MXPA04012914A

MXPA04012914A - New compounds useful for the treatment of obesity, type ii diabetes and cns disorders.

Info

Publication number: MXPA04012914A
Application number: MXPA04012914A
Authority: MX
Inventors: Katarina Beierlein
Original assignee: Biovitrum Ab
Priority date: 2002-06-20
Filing date: 2003-06-19
Publication date: 2005-03-31
Also published as: IL165051A0; RS111204A; EA200500054A1; EA008835B1; EA011581B1; CA2486989A1; EP1513828A1; WO2004000828A1; AU2003243091A1; EA200600975A1; SG156524A1; CN1662521A; BR0311952A; NZ536600A; NZ552283A; NO20050294L; NZ552282A

Abstract

The present invention relates to compounds of the general formula (I), wherein P is sulfone or sulfonamide; and A, B, W, X, Y and R3 are as defined in the description;to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the prophylaxis and treatment of medical conditions relating to obesity, type II diabetes, and/or CNS disorders, to achieve reduction of body weight and of body weight gain.

Description

NEW USEFUL COMPOUNDS FOR. THE TREATMENT OF OBESITY, DIABETES OF TYPE II AND DISORDERS OF THE SNC FIELD OF THE INVENTION The present invention concerns substituted sulfonamide and sulfone compounds, pharmaceutical compositions comprising these compounds, and the use of the compounds for the prophylaxis and treatment of medical conditions related to obesity, type 2 diabetes, and / or disorders of the central nervous system (CNS), to achieve the reduction of body weight and body weight gain, as well as cosmetic use.

BACKGROUND OF THE INVENTION Obesity is a condition characterized by an increase in body fat content resulting from excess body weight above accepted standards. Obesity is the most important nutritional disorder in the western world and represents a major health problem in all industrialized countries.

The disorder leads to increasing mortality due to the increasing incidences of diseases such as cardiovascular diseases, digestive diseases, repsiratory diseases, cancer and type 2 diabetes.

Research into compounds that reduce body weight has been increasing for many decades. One line of research has been the activation of serotononing systems, either by direct activation of serotonin receptor subtypes or by inhibition of serotonin reuptake. However, the exact peRTil of the required receptor subtype is not known. Serotonin (5-hydroxytryptamine or 5-HT), a key transmitter of the central and peripheral nervous system, modulates an amylous range of physiological and pathological functions,. Including anxiety, regulation of sleep, generation, feeding and depression. Multiple subtypes of the serotonin receptor have been identified and cloned. One of these, the 5-HT6 receptor, was cloned by several groups in 1993 (Ruat, M. et al. (1993) Biochem Biophys., Res. Commun. 193: 268-276; Sebben, M. et al. (1994) NeuroReport 5: 2553-2557). This receptor is positively coupled to adenylyl cyclase and has affinity for antidepressants such as clozapine. Recently, the effect of the 5-HT6 antagonist and 5-HT6 antisense oligonucleotides to reduce dietary intake in rats has been reported (Bentley, JC et al. (1999) Br H. Pharmac. Suppl 126, P66; Bentley , JC et al (1997) J. Psycopharmacol, Suppl A64, 255; Wooley ML et al. (2001) Neuropharmacology). Compounds with improved affinity and selectivity have been identified by the 5-HT6 receptor, for example in WO 00/34242 and by Isaac, M. et al. (2000) 6-Bicyclopiperazinyl-2-arylsulfonylindoles and 6-Bucyclopiperidinyl-1-arylsulfonylindoles derivatives as novel, potent and selective 5-HT6 receptor antagonists. Bioorganic & Medicinal Chemistry Letters 10: 1719-1721 (2000). Description of the Information J. Med. Chem. 1970, 13 (4), 592-598 describes N- (4- { [2- (diethylaminio) ethyl] amino.} - 1-naphthyl) amides; N-. { 5, 6, 7, 8- tetrahydro-4- [(3-piperidinopropyl) amino] -1-naphthyl} Related amides and amides and urea derivatives as schistosomicides. WO 99/42465 describes sulfonamide derivatives which bind to the 5-H 6 receptor and which can be used for the treatment of SSNC disorders such as anxiety, depression, epilepsy, obsessive compulsive disorders, knowledge disorders, 7ADHD, anorexia and bulimia , schizophrenia, drug abuse. WWWO 01/32646 It discloses compounds that bind to the 5-HT5 receptor and that are used for the treatment of CNS disorders and that can be used inter alia for the treatment of eating disorders.

WO 99/37623 A2 discloses compounds that bind to the 5-H 6 receptor and which are used for the treatment of CNS disorders and which can be used inter alia for the treatment of eating disorders. WO 99/42465 3 describes compounds that bind to the 5HT6 receptor and that are used for the treatment of CNS disorders and that can be used inter alia for the treatment of eating disorders. EP 0 815 861 describes compounds that bind to the 5-HT6 receptor and that are used for the treatment of CNS disorders. WO 99/02502? 2 describes compounds which bind to the 5-HT6 receptor and which are used for the treatment of CNS disorders and which can be used inter alia for the treatment of eating disorders. WO 98/27081 Al, describes compounds that bind to the 5-HT6 receptor and that are used for the treatment of CNS disorders and that can be used inter alia for the treatment of eating disorders. EP 0701819 describes compounds that bind to the 5-HTiD receptor and that are used for the treatment of CNS and obesity disorders. US 6,191,141 and WO 01/12629 disclose compounds that bind to the 5-HT 6 receptor and that are used for the treatment of CNS disorders.

DESCRIPTION OF THE INVENTION Surprisingly it was found that compounds of formula (I) show affinity for the 5-H 6 receptor as antagonists at low nanomolar intervals. The compounds according to the invention and their pharmaceutically acceptable salts have activities of 5-HT6 receptor antagonists, agonists and partial agonists and are believed to be of potential use in the treatment or prophylaxis of obesity and type 2 diabetes, for achieve the reduction of body weight and body weight gain, as well as in the treatment or prophylaxis of disorders of the central nervous system such as anxiety, depression, panic attacks, memory disorders, knowledge disorders, disorders of the sleep, migraine, anorexia, bulimia, obsessive compulsive disorders, psychosis, Alzheimer's disease, Parkinson's disease, Huntington's disease, chorea and / or schizophrenia, Hyperactive Disorders and Deficit of Attention (ADHD), drug abuse. The reduction of body weight and body weight gain (eg, treatment for body weight disorders) is achieved inter alia by the reduction of dietary intake. As used herein, the term "body weight disorders" is RTIE to disorders caused by an imbalance between energy intake and energy consumption, resulting in abnormal body weight (eg, excessive). Such disorders of body weight include obesity. Definitions Unless otherwise stated, the term "Ci_6-alkyl" (or A, C2-6-alkenyl ") denotes a straight or branched chain hydrocarbon group having from 1 to 6 carbon atoms (or 2). to 6 carbon atoms). Examples of said lower alkyls include methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, t-butyl and straight and branched chain pentyl and hexyl. The alkenyl groups have one or more carbon-carbon double bonds in the chain. Unless stated or otherwise indicated, the term "Ci-s-alkoxy" denotes a straight or branched chain alkoxy group having from 1 to 6 carbon atoms. Examples of said lower alkoxy include methoxy, ethoxy, n-propoxy, iso-proporto, n-butoxy, iso-butoxy, sec-butoxy, t-butoxy and straight and branched chain pentoxy and hexoxy. Unless otherwise stated or indicated, the term vCi_5-alkoxyalkyl "denotes a straight or branched chain alkoxyalkyl group having from 1 to 6 carbon atoms Examples of said lower hydroxyalkyl include methoxymethyl, ethoxymethyl, iso-propoxymethyl straight and branched chain pentoxymethyl, t-butoxyethyl and straight-chain pentoxymethyl The term "C2-6_alkenyl" as used herein refers to straight and branched chain aleunyl groups containing from 2 to 6 goat atoms. Typical include vinyl, allyl, 2,3-dimethylallyl, 1-butenyl, 1-pentenyl, and 1-hexenyl groups. The expression wC2-6_alkynyl "'as used herein refers to straight and branched chain alkynyl groups. containing from 2 to 6 carbon atoms. Typical examples include ethynyl, 1-propynyl, 1-butynyl, 1-pentynyl, and 1-exynyl groups. Unless stated otherwise, the term "halogen" means fluorine, chlorine, bromine or iodine. The term "alkylhalide" refers to an alkyl group substituted with one or more halogen groups (e.g., F, Cl, Br, I). The term "C3-7-cycloalkyl" denotes a cyclic alkyl group having a ring size of C3 to C7, which may be saturated or partially unsaturated. Examples of said cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclopentadienyl, cyclohexyl, methylcxclohexyl, cyclohexenyl, cyclohexadienyl, and cycloheptyl. The term C5-io-cycloalkenyl "denotes a cyclic alkenyl group having a ring size of C5 to Cio. Examples of said cycloalkenyl include 1-cyclopentyl groups, 2-cyclopentenyl, 1-cyclohexenyl, 1-cycloheptenyl, 1-cyclooctenyl, 1-cyclononenyl, and 1-cyclodecenyl. The term "heterocyclic" refers to a hydrocarbon ring system containing 4 to 8 elements in the ring having at least one heteroatom (eg, S, N, or O) as part of the ring. Includes saturated, unsaturated, aromatic, and non-aromatic heterocycles. Suitable heterocyclic groups include thienyl, furyl, pyridyl, pyrrolidinyl, imidazolyl, pyrazolyl, piperidyl, azepinyl, moRTolinyl, pyranyl, dioxanyl, pyridazinyl, and piperazinyl. Unless otherwise stated, the term "Maryl" refers to a hydrocarbon ring system having at least one aromatic ring Examples of aryl groups include phenyl, cinnamyl, pentalenyl, indenyl, 1- naphthyl, 2- naphthyl, anthryl and phenanthryl The term "heteroaryl" refers to a hydrocarbon ring system having at least one aromatic ring containing at least one heteroatom such as 0, N, or S. Examples of heteroaryl groups include furyl, pyrrolyl groups , thienyl, oxazolyl, imidazolyl, thiazolyl, pyridinyl, pyrimidinyl, quinazolyl, and indolyl Compounds of Formula I An object of the present invention is a compound having the general formula (I): or a pharmaceutically acceptable salt thereof, wherein: in ring B is wherein D is a 5-membered heteroaryl or heterocyclic ring, the heteroaryl ring comprises one or two atoms selected from the group consisting of nitrogen, sulfur and oxygen, with the proviso that D contains an oxygen atom, D is heteroaryl; each W is independently -N-, - (CH-, -C- provided that no more than three W groups are -N- in both A and B rings together, P is any one of formula (a), (b) ) or (c) (a) (b) (c) where x = 0, 1, or 2 and y = 0, 1, or 2; and P and R3 can be attached to any carbon atom that allows substitution in one of the rings A- or B- or in both or when ring A contains at least one nitrogen atom and P is (c), then P it can be fixed to any nitrogen in ring B that allows substitution; the links with ntrecortada line denote that P and R3, respectively, can be fixed either to ring A or B; but each of P or R3 may not be linked simultaneously to both rings A and B; R1 is (a) Ci-6-alkyl, (b) Ci-6-alkoxyalkyl (c) Ci_s-hydroxyalkyl straight or branched chain, (d) Ci_6-straight or branched chain alkylhalides, (e) aryl carbonylmethyl, ( f) C3-7-cycloalkyl, which is optionally unsaturated, (g) Cs-v-cycloalkyl-Ci-e-alkyl, wherein the cyclic ring is optionally partially unsaturated, or (h) an Ar group wherein Ar is (a) phenyl, (b) l-naphthyl, (c) 2-naphthyl, (d) aryl-C! -6-alkyl, (e) cinnamyl (f) a mono- or bicyclic heterocyclic ring, partially saturated or fully saturated, optionally aromatic of 5 to 7 elements, each containing 1 to 4 heteroatoms, selected from oxygen, sulfur and nitrogen, (g) a bicyclic ring system comprising at least one heterocyclic ring in accordance with (f) and an Ar group, wherein the group Ar is substituted in one or more positions with (a) H, X or Y, or (b) an optionally aromatic partially or fully saturated heterocyclic ring to 7 elements, containing 1 to 4 heteroatoms selected from oxygen nitrogen or sulfur; R2 is (a) H, (b) Ci_s-alkyl, (c) C2-6-alkoxyalkyl, (d) Ci-6-hydroxyalkyl straight or branched, or (e) Ci-6-straight or branched alkylhalides; (f) an Ar group, or R1 and R2 are linked to form a -CH2 group where v is 0-2, X and Y are independently (a) H, (b) halogen, (c) Ci-6-alkyl, (d) CF3, (e) hydroxy (f) Ci-6-alkoxy, (g) C2-6-alkenyl, ih) phenyl, (i) phenoxy, (j) benzyloxy, (k) benzoyl, (1) -0CF3, (m) -CN, (n) straight or branched Ci-ehydroxylalkyl, (o) Ci-6-straight or branched alkylhalides, (P) -H2, (q) -NHR4, (r) -NR4R5, (s) -N02, (t) -CONRR5, (u) -NHS02R4, (v) ) -NR4COR5, (x) -S02NR4R5, (z) -C (= 0) R4, (ab) -S (0) nR4, where n is 0, 1, 2 or 3, (ac) -S- ( Ci-s) alkyl, 0 (ad) -SCF3; and R4 and R5 are independently (a) H, (b) Ci-6-alkyl, (c) C3-7_cycloalkyl, 0 (d) Ar, as defined above for alternatively, R4 and R5 are linked to form a group - CH2OCH2-, -CH2CH2OCH2CH2- or (CH2) 3 ~ 5; R3 is a group selected from any one of wherein R3 is optionally substituted on each carbon atom that allows substitution with groups Rq, wherein Rq is independently H, or (Ci-e-alkyl, and wherein Rq groups may be preseted on the same carbon atom simultaneously, where q = 1, 2, 3, 4, 5 or 6,? a = 1 or 2, and n = 0, 1 or 2, R6 is independently (a) H (b) Ci-6-linear or branched alkyl, (c) benzyl (d) -CH2-CH2-OH, or (e) -CH2-CH2-0-Ci-6-alkyl; P and R3 may be attached to the same ring or to different rings of rings A and B; provided that when P is and P and R3 are both fixed to ring A in the meta- or para- position in relation to each other, then R3 is selected from any one of where the B ring is (a), then P and R3 are simultaneously fixed to the same ring A or B; where the B ring is where y = 0, then P and R3 are fixed to the different rings A and B; when the ring system A + B is benzofuran or benzothiophene, and P is R \ '(C) and is fixed at position 3 in the ring system A + B, and R3 is a group selected from any one of?' and it is fixed in position 7 in the annular system A + B, then y = 1 or 2; when the annular system A + B is indole, and (P is and P is fixed in position 3 in the annular system A + B, and B3 is a group selected from any one of and R3 is fixed in position at any one of positions 5, 6 or 7 in the ring system A + B, then y = = Ar is partially saturated bicyclic heterocyclic ring containing an atom of N in Ar can not be attached to the atom from S to P; with the proviso that when rings A and B are both phenyl, P is any one of formula (a) or (c) substituted at position 7 in the naphthalene ring, then R3 is not substituted in position 1 in the ring naphthalene; and with the proviso that: when the ring D e sun pyrrole ring, P is of the formula (c), then B3 is not of the formula substituted in position 3 in the pyrrole ring. A naphthalene ring has the following position numbers: where Pi-Pg denotes the position on the naphthalene ring. A pyrrole ring, when connected to a ring A, has the following position numbers: wherein P1-P3 denotes the position on the pyrrole ring. It is preferred that: R1 is (a) cy-6-alkyl, or (e) an Ar group; Ar is (a) phenyl (b) 1-naphthyl, (c) 2-naphthyl, or (f) a partially or fully saturated, optionally aromatic, 5-7-membered eteroe-cyclic ring containing 1 to 4 heteroatoms, selected from oxygen, nitrogen and sulfur, wherein the group Ar is substituted in one or more positions with (a) H (b halogen (c Ci-6-alkyl, (d -CF3, (f Ci-6-alkoxy, (g C2-6 -alkenyl (preferably C2-4-alkenyl), (i-0CF3, (m Ci_6-hydroxyalkyl straight or branched, (n-phenyloxy, (or benzyloxy, (v-NRCOR5, (x -SO'NR4R5, (z -C ( = 0) R4, (ab) -S (0) nR4 / where n is 0, 1, 2 or 3; (ac) -S- (Ci_6) -alkyl, or (ad) -SCF3; R2 is (a ) H, or (b) Ci-e-alkyl, or R1 and R2 are bonded to form a group X and Y are H; R4 and R5 are independently from each other H or C1-3-alkyl, and R3 is selected from one any of wherein R3 can be substituted at each carbon atom that allows substitution with groups Rq, wherein Rq is independently H, or Ci_5-alkyl, and wherein two Rq groups can be simultaneously present on the same carbon atom, wherein q = 1 or 2, m = 1 or 2 n = 0, and Rs is independently (a) H, (b) Ci-6-alkyl (preferably Ci_3-alkyl), in particular methyl, (d) -CH2-CH2 -0H, o It is especially preferred that R3 be selected from any one of wherein R3 can be substituted on each carbon atom that allows substitution with groups Rq, wherein Rq is independently H, or Ci_2-alkyl, and wherein two Rq groups can be present on the same carbon atom simultaneously, wherein q = 1 or 2, m = 1 or 2; and R6 is independently (a) H, (b) Ci-3-alkyl, (d) -CH2CH2-OH, or (e) -CH2-CH2-0CH3. It is preferred that R3 be selected from the group consisting of any one of wherein R3 can be substituted on each carbon atom that allows substitution with Rg groups, wherein Rq is independently H, or Ci_6-alkyl, and wherein two Rq groups can be simultaneously present on the same carbon atom, wherein q = 1 or 2, m = 1 or 2, n = 0, and R6 is independently (a) H, (b) Ci-3-alkyl, (d) -CH2-CH2-OH, or (e) -CH2 -CH2-OCH3. It is also preferred that R3 be selected from any one R6 is independently (a) H, (b) Ci-3-alkyl, or (d) -CH2-CH2-OH, or (e) -CH2-CH2-0CH3. It is preferred that R6 is H or methyl. It is also preferred that R3 is piperazine homopiperazine; 2,6-dimethylpiperazine; 3,5-dimethylpiperazine; 2,5-dimethylpiperzain; 2-methylpiperazine; 3- methylpiperazine; 2,2-dimethylpiperazine; 3, 3-dimethylpiperazine; piperidine; 1 2, 3, 6-tetrahydro-pyrazine; or 4-pyrrolidin-3-yloxy. It is preferred that the groups Y and X are fixed to any unsubstituted carbon atom. It is preferred that D is pyrrolyl, thienyl or furanyl.

It is preferred that P is where R1, x, e and are as defined in claim 1. It is also preferred that P is wherein R1 and R2 are as defined in claim 1. It is preferred that R2 is H. Another object of the present invention is a compound of the general formula (II) wherein R1, x, y, X / and Y are as defined in the claim as defined in claim 2. It is preferred that y = 0 and x = 2. Another object of the present invention is a compound of the general formula (III) wherein R, x, y, X, and Y are as defined in claim 1, and R3 is as defined in claim 2. It is preferred that y = 0 and x = 2. Another object of the present invention is a composed of the general formula (IV) wherein P is of the formula (c), R1, x, y, X, and Y are as defined in claim 1, and R3 is as defined in claim 2, and wherein D, is a heteroaryl ring of five elements, the ring comprises one or two atoms selected from the group consisting of nitrogen, sulfur and oxygen; and when the heteroaryl ring comprises one or two nitrogen atoms, a R6 group is attached to any nitrogen atom that permits substitution. It is preferred that D is a thiophene and P is attached to ring D, giving a skeleton as any of the following: It is preferred that D is pyrrole and P is attached to the nitrogen atom in ring D, giving a skeleton as any of the following: Another object of the present invention is a general formula compound (V) wherein P is of the formula (c) as defined in claim 1, R1, x, y, X and Y, and R3 are as defined in claim 1, and wherein D is a five-membered heteroaryl ring , the heteroaryl ring comprises one or two atoms selected from the group consisting of nitrogen, sulfur and oxygen; and when the heteroaryl ring comprises one or two nitrogen atoms, a R6 group is attached to any nitrogen atom that permits substitution.

Another object of the present invention is a compound of the general formula (V) wherein P is of the formula (a) or (b) as defined in claim 1, preferably wherein R2 is H, X, Y, and R3 are as defined in claim 1, and wherein D is a five-element heteroaryl ring, the heteroaryl ring comprises one or two atoms selected from the group consisting of nitrogen, sulfur and oxygen; and when the heteroaryl ring comprises one or two nitrogen atoms, a R6 group is attached to any nitrogen atom that permits substitution. Another object of the present invention is a compound of the general formula (VI) wherein P is of the formula (a) or (b) as defined in claim 1, preferably wherein R2 is H, X and Y are as defined in claim 1, and R3 is as defined in the claim 2. Another object of the present invention is a compound of the general formula (VII) (vn) wherein P is of formula (a) or (b) as defined in claim 1, preferably wherein] ¾ is H, X and Y are as defined in claim 1, and R3 is as defined in Claim 4. Another object of the present invention is a compound of the general formula (VIII) (HIV) wherein P is of the formula (a) or (b) as defined in claim 1, preferably wherein R2 is H, X, Y, and R3 are as defined in claim 1. Another object of the present invention is a compound of the general formula (IX) wherein R1 in the formula (IX) is: (a) H, (b) Ci-e-alkyl, (c) benzyl, (d) -CH2-CH2-0H, or (e) -CH2-CH2-0 -C¾, and wherein P is of the formula (a) or (b) as defined in claim 1, preferably wherein R2 is H, X, Y, and R3 are as defined in claim 1. Other object of the present invention is a compound of the general formula (X) wherein P is of the formula (a) or (b) as defined in claim 1, preferably wherein R2 is H, X, Y, and R3 are as defined in claim 1. Another object of the present invention is a compound of the general formula (XI) wherein P is of formula (a) or (b) as defined in claim 1, preferably wherein R2 is H, X and Y are as defined in claim 1, and R3 is as defined in claim 4. Another object of the present invention is a compound of the general formula (XII): or a pharmaceutically acceptable salt thereof, wherein P and R3 are attached to the same ring or rings different from rings A and B, wherein A, B, Y, P, and R3 are as defined in claim 1. Preferred compounds of the formula (II) are 6-Benzenesulfonyl-4-piperazin-1-yl-quinoline hydrochloride; 6 - [(2-fluorophenyl) sulfonyl] -4-piperazin-1-yl-quinoline hydrochloride; 6- (1-naphthylsulfonyl) -4-piperazin-1-yl-quinoline hydrochloride; Hydrochloride 6- [. { 3, 4-dichlorophenyl) sulfonyl] -4-piperazin-1-yl-quinoline; 6 - [(3,5-Dimethylphenyl) sulfonyl] -4-piperazin-1-yl-quinoline hydrochloride; 6- [(2-Chloro-6-methylphenyl) sulfonyl] -4-piperazin-1-yl-quinoline hydrochloride; 6- [(4-chlorophenyl) sulfonyl] -4-piperazin-1-yl-quinoline hydrochloride; 6- [(2-methyl, 4-tert-butylphenyl) sulfonyl] -4-piperazin-1-yl-quinoline hydrochloride; 6- [(3,4-Dimethylphenyl) sulfonyl] -4-piperazin-1-yl-quinoline hydrochloride; 6 - [(2, 3-Dichlorophenyl) sulfonyl] -4-piperazin-1-yl-quinoline hydrochloride; 6 - [(4-tert-Butylphenyl) sulfonyl] -4-piperazin-1-yl-quinoline hydrochloride; Hydrochloride 6- [. { 4- isopropylphenyl) sulfonyl] -4-piperazin-1-yl-quinoline; (4-Piperazin-1-yl-6- { [4- (trifluoromethyl) phenyl] sulfonyl} quinoline hydrochloride; 6- [(4-tert-butylphenyl) sulfonyl] -4- (1, 4- diazepan-1-yl) quinoline; and 4- (1, 4-diazepan-1-yl.) - 6 - [(4-isopropyl-phenyl) -sulfonyl] -quinoline, Preferred compounds of the formula (III) are 7- (2-chloro-6-methyl-benzenesulfonyl) -1- piperazin-1-yl-isoquinoline hydrochloride; 7- (2-t-Butyl-benzenesulfonyl) -1-piperazin-1-yl-isoquinoline hydrochloride; 7- (3,4-dichlorobenzenesulfonyl) 1- piperazin-1-yl isoquinoline; 7- (2,4-dimethylbenzenesulfonyl) -1 piperazin-1-yl isoquinoline hydrochloride; 2,5-dimethylbenzenesulfonyl) -1-piperazin-1-yl-isoquinoline; 7- (p-chlorobenzenesulfonyl) -1-piperazin-1-yl isoquinoline hydrochloride; 7- benzenesulfonyl-1- [1, 4] diazepan-1-yl isoquinoline; 7- (4-tert-Butyl-benzenesulfonyl) -1] 1,4-diazepam-1-yl- hydrochloride isoquinoline; 7- (2-Chloro-6-methyl-benzenesulfonyl) -1- [1,4] -diazepan-1-yl-isoquinoline hydrochloride; 7- (3,5-dimethylbenzenesulfonyl) -1 [1,4] diazepan-1-yl isoquinoline hydrochloride; 7- (3,4-dichlorobenzenesulfonyl) -1 [1,] diazepan-1-yl isoquinoline hydrochloride; 7- (4-Chlorobenzenesulfonyl) -1] 1,4-diazepane-1-yl isoquinoline hydrochloride 7- (3,4-dimethylbenzenesulfonyl) -1 [1,4] diazepam-1 hydrochloride - il-isoquinoline; 7- (2-tert-Butyl-Benzenesulfonyl) -1-Hydrochloride [1,4] diazepan-1-yl isoquinoline; 7- Benzenesulfonyl-1-piperazin-1-yl-isoquinoline hydrochloride; and 7- (4-tert-Butyl-benzenesulfonyl-1-piperazin-1-yl-isoquinoline hydrochloride; Preferred compounds of the formula (IV) are 4- (1, 4-diazepane-1-yl) -2-hydrochloride. phenylsulfonyl) thieno [3, 2-c] pyridine; 4- (1, 4-diazepan-1-yl) -2- [ {3,4-dichlorophenyl) sulfonyl] thieno [3, 2-c] pyridine hydrochloride; 4- (1, 4-diazepan-1-yl) -2- [4- tert-butylphenylsulfonyl] thieno [3, 2-c] pyridine hydrochloride; 4- (1, 4-diazepan-1-yl) -2- [4- tert-butylphenylsulfonyl] thieno [3, 2-c] pyridine hydrochloride; 4- (1, 4-diazepan-1-yl) -2- [3,4-dimethylphenylsulfonyl] thieno [3, 2-c] pyridine hydrochloride; 2- [(4-Bromophenyl) sulfonyl-] 4- (1-diazepan-1-yl) -thieno [3, 2-c] pyridine hydrochloride; 2- (Phenylsulfonyl) -4- piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 2- (3-methoxy-benzenesulfonyl) -4-piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 2- (4-methoxy-benzenesulfonyl) -4-piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 4- Piperazin-1-yl-2- hydrochloride. { [(4-trifluoromethyl) phenyl] sulfonyl} thieno [3, 2- c] pyridine; 2- [(2-tert-Butylphenyl) sulfonyl] -4-piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 2- [(3,4-Dichlorophenyl) sulfonyl] -4-piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; 2- [(4-tert-Butylphenyl) sulfonyl] -4-piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 2- (1-Naphthylsulfonyl) -4- piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 2- [(3-fluorophenyl) sulfonyl] -4-piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 2- (Mesitylsulfonyl] -4- piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 2- [(2-methoxyphenyl) sulfonyl] -4-piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 2- [(2,4-dimethoxyphenyl) sulfonyl] -4-piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 2- [(2,4-dimethylphenyl) sulfonyl] -4-piperazine-1-hydrochloride - iltieno [3, 2-c] pyridine; 2- [(2,5-dimethylphenyl) sulfonyl] -4-piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 2- [(2-ethylphenyl) hydrochloride] ) sulfonyl] -4-piperazin-1-ylthieno [3, 2-c] pyridine; 4- (piperazinyl) -2- (3-methoxybenzyl-sulfonyl) -thienopyridine hydrochloride; 2- (benzylsulfonyl) -4-hydrochloride pipe azin-1-ylthieno [3, 2-c] pyridine; 4- piperazin-1-yl- 2 { [4- (trifluoromethyl) benzyl] sulfonyl} thieno hydrochloride [3,2-c] pyridine; [(3-bromobenzyl) sulfonyl] -4-piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 2- [. {2-3-difluorobenzyl) sulfonyl] -4- piperazine hydrochloride 1- iltieno [3, 2-c] pyridine; [(4-bromobenzyl) sulfonyl] -4-piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 2- Hydrochloride. { [2,5-bis (trifluoromethyl) benzyl] sulfonyl} - 4- piperazin-1-ylthieno [3, 2-c] pyridine; 2- [(4-methylbenzyl) sulfonyl] -4-piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 2- Hydrochloride. { [5- Chloro-2- (trifluoromethyl) benzyl] sulfonyl} - 4- piperazin-1-ylthieno [3, 2-c] pyridine; 2- [(3,5-dimethoxybenzyl) sulfonyl] -4- piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 2- [(2-Naphthylmethyl) sulfonyl] -4-piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 4- Piperazin-1-yl-2- hydrochloride. { [4- (1, 2, 3-thiadiazol-4-yl) benzyl] sulfonyl} thieno [3, 2-c] pyridine; 1- (4-pyrrolidin-1-ylphenyl) -2- [(4-piperazin-1-ylthieno [3,2-c] pyridin-2-yl) sulfonyl] ethanone hydrochloride; and 1- [4- (Diethylamino) phenyl] -2- [(4-piperazin-1-ylthieno [3, 2-c] pyridin-2-yl) sulfonyl] ethanone hydrochloride. Also preferred compounds of formula (IV) are 1- (4-methylphenylsulfonyl) -4-piperazin-1-yl-1H-pyrrolo [3, 2-c] pyridine hydrochloride; 1- (3-Chloro-2-methylphenylsulfonyl) -4- piperazin-1-yl-1H-pyrrolo [3, 2-c] pyridine hydrochloride; 1- (3,4-Dimethoxyphenylsulfonyl) -4-piperazin-1-yl-1H-pyrrolo [3, 2-c] pyridine hydrochloride; 4- (4-Piperazin-1-yl-pyrrolo [3, 2-c] pyridin-1-sulfonyl) -benzonitrile hydrochloride; 1- (4,5-dichlorothiophene-2-sulfonyl) -4- piperazin-1-yl-1H-pyrrolo [3, 2-c] pyridine hydrochloride; 1- (2-Chloro-4-fluorophenylsulfonyl) -4- piperazin-1-yl-1H-pyrrolo [3, 2-c] pyridine hydrochloride; 1- phenylmethanesulfonyl-4-piperazin-1-yl-1H-pyrrolo [3, 2-c] pyridine hydrochloride; 1- (5-chloro-thiophene-2-sulfonyl) -4-piperazin-1-yl-1H-pyrrolo [3, 2-c] pyridine hydrochloride; 1- (5-Chloro-thiophen-2-sulfonyl) -4-piperazin-1-yl-1H-pyrrolo [3, 2-c] pyridine hydrochloride; 1- (4-Butyl-benzenesulfonyl) -4-piperazin-1-yl-1H-pyrrolo (3, 2-c) pyridine hydrochloride; 1- (4-phenoxy-benzenesulfonyl) -4-piperazin-1-hydrochloride il- 1H- pyrrolo {3, 2- c) pyridine; 1- (Phenylsulfonyl) -4- piperazin-1-yl-1H-pyrrolo [3, 2-c] pyridine hydrochloride; 1- [(4-chlorophenyl) sulfonyl] -4-piperazin-1-yl-1H-pyrrolo [3, 2-c] pyridine hydrochloride; 1- [(4-methoxyphenyl) sulfonyl] -4-piperazin-1-yl-1H-pyrrolo [3, 2-c] pyridine hydrochloride; 1- [(2-methoxy-5-methylphenyl) sulfonyl] -4- piperazin-1-yl-1H-pyrrolo [3, 2-c] pyridine hydrochloride; and 4- Piperazin-1-yl-1- Hydrochloride. { [2- (trifluoromethyl) phenyl] sulfonyl} - 1H- pyrrolo [3, 2- c] pyridine. Preferred compounds of formula VI are N- (4-methylphenyl) -4- (4-methylpiperazin-1-yl) thieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; P-Tolylamide 2-bromo-4- (4-methyl-piperazin-1-yl) -thieno [3, 2-c] pyridin-3-sulfonic acid hydrochloride; 4- (4-methylpiperazin-1-yl) -n-phenylthieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; (3-Fluoro-5-trifluoromethyl-phenyl) -amide 4-piperazin-1-ylthieno [3, 2-c] pyridine-2-sulfonic acid hydrochloride; (4-Chloro-phenyl) -amide 4-piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonic acid hydrochloride; (4-isopropyl-phenyl) -amide 4-piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonic acid hydrochloride; P-Tolylamide 4-piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonic acid hydrochloride; 4- (4-methyl-piperazin-1-yl) -N- (2-cyclohex-1-en-1-ylethyl) -thieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; 2- ('4- (4-methyl-piperazin-1-yl) thieno [3, 2-c] pyridin-2-ylsulfonyl) -1,2,4,4-tetrahydroisoquinoline hydrochloride; 4- (4-methylpiperazin-1-yl) -N- (2-thien-2-ylethyl) thieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; 4- (4-methylpiperazin-1-yl) -N- [1- (1-naphthyl) ethyl] thieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; 4- (4-methylpiperazin-1-yl) -N- (4-hexylphenyl) thieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; N- (3-chlorobenzyl) -4- (4-methylpiperazin-1-yl) thieno [3, 2-c] pyridin-2-sulfonamide; 4- (4-methylpiperazin-1-yl) -N- [1- (4-fluorophenyl) ethyl] thieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; N- (2, 3-difluorobenzyl) -4- (4-methylpiperazin-1-yl) thieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; 4- (4-methylpiperazin-1-yl) -N- (4-chloro-2,5-dimethoxyphenyl) thieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; 2-Bromo-4- (4-methyl-piperazin-1-yl) -N- (2-cyclohex-1-en-1-ylethyl) -thieno [3, 2-c] pyridin-3-sulfonamide hydrochloride; 2-Bromo-4- (4-methyl-piperazin-1-yl) -N- [(1S) -1- (2-naphthyl) -ethyl] -thieno [3, 2-c] pyridine-3-sulfonamide hydrochloride; 2-Bromo-4- (4-methyl-piperazin-1-yl) -N- [1- (4-fluorophenyl) -ethyl] -thieno [3, 2-c] pyridin-3-sulfonamide hydrochloride; 2- Bromo-4- (4-methylpiperazin-1-yl) -N- [2,4, 5-trimethoxyphenyl) thieno [3, 2-c] pyridin-3-sulfonamide; N- (3,4-dichlorophenyl) -4- piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; N- (2, 4-difluorophenyl) -4- piperazin-1-ylthieno [3, 2-c] pyridin-2-ylphonamide hydrochloride; 4- Piperazin-1-yl- N- [3- (trilumphoromethyl) phenyl] thieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; N- (3-ethylphenyl) -4- piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; N- (3,4-dimethoxyphenyl) -4-piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; N- (4-bromo-2-methylphenyl) -4-piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; 2- (4-Piperazin-1-ylthieno [3,2- c] pyridin-2-sulfonyl) -1,2,3-tetrahydro-isoquinoline hydrochloride; (2-thiophene-2-yl-ethyl) -amide-4-piperazin-1-ylthieno [3, 2-c4-pyridin-2-sulphonic acid hydrochloride; (4-Chloro-2, 5-dimethoxy-phenyl) -amide-4-piperazin-1-ylthieno [3, 2-c] pyridine-2-sulphonic acid hydrochloride; Chlorohydrate of phenethylamide 4-piperazin-1-ylthieno [3, 2-c] pyridin-2-sulphonic acid hydrochloride; (2,6-diethyl-phenyl) -amide 4-piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonic acid hydrochloride; (3-phenylpropyl) -amide 4-piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonic acid hydrochloride; (3, 3-Diphenyl-propyl) -amide 4-piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonic acid hydrochloride; [2- (5-Methoxy-1H-indol-3-yl) -ethyl] -amide 4- piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonic acid hydrochloride; 4-Trifluoromethyl-benzylamide acid hydrochloride 4- piperazin-1-ylthieno [3,2-c] pyridin-2-sulfonic acid; Hydrochloride - of benzyl ethyl amide 4- piperazin-1-ylthieno [3, 2-c] pyridine-2-sulphonic acid; N- (3-ethylphenyl) -4- piperazin-1-ylthieno [3, 2-c] pyridin-3-sulfonamide hydrochloride; N- (4-isopropylphenyl) -4- piperazin-1-ylthieno [3, 2-c] pyridin-3-sulfonamide hydrochloride; N- (4-methylphenyl) -4- (pyrrolidin-3-yloxy) thieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; N- (4-methylphenyl) -4- (pyrrolidin-3-yloxy) thieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; N- (4-methylphenyl) -4- (piperidin-4-yloxy) thieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; N- (2, 3-difluorobenzyl) -4-piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; N- (3-chlorobenzyl) -4- piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; Phenylamide 4-pyridin-1-ylthieno [3, 2-c] pyridin-2-sulfonic acid hydrochloride; 4- (4-tert-Butyl-phenyl) -amide hydrochloride 4-piperazin-1-ylthieno [3, 2-c] pyridin-2-sulphonic acid hydrochloride; Phenylamide acid hydrochloride 4- (4-methyl-piperazin-1-yl) -thieno [3,2-c] pyridin-2-sulphonic acid; (3-chloro-phenyl) -amide 4- (4-methyl-piperazin-1-yl) -thieno [3, 2-c] pyridin-2-sulfonic acid hydrochloride; Phenylamide 2-bromo-4- (4-methyl-piperazin-1-yl) -thieno [3, 2-c] pyridin-3-sulfonic acid hydrochloride; 4- (4-Methyl-piperazin-1-yl) -thieno [3, 2-c] pyridine-3-sulfonic acid hydrochloride (4-methylphenyl) -amide; N-Phenyl-7- piperazin-1-ylthieno [2, 3-c] pyridin-2-sulfonamide hydrochloride. Preferred compounds of the formula (VII) are N- (4-methylphenyl) -4- piperazin-1-ylfuro [3, 2-c] pyridin-2-sulfonamide hydrochloride; N-phenyl-4- piperazin-1-ylfurohydrochloride [3, 2- c] pyridin-2-sulfonamide; and N-phenyl-7- piperazin-1-ylfuro hydrochloride [2, 3- c] pyridin-2-sulfonamide. A preferred compound of the formula (VIII) is Phenylamide 4-piperazin-1-yl-thiazolo [4,5- c] pyridine-2-sulphonic acid hydrochloride. Preferred compounds of the formula (IX) are N- (4-methylphenyl) -4- piperazin-1-yl-1H-pyrrolo [3, 2-c] pyridin-2-sulfonamide hydrochloride; N-Phenyl-4-piperazin-1-yl-1H-pyrrolo [3, 2-c] pyridin-2-sulfonamide hydrochloride; and N-phenyl-7-piperazin-1-yl-1H-pyrrolo [2, 3-c] pyridin-2-sulfonamide hydrochloride. Preferred compounds of formula (X) are 4-chloro-N- [4- (pyrrolidin-3-yloxy) -1-naphthyl] -benzenesulfonamide hydrochloride; 4-methoxy-N- [4- (pyrrolidin-3-yloxy) -1-naphthyl] -benzenesulfonamide hydrochloride; 5- Chloro- N- [4- (pyrrolidin-3-yloxy) -1-naphthyl] thiophene-2-sulfonamide hydrochloride; 4- Chloro-N- [4- (piperidin-3-yloxy) -1-naphthyl] benzenesulfonamide hydrochloride; 4- Methoxy-N- [4-piperidin-3-yloxy) -1-naphthyl] benzenesulfonamide hydrochloride; 5- Fluoro-2-methyl-N- [4- (piperidin-4-yloxy) -1-naphthyl] benzenesulfonamide hydrochloride; 5- Chloro-N- [4- (piperidin-4-yloxy) -1-naphthyl] thiophene-2-sulfonamide hydrochloride; 4- Chloro-N- hydrochloride. { 4- [(3S) -pyrrolidin-3-yloxy] -1-naphthyl} benzenesulfonamide; and 4-Chloro-N- Hydrochloride. { 4- [(3R) -pyrrolidin-3-yloxy] -1- naphthyl} benzenesulfonamide.

Another object of the present invention is a process for the preparation of a previous compound, the method comprises the steps of: (a) Mitsonobu reaction of 4-nitro-1-naphthol von 3-idroxypyrrolidine protected with Boc or 4-hydroxypiperidine; (b) reduction of the nitro group in the nitronaphthalene obtained in step (a) to form an aminonaphthalene derivative; and (c) synthesis of a sulfonamide by reaction of the aminonaphthalene obtained in step (b) with a suitable sulfonyl chloride. Another object of the present invention is a process for the preparation of a previous compound, wherein P is said method comprises the steps of: Preparation of the heteroaromatic 5-membered ring fused with substituted pyridine with halogen, reduction of an aromatic nitro group; aromatic nucleophilic substitution with a thiol via a diazointermediate; oxidation of the thiol derivative to a sulfone; introduction of a halogen atom by electrophilic aromatic substitution; aromatic nucleophilic substitution of the halogen with a diamine.

Another object of the present invention is a process for the preparation of a previous compound, wherein said method comprising the steps of: preparing the pyridine fused to the heteroaromatic 5-membered ring; introduction of a carboxylic portion; conversion of the carboxyl portion to amine by the rearrangement of Curtius; the reaction of the group mine with a sulfonyl chloride. Another object of the present invention is a process for the preparation of a previous compound, wherein P is said method comprises the steps of: preparing the 5-membered heteroaromatic ring fused with pyridine; introduction of the sulfonyl chloride portion by nucleophilic addition; reaction of the sulfonyl chloride portion with an aniline to a sulfonamide obtained; aromatic nucleophilic substitution of chlorine with a diamine. All possible diastereomeric forms (pure enatomers, tautomers, racemic mixtures and unequal mixtures of two enantiomers) are within the scope of the invention. Said compounds can also be found as isomeric forms of double bond, cis- or trans-, E- or Z-. All isomeric forms are conteted. The compounds of the formula (I) to (XII) can be used as such or, where appropriate, pharmacologically acceptable salts thereof (acid or base addition salts). With pharmacologically acceptable addition salts as mentioned above it is meant that they comprise forms of therapeutically active non-toxic base and acid addition salts which the compounds are capable of forming. The compounds having basic properties can be converted to their pharmaceutically acceptable acid addition salts by treating the basic form with an appropriate acid. Exery acids include organic acids, such as hydrogen chloride, hydrogen bromide, hydrogen iodide, sulfuric acid; and organic acids such as acetic acid, propanoic acid, hydroxyacetic acid, lactic acid, pyruvic acid, glycolic acid, maleic acid, malonic acid, oxalic acid, benzenesulfonic acid, toluenesulfonic acid, methanesulfonic acid, trifluoroacetic acid, fumaric acid, succinic acid, malic acid, tartaric acid, citric acid, salicylic acid, p-aminosalicylic acid, pamoic acid, benzoic acid, ascorbic acid, and the like. Exery base addition salts forms are sodium, potassium, calcium salts and salts with pharmaceutically acceptable amines such as, for exa, ammonia, alkylamines, and amino acids, such as, for exa, arginine and lysine. The term "addition salts" as used herein also comprises solvates that the compounds and salts thereof are capable of forming, such as, for exa, hydrates, alcoholates and the like. For clinical use, the compounds of the invention are formulated in pharmaceutical formulations for oral, rectal, parenteral or other administration. Pharmaceutical formulations are usually prepared by mixing the active substance, or a pharmaceutically acceptable salt thereof, with conventional pharmaceutical excipients. The formulations can be further prepared by known methods such as granulation, compression, microencapsulation, spray coating, etc. The formulations can be prepared by conventional methods in the dosage form of tablets, capsules, granules, syrups, suspensions, suppositories or injections: Liquid formulations can be prepared by dissolving or suspending the active substance in water or other suitable vehicles. The tablets and granules can be coated in a conventional manner. Another object of the present invention is a prior compound for use in therapy. Another object of the present invention is a previous compound; and for the case when the rings A and B are both phenyl, P is any one of formula (a) or () substituted in position 7 on the naphthalene ring, and R3 is substituted in position on the naphthalene ring, for use in the treatment or prophylaxis of a disorder related to 5-H 6 receptor, such as obesity, type II diabetes, and / or central nervous system disorders, to achieve the reduction of body weight and body weight gain. Another object of the present invention is a prior compound for use in the treatment or prophylaxis of disorders of the central nervous system. Another object of the present invention is an anterior compound, for the case when rings A and B are both phenyl, P is any one of formula (a) or (c) substituted in position 7 on the naphthalene ring, and R3 is substituted in position 1 on the naphthalene ring, and for the case when the ring D is a pyrrole ring, P is of the formula (c) and R3 is of the formula substituted in position 3 on the pyrrole ring, for use in the treatment or prophylaxis of type II diabetes. Another object of the present invention is a previous compound, and for the case when the ring D is a pyrrole ring, P is of the formula (c) and R3 is of the formula substituted in position 3 on the pyrrole ring, for use in the treatment or prophylaxis of obesity, to achieve the reduction of body weight and weight gain. Another object of the present invention is a pharmaceutical formulation comprising a foregoing compound as an active ingredient, in combination with a pharmaceutically acceptable carrier extender.

Another object of the present invention is a pharmaceutical formulation comprising a previous compound, and for the case when rings A and B are both phenyl, P is any one of formula (a) or (c) substituted in position 7 on the ring naphthalene, and R3 is substituted in position 1 on the naphthalene ring, as an active ingredient, for use in the treatment or prophylaxis of a disorder related to the 5-HT6 receptor, such as obesity, type II diabetes, and / or disorders of the central nervous system, to achieve the reduction of corporal weight and of gain of corporal weight.

Another object of the present invention is a prior compound as an active ingredient, for use in the treatment or prophylaxis of disorders of the central nervous system. Another object of the present invention is a pharmaceutical formulation comprising a previous compound, for the case when rings A and B are both phenyl, P is any one of formula (a) or (c) substituted in position 7 on the naphthalene ring , and R3 is substituted in position 1 on the naphthalene ring, and for the case when the ring D is a pyrrole ring, P is of the formula (c) and R3 is of the formula substituted in position 3 on the pyrrole ring, as an active ingredient, for use in the treatment or prophylaxis of type II diabetes. Another object of the present invention is a pharmaceutical formulation comprising an above compound, and for the case when ring D is a pyrrole ring, P is of formula (c) and R3 is of the formula substituidp in position 3 on the pyrrole ring, as an active ingredient, for use in the treatment or prophylaxis of obesity, to achieve the reduction of body weight and weight gain. Another object of the present invention is a method for the treatment or prophylaxis of a disorder related to the 5-HT 6 receptor, such as obesity, type II diabetes, and / or central nervous system disorders, such as obesity, diabetes of type II, and / or central nervous system disorders, to achieve the reduction of body weight and body weight gain, which comprises administering to a subject (e.g., a mammal, a human, a horse, a dog, or a cat) in need of such treatment an effective amount of one or more compounds of any of the formulas described above, their salt forms or compositions including the compounds or their salt forms, and for that matter when the A rings and B are both fnyl, P is any one of formula (a) or (c) substituted in position 7 on the naphthalene ring, and R3 is substituted in position 1 on the naphthalene ring. Another object of the present invention is a method for the treatment or prophylaxis of disorders of the central nervous system, which comprises administering to a subject in need of said treatment an effective amount of one or more compounds of any of the formulas described above, their salt forms or compositions that include the compounds or their salt forms. Another object of the present invention is a method for the treatment or prophylaxis of type II diabetes, which comprises administering to a subject in need of such treatment an effective amount of one or more compounds of any of the formulas described above, their salt forms or compositions that include the compounds or their salt forms, for the case when rings A and B are both phenyl, P is any one of formula (a) or (c) substituted in position 7 on the naphthalene ring, and R3 is substituted in position 1 on the naphthalene ring, and for the case when ring D is a pyrrole ring, P is of the formula (c) and R3 is of the formula substituted in position 3 on the pyrrole ring. Another object of the present invention is a method for the treatment or prophylaxis of obesity, which comprises administering to a subject in need of said treatment an effective amount of one or more compounds of any of the formulas described above, their salt forms or compositions that include the compounds or their salt forms, and for the case when ring D is a pyrrole ring, P is of the formula (c) and R3 is of the formula substituted in position3 on the pyrrole ring. Another object of the present invention is a method for modulating the activity of the 5-HT6 receptor, which comprises administering to a subject in need thereof an effective amount of one or more compounds of any of the formulas described above, their forms of salt or compositions that include the compounds 0 your salt forms. Another object of the present invention is the use of one or more compounds of any of the formulas described above, their salt forms or compositions that include the compounds or their salt forms, and for that matter when the rings? and B are both phenyl, P is any one of formula (a) or (c) substituted in position 7 on the naphthalene ring, and R3 is substituted in position 1 on the naphthalene ring, for the manufacture of a medicament for use in the treatment or prophylaxis of a disorder related to the 5-H 6 receptor, such as obesity, type II diabetes, and / or central nervous system disorders, for achieve the reduction of body weight and weight gain. Another object of the present invention is the use of one or more compounds of any of the formulas described above, their salt forms or compositions that include the compounds or their salt forms for the manufacture of a medicament for use in the treatment or prophylaxis of disorders of the central nervous system.

Another object of the present invention is the use of one Or more compounds of any of the formulas described above, their salt forms or compositions that include the compounds or their salt forms, for the case when ring A and B are both phenyl, P is any one of formula (a) or (c) substituted in position 7 on the naphthalene ring, and R3 is substituted in position 1 on the naphthalene ring, and for the case when ring D is a pyrrole ring, P is of the formula (c) and R3 is of the formula substituted in position 3 on the pyrrole ring, for the manufacture of a medicament for use in the treatment or prophylaxis of type II diabetes.

Another object of the present invention is the use of one or more compounds of any of the formulas described above, their salt forms or compositions including the compounds or their salt forms, and for that matter when ring D is a pyrrole ring , P is of the formula '(c) and R3 is of the formula . substituted in position 3 on the pyrrole ring, for the manufacture of a medicament for use in the treatment or prophylaxis of obesity, to achieve the reduction of body weight and the gain of body weight. The methods outlined herein may also include the stage of identifying that the subject is in need of treatment of obesity, of type II diabetes, or of disorders of the central nervous system, or in need of reducing body weight and of gaining weight. body The invention also further concerns the cosmetic use of one or more compounds of any of the formulas described above, to cause weight loss, as well as cosmetic compositions containing said compounds. Still further, the invention concerns a non-therapeutic method for improving the body appearance of a mammal, including a human, which method comprises orally administering to the mammal one or more compounds of any of the formulas described above. "An effective amount" refers to an amount of a compound that confers a therapeutic effect on the treated subject. The therapeutic effect can be objective (ie, measurable by some test or macrador) or subjective (that is, the subject gives an indication of or feeling an effect). For clinical use, the compounds of the invention are formulated in pharmaceutical formulations for oral, rectal, parenteral or other administration. Usually the amount of active compounds is between 0.1-95% by weight of the preparation, preferably between 0.2-20% by weight in preparations for parenteral use and preferably between 1 and 50% by weight in preparations for oral administration. The typical daily dose of the active substance varies over a wide range and will depend on several factors such as, for example, the individual requirement of each patient and the route of administration. In general, oral and parenteral dosages will be in the range of 5 to 1000 mg per day of active substance, preferably 50 to 150 mg per day. Processes for the Preparation In a further aspect the invention concerns methods for making compounds of any of the formulas herein which comprise reacting any one or more of the compounds of the formulas delineated herein, including any process delineated herein . The compounds of the above formulas can be prepared by, or in analogy to, conventional methods, and especially in accordance with or in analogy with the following methods. The chemicals used in the aforementioned synthetic route may include, for example, solvents, reatives, catalysts, reactive protecting groups. The methods described above may additionally include steps, either before or after the steps specifically described herein, to add or remove protecting groups in order to finally allow the synthesis of the compounds of any of the formulas described above, their forms of salt or compositions that include the compounds or their salt forms. In addition, various synthetic steps can be carried out in an alternating sequence in order to give the desired compounds. Synthetic chemical transformations and protective group methodologies (protection and deprotection) useful in synthesizing the applicable compounds are known in the art and include, for example, those described in R. Larock, Comprehensive Organic Transformations, VCH Publishers (1989); T. W. Greene and P.G.M. Wuts, Protective Groups in Organic Synthesis, 2a. Ed. John iley & Sons (1991); L. Fieser and M. Fieser's Reagents of Organic Synthesis, John Wiley & Sons (1994); and L. Paquette, ed. Encyclopedia of Reagents for Organic Synthesis, John Wiley & Sons (1995) and subsequent editions of the same. The following examples were constructed as merely illustrative, and non-limiting of the remainder of the description in any way. Without further elaboration it is believed that one skilled in the art can, based on. the present disclosure, use the present invention to its fullest extent. All publications cited entirely herein are incorporated herein by reference. Methods The 1H spectra of nuclear magnetic resonance (NMR) and 13C NMR were recorded in a Bruker Advance Bruker Advance spectrophotometer at 400.1 and 100.6 MHz respectively. All spectra were recorded using solvent residula or 'tetramethylsilane (TMS) as internal standards. The IR spectra were recorded on a Perkin-Elmer Spectrum 1000 FT-IR spectrophotometer. Mass spectrometry (MS) spectra were obtained by ionic nebulization on a Perkin-Elmer API 150EX mass spectrometer. The precise measurements were made in a dual-probe LCM Micormass. Preparative MS / HPLC were performed on a Waters / Micormass Platform ZQ system equipped with a column for the? System: ACE 5 C8 (19 x 50 mine), eluents: MilliQ water, MeCN and MilliQ / MeCN / 0.1% TFA and columan for system B: Xterra MS C18, of 5 um (19 x 50 mm), eluents: water MilliQ, MeCN and NH4HC03 (100 mM). Analytical HPLC was performed on Agxlent 1100 column: ACE 3 C8 (system A) or column: YMC-Pack (system B), eluents: MilliQ / 0.1% TFA and MeCN. The elemental analyzes were carried out on a Vario El instrument. Preparative flash chromatography on Merck 60 silica gel (230-400 mesh) was carried out.

Table 1 EXAMPLE R * R * 1 6-Benzenesulfanyl-4-piperazin-1-quinoline 9 0 Hydrochloride 2 Hydrochloride of 6- [. { 2- fluorophenyl) suffoni!] - 4- piperazin-1-ylquinoline 0 3 6- (1- Naphue-sulfonyl) -4- piperazin-1-ylquinoline hydrochloride 0 4 6 - [(3, 4-Dichlorophenyl) Cl sulfonyl] -4- piperazin-1-ylquinoline hydrochloride 0 5 6- [(3,5-Dimethyl-phenyl) sulfonyl] -4- piperazin-1-ylquinoline hydrochloride and 0 Chlorohydrate 1-chloro-5-methylphenylsulfonyl] -4- piperazin- 1 -quinoline 0 7 6- [(4-chlorofsnyl) Cl sulfonyl] -4- piperazin-1-ylquinoline hydrochloride 0 8 6 - [(2- rneul, 4- tert-buyl-phene) sulfonyl] -4- piperazin-1-ylquinoline hydrochloride 0 9 Hydrochloride 6- [. { 3, -dimethylphenyl) sulfonyl] -4- piperazin-1-ylquinoline 0 10 6- [(2,3-Dichlorophenyl) sulfonyl] -4- piperazin-1-ylquinoline hydrochloride 0 11 6- [(4-tert-Butylphenyl) sulfonyl] -4- piperazin-1-ylquinoline hydrochloride 0 Reaction Scheme 1 Legends of Reaction Scheme 1: i) hydrogen gas, Pd / C, methanol; ii) sodium nitrite, sulfuric acid, various thiols (Rj.-SH), 3; iii) meta-chloroperoxybenzoxc acid (m-CPBA), dichloromethane (CH2C12), overnight; iv) phosphorus oxychloride (P0C13), acetonitrile (C¾CN), 80 ° C, 2 h; v) cyclic aliphatic amines (R2), 80 ° C, CH3CN; vi) HC1 in diethyl ether.

Methods The assigned structures were confirmed by means of standard spectroscopic methods and elemental analysis and / or high resolution MS. The NMR spectrum was obtained in spectrometers 500 MHz Brucker or 270 MHz JEOL at 25 ° C, and chemical shift values reported as parts per million (5). The MS spectra were acquired in a Separation Module (Waters) with a Platform LCZ (Micromass). Flash chromatography was carried out on silica gel 60 (Merck or LiChroprep RP-18 (merck). HPLC analyzes were achieved in an HP Series 1100, with a GROM-SIL 100 ODS-0 AB column, 4.6 x 50 itim. HPLC purifications were performed on the HPLC / Mass Preparative system using YMC Combi prep ODS-AQ column, 56 x 20 mm, Gilson pumps, Dynamax UV-1 detector and Finnigan Mass detector. The eluents used were H20 and CH3CN, both with 0.1% TFA The purity of the compounds was determined by mHPLC Elemental analysis was performed in the Structural Chemistry Department, Biovitrium AB, Stockholm.Fusion points, when they were given, were obtained in a Büchi effusion point equipment or a Gallenkamp and were not corrected INTERMEDIARY 1 Synthesis of 6-Amino-quinoline A suspension of 6-nitro-quinoline (8.7 g, 5 mmol), palladium on carbon (10%) (0.1 g) in methanol (0.2 1) was hydrogenated at room temperature for 24 hours with stirring. filtered and the solvent was evaporated to yield a yellow solid. Crystallization of the ethyl acetate afforded the pure title compound as a pale yellow solid (3.3 g, 46%). MS m / z: 145 [M + H] +. ¾ NR (270 MHz, CHCl3-ds) d ppm 3.89 (s, 2H) 6.87 (d, J = 2.64 Hz, 1H) 7.14 (dd, J = 8.97, 2.64 Hx, 1H) 7.25 (dd, J = 8.44, 4.22 Hz, 1H) 7.88 (dd, J = 7.92, 1.58, 1H) 7.90 (d, J = 8.97 Hz, 1H) 8.63 (dd, J = 4.22, 1.58 Hz, 1H). INTERMEDIARY 2 Synthesis of 6-phenylsulfanyl-quinoline A solution of sodium nitrite (1 g, 14 mmol) in water (6 ml) was added slowly to a stirred solution of 6-amino-quinoline (1.44 g, 10 mmol) in acid sulfuric (50%) (8 ml). The temperature was kept below 5 ° C during the addition. The reaction mixture was poured into a solution of potassium hydroxide (9 g, 16 mmol) and thiophenol (1 mL, 9 mmol) in water (30 mL). The reaction mixture was refluxed for 3 hours, cooled and extracted with diethyl ether. The insoluble material was removed by filtration. During filtration most of the material was trapped in the solid phase. The filtrate was evaporated and the residue was purified by column chromatography (Si02, ethyl acetate rhexane, 1: 2) to yield a colorless oil (100 mg, PS at 4%: the low yield is due to the loss of material during the filtration process). MS m / z: 238 [M + H] +. ¾ NMR (270 MHz, CD3C1) d ppm 7.34 (m, 4H) 7.42 [m, 2H) 7.57 (dd, J = 8.97, 2.11 Hz, 1H) 7.67 (d, J = 2.11 Hz, 1H) 7.99 (m, 2H) 8.44 (dd, J = 4.22, 1.58 Hz, 1H). INTERMEDIARY 3 Synthesis of 6-benzenesulfonylquinoline 1-oxide A solution of m-chlorobenzoic acid (1 g, 5.8 mmol) in DCM (10 mL) was added to a stirred solution of 6-phenylsulfanyl-quinoline (0.25 g, 1 mmoles) and NaHCO3 (0.5 g) in DCM (10 mL) The reaction was allowed to stir overnight, washed with water, NaHCC and evaporated, trituration of the residue in diethyl ether gave the pure title product as a solid. slightly yellow (0.14 g, 30%) MS m / z: 287 [M + H +] INTERMEDIARY 4 Synthesis of 6-benzenesulfonyl-4-chloro-quinoline A solution of 1-oxide of 6-benzenesulfonylquinoline was heated ( 135 mg, 0.47 mmol) in POC13 (4 mL) at 90 ° C for 2 hours, after which the solution was poured onto ice, ammonium hydroxide was added and extracted with DCM The organic phase was dried (Na2SO4) The volatile materials were evaporated and the residue was purified by column chromatography (S1O2, ethyl acetate: petroleum ether, 1: 1). to produce a white solid (39 mg, 27%). MS m / z: 305 [M + H +]. EXAMPLE 1 Synthesis of 6- benzenesulfonyl-4-piperazin-1-yl-quinoline hydrochloride A solution of 6-benzenesulfonyl-4-chloro-quinoline (35 mg, 0.11 mmol) and piperazine was heated at 80 ° C overnight. (0.5 g, 2.5 mmol) in acetonitrile (2 ml). The mixture was extracted with toluene and water. The organic phase was purified by chromatography on silica gel eluted with CHC13 saturated with N¾ (gas). The pure product was dissolved in ethyl acetate and HC1 (gas) in diethyl ether was added. The resulting oily residue was dissolved in methanol and ethyl acetate and evaporated to yield a white solid (24 mg), 77%). MS m / z: 354 [M + H] +. X H MR (270 MHz, CH 3 OH-D 4) d ppm 3.52 (m, 4 H) 4.13 (m, 4 H) 7.36 (d, J = 7.18 Hz, 1 H) 7.57 (m, 3 H) 8.01 (m, J = 12.25, 8.54 Hz, 3H) 8.28 (d, J = 8.91 Hz, 1H) 8.63 (d, J = 6.68 Hz, 1H) 8.69 (s, 1H).

Reaction Scheme 2 2a, n = 0 2b, n = 1 Legends for Reaction Scheme 2: i) NatBuO, Pd (PPh3) 4, n-BuGH, diamines protected with BOC; ii) tert-butyl piperazin-1-carboxylate or tert-butyl-1,4-diazepane-1-carboxylate or K2C03 / DMSO, thiols; iv) TFA, H202, NaOH; iv) HC1. Method A Preparation of thiol derivatives 4- (6-bromoquinolin-4-yl) -1,4-diazepane-1-tert-butyl carboxylate (0.5 g, 1.23 mmol) was mixed with the thiol (1 equiv.), NaOtBu (2 equiv.), Pd (PPh3) 4 (0.05 equiv.) And n-BuOH (5 ml) in a reaction tube. N2 (g) was bubbled through the mixture for 30 minutes. The reaction mixture was heated at 120 ° C overnight. The precipitate was filtered and the reaction mixture concentrated in vacuo. The residue was dissolved in EtOAc and washed with H20, dried (MgSO4) and evaporated. Purification by flash chromatography using DCMrMeOH 98: 2 as eluent afforded the title product which was used in the next step without further purification. Method B Oxidation of thiol derivatives to sulfone derivatives The appropriate thiophenol derivatives are dissolved in TFA (5 ml) and stirred for 15 minutes at room temperature. H2O2 (2 mL) was added and the reaction was allowed to stir overnight. The reaction mixtures were evaporated and the residues were partitioned between diethyl ether and water. The layers were separated and the aqueous layer was extracted with diethyl ether and basified by addition of 1 M NaOH. Extraction with DCM, drying with MgSO4 and evaporation gave the free bases of the products, which were dissolved in MeOH, excess HCl / ether (2 M) was added and the solvent was evaporated. The residues were purified on preparative MS / HPLC (Xterra MS C18 column, 5 uM) using a gradient of 10-40% MeCN-water (containing 0.1% HOAc) for 10 minutes. The spiked fractions were combined and elophilized. The residues were dissolved in MeOH and treated with excess HCl / ether (2 M). After evaporation of the solvent, a solid was obtained and triturated with diethyl ether to give the desired products as hydrochloride salts. INTERMEDIARY 5- 4- (6-bromoquinolin-4-yl) piperazine-1-carboxylate of tert-butyl 6-bromo-4-chloroquinoline (5.0 g, 20.6 mmol), tert-butyl-1-piperazine (4.1 g, 22 immoles), triethylamine (3 mL, 22 mmol) and DMSO (20 mL) and were heated overnight in an oil bath at 100 ° C. The reaction was cooled and diluted with diethyl ether and washed with water (5 x), dried (MgSO 4) and evaporated. The residue was filtered through a short column of silica (2.5-5%) MeOH in CH2C12 and evaporated. Product, 8.02 g (97). Brown liquid 98% by HPLC, RT = 3.01 (Al System, 10-97% MeCM for 3 minutes). XH NMR (400 MHz, CDC13) d ppm 1.52 (s, 9 H) 3.12-3.17 (m, 4 H) 3.69-3.75 (m, 4 H) 6.86 (d, J = 5.0 Hz, 1 H) 7.72 (dd) , J = 9.0, 2.26 Hz, 1 H) 7.92 (d, J = 8.8 Hz, 1 H) 8.14 (d, J = 2.3 Hz, 1 H) 8.73 (d, J = 5.0 Hz, 1 H). MS (ESI +) for Ci8H22Br 302 m / z 392.2 (M + H) +. EXAMPLE 2 6 - [(2-Fluiorophenyl) sulfonyl] -4-piperazin-1-ylquinoline hydrochloride A total amount of 2.25 mmol of the appropriate thiophenol was used and the reaction was continued with 8 hours. The reaction step was completed after 24 hours at room temperature. Purification by column chromatography on silica gel 10-20% MeOH in DCM gave the free amine which was further purified by preparative HPLC. Product, 15 mg (4%), yellow solid. 95 ¾ by HPLC, RT = 2.33 (Al System, 10 - 97% MeCN during 3 min). 1 H NMR (400 MHz, DMSO-d 6) d ppm 3.30 - 3.42 (m, 4 H) 3.51 - 3.62 (m, 4 H) 7.28 (d, J = 5.27 Hz, 1 H) 7.42 (dd, J = 10.29, 8.78 Hz, 1 H) 7.52 (t, J = 7.28 Hz, 1 H) 7.77-7.84 (m, 1 8.04-8.21 (m, 3 H) 8.62 (s, 1 H) 8.87 (d, J = 5.27 Hz, 1 H) 9.82 (br s, 2 H) MS (ESI +) CigHi8FN302S m / z 372.0 (M + H) +. HRMS for C19H18SFN302S: calculated, 371.1104; found, 371.1102. EXAMPLE 3 6- (1- Naphthylsulfonyl) -4 Hydrochloride piperazin-1-ylquinoline A total amount of 2.25 mmol of the appropriate thiophenol was used and the reaction was continued for 8 hours The reaction step was completed after 24 hours at room temperature Purification by gel column chromatography silica 10-20% MeOH in DCM gave the free amine which was converted to the hydrochloride salt Product, 14 mg (4%), gray solid 95% by HPLC, RT = 2.54 (Al System, 10-97% MeCN for 3 min.) ½ NMR (400 MHz, DMSO-d5) d ppm 3.33 (s, 4 H) 4.06 (s, 4 H) 7.38 (d, J = 6.78 Hz, 1 H) 7.65 (d, J = 7.53 Hz, 1 H) 7.69-7.75 (m, 1 H) 7.82 (t, J = 7.78 Hz, 1 H) 8.12 ( d, J = 8.03 Hz, 1 H) 8.21-8.30 (m, 2 H) 8.38 (d, J = 8.03 Hz, 1 H) 8.56 (t, J = 8.53 Hz, 2 H) 8.74-8.79 (m, 2 H) 10.05 (s, 2 H). MS (ESI +) for C23H21 302S m / z 404.4 (M + H +) HRMS for C23H21 3O2S: calculated, 403.1354; found, 403.1365. EXAMPLE 4 6- [(3,4-Dichlorophenyl) sulfonyl] -4- piperazin-1-ylquinoline hydrochloride A total amount of 2.25 mmol of the appropriate thiophenol was used and the reaction was continued for 8 hours. The reaction step was completed after 24 hours at room temperature. Purification by column chromatography on silica gel 10-20% MeOH in DCM gave the free amine which was converted to the hydrochloride salt to give a yellow solid. Product, 15 mg (3%), yellow solid. aH MR (400 Mez, DMSO- d6) d ppm 3.35-3.41 (m, 4 H) 4.06-4.15 '(m, 4 H) 7.40 (d, J = 6.78 Hz, 1 H) 7.93 (d, ~ J = 8.53 Hz, 1 H) 8.04 (dd, J = 8.53, 2.01 Hz, 1 H) 8.27 (d, J = 9.03 Hz, 1 H) 8.32 (d, J = 2.01 Hz, 1 H) 8.36-8.42 ( m, 1 H) 8.73 (d, J = 1.51 Hz, 1 H) 8.82 (d, J = 6.53 Hz, 1 H) 9.86 (s, 2 H). MS (ESI +) for CisHa7Cl2 302S m / z 422.2 (M + H +). HRMS for CigHnCIzNsOzS: calculated, 421.0419; found, 421.0422. HPLC 95%, RT = 2.69 (System Al, 10-97% MeCN for 3 min) EXAMPLE 5 Hydrochloride of 6- [(3,5-dimethylphenyl) sulfonyl] -4-piperazin-1-ylquinoline The oxidation step was completed after 2 hours at room temperature. Purification by column chromatography on silica gel 10-20% MeOH in DCM gave the free amine, which was converted to the hydrochloride salt to give a gray solid. Product 0.007 g (2%). Solid yellow. 90% by HPLC, RT = 2.57 (Al System, 10-97% MeCN for 3 minutes). MS (ESI +) for C21H23FN3O2S m / z 382.2. HRMS for C 21 H 23 FN 3 O 2 S: calculated, 381.1511; found, 381.1521. EXAMPLE 6 6- [(2-Chloro-6-methylphenyl) sulfonyl] -4- piperazin-1-ylquinoline hydrochloride A total amount of 2.25 mmol of the appropriate thiophenol was used and the reaction was continued for 8 hours. Additional H 2 O 2 (1 mL) was added and the reaction mixture was stirred at 50 ° C for a further 48 hours. Purification by column chromatography on silica gel 10-20% MeOH in DCM gave the free amine which was converted to the hydrochloride salt. Product, - 33 mg (7.5%). White solid. 1 H NMR (400 MHz, DMSO-ds) d ppm 2.13 (s, 3 H) 2.98 (s, 4 H) 3.72 (s, 4 H) 7.06 (d, J = 6.78 Hz, 1 H) 7.14 (dd, J = 11.54, 8.03 Hz, 2 H) 7.23 (t, J = 7.78 Hz, 1 H) 7.89 (d, J = 8.78 Hz, 1 H) 7.94-8.00 (m, 1 H) 8.24 (s, 1 H) 8.45 (d, J = 6.78 Hz, 1 H) 9.68 (s, 2 H). MS (ESI +) for C20H20CIN3O2S m / z 402.2 (M + H). HRMS for C20H20CIN3O2S: calculated, 4O1.965 found, 401.967. HPLC 95%, RT = 2.55 (System Al, 10-97% MeCN for 3 min). EXAMPLE 7 Hydrochloride 6- [. { 4-chlorophenyl) sulfonyl] -4-piperazin-1-ylquinoline A total amount of 2.25 mmol, of the appropriate thiophenol was used and the reaction was prolonged with 8 hours. The reaction step was completed after 24 hours at room temperature. Purification by column chromatography on silica gel 10-20% MeOH in DCM gave the free amine which was converted to the hydrochloride salt. Product, 14 mg (3%). Solid yellow. 95% by HPLC, RT = 2.66 (Al System, 10-97% MeCN for 3 min). MS (ESI +) for Ci9H13ClN302S m / z 388.2 (M + H +). HRMS for Ci9H18ClN302S: calculated, 387.0808; found, 387.0821. EXAMPLE 8 6- [(2-Methyl, 4- tert-butylphenyl) sulfonyl] -4- piperazin-1-ylquinoline hydrochloride The oxidation was complete after 2 hours at room temperature. Purification by column chromatography on silica gel 10-20% MeOH in DCM gave the free amine, which was converted to the hydrochloride salt to give a gray solid. Product, 17 mg (4%). 95% by HPLC, RT = 2.81 (Al System, 10-97% MeCN for 3 minutes). MS (ESI +) for C24H29N302S m / z 424.2 (M + H +). HRMS for C24H29 302S: calculated, 423.1980; found, 423.1969. EXAMPLE 9 6- [(3, 4-Dimethyl enyl) sulfonyl] -4-piperazin-1-ylquinoline hydrochloride The oxidation step was complete after 2 hours at room temperature. Purification by column chromatography on silica gel 10-20% MeOH in DCM gave the free amine which was converted to the hydrochloride salt. Product, 33 mg (8%). Solid yellow. ¾ NMR (400 MHz, DMS0-d6) d ppm 2.27 (d.J = 6.27 Hz, 6 H) 3.34 (s, 4 H) 4.12 (s, 4 H) 7.39 (dd, J = 7.40, 2.13 Hz, 2 H) 7.75 (d, J = 7.78 Hz, 1 H), 7.81 (s, 1 H) 8.32 (s, 2 H) 8.61 (s, 1 H) 8.78 (d, J = 6.78 liz, 1H) 10.18 (s, 2 H). MS (ESI +) for C21H23N302S m / z 382.2 (M + H +). HRMS for C2iH23N302S: calculated, 381.1511; found, 381.1519. HPLC 95%, RT = 2.54 (System Al, 10-97% MeCN for 3 min). EXAMPLE 10 6- [(2, 3-Dichlorophenyl) sulfonyl] -4-piperazin-1-ylquinoline hydrochloride A total amount of 2.25 mmol of the appropriate thiophenol was used and the reaction was continued for 8 hours. The reaction step was completed after 24 hours at room temperature. Purification by column chromatography on silica gel 10-20% MeOH in DCM gave the free amine which was converted to the hydrochloride salt.

Product, 15 mg (3%). Solid yellow. ½ NMR (400 MHz, DMSO-d5) d ppm 3.36 (m, 4 H) 4.10 (m, 4 H) 7.42 (d, J = 6.78 Hz, 1 H) 7.75 (t, J = 8.03 Hz, 1 H) 8.07 (d, J = 8.03 Hz, 1 H) 8.24 (d, J = 9.04 Hz, 1 H) 8.33 (dd, J = 13.93, 8.41 Hz, 2 H) 8.70 (s, 1 H) 8.82 (d, J = 6.78 Hz, 1 H) 10.00 (s, 2 H). MS (ESI +): for C19Hi7Ci2N3028 m / z 422.2 (M + H +). HRMS for: calculated, 421.0419; found, 421.0408. HPLC 95%, RT = 2.50 (System Al, 10-97% MeCN for 3 min). EXAMPLE 11 6- [(4-tert-Butylphenyl) sulfonyl] -4-piperazin-1-ylquinoline hydrochloride 4- was dissolved. { 6- [(4- tert -butylphenyl) thio] quinolin-4-yl} piperazin-1-tert-butyl carboxylate (0.60 g, 1.3 mmol) in TFA (12 mL) and stirred for 30 minutes before adding H202 (0.65 mL, 6.3 mmol). The mixture was stirred for 2 hours and water (5 ml) was added. The mixture was evaporated and the residue was taken up in water and washed with diethyl ether (2 x). The aqueous phase was adjusted to pH 10 with 1 N NaOH and the mixture was extracted with CH2C12 (2 x), dried (MgSO4) and evaporated. The residue was diluted with CH2C12 and 1.3 ml of 2N HCl in diethyl ether was added under vigorous stirring and the mixture was evaporated and washed with diethyl ether (2 x) and dried. Product: 0.40 g (69%). Solid gray. 95% by HPLC, RT = 2.77 (Al System, 10-97% MeCN for 3 minutes). ¾ NMR (400 MHz, DMSO-d6) d ppm 1.23 (s, 9 H, 3.38 (s, 4 H) 4.08 (s, 4 H) 7.39 (d, J = 7. (Hz, 1 H) 7.65 (d , J = 8.53 Hz, 2 H) 7.96 (d, J = 8.53 Hz, 2 H) 8.25 (d, J = 8.78 Hz, 1 H) 8.30 8.36 (m, 1 H) 8.66 (d, J = 1.76 Hz , 1 H) 8.81 (d, J = 7.03 Hz, 1 H) 9.85 (br.s, 2 H), MS (ESI +) for C23H27N3O2S m / z 410.4 (M + H +) EXAMPLE 12 Hydrochloride of 6- [( 4-isopropylphenyl) sulfonyl] -4-piperazin-1-ylquinoline 4-isopropylthiophenol (0.152 g, 1.0 mmol) was added dropwise to a suspension of 4- (6-bromo-quinolin-4-yl) -piperazine-1. - tert-butyl carboxylate (0.2 g, 0.51 mmol), sodium t-butoxide (0.192 g, 2.0 mmol) and Pd [P (Ph) 3] 4 (0.030 g, 0.025 mmol) in ethanol (3 ml) a 90 ° C and the mixture was stirred for 18 h.The mixture was diluted with THF and filtered through a plug of silica and evaporated.The crude product was dissolved in TFA (5 ml) and stirred for 15 minutes before to add H2O2 to 30% (1 mL) The mixture was stirred for 2 hours and evaporated. The mixture was extracted with water and washed with CH2Cl2 (2 x) and 2N NaOH was added until the pH reached 10 and the mixture was extracted with CH2C12 (3x), dried (MgSO4) and evaporated. The crude product was purified by preparative HPLC 5-95 of water / acetonitrile collecting in m / z 395.2. After evaporation in vacuo the free amine was dissolved in CH 2 Cl 2 and excess HC1 diethyl ether was added and the mixture was evaporated. Product, 0.015 g (7%). ¾ NMR (400 MHz, DMS0-ds) d ppm 1.17 (d, J = 7.03 Hz, 6 H) 2.90-3.02 (m, 1 H) 3.34-3.42 (m, 4 H) 4.03-4.12 (m, 4 H) ) 7.39 (J = 6.78 Hz, 1 H) 7.51 (d, J = 8.28 Hz, 2 H) 7.96 (d, J = 8.53 Hz, 2 H) 8.26 (d, J = 9.03 Hz, 1 H) 8.29-8.36 (m, 1 H) 8.66 (s, 1 H) 8.80 (d, J = 6.78 Hz, 1 H) 9.85-9.97 (m, 2 H). HPLC, 95%, RT = 2.65 (Al System, 10-97% MeCN for 3 min). EXAMPLE 13 4- Piperazin-1-yl-6-Hydrochloride. { [4- (trifluoromethyl) phenyl] sulfonyl} quinoline 4- trifluoromethylthiophenol (0.178 g) was added, 1.0 mmol) dropwise to a suspension of 4- (6-bromo-quinolin-4-yl) -piperazin-1-tert-butyl carboxylate (0.2 g, 0.51 mmol), sodium t-butoxide (0.192 g). , 2.0 mmol) and Pd [P (Ph) 3] 4 (0.030 g, 0.025 mmol) in ethanol (3 mL) at 90 ° C and the mixture was stirred for 18 hours. The mixture was diluted with THF and filtered through a plug of silica and evaporated. The crude product was dissolved in TFA (5 mL) and stirred for 15 minutes before adding 30% H202 (1 mL). The mixture was stirred for 2 hours and evaporated. The residue was dissolved in water and washed with CH2C12 (2 x) and 2N NaOH was added until the pH reached 10 and the mixture was extracted with CH2C12 (3x), dried (MgSO4) and evaporated. The crude product was purified by preparative HPLC 5-95 of water / acetonitrile colecand on m / z 421.1. After evaporation the free amine was dissolved in C¾Cl 2 and excess HCl in diethyl ether was added and the mixture was evaporated. Product, 0.024 g (10%). ¾ MR (400 MHz, DMSO-d6) d ppm 3.33-3.40 (m, 4 H) 4.13-4.21 (m, 4 H) 7.42 (d, J = 7.03 Hz, 1 H) 8.02 (d, J = 8.53 Hz , 2 H) 8.25-8.35 (m, 3 H) 8.37-8.53 (m, 1 H) 8.76 (d, J = 1.76 Hz, 1 H) 8.80 (d, J = 7.03 Hz, 1 H) 9.95-10.05 ( m, 2 H). Yellow oil HPLC, 95%, RT = 2.66 (Al System, 10-97% MeCN for 3 min). INTERMEDIARY 6 4- (6- bromoquinolin-4-yl) -1,4-diazepane-1-carboxylic acid tert-butyl ester 6-bromo-4-chloroquinoline (3.5 g, 14.5 mmol) was reacted with 1,4-diazepam - 1-tert-butyl carboxylate (3.7 g, 18.8 mmol) and K2CO3 (4 g, 29 mmol) in DMSO at 100 ° C overnight. After cooling the mixture was poured into water and extracted with DCM. The organic layer was washed with water, dried (MgSO) and evaporated. The residue was purified by flash chromatography using a gradient of EtOAcchexane 1: 1 to 2: 1 yielding 2.1 g (36%) of yellow oil.

¾ NMR (400 MHz, CDC13) d ppm 1.47 (d, J = 5.5 Hz, 9 H) 2.08-2.16 (m, 2 H) 3.35-3.44 (m, 4 H) 3.60-3-73 (m, 4 H ) 6.87 (d, J = 5.5 Hz, 1 H) 7.69 (d, J = 9.0, 2.0 Hz, 1 H) 7.88 (d, J = 8.5 Hz, 1 H) 8.16 (s, 1 H) 8.65 (d, J = 5.0 Hz, 1 H). MS (ESI +) for Ci9H24BrN302 m / z 406.4 (M + H +). HRMS (El) calculated for C19H24BrN3: 405.1052, found, 405.1045. INTEEMEDIARY 7 4-. { 3- [(4- tert -butylphenyl) thio] quinolin-5-yl} -1,4-diazepane-1-tert-butyl carboxylate (General Method A) The compound was prepared from 4- (6-bromoquinolin-4-yl) -1,4-diazepane-1-tert-butyl carboxylate ( 0.5 g, 1.23 immoles) and p-tert-butylbenzothiol (0.2 g, 1.23 immoles). Product: 0.27 g (44%) of the title compound. 89% by HPLC, RT = 3.76 minutes (5-99% MeCN containing 0.1% TFA for 3 minutes). INTERMEDIARY 8 4-. { 3- [(4-isopropylphenyl) thio] quinolin-5-yl} -1,4-diazepane-1-tert-butyl carboxylate The compound was prepared from 4- (6-bromoguinolin-4-yl) -1,4-diazepane-1-tert-butyl carboxylate (0.5 g, 1.23 mmoles). ) and 4-isopropylbenzothiol (0.19 g, 1.23 immoles). Product: 0.27 g (46%) of the title compound which was used in the next step without further purification. 89 ¾ by HPLC, RT = 3.67 minutes (5-99% MeCN containing 1% TFA for 3 minutes); MS (ESI +) for C28H35 3O2S m / z 478.2 (M + H +). EXAMPLE 14 6- [(4-tert-Butylphenyl) sulfonyl] -4- (1, 4-diazepan-1-yl) quinoline hydrochloride (General Method B) The compound was synthesized from 4. { 3- [(4-tert-butylphenyl) thio] quinolin-5-yl} - 1, 4- tert-butyl diazepane-1-carboxylate (0.27 g, 0.55 mmol). Product: 20 mg (8%) of the title compound; aH NMR (270 MHz, DMSO-d6) d ppm 1.25 (s, 9 H) 2.31 (br s, 2 H) 3.25 (br s, 2 H) 3.49 (br s, 2 H) 4.11 br s, 2 H 4.26 (br s, 2 H) 7.16 (d, J = 7.1 Hz, 1 H) 7.65 (d, J = 8.2 Hz, 2 H) 7.94 (d, J = 8.2 Hz, 2 H) 8.19 (d, J = 8.7 Hz, 1 H) 8.26 (d, J = 8.7 1 H) 8.62 (d, J = 6.3 Hz, 1 H) 8.75 (s, 1 H) 9.65 (br s, 2 H); MS (ESI +) for C 24 H 29 N 3 O 2 S m / z 424.2 (M + H) +. HPLC, 93%, RT: 2.79 rain (5-99% MeCN during 3 rain). EXAMPLE 15 4- (1, 4-diazepan-1-yl) -6- [(4-isopropylphenyl) sulfonyl] quinoline hydrochloride (General Method B) The compound was prepared from 4. { 3- [(4-isopropylphenyl) thio] quinolin-5-yl} - 1, 4- tert-butyl diazepane-1-carboxylate (0.27 g, 0.57 mmol).

Product: 15 mg (6%) of the title compound; 1 H NMR (270 MHz, DMS0-d 6) d ppm 1.16 (d, J = 6.9 Hz, 6 H) 2.31 (br s, 2 H) 2.96 (m, 1 H) 3.25 (rs, 2 H) 3.49 (br s , 2 H) 4.11 (br s, 2 H) 4.26 (br s, 2 H) 7.16 (d, J = 6.9 Hz, 1 H) 7.51 (d, J = 8.2 Hz, 2 H) 7.94 (d, J = 8.2 Hz, 2 H) 8.18 (d, J = 8.7 Hz, 1 H) 8.30 (d, J = 8.4 Hz, 1 H) 8.62 (d, J = 6.1 Hz, 1 H) 8.75 (s, 1 H) 9.62 (br s, 2 H); MS (ESI +) for C 23 H 27 N 3 O 2 S m / z 410.4 (M + H +). HPLC 93%, RT: 2.70 min (5-99% MeCN for 3 min).

Table 2 Reaction Scheme 3 Legends of Reaction Scheme 3: i) P0C13; ii) K2C03, DMF, diamines-BOC; iii) Na-t-BuO, thiophenols, Pd (PPh3) 4; n-BuOH; iv) TFA, H202; v) HC1 in diethyl ether.

INTERMEDIARY 9 7- Bromo-1-chloroisoquinoline To phosphorus oxychloride (46.6 ml, 0.5 mol) at room temperature, 7-bromo-1-hydroxyquinoline (11.2 g, 0.05 mol) was added in portions. The mixture was heated at 100 ° C for 90 minutes with rapid stirring. With cooling to room temperature, the mixture was poured cautiously onto ice / water (200 ml). The drop drop of aqueous ammonia raised the pH to 8 and the resulting precipitate was collected by filtration, washed with cold water. The solid was dried under reduced vacuum at 45 ° C for 12 hours. 13.86 g (115 S). Solid beige isolated. XH NMR (DMS0-ds) d 8.4 (s, 1 H), 8.34-8.38 (d, J = 6 Hz, 1 H), 8.03-8.07 (m, 2 and 7.91-7.96 (d, J = 6 Hz, 1 H); HPLC: 96%; LCMS: 242,244,246, Nucleophilic displacement of chlorine INTERMEDIARY 10 4- (7- bromo-isoquinoline-1-yl) -piperazine-1-carboxylic acid tert-butyl ester To a suspension of 7- bromo-l-chloroisoquinoline (3.14 g, 1.3 mmol) in DMSO (20 mL) at room temperature added either tert-butyl (BOC) piperazine carboxylic acid (7.23 g), 38.8 miaoles). The mixture was heated at 110 ° C for 24 hours. With cooling, the mixture was poured onto ice / water (50 ml) and extracted with ethyl acetate (3 x 50 ml). The combined organic phases were washed with water (50 ml) and brine (50 ml). Before drying over anhydrous sodium sulfate. Removal of the solvent under reduced pressure gave crude product. Purification was effected by applying the crude material to a silica plug in a filter funnel and eluting with heptane / ethyl acetate (2: 1) and giving 2.73 g (54%). Yellow oil 1H NR (CDC13) d 8.20-8.22 (? A, 1 H), 8.13-8.1 8 (d, J = 6 Hz, 1 H), 7.65-7-71 [, J = 12, 3 Hz, 1 H) , 7.59-7.65 (d, J = 12 Hz, 1 H), 7.21-7.25 (H, 1 H), 3.64-3.73 (m, 4H) 7.27-7.36 (m, 4 H), 1.49 (s, 9 H ); LCMS: 392,394,395. INTERMEDIARY 11 4- (7-bromo-isoquinolin-1-yl) - [1,4] diazepam-1-carboxylic acid tert-butyl ester 2.75 g (52% yellow oil isolated 1 H NMR (CDCl 3) d 8.19- 8.24 (m, 1 H), 8.06-8.12 (d, J = 9 Hz, 1 H), 7.54-7.68 (m, 2 H), 7.11 (m, 1 H), 3.47-3.74 (m, 8 H) , 1.98-2.16 (m, 2 H), 1.48 9 H); LCMS: 406,407,408. Coupling of aryl thiol catalyzed by palladium A 7-bromo-1-chloroisoquinoline (1 mmol) in butan-1-ol (20 mL) at room temperature was added sodium tert-butoxide (481 mg, 5 mmol), thiol (1.5 mmoles) and tetrakis triphenylphosphine palladium (60 mg, catalytic). The mixture was heated at 120 ° C for 16 hours. With warming to room temperature, the mixture was filtered through silica eluting with THF. Removal of the solvent under reduced pressure gave the crude product that was used without further purification in the subsequent step. INTERMEDIARY 12 4- [7- (2-Tert-Butyl-phenylsulfanyl) -isoquinolin-1-yl] -piperazine-1-carboxylic acid tert-butyl ester 4- (7-) 4- tert-butyl ester bromo-isoquinolin-1-yl) -piperazine-1-carboxylic acid (0.5 g, 1.3 mmol), 2-t-butyl-thiophenol (0.216 g, 1.3 mmol), Na-t-BuO (0.44 g, 4.5 mmol), Pd (PPh3) 4 (74 mg, 0.065 mmol) in n-BuOH (10 mL) was heated at 110 ° C, 3 h. The reaction mixture was filtered. The filtrate was concentrated and the residue was dissolved in ethyl acetate. The organic phase was washed with water (50 ml x 3), separated and dried (MgSO 4), filtered. The volatiles were evaporated and the residue was purified by flash column chromatography (S1O2, n-heptane: ethyl acetate 8: 2) to give 530 mg of the title compound as a colorless oil (86.4% yield). 1 H NMR (CDCl 3) d 8.05 (d, 1H), 7.65 (d, 1H), 7.20-7.45 (m, 5H), 7.15 (d, 1H), 3.26-3.40 (m, 4H), 3.10-3.20 (m , 4H), 2.5 (s, 3H), 1.38 (s, 9H). INTERMEDIARY 13 4- [7- (2-t-Butyl-phenylsulfane) -isoquinolin-1-yl] -piperazine-1-carboxylic acid tert-butyl ester A mixture of 4- (7-bromine) tert-butyl ester - isoquinolin-1-yl) -piperazine-1-carboxylic acid (0.5 g, 1.3 mmol), 2-t-butyl-thiophenol (0.216 g, 1.3 mmol), Nat-BuO (0.44 g, 4.5 mmol), Pd (PPh3 ) 4 (74 mg, 0.065 mmol) in n-BuOH (10 mL), was heated at 110 ° C, 3 hours. The reaction mixture was filtered. The filtrate was concentrated and the residue was dissolved in ethyl acetate. The organic phase was washed with water (50 ml x 3), separated and dried (MgSO 4), filtered. The volatiles were vaporized and the residue was purified by flash column chromatography (Si02, n-heptane: ethyl acetate 8: 2) to give 440 mg of the title compound as a colorless oil (yield 71%.) ¾ NMR (CDCl 3) d 8.00 - 8.10 (m, 2H), 7.15 -7.65 (m, 7H), 3.60-3.70 (m, 1H), 3.30-3.45 (m, 41-1), 3.05-3.20 (m, 3H) , 1.55 (s, 9H), 1.50 (s, 9H) INTERMEDIARY 14 4- [3,4-Dimethyl-phenylsulfanyl) -isoquinolin-1-yl] -piperazine-1-carboxylic acid tert-butyl ester 4- (7-bromo-isoquinolin-1-yl) -piperazine-1-carboxylic acid tert-butyl ester (0.5 g, 1.3 mmol), 3,4-dichlorothiophenol (165 μ ?, 1.3 mmol), NatBuO (0.44 g, 4.5 mmol), Pd (PPh3) (74 mg, 0.065 mmol) in n-BuOH (10 mL) was heated at 110 ° C, 3 hours. The reaction mixture was filtered. The filtrate was concentrated and the residue was dissolved in ethyl acetate. The organic phase was washed with water (50 ml x 3), separated and dried (MgSO.sub.1 < i), filtered. The volatiles were evaporated and the residue was purified by column chromatography (Si02, n-pentane: ethyl acetate 9.5: 0.5 -> 8: 2) to give 230 mg of the title compound as a colorless oil (36% yield) . XH EMR (CDCl 3) d 8.10-8.20 (m, 2H), 7.90 (bs, 1H), 7.65-7.75 (m, 2H), 7.10-7.55 (m, 3H), 3.50-3.65 (m, 4H), 3.20 -3.30 (m, 4H), 1.50 (s, 9H). INTERMEDIARY 15 4- [7- (3, 4-dimethyl-phenylsulfanyl) -isoquinolin-1-yl] piperazine-1-carboxylic acid tert-butyl ester 4- (7-bromobutyl) -butyl ester isoquinolin-1-yl) -piperazine-1-carboxylic acid (0.5 g, 1.3 mmol), 3,4-dimethyl-thiophenol (175 μ ?, 1.3 mmol), NatBuO (0.44 g, 4.5 mmol), Pd (PPh3) ( 74 mg, 0.065 mmol) in n-BuOH (10 mL) was heated at 110 ° C, 3 hours. The reaction mixture was filtered. The filtrate was concentrated and the residue was dissolved in ethyl acetate. The organic phase was washed with water (50 ml x 3), separated and dried (MgSOí), filtered. The volatiles were evaporated and the residue was purified by flash column chromatography (SiO2 n-pentane: ethyl acetate 9.5: 0.5 -> 8: 2) to give 260 rag of the title compound as a colorless oil (yield, 44% ). ¾ MR (CDCI3) d 8.00-8.10 (m, 2H), 7.55-7.65 (m, 3H), 7.40-7.50 (m, 1H), 7.10-7.30 (m, 2H), 3.30-3.40, (m, 4H) ), 3.10- 3.20, 4H), 2.30 (s, 3H), 2.25 (s, 3H), 1.50 (s, 9H). INTERMEDIARY 16 4- [7- (3,5-Dimethyl-phenylsulfanyl) -isoquinolin-1-yl] -piperazine-1-carboxylic acid tert-butyl ester 4- (7-bromine) -butyl ester isoquinolin-1-yl) -piperazine-1-carboxylic acid (0.5 g, 1.3 mmol), 3,5-dimethyl-thiophenol (180 mg, 1.3 mmol), NatBuO (0.44 g, 4.5 mmol), Pd (PPh3) 4 (74 mg, 0.065 mmol) in nBuOH (10 mL) was heated at 110 ° C, 3 hours. The reaction mixture was filtered. The filtrate was concentrated and the residue was dissolved in ethyl acetate. The organic phase was washed with water (50 ml x 3), separated and dried (MgSO 4) filtered. The volatiles were evaporated and the residue was purified by flash column chromatography (SiO2, n-pentane: ethyl acetate 9.8: 0.2 → 8: 2) to give 380 mg of the title compound as a colorless oil (yield, 65%) . ¾ fflffi (CDCI3) d 8.05-8.10 (m, 1H), 7.80-7.85 (m, 1H), 7.60-7.75 (m, 1H), 7.17-7.25 (m, 1H), 7.10 (bs, 2H), 7.00 (bs, 1H), 3.40-3.50 (m , 4H), 3.10-3.20 (m, 4H), 2.25 (bs, 6H), 1.50 (s, 9H). INTERMEDIARY 17 4- to7- (p-Chloro-phenylsulfanyl) -isoquinolin-1-β-piperazine-1-carboxylic acid tert-butyl ester A mixture of 4- (7-bromo-isoguinoline) -butyl ester - 1-yl) - piperazine-1-carboxylic acid (0.5 g, 1.3 mmol), p-chloro-thiophenol (188 mg, 1.3 mmol), NatBuO (0.44 g, 4.5 mmol), Pd (PPh3) 4 (74 mg, 0.065 mmole) in nBuOH (10 mL) was heated at 110 ° C, 3 hours. The reaction mixture was filtered. The filtrate was concentrated and the residue was dissolved - in ethyl acetate. The organic phase was washed with water (50 ml × 3), separated and dried (MgSOí), filtered. The volatiles were evpaorated and the residue was purified by flash column chromatography (SIO2, n-pentane: ethyl acetate 9.5: 0.5 - >; 8: 2) to give 300 mg of the title compound as a colorless oil (50% yield). ¾ NMR (CDC13) d 8.05-8.15 (m, 2H), 7.60-7.70 (m, 2H), 7.40-7.-50 (m, 2H), 7.15-7.30 (m, 3H), 3.45-3.55 (m , 4H), 3.10-3.15 (m, 4H), 1.50 (s, 9H). INTERMEDIARY 18 4- (7-Phenylsulfanyl-isoquinolin-1-yl) -piperazine-1-carboxylic acid tert-butyl ester LCMS: 422.423. INTERMEDIARY 19 4- a7- (4-tert-Butyl-phenylsulfanyl) -isoquinolin-1-yl] -piperazine-1-carboxylic acid tert-butyl ester LCMS: 478,479. INTERMEDIARY 20 4- (7- Phenylsulfanyl-isoquinolin-1-yl) - [1,4] diazepane-1-carboxylic acid tert-butyl ester: 368,369,370. INTERMEDIARY 21 4- [7- (4-tert-Butyl-phenylsulfanyl) -isoquinolin-1-yl] - [1,4] diazepane-1-carboxylic acid tert-butyl ester MS: 424.425.426. INTERMEDIARY 22 4- [7- (2-chloro-6-methyl-phenylsulfanyl) -isoquinolin-1-yl] - [1,4] diazepane-1-carboxylic acid tert-butyl ester MS: 416, 417, 418. INTERMEDIARY 23 4- [7- (3,4-Dimethylphenylsulfanyl) -isoquinolin-1-yl] - [1,4] diazepane-1-carboxylic acid tert-butyl ester MS: 396, 397, 398. INTERMEDIARY 24 Ester ter-butyl. 4- [7- (3,4-dichloro-phenylsulfanyl) -isoquinolin-1-yl] - [1,4] diazepane-1-carboxylic acid butyl ester MS: 436, 437, 438. INTERMEDIARY 25 Tert-butyl ester of 4-acid - [7- (4-chloro-phenylsulfanyl) -isoquinolin-1-yl] - [1,4] -diazepan-1-carboxylic acid MS: 402, 404. INTERMEDIARY 26 4- [7-. { 3,4-dimethyl-enylsulfanyl) -isoquinolin-1-yl] - [1,4] diazepane-1-carboxylic acid LCMS: 464, 465, 466. INTERMEDIARY 27 4- [7- (2- tert-butyl-phenylsulfanyl) -isoquinolin-1-yl] - [1/4] diazepane-1-carboxylic acid LCMS: 492, 493, 494. Deprotection of BOC and oxidation of thiols to sulfone derivatives Each thiol (0.2 - 1.14 mmol) it was dissolved in trifluoroacetic acid (1.5 ral) at 0 ° C and stirred for 15 minutes at this temperature. To this was added 33% solution of hydrogen peroxide (5-100 ml). The resulting mixture was stirred at room temperature for 90 minutes and then treated with sodium hydroxide solution (1M, 25 ml). Extraction of this mixture with ethyl acetate (3 x 50 mL) was followed by washing the combined organic layers with brine (50 mL). The organic extracts were removed under reduced pressure. The crude product was purified by preparative LCMS. Treatment of the purified material with HCl / Ether (1 M, 1 ml) gave the final product as a white solid. EXAMPLE 16 7- (2-Chloro-6-methyl-benzenesulfonyl) -1- piperazin-1-yl-isoquinoline hydrochloride A mixture of 4- [7- (2-chloro-6-methyl-) methylbutyl ester. phenylsulfanyl) -isoquinolin-1-yl] -piperazin-1-carboxylic acid (160 mg, 0.340 mmol), H202 (30% in water, 200 μ), trifluoroacetic acid (2 ml) was heated at 50 ° C, 2 hours . An aqueous solution of NaOH (1 N) (pH = 14) was added, ethyl acetate was added and the organic phase was separated, dried (MgSO 4), filtered. The filtrate was concentrated and the residue was purified by flash column chromatography (Si02, dichloromethane: methanol 8: 2) to yield 77 mg of the product compound as a free base (56% yield). The free base was converted to hydrochloride by treatment with HC1 in ethyl acetate. ½ MR (C¾OH-d4) d 8.88 (bs, 1H), 8.05-8.20 (m. 3H), 7. 65 (d, 1H), 7.35-7.55 (m, 3H), 3.85-3.95 (m, 4H), 3.00-3.15 (m, 4H), 2.95 (s, 3H). EXAMPLE 17 7- (2-t-Butyl-benzenesulfonyl) -1-piperazin-1-yl-isoquinoline hydrochloride A mixture of 4- [7- (2-t-butyl-phenylsulfani) -isoquinoline-1-tert-butyl ester. - il] - piperazine-1-carboxylic acid (273 mg, 0.571 mmol), ¾02 (30% in water, 1 mL), trifluoroacetic acid (3 mL) was heated at 50 ° C, 2 hours. The reaction was continued overnight at 35 ° C. An aqueous solution of NaOH (1 N) (pH = 14) was added, ethyl acetate was added and the organic phase was separated, dried (MgSO 4), filtered. The filtrate was concentrated and the residue was purified by flash column chromatography (Si02, dichloromethane: methanol 8: 2) to yield 50 mg of the title compound as the free base (yield, 56%.). in hydrochloride by treatment with diethyl ether HCl ¾ NMR (C¾OH-d4) d 8.55 (d, 1H), 8.25 (d, 1H), 7.95-8.10 (m, 3H), 7.55 (d, 1H), 7.55- 7.65 (m, 2H), 7.4 (d, 1?), 3.60-3.75 (m, 4H), 3.40-3.50 (m, 4H), 1.55 (s, 9H) EXAMPLE 18 Hydrochloride of 7- (3, 4) - dichlorobenzenesulfonyl) - 1-piperazin-1-yl isoquinoline A mixture of 4- [7- (3, 4- dichlorophenylsulfanyl) -isoguinolin-1-yl] -piperazine-1-carboxylic acid (230 mg, 0.47 mmol), ¾02 (30% in water, 0.5 ml), trichloroacetic acid (1.5 ml) was heated to 50 ° C. , 2 hours. The reaction was continued overnight at 35 ° C. An aqueous solution of NaOH (1 N) (pH = 14) was added, ethyl acetate was added and the aqueous phase was separated, dried (MgSO 4), filtered. The filtrate was concentrated and the residue was purified by flash column chromatography (SiO2, dichloromethane: methanol 9: 1). The free base was converted to hydrochloride by treatment with HCl in diethyl ether to obtain 45 mg of the title compound. ¾ NMR (CH3OH-d4) d 8.75-8.85 (m, 1H), 8.10-8.30 (m, 4H), 7.90-8.00 (m, 1H), 7.75-7.85 (m, 1H), 7.50-7.60 (m, -1H), 3.85-3.90 (m, 4H), 3.50-3.70 (m, 4H).

EXAMPLE 19 7- (3,4-Dimethyl-benzenesulfonyl) -1-piperazin-1-yl isoquinoline hydrochloride A mixture of 4- [7- (3,4-dimethylphenylsulphanyl) -isoquinoline- tert -butyl ester. 1- il] -piperazine-1-carboxylic acid (260 mg, 0.58 mmol), H2O2 (30% in water, 0.5 ml), trifluoroacetic acid (1.5 ml) was heated at 50 ° C, 2 hours. The reaction was continued overnight at 35 ° C. An aqueous solution of NaOH (1N) (pH = 14) was added, ethyl acetate was added and the organic phase was separated, dried (MgSO 4), filtered. The filtrate was concentrated and the residue was purified by flash column chromatography (SiO2, dichloromethane-methanol 9: 1). The free base was converted to hydrochloride by treatment with HCl in diethyl ether to obtain 20 mg of the title compound. 2H NMR (CH3OH-d4) d 8.75-8.80 (m, 1H), 8.10-8.25 (m, 3H), 7.70-7.85 (m, 2H), 7.60-7.70 (m, 1H), 7.35-7.40 (m, 1H), 3.90-4.00 (m, 4H), 3.55-3.65 (m, 4H), 2.35 (bs, 6H). EXAMPLE 20 7- (2,5-Dimethyl-benzenesulfonyl) -1-piperazin-1-yl-isoquinoline hydrochloride A mixture of 4- [7- (2,5-dimethyl-phenylsulfa-yl) - tert-butyl ester isoqunolin-1-yl] -piperazine-1-carboxylic acid (380 mg, 0.846 mmol), H2O2 (30% in water, 0.5 mL), trifluoroacetic acid (3 mL) was heated at 50 ° C, 2 hours. The reaction was continued overnight at 35 ° C. an aqueous solution of NaOH (1 N) (pH = 14) was added, ethyl acetate was added and the organic phase was separated, dried (MgSC, filtered, the filtrate was concentrated and the residue was purified by flash chromatography of column (Si02, dichloromethane: methanol 9.8: 0.2 -> 9.5: 0.5) The free base was converted to hydrochloride by treatment with HC1 in diethyl ether to obtain 120 mg of the title compound. ¾ MR (CH30H-d4) d 8.75 -8.80 (m, 1H), 8.25-8.30 (m, 1H), 8.05-8.20 (m, 2H), 7.60-7.70 (m, 3H), 7.3 0-7.3 5 (m, 1 H), 4.00-4 1 0 (m, 4H), 3.60-3.70 (m, 4H), 2.3 O-1.35 (bs, 6H) EXAMPLE 21 7- (p-Chlorobenzenesulfonyl) -1-piperazin-1-yl- hydrochloride isoquinoline A mixture of 4- al- (p-chlorophenylsulfane) -isoquinolin-1-yl] -piperazine-1-carboxylic acid tert-butyl ether (297 mg, 0.65 immoles), H202 (30% in water, 0.5 ml), trifluoroacetic acid (3 ml) was heated at 50 ° C, 2 h. The reaction was continued overnight at 35 ° C. An aqueous solution of NaOH (1 N) (pH = 14) was added, ethyl acetate was added and the organic phase was separated, dried (MgSC, filtered) The filtrate was concentrated and the residue was purified by flash chromatography column (Si02, dichloromethane: methanol 9.5: 0.5 → 9.0: 1.0) The free base was converted to hydrochloride by treatment with HC1 in diethyl ether to obtain 70 mg of the title compound ½ MR (CH3OH-d4) d 8.75-8.85 (ni, 2H), 8.10-3.25 (m, 3H), 8.00-8.08 (m, 2H), 7.60-7.68 (m, 3H), 3.85-3.95 (m, 4H), 3.55-3.65 (m, 4H) EXAMPLE 22 7-Benzenesulfoni-1- [1,4] diazepam-1-isoquinoline hydrochloride 30 mg ½ NMR (DMSO-de) d 9.3 (s, 1 H), 8.58 (s, 1 H), 8.26-8.30 (d, J = 9 Hz, 1 H), 8.1- 8.13 (m, 2 H), 8.01-8.06 (d, J = 6 Hz, 1 H), 7.6-7.76 (m, 3 H), 7.53-7.58 (d, J = 6 Hz, 1 H), 3.70-3.90 (m, 4H) 3.58-3.66 (m, 2 H), 3.29-3.40 (m, 2H); LCMS: 368.369 HPLC: 98%. EXAMPLE 23 7- (4-tert-Butyl-benzenesulfonyl) -1- [1,4] diazepan-1-yl) -isoquinoline hydrochloride 69 mg were isolated. ½ NMR (DMSO-d6) d 9.2 (s, 1 H), 8.65 (s, 1 H), 8.09-8.15 (d, J = 6 Hz, 1 H), 8.03-8.08 (d, J = 15 Hz, 1 H), 7.89-7.96 (d, J = 9 Hz, 2 H), 7.60-7.67 (d, J = 9 Hz, 2 H), 7.33-7.38 (d, J = 9 Hz, 1 H), 4.01 -4.09 (m, 2 H), 3.83-3.91 (m, 2 H), 3.43-3.52 (m, 2 H), 3.23-3.33 (m, 2 H), 1.25 (s, 9 H); LCMS: 424.425, HPLC: 97%. EXAMPLE 24 7- (2-Chloro-6-methyl-benzenesulfonyl) -1- [1,4] diazepan-1-yl) -isoquinoline hydrochloride 27 mg 1 H NMR (DMSO-d 6) d 8.81 (s, 1 H), 8.28 (m, 1 H), 8.10-8.18 (d, J = 6 Hz, 1 H), 7.94-8.08 (m, 2 H), 7.45-7.62 (m, 3 H), 7.36-7.42 ( d, J = 6 Hz, 1 H), 3.75-3.86 (m, 2H), 3.41-3.51 (m, 2 H), 3.18-3.32 (m, 2 H), 2.86 (s, 3 H), 2.14- 2.19 (m, 2 H); LCMS: 416, 418 HPLC: 98. EXAMPLE 25 7- (3,5-Dimethyl-benzenesulfonyl) -1- [1,4] diazepan-1-yl) -isoquinoline hydrochloride 62 mg ½ NMR (DMSO-de) d 9.35 (s, 1 H) were isolated , 8.67 (m, 1 H), 8.00-8.18 (m, 3 H), 7.58-7.69 (m, 2 H), 7.45-7.41 (d, J = 6 Hz, 1 H), 7.30-7.35 (m, 1 H), 4.06-4.14 (m, 2 H), 3.86-3.97 (m, 2 H), 3.42-3.52 (m, 2 H), 3.23-3.31 (m, 2 H), 2.33 (s, 6 M) 2.23-2.25 (m 2 H); LCMS: 436, 438, HPLC: 95% EXAMPLE 26 7- (3,4-Dichlorobenzenesulfonyl) - [1,4] diazepan-1-yl) isoquinoline hydrochloride isolated 11 mg. 1H NMR (CD3OD) d 8.88 (m, 1 H), 8.23-8.29 (d, J = 12Hz, 1 H), 8.13- 8.16 (d, J = 3 Hz, 1 H), 8.04-8.10 (d, J = 9 Hz, 1 H), 7.88-7.94 (d, J = 9 Hz, 1 H), 7.79- 7.84 (d, J = 6 Hz, 1 H), 7.67-7.73 (d, J = 9 Hz, 1 H), 7.42-7.46 (d, J = 6 Hz, 1 H), 4.28- 4.35 (ni, 2 H), 4.09-4.16 (m, 2?), 3.69-3.75 (m, 2 H), 2.33 -2.46 (m, 2 H); LCMS: 368, 369; HP1C: 97%. EXAMPLE 27 7- (4-Chlorobenzenesulfonyl) -1- [1,4] diazepan-1-yl) isoquinoline hydrochloride 41 mg ½ NMR (DMSO-de) d 9.27 (s, 1 H) were isolated, 8.68 (m, 1 H), 7.99-8.17 (m, 5 H), 7.66-7.75 (d, J = 9 Hz, 2 H), 7.33-7.39 (d, J = 6 Hz, 1 H), 4.03- 4.11 (m, 2 H), 3.83-3.93 (m, 2 H), 3.43-3.53 (m, 2 H), 3.23-3.32 (m, 2 H), 2.19-2.30 (m, 2 H); LCMS: 402, 404; HPLC: 98. EXAMPLE 28 7- (3,4-Dimethyl-benzenesulfonyl) -1- [1,4] diazepan-1-yl) -isoquinoline hydrochloride 10 mg ½ NMR (DMS0-d6) d 9.41 (s, 1 H) were isolated , 8.67 (s, 1 H), 8.00- 8.16 (m, 3 H), 7.76-7.82 (ra, 1 H), 7.68-7.77 (d, J = 9 Hz, 1 H), 7.32-7.42 (d, J = 9 Hz, 2 14), 3.99-4.40 (m, 4 H), 3.49 (m, 2 H), 3.33 (m, 2 H), 2.29 (s, 3 H), 2.25 (s, 3 H); LCMS: 396, 397; HPLC: 92%. EXAMPLE 29 7- (2-tert-Butyl-benzenesulfonyl) -1- [1,4] diazepan-1-yl) -isoquinoline hydrochloride 5 mg ¾ NMR (DMS0-d6) d 9.27 (s, 1 H) were isolated , 8.52 (s, 1 H), 8.06-8.16 (m, 2 H), 7.97-7.97 (m, 2 H), 7.72-7.78 (m, 1 H), 7.61-7.70 (m, 1 H), 7.40 -7.45 (d, J = 9 Hz, 2 H), 3.69-3.99 (m, 4 H), 3.43 (s, 2 H), 3.25 (s, 2 H), 2.05-2.26 (m, 2 H); 1.52 (s, 9 H); LCMS: 424, 425; HPLC: 90%. EXAMPLE 30 7- Benzenesulfonyl-1-piperazin-yl-isoquinoline Hydrochloride 10 mg 1 H NMR (DMSO-d 6) d 9.04 (s, 1 H), 8.65 (s, 1 H), 8.12-8.16 (d, J) were isolated. = 6 Hz, 1 H), 7.98-8.05 (m, 5 H), 7.58-7.72 (m, 2 H), 7.32-7.36 (d, J = 6 Hz, 1 H), 3.98-4.04 (in, 4 H), 3.80-3.86 (m, 4 H); LCMS: 354, 355; HPLC: 98%. EXAMPLE 31 7- (4-tert-Butyl-benzenesulfonyl-1-piperazin-1-yl-isoquinoline hydrochloride 10 mg 1 H NMR (DMSO-db) d 9.33 (s, 1 H), 8.57 (s, 1 H ), 8.24-8.29 (d, J = 9 Hz, 1 H), 8.11 (m, 2 H), 7.91-7.97 (d, J = 9 Hz, 2 H), 7.60-7.66 (d, J = 12 Hz , 2 H), 7.52-7.57 (d, J = 6 HZ, 1 H), 3.59-3.68 (m, 4 H), 3.29-3.40 (m, 4 H), 1.24 (s, 9 H); LCMS: 410, 411 HPLC: 90%.

Table 3 40 Chlorohydrate of 4-chloro- (4- ((3R) -p'molidm-3-yloxy) - 1-naphyric acid phosphide Reaction Scheme 4 Legends for Reaction Scheme 4: (i) tert-butyl 3-hydroxypyrrolidin-1-carboxylate or tert-butyl 4-hydroxypiperidin-1-carboxylate, PPh3, DEM), THF; (ii) ¾ (g), Pd / C, MeOH; (iii) P ^ -SC ^ Cl, pyridine, CH2C12; (iv) HC1 in diethyl ether General Method C The reaction of Mitsonobu of 4-nitro-1-naphthol with Boc-protected 3-hydroxypyrrolidine and 4-hydroxypiperidine 4-nitro-1-naphthol (1 equivalent) was dissolved in THF ( 3 ml / mmol), tert-butyl 3-hydroxypyrrolidin-1-carboxylate (2 equivalents) was added followed by PPh 3 (2 equivalent). The solution was preserved under N2 atmosphere and cooled with an ice bath. Ethyl azodicarboxylate (DEAD, 2 equivalents) was added dropwise. The ice bath was removed after 10 minutes and the reaction mixture was stirred at room temperature overnight. The solvent was evaporated and the residue re-dissolved in EtOAc. The formed precipitate was collected by filtration. The solution was concentrated in vacuo and purified by flash chromatography (SiO2, EtOAc: iso-hexane 2: 8 -> EtOAc). General Method D Reduction of Nitronaphthalene Derivatives To a solution of the corresponding nitrobaphthalenes (1 equivalent) (prepared by Generak Method A) in MeOH (2 ml / mmol), Pd / C (10%) and the reaction mixture were added. it was stirred overnight under nitrogen (1 atmosphere). The reaction mixture was filtered and the filtrate was concentrated in vacuo to give the corresponding aminonaphthalene derivatives. General Method E Reaction of Talented Aminone Derivatives with Sulfonyl Chlorides To a solution of the aminonaphthalene derivatives (1 equivalent) in CH2C12 (8 mL / branch1) was added pyridine (3 equivalent) followed by the corresponding sulfonyl chloride (1.2 equivalent) ). The mixtures were stirred at room temperature overnight, washed with HC1 (1M) (2 mL) and dried (MgSO4). The volatile materials were removed in vacuo and gave the crude product which was purified by flash chromatography (S1O2, EtOAc: iso-hexane 1: 4) to give the desired sulfonamide. General Method F Deprotection of the boc Group The sulfonamide derivatives (prepared by means of General Method C) were dissolved in a small amount of MeOH and treated with an excess of HC1 in diethyl ether (1M). Stirring at room temperature overnight resulted in a precipitate which was collected by filtration to give the title compounds as their hydrochloride salt. General Method G 3- Hydroxypyrrolidine (1 equivalent) was dissolved in MeOH (1 mL / bouquet1) and cooled on ice bath. (BOO2O (1.1 equivalents) was added and the mixture was stirred for 2 hours at room temperature, pyridine / water (10/10 ml) was added and the mixture was stirred overnight, evaporation of the solvents and co-evaporation. with toluene provided the desired bpc-protected 3-hydroxypyrrolidine INTERMEDIARY 28 3 - [(4-Nitro-1-naphthyl) oxy] pyrrolidin-1-carboxylic acid tert-butyl ester (General Method C) The crude product was purified by The compound was prepared from 4-nitro-1-naphthol (2.85 g, 15.1 mmol) The material thus obtained was dissolved in a small amount of EtOAc and iso-hexane was added, the solid formed was collected by filtration and triturated with MeOH to give the pure title compound 4.6 g (85%), 99% by HPLC, RT = 2.70 (Al system, 10-97% MeCN for 3 minutes), 1 H NMR (400 MHz, CDC13) d ppm 1.46 (d, J = 7.03 Hz, 9 H) 2.26-2.38 (m, 2 H) 3.60-3.81 (m, 4 R) 5.20 (br s, 1 H) 6.76 (d, J = 8.53 Hz, 1 H) 7.58 (t, J = 7.53 Hz, 1 H) 7.73 (t, J = 7.53 Hz, 1 H) 8.34 (dd, J = 20.33, 8.78 Hz, 2 H) 8.75 (d, J = 9.04 Hz, 1 H). MS (ESI +) for Ci9H22N205 m / z 376.2 (M + NH) +, 359.2 (M + H) +, 303.2 (M-tBu) + HPLC 99%, RT = 2.78 min (System Bl, 10-90% MeCN during 3 min). INTERMEDIARY 29 3- [(4-Amino-1-naphthyl) oxy] pyrrolidin-1-carboxylic acid tert-butyl ester (General Method D). The compound was prepared from intermediate 1 (2.6 g, 7.2 mmol), Yield: 2.1 g (87%) of the title compound as a purple solid. 96% by HPLC, RT = 1768 min (Al System, 10-97% MeCN for 3 minutes). 95% by HPLC, RT = 1,604 min (Bl System, 10-90% MeCN for 3 minutes). ¾ NMR (400 Mez, DMSO-d6) 8 PPM 1.37 (d, J = 22.59 Hz, 9 H) 2.12 (s, 2 H) 3.43-3.46 (m, 4 H) 4.96 (s, 1 H) 5.50 (s) , 2 H) 6.63 (d, J = 8.03 Hz, 1 H) 6.81 (d, J = 8.03 HZ, 1 H) 7.41 (dd, J = 6.02, 3.01 Hz, 2 H) 7.94-8.01 (m, 2 H). MS (ESI +) for Ci9H24N203 m / z 329.2 (M + H) +, 273.2 (M-tBu) +, 229.2 (M-Boc) +. INTERMEDIARY 30 3- [(4- {[[4-chlorophenyl) sulfonyl] amino} - 1-naphthyl) oxy] pyrrolidin-1-tert-butyl carboxylate (General Method E) The compound was prepared from the intermediary 2 (0.2 g, 0.61 mmol). The crude material was triturated with CH 3 CN to give 0.14 g (46%) of the title compound as a pale pink solid, 97% by HPLC, RT = 2,703 min (Al System, 10-97% MeCN for 3 minutes). ½ NMR (400 MHz, CDC13) d ppm 1.46 (d, J = 4.02 Hz, 9 H) 2.18-2.30 (m, 2 H) 3.54-3.76 (m, 4 H) 5.05 (br s, 1 H) 6.62- 6.65 (m, 1 H) 6.74-6.76 (m, 1 H) 7.17-7.23 (m, 1 H) 7.32 (d, J = 9.04 Hz, 2 H) 7.39-7.45 (m, 2 H) 7.62 (d, J = 8.53 HZ, 2 H) 7.68-7.72 (m, 1 H) 8.16-8.19 (m, 1 H) M (ESI +) for C25H27CIN2O5S m / z 520.2 (M + NH4) +, 447.0 (M-tBu) +.

HPLC 98%, RT = 2738 min (Bl System, 10-90% MeCN for 3 min). INTERMEDIARY 31 3- [(4- { [ { 4-methoxyphenyl) sulfonyl] amino} - 1-naphthyl) oxy] pyrrolidin-1-tert-butyl carboxylate The compound was prepared from intermediate 2 (0.2 g, 0.61 mmol), Product: 0.2 g (66%) of the title compound as a pink oil. 98% by HPLC, RT = 2617 min (Al System, 10-97% MeCN for 3 minutes). ¾ NMR (400 MHz, CDC13) d ppm 1.45 (d, J = 5.02 Hz, 9 H) 2.14-2.31 (m, 1 H) 3.54-3.76 (m, 4 H) 3.79 (s, 3H) 5.04 (br s, 1 H) 6.60-6.65 (m, 2 H) 6.81 (d, J = 8.53 12 H) 7.15-7.24 (m, 1 H) 7.3 8-7.44 (m, 2 H) 7.60-7.64 (m, 2 H) 7.71-7.76 (m, 1 H) 8.14- 8.18 (m, 1 H). MS (ESI +) for C26H30N2O6S m / z 516.4 (M + N¾) +, 443.0 (M-tBu) +, 399.2 (M-Boc) +. INTERMEDIARY 32 3- [(4- {[[5- chloro-2-thienyl) sulfonyl] amino} - 1-naph il) oxy] pyrrolidin-1-tert-butyl carboxylate (General Method E) prepared the compound from intermediate 2 (0.2 g, 0.61 mmol), Product: 0.21 g (68%) of the title compound as a yellow solid. 99% by HPLC, RT = 2777 min (Bl System, 10-90% MeCN for 3 minutes). 1 H NMR (400 μMz, CDC13) d ppm 1.46 (d, J = 6.02 Hz, 9 H) 2.16-2 (m, 2 H) 3.55-3.74 (m, 4 H) 5.07 (br s, 1 H) 6.67- 6.70 (m, 1 H) 6.75 (d, J = 4.02 Hz, 1 H) 6.77 (br s, 1 H) 7.13 (br s, 1 H) 7.28-7.35 (m, 1 H) 7.46-7.48 (m, 2 H) 7.75-7.79 (m, 1 H) 8.19-8.22 (m, 1 H). MS (ESI +) for C23H25CIN2O5S2 m / z 526.2 (M + NH4) +, 453.0 (M-tBu) +, 409.2 (M-Boc). HPLC 99%, RT = 2767 min (Al System, 10-97% MeCN for 3 min). INTERMEDIARY 33 4- [(4-nitro-1-naph il) oxy] -1-tert-butyl carboxylate (General Method C) The compound was prepared from 4-nitro-1-naphthol (2 g, 10.6 mmol). The material obtained after instantaneous cormatography was not pure in accordance with NMR. Recrystallization from EtOAc / iso-hexane gave 2.3 g (62%) of the title compound as a yellow solid. 98% by HPLC, RT = 2842 (Al System, 10-97% MeCN for 3 minutes. ½ NMR (400 MHz, CDC13) d ppm 1.48 (s, 9 H) 1.99 (m, 4 H) 3.54 (m, 2 H) 3.70 (m, 2 H) 4.87 (m, 1 H) 6.82 (d, J = 9.04 Hz, 1 H) 7.59 (m, 1 H) 7.74 (m, 1 H) 8.38 (d, J = 8.53 Hz, 2 H) 8.77 (d, J = 8.53 Hz, 1 H) MS (ESI +) for C2oH24 205 m / z 373.0 (M + H) +, 390.2 (M + NH4), 317.0 (M-tBu) + HPLC 98%, RT = 2973 min (Bl System, 10-90% MeCN for 3 min).

INTERMEDIARY 34 4- [(4-Amino-1-naphthyl) oxy] piperidin-1-tert-butyl-carhoxylate (General Method C) The compound was prepared from intermediate 6 (2.3 g, 7.0 mmol), Product: 2 g (95%) as yellow oil. 94% by HPLC, RT = 2885 min (Bl System, 10-90% MeCN for 3 minutes). XH NMR (400 MHz, CDC13) d ppm 1.46 (s, 9 H) 1.80-1.98 (m, 4 H) 3.35-3.41 (m, 2 H) 3.46 (s, 3 H) 3.69-3.75 (m, 2 H ) 3.88 (br s, 1 H) 4.50-4.54 (m, 1 H) 7.45-7.50 (m, 2 H) 7.79-7.81 (m, 1 H) 8.22-8.24 (m, 1 H). MS (ESI +) for C20H26 2O3 m / z 343.2 (M + H) +. HPLC 94%, RT = 2735 min (Al System, 10-97% MeCN for 3 min). INTERMEDIARY 35 4- [(4- {[[4-chlorophenyl) sulfonyl] amino} - 1-naphthyl) oxy] piperidin-1-tert-butyl carboxylate (General Method E) The compound was prepared from the intermediate 7 (0.25 g, 0.73 mmole), Product: 0.29 g (77%). 98% by HPLC, RT = 2,906 min (Al System, 10-97% MeCN for 3 minutes). XH NMR (400 MHz, CDCl 3) d ppm 1.47 (s, 9 H) 1.88 (m, 2 H) 1.98 (m, 2 H) 3.47 (m, 2 H) 3.68 (m, 2 R) 4.69 (m, 1 H) 6.61 (s, 1 H) 6.70 (d, J @ 8.03 Hz, 1 H) 7.17 (d, J = 8.03 HZ, 1 H) 7.32 (m, 2 H) 7.43 (m, 2 H) 7.62 (m , 2 H) 7.70 (m, 1 H). MS (ESI +) for C26H29CIN2O5S m / z 534.0 (M + NH4) +, 461.2 (M-tBu) +. HPLC 98%, RT = 2843 min (Bl system, 10-90% MeCN for 3 min). INTERMEDIARY 36 4- [(4- {[[4- (Methoxy) sulfonyl] amino} - (1-naphthyl) oxy] piperidin-1-tert-butyl carboxylate (General Method E) The compound was prepared from the Intermediary 7 (0.25 g, 0.73 mmol). Product: 0.21 g (56%) of the title compound as a pink solid. 100% by HPLC, RT = 2755 min (Al System, 10-97% MeCN for 3 minutes). ¾ NMR (400 MHz, CDC13) d ppm 1.47 (s, 9 H) 1.86-2.01 (m, 4 H) 3.43-3.49 (m, 2 H) 3.65-3.71 (m, 2 H) 3.79 (s, 3 H) 4.65-4.70 ( m, 1 H) 6.58 (s, 1 H) 6.69 (d, J = 8.53 Hz, 1 H) 6.83-6.79 (m, 2 H) 7.17 (d, J = 8.03 Hz, 1 H) 7.39-7.44 (m , 2 H) 7.61-7.64 (m, 2 H) 7.75-7.77 (m, 1 H) 8.21-8.24 (m, 1 H). MS (ESI +) for C27H32N2O6S m / z 530.2 (M + NH4) +, 457.2 (M-tBu) +, 413.4 (M-Boc) +. HPLC 99%, RT = 2668 min (Bl System, 10-90% MeCN for 3 min). INTERMEDIARY 37 4- [(4- {[[5- fXuoro-2-methylphenyl) sulfonyl] amino} -1- naphthyl) oxy] piperidin-1-tert-butyl carboxylate (General Method E) The compound was prepared from 4- [(4-amino-naphthyl) oxy] piperidin-1-tert-butyl carboxylate (0.25 g, 0.73 mmol). Product: 0.24 g (64%) of the title compound as a pink solid. 99% by HPLC, ¾ = 2,809 min (Bl System, 10-90% MeCN for 3 minutes). ¾ NMR (400 MHz, CDC13) d ppm 1.46 (s, 9 H) 1.83-1.98 (i, 4 H) 2.54 (s, 3 H) 3.42-3.48 (M, 2 H) 3.63-3.69 (m, 2 H) 4.64-4.68 (m, 1 H) 6.64-6.68 (m, 2 H) 7.03 (d, J = 8. 53 Hz, 1 H) 7. 1 0 (m, 1 H) 7.22 (dd, J = 8.53, 5.02 Hz, 1 H) 7.44-7.48 (m, 2 H) 7.55 (dd, J == 8.53, 2.51 Hz, 1 H) 7.83-7.86 (m, 1 H) 8.24 (m, 1 H). MS (ESI +) for C27H31FN2O5S m / z 532.2 (M + M) +, 459.2 (M-tBu) +, 415.2 (M-Boc) +. HPLC 100%, RT = 2877 min (Al System, 10-97%, MeCN for 3 min). INTERMEDIARY 38 4- [(4- {[[5- chloro-2-thienyl) sulfonyl] aminoa} - 1-naphthyl) oxy] piperidin-1-tert-butyl carboxylate (General Method E) Prepared the compound from 4- [(4-amino-1-naphthyl) oxy] piperidin-1-tert-butyl carboxylate (0.25 g, 0.73 mol). Product: 0.25 g (65%) of the title compound as a pink solid. 98% by HPLC, RT = 2827 (Bl System, 10-90% MeCN for 3 minutes). aH NMR (400 MHz, CDCl 3) d ppm 1.47 (s, 9 H) 1.86-2.03 (m, 4 H) 3.45-3.51 (m, 2 T 3.66-3.72 (m, 2 H) 4.69-4.74 (m, 1 H) 6.66 (s, 1 H) 6.74-6.76 (m, 2 H) 7.14 (d, J = 4.02 Hz, 1 H) 7.30 (d, J = 8.03 Hz, 1 H) 7.45-7.50 (m, 2 H) 7.76-7.79 (m, 1 H) 8.25-8.28 (m, 1 H) MS (ESI +) for C24H27C1 205S2 m / z 540.4 (M + N¾) +, 467.2 (M-tBu) +. HPLC, 99%, R = 2910 min (Al System, 10-97% MeCN for 3 min.) INTERMEDIARY 39 (3R) -3-hydroxypyrrolidin-1-tert-butyl carboxylate (General Method G) Compound was prepared from (3R) -3 -hydroxypyrrolidine (5 g, 57.4 mmol) Product 9.6 g (90%) of the title compound ½ NMR (400 MHz, CDC13) d ppm 1.43 (s, 9 H) 1.90-1.98 (m 2 H) 3.27-3.47 (m, 4H) 4.40 (br s, 1H) INTERMEDIARY 40 (3S) -3-hydroxypyrrolidin-1-tert-butyl carboxylate (General Method G) The compound was prepared from (3S) -3-hydroxypyrrolidine (5 g) 57.4 mmoles) Product: 8 g (86%) of the title compound ½ NMR (400 MHz, CDC13 d ppm 1.40 (s, 9H) 1.86- 1.91 (m, 2H) 3.24-3.42 (m, 4H) 4.36 (br s, 1H). INTERMEDIARY 41 (3S) -3- [(4-Nitro-1-naphthyl) oxy] pyrrolidin-1-carboxylic acid tert-butyl ester (General Method C) The compound was prepared from (3R) -3-hydroxypyrrolidin-1-carboxylate of tert-butyl (3.56 g, 19 mmol) and 4-nitro-1-naphthol (3 g, 15.9 mmol). Product: 5 g (88%) of the title compound as yellow oil. ?? NMR (400 MHz, CDC13) d ppm 1.45 (d, J = 7.03 Hz, 9 H) 2. 22-2.38 (m, 2 H) 3.54-3.83 (m, 4 H) 5.18 (br s, 1 H) 6.74 (d, J = 8.53 Hz, 1 H) 7.56 (t, J = 7.78 Hz, 1 H) 7.71 (t, J = 7.78 Hz, 1 H) 8.29 (d, J = 8.53 Hz, 1 H) 8.33 (d, J = 8.53 Hz, 1 H) 8.72 (d, J = 8.53 Hz, 1 H). MS (ESI +) for C19H22Ñ2O5 m / z 376.2 (M + N¾) + 303.2 (M- tBu). HPLC 100%, RT = 2768 min. (Al system, 10-97% MeCN for 3 min). INTERMEDIARY 42 (3R) -3- [(4-Nitro-1-naphthyl) oxy] pyrrolidin-1-carboxylic acid tert-butyl ester (General Method C) The compound was prepared from (3S) -3-hydroxypyrrolidin-1-carboxylate of tert-butyl (3.56 g, 19 mmol) and 4-nitro-1-naphthol (3 g, 15.9 mmol). Product: 2.8 g (49%) of the title compound as yellow oil ¾ NMR (400 MHz, CDC13) d ppm 1.46 (d, J = 7.03 Hz, 9H) 2. 26-2.38 (m, 2 H) 3.55-3.81 (m, 4 H) 5.20 (br s, 1 H) 6.77 (d, J = 8.53 Hz, 1 H) 7.59 (t, J = 7.53 Hz, 1 H) 7.72-7.76 (m, 1 H) 8.32 (d, J = 8.03 Hz, 1 H) 8.37 (d, J = 8.53 Hz, 1 H) 8.76 (d, J = 8.53 Hz, 1 H). HPLC 95%, RT = 2775 min (System Al, 10-97% MeCN for 3 min).

INTERMEDIARY 43 (3S) - 3- [. { 4- Amino-1-naphthyl) oxy] pyrrolidin-1-carboxylic acid tert-butyl ester (General Method D) The compound was prepared from (3S) ~ 3- [(4-nitro-1-naphthyl) oxy] pyrrolidin-1 - tert-butyl carboxylate (5 g, 14 immoles). Product: 3.5 g (76) of the title compound as a dark pink solid. ¾ NMR (400 MHz, CDC13) d ppm 1.46 (d, J = 14.56 Hz, 9 H) 2.08-2.13 (m, 1 H) 2.27-2.30 (m, J = 13.05 Hz, 1 H) 3.54-3.77 (m , 4 H) 3.88 (br s, 2 H) 4.96 (br s, 1 H) 6.65-6.70 (m, 2 H) 7.45-7.51 (m, 2 H) 7.79-7.81 (m, 1 H) 8.15-8.19 (m, 1H). MS (ESI +) for CisH24 203 m / z 329.2 (M + H) +, 273.2 (M-tBu) 4, 229.2 (M-Boc) +. HPLC 95%, RT = 1854 min (Al System, 10-97% MeCN for 3 min). INTERMEDIARY 44 (3R) -3- [(4-amino-1-naphthyl) oxy] pyrrolidine-1-carboxylate (General Method D) The compound was prepared from (3R) -3 - [(4-nitro-1-naphthyl ) oxy-pyrrolidin-1-tert-butyl carboxylate (2.8 g, 7.8 mmol). Product: 1.8 g (72%) of the title compound as a dark pink solid. ¾ NMR (400 MHz, CDCI3) 5 ppm 1.46 (d, J = 14.56 Hz, 9 H) 2.07-2.14 (m, 1 H) 2.27-2.30 (m, 1 H) 3.54-3.77 (m, 4 H) 3.93 (br s, 2 H) 4.96 (br s, 1 H) 6.65-6.70 (m, 2 H) 7.45-7.51 (m, 2 H) 7.79-7.81 (m, 1 H) 8.16-8.18 (m, IH) .

MS (ESI +) for Ci9H24N203 m / z 329.2 (M + H) +, 273.2 (M-tBu) +, 229.2 (M-Boc) +. HPLC 94%, RT = 1751 min (System Al, 10-97% MeCN for 3 min). INTERMEDIARY 45 (3S) - 3- [(4- {[[4-chlorophenyl) sulfonyl] amino} - 1 -naphthyl) oxy] pyrrolidin-1-tert-butyl carboxylate (General Method E) Prepared the compound from (3S) -3- [(4-nitro-1-naphthyl) oxy] pyrrolidin-1-carboxylate (0.3 g, 0.9 mmol) and 4-chloro-phenylsulphonyl-4-chlorochloride (0.23 g, 1.1 mmoles). Product: 0.23 g (50%) of the title compound. ¾ NMR (400 MHz, CDC13) d ppm 1.46 (d, J = 4.52 Hz, 9 H) 2.15-2-34 (m, 2 H) 3.54-3.74 (m, 4 H) 5.05 (br s, 1 H) 6.62-6.71 (m, 2 H) 7.17-7.23 (m, 1 H) 7.33 (d, J = 8.53 Hz, 1 H) 7.39-7.43 (m, 2 H) 7.62-7.64 (M, 2 H) 7.65- 7.70 (rn, J = 6.02 Hz, 1 H) 8.18 (d, J = 8.53 Hz, 1 H) MS (ESI +) for C25H27CIN2O5S m / z 520.2 (M + H4) +, 447.0 (M-tBu) +. 100% HPLC, RT = 2772 min (Al System, 10-97% MeCN for 3 min). INTERMEDIARY 46 (3R) -3- [(4- {[[4-chlorophenyl) sulfonyl] amino} - 1 -naphthyl) oxy] pyrrolidin-1-tert-butyl carboxylate (General Method E) Prepared the compound from (3R) -3- [(4-nitro-1-naphthyl) oxy] pyrrolidin-1-tert-butyl carboxylate (0.3 g, 0.9 mmol) and 4-chloro-phenylsulfonyl chloride (0.23 g, 1.1 mmoles). Product: 0.4 g (87%) of the title compound. XH MR (400 MHz, CDC13) d ppm 1.46 (d, J = 4.52 Hz, 9 H) 2.15-2-34 (m, 2 H) 3.54-3.74 (m, 4 H) 5.05 (br s, 1 H) 6.60-6.66 (m, 2 H) 7.17-7.23 (m, 1 H) 7.33 (d, J = 8.53 Hz, 1 H) 7.39-7.43 (m, 2 H) 7.62-7.64 (m, 2 H) 7.65- 7.70 (m, 1 = 6.02 Hz, 1 H) .S. 1 8 (d, J = 8.53 Hz, 1 H) MS (ESI +) for C25H27CIN2O5S? A /? 520.2 (M + NH4) +, 447.0 (M-tBu) +. 100% HPLC, RT = 2769 m / z (Al System, 10-97% MeCN for 3 min). EXAMPLE 32 4- Chloro-N- [4- (pyrrolidin-3-yloxy) -1-na tyl] benzenesulfonamide hydrochloride (General Method F) The compound was prepared from intermediate 3 (0.13 g, 0.26 mmol). The solid was further purified by trituration with diethyl ether to give 0.11 g (95%) of the title compound as a white solid. 99% by HPLC, RT = 1810 min (Al System, 10-97% MeCN for 8 minutes). lE (400 MHz, DMSO-ds) d ppm 2.21-2.26 (m, 2 H) 3.32-3.37 (m, 2 H) 3.48-3.50 (m, 2 H) 5.28 (br s, 1 H) 6.91-6.98 ( m, 2 H) 7.44-7.50 (m, 2 H) 7.56-7.64 (m, 4 H) 7.88-7.90 (m, 1 H) 8.20-8.23 (m, 1 H). MS (ESI +) for C2oHi9ClN203S m / z 401.2 (M + H) +. HPLC 98%, RT = 1651 min (Bl system, 10-90% MeCN for 3 min).

EXAMPLE 33 4- Methoxy-N- [4- (pyrrolidin-3-yloxy) -1-naphthyl] benzenesulfonamide hydrochloride (General method F) The compound was prepared from intermediate 4 (0.18 g, 0.36 mmol), Product: 0.12 g (76%) of the title compound as a white solid. 100% by HPLC, RT = 1490 min (System Bl, 10-90% MeCN for 3 minutes.) NMR (400 MHz, DMS0-d6) 3 ppm 2.20-2.25 (m, 2 H) 3.31- 3.53 (m, 4 H) 3.78 (s, 3 H) 5.27 (br s, 1 H) 6.90-6.97 (m, 2 H) 7.00 (d, J = 8.53 Hz, 2 H) 7.43-7.48 (m, 2 H) 7.57 (d, J = 8.53 Hz, 2 H) 7.93-7.96 (, 1 H) 8.19-8.22 (m, 1 H) 9.63 (br s, 2 H), MS (ESI +) for C2iH22N204S m / z 409.2 (M + H) +. HPLC 100%, RT = 1639 min (Al System, 10-97% MeCN for 3 min.) EXAMPLE 34 5- Chloro- N- [4- (pyrrolidin-3-yloxy) -1- hydrochloride Naphthyl] thiophene-2-sulfonamide (General Method F) The compound was prepared from intermediate 5 (0.20 g, 0.39 mmol), Product: 0.14 g (80%) of the title compound as a pale white solid. 99% by HPLC, RT = 1651 min (Bl System, 10-90% MeCN for 3 minutes).

¾ NMR (400 MHz, DMSO-d6) 5 ppm 2.23-2.26 (m, 2 H) 3.28- 3.39 (m, 2 H) 3.40-3.56 (m, 2 H) 5.32 (br s, 1 H) 6.99 (d , J = 8.53 Hz, 1 H) 7.13 (d, J = S. (3 Hz, 1 H) 7.15 (d, J = 4.02 Hz, 1 H) 7.26 (d, J = 4.02 Hz, 1 H) 7.48- 7.52 (m, 2 H) 7.92 (dd, J = 6.53, 3.01 Hz, 1 H) 8.25 (dd, J = 6.53, 3.01 Hz, 1 H) 9.60 (s, 1 H) MS (ESI +) for CisHrCl zOsSz m / z 409.2 (M + H) +. HPLC 99%, RT = 1818 min (Al System, 10-97% MeCN for 3 min.) EXAMPLE 35 4- Chloro-N- [4- (piperidine-3 - iloxy) - 1-naphthyl] benzenesulfonamide (General Method F) The compound was prepared from intermediate 8 (0.26 g, 0.50 mmole), Product: 0.12 g (53%) of the title compound as a white solid. 100% HPLC, RT = 1872 minutes (Al System, 10-97% MeCN for 3 minutes). XH NMR (400 MHz, DMSO-d6) d ppm 1.95-1.99 (m, 2 H) 2.14-2.19 (m, 2 H) 3.11 (br s, 2 H) 3.26 (br s, 2 H) 4.84 (br s , 1 H) 6.92-6.99 (m, 2 H) 7.44-7.51 (m, 2 H) 7.57-7.65 (m, 4 H) 7.91 (d, J = 7.53 Hz, 1 H) 8.17 (d, J = 7.03 Hz, 1 H) 8.94 (br s, 1 H) 9.05 (br s, 1 H) 10.11 (s, 1 H). MS (ESI +) for C2iH2iClN203S m / z 415.2 (M + H) HPLC 99%, RT = 1657 min (System Bl, 10-90% MeCN for 3 min). EXAMPLE 36 4- Mexy-N- [4- (piperidin-3-yloxy) -1-naphthyl] benzenesulfonamide hydrochloride (General Method F) The compound was prepared from Intermediary 9 (0.19 g, 0.37 min.), Product: 0.15 g (90%) of the title compound as a white solid. 97% by HPLC, RT = 1,508 min (Bl System, 10-90% MeCN for 3 minutes). XE NMR (400 MHz, DMS0-d6) d ppm 1.96 (m, 2 H) 2.16 (m, 2 H) 3.10 (m, 2 H) 3.26 (m, J = 6.02 Hz, 2 H) 3.78 (s, 3 H) 4.82 (m, 1 H) 6.95 (q, J = 8.20 Hz, 1 H) 7.01 (d, J = 9.04 Hz, 2 H) 7.47 (m, 2 H] 7.57 (m, 2 H) 7.96 (m , 1 H) 8.16 (m, 1 H) 8.96 (s, 1 H) 9.07 (s, 1 H) 9.81 (s, 1 H) MS (ESI +) for C22H2 N204S m / z 413.4 (M + H ) +. HPLC 97%, RT = 1713 min (Al System, 10-97% MeCN for 3 min.) EXAMPLE 37 5- Fluoro-2-methyl-N- [4- (piperidin-4-yloxy) -hydrochloride 1- naphthyl] benzenesulfonamide (General Method F) The compound was prepared from intermediate 10 (0.24 g, 0.47 mmol). Product: 0.21 g (99%) of the title compound as a whitish solid. 100% by HPLC, RT = 1823 minutes (Al System, 10-97% MeCN for 3 minutes) ½ NMR (400 MHz, C¾OH-d4) d ppm 2.13 (m, 4 H) 2.42 (s, 3 H) 3.18 (m, 2 H) 3.37 (, 2 H) 4.83 (m, 1 H) 6.81 (d, J = 8.53 Hz, 1 H) 6.97 (d, J = 8.03 Hz, 1 H) 7.10 (m, 1 H) 7.24 (m, J = 8.53, 5.52 Hz, 1 H) 7.35 (m, 3 H) 7.83 (m, 1 H) MS (ESI +) for C22H23FN2O3S m / z 415.2 (M + H) + HPLC 96%, RT = 1628 min (System B 1, 10-90% MeCN for 3 min.) EXAMPLE 38 5- Chloro-N- [4- (piperidin-4-yloxy) -1-naphthyl] thiophene-2-sulfonamide hydrochloride ( General Method F) The compound was prepared from 4- [(4- {[[5- (5-fluoro-2-methylphenyl) -sulfonyl] amino]} - (1-naphthyl) oxy] piperidine-1-carboxylate of ter- Butyl (0.24 g, 0.46 mmol) Product: 0.16 g (76%) of the title compound as a white solid.1H NMR (400 MHz, DMSO-d6) d ppm 1.96-2.03 (m, 2 H) 2.16-2.22 (m, 2 H) 3.09-3.14 (m, 2 H) 3.25-3.31 (m, 2 H) 4.86-4, 89 (m, 1 H) 7.04-7.11 (m, 2 H) 7.16 (d , J = 4.02 Hz, 1 H) 7.26 (d, J = 4.02 Hz, 1 H) 7.48-7.53 (m, 2 H), 7.92-7.94 (m, 1 H) 8.19-8.21 (m, 1 H) 9.06 (br s, 1 H) 10.3 6 (br s, 1 H) . MS (ESI +) for CigHigClNaOsSz m / z 423.0 (M + H) +. HPLC 99%, RT = 1861 min (Al System, 10-97% MeCN for 3 min). EXAMPLE 39 4- Chloro-N- Hydrochloride. { 4- [(3S) -pyrrolidin-3-yloxy] -1-naphthyl} benzenesulonamide (General Method F) The compound was prepared from (3S) -3- [(4- {[[4-chlorophenyl) sulfonyl] amino]} - 1-naphthyl) pyrrolidin-1-carboxylate of tert-butyl (0.22 g, 0.44 mmol). Product: 0.15 g (78%) of the title compound as a yellow solid. 2 H NMR (400 MHz, CH 3 OH-d 4) d ppm 2.37-2.49 (m, 2 H) 3.52-3.56 (m, 2 H) 3.61-3.71 (m, 2 H) 5.37 (br s, 1 H) 6. 87 (d, J = 8.03 Hz, 1 H) 7.14 (d, J = 8.03 Hz, 1 H) 7.38-7.47 (m, 4 H) 7.61 (d, J = 8.53 Hz, 2 H) 7.83 (d, J = 8.03 Hz, 1 H) 8.22 (d, J = 8.03 Hz, 1 H). MS (ESI +) for C20H19CIN2O3S m / z 403.2 (M + H) +. 100% HPLC, RT = 1826 min (Al System, 10-97% MeCN for 3 min). EXAMPLE 40 Chlorohydrate of 4-chloro- N-. { 4- [(3R) ~ pyrrolidin-3-yloxy] -1-mafethyl} Benzenesulfonamide (General Method F) The compound was prepared from (3R) -3- [(4- {[[(4-chlorophenyl) sulfonyl] amino} - 1. naphthyl) oxy] pyrrolidin-1-carboxylate of ter - Butyl (0.37 g, 0.74 mmol). Product: 0.27 g (83%) of the title compound as a blacuzco solid. XH NMR (400 MHz, CH 3 OH-C 4) d ppm 2.37-2.49 (m, 2 H) 3.52-3.56 (m, 2 H) 3.61-3.71 (m, 2 H) 5.37 (br s, 1 H) 6. 88 (d, J = 8.53 Hz, 1 H) 7.15 (d, J = 8.03 Hz, 1 H) 7.39-7.47 (m, 4 H) 7.60-7.62 (m, 2 H) 7.83 (d, J = 7.53 Hz, 1 H) 8.22 (d, J = 8.03 Hz, 1 H). MS (ESI +) for C20H19CIN2O3S m / z 403.2 (M + H +). 100% HPLC, RT = 1815 min (Al System, 10-97% MeCN for 3 min).

Table 4 4- (4-methylpiperazin-1-yl) -N- (1- (1-naffjl) etui) thien (3,2-c) pyridyryl-2-ylifonamide hydrochloride 4- (4-methyl-piperazin-1-yl) -N- (4-hexylphenyl) -1iena (3,2-c) pyridin-2-sulfonamide 6 1 hydrochloride N- (3-chlorobenzyl) -4- (4-methylpiperazin-1-yl) thieno (3,2-e) pyridin-2-suifonamide ¾ 1xr H 4- (4-methylpiperazin-1H-yl) - N- (1- (4-fluorophenyl) etl) -sily (3,2-c) pyridin-2-ylifonamide hydrochloride N- (2,3-dffluorobenzyl) -4- o -hydrochloride. , ° H (4- metrlpiperane-1-yl) thieno (3.2-c) pyridin-2-suifonamide 4- (4-methyl-piperazin-1-yl) -N- (4-chloro-2, 5-dimethoxy-phenyl) l-ene (3,2-c) pyridin-2-sulfonamide Y-hydrochloride 2-bromo- (4-Br-methyl-piperazin-1-yl) -MI- (2-cyclohex-1-en-1-ylethyl) -tjeno (3,2-c) pyridin-3-sulfonamide 6-Y hydrochloride 2- (2-bromo-4- (4-methy1-piperazin-Br-4-l) l) -benzo (b) thiophene-3-sulfonyl-1, 2,3,4-tetrahydro-isoquinoline ¾efoo 9 2- bromo-4- (4- Br .. i merj'lpiperazin-1-yl) -N- (1- (4-fluorophenyl) etiitiene (3,2-o) pyridin-3-suifonamide F-hydrochloride 2- bromo-4- (4- Br metJpíperazin-1-yl) - - (4-doro) - (2,5-d-methoxyphenyl) -1-ene (3,2-c) pyrfc // n-3- hydrochloride suffonamida F Reaction Scheme 5 Legends of Reaction Scheme 5: i) Malonic acid, pyridine, piperidine, heat; ii) ethyl chloroformate, acetone, NaN 3 - 10 ° C; iii) diphenyl ether, 220 ° C; iv) POCl3, heat; v) S02 gas, n-BuLi, N-chlorosuccinimide, CH2C12; vi) R1 ^, pyridine; vii) HR3, K2C03, DMSO, heat. INTERMEDIARY 47 Acid (2E) -3- (5-bromothien-2-yl) acrylic Malonic acid (44.40 g, 426.7 mmol) was added to a mixture of 5-bromothiophen-2-carbaldehyde (50 g, 261.7 mmol.). , piperidine (2.84 ml) and pyridine (150 ml) The mixture was refluxed for 1 hour at 80 ° C and then at 100 ° C overnight The volatile materials were evaporated and the residue dissolved in water and acidified with Hydrochloric acid (pH of 2) The crude product was crystallized from ethanol Product: 55.24 g (90.5%). ½ NR (270 MHz, CH30H-d4) d ppm 6.14 (d, J = 15.83 Hz, 1 H) 7.11-7.16 (m, 2 H) 7.68 (d, J = 16.36 Hz, 1 H); MS 233.1 (M-H) + HPLC Purity) 94%. INTERMEDIARY 48 (2E) -3- (5- bromothien-2-yl) acryloyl azide Se. added thionyl chloride (1.04 mL) to a solution of (2E) -3- (5-bromothien-2-yl) acrylic acid (1.04 g, 4.6 mmol) in chloroform (20 mL) and the mixture was refluxed 2 hours at 75 ° C and then used in the next stage. The above solution was added dropwise to a stirred suspension of sodium azide (0.58 g, 8.93 mmol), dioxane (3 mL) and water (3 mL) in an ice bath. After 10 minutes a precipitate appeared, which was separated by filtration and washed with water. The residue was dissolved in dichloromethane, dried with MgSC, filtered and the solvent was removed to give: 0.96 g (83.4%).

¾ NMR (270 MHz CH3OH-d) d ppm 6.20 (d, J = 15.57 Hz, 1 H) 7.15-7.25 (m, 2 H) 7.80 (d, J = 15.57 Hz, 1 H); MS 258.1 (M-H) +; 1 Purity (HPLC) 65%. INTERMEDIARY 49 2- bromothieno [3,2-c] pyridin-4- (5H) -one A solution of (2E) -3- (5-bromothien-2-yl) acryloyl azide (18.00 g, 69.7 mmol) resuleta in dichloromethane (100 ml) was added dropwise in diphenyl ether (90 ml) at 150 ° C. The temperature was increased to 220 ° C for 1 hour. The mixture was cooled to room temperature followed by the addition of ether. The solid precipitated and separated by filtration. Product: 13.58 g (84.6%). ¾ NMR (270 MHz, DMS0-d6) d ppm 6.82 (d, J = 7.13 Hz, 1 H) 0 7.27 (d, J = 6.86 Hz, 1 M 7.54 (s, 1 H) 11.55 (s, 1 H) MS 230.1 (M-M) +; Purity (HPLC) 92% INTERMEDIARY 50 2- bromine-4-chloro-thieno [3,2-c] pyridine Phosphorus oxychloride (4.08 g, 26.6 mmol) was added dropwise. ) to 2-bromothieno [3,2-c] pyridin-4- (5H) -one (2.04 g, 8.87 mmol) at 0 ° C. The mixture was heated at 135 ° C for 2.5 hours, then carefully poured over The precipitate was collected by filtration and dried to yield 1.78 g (80.7%) of the title product INTERMEDIARY 51 AND INTERMEDIARY 52 Chloride of 4-chlorothieno [3,2-c] pyridin-2-sulfonyl chloride and 2-bromo-chlorothieno [3, 2-c] pyridin-3-sulfonyl n-Butyl lithium (1.5 ml, 2.4 mmol) was added to 2-bromo-4-chlorothieno [3, 2-c] pyridine (0.5 g, 2 mmol) dissolved in dry THF (15 ml) at -78 ° C under nitrogen The mixture was stirred for 40 minutes The above solution was added to dry ether saturated with S02 (g. as) at -78 ° C. The mixture was warmed to room temperature, followed by the addition of ether. The precipitate was separated by filtration. The two title products were obtained and taken for the next step without further purification as follows: N-chlorosuccinimide (2.07 g, 1.03 mmol) was added to [(4-chlorothieno [3, 2-c] pyridin-2-yl. ) sulfonyl] lithium and [(2-bromo-4-chlorothieno [3,2- c] pyridin-3-yl) sulfonyl] lithium in dichloromethane (150 ml) at 0 ° C. The mixture was heated at 60 ° C for 2 hours, extracted with water (3 x 50 ml). The organic phase was separated, dried with MgSO 4, filtered and the volatile materials were removed by vacuum distillation. The crude products were used in the next step without further purification. INTERMEDIARY 53 AND INTERMEDIARY 54 P-Tolylamide 4-chloro-2-thieno acid [3, 2-c] pyridine-2-sulphonic acid and pa-tolylamide 2-bromo-4-chloro-thieno [3,2-c] pyridine-3-sulfonic acid p-Toludine (30 mg, 2.87 mmol) was added to solution of 4-chlorothieno [3, 2-c] pyridin-2-sulfonyl chloride and 2-bromo-4-chlorothieno [3,2-c] pyridin-3-sulfonyl chloride (0.07 g, 0.26 mmol) in dichloromethane and pyridine (0.19 ml). The reaction was stirred at room temperature for 2 hours. The solvent was removed and the crude mixture was taken for the next step without further purification. EXAMPLE 41 AND EXAMPLE 42 p-Tolylamide hydrochloride 4- (4-methyl-piperazin-1-yl) -thieno [3, 2-cjpyridine-2-sulphonic acid and 2-bromo-4-p-tolyl amide hydrochloride 4- methyl-piperazin-1-yl) -thieno [3,2-c] pyridine-3-sulphonic acid. It was heated at 100 ° C overnight, a mixture of p-tolyl amide 4-chloro-2-thieno [3]. , 2-c] pyridine-2-sulfonic acid and p-tolylamide 2-bromo-4-chloro-thieno [3,2-c] pyridine-3-sulfonic acid (70 mg, 0.21 mmol) in DMSO (2 ml), 1- methyl piperazine (0.344 ml, 3.1 mmol) and K2CO3 (28.5 mg, 0.21 mmol). The reaction mixture was dissolved in water and extracted with ethyl acetate (3 x 10 mL). The organic layers were collected and the solvent was removed. The products were purified by HPLC to give 1.9 mg of p-tolylamide acid 4- (4-methyl-piperazin-1-yl) -thieno [3,2-c] pyridine-2-sulfonic acid. The free base was converted to the hydrochloride salt by treatment with HCl in ether.

¾ NMR (270 MHz, Methanol-d) d ppm 2.26 (s, 3H) 2.98 (s, 3 H) 3.40-3.55 (m, 8 H) 7.02-7.10 (m, 6 H) 7.55 (d, J = 5 81 Hz, 1 H) 7.69 (s, 1 H) 8.13 (d, J = 5.81 Hz, 1 H); LC-MS 403 (M + H) +; Purity (LC-MS) 92% and 3.8 mg of p-tolylamide acid 2-bromo-4- (4-methyl-piperazin-1-yl) -thieno [3,2-c] pyridine-3-sulfonic acid. free was converted to the hydrochloride salt by treatment with HC1 in ether. ½ NMR (270 MHz, Methanol-d) d ppm 2.21 (s, 1 H) 3.00 (d, 3 H) 3.5 0-3.77 (m, 8 H) 7.00-7.10 (m, 6 H) 7.63 (d, J = 5.81 Hz, 1 H) 8.19 (d, J = 5.81 Hz, 1 H); LC-MS 481 (M + H) +; Purity (LC-MS) 98%. Reaction of sulfonyl chloride with amines (Method H) To a solution of the amine (1.3 equivalents) and pyridine (8 equivalents) in DCM was added the sulfonyl chloride (1 equivalent) and the reaction mixture was stirred overnight. After addition of Trisamide ™ (approximately 2 equivalents), the mixture was gently stirred for an additional 3 hours. The suspension was then filtered through a short plug of silica by the aid of DCM and ethyl acetate. The solvent was evaporated and the residue was dissolved in DCM and washed with 1M aqueous HCl solution (2 times). The combined organic phases were dried (MgSCv), filtered, and the solvent was removed to give the sulfonamide product. In cases of low purity material, the products were purified by flash column chromatography. The products were used in the next step (Procedure B). Coupling with Aromatic Amines (Method I) To the reaction mixtures of Method H, dissolved in DMSO (2 mL), amines (15 equivalents) and K2CO3 (1 equivalent) were added. The reactions were stirred at 100 ° C for 24 hours and then concentrated. The products were purified by LC-MS. Solvents were removed in vacuo by SpeedVac and purified by preparative LC / MS. Products that were not sufficiently pure (purity <90% were purified by preparative chromatography using gradients of acetonitrile-water containing 0.1% trifluoroacetic acid.) After HPLC analysis the fractions that were> 90% pure were collected and The deprotection of the amine in the piperazine was carried out by first dissolving the substance in methanol and adding portions of 1M HC1 / ether.The reactions were analyzed by TLC.The solvents were concentrated in vacuo by means of a SpeedVac.Deprotection of the BOC group (Method L) The sulfone or sulfonamide derivative (prepared by Methods H and I) were dissolved in a small amount of MeOH / DCM 1: 1 and treated with an excess of 1 M HCl in diethyl ether. The whole night atmosphere resulted in a precipitate that was collected by filtration to give the products as their corresponding hydrochloride salts. 4- (4-methylpiperazin-1-yl) -N-phenylthieno [3,2-c] pyridin-2-sulfonamide idrate The synthesis was carried out essentially as described in Methods H-L. Product: 8.1 mg (33.8%). ½ NMR (270 MHz, C¾OH-d4) 5 ppm 8.13 (d, J = 5.81 Hz, 1 H) 7.67 (s, 1 H) 7.54 (d, 1H) J = 5.81 Hz 1 H) 7.55-7.53 (ra, 5H) 2.97 (s, 3 H) (4H obscured by the solvent signal); LC-MS 389 (M-H); Purity (HPLC) 100%. EXAMPLE 44 (3-Fluoro-5-trifluoromethyl-denyl) amide hydrochloride 4-piperazin-1-ylthieno [3, 2-c] pyridine-2-sulphonic acid 4- [2- (3-fluorine - 5- trifluoromethyl-phenylsulfamoyl) -thieno [3,2-c] pyridin-4-yl] -piperazine-1-carboxylic acid and tert-butyl ester (0.235 mmol, 1 equiv.) As thienopyridine in Method HL. Product: 25.7 mg HPLC tR = 3.395 (System 5% to 50% ACN in 3 minutes, C8), Purity: 100%, LC / MS: tR = 1.375 (System: 30% to 60% ACN in 1.5 min, Hypersil BDS), Purity: 99% MS: 461 (M + l).

½ MR (270 ???, CH3OH-d4) d ppm 3.47 (m, 4 H) 3.53 (s, 1 H) 3.87 (m, 4 H) 7.21 (m, 1 H) 7.29 (m, 1 H) 7.33 (s, 1 H) 7.66 (d, J = 6.33 Hz, 1 H). EXAMPLE 45 (4-Chloro-phenyl) -amide 4-piperazin-1-ylthieno [3,2-c] pyridin-2-sulfonic acid hydrochloride (3-fluoro-5-trifluoromethyl-phenyl) - 4-chloro-thieno [3,2-c] pyridine-2-sulfonic acid (0.208 mol, 1 equiv.) as to thienopyridine in Methods HL. Product: 7.2 mg HPLC: tR = 3.039 (System: 5% to 50% ACN in 3 minutes, C6); Purity: 100%, LC / MS: tR = 0.905 (System: 30% to 60% ACN in 1.5 minutes, Hypersil BDS), Purity: 97%. MS: 409 (M + l). LE NMR (270 MHz, CH 3 OH-d) d ppm 3.50 (m, 4 H) 3.91 (m, 4 H) 7.25 (m, 4 H) 7.71 (dd, J = 6.33, 0.53 Hz, 1 H) 7.96 (d , J = 0.79 Hz, 1 H) 8.04 (d, J = 6.33 Hz, 1 H). EXAMPLE 46 (4-Isopropyl-phenyl) amide 4-piperazin-1-ylthieno [3,2-c] pyridine-2-sulphonic acid hydrochloride (4- isopropyl-phenyl) -amide 4-chloro acid -tiene [3,2-c] pyridine-2-sulfonic acid (0.201 mol, 1 equiv.) as thienopyridine in Method HL. Product: 6.9 mg HPLC: tR = 3.255 (System: 5 to 50% of ACN in 3 minutes, C8), Purity: 95%, LC / MS: tR = 1.255 (System: 30 to 60% of ACN in 1.5 minutes, Hypersil BDS), Purity: 98 S.

MS: 417 (M + 1). ½ MR (270 MHz, CH3OH-d4) d ppm 1.18 (d, J = 6.86 Hz, 6 H) 2.83 (m, 2 H) 3.52 (m, 4 H) 4.00 (m, 4 H) 7.14 (m, 3 H) 7.75 (d, J = 6.60 Hz, 1 H) 8.02 (m, 1 H). EXAMPLE 47 P-Tolylamide 4-piperazin-1-ylthieno [3,2-c] pyridine-2-sulphonic acid hydrochloride To a solution of 4-chloro-thieno [3,2-c] pyridin-2-chloride. Sulfonyl (0.640 g, 2.39 mmol) in DCM (20 mL) was added pyridine (1.9 mL, 23.9 mmol) followed by p-tolylamine (0.307 g, 2.86 mmol). The reaction mixture was stirred at room temperature b for 16 hours. The mixture was concentrated and re-dissolved in DMSO (10 mL), piperazin-1-carboxylic acid terbutilic ester (1.34 g, 7.17 mmol) and K2CO3 (0.989 g, 7.17 mmol) were added. The mixture was stirred at 100 ° C for 16 hours and then concentrated. The crude reaction mixture was dissolved in EtOAc (100 mL) and washed with brine (2 x 50 mL) =. The organic phase was dried (Na2SC > 4) and concentrated. The crude intermediate was purified by column chromatography on silica using EtOAc / n-pentane (1: 1) as eluent. The intermediate was dissolved in EtOAc / MeOH and diethyl ether saturated with HC1 (g) was added. The mixture was stirred at room temperature for 16 hours. The precipitate was collected by filtration and washed with diethyl ether / n-pentane to give 0.475 of the crude product. Purification by preparative inverted phase HPLC gave 0.133 g of the pure product:? NMR (DMSO-ds), 25 ° C, 270.17 MHz) d 10.61 (br s, 1H), 9.23 (br s, 2H), 8.13 (d, J = 5.80 Hz, 1H), 7.91 (s, 1H); 7.67 (d, J = 5.80 Hz, 1 H), 7.09-7.07 (m, 4H), 3.68-3.59 (m, 4H), 3.33-3.22 (m, 4H), 2.20 (s, 3H); m / z (posESI) 399 (M + H). EXAMPLE 48 4- (4-Methylpiperazin-1-yl) -N- (2-cyclohex-1-en-1-ylethyl) thieno [3,2-c] pyridin-2-sulfonamide hydrochloride The synthesis was carried out essentially as is described in the HL Method. Product 25.6 mg. ¾ NMR (270 MHz, DMSO-d6) d ppm 10.49-10.48 (ra, 1H) 8. 23-7.95 (m, 3H) 7.72-7.71 (m, IH) 5.34-5.33 (m, 1H) 4.14-4.11 (m, 2H) 3.53-3.51 (m, 2H) 3.29-3.25 (mr 2H) 2.98-2.97 (m, 2H) 2.85 (s, 3H) 2.04-1.81 (m, 4H) 1.57-1.15 (m, 8H); LC-MS 420.17 (M-H) +; Purity (LC-MS) 97%. EXAMPLE 49 2- (4- (4- Methylpiperazin-1-yl) thieno [3,2-c] pyridin-2-ylsulfonyl) -1,2,3,4-tetrahydroisoquinoline hydrochloride The synthesis was carried out essentially as described in the HL Method. Product: 15.5 mg. 1H NMR (270 MHz, DMSO ~ d5) d ppm 10.49-10.48 (m, 1H) 8.17-8.15 (m, 1H) 7.86-7.85 (m, 1H) 7.70-7.65 (m, 2H) 7.28-7.12 (m, 3H) 3.97-3.94 (m, 2H) 3.87-3.85 (m, 2H) 3.25-3.18 (, 2H) 2.84 (s, 3H) 1.67-1.65 (m, 2H) 3.51-3.34 (6H obscured by the signal of the solvent); LC-MS 428.13 (M-H) +; Purity (LC-MS) 99%. EXAMPLE 50 4- (4- Methylpiperazin-1-yl) -N- (2-thien-2-yl) thieno [3,2-c] pyridin-2-sulfonamide hydrochloride The synthesis was carried out essentially as described in HL method. Product: 29.5 mg. ¾ (270 MHz, DMSO-d6) d ppm 10.28-10.27 (m, 1H) 8.34-8.33 (m, 1H) 8.19-8.17 1H) 8.01-8.00 (m, 1H) 7.71-7.69 (ra, 1H) 7.31- 7.30 (m, 1H) 6.91-6.87 (m, 1H) 4.13-4, (m, 2H) 3.53-3.51 (m, 2H) 3.29-3.25 (m, 2H) 3.17-3.16 (m, 2H) 2.99-2.95 (m 4H) 2.86 (s, 3H); LC-MS 422.09 (M-H) +; Purity (LC.MS) 99%. EXAMPLE 51 Hydrochloride of 4-. { 4- methylpiperazin-1-yl) -N- [1- (1-naphthyl) ethyl] thieno [3,2-c] pyridin-2-sulfonamide The synthesis was carried out essentially as described in Method H-L. 20.1 mg. ¾ NMR (270 MHz, DMSO-d6) d ppm 10.28-10.27 (m, 1H) 8.85-8.84 (m, 1H) 8.02-8.01 (m, 7.67-7.60 (m, 4H) 7.53-7.50 (m, 2H) 7.39-7.36 (m, 2H) 4.72-4.70 (m, 1H) 3.87-3.84 1H) 3.72-3.70 (m, 1H) 3.23-3.13 (m, 4H) 2.84 (s, 3H) 1.42-1.40 (m 3H); LC-MS 466.15 (M-H) +; Purity (LC-MS) 99%. EXAMPLE 52 4- (4-Methylpiperazin-1-yl) -N- (4-hexylphenyl) thieno [3,2-c] pyridin-2-sulfonamide hydrochloride The synthesis was carried out essentially as described in Method H-L. 8.0 mg. XH NR (270 MHz, DMS0-d6) d ppm 10.39-10.38 (m, 1H) 8.16-8.15 (m, 1H) 7.90-7.89 (m, 1H) 7.66-7.65 (m, 1H) 7.09-7.08 (m, 4H) 4.00-3.98 (m, 2H) 3.51-3.48 (m, 2H) 3.26-3.22 (2H) 2.85 (s, 3H) 2.49-2.45 (m, 2H) 1.48-1.46 (m, 2H) 1.24-1.22 (m, 2H) m, 8H) 0.82-0.81 (m, 3H); LC-MS 472.20 (M-H) +; Purity (LC-MS) 98%. EXAMPLE 53 N- (3-chlorobenzyl) -4- (4-methyl-piperazin-1-yl) thieno [3,2-c] pyridin-2-sulfonamide hydrochloride The synthesis was performed essentially as described in Method H-L. 30.7 mg. 1 H NMR (270 MHz, DMSO-d 6) d ppm 10.25-10.24 (m, 1H) 8.78-8.77 (m, 1H) 8.18-8.17 (m, 1H) 7.91-7.90 (m, 1H) 7.68-7.67 (m, 1H) 7.26-7.19 (m, 3H) 4.21-4.20 (m, 2H) 4.08-4.05 (m, 2H) 3.54-3.51 (m, 2H) 3.28-3-23 (m, 2H) 2.87 (s, 3H) 2.84-2.60 (2H obscured by the solvent signal); LC-MS 436.08 (M-H) +; Purity (LC-MS) 94%. EXAMPLE 54 4- (4-Methylpiperazin-1-yl) -N- [1- (4-fluorophenyl) ethyl] thieno [3,2-c] pyridin-2-sulfonamide hydrochloride The synthesis was carried out essentially as described in the HL Method. 32.9 mg. XH MR (270 MHz, DMSO-d6) d ppm 10.16-10.15 (m, 1H) 8.75-8.73 (m, 1H) 7.63-7.62 (m, 2H) 7.25-7.24 (m, 2H) 6.91-6.88 (m, 2H) 4.58-4.55 (m, 1H) 4.02-3.95 (m, 2H) 3..55-3.53 (m, 2H) 3.25-3-21 (m, 2H) 2.68 (s, 3H) 1.31-1.30 (m , 3H) 2.70-2.64 (2H obscured by the solvent signal); LC-MS 434.12 (M-H) +; Purity (LC-MS) 92%. EXAMPLE 55 N- (2, 3-difluorobenzyl) -4- (4-met lpiperazin-1-yl) thieno [3,2-c] pyridin-2-sulfonamide hydrochloride The synthesis was carried out essentially as described in the Method HL. 26.7 mg. ½ NMR (270 MHz. DMSO-d6) d ppm 10.36-10.35 (m, 1H) 8.82-8.81 (m, 1H) 7.96-7.95 (m, 1H) 7.69-7.68 (mf 1H) 7.27-7.10 (m, 2H ) 4.26-4.25 (m, 2H) 4.11-4.08 (m, 2H) 3.54-3.52 (m, 2H) 3.28-3-24 (m, 2H) 2.68 (s, 3H) 2.86-2.60 (2H obscured by the signal of the solvent); LC-MS 438.10 (M-H) +; Purity (LC-MS) 93%. EXAMPLE 56 4- (4-Methylpiperazin-1-yl) -N- (4-chloro-2,5-dimethoxyphenyl) thieno [3f2-c] pyridn-2-sulfonamide hydrochloride The synthesis was carried out essentially as described in HL method. 14.6 mg. H NMR (270 MHz, DMS0-d6) d ppm 10.27-10.26 (m, 1H) 10. 14-10.13 (m, 1H) 8.18-8.17 (m, 1H) 7.83-7.82 (m, 1H) 7.69-7.68 (m, 1H) 7.09-7.07 (m, 2H) 4.00 (s 2H) 3.76-3.75 (m , 2H) 3.51-3.48 (m, 2H) 3.24-3.22 (m, 2H) 2.85 (s, 3H); LC-MS 482.08 (M-H) +; Purity (LC-MS) 95%. EXAMPLE 57 2- bromo-4- (4-methyl-piperazin-1-yl) -N- (2-cyclohex-1-en-1-ylethyl) -thieno [3,2-c] pyridine-3-sulfonamide hydrochloride. the synthesis essentially as described in the HL Method. 4.6 mg. lR NMR (270 MHz, DMSO-d6) d ppm 10.30-10.29 (m, 1H) 8.31-8.27 (m, 2H) 7.89-7.88 (m, 1H) 5.27-5.26 (m, 1H) 3.68-3.52 (m, 4H) 3.05-3.04 (m, 2H) 2.88-2.87 (m, 3H) 2.04-2.03 (m, 2H) 2.77-1.81 (m, 2H) 1.54-1.15 (m, 10H); LC-MS 498.09 (M-H) +; Purity (LC-MS) 93%. EXAMPLE 58 2- [2-Bromo-4- (4-methyl-piperazin-1-yl) -benzo [bichlophene-3-sulfonyl] -1,2,4,4-tetrahydro-isoquinoline hydrochloride The synthesis was essentially carried out as described in the HL Method. Product 3.7 mg. XH MR (270 MHz, DMSO-d6) 3 ppm 10.30-10.29 (m, 1H) 9.24-9.22 (m, 1H) 8.09-8.08 (m, 1H) 7.67-7.35 (m, 7H) 4.69-4.66 (m, 1H) 2.86-2.85 (m, 3H) 1.50-1.48 (m, 3H) 3.23-2.51 (8H obscured by the solvent signal); LC-MS 544.06 (M-H) +; Purity (LC-MS) 92%. EXAMPLE 59 2- bromo-4- (4-methyl-piperazin-1-yl) -N- [1- (4-fluorophenyl) et-2-yl] -thieno [3,2-c] pyridine-3-sulfonamide hydrochloride performed the synthesis essentially as described in Method HL. 4.3 mg. ½ NMR (270 MHz, DMS0-d6) d ppm 10.35 - 10.34 (m, 1H) 9.16-9.14 (m, 1H) 8.23-8.22 (m, 1H) 7.80-7.79 (m, 1H) 7.26-7.25 (m, 1H) 4.55-4.52 (m, 1H) 3.54- 3.52 (m, 2H) 2.88-2.87 (m, 3H) 1.38-1.36 (m, 3H) 3.17-2.83 (6H, obscured by the solvent signal); LC-MS 512.04 (M-H) +; Purity (LC-MS) 93%. EXAMPLE 60 2- bromo-4- (4-methyl-piperazin-1-yl) -N- (4-chloro) - (2,5-dimethoxyphenyl) thieno [3,2-c] pyridin-3-sulfonamide hydrochloride. the synthesis essentially as described in the HL Method. Product: 0.7 mg, LC-MS 561.91 (M-H) +; Purity (LC-MS) 95%.

EXAMPLE 61 N- (3,4-Dichlorophenyl) -4- piperazin-1-ylthieno [3,2-c] pyridin-2-sulfonamide hydrochloride 3,4-dichloroaniline (0.49 mmol) was dissolved in acetonitrile (1 mL) and pyridine (0.440 mL, 4.03 mmol) was added to a solution of 4-chlorothieno [3,2-c] pyridin-2-sulfonyl chloride (0.445 mmol) dissolved in acetonitrile (1 mL). The reaction was stirred for 1 hour, it was controlled with HPLC and the solvent was removed. The crude product was used in the next step without further purification. To the reaction mixture of the previous step, dissolved in DMSO (1 ml), piperazine (15 equiv.) And K2CO3 (1 equiv.) Were added. The reaction was stirred at 100 ° C for 24 hours and then concentrated. The product was purified by LC-MS and gave 5.8 mg (2.6%) of the title product. 1 H NMR (270 MHz, C¾OH-d 4) d ppm 8.07-8.05 (m, 2 H) 7.73 (d, J = 6.60 Hz, 1 H) 7.46-7.41 (m, 2 H) 7.16 (dd, J = 8.71, 2.38 Hz, 1 H) 3.94-3.90 (m, 4 H) 3.92 (m, 4 H) 3.53-3.50 (m, 4 H); LC-MS 443 (M-H) +; Purity (HPLC) 95%. EXAMPLE 62 N- (2,4-difluorophenyl) -4- piperazin-1-ylthieno [3,2-c] pyridin-2-sulfonamide hydrochloride The synthesis was carried out essentially as described in Method H-L. Product: 4.3 mg (2.1%).

½ NMR (270 MHz, C¾OH-d 4) d ppm 8.22 (s, 1 H) 8.07-8.01 (m, 2H) 7.79-7.72 (m, 1H) 7.55-7.47 (m, 1H) 7.04-6.94 (m, 2H ) 4.00-3.96 (m, 4H) 3.53-3.43 (m, 4H) 2.66 (s, 1H); LC-MS 411 (M-H) +; Purity (HPLC) 98%. EXAMPLE 63 4- Piperazin-1-yl- N- [3- (trifluoromethyl) phenyl] thieno [3,2-c] pyridin-2-sulfonamide hydrochloride The synthesis was carried out essentially as described in Method H-L. Product: 2.6 mg (1.2%). XE NMR (270 MHz, CH30H-d4) d ppm 8.05 (d, J = 6.60 Hz, 2H) 7.81-7.60 (m, 3H) 7.50 - 7.47 (m, 2H) 3.94- 3.90 (m, 4H) 3.56-3.49 (m, 4H) LC-MS 443 (MH) +; Purity (HPLC) 99 EXAMPLE 64 N- (3-Ethylphenyl) -4- piperazin-1-ylthieno [3,2-c] pyridin-2-sulonamide hydrochloride The synthesis was carried out essentially as described in Method H-L. Product: 1.4 mg (0.7%). NMR (270 MHz, CH3OH-d4) d ppm 8.35 (s, 1H) 7.58-6.92 (m, 7H) 3.54-3.44 (m, 2H) 3.01-2.95 (m, 4H) 2.66 (s, 1H) 2.18- 2.01 (m, 3H); LC-MS 403 (M-H) +; Purity (HPLC) 100%. EXAMPLE 65 N- (3,4-Dimethoxyphenyl) -4-piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonamide hydrochloride The synthesis was carried out essentially as described in Method H-L. product 7.7 mg (3.6%). ¾ NMR (270 MHz, CH30H-d4) d ppm 8.04 (d, J = 6.60 Hz, 1H) 7.77-7.75 (m, 2H) 6.85-6.83 (m, 2H) 6.68-6.83 (m, 1H) 3.87 - 3.85 (m, 4H) 3.77-3.75 (m, 6H) 3.49- 3.45 (m, 4H) 2.65 (s, 1H); LC-MS 435 (M-H) +; Purity (HPLC) 98%. EXAMPLE 66 N- (Bromo-2-methylphenyl-4-piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonamide hydrochloride The synthesis was carried out essentially as described in Method HL Product: 12.2 mg ( 5.3%) ¾ NMR (270 MHz, CH30H-d4) d ppm 8.07 (d, J = 6.33 Hz, 1H) 7.86 - 7.79 (m, 2H) 7.40 (d, J = 1.56 Hz, 1H) 7.30 -7.29 ( m, 1H) 7.08 (d, J = 8.71 Hz, 1H) 3.96 - 3.92 (m, 4H) 3.53 - 3.51 (4H) 2.66 (s, 1H) 2.11 (s, 3H; LC-MS 467 (M-H) +, Purity (HPLC) 90% EXAMPLE 67 2- ({4-piperazin-1-yl-thieno [3,2-c] pyridin-2-sulfonyl) -1,2,3,4-tetrahydrochloride Isoquinoline The synthesis was carried out essentially as described in Method HL from 4- [2- (3,4-dihydro-1H-isoquinoline-2-sulfonyl) -thieno [3,2-c] tert-butyl ether] ] pyridin-4-yl] -piperazine-1-carboxylic acid (0.235 mmol, 1 equiv.) Product: 4.0 mg LC / MS: tR = 0.801 (System: 30% to 60% ACN in 1.5 minutes, Hypersil BDS ), Purity: 92. MS: 415 (M + 1) 1 H NMR (270 MHz, DMS0-d6) d ppm 2.87 (t, J = 5.81 Hz, 2 H) 3.30 (s, 4 H) 4.43 (s, 2 H) 7.15 (m, 4 H) 7.70 (d, J = 5.54 Hz, 1 H) 8.12 (s, 1 H) 8.18 (d, J = 5.54 Hz, 1 H) 6 aliphatic protons were obscured by the water peak in the spectrum and thus could not be analyzed. EXAMPLE 68 2- (2-thiophene-2-yl-ethyl) -amide 4- piperazin-1-ylthieno [3,2-c] pyridin-2-sulphonic acid hydrochloride The synthesis was carried out essentially as described in the Method HL from 4- [2- (2-thiophene-2-yl-ethylsulfamoyl) -thieno [3,2-c] pyridin-4-yl] -piperazine-1-carboxylic acid tert-butyl ester (0.235 mmol, 1 equiv.). Product: 8.7 mg. LC / MS: tR = 0.430 (System: 30% to 60% ACN in 1.5 min, Hypersil BDS), Purity: 93%. MS: 409 (M + l). 1 H NMR (270 MHz, DMS0-d 6) 3 ppm 2.25 (s, 1 H) 2.75 (s, 1 H) 2.96 (t, J = 6.99 Hz, 1 H) 3.16 (q, J = 6.51 Hz, 1 H) 3.31 (s, 4 H) 3.70 (s, 4 H) 6.90 (m, 1 H) 7.32 (t, J = 5.54 Hz, 1 H) 7.70 (d, J = 5.81 Hz, 1H) 8.04 (d, J = 1.85 Hz, 1 H) 8.18 (d, J = 5.54 Hz, 1 H) 8.36 (ni, 1 H) 9.05 (s, 1 H).

EXAMPLE 69 (4- Chloro-2, 5-dimethoxyphenyl) -amide 4- piperazin-1-ylthieno [3,2-c] pyridine-2-sulfonic acid hydrochloride The synthesis was carried out essentially as described in the Method HL from 4- [2- (4-chloro-2,5-dimethoxy-phenylsulfamoyl) -thieno [3,2-c] pyridin-4-yl] -piperazine-1-carboxylic acid tert-butyl ester (0.112) mmoles, 1 equiv.), which was used as thienopyridine in Method C. Product: 14.7 mg. LC / MS: tR = 0.610 (System: 30% to 60% ACN in 1.5 minutes, YMC), Purity: 92%. MS: 469 (M + 1). 1 H NMR (270 MHz, DMSO-ds) d ppm 3.17 (s, 1 H) 3.27 (s, 4H) 3.38 (s, 3 H) 3.58 (d, J = 4.22 Hz, 4 H) 3.77 (s, 3 H) 7.08 (s, 1 H) 7.69 (d, J = 5.81 Hz, 1 H) 7.81 (s) , H) 8.16 (d, J = 5.81 Hz, 1 H) 9.07 (s, 1 H) 10.17 (s, 1 H). EXAMPLE 70 Phenethylamide-piperazin-1-yl-thieno [3,2-c] pyridin-2-sulfonic acid hydrochloride The synthesis was carried out essentially as described in the HL Method from the 4- tert-butyl ester (2- phenethylsulfamoyl-thieno [3, 2-c] pyridin-4-yl) piperazin-1-yl carboxylic acid (0.112 mmol, 1 equiv.). Product: 3.8 mg. LC / MS: tR = 0.410 (System: 30% to 60% ACN in 1.5 minutes, YMC), purity: 91%. MS: 403 (M + 1).

½ NMR (270 MHz, CH 3 OH-d 4) d ppm 1.44 (d, J = 7.13 Hz, 2 H) 3.51 (d, J = 4.75 Hz, 4 H) 3.54 (s, 2 H) 3.94 (m, 4 H) 7.05 (m, 4 H) 7.16 (m, 1 H) 7.62 (s, 1 H) 7.72 (d, J = 6.60 Hz, 1 H) 8.00 (d, J = 6.60 Hz, 1 H). EXAMPLE 71 (2,6-Diethyl-phenyl) -amide 4-piperazin-1-ylthieno [3,2-c] pyridin-2-sulfonic acid hydrochloride The synthesis was carried out essentially as described in the HL Method from 4- [2- (2,6-diethyl-phenylsulfamoyl) -thieno [3, 2-c] pyridin-4-yl] -piperazine-1-carboxylic acid tert-butyl ester (0.112 mmol, 1 equiv.) . Product: 9.0 mg. LC / MS: tR = 0.830 (System: 30% to 60% ACN in 1.5 minutes, YMC), Purity: 92%. MS: 431 (M + l). E NMR (270 MHz, DMSO-D6) d ppm 0.96 (t, J = 7.52 Hz, 6 H) 2.25 (m, 1 H) 2.43 (s, 2 H) 2.75 (t, J = 1.72 Hz, 1 H) 3.26 (s, 4 H) 3.62 (s, 4 H) 7.09 (s, 1 H) 7.12 (s, 1 H) 7.23 (m, 1 H) 7.73 (d, J = 5. 8 1 Hz, 1 H) 7.77 (s, 1 H) 8.19 (d, J = 5.81 Hz, 1 H) 9.04 (s, 1 H) 9.95 (s, 1 H). EXAMPLE 72 (3-Phenyl-propyl) -amide 4-piperazin-1-ylthieno [3,2-c] pyridin-2-sulfonic acid hydrochloride The synthesis was carried out essentially as described in Method HL from the ether 4- [2- (3-phenyl-propylsulfamoyl) -thieno [3,2-c] pyridin-4-yl] piperazine-1-carboxylic acid tert-butyl ester (0.112 mmol, 1 equiv.). Product: 13.0 mg. LC / MS: tR = 0.726 (System: 30% to 60% ACN in 1.5 minutes, YMC), Purity: 91%. MS: 417 (M + 1).

½ NMR (270 MHz, CH30H-d4) d ppm 1.82 (m, 2 H) 2.63 (m, 2 H) 3.04 (t, J = 6.86 Hz, 2 H) 3.55 (s, 4 H) 4.09 (s, 4 H) 7.16 (m, 4 H) 7.82 (d, J = 6.60 Hz, 1 H) 8.05 (d, J- = 6.33 Hz, 1 H) 8.14 (s, 1 H). EXAMPLE 73 Hydrochloric acid of (3, 3-diphenyl-propyl) -amide 4- piperazin-1-ylthieno [3,2-c] pyridine-2-sulfonic acid The synthesis was carried out essentially as described in Method HL from 4- [2- (3, 3-diphenyl-propylsulfamoyl) -thieno [3,2-c] pyridin-4-yl] piperazine-1-carboxylic acid tert-butyl ester (0.112 mmol, 1 equiv.). Product: 14.4 mg. LC / MS: tR = 1.109 (System: 30% to 60% ACN in 1.5 min, YMC, Purity: 93% MS: 493 (M + l). ¾ NMR (270 MHz, DMS0-d6) d ppm 2.20 (m, 2 H) 2.80 (m, 2 H) 3.29 (s, 4 H) 3.67 (d, J = 5.01 Hz, 4 H) 4.01 (m, 1H) 7.14 (m, 8 H) 7.71 (d, J = 5.81 Hz, 1 H) 7.95 (s, 1 H) 8.18 (d, J = 5.81 Hz, 1 H) 8.27 (m, 2 H) 9.13 (s, 2 H) EXAMPLE 74 [2- ( 5- methoxy-1H-indol-3-yl) -ethyl] -amide 4- piperazin-1-ylthieno [3,2-jpyridin-2-sulfonic acid The synthesis was carried out essentially as described in Method HL from the 4- {2- [2- (5-methoxy-1H-indol-3-yl) -ethylsulfamoyl} -thieno [3,2-c] pyridin-4-yl} - tert-butyl ester. piperazine-1-carboxylic acid (0.112 mmol, 1 equiv.) Product: 6.1 mg LC / MS: tR = 0.364 (System: 30% to 60% ACN in 1.5 minutes, YMC), Purity: 91 ¾. MS: 472 (M + 1) XH NMR (270 MHz, CH 3 OH-d) d ppm 2.85 (t, J = 6.20 Hz, 2 H) 3.48 (t, J = 6.20 Hz, 2 H) 3.55 (m, 4 H) 3.80 (s, 3 H) 4.02 (m, 4 H) 6.44 (dd, J = 8.71, 2.37 Hz, 1 H) 6.8 0 (m, 2 H) 6.97 (s, 1 H) 7.64 (s, 1 H) 7.67 (s, 1 H) 7.97 (d, J = 6.60 Hz, 1 H). EXAMPLE 75 4-Trifor-4-methyl-benzylamide-4-piperazin-1-ylthieno [3,2-c] pyridin-2-sulphonic acid hydrochloride The synthesis was carried out essentially as described in Method HL from the tert-butyl ester of the tert-butyl ester. 4- [2- (4-trifluoromethyl-benzylsulfamoyl) -thieno [3,2-c] pyridin-4-yl] -piperazine-1-carboxylic acid (0.112 mmol, 1 equiv.), which was used as thienopyridine in Method C. Product: 1.9 mg. LC / MS: tR = 0.771 (System: 30% to 60% ACN in 1.5 minutes, YMC), Purity: 91%. MS: 457 (M + 1).

½ NMR (270 MHz, C¾0H-d4) d ppm 3.54 (m, 4 H) 3.98 (m, 4 H) 4.36 (s, 2 H) 7.49 (m, 4 H) 7.74 (d, J = 6.86 Hz, 1 H) 8.02 (s, 1 H) 8.07 (d, J = 6.60 Hz, 1 H). EXAMPLE 76 4-Piperazin-1-thieno [3,2-c] pyridin-2-sulfonic acid benzyl-ethyl-amide hydrochloride The synthesis was carried out essentially as described in Method HL from the tert-butyl ester 4- [2- (Benzyl-ethyl-sulfamoyl) -thieno [3,2-c] pyridin-4-yl] piperazine-1-carboxylic acid (0.112 mmol, 1 equiv.). Product: 6.4 mg. LC / MS: tR = 0.930 (System: 30% to 60% ACN in 1.5 min YMC), Purity: 95%. MS: 417 (M + 1). ¾ NMR (270 MHz, CH3OH-d) d ppm 1.03 (t, J = 7.13 Hz. 3 H) 3.37 (m, 2 H) 3.57 (s, 2 H) 3.75 (m, 2 H) 4.11 (s, 2 H) 4.50 (s, 2 H) 5.80 (s, 1 H) 7.32 (m, 5 H) 7.84 (d, J = 6.60 Hz, 1 H) 8.07 (d, J = 6.60 Hz, 1 H) 8.14 (s) , 1 HOUR) . INTEEMEDIARY 55 4- (3- { [ { 3- ethylphenyl) amino] sulfonyl} thieno [3,2-c] pyridin-4-yl) piperazin-1-tert-butyl carboxylate Prepared from 4- [3- (chlorosulfonyl) thieno [3,2-c] pyridin-4-yl] piperazin- 1 - tert-butyl carboxylate (90.0 mg, 0.215 mmol) and 3- ethylamine (33.9 mg, 0.28 mmol) to give the title compound as an off-white solid (82.7 mg, 76%). ¾ NMR (400 MHz, CDC13) d 1.03 (t, J = 7.5 Hz, 3 H), 1. 48 (s, 9 H), 2.47 (q, J = 7.7 Hz, 2 H), 3.00-3.53 (m, 6 H), 4.02-4.44 (m, 2 H), 6.66 (d, J = 8.0 Hz, 1 H), 6.75 (s, 1 H), 6.66 (d, J = 8.0 Hz, 1 H), 7.02 (t, J = 7.8 Hz, 1 H), 7.67 (d, J = 5.5 Hz, 1 H), 8.24 (s, 1 H), 8.39 (d, J = 5.5 Hz, 1 H), 9.80 (s, 1 H). MS (ESI +) m / z 503.2 (M + H) +. HPLC 97%, RT: 3.93 min (5-99% MeCN for 3 min). EXAMPLE 77 N- (3-Ethylphenyl) -4- piperazin-1-ylthieno [3,2-c] pyridin-3-sulfonamide hydrochloride Prepared from 4- (3. {[[(3-ethylphenyl) amino] sulfonyl] .} tert-butyl thieno [3,2-c] pyridin-4-yl) piperazine-1-carboxylate (81.1 mg, 0.161 min) which produced 19 mg (98%) of the product as a white solid (38.0 mg, 54%). XH NMR (400 MHz, C¾0H-d4) d 1.09 (t, J = 7.5 Hz, 3 H), 2.51 (q, J = 7.5 Hz, 2 H), 3.59 (br.s, 8 H), 6.89-6.92 (m, 3 H), 7.12-7.14 (m, 1 H), 8.06 (d, J = 6.0 Hz, 1 H), 8.36 (d, J = 6.0 Hz, 1 H), 8.49 (s, 1 H) . MS (ESI +) m / z 403.2 (M + H) +. HPLC 95%, RT: 3.02 min (5-99% MeCN for 3 min).

INTERMEDIARY 56 4- (3-bromothieno [3,2-c] pyridin-4-yl) piperazin-1-yl-butyl carboxylate A mixture of 3-bromo-4-chlorothieno [3,2-c] pyridine ( 729 mg, 2.93 mmol), tert-butyl piperazine-1-carboxylate (1.64 g, 8.80 mmol) and K2CO3 (811 mg, 5.87 mmol) in DMSO (45 mL) was stirred for 5 days at 100 ° C. After addition of H20 and ethyl acetate, the layers were separated. The aqueous phase was extracted twice with ethyl acetate, and the combined organic phases were washed with water and brine and dried (MgSO4). After filtration and removal of the solvent, the residue was purified by flash chromatography on silica gel (pentane / ethyl acetate, 8: 2) to give the product as a white powder (398 mg, 34%, 99% by HPLC, RT: 3.27 min (5-99% MeCN for 3 minutes) ½ NMR (400 MHz, CH30H-d4) d 1.48 (s, 9H), 3.21 (br s, 4H), 3.71 (s br., 4H) , 7.61 (d, J = 6.1 Hz, 1H), 7.72 (s, 1 H), 8.08 (d, J = 5.6, ??). MS (ESI +) m / z 398.2 (M + H) +. INTERMEDIARY 57 { 4- [4- (tert-butoxycarbonyl) piperazin-1-yl] thieno [3, 2-c] pyridin-3-yl.] Sulfonyl) lithium To a suspension of 4- (3-bromothieno) [3, 2-c] pyridin-4-yl) piperazin-1-tert-butyl carboxylate (4055 g, 10.18 mmol) in diethyl ether (30 mL) at -78 ° C under N2 atmosphere, drop was added a 1.6 M solution of n-BuLi in hexane (9.5 ml, 15.2 mmol). After 1 hour of stirring, a saturated solution of S02 in THF (25 ml) at -78 ° C was transferred via cannula to the mixture. The reaction was left overnight, gradually increasing the temperature to the environment. The solvent was evaporated, and the residue was washed with several portions of diethyl ether and then dried in vacuo to give 4094 g of an off-white solid consisting of 66% of the title compound and 34% (n-butylsulfonyl) lithium as by-product. The mixture was used without any further purification in the next step. ¾ NMR (400 MHz, CH30H-d4) d 1.48 (s, 9 H), 3.22 (br.s, 4 H), 3.72 (s br., 4 H), 7.60 (d, J = 5.5 Hz, 1 H), 8.06 (d , J = 5.5 Hz, 1 H), 8.14 (s, 1 H). MS (ESI +) m / z 384.0 (M + H) +. HPLC RT: 2.62 min (5-99% MeCN for 3 min). INTERMEDIARY 58 4- [3- (Chlorosulfonyl) thieno [3,2-c] pyridin-4-yl] piperazin-1-tert-butyl carboxylate To a suspension of (. {4- [4- (tert-butoxycarbonyl) ) piperazin-1-yl] thieno [3,2-c] pyridin-3-yl.] sulfonyl) lithium (2751 g, 7.06 mmol (3.126 g of the crude product mixture)) in DCM (40 ml) 0 ° C N-succinimide (1338 g, 10.0 mmol) was added. After 20 minutes, the temperature was increased to room temperature, and the reaction mixture was stirred for an additional 2.5 hours. The resulting product solution was washed with water, and the aqueous phase was extracted with DCM. The combined organic extracts were washed with brine and dried over MgSO4. After filtration and evaporation of the solvent, the residue was washed with several portions of pentane to give the product as a whitish solid (2.024 g, 69%).

½ NMR (400 MHz, CH3OH-d4) d 1.47 (s, 9 H), 3.11 (br.s, 4 H), 3.2-4.3 (s br., 4 H), 7.68 (d, J = 5.5 Hz, 1 H), 8.45 (d, J = 5.5 Hz, 1 H), 8.60 (s, 1 H). MS (ESI +) m / z 418.2 (M + H) ÷. HPLC 92%, RT: 3.76 min (5-99% MeCN for 3 min). INTERMEDIARY 59 4- (3- { [(4-isopropylphenyl) amino] sulfonyl} thieno [3,2-c] pyridin-4-yl) piperazin-1-tert-butyl carboxylate Prepared from 4- [ 3- (Chlorosulfonyl) thieno [3,2-c] pyridin-4-yl] piperazin-1-tert-butyl carboxylate (90.0 mg, 0.215 mmol) and 4-isopropylaniline (37.9 mg, 0.28 mmol) to give the compound of the title as a whitish solid (58.3 mg, 52%). XE 3SSMR (400 MHz, CH3OH-d4) d 1.48 (s, 9 H), 3.22 (br.s, 4 H), 3.72 (s br., 4 H), 7.60 (d, J 5.5 Hz, 1 H) , 8.06 (d, J = 5.5 Hz, 1 H), 8.14 (s, 1 H). MS (ESI +) m / z 384.0 (M + H) +. HPLC RT: 2.62 min (5-99% MeCN for 3 min). EXAMPLE 78 N- (4-isopropylphenyl) -4- piperazin-1-ylthieno [3, 2-c] pyridine-3-sulfonamide hydrochloride Prepared from 4- (3. {[[(4- isopropylphenyl) amino] sulfonyl] .} thieno) [3,2-c] pyridin-4-yl) piperazine-1-carboxylate (60.0 mg, 0.116 mmol) which yielded 19 mg (98%) of the product as a white solid ( 25.8 mg, 49%) in accordance with the HL Method. XH NMR (400 MHz, CH3OH-d4) d 1.16 (d, J = 7.0 Hz, 6 H), 2.81 (sept., J = 6.8 Hz, 1 H), 3.59 (s, br., 8 H), 7.00 (d, J = 8.0 Hz, 2 H), 7.10 (d, J = 8.0 Hz, 2H), 8.07 (s, br., 1 H), 8.37 (s, br., 1 H), 8.50 (s, 1 HOUR) . MS (ESI +) m / z 417.2 (M + H) +. HPLC 94%, RT: 3.14 min (5-99% MeCN for 3 min.) EXAMPLE 79 N- (4-methylphenyl) -4- (pyrrolidin-3-yloxy) thieno [3,2-c] pyridine hydrochloride 2- Sulfonamide 4- Chloro- N- (4-methylphenyl) thieno [3,2-c] pyridine-2-sulfonamide (60.0 mg, 0.17 mmol) in dry DMF (1 mL) and NaH (5.1 mg, 0.21) were added. mmoles) to pyrrolidin-3-ol (18.5 mg, 0.21 mmol) under nitrogen. The mixture was heated in the microwave at 200 ° C in 5 minutes. The product was purified by preparative HPLC. Product: 29.9 mg (43.4%). ¾ NMR (270 MHz, CH3OH-d4) d ppm 8.09 (s, 1H) 7.71 (d, J = 6.93 Hz, 1 H) 7.46 (d, J = 6.93 Hz, 1 H) 7.47-7.44 (m, 4H) 4.67 (d, J = 3.22 Hz, 1 H) 3.97 (s, 2 H) 2.26 (s) , 3H). LC-MS 390 (M-H) +; Purity (HPLC) 99%. EXAMPLE 80 N- (4-methylphenyl) -4- (piperidin-4-yloxy) thieno [3,2-c] pyridin-2-sulfonamide hydrochloride The synthesis was carried out essentially as described for the N- hydrochloride compound. (4-methylphenyl) -4- (pyrrolidin-3-yloxy) thieno [3,2-c] pyridin-2-sulfonamide. Product: 16.2 mg (22.7%).

¾ NMR (270 MHz, CH3OH-d4) d ppm 7.81-7.78 (m, 2H) 7.62 (d, J = 6.93 Hz, 1 H) 7.13-7.04 (m, 4H) 4.05-3.94 (m, 1H) 3.90- 3.88 (m, 2H) 3.63-3.58 (m, 2H), 2.27 (s, 3H) 2.06-2.03 (m, 2H) 2.01-1.71 (m, 2H); LC-MS 404 (M-H) +; Purity (HPLC) 99%. EXAMPLE 81 N- (2,3-di luorobenzyl) -4-piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonamide hydrochloride Product: 74.4 mg (39.2%). ½ NMR (270 MHz, CH3OH-d4) d ppm 8.10-8.03 (m, 2H) 7.81 (d, J = 6.68 Hz, 1 H) 7.16-7.05 (m, 3H) 4.37 (s, 2 H) 4.11-4.07 (m, 4H) 3.59-3.53 (m, 4H); LC-MS 425 (M-H) +; Purity (HPLC) 90%. EXAMPLE 82 N- (3-chlorobenzyl) -4- piperazin-1-ylthieno [3,2-c] pyridin-2-sulfonamide hydrochloride Product: 74.4 mg (44.7%). LH NMR (270 MHz, CH30H-d4) d ppm 8.04-8.01 7.85 (d, J = 6.93 Hz, 1 H) 7.22-7.15 (m, 4H) 4.30 (s, 2 H) 4.14-4.10 (m, 4H) 3.60-3.54 (m, 4H); LC-, MS 423 (M-H) + Purity (HPLC) 90%.

Table 5 Reaction Scheme 6 Legends of Reaction Scheme 6: i) amines protected with BOC (R4), K2C03, DMSO ii) thiophenols (R1-SH), Cu2 (I) 0, DMF iii) NaOAc, ozone, water; iv) a.TFA, b.HCl, methanol. INTERMEDIARY 60 4- (2-Bromothieno [3,2-c] pyridin-4-yl) piperazine-1-carboxyl to tert -butyl 2-bromo-4-chlorothieno [3,2-c] pyridine (5.0 g, 20.4 mmol) and K2CO3 (13.97 g, 101.2 mmol) in DMSO (20 mL) followed by addition of tert-butyl piperazine-1-carboxylate (4.14 g, 22.26 mmol). The reaction mixture was stirred at 100 ° C for 6 days. The reaction mixture was filtered to remove the carbonate and then water (50 ml) and ethyl were added. The phases were separated and the aqueous phase was extracted with ethyl acetate. The crude product was purified by flash chromatography using ethyl acetate / hexane (2/8) as eluent to give 2 g of the desired product, 25.99% pure product. ½ NMR (270 MHz, CDC13) d 1.48 (s, 9H), 1.52-1.63 (m, 1H), 3.42-3.47 (m, 4H), 3.61-3.64 (m, 4H), 7.22 (dd, J = 5.4, 1 Hz, 1H), 7.35 (d, J = 1 Hz, 1H), 8.04 (d , J = 5.4 Hz, 1H). m / z = 398.91 (M + H) +, bromide standard. INTERMEDIARY 61 4- (2-bromothieno [3,2-c] pyridin-4-yl) -1,4-diazepane-1-tert-butyl carboxylate The same procedure as above was used starting from 2- bromo- 4- chlorothieno [3,2-c] pyridine (7.5 g, 30.45 mmol), K2C03 (6.7 g, 33.5 mmol) and tert-butyl 1- (4-diazepane-1-carboxylate) (21.0 g, 152.2 mmol) in DMSO (30 my) . Purification by flash chromatography gave 3.04 g of the title compound (Product, 25 ¾). Purity by HPLC, 92%; XE NMR (270 MHz, CDCl 3) d 1.38 (s, 4.5 H), 1.43 (5.4.4 H), 1.96-2.11 (m, 2 H), 3.36-3.41 (m, 1 H), 3.46-3.51 (m, 1 H), 3.65-3.87 (m, 6H), 7.02-7.04 (m, 1H), 7.40-7.42 (m, 1H), 7.94 (d, J = 5.4 Hz, 1 H). m / z = 411.9 7 (M + H) +. Coupling with thiophenols (Method M INTERMEDIARY 62 4- (2- phenylthio) thieno [3,2-c] pyridin-4-yl) -1,4-diazepane-1-tert-butyl carboxylate 4- (2- bromothieno [3,2-c] pyridin-4-yl) -1,4-diazepane-1-tert-butyl carboxylate (0.31 g, 0.752 mole), pulverized KOH (0.084 g, 1.5 mole) and Cu2 (I) 0 (0.1 g, 0.75 min) with DMF (1 mL) before the addition of a benzothiol solution (0.016 g, 1.5 mmol) in DMF (1 mL). The reaction mixture was heated at 120 ° C for 15 hours. The reaction mixture was poured into a plug of silica gel and eluted with chloroform, to give the crude product. The crude product was purified by flash chromatography using ethyl acetate / hexane (2/8) as eluent stop 0.21 g of the desired product, yield 64%, 90% pure. X H NMR (270 MHz, CDCl 3) d 1.37 (s, .5 H), 1.43 (s, 4.5 H), 1.97-2.10 (m, 2 H), 3.36-3.43 (m, 1 H), 3.46-3.53 (m, 1 H) ), 3.64-3.73 (m, 2H), 3.78-3.96 (m, 4H), 7.05 (d, J = 5.4 Hz, 1H), 7.22-7.32 (m, 5 H), 7.59-7.63 (m, 1H) , 7.97 (d, J = 5.4 Hz, 1 H). m / z = 442.15 (M + H) +. Oxidation of thio-derivatives (Method N) INTERMEDIARY 63 4- (2-phenylsulfonyl) thieno [3,2-c] pyridin-4-yl) -1,4-diazepane-1-tert-butyl carboxylate A solution of 4 - (2-phenylthio) thieno [3, 2-c] pyridin-4-yl) -1,4-diazepane-1-tert-butyl carboxylate (0.21 g, 0.48 mmol) and NaOAc (0.5 g) in ethanol ( 10 ml), (H ~ 5) followed by the addition of Oxona (0.64 g, 1. 04 immoles) dissolved in water (1 ml). The reaction mixture was stirred at RT for 16 hours. Additional Oxone (0.32 g) in water (1 ml) was added. The total conversion of the SM was obtained after 8 hours. Water (50 ml) and chloroform (30 ml) were added. The phases were separated and the aqueous phase was extracted with chloroform. The combined organic phases were dried over (MgSO4), the solvent was evaporated to give the crude product, which was purified by inverted phase chromatography (10-> 90), to give 0.191 g of the desired product as yellow oil (yield 86%) 98% pure. ½ MR (270 MHz, CDC13) d 1.28 (s, 4.5 H), 1.38 (s, 4. 5 H), 1.99-2.03 (m, 2 H), 3.31-3.40 (m, 1H), 3.42-3.47 (m, 1 H), 3.63-3.69 (m, 2H), 3.85-3.98 (m, 4H) , 7.02 (d, 3 = 5.4 Hz, 1H), 7.48-7.61 (m, 3H), 7.76-8.01 (m, 3H), 8.06-8.08 (m, 1H). m / z == 474.01 (M + H) +. Removal of the t-butyl carboxylate protecting group (Method O) EXAMPLE 83 4- (1, 4-Diazepan-1-yl) -2- (phenylsulfonyl) thieno [3,2-c] pyridine hydrochloride 4- was dissolved (2-phenylsulfonyl) thieno [3, 2-cjpyridin-4-yl] -1,4-diazepane-1-tert-butyl carboxylate (0.165 g, 0.348 mmol) in DCM (2 mL) and TFA ( 1 mi). The reaction mixture was stirred for 2 hours. The solvent was evaporated. Methanol and HCl in ether (x 3) were added to give 0.118 g of the desired HCl salt, yield 85%, 98% pure. ¾ NMR (270 MHz, C¾OH-d4) d 2.45-2.52 (m, 2H), 3.45- 3.52 (m, 2H), 3.70-3.79 (m, 2H) 9 4.18-4.22 (m, 2H), 4.30-4.40 (m, 2H), 7.62-7.76 (m, 5H), 7.91 (d, J = 5.4 Hz, 1H), 8.11 (dd, J = 5.4, 1 Hz, 1H), 8.41 (d, J = 1 Hz, 1 HOUR) . m / z 374.09 (M + H-HC1). INTERMEDIARY 64 4- [2- (4- tert-butylphenyl) thio] thieno [3, 2-c] pyridin-4-yl) -1,4-diazepane-1-tert-butyl carboxylate The product was prepared according to method M. Purification by flash chromatography using ethyl acetate / hexane (3/8) as eluent it gave 0.035 g, 99% pure. ¾ 1SIMR (270 MHz, CDC13) d 1.28 (s, 9H), 1.38 (s, 4.5 H), 1.43 (s, 4.5 H), 1.98-2.03 (m, 2H), 3.35-3.41 (m, 1H), 3.46-3.52 (m, 1H), 3.62-3.72 (m, 2H), 3.77-3.93 (4H), 7.04 (d, J = 5.4 Hz, 1H), 7.27-7.34 (m, 4H), 7.54-7.56 ( m, 1H), 7.95 (d, S = 5.4 Hz, 1H). m / z = 498.0 (M + H) +. INTERMEDIARY 65 4- [2- (4-tert-Butylphenyl) sulfonyl] thieno [3,2-c] pyridin-4-yl) -1,4-diazepane-1-tert-butyl carboxylate Procedure B from 4- [2- (4-tert-Butylphenyl) thio] thieno [3,2-c] pyridin-4-yl) -1,4-diazepane-1-carboxylic acid tert-butyl ester (0.035 g, 0.070 mmol), Oxona ( 0.17 g, 0.28 mmol), NaOAc (0.5 g) in EtOH (2 mL, followed by inverted phase chromatography (40? | 70) gave 6 mg of the product Yield 17%, 98% pure 1H * NMR (270 MHz , CDCl3) d 1.32 (s, 9H), 1.35 (s, 9H), 2.05-2.15 (m, 2H), 3.45-3.62 (m, 2H), 3.75-4.13 (m, 6H), 7.20-7.27 (m , SH), 7.58 (d, J = 10.8 Hz, 1H), 7.93 (d, J = 10.8 Hz, 1H) m / z = 530.0 (M + H) INTERMEDIARY 66 4- [2- (3, 4 - dimethylphenyl) thio] thieno [3, 2-c] pyridin-4-yl) -1,4-diazepane-1-tert-butyl carboxylate The title compound was obtained according to Method M. Purification by chromatography Flash using ethyl acetate / hexane (2/8) as eluent gave 0.022 g, 95% pure. XH NMR (270 MHz, CDC13) d 1.38 (s, 4.5 H), 1.43 (s, 4.5 H), 1.96-2.04 (m, 2 H), 2.21 (s, 3 H), 2.22 (s, 3 H), 3.37- 3.45 (m, 2H) 2 3.47-3.50 (m, 2H), 3.77-3.95 (m, 4H), 7.01-7.12 (m, 3H), 7.16 (s, 1 H), 7.5 3 (dd, J = 5.4 , 1 Hz, 1 H), 7.94 (d, J = 5.4 Hz, 1 H). m / z = 470.3 (M + H). INTERMEDIARY 67 4- [2- (3, 4-dimethylphenyl) sulfonyl] thieno [3,2-c] pyridin-4-yl) -1,4-diazepane-1-tert-butyl carboxylate Procedure B from 4- [2- (3, 4-dimethylphenyl) thio] thieno [3,2-c] pyridin-4-yl) -1,4-diazepane-1-carboxylic acid tert-butyl ester (0.022 g, 0.047 mmol) Oxone (O .l'l g, 0.19 mmoles); NaOAc (0.5 g) in EtOH (2 ml) followed by inverted phase chromatography (40-> 70), 9 mg of the product. Performance 38% r 92% pure. 2H NMR (270 MHz, CDC13) d 1.35 (s, 9H), 2.08-2.20 (m, 2H), 2.33 (s, 6H), 3.52-3.59 (m, 2H), 3.83-3.88 (m, 2H), 4.08-4.18 (m, -4H), 7.21-7.28 (m, 2H), 7.31-7.35 (m, 1H), 7.73-7.75 (m, 2H), 8.02 (d, J = 5.4 Hz, 1H). m / z = 502.21 (M + H). INTERMEDIARY 68 4- [2- (1-naphthyl) thio] thieno [3, 2-c] pyridin-4-yl) -1,4-diazepane-1-tert-butyl carboxylate The title compound was obtained in accordance with Method M. Purification by flash chromatography using ethyl acetate / hexane (2/8) as eluent gave 0.055 g. 99% purity by HPLC. ½ NMR (170 MHz, CDC13) d 1.37 (s, 4.5 H), 1.43 (s, 4. 5 H), 1.89-2.20 (m, 2H), 3.30- 3.40 (m, 1H), 3.43-3.50 (m, 1H), 3.60.3.90 (m, 6H), 6.99 (d, J- = 5.4 Hz, 1H), 7.39 (dd, J = 8.1, 1 Hz. 1 H), 7.50-7.61 (m, 5H), 7.79-7.88 (m, 2H), 7.92 (d, J = 5.4 Hz, 1H), 8.40- 8.44 (m, 1 H). m / z = 498.26 (M + H).

INTERMEDIARY 69 4- [2- (1-naphthyl) sulfonyl] thieno [3,2-c] pyridin-4-yl) -1,4-diazepane-1-tert-butyl carboxylate Procedure B from 4- [2 - (1-naphthyl) thio] thieno [3, 2-c] pyridin-4-yl) -1,4-diazepane-1-carboxylate (0.055 g, 0.112, mmoles) Oxone (0.27 g, 0.448 mmol); NaOAc (0.5 g) in EtOH (2 mL) followed by reverse phase chromatography (40-> 70) gave 15 mg of the product. Yield 26%, 93% pure. ½ NMR (270 MHz, CDC13) d 1.34 (s, 9H), 2.06-2.10 (m, 2H), 3.48-3.62 (m, 2H), 3.78-3.86 (m, 2H), 3.95-4.16 (m, 4H ), 7.19-7.31 (m, 2H>, 7.60-7.75 (m, 3H), 7.92-7.99 (m, 2H), 8.18 (m, J = .8.1 Hz, 1H), 8.50-8.53 (ra, 1H) ), 8.77-8.80 (m, 1H) m / z = 524.22 (M + H); EXAMPLE 84 4- (1, 4-Diazepan-1-yl) -2- [(3,4-dichlorophenyl) hydrochloride) sulfonyl] thieno [3,2-c] pyridine 4-. {2- 2- [(3,4-dichlorophenyl) sulfonyl] thieno [3,2- c] pyridin-4-yl.] - 1, 4 - tert-butyl diazepane-1-carboxylate from 3,4-dichlorothiophenol (60 mg, 15%), as a beige solid, by the application of General Procedures A and B described above: 1H NMR (CDC13) d 8.27 - 8.14 (m, 1H), 8.11-8.04 (m, 2H), 7.87-7.80 (m, 1H), 7.67-7.62 (m, 1H), 7.26-7.20 (m, 1H), 4.18-3.98 (m, 4) ?), 3.87-3.74 (m, 2H), 3.61-3.44 (m, 2H), 2.20-2.00 (m, 2H), 1.33 (s, 9H), MS m / z 542 (M + l). of the title (50 mg, 95%) was obtained as a beige solid, by the applied of General Procedure C described above. ¾ NMR (270 MHz, CH3OH-d4) d 8.48 (s, 1H), 8.30 (d, J = 1. 85 Hz, 1H), 8.05 (dd, J = 8.58, 1.98 Hz, 1H), 7.92 (d, J = 6. 86 Hz, 1H), 7.83 (d, J = 8.44 Hz, 1H), 7.69 (d, J = 6.86 Hz, 1H), 4.41-4.34 (m, 2H), 4.24-4.16 (m, 2H), 3.76- 3.69 (m, 2H), 3.51-3.43 (m, 2H), 2.52-2.42 (m, 2H); MS m / z 442 (M + 1). EXAMPLE 85 4- (1, 4-Diazepan-1-yl) -2- [1-naphthylsulfonyl) thieno [3, 2-c-pyridine] Hydrochloride The title compound was obtained from 4- [2- (1-naphthyl) sulfonyl-thieno - [3,2-c] pyridin-4-yl) -1,4-diazepane-1-tert-butyl carboxylate (15 mg, 0.029 mmol) following Method O to give 12 mg of the desired product, yield 90% , 95% pure. ¾ NMR (270 MHz, CH30H-d4) d 2.40-2.50 (m, 1H), 3.45- 3.55 (m, 2H), 3.65-3.75 (m, 2H), 4.06-4.26 (m, 2H), 4.27-4.46 (m, 2H), 7.58-7.80 (m, 4H), 7.83-7.86 (m, 1H), 8.06 (d, J = 8.1 Hz, 1H), 8.20 (d, J = 8.1 Hz, 1H), 8.48 ( s, 1H), 8.53-8.56 (m, 1H), 8.83-8.86 (ra, 1). m / z = 424.06 (M + H-HC1).

EXAMPLE 86 4- (1, 4-Diazepan-1-yl) -2- [4- tert-butylphenylsulfonyl) thieno [3,2-c] pyridine hydrochloride The title compound was obtained from 4- [2- (4 -tert-butylphenyl) -sulfonyl] thieno [3,2-c] pyridin-4-yl) -1,4-tert-butyl-4-diazepanedicarboxylate (6 mg, 11.3 mmol) following Method 0 to give 4 mg of the desired product, 76% yield, 88% pure. 1 H NMR (270 MHz, CH 3 OH-d 4) d 1.33 (s, 9 H), 2.41-2.47 (m, 2 H), 3.41-3.49 (m, 2 H), 3.65-3.78 (m, 2 H), 4.15-4.25 (m , 2H), 4.29-4.40 (m, 2H), 7.65-7.70 (m, 3H), 7.90 (d, J = 5.4 Hz, 1H), 8.00-8.04 (m, 2H), 8.37 (s, 1H). m / z = 430.06 (M + H-HC1). EXAMPLE 87 4- (1, 4-Diazepan-1-yl) -2- [3,4-dimethylphenylsulfonyl) thieno [3,2-c] pyridine hydrochloride The title compound was obtained from 4- [2- (3 , 4-dimethylphenyl) -sulfonyl] thieno [3,2-c] pyridin-4-yl) -1,4-diazepane-1-tert-butyl carboxylate (6 mg, 0.012 mmol) following Method O to give 6 mg of the desired product, 88% yield, 89% pure. ¾ NMR (270 MHz, C¾0H-d4) d 2.34 (s, 6H), 2.45-2.55 (m, 2H), 3.42-3.51 (m, 2H), 3.67-3.76 (m, 2H), 4.10-4.20 (m , 2H), 3.58-3.70 (m, 2H), 7.39-7. 1 (m, 1H), 7.64-7.67 (m, 1H), 7.79- 7.84 (m, 2H), 7.89-7.91 (m, 1H), 8.36 (s, 1H). m / z = 402.07 (M + H + HCl). EXAMPLE 88 2- [(4-Bromophenyl) sulfonyl] -4- (1-hydrochloride, 4- diazepan-1-yl) thieno [3,2-c] pyridine Trifluoroacetic acid (1 ml) was slowly added to a solution of 4-. { 2- [(4-bromophenyl) thio] thieno [3,2-cjpyridin-4-yl} - 1 / 4- tert-butyl diazepane-1-carboxylate (26 mg, 0.0-47 mmol) in CH2C12 at 0 ° C. The reaction mixture was allowed to reach room temperature, stirred for 40 minutes and then concentrated in vacuo. The residue was redissolved twice in MeOH and concentrated in vacuo. The residue was dissolved again in MeOH and an excess of 1 M HC1 in diethyl ether (4 mL) was slowly added to the solution. Removal of the solvents to the solvents afforded the title compound (21 mg, 91%) as a yellowish solid. 1H MR (270 MHz, DMSO-d6) d ppm 8.41 (s, 1H), 8.06-7.99 (m, 2H), 7.92 (d, J = 6.86 Hz, 1H), 7.87-7.80 (m, 2H), 7.66 (d, J = 6.86, 1H), 4.38 - 4.31 (m, 2H), 4.22 -4.14 (m, 2H), 3.74 - 3.67 (m, 2H), 3.50 - 3.42 (m, 2H), 2.51 - 2.39 ( m, 2H); MS m / z 452 (M + 1). EXAMPLE 89 2- (Phenylsul onyl) -4- piperazin-1-ylthieno [3,2-c] pyridine hydrochloride To a stirred solution of 4- [2- (phenylthio) thieno [3,2-cjpyridin-4-] ] piperazine-1-carboxylate (350 mg, 0.819 mol) in ethanol was added oxone in aqueous solution. The reaction was monitored by LCMS. When all the initial materials were consumed, the chroma ogram showed two main peaks, the product and the N-oxide. After purification by preparative HPLC, the resulting Boc material was treated with HC1 in ether. The solution was centrifuged and the supernatant was removed. Ether was added, then centrifuged and decanted (three times) to remove excess HC1. The remaining ether was finally evaporated in a SpeedVac concentrator. Yield 18%, purity by HPLC = 98%, m / z = 360.0 (M + H). ¾ NMR (270 MHz, CH 3 OH-d 4) d ppm 3.56 (m, 4 H) 4.08 (m, 4 H) 7.68 (m, 4 H) 7.77 (dd, J = 6.60, 0.79 Hz, 1 H) 8.04 (d , J = 6.33 Hz, 1 H) 8.12 (m, 2 H) 8.39 (d, J = 0.79 Hz, 1 H). EXAMPLE 90 2- (3-Methoxy-benzenesulfonyl) -4-piperazin-1-ylthieno [3,2-c] pyridine hydrochloride The 4- [2- (3-methoxy-phenylsulfanyl) tert-butyl ester] - thieno [3,2-c] pyridin-4-yl] -piperazine-1-carboxylic acid, was obtained from 3-methoxythiophenol (130 μ ?, 1 mmol) and 4- (2-bromothieno [3, 2-c] pyridin-4-yl) piperazin-1-tert-butyl carboxylate (215 mg, 0.52 mmol). 120 mg, 50%) was obtained by means of the application of General Method M described above. aH NMR (270 MHz, CDC13) d 1.48 (s, 9 H), 3.42-3.51 (m, 4 H), 3.58-3.67 (m, 4 H), 3.74 (s, 3 H), 6.76 (dd, J = 8.18, 2.3 8 Hz, 1H), 6.84-6.92 (m, 2 H), 7.16-7.23 (m, 2 H), 7.51 (s, 1 H), 8.04 (d, J = 5.81 Hz, 1 H); MS m / z 458 (M + 1). Accordingly, the title compound was obtained from 4- [2- (3-methoxy-phenylsulfa-yl) -thieno [3, 2-c] pyridin-4-yl] -piperazine-1-carboxylic acid tert-butyl acid ( 7 mg, 7%), after trituration with diethyl ether, as a beige solid, by application of General Methods B and C described above. LH NMR (270 MHz, CD3OD) d 8.31 (s, 1H), 8.09 (d, J = 6.33 Hz, 1H), 7.71-7.62 (m, 2H), 7.59-7.50 (m, 2H), 7.30-7.23 ( m, 1H), 3.98-3.92 (m, 4H), 3.87 (s, 3H), 3.54-3.48 (m, 4H); MS m / z 390 (M + 1). EXAMPLE 91 2- (4-Methoxy-benzenesulfonyl) -4-piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride The tert-butyl ester of 1-carboxylic acid was obtained from 4-methoxythiophenol (130μ ,, 1 mmol) and 4- (2-bromothieno [3,2- c] pyridin-4-yl) piperazine-1-carboxylic acid tert-butyl ester (215 mg, 0.52 mmol). 100 mg, 42% were isolated by the application of General Method M, described above. ¾ MR (270 MHz, CDC13) d 1.48 (s, 9 H), 3.40 - 3.47 (m, 4H), 3.58-3.65 (m, 4H), 3.79 (s, 3H), 6.83- 6.89 (m, 2H) , 7.15 (d, J = 5.54 Hz, 1H), 7.35 (s, 1H), 7.38-7.43 (m, 2H), 7.99 (d, J = 5.81 Hz, 1H); MS m / z 458 (M + 1). The 4- [2- (4-methoxyphenylsulphanyl) thieno [3,2-c] pyridin-4-yl] -piperazine-1-carboxylic acid tert -butyl ester (25 mg, 23%) was obtained as a clear liquid by the application of General Procedure B described above. XE NMR (270 MHz, CDCl 3) d 1.48 (s, 9 H), 3.40-3.47 (m, 4 H), 3.58- 3.65 (m, 4 H), 3.79 (s, 3 H), 6.83-6.89 (m , 2 H), 7.15 (d, J = 5.54 Hz, 1 H), 7.35 (s, 1 H), 7.38-7.43 (m, 2 H), 7.99 (d, J = 5.81 Hz, 1 H); MS m / z 458 (M + 1). The title compound was obtained following the Procedure C): ¾ NMR (CD30D) d 8.25 (s, 1H), 8.09-7.89 (m, 3H), 7.69 (d, J = 6.33 Hz, 1H), 7.17-7.10 (m, 2H), 4.00-3.93 (m, 4H), 3.87 (s, 3H), 3.55-3.48 (m, 4H); MS LMLS 390 (M + l). EXAMPLE 92 4- Piperazin-1-yl-2- Hydrochloride. { [4-trifluoromethyl) phenyl] sulfonyl} thieno [3,2-c] pyridine 2- was dissolved. { [4- (trifluoromethyl) phenyl] thio} 4-piperazin-1-ylthieno [3,2-c] pyridine (0.42 mmol) in TFA (1.5 ml) at 0 ° C, stirred for 15 minutes and H202 was added. The mixture was stirred at room temperature overnight. NaOH (2M) was added, extraction with ethyl acetate (3x), washed with brine, dried over NaSO4. The solvent was removed and the product was purified by preparative HPLC to give 154.7 mg (86.2%). 1H NMR (270 MHz, DMS0-d6) d ppm 9.79 (s, 1H) 8.56 (s, 1 H) 8.35 (d, J = 8.44 Hz, 2 H) 8.12-8.05 (? A, 3H) 7.79 (d, J = 6.33 Hz, 1 H) 3.98-3.96 (m, 4H) 3.32-3.31 (m, 4H); LC-MS 428 (M-H) Purity (HPLC) 95%. EXAMPLE 93 2- [(2-tert-Butylphenyl) sulfonyl] -4-piperazin-1-ylthieno [3,2-c] pyridine hydrochloride The title compound was prepared following the Method M-O. yield: 10.6 mg (6.3%) of 2- [(2-tert-butylphenyl) sulfonyl] -4- piperazin-1-ylthieno [3,2-c] pyridine hydrochloride. ¾ NMR (270 MHz, DMS0-d6) d ppm 9.57 (s, 1 H) 8.42 (s, 1 H) 8.26-8.22 (m, 1H) 8.06-8.04 (m, 1H) 7.68-7.55 (m, 4H) 3.87-3.86 (m, 4H) 3.34-3.33 (m, 4H) 1.51-1.43 (m, 9H); LC-MS 400 (M-H) +; Purity (HPLC) 90%. EXAMPLE 94 2- [(3, 4-Dichlorophenyl) sulfonyl] -4-piperazin-1-ylthieno [3,2-c] pyridin-2-sulfonamide hydrochloride The title compound was prepared following the Method M-0. Yield: 47.9 mg (22.9%). ¾ NMR (270 MHz, DMS0-ds) dm 9.36 (s, 1 H) 8.51 (s, 1 H) 8.38 (d, J = 2.11 Hz, 1 H 8.06-7.94 (m, 3H) 7.70-7.68 (m , 1H) 3.81-3.77 (m, 4H) 3.31-3.29 (m, 4H); LC-MS 427 (M-1H); Purity (HPLC) 95% EXAMPLE 95 2- [(4-tert-Butylphenyl) Hydrochloride ) sulfonyl] -4-piperazin-1-ylthieno [3,2-c] pyridine Oxone (0.52 g, 0.84 min) was added in water (4 ml), adjusted to pH ~ 6 with sodium oxide acetate, at 2 ° C. - [(4-tert-Butylphenyl) thio] -4- piperazin-1-ylthieno [3,2-c] pyridine (0.42 mmol) in ethanol (30 mL) The mixture was stirred at room temperature for 2 hours and was stirred at room temperature for 2 hours. added more oxone (0.52 g, 0.84 mmol) The reaction was stirred overnight, water was added to the mixture, extracted with dichloromethane (2 x 20 mL) and the solvent was removed.The products were purified by preparative HPLC. Yield: 41.9 mg (22.0%.). ¾ NMR (500 MHz, CH3OH-d4) d ppm 8.38 (s, 1 H) 8.05-8.01 (m, 3H) 7.80 (d, J = 6.59 Hz, 1 H) 7.71-7.69 (m, 2H) 4.15-4.13 (m, 4H) 3.59-3.57 (4H) 1.37-1.33 (M, 9 H); LC-MS 416 (M-H) +; Purity (HPLC) 95%. 1 EXAMPLE 96 2- (1-Naphthylsulfonyl) -4- piperazin-1-ylthieno [3,2-c] pyridine hydrochloride The title compound was prepared following the method -O. Yield: 3.4 mg (0.2%). ?? NMR (270 MHz, DMS0-d6) d ppm 9.34 (s, 1 H) 8.82 (s, 1 H) 8.44 (s, 1 H) 8.26-8.06 (m, 5H) 7.79-7.65 (m, 3H) 3.79- 3.78 (m, 4H) 3.32-3.30 (m, 4H); LC-MS 410 (M-H) +; Purity (HPLC) 95%. EXAMPLE 97 2- [(3-Fluorophenyl) sulfonyl] -4-piperazin-1-ylthieno [3,2-c] pyridin-2-sulfonamide hydrochloride 2-bromo-4-chlorothieno [3, 2-c] pyridine (190 mg, 0.50 mmol) in DMF (1 mL) to 3-fluorobenthiol (95.5 mg, 1.0 mmol.), OH (56 mg, 0.2 mmol) and CU2O (71 mg, 0.5 mmol = in DMF (1 mL). The reaction was heated to 120 ° C overnight The mixture was filtered through a plug of silica and the solvent was removed The product was dissolved in TFA (1.5 ml) at 0 ° C and the solution was stirred for 15 minutes, H202 (100 μl) was added and the mixture was stirred at room temperature overnight, 2M NaOH was added, it was extracted with ethyl acetate, washed with brine and the solvent was removed. by preparative HPLC Yield: 30.1 mg (16.1%) XH NMR (270 MHz, DMSO-d6) d ppm 9.34 (s, 1 H) 8.45 (s, 1 H) 8.16 (d, J = 5.69 Hz, 1 H ) 7.97-7.93 (m, 2H) 7.76-7.62 (m, 3H) 3.30 (s, 4 H) (4H obscured by the solvent signal); LC-MS 378 (M - H); HPLC Purity) 99%.

EXAMPLE 98 2- (Mesitylsulfonyl) -4- piperazin-1-ylthieno [3,2-c] pyridine hydrochloride The title compound was prepared following Method M-0. Yield: 32.0 mg (16.1%). NMR LE (270 MHz, DMSO-d6) d ppm 9.32 (s, 1 H) 8.20- 8.14 (m, 2H) 7.66 (d, J = 5.69 Hz, 1 H) 7.14 (s, 2 H) 3.29 (s, 4 H) 2.65 (s, 6H) 2.28 (s, 3H) (4H darkened by the solvent signal); LC-MS 402 (M-H) +, Purity (HPLC) 95% EXAMPLE 99 2- [(2-Methoxyphenyl) sulfonyl] -4-piperazin-1-ylthieno [3,2-c] pyridine hydrochloride The compound The titre was prepared following the M-0 Method: yield: 14.7 mg (7.6%) lR NMR (270 MHz, DMS0-d6) d ppm 9.33 (s, 1 H) 8.24 (s, 1 H) 8.15 (d, J = 5.94 Hz, 1 H) 8.00 (dd, J = 7.92, 1.48 Hz, 1 H) 7.77-7.68 (m, 2H) 7.28-7.18 (m, 2H) 3.30 (s, 4H) (7H obscured by the signal of the solvent); LC-MS 390 (M-H) + (HPLC) 99% EXAMPLE 100 2- [(2,4-Dimethoxyphenyl) sulfonyl] -4-piperazin-1-ylthieno [3,2-c] hydrochloride ] pyridine The title compound was prepared following Method M-0 Yield: 42.7 mg (20.5%). 1 H NMR (270 MHz, DMSO-d 6) d ppm 9.39 (s, 1 H) 8.37 (s, 1 H) 8.13 (d, J = 5.69 Hz, 1 H) 7.68-7.66 (m, 2H) 7.54 (d, J = 2.23 Hz, 1 H) 7.19 (d, J = 8.66 Hz, 1 H) 3.29 (s, 4 H) (10 H obscured by the solvent signal); LC-MS 420 (M -H) +; HPLC Purity) 98%. EXAMPLE 101 2- [(2,4-Dimethylphenyl) sulfonyl] -4-piperazin-1-ylthieno [3,2-a] pyridine hydrochloride The title compound was prepared following Method M-0. Yield: 17.8 mg (9.3%). ¾ NMR (270 MHz, DMSO-d6) d ppm 9.32 (s, 1H) 8.27 (s, 1 H) 8.15 (d, J = 5.94 Hz, 1 H) 8.00 (d, J = 8.17 Hz, 1 H) 7.67 (d, J = 5.94 Hz, 1 H) 7.35-7.26 (m, 2H) 3.29 (s, 4H) 2.34 (5, 5 3H) (7H obscured by the solvent signal); LC-MS 388 (M-H) + Purity (HPLC) 98%. EXAMPLE 102 2- [(2,5-Dimethylphenyl) sulfonyl] -4-piperazin-1-ylthieno [3,2-c] pyridine hydrochloride The title compound was prepared following the Method M-O. Yield: 16.9 mg (8.8%). ½ NMR (270 MHz, DMSO-d5) d ppm 9.17 (s, 1 H) 8.29 (s, 1 H) 8.18-18.15 (m, 1H) 7.94 (s, 1 H) 7.66 (d, J = 5.69 Hz, 1 H) 7.47 (d, J = 7.67 Hz, 1 H) 7.32 (d, J = 8. 1 6 Hz, 1 H) 3.29 (s, 2 H) 2.42 (s, 3 H) (7H obscured by the signal of the solvent); LC-MS 388 (M-H) +; HPLC Purity) 99%.

EXAMPLE 103 2- [(2-Ethylphenyl) sulfonyl] -4-piperazin-1-ylthieno [3,2-c] pyridine hydrochloride The title compound was prepared following Method M-O. Yield: 22.6 mg (11.2%). ¾ NMR (270 MHz, DMS0-d6) d ppm 9.19 (s, 1H) 8.32 (s, lH) 8.17 (d, J = 5.69, 1H) 8.08 (d, J = 7.92 Hz, 1 H) 7.73- 7.66 (m, 2H) 7.52 (t, J = 7.67 Hz, 2 H) 3.29. (S, 4 H) 3.00 (q, J = 7.34 Hz, 2 H) 1 -10 (m, 3 H) (4H obscured by solvent signal LC-MS 388 (M-H) +; Purity (HPLC) 100% Reaction Scheme 7 Legend of Reaction Scheme 7: i) nBuLi, diethyl ether; ii) S02 gas; iii) benzyl bromide (s), DMF, heat; iv) diamine (s), K2C03, DMF, heat; v) HC1, diethyl ether. INTERMEDIARY 70 4- Lithium chlorothieno [3,2-c] pyridin-2-sulfinate 2-bromo-4-chlorothieno [3, 2-c pyridine (5.00 g, 20.1 mmol) in dry ether (100 ml) was suspended and the mixture was cooled to -78 ° C under N2 atmosphere, n-BuLi (1.6 M in hexane, 15 ml) was added and the reaction mixture was stirred at -78 ° C for 2 hours. After the bubbling had stopped, the reaction mixture was stirred for a further hour at -78 ° C and then allowed to warm to room temperature. with ether to give the lithium sulfonate salt (3.59 g, 74%) which was used in the next step without further purification ¾ NMR (270 MHz, DMS0-d6) d ppm 7.26 (s, 1H) 7.99 (d, J = 5.54 Hz, 1H) 8.14 (d, J = 5.54 Hz, 1H). MS (M-Li + 1) 234. Benzylation of sulfinate salts (Method P) To a suspension of lithium 4-chlorothieno [3,2-c] pyridin-2-sulfate (100 mg, 0.42 mmol) in dry DMF (2 ml) was added benzyl bromide (0.83 mmol, 2 equiv.) And the mixture was heated with stirring for 16 hours at 110 ° C. Analysis by LCMS showed the desired product and no initial material remaining. The mixture was treated with diethyrene thiophenol (200 mg) and rotated for 16 hours. The suspension was washed by filtration with additional DMF (2 ml). This material was further reacted without purification. Nucleophilic Substitution of Chlorine (Method Q) To potassium carbonate (172 mg) was added to crude solutions of benzylsulfone in DMF (4 mL)., 1.25 mmol) and tert-butyl piperazin-1-carboxylate (155 mg, 0.84 mmol). The resulting mixtures were heated for 16 hours at 110 ° C. The LCMS showed the desired compound and no material started. The reaction mixtures were filtered and then the solvent was removed under reduced pressure. The desired compounds were isolated pure following preparative HPLC. BOC deprotection (Method R) N-protected piperazine derivatives with BOC were dissolved in HCl / diethyl ether (1 mL, 1.0 M) at room temperature and stirred for 16 hours. Removal of the solvent under reduced pressure gave the crude hydrochloride salts. Titration with acetonitrile gave the desired compound as a white solid. INTERMEDIARY 71 4- [2- (benzylsulfyl) thieno [3,2-c] pyridin-4-yl] piperazin-1-tert-butyl carboxylate 4-chlorothieno [3,2- c] pyridin- 2- was treated lithium sulfate (0.44 moles) with benzyl bromide (0.59 mmoles) as described in Method P above and then further reacted with piperazine-1-tert-butyl carboxylate as described in Method Q. yield 0.009 g (7% during two stages ¾ NMR (300 MHz, CDC13) d 8.14 (d, J = 5.5 Hz, 1H), 7.27 - 7.40 (m, 5H), 7.15 - 7.21 (m, 2 H) 4.45 (s) , 2 H), 3.50-3.56 (m, 4 H), 3.40-3.45 (m, 4 H), 1.49 (s, 9 H); MS (ESI +) for C 23 H 27 N 3 O 4 S 2 m / z 474 (M + H) +. HPLC 77%, RT 3.93 min (ACE3 CS Dx4 mm, 5-50% acetonitrile in 3 min). INTERMEDIARY 72 4- (2- { [4- (trifluoromethyl) benzyl] sulfonyl} thieno [3,2-c] pyridin-4-yl) piperazin-1-tert-butyl carboxylate 4-chlorothieno [3,2-c] pyridin-2-sulfinate lithium was treated with 4- (trifluoromethyl) benzylbromide (0.59 mmoles) as described in Method P above and then further reacted with tert-butyl piperazin-1-carboxylate as described in Method QF. Product 0.02 g (16% in the two stages). Solid beige. 4? MR (300 MHz, CDCI3) d 8.16 (d, J = 6 Hz 1 H), 7.53- 7.61 (d, J = 9 Hz 2 H), 7.49 (s, 1 H), 7.26-7.36 (m, 4 H) ), 4.51 (s, 2 H), 3.49-3.60 (m, 4 H), 3.36-3.49 (m, 4 H),? .49 (s, 9 H); MS (ESI +) for C 24 H 26 F 3 N 3 O 4 S 2 m / z 542 (M + H) +. HPLC 71%, RT = 4.07 min (ACE3 C8 50x4 mrn, 5-50% acetonitrile in 3 min). INTERMEDIARY 73 4-. { 2- [(3-bromobenzyl) sulfonyl] thieno [3,2-c] pyridin-4-yl} piperazin-1-tert-butyl carboxylate

[0000] 4-Chloro-thieno [3,2-c] pyridin-2-sulfinate lithium (0.44 mmol) was treated with 3-bromobenzyl bromide (0.59 mmol) as described in Method P above and then reacted with tert-butyl piperazin-1-carboxylate as described in Method Q. Product 0.023 g (10% in the two steps). Solid beige. ¾ NMR (300 MHz, CDC13) d 8.16 (d, J = 6 Hz, 1H), 7.50-7.55 (a, 2 H), 7.32-7.40 (m, 2 H), 7.10-7.24 (m, 3 H) , 4.44 (s, 2 H), 3.61-3.73 (m, 8 H), 1.50 (s, 9 H); MS (ESI +) for C23H26BrN304S2 m / z 554 (M + H) +. HPLC 77%, RT = 1.07 min (ACE3 C8 50x4.6 mm, 5-50% acetonitrile in 3 min). INTERMEDIARY 74 4- (2- { [3- (trifluoromethyl) benzyl] sulf "onyl.} Thieno [3,2-c] pyridin-4-yl) piperazin-1-tert-butyl carboxylate It was treated 4-lithium [3, 2-c] pyridin-2-sulfinate (0.44 mmol) with 3-bromobenzyl bromide (0.59 mmol) as described in Method P above and then reacted with piperazine-1-carboxylate of tert-butyl as described in Method Q. Product 0.023 g (10% in the two stages) Beige solid XH NMR (300 MHz, CDC13) d 8.14 (d, J = 6 Hz, 1 H), 7.85 -7.91 (m, 1 H), 7.61-7.72 (m, 2 H), 7.50-7.60 (m, 1 H), 7.12-7.31 (m, 2 H), 4.74 (s, 2 H), 3.52-3.71 (m, 8 H), 1.50 (s, 9 H), MS (ESI +) for C24H26F3 3O4S2 m / z 542 (M + H) +, HPLC 85%, RT = 2.13 min (YMC ODS AQ, 33x3 mm, 10 -90% acetonitrile in 3 min.) INTERMEDIARY 75 4- (2- { [2,5- bis (trifluoromethyl) benzyl] sulfonyl} thieno [3,2-c] pyridin-4-yl) piperazine 1-tert-butyl carboxylate 4-chlorothieno [3,2-c] pyridin-2-sulfinate was treated io (0.44 mmol) with 2,5-bis (trifluoromethyl) benzyl bromide (0.59 mmol) as described in Method P above and then reacted with tert-butyl piperazin-1-carboxylate as described in the Method Q. Product 0.01 g (4% in the two stages). Solid beige. ½ MR (300 MHz, CDCl3) d 8.16 (d, J = 5.8 Hz 1H), 8.00 (s, 1 H), 7.74-7.85 (m, 3 H), 4.76 [s, 2 H), 3.56-3.64 ( m, 4 H), 3.47-3.56 (m, 4 H), 1.49 (s, 9 H); MS (ESI +) for C25H25F6 3O S2 m / z 610 (M + H) +. HPLC 73%, RT = 2.36 min (YMC ODS AQ, 33x3 mm, 10-90% acetonitrile in 3 min). INTERMEDIARY 76 4-. { 2- [(4-methylbenzyl) sulfonyl] thieno [3,2-c] pyridin-4-yl} piperazin-1-tert-butyl carboxylate It was treated as 4-chlorothieno [3,2-c] pyridin-2-sulfinate lithium (0.44 mmol) with 4-methylbenzyl bromide (0.59 mmol) as described in Method P above and then further reacted with tert-butyl piperazin-1-carboxylate as described in Method Q. Product, 0.005 g (3% in the two steps). Solid beige.

XH NMR (300 MHz, CDC13) d 8.15 (d, J = 6 Hz 1 H), 7.40 (s, 1 H), 7.00-7.16 (m, 4 H), 4.42 (s, 2 H), 3.46-3.60 (m, 4 H), 3.37-3.46 (m, 4 H), 2.34 (s, 3 H), 1.49 (s, 9 H); MS (ESI +) for C 24 H 29 N 3 O 4 S 2 m / z 488 (M + M) +. HPLC 69%, RT = 2.06 min (YMC ODS AQ, 33x3 mm, 10-90% acetonitrile in 3 min). INTERMEDIARY 77 4- (2- { [5- Chloro-2- (trifluorornethyl) benzyl] sulfonyl} thieno [3,2-c] pyridin-4-yl) piperazine-1-carboxylic acid tert-butyl ester treated with 4-chlorothieno [3,2-c] pyridin-2-sulfinate lithium (0.44 mmol) with 5-chloro-2- (trifluoromethyl) benzyl bromide (0.59 mmol) as described in Method P above and then further reacted with tert-butyl piperazin-1-carboxylate as described in Method Q. Product 0.019 g (7.5% in the two stages). Solid beige. ½ NMR (300 MHz, CDC13) d 8.12-8.14 (m, 1 H), 7.80-7.88 (m, 2 H), 7.47-7.66 (m, 2 H), 4.71 (s, 2 H), 3.74-3.83 (m, 4 H), 3.63-3.72 (m, 4 H), 1.49 (s, 9 H); MS (ESI +) for C 24 H 25 ClF 3 N 3 O 4 S 2 m / z 576 (M + H) + HPLC 74%, RT 2.30 min (YMC ODS AQ, 33x3 mm, 10-90% acetonitrile in 3 min). INTERMEDIARY 78 4-. { 2- [(3, 4-difluorobenzyl) sulfonyl] thieno [3,2-c] pyridin-4-yl} 3-tert-butyl piperazin-1-carboxylate 4-chlorothieno [3,2-c] pyridin-2-sulfinate lithium (0.44 mmol) was treated with 3,4-bis (trifluoromethyl) benzyl bromide (0.59 mmol) as described in Method P above and then further reacted with tert-butyl piperazin-1-carboxylate as described in Method Q. Product 0.014 g (6% in the two steps). Solid beige. E NMR (300 MHz, CDC13) d 8.17-8.21 (m, 1 H, 7.71 (s, 1 H), 7.07 - 7.39 (m, 4 H), 4.59 (s, 2 H), 3.55 - 3.68 (m, 8 H), 1.49 (s, 9H) MS (ESI +) for C23H25F2N3O4S2 m / z 510 (M + H) +, 64% HPLC, RT = 2.02 min (YMC ODS AQ, 33 x 3 mm, 10-90% acetonitrile in 3 minutes. 79 4- {2- [(3, 5-dimethoxybenzyl) sulfonyl] thieno [3f2-c] pyridin-4-yl) piperazin-1-tert-butyl carboxylate 4-chlorothieno [3, 2-c] ] lithium pyridine-2-sulfinate (0.44 mmol) with 3,5-dimethoxybenzyl bromide (0.59 mmol) as described in Method P above and then further reacted with tert-butyl piperazine-1-carboxylate as described described in Method Q. Product 0.02 g (10% in the two stages) Solid beige.

XH NMR (300 MHz, CDC13) d 8.17-8.21 (m, 1 H), 7.71 (s, 1 H), 7.07-7.39 (m, 4 H), 4.59 (s, 2 H), 3.55-3.68 (m , 8 H), 1.49 (s, 9 H); MS (ESI +) for C 23 H 25 F 2 N 3 O 4 S 2 m / z 510 (M + H) +. HPLC 64%, RT = 2.02 min (Y C ODS AQ, 33x3 min, 10-90% acetonitrile in 3 min). EXAMPLE 104 4- (Piperazinyl-2- (3-methoxybenzylsulfonyl) -thienopyridine) A 1: 1 mixture of lithium 4-chlorothienopyridine-2-sulfinate (0.176 g, 0.734 mol) was heated at 100 ° C for 2 hours. ) and 2-methoxybenzyl bromide (0.295 g, 1.47 mmol) in DMF (5 ml). To the mixture was added Boc-piperazine (546 mg, 2.94 mmol) and the reaction was heated at 110 ° C for 1.5 hours. The solvent was removed and the crude product was purified by preparative HPLC to obtain 17.4 mg of 4- (4-t-butyloxycarbonyl-piperazinyl) -2- (3-methoxybenzylsulfonyl) -thieno pyridine. Boc was dissolved in 2 mL of MeOH and 4 mL of HCl / ether was added to obtain 21.9 mg of 4- (piperazinyl) -2- (3-methoxybenzylsulfonyl) -thienopyridine. ¾ NMR (CD3OD / D20 1: 1) d 6.42-6.38 (m, 1H), 7.51-7.4S (m, 1 H), 7.39-7.35 (m, 1H), 6.92-6.85 (m, 1H), 6.64-6.59 (m, 1H), 6.48- 6.39 (m, 2H), 3.64-3.58 (m, 4H), 3.19-3.13 (m, 4H), 2.96 (s, 3H), 2.92 (s, 2H), MS (ESI) 404 (M + H ) +; Pure za (HPLC, column YMC) 94%. INTERMEDIARY 80 4- [2- (Benzylsulfonyl) thieno [3,2-C] pyridin-4-yl] piperazin-1-tert-butyl carboxylate 4-chlorothieno [3,2- c] pyridin-2-sulfinate was treated of lithium (0.44 mol) with benzyl bromide (0.59 mmol) as described in Method P above and then further reacted with piperazin-1-tert-butyl carboxylate as described in Method Q. Product 0.00 g ( 7%) in the two stages). Solid beige. ?? NMR (300 MHz, CDC13) d 8.14 (d, J = 5.5 Hz 1 H), 7.27-7.40 (m, 5 H), 7.15-7.21 (m, 2 H), 4.45 (s, 2 H), 3.50- 3.56 (m, 4 H), 3.40-3.45 (m, 4 H), 1.49 (s, 9 H); MS (ESI +) for C 23 H 27 N 3 O 4 S 2 m / z 474 (M + H) +. HPLC 77%, RT = 3.93 min (ACE3 C8 50x4 mm, 5-50% acetonitrile in 3 min). EXAMPLE 105 2- (Benzylsulfyl) -4- piperazin-1-ylthieno [3,2-c] pyridine hydrochloride. 4- [2- (Benzylsulfonyl) thieno [3,2- c] pyridin-4-yl] was treated. piperazin-1-tert-butyl carboxylate (0.01 g, 0.02 mmol) as described in Method R to give the desired product as a white solid. Product, 0.009 g, (100%). White solid. ¾ NMR (300 MHz, DMSO-d6) d 8.98 (s, 1 H), 8.13-8.20 (d, J = 8 Hz, 1 H), 8.00 (s, 1 H), 7.64-7.71 (m, 1 H) , 7.18-7.35 (m, 5 H), 4.93 (s, 2 H), 3.63 (m, 4H), 3.22-3.34 (m, 4H); MS (ESI +) for CisHigNsOaSz. C1H m / z 374 (M + H) +. HPLC 90%, RT = 2.91 min (ACE3 C8 50 x 4.6 mm, 5-50% acetonitrile in 3 min). INTERMEDIARY 81 4- (2- { [4- (trifluoromethyl) benzyl] sulfonyl} thieno [3,2-c] pyridin-4-yl) piperazin-1-tert-butyl carboxylate 4- Chlorotiene was treated [3, 2-c] pyridin-2-sulfinate lithium (0.44 mol) with 4- (trifluoromethyl) benzyl bromide (0.59 mmol) as described in Method P above and then further reacted with piperazin- 1- tert-butyl carboxylate as described in Method Q. Product, 0.02 g (16% in the 2 steps). Solid beige. ¾ NMR (300 MHz, CDC13) d 8.16 (d, J = 6 Hz, 1 H), 7.53-7.61 (d, J = 9 Hz 2 H), 7.49 (s, 1 H), 7.26-7.36 (m, 4 H), 4.51 (s, 2 H), 3.49-3.60 (m, 4 H), 3.36-3.49 (m, 4 H), 1.49 (s, 9 H); MS (ESI +) for C 24 H 26 F 3 N 3 O 4 S 2 m / z 542 (M + H) +. HPLC 71%, RT = 4.07 min (ACE3 C8 50x4 mm, 5-50% acetonitrile in 3 min). EXAMPLE 106 4- Piperazin-1-yl-2- Hydrochloride. { [4- (trifluoromethyl) benzyl] sulfonyl} ieno [3, 2-c] pyridine. 4- (2- { [4- (trifluoromethyl) -benzyl] sulfonyl} thieno [3,2- c] pyridin-4-yl) piperazin- 1- was treated. tert-butyl carboxylate (0.02 g, 0.03 mmol) as described in Method R to give the desired product as a white solid. Product 0.014 g (100%) White solid.

LH NMR (300 MHz, DMSO-d6) d 9.25 (s, 1 H), 8.12-8.22 (m, 2 H), 7.66-7.77 (m, 4 H), 7.41-7.52 (m, 2 H), 5.12 (s, 2 H), 3.22-3.35 (m, 4 H); MS (ESI +) for Ci9H18F3N302S2. C1H m / z 442 (M + H) +. HPLC 90%, RT = 3.53 min (ACE3 C8 50x4.6 mm, 5-50% acetonitrile in 3 min). INTERMEDIARY 82 4-. { 2- [(3-bromobenzyl) sulfonyl] thieno [3,2-c] pyridin-4-yl} piperazin-1-tert-butyl carboxylate.

Lithium 4-chlorothieno [3,2-c] pyridin-2-sulfinate (0.44 mol) was treated with 3-bromobenzyl bromide (0.59 mmol) as described in Method P above and then further reacted with piperazine. 1-tert-Butyl carboxylate as described in Method Q. Product 0.023 g (10% in the two stages). Solid beige. aH NMR (300 MHz, CDC13) d 8.16 (d, J = 6 Hz, 1H), 7.50-7.55 (m, 2 H), 7.32-7.40 (m, 2 H), 7.10-7.24 (m, 3 H) , 4.44 (s, 2 H), 3.61-3.73 (m, 8 H), 1.50 (s, 9 H); MS (ESI +) for CasHaeBr aC Sz m / z 554 (M + H) + HPLC 77%, RT = 4.07 min (ACE3 C8 50x4.6 mm, 5-50% acetonitrile in 3 min). EXAMPLE 107 2- [(3-Bromobenzyl) sulfonyl] -4-piperazin-1-ylthieno [3,2-c] pyridine hydrochloride. { 2- [(3-bromobenzyl) sulfonyl] thieno [3,2-c] pyridin-4-yl} piperazin-1-tert-butyl carboxylate (0.023 g, 0.04 min) as described in Method R to give the desired product as a white solid. Product 0.013 g (67%) White solid. 1 H NMR (300 MHz, DMSO-d 6) d 9.19 (s, 1 H), 8.18 (d, J = 6 Hz, 1 H), 8.05 (s, 1 H), 7.70 (d, J = 6 Hz, 1 H), 7.53-7.5 8 (m, 1 H), 7.43-7.45 (m, 1 H), 7.19-7.32 (m, 2 H), 4.98 (s, 2 H), 3.24-3.35 (m7 4 H); MS (ESI +) for 3.30 min (ACE3 C8 50x .6 mm, 5-50% acetonitrile in 3 min). INTERMEDIARY 83 4-. { 2- [(3, 4-difluorobenzyl) sulfonyl] thieno [3,2-c] pyridin-4-yl} tert-butyl piperazin-1-carboxylate 4-chlorothieno [3, 2-c] pyridin-2-sulfinate lithium (0.44 mol) was treated with 3,4-bis (trifluoromethyl) benzyl bromide (0.59 mol) as described in Method P above and then further reacted with tert-butyl piperazin-1-carboxylate as described in Method Q. Product 0.014 g (6% in the two steps). Solid beige. ½ NMR (300 MHz CDC13) d 8.17-8.21 (m, 1 H), 7.71 (s, 1 H), 7.07-7.39 (m, 4 H), 4.59 (s, 2 H), 3.55-3.68 (m, 8 H), 1.49 (s, 9 H); MS (ESI +) for C 23 H 25 F 2 N 3 O 4 S 2 m / z 510 (M + H) +. HPLC 64%, RT = 2.02 min (YMC ODS AQ, 33x3 mm, 10-90% acetonitrile in 3 min). EXAMPLE 108 2- [(2, 3-difluorobenzyl) sulfonyl] -4- piperazin-1-ylthieno [3,2-c] pyridine hydrochloride The BOC group was removed from 4. { 2- [(3,4-difuorobenzyl) sulfonyl] thieno [3,2-c] pyridin-4-yl} piperazin-1-tert-butyl carboxylate using the Method R. Product, 0.068 g (100%). White solid. ½ NMR (300 MHZ, DMSO-d6) d 9.34 (s, 1 H), 8.22 (s, 1 H), 8.18 (d, J = 5.5 Hz, 1 H), 7.70 (d, J = 5.5 Hz, 1 H), 7.26-7.35 (m, 1 H), 7.15- 7.22 (m, 1 H), 7.05 -7.14 (m7 1 H), 5.08 (s, 2 M, 3.34-3.42 (m, 4 H), 3.25-3.34 (m, 4 H) MS (ESI +) for CISHITFSOZSZ-CIH m / z 410 (M + H ) +. HPLC 90%, RT = 1.07 min (YMC ODS AQr 33 x 3 mm, 20-50% acetonitrile in 1.5 min) EXAMPLE 109 2- [(4-Bromobenzyl) sulfonyl] -4-piperazin-1- hydrochloride iltieno [3,2-c] pyridine 4-chlorothieno [3,2-c] pyridin-2-sulfinate lithium (0.42 mmol) was treated with 4-bromobenzyl bromide (0.59 mmol) as described in Method P above and then further reacted with tert-butyl piperazine-1-carboxylate as described in Method Q. The BOC protecting group was removed using Method R.

Product 0.024 g (12% in the three stages). White solid.

½ NR (300 MHz, CDC13) d 8.16 (d, J = 5.8 Hz, 1 H), 8.00 (s, 1 H), 7.74-7.85 (m, 3 H), 4.76 (s, 2 H), 3.56- 3.64 (m, 4 H), 3.47- 3.56 (m, 4H), 1.49 (s, 9H); MS (ESI +) for C25H25F6N3O S2 m / z 610 (M + H) +. HPLC 73%, RT = 2.36 min (YMC ODS AQ, 33x3 mm, 10-90% acetonitrile in 3 min). INTERMEDIARY 84 4- (2- {[2,5- bis (tri-loromethyl) benzyl] sulfonyl} thieno [3,2-c] pyridin-4-yl) piperazin-1-tert-butyl carboxylate treated with 4-chlorothieno [3,2-c] pyridin-2-sulfinate lithium (0.44 mmol) with 2,5-bis (trifluoromethyl) benzyl bromide (0.59 mmol) as described in Method P above and then further react with tert-butyl piperazin-1-carboxylate as described in Method Q. Product 0.01 g (4% in the two steps). Solid beige. ¾ NMR (300 MHz, CDC13) d 8.16 (d, J = 5.8 Hz, 1H), 8.00 (s, 1H), 7.74 - 7.85 (m, 3H), 4.76 (s, 2H), 3.56-3.64 (m, 4H), 3.47 - 3.56 (m, 4H), 1.46 (s, 9H); MS (ESI +) for C25H25Fc 304S2 ia / z 610 (M + H) +. HPLC 73%, RT = 2.36 min (YMC ODS AQ, 33x3 mm, 10-90% acetonitrile in 3 min EXAMPLE 110 2- {[2, 5- bis < Trifluoromethyl) benzyl] sulfonyl hydrochloride} 4-piperazin-1-ylthieno [3, 2-c] pyridine The BOC group was removed from 4- (2. {[2,5- (trifluoromethyl) -benzyl] sulfonyl} thieno [3, 2]. -c] pyridin-4-yl) piperazin-1-tert-butyl carboxylate using < Method R. Product, 0.024 g (100%). White solid. 1 H NMR (300 MHz, DMSO-d 6) d 9.30 (s, 1 H), 8.25 (s, 1 H) H), 8.1 9 (d, J = 5.5 Hz, 1 H), 8.00-8.07 (m, 2 H), 7.8 5 (s, 1 H), 7.69 (d, J = 5. 5 Hz, 1 H) , 5.22 (s, 2 H), 3.24-3.3 3 (m, 4 H); MS (ESI +) for C20H.nF6N3O2S2.ClH m / z 510 (M + H) +. HPLC 90%, RT = 1.08 min (Y C ODS AQ, 33x3 mine, 30-60% acetonitrile in 1.5 min). INTERMEDIARY 85 4-. { 2- [(4-methylbenzyl) sulfonyl] thieno [3,2-c] pyridin-4-yl} piperazin-1-tert-butyl carboxylate

[0000] 4-Chloro-thieno [3,2-c] pyridin-2-sulfinate lithium (0.44 mol) was treated with 4-methylbenzyl bromide (0.59 mmol) as described in Method P above and then further reacted with tert-butyl piperazine-1-carboxylate as described in Method Q. Product 0.005 g (3% in the two steps). Solid beige. ½ MR (300 MHz, CDC13) d 8.15 (d, J = 6 Hz 1 H), 7.40 (s, 1 H), 7.00-7.16 (m, 4 H), 4.42 (s, 2 H), 3.46-3.60 (m, 4 H), 3.37-3.46 (m, 4 H), 2.34 (s, 3 H), 1.49 (s, 9 H); MS (ESI +) for C 24 H 29 N 3 O 4 S 2 m / z 488 (M + H) +. HPLC 69%, RT = 2.06 min (YMC ODS AQ, 33x3 inm, 10-90% acetonitrile in 3 min) EXAMPLE 11 2- [(4-Methylbenzyl) sulfonyl] -4-piperazin-1-ylthieno [2] hydrochloride 2-c] pyridine The BOC protecting group of 4- {2- 2- [(4-methylbenzyl) sulfonyl] thieno [3,2-c] pyridin-4-yl}. Piperazine-1-carboxylate of ter is removed. - Butyl using Method R. Product 0.05 g (75%) White solid XH NR (300 MHz, DMSO-d6) d 9.18 (s, 1 H), 8.17 (d, J = 5.5 Hz, 1 H), 8.01 (s, 1 H),? 6 (d, J = 5.5 Hz, 1 H), 7.38 (s, 1 H), 7.19 (s, 1 H), 7.11 (s, 1 H), 7.00 ( s, 1 H), 4.86 (s, 2 H), MS (ESI +) for C19H21N3O2S2, C1H m / z 388 (M + H) +, HPLC 90, RT = 1.65 min (ACE3 C8 50x3.0, mm, 10-97% acetonitrile in 3 min.) INTERMEDIARY 86 4- (2- { [5- Chloro-2- (trifluoromethyl) benzyl] sulfonyl.] Thieno [3,2-c] pyridin-4-yl) tert-butyl piperazin-1-carboxylate 4-chlorothieno [3,2-c] pyridin-2-sulfinate lithium (0.44 min.) was treated with 5-chloro-2- (trifluoromethyl) benzyl bromide or (0.59 immoles) as described in Method P above and then further reacted with tert-butyl piperazin-1-carboxylate as described in Method Q. Product, 0.019 g (7.5% in the two steps). Solid beige. ¾ NMR (300 MHz, CDC13) d 8.12- 8.14 (m, 1H), 7.80-7.88 (m, 2 H), 7.47-7.66 (m, 2 H), 4.71 (s, 2 H), 3.74-3.83 ( m, 4 H), 3.63-3.72 (m, 4 H), 1.49 (s, 9 H); MS (ESI +) for C 24 H 25 ClF 3 N 3 O 4 S 2 m / z 576 (M + H) +. HPLC 74%, RT = 2.30 min (YMC ODS AQ, 33x3 mm, 10-90% acetonitrile in 3 min). EXAMPLE 112 2- Hydrochloride. { [5- Chloro-2- (trifluoromethyl) benzyl] sulfonyl} 4-piperazin-1-ylthieno [3,2-c] pyridine The BOC group was removed from 4- (2. {[[5-chloro-2- (trifluoromethyl) benzyl] sulfonyl} thieno [3, 2-c] pyridin-4-yl) piperazin-1-yl-carboxylic acid tert-butyl ester using Method R. Product 0.012 g (92%). White solid. ¾ NMR (300 MHz, DMSO-d6) d 9.05 (s, 1 H), 8.18-8.23 (m, 2 H), 7.78-7.83 (m, 1 H), 7.72-7.76 (m, 1 H), 7.69 (d, J = 5.5 Hz, 1 H) r 7.62-7.65 (m, 1 H), 5.07 (s, 2 H), 3.65-3.72 (m, 4 H), 7.25-7.34 (m, 4 H); MS (ESI +) for Ci9H1 ClF3N302S2.ClH m / z 476 (M + H) +. HPLC 90%, RT = 1.65 min (ACE3 C8 50x3.0 mm, 10-97% acetonitrile in 3 min). INTERMEDIARY 87 4-. { 2- [(3,5-dimethoxybenzyl) sulfonyl] thieno [3,2-c] pyridin-4-yl} piperazin-1-tert-butyl carboxylate 4-chlorothieno [3,2-c] pyridin-2-sulfinate lithium (0.44 mol) was treated with 3,5-dimethoxybenzyl bromide (0.59 mol) as described in the Method P above and then further reacted with tert-butyl piperazine-1-carboxylate as described in Method Q. Product, 0.02 g (10% in the two steps). Solid beige. ? NMR (300 MHz, CDC13) d 8.14-8.18 (m, 1 H), 7.55 (s, 1 H), 6.40-6.45 (m, 1 H), 6.26-6.34 (m, 2 H), 4.39 (s, 2 H), 3.54-3.72 (m, 14 H), 1.50 (s, 9 H); MS (ESI +) for C25H3iN306S2 m / z 534 (M + H) +. HPLC 69% f RT = 1.99 min (YMC ODS AQ, 33x3 min, 10-90% acetonitrile in 3 min). EXAMPLE 113 2- [(3,5-Dimethoxybenzyl) sulfonyl] -4-piperazin-1-ylthieno [3,2-c] pyridine hydrochloride The BOC group of 4 was removed. { 2- [(3,5-dimethoxybenzyl) sulfonyl] thieno [3,2-c] pyridin-4-yl} piperazin-1-tert-butyl carboxylate using Method R. Product 0.01 g (62%). White solid. ¾ NMR (300 MHz, DMSO-d6) d 9.09 (s, 1H) 8.18 (d, J = 6. 7 Hz, 1H), 8.02 (s, 1H), 7.69 (d, J = 6.7 Hz, 1H),. 6.45-6.48 (m, 1H), 6.35-6.38 (m, 2H), 4.84 (s, 2H), 3.61-3.67 (m, 4H), 3.58 (s, 6H), 3.24-3.33 m, 4H). MS (ESI +) for C20H22N3O4S2 m / z 434 < M + H) +. HPLC 90%, RT = 1.60 min (ACE C8 50 x 30 mm, 10-97% acetonitrile in 3 min). EXAMPLE 114 2- [(2-Naphthylmethyl) sulfonyl] -4-piperazin-1-ylthieno [3,2-c] pyridine hydrochloride. 2- (Bromomethyl) naphthalene was used according to Method P-R to give 12.4 mg of the desired product.

½ NMR (270 MHz, CH3OH-d6) d ppm (obscured by C¾OH, 4H) 3.70-3.79 (m, 4 H) 4.95 (s, 2 H) 7.36-7.58 (m, 3 H) 7.70-7.91 (m, 6 H) 8.02 (d, J = 6.60 Hz, 1 H). LMS (M + 1) 424. EXAMPLE 115 4- Piperazin-1-yl-2- hydrochloride. { [4- (1, 2, 3-thiadiazol-4-yl) benzyl] sulfonyl} thieno [3,2-c] pyridine. 4- [4- (Bromomethyl) phenyl] -1,2,3-thiadiazole was used in accordance with Method P-R, to give 4.8 mg of the desired product. ½ NMR (270 MHz, C¾OH-d4) d ppm 3.41-3.50 (m, 4 H) 3.54 (s, 2 H) 3.89-3.98 (m, 4 H) 7.45 (d, J = 8.44 Hz, 2 H) 7.75 (d, J = 6.33 Hz, 1 H) 7.96- 8.13 (m, 4 H) 9.31 (s, 1 H). MS (M + 1) 458. EXAMPLE 116 1- (4-pyrrolidin-1-ylphenyl) -2- [(4-piperazin-1-ylthieno [3,2-c] pyridin-2-yl) sulfonyl] hydrochloride] Ethanone 2- bromo-1- (4-pyrrolidin-1-ylphenyl) ethanone was used according to Method PR to give 19.6 mg of the desired product. ½ NMR (270 MHz, C¾0H-d4) d ppm 2.02-2.12 (m, 4 H) 2.69 (s, 1 H) 3.37 (t, J = 6.73 Hz, 4 H) 3.54 (s, 1 H) 3.56.3.64 (m, 4 H) 4.12-4.22 (m, 4 H) 6.55 (d, J = 8.97 Hz, 2 H) 7.78-7.90 (m, 3 H) 8.03 (d, J = 6.86 Hz, 1 H) 8.41 ( s, 1 H). MS (M + 1. +. 471. EXAMPLE 117 1- [4- (Diethylamino) phenyl] -2- [(4-piperazin-1-ylthieno [3,2-c] pyridin-2-yl] hydrochloride] sulfonyl] ethanone 2-bromo-1- [4- (diethylamino) phenyl] ethanone was used according to Method PR to give 9.0 g of the desired product. ½ NMR (500 MHz, CH30H-d) d ppm 1.16 (t, J = 7.06 Hz, 6 H) 3.49-3.66 (m, 10 H) 4.14-4.27 (m, 4 H) 7.13 (br.s, 2 H) 7.85 (d, J = 6.59 1 Hz, 1 H) 7.98 (d, J = 8.48 Hz , 2 H) 8.03 (d, J = 6.59 Hz, 1 H) 8.47 (s, 1 1-1). MS (M + 1) 473. EXAMPLE 118 l- (4-bromophenyl) -2- [(4-piperazin-1-ylthieno [3,2-c] pyridin-2-yl) sulfonyl] ethanone 2- bromine was used 1- (4-bromophenyl) ethanone according to Method A, to give 3.4 mg of the desired product. ½ NMR (270 MHz, C¾0H-d4) d ppm 3.55 (s, 2 H) 3.56- 3.67 (m, 4 H) 4.08-4.26 (m, 4 H) 7.68 (d, J = 8.44 Hz, 2 H) 7.79 -7.98 (m, 3 H) 8.06 (d, J = 6.60 Hz, 1 @ H) 8.45 (s, 1 H). MS (M + 1) 481. EXAMPLE 119 l- (3-methoxyphenyl) -2- [(4-piperazin-1-ylthieno [3,2-c] pyridin-2-yl) sulfonyl] ethanone 2-bromine was used 1- (3-methoxyphenyl) ethanone according to Method A to give 1.0 mg of the desired product. aH NMR (270 MHz, C¾OH-d4) d ppm 3.54 (s, 2 H) 3.55-6.62 (m, J = 10.03 Hz, 4 H) 3.82 (s, 3 H) 4.06-4.18 (m, 4 H) 7.20 (dd, J = 8.05, 2.24 Hz, 1 H) 7.34- 7.49 (m, 2 H) 7.57 (d, J = 7.39 Hz, 1 H) 7.84 (d, J = 6.60 Hz, 1 H) 8.06 (d, J = 6.60 Hz, 1 H) L! .41 (s, 1 H). MS (M + 1) 432. EXAMPLE 120 1-phenyl-2- [(4-piperazin-1-ylthieno [3,2-c] pyridin-2-yl) sulfonyl] ethanone 2-broithio-1-phenylethanone was used. according to Method A to give 1.2 mg of the desired product. 1 H NMR (270 MHz, CH 3 OH-d 4) d ppm 3.55 (s, 2 H) 3.57- 3.66 (m, 4 H) 4.10-4.24 (m, 4 H) 7.46-4.57 (m, 2?) 7.66 ( t, J = 7.39 Hz, 1 H) 7.86 (d, J = 6.60 Hz, 1 H) 8.02 (dd, J = 14.12, 6.99 Hz, 3 H) 8.46 (s, 1 H). MS (M + l) 402.

Table 6 135 4- Piperazin-1-yl hydrochloride. { [2- ... j. F (trrHuoromethyl) phenylsulfonyl} - 1H- \ i pyridine Reaction Scheme 8 Legends of Reaction Scheme 8: i) Ethylchloroformate, TEA, acetone, NaN3; ii) B 3N, DCM and diphenyl ether; iii) P0C13, NaOH; iv) amines protected with BOC (R4), 2CO3, DMSO; v) H3 Na gas, H4C1, THF vi) sulfonyl chlorides (R1), NaH, THF; vii) HCl / diethyl ether, methanol. INTERMEDIARY 88 (2E) - 3- (1-benzyl-1H-pyrrol-2-yl) acryloyl azide To a mixture of 1-benzyl-1H-pyrrol-2-carbaldehyde (28.4 g, 0.125 mol) and TEA (13.5 ml) , 0.187 moles) in acetone (300 ml) was added dropwise ethylchloroformate (17.9 ml), 0.87 moles). The reaction was stirred for 1.5 hours after which NaN3 (13 g, 0.200 mole) in H20 (100 mL) was added. After 2 hours, the reaction was diluted with water and left overnight. The acetone was removed and the product separated by filtration to give 21.4 g of a slightly brown solid. This compound was taken for the next stage. INTERMEDIARY 89 1- Benzyl-1,5-dihydropyrrolo [3,2-cjpyridin-4-one was prepared by means of the literature procedure in accordance with C. Ducrocq; E. Bisangi; J-M, Lhoste; J. Mispelter; Tetra Edron, Vol. 32, pages 773-780, (1976) To a stirred solution of n-tributylamine (30 ml) in diphenyl ether (150 ml) heated to 195 ° C, an acyl solution was slowly added over 30 minutes. azide dissolved in DCM (150 ml). The reaction mixture was stirred at 195 ° C for 1 hour and then cooled to room temperature. Pentane (1.0 1) and ether (1.0 1) were added to the reaction mixture and the precipitate was collected by filtration. The crude solid was triturated with ether to give 6.89 g (81%) of the pure product. Purity by HPLC > 95%; MS (ESI) m / z 225 (m + H); ½ NMR (DMSO-d6, 25 ° C, 270.16) d 10.84 (br s, 1H), 7.43- 7.14 (m, 6H), 7.00 (d, J = 7.12 Hz, 1H), 6.57-6.49 (m, 2H) ), 5.83 (s, 2H).

INTERMEDIARY 90 1-Benzyl-4-chloro-1H-indole P0C13 (3.11 mL, 33.4 mmol) was added to 1-benzyl-1,5-dihydro-4H-pyrrolo [3,2-c] pyridin-4-one ( 3.75 g, 16.7 mmol) and the reaction was stirred at 120 ° C for 2 hours. NaOH (1M) was added and the mixture was extracted with DCM three times. The organic layers were dried (MgSO, i), filtered and the solvent was removed. Flash chromatography (DCM / Heptane / MeOH 4: 15: 1) gave 1.17 g (29%) of product. The product was taken for the next stage. INTERMEDIARY 91 4- (1- Benzyl-1H-pyrrolo [3,2-c] pyridin-4-yl) piperazin-1-tert-butyl carboxylate A mixture of 1-benzyl-4-chloro-1H-indole (1.17 g, 4. 82 mmol), K2C03 (2.0 g, mmol) and Boc-piperazine (1.79 gf 9.64 mmol) in DMSO (75 ml) was stirred at 120 ° C for 48 hours. Additional Boc-piperazine (4 equivalents) was added and the reaction was run for another 48 hours. The reaction was diluted with ethyl acetate (200 ml) and the mixture was washed with several portions of water. Flash chromatography (DCM / MeOH / Heptane 4: 1: 15) gave 0.51 g of starting material and 0.38 g of product. XH NMR (CD3OD) d 7.87-7.85 (m, 1H), 7.25- 7.24 (m, 3H), 7.04-6.98 (m, 3H), 6.73-6.71 (m, 1H), 6.53-6.52 (m, 1H) , 5.19 (s, 2H), 3.63- 3.59 (m, 8H), 1.47 (s, 9H); MS (ESI) 393 (M + H) +; Purity (HPLC, ACE column) 95%). INTERMEDIARY 92 4- (1H-pyrrolo [3,2-c] pyridin-4-yl) piperazine-1-carboxylate of tert-butyl 4- (1-benzyl-1H-pyrrolo [3,2-c] pyridine was dissolved 4-yl) piperazin-1-tert-butyl carboxylate (383 mg, 0.488 mmol) in THF (6 mL) and liquid ammonia (10 mL) was added in a 30 mL vial, Na (67 mg) was added. , 2.93 mmole) in portions and the reaction turned violet. After 30 minutes NH 4 Cl (sat) was added and the reaction was left at room temperature. The THF was removed and the residue was extracted with DCM. Recrystallization (DCM / Heptane) gave 112 mg of a white solid. ¾ NM (CD3OD) d 8.66 (s, 1H), 7.89 (d, 1H, J = 5.80 Hz), 7.13 - 7.11 (m, 1H), 6.89 - 6.86 (m, 1H), 6.57 - 6.56 (m, 1H), 3.67 - 3.60 (m, 8H), 1.48 (s, 9H); MS (ESI) 303 (M + H) +; Purity (HPLC, ACE column) 95%. S method for sulfonylation: 4- (1H-pyrrolo [3,2- c] pyridin-4-yl) piperazin-1-tert-butyl carboxylate (total 1391 mmol, 1 equiv.) In THF (14 ml) was dissolved and it was dispensed in 10 ml bottles with a screw cap. A suspension of NaH (0.1488 mmol, 1.5 equiv.) In THF (15 ml) was eventually dispensed into the flasks containing the solution of 4- (1H-pyrrolo [3,2- c] pyridin-4-yl) piperazine- 1-tert-butyl carboxylate and stirred for approximately 15 minutes. Different sulforyl chlorides in THF (2 ml) were dissolved in each and exhausts were added to the reaction mixtures. The reactions were stopped with MeOH (100 μ?) And PS-Trisamine (3 equiv.) Was added to each vial and shaken for 2 hours. The mixtures were filtered and the filtrates were concentrated in vacuo. Products that were not pure enough (purity < 90%) were purified by preparative chromatography using acetonitrile-water gradients containing 0.1% trifluoroacetic acid. After the HPLC analysis the fractions that were > 90% pure n were collected and concentrated. T method of BOC deprotection; The Boc-protected compound was dissolved in MeOH (2 mL) and HCl / ether (2 mL) was added. After 45 minutes the solvent was removed. INTERMEDIARY 93 4- [1- (Phenylsulfonyl) -1H-pyrrolo [3,2- c] pyridin-4-yl] piperazin-1-tert-butyl carboxylate Purification by recrystallization gave 16 mg (56% after deprotection of Boc ¾ NMR (CDC13) d 8.03-8.01 (m, 1H), 7.89-7.86 (m, 2H), 7.57-7.39 (m, 5H), 6.67-6.64 (m, 1H), 3.55-3.52 (m, 5H), 1.47 (s, 9H), MS (ESI) 443 (M + H) +, Purity (HPLC), ACE column) 95%. INTERMEDIARY 94 4-. { 1- [(4-chlorophenyl) sulfonyl] -1H-pyrrolo [3,2- c] pyridin-4-yl} piperazin-1-tert-butyl carboxylate Purification by preparative HPLC gave 4 iag (11%) after deprotection of Boc. ¾ MR (CDC13) d 8.03-7.51 (m, 7H), 6.89-6.87 (m, 1H), 3.91-3.66 (m, 8H), 1.47 (s, 9H); MS (ESI) 377 (M + H) +; Purity (HPLC, ACE column) 95%. INTERMEDIARY 95 4-. { 1- [(4-methoxyphenyl) sulfonyl] -1 H- pyrrolo [3,2-c] pyridin-4-yl} piperazin-1-tert-butyl carboxylate Purification by recrystallization (MeOH / ether) gave 21 mg (67%) after deprotection of boc. ?? NMR (CDCl 3) d 8.02-8.00 (m, 1H), 7.84-7.80 (m, 2H), 7.48-7.46 (m, 1H), 7.41-7.38 (m, 1H), 6.92-6.86 (m, 2H), 6.64-6.62 (m, 1H), 3.79 [s, 3HJ, 3.57-3.52 (m, 8H), 1.48 (s, 9H); MS (ESI) 473 (M + H); Purity (HPLC, ACE column) 95%. INTERMEDIARY 96 4- (1- { [2- (trifluoromethyl) phenyl] sulfonyl} -. 1 H -pyrrolo [3,2-c] pyridin-4-yl) piperazin-1-tert-butyl carboxylate Purification Preparative HPLC gave 8.6 mg (25%) after deprotection of boc. ½ MR (CDCI3) d 8.14-8.11 (m, 1H), 8.01-7.94 (m, 2H), 7.89-7.72 (m, 3H), 7.37-7.34 (m, 1H), 6.89-6.88 (m, 1H) , 3.93-3.89 (m, 4H), 3.71-3.67 (m, 4H), 1.47 (s, 9H); MS (ESI) 511 (M + H) +; Purity (HPLC, ACE column) 95%. INTERMEDIARY 97 4-. { 1- [(2-methoxy-5-methylphenyl) sulfonyl] -1H-pyrrolo [3,2-c] pyridin-4-yl} piperazin-1-carboxylate Purification by preparative HPLC gave 10.3 mg (32%) after deprotection of boc. ¾ NMR, (CDCl 3) d 7.95-7.92 (m, 2H), 7.74-7.72 (m, 1H), 7.44-7.40 (m, 2H), 6.85-6.77 (m, 2H), 3.92-3.88 (m, 4H ), 3.70 (s, 3H), 3.69-3.66 (m, 4H), 2.39 (s, 3H), 1.47 (s, 9H); MS (ESI) 487 (M + H) +; Purity (HPLC, ACE column) 95%. EXAMPLE 121 4- Piperazin-1-yl-1- (toluene-4-sulfonyl) -1H-pyrrolo [3,2-c] pyridine hydrochloride p-Toluenesulfonyl chloride (24.6 mg) was added at 4- (1H- pyrrolo [3, 2-c] pyridin-4-yl) piperazine-1-carboxylic acid tert-butyl ester, the title compound (4.3 mg). LC / MS RT: 1374 (System 10 up to 40% MeCN for 1.5 min, ACE C8), Purity, 91%. MS: 357 (M + 1).

¾ NMR (CD3OD) d ppm 2.39 (s, 3.H) 3.48 (m, 4 H) 4.06 (m, 4 H) 7.22 (d, J = 3.71 Hz, 1 H) 7.43 (d, J = 8.16 Hz, 2 H) 7.95 (m, 5 H). EXAMPLE 122 1- (3-Chloro-2-methyl-benzenesulfonyl) -4- piperazin-1-yl-1H-pyrrolo [3,2-cjpyridine] hydrochloride 3-Chloro-2-methylbenzenesulfonyl chloride (29.0 mg) to 4- (1H-pyrrolo [3,2-c] pyridin-4-yl) piperazin-1-tert-butyl carboxylate, the title compound (6.3 mg). LC / MS RT: 1.563 (System 10 up to 40% MeCN for 1.5 minutes, ACE, C8), purity, 96%. MS: 392 (M + 1). EXAMPLE 123 1- (3,4-Dimethoxy-benzenesulfonyl) -4- piperazin-1-yl-1H-pyrrolo [3, 2-c] pyridine hydrochloride 3,4-dimethoxybenzenesulfonyl chloride (30.5 mg) was added to 4 - (1 H) - tert-butyl pyrrolo [3,2- c] pyridin-4-yl) piperazin-1-carboxylate, the title compound (8.5 mg). LC / MS RT: 1.284 (System 10 up to 40% MeCN for 1.5 minutes, ACE C8), Purity, 92%. MS: 404 (M + l). 1H NMR (CD3OD) d ppm 3.50 (m, J = 4.21 Hz, 2H) 3.85 (d, J = 3.22 Hz, 4 H) 4.10 m, J = 3.96 Hz, 2 H) 7.11 (d, J = 8.66 Hz, 1 H) 7.23 (d, J = 3.46 Hz, 1 H) 7.48 (d, J = 1.73 Hz, H) 7.74 (dd, J = 8.54, 1.86 Hz, 1 H) 7.92 (s, 2 H) 8.07 (d , J = 3.46 Hz, 1 H). EXAMPLE 124 4- (4-Piperazin-1-yl-pyrrolo [3,2-c] pyridin-1-sulfonyl) -benzonitrile hydrochloride 4-Cyanobenzenesulfonyl chloride (26.0 mg) was added to 4- (1H-pyrrolo [ 3, 2-c] pyridin-4-yl) piperazine-1-carboxylic acid tert-butyl ester, the title compound (9.1 mg). LC / MS R: 1150 (System 10 up to 40% MeCN for 1.5 minutes, ACE C8), Purity. 93% MS: 3.69 (M + l) 1H NMR (CD3OD) d ppm 3.50 (m, 4 H) 4.08 (m, 4 H) 7.29 (d, J = 3.71 Hz, 2 H) 7.98 (, 4 H) 8.29 [f J = 8.66 Hz, 2 H) .

EXAMPLE 125 1- (4,5-Dichlorothiophene-2-sulfonyl) - 4-piperazin-1-yl-1H-pyrrolo [3,2-c] pyridine hydrochloride 4-5-Dichlorothiophene-2-sulfonyl chloride (32.4 mg) was added to 4- (lH-pyrrolo [3,2- c] pyridin-4-yl) piperazin-1-tert-butyl carboxylate, the compound of the title (0.3 mg). LC / MS RT: 1.119 (System 10 up to 40% MeCN for 1.5 minutes, ACE C8), Purity, 92 S. MS: 418 (M + l). EXAMPLE 126 1- (2-Chloro-4-fluoro-benzenesulfonyl) -4- piperazin-1-yl-1H-pyrrolo [3,2-c] pyridine hydrochloride 2-Chloro-4-fluorobenzenesulfonyl chloride (29.5) mg) was added to 4- (1H-pyrrolo [3,2-c] pyridin-4-yl) piperazin-1-tert-butyl carboxylate, the title compound (2.4 mg). LC / MS RT: 1.361 (System 10 up to 40% MeCN for 1.5 minutes, ACE C8), Purity, 90%. MS: 396. ¾ MR (CD3OD) d ppm 3.51 (m, 4 H) 4.08 (m, 4 H) 7.23 (dd, J = 3.96, 0.49 Hz, 1 7.47 (m, 1 H) 7.55 (dd, J = 8.41, 2.47 Hz, 2 H) 7.62 (d, J = 6.93 Hz, 1 H) 7.91 (d, J = 7.18, 1 H) 8.06 (d, J = 3.96 Hz, 1 H) EXAMPLE 127 Hydrochloride 1- Phenylmetanesulfonyl-4-piperazin-1-yl-1H-pyrrolo [3,2-c] pyridine. Phenylmethanesulfonyl chloride (24.6 mg) was added to 4- (lH-pyrrolo [3,2-c] pyridin-4-). il) tert-butyl piperazine-1-carboxylate, the title compound (0.2 mg), LC / MS, RT: 1.007 (System 10 up to 40% MeCN for 1.5 minutes, ACE C8), Purity, 90%, MS : 357 (M + l).

EXAMPLE 128 1- (5-Chloro-thiophene-2-sulfonyl) -4-piperazin-1-yl-1H-pyrrolo [3,2-c] pyridine hydrochloride 5-chlorothiophen-2-sulfonyl chloride (28.0) mg) to 4- (1H-pyrrolo [3,2- c] pyridin-4-yl) piperazin-1-tert-butyl carboxylate, the title compound (7.2 mg). LC / MS RT: 1.381 (System 10 up to 40% MeCM for 1.5 minutes, ACE C8), Purity, 97%, MS: 483 (M + l). EXAMPLE 129 1- (4-Butyl-benzenesulfonyl) -4-piperazin-1-yl-1H-pyrrolo (3, 2-c) pyridine hydrochloride 4-N-butylbenzenesulfonyl chloride (30.0 mg) was added at 4- ( 1H- tert-Butyl pyrrolo [3, 2-c] pyridin-4-yl) piperazin-1-carboxylate, the title compound (11.9 mg). LC / MS, RT: 1904 (System 10 up to 40% MeCN for 1.5 minutes, ACE C8), Purity, 95%, MS: 400 (M + l).

LH NMR (CD30D) d ppm 0.90 (t, J = 7. 8 Hz, 3 H) 1.31 (m, 2 H) 1.55 (m, 2 H) 2.67 (m, 2 H) 3.50 (m, 4 H) 4.09 (m, J = 3.96 Hz, 4 H) 7.25 (d, J = 3.71 Hz, 2 H) 7.44 (d, J = 8.16 Hz, 2 H) 7.91 (m, 2 H) 8.02 (m, 2 H). EXAMPLE 130 1- (4-Phenoxy-benzenesulfonyl) -4-piperazin-1-yl-1H-pyrrolo (3,2-c) pyridine hydrochloride (4-phenoxy) benzene) sulfonyl chloride (34.7 mg) was added to 4- (1H- pyrrolo [3,2- c] pyridin-4-yl) piperazin-1-tert-butyl carboxylate, the title compound (12.8 mg). LC / MS RT: 1839 (System 10 up to 40% MeCN for 1.5 minutes, ACE C8), Purity, 95%. MS: 436 (M + 1). to? NMR (CD3OD) d ppm 3.50 (m, J = 3.96 Hz, 4 H) 4.09 (m, J-4.45 Hz, 4 H) 7.05 (dd, J = 8. 16, 6.43 Hz, 2 H) 7.26 (m, 2 H) 7.44 (t, J == 7.79 Hz, 2 H) 7.90 (m, 3 H) 8.01 (d, J = 3.71 Hz, 2 H) 8.07 (d, J = 8.91 Hz, 2 H). EXAMPLE 131 1- (Phenylsulfonyl) -4- piperazin-1-yl-1H-pyrrolo [3,2-c] pyridine hydrochloride Purification by recrystallization gave 16 mg (56%) after deprotection of Boc. MS (ESI) 343.1 (M + l) +; purity (HPLC, ACE column), 94%). EXAMPLE 132 1- [(4-Chlorophenyl) sulfonyl] -4-piperazin-1-yl-1H-pyrrolo [3/2-c] pyridine hydrochloride Purification by preparative HPLC gave 4 mg (11%) after deprotection of Boc. MS (ESI) 377 (M + H) +; Purity (HPLC, ACE column), 96%). EXAMPLE 133 Hydrochloride of 1- [(4-methoxyphenyl) sulfonyl] -4-piperazin-1-yl-1H-pyrrolo [3,2-c] pyridine Purification by recrystallization (MeOH / Ether) gave 21 mg (67%) ) after deprotection of Boc. MS (ESI) 373 (M + H) + Purity (HPLC, ACE column), 92%. EXAMPLE 134 1- [(2-Methoxy-5-methylphenyl) sulfonyl] -4- piperazin-1-yl-1H-pyrrolo [3, 2-c] pyridine hydrochloride Purification by preparative HPLC gave 10.3 mg (32%) after deprotection of Boc. MS (ESI) 387 (M + 1) +; Purity (HPLC, ACE column), 95%. EXAMPLE 135 4- Piperazin-1-yl-1- Hydrochloride. { [2- . { trifluoromethyl) phenyl] sulfonyl} - 1H- pyrrolo [3,2-c] pyridine Purification by preparative HPLC gave 8.6 mg (25% after deprotection of Boc, MS (ESI) 411 (M + H) +; Purity (HPLC, column ACE), 94 % BIOLOGICAL TESTS The ability of a compound according to the invention to bind to the 5-HT6 receptor, and to be pharmaceutically useful, can be determined using in vivo and in vitro assays known in the art.Material Cell culture The HEK cell line -293 transfected with the 5-HT6 receptor was cultured in Dulbeccos Modified Eagles Medium containing 5% dialyzed fetal bovine serum, (Gibco BRL 10106-169), 0.5 mM sodium pyruvate and 400 μg Geneticin (G- 418) (Gibco BRL10131-019) Cells were passed 1:10, twice a week Chemicals The radioligand [¾] LSD60-240 Ci / mmol, obtained from Amersham Pharmacia Biotec, (Buckinghamshire, England) was in ethanol and was stored at -20 ° C. Unlabelled ligands, representing different selectivity profiles, are presented n in Table 1. Compounds were dissolved in 100% DMSO and diluted with binding buffer. Dispositions The compounds were diluted in 96-well plates of V-costar bottom polypropylene (Corning Inc. Costar, ??, USA). The samples were incubated in Packard OptiPlate (Packard Instruments B.V., Groningen, The Nedtherlands). The total amount of radioligand added was measured in Packard 96-well Barex plates (Packard Instruments B.V., Groningen, The Netherlands) in the presence of Microscint ™, 20 Twinkle Packard Bioscience fluid, Meriden, CT, USA). Regulator The binding regulator consisted of 20 M of HEPES, 150 mM of NaCl, 10 mM of MgCl2, and 1 mM of EDTA, pH, 7.4. Methods Membrane preparation Cells were grown to approximately 90% confluence on 24.5 x 24.5 UC culture plates. The medium was aspirated, and then rinsed with ice-cold PBS, the cells were removed by scraping using 25 ml of regulator. Tris (50 mM Tris-HCl, 1 mM EDTA, 1 mM EGTA, pH 7.4) and a window scraper. The cells were fragmented with a Polytron homogenizer, and the remaining particulate matter was removed by low speed centrifugation, 1000 x g for 5 minutes. Finally, the membranes were collected by high speed centrifugation (20,000x g), suspended in the binding buffer, and frozen in aliquots at -70 ° C. Radioligand binding Frozen cell membranes were thawed, immediately re-homogenized with a Polytron homogenizer, and coupled to SPA wheat germ agglutinin beads (Amersham Lie Sciences, Cardiff, England) for 30 minutes under continuous tube agitation. . After coupling, the beads were centrifuged for 10 minutes at 1000 g, and subsequently suspended in 20 ml of binding buffer per 96-well plate. The binding reaction was then initiated by the addition of the radioligand and the test compounds to the membrane-bead suspension. After incubation at room temperature, the test plates were subjected to scintillation counting. The original SPA method was followed, except that the membranes were prepared from HE 293 cells expressing the human 5-HT6 receptor instead of HeLa cells (Dinh DM, Zaworski PG, Gili GS, Schlachter SK, La son CF, Smith M. Validation of human 5-HT6 receptors expressed in HeLa cell membranes: saturation binding studies, pharmacological profiles of standard CNS agents and SPA development, Technical Report No. 7295-95-064 1995 of Upjohn Company; December 27) . The specific binding of [3H] LSD was saturable, whereas the non-specific binding increased linearly with the concentration of the added radioligand. [3H] LSD linked with high affinity to the 5-HT6 receptors. The value of ¾ was estimated 3n 2.6 ± 0.2 nM based on four separate experiments. The total link to 3 nM of [3H] LSD, the radioligand concentration used in the comparative experiments was typically 6000 dpm, and the specific binding more than 70%. 5-HT caused a concentration-dependent inhibition of [3H] LSD with a value of ¾. average total of 236 nM when tested against two different membrane preparations. The inter-variability test in 3 experiments showed a CV of 10% with an average valor value of 173 nM (SD 30) and a Hill coefficient of 0.94 (SD 0.09). The inter variation test was 3% (n = 4). The values of i for a limited group of reference compounds with binding affinities reported to the 5-HT6 receptor are presented in Table 7. All the unlabeled ligands showed the specific binding of [3 H] LSD in a manner dependent on the concentration, although at different powers. The order in the power levels for the compounds was metiotepin (2 nM) >; mianserin (190 nM) «5 -HT (236 nM) > methysergide (482 nM) > mesulergida (1970 nM). Protein determination Protein concentrations were determined with BioRad Protein Assay (Bradford MM). A quick and simple method for the quantification of amounts in micrograms of protein using the principle of the dye-protein link. anal. Biochem 1976; 2: 248-54). Bovine serum albumin was used as standard. Scintillation Counting Radioactivity was determined in a Packard TopCount ™ scintillation counter (Packard Instruments, Meriden, CT, USA) with a counting efficiency of approximately 20%. The efficiency of the count was determined in separate groups of experiments. Saturation experiments At least 6 concentrations were used in duplicate radioligand (0.1-20 nM [3H] LSD in the saturation experiments.) The specific binding was calculated as the difference between the total bond and the non-specific binding, which was determined as the radioligand binding in the presence of 5 uM of lisuride, BmaK and the dissociation constant, ¾, were determined from non-linear regression analysis using equation 1.

Lu, is the concentration of radioligand without binding, and y is the quantity bound. y = [(Bmax) Lu] / (Lu + Kd) (Equation 1) The total and non-specific linkage of the radioligand was defined in eight replicates of each. The samples containing the test compound were run at room temperature for 3 hours. The IC 50 value, that is, the concentration of test compound that inhibited 50% of the radioligand specific binding, was determined by non-linear regression analysis and the value of i was calculated using the method of the [Cheng YC Biochem. . Pharmacol. 22, 3099-3108, 1973S] Equation 2. i = IC50 / [1+ (L / Kd)] (Equation 2) (b) Intrinsic Activity Assay of 5 ~ HT6 Antagonists to the 5-HT 6 receptor were characterized by measurement of the inhibition of the induced increase in HT in C¾MP in HEK 293 cells expressing the human 5-HT 6 receptor (see Boess et al. (1977) Neuropharmacology 36: 713-720.) In summary, HEK293 / 5-HT 6 cells were seeded in 96-well plates coated with polylysine at a density of 25,000 / well and developed in DMEM medium (Dulbecco's Modified Eagle Medium) (without phenol red) containing 5% of dialyzed Fetal Bovine Serum for 48 hours at 37 ° C in a C02 to 5 incubator. % The medium was aspirated and replaced by 0.1 ml of assay medium (Hank Balance Salt Solution containing 20 mM HEPES, 1.5 mM isobutylmethylxanthine and 1 mg / ml bovine serum albumin) After addition of the substances test, 50 μ? were dissolved in assay medium, the cells were incubated for 10 minutes at 37 ° C in an incubator with 5% C02. The medium was again aspirated and the content of CñMP determined using a radioactive cAMP kit (Amersham Pharmacia Biotech, BIOTRAK RPA559). The potency of the antagonists was quantified by determining the concentration that caused 50% inhibition of 5-HT (a [5-HT] = 8 times EC5o) evoked the increase in cAMP, using the formula IC5o, corr = IC50 / (1+ [5HT] / EC50) - The compounds according to the invention have a selective affinity towards 5-HT6 receptors with Ki and IC50 values between 0.5 nM and 5 μo or have a% inhibition of [3H] LSD > 20% at 50 nM and are antagonists, agonists or partial agonists at 5-HT6. The compounds show good selectivity on 5-HTia, 5-HT2a / 5-HT2b / - (c) In vivo tests of reduction of dietary intake For a review on serotonin and dietary intake, see Blundell, J. E. and Halford, J. C. G. (1998) Serotonin and Appetite egulation. Implications for the Pharmacological Treatment of Obesity. CNS Drugs 9: 473-495. Obese mice (ob / ob) were selected as the primary animal model to discriminate how their mutant mice consume high amounts of feed resulting in a high signal in proportion to the background. To further substantiate and compare the efficiency data, the effect of the compounds on food consumption in wild-type mice was also studied (C57BL / 6J) The amount of food consumed during 15 hours of infusion of the compounds was recorded. in all studies male mice (C57BL / 6Jbom-Lepob obese and C57Bl / 6Jbom of wild-type skinny; Bomholtsgaard, Denmark) of 8 - 9 weeks with an average body weight of 50 g (obese) and 25 g (skinny). The mice were housed individually in cages at 23 ± 1 ° C, 40-60% humidity and had free access to water and standard laboratory food. The 12/12 h light / dark cycle was adjusted to turn off lights at 5 p.m. The animals were conditioned for at least one week before beginning the study. The test compounds were dissolved in suitable solvents for each specific compound such as cyclodextrin, cyclodextrin / methanesulfonic acid, polyethylene glycol / methanesulfonic acid, saline. Newly prepared solutions were made for each study. Doses of 30, 50 and 100 mg / kg / day were used. The purity of the test compounds was of analytical grade. Animals were weighed at the beginning of the study and randomized based on body weight. The Alzet osmotic mini-pump (Model 2001D, at an infusion rate of 8 μ? / H) was used and loaded essentially as recommended by the Alzet Technical Information Manual (Alza Scientific Products, 1997; Theeu ea, F. y Yam, SI Ann, Biomed, Eng 4 (4), 343-353, 1976). Continuous subcutaneous infusion with 24 hours duration was used. The minipumps were filled either with different concentrations of test compounds dissolved in vehicle or only with vehicle solution and kept in pre-heated vehicle at 37 ° C (approximately 1 hour). The minipumps were implanted subcutaneously in the back region of the neck under short-term anesthesia (metofan / enflurane). This surgical procedure lasted approximately 5 minutes. It took approximately 3 hours to reach the stationary state of compound release. The weight of the food compacts was measured at 5 p.m. and at 8 p.m. for two days before (baseline) and one day after implantation of the osmotic minipumps. The internal weight was carried out with a Mettler Toledo PR 5002 scale supported by a computer. The occasional spill is corrected. At the end of the study the animals were killed by neck dislocation and blood samples were taken for further analysis of plasma drug concentrations. The proteins in the plasma sample were precipitated with methanol, centrifuged and the supernatant was transferred to HPLC flasks and injected into the mass spectrometric / liquid chromatography system. The mass spectrometer was adjusted for electrospray in positive ionic mode and Multiple Reaction Monitoring. A linear regression analysis of forced standards up to the origin was used to calculate the concentrations of the unknown samples. The food consumption was measured for 15 hours for the three consecutive days and the percentage values of the basal level were derived from each animal from the day before and after treatment. The values were expressed as mean + SD ± SEM of eight animals per dose group. Statistical evaluation by Kurskal-Wallis A OVA of one route was carried out using the values of the basal percentage. If the statistical significance is reached at the level of p < 0.05, Mann-Witney U-test was performed by statistical comparison between control and treatment groups. The compounds according to the invention showed an effect in the range of 5-200 mg / kg.

Table 7. Biological Data In vitro link to the human 5-HT6 receptor Efficiency data in vivo Example% Reduction Css, u (u) 1 12 0.44 11 47.1 0.02 40 44 0.2

Claims

NOVELTY OF THE. INVENTION Having described the present invention, it is considered as a novelty, and therefore the content of the following is claimed as property: CLAIMS: l.A compound of the general formula (I): or a pharmaceutically acceptable salt thereof, wherein: in ring B is wherein D is a 5-membered heteroaryl or heterocyclic ring, the heteroaryl ring comprises one or two atoms selected from the group consisting of nitrogen, sulfur and oxygen, with the proviso that D contains an oxygen atom, D is heteroaryl; each W is independently -N-, - (CH-, -C- provided that no more than three W groups are -N- in both A and B rings together, P is any one of formula (a), (b) ) or (c) where x = 0, 1, or 2 and y = 0, 1, or 2; and P and R3 can be attached to any carbon atom that allows substitution in one of the rings A- or B- or in both or when ring A contains at least one nitrogen atom and P is (c), then P it can be fixed to any nitrogen in ring B that allows substitution; the dashed links denote that P and R3, respectively, may be fixed to either ring A or B; but each of P or R3 may not be linked simultaneously to both rings A and B; R1 is (a) Ci-6-alkyl, (b) Ci_6-alkoxyalkyl (c) Ci-6-hydroxyalkyl straight or branched chain, (d) Ci-6-straight or branched chain alkylhalides, (e) aryl carbonylmethyl , (f) C3_7-cycloalkyl, which is optionally unsaturated, (g) Cs-T-cycloalkyl-Ci-e-alguyl, wherein the cyclic ring is optionally partially unsaturated, or (h) an Ar group wherein Ar is (a) phenyl, (b) 1-naphthyl, (c) 2-naphthyl, (d) aryl-Ci_6-alkyl, (e) cinnamyl (f) a heterocyclic mono- or bicyclic ring, partially saturated or fully saturated , optionally aromatic of 5-7 elements, each containing 1 to 4 heteroatoms, selected from oxygen, sulfur and nitrogen, (g) a bicyclic ring system comprising at least one heterocyclic ring in accordance with (f) and an Ar group. , wherein the group Ar is substituted in one or more positions with (a) H, X or?, or (b) a partially or fully saturated optionally aromatic heterocyclic ring of 5 to 7 elements, containing 1 to 4 heteroatoms selected from oxygen, nitrogen or sulfur; R2 is (a) H, (t>) Ci_6-alkyl, (c) C2-6-alkoxyalkyl, (d) Ci-6-hydroxyalkyl straight or branched, or (e) Ci-6-straight or branched alkylhalides; (f) a group Ar, or R1 and R2 are linked to form a group -C¾- CH2-0-CH2-CH2- or where v is 0-2, X and Y are independently (a) H, (b) halogen, (c) Ci-6-alkyl, (d) CF3, (e) hydroxy (f) Ci-6-alkoxy, (g) C2-6-alkenyl, (h) phenyl, (i) phenoxy, (j) benzyloxy, (k) benzoyl, (1) -OCFs, (m) -CN, (n) straight or branched Ci_6hydroxylalkyl, ( o) Ci-6-straight or branched alkylhalides, (P) - ¾, (q) -NHR4, (r) -NR4R5, (5) -N02 / (t) -CONR4R5, (u) -NHSO2R4, (v) -NRCOR5, (x) -S02NR4R5, (z) -C (= 0) R4, (aa) -C02R4, 0 (ab) -S (0) nR4 / where n is 0, 1, 2 0 3, ( a) -S- (Ci_6) alkyl, 0 (ad) -SCF3; and R4 and R5 are independently (a) H, (b) Ci-5-alkyl, (c) C3_7-cycloalkyl, 0 (d) Ar, as defined above for R1; alternatively, R4 and R5 are linked to form a group -CH2OCH2-, -CH2CH2OCH2CH2- or (CH2) 3-5; R3 is a group selected from any one of wherein R is optionally substituted on each carbon atom that allows substitution with groups Rq, wherein Rq is independently H, or (Ci-6-alkyl, and wherein Rq groups may be present on the same carbon atom simultaneously, where q = 1, 2, 3, 4, 5 or 6, m = 1 or 2, and n = 0, 1 or 2, R6 is independently (a) H (b) Ci-6-linear or branched alkyl, ( c) benzyl (d) -CH2-CH2-OH, or (e) -CH2-CH2-0-Ci6-alkyl; P and R3 may be attached to the same ring or to different rings of rings A and B; that when P is and P and R3 are both fixed to ring A in the meta- or para- position in relation to one another, then R3 is selected from any one of where the B ring is (a), then P and are simultaneously fixed to the same ring A or I where the B ring is where y = 0, then P and RJ are fixed to the different rings A and B; when the ring system A + B is benzofuran or benzothiophene, and P is and it is fixed at position 3 in the annular system A + B, and R3 is a group selected from any one of and it is fixed in position 7 in the ring system A + B, then y = 1 or 2; when the annular system A + B is indole, and P is and P is fixed in position 3 in the annular system A + B, and 3 is a group selected from any one of and R3 is fixed in position in any one of positions 5, 6 or 7 in the ring system A + B, then y = and R1 = Ar is partially saturated bicyclic heterocyclic ring containing an atom of N in Ar can not be fixed to the S atom in P; with the proviso that when rings A and B are both phenyl, P is any one of formula (a) or (c) substituted at position 7 in the naphthalene ring, then R3 is not substituted in position 1 in the ring naphthalene; and with the proviso that: when ring D is a pyrrole ring, P is of formula (c), then R3 is not of the formula substituted in position 3 in the pyrrole ring. 2. The compound according to claim 1, characterized in that R1 is (a) cy-6-alkyl, or (e) an Ar group; Ar is (a) phenyl (b) 1-naphthyl, (c) 2-naphthyl, or (f) a partially or fully saturated, optionally aromatic heterocyclic ring of 5 to 7 elements containing 1 to 4 heteroatoms, selected from oxygen, nitrogen and sulfur, wherein the group Ar is substituted in one or more positions with (a) H (b) halogen (c) Ci-6-alkyl, (d) -CF3, (f) Ci-6-alkoxy, ( g) C2-6-alkenyl (preferably C2-4-alkenyl), (1) -OCF3, (m) Ci-.6-tLydroxyalkyl straight or branched, (n) phenyloxy, (o) benzyloxy, (v) -NRCOR5, (x) -S02NR4R5, (z) -C (= 0) R4, (ab) -S (0) nR * / wherein n is 0, 1, 2 or 3; (ac) -S- (Ci-e) -alkyl, or (ad) -SCF3 R2 is (a) H or (b) Ci-6-alkyl; or R1 and R2 are joined to form a group X and Y are H; R4 and R5 are independently from each other H or Ci alkyl; and R3 is selected from any one of wherein R3 can be substituted on each carbon atom that allows substitution with groups Rq, wherein Rq is independently H, or Cj-s-alkyl, and wherein two Rq groups can be simultaneously present on the same carbon atom, wherein q = 1 or 2, m = 1 or 2 n = 0, and R6 is independently (a) H, (b) Ca_6-alkyl (preferably Ci-3-alkyl), in particular methyl, (d) -CH2 -CH2-0H, or (e) -CH2-CH2-OCH3. 3. The compound according to claim 1 or 2 characterized in that R3 is selected from any one of carbon that allows substitution with Rg groups, where Rq is independently H, or Ci-2-alkyl, and wherein two Rg groups may be present on the same carbon atom simultaneously, where q = 1 or 2, m = 1 or 2; and R6 is independently (a) H, (b) Ci_3-alkyl, (d) -CH2CH2-0H, or 4. The compound according to claim 1 or 2, characterized in that R3 is selected from the group consisting of any one from wherein R3 can be substituted on each carbon atom that allows substitution with groups Rq, wherein Rq is independently H, or Ci_6_alkyl, and wherein two Rq groups can be simultaneously present on the same carbon atom, where q = 1 or 2, m = 1 or 2, n = 0, and R6 is independently (a) H, (b) Ci-3-alkyl, (d) -CH2-CH2-OH, or (e) -CH2-CH2 -OCH3. 5. The compound according to claim 1 or 2, characterized in that R3 is selected from any one of R6 is independently (a) H, (b) Ci_3-alkyl, or (d) -CH2-CH2-OH, or 6. A compound according to any one of claims 1 to 5 characterized in that R6 is H or methyl. 7. A compound according to claim 1 or 2 characterized in that R3 is piperazine; homopiperazine; 1,6-dimethylpiperazine; 3,5-dimethylpiperazine 2,5-dimethylpiperazine; 2-methylpiperazine; 3- methylpiperazine; 2, 2-dimethylpiperazine; 3, 3-dimethylpiperazine; piperidine; 1, 2, 3, 6-tetrahydro-pyrazine; or 4-pyrrolidin-3-yloxy. 8. The compound according to any one of claims 1 to 7, characterized in that the groups? and X are attached to any unsubstituted carbon atom. 9. The compound according to any one of claims 1 to 8, characterized in that D is pyrrolyl, thienyl or furanyl. 10. The compound according to any one of claims 1 to 9, characterized in that P is wherein R1, x, ey are as defined in claim 1. The compound according to any one of claims 1 to 9, characterized in that P is wherein R1 and R2 are as defined in claim 1. 12. The compound according to claim 11, characterized in that R2 is H. 13. The compound according to claim 10, characterized in that it has the general formula (II) wherein R1, x, y, X, and Y are as defined in claim 1, and R3 is as defined in claim 2. 14. The compound according to claim characterized in that y = 0 and x = 2. 15. The compound according to claim characterized in that it is of the general formula (III) wherein R, x, y, X, and Y are as defined in claim 1, and R3 is as defined in claim 2. 16. The compound according to claim 15, characterized in that y = 0 and x = 2. The compound according to claim 10, characterized in that it is of the general formula (IV) wherein P is of the formula (c), R1, x, y, X, and Y are as defined in claim 1, and R3 is as defined in claim 2, and wherein D, is a heteroaryl ring of five elements, the ring comprises one or two atoms selected from the group consisting of nitrogen, sulfur and oxygen; and when the heteroaryl ring comprises one or two nitrogen atoms, a R6 group is attached to any nitrogen atom that permits substitution. The compound according to claim 17, characterized in that D is a thiophene and P is attached to ring D. 19. The compound according to claim 17, characterized in that D is pyrrole and P is attached to the nitrogen atom in the ring D. 20. The compound according to claim 17, characterized by the fact that D is furan and P is attached to the ring D. 21. The compound according to claim 10, characterized in that it is of the general formula (V) wherein P is of the formula (c) as defined in claim 1, R1, x, y, X and Y, and R3 are as defined in claim 1, and wherein D is a five-membered heteroaryl ring , the heteroaryl ring comprises one or two atoms selected from the group consisting of nitrogen, sulfur and oxygen; and when the heteroaryl ring comprises one or two nitrogen atoms, a R6 group is attached to any nitrogen atom that permits substitution. 22. The compound according to claim 11 or 12 characterized in that it is of the general formula (V) wherein P is of the formula (a) or (b) as defined in claim 1, preferably wherein R2 is H, X, Y, and R3 are as defined in claim 1, and wherein D is a five-element heteroaryl ring, the heteroaryl ring comprises one or two atoms selected from the group consisting of nitrogen, sulfur and oxygen; and when the heteroaryl ring comprises one or two nitrogen atoms, a R6 group is attached to any nitrogen atom that permits substitution. 23. The compound according to any one of claims 11 and 12, characterized in that it is of the general formula (VI) wherein P is of the formula (a) or (b) as defined in claim 1, preferably wherein R2 is H, X and Y are as defined in claim 1, and R3 is as defined in the claim The compound according to any one of claims 11 and 12, characterized in that it is of the general formula (VII) wherein P is of the formula (a) or (b) as defined in claim 1, preferably wherein R2 is H, X and Y are as defined in claim 1, and ¾ is as defined in the claim 4. The compound according to any one of claims 11 and 12, characterized in that it is of the general formula (VIII) (vm) wherein P is of the formula (a) or (b) as defined in claim 1, preferably wherein R2 is H, X, Y, and R3 are as defined in claim 1. 26. The compliant compound with any one of claims 11 and 12, characterized in that it is of the general formula (IX) wherein R7 in the formula (IX) is: (a) H, (b) Ci-6-alkyl, (c) benzyl, (d) -CH2-CH2-OH, or (e) -CH2-CH2-0 -CH3 / y wherein P is of the formula (a) or (b) as defined in claim 1, preferably wherein R2 is Hr X, Y, and R3 are as defined in claim 1. 27.The compound according to claim 10, characterized in that it is of the general formula (X) wherein P is of the formula (a) or (b) as defined in claim 1, preferably wherein R2 is H, X, Y, and R3 are as defined in claim 1. 28. The compliant compound with the claim characterized in that it is of the general formula (XI) wherein P is of formula (a) or (b) as defined in claim 1, preferably wherein R2 is H, X and Y are as defined in claim 1, and R3 is as defined in claim 4. A compound according to any one of claims 1 to 12, characterized in that it is of the general formula (XII): or a pharmaceutically acceptable salt thereof, wherein P and R3 are attached to the same ring or rings different from rings A and B, wherein A, B, Y, P, and R3 are as defined in claim 1. The compound according to claim 13, characterized in that it is the compound 6-Benzenesulfonyl-4-piperazin-1-yl-quinoline hydrochloride; 6 - [(2-fluorophenyl) sulfonyl] -4-piperazin-1-yl-quinoline hydrochloride; 6- (1-naphthylsulfonyl) -4-piperazin-1-yl-quinoline hydrochloride; 6- [(3,4-Dichlorophenyl) sulfonyl] -4-piperazin-1-yl-quinoline hydrochloride; 6 - [(3,5-Dimethylphenyl) sulfonyl] -4-piperazin-1-yl-quinoline hydrochloride; 6- [(2-Chloro-6-methylphenyl) sulfonyl] -4-piperazin-1-yl-quinoline hydrochloride; 6- [(4-chlorophenyl) sulfonyl] -4-piperazin-1-yl-quinoline hydrochloride; 6- [(2-methyl, 4-tert-butylphenyl) sulfonyl] -4-piperazin-1-yl-quinoline hydrochloride; 6- [(3,4-Dimethylphenyl) sulfonyl] -4-piperazin-1-yl-quinoline hydrochloride; 6 - [(2, 3-Dichlorophenyl) sulfonyl] -4-piperazin-1-yl-quinoline hydrochloride; 6 - [(4-tert-Butylphenyl) sulfonyl] -4-piperazin-1-yl-quinoline hydrochloride; 6- [(4-isopropylphenyl) sulfonyl] -4-piperazin-1-yl-quinoline hydrochloride; (4-Piperazin-1-yl-6- { [4- (trifluoromethyl) phenyl] sulfonyl} quinoline hydrochloride; 6- [(4-tert-butylphenyl) sulfonyl] -4- (1, 4- diazepan-1-yl) quinoline; and 4- (1, 4-diazepan-1-yl) -6- [(4-isopropyl-phenyl) -sulfonyl] -quinoline, 31. The compound according to claim 15, characterized in that it is the compound 7- (2-chloro-6-methyl-benzenesulfonyl) -1-piperazin-1-yl-isoquinoline hydrochloride; 7- (2-t-butyl-benzenesulfonyl) -1-piperazin-1 hydrochloride - il-isoquinoline; 7- (3,4-dichlorobenzenesulfonyl) -1- piperazin-1-yl-isoquinoline hydrochloride; 7- (2,4-dimethylbenzenesulfonyl) -1-piperazin-1-yl hydrochloride - isoquinoline; 7- (2,5-dimethylbenzenesulfonyl) -1-piperazin-1-yl isoquinoline hydrochloride; 7- (p-chlorobenzenesulfonyl) -1-piperazin-1-yl isoquinoline hydrochloride; of 7-benzenesulfonyl-1- [1,4] diazepan-1-yl-isoquinoline; Hydrochloride of 7- (4- terb- utilbenzenesulfonyl) - 1- [1,4] diazepan-1-yl isoquinoline; 7- (2-Chloro-6-methyl-benzenesulfonyl) -1- [1,4] diazepan-1-yl-isoquinoline hydrochloride; 7- (3,5-dimethylbenzenesulfonyl) -1- [1,4] diazepan-1-yl isoquinoline hydrochloride; 7- (3,4-dichlorobenzenesulfonyl) -1- [1,4] diazepan-1-yl isoquinoline hydrochloride; 7- (4-chlorobenzenesulfonyl) -1- [1,4] diazepan-1-yl isoquinoline hydrochloride; 7- (3,4-dimethylbenzenesulfonyl) -1- [1,4] diazepan-1-yl isoquinoline hydrochloride; 7- (2-tert-Butyl-benzenesulfonyl) -1- [1,4-diazepane-1-yl-isoquinoline hydrochloride; 7- Benzenesulfonyl-1-piperazin-1-yl-isoquinoline hydrochloride; and 7- (4-tert-Butyl-benzenesulfonyl-1-piperazin-1-yl-isoquinoline) Hydrochloride 32. The compound according to claim 17, characterized in that it is the compound Hydrochloride of 4- (1, 4-diazepan-1-yl) -2- (phenylsulfonyl) thieno [3, 2-c] pyridine; 4- (1, 4-diazepan-1-yl) -2- [(3,4-dichlorophenyl) sulfonyl] thieno [3, 2-c] pyridine hydrochloride; 4- (1, 4-diazepan-1-yl) -2- [4-tert-butylphenylsulfonyl] thieno [3, 2-c] pyridine hydrochloride; 4- (1, 4-diazepan-1-yl) -2- [4-tert-butylphenylsulfonyl] thieno [3, 2-c] pyridine hydrochloride; 4- (1, 4-diazepan-1-yl) -2- [3, 4-dimethylphenylsulfonyl] thieno [3, 2-c] pyridine hydrochloride; 2- [(4-Bromophenyl) sulfonyl-] 4- (1-diazepan-1-yl) -thieno [3, 2-c] pyridine hydrochloride; 2- (Phenylsulfonyl) -4- piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 2- (3-methoxy-benzenesulfonyl) -4-piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 2- (4-methoxy-benzenesulfonyl) -4-piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 4- Piperazin-1-yl-2- hydrochloride. { [(4-trifluoromethyl) phenyl] sulfonyl} thieno [3, 2- c] pyridine; 2- [(2-tert-Butylphenyl) sulfonyl] -4-piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 2- [(3,4-Dichlorophenyl) sulfonyl] -4-piperazin-1-ylthieno [3r-c] pyridin-2-sulfonamide hydrochloride; 2- [(4-tert-Butylphenyl) sulfonyl] -4-piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 2- (1-Naphthylsulfonyl) -4- piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 2- [(3-fluorophenyl) sulfonyl] -4-piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 2- (Mesitylsulfonyl] -4- piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 2- [(2-methoxyphenyl) sulfonyl] -4-piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 2- [(2R-Dimethoxyphenyl) sulfonyl] -4-piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 2- [(2,4-Dimethylphenyl) sulfonyl] -4-piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 2- [(2,5-Dimethylphenyl) sulfonyl] -4-piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 2- [(2-ethylphenyl) sulfonyl] -4-piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 4- (Piperazinyl) -2- (3-methoxybenzyl-sulfonyl) -thienopyridine hydrochloride; 2- (Benzylsulfonyl) -4- piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 4- Piperazin-1-yl-2- hydrochloride. { [4- (trifluoromethyl) benzyl] sulfonyl} thieno [3,2-c] pyridine; [(3-bromobenzyl) sulfonyl] -4-piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 2- [(2, 3-difluorobenzyl) sulfonyl] -4- piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; [(4-bromobenzyl) sulfonyl] -4-piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 2- Hydrochloride. { [2,5-bis (trifluoromethyl) benzyl] sulfonyl} - 4- piperazin-1-ylthieno [3, 2-c] pyridine; 2- [(4-methylbenzyl) sulfonyl] -4-piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 2- Hydrochloride. { [5- Chloro-2- (trifluoromethyl) benzyl] sulfonyl} - 4- piperazin-1-ylthieno [3, 2-c] pyridine; 2- [(3,5-dimethoxybenzyl) sulfonyl] -4- piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 2- [(2-Naphthylmethyl) sulfonyl] -4-piperazin-1-ylthieno [3, 2-c] pyridine hydrochloride; 4- Piperazin-1-yl-2- hydrochloride. { [4- (1, 2, 3-thiadiazol-4-yl) benzyl] sulfonyl} thieno [3, 2-c] pyridine; 1- (4-pyrrolidin-1-ylphenyl) -2- [(4-piperazin-1-ylthieno [3,2-c] pyridin-2-yl) sulfonyl] ethanone hydrochloride; and 1- [4- (Diethylamino) phenyl] -2- [(4-piperazin-1-ylthieno [3, 2-c] pyridin-2-yl) sulfonyl] ethanone hydrochloride. 33. The compound in accordance with the claim 17, characterized in that it is the compound Chlorohydrate of 1- (4-methylphenylsulfonyl) -4-piperazin-1-yl-1H-pyrrolo [3, 2-c] pyridine; 1- (3-Chloro-2-methylphenylsulfonyl) -4- piperazin-1-yl-1H-pyrrolo [3, 2-c] pyridine hydrochloride; 1- (3,4-Dimethoxyphenylsulfonyl) -4-piperazin-1-yl-1H-pyrrolo [3, 2-c] pyridine hydrochloride; 4- (4-Piperazin-1-yl-pyrrolo [3, 2-c] pyridin-1-sulfonyl) -benzonitrile hydrochloride; 1- (4,5-dichlorothiophene-2-sulfonyl) -4- piperazin-1-yl-1H-pyrrolo [3, 2-c] pyridine hydrochloride; 1- (2-Chloro-4-fluorophenylsulfonyl) -4- piperazin-1-yl-1H-pyrrolo [3, 2-c] pyridine hydrochloride; 1- Phenylmethanesulfonyl-4-piperazin-1-yl-1H-pyrrolo [3, 2-c] pyridine hydrochloride; 1- (5-chloro-thiophene-2-sulfonyl) -4-piperazin-1-yl-1H-pyrrolo [3, 2-c] pyridine hydrochloride; 1- (4-Butyl-benzenesulfonyl) -4-piperazin-1-yl-1H-pyrrolo (3, 2-c) pyridine hydrochloride; 1- (4-phenoxy-benzenesulfonyl) -4-piperazin-1-hydrochloride il- 1H- pyrrolo (3, 2- c) pyridine; 1- (phenylsulfonyl) -4- piperazin-1-yl- 1H- pyrrolo [3, 2-c] pyridine hydrochloride; 1- (4- chlorophenyl) sulfonyl] -4-piperazin-1-yl-1H-pyrrolo [3, 2-c] pyridine; 1- [(4-methoxyphenyl) sulfonyl] -4-piperazin-1-yl-1H-pyrrolohydrochloride [ 3, 2- c] pyridine; 1- [(2-methoxy-5-methylphenyl) sulfonyl] -4- piperazin-1-yl-1H-pyrrolo [3, 2-c] pyridine hydrochloride; and 4-chlorohydrate piperazin-1-yl-1- {[[2- (trifluoromethyl) phenyl] sulfonyl} - 1H- pyrrolo [3, 2-c] pyridine 34. The compound according to claim 23, characterized in that it is the compound E- (4-methylphenyl) -4- (4-methylpiperazin-1-yl) thieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; p-tolylamide hydrochloride 2-bromo-4- ( 4-methyl-piperazin- 1- il) -thieno [3, 2-c] pyridine-3-sulfonic acid; 4- (4-methylpiperazin-1-yl) -n-phenylthieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; (3-Fluoro-5-trifluoromethyl-phenyl) -amide 4-piperazin-1-ylthieno [3, 2-c] pyridine-2-sulfonic acid hydrochloride; (4-Chloro-phenyl) -amide 4-piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonic acid hydrochloride; (4-isopropyl-phenyl) -amide 4-piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonic acid hydrochloride; P-Tolylamide 4-piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonic acid hydrochloride; 4- (4-methyl-piperazin-1-yl) -N- (2-cyclohex-1-en-1-ylethyl) -thieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; 2- (4- (4-methylpiperazin-1-yl) thieno [3, 2-c] pyridin-2-ylsulfonyl) -1,2,4,4-tetrahydroisoquinoline hydrochloride; 4- (4-methylpiperazin-1-yl) -N- (2-thien-2-ylethyl) thieno [3, 2-c] pyridin-2-sulphonamide hydrochloride; 4- (4-methylpiperazin-1-yl) -N- [1- (1-naphthyl) ethyl] thieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; 4- (4-methylpiperazin-1-yl) -N- (4-hexylphenyl) thieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; N- (3-chlorobenzyl) -4- (4-methylpiperazin-1-yl) thieno [3, 2-c] pyridin-2-sulfonamide; 4- (4-methylpiperazin-1-yl) -N- [1- (4-fluorophenyl) ethyl] thieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; N- (2, 3-difluorobenzyl) -4- (4-methylpiperazin-1-yl) thieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; 4- (4-methylpiperazin-1-yl) -N- (4-chloro-2,5-dimethoxyphenyl) thieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; 2-Bromo-4- (4-methyl-piperazin-1-yl) -N- (2-cyclohex-1-en-1-ylethyl) -thieno [3, 2-c] pyridin-3-sulfonamide hydrochloride; 2-Bromo-4- (4-methyl-piperazin-1-yl) -N- [(1S) -1- (2-naphthyl) -ethyl] -thieno [3, 2-c] pyridine-3-sulfonamide hydrochloride; 2-Bromo-4- (4-methyl-piperazin-1-yl) -N- [1- (4-fluorophenyl) -ethyl] -thieno [3, 2-c] pyridin-3-sulfonamide hydrochloride; 2- Bromo-4- (4-methylpiperazin-1-yl) -N- (2,4-, 5-trimethoxyphenyl) thieno [37-2 c] pyridin-3-sulfonamide; N- (3,4-dichlorophenyl) -4- piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; N- (2, 4-difluorophenyl) -4-piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; 4- Piperazin-1-yl- N- [3- (trilumphoromethyl) phenyl] thieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; N- (3-ethylphenyl) -4- piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; N- (3,4-dimethoxyphenyl) -4-piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; N- (4-bromo-2-methylphenyl) -4-piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; 2- (4-piperazin-1-ylthieno [3,2- c] pyridin-2-sulfonyl) -1,2,3-tetrahydro-isoquinoline hydrochloride; (2-thiophene-2-yl-ethyl) -amide 4-piperazin-1-ylthieno [3, 2-c] pyridin-2-sulphonic acid hydrochloride- (4-chloro-2, 5-hydrochloride) dimethoxy-phenyl) -amide 4-piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonic acid; Chlorohydrate of phenethylamide 4-piperazin-1-ylthieno [3, 2-c] pyridin-2-sulphonic acid hydrochloride; (2,6-diethyl-phenyl) -amide 4-piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonic acid hydrochloride; (3-phenylpropyl) -amide 4-piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonic acid hydrochloride; (3, 3-Diphenyl-propyl) -amide 4-piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonic acid hydrochloride; [2- (5-Methoxy-1H-indol-3-yl) -ethyl] -amide 4- piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonic acid hydrochloride; 4-Trifluoromethyl-benzylamide acid hydrochloride 4- piperazin-1-ylthieno [3,2-c] pyridin-2-sulfonic acid; Hydrochloride of benzyl ethyl amide 4- piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonic acid; N- (3-ethylphenyl) -4- piperazin-1-ylthieno [3, 2-c] pyridin-3-sulfonamide hydrochloride; N- (4-isopropylphenyl) -4- piperazin-1-ylthieno [3, 2-c] pyridin-3-sulfonamide hydrochloride; N- (4-methylphenyl) -4- (pyrrolidin-3-yloxy) thieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; N- (4-methylphenyl) -4- (pyrrolidin-3-yloxy) thieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; N- (4-methylphenyl) -4- (piperidin-4-yloxy) thieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; N- (2, 3-difluorobenzyl) -4-piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; N- (3-chlorobenzyl) -4- piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonamide hydrochloride; Phenylamide 4-piperazin-1-yl-thieno [3, 2-c] pyridin-2-sulfonic acid hydrochloride; (4- tert-butylphenyl) -amide acid hydrochloride 4- piperazin-1-ylthieno [3, 2-c] pyridin-2-sulfonic acid; Phenylamide acid hydrochloride 4- (4-methyl-piperazin-1-yl) -thieno [3,2-c] pyridin-2-sulphonic acid; (3-chloro-phenyl) -amide 4- (4-methyl-piperazin-1-yl) -thieno [3, 2-c] pyridin-2-sulfonic acid hydrochloride; Phenylamide 2-bromo-4- (4-methyl-piperazin-1-yl) -thieno [3, 2-c] pyridin-3-sulfonic acid hydrochloride; 4- (4-Methyl-piperazin-1-yl) -thieno [3, 2-c] pyridine-3-sulfonic acid hydrochloride (4-methylphenyl) -amide; N-Phenyl-7- piperazin-1-ylthieno [2, 3-c] pyridin-2-sulfonamide hydrochloride. 35. A compound in accordance with the claim 25, characterized in that it is the compound N- (4-methylphenyl) -4- piperazin-1-ylfuro [3, 2-c] pyridin-2-sulfonamide hydrochloride; N-phenyl-4-piperazin-1-ylfuro [3, 2-c] pyridin-2-sulfonamide hydrochloride; and N-phenyl-7-piperazin-1-ylfuro [2, 3-c] pyridin-2-sulfonamide hydrochloride. 36. Un. compound in accordance with the claim 25, characterized in that it is the compound phenylamide 4-piperazin-1-yl-thiazolo [4,5- c] pyridin-2-sulfonic acid hydrochloride. 37. A compound in accordance with the claim 26, characterized in that it is the compound N- (4-methylphenyl) -4- piperazin-1-yl-1H-pyrrolo [3, 2-c] pyridin-2-sulfonamide hydrochloride; N-phenyl-4-piperazin-1-yl-1H-pyrrolo [3, 2-c] pyridin-2-sulfonamide hydrochloride; and N-phenyl-7- piperazin-1-yl-1H-pyrrolo [2, 3-c] pyridin-2-sulfonamide hydrochloride. 38. A compound in accordance with the claim 27, characterized in that it is the compound 4-chloro-N- [4- (pyrrolidin-3-yloxy) -1-naphthyl] benzenesulfonamide hydrochloride; 4-methoxy-N- [4- (pyrrolidin-3-yloxy) -1-naphthyl] -benzenesulfonamide hydrochloride; 5- Chloro- N- [4- (pyrrolidin-3-yloxy) -1-naphthyl] thiophene-2-sulfonamide hydrochloride; 4- Chloro-N- [4- (piperidin-3-yloxy) -1-naphthyl] benzenesulfonamide hydrochloride; 4- Methoxy-N- [4-piperidin-3-yloxy) -1-naphthyl] benzenesulfonamide hydrochloride; 5- Fluoro-2-methyl-N- [4- (piperidin-4-yloxy) -1-naphthyl] benzenesulfonamide hydrochloride; 5- Chloro-N- [4- (piperidin-4-yloxy) -1-naphthyl] thiophene-2-sulfonamide hydrochloride; 4- Chloro-N- hydrochloride. { 4- [(3S) -pyrrolidin-3-yloxy] -1- naphthyl) benzenesulfonamide; and 4-Chloro-N- Hydrochloride. { 4- [(3R) -pyrrolidin-3-yloxy] -1- naphthyl) benzenesulfonamide. 39. A process for the preparation of a compound according to any one of claims 1 to 38, the method is characterized in that it comprises the steps of: (a) Mitsonobu reaction of 4-nitro-1-naphthol with 3-hydroxypyrrolidine protected with Boc or 4-hydroxypiperidine; (b) reduction of the nitro group in the nitronaphthalene obtained in step (a) to form an aminonaphthalene derivative; and (c) synthesis of a sulfonamide by reaction of the aminonaphthalene obtained in step (b) with a suitable sulfonyl chloride. 40. A process for the preparation of a compound according to claim 10, characterized in that R1 p is Or said method comprises the steps of: preparation of the 5-membered heteroaromatic ring fused with pyridine substituted with halogen, reduction of an aromatic nitro group; aromatic nucleophilic substitution with a thiol via an intermediate diazo; oxidation of the thiol derivative to a sulfone; introduction of a halogen atom by electrophilic aromatic substitution; aromatic nucleophilic substitution of the halogen with a diamine. 41. A process for the preparation of a compound according to claim 10, characterized in that of: preparation of the pyridine fused with the 5-membered heteroaromatic ring; introduction of a carboxylic portion; conversion of the carboxyl portion to amine by the rearrangement of Curtius; the reaction of the amine group with a sulfonyl chloride. 42. A process for the preparation of a compound, according to claim 11, characterized in that P is said method comprises the steps of: preparing the 5-membered heteroaromatic ring fused with pyridine; introduction of the sulfonyl chloride portion by nucleophilic addition; reaction of the sulfonyl chloride portion with an aniline to a sulfonamide obtained; aromatic nucleophilic substitution of chlorine with a diamine. 43. A compound according to any one of claims 1 to 38, for use in therapy. 44. A compound according to any one of claims 1 to 38 and for the case when ring A and B are both phenyl, P is any one of formula (a) or (c) substituted in position 7 on the naphthalene ring , and R3 is substituted in position 1 on the naphthalene ring, for use in the treatment or prophylaxis of a disorder related to the 5-HT6 receptor, such as obesity, type II diabetes, and / or central nervous system disorders, to achieve the reduction of body weight and weight gain. 45. A compound according to any one of claims 1 to 38 for use in the treatment or prophylaxis of disorders of the central nervous system. 46. A compound according to any one of claims 1 to 38, for the case when ring A and B are both phenyl, P is any one of formula (a) or (c) substituted in position 7 on the naphthalene ring, and R3 is substituted in position 1 on the naphthalene ring, and for the case when ring D is a pyrrole ring, P is of the formula (c) and R3 is of the formula substituted in position 3 on the pyrrole ring, for use in the treatment or prophylaxis of type II diabetes. 47. A compound according to any one of claims 1 to 38, and for the case when the ring D is a pyrrole ring, P is of the formula (c) and R3 is of the formula substituted in position 3 on the pyrrole ring, for use in the treatment or prophylaxis of obesity, to achieve the reduction of body weight and the gain of body weight. 48. A pharmaceutical formulation characterized by a comprises a compound according to any one of claims 1 to 38 as an active ingredient, in combination with a pharmaceutically acceptable diluent or carrier. 49. A pharmaceutical formulation characterized in that it comprises a compound according to any one of claims 1 to 38, and for the case when ring A and B are both phenyl, P is any one of formula (a) or (c) substituted in position 7 on the naphthalene ring, and R3 is substituted in position 1 on the naphthalene ring, as an active ingredient, for use in the treatment or prophylaxis of a disorder related to the 5-HT6 receptor, such as obesity, diabetes, Type II, and / or disorders of the central nervous system, to achieve the reduction of body weight and weight gain. 50. A pharmaceutical composition characterized in that it comprises a compound according to any one of claims 1 to 38 as an active ingredient, for use in the treatment or prophylaxis of disorders of the central nervous system. 51. A pharmaceutical formulation characterized in that it comprises a compound according to any one of claims 1 to 38, for the case when ring A and B are both phenyl, P is any one of formula (a) or (c) substituted in position 7 on the naphthalene ring, and R3 is substituted in position 1 on the naphthalene ring, and for the case when ring D is a pyrrole ring, P is of the formula (c) and R3 is of the formula substituted in position 3 on the pyrrole ring, as an active ingredient for use in the treatment or prophylaxis of type II diabetes. 52. A pharmaceutical formulation characterized in that it comprises a compound according to any one of claims 1 to 38, and for the case when ring D is a pyrrole ring, P is of formula (c) and R3 is of the formula substituted in position 3 on the pyrrole ring, as an active ingredient for use in the treatment or prophylaxis of obesity, to achieve the reduction of body weight and the gain of body weight. 53. A method for the treatment or prophylaxis of a disorder related to the 5-HT6 receptor, such as obesity, type II diabetes, and / or central nervous system disorders, to achieve the reduction of body weight or gain. of body weight, characterized in that it comprises administering to a subject in need of said treatment an effective amount of a compound according to any one of claims 1 to 38, and for the case when the rings A and B are both phenyl, P is any one of formula (a) or (c) substituted in position 7 on the naphthalene ring and R3 is substituted in position 1 on the naphthalene ring. A method for the treatment or prophylaxis of disorders of the central nervous system, characterized in that it comprises administering to a subject in need of said treatment an effective amount of a compound according to any one of claims 1 to 38. 55. A method for the treatment or prophylaxis of type II diabetes, characterized in that it comprises administering to a subject in need of said treatment an effective amount of a compound according to claims 1 to 38, for the case when ring A and B are both phenyl , P is any one of formula (a) or (c) substituted in position 7 on the naphthalene ring, and R3 is substituted in position 1 on the naphthalene ring, and for the case when ring D is a pyrrole ring, P is of the formula (c) and 3 is of the formula substituted in position 3 on the pyrrole ring. 56. A method for the treatment or prophylaxis of obesity and to achieve the reduction of body weight and body weight gain, characterized in that it comprises administering to a subject in need of said treatment an effective amount of a compound in accordance with any one of of claims 1 to 38, and for the case when the ring D is a pyrrole ring, P is of the formula (c) and R3 is of the formula substituted in position 3 on the pyrrole ring. 57. A method for modulating the activity of the 5-HT6 receptor, characterized in that it comprises administering to a subject in need thereof an amount of a compound according to any one of claims 1-38. 58. Use of a compound according to any one of claims 1 to 38, for the case when ring A and B are both phenyl, P is any one of formula (a) or (c) substituted in position 7 on the naphthalene ring, and R3 is substituted in position 1 on the naphthalene ring, for the manufacture of a medicament, for use in the treatment or prophylaxis of a disorder related to the 5-HT6 receptor, such as obesity, type II diabetes, and / or disorders of the central nervous system, to achieve the reduction of body weight and weight gain. 59. Use of a compound according to any one of claims 1 to 38 for the manufacture of a medicament for use in the treatment or prophylaxis of disorders of the central nervous system. 60. Use of a compound according to any one of claims 1 to 38, for the case when ring A and B are both phenyl, P is any one of formula (a) or (c) substituted in position 7 on the naphthalene ring, and R3 is substituted in position 1 on the naphthalene ring, and for the case when ring D is a pyrrole ring, P is of the formula (c) and R3 is of the formula substituted in position 3 on the pyrrole ring, for the manufacture of a medicament for use in the treatment or prophylaxis of type II diabetes. 61. Use of a compound according to any one of claims 1 to 38, for the case when the ring D is a pyrrole ring, P is of the formula (c) and R3 is of the formula substituted in position 3 on the pyrrole ring for the manufacture of a medicament for use in the treatment or prophylaxis of obesity, to achieve 1 reduction of body weight and body weight gain.