Drugs for sex dysfunctions

Use for the treatment of sex dysfunctions of one or more of the following classes of drugs:

• A) salified and non salified nitric oxide donor drugs, of formula
• A—X1—N(O)z
• wherein the meaning of the terms appearing in the formula is as defined hereunder;
• C) nitrate salts of compounds inhibiting phospho-diesterases;
• in the compounds of general formula:
• A—X1—N(O)z
• z is an integer and is 1 or 2, preferably 2;
• A=R(COXu)t and wherein t is an integer 0 or 1;
• u is 0 or 1;
• X=O, NH, NR1c wherein R1c is a linear or branched C1-C10 alkyl;
• X1 is the following bivalent linking group:
• 17
• wherein:
• nIX is an integer in the range 0-3;
• nIIX is an integer in the range 1-3;
• RTIX, RTIX′, RTIIX, RTIIX′ equal to or different from each other are H or a linear or branched C1-C4 alkyl;
• Y is an heterocyclic ring containing one or two nitrogen atoms, optionally one oxygen or sulphur atom, said saturated, unsaturated or aromatic ring having 5 or 6 atoms;
• R of the radical A of formula A—X1—N(O)z is selected from the following groups:
• Group I) wherein t=1 and u=1
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• wherein:
• R1 is the OCOR3 group;
• wherein R3 is methyl, ethyl or a linear or branched C3-C5 alkyl, or the residue of an heterocycle having only one ring having 5 or 6 atoms which can be aromatic, partially or totally hydrogenated, containing one or more hetero-atoms independently selected from O, N and S;
• R2 is hydrogen, hydroxy, halogen, linear or branched C1-C4 alkyl, linear or branched C1-C4 alkoxy;
• a linear or branched C1-C4 perfluoroalkyl, for example trifluoromethyl;
• nitro, amino, mono- or di-(C1-4) alkylamino;
• nI is an integer 0 or 1;
• group II) wherein t=1, u=1
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• wherein:
• RII5 is H, linear or branched when possible C1-C3 alkyl;
• RII6 has the same meaning as RII5, or when RII5 is H it can be benzyl;
• RII1, RII2 and RII3 can independently be hydrogen, linear or branched when possible C1-C6 alkyl, or linear or branched when possible C1-C6 alkoxy, or Cl, F, Br;
• RII4 is RII1, or bromine;
• IIb) is the residue of the 2-[(2-methyl-3-(trifluoromethyl)phenyl]amino]-3-pyridincarboxylic]acid and when the —COOH group is present it is known as flunixin;
• group III) wherein t=1, u=1 and R is
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• wherein:
• R2a and R3a are H, linear or branched when possible, substituted or not, C1-C12 alkyl or allyl, with the proviso that if one of the two is allyl the other is H;
• preferably R2a is H, C1-C4 alkyl, R3a is H;
• R1a is selected from
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• IIID) R1a corresponds to the following formulas:
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• wherein the meanings are the following:
• when R1a is as defined in formula (IV), Ketoprofen residue:
• RIII1 is H, SRIII3 wherein RIII3 contains from 1 to 4 carbon atoms, linear or branched when possible;
• RIII2 is H, hydroxy;
• when R1a is as defined in formula (XXI), carprofen residue:
• Rxxio is H, linear or branched when possible alkyl from 1 to 6 carbon atoms, C1-C6 alkoxycarbonyl linked to a C1-C6 alkyl, C1-C6 carboxyalkyl, C1-C6 alkanoyl, optionally substituted with halogens, benzyl or halobenzyl, benzoyl or halobenzoyl;
• Rxxi is H, halogen, hydroxy, CN, C1-C6 alkyl optionally containing OH groups, C1-C6 alkoxy, acetyl, benzyloxy, SRxxi2, wherein Rxxi2 is C1-C6 alkyl;
• C1-C3 perfluoroalkyl;
• C1-C6 carboxyalkyl optionally containing OH groups, NO2, amino;
• sulphamoyl, di-alkyl sulphamoyl with C1-C6 alkyl or difluoroalkyl-sulphonyl with C1-C3 alkyl;
• Rxxi1 is halogen, CN, C1-C6 alkyl containing one or more OH groups, C1-C6 alkoxy, acetyl, acetamido, benzyloxy, SRIII3 being RIII3 as above defined, C1-C3 perfluoroalkyl, hydroxy, C1-C6 carboxyalkyl, NO2, amino, mono- or di-alkyl-amino C1-C6;
• sulphamoyl, di-alkyl sulphamoyl C1-C6, or di-fluoroalkylsul-phamoyl as above defined;
• or Rxxi, together with Rxxi1 is an alkylen dioxy C1-C6;
• when R1a is as defined in formula (XXXV) tiaprofenic acid residue:
• Ar is phenyl, hydroxyphenyl optionally mono or polysubstituted with halogen, alkanoyl and alkoxy C1-C6, trialkyl C1-C6, preferably C1-C3, cyclopentyl, cyclohexyl, cycloheptyl, heteroaryl, preferably tienyl, furyl optionally containing OH, pyridyl;
• when R1a is as defined in formula (II), suprofen residue, wherein R3a is H, R2a is methyl and X=O;
• when R1a is as defined in formula (VI), R is the residue of indoprofen when R2a=H and R3a=CH3;
• of indobufen when R2a is equal to H and R3a=C2H5;
• X=O;
• when R1a is as defined in formula (VIII) R is the etodolac residue when R2a=R3a=H and X=O;
• when R1a is as defined in formula (VII), R is the fenoprofen residue when R3a=H, R2a=CH3 and X=O;
• when R1a is as defined in formula (III), R is the fenbufen residue when R2a=R3a=H and X=O;
• when R1a is as defined in formula (IX), R is the flurbiprofen residue when R3a =H, R2a=CH3, X=O;
• when R1a is as defined in formula (X) R is the tolmetin residue when , R2a=R3a=H, X=O;
• in group IIID) R1a corresponds to the following formulas:
• IIIa), when R2a=H and R3a=CH3 the pranoprofen residue is obtained:
• α-methyl-5H-[1]benzopyran-[2,3-b]pyridin-7-acetic acid;
• the preferred compound has R2a=H, R3a=CH3, u=1 and X=O:
• (XXX), when R2a=H and R3a=CH3 the bermoprofen residue is obtained:
• dibenz[b,f]oxepin-2-acetic acid;
• (XXXI), when R2a=H and R3a=CH3, R is the radical of the CS-670 compound:
• 2-[4-(2-oxo-1-cyclo-hexyliden methyl) phenyl]propionic acid;
• (XXXII), when R2a=R3a=H the Pemedolac residue is obtained;
• (XXXIII), when R2a=R3a=H the pirazolac residue is obtained:
• 4-(4-chlorophenyl)-1-(4-fluoro phenyl)-3-pyrazolic acid;
• (XXXVI), when R2a=H, R3a=CH3 the zaltoprofen residue is obtained;
• when the residue is saturated with an hydroxyl or amino group, or with the carboxylic function the compounds are known as dibenzothiepine derivatives;
• (XXXVII), when R2a=R3a=H the mofezolac residue is obtained:
• 3,4-di(p-methoxyphenyl)isoxazol-5-acetic acid;
• (XII), when R2a=R3a=H the bromfenac residue is obtained:
• 2-amino-3-(4-bromobenzoyl)benzeneacetic acid;
• in group IV) wherein t=1, u=1, R is
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• wherein:
• RIVd and RIVd1 are at least one H and the other a linear or branched C1-C6, preferably C1 and C2 alkyl, or difluo-roalkyl with the alkyl from 1 to 6 carbon atoms, C1 is preferred, or RIVd and RIVd1 form together a methylene group;
• RIV has the following meaning:
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• wherein the compounds of group IV) have the following meanings:
• in formula (II):
• Riv-ii is C1-C6 alkyl, C3-C7 cycloalkyl, C1-C7 alkoxy-methyl, C1-C3 trifluoroalkyl, vinyl, ethynyl, halogen, C1-C6 alkoxy, difluoroalkoxy, with C1-C7 alkyl, C1-C7 alkoxymethyloxy, alkylthio methyloxy with C1-C7 alkyl, alkyl methylthio with C1-C7 alkyl, cyano, difluoromethylthio, phenyl- or phenylalkyl substituted with C1-C8 alkyl.
• formula (X) loxoprofen residue;
• in formula (III):
• Riv-iii is a C2-C5 alkyl, optionally branched when possible, C2 and C3 alkyloxy, allyloxy, phenoxy, phenylthio, cycloalkyl from 5 to 7 carbon atoms, optionally substituted in position 1 by a C1-C2 alkyl;
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• In group V):
• when R is formula (II), Rvii is H or a linear or branched C1-C4 alkyl;
• Rvii-1 is Rvii, or a linear or branched C1-C4 alkoxy;
• Cl, F, Br;
• the position of Rvii-1 being ortho, or metha, or para;
• when R is formula (V),
• of which the residue of the known tenidap has been indicated;
• When R is formula (V) A=R and t=O,
• when R is formula (VII), A is RCO, t=1 u=0 or A is R and t=0;
• when R is formula (IX), A=R and t=0, or A=RCO with t=1 and u=0;
• when R is formula (III) A=RCOO, t=1 and u=0 or 1;
• or t=0 and A=R;
• when R is formula (IV) A=RCOO, t=1 and u=1;
• when R is formula (IX) and in (COXu)t u=t=1 and X is oxygen, the precursor compound is sulindac;
• when R is formula (X) it is the meloxicam residue;
• when R is formula (XI) the residue is known as ampiroxicam when the termination is —CH(CH3)OCOC2H5;
• when R is formula (XIII) and the valence is saturated with H, the residue derives from lornoxicam;
• when R is formula (XXXX) and the valence is saturated with H the compound is known as paracetamol;
• when R is formula (XXXXI) and the valence is saturated with H the compound is known as tramadol.