MXPA03005990A

MXPA03005990A - Pharmaceutically active compounds.

Info

Publication number: MXPA03005990A
Application number: MXPA03005990A
Authority: MX
Inventors: Ian Kemp Mark
Original assignee: Pfizer
Priority date: 2001-03-28
Filing date: 2002-03-19
Publication date: 2005-02-14
Also published as: JP2004528320A; EP1395589A1; CA2442329A1; AU2002241211A1; GB0107751D0; BR0208463A; WO2002079203A8; WO2002079203A1

Abstract

Compounds of general formula (1): wherein R1, R2, R3, R4, X, Y and A have the meanings given herein which are useful in the curative and prophylactic treatment of a medical condition for which inhibition of a cyclic guanosine 3 , 5 - monophosphate phosphodiesterase (e.g. cGMP PDE5) is desired.

Description

PHARMACEUTICAL ACTIVE COMPOUNDS FIELD OF THE INVENTION This invention relates to pharmaceutically useful compounds, in particular, to compounds that are useful in the inhibition of cyclic 3 ', 5' -monophosphate of guanosine phosphodiesterases (cGMP PDE), such as 3 ', 5' cyclic guanosine monophosphate phosphodiesterases type 5 (cGMP PDE5). Therefore, the compounds have utility in a variety of therapeutic areas, including male erectile dysfunction (MED). Prior art International patent applications WO 99/24433, WO 99/67244 and WO 01/646777 describe certain 2-phenyl-substituted imidazotriazinone derivatives that inhibit cGMP PDE. DESCRIPTION OF THE INVENTION According to the present invention, there are provided compounds of general formula I: or pharmaceutically or veterinarily acceptable salts, solvates, polymorphs or prodrugs thereof, wherein: A represents CHOH or C = 0; X represents O or NR5; Y represents CH or N; R1 and R2 independently represent H, C, -C6 alkyl, Het, Cj-Ce-Ket alkyl, aryl, C, -C6-aryl, halo-, cyano, nitro, OR6, OC (6) R6, C (0 ) R6, C (0) OR6, NR6C (O) NR7R8, NR6C (0) OR6, OC (0) NRR8, C (0) NR9R10, NR9R10, S02NR9R10 or S02RN; R3, R4 and R5 independently represent H, Cl-C6 alkyl, Het, alkyl C] -C6-Het, aryl or alkyl or R3 and R5, together with the nitrogen atom to which they are attached, can form a heterocyclic ring which is optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12, OC (0) R12, C (0) R12, C (0) 0R12, NR1 C (0) NR13R14, NR12C ( 0) OR12, OC (0) NRI3R14, C (0) NR15R16, NR15R16, S02NR15R16 or S02R17; wherein, when R1, R2, R3, R4 or RS is a C, -C6 alkyl, Het, Ct-C6-Het alkyl, aryl or C [-C6-aryl] alkyl group, such C, -C6 alkyl group, Het, C, -C6-Het alkyl, aryl or C, -C6-aryl alkyl may be optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR6, 0C (0) R6, C (0) R6, C (0) 0R6, NR6C (O) NR7R8, NR5C (0) OR6, 0C (O) NR7R8, C (0) NRR10, NRR10, S02NR9R10, S02Ru, C, -C6 alkyl, Het, alkyl C, -CÓ-Het, aryl or alkyl Cj-Q-aryl; wherein when R1, R2, R3, R4 or R5 is an alkyl group -C6, Het, Ci-C6 alkyl-Het, aryl or C, -C6-alkyl aryl which is substituted and / or terminated with one or more substituents selected from: C, -C6 alkyl, Het, C6 alkyl-Het; aryl or C, -C6-aryl alkyl, such substituent groups are optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12, OC (0) R12, C (0) R12, C (0) OR12; NR12C (O) NRi3R14, NR12C (0) OR12, OC (0) NR13R14, C (O) NR15R16, NR15R16, S02NR15R16 or S02R17; R6, R7 and R3 independently represent H, C] -C6 alkyl, Het, C, -C6-Het alkyl, aryl or C, -C6-aryl alkyl; or R7 and R8, together with the nitrogen atom to which they are attached, can form a heterocyclic ring which is optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12, OC (0) R12, C (0) R12, C (0) OR12, NR12C (0) NR1R14, NRIC (O) OR12, OC (O) NRl3R14, C (0) NR15R16, NRI5R16, S02NRl5R16 or S02R17; R9 and R10 independently represent H, C (0) R6, S02Ru, C, -C6 alkyl, Het, Cj-C6 alkyl-Het, aryl or C, -C6-aryl alkyl; or R9 and R10, together with the nitrogen atom to which they are attached, can form a heterocyclic ring which is optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12, OC (0} R12, C (0) R12, C (0) OR12, NR12C (0) NRI3R14, NR12C (0) OR12, OC (0) NRl3R14, C (0) NR15R16, NR15R16, S02NR15R16 or S02R17; R11 represents C-alkyl , -C6, Het, alkylC ^ Cg-Het, aryl or C, -C6-alkyl, in which, when R6, R7, R8, R9, R1Q or Rn is an alkyl group -C Het, alkyl Ci- C6-Het, aryl or C- [C5-aryl] alkyl, such C6-C6 alkyl group, Het, C, -C6-Het alkyl, aryl or C, -C6-alkyl aryl may be optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12, OC (0) R12, C (0) R12, C (0) OR12, NR, 2C (O) NRI3R1, NR12C (O) OR12, OC ( O) NR, 3R14, C (0) NRI5R16, NRI5R16, S02NRI5R16 or S02R17; R12, R13 and R14 independently represent H or C, -C6 alkyl; or R13 and R14, together with the nitrogen atom to which they are attached, can form a heterocyclic ring; R15 and R16 independently represent H, C (0) R12, S02R17 or C6-C6 alkyl; or R15 and R16, together with the nitrogen atom to which they are attached, can form a heterocyclic ring; R17 represents Cl-C6 alkyl; t wherein Het represents an optionally substituted heterocyclic group of four to twelve members, said group containing one or more heteroatoms selected from nitrogen, oxygen, sulfur and mixtures thereof; with the proviso that when Y is CH, X is O and A is C (O), then each of R1, R3 and R4 does not represent C, -C6 alkyl and R2 does not represent C, -C6 alkyl or C3- cycloalkyl. C6; and with the additional proviso that when Y is CH, X is 0 and A is CH (OH), then each of R1 and R3 does not represent C, -C6 alkyl, and R2 does not represent C, -C6 alkyl or C3 cycloalkyl -C6 and R4 is not phenyl or C, -C5 alkyl optionally substituted with up to 2 substituents selected from hydroxy, phenyl, NR9R10 or 0C (0) R6, where R9 and R10 are H groups, (C, -C6) alkyl, alkyl ( C, -C6) -phenyl or phenyl optionally substituted with hydroxy or OR12 and with R6 being alkyl (?, - Cg) optionally substituted with a halogen or OR12, and OR12 O-alkyl (CrCfi) being compounds referred to together hereinafter as "the compounds of the invention". The term "aryl", when used herein, includes aromatic carbocyclic groups of six to ten members, such as phenyl and naphthyl. The term "Het", when used herein, includes ring systems of four to twelve members, preferably four to ten members, said rings containing one or more heteroatoms selected from nitrogen, oxygen, sulfur and mixtures thereof, and said rings may contain one or more double bonds or may be non-aromatic, partially aromatic or fully aromatic in character. The ring systems can be monocyclic, bicyclic or condensed. Thus, the term includes groups such as azetidinyl, pyrrolidinyl, imidazolyl, indolyl, furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, oxatriazolyl, thiatriazolyl, pyridazinyl, morphoylinyl, pyrimidinyl, pyrazinyl, pyridinyl, quinolinyl, isoquinolinyl, piperidinyl, pyrazolyl, imidazopyridinyl and piperazinyl, optionally substituted. The substitution in Het may be in a carbon atom of the Het ring or, where appropriate, in one or more of the heteroatoms. The "Het" groups may also be in the form of an N-oxide. Preferred Het groups for use herein are 5- to 8-membered ring systems (C5-C8) containing at least one N and optionally 0, S or mixtures thereof. In this document, Het or alkylHet substituents in highly preferred R 1 and / or R 2 are the morpholinyl, piperidinyl, pyrazolyl, imidazolyl, triazolyl, pyridinyl or azetidinyl groups. The heterocyclic ring which may represent R3 and R5, R7 and R8, R9 and R10, R13 and R14 or R15 and R15 (together with the nitrogen atom to which they are attached), may be any heterocyclic ring containing at least one carbon atom. nitrogen and that forms a stable structure when it is bound to the rest of the molecule through the essential nitrogen atom (which, to avoid doubts, is the atom to which R3 and R5, R7 and R8, R9 and R10, R13 respectively are attached) and R14 or R15 and R16). In this regard, heterocyclic rings which may represent R3 and R5, R7 and R8, R9 and R10, R13 and R14 or R15 and R16 (together with the nitrogen atom to which they are attached) include ring systems of four to twelve members , preferably from four to ten members, said rings containing at least one nitrogen atom and optionally containing one or more additional heteroatoms selected from nitrogen, oxygen and / or sulfur, and said rings may contain one or more double bonds or may be non-aromatic character, partially aromatic or totally aromatic. Thus, the term includes groups such as azetidinyl, pyrrolidinyl, imidazolyl, indolyl, triazolyl, tetrazolyl, morpholinyl, piperidinyl, pyrazolyl and piperazinyl. The term "C-C6 alkyl" (which includes the C parte-Cj alkyl part of the C C-C6-C H alkyl groups and alkyl, when used herein, includes the methyl, ethyl, propyl, butyl, pentyl groups and hexyl Unless otherwise specified, alkyl groups, when there is a sufficient number of carbon atoms, may be linear or branched, may be saturated or unsaturated, or may be cyclic, acyclic or partly cyclic and partly Acyclic The preferred C ^ -Q alkyl groups for use herein are C, -C4 alkyl groups.

The alkyl C, -C6-Het and alkyl (-Ce-aryl substituted groups defined hereinbefore, may have substituents on the ring and / or on the alkyl chain.The halo groups with which they can be substituted or terminated groups mentioned above include fluoro, chloro, bromo and iodo The compounds of general formula I are referred to herein as "the compounds of the invention" or "the compounds." A preferred group of compounds according to a further aspect of the invention, are compounds of formula I as defined above, wherein: A represents CHOH or C = 0, X represents 0, Y represents CH or N, R1, R2, R3 and R4 independently represent C1- alkyl; C6, Het, Cj-Cg-Het alkyl, aryl or Cj-Q-aryl alkyl optionally substituted and / or terminated with one or more substituents selected from: halo-, OR6, NR9R10, C-C6 alkyl, Het, Ci alkyl -C6 ~ Het, aryl or Cj-Cg-aryl alkyl, in which when R1, R2, R3 or R4 is a C 1 -C 6 alkyl, Het, alkyl-Cg-Het, aryl or C 1 -C 6 alkyl-aryl group which is substituted and / or terminated with one or more substituents selected from: C 1 -C 6 alkyl, Het, C 6 alkyl C Het , aryl or Ci-C6-aryl alkyl, such substituents are optionally substituted and / or terminated with one or more additional substituents selected from: halo-, OR12 or NR1R16; wherein R6, R9, R10, R12, R13 and R16 are as defined above in this document. > with the proviso that when Y is CH, X is O and A is C (O), then each of R1, R3 and R4 does not represent Ci-C6 alkyl and R2 does not represent Q-Cg alkyl or C3-C6 cycloalkyl, and with the additional proviso that when Y is CH, X is O and A is CH (OH), then each. of R1 and R3 does not represent alkyl Cj-Cg, and R2 does not represent C] -C6 alkyl or C3-C5 cycloalkyl and R4 is not phenyl or Cj-Cs alkyl optionally substituted with up to 2 substituents selected from hydroxy, phenyl, NR9R10 or OC (0) R6, where R9 and R10 are groups H, alkyl (Cj-Cg), alkyl (Cj-Cg) -phenyl or phenyl optionally substituted with hydroxy or OR12 and R6 being (C6) alkyl optionally substituted with a halogen or OR12 , and being OR12 O-alkyl (C, -C6). Especially preferred are compounds as defined above in which Y = CH or N, preferably N, and A = C (O), and R 1 = Cj-Q alkyl or Cj-Q-Het alkyl, preferably C 1 -alkyl. C3-Het, and R2 and R4 are independently selected from Cj-C4 alkyl, preferably C-C3 alkyl and R3 = C ^ -Q alkyl, preferably C2-C4 alkyl, with the Het group being a morpholinyl, piperidinyl, pyrazolyl group, imidazolyl, triazolyl, pyridinyl or azetidinyl, and preferably being morpholinyl or piperidinyl. According to another aspect of the present invention, preferred compounds of general formula (I) are provided, wherein: A represents CHOH or C = 0 X represents O; x Y represents N; R1, R2, R3 and R4 independently represent Cj-Cg alkyl, Het, alkyl C] -C6-Het, aryl or Cj-Q-aryl alkyl optionally substituted and / or terminated with one or more substituents selected from: halo-, OR6, NR9R10, Cj-Cg alkyl, Het, C 1 -Cg-Het alkyl, aryl or C, -C6-aryl alkyl; wherein when R1, R2, R3 or R4 is an alkyl group Cj-Cg, Het, alkyl Cj-Cg-Het, aryl or Cj-Cg-aryl alkyl which is substituted and / or terminated with one or more substituents selected from : CrCl alkyl (Het, alkyl (-? - Cg-Het, aryl or Cj-Cg-aryl alkyl, such substituents are optionally substituted and / or terminated with one or more additional substituents selected from: halo-, OR12 or NR15R½; wherein R6, R9, R10, R12, R15 and R16 are as defined above. According to a further aspect, the present invention provides alternative preferred compounds of general formula (I) as defined above, wherein: A represents C = 0; X represents O or MR5 and preferably is O; Y represents CH or N, and preferably is CH; R1 and R2 independently represent H, Het, alkyl Cj-Q-Het, aryl, Cj-C6-alkyl aryl, halo-, cyano, nitro, OR6, OC (0) R6,, C (0) R6, C (0) ) OR6, NR6C (0) R7R8, NR6C (0) OR6, OC (O) NR7R8, C (0) NR9R10, NR9R10, S02NR9R10 or S02Ru; R 3 or R 4 independently represent H, Het, C 1 -Cg-Het alkyl, aryl or C 1 -Ce-aryl alkyl; R 5 independently represents H, C 1 -C 6 alkyl, Het, C 1 -C 6 alkyl, Het, aryl or C 1 -C 0 alkyl aryl; or R3 and R5, together with the nitrogen atom to which they are attached, can form a heterocyclic ring that is optionally substituted and / or terminated with one or more substituents; selected from: halo-, cyano, nitro, OR12, OC (0) R12, C (0) R12, C (0) 0R12, NR12C (0) NR13R14, NR12C (O) OR12, OC (O) NR14, C ( 0) NR15R16, NR15R16, S02NR15R16 or S02R17 wherein when R1, R2, R3 or R4 is a C] -C3 alkyl group, Het, C ^ Q-Het alkyl, aryl or C ^ -C-alkyl aryl, such group Het, alkyl C] -C6-Het, aryl or C, -C6-alkyl aryl may be optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR6, OC (0) R6, C (0) R6, C (0) OR6, NR6C (0) NR7R8, NR6C (0) OR6, OC (0) NR7R8, C (0) R9R10, NR9R10, S02NR9R10, S02Ru ,. C, -C6 alkyl, Het, alkyl Cj-C6-Het, aryl or Cj-C ^ alkyl-aryl; wherein when R1, R2, R3 or R4 is a Het group, Cj-Q-Het alkyl, aryl or C ^ Q-aryl alkyl that is substituted and / or terminated with one or more substituents selected from: Ci-C6 alkyl , Het, alkyl C ^ -Cg-Het, aryl or alkylC ^ -aryl, such substituent groups are optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12, OC ( ) R12, C (0) R12, C (0) OR12, NR12C (O) NR13RW, NR12C (O) OR12, OC (0) NR13R14, C (0) NR15R16, NR15R16, S02 R15R16 or S02R17; wherein when R5 independently represents a group H, C ^ -C ^ alkyl, Het, alkyl C ^ -C ^ -Het, aryl or Ci-C6 alkyl-aryl, such alkyl group Cj-Cg, Het, alkyl Cj- C6-Het, aryl or C, -C6-aryl alkyl may be optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR6, OC (0) R6, C (0) R6, C (0) OR6, NR6C (O) NR7R8, NR6C (O) OR6, OC (0) R7R8, C (0) NR9R10, NR9R10, S02NR9R10, S02Rn, alkyl Het, aryl or Ci-C6 alkyl-aryl, - in which when R 5 is a C 1 -Cg alkyl, Het, C 1 -C 6 alkyl, Het, aryl or C 1 -C 6 alkyl group which is substituted and / or terminated with one or more substituents selected from: C 1 -C alkyl, Het, alkyl Cj-Cg-Het, aryl or alkyl such substituent groups are optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12, OC (0) R12, C (0) R12 , C (0) OR12, NR12C (O) NR13RM, NR12C (O) OR12, OC (0) NR13R14, C (0) NR15R16, NR15R16, S02NR15R16 or S02R17; Rfi, R7 and R8 independently represent H, Cj-Q alkyl, Het, Cj-C6-Het alkyl, aryl or Ci-C6 alkyl aryl; or R7 and R8, together with the nitrogen atom to which they are attached, can form a heterocyclic ring which is optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12, OC (0) R12, G (0) R12, C (0) OR12, NR, 2C (0) R13R14, R12C (0) OR12, 0C (O) NRI3R14, C (0) NR15R16, NR15R16, S02NR15R16 or S02R17; R9 and R10 independently represent H, C (0) R6, S02Rn, C ^ -Ci alkyl, Het, Cj-C6 alkyl-Het, aryl or C] -C6-alkyl aryl; or R9 and R10, together with the nitrogen atom to which they are attached, can form a heterocyclic ring that is optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12, 0C (0) R12, C (0) R12, C (0) 0R12, NR12C (0) NR13R, TSIR12C (0) OR11, 0C (O) NR13R14, C (0) NR15R16, NR, 5R16, S02 R15R16 or S02R17; R n represents alkyl Cj-Cg, Het, alkyl Ci-C-Het, aryl or C, -C6-aryl alkyl; wherein R6, R7, R8, R9, R10 or R11 is a C ^ Q alkyl group, Het, alkyl, said alkyl groups being C, -C6, Het, Ci-C6 alkyl, Het, aryl or C 1 alkyl; Cg-aryl. optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12, 0C (0) R12, C (0) R12, C (0) 0R12, NR12C (O) NRi3R14, NR12C (O ) OR12, 0C (O) NR13R14, C (0) NR15R16, NR15R16, S02NR15R16 or S02R17; R12, R13 and R14 independently represent H or C, -C6 alkyl; or R13 and R14, together with the nitrogen atom to which they are attached, can form a heterocyclic ring; R15 and R16 independently represent H, C (0) R12, S02R17 or alkyl ^ -Cf; or R15 and R16, together with the nitrogen atom to which they are attached, can form a heterocyclic ring; R17 represents alkyl -Ce; wherein Het represents an optionally substituted four- or twelve-membered heterocyclic group, said group containing one or more heteroatoms selected from nitrogen, oxygen, sulfur and mixtures thereof. According to another aspect of the present invention, alternative preferred compounds of general formula (I) are provided as defined above, wherein: A represents CH (OH); X represents O or NR5 and preferably is O; Y represents CH or N and preferably is CH; R1 and R2 independently represent H, Het, C 1 -Cg-Het alkyl, aryl, Cj-Cg-aryl alkyl, halo-, cyano, nitro, OR6, OC (0) R6, C (0) R6, C (0) OR6, NRSC (0) OR5, 0C (O) NR7R8, C (0) NR9R10, NR9R10, S02 R9R10 or S02RH; R 3 represents H, Hetr alkyl C! -C6-Het, aryl or C 1 Q-aryl alkyl; R 4 represents H, Het or C 1 Cg-Het alkyl; R 5 independently represents H, C 1 alkyl, Het, C 1 -C 6 alkyl, Het, aryl or C 1 -C 6 alkyl aryl; or 3 and R5, together with the nitrogen atom to which they are attached, can form a heterocyclic ring that is optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12, OC (0) R12, C (0) R12, C (0) OR12, NR12C (0) NR13R14, R12C (O) OR12, OC (0) NR13RM, C (0) NR15R16, NR15R16, S02 R15R16 or S02R17; wherein when R1, R2 or R3 is a Cj-C6 alkyl, Het, Ci-Cg-Het alkyl, aryl or C 1 -Cg-aryl alkyl group, such a Het group, C, -C 6 -Het alkyl, aryl or C] -C6 alkyl aryl may be optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR6, OC (0) R6 / C (0) R6, C (0) OR6, NR6C (0) NR7Rs, NR6C (0) OR6, OC (0) NR7R8, C (0) NR9R10, NR9R10, S02NR9R10, S02Rn, C, -C6 alkyl, Het, > alkyl -Cg-Het, aryl or Cj-Cg-aryl alkyl; wherein when R1, R2 or R3 is a group Het, alkyl C) -C6-Het, aryl or C, -C6-alkyl aryl which is substituted and / or terminated with one or more substituents selected from: alkyl QQ, Het , Cj-Cg-Het alkyl, aryl or C [-C6-aryl] alkyl, such substituent groups are optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12, OC (0) R12 , C (0) R12, C (0) OR12, R12C (O) RI3RM, NR12C (O) OR12, OC (0) NR13R14, C (0) NR15R16, NR15R15, S02NR15R16 or S02R17; wherein when R4 is a Het group or alkyl Cj-Cg-Het, such a Het or alkyl-Ce-Het group may be optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR6 , OC (0) R6, C (0) R6, C (0) OR6, NR6C (0) NR7R8, NR6C (0) 0R6, OC (0) NR7R8, C (0) NR9R10, NR9R10, S02NR¾10, S02Rn, alkyl d ~ C6, Het, C 1 -Cg-Het alkyl, aryl or Cj-Cg-aryl alkyl; wherein when R4 is a Het group or Cj-C6-Het alkyl which is substituted and / or terminated with one or more substituents selected from: C ^ Cg alkyl, Het, Cj-C5-alkyl, aryl or Cj-alkyl Q-aryl, such substituent groups are optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12, OC (0) R12, C (0) R12, C (0) OR12, R , 2C (O) NR13R14, NR12C (O) OR12, OC (O) NR13R14, C (0) NR15R16, NR15R16, S02NRI5R16 or S02R17; wherein when R5 independently represents a group H, Ci-C6 alkyl, Het, alkyl Cj-C6-Het, aryl or alkyl dQ-aryl, such C-C6 alkyl group, Het, alkyl Gj-C6-Het, aryl or C6-aryl alkyl may be optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR6, OC (0) R6, C (0) R6, C (0) OR6, NR6C ( O) NR7R8, NReC (0) OR6, OC (0) NR7R8, C (0) NR9R10, NR9R10, S02 R9R10, S02Ru, alkyl dQ, Het, alkyl dC6-Het, aryl or alkyl C! -C6-aryl wherein when R5 is an alkyl group Cj-Cg, Het, alkyl d-C6-Het, aryl or alkyl d-Cg-aryl that is substituted and / or terminated with one or more substituents selected from: Cj-Ce alkyl, Het, alkyl C, -Ce-Het, aryl or alkyl d-C6-aryl, such substituent groups are optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12, OC (0) R12, C (0) R12, C (0) OR12, NR12C (O) NR13R14, NR12C (O) OR12, OC (O) NR13R14, C (0) NR15R16, R15R15, S02NR15R 16 or S02R17; R6, R7 and R8 independently represent H, alkyl -C ^, Het, C ^ -Cg-Het alkyl, aryl or CrC6-alkyl aryl; or R7 and R8, together with the nitrogen atom to which they are attached, can form a heterocyclic ring which is optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12, OC (0) R12, C (0) R12, C (0) OR12, NR12C (0) NR13R14, NR12C (0) OR12, 0C (0) R13Ru, C ()) NR15R16, NR15R16, S02NR15R16 or S (¾R17; R9 and R10 represent independently H, C (0) R6, S02Ru, alkyl -Cg, Het, alkylC ^ -Cg-Het, aryl or alkyl Cj-Q-aryl or R9 and R10, together with the nitrogen atom to which they are attached, can forming a heterocyclic ring which is optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12, 0C (0) R12, C (0) R12, C (0) 0R12, NR12C (0 ) NR! 3R! 4, NR12C (O) OR12, OC (O) NR13R14, C (0) NR15R16, R1R16, S02NRl5R16 or S02R17; Ru represents C ^ -Cg alkyl, Het, C, -C6-Het alkyl, aryl or Ci-C6 alkyl aryl; wherein when R6, R7, R8, R9, R10 or R11 is an alkyl group Cj-Cg, Het, alkyl Cj-Cg-Het, aryl or alkyl such a C, -C6 alkyl, Het, Ci-C6 alkyl group Het, aryl or C] -C6-alkyl aryl may be optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12, 0C (0) R12, C (0) R12, C ( 0) 0R12, NR12C (O) RI3R14, R12C (0) OR12, 0C (O) NR13R14, C (0) NR15R16, NR15R16, S02NR15R16 or S02R17, - R12, R13 and R14 independently represent H or C, -C6 alkyl; or 13 and R14, together with the nitrogen atom to which they are attached, can form a heterocyclic ring; R15 and R16 independently represent H, C (0) R12, S02R17 or Cx-C6 alkyl; or R15 and R16, together with the nitrogen atom to which they are attached, can form a heterocyclic ring; R17 represents Cj-C6 alkyl; wherein Het represents an optionally substituted heterocyclic group of four to twelve members, said group containing one or more heteroatoms selected from nitrogen, oxygen, sulfur and mixtures thereof. According to another additional aspect, the present invention provides compounds of general formula (I): or pharmaceutically or veterinarily acceptable salts, solvates, polymorphs or prodrugs thereof, wherein: A represents CHOH or C = 0; X represents O or NR5; Y represents CH or N; R1 and R2 independently represent H, C, -C6 alkyl / Het, C, -C6-Het alkyl, aryl, C, -C6-aryl, halo-, cyano, nitro, OR6, OC (0) R6, C ( 0) R6, C (0) OR6, R6C (O) R7R8, R6C (O) OR6, OC (0) R7R8, C (0) R9R10, NRR10, S02NR9R10 or S02RH; R3, R4 and R5 independently represent H, C] -C6 alkyl, Het, Ci-C6 alkyl-Het, aryl or alkyl-C-aryl; or R3 and R5, together with the nitrogen atom to which they are attached, can form an etherocyclic ring which is optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12, OC (0) R12, C (0) R12, C (0) OR12, NR12C (0) NR13R14, NR12C (O) OR12, OC (O) NR13R14, C (0) NR15R16, NR15Rlfi, S02NR15R16 O SOjR17; wherein when R1, R2, R3, R4 or R5 is a CX-C6 alkyl group, Het, Ci-C5 alkyl Het, aryl or alkyl-Ce-aryl, such alkyl group Cj-C6, Het, alkyl C ^ -Cg-Het, aryl or C, -C6-aryl alkyl may be optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR6, OC (0) R6, C (0) R5 , C (0) OR6, NR6C (0) NR7R8, NRsC (0) 0R6, OC (0) NR7R8, C (0) NR9R10, NR9R10, S02NR9R10, S02Ru, CX-C6 alkyl, Het, alkyl (Cg-Het, aryl or Ci-Cg-aryl alkyl wherein when R1, R2, R3, R4 or R5 is a Ci-Cg alkyl, Het, C C-C6 alkyl, Het, aryl or C, -C6-aryl alkyl group that is substituted and / or terminated with one or more substituents selected from: Cj-C8 alkyl, Het, alkyl (VC6-Het, aryl or Cj-Ce-aryl alkyl, such substituent groups are optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12, 0C (0) R12, C (0) R12, C (0) 0R12, R12C (O) NR13R14, NR12C (0) OR12, OC (0) NR13R14, C ( 0) NR15R16, R15R16, S02 R15R16 or S02R17; R6, R7 and R8 independently represent H, Cj-Cg alkyl, Het, C, -C6-Het alkyl, aryl or Cj-Cg-aryl alkyl or R7 and R8, together with the nitrogen atom to which they are attached, can form a heterocyclic ring that is optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12, 0C (0) R12, C (0) R12, C (0) 0R12, NR12C (0) NR13R14, NR12C (0) OR12, 0C (0) NR13R14, C (0) RI5R16, NR15R15, S02NR15R16 or S02R17; R9 and R10 independently represent H, C (0) R6, S02Ru, Ci-C6 alkyl, Het, C ^ -Q-Het alkyl, aryl or Cj-Cg-aryl alkyl; or R9 and R10, together with the nitrogen atom to which they are attached, can form a heterocyclic ring that is optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12, 0C (0) R12, C (0) R12, C (0) 0R12, NR2C (0) NR13R14, R12C (O) OR12, 0C (O) R13R14, C (0) NR15R16, NR15R16, S02NR15R16 or S02R17; Ru represents C, -C6 alkyl, Het, Cj-Cg-Het alkyl, aryl or Cx-Cg-aryl alkyl; wherein when R6, R7, R8, R9, R10 or R11 is a Ci-C6 alkyl group, Het, alkyl Cj-Q-Het, aryl or Cj-Q-aryl alkyl, such Ct-C6 alkyl group, Het, alkyl Cj-Cg-Het, aryl or Cj-Cg-aryl alkyl may be optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12, 0C (0) R12, C (0) R12, C (0) 0R12, R12C (O) NR13R14, NR12C (O) OR12, 0C (O) NR13R14, C (0) NR15R16, NRI5R16, S02 R15R16 or S02R17; R12, R13 and R14 independently represent H or C -C6 alkyl or R and Ri4 ^ together with the nitrogen atom to which they are attached, can form a heterocyclic ring; R15 and R16 independently represent H, C (0) R12, S02R17 or Ct-C6 alkyl; or R15 and R16, together with the nitrogen atom to which they are attached, can form a heterocyclic ring, -R17 represents Ci-C6 alkyl and Het represents an optionally substituted four to twelve-membered heterocyclic group, said group containing one or more heteroatoms selected from nitrogen, oxygen, sulfur and mixtures thereof. The pharmaceutically or veterinarily acceptable salts of the compounds containing a basic center are, for example, addition salts of non-toxic acids formed with inorganic acids such as hydrochloric, hydrobromic, iodohydric, sulfuric and phosphoric acids, with carboxylic acids or with organosulfonic acids. Examples include the salts HC1, HBr, HI, sulfate or bisulfate, nitrate, phosphate or phosphate acid, acetate, benzoate, succinate, saccharate, fumarate, maleate, lactate, citrate, tartrate, gluconate, camsylate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate and pamoate. The compounds of the invention can also provide pharmaceutically or veterinarily acceptable metal salts, in particular, non-toxic salts of alkali and alkaline earth metals, with bases. Examples include the sodium, potassium, aluminum, calcium, magnesium, zinc and diethanolamine salts. As a review of pharmaceutically acceptable salts, see Berge et al., J. Pharm, Sci. , 66, 1-19, 1977. The pharmaceutically acceptable solvates of the compounds include the hydrates thereof. Various salts of the compounds and polymorphs thereof are also included within the scope of this invention. When a compound contains one or more asymmetric carbon atoms, it exists in two or more stereoisomeric forms. When a compound contains an alkenyl or alkenylene group, cis (E) and trans (Z) isomerism can also be produced. The present invention includes the individual stereoisomers of the compounds and, where appropriate, their individual tautomeric forms, together with mixtures thereof. The separation of the diastereoisomers or cis and trans isomers can be achieved by conventional techniques, for example, by fractional crystallization, chromatography or H.P.L.C. of a stereoisomeric mixture of a compound of formula (I) or of a suitable salt or derivative thereof. An individual enantiomer of a compound can also be prepared from a corresponding optically pure intermediate, or by resolution, such as by H.P.L.C. of the corresponding racemate using a suitable chiral support, or by fractional crystallization of the diastereomeric salts formed by reaction of the corresponding racemate with a suitable optically active acid or base, as appropriate. All stereoisomers of the compounds are included within the scope of this invention.

The compounds may exhibit tautomeria. All tautomeric forms of the compounds, and mixtures thereof, are included within the scope of this invention. Derivatives of the compounds labeled with radioisotopes, which are suitable for biological studies, are also included within the scope of the application. Preparation In accordance with another aspect of the invention, methods are provided for the preparation of the compounds of the invention, as illustrated below. The following procedures are illustrative of the general synthetic procedures that can be adopted to obtain the compounds of the invention: 1. The compounds of formula I can be prepared by cyclization of a corresponding compound of formula II: wherein R1, R2, R3, R4, X, Y and A are as previously defined for the compounds of formula I, for example, under conditions known to those skilled in the art. Such conditions include reaction, at a temperature between room temperature and reflux temperature, in the presence of a suitable dehydrating agent (Lewis acid) (e.g., phosphorus oxychloride) and an appropriate solvent (e.g. -dichloroethane), or as otherwise described in the prior art. The compounds of formula II can be prepared by the reaction of corresponding compounds of formula III: wherein R17 represents Cg alkyl, and R1 and R2 are as previously defined for the compounds of formula II, with compounds of formula IV: or a suitable acid addition salt thereof (eg, a hydrochloride salt), wherein R3, R4, X, Y and A are as previously defined for the compounds of formula II, for example, under conditions known to those skilled in the art. Such conditions include, for example, the reaction at a temperature between room temperature and reflux temperature (eg, 70 ° C), in the presence of a suitable solvent (eg, ethanol, diethyl ether, 1,4- dioxane or N, N ~ dimethylformamide). The compounds of formula III can be prepared by conventional techniques, for example, by decarboxylation of the corresponding compounds of formula V: wherein R1, R2 and R17 are as previously defined for the compounds of formula III, for example, under conditions known to those skilled in the art. Such conditions include, for example, the reaction at an elevated temperature (for example, at reflux temperature), in the presence of a suitable solvent (for example, methanol or ethanol) and, optionally, in the presence of a suitable base (for example, example, sodium hydrogen carbonate). The compounds of formula V can be prepared by the reaction of corresponding compounds of formula VI: wherein R and R2 are as previously defined for compounds of formula V, with compounds of formula VII: wherein R17 is as previously defined for the compounds of formula V, and L1 is a leaving group such as halo-, preferably chloro, for example, under conditions known to those skilled in the art. Such conditions include the reaction, at a temperature between room temperature and reflux temperature, in the presence of a suitable organic solvent (for example, THF or ether), an appropriate base (e.g., pyridine, sodium hydride, tertiary potassium butoxide, lithium diisopropylamide, piperidine or triethylamine), optionally in the presence of a suitable catalyst (for example, 4- (dimethylamino) pyridine) and, optionally, with the previous conversion of VI into 1,3-oxazole-5 (4H ) -one with an excess of VII (reaction of Dakinest). Alternatively, compounds of formula III can be prepared by reaction of the corresponding compounds of formula VIII: wherein R1, R2 and R17 are as previously defined for the compounds of formula III, with ozone in an oxygen stream, followed by reduction of the resulting ozonide, for example, for the two steps, under conditions known to those skilled in the art. Conditions for ozonation include, for example, the reaction at a temperature below room temperature (eg, -70 ° C), in the presence of a suitable solvent (for example, dichloromethane). Conditions for reducing the intermediate ozonide include, for example, the reaction at a temperature below room temperature (eg, -70 ° C), with a suitable reducing agent (eg, dimethyl sulfide), followed by treatment (at the same temperature) with an appropriate base (for example, pyridine). The compounds of formula VIII can be prepared by the reaction of corresponding compounds of formula IX: wherein L2 represents a suitable leaving group (e.g., -N (CH3) OCH3 or chloro) and R1 and R2 are as previously defined for the compounds of formula VIII, with a compound of formula X: wherein M represents H or a suitable metal-containing moiety (eg, Na, Li, g (II) halide, or a cuprate) and R is as previously defined for compounds of formula VIII, eg, in conditions known to those skilled in the art. Such conditions include, for example, the reaction of a compound of formula IX at a temperature between -80 ° C and room temperature, in the presence of a suitable solvent (for example, THF), with a mixture formed by the reaction, at a temperature below room temperature (for example, r78 ° C), of a compound of formula X in which M represents H (for example, ethyl vinyl ether), a suitable organolithium reagent (for example, tert-butyl) -litium), an appropriate solvent (e.g., THF) and, optionally, a source of a suitable metal salt (e.g., diethyl etherate of MgBr2). The compounds of formula IX can be prepared from corresponding compounds of formula VI, as defined hereinabove, under conditions known to those skilled in the art. Alternatively, the compounds of formula III can be prepared by reaction of corresponding compounds of formula XI: wherein R1, R2 and R17 are as previously defined for the compounds of formula III, with an oxidizing agent (for example, Dess-Martin periodinane) at a temperature between -78 ° C and the reflux temperature in a suitable solvent (eg, DCM). The compounds of formula XI can be prepared by the reaction of compounds of formula XII: wherein R1 and R2 are as previously defined for compounds of formula XI, with HCl ^ in R17OH, where R17 is as previously defined for compounds of formula XI, at a temperature between -10 ° C and 20 ° C, followed by the reaction with an aqueous base (for example, 10% Na 2 CO 3 solution) at a temperature between 20 ° C and the reflux temperature. The compounds of formula XII can be prepared by reaction of compounds of formula XIII: O H XIII wherein R1 and R2 are as previously defined for compounds of formula XII, with a source of cyanide (eg, acetone cyanohydrin), in a suitable solvent (eg, DCM), optionally in the presence of a base (for example, Et3iJ), at a temperature between 0 ° C and the reflux temperature. The compounds of formula XIII can be prepared by the reaction of compounds of formula XIV: wherein R1 and R2 are as previously defined for compounds of formula XIII, with a hydride source (e.g., LiAlH4) in a suitable solvent (e.g., THF) at a temperature between about -78 ° C and 20 ° C. The compounds of formula XIV can be prepared from compounds of formula VI using conditions known to those skilled in the art. The compounds of formula IV can be prepared by conventional techniques, for example, by reaction of the corresponding compounds of formula XV: or an acid addition salt thereof (eg, a hydrochloride salt), wherein R3, R4, X, Y and A are as previously defined for the compounds of formula IV, with hydrazine, for example, in conditions known to those skilled in the art. Such conditions include, for example, the reaction at a temperature between -10 ° C and room temperature, in the presence of a suitable solvent (for example, a Cj-C3 alcohol), or as described otherwise in the art. previous In a particular embodiment, a compound of formula IV is formed in situ by reaction at a temperature between a low temperature and room temperature (eg, from -10 ° C to 25 ° C) of a compound of formula XV with hydrate of hydrazine in an alcoholic solution. This is continued by the addition of a compound of formula III, after which the mixture is brought to reflux, finally producing a compound of formula II. The compounds of formula XV can be prepared from corresponding compounds of formula XVI which, in turn, can be prepared from compounds of formula XVII which, in turn, can be prepared from compounds of formula XVIII, using known conditions for the specialists in the technique: The conditions suitable for the transformation into amide of acid XVIII in the corresponding amide compound XVII, and for the subsequent dehydration reaction to prepare the nitrile compound XVI from compound XVII, and for the addition of ammonia or the formation reaction of amidine from compound XVI to obtain compound XV will be known to the skilled chemist.

Alternatively, the compounds of formula IV can be prepared by reaction of the compounds of formula XIX: wherein A,?, X, R3 and R4 are as previously defined for the compounds of formula IV, with hydrazine in a suitable solvent (for example, THF), at a temperature between 20 ° C and the reflux temperature . The compounds of formula XIX can be prepared by reaction of the compounds of formula XX: wherein A, X, Y, R3 and R4 are as previously defined for compounds of formula XIX, with a methylating agent (eg, iodomethane) in a suitable solvent (eg, acetone), at a temperature between 20 ° C and the reflux temperature. The compounds of formula XX can be prepared by reaction of the compounds of formula XVII with La esson reagent in a suitable solvent (for example, toluene), at a temperature between 20 ° C and the reflux temperature. The compounds of formula XVIII, wherein Y represents CH and A represents C = 0, can be prepared from the corresponding compounds of formula XXI: wherein X and R3 are as previously defined for the compounds of formula XVIII, using the Friedel-Craf s acylation reaction. Typical conditions are to use CIC (0) R4, where R4 is as previously defined for compounds of formula XVIII, (from 1 to 3 equivalents) and, optionally, a Lewis acid (eg, from 2 to 10 equivalents of A1C13) in an organic solvent (for example, dichloromethane), at a temperature between 0 ° C and the reflux temperature. Alternatively, the compounds of formula XVIII can be prepared from the corresponding compounds of formula XXII: wherein R3, X and Y are as previously defined for the compounds of formula XVIII and Hal represents chloro-, bromo- or iodo-, by conversion of Hal into AR4. This can be achieved by means of any of the routes indicated below: .. (a) the so-called "Heck" conditions (eg, 2 equivalents of a source of an acyl anion equivalent (such as butyl vinyl ether), 1.7 equivalents of Et3N and catalytic amounts of Pd (0Ac) 2 and P ( o-tol) 3, in eCN at a temperature between room temperature and reflux temperature). When a Heck reaction is carried out on an alkyl alkenyl ether, products will be obtained in which A represents C = 0. Such reactions are not suitable when R 4 is aryl; or (b) the so-called "Sonogashira" conditions (for example, as described in Synthesis, 1980, 8, 627) such as from 1.5 to 5 equivalents of a terminal alkyne and from 0.024 to 0.03 equivalents of Pd ( PPh3) 2C12 / Cul, in Et3N and MeCN at a temperature between room temperature and 60 ° C), followed by hydrolysis of the resulting alkyne (typical conditions, 0.3 equivalents of HgS04, H2S04, acetone at reflux). It should be noted that this procedure will give products in which A represents C = 0. Such reactions are not suitable when R 4 is aryl; or halogen / lithium exchange followed by inactivation in acyl chloride (to give products where A represents C = 0). Alternatively, the anion can be inactivated in an aldehyde to give products in which A represents CHOH. Then, this alcohol can be reoxidized to the corresponding ketone using conventional oxidizing agents such as manganese dioxide. The preferred conditions for the. Acyl chloride reaction are: 1 to 2 equivalents of n-butyl lithium, and 1 to 2 equivalents of R 4 CO 1 in THP, at a temperature of about -78 ° C at about room temperature. If, for example, RC0C1 is LCH2C0C1 (where L is a leaving group such as methanesulfonate, p-toluenesulfonate or halo-, preferably chloro- or bromo-), then, once the above procedure is carried out, the product can be further functionalized by displacement of L with a nucleophile (for example, a primary or secondary amine); o Formation of a Grignard reagent or a cincate by the addition of magnesium or a zinc source (eg, zinc, zinc chloride, Reike zinc), followed by inactivation in an acyl chloride (giving products where A represents C = 0). Alternatively, the Grignard or zinc reagent can be inactivated in an aldehyde to give products in which A represents CHOH. Again, the alcohol formed can be oxidized, giving the required ketone as detailed above in this document; or Carbonylation to produce a carboxylic acid, an ester or an amide of einreb. Preferred conditions are: CO (344,737 kPa), Pd (OAc) 2 (0.03 equivalents), 1,1'-bis (diphenylphosphino) ferrocene (0.045 equivalents), triethylamine (5 equivalents) and a suitable nucleophile (e.g. , alcohol, amine), at a temperature of 40 to about 80 ° C. Alternatively, the Weinreb amine can be synthesized from the carboxylic acid and the aldehyde can be synthesized from the ester or the carboxylic acid. The acid chloride can be formed from the carboxylic acid. Preferred conditions for forming acid chloride from the acid are: (COCl) 2 (1.2 equivalents),?,? - dimethylformamide (one drop) in dichloromethane. Then, a nucleophile such as a Grxgnard reagent or a cincate with the ester, Weinreb amide or acid chloride can be reacted, yielding products in which A represents C = 0. Alternatively, analogous reactions with the aldehyde would produce products in which A represents CHOH. Preferred conditions for the addition of Grignard reagent to the acid chloride are: R gBr (1 equivalent) and Fe (acac) 3 (0.03 equivalents) in THF. The compounds of formula XXII can be prepared by halogenation of the corresponding compounds of formula XXIII: XXIII wherein X, Y and R3 are as previously defined for the compounds of formula XXII, by conventional techniques. These include iodination with N-iodosuccinimide (1 to 2 equivalents) in a 4: 1 mixture of trifluoroacetic acid and trifluoroacetic anhydride at a temperature between room temperature and reflux temperature (suitable when Y represents N). These conventional techniques also include bromination with bromine in DCM at temperatures between room temperature and reflux temperature (suitable when Y represents CH). 2. Alternatively, the compounds of formula I can be prepared from the corresponding compounds of formula XXIV: (f) wherein R1, R2, R3, X and Y are as previously defined for the compounds of formula I, and Hal represents chloro-, bromo- or iodo-, by conversion of Hal to AR4. This can be achieved using the conditions described hereinabove for the synthesis of compounds of formula XVIII from compounds of formula XXII. The compounds of formula XXIV can be prepared by cyclization of the corresponding compounds of formula XXV: wherein R1, R2, R3, X, Y and Hal are as previously defined for the compounds of formula XXIV, using the conditions described hereinabove for the synthesis of the compounds of formula I from compounds of formula II. The compounds of formula XXV can be prepared by reaction of the corresponding compounds of formula XXVI: wherein R3, X, Y and Hal are as "have been previously defined for compounds of formula XXV, with a compound of formula III, for example, using the conditions described hereinabove for the synthesis of compounds of formula II from compounds of formulas III and IV The compounds of formula XXVI can be prepared from the corresponding compounds of formula XXVII using the procedure described above for the preparation of compounds of formula IV from compounds of formula XV.

XXVII The compounds of formula XXVII can be prepared from the corresponding compounds of formula XXVIII which, in turn, can be prepared from compounds of formula XXIX which, in turn, can be prepared from compounds of formula XXII using known conditions for the specialists in the technique: The conditions suitable for the amide conversion of compound XXII to compound XXIX, and for the dehydration reaction to prepare compound XXVIII from compound XXIX, and for the addition of ammonia or the amidine formation reaction to pass the compound XXVIII to compound XXVII, will be well known to the expert chemist. Alternatively, compounds of formula XXVI can be prepared from the corresponding compounds of formula XXX: wherein Y, X, Hal and R3 are as defined above for the compounds of formula XXVI, with hydrazine in a suitable solvent (for example, THF), at a temperature between 20 ° C and the reflux temperature. The compounds of formula XXX can be prepared by reaction of compounds of formula XXXI: wherein X, Y, Hal and R3 are as defined above for compounds of formula XXX, with a methylating agent (for example, iodomethane) in a suitable solvent (for example, acetone), at a temperature of 20 ° C and the reflux temperature. The compounds of formula XXXI can be prepared by reaction of the corresponding compounds of formula XXXII: XXXII wherein X,?, Hal and R3 are as previously defined for the compounds of formula XXXI, with La esson reagent in a suitable solvent (for example, toluene), at a temperature between 20 ° C and the temperature of Reflux. The compounds of formula XXXII can be prepared from the corresponding compounds of formula XXII by methods known to those skilled in the art. 3. Alternatively, the compounds of formula I can be prepared from the corresponding compounds of formula XXXIII: XXXIII wherein R1, R2, R3, X and Y are as previously defined for the compounds of formula I, by functionalization in the alpha position with respect to methyl ketone. This procedure is not applicable to the compounds of formula I in which R 4 represents aryl or Het. Examples of functionalization in the alpha position with respect to methyl ketone include halogenation, preferably bromination, to form alpha-halo ketones; or oxidation to form alpha-hydroxy ketones. These ketones functionalized in the alpha position can be converted to other compounds of formula I using procedures known to those skilled in the art (e.g., displacement of the halogen by a suitable nucleophile such as a primary or secondary amine, or conversion of the alcohol to an ether using the Mitsunobu reaction). Preferred conditions for bromination are 1.1 equivalents of N-bromosuccinitide and 3 equivalents of triflic acid in dichloromethane. Alternatively, the addition of a base to compounds of formula XXXIII will form the corresponding enolates, which can then be inactivated in a suitable electrophile (for example, an alkyl halide). Typical conditions for this transformation are 1.1 to 2 equivalents of a suitable base (e.g., LDA, NaH) and 1.1 to 2 equivalents of the suitable electrophile (e.g., alkyl halides) in THF or ether. The compounds of formula XXXIII can be prepared by the process described for the preparation of compounds of formula I in process 1. Alternatively, compounds of formula XXXIII can be prepared from the corresponding compounds of formula XXIV using the conditions defined above in this document for the preparation of compounds of formula I from compounds of formula XXIV. 4. Alternatively, the compounds of formula I (wherein Y represents CH) can be prepared from the corresponding compounds of formula XXXIV: XXXIV wherein R1, R2, R3 and X are as previously defined for the compounds of formula I, using the Friedel-Crafts acylation reaction. Typical conditions are to use an acyl chloride (from 1 to 3 equivalents) and, optionally, a Lewis acid (for example, from 2 to 10 equivalents of A1C13) in an organic solvent (for example, dichloromethane) at a temperature between 0 ° C and the reflux temperature. The compounds of formula XXXIV can be prepared by cyclization of the corresponding compounds of formula XXXV: wherein R1, -R2, R3 and X are as previously defined for the compounds of formula XXXIV, using the conditions described above for the synthesis of compounds of formula I from compounds of formula II. The compounds of formula XXXV can be prepared by the reaction of corresponding compounds of formula XXXVI: where R3. and X are as previously defined for compounds of formula XXXV, with a compound of formula III, for example, using the conditions described hereinabove for the synthesis of compounds of formula II from compounds of formulas III and IV . The compounds of formula XXXVI can be prepared from corresponding compounds of formula XXXVII using the procedure described above for the preparation of compounds of formula IV from compounds of formula XV: Compounds of formula XXXVII can be prepared from corresponding compounds of formula XXXVIII which, in turn, can be prepared from compounds of formula XXXIX which, in turn, can be prepared from compounds of formula XXI, using known conditions for the specialists in the technique: XXXVIII XXXIX The conditions suitable for the amide conversion of compound XXI to compound XXXIX, and for the dehydration reaction to prepare compound XXXVIII from compound XXXIX, and for the addition of ammonia or the amidine formation reaction to pass compound XXXVIII to compound XXXVII will be known to the skilled chemist. Alternatively, compounds of formula XXXVI can be prepared from the corresponding compounds of formula XXXX: xxxx wherein X and R3 are as previously defined for the compounds of formula XXXVI, with drazine in a suitable solvent (for example, THF), at a temperature between 20 ° C and the reflux temperature. The compounds of formula XXXX can be prepared by reaction of compounds of formula XXXXI: XXXXI wherein X and R3 are as previously defined for the compounds of formula XXXX, with a methylating agent (for example, iodomethane) in a suitable solvent (for example, acetone), at a temperature between 20 ° C and reflow temperature. The compounds of formula XXXXI can be prepared by reaction of the corresponding compounds of formula XXXIX with Lawesson's reagent in a suitable solvent (for example, toluene), at a temperature between about 20 ° C and the reflux temperature. The compounds of formula XXXIX can be prepared from the corresponding compounds of formula XXIII by methods known to those skilled in the art. Compounds of formulas VI, VII, IX, X, XXI, XXIII and their derivatives, when not available commercially or not described below, can be obtained by a method analogous to the procedures described hereinbefore or by synthetic methods conventional, in accordance with conventional techniques, from readily available starting materials, using the appropriate reagents and reaction conditions. When X represents O, R3 can be changed to an alternative R3 group (R3a) at any stage and in any of the methods described hereinbefore, by reaction of the appropriate intermediate with R3a0H and a base (eg, cesium carbonate) to the reflux temperature (or, if carried out in an airtight container, at a temperature above the reflux temperature). Similarly, when X represents O, OR3 can be changed to R3R5 at any stage and in any of the methods described hereinabove, by reaction of the appropriate intermediate with H R5, optionally in the presence of catalytic copper sulfate, at temperatures between the ambient temperature and the reflux temperature (or, if carried out in an airtight container, at a temperature above the reflux temperature). The compounds in which A represents CHOH can be prepared at any step and in any of the methods described hereinabove from the corresponding compounds in which A represents C = 0. This transformation can be achieved by using a suitable reducing agent, preferably sodium borohydride in methanol. Similarly, compounds in which A represents C = 0 can be prepared at any step and in any of the methods described hereinabove from the corresponding compounds in which A represents CHOH. This transformation can be achieved using a suitable oxidizing agent (for example, manganese dioxide). The compounds of the invention can be isolated from their reaction mixtures using conventional techniques. Those skilled in the art will appreciate that, in the course of working up the procedures described above, the functional groups of the intermediates may need to be protected by protecting groups.

The functional groups that it is desirable to protect include idroxy-, amino- and carboxylic acid. Suitable protecting groups for the hydroxy- include trialkylsilyl and diarylalkysilyl groups (for example, tert-butyldimethylsilyl, tert-butyldiphenylsilyl or trimethylsilyl), and tetrahydropyranyl and allylcarbonyl groups (for example, methyl- and ethylcarbonyl). Suitable protecting groups for the amino include tert-butyloxycarbonyl, 9-f 1 -oreni-1-t-oxy-arbonyl or benzyloxycarbonyl. Suitable protecting groups for the carboxylic acid include alkyl or benzyl esters. The protection and deprotection of the functional groups can be carried out before or after any of the reaction steps described hereinabove. The protecting groups can be removed according to techniques that are well known to those skilled in the art. Protection / deprotection strategies may be employed as appropriate, such as those known in the literature.

Protective groups suitable for use according to the invention can be found in "Protecting Groups" edited by P.J. Kocienski, Thieme, New York, (1994); and in "Protective Groups in Organic Synthesis", 2nd edition, TW Greene & P.G.M. Wutz, Wiley-Interscience (1991). Those skilled in the art will also appreciate that, in order to obtain compounds of formula I in an alternative manner and, on some occasions, more conveniently, the individual steps of the process mentioned hereinabove may be performed in a different order, and / or the reactions Individuals may be performed at a different stage in the overall route (i.e. substituents may be added - and / or chemical transformations may be performed on different intermediates to those mentioned earlier herein in relation to a particular reaction). This will depend, among other things, on factors such as the nature of other functional groups present in a particular substrate, the availability of key intermediates and the strategy of protective groups (if applicable) to be adopted. Clearly, the type of chemistry involved > it will influence the choice of reagent used in said synthetic steps, the need and type of protective groups that are used, and in the sequence to perform the synthesis. The pharmaceutically acceptable acid addition salts of the compounds of formula I containing a basic center can be prepared in a conventional manner. For example, a solution of the free base can be treated with the appropriate acid, either neat or in a suitable solvent, and the resulting salt can then be isolated by filtration or by flash evaporation of the reaction solvent. The pharmaceutically acceptable base addition salts can be obtained in an analogous manner by treating a solution of a compound of formula I with the appropriate base. The two types of salts can be formed or interconverted using ion exchange resin techniques. The present invention also includes all suitable isotopic variations of a compound of formula (I) or a pharmaceutically acceptable salt thereof. An isotopic variation of a compound of formula (I) or a pharmaceutically acceptable salt thereof is defined as a variation in which at least one atom is replaced by an atom having the same atomic number but an atomic mass different from the mass atomic normally found in nature. Examples of isotopes that can be incorporated into the compounds of formula (I) and pharmaceutically acceptable salts thereof include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus--, sulfur, fluorine and chlorine, such as 2H, 3H , 13C, 14C, 15N, 170, 180, 31P, 32P, 35S, I8F and 36C1, respectively. Certain isotopic variations of the compounds of formula (I) and pharmaceutically acceptable salts thereof, for example, those in which a radioactive isotope such as 3H or 14C is incorporated, are useful in studies of tissue distribution of drugs and / or substrates. Particularly preferred are the isotopes tritium, i.e., 3H, and carbon-14, i.e., 1C, for their ease of preparation and detectability. In addition, substitution with isotopes such as deuterium, i.e., 2H, can produce certain therapeutic advantages due to greater metabolic stability, for example, a longer half-life in vivo or the need for reduced doses and, therefore, can be preferred in some circumstances The isotopic variations of the compounds of formula (I) and pharmaceutically acceptable salts thereof of this invention can generally be prepared by conventional procedures such as the illustrative procedures or by the preparations described in the Examples and Preparations shown hereinafter. , using the appropriate isotopic variations of the appropriate reagents. Those skilled in the art will appreciate that certain protected derivatives of the compounds of formula (I), which can be obtained before a final deprotection phase, may not possess pharmacological activity as such, but, in certain cases, may be administered orally or parenterally and subsequently metabolized in the body to form compounds of the invention that are pharmacologically active. Therefore, such derivatives can be described as "prodrugs". In addition, certain compounds of formula (I) can act as prodrugs of other compounds of formula (I). All protected and prodrug derivatives of the compounds of formula (I) are included within the scope of the invention. Examples of suitable prodrugs for the compounds of the present invention are described in Drugs of Today, Volume 19, Number 9, 1983, pages 499-538.; in Topics in Chemistry, Chapter 31, pages 306-316; and in "Design of Prodrugs" by H. Bundgaard, Elsevier, 1985, Chapter 1 (whose descriptions are incorporated herein by reference).

In addition, those skilled in the art will appreciate that certain remains, known to those skilled in the art as "prorests", for example, as described by H. Bundgaard in "Design of Prodrugs" (the description of which is incorporated herein by reference). ) can be put on appropriate functionalities when such functionalities are present within the compounds of formula (I). Preferred prodrugs for the compounds of formula (I) include: alcohols, esters, carbonate esters, half esters, phosphate esters, nitro esters, sulfate esters, sulfoxides, amides, carbamates, azo compounds, phosphamides, glycosides, ethers, acetals and ketals. The present invention further comprises the combination of an inhibitor compound of the G Pc PDE5 as defined above, which combination can be administered by sequential, simultaneous or joint administration of a compound with: (1) one or more natural or synthetic prostaglandins or esters thereof. Prostaglandins suitable for use in this invention include compounds such as alprostadil, prostaglandin Elf prostaglandin E0, 13,14-dihydroprostaglandin Ex, prostaglandin E2, eprostinol, natural, synthetic, semi-synthetic prostaglandins and derivatives thereof, including those described in US 6037346 issued March 14, 2000 and incorporated herein by reference, PGE0, PGEj, PGAj, PGBj, GFi a, 19-hydroxy-PGA, 19-hydroxy-PGBlf PGE2, PGB2, 19-hydroxy-PGA2 , 19-hydroxy-PGB2, PGE3a, carboprost, tromethamine dinoprost, tromethamine, dinoprostone, lipoprost, gemeprost, metenoprost, sulprostune, tiaprost and moxisylate; and / or one or more α-blockers or α-adrenergic receptor antagonist compounds, also known as α-adrenoceptors, α-receptors. Compounds suitable for use in this invention include: α-adrenergic receptor blockers such as those described in PCT application WO99 / 30697 published June 14, 1998, the description of which refers to α-adrenergic receptor blockers, is incorporated herein by reference, and includes selective adrenoceptor or a2-adrenoceptor blocking agents and non-selective adrenoceptor blocking agents. Suitable α-α-adrenoceptor blockers include: phentolamine, phentolamine mesylate, trazodone, alfuzosin, indoramin, naftopidyl, tamsulosin, dapiprazole, phenoxybenzamine, idazoxan, efaroxan, yohimbine, rauwolfia alkaloids, Recorda i 15/2739, SNAP 1069, SNAP 5089, RS17053, SL 89.0591, doxazosin, terazosin, abanoquil and prazosin; α2-blockers from US 6037346 [March 14, 2000] dibenarnine, tolazoline, trimazosin α-adrenergic receptor blockers such as those described in US Pat Nos: 4188390; 4026894; 3511836; 4315007; 3527761; 3997666; ' 2503059; 4703063; 3381009; 4252721 and 2599000, each of which is incorporated herein by reference; α2-adrenoceptor blockers include: clonidine, papaverine, papaverine hydrochloride, optionally in the presence of a cardiotonic agent such as proxamine; and / or (3) one or more NO donor compounds (NO agonists). NO donor compounds suitable for use in this invention include organic nitrates such as mono-, di- or trinitrates or organic nitrate esters, including glyceryl binitrate (also known as nitroglycerin), isosorbide 5-mononitrate, isosorbide dinitrate, pentaerythritol tetranitrate, erythrityl tetranitrate, sodium nitroprusside (SNP), 3- morpholinosidnonimine, molsidomine, S-nitroso-N-acetyl penicillamine (SNAP), S-nitroso-N-glutathione (SNO-GLU), N-hydroxy-L -aginine, amyl nitrate, linsidomine, linsidomine hydrochloride, (SIN-1) S-nitroso-N-cysteine, diazenium diolate, (NONOates), 1,5-pentanedinitrate, L-arginine, ginseng, zizphi fructus, molsidomine, Re-2047, nitrosolated derivatives of maxisylyte such as N I-678-11 and NMI-937 as described in PCT application publication WO 0012075; and / or (4) one or more potassium channel opening agents. Potassium channel opening agents suitable for use in this invention include nicorandil, cromakalim, levcromakalim, lemakalim, pinacidil, cliazoxide, minoxidil, charibdotoxin, glyburide, 4-aminopyridine, BaCl2; and / or (5) one or more dopaminergic agents, preferably apomorphine or a selective agonist of D2, D3 or D2 / D3 such as pramipexole and ropyrinol (as claimed in WO 0023056), L-Dopa or carbidopa, PNU S5666 (as claimed in WO 00 40226); and / or (6) one or more vasodilating agents. Vasodilating agents suitable for use in this invention include nimodepine, pinacidil, cycllandelate, isoxsuprine, chloropromazine, haloperidol, Rec 15/2739, trazodone; I (7) one or more thromboxane A2 agonists and / or (8) one or more ergot alkaloids in U.S. Patent No. 6,037,346, issued March 14, 2000, ergot alkaloids are described suitable rye and include acetergamine, brazergoline, bromerguride, cianergoline, delorgotrile, dysulergine, ergonovine maleate, ergotamine tartrate, etisulergine, lergotrile, lisergide, mesulergine, metergoline, metergotamine, nicergoline, pergolide, propisergide, proterguride, terguride; and / or (9) one or more compounds that modulate the action of atrial natriuretic factor (also known as atrial natriuretic peptide), natriuretic factors of type B and C such as inhibitors of neutral endopeptidase; I (10) one or more compounds that inhibit the angiotensin converting enzyme such as enlaapril, and one or more combined inhibitors of angiotensin converting enzyme and neutral endopeptidase such as omapatrilate; and / or (11) one or more angiotensin receptor antagonists such as losartan; and / or (12) one or more substrates for NO-synthase, such as L-arginine; and / or (13) one or more calcium channel blockers such as amlodipine; and / or (14) one or more endothelin receptor antagonists and inhibitors of the endothelin-converting enzyme; I (15) one or more cholesterol lowering agents such as statins (e.g., atorvastatin / Lipitor-trademark) and fibrates; and / or (16) one or more antiplatelet and antithrombotic agents; for example, tPA, uPA, arfarine, hirudins and other thrombin inhibitors, heparin, is inhibited by thromboplastin activation factor; and / or (17) one or more insulin sensitizing agents such as rezulin and hypoglycemic agents such as glipizide; I (18) one or more COX 2 inhibitors; and / or (19) pregabalene; and / or (20) gabapentene; and / or (21) one or more acetylcholinesterase inhibitors such as donezepil; and / or (22) one or more steroidal anti-inflammatory agents; I (23) one or more estrogen agonists and / or estrogen antagonists, preferably raloxifene or lasofoxifene, (-) - cis-6-phenyl-5- [4- (2-pyrrolidin-1-yl-ethoxy) -phenyl] 5,6,7,8-tetrahydronaphthalene-2-ol and the pharmaceutically acceptable salts thereof (compound K shown below), the preparation of which is detailed in WO 96/21656.

Compound A (24) one or more of an additional PDE inhibitor, more particularly an inhibitor of PDE 2, 4, 7 or 8, preferably a PDE2 inhibitor, said inhibitors preferably having an IC50 against the respective enzyme of less than lOOnM; and / or (25) one or more of an NPY inhibitor (neuropeptide Y), more particularly an inhibitor of NPY1 or of NPY5, preferably an inhibitor of NPY1, preferably having said NPY inhibitors (including NPY Yl and NPY Y5) a IC50 less than 100 nM, more preferably less than 50 nM; EP-A-1097718 discloses NPY inhibiting compounds and, in particular, suitable NPY1; and / or (26) one or more vasoactive intestinal peptides (VIP), VI mimetics, more particularly mediated by one or more of the subtypes of VIP receptors, VPAC1, VPAC or PACAP (peptide activator of pituitary adenylate cyclase), one or more than one VIP receptor agonist, a VIP analogue (eg, Ro-125-1553) or a VIP fragment, one or more of an α-adrenoceptor antagonist in combination with VIP (for example, Invicorp, Aviptadil); and / or (27) one or more of a melanocortin receptor agonist or a melanocortin modulator or enhancer, such as melatonan II, PT-14, PT-141 or the compounds claimed in WO-09964002, WO-00074679 , WO-09955679, WO-00105401, WO-00058361, WO-00114879, WO-00113112, WO-09954358; and / or (28) one or more of an agonist, antagonist or modulator of the serotonin receptor, more particularly agonists, antagonists or modulators for 5HT1A receptors (including VML 670), 5HT2A, 5HT2C, 5HT3 and / or 5HT6, including those described in WO-09902159, WO-00002550 and / or WO-00028993; and / or (29) one or more of a modulator of the noradrenaline, dopamine and / or serotonin transporters, such as bupropion, GV3-320659; and / or (30) one or more of an agonist and / or purinergic receptor modulator; and / or (31) one or more of a neurokinin receptor (NK) antagonist, including those described in WO-09964008; and / or (32) one or more of an opioid receptor agonist, antagonist or modulator, preferably agonists for the ORL-1 receptor; and / or (33) one or more of an oxytocin / vasopressin receptor agonist or modulator, preferably a selective oxytocin agonist or modulator; and / or (34) one or more modulators of cannabinoid receptors; I (35) one or more of a NEP inhibitor, preferably said NEP EC 3.4.24.11 and, more preferably, said NEP inhibitor being a selective inhibitor for EC 3.4.24.11, more preferably with the selective NEP inhibitor being a selective inhibitor for CE 3.4.24.11 which has an IC50 less than 100 nM- (e.g., omapatrilate or sampatrilat); EP-A-1097719 discloses suitable NEP inhibitor compounds; and / or (36) one or more compounds that inhibit the angiotensin converting enzyme such as enalapril, and one or more combined inhibitors of angiotensin converting enzyme and neutral endopeptidase such as omapatrilate; and / or (37) one or more tricyclic antidepressants, for example, amitriptyline; and / or (38) one or more non-steroidal anti-inflammatory agents; and / or (39) one or more angiotensin converting enzyme (ACE) inhibitors, for example, quinapril; and / or (40) one or more antidepressants (such as clomipramine and SSRIs) (such as paroxetine and sertraline). said combination being in the form of co-administration, simultaneous administration, concurrent administration or administration by stages. Medical Use The compounds of the invention are useful because they possess pharmacological activity in animals, especially mammals, including humans. Therefore, they are indicated as pharmaceutical agents, as well as for use as medicaments for animals. According to another aspect of the invention, the compounds of the invention are provided for use as pharmaceutical agents and for use as animal medicaments. In particular, it has been found that the compounds of the invention are potent and selective inhibitors of cGMP PDE, such as cGMP PDE5, for example, as demonstrated in the assays described below and, therefore, are useful in the treatment of medical conditions in humans and animals, where inhibition of cGMP PDE is desirable, such as cGMP PDE5. By the term "treatment", the present applicants include both therapeutic (curative), palliative or prophylactic treatment. In this way, according to. Another aspect of the invention provides the use of the compounds of the invention in the manufacture of a medicament for the treatment of a medical condition in which a cGMP PDE inhibitor is indicated (e.g., cGMP PDE5). In addition, the use of the compounds of the invention is provided in the manufacture of a medicament for the treatment of a medical condition in which the inhibition of cGMP PDE (e.g., of cGMP PDE5) is desirable. Thus, it is expected that the compounds of the invention will be useful for the curative, palliative or prophylactic treatment of sexual disorders in mammals. In particular, the compounds are valuable in the treatment of sexual dysfunctions of mammals such as male erectile dysfunction (MED), impotence, female sexual dysfunction (FSD), clitoral dysfunction, female hypoactive sexual desire disorder, sexual arousal disorder female, female sexual pain disorderfemale sexual orgasmic dysfunction (FSOD) as well as sexual dysfunction due to spinal cord injuries or sexual dysfunction induced by a selective serotonin reuptake inhibitor (SSRI), but, clearly, they will also be useful for the treatment of other medical conditions for which is indicated a potent and selective inhibitor of cGMP PDE5. Such conditions include premature delivery, dysmenorrhea, benign prostatic hyperplasia (BPH), obstruction of bladder outlet, incontinence, stable angina, unstable and variant (Prinzmetal), hypertension, pulmonary hypertension, chronic obstructive pulmonary disease, artery disease coronary artery disease, congestive heart failure, atherosclerosis, reduced blood vessel potency states, for example, after post-cutaneous transluminal coronary angioplasty (post-PTCA), peripheral vascular disease, stroke, nitrate-induced tolerance, bronchitis, allergic asthma chronic asthma, allergic rhinitis, diseases and conditions of the eye such as glaucoma, optic neuropathy, macular degeneration, elevated infraocular pressure, retinal or arterial occlusion and diseases characterized by disorders of bowel motility, for example, irritable bowel syndrome ( IBS) x Other medical conditions for to which a potent and selective inhibitor of cGMP PDE5 is indicated, and for which treatment with compounds of the present invention may be useful include preeclampsia, Kawasaki syndrome, nitrate tolerance, multiple sclerosis, diabetic nephropathy, neuropathy, including autonomic and peripheral neuropathy and, in particular, diabetic neuropathy and its symptoms (for example, gastroparesis), peripheral diabetic neuropathy, Alzheimer's disease, acute respiratory failure, psoriasis, skin necrosis, cancer, metastasis, baldness, nutcracker esophagus, anal fissure, hemorrhoids, hypoxic vasoconstriction, diabetes, type 2 diabetes mellitus, insulin resistance syndrome, insulin resistance, reduced glucose tolerance, as well as stabilization of blood pressure during the emodiálisis. Particularly preferred conditions include MED and FSD. In this way, the invention provides a method of treating or preventing a medical condition for which an inhibitor of G Pc PDE5 is indicated, in an animal (e.g., a mammal, including a human), which comprises administering an amount Therapeutically effective of a compound of the invention to a mammal in need of such treatment. Pharmaceutical preparations The compounds of the invention will normally be administered orally or by any parenteral route, in the form of pharmaceutical preparations comprising the active ingredient, optionally in the form of a non-toxic, organic or inorganic acid or base addition salt, in a pharmaceutically acceptable dosage form. Depending on the disorder and the patient to be treated, as well as the route of administration, the compositions may be administered at varying doses. The compounds of the invention can also be combined with any other drug useful in the inhibition of cGMP-PDE, such as GMPC-PDE5. The compounds, their pharmaceutically acceptable salts and the pharmaceutically acceptable solvates of any entity can be administered alone but, in human therapy, will generally be administered in admixture with a suitable excipient, diluent or pharmaceutical carrier selected with respect to the desired route of administration and the conventional pharmaceutical practice.

For example, the compounds or salts or solvates thereof can be administered orally, buccally or sublingually, in the form of tablets, capsules (including soft gel capsules), ovules, elixirs, solutions or suspensions, which may contain flavoring agents or dyes, for applications of immediate, delayed, modified or controlled release, such as sustained, dual or pulsatile. The compounds can also be administered by intracavernous injection. The compounds can also be administered by means of rapidly dispersing or rapidly dissolving dosage forms. Such tablets may contain excipients such as microcrystalline cellulose, lactose, sodium citrate, calcium carbonate, dibasic calcium phosphate, glycine and starch (preferably corn starch, potato or tapioca), disintegrants such as sodium starch glycolate, croscarmellose sodium and certain complex silicates, and granulation binders such as polyvinylpyrrolidone, hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC), sucrose, gelatin and gum arabic. In addition, lubricating agents such as magnesium stearate, stearic acid, glyceryl behenate and talc may be included. Solid compositions of a similar type can also be employed as excipients in gelatin capsules. Preferred excipients in this regard include lactose, starch, cellulose, milk sugar or high molecular weight polyethylene glycols. For aqueous suspensions and / or elixirs, the compounds of the invention may be combined with various sweetening or flavoring agents, coloring materials or dyes, with emulsifying and / or suspending agents and with diluents such as water, ethanol, propylene glycol and glycerin, and combinations thereof. The modified release and pulsatile release dosage forms may contain excipients such as those detailed for immediate release dosage forms, together with additional excipients that act as release rate modifiers, these being coated and / or included in the delivery. body of the device. Release rate modifiers include, but are not limited to, hydroxypropylmethylcellulose, methylcellulose, sodium carboxymethylcellulose, ethylcellulose, cellulose acetate, poly (ethylene oxide), xanthan gum, carbomer, ammonium and methacrylate copolymer, castor oil hydrogenated, carnauba wax, paraffin wax, cellulose acetate phthalate, hydroxypropylmethylcellulose phthalate, methacrylic acid copolymer and mixtures thereof. The modified release and pulsatile release dosage forms may contain one or a combination of excipients modifying the rate of release. The release rate modifying excipients may be present within the dosage form, ie, within the matrix, and / or on the dosage form, for example, on the surface or the coating. The dispersion or rapid dissolution (FDDF) dosage formulations may contain the following ingredients: aspartame, acesulfame potassium, citric acid, croscarmellose sodium, crospovidone, diascorbic acid, ethyl acrylate, ethylcellulose, gelatin, hydroxypropylmethylcellulose, magnesium stearate, mannitol, methyl methacrylate, mint flavorant, polyethylene glycol, non-volatile silica, silicon dioxide, sodium starch glycolate, sodium stearyl fumarate, sorbitol and xylitol. The terms dispersion or dissolution, as used herein to describe FDDF, depend on the solubility of the drug used, ie, when the drug is insoluble, a rapid dispersion dosage form can be prepared, and when the drug is soluble a rapid dissolution dosage form can be prepared. The compounds of the invention may also be administered parenterally, for example, intracavernous, intravenous, intraarterial, intraperitoneal, intrathecal, intraventricular, intraurethral, intrasternal, intracranial, intramuscular or subcutaneous, or they may be administered by infusion techniques. For such parenteral administration, they are best used in the form of a sterile aqueous solution which may contain other substances, for example, enough salts or glucose to make the solution isotonic with the blood. The aqueous solutions should be buffered conveniently (preferably at a pH of 3 to 9), if necessary. The preparation of suitable parenteral formulations under sterile conditions is easily accomplished by conventional pharmaceutical techniques well known to those skilled in the art. For oral and parenteral administration to human patients, the daily dosage level of the compounds of the invention or the salts or solvates thereof will normally be from 10 to 500 mg (in a single dose or in divided doses). Thus, for example, the tablets or capsules of the compounds of the invention, or the salts or solvates thereof, may contain from 5 mg to 250 mg of active compound for single administration or of two or more units of a once, as appropriate. In any case, the doctor will determine the most appropriate actual dose for any individual patient, and this will vary with the age, weight and response of the particular patient. The above doses are illustrative of the middle case. Of course, there may be individual cases in which higher or lower dosing intervals are required, and such ranges are within the scope of this invention. The skilled person will also appreciate that, in the treatment of certain conditions (including MED and FSD), the compounds can be taken as a single dose on a "when required" basis (ie, when needed or desired). Example of Tablet Formulation In general, a tablet formulation typically may contain between about 0.01 mg and 500 mg of the compound (or a salt thereof), while the loading weights of the tablets may vary from 50 mg to 1000. mg. An exemplary formulation for a 10 mg tablet is illustrated: Ingredient% w / w Compound "active" 10,000 * Lactose S4,125 Starch 21,375 Croscarmellose sodium 3,000 Magnesium stearate 1,500 * This amount is typically adjusted according to the activity of the drug. . Such tablets can be manufactured by conventional methods, for example, by direct compression or by a wet or dry granulation process. The cores of the tablets can be coated with appropriate coatings.

The compounds of the invention may also be administered intranasally or by inhalation and are conveniently released in the form of a dry powder inhaler or an aerosol spray presentation from a pressure vessel, pump, sprayer or nebulizer, with the use of a suitable propellant, for example, dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, a hydrofluoroalkane such as 1,1,1,2-tetrafluoroethane (HFA 134A [trademark] or 1,1,1,2,3,3,3-heptafluoropropane (HFA 227EA [trademark]), carbon dioxide or other suitable gas In the case of a pressurized aerosol, the dosing unit can be determined by providing a valve to release a measured quantity.The pressure vessel, pump, sprayer or nebulizer can containing a solution or suspension of the active compound, for example, using a mixture of ethanol and the propellant as solvent, which may additionally contain a lubricant, for example, sorbitan ioleate. Capsules and cartridges (made, for example, from gelatin) for use in an inhaler or insufflator can be formulated so as to contain a powder mixture of the compound of the invention and a suitable powder base such as lactose or starch. The aerosol or dry powder formulations are preferably arranged such that each metered dose or "burst" contains from 1 to 50 mg of compound for release to the patient. The overall daily dose with an aerosol will be in the range of 1 to 50 mg, which can be administered in a single dose or, more usually, in divided doses throughout the day. The compounds can also be formulated for release by means of an atomizer. The formulations for the atomizing devices may contain the following ingredients as solubilizers, emulsifiers or suspending agents: water, ethanol, glycerol, propylene glycol, low molecular weight polyethylene glycols, sodium chloride, fluorocarbons, polyethylene glycol ethers, sorbitan trioleate and oleic acid. Alternatively, the compounds or salts or solvates thereof may be administered in the form of a suppository or a vaginal ovule, or they may be applied topically in the form of a gel, hydrogel, lotion, solution, cream, ointment or fine powder. The compounds or the salts or solvates thereof can also be administered dermally. The compounds or salts or solvates thereof can also be administered transdermally, for example, by the use of a skin patch. They can also be administered through the eye, lung or rectal route. For ophthalmic use, the compounds can be formulated in the form of micronized suspensions in isotonic, sterile, pH-adjusted saline or, preferably, in the form of solutions in isotonic, sterile, pH adjusted saline, optionally in combination with a preservative such as benzalkonium chloride. Alternatively, they can be formulated in an ointment such as petrolatum. For topical application to the skin, the compounds or salts or solvates thereof may be formulated as a suitable ointment containing the active compound suspended or dissolved in, for example, a mixture with one or more of the following: mineral oil, liquid petrolatum, white petrolatum, propylene glycol, polyoxyethylene and polyoxypropylene compound, emulsifying wax and water. Alternatively, they can be formulated as a suitable lotion or cream, or suspended or dissolved in, for example, a mixture of one or more of the following: mineral oil, sorbitan monostearate, a polyethylene glycol, liquid paraffin, polysorbate 60, cetyl wax esters, cetearyl alcohol, 2-octyldodecanol, benzyl alcohol and water. The compounds can also be used in combination with a cyclodextrin. It is known that cyclodextrins form inclusion complexes and complexes that are not inclusion with drug molecules. The formation of a drug-cyclodextrin complex can modify the solubility properties, the rate of dissolution, the bioavailability and / or the stability of a drug molecule. F rmaco-cyclodextrin complexes are generally useful for most dosage forms and routes of administration. As an alternative to the direct formation of complexes with the drug, the cyclodextrin can be used as an auxiliary additive, for example, as a carrier, diluent or solubilizer. The most commonly used cyclodextrins are alpha, beta and gamma cyclodextrins, and suitable examples are described in WO-A-91/11172, WO-A-94/02518 and WO-A-98/55148. In general, in humans, oral administration of the compounds is the preferred route, being the most convenient and, for example in the MED, avoiding the well-known drawbacks associated with intracavernosal administration (i.c.). A preferred oral dosage regimen in the MED for a typical man is 25 to 250 mg of compound when. is required In circumstances in which the recipient suffers a disorder that prevents him from swallowing or can not absorb the drug after oral administration, the drug can be administered parenterally, sublingually or buccally.

For veterinary use, a compound, or a veterinarily acceptable salt thereof, or a solvate or veterinarily acceptable prodrug thereof, is administered as a suitably acceptable formulation in accordance with normal veterinary practice and the veterinarian will determine the dosage regimen and route of administration more appropriate for a particular animal. Thus, in accordance with another aspect, a pharmaceutical formulation is provided which includes a compound as detailed above in admixture with an adjuvant, diluent or pharmaceutically or veterinarily acceptable carrier. In addition to the fact that the compounds inhibit the 3 ', 5'-cyclic guanosine phosphodiesterase monophosphate (cGMP PDE) and, in particular, are potent and selective inhibitors of cGMP PDB5, the compounds may also have the advantage of being more effective or less toxic, have a broader range of activity, be more potent, produce fewer side effects, be absorbed more easily, or have other useful pharmacological properties, with respect to the compounds known in the prior art. The biological activities of the compounds were determined by the following test procedures. Inhibitory Activity of Phosphodiesterase (PDE) The compounds of the present invention are potent and selective inhibitors of cGMP PDE5. The in vitro inhibitory activities of PDE against the 3 ', 5' -cyclic guanosine monophosphate (cGMP) phosphodiesterases and the 3 ', 5'-cyclic adenosine monophosphate (cAMP) phosphodiesterases were determined by measuring their IC50 values (the concentration of compound necessary for 50% inhibition of enzymatic activity). The required PDE enzymes were isolated from a variety of sources, including human cavernous bodies, human platelets, human cardiac ventricle, human skeletal muscle and human and canine retina, essentially by the procedure of W. J. Thompson and M.M. Appleman (Biochem. ', 1971, 10, 311). In particular, cGMP-specific PDE (PDE5) and cAMP PDE inhibited by cGMP (PDE3) were obtained from human cavernous body tissue or human platelets; the PDE stimulated by cGMP (PDE2) was obtained from human cavernous bodies or human platelets; calcium / calmodulin-dependent PDE (Ca / CAM) (PDE1) from human cardiac ventricle; cAMP-specific PDE (PDE4) from a recombinant clone or human skeletal muscle; and the photoreceptor PDE (PDE6) from human or canine retina. Phosphodiesterases 7-11 were generated from full length human recombinant clones transfected in SF9 cells. The tests were performed using a modification of the "discontinuous" procedure of W.J. Thompson et al. . { Biochem. , 1979, 18., 5228) or using a scintillation proximity assay for the direct detection of AMP / GMP using a modification of the protocol described by Amersham foot with product code TRKQ7090 / 7100. In summary, the effect of the PDE inhibitors was investigated by assaying a fixed amount of enzyme in the presence of varying concentrations of inhibitor and a low substrate content (cGMP or cAMP in a 3: 1 ratio of unlabeled to [3H] ] at a concentration ~ 1/2 KJ such that the IC 50 = K 1. The final assay volume was brought to 102 μ? with assay buffer [20 mM Tris-HCl, pH 7.4, 5 mM MgCl 2, 1 mg / ml bovine serum albumin.] Reactions were initiated with enzyme, incubated for 30-60 minutes at 30 ° C to provide <30% substrate renewal and terminated with 50 μ? Of silica silicate SPA beads. yttrium (containing a 3 mM concentration of the respective unlabeled cyclic nucleotide for PDEs 3, 9 and 11) The plates were hermetically sealed and shaken for 20 minutes, after which the beads were allowed to settle for 30 minutes. minutes in the dark and then counted in a TopC plate reader ount (Packard, Meriden, CT). The radioactivity units were converted to% activity of an uninhibited control (100%), plotted against the inhibitor concentration, and the IC50 values of the inhibitor were obtained using the Microsoft Excel extension "Fit Curve" or a equivalent. The results of these tests demonstrate that the compounds of the present invention are potent and selective inhibitors of cGMP-specific PDE5. Metabolism in vitro In vitro metabolism experiments were performed on human hepatic microsomal fractions. Human liver tissue suitable for transplantation was obtained from the International Institute for the Advancement of Medicine (Exton, PA, USA). The microsomes were prepared according to the procedure described in Biochemical Pharmacology, 1966, 48, 2147-2156 and stored at -80 ° C. Protein and cytochrome P450 concentrations were determined by standard procedures described in JOurnal of Biological Chemistry, 1951, 193, 265-275 and Journal of Biological Chemistry, 1964, 239, 2370-2378. Microsomal incubations (1.5 ml) containing 0.5 μM cytochrome P450, 200 mM phosphate buffer (pH 7.4), 0.1 M MgCl2, 0.1 M isocitric acid, 1 unit / ml isocitrate were prepared dehydrogenase and ß-NADP 20 Mm. The compounds under study were added after a 5 minute preincubation at 37 ° C providing an initial substrate concentration of 1 μ ?. The mixture was incubated at 37 ° C and samples (100 μ?) Were removed for analysis for a period of up to 60 minutes. The metabolism in the samples was terminated by the addition of NaOH (0.1 M) containing an internal standard (chosen for having physicochemical properties similar to the compounds under study), followed by extraction in ethyl acetate (2 ml). The extracts were evaporated to dryness and analyzed by LC-MS / MS (Hewlett Packard HP1100 binary pump, Hypersil HS100 C18, by means of a 5 μt? 5 cm column with an internal diameter of 4.6 mm, using a mobile phase of 2 mM ammonium acetate in methanol / water 90:10, the aqueous portion was adjusted to pH 4 with glacial acetic acid and a flow rate of 1 ml / mirx). The mass spectrometer was a Sciex API 2000 with a TurbolonSpray interface using a positive ion multiple reaction control (MRM) detection mode. Nitrogen was used as atmosphere, nebulizer, TurbolonSpray and collision gases and the TurbolonSpray temperature was 100 ° C. The typical voltages were the following: IS = 5.2 kV; RNG = 380 V, Q0 = -10 V; 1Q1 = -11 V; ST = -15V; ROI = -11 V; MU = increase adjusted according to the Sciex user manual. The collision energy was 55 eV for high MRM, OR = 65 V. The drying time was 200 milliseconds with a pause of 50 milliseconds. "Data was acquired using MSExpress v 1.1 and processed using Macquan 1.5 (PE Sciex )) The disappearance velocity constants (k) in human microsomal preparations were determined by linear regression of the logarithmic ratio (compound under study / internal standard) versus time.The half-lives in human microsomes in vitro were determined according to with the equation tm = ln 2 / k The results of these studies demonstrate that the compounds of the present invention show desirable half-lives in human liver microsomes (HLM). Those skilled in the art will recognize that an increase in half-life in HLM is predictive of a reduction in elimination in humans of compounds predominantly eliminated by a metabolism mediated by cytochrome P450. The compounds of the invention, such as, for example, the compound of Example 1, are that they possess desirable in vitro microsomal semi-residues. Particularly preferred compounds in this invention exhibit increases of 2 times, preferably 4 times and more preferably 5 times with respect to the compound of the art. Such increases in microsomal half-lives in vitro are indicative of a reduction in elimination in vivo. The preferred compounds of formula (I) of this invention have IC50 values less than about 10 nM for the PDE5 enzyme. A more preferred group of compounds has IC5Q values less than about 5 nM for the PDE5 enzyme. Compounds having IC50 values less than about 3 nM for the PDE5 enzyme are highly preferred in this invention. In addition, the preferred compounds of formula (I) of this invention have a selectivity greater than 5 times for the enzyme PDE5 than for the enzyme PDE6. In this invention, compounds having a selectivity greater than 10 times by the PDE5 enzyme are preferred than by the PDE6 enzyme. More preferred in this invention are compounds that have a selectivity greater than 20 times for the PDE5 enzyme than for the PDE6 enzyme and compounds which have a selectivity greater than 30 times for the PDE5 enzyme are preferable to the PDE6 enzyme. Particularly preferred in this invention are compounds having an IC50 value of less than about 10 nM, more preferably less than about 5 nM and especially less than about 3nM for the PDE5 enzyme, in combination with a selectivity greater than 10 times, preferably about greater than 20 times and especially greater than 30 times by the enzyme PDE5 than by the enzyme PDE6. As detailed hereinabove, preferred compounds of this invention have desirable half-lives in human liver microsomes (HL). Especially preferred in this invention are compounds having half-lives in HLM greater than about 20 minutes, more preferably greater than 60 minutes and more preferably; greater than 120 minutes. Such HLM values can be measured in accordance with the procedures detailed earlier in this document. Thus, an especially preferred group of compounds of this invention has an IC50 value of less than about 10 mM, more preferably less than about 5 nM and especially less than about 3 nM for the PDE5 enzyme, in combination with a higher selectivity of 10 times, preferably approximately greater than 20 times and especially greater than 30 times by the enzyme PDE5 than by the enzyme PDE6 and half-lives in HLM greater than about 20 minutes. Functional Activity This can be tested in vitro by determining the ability of a compound of the invention to enhance the relaxation induced by sodium nitroprusside from tissue strips of rabbit cavernosum bodies previously contracted, as described by S.A. Ballard et al. (Brit. J. Pharmacol .., 1996, 118 (suppl.), Abstract 153P). In Vivo Activity The in vivo activity can be assayed by investigating test compounds in anesthetized dogs to determine their capacity, after administration i. v, to enhance the pressure increases in the corpora cavernosa of the penis induced by the intracavernous injection of sodium nitroprusside, using a procedure based on that described by Trigo-Rocha et al. . { Neurourol. and Urodyn. , 1994, 13, 71). Safety Profile Compounds can be tested at variable doses i.v. and p.o. in animals such as the mouse and the dog, observing any unwanted effects. EXAMPLES AND PREPARATIONS The synthesis of the compounds of general formula (I) and of the intermediates for use in this document can be performed by analogy with the procedures of the Examples and Preparations shown below. Nuclear magnetic resonance (NMR) spectra of ¾ were recorded using a Varian Unity 300 spectrometer or a Varian Inova 400 spectrometer, and in all cases were consistent with the proposed structures. The characteristic chemical shifts (d) are given in parts per million downfield of tetramethylsilane using conventional abbreviations for the denomination of the main peaks: for example, s, singlet; d, doublet; t, triplet; q, quadruple; m, multiplet; a, wide. Mass spectra (m / z) were recorded using a Fisons Instruments Trio mass spectrometer in thermospray ionisation mode (TSP) or using a Finnigan Navigator in electrospray ionisation (ES) mode - positive ionization mode and / or negative. As used herein, the term "column chromatography" refers to a normal phase chromatography using silica gel (0.04-0.06 rare), Ambient temperature includes 20 to 25 ° C. EXAMPLES Preparation Preparation 1 N-propionylalanine Trimethylsilyl chloride (52.4 ml, 0.41 mol) was added dropwise to an ice-cooled solution of D, L-alanine (16.71 g, 0.188 mol) and trxethylamine ( 57.5 ml, 0.41 mol) in dichloromethane (190 ml). After the addition was complete, the solution was stirred at room temperature for 1 hour, followed by 1 hour at 40 ° C. Then, the solution was cooled to -10 ° C, propionyl chloride (16.29 ml, 0.188 mol) was added dropwise over 15 minutes and, upon completion of the addition, the reaction was stirred at -10 ° C for 2 hours and then for 16 hours at room temperature, before cooling in an ice bath. Water (100 ml) was added, the mixture was stirred for 15 minutes and then the phases were separated. The aqueous layer was evaporated under reduced pressure and the residue was triturated with acetone. The resulting solid was removed by filtration and the filtrate was concentrated under reduced pressure to give an oil. This oil was purified by column chromatography using DCM: MeOH: NH3 (aq) 0.88 (89: 10: 1) as eluent to give the title compound (20 g, containing 33% triethylamine). X H RM (DMSO d6 300 MHz): d = 0.98 (t, 3H), 1.20 (d, 3H), 2.07 (q, 2H), 4.08 (m, 1H), 7.80 (d, 1H), 8.57-9.00 (sa, 1H). Preparation 2 N-Methoxy-N-methyl-2- (propionylamino) propanamide 1- (3-Dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (16.2 g, 84.7 mmol) was added to a suspension of the title compound of Preparation 1 (14.85 g, 77.0 mmol) triethylamine (27.9 ml, 72.5 mmol), N, 0-dimethylhydroxylamine hydrochloride (7.5 g, 77 mmol) and l-hydroxybenzotriazole hydrate (12 , 3 g, 80.85 mmol) in dichloromethane (450 ml) and the reaction was stirred at room temperature for 23 hours. The mixture was washed with water (250 ml) and sodium bicarbonate solution (120 ml), dried (MgSO 4), filtered and evaporated under reduced pressure. The residual oil was purified by column chromatography using DCM: MeOH (95: 5) as eluent, yielding the title compound (8.2 g). NMR (CDC13, 300 MHz): d = 1.17 (t, 3H), 1.34 (d, 3H), 2.22 (q, 2H), 3.20 (s, 3H), 3.79 (s, 3H), 4.98 (m, 1H), 6.23 (sa, 1H). Preparation 3 N- (3-Ethoxy-1-methyl-2-oxo-3-butenyl) propanamide Tert-butyl-lithium (70 ml, 1.7 M in pentane, 119 mmol) was added over 5 minutes to a cooled solution. (-78 ° C) ethyl vinyl ether (11.4 ml, 119 mmol) in tetrahydrofuran (160 ml) and the solution was allowed to warm to -5 ° C for 1 hour. The solution was then cooled again to -60 ° C and magnesium bromide diethyletherate (30.73 g, 119 mmol) was added in portions so that it was maintained at an internal temperature less than -50 ° C. Then, the mixture was allowed to warm to -5 ° C, stirred for 30 minutes and cooled again to -10 ° C. A solution of the title compound of Preparation 2 (2.8 g, 14.9 mmol) in THF (20 mL) was added dropwise and the reaction was then stirred at room temperature for 3 hours. The mixture was poured into a 10% aqueous solution of citric acid (500 ml) and extracted with EtOAc (500 ml). The organic solution was dried (MgSO 4), filtered and evaporated under reduced pressure to give an oil. The crude product was purified by column chromatography using DCM as eluent, yielding the title compound (1.8 g). lH NMR (CDC13, 300 MHz): S = 1.18 (t, 3H), 1.38 (m, 6H), 2.23 (q, 2H), 3.83 (q, 2H), 4.54 (d, 1H), 5.24 (m, 2H), 6.35 (m, 1H). Preparation 4 Ethyl 2-OXO-3- (propionylamino) butanoate Procedure A Oxygen was bubbled through a cooled (-78 ° C) solution of the title compound of Preparation 3 (1, 0 g, 5.98 mmol) and pyridine (3.25 mL, 44.9 mmol) in DCM (85 mL) for 2 minutes. Then, ozone was bubbled through it for 5 minutes and the solution was then purged with oxygen and placed under a nitrogen atmosphere. Dimethyl sulfide (3.25 ral, 44.9 mmol) was added dropwise over 5 minutes, the solution was stirred for 1 hour and then allowed to warm to room temperature. The mixture was washed with water, dried (Na2SO4), filtered and evaporated under reduced pressure to give an oil. The crude product was purified by column chromatography using an elution gradient of DCM: Et20 (100: 0 to 50:50), yielding the title compound (335 mg). Method B 4-Diraethylaminopyridine (122 mg, 1.0 mmol) was added to a solution of the title compound of Preparation 1 (10.9 g, 75.0 mmol) in pyridine (18.2 mL, 225 mmol) and THF (75 mi). The solution was refluxed and then ethyl oxalyl chloride (16.8 ml, 150 mmol) was added dropwise over 1 hour. During the first half of the addition, the reaction mixture remained as a solution, however, as more ethyloxyalyl chloride was added a white precipitate formed which did not re-dissolve. The mixture was heated for a further 3 hours and then poured into ice-cold water (200 ml). The mixture was extracted with EtOAc (3 x 200 mL) and the combined organic extracts were dried (MgSO 4), filtered and concentrated in vacuo to yield a pale brown oil. NaHCO3 (3.58 g, 42.7 mmol) and EtOH (25 mL) were added and the mixture was heated to reflux for 3.5 hours. The reaction was cooled and filtered. The filtrate was concentrated to a pale brown oil. The crude product was purified by column chromatography (pentane / EtOAc, 80:20 to 20:80), yielding the title compound as a yellow oil (3.95 g, 20.0 mmol, 26%). * H NMR (CDC13, 300 MHz): 5 = 1.18 (t, 3H), 1.38 (m, 6H), 2.23 (g, 2H), 4.38 (q, 2H), 5, 18 (m, 1H), 6.02 (m, 1H). Preparation 5 2-Butoxynicotinic acid 2-Chloronicotinic acid (10.0 g, 63.5 mmol) was added to a solution of sodium (3 g, 130 mmol) in butanol (100 mL) at 80 ° C and the resulting mixture was heated to 20 ° C. reflux for 4 hours. The reaction was allowed to cool and partitioned between EtOAc and 2 M HC1 (giving a pH of 3-4) and the layers were separated. The organic phase was washed with brine, concentrated under reduced pressure, redissolved in EtOAc, dried (MgSO 4), filtered and evaporated under reduced pressure to give the desired product as a solid (11.9 g). ). 1K NMR (ÓVDMSO, 400 MHz): d = 0.90 (t, 3H), 1.40 (, 2H), 1.65 (ra, 2H), 4.30 (t, 2H), 7.00 ( m, 1H), 8.05 (d, 2H), 8.30 (d, 1H) LCMS: m / z 196.3 (MH +) Preparation 6 2-Butoxy-5-iodonicotinic acid A mixture of the title compound of Preparation 5 (3.46 g, 17.7 mmol) and N-iodosuccinimide (6 g, 26.6 mmol) in trifluoroacetic acid: trifluoroacetic anhydride (4: 1, 35 ml) was refluxed for 24 hours, protected from light. The cooled reaction mixture was concentrated under reduced pressure and the residue was dissolved in EtOAc. This solution was then washed sequentially with water (twice), a sodium thiosulfate solution (twice), a 10% aqueous solution of sodium citrate, 2 N hydrochloric acid and brine, then dried (MgSO4), filtered and evaporated under reduced pressure. The crude product was triturated with pentane, yielding the title compound as a white solid (3.86 g, 68%). ¾ NMR (CDC13, 300 MHz): 5 = 1.00 (t, 3H), 1.50 (ra, 2H), 1.85 (m, '2H), 4.60 (t, 2H), 8, 50 (s, 1H), 8.70 (s, 1H), 10.50 (sa, 1H). CLE: m / z 322 (MH +) Preparation 7 2-Butoxy-5-iodonotinone ryl

[0159],, - -dimethylformamide (3 drops) was added to an ice-cooled suspension of the title compound of Preparation 6 (2.25 g, 7.01 mmol), and oxalyl chloride (3.55 g, 28.0 mmol) in DCM (20 mL) and the reaction was stirred at room temperature for 4 hours. The mixture was concentrated under reduced pressure and the residue was azeotropically distilled with DCM. The acid chloride was resuspended in DCM (20 mL), cooled in an ice bath, 0.88 ammonia (2 mL) was added and the solution was stirred at room temperature for 30 minutes. The reaction mixture was diluted with DCM, washed with water, 2 M HCl and brine, then dried (MgS < ¾), filtered and evaporated under reduced pressure to give a brown solid. A solution of trifluoroacetic anhydride (1.82 g, 8.67 mmol) in dioxane (2 mL) was added to an ice-cooled solution of the intermediate amide (1.85 g, 5.78 mmol) and pyridine (1, 14 g, 14.4 mmol) in dioxane (15 mL), and the reaction was stirred at room temperature for 3 hours. The mixture was concentrated under reduced pressure and the residue was partitioned between EtOAc and water and the laywere separated. The organic layer was washed with 2 M HCl (twice), a saturated solution of sodium bicarbonate and brine, then dried (MgSO 4), filtered and evaporated under reduced pressure. The crude product was purified by column chromatography using an elution gradient of pentane: EtOAc (100: 0 to 95: 5) to give the title compound. NMR (CDC13, 300 Hz): d = 0.98 (t, 3H), 1.50 (m, 2H), 1.80 (m, 2H), 4.40 (t, 2H), 8.08 (s, 1H), 8.50 (s, 1H). LCMS: m / z 303.0 (MH +) Preparation '8 2-Butoxy-5-iodo-3-pyridinocarboximidamide formate The title compound of Preparation 7 (10 g, 33.1 mmol) was added to a prepared solution recently sodium (1.5 g, 65.2 mmol) in butanol (100 mL) and the reaction was stirred at room temperature for 18 hours. Ammonium formate was added (17.4 g, 276 mmol) and the reaction was heated at 50 ° C for 2 hours, followed by a further 2 hours at 80 ° C. The cooled mixture was concentrated under reduced pressure and the residue was triturated with Et20. This solid was triturated with water and then triturated several times with ether, yielding the title compound (2.53 g), which was used without further purification.

X H NMR (d 6 -DMSO, 400 MHz): d = 0.90 (t, 3H), 1.39 (t ?, 2H), 1, S9 (m, 2H), 4.30 (t, 2H), 8.28 (s, 1H), 8.42 (s, 1H), 8.59 (s, 1H). Preparation 9 2- (2-Butoxy-5-iodo-3-pyridinyl) -7-ethyl-5-methylimidazo G5.1- f] [1,2,4] triazin-4 (3H) -one Procedure A Added hydrazine monohydrate (194 μl, 3.98 mmol) to a solution of the title compound of Preparation 8 (2.02 g, 3.98 mmol) in ethanol (3.8 ml) and the solution was stirred for 20 minutes. minutes A solution of the title compound of Preparation 4 (800 mg, 3.98 mmol) in ethanol (1 mL) was added and the reaction was heated at 70 ° C for 2 hours. The cooled mixture was concentrated under reduced pressure and the residue was purified by column chromatography using DCM: Et20 (67:33) as eluent, giving a yellow solid. This was triturated with ether, yielding a yellow solid, 250 mg, (a 2: 1 isomeric mixture of the desired and unwanted product). Phosphorus oxychloride (360 μ ?, 3.97 mmol) was added to a solution of this solid (243 mg, 0.516 mmol) in 1,2-dichloroethane (3 mL) and the reaction was refluxed for 30 minutes. The cooled mixture was evaporated under reduced pressure and the residue was partitioned between a solution of 2 M sodium carbonate (5 ml) and EtOAc (5 ml) and the layers were separated. The aqueous layer was extracted with EtOAc (2 x 5 mL) and the combined organic solutions were dried (MgSO 4), filtered and evaporated under reduced pressure to give a yellow solid. The crude product was purified by column chromatography using DCM: Et20 (91: 9) as eluent, yielding the title compound (130 mg). Method B Hydrazine monohydrate (91 μL, 1.87 mmol) was added to a suspension of the title compound of Preparation 16 (834 mg, 1.87 mmol) in BuOH (8 mL) and the mixture was stirred at room temperature during 15 minutes. The title compound of Preparation 4 (prepared by procedure B, 376 mg, 1.87 mmol) and NaHCO 3 (525 mg, 6.25 mmol) were added and the mixture was heated to reflux for 6 hours. Then, the mixture was stirred at room temperature for 18 hours and partitioned between water (100 ml) and DCM (2 x 150 ml). The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo to yield a brown oil. This was dissolved in DCM (15 mL) and POC13 (1.03 mL, 11.1 mmol) was added. The solution was heated to reflux for 1 hour and then cooled to room temperature. A saturated solution of NaHCO 3 (100 mL) was added and the mixture was stirred for 1 hour. The mixture was extracted with DCM (2 x 75 mL) and the combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo to yield a brown solid. The crude product was purified by column chromatography (Pentane / EtOAc, 60:40), yielding the title compound as a beige solid (200 mg, 0.44 mmol, 24%). LM NMR (CDC13, 400 MHz): d = 1.01 (t, 3H), 1.41 (t, 3H), 1.58 (sextete, 2H), 1.88 (quintete, 2H), 2.63 (s, 3H), 3.05 (q, 2H), 4.56 (t, 2H), 8.50 (s, 1H), 8.76 (s, 1H), 9.80 (sa, 1H) .

LCMS (ES +): m / z 454 (MH +). Combustion analysis: Calculated for C17H20IN5O2: C, 45.05; H, 4.45; N, 15.45. Found: C, 44.79; H, 4.27; N, 15.18. Preparation 10 5- (2-Butoxy-5-trimethylsilylethynyl-3-pyridinyl) -2- G2- (dimethylamino) -etill -3-ethyl-2,6-dihydro-7-pyridyl-G, 3- d] -irimidin-7 -one Pd (PPh3) 2Cl2 (11.2 mg, 0.016 mraol), trimethylsilylacetylene (179 μ ?, 1.29 mmol) and cuprous iodide (3 mg, 0.016 mmol) were added to a stirred suspension of 5- (2- butoxy-5-iodo-3-pyridinyl) -2- [2- (dimethylamino) -ethyl] -3-ethyl-2,6-dihydro-7-yl-pyrazolo [4, 3-d] -piximidin-7-one ( Example 44 in Annex 1, PCT application, IB 00/01430) (330 mg, 0.647 mmol) in triethylamine (8 ml) and acetonitrile (2 ml) at room temperature under a nitrogen atmosphere. The mixture was heated at 60 ° C for 3 h, cooled and extracted in brine with dichloromethane (2 x 100 mL). The organic extracts were dried (MgSO 4), filtered and concentrated to give a yellow solid. Purification by flash column chromatography (elution with DCM / MeOH, 95: 5) gave the title compound as a pale brown oil (290 mg, 93%). ¾ R (300 MHz, CDC13): ü = 0.30 (s, 9H), 1.00 (t, 3H), 1.40 (t, 3H), 1.50 (m, 2H), 1.90 (m, 2H), 2.30 (s, 6H), 2.90 (t, 2H), 3.05 (q, 2H), 4.40 (t, 2H), 4.60 (t, 2H) , 8.30 (s, 1H), 8.80 (s, 1H), 10.70 (s, 1H).

LCMS (TSP): m / z 481.3 (MH +). Preparation 11 5- (2-Butoxy-5-ethynyl-3-pyridinyl) -2- G2- (dimethylamino) ethyl -3-ethyl-2,6-dihydro-7.ff-pyrazolo G4, 3-d] pyrimidine- 7-one Potassium fluoride (72.5 mg, 1.25 mmol) was added to a stirred solution of the title compound of Preparation 10 (300 mg, 0.625 mmol) in 2 T, iV-dimethylformamide (10 mL) and water (2 ml) at room temperature. After 2 hours, the reaction mixture was poured into brine and extracted with EtOAc (2 x 100 mL). The organic extracts were dried (MgSO 4), filtered and concentrated to give the product (285 mg) as a pale brown oil. ¾ NMR (300 MHz, CDC13): 5 = 1.00 (t, X3H), 1.40 (t, 3H), 1.50 (m, 2H), 1.90 (m, 2H), 2.30 (s, 6H), 2.90 (t, 2H), 3.00 (q, 2H), 4.40 (t, 2H), 4.60 (t, 2H), 8.40 (s, 1H) 8.80 (s, 1H), 10.70 (s, 1H).

LCMS (ES +): m / z 409 (MH +). Preparation 12 5- (5-Acetyl-2-butoxy-3-pyridinyl) -2- G2- (dimethylamino) -3-ethyl-2,6-dihydro-7H-pyrazolo G4, 3 -di-irimidin-7-one 1 N Sulfuric acid (1 mL) was added to a stirred solution of the title compound of Preparation 11 (280 mg, 0.69 mmol) in acetone (8 mL) at room temperature. Mercury sulfate (40 mg, 0.14 mmol) was added and the mixture was heated to reflux for 5 hours. The reaction mixture was cooled, diluted with methanol (10 mL), filtered and the filtrate was washed with more methanol.

The solvent was evaporated and the residue was partitioned between EtOAc (100 mL) and a saturated solution of sodium bicarbonate (100 mL). The aqueous extract was washed with 100 ml more EtOAc and the combined organic extracts were dried (g S04), filtered and concentrated. Purification by flash column chromatography (elution with DC / MeOH, 95: 5) gave the product as a cream colored solid (140 mg). ! H RM (300 MHz, CDC13): d = 1.00 (t, 3H), 1.40 (t, 3H), 1.50 (m, 2H), 1.90 (m, 2H), 2, 30 (s, 6H), 2.60 (s, 3H), 2.90 (t, 2H), 3.05 (q, 2H), 4.40 (t, 2H), 4.70 (t, 2H) ), 8.80 (s, 1H), 9.20 (s, 1H), 10, 60 (s, 1H). LCMS (TSP): m / z 427.5 (MH +). Preparation 13 2-Ethoxy-5-iodonicotinamide Oxalyl chloride (6.60 ml, 75.1 mmol) was added with a solution of 2-ethoxy-5-iodonotinic acid (prepared according to the procedure described in WO 0127112, 20.0 g, 68.3 mmol) in DCM (400 ml) and N, N-dimethylformamide (0.1 ml) at 0 ° C. The solution was warmed to room temperature for 18 hours and then concentrated in vacuo. The resulting orange oil was dissolved in THF (200 ml) and cooled to 0 ° C. NH 3 (410 ml of a 0.5 M solution in dioxane, 205 mmol) was added and the mixture was heated at room temperature for 4 hours. The reaction mixture was concentrated in vacuo and triturated with water (150 ml). The solid was filtered and dried, yielding the title compound as a beige solid (18.9 g, 64.9 mmol, 95%); p.f. 176-179 ° C.

¾ NMR (d6-DMSO, 400 MHz): d = 1.35 (t, 3H), 4.40 (q, 2H), 7.60 (sa, 1H), 7.75 (sa, 1H), 8 , 30 (s, 1H), 8.50 (s, 1H). LCMS (ES +): m / z 607 (2M a +). Preparation 14 2 -Butoxy-5-iodonicotinamide A mixture of the title compound of Preparation 13 (10.0 g, 34.0 mmol) and Cs2CO3 (5.60 g, 17.0 mmol) in BuOH (50 mL) was it was heated at reflux for 4.5 hours and then stirred at room temperature for 18 hours. The mixture was concentrated in vacuo and partitioned between water (200 ml) and DCM (2 x 250 ml). The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo. The crude product was triturated with Et20, yielding the title compound as a beige solid (4.81 g, 15.0 mmol, 44%); p.f. 163-166 ° C. ¾ NMR (CDC13, 400 MHz): d = 1.00 (t, 3H), 1.50 (sextet, 2H), 1.80 (quint, 2H), 4.50 (t, 2H), 6.00 (sa, 1H), 7.75 (ss, 1H), 8.45 (s, 1H), 8.75 (s, 1H). LCMS (ES +): m / z 343 (MNa +). Combustion analysis: Calculated for C10H13IN2O2.0, 15H20: C, 37.21; H, 4.15; N, 8.68. Found: C, 36.97; H, -3.92; N, 8.62. Preparation 15 2 -Butoxy -5-iodo-3-pyridinocarbothioamide A mixture of the title compound of Preparation 14 (4.81 g, 15.0 mmol) and Lawesson's reagent (3.04 g, 7.50 mmol) in toluene (40 ml) was heated at 90 ° C for 2 hours and then stirred at room temperature for an additional 18 hours. The reaction mixture was concentrated to half its volume and cooled to 0 ° C. The yellow precipitate was filtered and dried to yield the title compound (3.68 g, 10.9 mmol, 73%); p.f. 140-148 ° C. ¾ NMR (CDC13, 400 MHz): d = 1.00 (t, 3H), 1.45 (sextet, 2H), 1.80 (quint, 2H), 4.50 (t, 2H), 8.00 (br s, 1H), 8.45 (s, 1H), 9.20 (br s, 1H), 9.25 (s, 1H). LCMS (ES-): m / z 335 (M-H) +. Preparation 16 Methyl 2-butoxy-5-iodo-3-pyridinocarbimidothioate hydroiodide The title compound of Preparation 15 (3.68 g, 10.9 mmol) and iodomethane (1.5 ml, 24 mmol) were dissolved in DCM (20 mL) and acetone (30 mL) and stirred at room temperature for 3 days. The reaction mixture was concentrated in vacuo and triturated with Et20, yielding the title compound as a brown solid (4.08 g, 8.53 mmol, 78%). ¾ RM (d6-DMSO, 400 MHz): d = 0.90 (t, 3H), 1.40 (sextet, 2H), 1.70 (quint, 2H), 2.70 (s, 3H), 4 , 30 (t, 2H), 8.30 (s, 1H), 8, 60 (s, 1H). LCMS (ES +): m / z 351 (MH +). Preparation 17 2- (Propionylamino) -4-pentenoic acid Propionic anhydride (18.0 ml, 140 mmol) was added dropwise to a solution of DL-2-amino-4-pentenoic acid (14.6 g, 127 mmol ) and K2CO3 (19.3 g, 140 mmol) in H20 (100 mL) at 0 ° C. The reaction mixture was heated to 20 ° C and stirred for 18 hours. Concentrated HCl was added until the pH was 1 and the mixture was extracted with DCM (2 x 100 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo. The crude product was triturated with pentane (100 ml), yielding the title compound as white crystals (18.9 g, 110 mmol, 87%); p.f. 96-98 ° C. ¾ KMN (400 MHz, CDCl 3): ü = 6.25 (d, 1H), 5.70 (m, 1H), 5.15 (df 2H), 4.70 (q, 1H), 2, 65 (m, 1H), 2.55 (m, 1H), 2.30 (q, 2H), 1.15 (t, 3H). LCMS (ES +): m / z 172 (MH +). ^ 'Combustion analysis: calculated for C8H13N03: C, 56.13; H, 7.65; N, 8.18. Found C, 56.04; H, 7.56; N, 8.11. Preparation 18 JV-methoxy-i7'-methyl-2- (propionylamino) -4-pentenamide 2-Chloro-4,6-dimethoxy-1,3,5-triazine (14.47 g, 82.0 mmol) was added to a solution of the title compound of Preparation 17 (12.74 g, 75.0 mmol) in THF (100 mL) and N-methylmorpholine (18.2 mL, 165 mmol) at 20 ° C. After 1 hour, a white precipitate formed. N, O-dimethylhydroxylamine hydrochloride (7.80 g, 80.0 mmol) was added and the mixture was stirred at 20 ° C for 3 days. The reaction mixture was concentrated in vacuo and partitioned between DCM (150 ml) and H20 (50 ml). The aqueous phase was extracted from DCM (50 ml) and the combined organic extracts were washed with a solution of 10% Na 2 SO 3 and HC 1 2 (50 ml). The DCM solution was dried (Na2S04), it was filtered and concentrated in vacuo. The crude product was purified by column chromatography (ethyl acetate), yielding the title compound as a yellow oil (12.3 g, 57.4 mmol, 77%). ¾ NMR (400 MHz, CDCl 3): υ = 6.10 (sa, 1H), 5.70 (m, 1H), 5.10 (m, 3H), 3.80 (s, 3H), 3.20 (s, 3H), 2.55 (m, 1H), 2.40 (m, 1H), 2.20 (g, 2H), 1.15 (t, 3H). LCMS (ES +): m / z 237 (MNa +). High resolution MS: m / z calculated for C10H18N2O3Na: 237.1210; found: 237.1213 (MNa +). Preparation 19 N- (1-Formyl-3-butenyl) propanamide LiAlH 4 (1 M in THF, 34.0 mL, 34.0 mmol) was added dropwise over 45 minutes to a solution of the title compound of Preparation 18 (10.5 g, 49.0 mmol) in THF in an N2 atmosphere at -10 ° C. The reaction was heated to 20 ° C and stirred for 3 hours. A solution of KHS04 (20 g in 150 mL H20) was carefully added and the mixture was stirred for 10 minutes and then concentrated in vacuo to remove the THF. The aqueous phase was extracted with DCM (2 x 100 mL) and the organic extracts were dried (Na 2 SO 4), filtered and concentrated in vacuo. The crude product was chromatographed by column (1: 1, pentane / EtOAc), yielding the title compound as a yellow oil (3.30 g, 21.3 mmol, 43%).

J H NMR (400 MHz, CDCl 3): d = 9.60 (s, 1 H), 6.00 (s, 1 H), 5.70 (m, 1 H), 5.10 (m, 2 H), 4.60 (q, 1H), 2.60 (m, 2H), 2.20 (q, 2H), 1.15 (t, 3H). Preparation 20 N- (1-fCyano (hydroxy) methyl-3-butenyl} propanamide Cyanhydrin-acetone (2.0 ml, 22 mmol) was added to a solution of the title compound of Preparation 19 (3.30 g, 21.3 mmol) in DCM (50 ml) and Et3N (3.1 ml) and the mixture was stirred for 18 hours at 20 ° C. An additional 0.5 ml of cyanohydrin-acetone was added and the mixture was stirred for 18 hours. The reaction was concentrated in vacuo and the crude product was purified by column chromatography (pentane / EtOAc, 60: 40-40: 60), yielding the title compound 'as a 1: 1 mixture of diastereoisomers, yellow oil (2.35 g, 12.9 mmol, 61%). ¾ NMR (400 MHz, CDCl 3): d = 5.90 (m, 1 H), 5.75 (m, 1 H), 5.20 ( m, 2H), 4.70 (m, 0.5H), 4.55 (m, 0.5H), 4.20 (m, 0.5H), 4.00 (m, 0.5H), 2 20-2.50 (m, 4H), 1.20 (m, 3H), LCMS (ES +): m / z 205 (M a +), high resolution MS: m / z calculated for CgHi5N202: 183, 1128 , Found: 183.1134 (MH +). Preparation 21 2-Hydroxy-3- (propionylamino) -5-h Ethyl Exoate HCl was bubbled through a solution of the title compound in Preparation 20 (2.35 g, 12.9 mmol) in EtOH (40 mL) at -10 ° C until saturated. The reaction was heated to 5 ° C and the container was sealed and kept in a refrigerator at 5 ° C for 18 hours. The reaction mixture was concentrated in vacuo, ice (~ 100 g) was added and the mixture was heated to 20 ° C and stirred for 30 minutes. The aqueous phase was basified with a 10% Na 2 CO 3 solution and DCM (100 mL) was extracted. 2M HC1 (50 ml) was added to the DCM extract and the mixture was stirred for 30 minutes. The DCM layer was separated, washed with a 10% Na 2 CO 3 solution (100 ml), dried (NaSO 4), filtered and concentrated in vacuo to an oil. All the aqueous phases were combined (H ~ 6) and extracted with DCM (4 x 40 mL). The combined extracts were dried (Na 2 SO 4), filtered and concentrated in vacuo to an oil. This was combined with the previous oil, yielding the title compound (2.00 g, 8.7 mmol, 67%). x XH RM (400 MHz, CDC13): 5 = 5.60-5, 80 (m, 2H), 5.10 (m, 2H), 4.40 (m, 1H), 4.20 (m, 3H ), 3.40 (ss, 0, 5H), 3.20 (ss, 0.5H), 2.40 (q, 1H), 2.20 (m, 3H), 1.30 (m, 3H) , 1.10 (m, 3H). LCMS (ES-): m / z 228 (M-H +). High resolution MS: m / z calculated for CnH20NO4: 230.1387; Found.- 230.1395 (MH +). Preparation 22 Dess-Martin periodinane (4.25 g, 10 mmol) was added to a solution of the title compound of Preparation 21 (2.00 g, 8.73 mmol) in DCM (40 ml) at 20 ° C. After 1.5 hours a saturated solution of Na2S203 (50 ml) and a saturated solution of NaHCO3 (50 ml) were added and the mixture was stirred for 30 minutes. The layers were separated and the aqueous phase was extracted with DCM (2 x 50 mL). The combined organic extracts were dried (Na 2 SO 4) filtered and concentrated in vacuo. The crude product was purified by column chromatography (pentane / EtOAc, 75: 25-25: 75), yielding the title compound as a pale yellow oil (1.30 g, 5.72 mmol, 65%). ¾ R (400 MHz, CDC13): d = 6.00 (sa, 1H), 5.65 (tdd, 1H), 5.25 (q, 1H), 5.15 (dd, 1H), 5.10 (dd, 1H), 4.35 (q, 2H), 2.70 (dt, 1H), 2.50 (ddd, 1H), 2.25 (q, 2H), 1.35 (t, 3H) , 1.15 (t, 3H). CLE (ES +): m / z 228 (MH +), 250 (MNa +). High resolution MS: m / z calculated for CuH17N04Na: 250.1050; found: 250.1057 (MNa +). Preparation 23 5-A1I1-2- (2-Butoxy-5-iodo-3-pyridinyl) -7-ethylimidazo G5, 1- f1 n, 2, 41 triazin-4 OH) -one Hydrazine monohydrate (0.11) was added mi, 2.25 mmol) was added to a suspension of the title compound in Preparation 16 (1.00 g, 2.10 mmol) in BuOH (10 mL) and the mixture was stirred at room temperature for 15 minutes. The title compound of Preparation 22 (470 mg, 2.07 mmol) and NaHCO3 (600 mg, 7.06 mmol) were added and the mixture was heated to reflux for 6 hours and then cooled to room temperature for 18 hours . The mixture was partitioned between DCM (3 x 100 mL) and a saturated solution of NaHCO3 (50 mL) and the combined organic extracts were dried (Na2SO4)., they were filtered and concentrated in vacuo. The resulting brown oil was dissolved in 1,2-dichloroethane (10 mL) and POCl3 (1.6 mL, 17.1 mmol) was added to this solution. This solution was refluxed for 30 minutes and then cooled. Aqueous 10% Na 2 CO 3 (20 mL) was added and the mixture was stirred for 15 minutes. This mixture was partitioned between DCM (3 x 50 mL) and 10% aqueous Na2CO3 (50 mL) and the combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo.The resulting brown gum was purified by chromatography column (DCM / EtOAc, 80:20) and triturated with diisopropyl ether, yielding the title compound as a beige solid (185 mg, 0.38 mmol, 18%); p.f. 134-135 ° C. ¾ NMR (400 Hz, CDCl 3): 5 = 9.90 (sa, 1H), 8.75 (s, 1H), 8.50 (s, 1H), 6.10 (ddt, 1H), 5.20 (dd, 1H), 5.10 (dd, '1H), 4.50 (t, 2H), 3.80 (d, 2H), 3.05 (q, 2H), x 1.90 (pentete, 2H), 1.55 (sextete, 2H), 1.40 (t, 3H), 1 , 00 (t, 3H). LCMS (ES +): m / z 480 (MH +). Combustion analysis: Calculated for C19H22IN502: C, 47.61; H, 4.63; N, 14.51. Found: C, 47.32; H, 4.56; N, 14.30 Preparation 24 2- (2-Butoxy-5-vodo-3 ~ pyridinyl) -7-ethyl-5-propylimidazo G5, 1- fl ("1,2,41 triazin-4 (3H) -one The title compound of Preparation 23 (75 mg, 0.156 mmol), tosyl hydrazide (120 mg, 0.645 mmol) and toluene (2 mL) were combined and refluxed for 5 hours.The mixture was stirred at room temperature for 18 hours and then partitioned between water (15 ml) and EtOAc (30 ml) The organic phase was washed with brine (10 ml) and a 0.2 M NaOH solution (2 x 10 ml), dried ( Na2SO4), filtered and concentrated to yield the title compound as a white solid (70 mg, 0.146 mmol, 93%). ¾ NMR (400 MHz, CDC13): d = 9.85 (br, 1H), 8.75 (s, 1H), 8.50 (s, 1H), 4.55 (t, 2H), 3.05 (q, 2H), 3.00 (t, 2H), 1, 90 (pentete, 2H), 1.80 (sextet, 2H), 1.55 (m, 2H), 1.40 (t, 3H), 1.00 (2 overlapping triplets, 6H), CLEM (ES +) - m / z 482 (MH +). Preparation 25 2- (2-Butoxy-5-iodo-3-pyridinyl) -7-ethyl-4-oxo-3, 4- dihi droimidazo [5, l-jl f1, 2, 41 triazine-5-carbaldehyde NaI04 (120 mg, 0.56 mmol), and Os04 (2.5% solution in t-BuOH, 0.09 ml) were added to a solution of the title compound of Preparation 23 (90 mg, 0.188 mmol) in THF (6 mL) and water (3 mL) and the mixture was stirred at room temperature for 18 hours. The mixture was partitioned between EtOAc (50 mL) and water (30 mL) and the organic phase was dried (I \2SO4), filtered and concentrated in vacuo. The crude product was purified by column chromatography (pentane / EtOAc, 60:40 to 40:60), yielding the title compound as a pale yellow solid. 1K NMR (400 MHz, CDC13): d = 10.55 (br s, 1H), 10.45 (s, 1H), 8.80 (s, 1H), 8.60 (s, 1H), 4.60 (t, 2H), 3.20 (q, 2H), 1.90 (pentete, 2H), 1.55 (m, 2H), 1.50 (t, 3H), 1.05 (t, 3H) . LCMS, (ES-): m / z 466 (M-H +). High resolution MS: m / z calculated for C17H18N5I03: 468.0527; found: 468.0518 (?? +). Preparation 26 2- (2-Butoxy-5-vodo-3-pyridinyl) -7-ethyl-5- Í4- | morpholinylmethyl) imidazo [5,1-fl [1, 2, 41 triazin-4- (3H) - The title compound of Preparation 25 was combined (50 mg, 0.107 mmol), morpholine (0.015 mL, 0.172 mmol), AcOH (0.010 mL, 0.175 mmol) and NaBH (OAc) 3 (50 mg, 0.236 mmol) in THF (2 mL) and stirred at room temperature for 3 days. The mixture was partitioned between DCM (30 ral) and a saturated solution of NaHCO3 (20 mL). The organic phase was dried (Na2SO4), filtered and concentrated in vacuo to afford the title compound as a beige solid (38 mg, 0.071 mmol, 68%). ¾ NMR (400 MHz, CDCl 3): d = 8.75 (S, ¾1H), 8.50 (s, 1H), 4.50 (t, 2H), 4.00 (s, 2H), 3.75 (m, 4H), 3.10 (q, 2H), 2.65 (ra, 4H), 1.85 (pentete, 2H), 1.50 (m, 2H), 1.40 (t, 3H) , 1.00 (t, 3H). LCMS (ES +): m / z 539 (H +). High resolution MS: m / z calculated for C21H2-7N6I03: 539.1262; found: 539.1260 (MH +). E emolo 1 2- (5-Acetyl-2-butoxy-3-pyridinyl) -7-ethyl-5-methylimidazo I5, 1- f] G? , 2, 41 triazin-4 (3H) -one Butyl vinyl ether (1.30 ml, 10.0 mmol) and triethylamine (0.20 ml, 1.43 mmol) were added to a solution of the title compound of Preparation 9 (prepared by procedure-B, 200 mg , 0.44 mmol) in MeCN (5 mL). Pd (OAc) 2 (16 mg, 0.07 mmol) and tri-o-tolylphosphine (42 mg, 0.14 mmol) were added and the mixture was heated to reflux for 1.5 hours and then stirred at room temperature for 18 hours The reaction was refluxed for a further 2 hours, cooled and concentrated in vacuo The resulting solid was suspended in 6 M HC1 (4 mL) and stirred for 1 hour at room temperature. diluted with water (20 ml) and extracted with ethyl acetate (2 x 150 ml) and DCM (2 x 50 ml) The combined organic extracts were dried (Na 2 SO 4), filtered and concentrated in vacuo, yielding an oil The crude product was purified by column chromatography (DCM / MeOH, 98: 2), yielding the title compound as a pale yellow solid (40 mg, 0.11 mmol, 25%).; p.f. 190-196 ° C. ¾ RM (400 MHz, CDCl 3): S = 1.05 (t, 3H), 1.40 (t, 3H), 1.55 (sextet, 2H), 1.90 (quintet, 2H), 2.65 (2 superimposed singles, 6H), 3.05 (q, 2H), 4.65 (t, 2H), 8.90 (s, 1H), 9.00 (s, 1H), 9.70 (sa, 1 HOUR) . LCMS (ES +): m / z 370 (MH +). Combustion analysis: Calculated for, 2H20: C, 61.18; H, 6.32; N, 18.77. Found: C, 61.25; H, 6.23; N, 18.49. Alternatively, Example 1 can be prepared from the title compound of Preparation 9 following the procedure used to prepare the title compound of Preparation 12 of Example 44 in Annex 1, PCT Application, IB 00/01430. Example 2 2 - (5-Acetyl-2-butoxy-3-pyridinyl) -7-ethyl-5-propylimidazo [5,1- Compound of the title compound of preparation 24 (70 mg, 0.145 mraol), butyl vinyl ether (0.30 ml, 2.3 mmol), tri-o-tolylphosphine (10 mg, 0.06 mmol), triethylamine ( 0.05 mL, 0.36 mmol) and Pd (0A) 2 (6 mg, 0.03 mmol) in eCN (2 mL) and the mixture was refluxed for 5 hours and then cooled. 6 M HCl (1 mL) was added and the mixture was stirred for 15 minutes. Water (40 ml) was added and the solution was extracted with EtOAc (50 ml). This was dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by column chromatography (DCM / MeOH, 99.25: 0.75 to 98.5: 1.5)) and triturated with diisopropyl ether, yielding the title compound as a beige solid (14). tng, 0.035 mmol, 24%); p.f. 155-156 ° C. ¾ RM (400 MHz, CDC13): 5 = 9.75 (sa, 1H), 9.00 (s, 1H), 8.90 (s, 1H), 4.65 (t, 2H), 3.10 (g, 2H), 3.00 (t, 2H), 2.65 (s, 3H), 1.90 (pentete, 2H), 1.80 (sextet, 2H), 1.55 (m, 2H) , 1.40 (t, 3H), 1.00 (2 overlapping triplets, 6H). LCMS (ES +): m / z 398 (MH +). High resolution MS: m / z calculated for C2iH27Ns03: 398.2187; found: 398.2177 (MH +). Example 3 2- (5-Acetyl-2-butoxy-3-pyridinyl) -7-ethyl-5- (4-morpholinylmethyl) imidazo G5, 1-G? G? , 2, 41 triazin-4 (3H) -one Compound the title compound of Preparation 26 (45 mg, 0.0835 mmol), butyl vinyl ether (0.18 mL, 1.38 mmol), tri- or-tolylphosphine (14 mg, 0.046 mmol), triethylamine ( 0.03 ml, 0.215 mmol) and Pd (0Ac) 2 (5 mg, 0.0223 mmol) in eCW (1 ml) and the mixture was refluxed for 5 hours and then cooled. The mixture was partitioned between DCM (30 mL) and a saturated solution of NaHCO 3 (25 mL) and the aqueous phase was further extracted with DCM (2 x 20 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo- The crude product was purified by column chromatography (DCM / MeOH, 98: 2 to 92: 8) and trituration with diisopropyl ether, yielding the title in the form of a beige solid (15 mg, 0.033 mmol, 39%); p.f. 145-149 ° C. ¾ NMR (400 MHz, CDC13): d = 9.90 (sa, 1H), 9.10 (s, 1H), 8.90 (s, 1H), 4.70 (t, 2H), 4.00 (s, 2H), 3.75 (m, 4H), 3.10 (q, 2H), 2.65 (m, 4H), 2.65 (darkened singlet, 3H), 1.95 (pentete, 2H) ), 1.60 (m, 2H), 1.45 (t, 3H), 1.05 (t, 3H). CLE (ES +): m / z 455 (MH +). Biological Activity The preferred compounds of formula (I) of this invention have riv vi activities as inhibitors of cGMP PDE5 with IC 50 values of less than about 10 nM. The compounds of Examples 1 and 2 of this invention have IC50 values of cGMP PDE5 (from human corpora cavernosa) of 1.34 nM and 1.96 nM respectively. In vitro metabolism data Table 1 illustrates the increase in half-life in HLM of the compound of example 1 versus a compound A of a comparative example.

Example HLM tJ / 2 (min.) 1 21 Compound A 4 Compound A is 2- [2-ethoxy-5- (4-ethylpiperazin-1-yl-1-sulfonyl) -phenyl] -5-methyl-7-propyl-3H-imidazo [5, 1 -f] [1 , 2,4] triazin-4-one also known as 1- [[3- (3,4-dihydro-5-methyl-4-oxo-7-propylimidazo [5,1-f] -as-triazin- 2-yl) -4-ethoxyphenyl] sulfonyl] -4-ethylpiperazine. Compound A can be prepared according to the procedures detailed in examples 20, 19, 337 and 336 of the publication of the international patent application W099 / 24433.

Claims

1. A compound of general formula I: or pharmaceutically or veterinarily acceptable salts, solvates, polymorphs or prodrugs thereof, wherein: A represents CHOH or C = 0; X represents O or NR5; Y represents CH or N; R1 and R2 independently represent H, C ^ -Q alkyl, Het, Cj-Cu-Het alkyl, aryl, C ^ -e-aryl alkyl, halo-, cyano, nitro, OR6, OC (0) R6, C (0 ) R6, C (0) OR6, NR6C (0) NR7R8, NR6C (0) OR6, OC (0) NR7R8, C (0) NR9R10, NR9R10, S02NR9R10 or S02Ru; R3, R4 and R5 independently represent H, C ^ -Cg alkyl, Het, Cj-Cg-Het alkyl, aryl or Cj-Q-aryl alkyl; or R3 and R5, together with the nitrogen atom to which they are attached, can form a heterocyclic ring that is optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12-, 0C (0) R12, C (0) R12, C (0) OR12, NR, 2C (0) NR13R14, NR, 2C (0) OR12, OC (O) R13R14, C (0) NR15R16, NR15R16, S < ¾NR15R16 or S02R17; wherein, when R1, R2, R3, R4 or R5 is a C, -C6, Het, alkyl aryl or Cj-Cg-aryl alkyl group, such alkyl group Cj-Cg, Het, alkyl C [-C6-] Het, aryl or QQ-aryl alkyl may be optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR6, 0C (0) R6, C (0) R6, C (0) 0R6 , NR6C (O) NR7R8, NR6C (0) OR6, OC (0) NR7R8, C (O) R9Ri0, NR9R10, S02NR9R10, S02Rn, C ^ C ^ alkyl, Het, alkyl Cj-C67 Het, aryl or alkyl in the that when R1, R2, R3, R4 or R5 is an alkyl group Cj ~ C6, Het, alkyl Cj-C6-Het, aryl or alkyl Cj-Ce-aryl which is substituted and / or terminated with one or more substituents selected from : C ~ C6 alkyl, Het, alkyl-Cg-Het, aryl or C 1 -C 6 -alkyl alkyl, such substituent groups are optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12 , 0C (0) R12, C (0) R12, C (0) 0R12, NR12C (O) NRI3R14, NR12C (0) OR12, OC (0) NR13R14, C (0) NR15R16, NR15R16, S02NR15R16 or S02R] 7; R6, R7 and R8 independently represent H, Cj-C6 alkyl, Het, Ci-C6 alkyl-Het, aryl or Q-Q-aryl alkyl; or R7 and R8, together with the nitrogen atom to which they are attached, can form a heterocyclic ring that is optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12, 0C (0) R12, C (0) R12, C (0) 0R12, NR] 2C (0) NR! 3R14, NR12C (0) OR12, OC (0) NR13R14, C (0) NR15R16, NR, 5R16, S02NR15R16 or S02R17; R9 and R10 independently represent H, C (0) R6, S02Rn, alkyl Q-Cg, Het, alkyl Cj-Cg-Het, aryl or C [-C6-aryl] alkyl; or R9 and R10, together with the nitrogen atom to which they are attached, can form a heterocyclic ring that is optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12, OC (0) R12, C (0) R12, C (0) OR12, NR12C (0) NR13R14, NR12C (0) OR12, 0C (O) NR13R14, C (0) NR15R16, RR15R16, S02NR15R16 or S02R17; R 11 represents alkyl-Cg, Het, alkyl Q-C-Het, aryl or Cj-Cg-aryl alkyl; wherein, when R6, R7, R8, R9, R10 or Rn is a C ^ -8 alkyl group, Het, C ^ -Cg-Het alkyl, aryl or Cj-C6-alkyl aryl, such C-alkyl group, C6, Het, alkyl -Cg-Het, aryl or C C-C6 alkyl aryl may be optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12, 0C (0) R12, C (0) R12, C (0) 0R12, R12C (O) NR3R14, NR12C (0) OR12, 0C (O) NR13RM, C (0) NR15R16, NR15R16, S02NR15R16 or S02R17; Rir, R13 and R14 independently represent H or C] -C6 alkyl; or R13 and R14, together with the nitrogen atom to which they are attached, can form a heterocyclic ring; R15 and R16 independently represent H, C (0) R12, S02R or C ^ Q alkyl or R15 and R16, together with the nitrogen atom to which they are attached, can form a heterocyclic ring; R17 represents C] -C6 alkyl; and wherein Het represents an optionally substituted heterocyclic group of four to twelve members, said group containing one or more heteroatoms selected from nitrogen, oxygen, sulfur and mixtures thereof; with the proviso that when Y is CH, and X is 0 and? is C (O), then each of R1, R3 and R4 does not represent C-C6 alkyl and R2 does not represent Cj-C6 alkyl or C3-Cfi cycloalkyl; and with the additional proviso that when Y is CH, and X is O and A is CH (OH), then each of R1 and R3 does not represent Cj-C6 alkyl and R2 does not represent Cx-C6 alkyl or C3-C6 cycloalkyl and R 4 is not phenyl or C 1 -C 5 alkyl optionally substituted with up to 2 substituents selected from hydroxy, phenyl, NR 9 R 10 or OC (0) R 6, where R 9 and R 10 are H groups, (C, -C 6) alkyl, alkyl. { Cx-C6) -phenyl or phenyl optionally substituted with hydroxy or OR12 and R6 being alkyl (Cj-Cfi) optionally substituted with a halogen or OR.12, and OR12 being O-alkyl (C, -C6).

2. Compound as defined in claim 1, wherein: A represents CHOH or C = 0; X represents 0; Y represents CH or N; R1, R2, R3 and R4 independently represent C, -C6 alkyl, Het, Cj-Cg-Het alkyl, aryl or C -C6 alkyl-aryl optionally substituted and / or terminated with one or more substituents selected from: halo-, OR6, NR9R10, C, -C6 alkyl, Het, Cj-C6 alkyl-Het, aryl or Ci-C6 alkyl aryl; wherein when R1, R2, R3 or R4 is a C, -C6, Het, alkyl Ci-C6-Het alkyl, aryl or alkyl group that is substituted and / or terminated with one or more substituents selected from: -C alkyl , Het, alkyl C, -Cg ~ Het, aryl or Ci-C6 alkyl aryl, such substituents are optionally substituted and / or terminated with one or more additional substituents selected from: halo-, OR12 or NR15R16; wherein R6, R9, R10, R12, R15 and R16 are as defined in claim 1; with the proviso that when Y is CH, and X is O and A is C (0), then each of R1, R3 and R4 does not represent Cl-C6 alkyl and R2 does not represent Cx-C6 alkyl or C3-C6 cycloalkyl , and with the additional proviso that when Y is CH, and X is O and A is CH (OH), then each of R1 and R3 does not represent C: -6 alkyl and r2 does not represent -CG alkyl or C3-cycloalkyl- C6 and R4 is not phenyl or Cj-C5 alkyl optionally substituted with up to 2 substituents selected from hydroxy, phenyl, NR9R10 or OC (0) R6, where R9 and R10 are H groups, alkyl (Cj-Cg), alkyl (C, - C <) -phenyl or phenyl optionally substituted with hydroxy or OR12 and wherein R6 is alkyl (C, -C6) optionally substituted with a halogen or OR12, and wherein OR12 O-alkyl is (Cx-C6).

3. Compounds as defined in claim 1: wherein A represents CHOH or C = 0; X represents 0; And represents N; R 1, R 2, R 3 and R 4 independently represent C 1 Cg alkyl, Het, C 1 Cg-Het alkyl, aryl or C 1 -C 6 alkyl aryl optionally substituted and / or terminated with one or more substituents selected from: halo-, OR 6 , R 9 R 10, C 1 -C 6 alkyl, Het, C 1 -C 6 alkyl, Het, aryl or C 1 -C 4 alkyl aryl wherein when R 1, R 2, R 3 or R 4 is a C, -C 6 alkyl, Het, alkyl C group ^ -Cfi-Het, aryl or Ci-C6 alkyl aryl which is substituted and / or terminated with one or more substituents selected from: Cj- alkyl, Het, alkyl-Cg-Het, aryl or Ci-C6 alkyl aryl, such substituents are optionally substituted and / or terminated with one or more additional substituents selected from: halo-, 0Ri2 or NR15R16; wherein R6, R9, R10, R12, R13 and R161 »are as defined above in this document.

4. Compounds according to any of claims 1 to 3, wherein A represents C = 0.

5. Compounds of general formula (I) as defined above in this document, in which: A represents C = 0; X represents O or NR5; Y represents CH or N; R1 and R2 independently represent H, Het, C, -C6-Het alkyl, aryl, C, -C6-aryl, halo-, cyano, nitro, OR6, OC (0) R6, C (0) R6, C ( 0) OR6, NR6C (0) NR7R8, NR6C (0) OR6, OC (0) NR7RS, C (0) NR9R10, NR9R10, S02NR9R10 or S02Rn; R3 and R4 independently represent H, Het, alkyl-C8-Het, aryl or C, -C6-alkyl aryl; R5 independently represents H, Cj-Q alkyl, Het, C, -C6-Het alkyl, aryl or Cj-Cg-aryl alkyl; or R3 and R5, together with the nitrogen atom to which they are attached, can form a heterocyclic ring that is optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12, OC (0) R12, C (0) R12, C (0) OR12, NR12C (0) NR13R14, NR12C (0) OR12, 0C (O) NR13R14, C (0) NR15R16, NR15R! 6, S02NR! 5R16 or S02R17; wherein when R1, R2, R3 or R4 is a group, Het, alkyl Cj-Q-Het, aryl or alkyl Cj-Q-aryl, such group ^ Het, alkyl C ^ -Cg-Het, aryl or Cj alkyl -C6-aryl may be optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR6, 0C (0) R6, C (0) R6, C (0) 0R6, NR6C ( O) NR7R8, NR6C (0) OR6, OC (0) NR7R8, C (0) NR9R10, NR9R10, S02NR9R10, S02Ru, C, -C6 alkyl, Het, alkyl C, -C6-Het, aryl or Cj-Cg-aryl alkyl wherein when R1, R2, R3 or R4 is a group Het, alkyl C] -C6-Het, aryl or alkyl Cj-C6- aryl that is substituted and / or terminated with one or more substituents selected from: Ci-Ce alkyl, Het, C, -C6-Het alkyl, aryl or Cj-Cg-aryl alkyl, such substituent groups are optional. Completely substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12, 0C (0) R12, C (0) R12, C (0) 0R12, NR12C (O) R13R14, NR12C (O ) OR12, OC (0) NR13R14, C (0) NR15R16, NR15R16, S02NRI5R16 or S02R17; wherein when R 4 is a group, Het, alkyl Ci-Cg-Het, aryl or C-C 1 alkyl alkyl, such C 6 -C 6 alkyl, Het, alkyl d-C 8 He, aryl or C 6 -C 6 alkyl group aryl may be optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR6, OC (0) R6, C (0) R5, C (0) OR6, NR6C (O) NR7R8, NR6C (0) OR6, OC (0) NR7R8, C (0) MR9R10, NR9R10, S02NR9R10, S02Rn, CX-C6 alkyl, Het, alkyl Q-Ce-He, aryl or alkyl C ^^ -aryl; wherein when R5 is a group 'C6 alkyl, Het, CX-C6 alkyl, Het, aryl or C ^ -Q-aryl alkyl, which is substituted and / or terminated with one or more substituents selected from: Cj alkyl -C ^; Het, C 1 -Cg-Het alkyl, aryl or C 1 -C 5 -C alkyl alkyl, such substituent groups are optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR 12, OC (0) R 12 , C (0) R12, C (0) OR12, NRI2C (O) NR13R14, NR12C (0) OR12, OC (0) NR13RM, C (0) NRl5Rls, NR15R1 < 5, S02NR15RIa or S02R17; R6, R7 and R8 independently represent H, Cl-C6 alkyl, Het, C 1 -Cg-Het alkyl, aryl or C 1 -C 6 alkyl aryl; or R7 and R8, together with the nitrogen atom to which they are attached, can form a heterocyclic ring that is optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, 0Ri2, OC (0) R12, C (0) R12, C (0) 0R12, NR12C (0) NRl3R14, NR12C (O) OR12, 0C (O) NR13R14, C (0) NR15R'6, NR15R16, S02NRl5R16 or S02R17; R9 and R10 independently represent H, C (0) R6, S02Rn, alkyl C! -C6, Het, Ci-C6 alkyl Het, aryl or Ct-C6 alkyl aryl or R9 and R10, together with the nitrogen atom to which they are attached, can form a heterocyclic ring which is optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR11, OC (0) R12, C (0) Ru, C (0) OR12, NR12C (0) NR13R14, R12C (O) OR12, OC ( O) NR13R14, C (0) R15R16, R15R16, S02 R15R16 or S02R17; R n represents alkyl Cj-Cg, Het, alkyl Cj-Q-Het, aryl or C, -C6-aryl alkyl; wherein when R6, R7, R8, R9, R10 or R11 is a C C alkyl group, Het, C C-C6 alkyl, Het, aryl or C C-aryl alkyl, such alkyl groups 0, -06, Het, alkyl Cj-C6-Het, aryl or Ci-C6 alkyl aryl may be optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12, OC (0) R12, C ( 0) R12, C (0) OR12, NR12C (O) NR13R14, NRI2C (O) OR12, OC (O) NR13R14, C (0) NR15R16, R15R16, S02NR15R16 or S02R17; R12, R13 and R14 represent independently? or C] -C6 alkyl; or R13 and R14, together with the nitrogen atom to which they are attached, can form a heterocyclic ring; R15 and R16 independently represent H, C (0) R12, S02R17 or Cj-C6 alkyl; or R15 and R15, together with the nitrogen atom to which they are attached, can form a heterocyclic ring; R17 represents C ^ -Ce alkyl; wherein Het represents an optionally substituted four- or twelve-membered heterocyclic group, said group containing one or more heteroatoms selected from nitrogen, oxygen, sulfur and mixtures thereof.

6. Compounds according to any of claims 1 to 4, wherein Y is N and A is C (O) and R1, R2, R3, R4 and R5 are independently selected from C, -C4 or C2 alkyl. -C4-Het.

7. Compounds according to any one of claims 1 to 4 or 6, wherein Y is N and A is C (0) and R1 is Cx-C4 alkyl or Ci-C4 alkyl-Het, R2, R5 and R4 are independently alkyl C ^ -C6, and R3 is C2-C4 alkyl.

8. Compounds according to any of claims 1 to 4, or 6 or 7, wherein Het is selected from ring systems of 5 to 8 members (C5-C8) which contain at least one N and optionally O, S or mixtures thereof.

9. Compounds according to any of the preceding claims selected from: 2- (5-Acetyl-2-butoxy-3-pyridinyl) -7-ethyl-5-methylimidazo [5,1- f] [1,2,4] triazine -4 (3ff) -one; 2- (5-Acetyl-2-butoxy-3-pyridinyl) -7-ethyl-5-propylimidazo [5, 1-f] [1,2,4] triazin-4 (3-yl) -one; 2- (5-Acetyl-2-butoxy-3-pyridinyl) -7-ethyl-5- (4-morpholinyl-methyl) imidazo [5, 1-f] [1, 2, 4] triazin-4 (3H) -one; or 2- (5-Acetyl-2-butoxy-3-pyridinyl) -7-ethyl-5- (4-morpholinyl ethyl) imidazo [5, 1-f] [1,2,4] triazin-4 (3) ) -one and pharmaceutically acceptable salts, solvates and prodrugs thereof.

Compounds of general formula or pharmaceutically or veterinarily acceptable salts, solvates, polymorphs or prodrugs thereof, wherein: A represents CHOH or C = 0; \ X represents O or NR5; Y represents CH or N R1 and R2 independently represent H, C-C6 alkyl, Het, C, -C6-Het alkyl, aryl, C1-C6 alkyl-aryl, halo-, cyano, nitro, OR6, OC (0) R6 , C (0) R6, C (0) OR6, WR6C (O) R8, NR6C (0) OR6, OC (0) NR7R8, C (0) NR9R10, NR9R10, S02NR9R10 or S02R! 1; R 3, R 4 and R 5 independently represent H, C 1 Cg alkyl, Het, C 1 -C 6 alkyl, Het, aryl or C 1 -C 6 alkyl aryl; or R3 and R5, together with the nitrogen atom to which they are attached, can form a heterocyclic ring that is optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12, OC (0) Rl2i C (0) R12, C (0) OR12, NR12C (0) NR13R14, NR12C (O) OR12, OC (0) NR13R14, C (0) R, 5R16, R15R16, S02NRI5R16 or S02Rn; wherein, when R 1, R 2, R 3, R 4 or R 5 is a C 1 -C 6 alkyl, Het, C 1 Q-Het alkyl, aryl or C 1 -Cg-aryl alkyl group, such C, -C 6 alkyl group, Het, alkyl Q-Cg-Het, aryl or C ^-^ -aryl alkyl may be optionally substituted and / or terminated with one or more substituents selected from: halo- / cyano, nitro, OR6, OC (0) R6 C (0) R6, C (0) OR6, NR6C (0) NR7R8, NR6C (0) OR6, OC (0) NR7R8, C (0) NR9R10, R9R10, S02NR9R10, S02Rn, C, -C6 alkyl, Het, alkyl C ^ C8-Het, aryl or C 1 -Cg-aryl alkyl; wherein when R1, R2, R3, R4 or R5 is a Cx-C6 alkyl group, Het-; alkyl C ^ -Cg-Het, aryl or Cj-Cg-aryl alkyl which is substituted and / or terminated with one or more substituents selected from: C] -C6 alkyl, Het, C6-Cet alkyl, Het, aryl or alkyl- Q-aryl, such substituent groups are optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12, 0C (0) R12, C (0) Rn, C (O) OR12, NR12C (O) NR13R14, R12C (0) OR12, OC (0) NRI3R14, C (O) NRl3R16, NR, 5R16, S02NR15R16 or S02R17; R6, R7 and R8 independently represent H, C ^ -Cg alkyl, Het, Cj-Ce-Het alkyl, aryl or Ci-C6 alkyl aryl; or R7 and R8, together with the nitrogen atom to which they are attached, can form a heterocyclic ring which is optionally substituted and / or terminated with one or more substituents selected from among-, halo-, cyano, nitro, OR12, OC ( ) R12f C (0) R12, C (0) 0R12, NR12C (0) NRI3R14, NRI2C (O) OR12, OC (O) NR13R14, C (0) NRISR16, NR15R16, S02NR15R16 or S02R17; R9 and R10 independently represent H, C (0) R6, S02Ru, Cj-C6 alkyl, Het, Cj-Cg-Het alkyl, aryl or Ci-C6 alkyl aryl; or 9 and R10, together with the nitrogen atom to which they are attached, can form a heterocyclic ring which is optionally substituted and / or terminated with one or more substituents selected from: halo-, cyano, nitro, OR12, OC ( ) R12, C (0) R12, C (0) OR12, NR12C (0) NR13R14, NR12C (O) OR12, OC (0) NR13R14, C (0) NR15R16, NR15R16, S02WR15R16 or S02R17; Ru represents alkyl Cj-Cg, Het, alkyl C, -C6-Het, aryl or alkyl-C-aryl; wherein, when R6, R7, R8, R9, R10 or Rn is a Ci-C6 alkyl group ". Het, alkyl Cj-C6-Het, aryl or C, -C6-alkyl aryl, such C-C6 alkyl, Het, C-Cg-Het alkyl, aryl or alkyl group may be optionally substituted V / ° terminated with one or more substituents selected from: halo-, cyano, nitro, OR12, 0C (0) R12, C (0) R12, C (0) 0R12, NR12C (O) NR13R14, NR12C (O) OR12, OC (O) NR13R14, C (0) NR15R16, NRI5R16, S02NRI5R16 or S02R17; R12, R13 and R14 independently represent H or C ^ -Cg alkyl; or R13 and R14, together with the nitrogen atom to which they are attached, can form a heterocyclic ring; R15 and R, fi independently represent H, C (0) R12, S02R17 or C-C6 alkyl; or R15 and R16, together with the nitrogen atom to which they are attached, can form a heterocyclic ring; R17 represents alkyl Cj, -C6; Het represents an optionally substituted four to twelve membered heterocyclic group, said group containing one or more heteroatoms selected from nitrogen, oxygen, sulfur and mixtures thereof.

11. Compounds according to any of the preceding claims, for use as a pharmaceutical agent.

12. Compounds as defined in any of the preceding claims, for use as an animal medicament.

13. A formulation comprising a compound as defined in any one of the preceding claims (in admixture with a pharmaceutically or veterinarily acceptable adjuvant, diluent or carrier.

14. A formulation according to claim 13, which is a pharmaceutical formulation.

15. A formulation according to claim 13, which is a veterinary formulation.

16. The use of a compound as defined in any of the preceding claims in the manufacture of a medicament for the curative or prophylactic treatment of a medical condition for which the inhibition of cGMP PDE5 is desired.

17. A method of treating or preventing a medical condition for which inhibition of cGMP PDE5 is desired, which comprises administering a therapeutically effective amount of a compound according to any of the preceding claims to a patient in need of such treatment. 18, Use according to claim 16, or method according to claim 17, wherein the condition is male erectile dysfunction (MED), impotence, female sexual dysfunction (PSD), clitoral dysfunction, sexual desire disorder hypoactive female, female sexual arousal disorders, female sexual pain disorder and female sexual orgasmic dysfunction (FSOD).