New Alpha2 Adrenoceptor Agonists

TECHNICAL FIELD The present invention relates to pharmacologically active isochroman and isothiochroman derivatives, or pharmaceutically acceptable salts and esters thereof, as well as to pharmaceutical compositions comprising them and to their use as alpha2 adrenoceptor agonists, especially as alpha2A agonists. BACKGROUND OF THE INVENTION The alpha2-adrenoreceptors (a2) are G protein-coupled cell membrane receptors widely distributed in humans and they are sub-classified into three subtypes in human; alpha2A, alpha2B and alpha2C (Bylund et al, Mo/. Pharmacol., 1992, 42, 1-5). Alpha2 adrenoreceptors have a multiplicity of biological functions and compounds effecting to these receptors are attractive targets on various diseases (Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12th edition, 2011, chapter 12; Brede et al Biol. Cell 2004, 96, 343-348). Indeed, many alpha2 active compounds have been prepared (Gentili et al, Curr. Top Med. Chem., 2007, 7, 163-186) and tested in clinical settings (Crassous et al, C rr. Top Med. Chem., 2007, 7, 187-194). For example, partial alpha2A agonist clonidine is used as a blood-pressure lowering agent and non-alpha2 subtype nonselective full agonist dexmedetomidine is used as a sedative in the intensive care units. US Patent no. 3,438,995 discloses some isochroman and isothiochroman derivatives and suggests them to be useful as rubber accelerators, anti-oxidants, corrosion inhibitors, central nervous system (CNS) depressants and anti-inflammatories. WO 2007/085558 discloses a variety of imidazole derivatives useful as TAAR ligands for the treatment of variety of disorders, including various CNS disorders. SUMMARY OF THE INVENTION An object of the present invention is to provide novel compounds exhibiting agonistic activities on adrenenergic alpha-receptors, especially on alpha2A receptor. These compounds can be used for treatment of disorders, conditions or diseases like delirium (for example hyperactive delirium), insomnia, ADHD, benzodiazepine (or alcohol or opioid or tobacco) withdrawal, premature ejaculation, hypertension, tachycardia, restless leg syndrome, muscular spasticity, hot flashes, anxiety, post traumatic stress disorder, pain, chronic pelvic pain syndrome, and breakthrough cancer pain, and other possible diseases treatable with adrenergic alpha2 agonists, especially with alpha2A agonists. Accordingly, the present invention provides further compounds to be used as cooperative sedative or analgesic agent in the treatment of mammals. Furthermore, pharmaceutical compositions comprising the present compounds are provided. The compounds of the present invention are orally active, brain penetrating, selective alpha2A agonists. They have an improved alpha2A activity and/or alpha2A agonistig selectivity against other alpha receptors and/or enhanced potency, as well as improved metabolism in liver hepatocytes in vitro, all together giving moderate in vivo duration of action. Apart from the foregoing pharmacological effects, the compounds of the present invention have less side-effects due to diminutive CYP interactions. The foregoing as well as other features and advantages of the present teachings will be more fully understood from the following description and claims. DETAILED DESCRIPTION OF THE INVENTION The present invention relates to novel isochroman and isothiochroman derivatives having the general formula I, wherein X is O or S; R is hydroxy, halogen, (C]-C )alkyl, halo(Ci-C 6)alkyl, (C -C6)alkenyl, (C2-C6)alkynyl, cyclo(C 3-C )alkyl, (Ci-C 6)alkoxy, halo(C|-C 6)alkoxy, hydroxy(Ci -C )alkyl, cyano, (Ci- C6)alkoxy(C i-C6)alkyl, (C, -C )alkoxy(C ,-C )alkoxy(C C6)alkyl, hydroxy(C ,-C )alkoxy, hydroxy(Ci-C 6)alkoxy (Ci -C )alkyl, hydroxy(C -C6)alkenyl, (C2-C6)alkenyloxy(C 2- C6)alkenyl, halo(C C6)alkoxy(Ci-C )alkyl, halo(C C )alkoxy-halo (Ci -C6)alkyl, (C,- C )alkoxy-halo(C C6)alkoxy, carboxy, (Ci-C 6)alkyl-(C=0)-, (C C )alkoxy-(C=0)-, (QC )alkyl-(C=0)-0-, halo(Ci-C )alkyl-(C=0)-, halo(C,-C 6)alkoxy-(C=0)-, (R ) N-, (R6)2N- ( - a kyl, (R6) N-(C=0)-, R -(C=0)-N(R )-(C=0)-, R6-(0=S=0)-N(R 6)-(C=0)-, R - (C=0)-N(R )-(0=S=OK R6-(0=S=0)-N(R 6)-(0=S=0)- , (R6)2N-N-, (R )N=N-, (R ) N-0- (R )0-N(R 6)-, (C,-C )alkyl-S-, (C2-C )alkeny-S-(C 2-C6)alkenyl, hydroxy(C,-C )alkyl-S-, hydroxy(C -C6)alkyl-S-(C ,-C )alkyl, (C -C )alkoxy(C ,-C6)alkyl^(C ,-C6)alkyl, halo(C ,- C )'alkyl-S-, halo(C,-C )alkyl-S-(C,-C 6)alkyl, haloCQ-C^alkyl-S-haloCQ-C^alkyl, R - (0=S)-, (R6)2N-(0=S)-, R -(0=S=0)-, (R6)2N-(0=S=0)-, phenyl, phenyl-O-, heteroaryl, heteroaryl-O-, phenyl-N(R 6)-, heter0aryl-N(R 6)-, or heteroaryl(C i-C )alkyl; R2 is H, hydroxy, oxo, fluoro, (Ci C6)alkyl, haio(Ci-C )alkyl, (C2-C6)alkenyl, (C2- C )alkynyl, cyclo(C -C6)alkyl, (CV-C )alkoxy, halo(Ci-C )alkoxy, hydroxy(C i-C6)alkyl, cyano, (Ci-C )alkoxy(C ,-C )alkyl, (Ci -C )alkoxy(C 1-C6)alkoxy(Ci-C )alkyl, hydroxy(C ' C )alkoxy, hydroxy(Ci-C )alkoxy(C l-C )alkyl, hydroxy(C 2-C )alkenyl, (C2- C6)alkenyloxy(C 2-C )alkenyl, halo(Ci-C 6)alkoxy(Ci-C )alkyl, halo(C,-C )alkoxy-halo(Ci- C )alkyl, (C -C6)alkoxy-halo(CrC 6)alkoxy, carboxy, (C i-C6)alkyl-(C=0)-, (C C6)alkoxy- (C=0)- , (Ci -C6)alkyl-(C=0)-0-, halo(C,-C 6)alkyl-(C=0)-, halo(C C )alkoxy-(C=0)-, (R )2N-, (R6)2N-(C,-C )alkyl, (R6) N-(C=0)-, R6-(C=0)-N(R )-(C=0)-, R6-(0=S=0)- N(R6)-(C=0)-, R6-(C=0)-N(R )-(0=S=0)-, R6-(0=S=0)-N(R 6)-(0=S=0)-, (R )2N-N-, (R6)N=N-, (R6) N-0-, (R6)0=N-, ( - alkyl-S-, (C -C6)alkeny-S-(C 2-C6)alkenyl, hydroxy(Ci-C 6)alkyl-S-, hydroxy(Ci-C 6)alkyl-S-(C,-C )alkyl, (C i-C6)alkoxy(Ci-C 6)alkyl-S (Ci-C 6)alkyl, halo(C,-C 6)alkyl-S-, halo(C 1-C6)alkyl-S-(C,-C 6)alkyl, halo(C,-C 6)alkyl-Shalo( C,-C 6)alkyl, R6-(0=S)-, (R6)2N-(0=S)-, R6-(0=S=0)-, (R )2N-(0=S=0)-, phenyl, phenyl-O-, heteroaryl, heteroaryl-O, phenyl-N(R 6)-, heteroaryl-N(R 6)-, or heteroaryl(Ci- C6)alkyl; R3 is H, (C i-C )alkyl, halo(Ci-C 6)alkyl, (Q-C 6)alkoxy, halo(C -C6)alkoxy, hydroxy(Ci- C6)alkyl, (C C )alkoxy(Ci-C 6)alkyl, or cyclo(C 3-C6)alkyl; 4 is H, hydroxy, halogen, (C i-C2)alkyl, or halo(C i-C2)alkyl; R5 is H, hydroxy, halogen, (Ci-C 6)alkyl, halo(Ci-C 2)alkyl, cyclo(C3-C )alkyl, (Ci-C )alkoxy, halo(Ci-C )alkoxy, hydroxy(Ci-C )alkyl, phenyl, or heteroaryl; and R6 is, independently at each occurrence, H, (Ci-C )alkyl, (Ci-C )alkoxy(Ci-C )alkyl hydroxy(Ci-C 6)alkyl, halo(C1-C )alkyl, or R and R form, together with the atoms they are attached to, a condensed 4, 5, 6, or 7 membered saturated or unsaturated carbocyclic ring or a condensed 4, 5, 6, or 7 membered saturated or unsaturated heterocyclic ring containing 1 or 2 heteroatom(s) selected from N, O and S, wherein said carbocyclic or heterocyclic ring is unsubstituted or substituted with 1 or 2 substituent(s) each independently being hydroxy, oxo, halogen, (Ci-C )alkyl, hydroxy(Ci-C )alkyl, or halo(Ci-C6)alkyl-; or and R form, together with the carbon ring atoms to which they are attached, a condensed 4 , 5, 6, or 7 membered saturated or unsaturated carbocyclic ring or a condensed 4; 5, 6, or 7 membered saturated or unsaturated heterocyclic ring containing 1 or 2 heteroatom(s) selected from N, O and S, wherein said carbocyclic or heterocyclic ring is unsubstituted or substituted with 1 or 2 substituent(s) each independently being hydroxy, oxo, halogen, (C i-C 6)alkyl, (Cj-C6)alkoxy(C]-C )alkyl, hydroxy(C[-C6)alkyl, or halo(Cr a kyl; or R and R3 form, together with the carbon ring atoms to which they are attached, a condensed 4, 5, 6, or 7 membered saturated or unsaturated carbocyclic ring or a condensed 4, 5, 6, or 7 membered saturated or unsaturated heterocyclic ring containing 1 or heteroatom(s) selected from N, O and S, wherein said carbocyclic or heterocyclic ring is unsubstituted or substituted with 1 or 2 substituent(s) each independently being hydroxy, oxo, halogen, (Ci-C )alkyl, (C)-C6)alkoxy(C i-C )alkyl, hydroxy(C]-C6)alkyl, or halo(Cr alkyl; or a pharmaceutically acceptable salt or ester thereof. In a possible subgroup of the compounds of formula I, Ri is hydroxy, halogen, (Ci -C )alkyl, halo(Ci-C )alkyl, (C2-C )alkenyl, (C2-C6)alkynyl, cyclo(C3-C 6)alkyl, (Ci-C )alkoxy, halo(C]-C6)alkoxy, hydroxy(Ci-C 6)alkyl, cyano, (Ci- C2)alkoxy(Ci -C )alkyl, hydroxy(C1-C2)alkoxy, halo(C|-C 2)alkoxy(C C )alkyl, halo(C C2)alkoxy-halo (C]-C2)alkyl, (Ci-C 2)alkoxy-halo (C C2)alkoxy, carboxy, (Ci-C 3)alkyl- (C=0)-, (C,-C 3)alkoxy-(C=0)-, halo(Ci-C3)alkyl-(C=0)-, halo(C C3)alkoxy-(C=0)-, (R6)2N-(C,-C 2)alkyl, (R6)2N-(C=0)-, (C,-C 6)alkyl-S-, R6-(0=S)-, R6-(0=S=0)-, (R6)2N- (0=S=0)-, phenyl, phenyl-O-, heteroaryl, heteroaryl-O-, or heteroaryl (C C2)alkyl; R is H, hydroxy, oxo, fluoro, (Ci-C )alkyl, halo(Ci-C 6)alkyl, cyclo(C3-C6)alkyl, ( - C6)alkoxy, halo(Ci-C )alkoxy, or cyano; R3 is H, (C C6)alkyl, halo(C -C6)alkyl, ( - alkoxy, hydroxy(CrC )alkyl, (QC )alkoxy(Ci-C )alkyl, or cyclo(C3-C )alkyl; R4 is H, fluoro, (Ci-C )alkyl, or halo(C C2)alkyl; R5 is H, hydroxy, halogen, (Ci-C )alkyl, halo(Ci-C )alkyl, cyclo(C3-C )alkyl, (Ci-C )alkoxy, halo(Ci-C )alkoxy, phenyl, or heteroaryl; and R6 is, independently at each occurrence, H, (Ci-C )alkyl, or R and R form, together with the atoms they are attached to, a condensed 5, 6 or 7 membered saturated or unsaturated carbocyclic ring or a condensed 5, 6 or 7 membered saturated or unsaturated heterocyclic ring containing 1 or 2 heteroatom(s) selected from N, O and S, wherein said carbocyclic or heterocyclic ring is unsubstituted or substituted with 1 or 2 substituent(s) each independently being hydroxy, oxo, halogen, (C|-C 2)alkyl, or halo(C1-C )alkyl-; or Ri and R2 form, together with the carbon ring atoms to which they are attached, a condensed 5, 6 or 7 membered saturated or unsaturated carbocyclic ring or a condensed 5, 6 or 7 membered saturated or unsaturated heterocyclic ring containing 1 or 2 heteroatom(s) selected from N, O and S, wherein said carbocyclic or heterocyclic ring is unsubstituted or substituted with 1 or 2 substituent(s) each independently being hydroxy, oxo, halogen, (Ci- C )alkyl, (Ci-C 2)alkoxy, hydroxy(C C )alkyl, or halo(Ci-C )alkyl. In a further possible subgroup of the compounds of formula I, Ri is hydroxy, halogen, (Ci-C )alkyl, halo(C]-C6)alkyl, (C2-C6)alkenyl, (C2-C )alkynyl, cyclo(C -C )alkyl, (C|-C 6)alkoxy, halo(Ci-C 6)alkoxy, hydroxy(Ci-C )alkyl, cyano, (R6)2N- (C=0)-, (Ci-C )alkyl-S-, or heteroaryl; and/or R2 is H or (C[-C )alkyl; and/or R3 is H, (Ci-C )alkyl, halo(Ci-C 6)alkyl, or (C C6)alkoxy(Ci-C )alkyl; and/or R4 is H or (Ci-C 2)alkyl; and/or R5 is H, hydroxy, halogen, (Ci-C 6)alkyl, or (C1-C )alkoxy; and/or R is H; and/or i and R2 form, together with the carbon ring atoms to which they are attached, a condensed 6 or 7 membered saturated or unsaturated carbocyclic ring; for example R is hydroxy, halogen, (Ci-C3)alkyl, halo(Ci-C )alkyl, (C C )alkoxy, halo(Ci-C 3)alkoxy, or hydroxy(C i-C3)alkyl ; and/or R2 is H or (C C )alkyl; and/or R3 is H, (C C3)alkyl or halo(C,-C 3)alkyl; and/or R4 is H or methyl; and/or R is H, halogen or (C -C2)alkyl; and/or Ri and R2 form, together with the carbon ring atoms to which they are attached, a condensed 6 or 7 membered saturated or unsaturated carbocyclic ring; for example Ri is hydroxy, halogen,. (C -C3)alkyl, halo(Ci-C 3)alkyl, (C C )alkoxy, halo(C C3)alkoxy, or hydroxy(Ci-C )alkyl; and/or R2 is H or (C C )alkyl; and/or . R3 is H, (C C3)alkyl or halo(Ci-C 3)alkyl; and/or R4 is H or methyl; and/qr , R5 is H, halogen or (C -C2)alkyl; such as Ri is halogen, (Ci-C2)alkyl, halo(Ci-C 2)alkyl, (C -C2)alkoxy, or halo(C C2)alkoxy; and/or R2 is H; and/or R3.is H or (Ci-C2)alkyl; and/or R4 is H; and/or R5 is H. In further possible subgroup of the compounds of formula I, X is O. In yet another possible subgroup of the compounds of formula I, the compound is 2-(5-methylisochroman-l-yl)-4,5-dihydrO -lH -imidazole, 2-(5-bromoisochroman-l-yl)-4,5-dihydro-1 H-imidazole, 2-(l,5-dimethylisochroman-l-yl)-4,5-dihydro -lH -imidazole, 2-(5-chloroisochroman- -yl)-4,5-dihydro- 1H-imidazole, 1-(4,5-dihydro- 1H-imidazol-2-yl)isochroman-5-carbonitrile, 2-(5-allylisochroman-l-yl)-4,5-dihydro-l H-imidazole, 2-(5-vinylisochroman- -yl)-4,5-dihydro- 1H-imidazole, 2-(5-ethylisochroman- 1-yl)-4,5-dihydro- 1H-imidazole, 2-(5-ethylisochroman-l-yl)-4,5-dihydro-l H-imidazole hydrochloride, 2-(5-ethylisochroman-l-yl)-4,5-dihydro-lH-irnidazole sulfate, 2-(5-ethylisochroman-l-yl)-4,5-dihydro-lH-imidazole fumarate, l-(4,5-dihydro-lH-imidazol-2-yl)isochroman-5-ol, (l-(4,5-dihydro- 1H-imidazol-2-yl)isochroman-5-yl)methanol, 2-(5-bromo- 1-methylisochroman- 1-yl)-4,5-dihydro-lH-imidazole, 2-((3/?)-5-chloro-3-ethylisochroman-l-yl)-4,5-dihydro-lHimidazole, slower eluting isomer of l-(l-(4,5-dihydro-lH-imidazol-2-yl)-lmethylisochroman- 5-yl)-2,2-dimethylpropan-l-ol, faster eluting isomer of l-(l-(4,5-dihydro- 1H-imidazol-2-yl)- 1-methylisochroman-5-yl)-2,2-dimethylpropan- 1-ol, 2-(5-ethynylisochroman-l-yl)-4,5-dihydro-lH-imidazole, 2-((3R)-3-ethyl-5- (trifluoromethyl)isochroman- -yl)-4,5-dihydro- 1H-imidazole, 2-(5-methoxyisochroman- 1-yl)-4,5-dihydro-lH-imidazole, 2-(5-methoxyisochroman-l-yl)-4,5-dihydro-lH-imidazole hydrochloride, 2-(5-methoxyis0chroman-l-yl)-4,5-dihydro-lH-imidazole sulfate, 2-(5-methoxyisochroman-l-yl)-4,5-dihydro-l H-imidazole hemifumarate, 2-(5-iodoisochroman- 1-yl)-4,5-dihydro-l H-imidazole, 2-((3R)-3-methyi-5-(trifluorbmethyl)isochroman-l-yl)-4,5-dihydro-1 H-imidazole, 2-(5-bromd-4-methylisochroman-l-yl)-4,5-dihydro-l H-imidazole, faster eluting isomer of 2-(l,5-dimethylisochroman-l-yl)-4,5-dihydro-l H-imidazole, slower eluting isomer of 2-(l,5-dimethylisochroman-l-yl)-4,5-dihydro-lH-imidazole, 2-((3 R)-l,3,5-trimethylisochroman-l-yl)-4,5-dihydro-lH-imidazole, 2-(5-cyclopropylisochroman-lyl)- 4,5-dihydro-lH-imidazole, 2-(3,5-dimethylisochroman-l-yl)-4,5-dihydro-l H-imidazole, 2-(5-chlor0-3-methylisochroman-l-yl)-4,5-dihydro-lH-imidazole, 2-(3-ethyl-5-methylisochroman-l-yl)-4,5-dihydrO-lH-imidazole, 2-(5-chloro-l,3-dirriethylisochromari-lyl)- 4,5-dihydro-l H-imidazole, 2-(5-bromo-3-methylisochroman-l-yl)-4,5-dihydro-lHimidazole, 2-( 1,3,5-trimethylisochroman- -yl)-4,5-dihydro- 1H-imidazole, 2-(5-bromo- 1,3-dimethylisochroman- 1-yl)-4,5-dihydro- 1H-imidazole, 2-((3R)-5-bromo-3-methylisochroman-l-yl)-4,5-dihydro-lH-imidazole, 2-((3R)-5-chloro-3-methylisochromanl -yl)-4,5-dihydro-lH-imidazole, 2-((3S)-5-chloro-3-methylisochroman-l-yl)-4,5-dihydro- 1H-imidazole, 2-((35')-5-bromo-3-methylisochroman- 1-yl)-4,5-dihydro- 1H-imidazole, 2- ((3/?)-3,5-dimethylisochroman-l-yl)-4,5-dihydro-l H-imidazole, 2-((35)-3,5-dimethylisochroman- 1-yl)-4,5-dihydro- 1H-imidazole, 2-(5-methoxy-3-methylisochroman- 1-yl)-4,5-dihydro-l H-imidazole, 2-(5-ethyl-3-methylisochroman-l-yl)-4,5-dihydrO-lHimidazoie, 2-(5-bromo-3-propylisochroman-l-yl)-4,5-dihydro^lH-imidazole, 2-(5-isopropylisochroman- 1-yl)-4,5-dihydro- 1H-imidazole, 2-(5-fluoroisochroman- 1-yl)-4,5-dihydro- 1H-imidazole, 2-(5-bromo-3-ethylisochroman- 1-yl)-4,5-dihydro- 1H-imidazole, 2- ((3R)-5-methoxy-3-methylisochroman-l-yl)-4,5-dihydro-l H-imidazole, 2-((3R)-5-ethyl-3-methylisochroman-l-yl)-4,5-dihydro-lH-imidazole, 2-((3R)-5-ethyl-3-methylisochroman-lyl)- 4,5-dihydro-lH-imidazole hydrochloride, 2-((3R)-5-ethyl-3-methylisochroman-l-y])-4,5 dihydro- 1H-imidazole hemifumarate, 2-(3-ethyl-5-methoxyisochroman-l-yl)-4,5-dihydrolH-imidazole, 2-((3/?)-3,5-diethylisochroman-l-yl)-4,5-dihydro-lH-imidazole, 2-((3R)-3-ethyl-5-methylisochroman-l-yl)-4,5-dihydro-l H-imidazole, 2-((3R)-3-ethyl-5-methylisochroman- 1-yl)-4,5-dihydro- 1H-imidazole hydrochloride, 2-((3R)-3-ethyl-5-methylisochromati-'l-yl)-4,5-dihydro-lH-imidazole sulfate, 2-((3i?)-3^ethyl-5-methylisoehroman-l-yl)-4,5-dihydro-l H-imidazole hemifumarate, 2-((3R)-3-methyl-5- (triiluorometh0xy)isochroman l>yl)-4,5-dihydro-l H-imidazole, 2-((3R)^5-fluoro-3-rhethylisdchroman-l-yl^^^dihydro-lH-imidazole, 2-(5-ethoxyisochroman-l-yl)-4,5-dihydro- lH-imidazble, 2-(5-methyl-3-(2,2,2-trifluoroethyl)isochroman-l-yl)-4,5-dihydrolH-imidazole, 2-((35)-5-methoxy-3-methylisochroman-l-yl)-4,5-dihydro-lH-imidazole, 2- (5-(furan-3-yl)isochrdman-l-yl)-4,5-dihydro-l H-imidazole, 2-(5-(prop-l-yn-lyl) isochromari- 1-yl)-4,5-dihydro- 1H4midazole, -(4,5-dihydro- lH-imidazoi-2-yl)isochroman-5-carboxamide, 2-(3 ,7 ,8,9, , Oa-hexahydro- 1H-cyclohepta[de] isochromen- 3-yl)-4,5-dihydro-l H-imidazole, slower eluting isomer of l-(l-(4,5-dihydro-lH-imidazol-2-yl)isochroman-5-yl)ethanol, 2-(5,7-dimethylisochroman-l -yl)-4,5-dihydro-l H-imidazole, 2- (7-brom0-5-methylisochromah-l-yl)-4,5-dihydro-lH-imidazole, 2-(7-methoxy-5 methylisochroman-l^yl)-4,5-dihydro-lH-imidazole, 2-(3,5-dimethylisothiochroman-l-yl)- 4,5-dihydro-l H-imidazole, 2-(5-bromo-3-methylisothiochroman-l-yl)-4,5-dihydro-lHimidazole, 2-(5-methylisothiochroman-l-yl)-4,5-dihydro-lH-imidazole, 2-(5-bromoisothiochroman-l-yl)-4,5-dihydro-l H-imidazole, 2-(5-bromo-lmethylisothiochroman-l-yl)-4,5-dihydro-l H-imidazole, 2-(5,7-dibromo-3-ethylisochromanl-yl)-4,5-dihydro-l H-imidazole hydrochloride, enantiomer of 2-5-bromo-3-(2,2,2-trifluoroethyl)isochroman- 1-yl)-4,5-dihydro- 1H-imidazole hydrochloride, 2-(5-methoxy- -methylisochroman-l-yl)-4,5-dihydro-l H-imidazole, 2-(5-methoxyisofhiochroman-l-yl)-4,5-dihydro-1 H-imidazole, 2-((3/?)-5-methoxy-l,3-dimethylisochroman-l-yl)-4,5-dihydro-lHimidazole, 2-(5-(2,2,2-trifluoroethyl)isochroman- 1-yl)-4,5-dihydro- 1H-imidazole, 2-((3/?)-5 ethyl-l,3-dimethylisochroman-l-yl)-4,5-dihydro-lH-imidazole, 2-(5-methyl-3- (methoxymethyl)isochroman-l-yl)-4,5-dihydro-lH-imidazole, l-(4,5-dihydro-lH-imidazol- 2-yl)-5-methylisochroman-7-ol hydrobromide, l-(4,5-dihydro-lH-imidazol-2-yl)-3-ethylisochroman-5-ol hydrochloride, enantiomer-2 of 2-(5-methoxy-3-(2,2,2-trifluoroethyl)methylisochroman- l-yl)-4,5-dihydro- 1H-imidazole, 2-( 1,5-dimethylisothiochroman-l-yl)-4,5-dihydro-lH-imidazole, 2-(5- (trifluoromethoxy)isochroman- 1-yl)-4,5-dihydro- 1H-imidazole hydrochloride, enantiomerof 2-(3-ethylisochroman-l-yl)-4,5-dihydro-l H-imidazole hydrochloride, 2-(3-(2-fluoroethyl)-5-methylisochroman-l-yl)-4,5-dihydro-lH-imidazole hydrochloride, enantiomer of 2-(5-methoxyisochroman-l -yi)-4,5-dihydro- 1H-imidazole, enantiomer-2 of 2- 5-bromo-3-(2,2,2-trifluoroethyl)isochr0man^ 1-yl)-4,5-dihydro- 1H-imidazole hydrochloride, 2-(3-(2,2-difluoroethyi)-5-methylisochroman-l-yl)-4,5-dihydro-lH-imidazole hydrochloride, 2-(7-methoxy-3,5-dimethylisochroman-l-yl)-4,5-dihydro-l H-imidazole, enantiomer-2 of 2-((3)-5-methyl-3-(2,2,2-trifluoroethyl)isochroman-l-yl)-4,5-dihydro-lHimidazole hydrochloride, 2-(5-(methylthio)isochroman- l -yl)-4,5-dihydro- lH-imidazole, ' enantiomer-2 of 2-((3)-5-bromo-3-propylisochroman-l-yl) 4,5-dihydro-l H-imidazole hydrochloride, enantiomer-2 of 2-((3i?)-3-(2,2-difluoroethyl)-5-methylisochroman- 1-yl)-4,5-dihydro-1 H-imidazole hydrochloride, 2-(5-(difluoromethoxy)isochroman-l-yl)-4,5-dihydrolH-imidazole hydrochloride, 2-((3i?)-3-ethyl-5-methoxyisochroman-l -yl)-4,5-dihydro-lHimidazole, enantiomer- 1 of 2-(5-chloroisochroman-l-yl)-4,5-dihydro-lH-imidazole hydrochloride, 2-((3/?)-5-(difluoromethoxy)-3-methylisochroman-l-yl)-4,5-dihydro-lHimidazole hydrochloride, enantiomer of 2-(5-bromo-3-ethylisochroman-l-yl)-4,5-dihydro^ 1H-imidazole, enantiomer- 1 of 2-(5-chloroisochroman- -yl)-4,5-dihydro- 1H-imidazole hydrochloride, enantiomer-2 of 2-(3-ethylisochroman-l-yl)-4,5-dihydro-l H-imidazole, enantiomer-2 of 2-(5-methoxyoisochroman-l-yl)-4,5-dihydro-l H-imidazole hydrochloride, 2-( 1-methyl- 1,3-dihydrobenzo[de]isochromeh- 1-yl)-4,5-dihydro- 1H-i midazole, 2-(5- (difluoromethyl)isochroman-l-yl)-4,5-dihydro-l H-imidazole hydrochloride, enantiomer-2 of 2-(5-chloroisochroman-l-yl)-4,5-dihydro- l H-imidazole hydrochloride, enantiomer-2 of 2- (5-bromoisochroman-l-yl)-4,5-dihydro-lH-imidazole hydrochloride, 2-(l,3-dihydrobenzo[de]isochromen-l-yl)-4,5-dihydro-lH-imidazole hydrochloride, enatiomer of 2-(l -methyl- l,3-dihydrobenzb[de]isochromen-l-yl)-4,5-dihydro-l H-imidazole, 2-(3-methyll, 3-dihydrobenzo[de]isochromen-l-yl)-4,5-dihydro-lH-imidazole hydrochloride, 2-(3-ethyll, 3-dihydrobenzo[de]isochromen-l-yl)-4,5-dihydro-lH-inaidazole hydrochloride, or enantiomer of 2-(5-bromo-l-methylisochroman-l-yl)-4,5-dihydro-lH-imidazole. The terms employed herein have the meanings indicated below. The term "at least one" employed in the meanings below refers to one or several, such as one. For example, the term "at least one halogen" refers to one or several halogens, for example three, two or one halogens, such as three halogens. The term "hydroxy", as employed herein as such or as part of another group, refers to a -OH group. The term "halo" or "halogen", as employed herein as such or as part of another group, refers to fluorine, chlorine, bromine, or iodine. The term "(C C )alkyl", "(C,-C )alkyl", "(Ci-C 3)alkyl", and "(C,-C 2)alkyl", as employed herein as such or as part of another group, refers to a saturated straight or branched carbon chain having 1 to 6, 1 to 4, 1 to 3, and 1 to 2 carbon atom(s), respectively. Representative examples of (Ci-C6)alkyl, (Ci-C4)alkyl, (Ci-C 3)alkyl, and (Ci-C 2)alkyl include, but are not limited to, methyl, ethyl, rc-propyl, wo-propyl, n-butyl, iso-butyl, sec-butyl, rt-butyl, n-pentyl, iso-pentyl, and n-hexyl. The term "(C -C6)alkenyl" and "(C2-C3)alkenyl", as employed herein as such or as part of another group, refers to a straight or branched carbon chain having 2 to 6 and 2 to3 carbon atom(s), respectively, and containing at least one carbon-carbon douple bond. Representative examples of (C2-C )alkenyl and (C2-C3)alkenyl include, but are not limited to ethenyl and prop-2-en-l-yl. The term "(C2-C6)alkynyl", as employed herein as such or as part of another group, refers to a straight or branched carbon chain having 2, 3, 4, 5, or 6 carbon atom(s) and containing at least one carbon-carbon triple bond/Representative examples of (C -C6)alkynyl include, but are not limited to ethynyl, prop- 1-yn-l-yl and prop-2-ynyl. The term "cyclo(C 3-C6)alkyl" as employed herein as such or as part of another group, refers to a saturated hydrocarbon group having cyclic moiety and containing 3, 4, 5, or 6 carbon atom(s). Representative examples of cyclo(C3 -C6)alkyl include, but are not limited to cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. The term "(Ci-C )alkoxy" and "(C -C4)alkoxy", as employed herein as such or as part of another group, refers to an (Ci-C6)alkyl or an (C -C4)alkyl group, respectively, as defined herein, appended to the parent molecular moiety through an oxygen atom. Representative examples of (C -C )alkoxy and (Ci -C4)alkoxy include, but are not limited to, methoxy, ethoxy, «-propoxy, n-butoxy, wo-butoxy, ec-butoxy, reri-butoxy, 2,2-dimethylpropoxy, 3-methylbutoxy, and -hexoxy The term "halo(Ci-C )alkyl", as employed herein as such or as part of another group, refers to at least one halogen, as defined herein, appended to the parent molecular moiety through an -C alkyl group, as defined herein. When there are several halogens, the halogens can be attached to the same or different carbon atom and the halogens can be identical or different. Representative examples of halo(C 1-C6)alkyl include, but are not limited to, fluoromethyl, difluoromethyl, trifluoromethyl, 2-fluoroethyl, 2-cloroethyl, 2,2,2-trifluoroethyl, 1,2,2-trifluoroethyl, 2-cloropropyl, 3-fluoropropyl, 3-bromopropyl, 1,3-difluoropropyl, and 3,3,3-trifluoropropyl. The term "halo(Ci -C6 )alkoxy", as employed herein as such or as part of another group, refers to at least one halogen appended to the parent molecular moiety through an (Ci-C )alkoxy group, as defined herein. When there are several halogens, the halogens can be attached to the same or different carbon atom and the halogens can be identical or different. Representative examples of halo(Ci-C )alkoxy include, but are not limited to, fluoromethoxy, chloromethoxy, difluoromethoxy, trifluoromethoxy, 2-bromoethoxy, 2,2,2-trifluoroethoxy, 3-fluoropropoxy, 2-cloropropoxy, 3,3,3-trifluoropropoxy, and 4-fluorobutoxy. The term "halo(Ci-C )alkoxy(Ci-C6)alkyl", as employed herein as such or as part of another group, refers to an halo(Ci-C )alkoxy group, as defined herein, appended to the parent molecular moiety through a (C -C )alkyl group, as defined herein. The term "halo(Ci-C )alkoxy-halo(Ci-C )alkyl", as employed herein as such or as part of another group, refers to an halo(Ci-C )alkoxy group, as defined herein, appended to the parent molecular moiety through an halo(C -C )alkyl group, as defined herein. The term "(C -C )alkoxy-halo(Ci-C )alkoxy", as employed herein as such or as part of another group, refers to an (C -C6)alkoxy group, as defined herein, appended to the parent molecular moiety through an halo(Ci-C )alkoxy group, as defined herein. The term "carboxy", as employed herein as part of another group, refers to a -COOH group. The term "cyano", as employed herein as part of another group, refers to a -CN group. The term "oxo", as employed herein as part of another group, refers to a =0 group. The term "hydroxy(Ci-C 6)alkyl", as employed herein as such or as part of another group, refers to at least one hydroxy group, as defined herein, appended to the parent molecular moiety through an (Ci-C )alkyl group, as defined herein. Representative examples of hydroxy(Ci-C )alkyl include, but are not limited to, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 2,2-dihydroxyethyl, 1-hydroxypropyl, 3-hydroxypropyl, 1-hydroxy-lmethylethyl, 1-hydroxy- 1-methylpropyl, and 1-hydroxy-2,2-di methyl-prop- 1-yl. The term "hydroxy(C 2-C6 )alkehyl' *, as employed herein, refers to at least one hydroxy group, as defined herein, appended to the parent molecular moiety through an (C -C )alkenyl group, as defined herein. Representative examples of hydroxy(C 2-C )alkenyl include, but are not limited to, 1-hydroxyethenyl, 2-hydroxyethenyl, and l-hydroxyprop-2-enyl. The term "(Ci -C6 )alkoxy(C -C6)alkyl", as employed herein as such or as part of another group, refers to at least one (Ci-C )alkoxy group, as defined herein, appended to the parent molecular moiety through an (C -C )alkyl group, as defined herein. When there are several (Ci-C )alkoxy groups, the (Ci-C )alkpxy groups can be identical or different. Representative examples of (Ci-C )alkoxy(C 1-C )alkyl include, but are not limited to, methoxymethyl, ethoxymethyl, propoxymethyl, 2-methoxyethyl, 2-ethoxyethyl, 2,2-dimethoxyethyl, l-methyl-2-propoxyethyl, 1-methoxy-l-methylethyl, and 4-methoxybutyl. The term "hydroxy(Ci-C )alkoxy", as employed herein as such or as part of another group, refers to at least one hydroxy group, as defined herein, appended to the parent molecular moiety through an (C -C6)alkoxy group, as defined herein. Representative examples of hydroxy(C -C6)alkoxy include, but are not limited to, hydroxymethoxy, dihydroxymethoxy, 2-hydroxyethoxy, 2-hydroxypropoxy, 3-hydroxypropoxy, 2-hydroxybutoxy, and 2-hydroxy- 1-methylethoxy. 5 The term "hydroxy(Ci-C )alkoxy(Ci-C )alkyl", as employed herein as such or as part of another group, refers to an hydroxy(C -C )alkoxy group, as defined herein, appended to the parent molecular moiety through an (Ci-C )alkyl group, as defined herein. The term "(Ci-C6)alkoxy(C C6)alkoxy", as employed herein as such or as part of another group, refers to at least one (CrC )alkoxy group, as defined herein, appended to the parent 10 molecular moiety through an (C1-C6)alkoxy group, as defined herein. The (Ci-C )alkoxy groups can be identical or different. Representative examples of (Ci-C )alkoxy(Ci C )alkoxy include, but are not limited to, methoxymetho.xy, propoxymethoxy, 2-methoxyefhoxy, 2-ethoxyethoxy, 2-butoxyethoxy, 2,2-dimethoxyethoxy, l-methyl-2-propoxyefhoxy, 2-methoxypropoxy, and 15 4-methoxybutoxy. The term "(Ci-C )alkoxy(Ci-C6)alkoxy(Ci-C )alkyl", as employed herein as such or as part ,. , of another group, refers to an (C1-C )alkoxy(Ci -C6)alkoxy group, as defined herein, appended to the parent molecular moiety through an (Ci-C6)alkyl group, as defined herein. The term "phenyl", as employed herein as such or as part of another group, refers to 6 0 membered aromatic carbocyclic ring which can be unsubstituted or substituted with 1 or 2 substituent(s) each independently being hydroxy, halogen, (Ci-C4)alkyl, ( -G alkoxy, or halo(C C4)alkyl. The term "heteroaryl", as employed herein as such or as part of another group, refers to 3 to 7 membered aromatic monocyclic ring system, containing one to three heteroatom(s) 5 selected from oxygen, nitrogen and sulphur. Said heteroaryl can be unsubstituted or substituted with 1 or 2 substituent(s) each independently being hydroxy, halogen, oxo, ( - C4)alkyl, (Ci-C4)aIkoxy, or halo(C[-C )alkyl. Representative examples of heteroaryl include, but are not limited to furanyl, thiophenyl, and pyrazolyl. The term "heteroaryl(Ci-C )alkyl", as employed herein as such or as part of another group, refers to an heteroaryl, as defined herein, appended to the parent molecular moiety through an (C -C )alkyl group, as defined herein. The term "(C2-C6)alkenyloxy", as employed herein as part of another group, refers to an (C2-C6)alkenyl group, as defined herein, appended to the parent molecular moiety through an oxygen atom. Representative examples of (C -C6)alkenyloxy include, but are not limited to, ethenyloxy, prop-2-enyloxy, bute-2-nyloxy, and hex-3-enyloxy. The term "(C2-C )alkenyioxy(C2-C6)alkenyl", as employed herein, refers to at least one (C -C6 )alkenyloxy group, as defined herein, appended to the parent molecular moiety through an (C2-C )alkenyl group, as defined herein. When there are several (C2-C )alkenyloxy groups, the (C2-C6)alkenyloxy groups can be identical or different. Representative examples of (C2-C )alkenyloxy(C2-C6)alkenyl include, but are not limited to, ethenyloxyethenyl, and prop-2-enyloxyethenyl. The expression "compounds of the invention" as employed herein refers to the compounds of formula I. The "pharmaceutically acceptable salts" according to the invention include therapeutically active, non-toxic base and and acid salt forms, which the compounds of formula I are able to form with both organic and inorganic bases and acids. Representative examples of pharmaceutically acceptable base addition salt forms, for example, metal or amine salts, include, but are not limited to, ammonium salts, lithium, sodium, potassium, calcium, magnesium, aluminum and zinc salts, salts with organic bases, such as N-methyl-Dglucamine, hydrabamine salts and salts with amino acids, such as arginine, lysine, and the like. Representative examples of pharmaceutically acceptable acid addition salts include, but are not limited to, chlorides, bromides, sulfates, nitrates, phosphates, sulfonates, methane sulfonates, formates, tartrates, maleates, citrates, benzoates, salicylates, ascorbates, acetates, oxalates, fumarates, hemifumarates, and succinates. Pharmaceutically acceptable esters, when applicable, may be prepared by known methods using pharmaceutically acceptable acids that are conventional in the field of pharmaceuticals and that retain the pharmacological properties of the free form. Non-limiting examples of these esters include esters of aliphatic or aromatic alcohols. Representative examples of pharmaceutically acceptable esters include, but are not limited to, methyl, ethyl, n-propyl, iio-propyl, ra-butyl, wo-butyl, sec-butyl, tert-butyl, and benzyl esters. The invention includes within its scope all the possible geometric isomers, for example Z and E isomers (cis and trans isomers), of the compounds of the invention as well as all the possible optical isomers, such as diastereomers and enantiomers, of the compounds of the invention. Furthermore, the invention includes in its scope both the individual isomers and any mixtures thereof, such as a racemic mixture. The individual isomers may be obtained using the corresponding isomeric forms of the starting material or they may be separated after the preparation of the end compound according to conventional separation methods. For the separation of optical isomers, such as enantiomers, from the mixture thereof, conventional resolution methods, for example, fractional crystallization or preparative chiral chromatography, may be used. The compounds of formula I can be prepared by a variety of synthetic routes analogously or according to methods known in the literature using suitable starting ,materials, for example by reacting 2-phenylethanol or 2-phenylethanethiol with aldehyde or acetal, or according to other known methods (Larghi et al, Synthesis, 2006, 2, 187-220; Ishibashi et al, J Heterocyclic Chem 1985, 22, 1527-1529.). The imidazolenes can be prepared, for example, by reacting ethane- ,2-diamine with ester or aldehydes (Gentili et al, J. Med. Chem., 2003, 46, 2169-2176; Ishihara et al, Synthesis, 2007, 1939-1942). The starting materials depicted below are commercially available or can be prepared via synthetic routes known in the literature, for example, by reduction of carboxylic acid, carboxylic ester or ketones, by opening of corresponding epoxide with metalled aromatic species, by enzymatic hydrolysis or by chiral separation of racemic alcohol. (Bunnet et al, J. Org. Chem., 1962, 27, 3836-3843.; Mangas-Sanchez et al, Organic Lett, 2010, 12, 3498- 3501; Knolker et al, Tetrahedron Lett, 2000, 41, 1171-1 174.). In general, compounds of formula can be prepared analogously o according to the following scheme 1: Scheme 1. wherein a)SOCl , MeOH, b)NaBH4, c)TFA, 2,2-dihydroxyacetic acid, d) ethylenediamine, Me3Al, e) Pd(PPh3)4, HOCH SnBu . A person skilled in the art realizes that any starting material or intermediate in the reactions described above can be protected, if necessary, in a manner known in the art. Any protected functionality can subsequently be deprotected in a manner known in the art. The synthetic routes described above are meant to illustrate the preparation of the compounds of formula I and the preparation is by no means limited thereto, that is, there are also other possible synthetic methods which are within the general knowledge of a person sk led in the art. The compounds of formula I may be converted, if desired, into their pharmaceutically acceptable salt or ester forms using methods known in the art. The present invention will be explained in more detail by the following examples. The examples are meant for illustrating purposes only and do not limit the scope of the invention defined in the claims. The following general abbreviations are used: EtOAc = acetic acid ethyl ester, DCM = dichloromethane, HC1 =hydrochloric acid, MeOH = methanol, TFA=trifluoroacetic acid, THF = tetrahydrofurane, Et 0 = diethylether, Si0 = commercial silicon dioxide for chromatographic purposes (CAS 112926-00-8 or similar), hrs = hours, RT = room temperature. Microwave heating was performed using microwave reactors from Biotage. The structures of the products were confirmed by NMR. NMR resonances were measured on a Bruker Avance P400 MHz spectrometer and chemical shifts are quoted for selected compounds in parts-per-million (ppm) downfield relative to tetramethylsilane as internal standard. Separation Method A The reaction mixture was diluted with organic solvent (typically DCM or EtOAc) and washed with water or aqueous base (typically NH4OH, NaHC0 3 or NaOH) and dried over the drying agent (typically Na2S0 or K2C0 ), filtrated and evaporated. Separation Method B The reaction mixture was diluted with organic solvent (typically DCM or EtOAc) and washed with water or aqueous acid (typically HC1 or aqueus KHS0 4) and dried over the drying agent (typically Na2S0 4 or K2C0 3), filtrated and evaporated. Separation Method C The crude product was dissolved in organic solvent (typically DCM or EtOAc) and HC1 solution in solvent (typically EtOAc or Et20 ) was added and the solvents were evaporated or the precipitated solid was filtered. Separation Method D The precipitated solid was filtered, washed or recrystallized in the defined solvent or mixture of solvets to give the title compound. 5 Separation Method E The crude product was eluated trought a colum (commercial Si0 or CombiFlash instruments together with disposable Redisep columns from Teledyne ISCO) with mixture of solvent, typically EtOAc in heptan or MeOH in DCM eventually containing triethyl amine, ammonia or other basic modificator, from ratio 0/100/0 to 45/45/10, typically 5/94/1. 10 Separation Method F The reaction mixture was applied to acidic ion-exchange column and the column was washed with MeOH. The compound was eluated with MeOH containing 10 % aqueous NH3, triethylamine or similar amine base, filtrated and evaporated. Separation Method G 5 The crude product was eluated trought a reversed phase column (typically combiFlash instrument together with disposable Redisep Rf 18 columns from Teledyne ISCO) with , , mixture of solvent. Typically, a gradient of water/acetonitrile or methanol with 0. 1% ammonia or formic acid was used as eluent. Separation Method H 0 Separation was performed with preparative HPLC with a Agilent HPLC/UV purification system equipped with a Chiracel 1A column or OD-H column. Typically, an isocratic run of isopropanol/heptanes or hexanes from ratio 70/30 to 99/1 with 0.1% diethylamine or 0. % TFA was used as eluent. Separation Method I 5 Residue was taken in basic aqueous solution (typically NH OH, NaHC0 or NaOH) and the solution was washed with organic solvent (typically EtOAc, DCM or Et20). The aqueous phase was then made acidic by addition of acid (typically HC1) and extracted with organic solvent (typically Et 0 , EtOAc or DCM). The extract was dried (typically Na2S0 4 or K C0 ), filtered and evaporated. Separation Method J Residue was taken in acidic aqueous solution (typically HC1) and the solution was washed with organic solvent (typically EtOAc, DCM or Et20). The aqueous phase was then made basic by addition of basic aqueous solution (typically NH4OH, NaHC0 or NaOH) and extracted with organic solvent (typically Et 0 , EtOAc or DCM). The extract was dried (typically Na2SC>4 or K2C0 3), filtered and evaporated. Separation Method K The reaction mixture was evaporated to dryness and dissolved in MeOH. This was applied to pre-washed (MeOH) thiourea column. The compound was eluted with MeOH and evaporated. Separation Method L The enaniomers were separated with preparative HPLC UV purification system equipped with a Phenomenex LUX amylase-2 column. Typically, an isocratic run of nhexane/ ethanol/formic acid 70/30/0. 1 was used as eluent and fractions were acidified immediately after collection with aqueous HCI. Separation Method M Separation was performed with Thar SFC 80 preparative supercritical fluid HPLC system typically equipped with a Chiralpak AD-H column. Typically, an isocratic run of carbondioxane/methanol 93/7 or 90/10 was used as eluent. Preparation of the compounds of invention EXAMPLE 1: 2-(5-Methylisochroman-l-yI)-4,5-dihydro-lH-imidazole Synthesis Method A Synthesis Method Al: 5-Methylisochroman-l-carboxyIic acid The mixture of 2-(2-methylphenyl)ethanol (2 g), TFA (10ml) and 2,2-dihydroxyacetic acid ( 1.5 g) was refluxed for 23 hrs and volatiles were evaporated. Separation method I yielded the title compound (2.6 g) as an off-white solid. Alternatively, sulphuric acid can be used in cyclization. Synthesis Method A2: Methyl 5-methylisochroman-l-carboxyIate The mixture of 5-methylisochroman-l-carboxylic acid ( 1 g), methanol (20 ml) and trimethylsilylchloride (2 ml) was stirred for 1.5 hrs and volatiles evaporated. Separation method E yielded the title compound (0.5 g) as yellowish oil. Alternatively sulphuric acid can be used instead of trimethylsilylchloride. Synthesis Method A3: 2-(5-MethyIisochroman-l-yl)-4,5-dihydro-lH-imidazole To 10 minutes ice-bath cooled and stirred solution of ethylenediamine (0.29 ml), trimethylaluminum (2M heptane sol, 2.2 ml) and toluene (10 ml) was added the mixture of methyl 7-bromoisochroman-l-carboxylate (0.5 g) and. toluene (10 ml) and the reaction mixture was refluxed for 6 hrs. Water (2 ml), methanol (5 ml) and DCM (5 ml) were added, mixture refluxed for 15 min and participate was filtered off. Organics were evaporated and the title compound (0.38 g) was isolated with the separation method D (2-methoxy-2-methylpropane/MeOH). NMR (CDC13) d ppm 7.16 (s, 1H), 7.02 (s, 2H), 5.42 (s, 1H), 4.20 (ddd, 1H), 3.94 (br s, 1H), 3.84 (td, 2H), 3.39 (br s, 2H), 3.03 (ddd, 1H), 2.68 (d, 1H), 2.30 (s, 3 ) . EXAMPLE 2: 2-(5-Bromoisochroman-l-yl)-4,5-dihydro-lH-imidazoIe The title compound was prepared from 2-(2-bromophenyl)ethanol (200 mg) using the procedure of synthesis method A and separation methods A and E. (Yield 80 mg). Ή NMR (CDC13) d ppm 7.45 (d, 1H), 7.30 (d, 1H), 6.99 - 7. 10 (m, 1H), 5.72 (s, 1H), 4. 19 (ddd, 1H), 3.67 - 3.84 (m, 5H), 2.69 - 2.93 (m, 2H). EXAMPLE 3 : 2-(l,5-Dimethylisochroman-l-yl)-4,5-dihydro-lH-imidazole The mixture of NaH (0.77 g), methyl-5-methylisochroman-l-carboxylate (3 g, synthesis method A) and THF (40 ml) was stirred 75 min in ice-bath temperature, iodomethane (2.3 ml) was added and the mixture was stirred at ambient temperature for 3 hrs. The intermediate methyl 1,5-dimethylisochroman-l-carboxylate (2.5 g) was purified with separation method A and the title compound was synthesized using the procedure of synthesis method A step 3 and separation method D (2-propanol/heptanes). (Yield 1.0 g). NMR (CD3OD) d ppm 7.00 - 7. 18 (m, 3H), 3.99 (t, 2H), 3.54 (br s, 4H), 2.62 - 2.87 (m, 2H), 2.24 (s, 3H), 1.70 (s, 3H). EXAMPLE 4 : 2-(5-Chloroisochroman-l-yl)-4,5-dihydro-lH-imidazole Synthesis Method B The mixture of 2-(2-chlorophenyl)ethanol (1.0 g), ethyl 2,2-diethoxyacetate (1.7 g), titanium(rV)chloride (2.0 ml) and 1,2-dichloroethane (15 ml) was refluxed 1 hr. The intermediate ethyl 5-chloroisochroman-l-carboxylate was purified with separation methods B and E (0.41 g) and the title compound was synthesized using the procedure of synthesis method A3. Alternative boron trifluoride diethyletherate can be used instead of titanium(rV)chloride. (Yield 0.36 g). Ή NMR (CDC1 ) d ppm 7.20 - 7.40 ( , 2H, CHC13), 7.09 - 7.20 (m, IH), 5.41 (s, IH), 4.23 (ddd, IH), 3.77 - 4.00 (m, 3H), 3.28 - 3.51 (m, 2H), 2.77 - 3.01 (m, 2H). EXAMPLE 5 : l-(4,5-Dihydro-lH-imidazol-2-yl)isochroman-5-carbonitriIe A mixture of 2-(5-chloiOisochroman-l-yl)-4,5-dihydro-lH-imidazole (50 mg), dicyanozinc (25 mg), bis(tri-t-butylphosphine)palladium(0) (3mg) and DMF (2 ml) was stirred in microwave reactor at 160°C for 30 minutes. The title compound was purified with separation methods F and G. (Yield 22 mg). NMR (CD OD) d ppm 7.63 (dd, IH), 7.53 (d, IH), 7.35 (t, IH), 4.26 (ddd, IH), 3.92 (ddd, 1 H), 3.5 1 - 3.72 ( , 4H), 3.07 - 3.22 (m, IH), 2.89 - 3.03 (m, IH). EXAMPLE 6 : 2-(5-Allylisochroman-l-yl)-4,5-dihydro-lH-imidazole Synthesis Method C To a mixture of 2-(5-chloroisochroman-l-yI)-4,5-dihydro-l H-imidazoIe (50 mg), allyltributyltin (69.9 mg), CsF (70.6 mg) and bis(tri-t-butylphosphine)palladium (3.24 mg) were added dioxane (2 ml) and DMF (0.5 ml). The reaction mixture was degassed with N and heated in a microwave oven for 30 min at 160°C. The title compound was purified by applying methods F and G. (Yield 5.8 mg). Ή NMR (CD OD) d ppm 6.96 - 7.21 (m, 3H), 5.94 (ddt, IH), 4.92 - 5.08 (m, 2H), 4.22 (ddd, IH), 3.81 (ddd, IH), 3.52 (s, 4H), 3.34 - 3.35 (m, 2H), 2.93 (ddd, IH), 2.72 (dt, IH). EXAMPLE 7: 2-(5-Vinylisochroman-l-yl)-4,5-dihydro-lH-imidazole The title compound was prepared from 2-(5-bromoisochroman-l-yl)-4,5-dihydro-l -imidazole (100 mg) using the procedure of synthesis method C and purified with separation methods F and G. (Yield 5 mg). NMR (CDCI3) d pp 7.38 - 7.48 (m, 1H), 7.15-7.30 (m, 1H, CHC13), 6.80 - 7.05 (m, 2H), 5.74 (dd, 1H), 5.35 (dd, 1H), 4.25 (ddd, 1H), 3.50 - 3.85 ( , 5H), 2.80 - 3. 10 (m, 1H), 2.72 - 2.85 (m, 1H). EXAMPLE 8: 2-(5-Ethylisochroman-l-yI)-4,5-dihydro-lH-imidazole Synthesis Method D To a mixture of 2-(5-bromoisochroman-l-yl)-4,5-dihydro-lH-imidazole (100 mg), ethylboronic acid (56.2 mg), ( l , -bis(diphenylphosphino)ferrocene)dichloropalladium(II), complex with CH C (1: 1) (13 mg) and CsF (108 mg) was added dioxane (4 ml) and DMF ( l). The mixture was degassed with N and heated in a microwave oven for 30 min at 100°C and 30 min at 150°C. The title compound was purified by separation methods J and G. (Yield 6. 1 mg). Ή NMR (CD3OD) d ppm 6.96 -7.17 (m, 3H), 5.39 (s, 1H), 4.24 (ddd, 1H), 3.77 - 3.89 (m, 1H), 3.49 - 3.69 (m, 4H), 2.87 - 3.01 (m, 1H), 2.73 (dt, 1H), 2.63 (q, 2H), 1.20 (t, 3H). EXAMPLE 8 HC1 salt: 2-(5-Ethylisochroman-l-yl)-4,5-dihydro-lH-imidazole hydrochloride Salt formation Method A To the compound of example 8 ( g) in ethanol (15 ml) was added 4M hydrogen chloride in dioxane (160 mg) and the mixture was heated to reflux, allowed to cool and evaporated yielding the title compound (1.1 g). Alternative other solvents, temperatures and hydrogen chloride sources could be used, or product filtrated from solution or washed with other organic solvents. NMR (DMSO-d 6) d ppm 10.72 (s, 2H), 7. 14 - 7.24 (m, 3H), 5.91 (s, 1H), 4. 16 - 4.21 ( , 1H), 3.78-3.90 (m, 5H), 2.89 - 2.96 (m, 1H), 2.69-2.78 (m, 1H), 2.60 (q, 2H), 1.5 (tr, 3H). EXAMPLE 8 Sulfate salt: 2-(5-EthyIisochroman-l-yl)-4,5-dihydro-lH-imidazole sulfate Salt formation Method B To the compound of example 8 (1.5 g) in ethanol (30 ml) was added sulfuric acid (440 g) in ethanol (7.5 ml) and the mixture was heated to reflux, allowed to cool, evaporated and washed with acetone yielding the title compound (1.4 g). Alternative other solvents and temperatures could be used, or product filtrated from solution or washed with other organic solvents. NMR (DMSC 6) d ppm 7.13 - 7.25 (m, 2H), 7.05 (dd, 1H), 5.61 (s, 1H), 4.08 - 4. (m, 1H), 3.71 (br. s, 4H), 3.78 - 3.93 (m, 1H), 2.78 - 2.90 (m, 1H), 2.68 - 2.78 (m, 1H), 2.59 (q, 2H), 1.07 - 1.21 (m, 3H). EXAMPLE 8 Fumarate salt: 2-(5-Ethylisochroman-l-yI)-4,5-dihydro-lH-iniidazole fumarate Salt formation Method C To the compound of example 8 (2.3 g) in ethanol (15 ml) was added fumaric acid (1. 16 g) in ethanol (5 ml) and the mixture was heated to reflux, allowed to cool, evaporated and washed with TBME yielding the title compound (3.0 g). Alternative other solvents and temperatures could be used, or product filtrated from solution or washed with other organic solvents. Ή NMR (DMSO-d 6) d ppm 7. 15 - 7.20 (m, 2H), 7.05 - 7.09 (m, 1H), 6.48 (s, 2H), 5.72 (s, 1H), 4.14 - 4. 19 (m, 1H), 3.80 - 3.86 (m, lH), 3.71 (s, 4 H), 2.83 - 2.91 (m, 1H), 2.67-2.75 (m, lH), 2.58 (q, 2H), 1.15 (tr, 3H). EXAMPLE 9 : l-(4,5-Dihydro-lH-imidazol-2-yl)isochroman-5-ol A mixture of 2-(5-bromoisochroman-l-yl)-4,5-dihydro-lH-imidazole (720 mg), bis(pinacolato)diboron (715 mg) bis(tri-t-butylphosphine)palladium(0) (39 mg), potassiumacetate (503 mg), dioxane (9 ml) and DMF (0.75 ml) was stirred under inert atmosphere in microwave reactor at 160°C for 30 minutes. Additonal bis(tri-tbutylphosphine) palladium(O) (21 mg) was added and heating continued for 5 minutes. The intermediate 2-(5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)isochroman-l-yl)-4,5-dihydro-lH-imidazole (680 mg) was purified with separation method A and stirred with EtOAc (2 ml), water (2 ml) and hydrogen peroxide (35%, 0.07 ml) at ice bath temperature for 2 hrs. The title compound was purified with separation methods A and E. (Yield 45 mg). NMR (DMSO-d ) d ppm 9.44 (s, 1H), 6.78 - 7.08 (m, 1H), 6.62 (d, 1H), 6.67 (d, 1H), 5.22 (s, 1H), 4.05 - 4.15 ( , 1H), 3.70 - 3.78 (m, 1H), 3.18 - 3.42 (m, 4H, H20), 2.53-2.69 (m, 2H). EXAMPLE 10: (l-(4,5-Dihydro-lH-imidazol-2-yl)isochroman-5-yl)methanol The title compound was prepared from 2-(5-bromoisochroman-l-yl)-4,5-dihydro-lHimidazole (50 mg) and (tributylstannyl)methanol (86 mg) by using tetrakis(triphenylphosphine) palladium (10.28 mg) as catalyst, and the procedure of synthesis method C and separation methods F and G. (Yield 6.2 mg). Ή NMR (CD3OD) d ppm 7.3 1 (d, 1H), 7. 1 - 7.22 (m, 2H), 5.42 (s, 1H), 4.62 (s, 2H), 4.22 (td, 1H), 3.86 (dd, 1H), 3.54 - 3.69 (m, 4H), 2.93 - 3.05 (m, 1H), 2.75 - 2.86 ( , 1H). EXAMPLE 11: 2-(5-Bromo-l-methylisochroman-l-yl)-4,5-dihydro-lH-imidazole The mixture of NaH (0.024 g), ethyl 5-bromoisochroman-l-carboxylate (0.2 g, synthesis method B) and THF (5 ml) was stirred 90 min in ice-bath temperature, iodomethane (0.06 ml) was added and the mixture stirred at ambient temperature for 16 hrs. The intermediate ethyl 5-bromo-l-methylisochroman-l-carboxylate (0. 1 g) was purified with separation method A, and the title compound was synthesized using the procedure of synthesis method A3 and separation method E (DCM/EtOAc/Et N). (Yield 0.07 g). Ή NMR (CDCI ) d ppm 7.45 - 7.47 (m, 1H), 7.39 - 7.41 (m, 1H), 7.07 - 7.1 1 (m, 1H), 4.70 - 5.20 (br s, 1H), 3.94 - 4.05 ( , 2H), 3.22 - 3.87 (m, 2H), 2.83 - 2.87 (m. 2H), 1.77 (s, 3H). EXAMPLE 12: 2-((3R)-5-chloro-3-ethylisochroman-l-yl)-4,5-dihydro-lH-imidazoIe The title compound was prepared from (R )-l-(2-chlorophenyl)butan-2-ol (400 mg) using the procedure of synthesis methods B and A3. Intermediate (3/?)-ethyl 5-chloro-3-ethylisochroman-l-carboxylate was purified with separation methods B (EtOAc/Heptane) and E. (Yield 235 mg). Ή NMR (DMSO-4) d ppm 7.28 - 7.43 (m, 1H), 7. 1 - 7.26 (m, 2H), 6.12 (br s, 1H), 5.35 (s, 1H), 3.53 - 3.80 (m, 3H), 3. 12 - 3.29 (m, 2H), 2.73 - 2.92 (m, 1H), 1.67 (m, 2H), 0.99 (t, 3H). EXAMPLE 13: l-(l-(4,5-Dihydro-lH-imidazol-2-yl)-l-methylisochroman-5-yl)-2,2-dimethylpropan-l-ol, slower eluting isomer To a solution of 2-(5-brorno-l-rnethylisochrornan-l-yl)-4,5-dihydro-lH-imidazole (Example 2, 0.075 g) in 2ml of THF was added 0.33 ml of tert-butyl lithium solution in pentane ( 1.7M) at -78°C followed by addition of 1 2ml of 20.8M solution of trimethylacetaldehyde in THF. After stirring at -78°C for 15 min, the reaction was quenched with ice. The title compound was isolated with separation methods A and G. (Yield 0.003 g). Ή NMR (CDC13) d ppm 7.43 - 7.45 (m, 1H), 7.34 - 7.36 (m, 1H), 7.22 - 7.24 ( , 1H), 4.73 (s, 1H), 3.88 - 4.05 (m, 2H), 3.61 (br s, 4H), 2.84 - 2.91 (m, 2H), 1.78 (s, 3H), 0.97 (s, 9H). EXAMPLE 14: l-(l-(4,5-Dihydro-lH-imidazoI-2-yI)-l-methylisochroman-5-yl)-2,2-dimethylpropan-l-ol, faster eluting isomer The title compound was isolated in the synthesis of the example 13 with separation methods A and G. (Yield 0.007 g). NMR (CDCI3) d ppm 7.46 (d, 1H), 7.50 (d, 1H), 7.18 - 7.35 (m, 3H), 4.72 (s, 1H), 4.04 (s, 1H), 3.59 - 3.81 (m, 3H), 2.81 - 3.02 (m, 2H), 2.05 (d, 1H), 1.89 (s, 3H), 0.86 - 1.05 (m, 9H). EXAMPLE 15: 2-(5-EthynyIisochroman-l-yl)-4,5-dihydro-lH-imidazole To a degassed solution of 2-(5-bromoisochroman-l-yl)-4,5-dihydro-lH-imidazole (300 mg) in Et N (10 ml) and ethynyltrimethylsilane (210 mg) was added tetrakis(triphenylphosphine) -palladium (37 mg). The mixture was degassed with N and heated in a microwave oven for 60 min at 120°C. The reaction mixture was concentrated under vacuum and purified by separation method K. K C0 was added to the reaction crude (in MeOH) and the mixture was stirred 4h at rt. The title compound was isolated by a separation method G. (Yield 6.2 mg). Ή NMR (CDCI3) d ppm 7.42 - 7.37 (m, 2H), 7.17 (t, 1H), 5.42 (s, 1H), 4.78 (s, 1H), 4.26 - 4.21 (m, H), 4.00 - 3.73 (m, 4H), 3.08 - 2.93 (m, 2H). EXAMPLE 16: 2-((3/?)-3-ethyl-5-(trifluoromethyl)isochroman-l-yl)-4,5-dihydro-lHimidazole Step 1: (/?)-l-(2-(trinuoromethyl)phenyl)butan-2-ol 2-Iodobenzotrifluoride (3 g) was dissolved in THF (18 ml) and was cooled to -78 °C. n- BuLi (2.5 M in hexanes, 13.23 ml) was added dropwise to the reaction mixture. After 1 h, (/?)-(+)- 1,2-epoxybutane (1.4 ml) in THF (18 ml) was added. The reaction temperature was slowly increased to rt. The mixture was poured into ice-water (100 ml), and the product was extracted with heptane. The organic phase was washed with brine and water, dried (Na2S0 4) j a evaporated under vacuum. The title compound was obtained by separation method E. (Yield 1.05 g). Step 2 : 2-((3R)-3-ethyl-5-(trifluoromethyl)isochroman-l-yl)-4,5-dihydro-lH-imidazole The title compound was prepared from (/?)-l-(2-(trifluoromethyl)phenyl)butan-2-ol (570 mg) using the procedure of synthesis methods B and A3. Intermediate (3/?)-ethyl 5-trifluoromethyl-3-ethylisochroman- l-carboxylate was purified with separation methods B (EtOAc/Heptane) and E. (Yield 360 mg). Ή NMR (CD OD) d pp 7.59 (d, 1H), 7.50 (d, 1H), 7.25 - 7.42 (m, 1H), 5.49 (s, 1H , 3.46 - 3.72 (m, 5H), 2.98 (d, 1H), 2.82 (dd, 1H), 1.59 - 1.84 (m, 2H), 0.97 - 1. 18 (m, 3H). EXAMPLE 17: 2-(5-Methoxyisochroman-l-yl)-4,5-dihydro-lH-imidazole Synthesis Method E To a mixture of 2-(5-bromoisochroman- -yl)-4,5-dihydro- 1H-imidazole (200 mg), 2-(di-tbutylphosphino) biphenyl (5.31 mg), palladium(II)acetate (3.19 mg) and Cs2C0 3 (348 mg) was added methanol ( 1 ml) and toluene (2 ml). The mixture was degassed with N and then heated for 40 min at 120°C and 30 m n at 130°C. Alternatively, other Pd-ligand complexes and reaction conditions can be applied in the C-O formation. The title compound was purified by using separation methods E and G. (Yield 5 mg). NMR (CD3OD) d ppm 7.14 (t, 1H), 6.80 (d, 1H), 6.83 (d, 1H), 5.34 (s, 0.3H), 4. 16 - 4.3 1 (m, 1H), 3.74 - 3.89 (m, 4H), 3.50 - 3.68 (m, 4H), 2.61 - 2.90 (m, 2H). EXAMPLE 17 HC1 salt: 2-(5-Methoxyisochroman-l-yI)-4,5-dihydro-lH-imidazole hydrochloride The title compound was prepared from compound of example 17 (263 mg) as described in the example 8 (Et20 , yield 148 mg). Ή NMR (CDjOD) d ppm 7.28 (t, 1H), 6.97 (d, 1H), 6.80 (d, 1H), 5.72 (s, 1H), 4.12 - 4.19 (m, 1H), 3.99 (br.s, 4H), 3.87-3.95 ( , 1H), 3.86 (s, 3H), 2.78 - 2.84 (m, 2H). EXAMPLE 17 Sulfate salt: 2-(5-Methoxyisochroman-l-yl)-4,5-dihydro-lH-imidazole sulfate The title compound was prepared from compound of example 7 (50 mg) as described in the example 8 (EtOH, yield 41.5 mg). NMR (DMSO- ) d ppm 9.37-10.57 (br, 2H), 7.27 (t, 1H), 6.99 (d, 1H), 6.79 (d, 1H), 5.75 (s, 1H), 4.03 - 4.20 (m, 1H), 3.85-3.94 (m, 5H), 3.82 (s, 3H), 2.65 - 2.79 (m, 2H). EXAMPLE 17 Hemifumarate salt: 2-(5-Methoxyisochroman-l-yl)-4,5-dihydro-lHimidazole hemifumarate The title compound was prepared from compound of example 7 (50 mg) as described in the example 8 (EtOH, yield 38 mg). NMR (DMSO-4) d ppm 7. 16 (t, lH), 6.88 (d, 1H), 6.79 (d, 1H), 6.43 (s, 1H), 5.47 (s, 1H), 4.07 - 4.16 (m, 1H), 3.73-3.82 (m, 4H), 3.40-4.75 (br.s, 4H), 2.58 - 2.75 (m, 2H). EXAMPLE 18: 2-(5-Iodoisochroman-l-yl)-4,5-dihydro-lH-imidazole The title compound was prepared from 2-(2-iodophenyl)ethanol (1.5 g) using the procedure of synthesis method B and separation method D. (Yield 510 mg). NMR (CD OD) d ppm 7.72 - 7.84 (m, lH), 7.24 (d, 1H), 6.94 (t, 1H), 4.21 (ddd, 1H), . 3.83 (ddd, lH), 3.46 - 3.68 (m, 4H), 2.80 - 2.95 (m, 1H), 2.56 - 2.74 (m, 1H). EXAMPLE 19: 2-((3R)-3-methyl-5-(trifluoromethyI)isochroman-l-yl)-4,5-dihydro-lHimidazole The title compound was prepared from (/?)-l-(2-(trifluoromethyl)phenyl)propan-2-ol (570 mg) using the procedure of synthesis methods B and A3. Starting material (/?)-l-(2- (trifluoromethyl)phenyl)propan-2-ol ( .0 g) was prepared from 2-iodobenzotrifuoride and (/?)-(+)-propyleneoxide in a similar way that described in the example 16. Intermediate (3R)-ethyl 5-trifluoromethyl-3-ethylisochroman-l-carboxylate was purified with separation methods B (EtOAc/Heptane) and E. (Yield 340 mg). NMR (CD3OD) d ppm 7.59 (d, 1H), 7.50 (d, 1H), 7.29 - 7.43 ( , 1H), 5.51 (s, 1H), 3.83 - 3.97 (m, 1H), 3.49 - 3.72 (m, 4H), 2.99 (d, 1H), 2.82 (dd, 1H), 1.25 - 1.48 (m, 3H). EXAMPLE 20: 2-(5-Bromo-4-methylisochroman-l-yI)-4,5-dihydro-lH-imidazole The title compound was prepared from 2-(2-bromophenyl)propan-l-ol ( 1.55 g) using the procedure of synthesis method B and separation method E. (Yield 70 mg). NMR (CD3OD) d ppm 7.43 - 7.55 ( , 1H), 7.27 (d, 0.6H), 7.04 - 7. 15 ( , 1.4H), 5.34 (s, 0.5H), 3.98 - 4.10 (m, 1H), 3.75 - 3.92 (m, 1H), 3.53 - 3.67 (m, 4H), 2.94 - 3.06 (m, 1H), 1.45 (d, 1.9H), 1.33 (d, 1. 1H). EXAMPLE 21: 2-(l,5-Dimethylisochroman-l-yI)-4,5-dihydro -lH-imidazole, faster eluting isomer The title compound was prepared from 2-(l,5-dimethylisochroman-l-yl)-4,5-dihydro-lHimidazole (Example 3, 70 mg) using the procedure of separation method H. (Yield 22 mg). Ή NMR (CDCI3) d ppm 7. 19 - 7.40 (m, 1H, CHC1 ), 7.02 - 7.19 (m, 2H), 3.90 - 4. 15 ( , 2H),' 2.66 - 2.81 (m, 2H), 2.24 (m, 3H), 1.79 (s, 3H). EXAMPLE 22: 2-(l,5-DimethyIisochroman-l-yI)-4,5-dihydro -lH-imidazoIe, slower eluting isomer The title compound was prepared from 2-(l,5-dimethylisochroman-l-yl)-4,5-dihydro-lHimidazole (Example 3, 70 mg) using the procedure of separation method H. (Yield 9 mg). Ή NMR (CDCI3) d ppm 7.21 - 7.36 (m, 1H, CHCI3), 7.01 - 7.18 (m, 2H), 3.91 - 4.15 (m, 2H), 2.60 - 2.83 (m, 2H), 2.24 (s, 3H), 1.79 (s, 3H). EXAMPLE 23: 2-((3R)-l,3,5-trimethylisochroman -l-yl)-4,5-dihydro -lH-imidazole The title compound was prepared from (3R )-methyl 3,5-dimethylisochroman- l-carboxylate (454 g, example 33 intermediate) using the procedure of example 1 and separation method E (DCM/EtOAc/Et3N). (Yield 232 mg). NMR (DMSO - ) d ppm 7.12 - 7.23 (m, 1H), 6.93 - 7.12 (m, 2H), 6.15 (s, 0.5H), 5.83 (s, 0.5H), 3.87 - 4.02 (m, 0.5H), 3.61 - 3.86 (m, 1H), 3.40 - 3.61 (m, 1.5H), 3.04 - 3.29 (m, 2H), 2.53 - 2.71 (m, 1H), 2.27 - 2.48 (m, 1H), 2.18 (s, 1.5H), 2. 16 (s, 1.5H), 1.64 (s, 1.5H), I .56 (s, 1.5H), 1.23 - 1.38 (m, 3H). EXAMPLE 24: 2-(5-Cyclopropylisochroman-l-yI)-4,5-dihydro-lH-imidazole The mixture of 2-(5-bromo-l-methylisochroman-l-yl)-4,5-dihydro-lH-imidazole (Example I I, 0.15g), sodium carbonate (0.27g), bis(triphenylphosphine)palladium(II) chloride (0.02g), cyclopropylboronic acid (0.09g), water (1ml), and acetonitrile (2ml) was heated in a microwave oven at 120°C for 5 min. The title compound was purified with separation methods A and G. (Yield 8 mg). NMR (CDC1 ) d ppm 7.26 - 7.28 (d, 1H), 7.1 - 7.15 (tr, 1H), 6.92 - 6.94 (d, 1H), 4.03 - 4.06 (m, 2H), 3.62 (br s, 4H), 2.95 - 2.98 (m, 2H), 1.80 (s, 3H), 0.87 - 0.96 (br , 2H), 0.58 - 0.69 (br m, 2H). EXAMPLE 25: 2-(3,5-Dimethylisochroman-l-yI)-4,5-dihydro-lH-imidazole The title compound was prepared from l-o-tolylpropan-2-ol (800 mg) using the procedure of synthesis method B and separation methods E and D. (Yield 19.2 mg). NMR (CD OD) d ppm 6.98 - 7.1 1 (m, 3H), 5.43 (s, 1H), 3.88 (dd, 1H), 3.49 - 3.67 (m, 4H), 2.64 - 2.76 (m, 1H), 2.57 (d, 1H), 2.23 (s, 3H), 1.39 (d, 3H). EXAMPLE 26: 2-(5-Chloro-3-methylisochroman-l-y!)-4,5-dihydro-lH-imidazo!e The title compound was prepared from l-(2-chlorophenyl)propan-2-ol ( 0g) using the procedure of synthesis method A and separation methods A and D (Et20 , heptane). (Yield 0.077g). NMR (DMSO-d 6) d ppm 7.32 - 7.37 (m, 1H), 7.14 - 7.23 (m, 2H), 6.23 (br s, 1H), 5.36 (s, 1H), 3.83 - 3.91 (br m, 1H), 3.43 (br s, 4H), 2.82 - 2.89 (m, 1H), 2.46 - 2.53 (m, 1H), 1.29 - 1.34 (dd, 3H). EXAMPLE 27: 2-(3-Ethyl-5-methyIisochroman-l-yI)-4,5-dihydro-l H-imidazoIe The title compound was prepared from l-o-tolylbutan-2-ol ( 1 g) using the procedure of synthesis method B and separation methods E and D. (Yield 16.4 g). H NMR (CD OD) ppm 6.93 - 7. 1 ( , 3H), 5.41 (s, 1H), 3.45 - 3.72 (m, 6H), 2.71 (dd, 1 H), 2.55 (dd, 1H), 2.17 - 2.26 (m, 3H), 1.62 - 1.78 (m, 2H), 0.98 - 1. 14 (m, 3H). EXAMPLE 28: 2-(5-Chloro-l,3-dimethylisochroman-l-yI)-4,5-dihydro-lH-imidazole The mixture of NaH (0.36g), methyl 5-chloro-3-methylisochroman-l-carboxyIate ( l .lg, synthesis method A) and THF (20 ml) was stirred 60 min in ice-bath temperature, iodomethane (0.9 ml) was added and the mixture stirred at ambient temperature for 16 hrs. The intermediate methyl 5-chloro-l,3-dimethylisochroman-l-carboxylate (0.95g) was purified with separation method A and the title compound was synthesized using the procedure of synthesis method A and separation method A. (Yield 0. lg). Ή NMR (DMSO-d 6) d ppm 7. 16 - 7.33 (m, 3H), 6.14 (br s, 1H), 3.72 - 4.02 (br m, 1H), 3.40 - 3.47 (br s, 2H), 2.76 - 2.86 (br s, 1H), 2.35 - 2.54 (br m, 1H), 1.60 - 1.66 (d, 3H), 1.30 - 1.32 (dd, 3H). EXAMPLE 29: 2-(5-Bromo-3-methyIisochroman-l-y!)-4,5-dihydro-lH-imidazole The title compound was prepared from l-(2-bromophenyl)propan-2-ol (2.5 g) using the procedure of synthesis method A (43% of prepared methyl 5-bromo-3-methyl-isochroman- 1-carboxylate was used in the last step) and separation method D. (Yield 447 mg). NMR (CD OD) d ppm 7.42 - 7.55 (m, 1H), 7.24 (d, 0.8H), 7.02 - 7.17 (m, 1.2H), 5.41 (s, 0.7H), 4.08 (s, 0.2H), 3.81 - 3.95 (m, 0.8H), 3.50 - 3.70 (m, 4H), 2.82 - 2.93 (m, 1H), 2.40 - 2.64 (m, 1H), 1.38 - 1.44 (m, 2.3H), 1.34 (d, 0.7H). EXAMPLE 30: 2-(l,3,5-Trimethylisochroman-l-yI)-4,5-dihydro-l H-imidazole The title compound was prepared from l-o-tolylpropan-2-ol (0.9g) using the methodolgy as described in example 12 with the exception of using separation methods A and D (Et20 and heptanes) in the final synthesis step. (Yield 0.012g). NMR (DMSO-d6) ppm 7.27 - 7.29 (d, 1H), 7. 13 - 7.17 (tr, 1H), 7.05 - 7.07 (d, IH), 4.85 (br s, IH), 3.82 - 3.90 (m, IH), 3.64 (br s, 4H), 2.59 - 2.64 (m, H), 2.44 - 2.51 ( , IH), 2.21 - 2.23 (m, 3H), 1.72 (s, 3H), 1.37 -1.38 (d, 3H). EXAMPLE 31: 2-(5-Bromo-l,3-dimethylisochroman-l-yl)-4,5-dihydro-lH-imidazole The title compound was prepared from l-(2-bromophenyl)propan-2-ol (2.5 g) using the procedure of synthesis method A. After the first two steps, 43% (500 mg) of the prepared methyl 5-bromo-3-methyl-isochroman-l-carboxylate was dissolved in THF (5 ml). NaH (140 mg) was added to the solution and then the mixture was stirred at ice-bath temperature. After 60 min iodomethane (0.325 ml) was added and the mixture stirred at ambient temperature for 48 hrs. The intermediate methyl 5-bromo-l ,3-dimethylisochroman-lcarboxylate was purified with separation methods A and E (168 mg) and the title compound was synthesized using the procedure of synthesis method A (step 3) and separation method D. (Yield 24 mg). Ή NMR (CD OD) d ppm 7.41 - 7.54 (m, IH), 7.25 - 7.37 (m, IH), 7.03 - 7.17 (m, IH), 4.04 (ddd, .2H), 3.76 - 3.90 ( , 0.8H), 3.44 - 3.64 (m, 4H), 2.78 - 2.95 ( , IH), 2.37 - 2.62 (m, IH), 1.74 (s, 0.6H), 1.68 (s, 2.4H), 1.32 - 1.41 (m, 3H). EXAMPLE 32: 2-((3R)-5-bromo-3-methylisochroman-l-yl)-4,5-dihydro-lH-imidazole The title compound was prepared from (R )-l-(2-bromophenyl)propan-2-ol (400 mg) using the procedure of synthesis method A and separation method D (heptane). (Yield 75 mg). H NMR (CD OD) d ppm 7.49 (d, 1H), 7.24 (d, IH), 7.02 - 7. 18 (m, IH), 5.42 (s, IH), 3.76 - 3.97 (m, IH), 3.51 - 3.72 (m, 5H), 2.75 - 2.96 (m, IH), 2.58 (dd, IH), 1.22 - 1.51 (m, 3H). EXAMPLE 33: 2-((3R)-5-chloro-3-methylisochroman-l-yl)-4,5-dihydro-lH-imidazoIe The title compound was prepared from (R)- \ -(2-chlorophenyl)propan-2-ol (0.3g) using the procedure of synthesis method A and separation methods A and D (Et 0 and heptane). (Yield 0.03g). NMR (DMSO-d ) d ppm 7.35 - 7.37 (d, IH), 7. 17 - 7.23 (m, 2H), 6.14 (br s, IH), 5.36 (s, IH), 3.83 - 3.91 ( , IH), 3.6 (br m, 2H), 3. 10 - 3.30 (br s, 2H), 2.82 - 2.86 (d, IH), 2.46 - 2.53 (d, IH), 1.33 - 1.34 (d, 3H). EXAMPLE 34: 2-((3S)-5-chloro-3-methylisochroman-l-yI)-4,5-dihydro-lH-imidazole The title compound was prepared from (5)-l-(2-chlorophenyl)propan-2-ol (0.3g) using the procedure of synthesis method A and separation methods A and E (Et 0 and heptane). (Yield 0.03g). Ή NM (CDC13) d ppm 7.34 - 7.36 (d, 1H), 7.28 - 7.30 (d, 1H), 7.1 1 - 7.15 (tr, 1H), 5.54 (br s, 1H), 3.86 - 3.94 (m, 1H), 3.56 - 3.76 (br m, 4H), 2.89 - 2.94 (dd, 1H), 2.54 - 2.61 (m, 1H), 1.37 - 1.43 (m, 3H). EXAMPLE 35: 2-((3S)-5-bromo-3-methylisochroman-l-yl)-4,5-dihydro-lH-imidazole The title compound was prepared from (S)-l-(2-bromophenyl)propan-2-ol (200 mg) using the procedure of synthesis method A and separation methods D (Et 0 ) and G. (Yield 23 mg). Ή NMR (CD3OD) d ppm 7.38 - 7.60 (m, lH , 7.23 (d, 1H), 7.03 - 7.18 ( , 1H), 5.42 (s, 1H), 4.03-4.13 (m, 0.3H), 3.79 - 3.98 (m, 0.7H), 3.43 - 3.71 (m, 4H), 2.81 - 2.97 (m, 1H), 2.58 (dd, 0.7H), 2.46 (dd, 0.3H), 1.34 - 1.40 (m, 3H). EXAMPLE 36: 2-((3R)-3,5-dimethylisochroman-l-yl)-4,5-dihydro-lH-imidazole The title compound was prepared from (/?)-o-tolylpropan-2-ol (400 mg) using the procedure of synthesis method A and separation method E. (Yield 40 mg). NMR (CD3OD) d ppm 6.99 - 7. 1 (m, 3H), 5.43 (s, 1H), 3.88 (ddd, 1H), 3.53 - 3.66 (m, 4H), 2.72 (dd, 1H), 2.47 - 2.61 (m, lH), 1.39 (d, 3H). EXAMPLE 37: 2-((3S)-3,5-dimethylisochroman-l-yl)-4,5-dihydro-lH-imidazole The title compound was prepared from (S)-o-tolylpropan-2-ol (400 mg) using the procedure of synthesis method A and separation methods E and D. (Yield 40 mg). Ή NMR (CD3OD) d ppm 6.99 - 7.13 (m, 3H), 5.43 (s, 1H), 3.82 - 3.93 (m, 1H), 3.53 - 3.66 (m, 4H), 2.66 - 2.79 ( , 1H), 2.48 - 2.62 (m, 1H), 1.39 (d, 3H). EXAMPLE 38: 2-(5-Methoxy-3-methyIisochroman-l-yl)-4,5-dihydro-lH-imidazole The title compound was prepared from 2-(5-bromo-3-methylisochroman-l-yl)-4,5-dihydroIH-imidazole (200 mg) using the procedure of synthesis method E and separation methods K and G. (Yield 5.8 mg). NMR (CD OD) d ppm 7.07 - 7.18 (m, IH), 6.76 - 6.87 (m, 2H), 5.41 (s, H), 3.76 - 3.87 (m, 4H), 3.55 - 3.67 (m, 4H), 2.83 (dd, IH), 2.42 (dd, IH), 1.31 - 1.41 (m, 3H). EXAMPLE 39: 2-(5-Ethyl-3-methylisochroman-l-yl)-4,5-dihydro-lH-imidazole The title compound was prepared from 2-(5-bromo-3-methylisochroman-l-yl)-4,5-dihydrolH-imidazole (200 mg) using the procedure of synthesis method D and separation methods J and G. (Yield 18.4 mg). Ή NMR (CD3OD) d ppm 7.04 - 7.14 (m, 2.6H), 6.96 - 7.01 (m, 0.4H), 5.45 (s, 0.7H), 4. 11 (s, 0.2H), 3.87 (ddd, 0.8H), 3.51 - 3.66 (m, 4H), 2.75 - 2.89 (m, IH), 2.54 - 2.70 (m, 3H), 1.37 - 1.43 ( , 2.3H), 1.33 (d, 0.7H), 1.20 (t, 3H). EXAMPLE 40: 2-(5-Bromo-3-propylisochroman-l-yl)-4,5-dihydro-lH-imidazole The title compound was prepared from l(-2-bromophenyl)pentan-2-ol (only 50% of the prepared ester was used in the last step) using the procedure of synthesis method B (Lewis acid catalyst BF3*Et 0). (Yield 400 mg). NMR (CD3OD) d ppm 7.41 - 7.54 (m, IH), 7.23 (d, IH), 7.03 - 7.14 (m, IH), 5.39 (s, IH), 3.74 (td, IH), 3.50 - 3.68 (m, 4H), 2.85 (d, IH), 2.58 (dd, IH), 1.45 - 1.75 (m, 4H), 0.92 - 1.04 (in, 3H). EXAMPLE 41: 2-(5-IsopropyIisochroman-l-yl)-4,5-dihydro-lH-imidazole To a solution of 2-(5-bromoisochroman-l-yl)-4,5-dihydro-lH-imidazole (0.25g, synthesis method A), palladium(Il) acetate (0.0 lg), tri-tert-butylphosphine (0.044 ml) and toluene (3ml) in ice bath temperature was added 6.22ml of 0.5M isopropyl zinc bromide in THF, and stirred at ambient temperature for 3 hrs. The reaction was quenched with dilute hydrochloric acid, and the organic phase was separated. The aqueous phase was made alkaline with 1M NaOH, and purified with separation methods A and G to yield the title compound. (Yield 2 mg).. Ή NMR (CDCI3) d ppm 7.20 (br s, 3H), 5.48 (s, IH), 4.22 - 4.27 ( , IH), 3.85 - 3.91 (m, IH), 3.63 (br s, 4H), 3.05 - 3.12 (m, IH), 2.91 - 2.99 (m, IH), 2.75 - 2.80 (m, IH), 1.21 - 1.23 (m, 6H). EXAMPLE 42: 2-(5-Fluoroisochroman-l-yl)-4,5-dihydro-lH-imidazole The title compound was prepared from 2-(2-fluorophenyl)ethanol (0.4g) using the procedure of synthesis method B. The final product was purified by washing the evaporation residue with cold water. (Yield 0.09g). Ή NMR (DMSO-d ) d ppm 7.17 -7.23 (m, 1H), 7.03 - 7.08 (m, 2H), 6.31 (br s, 1H), 5.32 (s, 1H), 4.10 - 4.15 (m, 1H), 3.79 - 3.85 (m, 1H), 3.43 - 3.75 (br s, 2H), 3.09 - 3.30 (br s, 2H), 2.67 - 2.83 ( , 2H). EXAMPLE 43: 2-(5-Bromo-3-ethylisochroman-l-yl)-4,5-dihydro-lH-imidazole The title compound was prepared from l-(2-bromophenyl)butan-2-ol (600 mg) using the procedure of synthesis method B (boron trifluoride diethyletherate was used instead of titanium(rV)chloride) and separation method D. (Yield 480 mg). Ή NMR (CD3OD) d ppm 7.40 - 7.53 (m, 1H), 7.24 (d, 1H), 7.09 (q, 1H), 5.39 (s, 1H), 3.52 - 3.70 (m, 5H), 2.80 - 2.92 (m, H), 2.58 (dd, IH), 1.56 - 1.80 (m, 2H), 0.99 - 1.10 (m, 3H). EXAMPLE 44: 2-((3R)-5-methoxy-3-methylisochroman-l-yi)-4,5-dihydro-lHimidazole The title compound was prepared from 2-((3/?)-5-bromo-3-methylisochroman-l-yl)-4,5-dihydro-lH-imidazole (200 mg) using the procedure of synthesis method E (with 2-di-tertbutylphosphino- 3,4,5,6-tetramethyl-2 ,4',6'-triisopropyl-l , -biphenyl) and separation methods J and G. (Yield 3 1.4 mg). NMR (CDjOD) d ppm 7.08 - 7.20 (m, IH), 6.79 - 6.85 (m, 1.7H), 6.73 - 6.75 (d, 0.3H), 5.40 (s, 0.7H), 4.07 - 4. 10 (m, 0.2H), 3.80 - 3.92 ( , 3.8H), 3.46 - 3.68 (m, 4H), 2.74 - 2.90 (m, IH), 2.28 - 2.47 (m, IH), 1.35 - 1.41 (m, 2.3H), 1.31 (d, 0.7H). EXAMPLE 45: 2-((3R)-5-ethyI-3-methylisochroman-l-yI)-4,5-dihydro-lH-imidazoIe The title compound was prepared from (R)-l-(2-ethylphenyl)propan-2-ol (2.2 g) using the procedure of synthesis method A. The intermediate (3/?)-methyl 5-ethyl-3-methylisochroman-l-carboxylate was purified with the separation method E. (Yield 146 mg). NMR (CD OD) d ppm 7.01 - 7.21 (m, 3H), 5.44 (s, H), 4.06-4. 17 (m, 0.15H), 3.77 - 3.96 (m, 0.85H), 3.49 - 3.69 (m, 4H), 2.75- 2.91 (m, IH), 2.54 - 2.69 (m, 3H), 1.26 - 1.46 (m, 3H), 1. 19 (t, 3H). EXAMPLE 45 HC salt: 2-((3R)-5-ethyl-3-methylisochroman-l-yl)-4,5-dihydro-lHimidazole hydrochloride The title compound was prepared from compound of example 45 (100 mg) as described in the example 8 (IPA, yield 7 1 mg). NMR (DMSC ) ppm 10.63 (br. s., 2H), 7.13 - 7.38 (m, 2H), 6.94 - 7. 13 (m, IH), 5;87 (br. s., IH), 3.88 (br. s., 4H), 3.61 - 3.74 (m, IH), 2.66-2.82 (m, IH), 2.42-2.65 ( , IH), 2.14-2.32 (m, 3H), 1.60 - 1.83 (m, 2H), 0.79 - 1.07 (m, 3H). EXAMPLE 45 hemifumarate salt: 2-((3R)-5-ethyl-3-methylisochroman-l-yl)-4,5-dihydro-lH-iniidazole hemifumarate The title compound was prepared from compound of example 45 (940 mg) as described in the example 8 (ethanol, yield 1. 16 g). NMR (DMSC 6) d ppm 6.97 -7.20 (m, 3H), 6.43 (s, IH), 5.59 (s, 0.7H), 5.49 (s, 0.3H), 4.04 - 4.08 ( , 0.3H), 3.80 - 3.92 (m, 0.7H), 3.59 (br. s., 4H), 3.55 (s, IH), 2.77 (m, 2H), 2.56 - 2.63 (m, IH), 1.26 - 1.37 (m, 3H), 1.15 (t, 3H). EXAMPLE 46: 2-(3-Ethyl-5-methoxyisochroman-l-yl)-4,5-dihydro-lH-imidazole The title compound was prepared from l-(2-bromophenyl)butan-2-ol (1. 1 g) using the procedure of synthesis methods B (boron trifluoride diethyletherate was used instead of titanium (rV)chloride) and E (with 2-di-tert-butylphosphino-3,4,5,6-tetramethyl-2',4',6'-triisopropyl-l , l '-biphenyl) (C-0 coupling reaction was performed to intermediate ethyl 5-bromo-3-ethylisochroman-l-carboxylate, only 60% of the prepared amount was used in this step). The C-0 coupling reaction yielded free acid which was further methylated (synthesis method A) before the final reaction step. The title compound was obtained by concentration of the reaction mixture. (Yield 186 mg). Ή NMR (CD3OD) d ppm 7.12 (t, IH), 6.82 (d, 2H), 5.38 (s, IH), 3.82 (s, 3H), 3.48 - 3.69 (m, 5H), 2.73 - 2.90 (m, 1H), 2.41 (dd, 1H), 1.70 (dt, 2H), 0.96 - 1.10 (m, 3H). EXAMPLE 47: 2-((3R)-3,5-diethylisochroman-l-yl)-4,5-dihydro-lH-imidazole Step 1: (K)-l-(2-ethyIphenyl)butan-l-ol The l-bromo-2-ethylbenzene (2.0g) was dissolved in dry THF and the mixture was cooled to -78°C. 1.6 M n-BuLi (20.26 ml) was slowly added to the reaction mixture and then the mixture was stirred at -78°C. After 1 h (/?)-(+)- 1,2-epoxybutane (1.1 g) was added in 10 ml of THF. The reaction mixture was allowed to warm to ambient temperature and then stirred over night. The reaction was quenched with ice-water and product extracted in heptanes, and finally purified by using the separation method E yielding the title compound ( 1. 1 g). Step2: 2-((3/?)-3,5-diethylisochroman-l-yl)-4,5-dihydro-lH-imidazoIe The title compound was prepared from (/?)-l-(2-ethylphenyl)butan-l-ol (1.1 g) using the procedure of synthesis method A and separation method D. (Yield 660 mg). Ή NMR (CD3OD) d pp 6.99 - 7.19 ( , 3H), 5.43 (s, 1H), 3.49 - 3.68 (m, 5H), 2.74 - 2.86 (m, 1H), 2.55 - 2.66 (m,, 3H), 1.54 - 1.79 (m, 2H), 1.19 (t, 3H), 0.95 - 1. 11 (m, 3H). EXAMPLE 48: 2-((3R)-3-ethyl-5-methylisochroman-l-yl)-4,5-dihydro-lH-imidazoIe The title compound was prepared from (i?)-l-(o-tolyl)butan-2-ol (463 mg) using the procedure of synthesis method B. Boron trifluoride diethyletherate was used instead of titanium(rV)chloride and the intermediate (3/?)-ethyl 3-ethyl-5-methylisochroman-lcarboxylate was purified using separation method E. The title compound was isolated using the separation method D with MTBE-Heptane as solvent. (Yield 287 mg). NMR (DMSO-d 6) d ppm 6.95 - 7. 2 ( , 3H), 5.98 (br s, 1H), 5.32 (s, H), 3.49 - 3.81 ( , 3H), 3.20 (br s, 2H), 2.66 (d, 1H), 2.40 - 2.47 ( , 1H), 2.19 (s, 3H), 1.54 - 1.76 (m, 2H), 0.99 (t, 3H). EXAMPLE 48 HC1 salt: 2-((3R)-3-ethyl-5-methylisochroman-l -yl)-4,5-dihydro-lHimidazole hydrochloride The title compound was prepared from compound of example 48 (100 mg) as described in the example 8 (IPA, yield 72 mg). NMR (DMSO - ) d ppm 10.60 (br. s., 2H), 7.15 - 7.28 (m, 2H), 7.03 - 7. 14 (m, 1H), 5.89 (s, 1H), 3.90 (br. s 4H), 3.08 (s, 1H), 2.82 (d, 1H), 2.55 - 2.70 (m, 3H), 1.36 (d, 3H), 1. 15 (t, 3H). EXAMPLE 48 Sulfate salt: 2-((3R)-3-ethyl-5-methylisochroman-l-yl)-4,5-dihydro-lHimidazole sulfate The title compound was prepared from compound of example 48 (1.5g) as described in the example 8 (ethanol, yield 2.0g). Ή NMR (DMSO-d ) d ppm 10.32 (s, 2H), 7.16 - 7.22 ( , 2H), 7.00 - 7.02 (m, 1H), 5.78 (s, 1H), 3.87 - 3.93 (m, 5H), 2.74 (dd, 1H), 2.50-2.59 (m, 1H), 1.66 - 1.74 (m, 2H), 1.10 (t, 3H), 1.01 (t, 3H). EXAMPLE 48 Hemifumarate salt: 2-((3R)-3-ethyl-5-methylisochroman-l-yl)-4,5-dihydro-lH-imidazole hemifumarate The title compound was prepared from compound of example 48 (100 mg) as described in the example 8 (ethanol, yield 102.3 mg). Ή NMR (DMSC 6) d ppm 7.09 - 7.19 (m, 2H), 6.99 - 7.07 (m, 1H), 6.43 (s, 1H), 5.60 (s, 0.7H), 5.50 (s, 0.3H), 4.05 - 4.08 (m, 0.3H), 3.81 - 3.92 (m, 0.7H), 3.60 (s, 4H), 2.77 (dd, 1H), 2.56 - 2.64 (m, 1H), 2.44 - 2.53 (m, 2H), 1.25 - 1.37 (m, 3H), 1.15 (t, 3H). EXAMPLE 49: 2-((3/f)-3-methyl-5-(trifluoromethoxy)isochroman-l-yl)-4,5-dihydrolH-imidazole Step 1: (R)-l-(2-(trifluoromethoxy)phenyl)propan-2-ol To a solution of trifluoromethoxybenzene (5.29 mL) and N ,N ,N',N'-tetramethylethylenediamine (5.96 mL) in tetrahydrofuran (80 mL) at -78°C was added sec-butyllithium (32 mL, 1.4 M solution) over 50 minutes. After 2 hours a cooled (-78°C) solution (/?)-(+)-propylene oxide (4.20 mL) in tetrahydrofuran (20 mL) was added over 5 minutes, followed by boron trifluoride diethyl etherate (1.89 mL) over 20 minutes. The reaction mixture was stirred at - 78°C for 2 hours after which aqueous solution of H2S0 (0.3 M, 50 mL) and water (10 mL) was added. The mixture let to warm up to room temperature after which it was extracted with diethyl ether (2 x 100 mL). The combined organic phases were washed with brine, dried with Na2S0 4 and concentrated. Evaporation residue was purified by separation method E (ethyl acetate - heptane). (Yield 1.40 g). NMR (DMSO- ) d ppm 7.24-7.44 (m, 4H), 4.67 (d, 1H), 3.80-3.92 ( , 1H), 2.74 (dd, 1H), 2.65 (dd, 1H), 1.04 (d, 3H). Step 2: 2-((3R)-3-methyl-5-(trifluoromethoxy)isochroman-l-yl)-4,5-dihydro-lHimidazole The title compound was prepared from (R )-l-(2-(trifluoromethoxy)phenyl)propan-2-ol ( 10 mg) using the procedure of synthesis method B. Boron trifluoride diethyletherate was used instead of titanium(IV)chloride. (Yield 36 mg). NMR (CD OD) d ppm 7.31 - 7.16 (m, 3H), 5.45 (s, 1H), 4.12 - 4.02 (m, 0.25H), 4.94 - 4.83 (m, 0.75H), 3.70 - 3,54 (m, 4H), 2.95 - 2.85 ( , 1H), 2.59 (dd, 0.8H), 2.48 (dd, 0.3H), 1.40 (d, 2.4H), 1.34 (d, 0.9H). EXAMPLE 50: 2-((3R)-5-fluoro-3-methylisochroman-l-yl)-4,5-dihydro-lH-imidazoIe The title compound was prepared from (/?)-l-(2-fluorophenyl)propan-2-ol (170 mg) using the procedure of synthesis method B. Boron trifluoride diethyletherate was used instead of titanium(rV)chloride. The title compound was purified by trituration of the crude product with heptanes. (Yield 67 mg). NMR (CD3OD) d ppm 7.22 - 7. 14 (m, 1H), 7.05 (d, 1H), 7.01 - 6.93 (m, 1H), 5.43 (s, lH), 4.14 - 4.04 (m, 0.1H), 3.93 - 3.83 ( , 0.9H), 3.70 - 3.52 (m, 4H), 2.93 - 2.83 ( , 1H), 2.56 (dd, 0.9H), 2.46 (dd, 0.1H), 1.40 (d, 2.6H), 1.33 (d, 0.5H). . EXAMPLE 51: 2-(5-Ethoxyisochroman-l-yl)-4,5-dihydro-lH-imidazole Step 1: 5-Ethoxyisochroman-l-carboxylic acid The mixture of ethyl 5-bromoisochroman-l-carboxylate (1.0 g, synthesis methods Al and A2), cesium carbonate (4.57 g), 3,4,7, 8-tetramethyl-l,10-phenanthroline (332 mg), copper (I) iodide (134 mg) and ethariol (lO' rnl) was heated in microwave reactor at 160°C. Methanol was evaporated and the title compound was isolated and purified with separation method B. (Yield 400 mg). Step 2: 2-(5-Ethoxyisochroman-l-yl)-4,5-dihydro-lH-imidazole The title compound was prepared from using the procedure of synthesis methods A2 and A3 and purified with separation method D (heptane). (Yield 150 g). H MR (CD OD) ppm 7.1 (t, 1H), 6.80 (t, 2H), 4.11 - 4.26 (m, 1H), 4.05 (qd, 2H), 3.79 (td, 1H), 3.51 - 3.66 ( , 4H), 2.62 - 2.91 (m, 2H), 1.40 (t, 3H). EXAMPLE 52: 2-(5-Methyl-3-(2,2,2-trinuoroethyl)isochroman-l-yl)-4,5-dihydro-lHimidazole Step 1: 4,4,4-Trifluoro-l-(o-toIyl)butan-2-ol To a mixture of 2,2,2-trifluoroethylamine hydrochloride (0.271 g) in dichloromethane / water (15 / 0.5 mL) at 0°C was added sodium nitrite (0.166 g) and the resulting yellow solution was stirred for 1 hour at 0°C. The reaction mixture was then cooled to -78°C and 2-o-tolylacetaldehyde (0.134 g) was added, followed by zirconium(IV)tetrachloride. After stirring for 2 hrs at -78°C cooling was stopped and methanol (3 mL) and saturated solution of NaHC0 3 (10 mL) were added. The mixture was extracted with dichloromethane and the extracts were dried and concentrated. Evaporation residue (194 mg) was dissolved in methanol (3 ml) and solution was cooled to 0°C. Sodium borohydride (44 mg) was added and the reaction mixture was stirred for 25 minutes. C0 3-solution (2M, 5 mL) was added to the reaction mixture, followed by water (5 mL) after 5 min and the resulting solution was extracted with EtOAc. Extracts were dried and concentrated and the residue was purified by separation method E (EtOAc/heptane). (Yield 121 mg). NMR (CDC13) d ppm 7.23 - 7.12 ( , 4H), 4.26 - 4.17 (m, 1H), 2.90 (dd, 1H), 2.80 (dd, 1H), 2.45 - 2.27 (m, 2H), 2.34 (s, 3H), 1.86 (d, 1H). Step 2 : 2-(5-Methyl-3-(2,2,2-trifluoroethyl)isochroman-l-yl)-4,5-dihydro-lH-imidazole The title compound was prepared from 4,4,4-trifluoro-l-(o-tolyl)butan-2-ol (121 mg) using the procedure of synthesis method B. Boron trifluoride diethyletherate was used instead of titanium(rV)chloride. The title compound was purified by separation method E (dichloromethane-MeOH-NH 4OH). (Yield 11 mg). Ή NMR (CD3OD) d ppm 7. 13 - 7.04 (m, 2.6H), 6.99 - 6.93 (m, 0.3H), 5.47 (s, 1H), 4.41 - 4.33 ( , 0.3H), 4.15 - 4.07 (m, 0.7H), 3.63 - 3.51 ( , 4H), 2.87 - 2.46 (m, 4H), 2.25 (s, 3H). EXAMPLE 53: 2-((35)-5-methoxy-3-methylisochroman-l-yl)-4,5-dihydro-lHimidazole The title compound was prepared from 2-((3S)-5-bromo-3-methylisochroman-l-yl)-4,5-dihydro-lH-imidazole (200 mg) using the procedure of synthesis method E (with 2-di-tertbutylphosphino- 3,4,5,6-tetramethyl-2',4 ' ,6'-triisopropyl-l , -phenyl) and separation method G. (Yield 16.3 mg). NMR (CD OD) d ppm 7.10 - 7.24 (m, 1H), 6.82 - 6.90 (m, 1.6H), 6.78 (d, 0.4H), 5.44 (s, 0.7H), 4.05 - 4.15 ( , 0.3H), 3.80 - 3.93 (m, 3.7H), 3.53 - 3.70 (m, 4H), 2.80 - 2.92 (m, 1H), 2.3 1 - 2.50 (m, 1H), 1.4] (d, 2. 1H), 1.34 (d, 0.9H). EXAMPLE 54: 2-(5-(Furan-3-yl)isochroman-l-yI)-4,5-dihydro-lH-imidazole To a mixture of 2-(2-bromoisochroman-l-yl)-4,5-dihydro-lH-imidazole (100 mg), bis(tri-tbutylphosphine) palladium (9 mg), furan-3-boronic acid (80 mg) and cesium carbonate (202 mg) was added ethylene glycol dimethyl ether (4 ml), ethanol (2 ml) and water ( 1 ml). The reaction mixture was degassed with N and heated in a microwave oven for 30 min at 100°C. The title compound was purified by applying methods J and G. (Yield 19 mg). Ή NMR (CD OD) d ppm 7.60 - 7.67 (m, lH), 7.52 - 7.60 ( , 1H), 7.10 - 7.33 (m, 3H), 6.49 - 6.70 (m, 1H), 4.18 (ddd, 1H), 3.71 - 3.84 (m, 1H), 3.55 - 3.67 (m, 4H), 2.97 - 3.19 (m, 1H), 2.64 - 2.81 (m, 1H). EXAMPLE 55: 2-(5-(Prop-l-yn-l-yl)isochroman-l-yl)-4,5-dihydro-lH-imidazoIe The title compound was prepared from 2-(2-bromoisochroman- 1-yl)-4,5-dihydro- 1Himidazole (100 mg) using the procedure of synthesis method C and separation methods F and G. (Yield 3.7 mg). NMR (CD OD) d ppm 7.27 (dd, 1H), 7. 12 (m, 2H), 5.34 (s, 0.2H), 4.22 (ddd, 1H), 3.83 (ddd, 1H), 3.59 (m, 4H), 2.94 (m, 2H), 2.07 (s, 3H). EXAMPLE 56: l-(4,5-Dihydro-lH-imidazol-2-yl)isochroman-5-carboxamide The mixture of l-(4,5-dihydro-lH-imidazol-2-yl)isochroman-5-carbonitrile (example 5, 75 mg), acetamide (39 mg), zink chloride (45 mg), THF (0.5 ml) and water (0.5 ml) was heated in a microwave reactor for 50 seconds at 320 W. The title compound was purified by applying method A. (Yield 15 mg). H MR (CDCb) d ppm 8.06 (d, 1H), 7.57 (d, 1H), 7.32 (t, lH), 5.17 (s, 1H), 4. 16 - 4.41 ( , 1H), 3.75 - 4.03 ( , 1H), 2.93 - 3.44 (m, 4H), 2.77 - 2.93 ( , 2H). EXAMPLE 57: 2-(3,7,8,9,10,10a-Hexahydro-lH-cyclohepta[de]isochromen-3-yl)-4,5-dihydro-lH-imidazo!e The title compound was prepared from (6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-yl)methanol (300 mg) using the procedure of synthesis method A and separation methods F and G. (Yield 3 mg). Ή NMR (CDCI3) d ppm 6.96 - 7.24 (m, 3H), 5.32-5.48 (m, 1H), 3.74 - 4.03 (m, 3H), 3.39 - 3.60 (m, 4H), 2.65 - 2.98 (m, 2H), 1.84 - 2.1 1 (m, 2H), 1.52 - 1.82 (m, 2H), 1.19 - 1.42 (m, 2H). EXAMPLE 58: l-(l-(4,5-Dihydro-lH-imidazol-2-yI)isochroman-5-yI)ethanol, slow eluting isomer The title compound was prepared from 2-(2-bromoisochroman-l-yl)-4,5-dihydro-lHimidazole (300 mg) using the procedure of Example 13 and purified by applying separation method G. (Yield 2 mg). Ή NMR (CD3OD) d ppm 7.48 (d, IH), 7.26 (m, 2H), 5.06 (q, 1H), 3.99 (m, 2H), 3.74 (s, 4H), 2.96 (dt, IH), 2.84 (dt, IH), 1.78 (d, 3H). EXAMPLE 59: 2-(5,7-Dimethylisochroman-l-yl)-4,5-dihydro-lH-imidazole The title compound was prepared from 2-(2,4-dimethylphenyl)ethanol (0,5 g) using the procedure of synthesis method A. The intermediate 5,7-dimethylisochroman-l-carboxylic acid was isolated using the separation method I and the intermediate methyl 5,7-dimethylisochroman -1-carboxylate was purified by separation method E. The title compound was isolated using separation method G. (Yield 27 mg ) . 'H NMR (CD OD) d ppm 8.45 (br. s., lH), 7.04 (s, 1H), 6.85 (s, 1H), 5.68 (s, IH), 4. 1 - 4.19 (m, IH), 3.87 - 4.02 ( , 5H), 2.76 - 2.88 (m, IH), 2.64 - 2.76 (m, IH), 2.20 - 2.35 (m, 6H). EXAMPLE 60: 2-(7-Bromo-5-methylisochroman-l-yl)-4,5-dihydro-lH-imidazoIe The title compound was prepared from 2-(4-bromo-2-methylphenyl)ethanol (4,5 g) using the procedure of synthesis method A (4-methylbenzenesulfonic in methanol was used in the step A2), and isolated using separation method D with MTBE-heptane as solvent. (Yield 242 mg). 1H NMR (DMSO-d6) d ppm 7.29 (s, IH), 7.20 (s, H), 6.32 (br. s., 1H), 5.28 (s, 1H), 4.09 (dt, IH), 3.82 (ddd, IH), 3.63 (dt, 2H), 3. 18 - 3.27 (m, 2H), 2.57 - 2.72 (m, 2H), 2.20 (s, 3H). EXAMPLE 61: 2-(7-Methoxy-5-methylisochroman-l-yl)-4,5-dihydro-lH-imidazole The title compound was prepared from methyl 7-methoxy-5-methylisochroman-lcarboxylate (0.25 g) using the procedure of synthesis method A3 and isolated using separation method G. (Yield 113 mg). Ή NMR (DMSO-d6) d ppm 6.65 - 6.75 (m, IH), 6.54 - 6.65 (m, IH), 6.18 (br. s IH), 5.23 (s, IH), 3.98 - 4.25 ( , IH), 3.71 - 3.86 ( , IH), 3.66 (s, 3H), 3.20 - 3.30 ( , 4H, H 0), 2!52 - 2.72 (m, 2H), 2. 17 (s, 3H). EXAMPLE 62: 2-(3,5-Di ethylisothiochron an-l -yl)-4,5-dihydro-lH-imidazole The title compound was prepared from methyl 3,5-dimethylisothiochroman-l-carboxylate (0.44 g) using the procedure of synthesis method A3 and isolated using separation method G. (Yield 10 mg). NMR (CD OD) d ppm 6.93 - 7.23 (m, 3H), 3.38 - 3.68 (m, 5H), 2.98 - 3. 19 (m, IH), 2.48 (dd, IH), 2. 19 - 2.37 (m, 3H). EXAMPLE 63: 2-(5-Bromo-3-methylisothiochroinan-l-yl)-4,5-dihydro-lH-imidazole The title compound was prepared from methyl 5-bromo-3-methylisothiochroman-lcarboxylate (0.5 g, synthesis methods Al and A2 ) using the procedure of synthesis method A3 and isolated using separation method E. (Yield 72 mg). Ή NMR (CD3OD) d ppm 7.53 (d, IH), 7.03 - 7.25 (m, 2H), 3.47 - 3.69 (m, 5H), 3.37 - 3.46 ( , IH), 2.57 (dd, IH), 1. 17 - 1.46 (m, 3H). EXAMPLE 64: 2-(5-Methylisothiochroman-l-yl)-4,5-dihydro-lH-imidazoIe The title compound was prepared from methyl 5-methyl-isothiochroman-l-carboxylate (1.3 g, synthesis method F) using the procedure of synthesis method A3 and isolated using separation method D with EtOAc/EtOH as solvents. (Yield 110 mg). NMR (CDC13) d ppm 6.90 - 7.17 (m, 3H), 4.63 (s, 1H), 3.52 - 3.75 (m, 4H), 3.08 - 3.25 (m, 1H), 2.80 - 3.02 (m, 3H). EXAMPLE 65: 2-(5-Bromoisothiochroman-l-yl)-4,5-dihydro-lH-imidazo!e Synthesis Method F Synthesis Method Fl: Methyl-2-((2-bromophenethyl)thio)acetate A mixture of methyl 2-mercaptoacetate (2.2 g), 2-bromophenethyl methanesulfonate (5.7 g), 2,3,4,6,7, 8,9, 10-octahydropyrimido[l,2-a]azepine (3.7 g) and THF (30 ml) was stirred at ambient temperature for 1.5 hrs and separation method A and E yielded the title compound (4.4 g). Synthesis Method F2: Methyl-2-((2-bromophenethyl)thio)-2-chIoroacetate A mixture of methyl 2-((2-bromophenethyl)thio)acetate (4.4 g), l-chloropyrrolidine-2,5-dione (2 g) and carbon tetrachloride (2.4 g) was stirred on ice-bath for 2.5 hrs, filtrated and evaporated to yield the title compound (4.7 g). Synthesis Method F3: Methyl-5-bromoisothiochronian-l-carboxylate A mixture of methyl 2-((2-bromophenethyl)thio)-2-chloroacetate (4.7 g), aluminum trichloride (2 g) and DCM (15 ml) was stirred in ice bath and allowed to warm up to ambient temperature and stirred 3.5 hrs. Separation method B and E yielded the title compound (2.9 g). Synthesis Method F4: 2-(5-Bromoisothiochroman-l-yl)-4,5-dihydro-lH-imidazoIe The title compound was prepared from methyl-5-bromo-isothiochroman-l-carboxylate (0.5 g) using the procedure of synthesis method A3 and isolated using separation methods E and D (2-propanol, Yield 2 1 mg). Ή NMR (DMSO- ) d ppm 7.52 (dd, 1H), 7.02 - 7. 19 (m, 2H), 4.65 (s, 1H), 3.77 (td, 1H), 3. 17 - 3.60 (br. s., 4H), 2.96 - 3.09 (m, 1H), 2.75 - 2.95 (m, 2H). EXAMPLE 66: 2-(5-Bromo-l-methylisothiochroman-l-yl)-4,5-dihydro-lH-imidazole The title compound was prepared from methyl-5-bromoisothiochroman-l-carboxylate (1.6 g) using the procedures of the synthesis method of example 1 and A3 and isolated with the separation method E. (Yield 30 mg). NMR (CDC1. d ppm 7.46-7.56 ( , 1H), 7.21-7.39 (m, 1H, CHC13), 7.02-7. 16 (m, lH), 3.17-4.0 (m, 4H), 2.70-3.10 ( , 3H), 1.48-2.01 (m, 4H). EXAMPLE 67: 2-(5,7-Dibromo-3-ethyIisochroman-l-yl)-4,5-dihydro-lH-imidazole, hydrochloride Step 1: Ethyl 5,7-dibromo-3-ethyIisochroman-l-carboxylate A dry microwave vial was charged with di^-methoxobis(l,5-cyclooctadiene)diiridium (I) (5.0 mg), 4,4'-dimethoxy-2,2'-dipyridyl (3.2 mg), bis(pinacolato)diboron (93 mg) and 2-(5-bromo-3-ethylisochroman-l-yl)-4,5-dihydro-lH-imidazole (157 mg, example 43) and the vial was flushed using vacuum/N 2 cycle for several times. Tetrahydrofuran ( 1 mL) was added and solution was heated to 80°C in a sealed vessel. After 4 hours heating was stopped and the reaction mixture was concentrated. Evaporation residue was dissolved in methanol (6 mL) and solution of CuBr2 in water (6 mL) wad added. The resulting heterogeneous mixture was heated to 80°C in sealed vessel. After 8 hours the reaction mixture was cooled to room temperature and extracted with diethyl ether. Combined organic phases were washed with brine, dried with Na S0 4 and concentrated. Evaporation residue was purified by separation method E (ethyl acetate - heptane). (Yield 94 mg). NMR (CDC ) d ppm 7.63 - 7.67 (m, 1H), 7.55 - 7.58 ( , 0.33H), 7.38 - 7.44 (m, 0.63H), 5.31-5.36 (m, 0.1 H) 5.28-5-31 (d, 0.89H), 4.19 - 4.38 (m, 2H), 4.00 - 4.09 (m, 0.37H), 3.50 - 3.60 (m, 0.63H), 2.72 - 2.83 (m, 1H), 2.56 (ddd, 0.64H), 2.39 (dd, 0.36H), 1.66 - 1.90 (m, 2H), 1.30 - 1.36 (m, 3H), .02- 1.13 (m, 3H). Step 2: 2-(5,7-Dibromo-3-ethylisochroman-l-yl)-4,5-dihydro-lH-imidazole, hydrochloride, Title compound was synthesized using synthesis method A3 and converted to HCl-salt using salt formation method A. (Yield 60 mg). H NMR (DMSO - ) ppm 10.59 (s, 1.57H), 10.08 (s, 0.36H), 7.93-7.96 ( , lH), 7.59 (d, 0.19H), 7.48 - 7.51 (m, 0.77H), 5.92 (br s, 0.19H), 5.90 (br s, 0.78H), 3.84 - 4.00 (m, 4H), 3.63-3.78 (m, 1H), 2.74-2.84 (m, 1H), 2.50-2.57 (m, 1H), 1.61 - 1.77 ( , 2H), 0.94 - 1.02 (m, 3H). EXAMPLE 68: Enantiomer of 2-5-bromo-3-(2,2,2-trifluoroethyl)isochroman-l-yl)-4,5-dihydro-lH-imidazole, HC salt Step 1: l-(2-Bromophenyl)-4,4,4-trifhiorobutan-2-one To a solution of 2,2,2-trifluoroethanamine hydrochloride (27. 1 g, 200 mmol) in DCM (400 ml) and water (50 ml) was added NaN0 2 (15.43 g, 241 mmol) at 0°C and stirred for Ih. Then cooled to 78°C then added 2-(2-bromophenyl)acetaldehyde (20 g, 100 mmol) and ZrCl (30.4 g, 130 mmol) and stirred for 2 h. The reaction mixture was quenched with MeOH (30 ml). The title compound was purified by separation methods A and E. (Yield 13.0 g). Step 2 : Enantiomer of (l-(2-bromophenyl)-4,4,4-trifluorobutan-2-ol To a solution of l-(2-bromophenyl)-4,4,4-trifluorobutan-2-one (7.0 g, 24.9 mmol) in MeOH (150 ml) was added NaBH4 (1.23 g, 32.3 mmol) at 0 °C and stirred for l h at RT. Then the reaction mixture was quenched with MeOH and concentrated under reduced pressure to afford crude compound. The title compound was purified by separation methods A, E and H. (Yield 1.6 g of Enantiomer- 1 and 1.4 g -Enantiomer-2). The enantiomer- 1 showed up at tr =5.67 min and enantiomer-2 showed up at tr =9.57 min with Chiralcel OD-H (4.6X250mm) 5m, hexane : 2-PrOH: TFA (90: 10:0. 1), 1 ml/min. Step 3 : Enantiomer of 2-5-Bromo-3-(2,2,2-trifluoroethyl)isochroman-l-yl)-4,5-dihydrolH-imidazole, HCl salt The title compound was prepared from enantiomer- of ethyl l-(2-bromophenyl)-4,4,4-trifluorobutan-2-ol (500 mg) by the synthesis method B and isolated with the separation method E. The obtained base was converted to HCl salt using salt formation method A (HCl in Et20 and DCM as solvent) (Yield 192 mg). Ή NMR (DMSO- ) 6.ppm 10.73 (br. s., 1.95H), 10.26 (br. s., 2.05H), 7.70 (overlapping dd, 2H), 7.20 - 7.42 (overlapping m, 4H), 5.99 (br. s, 1.02H), 5.98 (br. s, 0.98H), 4. 16 - 4.33 (overlapping m, 2H), 3.8 1 - 3.96 (m, 8H), 2.59 - 3.09 (m, 8H). EXAMPLE 69: 2-(5-Methoxy-l-methylisochroman-l-yl)-4,5-dihydro-lH-imidazole The solution of ethyl glyoxate (50% toluene sol, 11.66ml) and 2-methoxybenzeneethano (12.73ml) were stirred for 1 hr to yield ethyl 2-hydroxy-2-(2-methoxyphenethoxy)acetate. The formation of ethyl 2-hydroxy-2-(2-methoxyphenethoxy)acetate was detected by NMR and the reaction mixture was cooled with ice-bath and treated with pyridine (48.4ml), 4-dimethylaminopyridine (0.44g), and acetyl chloride (12.85ml). After stirring under + 7°C for 1 hr, heptane (50ml) was added, and the ice-bath cooling was removed to let the reaction mixture reach ambient temperature followed by filtration. The filtare was washed with MTBE (3 x 50ml), and the combined solvents were washed with NaHC0 (sat aq sol), water and NaCl (sat aq sol), dried over Na2S0 , and filtered. Organics were evaporated, toluene added and evaporated. By-products and residual solvents were distilled of (0 mbar-1 rhbar / 72° -105°C), and the residula was dissolved in ethyl acetate. Silica gel and active carbon were added, the solution stirred for 10 min, and filtered. Organics were evaporated to yield ethyl 2-acetoxy-2-(2-methoxyphenethoxy)acetate (12.3g) which was used in the next step. The solution of ethyl 2-acetoxyr2-(2-methoxyphenethoxy)acetate (12.3g) in dichloromethane (415ml) at -20°C was treated with A1C1 (5.5g), and stirred for 1 hr. A1C1 (5.5g) was added to the solution and stirred for 3.5 hrs, poures into ice-water (400 ml). Separation method A was applied, followed by distillation (1-2 mbar / 120-130°C) of the crude product to yield ethyl 5-methoxyisochroman-l-carboxylate (5. lg). The mixture of NaH (0.68 g), ethyl 5-methoxyisochroman-l-carboxylate (lg) and DMF (10 ml) was stirred for 2 hrs in ice-bath temperature. Iodomethane (2.6 ml) was added and the mixture was stirred at ambient temperature for 16 hrs. The intermediate ethyl 5-methoxy-lmethylisochroman-l-carboxylate (0.7g) was purified with separation method A and the title compound was synthesized using the procedure of synthesis method A step 3 and separation method D (diethyl ether). (Yield 0.1 g). NMR (DMSO-d 6) d pp 7. 10 (tr, 1H), 6.83 (dd, 2H), 6.08 (s, 1H), 3.85 (m, 2H), 3.77 (s, 3H), 3.44 - 3.70 (br m, 2H), 3.07 - 3.28 (br s, 2H), 2.62 (tr, 2H), 1.60 (s, 3H). EXAMPLE 70: 2-(5-Methoxyisothiochroman-l-yI)-4,5-dihydro-lH-imidazoIe The title compound was prepared from 2-methoxyphenethyl methanesulfonate (3.58 g) using the procedure of synthesis method F. The title compound was purified by using the separation method E. (Yield 60 mg). 1H NM (CD OD) ppm . 1 (t, 1H), 6.84 (d, 1H), 6.73 (d, 1H), 3.82 (s, 3H), 3.46 - 3.66 (m, 4H), 3.03 - 3.17 (m, 2H), 2.75 - 2.87 (m, 2H). EXAMPLE 71: 2-((3R)-5-methoxy-l,3-dimethylisochroman-l-yl)-4,5-dihydro-lHimidazole The mixture of NaH (0. 17 g), (3R)-ethyl 5-methoxy-3-methylisochroman-l-carboxylate (0.3g) and DMF (7ml) was stirred for 2 hrs in ice-bath temperature. Iodomethane (0.7 ml) was added and the mixture was stirred at ambient temperature for 6 hrs. The intermediate (3R)-ethyl 5-methoxy-l,3-dirhethylisochroman-l-carboxylate (0.4g) was purified with separation method A and the title compound was synthesized using the procedure of synthesis method A step 3 and separation method E (EtOAc/DCM/triethyl amine 10/20/1). (Yield 0.3 g). NMR (CDC13) d ppm 7.01 - 7.24 ( , 2H), 6.71 - 6.76 (m, 1H), 3.97 - 4.24 (m, 1H), 3.80 - 3.84 (m, 3H), 3.37 - 3.77 (br, 3H), 2.77 - 2.90 (m, 1H), 2.32 - 2.42 (m, 1H), 1.77 (d, 3H), 1.35 -1.41 (m, 3H), 1.24 - 1.29(m, lH). EXAMPLE 72: 2-(5-(2,2,2-Trifluoroethyl)isochroman-l-yl)-4,5-dihydro-lH-imidazole Step 1: 2-(2-(2,2,2-TrifluoroethyI)phenyl)oxirane Bromo-2-(2,2,2-trifluoroethyl)benzene (0.5 g) was dissolved in degassed toluene and tributyl(vinyl)tin (0.67 mL), Pd (dba) (0.096g) and tri-/3,5-dimethylisochroman- 1-yl)-4,5-dihydro- 1Himidazole, 2-(5-methoxy-3-methylisochiOman-l-yl)-4,5-dihydro-l H-imidazole, 2-(5^ ethyl-3-methylisochroman - l -yl)-4,5-dihydro - lH-imidazole, 2-(5-bromo-3-propylisochroman- 1-yl)-4,5-dihydro- 1H-imidazole, 2-(5-isopropylisochroman- 1-yl)- 4,5-dihydro-l H-imidazole, 2-(5-fluoroisochroman - l -yl)-4,5-dihydro - lH-imidazole, 2- (5-bromo-3-ethylisochroman- 1-yl)-4,5-dihydro- 1H-imidazole, 2-((3R)-5-methoxy-3-methylisochroman- 1-yl)-4,5-dihydro- 1H-imidazole, 2-((3/?)-5-ethyl-3-rhethylisochroman- 1-yl)-4,5-dihydro- 1H-imidazole, 2-((3/?)-5-ethyl-3-methylisochroman- l -yl)-4,5-dihydro- 1H-imidazole hydrochloride, 2-((3 )-5-ethy!-3-methylisochroman - l -yl)-4,5-dihydro- lH-imidazole hemifumarate, 2-(3-ethyl-5-methoxyisochroman - l -yl)-4,5-dihydro- lH-imidazole, 2-((3/?)-3,5-diethylisochroman - l -yl)-4,5-dihydro- lH-imidazole, 2-((3/?)-3-ethyl-5-methylisochroman - l -yl)-4,5-dihydrolH-imidazole, 2-((3R)-3-ethyl-5-methylisochroman - l -yl)-4,5-dihydro - lH-imidazole hydrochloride, 2-((3/?)-3-ethyl-5-methylisochroman - l -yl)-4,5-dihydro - lH-imidazole sulfate, 2-((3/?)-3-ethyl-5-methylisochroman - l -yl)-4,5-dihydro - lH-imidazole hemifumarate, 2-((3/?)-3-methyl-5-(trifluoromethoxy)isochroman - l -yl)-4,5-dihydro - lHimidazole, 2-((3/?)-5-fluoro-3-methylisochroman - l -yl)-4,5-dihydro - lH-imidazole, 2-(5-ethoxyisochroman - l -yI )-4,5-dihydro- lH-imidazole, 2-(5-methyl-3-(2,2,2-trifluoroethyl)isochroman - l-yl)-4,5-dihydro - lH-imidazole, 2-((35)-5-methoxy-3-methylisochroman- l -yl)-4,5-dihydro- 1H-imidazole, 2-(5-(furan-3-yl)isochroman- 1-yl)- 4,5-dihydro- 1H-imidazole, 2-(5-(prop- -yn- 1-yl)isochroman- 1-yl)-4,5-dihydro- 1Himidazole, l-(4,5-dihydro- lH-imidazol-2-yl)isochroman-5-carboxarnide, 2- (3,7,8,9, 10,lOa-hexahydro- 1H-cyclohepta[de]isochromen-3-yl)-4,5-dihydro- 1Himidazole, slower eluting isomer of l-(l-(4,5-dihydro-lH-imidazol-2-yl)isochroman-5-yl)ethanol, 2-(5,7-dimethylisochroman-l-yl)-4,5-dihydro-l H-imidazole, 2-(7-bromo-5-methylisochroman-l-yl)-4,5-dihydro-l H-imidazole, 2-(7-methoxy-5-methylisochroman- 1-yl)-4,5-dihydro- 1H-imidazole, 2-(3,5-dimethylisothiochrornan- 1-yl)-4,5-dihydro-l H-imidazole, 2-(5-bromo-3-methylisothiochroman-l-yl)-4,5-dihydro- 1H-imidazole, 2-(5-methylisothiochroman-l-yl)-4,5-dihydro-l H-imidazole, 2-(5-bromoisothiochroman- -yl)-4,5-dihydro- 1H-imidazole, 2-(5-bromo- 1-methylisothiochroman- 1-yl)-4,5-dihydro- H-imidazole, 2-(5,7-dibromo-3-ethylisochroman-l-yI)-4,5-dihydro-l H-imidazole hydrochloride, enantiomer of 2-5-bromo-3-(2,2,2-trifluoroethyl)isochroman-l-yl)-4,5-dihydro-l H-imidazole hydrochloride, 2-(5-methoxy- 1-methylisochroman- 1-yl)-4,5-dihydro- 1H-imidazole, 2- (5-methoxyisothiochroman- 1-yl)-4,5-dihydro- H-imidazole, 2-((37?)-5-methoxy- 1,3-dimethylisochroman- 1-yl)-4,5-dihydro- 1H-imidazole, 2-(5-(2,2,2-trifluoroethyl)isochroman- 1-yl)-4,5-dihydro- 1H-imidazole, 2-((3R)-5-ethyl- 1,3-dimethylisochroman-l-yl)-4,5-dihydro-l H-imidazole, 2-(5-methyl-3- (methoxymethyl)isochromah- 1-yl)-4,5-dihydro- 1H-imidazole, 1-(4,5-dihydro- 1Himidazol- 2-yl)-5-methylisochroman-7-ol hydrobromide, 1-(4,5-dihydro- 1H-imidazol-2-yl)-3-ethylisochroman-5-ol hydrochloride, enantiomer-2 of 2-(5-methoxy-3-(2,2,2-trifluoroethyl)methylisochroman- 1-yl)-4,5-dihydro- 1H-imidazole, 2-( 1,5-dimethylisothiochroman-l-yl)-4,5-dihydro-l H-imidazole, 2-(5- (trifluoromethoxy)isochroman-l-yl)-4,5-dihydro-l H-imidazole hydrochloride, enantiomer- 1of 2-(3-ethylisochroman-l-yl)-4,5-dihydro-l H-imidazole hydrochloride, 2-(3-(2-fluoroethyl)-5-methylisochroman-l-yl)-4,5-dihydro-l H-imidazole hydrochloride, enantiomer of 2-(5-methoxyisochroman- 1-yl)-4,5-dihydro- 1Himidazole, enantiomer-2 of 2-5-bromo-3-(2,2,2-trifluoroethyl)isochroman-l-yl)-4,5-dihydro- H-imidazole hydrochloride, 2-(3-(2,2-difluoroethyl)-5-methylisochroman- -yl)-4,5-dihydro-l H-imidazole hydrochloride, 2-(7-methoxy-3,5-dimethylisochroman-lyl)- 4,5-dihydro-l H-imidazole, enantiomer-2 of 2-((3)-5-methyl-3-(2,2,2-trifluoroethyl)isochroman- 1-yl)-4,5-dihydro- 1H-imidazole hydrochloride, 2-(5- (methylthio)isochroman- 1-yl)-4,5-dihydro- H-imidazole, enantiomer-2 of 2-((3)-5-bromo-3-propylisochroman- 1-yl)-4,5-dihydro- 1H-imidazole hydrochloride, enantiomer2 of 2-((3R)-3-(2,2-difluoroethyl)-5-methylisochroman-l-yl)-4,5-dihydro-lH-imidazole hydrochloride, 2-(5-(difluoromethoxy)isochroman-l-yl)-4,5-dihydro-lH-imidazole hydrochloride, 2-((3/?)-3-ethyl-5-methoxyisochroman-l-yl)-4,5-dihydro-lH-imidazole, enantiomer-1 of 2-(5-chloroisochroman-l-yl)-4,5-dihydro-lH-imidazole hydrochloride, 2-((3/?)-5-(difluoromethoxy)-3-methylisochroman-l-yl)-4,5-dihydro-lH-imidazole hydrochloride, enantiomer of 2-(5-bromo-3-ethylisochroman-l-yl)-4,5-dihydro-lHimidazole, enantiomer-1 of 2-(5-chloroisochroman-l-yl)-4,5-dihydro-lH-imidazole hydrochloride, enantiomer-2 of 2-(3-ethylisochroman-l-yl)-4,5-dihydro-lH-imidazole, enantiomer-2 of 2-(5-methoxyoisochroman- -yl)-4,5-dihydro- 1H-imidazole hydrochloride, 2-(l -methyl- l,3-dihydr0benzo[de]isochromen-l-yl)-4,5-dihydro-lHimidazole, 2-(5-(difluoromethyl)isochroman-l-yl)-4,5-dihydro-l H-imidazole hydrochloride, enantiomer-2 of 2-(5-chloroisochroman-l-yl)-4,5-dihydro-l H-imidazole hydrochloride, enantiomer-2 of 2-(5-bromoisochroman-l-yl)-4,5-dihydro-l H-imidazole hydrochloride, 2-( 1,3-dihydrobenzo[de]isochromen- -yl)-4,5-dihydro- 1H-imidazole hydrochloride, enatiomer of 2-(l -methyl- l ,3-dihydrobenzo[de]isochromen-l-yl)-4,5-dihydro- 1H-imidazole, 2-(3-methyl- 1,3-dihydrobenzo[de]isochromen- 1-yl)-4,5-dihydro- 1H-imidazole hydrochloride, 2-(3-ethyl- 1,3-dihydrobenzo[de]isochromen- 1-yl)-4,5-dihydro-l H-imidazole hydrochloride, or enantiomer of 2-(5-bromo-lmethylisochroman- 1-yl)-4,5-dihydro- H-imidazOle 8 . The compound according to any one of claims 1 to 7 for use as a medicament. 9. The compound according to any one of claims 1 to 8 for use in the treatment of disorder, condition or disease where an alpha2 agonist is indicated to be useful. 10. The compound according to any one of claims 1 to 8 for use in the treatment of a disorder, condition or disease where an alpha2A agonist is indicated to be useful. 11. The compound according to claim 10, wherein the disorder, condition or disease is delirium, hyperactive delirium, insomnia, ADHD, benzodiazepine or alcohol or opioid or tobacco withdrawal, premature ejaculation, hypertension, tachycardia, restless leg syndrome, muscular spasticity, hot flashes, anxiety, post traumatic stress disorder, pain, chronic pelvic pain syndrome, breakthrough cancer pain, or condition wherein sedation or analgesia is needed. 12. A method for the treatment of a disorder, condition or disease where an alpha2 agonist is indicated to be useful, which method comprises administering to a mammal in need of such treatment an effective amount of at least one compound according to claim 1. 13. A method for the treatment of a disorder, condition or disease where an alpha2A agonist is indicated to be useful, which method comprises administering to a mammal in need of such treatment an effective amount of at least one compound according to claim . 14. The method according to claim 13, wherein the disorder, condition or disease is delirium, hyperactive delirium, insomnia, ADHD, benzodiazepine or alcohol or opioid or tobacco withdrawal, premature ejaculation, hypertension, tachycardia, restless leg syndrome, muscular spasticity, hot flashes, anxiety, post traumatic stress disorder, pain, chronic pelvic pain syndrome, breakthrough cancer pain, or condition wherein sedation or analgesia is needed. 15. A pharmaceutical composition comprising at least one compound according to any one of claims 1 to 7 and a pharmaceutically acceptable carrier, diluent and/or excipient. 16. The pharmaceutical composition according to claim 15, wherein the composition further comprises at least one other active ingredient.