SA06270015B1 - 1h- imidazole derivatives as cannabinoid cb2 receptor modulators - Google Patents

Abstract

Abstract The present invention relates to a group of 1H-imidazole derivatives that are modifiers of the CB2 cannabinoid receptor, methods for preparing these compounds, new intermediates useful in the synthesis of said imidazole derivatives, methods for preparing these intermediates, and pharmaceutical compositions containing one or more of These 1H-imidazole derivatives as an active ingredient, as well as the use of these pharmaceutical formulations in the treatment of disorders in which the cannabinoid CB2 receptors contribute. And these compounds have formula (I), where R1 to R4 carry the meanings given in the full description.

Description

0# 111-Imidazole Derivatives as Cannabinoid CB, 1H-Imidazole Derivatives as Cannabinoid CB; Receptor Modulators Full Description BACKGROUND (gl SAY) The present invention relates to a group of 1H-imidazole derivatives that are cannabinoid receptor modulators “CB; methods for preparing these compounds; And with new intermediates useful in the synthesis of the mentioned imidazole derivatives. The invention also relates to the use of one of the compounds disclosed 8 herein in the manufacture of a drug with a beneficial effect. The beneficial effect will either be disclosed in this application or will become apparent to a person expert in the field from the specification and from general information available in the field. The invention also relates to the use of one of the compounds of the invention in the manufacture of a drug used in the treatment or prevention of disease or Alls and more specifically; The invention relates to a new use for the treatment of a disease or condition which will be disclosed herein or which will become apparent to a person expert in the field from specifications and from general information available in the field. in the embodiments of the invention; The specific compounds to be disclosed herein are used in the manufacture of a drug useful in the treatment of disorders to which the OB-cannabinoid receptors contribute or which Sar cannabinoid receptors contribute to by manipulating those receptors. Known from International Applications Nos. 8 for F[OITVAY and for the performance of/and evacuation 1]. Derivatives of (Morpholin-4-yl)alkyl-(1H)-imidazole as dependents of the CB receptor have been protected in International application: YV4¢ ro where (Vy N05 4 is specified (example: imidazole 4m) + which discloses three derivatives at position -; “L-phenylalanine derived from carboxamide dc sane containing All of them contain the “1-Aryl-(1H)-imidazole contained in them. The derivatives of the (IH)-imidazole moiety have been protected in US Patent No. 49877498 as active compounds for the central nervous system.

CB; Recent research in the field of selective binding molecules for the receptor ONS © was also reviewed

KH. Raitio et al. (Curr. Med. Chem. 2005, 12, 1217-1237) by “CB, a new receptor that can bind to the 1H-imidazole receptor and surprisingly; Double derivatives of 001 were detected by Jef CB; It includes compounds that have an affinity for binding to the future. ) can bind with much higher affinity to the receptor Led which means CB; For the receptor subtype The compounds included in the invention are either receptor cofactors (CB) or “CB,” or receptor antagonists “CB,” or partial receptor cofactors “CB, receptor (CB) inverse catalysts for the receptor General description of the invention 0 (1) The invention relates to compounds of the general formula iC a 0)

R,

ot — - where: Ri denotes a hydrogen atom or a halogen “ or a cis - alkyl ¢ group where the :0 = alkyl group may contain 1 to ? A fluoro atom “ or has a hydroxy group or an amino + or Ry expressing an alkynyl group - Crs or ic sana © Dohj - alkenyl ¢ where it may contain an alkynyl group - Ci ; or a u-alkenyl group on 1 to fluoro atom oss dy + or 8 expresses a cyclopropyl J acetyl, cyano, methylsulfonyl, ethylsulfonyl, methylsulfinyl, or ethylsulfinyl trifluoromethylsulfanyl or methylsulfanyl or ethylsulfanyl or formyl group 0 alkyl group - Coy heterocyclic. Ry 0 stands for phenyl dc gene. It may have a substitution of 1, 7, “or ; or * from 7 substitution groups; which may be similar or different; and choose from the group consisting of bromo iodos chloros hydroxys ethoxys methoxys propyls ethyls methyl fluoro s, methylsulfonyl s trifluoromethoxy s trifluoromethyl and phenyl s carbamoyl cyano; or Ry expressing the heteroaryl group; where in heteroaryl may be substituted by 1 5 or ? or * from oY substitution groups where 7 has the same meaning as above; Provided that Ro is not a 6-methyl- 2-pyridyl + group or R, denotes a carbocyclic ring system that is fully saturated or has no position fused with a tricyclic, dicyclic or monocyclic saturation cans contains; to 10 atoms; Or Ry stands for fused heterocyclic, tricyclic, bicyclic, or

_oo_

A monocyclic fully saturated or having only one unsaturation site containing ; to 10 atoms;

Where a substitution may occur in the carbocyclic ring system system

heterocyclic ring system with numbers ranging from 1 to © substitution groups

Choose from methyl, ethyl, amino, hydroxy, fluoro ¢ or Ry denotes a © group with the general formula 0112-8 . where Rs denotes a phenyl group that has been substituted b 1 or ?

or © or; or © from the Y substitution groups as defined above; Or Rs denotes a group

heteroaryl or 1,2,3,4-tetrahydronaphtyl group or dua ¢ indanyl group may occur

indanyl group or 1,2,3,4-tetrahydronaphtyl group 4c sess or heteroaryl ic sane substituted in

b 1 or ? or ¥ of the 7 substitution groups as defined above; or Rs denotes a carbocyclic ring system 0 fused to a tricyclic, bicyclic, or monocyclic

The rings are fully saturated or have one desaturation position; it contains ; to 10 atoms; Or M18 crossing

A saturated heterocyclic, dicyclic, or monocyclic fused heterocyclic system

wholly or with one unsaturating position containing; to 10 atoms; where substitution may occur

In the carboxylic ring system or the heterocyclic ring system 08 with a number ranging from 1 to © Cle gana substitution choose from methyl or

ethyl or amino or hydroxy or fluoro" or

Mi stands for methylsulfonylaminoalkyl group or methylsulfonylalkyl group or

acetamidoalkyl group

Ry is a hydrogen atom or a halogen atom + or a formyl group 0 or an alkylsulfonyl or an alkylsulfinyl 0 bitter alkylsulfanyl or

1 = -benzylsulfanyl or cyano ¢ or Ry denotes a “alkyl - Cj group where a substitution may occur in the day alkyl group - Crp ranging from 1 to © from the substituent groups that choose of the fluoro, hydroxy, or amino group; or Ry denotes a group Mi = alkynyl or alkenyl - Cy or of alkanoyl or monel — cycloalkyl or © but - heterocycloalkyl or 1 heteroalkyl - Cog where an optional substitution may occur in these groups B1 to ¥ a methyl ¢ group or an ethyl, amino or hydroxy group “ or B1 to ¥ fluoro atoms; or Ry denotes a phenyl group that has been substituted by a number of 1 to © substituent groups oY where Y has the same meaning as aforementioned; or Ry expresses a heteroaryl group where a substitution may occur in the heteroaryl group with 1 or v SY from 0 oF substitution groups where 7 has the same meaning as previously mentioned; Ry expresses a benzyl group or Cua ¢ heteroaryl methyl Substitution may occur in a benzyl group or heteroaryl methyl group with JY ? or “ of the substitution groups GY Ry expresses one of the two subgroups () or (Thn): ml rr, Ry “=, (i) (ii) VO where Rg expresses for a branched or straight alkyl group or a cycloalkyl group - Cig or an alkyl group - Cp - cycloalkyl group or a heterocycloalkyl group = Cs; - yin and lah or a bicycloalkyl group Cs.io an alkyl Cio hand group - bicycloalkyl or heterocycloalkyl group and - rn - alkyl or tricycloalkyl group or

VY —- for the tricycloalkyl -R - alkyl group or the Wu group Cus «alkyl - Cp - heterotricycloalkyl Substitutions may occur in these groups with 1 to © substituent groups to choose from methyl, hydroxy, ethyl, trifluoromethyl, or fluoro; Or does it express the phenyl group 0 benzyl © or napthyl or phenethyl which are groups that may have a substitution on the aromatic ring system in them with a number ranging from 1 to ? Of the Y substituents previously defined calle with the condition yi, Rg is 2-methylphenyl dc sane ; Or Rg expresses a pyridyl thienyl group sf . Ry is a straight hydrogen atom or alkyl Crp de gana where 0 substitution may occur in the straight alkyl Cre group with a 1 to * fluoro atom ; Or Ry is an isopropyl group. Rg expresses an alkyl Cos ic jana ¢ where it may have a hydroxy or amino group substitution or with a FU) a fluoro atom ¢ or Rg expresses an alkyl Crip group branched or cycloalkyl ion group or heterocycloalkyl ion group or cycloalkyl ion group VO - ure = alkyl or MbE group = alkyl ©: - heterocycloalkyl or wo-bicycloalkyl group or mo-bicycloalkyl group - alkyl ring or tricycloalkyl group w - bur — alkyl or m tricycloalkyl group or m tricycloalkyl group - ring - alkyl or

pain

m alkyl group Cp - heterotricycloalkyl ; They are groups that may be replaced by a number

It ranges from 1 to © of substituent groups choosing from methyl, hydroxy, or ethyl

or amino or methyl hydroxy or trifluoromethyl or fluoro ; Or Rg denotes a group

phenyl may be substituted with from 1 to 0 of the LEY substitution groups previously defined above; Or Rg expresses the group 1,2,3,4-tetrahydronaphtyl § naptyl i.e. indanyl ¢

where a substitution may occur in a naptyl group or .,2,3,4-tetrahydronaphtyl 1 or indanyl b

1 to 1 of the replacement groups?; or Ry is the alkyl group = Cj; = phenyl or

“alkyl - C3 —diphenyl dc sans” substitution may occur in these groups on a ring

phenyl in it with 1 to © substituent groups (YF where 7 has the same meaning as the aforementioned 0; or Ry expresses a benzyl group; Cua substitution occurs in a benzyl group

b 1 to © of the 7 substitution groups; Or Rg expresses a heteroaryl or methyl group

heteroaryl, methyl napthyl, or heteroaryl ethyl ¢ where substitution may occur in a group

heteroaryl or heteroaryl methyl or methyl napthyl or heteroaryl ethyl b 1 to ?

of substitution groups oY where 7 has the same meaning as above; or Ry expressing piperidinyl group 0 or azepanyl or morpholinyl or azabicyclo[3.3.0]octanyl or -4

: is Rg; Provided that it is not pyrrolidinyl or hydroxypiperidinyl

6-methoxy-benzothiazol-2-yl group and no group

¢ [3-chloro-5-(trifluoromethyl)pyrid-2-yl methyl

Or Ry and bpm with the nitrogen atom that bonds to them to form a group

triple, bicyclic or monocyclic heterocyclic; Non-aromatic or aromatic Lisa and saturated

or unsaturated; It contains 7 to 10 atoms per ring; Where substitution may occur in the group

triple, bicyclic or monocyclic heterocyclic; Non-aromatic or aromatic Lion© and saturated or unsaturated with 1 to © substitution groups to choose from

The group consisting of hydroxy alkyl C13 ie methoxy or phenyl § cyano or

« halogen atom or trifluoromethyl halogen atom

Or Ry and O together with a nitrogen atom A nitrogen atom bonds to a hama to form a cyclic group

chases lila) dela] dilate je a 0 (choose from ©; ofS with © to > atoms in the ring; where substitution may occur in the group

Triple, bicyclic or monocyclic heterocyclic. Non-aromatic or aromatic Lisa

saturated or unsaturated by 1 to © of the substitution groups to choose from

The group consisting of an alkyl ie hydroxy or phenyl J amino ie benzyl or fluoro

; Provided that both Rss Ry together with the nitrogen atom to which they are attached have 0 an aza-bicyclo[3.2.1]octany] group substituted with a trimethyl group;

and its stereoisomers (tautomers) and the stereoisomers (Leia N-oxidess stereoisomers), as well as

Salts, hydrates s, and solutes of the compounds of formula (I) mentioned, and their cationic forms

5 and pictures of the stereoisomers and 8G11-010 thereof.

1. The invention also relates to tracers and mixtures of stereoisomers, as well as to independent stereoisomers of compounds of formula (1). In the description of substituent groups, the term alkyl' ' means a straight or branched alkyl group. For example, alkyl Cp means methyl, ethyl, propyl -« ©, or . isopropyl and heteroaryl' "mean monocyclic or conjugated dicyclic heterocyclic aromatic groups; These include, but are not limited to: furyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1,3 ,5-triazinyl, indazolyl, indolyl , indolizinyl, isoindolyl, benzo[b]furanyl, benzo[b]thiophenyl, 1 ,3-benzodioxolyl, dihydro-1,4-benzodioxinyl, benzimidazolyl, benzthiazolyl, purinyl, quinolinyl, AK -2,3 isochinolyl, 1,2,3,4-tetrahydroquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl, chinolyl, phtalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl with the exclusion of the quinolin-2-one group. "chloro ' halogen, fluoro, bromo, or 1600. The expression Tepe = cyclopropyl means "cycloalkyl, meaning cyclobutyl, cyclopentyl 0, cyclohexyl, cycloheptyl, or 010001. It means: cycloalkyl - Cs."heterocyclic" rings containing a (S «O «N] atom are heterocyclic; These include, but are not limited to, fort pyrrolidinyl 5 azepanyl 5 morpholinyl 5 piperidinyl and thiomorpholinyl tetrahydrofuryl piperazinyl and 7A031E700E1608. It is meant by expression

11 = de sens' 0 and bicycloalkyl “cyclocyclic system” including but not limited to ic jane. bicyclo[2.2.1]heptanyl, bicyclo[3.3.0]octanyl or the bicyclo [3.1.1]heptanyl group. de sens' m.m' tricycloalkyl means a three-cycled carbon cyclic system such as the 1-adamantyl, noradamantyl or 2-adamantyl group ©. and "b" means heteroalkyl Straight or branched Mb alkyl groups containing an atom (N) 0; (S) are heterocyclic; they include, but are not limited to, methoxy methyl, dimethylaminomethyl, and ethylsulfanylmethyl. As well as the intervention of prodrugs from The aforementioned compounds within the scope of the present invention.Ye Prodrugs are therapeutic agents that are not active by themselves but are converted to one or more active metabolites.Prodrugs are biotransformable derivatives of drug molecules used to overcome some of the drawbacks to using a drug molecule These constraints include, but are not limited to, JE Jas ALE solubility, permeability, chemical stability, pre-systemic metabolism, and targeting constraints: (Medicinal Chemistry: Principles and Practice, 1994, ISBN 0-85186-494-5, Ed.: F .

D.

Yo King, p. 215; J.

Stella, “Prodrugs as Therapeutics”, Expert Opin.

Ther.

Patents, 14(3), p.

Ettmayer et al., “Lessons learned from marketed and investigational prodrugs 2004, 277-280”, J.

Med.

Chem., 47, 2393-2404, 2004).

101" - Prodrugs; that is, compounds which, when administered to humans by any known route of ingestion, are metabolized to compounds of formula (1); Lad is within the scope of the invention. In particular, this clause relates to compounds having amino groups or primary or secondary hydroxy compounds.Jie can react these compounds with organic acids to give compounds of formula (I) where © leads to an additional group that can be easily removed after ingestion, for example but not limited to amidine or enamine or Mannich base or hydroxyl-methylene derivative ¢ or derivative: .enaminone or amide or ester or carbamate or O-(acyloxymethylene carbamate) the aforementioned compounds in the field of The present invention may contain ge N-oxides as they enter

N- and the rate of occurrence changes. N-oxide or do not increase the metabolites of Tertiary amines

N-oxides in very small quantities transform into a near aphrodisiac. It may be pe oxidation 0

N-oxides or may be less effective. And since (led shld Tertiary amines are more effective than their 7dn:76_ counterparts by chemical methods, this occurs in amines that are easily reduced to approximately eS by the human body in varying degrees. Some 20-0088 are subject to Reductive transformation, and in other cases the reaction occurs in very small degrees or even completely “ted the corresponding Tertiary amines. pay Yo (M.H. Bickel: “The pharmacology and Biochemistry of N-oxides”, Pharmacological

Reviews, 21(4), 325 — 355, 1969) :)

11 - R,]! 0 c-m R, A 3 R, where: Ry expresses a halogen atom ¢ or a d - Cua alkyl group An alkyl group - Ci; may contain 1 to? A fluoro atom “or on a hydroxy group or “amino©” or “Ry” expresses an alkynyl group = Caz or a bur-“alkenyl group where the group may contain a B-alkynyl group or Set 1 Je alkenyl - Cas to ? a fluoro atom; or Ry stands for acetyl group or cyclopropyl or cyano or methylsulfonyl or ethylsulfonyl or methylsulfinyl or methylsulfanyl 0 ethylsulfinyl trifluoromethylsulfanyl or ethylsulfanyl or ic gana formyl | 0 or ic sane cities = heteroalkyl ; Rss Ras carries the same meanings mentioned above. with more customization; The invention relates to compounds of formula (I) AA J and C, in which:

1 - Ry expresses a hydrogen atom or a halogen or a formyl group methylsulfonyl 0 or methylsulfinyl 0 ethylsulfonyl or ethylsulfinyl trifluoromethylsulfanyl or methylsulfanyl or ethylsulfanyl or cyano or Ry expresses an “alkyl = Cig” group where the alkyl - Crip group may contain 1° to ¥ fluoro atoms; or amino hydroxy group “ or Ry expresses a Cr alkynyl group — or alkenyl - Ca. Ca where optional substitution may occur in these groups by 1 to ? methyl group or ethyl group or amino or 1 hydroxy or b 1 to © fluoro atoms ; or Ry denotes a phenyl group in which 0 has been substituted by a number ranging from 1 to © from (Y Janu) groups where Y has the same meaning as above; Or Ry expresses a heteroaryl group where a substitution may occur in 1 heteroaryl group or ? or * from oY substitution groups where 7 has the same meaning as above; or Ry expressing a benzyl or heteroaryl methyl group; Cua substitution may occur in a benzyl group or a 1 heteroaryl methyl group or 1 or ¥ of the \o substitution groups CY Rim expresses a subgroup of formula (i)

_ve - 0 for \>»

Re (ii) Ry - denotes a hydrogen atom, a straight alkyl Cig group, or a dc gens isopropyl ; ° 1.7 _ denotes a Cua “alkyl Cog group in which a substitution may occur with a hydroxy group, an amino group, or b1 to a ¥ fluoro atom, or Ry expresses a branched alkyl Crip group or a ring group cycloalkyl and mon group heterocycloalkyl and Yale group cycloalkyl alkyl - C12 - or min group - heterocycloalkyl - yin alkyl or group with bicycloalkyl or ic seme mon alkyl Ci - bicycloalkyl W group ic tricycloalkyl ic sane galkyl = Cio = 10 mol 4c sane tricycloalkyl and tricycloalkyl — Yb - alkyl or W group “alkyl Cro — heterotricycloalkyl” which are groups in which substitution may occur with a number ranging from 1 to © substitution groups choosing from methyl, hydroxy, ethyl, amino, methyl hydroxy, trifluoromethyl, or fluoro ; or Ry is _ for a phenyl group. It may have a number of substituents ranging from 1 to © from 0 of the 7 substituent groups as defined above; or Ry expressing a napthyl group or 1,2,3,4-tetrahydronaphtyl or indanyl ; Cua substitution may occur in these sets with 1 to * of the 57 substitution sets; Or Rg stands for alkyl group = Cis - phenyl

11 - - or the alkyl group = Cig” diphenyl ; Where a substitution may occur in these groups on the phenyl ring in which it is located by 1 to © from the oY substitution groups where 7 has the same meaning as the aforementioned; or Ry is a benzyl group where a substitution occurs in 1 — benzyl group to © of the 7 substituent groups; or Rg stands for heteroaryl group or heteroaryl methyl© or heteroaryl ethyl where 8 substitution occurs in heteroaryl group or heteroaryl methyl or heteroaryl ethyl group with 1 to ¥ of the substituent groups oY, where Y has the same meaning as above; or Rg expressing a piperidinyl, azepanyl, morpholinyl, azabicyclo[3,3.0]octanyl, 4-hydroxypiperidinyl, or pyrrolidinyl group; Provided that Ry is not a 6-methoxy-benzothiazol-2-yl group nor [3-chloro-5-(trifluoromethyl)pyrid-2-yljmethyl ic gana 01 or Ry and - together with the nitrogen atom nitrogen atom to which they are attached forming a tricyclic, bicyclic or monocyclic heterocyclic group; Non-Ashe or Liga aromatic and saturated or unsaturated; It contains 7 to 10 atoms in the lal wherein the heterocyclic group may be substituted with one or two yo-substituting groups choosing from alkyl, hydroxy, phenyl or trifluoromethyl or a benzyl group or a dc sans di methyl phenyl or a halogen atom ¢ or Rss Ry together with a nitrogen atom that bonds to them forming a saturated monocyclic heterocyclic group; It optionally contains another heterocyclic atom (selected from ofS ON and has from © to + atoms in the ring, where the .Y substitution may occur in the heterocyclic group with a number ranging from 1 to ? of Sle sane replacement that

11 —

choose from the group consisting of alkyl Cra or hydroxy or 1 to ? A fluorine atom

¢ atom

Provided that both B and S are not together with the nitrogen atom that is attached to them

« trimethyl substitution with Lez aza-bicyclo[3.2.1]octanyl ic gana group

Ry 2 and 62 have the same meanings as above. More specifically, too; The invention relates to compounds of formula (1) oh XT RON OR, 0 and in which: Ry expresses a halogen atom ¢ or a d - dua alkyl group may contain 0 group q = 1 Je alkyl to fluorine atom fluoro atom ; or on a hydroxy ¢ group or Rj expressing a group between - an alkynyl 0 group B — an alkenyl or an acetyl or cyclopropyl group or cyano or methylsulfonyl or methylsulfinyl or methylsulfanyl or inter-heteroalkyl group .and expresses phenyl ic gana may have a substitution of 1 or X or a or ¢ or 2 From 0 substituent groups AY may be the same or different; choose from the group consisting of bromo s iodo chloro hydroxys ethoxys methoxy propyl s ethyl s methyl

18 phenyl s carbamoyl s methylsulfonyl trifluoromethoxy s trifluoromethyl s fluoro s monocyclic; Where a heteroaryl substitution may occur expressing a group Ry or + cyano s with the same meaning as the previous; Y where oY or ? or * of the substitution groups 1 b heteroaryl or “6-methyl- 2-pyridyl” is a Ry group provided it is not a tricyclic or a dicarbocyclic ring system expressing a carboxylic ring system Ry © 01 Cyclic or monocyclic is fully saturated or has only one unsaturation position ; it contains ; to denotes a heterocyclic system conjoined with tricyclic, dicyclic, or Ry atoms; or atoms; 01 monocyclic fully saturated or having one unsaturation site; it contains ; To or the carbocyclic ring system where substitution may occur in the carboxylic ring system to © 1 substitution groups with a number ranging from heterocyclic ring system Ve ; Or +[ denotes a fluoro, hydroxy, amino, ethyl or methyl group choose from or ? 1 substituted with phenyl denotes an Rs group of the general formula 11-15 where it expresses the group of Rs as previously defined above; or Y or ? or; or © of the substituent groups where indanyl, 1,2,3,4-tetrahydronaphtyl group, heteroaryl indanyl group, 1,2,3,4-tetrahydronaphtyl group, or heteroaryl group may occur Substitution in set VO expressing system Rs or ? or ¥ from groups | to replace A as already defined above; or 1b fused tricyclic, dicyclic, or monocarbocyclic ring system of carboxylic ring atoms; or f 8 cross 01 loops fully saturated or have one unsaturation position; it contains ; For a heterocyclic system fused with tricyclic, dicyclic or monocyclic saturated atoms; where 01 may be completely substituted or have a single unsaturation locus; it contains ; to 0

101 — - optional in the carbocyclic ring system or the heterocyclic ring system with a number ranging from 1 to ? Substitution groups choose from methyl, ethyl, amino, hydroxy, or a fluoro atom “Rs expressing a hydrogen atom or a halogen atom (pa sila” or dc gamma methylsulfanyl© or a cyano group; or Ry expresses a Cua “alkyl - Cig” group The alkyl - Cig group may contain from 1 to ?a fluoro atom or a group hydroxy, amino ¢, or Ry expressing a Min-alkynyl group or a Cas-oo alkenyl group, where an optional substitution may occur in these groups by 1 to “fluoro atoms”; For a subgroup of the formula (if) 0 0 JL J AR Re NC Rs (i) (ii) 0 where: Ry expresses a hydrogen atom or a group straight alkyl Clg; Rg expresses a min “alkyl group in which a substitution may occur with a hydroxy or amino group or by 1 to ?a fluoro atom ¢ or Ry expressing For the de jie alkyl Cryo group or Vo between the cycloalkyl group or the heterocycloalkyl yl group or the cycloalkyl group alkyl - Ci, — or the Min - heterocycloalkyl - yin alkyl group or the group 7:

ZY. — bicycloalkyl moleline or moleline alkyl group Cio - bicycloalkyl group or Cs.jo tricycloalkyl group - has - alkyl or tricycloalkyl moleline group tricycloalkyl note group — ger - alkyl or alkyl group Crp 7 heterotricycloalkyl Ce.10; These are groups that may be substituted with a number of ©1 to © substitution groups choosing from methyl, hydroxy, ethyl, amino, methyl hydroxy, trifluoromethyl, or fluoro ; or Ry denotes a phenyl group. It may be substituted with a number ranging from 1 to © of the 5 substituent groups as previously defined above; or Rg denotes a napthyl group or 1,2,3,4-tetrahydronaphtyl or indanyl ¢ where a substitution may occur in a napthyl group or 1,2,3,4-tetrahydronaphtyl or 110071 b 1 0 to ? of replacement groups 7; Or Ry expressing a phenyl - yr - alkyl group or a diphenyl - yr - “alkyl group” where a substitution may occur in these groups on the phenyl ring in them with 1 to © from groups replacement; Where it does not carry the same meaning mentioned above; or Rg denotes a benzyl group 0 where a substitution occurs in the benzyl group with 1 to © substituent groups Rg JY denotes heteroaryl 4c sane or methyl heteroaryl 0 or heteroaryl ethyl; Cua substitution may occur in heteroaryl group or heteroaryl ethyl § heteroaryl methyl by 1 to ? of the substitution groups oY where y has the same meaning as aforementioned; or Rg expressing piperidinyl or azepanyl or morpholinyl or azabicyclo[3,3.0]octanyl or 4-hydroxypiperidinyl or pyrrolidinyl group

Provided that Rs is neither the 6-methoxy-benzothiazol-2-yl group nor the [3-chloro-5-] group.

(trifluoromethyl)pyrid-2-yljmethyl

In another special embodiment, the invention relates to compounds of formula (1)

y rT R, (1) ! b what © where in it:

Ry denotes a halogen atom + or group 0 ~ or ; Cua .the alkyl - Ci group may contain 1 to * fluoro atom ; or on the hydroxy group; Or 6 expresses a cyano or methylsulfanyl group «

Ry stands for a saturated carbocyclic ring system

0 entirely or with one unsaturation locus containing © to 1 atoms; in which a substitution may occur with a number of 1 to © substituent groups choosing from methyl, ethyl, amino or fluorohydroxy ; Or ya expresses a phenyl group that has been substituted by 1 or or ? or; or © from the replacement groups; which may be similar or different; It is chosen from the group consisting of methyl, ethyl, propyl, methoxy, ethoxy, hydroxy, iodo s chloro Yo, bromo, trifluoromethyl 5 fluoro, and trifluoromethoxy And methylsulfonyl and carbamoyl and phenyl and cyano « Yvat

YY — Rs stands for hydrogen atom or halogen atom; or ic Ghana

methylsulfanyl or cyano group; or some expressing an alkyl - Cre group; Where may

The Cle - enal - group contains a number ranging from 1 to ¥ a fluoro atom or

Stem ¢ hydroxy group

ORs © for a subset of the form (if) 0 for N >» Rs (ii)

Where in it:

Ba denotes a hydrogen atom. hydrogen atom or methyl group «

fluoro to? A fluorine atom 1, where it may be replaced by an alkyl Cos, expresses the Rg group

00 mah; or Rg denotes a branched alkyl Crip group or a ben cycloalkyl group or a heterocycloalkyl -bo group or an alkyl - Cio = cycloalkyl group or a Mel = heterocycloalkyl -r alkyl group or a bicycloalkyl group Cs.ip or remi alkyl Cy - bicycloalkyl group or mon alkyl group = Cy - tricycloalkyl or C.m tricycloalkyl group or ic sans alkyl - Cj — tricycloalkyl group or C.ip group Co.10 heterotricycloalkyl 0 d alkyl ; These are groups that may be substituted with 1 to © substituent groups choosing from methyl, hydroxy, ethyl, amino, methyl hydroxy, or trifluoromethyl ar fluoro ¢ Or Rg expresses a phenyl group 3%

Yr - _ is substituted by 1 to © of the Y substitution groups as defined above; or Rg expressing a napthyl group or 1,2,3,4-tetrahydronaphtyl or indanyl ; where a napthyl, 1,2,3,4-tetrahydronaphtyl or indanyl substitution may occur in 1 to * of the 7 substituent groups; Or Rg denotes a phenyl group — Bar = alkyl or a diphenyl © group - in - Cua “alkyl Substitution may occur in these groups on the phenyl ring in which it is located by 1 to © of substituent groups (Y where Y has the same meaning as above; or Rg denotes a benzyl group ; where a benzyl group is substituted by 1 to © from the GY Jan! groups or Ry stands for heteroaryl or heteroaryl methyl group or 1 heteroaryl ethyl where 0 or 1 — heteroaryl ethyl heteroaryl or methyl group may have a substitution of ¥ from the substituent groups 7 where 37 carries the same meaning as previously mentioned, provided that Rg is neither a 6-methoxy-benzothiazol-2-yl group nor a [3-chloro-5-(trifluoromethyl)pyrid-2-yljmethyl' group) and with specification More ¢ The invention relates to compounds of formula (1) N Re 0 0 , Ry and Kha 5 where they have:

Ry expresses a halogen atom « or a m0 - Cua alkyl group. An alkyl - Cis group may contain 1 to Ry dor expresses a cyano or a methylsulfanyl group » A fluoro atom Ry expresses a fully saturated monocyclic carbocyclic ring system; © contains + atoms; Or Ry expresses a phenyl group that may be substituted by 1 or ? or "from substituent groups OY which may be the same or different; and is chosen from the group consisting of ethyl 5 methyl, methoxy 5 propyl, ethoxy, hydroxy, chloro, iodo, and fluoro 5 bromo, trifluoromethyl, trifluoromethoxy, methylsulfonyl, phenyl s carbamoyl, cyano ¢ Rg 01 expressing a hydrogen atom or 30 halogen atom (pa sila + or ic gana methylsulfanyl or cyano group; Ry expresses a subgroup of the formula (if) 0 JF N >” Rg (ii) 10 where: Ry expresses a hydrogen atom or methyl

Yo — _ what expresses an “alkyl” selling group in which 1 to 7 fluoro atoms may be substituted; Or Ry expressing a branched alkyl Crip group or a cycloalkyl right group or a heterocycloalkyl group Cs.g or cycloalkyl Cs. ic gana - ir = alkyl or alkyl group Ci - heterocycloalkyl - Cs. or mi bicycloalkyl group or tumor group bicycloalkyl © - yen alkyl or tumor group tricycloalkyl - B - alkyl or Ce. 4c sana D tricycloalkyl or tricycloalkyl Ce.10 ic gana - yer - alkyl or Ce.10 Ae gana heterotricycloalkyl - ar alkyl, which are groups in which a substitution may occur with a number ranging from 1 to © from substituent groups choosing from methyl, hydroxy, ethyl, amino, methyl hydroxy, trifluoromethyl, or fluoro ; or Ry denotes a phenyl group in which 0 may be substituted by a number from 1 to © of the 7 substituent groups as defined above; or expressing a napthyl group or 1,2,3,4-tetrahydronaphtyl or indanyl ; dua a napthyl, 1,2,3,4-tetrahydronaphtyl or indanyl substitution may occur in 1 to ¥ of the 5 substituent groups; Or Rg expressing a phenyl - b - alkyl group or an alkyl - Crs 7 diphenyl group where a substitution may occur in these groups on the phenyl ring in which it is located in b 1 to © from groups The substitution oY where 77 has the same meaning as above; or a benzyl group; where a substitution occurs in group 1 — benzyl to © of the 7 substitution groups . Finally, the invention also relates specifically to compounds of formula (1) in which Ry expresses a fully saturated monocyclic carbocyclic ring system; contains 1 0 0 atoms; or B expresses a group diphenyl is substituted with 1 or ? or ; or o

of replacement groups 7; which may be similar or different; And it is chosen from the group, chloro, hydroxy, phthalate, methoxy, propyl, ethyl, and methyl consisting of, methylsulfonyl, trifluoromethoxy, trifluoromethyl, and fluoro 5 bromo and iodo; The other symbols carry the same meanings mentioned above. cyano, phenyl, and carbamoyl General features of the synthesis: © in several different ways. The choice of the special method depends (I). Compounds with the formula, the suitability of the functional groups and their compatibility with the chemical reagents, Jie, can be prepared on several coefficients of activation and binding of the chemical reagents; And on the possibility of using protection groups; and on the final structural features of the final compound that is prepared, according to known methods. Where relevant references imidazole and ve derivatives can be obtained: a) Gomez-Sanchez etal, J.

Heterocyclic Chem. (1987), 24, 1 757-1763. b) Matsuura et Malac J.

Chem.

Soc.

PerkinTrans. 1 (1991), 11, 2821-6 ¢) Ueda et al., Tetrahedron Lett. (1988), 29, 4607-4610 d) Gupta et al., Eur.

J.

Med.

Chem. (2004), 39, 805-814 Vo e) Van Berkel et al.

Tetrahedron Lett. (2004), 45, 7659-7662 © Haberhauer and Rominger, Tetrahedron Lett. (2002), 43, 6335-6338 Tekha g) Dell'Erba et al, Tetrahedron (1997), 53,2125-2136 h) Lipshutz et al., Tetrahedron Lett. (1992), 33, 5865-5868 mentioned in lel jad of the general form (1) according to SSO and 6 to 1. Diagrams can be obtained from 0 0 0 mi N 10014 © Meek NO, / B’a La Wah Yala = + RCORy);, — = Rs , “Ho 03 1

R,” “NHR, 5 R, any (i (IV) V) hiorinati ; 1 HNR,R,, AlMe;, o | 2060 ing

X

: N

Ho N HNR R, 0 \ HNR;R, oy ry him m l sim ml lm : / 8 3 N coupling reagent | 3"

R, 5

R, 2 (1) wherein X represents

V) subgroup (ii) (Va)

HNMe(OMe) coupling reagent 0 X ry Ld \__N N smooth or RsMgBr R 0 sr. R! - 7 m no : 1 3 N

R,

R, (1) wherein X represents

V1) subgroup (i) o Carry the same meanings as previously mentioned on pages Rg Diagram No. 2) The symbols b to alkyl (C13) express a group of Rigs Ros from? According to the published procedure (IN) _of the general formula Nitroenamine derivatives can be prepared and Gomez-Sanchez et al., J. Heterocyclic Chem. (1987), 24, 1757-1763 by means of ortho-esters s (II) of the general formula Nitroenamine a reaction takes place between derivatives of Ye

M7 _ General (11) to give imidazole derivatives of general formula (IV) (Scheme No. 1). After that, hydrolysis of the sacl ester can be performed, for example, using ithium (LIOH) hydroxide Or NaOH or KOH or 34 to obtain the intermediate alkaline salts of (Sap Cus imidazolecarboxylic acid) converting them to become acidic by using an acid such as aqueous hydrochloride (HCD) to give imidazolecarboxylic acid derivatives of the formula The general formula (V) and an amide group can be added to the compounds of the general formula (IV) by using the amide of the general formula 881111 to turn it into a compound of the general formula (1) in which X expresses a subgroup of it Formula (i) is as already defined above. These group 6 additions can be catalysed using (CH;)3Al (for more on conversions catalyzed with aluminum | 0 to esters to amides see: Levin , E.

Turos, S.

M.

Weinreb, Synth.

Communicate. (1982), 12, 989-993.).1.1. A reaction may occur between imidazolecarboxylic acid derivatives of general formula (V) or their corresponding alkali salts; al amines general formula 0111m188 in order to obtain a compound with the general formula (D) in which X expresses a subgroup having the formula (if) as previously defined 0 above. This particular reaction is preferably performed using activation and binding methods such as active ester formation; or in the presence of a so-called chemical binding reagent; Such as: N'-tetramethyluronium and DCC, HBTU (O-benzotriazol-1 -yI-N, N, hexafluorophosphate), TBTU, HOAt (N- hydroxy-7-azabenzotriazole), PyBOP (benzotriazol- 1 -yloxytris(pyrrolidino)-phosphonium hexafluorophosphate), BOP, CIP (2-chloro-1,3-dimethylimidazolinium hexafluorophosphate), 2-chioro-1,3- Ye

78! - 0 dimethylimidazolinium chloride, PyAOP (-azabenzotriazol- 1- yloxytris(pyrrolidino)- phosphonium hexafluoro-phosphate)

and the like. For more information on activation and linking methods, see: M.

Bodanszky, A.

Bodanszky: The Practice of Peptide Synthesis, Springer-Verlag, New Tetrahedron Lett. (1994), 35, © by York, 1994; ISBN: 0-387-57505-7; b) K.

Akaji et F.

Albericio et al., Tetrahedron Lett. (1997), 38, 4853-4856); d) C.) ;3315-3318 .Montalbetti and V.

Falque, Tetrahedron (2005), 61, 1 0827-10852). A reaction can be made between a compound of general formula (V) or the corresponding alkali salts and a so-called halogenating agent such as thionyl chloride (SOCI2) or oxalyl chloride . This reaction results in the corresponding carbonyl chloride (Ye) of the formula (chloride) 40) of the formula (Va), where it can then react with a compound of formula 1, where Ry and E carry the same meanings mentioned above to give a compound It has the general formula (1) in which X expresses a subgroup of formula (i) as defined above. Such reactions can be catalysed using pyridine or 4-dimethylaminopyridine (DMAP) 01. A reaction is performed between a compound having the general formula N-methoxy-N-methylamine 5 (V) in the presence of a chemical bonding reagent in order to obtain a corresponding N-methoxy-N-methylamine of the general formula (VI) and then A reaction between it and a lithium reagent of the general formula Re-Li or a Grignard reagent to give a compound of the general formula ((); where X Leh expresses a subgroup of formula (i) as previously defined above.

ov. 0 0 N RO N / 1 / LA 8 cl R, + LCHR, — R, N R,

H mi (Vil) (VII) (IV) wherein R, represents -CH,R;

R,-B(OH), 0 A M N B R, (V) have the same meanings as previously mentioned on pages Rs to Ry Chart No.: Symbols In compounds with the general formula -IGZ, the alkyl (Ci3) denotes a Rog «© group to the Y of which an optional substitution has occurred; the R phenyl heteroaryl is defined as the Ry group 12. Cauterizing a Suzuki chemist with what is called a © reagent and a compound having the general formula (VII) from that; a reaction can be made between a compound having the general formula Yas, 0e, bromo, or chloro Jue It expresses what is called a leaving group; L in which is Cus (7111); (VD). It is also possible to conduct a reaction between a compound having the general formula (1). Mesyloxy number scheme for the addition of methylsulfonylalkyl halogenide Or methylsulfonylaminoalkyl halogenide 1 to position number methylsulfonylalkyl group methylsulfonylaminoalkyl group A sodium hydride Jie 3228 It is preferable to conduct such reactions in the presence of imidazole from the nucleus of (VID) in order to facilitate the pet attack The nucleus of a compound with the formula potassium carbonate or Rss -011:84 expresses the Ry group where (IV) is in order to obtain a compound with the formula that carries the same meaning as mentioned above.

1 - Yass from that; A reaction can be made between a compound of general formula (VII) and a compound of general formula 1224-0002 in which Ro expresses a phenyl group or an arbitrary substituent heteroaryl; You know what's called Suzuki's chemical reagent; In order to obtain a compound of general formula 0 av) and compounds of general formula (IV) can be converted to compounds of general formula (El ©) of Scheme 1. Such reactions can be catalyzed by a metal. They are 0 0 0 (R,CO),0 A b" NaNO, gq 0 0 OR — 3 U Ean acetic acid | ORs pyc, H, EtOH HN 1 R, 217 md (X) (Xn (R,CO),0 0 0 o 0 8 : KO-t-Bu Poon, .1 bl 0 HCI NH, Odoi 2 :08 0 HCI 0010 .3 00 0 J og R,NH, RO N 8 1 / — 3 ORs butyronitrile R, N Ri mk HN NR R: 0 (Xh ( Iv) Scheme number: The symbols 1 to Rj have the same meanings as previously mentioned on pages ? to ©; Ros stands for an alkyl (C13) and a reaction can be made between a compound of general formula (IX) and (NaNOp) Jie nitrite derivative for 0 _ to obtain a compound of general formula 00 (scheme *).A reaction between a compound of general formula anhydrides (X) 4 ) of general formula (RICONO) can be carried out in the presence of Reduction reagent such as pd Jie Hiss hydrogen on carbon (0/00) and the like; in an inert organic solvent Jie

+ - ethanol in order to obtain a compound of the general formula (XD) and a reaction can be carried out between a compound of the general formula amine 5 (XT) of the general formula 1821011 in an inert solvent butyronitrile Jie; in order to obtain A compound of the general formula (IV) and compounds of the general formula (AV) can be converted to compounds of the general formula ( ) according to Scheme No. 1. Alternatively, a compound of the general formula ( () can be obtained XD) by conducting a reaction in two phases; from a compound of general formula (XID) and protons can be deprotonated from a compound of general formula (XII) using a strong base such as tert-butoxide (KO-t-Bu) and then A reaction is carried out between it and a compound used to add an acylating group that has the general formula 00, where L led expresses a 0 ferric group such as chloride ¢, then this is followed by treatment with an acid such as ls hydrochloric acid of the like 0 The resulting compound of general formula (XII) 5 anhydride of general formula 00(20,") can be reacted to yield a compound of general formula (XT) 04 ba : LDA Ty 5 Ry” ON 1 Ms 1 Lee Eddy R, R, X represent subgroup (ii Ue X represent subgroup (ii) : 0 Diagram No. 16 The symbols Ry to Rs carry the same meanings as previously mentioned by in pages b who? to ©; and 6 expresses a subgroup having the general formula (if) protons can be removed from a compound of the general formula (I) wherein X expresses a subgroup having the formula (ih) and where the -© position contains a moiety imidazole on a hydrogen atom; using a strong non-nucleophilic base dithium diisopropylamide (LDA) Je then

+ This is followed by a treatment using a group of formula 83-1, in which L expresses a leaving group in order to obtain a compound of the general formula (1), in which 7 expresses a subgroup of formula (ii) and where led The -© position of the imidazole moiety contains R3 substitution groups (Scheme 4). , R, Farrand wren or ern, 0 0 0 9 aE 1) n-BuLi ry A Ay has E + L + 3 2)E-L E 7 R, 3) hydrolysis R, R , R, poe “a stamp named pan Diagram No. 10 The symbols Ro, Saba, and Ros carry the same meanings that were previously mentioned in the pages of Who? to 0 and 2 were derived from an electron affinity slit; AA expresses a leaving group. The imidazole moiety can be converted to have the general formula (IV) in which Ras and Ry represent hydrogen 0 and where Ry has the same meaning as aforementioned; By esterification hydrolysis for example using (LiOH) lithium hydroxide or NaOH or KOH or CsOH in order to obtain the intermediate alkaline salts of imidazolecarboxylic acid (Say converting them to become acidic using acid Such as (HCI) to give imidazolecarboxylic acid derivatives of the general formula (V) and an amide group can be added to the imidazolecarboxylic acid derivatives of the formula (V) in order to obtain a compound of the general formula (( ) where Res Ry expresses

1 — a hydrogen; R7s Roy has the same meaning as above. It is possible to remove protons from this compound of general formula (1) in which Rss Ry expresses Ros “hydrogen” and “bo” has the same aforementioned meaning by using a strong non-nucleophilic base such as: lithium diisopropylamide (LDA) or 1 -007 This is then followed by processing using the E-L© group where. L denotes a leaving group; Jia 160106 or bromide or alkyl =S « and 15 express the affinity group of electrons; Include but are not limited to -5- alkyl or primary alkyl or iodo bromo chloro or cyano in order to obtain a compound of general formula (1) in which X denotes a subgroup of formula (il) and where position -5/7 of slit 100108206 .expresses an E substitution group and/or a hydrogen atom; This depends on the 0 EL group used in this reaction (Scheme no. ©). The definition of group E is part of the definition of group RisRy and does not exceed the definitions of the two groups RisRy previously mentioned 0. Mixtures of compounds can be formed in the last reaction step in Scheme No. E, where they can be separated and purified, for example, using chromatographic methods or using crystallization methods. 0 ° 0 Boro, DE Branch ny R3 Ori 3 [ ° R3 N R, m R, urn en reno 0 Scheme number +: symbols Rg Ro and O Carrying the same meanings previously mentioned in the pages of? to #. A reaction can be made between a compound having the general formula (1) in which Ras Ry expresses hydrogen Ros and Res bears the same meanings mentioned above; and a halogenating agent, N- chlorosuccinimide Jie (NCS) or bromine (Br2) in an inert organic solvent mL dichloromethane in order to obtain Yvat

Yo — - on a compound having the general formula (1) in which Ry stands for CL or Ris Br stands for a hydrogen atom . A reaction can be carried out between a compound having the general formula Cua (I) in which Rs expresses CL or Rpg “Br represents a hydrogen atom and a halogenating agent Jie NCS or in an inert organic solvent mL dichloromethane in order to obtain a compound of the general formula © (I) where Ry led is [© or Rys «Br] is CL or Br (Chart 1 and for more information For detailed information on the nucleophilic compounds, the electrophilic compounds, and the protection group, see: M.

B.

Smith and J.

March: Advanced organic chemistry, p. 275, 5% ed., (2001) John Wiley & Sons, New York, ISBN; 0-471-58589-0) Yo More information on adding and then removing protecting groups during organic synthesis can be found; In: T.W.

Greene and P.G.M.

Wuts, “Protective Groups in Organic Synthesis”, .third edition, John Wiley & Sons, Inc., New York, 1 999 Pharmaceutical-acceptable salts can be obtained using standard procedures well known in the field; for example by mixing one of the compounds of the invention with a suitable acid; Such as an inorganic acid such as hydrochloric acid, or using an organic acid such as fumaric acid. Pharmaceutical Preparations: The compounds of the invention can be formulated into forms suitable for administration; This is done by the usual Te processes using additional materials Jie solid or liquid carrier. The pharmaceutical compositions of the invention can be taken orally, orally, or by injection

into a muscle or into a vein); or by rectal or topical administration. They can be taken as solutions, powders, tablets, capsules (including nanocapsules), ointments (creams or gels), or suppositories. All suitable excipients for such formulations are the usual pharmaceutical solids or fillers, extenders, solvents, emulsifiers, lubricants, flavourings, colourants and/or binders. Sometimes additional substances are used (Says male, mannitol 5 lactose s titanium dioxide s magnesium carbonate, other sugars, talcs sugar alcohols, lactoprotein, gelatin, starch cellulose s and its derivatives, peanut oil or sesame oil. 5 polyethylene glycol, and solvents such as sterile water and mono- or polyhydric alcohols. and more specifically the specific compounds disclosed in this application The types of pharmaceutical formulations that may be used include, but are not limited to, pal AY, chewable tablets and capsules; solutions; solutions for injection; suppositories; suspensions; and types other Ve that are disclosed in this application or that are evident to any person expert in the art from the full description and from the general information in the art.In the embodiments of the invention, a pharmaceutical package or kit containing one or more containers filled with one or more ingredients is presented of one of the pharmaceutical compositions of the invention. This container(s) may be accompanied by various written materials such as instructions for use; or noted in a specific form by a government agency that regulates the manufacture, use, or sale of Ye pharmaceutical products; Where this note reflects the approval of the agency to manufacture, use or sell pharmaceutical products that are eaten by both humans and animals.

- VA Pharmacological methods: Pharmacological experiments conducted in vivo and in vitro related to transmission have already been described in the relevant references. Examples include: (CB neurotransmitter for the cannabinoid receptor e Ibrahim, M.M. et al. (2003) Proc.

Natl.

Acad.

Sci.

USA 100, 10529-10533 e Hanus, L. er al. (1999) Proc.

Natl.

Acad.

Sci.

USA 96, 14228-14233 © e Zhang, J. et al. (2003) Euro.

J.

Neuroscience 17, 2750-2754. e Klein, T.W. et al. (2003) J.

Leukoc.

Biol. 74, 486-496 e Shoemaker, J.L. et al. (2005), J.

Pharmacol.

Exp.

Ther. 315, 08.83 8 e Iwamura, H. et al. (2001), J.

Pharmacol.

Exp.

Ther. 296, 420-425. Measurement of Cannabinoid Receptor Binding Capacity -,013; In vitro 0 the ability of the compounds of the invention to bind to cannabinoid receptors -,03 can be determined; In the laboratory (CHO) was carried out using membrane preparations from Chinese hamster ovary cells as a molecule to which human PHICP-55940 was stably bound to in combination with CB; Transfer of a cannabinoid receptor with the addition or pH]-newly with the binding molecule Sh radioactive. After incubation of a cell membrane preparation without adding the compounds of the invention; The binding is separated and the binding molecule is released © by filtration over fiberglass filters. The radioactivity on the filter is measured by liquid scintillation.

pain

ALE measured binding to cannabinoid receptor-012; in the laboratory

The ability of the compounds of the invention to bind to the cannabinoid receptors “CB2—in

laboratory, using membrane preparations from Chinese hamster ovary (CHO) cells

Stabilized translocation of human cannabinoid receptor 082 with [BH]CP-55940 as a binding molecule.

© Radiant. After freshly incubating the Sa cell membrane preparation with the binding molecule [BH] with the addition of OR

without adding the compounds of the invention; The binding is dissociated and the binding molecule is released

By filtration over fiberglass filters. Radioactivity is measured on the filter

by liquid flash count.

Because of its cannabinoid receptor 02 modulating activity; The compounds according to the invention become suitable 01 for use in the treatment of immune system disorders, inflammatory disorders, multiple sclerosis, allergies, pain, neuropathic pain, and multiple sclerosis disorders.

Lady Neurological Dysfunctional Disorders, Poor or Disordered Strength; muscle contraction or spasm;

tremor, epilepsy, Adal brain injury, stroke, Parkinson's disease,

Alzheimer's, epilepsy, Huntington's disease, apoplexy, stroke (Aad), craniocerebral trauma, spinal cord injuries and disorders

Inflammatory neurological disorders, neurological dysfunction of the neck of the brain, and macular sclerosis

Viral pled infection, myelination-related disorders, and neurological disorders

other; It can also be used to treat cancer, diabetes, and stomach ailments

Lung, asthma, and cardiovascular diseases as well as other diseases in which neurotransmission 0 of the 052 receptor contributes.

- !94+ and the compounds of the invention may be formulated into forms suitable for ingestion; This is done using the usual processes with the help of additives and/or liquid or solid carriers. Dosage: The susceptibility of the compounds of the invention to bind to the cannabinoid receptor 082 has been determined according to © previously described. It is the measured binding ability for a given compound of formula (1); One can estimate the lowest effective theoretical dose. When the concentration of the compound is equal to the measured Ki value, 7009 CB receptors are likely to be occupied by the compound. By converting this concentration into an amount of the compound measured in milligrams per kilogram of the patient's weight, we can obtain the lowest effective theoretical dose; Assuming optimal bioavailability.. 01 pharmacokinetic considerations, pharmacodynamic considerations, and some other considerations may result in changing the dose already prescribed to a higher or lower value of 0. The dose that can be adequately prescribed to the patient ranges from 009 to 0001 mg/kg; Preferably from 0 to 11 mg/kg of the patient's weight. Treatment: The term “treatment” as used herein refers to any treatment of a condition or disease of a mammal, preferably a human; and includes (1) preventing the disease or condition from occurring in an organism susceptible to the disease but not is yet diagnosed as having the disease; (7) inhibiting the disease or condition; i.e. preventing it from developing (7) mitigating the disease or condition; i.e. bringing about a regression of the condition; or (?) alleviating conditions caused by eel mall stop symptoms the disease.

Provide for the detailed description Examples Example No. (1): The materials and methods used

All reactions involving the presence of moisture-sensitive compounds or conditions were performed in a flo© nitrogen atmosphere. Reactions were monitored using thin-layer chromatography (TLC) on silica-coated plastic wafers (Merck precoated silica gel 60 F254) with a dedicated Adal sequencing. ad Ay, was done by UV irradiation Y 2 ¢ (nm) or 0 I and flash chromatogram F indicates purification with a custom silica gels eluate from Acros (070 to v0 yo mm). What is meant by petroleum ether Ve; Petroleum ether 0 to 0 and NMR spectra were determined: (H NMR and °C NMR) in the designated solvent using tetramethylsilane as an internal standard. The chemical displacements were elke in ppm (on scale 8) of tetramethylsilane. The binding constants were given in hertz (HZ) and the peak shapes in the NMR spectra were indicated by symbols “a”. (quadruple) 49 (quadruple double) (triple) dt Yo (triple double) l (twin) dd (dual bi) and and (mono) “brs” (mono-expansive) “ms (multiple). Melting points were recorded using a Biichi B-545 melting point instrument or determined by the differential scanning calorimetry (DSC) method

The yields given refer to the pure products that were isolated.

th

41_ MS/LC preparatory procedure; The equipment used is an electronic aerosol mass spectrometer of the “Sciex API 150 EX” type ¥ a “Shimadzu LCBA LC” pump Shimadzu SCL-10A VP control system a Shimadzu SPD-10A UV meter VP syringe/control device type “Gilson 215 © Phenomenex Luna C18 (2) se sme sequential filter 2a 001 water + formic acid J+) pH = Y IN b ++ acetonitrile ZY + R formic acid see Separation medium with a rate of 1 to 0006© using a compensating flow of 0.7 [de min] ACN 797/6 [HO ZYe ) including (HCOOH 58) scan MS from 001 to 900 atomic units AS in step number 1- and the scan time of the atomic mass unit took 1 second. min) Flow rate (ml/min) a (volume/volume) fea (volume/volume) a a a ee fe qa aaa oe a ee ee Ce ee Te oe 7+4

- 7 For Example No.: Synthesis of Specific Compounds The invention will be illustrated in more detail with the help of the specific compounds whose synthesis RES will now be described and which are intended to be illustrative examples only and are in no way specific to the scope of the invention 0 Other embodiments will be clarified of the invention for those who have experience in the field after reviewing the full description and after the practical application of the invention disclosed in this application. Therefore, there is a determination that the complete description and the compounds contained therein should be mere examples; With reference to one of the real fields of the invention and to the spirit of the invention in the enclosed claims. Synthesis of compound No. (1): Part A: a mixture that was previously stirred by a magnetic method was divided, consisting of Ve g; 2.040 mol (YY,AVO) ethyl 5-methyl-1 H-imidazole-4-carboxylate mol ) in 0.0045 can +,A0) CUL (dse +") +A aa 17,16( phenylboronic acids (vol/vol)); to but an equal part left to react on 1 Yo / ml Qe) ela / ethanol

Vy an hour. After cooling to room temperature, the Te m of parallel AO duration was collected at b part and concentrated_ in the medium of he and the rest_ was purified using flash chromatography Ethylacetate/petroleum ether) 66 m = 1 1 (vol/vol) )) to give: <a©,AA) ethyl 5-methyl-1-phenyl-1 H- imidazole-4-carboxylate 7775 yield).

(t, J = 7 Hz, 3H), 2.47 (s, 3H), 4.40 (q, J = 7 Hz, ? "H-NMR (400 MHz, CDCl3): & 1.42 2H), 7.26-7.31 (m, 2H), 7.48-7.56 (m, 3H), 7.59 (s, 1H) Part B: (CAS 38235-68-6) (-)-Cis-myrtanylamine )20,+ mL dissolved; 0,V m (Use in dichloromethane not VO) Sle mL); to which balkho (01) was added (7.5 mL of ?©m of a solution in heptane + 5, 8 mmol) 0 and the resulting mixture was stirred magnetically for 10 minutes at room temperature, ethyl 5-methyl-1-phenyl-1 H- imidazole-4-1) carboxylate g; mmol).The resulting mixture was stirred at vo C for 10 hours;decanted into an aqueous NaHCO solution;stirred for 0 minutes and filtered over HiFlo.The filtrate was extracted twice using dichloromethane The 0 organic layers were dried with 0,18:50 and LOS filtered in Bf se medium followed by Lan using a flash chromatography 1/7 = To - 0 Ethylacetate/petroleum ether) (vol/ volume)) to give: (Re «SY (RY)] -N - ryl -a 5- gb methyl (gla cyclo[v heptane] 1 1 -?- methyl [ -a - carboxamide —¢— imidazole —HY— phenyl -0- methyl ‎N-[(1R,2S,5R)-rel-6,6- dimethylbicyclo[ 1,1,3] heptan-2-methyl]-5-methyl- 1 -phenyl-1 Yo H-imidazole-4-carboxamide | Compound No. 1) 1.00 g; 775 output). Melting point: ranges from 85 to 84 C.

M4 0 N— H N & X " . N 0 Compound 1 The following compounds from ? to Y were prepared in a similar way: 0 N VY 2 Compound 2 Compound No. ?: Melting point: ranges from 714 to 9171 C 0 Cv has Compound 3 o Compound No.: Melting point: ranges from 157 to 164 C 0 N by 0 2 Compound 4

feo — compound no. tf prepared from .32511-34-5 .R-(+)-bomylamine (CAS) Melting point: range from .7 to 711 C: N Tr ox 5 A Compound 5 Compound #10 prepared from endo-(1R)-1 3,3-trimethylbicyclo[2.2.1]heptan-2-amine © Melting point: range from 1495 To VOT m 0 or HD 4 Compound 6 Compound No. 1 Melting point: ranges from Y4A to Yoo m 1 N N H

5 Compound 7 Compound 7: Melting point: ranges from 337 - 774 m. 0 N 79 2 Compound 8

Synthesis of compound number A

Part A: Then Preparation of A) Ethyl 2-methyl-1-phenyl-1 H-imidazole-4-carboxylate &g;

(J.

Heterocyclic Chem. 1987, 24, 1757-1763) yielded) according to the procedure then described in ZY tricthylorthoacetate s (mol) Ge) ea 1) ethyl 3-anilino-2-nitro-acrylate from

(Vor) © ml). The crude initial product that was formed was purified by flash chromatography (Matt

cascade: diethylether ); (the retention coefficient for sa diethylether is +0) to give pure ethyl 2-methyl-1-phenyl-1 H-imidazole-4- carboxylate in Kuby pa

Ethyl 2-methyl-1-phenyl-1 H-imidazole-4-carboxylate The reaction was carried out between to ead (75, ? g; 017 mol) (in a manner similar to the procedure previously described for compound no.

V,Y) AlMe; 1) 0 ml of? A molar of a solution in heptane is 6 044 mol) and 1017 pa 7 (©) 1-adamantane amine mol). The crude initial product that was formed was purified by flash chromatography (eluaterate: diethylether); To give: Zee «pa Y,Y) N-adamantyl-2-methyl-1-phenyl-1 H-imidazole-4-carboxamide product). Melting point: ranges from 707 to 701 C. 0 pr A H Compound 9 vo Compound No. 4: Prepared in a similar way to Compound No. 6 from:

()-cis-myrtanylamine (CAS 38235-68-6) Melting point: ranges from 114 to NIV C. 0 N re 4 Compound 10 Compound No: 01 Dissolved: +,¥Y) N-Adamantyl-2-methyl-1-phenyl-1 H-imidazole-4-carboxamide g b © mol) in tetrahydrofuran no YO ( Se ml). The resulting solution was added slowly to a solution of lithium diisopropylamide (©7, mL of ?mol of a solution in heptane (THE 07# mol) (LDA) in an Np atmosphere at -Vo M. A solution of methyl iodide (the vee) can mol) was added in THF not Sle and the resulting solution was stirred for an hour at -Ve m. The dead solution was left to room temperature and stirred for another two hours 0 then it was quenched by Sl acetic acid and after concentrating in vacuo; The resulting residue was purified using flash chromatography with 1 = (-40) petroleum ether | diethylether (v/v)) to give compound No. 01 and compound No. 11, respectively. The melting point of compound number Ne ranges from YA, to YAY m 0 N VE 2 Compound 1

M4 - Compound No.: 11 was prepared more efficiently by reaction: ethyl 2,5-dimethyl-1- phenyl-1 H-imidazole-4-carboxylate (compare it with the corresponding methyl ester in step JV In the reference 1757-1763, 24, 1987 “(J.

Heterocyclic Chem. With the excuse 1-adamantane-amine.

HCI ¢ according to Weinreb's procedure for adding the amide group of © . has previously been described in this application in respect of Compound No. 1 Part B. Melting point: ranges from 700 to 7064 C. Synthesis of Compound No. 11 Part A: Ethyl 2,5-dimethyl-1-(3-methoxyphenyl)-1 H-imidazole-4-carboxylate was prepared in a manner similar to glad 0 described in: Heterocyclic Chem. 1987, 24, 1757-1763 0 of: ethyl 3 -(3-methoxyphenylamino)-3-methyl-2-nitro-acrylate and triethylorthoacetate Part B: amide group added to: Ethyl 2,5- dimethyl-1-(3-methoxyphenyl)-1 H-imidazole-4-carboxylate (in a manner similar to 0 _ to the procedure previously described in this application for compound No. 1 (and stirred at a Ve for dela 1 using ALMe; and (38235-68-6 (-)-cis-myrtanylamine (CAS) to give compound number NY Melting Point: ranges from 157 to 100 C.

0 1 < x for A 0 0 Compound 12 in a similar way 01 to 17 and the compounds were prepared from 0 0 0

N— H N N

N H N - H = N H =

CR || A1

H

0 HCI 0 0

Compound 13 Compound 14 Compound 15 Melting point: ranging from Melting point: ranging from Melting point: ranging from A Yon Halam 64 Um 6 0 0 o Aqb N N NS

N H N H N H oD + FG b Compound 16 Compound 17 Compound 18 Melting Point: From | Melting point: ranging from 1 Melting point: ranging from EM 77 C = YN AVE 1 0 0

N N

TS JT VD

2 1 2 0

Compound 19 Compound 20 Melting point: ranging from | Melting point: ranges from d = 118 a YAM = VAY

Yvia¢

This © _— Ma Liu compound Y 1 part A: to a previously stirred suspension of: 064 Y (0.1 mol) in 7 anhydrous; (NaH) sodium hydride (£,AA) g from 760 suspensions was slowly added; 107 mol) and the resulting mixture was stirred at room temperature for ¾ min. and ¥,A) bromide benzyl a AY mol) was slowly added; The reaction of the resulting mixture was continued for VT 1 hour. Water was added to the mixture. The organic layer was separated from the water layer. The aqueous layer was extracted three times using 60371866816. The organic layer was dried using MgSO, filtered and concentrated to give an oil. The resulting residue was purified (in order to separate the two domain isomers that were formed) using a flash chromatography 0 (gradient amount of ethylacetate / diethylether) to give: “an 1114( ethyl N-benzyl-5-methyl-1H-imidazole- 4-carboxylate 49 7 product). 3H), 2.45 (s, 3H), 4.37 (gq, 1-7, 2H), 2' H-NMR (400 MHz, CDCl,): 6,127 A) 1.40 (s, 2H), 7.03 -7.08 (m, 2H), 7.28-7.38 (m, 3H), 7.48 (s, 1H). 5.10 Part B: Jeli made between ethyl N-benzyl-5-methyl-1H-imidazole- 4-carboxylate (1,0 (an No) (1001+ mol) and (VY), adamantyl-1-amine.

HCI J0047 mol) AL(CH3)ss Yoda £7) molar in (Use +,++4Y « hexane in (Je Y+) 1,2-dichloroethane at 70 °C for £1 h according to the procedure described for Compound No. 1 Part B. Purification was carried out using flash chromatography (V/V = Ethylacetate/petroleum ether)

— ©1

YAY Melting point: ranges from 0. or

Compound 21 using a similar method, YY YY, and the compounds were prepared from 0 solutions H wg

N§

SY

—S-N

Oh H

Compound 22.

YY Synthesis of Compound No.: By linking YY, Compound No. 3-(methylsulfonylamino)propyl chloride with ethyl 4-methyl-1 H-imidazole-5- carboxylate was prepared h; Then, Yo was separated at 0m for DMF using ,6:00 as a base in Ve methanol / ethylacetate) the two band isomers that were formed using flash chromatography.

oY - — 1 /a = (volume/volume)); This was then followed by a catalytic process with AL(CHj3)3 to add amide Ac gana using (-)-cis-myrtanylamine compound YY. Melting point:_ranging_ from +4 to 018 um;_holding coefficient LYS 1 /¢ = MeOH/EtOAc (volume/volume). 0 N Nw ne 1 5 N 3S 1 endo H 0 Compound 3 . Compound ?7: Prepared from: endo-(1 R)-1,3, 3-trimethylbicyclo[2.2.1]heptan-2-amine) Melting point: ranges from 4 to 107 °C. Custody coefficient 1/4 = MeOH [EtOAC) 0.4 (vol/vol). Synthesis of compound No. 0 VE part A: to a previously stirred solution of: aa A) ethyl N-benzyl-5-methyl-1 H-imidazole-4-carboxylate 0745 _ mol) in 0) methanol ml); A solution of V,¥) KOH g was added slowly; VY eli J Ae mol) and the resulting mixture was heated at 860 °C sad 2 hours. The solution was cooled to room temperature; Then concentrated HCI (9,Y mL) was added. The precipitate formed was collected by filtration

1 e to give methanesulfonic acid 1-methyl-piperidin-2- ylmethyl ester (/l "g 791 yield). YAY leat point (decomposition). Part B: to a magnetically stirred solution of: ethyl 4-methyl-1 H-imidazole-5-carboxylate (7/a g 071 mol) in anhydrous acetonitrile (YO) ml); sequentially “Je (1,7) has been added diisopropylethylamine (DIPE[Xi]A) 7 mol) 5 A) HBTU 4 gray 0.77 mol) 5 methoxy-methylamine (1¥,¥ 1.0777 µmol). The product was then concentrated at 71 C for 11 hours and then concentrated in culture medium The resulting residue was dissolved in ethylacetate and then washed with aqueous solution of NaHCO 75 and water The organic layer was dried using MgSO, filtered and concentrated The resulting oily residue was purified using flash chromatography (cthylacetate / Y/Y = acetone (vol/vol)) to give: N-methoxy-N-methyl-5-methyl-1- benzyl-I H-imidazole-4-carboxamide (/excluding 0 g 7 yield). (s, 3H), 3.47 (s, 3H), 3.77 (s, 3H), 2401 = 260.” H-NMR ( 400 MHz, 08 2.34 (s, 2H), 7.05-7.10 (m, 2H), 7.18-7.28 (m, 3H), 7.48 (s, 1H). Vo 5.09 Part C: to a previously stirred solution of 4)1-naphtylmagnesium bromide ¢ 1.75 a molar in 100177 (THF mol); A solution consisting of [:

_ 4H — (Y,74) N-methoxy-N-methyl-5-methyl-1-benzyl-1 H- imidazole-4-carboxamide g 06 mol) in anhydrous THF (da 1) The resulting solution was stirred for 1 hour.The Jeli mixture was quenched in 1 M (de YY) HCl and then extracted with ethylacetate (EtOAc) and the EtOAc layer was washed twice with water; dried with MgSO; / dichloromethane) = 1/49 (vol/v) to give compound 9 crude 1 Yo) g; + / output) in zrite image. 2.58 (s, 3H), 5.12 (s, 2H), 7.08-7.13 (m, 2H), 7.31-7.40 2113-1114 (400 MHz, 0585 (m, 3H), 7.44-7.56 (m, 4H), 7.78-7.82 (m, 1H), 7.84-7.89 (m, 1H), 7.92-7.96 (m, 1H), 01 8.16-8.22 (m, 1H).0 1 ~ 3

Compound 24 Synthesis of compound number YO Compound number YO was prepared in a similar way from: N-methoxy-N-methyl-5-methyl-1-phenyl-1 H- imidazole-4-carboxamide Vo in diethylether anhydrous). Purification was performed using flash chromatography (methyl-tert-butyl ether).

A 00 _— 1 = petroleum ether 9 (vol/vol)) of the crude precursor that has been isolated to obtain compound number Y¢ (Yo/product) in the form of a pale yellow oil. 0

Compound 25 YO (m, 3H), 1.25-1.47 (m, 6H), 1.70-1.80 (m, ?'H-NMR (400 MHz, 0068 o 0.86-0.94 2H), 2.50 (s, 3H), 3.04-3.11 (m, 2H), 7.26-7.32 (m, 2H), 7.50-7.59 (m, 4H). Compound number YT was prepared in a similar way. 0 “Mr 2 Compound 26 Compound No. 776 Cf (dichloromethane / methanol) = 597/7 (vol/v); silica gel 11 ( = M, 2 Je) Synthesis of compound No. YV to a solution previously stirred magnetically consisting of:

— 1 e_

aa), TY) N-(adamant-1-yl)-1-phenyl-1 H-imidazole-4-carboxylate 2+ 50+ mol) in

(Je 0 ) dichloromethane solution of «:3 +,0Y) was added filling; ©0000 Milli

Baal ml). The reaction of the resulting mixture continued at room temperature (©) dichloromethane in (J se

; hours. And it was done Addition of dichloromethane and a 70% aqueous solution of NaHCO to the reaction mixture. The separated organic layer was dried with MSO; filtered and concentrated

in a vicious medium. The resulting residue was purified using dichloromethane flash chromatography

1/11 = acetone / (volume/volume). Then it was recrystallized from acetonitrile to give:

1 g; 0011 ) N-(adamant-1-yl)-5-bromo-1-phenyl-1 H-imidazole-4-carboxamide

output). Melting point: ranges from YY to 777 C. 0 N N 5 N " Br

Compound 27 y.d.

Compound number YA was prepared in a similar way with a yield of 701 using:

N-chlorosuccinimide (NCS) as a chloro adducting agent for 400 hours at room temperature.

Purification was done using a flash chromatogram with 1/1 = acctone | dichloromethane).

(size/size)). Vo melting point: ranges from 0084 to 17°C

Lah 0 N WLS Cl 8« Compound 28 Synthesis of compound No. 14 to a pre-stirred solution of: N-(adamant-1-yl)-5-bromo-1-phenyl-1 H -imidazole-4- carboxylate (+1 gram) in 01 (dichloromethane © ml); A solution of Bry (+ mL) was added in : dichloromethane (© mL) +,YV) triethylamine s mL). The reaction mixture continued at room temperature da for 50 hours. Dichloromethane and a 70% NaHCO solution were added to the reaction mixture. The separated organic layer was dried with MgSO; filtered and concentrated in vacuo. The resulting residue was purified using a Ye flash chromatography 0 ( dichloromethane) then stirred in diethylether and filtered to give: (p > +,Y4) N- (adamant-1-yl)-2,5-dibromo -1-phenyl-1 H-imidazole-4-carboxamide Melting point: ranges from YYA to 771 °C. 0 N N H TVS Ps Br Compound 29

OA — - Compound 0 was prepared in a similar way with a yield of 777 from: N-(adamant-1-yl)-5-chloro-1- phenyl-1 H-imidazole-4-carboxylate using: N -chlorosuccinimide (NCS) is a chlorinating agent. Melting point: ranges from VAY to a 68 0 N N H + on 0 Compound 30 5 Synthesis of compound No. 31 to a previously stirred solution of: N-(adamant- 1-yl)-2-methyl-1-phenyl-1 H-imidazole-4- carboxylate ( , “an 5 (Use in THF anhydrous Vo) mL) in an atmosphere of Np at ip Vom a solution of “0 ) diisopropylamide (LDA) mL of ? molar of a solution in “THF / heptane” 04 mol (LDA) in an atmosphere of Ny at cp Vom and the resulting solution was stirred for one hour. A solution of “aa 1,17) para-tolylsulfonyl cyanide was added 0909© mol) in anhydrous THF 01 (mL); the resulting solution was stirred for 1 hour at oom and left to come to room temperature and stirred for another hour VY and then quenched with water. The mixture was extracted using diethylether, and the organic layer was dried using MgSO

©9 - filtered and concentrated in vacuum. The resulting residue was purified using 1/19 = acetone | flash chromatography dichloromethane (vol/vol) ); Then it was recrystallized from acetonitrile to give compound No. 3 9 11 can 0 , Y / product). The melting point of compound No. 7 ranges from YER to YEA m. 0 A N° CN Compound 31 ° Compound No. YY was prepared in a similar way with a yield of 771 from: N-(adamant-1-yl)-2-methyl-1- phenyl-1 H- imidazole-4-carboxylate with dimethyldisulfide (CH3SSCH3) Melting point: 177 to 177 °C. 0 TS “SCH, L” Compound 32 0 Compound No. YY was prepared in a similar way with a yield of 7748 from: alaaiulyN-(adamant-1-yl)-2-methyl-1- phenyl 1-H-imidazole-4-carboxylate: para-tolylsulfonyl cyanide. The melting point ranges from 711 to TIA C.

0

FD

N°Cl

Compound 33: In a similar way from IVY, Compound No

N-(adamant-1-yl)-2-methyl-1-phenyl-1 H- imidazole-4-carboxylate using para- tolylsulfonyl bromide M. YEE Melting point ranges from 747 to © 0 A A Br

Compound 33A: In a similar way with a power yield of 717 of VE, a compound was prepared: using N-(adamant-1-yl)-1-phenyl-1 H- imidazole-4-carboxylate M.YY to YYY Melting point: ranges from Lpara-tolylsulfonyl cyanide 0

N

N H

CN

Compound 34 years old

11: from AVY and compound © was prepared in a similar way with a power yield: using N-(adamant-1-yl)-1-phenyl-1 H- imidazole-4-carboxylate M.VTA to 116 Melting point: ranges from dimethyldisulfid (CH;SSCHS) 0

N

N H

hd

H,CS 2

Compound 35 Stirring it magnetically is mol) while preserving 1.09 aa VV,Y) 2-hydroxyimino-3-oxo-butyric acid methyl ester (ml) and 171) and after stirring the mixture for two hours; water was added a © temperature below, and then the organic layers were washed diethyl ether The resulting mixture was extracted twice using 0 aqueous concentration of 75. The layer NaHCO; It was well filtered and concentrated to give the raw “MgSO, organic using color ae g) in the form of YE oil) 2-hydroxyimino-3-oxo-butyric acid methyl ester, as it was not purified again. 2.42 ( s, 3H), 3.91 (s, 3H), 9.90 (br s, 1H).?'H-NMR (400 MHz, 085 yo)

17- For Part B: Crude: 2-hydroxyimino-3-oxo-butyric acid methyl ester (4 7 g; about 1.19 mol) was dissolved in a magnetically stirred mixture (Je YAY ) acetic acid, (Je YY +) acetic acid anhydride, 00/© (; g); The resulting mixture was hydrogenated for 1 hour at room temperature at a pressure of 1 atm of Hy. and after filtering over Hiflo; Acetic acid and acetic acid anhydride were removed by concentration in buffer medium & Cd g. Purification of the resulting crude mixture using flash chromatography (c/a© = methanol / dichloromethane) (vol/v)) to give: (V1,V) 2-acetylamino-3-oxo- butyric acid methyl ester g; Zh is produced) as a white solid. The retention coefficient (methanol / dichloromethane) - 0/15 (vol/vol)) = 1 . 0 8 : AAS (s, 3H), 2.40 (s, 3H), 3.83 (s, 3H), 5.29 (d, 1-7, 21-1118 (400 MHz, 2.08 1H), 6.71 ( br s, 1H). (de Y,A4) trifluoroacetic acid (Je ¥,2Y) aniline and the resulting mixture Ve was heated on reflux for £0 min. A butyronitrile was removed in vacuo at room temperature; The resulting residue was dissolved in dichloromethane and washed twice with a solution (ste potassium carbonate) and the organic layer was dried with MgSO, filtered, and concentrated in vacuo. The resulting residue was purified using flash chromatography) diethyl 1/ 4 = acetone / ether (volume/volume) to give:

Ye ) methyl 2,5-dimethyl-1-phenyl-1 H-imidazole-4-carboxylate g; Zen output). (s, 3H), 2.33 (s, 3H), 3.91 (s, 3H), 7.18-7.22 (m, ?'H-NMR (400 MHz, CDCl): § 2.22 2H), 7.51-7.59 ( m, 3H). Ml); A solution of 11011 VTA (g) in 100 (ele) was added. The resulting mixture was heated at Ve for 16 hours; The dead was left to room temperature and acidified using ? Molar of 1 N equivalents of 1101 solution. The precipitate formed was collected to give crude: (V,+) 2,5-dimethyl-1-phenyl-1 H-imidazole-4-carboxylic acid (0 g 797 yield). (s, 3H), 2.43 (s, 3H), 7.56-7.61 (m, 2H), 7.66-? H-NMR (400 MHz, 0150-5 2.31 (m, 3H). 7.71 Part E: to a previously stirred solution of: can +7) 2,5-dimethyl-1-phenyl-1 H -imidazole-4-carboxylic acid 0.0074 mol) in VO) acetonitrile 0 mL); to which diisopropylethylamine (DIPE[Xi]A, H[upsilon]nig's base) was added sequentially (NO PEN and O-benzotriazol-1-yI-N, N, N', N'- tetramethyluronium hexafluorophosphate (HBTU) (an 71, V,+0) (-)-cis-myrtanylamine filling (Jse + 40 + YA and the reaction of the mixture continued g y

The product was heated at YoC for 11 hours, then concentrated in fhe medium, the resulting residue was dissolved in dichloromethane, washed with 0/5 aqueous NaHCO, and the organic layer was dried using MSOs were filtered and concentrated in vacuo. The resulting residue was purified using flash chromatography (methanol / dichloromethane) = mH© (vol/vol)) to give: N-[(1R,2S,5R)-rel-6,6- dimethylbicyclop[1,1,3] heptan-2-methyl-2,5-dimethyl-1-phenyl-z I H-imidazole-4-carboxamide z (compound 96) can +,V) 797 product). methanol / dichloromethane / silica gel) Ry = mah (vol/vol)) about 0.1 0 2 d N i H 2 Compound 36 0 and compounds from TY to £Y similarly to 0 N 0 Compound 37 Yva¢

~ Yo — vy Compound 1.26 (t,7=7,3H), 2.41 (s, 3H), 2.56 (q, J = 7, 2H), 211-11 (400 MHz, 0085 7.23-7.28 (m) , 2H), 7.49-7.60 (m, 6H), 7.66 (d, J = 8, 1H), 7.88 (d, J = 8, 1H), 8.11 (d, J = 8, 1H), 8.28 (d, J = 8, 1H), 9.85 (s, 1H).

HH

SU

2 HCI

Compound 38 o Compound 8©: Melting point: 1179-179 m.:

Nio

N H

2 Compound 39 Compound 795: Synthesized from endo-(18)-1 ,3,3-trimethylbicyclo[2.2. 1]heptan-2-amine Melting point: ranges from 101 to 1101 C (decomposition).

- 11 l: N ih N l lal 2 Compound 40 Compound 560: Prepared from .endo-(1S)-1 ,3,3-trimethylbicyclo[2.2.1]heptan-2-amine 6 bits: (s, 3H), 0.96 (t, J = 7, 3H), 1.12 (s, 3H), 1.17-1.27 2111-14 (300 MHz, 0.89 (m, 5H), -1.40 1.60 (m, 2H), 1.67-1.81 (m, 3H), 2.15 (s, 3H), 2.70-2.95 (m, 2H), 3.78 (dd, J ~10 and 2, 1H), 7.18-7.23 (m, 2H), 7.34 (br d, J ~ 10, 1H), 7.48-7.57 (m, 3H).© 0 0 0 nm N N N N $)ci N CH 1 ] H A | 1 A CF, 2 of 5 1 of |O 0 | © Compound 41 Compound 42 Compound 43 Melting point: ranging from Olga point!: ranging from Melting point: ranging from 1 = 41 C (decomposition) Var - 14% C (decomposition) = 158 1710 CE (decomposition) 0 N CF pn z 2 Compound 44 7+6

— Vv = 4 m - VT melting point: range from EE compound 0 N N=

Eng

A

Compound 45 . R-(+)-phenethylamine ©4: prepared from 1.58-1.61 (m, 3H), 2.17 (s, 3H), 2.33 (s, 3H), 5.25-5.35 ?'H-NMR (300 MHz) , CDCl3): 6 (m, 1H), 7.15-7.54 (m, 11H). © 0

N N

Se to AN

Compound 46 C 161 to 14 Compound 16 Melting point: ranges from 0 wot 1 a 3

Compound 47

Yvat¢

- 697 : 18 Compound 1.10 (s, 9H), 1.69 (s, 3H), 2.24 (s, 3H), 7.00-7.06 (m, ?'" H-NMR (400 MHz, CDCls): 8 2H ), 7.46-7.55 (m, 3H), the NH peak is invisible and probably merged with the H,0O 1.60.7peak at 6

(EAB) Synthesis of compound ©: to a magnetically stirred solution of (mol) in ©0005 can +11) 2,5-dimethyl-1-phenyl-1 H-imidazole-4-carboxylic acid ¥,1 ) diisopropylethylamine (DIPEA) mL); Sequentially Yo) dichloromethane and (p > Y,00) CIP (2-chloro-1 ,3-dimethylimidazolinium hexafluorophosphate) (Je g; ©0077 mol) were added. The reaction of the resulting mixture (+, Y) 3-hydroxyadamantane amine Ye continued for an hour; It was then concentrated in vacuo. The mixture 11 was dissolved at 17°C for an aqueous period of 10% and NaHCO was dissolved. It was washed with the dichloromethane solution produced in, filtered and concentrated in vacuo. MgSO was purified, drying the organic layer with (16 = methanol / dichloromethane) the resulting residue using flash chromatography: (vol/v)) to give 0

N-(3-hydroxyadamant-1-yl)-2,5-dimethyl-1- phenyl-1 H-imidazole-4-carboxamide "(vol/vol)) /18 = methanol / dichloromethane / silica gel) Ry Yield).ZV Lan J °) 771 C. Melting: ranges from 51? to Ai, approx.

_ 5 ed 0 " + 1 A g OH Compound 48 Compounds from £9 to +4 were prepared in a similar way 0 0 pes for N H | | 8 x x End Compound 49 Compound 50 Point | of fusion: tetrao z of YoV — Yoo m 1 point of fusion: tetrao z of 4 — 7 m 0 sun ing 1 N racemic,endo 0 Compound 51 © Compound 1: Then it was prepared from racemic endo-2-amino-bicyclo[2.2.1Theptane (m, 8H), 2.13 (s, 3H), 2.21 (br s, 111(, 2118 (400 MHz, 101150-86 0.85-1.64 (s, 3H), 2.40 (br s, 1H), 4.07-4.16 (m, 1H), 7.34 (br d, J ~ 8, 2H), 7.40 (br d, J ~ 7, 2.24 1H), 7.52-7.61 (m, 3H). 74p.

‎VY. = L 0 1 B .0 A Compound 52 Compound 7©: Prepared (from:(noradamantylamine) Melting point: ranges from VEY to 1 0 M ts FANE F oC CC ||| CR A 27 Ct 2 Compound 53 Compound 54 Compound 5 Melting point: ranging from 1 Melting point: ranging from 1 Melting point: ranging from a IY - 11 ap Yov = Melting point: From 1 Melting point: From 1 Melting point: From YE a VAY = VA — ct aXe = YiA 74p

: — except 0 N solution N 1 |] 1" HH z CF, 0 Compound 59 Compound 109 (s, 3H), 2.43 (s, 3H), 7.23-7.27 (m, 2H), 7.55-7.60 ?'H-NMR (300 MHz, 08 2.28 (m, 3H), 7.79 (dd, J =9 and 2 Hz, 1H), 8.22(d,J=9 Hz , 1H), 8.42 (s, 1H), 8.62 (d, J ~ S Hz, 1H), 8.94 (d, J = 5 Hz, 1H), 10.25 (brs, 1H). 194.5 m (decomposition).0 N CN Enda WJ 5 Compound 60 eS yall (s, 3H), 2.43 (s, 3H), 7.23-7.27 (m, 2H) ), 7.54-7.60 ?'H-NMR (300 MHz, CDCl;): & 2.29 (m, 3H), 7.70-7.76 (m, 2H), 7.95 (d, J = 8 Hz, 1H), 8.17 -8.21 (m, 1H), 8.27-8.29 (m, 01 1H), 8.63 (d, J = 8 Hz, 1H), 10.20 (br 8, 1H). Melting point: YEY,0 m (decomposition).

� — VY _ 0 z ! [17

Compound 61 Compound 11: Melting Point: Ranging from 1779 - 1777 C 0

N

Oe

N

0

Compound 62 petroleum [diethyl ether] 5 111 Compound 7+: Melting point: about 0.01 (vol/v)) about 1/1 = ether © 1.66-1.78 (m, 6H), 2.08-2.18 (m, 9H), 2.19 ( s, 3H), ?'H-NMR (400 MHz, 0655 3.22 (s, 3H), 4.59 (s, 3H), 7.06 (br s, 1H), 7.25-7.30 (m, 2H), 7.47-7.55 ( m, 3H) 0 © 2

HCI

0 oS Compound 63 (1739 m - YY) Compound 17: Melting Point: Range from

A 1 0 CF 5 A F SA N 0 Compound 4 | Compound 14: Melting Point: Ranging from 170 to 1177 C. Synthesis of Compound No. 169 Part A: To Suspension Above Mechanically agitated is: 2,5-dimethyl-1-phenyl-1 H-imidazole-4- carboxylic acid ~~ © (+, 4 g; 0.88 mmol) in (Ja ¢ ) CHCl 0 Ve ) oxalyl chloride added g; maghara millimol); The reaction of the resulting mixture was continued at OA Aa py C for 2 hours; It was then concentrated in vacuo. The resulting mixture was dissolved in dichloromethane; YA) diisopropylethylamine was added, + g; 7,448 mmol). A solution of -2,3-dichloroaniline (70," g 0 14700 mmol) in "(Je©) dichloromethane was slowly added to the resulting mixture; The reaction of the resulting mixture continued for two hours at room temperature; Then it was concentrated in vacuo. The resulting residue was purified using dichloromethane flash chromatography to give: “Yi) N-(2,3-dichlorophenyl)-2,5-dimethyl-1-phenyl-1 H-imidazole-4-carboxamide g; 777 output). Melting point: ranges from 1117 to 76 C.

— Vs — and CI ci

N rr

A

Compound 65 was prepared in a similar way: YA and compounds from “6 to 0 rH N_) 4 were prepared

Compound 66 M1118 = 1177 Compound 16: Melting point: ranges from 0 2 2

Compound 7 o

A IYO - NYY Compound 17: Melting point: ranges from 0

N N -N ATX N 0 0 Compound 68

— Vo — : 8 Component 2.17 (s, 3H), 2.37 (s, 3H), 3.86 (s, 3H), 3.88 (s, 3H), ?'"H-NMR (400 MHz, 5AM) 4.55(d,J~6,2H), 6.82 (d, J =8, 1H), 6.90-6.95 (m, 2H), 7.17-7.21 (m, 2H), 7.45 (br s, 1H), 7.50 -7.57 (m, 3H).0

N J ad

A

: Compound 69 1 :95 ,2H), 7.16-7.34 (m, 8H), 7.48-7.56 (m, 3H).

MH" = 320 minutes; 7.11 Retention time: (LC/MS 0 1 N 3

Compound 70 \

Ve compound MH" = 352 Retention time: 7,197 min; (LC/MS

0

N N

17-0

N

Compound 71

Composite VY 0.94-1.05 (m, 2H), 1.11-1.31 (m, 3H), 1.52-1.87 (m, ?1H-NMR (400 MHz, CDCI3): § 6H), 2.18 (s, 3H) , 2.35 (s, 3H), 3.25 (t, J = 7, 2H), 7.16-7.21 (m, 2H), 7.22-7.29 (m, 1H), 7.48-7.57 (m, 3H). 2 111 - 312 Detention time: 7.77 minutes; (LC/MS 0 n1 |] A 3 Compound 72

Composite VY 1.50-1.78 (m, 12H), 1.88-1.98 (m, 2H), 2.18 (s, 3H), ?1H-NMR (400 MHz, CDCI3): § 2.34 (s, 3H), 4.12 -4.23 (m, 1H), 7.10-7.20 (m, 3H), 7.48-7.57 (m, 3H). Yo

MH" = 326 min; Y,AA holding time: LC/MS o OH:

N SO

for H

S

Compound 73

— VV — (VY composite 1.65-2.07 (m, 9H), 2.17 (s, 3H), 2.32 (s, 3H), 3.73 (s, 2111-1116 (400 MHz, CDCI3): § 2H), 7.16-7.20 (m, 2H), 7.41 (br s, 1H), 7.49-7.57 (m, 3H).

MH" = 314 minutes; Y,YY Retention time: LC/MS 0

CO

3

Compound 74 o :7 4 Compound 1.56-1.66 (m, 4H), 1.73-1.87 (m, 4H), 2.18 (br s, 6H), 2111-1116 (400 MHz, CDCI3): § 3.65 (t ,J=7,2H),3.91 (t, J =7, 2H), 7.19-7.23 (m, 2H), 7.47-7.56 (m, 3H).

MH" - 297 min; 7.11 Detention time: (LC/MS 0

Na

N

2 fumaric acid

Compound 75 +,10 = (V/V) ©/30 = methanol / dichloromethane) Ry:Ve

— VA — 0

N N

1 1] 1" = 06 cm Compound 76

MH" = 307 4882), AA Retention Time: LC/MS V1 Composite

LC/MS: retention time: 1.88 minutes; MH" = 307. 0 0 CY 1 F for N SA 0 0 Compound 77 Compound 78 Melting Point: range from 119 = 1117 C | Melting Point: range from 134 - 78 C © Example No. : Formulation of Compound No. 1 for Oral Ingestion (PO) to Desired Amount (from 10 to ∼ mg) of Compound No. 1 in Solid Form and Placed in a Glass Tube; Glass Beads are Added and Grind the solid by means of a vortex mill for 2 minutes, and after adding 1 ml of be 3 solution of methylcellulose 711 in water 5 ZY (vol/v) of: Poloxamer 188 (Lutrol F68) 0 ; The compound was suspended by vortex rotation for 10 minutes.The pH was adjusted at V using a few drops of 11N aqueous NaOH.The remaining particles in suspension were resuspended again using an ultrasonic bath. My voice.

4NO for intraperitoneal administration (rip) to the desired amount (0.8 to 11 mg) of compound #1 in solid form placed in a glass tube; Glass granules were added and the solid was ground by means of a vortex mill for 2 minutes. and after adding 1 ml of a solution of methylcellulose ZV in water and 78 mannitol in © water; The boat was suspended by vortex rotation for 10 minutes. The pH was set at 7. Example No.: Pharmacological test results The cannabinoid receptor binding susceptibility data obtained according to the methods preceding cleanin gi are illustrated in the following table. where BMS-1, 13145-11, and 13145-111 are the three ibid 0 imidazole compounds given in International Application 588594/01 (Examples 64, 5, and 16 in that application, respectively). These three specific imidazole derivatives prea contain a moiety

Lk (I H)-imidazole at the - position; From the L-phenylalanine moiety derived from carboxamide as shown in the following diagram. Our invention includes novel (I H)-imidazole derivatives that do not contain such a carboxamide moiety derived from L-phenylalanine but have an affinity for binding to the CB receptor, one hundredfold higher than the prior art compounds mentioned in the examples shown. In international order 088854/11; As it will be clear from the data provided in Table 1. No. a sth “THO SY oo 0 P J M 0 L A ° 8145-11 81/5 8045-1

Table No. (1) 7 | ese eT a Yves

Claims (1)

AY — — hamaba_elements 1 1 - Compounds of the general formula (I) R, 9 N R, (1) Y b R, YF where led ; 0,8 expresses a hydrogen atom or halogen; or a pyr-alkyl group; 0 where the :© - alkyl group may contain 1 to ? A fluorine atom “fluoro atom” or contains 71 hydroxy or amino groups “or Ry expressing a group between - an alkynyl or a Cy group. VY d - Cus “alkenyl group may contain di-alkynyl or b group = alkenyl A over 1 to 'fluoro atom; OR Ry stands for cyclopropyl sl acetyl group 4 or cyano or methylsulfonyl or ethylsulfonyl or methylsulfinyl or ethylsulfinyl trifluoromethylsulfanyl 0 or methylsulfanyl or ethylsulfanyl or foryl group or 11 between groups - heteroalkyl . Ry VY denotes a phenyl group. It may be substituted with 1 or IY * or ; or © from 1" oY substituent groups which may be the same or different; choose from the group consisting of methyl 01, chloros hydroxys ethoxys methoxys propyl s ethyl, 1000 bromo s fluoroy 0 and carbamoyl 3 methylsulfonyl 5 trifluoromethoxy s trifluoromethyl 0 , assay and msm + or Ry expresses a “heteroaryl group where a substitution may occur in Y and a 1b heteroaryl 'VY 0 ?' of the 57 substitution groups; Cua YA bearing The same as the previous inal, provided that Ry is not a group: Z 6-methyl- 2-pyridyl 8 » or Yvasg AY — - 0 0 y denotes a fused carbocyclic ring system that is tricyclic, dicyclic, or monocyclic fully saturated or having one unsaturation site; it contains ; to 01 YY atoms; or Ry denotes a fused heterocyclic system that is tricyclic, YY dicyclic, or monocyclic fully saturated or having one unsaturation site; it contains ; to 01 ocd 3 YE where substitution may occur in the carbocyclic ring system or the heterocyclic ring system Yo with a number ranging from 1 to *#7 substitution groups to choose from methyl or ethyl or amino or hydroxy or 111010 or Ry, 71 expresses a group with the general formula CHp-Rs where Rs expresses a phenyl YA group that has been substituted with 1 or ? or? or; or © of the substitution groups 7 as already defined 4 above; or Rs denoting heteroaryl group or group: : ,2,3,4-tetrahydronaphtyl 0 1 or group 100091; Cua substitution may occur in heteroaryl group 1, 2,3,4-tetrahydronaphtyl group 1, 1 indanyl group, 1, or TTY of the 57 substitution groups as previously defined dle or Rs denotes a carbocyclic ring system fused to a tricyclic, dicyclic or monocyclic ve that is fully saturated or has one unsaturation site; it contains ; to 10 atoms; or Rs TO denotes a heterocyclic fused tricyclic, dicyclic, or monocyclic © system that is fully saturated or has one unsaturation site; it contains ; to 10 atoms; Where a YY substitution may occur in a carbocyclic ring system or a non-FA heterocyclic ring system with a number of from 1 to © substitution groups choosing from methyl Y4 i.e. ethyl or amino or hydroxy or fluoro « or (0 85) expresses a methylsulfonylaminoalkyl group or 1 methylsulfonylalkyl group or an acetamidoalkyl group « "; mi stands for a hydrogen atom an atom or a halogen atom - Mother EV formyl group or of alkylsulfonyl 0 M alkylsulfinyl or p of alkylsulfanyl or benzylsulfanyl or cyano ¢ or Ry denotes a group of Clg = alkyl fo where a substitution may occur in the © - alkyl group with a number ranging from 1 to © Of the £3 substituent groups that coagulate from the group consisting of fluoro, amino § hydroxy, EV ¢, or Ry expressing an alkynyl - Cy, alkenyl - Cy, alkanoyl, or Min group cycloalkyl = ¢A or heterocycloalkyl — Css £9 or heteroalkyl - Cog ; Where optional substitution may occur in these combinations by 1 to ?©. methyl group; or with an ethyl, amino, or hydroxy group ©) or b 1 to “fluoro atoms; Or Ry denotes a phenyl group in which a “©” substitution occurred in a number ranging from 1 to © from oY substitution groups where 7 has the same meaning as the aforementioned ©; or Ry denotes a heteroaryl group where it may A substitution occurs in 1 heteroaryl group 0 or ? or ¥ of substituent groups 7 where 7 has the same meaning as the aforementioned 00 or Rs stands for benzyl dc sane or heteroaryl methyl where the 7 substitution may occur in benzyl group or heteroaryl methyl group b1 or v4 Y from Sle sana ev substitution 7. CA B8 expresses one of two subsets ( ) or ( THEN): 0 0 A ALR Rs N \ Rg 89 0 (i) cycloalkyl = Cig branched or straight or group alkyl Cog denotes Rg group where 0 or alkyl = Cio - cycloalkyl or group 11 dc gamma VY ben - alkyl Cj, - heterocycloalkyl or the bicycloalkyl f group or Yva¢ At — - AY alkyl group Wu Cp - bicycloalkyl group or U tricycloalkyl group - Pr - alkyl 64 or group M tricycloalkyl or tricycloalkyl group — Pr = alkyl or 17 group “alkyl - Cp - heterotricycloalkyl Copp substitutions may occur in these TY groups with from 1 to © of substituent groups choosing from methyl, hydroxy 1A, ethyl, trifluoromethyl, or fluoro ¢ or m denotes a phenyl group or benzyl 14 or naptyl or phenethyl groups which may have a substitution on the aromatic cyclic VY system in them with a number ranging from 1 to ? Of the 7 substitution groups already 11 defined above; Provided yi is that Rg is a 2-methylphenyl group ; Or Rg expresses VY thienyl § pyridyl group . Ry VY stands for 353 hydrogen atom or a straight alkyl Cig group where VE substitution may occur in the straight alkyl Cpe — de sane by 1 to ¥ a fluoro atom ; VO or 8 is an isopropyl group. Rg 1 expresses a Gua ¢ alkyl Cog group in which a hydroxy group or amino VV or B 1 substitution may occur to a Y fluoro atom ; or Rg expressing a YA branched alkyl group or Rn cycloalkyl group or V4 heterocycloalkyl group Cs.g or cycloalkyl Cy 4 = sane - R = alkyl 0 or alkyl Cy, — heterocycloalkyl - Cs. 4c sama or 1 meo bicycloalkyl group or alkyl Cj group, — bicycloalkyl Cs.jp AY or tricycloalkyl lauri group - yr = alkyl or tricycloalkyl nam group or AY group W alkyl - Cp — tricycloalkyl or Af alkyl group Crp - heterotricycloalkyl ; They are groups in which Ao may be substituted by a number of 1 to © substituent groups choosing from methyl, hydroxy, or Ao — - ethyl Al i.e. methyl hydroxy § amino or not trifluoromethyl or fluoro ¢ or Ry expresses a phenyl group that may be substituted by a number of AA _ ranging from 1 to © of the 7 substitution groups as already defined above; or Ry expressing 4 napthyl group i.e. 1,2,3,4-tetrahydronaphtyl 0 or indanyl ¢ where a substitution may occur in a napthyl group or 1,2,34-tetrahydronaphtyl 91 or indanyl b 1 to ¥ of the ¢Y or Rg substituent groups 7 expressing a phenyl-pyr-alkyl group or a diphenyl-yen = alkyl group; AY where in these groups a substitution may occur on the phenyl ring in which it is located by 1 to © of 96 substituent groups oY where 7 has the same meaning as aforementioned; or Rg expressing benzyl group 40 ; where a substitution occurs in a benzyl group b 1 to © of the substitution groups 41 17 or m expresses a heteroaryl group or heteroaryl methyl or methyl naptyl or heteroaryl ethyl dV where a substitution may occur in a group methyl § heteroaryl heteroaryl 4 or methyl napthyl or heteroaryl ethyl b 1 to ¥ of the 44 substitution groups oY where 57 has the same meaning as above; or Rg expressing piperidinyl group 0 or azepanyl or morpholinyl 011 or azabicyclo[3,3.0]octanyl or 4-hydroxypiperidinyl or pyrrolidingl 0" " provided that it is not Rg is 01" 6-methoxy-benzothiazol-2-yl group and [3-chloro-5-(trifluoromethyl)pyrid-2-ylmethyl group ~~ 04 or Rgs Ry - together with the nitrogen atom nitrogen atom) + 0 3 attached to them forming a triple, binary or 0 monocyclic heterocyclic group; non-aromatic or partially aromatic; saturated or unsaturated; It contains 01 to 01 atoms in ddl) in which a substitution may occur in the triple heterocyclic group 08 or Sass monocyclic; non-aromatic or partially aromatic; saturated or unsaturated by the Yvag number - AY = 4 ranges from 1 to © substituent groups choosing from the group consisting of cis alkyl 001, hydroxy, methoxy, cyano, phenyl, trifluoromethyl, or VV atom) halogen atom ¢ 1 or Ry together with the nitrogen atom which adi forms de gana 11" saturated monocyclic heterocyclic; optionally containing a heterocyclic 4 other (choose from ofS ON and have from 0 to +7 atoms per ring; where substitution may occur in the tricyclic, dicyclic, or monocyclic heterocyclic group; non-aromatic or aromatic (La) 11 and saturated or unsaturated with a number of From 1 to © from substitution groups 1 _ which is chosen from the group consisting of alkyl Ci3 i.e. hydroxy i.e. phenyl § amino or benzyl 08 or fluoro; provided that yi is both Ry is together with the nitrogen atom 0 to which a Lo aza-bicyclo[3,2,1]octanyl group is attached substituting a trimethyl YY group. ¢ 111 and its tautomers and N stereoisomers -oxidess stereoisomers terminated 1", as well as salts, hydrates s, and solutes of compounds of the formula (I) mentioned, and their forms 101 "tautomers, stereoisomers, and 8p11-0<10_of them. (1) According to Claim No. (I), compounds of formula -1 b x R, N R, (0) Y R, led Cus YW ; , 8 denotes a 0 halogen atom or a group: © - alkyl ¢ where it may contain © oalkyl - C3 group on 1 to Y fluoro atom ; or on the hydroxy group = L , camino or Ry expressing an alkynyl group = Cj or a yin group = an alkenyl « V where the group of a do = alkynyl group or a b - alkenyl group may contain 1 A to? a fluoro atom ¢ or ud R; of an acetyl, cyclopropyl, cyano 4, methylsulfonyl, ethylsulfonyl, methylsulfinyl, ethylsulfinyl trifluoromethylsulfanyl 0 or methylsulfanyl group or ethylsulfanyl 0 formyl group OR 11 sale group = heteroalkyl ; WE R35 and B carry the same meanings previously mentioned in NY Claim Claim No. (1). FY) compounds of formula (1) according to claim No. -1 R, Bud Z RNR, 0 : R, W where: ¢ - and 8 expresses a hydrogen atom or a halogen; or formyl group ee or methylsulfonyl or methylsulfinyl 0 ethylsulfonyl or ethylsulfinyl trifluoromethylsulfanyl 1 or ethylsulfanyl 0 methylsulfanyl or cyano V ¢ or Ry expresses an alkyl - Cig group as the group may contain oalkyl = Cre A over 1 to ? fluoro atoms « or hydroxy group i.e. amino » or Ry 9 expresses a mon-alkynyl group or an alkenyl - Cay parent alkanoyl or 0 yon = cycloalkyl or heterocycloalkyl - Cs.g or from - heteroalkyl ; Cua yy may selectively substitute in these groups with a 1 to ¥ methyl group ; or with an ethyl VY group or an amino or hydroxy ¢ or b 1 to ? fluoro atoms; 0 VY and 8 denote a phenyl group that has been substituted by 1 to © groups AA = 4 Substitute oY where 7 has the same meaning as above; or Ry expressing the heteroaryl group Vo where substitution may occur in 1 heteroaryl de same or Y or * from the oY NT substitution groups where 7 has the same meaning as above; Or Ry expresses a benzyl group i.e. methyl Cua ¢ heteroaryl VV substitution may occur in benzyl dc gana or heteroaryl methyl group 08b1 or YAY from the substitution groups GY 0 - y expresses a subgroup of the form (i) 0 if N Rs Y. »> (ii) vy where vy - y represents an atom hydrogen atom or straight alkyl Crs group or YY isopropyl group ; Ry™ 4 expresses an alkyl Cog group; Where it may have a hydroxy group substitution, amino Yo, or b 1 to ? a fluoro atom; or Rg expressing an alkyl group - branched or cycloalkyl group Cig or heterocycloalkyl group Cs.g or Cig 4c sana cycloalkyl + — yz = alkyl or alkyl group C2 - heterocycloalkyl - Cs; or YA a bicycloalkyl group or a mo-bicycloalkyl group — ir alkyl or ic gana v4 or alkyl - Cy, — tricycloalkyl or a tricycloalkyl mon group or a group mm0 alkyl - Ci; - tricycloalkyl + or 01 alkyl groups Crp - heterotricycloalkyl ¢ which are groups in which a + substitution may occur with a number ranging from 1 to © of substituent groups that choose from methyl i.e. hydroxy or ethyl vv or methyl hydroxy 0 amino or trifluoromethyl or fluoro v¢ ¢ or Rg expresses a phenyl group. It may have 1 to 5 Yva¢ substitutions. - do - © from the 7 substitution groups as defined above; or Ry denotes a napthyl group or o—f FY 1 ¥X tetrahydro napthyl or indanyl where .TY substitution may occur in these groups by 1 to ? of replacement groups 7; Or Rg denotes a phenyl - TA dz - alkyl group or an alkyl - © - diphenyl group where a substitution may occur in these groups on the phenyl ring in which they are by 1 to © from 5 replacement sets; where 0 7 has the same meaning as above; or Rg expressing a benzyl group; where 1 substitution occurs; or Rg stands for heteroaryl group ¢Y or heteroaryl methyl ¢Y or heteroaryl ethyl where a substitution may occur in heteroaryl methyl group § heteroaryl 4 or heteroaryl ethyl by 1 to ¥ of groups fo substituting oY where 7 has the same meaning as aforementioned; or Rg expressing piperidinyl group £1 or azepanyl meaning morpholinyl group azabicyclo[3,3.0]octanyl meaning 4-hydroxypiperidinyl 1 or pyrrolidiny]l “provided that it is not Rg is a group: p 6-methoxy-benzothiazol-2-yl group nor a [3- chloro-5-(trifluoromethyl)pyrid-2- yllmethyl £4 0 or p-y - together with an atom The nitrogen atom to which the US is attached is a group 0) tricyclic, dicyclic, or monocyclic heterocyclic; Unsaturated Ake or aromatic Lise OY, saturated or unsaturated; It contains 7 to 10 atoms per ring; Where the ov substitution may occur in the heterocyclic group with one or two substituent groups of choosing from hydroxy § alkyl i.e. trifluoromethyl phenyl or benzyl group 5 or di-methyl phenyl group or a halogen atom ¢ o% or Rss R; together with a nitrogen atom that bonds (lege) they form a saturated monocyclic heterocyclic OV group; optionally containing a heterocyclic atom monolithic - 8.0 other 0A (selected from ofS ON and have © to + atoms in the ring, where substitution of the heterocyclic group sod may occur with a number of 1 to ? substitution groups 0 chosen from the constituent group From © alkyl or hydroxy or 1 to Y a fluorine atom fluoro atom 7 + 1 provided that both Ba Rss together with the nitrogen atom 7 are bonded to a group aza-bicyclo[3.2.1]octanyl has a trimethyl group substituted; Ry Ry 17 have the same meanings as aforementioned in Claim No. (?). PY); = compounds of formula (1) according to Claim No. 1 R, N XX R; 1 and (1) Y R; : where oy ; , 8 expresses a 0 halogen atom or a © - Cua ¢ alkyl group 6 may contain a C3 - halogen group on 1 to ? A fluoro atom + or on a 1 hydroxy group or Ry expressing a B = alkynyl group, an inter-alkenyl group, an acetyl 0 group, a cyano 0 cyclopropyl group, or a methylsulfonyl group Or methylsulfinyl or Bm methylsulfanyl or a group between - heteroalkyl . XR 4 of a phenyl group may be substituted with 1 or 7 or “ or ; or © of 0 substitution groups 7 which may be the same or different; and choose from the group consisting of 1-hydroxy ethoxys methoxy propyls ethyl s methyl and trifluoromethoxy trifluoromethyl s fluoro bromo and iodo chloro 01 heteroaryl express the Ry group; or cyano sy phenyl ys carbamoyls methylsulfonyl s yy 91 _ - 4 monocyclic; where a substitution in heteroaryl may occur with 1, ", or ¥ of the Vo groups substituting 7 where 7 has the same meaning as above; provided that Ry is not a methyl - 7 - ?- pyridyl group + or Ry, VY denotes a carboxylic ring system fused to a tricyclic, VA, polycyclic, or monocyclic fully saturated or having 1 unsaturation site; containing 4 to 10 atoms; or Rp denotes a fused heterocyclic system that is tricyclic, dicyclic, or monocyclic fully saturated or has 1 unsaturation site; contains 4 to 10 YY atoms; Cus substitution may occur in the carboxycyclic cyclic system carbocyclic ring system vy or heterocyclic ring system with number from 1 to © YY substituent groups choosing from ethyl 0 methyl, amino, hydroxy or fluoro + or; R, expresses a group having the general formula CHp-Rs, where Rs expresses a phenyl Yo group that has been substituted with 1 or ? or “ or ; or © of the 5 substitution groups as previously defined Y1 above; or Rs denotes heteroaryl group or OY group YO);- tetrahydr napthyl YY or 100071 + Cua group. Substitution may occur in heteroaryl group or YA ,2,3,4-tetrahydronaphtyl group 1 or 1 indanyl group or ? or * from the YA substitution sets Y as defined above; or Ry denotes a carbocyclic ring system Ye that is fused tricyclic, dicyclic, or monocyclic fully saturated or has 1 unsaturation canal containing ; to 10 atoms; or Rs denotes a non-YY-coupled homocyclic tricyclic, dicyclic, or monocyclic system that is fully saturated or has a single unsaturating FY locus; it contains ; to 10 atoms; where an optionally substitution may occur in the YE carbocyclic ring system or the heterocyclic ring_system Yo ank/©160._with a number ranging from 1 to ? Substituting groups choosing from 3-methyl, ethyl, amino, hydroxy or fluoro ¢ seed ay _ - umd Ry YTV for a hydrogen atom or a log atom + halogen or a methylsulfanyl group or a cyano group; Or Ry denotes an alkyl group = Cj ¢ YQ where the Cr-abola group may contain a number from 1 to ? fluoro atom 0, hydroxy group, or amino group; or b expresses dc sans yen - alkynyl or “alkenyl - Cog 1 where optional substitution may occur in these groups with 1 to SAY fluoro ¢Y ¢ Ry EY expresses a group A subset of the form H(i) 0 the R, £ ¢ > 1 (ii) £0 where: R; 5 denotes a hydrogen atom or a straight alkyl Cig group; Ry EV expresses an “alkyl Cop” group in which a hydroxy group or amino £A or B 1 substitution may occur to ? a fluoro atom; or Rg denotes a 0 alkyl group £4 branched or a right cycloalkyl group or a heterocycloalkyl min group or a Cig alkyl group - Cp, - cycloalkyl 0 or a B group = alkyl C1 - heterocycloalkyl or © wu bicycloalkyl group or 4c sane mon alkyl Cy, — bicycloalkyl or © tricycloalkyl medy group - ybrn = alkyl or wu tricycloalkyl group or OY w tricycloalkyl group - rn = alkyl or a group of 0 heterotricycloalkyl - “alkyl ©, OF” groups in which a substitution may occur with a number of 1 to © substituent groups choosing from methyl i.e. hydroxy i.e. ethyl or amino i.e. methyl hydroxy trifluoromethyl 4©% or fluoro; or Ry expresses a phenyl group with which a substitution may occur © ov has a number ranging from 1 to © of the 7 substitution groups as defined above; OR and 18 OA expresses a napthyl group ie 2,3,4-tetrahydronaphtyl 1 or 100A 091 ; Cua substitution 4 in a napthyl group may occur that 2,3,4-tetrahydronaphtyl 1 or indanyl b 1 to * of 0 substitution groups ¢Y or Ry express an alkyl group = ©, = phenyl or Cry - diphenyl group 1 - nor; Cua substitution may occur in these groups on the phenyl ring 7 in them by 1 to © of the 57 substitution groups; Where 7 bears the same meaning as the aforementioned 7; or Rg denotes Cua “benzyl group” Substitution occurs in benzyl group by 1 4 to 0 of the 77 substituent groups; Or Rg expresses heteroaryl group i.e. methyl heteroaryl To or “heteroaryl ethyl” where substitution may occur in heteroaryl group or heteroaryl methyl 1 or YY — heteroaryl ethyl TY of the substituent groups 7; where 7 has the same meaning as the aforementioned TA; or Ry expressing a piperidinyl group or azepanyl or morpholinyl or azabicyclo[3.3.0Joctanyl 4 or 4-hydroxypiperidinyl or pyrrolidingl | 1 “provided that Rg is neither 6-methoxy-benzothiazol-2-yl group nor 1 [3-chloro-5-(trifluoromethyl)pyrid-2-ylJmethyl” 1 group > - Compounds of general formula (1) according to Claim No. (4): Ma a A R, (1) Y b R, : in it dus YW where «alkyl -©, or a + halogen atom group expressing an 8, hydroxy halogen atom may contain a «fluoro atom to ? Atom fluorine 1 on oalkyl - ©: © group 1 1 or 8 expresses the cyano group i.e. methylsulfanyl ; Ry VY denotes a carbocyclic ring system that is fully saturated + monocyclic or has only one unsaturation site; contains © to 1 atoms; where 4 substitutions may occur with a number of 1 to © substitution groups choosing from methyl, ethyl, hydroxy § amino 0, fluoro ¢ or Rp expressing a phenyl group that has been substituted b 1 11 or ? or JF; or © from the 7 substitution groups; which may be similar or different; and 0" is chosen from the group consisting of | methyl , propyl 5 ethyl , methoxy , ethoxy VY , hydroxy , chloro , iodo , bromo and fluoro , trifluoromethyl , trifluoromethoxy 4 , methylsulfonyl , carbamoyl Yo , phenyl , cyano ; VY may express a hydrogen atom or a halogen atom + or 11 A methylsulfanyl group or a cyano group; or Ry expresses an alkyl group = Ci; VA where an alkyl - Cry group may contain a number ranging from 1 to ¥ a fluoro atom atom 4 or hydroxy 4c sane or amino ¢ 70 s expresses a subgroup of formula (if) 0 i N >” Rs 71 0 YY where in : pai 87 YY for a hydrogen atom or methyl dc sane VE 8. denotes the “alkyl Co” group in which substitution may occur by 1 to ? fluoro atom Yo; Or Rg expresses a branched alkyl group or a cycloalkyl yin group k or a heterocycloalkyl yl group or Ci - heterocycloalkyl - pol dc gana or alkyl - bur - cycloalkyl yen group YV alkyl Ci, = bicycloalkyl or wt bicycloalkyl group Cs.jo or alkyl YA group or tricycloalkyl group or 0 alkyl - yen - tricycloalkyl group or diacytic group Ci. - heterotricycloalkyl or an alkyl group - Cy, —tricycloalkyl group mm © to © from 1 groups, which may have substitutions with a number ranging from “alkyl 1 methyl 2 methyl hydroxy” i.e. amino i.e. ethyl Any hydroxy, any methyl substitution that chooses from FY, may have a phenyl substitution that expresses the Rg group; or fluoro or trifluoromethyl or 0 as defined above; or M18 expresses Y to © from 1 substituent groups with a number ranging from TE where a ¢indanyl or 1,2,3,4-tetrahydronaphtyl substitution may occur for the Yo group to ? of 1 — indanyl or 1,2,3,4-tetrahydronaphtyl or napthyl in Mm group or alkyl - C5 - phenyl dc gana expressing Rg or ¢Y substituent groups TV TA alkyl -©, — diphenyl group where substitution in these groups may occur on the YA phenyl ring in which it is in 1 to © of the oF substitution groups where 7 has the same meaning as 0 aforementioned; or Ry expressing a benzyl group; Cus substitution occurs in group 1 — benzyl 61 to © from Cle gana substitution 7; or Ry stands for heteroaryl group or heteroaryl methyl ¢Y or heteroaryl ethyl where 8 substitution occurs in heteroaryl ¢Y group i.e. heteroaryl methyl or heteroaryl ethyl by 1 to ¥ of combinations oY Jain] £6 where 7 has the same meaning as above; Given V1, Ry is the group -6-methoxy-benzothiazol-2-yl £0 and the group: “[3-chloro-5-(trifluoromethyl)pyrid-2-yljmethyl | ¢1 1 + - Compounds of formula (1) according to Claim No. (E): M I] A N 8 0 B 3 Y R, : where Y may contain Cua alkyl -©. or combination + halogen atom; 0 6-7 represents a halogen atom that represents a group of Ry or ¢ fluoro atom to ? fluorine atom 1 on alkyl -©: © group « methylsulfanyl or cyano 1 monocyclic fully saturated carbocyclic ring system expressing a carboxylic ring system R; VY 1 may be substituted with phenyl ic gana It expresses R, 64 and contains . atoms' or A substitution groups 7; which may be similar or different; It is selected ge FS Y or 9, ethoxy, methoxy, propyl, ethyl and methyl from the group consisting of Y., trifluoromethyl 5 fluoro and bromo iodo, chloro 5 hydroxy 11 ¢ cyano, phenyl, carbamoyl, methylsulfonyl s trifluoromethoxy 01, halogen atom or a hydrogen atom expressing a VV ¢ alkyl hydrogen atom - bar 4c sana stands for Ry; or cyano or a methylsulfanyl group 4 fluoro group to 1 fluorine atom has an alkyl number - where the m Vo ¢” group may contain atom 1 (i) for a subgroup of the formula Ry VY 0 AR RgVA 0 4 where it contains: ¢ methyl hydrogen atom expresses a hydrogen atom, 87 00 Rg YY denotes a Cus «alkyl Cog group that may be substituted with 1 to * fluoro atom YY ¢ or Rg denotes a branched alkyl Crip or a cycloalkyl ion group YY or ic sana yun heterocycloalkyl or cycloalkyl group Cig = yen = alkyl or ; heterocycloalkyl group - Cs; - ben alkyl group or mi bicycloalkyl group or yo group and min bicycloalkyl - pyr alkyl 0 mo tricycloalkyl group - rn = alkyl 7 or tricycloalkyl tumor group Or group and tricycloalkyl - Pr - alkyl VY or group YA range of heterotricycloalkyl - yer alkyl + groups in which a substitution may occur with a number of YA ranging from 1 to © of substituent groups choosing from methyl i.e. hydroxy or ethyl 0 or amino or methyl hydroxy or trifluoromethyl or fluoro ¢ or Rg expresses 1 phenyl group that may be substituted with from 1 to © of LS 7 © substituent groups" previously defined above; or Lud Ry for napthyl group or -2,3,4,1 tetrahydronaphtyl YY or 100071 ; Cus substitution may occur in napthyl group or -2,3,4,1 tetrahydronaphtyl 0 or indanyl b 1 to ¥ substituent groups ¢Y or Rg expressing YO an alkyl - C13 - phenyl group or an alkyl group = ©, - diphenyl ; where © may substitution occur in these groups on the phenyl ring in which they are in 1 to © from VV substitution groups 77 where 7 has the same meaning as aforementioned; or Ry denotes a benzyl group YA where substitution occurs in benzyl group B 1 to © of the CY substituent ve groups Yvas 4A — - 1 7 - a compound of the general formula (XIV) 0 “for R, R, Re Y (XIV) gp where: ; 8, expresses a halogen atom 0 halogen atom or a group: © - “alkyl”, where M may contain a group: © - analta to 1 to “a fluoro atom; or on a 1-hydroxy or amino group; or R; denotes a u = alkynyl group or an - alkenyl group ; + where an alkynyl - Cs group or a :© - alkenyl group may contain 1 to SAV bm fluoro atom sb ¢ or Ry expressing a cyclopropyl 0 acetyl or cyano group or methylsulfonyl q or ethylsulfonyl or methylsulfinyl or ethylsulfinyl trifluoromethylsulfanyl or methylsulfanyl or ethylsulfanyl or a formyl group or yy a B group - heteroalkyl + Ry yy expresses phenyl group 8 is substituted with 1 or 1 or or ; or © from yp Substitution groups HY may be the same or different; and choose from the group consisting of propyl ethyl s methyl +, chloros hydroxy ethoxy s methoxy, 1000 bromo methylsulfonyl trifluoromethoxy s trifluoromethyl fluoros yo and carbamoyl a cyanos phenyls » or 82 expressing the heteroaryl group + where a substitution may occur in 1 heteroaryl yy, or 1 YJ of the oY substitution groups where ¥ has the same meaning as before; Provided that R, is not a 6-methyl- 2-pyridyl group » or R, 15 expresses a fused three-ring carbocyclic ring system or - aq_ SEY.cyclic or monocyclic is fully saturated or has only one unsaturation position; it contains ; 1 to 0 atoms; or Ry denotes a fused heterocyclic system that is tricyclic, dicyclic (lila) vy, or monocyclic fully saturated or having a single unsaturation site; Contains 4 to 01 YY atoms 0 where substitution may occur in the carbocyclic ring system ve or the heterocyclic ring system with a number ranging from 1 to ©Yo groups Substitution choose from methyl i.e. ethyl or amino i.e. hydroxy or fluoro + or R, Y1 expresses a group with the general formula CHp-Rs where Rs expresses a phenyl group YY has been replaced by 1 or ? or? or; or © of the Y substitution groups as already defined 8 above; or Rs denotes heteroaryl group or ,2,3,4-tetrahydronaphtyl group 1 or 4 group 0«1l00; where substitution may occur in heteroaryl de sana or group -2,3,4,1 tetrahydronaphtyl 00 or indanyl ic sane by 1 or ? or ¥ of the substitution sets a as 1 defined above; or Ry denotes a carbocyclic ring system TY fused tricyclic, dicyclic, or monocyclic that is fully saturated or has one unsaturation position; it contains ; to 10 atoms; or Rs denotes a conjugated heterocyclic system ve tricyclic, dicyclic, or monocyclic that is fully saturated or has a single To unsaturation position; it contains ; to 10 atoms; Where a substitution may occur in the carbocyclic ring system ~~ Y1 or the heterocyclic ring system by a number of YY ranging from 1 to © substitution groups choosing from methyl, ethyl, or amino or hydroxy YA or 1000 or 4 8 represents the methylsulfonylaminoalkyl group or “acetamidoalkyl group or methylsulfonylalkyl group 0 -phenyl, 4-methylphenyl or 4-methoxyphenyl for the Ry group, provided that it does not express 1; Ry 7 stands for 5.0 hydrogen atom or 0 halogen atom or 1011 or alkylsulfinyl Which of the alkylsulfonyl do I see from formyl?; group expresses the group Ry; or cyano sl benzylsulfanyl sf alkylsulfanyl from ¢¢ to 1 with a number ranging from alkyl = Cg where a substitution may occur in the alkyl -© £0 , hydroxy or fluoro substituent groups that choose from the group consisting of ©£1 alkanoyl Cj or alkenyl - or mo-alkynyl - Cig expressing the Ry group ; or amino 1 ; where may heteroalkyl - or min heterocycloalkyl - Cs. or cycloalkyl - Cj or EA; Or by a group of methyl de gana ¥ to 1 4? An optional substitution occurs in these groups with B representing the Ry group ; or fluoro SAY to 1; or b hydroxy or amino or ethyl©. Y where oY to © of the substitution groups 1 substitution occurred with a number ranging from phenyl ©) Cus heteroaryl may occur expressing a group Ry with the same meaning as above; or ©" where Y or 0 ¥ of the substituent groups 1 b heteroaryl substitution in the oy group « heteroaryl methyl sl benzyl expresses a Ry group with the same meaning as above; or of " and 1 a b heteroaryl methyl or benzyl dc sess group where substitution may occur in 00 Y or “ of 0% substituent groups or hydroxy group or alkyl group - or ber + chloro group crossing for an atom 7 ov : or -0- or -1 -©- or -0 -© ; Or 2 expresses a group of Na or -0- on “N-methoxy-N-methyl-amino cq Ri 5 Rp and Ry as these compounds are useful in the synthesis of compounds of formula (1) where they have 0 0 Have the same meanings mentioned in Claim No. (?) 711 A pharmaceutical composition containing, in addition to a pharmaceutically acceptable carrier and/or at least one pharmaceutically acceptable additive - + 1, a pharmaceutically active quantity of one compound on Y + active ingredient to (1); as active ingredient (1) at least according to the claims of © -10110- is characterized by (A) a method for preparing the pharmaceutical compositions mentioned in Claim No. 9 - 1 to (1) in an appropriate formula (1) “At least one compound shall be formulated in accordance with the claims of. For ingestion to (6); or one of its salts; for use as (1) a compound according to any of the claims from 1-01. Preparation of a pharmaceutical composition - 11 1 disorders CB, “all for the treatment of disorders in which the neural transmission of a Y-like receptor contributes. involving cannabinoid CB, receptor neurotransmission ~~ ¥; where it is distinguished that the disorders mentioned (11) of protection No. Wh use - 117 1; or those that can be cured by dealing with those CB, contribute to cannabinoid receptors all and immune system disorders receptors are immune system disorders Y and sclerosis Huntington's disease And Huntington's disease, inflammatory disorders, including cancer, cancer allergies, and multiple sclerosis © 0 neuropathic pain 1