SA02230148B1 - Benzimidazoles are useful in treating sexual dysfunction - Google Patents

Abstract

Abstract: The present invention relates to the use of compounds of formula (I) to treat sexual dysfunction and compositions containing compounds of formula (I) to treat sexual dysfunction.

Description

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Useful in the treatment of benzimidazoles sexual dysfunction Full description Background of the invention benzimidazoles The present invention relates to the use of sexual imidazoles and compositions containing these compounds to treat sexual dysfunction Role in dopamine (DA) Preclinical evidence suggests that dopamine may initiate sexual arousal via the arrival of mammals in mammals penile erection. And the cerebral cortex has sensory information (related to sexual desire) to the cerebral cortex, in addition to the amygdala of the cerebellum, he the brain, extended neural connections with limbic structures, periaqueductal gray, such as the gray matter surrounding the ducts midbrain, the structures of the midbrain There are two important nuclei in the hypothalamus, the hypothalamus and the hypothalamus (PAG) | 0 and the nucleus next to (MPOA) medial preoptic area the area of the medial anterior optic lobes and 0137 plays an important role in MPOA and the two nuclei play. paraventrioular nucleus (PVN) Sexual behavior Since diffuse lesions on both sides of these two regions completely limit sexual behavior in males. The hypothalamic excitatory dopaminergic pathway is coupled to the MPOA 5 PVN nerves supplying the incerto-hypothalamic dopaminergic pathway 0, which promotes erection. Systemic administration of DA agonists facilitates the effect of (R11) apomorphine Jie DA receptor agonists DA receptor (6aR) Lloyd-11 » 01-nilonic [eed benzo [D SHES] Jae sue /a-quaternary quinpirole «(5,6,6a,7-tetrahydro-6-methyl-4H-dibenzo[de,g]quinoline-10,1 1-0101 (5) 3- (3-hydroxyphenyl) N-(-) 7-(“-hydroxyphenyl)-11-propylpiperidine

YAYA v (3-PPP) penile erection in aad which is an effect inhibited by haloperidol which is a central line DA antagonist and since the erectile effect cannot be inhibited by domperidone which is It is a peripheral DA antagonist. A peripheral cantagonist, it is believed that the erection-promoting effect of DA precursors occurs centrally (see ref. Andersson K and Wagner G, Physiology of penile erection, Physiol (Rev (1995) 75: 191-236 and deGroat W and Booth A, Neural Control of Penile Erection, in: Nervous control of urogenital system, Vol. 3, (ed. Maggi, C) ( 1993) p. Hardwood Academic Publishers, Chur, Switzerland, 467-524; ref. Moreland RB, Nakane M, Hsich G and Brioni JD, Prospectives for Pharmacotherapy of Male Erectile (Dysfunction, Curr Opinion CPNS Invest Drugs (2000) 2:283-302) \ (the CNS nervous system in the DA and clinical examination data also show that CNS

Onn plays a role in regulating sexual behavior in males as (central nervous system) hydroxyphenylalanine (SU) Ledopa from the sexual stimulant effect of compound 1-Dopa and from the effect of Parkinson in patients with Parkinson's disease (dihydroxyphenylalanine

Morales A, Erection Enhancement of Apomorphine 76 in Humans (See reference Veo

Geaton J, Johnston B and Adams M, Oral and Topical Treatment of Erectile Dysfunction: ¢present and future, in: Urologic Clinics of North America, (1995) Vol. 22, p. 879-886

Padma-Nathan H, Auerbach S, Lewis R, Lewand M and Perdok R , Efficacy and safety of apomorphine SL vs. placebo for male erectile dysfunction (MED), Urology (1999)

Dula E, Keating W, Siami P, Edmonds A, 161:214; And what was stated in the reference (abstract 821) Y.

O'Neil J, Efficacy and safety of fixed-dose and dose-optimization regimens of sublingual apomorphine versus placebo in men with erectile dysfunction, Urology (2000) 56:130-135 Protein receptors vs. send a signal across the cell membrane by coupling with intracellular GTP-binding proteins YAYA

¢ Several 6 proteins (including Gs and 6 Gis) have been identified as triggering specific events within the cell (see ref. Milligan G and Rees S, Chimaeric 6 proteins: their (potential use in drug discovery, Trends Pharmacol Sci (1999) 20:118-124 There are five known DA receptors that are classified into two groups: Jali-like and Jali-like receptors, Dy-like receptors Ds 3 Dy receptors Dy-like receptors include Ds s Ds “Dy” (BUX) receptors (Missale C, Nash Robinson S, Jaber M and Caron M, Dopamine receptors: from structure to function, 5, ref. Physiol Rev (1998) 78:189-225 Dy-like receptor classmates are Gs-coupled — they can activate adenylate cyclase Dy-like class 01 receptors are Gs-coupled It works to increase the level of calcium (Jala calcium) in the cell and activates adenylate cyclase 1. The members of the 0-like family are receptors coupled with 6, which can activate adenylate cyclase, and the Dy receptor is considered The most abundant and extensive DA receptor generated in the ONS was demonstrated by expression of mRNA (messenger ribonucleic acid) and by immunohistochemical studies. Vallone D, Picetti R and Borreli E, Structure and function of dopamine receptors, Neurosci Biobehav Rev (2000) 24:125-132 (located in the striatum cstriatum nucleus accumbens dc gana) nucleus accumbens of al cells between the appendix nucleus and the anterior perforata substance) and the olfactory tubercle (Ye) in addition to the limbic system (climbic system) under the hypothalamus and thalamus. Expression of the Dy receptor in heart and kidney; Although the function of these peripheral Dy receptors has been clarified; It has proven its role in controlling hemodynamic variables. The 0 receptor, although it has a greater affinity for DA than for the Dy receptor, is sparsely distributed in the ONS with no evidence of expression outside the CNS—members of the Dy-like superfamily are Dy-coupled receptors. Gy accepts adenylate cyclase and works to increase calcium levels within the body's metabolism.

cell. The Dy receptor is the most abundant of the Dy-like receptors and is found in the brain regions Jia, striatum and substantia nigra, and in peripheral regions such as the heart, pituitary gland and kidney, and there is a Dy receptor. Dy abundantly in the Calla Islands, with clear cluster clusters in the regions of the ventral striatum (s) / ventral striatum °) 3 accompanis » olfactory tubercle; The dentate gyrus (dendate gyrus and striated cortex ai) Schwartz J and Sedwall G, Ds § Suzuki M, Hurd Y, Sokoloff (dopamine receptor mRNA is widely expressed in human brain, Brain Res ( 1998,779,58-74 Expression of the 01 receptor has been demonstrated by 3218 in situ hybridization and documented immunohistochemical studies.More recently, studies have shown that expression of 01 receptor is highest in the entorhinal cortex. “entorhinal cortex the lateral separating nucleus ¢septal nucleus of the hippocampus and the medial anterior optic lobe area (MPOA) of the hypothalamus hil) according to the references Primus R, Thurkauf A, Xu J , Yevich E, Mecinerney S, Shaw K, Tallman J and Gallagher D, Localization and characterization of binding sites in rat and human brain by use of the novel Dy receptor-selective dopamine ligand 0. ['HINGD 94-1, J Pharmacol Exp Ther (1 997) 282: 1020-1027 1 The localization of Ds differs from the distribution of (BD; brain where Dy receptors are most abundant in striatal regions. Expression is Considering the role of the hypothalamus as a region of integration between the cortex and spinal pathways, the contribution of Dy receptors in the is AY CNS regions of the thalamus cannot be excluded. Y. hypothalamic and spinal. The US patent, VEVYACE, in Sterling's name, reveals benzimidazole compounds useful as tranquilizers, tranquilizers, analgesics. skeletal muscle relaxants ida agents for adrenaline cadrenolytic agents dia 7 8a agents for temperatures chypothermic agents yo antispasmodics canti-convulsants agents for lowering blood pressure chypotensive agents .cardiovascular agents and cardiovascular agents

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. Sule and co-workers reveal benzimidazole compounds bearing a substituted at the © (1) 7-(101-piperazinyl) substituent at (2-(N4-substituted N1-piperazinyl)methyl-5-(or) (N4). 6)-substituted benzimidazoles as having anthelmintic activity. 2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1H- benzimidazole although the compound was not considered an anthelmintic by Yad. See Bull.Haffkine Inst., 1978. 6(2),62-64 OVAYVIA US Patent Merck Sharp and Dome disclose 5-benzene imidazoles 6020108201 as D,1 antagonists and beneficial antipsychotic agents. antipsychotic agents US Patent No. 148494/09 Merck Sharp and Dom describe benzimidazole compounds as D, ligands Dy for disorders of the dopamine system, including schizophrenia. schizophrenia depression depression ¢nausca Parkinson's disease ve bradykinesia ctardive dyskinesia Disorders of hypothalamic-pituitary function disorders of the upper alimentary canal Gastrointestinal drug abuse disorders Psychotic disorders In addition to cardiovascular disorders The present invention specifies a therapeutic use of benzimidazoles xe in formula (I) in the treatment of sexual dysfunction in mammals . Specifically, these compounds are useful in treating sexual dysfunction; including; but not limited to » male erectile dysfunction (MED). General Description of the Invention The present invention relates to a method for treating sexual dysfunction of the breasts; especially ve human beings; It includes giving the aforementioned mammal a therapeutically effective amount of a compound of formula (1) taken as v.

A

Ra 27 and N N J > ——

DASA

SZ

R¢N

Ry, TE (1) where: acceptable Jana 42a prodrug or prodrug amide cester amide or salt; Esther from: Jet A

Raz

Re Ra Ra Ra Ry Ry

Ry J BY Loa 8 R I

J Arts Life

Y.A. Rj m m bs == Ra 01 7 R a a n s ¢ 2 7 3 ' 0 ¢ ASN Rs ¢ x 'N Re ' Rs °

Raz R4 Ra R 1 R,

R i a Ra 8 . b x Ly X Ly As SI 8 Spa NY b * virgin 0 < AN N 3 Rs ¢ x N 3 6 Ry < Rs

R4 m Ra / x xx R 1 and 3 X —N . No ==

Th rh with tenderness for the ' B N ¢ Turk B ' BS N 3 ¢ Rs Rs ' A N Sia 8 R \ Shabak L OY L ALL N . Mn x / 7

SSA TRRC Re TT or 5;O NH from BS “0X ¢“CH,CH,CH,CH, or CH,CH,CH, “CH,CH, “CH, from oa L A hydrogen each separately from hydrogen JS CRs and Re Ry Ry (Ry

J calkylsulfinyl alkyl retinyl calkyl alkyl calkenyl alkenyl calkoxy alkoxy alkoxycarbonyl “alkynyl alkylthio” alkyl shi calkylsulfonyl captonyl calkylcarbonyloxy alkyl carbonyl <alkylcarbonyl alkyl carbonyl calkoxycarbonyl h

A

alkoxy la chalogen halogen “formyl cyano cyano carboxy hydroxyalkyl JX <hydroxy chaloalky! The chaloalkoxy haloalkyl or (NZ,Zy)carbonyl (NZ,Z,) carbonyl “NZ Z,” nitro mercapto mercapto each separately from group consisting of 2: 7 ash where (NZ Zy)sulfonyl (NZ\Z,) J calkylcarbonyl alkyl carbonyl calkyl alkyl hydrogen ° formyl formyl alkylsulfonyl hydrogen and M8 each of which is chosen on H adenoma Re Mal Ra alkyl sulfonyl calkylsulfinyl alkyl sulfonyl alkyl calkenyl alkoxy calkoxycarbonyl alkoxycarboxyl calkylthio 5 alkyl calkylsulfonyl ccarboxy carboxy calkylcarbonyloxy alkyl carbonyloxy calkylcarbonyl carbonyl Jl 01 chaloalkoxy halo alkoxy halogen formyl cyano cyano cmercapto mercapto hydroxyalkyl hydroxy hydroxy chaloatkyl (NZ. Zy)carbonyl ( NZ,Z,) or carbonyl 2NZ,Z, «nitro 5 alkyl carbonyl (kisi S alkoxy hydrogen of SBA Re carylcarbonyl aryl carbonyl calkylcarbonyl alkyl carbonyl calkyl Vo Or a carbonyl with a heterocyclecarbonyl heterocyclic carbonyl ring “cycloalkylcarbonyl ¢(NZ,Z;)carbonyl calkyl and the alkyl hydrogen is chosen from the hydrogens of Rs

SCH or CON of SBA" 2 and not present when the carbon bond == present when 2 carbon atoms are weighed 7 .CH or nitrogen represents 7 nitrogen atom Detailed description of the invention I have denied all Patents, patent applications and reference publications.In this specification in its entirety for reference.

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The present invention relates according to its principal embodiment to a method for the treatment of sexual dysfunction in Ndiye »in particular in humans; Include giving the aforementioned a therapeutic amount of a compound. 0 is in the form A Ra©

Ra > N N

Rg EE (1) o or a pharmaceutically acceptable prodrug thereof where: amide is a cester amide or salt; Esther: tar from. 2 3 A

Ra 8 Ra rR, Re 7 fz 2 Ry SC 1 if \ A Ry Ry. SN Rs

B dng Re NT (NY

TN-. 2 ¢ 5 7 B 6 0 0 ANT Re ¢ A 'N Re ¢ Rg

Rj Ry R R R,

R 1 a m Ra x —\__0O

X > Xx 8 Package sz

Tr PR NY jay R: © ¢ 2 N 3, Rs | x N 3 Rs 1 Rs

Ris x Sar: R

R, Ra | 1 - 3 R 2 —X EN 3 N } 1 sb I N ja i love door no = ¢ x N ¢ x; SN ¢ 2 N Fs ¢ Rs + Rg ¢ hs N 1 Sir R a Shep Shell ET Lyr O . d X i ¢ x N or ANN < bh SN ¢ Rg 4 for Rs (SJ 0 NH of 5a "2X ¢CH,CH,CH,CH, sl CH,CH,CH, «CH ,CH, he chooses from Yale

01 hydrogen each separately from hydrogen Sia To and Yaba Ry Ry but Baal

Ji calkylsulfinyl alkyl catkenyl calkoxy alkoxy alkylthio alkylsulfonyl calkylcarbonyloxy alkyl carbonyl calkylcarbonyl alkoxycarbonyl halo alkoxy 'halogen formyl 'cyano carboxy carboxy > hydroxyalkyl chaloalkyl chaloalkoxy (NZ Zy)carbonyl or carbonyl d'an '212: 22 “nitro enro” mercapto calkyl alkyl hydrogen 7 and 70 are selected separately from the group consisting of formyl hydrogen or formyl alkylsulfonyl calkylcarbonyl chydrogen And what each of them chooses separately from hydrogen Re makl Ra Ve alkyl sulfonyl calkylsulfinyl sulfurinyl Jf alkyl Jf alkenyl alkenyl calkoxy “alkoxycarbonyl J— 9: S alkoxy calkynyl alkynyl calkylthio alkyl feu calkylsulfonyl “carboxy calkylcarbonyloxy alkyl carbonyloxy calkylearbonyl carbonyl Jf halo alkyl chaloatkoxy halo alkoxy chalogen halogen formyl cyano-formel cmercapto marquette ¢hydroxyalky! Ji hydroxy chaloalkyl Ve (NZ, Z;)carbonyl (NZ,Z,) or carbonyl -NZyZy nitro alkoxycarbonyl chydrogen of hydrogen oust Rg

Je S alkyl carylcarbonyl calkylcarbonyl alkyl carbonyl (NZ.2,) or carbonyl heterocyclecarbonyl heterocycle carbonyl “cycloalkylcarbonyl ¢(NZ,Z;)carbonyl A talkyl or alkyl hydrogen [BLE +

SCH or CON selected from 7 and not present when carbon bond == present when 7 represents a carbon atom .CH or nitrogen represents 7 nitrogen and in another embodiment; The present invention relates to a method for treating sexual dysfunction in re

Ry breasts involves giving the said breast a therapeutically effective amount of a compound of formula (1); Where

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11

Rg 'halogen or hydrogen halogen separately from SBS TO hydrogen and M Re Rp

LSA 5Ls represents 8; bond ---- does not exist; Z thydrogen represents hydrogen (1) by convention in the formula and in another embodiment; The present invention relates to a method for the treatment of sexual dysfunction in “Ra Cus ¢ (1) from a compound of the formula Ladle said effective amount sa c lac) Dabe ¢ comprising °

Rg thalogen or halogen hydrogen each separately from hydrogen ous Rp and cyclized Re represents A bond ——— does not exist; oN represents Z hydrogen represents hydrogen and Sand “Ra (1) is defined in the formula LS Ry and Ry (Ry Ry (Ry) ; and Rs and in another embodiment the present invention relates to a method for the treatment of sexual dysfunction in (Rp dua (1) from a compound of the formula Ladle includes giving the aforementioned Diy an effective amount (od 1 and Rg thalogen or hydrogen halogen each separately from hydrogen Jia TS and what Re mal 8; bond ---- other than Z CH, representing L hydrogen, both of which have hydrogen Ry present; representing A

Ra

R 1 and welcomed

YT

Rs and pau thydrogen each represent Ry hydrogen; J »butt and Rs yo (1) as they were known in formula (0) of a compound with the formula Ladle in my literature, which includes giving the aforementioned a high amount of

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1" or halogen hydrogen from tas hydrogen on JS with select 5 Re "Rg Ry where ON Jia Z ¢CHy, L represents hydrogen of which hydrogen feder JS represents Rp or Rg ¢halogen representing A not present; TTT bond M R 1 mahlab R 3 bo x ~~ ~R4 and thydrogen each separately representing hydrogen Rs and Ry Ro “Ry Rs (1) is defined in the formula LER, © and in another embodiment the present invention relates to a method for treating sexual dysfunction in a compound of formula (0); where Ladle breasts comprises the administration of said dew by Active R or halogen hydrogen separately selected from hydrogen Rp and non-existent Re “Rp Ra TTT representing ?8; bond 2 hydrogen ; hydrogen | “ay Rg ; 10 Lm represents 00 b b ~ 1 (0) in the formula Capa and is as Ry Rp Ry as x “N Ry” or hydrogen halogen and with each separately selected Of hydrogen Re what “Ra where (N represents 7 CH, represents L hydrogen each separately represents hydrogen Re and Re thalogen Ve represents A does not exist;? TTT Association

VY

Ra

L.L

. 1: 1 x N Rs and 8 as thydrogen and Ba each represents hydrogen Rs Ry ; . (1) defined in the formulation and in another embodiment the present invention relates to a method for treating sexual dysfunction (1) from a compound of the formula Ladle JL xd r daa in breasts involving the administration of the said breast as ?; 7 ¢CH; L represents hydrogen of which K represents Re and Rp Re Rp where Kl ° represents A The bond ———— does not exist;

R2 duck > Rj - 'hydrogen yama and b having each of its hydrogen components RyRy; and x N 4 The present invention relates to a method for treating sexual dysfunction al and in the embodiment of hydrogen or halogen and with on A unit of hydrogen Re Rp Ry where each chooses 0 represents 7 ¢CH, represents L ' alkyl represents alkyl Rp hydrogen represents Rg hydrogen ; 00 8; bond ———— does not exist; m thql and t > pt 1 and a t as is thydrogen each representing hydrogens Re and Ry (Ry 4); the present invention relates to a method for the treatment of sexual dysfunction aT And in the embodiment of Ve (1) a therapeutic form of a compound with a dye a in Tddi we include giving 3 aforementioned mammalian amounts or hydrogen halogens each separately from JUS ZS hydrogen and m Re Rp Ry where alkyl where alkyl represents alkyl Re thydrogen represents hydrogen Rp thalogen

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Ve bond ———— does not exist; IN represents Z CH, Jha L methyl mentioned is a methylation represents A and - . NT TR hydrogen each represents hydrogen Rs and Ry «Ry Ry ; And, in another embodiment; The present invention relates to a method for the treatment of sexual dysfunction (1) mentioned as a therapeutic amount of a compound of the formula ol p Lac in an arrangement containing ° or hydrogen halogen separately from JS Chectar Rp H and “Ry Ra where Al lg aga is not TTT the bond oN represents 2 ¢ hydrogen transporting hydrogen Rg ¢ halogen

Ra

L

: yum "by either 8 hydrogen separately from hydrogen (JS) and subsequently choose Ry (Ry Ry ; (1) and .1 as defined by the formula hydroxy or hydroxy 0 The present invention 2 relates to a method for the treatment of sexual dysfunction 0 al and in embodiment (1) therapeutically from a compound of the formula Jad in a procedure involving the administration of the said Diy or hydrogen halogen separately from J selected Rp and Re «Rp represent dus oN JL fay 7 «CH, represent L thydrogen each represents hydrogen Rp and Rg thalogen do not exist; TTT Aad Hl 'eo

J A

Ra; . i 0 hy | NE Ra transforms Ry and hydrogen hydrogen Lge JS represents Ry and Ry (Ry ? -hydroxy YAYA

Vo And in another embodiment; The present invention relates to a method for treating sexual dysfunction (1) of a compound of formula Ladle in breasts comprising administration to said breast of an active dose or halogen each of JETS Rp and Re Re (Ry) where A does not exist; ---- dad HIN represents Z hydrogen represents hydrogen Rg ¢halogen

Ra L (1) PK and P as defined by Formula Ro Lost ONT M The present invention relates to a method for the treatment of sexual dysfunction AT and in an embodiment (1) of a compound of formula Ladle in Mammals It includes giving the aforementioned mammal an amount of Fal or halogen hydrogen separately from hydrogen JS JESS and with Re (Ra Ra where . represents 11©; 7 represents 8; the bond L hydrogen and some represents Each of them is hydrogen Rg thalogen ve does not exist; TTT represents A and Ao hydrogen each represents hydrogen Ry and Rs Rp m egypt ?And the present invention relates to a method for treating the dysfunction Nationality 0 and in another embodiment (1) in my breasts includes administering to said breast a therapeutic amount of a compound of formula 1 as 2 CH, representing L ¢hydrogen each representing hydrogen Re and Re Rp Re «Rp (Ry) where A is the bond -<-- not present; oN 10 µk

And he gets: * and Ry sR; Ry, each of which represents hydrogen, in a procedure that includes giving the aforementioned thyroid an amount of Val Ladle from a compound of the formula (1) Re Rp “Ra Cus” and JS oes Ca Rp separately from hydrogen or halogen Rg ¢halogen ° represents hydrogen 170:0860; 7 ml; TTT bond not present?; A R X (NL x 7 Jb: ; LX 5 7 N yb and SR; is defined in formula (1). 1 where Re Rp Ra and Rp (JK) choose >33 hydrogen or ¢halogen Re and Re Each represents ¢hydrogen Ra[methaneyl 7 CH; 1; TTT - bond not present; A represents and X = EN 7 TR; N 7; Ry and Rs each represent chydrogen and # represents S veo and in the embodiment of “al » the present choice 2 relates to a method for treating sexual dysfunction in Tadbi that includes administering to the aforementioned gynecomastia an effective amount of ladle of Compound with formula (1) where Re Re Ra and with JS Jus TS separately from hydrogen or halogen Rg thalogen is selected from “alkoxycarbonyl” calkylcarbonyl

Vv cycloalkylcarbonyl ring <arylcarbonyl aryl carbonyl ealkyl alkyl Ja 7 ¢ (NZ Zy)carbonyl (NZ.Z,) or heterocyclecarbonyl carbonyl heterocyclecarbonyl

Jha A not found; TTT; Association B Rie 13

Jy (1) and p as defined by formula Rs (Ra Ry ol Zp of NTR) The present invention relates to a method for the treatment of sexual dysfunction “al” and in embodiment (1) of a compound of formula Ladle JU ad includes giving the aforementioned breast an amount of od in or hydrogen halogen separately from hydrogen (JS) and with a choice of Re Rp Ry where calkylcarbonyl is an alkyl carbonyl “alkoxycarbonyl carbonyl SS” Select from Re thalogen where heterocyclecarbonyl heterocycle carbonyl dala or (NZ,Z;)carbonyl (NZiZ,) carbonyl heterocyclecarbonyl The heterocyclic part of the heterocycle is carbutyl Ve 7 «CH , represents L thydrogen possesses hydrogen, Rp ¢ pyrrolidinyl mentioned is pyrrolidinyl L pyrrolidinyl. Each is hydrogen Rpt 79 N 4 .0 defined in formula 0 of a compound of formula (1) wherein Ladle in my breast involves administering to said mammal an effective amount 'halogen' or 'halogen hydrogen' separately of JS hydrogen Choose > “Rp and Re” Rp Ry ; bond ———— does not exist; 1 Jas 7 hydrogen represents hydrogen Re

Jha AY 01 A

VA

Ra

R 1 welcomed 3

H.N. “Ry

R

(1) is defined in the formula LS Rs and Re Ry Ry na b st 5 The present invention relates to a method for the treatment of sexual dysfunction al and in embodiment of (1) said gynecomastia a therapeutic amount of a compound with the formula elle) in a dew containing or halogen hydrogen from hydrogen daa on JS and with Rc selected for Ry where - bond “CH, comprising 1, ¢ hydrogen, of which hydrogen is Js Jr Re and Re thalogen 2

Jian M SCH not found; 7 represents "2 Ah Bah Rj

TT

3 ~ ~R, . 2 R as Rs sR, and 'hydrogen' each represents hydrogen Ry and Ry «Ry; 5 . (1) by custom in the formula and in another embodiment; The present invention relates to a method for treating said dysfunction with a therapeutically effective amount of a compound of the formula (ol ¢ lac) a nationality in a mixture containing or separately hydrogen halogens of JK hydrogen choosing Rp and Re ( Rp Rp live (1) does not exist; TTT bond “CH represents Z thydrogen represents hydrogen Rg thalogen represents A

Ry TRY (1). or halogen hydrogen separately from hydrogen JS select Ro what and Rp Ry where

Va is mm A the linker “CH, L hydrogen represents hydrogen Logie JS represents Re and Rg thalogen represents A (CH present; 7 represents

Ro

R4 > m 1 5 d “TR Defined in WSR, and thydrogen of which hydrogen is JS Ry and Ry Ry?” nN 4 . (1) Formula 0 of a compound of the formula Ladle mentioned in the amount of Val = X in Dubai includes giving hydrogen or halogen separately from hydrogen BN goa Rp and Re «Rg Rp Cua represents ©; bond ———— present; Z thydrogen is hydrogen Rg ¢halogen ] = 3 A

R2

R 1 and Hb 0 “kd bd” Ry (1) as defined by the formula Rs and Ra (Ry Ry co for Rs 1) The present invention relates to a method for remedying dysfunction 0 and in another embodiment, or hydrogen of Bas hydrogen on JK Sa Rp and Re Rp “Ra of the formula (1) where ¢C equals 7 ¢CH, of which L hydrogen is hydrogen JS represents Re and Rg thalogen halogen present; “TTT bond Vo represents A

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A and M with “Ry <> 7 Ry Ry ¢ Rs and Ry of which JS represents hydrogen ‘hydrogen’ and LS Rs sR, customary in formula (1) and in the embodiment of “AT The present invention relates to a method for the treatment of sexual dysfunction, including sexual dysfunction, in males and females in humans, which includes giving the said humans a therapeutic amount of a compound of formula (1), whereby the said compound in formula (1) is selected from: (4-7-) 7-Methylpiperidinyl (1)piperazinyl](1(methyl)-111-benzimbidazole ¢2-{[4-(3-methylpyridin-2-yl)piperazin-1 -yljmethyl}-1H-benzimidazole 11 (-1-7-benziimidazolyl (¥(methyl)piperazinyl](1)nicotinotrile ¢2-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1-yl]nicotinonitrile 01 © SEY bromo-?-[(“pyridinyl((1-(piperazinyl)))1(methyl]-111-benzo-imbidazole 7-dibromo-2-[(4-pyridin-2-ylpiperazin- 1-yl)methyl [-1H-benzimidazole,£5©-fluoro-7(-pyridinyl)(1) piperazinyl ir EY [dia (1)) imbdazole ¢5-fluoro-2-[(4-pyridin-2-ylpiperazin) -1-y Dmethyl]-1H-benzimidazole D-Jazol 1?thiazolyl (1?)) piperazinyl [(V)menbel)-11-benzimidazole ¢2-{[4-(1,3-thiazol) -2-yl)piperazin-1 -ylJmethy!}-1H-benzimidazole (1-(methyl)]-11-benzimidazole-1-isobutyl 2- [(4-pyridin-2-ylpiperazin-1 -yl)methyl]-1H-benzimidazole-1 carboxylate (se (1) linidilorib(-1-]lithem (0) die (7) di 1 "m Benz 2-[(4-pyridin-2-ylpiperazin-1 -yl)methyl]-1-(pytrolidin-1 -ylcarbonyl)-1H- Jol aad 'benzimidazole 0 dimethyl 1-7-7( - Pyridinyl (Y) piperazinyl (1)(myl]-111-benzimidazole-1-carboxamide N N-dimethyl-2-[(4-pyridin-2-ylpiperazin-1-yhmethyl]-1H -benzimidazole-1-¢carboxamide 1 4 A

methylpiperazin]-11-imisdazole (1); ¥ (methyl)piperazinil 11 tel( ¢2-[4-(1 H-benzimidazol-2-ylmethyl)piperazin-1 -yl]benzonitrile imidazole par HY {de [(V)-(7) -chlorophyll) piperazinyl 4-7 0 ¢2-{[4-(2-chlorophenyl)piperazin-1-ylJmethyl +-1H-benzimidazole 11-benzimidazole {di ](1) dei -(7-fluorophenyl) £¢2-{[4-(2-fluorophenyl)piperazin-1-ylJmethyl}-1 H-benzimidazole 11-methyl imidazole)-](1(-)-(7-nitrophenyl)piperazinyl EY ¢2-{[4-(2-nitrophenyl)piperazin-1-yljmethyl}- 1H-benzimidazole 01-benzimidazole HY = {fe](1)-(7-methetoxyphenyl)piperazinyl 4-7 ¢ 2-{[4-(2-methoxyphenyl)piperazin-1 -ylJmethy!}-1H-benzimidazole lonf])1(methylated)piperazinyl (Y)benz imidase and lyl (HY)mE)¢4-[4- (1H-benzimidazol-2-ylmethyl)piperazin-1-yl]phenol benzimidazole HY methyl)-(1)( 7-((71-4-methylthio)phenyl]piperazinyl ae ¢2- ({4-[2-methylthio)phenyl]piperazin-1-yl} methyl)-1H-benzimidazole

Used sir (m)-(1-(fuse) piperazinyl) on SY) £1) ¢2-{[4-(2-ethoxyphenyl)piperazin-1-yl]methyl}-1 H-benzimidazole ])1( Piperazinil (Sie imidazolyl (1?) 5 HY ) = E] ¢2-[4-(1 H-benzimidazol-2-ylmethyl)piperazin-1-yl]phencl To mel)- 101-Benzimidazole](1(phenyl)piperidinyl aS SY) 1-([?¢2-{[4-(2-methoxyphenyl)piperidin-1-yljmethyl}-1 H-benzimidazole imidazole pum [die (1) piperidinyl (1) pyridinyl (1-7 ¢2-[(4-pyridin-2-ylpiperidin-1-yl)methyl]-1H-benzimidazole methyl]-111 -benzimidazole (HY) 1-linideriborde HET -phenyl-; (1-7 ve ¢2-[(4-phenyl-3,6-dihydropyridin-1(2H)-yl)methyl]-1H- benzimidazole

YAYA

b(Sf)EI pyridinyl (1)) piperazinyl])1(methyl)-111-benz-imbidazole ¢2-{[4-(6-methylpyridin-2-yl)p piperazin-yl]methyl}- 1H-benzim isidazole (Y) Jin pe Ede TY piperazinyl iH) =[ ae ))1( imidazole ¢2-[(2-methyl-4-pyridin-2-ylpiperazin-1 -ymethyl]- 1 H-benzimidazole ?-GZA(?5)-"-methyl-4-pyridinyl (¥) piperazinyl [(1-mec)-111-benzimidazole ¢2-{[(2S)-2-methyl) -4-pyridi n-2-ylpiperazin-1-ylJmethyl}-1 H-benzimidazole 87([(71)-?"-methyl-?-pyridinyl (¥) piperazetyl])1(methyl)-111- Benzimidazole ¢2-{[(2R)-2-methyl-4-pyridin-2-ylpiperazin-1 -yl]methyl}-1H-benzimidazole 5H) = 4-078 imidazolyl (Y)methyl) Piperazinil])1(Pipridil (©)) Mechan 01 Sulfur Nami N-{2-(4-(1 H-benzimidazol-2-ylmethyl)piperazin-1-yl]pyridin-3- a ¢yl}methanesulfonamide 1-7[-(?-fluoropyridinyl (7) piperazinyl])1(meghyl)-pa impidazole ¢2-{[4-(3-fluoropyridin-2-yhpiperazin) -1-yljmethyl}-1 H-benzimidazole or its salt; cester yl amide or a pharmaceutically acceptable prodrug thereof. and human females involves administering said humans a therapeutic dose of IY-pyridinyl(Y)piperazinyl (Te)(1)benzimidazole ¢2-[(4-pyridin-2-ylpiperazin-1-yl)methyl} -1H-benzimidazole or its amide ester salt is a pharmaceutically acceptable primary drug. In another embodiment, the present invention relates to a method for treating sexual dysfunction including sexual dysfunction in males and females in humans comprising administration to said humans of an effective amount of (a)(a)-pyridinyl(V)piperazinil di((a)tartrate) (g) methyl]-111-ptzimidazole 2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1H- .benzimidazole bis((L)tartrate), and in another embodiment. The present invention relates to a method for treating sexual dysfunction, including sexual dysfunction, in males and females in humans comprising the administration of the aforementioned humans

YY

methyl]-(1) “pyrimidinyl (1) piperazinil OY therapeutically from Jad amount or £2-[(4-pyrimidin-2-ylpiperazin-1-yhmethyl]-1H-benzimidazole Benz-imidazole [1

Lia acceptor aia primary Jie or amide amide caster salt; Esther In another embodiment, the present invention relates to a method for the treatment of sexual dysfunction including the aforementioned humans eae) including sexual dysfunction in human males and females comprising °[(1) of a therapeutic amount of acacia 7-41-(111 Benzimidase and Lyl (7) piperazinyl or its salt 6-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1-yl]pyridin-3-ol (¥) pyridinol or a prodrug thereof Pharmaceutically acceptable. amide amide cester ester The present invention relates to a method for the treatment of sexual dysfunction including A) and in an embodiment thereof sexual dysfunction in human males and females includes administration of the aforementioned humans Ve or drug amide amide cester A therapeutic value of a compound of formula ( ) or a salt; Esther

Lisa is an acceptable primary carrier thereof Pharmaceutically acceptable in combination with a carrier The present invention relates to a method for the treatment of sexual dysfunction including al and in embodying sexual dysfunction in human males and females including the administration of said humans of a compound of the form (1) Where the aforementioned compound of the Ladle formula is selected as an effective amount of: (1) methyl)-111-benzimidazole [(1) (*-methylpyridinyl (7) piperazinil 4177 ¢2-{ [4-(3-methylpyridin-2-yl)piperazin-1 -yl]methyl}-1H-benzimidazole nicotinotrile](1)-(111-benzimidazolyl (¥)methyl)piperazinyl 4 IY ¢-2 [4-(1H-benzimidazol-2-ylmethyl)piperazin-1 -yl]nicotinonitrile methyl]-111-benzimidazole (1) piperazinyl (1)bromo-?-[(4-) Pyridinyl (TY©¢5.7-dibromo-2-[(4-pyridin-2-ylpiperazin-1-ylmethyl]-1H-benzimidazole fluoro-41-1-pyridinyl(7)piperazinyl(1)methyl]- 111-benzimidazole ¢5-fluoro-2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1 H-benzimidazole methyl)-111-benzimidazole](1) ddan (1) dissin ¥ (4-1 0 ¢2-{[4-(1,3-thiazol-2-yl)piperazin-1 -yl]methy!}-1H-benzimidazole 1 rt

n"-1); methy!]-1H-benzimidazole-1 -carboxylate IY-pyridinyl(7) done (0) methyl]-1-(pyrroledienyl V(t)1)benzimidazole 2-[( 4-pyridin-2-ylpiperazin-1-y)methyl]-1-(pyrrotidin-1-ylcarbonyl)-1H- ° 60211111206?die JUIN 7-[(;-pyridinyl(Y)piperazinyl ))1(methyl]-111-benzimidazole-1-carbox_samide N N-dimethyl-2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1H-benzimidazole-1-p whip?ha;4-ylpiperazinyl sda dy wr [dbs ))1) ¢2-[(4-phenylpiperazin-1-yl)methyl]-1 H-benzimidazole 01 HY)EY imidazolyl (1) Methyl)piperazin (1)]-benzonitrile H-benzimidazol-2-ylmethyl)piperazin-1-yl]benzonitrile 1(-4[-£2 41-7-(7-chloropene_l)piperazinyl](1) Mel)-HY benzimidazole ¢2-{[4-(2-chlorophenyl)piperazin-1 -yl]methyl}-1H-benzimidazole d-mod = Y)fluorophenyl)piperazinyl [(V) methyl)-iH imidazole ¢2-{[4-(2-fluorophenyl)piperazin-1-yl]methyl}-1 H-benzimidazole (N= -(?-nitrophyl)piperazinyl]) 1(methyl)-111-benzimidazole ¢2-{[4-(2-nitropheny!)piperazin-1-yl]methyl}- 1H-benzimidazole }£1 -("-moxyphenyl) ]) 1(Jip Magisl)-ib Imbesdazole ¢2-{[4-(2-methoxyphenyl)piperazin-1 -yl}methyl}-1H-benzimidazole 0 111-74 Benzimidazole (Jin (1) Perazinyl(1)]phenol ¢4-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1 -yl]phenol 7-((71-4-methylthio)[sé piperazinyl] (1(methyl)-111-benzimidazole ¢2-({4-[2-methylthio)phenyl]piperazin-1-yl} methyl)-1H-benzimidazole ve 41-7-("-ethoxyphenyl ) piperazethyl](1-(methyl)-111b-zimipidazole ¢2-{[4-(2-ethoxyphenyl)piperazin-1 -yl]methyl}-1H-benzimidazole YAYA

Ye Fol])1(methyl)piperazinyl (V)ben-g imidase and lyl [1(1-1 1)-4]-2;H-benzimidazol-2-ylmethyl)piperazin-1- yl]phenol methyl)-111benzymebdazole [(1)sispaphenyl) aS ¥) EI ¢2-{[4-(2-methoxyphenyl)piperidin-1 -yl]methyl}-1H-benzimidazole methyl]-111-benzimidazole (1) piperidinyl (Y) 7-](; -benzimidazole methyl]-111-benzoimbidazole (HY) 1-liondier hydrope IT (mdi "-1[(;¢2-[(4-pheny}-3,6-dihydropyridin-] ( 2H)-yl)methy!]- 1 H-benzimidazole methyl)-111-benzimidazole](1)pyridinyl (7(piperazinyl di) = ED ¢2-{[4-(6-methylpyridin-2) -yl)piperazin-ylJmethyl}-1H-benzimidazole 01-benzimidazole HY mel]-(1) piperazinyl (11) ?-methyl-?-pyridinyl(1-7 ¢-[() 2-methyl-4-pyridin-2-ylpiperazin-1 -yl)methyl]-I H-benzimidazole Methyl)-111-benzimidazole](1) piperazinyl (1)-pyridinyl Edie T(SY) IY¢2-{[(2S)-2-methyl-4-pyridin-2-ylpiperazin-1-yllmethyl}-1H-benzimidazole

Os ad methyl)-111-benz](1) piperazinil (Y) 87([1-7)-7-methyl-?-pyridinyl 00 £2-{ [(2R)-2-methyl) 4-pyridin-2-ylpiperazin-1 -ylJmethyl}-1H-benzimidazole N

N-{2-(4-(1 H-benzimidazol-2-ylmethyl)piperazin-1-yl]pyridin-3- a align pS¢ylymethanesulfonamide methyl)-111-benzoimidazole [(V)fluoropropylridinyl (?)) piperazinil-7( 11-7 ve cester isd or salt; ¢2-{[4-(3-fluoropyridin-2-yl)piperazin-1-ylJmethyl}-1H-benzimidazole or prodrug pharmaceutically acceptable thereof in combination with a pharmaceutically acceptable carrier amid an amide and in another embodiment; the present invention relates to a method for treating sexual dysfunction including sexual dysfunction in human males and females comprising the administration of said humans [myl]-1M - (1) piperazinil (1) -pyridinyl IY therapeutically from JLT d amount

YAYA

AM

or salt; The 2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1H-benzimidazole ester is a pharmaceutically acceptable prodrug thereof in combination with a pharmaceutically acceptable carrier. amide An amide cester The invention relates The current method for the treatment of sexual dysfunction, including 0” and in another embodiment, including sexual dysfunction in males and females, includes administration of the aforementioned humans (7) of Di(1) tartrate) 1-3-Pyridinemyl Ladle amount Potent oo 2-[(4-pyridin-2-ylpiperazin-1-yDmethyl]- 1H-1-methylated benzimidazole]-(1) piperazinil in combination with a pharmaceutically acceptable carrier. benzimidazole bis ((L)tartrate) In another embodiment, the present invention relates to a method for the treatment of sexual dysfunction including sexual dysfunction in males and females in humans comprising the administration of said humans as an amount of [methyl]-111-benzimbidazole (1) Therapeutically effective 1-(7-pyrimidinyl)(7) piperazinyl 0 or its salt; ester type amide 2-[(4-pyrimidin-2-ylpiperazin-1-yl)methyl]-1H-benzimidazole or drug The present invention relates to a method for the treatment of sexual dysfunction including aT and in embodying sexual dysfunction in human males and females involving the administration of said humans [(1) an amount Therapeutic value of 41-76 -(111-benzimidazolyl)¥ (methyl) piperazinil ae or its salt 41 H-benzimidazol-2-ylmethylpiperazin-1-yl]pyridin-3-ol (7) piperidinol drug Pharmaceuticalally acceptable oleoresin in combination with a pharmaceutically acceptable carrier sf amide amide cester ester. It includes giving said humans x. or a drug amide cester A therapeutically effective amount of a compound of formula (1) or a salt; a primary Lay fe phosphodiesterase 5 (©) ester thereof Pharmaceutically acceptable in combination with or vardenafil sildenafil Sildenafil « ja all in it; for example, not Le inhibitor vardenafil . The present invention relates to a method for the treatment of sexual dysfunction including “5ST” and in an embodiment of ve including sexual dysfunction in human males and females includes the administration of the aforementioned humans

Y4YA

b The amount of Ladle Jad from a compound of formula (1) where the compound mentioned in formula (1) is chosen from: (dims Sie) (7) piperazinil [(1)methyl)-111-benzymedazole 2-methylpyridin -yl)piperazin-1 -ylJmethy!}-1H-benzim idazole 4-3])-2; oe 1-benzimidazolyl (7(methyl)piperazinyl](1)nicotinotrile ¢2-[4-(1H-benzimidazol-2-y Imethyl)piperazin-1-y [Jnicotinonitrile] © STV Promo 7-7-[(?-pyridinyl)¥( piperazinyl ))1(mgyl]-111-benzimidazole 7_dibromo-2-[(4-pyridin-2-ylpiperazin-1 -yl)methyl]- 1H- benzimidazole ,5?de mY mse(1)piperazinyl(1( Js ad 5H) “ld ¢5-fluoro-2-[(4-pyridin-2-ylpiperazin-1 -yl)methyl]- 1 H-benzimidazole 01 "-([;-(-((Y) dds piperazinyl])1(methyl)-111-benzyimidazole -thiazol-2-y!)piperazin-1-ylJmethyl} 1-H-benzimidazole 1.,3(-4[{-2 17(-pyridinyl (?)))1(dls methyl]-111-benziimidazole-1-carboxylate ¢isobutyl 2- [(4-pyridin-2-ylpiperazin-1 -yl)imethyl]-111-benzimidazole- 1-carboxylate HIT ve pyridinyl (1) piperazinyl ld ))1 (pyrrolidinyl (1) carbonyl)-1-benzimbidazole 2-[(4-pyridin-2-ylpiperazin-1-yhmethyl]-1-(pyrrolidin-1-ylcarbonyl)-1 H-¢benzimidazole SUNN methyl-?- [((Y) dont piperazinil))1(methyl]-111-benzimidazole-1-carbox_samide N.N-dimethyl-2-[(4-pyridin-2-ylpiperazin-1-yDmethyl]-1H -benzimidazole-1- ¢carboxamide 1 ?-[(; Phenylpiperazin (1)methyl]-111 benz so sed ¢2-[(4-phenylpiperazin-1 -yD)methyl]-1H-benzimidazole 477 -(111-benzimidazolyl (7)methyl) piperazinyl(1)]-benzonitrile H-benzimidazol-2-ylmethyl)piperazin-1 -yl]benzonitrile 1(-4[-2 ve 41-7(chloronyl)piperazinyl])1(methyl) -111 yor imbdazole ¢2-{[4-(2-ch lorophenyl)piperazin-1-yl] methyl}-1H-benzimidazole G01

Ya

imidazole rH {drie ](1-(fluorophenyl)piperazinyl-7) 177 ¢2-{[4-(2-fluorophenyl)piperazin-1-yljmethyl}-1 H-benzimidazole methyl)-ben imidazole ](1) piperazinyl (i mY) EY ¢2-{[4-(2-nitrophenyl)piperazin-1-ylJmethyl}-1 H-benzimidazole lambdazole 5H){Ba](1) -(7 piperazinyl) 41-7 000 2-{[4-(2-methoxyphenyl)piperazin-1 -yl]methyl}-1H-benzimidazole Fqol 1(methyl)piperazinyl (Y) Imidazolyl (5H)-2-4 ¢4-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1 -yl]phenol (syl)-111-benzimidazol (1) piperazinyl [J 7-(4-methylthio-71)¢2-({4-[2-methylthio)phenyl]piperazin-1 -yl}methyl)-1H-benzimidazole 01 chel)-111-benzimidazole](1) -(7-ethoxyphenyl)piperazinyl £1) ¢2-{[4-(2-ethoxyphenyl)piperazin-1-yljmethyl}-1 H-benzimidazole [(1) imidazolyl (7) mvl) Piperazinil (SHY) ET¢2-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1 -yl]phenot imidazole benz 111 {Ba[())-(7-methoxyphenyl)piperidinyl 41- 7 0 ¢2-{[4-(2-methoxyphenyl)piperidin-1-yl]methyl}-1 H-benzimidazole Benzimidazole HD MFL]-(1)(piperidinyl (¥)dr) - (1-7¢2-[(4-pyridin-2-ylpiperidin-1-yl)methyl]-1 H-benzimidazole methyl]-111-benzimidazole (HY) 1-linideriborde SU -phenyl-”; (1-7 ¢ 2-[(4-phenyl-3,6-dihydropyridin-1(2H)-yl)methyl]- 1H-benzimidazole 00 methyl)-111-benzimidazole](1) -( >-Mephylpyridinyl (7) piperazinyl 11-1 ¢2-{[4-(6-methylpyridin-2-yl)piperazin-yljmethyl}-1 H-benzimidazole -benzimidazole HY methyl]-)) 1( “-[(7-methyl-4-pyridinyl)¥) piperazinyl ¢2-[(2-methyl-4-pyridin-2-ylpiperazin-1-yh)methyl]-l H-benzimidazole

Js sad 3H {dia ](1) piperazinil (1) 7-[(57)-1-methyl-?-pyridinyl ve ¢2-{[(28)-2-methyl-4-pyridin-2 -ylpiperazin-1-ylJmethyl}-1 H-benzimidazole as va methyl)-111-benzimbidazole](1) piperazinyl (1)([(7)-1-methyl-?-pyridinyl) ¢2-{[(2R)-2-methyl-4-pyridin-2-ylpiperazin-1 -ylJmethyl}-1H-benzimidazole pyridinyl ())methane])1(methyl)piperazinyl (Y) Benz-Imidazolyl 11-41-71

N-{2-(4-(1H-benzimidazol-2-ylmethyl)piperazin-1-yl]pyridin-3- a guys ¢yl}methanesulfonamide c-megyl)-111-benzimidazole](1) piperazinyl ((Y) -(?-fluoropyridinyl EY cester rl or salt; ¢2-{[4-(3-fluoropyridin-2-yl)piperazin-1-ylJmethyl}-1H-benzimidazole (0) or A pharmaceutically acceptable prodrug thereof in combination with a phosphodiesterase inhibitor camide amide sildenafil including but not limited to;0 sildenafil “ells including phosphodiesterase 5 vardenafil vardenafil 01 An embodiment of this in male and female sexual dysfunction includes administration of said humans “HY [die (1) a therapeutic amount of 7-[(4-pyridinyl) (7) piperazinil or salt; 2-[(4-pyridin-2-ylpiperazin-1-yhmethyl]-1H-benzimidazole ester benz imidazole (6) or a pharmaceutically acceptable prodrug thereof in combination with a phosphodiesterase inhibitor amide seser 0 vardenafil vardenafil sildenafil including sildenafil Lephosphodiesterase 5 and in another embodiment; the present invention relates to a method for the treatment of sexual dysfunction including sexual dysfunction in human males and females comprising the administration of said humans (7-[(4-pyridinyl) tartrate) (?) Piperazinil (L)) A therapeutically effective amount of 2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]- 1H-benzimidazole imdazole oH [die ((V) Yo Including; Les phosphodiesterase 5 (©) in combination with a phosphodiesterase inhibitor bis((L)tartrate) vardenafil or vardenafil sildenafil to name a few; sildenafil and in another embodiment; The present invention relates to a method for the treatment of sexual dysfunction in human beings and females that includes administering the aforementioned human So including sexual dysfunction in menthyl]-(1) piperazinil (1) therapeutically from 7-[(4) Jind-pyrimidinyl ve or salt; 2-[(4-pyrimidin-2-ylpiperazin-1-yl)methyl]-1H-benzimidazole imidazole Znb-111 rv. or an acceptable prodrug thereof pharmaceutically in combination with a phosphodiesterase inhibitor amide coster ester or sildenafil including, but not limited to sildenafil phosphodiesterase 5 (°) vardenafil and in another embodiment the present invention relates to a method for treating an impairment Sexual function, including sexual dysfunction in human males and females, includes administering the aforementioned humans ° [(1 methyl) piperazinil (Y) dads aed 33m HD ) E177 therapeutically from Jd amount or salt 6-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1-yl}pyridin-3-ol (90 pyridinol or a pharmaceutically acceptable prodrug thereof in combination with an amide cester inhibitor) Jaw includes but is not limited to La phosphodiesterase 5 (©) vardenafil or vardenafil sildenafil Ve and in another embodiment the present invention relates to a method for the treatment of sexual dysfunction including dysfunction Sex in human males and females includes administering to humans said amide 06 or cester drug (rela from a compound of formula 0) or Ladle JL xd a pharmaceutically acceptable initial amount thereof in combination with an adrenergic receptor antagonist including This is based on, but not limited to, tamsulosin, prazosin, or sterazosin. terazosin dase AA and in another embodiment the present invention relates to a method for treating sexual dysfunction including sexual dysfunction in males and females in humans involving administration to said humans from a compound of formula (1) wherein said compound of formula is selected Ladle separated amount of: (1) ad mH {in ])1( -("-(1-methylpyridin)) piperazinil 4011-7 ¢2-{[4-(3-methylpyridin-2-) yl)piperazin-1-yl]methyl}-1 H-benzimidazole nicotinonitrile](1)benzimidazolyl)¥(methyl)piperazinyl 111-41-7 ¢2-[4-(1H-benzimidazol-2-) ylmethyl)piperazin-1-yl]n icotinonitrile methyl]-111-benzoimbidazole (1)bromo-1-7-7)-pyridinyl (7) piperazinyl SEY ©. ve ,5? 7-dibromo -2-[(4-pyridin-2-ylpiperazin-1-ylymethyl]- 1H-benzimidazole

YAYA

Os ed methyl]-111-benz (1) ; H-benzimidazole mgl)-111-benzimidazole [(1) 7-([;-(1;-thiazolyl(1))) piperazinyl £2-{[4-(1,3-thiazol-2-yl) (piperazin-1-yl] methy!}-1H-benzimidazole methyl]-111-benzoimidazole-1-isobutyl carboxylate (1) ?-pyridinyl (7) piperazinyl [1-1 oe ¢isobutyl 2- [(4-pyridin-2-ylpiperazin-1 -yl)methyl]-1H-benzimidazole-1 -carboxylate “HY (tS (1) linidilorib(-1-]lithem (0)a?pyridinyl (7) piperazinyl) 2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1-(pyrrolidin-1-ylcarbonyl)- 1H-benz imidazole 66021010206 -1-lozademia HY [die ))1( Piperazinil (Y) 800<-dimethyl 777(-pyridinyl 00 0

N,N-dimethyl-2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1H-benzimidazole-1-carboxamide ¢carboxamide 11-megyl-benzimidazole]-)) 1) Fyl-Piperazinil 7-7 ¢2-[(4-phenylpiperazin-1-yl)methyl}-1 H-benzimidazole lerctnonozeb-](1) Piperazinyl (Jie (7) 11D-benzimidazole) - Gel 2-[{4-(1H-benzimidazol-2-ylmethyl)piperazin-1 -yl}benzonitrile methyl)-111 benzimidazole](1)rophenyl)piperazinyl ITY) EIT ¢2-{ [4-(2-chlorophenyl)piperazin-1-yl]methyl}-1 H-benzimidazole imidazole sar methyl)-])1(-(7-fluorophyll)piperazinyl 4-7 ¢2-{ [4-(2-fluorophenyl)piperazin-1 -ylJmethyl}-1H-benzimidazole A Benzimidazole HY Mel)- [(V)piperazinyl (Ji 25 Ym 4-7 ¢2-{[4- (2-nitrophenyl)piperazin-1 -yl]methyl}-1H-benzimidazole imbdazole 5H methyl)-])1(-(?-methoxyphenyl)piperazinyl 21-7 ¢2-{[4- (2-methoxyphenyl)piperazin-1-ylJmethyl}-1 H-benzimidazole phenol [(V)methyl)piperazinyl (¥) dds Pred Sm YEE 0 ¢4-[4-(1H-benzimidazol-2-ylmethyl) )piperazin-1-yl] phenol 1 occurs

YY

Impedazole yr (methylthio)-()("-(71-40-methylthio)phenyl]piperazinyl ¢2-({4-[2-methylthio)phenyl}piperazin-1-yl} methyl) 1H-benzimidazole methyl)-11-benzimidazole](1)-(7-ethoxy-ph)piperazinyl 41-7 ¢2-{[4-(2-ethoxypheny!)piperazin-1-yl]methyl} 1-H-benzimidazole piperazinyl(1([fifol(7)-benzimidazolyl 1"H0¢2-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1 -yl} phenol impidazole en Mgipsil)-(1-(7-methoxyphenyl)piperidinyl 1-7 ¢2-{[4-(2-methoxyphenyl)piperidin-1-ylJmethyl}-1 H-benzimidazole

Jaded Mel]-11-benz (1) piperidinyl (Y) (pyridinyl (1-7 ¢2-[(4-pyridin-2-ylpiperidin-1-yl)methyl]- 1 H- benzimidazole 01 methyl]-111 benzimidazole (HY) 1-hydropyridine SET “-[(?-phenyl-” ¢2-[(4-phenyl-3,6-dihydropyridin-1(2H)) -yhmethyl]-1 H-benzimidazole 111-benzimbidazole {a])1(piperazetyl ((Y) -(>-methylpyridinyl [1-7 ¢2-{[4-(6-methylpyridin)) -2-yl)piperazin-yl]methyl}-1 H-benzimidazole -2-ylpiperazin-1-yl)methy!]-I H-benzimidazole methyl)-111-benzimidazole](1) piperazinyl (1)(7-([(57)-7-megyl-; 2-pyridinyl ¢-{[(28)-2-methyl-4-pyridin-2-ylpiperazin-1-ylJmethyl}-1 H-benzimidazole methyl(111-benzimidazole](1) 1-) [(87)-1-methyl-;

Oise (7) pyridinyl [(1) benz-imidazolyl (7(methyl) piperazinyl HY mE] TIN

N-{2-(4-(1H-benzimidazol-2-ylmethyl)piperazin-1-yl]pyridin-3-D-¢yl sulfur } methanesulfonamide methyl)-111-benzimbidazole](1)piperazinyl ((Y) dss $8) 41-7 cester or salt; best ¢2-{[4-(3-fluoropyridin-2-yl)piperazin-1-yl]methyl}-1H-benzimidazole Ye is better than it Pharmaceutically acceptable in combination with an adrenergic receptor antagonist signaling lie or amid amide vy prazosin sterazosin including, but not limited to, tamsulosin or prazosin and in other embodiments The present invention relates to a method for the treatment of sexual dysfunction including sexual dysfunction in males and females in humans comprising the administration of said humans “HY [die [1] piperazinil (1)-pyridinyl IY of Ladle amount Val 0 or salt; ester 2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1 H-benzimidazole benzimidazole or a pharmaceutically acceptable prodrug thereof in combination with an adrenergic receptor antagonist amide cester prazosin prazosin cterazosin excitability including; Human males and females includes administering piperazinil (Y) to the aforementioned humans with a therapeutically effective amount of (1)-(7-) tartrate; -Pyridinyl 2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1H-benzimidazole methyl]-111-benzimidazole ((V) in combination with an excitatory adrenergic receptor antagonist incl. For example ¢his((L)tartrate) tamsulosin or tamsulosin prazosin cterazosin terazosin andl eg no Ve and in another embodiment; the present invention relates to a method for treating sexual dysfunctions including Sexual function in human males and females includes giving said humans methyl]-(1) piperazinil (Y) of 7-[;-pyrimidinyl Ladle amount of Val or salt; 2-[( 4-pyrimidin-2-ylpiperazin-1-yDmethyl}-1H-benzimidazole imidazole HD or a pharmaceutically acceptable prodrug thereof in combination with an amide receptor antagonist cester wd cterazosin in it; to name a few Lay-adrenergic excitatory tamsulosin or prazosin prazosin In another embodiment, the present invention relates to a method for the treatment of sexual dysfunction including sexual dysfunction in human males and females involving the administration of said humans [1] (methyl) piperazinil (1) therapeutically effective amount of 7-41-(111-benzimidazol-yl-ve or salt; 6-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1-yl ]pyridin-3-ol (¥) pyridinol 1M ve

Aloamide 20108 or a pharmaceutically acceptable prodrug thereof in combination with an adrenergic sterazosin ester antagonist including; For example but not limited to; tamsulosin or prazosin and in another embodiment the present invention relates to a method for treating sexual dysfunction including sexual dysfunction in males and females of humans comprising the administration of said humans or an amide drug coster ind amount of therapeutically from a compound of Formula (1) or its salt; in combination with a dopaminergic agonist including, but not limited to, apomorphine; apomorphine; and in another embodiment the present invention relates to a method for Sexual function, including sexual dysfunction, in males and females of humans includes administration of said humans, ye, the aforementioned compound of formula ia, a therapeutically effective amount of a compound of formula (1) where from: (1) methyl)-111 1-benzimidazole](1)-((-methylpyridinyl (7)) piperazinyl 11-1 ¢2-{[4-(3-methylpyridin-2-yl)piperazin-1-ylJmethyl}-1 H-benzimidazole Nicotinonitrile](1) desi-(101-benzimidazolyl)¥(methyl) 41-7 0 ¢2-[4-(1 H-benzimidazol-2-ylmethyl)piperazin-1-yl]n icotinonitrile methyl] -111-benzimidazole (1) piperazinyl (Y)bromo-?-[(?-pyridetyl) (oY 8; ¢5, 7-dibromo-2-[(4-pyridin-2) -ylpiperazin-1-yl)methyl]-1 H-benzimidazole methyl]-111-benzimidazole (1) piperazinyl (Y)fluoro-8)-pyridinyl 5¢5-fluoro-2-[ (4-pyridin-2-ylpiperazin- 1-yl)methyl]-1H-benzimidazole 7-methyl)-141-benzimidazole[(1)"-thiazolyl(1)piperazinyl(21-7¢2-{] 4-(1,3-thiazol-2-yl)piperazin-1-yl]methyl}-1 H-benzimidazole methyl]-111-benzimidazole-1-isobutylcarboxylate (1)(-pyridinyl(7) Piperazinil (1-7-tisobutyl 2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1 H-benzimidazole-1-carboxylate

YAYA

and di (1-1 (7) piperazinyl (1) linadilorib(-1-]lithium) (1(carbonyl)-11-benz 2-[(4-pyridin-2-ylpiperazin-1-yl) )methyl]-1 -(pyrrolidin-1-ylcarbonyl)-1H- Js aad benzimidazole 0<dimethyl-7-[(;<pyridinyl(1)piperazinyl)(1(methyl)]-111 -benzimidazole-1-°carbox_samide N.N-dimethyl-2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]- 1H-benzimidazole-1- ¢carboxamide 7-[(- 1-methyl piperazinyl rH [ie )) 2-(4-phenylpiperazin-1-yl)methyl]-1 H-benzimidazole solution (1) methyl (1)benz-imidazole (demi i ) 1)]-benzontrile ¢2-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1 -yl]benzonitrile 01 1-7 -(7-chlorophene_l)piperazinyl])1(unmethylated)- 111-Benzimidazole ¢2-{[4-(2-chlorophenyl)piperazin-1-ylJmethyl}-1 H-benzimidazole 2-7-(7-fluorophenyl)piperazinyl [(V)methyl)- 5am HY imidazole ¢2-{[4-(2-fluorophenyl)piperazin-1-yljmethyl}-1H-benzim idazole (Jy mY) 40-7 ve piperazinyl [(V)methyl)-111- 2-benzimidazole ¢-{[4-(2-nitrophenyl)piperazin-1-yljmethyl}-1 H-benzimidazole 41-7-(7-moxyphenyl)piperazinepisil])1(dimethyl)-mH Imbledazole ¢2-{[4-(2-methoxyphenyl)piperazin-1-yl]methyl}-1H-benzim idazole 111-74 petzimidazolyl (Y)methylated)piperazin Js 3 3 ](1) ¢4-[4-(1H benzimidazol-2-ylmethyl)piperazin-1-yl]phenol ~~ 00 Jia YI 8 thio)[J piperazinyl]1(methyl)-111- Benzimidazole ¢2-({4-[2-methylthio)phenyl]piperazin-1-yl} methyl)-1 H-benzimidazole 1-7[-(7-ethoxyfil)piperazinyl](1)methyl )- rH imbidazole $2-{[4-(2-ethoxyphenyl)piperazin-1-ylJmethyl}-1 H-benzimidazole ve 7?-[4-(111-benzimidazolyl (7(mil))[ (V) din vol ¢2-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1-yl]phenol as a substitute

™ 1-4-(7-methoxyphenyl)piperidinyl])1(myl)-111-benzimidazole ¢2_{[4-(2-methoxyphenyl)piperidin-1-ylJmethyl}-1 H-benzimidazole" 7 (pyridinyl (7) piperidinyl 5am HY [dia ))1) imbdazole ¢2-[(4-pyridin-2-ylpiperidin-1-yl)methyl]-1 H-benzimidazole SET Fda mY hyde Rubyridinyl-1 sar HY [fie (HY)imildazole ¢2-[(4-phenyl-3,6-dihydropyridin-1 (2H)-yl)methyl]-1H-benzimidazole JT) [7-7 Pyridinyl(7)piperazinyl](1(methyl)-111-benz Os iad ¢2-{[4-(6-methylpyridin-2-yl)piperazin-yl]methyl}-1H-benzimidazole 77("-methyl-4-pyridinyl (7(piperazinyl))1(menyl]-111-benzimidazole ¢2-[(2-methyl-4-pyridin-2-ylpiperazin-1-yl)methyl ]-1 H-benzimidazole 01 "-(57(1)- 7-methyl-4-pyridinyl(?)piperazinyl rH){de ](1)imidazole ¢2-{[(2S)-2- methyl-4-pyridin-2-ylpiperazin-1 -ylJmethyl}-1H-benzimidazole 7-([(87)-7-methyl-?-pyridinyl)7(])1(ds-methyl)-111-benz Impidazole £2-{[(2R)-2-methyl-4-pyridin-2-ylpiperazin-1 -ylJmethyl}-1H-benzimidazole ve 8-(41-7-(111-benzimidazolyl)(7) methyl)piperazinyl [(1) pyridinyl (7){totamethane N-{2-(4-(1H-benzimidazol-2-ylmethyl)piperazin-1-yl]pyridin-3- a tyl} methanesulfonamide 41-7 -( 7-fluoropyridinyl (((Y)piperazinyl])1(methyl)-5am HY imidazole ¢2-{[4-(3-fluoropyridin-2-yl) piperazin-1-yljmethyl}-1 H-benzimidazole or its salt; cester yl > a camide or a pharmaceutically acceptable prodrug thereof in combination with a dopaminergic agonist including; For example but not limited to; apomorphine .and in the aT embodiment, the present invention relates to a method for the treatment of sexual dysfunction including sexual dysfunction in males and females of humans comprising the administration of said humans with a therapeutic value of 7-[(;-pyridinyl(7) piperazinil HY [te ))1( Yo benzimidazole ¢2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1H-benzimidazole or YAYA i salt

An amide aul ester or a pharmaceutically acceptable prodrug thereof in combination with a dopaminergic agonist including; For example but not limited to; apomorphine .apomorphine and in another embodiment; The present invention relates to a method for the treatment of sexual dysfunction including sexual dysfunction in males and females in humans comprising the administration of said human beings with a ladle effective amount of di((1)tartrate) 7-[(;-pipredenisyl (Y) piperazinil 1(methyl]-11-benzimidazole 2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1H-tbenzimidazole bis((L)tartrate) in combination with A dopaminergic agonist including, without limitation, cell; apomorphine .apomorphine and in another embodiment; the present invention relates to a method for the treatment of sexual dysfunction including 0 including sexual dysfunction in human males and females involving the administration of said humans of an amount Val Ladle of 1-7(-pyrimidinyl)1(piperazinyl))1(methyl]-[1-benzimidazole ¢2-[(4-pyrimidin-2-ylpiperazin-1-yl) methyl]-1H-benzimidazole or its salt; an amide ester or a pharmaceutically acceptable prodrug thereof in combination with a dopaminergic agonist including, but not limited to apomorphine .eo and in another embodiment The present invention relates to a method for the treatment of sexual dysfunction including sexual dysfunction in males and females in humans comprising the administration of said humans a therapeutic amount of 7-[4-(111-benz-imidazolyl (7(methyl)piperazinil](1) Pyridinol (¥) 6-[4-(1H-benzimidazol-2-ylmethylpiperazin-1-yl]pyridin-3-ol or a pharmaceutically acceptable prodrug thereof in combination with a binder dopaminergic xo including; including but not limited to .apomorphine and in another embodiment; The present invention relates to a method for treating erectile dysfunction in a human male comprising administration of said human male in need of such treatment a therapeutic Jad of a compound of formula (I) or salt; An ester, an amide, or a pharmaceutically acceptable prodrug thereof. Yo and in another embodiment » The present invention relates to a method for treating erectile dysfunction in a human male that includes giving the human male YAYA

Ya

From a compound of the formula Ladle, which is in need of this treatment, an effective amount, where the compound mentioned in the formula ( ) is selected from: (1) methyl)-111-benzimibazole[(1)(pyridinyl (1)) Piperazinil Jem) DY ¢2-{[4-(3-methylpyridin-2-yl)piperazin-1 -ylJmethyl}-1H-benzimidazole nicotinonitrile])1(methyl)piperazinyl (Y) 41-7 -(111-benzyimidazolyl 0¢2-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1 -yl]nicotinonitrile methyl]-111-benzimidazol (1)(-pyridinyl(?)piperazinyl) 4)] Ym bromo SEV 0 ¢5, 7-dibromo-2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1 H-benzimidazole methyl]-111-benzimidazole )) 1) ©-fluoro-1,7-(-pyridinyl (¥) piperazinil

S-fluoro-2-[(4-pyridin-2-ylpiperazin-1-yl)methyl}-1H-benzimidazole 001 benz imidazole HY {die ](1) 7-thiazolyl (1) piperazinyl (4-) 7 ¢2-{[4-(1,3-thiazol-2-yl)piperazin-1-ylJmethyl}-1 H-benzimidazole methyl]-111-benzimidazole-1-isobutylcarboxylate ((V)piperazinyl (Y) denon "-(; tisobutyl 2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1 H-benzimidazole-1-carboxylatc

SHY (isn S(1) linidlorib(-1-[lithem))1(pyridinyl(7)piperazinyl(01-7 ve 2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]- 1-(pyrrolidin-1-ylcarbonyl)-1H-benz-imibebdazole ?6112111011206 -1-lozademia rH[de)1(piperazinyl(1)L-dimethyl-7-[(;-pyridinyl) ,

N N-dimethyl-2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1H-benzimidazole-1- carboxamide ?; 1) phylylpiperazin EY ¢2-[(4-phenylpiperazin-1-yl)methyl]-1H-benzimidazole lertnosineb-])1(imidazolyl)¥(methyl)piperazin HY) = 2 ¢2-[4 -(1H-benzimidazol-2-ylmethyl)piperazin-1-yl] benzonitrile imidazole rH) {dia [(V)chlorophenyl)piperazinyl (41-7 ve ¢2-{[4-(2-chlorophenyl) piperazin-1-ylJmethyl}-1H-benzimidazole

YAYA

41-7 -(7-fluorophenyl)3am {dre [(V)di J an imbdazole ¢2-{[4-(2-fluoropheny!)piperazin-1-yl]methyl}-1H-benzimidazole 41-7-(7-nitrophenyl)piperazinyl])1(methyl)-111-benzimidazole ¢2-{[4-(2-nitrophenyl)piperazin-1-ylJmethyl}-1H-benzimidazole 6 40 -7 -(7-methoxyphenyl)piperazinyl yur HY {dha [(V)imidazole ¢2-{[4-(2-methoxyphenyl)piperazin-1-yl]methyl}- 1H-benzimidazole 4 ] £ -(111-benzimidazolyl (Y)methyl)piperazinyl (1)]!phenol ¢4-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1-yljphenol 7-(40- [7-Methyl-8(Phil] “HY (Je {(V) Su mn 01 benzimidazole ¢2-({4-[2-methylthio)phenyl]piperazin-1-yl} methyl)-1H -benzimidazole 4-7-(7-ethoxyphenyl)piperazin HY {df ](1) > imidazole ¢2-{[4-(2-ethoxyphenyl)piperazin-1-yl]methyl}-1H-benzimidazole 1-7-(111-benzimidazolyl (7(methyl)])1( ddl phen ¢2-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1-yl]phenol ve 4-7-(7-methoxyphenyl)piperidinyl])1(mel)-111-benzimidazole ¢2-{[4-(2-methoxyphenyl)piperidin-1-ylJmethyl}-1H-benzimidazole 7-[(4-(pyridinyl (?) piperidinyl))1(methyl]-HY-benzimidazole ¢2-[(4-pyridin-2-ylpiperidin-1-ylymethyl]-1H-benzimidazole 7-[(? -phenyl-” JET hydropyridinyl-1 (HY)methyl]-111-benzimidazole ¢2-[(4-pheny!-3,6-dihydropyridin-1(2H)-yl)methyl] -1H-benzimidazole 7 Jf)EY pyridinyl(?)) piperazinyl])1(methyl)-111-benz imbdazole ¢2-{[4-(6-methylpyridin-2-yl)piperazin- yl]methyl}-1H-benzimidazole “7-[( 7-methyl-4-pyridinyl)¥(piperazinyl) 1(methyl]-111-benzimidazole ¢2-[(2-methyl-4) -pyridin-2-ylpiperazin-1-yl)methyl]-1 H-benzimidazole vs 87(10-7)-7-methyl-?er (¥) piperazinyl [(1-methyl)- 111-Benzimibidazole ¢2-{[(2S)-2-methyl-4-pyridin-2-ylpiperazin-1-ylJjmethyl}-1H-benzimidazole mkha

0 dem Y= (RY)-pyridinyl(1)piperazetyl])1(methyl)-111 benz imbladazole ¢2-{[(2R)-2-methyl-4-pyridin-2-ylpiperazin-1 -ylJmethyl}-1H-benzimidazole (4) 41-7 -(111-benz Js dad (?)methyl) piperazinyl [(1) pyridinyl (7){N-{2-()-(2-) 4-(1H-benzimidazol-2-ylmethyl)piperazin-1-ylJpyridin-3- ¢yl}methanesulfonamide 2 1-7 -(7-fluoropyridinyl (?)) piperazinyl Jaa ir HY {de ](1) ¢2-{[4-(3-fluoropyridin-2-yl)piperazin-1-ylJmethy!}-1H-benzimidazole or its salt; ester yi an amide or a pharmaceutically acceptable prodrug thereof. Other; the present invention relates to a method for treating Pal1 erectile function in a human male comprising administration of said human male in need of such treatment a Ladle's potency of H-(pyridetyl) (Y) piperazinil (1) methyl]-11-benzipiptazole 2-[(4-pyridin-2-ylpiperazin-1- yl)methyl}-1H-benzimidazole or salt; cester amide or drug An initial of which is acceptable and in another embodiment the present invention relates to a method for treating erectile dysfunction in a human male comprising administration of said human male in need of such treatment Val Ladle's amount of — (() tartrate) 7-[(; Pyridinyl (1) piperazinyl (1)methyl]-111-benzimidazole .2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1H-benzimidazole bis((L)tartrate (9) In another embodiment, the present invention relates to a method for treating erectile dysfunction in a human male comprising administration of said human male in need of such treatment a therapeutically valid amount of 7-[(©-pyrimidinyl (7) piperazinil)(1) Michel]-SiH) imidazole 2-[(4-pyrimidin-2-ylpiperazin-1-y))methyl}-1H-benzimidazole or its cester amide salt or a pharmaceutically acceptable prodrug thereof. Yo In another embodiment, the present invention relates to a method of treating erectile dysfunction in a human male that involves giving said human male who is in need of such treatment

0 amount of val bade of 41-7 -(111-benzimidazolyl (7) (ie piperazinyl])1(pyridinol H-benzimidazol-2-ylmethyl)piperazin-1-yl]pyridin-3- ol (9) 1)-4]-6 or salt; The cester amide is a pharmaceutically acceptable primary drug. In another embodiment, the present invention relates to a method for treating female orgasm8 (female anorgasmia, clitoral erectile insufficiency, vaginal engorgement, dyspareunia, painful gallbladder spasm5) + in The purest human beings include giving the said most estranged human beings who are in need of this treatment an effective amount of a compound of formula (1) or le cester amide or a pharmaceutically acceptable prodrug thereof.

A 01 embodiment al The present invention relates to a method for treating anorexia in (UY) clitoral erectile dysfunction; Vaginal engorgement Dyspareunia or painful breech spasm in a human female involves administering said human female who is discontinuing to this treatment a therapeutically effective amount of a compound of formula (1) where Sta is the said compound of formula (1) of:

ve 40-7 -(-methylpyridinyl ))1( piperazinyl yim HY {de ])1(imbsidazole ¢2-{[4-(3-methylpyridin-2-yl)piperazin-1- yljmethy!}-1H-benzimidazole 111-4177 benzimidazolyl (1(methyl)piperazinyl](1)nicotinotrile ¢2-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1-yl ]nicotinotrile 0 1-dibromo-7-[(4-pyridinyl(7)piperazinyl((V)methyl]-111-benzimidazole

7-dibromo-2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1H-benzimidazole 7,¢5©-fluoro-7-[(-pyridinyl (?) piperazinyl)) 1(myl]-11-benzimidazole ¢5-fluoro-2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]- 1H-benzimidazole 4-7 -(;))1( dds piperazinyl])1(methyl)-11-benzimidazole ¢2-{[4-(1,3-thiazol-2-yl)piperazin-1-yl]methyl}-1H-benzimidazole

E11 ve-pyridinyl(7)piperazinyl (1)methyl]-111-benzoimidazole-1-abzobutyl carboxylate 2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]- 1H-benzimidazole-1-carboxylate

YAY A

“7[(;-pyridinyl(7)piperazetyl(1) linadilorib(-1-[lithem))1(carbonyl)-111-benzimbidazole 2-[(4-pyridin-2-ylpiperazin-1-) yl)methyl]-1-(pyrrolidin-1-ylcarbony!)-1H-602110102206 ? 01-dimethyl77-[(;-pyridinyl(7)piperazinyl)((1)methyl]-111-benzimidazole-1-°carbox_samide N,N-dimethyl-2-[(4-pyridin-2-ylpiperazin) -1-yl)methyl]-1H-benzimidazole-1- ¢carboxamide 7-[(;-phenylpiperazinyl) 1(methyl]-1-benbenzimbidazole ¢2-[(4-) phenylpiperazin-1-yl)methyl]-1H-benzimidazole "-[4-(111-benz-imidazolyl (Y)methyl)piperazinyl(1)]-benzontrisil ¢2-[4-(1H-benzimidazol) -2-ylmethyl)piperazin-1-yl]benzonitrile 0.1 11-7 -(7-chlorophenyl)piperazetyl {dia ])1( 111-benzimidazole ¢2-{[4-(2-chlorophenyl) piperazin-1-yl]methyl}-1H-benzimidazole 41-7 -(7-fluorophenyl)piperazine ir HV {02a [(V)imidazole £2-{[4-(2-fluorophenyl)piperazin- 1-ylJmethyl}-1H-benzimidazole ve 0-7[-(7-tetrophenyl)piperazinyl])1(myl)-11-benzimidazole ¢2-{[4-(2-nitrophenyl)piperazin -1-yljmethyl}-1H-benzimidazole 1-([;-(7-methoxyphenyl)piperazin {df ])1(imbidazole ¢2-{[4-(2-methoxyphenyl)piperazin-1-) ylJmethyl}-1H-benzimidazole 4-(111-benzimidazolyl)¥(methyl)piperazinyl(1)phenol ¢4-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1-yl]phenol Y. 7-(40-[7-methylthio)phenyl]piperazinyl {(V)menhil)-111-benz-imbidazole ¢2-({4-[2-methylthio)phenyl]piperazin-1-yl} methyl) -1H-benzimidazole (a SHY) 4[(-7phenyl)piperazinyl [(V)methyl)-171-benzimidazole ¢2-{[4-(2-ethoxyphenyl)piperazin-1-ylJmethyl }-1H-benzimidazole xe 111-41-7 benzimidazolyl (7) (da piperazinyl (1)]!FQOL ¢2-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1- yl]phenol ha

LY

Myl)-111-benzyimidazole](1)-(7-methoxyfutable)piperidinyl £1)¢2-{[4-(2-methoxyphenyl)piperidin-1-yljmethyl}-1 H-benzimidazole Impedazole ir HY[ie))1( piperidinyl (1)a) (pyridinyl ¢2-[(4-pyridin-2-ylpiperidin-1-yl)methyl}-1H-benzimidazole imidazole pH = f ie (HY) 1-linideribor hyde JET Yd 7?-[(;0¢2-[(4-phenyl-3,6-dihydropyridin-1(2H)-y)methyl]-1 H- benzimidazole (mgyl)-111-benzimidazole](1)(piperazinyl)(1)-(-methylpyridinyl) 11-7¢2-{[4-(6-methylpyridin-2-yl)piperazin-ylJmethyl }-1H-benzimidazole methyl]-111-benzoimidazole (1) piperazinyl (1)-methyl-4-pyridinyl 7 ([-7 ¢2-[(2-methyl-4-pyridin-) 2-ylpiperazin-1-yl)methyl]-I H-benzimidazole 2-{[(2S)-2-methyl-4-pyridin-2-ylpiperazin-1-yljmethyl}-1 H-benzimidazole methyl)-111-benzimidazole](1) piperazinyl (Y) 7 -([(87)-7-methyl-?;-pyridinyl ¢2-{[(2R)-2-methyl-4-pyridin-2-ylpipcrazin-1-yljmethyl}-1 H-benzimidazole pyridinyl)7 ({meshan])1(methyl)piperazetyl (Y)L-8-(4[1-7-(111-benzimidazolyl)ve

N-{2-(4-(1H-benzimidazol-2-ylmethyl)piperazin-1-yl]pyridin-3-a |catopamycin ¢tyl}methanesulfonamide methyl)-111-benzoimidazole [(1) Piperazinil ((Y)fluoropyridinyl-7(-4[(-7β) ester (le or ¢2-{[4-(3-fluoropyridin-2-yl)piperazin-1-ylJjmethyl} -1H-benzimidazole or a pharmaceutically acceptable prodrug thereof. amid amide “The present invention relates to a method for the treatment of asexuality >A) and in the embodiment of dyspareunia or vaginismus in females led to erectile dysfunction clitoris; painful congestion in the most distant human beings includes giving the purest of the said humans who are in need of 7-[(; ylpiperazin-1-yl)methyl]-1H- Js sad 3 ar HY methyl]- ((1a) or a pharmaceutically acceptable prodrug thereof. amide cester amide or salt; tbenzimidazole ester

0 In another embodiment, the present invention relates to a method for treating female anorgasmia and clitoral erectile dysfunction; vaginal engorgement; Dyspareunia or painful vaginismus in a human female involves giving the said human female in need of such treatment a Val Ladle amount of di(1(tartrate) 7-[(©-pyridethyl(7)piperazinil (0)methyl]-2) 111 -benz 2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1H-benzimidazole Sor ad .bis((L)tartrate) In another embodiment the present invention relates to a method for treating agitation female sex; erectile dysfunction og lad vaginal engorgement; dyspareunia or painful Jedd spasm in female humans includes administration of said human female in need of such treatment as a therapeutic decoction of 7-[(©-pyrimidinil) (1) piperazinil (0)methyl]-111-benzimidazole 2-[(4-pyrimidin-2-ylpiperazin-1-yl)methyl]-1H-benzimidazole or alkaline; ester amide Samide prodrug In an embodiment (oa) the present invention relates to a method for the treatment of female anorexia; clitoral erectile dysfunction; dyspareunia (led) engorgement or painful Jal 1 spasm in female humans involving the administration of said human analgesic Which need this treatment a therapeutic value of 7-41-(111-benzimidazolyl-(7)methyl)piperazinil [1](pyridinol 6-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1) -yljpyridin-3-ol (9) or salt; An ester amide or a pharmaceutically acceptable prodrug thereof. In an embodiment AT the present invention relates to a method for the treatment of #0 cardiovascular disorders, inflammatory disorders, attention deficit hyperactivity disorder, cAlzheimer's disease, Drug cab use Parkinson's disease Anxiety aanxiety Mood disorders 5 and depression Depression in humans includes giving said humans who are in need of this treatment a therapeutically effective amount of a compound In formula (1) or a salt; an amide ester or a pharmaceutically acceptable prodrug thereof.

In another embodiment; The present invention relates to a method for treating a variety of cardiovascular disorders; inflammatory disorders; attention deficit hyperactivity disorder; Alzheimer's disease; misuse of the drug; Parkinson's disease; anxiety; Mood disorders and depression in humans include giving said human beings who are in need of this treatment a therapeutic value of a compound of formula (1) where the said compound of formula (1) is from: Jha [1-7 pyridinyl] (1) Piperazinil [1]methyl-111-4-benzimidazole ¢2-{{4-(3-methylpyridin-2-yl)piperazin-1-yljmethyl}-1 H-benzimidazole 41-7 - (111-benzimidazol-lyl (din (TY)piperazinyl])1(nicotinotrile ¢2-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1-yl]nicotinonitrile 0.1 EY “0 bromo-1,7(-pyridinyl)(1(piperazinyl))(1)methyl]-111-benzoimidazole 7-dibromo-2-[(4-pyridin-2-ylpiperazin-1-yl) (methyl]-1H-benzimidazole,5?8-fluoro-1-7(“pyridinyl(Y)piperazinyl)(1)methyl]-111-benzimidazole [¢5-fluoro-2-[() 4-pyridin-2-ylpiperazin-1-yl)methyl]-1H-benzimidazole ae 1-4-7 #-thiazolyl 1(piperazinyl])1(methyl)-01-benzimidazole ¢2-{[4~(1,3-thiazol-2-yl)piperazin-1-yl]methyl}-1H-benzimidazole 1-7(-pyridinyl(Y)piperazinyl)(1) methyl]-111-benzimidazole-1-carboxylate ¢isobutyl 2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1H-benzimidazole-1 -carboxylate ier 8) (7 ) piperazinyl (0) methyl]-1-(pyrrolidinyl (1) carbonyl)-01- 7-benz imidazole 2-[(4-pyridin-2-ylpiperazin-1-ylymethyl]-1-(pyrrolidin-1-) ylcarbonyl)-1H- ¢benzimidazole die SENN 77(-pyridinyl(7)piperazinyl)(1(methyl]-111-benzimidazole-1-carbox_samide N,N-dimethyl-2-[ (4-pyridin-2-ylpiperazin-1-yl)methyl]-1H-benzimidazole-1- tcarboxamide ve 1-7( ylpiperazin (((V)methyl]-111-benzimidazole ¢ 2-[(4-phenylpiperazin-1-yl)methyl]-1H-benzimidazole YAYA

71 61-7 Benzimidazolyl (1(methyl)piperazinyl (1))]-benzonitrile ¢2-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1 -yl]benzonitrile 21- 7-(7-chlorophenyl)piperazin[(V)methyl)-111-ben-g imidazole ¢2-{[4-(2-chlorophenyl)piperazin-1-ylJmethyl}-1H-benzimidazole 0 41 -7-(7-fluorophenyl)piperazin[(V)methyl)-01-benzimidazole ¢2-{[4-(2-fluorophenyl)piperazin-1-ylJmethyl}-1H-benzimidazole 41-7 -(7-nitrophenyl)piperazin[(V)methyl)-171-benzimidazole ¢2-{[4-(2-nitrophenyl)piperazin-1-ylJmethyl}-1H-benzimidazole 1-7 -( 7-moxyphenyl)piperazinyl yom —{ da [(V)imidazole ¢2-{[4-(2-methoxyphenyl)piperazin-1-yljmethyl}-1H-benzimidazole \ 41-4 111(7-benz) imidazolyl (Y)methyl)dian(1)]phenol ¢4-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1-yl]phenol 7-((71-4-) Methylthio)phenyl]piperazin 1(methyl)-111-benzimidazole ¢2-({4-[2-methylthio)phenyl]piperazin-1-yl} methyl)- 1 H-benzimidazole 0 1-7-(7-ethoxyphenyl)piperazin])1(methyl)-111-benzimidazole ¢2-{[4-(2-ethoxyphenyl)piperazin-1-ylJmethyl}- 1H-benzimidazole 7 -[4-(111-benzimidazolyl-(fie(Y)piperazinyl) Jom[(V)¢2-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1-yl]phenol EY -(7-methoxyphenyl) en HY {fa [(V) Jin imidazole ¢2-{[4-(2-methoxyphenyl)piperidin-1-ylJmethyl} - |H-benzimidazole ~~ v- 1 -[(? -(pyridinyl {df))1( dirs (1) 111 benzimidazole ¢2-[(4-pyridin-2-ylpiperidin-1-yl)methyl]- 1H-benzimidazole 7-[(); - Phenyl-7” (SET HY) rubyridyl-1 (HY)methyl]-171-benz-imildazole ¢2-[(4-phenyl-3,6-dihydropyridin-1(2H)-yl)methyl]- 1H-benzimidazole vo 4-7 -(7-methylpyridinyl (?)) piperazinyl [(V)methyl)-111-benz Oa ¢2-{[4-(6-methylpyridin-2) -yl)piperazin-ylJmethyl}-1H-benzimidazole VATA

7 [(?-methyl-4-pyridetyl(1)piperazinyl [dia))1( 111 ben-g imidazole ¢2-[(2-methyl-4-pyridin-2-ylpiperazin-1 -yl)methyl] -l H-benzimidazole 11-7( 57)- 7-methyl- ;-pyridinyl (Y)piperazinyl 3H){0a[(V)imidazole [(2S)-2-methyl-4-pyridin -2-ylpiperazin- 1-ylJmethyl}-1H-benzimidazole {-£2 0 | 11-7(87)-7-mthel-?; -pyridinyl(Y)piperazinyl])1(methyl)-111-benz-impidazole £2-{[(2R)-2-methyl-4-pyridin-2-ylpiperazin-1 -ylJmethyl}-1H- benzimidazole 1 (-1-1-benzimidase and lyl (¥) methyl)](1) dome pyridinyl (7)({ methane N-{2-(4-(1H-benzimidazol-2-ylmethyl)piperazin -1-yljpyridin-3- a dbus ¢yl}methanesulfonamide 00 jl -(7-fluoropyridinyl (YF)piperazinyl])1(syl)-111-benzimibazole ¢2-{ [4-(3-Muoropyridin-2-yl)piperazin-1-yl]methyl}-1H-benzimidazole or its salt; an L-cester amide is a pharmaceutically acceptable prodrug thereof. In another embodiment the present invention relates to a method For the treatment of Ja disorder from cardiovascular disorders; inflammatory disorders; attention deficit hyperactivity disorder; Alzheimer's disease; drug misuse; Parkinson's disease; anxiety; mood and depression disorders in humans including administration of said subjects in need of such treatment as Val Therapeutic form of 4([1-7-pyridinyl)1(piperazinyl Hd))1(benzimidazole) ¢2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1H-benzimidazole or a salt; a cester amide or a pharmaceutically acceptable prodrug thereof. Tr and in an embodiment of AT the present invention relates to a method for treating a disorder selected from cardiovascular disorders; inflammatory disorders; attention deficit hyperactivity disorder AS al Alzheimer's disease; lial abuse Parkinson's disease; anxiety; Mood and anxiety disorders in humans include administration of said subjects in need of such treatment as a Val Ladle amount of di(1(tartrate) OY-pyridinyl(1)piperazinil(1)methyl]-1 Yo 1 benz 2-[(4-pyridin-2-ylpiperazin-1 -yl)methyl]-1H-benzimidazole Jota wad .bis((I)tartrate) VATA

L.A

In an embodiment of al the present invention relates to a method for treating a disorder selected from cardiovascular disorders; inflammatory disorders; attention deficit hyperactivity disorder; Alzheimer's disease; Misuse of the drug. Parkinson's disease; anxiety; Mood disorders and depression in humans including administration of the mentioned humans which is in the dala for this treatment © Val Ladle amount of 7-[(?;-pyrimidinyl(V)piperazinyl))1(methyl]-111-benz A generic imidazole derived from 111-6-[abra(Ag-amala-2-sansanum-4)]-2; or its salt; an amide ester or a pharmaceutically acceptable prodrug thereof.In another embodiment the present invention relates to a method For the treatment of a disorder selected from among the cardiovascular disorders; inflammatory disorders; attention deficit hyperactivity disorder; Alzheimer's disease; drug abuse; Parkinson's disease; anxiety; mood and depression disorders in humans including administration of said persons in need of such treatment as much as Val Therapeutic form of 41-76-(111-benzimidazolyl-(7)methyl)piperazinyl])1(pyridinol) 6-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1-yl}pyridin-3-ol (Y') or ester jad “le amide or a pharmaceutically acceptable prodrug thereof. In another embodiment the present invention relates to compounds of the formula (1): A M Ra “Yr Nr NR Re rN Ro E (11) or salt; cester amide or a pharmaceutically acceptable prodrug thereof, where: M JA To from: YAYA

£3 Ra Ra 1 b - 1 Ry Ra Ry R2 NO 1 2 } Ry gh ONT solution for ke, Rs R2 — for 27 I “= 2 R I I oa a Ry l | R: I M Rs Y A 2 Layth Al-War NTR De Lo L Hirt es ! Ma Nah By B and "Labad ° * choose from NH© or iS 1 emits a selection of ¢CH,CH,CH,CH, 3 CH,CH,CH, «CH,CH, «CH, with each of the yls Rs Ry and each separately selected from the alkoxy hydrogen chydrogen pumla Alkenyl Alkyl Calkyl J Calkylsulfinyl Ji 5S Calkylsulfonyl Sulfonyl Alkyl Fe Calkylthio Alkenyl Calkynyl Alkoxycarbonyl Vo Alkyl Carbonyl Calkylcarbonyl Alkyl Carbonyloxy Calkylcarbonyloxy ccarboxy Cyano ccyano formyl halogen <haloalkoxy haloalkyl hydroxy chydroxy hydroxyalkyl mercapto nitro: NZ, Z, nitro or carbonyl (NZ,Z,)carbonyl (NZ,Z,) where 87,57 is selected separately from the group consisting of an alkyl chydrogen Vo calkylcarbonyl alkylsutfonyl or formyl formyl Re Ra «Ry and BS Rp each separately from alkoxy hydrogen alkenyl alkyl calkyl alkylsulfinyl Ji calkylsulfinyl sulfonyl calkylsulfonyl alkyl calkylthio of alkynyl alkoxycarbonyl J carbonyl calkylcarbonyl calkylcarbonyloxy carboxy VATA |

cyano “cyano formyl halogen chaloalkoxy halo alkyl chaloalkyl hydroxy chydroxyalkyl J— <i Merquite cmercapto Nichoro -NZ\Z; “nitro or carbonyl ¢(NZ,Z;)carbonyl (NZ,Zs) J EN Rg from hydrogen chydrogen alkoxycarbonyl Ji calkoxycarbonyl alkyl ° alkyl calkylcarbonyl Jorge S aryl carbonyl Jf carylcarbonyl cycloalkylcarbonyl heterocycle carbonyl heterocyclecarbonyl or carbonyl (NZ,2,) tot (17,22)?; And Jus Re is from the phase consisting of hydrogen or an alkyl calkyl, provided that A Lexie represents X 3 and > B 2 i CHa a calm wound. 1 no > 5 Xs representing WS a or R; representing a moiety other than hydrogen and in an embodiment of “al” the present invention relates to compounds of formula (I) where Rp is less than Re And m 8 (JS JUS TO) separately from hydrogen or halogen Re thalogen representing hydrogen and gene 'hydrogen 1 ES: A Ra and p s Pi A: el 56 70 NT RO Y and Ry as defined in formula (1) and in the embodiment of al ¢ 1 of the present J 2 select relates to compounds of formula 00) where “Rg” is Ra Re and and 8 JS choose separately from hydrogen of hydrogen halogen Rr 5 Rg ¢halogen each representing hydrogen ¢CH, Jia L hydrogen M representing YAYA

b N pl. . NE R4 hydrogen and some each representing hydrogen Ry Ry 56 77 (I) and in another embodiment; The present invention relates to compounds of the formula Bra Rs —~ Ry

N

Ra a 3

Re Ae N NN ) 0 the Re 1

Rp Re (1m) where: Alaa or an acceptable prodrug thereof (amide Aud) cester or salt; Ester 8 Rs Ry Ry and Ba are selected separately from the group consisting of hydrogen <hydrogen alkyl capretinyl Ji calkylsulfinyl sulfonyl catkylsulfonyl alkyll sulfonyl amino BEEN calkylsulfonylamino in alkylthio or hydroxy A is chosen from the set consisting of sf CHCH,CH, «CH,CH, «CH; Rpg Re «Rp «Ra 01 are each selected separately from the group consisting of alkoxy hydrogen calkyl J calkenyl alkyl sulfite calkylsulfinyl Ji calkylsulfonyl kip ritonyl alkyl Vi calkylthio alkynyl calkoxycarbonyl alkyl carbonyl calkylcarbonyl alkyl carbonyloxy carboxy cyano formyl 'halogen halo alkoxy hydroxyalkyl hydroxy hydroxy haloalkyl BERS chaloalkoxy Vo dus or carbonyl (22) of the 117,72(08:0) -NZ,Z, enro of ¢mercapto alkyl hydrogen is selected separately from 7' formyl or formyl alkylsulfonyl calkylcarbonyl cr butyl Ji YAYA oy alkoxycarbonyl chydrogen is selected from the group consisting of hydrogen Rg carylcarbonyl aryl calkylcarbonyl carbonyl Ji calkyl alkoxycarbonyl heterocyclic carbonyl ceycloalkylearbonyl cyclic carbonyl J and $(NZ,Zy)carbonyl (NZ,2,) or heterocyclecarbonyl alkyl carbonyl or alkyl hydrogen some is chosen from the group consisting of hydrogen 0 (Ry represents at least one hydrogen of hydrogen Re provided that when it represents

Jydrogen other than hydrogen WER, or Ry with less (Ry where: after (IT) and in another embodiment the present invention relates to compounds of the formula provided that it is hydroxy or hydroxyhydrogen separately from hydrogen JS HES TAR, PA W

Rp and Re “Rp” Ra thydroxy or p-hydroxy Ry Ry (Ry representing at least one of 01 representing hydrogen Re thalogen or halogen hydrogen separately from hydrogen JC ja TS (I) defined in the formula WSL thydrogen and Ry Ry and in another embodiment the present invention relates to compounds of the formula ([11]) where

Jas L thydroxy Jie is thydrogen B each separately represents hydrogen or halogen hydrogen separately from JS hydrogen and what is selected Re Re Ry (CH 0 hydrogen each represents hydrogen Re and Rg and halogen

Ry sR; Where (I) and in another embodiment the present invention relates to compounds of formula

Rp s Re Rg L ¢ hydrogen separately represents hydrogen JS B and some represent hydrogen Re thalogen or halogen hydrogen each separately selected from alkyl hydrogen Rp and ¢hydrogen 0 (Ry Whereas (II) and in another embodiment, the present invention relates to compounds of formula or alkylsulfonylaminohydrogen a and b8 each selected separately from hydrogen alkyl or alkyl Ry Ry provided that they represent one over The least of the alkylsulfonylaminos are chosen separately from Rpg Re Rp Alolalah? methyl sulfonyl amino sil captonyl and what is known as ¢thydrogen representing hydrogen Rp thalogen or halogen hydrogen Yo (U1 ) in the formula oY b and Ry electrolytes The present invention relates to compounds of formula (11) where AT and in an embodiment the alkyl sulfonylaminos Ry separately represents hydrogen 0:0860 t; JS b represents Separately from hydrogen JS Jaa Rp and Re «Rg »Ra ¢CH, representing L talkylsulfonylamino hydrogen (p>58 each representing Rp, Rg, and ¢thalogen or halogen hydrogen (IV) and in another embodiment the present invention relates to compounds of the formula

A

Ra 7

Re N N N N 3

Cy TR

R ZN

¢R

Rp E (v) where: Alaa or an acceptable prodrug thereof is an amide cester or salt; Esther chooses from: A

R 8 8 B R “2 S “2 8 Ra 1 | 2 5 2 5 B ny Rs \ N Ny” 3 ™ = 3 J R by A R 5 PE Rs J = A = T 4 70 X 3 ¢ 0' 0 p N Ry ¢ 7h N Ry, Rs ye by Ry view Ry Re

Rigo \ NN tl 5 8 Te 0 for aa

Tha VX Wap ba game

CNS TR Rs SN 3 Rs 0 Rs

RixNR

Ry Ra A X N R 2

X —N LN Ne . I N ja L mr ab cel 3 = ' 5 b( ¢ x; SN ¢ BS N 3 4 Rs ¢ Rs ' 2 N x—N

R R

A N : N A x I 4 ¢ Sw Hkd aaa or Rs | wy Rs ¢S or 0 “(NH) from oes X

YAYA of ¢CH,CH,CH,CH, § CH,CH,CH, «CH,CH, «CH, of Ji Ba are selected separately from the group consisting of R55 Ry Rs nickel J calkylsulfonyl alkyl sulfonyl alkoxy catkylcarbonyl alkyl carbonyl calkoxyearbonyl carbonyl SS ° chalogen halogen “formyl formyl ccyano ciato carboxy carboxy calkylearbonyloxy chydroxy hydroxy chaloalkyl halo alkyl chaloalkoxy ((NZ,Z,)carbonyl (NZ,2,) or carbonyl NZ,Z, “nitro nitro ¢mercapto alkyl hydrogen; mercapto alkyl chydrogen where 2, and :2 are selected separately from the group consisting of ¢ hydrogen formyl or formyl alkylsulfonyl <alkylearbonyl alkyl carbonyl calkyl ve and with each selected separately from the group consisting of hydrogens Re «Rs Ra calkylsulfinyl alkyl sulfonyles calkyl alkyl calkenyl Jani calkoxy alkoxy hydrogen alkylcarbonyl calkylthio alkyl shio calkylsulfonyl alkylcarbonyloxy calkylcarbonyl alkoxycarbonyl chalogen (p> sila formyl formyl ccyano carboxy Ve hydroxyalkyl chydroxy chaloalkyl chaloalkoxy ¢ (NZ,Zy)carbonyl (NZ,2,) or carbonyl NZ,Z, «nitro cmercapto 2S ye alkoxycarbonyl chydrogen is chosen from the group consisting of hydrogen Re carylcarbonyl aryl kryothyl calkylcarbonyl alkyl carbonyl calkyl alkyl alkoxycarbonyl heterocyclic carbonyl coycloalkylearbonyl alkyl cyclocarbonyl |» ¢(NZ,Z;)carbonyl ( NZ,Z,) or a heterocyclecarbonyl talkyl carbonyl or an alkyl hydrogen chosen from the group consisting of hydrogen Re

SCH from © or Juan' 27 7 and not present when carbon carbon atom 7 Jia bond === present when

CH stands for vo

YAYA

In another embodiment, the present invention relates to compounds of formula (IV) where Ry (Ry Rp 5 Re JS selects separately from hydrogen or Jia Rg thalogen Z hydrogen represents “ CH bond ———— does not exist; Jas A Rp m x hd Rs ?; and Na Ry Ry Ry b] and Rs as defined by formula (IV ) ° In the embodiment of al ¢ the present proposal relates to compounds of the formula Rp «Ra Cua (1v) Re and Rp is selected from hydrogen or halogens Re thalogen and Ry is JS of them (J separately hydrogen CH, Jia L hydrogen 2 represents “CH” bond ==—— not present; A represents Ra Ri SL AR, Rs ? Ry (Ry and Ry each represent hydrogen and Ry and Rs as defined by Ve in formula (1v) and in another embodiment the present invention relates to compounds of formula (IV) Where Rg Ry m and who (IS) choose separately from hydrogen or halogen Jie Rg thalogen hydrogen Z thydrogen represents «CH bond ---- non-quality; M Alia J 2 er mogo 2 Ra R, ry" Rb x Ni Fa A; Ba Ry Ry Ry and B' as defined in the form (IV) eo and in other embodiments; The present invention relates to compounds of formula (IV) where M M and M 8 Jas PO each belong to hydrogen or a halogen Rr 5 Re ¢ halogen each representing Z “CH, Jie L hydrogen” “CH” represents the bond ---- does not exist? A overloads YAYA

and Ri TY Rj NY 2 . . :; Rs Ry and Ry (JS separately represents hydrogen thydrogen and Ri as defined in formula (Iv) and in another embodiment; the present invention relates to compounds of formula (IV) where Re Rg (Ra and 16 JS JESS hydrogen halogen Je Re thalogen hydrogen Z hydrogen 2 represents ¢C bond -<--- present; m represents and Riv A Ra x Ry “Ry Ry” Ry Lt Rs and Ry as defined in formula (IV) and in another embodiment the present invention relates to compounds of formula (IV) where Ry Ry Re and M8 Bs TY separately from hydrogen or halogen y and with (JS of them represents hydrogen L thydrogen represents Z (CH), representing ©; bond == 50 A 535 a 0 represents and Rie ARs x Rs; Ry “Ry and Ry each represent hydrogen thydrogen and Rs sR; as defined in formula (IV) Definitions In accordance with the present invention, the following terms have the meanings ascribed to them as used throughout this specification and the appended claims: The term “alkenyl” as used herein; refers to a straight or branched-chain hydrocarbon containing ? to 01 carbon atoms and contains at least one carbon-carbon double bond (oy calkenyl JS). -17 cethenyl to name a few; Ethinyl «4-pentenyl -pentyl-6 (3-butenyl -butenyl 2-methyl-2-propenyl 7-propyl 2-methyl-1- -heptyl 1--lethem-7 » 2-heptenyl (5-16); Attached to the main molecular moiety by an (old) atom, as I know in this alkyl alkyl. Examples include alkoxy (: ah; but not limited to oxygen 2-propoxy? - propoxy ¢propoxy (S525 cethoxy emethoxy pentyloxy ¢ tert-butoxy cbutoxy 0.1 -hexyloxy to cold! As used in this " alkoxyalkoxy The term “alkoxy” denotes an alkoxy attached to the main molecular moiety (old) as defined herein calkoxy by another alkoxy group; as defined herein. Includes but not limited to alkoxy by the alkoxy group calkoxyalkoxy ALAN ae 2-ethoxyethoxy 7-ethoxy ctert-butoxymethoxy .methoxymethoxy and 2-methoxyethoxy ethoxy as used in this statement To ("alkoxyalkyl alkyl SSI") and the term refers to attached to the main molecular moiety lll as defined in this alkoxy group of alkoxy, as defined in this statement. Alkyl methylation by alkyl group 0 includes but is not limited to; T-butoxymethyl calkoxyalkyl on the alkyl 2-methoxyethyl Jl 7-methoxy 2-ethoxyethyl ethyl Y abta honey “m-methoxymethyl Jie and cobalt as used in this” alkoxycarbonyl The term refers to "the alkoxycarbonyl attached to the main molecular moiety (lal) as defined in this alkoxy SS (ve group on Aba) as defined in this book. They include carbonyl Jus S by the group mkah oA mitoxy yaa ally, for example, alkoxycarbonyl alkoxycarbonyl -butoxycarbonyl ethoxycarbonyl emethoxycarbonyl carbonyl .tert-butoxycarbonyl As used in Calkoxycarbonylalkyl, the term “alkoxycarbonyl alkyl” as defined in this statement calkoxycarbonyl refers to an alkoxycarbonyl group ° as defined in this alkyl linked to the main molecular moiety by an alkyl group, for example The example is calkoxycarbonylalkyl in the statement. Examples of alkyl alkyl carbonyls include but not limited to - 4 3-methoxycarbonylpropyl; 4-ethoxycarbonylbutyl (15 su) as used in this statement “alkoxysulfonyl sulfonyl mS SI” The term 01 oad attached to the loll moiety (as calkoxy is defined herein) refers to the alkoxy group as Identified in this statement Examples of the principal sulfonyl by a sulfonyl group include but are not limited to calkoxysulfonyl sulfonyl SS on and ethoxysulfonyl emethoxysulfonyl .propoxysulfony! Vo refers to a coll hydrocarbon as used in this alkyl and the term refers to an alkyl and carbon includes carbon atoms 01 to 1 straight or branched chain containing hydrocarbon p- ethyl Examples of Alkyl and, for example, but not limited to, methyl ter ethyl p<kyotyl or th-butyl anamhi dso-propyl isopropyl n-propyl propyl isopentyl isopentyl + n-pentyl p-pentyl ctert-butyl Jf smh isobutyl isobutyl ve methyl SEY 7 3-methylhexyl lithem-1 n-hexyl p-hexyl neopentyl cn-heptyl p-heptyl 2 3-dimethylpentyl methyl Pentyl AUT T 2,2-dimethylpentyl Jib n-decyl p-decyl n-nonyl n-octyl p- ethyl as used in this statement to Calkylearbonyl carbonyl Js" term Huds attached to the main molecular moiety lad as defined in this alkyl group vo as defined in this statement. Examples include a carbonyl alkyl with a carbonyl group

YAYA

The carbonyl calkylearbonyl to name but a few is acetyl cacetyl 1-oxopropyl 1 “l-oxopropyl 7-dimethyl-1-oxopropyl rum0:m1-1-0*0a2,2-4002” 1 1-oxopentyl Jai and Sca-1, 1-oxobutyl The term JS denotes the calkylearbonylalkyl alkyl carbonyl as used in this statement; to the alkylearbonyl alkyl carbonyl group, as defined in this statement. Examples of Ji calkylcarbonylalkyl include but are not limited to 7-oxopropyl 2-ox0propyl 7 0-dimethyl- 7-oxopropyl 3-dimethyl-2- 3 coxopropyl '- 3-oxobutyl and 7-oxopentyl 3-oxopentyl 01 The term J carbonyloxy (“alkylcarbonyloxy” as used herein” refers to the calkylearbonyl alkyl group as defined herein Linked to the main molecular moiety by an oxygen atom, and the moieties include J lh calkylearbonyloxy, but not limited to cacetyloxy, cethylearbonyloxy, and tert-butyl carbonyloxy, tert-butylcarbonyloxy, Ve. The term “calkylsulfiny [as used herein]” refers to the dally alkyl group as defined herein. Linked to the main molecular moiety by the storied sulfonyl group as used herein. Examples of alkylsulfinyls include calkylsulfinyl For example, but not limited to Jil 5 methylsulfinyl sulfinyl -ethylsulfinyl Ye and the term “Calkylsulfonyl as used in this statement refers to the alkyl group dalkyl as defined in this (lll) attached to the molecular moiety The principal is by the csulfonyl sulfonyl group as defined in this statement. The amalgams for Ji include but are not limited to the alkylsulfonyl sulfonyl in dau; methylsulfonyl and ethylsulfonyl -Yo The term “calkylsulfonylamino as used herein” refers to the calkylsulfonyl alkyl group as defined herein.” Related to YAYA

with the major molecular moiety by the NH group. Examples of alkyl sulfonylaminos include, but are not limited to; methylsulfonylamino ethylsulfonylamino . The term “alkylthio as used herein” refers to the alkyl group J. as defined herein (lal) attached to the main molecular moiety by An atom of sulfur sulfur Examples include Jf Shio alkylthio for example but are not limited to methyl sulfani emethylsulfanyl ethyl sulfur cethylsulfanyl heth -butyl sulfyl tert-butylsulfanyl hexyl sulfyl -hexylsulfanyl The term "alkyl" indicates Calkylthioalky! as used in this statement 0 to the calkylthio group as defined herein” linked to the main molecular moiety by the alkyl group as defined herein. BAY includes but is not limited to J 58 alkyl thioalkyl; Y 5 ¢methylsulfanylmethyl -(ethylsulfany) alkyl .2-(ethylsulfanyDethyl) The term “alkynyl” as used in this statement refers to a straight or branched-chain hydrocarbon containing ? to 01 carbon atoms and contains at least one carbon-carbon triple bond Examples of calkynyls include but are not limited to cacetylenyl 1 propynyl ¢l -propynyl 7-propynyl 2-propynyl 7-butynyl q = Y pentynyl 2-pentynyl and su) 2-I-butynyl and the term "caryl" as used herein Statement; to a monocyclic system or a rede-cyclic system of two or three rings in which one or more of the fused rings is aromatic. Examples of aryl enra include; For example, no ma al anther 2111180601 azolinyl al-Bamsalija fluorenyl cindanyl Judai <fluorenyl indenyl naphthyl phenyl and tetrahydronaphthyl Yo. and can carry Aryl groups according to this invention from 1 to © Ja a substituents separately from calkenyl calkoxyalkoxy

alkoxyalkyl “alkoxycarbonyl” alkoxycarbonyl alkyl calkoxycarbonylalkyl alkoxycarbonylalkyl alkyl J calkoxysulfonyl alkyl carbonyl Ji calkylcarbonyl Ji calkylcarbonylalkyl carbon eS sh calkylearbonyloxy alkyl shio cal kylthio alkyl thioalkyl calkylthioalkyl alkynyl ° arsol; carboxy carboxy ccarboxyalkyl JS cyano ceyano cyanoalkyl ccyanoalkyl ethylene dioxy cethylenedioxy formyl halo alkoxy chaloalkoxy halo haloalkyl Jif halogen 181080 hydroxy hydroxy alkyl hydroxyalkyl mercapto ¢mercapto ¢methylenedioxy NZ,Z, “nitro D77 and (NZ Zy)carbonyl (NZ,Z,) si y the term “Carylcarbonyl” as used in this statement; To an aryl group as defined in this lll attached to the main molecular moiety by de sans carbonyl carbonyl as defined in this statement J fal Aad includes carylcarbonyl for example but not limited to benzoyl benzoyl and -naphthoyl (the term 'Coarbonyl' as used herein refers to the C0 group) and the term 'Cearboxy' as used herein refers to the -CO.H group The term “Cearboxyalkyl as used herein” refers to a carboxy group as defined herein” linked to the main molecular moiety “by means of an alkyl group as defined herein. ALAN includes but is not limited to ccarboxyalkyl JS carboxymethyl-1-carboxymethyl, 2-carboxyethyl and 7-carboxypropyl. used in this statement” refers to the CN group and the term “cyanoalkyl alumina” is used in this statement; It is also used in this statement to refer to the group ve cyano as defined in this statement; bound to the main moiety by a Ji group first; As defined in this statement. LAY includes the coyanoalkyl alkyl giles YAY A

For example, but not limited to; $Y ccyanomethyl Jie sila 2-cyanoethyl alkyl and ~Y cyanopropyl: 3-cyanopropyl The term “Ceyeloalkyl” as used in this statement refers to a cyclic hydrocarbon group Saturated containing from ? to 8 carbon atoms ° carbon ° Examples of cycloalkyl include cycloalkyl cyclopropyl cyclobutyl ji ceyclobutyl cyclopentyl cyclohexyl cycloheptyl and cycloacetyl .cyclooctyl The term JS cycloalkylearbonyl as used herein refers to a cycloalkyl group as defined herein bound to the 01 main molecular moiety by a carbonyl group as defined herein Examples of alkyl cyclocarbonyl include, but are not limited to, cyclopropylcarbonyl cyclobutyicarbony! This is (Om - to -0(0110(.0) group. Where the oxygen atoms in the ethylenedioxy group are linked to the main molecular moiety by one carbon atom forming a five-membered ring or the oxygen atoms are linked Ae sana oxygen ethylenedioxy is attached to the main moiety by means of two adjacent carbon atoms forming a six-membered ring. Ye The term 'formyl' as used herein; denotes the -0(0(11) group. The term 'halo' or 'halogen' as used herein denotes ~F sl -1 8+ «Cl and the term “haloalkoxy nS SY as used herein” denotes at least one halogen atom, as defined herein” bound to the main al ve moiety by Ae gene alkoxy as defined in this statement Examples of chaloalkoxy include but are not limited to 7-fluoro-1-chloroethoxy YAYA

«2-fluoroethoxy 7-fluoroethoxy» chloromethoxy chloromethoxy «2-fluoro-1-chloroethoxy

trifluoromethoxy and pentafluoroethoxy. The term “haloalkyl (as used herein”) refers to at least one halogen atom (LS) defined in this glad) bound to the moiety JERR 0 principal by the alkyl group as defined in this statement Examples of chaloalkyl J include but are not limited to chloromethyl ?-fluoroyl-2 HL fluoroethyl fluoromethyl ctrifluoromethyl Pentafluoroethyl and —Y

.2-chloro-3-fluoropentyl littenborolf-1-chloro

The term “heterocycle” denotes heterocyclic dl 0 as used in this statement; into a single, dual or triple loop system. Of the ALA monocyclic systems, which ring does it have? or; Organisms containing a heteroatom of nitrogen oxygen (pss coxygen or ssulfur or a ring with ©; 1 or a members containing an atom; two or three heteroatoms where laa tn the heterotoms are each separately from nitrogen cnitrogen oxygen and sulfur The five-membered ve ring contains one to two double bonds or may not contain it The six-membered and seven-membered ring may or may not contain one to three double bonds Examples of monocyclic systems include eg but not limited to azetidinyl cazetidinyl cazepanyl aziridinyl caziridinyl diazepinyl 1 “diazepinyl ?-dioxolanyl 3-dioxolanyl 1” dioxyl stack M:L dithianyl phosyl furyl 7-cimidazolyl cimidazolinyl cimidazolidinyl cimidazolidinyl 01201 and linyl isothiazolinyl cisothiazolidiny cisoxazolyl cisoxazoliny! and cisoxazolidinyl cisoxazolidinyl morpholinyl coxadiazolyl coxadiazolinyl coxazolidinyl coxazolyl Jig jb SI coxadiazolidinyl coxazolinyl ye coxazolidinyl piperazinyl cold Piperidinyl cpyranyl Jad sm epiperidiny!

Tt ¢pyridazinyl epyrimidinyl opyridinyl piperidinyl cpyrazolidinyl tetrahydrofuranyl pyrrolidinyl pyrrolidinyl ¢pyrrolinyl pyrrolinyl cpyrrolyl tetrazolyl ctetrazinyl tetrazinyl ctetrahydrothienyl tetrahydrothienyl cte trahydrofuranyl cthiazolyl Thiazolidinyl thiadiazolidinyl cthiadiazolinyl ctetrazolyl thiomorpholinyl cthienyl Jodi cthiazolidinyl thiazolidinyl cthiazolinyl Jd 5 jl ° 1,1- thiomorpholinyl oxide EY 1 cthiomorpholinyl triazolinyl cthiopy ranyl J—Hu of cdioxidothiomorpholinyl (thiomorpholine sulfone) Examples of binary cyclic systems include thiayl trithianyl hs triazolyl ctriazinyl triazolyl as the aryl ring Any monocyclic system of the above systems combined with an aryl group as defined in this statement or cycloalkyl I know this statement. Cycloalkyl group 0 for example is not ala another monocyclic system. Examples of di-systems include cbenzodioxinyl benzodioxinyl exclusive cbenzimidazolyl imidazolyl benzoxazolyl cbenzotriazolyl benzothiazolyl cbenzothienyl benzothiazolyl benzothioratel ebenzopyranyl benzoiratyl cbenzofuranyl benzofuratyl ¢<benzoxazolyl di-7 17 Andazolyl 1 : 002201 Indolyl Ala 000 » ccinnolinyl cbenzothiopyranyl Vo cnaphthyridinyl naphthyridinyl cindolizinyl indolizinyl ¢2,3-dihydroindolyl Jalsa 5 08 cisoindolyl ¢isobenzothienyl cisobenzofuranyl isobenzofuranyl «pyranopyridinyl quinolinyl quinolizinyl quinolinyl < quinolinyl tetrahydroisoquinolinyl ctetrahydroisoquinolinyl tetrahydroisoquinolinyl 'quinazolinyl A Systems A Ad and thioper inopyridinyl 0 k / rm 77800 m 010. The three-cyclic tetrahydroquinolinyl includes any two-ring system of the aforementioned systems combined with a group, as defined in cycloalkyl Als alkyl de gana, as defined in this statement”; aryl aryl For example, no dil or single-loop system. Examples of cyclic systems include (cold) this benzo[b;SD ccarbolinyl carbazolyl carbazolyl cacridinyl acridinyl yaa Yeo naphtho[7?-dibenzo[b,d]thienyl benzo[b; 3[thinyl AU cdibenzo[b,d]furanyl furyl [2 H]

+ b] furan cnaphtho[2,3-b}furan naphtho [7 «naphtho|2,3-b]thienyl Ji [mY cphenazinyl cphenothiazinyl phenoxazinyl <phenoxazinyl cthianthrenyl The heterocycles of this invention can carry Soa or two or three ja Zo substituents each separately of a calkenyl alkoxy alkoxy alkoxy B Al-Durr alkoxyalkyl alkoxycarbonyl alkoxycarbonylalkyl alkoxycarbonylalkyl alkyl J <i calkoxysulfonyl alkylcarbutyl calkylearbony! calkylcarbonyloxy alkyl in calkylthio alkyl thio calkylthioalkyl JX] Ve calkynyl carboxy carboxy alkyl ccarboxyalkyl cyano cyanoalkyl ceyanoalkyl ethylenedioxy formyl Haloalkoxy <haloalkoxy haloalkyl chaloalkyl halogen 0 hydroxy chydroxy hydroxy chydroxyalkyl Ji mercapto 10m0608» emethylenedioxy wait for man xo NZ Z, coxo and carbonyl (NZ, Z)carbonyl (NZ ,Z,) Ve and the term "¢" carbonyl heterocycle as used in this statement; into a heterocycle; As defined in this (oll linked to the main al moiety by a cearbonyl carbonyl group as defined in this statement. ABV includes a cheterocyclecarbonyl heterocyclic ring, for example but not limited to Jann yu ) 7) pyridin-3-ylcarbonyl carbonyl and quinolinyl (7) cr.quinolin-3-ylcarbonyl Jus: 7 The term 'hydroxy' as used in this statement refers to a - -OH group and the term 'hydroxy' An alkyl, Chydroxyalkyl as used herein, to at least one hydroxy group, as defined herein, is attached to the main molecular moiety by a nucleophilic alkyl group, as defined herein. Examples include ve on hydroxyalkyl BER To name a few; hydroxymethyl 7-hydroxyyl “2-hydroxyethyl 7-hydroxyproyl” YAYA

3-hydroxypropyl ?-ele-? -hydroxyheptyl 2-ethyl-4-hydroxyheptyl 7 4 -dihydroxybutyl .2,4-dihydroxybutyl The term de sand' protective hydroxy 704 or "protective group for ©" refers to a substituent protecting hydroxyl groups hydroxyl is one of the undesirable reactions during the 0 synthesis procedure. Examples of hydroxy protective groups include but are not limited to; Compounds of methyl ethers bearing substituents (aS sie Jie) methyl cmethoxymethyl “benzyloxymethyl! (trimethylsilyl)-ethoxymethyl « benzyl DG benzyl phenylttriphenylmethyl tetrahydropyranyl EC ¢tetrahydropyranyl ethers 01 ethyl ethers bearing substituents; for example 7-trichloroyl-2,2 2, trichloroethyl and butyl ¢t-butyl silyl ethers eg (oh Jie trimethylsilyl silyl t-butyldimethylsilyl and th-butyl dimethylsilyl) Phenyl glycin RA 1M00010; acetals and cyclic ketals, for example, two methyl acetal Jue ub P0A/A06” acetonide 06 and benzylidene acetal 1 cyelic ortho esters, for example Example: Methoxymethylene Adanata 6110 «7006; cyclic carbonates and cyclic boronates. The term 'mercapto' as used in this statement refers to the SH group and the term 'methylenedioxy' Also used in this statement is a to -OCH,0- group, where the two oxygen atoms 00 in methylenedioxy are linked to the main al moiety by two adjacent carbon atoms. The term “5 nitro as used herein” denotes a group of NOs and the term Ae pend’ refers to protective nitrogen 106860 as used herein; to those groups intended to protect amino group 0100 from undesirable reactions ve during the synthesis procedure. The nitrogen protective groups include 5m carbamate amides, “N-benzyl derivatives x yu N” and imine derivatives, YAYA.

Ty benzoyl acetyl “preferred is acetyl nitrogen and protective groups for terogenesis formyl formyl cbenzyloxycarbonyl (Cbz) (Cbz) benzyl benzyl (Boc) ter-butoxycarbonyl “pivaloyl” bivaloyl cphenylsulfonyl phenylsulfonyl perfluoroacetyl oh «tert-butylacetyl nt-butylacetyl ctert-butoxycarbonyl (Boc) .triphenylmethy! (trityl) phenylmethyl (triyl) hs trifluoroacetyl °

The term “NZ ZL as used in this statement” denotes two groups, 7 and 7

bound to the main molecular moiety by a nitrogen atom «010088. Each of 7 and 7. is selected separately from the nucleation alkyl chydrogen; Alkyl carbonyl calkylcarbonyl alkylsulfonyl Ji su pS and formyl and examples include 307,7 for example

“dimethylamino dimethylamino ¢methylamino methylamino camino to name a few; amino ve and (methylsulfonyl) amino (acetyl)(methyl)amino (acetyl) (methyl) amino cacetylamino amino Ji (methylsulfonyl)amino amino

The term carbonyl (:2,2) (NZ, Z;)carbonyl as used in this statement

to the group .002,7 as defined in this statement; linked to the main molecular moiety by

No carbonyl group 00: e; As defined in this statement. A Bal includes a carbonyl

(12:2) 047,2:(8:0071)”_ to name but not limited to the caminocarbonyl

(methylamino)cryothyl “(methylamino)carbonyl (t-methylamino) carbonyl

(((acetyl)(methyl)amino)carbonyl (((acetyl) (methyl)amino) carbonyl “(dimethylamino)carbonyl .(ethylmethylamino)carbonyl amino) carbutyl Jie and (ethyl)

9 The term “(2,12D) sulfonyl NO:2,042(50150”), as used herein, refers to a 2,02,02 group as defined herein; bound to the main molecular moiety by the en0ad sulfonyl group as defined herein. Examples of (212.25)a(212.25)sulfonylu: (2,042;042;aminosulfonyl(methylamino)sulfony!

J gS (dl (misl) (di) «(dimethylamino)sulfonyl Yeo .(ethylmethylamino)sulfonyl amino) Je and (ethyl ((acetyl)(methyl)amino)sulfonyl

‎YAYA

TA

= 0 as used in this statement” refers to the Coxe moiety, the term “exo” and the term “sulphritinyl-rman?”; as used in this statement refers to the -5(0)- group. The statement refers to the sulfonyl group Ja su pS and the term -f(5)0-. ° and the term “sexual dysfunction” as used in this statement “refers to the impairment of sexual function in mammals, including Sexual function in human males and females. The term “male sexual dysfunction” as used in this statement” refers to erectile dysfunction and premature ejaculation in males. The term refers to “female sexual dysfunction”; as used in This statement; to ye Vaginal congestion » Dyspareunia os kdl Erectile dysfunction (LLY) Lack of orgasm at . And painful vaginismus stereoisomers The compounds according to the present invention may exist in the form of stereoisomers or non-stereotypes. And these stereogroups are "m" RELY, where there are centers on a compound that deflects (Ju) "58" (indicating a compound that deflects light clockwise) and ve carbon deflects light in a counterclockwise direction) based on the order Substitutions around the chirality of the carbon atom. The terms “8” and “5” used herein are forms defined [IUPAC 1974 Recommendations for Section E, Fundamental Stereochemistry, op. The present invention includes different stereogroups Pure Appl. Chem, 1976, 45: 13-0 Special within the scope of this invention. It includes the stereogroups dsl and their mixtures, which are included 7 and mixtures of stereoisomers or stereoisomers. Diastereomers and stereoisomers are stereoisomers. Independent stereogroups of the compounds of the present invention can be prepared synthetically from commercially available raw materials containing asymmetric or occlusal centers or by preparing mixtures for those who are skilled in the technique. Tam is represented by a well-known racemic mixturs, a racemic dispersal process, that binds the mixture of abideans with an adjuvant that is non-collision; Separation of the mixture of elements (1) These differentiation methods in ve and liberation of the chromatography product or recrystallization of the resulting stereoisomer recrystallization

YAYA

Optically purified from the adjuvant or (?) direct separation of the optical enantiomers mixture on chiral chromatographic columns ably. The preferred compounds of the present invention include: 77 -(7-methylpyridinyl) (1) (piperazinil]) 1(methyl)-111-benzimbladazole ¢2-{[4-(3-methylpyridin-2-yl)piperazin-1 -ylJmethyl}-1H-benzimidazole e 41-7 -(111-benz (Y) ) dl Jed methyl)piperazinil](1) nicotinotrile ¢2-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1 -yl]nicotinotrile 0 no-dibromo-7"-(;-pyridinyl ) 1( Piperazinil Jad Znb-111 [On ))1( ¢5, 7-dibromo-2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1 H-benzimidazole

Js sad methyl]-111-benz (1)-pyridinyl (7) piperazinyl Tse 00 ¢5-fluoro-2-[(4-pyridin-2-ylpiperazin-1-yl)methyl}-1H -benzimidazole dds 1-4-7 (7) piperazinyl](1(menhel)-111-benzimidazole ¢2-{[4-(1,3-thiazol-2-yl)piperazin-1-yl [methyl}-1 H-benzimidazole 1-7(-pyridinyl (Y) piperazinyl]-81-benzimidazole-1-carboxylate ¢isobutyl 2-[(4-pyridin) -2-ylpiperazin-1-ylmethyl]-1 H-benzimidazole-1-carboxylate yo “HY (dS)1(linedilurib(-1-[lethem))1(piperazinyl (Y)-pyridinyl) (1-7 2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1-(pyrrolidin-1 -ylcarbonyl)-1H-tbenzimidazole -1-lozademia methyl] -111-benz(1)piperazinil(1)methyl-77)-pyridinyl SUNN

N,N-dimethyl-2-] (4-pyridin-2-ylpiperazin-1-yl)methyl]-1 H-benzimidazole-1- carboxamide Y- ¢carboxamide ode dw [i ))1( Piperazinil Ji 4([-7 ¢2-[(4-phenylpiperazin-1-ylymethyl]-1H-benzimidazole 111-14-7-benzoimidazolyl(Y)methyl)piperazinyl(1)]-benzonitrile ¢2-[4-(1H-benzimidazol-2-yImethyl)piperazin-1-yl]benzonitrile Ye YAYA

41-7 -(7-chlorophenyl)piperazin])1(menyl)-111-benzimidazole ¢2-{[4-(2-chlorophenyl)piperazin-1-yl]methyl}-1H-benzimidazole EY -(7-fluorophenyl)piperazinyl [(V)mechethyl)-111-benzimidazole ¢2-{[4-(2-fluorophenyl)piperazin-1-ylJmethyl}-1H-benzimidazole 0 4- 7-(7-nitrophenyl)piperazinyl [(V)mel)-111-benzimidazole ¢2-{[4-(2-nitrophenyl)piperazin-1-ylJmethyl}-1H-benzimidazole (as Se ¥ ) £1) phenyl)piperazinyl])1(mgpyl)-111 benz saad ¢2-{[4-(2-methoxyphenyl)piperazin-1-ylJmethyl}-1H-benzimidazole]£ - (111-benziimidazolyl (V)methyl)piperazin(1)]phenol ¢4-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1-yl]phenol 01 7-((4- [7-methylthio)phenyl]piperazin (1)) aH (die imbdazole ¢2-({4-[2-methylthio)phenyl]piperazin-1-yl} methyl)-1H-benzimidazole a SHY ) EY phenyl)piperazinyl](1(mgyl)-111-benzimidazole ¢2-{[4-(2-ethoxyphenyl)piperazin-1-ylJmethyl}-1H-benzimidazole 0 4-7 - (111-benzimidazolyl(7)(fa-piperazinyl(1)]phool ¢2-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1-yl]phenol 1-([?; -(7-methoxy (Js piperidinyl])1(methyl)-111-benzimidazole ¢2-{[4-(2-methoxyphenyl)piperidin-1-yljmethyl}-1H-benzimidazole 7- (; 4)]-2;(HY)10-linideriborde ADT Fai (1-7methyl]-111-benzimisdazole ¢2-[(4-phenyl-3,6-dihydropyridin-1(2H)- yl)methyl}- 1H-benzimidazole or its salt; est cester amide or pharmacologically acceptable primitive var thereof. The two best compounds Gy of the present invention are: ve 41-5-(111-benz imidase and lyl (71)methyl)piperazin])1(pyridinol(V) $6-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1-yl]pyridin-3-ol and YAYA vA Menyl]-11-benzimidazole (1) piperazinyl (1) pyrimidinyl (2.7-7-[(4-pyrimidin-2-ylpiperazin-1-yl)methyl]-1H-benzim idazole According to the present invention is: Sams and the most compound

Js ad [(4-pyridin-2-ylpiperazin-1-yl)methyl]-1H-benzimidazole 1-7 .2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1H-benzimidazole Abbreviations The following abbreviations are used in describing subsequent diagrams and examples: boron trifluoride diethyl denotes a complex of boron trifluoride diethyl ether 8.017 '-di011 phospheno)- Jd '-di(thate) YY stands for BINAP tether complex stands for tributoxy 806 ¢2,2-bis(diphenylphosphino)-1,1'-binaphthyl Tefel 0.1 stands for dba ¢n-butyllithium asi stands for p-butyl nBuLi ttert-butoxycarbonyl J: 52 denotes dimethoxyethane DME 'dibenzylideneacetone on dibenzylideneacetone ¢N,N-dimethylformamide methylformamide SENN denotes DMF ¢dimethoxyethane 'ethanol J stl EtOH stands for tdimethylsulfoxide Jie stands for disulfide DMSO stands for TFA ¢triethyl amine amine Jd stands for tri-TEA for distilled methanol; Ju MeOH ve stands for tetrahydrofuran Ju THF 'trifluoroacetic acid On trifluoroacetic acid denotes TLC ¢tetrahydropyran denotes tetrahydropyran THP 'tetrahydrofuran p denotes a regular compound; ¢thin layer chromatography Thin-layer chromatography indicative of a tertiary compound; thn denotes a secondary compound; A. denotes a left-rotated component; A denotes a right-rotated component. © - 0 The following symbols are used: (NMR) and in the NMR spectra on a coupled spectrum; ; denotes a triple spectrum; The dud spectrum denotes a single spectrum; quadruple dus; « denotes a multiple spectrum; delta denotes difference; 1 denotes the coupling coefficient; Shaking indicates Horns. Mekha

In mass spectrometry (MS) the symbol miz is used to denote the mass/charge of the molecule; Jad is based on the mass/charge of the electron; 14 Jud over the molecular formula; 01 °C Jud on a chemical ionization source at atmospheric pressure; Jad EST is based on the ionization of electron spray. Preparation of the compounds of the present invention ° The compounds of this invention can be prepared by various synthesis methods. Typical procedures are described in the diagrams (0

YAYA vr 1 blueprint 1 chloroacetic acid 1 aa ,

R AL NH Shen Chloroacetic Re. Cl 8 oS 2 chloroacetic acid 5 m 8" / 0 HCI Ay

RY NH, © RYN

Ro Rp (0) (Y)

A

TZ

. . Ra { 2 se JOMF ATER 0 Rag LS (Y) + 7 | E: or | T Lala F \ > DMF S R W Nanaim O F 5200 V N

HN—~”Rf unambiguously © H 7 © 8 in the general form (¢)”; where benzimidazoles denote benzimidazoles 7 and -- can be prepared with their meanings mentioned in formula 10 as “A Rp Rp The “Rg” symbols are compounds of benzene-1,2-diamines, where benzene-0-”-diamine compounds are treated. 1 is described in Scheme 1 (its concentration is HCI and with an acid such as chloroacetic acid in the general formula) 1) with chloroacetic acid of the formula 2-chloromethylbenzimidazoles benz imidazoles Jie gy dS standard) for the production of compounds 2-chloromethylbenzimidazoles, and the general compounds of ?-chloromethylbenzimidazole (Y) of the general formula (¥) are treated with compounds of the formula General (0) in the presence of a base such as ternodeyl or potassium carbonate potassium carbonate ctriethylamine amine 01 or 111 dimethylformamide acetonitrile acetonitrile (Jie) in a solvent cesium carbonate (4). For the production of 5-benz imidazole compounds with the general formula NN-dimethylformamide Mkah vi 1 scheme A p ;

N ethanol Cs,CO; N

A-Y + \ oY heat) excess ds ( ) : J) Sat ~ or Br. Cl, =Y HN—"R, for or 8 Transitional (A)

A

N

A Ra 6 1 N (A) Remove protective assembly 5 1 Scheme Re: SN M A | =

HN Re R N c H (%) Rp (Me)

Jo where 0 ( 01 ) in the general form benzimidazoles Preparation of benzimidazole compounds (Sa on their meanings mentioned in formula 0) » as described in A Example Rp Re «Rp »Ry Symbols in the general form Scheme haloheterocycles. Where halogen heterocycles are treated ° piperazine atom block with an excess amount of piperazine chalogen representing halogen Y where 0 (0 ig and ic is a group of P in the general formula 71 where nitrogen ethanol in an ethanol-methyl solvent -C(O)OCH,Ph or -C(0)OC(CHy), for nitrogen as cesium with heating in the presence of a base as cesium carbonate n-butanol or p-butanol piperazines (or base) to produce piperazine carbonate Ve compounds from which the halogenated heterocycles Yau.(A) are treated with the general formula nitrogen nitrogen bond The piperazine atom of the general formula (1) and piperazine compounds

Wagaw and Buchwald, JOC with a transition metal catalyst as described in reference (V) in the general formula

Yang or Ref. Harris etal, JOC 64 (1999) 6019-6022 61; in Ref. (1996) 7240-7241 for production of piperazines and Buchwald, J. of Organometallic Chem. 576 (1999) 125-146 Ve and group 0 can be removed. (A) with general formula nitrogen 313 sa piperazines with general formula nitrogen piperazines CUS ya protective for

YAYAve

(A) Using conditions known to those skilled in the art. For example, acidic ish can be used to remove (ia -C(O)OC(CH;), trifluoroacetic acid in methylene chloride or HCI (concentration; N) in lS gt) -1,4 dioxane Hydrogenation conditions can be used, such as using palladium 8 loaded on carbon under a pressure of hydrogen ranging from 1 atmosphere pressure to ; atmospheric pressure in a solvent such as methanol, ethanol, or ethyl acetate to remove -C(O)OCH:Ph. Scheme 1 to produce vehicles

benzimidazoles in general formula (01).

N= Re alkyl Re 806 (7 ) Rmq Li =M Boc (\Y) 7 m ~ R A "m 1 | m ; ( 1 Scheme Bn — N R so. benzimidazoles Preparation of benzimidazole compounds (Sa) according to their meanings mentioned in formula (1) as described in (Rp (Re «Rp «Ry], the symbols tert-butyl 4- in the diagram?. Where ¢ - is treated oxopiperidine-1-carboxylate th-butyl 2 with a heterocyclic ring (Aldrich buys from Aldrich coxopiperidine-1-carboxylate ws ES or organolithium reagent with general formula (0) and organic lithium reagent alcohols and alcohols are treated i 1 9 in the general formula alcohols for the production of Grignard alcohols for the production of tetrahydropyridine thionyl chloride compounds with thionyl chloride (V7) in the general formula and treating tetrahydropyridine compounds with the general formula (10) in the general formula tetrahydropyridines Ve to produce compounds 1 as described in diagram (A) with general formula tetrahydropyridines 0 1 5 (with general formula benzimidazoles benz imidazoles

YAYA

In the diagram 4 A 0 OH 2 A-Y ~~

AN > 5 + | or Br. 0 | = YRM Ce

MNT Re alkyl Alkyl - 8 NT Re

Cbz (*) MgBr j Li = M Cbz (“Y) (4) A

A A Ra a Ed H M : Rg- |. Be my brother

Y. ( v4 ) ( ) Rp (1) where (YY) in the general form benzimidazoles denotes the preparation of benzimidazoles (Sa) as described in (I) to their meanings mentioned in formula A and Rp Rp «Re «Rp «Ry Symbols benzyl 4-oxopiperidine- -benzyl carboxylate 1- The scheme Where ¢ - oxopiperidine ° is treated with an Aldrich heterocyclic ring Normally: <50: 1- It buys from the Aldrich company or Grignard organolithium reagent with the general formula (0) and lithium organic reagent alcohols and alcohols are processed. (1 A) with the general formula alcohols to produce Grignard alcohols for the production of tetrahydric compounds And pyridine thionyl chloride Jui ot with chloride (1 A) in the general formula tetrahydropyridine lS ye in the general formula (3). The tetrahydropyridines 01 palladium (Jia) are treated with a transition metal catalyst (0). With the general formula tetrahydropyridines for the production of piperidine hydrogen compounds in an atmosphere of hydrogen carried on carbon with the formula piperidines and piperidine compounds can be processed (Y 0) with the general formula piperidines benzimidazoles for the production of benzimidazole compounds 1 As described in the general diagram ( Y. ) 0 ( Y \ ) in the general form Ve

YAY A

VA

© Scheme tBUONO aq OFt (A K,CO- no DME / 002 TO MeOH ae “N° ~cl 85 1) anhydride (x 0 ng Nid b acetic anhydride

Oh

O_o

TT i © 0 ~ N 0 1 The hottest scheme The scheme? or RaCN

POL ~~ Rew -N N—Rp 03 Tr “NT el Re” TN hydroxy.sSsoud or protective group “1 Ro 7) (YY) (Sa) Preparation of benzimidazoles with general formula 9 0 where symbols denote “Ra mk Rp Re and Re have their respective meanings in formula oI) as described in ° chart #©. Cua treats 8-amino-7-chloropyridine ¢S-amino-2-chloropyridine purchased from ¢Aldrich as described in ref. 9 Lynch et at., Tetrahedron Asymmetry and Koch and Schnatterer, Synthesis (1990) 499-501 2791-2794 (1998)” for the production of 17-chloropyridinecyl acetate. (7) 6-chloropyridin-3-yl acetate and -chloropyridin-dinol (9) -6-chloropyridin-3-ol. Treats “-chloropyridinol (79) 6-chloropyridin-3-ol or Ve acetate 7-chloropyridin (¥) 6-chloropyridin-3-ol as described in Schematics 1 and ? to produce benzimidazoles with the general formula (YY) and alternatively “al-chloropyridinol (7) 6-chloropyridin-3-ol with a hydroxy buffer reagent J fa hydroxy benzyl bromide or benzyl chloride in DMF with a base such as cesium carbonate to produce buffered chloropyridines 10 hydroxy is of the general formula (TY), where PT represents benzyl, and the hydroxychloropyridines are treated with the general formula (Y ¥) as described in the two diagrams or Y to produce yu imidazole compounds benzimidazoles with general formula Y 9 (after removal of the hydroxy protective group using standard methods to remove the protective group known to those experienced in All for example Jad YAYA va can be removed using a catalyst From a transition metal such as benzyl hydrony the protective group of hydroxybenzyl in hydrogen carried on carbon 0 in an atmosphere of hydrogen palladium palladium cleavage acetate or alkyl acetate ethanol methanol methanol (ie solvent 1 example 2-[(4-pyridin-2-methyl]-111-benzimidazole)(1)-[7-maleate]; -Pyridinil (7) piperazinil 2016AD helped M-111-[1 bgt p (bg 1-snug and c except maleate 11 ge 2-{(d-pyridin-2-ylpiperazin- methyl]-111-benz imidazole) (1) ; 1 mmol) to a rapidly stirred solution of 5.9 g 2-chloromethylbenzimidazole in a large DMF vial ml of VO in 1-(2-pyridybpiperazine of 1-(7-pyridyl) Piperazine 0.0 ml V.M. within 2 minutes. Add 0 at Ale in a round bottom flask bath for 11 hours. The reaction mix for oa (equivalent) triethylamine amine J of thirty on full consumption of the raw material. Then the reaction mixture was treated with *ml of TLC until dl ve ml of water slowly drop by drop. And after Ve followed by adding triethylamine triethylamine ml tov and washed with 9001100 filtration by sucking x a Toa for one hour; of water and dried to yield 9 g of the product. The solid was recrystallized twice in p-butanol, gm of the compound called the title, in the form of a yellow powder, VT, boiling with n-butanol.

HONMR a YYV=YY oe Melting Point (AVY Orange (Pure Product Percentage x Hm) €,0 =) 4H) 27 (5a m =) 4H) Y,00 Ub MHz) 001 (CDy,SO)

QH) HRA AY AY LAH aH) LAY Card 6.0 Hz) LY =T dH (2H) LY

Y4¢ m/z (NH/DCI) MS .) ps VA rub (IH) A,+4 h 3H) V,0A=Y,£) (m (M+H)"

YAY ON passed iH .16.25 CCH Ns theoretical analysis of the formula Ye

YAY ON 0A tH 19, EY p: ee Analysis by YAYA

A

2-[(4-pyridin-2-methyl]-111-benzimidazole)(1) maleate 7-[(;-pyridinyl (?) piperazinyl]-ylpiperazin-1-yl)methyl]- 1H-benzimidazole maleate in maleic acid mg TOV and ivy maleic acid Mix 1.16 g of example product to cause dissolution with moderate heating. room temperature and the resulting solid was collected by filtration and crystallized in the form of a white powder.The melting point of maleate salt produced ethanol 1-8 M.

AV, iC CH Ns. CH 04 Theoretical analysis of the formula

AVY IN letter TH 7 curl; iC Practical analysis: 0? Jeu 2-[(4-pyrimidin2-imidazole znb-111-]lithium (1)"-1); - Pyrimidinyl (?) piperazinyl ylpiperazin-l-yl)methyl}-1H-benzimidazole using BY Prepare the compound named with the title following the morphological procedure (LeDrip-7)-1 instead of 1-(2-pyrimidylpiperazine) piperazine (Ledimirib-7)-1 ve melting point DMF and use 011,011 as a solvent instead of 1-(2-pyridyl)piperazine FLAT (4H) (H < 0.3 mgms) Delta 01 11 NMR AY Van Arla (2H em) V,YY (IH Hevel © =J “t) 1,0 (2H D (4H em) 1 21 ot ) (M+H)" 1 m/z (NHy/DCI) MS (2H of © =T spin AY ¢(2H cbrm)

YT, GN CLAN GH 17,06 CCH 13Ng(0.25 CH yy) Theoretical analysis of formula 7

LE) ON £14) SH 15,61 GC Experimental analysis: Example? Ji) (1p methylpyridin-2-yl)piperazin-I-yl]methyl}-1H-benzimidazole lithium-(-1 using oY Prepare the named compound by following the example procedure Yeo "-pyrimidyl)-1 Instead of 1-(6-methylpyridin-2yDpiperazine) piperazine ((Y) pyridinyl as a substitute

M piperazine 'H NMR .1-(2-pyrimidyl)piperazine (00:00; 01 mV) delta Y,00 =J «t) VAT (3H os) © from VAY (4H and ] = © from TTR (Z (2H ud) TAL h la do wd) VOY (IH c 4 hen (2H em) V,YS (2H em) V,09 (IH) «dd) 7 ]= Aa 5 Hn (MAH) Yo A m/z (NH/DCI) MS «(1H : Par 4 "-[-(111-benzimidazolyl (7)methyl)piperazinil] (1) Nicotinonitrile 2-[4-(1H- benzimidazol-2-ylmethyl)piperazin-1-yl]nicotinonitrile Prepare the compound named with the title following the oF example procedure using 1-(?-cyanopyridinyl ) 0 piperazine 1-(3-cyanopyridin-2yl)piperazine instead of 1-(7-pyrimidyl) 0 piperazine a 0 1Q-pyrimidyDpiperazine & fusion 10H 0M. (CD,0D) "HNMR 0 MHz delta a) YVY h 1 mil (4H no nick h 1) is YAY (4H (y) (2H LAY) z z h TY they o (m 2H) V,YY (1H aa “(IH cbrm) hr”dd) Zahla ¥ mL dd) AYO “(1H ¥) from (MHH) 14 m/z (NHY/DCI (MS (TH) theoretical analysis of the formula CppH Ny p: ON 60,1 tH TY, TA date ve practical analysis: YE IN oY tH IV, A) iC Example 5 0) non-dibromo -7-[(;-pyridinyl(Y)piperazinyl HY [de))1(imidazole 5,7-dibromo-2-[(4-pyridin-2-ylpiperazin-I-yl)methyl]- 1 H-benzimidazole Prepare the compound named with the title following JL procedures 1 and 1b using the sap SET of Y. = ?-phenylene (SE) 4,6-dibromo-1,2-phenylenediamine instead of L From (Y= gel SE ?-phenylene diamine 4-fluoro-1,2-phenylenediamine in the article (alse 001 CDCL) 'H NMR J delta 01 0n 3-1 Henl' (4H mm of) 1 h 1 mL (4H 50 (z) “(2H am) NY (2H frla (x) (2H arla) (1H brm) (fos m/z ) NH,/DCI) MS (1H “m) AYA Teml AM+H)™ fet veo Theoretical analysis of the formula: C 1Cyl pB Ns tar oN YA tH ram Practical analysis: No, YN IN YAY cH 44,137 iC Metkha

AY

S-fluoro2-[(4-imidazole znb-111-]lithium) (1) piperazinyl (1)©<fluoro-7-[(;-pyridin-2-ylpiperazin-l-yl) )methyl]-1H-benzimidazole Example A+ 5-fluoro-2-chloromethylbenzimidazole 5-fluoro-7-chloromethylbenzimidazole ° med mmol) of 4-fluoro-0'7-phenylene diphenylene YAY ) Add 0 g c4-fluoro-1,2-phenylencdiamine to an order of 0 g (Use 0 ml) of chloroacetic acid and YO ml of HCl (concentration 1 M) to the 0 mL round bottom flask Heat Jeli ge at 45 C for 11 h Cool the mixture to 0 °C room temperature and adjust to 16:00 Extract 0 mL ethyl acetate times Each time al dag over MgSO, filter and concentrate under reduced pressure.Purify the product on SiO2 by using a mixture of CHYCL/MeOH in a ratio of 701 mm yielding a brown foam (production rate - ¥71/( 0301 «CD;0D) 'H NMR mH) «(2H brs) €,AV Lh m (Ye =) id), 5 (TH odd) Lyd 5.5600 hml 18) 00 (MH) YAS m/z (NHy/DCI) MS (1H an) V,00=V, Example B ©-fluoro-?-[(?-pyridinyl (Y) ) piperazinil (1(methyl)]-11-benzimidazole 5-fluoro-2-[(4- pyridin-2-ylpiperazin-1-yl)methyl]-1H-benzimidazole Ts compound Labeled with the article's procedure breadth AY - using ©-fluoro-”-chlorobenzimidazole instead of “-chlorobenzimidazole 701 (CD;OD) 'H NMR .2-chlorobenzimidazole meg ahs) delta (2H hen t k (y 1 -1 ot) 1 y-mm (4H Hn©,A =T at) 15-75 “dd) VY under 6 “d ) TAY (IH a ]= 4 edt) VY (1H melody AY = A 0) 2H ah s EA (TH Oa dd) V, YE (TH 0 y) M+H)" YAY m/z (NHy/DCI) MS (1H d (x) Theoretical analysis of the formula iC 1Cy7H NsF#0.20 MeOH bright SH

AY

Y,VY GN 11,15 95: I hate iC Practical analysis:

Y Ji 2-{[4-(1 3-thiazol- -111-benzimidazole lithem) [(V)piperazinyl (TF) 7-thiazolyl 1g 2-yl)piperazin-1 -ylJmethyl}-1H-benzimidazole For example: 1-(2-thiazoyl)piperazine) piperazine (-7-(-1”-2-bromothiazole g l 10 mmol) of 71-bromothiazole V,Ve Added mM TY (g) +, Y «cesium carbonate g (4 mmol) of 058 mmol cesium carbonate) from Schflashi (dual LY) 17 g and racemic BINAP Racemic BINAP mol) to tris(dibenzylideneacetone-dipalladium (0) (Lia) palladium SD benzylideneacetone) Ve

Jf ESS Nizarpipe-1 mmol) of Ve VE) 1 g absolute of Heat the mixture to toluene in t-butyl 1-piperazinecarboxylate ethyl acetate 1 hour and chill. The reaction mixture between water and acetal acetate was distributed 11 times by reflux for a period of more than 14880, and the Cia corganic layers were concentrated under pressure, and the organic layers were mixed at a low level. Purification by column chromatography containing 80 flash ts resulted

N-Boc piperazine derivative 8067 g of piperazine derivative 46 flash SiO, column 2,549 g (VT = p LY) desired yellow solid (concentrated for HCI) ml of A with Boc-piperazine (mmol) of the 306 piperazine derivative 14) was brought back to celal pH for 0 minutes at room temperature. The reaction mixture was diluted 0 ethyl acetate solid and alkyl acetate extract NayCOy pH ranged from / to 9 b And the organic layers were mixed; washed with brine water and dried over 0.14:50, and the filtrate was concentrated under 1.77 grams of the compound called the title in the form of a solid 1.77 at low pressure, resulting in yellow. It was used without additional purification. Example / AB 2-{[4-(1 3-thiazol- -111-benzimidazole {Je])1(7-)1;-(A; 7-thiazolyl (7)) piperazinyl ye 2-yl )piperazin-1-ylimethyl}-1H-benzimidazole H

At Prepare the named compound with the title following the procedure of Example 1a using piperazine 6:2106C1M(1A2-1820)-1 instead of 1-(7-pyridyl)piperazicin (lylozathe-7)-1oo “(CD3),S0 ) 'H NMR . The melting point? M 1-(2-pyridyl)piperazine «(4H (a =] ct) VENT EY (4H HFZ 0A =] delta 17-7848 0n (Ale of 1 -[ dd)VA 2H am) VY oY) (TH mL Y=) «d] kDra (2H (e 4° (MFH)” 1 m/z (NHyDCI) MS (1H em) V,eV=V,0¥ ( 1H em) (1H

YY, VIN $0,VY SH iC iCysHaNsS#0.25 11:0 Theoretical analysis of the formula IN 0.8 tH 04.7 iC Practical analysis:

A Example isobutyl taliscoperc-1-lozademia znb-111-[lithem (1) piperazinyl (YF) 1-7)?<pyridinyl|0 isobutyl 2-[(4-pyridin-) 2-ylpiperazin-l-yl)methyl]-1H-benzimidazole-I-carboxylate dichloromethane was added ?, .; 3 mmol) of isobutyl chloroformate 1 ml of 1 fa1 to a stirred solution of Lala,; g ( 1, mmol) of compound Example 11 and stirred the mixture at room temperature for dichloromethane dichloromethane concentrate by chromatography on a Tig column under reduced pressure 3 TSH h; 0601800/Dichloromethane SIO; flash containing 1g of the compound named with the title in 1.5 fng YY in a ratio of dichloromethane (Mifamers Lab) 01 "CDCL) 'H NMR (£3 ) Oil image (production rate - hot “(4H bm) for winding bm) YA ton am) Y, YY (6H here T=) “d) 0 (1H em) VRLA” (2H em) V,¥e «(2H em) NN (2H eml V =) od) £5 «(211 bs) 0+ (M+H)" 4 m/z (NHy/DCI) MS ( LH em) AVS «(1H em) 57 be em) VY, V3 3 Example carbonyl)-111- (1) (pyrrolidinyl - [de)1( "-1(? - Pyridinyl (7) piperazinyl 2-[(4-pyridin-2-ylpiperazin-l-y)methy!]-1-(pyrrolidin-l-ylcarbonyl)- 1H- J 5 Jawad yu benzimidazole Yo

YAYA

As mmol) of 1-pyrrolidinecarbonyl chloride (eT) were added 4 mL and 179 mL (©£ mmol) of two ethylamine 1-pyrrolidinecarbonyl chloride mmol) of compound Example 1a in VOY ( to a stirred solution of 0.17 g triethylamine and the mixture was heated in a sealed flask dichloromethane ml of dichloromethane 1 kg per hour; it was left to cool to room temperature and diluted with chloromethane 1" for a period of time, its concentration was 6 gfths and 600xft under NaHCO pressure, washing with low dichloromethane, and purifying the ore by chromatography on a flash column containing .50 lye yielding 4 g 0 with a ratio of ethyl acetate < ul fhexanes using a mixture of 171-hexanes 171 Melting point: (Ee = z LY) of the compound named with the title (modified)

YAY (4H am) 01 netea em) 1 =), VE Lah (Galea 01 CDC) 110318 0 (BI em) VY «(2H em) 1.10 (1H am) £, YY (8H bm) 5 ( 1H plus (MEH) 241 m/z (NHyDCI) MS (1H am) AYA (IH am) Hela (1H an) 4

XY vf aN (lvt tH VV) e: iCpHNGOL 1/2H,0 Theoretical analysis of the formula

XY) ON MAMET SH ALYY ©: EXAMPLE ANALYSIS: 01 Example Vo-1-lozademia methyl]-111-benz (1) dimethyl-1,7)-pyridinyl (7) piperazinil ,

N.N-dimethyl-2-[(4-pyridin-2-ylpiperazin-1-yDmethyl]- 1H-benzimidazole-1-_ carboxamide using OLA 4 chloride Prepare the named compound by following the -pyrrolidine procedure 1 Immunofluorescence 11,1-010611:716 instead of methyl carbamoyl chloride (JUN Nv 'H NMR . M YWA-IVE 00A1-001101066. Melting point: Jue S chloride p (3H bm ) 71 (3H bm) 7, ? (aH bm) Y,TA MHz) delta 001 (CDCL) mkila (BH h (x (2H am) VTE (1H bm) £,Y « (IH bm) (4H cbm) (M+H)" ft m/z (NHyDCI) MS (1H (x ANA (1H to V,Y3) "(1H "m)

XY, OTN CLE SH 10,3) iC iCypHuNO Theoretical analysis of the formula Yo

YY,AY GN 1,0 tH 19, YA iC Practical analysis: ‎

5m Example 11 “7-phenylpiperazin ((1)methyl]-111-benzimidazole 2-[(4-phenylpiperazin-1-yDmethylyl- 1H-benzimidazole) Prepare the compound named by following Example procedure?using 1-phenyl° I-phenylpiperazine instead of 1-"-pyrimidyl)piperazine .1-(2-pyrimidyl)piperazine Melting point: 186-760 °C. (alka 001 (CDOD) 'H NMR delta 00 (4H am) «(4H «m) v, va md (z «(2H cm) AR «(2H «m) Y, eA «(1H cm) 1,4Yv «(2H nah no «(2H em) x (M+H)" 47 m/z (NHyDCI) MS (2H em) Theoretical analysis of the plastam formula: SH EYE AE SC tarrk 1 empirical analysis: cH YY, VRC 61.44 l rub example VY "-[; = ur HY imidazolyl (Y)methyl)piperazinyl](1) benzonitrile 2 -[4-(1H-benzimidazol-2- ylmethyl)piperazin-1-yllbenzonitrile Prepare the compound named with the title following the example procedure ? using 1 Vo-)7-cyano(Jud)piperazine 1-(2 -cyanophenyl)piperazine instead of 1-"-pyrimidyl)piperazine 1-(2-pyrimidyDpiperazine) R score: HNMR .p YYY=YTN (Gaba 0 «CD,0D) delta (4H am) A ((2H 1s) YAS (4H am) “(IH am) VV Rla (1H em) 0.17 (h” (2H Tefla m/z (NHy/ DCI) MS (4H em) M (M+H)T vy. Theoretical analysis of the formula SH VY, 90 iC CH oN; NRT YY, eV IN Practical analysis: AN LT IH YY, VC 7.13 Ex 11 1-7[-(-chlorophenyl)piperazinyl Js aad ir HY = {Je ])1( -2-114-2 chlorophenyl)piperazin-l-ylJmethyl}-1 H- benzimidazole Yo Prepare the compound named with the title following the example procedure ? using 1 7-chlorophenyl)piperazine 1-(2-chlorophenyl)piperazine instead of 1 -(7-pyrimidyl)a

L-Piperazine Aa 3. 1-(2-pyrimidyl)piperazine Anisar: P'H NMR . oY (4H em) 501 (4H am) 07 LA (Gale 0 “CD;0D) qa (2H es). Gea Yd =) dd) VEY (IH em) (MH) 371 m/z (NHyDCI) MS (2H em) V,Y® “(2H “m) 28” (1H oe) For the formula 1C CH CIN mart SH abbreviation AVY EN Practical analysis: iC not all crunchy AVY, V0 iN Example 4 1 "-11-(7-fluorophenyl)piperazinyl mH) = {die ])1(imidazole-4-2])-2 fluorophenyl)piperazin-l-yllmethyl}-1 H-benzimidazole 0 Prepare the compound named with the title following the example procedure using 1-(7-fluorophenyl) Piperazine 1-(2-fluorophenylpiperazine instead of 1-(7-pyrimidyl) piperazine 1-(2-pyrimidylpiperazine) Melting point: TE-YTY M - 'H NMR (Gale 0 "CD; 0D) delta 1.57 (4H an) YE (4H am) 17 (E tend both (MH) 1 m/z (NHyDCI) MS (2H em) V,1 «(2H an) V,02 (4H “m) ve theoretical analysis of the formula iC CH PN, Tekt IH enlightened IN brain practical analysis: : 14.00 tH thartel AANY yo Jud = F ] 2-(7-Titrophenyl)piperazinyl {de ])1(-111-benz Js aad -4-2])-2 nitrophenyl)piperazin-1-ylJmethyl \-1H-benzimidazole Ts 2 Compound named with title following example procedure Y using 1p7-nitrophenyl)piperazine instead of “TY pyrimidinyl)piperazine 1(2opyrimidyDpiperazine) and purification was performed using a mixture of acetonitrile TFA acetonitrile as the elution mixture on Jala reverse phase support to produce the title compound as the TFA salt HNMR xe (00:00; 001 megams) Y,AS Bl ls ltna em) 5701 fin 77 b (2H es) YAYA

AA m/z (NHyDCI) MS (3H «m) Y,VV «(3H em) ¥,0V «(1H «m) V,T¢ (1H «m) VY (MH) 8 11 Example 2 -)14-2- Js aad yur HY {dda ])1( methoxyphenyl)piperazinyl ¥) = £137 methoxyphenyl)piperazin-1-yl methyl}-1H-benzimidazole 2 using Ve prepared the compound named in the title Following the example procedure (7-nitrophyl)-1 from Yu 1-(2-methoxyphenyl)piperazine (Jd <methoxy Y )-1

Lab (alse 0 «CD;OD) 'H NMR .1-(2-nitrophenyljpiperazine) Piperazine VAY (IH am) Vo es) YF (3H (TAT (4H em) ¥, £7 (4H em) YOY

YY mz (NHy/DCI) MS (2H dogs (x) (2H a) ola (2H «m) 5 (1H am) ve

AM+HY 117 Example 4-[4-(1H-benzimidazol-2-phenol])1(methyl)piperazinyl (Y)imidazolyl Znb-11)—¢]-¢ yimethyD) piperazin-1-yl]phenol The compound named with the title following the example procedure? using pT aa Ve instead of 1-(4-hydroxyphenyl)piperazine piperazine (J -hydroxy ¢ )- 1 gaa NV Aa ya. 1-(2-pyrimidyl)piperazine 7-pyrimidyl) piperazine - 1 (4H em) stink 6 am) 1 501 (Gale 001 “CD;0D) HNMR TM.

MS (2H < m) VA «(2H «m) Vv, «(2H «m) Vv, YY «(2H «m) 1,4Y (2H s) ed (M+H)" 1 m/ z(NHy/DCI)Y.

YA Example ‎Jad 3H —(die (0) dis ‎7-(41-[7-(Mgyl-5(Fyl)) 2-({4-[2-(methylthio)phenyl]piperazin-l-yl} methyl)-1H-benzimidazole dian ub Prepare the compound named with the title following the example procedure ? “CDCl;) ‘H NMR 0 C 101-1710 Fusion: As jd. 1-(2-pyrimidyl)piperazine piperazine

hm 00 megams) delta 7.4 (3H es) yeah? (4H em) A (4H cm) s «(2H es) (3H am) 17 (IH em) V7 rla V,24 «(2H an) (x 21). MS (l/mL) m/z L(MHH)T 3 A theoretical analysis of the formula iCioHpN,O. 1/4H0 p: 11,08 ON 1,1) GH Art 2 Practical analysis: VLYY RC Tel Nef Tartel Example 15 (SEY) 1-7 phenyl)piperazinyl])1 (methyl-4-111-benzimidazole -2-114-2 cthoxyphenyl)piperazin-l-yl methyl}-1H-benzimidazole Prepare the compound named with the title following the procedure for the example ? Using (1 01-) 7-ethoxyphyl) piperazine 1-(2-ethoxyphenyl)piperazine instead of 1-"pyrimidyl)piperazine 1-(2-pyrimidyl)piperazine Melting point: H?-. 0.5 “CDCl;) 'H 1118 0 Yo mHZ) t) 1.40 Lh [= Hana Y,v4 “(3H 417 th Lh) (4H 5” (2H 5) Akh (3H am) VY (BH am) Vo TTA (2H Geet TT) “q) Other m/z (NHy/DCI) MS (2H “m) N (M+H) (” ae Theoretical analysis of the formula ATN0 IN EY, TH YY Ee tC Ca HaNO Practical analysis: p: karacht ATL) GN ETA SH Example Yoo 111 (-41-7 benzimidazolyl (”) methyl)piperazinyl [1]phenol 2-[4-(1H-benzimidazol-2- ylmethyl)piperazin-1-yl phenol .¥ Prepare the compound named with the title following the procedure of the example ? using 1 -) 7-Hydroxyphenyl)piperazine 1-(2-hydroxyphenyl)piperazine instead of 1-"-pyrimidyl)piperazine An 53. 1-(2-pyrimidyDpiperazine Analogue: A + 1177m'H NMR (0 mHZ) am) Y,VA Lbs TAY “(4H am) (Y Lad 1,40=T,AT” (2H < m) m except The (1H ¢ but “dd) response to the Y modulus MS (2H cm) V,04 (1H (MHH)” 1 8 m/z (NHY/DCI) 0 dye theoretic analysis iN CTY TH TAN Y IC iC isHpNOL12H,0 edited by YAYA

Practical analysis: tH AYE CC DIRTE IN Garla Example YY 71[-(7-methoxyphenyl)piperidin J and rH = {J ](1) -2-114-2 methoxyphenyl)piperidin -l-yl]methyl}-1 H-benzimidazole Q. a mixture of 1.7 g (10 mmol) of 4-(7-methoxyphenyl)piperidine ¢4-(2-methoxyphenyl)piperidine 7 g ) of 0.1 mmol) of 7-chloromethyl-benzimidazole, 2-chloromethyl-benzimidazole and 0.17 g (11 mmol) of 08:00 in A ml of DMF at . room for YA hours. The reaction mixture was poured into 0 ml of water, extracted with 51 ml of ethyl acetate, the organic layer was washed twice with 0 yo ml of brine each time, dried over 0850, filtered, and the filtrate was concentrated under reduced pressure. 0 And the ore was purified by flash chromatography, Joga ally, with a mixture of methanol in dichloromethane at a ratio of 8, resulting in AY mg of the compound called the title (production rate - NMR 7Ye) for (MAA 301). megams) delta (1H am) YAY (2H em) 4 (4H em) 0.4 q (x “(2H ae) TAY (3H is) TLYY (2H ys” Example YY converts dium pat (7) piperidinyl (1)methyl]-111-benzimidazole 2-[(4-pyridin-2-ylpiperidin-1-yDmethyl]-1H-benzimidazole 0 Ex 77 ;-hydroxy-; “pyridinyl(?) mmol) of 7-bromopyridine (2-bromopyridine) in 01 ml from 1118 to -0°C and was treated dropwise with 8.7 ml (0.Y) mmol (Ye) of nBuli ( Its molecular concentration is 1 μt in hexanes, and the reaction mixture was stirred for 1 minute at minus 00 C, then 1.14 g (9, ;) was added. mmol) from; -EXO-1-BIPERIDINE YAYA

benzyl 4-oxo-l-piperidine carboxylate in 10 mL of THF was slowly added to the reaction mix. The reaction mixture was stirred at -60°C for 11 minutes and then irrigated with saturated NHC. The cooling bath was removed and the Bay reaction mixture was left to room temperature. The mixture was extracted with CHCl, the organic layers were dried over MgSO, filtered, and the filtrate was concentrated under reduced pressure. The ore was purified by flash chromatography using a mixture of hexane ethyl acetate at a ratio of V 1, resulting in 400 pila. of the compound named with the title (rate 0 «(CD;,SO) 11 NMR . (177 = z ty megams) delta (4H am) 0.84 «(4H em) 71 «(4H «m) 058 5 (h “(4H) b (y V,Yo (IH ts) ©,Y0 “(2H bs” (SH “m) Y,¥o” (2H var (IH em) VV (IH an) yy MS (1H am) (MFHT YAY m/z (NHYDCE) 0 Ex. 7b; -(pyridyl (7)) piperidine 4-(pyrid-2yl)piperidine Heat 14 g (0.74 mmol) of example product 7a in + mL of thionyl chloride was refluxed for 2 hours, cooled to room temperature, Vo, and concentrated under low pressure. The ore was treated with ice and NaOH. Its concentration is 740, then extracted by O©,:0©11. The organic layers were separated, washed with brine water, dried over ,50,:H8; Cin Thy “Ss” filtrate TTY mid mg of the product dehydrated. product tell, then hydrogenation of the raw dewatered product using pile YOu of palladium Pd carried on carbon at a ratio of 1/7 at a pressure of Te pound per square inch (psi). Ye, and a temperature of 450 hours in Yamam, resulting in 500 mg of the compound called the title (production rate - 744). (NHy/DCI) MS AL (MAH) VY EXAMPLE 1 71g t(?-pyridinyl(Y)piperidinyl_(1))methyl]-111-benzimidazole 2-[( 4-pyridin-2-ylpiperidin- l-yhmethyl]-1H-benzimidazole veo 8 1 g 0 YY (mmol) of the example product? TY ef 0 g FI (mmol) of 7-chloromethyl-benzimidazole 2-chloromethyl-benzimidazole and AY PNR

AY

h. YA at room temperature for DMF ml of A mmol) from ,5900 at

J mL of acetate in 10 mL of water and extracted with 0” and decanting the reaction mixture 1 mL each time; dried 51 and washed the organic layer twice with brine with ethyl acetate, centrifuged and concentrated the filtrate under reduced pressure. And they etched the MgSO ore over its concentration of CH, CL/MeOH by flash chromatography with a mixture of (01 megahertz (CDCL) 'H NMR 111.) of the compound called the title (production rate - (2H). Nb (Z (2H am) 6 L (1H am) Y,V4 «(2H «m) 0 «(SH am) 0.1 Lb m/z (NHy/DCT) MS «(1H am) A £3 «(3H am) V,00 (1H am) 74 (3H am) VY, 4 (MAH) YAY

YY Example VL 2 [phenyl methyl]-111-benz imide azole (HY) 1-linidiboride <-di(P= 7-[(;3,6-dihydropyridin-1-(2H)-) yDmethyl}-1 H-benzimidazole except aYY Prepare the compound with the title as described in the example Use 4-phenyl-0-hydrochloride;7 9 1-tetrahydropyridine instead of — (pyridinyl) ¥(( piperidine d) -phenyl-1,2,3,6-tetrahydropyridine hydrochloride 1 drop of CDCly + 1 drop of CD;OD) 'H NMR . Lala (Y “(2H am) Tech (2H”) YoY “(2H cm) Y,4 megams) Delta 0001 (TFA

MS (2H am) No (2H am) P «(2H am) VY, £3 «(3H to V,¥¢ (1H am) R (M+H)" 0 m /z (NHy/DCI)

Ye Jt Y. 2[(2-methyl-4-methyl]-111-benzoimidazole) (1) piperazinil (7) dbs perm 8 = diem TF pyridin-2-ylpiperazin-l-yl ymethyl]- 1H-benzimidazole

Ive eg 3-methyl-1-pyridin-2-ylpiperazine ( piperazine ) Y) linidirip-1-lithium-1 hydrobromide Ye qr

Mix 1 g (0 mol) of a racemic mixture of 7-methylpiperazine and 01 ml (0.11 mol) of Y “2-bromopyridine” and heat at 011” for an hour VT. The reaction mix cooled to ? m and distributed between ethyl acetate (JY) and water. The layers were separated and the aqueous layer was concentrated under reduced pressure. 0 The ore was pulverized with ethyl acetate, dichloromethane, and methanol, and 450 mg of the compound called the title was produced in the form of a white-yellowish solid (production rate - 177). A 11 Yoo) MBghhman ((CD5). 2H “m) Vo “(1H 21 Aaah” dd) sah rkaf LA hen ed (LAA) 1H 00 lah AY henl (IH tara (IH cbs) ANY “(IH em) ) A, Ve (TH em).

(M+H)" YVA m/e (APCI) MS ¢(1H bs) A, AY

Example 4b-[(7-methyl-;?-pyridinyl(?)piperazinyl))1(methyl]-11benzimidazole 2-{(2-methyl-4-pyridin-2) -ylpiperazine-1-ymethyl}-1H-benzimidazole

1.8 g VAY mM (Use) of example product Ye in 01 mL of SENN methylformamide NN-dimethylformamide at 0 C was treated slowly with a solution of TY g VAY) mmol) of 7-chloromethyl-111-benzimidazole 2-chloromethyl-1H-benzimidazole in 10 ml of SENN methylformamide NN-dimethylformamide and after a few minutes the mixture was treated with + g 0 AY (mmol) of cesium carbonate and the 0 cooling bath 0 was removed and after 1 hour; The reaction mixture was diluted with ethyl acetate, washed three times with water, then with brine, dried over 4:50, and the filtrate was concentrated under reduced pressure. The ore was impregnated on a silica gel and proceeded (by lysing with a mixture of methanol /\—(dichloromethane at a ratio of 17) and yielded Yo) mg of the compound named with the title (production rate - (TY) melting point YAY LY (Yor) 11 NMR vo mefahms; 50.0, i)) delta VA (k) = + from YYA (BH) about 0.27 em (1H am) 11 (2H am) 1 (k]= 4 hun mkha at lah raf 1.1 from edd) LY (IH do VEE] od) khud (2H am) female (1H (IH em) AA (3H am) Baak (2H am) 4 (IH MSn AE H ed) LAY (1H (MH) Yo A mie (ESI) MS ¢ (1H ¢bs) 07

YY, VA CN Takht tH A iC Theoretical analysis of the formula: GH VN 0 iC Practical analysis: °

Yo methyl-4-pyridin-2-ylpiperazin-1-yllmethyl}-1H-benzimidazole iyo eg ss dT) (8) me (Js ree) ot mol) from ?- 0 5 Aldrich (S)-(H)-2-methylpiperazine) and © mL Aldrich (S)-(H)-2-methylpiperazine h. Leave the VE for 5 YY. The mixture was heated with 2-bromopyridine and water. And the layers were separated by M ethyl acetate and distributed among the ethyl acetate (YY). The reaction mixture was cooled to [thy] acetate, and the aqueous layer was extracted twice with ethyl acetate using a solution of sodium bicarbonate11. The aqueous phase reaches about

Cir alg solid. Sodium carbonate saturated and sodium bicarbonate saturated twice with ethyl acetate tall and the solution was extracted sodium chloride sodium chloride and the organic extracts were dried after dichloromethane and twice with dichloromethane ethyl acetate and the filtrate was concentrated under Low pressure output Ca Tl 50 + mix it over Te Mevgaf of 1110345 (£00)/z = 71 g of the compound named title (rate 1 (IH H VY 0 =) dd) 77 BH Hummel Tr =] “d) 0.11 delta ((CDs)S0 “(1H nm from “dd) 1.0A “(2H “m) 1 (1H “m) 7 “(3H cm) YY

VA mie (ESI) MS ¢(1H am) A, +A (1H em) V, 88 (1H from A =] «d) T,VV (MAH) ve Example © b

iY 7-instance-; -pyridinyl(Y)piperazinyl])1(methyl) = sar HY imidazole -2-11287-2 methyl-4-pyridin-2-vlpiperazin- 1-ylimethyl}-1H-benzimidazole treated VE 1 g YY (mmol) of example product B in 10 mL of SENN methylformamide N,N-dimethylformamide with 71 g (77,77 mm a) (Use 2 7-chloromethyl-1H-imidazole A 2-chloromethyl-1H-benzimidazole g (l mmol) of cesium carbonate at YY - with stirring for ?0 hours and the reaction mixture was diluted with acetate ethyl acetate JE! and washed 1 times with water and then with brine water; dried over 11:50, filtered and concentrated under reduced pressure. Its concentration ranges from 1-7/) to produce 1778 mg of the compound named with the title in the form of a light yellow solid (Jaa) Production> 167 (melting point 161-144 C 1110008) £00 Lae ((CD5)SO delta hot T= “d) Is (1H am) Y,0F (1H am) YA (3H vac dd) YAY (TH Sa) quilt, 1, for six-cut am) for 14 ad) for VE they are “(1H “m) v.a¢ (1H Vo q but (1H anm)= 0 hana ELA =]” dd) 1 , (tH ra do AES «d) LAC (TH hm (2H am) YOY (IH) perla AeA (BH am) bs (MEH) Yo A mie (EST) MS ¢(1H «bs ) VY, YY “(1H) Theoretical analysis of the formula SC Cu Ns to NO IN TAG TH Practical analysis: GH 9/71 iC Laart GN Carda Y. Example 71 Tahar Y= ( RY -instance-; -pyridinyl (7) piperazinyl](1(methyl)-111-benzimbidazole -(2-1108 2-methyl-4-pyridin-2-ylpiperazin-1-yl |methyl}-1H-benzimidazole example + 7a (867)-"-methyl-1-pyridinyl p)piperazine (3R)-3-methyl-l-pyridin-2-ylpiperazine : blend *.; g I BE (R)-( -)-2-methylpiperazine from Aldrich © 4 ml (0° mol) from

?*-bromopyridine 2-bromopyridine and heat the mixture at VY: VE for an hour. The reaction mixture was allowed to cool to 77°C and distributed between a large volume of ethyl acetate and water. The layers were separated, and another amount of water was added to the ethyl acetate solution for hydration. Then, drops of the HCI solution (1 M) were added to the 2 ethyl acetate/water mixture with vigorous stirring. The layers were separated and then the pH of the aqueous phases, after mixing, was made to reach about 11 using a solution of saturated sodium bicarbonate and solid sodium carbonate. Sodium chloride was added and the German solution saturated with chloroform was extracted.

on a few drops of isopropyl alcohol (its concentration is ½ times). And dried

Ve organic extracts after mixing them over (NaS), the filtrate was filtered and agitated under low pressure, resulting in VA g of the compound named (production rate-(IA)

711 (BH Henl 1 =] “d) 017 MB (0)0)) delta £00) 11 NMR

1,00 am (x dd) “(1H (x 7 (BH am) turn (IH is VY Ye =] “dd)

MS (1H em) A, +A (1H am) V, 29 (1H ful A =) (d) YY (IH from A =] edd)

m (MH) YYA m/e (ESI) Ex 7 "b "- a (87)-7-methyl-; “pyridinyl (?) piperazinyl [)1(methyl)-111-benzimidazole -(28])-2 2-methyl-4-pyridin-2-ylpiperazin-l-ylJmethyl}-1 H-benzimidazole

VA treated g (4.47 mmol) of article product a dea 10 5 ITT

Jie SENN xe formed NN-dimethylformamide at the gonial zero with a solution of 1.7 g (.17 mmol) of 7-chloromethyl-111-benzimidazole and 2-chloromethyl-1H-benzimidazole.

Je 0 from Jia SENN formamide N N-dimethylformamide and after 10 minutes » he was treated

mixed with 0.77 g (51 mmol) cesium carbonate and removed ales by cooling; An hour later, the Baal reaction mixture was diluted with ethyl acetate and washed

ve? times with water, then with brackish water; aa above 01:50, filter and concentrate the lifter under reduced pressure. The ore was absorbed on a silica gel and flashed (by elution) with a mixture of av (Y=) with a concentration of dichloromethane (methanol) in the form of a solid with a color of 1.8 vantage. HNMR $2 10F=10) light yellow (production rate < 774). Melting point (am) is L, A 1 = J (d) 50, L:00) delta Ar «Salas £14) 61714 «(1H «m) Y,AY (1H 1H A =) «dd) AA «(1H 8 "(1H VE =] «d) EV «(1H q only 111 «m) towards «(1H h yE =] «d) (2H em) VOY (IH from AE h od) LAY (IH TE EA = T odd) 0 {(M+H)" 1 m/e (ESI) MS ¢(1H <bs) 177 «(1H em) A, +A «(3H em) 1 0 CN CLA HH VS YY IC CH Ns Formula theoretical analysis

YY NV, oY iH Va Ye iC Action Analysis: ye

YV eg methyl)piperazinyl (1)]-pyridinyl (7){methane (Y) 7-[;-(111-benzimidazolyl) §-N

N-{2-[4-(1H-benzimidazol-2-yimethyl)piperazin-I-yl]pyridin-3-capric acid (methanesulfonamide)

YY Example ve

N-(2-chloropyridin-3-yl)methanesulfonamide ((Y)n-chloropyridinyl)

Od mmol) of ?-chloro-pyridinyl (?) VV) gm 1 mdse at ? m dichloromethane 01 ml of dichloromethane in 2-chloro-pyridin-3-ylamine methane sulfonyl chloride g (54 mmol) of methanesulfonyl chloride YL YY using and after stirring for a period of triethylamine ethylamine DE and 95 μg (13.8 mmol) of 0 h; reaction mixture was diluted with water” layers were separated extracted aqueous phase 8 then organic layers were mixed; dried over dichloromethane twice with dichloromethane filtered The filtrate was concentrated under reduced pressure, the concentrate was absorbed on a gel (MgSO, wet hexanes: Jay acetate hexanes) and flashed (by volatilization with a silica acetate fluid of 7/7 ml of VY hydroxide solution); low pressure and was added to the ve solution vigorously for about a night (oT Bg .70 its concentration is Sle sodium hydroxide sodium

AA

the solution to a pH of about 1 hour until it becomes homogeneous. then 8 caliber; Saturate with 110:50 and extract © 1 times with ethyl acetate, the concentration of which is NaCl, not with hydration. The extracts were dried after mixing them over 3050 filtrate, and the filtered acetate was filtered under low pressure, resulting in 1.0 g of the compound called the title.

Tetrahedron Letters 38, 26, 4667-4670, in ref. ela (production rate-97/). See delta ((CD3),S0 MHz; 0 ('H NMR n.t. J. Org. Chem. 2000, 1263-1270 ¢1997 (1H H NMR dd) VAY (IH is AE rub =] odd) 15 (3H) (J 7 . (11) 011 mie (ESI) MS ¢ (1H bs) alpha (1H dart 0,£) =J “dd) AYY B1 Example N-(2-piperazin-l-ylpyridin-3- pyridinyl (?)) 11.75 piperazine Mix 8.7 g (1007 mmol) of piperazine, heat n-butanol mmol) of example product 1?a and 956 mL of p-butanol (AYER) and concentrate under pressure a YY Mix with rewind for © days. The reaction mixture was left to cool to flash (by liquefaction with a mixture of 77 percent of low silica. The concentrate was impregnated on a ve acetic acid silica gel with dichloromethane / dichloromethane acetic acid. HNMR (AN ss production) Jane) gram of the compound named with title 1 in proportion (1) produced each (3H es) YOY ((CHCOH) from CH; (e) 0.59 delta (CD; 0D megahms ‎ Tov)

ANY (TH HEN AE HQ add) V,VA (IH H A rub =] dd) 07 «(8H «m) (M+H)" YoV m/e (NHyDCI) MS ¢(HY DR PH =] “dd) v.c71 methyl methyl)piperazinyl (1)]-pyridinyl (7){methane (Y)-(111-benzoimidazolyl[1-7] IN Nimbed sulfur - Hasa Abram [Iber-A 010:21(7!<-111-66021011201-2)-4]-11-12 yl}methanesulfonamide gm 1717 VY mmol) from a methionine TY) mix 055 g Yo methyl SENN in ?mL of cesium carbonate (5 mmol) of cesium carbonate

YAYA aq for © minutes. Then the mixture was treated with oT Tag - YY at NN-dimethylformamide formamide (mmol) of ?-chloromethyl-111-benz imidazole +, TY) using 075 g of the reaction mixture under pressure 37S 111 -0020-Ata2-2010:006. After one hour, silica 1206 was flashed and impregnated on low silica gel. The ore was drank on a silica gel, chloromethane, methanol, from Michael 701, and flashed (by liquefaction with a mixture of 1 percentage of the compound called the title (production rate - 1.7).

FOYT (BH es) VOY (4H em) 16 delta (CD), SO megahaklen (MH) 'H NMR Arla (1H from AS q =) dd) fer (2H (z) ©, Ve «(2H (e ¥,V) (4H in definite) (1H from V,0 =J ¢bd) V,0V (IH) V,2 =J bd) ) V,£¢ «(2H mle (EST) MS ¢(H) ebs) AY (IH mle 1 h «dd) A, +A (1H lm 1 h) dd) 0 0

AM+H)" YAY

YA Example 2-)]4-6- (?)) piperazinil (1)]-methyl (-111-benzimidazole i psp ET) = 1177 fluoropyridin-2-yl)piperazin-1-yl] methyl}-1H-benzimidazole

YA example vo 2-chloro-3-fluoropyridine ?- fluoropyridine - 5 IS OVA treated m(0,)gm© (Use of 10 4-diaza [YY] dioctane 1,4-diazabicyclo[2,2,2]octane in 111 mL of ah diethyl ether jil point B 10?mL (5 51 mmol) of Kec lithium n-butyllithium (a solution of 0.1 To molecular concentration in hexanes at -0 C. Then the reaction mixture was pressurized to -0 C for one hour and then re-cooled to -74 C. The re-cooled mixture was treated b © g (2,00 mmol) of 7-fluoropyridine 3-fluoropyridine in 2 ml of diethyl ether drop by drop After stirring for two hours at -74 °C, the mixture was treated with VY g (° in mmol) of hexachloroethane in ; ml of tetrahydrofuran, and after stirring for one hour at A below zero, the reaction mixture was treated with a solution of 15 ml of water and 1 ml of VATA tetrahydrofuran.

Ve minutes, the amount of 00 reaction mixture was added to zero percentile and after 4) tetrahydrofuran LL was added to the mixture. The layers were separated, additional diethyl ether was extracted from water and diethyl ether, and the diethyl ether ul ethyl Sy layers were dried. The aqueous phase was filtered twice under Ge Sys pressure, after mixing it over 10:50, ethereal layers were filtered and flashed (by elution with a mixture of low silica acetate). (7) yielded 7.8 g of the compound called acetate JY! (1H am) 0.66 delta ((CD5),S0 «alga Yoo] HNMR (707 = z yl) with title (modified)

J(Na + M) 1014 mi (ESI) MS (HY am) AY) (1H em) 5

GOYA Example 1-(3-fluoropyridin-2-yDpiperazine piperazine )) Y) 7-Fluoropyridinyl (1 ve ml of p-butanol Vor at 78 Jad) from (Use +10 YO) was treated with 7.70 g, then succumbed with piperazine (g (° l mol) of 71.5 mM piperazine at n-butanol and concentrated under reduced pressure. a YY Rewind for © days. And let the reaction mixture cool down to Separate the ethyl acetate solution and the concentrate slurry using water and ethyl acetate evaporate under reduced pressure resulting in ATS leaching Na,SO; Above “a 8x” ethyl acetate Ve pla 500( TH NMR (ZY = z Lay) g of the named compound (YF modifier)

V,4A (TH em) LA «(1H em) LAE (4H em) HA (4H em) ¥,A delta ((CD;),SO (M+H)" YAY m/e (ESI) MS ¢(1H «m) Ex. 3-fluoropyridin-2-yl)piperazin-1-ylJmethyl}-1H-benzimidaiole g (7.5 mmol) EA caVA Mix 8 g (?71 mmol) example product with 2 g -chloromethyl-IH-benzimidazole from 7-chloromethyl-1111-benzimidazole methyl SENN mL of YA in cesium carbonate (0.07 mmol) h; concentrate the mixture under pressure Low 0.76 sad formamide at 77 °C, stirred ve, removed .701 dichloromethane, and washed with a mixture of methanol (16000 / dichloromethane)

YAYA

Vey the solid by filtration and concentrate the filtrate under reduced pressure. And the ore was impregnated on a gel 7.0 flash (by elution with a mixture of silica and fluorescence) and impregnated on silica gel silica 1 mg of compound 1 ph (dichloromethane of methanol 00612001 / dichloromethane

HNMR M 717-701 Melting Point (AF Labeled Title (Production Rate-) 2H through (J) 4H (h 7 (4H em) Y,1Y (00? megaphn 0 qt) delta 0 m/e (APCI) MS ¢ (1H em) Nick «(3H «m) Arla «(2H em) Ara (IH em) TAY (MVHH)” YAY

YV,4A (only £0.940 tH €1E,) e: CH gFN50.4H,0 Theoretical analysis of the formula

JYY,40 oN for another GH 11.15 iC Practical analysis:

Ya Ext. 01 (¥) piperazinil (1)]-pr diol (Jie (71)-benzimidazol and Lyl 111-41-1 6-[4-(1H-benzimidazol-2-ylmethyl)piperazin -1-yl]pyridin-3-ol ya Example 5-(benzyloxy)-2-chloropyridine ©-(benzyloxy)-?-chloropyridine -8-hydroxypyridine ys IY mmol) from 01 (? 6 g vo g !mmol) was treated with cesium carbonate V,Y and 2-chloro-5-hydroxypyridine .benzyl bromide ml of benzyl bromide 1.5 DMF ml of A in cesium carbonate the celal temperature was set and after stirring at 77 m for 7 hours; The reaction mixture was acidity reduced to 7 using saturated aqueous 101:00, and extracted with dichloromethane (Workshop (cn TA) » 0:50, organic extract over uss dichloromethane Ye (CHCl), filtrated under reduced pressure. The ore was purified by chromatography. Abductor (exported in g of the compound labeled with the title as a white solid (modified TEE Vintage MS §(CHLCL) +f = (Rg) yield -< 7974). Melting point > 0ºC; flow rate (= No =J 11 “d) AY delta ((CD3,SO mbg Yo +) 11118 ¢ (M+H)'YY + (2H each (Y) (6H em) shaking ) “to make Y,V k =] “1H” dd) V,00 0 Example 9 "b

VY tert-buty 4-]5-neth-butyl taliscoperic-1-nizarbib [(Y) ?-[©- (benzyloxy)pyridinyl (benzyloxy)pvridin-2-yl]piperazine-1-carboxylate VAY g of example product 95 ?Aa?, 0 g of Pdy(dba); £0, + g of racemic BINAP; VT g of sodium tert-butoxide butoxide and 4.41 g of 1 pl ° -th-butyl carboxylate 00 ml Atert-butyl piperazine-l-carboxylate of toluene pT Ag toluene at 5: for ? hours.The reaction mixture was treated with 50 ml of toluene 1010608 and 001 ml of diethyl ether and washed the mixture with water and dried the organic phase over 00:90 filtered and concentrated the filtrate under low pressure, and the ore was diluted by flash chromatography, by liquefaction with a mixture of ethyl acetate Ve ara/hexanes in a ratio of 5:1 yielding 4.0 g of the compound named with the title (yield rate < 747), melting point 44-47 °C, flow rate -1.71 (using a mixture of ethyl acetate pyridin/hexanes by :£(¢ 0 MS "lbs. Example 74g 1-[5-(benzyloxy)pyridinyl(7)]piperazine 1-[5-(benzyloxy)pyridin-2-yl [piperazine] 1,176 g of example product 9b was treated with 7.5 ml of trifluoroacetic acid with stirring at ? m for two hours. The concentrate was distributed between a mixture of 100 ml of: A8/011:0 ml of p-butanol, neutralization and a mixture of 5400 ml of water/ml of 1. and separation of the organic phase; It was dried over NaS, filtered, and the filtrate was concentrated under reduced pressure yielding the compound named as the title in the form of a white powder. Use in the © - next step without further purification. Example 4 ] piperazinyl {(V)methyl)-111-benzimidazole 2-({4-[5-(benzyloxy)pyridin-2-yl]piperazin-l-yl} methyl)-1H-benzimidazole mg of 7-chloromethyl -111-benzoimidazole AA Example product mixed 49 g and ml of triethyl 0 © [DMF] 1 ml of 1 was dissolved in a mixture of 2-chloromethyl-1H-benzommidazole Yo ml of Yo The mixture was treated with (oie Le m) for a period of YY and after stirring at triethylamine Abelamine

YAYA

Acetonitrile then entrapped for 4 ? hour. The reaction mixture was distributed between a mixture of 100 mL of O[CHCl] mL of n-butanol and a mixture of 800 mL of water/©mL of 101,011. separation of the organic phase; Dry over 0.380:50, filter and concentrate the filtrate under reduced pressure. The ore was purified by flash chromatography, yielding 1,174 g of 0 - the compound named as the title as a white solid (rate = z Lay 755). melting point 4-77 m; Flow rate - 1,776 (using an 8:48 mixture of [CHCl NH,OH :methanol concentrate] ),+7(¢ Yoo) TH NMR ¢ (MAH) 400 ms ms (1H em) V,00 (5a ¥ =J «IH »d) 0.50 (1H «NH ¢bs) 17, Lh ((CD;),SO amL «d] TA «(2H cm) V,\o “(8H “m) and =J 4 Hz) e 0,.0 (vv “(2H 0 (2H 1)” Tflh)© Hamza t) Y,0V turns J = 8.1 Hz). Jud 79 H 41-7 -(111-benz emy daz and lyl)7 (methyl) piperazinyl (1)]-pyridinol (©) 6-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1- vl]pyridin-3-ol

800 pale of the example product 19D in 75 ml of ethyl acetate was treated with 5 mg of palladium ys carried on a carbon ratio of 1/7 under a cover of hydrogen gas at 7 °C until Ja thin-layer chromatography on raw material consumption; The mixture was removed by filtration and the filtrate was washed with methanol and :011:01. The filtrate was mixed and concentrated under reduced pressure. The ore was purified by flash chromatography (by denaturing with a mixture of A011:0: methanol NH,OH methanol 1:10:46 YL) yielding 2765 mg of the compound called the title in the form of a pure white solid (modifier = z Yl 797.) Melting point 145-144 5 Efficiency rate < 0.08 (using an 86:8 mixture of NH,OH methanol Jl Sie:CH,Cly concentration: for 0 01 MS Yoo) 11 NMR ¢ (M+H)" megamens "d) V,YY Gl (CH;0D 111 L - Y,¥ Mz) Arla "(2H <m) but 2 no =J "1H" dd) 4« 7 shake) = J «1H «d) 1,Yo 1 shake)

Yo d (2H s) 60 ¥ 0 tel lahar hamza until 0 3 =J (0 hz); YAYA

Vet binary (8 Sa 0.1 00808001 eq. methanol 0 ) Ci7HoNs;O Isotopic analysis of formula 1 for CUIA GH AY YC (dichloromethane chloromethane tH 17.6:0 Practical analysis: 010 Ex. > methylpyrdin-2-yl)piperazin-1-yl}methyl}-1H-benzimidazole

JET) The compound named with the title can be prepared following the procedure of Example 7 using 1-(lidemirib-7) instead of 1-G3-methylpyridin-2yDpiperazine 1-(2-pyrimidyl)piperazine. Piperazine 1 In Vivo Data Rat Penile Erection Model As primary animal models for the study of Wistar erection, Wistar rats were used in vivo. All experiments were conducted between the hours of nine in the morning and three in the afternoon in a test room diffused with red light. The rats were weighed and left to adjust in a precise room before the start of the experiments. The rats were placed separately in transparent cages Te sad the test © cm after the injection of the drug. The number of penile erections was recorded by monitoring 7,717,710 dimensions per minute after the administration of the drug dose. The number of animals that showed direct erection of 010 duration or more was recorded and expressed as the percentage of incidence. The compound ?-[(?-pyridinyl ve 2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1H-benzimidazole

YAY A

Veo for penile erection in rats

Yo excipient i

Ta 1 in saline (concentration (D)-ascorbic acid) (1)-ascorbic acid (1)-ascorbic acid was used in an animal per dose. VY apomorphine was used and vehicle as excipient (Jef pile µmol/kg) resulted in Induced an erection in the penis of 1.1 as a positive control with a dose of

AY of the rat with a percentage of methyl]- (1) that 7-[(?-pyridinyl (7) piperazinil 1) and the data appear in the table

Coa 2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1H-benzimidazole imidazole iH) 0.11 statistically significantly increased penile erection in rats after being given doses ranging from μmol/kg under Skin. 1.1 μmol/kg to 7 Table 1 (©) Pyridinol [1] Compound inductance £177-(111-benzimidazolyl (7)methyl)piperazinil 6-[4-) 1H-benzimidazol-2-ylmethyl)piperazin-1-yl]pyridin-3-ol for penile erection in rats

YAYA

1 1 (concentration of saline in saline (L)-ascorbic acid (1)-ascorbic acid was used as a control animal apomorphine per dose. Apomorphine VY mg/ml was used as an excipient. He used micromol/kg, which led to a positive 011 drawbar erection at a dose of

AY ratio and the data in Table 7 shows that 1-76[-(111-benz-imidazolyl (7)methyl) piperazinil

Cua 6-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1-ylpyridin-3-ol (¥)piperidinol](1)

G0) penis erection was statistically significantly increased in rats after doses ranging from 1 micromol/kg subcutaneously. From about 85009 micromoles/kg to 15 0 the incidence of not less than 0 micromoles/kg. 1 about Bm ferrets (body weights) male Fitch ferrets obtained on male animals stinking ferret and fasted overnight by Marshall Farms and 1,9 kg) of Marshall Farms 0.1 range or compound according to the present invention under apomorphine subjected to experiments. Animals were placed individually in control cages and vomiting and signs of drug-induced nausea were identified (by direct observation) for a period of 90 minutes after drug injection8. And the animal cleans its stomach area vigorously.These regurgitations were preceded by vomiting and burping.i Established by frequent abdominal contractions coupled with ye 0 table methyl]-111-benzimidazole (1) piperazinil (1) urging 7-[(4-pyridinyl 2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]- 1H-benzimidazole for vomiting in rats

YAYA

b - Use sterile saline solution as an excipient. Six animals were used for each dose. Apomorphine was used as a positive control in Table © at a dose of #0 μmol/kg resulting in a TE of ferrets by Ye and as shown in Table © dis EY (7) piperazinil did not induce (0) ° Methyl]-111-benz 2-[(4-pyridin-2-ylpiperazin-1-yl)methyl}-1H-benzimidazole Js aad vomiting in ferrets after subcutaneous administration. Apomorphine has been used. apomorphine was used as a positive control in these studies.These data demonstrate that 7-[(;-pyridinyl(7)piperazinyl) “HO[dia (1))-benzimibazole 2-[(4-pyridin-2-ylpiperazin-1-) ylymethyl]-1H-benzimidazole gave ye a noticeable advantage over apomorphine in that it JT gu induced penile erection without inducing vomiting. Compounds of the present invention can be used, particularly -[(;-pyridinyl(Y)] Piperazinil (1) methyl]-111-benzimidazole-111-[epta-zap 1 2-[(4-pyridin-2-ylpiperazin-cbenzimidazole) with phosphodiesterase antagonists (©) 5 Lay phosphodiesterase in ‎ “lly ve to name a few; sildenafil or vardenafil as a way to treat sexual dysfunction in my breasts. The Gy compounds of the present invention may be used; and in particular 7-[(;-pyridinyl(7)piperazinyl)(1)methyl]-111-benzimidazole 2-[(4-pyridin-2-ylpiperazin-1-ylymethyl]- 1H-“benzimidazole with an excitatory adrenergic receptor antagonist, including but not eas 7 terazosin, prazosin, or tamsulosin, as a method of treating gynecomastia sexual dysfunction. -[[?-pyridinyl (7) piperazinyl ())1(mel]-111-benzimidazole 2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]- 1H- YAYA

08 eg but not limited to duu with a dopaminergic agonist; Including cbenzimidazole as a way to treat breast sexual dysfunction. apomorphine

compounds according to the present invention; Especially 1-[(?-pyridinyl (7) piperazinyl) 1(methyl]-111-benz imidazole “2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1H- benzimidazole is a 0 dopaminergic agonist and therefore useful for the treatment of sexual dysfunction in (LY) ADHD; Alzheimer's disease; drug abuse; Parkinson's disease; anxiety; schizophrenia; mood disorders and depression as described in ref. receptor: a controversial therapeutic target.

N.J.Hrib.

Drugs of the dopamine 'future 25:587-611 (2000) Dopamine and sexual behavior.

M.

Melis and A. ¢Argiolas.

Neuroscience and Biobehavioral Reviews 19:19-38 (1995) 01 Dopamine receptors: from structure to function.

C.

Missale, S.R.

Nash, S.

Robinson, M.

Jabber and M

.Caron.

Physiological Reviews 78: 189-225 (1998) and compounds according to the present invention; Especially 1-[(?-pyridinyl (7) piperazinyl) 1(methyl]-111-benzimbidazole-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1H-benzimidazole They are dopaminergic agonists and therefore useful in the treatment of cardiovascular disorders.It has been demonstrated that dopamine and dopaminergic agents exhibit pharmacologically significant cardiovascular effects on blood pressure and heart rate and may be useful in the treatment of cardiovascular disorders (see the following In Chen FF, and Lin MT, Effects of dopamine, apomorphine gamma-hydroxybutyric acid, haloperidol, and pimozide on reflex bradycardia in rats, Journal of Pharmacology and Experimental Therapeutics (1980) 214: 427- A 2 ) It has been stated that preliminary data supports the potential clinical benefit of dopamine receptor agonists in the treatment of heart disease ai) Ses Hahn, RA and MacDonald BR, Primate cardiovascular responses meditated by dopaminine receptors: effects of N,N-dipropyldopamine and LY 171555, Journal of Phamacology and Experimental

(Therapeutics (1984) 229: 132-138 vo

‎VATA

Ved (0)-pyridinyl (7) piperazinil IY and the compounds according to the present invention, in particular “2-[(4-pyridin-2-ylpiperazin-1-y)methyl]-1 H-benzimidazole imidazole yu H) methyl]- contains dopaminergic agonists and is therefore useful in treating inflammation. The agents may appear to be beneficial in anti-inflammatory effects.

Bendele AM, treatment of diseases in which inflammation plays a detrimental role (see reference oe

Spacthe SM, Benslay DN, and Bryant HU, Anti-inflammatory activity of pergolide, a dopamine receptor agonist, in Journal of Pharmacology and Experimental Therapeutics (1991). -5

Lissoni P, Mandala M, Giani L, Malugani F, Secondino (see reference for cancers).

S, Zonato S, Rocco F, Gardani G, Efficacy of Bromocriptine in the Treatment of Metastatic 01

Breast Cancer and Prostate Cancer-related Hyperprolactinemia, Neuroendocrinology Letters (2000) 21: (405-408) As used herein, the term 'agonist' refers to a class-affected compound that induces a dopamine receptor chemical response to one or more of Dopamine receptor classes ve Substance dopamine-like Measurement of response with respect to dopamine 0 Visible intracellular vitality Totally excitatory The term “pharmaceutically acceptable carrier” when used in this statement means an adjuvant For encapsulating material a diluent filler of any kind which are all non-toxic; inert solid; semi-solid or liquid formulation auxiliary 0. Some examples of materials that may act as pharmaceutically acceptable carriers are materials

Jie starches ¢ sucrose and sucrose glucose glucose clactose lactose sugar Jie carboxy Jie and its derivatives cellulose cellulose ¢ potato starch potato starch corn starch Lis ethyl cellulose cellulose J ¢sodium carboxymethyl cellulose ¢malt ¢powdered tragacanth tragacanth powder tcellulose acetate and cellulose acetate Ye filament waxes cocoa butter cocoa butter Jie excipients excipients fale talc ¢ gelatin

VY cottonseed epeanut oil peanut oil Jie 50000511017; oils 95 corn oil colive olive oil sesame oil ©100; _sesame oil oil safflower oil coll propylene glycol Jie sglycols glycol compounds ¢soybean oil and soybean oil com oil tethyl laurate and ethyl oleate Joy! such as oleate esters tpropylene glycol esters such as magnesium hydroxide buffering agents pH regulating agents agar agar 0 alginic acid taluminum hydroxide and aluminum hydroxide magnesium hydroxide isotonic brine tpyrogen-free water i asl from JB Generators; Water 10 and buffer solutions ethyl alcohol ¢Ringer's solution tisotonic saline lubricants plus phosphate buffer solutions for pH and other suitable non-toxic sodium lauryl sulfate such as Sodium lauryl sulfate Ve antifouling Jol so ccoloring agents In addition to coloring agents Cmagnesium stearate Magnesium local agents; Flavoring and scented coating agents; releasing agents for adhesion; preservatives; csweetening, flavoring and perfuming agents may also be present in the composition; According to the decision of the composition preparer. Antioxidants and antioxidants The present invention provides pharmaceutical compositions comprising compounds according to the present invention ve pharmaceutically acceptable non-toxic one or more. Pharmaceutical compositions dala can be formed with parenteral in solid or liquid form; for non-enteric injection oral administration rectal administration or for rectal administration injection sald The present invention also includes within its scope pharmaceutical compositions comprising one or more dopaminergic substances prepared and formed in combination with a pharmaceutically acceptable non-toxic composition ye one or more. Pharmaceutical compositions for oral administration may be formed in solid or liquid form; ad) for non-enterial or for administration via The pharmaceutical compositions according to this invention may be administered to humans and other mammals by non-enteric route poi all by sublingually Sublingual pil route Intravaginal dintraurethrally Intraperitoneally cintracisternally Intrapelvic parenterally vo (in powder form topically topically cintraperitoneally intraperitoneally cintravaginally

11 or as a spray bucally by cheek “drops or ointments + ointments” 5 The term “non-enteric” indicates; when used in this coral or nasal spray, oral or nasal Intramuscular, cintravenous, the statement refers to methods of administration that include intravenous injection, intraarticular, subcutaneous, intraperitoneal, intraperitoneal, dntramuscular, infusion, and intraarticular 2 infusion.

The preferred method of administration in humans is orally or sublingually. Pharmaceutical compositions according to this invention for non-intestinal injection include solutions, dispersions, acceptable ina sterile aqueous or anhydrous emulsions, and sterile powders for reconstitution into sterile injectable solutions or dispersions. 0 ahd includes carriers; diluents; suitable aqueous and anhydrous solvents or excipients cele ethanol cethanol polyhydric alcohols polyols (propylene glycol polyethylene glycol glycerol suitable mixtures of 4 Cu (Jie) olive vegetable oils) and injectable organic esters such as ethyl oleate and appropriate fluidity can be maintained; by the way; By using an encapsulating substance such as lecithin, decithin, by maintaining the required particle size in the case of dispersants, and by using stress-reducing agents.

.surfactants

These compositions may also contain auxiliary materials Jie adjuvants Gila agents Wetting agents Wetting agents Emulsifying agents Dispersing agents Y. Protection from the influence of microorganisms can be ensured by antibiotic agents There are many antibacterial agents and antifungal agents, such as JO, cparabens, chlorobutanol, phenol, sorbic acid, and the like. It may also be desirable to have Isotonic agents, eg sugars, sodium chloride, etc. Ye Long-term absorption of the injectable pharmaceutical form can be induced by the use of buffering agents.

VAY aluminum monostearate (Jia) delays absorption; For example .gelatin and gelatin and in some cases. to prolong the effect of a drug; It is often desirable to slow down drug absorption subcutaneously or intramuscularly. This can be achieved by using a liquid suspension of asia at 0 0 a crystalline or amorphous material with poor solubility in water. Hence, the absorption rate of 0 and the crystal size of the drug depends on its solubility rate, which is; turn; Depends on the size of the crystal. Delayed absorption of a drug composition given via Gest and alternatively; crystalline form non-enteric by dissolving or suspending the drug in an oily excipient. suspending Suspensions may contain; In addition to active compounds on ethoxylated isostearyl suspension agents, for example. Etoxyl isostearyl alcohols (Jie cagents Ve) and sorbitan polyoxyethylene sorbitol polyoxyethylene sorbitol esters calcohols aluminum metahydroxide microcrystalline cellulose microcrystalline cellulose esorbitan esters tragacanth agaric cagar-agar agar bentonite metahydroxide and mixtures thereof, and as desired; and to obtain a more uniform distribution, the compounds of the present invention can be incorporated into ial slow-release systems or targeted-delivery systems such as polymeric primers. cpolymer matrices liposomes and microspheres which can be sterilized, for example (Ja) by filtering through a bacteria-retaining filter or by incorporating sterilizing agents in the form of sterile solids 0 which can be dissolved in sterile water Or a sterile injectable medium AT immediately prior to use The compounds of the present invention may also be in the form of flour coatings, if appropriate With one or more excipients as mentioned above Solid dosage forms may be prepared from tablets ctablets cdragees Capsules Grains epills and granules granules with aaled coatings and coverings shells such as enteric coatings Yeo release controlling coatings and other coatings are well known in dd formation Pharmaceutical compositions. In such solid Sle forms the active compound may be mixed with a diluent

1

At least one is inert, such as sucrose, lactose, or starch. It may also include such dosage forms; as usual application; on additional substances other than inert diluents; che lubricants for tablet making and other tablet making auxiliaries such as magnesium stearate and microcrystalline cellulose. In the case of capsules, tablets and pills, dosage forms may also include pH-regulating agents. They may optionally contain opacifying agents and may also have a composition such that they release only the active ingredient(s) or preferably; in a specific part of the intestinal tract in a delayed manner. Examples of combined compositions that may be used include materials

Polymers and waxes.

1 Stocked injectable forms are prepared by forming micro-encapsulated base materials from the compounds of the present invention into biodegradable ALE polymers Jie polylactide-polyglycolide and depending on the ratio of the compounds according to the present invention to the polymer and the nature of the polymer. selector used; The firing rate of the vehicles can be controlled according to the present invention. Examples of other biodegradable polymers include SL (ester) polymers.

poly(orthoesters) 12 and poly(anhydride) (7)0170:085a0pm. Buffered injectable formulations are also prepared by restricting the drug to liposomes or micro-emulsions suitable for body tissues.

Injectable formulations can be sterilized; For example; By filtering through a filter that traps bacteria or by incorporating sterilizing agents in the form of sterile solids that can be dissolved or

x. Dispersed in sterile water or another sterile injectable medium immediately before use.

Injectable formulations can be formulated; For example, sterile aqueous suspensions or

injectable oil; According to known technology using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be a solution; suspension or emulsion

An injectable sterile in a non-toxic diluent or solvent acceptable for administration by non-enteric route eg

Yo is a solution in Gls 10 Diol A1,3-00180600. Among the acceptable excipients and solvents that may be used are water ¢ Ringer's solution according to the US Pharmacopoeia YAYA

1

The sodium chloride solution is isotonic. In addition ; Sterile fixed oils are usually used in the form of a solvent or suspension. For this purpose, any fixed oil can be used, Le bland fixed oil, including synthetic mono- or 5-glycerides. In addition; Jie fatty acids are used

acid ° 0161 in the preparation of injectable compounds. Solid dosage forms for oral administration include capsules; tablets; pills; powders and granules. In solid dosage forms of this Jail, the compound or compounds of the present invention are mixed with at least one pharmaceutically acceptable inert excipient or carrier Jie sodium citrate or calcium phosphate and/or { fillers or Extending materials (Jie extenders ve starches; lactose clactose sucrose csucrose glucose glucose mannitol and silicic acid B binders materials alkylated carboxymethyleellulose compounds alginate cgelatin 80s calginates epolyvinylpyrrolidinone sucrose and acacia tacacia c) humectants Jie humectants glycerol tglycerol 2) disintegrating agents ie disintegrating agents agar- Vo agar cagar-agar carbonate Calcium Las calcium carbonate Potatoes or tapioca Alginic acid supports Certain silicate 5; sodium carbonate 'carbonate e) Jal se Solution retarding agents such as paraffin;? and absorption accelerators Jie absorption accelerators ¢quaternary ammonium compounds g Wetting agents such as cetyl alcohol x. 'glycerol monostearate 7' Ja absorbents kaolin clay tentonite clay < u sind 5 kaolin clay f + lubricants Jie dale talc calcium stearate magnesium stearate pli solid esolid polyethylene glycols sodium lauryl sulfate 58a” and mixtures thereof. In the case of capsules; Tablets and pills may include a dosage form

Yeo also contains pH-regulating agents. YAYA ye as a filler in Blas capsules. Solid formulations of the type filled with a soft and solid substance can also be used using excipients such as lactose, gelatin capsules, polyethylene glycols (ld) or milk sugar in addition To high molecular lactose polyglycols and the like.

2 Solid dosage forms may be prepared from cal BY dressings; capsules; Pills and granules with coatings and coatings such as enteric coatings and other coatings are known (Tas) in the technology of forming pharmaceutical compositions. They may optionally contain bloating agents and may also be of such a composition that they release only the active ingredient(s); or preferably; In a certain part of the intestinal tract Intestinal tract in a delayed manner. Examples of combined structures that may be used include:

0 polymeric materials and waxes.

Liquid dosage forms for oral administration include lozenges; microemulsions; solutions » suspensions; Syrups and elixirs are pharmaceutically acceptable. In addition to the compounds of the present invention; Liquid dosage forms may contain inert diluents commonly used in the Jie technique eg; Water or sal solvents Dissolving agents and emulsifiers such as alcohol

ethyl alcohol isopropyl alcohol alcohol ENRM 50; ethyl carbonate cethyl acetate benzyl alcohol cbenzyl alcohol benzyl benzoate propylene glycol “VJ Sule propylene glycol 7’-butylene 1,3-butylene dimer “dimethylformamide” oils (in particular those of cottonseed, peanut, maize, seed, olive, castor, and sesame); glycerol 81760:01; alcohol

OL) Polyglycol compounds cretrahydrofurfuryl alcohol Tetrahydrofurfuryl Te and sorbitan mixtures of sorbitan fatty acid esters and polyethylene glycols fatty acid esters thereof.

and to ula inert diluents; Oral formulations may also include adjuvants such as wetting agents; emulsifying and suspending agents; local factors; Flavored and fragrant.

transdermal Dosage forms for topical or transdermal administration include lotions ccreams pastes according to the invention ointments pastes Sj administration

1

gels; powders; solutions»; atomizers»; Inhalants or patches Active Ingredient Mixes in sterile conditions with acceptable Jala Wana and any required preservatives or buffer solutions as appropriate. This invention also includes in its scope ophthalmic formulation ¢ ear drops ear ointments; Powders and eye solutions.

; Ointments may contain; pastes; creams and gels; In addition to the compounds of the present invention; contains excipients such as animal and vegetable fats; oils; candles. Paraffins “paraffins” starch tragacanth ctragacanth cellulose derivatives ccellulose polyethylene glycols epolyethylene glycols silicones lS ye silicones bentonite cbentonites silicic acid acid 5:1:616” tale and zinc oxide zinc oxide or mixtures thereof.

1 Powders and sprays, in addition to the compounds of the present invention, may contain excipients: Jie, lactose, dactose, dale, silicic acid, aluminum hydroxide, calcium silicate compounds, and polyamide powder. powder or mixtures thereof. Aerosols may additionally contain common propellants such as CFCs and CFCs.

.chlorofluorohydrocarbons Vo

The compounds of the present invention can be used in the form of acceptable salts (Us) derived from

inorganic or organic acids. The term “pharmaceutically acceptable salt” means Gla a

“acceptable salt” are those salts which, within the scope of good medical judgment, are suitable for use in contact with tissues of mammals, particularly humans, without producing a toxic irritant response;

vs harmful sensitivity etc. and commensurate with a reasonable risk/benefit ratio. Pharmaceutically acceptable salts are defined as Tas in the technique. for example; describes s. Mother. SM.Berge and collaborators

Pharmaceutically acceptable salts are detailed in reference .J.

Pharmaceutical Sciences, 1977, 66: 1 et seq The salts can be prepared in situ during the final separation and purification of the compounds.

free base of the invention or separately by reaction of a shot base functional group (ad

aes as function Yo is a suitable organic. Examples of salts in addition to (PAA) include but are not limited to acetate adipate cadipate alginate calginate citrate ke

No aspartate benzoate lg Hu caspartate benzene sulphate AUD cbenzenesulfonate sulfate cbisulfate butyrate butyrate camphor ccamphorate camphor sulfonate SUD gluconate digluconate glycerophosphate 6 rp cl pS chemisulfate Heptanoate cheptanoate chexanoate fumarate hydrochloride ¢hydrochloride ° dihydrochloride trihydrochloride ctrihydrochloride hydrobromide chydrobromide hydroiodide 7-hydroxyethanesulfonate (acethiones) 2- hydroxyethansulfonate (isethionate) lactate clactate maleate methanesulfonate nicotinate cnicotinate-2-naphthalenesulfonate oxalate e; pamoate cpamoate pectinate ¢pectinate persulfate cpersulfate 01 1-phenylpropionate 3-phenylpropionate spools picrate pivalate cpivalate propionate p10031m0m succinate csuccinate sulfate csulfate di(tartrate) ) cbis(tartrate), tartrate (L) ctartrate tartrate “(L) tartrate (L)) tartrate) bis((L) (D) tartrate) tartrate” ( D) tartrate binary (D) tartrate) (DL) <bis((D) tartrate) tartrate “(DL) tartrate binary (DL)) tartrate) ¢bis((DL) tartrate meso-tartrate meso-tartrate di(meso-tartrate) cbis(meso-tartrate) thiocyanate cthiocyanate phosphate glutamate cglutamate bicarbonate cbicarbonate p-toluene sulfonate m-toluenesulfonate and undecanoate. The preferred pharmaceutically acceptable salts according to the present invention are (D) tartrate (LD) 5 “bis((D)tartrate) SLD bis((DL)tartrate ) (bromide) ¢bis(bromide) Y-Di(sulfate) (©015)901131; bis(phosphate) fumarate and tris(hydrochloride) The most preferred pharmaceutically acceptable salt Gy of the present invention is (L) tartrate .bis ((L) tartrate) represents the term 'pharmtically acceptable prodrug' or 'prodrug' when used in this statement; These drugs are AN compounds of the present invention which are; within the scope of good medical judgment; suitable for use in contact with mammalian tissues; especially humans; without triggering YAYA

a

Somaya; irritability harmful allergy and the like; commensurate with a reasonable risk/reward ratio; and be effective for their intended use. Prodrugs can be converted from compounds according to the present invention in vivo into compounds according to the present invention; JB by means of hydrolysis in blood 0 A full description is provided in ref. Higuchi and V.

Stella, Pro-drugs as 1. “Novel Delivery Systems, V. 14 of the A.C.S.

Symposium Series° and reference, Edward B.

Roche, ed., Bioreversible Carriers in Drug Design, American Pharmaceutical Association and (Pergamon Press (1987) For example, compounds of formula (I) that carry an alkoxycarbonyl substituent at Re Alkyl Ji alkyl calkylcarbonyl aryl carbonyl carylcarbonyl alkyl cyclocarbonyl osmotaim pawaldmonro; heterocyclic Ve carbonyl heterocyclecarbonyl or carbonyl (22) (NZ Za)carbonyl are prodrugs. Especially the formation of compounds? H-benzimidazole-1-carboxylate | ¢ H-pyridinyl ((Y) piperazinesyl) 1 (( methyl-1-] (pyrrolidinyl (V) carbonyl)-HY 3 imidazole 2-[(4-pyridin-2-ylpiperazin-1-ylmethyl]-1- (pyrrolidin-1-ylearbonyl)-1H-benzimidazole Ve and ENN mel-?-g(( ; -pyridinyl (Y) Piperazinil N,N-dimethyl-2-[(4-pyridin-2-dimasopric-1-lozadime) HY [die ((V) ylpiperazin-1-yl)methyl]-1H-benzimidazole- 1-carboxamide are typical examples of prodrugs

Compounds in formula (1) and the term “acceptable ester” lana or “ester: ©” as used herein coldly refers to the esters of the compounds of the present invention that hydrolyze in the living body and include those that easily decompose in the human body Examples of non-toxic, pharmaceutically acceptable esters of the present invention include 0-6 alkyl esters, 0-6 alkyl esters and CoC cycloalkyl esters, although alkyl esters are preferred. Ci-Cq b©-,0.The esters of the compounds of formula (1) can be prepared according to the following methods:

ve traditional.

‎YAYA

The term denotes “pharmtically acceptable amide” or “amide 568; Also used in this statement are 5 non-toxic lg amides of the present invention derived from cammonia si sal alkyl compounds 0-0, primary © -C alkyl amines and dialkyl ©© amines secondary dialkyl amines and p - Secondary and in Als secondary amines the amine may also be in the form of a heterocyclic ring containing 6 Jo members and containing one nitrogen atom. Amides 5 derived from ammonia are preferred C-Cs, C=C, alkyl primary amides and C-Cs, dialkyl secondary amides Y©-0. The amides of compounds of formula (1) can be prepared according to conventional methods. Dosage forms for topical administration of the compounds Lady of the present invention include powders; and any preservatives; buffer solutions or propellants that may be required. This invention also includes ophthalmic formulations; ointments0 powders and ophthalmic solutions within its scope. The actual dosage levels of the active ingredientsve may change in Gag pharmacological compositions of this invention to obtain an amount of a compound or compounds of the present invention that is effective in obtaining the desired therapeutic response for a particular patient; certain formulations and method of administration. The dose level selected will depend on the effectiveness of the particular compound, the method of administration, the severity of the condition being treated and the condition of the patient However, it is a practice in the technique to start with doses of the compounds of the invention pl Mr at levels lower than those required to obtain the therapeutic effect cas eal and gradually increase the dose until the desired effect is obtained. The present invention includes the Gay compounds of the present invention either chemically synthesized or formed by administering an initial drug and then biotransformation later within the body al to obtain a compound according to the present invention. Yo and when used in the above and other processors; A therapeutically effective amount of the compounds of the present invention may be used in pure form or; Wherever such forms are found» in

VY.

A pharmaceutically acceptable salt or prodrug form. In the form eh, the compounds of the present invention may be given as a pharmaceutical composition containing a compound or compounds of the present invention in combination with one or more pharmaceutically acceptable excipients. The expression 'therapeutically effective amount' of a compound [Lig] of the invention means a sufficient amount of a compound or compounds of the present invention to treat sexual dysfunction; oo A reasonable benefit/risk ratio ALE for use in any medical treatment. However, he will understand that the total daily use of a compound or compounds of the present invention and their combinations will be determined by the supervising physician within the scope of proper medical judgment. The exact Ladle effective dose level for any given patient will depend on various factors including the sexual dysfunction treated and the severity of the sexual dysfunction; the potency of the compound or compounds of the present invention used; the particular installation used; 0 age bw; Public Health; the sex and diet of the patient; time of administration method of administration; the rate of excretion of a compound or compounds of the present invention; treatment duration; drugs used in combination or concomitantly with a compound or compounds of the present invention; Similar factors are well known in medical technologies. For example (Jha), it is very common in the technique to start with doses of a stimulant at levels lower than those needed to obtain the desired therapeutic effect.

1 and gradually increase the dose until the desired effect is obtained. The total daily dose of compounds of the present invention administered to humans or other animals may range from about 1.009 to about Vr mg/kg/day. for oral administration; More preferable doses may be in the range of about 0.00 to about 10 mg/kg/day. for sublingual administration; More preferable doses may be in the range of about (HY) about 15 mg/kg/day. If desired, the effective daily dose may be divided into multiple doses for administration; thus single dose formulations may contain these

The amounts or parts thereof to form the daily dose.

‎YAYA

Claims (1)

VY Protective Elements (1) Use of a compound of formula 1-1 A Re N N 3 CL TR ZN T Rc N Ro, IE (1) r Pharmaceutical form J 580 amide or amide ester salt Or salt ¢ used to treat sexual dysfunction medicament to make a medicine ° by giving the aforementioned dewy organism that is a mammal in a mammal sexual dysfunction 1 Cua therapeutically effective amount Ladle needed for this treatment an amount of 7 from the group which consists of BEC A 2 Ry Ra R R R Ry Ry Rz 1 fo 1 8 A | Tr » NN Ddan A Ar I L] 7 Anas ' ¢ A x 3 ' 0 0 < ASNT Re ' RY N Re ' Rg R2 R 1 Ra = R, Ry al Ra = X — ue NX ASS X Lx For Jar Ga 1 M L TY Mr VY WK 0 0 Ra A 3 Rg NT Rs + Rs Rin x N R R, Ra 4 X= 5 2 xX —N y / \ 1 b I N 5 i nb ab gla ' = 11 6 2 N ' x SN ' BS N 3 3 Rs ' Rs ' x L SA R « R > WNT EY of As MN . .N x I, oN N and AN ¢ x SN ¢ Rs | Lbr VY Cough 117 X A is chosen from the group consisting of NH 0 and 5; L 0 is chosen from the group consisting of CH,CH,CH, CH,CH, «CH, ¢CH,CH,CH,CH,; 3 ye Res Re (Rs Ry oR 3) each of them is selected separately from the group consisting of b alkoxy hydrogen alkenyl alkyl alkyl m sulfenyl calkylsulfinyl alkyl sulfur BERN calkylsulfonyl ferro alkylthio alkoxycarbonyl Jug S SS alkynyl alkyl carbonyl calkylcarbonyloxy carboxy cyano formyl chalogen (pa sla 2 haloalkoxy b< halogen » halo chaloalkyl J <hydroxy YY hydroxyalkyl ¢hydroxyalkyl marquette cmercapto nitro da Yr carbonyl (NZ Zy)earbonyl (NZ,Z,) and sulfonyl (NZ Zpsulfony !(NZ,Z,) where 7, re and 2 are chosen separately from the group consisting of the alkyl hydrogen Yeo, the calkylearbonyl, the alkylsulfonyl and the ¢formyl Rps Re Ry “Ry 5 are selected separately from the group consisting of chydrogen alkoxy alkoxy BEN alkenyl alkylsulfonyl Jui si pS BEES calkylsulfinyl YA alkyl in Mantabulla; alkylearbonyl alkylearbonyl calkylcarbonyloxy v. ccarboxy cyano formyl halogen 81 haloalkoxy haloalkoxy chaloalkyl hydroxy TY <700 hydroxy alkyl mercapto nitro 1772- and a carbonyl (NZ:Zy)carbony! (NZ,Z,) ry Re re is chosen from the group consisting of the alkoxycarbonyl hydrogen “alkoxycarbonyl ve alkyl calkyl carbonyl carylcarbonyl vi alkyl cyclocarbonyl als ” cycloalkylcarbonyl 4 heterocyclecarbonyl vv and a carbonyl ¢(NZ,Z;)carbonyl (NZ,Z,) RpYA chosen from the group consisting of a hydrogen and an alkyl erased YY ra 2 is chosen from the group consisting of C aN and 011; and ¢ bond --- present when 2 represents 2 carbon and not present when 2 represents 23.07 nitrogen (pas R .CH 1 7- use GE of claim 1 where Rps Re «Rp Ra Y each selected separately from the group consisting of 3 hydrogens and a thalogen (pa sla Jia Rg ¢ hydrogen thydrogen Z 5 representing a nitrogen atom tnitrogen 1 bond ~~ does not exist; and A v is R2 21 b Rs . Rs 9 where 1 for claimant Tay use -* 1 ¢CH, representing L 7 individually selected from the group consisting of Ros Re (Rs Ra 1 thalogen and two hydrogen halogens ¢ ¢hydrogen Rg ° thydrogen (ja represents hydro Re 1 'nitrogen Ja 27 4 Bond --- not present; A represents A 9 YAYA Vy R, : Ri Ra st Rs ; 'hydrogen, of which hydrogen JS represents Ras Rs «Ry 11, where 1 +; Re «Rp Ry thalogen and halogen hydrogen ¢ thydrogen hydrogen Jie Rg ° thydrogen represents hydrogen Re 3 tnitrogen a nitrogen atom (iar Z 7 bond --- not present; represents A a a Ra Ri A Ra Rs v 'hydrogen Each represents hydrogen Rss Ry each Ry 1 where 1 of claimant Gg use —o \ and each is selected separately from the group consisting of Re Rp «Ra 1 thalogen and halogen hydrogen 1 thydrogen represents hydrogen Rg ¢ 'nitrogen represents a non-existent 7° nitrogen atom; and m —bond 1 ha \Yo A v is Ra ,. 2 md Rq A Cus 1 Use of claim 1 -1 'CH, representing L Y and with each selected separately from the group consisting of Re Rp Ra 1 thalogen and two hydrogen halogens ¢ thydrogen represents hydrogen Rg 8 thydrogen represents hydrogen Re 7 tnitrogen represents nitrogen Z v bond ——— not present; A represents A 9 ra Ra ve m z = st Ras Ry Ry 1 each represents hydrogen 'hydrogen 1' 7- Use ly for claim 1 where LL 7 means 'CH, Re Rp Ry r' and so on. A unit of the group consisting of ¢ hydrogen and a halogen Rg ° represents a hydrogen thydrogen Re 1 represents an alkyl L Z represents a nitrogen atom ¢nitrogen A bond — -- not available; ‎YAYA A 9 represents a gt 2 | NT Ra 1 hydrogen lee represents each Ry Ry 11 1 8- Use Gg of claim 1 where 1 What Re «Rg and m are selected separately from the group consisting of hydrogen and ¢thalogen thydrogen is hydrogen Rg ¢ 2° represents a nitrogen atom 1 bond ——— does not exist; A 7 represents and Ri OY Rs gt x z NR A 9 B Rs Ry and B select each of them separately from the group consisting of 10 hydrogens and two hydroxy 1 5- Use lag for claim 1 where “Ra mal Ros Re are selected separately from the group consisting of 1 hydrogen and a halogen Rg § representing hydrogen thydrogen Re ° representing hydrogen thydrogen L 1 It represents “CH,” for 7 represents a nitrogen atom, tnitrogen ‎YAYA bond = not present; A is A a Ra (AN TRe b and thydrogen and ya each represents hydrogen Ry cry 1 'hydroxy b represents hydroxy VY where 1 is for the protective element Tay use 0 - 1 and each of them is selected on A unit of the group consisting of Re Ra (Ra thalogen) and a halogen hydrogen ¥ thydrogen represents hydrogen Rg £ ¢nitrogen represents a nitrogen atom Z ° --- bond not present; and 1 represents A v and Ra A d -11 1 the use Gy of claim 1 where Y A represents “CH, 1” and Re “Rg” Ra and what each is chosen separately from the group that It consists of ¢ hydrogen and a halogen Rg 2 representing hydrogen 1 b representing hydrogen thydrogen L Z representing a nitrogen atom ¢ nitrogen Mekha A bond --- does not exist; A 9 represents and NT Ra 1 d 5 Ris Ry (Ry 1 each represents hydrogen 'hydrogen -1 Y \ use la, of claim 1 where Rp 5 Re Ry Ra 1 is selected separately from the group consisting of v hydrogen and thalogen Jia Rg § hydrogen thydrogen o 7 represents a nitrogen atom tnitrogen 1 bond -- - does not exist; and A 7 is represented and R, A say N 7 -19 0 use according to claim 1 where 7 a represents CH, 1 and Re «Rp »Ra and M are each selected separately from the group which It consists of ¢ hydrogen and a halogen Rg ° representing hydrogen thydrogen Rp 1 representing hydro thydrogen (n> Z 7 representing a nitrogen atom tnitrogen A : bond == = not found; YAY A VTA Ja A 4 Ra xf 'Ny “Rj \ and thydrogen of which hydrogen is JS Ji and y Ry 1 sulfur represents a sulfur atom X VY where 1 of the protective element Gy Use SVE Each is selected Separately from the group consisting of Ros Re Rg Ry thalogen and halogen hydrogen Y calkoxycarbonyl is selected from the group consisting of alkoxyryotyl Rg ¢ Ji carylcarbonyl aryl carbonyl alkyl alkyl calkylcarbonyl carbonyl Ji 2 heterocyclecarbonyl heterocycle ccycloalkylearbonyl cycloalkylearbonyl cyclocarbonyl 1 ¢(NZ,Zy)carbonyl (NZ,Z5) and carbonyl 7' nitrogen Z A bond --- not present; and ; A ve Ro Rian Ra \ CAHOON TR Cus \ for the protection element lady to use | — Yo \ “CH, representing L Y and individually selected from the group consisting of Re «Rg »Ra v ¢halogen and the t calkoxycarbonyl halogen hydrogen from the group consisting of alkoxycrylotyl URI Rg > non-(NZ,Z;)carbonyl (N2,2,) carbonyl ring alkylcarbonyl 1 YAYA Vr, where the part of the heterocycle is the heterocyclecarbonyl of the aforementioned heterocyclecarbonyl in the group of the heterocyclic carbonyl heterocycle A ¢pyrrolidinyl is pyrrolidinyl q thydrogen represents hydrogen Re ve tnitrogen represents a nitrogen atom 2 1 Association --- does not exist; VY represents A VY Ra i | Mm 0 hydrogen each represents hydrogen Ris Rs “Ry Ve where 1 is the use according to claim 11-1 and each of them is not selected separately from the group consisting of Re “Rg” Ra Y thalogen and halogen Y hydrogen Jie Re ¢ 'CH representing Z 0 bond -<-- does not exist; And 1 represents A v Ro Riv Ra xx 8 A. Rs where 1 use pursuant to claim 17 1 'CH, A' represents each selected separately from the group consisting of Ros Re Rp (Ra v Maha 1 thalogen (p> sia and hydrogen ¢ thydrogen hydrogen Jie Re ° thydrogen represents hydrogen + 3 'CH represents 7 7 The bond sana does not exist; A Jas A 4 Ra R; PL ya - y bar 1 st Rs 'hydrogen of which hydrogen is JS and ba represents 1 Ry Ry where 1 Alaa) of an element (ad al use = YA \ each of which is selected separately from the group that It consists of Rp s Re «Rp »Ra Y thalogen and a hydrogen halogen 7 thydrogen Jae O ¢ “CH represents Z 0 bond that does not exist; and 3 Jha A L and Rye Ra A Ker Ba TR where 1 M according to claim Ana -08 1 'CH, L Y represents each of them separately from the group consisting of Ja) Rp Re « Rp «Ra v thalogen and halogen hydrogen ¢ YAYA VEY thydrogen Je "Rg ° thydrogen hydrogen Sra Re 1 'CH Z for bond ——— does not exist; A stands for A 9 Ra 1 gt 5 km z Ra hydrogen is a hydrogen and a lee which represents each Ry Ry 11 wherein 1 is the use pursuant to claim 0 - 1 and each is not separately selected from the group consisting of Re «Rs Ra thalogen and hydrogen halogen Hydrogen 1 thydrogen hydrogen Ju mi ¢ tcarbon represents carbon atom Z 2 bond ——— present; 1 represents A v Ra R; 6 butt - Ra . Rs A where 1 Use in accordance with Claim 71-1 “CH, NL L Y each to be selected separately from the group consisting of Rps Re Re Ra r ¢halogen, hydrogen halogen and £ thydrogen Je Rg ° mh Dhydrogen Jie hydrogen + 1 A Z represents a ¢carbon atom A bond --- exists; A 9 represents Ra 8 Free God Rs Rs 1 f hydrogen and each represents hydrogen Rs Ry 1 1-1 use aig of claim 1 where the compound mentioned in formula (1) of Y is chosen from the group consisting of: M "-[(©-phenyl-» (HY) 1-linideriborde GALE methyl]-111-benzoimidazole ¢2-[(4-phenyl-3,6-dihydropyridin-1(2H)-yl)methyl [-1 H-benzimidazoie ¢ > 77[(-phenylpiperazin-1-yljmethyl}-1 H-benzimidazole 1 ¢2-[(4-phenylpiperazin-1-yljmethyl))-111-benzimidazole SHY)EY v imidazolyl (1(methyl)piperazinyl](1)benzonitrile ¢2-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1-yljbenzon itrile A Js aad methyl)-111-ben [(V)chlorophenyl)piperazinyl-7(- 41-7" 9 ¢2-{[4~(2-chlorophenyl)piperazin-1-ylJmethyl}-1 H -benzimidazole ye piperazinil ))([methyl)-111-benzimidazole (Js 5 ¥) =] 0 ¢2-{[4-(2-fluorophenyl)piperazin-1-yl}methyl}-1 H-benzimidazole \Y-methyl)-111-benzimidazole](1) piperazinyl (Js oti Y) = 4-7 Vr ¢2-{[4-(2-nitrophenyl)piperazin-1-y1jmethyl}-1 H-benzimidazole Ve methyl)-111-benzimidazole [(V)-(7-methoxyphenyl)piperazinyl [1-7 ve ¢2-{[4-(2-methoxyphenyl)piperazin-1-yl)methyl}- 1H-benzimidazole 3 2-methyl)-111-benzimidazole (1)-(71-40-(methylthio)phenyl]piperazinyl VY ‎YAYA ({4-[2-(methylthio)phenyl]piperazin- 1-yl)methyl)-1H-benzimidazole YA EY 1-(7-echoxyphenyl)piperazinyl])1(methyl)-111-benzoimidazole £2-{ [4-(2-ethoxyphenyl)piperazin- 1-yljmethyl}-1 H-benzimidazole Y- Lonf](1) benzimidazolyl (7(methyl)piperazinil 1)-0-7 Ty £2-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1 -vljphenol YY Lonf](1(methyl)piperazin) (Y)-(111-benzoimidazolyl 41-4 TY [1)-4]-4; H-benzimidazol-2-ylmethyl)piperazin-1 -yl] phenol Ye ve 1-1 -(7-methyl_pyridinyl (?)) piperazinyl iH) {die ])1(-methylpyridin-2-yl)piperazin-1 -yl]methyl}-1 H-benzimidazole 3 4-3[{-2 1 (- - Tv benzimidazolyl (Y)methyl)piperazinyl])1(nicotinotrile H-benzimidazol-2-ylmethyl)piperazin-1 -yl]nicotinotrile YA 1 (-4[-$2 SUEY 0 ve bromo-7-[(-pyridinyl (7) piperazinyl mb) [ie ))1(imidazole 7-dibromo-2-[(4-pyridin-2-y1 piperazin-1-yl) methyl}-1 H-benzimidazole Tv ¢5 Ty 0-fluoro-1-7(-pyridinyl(7)piperazinyl((V)methyl]-1171-benz-imbidazole ¢5-fluoro-2-[(4-pyridin-2-ylpiperzin-1) -yl)methyl}-1H-benzimidazole TY Jie) 4-7 rY pyridinyl (((Y) piperazinyl [(V)methyl)-111-benzimidazole [4-(6-methylpyridin-2- yl)piperazin-1-ylJmethyl}-1H-benzimidazole vi{-£2 (7) pyridinyl])1(methyl)piperazinyl (Y)-(111-benzimidazolyl[1-7(4ro N-{2-[4-(1H-benzimidazo1-2-) ylmethyl)piperazin-1-yl} pyridin-3-yl} methanesulfonamide 4 ¢methanesulfonamide TV methyl)-111-benzimidazole [(1) piperazinyl ((Y)-(7-fluoropyridinyl) 41 -7 TA $2-{[4-(3 ~fluoropyridin-2-yl)piperazin-1 -ylJmethyl}-1H-benzimidazole v4 benzimidazole HY methyl]-)1( J) (7)" -[(; (“-methyl-; ‎YAYA 0 tt "-(57(1)-7-methyl--pyridinyl(7)piperazinyl])1(mgel)-111-benzimidazole ¢2-{[(2S)-2-methyl-4- pyrid in-2-ylpiperazin-1-ylJmethyl}-1 H-benzimidazole £0 die TRY) 1 = $-piperidinyl(7)piperazinyl])1(methyl)-111-benzimidazole [(2R) -2-methyl-4-pyridin-2-ylpiperazin-1 -ylJmethyl}-1H-benzimidazole 7 {-¢2 (©) pyridinol](1) benzimidazolyl (7(methyl)piperazinyl) HY (-41-7£A¢6-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1 -yl} pyridin-3-ol £4 dim (1-7 2(?)piperazinyl))1(methyl]-111-benzimidazole ¢2-[(4-pyrimidin-2-ylpiperazin-1-yl)methyl]-1 H-benzimidazole 01 2 41-7("-thiazolyl (1) piperazinyl])1(myst)-111-benzimidazole ¢2-{[4-(1,3-thiazol-2-yl)piperazin-1-yl [methyl}-1 H-benzimidazole oY of 1-7(-pyridinyl (?) piperazinyl)1(methyl]-111-benzimidazole-1-carboxylate co-isobutyl 2-[ (4-pyridin-2-ylpiperazin-1-yl)methyl]- 1H-benzimidazole-1- 'carboxylate 25' ov “-1(;-pyridinyl(Y)piperazinyl(1)linadilorib(-1-]lithem))1(carbonyl)-11-oA benzimidazole 2-[(4-pyridin) -2-ylpiperazin-1-y1 Ymethyl]-1-(pyrrolidin-l-ylcarbonyl)- ¢1H-benzimidazole 4 1 dimethyl (Y= 17€)-pyridinyl(7)piperazinyl (1)methyl]-111-benzimidazole-1)1-carbohydrate N,N-dimethyl-2-[(4-pyridin) -2-ylpiperazin-1-yl)methyl]-1H- ¢tbenzimidazole-1-carboxamide +7 2 di((1)tartrate)IY-pyridinyl (7(piperazinyl)(1(methyl)] - [1 1¢ benzimidazole 2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1H-benzimidazole ¢bis((L)tartrate) 10 " "-(1? -(7-methoxy])1( desis pa (J methyl)-117-benzimidazole ¢2-{[4-(2-methoxyphenyl)piperidin-1-y1]methyl}-1 H-benzimidazole Tv and A 1-7(-pyridinyl (Y) piperidinyl) 1(methyl]-111-benzimidazole 2-[(4-pyridin-2-ylpiperadin-l-y)methyl]-1H-benzimidazole 19 or pharmaceutically acceptable salt ‎YAYA Mr. Dr For a pharmaceutically acceptable salt of it. 01 77- Use of claim 1 by Gg of a compound of formula (1) or a salt thereof; a pharmaceutically acceptable amide Y ester thereof in combination with a phosphodiesterase inhibitor © 5 phosphodiesterase A inhibitor ¥ His choice of sildenafil and vardenafil to make a medicament ¢ is used to treat sexual dysfunction in a mammal ° organism by giving the aforementioned gynecomastia an amount of therapeutically effective Ladle Yad -amount hl 1 - Use lad N of protectant 1 of a compound of formula 0 or a pharmaceutically acceptable Y06 ¢salt or ester or amide thereof in combination with an adrenergic receptor antagonist 1 Then it is selected from terazosin 0, prazosin ¢ and tamsulosin 0, to make a medicine that is used to treat sexual dysfunction in the Dubai mammal organism by giving the aforementioned dewy organism 1 effective amount Ladle. \ - Use according to claim 1 of a compound of formula (1) or a pharmaceutically acceptable salt ester or amide v thereof in combination with a dopamine agonist of 7 apomorphine to make A medicament used to treat sexual dysfunction in (AS) mammal breasts by giving the aforementioned oa AY ° a therapeutically effective amount YY \ = use according to either Claim TE YY or 75 where the compound of formula (1) is chosen from the group consisting of 1 1-7 -(7-methylpyridinyl (((Y)piperazinyl]) 1(methyl)-141-benzimidazole ¢2-{[4-(3-methylpyridin-2-yl)piperazin-1-y [Jmethyl}-1H-benzimidazole ¢ No SHY) 41-7 imidazolyl (7(methyl)piperazinyl](1)nicotinotrile ¢2-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1-yl] 1 nicotinonitrile v©« la-dibromo-7-[(?-pyridinyl(7)piperazinyl))1(methyl]-111-benzimidazole 7-dibromo-2-[(4-pyridin-2-ylpiperazin) -l-yl)methyl}- 1H-benzimidazole A,5? 9 50-Fluoro-7-[(?-pyridinyl((1)(piperazinyl))1(mgyl]-171-benzimidazole ¢5-fluoro-2-[(4-pyridin-2-ylpiperazin) -1-yl)methyl]-1H-benzimidazole yo (((Y) Jail ™ OQ) [1-7" 1-piperazinyl])1(methyl)-111-benzimidazole ¢2-{[4-(1,3-thiazol-2-yl)piperazin -l-y{]methyl}- 1H-benzimidazole VY ir (6-pyridinyl (1) piperazinyl) (1)methyl]-111-benzimidazole-1-carboxylate "isobutyl 2-[(4) -pyridin-2-ylpiperazin-1-yl)methyl]-1H-benzimidazole-1- yo atmani «and feed? (DS (1) linidlorib(-1-]lithem(0)”-1();-pyridyl (¥) piperazetyl) 1 2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]- 1-(pyrrolidin-1-ylcarbonyl)-N-benzimidazole ¢1H-benzimidazole VA 4-mde 1-7(-pyridinyl(7) piperazinyl “HY [dia 1)(7-benzimidazole-1-carboketsamide N N-dimethyl-2-[(4-pyridin-2-y) 1 piperazin-1- ¢yl)methyl]-1H-benzimidazole-1-carboxamide 1 YY “-[(4-phenylpiperazinyl) (1(myl)]-11-benzimidazole ¢2- [(4-phenylpiperazin-1-yl)methyl]-1H-benzimidazole YY rt 177 (11-benzimidazolyl)1(methyl)piperazinyl(1)]-benzonitrile ¢2-[4-(1H-) benzimidazol-2-ylmethyl)piperazin-l-yl}benzonitrile Yo 1 41-7 -(7-chlorophenyl)piperazetyl [(V)methyl)-11-benzoimidazole ¢2-{[4-(2-) chlorophenyl)piperazin-1-ylJmethyl}-1H-benzimidazole 77 YA 41-7 -(7-fluorophyll)piperazinyl])1(methyl)-111-benzimidazole ¢2-{[4-(2) -fluorophenyl)piperazin-1-ylJmethyl}-1H-benzimidazole YA £11 -(7-nitrophenyl)piperazinyl])1(methyl)-111-benzimidazole 1H ¢2-{[4-(2-nitrophenyl)piperazin-l-ylJmethyl}-1 H-benzimidazole 7911 mY 7-([;-(7-methetoxyphenyl)piperazinyl])1(methyl) -111-benzimidazole ¢2-{[4-(2-methoxyphenyl)piperazin-1 -yl]methyl}-1H-benzimidazole TY HY) = EE re benzimidazolyl (1(methyl)piperazinyl) 1)]phenol [¢4-[4-(1H-benzimidazol-2-y Imethyl)piperazin-1 -yl]phenol vo dir T1 8)a 55(phenyl]piperazinyl (1(methyl)-111) -benzimidazole ¢2-({4-[2-methylthio)phenyl]piperazin-1-yl} methyl)-1 H-benzimidazole vv TA 2-7 -(7-ethoxyphenyl)piperazinyl])1 ( Mgyl)-111-benzimidazole ¢2-{[4-(2-ethoxyphenyl)piperazin-1-yljmethyl}-1 H-benzimidazole Ya 2 41-7 -(111-benzimidazolyl)¥(methyl)piperazinyl (1)]Phenol ¢2-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1-yl]phenol 3 JY 5-(7-methoxyphenyl)piperidinyl](1)methyl )-1-O-benz imidazole L and neglected because 11-6 1-(1-lgtd[a-1-absorbed um(1 pg nam buh 21 2-00)-2-1[4? tt]”-] ; "-[(; -vinyl-; (HY) 1-Linihydropyridine (SUE methyl]-111-benzimidazole ¢2-[(4-phenyl-3,6-dihydropyridin-1(2H)-yl)methyl]-1 H-benzimidazolc 7 tA 1-7-(7-methylpyridinyl ))1(piperazinyl])1(methyl)-111-benzimidazole ¢2-{[4-(6-methylpyridin-2-yl)piperazin- ylJmethyl}-1H-benzimidazole £9 0 +-1(*methyl-”-pyridinyl (1) dom (0) methyl]- 111 3a amidazole ¢2-[(2-methyl-4-) pyridin-2-ylpiperazin-1-yhmethyl]-1 H-benzimidazole 51 2 11-7( 57)-7-methyl-?-pyridinyl (1) piperazinyl [(1-methyl)-111-benz imidazole ¢2-{[(2S)-2-methyl-4-pyridin-2-ylpiperazin-1-yljmethyl}-1 H-benzimidazole ey ot 10-7(87)-7-methyl-?- Pyridinyl(Y)piperazinyl])1(methyl)-111-benzimidazole ¢2-{[(2R)-2-methyl-4-pyridin-2-ylpiperazin-1-ylJmethyl}-1H-benzim isole co 21-(7-[4-(111-benz imidase) lyl(Y)methyl)piperazetinyl](1)pyridinyl (7) YAYA ev methanesulfonamide N-{2-(4-(1H-benzimidazol-2-ylmethyl)piperazin-1-yl]pyridin-3- ¢yl}methanesulfonamide eA 2" 17-(7-fluoropyridinyl ( 7)) piperazinil sir HY {dia ](1)imidazole ¢2-{[4-(3-fluoropyridin-2-yl)piperazin-1-yljmethyl}-1 H-benzimidazole Te (Y) dn 1 1 piperazinil (1)methyl]-ar zyme dazole ¢2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1H-benzimidazole TY it 7 )1 (Tartrate) 1-Pyridinyl (¥) piperazinil (1) methyl]-1 11-benzoimidazole generic Am-111-[Abta-Zap 1 Amt-1 and 2-MnC-4)]-2 tbis((L) (tartrate) te 1 7[-pyrimidinyl (1) piperazinyl (1)methyl]-111-benzimidazole ¢2-[(4-pyrimidin-2-ylpiperazin-1-yl)methyl]- 1H-benzimidazole Tv and A 111-17-1 benzimidazolyl (1(methyl)piperazine](1)pyridinol (©) 6-[4-(1H-benzimidazol-2-ylmethyl)piperazin -l-yl]pyridin-3-ol 14 or a pharmaceutically acceptable salt thereof. Y of it to make a medicine Medicament used to treat erectile dysfunction Y Dysfunction in a male human by giving the aforementioned male who needs this treatment a therapeutically effective amount Ladle 1 1 Use according to claim TV, where the compound mentioned in formula (1) is chosen from the group consisting of 1 1-7 (7-methylpyridinyl ((Y)piperazinyl])1(methylated)-111-benzimidazole ¢2-{[4-(3-methylpyridin-2-yl)piperazin-1-ylJmethyl}-1H-benzimidazole 1 77-(111-benzimidazolyl)1(methyl)piperazinyl](1)nicotonitrile ¢2-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1-yl]nicotinotrile 1 l © ses 0 (SY 7-[(? -pyridinyl (1)piperazinyl (1)methyl]-111-benzimidazole 10 t VE¢5_7-dibromo-2-[(4-pyrid in-2-ylpiperazin-I-yl)methy!]-1H-benzimidazole A 117-benzimidazole [0a ))1( piperazinyl (Y) - Pyridinyl ?([-7-rolf-0 : ¢5-fluoro-2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]- 1H-benzimidazole 0.1methyl)-111-benz Imidazole](1) piperazinyl ((Y) 7-thiazolyl (1-7 VY ¢2-([4-(1,3-thiazol-2-yl)piperazin-1-ylJmethyl}-1 H y-benzimidazole y telescope-1-lozademia methyl]-111-benz (1) “-[();-pyridinyl (7) piperazinyl VY isobutyl 2-[(4-pyridin-2-ylpiperazin-1-yl) (methy!]-H-benzimidazole-I-isobutyl Vi ¢carboxylate Veo carbonyl (11-(1) linadilorib)-1-[lethem (1)-pyridinyl (7) piperazinyl (1) -7 Vy 2-[(4-pyridin-2-ylpiperazin-l-yl)methyl-1-(pyrrolidin- 1-ylcarbonyl)-1H- p-benz imidazole ?602111102206 VA methyl]-11- (1) piperazinil (VF) dimethyl-ta); 7 ¢yl)methyl]-1H-benzimidazole-1-carboxamide 7 mehl]-111-benimidazole (1)-phylylpiperazine EY YY 2-[(4-phenylpiperazin-1-y!)methyl] -1H-benzimidazole YY benzonitrile](1(imidazolyl)¥(methyl)piperazinyl sr HY) = EY ve ¢2-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1-yl]benzonitrile Ye methyl)-111-benzimidazole](1)-(7-chlorophenyl)piperazine EY 7 ¢2-{[4-(2-chlorophenyl)piperazin-l-ylJmethyl}-1 H-benzimidazole Tv methyl (-111-benzimidazole](1)fluorophenyl)piperazinyl-7(- 21-7 YA ¢2-{[4-(2-fluorophenyl)piperazin-1-yljmethyl}-1 H-benzimidazole 5 methyl )- 111-benzimidazole [(1)-(7-nitrophenyl) piperazinil 41-7 r. ¢2-{[4-(2-nitrophenyl)piperazin-l-ylmethyl}-1 H-benzimidazole 91-methyl)-111-benzimidazole](1)-(7-methoxyphenyl)piperazinyl 41-7 ry ¢2-{[4-(2-methoxyphenyl)piperazin-1-yl]methyl}-1 H-benzimidazole YY 061 FQOL](1(methyl)piperazinyl) (1)-(111-benzimidazolyl) 4-4 Tt ¢4-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1-yl]phenol ve Js aed methyl)-111-benz (1)-71-(methylthio)phenyl]piperazinyl (77 8 ¢2-({4-[2-(methylthio)phenyl]piperazin-l-yl } methyl)-1 H-benzimidazole vv methyl)-111 benzimidazole](1)-(7-ethoxyphenyl)piperazin 1-7 i ¢2-{[4-(2-ethoxyphenyl)piperazin-1- yljmethyl}- 1H-benzimidazole v4 lvv](1) methyl)piperazinyl(1)-benzimidazole 111(- 41-7 2¢2-[4-(1H-benzimidazol-2-yImethyl)piperazin-1 -yljphenol 3-methyl)-111-benzimidazole](1) -(7-methoxyphenyl)piperidinyl [1-7 ey £2-{[4-(2-methoxyphenyl)piperidin-1-ylmethyl}- 1H-benzimidazole ey imidazole ir HY [df (1))((pyridinyl (7) piperidinyl) (1-7 3 ¢2-[(4-pyridin-2-ylpiperidin-1-yl)methyl]-1H- benzimidazole go imidazole znb-111-[lithium (HY) 1-linideripurhyd (SUE 7-[(?-phenyl-”-3¢2-[(4-phenyl-3,6-dihydropyridin) -1(2H)-yl)methyl]-1 H-benzimidazole gv methyl)-11-benzimidazole](1)piperazinyl ((Y)-(-methylpyridinyl) 41-7£A¢2- {[4-(6-methylpyridin-2-yl)piperazin-1-ylJmethyl}-1H-benzimidazole £4 methyl]-111-benzyimidazole (1) piperazinyl (1)"-[(7) -methyl-4-pyridinyl 8¢2-[(2-methyl-4-pyridin-2-ylpiperazin-1-yl)methyl]-1H-benzimidazole 1H-methyl)-111-benzimidazole](1) Piperazinil (1( 57)-7-methyl-? -pyridinyl (1-7 oY¢2-{[(2S)-2-methyl-4-pyridin-2-ylpiperazin-1-yl]methyl} - 1 H-benzimidazole ov methyl)-111-benzoimidazole [(V) piperazinil (Y) ?8)-7-methyl-? - Pyridinyl (1-7 8 abjata ah (An-a-mt 1m l-2-r ra-4- patta 2-1102-(2-1])28? (1-H-benzimidazole oo))© ( pyridinyl ])1(methyl)piperazinyl) 1(imidazolyl SHY ) =] YN > N-{2-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1-yl]pyridin- 3-methane sulfonamide ov ¢yl } methanesulfonamide oA methyl)-111-benzimidazole [(1)piperazinyl](1) 11-7;-(7-fluoropyridinyl 29 YAYA VEY ¢2-{[4-(3-fluoropyridin-2-yl)piperazin-1-yl]methy!} -1H-benzimidazole 1.2"-[(;-pyridinyl(Y)piperazinyl) (1) methyl]-111-benzimidazole [¢2-[(4-pyridin-2-ylpiperazin-1-yhmethyl]- 1H-benzimidazole TY 17 di(1) tartrate) ?-[(;-pyridinyl) ¥( piperazinil “die ))1( 11 11 benzimidazole 2-[(4-pyridin-2-ylpiperazin-l-yl)methyl]-1H-benzimidazole ‎¢bis((L)tartrate) Ne 1-7(-pyrimidin(Y)piperazinyl)1(methyl]-111-benzimidazole ¢2-[(4-pyrimidin-2-ylpiperazin-1-yl)methyl]-1H-benzimidazole Tv and A 3[€-(111-benzimidazolyl)1(methyl)piperazinyl(1)]pyridinol (7(6-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1 -yl]pyridin-3-ol 19 or a pharmaceutically acceptable salt From it to make a 21D medicine that is used to treat sexual dysfunction Y in a female human by giving the aforementioned human female 1 who needs this treatment a therapeutic amount of Ylad therapeutically. .effective amount ° 0 \ use according to claim 74 where the compound mentioned in formula (1) is chosen from the Y group consisting of v41-7-(7-methylpyridinyl((Y)piperazinyl) [(V)methyl)-111-benzimidazole ¢2-{[4-(3-methylpyridin-2-yl)piperazin-1-yl]methyl}- 1 H-benzimidazole ¢ : 41-7 - (111-benzimidazolyl (7(methyl)piperazinyl])1(nicotinotrile) ¢2-[4-(1H-benzimidazol-2-ylmethyl)piperazin-l-yl]nicotinonitrile 1 00 1-dibromo- 7-[(;-pyridinyl(Y)piperazinyl))1(methyl]-111-benzimidazole 7-dibromo-2-[(4-pyridin-2-ylpiperazin-1-yl)methyl] - 1 H-benzimidazole A, £5,000 Ver ©-fluoro-7-[(?-pyridinyl(1)(piperazinyl))1(methyl]-111-benzimidazole ¢S-fluoro-2-[(4-pyridin-2-ylpiperazin-1) -yl)methyl]-1H-benzimidazole 1 01 1-7( 7-thiazolyl ))1(piperazinyl])1(methyl)-11-benzimidazole ¢2-{[4-( 1,3-thiazol-2-yl)piperazin-1-ylJmethyl}-1H-benzimidazole 1" Tr "-[(;-pyridinyl(1)piperazinyl SoH [da))1(imidazole-) 1-Vi-isobutyl carboxylate 2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1H-benzimidazole-1- ¢tcarboxylate yo 0 17)-pyridinyl (1) piperazinyl “H(t (0) linidilorib(-1-]lithium))1(benzimidazole 2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1-(pyrrolidin-l-y lcarbonyl) - ¢]1H-benzimidazole VA SL ENN vo methyl-1-7[-pyridinyl(7) piperazinyl SH Tie ))1(1-benzimidazole-1-carboxamide N,N -dimethyl-2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]- ¢1H-benzimidazole-1-carboxamide 71 Jif)YY piperazinyl dsm dH [fe ))1( ¢2-[(4-phenylpiperazin-l-yl)methyl]-1H-benzimidazole YY vt 7-[4-(111-benzimidazolyl)1(methyl)(1)piperazinyl]-butzonitrile ¢2-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1-yl]benzonitrile Ye TY 7-([4-(7-chlorophenyl)piperazine [(V)methyl)-111 -benzimidazole ¢2-{[4-(2-chlorophenyl)piperazin-l-yljmethy!}-1H-benzimidazole TY YA "-([4-(7-fluorophenyl)piperazinyl](1) methyl)-111-benzoimidazole i ¢2-{[4-(2-fluorophenyl)piperazin-1-yl methyl} -1H-benzimidazole 7 4-7-(7-nitrophenyl)piperazinyl 3am HY {a ] (1) imidazole ¢2-{[4-(2-nitrophenyl)piperazin-1-ylJmethyl}-1II-benzimidazole 1 ry 7-([4;-(7-methoxyphenyl)piperazinyl]) 1(methyl)-111-benzimidazole ¢2-{[4-(2-methoxyphenyl)piperazin-1-ylJmethyl}-1H-benzimidazole Yr re 41-4 -(111-benzimidazole (VY) ) methyl) piperazinil (1)]phenol erased Vee «4-4-1 H-benzimidazol-2-ylmethyl(piperazin-1-yl]phenol ve methyl)-111-benzimidazole (1)(methylthio)phenyl[7-piperazin]-( 77 8 ¢ 2-({4-[2-(methylthio)phenyl]piperazin-1-yl} methyl)-1H-benzimidazole vv methyl)-111-benzoimidazole])1(phenyl)piperazin a SY ) 477 vA ¢2-{[4-(2-ethoxyphenyl)piperazin-1 -yl]methyl}-1H-benzimidazole v4 lonf](1)piperazinyl (die(7)benzimidazolyl 111)-7" 5 ¢2-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1 -yl]phenol 3 imidazole sir HY {die](1) piperidinyl (Jit nS fe Y= 4-7 3 ¢2 -{[4-(2-methoxyphenyl)piperidin-1 -ylJmethyl}-1H-benzimidazole LY imbdazole im HY [die ((V) piperidinyl (Y) 7-[();-(pyridinyl 0 ¢) 2-[(4-pyridin-2-ylpiperidin-1-yl)methyl]-1 H-benzimidazole to methyl]-111-benzimidazole (HY) 1-linideriborde SUT . 7-[(;-phenyl) £1 ¢-[(4-phenyl-3,6-dihydropyridin-1 (2H)-yl)methyl]-1H-benzimidazole Lv-methyl)-111-benzimidazole [(1)piperazole) (Y) -(-methylpyridinyl EDT 7 ¢2-{[4-(6-methylpyridin-2-yl)piperazin-1-yl] methyl} -1H-benzimidazole £9 methyl]-111-benzimidazole ) (1) Piperazinil (Y) ?-methyl-? -pyridinyl (1-7 9 ¢ 2-[(2-methyl-4-pyridin-2-ylpiperazin-1-yl)methyl}- 1H-benzimidazole eo Js aad sar HY {die ](1) piperazinil ( Y) 7-(57(1)-7-methyl-?-pyridinyl 2 ¢ 2-{[(2S)-2-methyl-4-pyridin-2-ylpiperazin-1 -yl]methyl}-1H- benzimidazole ey methyl)-111-benzimidazole [(1) piperazinil (Y) 87(1177)-7-methyl-?<pyridinyl oe¢2-{[(2R)-2-methyl-4- pyridin-2-ylpiperazin-1 -yllmethyl}-1H-benzimidazole ce))©0( pyridinyl])1(methyl)piperazinyl (Y) imidazole Sum HY = 41-71 8 N-{2- [4-(1H-benzimidazol-2-ylmethyl)piperazin-1-yl}pyridin-3-yl}methanesulfonamide of ¢methanesulfonamide oA-methyl)-111-benzimidazole])1((?)) piperazinyl dims ps) = 77 4 ¢ 2-{[4-(3-fluoropyridin-2-yl)piperazin-1 -yljmethyl}-1H-benzimidazole 1 mkah Vee nN -g[ ;? Pyridinyl(1)piperazin-1(methyl]-111-benzimidazole ¢2-[(4-pyridin-2-ylpiperazin-1 -yDmethyl]-1H-benzimidazole 27 1 di(1) tartrate) OY-pyridinyl (1) piperazinyl (1)methyl]-111 nt-benzimidazole 2-[(4-pyridin-2-ylpiperazin-1-) yl)methyl]-1H-benzimidazole ¢bis((L)tartrate) Te Odsal methyl]-laban (1) piperazinyl (7) dpm ert) 1 and ¢2-[(4-pyrimidin-2-ylpiperazin-l-yl)methyl]-1H-benzimidazole TY (7) Pyridinol])1(methyl)piperazinyl (Y)-(111-benzimidazolyl-41-1A) or pharmaceutically acceptable salt 6-[4-(1-H-benzimidazol-2-) y Imethyl)piperazin-1-yl}pyridin-3-ol 19 of it. Pharmaceutically acceptable salt x (1) is a compound of the formula =F A Ra 2 1 search NX Re 8 for Ro Re (11) v where odie Wana is acceptable amide or amide ester csalt or salt ¢ is chosen from The group consisting of A ° Ry, Ra Ri Ry 1 - R, Ra Ry ve Sob is J, re Rs Rs Wy” Rs “6 AN m35 YAYA Ven Ra rr hal rs Wh m 7 ah a b y Rs . Rs + m5 yber Ry R x XN A re Ma ll "Rbd Lamikil Makhabad Re Rs A rd Lo Jo Tok ¢ and ' 5 (S50 NH is selected from the group consisting of X 0 CH,CH,CH, «CH,CH, «CH, to be selected from the group consisting of 1 1 and a mqtet bit; VY Ry Ry Ry Ry \Y and each selected separately from the group consisting of ¢ \ hydrogen Calkenyl BEES «alkoxy SS hydrogen Alkyl J <i calkyl Vo sulfenyl J calkylsulfinyl sulfonyl Jy calkylsulfonyl VY calkylthio 3 alkoxycarbonyl alkyl carbonyl calkylearbonyl VY calkylearbonyloxy carboxy coyano formyl YA halogen <halogen haloalkyl J < i lla < haloalkoxy 01 hydroxyalkyl hydroxyalkyl mercapto ¢mercapto nitro 812,22 and carbonyl (NZ,Z5) residuals (012,2); Where , 7,57 is selected separately 28 from the group consisting of chydrogen calkyl alkyl carbonyl YY alkyl sulfonyl and formyl ¢formyl Ros Re (Rp Ra Yr) each is selected of which separately from the group consisting of Yt chydrogen calkoxy alkenyl calkenyl alkyl alkyl Yo sulfenyl calkylsulfiny! calkynyl calkoxycarbonyl alkyl carbonyl calkylcarbonyl J carbonylcarbonyloxy carboxyroto cyano “cyano formyl Vey chaloalkyl J gla chaloalkoxy chalogen halogen “formyl YA cnitro nitro cmercapto s2S je hydroxyalkyl hydroxy alkyl chydroxy 75 M7 and carbonyl (:212,2) al-Astamida (017,2; r. The alkoxy hydrogen is chosen from the group consisting of hydrogen Re ry aryl carbonyl calkylearbonyl alkyl carbonyl alkyl alkyl calkoxycarbonyl YY heterocyclic ccycloalkylcarbonyl alkyl cyclocarbonyl carylcarbonyl vy and ¢ (NZ,Z;)carbonyl (NZ,2,) and a heterocyclecarbonyl carbonyl ve talkyl carbonyl and an alkyl hydrogen is chosen from the group consisting of hydrogens Re re A provided that when it represents 4 and JS 1 Xs SN represents an esulfur atom, so Ry or Ry represents Ac gana other than ra hydrogen 'hydrogen TY compound according to claim 1 where Re «Rp »Ry 7 And with each of them chosen separately from the group consisting of 7 hydrogens and halogens (60 p1810; m Jet is hydrogen thydrogen and A ° represents And Rs s Jr, | : —VY 1 compound according to claim 1? where Re «Rp »Ry Y and what are selected separately from the group consisting of ¥ hydrogen and thalogen ‏ ‎YAYA VEA hydrogen hydrogen Jel Re ¢ hydrogen hydrogen Ja m ° (CH, represents L 1 represents A L acid R Yn 5 a O 'hydrogen O' Each represents a hydrogen Ry «Ry 9 where it is 0 il esl for Lady's waist compound 1-methyl]-111-benzimidazole (1) piperazinyl (VY)-pyrimidyl ( 1-7 Y .2-[(4-pyrimidin-2-ylpiperazin-1-yl)methyl]-1 H-benzimidazole 3 (I) 8?- compound with formula 1 R 2 M 8 A B M A Ra Y : 0 8 <7 ا> N NN DES Re ON Rp TE (111) 3 Pharmacologically acceptable of it, where amide or amide ester yd csalt or salt ¢ and each of them is chosen according to A unit of the group consisting of R; Ry; VATA yea CH,CH,CH, «CH,CH, «CH; Choose from the group consisting of L 9 ¢CH,CH,CH,CH, 3 01 Ros Re Rp Ra 1 are each selected separately from the group consisting of VY chydrogen alkoxy alkenyl alkyl alkyl VY capronyl calkylsulfinyl alkyl sulfite J < I catkylsulfonyl Ve alkylthio Ve calkynyl alkoxycarbony <alkoxycarbony! chaloalogen chaloalkoxy halo haloalkyl J <li VY hydroxy hydroxyalkyl mercapto -NZ\Z, nitro VA and carbonyl Cus (NZ Z)) carbonyl (NZ,2y) 7,57 JS separately selected 1 from the group consisting of alkyl chydrogen catkyl alkyl carbonyl 1 alkyl sulfonyl and 'formyl' Ty : A is chosen from the group consisting of alkoxy hydrogen YY carboyl calkoxyearbonyl alkyl analyte; alkyl carbutyl calkylearbonyl aryl carbonyl carylcarbonyl YY alkyl cycloalkylearbonyl heterocyclic Yi carbonyl heterocyclecarbonyl carbonyl $(NZ,Zy)carbonyl (NZ,Z,) and Re Yo choose from The group consisting of a hydrogen hydrogen and a callkyl 74 provided that when Ry represents a hydrogen atom at least one 2 of Ry is Rs or Ry represents a non-hydrogen group Ya Cua for claimant © ?lady Composite = F 1 L by keeping Ry and each of them is selected separately from the group consisting of 7 hydrogens hydrogen and hydroxy hydroxy Re «Rp «Ra ¢ and what is selected each separately from the group consisting of ° hydrogen and halogen and thalogen ‎YAYA Vo. hydrogen Jie "0 Re 1 -71 \ Composite according to the claim dua Yo hydrogen of which hydrogen JS represents Res Ry Ry Y thydroxy stands for Ry 7 hydroxy A stands for 'CH,' Ry: Rp 5 Re sizes, each selected separately from the group consisting of 1 hydrogen and 1 halogen Re v for hydrogen is hydrogen and hydrogen represents hydrogen Re A 1 8 ?- Compound according to claim TO is selected from the group consisting of ; 41-7 -(111-benzimidazolyl (1(myl)piperazin])1(pyridinol (©) ¢6-[4-(1H-benzimidazol-2-ylmethyl)piperazin-1-yl]pyridin- 3-ol £7 "-[(?-methyl-?-pyridinyl (?) piperazinyl))1(methyl]-111-benzimidazole ¢2-[(2-methyl-4-pyridin-2-ylpiperazin) -1-yl)methyl]-1 H-benzimidazole ° Jha Y= (SY) 1 -£-pyridinyl (1)piperazinyl [(V)methyl)-111-benzimidazole l¢2 -{[(2S)-2-methyl-4-pyridin-2-ylpiperazin-1-yl] methyl}-1H-benzimidazole tdi Y= (RY) IT A -pyridinyl piperazinyl ](1(methyl)-111-benzimidazole 2-{[(2R)-2-methyl-4-pyridin-2-ylpiperazin-1-yljmethyl}-IH-benzimidazole 3,1-(41) -7-(111-benzimidazolyl)¥(methyl)piperazinyl])1(pyridinyl (©)) 1methanesulfonamide N-{2-[4-(1H-benzimidazol-2-ylmethyl)piperazin- l-yl]pyridin-3- ylymethanesulfonamide VY or a pharmaceutically acceptable salt thereof. -F compounded according to claim 5 where ¢hydrogen of which hydrogen JS represents Res Ry «Ry Ba Y as ve 'CH, representing L r selected separately from the group consisting of Ros Re Ra (Ra thalogen), halogen hydrogen ° and thydrogen M representing hydrogen 1 alkyl representing Alkyl Ry v Cua compounded according to claim ©? Each of them is selected separately from the group consisting of Re Rp «Ra ¢, a thalogen and a hydrogen halogen (pa 93 ° hydrogen (ag yn Jw) eg 5 Coa Vo for the claimant lady compound - ? “Rp “Ry ° thalogen and halogen hydrogen is hydrogen 1 and 'hydrogen represents hydrogen Rg of hydrogen represents hydrogen Ry A (IV) compound with the formula —£Y \ VATA Voy A Ra 5 and H1 N__X ~~ > A Re joss Rg 5 Rp p (Iv) " where a pharmaceutically acceptable amide, ester amide, or ester salt ¢ is selected From the set consisting of A: Ri Re 5 Ry, x Ra === R 2 A sz” i NTS, 8 Ros oS Rs 4 te y mal JL, and ¢ Rs ¢ 2 xX 3 ¢ Qo” 0 B N Ry ¢ 7 N Ry R2 Ry Ra Re J?OR, al Ra Ce — x AN oN LK v Jo I ~~, TY WA dr, «7 N ¢ BS N ' Rs ~ N TT Rs Rn x x—N Ry Ra 1 - B 1 x x— Sala L N Mtb 3 A x WN As N Ls No Ry ¢ N ' x; N ¢ x N ' Rs ¢ Rs XN R ' 1. Say no all you shell tiles N : JN } x / py 9 ; ASN and AN . Sy . Ps | sy Rs and 5 ; 0 (NH is selected from the group consisting of X 1 CH,CH,CH, «CH,CH, «CH, A to be selected from the group of '1 CH,CH,CH,CH,CH, 5 11 to be selected separately from the group of Rss Ry “Ry” Ry “Ry VY alkyl calkyl alkenyl alkenyl “alkoxy chydrogen Ve “alkylthio VY JX calkylsulfonyl J— su pS alkyl calkylsulfinyl sulfonyl Ve calkylcarbonyl Alkyl Carbonyl calkoxycarbonyl Jui gS Alkoxy calkynyl Alkynyl 8 YAYA Vor VY calkylcarbonyloxy carboxy ccyano formyl VA halogen chaloaltkoxy SS lla chalogen halo <haloalkyl J <li 4 <hydroxy hydroxy alkyl mercapto ¢mercapto nitro (nitro dus (NZ Zp)carbony! (NZ,2,) Js Ss 7 Y , 2 and 7 are selected separately from the Ty group consisting of an alkyl chydrogen calkylcarbony!YY alkylsulfonyl and formyl Ros Re Ro Ro Ra Yr Each is selected separately from the group of 7 chydrogens Alkoxysalkenyl JI alkenyl Abulk Alkyl Yo Sulfenyl Calkylsulfinyl Alkyl sulfonyl Ji calkylsulfonyl various calkylthio 3 alkynyl alkoxycarbonyl Ji «alkoxycarbonyl carbonyl calkylcarbonyl vy alkyl carbonyl calkylearbonyloxy carboxy ccyano formyl chalogen (pasa cformyl YA chaloalkyl JY Ja chaloalkoxy 4 hydroxy Hydroxyalkyl ¢ hydroxyalkyl mercapto emercapto nitro 7 platform 02,22 and carbonyl (: 02,2) 02,2000 where ,7 7,5 each separately selects ry from the group consisting of alkyl hydrogen calkyl alkyl carbonyl to <alkylcarbonyl alkyl sulfonyl and formyl rr is chosen from the group consisting of alkoxy chydrogen vi alkoxycarbonyl alkyl Jl calkyl carbonyl calkylcarbonyl aryl carbonyl carylcarbonyl vo alkyl carbonyl ccycloalkylearbonyl heterocyclic 4 carbonyl heterocyclecarbonyl and carbutyl (NZ Zy)earbonyl (NZ,Z;) Re TV is chosen from the group consisting of hydrogen and the alkyl (TA 7) is chosen from the group consisting of © and 11©; and 2 The bond — present when Z is a carbon atom and not present when Z ¢ is .CH mY 1 Compound according to claim EY Selected from the group consisting of Mekha Vet imidazole rH —[ a ))1(-(pyridinyl) 1) piperidinyl IY Y and ¢2-[(4-pyridin-2-ylpiperidin-1 -yDmethyl]-1H-benzimidazole 3 methyl [-111-benzimidazole (HY) Vm hydropiridinyl SE -phenyl-; (1-7 1 ¢2-[(4-pheny!-3,6-d ihydropyridin-1 (2H)- yhmethyl]-1 H-benzimidazole ° of it. pharmaceutically acceptable salt 1 where £Y is compound according to Claim 4 1 and with each of them being selected separately from the group consisting of Re What Ra 0 thalogen and halogen hydrogen 7 thydrogen hydrogen Jl yum ¢ “CH represents 7 0 and CH bond 777 does not exist when 2 contaminates 1 represents A 7 And R, Rah ,. x mm A compounded in accordance with claim 7; Where -58 1 each separately from the group consisting of Ja “, Ma Re (Rp Ra Y thalogen) and hydrogen halogen 7 thydrogen Jie" Re 1 'hydrogen Jie hydrogen + > (CH, L 1 'CH L 1 'CH Z v (CH) bond <<< does not exist when 7 L 1 'A 4 eraser yoo Ro 2; and FON Ra 01 hydrogen Each represents a hydrogen Res Ry “Ry 1 of element La on a Jai pharmaceutical composition 1-1 or 7; and a non-toxic pharmaceutically acceptable carrier (YO OT) Protection Y . One or more, non-toxic pharmaceutically acceptable carrier 7 .medicament or for use in the form of a drug vo (Y) of the protective element {aa compound 1-1 CH) methyl]- (1) piperazinil ( Y) pyridinyl 1[-7 -48 0001 salt or 2-[(4-pyridin-2-ylpiperazin-1-yDmethyl}-1H-benzimidazole benz imidazole .medicament Or an amide 16 that is pharmaceutically acceptable from it for use in the form of a drug ester (ester 1 p) (1- Y tartrate) (L) the compound where it is a di-48 1 nz imide azole 1 0 - Mel] (1) Pepsirazinyl Y ) piperidinyl ¥ or Maleate 3 [(4-pyridin-2-ylpiperazin-1-yhmethyl]-1H-benzimidazole bis((L)tartrate) 3 imidazole ar HY [de ))1( piperazinyl (Y)a)-(pyridinyl) .2-[(4-pyridin-2-ylpiperazin- 1-yl)methyl]- 1H-benzimidazole maleate °