MXPA97009164A - Compounds of heterociclica n-pyridinylenylidenamine, compositions that contain them and using the mis - Google Patents

Abstract

The present invention relates to: A heterocyclic N-pyridinylmethylideneamine compound of the formula (I), wherein R3, A and B are as described below and their pharmaceutically acceptable salts and prodrugs, the compounds of the formula I and its pharmaceutically acceptable salts and prodrugs are useful in the treatment of addictive disorders such as the use of tobacco and other compounds containing nicotine, neurological and mental disorders such as senile dementia of the Alzheimer's type, Parkinson's disease, attention hyperactivity disorder, anxiety , obesity, Tourette syndrome and ulcerative colitis

Description

COMPOUNDS OF N-PYRIDINYLENETHYLIDENAMINE HETERQCICLICR, COMPOSITIONS THAT CONTAIN AND USE THEMSELVES BACKGROUND OF THE INVENTION This invention relates to heterocyclic compounds. Very particularly it refers to N-pip dinilrnet i l -? - l heterocyclic denarnine compounds of the formula T which gives further adelan + e. The compounds of the formula [are useful in the treatment of addictive disorders such as the use of tobacco or other nicotine-containing compounds. These compounds are also useful in the treatment of neurological and mental disorders such as senile dementia of the Alzheimer's type, Parkinson's disease, attention hyperactivity disorder, anxiety, obesity, Tourette's syndrome and ulcerative colitis. Substances that can supply pharmacologically significant amounts of nicotine to the central nervous system are among the known substances that are most abused. These include, but are not limited to, cigars and chewing tobacco (see JE Hennmgfield, Ph.D., Neu. England Journal of Med., 1196, 1995.) Cigarette smoking has been linked to the increased risk to smoking. lung cancer, emphysema and heart disease and it is estimated that 400,000 people will die in 1995 from the combined effects of nicotine abuse in the United States (see JA Califano, Jr., New England Journal of Med. 1214, 1995). A highly addictive drug or with 40% of those who try to smoke later become physical dependents of it.An attempt to stop using nicotine, such as smoking, has been negative with> 80% of such attempts ending in failure Most attempts to quit nicotine fail in the first week due to the intense withdrawal syndrome and desire to use it again.An effective therapy will avoid withdrawal symptoms, alleviate the desire to use nicotine and simulta neously antagonized the nicotine strengthening effects obtained during the time it was used. Currently, some therapies are available for smoking cessation and most involve the replacement of cigarettes with nicotine in par-che or rubber form. A high rate of recidivism and overall success at the end of nicotine use is evidence of the need for additional and more effective therapies for nicotine addition treatment than nicotine patch or gum. The pharmaceutical compositions used for the treatment of chronic nicotinism and nicotine addition can be divided into two groups. The first covers salts of silver, iron and copper. These substances are used to develop a negative reflex for smoking, generally in the form of a solution, or by incorporation in chewing gum compositions. The resulting reflex is based on the appearance of a strong unpleasant taste in the mouth during the turn after a preliminary rinse of the oral cavity in salts solutions, or after the use of a chewing gum - containing said salts (See Nas rov and others "Finabasme Hydrochlorid? -Ne? Antis oking Agent", Chernico-Pharrnaceutical Journal, Vol XII, 1978, No. 2 149-152). The second group of agents used for the suppression of nicotine addiction includes substances of alkaloid natur-aleza, such as citisma, lobeline and anabasine hydrochloride, which have an effect on the H-colino-reactive system of the organism similar to that of the nicotine. The mechanism of its effect is due to its structural similarity to nicotine and the possible "competitive" antagonism between these alkaloids and nicotine (FR Khalikova, SH Nasirov, "Qn pharmacology of the Alkaloid Anabasme and sorne Polimeric and Copoliner c Denvates Thereof" in Coil, "Pharmacology of Vegetable Cornpounds," Proceedmgs of Tashkent U iversity, 457, 1973, 5- d). U.S. Patent No. 4,971,079 discloses a composition comprising a biologically resorbable polymer containing a cation exchange group modified with an alkaloid of antinichotme action, such as anabasine or citisma, and a gum containing the ism. However, it has been found that the potency of cytisine is not high due to its inability to penetrate the brain barrier. (Reav ll, C. et al. .. Behav oural and Pharrnacokinetic Studies Qn Nicotme, Cystune r_nd I obel i ne, Neuroph macoLo, 29, 519-624 (1990)). I abad e L.C. (in Peut-on uppruner les facteurs de risciue in bronchopatie chroru ue et en par-t culier le tabac, Med ater, ined., 1976, 4, No. 112, 97, 99) describes the use of leaves of other nocturnal shade plants, such as potato, tomato, eggplant and dig talis as tobacco substitutes. One of the most successful approaches to date in reducing the incidence of smoking is based on chewing gum that contains no otina that is designed to reduce withdrawal symptoms when you quit smoking. The reported success rate, although still relatively low, is approximately twice that of the other methods that have hitherto been employed (see Bpt sh Medical Journal, 286, (1983)). The use of nicotine gum suffers from several problems including unpleasant taste, destruction of dental appliances and gastrointestinal discomfort thus reducing its use to suppress the addition to nicotine. In addition, it has been found that nicotine-containing gum does not fully satisfy the desire that most smokers experience for nicotine and often nicotine gum makes the patient addictive. A simulated smoker device using a vaporizable nicotine source is claimed in the U.S. Patent. No. 4,284,089. Although the cigar itself is not combustible, it produces a vapor that contains nicotine that may not raise the level of nicotine in the blood enough to satisfy a smoker. In this way, it has not been shown to satisfy the desire for a certain level of nicotine in the blood to which many smokers have become accustomed and even more, from which many smokers have become dependent. Adornas, the simulated smokers devices of the type that are taught in the patent of E.U.A. No. 4,284,089 also suffer from the unpleasant taste of a substantial amount of nicotine introduced into the oral cavity. Very important, this nicotine does not penetrate the chest to stimulate and provide the sensation normally provided by Nicotine and to which the smoker has become accustomed. The first current line of therapy for quitting smoking as described in U.S. Patent No. 5,016,652, describes a transdermal patch that is used for the controlled assortment of nicotine to the user's bloodstream thus reducing the incidence of smoking. . Clinical trials have shown that abstinence rates (with the nicotine patch) of 30 to 40% can be achieved during the first six weeks of application (KJ Palmer, MM Buckley, D. Faulde Drugs 44 (3) 498-529 , (1992), compared with 4 to 21% with a placebo, however, long-term abstinence rates (> 6 months) are considerably lower, falling to 11-18%. effective than a higher percentage of smokers who can quit smoking is clearly necessary.

U.S. Patent Publication UO 92/15564 describes compounds of the formula (R) where Z is defined, inter alia, as p? pd? n-3? optionally substituted and X and Y are as defined herein. The compounds of the formula (R) wherein R2 is hydrogen are useful as intermediates in the preparation of compounds of the formula (R) wherein R2 is not hydrogen. The compounds of the formula (R) wherein R2 is not H are considered useful as insecticides. There is no teaching, nor suggestion, in the reference that the compounds of the formula (R) wherein R2 is H or has the other meanings indicated, can be used in the treatment of addictive disorders such as the use of tobacco or other drugs. -products that contain nicotine or in the treatment of neurological disorders ciméntales. A co-pending application (proxy case No. PC9582), assigned to the assignee of this application and incorporated herein in its entirety, refers to heterocyclic compounds fused with pindin that are useful in the treatment of addictive disorders, such as the use of tobacco or other products that contain nicotine or in the treatment of neurological and mental disorders. the co-pending sole proprietorship (case of proxy No. PC9728), assigned to the transferee of this application and incorporated herein in its entirety refers to 7-aza-b? c? clohe? at us that are useful in the treatment of addictive disorders such as the use of tobacco or other products that contain nicotine or in treatment of neurological and mental disorders.

BRIEF DESCRIPTION OF THE INVENTION The present invention relates to heterocyclic N-pyr-idinylmethylidene aranines of the formula and its pharmaceutically acceptable acid addition salts and prodrugs, wherein A is -CH (R) - and R is hydrogen or optionally substituted Ci-Cß alkyl wherein the substituents comprise one or more individually selected hydroxyl groups, Ci alkoxy -Cß, oxo, C2-C6 alkanoyl and NR * RS; and Jl e < , an < j? upo of the formula J O wherein Y- J is CH2, NH, 0, S, CH2 CH2, CH = CH, N = CH, NH-CH2, 0CH2 or SCH2; the dotted line represents an optional link; 5 Z is C, N, 0 or S; m s L or 2; n is 0, 1 or 2 with the proviso that n is 0 when Z is 0 or S, n is 1 when Z is N and n is 2 when Z is C; each R1 and R2 is independently selected from hydrogen, optionally substituted Ci-Ce alkyl, optionally substituted Ci-Cβ alkoxy and optionally substituted C2-Ce alkanoyl wherein the substituents on the alkyl or alkanoyl groups are selected from hi roxlio, Ci-Cβ alkoxy, oxo, C2-Cß alkanoyl and NR * R5, or R * and R together with the carbon atoms to which they are attached form an optionally substituted six-membered heteroaromatic ring containing at least one heterogeneous atom will be lesson .. or of N, and 0 and Z is C wherein said subst 1aluents are selected from optional Ci-Cβ alkyl substituted or optionally substituted Ci-C alkoxy wherein said substituents are selected from alkyl of Ci-Cg, optionally substituted Ci-C alkoxy and C2-C alkanoyl & optionally substituted or R1 and one of R2 together form a bond with the proviso that R1 and R2 can not form a bond when Z is 0 or S; R3 is halogen or halogen; and R * and R5 or each independently selected from hydrogen and optionally substituted Ci-Cß alkyl wherein said substituents are selected from Ci-Cß alkyl and halogen; with the conditions tje that when -BA is fixed to position 3 of the pinion ring and R is hydrogen already) R3 is 6-chlorine and i) Z is C, the dotted line r-e represents a bond, m and m are both 1, KL Rl and R2 are both hydrogen, so UY is not selected from CH = CH, CH2, NH, CH = N, 0CH2 or SCH2; n) Z is nitrogen, dotted line r-e represents a bond, n is 0 and rn is 1 then R2 is not CF3; or 111) Z is C, the dotted line represents a bond, n and n are both 2, and each of Rl and R2 is hydrogen, then l-Y is not S; or f > ) R3 is hydrogen, 6-bromo or b-fluoro and Z os carbon, the dashed line r-e represents a bond, \ n and n are both 1, Ri and R2 are both hydrogen-ogen, then U-Y is not sulfur. Preferred compounds of formula T are those wherein Z is N, rn is 1 or 2, U-Y is S or CI-I-CH, R3 is halogen or H, R2 is Ci-C alkyl; or halogen, and the dotted line is a link. Other preferred compounds of formula i are those wherein Z is C, R is Ci-Ce alkyl or hydrogen, rn is 1, UY is S or CH = CH, the dotted line is a bond, R1 and R2 are both hydrogen or Ci-Ce alkyl, or the portion of B corresponding to N U I V / \ < R l), < RC > , is selected from The preferred compounds of the formula I are selected from the group consisting of 3- (6-chloro-p? D-n-3-lmethyl) -3H-, 3, 4Ut? Ad? Azole-2-lidenarnine; 5-rnet? L-3-p? R? D? N -3? Lmet? L-3H-t? Azol-2-? L? Denarn? Na; 3- (6-chloro-p? R? Dm-3- lmet? L) -5-rnet l-3H-r 1,3, .3t? Ad? Ozol-2-yl of ain a; 6-chlor-o-? - (6-chloro-pLpd? N-3-? Lrne l) -2H-p? r? daz? n-3- 11 denaini na; 3- (6-chloro-? Pd? N-3- l? Net? L) -3H-benzoth? Azole-2-? L Ldenainma; 3 -? P d? N -3? LrnetLl-3H-Cl, 3, 431? Ad? Azole ~ 2-? L? Denarn? Na; 3-Cl- (6- "Chloro-? R-? D? N-3- l) -et? L 3-3H- t? Azol-2-? L denarnma; 3-Cl- (b-chloro- r-d? n-3-? l) -et 113-3H-U,, 43t? ad? aolol-2-ylnamnam; 3-C1- (6 ~ chlor-o-? p di n -3-? Lmet? L) ~ t? Azol? D? N-2-?? Denarnma; 3 - pipdi n- 3 - 1 lrnet 11 - t azol i di n- 2 - i li denarnína; 5, 7-d? Rnet? Llp? R? D? N-3-? Lrnet? L-3H-ri, 83naft? R? Dm-2- l deno; 6 -. 6-chloro- - p? R? D? N-3-? Lrnet? I-2H-? r? daz? n-3-? l? denarn? na; and 5-rnet? l-3- p? pd? n -3? lrnet? l-3H ~ Cl, 3, 43 t? ad? azole-2? l? denarn na. Unless otherwise indicated, the term "Halogen" as used herein, include fluorine, chlorine, bromine and iodine. Unless otherwise indicated, the term "alkyl", as used herein, may be straight chain, branched or cyclic and may include straight and cyclic portions as well as branched and cyclic portions. The compounds of formula I may have optical centers and therefore may occur in different stereoisomeric configurations. The invention includes all stereoisomers of the compounds of formula I, including mixtures thereof.

The present invention also relates to < -. all the labeled radioactive ores of the compounds of the formula I comprising at least one radioetique preferably selected from 3H, HC and C. These radioactive compounds are useful as a research and diagnostic tool in pharmacokinetic studies. metabolism and in binding tests both in animals and in humans Furthermore, the present invention relates to a pharmaceutical composition for use in reducing the addition to nicotine in a mammal comprising an amount of a compound of the formula I above, or a pharmaceutically acceptable salt or prodrug thereof, elective in the reduction of nicotine addition and a pharmaceutically acceptable carrier, wherein A is CH (R) - and R is hydrogen or optionally substituted Ci-Ce alkyl wherein the substituents comprise one or more individually selected groups of hydroxyl, Ci-Cβ alkoxy, oxo, C2-C alca alkanoyl and NR * RS, and where Y-W is CH2, NH, 0, A CH2CH2, CH = CH, N = CII, NH-CH2, 00112 < CH2; the dotted line represents an optional link; Z is 0, N, 0 or A rn is 1 or 2; n is 0, 1 or 2 with the condition of (th is 0 when Z is 0 or S, n is 1 when Z is N and n is 2 when 7 is Cacada Rl and R2 is independently selected from hydrogen, Ci alkyl -Cβ optionally substituted, Ci-Ce alkoxy optionally substituted and optionally substituted 2-6 alkanoyl wherein the substituents in the alkyl or alkanoyl groups are selected from hydroxyl, Ci-Ce alkoxy, oxo, 2-Ce alkanoyl and NR * Rs, or R1 and R2 together with the carbon atoms to which they are attached form a substituted optionally six-membered straight heteroary ring containing at least one heterogeneous atom selected from N, S and 0 and Z is C wherein said substituents are selected from Ci-C &optionally substituted alkyl or optionally substituted Ci-Ce alkoxy wherein said substituents are selected from Ci-Cß alkyl, optionally substituted Ci-Cß alkoxy and alkanoyl of C2-Cé optionally substituted or R1 and one of R2 together form a bond with the proviso that R * and R2 can not form a bond when Z is 0 or S; R3 is hydrogen or halogen; and RA and RS are each independently selected from hydrogen and optionally substituted O.sub.i-O.sub.oe alkyl wherein said substituents are selected from d-Ce and halogen alkyl. The present invention relates to a composition as described above, wherein the compound of formula I is selected from the group consisting of 3- (6-chloro-p? R? D? Rv-3"ilrnet? L) -3H-ri, 3,43t? Ad? Azole 2-i lidenapu na; 3-p? R? D? N -3-linoethyl-3H-t? Azole -? -? L idenarnine; 3- (6-chloro) -p? r? d? n-3- lrnet? l) -3H-t? azol-2-? l? a? n? na; 3- (6-chloro-p? dm-3-? lrnet? l) -4-ene ti L-3H-t? azoL-2-lidennan; 3- (6-chloro-β-r?-D ?n ~ 3 ~ l lrnet? L) -4-? Net? L-3H-thiazole-2-? Lidenamma; -rnet? L ~ 3-p? R? D? N-3-? Lrnet? I-3H-t? Azol-2-? L? Denarn? Na; 3- (6-chloro-p? R? D? N-3-? Lnet?) -5-? Net? L-3H-Cl, 3, 43t? Ad? Ozol-2-lideneamine; 6-chloro-2"(6 ~ chlor-o ~ ?? r? D? N-3-? Lrnet? I) - 2H-p? R? Daz? N ~ 3 - lidenarní na; 3- (6 ~ chloro-p? r? d? n-3-? lrnet? l) -3H-benzot? azol-2-? l? denarn? na; 3 -? Pd? N -3? Lmet i-3H-Cl, 3, 43t? Ad? Azole-2? L? Denarn? Na; 3- [l- (6-chloro-p? R? D? N -3? L) -et 13- 3 H-lazol-2-? L? Denarn? Na; 3-Cl- (6-chloro-p? Pd? N-3-? L) -et? L -3H-Cl, 3,43t ad? Azole-2-ididearnine; 3-Cl- (6-chloro-p? Pd? N -3? L) -et? L3-t? Aolol? D? N-2-? L? Denarn? Na; 3-p? Pd? N-3-? Lmet? L-t? Azol? D? N-2-? L? Denarna; 5,7-d? Met? L-l-p? R? D? N-3-? Lrnet? I-3H- [l, 83naft? R? D? N-2-? L? Dena; 6-chloro-2-p? Pd? N-3-? Lrnet? L-2H-p? R? dazi n- 3-? lidenarnine; and 5-metí 1 -3-pi r? d? n-3- ilrn? l-3H-T 1, 3, 3 t? ad? azol-2-ididearnine. In another embodiment, the present invention relates to a method for reducing the addition to nicotine in a mammal, which comprises administering to said mammal an amount of a compound of formula 1 or a pharmaceutically acceptable salt or prodrug thereof, effective in reducing the nicotine addiction wherein A is -CH (R) - and R is hydrogen or optionally substituted Ci-Ce alkyl, wherein the substituyent.es comprise one or more individually selected hydroxyl, alkoxy groups of Ci -Ce. oxo, C2-Ce alkanoyl and NR * R *; and B is a group of the formula OR wherein Y-LJ is C, NH, 0, S, CH2CH2, CH = CH, N = CH, NH-CH2, 0CH2 or SCH2; the dotted line represents an optional link; Z is C, N, 0 or S; m s 1 or 2; n is 0, 1 or 2 with the proviso that n is 0 when Z is 0 or S, n is 1 when Z is N and n is 2 when Z is C; each R1 and R2 is independently selected from hydrogen, optionally substituted Ci-Ce alkyl, optionally substituted C?-Ce alkoxy and optionally substituted C2-Ce alkanoyl wherein the subst tuyent.es in the alkyl or alkanoyl groups are selected of hydroxy, C?-C alco alkoxy, oxo, C 2 -C β alkanoyl and NR * R 5, or Rl and R² together with the carbon atoms to which they are attached form an optionally substituted six-membered heteroaromatic ring containing The other heterogeneous atom selected from N, S and 0 and Z is C wherein said substituents are selected from substituted Ci-C-optionally substituted alkyl or optionally substituted Ci-C-alkoxy wherein said substituents are selected from Ci-alkyl. Ce, optionally substituted Ci-C alkoxy and optionally substituted C2-C alkane or R * and one of R2 together form a bond provided that R1 and R2 can not form a bond when Z is O or S; R3 is hydrogen or halogen; and R * and R5 are each independently selected from hydrogen and optionally substituted Ci-Cß alkyl wherein said substituents are selected from Ci-Ce alkyl and halogen. In another aspect of the previous modality, the 10 compound of formula I is selected from the group consisting of 3 ~ (6-chloro-?? r? d? n-3-1 Irnet j 1) -3H-T 1, 3, 43t? ad? azole - 2 -xl dena ina; 3-p? Pd? N-3 -? Lmet l-3H-t? Azol-2-? L denarn? Na; 3- (6-cLoro-?? pd? N-3-lrnet l) -3H-t? Azol-2-? L? Denarnma; 3- (6-chloro-p? R? D? N ~ 3-? Ltr? L) -4-rnet? L -3H-t? Azol-2-lna? N? Na; 3- (6 ~ chloro-pind n-3-il.net j l) -k -rnet? -3H-t? Azol-2-? L idenamine; - . 5-methyl-3-pipdin- 3-? Lrnet? L-3H-t? Azole-2-? L? Denarn? na 3- (6-chloro-p? Ndi n-3-l? Net l) -5-? Net? L-3H-l, 3, 43t idi ozol-2-lidenidenarin; 6-chloro-2- (6-chlor? -o-p? Pd? N -3? Lmet? L) ~ 2 H-p? R? Daz? N-3-yl denarnin; 3- (6-chloro ~ p? R? D? N-3 ~? Lrnet? L) -3H-benzot? Azol-2-? Idenarnin; 3-p? Pd-r.-3-? Lrnet? L ~ 3 H-Cl, 3,43 thiadiazole 2 -li denami na; 3-Cl- (6-chloro-p? Pd? N -3? L) -et? I -3H-t? Azole-2-? Lna? N? Na; 3-Cl- (6-chloro-p? P? N-3-? L) -et? L -3H-Cl, 3,43 t? Ad? Azole-2-ylidenamine; 3 ~ Cl- (6-chloro-p? R? D? N-3 ~? L) -et? L3-t? Aolol-d-2-? Lj denarnin; 3-p? R? D? N-3-? Lnet? L-t? Azol? D? N-2-??? 5, 7-d? Rnet? L-l-p? R? D? N -3? Lrnet? L-3H-Cl, 83naft? R? D? N-2-? L? Dena; 6-chloro-2-p? R? D? N - 3-? Lrnet? L-2H -? R? Daz? N -3? L? Denarn? Na; and 5-rnet? l-3-?? r? d? n-3-? lrnet? l-3H- [l, 3,43t? ad? azol-2-l? denarn? na. Still other aspects of the present invention relate to compounds of the formula I wherein said pharmaceutically acceptable acid addition salts are the acid salts selected from the group consisting of hydrochloric acid, α-t oiuensulphonic acid, pinapcocid, citric acid, acid SUCCLI'ILCO, acid salt dl co, oxic acid, acid bromh dpco, phosphoric acid, etansulic acid, tartaric acid, di-p-toluoyl tart rich acid and inandelic acid. Another embodiment of the present invention relates to a method for treating addictive disorders and neurological or mental disorders in a mammal comprising administering to said mammal an amount of a compound of the formula T effective in the treatment of addictive disorders and neurological or mental disorders wherein A is -CH (R) - and R is hydrogen or optionally substituted Ci-Cß alkyl wherein the substituents comprise one or more groups selected from hydroxyl, Ci-C alkoxy, oxo, alkanoyl C2 ~ Ce and NR * R5; and B is a group of the formula < RL < R2), in dondo Y -U is CH2, NH, 0, S, CH2 CH2, CH = CH, N = CH, NH-CH2, 0CI-l2 or r.0l .2; the dotted line represents an optional link; Z is C, N, 0 or S; rn is 1 or 2; n is 0, 1 or 2 with the proviso that n is 0 when Z is 0 or S, n is 1 when Z is N and n is 2 when Z is C; each R1 and R2 is independently selected from hydrogen, optionally substituted Oi-Cß alkyl, substituted C1-Oß alkoxy optionally alkanoyl, and optionally C 2 -C 4 alkanoyl wherein the substitutes on the alkyl or alkanoyl groups are selected from hydroxy lo, Ci-Ce alkoxy, oxo, C2 -Ce alkanoyl and NR * RS, or R- and R2 together with the carbon atoms to which they are attached form an optionally substituted six-membered heteroaromatic ring containing at least a heterogeneous atom selected from N, S and 0 and Z is C wherein said substituents are selected from optionally substituted Ci-Cβ alkyl or optionally substituted Ci-C alkoxy wherein said substituents are selected from Ci-C alkyl, Ci-optionally substituted alkoxy and optionally substituted C2-C alkanoyl or R- and one of R2 together form a bond provided that R * and R2 can not form a bond when Z is 0 or S; R3 is hydrogen or halogen; and R * and RS are each independently selected from hydrogen and optionally substituted Ci-C alkyl wherein said substituyents are selected from Ci-Cs alkyl and halogen. In accordance with another aspect of the embodiment, the compound of the. or? r is selected from the group consisting of 3- (6-chloro-?? r? d? n -3? lrnetH) -3H-Cl, 3.43 t ad? zol-2-lideneamine; 3-p? Pd n- 3- Ilinet i-3H-t? Azol -2-i lidenamin; 3- (6-chloro-?? r-? D? N -3-lmet? L) -3H-? Azol- 2 ~? L? Denarn? na 3- (6-chloro-p? Pd? N-3-? Lrnet l) -4 ~ rnet? L-3H ~ t lazol -2-? L? Denarn? Na; 3- (6 ~ chloro-p? Pd n-3? Lrnet? I) -4-rnet? L-3H-t? Azole-2? L? Denarn? Na; -rnet? l-3 ~? pd? n-3-? lrnet? l-3H-t? azol-2? l? denarn? na; 3- (6-chloro-p? Pd? N-3 ~? Lnet?) 5-? Net? L-3H-C1, 3, 43t? Ad ozol-2-ylidenarnine; 6 ~ clo? -o-2- (6-chloro-p? Pd? N -3? Lmet? L) -2H-p? R? Daz? N- 3 -íli dena ina; 3- (6-chloro-pen-din-3-ylmethyl) -3H-benzot-azol-2-l Ldenarnma; 3-p? R? dm-3- lrnet? l-3H-Cl, 3, 43t? ad? azole-2-? l? denarn? na; 3-Cl- (6-chloro-p? P d? -3-? L) -et? L3-3H-t? Azol-2-? L? Denarn? Na; 3-Cl- (6-chloro-?? r? D? N-3-? L) -et? L3-3H-Cl, 3,4 t? Ad? Azole ~ 2-lideninanine; 3-Cl ~ (6-chloro-p? Pd? N ~ 3-? L) -eti-13-tlazol and din-2-? Lj denarnina; 3-p? Pd? N-3-? Lrnet? I-t? Azol? D? N ~ 2-? L? Denam? Na; 5,7-d? Rnet? L-l-p? R? D n -3? Lrnet? L ~ 3H- [l, 8 naft? Pd? N-2- l? Dena; 6-chloro-2-p? R? D? N-3-? Lrnet? L ~ 2H - ?? pdaz? N -3? L? Denarn? Na; Y '.' -inet 11-3- pin d n- 3-? Line *? L-3H-Cl, 3, 3t? Ad? Azole-2-ialidenarnine. Another embodiment of the present invention relates to the composition for treating addictive disorders and neurological or mental disorders in a mammal comprising an amount of a compound of formula T effective in the treatment of addictive disorders and neurological or mental disorders. wherein A is -CH (R) - and R is hydrogen or optionally substituted Ci-C alkyl wherein the substituents comprise one or more individually selected hydroxyl groups, Ci-C alkoxy, oxo, C2-C alkanoyl and NR * RS; Y B is a group of the NH formula I U I c where Y-U is CH2, NH, 0, S, CH2CH2, CH = CH, N = CH, NH-CH2, the dotted line represents an optional bond; Z is C, N, 0 or S; m is 1 or 2; n is 1), 1 or 2 with the proviso that n is 0 when Z is 0 or A i is 1 when Z is N and n is 2 when 7 is C; each R1 and R2 is independently selected from hydrogen, optionally substituted Ci-Cß alkyl substituted, optionally substituted Ci-C alkoxy and optionally substituted C2-C alca alkanoyl wherein the substi uyent.es in the alkyl or alkanoyl groups are selected from The hydroxyl, Ci-C alkoxy, oxo, C 2 -Ce alkanoyl and NR * RS, or R 1 and R 2 together with the carbon atoms to which they are attached form an optionally substituted six-membered heteroaromatic ring containing at least minus one heterogeneous atom selected from N, S and 0 and Z is C wherein said substituents are selected from optionally substituted Ci-Ce alkyl or Ci-C alkoxy optionally substituted wherein said substituents are selected from Ci-C alkyl, optionally substituted Ci-C alkoxy and optionally substituted C2-C alkanoyl or R1 and one of R2 together form a bond provided that R- and R2 can not form a bond when Z is 0 or S; R3 is hydrogen or halogen; and R * and RS are each independently selected from hydrogen and optionally substituted Ci-Ce alkyl wherein said substituents are selected from Ci-Cß alkyl and halogen. In accordance with another aspect of the above embodiment, the compound of formula I it is selected from the group consisting of 3 - (6-n-i -o-in dn 1-useful) -3H-Tl, 3, 4lt adol-2-aminoidene; 3- p? R? D? N-3-? Lmet? L-3H-t? zol-2 ~? 1 idena ina; 3- (6-chloro-p? R? D? N-3-? Lmet? L) -3H-tlazol- 2-? L idenarnma; 3- (6-chloro-in-din-3- lmet-11) -? - rnet? L-3H-t azol-2-l? Denam? Na; 3 ~ (6-chloro-p? R? D? N ~ 3- lrnet? L) -4 ~ rnet? L ~ 3H-t? Azol-2- l. Der.arn? Na; - . 5-metí 1 -3-p? Pd? N-3- lme l-3H-t azol-2-l? Denarn? Na; 3- (6-chloro-η-d-n-3-γ-methyl) -5-methyl-3H- [1, 3,43t? Ad? Ozol-2-ialidenarnma; 6-chloro-2 ~ (6-chloro-β-pd? N-3-lrnet? L) -2H-p? R? Dazm-3-lidenami na; 3- (6-chloro ~ p r? D? N -3? Lmet l) -3H-benzot? Azole-2-? Ldenarn? Na; 3-? pd? n-3? lrnet? l-3H- [1, 3, 43t? ad? azole-2-? l? denarn? na; 3-Cl- (6-chloro-p? R? D? N -3? L) -et? L -3H-t? Azole-2-? L? Denarn? Na; 3-Cl- (6-chloro-p? Pd? N-3-? L) -et? L -3H-C 1, 3, 43? Ad? Azole-2-ididearnine; 3-Cl- (6-chloro-p? R? D? N-3-? L) -et? I3-t? Aolol-d-2? -lan? N? Na; 3 -? Pd? N -3? Lmet? I-t? Azol? D? N-2-? L? Denarna; 5,7-d? Rnet? L-l-p? Pd? N -3? Lrnet? L-3H-Cl, 83naft? R? D? N-2-? L? Dena; 6-chloro-2-?? pd? N -3? Lrnet? L-2H-?? r? Daz? N -3? L? Denarn? Na; and 5-rnet? l-3-p? pd? n-3? lrnet? l-3H- [l, 3,43t? ad? azole-2? l? denarn? na. Examples of pharmaceutically acceptable acid addition salts of the compounds of the formula I are the salts of hydrochloric acid, p-toluenesulfonic acid, fumaric acid, citric acid, succinic acid, salicylic acid, oxic acid, brornhydric acid. , phosphoric acid, methansulonic acid, tart-rich acid, di-p-tol-uoiltartapco acid and ico-manic acid.

DETAILED DESCRIPTION OF THE INVENTION In the following schemes and discussion R, R1, R2, R3, R *, RS, A, B, X, U-Y, Z, rn and n have the meanings given above.

), III I (R3 = halogen) dehalogenation 1 (R3 = hydrogen) Fn each of the reactions discussed below, or illustrated in the previous scheme, the pressure is not critical unless indicated otherwise. Generally pressures of about 0.5 atmospheres to about 5 atmospheres are acceptable, with environmental pressure being preferred for convenience, approximately 1 atmospher-a. As shown in the scheme, compound T is prepared by reacting compound TT, wherein X is a leaving group which can be displaced by an arnide group, with the compound of formula ITT. The outgoing grupts are well known in the art and include rnesylate, tosylate, tnflato, acetate and halogen. The outgoing group I intend is halogen. The reaction is usually carried out in an inert solvent such as a ketone, for example, acetone or a C?-Ce alcohol, such as ethanol, in the optional presence of an added base, at a temperature of about room temperature. at the reflux temperature of the solvent or mixture of solvents in the presence of a base. The reaction is preferably carried out in acetone or ethanol at the reflux temperature of the solvent. The bases which are useful in the above reaction include excess amounts of the reactants or products, or are selected from carbonates, bicarbonates and alkali metal hydroxide, and organic amines such as TEA, and the like. Generally, the reaction is performed in the absence of added bases. If X is not iodine in compound II, then the reaction can also be carried out in the presence of catalytic amounts or in molar excess - (relative to the pyro-linet ilchlor group) of iodide ions. The iodide ions can be provided in the form of alkali metal iodide, such as Nal and Ki, and in the form of organic base hydroiodides such as t-ethyl amide hydroiodide. Although iodide ions are not essential to effect the reaction, they are thought to affect the reaction, for specific reagents, by converting the alkyl chlorides to their correct iodides which are more easily ammoniated, ie , the speed of fusion has increased with the presence of iodide ions and the speed is proportional to the concentration of iodide ion. Preferably, the iodide ions are used in excess amounts. The compounds of formula II are commercially available or can be prepared by methods known in the art (See v.gr-., 3 Het. Chern., 1979, ib, 333-36). The compounds of formula III are commercially available. The compounds of formula I, wherein R 3 is a halogen atom, can be dehalogenated to form compounds of formula I wherein R 3 is hydrogen by treatment with hydrogen in the presence of a hydrogenation catalyst such as Pd on carbon, Pd (0H) 2 , Pd / C and Raney nickel, and the like. The reaction is generally carried out in an inert solvent, such as a Ci-C alcohol, for example rnetanol, at an H 2 pressure of about atmospheric at about 345 I Pa at a temperature from about room temperature to the reflux temperature. of the solvent. Preferred, the reaction is carried out in methanol at room temperature, using Pd / C and an H2 pressure of about 3.5 lPa. Alternatively, dehalogenation can be effected by treatment with a reducing agent such as L1AIH4 and (n ~ but? I) 3 SnH, and mixtures of L1RIH4 and AICI3. Preferably the dehalogenation is effected by treatment with hydrogen in the presence of a hydrogenation catalyst. The salts of the compound of formula I are prepared by treating the free base forms thereof with appropriate acids under the general conditions known in the art. For example, they can be prepared by contacting the compound (group) of the formula I with an appropriate acid, usually in a rich stoichiome ratio in an aqueous, non-aqueous, or aqueous medium, as appropriate. The salts are recovered by filtration, by precipitation with a non-solvent followed by filtration or by evaporation of the solvent, as appropriate, or in the case of aqueous solutions, by means of lyophilization. The typical salts that can be prepared are those of hydrochloric acid, p-toluenesulfonic acid, furnaric acid, citric acid, succinic acid, salicylic acid, oxalic acid, brornhydric acid, phosphoric acid, nitrate sulphonic acid, tartaric acid, di-p-toluyltartan , and nandelic acid. The compounds of formula I and their pharmaceutically acceptable salts (hereinafter "the active compounds") can be administered by any of the oral routes, transdermal (for example, by using a patch), m-nasal, sublingual, rectal, parenteral or topical. T ransderrnic and oral admi ss is preferred. Most conveniently, these compounds are administered in dosages ranging from about 0.25 rng to about 1500 rng per day, preferably from about 0.25 to about 300 rng per day in single or divided doses, although variations necessarily occur depending on the subject's weight and condition. treat and the particular route of administration chosen. However, a dosage level on the scale of about 0.02 mg to about 10 mg per l >is very conveniently employed.-g of body weight per day. However, variations may occur depending on the weight and condition of the persons to be treated and their individual responses to said medicament, as well as on the type of pharmaceutical formulation chosen and the period and interval during which said administration is carried out. In some cases, dosage levels below the lower limit of the scale mentioned above may be more than adequate, while in other cases even higher doses may be used without causing any harmful side effects, provided that these larger doses are divided first. in several small doses for administration throughout the day.

The . Active compounds can be administered alone or in combination with pharmaceutically acceptable carriers or diluents by any of the different routes indicated above. Most particularly, the active compounds can be administered in a wide variety of different dosage forms, for example they can be combined with different pharmaceutically acceptable inert carriers in the form of tablets, capsules, tranederrn pairs, lozenges, troches, hard candies, powders , aerosols, creams, plasters, suppositories, jellies, gels, pastes, lotions, ointments, aqueous suspensions, injectable solutions, elixirs, syrups and the like. These vehicles include diluents or solid fillers, sterile aqueous media and different non-toxic organic solvents. In addition, the oral pharmaceutical compositions can be sweetened and / or flavored properly. In general, the active compounds are present in these dosage forms at concentration levels ranging from about 5.0% to about 70% by weight. For oral administration, tablets containing different excipients such as cornstarch-cellulose, sodium citrate, sodium carbonate, dicalcium phosphate and glycine can be used together with different disintegrants such as starch (preferably corn starch, potato or tapioca), alginic acid, and certain complex silicates, together with granulation binders such as polyvinylpyrrolidone, sucrose, gelatin and acacia.

Additionally, lubricating agents such as magnesium stearate, sodium latent and such or for tableting purposes can be used. Solid compositions of a similar type can also be used as fillings in gelatin capsules; the preferred materials in this regard also include lactose or milk sugar, as well as high molecular weight polyethylene glycols. When aqueous suspensions and / or elixirs are desired for oral administration, the active ingredient may be combined with different sweetening or flavoring agents, colorants, and, if convenient, ernulifying and / or suspending agents together with diluents such as water, ethanol, propylene glycol, glycerin and different combinations thereof. For parenteral administration, a solution of an active compound in sesame or peanut oil or in aqueous propylene glycol can be employed. If necessary, the aqueous solutions must be properly regulated in their pH, and first the liquid diluent becomes isotonic. These aqueous solutions are suitable for intravenous injection purposes. Oily solutions are suitable for intra-articular, intramuscular and subcutaneous injection purposes. The preparation of all these solutions under sterile conditions is easily effected by standard pharmaceutical techniques well known to those skilled in the art. It is also possible to administer the active compounds only when inflammatory conditions of the skin are treated, and this can be done by means of creams, jellies, gels, pastes, ointments and illary, in accordance with normal pharmaceutical practice.

Biological test The effectiveness of the active compounds in the suppression of nictone binding to specific receptor sites was determined by the following procedure, which is a modification of the methods of Lippiello, PM and Fernandos, KG (in The Bindmg of L-- __ H3N? Cot? Ne To A Single Class of High-Affinity Sites in Rat Bram Mernbranes, Molecular Pharm., 29, 448-54, (1986)) and Anderson, D.7. and Arneric, S.P. (in Nicotinic Receptor Bmding of H-Cyst? s? ne, H-N? cot? ne and 3H-Methylcarrnbarnylchol ine In Rat Brain, European 3. Pharm., 253, 261-67 (1994)).

Procedure Groups of Sprague-Dawley rats (200-300 g) from Charles River were housed in stainless steel wire hanging cages and maintained in a 12-hour cycle of light / dark (light period 7 a.rn.- 7 pm). They received Purina Rat Chow normal and water ad libiturn. The rats were euthanized by decapitation. The brains were removed immediately after decapitation. Brain tissue membranes were prepared, according to the methods of L ppiello and Fernandez (Molec Phn ncol, 29, 448-454, (1986), with some modifications, whole brains were removed, rinsed with pH-regulator. cooled with ice and ovenified at 0 ° C in 10 volumes of pH regulator (w / v) using a Bpn mann Polytron ™ fi x 6, for 30 seconds.The pH regulator consisted of 50 mM Tris HCl and had a pH of 7.5 at room temperature The ovenified product was sedimented by centrifugation (10 minutes 50,000 xg, 0 to 4 ° C) The supernatant was separated by decanting and the membranes were gently resuspended with the Polytron and centrifuged again (10 minutes, 50,000 xg, - 0 to 4 ° C.) After the second centrifugation, the membranes were resuspended in the test pH buffer at a concentration of 1 μg / 100 rnl. pattern was 50 rnM Tris HCl, 120 rnM N aCl, 5 rnM KCl, 2 rnM MgCl, 2 rnM CaCl2 and had a pH of 7.4 at room temperature. Routine tests were carried out on borosilicate glass test tubes. The test mixture typically consisted of 0.9 ng of membrane protein in a final incubation volume of 1.0 rnl. 3 groups of tubes were prepared; the tubes in each group contained 50μl of vehicle, blank, or test compound solution, respectively. To each tube was added 200 μl of C3H3-n? Cotma in regulator-pH test followed by 750 μl of the membrane suspension. The final concentration of nicotine in each tube was 0.9 nM. The final concentration of citisma in the blank was 1 μM. The vehicle consisted of water desized with 30 μl of 1 N acetic acid per 50 ml of water. The test compounds and the cytisine were each dissolved in a vehicle. The tests were started by mixing with vortex formation after the addition of the membrane suspension to the tube. The samples were incubated at 0-4 ° C in a water bath stirred with ice. Incubations were terminated by rapid vacuum filtration through lhatrnan GF / BTM glass fiber filters using a BrandelTM multiple tissue harvester "After initial filtration of the test mixture, the filters were washed twice with pH buffer of test cooled with ice (5 ml each). The filters were then placed in counting jars and mixed vigorously with 20 rnl of Ready Safe ™ (Beclrnan) before quantification of radioactivity. Samples were counted in a liquid scintillation counter LKB Uallach RackbetatM efficiency of 40-50%. All determinations were in triplicate.

Calculations The specific binding IX to the membrane is the difference between the total binding in the samples containing vehicle only and the VIT membrane, and the binding does not specify in the samples containing the membrane and cytisine VIII, ie, Specific binding = IX = VII - VIII The specific binding in preemption of the test compound XT is the difference between the total binding in the presence of the compound (Je test X and the non-specific binding VIII, ie-, XT - X - VITI.% Inhibition = (1-XI / IX) times 100. The compounds of the invention that were analyzed exhibited CIso values of less than 2 μM.

EXAMPLE 1 N- (6-Chloro-p? Rid n-3-ylmethyl) -3H- [lJ3J4] t? Adiazole-2-ylidenamine A. N-chloromethyl-6-chloropyridine (717 mg, (4.43 inM)) was mixed (prepared according to the method of 3. Het Chem., 1979, 16, 333- 336), 537 rng (5.31 rnM) of 2-aminol-l, 4-thiadiazole, and 1.99 g (13.29 inM) of sodium iodide together in 60 rnl of acetone and refluxed for 18 hours. The reaction mixture was cooled to room temperature and the solvent was evaporated. The residue was dissolved in a 1: 1 mixture of 50 rnl of 10% NaOH and 50 rnl of methylene chloride. The organic layer was dried (Na 2 SO 3) and the solvent was evaporated. The residue was subjected to chromatography on silica using 2% rnetanol in rnetienene chloride as eluent. The appropriate fractions were combined to yield 282 mg (28%) of the title compound as an oil. RMN-iH (CDC13) or 8.45, (d, 1H, 3 = 2.8 Hz), 7.70 (dd, 1H, 3 = 2.8, 10.7 Hz), 7.60 (s, 1H, 3 = 10.7 Hz), 7.28 (d, 1H, 3 = 10.7 Hz ), 5.10 (s, 2H). B. The oil from part A was dissolved in ethyl acetate and treated with gaseous HCl. A solid precipitate formed. The solvent was evaporated and the residue dried under high vacuum to yield 256 mg of the hydrochloride salt of the title compound as a white-colored amorphous solid. NMR- * 3C (DMSO-de) & 167.1, 150.3, 149.9 145.8, 140.1, 129.5, 124.5, 49. 9 Mass spectrum: rn / e =? 2, 229.

EXAMPLES 2-13 The title compounds of Examples 2-13 were prepared according to the method of Example IA.

EXAMPLE 2 N- (Pyridin-3-lmethyl) -3H-thiazole-2-ylidenamine NMR-iH (CDC13) or 8.5 (rn, 2H), Jn (rn, 1H), 7.2 (m, 1H), 6 .. (d, 1H, 3 = 8.5 Hz), 5.2 (d, 1H, JB. 5 Hz), 4.90 (s, 1H). NMR-13C (CDCl3) d 164.4, 149.2, 149.0, 135.5, 132.3, 126.6, 123.7, 98.7, 46.5. Mass spectrum:? N / e = 192 (p + 1).

EXAMPLE 3 N- (6-Chloro-pyridin-3-ylmethyl) -4-methyl-3H-thiazole-2-ylidenamine NMR-1H (CDCl 3) d 8.22 (d, 1H, J = 4 Hz), 7.56 (dd, 1H, 3 = 4, 8.2 Hz), 7.22 (d, 1H, 3 = 8.2 Hz), 5.42 (s, 1H ), 4.88 (s, 2H), 1.80 (s, 3H). 13 C-NMR (CDCl 3) d 165.7, 150.5, 148.1, 18 137. 7, 134.2, 131.0, 124..4, 93.6, 43.3, 14.9. Spectrum of ina s s: m / e - 2 0, 4.

EXAMPLE 4 N- (6-Chloro-pyridin-3-ylmethyl) -4-methyl-3H-thiazole-2-ylidenamine NMR-IH (CDC13) d 8.18 (d, 1H, 3 = 4 Hz), 7.55 (dd, 1H, 3 = 4, 8.2 Hz), 7.15 (d, 1H, 3 = 8.2 Hz), 6.20 (br s, 1H). 6.0 (s, 1H), 4.72 (s, 3H), 1.82 (s, 3H). NMR-13C (CDCl3) d 164.6, 150.6, 148.8, 138.5, 131.7, 124.3, 121.9, 111.5, 45.4, 13.1.

Mass spectrum: rn / e = 240.242.

EXAMPLE 5 5-Methyl-N- (pyridin-3-ylmethyl) -3H-thiazole-2-ylidenamine I-NMR (CDCl 3) 8.52 (rn, 2H), 7.69 (rn, 1H), 7.25 (rn, 1H), 6.16 (s, 1H), 5.05 (d, 2H), 2.0 (s, 3H). NMR- * 3C (CDCl 3) d 166.0, 149.4, 149.0, 135.8, 131.5, 123.8, 122.7, 47.3, 12.9. Mass spectrum: rn / e = 206 (p + 1).

EXAMPLE 6 N- (6-Chloro-pyrridin-3-ylmethyl) -5-methyl-3H-1, 3, 4] thiazole-2-ylidenamine 1H-NMR (CDCl 3) 6 8.28 (d, 1H, 3 = 4 Hz), 7.55 (dd, 1H, 3 = 4, 8.2 Hz), 7.16 (d, 1H, 3 = 8.2 Hz), 6.25 (br S, 1H), 4.92 (s, 2H), 2.12 (s, 3H) "RMN-l3C (CDCI3) 6 162.8 , 150.6, 149.4, 140.1, 144.3, 138.9, 137.5, 131.4, 124.1, 123.9, 47. 2, 17.0. Mass spectrum:? N / o- 2 1.24.

EXAMPLE 7 6-Chloro-N- (6-chloro-pyridin-3-ylmethyl) -2H-pyridazin-3-ylidenamine NMR-lH (CDCl 3) d 0.35 (d, 1H, 3 = 4 H), 7.68 (dd, 1H, 3 = 4, 8.2 Hz), 7.16 (d, 1H), 3 = 8.2 Hz), 6.60 (d, 1H, 3 = 12.75 Hz), 6.52 (d, 1H, 3 = 12.75 Hz), 5.70 (br s, 1H), 5.05 (s, 2H).

C-NMR (CDCl 3) d 154.9, 150.7, 149.9, 139.2, 134.8, 132.4, 130. 7, 128.1, 124.0, 52.4. Mass spectrum: rn / e = 255, 257.

EXAMPLE 8 N- (6-Chloro-pyridin-3-ylmethyl) -3H-benzothiazol-2-ylidenamine NMR-1H (CDCl 3) d 8.37 (rn, 1H), 7.62 (m, 1H), 7.25 (m, 2H), 7.12 (rn, 1H), 6.95 (rn, 1H), 6.72 (rn, 1H), 5.12 (s, 2H). 13 C-NMR (CDCl 3) d 161.9, 150.7, 148.6, 139.7, 138.0, 130.8, 126. 4, 124.2, 122.6, 122.3, 122.0, 109.4, 43.0. Mass spectrum: m / e = 276, 278.

EXAMPLE 9 N-Pyridin-3-yl ethyl-3H-Cl, 3,4] thiadiazol-2-ylidenamine NMR-1H (CDCl 3) d 8.62 (S, 1H), 8.50 (M, 1H),? .68 (M, 1H), 7.55 (S. 1H), 7.22 (M, 1H), 5.09 (D, 2H) . 13 C-NMR (CDCl 3) 6 161.1, 149. ?, 149.2, 135.9, 133.0, 132.0, 123.4, 48.4. Mass spectrum: rn / e = 193 (P + l).

EXAMPLE 10 N- [1- (6-Chloro-pyridin-3-yl) -ethyl-3-H-thiazole-2-ylidenamine NMR-1H (CDCl 3) d 8.7 (s, 1H), 7.55 (d, 1H, 3 = 8.2 Hz), 7. 25 (d, 1H, 3 = 8.2 Hz), 6.41 (d, 3 = 3 Hz), 5.90 (d, 3 = 3 Hz), 5.72 (q, 1H), 1.65 (el, 3H).) 13 C-NMR (CDCl 3) d 164.5, 150.8, 148.0, 137.5, 135.4, 124.3, 123.4, 99.9, 50.6, 19.4. Mass spectrum: rn / e = 239, 241.

EXAMPLE 11 N-Cl- (6-Chloro-pyridin-3-yl) -ethyl] -3H- [lJ3,4] thiadiazol-2-ylidenamine NMR-1H (CDCl 3) d 8.35 (s, 1H), 7.52 (d, 1H, J = 8Hz), 7.51 (s, 1H), 7.25 (d, 3 = 8 Hz), 5.43 (q, 1H), 1.70 (d, 3H). NMR-lSC (CDCl 3) d 160; 9,150.6. 148.7, 137.6, 135.6, 132.9, 124.0, 52.1, 19.7. Mass spectrum: rn / e = 240, 242.

EXAMPLE 12 N-Cl- (6-Chloro-p? R? Din-3-ylmethyl) -thiazolid? N-2-yl? Deamine NMR-lH (CDC13) d 8.15 (s, 1 H), 7.55 (d, 1H, 3 = 8Hz), 7.16 (d, 1H, 3 = 8Hz, 6.15 (hr s, 1H), 4.45 (s, 2H) , 3.40 (t, 2H), 3. 05 (t, 2H). NMR-1SC (CDCl 3) d 164.3, 150.4, 149.0, 138.8, 131.8, 124.2, 51.2, .6.0, 26.9. Mass spectrum:? N / e = 220, 230.

EXAMPLE 13 N- (Pir? Din-3-ylmethyl) -t? Azolidin-2-ylidenamine RMN-lH (CDCl3) d 8.45 (rn, 2H), 7.65 (m, 1H), 7.22 (n, 1H), 5.05 (br s, 1H), 4.55 (s, 2H), 3.44 (t, 2H), 3.07 (t, 2H). NMR-1SC (CDCl 3) d 164.6, 149.3, 148.9, 135.8, 132.7, 123.6, 51.2, 46.8, 26.9. Mass spectrum: rn / e = 194 (p + 1).

EXAMPLE 14 5 J7-Dimethyl-N- (pyrid? N-3-yl ethyl) -3H- [l, 8] naphthyridin-2-ylidene A mixture of 1.27 g (0.01 rn) of 3-chlorornet? Lp? R? D? Na and 1.43 g (0.083 rn) of 7-ammo-2, 4-d? Rnet? L- was refluxed. -naft? pd in 15 ml of ethanol for 16 hours. The reaction mixture was cooled to room temperature and filtered. The solvent was evaporated and the residue was subjected to chromatography on 150 rng of silica using 10: 1 CHCl 3: methanol as eluent. The appropriate fractions were combined and the solvent evaporated. The residue was recpetalized from alcohol and so obtained 1 LCO to produce 60 mg of the free base form of the title product. P. r. 256-259 °. NMR-lH (DMSO-dβ) d 8.6 (, 1H), 0.5 (m,? H), 7.6 (d, 1H), 7.4 (s, 1H), 7.35 (rn, 1H), 7.29 (d, 1H) , 5.95 (s, 2H), 2.53 (s, 3H), 2.53 (s, 3H). Mass spectrum: m / e-265.2 (p + 1).

EXAMPLE 15 6-Chloro-N- (pyridin-3-ylmethyl) -2H-pyridazin-3-ylidene ina This compound was prepared according to the method of example 14. Mass spectrum: rn / e = 221/223.

EXAMPLE 16 5-Methyl-N- (pyridin-3-ylmethyl) -3H-ClJ3 4] thiadiazole-2-ylidenamine A. To a solution of 100 mg (0.32 nm) of the hydrochloride salt of the product of the title of Example B, in 100 mL of methanol, 200 mg of 10% Pd / C was added. This mixture is hydrogenated at 345 Kpa for 12 hours. The reaction mixture was filtered and the solvent was removed from the filtrate by evaporation. The residue was dissolved in 25 mL of ethyl acetate and washed with saturated sodium bicarbonate. The organic layer was dried (Na2SO) and the solvent was evaporated to yield 50 mg of the title product as an amorphous solid. NMR-1H (DMSO-dβ) d 8.62 (rn, 1H), 8.50 (m, 1H), 7.68 (m, 1H), 7.20 (rn, 1H), 5.02 (s, 2H), 2.20 (e, 3H) , 13 C-NMR (CDCl 3) d 163.2, 149.5, 149.0, 135.8, 132.3, 123.4, 48.1, 17 .. ü. Hand spectrum: \ i] / e = 2ü / (? +1). The compound of Example 17 was prepared according to the method of Example 16.

EXAMPLE 17 5.7-Di ethyl-l (6-chloro-pyridin-3-yl ethyl) -lH-Cl, 8] n tiridin-2-ylidenamine Base: RMN-lH (DMSO-dβ) d 9.5 (br, s 1H), 8.53 (d, 1H), 8.40 (s, 1H), 7.67 (d, 1H), 7.50 (d, 1H), 7.40 (s, 1H), 7.20 (d, 1H), 5.90 (s, 2H), 2.62 (s, 3H) ), 2.55 (s, 3H). Mass spectrum: rn / e- ~ 299, 301 (P, P + 2).

EXAMPLE 18 3-Pyridin-2-ylmethyl-3H-Cl, 3,4] thiadiazol-2-ylidenamine hydrochloride A mixture of 2-chlorornet? Lpyr? Dna (1.75 g, 0.0137 M) and 2-a? N? No-l, 3,4-thiadiazole (1.09 g, 0.0108 M) was refluxed for 20 hours at 20 rnl of ethyl alcohol. The reaction mixture was cooled to room temperature and filtered. The precipitate was washed with ethyl acetate and dried to yield 0.680 g of the title compound. P. f, = 187-189 ° C NMR-lH (DMSO-de) d 10.6 (br s, 1H), 9.0 (s, 1H), 8.5 (d, 1H), 7. 9 (rn, 1H), 7.48 (d, 1H), 7.38 (m, 1H), 5.7 (s, 2H). NMR-13C (DMSO-de) d 167..7, 153.0, 149.3, 145.0, 137.4, 123.4, 122.4, 54.0. Mass spectrum: rn / e = 193 (? +1).

Claims (14)

NOVELTY OF THE INVENTION
2. N-p mdi and heterocyclic limetilidenarninas of the fo-mule and its pharmaceutically acceptable acid addition and pharmaceutical salts, wherein A is -CH (R) - and R is hydrogen or optionally substituted Ci-Cß alkyl wherein the substituents comprise one or more individually selected hydroxyl groups, Ci alkoxy -Ce, oxo, C2 -Ce alkanoyl and NR * RS; and B is a group of the formula where Y-) is CH2, NH, O, S, Ct-bC ^, CH = CH, N = CH, NH-Chb, 0CH or SCH; the dotted line represents an optional link; Z is C, N, 0 or S; rn is 1 or 2; n is 0, i or 2 with the proviso that n is 0 when 7 is 0 or S, n is 1 when Z is N and n is 2 when Z is C; Each R1 and R2 is independently selected from hydrogen, optionally substituted Ci-Cß alkyl, optionally substituted Ci-Cß alkoxy, and optionally substituted C 2 -C alk alkanoyl wherein the substituents on the alkyl or alkanoyl groups are selected from hydroxyl, alkoxy, C? ~ Cß, oxo, C -Ce alkanoyl and NR * R5, or R1 and R2 together with the carbon atoms to which they are attached form an optionally substituted six-membered heteroaromatic ring containing at least a heterogeneous atom selected from N, S and O and Z is C wherein said substituents are selected from optionally substituted Ci-Cβ alkyl or optionally substituted Ci-Ce alkoxy wherein said substituents are selected from Ci-Cβ alkyl optionally substituted Ci-C alkoxy and optionally substituted C-C alkanoyl or R 1 and one of R 2 together form a bond with the proviso that R and R 2 can not form a bond when Z is O or S; R3 is hydrogen or halogen; and R * and Rd are each independently selected from hydrogen and optionally substituted Ci-Cß alkyl wherein said substituents are selected from Ci-Ce alkyl and halogen; with the conditions that when -BA is fixed to position 3 of the pyridine ring and R is hydrogen already) R3 is 6-chlorine and i) Z is C, the dotted line represents a bond, rn and n are both 1, KL Rl and R2 are both hydrogen, then UY is not selected from CH-CH, S, CH2, MH, Cl-I-N, 0CH2 or SCH2; 11) Z is nitrogen, the dotted line represents a bond, n is 0 and rn is 1 then R2 is not CF3; or 111) Z is C, the dotted line represents a bond, rn and n are both?, and each of Rl and R2 is hydrogen, so U-Y is not S; or b) R3 is hydrogen, 6-bromo or 6-fluor and Z is carbon, the dotted line represents a bond, m and n are both 1, Rl and R2 are both hydrogen, then U-Y is not sulfur. 2. The compound according to claim 1, further characterized in that Z is N, rn is 1 or 2, UY is S or CH = CH, R3 is halogen or H, R2 is Ci-Ce alkyl or halogen, and the dotted line is a link.
3. 3. The compound according to claim 1, further characterized by the fact that Z is C, R is Ci-Ce alkyl or hydrogen, m is 1, UY is S or CH = CH, the dotted line is a bond , R1 and R2 are both hydrogen or Ci-C3 alkyl, or the portion of B corresponding to N IV \ (R1), (R¿) (is selected from
4. 4. - The compound according to claim 1, further characterized in that it is selected from the group comprising 3- (6-chloro-p? Pd? N -3? Lmet? L) -3H-C1, 3, 43t? Ad? azol-2-ylna denamine; 5-metii-3-p? R? D? N -3? Lmet? I-3H-t? Azol-2-ididearnm; 3- (6-chloro-?? r? D? N -3? Lmet? I) -5-rnet? L-3H-r 1,3,4] t? d? ozol-2-? l Ldenarnin; 6-c IOG? 2- (6-chloro ~? L ri din- -Llrnet L1) -2H - ?? -? da? n-3-? 1 of ainma; 3- (6-chloro-? P in-'l line i 1) - 3 H -benzot? Azole-2- Llidenarni a; 3-? Pd? N-3- Llrneti l -3H-n, 3, 4lt? Ad? Azole - 2-? lidenarnine; 3- Ti- (6-eloro ~ p? Pd? N -3? L) -et? L] -3H-t? A ol-2-? L? Denarn? Na; 3-Cl- (6-clsro-? P di n ~ 3 ~? L) -et? L] ~ 3 H ~ Cl, 3, 4] t? Ad? Aolol-2-ylidenami na; 3-C 1 - (5-chloro-pen-di-3-lrnet? L) -thiazole d? N-2-? L? Denam? Na; 3-p? Pd? N-3-? Lnet? L-thiazolidin-2-? L? Denarn? Na; 5, 7-d? Rnet? 1-1-p? Pd? N- 3 ~? lrnet? l ~ 3H ~ Cl, 8] naft pd? n-2-? l? deno; 6 -clo o- 2 -pin din- 3 -? Irnet? L ~ 2H ~ ?? r? Daz? N -3? L? Denarna; and 5 - met? l-3 - ?? r? d? n-3 ~ i lmet? ~ 3H ~ Cl, 3, 4lt? Ad? Azol -2- ildendenine.
5. 5. The compound according to claim 1, further characterized in that it comprises racenatos, stereoisomers and mixtures thereof.
6. 6.- The compound of opnidad with the reividication 1, further characterized in that it comprises at least one selected radioet of 3H, nc and? * C.
7. 7. The compound according to claim 6, further characterized in that said radiolabel is 3H.
8. 8. The compound in accordance with the claim 6, further characterized by the fact that said radiolabel is nc.
9. 9. The compound according to claim 6, further characterized in that said radiolabel is? C.
10. 10. A pharmaceutical composition for use in reducing nicotine addiction in a mammal comprising an amount of a compound of formula I above, or a pharmaceutically acceptable salt or prodrug thereof, effective in the treatment of addiction. to nicotine and a pharmaceutically acceptable carrier, wherein fl is CH (R) - and R is hydrogen or optionally substituted Ci-C alkyl wherein the substituyents comprise one or more individually selected hydroxyl groups, O-alkoxy -Ce, oxo, C2 -Ce alkanoyl and NR * RS, and B is a group of the formula where Y-U is CH2, NH, 0, S, CFb CH2, CH = CH, N = CH, NH-CH? , 0CH2 or SCH2; the dotted line represents an optional link; Z is C, N, 0 or S; rn is 1 or 2; n is 0, 1 or 2 with the proviso that n is 0 when Z is 0 or S, n is 1 when Z is N and n is 2 when Z is C; each R 1 and R 2 is independently selected from hydrogen, optionally substituted Ci-Cβ alkyl, optionally substituted Ci-Cβ alkoxy and optionally substituted C 2 -C β alkanoyl wherein the substituents on the alkyl or alkanoyl groups are selected from hydroxy, alkoxy Ci-Ce, oxo, C2-Ce alkanoyl, and NR * R5, or R and R2 together with the carbon atoms to which they are attached form a heteroaryl ring of STLS members optionally substituted with at least one atom heterogeneous selected from N, S and 0 and Z is C wherein said substituents are selected from optionally substituted Ci-C alkyl or optionally substituted Ci-C alkoxy wherein said substituents are selected from Ci-C-alkoxy, Ci -Ce optionally substituted and optionally substituted C 2 -C β alkanoyl or R 1 and one of R 2 together form an enyl with the proviso that R 1 and R 2 can not form a bond when Z is 0 or S; R3 is hydrogen or halogen; and R * and R5 are each independently selected from hydrogen and optionally substituted Ci-Ce alkyl wherein said substituents are selected from Ci-Cß alkyl and halogen.
11. 11. The composition according to claim 10, further characterized in that the compound of the formula I is selected from the group consisting of 3- (6-chloro-p? Pdm-3? Lrnet? L) -3H-C1 , 3, 4] t? Ad? Azol-2??? Denarn? Na; 3-p? R? D? N-3-? Lrnet? L-3H ~ t? Azol ~ 2-? L? Denarn? na 3- (6-chloro-?? r? D? N-3-? Lrnet? L) -3H-t? Azol-2? L? Denarn? Na; 3- (6-chloro-β-pd-n-3-yl-ineyl) -4-rnet-l-3H-t-azole-2-γ-ionene; 3- (5-chloro-β-pd? N-3-lrnet? L) -4-rnet? L-3H-t? Azol-2-? L? Denarn? Na; 5-rnet ll-3-ppin din-3-lrnet? L-3H-t? Azole-2? L? Denarn? Na; 3- (6-chloro-p? R? D? N -3? Lrnet? D-5-rnet? L-3H-Cl, 3, 4] t? Ad? Ozol-2-? L denamine; chloro-2- (6-chloro-p? r? d? n-3-ylrnet? l) -2H-p? r? daz? n-3-? l? denam? na; 3- (6-chloro- p? r? dm-3-? lmet? l) -3H-benzot? azol-2-? lidenam? na; 3-p? r? d? n-3- i linet 11-3H-C1, 3,4 ] t? ad? aolol-2-ylidenarnine; 3- Cl- (6-chloro-p? pd? n -3? l) -eti H-3H-1? azol-2-i-lidenanine; 3 ~ C 1 - (6-chloro-p? -i 1? N -3? L) -et? L] -3H-Cl, 3,4] t? Ad? Azole-2-ylidenarni a; 3- C 1- ( 6-chloro-pip d? N-3-? L) -eti jl ~ t? Azol? D? N ~ 2-? L? Denam? Na; 3 -? Pd? N ~ 3-? Lrnet ll -thiazole i din- 2-? denami na; 5, 7-d? rnet? li ~ pr? d? n-3-ilinet? l-3H-l, 8"lnaft? r? d? n-2-? 6-chloro-2-pLpd? n-3-? lrnet? l ~ 2H-p? pdaz? n- 3-? l? denar? na; and 5-? net? l-3 -p? pd ? n-3? lrnet? l-3H-Cl, 3,43 t? ad? azol-2? l? denam? na
12. 12.- Fl use of a compound of the formula T or a salt or pharmaceutical prodrug cantly acceptable thereof, for preparing an effective composition in the reduction of nicotine addiction in a mammal, compound in which A is -CH (R) - and R is hydrogen or alkyl of Ci-Ce optionally substituted, wherein the substituents comprise one or more individually selected hydroxyl groups, alkoxy Ci-Ce, oxo, C2-Cβ alkanoyl and NR ^ RS; and B is a group of the NH formula in D Y-W is CH2, NH, 0, S, CH2 CH2, CH = 0H, N = CH, NH-CH2, 0CH2 or SCH2; the dotted line represents an optional link; Z is C, N, 0 or S; rn is 1? 2; n is 0, 1 or 2 with the proviso that n is 0 when Z is 0 or S, n is 1 when Z is N and n is 2 when Z is C; each R 1 and R 2 is independently selected from hydrogen, optionally substituted Ci-Cβ alkyl, optionally substituted Ci-Cβ alkoxy and optionally substituted C 2 -C β alkanoyl wherein the substituents on the alkyl or allyl groups are selected from hydroxy, Ci-Ce alkoxy, oxo, C2-Cß alkanoyl and R4 R5. or R and R2 together with the carbon atoms to which they are attached form an optionally substituted six-membered heteroaromatic ring containing at least one heterogeneous atom selected from N, S and 0 and Z is C wherein said substituents are selected from optionally substituted C 1 -Ce alkyl or optionally substituted Ci-C alkoxy wherein said substituents are selected from Ci-Ce alkyl, optionally substituted Ci-C alkoxy and optionally substituted C 2 -C e alkanoyl or R and one of R 2 together form a link with the condition that Rl and R2 can not form a bond when Z is 0 or S; R3 is hydrogen or halogen; and R * and R5 are each independently selected from hydrogen and optionally substituted Ci-Cß alkyl wherein said substituents are selected from Ci-Cß alkyl and halogen.
13. 13. The use according to claim 12, further characterized in that the compound of the formula I is selects from the group consisting of 3- (6-chloro-? pdi n-3-ylmethyl) -3H-C1, 3,4lt? ad? azole-2-ylidenamine; 3-phenyl din-3-yl eti l-3H-t? Azol -2- l denarnine; 3- (6-chloro-pen-di-3-Llrnethyl) -3H-t-azole-2-yl? Nane; 3- (6-chloro-p? R? Dm-3-? L? Net? I) -4-met? L -3H-t? Azol-2? L? Na? N? Na; 3 - (6-chloro-o-p? R? D? N-3-? L? Net? L) -4-rneti 1- 3H ~ t? Azol-2-? L? Der.a.n? Na; 5-rnet? L-3-p? Pd? N-3-? Lrnet? l-3H-t? azol-2? l? denarn? na; 3- (6-chloro-?? r? D? N-3 ~? Lrnet? L) -5 ~ rnet? L-3H- 1, 3, 43t? Ad? Ozol -2-? L idenamma; 6- chloro- 2- (6-chloro-p? Pd? N-3-ylmethyl) -2H- pin dazi n ~ 3-? li of arni a; 3- (6-chloro-p? R? Dm-3-ylmethyl) -3H-benzoth? Azole-2-? Ldenarnine; 3-p? Nd? N-3-? Lrnet? L-3H ~ Cl, 3, 4] t? Ad? Azol-2-? L? Denam? Na; 3-Cl- (6-chloro-pLpdm-3-yl) -et? L] -3H-tlazol-2-ylidenami na; 3- l- (6-chloro-p? Pdm-3? L) -et? I] -3H-Cl, 3,4] t? Ad? Azole-2-? L? Denarn? Na; 3-C i- (6-chloro-?? r? D? N -3? L) -et? L] -t? Aolol-d-n-2-yl? Denarn; 3-? r? d? n-3? lrnet? i-thiazol i di n-2-? l? denarn ina; 5, 7-d ?? net? L-l-? Pd? N -3? Lmet? I-3H-Cl, 8] naft? Pd? N ~ 2-? L? Dena; 6-chloro-2 ~? Pd? N ~ 3-? Lmet? L-2H-p? R? Daz? N -3? L? Denarn? Na; and 5-rnet? i - 3 - ?? r? d? n-3-? irnet? l-3H-Cl, 3, 4] t? ad? azole-2-? l? denarn? na.
14. 14. The compound according to claim 1, further characterized in that said pharmaceutically acceptable acid addition salts are the acid salts selected from the group consisting of hydrochloric acid, p-toluenesulfonic acid, furnanco acid, citric acid, succinic acid, salicylic acid, oxalic acid, bromidic acid, phosphoric acid, rnetansulonic acid, tartaric acid, di-p-toluoyltartápco acid and rnandélico acid. The use of a compound of the formula I wherein fl is CH (R) - and R is hydrogen or optionally substituted alkyl (C6) where the substituents comprise one or more individually selected groups of hydroxyl, alkoxy of Ci - (.6, oxo, alkanoi of C2-Ce and R * R5; and B is a group of the formula wherein Y-U is CH2, NH, 0, S, CH2 CH2, CH = CH, N = CH, NH-O-fe, 0CH2 or SCH2; the dotted line represents an optional link; Z is C, N, 0 or S; rn is 1 or 2; n is 0, 1 or 2 with the proviso that n is 0 when Z is 0 or S, n is 1 when Z is N and n is 2 when Z is C; each R1 and R2 is independently selected from hydrogen, optionally substituted Ci-Ce alkyl, optionally substituted Ci-Ci alkoxy and optionally substituted C2-Ce alkanoyl wherein the substituents on the alkyl or alkanoyl groups are selected from hydroxyl, C 1 -C 6 alkoxy, oxo, C 2 -C 6 alkanoyl and NR * RS, or R 1 and R 2 together with the carbon atoms to which they are attached form an optionally substituted six-membered heterogeneous ring containing at least one heterogeneous atom selected from N, S and 0 and Z is C wherein said substituents are selected from optionally substituted Ci-Oß alkyl or substituted C?-C alco alkoxy optionally substituted wherein said substudents are selected. select Ci-C alkyl, optionally substituted Ci-C alkoxy and optionally substituted C2-C alkanoyl or R1 and one of R2 together form a bond provided that R1 and R2 can not form a bond when Z is 0 or S; R3 is hydrogen or halogen; and R * and R5 are each independently selected from hydrogen and optionally substituted Ci-Cß alkyl wherein said substituents are selected from C? ~Calkyl and halogen, pair-to-prepare compositions for treating addictive disorders and neurological disorders or mental in a mammal. 16. The use according to claim 15, further characterized in that the compound of the formula I is selected from the group consisting of 3- (6-chloro-p? Pd? N-3-lrnethyl) -3H-Cl, 3, 4] t ad? zol- 2-? l? denarn? na; 3-p? r? d? n-3 ~? lmet? l ~ 3H-t? Azol-2-? L? Denarn? Na; 3- (6-chloro-β-pd? N-3-lrnet? L) -3H-t? Azole-2? L? Denam? Na; 3- (6-chloro-?? r? D? N-3-? Lrnet? L) -4-rnet? L-3H-t? Azol-2? L? Denarn? Na; 3- (6-chloro-p? Pd? N-3-? Lrnet ii) -4-rnet? L-3H-t? Azole-2? L? Denarn? Na; 5-rnet? L-3-p? R? D? N -3? Lrnet? L-3H-t? Aolol-2-lideneamine; 3- (6-chloro-p? Pd? N -3? Lrnet? I) -5-rnet? L-3H-Cl, 3,4] t? Ad? Ozol-2-? L? Denarn? Na; 6-chloro- 2- (B-chloro-p? P? N-3- i Irnet? L) -2H-?? p dazm-3-ylidenami na; 3- ((i-chloro-pip d-n-3-yltrilenyl) -31-l-benzot? A_iol-2 il idenarni a; 3-? Pdm-3? Lmet? L-3H-p, 3, 4"I t? Ad? Azol-2-? L? Denarn na; 3-C 1 - (6-cl oro- p? Pd? N-3- 11) -et? L] -3H-t? Azol -2-? L? Denarn? Na; 3-C i- (6-chloro-p? Pd? N ~ 3-? L) -et? P-3H-Cl, 3,43t? Ad? Azole-2- 3-C 1- (6-chloro-pen-di-3-? l) -et? l] -t? aolol-d? n-2-? l? denarn? na 3- pin din- 3- ilmetii-t? Aolol? D? N-2-? L? Denarnma; 5, 7-d? Rnet? Llp? R? D? N -3? Lrnet? I-3H ~ Cl, 8lnaft? nd? n ~ 2-? l? dena; 6-chlor '? - 2 ~ p? P d? N-3 ~? Lrnet? I-2H-p? R-? daz? n-3-ilidenarnine; and 5-rnet? l-3 - ?? r? d? n-3? lrnetH ~ 3H-1, 3, 41 thiadiazole-2-l, 111 denarn i na. 17. A composition for treating addictive disorders and neurological or mental disorders in a mammal comprising an amount of a compound of formula I effective in the treatment of addictive disorders and neurological or mental disorders wherein A is -CH (R) - and R is hydrogen or optionally substituted Ci-Ce alkyl wherein the substituents comprise one or more individually selected hydroxyl groups, Ci-C alkoxy, oxo, alkanoyl C2-Cß and NR * R5; and B is a group of the formula OR (Rl <R2>, where YU is CH2, NH, 0, S, CH2 CH2, CH = CH, N = CH, NH-CH2, 0CH2 or SCH; the dotted line represents an optional bond; Z is C, N, 0 or S, m is 1 or 2, n is 0, 1 or 2 with the proviso that n is 0 when Z is 0 or S, n is 1 when Z is N and n is 2 when Z is C; each R1 and R2 is independently selected from hydrogen, optionally substituted Ci-C3 alkyl, optionally substituted Ci-Ce alkoxy and optionally substituted C2-Ce alkanoyl wherein the substituents in the alkyl or alkanoyl groups are selected of hydroxyl, Oi-Cß alkoxy, oxo, C 2 -Ce alkanoyl and NR * R 5, or R 1 and R 2 together with the carbon atoms to which they are attached form an optionally substituted six-membered heteroaromatic ring containing at least a heterogeneous atom selected from N, S and 0 and Z is C wherein said substituents are selected from optionally substituted Ci-Ce alkyl or Ci-C alkoxy optionally substituted wherein said substituents are selected from Ci-Ce alkyl, optionally substituted Ci-C alkoxy and optionally substituted C2 -Ce alkanoyl or R and one of R2 together form a bond provided that R1 and R2 can not form a link when Z is 0 or S; R3 is hydrogen or halogen; and R * and RS are each independently selected from hydrogen and optionally substituted Ci-Cß alkyl wherein said substituents are selected from Ci-Ce alkyl and halogen. 18. The composition according to claim 17, further characterized in that the compound of formula I is selected from the group consisting of 3 ~ (6-chloro-pi pd? N-3-Llmethyl) -3H-Cl, A] thiadiazol -2-? L? Dena? N? Na; 3-pi r-i din- 3-1 lmet? L-3H ~ t? Azol-2 ~? L? Denarn na; 3- (6-chloro-? A pdin-3-? Lrnet? L) -3H-t? Azole-2-ylidenarnane; 3- (6-chloro-β? D? N-3-yltrnet-yl) -4-? Net? L-3H-t? Azol-2-? L? Denarn? Na; 3- (6-chloro-β-pd? N-3-lmeta-1) -4-rnet? L-3H-t? Azole-2? -l? Denarn? Na; 5-rnet? L-3-p? R? D? N-3-írrneti 1-3H-tlazol -2-? L? Denarn? na 3- (6- chloro-pen-din-3 -i-Irnetyl) -5-rnet? L-3H-1, 3, 4] t? Ad? Ozol-2 ~? L? Denarna; 6-chloro- 2- (6-chloro-ε-r r-d 3--3- l lrnet? L) -2H-p? R? Daz? N -3? L? Denarn? Na; 3 - (6-chloro-pin dm-3-? Lrnet? L) -3H-benzot? Azole-2-? L? Denarn? Na; 3-p? pdm-3-? lrnet? l-3H-Cl, 3, 4] t? ad? azole-2-? l? denarn? na; 3-Cl- (6-chloro-p? R? D? N -3? L) -et? L] -3H-t? Azole-2-? L? Denarn? Na; 3-L 1 - (6-chloro-p? R-? D? N ~ 3-? L) -et? L] -3H-l, 3,43t? Ad? Azole-2-? L? Denarn? Na; 3- l- (6-chloro-?? pd? N -3? L) -et? I] ~ t? Azol? D? N-2-? L? Denam? Na; 3 ~? Pd? N-3-? Lrnet? L-t? Aolol? D ~ 2 ~? Idenarnina; 5, 7-d? Met? L-l-?? pd? N -3? Lrnet? L-3H-Cl, 8] naft? Pd? N ~ 2-? L? Dena; 6-chloro-2-ppin din-3-lyrnet? L-2 H-?? p daz? N ~ 3-? L? Denarn? Na; and 5-? net? i-3-p? r? d? n-3-? lrnet? l-3H-Cl, 3, 4] t? ad? azole-2-? l? denarn? na.