Drugs for chronic pain

1. Nitrooxyderivatives or salts thereof of formula (I)

R—NR 1c —(K) k0 —(B) b0 —(C) c0 —NO 2   (I)

wherein

c0 is 1

b0 is 0;

k0 is 0;

R 1c is H

C=bivalent radical of formula —T c —Y

wherein

T c =(CO); and

Y is an alkylenoxy group —R′O— in which R′ is straight or branched C 1 -C 20 alkyl, a cycloalkylene with from 5 to 7 carbon atoms, or

wherein n3 is an integer from 0 to 5 and n3′ is an integer from 1 to 3;

R is a radical of an analgesic drug of formula (II):

wherein:

W is a carbon atom;

m is 1;

R 0 =—(CH 2 ) n —COOR y , wherein R y =H, C 1 -C 10 -alkyl, phenyl, or benzyl;

n is an integer of from 0 to 2;

R 1 =H

R 2 is selected from the following groups:

phenyl, optionally substituted with a halogen atom or with a group selected from —OCH 3 , —CF 3 , nitro

or dihydroxy-substituted benzyl;

amidino group: H 2 N(C═NH)—;

a radical of formula (IIA), wherein optionally an ethylenic unsaturation may be present between the carbon atoms in position 1 and 2, or 3 and 4 or 4 and 5:

wherein:

p, p 1 , p 2 are integers, same or different, and are 0 or 1;

p 3 in an integer of from 0 to 10;

R 4 is hydrogen, straight or branched C 1 -C 6 -alkyl, free valence;

R 5 is:

hydrogen,

straight or branched C 1 -C 6 -alkyl,

C 3 -C 6 -cycloalkyl, or

OR A , wherein R A is:

straight or branched C 1 -C 6 -alkyl, optionally substituted with one or more halogen atoms, or

phenyl optionally substituted with a halogen atom or with one of the following groups: —OCH 3 , —CF 3 , nitro;

R 6 , R 6A , R 7 , R 8 , the same or different, are H, methyl or free valence, with the proviso that when an ethylenic unsaturation is present between C 1 and C 2 in radical of formula (IIA), R 4 and R 5 are free valences able to form the double bond between C 1 and C 2 ; if the unsaturation is between C 3 and C 4 , R 6 and R 7 are free valence able to form the double bond between C 3 and C 4 ; is the unsaturation is between C 4 and C 5 , R 7 and R 8 are free valence able to form the double bond between C 4 and C 5 ;

Q is H, OH, OR B , R B being benzyl, straight or branched C 1 -C 6 -alkyl, optionally substituted with one or more halogen atoms, preferably F, phenyl optionally substituted with a halogen atom or with one of the following groups: —OCH 3 , —CF 3 , nitro; or

Q is

—C 3 -C 6 -cycloalkyl,

guanidino (H 2 NC(═NH)NH—), or

thioguanidino (H 2 NC(═S)NH—),

in formula (II) R 2 with R 1 and with W═C form together a C 4 -C 10 saturated or unsaturated ring.

2. Compounds according to claim 1 , wherein in formula (I):

Y is:

an alkylenoxy group —R′O— in which R′ is straight or branched C 2 -C 6 alkyl; or

wherein n3 is an integer from 0 to 3 and n3′ is an integer from 1 to 3;

R is the radical of an analgesic drug of formula (II):

wherein:

W is a carbon atom;

m is 1

R 0 =—(CH 2 ) n —COOH, wherein n is an integer of from 0 to 2;

R 1 =H;

R 2 is selected from the following groups:

3,4-dihydroxybenzyl; or

a radical of formula (IIA) as defined in claim 1 , wherein:

p and p 1 are 0 or 1;

p 2 and p 3 are 0;

R 4 and R 5 are hydrogen, straight or branched C 1 -C 6 -alkyl or free valence;

R 6 and R 6A are H;

with the proviso that when an ethylenic unsaturation is present between C 1 and C 2 in radical of formula (IIA), R 4 and R 5 are free valences able to form the double bond between C 1 and C 2 ;

Q is H, CH 3 or

guanidino (H 2 NC(═NH)NH—), or

thioguanidino (H 2 NC(═S)NH—);

in formula (II) R 2 with R 1 and with W form together a C 6 saturated ring.

3. Compounds according to claim 1 , wherein when in formula (II) W=C, m=1 and R 0 =—(CH 2 ) n —COOR y , wherein n=1 and R 7 =H; R 2 and R 1 with W as defined above form the cyclohexane ring; the drug precursor of R having the formula R—NH 2 is known as gabapentin;

when in formula (II) W=C, m=1 and R 0 if defined as for gabapentin with n=1; R 1 =H; R 2 is the radical of formula (IIA) in which p=p 1 =p 2 =p 3 =0, R 4 =H, R 5 =Q=CH 3 ; the drug precursor of R having the formula R—NH 2 is known as pregabalin;

when in formula (II) W=C and has (S) configuration, m=1 and R 0 if defined as for gabapentin with n=1; R 1 =H; R 2 is the radical of formula (IIA) in which p=p 1 =p 2 =p 3 =0, R 4 =H, R 5 =Q=CH 3 ; the drug precursor of R having the formula R—NH 2 is known as (S)3-isobutilGABA.

4. Compounds according to claim 1 selected from:

1-[4-(nitrooxymethyl)benzoylaminomethyl]-cyclohexaneacetic acid (XVA),

1-[3-(nitrooxymethyl)benzoylaminomethyl]-cyclohexaneacetic acid (XVIA),

1-[2-(nitrooxymethyl)benzoylaminomethyl]-cyclohexaneacetic acid (XVIIA),

1-(4-nitrooxybutanoylaminomethyl)-cyclohexaneacetic acid (XVIIIA),

3-(S)-[4-(nitrooxymethyl)benzoylaminomethyl]-5-methyl-hexanoic acid (XXVA),

3-(S)-[3-(nitrooxymethyl)benzoylaminomethyl]-5-methyl-hexanoic acid (XXVIA),

3(S)-[2-(nitrooxymethyl)benzoylaminomethyl]-5-methyl-hexanoic acid (XXVIIA),

3(S)-[4-(nitrooxybutanoyl)aminomethyl]-5-methyl-hexanoic acid (XXVIIIA),

5. A composition comprising: a compound according to claim 1 ; and a NO-donor compound comprising a radical of a drug selected from the group consisting of: aspirin, salicylic acid, ibuprofen, paracetamol, naproxen, diclofenac and flurbiprofen and at least a group that is an —ONO 2 group or an —ONO group.

6. Pharmaceutical compositions comprising compounds according to claim 1 as active ingredients.

7. A method of treatment of chronic pain comprising administering an effective amount of the compounds according to claim 1 .

8. The method according to claim 7 , wherein the chronic pain is neurophatic pain.