MXPA99000990A

MXPA99000990A - Substituted triazolo-pyridazine derivatives as ligands for gaba receptors

Info

Publication number: MXPA99000990A
Application number: MXPA/A/1999/000990A
Authority: MX
Inventors: Barff Broughton Howard; Joseph Street Leslie; Robert Carling William; Luis Castro Pineiro Jose; Richard Guiblin Alexander; Madin Andrew; William Moore Kevin; Geoffrey Russell Michael
Original assignee: Barff Broughton Howard; Robert Carling William; Luis Castro Pineiro Jose; Richard Guiblin Alexander; Madin Andrew; Merck Sharp & Dohme Limited; William Moore Kevin; Geoffrey Russell Michael; Joseph Street Leslie
Priority date: 1996-07-25
Filing date: 1999-01-25
Publication date: 2000-02-02

Abstract

A class of substituted or 7,8-ring fused 1,2,4-triazolo[4,3-b]pyridazine derivatives, possessing an optionally substituted cycloalkyl, phenyl or heteroaryl substituent at the 3-position and a substituted alkoxy moiety at the 6-position, are selective ligands for GABA A receptors, in particular having high affinity for the&agr;2 and/or&agr;3 subunit thereof, and are accordingly of benefit in the treatment and/or prevention of disorders of the central nervous system, including anxiety and convulsions.

Description

TRIAZOLO-PIRIDAZINE DERIVATIVES REPLACED AS LEAGUE TWO OF GABA RECEIVERS The present invention relates to a class of substituted triazolo-pyridazine derivatives and their use in therapy. More particularly, this invention relates to substituted l, 2,4-triazolo [4,3-b] iridazine derivatives that are ligands of GABAA receptors and, therefore, are useful in the treatment of deleterious mental states. The most important inhibitory neurotransmitter receptors, gamma-aminobutyric acid (GABA), are divided into two main classes: (1) GABAA receptors that are members of a superfamily of ion channels opened by ligands and (2) receptors of GABAB, which may be members of the superfamily of G-protein-linked receptors. Since the first cDNA encoding individual GABAA receptor subunits was cloned, the number of known members of the mammalian family has increased to thirteen (six subunits a, three subunits ß, three subunits? a subunit-d). They may remain without discovering other subunits; however, since 1993 none has been described. Although knowledge of the diversity of the GABAA receptor gene family represents a major step towards our knowledge of this ligand-gated ion channel, an idea of the degree of diversity of subtypes is still in a premature state. It has been indicated that a subunit, a subunit ß and a subunit? they constitute the minimum requirements to form a fully functional GABAA receptor expressed by intermittent transfection of cDNA in cells. As indicated above, there is also a subunit d, although it is present only to a minimal degree in the GABAA receptor populations. Studies of receptor size and visualization by electron microscopy conclude that, like other members of the ion channel family opened by li- gandos, the native GABAA receptor exists in the form of a pentamer. The selection of at least one subunit a, one ß and one? of a repertoire of thirteen allows the possible existence of more than 10,000 combinations of pentameric subunits. Furthermore, this calculation does not take into account the permutations that would be possible if the arrangement of the subunits around the ion channel was not restricted (ie 120 variants would be possible for a receiver composed of five different subunits). Those with existing subtype receptor subtypes include, among many others alß2? 2. a2ß2 / 3? 2, 3?? 2/3, or? ß? l, 5? 3? 2/3, a? 2? 2, a? d and a4? d. Subtype sets containing a subunit are present in most areas of the brain and are thought to constitute 40% of the GABAA receptors in the rat. The sets of subunits containing a2 and a3, respectively, are believed to constitute approximately 25% and 17% of the GABAA receptors in the rat. The sets of subtypes that contain an a5 subunit are expressed primarily in the hippocampus and cortex and are thought to represent approximately 4% of the GABAA receptors in the rat. A characteristic property of known GABAA receptors is the presence of a series of modulation sites, one of which is the benzodiazepine binding site (BZ). The BZ binding site is the most explored of the GABAA receptor modulation sites and is the site through which anxiolytic drugs such as diazepam and temazepam exert their effect. Before cloning the gene family of the GABAA receptor, the benzodiazepine binding site was divided into two subtypes, BZ1 and BZ2, based on radioligand binding studies. Subtype BZ1 has been shown to be pharmacologically equivalent to a GABAA receptor comprising the subunit when combined with a β subunit and a β subunit. This is the most abundant subtype of GABAA receptor and, it is believed, representing almost half of all GABAA receptors in the brain. Two other important populations are the a2ß2 and a3ß2 2/3 subtypes. Together, these constitute approximately another 35% of the total repertoire of GABAA receptors.

Pharmacologically, this combination appears to be equivalent to subtype BZ2, as defined above by radioligand binding, although subtype BZ2 may also include certain subtype sets containing a5. The physiological function of these subtypes is so far unclear because selective agonists or antagonists are not sufficiently known. It is now believed that agents acting as BZ agonists in the alβ2, a2β2 or a3β2 subunits will possess desirable anxiolytic properties. The compounds that are modulators of the benzodiazepine binding site of the GABAA receptor that act as BZ agonists are referred to herein as "GABAA receptor agonists". GABAA receptor agonists selective for alpidam and zolpidam are clinically prescribed as hypnotic agents, suggesting that at least part of the sedative effect associated with anxiolytic drugs acting at the BZ1 binding site is mediated by GABAA receptors containing the subunit al. Therefore, it is considered that GABAA receptor agonists that bind more efficiently to subunit a2 and / or a3 than subunit al, will be effective in the treatment of anxiety, with a low tendency to cause sedation. . In addition, agents that are antagonists or inverse agonists in al could be used to reverse sedation or hypnosis caused by al agonists. The compounds of the present invention, being selective proteins of GABAA receptors, can therefore be used in the treatment and / or prevention of a series of disorders of the central nervous system. Such disorders include anxiety disorders, such as panic disorder with or without agoraphobia, agoraphobia without a history of panic disorder, animal phobias or other types of phobias including social phobias, obsessive-compulsive disorder, stress disorders including post-stress disorder. traumatic and acute, and generalized or substance-induced anxiety disorder; neurosis; convulsions; migraine; and depressive or bipolar disorders, for example, isolated or recurrent major depressive disorder, dysthymic disorder, bipolar I and bipolar II depressive disorders, and cyclotid disorder. monkey. In DE-A-2741763, and in U.S. Patents 4,260,755, 4,260,756, and 4,654,343, various classes of 1, 2,4-triazolo [4,3-b] derivatives are disclosed. pyridazine, which are described for their usefulness as anxiolytic agents. The de-aryl compounds in DE-A-2741763 and in U.S. Patents 4,260,755 and 4,654,343 have a phenyl substituent in the 6-position of the triazolo-pyridazine ring system. In contrast, the compounds described in U.S. Patent 4,260,756, possess a heteroaryl moiety in positions 6- and 8-. However, none of these publications describe or suggest 1, 2,4-triazolo [4,3-b] pyridazine derivatives in which the substituent at position 6 is linked by a directly bonded oxygen atom. EP-A-0085840 and EP-A-0134946 describe a series of related l, 2,4-triazolo [3,4-a] phthalazine derivatives which, it is claimed, possess anti-anxiety activity. However, there is no description or suggestion in any of these publications about the replacement of a benzo residue of the pyrazolo-phthalazine ring system with any other functional group. The present invention provides a class of triazolo-pyridazine derivatives possessing desirable binding properties to the GABAA receptor subtypes. The compounds according to the present invention possess good affinity as ligands for the a2 and / or a3 subunit of the human GABAA receptor. The compounds of this invention may present a more effective binding to the a2 and / or a3 subunit than to the a subunit. It is desirable that the compounds of the invention exhibit functional selectivity in terms of a selective efficacy for the a2 and / or a3 subunit with respect to the α subunit. The compounds of the present invention are HGAndos of the GABAA receptor subtype that have binding affinity (K1) for the a2 and / or a3 subunit, as measured in the assay described below, of 100 nM or less, typically 50 nM or less and ideally 10 nM or less. The compounds according to this invention can possess a selective affinity of at least two times, suitably at least 5 times and, advantageously at least 10 times, by the subunit a2 and / or a3 with respect to the subunit al. However, compounds that are not selective in terms of their binding affinity for the a2 and / or a3 subunit with respect to the subunit a are also included within the scope of the present invention; such compounds will desirably exhibit functional selectivity in terms of a selective efficiency for the a2 and / or a3 subunit with respect to the subunit a. The present invention provides a compound of formula I, or a salt or prodrug thereof: (I) wherein Y represents hydrogen or Ci-β alkyl; and Z represents C6-6 alkyl, C3-7 cycloalkyl, C7 cycloalkule, aryl, C3-7 heterocycloalkyl, heteroaryl or di (C6-6 alkyl) amino, any of said groups being optionally substituted; or Y and Z are taken together with the two intermediate carbon atoms to form a ring selected from C5-9 cycloalkenyl, C-io bicycloalkenyl, tetrahydropyridinyl, pyridinyl and phenyl, any of said rings optionally being benzo-condensed and / or substituted; R1 represents C3-7 cycloalkyl, phenyl, furyl, thienyl or pyridinyl, and can be any of said groups optionally substituted; and R2 represents cyanoalkyl (C6.6), hydroxyalkyl (C6-6), (C3-7 cycloalkyl) (C1-6 alkyl), propargyl, (Cs-7 heterocycle) alkylcarbonyl (Ci-β alkyl), aryl ( Ci-β alkyl) or heteroaryl (Ci-β alkyl), any of said groups optionally substituted; . provided that, when Y and Z are taken together with the two intermediate carbon atoms to form an optionally substituted phenyl ring, then R2 is not hydroxy (Ci-e alkyl). In addition, the present invention provides a compound of formula I, as defined above, or a salt or prodrug thereof, wherein Y represents hydrogen or Ci-β alkyl; and Z represents Ci-β alkyl, C3-7 cycloalkyl, aryl, (C3-7 heterocycle) alkyl or heteroaryl, any of said groups optionally substituted; or Y and Z are taken together with the intermediate carbon atoms to form a ring selected from C5-9 cycloalkenyl, C6-biocycloalkenyl, tetrahydropyridinyl, pyridinyl and phenyl, wherein any of said rings optionally benzocondensate and / or substituted and R1 and R2 may be they are as defined above; provided that, when Y and Z are taken together with the two intermediate carbon atoms to form an optionally substituted phenyl ring, then R2 is not hydroxy (Ci-β alkyl). The present invention further provides a compound of formula I as defined above, or a salt or prodrug thereof, wherein Y represents hydrogen or Ci-β alkyl; and Z represents Ci-e alkyl, C3.7 cycloalkyl, aryl, (Cw alkyl or heteroaryl heterocycle, any of which may be optionally substituted, or Y and Z are taken together with the two intermediate carbon atoms forming a ring selected from C5-9 cycloalkenyl, C-io bicycloalkenyl, tetrahydropyridinyl, pyridinyl and phenyl, any of which may be optionally benzocondensate and / or substituted; R1 is as defined above; and R2 represents hydroxy (Ci-β alkyl), (C3-7 cycloalkyl) (Ci-β alkyl), (heterocycle) C -. 7) alkylcarbonyl (Ci-β alkyl), aryl (Ci-β alkyl) or heteroaryl (Ci-β alkyl), any of which may be optionally substituted; provided that, when Y and Z are taken together with the two intermediate carbon atoms to form an optionally substituted phenyl ring, then R2 is not hydroxy (Ci-β alkyl). The present invention further provides a compound of formula I, as defined above, or a salt or prodrug thereof, wherein Y represents hydrogen or Ci-β alkyl; and Z represents Ci-β alkyl, C3-7 cycloalkyl, aryl, (C3-7 heterocycle) alkyl or heteroaryl, any of which may be optionally substituted; or Y and Z are taken together with the two intermediate carbon atoms to form a ring selected from C5-9 cycloalkenyl, C-io bicycloalkenyl, tetrahydropyridinyl and pyridinyl, any of which may be benzocondensate and / or substituted; R1 is as defined above; and R2 represents hydroxy (Ci-β alkyl), (C3-7 cycloalkyl) (Ci-β alkyl), (heterocycle) C3-7) alkylcarbonyl (Ci-β alkyl), aryl (Ci-β alkyl) or heteroaryl (C?-6 alkyl), any of which may be optionally substituted. When Y and Z are taken together with the two carbon atoms to form a ring, the resulting compounds of formula I above incorporate the cycloalkenyl, bicycloalkenyl, tetrahydropyridinyl, pyridinyl or phenyl ring fused with the triazolo-pyridazine ring system as depicted in formula I.

When Y and Z are taken together with the two carbon atoms to form a C5-9 cycloalkenyl ring. this ring may optionally be a cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl or cyclononenyl ring, suitably cyclohexenyl or cycloheptenyl. When Y and Z are taken together with the two intermediate carbon atoms to form a bicycloalkenyl C C-io ring, this ring can be a bicyclo [2.1.1] hex-2-enyl, bicyclo [2.2.1] hept-2- ring. enyl, bicyclo [2.2.2] oct-2-enyl, bicyclo [3.2.2] non-6-enyl or bici-clo [3.3.2] dec-9-enyl, suitably bicyclo [2.2.1] hept -2-enyl, bicyclo [2.2.2] oct-2-enyl or bicyclo [3.2.2] non-6-enyl, and especially bicyclo [2.2.2] oct-2-enyl. When Y and Z are taken together with the two carbon atoms to form a ring, this ring may be optionally benzo-condensed. By way of illustration, Y and Z taken together with the two intermediate carbon atoms can represent a benzocondensed cyclohexenyl ring, whereby the resulting ring is dihydronaphthyl. The groups Y, Z, R1 and R2 may be unsubstituted, or substituted by one or two substituents. In general, groups Y, Z, R1 and R2 will be unsubstituted or monosubstituted. Examples of optional substituents of the groups Y, Z, R1 and R2 include d-β alkyl, aryl (Ci-β alkyl), pyridyl (Ci-β alkyl), halogen, halo (Ci-β alkyl), cyano, cyano ( Ci-β alkyl), hydroxy, hydroxymethyl, Ci-β alkoxy, (C 3-7 cycloalkyl) (O-β alkoxy), C 3-7 cycloalkoxy, amino (Ci-β alkyl), di (C 1 -C 6 alkyl) amino (C C-b) alkyl, di (C?-alkyl) 6-aminocarbonyl (Ci-β alkyl), α- (alkyl-6) piperidinyl, pyrrolidinyl (Ci-β alkyl), piperazinyl (Ci-β alkyl) , morpholinyl (Ci-β alkyl), di (C 1 -C 6 alkyl) morpholinyl (Ci-β alkyl) and imidazolyl (Ci-β alkyl). Exemplary substituents include C 1-6 alkyl, aryl (Ci-e alkyl), pyridyl (Ci-β alkyl), halogen, halo (Ct-β alkyl), cyano, cyano (Ct-β alkyl), hydroxy, hydroxymethyl, Ci-β alkoxy, (C3-7 cycloalkyl) (Ci-e alkoxy), di (Ci-6 alkyl) amino (Ci-β alkyl), di (C C-6 alkyl) aminocarbonyl (Ci-o alkyl), morpholinyl (Ci-β alkyl) and imi-dazolyl (alk or Ci-β). Representative substituents include Ci-β alkyl, aryl (Ci-β alkyl), halogen, cyano, hydroxy, hydroxymethyl, C 1-6 alkoxy and (C 3-7 cycloalkyl) (Ci-β alkoxy).

As used herein, the term "C.alkyl," includes methyl and ethyl groups and straight and branched chain propyl, butyl, pentyl and hexyl groups Particular alkyl groups are methyl, ethyl, "-propyl, isopropyl, / ere-butyl and 1,1-dimethylpropyl Accordingly, expressions derived as "CiV alkoxy" will be interpreted in a similar manner C3-7 cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. C3-7 cycloalkyl) (C alquilo .¿ alkyl) "as used herein includes cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl and cyclohexylmethyl Typical C 4-7 cycloalkenyl groups include cyclobutenyl, cyclopentenyl and cyclohexenyl Typical aryl groups include phenyl and naphthyl, preferably phenyl The term "aryl (Ci-β alkyl)" as used herein includes benzyl, phenylethyl, phenylpropyl and naphthylmethyl Suitable heterocycloalkyl groups include azetidinyl, pyrrolyl groups dinyl, piperidinyl, piperazinyl, morpholinyl and thiomorpholinyl. Suitable heteroaryl groups include pyridinyl, quinolinyl, isoquinolinyl, pyridazinyl, pyrimidinyl, pyrazinyl, quinoxalinyl, furui, benzofuran, dibenzofuran, tienflo, benzothien, pyrrole, indole, pyrazolyl, indazole, oxazole, isoxazole, thiazolyl, isothiazole, imidazole, benzimidazole, oxadiazolyl, thiadiazolyl, triazole and tetrazolyl. The term "heteroaryl (Ci-β alky)" as used herein includes furylmethyl, furylethyl, thienylmethyl, thienylethyl, pyrazolylmethyl, oxazolemethyl, oxazolyl, iso-xazolylmethyl, thiazolylmethyl, thiazolethyl, imidazolylmethyl or imidazolylethyl. , benzimidazolylmethyl, oxadiazolylmethyl, oxadiazole etho, thiadiazolylmethyl, thiadiazolyl, trifiazolylmethyl, triazolyl, tetrazolylmethyl, tetrazolyl, pMdinylmethyl, pminidylethyl, pyridazinylmethyl, pyridinomethyl, pyridinyl, quinolinylmethyl, isoquinolinylmethyl and quinoxalinylmethyl.

The term "halogen" as used herein includes fluorine, chlorine, bromine and iodine, especially fluorine or chlorine. For use in medicine, the salts of the compounds of formula I will be pharmaceutically acceptable salts. However, other salts may be used in the preparation of the compounds of the invention or their pharmaceutically acceptable salts. Suitable pharmaceutically acceptable salts of the compounds of this invention include the acid addition salts which, for example, can be formed by mixing a solution of the compound according to the invention with a solution of a pharmaceutically acceptable acid such as hydrochloric acid, sulfuric acid, methanesulfonic acid, fumaric acid, maleic acid, succinic acid, acetic acid, benzoic acid, oxalic acid, citric acid, tartaric acid, carbonic acid or phosphoric acid. In addition, when the compounds of the invention have an acidic moiety, the pharmaceutically acceptable salts include alkali metal salts, for example, sodium or potassium salts; alkaline earth metal salts, for example calcium and magnesium salts; and salts formed with suitable organic compounds, for example, quaternary ammonium salts. The present invention includes within its scope the prodrugs of the compounds of formula I above. In general, such prodrugs will be functional derivatives of the compounds of formula I which are readily converted in vivo to the desired compound of formula I. Conventional procedures for the selection and preparation of suitable prodrug derivatives are described, for example, in Design of Prodrugs , ed. H. Bundgaard, Elsevier, 1985. When the compounds according to the invention have at least one asymmetric center, they can therefore exist in the form of enantiomers. When the compounds according to the invention have two or more asymmetric centers, they can also exist in the form of diastereomers. It is understood that such isomers as well as their mixtures in any proportion are included within the scope of the present invention.

Suitably, Y represents hydrogen or methyl, and especially hydrogen. Examples of suitable values for the substituent Z include methyl, ethyl, isopropyl, tere-butyl, 1,1-dimethyl-royl, methyl-cyclopropyl, cyclobutyl, methyl-cyclobutyl, cyclopentyl, methyl-cyclopentyl, cyclohexene, cyclobutenyl, phenyl, pyrrohdin , met-ñ-pyrrohydrole, piperidinyl, morpholinyl, thiomorpholyrin, pyridinyl, furyl, thienyl, chloro-tertiary and diethylamino. Fluctive values of Z include methyl, ethyl, isopropflo, / ere-butyl, methyl-cyclopropane, cyclobutyl, methyl-cyclobutyl, cyclopentyl, methyl-cyclopentyl, cyclohexine, pheno, pyrroHdin or, methyl-pyrrohdin, piperidin, morpholin, thiomorpholine, pyridimide. , furilo, tienño and chloro-tierulo. Typical values include meth, ethno, pheno, piperidin, pyridinium and thieno. In a particular embodiment, the substituent Z represents C3-7 cycloalkane, whether unsubstituted or substituted by C1-6 alkane, especially methyl. Ideally, Z represents cyclobutne. When Z and Y are taken together with the intermediate carbon atoms to form a ring, representative compounds according to the invention include those of structure IA to ILO, especially IA to IK: (ID) (IE) (IF) (IG) (IH) wherein R1 and R2 are as defined above; R 3 represents hydrogen, C 1 -6 alkane, arne (C 1 alkoxy), halogen, cyano, hydroxy, hydroxymethyl or Ci-β alkoxy; and R 4 represents hydrogen or Ci-β alk. Suitably, R3 represents hydrogen or C alqu-6 alk, especially hydrogen or meth. Suitably, R 4 represents hydrogen or meth. Preferred triazolo-pyridazine derivatives according to the present invention include the compounds represented by formula IE represented above. Examples of substituents typical of the R1 group include meth, fluoro and methoxy. Representative values of R1 include cycloprophene, phenol, metfenfen, fluoro-phenol, difluorophenone, methoxyphenone, furui, thieno, methylene and pyridinium. Particular values include ciclopropño, fenño, metüfenüo, fluorofenño, metoxifenño and piridinño. More espe- Finally, R1 can represent an unsubstituted or monosubstituted phenotype. Most preferred, R1 represents phenol. Suitable values of the substituent R.sup.2 in the compounds according to the invention include cyanomethyl, hydroxybutyl, cyclohexylmethyl, propargin, pyrrolidinibcarbo-nylmethyl, benzin, pyrazolylmethyl, isoxazolemethyl, thiazolemethyl, thiazolethyl, imidazolemethyl, benzimidazolemethyl, oxadiazolemethyl, triazolylmethyl, tetrazolemethyl, pyridinimethane, -darzinimethane, pyrimidinimeti, pyrazinimetin, quinolinimetin, isoquinolinimetim and qui-noxalinimetim, any of which may be optionally substituted by one or more substituents. Typical values of R 2 include hydroxybutyl, cyclohexammethyl, pyrrohydrocarbonate, benzyl, pyrazolemethyl, thiazolimethane, imidazolemethyl, triazolylmethyl, pyridiniummethyl, pyridazinimethane, pyrimidinimethane, pyrazinimetin, quinolinümene, isoquinolinumimethane and quinoxalinimethane, any of which may be optionally substituted by one or more substituents Examples of suitable optional substituents of the R 2 group include C 1 -6 alkyl, aryl (Ci-β alky), pyridine (Ci-0 alkyl), halogen, halo (Ci-o alk), cyano, cyano (Ci-e alky) , hydroxymethyl, C6-6 alkoxy, (C7.7 cycloalkyl) (C6-6 alkoxy), amino (Q-ß alky), di (Ci-d alky) -amino (β-alkyne), di (Alkyl C) ? -6) aminocarbonü (alkyl Ci.β), jV- (alkyl C? -6) pi? Eridin? N, pi-rrohdin? (Alk? -ó), pi? Erazin? (Alkyl Ci?), Morpholinin (alk-Ci? ) and di (alk Q-6) morpholin (Al Ot-ß). Exemplary substituents include Ci-β alky, arü (Ci-β alky), pi-rhyme (Ci-β alky), halogen, halo (Ci-β alky), cyano, cyano (Ci-β alky), hydroxymethyl, alkoxy C? -6, (C3-7 cycloalkyl) (Ci-o alkoxy), di (C? -6) alkylamino (Ci-ß alky), di (Ci- 6 alky) aminocarbon (Ci-ß alky) and morpholine (Allo Ci-ß). Typical substituents include alche C? -6, arñ (Ci-ß alkyl), halogen, cyano, hydroxymethyl, Ci-e alkoxy and (C3-7 cycloalkyl) (Ci-β alkoxy). Specific illustrations of particular substituents in the group R 2 include methyl, ethyl, n-prophenol, benzyl, pyridinimethane, chloro, chloromethyl, cyano, cyanomethyl, hydroxyethyl, ethoxy, cyclopropermethoxy, dimethyaminomethyl, aminoethyl, dimethylamine, dimethylamine. lamino-carbonñmetüo, iV-metüpiperidinño, pirrohdinñetño, piperazinñetüo, morfolinñmetüo and din etñrnorfolinilmetüo. More specific illustrations of particular substituents in the R 2 group include methylene, etho, "-propno, benzno, phenemetim, chloro, chlorometiuo, cyano, cyanomethyl, hydroxymethyl, ethoxy, cyclopropylmethoxy, dimethyaminometiu, dimethyaminoethyl, dimethylamino-carbonylmethin and morpholinimethane. Representative values of R2 include cyanomethyl, hydroxybutyl, hydroxymethyl-cyclohexylmethyl, propargin, dimethylaminomethyl-propargue, diinethyl-rnorfolinyl-methane-propargue, pyrroxycarbonnemethane, cyanobenzyl, hydroxymethylbenzene, pyrazolylmethyl, di-methy-pyrazoluene, metho-isoxazolemethyl, thiazolemethyl, metho-thiazolylmethyl , ethyl-thiazolylmethyl, methyl-thiazole, imidazole, methyl-imidazole, ethane-imidazole, benzene-imidazolylmethyl, benzimidazole, methane-oxadiazole, triazole, methanetriazole, propium triazole, benzoletriazolide, pyridinemethoxazole, cyanidene -triazoliknetño, dimetñammometü-triazolümetilo, aminoethyl triazolñmetño, dimetñaminoetü-triazolilmetño, dimetüam ocarbonñmetñ-triazolilmetüo, N-rnetüpiperidinü-triazolilmetüo, pirrohdinüetü-triazolñmetño, piperazinñetü-triazolñmetüo, morfolinüetñ-triazolñmetño, metU-tetrazolilmetüo, pMdinilmetño, Metn-pyridin METNO, di e-tN-piridinümetño, ethoxy-piridiniknetilo, ciclopropñmetoxi-piridinümetüo, piridazinilmetño, chloro-piridazinilmetño, pirimidinümetño, pirazinümetño, quinolinñmetüo, isoquinolinümetño and quinoxalinñmetüo. Exemplary values of R2 include cyanomethyl, hydroxybutyl, hydroxymethyl-cyclohexamethyl, propargum, dimethyaminomethane-propargno, pyrroxycarbonylmethoxy, cyanobenzyl, hydroxymethyl-benzyl, pyrazolylmethyl, dimethyl-pyrazolylmethyl, methy-isoxazolylmethyl, thiazolemethyl, metha-thiazolethyl, ethano-thiazolemethyl, methanediazole. , imidazolemethyl, methyl-imidazolylmethyl, ethyl-imidazolylmethyl, benzyl-imidazolylmethyl, benzimidazolemethyl, methyl-oxadiazolemethyl, triazolylmethyl, methy-triazolemethylene, propr-azolethylene, benzene, triazolylmethyl, pMdinñrnetü-triazolilrnetño, cyanomethyl-triazolylmethyl, cümetílaminometil-triazolylmethyl, dimetñaminoetü-triazolñmetño, dimetñaminocarbonümetü-triazolilmetüo, morfolinüetü-triazolümetüo, metU-tetrazolñmetño, pyridinylmethyl, Metn-piridinñmetüo, dime-til-piridinñrnetilo, ethoxy-piridinümetüo, cidopropilmetoxí-pMdinümetño, pMdazinilmetüo, chloro-pyridazinimmethyl, pyrimidinimethane, pyrazinimeti, quinolinümene, isoquinolinümene and quinoxal urnnetilo. Particular values of R2 include hidroxibutüo, hidroximetü-ciclohexümetño, pirroHdinücarboniknetño, cianobencüo, hidroximetñ-bencüo, pirazolñmetño, dimetü-pirazolümetüo, tiazolümetño, Metn-tiazolilmetüo, ETU-thiazolylmethyl imidazolñmetüo, Metn-imidazolñmetño, ETN-imidazolñmetüo, bencü-imidazolümetüo, Metn -triazolümetüo, pi-ridinñmetüo, metñ-piridinñmetño, ditaetü-piridinümetño, ethoxy-pyridinüm, cidopropñ-inetoxi-piridinilmetño, piridazinñmetüo, doro-p dazinilmetilo, pirimidiriñmetüo, pirazinñ-methyl, quinolinñmetño, isoquinolinilmetüo and quinoxalinñinetüo. A preferred value of R2 is methan-triazolium. A particular subgroup of compounds according to the invention is represented by the compounds of formula HA, and the salts and prodrug thereof: wherein R1 is as defined above; n is 1, 2, 3 or 4, typically 1; Y R 12 represents hydroxy; or C3-7 cydoalkyne, (C3-7 heterodoxy) alkanocarbon, aryl or heteroaryl, any of which may be optionally substituted. Examples of optional substituents in the R12 group suitably include C1-6 alkyl, arn (Ci-o alk), halogen, cyano, hydroxymethyl, C6-6 alkoxy and (C3-7 cycloalkyl) (C1-6 alkoxy). . Typical substituents include methi, ethno, benzno, doro, cyano, hydroxymethyl, ethoxy and cidopropumethoxy. Particular values of R12 include hydroxy, hydroxymethyl-cidohexyl, pyrrolidinecarbon, cyanophenium, hydroxymethyl-phenoyl, pyrazolide, dimethyrazoluene, thiazolium, methytia-zolium, ethylthiazole, imidazole, methylimidazolyl, etimimidazolium, benzimidazole, metutria-zolin, pyridinium, methypyridinium, dimethy pyridyl, ethoxypyridinium, cidopropylmethoxy pyridinium, pyridazinium, doropyridazinium, pyrimidinium, pyrazinium, quinolinium, isoquinolinium and quinoxalinium. Another subgroup of compounds according to the invention is represented by the compounds of formula IIB, and the salts and prodrugs thereof: (IIB) wherein Y1 represents hydrogen or meth; Z1 represents C alqu-6 alkyl, C 3-7 cycloalkane, C 4-7 cydoalkeno, arino, C 3-7 heteroalkanoalkyl, heteroaryl or di (C?-6) alkylamino, any of which may be optional. nally replaced; R1 is as defined with reference to formula I above; m is 1 or 2, preferably 1; and R22 represents aryl or heteroaryl, any of which may be opponally substituted. The present invention also provides a compound of formula IIB, as defined above, or a salt or prodrug thereof, wherein Z1 represents C? -6 alky, C3-7 cyanoalkano, arno, C3-7 heterocyclic alkaloid or heteroaryano? , any of which may be optionally substituted; and Y1, R1, m and R22 are as defined above. Suitably Y1 represents hydrogen. Examples of typical substituents in the group Z1 include C1-6 alkyl and halogen, especially methyl or doro. Values representative of the Z1 group include methyl, ethyl, isopropyl, tert-butyl, 1,1-dimethypropyl, methidopid, cidobuthane, methyndebutyl, dpentone, methylddopentone, cidohexene, cidobutene, phenole, pyrrolidinone, met-pyrrolidinone, piperidinium, morpholinium, thiomorpholinium, pyridinium, furyl, thieno, chloro-thieno and diethylamine. Particular values for the Z1 group include methyl, ethoxy, isopropene, tere-butyl, metido-cidopropine, cidobuthane, methy-cidobutyl, cidopentyl, meth-cidopentine, dhohe-xii, phenoxy, pyrroHdinium, methy-pyrroHydin, piperidin, morpholin, thiomorpholinium , pyridinyl, furyl, thieno and doro-thieno. A preferred value of Z1 is doubled. Examples of typical substituents in the R22 group include C1-6 alk, arn (Ci-ß alk), pyridu (Ci-io alkyl), halogen, cyano, cyano (Ci-ß alky), hydroxymethyl, C1-6 alkoxy, ( ddoalk3 C3-7) (Ci-ß alkoxy), di (C--6 alky) -amino (C 1-6 alky), amino (alky Oe), di (C--6 alky) aminocarbon ian (Ci alky) , -V- (Allo C? ^) Pi? Eridinüo, pirrohdinü (Allo Ci- ß), pi? erazinü (ali Ci-ß) and morfolinü (alño C.¿). Representative substituents include C alqu -6 alkyl, arñ (Ci-ß alk), pyridu (Ci-ß alk), halogen, cyano, cyano (Ct-d alk), hydroxymethyl, C?-6 alkoxy, (C3-7 cycloalkyl) ) (Ci-β alkoxy), di (C--6 alky) amino (Ci-ß alk), di (C--6) aminocarbon (Ci-alqu alk) and morpholin (C.. Exemplary values of specific substituents in the R22 group include meth, ethy, w-propy, benzene, pyridinimethane, doro, cyano, cyanomethyl, hydroxymethyl, ethoxy, cyprodoxymethoxy, dimethylaminomethyl, aminoethyl, dimethyaminoethyl, dimethylaminocarbonylmethyl, ? i? eridin?, pyrroHdin? et?, piperazin? et, and morpholinilmeth. Representative values of substituents in the group R22 include methyl, ethyl, propion, benzyl, pyridinylmethyl, doro, cyano, cyanomethyl, hydroxymethyl, ethoxy, cidopropyl-methoxy, dimethyaminomethyl, dimethyaminoethane, dimethylaminocarbonetim and morpholinimide. Particular values of R22 include cyanophenone, hydroxymethylene, pyrazole, dimethyne-pyrazolone, methane-isoxazole, thiazolium, methiu-thiazole, ethyl-thiazole, imidazole, me-t-imidazolium, ethylene imidazolium, benzyl imidazole, benzimidazolium. , metha-oxadiazole, triazo-Hlo, methyl-triazole, propr-triazole, benzin-triazole, pyridinemethane-triazole, cyanomethyl-triazole, dimetaminase-triazole, aminoethane-triazole, dimethylamineeti-triazolium, dimethyl-tertiary-carbon-triazole, IV-methylpiperidine -triazoHIo, pyrroHdinñetñ-triazolño, pipera-zinñetü-triazolño, morfoHnñetñ-triazoHlo, metü-tetrazolín, piridinño, metü-piridinño, dimetil-piridinüo, ethoxy-piridinño, ddopropümetoxi-piridinüo, pyridazinüo, doro-piridazinño, pirimidinño, pirazinño, quinolinño , isoquinolinium and quinoxalinin. Specific values of R22 include cyanofemlo, hydroxymethylene, pyrazolone, dimethyrazoluene, methiuoxazole, thiazole, metha-thiazole, etha-thiazole, imidazolium, methyl imidazole, etheimidazole, benzyl imidazolium, benzimidazole, methyl oxadiazole. , triazole, methyl-triazo-halo, prop-triazole, benzin-triazole, pMdirulmet-triazolium, cyanomethyl-triazolium, dimethyaminomethane-triazole, dimethylamine-triazole, dimethylaminecarbonate, triazole, morpholinethane-triazole, methan-tetrazole, pyridinium, methy-pyridinium, dimethy-pyridinone, ethoxy-pyridinone, cidopropiummethoxy-pyridinium, pyridazinium, doro-pyridazinium, pyrimidinium, pyrazin, quinolinium, isoquinolinium and quinoxalin. A preferred value of R22 is methi-triazolium. A particular subgroup of the compounds of formula IIB above is represented by the compounds of formula IIC and pharmaceutically acceptable salts thereof: (IIC) wherein R1 is as defined with respect to formula I above; Q represents the remainder of a ring of cyclopropyl, cidobutyl, cyclopentone or cyclohexyl; R5 represents hydrogen or methno; and R6 represents hydrogen or meth. With respect to the above IIC formula, R1 suitably represents phene. In a preferred embodiment, Q advantageously represents the remainder of a doudobutyl ring.

Suitably, R 5 represents hydrogen. Properly, R6 represents methyo. Specific compounds within the scope of the present invention include: 3-phene-6 ^ (2-pyridine) methoxy-7,8,9,10-tet-rahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 3,7-diphen-6- (2-pyridu) methyloxy-l, 2,4-triazolo [4,3-b] pyridazine; 3-Phen-6- (2-pMdn) methyloxy-7,8,9,10-tetrahydro-l, 2,4-triazolo [3,4-a] phthalazine; 7,8-di? Netyl-3-phen-6- (2-? Irid?) Rnethoxy-l, 2,4-triazolo [4,3-b] pyridazine; 7-methyl-3-phenyl-6- (2-pyridu) methyloxy-l, 2,4-triazolo [4,3-b]? Iridazine; 7-eti-3-phenyl-6- (2-? Iridu) methyloxy-l, 2,4-triazolo [4,3-b] pyridazine; 7,8-benzo-3-phenyl-6- (2-pyridu) methyloxy-7,8,9,10-tetrahydro-l, 2,4-triazolo [3,4-a] phthalazine; 8-n etü-3,7-dü: enñ-6- (2-? Iridü) methyloxy-l, 2,4-triazolo [4,3-b] pyridazine; 3-phenyl-6- (2-pyridine) methyloxy-7,8,9,10-tetrahydro- (7,10-met-mo) -l, 2,4-lxiazolo [3,4-a] phthalazine; 3-phen-5 - (? Iridin-2-ymetoxy) -l, 2,3a, 4,7-pentaazaddopenta [a] naphthalene; 3-phene-5- (pyridin-2-ρ-p-ethoxy) -l, 2,3a, 4,8-pentaazaddopenta [-.] Naphthalene; 8-metñ-3-ferul-6- (2-p? Dü) methoxy-7,8,9,10-tetiaWdro-l, 2,4-triazolo [3,4-a] phthalazine; 3-phenyl-6- (2-pyridu) methyloxy- (7,8-pentane) -l, 2,4-triazolo [4,3-b] pyridazine; 8,8-dimethy-3-phene-6- (2-? Iridn) methyloxy-7,8,9,10-tetrahydro-l, 2,4-triazolo [3,4-a] phthalazine; 3-Phen-7- (piperidin-1-y) -6 - (? Iridin-2-y-methoxy) -l, 2,4-triazolo [4,3-b]? Iridazine; 3-f enñ-7- (pyridin-4-y) -6- (pyridin-2-ylmethoxy) -l, 2,4-triazolo [4,3-b] pyridazine; 3-phene-5 - (? Mdin-2-ü? Netoxy) -6,7,8,9-tetrahydro-l, 2,3a, 4,8-? Entaaza-cidopenta [ií] naphthalene; 3-phen-5- (pMdin-2-ñ? Netoxy) -6,7,8,9-tetaa dro-l, 2,3a, 4,7-pentaaza-ddopenta [a] naphthalene; 7-methan-3-phenyl-5- (pyridin-2-ümethoxy) -6,7,8,9-tetrahydro-l, 2,3a, 4,7-pentaazaddopenta [n.] Naphthalene; 3-phenyl-6- (pyridin-2-γ-netoxy) -7- (thiophen-2-ü) -l, 2,4-triazolo [4,3-b] pyridazine; 3-fe ?? u-6 ^ (? Din-2-ymetoxy) -7- (thiophen-3-y) -l, 2,4-triazolo [4,3-b] p da --- ina; 3-Fe -6- (2-p dü) methyloxy-7,8,9,10-tetrahydro- (7,10-propane) -l, 2,4-triazolo [3,4-a] phthalazine; 3- (4-methan) phene-6- (2-pyridu) methyloxy-7,8,9,10-tetiahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-ajftalazine; 3- (3-methoxy) phene-6- (2-pMdn) methoxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 3- (2-fluoro) phenyl-6- (2-? Iridu) methyloxy-7,8,9,10-tetiahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a ] phthalazine; 3- (3-pyridine) -6- (2-p dñ) methoxy-7,8,9,10-tetiahydro- (7, lC> -ethane) -l, 2,4-triazolo [3,4- a] phthalazine; 3-ddopropyl-6- (2-? Mdü) methyloxy-7,8,9,10-tettahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] t-azine; 6 - [(6-metñ) -2-pyridu] methyloxy-3-phene-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a ] phthalazine; 6 - [(3-metñ) -2-pmdñ] metuoxy-3-phene-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a ] phthalazine; 6 - [(4-metü) -2-? Irid?] Methoxy-3-fe? Ul-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3, 4-ajftalazine; 6 - [(5-methyl) -2-pyridu] methyloxy-3-phene-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-ajftalazine; 3-phenyl-6- (3-pyridine) methyloxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 3-phenyl-6- (4-pmdü) methyloxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-tthiazolo [3,4-a] phthalazine; 3-Phen-6- [2- (l-methyl) imidazole] methyloxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-ajftalazine; 6- (3-cyanophen) methyloxy-3-phene-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 6- [l- (3 ^ -dimetñ) pirazoM] metuoxy-3-fenü-7,8,9,10-tetiaJrudro- (7,10-ethano) -l, 2,4-triazolo [3,4-a ] phthalazine; 6- [4- (2-methyl) thiazo] methoxy-3-phenyl-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-ajftalazine; 3-phenyl-6- (2-quinoxaHnu) methyloxy-7,8,9,10-tetraMdro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 3-phenyl-6- (3-p dazin) methyloxy-7,8,9,10-tetrah ^ 6- (1-bendHmidazol-2-y) methyloxy-3-phene-7,8,9,10-tetrahydro - (7,10-ethane) -l, 2,4-triazolo [3,4-ajftalazine; 3-phenyl-6- (isoquinoline-N-1-ü) methoxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 6- (1-ethylimidazol-2-y) methyloxy-3-phenyl-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-ajftalazine; 3-phenyl-6- (1-pyrazolon) methoxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 3-phene-6 ^ (? F-? IrroHdin? Carbordl) methoxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-ajftalazine; 6- [4- (3-metü) p? DüJmetüoxy-3-phenyl-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-ajftalazine; 3-Phen-6- (2-quinolin) methoxy-7,8,9,10-tetoahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 6- (2-imidazoM) methoxy-3-phenyl-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phtal-? Z 3-phenyl-6- (2-thiazo) methyloxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-aJ-phthalazine; 6- [2- (5-metü) thiazo] methoxy-3-phene-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-ajftalazine; 6- [2- (4-methyl) thiazoHl] methyloxy-3-phene-7,8,9,10-tetrahydro- (7,10-ethane) -l / 2,4-triazolo [3,4-ajftalazine; 6- [2- (3,5-dimetü) p? Dñ] methoxy-3-phenyl-7,8,9,10-tetiahydro- (7,10-ethane) -l, 2,4-triazolo [3, 4-ajftalazine; 3-phenyl-6- (2-pyrazin) methoxy-7,8,9,10-tetoahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-aJ-phthalazine; 6- [2- (4,6-dimethy) pyridymethoxy-3-phene-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-ajftalazine; 3-phenyl-6- (4-thiazom) methoxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-aJ-phthalazine; 6- [2- (5,6-dimethy) p-methmethyloxy-3-phene-7,8,9,10-tetoahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-ajftalazine; 6- (4-methuimidazol-2-y) methyloxy-3-phene-7,8,9,10-tetiahydro- (7,10-ethano) -l, 2,4-triazolo [3,4-ajftalazine; 3-phenyl-6- (4-? Irimidin?) Methnoxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 6- [4- (2-etü) thiazo jmetüoxi-3-fenñ-7,8,9,10-tetiahidro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phta ^ 6- (6-chloro-mdazin-3-ü) methyloxy-3-phene-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4- ajftalazine; 6- (2-imidazoHl) methyloxy-3- (4-methylphen) -7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-ajftalazine; 6- (4-hydroxymethylphen) methyloxy-3-phene-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-ajftalazine; 6- (4-hydroxybutyl) oxy-3-phene-7,8,9,10-tetrarudro- (7,10-ethane) -l, 2,4-triazolo [3,4-aJphtalazine; 6- (4-Hydroxymethylhexyl) methyloxy-3-phen-7,8,9,10-tetiahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-ajftalazine; 6- (3-hydroxymethylphenyl) methnoxy-3-phenyl-7,8,9,10-tetraMdro- (7,10-ethane) -l, 2,4-triazolo [3,4-ajftalazine; 6- (l-methü-l, 2,4-triazol-3-y) methoxy-3-phenyl-7,8,9,10-tetrahydro- (7,10-ethano) -l, 2,4-triazolo [3,4-ajftalazine; 6- (2-metñ-l, 2,4-triazol-3-ñ) metuoxy-3-phene-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-ajftalazine; 3-phenyl-6- (3-dclo-ropñmetüoxi-2-? Iridñ) methoxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4- a] phthalazine; 3-phenyl-6- (3-ethoxy-2-pyridine) methyloxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-ajftalazine; 6- (6-methypyridin-2-y) methyloxy-3-phen-1, 2,4-triazolo [3,4-a] phthalazine; 6- (l-l-Metn í-l, 2,4-triazol-3-ümetoxi) -3,7-difenñ-l, 2,4-triazolo [4,3-bJ iridazina; 6- (2-methan-2-l, 2,4-triazol-3-methoxy) -3,7-diene: en-1, 2,4-triazolo [4,3-b] pyridazine; 3,7-difenn-6- (2ff-l, 2,4-triazol-3-υmethoxy) -l, 2,4-triazolo [4,3-b-pyridazine; 6- (2-methyl-2 / i-tetiazol-5-ü netoxi?) -3,7-difenü-l, 2,4-triazolo [4,3-BJ iridazina; 3,7-difluo-6- (2-prophen-2/7-l, 2,4-triazol-3-iknetoxy) -l, 2,4-triazolo [4,3-b]? Iridazine; 3,7-difetxñ-6- (l-? Ropü-17? -l, 2,4-triazol-3-ylmethoxy) -l, 2,4-triazolo [4,3-b] pyridazine; 6- (1-methyl-1'-imidazol-4-urea) -3,7-diphenol, 2,4-triazolo [4,3-b-pyridazine; 6- (3-metñ-3 7-imidazol-4-ylmethoxy) -3,7-diflumell-l, 2,4-triazolo [4,3-b] pyridazine; 6- (4-methu-4-Y-1, 2,4-triazol-3-methoxy) -3,7-clifen-1, 2,4-triazolo [4,3-b-pyridazine; 6- (5-methyl-2H-l, 2,4-triazol-3-ümetoxi) -3,7-difenñ-l, 2,4-triazolo [4,3-bJ iridazina; or-is-metU-SII ^^ - ^ -S ^ triazo -ñmetox -difenü-l ^^ - ^ S-triazolo bJpiridazina; 3- (4-methoxifer? Ñ) -6- (l-metñ-li7-l, 2,4-triazol-3-ylmethoxy) -7-fenü-l, 2,4-triazolo [4,3-b] pyridazine; 6 ^ (3-nxetñ? Din-2-ñ? Netoxy) -3-fenñ-7- (piperidin-l-ñ) -l, 2,4-triazolo [4,3-b] pyridazine; 7- (4-n-morfolm) -3-Fenn-6 ^ (PMDIN-2-n netoxi?) -l, 2,4-triazolo [4,3-b] pyridazine; 3-fer? Ü-7 - (? Mdin-3-ñ) -6- (pyridin-2-γ-netoxy) -l, 2,4-triazolo [4,3-b] pyridazine; 8-metñ-6- (2-metñ-2 ^ -l, 2,4-triazol-3-ümethoxy) -3,7-difenñ-l, 2,4-triazolo [4,3-bJpiridazina; 6- (l-metñ-lH-l, 2,4-triazol-3-ñmethoxy) -7- (morpholin-4-ü) -3-phene-l, 2,4-triazolo [4,3-b] ? iridazine; 6- (2-metü-2ff-l, 2,4-triazol-3-ymetoxy) -7- (morpholin-4-y) -3-phenyl-l, 2,4-triazolo [4,3-b] ? iridazine; 7-ddohexñ-6- (2-metñ-2ff-l, 2,4-triazol-3-iknetoxi) -3-fenül-l, 2,4-triazolo [4,3-b] pyridazine; 7-cidohexii-6- (l-metñ-li?: - l, 2,4-triazol-3-ymetoxy) -3-ferul-l, 2,4-triazolo [4,3-b-pyridazine; 7-ddopentin-6 ^ (2-n? Etü-2-r-l, 2,4-thiazole-3-yn? Neatxy) -3-phene-l, 2,4-triazolo [4,3-b] pyridazine; 8-metñ-6- (l-metñ-l-l, 2,4-triazol-3-ümethoxy) -3,7-diffe-t-l, 2,4-triazolo [4,3-b-pyridazine; 7-ddobutñ-6- (l-metü-li7-l, 2,4-thiazol-3-γ-netoxy) -3-phenyl-2,4-taiazolo [4,3-b-pyridazine; 7-tert-buty-6- (2-methan-2-l, 2,4-triazol-3-ylmethoxy) -3-phenyl-2,4-triazolo [4,3-b-pyridazine; 7-ddobutñ-6- (2-metü-2ff-l, 2,4-txiazol-3-ñ? Netoxy) -3-phene-l, 2,4-triazolo [4,3-b] pmdazine; 7-ethan-6- (2-methan-2ff-l, 2,4-triazol-3-ymetoxy) -3-phene-l, 2,4-triazolo [4,3-b] pyridazine; 7-tert-butyl-6- (1-methan-1-yl, 2,4-triazol-3-y-methoxy) -3-fe-yl, 2,4-triazolo [4,3-b-pyridazine; 7-eti-6- (l-metñ-lií-l, 2/4-triazol-3-ylmethoxy) -3-phenü-l, 2,4-triazolo [4,3-b] pyridazine; 7-methan-6- (2-methan-2-γ-l, 2,4-triazol-3-ylmethoxy) -3-phen-1, 2,4-triazolo [4,3-b] pyridazine; 7- (1-metñddobutñ) -6 ^ (2-metü-2 / f-l, 2,4-triazol-3-ymetoxy) -3-fenü-l, 2,4-triazolo [4,3-bjpiridazina; 7-methy-6- (l-metñ-lií-l, 2,4-triazol-3-ümethoxy) -3-fer? Ñ-l, 2,4-triazolo [4,3-bJpiridazina; 7-ddobutne-3-phenyl-6- (2-yl, 2,4-triazol-3-ymetoxy) -l, 2,4-triazolo [4,3-b] pyridazine; ? 7-ddo Entu-6- (p din-2-ylmethoxy) -3- (thiophen-2-ü) -l, 2,4-tiiazolo [4,3-b] Mdazina; 7-Cidopentyl-3- (2,4-difluorophen) -6- (1-methyl-1α-2,4-triazol-3-methoxy) -1,4-triazolo [4,3-b] ] pyridazine; 7-ddopentñ-6- (l-metü-li-r-l, 2,4-triazol-3-ymetoxy) -3- (thiophen-2-yl) -l, 2,4-triazolo [4,3-bjpyridazine; 7-ddopentyl-6- (2-methy-2-pyr-l, 2,4-triazol-3-υmethoxy) -3- (thiophen-2-ü) -l, 2,4-triazolo [4,3-bjpyridazine; 7-dclopentñ-6- (2-metü-2 // - l, 2,4-triazol-3-ümethoxy) -3- (pyridin-4-ü) -l, 2,4-triazolo [4,3- bjpiridazine; 7-ddopentyl-3- (2-fluoroferyl) -6- (l-methyl-1 / -l, 2,4-triazol-3-umethoxy) -l, 2,4-triazolo [4,3-bjpyridazine; 7-ddopentñ-3- (2-fluorofenñ) -6- (2-metñ-2-r-l, 2,4-triazol-3-ñmethoxy) -l, 2,4-triazolo [4,3-bjpiridazina; 7-ddo? Enti-3- (2-fluorofenu) -6 ^ (? Iridin-2-ylmethoxy) -l, 2,4-triazolo [4,3-b] p-Mdazine; 7-ddopentin-3- (2,4-dñluorofenñ) -6- (2-metñ-2íf-l, 2,4-triazol-3-ñmethoxy) -l, 2,4-triazolo [4,3-bjpiridazina; 7-ddopentyl-3-phenyl-6- (p? Dm-2-ylmethoxy) -l, 2,4-triazolo [4,3-b] pyridazine; 7-ddo? Ent-8-methan-6- (2-methy-2-yl, 2,4-triazol-3-ymetoxy) -3-phene-1, 2/4-triazolo [4,3-bjpyridazine; 7-ddopentyl-3-phenyl-6 ^ (2ff-l, 2,4-triazol-3-ylmethoxy) -l, 2,4-triazolo [4,3-b-pyridazine; 3- (4-methyHenu) -7-phene-6- (p-din-2-ümethoxy) -l, 2,4-triazolo [4,3-b]? Iridazine; 3- (4-? Netilfen?) -6- (3-net? P? Din-2-ün? Ethoxy) -7-phene-l, 2,4-triazolo [4,3-b] pyridazine; 6- (l-etñ-l- ¥ -irnidazol-2-ü-netoxy) -3- (4-netñfer? Ü) -7-fenñ-l, 2,4-triazolo [4,3-bJpMdazina; 3-phenyl-6- (ω-din-2-ümethoxy) -7- (thiomorpholin-4-y) -l, 2,4-triazolo [4,3-b-pyridazine; 6- [2- (4-methytiazol-5-ü) ethoxyJ-3,7-diphen-l, 2,4-triazolo [4,3-b] pyridazine; (±) -7- (2-? Net? IrroHdin-l-ü) -3-phen-6- (pMdin-2-ñrnetoxy) -l, 2,4-triazolo [4,3-b]? Iridazine; 6- (l-metü-li-rl, 2,4-triazol-3-ymetoxy) -3-fe? Xu-7- (p? Din-4-y) -l, 2,4-triazolo [4, 3-b] mdazine; 7-ddopentin-6- (l-meth-li-1, 2,4-triazol-3-γ-necnyloxy) -3-phen-1, 2,4-triazolo [4,3-b] pyridine; 7-isopropy-6- (l-rnetñ-li / -l, 2,4-triazol-3-ün? Ethoxy) -3-phenü-l, 2,4-triazolo [4,3-b-pyridazine; 3-cyclopropy-6- (1-methan-li-r-l, 2,4-triazol-3-ymetoxy) -7-phen-1, 2,4-triazolo [4,3-b-pyridazine; 3- (2-fluorophenyl) -6- (2-methan-2 ^ -l, 2,4-triazol-3-ylmethoxy) -7-phene-1, 2,4-triazolo [4,3-b] pyridazine; 3- (2-fluorophenone) -6- (l-methü-l ^ -l, 2,4-triazol-3-ylmethoxy) -7-phen-l, 2,4-triazolo [4,3-b] pyridazine; 6- (l-metü-l / -l, 2,4-triazol-3-ymetoxy) -7-phene-3- (thiophen-2-y) -l, 2,4-triazolo [4,3-b] ] pMdazina; 6- (l-metü-lií-l, 2,4-triazol-3-ylmethoxy) -7-fenfl-3 - (? Iridin-3-ü) -l, 2,4-triazolo [4,3-b-pyridazine; 6- (2-methyl-2-ir-1, 2,4-triazol-3-methoxy) -7-phen-3- (thiophen-2-y) -l, 2,4-thiazolo [4,3-b] ] p? dazina; 6- (2-methyl-2i? -l, 2,4-triazol-3-ylmethoxy) -7-feml-3- (pmdin-3-ü) -l, 2,4-triazolo [4,3-bJpmdazine; 3- (furan-3-y) -6- (l-metñ-l-l, 2,4-triazol-3-ymetoxy) -7-feml-l, 2,4-triazolo [4,3-b] pyridazine; 6- (l-metü-lií-l, 2,4-triazol-3-ylmethoxy) -7-fer? Ü-3- (thiophen-2-ü) -l, 2,4-triazolo [4,3- b]? iridazine; 6- (5-methan-l, 2,4-oxadiazol-3-methoxy) -3,7-diphenol-l, 2,4-triazolo [4,3-b]? Iridazine; 7-phenyl-3- (thiophen-2-y) -6- (2-ylf-l, 2,4-triazol-3-ymetoxy) -l, 2,4-triazolo [4,3-b-pyridazine; 3- (furan-2-y) -6- (l-methyl-li-l, 2,4-triazol-3-ylmethoxy) -7-phen-l, 2,4-triazolo [4,3-b] p dazina; 6- (l-metul-l-l, 2,4-triazol-3-umethoxy) -3-phene-7- (thiophen-3-yl) -l, 2,4-triazolo [4,3-b ] pyridazine; 6- (2-methan-2-l, 2,4-triazol-3-ymetoxy) -7- (thiophen-3-ü) -l, 2,4-triazolo [4,3-b] mdazine; 3-phen-7- (thiophen-3-y) -6- (2 / l-l, 2,4-triazol-3-ylmethoxy) -l, 2,4-thiazolo [4,3-b] pyridazine; 6- (2-methyl-2-l, 2,4-triazol-3-y-methoxy) -3-phene-7- (thiophen-2-yl) -l, 2,4-triazolo [4,3- b] pyridazine; 6 ^ (l-metñ-l / fl, 2,4-triazol-3-ümethoxy) -3-phene-7- (thiophen-2-y) -l, 2,4-triazolo [4,3-b] pyridazine; 7- (furan-2-ü) -6- (2-metñ-2-rl, 2,4-triazol-3-ümethoxy) -3-phen-1, 2,4-triazolo [4,3-bJ? iridazine; 7- (furan-2-y) -6 ^ (l-metñ-l-l, 2,4-thiazol-3-ymetoxy) -3-phene-l, 2,4-triazolo [4,3-b] pyridazine; 6- (3-Rethyl-L, 2,4-oxadiazol-5-y-methoxy) -3,7-diphenol-l, 2,4-triazolo [4,3-b] pyridazine; 3- (4-fluorophenone) -6- (1-methylene-1, 2,4-triazol-3-methoxy) -7-phenyl-2,4-triazolo [4,3-b-pyridazine; 3,7-difenn-6- (2 7-l, 2,3-triazol-4-ymetoxy) -l, 2,4-triazolo [4,3-b]? Iridazine; 3,7-diphen-6- (pyrazin-2-ymetoxy) -l, 2,4-triazolo [4,3-b] pmdazin; 3- (4-metñfenñ) -6- (l-metñ-li-rl, 2,4-tri- zol-3-ylmethoxy) -7-phene-l, 2,4-triazolo [4,3-b ]? iridazine; 6- (4-methylthiazol-2-yl-ethoxy) -3,7-diphen-l, 2,4-triazolo [4,3-b] pyridazine; 6- (5-? -nethiazol-2-ylmethoxy) -3,7-difleml-l, 2,4-triazolo [4,3-b-pyridazine; 3,7-dJ.fenñ-6 - (? Irirnidin-4-ü? Netoxy) -l, 2,4-triazolo [4,3-b] pyridazine; 3,7-difenu-6- (pyridazin-3-υmethoxy) -l, 2,4-triazolo [4,3-b] pyridazine; 6- (l-metñ-l ^ -l, 2,4-txiazol-3-ümethoxy) -7- (morpholin-4-y) -3- (thiophen-2-y) -l, 2,4-triazolo [4,3-bjpiridazine; 3,7-difenu-6- (thiazol-4-ümetsxy) -l, 2,4-triazolo [4,3-b-pyridazine; 6- (5-methysoxazole-3-urea) -3,7-diphenol-l, 2,4-triazolo [4,3-b-pyridazine; 3- (3-fluorophenone) -6- (l-methylene-l, 2,4-triazol-3-y-methoxy) -7- (morpholin-4-y) -l, 2,4-triazolo [4,3 -bjpiridazine; 3,7-diene-6- (pyrimidin-2-ymetoxy) -l, 2,4-triazolo [4,3-b] pyridazine; 6- (2-methy-2ff-1, 2,3-triazol-4-methoxy) -3,7-diphen-l, 2,4-thiazolo [4,3-b] pyridazine; 7- (1-methylatedbutylene) -6- (1-methyl-1 / -l, 2,4-triazol-3-ylmethoxy) -3-phen-1, 2,4-triazolo [4,3-bjpyridazine; 7-isoprop-6- (2-methan-2-yl, 2,4-triazol-3-ylmethoxy) -3-fe-yl-l, 2,4-triazolo [4,3-bJ-iridazine; 7-tert-butyl-3- (2-fluorophenyl) -6- (1-methyl-1-l, 2,4-triazol-3-methoxy) -l, 2,4-triazolo [4,3-bjpyridazine; 7-ddopentin-3- (4-methoxyphenyl) -6- (2-methy-2-yl-l, 2,4-triazol-3-ylmethoxy) -l, 2,4-triazolo [4,3-bjpyridazine; 7- (l-metñdclo? Entñ) -6- (l-metñ-L / Y-l, 2,4-triazol-3-ñmethoxy) -3-phene-l, 2,4-triazolo [4,3- bjpiridazine; 7- (l-metüdclo? Entñ) -6- (2-metñ-2 7-l, 2,4-triazol-3-ümethoxy) -3-fenül-l, 2,4-triazolo [4,3-bjpiridazine; 7-ddopentñ-3- (furan-2-ñ) -6- (2-metü-2 / -l, 2,4-triazol-3-ümethoxy) -l, 2,4-triazolo [4,3-bjpiridazine; 7-ddopentñ-3- (furan-2-y) -6- (l-metñ-l / -l, 2,4-triazol-3-ümethoxy) -l, 2,4-triazolo [4,3-bjpiridazine; 3- (3,7-diphenol-l, 2,4-triazolo [4,3-b] pyridazin-6-üoxirnetü) -l, 2,4-triazole-1-acetonitrile; 7- (l-metñdclopropñ) -6- (2-metñ-2ír-l, 2,4-triazol-3-ymetoxi) -3-fex? Ñ-l, 2,4-triazolo [4,3-bjpiridazina; 7- (1-methycyclopropy) -6- (1-methanyl, 2,4-triazol-3-methoxy) -3-phen-1, 2,4-triazolo [4,3-bjpyridazine; 3- (3-fluorofenu) -6- (l-metñ-l ^ -l, 2,4-triazol-3-ümethoxy) -7-fer-ü-l, 2,4-triazolo [4,3-b ] pyridazine; 7- (1-methyl-4-methylpentyl) -6- (3-methypyridin-2-ihetoxy) - ^^ 6- (1-methan-7-l, 2,3-triazol-4-ylmethoxy) -3,7-diphen -l, 2,4-triazolo [4,3-b-pyridazine; 3- (5-metütiofen-2-ñ) -6- (l-metñ-l -l, 2,4-triazol-3-ümetoxi) -7-fenñ-l, 2,4-triazolo [4,3- bjpiridazine; 2- [3- (3,7-diphen-l, 2,4-triazolo [4,3-b]? Iridazin-6-ylmethylene) -l, 2,4-triazol-1-y] -? ^, -dimethylacetamide; 3,7-difenñ-6- [l- (p din-2-ümetñ) -l-l, 2,4-triazol-3-ümethoxy] -l, 2,4-triazolo [4,3-b]? iridazine; 6- (l-benzyl-l-l, 2,4-triazol-3-ymetoxy) -3,7-diphenol, 2,4-triazolo [4,3-b-pyridazine; 2- [5- (3,7-diphenol-l, 2,4-thiazolo [4,3-b-pyridazin-6-oxymethylene) -l, 2,4-triazol-l-u] acetamide; ? ^ - [2- [3- (3/7-difenn-l, 2,4-triazolo [4,3-bJpmdazin-6 ^ üoximetñ) -l, 2,4-t-riazol-l-ñ] etü ] -? r,? '- dimethylamine; 3,7-diferm-6- (pyrimidin-5-ymetoxy) -l, 2,4-triazolo [4,3-bJ? Iridazine; 6- [l- (2- (morpholin-4-ü) -etü) -lff-l, 2,4-thiazol-3-ymetoxy] -3,7-diflu-l, 2,4-triazolo [4, 3- bjpiridazine; 6- (2-metü-2ff-l, 2,4-triazol-3-ymetoxy) -3-phene-7 - (? IrroHdin-l-ü) -l, 2,4-t-riazolo [4,3 -b-Pyridazine; 7- (5-dorothiophen-2-y) -6- (2-methy-2ff-l, 2,4-triazol-3-yl-methoxy) -3-fe-1-l, 2,4-triazolo [4, 3-bj pyridazine; 7- (5-dorothiophen-2-y) -6- (l-methyl-l-rl, 2,4-triazol-3-ylmethoxy) -3-phenyl-l, 2,4-triazolo [4,3- bjpiridazine; 6- (li? -benzin? Idazol-2-ümethoxy) -3- (2,4-difluoroferul) -7- (1-methycyclopentyl) -l, 2,4-triazolo [4,3-bjpyridazine; 3- (furan-3-y) -6- (2-pyridine) methoxy-7,8,9,10-tetrahydro-l, 2,4-triazolo [3,4-a] phthalazine; 7-cidobutyl-3-phene-6- (prop-2-inoxo) -l, 2,4-triazolo [4,3-b]? Iridazine; (7-Cidobutne-3-phenyl-1, 2,4-triazolo [4,3-b] pyridazin-6-yoxi) acetonitrile; ? ^ - [4- (7-cidobutyl-3-phenyl-1, 2,4-triazolo [4,3-b-pyridazin-6-yoxi) but-2-in-1-γ-r-dirnethylamine; 2- [3- (3,7-diflu-ul-l, 2,4-triazolo [4,3-b-pyridazin-6-n-oxymethyl) -l, 2,4-triazol-1-y] ethylamine; 3,7-difenñ-6- [l- (2- (pyrroHdin-l-ü) etü) -l fl, 2,4-triazol-3-methoxy] -l, 2/4-triazolo [4,3- bjpiridazine; 6- [l- (l-metñ? Iperidin-4-ü) -l // - l, 2,4-triazol-3-ylmethoxy] -3,7-diphen-l, 2,4-triazolo [4, 3-bjpiridazine; 3,7-diflumethyl-6- [l- (2- (piperazin-1-yl) yl) -l, 2,4-triazol-3-ylmethoxy] -l, 2,4-triazolo [4,3- bjpiridazine; 7- (l-metücidopentñ) -6- (2-metü-2H-l, 2,4-triazol-3-ümethoxy) -3- (2,4-dñ? Uorofer? Ü) -l, 2,4- triazolo [4,3-bJ pyridazine; 7- (ddobut-l-enñ) -6- (2-metü-2-l, 2,4-triazol-3-ylmethoxy) -3-fe-ul-l, 2,4-lthiazolo [4,3- bPyridazine; 7- (furan-3-ü) -6- (l-metul-l-l, 2,4-triazol-3-ymetoxy) -3-phene-l, 2,4-triazolo [4,3-b ]? iridazine; W-diet? - ^ ó-l-methyl-l / l-l ^ - ^ üjamina; 7- (1-metidodilpentyl) -6- (1-methan-1-Y-1, 2,4-triazol-3-ytoxy) -3- (2, 4-dluorofenu) -l, 2,4- triazolo [4,3-b] pyridazine; 7- (l, l-dimetü? Ro? Ü) -6- (l-metü-l 7-l, 2,4-triazol-3-ñmethoxy) -3-fenül-l, 2,4-triazolo [4 , 3-bjpiridazine; 6- (2-metü-2 í-l, 2,4-taiazol-3-ñmethoxy) -3- (4-fluorofenñ) -7- (thiophen-3-ü) -l, 2,4-triazolo [4 , 3-bjpiridazine; 6- (l-metñ-li7-l, 2,4-tariazol-3-ihnetoxi) -3- (4-fluorofenñ) -7- (thiophen-3-ü) -l, 2,4-triazolo [4, 3-bjpiridazine; 6- (2-metñ-2íT-l, 2,4-triazol-3-ümethoxy) -3- (2-fluorofenñ) -7- (thiophen-3-y) -l, 2,4-triazolo [4, 3-bjpiridazine; 3- (2-fluorophenone) -7- (1-methylenbutyl) -6- (2-methan-2/1-l, 2,4-triazol-3-methoxy) -l, 2,4-triazolo [4, 3-bjpiridazine; 3- (2-fluorophenone) -7- (1-methylenbutylene) -6- (1-methyl-1-rl, 2,4-triazol-3-methoxy) -l, 2,4-triazolo [4,3- bjpiridazine; 6- (l-metü-l / -l, 2,4-triazol-3-ymetoxy) -3- (2-fluorofenü) -7- (thiophen-3-y) -l, 2,4-triazolo [4 , 3-bjpiridazine; 8-metü-7- (l-metñcidobutü) -6- (l-metñ-l /? - l, 2,4-triazol-3-ümethoxy) -3-fenñ-l, 2,4-triazolo [4, 3-bjpiridazine; 8-metñ-7- (l-metücidobutñ) -6- (2-metü-2 í-l, 2,4-triazol-3-ylmethoxy) -3-fenül-l, 2,4-triazolo [4,3 -bjpiridazine; 6- (l-metü-l ^ -l, 2,4-triazol-3-ylmethoxy) -3-fer-ü-7- (pyrroHdin-l-ñ) -l, 2,4-triazolo [4,3 -b-pyridazine; 7-ddobutyl-8-metñ-6- (2-metñ-2 f-l, 2,4-triazol-3-ümethoxy) -3-phene-l, 2,4-triazolo [4,3-bj pyridazine; 7-ddobutyl-8-methan-6- (l-met-l-lyl / -l, 2,4-triazol-3-umethoxy) -3-phenyl-l, 2,4-triazolo [4,3-bjpyridazine; 7- (l-metüddopentñ) -6- (2-metü-2ff-l, 2,4-thiazol-3-ymetoxy) -3- (2-fluorofenü) -l, 2,4-triazolo [4,3- bjpiridazine; 7- (l-metücidopentü) -6- (l-methyl-lií-l, 2,4-triazol-3-ümethoxy) -3- (2-fluorofenñ) -l, 2,4-triazolo [4,3- bjpiridazine; 7-ddobutu-6- [4- (2,6-di? Neñrnorfolin-4-ü) but-2-innoxy] -3-phene-l, 2,4-triazolo [4,3-b]? Iridazine; and the salts and prodrugs thereof. The present invention also proposes a method for the treatment and / or prevention of anxiety, which comprises administering to a patient in need of said treatment an effective amount of a compound of formula I, as defined above, or a salt thereof or pharmaceutically acceptable prodrugs. The present invention also provides a method for the treatment and / or prevention of seizures (e.g., in a payer suffering from epinepsy or a relapsed disorder, which comprises administering to a payer in need of such treatment an effective amount of a compound of Formula I, as defined above, or one of its pharmaceutically acceptable salts or prodrugs In another aspect, the present invention provides a non-sedating anxiogenic compound which is a modulator of the benzodiazepine binding site of the human GABAA receptor, which has a binding affinity (K) for the o3 subunit of the human GABAA receptor of 10 nM or less, which induces an enhancement of at least 40% of the EC20 GABA response in stably transferable recombinant cell lines that express the a3 subunit of the human GABAA receptor and that induces at most a potendadon of 30% of the EC20 GABA response in transferable cell lines s stably expressing the subunit to the human GABAA receptor. In this aspect of the invention, the binding affinity (K) of the compounds for the ot3 subunit of the human GABAA receptor is as conveniently measured by the assay described below. The binding affinity (Ki) to the oc3 subunit ( K) of the compounds fulfilling this aspect of the invention is 10 nM or less, preferably 2 nM or less, and more preferably 1 nM or less.

In this approach, the enhancement of the EC20 GABA response in stably transfected cell lines expressing the oc3 subunits and that of the human GABAA receptor can be conveniently measured by procedures analogous to the protocol described in Wafford et al., Mol. Pharmacol., 1996, 50, 670-678. The procedure will be carried out suitably using cultures of stably transfected eukaryotic cells, typically stably translocated Ltk fibroblast cells. Compounds which comply with this aspect of the invention will induce an enhancement of at least 40%, preferably at least 50%, and more preferably at least 60% of the EC20 GABA response in transfectant cell lines that are transfected in a stable manner that express the a3 subunit of the human GABAA receptor. In addition, compounds complying with this aspect of the invention will induce a maximum potentiation of 30%, preferably at most 20%, and more preferably at most 10% of the EC20 GABA response in stably transfected cell lines expressing the subunit to the human GABAA receptor. The compounds fulfilling this aspect of the invention exhibit anxious activity, as demonstrated by a positive response in high labyrinth and conditional suppression drinking tests (see Dawson et al., Ps chopharmacology, 1995, 121, 109-117). . In addition, compounds that comply with this aspect of the invention are basically non-sedative, as confirmed by an appropriate result obtained from the response-synbience test (pull a chain) (see Bayley et al., J. Psychopharmacol ., 1996, 10, 206-213). The compounds that comply with this aspect of the invention also have anticonvulsant activity. This is demonstrated by its ability to block seizures induced by pentanetetrazol in rats and mice, following a protocol analogous to that described by Bristow et al. in /. Pharmacol. Exp. Ther., 1996, 279, 492-501. In order to achieve its efedos on behavior, the compounds that comply with this aspect of the invention will penetrate the brain, in other words, the compounds will be able to cross the so-called "heme barrier". Preferably, the compounds that comply with this aspect of the invention will be able to exercise their beneficial therapeutic action after oral administration. A representative compound that fulfills this aspect of the invention is 7-cidobutne-6- (2-methan-2-l, 2,4-thiazole-3-methoxy) -3-phene-1, 2,4-triazolo [4 , 3-bJ? Iridazine. In a further aspect, the present solidity addresses a method for screening non-sedating anxiogenic compounds comprising: (1) contacting a group of test compounds with (a) a line of stably transfected recombinant cells expressing the a3 subunit of the human GABAA receptor; and (b) a line of stably transfected recombinant cells expressing the subunit to the human GABAA receptor; (2) measuring the potency of the EC20 GABA response induced by each of the test compounds in each of the cell lines stably transfected (a) and (b); and (3) selecting those test compounds that achieve at least a 40% enhancement of the EC20 GABA response in the cell line expressing the a3 subunit and at most a 30% enhancement of the EC20 GABA response in the line of cells that the subunit expresses al. The invention also proposes pharmaceutical compositions comprising one or more of the compounds of this invention combined with a pharmaceutically acceptable carrier. Preferably, these compositions are in dosage unit forms such as tablets, lozenges, capsules, powders, granules, solutons or sterile parenteral suspensions, liquid or aerosol spray with metered doses, drops, ampoules, self-injecting devices or suppositories; for oral, parenteral, intranasal, sublingual or rectal administration or for administration by inhalation or insufflation. To prepare composition As the tablets, the active ingredient prindpal is mixed with a pharmaceutical carrier, for example, ingredients of convendonal tablets such as corn starch, steroid, sucrose, sorbitol, talc, stearic acid, magnesium stearate, dicralde phosphate or gums, and others. pharmaceutical solvents, e.g., water, to form a solid preformulation composition containing a homogeneous mixture of a compound of the present invention, or one of its pharmaceutically acceptable salts. When these preformulation compositions are referred to as being homogeneous, it is indicated that the adi-ve ingredient is dispersed homogeneously throughout the composition so that the composition can be easily subdivided into equally effective dosage unit forms, as compounds. , pills and capsules. This single-form preformulation composition is then subdivided into dosage unit forms of the type described above containing from 0.1 to about 500 mg of the active ingredient of the present invention. Typical dosage unit forms contain from 1 to 100 mg, for example 1, 2, 5, 10, 25, 50 or 100 mg, of the active ingredient. The tablets and lozenges of the new composition can be coated or otherwise prepared to provide a dosage form that provides the benefits of prolonged acdone. For example, the tablet or tablet may comprise an internal dosage component and an external dosage component, the latter being in the form of a shell over the former. The two components can be separated by an enteric layer that serves to resist disintegration in the stomach and allows the internal component to pass into the innate duodenum or delay its Hberadon. A variety of materials can be used for such enteric layers or coatings. Such materials include a series of polymeric acids and mixtures of polymeric acids with materials such as shellac, ketonic alcohol and cellulose acetate. The liquid forms in which the new compositions of the present invention can be incorporated for oral administration or injection include aqueous solutions, suitably flavored syrups, aqueous or oily suspensions and aromatic emulsions. tinged with edible oils such as cottonseed oil, sesame oil, coconut oil or peanut oil, as well as elixirs and similar pharmaceutical vehicles. Suitable dispersing or suspending agents for aqueous suspensions induce synthetic and natural gums such as gum tragacanth, gum arabic, alginate, dextran, sodium carboxymethyl cellulose, methyl cellulose, polyvinyl pyrrodonone and gelatin. In the treatment of anxiety, an appropriate dose level ranges from about 0.01 to 250 mg / kg per day, preferably from about 0.05 to 100 mg / kg per day and especially from about 0.005 to 5 mg / kg. per day. The compounds can be administered according to a schedule of 1 to 4 times per day. The compounds of formula I, as defined above, can be prepared by a process comprising reacting a compound of formula III with a compound of formula IV: (III) (IV) wherein Y, Z, R1 and R2 are as defined above; and L1 represents a suitable safe group. Typically, the saHente group L1 is a halogen atom, especially doro. The reaction between compounds III and IV is carried out conventionally by stirring the reactants in a suitable solvent, typically,? ? ^ dimetñ-formamide, in the presence of a strong base such as sodium hydride or bis (trimethylsihl) amide of Hcy. The intermediates of formula III above can be prepared by reacting a compound of formula V with a substantially equimolar amount of a hydrazine derivative of formula VI: (V) (VI) wherein Y, Z, R1 and L1 soh as defined above and L2 represents a suitable safe group; followed, if necessary, by the separation of the resulting mixture from the isomers by conventional means. Typically, the halogen group L2 is a halogen atom, especially chlorine. In the intermediates of formula V, the leaving groups L1 and L2 may be the same or different, although suitably they will be the same, preferably both chlorine. The reaction between compounds V and VI is conveniently effected by heating the reactants in the presence of a base such as triethylamine, typically under reflux in an inert solvent such as xylene or 1,4-dioxane. When Y and Z are different, the reaction between the compounds V and VT will provide, as indicated above, a mixture of isomer products, depending on whether the hydrazine derivative VI displaces the leaving group L1 or L2. Thus, in addition to the required probod of formula III, the compound in which the Y and Z moieties are inverted will normally be obtained in a certain amount. For this reason, it will usually be necessary to separate the resulting mixture of isomers by convendonal methods such as chromatography. In another process, compounds of formula I, as defined above, can be prepared by a process comprising reacting a compound of formula VII with a compound of formula VIII: (VII) (VIII) wherein Y, Z, R1 and R2 are as defined above; and L3 represents a suitable safe group. Typically, the saHente group L3 is a halogen atom, typically doro or bromine. The reaction between compounds VII and VTII is conveniently effected by stirring the reactants in a suitable solvent, typically fTV-dimethylamide in the presence of a strong base such as sodium hydride. The intermediate of formula VII above can conveniently be prepared by reacting a compound of formula III, as defined above, with an alkali metal hydroxide, for example sodium hydride. The reaction is conveniently carried out in an inert solvent such as aqueous 1,4-dioxane, ideally at the reflux temperature of the solvent. In a further process, the compounds of formula I, as defined above, can be prepared by a process comprising reacting a compound of formula Z-CO2H with a compound of formula IX: (IX) wherein Y, Z, R1 and R2 are as defined above; in the presence of silver nitrate and ammonium persulfate. The reaction is conveniently carried out under acidic conditions in a suitable solvent, for example, using sulfuric acid in water or aqueous acetonitrile, typically at an elevated temperature. The intermediates of formula IX correspond to the compounds of formula I, as defined above, in which Z is hydrogen and can therefore be prepared by procedures analogous to those described above for preparing the corresponding compounds of formula I. In another adidonal aspect, the compounds of formula I, as defined above, can be prepared by a process comprising reacting a compound of formula X with a compound of formula XI: (X) (XI) wherein Y, Z, R1 and R2 are as defined above, Alk represents an alkano group C? -6, typically "-butyl, and L4 represents a suitable saHente group; in the presence of a catalyst of a transition metal. The leaving group L4 is suitably a halogen atom, for example bromine. A transition metal catalyst suitable for use in the reaction between compounds X and XI comprises dichlorobis (triphenphosphine) -palladium (II). The reaction between compounds X and XI is conveniently carried out in an inert solvent such as? JV-dimethylformamide, typically at an elevated temperature. Intermediates of formula X can be prepared by reacting a compound of formula IV, as defined above, with a compound of formula XII: (XII) wherein Y, Z, L1 and L4 are as defined above; in analogous conditions gas to those described above for the reaction between compounds m and IV. When these are not commercially available, the starting materials of formula IV, V, VI, HIV, XI and XII can be prepared by procedures analogous to those described in the appended Examples, or by well -conventional convention procedures. in the technique. It will be understood that any compound of formula I obtained initially from any of the above processes, when appropriate, will be subsequently processed to another compound of formula I by techniques known in the art. For example, a compound of formula IJ or IK, as defined above, in which R3 is hydrogen, can be subjected to a cata- lytic hydrogenation using conventional conditions, providing the corresponding compound of formula IG or IH, respectively, wherein R4 is hydrogen . In addition, a compound of formula IG or IH can be converted, as defined above, wherein R4 is hydrogen in the corresponding compound wherein R4 is Ci-β alk by a conventional reducing alkylation process, for example, by the treatment with the appropriate aldehyde or ketone in the presence of a reductive agent such as sodium cyanoborohydride. Likewise, a compound of formula I, initially obtained, in which R2 is unsubstituted, can be converted into a corresponding compound in which R2 is substituted, typically by conventional methods of accretion, for example, by the treatment with a haloalkyl derivative in the presence of sodium hydride and A A-dimethylformamide, or with a hydroxyalkyl derivative in the presence of triphenphosphine and diethyl azodicarboxylate. In addition, a compound of formula I, initially obtained in which R2 represents damage (Ci-β alk), can be converted into the corresponding analog of 1,2,4-triazole-5-ü (Ci-β alk) 3 substituted , by treatment with the appropriate acñ hydrazine derivative in the presence of a base such as sodium methoxide. Similarly, a compound of formula I initially obtained in which R2 represents an op-donally substituted propargue residue can be converted into the corresponding 2,3-triazolylmethyl analogue by a treatment with azide anion. A compound of formula I can be converted, initially obtained in which the substituent R2 is substituted by a halogen atom, for example doro, in the corresponding compound in which the substituents R 2 are substituted by a di (alk) -6 amino) residue by treatment with the di (alk? C6) appropriate amine, typically, by heating in a solvent such as 1,4-dioxane in a sealed tube. When the processes described above for the preparation of the compounds according to the invention give rise to mixtures of stereoisomers, these stereoisomers can be separated conveniently by conventional techniques such as preparation chromatography. The new compounds can be prepared in racemic form, or the individual enantiomers can be prepared, either by enantiospecific synthesis or by resoludon. The new compounds can, for example, be resolved into their individual enantiomers by conventional techniques such as preparadon HPLC or the formation of the diastereomer pairs with an optically active acid, such as (-) - di - / - toluoñ-d-tartaric acid and / or áddo (+) - di-p-toluoü-l-tartaric, followed by the fractionated crystallization and the generation of the base Hbre. The new compounds can also be resolved by the formation of diastereomeric esters or amides, followed by chromatographic separation and removal of the asymmetric auxiliary compound. During any of the above synthesis sequences, it may be necessary and / or desirable to protect sensitive or reactive groups from any of the molecules impH-lated. This can be achieved by means of conventional protecting groups, such as those described in Protective Groups in Organic Chemistry, ed. J.F.W. McOmie, Plenum Press, 1973; and T.W. Greene & P.G.M. Wuts, Protective Groups in Organic Synthesis, John Winey & Sons, 1991. The protecting groups can be removed at any convenient later stage using procedures as are known in the art. The following Examples illustrate the preparation of the compounds according to the invention.

The compounds according to the present invention inhibit potentially the binding of [3 H] -flumacenin to the benzodiazepine binding site of human receptors.

GABAA containing the a2 or a3 subunit stably expressed in Ltk- cells.

Reagents • Phosphate buffered saline (PBS). • Assay buffer: KH2PO410 mM, 100 mM KCl, pH 7.4 at room temperature. • [3HJ-Flumacense (18 nM for alß3? 2 cells, 18 nM for a2? 3? 2 s cells, 10 nM for a3? 3? 2 cells) in assay buffer. • 100 μM Flunitrazepam in assay buffer. • Cells resuspended in assay buffer (1 tray up to 10 ml).

Collection of the cells The supernatant fluid is separated from the cells. PBS (approximately 20 ml) is added. The cells are scraped and placed in a 50 ml centrifuge tube. The procedure is repeated with another 10 ml of PBS to ensure that most of the cells are separated. The cells are pelleted by centrifuging for 20 minutes at 3,000 rpm in a centrifuge and then frozen if desired. The pellets are resuspended in 10 ml of buffer per tray (25 cm x 25 cm) of cells.

Testing It can be carried out in 96-well plates or in tubes. Each tube contains: • 300 μl of assay buffer. • 50 μl of [3 H] -flumacenum (final concentration for alβ3? 2: 1.8 nM; for a2β3? 2: 1.8 nM; for a3β3? 2: 1, 0 nM). • 50 μl of buffer or solvent vehicle (eg, 10% DMSO) if the compounds are di- they deposit in DMSO at 10% (total); test compound or flunitrazepam (to determine non-specific binding), final concentration 10 μM. • 100 μl of cells The test samples are incubated for 1 hour at 40 ° C, then fumed using a Tomtec or Brandel cell harvester on GF / B filters, followed by 3 x 3 ml washings with assay buffer cooled in ice. The filters are dried and counted by liquid scintillation. The expected values for the total binding are 3000-4000 dpm for the total counts and less than 200 dpm for the non-specific binding if liquid scintillation counting is used, or 1500-2000 dpm for the total counts and less than 200 dpm for the total counting. non-specific binding, if counting is done with scintillation sóHdo Meltñex. The binding parameters are determined by nonlinear least squares regression analysis, from which the inhibition constant K i can be calculated for each of the test compounds. The compounds of the accompanying Examples were tested with the above assay, and all were found to possess a Ki value for the displacement of [3HJRo 15-1788 from subunit a2 and / or a3 of the human GABAA receptor of 100 nM or less .

EXAMPLE 1 3-PhenyI-6- (2-pyridyl) methyloxy-7,8,9a-tetrahydro- (7,10-ethane) -l, 2,4-triazolof3,4-a1phtalazine a) 4,5-Diazatricide [6.2.2.2, 7) dodec-2 (7-Vene-3,6-dione Bicido [2.2.2] od-2-ene-2,3-dicarboxylic acid anhydride (prepared as described in J. Org. Chem., 1993, 6740-6744) (60.8 g, 0.342 mol) in 50% aqueous acetic acid (1600 ml) with sodium acetate trihydrate (55.5 g, 1.2 eq. mol) and hydrazine hydrate (19.82 ml, 1.2 eq mol) The reaction mixture was heated to reflux for 16 hours and then allowed to cool.The produced product was collected by filtration and washed with water and ether. before drying in an oven at 80 ° C, forcing the required product (59.3 g, m.p. = 214 ° C). ? NMR (Proton Nuclear Magnetic Resonance) (250 MHz, DMSO) d 1.16 (4H, d, J = 7.1 Hz), 1.69 (4H, d, J = 7.1 Hz), 3.18 (2H, s), 11.31 (2H, broad s, NH); MS (Mass Pedroscopy) (ES +) m / e 193 [MH] +. b) 3,6-Diene-4,5-diazatricyclo [6.2.2.Z 7 | dodeca-2 (7), 3,5-triene The product of Example 1, Step a) (59.2 g) was dissolved in phosphorus oxidoride (300 ml) and refluxed for 14 h. The solvent was removed in vacuo and azeotroped with 2x toluene. The residue was dissolved in dichloromethane (200 ml) and stirred rapidly and the solution was neutralized by the addition of aqueous sodium bicarbonate and sodium (carefully). When the effervescence ceased, the organic layer was separated and the aqueous layer was extracted with dichloromethane (2 × 200 ml). The combined layers were dried (MgSO 4), filtered and evaporated to afford the desired product (59.5 g, m.p.> 370 ° C). * H NMR (250 MHz, CDCb) d 1.39 (4H, d, J = 8.1 Hz), 1.92 (4H, d, J = 8.1 Hz), 3.47 (2H, s); MS (ES +) m / e 229 [MHJ +. c) 6-Chloro-3-phene-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-aJphtalazine The product of Example 1, Step was suspended b) (2.5 g, 0.011 mol) in xylene (50 ml) with benzohydrazine (1.65 g, 1.1 eq mol) and triethyl amine (1.68 ml, 1.1 eq mol) and the reaction mixture it was heated to reflux for 6 days. The solvent was removed at high vacuum and the residue was purified by chromatography on silica gel using 0-50% ethyl acetate as eluent, followed by recrystallization from ethyl acetate / hexane, affording the desired product (1.3 g. , mp = 186-188 ° C). ? NMR (250 MHz, CDCI3) d 1.43-1.59 (4H, m), 1.91-2.05 (4H,), 3.57 (HH, s), 4.07 (HH, s) , 7.58 (3H, m), 8.58 (2H, dd, J = 7.8 and 1.5 Hz); MS (ES +) m / e 311 [MHJ +. Analysis calculated C, 65.56; H, 4.83; N, 17.74. C17H15CIN4 requires C, 65.70; H, 4.87; N, 18.03%. d) 3-Phen-6 ^ (2-pMdfl) methyloxy-7,8,9,10-tetiahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-alftalazine Sodium hydride was added (0.113 g of a 60% dispersion in oil, 1.75 eq mol) was added to a solution of 2-pyridylcarbinol (0.263 ml, 0.0024 mol) in DMF (20 ml), and the reaction mixture was stirred at room temperature. environment for 15 minutes. After this time, the product of Example 1, Step c) (0.5 g, 0.0016 mol) was added and the reaction mixture was stirred at room temperature for 1 hour. Water was added until the solution became turbid and then stirred for another 15 minutes, a solution was collected by filtration. This solid was recrystallized from ethyl acetate, yielding the desired product (0.112 g, m.p. = 196-198 ° C). ? NMR (360 MHz, CDCk) d 1.45 (4H, m), 1.95 (4H, m), 3.58 (H, s), 4.00 (H, s), 7.26 (H, m), 5.48 (2H, s), 7.44-7.53 (4H, m), 7.77 (IH, m), 8.40 (2H, dd, J = 7.8 and 1, 5 Hz), 8.68 (1H, m); MS (ES +) m / e 384 [MH] +. Analysis calculated C, 71.76; H, 5.54; N, 18.03. C 24 H 21 N 5 O requires C, 72.04; H, 5.52; N, 18.26%.

EXAMPLE 2 3,7-Diphenyl-6- (2-pyridyl) methyloxy-l, 2,4-triazolo [4,3-blpyridazine This compound was prepared using the procedures described in Example 1, Steps a), b), c) and d), using phenylmaleic anhydride in place of the anhydride of the acid bike-clo [2,2,2] od-2-eno- 2,3-dicarboxy in Stage a). The 7-phenus isomer produced in Step c) was lowered lower in the TLC (thin layer chromatography) analysis than the 8-phenyl isomer and thus, the separation of the regioisomers was carried out in this step by chromatography on silica gel using 0-5% ethyl acetate in dichloromethane as eluent. Data for the title compound: p.f. = 203 ° C. ? NMR (360 MHz, CDCfe) d 5.65 (2H, s), 7.24 (HH, m), 7.34 (HH, d, J = 7.8 Hz), 7.53 (6H, m) , 7.69 (3H, m), 8.07 (HH, s), 8.41 (2H, d, J = 6.6 Hz), 8.65 (HH, m); MS (ES +) m / e 380 [MH] +. Analysis calculated C, 72-59; H, 4.47; N, 18.04. C23H17N5O requires C, 72.81; H, 4.52; N, 18.46%.

EXAMPLE 3 3-Phenyl-6- (2-pyridyl) methyloxy-7,8,9,10-tetrahydro-l, 2,4-triazolof 3,4-alftalazine This compound was prepared using the procedures described in Example 1, Steps a), b), c) and d), using tetrahydrophthalic anhydride in place of the bi-ddo [2.2.2] oct-2-ene-2 anhydride, 3-dicarboxy in Stage a). Data for the title compound: p.f. = 194 ° C. ? NMR (360 MHz, CDCl 3) d 1.94 (4H, m), 2.74 (2H, m), 3.14 (2H, m), 5.56 (2H, s), 7.27 (1H, m), 7.47 (4H, m), 7.73 (1H, m), 8.36 (2H, á, J = 6.6 Hz), 8.66 (1H, m); MS (ES +) m / e 358 [MH] +. Calculated analysis C, 70.50; H, 5.25; N, 19.27. C 21 H 19 N 5 O requires C, 70.57; H, 5.76; N, 19.59%.

EXAMPLE 4 7,8-Pimethyl-3-phenyl-6- (2-pyridyl) -neti-Ioxy-l, 2,4-triazolof 4, 3-blpiridazine This compound was prepared using the procedures described in Example 1, Steps c) and d), using 3,6-dichloro-4,5-dimethy-iridazine instead of 3,6-dichloro-4,5-diazatricide [6.2.2.2.7 \ dodeca-2 (7), 3,5-triene in stage c). Data for the title compound: p.f. = 185 ° C. ? NMR (360 MHz, CDCl 3) d 2.35 (3H, s), 2.69 (3H, s), 5.58 (2H, s), 7.27 (1H, m), 7.47 (4H, m), 7.75 (HH, ddd, J = 7.8, 7.8 &1.8 Hz), 8.37 (2H, d, J = 7.6 Hz), 8.65 (HH, m); MS (ES +) m / e 332 [MH] +. Analysis calculated C, 68.38; H, 4.82; N, 20.64. C19H17N5O requires C, 68.87; H, 5.17; N, 21.13%.

EXAMPLE 5 7-Me il-3-phenyI-6- (2-pyridyl) methyloxy-l, 2,4-triazolo [4,3-blpyridazine This compound was prepared using the procedures described in Example 1, Step pas c) and d), using 3,6-dichloro-4-methylpyridazine instead of 3,6-dimer-4,5-diazatridclo [6.2.2.2.7] dodeca-2 (7), 3,5-triene in Stage c). The 7-methyl isomer produced in Step c) decreased lower in TLC than the 8-methyl isomer, and therefore, the separation of the regioisomers was carried out in this step using chromatography on silica gel using 0- 0 ethylacetate. 10% in didoromethane as eluent. Data for the title compound: p.f. = 199 ° C. ? NMR (360 MHz, CDCk) d 2.42 (3H, s), 5.59 (2H, s), 7.28 (HH, m), 7.49 (4H, m), 7.76 (ΔI, ddd, J = 7.8, 7.8 &1.8 Hz), 7.83 (ΔI, s), 8.37 (2H, d, J = 7.6 Hz), 8.65 (ÍH, m); MS (ES +) m / e 318 [MHJ +. Calculated Analysis C, 68.09; H, 4.31; N, 22.01. C? 8H? 5N50 requires C, 68.12; H, 4.76; N, 22.06%.

EXAMPLE 6 Bis-hydrochloride of 7-Ethyl-3-phenyl-6- (2-? Iridipmethyl-d-l, 2,4-triazolof4.3-b1-pyridazine This compound was prepared using the procedures described in Example 1, Steps a), b), c) and d), using maleic anhydride (Synth Commun., 1990, 2491) in place of bicyclo-anhydride [2.2.2 Jod- 2-ene-2,3-dicarboxy in Stage a). The 7-ethyl isomer produced in Step c) decreased lower in the TLC than the 8-etho isomer, whereby the separation of the regioisomers was carried out in this step by chromatography on silica gel using ethyl acetate 0-10 % in didoromethane as eluent. Data for the title compound: p.f. = 193 ° C. ? NMR (360 MHz, DMSO) d 1.31 (3H, t, J = 7.4Hz), 2.81 (2H, q, J = 7.4Hz), 5.85 (2H, s), 7.58 (3H, m), 7.80 (HH, m), 7.99 (HH, d, J = 7.9 Hz), 8.23 (3H, m), 8.34 (HH, m), 8 , 84 (ÍH, d, J = 4.7 Hz); MS (ES +) m / e 332 [MH] +. Analysis calculated C, 56.20; H, 4.53; N, 17.28. C19H17N5O.2HCl requires C, 56.45; H, 4.74; N, 17.32%.

EXAMPLE 7 7,8-Benzo-3-phenyl-6- (2-pyridiI)? NetHoxi-7,8,9,10-tetrahydro-1,2,4-triazolof3,4-alftalazine This compound was prepared using the procedures described in Example 1, Steps a), b), c) and d), using 3,4-dihydro-1,2-naptalenedicarboxylic acid anhydride in place of the bicyclo [2.2. 2Jod-2-ene-2,3-dicarboxy in Stage a). The 7,8-benzo isomer produced in Step c) was lower in TLC than the 9,10-benzo isomer and therefore, the separation of the regioisomers was carried out in this step by chromatography on silica gel using sodium acetate. ethyl 0-30% in dichloromethane as eluent. Data for the title compound: p.f. = 240 ° C. ? NMR (360 MHz, CDCls) d 3.02 (2H, t, J = 7.9 Hz), 3.38 (2H, t, J = 7.9 Hz), 5.74 (2H, s), 7 , 31 (4H, m), 7.51 (4H, m), 7.74 (HH, m), 8.37 (3H, m), 8.71 (HH, m); MS (ES +) m / e 406 [MH] +. Calculated Analysis C, 73.81; H, 4.48; N, 16,%. C25H19N5O requires C, 74.06; H, 4.72; N, 17.27%.

EXAMPLE 8 8-Methyl-3,7-diphenyl-6- (2-pyridyl) methoxy-l, 2,4-triazol-4,3-blpyridazine This compound was prepared using the procedures described in Example 1, Steps a), b), c) and d) using 3-methyl-4-pheuvic anhydride in place of the anhydride of the acid bicido [2.2.2] od- 2-ene-2,3-dicarboxy in Stage a). The 7-phenyl-8-methyl isomer was lower in the TLC than the 7-methyl-8-pheno isomer and therefore, the separation of the regioisomers in this step was effected by chromatography on silica gel using ethyl acetate. -15% in dichloromethane as eluent. Data for the title compound: p.f. = 182 ° C. 1 NMR (360 MHz, DMSO) d 2.45 (3H, s), 5.50 (2H, s), 7.30 (2H, m), 7.54 (8H, m), 7.77 (1H) , m), 8.25 (2H, d, J = 7.8 Hz), 8.58 (1H, m); MS (ES +) m / e 394 [MHJ +. Analysis calculated C, 72.05; H, 4.94; N, 16.55. C24Hi9N5O, 0.5 E OAc. requires C, 72.27; H, 5.09; N, 16.86%.

EXAMPLE 9 (±) -3-Phenyl-6-f2-pyridyl) methyloxy-7,8,9,10-tetrabidro-.7,10-methane) -l, 2,4-triazolof3,4-alftalazine This compound was prepared using the procedures described in Example 1, Steps a), b), c) and d), using 2-norbornene-2,3-dicarboxycoxy anhydride in place of the anhydride of the bicyclo [2.2.2Joct-2- eno-2,3-dicarbox £ Hco in Stage a). Data for the title compound: p.f. = 182 ° C. ? NMR (360 MHz, CDCk) d 1.31 (2H, m), 1.69 (ΔI, d, J = 9.2 Hz), 1.95 (ΔI, d, J = 9.2 Hz), 2 , 12 (2H, m), 3.76 (HH, s), 4.14 (HH, s), 5.59 (2H, s), 7.28 (HH, m), 7.48 (4H, m), 7.76 (HH, m), 8.36 (2H, d, J = 7.8 Hz), 8.68 (HH, m); MS (ES-) m / e 370 [MH] +. Calculated Analysis C, 71.53; H, 5.18; N, 18.96. C22H19N5O requires C, 72.08; H, 5.13; N, 18.89%.

EXAMPLES 10 and 11 3-Phenyl-5-pyridin-2-ylmethoxy) -l, 2,3a, 4,7-pentaazacyclopentallnaphthalene > 0.25 Hydrate v 3-Phenyl-5-pyridin-2-ylmethoxy) -l, 2,3a, 4,8-pentaazacictopentafalna taleno-0,5 Hydrato a) 5-Chloro-3-phene-1, 2,3a, 4,7-? entaazacyclopenta [t.naphthalene and 5-chloro-3-phene-1, 2,3a, 4,8-pentaazacyclopentafgjnaphthalene This mixture 1: 1 of doroimidates was prepared using the procedures described in Example 1, Steps a), b) and c), using 3,4-pyridinedicarboxylic anhydride in place of the anhydride of bicido acid [2.2.2Jod-2-ene-2,3- dicarboxy Data for the mixture: JH NMR (250 MHz, CDCl 3) d 7.54-7.62 (3H, m), 8.04 (0.5H, dd, J = 7.3, 1.5 Hz), 8 , 38-8.46 (2H, m), 8.71 (0.5H, dd, J = 7.3, 1.5 Hz), 9.15 (0.5H, d, J = 8.0 Hz ), 9.17 (0.5H, d, J = 8.0 Hz), 9.60 (0.5H, s), 10.11 (0.5H, s); MS (ES +) m / e 284 [MHJ +, 282 [MHJ +. b) 3-Fenñ-5- (pmdin-2-ümethoxy) -l, 2,3a, 4,7-pentaazaddopenta-fa] naphthalene -0,25 Hydrate and 3-Fenfl-5- (pyridin-2-ñmethoxy) -l, 2,3a, 4,8-pentaazacidopenta [glnaphthalene • 0.5 Hydrate Sodium hydride (76 mg of a 60% dispersion in oil, 1.9 mmol) was added to a solution of 2-pyridine carbinol (180 ml, 1.9 mmol) in dry DMF (10 ml) at room temperature under nitrogen. After 45 minutes, the mixture of doroimidates from Step a) (380 mg, 1.35 mol) was added. After an additional hour at room temperature, the reaction mixture was diluted with water (200 ml) and extracted with dichloromethane (400 ml and 2 × 200 ml). The combined extracts were washed with brine (100 ml), dried (MgSO), filtered and evaporated. The residue was recrystallized from methanol, propordinating a mixture of phthalazines (136 mg) as a 1: 1 mixture - which could not be separated by convendonal chromatography. The two isomers were separated by preparative HPLC using a Pirkle-type column of 3,5-dinitrobenzoin phenol gum, providing: first eluted: -3-Fenñ-5- (pyridin-2-ylmethoxy) -l, 2,3a, 4 , 7-pentaazacidopenta [a] -naphthalene • 0.25 Hydrate: mp > 190 ° C; ? NMR (360 MHz, CDCI3) d 5.79 (2H, s), 7.34-7.37 (HH, m), 7.52-7.58 (3H, m), 7.61 (HH, d) , J = 7.9 Hz), 7.83 (ΔI, t, J = 7.7 Hz), 8.34 (2H, d, J = 8.9 Hz), 8.47 (ΔI, d, J = 7.8 Hz), 8.90 (HH, d, J = 4.0 Hz), 9.11 (HH, d, J = 5.3 Hz), 9.61 (HH, s); (Regio-chemistry was determined using nOe data). MS (ES +) m / e 355 [MH] +. Calculated AnáHsis C, 67.00; H, 3.87; N, 23.37. C2oHi4N60. 0.25 H2O requires C, 66.93; H, 4.07; N, 23.42%. and then eluted: - 3-Fenu-5- (pyridin-2-ylmethoxy) -l, 2,3a, 4,8-? entaazacidopenta [c.J-naphthalene • 0.5 Hydrate: p.f. > 170 ° C; ? NMR (360 MHz, CDCl 3) d 5.75 (2H, s), 7.33-7.37 (HH, m), 7.50-7.60 (4H, m), 7.82 (HH, t , J = 7.8 Hz), 8.07 (HH, d, J = 5.3 Hz), 8.29-8.33 (2H, m), 8.68-8.70 (HH, m) , 9.05 (1H, d, J = 5.3 Hz), 10.03 (1H, s); (the regiochemistry was determined using nOe data). MS (ES +) m / e 355 [MH] +. Analysis calculated C, 66.25; H, 3.89; N, 22.73. C20H14 6O. 0.5 H2O requires C, 66.11; H, 4.16; N, 23.13%.

EXAMPLE 12 (±) -8-Methyl-3-phenyI-6-, 2-pyridyl) methyloxy-7,8,9,10-tetrahydro-1,2,4-triazoIor3,4-alftalazine a) Ethyl 4-metfl-2 - ('trifluoromethanesulfon-hydroxy) cidohex-l-enecarboxflate N, N-diisopropyethylamine (52 ml, 0.3 mol) was added to a 4-methyl-2-dhehexanone-l-carboxylate solution of ethyl (50 g, 0.27 mol) in dichloromethane (500 ml) at -10 ° C, followed by addition of dropwise trifluoromethane sulfonium (57 ml, 0.3 mol) drop, maintaining the temperature between -5 and -10 ° C. The reaction mixture was allowed to warm to room temperature and was stirred for 3 hours. TLC showed 80% reaction, it was allowed to cool to -5 ° C and more N, N-diisopropynethylamine (14 ml, 0.1 mole) was added, followed by trifluoromethanesulfon chloride (15.5 ml, , 1 mol) and the reaction mixture was stirred for 15 hours at room temperature. The mixture was washed with cold water (2 x 200 ml), cold saturated sodium bicarbonate (2 x 200 ml) and brine (1 x 200 ml). The organic layer was dried (MgSO 4), filtered and evaporated to afford the desired product (85g) as a colorless oil. ? NMR (250 MHz, CDClg) d 1.04 (3H, d, J = 6.5 Hz), 1.43 (3H, m), 1.73-2.09 (4H, m), 2.39- 2.63 (3H, m), 4.25 (2H, m). b) 2-Metfl 4-methex-l-ene-1, 2-dicarboxylic acid 1-ethyl Palladium (II) acetate (1.85 g, 0.0083 mol), bis (diphenphosphine) ferro-ceno ( 9 g, 0.0162 mol), methanol (250 ml) and triethyl amine (75.5 ml, 0.54 mol) were added to a solution of the product of Example 12, Step a (85 g, 0.27 mol) in DMF ( 500 ml) at -20 ° C. Gaseous carbon monoxide was passed through the solution for 15 minutes and then the reaction was heated to 60 ° C and kept in a carbon monoxide atmosphere for 15 hours. The solution was allowed to cool and the solvent was removed at high vacuum. The residue was dissolved in ethyl acetate, then washed with water (4 x 200 ml) and brine (1 x 200 ml). The organic layer was dried (MgSO 4), filtered and evaporated, yielding the crude product of the title that was purified by chromatography on silica gel using 0-10% ethyl acetate in hexane, propranning the desired product (27 g) as a yellow oil. ? NMR (250 MHz, CDCk) d 1.12 (3H, d, J = 6.5 Hz), 1.33 (3H, m), 1.70-1.96 (4H, m), 2.35- 2.61 (3H, m), 3.73 (3H, s) 4.25 (2H, m). c) 4-Metddohex-l-ene-1, 2-dicarboxylic acid A solution of potassium hydroxide (32.7 g, 0.6 mol) in water (20 ml) was added to a solution of the product of Example 12, Step b (33 g, 0.15 mol) in ethanol (200 ml) and heated to reflux for 15 hours. The solution was allowed to cool, the solvent was removed at high vacuum, water (200 ml) was added and then concentrated hydrochloric acid until pH 2. The aqueous layer was extracted with dichloromethane (5 x 200 ml), the combined organic layers were washed. with brine (1 x 200 ml), dried (MgS?), filtered and evaporated, yielding the desired product as a yellow oil (16.7 g). * H NMR (250 MHz, DMSO) d 1.15 (3H, d, J = 6.5 Hz), 1.21 (1H, m), 1.86 (3H, m), 2.37 (3H, m), 3.34 (2H, broad s). d) 4-Metfl- (3,4,5,6-tetrahydro) phthalic anhydride The product of Example 12 Step c (16.5 g, 0.89 mol) in acetic anhydride (200 ml) was refluxed for 15 hours . The acetic anhydride was removed at high ford, the residue was dissolved in toluene and then evaporated, yielding the desired product as an oil (15.2 g). ? NMR (250 MHz, DMSO) d 1.03 (3H,?, J = 6.5 Hz), 1.24 (1H, m), 1.96 (3H, m), 2.23 (3H, m) . e) 6-Methan-5,6,7,8-tetrahydrophthalazine-1,4-dione This compound was prepared using the procedures described in Example 1, Step a) using 4-methanic anhydride (3,4,5, 6-tetramethyl) phthale instead of bicido acid anhydride [2.2.2] od-2-ene-2,3-dicarboxy HCO. Data for the title compound: * H NMR (250 MHz, DMSO) d 1.13 (3 H, d, J = 6.8 Hz), 1.19 (H, m), 1.76 (3 H, m), 2.29 (H, m), 2, 50 (2H, m), 11.2 (2H, broad s); MS (ES +) m / e 181 [MH] +. f) 1, 4-Didoo-6-metfl-5,6,7,8-tetrahydrophthalazine This compound was prepared using the procedures described in Example 1, Step b) using 6-methü-5,6,7,8- tetrahydroftalazine-l, 4-dione instead of 4,5-diazatricide [6.2.2.2.7jdodec-2 (7) -eno-3,6-dione. Data for the title compound:? NMR (250 MHz, CDOb) d 1.29 (3H, d, J = 7.0 Hz), 1.90 (4H, m), 2.54 (1H, m), 2.93 (1H, m) , 3.18 (H, m); MS (ES +) m / e 217 + 219 [MH] +. g) (±) -6-Chloro-8-methyl-3-fem-7,8,9,10-tetrahydro-l, 2,4-triazolor-3,4-a-phthalazine and (±) -6-chloro-9- Metfl-3-phene-7,8,9,10-tetrahydro-l, 2,4-triazolo [3,4-a] phthalazine This compound was prepared using the procedures described in Example 1, Step c) using l, 4-Dior-6-methyl-5,6,7,8-tetrahydrophthalazine instead of 3,6-DOROR-4,5-diazatricide [6.2.2.2.7] dodeca-2 (7), 3,5-triene . The reaction afforded a mixture of the title compounds in a ratio of about 1: 1. The compounds were not separated at this stage. Data for the mixture of the title compounds:? NMR (250 MHz, CDCk) d 1.12 (3H, m), 1.44 (1H, m), 2.21 (2H, m), 2.77 (3H, m), 3.40 (1H, m), 7.74 (3H, m), 8.43 (2H, m); MS (ES +) m / e 299 + 301 [MH] +. h) (+) - 8-Metu-3-phenyl-6- (2-pyridine) metfloxy-7,8,9,10-tetrahydro-l, 2,4-triazolo [3,4-a-phthalazine This compound was prepared using the procedures described in Example 1, Step d) using the mixture of Example 12, Step g) in place of 3-phenyl-6- (2-? iridn) methyloxy-7,8,9,10-tetrahydro- ( 7,10-ethane) -l, 2,4-triazolo [3,4-ajftalazine. The two products were separated using chromatography on Yes gel, 0-8% methanol in dichloromethane. The larger Rf product was recrystallized from ethyl acetate / dichloromethane to provide the title compound.

Title ? NMR (250 MHz, DMSO) d 1.23 (3 H, d, J = 6.3 Hz), 2.05 (2 H, m), 2.35 (H, m), 3.00 (2H, m), 3.24 (HH, m), 5.71 (2H, s), 7.58 (5H, m), 8.08 (HH, m), 8.36 (2H, m) 8.80 (1H, m); p.f. 185-187 ° C; MS (ES-) m / e 372 [MH] +. The minor Rf product was also isolated and showed to be (±) -9-metñ-3-phene-6- (2-pyridu) methyloxy-7,8,9,10-tetrahydro-l, 2,4-triazolo [ 3,4-a] phthalazine. The data for this compound are for the trifluoroacetate salt; ? NMR (250 MHz, DMSO) d 1.13 (3H, d, J = 6.5 Hz), 1.24 (HH, m), 1.96 (2H, m), 2.80 (3H, m) , 3.16 (HH, m), 5.60 (2H, s), 7.70 (5H, m), 8.08 (HH, d, J = 7.8 Hz), 8.20 (2H, m), 8.65 (1H, m); mp 152-154 ° C; MS (ES +) m / e 372 [MHJ +. The structure was checked by COSÍ and NOE experiments.

EXAMPLE 13 3-Phenyl-6- (2-pyridyl) methyloxy- (7,8-pentane) -l, 2t4-triazoIof4,3-blpiridazine This compound was prepared using the procedures described in Example 1, Steps a), b), c) and d) using l-cidoheptene-1,2-dicarboxylic anhydride (Proc. Indian Acad. Sci., Sect. A, 1978, 87A (10), 371) in place of bicyclo [2.2.2] od-2-ene-2,3-dicarboxylic acid anhydride in Step a). Data for the title compound: p.f. = 208 ° C. aH NMR (360 MHz, CDCk) d 1.71 (2H, m), 1.81 (2H, m), 1.99 (2H, m), 3.01 (2H, m), 3.38 (2H , m), 5.58 (2H, s), 7.28 (HH, m), 7.48 (4H, m), 7.76 (HH, m), 8.37 (2H, d, J = 7.8 Hz), 8.67 (1H, m); MS (ES +) m / e 372 [MH] +. Analysis calculated C, 70.52; H, 5.25; N, 18.44. C22H2? NsO, 0, l H 0 requires C, 70.80; H, 5.72; N, 18.76%.

EXAMPLE 14 8,8-Dimethyl-3-phenH-6- (2-pyridyl) methyloxy-7,8,9,10-tetrahydro-l, 2,4-triazoIor3,4-alftalazine a) 4,4- (Dimeth) ddohexene-1, dimethyl dimicarboxylate This compound was prepared in 62% yield by a procedure similar to that described in Example 12, Step a), but using 2-carbomethoxy-4, 4-dimethyl-acetyxanone (Liu, H.-J; Browne, EN C; Chew, S. L, Can. J. Chem., 1988, 66, 2345-2347). ? NMR (360 MHz, CDCls) d 0.96 (6H, s), 1.42 (2H, t, J = 6.4 Hz), 2.12 (2H, t, J = 2.6 Hz), 2 , 38 (2H, m), 3.76 (3H, s), 3.76 (3H, s); MS (ES +) m / e 249 [M + Na] +, 227 [M + H] +, 195 [M-OMe] +. b) 4,4- (dúnetü) cyclohexene-1,2-dicarboxylic acid A mixture of the product of Example 14, Step a) (3.78 g, 16.7 mmol) and hydroxide was heated at 80 ° C for 23 hours. potassium (3.50 g, 66.9 mmol) in ethanol (23 ml) and water (28 ml). After cooling, the mixture was concentrated to approximately 15 ml, introduced into a Dowex 50WX8-200 ion exchange column and eluted with 0-20% MeOH / H ?O, yielding 2.73 g (82%) of the desired product as a brown baby. ? NMR (250 MHz, d6-DMSO) d 1.09 (9H, s), 1.61 (2H, t, J = 6.2 Hz), 2.26 (2H, t, J = 2.8 Hz) 2.48 (2H, m). c) 4,4-fdimetfl) cidohexene-1,2-dicarboxylic anhydride This compound was prepared in 93% yield by a procedure similar to that described in Example 12, Step d), but using the product of Example 14, Step c) ? NMR (250 MHz, d6-DMSO) d 0.96 (6H, s), 1.48 (2H, t, J = 6.2 Hz), 2.13 (2H, t, J = 2.8 Hz) 2.35 (2H, m). d) 6,6-Dimetfl-5,6,7,8-tetrahydrophthalazine-l, 4-dione This compound was prepared in a yield of 92% by a procedure similar to that described in Example 1, Step a), but using the product of Example 14, Step c).

? NMR (250 MHz, d6-DMSO) d 0.92 (6H, s), 1.43 (2H, t, J = 6.4 Hz), 2.16 (2H, s), 2.38 (2H, t, J = 6.4 Hz); MS (ES) m / e 195 [M + H] +. e) 1,4-Dichloro-5,6,7,8-tetrahydro-6,6-dirnethyl-phthalazine This compound was prepared in 99% yield by a procedure similar to that described in Example 1, Step b), but using the product of Example 14, Step d). ? NMR (360 MHz, CDOb) 1.04 (6H, s), 1.65 (2H, t, J = 6.6 Hz), 2.53 (2H, s), 2.78 (2H, t, J = 6.6 and 1.3 Hz); MS (ES) m / e 235/233/231 [M + H] +. f) 6-Aoro-7,8,9,10-tetrahydro-8,8-dimethy-3-phenyl-2,4-triazolo [3,4-alftalazine] It was heated to reflux for 3 days with a trap Dean-Stark a mixture of the product of Example 14, Step e) (2.53 g, 10.9 mmol), triethylamine (1.83 mL, 13.1 mmol) and benzoic hydrazide (1.79 g, 13.1 mmol). mmol) in xylene (50 ml). The solvent was stripped and the dichloromethane (50 ml) was added to the residue. The mixture was stirreda white solid was filtered and the filtrate was evaporated in vacuo. The residue was purified by flash chromatography (silica gel, 10-20% EtOAc / CH2Cl2), yielding 2.18 g (64%) of a partially separated mixture of the 9,9-dimethyl isomer and the desired product. * H NMR (250 MHz, CDCl 3) d 1.10 (6H, s), 1.72 (2H, t, J = 6.5 Hz), 2.56 (2H, m), 3.26 (2H, m), 7.51-7.60 (3H, m), 8.42-8.47 (2H, m); MS (ES) m / e 315/313 [M + H] +. g) 8,8-Dimethy-3-phenyl-6- (2-? Mdn) methoxy-7,8,9,10-tetrahydro-l, 2,4-triazolof3,4-aJphtalazine To a stirred mixture of sodium hydride (dispersion in 60% oil, 40.4 mg, 1.01 mmol) in anhydrous DMF (5 ml), under nitrogen, was added 2-pyriducarbinol (95 ml, 0.985 mmol) and the mixture was stirred at room temperature for 1 hour. This was added by cannula to a stirred mixture of the product of Example 14, Step f) (0.205 g, 0.655 mmol) in anhydrous DMF (5 ml) and the mixture was stirred for another 28 hours, adding more sodium hydride (8, 4 and 7.6 mg) after 18 and 25 h. The mixture was partitioned between EtOAc (50 ml) and water (50 ml) and the aqueous layer was extracted again with EtOAc (2 x 50 ml). The combined organic extracts were dried (Na? -? Oi) and evaporated in vacuo. The residue was purified by flash chromatography (silica gel, 2% MeOH / CH2Cl then alumina, 80% EtOAc / CH2Cl2), affording 71.4 mg (28%) of the desired product; p.f. 133-136 ° C (CH? Ck-EtOAc-hexane); ? NMR (360 MHz, d6-DMSO) 1.10 (6H, s), 1.71 (2H, t, J = 6.5 Hz), 2.53 (2H, m), 3.20 (2H, m ), 5.59 (2H, s), 7.31 (HH, m), 7.47-7.54 (4H, m), 7.80 (HH, dd, J = 7.8 and 1.7 Hz), 8.37 (2H, dd, J = 8.0 and 1.3 Hz), 8.67 (1H, m); MS (ES) m / e 386 [M + H] +. Calculated Analysis C, 71.41; H, 6.12; N, 17.99. C23H23N5O requires C, 71.67; H, 6.01; N, 18.17%.

EXAMPLE 15 3-Phenyl-7- (piperidin-1-yl) -6- (pyridin-2-umethoxy) -l, 2,4-triazoloyl-4,3-blpiridazine • 0.45 Hydrate a) 4-Bromo-1,2-dihydropyridazine-3,6-dione A mixture of bromomaleic anhydride (50 g, 283 mmol) and sodium acetate (76.5 g, 562 mmol) in 40% acetic acid was treated. water (750 ml) with hydrazine monohydrate (16.5 ml, 339 mmol) at room temperature under nitrogen. The brown solution was stirred and heated at 100 ° C for 18 hours. After cooling, the mixture was poured into water (11) and extracted with ethyl acetate (6 x 500 ml). The combined extracts were dried (MgSO 4), filtered and evaporated to give the title compound (20 g, 37%) as an orange solid. ? NMR (250 MHz, d6-DMSO) d 7.68 (lH, broad s). MS (ES +) m / e 193 [MH] +, 191 [MH] +. This material was used without further purification. b) 4-Bromo-3,6-dithoropyridazine A solution of 4-bromo-1,2-dihydropyridazine-3,6-dione (10 g, 52 mmol) in phosphorus oxychloride (100 ml) was stirred and heated to 100 ° C under nitrogen for 16 hours. After cooling, excess phosphorus oxidide was emitted. The residue was azeotropically distilled with toluene (x2), then suspended in dichloromethane / water. The mixture was carefully basified with sodium bicarbonate (solid). It was necessary to blend the mixture adidonally to obtain two clear layers. The two layers were separated and the aqueous layer was extracted with dichloromethane (x3). The combined extracts were dried (Na2SQ?), Filtered and evaporated. The residue was purified by chromatography on silica gel, eluting with dichloromethane, propounding the title compound (5.0 g, 42%) as a colorless solid. H NMR (250 MHz, CDCk) d 7.68 (1H, broad s). MS (ES +) m / e 230 [MH] +, 228 [MH] +. c) 3,6-Didoo-4-.piperidin-l-ü) pyridazine Piperidine (475 mL, 4.8 mmol) was added to a stirred solution / suspension of 4-bromo-3,6-dithoropyridazine (1.0 g, 4.4 mmol) and potassium carbonate (1.2 g, 8.7 mmol) in dry DMF (40 ml) at room temperature under nitrogen. The mixture was stirred at room temperature for 16 hours, and then at 60 ° C for 3 hours. The reaction was poured into water (250 ml). The aqueous layer was extracted with ethyl acetate (x3). The combined organic extracts were dried (MgS?), Filtered and evaporated. The residue was purified by chromatography on silica gel, eluting with 0.5% methanol / dichloromethane, affording the title compound (1.0 g, 98%) as a colorless oil. ? NMR (250 MHz, CDCl 3) d 1.63-1.81 (6H, m), 3.24-3.29 (4H, m), 6.84 (1H, s). MS (ES +) m / e 234 [MH] +, 232 [MH] +. d) 6-Qoro-3-ferdl-7- (pi? eridin-1-ü) -l, 2,4-triazolo [4,3-b-pyridazine A mixture of 3,6-didoro-4- (piperidin) was stirred -l-ñ) pyridazine (0.55 g, 2.4 mmol), benzoic hydrazine (370 mg, 2.7 mmol), triethynamine (375 mL, 2.7 mmol) and p-acid toluenesulfonic monohydrate (510 mg, 2.7 mmol) in xylene (isomer mixture, 10 ml) and heated to reflux under nitrogen for 24 hours. After cooling, the xylene was removed in vacuo and the residue was partitioned between dichloromethane and water. The aqueous layer was extracted again with dichloromethane (x3). The combined extracts were dried (Na-tSO *), filtered and evaporated. The residue was purified by chromatography on a silica gel, eluting with 30% ethyl acetate / dichloromethane, yielding the undesired (less polar) regioisomer (177 mg, 23%) and the title compound (383 mg, 50%). (more polar). Data for the title compound:? NMR (250 MHz, CDCk) d 1.62-1.86 (6H, m), 3.09-3.13 (4H, m), 7.42 (HH, s), 7.50-7.60 (3H, m), 8.40-8.44 (2H, m). e) 3-Phen-7- (piperidin-1-ü) -6 - (? iridin-2-ümethoxy) -l, 2,4-triazol-4,3-b-pyridazine. 0.45 Hydrate Sodium hydride (60% dispersion in oil, 39 mg, 0.96 mmol) was added to a solution of 2-pyridine carbinol (104 mg, 0.96 mmol) in dry DMF (10 mL) at room temperature. environment under nitrogen. After 1 hour at room temperature, a solution of 6-doro-3-phene-7- (piperidin-1-yl) -l, 2,4-triazolo [4.3-] was added by means of a syringe. bPyridazine (200 mg, 0.64 mmol) in dry DMF (10 mL). The mixture was stirred at room temperature for 16 hours. The DMF was then emitted, and the residue was partitioned between dichloromethane and water. The aqueous layer was extracted again with dichloromethane (2x100 ml). The combined extracts were dried (Na2S?), Filtered and evaporated. The residue (248 mg) was purified by crystallization from ethyl acetate / hexane (x2) to provide the title compound (130 mg, 53%). ? NMR (250 MHz, CDCl 3) d 1.64-1.86 (6H, m), 3.20-3.26 (4H, m), 5.63 (2H, broad s), 7.22-7, 32 (2H, m), 7.42-7.56 (4H, m), 7.76 (1H, td, J = 7.7, 1.6 Hz), 8.31-8.35 (2H, m), 8.66 (ÍH, s wide). (Regiochemistry was determined using nOe data). MS (ES +) m / e 387 [MH] +. Analisys calculated C, 66.97; H, 5.85; N, 21.30. C22H22N6O. 0.45 HzO requires C, 67.08; H, 5.63; N, 20.96%.

EXAMPLE 16 3-Phenyl-7- (pyridin-4-yl) -6- (pyridin-2-ylmet-H) -l < 2,4-triazolo [4,3-blpiridazine • 0.5 Hydrate a) 3,6-Dichloro-4- (pyridin-4-ü) pyridazine A mixture of 4-bromo-1,2-dihydropyridazine-3,6-dione was deoxygenated by three acid "evacuation / nitrogen filling" (see Example 15, Step a) (530 mg, 2.8 mmol) and 4-pyridue boronic acid, di-HTH salt (500 mg, 3.7 mmol) and sodium carbonate (800 mg, 7.6 mmol) in 1,2-dimethoxyethane (20 ml). Then tetrakis (triphenphosphine) was added diode (0) (350 mg, 0.3 mmol) and the reaction mixture was deoxygenated again with three more "evacuated / filled with nitrogen" dots. The mixture was then refluxed and heated under nitrogen and protected from light for 16 hours. After cooling, volatile contents were eliminated. The residue was used without adidonal purification. The previous solid was suspended in phosphorus oxychloride (10 ml). The dark suspension was heated to reflux for 20 hours. After cooling, the volatiles were removed at once. The residue was destained azeotropically with toluene (x2), then partitioned between dichloromethane and water. The mixture was carefully basified with sodium hydrogencarbonate. The two layers were separated (a precipitate formed which can be separated by filtration through CeH-te®). The aqueous layer was extracted again with dichloromethane (x3). The combined extracts were dried (M S? 4), filtered and evaporated. The residue was purified by chromatography on silica gel, eluting with 3% methanol / dichloromethane, propounding the title compound (240 mg, 38% in the two steps) in the form of yellow sodium. aH NMR (250 MHz, dß-DMSO) d 7.77-7.79 (2H, m), 8.37 (1H, s), 8.90-8.93 (2H, m). MS (ES +) m / e 226 [MH] +, 228 [MH] +. b) 6-Chloro-3-fenfl-7- (pyridin-4-y) -l, 2,4-triazolo [4,3-b-pyridazine] A mixture of 3,6-dimer-4- (β-din) was stirred. 4-ü)? Iridazine (390 mg, 1.7 mmol), benzoin hydrazine (260 mg, 1.9 mmol), triethyl amine (270 mL, 1.9 mmol) and p-toluenesulfonic acid (32 mg., 0.2 mmol) in xylene (isomer mixture) (5 ml) and heated under nitrogen for 20 hours. The mixture was partitioned between dichloromethane and saturated aqueous potassium carbonate. The aqueous layer was extracted again with dichloromethane (x3). The combined extracts were dried (sodium sulfate), filtered and evaporated. The residue was purified by chromatography on silica gel eluting with 3% methanol / dichloromethane, propranning the title compound (218 mg, 42%) as a pale yellow solid. * H NMR (360 MHz, d6-DMSO) d 7.60-7.69 (5H, m), 8.36-8.38 (2H, m), 8.72 (H, s), 8.78 -8.80 (2H, m). MS (ES +) m / e 308 [MH] +, 310 [MH] +. c) 3-Fertfl-7 - (? iridin-4-ü) -6 - (? iridin-2-ymetoxy) -l, 2,4-triazolo [4,3-b-pyridazine. 0.5 Hydrate 2-? Iridicarbinol (105 ml, 1.1 mmol) was added to a stirred suspension of sodium hydride (60% dispersion in oil, 40 mg, 1.0 mmol) in dry DMF (10 ml) at room temperature under nitrogen. After 1 hour, a solution of 6-chloro-3-phene-7- (pyridin-4-ü) -l, 2,4-triazolo [4,3-b] ir iridazine (200 mg, 0, 65 mmol) in dry DMF (10 + 5 ml). The solution was stirred at room temperature for 16 hours and then poured into water * (100 ml). The aqueous layer was extracted with ethyl acetate (5 x 100 ml). The combined extracts were dried (Na 2 SO), filtered and evaporated The residue was triturated with ethyl acetate (20 ml) at room temperature The remaining solution (170 mg) was recrystallized from hot ethyl acetate to provide the compound of the title (120 mg, 49%) as a colorless solid, mp = 215 ° C, decomposition. NMR (360 MHz, dß-DMSO) d 5.76 (2H, s), 7.47-7.50 ( ÍH, m), 7.67-7.72 (4H, m), 7.97-8.02 (3H, m), 8.38-8.42 (2H, m), 8.72-8, 78 (2H, m), 8.87-8.89 (2H, m) MS (ES +) 381 [MH] +, Analysis calculated C, 68.21; H, 4.10; N, 21.34. C22H16N6O • 0.5 H20 requires C, 67.86; H, 4.40; N, 21.58%.

EXAMPLES 17 and 18 3-Phenyl-5-pyridin-2-ylmethoxy) -6,7,8,9-tetrahydro-l, 2 a < 4,8-pentaazar-cyclopentaphanaphthalene - 0 ^ 35 Hydrate and 3-phenyl-5- (pyridin-2-ylmethoxy) -6,7,8,9-tetrahydro-l, 2,3a, 4,7-pentaaza-cyclopentallnaphthalene • 0.75 Hydrate a) 3-Fenñ-5- (pyridin-2-ylmethoxy) -6,7,8,9-tetrahydro-l, 2,3a, 4,8-pentaazacidopenta [aJ-naphthalene and 3-Fenü-5- (pyridin -2-γ-methoxy) -6,7,8,9-tetrahydro-l, 2,3a, 4,7-pentaazadclo-penta [a] naphthalene It was subjected to hydrogenation on platinum oxide (140 mg) at 2.06 x 105 Pa for 45 minutes a mixture of 3-phene-5 - (? Iridin-2-ymetoxy) -l, 2,3a, 4,7-? Entaaza-cidopenta [a] naphthalene and 3-phene-5- (pyridine -2-ylmethoxy) -l, 2,3a, 4,8-pentaazacido? Enta [aJ-naphthalene (see Examples 10 and 11) and 2N HCl (1.0 ml, 2 mmol) in methanol (140 ml) a room temperature. The catalyst was removed by filtration through CeHte®, washing with methanol. The filtrate was evaporated and the residue was purified by chromatography on silica gel eluting with dichloromethane / methanol / ammonia - 80: 8: 1 affording the title amines (465 mg, 65%) as a yellow solid. The mixture could not be separated by flash chromatography. The two isomers were separated using the protocol described in Steps b), c) and d) below. b) Ferric-butyl ester of the acid 3-phene-5- (p dm-2-flmethoxy) -6,9-dihydro-7 // - l, 2,3a, 4,8-pentaazacidopenta [-.] naphthalene- 8-carboxylic acid and 3-phene-5- (pyridin-2-ylmethoxy) -8,9-dihydro-6g-1, 2,3a, 4,7-pentaaza-cidopenta [-.] Naphthalene tert-butyl ester -7-carboxylic acid Di-tert-butyl dicarbonate (700 mg, 3.2 mmol) was added to a stirred solution of a mixture of 3-phene-5- (pyridin-2-ylmethoxy) -6,7,8, 9-tetrahydro-l, 2,3a, 4,8-pentaazacidopenta [o-Naphthalene and 3-phene-5- (pyridin-2-y-methoxy) -6,7,8,9-tetrahydro-l, 2,3a, 4, 7-pentaazadclopenta [a] naphthalene (555 mg, 1.55 mmol) and triethyl amine (550 ml, 3.9 mmol) and 4-dimethyaminopyridine (20 mg, 0.16 mmol) in dry dichloromethane at 0 ° C under nitrogen. The The reaction was allowed to come to room temperature for 1 hour and then stirred at this temperature for 16 hours. The mixture was partitioned between dichloromethane and saturated aqueous sodium bicarbonate. The aqueous layer was extracted again with dichloromethane (x2). The combined extracts were dried (Na2S?), Filtered and evaporated. The residue was purified by chromatography on silica gel, eluting with 5% methanol / dichloromethane, propounding the title compounds as a mixture (610 mg, 86%) as a colorless solid. The two compounds could be separated by medium-pressure liquid chromatography over silica, eluting with ethyl acetate to provide: less polar: 3-phenyl-5- (pyridin-2-ylm: ethoxy) -6 acid / 3-butyl ester, 9-dihydro-7/1-l, 2,3a, 4,8-pentaazacycloetha [l] naphthalene-8-carboxyHc (274 mg). A sample was recrystallized from ethyl acetate / hexane: m.p. = 170-173 ° C. ? NMR (250 MHz, CDCl 3) d 1.52 (9H, s), 2.84-2.90 (2H, m), 3.81 (2H, t, J = 5.8 Hz), 5.00 ( 2H, broad s), 5.60 (2H, s), 7.32 (ÍH, dd, J = 7.5, 4.9 Hz), 7.49-7.55 (4H, m), 7, 79 (1H, td, J = 7.7, 1.8 Hz), 8.34-8.38 (2H, m), 8.64-8.69 (1H, m). MS (ES +) m / e 459 [MH] +. AnáHsis calculated C, 61.83; H, 5.60; N, 17.52. C25H26N6O3. 1.4 H2O requires C, 62.07; H, 6.00; N, 17.37%. less polar: 3-phenyl-5 - (? iridin-2-methoxy) -8,9-dihydro-6i? -l, 2,3a, 4,7-? entaazacyclopenta [-.] naphthalene acid ester. -7-carboxylic acid (227 mg). A sample was recrystallized from ethyl acetate / hexane: m.p. = 166-168 ° C. ? NMR (250 MHz, CDCl 3) d 1.53 (9H, s), 3.20-3.26 (2H, m), 3.82 (2H, t, J = 5.8 Hz), 4.62 ( 2H, broad s), 5.61 (2H, s), 7.31 (ÍH, dd, J = 7.0, 5.5 Hz), 7.48-7.56 (4H, m), 7, 79 (1H, td, J = 7.7, 1.7 Hz), 8.35-8.38 (2H, m), 8.64-8.68 (1H, m). MS (ES +) m / e 459 [MHJ +. Analysis calculated C, 65.76; H, 5.81; N, 18.25. C 25 H 26 N 6 O 3 requires C, 65.49; H, 5.71; N, 18.32%. c) 3-Ferdl-5- (p-din-2-ümethoxy) -6,7,8,9-tetrahydro-l, 2,3a, 4,8-pentaazaddopentafúJnaphthalene • 0,35 Hydrate Trifluoroacetic acid (3 ml) was added ) to a c-butyl ester / e solution of 3-Phenu-5 - (? Mdin-2-urea) -6,9-dihydro-77-1, 2,3a, 4,8-pentaazaddopenta [n.] naphthaleno-8-carboxylic acid (255 mg, 0.56 mmol) in dry dichloromethane (3 ml) at 0 ° C under nitrogen. After 1 hour, the volatiles were removed in vacuo and the residue was partitioned between dichloromethane and saturated aqueous sodium carbonate. The aqueous layer was extracted again with didoromethane (x2) The combined extracts were dried (Na 2 S 4), filtered and evaporated. The residue was purified by chromatography on silica gel, eluting with didorometa-no / methanol / ammonia (60: 8: 1 -> 50: 8: 1) to give the title amine (176 mg, 88%) as a colorless soap, pf = 175-178 ° C. ? NMR (360 MHz, d6-DMSO) d 2.62-2.66 (2H, m), 3.08 (2H, t, J = 5.7 Hz), 4.13 (2H, s), 5 6 (2H, s), 7.37 (IH, dd, J = 6.9, 5.3 Hz), 7.50-7.59 (4H, m), 7.87 (ÍH, td, J = 7.7, 1.7), 8.22-8.25 (2H, m), 8, 62-8.64 (ÍH, m). MS (ES +) m / e 359 [MHJ +.

Analysis calculated C, 66.14; H, 4.98; N, 22.71. ? oHisN? 0 • 0.35 H20 requires C, 65.86; H, 5.17; N, 23.04%. d) 3-Fenu-5- (pmdin-2-iknetoxi) -6,7,8,9-tetr.ahidro-l, 2,3a, 4,7-pentaazaridopentaf 1-naphthalene -0,75 Hydrate was added trifluoroacetic acid (3 ml) to a solution of tert-butyl ester of 3-phenyl-5- (pyridin-2-γ-netoxy) -8,9-dihydro-6-l, 2,3a, 4,7-? entaazacyclopenta [-I] -naphthalene-7-carboxyHco (217 mg, 0.47 mmol) in dry dichloromethane (3 ml) at 0 ° C under nitrogen. After 1 hour, the volatiles were removed under vacuum and the residue was partitioned between dichloromethane and saturated potassium carbonate. The aqueous layer was extracted again with dichloromethane (x2). The combined extracts were dried (Na 2 S 4), filtered and evaporated. The residue was purified by chromatography on silica gel, eluting with dichloromethane / methanol / ammonia (60: 8: 1) propordinating the title amine (162 mg, 96%) as a colorless solid, m.p. = 157-159 ° C. ? NMR (360 MHz, d6-DMSO) d 2.92-2.96 (2H, m), 3.07 (2H, t, J = 5.8 Hz), 3.84 (2H, s), 5, 56 (2H, s), 7.36 (ΔH, dd, J = 6.7, 4.9 Hz), 7.52-7.60 (4H, m), 7.87 (ΔH, td, J = 7.8, 1.7), 8.23 (2H, dd, J = 6.3, 1.9 Hz), 8.62-8.64 (1H, m). MS (ES +) m / e 359 [MH] +. Analysis calculated C, 64.93; H, .31; N, 22.30. C? OHisN? 0, 0.75 HzO requires C, 64.59; H, 5.29; N, 22.60%.

EXAMPLE 19 7-Methyl-3-phenyl-5- (pyridin-2-ylmethoxy) -6,7,8,9-tetrahydro-l, 2,3a, 4,7-pentaazacyclopentaphnaphthalene Sodium cyanoborohydride (55 mg, 0.88 mmol) was added to a stirred solution of 3-phene-5 - (? Mdin-2-methoxy) -6,7,8,9-tetiahydro-l, 2,3a, 4 , 7-pentaazadclopenta [a] naphthalene (126 mg, 0.35 mmol) and acetic acid (100 mL, 1.75 mmol) in dry methanol (10 mL) at room temperature under nitrogen. The mixture was cooled to 0 ° C and aqueous formaldehyde (35 ml, 0.48 mmol) was added. The reaction was stirred at 0 ° C for 30 minutes, and then at room temperature for 15 hours. The reaction was quenched with saturated aqueous potassium carbonate (5 ml). The volatiles were removed by ford, and then the residue was partitioned between dichloromethane and water. The aqueous layer was extracted again with dichloromethane (x3). The combined extracts were dried (Na2S?), Filtered and evaporated. The residue was purified by chromatography on silica gel, eluting with dichloromethane / methanol / ammonia (95: 5: 0.5? 92: 7: 1), affording the title amine (130 mg, 100%) as a colorless solid. . This material was recrystallized from ethoxy acetate: m.p. 186-188 ° C. ? NMR (360 MHz, CDCl 3) d 2.57 (3H, s), 2.84 (2H, t, J = 5.7 Hz), 3.27-3.31 (2H, m), 3.61 ( 2H, broad s), 5.59 (2H, s), 7.28 (ÍH, dd, J = 6.7, 4.9 Hz), 7.45-7.52 (4H, m), 7, 75 (ΔH, td, J = 7.8, 1.8 Hz), 8.35 (2H, dd, J = 8.3, 1.8 Hz), 8.64-8.68 (ΔI, m) . MS (ES +) m / e 373 [MH] +. Analysis calculated C, 67.95; H, 5.57; N, 22.43. C2iH2oN60 requires C, 67.73; H, 5.41; N, 22.57%.

EXAMPLE 20 3-Phenyl-6-pyridin-2-ylmethoxy) -7-Cytofen-2-yl) -l, 2,4-triazolof4,3-blpiridazine 0.45 Hydrate This compound was prepared using the procedures described in Example 16, Steps a), b) and c) except that 2-thiophene boronic acid was used in place of 4- iodide boronic acid, di-Ht. Salt in Step a) and 1.1 equivalents of p-toluenesulfonic acid in Stage b) instead of 0.1 equivalents. Data for the title compound:? NMR (250 MHz, CDCl 3) d 5.74 (2H, s), 7.18 (1H, dd, J = 5.2, 3.8 Hz), 7.28-7.34 (1H, m), 7.50-7.58 (5H, m), 7.71-7.77 (2H, m), 8.28 (IH, s), 8.38-8.42 (2H, m), 8, 68-8.72 (IN, m). MS (ES +) m / e 386 [MH] +. Analysis calculated C, 64.46; H, 4.16; N, 17.63. C21H15N5OS. 0.45 HzO. 0.05 (C4H10O) requires C, 64.10; H, 3.82; N, 17.35%.

EXAMPLE 21 3-Phenyl-6- (pyridin-2-ylmethoxy) -7-phthiophen-3-? I) -l, 2,4-triazolof4,3-b | pyridazine 0.2 Hydrate This compound was prepared using the procedures described in Example 16, Steps a), b) and c) except that 3-thiophene boronic acid was used in place of 4-pyridin boronic acid, di-Hthium salt, in Step a) and 1.1 equivalents of p-toluenesulfonic acid in Step b) instead of 0.1 equivalents. Data for the title compound:? NMR (250 MHz, CDCl 3) d 5.70 (2H, s), 7.26-7.32 (HH, m), 7.44-7.58 (6H, m), 7.70-7.80 (HH, m), 7.96 (HH, broad s), 8 , 20 (ÍH, s), 8.40- 8.43 (2H, m), 8.58 (ÍH, broad d, J = 5.6 Hz). MS (ES +) m / e 386 [MHJ +. Calculated analysis C, 64.83; H, 4.11; N, 17.78. C21H15N5OS. 0.2 HzO. 0.07 (QH10O) requires C, 65.04; H, 3.69; N, 17.38%.

EXAMPLE 22 (-fc) -3-Phenyl-6- (2-pyridiQn? Eti-Oxi-7,8,9,10-tetrahydro- (7,10-propane) -l, 2,4-triazolof3,4-alftalazipa This compound was prepared using the procedures described in Example 1, Steps a), b), c) and d), using bidclo [3.2.2] non-6-ene-6,7-dicarboxyH anhydride (.

Chem. Soc, 2524, 1970) in place of bicido anhydride [2.2.2Jod-2-ene-2,3-dicarboxylic in the Stage a). Data for the title compound: p.f. = 187 ° C. ? NMR (360 MHz, CDCb) d 1.42-2.19 (10H, m), 3.56 (HH, s), 3.98 (HH, s), 5.60 (2H, s), 7, 28 (ÍH, m), 7.48 (4H, m), 7.74 (ÍH, m), 8.38 (2H, d, J = 7.8 Hz), 8.66 (1H, m); MS (ES +) m / e 398 [MHJ +. Analysis calculated C, 72.93; H, 5.85; N, 17.64. C 24 H 23 N 5 O requires C, 72.52; H, 5.83; N, 17.62%.

EXAMPLE 23 3-f4-Methyl) phenyI-6- (2-pyridyl) methyloxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolof3,4-a1phta-Iazine This compound was prepared using the procedures described in Example 1, Steps a), b), c) and d), using 4-toluic hydrazide in place of benzoin hydrazine in Step c). Data for the title compound: p.f. = 167 ° C. * H NMR (360 MHz, DMSO) d 1.40 (4H, m), 1.90 (4H,), 2.40 (3H, s), 3.48 (H, s), 3.74 (OH) , s), 5.57 (2H, s), 7.36 (3H, m), 7.57 (HH, d, J = 7.8 Hz), 7.87 (HH, ddd, J = 7, 8, 7.8 &1.7 Hz), 8.14 (2H, d, J = 8.2 Hz), 8.68 (1H, m); MS (ES +) m / e 398 [MH] +. Analysis calculated C, 72.37; H, 5.73; N, 17.62. C 24 H 23 N 5 O requires C, 72.52; H, 5.83; N, 17.62%.

EXAMPLE 24 3- (3-Methoxy) phenyl-6- (2-pyridyl) methyloxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazole-3,4-alftalazine This compound was prepared using the procedures described in Example 1, Steps a), b), c) and d) using 3-methoxybenzohydrazide in place of benzoyl hydrazine in Step c). Data for the title compound: p.f. = 185 ° C. 1 H NMR (360 MHz, DMSO) d 1.40 (4H, m), 1.91 (4H, m), 3.49 (HH, s), 3.76 (HH, s), 3.85 (3H , s), 5.59 (2H, s), 7.08 (HH, m), 7.37 (HH, m), 7.47 (HH, t, J = 8.0 Hz), 7.59 (HH, d, J = 7.9 Hz), 7.88 (2H, m), 7.96 (HH, m), 8.64 (HH, m); MS (ES +) m / e 414 [MH] +. Analisys calculated C, 69.36; H, 5.65; N, 16.58. C24H23N5O2 requires C, 69.72; H, 5.61; N, 16.94%.

EXAMPLE 25 3- (2-Fluoro) phenyl-6- (2-pyridyl) methyloxy-7,8,9,10-tetrabidro- (7,10-ethane) -l, 2,4-triazolor-3,4-alftalazine This compound was prepared using the procedures described in Example 1, Steps a), b), c) and d) using 2-fluorobenzohydrazide in place of benzoin hydrazine in Step c). Data for the title compound: p.f. = 159 ° C. ? NMR (360 MHz, CDCl 3) d 1.51 (4H, m), 1.92 (4H, m), 3.56 (HH, s), 3.98 (HH, s), 5.46 (2H, s), 7.26 (3H, m), 7.44 (IH, d, J = 7.8 Hz), 7.54 (IH, m), 7.71 (IH, m), 7.80 ( ÍH, m), 8.63 (ÍH, m); MS (ES +) m / e 402 [MHJ +. Calculated Analysis C, 68.81; H, 4.81; N, 17.17. C23H20FN5O requires C, 68.81; H, 5.02; N, 17.45%.

EXAMPLE 26 3-f3-Pyridyl) -6- (2-pyridyl) methyloxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolor-3,4-alftalazine This compound was prepared using the procedures described in Example 1, Steps a), b), c) and d), using nicotinic acid hydrazide in place of benzoin hydrazine in Step c). Data for the title compound: p.f. = 198 ° C. ? NMR (360 MHz, CDCl 3) d 1.49 (4H, m), 1.96 (4H, m), 3.59 (HH, s), 3.99 (HH, s), 5.61 (2H, s), 7.28 (HH,), 7.49 (2H, m), 7.78 (HH, m), 8.72 (3H, m), 9.69 (HH, s); MS (ES +) m / e 385 [MH] +. Analisys calculated C, 67.56; H, 5.66; N, 19.51. C 22 H 20 N 6 O requires C, 67.27; H, 5.65; N, 19.61%.

EXAMPLE 27 3-Cyclopropyl-6- (2-pyridyl) - netyloxy-7,8,9,10-tetrahydro-f7.10-ethane) -l, 2,4-triazolof3,4-alfta-Iazine This compound was prepared using the procedures described in Example 1, Steps a), b), c) and d), using hydrazide of the ddopropanecarboxylic acid in place of benzoy hydrazine in Step c). Data for the title compound: p.f. = 160 ° C. ? NMR (360 MHz, CDCls) d 1.09 (2H, m), 1.31 (2H, m), 1.44 (4H, m), 1.89 (4H, m), 2.38 (1H, m), 3.52 (HH, s), 3.90 (HH, s), 5.57 (2H, s), 7.28 (HH, m), 7.52 (HH, d, J = 7 , 9 Hz), 7.76 (HH, m), 8.64 (HH, m); MS (ES +) m / e 348 [MH] +. Analisys calculated C, 69.12; H, 5.85; N, 20.19. C20H21N5O requires C, 69.14; H, 6.09; N, 20.16%.

EXAMPLE 28 6-6-Methyl) -2-pyridinmethyloxy-3-phenyl-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolof3,4-alftalazine hydrochloride This compound was prepared using the procedures described in Example 1, Steps a), b), c) and d), using 6-methy-2-hydroxymethyrimidine in place of 2-pyriducarbinol in Step d). An additional step at the end of the synthesis was to dissolve the compound in a solution of hydrogen doudole in methanol before evaporating and recrystallizing. Data for the title compound: p.f. = 255 ° C. ? NMR (360 MHz, DMSO) d 1.42 (4H, m), 1.91 (4H, m), 2.71 (3H, s), 3.51 (H, s), 3.78 (H, s), 5.80 (2H, s), 7.59 (4H,), 7.80 (HH, d, J = 7.8 Hz), 8.22 (HH, m), 8.30 (2H) , d, J = 7.9 Hz); MS (ES +) m / e 398 [MH] +. Analisys calculated C, 61.67; H, 5.36; N, 14.74. C24H23N5O.HCl requires C, 61.28; H, 5.36; N, 14.89%.

EXAMPLE 29 6 - ((3-Metii) -2-pyridyl) methyloxy-3-phepyl-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazoloI3.4-alftalazine This compound was prepared using the procedures described in Example 1, Steps a), b), c) and d), using 3-methy-2-hydroxymethyrimidine in place of 2-pyriducarbinol in Step d). Data for the title compound: p.f. = 245 ° C. ? NMR (360 MHz, CDCls) d 1.48 (4H, m), 1.88 (4H, m), 2.43 (3H, s), 3.47 (1H, s), 3.98 (1H, s), 5.63 (2H, s), 7.26 (HH, m), 7.49 (3H, m), 7.60 (HH, d, J = 7.5 Hz), 8.43 ( 2H, d, J = 7.8 Hz), 8.48 (ΔI, d, J = 7.1 Hz); MS (ES +) m / e 398 [MHJ-. Calculated Analysis C, 72.09; H, 5.76; N, 17.79. C 24 H 23 N 5 O • 0, lH 2 O requires C, 72.20; H, 5.86; N, 17.54%.

EXAMPLE 30 6-f (4-Metin-2-pyridyl) methyloxy-3-phenyl-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazol-3,4-a-1-phthalazine This compound was prepared using the procedures described in Example 1, Steps a), b), c) and d), using 4-methan-2-hydroxymethyridine in place of 2-pyriduchenbinol in Step d). Data for the title compound: p.f. = 190 ° C. ? NMR (360 MHz, CDCb) d 1.49 (4H,), 1.93 (4H, m), 2.39 (3H, s), 3.58 (H, s), 3.99 (H, s) ), 5.59 (2H, s), 7.13 (HH, d, J = 7.3 Hz), 7.35 (HH, s), 7.50 (3H, m), 8.41 (2H) , d, J = 7.8 Hz), 8.51 (ÍH, d, J = 7.3 Hz); MS (ES +) m / e 398 [MH] +. Analisys calculated C, 72.91; H, 5.78; N, 17.32. C 24 H 23 N 5 O requires C, 72.52; H, 5.83; N, 17.62%.

EXAMPLE 31 6-f (5-Methyl) -2-pyridyl) methyloxy-3-phenyI-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolor-3,4-alpha-azazine This compound was prepared using the procedures described in Example 1, steps a), b), c) and d), using 5-methy-2-hydroxymethyl pyridine in place of 2-pyriducarbinol in Step d). Data for the title compound: p.f. = 205 ° C. ? NMR (360 MHz, CDCfe) d 1.48 (4H, m), 1.92 (4H, m), 2.38 (3H, s), 3.56 (H, s), 3.99 (H, s), 5.58 (5H, s), 8.45 (3H, m); MS (ES +) m / e 398 [MH] +. Analysis calculated C, 72.66; H, 5.72; N, 17.32. C 24 H 23 N 5 O requires C, 72.52; H, 5.83; N, 17.62%.

EXAMPLE 32 3-Phenit-6- (3-pyridyl) methyloxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolor-3,4-alftala-ina This compound was prepared using the procedures described in the example 1, steps a), b), c) and d), using 3-? Iriducarbinol in place of 2-pyriducarbinol in Step d). Data for the title compound: p.f. = 202 ° C. ? NMR (360 MHz, DMSO) d 1.39 (4H, m), 1.90 (4H, m), 3.40 (HH, s), 3.74 (HH, s), 5.58 (2H, s), 7.46 (HH, m), 7.56 (3H, m), 7.97 (HH, d, J = 7.8 Hz), 8.36 (2H, d, J = 7.9 Hz), 8.58 (HH, m), 8.77 (HH, m); MS (ES +) m / e 384 [MH] +. Calculated Analysis C, 72.70; H, 5.49; N, 18.19. C24H2? N50 requires C, 72.04; H, 5.52; N, 18.26%.

EXAMPLE 33 3-Phenyl-6- (4-pyridyl) methyloxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolof 3,4-alftalazine This compound was prepared using the procedures described in the example 1, steps a), b), c) and d), using 4-pyridincarbinol instead of 2-? Iriducarbinol in Step d). Data for the title compound: p.f. = 205 ° C. ? NMR (360 MHz, CDCl 3) d 1.49 (4H, m), 1.95 (4H, m), 3.55 (HH, s), 3.99 (HH, s), 5.49 (2H, s), 7.41 (2H, d, J = 6.0 Hz), 7.49 (3H, m), 8.32 (2H, d, J = 7.8 Hz), 8.69 (2H, d, J = 6.0 Hz); MS (ES +) m / e 384 [MH] +. Analysis calculated C, 71.29; H, 5.16; N, 17.82. C 24 H 21 N 5 O • 0, lH 2 O requires C, 71.70; H, 5.54; N, 18.18%.

EXAMPLE 34 3-Phenyl-6- (2-fl-methyl) imidazoyl) methyloxy-7,8,9,10-tetrahydro-7,10-ethane) -l, 2,4-triazolof 3,4-alftalazine This compound was prepared using the procedures described in Example 1, steps a), b), c) and d), using l-metfl-2-hydroxymethimidazole in place of 2-pyridinecarbinol in Step d). Data for the title compound: p.f. = 274 ° C. ? NMR (360 MHz, CD3OD) d 1.52 (4H, m), 2.03 (4H, m), 3.50 (HH, s), 3.82 (3H, s), 3.88 (HH, s), 5.64 (2H, s), 7.05 (HH, s), 7.23 (HH, s), 7.66 (3H, m), 8.41 (2H, d, J = 7 8 Hz); MS (ES +) m / e 387 [MH] +. Analysis calculated C, 68.20; H, 5.69; N, 21.77. C22H22 6O requires C, 68.38; H, 5.74; N, 21.75%.

EXAMPLE 35 6-f3-Cyanophenyl) methyloxy-3-phenyl-7,8,9,10-tetrabidro- (7,10-ethane) -l, 2,4-triazolor-3,4-alftalazine a) 6-Hydroxy-3-phene-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolor-3,4-alftalazine The product of example 1, Step c) was dissolved (3.0 g, 9.6 mmol) in 10% aqueous 1,4-dioxane (100 ml) with sodium hydroxide solution (24 ml of 2 N, 5 eq molar) and the reaction mixture was heated to reflux for 3 days. The organic solvent was removed by rotary evaporation and the residue was partitioned between water (250 ml) and diethyl ether (250 ml). The organic layer was separated and washed twice with diethyl ether (100 ml), then treated with 5 N hydrochloric acid until a pH of 2 was attained. The solids which precipitated in the solution were collected by filtration and subjected to the desired product. (2.7 g, mp ~ 300 ° C, decomposition). ? NMR (250 MHz, CDCl 3) d 1.35 (4H, m), 2.00 (4H, m), 3.49 (1H, s), 3.84 (1H, s), 7.71 (3H, m), 8.54 (2H, d, J = 7.8 Hz); MS (ES +) m / e 293 [MH] +. Analysis calculated C, 69.33; H, 5.32; N, 19.17. C? 7H? 5N 0 requires C, 69.86; H, 5.19; N, 19.23%. b) 6- (3-Cyanophen) methoxy-3-phene-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolor-3,4-a-phthalazine The product of the example was dissolved 35, Step a) (0.3 g, 1.02 mmol) in dimethylformamide (40 ml) with 60% sodium hydride (0.049 g, 1.2 eq mol) and heated at 80 ° C for 20 minutes. minutes Next, α-bromo-weta-toluomtrüo (0.22 g, 1.1 eq mol) was added, and heating was continued for 14 hours. Water was added until the solution became turbid and the whey which prepopulated was then collected by filtrate and purified by chromatography on silica gel using 0-30% ethyl acetate in dichloromethane as eluent. The product was recrystallized from ethyl acetate / hexane to provide the desired compound (0.22 g). Data for the title compound: p.f. = 216 ° C. ? NMR (360 MHz, CDCl 3) d 1.48 (4H, m), 1.93 (4H, m), 3.54 (HH, s), 3.98 (HH, s), 5.80 (2H, s), 7.42 (HH, d, J = 3.2 Hz), 7.50 (3H, m), 7.86 (HH, d, J = 3.2 Hz), 8.45 (2H, d, J = 7.8 Hz); MS (ES +) m / e 408 [MHJ +. Calculated Analysis C, 64.54; H, 4.98; N, 17.79. C21H19N5OS requires C, 64.76; H, 4.92; N, 17.98%.

EXAMPLE 36 6- (1- (3,5-Dimethyl) pyrazolyl) methyloxy-3-phenyl-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazole-3,4- a.phtalazine This compound was prepared using the procedures described in example 1, steps a), b), c) and d), using l-hydroxymethyl-3,5-dimethyl-urazole in place of 2-pyriducarbinol in Step d). Data for the title compound: p.f. = 210 ° C. ? NMR (360 MHz, CDCl 3) d 1.43 (4H, m), 1.89 (4H, m), 2.27 (3H, s), 2.32 (3H, s), 3.41 (1H, s), 3.96 (HH, s), 5.96 (HH, s), 6.27 (2H, s), 7.54 (3H, m), 8.51 (2H, d, J = 7 , 8Hz); MS (ES +) m / e 401 [MH] +. Analisys calculated C, 69.32; H, 6.07; N, 21.01. C 23 H 24 N 6 O requires C, 68.98; H, 6.04; N, 20.99%.

EXAMPLE 37 6- (4-f2-Methyl) thiazolyl) methyloxy-3-phenyI-7,8,9,10-tetrahydro-r7,10-ethane) -1 ^ 2,4-triazolor-3,4-alftalazine This compound was prepared using the procedure described in Example 35, Step b), using 4-chloromethane-2-methanediazole instead of a-bromo- / we / a-toluonitrou. Data for the title compound: p.f. = 180 ° C. ? NMR (360 MHz, CDCl 3) d 1.47 (4H, m), 1.91 (4H, m), 2.76 (3H, s), 3.53 (1H, s), 4.00 (1H, s), 5.55 (2H, s), 7.26 (1H, s), 7.52 (3H, m), 8.48 (2H, d, J = 7.8 Hz); MS (ES +) m / e 404 [MHJ +. Analysis calculated C, 65.82; H, 5.17; N, 17.25. C24H21N5OS requires C, 65.49; H, 5.25; N, 17.36%.

EXAMPLE 38 3-Phenyl-6- (2-quinoxalipyl) methyloxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazoIof3.4-alftalazine This compound was prepared using the procedure described in Example 35, Step b), using 2-chloromethinquinoxaline in place of a-bromo-> 2α-ta-toluonitrile. Data for the title compound: p.f. = 250 ° C. ? NMR (360 MHz, DMSO) d 1.43 (4H, m), 1.92 (4H, m), 3.54 (H, s), 3.75 (H, s), 5.88 (2H, s), 7.44 (3H, m), 7.89 (2H, m), 8.13 (4H, m), 9.18 (1H, s); MS (ES +) m / e 435 [MH] +. Analisys calculated C, 71.15; H, 5.10; N, 18.66. C2 H22N6O • 0.375 HzO requires C, 70.77; H, 5.20; N, 19.05%.

EXAMPLE 39 3-Phenit-6- (3-pyridazinyl) methyloxy-7,8,9,10-tetrahydro-7,10-ethane) -l, 2,4-triazolof 3,4-alfta-Iazine This compound was prepared using the procedure described in Example 35, Step b), using 3-doromethypyridazine (prepared by the procedure of Jeronim et al., Chem. Ber., 1987, 120, 649-651) instead of a-bromo-we / a-toluonitrüo. The 3- Doromethylpyridazine is a particularly unstable reagent and polymerizes rapidly upon heating, whereby the reaction was carried out immediately after forming the alkylating agent. Data for the title compound: p.f. = 215 ° C. 1 H NMR (360 MHz, CDCl 3) d 1.49 (4H, m), 1.91 (4H, m), 3.54 (HH, s), 4.01 (HH, s), 5.85 (2H, s), 7.54 (4H , m), 7.71 (ÍH, dd, J = 8.5 and 1.7 Hz), 8.36 (2H, d, J = 7.8 Hz), 9.22 (1H, dd, J = 4.9 and 1.7 Hz); MS (ES +) m / e 385 [MHJ +.

Analysis calculated C, 68.60; H, 5.31; N, 21.65. C 22 H 20 N 6 O requires C, 68.73; H, 5.24; N, 21.86%.

EXAMPLE 40 6-fl-Bepcyl-2-imidazolipmethyloxy-3-phenyl-7,8,9,10-tetrahydro-7,10-ethane) -l, 2,4-triazoIof3,4-alftalazine This compound was prepared using the procedures described in example 1, steps a), b), c) and d), using l-benzin-2- (hydroxymethyl) -imidazole (prepared according to the procedure of Birker, Godefroi, Helder and Reedijk , J. Am. Chem. Soc, 1982, 104, 7556) in place of 2-pyriducarbinol in Step d). Data for the title compound: p.f. = 205 ° C. 1 H NMR (360 MHz, CDCfe) d 1.20 (2H, m), 1.43 (2H, m), 1.80 (4H,), 3.11 (ΔH, t, J = 2.8 Hz) , 3.92 (HH, t, J = 2.7 Hz), 5.24 (2H, s), 5.55 (2H, s), 7.03 (3H, m), 7.18 (HH, d, J = 1.2 Hz), 7.28 (3H, m), 7.50 (3H, m), 8.43 (2H, m); MS (ES +) m / e 463 [MH] +. Anahsis found C, 71.49; H, 5.62; N, 17.82. C28H26N6? - 0.5H O requires C, 71.32; H, 5.77; N, 17.82%.

EXAMPLE 41 3-Phenyl-6- (isoquiP? Lin-l-yl) methyloxy-7,8,9,10-tetrahydro-7,10-etao) -l, 2,4-triazolo [3,4-alftalazine This compound was prepared using the procedure described in Example 35, Step b), using 1-doromethalisoquinoline in place of a-bromo- / weta-toluonitriu. Data for the title compound: p.f. = 230 ° C. ? NMR (360 MHz, CDCl 3) d 1.45 (4H, m), 1.88 (4H, m), 3.45 (HH, s), 3.97 (HH, s), 6.09 (2H, s), 7.43 (3H, m), 7.71 (3H, m), 7.93 (HH) , d, J = 8.2 Hz), 8.24 (HH, d, J = 8.4 Hz), 8.42 (2H, m), 8.58 (HH, d, J = 6.2 Hz ); MS (ES +) m / e 434 [MH] +. Calculated Analysis C, 75.04; H, 5.25; N, 16.40. C27H23N5O requires C, 74.81; H, 5.35; N, 16.16%.

EXAMPLE 42 6- (l-Ethyl-2-yl idazolyl) methyloxy-3-phenyl-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolor-3,4-alftalazine This compound was prepared using the procedures described in example 1, steps a), b), c) and d), using l-etii-2- (hydroxymethyl) imidazole (prepared according to the procedure of Tasaka, Teranishi, Matsushita, Tamura, Hayashi, Okanogi and Itoh, Chem. Pharm. Bull., 1994, 42, 85) in place of 2-? Iriducarbinol in Step d). Data for the title compound: p.f. = 254 ° C. i H NMR (500 MHz, DMSO) d 1.34 (3 H, t, J = 7.2 Hz), 1.36 (4 H, m), 1.87 (4 H, m), 3.28 (H, s) ), 3.74 (HH, s), 5.58 (2H, q, J = 7.2 Hz), 5.55 (2H, s), 6.96 (HH, s), 7.33 (HH) , s), 7.58 (3H, m), 8.50 (2H, m); MS (ES +) m / e 401 [MHJ +. Analysis found C, 68.98; H, 6.07; N, 20.74. C 23 H 24 N 6 O requires C, 68.98; H, 6.04; N, 20.99%.

EXAMPLE 43 3-FepiI-6- (l-pyrazolIiI) methyloxy-7,8,9,10-tetrahydro- (7,10-etapo) -l, 2,4-triazolof3,4-alftalazine This compound was prepared using the procedures described in example 1, steps a), b), c) and d), using l- (hydroxymethyl) pyrazole (prepared according to the procedure of Julia, Martinez-Martorell and Elguero, Heteroyicles, 1986, 24, 2233) in place of 2-pyriducarbinol in Step d). In the final stage, it was necessary to add the product of Step c) at the same time as sodium hydride, in order to provide the right product. Data for the title compound: p.f. = 196 ° C. ? NMR (360 MHz, DMSO) d 1.47 (4H, m), 1.99 (4H, m), 3.38 (HH, s), 3.87 (HH, s), 6.51 (HH, m), 6.62 (2H, s), 7.73 (4H, m), 8.18 (HH) , m), 8.60 (2H, m); MS (ES +) m / e 373 [MHJ +. Analysis found C, 67.73; H, 5.42; N, 22.48. C2? H2oN60 requires C, 67.73; H, 5.41; N, 22.57%.

EXAMPLE 44 3-Phenyl-6- (N-pyrroidinikarbonyl) methyloxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolof 3,4-alftalazipa a) N-ChloromethanecarbonhydrinHdine Triethylamine (11.8 ml, 0.084 mole) was added, followed by the addition, dropwise, of chloroacetyl chloride (6.2 ml, 0.077 mole) in dichloromethane (20 ml) to a piperazide solution. -rohodin (5 g, 0.07 mol) in dichloromethane (100 ml) at 0 ° C stirred for 2 hours and allowed to warm to room temperature. The reaction was washed with water (2x100 ml), brine (1x100 ml), the organic layers were dried (MgSOc), filtered and evaporated to provide the required product (9.8 g) which was used without further purification. b) 3-Phen-6- (N-pyrroHydrocarbon) methyloxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-alftalazine This compound was prepared using the procedure described in Example 35, Step b), using N-dorometücarbonüpirroHdina in place of a-bromo-metho-toluonitrile. Data for the title compound: p.f. = 219-221 ° C. ? NMR (360 MHz, DMSO) d 1.38 (4H, m), 1.77 (2H, m), 1.95 (6H, s), 3.30 (2H, m), 3.39 (1H, s), 3.44 (2H, m), 3.75 (1H, s), 5.11 (2H, s), 7.53 (3H, m), 8.29 (2H, m); MS (ES +) m / e 404 [MHJ +. Analysis calculated C, 68.12; H, 6.23; N, 17.03. C 23 H 25 N 5 O 2 requires C, 68.47; H, 6.24; N, 17.36%. 7? EXAMPLE 45 6- (4- (3-Methyl) pyridyl> methyloxy-3-phenyl-7.8,9.10-tetrahydro-7,10-ethane) -l ^, 4-triazolor-3,4-alftalazine This compound was prepared using the procedures described in example 1, steps a), b), c) and d), using 4-hydroxymethyl-3-methypyridine in place of 2-pyriducarbinol in Step d). Data for the title compound: p.f. = 226 ° C. ? NMR (360 MHz, CDCl 3) d 1.48 (4H, m), 1.93 (4H, m), 2.40 (3H, s), 3.54 (H, s), 4.00 (1H, s), 5.49 (2H, s), 7.39 (ΔH, d, J = 5.0 Hz), 7.45 (3H, m), 8.31 (2H, m), 8.47 ( 2H, d, J = 7.8Hz); MS (ES +) m / e 399 [MH] +. Calculated Analysis C, 71.50; H, 6.11; N, 16.50. C 24 H 23 N 5 O requires C, 71.16; H, 6.00; N, 16.87%.

EXAMPLE 46 3-Fepi-6- (2-quinolinipmethyloxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] -phthalazine This compound was prepared using the procedure described in Example 35 Step b), using 2-chloromethylquinoline in place of -bromo- »? -. To-toluonitriu. Data for the title compound: p.f. = 203 ° C. ? NMR (360 MHz, CDCl 3) d 1.51 (4H, m), 1.95 (4H, m), 3.61 (HH, s), 4.00 (HH, s), 5.80 (2H, s), 7.44 (3H, m), 7.53 (2H, m), 7.82 (2H, m), 8.30 (4H, m); MS (ES +) m / e 434 [MH] +. Analisys calculated C, 74.92; H, 5.38; N, 15.96. C27H23N5O requires C, 74.81; H, 5.35; N, 16.16%.

EXAMPLE 47 6- (2-Imidazolyl) methyloxy-3-phenyl-7,8,9,10-tetrahydro-7,10-etaP?) -1,2,4-triazolo [3,4-alftalazine hydrochloride] a) 2- (Hydroxymethyl) -l - [[2- (trimethylsilyl) ethoxy] methimidazole Sodium borohydride (0.42 g) was added at 0 ° C with stirring to 1 - [[2- (trimethylsilyl) ethoxy] methyl] -l / 1-imidazole-2-carboxaldehyde (prepared according to the procedure of Whitten, Matthews and McCarthy, J. Org. Chem., 1986, 51, 1891) (7.45 g) in methanol (30 ml). The solution was stirred at 0 ° C for 40 minutes. Saturated sodium doride solution (15 ml) was added and the mixture was stirred at room temperature for 15 minutes. The methanol was removed in vacuo and the resulting aqueous solution was washed with ethyl acetate (3 x 50 ml). The organic layers were combined, dried (sodium sulfate) and concentrated in vacuo, and an oil was extracted, which crystallized at 0 ° C. The solid was washed and recrystallized from hexane, yielding l - [[2- (trimethylsily) ethoxy] methyl] -2- (hydroxymethyl) imidazole as colorless crystals (1.99 g). ? NMR (250 MHz, CDCk) d 0.00 (9H, s), 0.93 (2H, t, J = 8.2 Hz), 3.54 (2H, t, J = 8.2 Hz), 4 , 73 (2H, s), 4.77 (2H, broad s), 5.39 (2H, s), 6.94 (HH, d, J = 1.4 Hz), 7.00 (HH, d , J = 1.4 Hz); MS (ES +) m / e 229 [MHJ +. b) 6- (2-Imidazole) methyloxy-3-phene-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a-phthalazine hydrochloride] This compound was prepared using the procedures described in the example 1, steps a), b), c) and d), using l - [[2- (trimetüsñü) ethoxyJmetü] -2- (hydroxymethyl) imidazole in place of 2-pyriducarbinol in Step d). An additional step was to take the product from Step d) and stir it at 50 ° C in 5N hydrochloric acid for 90 minutes before evaporating and recrystallizing from ethyl acetate / methanol. Data for the title compound: p.f. = 219 ° C (decomposition). ? NMR (360 MHz, DMSO) d 1.42 (4H, m), 1.91 (4H, m), 3.51 (HH, s), 3.78 (HH, s), 5.84 (2H, s), 7.59 (3H, m), 7.76 (2H, s), 8.23 (2H, m); MS (ES +) m / e 373 [MH] +. Anal found C, 55.07; H, 5.11; N, 18.22. C21H20N6O. 2HC1. 0.7H2O requires C, 55.08; H, 5.15; N, 18.35%.

EXAMPLE 48 3-Phenyl-6- (2-thiazolyl) methyloxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazole-3,4-alftalazine This compound was prepared using the procedures described in example 1, steps a), b), c) and d), using 2-hydroxymeththiazole in place of 2- ir id id id id ir ir ir ir ir ir ir ir ir ir ir ir ir ir ir ir. Data for the title compound: p.f. = 183 ° C. ? NMR (360 MHz, CDCl 3) d 1.48 (4H, m), 1.92 (4H, m), 3.51 (H, s), 3.99 (H, s), 5.49 (2H, s), 7.52 (4H, m), 7.69 (2H, m), 7.81 (1H, m), 8.35 (2H, d, J = 7.8 Hz); MS (ES +) m / e 390 [MHJ +. Analysis calculated C, 73.93; H, 5.17; N, 17.37. C? SH? INsO requires C, 73.68; H, 5.19; N, 17.19%.

EXAMPLE 49 6-r 2 -f 5-Methyl) thiazom) methyloxy-3-phetyi-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolor-3,4-alftalazine This compound was prepared using the procedures described in example 1, steps a), b), c) and d) using 2-hydroxymeth-5-methythiazole in place of 2-pyriducarbinol in Step d). Data for the title compound: p.f. = 228 ° C. ? NMR (360 MHz, CDCl 3) d 1.47 (4H, m), 1.93 (4H,), 2.50 (3H, s), 3.53 (1H, s), 3.99 (1H, s) ), 5.74 (2H, s), 6.95 (1H, s), 7.51 (3H, m), 8.45 (2H, d, J = 7.8 Hz); MS (ES +) m / e 404 [MHJ-. Calculated Analysis C, 65.92; H, 5.30; N, 17.21. C22H21N5OS requires C, 65.49; H, 5.25; N, 17.36%.

EXAMPLE 50 6- (2- (4-Methyl) thiazolyl) methyloxy-3-phenyl-7.8,9.10-tetrahydro- (7a0-ethane) -l, 2,4-triazoloyl-3,4-alftalazine This compound was prepared using the procedures described in example 1, steps a), b), c) and d), using 2-hydroxymeth-4-methynnazole in place of 2- [beta] -hydridiccarbinol in the Stage d). Data for the title compound: p.f. = 165 ° C. ? NMR (360 MHz, CDQj) d 1.47 (4H, m), 1.92 (4H, m), 2.49 (3H, s), 3.52 (ÍH, s), 3.98 (H, s), 5.70 (2H, s) , 7.49 (4H, m), 8.46 (2H, d, J = 7.9 Hz); MS (ES +) m / e 404 [MH] +. Analysis calculated C, 65.92; H, 5.33; N, 17.09. C22H21N5OS requires C, 65.49; H, 5.25; N, 17.36%.

EXAMPLE 51 6- (2-3 ^ -Dimethyl) pyridyl) methyloxy-3-phepyl-7.8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolof 3,4-alftalazine This compound was prepared using the procedures described in example 1, steps a), b), c) and d), using 2-hydroxymeth-3,5-dimethy-pyridine (prepared according to the procedure of Boekelheide and Linn, J. Am. Chem. Soc, 1954, 76, 1286) in place of 2-pyridinecarbinol in Step d). Data for the title compound: p.f. = 199 ° C. * H NMR (360 MHz, CDCl 3) d 1.46 (4H, m), 1.86 (4H, m), 2.34 (3H, s), 2.38 (3H, s), 3.44 ( ÍH, s), 3.96 (HH, s), 5ß7 (2H, s), 7.39 (HH, s), 7.49 (3H, m), 8.31 (HH, s), 8, 47 (2H, d, J = 7.8 Hz); MS (ES +) m / e 412 [MHJ +. Analysis calculated C, 72.51; H, 6.12; N, 16.86. C25H25N5O • 0, lH2O requires C, 72.65; H, 6.15; N, 16.94%.

EXAMPLE 52 3-FePl-6- (2-pyrazinyl) methyloxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazoyl-3,4-alfta-Azine This compound was prepared using the procedure described in Example 35 Step b), using 2-chloromethypyrazine (prepared by the procedure of Jeronim et al., Chem. Ber., 1987, 120, 649-651) in place of a-bromo- / weta-toluonitrile. Data for the title compound: p.f. = 215 ° C. ? NMR (360 MHz, CDCk) d 1.50 (4H, m), 1.94 (4H, m), 3.57 (H, s), 4.00 (ÍH, s), 5.65 (2H, s), 7.51 (3H, m), 8.38 (2H, d, J = 7.8 Hz), 8.63 (2H, m ), 8.84 (ÍH, s); MS (ES-) m / e 385 [MH] *. Analysis calculated C, 68.53; H, 5.24; N, 21.86. C22H20N6O requires C, 68.73; H, 5.24; N, 21.86%.

EXAMPLE 53 6-f2-f4.6-Dimethyl) pyridyl) methyl-d-3-phenyl-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo 3,4 - alftalazine This compound was prepared using the procedure described in Example 1, steps a), b), c) and d), using 2-hydroxymethyl-4,6-dimethylpyridine (prepared analogously to the procedure of Boekelheide and Linn, J. Am. Chem. Soc., 1954, 76, 1286) in place of 2-pyriducarbinol in Step d). Data for the title compound: p.f. = 200 ° C. ? NMR (360 MHz, CDCla) d 1.48 (4H, m), 1.93 (4H, m), 2.34 (3H, s), 2.59 (3H, s), 3.57 (1H, s), 3.98 (HH, s), 5.55 (2H, s), 6.98 (HH, s), 7.14 (HH, s), 7.51 (3H, m), 8, 43 (2H, m); MS (ES +) m / e 412 [MH] +.

EXAMPLE 54 3-PhenyL-6- (4-thiazolyl) methyloxy-7,8,9,10-tetrahydro-7,10-ethane) -l, 2,4-triazolo [3,4-alftalazine This compound was prepared using the procedures described in the example 1, steps a), b), c) and d), using 4-hydroxymeththiazole (prepared analogously to the procedure of Boekelheide and Linn, J. Am. Chem. Soc, 1954, 76, 1286) instead of 2-? iridcarcarol in Stage d). Data for the title compound: p.f. = 219 ° C. ? NMR (360 MHz, CDCl 3) d 1.46 (4H, m), 1.89 (4H, m), 3.51 (HH, s), 3.97 (HH, s), 5.66 (2H, s), 7.52 (4H, m), 8.46 (2H, d, J = 7.8 Hz), 8.88 (1H, s); MS (ES +) m / e 390 [MH] +. Analisys calculated C, 64.71; H, 4.90; N, 17.88. C21H19N5OS requires C, 64.76; H, 4.91; N, 17.98%.

EXAMPLE 55 6- (2- (5,6-Dimethyl) pyridyl) methyloxy-3-phenH-7,8,9,10-tetrahydro-7,10-ethane) -l, 2,4-triazolof 3,4-alftalazine This compound was prepared using the procedures described in example 1, steps a), b), c) and d), using 2-hydroxymethyl-5,6-dimethyl-pyridine (prepared as described in WO 93/21158) instead of 2-pyridinecarbinol in step d). Data for the title compound: p.f. = 250 ° C. ? NMR (360 MHz, CD3OD) d 1.58 (4H, m), 2.10 (4H, m), 2.56 (3H, s), 2.84 (3H, s), 3.71 (1H, s), 3.83 (HH, s), 5.95 (2H, s), 7.75 (3H, m), 8.05 (HH, d, J = 8.06 Hz), 8.39 ( 3H, m); MS (ES +) m / e 412 [MH] +. Calculated Analysis C, 62.62; H, 5.44; N, 14.39. C25H25N50.1.9HC1 requires C, 62.46; H, 5.64; N, 14.53%.

EXAMPLE 56 6- (4-Methyl-2-imidazolium) methyloxy-3-phenH-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazoIor3,4-alftalazine hydrochloride a) 2- (Hydroxymethyl) -4-methyl-1 - [[2- (trimethoxy) ethoxymemetfl] -imidazole and 2- (hydroxymethyl) -5-methy-lf [2- (trimethoxyHl) ethoxy] -methionimidazole This mixture of The compounds were prepared analogously to l - [[2- (trimethylene) ethoxymethyl] -2- (hydroxymethyl) imidazole (see example 47, Step a). No attempt was made to separate the 4- and 5-methyl substituted isomers, since both compounds propred the desired product after removal of the working proton group. Data for l - [[2- (trimetüsüü) ethoxy] methyl] -4 (5) -metü-2- (hydroxymethyl) imidazole:? NMR (250 MHz, CDCl 3) d 0.00 (9H, s), 0.91 (2H, m), 2.18 and 2.25 (3H, 2 xs), 3.53 (2H, m), 3 , 53 (2H, m), 4.66 and 4.68 (2H, 2 xs), 5.30 and 5.33 (2H, 2 xs), 6.65 and 6.69 (1H, 2 xs); MS (ES +) m / e 243 [MH] +. b) 6- (4-Metfl-2-imidazoHl) methyloxy-3-phene-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo hydrochloride [3,4 α] phthalazine This compound was prepared using the procedure described in example 1, steps a), b), c) and d), using the products of example 56 a) in place of 2- ir ir id id id id ir ir ir ir ir ir ir ir ir ir ir ir ir ir ir. An adidonal step was to take the product from Step d) and stir at 50 ° C in 5N hydrochloric acid for 90 min before evaporating and recrystallizing from ethanol / ethyl acetate. Data for the title compound: p.f. = 220 ° C (decomposition). aH NMR (360 MHz, DMSO) d 1.43 (4H, m), 1.91 (4H, m), 2.29 (3H, s), 3.50 (H, s), 3.77 (H) , s), 5.80 (2H, s), 7.43 (1H, s), 7.59 (3H, m), 8.28 (2H, m); MS (ES +) m / e 387 [MHJ +. Analysis found C, 54.0; H, 6.0; N, 16.5. 1.8H20. 0.2 H8O2 requires C, 53.76; H, 5.78; N, 16.48%.

EXAMPLE 57 3-Phenyl-6- (4-pyrimidinipmethyloxy-7,8,9,10-tetrahydro-7,10-ethane) -l, 2,4-triazolo [3,4-alfta-Iazine This compound was prepared using the procedure described in Example 35 Step b), using 4-chloromethypyrimidine (prepared by the procedure of Jeronim et al., Chem. Ber., 1987, 120, 649-651) in place of a-bromo-thio-toluonitrile. Data for the title compound: p.f. = 194 ° C. ? NMR (360 MHz, CDCl 3) d 1.51 (4H, m), 1.96 (4H, m), 3.59 (HH, s), 4.01 (HH, s), 5.58 (2H, s), 7.49 (4H, m), 8.33 (2H, d, J = 7.8 Hz), 8.81 (HH, m), 9.26 (HH, s); MS (ES +) m / e 385 [MHJ +. Calculated Analysis C, 68.64; H, 5.29; N, 21.58. C 22 H 20 N 6 O requires C, 68.73; H, 5.24; N, 21.86%.

EXAMPLE 58 6- (4- (2-Ethyl) thiazolyl) methyloxy-3-phenyl-7,8,9,10-tetrabidro- (7.10-etaPo) -l, 2,4-triazolof3,4-a hydrochloride] phthalazine This compound was prepared using the procedure described in Example 35 Step b), using 4-doromethy-2-etiothiazole instead of a-bromo-we α-toluonitr o. Data for the title compound: p.f. = 168 ° C. ? NMR (360 MHz, CDCl 3) d 1.46 (7H, m), 1.99 (4H, m), 3.13 (2H, t, J = 7.6 Hz), 3.66 (1H, s) , 4.53 (HH, s), 5.67 (2H, s), 7.42 (HH, s), 7.62 (3H, m), 8.45 (2H, m); MS (ES +) m / e 418 [MHJ +. Analisys calculated C, 59.66; H, 5.32; N, 14.90. C23H23N5OS. HQ 0.5H2O requires C, 59.67; H, 5.44, 15.12%.

EXAMPLE 59 6- (6-Chloro-3-pyridazinipmethyloxy-3-phenyl-7,8,9,10-tetrahydro-7,10-ethane) -l, 2,4-triazolof 3,4-alftalazine This compound was prepared using the procedure described in Example 35 Step b), using 3-doromethy-6-chloro-ir-iridazine (prepared by the procedure of Jeronim et al., Chem. Ber., 1987, 120, 649-651 ) instead of a-bromo-zne / a-toluonitrüo. Data for the title compound: p.f. = 206 ° C. ? NMR (360 MHz, CDCls) d 1.51 (4H, m), 1.94 (4H, m), 3.51 (HH, s), 4.00 (HH, s), 5.81 (2H, s), 7.51 (4H, m), 7.67 (1H, d, J = 8.8 Hz), 8.34 (2H, d, J = 7.7 Hz); MS (ES +) m / e 419 [MHJ +. Calculated Analysis C, 62.95; H, 4.43; N, 19.60. C22H19CIN6O. 0, lH2O requires C, 62.81; H, 4.60; N, 19.98%.

EXAMPLE 60 6- (2-Imidazolyl) methyloxy-3- (4-methylphenyl) -7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-alftalazine hydrochloride This compound was prepared using the procedure described in Example 1, steps a), b), c) and d), using 4-toluic hydrazide in place of benzoyl hydrazine in Step c), and l - [[2- (tri ? netüsiHl) -etoxi]? netñJ-2- (Hdroxi? netil) -midazole (prepared as described in Example 47, Step a) in place of 2-pyridinecarbinol in Step d). An adidonal step was to take the product from Step d) and stir at 50 ° C in 5N hydrochloric acid for 90 minutes before evaporating and recrystallizing from ethanol / ethyl acetate. Data for the title compound: p.f. = 214 ° C (decomposition). ? NMR (360 MHz, DMSO) d 1.42 (4H, m), 1.91 (4H, m), 2.43 (3H, s), 3.51 (1H, s), 3.78 (1H, s), 5.86 (2H, s), 7.43 (2H, d, J = 8.1 Hz), 7.76 (2H, s), 8.12 (2H, d, J = 8.2) Hz); MS (ES +) m / e 387 [MH] +. Anahsis found C, 54.64; H, 5.72; N, 16.94. C22H22N6O. 2HC1. 1.5 H2O requires C, 54.33; H, 5.60; N, 17.28%.

EXAMPLE 61 6- (4-Hydroxymethylphenyl) methyloxy-3-fepYl-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazoIof3,4-alftalazine The title compound was prepared as part of a rapid analogous sequence using the following methodology. A solution of 6-doro-3-phene-7,8,9,10-tetrahydro- (7,10-ethane) -l was added to a test tube with a closed glass seal with a septum under nitrogen. 2,4-triazolo [3,4-ajftalazine (50 mg) in dimethylformamide (1.5 ml), followed by Htlium bis (trimethylsulf) amide as a 1 mol solution in hexanes (0.5 ml). The reaction was stirred at room temperature for 18 hours. TLC showed completion of the reaction and the mixture was poured into water (10 ml) and the precipitate formed by filtration was isolated.

Don and dried in a forging oven at 80 ° C, propranning the title compound (48 mg).

This was caraderized by mass pedometry and HPLC; MS (ES +) m / e 413 [MH] +, HPLC > 98% (decreases in HP1090, using a Hichrom S50DS2 column, 23 cm, flow rate of 1 ml / min.and 50% acetonitrile / phosphate buffer pH 3.5 as a mobile phase).

EXAMPLE 62 6- (4-Hydroxybutyl) oxy-3-phenyl-7,8,9,10-tetrahydro-.7,10-ethane) -l, 2,4-triazolof3,4-alftalazine This compound was prepared using the procedure described in Example 61, using 1,4-dihydroxybutane instead of 4-hydroxymethylenebenzyl alcohol. Data for the title compound: MS (ES +) m / e 365 [MH] +, HPLC > 99% (desdended in an HP1090, using a Hichrom S50DS2 column, 23 cm, flow rate of 1 ml / min and 50% acetonitrile / phosphate buffer pH 3.5 as the mobile phase).

EXAMPLE 63 6-cs! R-7 H - (4-Hydroxymethylcyclohexyl) methyloxy-3-phenyl-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo f3, 4-a] phthalazine This compound was prepared using the procedure described in Example 61, using czV / ra «s-1, 4-dihydroxymethideclohexane instead of 4-hydroxymethyl alcohol. Data for the title compound: MS (ES +) m / e 419 [MH] +, HPLC 82% and 17% (descends in an HP1090, using a Hichrom S50DS2 column, 23 cm, flow rate of 1 ml / min and acetonitrile at 50% / phosphate buffer pH 3.5 as mobile phase).

EXAMPLE 64 6- (3-Hydroxymethylphenyl) methyloxy-3-phenyl-7,8,9,10-tetrahydro- (7,10-etapo) -l, 2,4-triazolo [3,4-alftalazine This compound was prepared using the procedure described in Example 61 using 3-hydroxymethylenebenzyl alcohol in place of 4-hydroxymethylenebenzene alcohol. Data for the title compound: MS (ES +) m / e 413 [MH] +, HPLC > 99% (decreases in an HP1090, using a Hichrom S50DS2 column, 23 cm flow rate of 1 ml / min and 50% acetonitrile / phosphate buffer pH 3.5 as a mobile phase).

EXAMPLE 65 6- (l-Methyl-l, 2,4-triazol-3-yl) methyloxy-3-phenyl-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4 -triazolof3,4- alftalazine This compound was prepared using the procedures described in the example 1, steps a), b), c) and d), using (l-methyl-1'-l, 2,4-triazol-3-yl) -methanol (prepared using the conditions described in EP-A- 421210) in place of 2-pyriducarbinol in Step d). Data for the title compound: p.f. = 237 ° C. ? NMR (360 MHz, CDCk) d 1.47 (4H, m), 1.88 (4H, m), 3.51 (ÍH, s), 3.96 (4H, s), 5.54 (2H, s), 7.50 (3H, m), 8.07 (H, s), 8.52 (2H, d, J = 7 ^ Hz); MS (ES +) m / e 388 [MH] +. Analysis calculated C, 64.90; H, 5.38; N, 25.18. C 21 H 21 N 7 O requires C, 65.10; H, 5.46; N, 23.51%.

EXAMPLE 66 6-f2-MethyI-1, 2,4-triazol-3-yl) methyloxy-3-phenyI-7,8,9-tetrahydro- (7,10-ethane) -l, 2,4-triazole-3,4 - alftalazine This compound was prepared using the procedures described in the example 1, steps a), b), c) and d), using (2-metñ-2i? -l, 2,4-triazol-3-y) methanol (prepared using the conditions described in EP-A-421210 ) in place of 2-pyriducarbinol in Step d). Data for the title compound: p.f. = 270 ° C. ? NMR (360 MHz, CDCls) d 1.46 (4H, m), 1.93 (4H, m), 3.45 (HH, s), 3.96 (3H, s), 3.99 (HH, s), 5.62 (2H, s), 7.52 (3H, m), 7.94 (1H, s), 8.39 (2H, d, J = 7.8 Hz); MS (ES +) m / e 388 [MH] +. Analisys calculated C, 65.40; H, 5.47; N, 25.29. C 21 H 21 N 7 O requires C, 65.10; H, 5.46; N, 23.51%.

EXAMPLE 67 3-Pheniyl-6- (3-cyclopropyllithioxy-2-pyridyl) methyloxy-7,8,9,10-tetrahydro- (7,10-et-u? O) -l, 2,4-triazolol 3,4 -alftaIazina a) 3-Cidopropylmethyloxy-2-hydroxymethyl pyridine Potassium hydroxide (5.2 g, 0.093 mol) was added to a powder under nitrogen, added to DMSO (30 ml) and stirred for 20 min under nitrogen at room temperature. The mixture was cooled to 0 ° C and 3-hydroxy-2-hydroxymethyl pyridine hydrochloride (5.0 g, 0.031 mol) was added. The suspension was stirred at 0 ° C for 1 hour before the addition of cidopro-methyl bromide (3.01 ml, 4.2 g, 0.031 mol). The mixture was allowed to warm to room temperature and was stirred under nitrogen overnight. Water (100 ml) was added and the resulting solution was acidified to pH 1 with hydrochloric acid (5 N). The solution was washed with dichloromethane (3 x 100 ml), basified to pH 14 with sodium hydroxide solution (4 N), and washed again with dichloromethane (3 x 100 ml). The organic layers of the second extraction were combined, washed with water (1 x 100 ml) and saturated sodium chloride solution (1 x 100 ml), dried over magnesium sulfate and concentrated in vacuo to provide 3-cyclopropylmeti-oxy-2. Hydroxymethyl pyridine as a dark brown solid (2.40 g). 1 H NMR (250 MHz, CDCl 3) d 0.35 (2H, m), 0.65 (2H, m), 1.26 (1H, m), 3.85 (2H, d, J = 6.8 Hz ), 4.33 (1H, broad s), 4.77 (2H, s), 7.13 (2H, m), 8.13 (2H, m); MS (ES +) m / e 180 [MHJ-. b) 3-Phen-6- (3-ddopropflmetuoxi-2-pyridn) methyloxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-aJphtalazine This compound was prepared using the procedure described in example 1, steps a), b), c) and d), using 3-cidopropümetüoxi-2-hydroxymethyrinine instead of 2-pyriducarbinol in Step d). Data for the title compound: p.f. = 213 ° C. ? NMR (360 MHz, CDCl 3) d 0.28 (2H, m), 0.53 (2H, m), 1.17 (1H, m), 1.47 (4H, m), 1.88 (4H, m) 3.50 (HH, s), 3.88 (2H, d, J = 6.7 Hz), 3.96 (HH, s), 5.67 (2H, s), 7.26 (2H) , m), 7.47 (3H, m), 8.22 (1H, m), 8.46 (2H, d, J = 6.6 Hz); MS (ES +) m / e 454 [MH] +. Anahsis found C, 71.43; H, 5.98; N, 15.39. C27H27N5O2 requires C, 71.50; H, 6.00; N, 15.44%.

EXAMPLE 68 3-FepYl-6- (3-ethoxy-2-i) iridipmethyloxy-7,8,9,10-tetrahydro-7,10-ethane) -l, 2,4-triazoIof3,4-a1phtalazine a) 3-Ethoxy-2-hydroxymethyl pyridine This compound was prepared using the procedure described in Example 67 Step a), using iodoethane in place of cydopropylmethyl bromide. ? NMR (250 MHz, CDCl 3) d 1.44 (3H, t, = 7.0 Hz), 4.06 (2H, q, = 7.0 Hz), 4.75 (2H, s), 7.16 (2H, m), 8.14 (1H, m); MS (ES +) m / e 154 [MH] +. b) 3-Phen-6- (3-ethoxy-2-pyridine) methyloxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-ajftalazine This compound was prepared using the procedure described in Example 1, steps a), b), c) and d), using 3-ethoxy-2-hydroxymethyl pyridine in place of 2-pyridinecarbinol in the Stage d). Data for the title compound: p.f. = 230 ° C. ? NMR (360 MHz, CDCl 3) d 1.38 (3H, t, J = 7 Uz), 1.44 (4H, m), 1.88 (4H, m), 3.50 (1H, t, = 2 , 6 Hz), 3.96 (ÍH, t, = 2.6 Hz), 4.10 (2H, q, .7 = 6.9 Hz), 5.64 (2H, s), 7.26 (2H, m), 7.49 (3H, m), 8.23 (1H, m), 8.45 (2H, m); MS (ES +) m / e 428 [MH] +. Analysis found C, 70.50; H, 5.93; N, 16.41. C25H25N5O2 requires C, 70.24; H, 5.89; N, 16.38%.

EXAMPLE 69 6- (6-MetiIpyridin-2-yl) methyloxy-3-phenH-l, 2,4-triazolof3,4-alftalazine a) 2-Acetoxymeth-6-methyl-iridine Acetic anhydride (23 ml) was heated to 110 ° C and 2,6-lutidine N-oxide (20 g) was added dropwise over 1 hour. The solution was heated at 110 ° C for five hours. After cooling, the crude mixture was stripped off yielding 2-acetoxymethyl-6-methypyridine (18.4 g, p.b. 110-120 ° C @ 15 mmHg). b) 2-Hydroxymethyl-6-metfl? iridine 2-Acetoxymeth-6-methylanidine (5 g) was added to saturated hydrochloric acid in methanol (250 ml, prepared by adding 25 ml of acetyl chloride to 225 ml of methanol) . The reaction mixture was stirred at room temperature for 18 hours. The solvent was stripped and the residue was dissolved in dichloromethane (100 ml) and washed with 2N sodium hydroxide solution (3 x 50 ml). The combined organic layers were washed with brine (1 x 200 ml), then dried (MgSO 4), filtered and evaporated, yielding the desired product as an oil (2.6 g). ? NMR (250 MHz, CDCI3) d 2.54 (3H, s), 3.80 (HH, broad s), 4.72 (2H, s), 7.04 (2H, d, J = 7.7Hz) , 7.57 (ÍH, t, = 7.7 Hz). c) L-doro-4-hydrazinophthalazine hydrochloride 1,4-Dichlorophthalazine (20 g) was added to a stirred solution of hydrazine hydrate (40 ml) in ethanol (120 ml) at 80 ° C. This reaction mixture was stirred at 80 ° C for 0.5 hours, then allowed to cool and the product was collected by filtrate and dried under vacuum, donating l-chloro-4-hydrazinophthalazine hydrochloride (14.6 g). aH NMR (250 MHz, DMSO) d 4.64 (2H, s very wide), 7.2 (ÍH, s very wide), 7.92 (4H, wide m). d) 6-aoro-3-phene-1, 2,4-triazolor-3,4-a1phthalazine. Triethyl amine (7.24 ml) and benzoyl chloride (6.04 ml) were added to a solution of 1-chlorohydrochloride. 4-hydrazinophthalazine (10 g) in dioxane (220 ml). The mixture was refluxed for 8 hours under nitrogen. After cooling, the reaction mixture was concentrated in vacuo and the obtained solid was collected by filtration, washed with water and diethyl ether and dried in vacuo, by coupling the title compound (12.0 g). JH NMR (250 MHz, DMSO) d 7.60 (3H, m), 8.00 (H, t, = 8.4Hz), 8.19 (H, t, = 8.4Hz), 8.31 ( 3H, m), 8.61 (ÍH, d, = 6.3 Hz). e) 6- (6-Metupyridin-2-ü) metfloxi-3-f enfl-1, 2,4-triazolo f 3,4-aJphtalazana Sodium hydride (107 mg, from a 60% dispersion in oil) was added. to a solution of 2-hydroxymethyl-6-methypyridine (example 67 part b, 0.5 g), in anhydrous dimethylformamide (20 ml) under nitrogen and the reaction mixture was stirred at room temperature for 0.5 hour. To this mixture, 6-chloro-3-phene-1, 2,4-triazolo [3,4-a] phthalazine (example 67 part d, 330 mg) was added and the solution was heated to 80 ° C for 0, 25 hours After cooling, the solvent was removed under vacuum, and the residue was dissolved in dichloromethane (30 ml) and washed with water and brine. After drying (MgSO 4), the solution was filtered and evaporated by propordoning the desired product, which was recrystallized from a mixture of ethyl acetate and hexane to give the title compound (210 mg, mp 186-187 ° C). ? NMR (360 MHz, DMSO) d 2.52 (3H, s), 5.65 (2H, s), 7.25 (HH, d, = 7.7Hz), 7.49 (HH, d, J = 7.7 Hz), 7.58 (3H, m), 7.76 (H, t, J = 7.7 Hz), 7.94 (H, t, J = 7.6 Hz), 8.08 (H, t, J = 7.7 Hz), 8.30 (3H, m), 8.58 (H, d, J = 7.6 Hz); MS (ES +) m / e 368 [MH] +. Analysis calculated C, 71.32; H, 4.44; N, 18.53. C22H17N5O. H20 requires C, 71.22; H, 4.73; N, 18.88%.

EXAMPLE 70 6- (l-Methyl-l? R-l, 2,4-triazol-3-ylmethoxy) -3,7-diphenyl-l, 2,4-triazolof4,3-blpiridazipa This compound was prepared with a yield of 82% using a similar procedure to that described in Example 2, Step d, but using (l-metñ-1 ^ -1,2,4-triazol-3-y) methanol (prepared as described in Example 65) in place of 2-pyridinecarbinol. In this case, the reaction mixture was partitioned between water and ethyl acetate, adding saturated aqueous NaCl to aid in the separation of the layers. The aqueous layer was then extracted with ethyl acetate, and the combined organic extracts were dried (Na? SOt) and evaporated under vacuum. The residue was purified by flash chromatography (silica gel, 2% MeOH / CH2Cl2) and recrystallized from EtOAc-CH2Cl2. Data for the title compound: p.f. 229-233 ° C; ? NMR (360 MHz, CDCls) d 3.92 (3H, s), 5.61 (2H, s), 7.45-7.59 (6H, m), 7.68 (2H, dd, J = 7 , 9, J '= 1.6 Hz), 8.03 (HH, s), 8.05 (HH, s), 8.55 (2H, m); MS (ES +) m / e 384 [MHJ-. Analisys calculated C, 66.05; H, 4.34; N, 25.68. C 21 H 17 N 7 O requires C, 65.79; H, 4.47; N, 25.57%.

EXAMPLE 71 e-^ - Methyl ^ f -l ^^ - triazol-S-ilmetoxD-S -diphenyl-l ^^ -triazolo ^ -bl iridazine This compound was prepared in a yield of 40% using a similar procedure to that described in Example 2, Step d, but using (2-methy-2f '-l, 2,4-triazole-3-yl). ) methanol (prepared as described in example 66) in place of 2-pyriducarbinol. Data for the title compound: p.f. 198-202 ° C; ? NMR (360 MHz, CDOb) d 3.74 (3H, s), 5.67 (2H, s), 7.47-7.61 (8H,), 7.90 (H, s), 8.08 (ÍH, s), 8.42 (2H, m); MS (ES +) m / e 384 [MH] +. Analysis calculated C, 63.70; H, 4.45; N, 24.59. C21H17N7O. 0.7H2O requires C, 63.69; H, 4.68; N, 24.75%.

EXAMPLE 72 3,7-Difepil-6- (2J-r-l, 2,4-triazol-3-ylmethoxy) -l, 2,4-triazoIor 4,3-blpiridazine a) [2- (2 - (? rimetflsflanü) ethoxyetfl) -2ff-l, 2,4-triazol-3-fl-methanol l- (2- (thymimethyl) ethoxyethane) -li7-1, 2,4-triazole was dissolved (6.57 g) (prepared as described in Fugina et al, Heterocycles, 1992, 303-314) in THF (110 ml) and cooled to -70 ° C, after which, it was added, dropwise for 15 minutes maintaining the temperature at -70 ° C butu-Htl (23.12 ml of a 1.6 M solution in hexane). After one hour, DMF (2.4 ml, 1 eq mol) was added and the reaction mixture was allowed to warm to 0 ° C for 30 minutes. Saturated ammonium chloride solution (300 ml) was added and the mixture was extracted with ethyl acetate (2 x 300 ml). The organic layer was dried (Na? SOt), filtered and concentrated in vacuo to give a brown oil (6.5 g). This oil was dissolved in methanol (120 ml) and sodium borohydride (1.08 ml, 1 eq mol) was added in portions over 20 minutes. After one hour, the solvent was removed in vacuo and the residue was partitioned between water (50 ml) and dichloromethane (2 x 100 ml). The combined organic layers were washed with brine (1 x 30 ml), and dried (N 2-3? 4), filtered and concentrated in vacuo, yielding a clear oil which was subjected to chromatography on silica gel. 0-4% in dichloromethane, providing the desired compound (5 g) as a clear oil. ? NMR (250 MHz, CDCl 3) d 0.00 (9H, s), 0.93 (2H, t, J = 8.2 Hz), 3.63 (2H, t, J = 8.2 Hz), 4 , 87 (2H, s), 4.11 (HH, broad s), 5.28 (2H, s), 7.85 (HH, s). b) 3,7-Difenñ-6- [2- (2- (trimetüsña? ul) ethoxymeth) -2g-l, 2,4-triazol-3-ymetoxyJ-l, 2,4-triazolof4,3-bjpiridazine This compound was prepared using the procedures described in example 2 a), b), c) and d), using the product of example 72 a) in place of 2-pyriducarbinol. ? NMR (250 MHz, CDCb) d 0.00 (9H, s), 0.83 (2H, t, J = 8.2 Hz), 3.55 (2H, t, J = 8.2 Hz), 5 , 46 (2H, s), .78 (2H, s), 7.55-7.68 (8H, m), 8.00 (HH, s), 8.15 (HH, s), 8.45 (2H, d, J = 7.8 Hz). c) 3,7-Difenu-6- (2 g -l, 2,4-triazol-3-ylmethoxy) -l, 2,4-triazolo [4,3-b-pyridazine The product of example 72 was suspended, Step b) (0.68 g) in ethanol (10 ml) with 2N hydrochloric acid (21 ml) and heated at 65 ° C for 5.5 h. A saturated sodium carbonate solution was added dropwise until a solid precipitated and this was collected by filtration and washed several times with water in a funnel. The solid was recrystallized from methanol, allowing the desired product (0.245 g, m.p. = 248 ° C). ? NMR (360 MHz, d6-DMSO) d 5.61 (2H, s), 7.48-7.63 (6H, m), 7.44-7.77 (2H, m), 8.40 (4H , m), 14.13 (H, broad s); MS (ES +) m / e 370 [MH] +. Analysis calculated C, 65.02; H, 4.04; N, 26.35. C20H15N7O requires C, 65.03; H, 4.09; N, 26.54%.

EXAMPLE 73 6- 2-Methyl-2g-tetrazol-5-ylmethoxy) -3,7-diphenyl-l, 2,4-triazolo [4,3-bl-pyridazine a) 3,7-Difenu-l, 2,4-triazolo [4,3-b]? iridazin-6-one 4M NaOH (4.17 ml, 16.7 mmol) was added to a solution of doro-3,7-diphenol, 2,4-triazolo [4,3-b] pyridazine (from Example 2, Step c) (1.02 g, 3.34 mmol) in 1,4-dioxane (60 ml) and water (12 ml) and the solution was heated to reflux for 7.5 h with magnetic stirring. The mixture was then concentrated in vacuo and the aqueous residue was partitioned between water (200 ml) and diethyl ether (100 ml). The aqueous layer was acidified with 5 M HCl, until the pH was about 3. The resulting precipitated solid was collected by filtration, washed with water and then hexane and dried at 60 ° C under vacuum, yielding 0.8885 g ( 92%) of the title compound as a white solid. ? NMR (360 MHz, -DMSO) d 7.47-7.63 (6H, m), 7.71 (2H, dd, J = 8.0, J = 1.8 Hz), 8.31 (1H) , s), 8.46 (2H, m), 12.80 (1H, broad s); MS (ES +) m / e 289 [MH] +. b) 6 ^ (2-Metu-2 / f-tetiazol-5-fl methoxy) -3,7-diene: er? fl-l, 2,4-triazolo [4,3-b-pyridazine Sodium hydride (dispersion at 60% in oil, 31.2 mg, 0.780 mmol) to the product of Example 73, Step a) (0.15 g, 0.52 mmol) in anhydrous DMF (5 mL) and the mixture was stirred under nitrogen at room temperature for 45 min and then at 80 ° C for another 20 min. After letting cool, a solution of 5-chloromethane-2-methy-2i / -tetrazole (Moderhack, D., Chem. Ber., 1975, 108, 887-896) (0.103 g, 0.780 mmol) in anhydrous DMF (4 ml) was added. ) and the mixture was stirred at room temperature under nitrogen for 1-5 h and then at 80 ° C for 17 h. The mixture was then partitioned between water (30 ml) and ethyl acetate (40 ml). The aqueous layer was extracted again with ethyl acetate (9 x 40 ml) and the combined organic extracts were dried (MgSO 4) and evaporated under vacuum. The residue was recrystallized from EtOAc-CH2Cl2-MeOH by propyleneizing 0.1002 g (50%) of the title compound as a white solid:? .f. 228-233 ° C; ? NMR (360 MHz, COCk) d 4.36 (3H, s), 5.79 (2H, s), 7.47-7.60 (8H, m), 8.07 (1H, s), 8, 48 (2H, m); MS (ES +) m / e 385 [MH] +. Calculated Analysis C, 62.01; H, 4.13; N, 28.92. C20Hi6N8O. 0.17H2O requires C, 62.00; H, 4.25; N, 28.92%.

EXAMPLE 74 3,7-Diphenyl-6- (2-propii-2ff-1, 2,4-triazol-3-ylmethoxy) -l, 2,4-triazolo [4,3-blpyridaziPa a) 3- and 5- (Grc-Butyldimethylsiloxyetfl) -l-pro? 1-2-yl, 2,4-triazole A solution of 3- (tert-butyldimethyuanuximet) -l was added dropwise over 10 minutes. / -l, 2,4-triazole (prepared as described in EP-A-421210) (8.0 g, 37.5 mmol) in anhydrous DMF (25 ml) was added to a stirred mixture of sodium hydride (dispersion 60% in oil, 1.5 g, 37.5 mmol) and 1-iodopropane (4.4 mL, 45 mmol) in anhydrous DMF (100 mL), cooled under nitrogen to 0 ° C. The mixture was stirred under nitrogen at 0 ° C for 25 minutes, more sodium hydride (60% dispersion in oil, 0.45 g, 11.3 mmol) was added, and the mixture was stirred for another 30 minutes. Water (300 ml) was then added and the The mixture was extracted with ethyl acetate (3 x 100 ml). The combined organic extracts were washed with brine (100 ml), dried (a2S) and evaporated in vacuo. The residue was purified by flash chromatography (silica gel, 40-50% EtOAc / hexane, and alumina, 15% EtOAc / hexane) to give 4.10 g (43%) of 5- (tert-butyldimethylunsuccinate) -l- propyl-1Y-1,2,4-triazole and 2.97 g (31%) of 3 - (/ erc-butyldimethylsiloxane) -l-propylene-l, 2,4-triazole as colorless oils. 3- (fe / -c-Butfldimetüsñanüoximetfl) -l-pro? Fl-l / y-l, 2,4-triazole:? NMR (250 MHz, CDCl 3) d 0.12 (6H, s), 0.92 (9H, s), 0.93 (3H, t, J = 7.3 Hz), 1.91 (2H, sextuplete, J = 7.3 Hz), 4.09 (2H, t, J = 7.1 Hz), 4.77 (2H, s), 8.03 (ÍH, s). - (fó c-Butfldimetüsflanüoximetfl) -l-propfl-l / fl, 2,4-triazole: tH NMR (250 MHz, CDCl 3) d 0.10 (6H, s), 0.90 (9H, s), 0.95 (3H, t, J = 7.4 Hz), 1.92 (2H, sextuplet, J = 7.4 Hz), 4.19 (2H, m), 4.84 (2H, s), 7.81 (ÍH, s). bU2-Propfl-2H-l, 2,4-triazole-3-fl) methanol Aqueous NaOH (6 mL, 24 mmol) was added to a solution of 5- (tert-butyldimethylsuxynoxyet) -l-? rop-l-1 , 2,4-triazole (from Step a) (4.10 g, 16.1 mmol) in ethanol (18 ml) and methanol (36 ml) and the mixture was stirred at room temperature for 19 h and then at 45 ° C. C for another 5 h. The solvents were removed in vacuo and the residue was purified by flash chromatography (silica gel, EtOAc, then 10% MeOH / CH2C12) leaving 1.976 g (87%) of the title compound as a yellow oil: H NMR (250 MHz, CDCl 3) d 0.95 (3H, t, J = 7.4 Hz), 1.91 (2H, sextuplet, J = 7.4 Hz), 4.16 (2H, t, J = 7.3) Hz), 4.76 (2H, s), 7.81 (HH, s). c) 3,7-Difenu-6- (2-pro? fl-2g-l, 2,4-triazol-3-ylmethoxy) -l, 2,4-triazolo [4,3-b-pyridazine This compound was prepared with a yield of 4% using a procedure similar to that described in Example 2, Step d, but using (2-propyl-2-l, 2,4-triazol-3-yl) methanol (from Step b) in 2-pyriducarbinol. Data for the title compound: p.f. 211-213 ° C; ? NMR (250 MHz, CDCU) d 0.68 (3H, t, J = 7.4 Hz), 1.65 (2H, sextuplete, J = 7.4 Hz), 3.96 (2H, t, J = 7.4 Hz), 5.66 (2H, s), 7.45-7.63 (8H, m), 7.93 (HH, s), 8.09 (HH, s), 8.46 ( 2H, m); MS (ES +) m / e 412 [MH] +. Analisys calculated C, 66.75; H, 4.82; N, 23.60. C23H21N7O requires C, 67.14; H, 5.14; N, 23.83%.

EXAMPLE 75 3,7-Diphenyl-6- (l-propyl-l-l, 2,4-triazoI-3-ylmethoxy) -l, 2,4-triazolof 4,3-blpiridazine a) .l-Propfl-177-1, 2,4-triazole-3-y) methanol Aqueous 4M NaOH (4.3 mL, 17.4 mmol) was added to a solution of 2 > - (tert-butüdimetüsüanüoximetü) -l-propü-l / fl, 2,4-triazole (from example 74, Step a) (2.97 g, 11.6 mmol) in ethanol (13 ml) and methanol (26 ml) ) and the mixture was stirred at 45 ° C for 2 days. The solvents were removed in vacuo and the residue was purified by flash chromatography (silica gel, EtOAc, then 10% MeOH / CH2C12) to give 1.509 g (92%) of the title compound as a white solid:? NMR (250 MHz, CDCl 3) d 0.94 (3H, t, J = 7.4 Hz), 1.92 (2H, sextuple-te, J = 7.4 Hz), 4.10 (2H, t, J = 7.1 Hz), 4.76 (2H, s), 8.01 (ÍH, s). b) 3,7-Difenfl-6- (1-propylene-l, 2,4-triazol-3-ylmethoxy) -l, 2,4-triazolo [4,3-b]? iridazine This compound was prepared with a yield of 70% using a simulate procedure described in example 2, Step d, but using (l-propyl-l, 2,4-triazol-3-y) methanol (from Step a) instead of -? iridücarbinol. Data for the title compound: p.f. 212-214 ° C; ? NMR (360 MHz, CDCl 3) d 0.90 (3H, t, J = 7.4 Hz), 1.90 (2H, sextuplet, J = 7.3) Hz), 4.10 (2H, t, J = 7.0 Hz), 5.62 (2H, s), 7.45-7.58 (6H, m), 7.68 (2H, m), 8.03 (HH, s), 8.06 (HH, s), 8.56 (2H, m); MS (ES +) m / e 412 [MHJ +. Analisys calculated C, 67.51; H, 5.01; N, 23.86.

C23H21N7O requires C, 67.14; H, 5.14; N, 23.83%.

EXAMPLE 76 6- (l-Met-1-ft-midazole-4-Umethoxy) -3,7-diphenyl-l, 2,4-triazolof4,3-blpiridazine a) 4- and 5- (ferc-Butfldirnetñsñanñoximetñ) -l-metü-l í-imidazol A 1.6 M solution of butyl-thio in hexanes (10.2 ml, 16.4 mmol) was added to a solution of 5- (i.e. rc-butyldimethylsynoxymethyl) -l / '-imidazole (Amino, Y, Eto, H .; Eguchi, C, Chem. Pharm. Bull., 1989, 37, 1481-1487) (3.158 g, 14 , 9 mmol) in anhydrous THF (25 ml), cooled to -78 ° C under nitrogen. The mixture was stirred under nitrogen at -78 ° C for 30 min and then iodomethane (0.97 mL, 15.6 mmol) was added. The mixture was allowed to warm to room temperature and stirred for 5 hours. Water (150 ml) was then added and the mixture was extracted with diethyl ether (150 ml). The organic extract was washed with brine, dried (MgSO 4) and evaporated in vacuo. The residue was purified by flash chromatography (alumina, 40% EtOAc / hexane) to give 0.4732 g (14%) of 4- (ré? "C-butüdimetüsüanüoximetü) -l-metñ-l f-imidazole and 1,463 g ( 43%) of 5 - (/ e / -c-butüdimethylsuanumoxyetu) -l-metul-17-r-imidazole. 4- (ferc-Butfldimetüsüanñoximetü) -l-metñ-1 J, -imidazole:? NMR (250 MHz, CDCl 3) d 0,11 (6H, s), 0,93 (9H, s), 3,65 (3H, s), 4,68 (2H, s), 6,80 (ÍH, s), 7, 35 (ÍH, s). - (ferc-Butfldimetflsflanfloximetfl) -l-metfl-li7-imidazole:? NMR (250 MHz, CDCl 3) d 0.05 (6H, s), 0.88 (9H, s), 3.67 (3H, m), 4.65 (2H, s), 6.90 (OH, s), 7.41 (ÍH, s). b) (l-Methyl-lg-imidazole-4-fl) methanol 4 M aqueous NaOH (0.788 ml, 3.14 mmol) was added to a solution of 4- (tert-butyldimethynyl-oxymethyl) -l-methylene. imidazole (from Step a) (0.4732 g, 2.09 mmol) in ethanol (2.4 ml) and methanol (4.7 ml) and the mixture was stirred at 45 ° C for 2 days. The mixture was then evaporated in vacuo and the residue was purified by flash chromatography (silica gel, CH2Cl2-MeOH-NHS (aqueous): 80: 20: 2) giving 0.224 g (96%) of the title compound:? NMR (250 MHz, CDCl 3) d 3.66 (3H, s), 4.58 (2H, s), 6.84 (OH, s), 7.39 (OH, s). c) 6- (l-Metfl-lg-imidazol-4-flmetoxy) -3,7-dü: erul-l, 2,4-triazolo [4,3-b]? iridazine This compound was prepared with a yield of 44% using a simulate procedure described in Example 2, Step d, but using (l-methyl-L-imidazol-4-yl) methanol (from Step b) in place of 2-pyriducarbinol. Data for the title compound: p.f. 199-202 ° C; ? NMR (360 MHz, CDCl 3) d 3.63 (3H, s), 5.50 (2H, s), 6.88 (OH, s), 7.41-7.64 (9H, m), 8, 02 (ÍH, s), 8.56 (2H, m); MS (ES +) m / e 383 [MH] +. Calculated Analysis C, 69.02; H, 4.42; N, 21.55. C22H18N6O. 0.025H2O requires C, 69.01; H, 4.75; N, 21.95%.

EXAMPLE 77 6- (3-Methyl-3-fluoro-imidazol-4-ylmethoxy) -3,7-diphenyl-l, 2,4-triazole-4,3-blpiridazine a) (3-Methan-3ff-imidazole-4-ü) methanol 4 M aqueous NaOH (0.165 mL, 0.66 mmol) was added to a solution of 5- (tert-butyldimethyl) -l-met-1 / - imidazole (from Example 76, Step a) (0.100 g, 0.442 mmol) in ethanol (0.5 ml) and methanol (1 ml) and the mixture was stirred at room temperature duf before 2 hours and then at 50 ° C for 16 hours. hours. The mixture was then evaporated in vacuo and the residue was purified by flash chromatography (silica gel, CH? Ck-MeOH-NHs (aqueous); 80: 20: 2) to give 31.3 mg (63%) of the compound of the title:? NMR (250 MHz, CDCl 3) d 3.71 (3H, s), 4.62 (2H, s), 6.87 (H, s), 7.38 (H, s). b) 6- (3-Metu-3-imidazol-4-ylmethoxy) -3,7-diphen-l, 2,4-triazolo f4,3-bjpiridazine This compound was prepared in a yield of 30% using a siminate procedure to that described in Example 2, Step d, but using (3-metii-3 / -imidazole-4-y) methanol (from Step a) in place of 2-pyridi-carbinol. Data for the title compound: p.f. 195-196 ° C; ? NMR (250 MHz, CDCl 3) d 3.53 (3H, s), 5.52 (2H, s), 7.20 (1H, s), 7.44-7.65 (9H, m), 8, 04 (ÍH, s), 8.49 (2H, m); MS (ES +) m / e 383 [MH] +. Analysis calculated C, 68.31; H, 4.38; N, 21.55. C22Hi8N6O, 0.12H2O requires C, 68.70; H, 4.78; N, 21.85%.

EXAMPLE 78 6- (4-Metit-4g-l, 2,4-triazoI-3-ylmethoxy) -3,7-difatyl-l, 2,4-triazolo [4,3-blpiridazine This compound was prepared with a yield of 46% using a similar procedure to that descd in Example 2, Step d, but using (4-methyl-4H'-l, 2,4- ^ riazole-S-γ-methanol ( WO 95/34542) in place of 2- [alpha] -hydridcarbinol Data for the title compound: mp 230-235 [deg.] C; NMR (360 MHz, CDCl 3) d 3.50 (3H, s), 5.74 ( 2H, s), 7.45-7.62 (8H, m), 8.07 (HH, s), 8.12 (HH, s), 8.49 (2H, m); MS (ES +) m / e 384 [MHJ + .Analysis calculated C, 65.48, H, 4.34, N, 25.31, C21H17N7O requires C, 65.79, H, 4.47, N, 25.57%.

EXAMPLE 79 6- (5-Methyl-2 ---- r-l, 2,4-triazol-3-ylmethoxy) -3,7-diphenyl-l, 2,4-triazolof4,3-b1-pyridazipa a) (3,7-Diphenfl-l, 2,4-triazolo [4,3-b1-pyridazin-6-phloxy) acetonitrile Sodium hydride (60% dispersion in oil, 84.0 mg, 2.10 mmol) was added. to a stirred solution of 3,7-diphenol, 2,4-triazolo [4,3-b]? iridazin-6-one (from Example 73, Step a) (0.4021 g, 1.39 mmol) in anhydrous DMF (20 ml) under nitrogen and the reaction mixture was stirred at room temperature for 30 minutes and then at 80 ° C for 20 minutes. After allowing to cool, bromoacetonitrile (0.146 ml, 2.10 mmol) was added dropwise and the mixture was stirred at room temperature for 14 hours. The mixture was partitioned between ethyl acetate (100 ml) and water (100 ml), adding saturated aqueous NaCl to help separate the layers. The aqueous layer was extracted again with ethyl acetate (2 x 100 ml) and the combined organic extracts were dried (Na 2 SO 3) and evaporated under vacuum. The residue was purified by flash chromatography (silica gel, 2% MeOH / CH2Cl2) by binding 0.4566 g (100%) of the title compound as a color solid:? NMR (360 MHz, CDCl 3) d 5.11 (2H, s), 7.52-7.63 (8H, m), 8.12 (OH, s), 8.45 (2H, m); MS (ES +) m / e 328 [MH] +. b) 6- (5-Metü-2g-l, 2,4-triazol-3-ylmethoxy) -3,7-diphenol, 2,4-triazolo [4,3-bl? iridazine Sodium methoxide was added ( 2.6 mg, 0.048 mmol) was added to an ice-cooled solution of the product of Step a (0.280 g, 0.855 mmol) in anhydrous methanol (35 ml) under nitrogen and the mixture was stirred at room temperature under nitrogen for 20 minutes. and then at 50 ° C for 3 days, adding anhydrous dichloromethane (3 ml) to dissolve the solids. After allowing to cool, the mixture was neutralized by adding acetic acid (2.5 ml, 0.044 mmol). Acetic hydrazide (63 mg, 0.850 mmol) was then added and the mixture was stirred at room temperature for 20 hours and then at 50 ° C for 23 h. After allowing to cool, the brown solid was collected by filtration and washed with dichloromethane to give 230 mg of the intermediate acylimidrazone. This was heated at 145 ° C under high vap for 2 days and the residue was purified by preparative TLC (silica gel, 5% MeOH / CH 2 Cl 2) and recrystallized to give 61 mg (19%) of the title compound as a sóHdo white: pf 233-235 ° C; ? NMR (360 MHz, CDCl 3) d 2.50 (3H, s), 5.61 (2H, s), 7.41-7.52 (6H, m), 7.58-7.59 (2H, m) ), 7.96 (1H, s), 8.44 (2H, m); MS (ES +) m / e 384 [MH] +.

EXAMPLE 80 6- (3-Methyl-3iy-l, 2,3-triazol-4-ylmethoxy) -3,7-diphenyl-l, 2,4-triazolof4,3-blpiridazine a) 3-Metfl-3 fl, 2,3-triazole-4-carboxaldehyde A solution of 1.6 M butyl-thio hexanes (4.23 ml, 6.77 mmol) was added dropwise to a stirring solution of l-metü-l / fl, 2,3-triazole (0.500 g, 6.02 mmol) in anhydrous THF (20 ml), cooled to -70 ° C under nitrogen. The mixture was stirred at room temperature for 1 hour and then anhydrous DMF (0.465 ml, 6.02 mmol) was added and the mixture was allowed to warm to 0 ° C for 30 minutes. NH 4 Cl (25 ml) was then added and the mixture was extracted with ethyl acetate. The organic layer was dried (Na 2 SO 4) and evaporated in vacuo. The residue was purified by flash chromatography (silica gel, 40% EtOAc / hexane) to afford 0.128 g (19%) of the title compound as a yellow oil: * H NMR (360 MHz, dβ-DMSO) d 4.27 (3H, s), 8.45 (HH, s), 10. 01 (HH, s); MS (ES +) m / e 144 [M + MeOH + H] +, 111 [M] +. b) (3-Metü-3i7-l, 2,3-triazole-4-ü) -methanol Sodium borohydride (14.8 mg, 0.390 mmol) was added to a stirred solution of the product of Step a (0.128 g, 1.15 mmol) in anhydrous methanol ( , 1 mL), cooled to 0 ° C under nitrogen and the mixture was stirred at this temperature for 1 hour. Saturated aqueous NaCl (5 ml) was then added and the mixture was stirred for 10 minutes. The aqueous layer was extracted with ethyl acetate and the combined organic extracts were dried (Na 2 SO 4) and evaporated under vacuum. The residue was purified by flash chromatography (silica gel, 5% MeOH / CH2Cl) to give 86.3 mg (66%) of the title compound:? NMR (250 MHz, CDCl 3) d 4.10 (3H, s), 4.77 (2H, s), 7.53 (1H, s). c) 6- (3-Metü-3 í-l, 2,3-triazol-4-ibnetoxy) -3,7-diphenol, 2,4-triazolo [4,3-b] pyridazine This compound was prepared with a yield of 29% using a procedure simulate the one described in Example 2, Step d, but using (3-methy-3-γ-l, 2,3-triazole-4-Ü) methanol (from Step b) instead of 2- pyriducarbinol. Data for the title compound: p.f. 190-193 ° C; ? NMR (360 MHz, CDCls) d 3.94 (3H, s), 5.60 (2H, s), 7.49 (5H, s), 7.54-7.63 (3H, m), 7, 75 (HH, s), 8.08 (HH, s), 8.41 (2H, dd, J = 8.3, 1.6 Hz); MS (ES +) m / e 384 [MH] +.

Analysis calculated C, 62.88; H, 4.63; N, 24.10. C 21 H 17 N 7 O.H 2 O requires C, 62.83; H, 4.77; N, 24.42%.

EXAMPLE 81 3- (4-Methoxyphenyl) -6- (l-methyl-lH-l, 2,4-triazoI-3-ylmethoxy) -7-phenyl-l, 2,4-triazoiof4.3-b1-pyridazine This compound was prepared using the procedures described in example 2 a), b), c), d), using 4-methoxybenzyl hydrazide in place of benzoyl hydrazine in step c) and (l-met-l-1, 2) , 4-triazol-3-ü) methanol in place of 2-pyriducarbinol in step d). Data for the title compound: p.f. = 205-206 ° C. ? NMR (360 MHz, d6-DMSO) d 3.87 (6H, s), 5.54 (2H, s), 7.16-7.18 (2H, d, J = 7.2 Hz), 7, 49 (3H, m), 7.74 (2H, m), 8.36 (ÍH, s), 8.41-8.43 (2H, d, .7 = 7.2 Hz), 8.49 ( ÍH, s); MS (ES +) m / e 414 [MH + J.

EXAMPLE 82 6- (3-Methylpyridip-2-umethoxy) -3-phenyl-7- (piperidin-1-yl, 2,4-triazolof 4, 3-blpyridazine The compound was prepared using the procedures described in example 15, steps a), b), c), d) and e) using 3-methyl-2-pyridinemethanol in place of 2- ir ir id id id ir ir ir ir ir. Data for the title compound: p.f. = 160 ° C. ? NMR (250 MHz, CDCl 3) d 1.52-1.81 (6H, m), 2.45 (HH, s), 3.08-3.28 (4H,), 5.63 (HH, s) , 7.20-7.30 (HH, m), 7.38-7.52 (4H, m), 7.60 (HH, d, J = 7.6 Hz), 8.25-8.36 (2H, m); MS (ES +) m / e 401 [MH] +. Calculated Analysis C, 69.01; H, 6.00; N, 21.00. C23H2 N6O requires C, 68.98; H, 6.04; N, 20.99%.

EXAMPLE 83 7- (Morpholin-4-yl) -3-fePl-6- (pyridiP-2-ylmethoxy) -l, 2,4-triazoloH, 3-b] pyridazipa This compound was prepared using the procedures described in example 15 steps a), b), c), d) and e), using morpholine in place of piperidine in step c). Data for the title compound: p.f. = 214 ° C. ? NMR (360 MHz, CDCla) d 3.30-3.38 (4H, m), 3.88-3.94 (4H, m), 5.64 (2H, s), 7.30 (2H, t , J = 5.76 Hz), 7.45-7.58 (3H, m), 7.78 (ΔI, dt, J = 7.8, 1.7 Hz), 8.26-8.35 ( 2H, m), 8.67 (HH, d, J = 7.2 Hz); MS (ES +) m / e 389 [MH] +. Analysis calculated C, 64.37, H, 5.22; N, 21.62. C21H20N6O2. 0.15H2O requires C, 64.49; H, 5.22; N, 21.49%.

EXAMPLE 84 3-FePiI-7- (pyridip-3-yl) -6- (pyridyl-2-ylmethoxy) -l, 2,4-triazolof4,3-b] pyridazipa This compound was prepared using the procedures described in example 16, steps a), b) and c) using 3-pyridin boronic acid, in place of 4-ω-iridobuonic acid in step a). Data for the title compound: p.f. = 206 ° C. ? NMR (360 MHz, CDCl 3) d 5.66 (2H, s), 7.28 (ΔI, t, J = 6.5 Hz), 7.35 (ΔI, d, J = 7.8 Hz), 7 , 40-7.62 (4H, m), 7.72 (ΔH, td, 7.7, 1.7 Hz), 8.04 (ΔI, dt, J = 7.7, 1.7 Hz), 8,11 (ÍH, s), 8,43 (2H, dd, J = 9,6, 1,3 Hz), 8,64 (ÍH, d, J = 6,5 Hz), 8,74 (ÍH) , d, J = Hz), 8.95 (ÍH, s); MS (ES +) m / e 381 [MH] +. Calculated Analysis C, 69.33; H, 4.27; N, 21.57. CzaHißNßO. 0.15 (C2H5) 2 O requires C, 69.33; H, 4.51; N, 21.47%.

EXAMPLE 85 8-Methyl-6- (2-metit-2 - / - l, 2,4-triazoI-3-ylmethoxy) -3,7-diphenylamine, 2,4-triazolol-4,3-blirididazine This compound was prepared using the procedures described in the example 8 steps a), b), c) and d), using (2-methyl-2-Y-1, 2,4-triazole-3-yl) methanol (prepared using the condidones described in EP-A-421210) in place of 2-pyridine carbinol in step d). Data for the title compound: p.f. = 195 ° C. ? NMR (360 MHz, CDCl 3) d 2.57 (3H, s), 3.56 (3H, s), 5.57 (2H, s), 7.28 (2H, dd, J = 7.7, 2 , 2 Hz), 7.47-7.60 (6H, m), 7.84 (IH, s), 8.44 (2H, dd, J = 6.8, 2.0 Hz), 7.47 -7.60 (6H, m), 7.84 (OH, s), 8.44 (2H, dd, J = 6.8, 2.0 Hz); MS (ES +) m / e 398 [MH] +. Analisys calculated C, 66.52; H, 4.87; N, 23.74. C 22 H 19 N 7 O requires C, 66.49; H, 4.82; N, 24.67%.

EXAMPLE 86 6- (l-Methyl-lg-l, 2,4-triazoI-3-ylmethoxy) -7-fmorpholin-4-yl) -3-phenyl-l, 2,4-triazolo [4,3-blpiridazipa This compound was prepared using the procedures described in example 15, steps a), b), c), d) and e) using morpholine in place of piperidine in step c) and using (1-metü-li7-l, 2) , 4-triazol-3-ü) methanol (prepared using the conditions described in EP-A-421210) in place of 2-pyridine carbinol in step e). Data for the title compound: p.f. = 205-206 ° C. ? NMR (360 MHz, CDClg) S 3.28 (4H, t, J = 5.5 Hz), 3.88 (4H, t, J = 4.7 Hz), 3.94 (3H, s), 5 , 59 (2H, s), 7.21 (HH, s), 7.45-7.55 (3H, m), 8.05 (HH, s), 8.46 (2H, dd, J = 2 , 0., 6.9 Hz); MS (ES +) m / e 393 [MH] +. Calculated Analysis C, 58.55; H, 4.95; N, 28.42. C19H20N8O2 requires C, 58.15; H, 5.14; N, 28.55%.

EXAMPLE 87 6- (2-Methyl-2g-l, 2,4-triazoI-3-ylmethoxy) -7 - ('morpholin-4-yl) -3-phenyl-1, 2,4-triazol-4,3-blpyridazine This compound was prepared using the procedures described in Example 86, steps a), b), c), d) and e), using (2-metñ-2 / fl, 2,4-triazol-3-y) -methanol (prepared using the conditions described in EP-A-421210) in place of (l-metü-lff-l, 2,4-triazol-3-y) methanol in step e). Data for the title compound: p.f. = 210-211 ° C. ? NMR (360 MHz, CDCl 3) d 3.21 (4H, t, J = 4.7 Hz), 3.84 (4H, t, J = 4.7 Hz), 3.97 (3H, s), 5.63 ( 2H, s), 7.24 (HH, s), 7.47-7.56 (3H, m), 7.93 (HH, s), 8.27 (2H, dd, J = 1.7, 8.3 Hz); MS (ES +) m / e 393 [MH] +. Analysis calculated C, 58.34; H, 4.88; N, 28.33. C19H20 8O2 requires C, 58.15; H, 5.14; N, 28.55%.

EXAMPLE 88 7-Cyclohexyl-6- (2-methyl-2g-l, 2,4-triazoI-3-ylmethoxy) -3-phenyl-1, 2,4-triazolof4,3-blpiridazipa a) 6-Chloro-3-phene-l, 2,4-triazolof4,3-b] pyridazine 3,6-dichloropyridazine (20 g, 134 mmol) was suspended in xylene (200 ml) with benzoin-hydrazine (20, 1 g, 1.1 eq mol) and triethyl amine hydrochloride (20.3 g, 1.1 eq mol) and the reaction mixture was heated to reflux for 2 hours. The solvent was removed under high vacuum and the residue was purified by chromatography on silica gel using 1% methanol in dichloromethane as eluent to afford the desired product (17.1 g, m.p. = 199 ° C). ? NMR (250 MHz, CDCl 3) d 7.16 (ΔI, d, J = 9.7 Hz), 7.53-7.61 (3H, m), 8.16 (ΔI, d, J = 9.7 Hz), 8.44-8.50 (2H,); MS (ES +) m / e 231 [MH] +. b) 6- (2-Metu-2 / -l, 2,4-triazol-3-methoxy) -3-phene-1, 2,4-triazolo [4,3-b] pyridazine Sodium hydride (0.degree. , 32 g of a 60% dispersion in oil, 1.6 eq mol) to a solution of (2-metñ-2/7-l, 2,4-triazol-3-ü) methanol (0.9 g , 8.0 mmol) (prepared using the conditions described in EP-A-421210) in DMF (30 ml) and the reaction mixture was stirred at room temperature for 30 minutes. After this period, the product of example 88, Step a) (1.15 g, 5.0 mmol) was added as a solution in DMF (20 ml) and the reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with water (200 ml) and the aqueous was extracted with dichloromethane (4 x 150 ml). The combined extracts were dried (Na 2 SO 4), filtered and evaporated. The residue was purified by chromatography on silica gel using 4% MeOH in dichloromethane as eluent, yielding the desired product, (1.5 g, m.p. = 254 ° C). ? NMR (360 MHz, CDCl 3) d 3.98 (3 H, s), 5.61 (2 H, s), 6.90 (H, d, J = 9.8 Hz), 7.51-7.60 ( 3H, m), 7.94 (IH, s), 8.12 (H, d, J = 9.8 Hz), 8.39 (2H, dd, J = 9.6, 1.5 Hz); MS (ES +) m / e 308 [MHJ +. c) 7-Cyclohexfl-6- (2-methü-2 / Jl, 2,4-triazol-3-ümethoxy) -3-phene-l, 2,4-triazolo [4,3-b1? iridazine Water was added (12 ml) and sulfuric acid (0.24 ml, 1.5 eq mol, specific gravity = 1.84) to the product of example 88, Step c) (0.91 g, 3.0 mmol). The mixture was heated to 70 ° C and carboxylic acid cyidohexane (0.85 g, 2.3 eq mol) and silver nitrate (0.05 g, 0.1 eq mol) were added. The reaction mixture was degassed with nitrogen and an ammonium persulfate solution (1.0 g, 1.5 eq mol) in water (5 ml) was added via syringe for 5 minutes. After an additional hour of heating at 70 ° CThe reaction was poured onto ice, basified to pH 8-9 with aqueous ammonium hydroxide and extracted into dichloromethane (2 x 100 ml). The organic extracts were dried (Na? SQi), filtered and evaporated to give the desired product (0.21 g, m.p. = 192 ° C). ? NMR (250 MHz, CDCl 3) d 1.22-1.54 (6H, m), 1.72-2.04 (4H, m), 2.79 (1H, m), 3.98 (3H, s) ), 5.64 (2H, s), 7.48-7.60 (3H, m), 7.88 (IH, d, J = 0.9 Hz), 7.95 (IH, s), 8 , 34-8.38 (2H, m); MS (ES +) m / e 398 [MH] +. Analisys calculated C, 65.01; H, 5.82; N, 25.10%. C 21 H 23 N 7 O requires C, 64.78; H, 5.95; N, 25.18%.

EXAMPLE 89 7-Cyclohexyl-6-fl-methyl-lg-l, 2,4-triazol-3-ylmethoxy) -3-phenyl-l, 2,4-triazoIof4,3-b-pyridazipa This compound was prepared using the procedures described in example 88, steps a), b) and c), using (l-methyl-1-l, 2,4-triazol-3-y) methanol (prepared using the conditions described in EP-A-421210) in place of (2-metii-2 #-l, 2,4-triazol-3-y) methanol in step b). Data for the title compound:? NMR (360 MHz, CDCI3) d 1.20-1.52 (5H, m), 1.72-1.92 (3H, m), 1.20-2.03 (2H, m), 2.83-2.93 (1H, m) ), 3.94 (3H, s), 5.57 (2H, s), 7.48-7.56 (3H, m), 7.83 (HH, s), 8.06 (HH, s) , 8.48-8.54 (2H, m); MS (ES-) m / e 398 [MH] +. Analisys calculated C, 64.40; H, 5.95; N, 23.89%. C21H23N7O 0.15C6Hi4 0, lH2O requires C, 64.79; H, 6.33; N, 24.15%.

EXAMPLE 90 7-Cyclopentyl-6- (2-methyl-2iy-l, 2,4-triazol-3-ylmethoxy) -3-phenyl-l, 2,4-triazolof4,3-blpiridazipa This compound was prepared using the procedures described in example 88, steps a), b) and c), using cyclopentane carboxyHco acid in place of carboxylic acid cidohexane in step c). Data for the title compound:? NMR (360 MHz, CDCl 3) d 1.56-1.88 (6H, m), 2.04-2.16 (2H, m), 3.15-3.25 (HH, m), 3.97. (3H, s), 5.63 (2H, s), 7.51-7.57 (3H, m), 7.91 (HH, d, J = 0.8 Hz), 7.95 (HH, s), 8.37 (2H, dd, J = 6.6, 1.3 Hz); MS (ES +) m / e 376 [MHJ +. Calculated Analysis C, 63.65; H, 5.51; N, 25.26%. C20H21N7O. 0.2C2H6O requires C, 63.70; H, 5.82; N, 25.49%.

EXAMPLE 91 8-MetiI-6- (l-methyl-l-l, 2,4-triazol-3-imethoxy) -3,7-diphenyl-l, 2,4-triazoIof4,3-blpiridazine This compound was prepared using the procedures described in the example 8, steps a), b), c) and d), using (l-metü-l / -rl, 2,4-triazol-3-ü) methanol (prepared using the conditions described in EP-A-421210 ) in step d) in place of 2-pyriducarbinol. Data for the title compound:? NMR (360 MHz, CDCl 3) d 2.56 (3H, s), 3.87 (3H, s), 5.49 (2H, s), 7.36-7.57 (8H, m), 7, 97 (ÍH, s), 8.50-8.56 (2H, m); MS (ES +) m / e 398 [MH] +. Analysis calculated C, 66.45; H, 4.36; N, 23.95. C 22 H 19 N 7 O requires C, 66.49; H, 4.82; N, 24.67%.

EXAMPLE 92 7-Cyclobutyl-6- (l-methyI-lg-l, 2,4-triazol-3-ylmethoxy) -3-fepyl-l, 2,4-triazoyl-4,3-blpiridazine This compound was prepared using the procedures described in example 88, steps a), b) and c), using (l-metü-li / -l, 2,4-triazol-3-y) methanol (prepared using the described conditions in EP-A-421210) in place of (2-methy-2 /, l-l, 2,4-triazole-3-yl) methanol in step b) and using carboxyl carboxyl acid in place of ddohexane carboxy in stage c). Data for the title compound:? NMR (360 MHz, CDCl 3) d 1.88-2.05 (2H, m), 2.06-2.39 (2H, m), 2.40-2.50 (2H, m), 3.67. -3.71 (HH, m), 3.95 (3H, s), 5.53 (2H, s), 7.49-7.85 (3H, m), 8.06 (HH, s), 8.49 (HH, s), 8.51 (2H, d, J = 1.3 Hz); MS (ES +) m / e 362 [MH] +. Calculated Analysis C, 62.98; H, 5.07; N, 26.90. C19H19N7O requires C, 63.14; H, 5.30; N, 27.13%.

EXAMPLE 93 7-tert-Butyl-6- (2-methyl-2H-l, 2,4-triazoI-3-ylmethoxy) -3-fepyl-l, 2,4-triazolof4,3-blpiridazine This compound was prepared using the procedures described in example 88, steps a), b) and c) using trimeti-acetic acid instead of cyclohexane carboxy-acid in step c). Data for the title compound: * H NMR (360 MHz, CDCl 3) d 1.41 (9H, s), 3.97 (3H, s), 5.65 (2H, s), 7.50-7, 57 (3H, m), 7.96 (HH, s), 8.01 (HH, s), 8.36-8.38 (2H, m); MS (ES +) m / e 364 [MH] +. Calculated Analysis C, 62.38; H, 5.83; N, 26.45. C19H21N7O 0.15H2O requires C, 62.33; H, 5.86; N, 26.78%.

EXAMPLE 94 7-Cyclobutyl-6- (2-methyl-2-pyr-l, 2,4-triazol-3-ylmethoxy) -3-pheoyl-l, 2,4-triazolof4,3-b1-pyridazine This compound was prepared using the procedures described in example 88, steps a), b) and c) using carboxyco acid cidobutane in place of carboxyco acid cidohexane in step c). Data for the title compound: p.f. = 228 ° C. ? NMR (360 MHz, CDCls) d 1.86-1.98 (HH, m), 2.00-2.22 (3H, m), 2.26-2.45 (2H, m), 3.54 -3.68 (HH, m), 3.97 (3H, s), 5.59 (2H, s), 7.47-7.60 (3H, m), 7.86 (HH, d, J = 1.6 Hz), 7.94 (HH, s), 8.35-8.42 (2H, m); MS (ES +) m / e 397 [MH] +. Calculated Analysis C, 63.38; H, 5.22; N, 27.19. C19H19N7O requires C, 63.14; H, 5.30; N, 27.13%.

EXAMPLE 95 7-Ethyl-6- (2-methyl-2g-1, 2,4-triazol-3-ylmethoxy) -3-fepyl-1, 2,4-triazolof 4, 3-bipyridazipa This compound was prepared using the procedures described in the example 88, steps a), b) and c) using propionic acid in place of cyclohexane carboxyHco acid in step c). Data for the title compound:? NMR (360 MHz, CDCl 3) d 1.31 (3H, t, J = 7.4 Hz), 2.71 (2H, q, J = 7.4 Hz), 3.99 (3H, s), 5 , 63 (2H, s), 7.47-7.60 (3H, m), 7.87 (IH, s), 7.94 (IH, s), 8.34-8.42 (2H, m ); MS (ES +) m / e 336 [MH] +. Analysis calculated C, 60.85; H, 5.39; N, 28.22. C17H17N7O 0, lH2O requires C, 60.50; H, 4.98; N, 27.77%.

EXAMPLE 96 7-te, c-Butyl-6- (l-methyl-l-l, 2,4-triazol-3-ylmethoxy) -3-phenyl-l, 2,4-triazoior4,3-blpiridazipa This compound was prepared using the procedures described in the example 88, steps a), b) and c) using (l-metü-lí-l, 2,4-triazol-3-ü) methanol (prepared using the described in EP-A-421210) in place of (2-methy-2 / Jl, 2,4-triazol-3-y) methanol in step b) and using trimethaacetic acid instead of carboxy carboxylic acid in stage c). Data for the title compound:? NMR (360 MHz, CDCl 3) d 1.45 (9H, s), 3.95 (3H, s), 5.59 (2H, s), 7.43-7.60 (3H, m), 7, 95 (HH, s), 8.06 (HH, s), 8.49-8.55 (2H, m); MS (ES +) m / e 364 [MH] +. Analisys calculated C, 62.03; H, 5.58; N, 25.67. C19H21N7O 0.12C6Hi4 0.33H2O requires C, 62.36; H, 6.19; N, 25.84%.

EXAMPLE 97 7-Ethyl-6- (l-methyl-lJ-r-l, 2,4-triazoI-3-ylmethoxy) -3-phenyl-l, 2,4-triazolof4,3-blpiridazipa This compound was prepared using the procedures described in example 88, steps a), b) and c) using (l-metul-li-rl, 2,4-triazol-3-yl) methanol (prepared using the conditions described in EP-A-421210) in place of (2-methy-2-fl, 2,4-triazole-3-yl) methanol in step b) and using propionic acid in place of carboxyHoic acid in stage c) . Data for the title compound:? NMR (360 MHz, CDCl 3) d 1.31 (3H, t, J = 7.4 Hz), 2.68-2.84 (2H, q, J = 7.4 Hz), 3.94 (3H, s), 5.56 (2H, s), 7.43-7.64 (3H, m), 7.82 (HH, s), 8.06 (HH, s), 8.46-8.60 (2H, m); MS (ES +) m / e 336 [MH] +. Calculated Analysis C, 60.91; H, 4.73; N, 29.07. C17H17N7O requires C, 60.88; H, 5.11; N, 29.24%.

EXAMPLE 98 7-Methyl-6- (2-netyl-2-H-1, 2,4-tria-zol-3-ylmethoxy) -3-phenyl-1, 2,4-triazolo [4,3-blpiridaziPa This compound was prepared using the procedures described in Example 5, steps c) and d) using (2-methyl-2 / -l, 2,4-triazol-3-yl) methanol (prepared using the conditions described in EP -A-421210) instead of 2-? Iridü carbinol in step d). Data for the title compound:? NMR (360 MHz, CDCl 3) d 2.34 (3H, d, J = 1.2 Hz), 3.99 (3H, s), 5.62 (2H, s), 7.47-7.60 (3H, m), 7.85 (IH, d, J = 1.3 Hz), 7.94 (IH, s), 8.34-8.41 (2H, m); MS (ES +) m / e 322 [MH] +. Analisys calculated C, 60.26; H, 4.45; N, 30.18. ÓHISNTO 0.05 C6Hu requires C, 60.12; H, 4.86; N, 30.11%.

EXAMPLE 99 7-fl-Methylcyclobutyl) -6-f2-methyl-2-flu-1, 2,4-triazol-3-ylmethoxy) -3-fePl-1, 2,4-triazolof4,3-blpiridazine This compound was prepared using the procedures described in example 88, steps a), b) and c) using 1-methybutobutane carboxyHCO (Journal of Organometallic Chemistry, 1988, 352, 263-272) in place of carboxyHcdo ddohexane acid in the stage c) Data for the title compound:? NMR (360 MHz, CDCls) d 1.51 (3H, s), 1.80-1.92 (ÍH, m), 2.02-2.26 (3H, m), 2.34-2.45 (2H, m), 3.95 (3H, s), 5.60 (2H, s), 7.47-7.60 (3H, m), 7.47 (1H, s), 7.94 ( ÍH, s), 8.38 (2H, dd, J = 6.6, 1.7 Hz); MS (ES +) m / e 376 [MH] +. Analysis calculated C, 63.82; H, 5.53; N, 25.82. C20H21N7O requires C, 63.98; H, 5.64; N, 26.12%.

EXAMPLE 100 7-MetiI-6-ü-metü-lg-l, 2,4-triazot-3-ylmethoxy) -3-phenylim, 2,4-triazoIo [4,3-blpiridazÍPa This compound was prepared using the procedures described in Example 5, steps c) and d) using (l-methylll, 2,4-triazole-3-yl) methanol (prepared using the conditions described in EP-A- 421210) in place of hydroxymethyl pyridine in step d). Data for the title compound:? NMR (360 MHz, CDCl 3) d 2.37 (3H, s), 3.95 (3H, s), 5β5 (2H, s), 7.45-7.59 (3H, m), 7.83 ( HH, d, J = 1.2 Hz), 8.07 (HH, s), 8.43-8.54 (2H, m); MS (ES-) m / e 322 [MH] +. Analisys calculated C, 59.51; H, 4.45; N, 29.88. C 16 H 15 N 7 O requires C, 59.80; H, 4.71; N, 30.51%.

EXAMPLE 101 7-Cyclobutyl-3-phepyl-6- 2g-l, 2,4-triazoI-3-ylmethoxy) -l, 2,4-triazoIof4,3-blpiridazipa This compound was prepared in a manner analogous to that described in example 102, steps a), b) and c) by using carboxycarboxylic acid instead of carboxyco cidopentane acid in step a), using benzoic hydrazide instead of acid hydrazide 2-thiophene carboxyHco in step b) and using 3-hydroxyethane-2- [2- (ttimetüsflanü) ethoxyJmetü-2 / f-1,2,4-triazole (prepared in Example 72, Step a) instead of 2 -hydroxymethyridine in step c). This was done by following the procedure of Example 72, Step c) by propranning the title compound. Data for the title compound:? NMR (360 MHz, d6-DMSO) d 1.74-1.90 (1H, m), 1.90-2.29 (5H, m), 3.50-3.71 (1H, m), 5 , 54 (2H, s), 7.48-7.69 (3H, m), 8.14 (HH, d, J = 1.0 Hz), 8.30-8.49 (2H, m), 8.52 (ÍH, broad s); MS (ES +) m / e 348 [MH] +. Calculated AIXysis C, 61.93; H, 4.65; N, 27.58. C18H1 N O3 0.17H2O requires C, 61.69; H, 4.99; N, 27.98%.

EXAMPLE 102 7-Cyclopeptyl-6- (pyridin-2-ylmethoxy) -3-phthiophen-2-yl) -l, 2,4-triazolof4,3-blpiridazipa a) 3,6-Diclyl-4-cidopenthlpyridazine 3,6-Dichloro-iridazine (10 g) was suspended in water (200 ml), concentrated H2SO4 (19.7 g) and carboxy hydrocarboxylic acid (32.7 g) were added. ) and the reaction was degassed under N2 at 70 ° C. Silver nitrate (2.28 g) was added, followed by addition, dropwise of ammonium persulfate (45.9 g) in water (120 ml). After an hourly adidonal heating at 70 ° C, the reaction was poured onto ice, basified to pH 8-9 with aqueous ammonium hydroxide and extracted into ethyl acetate (3 x 500 ml), dried (MgSO 4). 4) and evaporated to dryness. It was purified with ethyl hexane-acetate mixtures to obtain the pure product (13.4 g). 1 H NMR (360MHz, CDCl 3) d 1.57 (2H, m), 1.82 (4H, m), 2.20 (HH, m), 3.30 (HH, m), 7.38 (HH, s); MS (ES-) m / e 217 [MH] -. b) 6-Chloro-7-ddo-en-3- (thiophen-2-y) -l, 2,4-triazolo [4,3-b] pyridazine. 3,6-Diene-4-dclo-en-tripyridazine was heated. (1.6 g) was added with 2-thiophene carboxy hydroxide (1.16 g) and triethylamine hydrochloride (1.16 g) in xylene (10 ml) at 140 ° C for 18 hours. The cooled reaction was partitioned between ethyl acetate and sodium carbonate solution, the organic phase was separated, dried (MgSO 4), evaporated to dryness and purified on silica gel eluting with mixtures of hexane-ethyl acetate, Propounding the 7- and 8-dclopentyl isomers. ? NMR (360 MHz, CDCfe) d 1.89 (6H, m), 2.30 (2H, m), 6.93 (HH, s), 7.23 (HH, dd, J = 5.2, 3 , 9 Hz), 7.54 (ΔI, dd, J = 4.9, 0.9 Hz), 8.25 (ΔI, dd, J = 3.8, 1.0 Hz); MS (ES-) m / e 305 [MHJ- (less polar isomer). ? NMR (360 MHz, CDCl 3) d 1.70 (6H, m), 2.23 (2H,), 3.36 (HH, m), 7.24 (HH, m), 7.55 (HH, dd , J = 7.0, 1.6 Hz), 7.99 (HH, s), 8.24 (HH, dd, = = 5.3, 1.6 Hz); MS (ES-) m / e 305 [MH] - (more polar isomer). c) 7-Cyclo? entfl-6 - (? iridin-2-flmetoxy) -3- (thiophen-2-y) -l, 2,4-triazolo [4,3-b]? iridazine 2-hydroxymethylpyridine was dissolved (56 mg) in dimethylformamide (2 ml) under N2 Sodium hydride (60% w / w in oil, 21 mg) was added, followed after 5-10 min by 6-chloro-7-cidopentyl-3- (thiophen-2-yl) -l, 2,4-triazolo [4,3-b] pyridazine (100 mg). The reaction was stirred at room temperature for 18 hours, partitioned between ethyl acetate and water, the organic phase was separated, dried (MgSO 4) and evaporated to dryness. Recrystallization from ethyl acetate, ether or methanol gave the pure product. aH NMR (250 MHz, CDCls) d 1.73 (6H, m), 2.16 (2H, m) 3.38 (1H, m), 5.68 (2H, s), 7.21 (1H, m), 7.28 (HH, m), 7.51 (2H, m), 7.77 (HH, m), 7.88 (HH, d, J = 1.1Hz), 8.15 (HH) , m), 8.65 (H, m); MS (ES-) m / e 377 [MH] -.

Lié EXAMPLE 103 7-Cyclopepti-3-2,4-difluoropheopyl) -6- (l-methyl-lg-l, 2,4-tria2!? I-3-ylmethoxy) -l, 2,4-triazoIof4,3 - blpiridazine It was prepared in a manner analogous to that described in example 102b using 2,4-difluorobenzoic acid hydrazide and example 102c using (l-methyl-l, -1, 2,4-triazol-3-y) methanol, providing the title compound. ? NMR (360 MHz, CDCl 3) d 1.75 (6H, m), 2.14 (2H, m) 3.24 (1H, m), 3.93 (3H, s), 5.42 (2H, s) ), 7.14 (2H, m), 7.86 (HH, s), 7.90 (HH, m), 8.04 (HH, s); MS (ES-) m / e 412 [MH] -.

EXAMPLE 104 7-Cyclopeptyl-6-fl-methyl-lg-l, 2,4-triazol-3-ylmethoxy) -3- (thiofep-2-H) -l, 2,4-tria2? Lof4,3-blpiridazine Prepared in a manner analogous to that described in Example 102b using 2-thiophene carboxyHcoic acid hydrazide and Example 102c using (l-methan-L, 2,4-triazole-3-yl) methanol, affording the compound of the title. ? NMR (250 MHz, CDCl 3) d 1.32 (6H, m), 2.14 (2H, m), 3.28 (1H, m), 3.95 (3H, s), 5.61 (2H, s), 7.24 (HH, m), 7.50 (HH, dd, J = 1.2, 5.1 Hz), 7.84 (HH, d, J = 1.1 Hz), 8, 07 (ÍH, s), 8.25 (ÍH, dd, J = 3.7, 1.1 Hz); MS (ES-) m / e 382 [MH] -.

EXAMPLE 105 7-CyclopeptiI-6-C2-methyI-2g-1, 2,4-triazol-3-ylmethoxy) -3- (thiophen-2-yl-1, 2,4-triazoloyl-4,3-blpiridazipa It was prepared with a procedure analogous to that described in Example 102b using 2-thiophene carboxyH-hydrazide hydrazide and Example 102c using (2-methyl-2-yl-l, 2,4-triazol-3-yl) methanol, providing the title compound. aH NMR (250 MHz, CDCla) d 1.73 (6H, m), 2.08 (2H, m), 3.18 (H, m), 4.03 (3H, s), 5.69 (2H, s), 7.24 (ÍH, m), 7.52 (HH, dd, J = 5.0, 1.2 Hz), 7.88 (HH, d, J = 1.1 Hz), 8.01 (HH, s), 8.18 (HH) , dd, J = 3.7, 1.1 Hz); MS (ES-) m / e 382 [MH] -.

EXAMPLE 106 7-Cyclopeptyl-6- (2-methyl-2g-l, 2,4-triazol-3-ylmethoxy) -3- (pyridin-4-yl) -l, 2,4-triazoIof4,3-blpiridazipa It was prepared with a procedure analogous to that described in the example 102b using isonicotinic hydrazide and example 102c using (2-methyl-2-yl-l, 2,4-triazol-3-yl) methanol, propounding the title compound. * H NMR (250 MHz, CDCl 3) d 1.75 (6H, m), 2.12 (2H, m), 3.22 (1H, m), 4.02 (3H, s), 5.68 ( 2H, s), 7.96 (HH, m), 8.43 (2H, d, J = 6.2Hz), 8.83 (2H, d, J = 6.0 Hz); MS (ES-) m / e 377 [MH] -.

EXAMPLE 107 7-Cyclopentyl-3- (2-fluorofepil) -6- (l-methyl-lg-l, 2,4-triazol-3-ylmethoxy) -l, 2,4-triazoIof4,3-bl pyridazine It was prepared with a procedure analogous to that described in the example 102b using hydrazide o-fluorobenzyl and Example 102c using (1-methyl-1-l, 2,4-thiazole-3-yl) methanol to provide the title compound. * H NMR (250MHz, CDCI3) d 1.69 (6H, m), 2.12 (2H, m), 3.23 (HH, m), 3.93 (3H, s), 5.41 (2H, s), 7.29 (2H, m), 7.51 (HH) , m), 7.85 (HH, d, J = 0.7 Hz), 7.97 (1H, m), 8.04 (1H, s); MS (ES-) m / e 394 [MH] -. 113 EXAMPLE 108 7-Cyclopeptyl-3- (2-fluorophenyl) -6- (2-methyI-2g-1, 2,4-triazoth-3-ylmethoxy) -l, 2,4-triazolor-4-blpyridazine It was prepared with a procedure analogous to that described in Example 102b using hydrazide o-fluorobendhca and Example 102c using (2-methan-2 7-l, 2,4-triazol-3-yl) methanol, propounding the Title. ? NMR (250 MHz, CDCl 3) d 1.72 (6H, m), 2.08 (2H, m), 3.19 (1H, m), 3.84 (3H, s), 5.49 (2H, s), 7.32 (2H, m), 7.58 (1H, m), 7.87 (2H, m), 7.90 (1H, m); MS (ES-) m / e 394 [MH] -.

EXAMPLE 109 7-Cyclopentin-3- (2-fluorofepiI) -6- (pyridip-2-ylmethoxy) -1.2,4-triazoIor4,3-blpiridazipa It was prepared with a procedure analogous to that described in example 102b using hydrazide o-fluorobendHca and example 102c using 2-hydroxymethyl pyridine, propordinating the title compound. ? NMR (250 MHz, CDCl 3) d 1.74 (6H, m), 2.16 (2H, m), 3.32 (1H, m), 5.48 (2H, s), 7.25 (3H, m), 7.42 (HH, m), 7.51 (HH, m), 7.51 (HH, m), 7.71 (HH, d, J = 1.1Hz), 7.88 (HH) , d, J = 0.7 Hz), 8.60 (1H, m); MS (ES +) m / e 390 [MH] -.

EXAMPLE 110 7-Cyclopentyl-3- 2,4-difluoropropyl) -6- (2-methyl-2g-l, 2,4-triazol-3-ylmethoxy) -l, 2,4-triazolor4,3-blpiridazine It was prepared with a procedure analogous to that described in example 102b using 2,4-difluorobenzoic acid hydrazide and example 102c using (2-methy-2Zf-1, 2,4-triazol-3-y) methanol, providing the title compound. ? NMR (250 MHz, CDCI3) d 1.73 (6H, m), 2.09 (2H, m), 3.18 (1H, m), 3.85 (3H, s), 5.49 (2H, s), 7.07 ( 2H, m), 7.90 (3H, m); MS (ES +) m / e 412 [MHJ-.

EXAMPLE 111 7-Cyclopeptyl-3-phenyl-6-pyridip-2-ylmethoxy) -l, 2,4-triazolof4 ^ -blpiridazipa It was prepared with a procedure analogous to that described in example 102b using benzoic hydrazide and example 102c using 2-hydroxymethyl pyridine to provide the title compound. ? NMR (250 MHz, CDCl 3) d 1.76 (6H, m), 2.18 (2H, m), 3.34 (1H, m), 5.62 (2H, s), 7.30 (1H, m), 7.50 (4H, m), 7.77 (IH, m), 7.88 (IH, d, J = 0.7Hz), 8.36 (2H, m), 8.65 (H , m); MS (ES +) m / e 372 [MH] -.

EXAMPLE 112 7-Cyclopentyl-8-methyl-6- (2-methyl-2 / -1,2,4-triazole-3-i-methoxy) -3-phenyl-1,2,4-triazoloyl-4,3-bipyridazide It was prepared with a procedure analogous to that described in example 102a using 3,6-dimer-4-methylazidazine, example 102b using benzoic hydrazide and example 102c using (2-methyl-2/7-l, 2 , 4-triazole-3-ü) methanol, propordinating the title compound. ? NMR (250 MHz, CDCk) d 1.63 (4H, m), 1.83 (4H, m), 2.74 (3H, s), 3.46 (1H, m), 3.94 (3H, s), 5.57 (2H, s), 7.51 (3H, m), 7.95 (1H, s), 8.36 (2H, m); MS (ES-) m / e 390 [MH] -.

EXAMPLE 113 7-Cyclopentyl-3-phenyl-6- (2-γ-l, 2,4-triazol-3-ylmethoxy) -l, 2,4-triazolof4,3-blpiridazipa This compound was prepared using the procedures described in the example 102, steps a), b) and c) using benzoic hydrazide instead of 2-thiophene acid hydrazide carboxyHC in step b) and using 3-ldroxy? net? -2- [2- (trimethyung) ethoxy] rr? ethyl-2yr-l, 2,4-triazole (prepared in Example 72, Step a) instead of 2-hydroxymethylpyridine in step c).

This was followed by the procedure described in Example 72, Step c), propordinating the title compound. Data for the title compound:? NMR (250 MHz, CDCI3) d 1.74 (6H, m), 2.11 (2H, m), 3.12 (IH, broad s), 3.22 (IH, m), 5.58 (2H, m), 7.50 (3H, m ), 7.85 (ΔI, d, J = 0.7 Hz), 8.27 (1H, m), 8.37 (2H, m); MS (ES-) m / e 362 [MHJ-.

EXAMPLE 114 3- (4-MetiIfeniI) -7-phenyl-6- (pyridin-2-ylmethoxy) -l, 2,4-triazolof4,3-blpiridazipa This compound was prepared using the procedures described in example 2, steps a), b), c) and d) except that in step c) hydrazide / J-toluica was used instead of benzoin hydrazide. Data for the title compound:? NMR (250 MHz, CDCl 3) d 2.45 (3H, s), 5.68 (2H, s), 7.29-7.39 (1H, m), 7.51-7.55 (3H, m) ), 7.66-7.77 (3H, m), 8.07 (HH, s), 8.18-8.31 (2H, m), 8.64 (HH, broad d, J = 5, 6 Hz). MS (ES-) m / e 394 [MH] -.

EXAMPLE 115 3- (4-Methylphenyl) -6- (3-methylpyridin-2-ylmethoxy) -7-phenyl-l, 2,4-triazoIof4,3-blpiridazipa This compound was prepared using the procedures described in the example 2, steps a), b), c) and d) except that in step c) hydrazide was used > -toluic instead of benzoyl hydrazide; and in step d) 3-methan-2-? iridinemethanol was used in place of 2-pyridflcarbinol. Data for the title compound: * H NMR (250 MHz, CDCl 3) d 2.31 (3H, s), 2.45 (3H, s), 5.68 (2H, s), 7.24 (1H, dd, J = 7.7, 4.9 Hz), 7.32-7.46 (5H, m), 7.54-7.64 (3H, m), 8.03 (1H, s), 8 , 30 (2H, d, J = 8.3 Hz), 8.46 (ÍH, broad d, J = 5.5 Hz). MS (ES-) m / e 408 [MH] -.

EXAMPLE 116 6- (1-Ethyl-1-r-imidazol-2-ylmethoxy) -3- 4-methylphenyl) -7-phenyl-1, 2,4-triazoior 4,3-blpiridazipa This compound was prepared using the procedures described in example 2, steps a), b), c) and d) except that in step c) hydrazide / β-toluic was used in place of benzoyl hydrazide; and in step d) l-etii-2- (hydroxymethyl) imidazole was used in place of 2-pyridinecarbinol. Data for the title compound:? NMR (250 MHz, CDCl 3) d 1.14 (3 H, t, J = 7.3 Hz), 2.46 (3 H, s), 3.88 (2 H, q, J = 7.3 Hz), 5 , 62 (2H, s), 6.98 (ÍH, d, J = 1.3 Hz), 7.10 (1H, d, J = 1.2 Hz), 7.34-7.54 (7H, m), 8.02 (ÍH, s), 8.40 (2H, d, J = 8.3 Hz). MS (ES-) m / e 411 [MHJ-.

EXAMPLE 117 3-FePlI-6- (pyridiP-2-ylmethoxy) -7- (thiomorpholin-4-yl) -l, 2,4-triazolo [4,3-b-pyridazide This compound was prepared using the procedures described in example 15, steps a), b), c), d) and e) except that thiomorpholine was used in place of piperidine in step c). Data for the title compound:? NMR (360 MHz, CDCl 3) d 2.81-2.84 (4H, m), 3.56-3.58 (4H, m), 5.62 (2H, s), 7.29-7.32. (2H, m), 7.49-7.53 (4H, m), 7.79 (ΔH, td, J = 7.7, 1.7 Hz), 8.31 (2H, dd, J = 8 , 3, 2.4 Hz), 8.64-8.66 (2H, m). MS (ES-) m / e 405 [MH] -. Calculated Analysis C, 62.30; H, 4.90; N, 20.60. C21H20N6OS requires C, 62.36; H, 4.98; N, 20.78%.

EXAMPLE 118 6-r2- (4-Methylthiazol-5-yl) ethoxy-3,7-diphenyl-l, 2,4-triazolof4,3-b1-pyridazine This compound was prepared using the procedure described in Example 61 except that 5- (2-hydroxyethyl) -4-methylthiazole was used in place of 4-hydroxymethyl alcohol.

Data for the title compound: MS (ES-) m / e 414 [MH] -. HPLC 90% (desdende en un HP1090 using a Hichrom S50DS2 column, 23 cm, flow rate of 1 ml / min and acetonitrile at 70% / phosphate buffer pH 3.5 as mobile phase).

EXAMPLE 119 ^ ±) -7- 2-Methylpyrrolidin-l-ip-3-phenyl-6-pyridyl-2-ylmethoxy) -l, 2,4-triazoIo [4,3-blpiridazipa This compound was prepared using the procedures described in example 15, steps a), b), c), d) and e) except that 2-methy? IrroHdine (racemic) was used in place of piperidine in step c). Data for the title compound: * H NMR (360 MHz, CDCb) d 1.17 (3 H, d, J = 6.1 Hz), 1.64-1.69 (H, m), 1.87- 2.24 (3H, m), 3.42-3.48 (HH, m), 3.67-3.74 (HH, m), 4.23-4.28 (HH, m), 5, 60 (2H, s), 6.81 (HH, s), 7.29 (HH, dd, J = 7.5, 4.8 Hz), 7.42-7.49 (4H, m), 7 , 74 (ΔI, td, J = 7.7, 1.8 Hz), 8.27-8.30 (2H, m), 8.66 (ΔI, broad d, J = 5.5 Hz). MS (ES-) m / e 387 [MH] +. Analysis calculated C, 68.24; H, 5.76; N, 21.67. C 22 H 22 N 6 O requires C, 68.38; H, 5.74; N, 21.74%.

EXAMPLE 120 6-fl-Methyl-lg-l, 2,4-triazol-3-ylmethoxy) -3-phenyl-7- (pyridiP-4-yl) -l, 2,4-triazolor-4-blpyridazine This compound was prepared using the procedures described in example 16, steps a), b), c), d) and e) except that it was used (l-metñ-l / -l, 2,4-triazol-3-ñ ) methanol (EP-A-421210) instead of 2-pyridine carbinol in step c). Data for the title compound:? NMR (360 MHz, d6-DMSO) d 3.87 (3H, s), 5.56 (2H, s), 7.55-7.65 (3H, m), 7.75-7.77 (2H , m), 8.46-8.50 (3H, m), 8.61 (1H, s), 8.71 (2H, broad d, J = 7 Hz). MS (ES-) m / e 385 [MH] -. Analysis calculated C, 61.66; H, 4.09; N, 28.14. C2oH26N80. 0.05 (H802). 0.3 (H20) requires C, 61.55; H, 4.35; N, 28.43%.

EXAMPLE 121 7-Cyclopepti-6- (l-methyl-l-l, 2,4-triazol-3-ylmethoxy) -3-phenyl-l, 2,4-triazolof4,3-blpiridazine This compound was used as described in example 88, steps a), b) and c), except that (l-metü-li7-l, 2,4-triazol-3-y) methanol was used (EP-A document) -421210) in place of (2-metñ-2 / -rl, 2,4-triazol-3-yn) methanol in step b) and dclopentane carboxy-carboxy was used in place of carboxy-ddohexane carboxy in step c). Data for the title compound: * H NMR (360 MHz, CDCk) d 1.62-1.86 (6H, m), 2.10-2.18 (2H, m), 3.22-3.32 (HH, m), 3.95 (3H, s), 5.57 (2H, s), 7.46-7.57 (3H, m), 7.88 (HH, s), 8.02 ( ÍH, s), 8.50 (2H, broad d, J = 8 Hz). MS (ES-) m / e 376 [MH] -. Analisys calculated C, 63.73; H, 5.56; N, 25.16. C20H21N7O. 0.1 (C4H10O). 0.1 (H2O) requires C, 63.70; H, 5.82; N, 25.59%.

EXAMPLE 122 7-Isopropyl-6- (l-methyl-l-l, 2,4-triazol-3-ylmethoxy) -3-phenyl-l, 2,4-triazoIof4.3-blpiridazipa This compound was prepared as described in example 88 steps a), b) and c), except that (l-metul-l / fl, 2,4-triazol-3-yl) methanol was used (EP-A- 421210) instead of (2-metü-2/7-l, 2,4-triazol-3-ü) methanol in step b) and 2-methypropionic acid was used in place of cyclohexane carboxyHco acid in step c) . Data for the title compound:? NMR (360 MHz, CDCl 3) d 1.31 (6H, d, J = 6.9 Hz), 3.25 (1H, hept, J = 6.7 Hz), 3.94 (3H, s), 5 , 57 (2H, s), 7.46-7.56 (3H, m), 7.86 (HH, s), 8.06 (HH, s), 8.50 (2H, broad d, J = 8 Hz). MS (ES-) m / e 350 [MH] -. Analisys calculated C, 61.86; H, 5.43; N, 27.71. C18H19N7O requires C, 61.88; H, 5.48; N, 28.06%.

EXAMPLE 123 3-Cyclopropyl-6- (l-methyl-lg-l, 2,4-triazol-3-ylmethoxy) -7-fepIl-l, 2,4-triazolof4,3-b1-pyridazipa This compound was prepared using the procedures described in example 2, a), b), c), d), using cidopropyl hydrazide in place of benzoin hydrazine in step c) and using (l-metñ-l fl, 2, 4-triazole-3-y) methanol in place of 2-pyridinecarbinole in step d). aH NMR (360 MHz, CDCls) d 1.14-1.18 (2H, m), 1.36-1.40 (2H, m), 2.42-2.46 (HH, m), 3, 92 (3H, s), 5.55 (2H, s), 7.41-7.45 (3H, m), 7.61-7.64 (2H, m), 7.89 (1H, s) , 8.03 (H, s); MS (ES-) m / e 348 [MH-]. Analisys calculated C, 60.79; H, 4.79; N, 27.33. C18H1 N7O + 0.5% H20 requires C, 60.66; H, 5.09; N, 25.71%.

EXAMPLE 124 3- (2-Fluorophenyl) -6- (2-methyI-2g-1, 2,4-triazol-3-ylmethoxy) -7-fePl-1, 2,4-triazol-4,3-blpyridazine This compound was prepared using the procedures described in the example 2 a), b), c), d), using 2-fluorobenzyl hydrazide in place of benzoyl hydrazine in step c) and using (2-metü-2 / -l, 2,4-triazol-3-ü) methanol instead of 2-pyriducarbinol in step d). 1 H NMR (360MHz, CDCl 3) d 3.89 (3H, s), 5.47 (2H, s), 7.32 (6H, m), 7.65-7.68 (2H,), 7.96 (3H, m); MS (ES-) m / e 402 [MH-]. Calculated Analysis C, 61.85; H, 3.35; N, 23.77. C 21 H 16 N 7 OF + 1% Na requires C, 61.78; H, 3.95; N, 24.01%.

EXAMPLE 125 3- (2-Fluorophenyl) -6- (1-methyl-1-trifluoro-2,4-triazol-3-ylmethoxy) -7-phenyl-1, 2,4-triazolof 4, 3-blpiridazine This compound was prepared using the procedures described in the example 2 a), b), c), d), using 2-fluorobenzyl hydrazide instead of benzoin hydrazine in step c) and using (l-metü-l- ¥ -l, 2,4-triazol-3-ü) methanol in place of 2-? irid? carbinol in step d). ? NMR (360MHz, CDCl 3) d 3.66 (3H, s), 5.53 (2H, s), 7.27 (8H, m), 7.85-7.88 (2H, m), 8.06 (ÍH, s); MS (ES-) m / e 402 [MH-]. Analysis calculated C, 62.49; H, 3.73; N, 23.81. C 21 H 16 N 7 OF + 0.5% Na requires C, 62.48; H, 3.96; N, 24.29%.

EXAMPLE 126 6- (l-MetiI-lg-l, 2,4-triazol-3-ylmethoxy) -7-phepyl-3-thiophen-2-ip-1, 2,4-triazoloyl-4,3-blpiridazine This compound was prepared using the procedures described in example 2 a), b), c) and d), using hydrazide 2-thiophene carboxyHca in place of benzoy hydrazine in step c) and using (l-metfl-177-l, 2,4-triazole-3-ü) methanol (prepared as described in EP-A-421210) in place of 2-pyriducarbinol in step d). ? NMR (360 MHz, CDCk) d 3.91 (3H, s), 5.66 (2H, s), 7.25 (HH, m), 7.43-7.69 (6H, m), 8, 03 (2H, m), 8.31 (1H, m); MS (ES-) m / e 390 [MH] -. Calculated Analysis C, 59.01; H, 3.64; N, 25.10. C19H15N7OS requires C, 58.60; H, 3.88; N, 25.17%.

EXAMPLE 127 6-fl-MetiI-l / -l, 2,4-triazol-3-ylmethoxy) -7-phenyl-3- (pyridin-3-yl) -l, 2,4-triazolof4,3-blpiridazipa This compound was prepared using the procedures described in the example 2 a), b), c), d), using 2-pyridu hydrazide in place of benzoin hydrazine in step c) and using (l-metñ-l -l, 2,4-triazol-3-ü) methanol instead of 2-pyridiccarbinol in step d). ? NMR (360MHz, dd-DMSO) d 3.86 (3H, s), 5.55 (2H, s), 7.49-7.51 (3H, m), 7.64 (1H, m), 7 , 73 (2H, m), 8.44-8.48 (2H, d, J = 14.4Hz), 8.66 (IH, m), 8.82-8.84 (IH, d, J = 7.2 Hz), 9.56 (1H, s); MS (ES-) m / e 385 [MH-]. Analisys calculated C, 62.03; H, 3.97; N, 28.54. C2oH? 6N80 + 0.2% H2O requires C, 61.91; H, 4.26; N, 28.88%.

EXAMPLE 128 6-f2-Methyl-2g-l, 4-triazol-3-ylmethoxy) -7-phenyl-3- (thiophen-2-yl) -1,2,4-triazol-4,3-blpiridazine This compound was prepared using the procedures described in example 2 a), b), c) and d), using hydrazide 2-thiophene carboxyHca in place of benzoy hydrazine in step c) and using (2-metñ-2 / 7- 1, 2,4-triazol-3-yl) methanol (prepared as described in EP-A-21210) in place of 2-pyriducarbinol in step d). ? NMR (360 MHz, CDCls) d 3.79 (3H, .s), 5.74 (2H, s), 7.26 (ÍH, m), ', 47-', 57 (6H, m), 7 , 90 (HH, s), 8.05 (HH, s), 8.24 (HH, m); MS (ES-) m / e 390 [MHJ-. Analysis calculated C, 58.20; H, 4.09; N, 25.02. C19H15N7OS requires C, 58.60; H, 3.88; N, 25.17%.

EXAMPLE 129 6-C2-Methyl-2H-l ^, 4-triazoI-3-ametoxy) -7-phepyl-3- (pyridyl-3-yl) -l, 2,4-triazolof4,3-blpiridazine This compound was prepared using the procedures described in the example 2 a), b), c) and d), using hydrazide 3-pyridine carboxyHca in place of benzoy hydrazine in step c) and using (2-metñ-2 / -l, 2,4-triazol-3-ü) methanol (prepared as described in EP-A-421210) in place of 2-pyriducarbinol in step d). ? NMR (360 MHz, CDCls) d 3.79 (3H, s), 5.69 (2H, s), 7.47-7.57 (6H, m), 7.90 (HI, s), 8, 10 (HH, s), 8.77 (2H, m), 9.76 (HH, s); MS (ES +) m / e 385 [MHJ +. Analisys calculated C, 62.48; H, 4.02; N, 25.56. C2oHi6N80 requires C, 62.49; H, 4.20; N, 29.15%.

EXAMPLE 130 3- (Faran-3-yl) -6- (l-metu-lg-l, 2,4-triazol-3-iL-methoxy) -7-fePiI-l, 2,4-triazolor-4-blpyridazine This compound was prepared using the procedures described in the example 2 a), b), c), d), using 2-furan hydrazide in place of benzoic hydrazine in step c) and using (l-metñ-l / 7-l, 2,4-triazol-3-ü ) methanol instead of 2-pyridine carbinol in step d). ? NMR (360MHz, d6-DMSO) d 3.85 (3H, s), 5.57 (2H, s), 6.84 (HH, m), 7.47 (3H, m), 7.68 (3H , m), 8,01 (ÍH, s), 8,39 (ÍH, s), 8,47 (ÍH, s). MS (ES-) m / e 374 [MH-J. Analysis calculated C, 60.46; H, 4.12; N, 24.14. C19H15N7O2 + 0.1% H2O, 0.1% Na requires C, 60.46; H, 4.06; N, 25.97%.

EXAMPLE 131 6- (l-MetiI-lg-l, 2,4-triazol-3-ylmethoxy) -7-phenyl-3- (thiophen-2-yl) -l, 2,4-triazoium [4,3- b1piridazipa This compound was prepared using the procedures described in the example 2 a), b), c), d), using 2-thiophene hydrazide instead of benzoin hydrazine in step c) and using (l-metü-l- ¥ -l, 2,4-triazol-3-ü ) methanol instead of 2-? iriducarbinol in step d). ? NMR (360MHz, d6-DMSO) d 3.86 (3H, s), 5.60 (2H, s), 7.34 (4H, m), 7.74-7.76 (2H, d, J = 7.2Hz), 7.84-7.86 (1H, d, ./ = 7.2Hz), 8.29 (1H, m), 8.39 (1H, s), 8.48 (1H, s) ). MS (ES-) m / e 390 [MH-]. Calculated analysis C, 58.33; H, 3.50; N, 24.63. C19H15N7OS + 0.1% H2O requires C, 58.33; H, 3.92; N, 25.06%.

EXAMPLE 132 6- (5-Methyl-l, 2,4-oxadiazol-3-ylmethoxy) -3,7-diphenyl-l, 2,4-triazolof4,3-b] pyridazipa This compound was prepared using the procedures described in example 2 a), b), c) and d), using 3-hydroxymeth-5-methylene, 2,4-oxadiazole (J. Med. Chem., 1991, 34 , 1086-94) in place of 2-pyriducarbinol in step d). ? NMR (360 MHz, CDC13) d 2.62 (3H, s), 5.70 (2H, s), 7.50-7.80 (7H, m), 8.45 (2H, m), 8, 48 (ÍH, s); MS (ES-) m / e 385 [MH-]. Analysis calculated C, 65.24; H, 3.94; N, 21.21. C? IHißNeOz. 0.25 H20 requires C, 64.85; H, 4.28; N, 21.61%.

EXAMPLE 133 7-Fepil-3- (thiophen-2-y0-6-f2g-l, 2,4-triazoI-3-H-methoxy) -l, 2,4-triazoIor4,3-blpiridazine This compound was prepared using the procedures described in examples 2 a), b), c), d) and 72 c), using 2-thiophene carboxyHca in place of benzoic hydrazine in step 2c) and using the product of 72a) instead of 2-? iriducarbinol in step 2d). * H NMR (360 MHz, CDCla) d 5.14 (2H, s), 6.72 (HH, m), 6.91 (3H, m), 7.05-7.26 (3H, m), 7.55 (HH, s), 7.76 (2H, m), 13.41 (HH, broad s); MS (ES-) m / e 376 [MH] -. Analysis calculated C, 57.19; H, 2.98; N, 25.61. C18H13 7OS requires C, 57,58; H, 3.49; N, 26.12%.

EXAMPLE 134 3- (Furan-2-yl) -6- (l-methyl-lJ-rl, 2,4-triazol-3-ylmethoxy) -7-fepyl-l, 2,4-triazolof4,3-blpyrid- tzipa This compound was prepared using the procedures described in example 2 a), b), c) and d), using hydrazide 2-furu carboxyHca in place of benzoy hydrazine in step c) and using (l-metü-l / -l , 2,4-triazole-3-Ü) methanol (prepared as described in EP-A-421210) in place of 2-pyriducarbinol in step d). ? NMR (360 MHz, CDCls) d 3.91 (3H, s), 5.63 (2H, s), 6.66 (1H, m), 7.26-7.69 (7H, m), 8, 02 (2H, m); MS (ES-) m / e 374 [MH] -. Analysis calculated C, 60.77; H, 3.93; N, 25.82. C19H15N7O2 requires C, 61.12; H, 4.05; N, 26.26%.

EXAMPLE 135 6-fl-Methyl-lig-l, 2,4-triazol-3-ylmethoxy) -3-phenyl-7- (thiophen-3-yl) -l, 2,4-triazoloí4,3-blpiridazipa This compound was prepared using the procedures described in the example 16 stages a), b) and c) except that 3-thiophene boronic acid was used instead of 4-pyridine. boronic acid, di-HCl salt in step a), 1.1 equivalents of triethylamine hydrochloride were used in step b) in place of 1.1 equivalents of p-toluenesulfonic acid and triethylamine, and (1-methyl) was used. -l / 7-l, 2,4-triazol-3-ü) methanol (example 65) in step c) in place of 2-pyridinecarbinol. Data for the title compound: p.f. 233-235 ° C (MeOH). ? NMR (360 MHz, DMSO) d 3.89 (3H, s), 5.61 (2H, s), 7.56-7.65 (3H, m), 7.71 (1H, dd, J = 5 , 2 Hz), 7.80 (HH, d, J = 5 Hz), 8.29 (HH, d, J = 2 Hz), 8.47 (2H, d, J = 7 Hz), 8.50 (ÍH, s), 8.65 (ÍH, s). MS (ES-) 390 [MH] -. Analisys calculated C, 57.92; H, 3.81; N, 24.79. C19H15N7OS. 0.25 H2O requires C, 57.93; H, 3.97; N, 24.89%.

EXAMPLE 136 6- (2-Methyl-2jy-l, 2,4-triazol-3-ylmethoxy) -7- (thiophen-3-yl) -l, 2,4-triazolor 4,3-blpiridazipa This compound was prepared using the procedures described in example 16 steps a), b) and c) except that 3-thiophene boronic acid was used in place of 4-pyridin boronic acid, di-HTH salt in step a), they used 1.1 equivalents of triethyl amine hydrochloride in step b) instead of 1.1 equivalents of p-toluenesulfonic acid and triethyl amine, and used (2-methy-2l-l, 2,4-triazole-3-yl). ) methanol (example 66) in step c) in place of 2-pyriducarbinol. Data for the title compound: p.f. 220-222 ° C (MeOH). ? NMR (360 MHz, DMSO) d 3.91 (3H, s), 5.79 (2H, s), 7.58-7.65 (3H, rn), 7.71-7.74 (2H, m) ), 8.00 (1H, s), 8.20 (1H, broad s), 8.39 (2H, d,. = 7 Hz), 8.68 (1H, s). MS (ES +) 390 [MH] +. Analysis calculated C, 58.46; H, 3.86. C19H15N7OS requires C, 58.60; H, 3.88%.

EXAMPLE 137 3-Phenyl-7- (thiophen-3-yl) -6- (2 g-l, 2,4-triazol-3-ylmethoxy) -l, 2,4-triazol-4,3-blpiridazine This compound was prepared using the procedures described in the example 16, steps a) and b) and example 72, steps b) and c) except that 3-thiophene boronic acid was used in place of 4-pyridine boronic acid, di-Htium salt in Example 16, Step a) and used 1.1 equivalents of triethylamine hydrochloride in example 16, Step b) instead of 1.1 equivalents of p-toluenesulfonic acid and triethylamine. Data for the title compound: p.f. 264-266 ° C (MeOH). ? NMR (500 MHz, DMSO, 330K) d 5.68 (2H, s), 7.54-7.62 (3H, m), 7.66 (1H, dd J = 5, 2 Hz), 7.77 (HH, d, J = 5 Hz), 8.26 (HH, d, J = 2 Hz), 8.41 (2H, d, J = 7 Hz), 8.50 (HH, broad s), 8 , 58 (ÍH, s). MS (ES-) 376 [MH] -. Analisys calculated C, 56.23; H, 3.28. C18H13N7OS. 0.14 CH2Cl2 requires C, 56.26; H, 3.46%.

EXAMPLE 138 6- (2-Methyl-2g-l, 2,4-triazoI-3-ylmethoxy) -3-phenH-7- (thiofep-2-yl) -l, 2,4-triazolof4 ^ -blpiridazipa This compound was prepared using the procedures described in example 16, steps a), b) and c) except that 2-thiophene boronic acid was used in place of 4-ω-iridobuonic acid, di-Htthio salt in step a) , 1.1 equivalents of triethyl amine hydrochloride were used in step b) instead of 1.1 equivalents of p-toluenesulfonic acid and triethylamine, and (2-methyl-2-yl, 2,4-triazole was used. -3-ü) methanol (example 66) in step c) in place of 2-pyriducarbinol. Data for the title compound: p.f. 250-254 ° C (DMF-H2O). H NMR (360 MHz, d6-DMSO) d 3.96 (3H, s), 5.82 (2H, s), 7.24 (ÍH, dd, J = 5 and 4 Hz), 7.52-7 , 65 (3H, m), 7.80 (HH, d, J = 5 Hz), 8.00 (HH, d, J = 4 Hz), 8.02 (HH, s), 8.42 (2H) , d, J = 7 Hz), 8.80 (ÍH, s). MS (ES-) 390 [MH] -. Analysis calculated C, 58.56; H, 3.93; N, 25.35. C19H15N7OS requires C, 58.60; H, 3.88; N, 25.18%.

EXAMPLE 139 6- (l-Methyl-l-1-l, 2,4-triazol-3-ylmethoxy) -3-phenyl-7-phthiophen-2-yl) -l, 2,4-triazol-4,3-blpiridazine This compound was prepared using the procedures described in example 16, steps a), b) and c) except that 2-thiophene boronic acid was used instead of 4-pyridin boronic acid, di-HTH salt in step a), 1.1 equivalents of triethyl amine hydrochloride were used in step b) in place of 1.1 equivalents of p-toluenesulfonic acid and triethyl amine, and (l-methyl-1-l, 2,4-triazole-3- was used. ñ) methanol (example 65) in step c) in place of 2-pyriducarbinol. Data for the title compound: p.f. 237-239 ° C (DMF-H2O). ? NMR (360 MHz, CDCls) d 3.96 (3H, s), 5.69 (2H, s), 7.14 (HH, dd, J = 6.5 Hz), 7.47 (HH, d, J = 6 Hz), 7.50-7.60 (3H, m), 7.81 (IH, d, J = 5 Hz), 8.08 (IH, s), 8.27 (IH, s) , 8.56 (2H, d, J = 7 Hz). MS (ES-) 390 [MH] -. Analisys calculated C, 57.11; H, 3.96; N, 24.70. C19H15N7OS. 0.5 H20 requires C, 57.27; H, 4.05; N, 24.61%.

EXAMPLE 140 7- (Furan-2-iI) -6- 2-methyl-2? -l, 2,4-triazol-3-ylmethoxy) -3-phenyl-l, 2,4-triazoIof4,3-blpiridazine a) 3,6-Dichloro-4- (furan-2-ü) -pyridazine A mixture of 4-bromo-1,2-dihydropyridazine-3,6-dione was degassed and purged with nitrogen (see example 15 part a) (3.5 g, 18.3 mmol), 2-tributylstannane-furan (6.3 ml, 20 mmol) and bis (triphenphosphine) dichloropalladium (1.42 g, 11 mol%) in dry THF (60 ml ) and then stirred at 70 ° C for 1 hour. After cooling, the mixture was concentrated. The residues were triturated and washed with hexane, then diethyl ether, yielding the crude coupled product as a beige powder (5.23 g) which was used without further purification. The previous solid was mixed with phosphorus oxidide (80 ml) and refluxed for 4 hours. The excess phosphorus oxychloride was removed by evaporation and tilating azeotropically with toluene. The residue was triturated with ice (100 ml) and dichloromethane (200 ml) and neutralized with aqueous sodium bicarbonate (200m). The mixture was filtered and the two phases separated. The organic layer was dried (Na2SQt), filtered and concentrated. Filtration in a short-sice column, eluting with ethyl acetate, gave the title compound as brown crystals (1.67 g, 44% in the two steps). 1 NMR (250 MHz, CDCfe) d 6.67 (ΔI, dd, J = 4, 2 Hz), 7.63 (ΔI, d, J = 4 Hz), 7.71 (ΔI, d, J = 2 Hz), 7.92 (ÍH, s). MS (ES-) 215 and 217 [MHJ-. b) 7- (Furan-2-y) -6- (2-methy-2-yl, 2,4-triazol-3-ylmethoxy) -3-fenfl-l, 2,4-triazolo [4, 3-b]? Iridazine This compound was prepared from 3,6-dichloro-4- (furan-2-ü) -α-iridazine using the procedures described in example 16, steps b) and c), except that they were used 1.1 equivalents of triethyl amine hydrochloride in step b) instead of 1.1 equivalents of p-toluenesulfonics acid and triethyl amine, and was used (2-metü-2ür-l, 2,4-triazol-3-ü) methanol (example 66) in step c) in place of 2-pyriducarbinol. Data for the title compound: p.f. 263-265 ° C (DMF). ? NMR (360 MHz, d6-DMSO) d 3.95 (3H, s), 5.84 (2H, s), 6.74 (HH, dd, J = 4, 2 Hz), 7.21 (HH, d, J = 4 Hz), 7.55-7.65 (3H, m), 8.00 (H, d, J = 2 Hz), 8.03 (H, s), 8.41 (2H, d, J = 7 Hz), 8.47 (1H, s). MS (ES-) 374 [MH] +. Calculated Analysis C, 60.93; H, 4.00; N, 26.09. C19H15N7O2 requires C, 61.12; H, 4.05; N, 26.26%.

EXAMPLE 141 7-0Furan-2-yl) -6-fl-methyI-lg-l, 2,4-triazoi-3-ylmethoxy) -3-phenyl-l, 2,4-triazolof4,3-blpiridazipa This compound was prepared from 3,6-dichloro-4- (furan-2-ü) -pyridazine (Example 140 part a) using the procedures described in Example 16, steps b) and c), except that 1 was used. , 1 equivalent of triethyl amine hydrochloride in step b) instead of 1.1 equivalents of p-toluenesulfonic acid and triethylamine, and (l-met-li-rl, 2,4-triazol-3-yl) methanol (example 65) was used in step c) in place of 2-pyriducarbinol . Data for the title compound: p.f. 257-259 ° C (DMF). ? NMR (360 MHz, d6-DMSO) 3.91 (3H, s), 5.63 (2H, s), 6.74 (HH, dd, J = 4 and 2 Hz), 7.33 (HH, d) , J = 4 Hz), 7.54-7.65 (3H, m), 7.99 (HH, d, J = 2 Hz), 8.44 (HH, s), 8.46 (2H, d) , J = 7 Hz), 8.57 (ÍH, s). MS (ES-) 374 [MH] -. Calculated Analysis C, 60.68; H, 4.11; N, 25.82. C19H15N7O2. 0.15 H2O requires C, 60.68; H, 4.10; N, 26.07%.

EXAMPLE 142 6- (3-Methyl-l, 2,4-oxadiazoI-5-ylmethoxy) -3,7-diphenyl-l, 2,4-triazolo [4,3-b] pyridazine a) 5-Chloromethyl-3-methyl-2,4-oxadiazole. Triethylamine (2.06 ml, 0.015 mol) was added to a solution of acetamide oxime (1 g, 0.0135 mol) in dichloromethane ( 30 ml) and cooled to 0 ° C. Chloro-cetyl chloride (1.18 ml, 0.015 mol) was added dropwise over 5 minutes. The reaction was stirred at 0 ° C for 10 minutes and then at room temperature for 1 hour. The reaction was diluted with dichloromethane (40 ml) and washed with water (2 x 30 ml), brine (1 x 30 ml). The organic layer was dried (MgSO), filtered and evaporated until the crude product was propriogenated. b) 6- (3-Metü-l, 2,4-oxadiazol-5-flmethoxy) -3,7-diene-l, 2,4-triazolo [4,3-b] pyridazine This compound was prepared using the procedures described in the example a) and b) using the product of example 2 c) and the crude product of this example part a). ? NMR (360 MHz, CDCl 3) d 2.35 (3H, s), 5.85 (2H, s), 7.51-7.80 (7H, m), 8.24 (2H, m) 8.48 (ÍH, s); MS (ES-) m / e 385 [MH-]. Analisys calculated C, 65.19; H, 3.99; N, 21.07. C2iHi6N602. 0.05 CH2Cl2 .. 0.1 EtOAc requires C, 64.82; H, 4.29; N, 21.15%.

EXAMPLE 143 3-r4-Fluorophenyl) -6- (l-methyl-lg-l, 2,4-triazol-3-ylmethoxy) -7-phenyl-l, 2,4-triazolo [4,3-bTpyridazipa This compound was prepared using the procedures described in example 2 a), b), c), d), using hydrazide 4-fluorobendHca instead of benzoy hydrazine in step c) and using (l-metü-l / fl, 2,4-triazol-3-y) methanol in place of 2-pyridinecarbinol in step d). p.f. = 233-235 ° C. ? NMR (360MHz, d6-DMSO) d 3.85 (3H, s), 5.52 (2H, s), 7.42 (5H, m), 7.73 (2H, m), 8.40 (H , s), 8.49 (3H, m); MS (ES-) m / e 402 [MH-].

EXAMPLE 144 3,7-Difepil-6- (2 g-l, 2,3-triazol-4-ylmethoxy) -l, 2,4-triazolo [4,3-blpiridazine a) 5-Form-l- [2- (trimethylsilyan) ethoxylmethyl-li-rl, 2,3-triazole A 1.6 M solution of buty-thio in hexanes was added dropwise over 11 minutes 86.70 ml, 10.7 mmol) was added to a stirred solution of l- [2- (trimethylsantane) ethoxy] methyl-1 / -1,2,3-triazole (Holzer, W., Russian,., J. Heterocycl. Chem. , 1992, 29, 1203-7) (2.0344 g, 10.2 mmol) in anhydrous THF (30 ml), cooled to < -75 ° C under nitrogen. The mixture was stirred at this temperature for 30 min and then allowed to warm to -20 ° C for 13 min. The mixture was again cooled to < -75 ° C and anhydrous DMF (0.87 ml, 11.3 mmol) was added dropwise over 8 minutes. The mixture was stirred at < -75 ° C for 1.75 h and then at 0 ° C for 75 min. Saturated aqueous NH Cl (50 mL) was added and the mixture was extracted with diethyl ether (75 mL) and then with ethyl acetate (2 x 75 mL). The organic extracts were dried (Na? SQt) and evaporated under vacuum. The residue was purified by flash chromatography (silica gel, 40% EtOAc / hexane) to provide 1.7256 g (74%) of the title compound as an incolo-ro oil:? NMR (360 MHz, CDCls) d -0.03 (9H, s), 0.91 (2H, m), 3.63 (2H, m), 6.01 (2H, s), 8.28 (H) , s), 10. 08 (ÍH, s); MS (ES-) m / e 170 [M-SiMe2 + HJ- b) 5-Hydroxymethyl-l- [2- (trirnetyl-manganese) ethoxy] nyl-1-yl, 2,3-triazole Sodium borohydride (0.2875 g, 7.60 mmol) was added to a stirred solution of the produced from Step a (1.7204 g, 7.57 mmol) in anhydrous methanol (8 ml), cooled to 0 ° C under nitrogen and the mixture was stirred at this temperature for 20 min and then allowed to warm to room temperature for 30 minutes. The reaction was quenched by adding water and the mixture was partitioned between saturated aqueous NaCl (40 ml) and dichloromethane (30 ml). The aqueous layer was extracted with dichloromethane (3 x 30 ml) and the combined organic extracts were dried (Na ?SOé) and evaporated under vacuum. The residue was purified by flash chromatography (silica gel, 3% MeOH / CH2Cl2) to give 1.4642 g (84%) of the title compound:? NMR (360 MHz, CDCl 3) d -0.02 (9H, s), 0.90 (2H, m), 3.59 (2H, m), 4.82 (2H, s), 5.78 (2H , s), 7.67 (H, s); MS (ES-) m / e 230 [M + H] -, 119. c) 3,7-Different? m-6- [l- [2- (trimetüsüanfl) ethoxy] metü-liy-l, 2,3-triazol-5-y] methoxy-l, 2,4-triazolof 4,3 -b] pyridazine This compound was prepared in a yield of 84% using my simuar procedure to that described in Example 2, Step d, but using 5-hydroxymethyl-1- [2- (trimethylsului) ethoxy] methy-l 1-l, 2,3-triazole (from Step b) in place of 2-pyriducarbinol. Data for the title compound:? NMR (360 MHz, CDCl 3) d -0.07 (9H, s), 0.80 (2H, m), 3.49 (2H, m), 5.62 (2H, s), 5.67 (2H , s), 7.47-7.62 (8H, m), 7.77 (HH, s), 8.39 (HH, s), 8.40 (2H, dd); MS (ES-) m / e 500 [MH] -. d) 3,7-Difenu-6- (2-ir-1, 2,3-triazol-4-methoxy) -l, 2,4-triazolo [4,3-b]? iridazine was stirred at 60 ° C for 5 hours a mixture of the product from Step c (0.7025 g, 1.41 mmol) in ethanol (12 ml) and 2 M aqueous HQ (25 ml). The mixture was then neutralized by adding, dropwise, saturated aqueous Na? COs. The resulting precipitate was collected by filtration, washed with water, then with hexane and dried in vacuo at 60 ° C. This was purified by recrystallized (MeOH-CH? Cl?) and then by flash chromatography (silica gel, 3-5% MeOH / CH2Cl2) to give 0.2044 g (39%) of the title compound as a white solid: m.p. 208-220 ° C; ? NMR (360 MHz,? Fe-DMSO) d 5.66 (2H, s), 7.48-7.49 (3H, m), 7.58-7.72 (5H, m), 7.94 ( ÍH, s wide), 8.40 (HH, s), 8.47 (2H, d, J = 7.2 Hz), 15.10 (HH, broad s); MS (ES-) m / e 370 [MH] -; Analisys calculated C, 65.07; H, 4.05; N, 26.01. C20H15N7O-0, lH2O requires C, 64.72; H, 4.13; N, 26.41%.

EXAMPLE 145 3,7-DifenH-6- (pyrazin-2-ümethoxy) -l, 2,4-triazolol-4,3-b] pyridazipa a) 2-Hydroxymethirazine Diisobutylaluminium hydride (1M solution in THF, 39 ml) was added at -78 ° C with stirring to 2-pyrazinecarboxylate methyl (1.80 g) in THF (60 ml). The solution was allowed to warm to room temperature and stirred for 24 hours. The reaction was quenched with solid tartaric acid and then with aqueous potassium tartrate and stirred for 30 min at room temperature. Aqueous sodium bicarbonate was added until the pH was >; 7. The solution was washed with ethyl acetate (3 x 200 ml), and the combined organic layers were washed with saturated sodium chloride solution (1 x 200 ml), dried (magnesium sulfate) and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, eluent = 5% methanol in dichloromethane), yielding 2-hydroxymethylpyrazine as a dark brown oil (0.16 g). ? NMR (250 MHz, CDCl 3) d 3.42 (HH, broad s), 4.85 (2H, s), 8.55 (2H, m), 8.68 (HH, s); MS (ES-) m / e 111 [MH-]. b) 3,7-Diphenfl-6- (pyrazin-2-ylmethoxy) -l, 2,4-triazolof 4,3-blpiridazine This compound was prepared using the procedures described in the example 2 a), b), c) and d), using 2-hydroxymethylpyrazine instead of 2-? Iridylcarbinol in step d). JH NMR (360 MHz, CDCk) d 5.69 (2H, s), 7.54 (5H, m), 7.65 (2H, m), 8.09 (1H, s), 8.39 (2H, d, J = 6.6 Hz), 8.56 (HH, s), 8.60 (HH, s), 8.67 (HH, s); MS (ES-) m / e 381 [MH-].

EXAMPLE 146 3- (4-Methyphenyl) -6- (l-methyl-l-1-l, 2,4-triazol-3-ylmethoxy) -7-phenyl-l, 2,4-triazoyl-4,3-blpyridazine This compound was prepared using the procedures described in example 2 a), b), c), d), using 4-methanbenzoin hydrazine in place of benzoin hydrazine in step c) and using (l-metñ-l / M, 2,4-triazol-3-ü) methanol in place of 2-pyridinecarbinol in step d). p.f. = 218.6-219.7 ° C. m NMR (360MHz, DMSO) d 2.51 (3H, s), 3.87 (3H, s), 5.54 (2H, s), 7.44 (5H, m), 7.76 (2H, s), 8.38 (4H, m); MS (ES +) m / e 398 [MH-].

EXAMPLE 147 6- (4-Methylthiazol-2-l, methoxy) -3,7-diphenyl-l, 2,4-triazolo [4,3-blpyridazine This compound was prepared using the procedures described in example 2 a), b), c) and d), using 2-hydroxymethyl-4-methythiazole in place of 2- [alpha] - iriducarbinol in step d). Data for the title compound: p.f. = 177 ° C. ? NMR (360 MHz, CDCl 3) d 2.47 (3H, s), 5.79 (2H, s), 6.90 (OH, s), 7.50-7.67 (8H, m), 8, 08 (ÍH, s), 8.50 (2H, d, J = 7.9 Hz); MS (ES-) m / e 400 [MH] -. Analisys calculated C, 66.25; H, 3.90; N, 17.47. C22H17N5OS requires C, 66.14; H, 4.29; N, 17.53%.

EXAMPLE 148 6- (5-Methylthiazol-2-ylmethoxy) -3,7-diphenyl-l, 2,4-triazolof4,3-blpiridazine This compound was prepared using the procedures described in the example 2 a), b), c) and d), using 2-hydroxymethyl-5-methythiazole in place of 2-pyriducarbinol in step d).

Data for the title compound: p.f. = 182 ° C. ? NMR (360 MHz, CDCk) d 2.46 (3H, s), .75 (2H, s), 7.45-7.65 (9H, m), 8.07 (1H, s), 8.49 (2H, d, J = 7.9 Hz); MS (ES-) m / e 400 [MHJ-.

Analysis calculated C, 66.17; H, 4.02; N, 17.67. C22H17N5OS requires C, 66.14; H, 4.29; N, 17.53%.

EXAMPLE 149 3,7-Diphenyl-6- (pyrimidin-4-ylmethoxy) -l, 2,4-triazolof 4, 3-blpiridazipa This compound was prepared using the procedures described in the example 79 a) and b), using 4-doromethypyrimidine (prepared by the procedure of Jeronim et al., Chem. Ber., 1987, 120, 649-651) in place of bromoacetonitride in step b). Data for the title compound:? NMR (360 MHz, CDCl 3) d 5.61 (2H, s), 7.33 (ΔI, d, J = 5.1 Hz), 7.55 (6H, m), 7.67 (2H, m) , 8.10 (HH, s), 8.38 (2H, m), 8.74 (HH, d, J = 5.1 Hz); MS (ES-) m / e 381 [MH-]. Calculated Analysis C, 70.01; H, 3.96; N, 21.97. C 22 H 16 N 6 O requires C, 69.46; H, 4.24; N, 22.09%.

EXAMPLE 150 3,7-Difpil-6-pyridazip-3-ylmethoxy) -l, 2,4-triazolof 4, 3-b] pyridazine This compound was prepared using the procedures described in example 79 a) and b), using 3-chloromethylpyridazine (prepared by the procedure of Jeronim et al., Chem. Ber., 1987, 120, 649-651) in place of bromoacetonitrile in stage b). ? NMR (360 MHz, CDCls) d 5.89 (2H, s), 7.53 (6H, m), 7.64 (2H, m), 8.09 (H, s), 8.40 (2H, m), 9.18 (1H, m); MS (ES-) m / e 381 [MH-].

EXAMPLE 151 6- Methyl-lg-1, 2,4-triazol-3-ylmethoxy) -7- (morpholin-4-yl) -3- (thiophen-2-yn-1, 2,4-triazotor4,3 - blpiridazine a) 4- (3,6-Dichloropyridazin-4-ü) morpholine This was prepared using the procedure described in Example 15 part c) except that morpholine was used in place of piperidine. Data for the title compound: 1 H NMR (250 MHz, CDCls) d 3.30-3.34 (4H, m), 3.87-3.95 (4H, m), 6.89 (1H, s); MS (ES-) m / e 234, 236, 238 [MH-]. b) 6-Chloro-5- (morpholin-4-fl) pyridazin-3-hydrazine A mixture of 4- (3,6-didoropyridazin-4-ü) morpholine (5 g, 21.3 mmol) and hydrate was stirred of hydrazine (7.0 mL, 141 mmol) in 1,4-dioxane (100 mL) and was heated to reflux for 20 hours. After cooling, the 1,4-dioxane was removed in vacuo. The residue was then partitioned between saturated aqueous sodium bicarbonate and dichloromethane. The aqueous layer was extracted again with dichloromethane (x2). The combined organic extracts were dried (Na? SO?), Filtered and evaporated. The residue was purified by chromatography on silica gel, eluting with dichloromethane / methanol / aqueous ammonia (91: 8: 1), yielding 6-chloro-5- (morpholin-4-y) -pyridazin-3-y-hydrazine ( 3.6 g, 74%):? NMR (250 MHz, d6-DMSO) d 3.37-3.17 (4H, m), 3.72-3.77 (4H, m), 4.31 (2H, broad s), 6.58 ( ÍH, s), 7.97 (ÍH, s wide); MS (ES-) m / e 230, 232 [MH-]. c) 6-Chloro-7- (morpholin-4-ü) -2 fl, 2,4-triazolo [4,3-bl? iridazin-3-one) Triphosgene (750 mg, 2.5 mmol) was added to stirring solution of 6-chloro-5- (morpholin-4-ü)? iridazin-3-ü-hydrazine (1.42 g, 6.2 mmol) in 1,2-dichloroethane (60 ml) at room temperature under nitrogen . The mixture was then stirred and heated to reflux for 22 hours. After cooling, the precipitate was collected by flask. The solid was washed with diethyl ether and Then it was dried in vacuo to give 6-doro-7- (morfoHn-4-ü) -2i-rl, 2,4-triazolo [4,3-b] pyridazin-3-one (1.1 g, 67%) which it was used without further purification. Data for the title compound:? NMR (250 MHz, d6-DMSO) d 3.02-3.05 (4H, m), 3.72-3.76 (4H, m), 7.19 (1H, s), 12.57 (1H) , s wide); MS (ES-) m / e 256, 258 [MH-]. d) 3-Bromo-6- (l-metü-lg-l, 2,4-triazol-3-ümethoxy) -7- (morfoUn-4-ñ) -l, 2,4-triazolor4,3-b] pyridazine A mixture of 6-doro-7- (morpholin-4-ü) -2f-1, 2,4-triazolo [4,3-b-pyridazin-3-one (1.1 g, 4.3 mmol) was stirred. and phosphorus bromide (25 g) and heated at 80 ° C for 24 hours. After cooling, the mixture was treated with ice. The aqueous layer was then extracted with dichloromethane (x3). The combined extracts were dried (Na2SO4), filtered and evaporated. The residue was purified by chromatography on silica gel. It eluted with 5% methanol / dichloromethane to give 3-bromo-6-chloro-7- (morpholin-4-ü) -l, 2,4-triazolo [4,3-bjpyridazine] (600 mg). The mass layer and H NMR revealed that the product was a mixture of the desired compound and the 6-bromo compound. This mixture was used without further purification. Sodium hydride (60% dispersion in oil, 80 mg, 2.0 mmol) was added in one portion to a stirred solution of the above product (600 mg) and (1-methyl-1, 2,4-triazole). 3-ü) methanol (240 mg, 2.1 mmol, prepared as described in Example 65) in dry DMF at 0 ° C under nitrogen. The ice bath was removed and the mixture was stirred at room temperature for 2 hours. The reaction was quenched with water and then partitioned between ethyl acetate and water. The aqueous layer was extracted again with dichloromethane (x3). The combined organic extracts were dried (Na2SO4), filtered and evaporated. The residue was purified by chromatography on silica gel, eluting with 5 to 8% methanol / dichloromethane to give the title compound (358 mg, 48% for the 2 steps). 1 H NMR (360 MHz, d 6 -DMSO) d 3.20-3.22 (4H, m), 3.69-3.71 (4H, m), 3.68 (3H, s), 5.47 ( 2H, s), 7.41 (HH, s), 8.49 (HH, s); MS (ES +) m / e 395, 397 [MH-]. e) 6- (l-Metfl-l / -l, 2,4-triazol-3-ümethoxy) -7- (morpholin-4-fl) -3- (thiophen-2-y) -l, 2,4 -triazolo [4,3-bjpiridazine A mixture of 3-bromo-6- (l-methyl-l / 7-l, 2,4-triazol-3-ümethoxy) -7- (morpholin-4-ü) was deoxygenated -l, 2,4-triazolo [4,3-b-pyridazine (100 mg, 0.25 mmol) and 2- (tributylstannane) thiophene (240 mL, 0.75 mmol) in dry DMF (3 mL) bubbling through gaseous nitrogen for 15 minutes. Then didodobis (triphenphosphine) palladium (II) (20 mg) was added. The whole apparatus was then deoxygenated by three "evacuation / filling with N2" dies. The mixture was then stirred at 100 ° C for 16 hours under nitrogen. The reaction mixture was then partitioned between dichloromethane and water. The aqueous layer was extracted again with dichloromethane (x2). The combined extracts were dried (Na2S?), Filtered and evaporated. The residual DMF was removed at high ford. The residue was purified by chromatography on silica gel, eluting with 5% methanol / dichloromethane to provide the title compound (60 mg, 60%). Data for the title compound:? NMR (360 MHz, CDCl 3) d 3.26-3.29 (4H, m), 3.85-3.89 (4H, m), 3.94 (3H, s), 5.64 (2H, s) ), 7.19-7.23 (2H, m), 7.47-7.59 (HH, m), 8.05 (HH, s), 8.18-8.20 (HH, m); MS (ES-) m / e 399 [MH-]. Analysis calculated C, 50.84; H, 4.39; N, 27.35. C17H18N8O2S. 0.3 (H2O) requires C, 50.56; H, 4.64; N, 27.75%.

EXAMPLE 152 3,7-Difpil-6- (thiazol-4-ylmethoxy) -l, 2,4-triazolo [4,3-b.pyridazine This compound was prepared using the procedures described in example 2 a), b), c) and d), using 4-hydroxymeththiathiazole in place of 2-pyridinecarbinol in step d). Data for the title compound: p.f. = 236 ° C. ? NMR (360 MHz, CDCl 3) d 5.73 (2H, s), 7.29 (HH, s), 7.49-7.66 (8H, m), 8.06 (HH, s), 8, 49 (2H, d, J = 7.9 Hz), 8.85 (H, s); MS (ES-) m / e 386 [MHJ-. Analysis calculated C, 65.11; H, 3.72; N, 17.97. C2? H? 5N5OS requires C, 65.44; H, 3.92; N, 18.17%.

EXAMPLE 153 6- (5-Methylisoxazol-3-ylmethoxy) -3,7-diphenyl-l, 2,4-triazolof4,3-blpiridazine This compound was prepared using the procedures described in example 2 a), b), c) and d), using 5-methylisoxazole-3-methanol in place of 2-pyriducarbinol in step d). Data for the title compound: p.f. = 180 ° C. ? NMR (360 MHz, CDCl 3) d 2.42 (3H, s), 5.57 (2H, s), 6.00 (1H, s), 7.49-7.61 (8H, m), 8, 06 (ÍH, s), 8.47 (2H, d, J = 7.9 Hz); MS (ES-) m / e 384 [MH] -. Analisys calculated C, 68.45; H, 4.09; N, 17.79. C22H? 7N5OS, 0, 1H? O requires C, 68.92; H, 4.47; N, 18.27%.

EXAMPLE 154 3- (3-Fluoropheropy) -6- (1-methyl-1-pyr-1, 2,4-triazol-3-ylmethoxy) -7- (morpholin-4-yl) -l, 2,4-triazole-4, 3- pyridazine bl A mixture of 3-bromo-6- (l-methyl-1 / -l, 2,4-triazol-3-umethoxy) -7- (morpholin-4-y) -l, 2,4-triazolo was deoxygenated. 4.3-b] pyridazine (100 mg, 0.25 mmol, from example 151 part d), 3-fluorobenzene boronic acid (50 mg, 0.35 mmol) and anhydrous sodium carbonate (70 mg, 0.66 mmol) in 1,2-dimethoxyethane / water (2: 1, 5 ml) by bubbling nitrogen gas for 15 minutes. Then tetrak? S (triphenphosphine) palladium (0) (30 mg) was added. The entire apparatus was then deoxygenated by three "evacuation / filling with N2" acids. The mixture was then stirred and heated at 110 ° C for 16 hours under nitrogen. After cooling, the mixture was partitioned between dichloromethane and water. The aqueous layer was extracted again with dichloromethane (x2). The combined organic extracts were dried (Na2-5? 4), filtered and evaporated. The residue was purified by chromatography on silica gel, eluting with methanol to % / didoromethane, propranning the title compound (65 mg, 63%). Data for the title compound:? NMR (360 MHz, CDCh) d 3.27-3.29 (4H, m), 3.87-3.90 (4H, m), 3.94 (3H, s), 5.60 (2H, s) ), 7.14-7.19 (HH, m), 7.20 (HH, s), 7.46-7.52 (HH, m), 8.05 (HH, s), 8.21- 8.28 (1H, m); MS (ES-) m / e 411 [MH-]. Analysis calculated C, 53.16; H, 4.85; N, 25.59. CwHwNgOzF. 1.2 (H20) requires C, 52.82; H, 4.99; N, 25.94%.

EXAMPLE 155 3,7-Phenylphenyl-6- (pyrimidin-2-ylmethoxy) -l, 2,4-triazoIof 4,3-blpiridazine a) 2- (Pyrimidin-2-ü) dimethyl malonate Sodium hydride (60% dispersion in mineral oil: 18.9 g) was added, in several portions to dimethyl malonate (41.6 g) in 1.4 -dioxane (900 ml). To the resulting gel was added 2-bromopyrimidine (50.0 g) in 1,4-dioxane (200 ml), in several portions. The mixture was stirred at room temperature for 1 h and then refluxed overnight. To the cooled solution was added water (400 ml) and 5 N hydrochloric acid until the pH was ~ 1. The solution was washed with ethyl acetate (2 x 400 ml), the combined organic phases were washed with a saturated sodium bicarbonate (1 x 400 ml) and saturated sodium chloride solution (1 x 400 ml), dried (magnesium sulfate) and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, eluent = 0 to 20% ethylacetate in dichloromethane), yielding dimethyl 2- (pyrimidin-2-yl) malonate as a yellow-Ho / orange oil ( 24.1 g). ? NMR (250, MHz, CDCfe) d 3.83 (6H, s), 5.16 (HH, s), 7.28 (HH, t, J = 5.0 Hz), 8.87 (2H, d) , J = 5.0 Hz); MS (ES-) m / e 211 [MH-]. b) 2-Metfl? irimidine. Dimethyl 2- (pyrimidin-2-yl) malonate (14.0 g), sodium chloride were heated. (17.1 g) and water (5.24 ml) together in DMSO (50 ml) at 160 ° C overnight. The solution it was allowed to cool and the inorganic material was removed by fütration. The filtrate was distilled at atmospheric pressure and the fraction that bubbled between 95 and 112 ° C was collected. The distillate was distilled again at atmospheric pressure, collecting the fraction that boiled between 97 and 99 ° C - this was a mixture of 2-methypyrimidine and dimethylsulfide, present in a relapse 2: 1 respec- tively (1.41 g). ). This material was used in the next step without further purification. 1 H NMR (250 MHz, CDCls) d 2.70 (3H, s), 7.13 (ΔI, t, J = 4.9 Hz), 8.66 (2H, d, J = 4.9 Hz); MS (ES-) m / e 95 [MH-]. c) 2-Qorometflpyrimidine Trichloroisocyanuronic acid (0.62 g) was added to the product of example 155, Step b) (0.60 g) in refluxing chloroform (30 ml) and the suspension was stirred at reflux for 3 hours. An additional amount of trichloroisocyanuronic acid (0.62 g) was added and the mixture was stirred as above for 6 hours. The suspension was allowed to cool to room temperature, filtered to remove the insoluble material and the filtrate was washed with 1 M sodium hydroxide solution (1 x 25 ml) and saturated sodium chloride solution (1 x 25 ml). The filtrate was dried (magnesium sulfate) and concentrated in vacuo to give 2-chloromethylpyrimidine as a yellow / orange oil (0.11 g). Data for the title compound: 1 H NMR (250 MHz, CDCls) d 4.77 (2H, s), 7.27 (ΔI, t, J = 4.9 Hz), 8.79 (2H, d, J = 4.9 Hz); MS (ES-) m / e 129 [MH-]. d) 3,7-Difenñ-6- (pyrirnidin-2-ümeto? i) -l, 2,4-triazolo [4,3-b] -pyridazine This compound was prepared using the procedures described in the example 79 a) and b), using 2-dorornetylpyrimidine in place of bromoacetonitride in step b). Data for the title compound:? NMR (360 MHz, CDCl 3) d 5.74 (2H, s), 7.23 (1H, t, J = 4.9 Hz), 7.48 (6H, m), 7.81 (2H, m) , 8.06 (H, s), 8.22 (2H, m), 8.76 (2H, d, J = 4.9 Hz); MS (ES-) m / e 381 [MH-]. Analisys calculated C, 69.45; H, 3.81; N, 22.11. C22H? 6N60 requires C, 69.46; H, 4.24; N, 22.09%.

EXAMPLE 156 6- (2-MetiI-2J7-l, 2,3-triazol-4-ylmethoxy) -3,7-diphenyl-l, 2,4-triazolof4,3-b-pyridazine A solution of 3,7-diphen-6- (2/7-l, 2,3-triazol-4-methoxy) -1,4-triazolo [4.3 was added dropwise over 10 minutes. β-pyridazine (from Example 144, Step d) (0.1675 g, 0.453 mmol) in anhydrous DMF (7 ml) to a stirred mixture of sodium hydride (60% dispersion in oil, 22.6 mg, 0.565 mmol) in iodomethane (29.6 ml, 0.475 mmol) in anhydrous DMF, cooled under nitrogen to -5 ° C. The mixture was allowed to warm to room temperature for 2.5 hours and then partitioned between water (40 ml) and ethyl acetate (40 ml). The aqueous layer was extracted again with ethyl acetate (4 x 30 ml), adding saturated aqueous NaCl to allow separation of the phases. The combined organic extracts were dried (Na2S?) And evaporated under vacuum. The residue was purified by flash chromatography (silica gel, 50-100% EtOAc / CH2Cl2), propranning 69.8 mg (40%) of the title compound as a white ssHdo together with 75.8 mg (44%) of a mixture of the analogue 2-methyl-2 -? - 1, 2,3-triazole-4-yne and the analogue l-methyl-1 / -l, 2,3-triazole-5-yl in a 63:37 ratio . Data for the title compound: p.f. 203-205 ° C (CH2Cl2-EtOAc); ? NMR (360 MHz, CDCl 3) d 4.19 (3 H, s), 5.61 (2 H, s), 7.47-7.61 (9 H, m), 8.05 (H, s), 8, 40 (ÍH, s), 8.52 (2H, m); MS (ES-) m / e 384 [MH] -; AnáHsis calcu-side C, 65.27; H, 4.17; N, 25.14. C2? H? 7NtO. 0, lH2O requires C, 65.48; H, 4.50; N, 25.45%.

EXAMPLE 157 7- (l-Methyldclobutyl) -6- (l-methyl-lg-l, 2,4-triazol-3-ylmethoxy) -3-fepyl-l, 2,4-triazolof4,3-blpiridazine This compound was prepared using the procedures described in the example 88 stages a), b) and c) using (l-metñ-l / 7-l, 2,4-triazol-3-ñ) methanol (prepared using the condi- dones described in EP-A-421210) in place of (2-methy-2-Yl, 2,4-triazol-3-ü) methanol in step b) and using carboxy-1-methydodobutane carboxylate (Journal of Organometa -llic Chemistry, 1988, 352, 263-272) in place of dclohexane carboxylic acid in step c). Data for the title compound:? NMR (360 MHz, CDCI3) d 1.56 (3H, s), 1.80-1.91 (HH, m), 2.08-2.24 (3H, m), 2.38-2.52 (2H, m), 3.93 (3H, s), 5.54 (2H, s), 7.46-7.60 (3H, m), 7.69 (IH, s), 8.04 ( ÍH, s), 8.48-8.55 (2H, m); MS (ES-) m / e 376 [MH] -. Analisys calculated C, 64.01; H, 5.51; N, 26.00. C20H21N7O requires C, 63.98; H, 5.64; N, 26.12%.

EXAMPLE 158 7-Isopropyl-6- (2-methyl-2g-l, 2,4-triazol-3-ylmethoxy) -3-fepyl-l, 2,4-triazolo [4,3-blpiridazine This compound was prepared using the procedures described in example 88 steps a), b) and c) using 2-methyropionic acid in place of carboxylic acid cidohexane in step c). Data for the title compound:? NMR (360 MHz, CDCl1) d 1.32 (6H, d, J = 6.8 Hz), 3.10-3.25 (HI, m), 3.98 (3H, s), 5.63 ( 2H, s), 7.47-7.61 (3H, m), 7.91 (IH, d, J = 0.7 Hz), 7.94 (IH, s), 8.32-8.43 (2H, m); MS (ES +) m / e 350 [MH] -. Calculated Analysis C, 62.20; H, 5.28; N, 27.78. QSHWNTO requires C, 61.88; H, 5.48; N, 28.06%.

EXAMPLE 159 7-tert-Butyl-3- (2-fluorofepil) -6- (l-metH-? G-l, 2,4-triazol-3-ylmethoxy) -l, 2,4-triazolof4,3-blpiridazine This compound was prepared using the procedures described in example 102 steps a), b) and c) using trimethylacetic acid in place of carboxy-cidopentane carboxy acid in step a), using 2-fluorobenzoic hydrazide in place of the 2-thiophene carboxy hydrocarid hydrazide. in step b) and using (l-met-l-l-l, 2,4-triazol-3-yl) methanol (prepared using the conditions described in EP-A-421210) instead of 2-hydroxymethylpyridine in stage c). Data for the title compound:? NMR (360 MHz, CDCk) d 1.43 (9H, s), 3.93 (3H, s), 5.44 (2H, s), 7.23-7.37 (2H, m), 7, 48-7.58 (HH, m), 7.94 (HH, s), 7.95-8.00 (HH, m), 8.04 (HH, s); MS (ES-) m / e 382 [MH] -. Calculated Analysis C, 60.20; H, 4.98; N, 25.53. C19H20N7OF requires C, 59.83; H, 5.29; N, 25.71%.

EXAMPLE 160 7-Cyclopeptyl-3- (4-methoxyphenyl) -6-2-methyI-2g-1, 2,4-triazol-3-ylmethoxy) -l, 2,4-triazolof4,3-blpyridazine Prepared in a manner analogous to the procedure described in Example 102b using 4-methoxybenzoic acid hydrazide and Example 102c using (2-methyl-2 / β-l, 2,4-triazol-3-y) methanol, propordinating the compound of the title. ? NMR (250 MHz, CDCl 3) d 1.30 (3H, s), 1.75 (4H, m), 1.88 (4H, m), 3.96 (3H, s), 5.62 (2H, s), 7.53 (3H, m), 7.96 (2H, s), 8.38 (2H, m); MS (ES +) m / e 390 [MH] -.

EXAMPLE 161 7-fl-Methyldclopeptyl) -6- (l-methyl-l / -l, 2,4-triazol-3-ylmethoxy) -3-phenyl-l, 2,4-triazoIof4,3-b1-iridazine Prepared in a manner analogous to the procedure described in Example 102a using 1-methoxy-entanoic acid, Example 102b using benzoic acid hydrazide and Example 102c using (1-methan-1/7-l, 2,4-triazole 3-ü) methanol, propounding the title compound. ? NMR (250 MHz, CDCl 3) d 1.73 (6H, m), 2.08 (2H, m) 3.18 (H, m), 3.90 (3H, s), 3.99 (3H, s) ), 5.62 (2H, s), 7.06 (3H, m), 7.88 (IH, d, J = 1.1Hz), 7.95 (IH, s), 8.36 (2H, m); MS (ES-) m / e 406 [MH] -.

EXAMPLE 162 7- (1-Methoxypeatyl) -6- (2-methyl-2Jy-1, 2,4-triazol-3-ylmethoxy) -3-phenyl-1, 2,4-triazolo [4,3-b1-pyridazine Prepared in a manner analogous to the procedure described in Example 102a using acid-methyldopentanoic acid, example 102b using benzoic acid hydrazide and example 102c using (2-methy-2 / fl, 2,4-triazole-3-yl) methanol , providing the title compound,? NMR (250 MHz, CDCk) d 1.35 (3H, s), 1.64 (4H, m), 1.72 (4H, m), 3.94 (3H, s), 5.57 (2H, s), 7.52 (3H, m), 7.91 (HH, s), 8.06 (HH, s), 8.49 (2H, m); MS (ES-) m / e 390 [MH] -.

EXAMPLE 163 7-Cidopentyl-3- (furan-2-yl) -6- (2-methyl-2g-l, 2,4-triazol-3-ylmethoxy) -l, 2,4-triazolof4,3-blpiridazine It was prepared analogously to the procedure described in example 102b using 2-furoic acid hydrazide and example 102c using (2-methyl-2-flu-1, 2,4-triazl-3-y) methanol to provide the title compound . ? NMR (250 MHz, CDCls) d 1.72 (6H, m), 2.08 (2H, m), 3.19 (H, m), 4.04 (3H, s), 5.67 (2H, s), 6.64 (HH, m), 7.42 (HH, d, J = 3.5Hz), 7.68 (HH, d, J = 1.6Hz), 7.86 (HH, d, J = 1Hz), 7.95 (HH, s); MS (ES-) m / e 365 [MH] -.

EXAMPLE 164 7-Cidopentyl-3-ffuran-2-yl) -6- (l-methyl-lg-l, 2,4-triazol-3-ylmethoxy) -l, 2,4-triazolof4,3-blpiridazine It was prepared analogously to the procedure described in example 102b using furoic acid hydrazide and example 102c using (l-met-l-f-l, 2,4-triazol-3-yl) methanol to provide the title compound. H NMR (250 MHz, CDCl 3) d 1.74 (6H, m), 2.13 (2H, m), 3.26 (1H, m), 3.95 (3H, s), 5.59 (2H , s), 6.64 (HH, m), 7.55 (HH, d, J = 3.5 Hz), 7.66 (HH, d, J = 1.4 Hz), 7.83 (HH) , d, J = 1.1 Hz), 8.06 (H, s); MS (ES-) m / e 365 [MH] - EXAMPLE 165 3-f3,7-Diphenyl-l, 2,4-triazolof4,3-blpiridazip-6-yloxymethyl) -l, 2,4-triazol-1-ylketoPytril The product of example 72, Step c) (0.10 g) in DMF (5 ml) was suspended. Sodium hydride (15 mg of a 60% dispersion in mineral oil) was added and the mixture was stirred at room temperature for 15 minutes. Chloroacetonitrile (41 μl) was added and the mixture was stirred as above for 2 days. Water (25 ml) was added and the resulting precipitate was separated by fütradón and purified by flash chromatography (silica gel, 0 to 3% methanol in dichloromethane). The product was recrystallized from ethyl acetate / ethanol, propranning colorless crystals (17 mg). ? NMR (360 MHz, d6-DMSO) d 5.60 (2H, s), 5.61 (2H, m), 7.48 (6H, m), 7.76 (2H, m), 8.41 (2H, s), ÍH, s), 8,44 (2H, m), 8,68 (ÍH, s); MS (ES-) m / e 409 [MH-]. Analisys calculated C, 64.62; H, 3.74; N, 26.82. CnHuNsO. 0.1 H802 requires C, 64.62; H, 4.06; N, 26.87%.

EXAMPLE 166 7-Cl-Methydopropyl) -6- (2-methyl-2jy-l, 2,4-triazol-3-ylmethoxy) -3-phetyl-l, 2,4-triazolor-4-blpyridazine It was prepared analogously to the procedure described in example 102a using 1-methylated acid-ropanoic acid, example 102b using benzoic acid hydrazide and example 102c using (2-methan-2H-1, 2,4-triazole-3-). ñ) methanol, providing the title compound. ? NMR (360 MHz, CDCla) d 0.79-0.88 (4H, m), 1.37 (3H, s), 4.02 (3H, s), 5.67 (2H, s), 7, 51-7.58 (3H, m), 7.94 (2H, d, J = 4.8 Hz), 8.38 (2H, d, J = 6.6 Hz); MS (ES-) m / e 362 [MH-].

EXAMPLE 167 7-fl-Methyl-cycloprop U) -6- (l-methyI-lg-l, 2,4-triazol-3-Umethoxy) -3-phenyl-l, 2,4-triazolol-4,3-blpiridazine Prepared analogously to the procedure described in example 102a using 1-methydopropanoic acid, example 102b using benzoic acid hydrazide and example 102c using (l-meth-l-1, 2,4-triazole-3-y) methanol, propounding the title compound. iH NMR (360 MHz, CDCls) d 0.78-0.90 (4H, m), 1.42 (3H, s), 3.94 (3H, s), 5.60 (2H, s), 7 , 46-7.58 (3H, m), 7.87 (H, s), 8.05 (ÍH, s), 8.49 (2H, d, J = 6.6Hz); MS (ES-) m / e 362 [MH-].

EXAMPLE 168 3- (3-Fluorophenip-6- (l-methyl-ljy-l, 2,4-triazol-3-ylmethoxy) -7-fepyl-l, 2,4-triazoIof4,3-blpiridazipa This compound was prepared using the procedures described in example 2 a), b), c), d), using 3-fluorobenzyl hydrazide in place of benzoic hydrazine in step c) and using (l-metü-li7-l, 2,4-triazol-3-ü) methanol in place of 2-pyriducarbinol in step d). Data for the title compound: p.f. = 250-251 ° C. ? NMR (360 MHz, d6-DMSO) d 3.55 (3H, s), 5.25 (2H, s), 7.36 (3H, m), 7.42 (3H, m), 7.95 ( HH, d, J = 7.2 Hz), 7.98 (HH, d, J = 7.2 Hz), 8.12 (HH, s), 8.17 (HH, s); (ES-) m / e 402 [MH-]. Analysis calculated C, 61.66; H, 3.87; N, 23.29. C21H16N7OF + 0.5% H2O + 0.1% EtOAc requires C, 61.64; H, 4.16; N, 23.51%.

EXAMPLE 169 7- (1-Methylcienpeptyl) -6- (3-methy1-pyridip-2-ylmethoxy) -3-phetyl-l, 2,4-triazolof4,3-blpiridazip 2-Hydroxymethylene-3-methyl-iridine (43 mg) was dissolved in dimethylformamide (2 ml) under N2. Sodium hydride (60% w / w in oil 14 mg) was added, followed after 5-10 minutes by 6-chloro-7- (l-metü-cidopentin) -3-phene-1, 2,4-triazolo [ 4,3-b] pyridazine (100 mg). The reaction was stirred at room temperature for 18 hours, partitioned between ethyl acetate and water, the organic phase was separated, dried (MgSO 4) and evaporated to dryness. Recrystallization from ethyl acetate gave the pure product. 1K NMR (360 MHz, COCk) d 1.30 (3H, s), 1.77 (6H, m), 1.93 (2H, m), 2.44 (3H, s), 5.62 (2H , s), 7.25 (HH, m), 7.50 (3H, m), 7.58 (HH, d, J = 7.8 Hz), 7.92 (HH, s), 8.42 (2H, d, J = 6.4 Hz), 8.50 (HH, m), ms (ES-) m / e 400 [MH] -.

EXAMPLE 170 6-d-Methyl-l-- -l, 2,3-triazol-4-ylmethoxy) -3,7-diphenyl-l, 2,4-triazoIof4,3-blpiridazipa The mixture of the title compound and the analog 2-methan-2-flu-1, 2,3-triazole-4-yu (from Example 156) was separated by preparative HPLC using a KR100-SC18 column (250 x 4.6 mm) ), eluting with 35% MeCN / 0.1% aqueous TFA to ml / min. The fractions containing the isomer that elutes more slowly were combined and evaporated under vacuum. The residue was partitioned between NaHCO? saturated aqueous (30 ml) and dichloromethane (15 ml). The aqueous layer was extracted again with dichloromethane (2 x 15 ml), and the combined organic extracts were dried (Na 2 SO 3) and evaporated under vacuum. The residue was recrystallized from CH2Cl2-E-OAC-hexane, affording the title compound as a white solid with a purity of > 95% by HPLC; ? NMR (360 MHz, CDCl 3) d 4.05 (3 H, s), 5.67 (2 H, s), 7.46-7.62 (9 H, m), 8.04 (H, s), 8, 51 (2H, m); MS (ES) EXAMPLE 171 3-f5-Methylthiophen-2-yl) -6-l-methyI-lg-1, 2,4-triazol-3-ylmethoxy) -7-phetyl-l, 2,4-triazolo [4,3- blpiridazine This compound was prepared using the procedures described in the example 2 a), b), c), d), using 5-methynthrophene hydrazide in place of benzoic hydrazine in step c) and using (l-methyl-1, 2,4-triazole-3-yl) methanol instead of 2-pyriducarbinol in step d). p.f. = 209-210 ° C. ? NMR (360 MHz, d6-DMSO) d 2.37 (3H, s), 3.66 (3H, s), 5.37 (2H, s), 6.83-6.84 (HH, d, J = 3.6 Hz), 7.28 (3H, m), 7.52 (2H, m), 7.88-7.89 (HH, d, J = 3.6 Hz) 8,17 (ÍH, s), 8,28 (1H, s); MS (ES-) m / e 404 [MH-J.

EXAMPLE 172 2-r3- (3,7-Differential, 2,4-triazolof4,3-blpyridazi P-6-yloxymethyl) -l, 2,4-triazol-1-yl-1-α-V-dimethylacetamide This compound was prepared using the procedure described in Example 165, using 2-chloroacetonide, instead of chloroacetonitrone. ? NMR (360 MHz, CDCls) d 2.99 (3H, s), 3.07 (3H, s), 4.99 (2H, s), 5.62 (2H, s), 7.50 (6H, m), 8.04 (HH, s), 8.24 (HH, s), 8.54 (2H, m); MS (ES-) m / e 455 [MH-J. Anahsis found C, 62.83; H, 4.46; N, 24.31. C24H22N8O2. 0.25 H2O requires C, 62.80; H, 4.94; N, 24.41%.

EXAMPLE 173 3,7-Diphenyl-6-yl- (pyridin-2-ylmethyl) -lt-1, 2,4-triazol-3-yl-ethoxyl-l, 2,4-triazolof 4, 3-blpiridazine This compound was prepared using the procedure described in the example 165, using 2-picoHlo chloride instead of chloroacetonitrile. X H NMR (360 MHz, CDCl 3) d 5.42 (2 H, s), 5.63 (2 H, s), 7.08 (H, d, J = 7.8 Hz), 7.21 (H, m) ), 7.51 (7H, m), 7.68 (2H, m), 8.03 (HH, s), 8.24 (HH, s), 8.51 (3H, m); MS (ES-) m / e 461 [MH-]. Anahsis found C, 67.23; H, 4.22; N, 23.75. C26H2oN80. 0.1 H802 requires C, 67.57; H, 4.47; N, 23.88%.

EXAMPLE 174 6- (l-Bepcyl-lJg-l, 2,4-triazoI-3-ylmethoxy) -3,7-diphenyl-l, 2,4-triazolof4,3-blpiridazine This compound was prepared using the procedure described in Example 165, using benzine bromide in place of chloroacetonitrile. aH NMR (360 MHz, CDCl 3) d 5.30 (2H, s), 5.62 (2H, s), 7.22 (2H, m), 7.33 (3H, m), 7.50 (6H , m), 7.68 (2H, m), 8.03 (HH, s), 8.04 (HH, s), 8.53 (2H, m); MS (ES-) m / e 460 [MH-]. Anahsis found C, 70.40; H, 4.20; N, 21.40. C27H21N7O requires C, 70.57; H, 4.61; N, 21.34%.

EXAMPLE 175 2-y5- 3,7-Diphenyl-l, 2,4-triazoIof 4,3-blpyridazin-6-yloxymethyl) -1,4-triazole-1-yllacetamide This compound was prepared using the procedure described in Example 165, using iodoacetamide instead of chloroacetonitrile. ? NMR (400 MHz, CDCl 3 + dβ-DMSO) d 4.82 (2H, s), 5.74 (2H, s), 6.55 (HH, broad s), 7.18 (HH, broad s), 7.54 (8H, m), 7.90 (HH, s), 8.06 (HH, s), 8.39 (2H, m); MS (ES-) m / e 427 [MH + J.

EXAMPLE 176 iV-f2-r3- (3,7-Difpil-l, 2,4-triazolo [4.3-blpyridazin-6-yloxymethyl) -l, 2,4-triazol-1-yl-inein-? V- dimethylamine The product of example 72, Step c) (0.10 g) was suspended in THF (5 ml). Triphenylphosphine (71 mg), γ-dimethetanolamine (30 μl) and diethyl azodicarboxate (43 μl) were added and the mixture was stirred at room temperature for 24 hours. Additional triphenylphosphine (71 mg) and diethylazodicarboxylate (43 μl) were added and the mixture was stirred as above for 24 hours. Water (50 ml) was added and the resulting solution was added (pH ~ 1) with doric acid.

N solution. The solution was washed with dichloromethane (3 x 25 ml), basified with sodium hydroxide. 4 N (pH ~ 14), and extracted again with dichloromethane (3 x 25 ml). The organic layers of the second extract were combined, dried (magnesium sulfate) and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, 0 to 9% methanol in dichloromethane) and recrystallized from ethyl acetate / hexane, proprating colorless crystals (33 mg). * H NMR (360 MHz, CDCl 3) d 2.22 (6H, s), 2.70 (2H, t, J = 6.2 Hz), 4.21 (2H, t, J = 6.2 Hz) , 5.61 (2H, s), 7.52 (6H, m), 8.04 (HH, s), 8.16 (HH, s), 8.55 (2H, m); MS (ES-) m / e 441 [MH-]. Analysis found C, 64.97; H, 5.22; N, 25.06. C 24 H 2 N 8 O requires C, 65.44; H, 5.49; N, 25.44%.

EXAMPLE 177 3,7-Diphenyl-6- (pyrimidin-5-methoxy) -l, 2,4-triazolof 4, 3-blpiridazine a) 5-Bromomethypyrimidine They were heated together at reflux in carbon tetraeloride (480 ml) 5-methypyrimidine (3.0 g),? -bromosuccinimide (7.1 g) and benzoyl peroxide (63 mg), irradiating with a 60 W bulb for 2 h. The suspension was allowed to cool to room temperature and filtered off. The filtrate was washed with 10% sodium bicarbonate solution (2 x 250 ml), dried (magnesium sulfate) and concentrated in various amounts to give an orange solid - this was a mixture of 5-bromomethy? Irimidine and 5-dibromomethypyrimidine , present in a 3: 2 ratio, respectively (4.2 g). This material was used in the next step without further purification. ? NMR (250 MHz, d6-DMSO) d 4.98 (2H, s), 9.30 (2H, s), 9.43 (1H, s); MS (ES-) m / e 172, 174 (ratio 1: 1) [MH-]. b) 3,7-Difer? fl-6- (pyrimidin-5-ylmethoxy) -l, 2,4-triazolo [4,3-blpiridazine] This compound was prepared using the procedures described in the example 79 a) and b), using 5-bromomethypyrimidine in place of bromoacetonitride in step b). ? NMR (360 MHz, CDCls) d 5.56 (2H, s), 7.56 (8H, m), 8.07 (ÍH, s), 8.38 (2H, m), 8.82 (2H, s), 9.22 (1H, s); MS (ES-) m / e 381 [MH + J.

EXAMPLE 178 6-fl-f2-fMorpholin-4-yl) -ethyl) -lg-1, 2,4-triazol-3-ylmeth? -i1-3,7-diphenyl-l, 2,4-triazolof4, 3-blpiridazipa This compound was prepared using the procedure described in the example 176, using 4- (2-hydroxyethyl) morpholine in place of α and V-dimetwethanolamine. aH NMR (400 MHz, CDCls) d 2.41 (4H, t, J = 4.6 Hz), 2.75 (2H, t, J = 6.2 Hz), 3.63 (4H, t, J = 4.6 Hz), 4.23 (2H, t, J = 6.2 Hz), 5.61 (2H, s), 7.51 (6H, m), 7.69 (2H, m), 8.05 (H, s), 8 , 17 (ÍH, s), 8.55 (2H, m); MS (ES +) m / e 483 [MH-J.

EXAMPLE 179 6- (2-Methyl-2g-l, 2,4-triazoI-3-ylmethoxy) -3-phenyl-7- (pyrrolidin-1-yl) -l, 2,4-triazol-4,3-b1-pyridazine a) 6-Clor o-3-f enü-7- (pyrr or Hdin-1-fl) -l, 2,4-triazolo [4,3-b] pyridazine This compound was prepared using the procedures described in example 15 , steps a, b, c, d using pyrroHdine in step c. b) 6- (2-Methan-2-l, 2,4-triazol-3-methoxy) -3-phene-7- (pyrroHdin-1-fl) -l, 2,4-triazolo [4,3- bjpiridazine Sodium hydride (60% dispersion in oil, 20 mg, 0.36 mmol) was added to a solution of 6-doro-3-phene-7 - (? irroHdin-l-ü) -l, 2,4- triazolo [4,3-b] pyridazine (100 mg, 0.33 mmol) and 3-hydroxymethyl-2-methyl-2,4-triazole in dry DMF (5 ml). The mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with water (50 ml) and extracted with didoromethane (3 x 25 ml). The combined extracts were washed with brine, dried over magnesium sulfate, filtered and evaporated. The solid was triturated with methanol and collected by fumigation, yielding the title pyridazine (68 mg, 55%). aH NMR (360 MHz, CDCls) d 1.93-1.97 (4H, m), 3.41-3.45 (4H, m), 4.00 (3H, s), 5.58 (2H, s), 6.66 (HH, s), 7.43-7.53 (3H, m), 7.94 (HH, s), 8.28 (2H, d, J = 8.3 Hz). MS (ES +) 377 [MH] -.

EXAMPLE 180 7- (5-Chlorothiophen-2-yl) -6-f2-methyl-2g-l, 2,4-triazol-3-ylmethoxy) -3-phenyl-l, 2,4-triazoIoF4,3-blpiridazine This compound was prepared using the procedures described in the example 16 steps a), b) and c) except that 5-chloro-2-thiophene boronic acid was used in place of 4-pyridin boronic acid, di-Htlium salt in step a), 1.1 equivalents of hydrochloride were used of triethynamine in step b) instead of 1.1 equivalents of acid / j-toluenesulfonic acid and triethyl amine and 3-hydroxymethyl-2-methylene, 2,4-triazole (example 65) was used in step c) in place of 2-pyridincarbinol. Data for the title compound: p.f. 244-247 ° C (EtOAc). 1 H NMR (360 MHz, d 6 -DMSO) d 3.95 (3 H, s), 5.82 (2 H, s), 7.30 (H, d, J = 4 Hz), 7.55-7.65 (3H, m), 7.93 (HH, d, J = 4 Hz), 8.03 (HH, s), 8.41 (2H, d, J = 7 Hz), 8.88 (HH, s) ). MS (ES-) 424 [MH] -. Calculated Analysis C, 53.01; H, 3.37. C19H14N7CIOS. 0.35H2O requires C, 53.05; H, 3.44%.

EXAMPLE 181 7-f5-Chlorothiophen-2-yl) -6- (1-methyl-1-l, 2,4-triazol-3-ylmethoxy) -3-phenyl-1, 2,4-triazolo [4,3 -blpiridazine This compound was prepared using the procedures described in example 16 steps a), b) and c) except that 5-chloro-2-thiophene boronic acid was used in place of 4-pyridin boronic acid, di-HTH salt in the step a), 1.1 equivalents of triethylamine hydrochloride were used in step b) instead of 1.1 equivalents of acid / xuenesulfonic and triethylene and 3-hydroxymethylene-1-methane, 2,4-triazole (example 65) was used in step c) in place of 2-pyriducarbinol. Data for the title compound: p.f. 248-250 ° C (EtOAc). ? NMR (360 MHz, dd-DMSO) d 3.89 (3H, s), 5.64 (2H, s), 7.29 (ΔI, d, J = 4 Hz), 7.56-7.62 ( 3H, m), 7.93 (H, d, J = 4 Hz), 8.45 (2H, d, J = 7 Hz), 8.54 (H, s), 8.83 (H, s) . MS (ES-) 424 [MH] -. Analisys calculated C, 53.56; H, 3.36. C19H14N7CIOS. 0, lH2O requires C, 53.61; H, 3.36%.

EXAMPLE 182 6- (lg-Benzimidazol-2-ylmethoxy) -3- (2,4-difluoropropyI) -7-fl-methylcyclide-pentyl) -1,4-triazoIof4,3-bl pyridazine 2- (Hydroxymethyl) benzimidazole (39 mg) was dissolved in dimethylformamide (2 ml) under N2. Sodium hydride (60% w / w in oil, 11 mg) was added, followed, after 5-10 minutes by 6-chloro-7- (l-metü-cyclopentin) -3-phenol, 2,4- triazolo [3,4-b] pyridazine (80 mg). The reaction was stirred at room temperature for 18 hours, partitioned between ethyl acetate and water, the organic phase was separated, dried (MgSO 4) and evaporated to dryness. Chromatography on silica eluting with ethyl acetate gave the pure product. 1 H NMR (500 MHz, CDCls) d 1.33 (3 H, s), 1.67 (4 H, m), 1.80 (2 H, m), 1.93 (2 H, m), 5.69 (2 H , s), 7.04 (HH, m), 7.13 (HH, m), 7.31 (2H, m), 7.40 (HH,), 7.79 (HH, m), 7, 88 (1H, m), 7.96 (1H, s); ms (ES-) m / e 461 [MH] -.

EXAMPLE 183 3-fFurap-3-yl) -6-f2-pyridyl) methyloxy-7,8,9,10-tetrahydro-l, 2,4-triazolof3,4-alftalazine a) 2,3,5,6,7,8-Hexahydrophthalazine-1,4-dione. 3,4,5,6-Tetrahydrophthalic anhydride (25 g, 0.164 mol) was dissolved in 40% aqueous acetic acid (500 ml. ) with sodium acetate trihydrate (26.8 g, 0.197 mol) and hydrate drazine (9.58 ml, 0.197 mol). The reaction mixture was heated to reflux overnight and then allowed to cool, the resulting solid was collected by flushing, washed with water and diethyl ether and dried in vacuo, by coupling the title product (23 g, 84%),? NMR (250 MHz, dVDMSO) d 1.64 (4H, broad s, 2 of CH2), 2.34 (4H, broad s, 2 of CH2), 11.30 (2H, broad s, 2 of NH); MS (ES-) m / e 167 [MH] -. b) 1, 4-Didoo-5,6,7,8-tetrahydrophthalazine The above dione (23 g, 0.14 mol) was dissolved in phosphorus oxychloride (200 ml) and heated to reflux overnight. The solvent was evaporated in vacuo and azeotroped with toluene. The residue was dissolved in dichloromethane (200 ml), stirred rapidly and saturated sodium bicarbonate solution (200 ml) was slowly added. Sodium bicarbonate was carefully added until the effervescence ceased and the mixture was then partitioned between dichloromethane and water. The organic layer was separated, dried (MgSO 4) and evaporated in vacuo. The residue was triturated with diethyl ether and dried under vacuum, yielding the title product (25.8 g, 92%),? NMR (250MHz, CDCls) d 1.84-1.90 (4H, m, 2 CH2), 2.72-2.78 (4H, m, 2 CH2). c) l-Chloro-4-hydrazino-5,6,7,8-tetrahydrophthalazine A mixture of the above product (18.3 g, 0.090 mol) and hydrazine monohydrate (13.6 ml) was refluxed overnight. , 0.28 mol) in ethanol (280 ml). The mixture was cooled to room temperature and the resulting precipitate was filtered off. The filtrate was evaporated under vacuum, yielding the title product (14.86 g, 83%),? NMR (250MHz, CDCls / dß-DMSO) d 1.79-1.92 (4H, m, 2 of CH2), 2.59-2.65 (2H, m, CH2), 2.73-2.78 (2H, m, CH2). d) 6-Aoro-3 ^ (furan-3-fl) -7,8,9,10-tetrahydro-l, 2,4-tiazolor-3,4-alftalazine l, 1-carbonadimidazole (0.98 g) was added. 6.1 mmol) was added to a stirred mixture of 3-furoic acid (0.68 g, 6.1 mmol) in THF (30 mL). The mixture was stirred for 0.75 h before adding the above hydrazine (1.0 g, 5.1 mmol). After 4 hours at room temperature, the solvent was evaporated in vacuo, water was added and the mixture was stirred for 0.5 hour. The resulting solid was collected by fumigation, washed with water and hexane and dried under vacuum, and the ketohydrazine was introduced. A mixture of ketohi-drazine (0.80 g) and triethyl amine hydrochloride (0.10 g, 0.73 mmol) in xylene (10 ml) was heated at reflux overnight. The solution was cooled to room temperature and the solvent was removed under vacuum. The residue was chromatographed on a silica gel, eluting with 5% methanol / dichloromethane to give the title phthalazine (0.21 g),? NMR (250MHz, CDCls) d 1.90-2.02 (4H, m, 2 of CH2), 2.74-2.80 (2H, m, CH2), 3.16-3.24 (2H, m , CH2), 7.28 (HH, m, Ar-H), 7.58 (HH, t, J = 1, 7Hz, Ar-H), 8.53 (HH, m, Ar-H). e) 3- (Furan-3-fl) -6- (2-pyridu) methyloxy-7,8,9,10-tetrahydro-l, 2,4-triazolof3,4-a] phthalazine Sodium hydride (55) was added. mg of a 60% dispersion in oil, 1.4 mmol) was added to a solution of 2-pyridylcarbinol (160 mg, 1.46 mmol) in DMF (10 ml) and the mixture was stirred at room temperature for 0.5 h. After this time, the above product (100 mg, 0.365 mmol) was added and the reaction mixture was stirred at room temperature for 3 h before it was poured into water. The mixture was extracted with ethyl acetate (x3) and the combined extracts were washed with water (xl) and brine (xl), dried (Na2SO4) and evaporated under vacuum. The resulting solid was washed with ethyl acetate, propranning the title compound,? NMR (250MHz, CDCls) d 1.92-2.02 (4H, m, 2 of CH2), 2.72-2.78 (2H, m, CH2), 3.12-3.16 (2H, m , CH2), 5.60 (2H, s, CH2), 7.24 (H, m, Ar-H), 7.31 (H, m, Ar-H), 7.51-7.57 (2H , m, Ar-H), 7.79 (HH, m, Ar-H), 8.44 (HH, m, Ar-H), 8.64 (HH, m, Ar-H); MS (ES-) m / e 348 [MH] -; Calculated Analysis C, 62.84; H, 4.98; N, 18.99. C19H17N5O2. 0.9H2O requires C, 62.77; H, 5.21; N, 19.26%.

EXAMPLE 184 7-Cyclobutyl-3-phenyl-6- (prop-2-ynyloxy) -l, 2,4-triazolof4,3-b] pyridazipa A suspension of 60% sodium hydride in oil (31 mg, 0.77 mmol) was added to a stirred solution of propargue alcohol (47 mg, 0.84 mmol) in DMF (2 mL). The mixture was allowed to stir for 5 minutes before adding 6-doro-7-d-butbutyl-3-phenyl-2,4-triazolo [4,3-b-pyridazine (200 mg, 0.70 mmol). It was allowed to stir for 90 minutes. It was quenched (H ?O), extracted (ethyl acetate), washed (H 2 O, brine), dried (MgSO *) and evaporated in vacuo. The residue was purified by chromatography on silica gel using 50/50 ethyl acetate / hexane as eluent. The title compound was obtained as a white solid. ? NMR (250 MHz, CDCls) d 2.19-2.26 (HH, m), 2.37-2.55 (3H, m), 2.69-2.80 (2H, m), 2.90 (HH, m), 3.97 (HH, m), 5.35 (2H, d, J = 2.4 Hz), 7.77-7.89 (3H, m), 8.13 (HH, s), 8.80 (ÍH, s), 8.86 (ÍH, s). Mass Storm ES- (M + l) = 305.

EXAMPLE 185 (7-Cidobutyl-3-phenyl-l, 2,4-triazolo [4,3-b] pyridaziP-6-yloxy) acetonitrile a) 7-Cyclobutfl-3-phene-l, 2,4-triazolo [4,3-b]? iridazm-6-one. Heated to reflux for 16 hours 6-doro-7-cidobutu-3-phene-1 , 2,4-triazolo [4,3-b-pyridazine (2.0 g, 7.0 mmol), 2N NaOH (50 mL) and 1,4-dioxane (10 mL). It was cooled and water (150 ml) was added. The precipitate was filtered and suspended in H2O, acidified (2 N HCl), filtered off and dried, and a white solid was added. ? NMR (250 MHz, CDCls) d 1.89-2.02 (HH, m), 2.08-2.25 (3H, m), 2.36-2.48 (HH, m), 3.56 -3.70 (HH, m), 7.48-7.60 (3H, m), 7.88 (HH, s), 8.38 (HH, m). Mass spectrum ES- (M + l) = 267. b) (7-Cyclobutyl-3-ferul-l, 2,4-triazolo [4,3-bJ? iridazin-6-ñonoxy) -acetonitrile The above product (300 mg, 1%) was stirred together in DMF for 90 minutes. 13 mmol), bromoacetonitrile (200 mg, 1.69 mmol) and 60% sodium hydride suspension in oil (54 mg, 1.35 mmol). It was quenched (H2O), extracted (ethyl acetate), washed (H2O, brine), dried (MgSO1) and evaporated in vacuo. Purified by chromatography on silica gel using 50/50 ethyl acetate / hexane as eluent. The title compound was obtained as a white solid. ? NMR (250 MHz, CDCls) d 1.95 (HH, m), 2.15-2.19 (3H, m), 2.41-2.47 (2H, m), 3.61-3.65 (HH, m), 5.09 (2H, s), 7.49-7.59 (3H, m), 7.89 (HH, s), 8.39 (2H, m). Mass layer ES- (M + l) = 306.

EXAMPLE 186 A ^ -f4- (7-Cyclobutyl-3-phenyl-l, 2,4-triazoIor4,3-blpyrid-tzin-6-yloxy) but-2-inill-Ar, Ar-dimethylamine a) 6- (4-Chlorobut-2-infloxy) -7-cidobutyl-3-phene-1, 2,4-triazolo [4,3-blpiridazine Potassium carbonate (311 mg, 2.2 g) was heated to 50 ° C mmol) and 1,4-dichloro-2-butyne (275 mg, 2.2 mol) in DMF (3 ml), before adding, dropwise, the product of example 185, Step a (200 mg, 0.75 mmol) in DMF (2 ml). The reaction mixture was allowed to stir 2 hours, cooled and partitioned (ethyl acetate / water). The organic layer was washed (H2O, brine), dried (MgSO4) and evaporated in vacuo. Purified by chromatography on silica gel using 50/50 ethyl acetate / hexane as eluent. ? NMR (250 MHz, CDCls) d 1.93 (1H, m), 2.11-2.16 (3H, m), 2.42 (2H, m), 4.2 (2H, m), 5, 10 (2H, m), 7.50-7.59 (3H, m), 7.84 (1H, s), 8.47 (2H, m). b)? ^ f4- (7-Cidobutfl-3-fenü-l, 2,4-triazolo [4,3-bJpmdazin-6-ñoxi) -but-2-inüJ-? ^ - dimetflamina The previous product was heated ( 40 mg, 0.114 mmol) and dimethyamine (1 ml) in 1,4-dioxane (4 ml) in a sealed tube at 50 ° C for 60 minutes. Evaluating pore to ford. Purified by chromatography on silica gel using ethyl acetate / hexane 50/50 as eluent. The title compound was obtained as a white solid. vtí NMR (360 MHz, CDCls) d 1.93 (HH, m), 2.14 (3H, m), 2.25 (6H, s), 2.43 (2H, m), 3.30 (2H, s), 3.66 (ÍH, m), .09 (2H, s), 7.48-7.55 (3H, m), 7.82 (1H, s), 8.49 (2H, m).

EXAMPLE 187 2- [3- (3,7-Differential-l, 2,4-triazolof4,3-blpyridazin-6-yloxymethyl) -l, 2,4-triazole-l-ipetilamipa This compound was prepared using the procedure described in Example 176, using ethanolamine in place of iV.iV-dimethetanolamine. ? NMR (500 MHz, CDCl 3 + DMSO) d 3.12 (2H, t, J = 5.7 Hz), 4.23 (2H, t, J = 5.8 Hz), 5.62 (2H, s) , 7.54 (6H, m), 7.72 (2H, d, J = 7.9 Hz), 8.07 (HH, s), 8.29 (s, HH), 8.53 (2H, d, J = 7.4 Hz); MS (ES-) m / e 413 [MH-J.

EXAMPLE 188 3,7-PifePÍI-6-ri- (2- (pyrrolidip-1-yl) ethyl) -lg-1, 2,4-triazol-3-ylmethoxyl-l, 2,4-triazolof 4, 3-blpiridazine This compound was prepared using the procedure described in Example 176, using l- (2-hydroxyethyl) pyrroHdine instead of 7V, and V-dimethylethanolamine. ? NMR (400 MHz, CDCls) d 1.73 (6H, m), 2.47 (4H, s), 2.91 (2H, t, J = 6.4 Hz), 4.27 (2H, t, J = 6.4 Hz), 5.62 (2H, s), 7.50 (6H, m), 7.69 (2H, m), 8.04 (H, s), 8.17 (H, s), 8.55 (2H, m); MS (ES +) m / e 467 [MH-J.

EXAMPLE 189 6-fl- (l-MetiIpiperidip-4-ip-lg-l, 2,4-triazoi-3-ylmethoxyl-3,7-difyl-1,2,4-triazolof4,3-blpiridazine This compound was prepared using the procedure described in the example 176, using 4-hydroxy-l-methypiperidine instead of?,? - dimethetanolamine. ? NMR (400 MHz, CDCls) d 2.07 (6H, m), 2.33 (3H, s), 2.96 (2H, m), 4.13 (H, m), 5.61 (2H, s), 7.50 (6H, m), 7.70 (2H, m), 8.04 (HH, s), 8.09 (HH, s), 8.53 (2H, m); MS (ES-) m / e 467 [MH-J.

EXAMPLE 190 3,7-Phenylphenyl-6-fl- 2- (piperazip-1-yl) ethyl) -lg-1, 2,4-triazo-3-ylmethoxy-1, 2,4-triazolo [4,3- b] pyridazipa This compound was prepared using the procedure described in the example 176, using l- (2-hydroxyethyl) pi? Erazine in place of JV, iV-dimethetanolamine. ? NMR (400 MHz, CDCls) d 2.52 (4H, s), 2.77 (2H, t, J = 6.0 Hz), 2.92 (4H, s), 4.22 (2H, t, J = 5.9 Hz), 5.61 (2H, s), 7.52 (6H, m), 7.69 (2H, m), 8.05 (HH, s), 8.15 (HH, s), 8.54 (2H, m); MS (ES +) m / e 482 [MH-].

EXAMPLE 191 7- (l-Methylcyclopentyl) -6- 2-methyl-2-pyr-l, 2,4-triazol-3-ylmethoxy) -3- (2,4-difluorophenyl) -l, 2,4-triazole-4,3 -blpiridazipa It was prepared in a procedure analogous to that described in example 102a using 1-methylen-pentanoic acid, example 102b using 2,4-difluorobenzoic acid hydrazide and example 102c using 3-hydroxymethyl-2-methyl-2 // -1, 2. , 4-triazole, propordinating the title compound. ? NMR (250 MHz, CDCls) d 1.30 (3H, s), 1.68-1.94 (8H, m), 3.88 (3H, s), 5.50 (2H, s), 6, 99-7.14 (2H, m), 7.82-7.95 (3H, m), ms (ES-) m / e 426 [MH] -.

EXAMPLE 192 7- (Cyclobut-l-enip-6- (2-methyl-2g-l, 2,4-triazol-3-ylmethoxy) -3-fePIL-1, 2,4-triazolo [4,3-blpiridazine It was prepared in a procedure analogous to that described in example 102 by using 1-fluorine, oddobutanecarboxyHCO (ED Bergmann and S. Szinai, J. Chem. Soc, 1956, 1521) instead of acid cidopentanecarboxyHC in step (a), hydrazide of the benzoic acid in place of 2-thiophene carboxyHc acid hydrazide in step (b) and (2-metfl-2/7-l, 2,4-triazol-3-ü) methanol in place of 2-hydroxymethyrpyridine in step (c), propounding the title compound with a yield of 48%. ? NMR (360 MHz, CDCl 3) d 2.63 (2H, broad s), 2.89-2.87 (2H, m), 3.97 (3H, s), 5.66 (2H, s), 6 , 54 (ÍH, s), 7,58-7,51 (3H, s), 7,78 (ÍH, s), 7,95 (ÍH, s), 8,40-8,38 (2H, m ). MS (ES-) m / e 360 [MH] -.

EXAMPLE 193 7- (Furan-3-yl) -6-fl-methyl-lJy-l, 2,4-triazoI-3-ylmethoxy) -3-phetyl-l, 2,4-triazolo [4,3-blpiridazine This compound was prepared using procedures described in Example 139 using 3-furan boronic acid (J. Heterocycl Chem., 1975, 12, 195-196) instead of 2-thiophene boronic acid, m.p. 241 ° C. ? NMR (360MHz, CDCls) d 3.90 (3H, s), 5.62 (2H, s), 7.37 (ÍH, d, J = 1.8 Hz), 7.53-7.64 (3H , m), 7.85 (H, t, J = 1.8 Hz), 8.46 (3 H, m), 8.48 (H, s), 8.67 (H, s); MS (ES-) m / e 374 [MH-]. Analisys calculated C, 60.96; H, 4.06; N, 25.94. requires C, 61.12; H, 4.05; N, 26.26%.

EXAMPLE 194 JVt? ^ - Diethyl-A ^ r6-fl-methyl-lJ-r-l, 2,4-triazol-3-ylmethoxy) -3-fepyl-l, 2,4-triazolof4.3-blpiridaziP-7- illamine a)? r- (6-Chloro-3-fer-l, 2,4-triazolo [4,3-b]? iridazin-7-fl) - V, 7Vr-diethylphine This compound was prepared using the procedures described in Example 15, steps a, b, c and d using diethylamine in step c. b)? r,? f-Dieñ-r6- (l-metü-lg-l, 2,4-thiazol-3-flmetoxy) -3-phene-l, 2,4-triazolo [4,3 -b1-pyridazine-7-fljamine Sodium hydride (60% dispersion in oil, 34 mg, 0.36 mmol) was added to a solution of? f- (6-chloro-3-phen-1, 2,4-triazolo [ 4.3-b]? Iridazin-7-ü) -? R,? ^ - dietuamine (180 g, 0.33 mmol) and (l-metü-li7-l), 2,4-triazole-3-y) methanol (68 mg) in dry DMF (5 ml). The mixture was stirred at room temperature for 3 hours. The reaction mixture was diluted with water (50 ml) and extracted with dichloromethane (3 x 25 ml). The combined extracts were washed with brine, dried over magnesium sulfate, filtered and evaporated. The solid was recrystallized in ethyl acetate and collected by filtration to provide the title pyridazine (81 mg, 36%). ? NMR (500 MHz, DMSO-d6) d 1.08 (6H, t, J = 8.5 Hz), 3.31 (4H, q, J = 8.5 Hz), 3.87 (3H, s) , 5.50 (2H, s), 7.22 (HH, s), 7.47-7.59 (3H, m), 8.37 (2H, d, J = 8.5 Hz), 8, 51 (ÍH, s). MS (ES-) 379 [MH] -.

EXAMPLE 195 7- (1-Methylcyclopeptide) -6- (1-methyl-1-l, 2,4-triazol-3-ylmethoxy) -3- (2,4-difluorophene) -l, 2,4-triazole .3-blpiridazine It was prepared in a procedure analogous to that described in example 102a using of 1-metidodopentanoic acid, Example 102b using 2,4-difluorobenzoic acid hydrazide and Example 102c using 3-hydroxymethyl-1-n-et-1-l, 2,4-triazole, propounding the title compound. ? NMR (250 MHz, CDCls) d 1.33 (3H, s), 1.58-2.00 (8H, m), 3.93 (3H, s), 5.43 (2H, s), 6, 96-7.14 (2H, m), 7.92-8.05 (3H, m), ms (ES-) m / e 426 [MH] -.

EXAMPLE 196 7- (1, 1-Pimethylpropyl) -6- (l-methyI-lg-l, 2,4-triazol-3-ylmethoxy) -3-phenyl-l, 2,4-triazolo [4,3- blpiridazipa The compound was prepared using the procedures described in example 89, steps a), b) and c), using 2,2-dimethylbutyric acid in place of carboxylic acid cidohexane in step c). Data for the title compound:? NMR (360 MHz, CDCl 3) d 0.70 (3H, t, = 7.5 Hz), 1.41 (6H, s), 1.89 (2H, q, J = 7.5 Hz), 3, 94 (3H, s), 5.58 (2H, s), 7.46-7.56 (3H, m), 7.90 (H, s), 8.06 (H, s), 8.51 (2H, d, J = 8.0 Hz); MS (ES-) m / e 378 [MH] -. Analisys calculated C, 63.48; H, 6.19; N, 25.55. C20H23N7O1 requires C, 63.34; H, 6.17; N, 25.85%.

EXAMPLE 197 6- (2-Methyl-2g-l, 2,4-triazol-3-ylmethoxy) -3- (4-fluorophenyl) -7- (thiophen-3-yl) -l, 2,4-triazole 4, 3- blpiridazine This compound was prepared using the procedures described in the example 16, steps a), b) and c) except that 3-thiophene boronic acid was used in place of 4-pyridin boronic acid, di-HTH salt in step a), 1.1 equivalents of 4-fluorobenzohydrazide and triethyl amine hydrochloride in step b) instead of 1.1 equivalents of benzohydrazide, addo / toluenesulfonic acid and triethyl amine and (2-methan-2-fl, 2,4-triazol-3-yl) methanol (example 66) was used in step c) instead of 2-? iriducarbinol. Data for the title compound: p.f. 268-269 ° C (MeOH). ? NMR (360 MHz, DMSO) d 3.92 (3H, s), 5.79 (2H, s), 7.46 (2H, t, J = 9 Hz), 7.70-7.74 (2H, m), 8.01 (HH, s), 8.19-8.21 (HH, m), 8.45-8.49 (2H, m), 8, 68 (ÍH, s). MS (ES-) 408 [MH] -. Analysis calculated C, 55.90; H, 3.44; N, 24.02. C19H14N7FOS requires C, 56.01; H, 3.46; N, 24.07%.

EXAMPLE 198 6- methyl-lg-l, 2,4-triazol-3-ylmethoxy) -3- (4-fluorophenyl) -7- (thiophen-3-yl) -l, 2,4-triazoIof4.3- blpiridazine This compound was prepared using the procedures described in example 16, steps a), b) and c) except that 3-thiophene boronic acid was used in place of 4-pyridin boronic acid, di-HTH salt in step a), 1.1 equivalents of 4-fluorobenzohydrazide and triethnamine hydrochloride were used in step b) instead of 1.1 equivalents of benzohydrazide, iodine / > toluenesulfonic acid and triethyl amine and (l-metul-l-l-r-l, 2,4-triazol-3-yl) methanol (example 65) was used in step c) in place of 2-pyridylcarbinol. Data for the title compound: p.f. 254-255 ° C (MeOH). ? NMR (360 MHz, DMSO) d 3.89 (3H, s), 5.61 (2H, s), 7.46 (2H, t, J = 9 Hz), 7.71 (ΔI, dd, J = 5, 3 Hz), 7.80 (OH, dd, J = 5, l Hz), 8.28-8.29 (lH, m), 8.51-8.56 (3H, m), 8, 67 (ÍH, s). MS (ES-) 408 [MH] -. Calculated Analysis C, 55.88; H, 3.40; N, 23.98. O9H14N7FOS requires C, 56.01; H, 3.46; N, 24.07%.

EXAMPLE 199 6- (2-Methyl-2g-l, 2,4-triazol-3-ylmethoxy) -3- (2-fluoropheni0-7- (thiofep-3-yl) -l, 2,4-triazolof4,3 - blpiridazine • 0.6 (Hydrate) This compound was prepared using the procedures described in example 16, steps a), b) and c) except that 3-thiophene boronic acid was used in place of 4-pyridin boronic acid, di-HTH salt in step a), 1.1 equivalents of 2-fluorobenzohydrazide were used and triethyl amine hydrochloride in step b) instead of 1.1 equivalents of benzohydrazide, áddo / 7-toluenesulfonic acid and triethynamine and (2-metñ-2/7-l, 2,4-thiazol-3-yl) methanol was used (example 66) in step c) in place of 2-pyriducarbinol. Data for the title compound: p.f. 175-176 ° C (MeOH). ? NMR (360 MHz, DMSO) d 3.81 (3H, s), 5.66 (2H, s), 7.48-7.59 (2H, m), 7.70-7.80 (3H, m) ), 7.96-8.02 (2H, m), 8.24 (1H, dd, J = 4, 3 Hz), 8.75 (1H, s). MS (ES-) 408 [MH] -. Calculated Analysis C, 54.58; H, 3.94. C19H14N7FOS. 0.6 H20 requires C, 54.56; H, 3.66%.

EXAMPLE 200 3- (2-Fluorophenyl) -7- (1-methylcyanobutyl) -6-r 2 -methyl-2g-1, 2,4-triazol-3-ylmethoxy) -l, 2,4-triazolof 4,3-blpiridazine The compound was prepared using the procedures described in example 102, steps a), b) and c) using 1-methyclobutane carboxylic acid (U.S. patent 4,220,795) instead of carboxyco acid cidopentane acid in step a), using 2-fluorobenzohydrazide in place of 2-thiophene carboxyHc acid hydrazide in step b) and using (2-metfl-2Zf-1, 2,4-triazol-3-y) methanol (prepared using the conditions described in EP -A-421210) instead of 2-hydroxymethylpyridine in step c). Data for the title compound:? NMR (360 MHz, CDCls) d 1.51 (3H, s), 1.80-1.90 (HH, m), 2.04-2.24 (3H, m), 2.35-2.46 (2H, m), 3.82 (3H, s), 5.47 (2H, s), 7.27 (HH, wide t, J = 7 Hz), 7.34 (HH, broad t, J = 7ß Hz), 7,53-7,60 (ÍH, m), 7,73 (ÍH, s), 7,85 (ÍH, wide t, J = 7,5 Hz), 7,88 (ÍH, s ); MS (ES-) m / e 394 [MH] -. Analisys calculated C, 61.16; H, 5.14; N, 24.90. C20H20N7OF requires C, 61.06; H, 5.12; N, 24.92%.

EXAMPLE 201 3- (2-Fluorophenyl) -7- (l-methylcyclobutyn-6- (l-methyl-lg-l, 2,4-triazoi-3-ylmethoxy) -l, 2,4-triazoIor4,3-blpiridazine The compound was prepared using the procedures described in example 102, steps a), b) and c) using 1-methydodobutane carboxylic acid (U.S. patent 4,220,795) instead of carboxylic acid ddopentane in step a), using 2-fluorobenzohydrazide in place of the hydrazide of the 2-thiophene carboxyHC acid in step b) and using (1-methyl-1/1, 2,4-triazole-3-yl) methanol (prepared using the conditions described in the document EP-A-421210) in place of 2-hydroxymethyridine in step c). Data for the title compound: H NMR (360 MHz, CDCls) d 1.54 (3H, s), 1.78-1.88 (1H, m), 2.04-2.22 (3H, m) , 2.37-2.45 (2H, m), 3.92 (3H, s), 5.40 (2H, s), 7.23-7.34 (2H, m), 7.49-7 , 55 (H, m), 7.69 (H, s), 7.95 (H, broad t, J = 7 Hz), 8.02 (H, s); MS (ES-) m / e 394 [MH] -. Analysis calculated C, 61.10; H, 4.96; N, 24.79. C20H20N7OF requires C, 61.06; H, 5.12; N, 24.92%.

EXAMPLE 202 6- (1-Methyl-1-pyr-1, 2,4-triazo-3-ylmethoxy) -3- (2-fluorophenyl) -7- (thiophen-3-yl) -l, 2,4-triazole-4, 3- blpiridazine This compound was prepared using the procedures described in the example 16, steps a), b) and c) except that 3-thiophene boronic acid was used in place of 4-pyridine boronic acid, di-HTH salt in step a), 1.1 equivalents of 2-fluorobenzohydrazide and triethyl amine hydrochloride in step b) in place of 1.1 equivalents of benzohydrazide, p-toluenesulfonic acid and triethimamine, and (l-meth-L-1, 2,4-triazole-3-fl) methanol was used (example 65) in step c) in place of 2-pyriducarbinol. Data for the title compound: p.f. 216-218 ° C (MeOH). ? NMR (360 MHz, DMSO) d 3.93 (3H, s), 5.50 (2H, s), 7.48-7.59 (2H, m), 7.69- 7.78 (2H, m), 7.85 (HH, dd, J = 7, 2 Hz), 8.08-8.14 (HH, m), 8.34 (HH, dd, J = 4, 2 Hz), 8.58 (H, s), 8.77 (H, s). MS (ES-) 408 [MH] -. Calculated Analysis C, 55.82; H, 3.57; N, 24.30. C? 9Hi4N7FOS requires C, 56.01; H, 3.46; N, 24.07%.

EXAMPLE 203 8-Methyl-7-fl-methylcyclobutyl) -6- (l-methyl-lg-l, 2,4-triazol-3-itmethoxy) -3-fePl-1,2,4-triazolo [4,3-blpiridazine The compound was prepared using the procedures described in example 102, steps a), b) and c) using 1-methylbutane carboxylic acid (U.S. patent 4,220,795) and using 3,6-dimer-4-methypyridazine instead of cyclopentane carboxycocide and 3,6-dichloropyridazine, respec- tively, in step a), and using benzoic acid hydrazide in place of 2-thiophene carboxylic acid hydrazide in step b), and using (1-meth- '-rl, 2,4-triazol-3-ü) methanol (prepared using the conditions described in EP-A-421210) in place of 2-hydroxymethyrpyridine in step c). Data for the title compound:? NMR (360 MHz, CDCls) d 1.57 (3H, s), 1.74-1.84 (HH, m), 2.02-2.14 (HH, m), 2.20-2.26 (2H, m), 2.50-2.58 (2H, m), 2.62 (3H, s), 3.93 (3H, s), 5.48 (2H, s), 7.44- 7.54 (3H, m), 8.04 (HH, s), 8.49 (2H, d, J = 8 Hz); MS (ES-) m / e 390 [MHJ-. Analysis calculated C, 64.74; H, 5.92; N, 24.88. C 21 H 23 N 7 O requires C, 64.76; H, 5.95; N, 25.18%.

EXAMPLE 204 8-MetiI-7- (1-methyclobutyl) -6- (2-methyl-2 g-1, 2,4-triazol-3-ylmethoxy) -3-fep-1, 2,4-triazole-4,3- bl pyridazine The compound was prepared using the procedures described in the example 102, steps a), b) and c) using 1-methyclobutane carboxylic acid (United States patent) U.S. 4,220,795) and using 3,6-dichloro-4-methypyridazine instead of dclopentane carboxyHc acid and 3,6-dichloropyridazine, respec- tively, in step a), and using benzoic acid hydrazide in place of the acid hydrazide. -thiophene carboxylic acid in step b), and using (2-metfl-2-Yl, 2,4-triazol-3-y) methanol (prepared using the conditions described in EP-A-421210) instead of 2 -hydroxymethyripine in step c). Data for the title compound:? NMR (360 MHz, CDCls) d 1.54 (3H, s), 1.76-1.84 (ÍH, m), 2.04-2.16 (3H, m), 2.46-2.53 (2H, m), 2.64 (3H, s), 3.94 (3H, s), 5.53 (2H, s), 7.46-7.56 (3H, m), 7.93 ( ÍH, s), 8.34 (2H, d, J = 8 Hz); MS (ES-) m / e 390 [MH] -. Analisys calculated C, 64.83; H, 5.82; N, 25.04. C 21 H 23 N 7 O requires C, 64.76; H, 5.95; N, 25.18%.

EXAMPLE 205 6- i-Methyl-lJtr-l, 2,4-triazol-3-ylmethoxy) -3-phenyl-7- (pyrrolidin-1-yl) -l, 2,4-triazolo [4,3-b-pyridazine ? NMR (250MHz, CDCls) d 1.95-2.00 (4H, m), 3.53-3.58 (4H, m), 3.95 (3H, s), 5.55 (2H, s) , 6.69 (H, s), 7.41-7.55 (3H, m), 8.07 (H, s), 8.43-8.45 (2H, m), ms (ES +) ( M + l) = 377.

EXAMPLE 206 7-Cyclobutyl-8-methyl-6- (2-metii-2g-l, 2,4-triazol-3-ylmethoxy) -3-phenyl-1, 2,4-triazolo [4,3-blpyridazine Prepared in a procedure analogous to that described in example 102a using 1-methyclobutane carboxy carboxylate, example 102b using benzoic acid hydrazide and example 102c using 3-hydroxymethylene-2-methyl-2,4-triazole, providing the title compound. ? NMR (360 MHz, CDCls) d 2.06-2.09 (2H, m), 2.26 (3H, s), 2.42-2.50 (2H, m), 3.04-3.17 (2H, m), 3.97 (3H, s), 4.06 (ÍH, t, J = 10 Hz), 5.57 (2H, s), 7.48-7.56 (3H, m) , 7.92 (ΔI, s), 8.36 (2H, d, J = 7.7 Hz), ms (ES-) m / e 376 [MH] -.

EXAMPLE 207 7-Cyclobutyl-8-methyl-6- (l-methi [-lg-l, 2,4-triazol-3-ylmethoxy) -3-phenyl-l, 2,4-triazoloyl-4,3-blpiridazine Prepared in a procedure analogous to that described in Example 102a using 1-methyclobutane carboxyHC acid, Example 102b using benzoic acid hydrazide and Example 102c using 3-hydroxymethyl-1-methyl-7 -7, 2,4-triazole, propordonand the title compound. ? NMR (360 MHz, CDCls) d 2.06-2.18 (2H, m), 2.24 (3H, s), 2.40-2.50 (2H, m), 3.02-3.16 (2H, m), 3.84 (3H, s), 3.88-4.10 (HH, m), 5.50 (2H, s), 7.42-7.56 (3H, m), 8.04 (HH, s), 8.48-8.52 (2H, m), ms (ES-) m / e 376 [MH] -.

EXAMPLE 208 7- (l-Methylcyclopentip-6-r 2 -methyl-2-flu-1, 2,4-triazo-3-ylmethoxy) -3- (2-fluorophenyl) -l, 2,4-triazol-4,3-bl-pyridazine Prepared in an analogous procedure to that described in example 102a using 1-methylenecyclopentanoic acid, example 102b using 2-fluorobenzoic acid hydrazide and example 102c using 3-hydroxymethyl-2-methan-2-l, 2,4-triazole, providing the title compound,? NMR (360 MHz, CDCls) d 1.31 (3H, s), 1.72-1.90 (8H, m), 3.82 (3H, s), 5.50 (2H, s), 7, 25-7.37 (2H, m), 7.53-7.59 (HH, m), 7.83-7.87 (HH, m), 7.90 (HH, s), 7.94 ( ÍH, m), ms (ES-) m / e 409 [MH] -.

EXAMPLE 209 7- (l-Methylcyclopentyl) -6- (l-methyl-lg-l, 2,4-triazol-3-ylmethoxy) -3-r2-fluorophenyl) -l, 2,4-triazole-4,3-bl pyridazine Prepared in a procedure analogous to that described in Example 102a using 1-Methyldopentanoic acid, Example 102b using 2-fluorobenzoic acid hydrazide and Example 102c using 3-hydroxymethyl-1-methyl-1-l-1, 2,4-triazole, propordinating the title compound. ? NMR (360 MHz, CDCU) d 1.33 (3H, s), 1.70-1.93 (8H, m), 3.92 (3H, s), 5.43 (2H, s), 7, 23-7.34 (2H, m), 7.49-7.55 (HH, m), 7.90 (HH, s), 7.94-7.98 (HH, m), 8.04 ( ÍH, m), ms (ES-) m / e 409 [MH] -.

EXAMPLE 210 7-Cyclobutyl-6-f4- (2,6-dimethylmorpholin-4-yl) but-2-ynyloxyl-3-phetyl-l, 2,4-triazolo [4,3-blpiridazine ? NMR (250MHz, CDCls) d 1,11 (3H, s), 1,13 (3H, s), 1,21 (ÍH, m), 1,92 (3H, m), 2,13-2,20 (3H, m), 2.39-2.45 (2H, m), 2.68 (2H, m), 3.33 (2H, m), 3.59-3.69 (3H, m), 5.09 (2H, m), 7.46-7.58 (3H, m), 7.82 (IH, d, J = 1.6 Hz), 8.50 (2H, m), ms (ES -) (M + l) = 432.

Claims

NOVELTY OF THE INVENTION CLAIMS:

1. - A compound of formula I, or a salt or prodrug thereof: (i) wherein Y represents hydrogen or C alqu-6 alkyl; and Z represents C alqu - alkanoy, C3-7 cycloalkyl, C4-7 ddoalkonium, aryl, (C3-7 heterocycle) alkyl, heteroaryl or di (C -6 alkyl) amino, any of said groups being optionally substituted; or Y and Z are taken together with the two intermediate carbon atoms to form a selected ring of C5-9alidoalkenyl, C6-10 bicidoalkenyl, tetrahydropyridinone, pyridinium and phenol, any of said rings optionally being benzocondensate and / or substituted; R1 represents C3-7 cycloalkyl, phenol, furyl, thienyl or pyridinium, any of said groups optionally substituted; and R2 represents cyanoalkon (C? -6), hydroxyalkyl (C? _6), (C3-7 cycloalkyl) (Ci_? alky), proparg? n, (C3-7 heterodod) alcarbonbon (C1_6 alky), ar? C1-6) or heteroaryl (Ci-ß alkyl), any of said groups being optionally substituted; a condition that, when Y and Z are taken together with the two intermediate carbon atoms to form an opponally substituted phenyl ring, then R2 is not hydroxy (C? -6 alk).

2. A compound according to claim 1, represented by the formula HA, and the salts and prodrugs thereof: (HA) wherein R1 is as defined in claim 1; n is 1, 2, 3 or 4; and R 12 represents hydroxy; or C3-7alkidoalkyl, (C3-7 heterocycle) alkanocarbon, aryl or heteroaryl, any of said groups optionally substituted.

3. A compound according to claim 1, represented by formula IIB, and the salts and.-Prodrugs thereof: (IIB) wherein Y1 represents hydrogen or methno; Z1 represents C1-6 alkane, C3-7alkanoalkyl, C4-7 cycloalkenyl, aryl, (heterogenous Cs-7) alken, heteroaryl or di (C? .6 alkylamino), any of said groups being optionally substituted; R1 is as defined in claim 1; m is 1 or 2; and R22 represents aryl or heteroaryl, any of said groups optionally substituted.

4. A compound according to claim 3, represented by the formula IIC, and its pharmaceutically acceptable salts: (IIC) in which.-R1 is as defined in claim 1; Q represents the remainder of a ring of cyclopropyl, cyclobutyl, cidopentone or cidohexene; R5 represents hydrogen or methylo; and R6 represents hydrogen or meth.

5. A compound selected from: 3-fenfl-6- (2-pyridine) metfloxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4 -a] phthalazine; 3,7-difenu-6- (2-pyridine) methoxy-l, 2,4-triazolo [4,3-b] pyridazine; 3-phenyl-6- (2-pyridu) methyloxy-7,8,9,10-tetrahydro-l, 2,4-triazolo [3,4-ajftalazine; 7,8-dirnetü-3-fenñ-6- (2-? Iridü) rnetüoxi-l, 2,4-triazolo [4,3-b] pyridazine; 7-methyl-3-phenyl-6- (2-pyridu) methyloxy-l, 2,4-triazolo [4,3-bJ-iridazine; 7-ethe-3-phenyl-6- (2-pyridu) methoxy-l, 2,4-thi-iazolo [4,3-b]? Iridazine; 7,8-benzo-3-phenyl-6- (2-pyridu) methoxy-7,8,9,10-tetrahydro-l, 2,4-triazolo [3,4-a] phthalazine; 8-metñ-3,7-difenñ-6- (2-pyridu) methyloxy-l, 2,4-triazolo [4,3-b] pyridazine; 3-Phene-6- (2-pyridu) methoxy-7,8,9,10-tetrahydro- (7,10-methane) -l, 2,4-triazolo [3,4-a] phthalazine; 3-fer-ü-5- (pyridin-2-ümethoxy) -l, 2,3a, 4,7-pentaazacyclopenta [o] naphthalene; 3-phene-5- (pyridin-2-ümethoxy) -l, 2,3a, 4,8-pentaazacyclohexa [a] naphthalene; 8-methyl-3-phene-6- (2-pyridine) methyloxy-7,8,9,10-tetrahydro-l, 2,4-triazolo [3,4-a] phthalazine; 3-Phen-6- (2-pyridine) methyloxy- (7,8-? -ethane) -l, 2,4-triazolo [4,3-b] pyridazine; 8,8-dimethy-3-phene-6- (2-pyridine) methyloxy-7,8,9,10-tetrahydro-l, 2,4-triazolo [3,4-a] phthalazine; 3-phene-7- (pi? Eridin-1-y) -6 - (? Iridin-2-ymetoxy) -l, 2,4-triazolo [4,3-bjpyridazine; 3-phene-7- (pyridin-4-y) -6- (pyridin-2-urea) -l, 2,4-triazolo [4,3-b] pyridazine; 3-phenyl-5- (pyridin-2-υmethoxy) -6,7,8,9-tetrahydro-l, 2,3a, 4,8-α-entazaza-cidopenta [a] naphthalene; 3- phene-5- (α-din-2-yltrnetoxy) -6,7,8,9-tetiahydro-l, 2,3a, 4,7-pentaaza-cido-enta [2] naphthalene; 7-? Netü-3-fenñr5- (pMdin-2-iln? Ethoxy) -6,7,8,9-tetiahydro-l, 2,3a, 4,7-pentaazacyclopenta [a] naphthalene; 3-phenyl-6- (pmdin-2-ümethoxy) -7- (thiophen-2-ü) -l, 2,4-triazolo [4,3-b-pyridazine; 3-phenyl-6- (pyridin-2-ümeto-i) -7- (thiophen-3-y) -l, 2,4-triazolo [4,3-b] pyridazine; 3-phenyl-6- (2-pyridine) methoxy-7,8,9,10-tetrahydro- (7,10-propane) -l, 2,4-triazolo [3,4-a] phthalazine; 3- (4-methyl) phenyl-6- (2-pyridine) methoxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-ajftalazine; 3- (3-methoxy) phen-6- (2-p? Dü) methyloxy-7,8,9,10-teteahydro- (7,10-ethane) -l, 2,4-triazolo [3,4- a] phthalazine; 3- (2-fluoro) phenyl-6- (2-pyridu) methoxy-7,8,9,10-tetramdro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 3- (3-pyridine) -6- (2-pmdü) methyloxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 3-Cidopropyl-6- (2-pyridu) methyloxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 6 - [(6-metü) -2-pmdü] metuoxy-3-phene-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a ] phthalazine; 6 - [(3-metü) -2-pyridine] methyloxy-3-ferul-7,8,9,10-tetra] -? Idro- (7,10-ethane) -l, 2,4-triazolo [3 , 4-a] phthalazine; 6 - [(4-metü) -2-pyridine] methoxy-3-phene-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-ajftalazine; 6 - [(5-metü) -2-pyridine] methoxy-3-phene-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a ] phthalazine; 3-Phene-6- (3-pyridu) methyloxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-tthiazolo [3,4-a] phthalazine; 3-phenyl-6- (4-pyridine) methyloxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 3-Phen-6- [2- (1-methane) imidazole] methyloxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 6- (3-d-ofenu) methyloxy-3-ferul-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 6- [l- (3,5-dimethyl) pyrazol] methyloxy-3-phen-7,8,9,10-te ± Ehydro- (7,10-ethane) -l, 2,4-triazolo [3, 4-a] phthalazine; 6- [4- (2-metñ) thiazoHl] metuoxy-3-phene-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 3-phenyl-6- (2-quinoxalinu) nxethoxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 3-phenyl-6- (3-? Iridazin) methoxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 6- (L-benzimidazole-2-ü) methoxy-3-fenfl-7,8 ^, 10-tetraMdro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 3-Phen-6- (isoquinoline-1-y) methoxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 6- (1-ethylimidazol-2-y) methnoxy-3-phene-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-aJphtalazine; 3-fenñ-6- (l- ? 28? Irazolu) metfloxy-7,8,9,10-tetramdro- (7,10-ethane) -l, 2,4-tthiazolo [3,4-a] phthalazine; S-phenyl-or-^ -pyrroHdincarbonyl) rnethoxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 6- [4- (3-metñ) p? DüJmetnoxy-3-phene-7,8,9,10-teteahidro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 3-phenyl-6 -); 2-quinoHnñ) methoxy-7,8,9,10-tetiahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 6- (2-imidazole) methyloxy-3-phene-7,8,9,10-tetral-idro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 3-phene-6- (2-thiazole) p? Ethoxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 6- [2- (5-metñ) thiazo-jmethnoxy-3-phene-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 6- [2- (4-metü) thiazo jmetüoxi-3-ferul-7,8,9,10-tetrahicko- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phtala2ma; 6- [2- (3,5-dimetü) p? Dñ] methyloxy-3-phenyl-7,8,9,10-tettahydro- (7,10-ethane) -l, 2,4-triazolo [3, 4-ajftalazine; 3-fe ????????????? 6- (2-p azmñ) metuoxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-ajftalazine; 6- [2- (4,6-dimethyl) pyridu] methyloxy-3-phene-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4- aJftalazine; 3-phenyl-6- (4-thiazole) methoxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-aJ-phthalazine; 6- [2- (5,6-dimethyl) pyridine] methoxy-3-phene-7,8,9,10-tetrahydro- (7,10-ethanoj-1'-triazole) -S-phthalazine; methynidazole-2-ü) methyloxy-3-phen-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 3-phenol 6- (4-pyrimidinu) methoxy-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-ajftalazine; 6- [4- (2-eti ) thiazole] methyloxy-3-phene-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 6- (6-chloropyridazine- 3-ü) methoxy-3-phene-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 6- (2-imidazole) ) methyloxy-3- (4-methylen) -7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; hydr0ximetüfenñ) methoxy-3-phene-7,8,9, lO-tetrahydro- (7, lO-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 6- (4-? -roxibutfl ) oxy-3-phen-7,8,9,10-tetraMdro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 6- (4-hydroxymethylenehexñ) methoxy- 3-phene-7,8,9, 1 C) -tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-ajftalazine; 6- (3-hydroxymethylphen) methoxy-3-phen-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 6- (l-metü-l, 2,4-triazol-3-ü) metuoxy-3-phene-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 6- (2-metñ-l, 2,4-triazol-3-y) methyloxy-3-phene-7,8,9,10-tetrahydro- (7,10-ethano) -l, 2/4-triazolo [3,4-a] phthalazine; 3-fenñ-6- (3-ddopropñmetüoxi-2- pMdn)? netuoxo-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a] phthalazine; 3-phenyl-6- (3-ethoxy-2-pmdü) n? Etuboxi-7,8,9,10-tetrahydro- (7,10-ethane) -l, 2,4-triazolo [3,4-a ] phthalazine; and the salts and prodrugs thereof.

6. A compound selected from: 6- (6-metñpyridin-2-ü) methoxy-3-phene-1, 2,4-triazolp [3,4-aJ-phthalazine; and the salts and prodrugs thereof.

7. A compound selected from: 6- (l-met-177-l, 2,4-triazol-3-y-methoxy) -3,7-diphen-l, 2-triazolo [4,3-b-pyridazine; 6- (2-methan-2 / r-1, 2,4-triazol-3-methoxy) -3,7-diphenol, 2,4-triazolo [4,3-b] pyridazine; 3,7-diphen-6- (2/1-l, 2,4-triazol-3-methoxy) -l, 2,4-triazolo [4,3-bjpyridazine; 6- (2-metñ-2 / -tetrazol-5-urea) -3,7-düenü-l, 2,4-triazolo [4,3-b] -pyridazine; 3,7-dü: enñ-6- (2-pro? -2-l, 2,4-triazol-3-y-methoxy) -l, 2,4-triazolo [4,3-b] pyridazine; 3,7-DTPENN-6- (1-propyl-1-Y-1, 4, 4-triazol-3-i-methoxy) -1,4-triazolo [4,3-bJp dazine; © - (l-metñ-l / f-imidazoM-ñmethoxy) -3,7-difenü-l, 2,4-triazolo [4,3-b]? Irida2rin; 6- (3-methan-3'-imidazol-4-ylmethoxy) -3,7-diphen-l, 2,4-triazolo [4,3-b-pyridazine; 6- (4-metü-4 /? - l, 2,4-triazol-3-ümethoxy) -3,7-diphenol, 2,4-triazolo [4,3-b] pyridazine; 6- (5-methyl-2-flu-1, 2,4-triazol-3-methoxy) -3,7-diphenol, 2,4-triazolo [4,3-bjpyridazine; 6- (3-methy-3? -l, 2,3-triazol-4-methoxy) -3,7-diphen-l, 2,4-triazolo [4,3-b] pyridazine; 3- (4-methoxiferm) -6- (l-metñ-li7 ^ -l, 2,4-triazol-3-ümethoxy) -7-fenü-l, 2,4-triazolo [4,3-b]? iridazine; 6- (3-metñ? Iridin-2-ihetoxy) -3-phene-7- (piperidin-1-y) -l, 2,4-triazolo [4,3-b] pyridazine; 7- (? Norfolin-4-ü) -3-phene-6- (pyridin-2-ümethoxy) -l, 2,4-triazolo [4,3-b] pyridazine; 3-Phen-7- (pyridin-3-y) -6- (pyridin-2-ylmethoxy) -l, 2,4-triazolo [4,3-b] pyridazine; 8-metü-6- (2-metü-2ff-l, 2,4-triazol-3-ymetoxy) -3,7-diphenol, 2,4-triazolo [4,3-b] pyridazine; 6- (l-metñ-lií-l, 2,4-triazol-3-ñmethoxy) -7- (morfoHn-4-ñ) -3-fenü-l, 2,4-triazolo [4,3-b] pyridazine; 6- (2-metü-2ff-l, 2,4-triazol-3-ümethoxy) -7- (morfoHn-4-y) -3-phen-1, 2,4-triazolo [4,3-b-pyridazine; 7-ddohexyl-6- (2-methan-2Zf-1, 2,4-triazol-3-ymetoxy) 3-yenyl-l, 2,4-triazolo [4,3-b] pyridazine; 7-cidohexii-6- (l-metü-líT-l, 2,4-triazol-3-ymetoxy) -3-phene-l, 2,4-triazolo [4,3-b] pyridazine; 7-Cidopentyl-6- (2-methyl-2-yl, 2,4-triazol-3-ylmethoxy) -3-phenol-l, 2,4-triazolo [4,3-b-pyridazine; 8-metü-6- (l-metü-líf-l, 2,4-triazol-3-ñmethoxy) -3,7-difenü-l, 2,4-triazolo [4,3-b] pyridazine; 7-ddobutñ-6- (l-metñ-lfí-l, 2,4-triazol-3-ümetoxi) -3- fenü-l, 2,4-triazolo [4,3-b-pyridazine; 7-ert-butyl-6- (2-netu-2? -l, 2,4-triazol-3-ylmethoxy) -3-phen-1, 2,4-triazolo [4,3-b] pyridazine; 7-Cidobutyne-6- (2-methy-2-pyr-l, 2,4-triazol-3-methoxy) -3-phenyl-1, 2,4-triazolo [4,3-b]? Iridazine; 7-ethyl-6- (2-methan-2ff-l, 2,4-triazol-3-ymetoxy) -3-phenyl-2,4-triazolo [4,3-b] pyridazine; 7-te c-butñ-6- (l-? Netü-lií-l, 2,4-triazol-3-ylmethoxy) -3-fenñ-l, 2,4-triazolo [4,3-bjpiridazina; 7-ethan-6- (l-methan-l-l, 2,4-triazol-3-yl-hetoxy) -3-phen-l, 2,4-triazolo [4,3-b] pyridazine; 7-methy-6- (2-methan-2F-1, 2,4-triazol-3-γ-methoxy) -3-phenyl-2,4-triazolo [4,3-b] pyridazine; 7- (l-? Net3lddobutü) -6- (2-n? Etü-2 -rl, 2,4-triazol-3-yl? Netoxy) -3-phen-l, 2,4-triazolo [4,3 -b] pyridazine; 7-rnetü-6- (l-rnetü-li? -l, 2,4-triazol-3-ylmethoxy) -3-phene-l, 2,4-thiazolo [4,3-b] pyridazine; 7-cidobutyl-3-phenyl-6- (2-r-l, 2,4-triazol-3-υmethoxy) -l, 2,4-triazolo [4,3-b] pyridazine; 7-Cido-enti-6- (pyridin-2-ümethoxy) -3- (thiophen-2-y) -l, 2,4-triazolo [4,3-b-pyridazine; 7-dclopentin-3- (2,4-difluorophenyl) -6- (1-methyl-1-l, 2,4-triazol-3-methoxy) -l, 2,4-triazolo [4,3-b ] pyridazine; 7-ddopentñ-6- (l-metñ-lflr-l, 2,4-triazol-3-ylmethoxy) -3- (thiophen-2-y) -l, 2,4-triazolo [4,3-b] ? iridazine; 7-ddopentü-6- (2-metñ-2ff-l, 2,4-triazol-3-ümethoxy) -3- (thiophen-2-y) -l, 2,4-triazolo [4,3-b] pyridazine; 7-dclopentyl-6- (2-rnetñ-2 ^ -l ^, 4-triazol-3-ü? Netoxy) -3- (pMdin-4-ü) -l, 2,4-triazolo [4,3- b] pyridazine; 7-Cidopentyl-3- (2-fluorophenyl) -6- (l-metñ-l / -l, 2,4-triazol-3-ümethoxy) -l, 2,4-triazolo [4,3-b] pyridazine; 7-ddopentyl-3r (2-fluorophenone) -6- (2-methy-2i / -l, 2,4-triazol-3-ümethoxy) -l, 2,4-triazolo [4,3-bjpyridazine; 7-Cyclo? Enti-3- (2-fluorofenu) -6- (pyridin-2-ymetoxy) -l, 2,4-triazolo [4,3-b] pyridazine; 7-cyclopentyl-3- (2,4-dluorophenone) -6- (2-methan-2'-l, 2,4-triazol-3-ylmethoxy) -l, 2,4-triazolo [4,3- b] pyridazine; 7-dclo? Entu-3-phenyl-6- (pyridin-2-ümethoxy) -l, 2,4-triazolo [4,3-b]? Iridazine; 7-cidopentin-8-methu-6- (2-methan-2-Y-l, 2,4-triazol-3-ymetoxy) -3-phen-1, 2,4-triazolo [4,3-bJ-iridazine; 7-dclopentyl-3-phenyl-6- (2'-l, 2,4-triazol-3-methoxy) -l, 2,4-triazolo [4,3-bjpyridazine; 3- (4-methylHer) -7-phenyl-6- (pMdin-2-ymetoxy) -l, 2,4-triazolo [4,3-b] pyridazine; 3- (4-metüfenü) -6- (3-metüpmdin-2-ñrnetoxi) -7-fenü-l, 2,4-triazolo [4,3-bJ? Iridazine; 6- (l-etñ-líT-irnidazol-2-ü? Netoxi) -3- (4-? Netüfenü) -7-fenü-l, 2,4-triazolo [4,3-b] pyridazine; 3-phenyl-6- (pyridin-2-ümethoxy) -7- (thiomorpholin-4-ü) -l, 2,4-triazolo [4,3-b] pyridazine; 6- [2- (4-methanediazol-5-ü) ethoxy] -3,7-diphen-l, 2,4-triazolo [4,3-b]? Iridazine; (±) -7- (2-metñpirroHdin-l-ü) -3-fenñ-6- (piridin-2- γ-methoxy) -l, 2,4-triazolo [4,3-b] pyridazine; 6- (l-methane --- / Y-l, 2,4-triazol-3-ylmethoxy) -3-phene-7- (pyridin-4-yl) rl, 2,4-triazolo [4,3-b-pyridazine; 7-ddo? Entyl-6- (l-metii-liY-l, 2,4-triazol-3-ymetoxy) -3-ferul-l, 2,4-triazolo [4,3-b] pyridazine; 7-iso? Ro? Ü-6- (l-metü-li7-l, 2,4-triazol-3-ylmethyl) -3-phen-l, 2,4-triazolo [4,3-b ] pyridazine; 3-cido? Ropii-6- (l-metñ-l // -l, 2,4-triazol-3-ümethoxy) -7-phenü-l, 2,4-triazolo [4,3-b] pyridazine; 3- (2-fluorophenyl) -6- (2-methyl-2-flu-1, 2,4-triazol-3-methoxy) -7-phen-1, 2,4-triazolo [4,3-b] pyridazine; 3- (2-fluorophenone) -6- (1-methan-1-yl, 2,4-triazol-3-ylmethoxy) -7-phenyl-1, 2,4-triazolo [4,3-b] pyridazine; 6- (l-methylene-l, 2,4-triazol-3-ylmethoxy) -7-phenyl-3- (thiophen-2-yl) -J., 2,4-triazolo [4,3- b] pyridazine; 6- (l-metü-líf-l, 2,4-triazol-3-ümetoxi) -7-fenñ-3- (? Iridin-3-ü) -l, 2,4-triazolo [4,3-b ]? iridazine; 6- (2-metñ-2 #-l, 2,4-triazol-3-ylmethoxy) -7-phene-3- (thiophen-2-yl) -l, 2,4-triazolo [4,3-b] ] pyridazine; 6- (2-metü-2tf-l, 2,4-triazol-3-ümethoxy) -7-phene-3- (pyridin-3-ü) -l, 2,4-triazolo [4,3-b] ? iridazine; 3- (furan-3-ü) -6- (l-metul-l-l, 2,4-triazol-3-ümethoxy) -7-phene-l, 2,4-triazolo [4,3-b ] pyridazine; 6- (l-metü-l-l, 2,4-triazol-3-: ñmethoxy) -7-phenyl-3- (thiophen-2-yl) -l, 2,4-triazolo [4,3-b ]? iridazine; 6- (5-methyl-l, 2,4-oxadiazol-3-ymethoxy) -3,7-diphenol-l, 2,4-triazolo [4,3-b] pyridazine; 7-phenyl-3- (thiophen-2-y) -6- (2? -l, 2,4-triazol-3-umethoxy) -l, 2,4-triazolo [4,3-b] pyridazine; 3- (furan-2-y) -6- (l-metñ-l // -1, 2,4-triazol-3-ymetoxy) -7-phenyl-l, 2,4-triazolo [4,3- b] pyridazine; 6- (l-metü-l / -l, 2,4-triazol-3-ümethoxy) -3-fenü-7- (thiophen-3-ü) -l, 2,4-triazolo [4,3-b ] pyridazine; 6- (2-metñ-2 / -l, 2,4-triazol-3-ñmethoxy) -7- (thiophen-3-ü) -l, 2,4-triazolo [4,3-bJ? Iridazine; 3-phene-7- (thiophen-3-y) -6- (2'-l, 2,4-triazol-3-ymetoxy) -l, 2,4-triazolo [4,3-bjpyridazine; 6- (2-metü-2ff-l, 2,4-triazol-3-ümetoxi) -3-fenü-7- (thiophen-2-ü) -l, 2,4-triazolo [4,3-b] pyridazine; 6- (l-metü-l / í-l, 2,4-triazol-3-ümethoxy) -3-fenü-7- (thiophen-2-y) -l, 2,4-triazolo [4,3- bjpiridazine; 7- (furan-2-ü) -6- (2-methan-2 / f-l, 2,4-triazol-3-ümethoxy) -3-phen-1, 2,4-triazolo [4,3-bjpyridazine; 7- (furan-2-ü) -6- (l-metñ-l 7-l, 2,4-triazol-3-ylmethoxy) -3-fenü-l, 2,4-tiiazolo [4,3-bjpiridazine; 6- (3-n? Etü-l, 2,4-oxadiazol-5-yl? Netoxy) -3,7-düerul-l, 2,4-triazolo [4,3-b] pyridazine; 3- (4-fluorophenyl) -6- (1-methan-li-7-l, 2,4-triazol-3-y-methoxy) -7-phene-1, 2,4-thiazolo [4,3-b] pmdazine; 3,7-difenu-6- (2-fluor-l, 2,3-triazole-4-methoxy) -l, 2,4-triazolo [4,3-b-pyridazine; 3,7-diphen-6- (pyrazin-2-ylmethoxy) -l, 2,4-triazolo [4,3-b] pyridazine; 3- (4-methylphenol) -6- (1-methyl-1-l, 2,4-triazole-3-) JS2_ ñ methoxy) -7-fenü-l, 2,4-triazolo [4,3-b] pyridazine; 6- (4-methytdiazol-2-ümethoxy) -3,7-diphen-l, 2,4-triazolo [4,3-b]? Iridazine; 6- (5-methanediazol-2-ymetoxy) -3,7-diphenol-l, 2,4-triazolo [4,3-b] pyridazine; 3,7-diene-6- (pyrirnidin-4-ylmethoxy) -l, 2,4-triazolo [4,3-b]? Iridazine; 3,7-difenu-6- (pyridazin-3-υmethoxy) -l, 2,4-triazolo [4,3-b] pyridazine; 6- (l-metü-l / -l, 2,4-triazol-3-ümethoxy) -7- (morpholin-4-ü) -3- (thiophen-2-y) -l, 2,4-triazolo [4,3-b] pyridazine; 3,7-difenu-6- (thiazol-4-ümethoxy) -l, 2,4-triazolo [4,3-bJ? Iridazine; 6- (5-? NetiHsoxazol-3-ü? Netoxi) -3,7-difenü-l, 2,4-triazolo [4,3-bjpiridazine; 3- (3-fluorophenone) -6- (1-methyl-1, 2,4-triazole-3-methoxy) -7- (morpholin-4-ü) -l, 2,4-triazolo [4,3 ^] pyridazine; 3,7-difenn-6- (pirin idin-2-ymetoxy) -l, 2,4-triazolo [4,3-b] pyridazine; 6- (2-metü-2 f-l, 2,3-t-azozol-4-ymetoxy) -3,7-dü: enü-l, 2,4-triazolo [4,3-b] pyridazine; 7- (1-methydobutyl) -6- (1-methyl-1-p, 2,4-triazol-3-y-methoxy) -3-phenyl-1, 2,4-triazolo [4,3-b] pyridazine; 7-isopropyl-6- (2-methyl-2-α-l, 2,4-triazol-3-ihnetoxy) -3-feβ-l, 2,4-triazolo [4,3-b] pyridazine; 7- / erc-butñ-3- (2-flqorofe?) -6 ^ (l-metü-líT-l, 2,4-triazol-3-ñmethoxy) -l, 2,4-triazolo [4,3- b] pyridazine; 7-ddo? Enñ-3- (4-methoxyenu) -6- (2-metü-2 / l-l, 2,4-triazol-3-methoxy) -l, 2,4-triazolo [4,3- bjpiridazine; 7- (1-metñcidopentü) -6- (l-metñ-l / f-l, 2,4-triazol-3-ümethoxy) -3-fenü-l, 2,4-triazolo [4,3-b] pyridazine; 7- (l-metücyclo) enti) -6- (2-? Net? N-2i7-l, 2,4-triazol-3-ylmethoxy) -3-phen-l, 2,4-triazolo [4,3-b] ] pyridazine; 7-cidopentü-3- (furan-2-y) -6- (2-metñ-2-Yl, 2,4-triazol-3-ümethoxy) -l, 2,4-triazolo [4,3-b] pyridazine; 7-cyclopentyl-3- (furan-2-ü) -6- (l-metñ-l / M, 2,4-triazol-3-ylmethoxy) -l, 2,4-triazolo [4,3-b] pyridazine; 3- (3,7-diphenyl-l, 2,4-triazolo [4,3-b] pyridazin-6-ylmethyl) -l, 2,4-triazole-1-acetonitrile; 7- (l-metücido? Ropñ) -6- (2-metü-2-rl, 2,4-triazol-3-ñmethoxy) -3-fenü-l, 2,4-triazolo [4,3-b] pyridazine; 7- (1-methycidopropa) -6- (1-metha-1-yl, 2,4-triazol-3-ylmethoxy) -3-phen-1, 2,4-triazolo [4,3-b] pyridazine; 3- (3-fluorophenone) -6- (1-methyl-1-phenyl, 2,4-triazol-3-ylmethoxy) -7-phenyl-2,4-triazolo [4,3-b] pyridazine; 7- (1-methylenyl) -6- (3-metüpmdin-2-ümethoxy) -3-phen-1, 2,4-triazolo [4,3-b] pyridazine; 6- (1-methan-1-Y, 2,3-triazol-4-ylmethoxy) -3 ^ -difen-1, 2,4-thiazolo [4,3-b] pmdazine; 3- (5-metütiofen-2-ü) -6- (l-metü-l- -l, 2,4-triazol-3-ümethoxy) -7-phene-l, 2,4-triazolo [4,3 -b-pyridazine; 2- [3- (3,7-difenyl-l, 2,4-triazolo [4,3-b] p dazin-6-ñoximetñ) -l, 2,4-triazol-l-ü] -? ', ? '- dimetnacetamide; 3,7-difenñ-6- [l- (pyridin-2- ñmetüJ-l -l ^^ - triazol-S-ñmetoxiJ-l ^^ - triazolo ^ S- ^ piridazina; 6- (l-benzyl-l / f-l, 2,4-triazol-3-methoxy) -3,7-diphenol, 2,4-triazolo [4,3-b] pyridazine; 2- [5- (3,7-dtphen-1, 2,4-triazolo [4,3-b] pyridazin-6-oxymethylene) -l, 2,4-triazol-1-yl] acetamide; ? '- [2- [3- (3,7-difenyl-l, 2,4-triazolo [4,3-b] pyridazin-6-n-oxymethylene) -l, 2,4-triazole-l-ñ] etü ] -? , iV-dimetuamine; 3,7-difenu-6- (pyrimidin-5-i] met * i) -l, 2,4-triazolo [4,3-b] pyridazine; 6- [l- (2- (morpholin-4-ü) -etü) -l / fl, 2,4-triazol-3-ymetoxy] -3,7-dfenfen-l, 2,4-triazolo [4, 3-b] pyridazine; 6- (2-metñ-2-l, 2,4-triazol-3-ümethoxy) -3-phene-7- (pi? ToHdin-l-ñ) -l, 2,4-triazolo [4,3- b] pyridazine; 7- (5-dorothiophen-2-y) -6- (2-meth-2 // - -l, 2,4-triazol-3-umethoxy) -3-fertü-l, 2,4-triazolo [4 , 3-b] pyridazine; 7- (5-chlorothiophen-2-ü) -6- (1-methyl-1, 2,4-triazole-3-methoxy) -3-phen-1, 2,4-triazolo [4,3- b] pyridazine; 6- (l / 7-benzimidazol-2-ümethoxy) -3- (2,4-difluorophemethyl) -7- (l-methüciclopentin) -l, 2,4-triazolo [4,3-b] pyridazine; 3- (furan-3-y) -6- (2-pmdü) rnet-loxi-7,8,9,10-tetr-hydro-l, 2,4-triazolo [3,4-a] phthalazine; 7-cidobutyl-3-phenyl-6- (prop-2-inoxo) -l, 2,4-triazolo [4,3-b] pyridazine; (7-ddobutyl-3-phen-1, 2,4-thiazolo [4,3-b] pyridazin-6-yl) acetonitide; ? ^ - ^^ - cidobutñ-S-fe -l ^^ - triazolo ^ S-bJp dazin-ó-ñox ^ but ^ -inüJ- V-dimetüamina; and the salts and prodrugs thereof.

8. A compound selected from: 2- [3- (3,7-diphenol-l, 2,4-triazolo [4,3-b]? Iridazm-6-ylnoxyet) -l, 2,4-triazole- l-ü] ethyamine; 3,7-difenü-6- [l- (2 - (? IrroHdin-l-ñ) etü) -l /? - l, 2,4-triazolt-3-methoxy] -l, 2,4-triazolo [4, 3-b] pyridazine; 6- [l- (l-methypiperidin-4-y) -líf-l, 2,4-triazol-3-umethoxy] -3,7-difenyl-l, 2,4-triazolo [4,3-b] ? iridazine; 3,7-difenu-6- [l- (2- (piperazin-1-y) et) rl / fl, 2,4-triazol-3-methoxy] -l, 2,4-triazolo [4,3- b] pyridazine; 7- (l-methücidopentñ) -6- (2-metü-2 / -rl, 2,4-txiazol-3-ümethoxy) -3- (2,4-düluoroferm) -l, 2,4-thiazolo [4 , 3-b] p? Dazine; 7- (ddobut-l-enñ) -6- (2-metü-2 ^ 1,2,4-triazol-3-ümethoxy) -3-fenü-l, 2,4-triazolo [4,3-b] pyridazine; 7- (furan-3-ñ) -6- (l-metü-l ^ -l, 2,4-triazol-3-ümethoxy) -3-phene-l, 2,4-triazolo [4,3-b ] pyridazine; N, N-diethyl-? ^ 6- (l-metü-L -? - l, 2,4-triazol-3-ü ^ 7- (l-metñddopentü) -6- (l-metü-l // -l, 2,4-triazol-3-ymetoxy) -3- (2,4-difluorophenyl) -l, 2,4-triazolo [4,3-b] pyridazine; 7- (1, 1-dimetheprop) - 6- (l-rnetñ-lií-l, 2,4-triazol-3-ylmethoxy) -3-phenyl-l, 2,4-triazolo [4,3-b] pyridazine; 6- (2-metü-2ff -l, 2,4-triazol-3-ümethoxy) -3- (4-fluorofenñ) -7- (thiophene- JL84 3-ñ) -l, 2,4-triazolo [4,3-b] pyridazine; 6- (l-methyl-li? -l, 2,4-triazol-3-ymetoxy) -3- (4-fluorofenñ) -7- (thiophen-3-y) -l, 2,4-triazolo [4 , 3-b] pyridazine; 6- (2-metü-2 fl, 2,4-triazol-3-ymetoxy) -3- (2-fluorofenü) -7- (thiophen-3-ü) -l, 2,4-triazolo [4,3 -b]? iridazine; 3- (2-fluorofeml) -7- (l-methyldclobutyl) -6 ^ (2-methyl-2-l, 2,4-triazol-3-υmethoxy) -l, 2,4-triazolo [4,3- b] pyridazine; 3- (2-fluorofenu) -7- (l-metñddobutü) -6- (l-metü-lií-l, 2,4-triazol-3-ñmethoxy) -l, 2,4-triazolo [4,3- b] pyridazine; 6- (1-methyl-1, 2,4-triazol-3-y-methoxy) -3- (2-fluorophenone) -7- (thiophen-3-yl) -l, 2,4-triazolo [4, 3-b] pyridazine; 8-metü-7- (l-metücidobutñ) -6- (l-metñ-l -l, 2,4-triazol-3-ñmethoxy) -3-fenñ-l, 2,4-triazolo [4,3- bjpiridazine; 8-metñ-7- (l-metücidobutñ) -6- (2-metü-2ff-l, 2,4-triazol-3-ümethoxy) -3-fenül-l, 2,4-triazolo [4,3- b] pyridazine; 6- (l-metü-l / fl, 2,4-triazol-3-ümethoxy) -3-fenü-7- (pyrroHdin-l-ü) -l, 2,4-triazqlo [4,3-b] pyridazine; 7-cidobutne-8-methan-6- (2-methan-2-f-l, 2,4-triazol-3-γ-methoxy) -3-phen-1, 2,4-triazolo [4,3-b-pyridazine; 7-ddobutyl-8-methu-6- (1-methyl-1-l, 2,4-thiazol-3-ylmethoxy) -3-phenyl-1, 2,4-t-azolo [4,3-b-pyridazine; 7- (l-metüddopentñ) -6- (2-metñ-2 / -l, 2,4-triazol-3-ñmethoxy) -3- (2-fluorofenñ) -l, 2,4-triazolo [4,3 -b] pyridazine; 7- (l-metñciclopentñ) -6- (l-metü-lií-l, 2,4-triazol-3-ümethoxy) -3- (2-fluorofenñ) -l, 2,4-triazolo [4,3- b]? iridazine; 7-dclobutñ-6- [4- (2,6-din? Ethyl? Qiorfolto-4-y) but-2-irtyloxy] -3-phen-l, 2,4-triazolo [4,3-b]? Iridazine; and the salts and prodrugs thereof.

9. A pharmaceutical composition comprising a compound of formula I, as defined in claim 1, or a pharmaceutically acceptable salt or prodrug thereof, combined with a pharmaceutically acceptable carrier.

10. Use of a compound of the formula I as defined in claim 1 or a pharmaceutically salt thereof or a prodrug thereof for the manufacture of a medicament for the treatment and / or prevention of anxiety.

11. Use of a compound of the formula I as defined in claim 1 or of a pharmaceutically salt thereof or a prodrug thereof for the manufacture of a medicament for the treatment and / or prevention of seizures.

12. A compound that is a modulator of the benzodiazepine binding site JL85 of the human GABAA receptor, which has a binding affinity (Ki) for the oc3 subunit of the human GABAA receptor of 10 nM or less, which induces a potentiation of at least 40% of the EC20 GABA response in recombinant cell lines stably transfected that express the o3 subunit of the human GABAA receptor and that induces a potentiation, at most 30% of the EC20 GABA response in stably transfected cell lines expressing the subunit to the human GABAA receptor.

13. A compound according to claim 12, which is able to exert its beneficial therapeutic action by oral administration.

14. A pharmaceutical composition comprising a compound according to claim 12 or claim 13, in combination with a pharmaceutically acceptable carrier.

15. A composition according to claim 14, which is adapted for oral administration.

16. Use of a compound according to claim 12 or claim 13, to manufacture a medicament for the treatment and / or prevention of anxiety, practically without sedation.

17. Use of a compound according to claim 12 or claim 13, for manufacturing a medicament for the treatment and / or prevention of seizures.

18. A method for selecting non-sedating anxiogenic compounds, comprising: (1) counting a group of test compounds with (a) a line of stably transfected recombinant cells expressing subunit or 3 of the GABAA receptor human; and (b) a line of stably transfected recombinant cells expressing the subunit to the human GABAA receptor; (2) measuring the potency of the EC20 GABA response induced by each of the test compounds in each of the stably transfected cell lines (a) and (b); and (3) selecting test compounds that induce at least 40% enhancement of the EC20 GABA response in L86 cell line expressing the a3 subunit and at most a 30% enhancement of the EC20 GABA response in the cell line expressing the subunit al.

19. A process for preparing a compound according to claim 1, comprising: (A) reacting a compound of formula III with a compound of formula IV: (III) (IV) wherein Y, Z, R1 and R2 are as defined in claim 1, and L1 represents a suitable protecting group; or (B) reacting a compound of formula VII with a compound of formula VIII: (VII) (VIII) wherein YZ, R1 and R2 are defined as in claim 1, and L3 represents a suitable protecting group; or (C) reacting a compound of formula Z-CO2H with a compound of formula IX: 8Z (IX) wherein Y, Z, R1 and R2 are as defined in claim 1; in the presence of silver nitrate and ammonium persulfate; or (D) reacting a compound of formula X with a compound of formula XI: (X) (XI) wherein Y, Z, R1 and R2 are as defined in claim 1, Alk represents an alkyl group d-6, and L4 represents a suitable protecting group; in the presence of a transition metal catalyst; and (E) if desired, converting a compound of formula I, obtained initially, into another compound of formula I by conventional procedures.