 6-dimethylpyrid-3 -yl ; a compound of Formula (60) wherein R 3 is N(Me)Bu, Ar is 2 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N (Me) propargyl, Ar is 2 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is -217- NH ( CH (CH 3 ) CH ( CH 3 ) CH 3 , A r is 2 , 6 -dimethylpyrid- 3 - yl ; a compound of Formula (60) wherein R 3 is N (CH CH OMe) - CH2CH=CH2, Ar is 2 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N ( CH 2 CH 2 OMe ) Me, Ar is 2 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N ( CH 2 CH 2 OMe ) Et, A r is 2 , 6-dimethylpyrid-3-yl ,- a compound of Formula (60) wherein R 3 is N ( CH 2 CH 2 OMe ) Pr, Ar is 2 , 6-dimethylpyrid-3-yl ; a compound of Formula (60) wherein R 3 is N (CH 2 CH 2 OMe) - CH2cPr, r is 2 , 6-dimethylpyrid-3-yl; a compound of Formula (60) wherein R 3 is NH(CH(CH 3 )CH 2 CH 3 , Ar is 2,6-dimethyl pyrid-3-yl; a compound of Formula (60) wherein R 3 is NHCH(cPr)2, Ar is 2,6-dimethyl pyrid- 3-yl; a compound of Formula (60) wherein R 3 is N (CH2CH2θMe) 2 , Ar is 2 , 6-dimethylpyrid-3-yl; a compound of Formula (60) wherein R 3 is NHCH(Et) 2 , r is 2 , 6 -dimethyl -pyrid- 3-yl; and a compound of Formula (60) wherein R 3 is N(Et) 2 , Ar is 2 , 6-dimethyl-pyrid-3 -yl . -218- 3. A compound and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt forms thereof, wherein said compound is selected from the group : 4- ( (2 -butyl) amino) -2, 7-dimethyl-8- (2 -methyl -4- methoxyphenyl) - [1, 5-a] -pyrazolo-1, 3, 5-triazine; 4- ( (2 -butyl) amino) -2 , 7-dimethyl-8- (2 , 5-di methyl -4- methoxyphenyl) - [1,5-a] -pyrazolo- 1, 3 , 5-triazine ; 4- ( (3-pentyl) amino) -2 , 7-dimethyl-8- (2, 5-dimethyl-4- methoxyphenyl) - [1,5-a] -pyrazolo- 1, 3 , 5 -triazine; 4- ( (3-pentyl) amino) -2, 7-dimethyl -8- (2 -methyl -4 - methoxyphenyl) - [1,5-a] -pyrazolo- 1, 3 , 5-triazine ; 4- (N-cyclopropylmethyl-N-propylamino) -2 , 7-dimethyl - 8- (2 -methyl -4 -methoxyphenyl) - [1, 5-a] -pyrazolo-1, 3 , 5- triazine; 4- (N-cyclopropylmethyl-N-propylamino) -2 , 7-dimethyl - 8- (2 , 5 -dimethyl -4 -methoxyphenyl) - [1, 5-a] -pyrazolo- 1,3, 5-triazine; 4- (N-allyl-N- (2-methoxyethyl) amino) -2 , 7-dimethyl-8- (2 -methyl -4 -methoxyphenyl) - [1,5-a] -pyrazolo- 1, 3,5- triazine; 4- ( N-allyl-N- (2-methoxyethyl) amino) -2, 7-dimethyl-8- (2 , 5 -dimethyl -4 -methoxyphenyl) - [1, 5-a] -pyrazolo- 1,3, 5-triazine; -219- 4- (diallylamino) -2 , 7-dimethyl-8- (2-met ' hyl-4- methoxyphenyl) - [1, 5-a] -pyrazolo-1, 3 , 5-triazine; 4- (diallylamino) -2 , 7-dimethyl-8- (2 , 5-dimethyl-4- methoxyphenyl) - [1, 5-a] -pyrazolo-1, 3 , 5-triazine,- 4- (N-ethyl-N- (2-methoxyethyl) amino) -2 , 7-dimethyl-8- (2 -methyl -4 -methoxyphenyl) - [1,5-a] -pyrazolo- 1, 3,5- triazine; and 4- ( N-ethyl-N- (2-methoxyethyl) amino) -2 , 7-dimethyl-8- (2 , 5 -dimethyl -4 -methoxyphenyl) -[1,5-a] -pyrazolo- 1,3, 5-triazine . 4. A compound of Formula (70) FORMULA (70) and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt forms thereof selected from the group : a compound of Formula (70) wherein R is Cl , R 3 is - NHCH (n-Pr ) 2 , R 4a is Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; -220- a compound of Formula (70) wherein R is Cl , R 3 is - NHCH ( CH 2 OMe ) 2 , R 4a is Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - N(CH 2 CH 2 OMe) 2 , R is M e, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is -N(c- Pr) (CH 2 CH 2 CN) , R 4a is M e, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - N ( CH 2 CH 2 OMe ) 2 , R 4a is Cl , R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl, R 3 is - NHCH ( CH 2 OMe ) 2 , R 4a is Cl , R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NHCH ( Et ) 2 , R 4a is Cl, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - N ( Et ) 2, R 4a is Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is -N(n- Pr) (CH 2 CH 2 CN) , R 4a i s Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is -N(n- Bu) (CH 2 CH 2 CN) , R 4a is Me, R 4b is H, R 4c is Me, R 4d i s H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NHCH(n-Pr) (CH 2 OMe) , R 4a i s Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl, R 3 is - NHCH(Et)2, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is -221- H and R 4 e is H ; a compound of Formula (70) wherein R is Cl, R 3 is - NHCH ( CH 2 OMe) 2 , R 4a is M e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is (S) NH ( CH 2 CH 2 OMe)CH 2 OMe, R 4a is M e, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; compound of Formula (70) wherein R is Cl, R 3 is - NH(CH 2 CH 2 OMe)CH 2 OMe, R 4 is Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - N ( CH 2 CH 2 OMe ) 2 , R 4a is Me, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NH ( Et ) , R 4a ig Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NHCH (n-Pr) 2 , R 4a is M e, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NHCH (CH 2 OMe) 2 , R 4a ia M e , R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl, R 3 is ( S) - NH(CH 2 CH 2 OMe)CH 2 OMe, R 4a is M e, R 4b is H, R 4c is Cl, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NH(CH 2 CH 2 OMe)CH 2 OMe, R 4a is Me, R 4b is H, R 4c is Cl, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is -N(n- Pr) (CH 2 CH 2 CN) , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; -222- a compound of Formula (70) wherein R is Cl , R 3 is - N ( Et ) 2 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is ( S) - NH(CH 2 CH 2 OMe)CH 2 OMe, R 4 is Cl , R 4b is H, R 4c is Me, JV ,4 * d" is H and R 4^e c is H; a compound of Formula (70) wherein R is Cl , R 3 is - NH(CH 2 CH 2 OMe)CH 2 OMe, R 4a is cl , R is H? R 4c ig Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - N ( Et ) 2 , R 4a is Cl, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is -N(c- Pr) (CH 2 CH 2 CN), R 4a is M e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is -N(c- Pr) (CH 2 CH 2 CN) , R 4a is cl , R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is -NHCH (n-Pr) (CH 2 OMe) , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is -NHCH (n-Pr) (CH 2 OMe), R 4a is Cl , R 4b is H, R 4c is Me, R d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NHCH ( Et ) 2 , R 4a is Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NHCH(Et) 2 , R 4a is Br, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - -223- N ( CH 2 CH 2 OMe) 2 , R 4a is Br, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NHCH ( CH 2 OMe) 2 , R 4a is Br, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - N ( Et ) 2 , R is Me, R 4b is H, R c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - N ( Et ) 2 , R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NHCH ( Et ) 2 , R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (70) wherein R is Cl, R 3 is - N(CH 2 CH 2 OMe) 2 , R 4a is Cl , R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NHCH (CH 2 OMe) 2 , R 4a is Cl , R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - N(Pr) (CH 2 CH 2 CN) , R 4a i s Cl , R 4b is H, R 4c is Cl , R 4d ig H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - N(Bu) (Et), R a is Cl, R 4b is H, R 4c is Cl , R 4d is H and R ' 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NHCH (Et)CH 2 OMe, R 4a i s Cl , R 4b is H, R 4c is Cl, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NHCH(Et) 2 , R 4a is Cl, R 4b is H, R 4c is Cl , R 4d is -224- H and R 4 e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NHCH ( Et) 2 , R 4a is Me, R 4b is H, R 4c is Me, R d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NHCH ( Et ) 2 , R 4 is Cl, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NHCH ( Et ) 2 , R 4a is Me, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NEt2, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; and a compound of Formula (70) wherein R is Cl, R 3 is - N(Pr) (CH 2 CH 2 CN) , R 4a is M e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NHCH (n-Pr) 2 , R 4a is Me, R 4b is H, R c is Me, R 4d is H and R e is H; a compound of Formula (70) wherein R is Me, R 3 is - NHCH (CH 2 OMe) 2 , R 4a i s Me, R b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - N(CH 2 CH 2 OMe) 2 , R 4a is M e, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is -N(c- Pr) (CH 2 CH 2 CN) , R a is Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - N(CH 2 CH 2 OMe) 2 , R a i s Cl , R 4b is H, R 4c is Me, R 4d is H and R 4e is H; -225- a compound of Formula (70) wherein R is Me, R 3 is - NHCH ( CH 2 OMe ) 2 , R 4a is C l, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NHCH ( Et ) 2 , R 4a is Cl, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - N ( Et ) 2 , R 4a is Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is -N(n- Pr ) ( CH 2 CH 2 CN ) , R 4a is Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is -N(n- Bu) (CH 2 CH 2 CN), R 4 is Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NHCH (n-Pr) (CH 2 0Me) , R 4a is M e, R 4b is H, R 4c it Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NHCH ( Et ) 2 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NHCH (CH 2 OMe) 2 , R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is ( S) NH(CH 2 CH 2 OMe)CH 2 OMe, R 4a i s M e, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NH(CH 2 CH 2 OMe)CH 2 OMe, R 4a i s Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is -226- N ( CH 2 CH 2 OMe) 2 , R 4 is M e, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NH ( Et ) , R 4a is Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NHCH ( n-Pr ) 2 , R 4a is Me, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NHCH ( CH 2 OMe ) 2 , R 4a is Me, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is ( S) NH(CH 2 CH 2 OMe)CH 2 OMe, R 4a is Me, R 4b is H, R 4c is Cl, R ' 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NH(CH 2 CH 2 OMe)CH 2 OMe, R 4a i s Me, R b is H, R 4c is Cl, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is -N(n- Pr) (CH 2 CH 2 CN) , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - N ( Et ) 2, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is ( S) ■ NH(CH 2 CH 2 OMe)CH 2 OMe, R 4a i s cl , R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NH(CH 2 CH OMe)CH 2 OMe, R 4a is Cl, R 4b is H, R 4c is Me, R d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - N ( Et) 2 , R 4a is Cl, R 4b is H, R 4c is Me, R 4d is H -227- and R 4 e is H; a compound of Formula (70) wherein R is Me, R 3 is -N(c- Pr ) ( CH 2 CH 2 CN) , R 4a is M e , R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is -N(c- Pr ) ( CH 2 CH 2 CN), R 4a is cl , R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is -NHCH (n-Pr) (CH 2 OMe), R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is -NHCH (n-Pr) (CH 2 OMe) , R 4a is cl , R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NHCH(Et) 2 , R 4a is Br, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NHCH(Et) 2 , R 4a is Br, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - N ( CH 2 CH 2 OMe ) 2 , R 4a is Br, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NHCH ( CH 2 OMe ) 2 , R 4a is Br, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - N(Et) 2 , R 4a is Me, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - N(Et) 2 , R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; -228- a compound of Formula (70) wherein R is Me, R 3 is - NHCH ( Et ) 2 , R 4 is Cl, R 4b is H, R 4c is OMe, R 4d i . OMe and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 i N ( CH 2 CH 2 OMe ) 2 , R 4a is Cl , R 4b is H, R 4c is Cl , R- is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NHCH ( CH 2 OMe) 2 , R 4a is Cl, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - N ( Pr) (CH 2 CH 2 CN), R 4a is cl , R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is N(Bu) (Et: ,4a is Cl, R 4b is H, R 4c is Cl, R 4 ind is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NHCH (Et)CH 2 OMe, R 4a is C l, R 4b is H, R 4c is Cl, R d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - . NHCH(Et) 2 , R is Cl, R 4b is H, R 4c is Cl , R 4d i £ H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NHCH(Et) 2 , R 4 is Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NHCH(Et) 2 , R 4a is Cl, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NHCH(Et) 2 , R a is Me, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is -229- NEt 2 , R 4a is Me, R 4b is H, R 4c is- OMe, R 4d is H and R 4e is H; and a compound of Formula (70) wherein R is Me, R 3 is - N ( Pr ) ( CH 2 CH 2 CN), R a i s Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH (n-Pr) 2 , R 4a is Me , R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH ( CH 2 OMe ) 2 , R a is Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N(CH 2 CH 2 OMe ) 2 , R 4 is Me, R b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is -N(c- Pr) (CH 2 CH 2 CN), R 4a is M e, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N ( CH 2 CH 2 OMe ) 2/ R 4a is Cl, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH ( CH 2 OMe ) 2 , R 4a is Cl , R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH(Et) 2 , R 4a is Cl, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N(Et) 2 , R 4a ig Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is -N(n- Pr) (CH 2 CH 2 CN) , R 4a is Me, R 4b is H, R 4c is Me, R d -230- is H and R4e is H; a compound of Formula (70) wherein R is F, R 3 is -N(n- Bu ) ( CH 2 CH 2 CN ) , R 4 is Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH(n-Pr) (CH 2 OMe) , R 4a is M e, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH ( Et ) 2 , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH(CH 2 OMe) 2 , R 4a is M e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is ( S) - NH(CH 2 CH 2 OMe)CH 2 OMe, R 4a is Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NH(CH 2 CH 2 OMe)CH 2 OMe, R 4 is M e, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N(CH 2 CH 2 OMe) 2 , R a is Me, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NH(Et), R 4a is Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH (n-Pr) 2 , R 4a is M e , R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH (CH 2 OMe) 2 , R 4a 1S M e, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; -231- a compound of Formula (70) wherein R is F, R 3 is ( S) - NH(CH 2 CH 2 OMe)CH 2 OMe, R a is M e, R 4b is H, R 4c is Cl, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NH(CH 2 CH 2 OMe)CH 2 OMe, R a is M e, R 4b is H, R 4c is Cl, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is -N(n- Pr) (CH 2 CH 2 CN), R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N ( Et) 2 , R 4a ig Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is ( S) - NH(CH 2 CH 2 OMe)CH 2 OMe, R 4a is C l , R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NH(CH 2 CH 2 OMe)CH 2 OMe, R 4a i s Cl , R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N(Et) 2 , R 4a i s cl, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is -N(c- Pr) (CH 2 CH 2 CN) , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is -N(c- Pr) (CH 2 CH 2 CN) , R 4a is cl , R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is -NHCH (n-Pr) (CH 2 0Me) , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is -NHCH -232- ( n-Pr ) ( CH 2 OMe), R a is cl , R 4b is H, R c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH ( Et ) 2 , R 4 is Br, R 4b is H, R c is OMe, R 4d i t OMe and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH ( Et ) 2 , R 4a is Br, R 4b is H, R 4c is OMe, R 4d i . H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N ( CH 2 CH 2 OMe ) 2 , R 4a is Br, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH ( CH 2 OMe) 2 , R a is Br, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N ( Et ) 2 , R 4a is Me, R 4b is H, R 4c is Cl, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N ( Et ) 2 , R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH ( Et ) 2 , R 4a is Cl, R 4b is H, R 4c is OMe, R 4d is OMe and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N ( CH 2 CH 2 OMe ) 2 , R 4a is Cl, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH ( CH 2 OMe ) 2 , R 4a is Cl, R 4b is H, R 4c is Cl, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N(Pr) (CH 2 CH 2 CN) , R 4a is cl, R 4b is H, R 4c is Cl , -233- R 4 d i s H and R 4 e is H ; a compound of Formula (70) wherein R is F, R 3 is - N ( Bu ) ( Et ) , R 4a is Cl, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH (Et)CH 2 OMe, R 4a is cl , R 4 is H/ R 4c ± s cl ^ R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH ( Et ) 2 , R 4a is Cl, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH ( Et ) 2 , R 4a is Me, R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH ( Et ) 2 , R 4a is Cl , R 4b is H, R 4c is Me, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NHCH ( Et ) 2 R 4a is Me, R 4b is H, R 4c is Cl , R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is -NEt2, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; and a compound of Formula (70) wherein R is F, R 3 is - N(Pr) (CH 2 CH 2 CN) , R 4 is M e, R b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl, R 3 is - N(Pr) (CH 2 CH 2 OMe) , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - N(Et) (CH 2 CH 2 OMe) , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; -234- a compound of Formula (70) wherein R is Cl, R 3 is - N ( Me ) ( CH 2 CH 2 OMe), R 4a is M e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NMeEt, R 4 is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NMePr, R 4 is M e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NMeBu, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl, R 3 is -NH- 2 -butyl, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is cyclobutylamino, R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - N(Pr) (CH 2 CH 2 OMe) , R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - N(Et) (CH 2 CH 2 OMe) , R 4a is M e, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - N(Me) (CH 2 CH 2 OMe) , R 4a i s Me, R 4b is H, R c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - N NMMeeEEtt,, RR 44aa iiεs Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; -235- a compound of Formula (70) wherein R is Cl , R 3 is - NMePr, R 4a is M e, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is - NMeBu, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is -NH- 2 -butyl, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is Cl , R 3 is cyclobutylamino, R 4a i s M e, R 4b is H, R 4c is OMe, R 4d is ME and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N(Pr) (CH 2 CH 2 OMe) , R a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N(Et) (CH 2 CH 2 OMe), R 4 is Me , R b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N(Me) (CH 2 CH 2 OMe) , R a is M e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NMeEt, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NMePr, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NMeBu, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is -NH-2- -236- butyl, R 4a ig Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is cyclobutylamino, R 4a i s M e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N(Pr) (CH 2 CH 2 OMe), R 4a is M e, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N(Et) (CH 2 CH 2 OMe), R a is Me , R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - N(Me) (CH 2 CH 2 OMe) , R 4 is M e, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NMeEt, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NMePr, R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is - NMeBu, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is -NH-2- butyl, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is F, R 3 is cyclobutylamino, R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - -237- N(Pr ) (CH 2 CH 2 OMe), R 4 is Me, R 4b is H, R 4c is OMe, ,4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - N ( Et ) (CH 2 CH 2 OMe), R 4a is M e , R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - N(Me) (CH 2 CH 2 OMe), R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NMeEt, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NMePr, R 4a is M e, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NMeBu, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is -NH- 2 -butyl, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is cyclobutylamino, R 4a i s Me, R b is H, R 4c is OMe, R 4d is H and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - N(Pr) (CH 2 CH 2 OMe) , R 4a ig M e, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - N(Et) (CH 2 CH 2 OMe), R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 i; -238- N ( Me ) ( CH 2 CH 2 OMe), R 4 is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NMeEt, R 4 i s Me , R 4 is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NMePr, R 4a is M e, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is - NMeBu, R 4 i s Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; a compound of Formula (70) wherein R is Me, R 3 is -NH- 2-butyl, R 4a is Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H; and a compound of Formula (70) wherein R is Me, R 3 is cyclobutylamino, R 4a i s Me, R 4b is H, R 4c is OMe, R 4d is Me and R 4e is H. 5. A compound and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt forms thereof, wherein said compound is selected from: 7- (diethylamino) -2 , 5-dimethyl-3- (2-methyl-4- methoxyphenyl- [1, 5-a] -pyrazolopyrimidine and 7- (N- (3-cyanopropyl) -N-propylamino) -2, 5-dimethyl-3- (2,4- dimethylphenyl) - [1, 5-a] -pyrazolopyrimidine. 6. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claims 1, 2, 3, 4 and 5. 7. A method of treating affective disorder, anxiety, -239- 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 claims 1, 2, 3, 4 and 5. -240-

Inventors: ARVANITIS ARGYRIOS GEORGIOS, CHORVAT ROBERT, GILLIGAN PAUL, HE LIQI, ARVANITIS, ARGYRIOS, GEORGIOS, CHORVAT, ROBERT, GILLIGAN, PAUL, HE, LIQI
Applicants: DU PONT PHARM CO, DU PONT PHARMACEUTICALS COMPANY
Application year: 1999
Main classification: C07D487
IPC codes: A61K31, A61P1, A61P3, A61P9, A61P15, A61P25, A61P29, A61P31, A61P37, A61P43, C07D487