RU2642466C2 - Multifunctional quinoline derivatives as antineurodegenerative agents - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to a hydroxy-derived quinoline of the formula (I)

or to a pharmaceutically acceptable salt thereof, (I) wherein R¹ is hydrogen, (C₁-C₃)alkyl, (C₁)alkylene(C₃)cycloalkyl, (C₁)haloalkyl or (C₁)alkylene(C₆)aryl; R² is hydrogen or halogen; R³ is hydrogen, halogen, (C₁)alkyl or (C₁)alkoxy; R⁴ is hydrogen, halogen, (C₁)alkyl, (C₁)alkoxy or (C₁)haloalkyl; R⁵ and R⁶ are hydrogen; and R⁷ is (C₉-C₁₅)alkanol, (C₁)alkylenepiperazinyl(C₁-C₂)alkanol, (C₁-C₈)alkylenepiperazinyl (C₁-C₂)alkyl, (C₁₀-C₁₃)alkylene OCOCH₃, (C₁)alkylene(C₁)alkylamino(C₃)alkynyl, (C₁)alkyleneamino(C₈)alkanol or (C₁)alkyleneamino(C₆)alkanol(C₁)alkylene(8-methoxyquinolin-2-yl); or (II), where R¹, R², R³, R⁴ and R⁶ each is as described in (I) above; R⁵ is (C₁₁-C₁₂)alkanol, and R⁷ is hydrogen. The invention also relates to a pharmaceutical composition based on the formula (I) compounds, a method for treatment of Alzheimer's disease, traumatic brain injury and/or damage to the spinal cord and a method for improvement of the ability of learning and/or memory in a patient suffering from Alzheimer's disease, based on the formula (I) compound.

EFFECT: new hydroxy derivatives of quinoline have been obtained that have useful biological properties.

13 cl, 13 dwg, 9 ex

Description

BACKGROUND

US Pat. Nos. 7,439,243 and 7,452,888 describe a number of quinoline derivatives that are useful in treating CNS disorders, including Alzheimer's disease. US Pat. No. 7,090,053 describes a number of quinoline derivatives that are suitable for treating Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, stroke, ischemia, traumatic brain damage, spinal cord injury, or osteoarthritis.

SUMMARY OF THE INVENTION

In one aspect, the present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt, solvate or hydrate, prodrug or metabolite thereof

where R ¹ represents hydrogen, (C ₁ -C ₈ ) alkyl, (C ₁ -C ₈ ) alkylene (C ₃ -C ₈ ) cycloalkyl, (C ₁ -C ₈ ) haloalkyl or (C ₁ -C ₈ ) alkylene (C ₆ -C ₂₀ ) aryl;

R ² represents hydrogen or halogen;

R ³ represents hydrogen, halogen, (C ₁ -C ₈ ) alkyl or (C ₁ -C ₈ ) alkoxy;

R ⁴ represents hydrogen, halogen, (C ₁ -C ₈ ) alkyl, (C ₁ -C ₈ ) alkoxy or (C ₁ -C ₈ ) haloalkyl;

R ⁵ represents hydrogen or (C ₁ -C ₂₀ ) alkanol;

R ⁶ represents hydrogen; and

R ⁷ represents hydrogen, (C ₁ -C ₂₀ ) alkanol, (C ₁ -C ₈ ) alkylene (C ₃ -C ₈ ) heterocyclyl (C ₁ -C ₂₀ ) alkanol, (C ₁ -C ₈ ) alkylene (C ₃ -C ₈ ) heterocyclyl (C ₁ -C ₂₀ ) alkyl, (C ₁ -C ₈ ) alkylene (C ₁ -C ₆ ) alkylamino (C ₁ -C ₆ ) alkynyl, (C ₁ -C ₈ ) alkyleneamino (C ₁ -C ₂₀ ) alkanol or (C ₁ -C ₈ ) alkyleneamino (C ₁ -C ₂₀ ) alkanol (C ₁ -C ₈ ) alkylene-substituted (C ₃ -C ₂₀ ) heteroaryl.

In another aspect, the present invention relates to a method for producing the above compounds, the method comprising:

(1) reacting a compound of formula (II)

where R ² , R ³ , R ⁴ , R ⁵ and R ⁶ each independently represents hydrogen; or

R ² , R ⁴ , R ⁵ and R ⁶ each independently represents hydrogen, and R ³ represents CH ₃ ; or

R ² , R ³ , R ⁵ and R ⁶ each independently represents hydrogen, and R ⁴ represents CH ₃ , F, Cl or Br; or

R ² , R ⁵ R ⁶ each independently represents hydrogen, R represents OCH ₃ , and R ⁴ represents Cl; or

R ² , R ⁴ represents Cl, and R ³ , R ⁵ , R ⁶ each independently represents hydrogen,

with benzyl bromide, methyl iodide, ethyl iodide, 2-bromopropane or methylene cyclopropyl bromide in an alkaline solution at a temperature of from about room temperature to about 80 ° C to obtain a compound of formula (III)

where R ¹ represents CH ₃ , CH ₂ CH ₃ , CH (CH ₃ ) ₂ , CH ₂ CH (CH ₃ ) ₂ or benzyl; and

R ² , R ³ , R ⁴ , R ⁵ and R ⁶ each independently represents hydrogen; or

R ² , R ⁴ , R ⁵ and R ⁶ each independently represents hydrogen, and R ³ represents CH ₃ ; or

R ² , R ³ , R ⁵ and R ⁶ each independently represents hydrogen, and R ⁴ represents CH ₃ , F, Cl or Br; or

R ² , R ⁵ , R ⁶ each independently represents hydrogen, R ³ represents OCH ₃ , and R ⁴ represents Cl; or

R ² , R ⁴ represents Cl, and R ³ , R ⁵ , R ⁶ each independently represents hydrogen;

(2) reacting a compound of formula (III) with lithium bis (trimethylsilyl) amide and bromine (C ₁ C ₂₀ ) alkanol in tetrahydrofuran at 0 ° C to obtain a compound of formula (I)

where R ¹ represents CH ₃ , CH ₂ CH ₃ , CH (CH ₃ ) ₂ , CH ₂ CH (CH ₃ ) ₂ or benzyl;

R ² , R ³ , R ⁴ , R ⁵ and R ⁶ each independently represents hydrogen; or

R ² , R ⁴ , R ⁵ and R ⁶ each independently represents hydrogen, and R ³ represents CH ₃ ; or

R ² , R ³ , R ⁵ and R ⁶ each independently represents hydrogen, and R ⁴ represents CH ₃ , F, Cl or Br; or

R ² , R ⁵ , R ⁶ each independently represents hydrogen, R ³ represents OCH ₃ , and R ⁴ represents Cl; or R ³ represents Cl, and R ⁴ represents OCH ₃ , or

R ² , R ⁴ represents Cl, and R ³ , R ⁵ , R ⁶ each independently represents hydrogen; and

R ⁷ represents (CH ₂ ) ₉ OH, (CH ₂ ) ₁₀ OH, (CH ₂ ) ₁₁ OH, (CH ₂ ) ₁₂ OH, (CH ₂ ) ₁₃ OH, (CH ₂ ) ₁₅ OH,

(3) reacting a compound of formula (I), where R ¹ is benzyl with hydrogen gas under pressure in the presence of palladium on carbon at room temperature in methanol or in the presence of boron trichloride in dichloromethane at 0 ° C to obtain a compound of formula (I )

R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ each independently represents hydrogen; or

R ¹ , R ² , R ⁴ , R ⁵ and R ⁶ each independently represents hydrogen, and R ³ represents CH ₃ ; or

R ¹ , R ² , R ³ , R ⁵ and R ⁶ each independently represents hydrogen, and R ⁴ represents CH ₃ , F, Cl or Br; or

R ¹ , R ² , R ⁵ , R ⁶ each independently represents hydrogen, R ³ represents OCH ₃ , and R ⁴ represents Cl; or

R ² , R ⁴ represents Cl, and R ¹ , R ³ , R ⁵ , R ⁶ each independently represents hydrogen; and

R ⁷ represents (CH ₂ ) ₉ OH, (CH ₂ ) ₁₀ OH, (CH ₂ ) ₁₁ OH, (CH ₂ ) ₁₂ OH, (CH ₂ ) ₁₃ OH, (CH ₂ ) ₁₅ OH; or

(4) reacting a compound of formula (I), where R ¹ , R ² , R ³ , R ⁴ each independently represents hydrogen, and R ⁷ represents (CH ₂ ) ₁₁ OH, with N-chlorosuccinimide in methylene chloride at room temperature to obtain a compound of formula (I), where R ¹ , R ³ , R ⁵ and R ⁶ each independently represents hydrogen, R ² and R ⁴ each independently represents chlorine, and R ⁷ represents (CH ₂ ) ₁₁ HE ; or

(5) reacting a compound of formula (I), wherein R ¹ is methyl, R ² , R ³ , R ⁴ , R ⁵ and R ^{6 are} each independently hydrogen, and R ⁷ is (CH ₂ ) ₁₁ OH , (CH ₂ ) ₁₂ OH or (CH ₂ ) ₁₃ OH, with concentrated hydrochloric acid, ICl ₃ and glacial acetic acid to give a compound of formula (I), wherein R ¹ is methyl, R ² , R ³ , R ⁵ and R ⁶ each independently represents hydrogen, R ⁴ represents Cl, and R ⁷ represents (CH ₂ ) ₁₀ OH, (CH ₂ ) ₁₁ OH, (CH ₂ ) ₁₂ OH, (CH ₂ ) ₁₃ OH, (CH ₂ ) ₁₅ OH, (CH ₂ ) ₁₀ OCOCH ₃ , (CH ₂ ) ₁₁ OCOCH ₃ , (CH ₂ ) ₁₂ OCOCH ₃ , (CH ₂ ) ₁₃ OC OCH ₃ ; or

(6) reacting 2-aminophenol with methyl vinyl ketone in hydrochloric acid to give a compound of formula (INT-1)

(7) reacting a compound of formula (INT-1) with methyl iodide, ethyl iodide, 2-bromopropane, methylene cyclopropyl bromide or 5 benzyl bromide in an alkaline solution to obtain a compound of formula (III),

where R ¹⁰ represents methyl, ethyl, 2-propyl, methylene cyclopropyl or benzyl;

(8) reacting a compound of formula (III), wherein R ¹⁰ is methyl, ethyl, 2-propyl, methylene cyclopropyl or benzyl, with lithium bis (trimethylsilyl) amide and 10-bromo-1-decanol or 11-bromo-1 -undecanol in tetrahydrofuran at 0 ° C to give a compound of formula (I), wherein R ¹ is methyl, ethyl, 2-propyl, methylene cyclopropyl or benzyl; R ² , R ³ , R ⁴ , R ⁶ and R ⁷ each independently represents hydrogen; and R ⁵ represents (CH ₂ ) ₁₁ OH or (CH ₂ ) ₁₂ OH;

(9) reacting a compound of formula (I), wherein R ¹ is benzyl; R ² , R ³ , R ⁴ , R ⁶ and R ⁷ each independently represents hydrogen; and R is (CH ₂ ) ₁₁ OH or (CH ₂ ) ₁₂ OH, with gaseous hydrogen under pressure in the presence of palladium on carbon at room temperature in methanol to give a compound of formula (I), wherein R ¹ is hydrogen; R ² , R ³ , R ⁴ , R ⁶ and R ⁷ each independently represents hydrogen; and R ⁵ represents (CH ₂ ) ₁₁ OH or (CH ₂ ) ₁₂ OH; or

(10) reacting 2-trifluoromethoxyaniline with crotonaldehyde to give 2-methyl-8-trifluoromethoxyquinoline, which is treated with lithium bis (trimethylsilyl) amide and bromine (C ₁ C ₂₀ ) alkanol in tetrahydrofuran at 0 ° C to give a compound of formula ( I), where R ¹ represents trifluoromethyl; R ² , R ³ , R ⁴ , R ⁵ and R ⁷ each independently represents hydrogen; and R ⁷ represents (CH ₂ ) ₁₀ OH, (CH ₂ ) ₁₁ OH, (CH ₂ ) ₁₂ OH, (CH ₂ ) ₁₃ OH or (CH ₂ ) ₁₅ OH; or

(11) reacting an 8-hydroxy-2-methylquinoline compound of formula (IV), wherein R ¹ is hydrogen, methyl, ethyl, 2-propyl or methylene cyclopropyl,

with selenium dioxide in dioxane at an elevated temperature to give a compound of formula (VI), R ¹ represents hydrogen, methyl, ethyl, 2-propyl or methylenecyclopropyl.

(12) reacting a compound of formula (VI), where R ¹ is hydrogen, methyl, ethyl, 2-propyl or methylenecyclopropyl, with N-methylpropargylamine to obtain a compound of formula (I), where R ¹ is hydrogen, CH ₃ , CH ₂ CH ₃ , CH ₂ CH (CH ₃ ) ₂ , CH ₂ CH (CH ₂ ) ₂ or CH (CH ₃ ) ₂ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ each independently represents hydrogen ; and R ⁷ represents CH ₂ N (CH ₃ ) CH ₂ C = CH; or

(13) reacting a compound of formula (VI), R ¹ represents hydrogen, methyl, ethyl, 2-propyl or methylenecyclopropyl, with 2 (piperazin-1-yl) ethanol to give a compound of formula (I), where R ¹ represents hydrogen, CH ₃ , CH ₂ CH ₃ , CH ₂ CH (CH ₃ ) ₂ , CH ₂ CH (CH ₂ ) ₂ or CH (CH ₃ ) ₂ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ each independently represents hydrogen; and R ⁷ represents CH ₂ (N (CH ₂ CH ₂ ) ₂ N) CH ₂ CH ₂ OH; or

(14) reacting a compound of formula (VI) with amino (C ₁ -C ₂₀ ) alkanol to give a compound of formula (I), wherein R ¹ is hydrogen, CH ₃ , CH ₂ CH ₃ , CH ₂ CH (CH ₃ ) ₂ , CH ₂ CH (CH ₂ ) ₂ or CH (CH ₃ ) ₂ ; R ² , R ³ , R ⁴ , R ⁵ and R ⁶ each independently represents hydrogen; and R ⁷ represents CH ₂ NH (CH ₂ ) ₈ OH or CH ₂ N ((CH ₂ ) ₆ OH) CH ₂ (8-methoxyquinolin-2-yl).

In another aspect, the present invention relates to a composition comprising a therapeutically effective amount of the aforementioned compound or a pharmaceutically acceptable salt, solvate or hydrate, prodrug or metabolite thereof, and a pharmaceutically acceptable diluent or carrier.

Also in another aspect, the present invention relates to a composition comprising the aforementioned compound or a pharmaceutically acceptable salt, solvate or hydrate thereof, prodrug or metabolite and a pharmaceutically acceptable diluent or carrier, for use in treating a neurodegenerative disease.

Also in another aspect, the present invention relates to the use of the aforementioned compound for the manufacture of a medicament for the treatment of a neurodegenerative disease. In one embodiment, the medicament is a medicament for treating Alzheimer's disease.

These and other aspects will become apparent from the following description of a preferred embodiment in conjunction with the following drawings, although variations and modifications may be made therein without departing from the spirit and scope of the new concepts of the present invention.

The accompanying drawings illustrate one or more embodiments of the present invention and, together with this description, serve to explain the principles of the present invention. Where possible, the same reference numbers are used throughout the drawings to refer to the same or similar elements of an embodiment.

BRIEF DESCRIPTION OF THE DRAWINGS

In FIG. 1A-B, a morphological analysis of the effects of compound C12 on the formation of β-amyloid fibrils and the destruction of β-amyloid fibrils in the presence or absence of zinc ions is presented.

In FIG. Figure 2 shows compound C12 inhibiting the polymerization of β-amyloid in the absence of zinc ions.

In FIG. 3A-B shows compound C12 acting as a neuroprotective agent directed to β-amyloid fibrils.

In FIG. 4 shows axon growth induced by quinoline derivatives.

In FIG. 5 shows the expression of GAP43 (a marker of axonal proliferation), increased due to quinoline derivatives.

In FIG. 6 shows the results of a test on a rotating rod.

In FIG. 7A-D show Morris water maze test results.

In FIG. Figure 8 shows an increase in GAP43 and a decrease in β-amyloid fibrils in memory deficient mice affected by β-amyloid fibrils after treatment with compound C12.

DETAILED DESCRIPTION OF THE INVENTION

Singular forms include plural references unless the context clearly dictates otherwise.

A dash ("-") that is not between two letters or characters is used to indicate the attachment point for a fragment or substituent. For example, a fragment

—CONH _{2 is} attached via a carbon atom.

The term "amino" refers to -ΝΗ ₂ . An amino group may be optionally substituted as indicated herein for the term “substituted”. The term “alkylamino” refers to —NR ₂ where at least one R is alkyl and the second R is alkyl or hydrogen. The term “acylamino” refers to N (R) C (═O) R, wherein each R independently represents hydrogen, alkyl or aryl.

The term “alkyl” refers to a C ₁ -C ₁₈ hydrocarbon containing normal, secondary, tertiary or cyclic carbon atoms. Examples are methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 2-methyl-1-propyl (isobutyl, -CH ₂ CH (CH ₃ ) ₂ ), 2-butyl (sec-butyl, -CH (CH ₃ ) CH ₂ CH ₃ ), 2-methyl-2-propyl (tert-butyl, -C (CH ₃ ) ₃ ), 1-pentyl, 2-pentyl, 3-pentyl, 2-methyl-2-butyl , 3-methyl-2-butyl, 3-methyl-1-butyl, 2-methyl-1-butyl, 1-hexyl, 2-hexyl, 3-hexyl, 2-methyl-2-pentyl, 3-methyl-2 pentyl, 4-methyl-2-pentyl, 3-methyl-3-pentyl, 2-methyl-3-pentyl, 2,3-dimethyl-2-butyl, 3,3-dimethyl-2-butyl. Alkyl may be a monovalent hydrocarbon radical, as described and shown in the example above, or it may be a divalent hydrocarbon radical (eg, alkylene). Alkyl may optionally be substituted with one or more alkoxy, halo, haloalkyl, hydroxy, hydroxyalkyl, aryl, heteroaryl, heterocycle, cycloalkyl, alkanoyl, alkoxycarbonyl, amino, imino, alkylamino, acylamino, nitro, trifluoromethyl, trifluoromethoxy, carboxy, thioxo, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, acetamido, acetoxy, acetyl, benzamido, benzenesulfinyl, benzenesulfonamido, benzenesulfonyl, benzenesulfonylamino, benzoyl, benzoylamino, benzoyloxy, benzyl, benzoyloxy benzyloxycarbonyl, benzylthio, carbamoyl, carbamate, isocyanato, sulfamoyl, sulfinamoyl, sulfino, sulfo, sulfoamino, thiosulfo, NR ^x R ^y and / or COOR ^x , each of R ^x and R ^y independently being H, alkyl, alkenyl, aryl , heteroaryl, heterocycle, cycloalkyl or hydroxy. Alkyl may optionally be interrupted by one or more non-peroxy hydroxy (-O-), thio (-S-), amino (-N (H) -), methylenedioxy (-OCH ₂ O-), carbonyl (-C (= O) -), carboxy (-C (= O) O-), carbonyldioxy (-OC (= O) O-), carboxylato (-OC (= O) -), imine (C = NH), sulfinyl (SO) or sulfonyl (SO ₂ ). In addition, alkyl may optionally be at least partially unsaturated, thereby forming alkenyl.

The term "alkylene" refers to a saturated, straight or branched chain or cyclic hydrocarbon radical having 1-18 carbon atoms and having two monovalent radical centers obtained by removing two hydrogen atoms from the same or different carbon atoms of the starting alkane. Common alkylene radicals include, but are not limited to: methylene (-CH ₂ -) 1,2-ethylene (-CH ₂ CH ₂ -), 1,3-propylene (-CH ₂ CH ₂ CH ₂ -), 1,4 -butylene (-CH ₂ CH ₂ CH ₂ CH ₂ -) and the like. Alkylene may optionally be substituted with one or more alkoxy, halo, haloalkyl, hydroxy, hydroxyalkyl, aryl, heteroaryl, heterocycle, cycloalkyl, alkanoyl, alkoxycarbonyl, amino, imino, alkylamino, acylamino, nitro, trifluoromethyl, trifluoromethoxy, carboxy, thioxo, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, acetamido, acetoxy, acetyl, benzamido, benzenesulfinyl, benzenesulfonamido, benzenesulfonyl, benzenesulfonylamino, benzoyl, benzoylamino, benzoyloxy, benzyl, benzoyloxy and, benzyloxycarbonyl, benzylthio, carbamoyl, carbamate, isocyanato, sulfamoyl, sulfinamoyl, sulfino, sulfo, sulfoamino, thiosulfo, NR ^x R ^y and / or COOR ^x , each of R ^x and R ^y independently being H, alkyl, alkenyl , aryl, heteroaryl, heterocycle, cycloalkyl or hydroxy. In addition, alkylene may optionally be interrupted by one or more non-peroxy hydroxy (-O-), thio (-S-), amino (-N (H) -), methylenedioxy (-OCH ₂ O-), carbonyl (-C ( = O) -), carboxy (-C (= O) O-), carbonyldioxy (-OC (= O) O-), carboxylato (-OC (= O) -), imine (C = NH), sulfinyl ( SO) or sulfonyl (SO ₂ ). Moreover, alkylene may optionally be at least partially unsaturated, thereby forming alkenylene.

The term "alkynyl" refers to a single radical branched or unbranched hydrocarbon chain having a point of complete unsaturation (for example, carbon-carbon, sp triple bond). In one embodiment, the alkynyl group may have from 2 to 10 carbon atoms or from 2 to 6 carbon atoms. In another embodiment, the alkynyl group may have from 2 to 4 carbon atoms. Examples of groups are provided for the term, such as ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl

3-butynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 1-octynyl and the like. Alkynyl may be unsubstituted or substituted.

The term “alkoxy” refers to an alkyl-O— group wherein alkyl is defined herein. Preferred alkoxy groups include, for example, methoxy, ethoxy, p-propoxy, iso-propoxy, p-butoxy, tert-butoxy, sec-butoxy, p-pentoxy, p-hexoxy, 1,2-dimethylbutoxy and the like. Alkoxy may optionally be substituted with one or more halo, haloalkyl, hydroxy, hydroxyalkyl, aryl, heteroaryl, heterocycle, cycloalkyl, alkanoyl, alkoxycarbonyl, amino, imino, alkylamino, acylamino, nitro, trifluoromethyl, trifluoromethoxy, carboxyloxy, carboxyloxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, acetamido, acetoxy, acetyl, benzamido, benzenesulfinyl, benzenesulfonamido, benzenesulfonyl, benzenesulfonylamino, benzoyl, benzoylamino, benzoyloxy, benzyl, benzyloxy, benzyl, hydroxycarbonyl, benzylthio, carbamoyl, carbamate, isocyanato, sulfamoyl, sulfinamoyl, sulfino, sulfo, sulfoamino, thiosulfo, NR ^x R ^y and / or COOR ^x , each of R ^x and R ^y independently being H, alkyl, alkenyl, aryl , heteroaryl, heterocycle, cycloalkyl or hydroxy.

The term "alkanol" refers to a compound of the general formula ROH, where R is alkyl, as defined herein.

The term “aryl” refers to an unsaturated aromatic carbocyclic group having from 6 to 20 carbon atoms, having one ring (eg, phenyl) or several fused (jointed) rings, where at least one ring is aromatic (eg, naphthyl, dihydrophenanthrenyl, fluorenyl or antryl). Preferred aryls include phenyl, naphthyl and the like. Aryl may optionally be a divalent radical, thus forming arylene. Aryl may optionally be substituted with one or more alkyl, alkenyl, alkoxy, halo, haloalkyl, hydroxy, hydroxyalkyl, aryl, heteroaryl, heterocycle, cycloalkyl, alkanoyl, alkoxycarbonyl, amino, imino, alkylamino, acylamino, nitro, trifluoromethyl, carboxyalkyl, keto, thioxo, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, acetamido, acetoxy, acetyl, benzamido, benzenesulfinyl, benzenesulfonamido, benzenesulfonyl, benzenesulfonylamino, benzoyl, benzoylamino, zyl, benzyloxy, benzyloxycarbonyl, benzylthio, carbamoyl, carbamate, isocyanato, sulfamoyl, sulfinamoyl, sulfino, sulfo, sulfoamino, thiosulfo, NR ^x R ^y and / or COOR ^x , each of R ^x and R ^y independently being H, alkyl , alkenyl, aryl, heteroaryl, heterocycle, cycloalkyl or hydroxy.

The terms “aryloxy” and “arylalkoxy” refer respectively to an aryl group attached to an oxygen atom and an aralkyl group linked to an oxygen atom in an alkyl moiety. Examples include, but are not limited to, phenoxy, naphthyl oxy, and benzyloxy.

The term “carbocycle” refers to a saturated, unsaturated, or aromatic ring having from 3 to 8 carbon atoms as a monocycle, from 7 to 12 carbon atoms as a cyclic, and not more than about 30 carbon atoms as a polycycle. Monocyclic carbocycles usually have 3 to 6 atoms in the ring, more often usually 5 to 6 atoms in the ring. Bicyclic carbocycles have from 7 to 12 atoms in the ring, for example, located as a bicyclic [4,5], [5,5], [5,6] or [6,6] system, or from 9 to 10 atoms in the ring, located as a bicyclic [5,6] or [6,6] system. Examples of carbocycles include cyclopropyl, cyclobutyl, cyclopentyl, 1-cyclopent-1-enyl, 1-cyclopent-2-enyl, 1-cyclopent-3-enyl, cyclohexyl, 1-cyclohex-1-enyl, 1-cyclohex-2-enyl , 1-Cyclohex-3-enyl, phenyl, spirit and naphthyl. A carbocycle may optionally be substituted as described above for alkyl groups.

If a substituent is defined as an atom or atoms with certain characteristics, “or a bond”, the configuration is referred to when the substituent is such a “bond” that groups that are directly adjacent to the specified substituent are directly linked to each other through a chemically possible bond configuration .

The term “cycloalkyl” refers to cyclic alkyl groups having from 3 to 20 carbon atoms, having one cyclic ring or several fused rings. Such cycloalkyl groups include, by way of example, single ring structures such as cyclopropyl, cyclobutyl, cyclopentyl, cyclooctyl and the like, or a multi ring system such as adamantanil and the like.

Cycloalkyl may optionally be substituted with one or more alkyl, alkenyl, alkoxy, halo, haloalkyl, hydroxy, hydroxyalkyl, aryl, heteroaryl, heterocycle, cycloalkyl, alkanoyl, alkoxycarbonyl, amino, imino, alkylamino, acylamino, nitro, trifluoromethyl carboxyalkyl, keto, thioxo, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, acetamido, acetoxy, acetyl, benzamido, benzenesulfinyl, benzenesulfonamido, benzenesulfonyl, benzenesulfonylamino, benzoyl, benzoyloamino, si, benzyl, benzyloxy, benzyloxycarbonyl, benzylthio, carbamoyl, carbamate, isocyanato, sulfamoyl, sulfinamoyl, sulfino, sulfo, sulfoamino, thiosulfo, NR ^x R ^y and / or COOR ^x , each of R ^x and R ^y independently represent H alkyl, alkenyl, aryl, heteroaryl, heterocycle, cycloalkyl or hydroxy. Cycloalkyl may optionally be at least partially unsaturated, thereby forming cycloalkenyl. In addition, cycloalkyl may optionally be a divalent radical, thereby forming cycloalkylene.

The term "effective amount" refers to an amount sufficient to achieve favorable or necessary results. An effective amount for a given administration is readily determined by a person skilled in the pharmaceutical art.

The term “halo” refers to fluoro, chloro, bromo and iodo. Similarly, the term “halogen” refers to fluoro, chloro, bromo and iodo.

The term "haloalkyl" refers to alkyl substituted by 1-4 halo groups, which may be the same or different. Typical haloalkyl groups include trifluoromethyl, 3-fluorododecyl, 12,12,12-trifluorododecyl, 2-bromoctyl, 3-bromo-6-chlorheptyl and the like.

The term “heteroaryl” is a monocyclic, bicyclic or tricyclic ring system containing one, two or three aromatic rings and containing at least one nitrogen, oxygen or sulfur atom in the aromatic ring and which may be unsubstituted or substituted. Heteroaryl may optionally be a divalent radical, thereby forming heteroarylene. Examples of heteroaryl groups include, but are not limited to, 2H-pyrrolyl, 3H-indolyl, 4H-quinolisinyl, 4H-carbazolyl, acridinyl, benzo [6] thienyl, benzothiazolyl, β-carbolinyl, carbazolyl, chromenyl, cinnolinyl, dibenzo [b, d] furanyl, furazanyl, furyl, imidazolyl, imidizolil, indazolyl, indolizinyl, indolyl, isobenzofuranyl, isoindolyl, isoquinolyl, isothiazolyl, isoxazolyl, naphthyridinyl, naphtho [2,3-b], oxazolyl, pyrimidinyl, phenanthridinyl, phenanthrolinyl, fenarsazinil, phenazinyl phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolyl, quinoxalinyl, thiadiazolyl, thianthrenyl, thiazolyl, thienyl, thiazolyl and xanthenyl. In one embodiment, the term “heteroaryl” means a monocyclic aromatic ring containing five or six atoms in a ring containing carbon and 1, 2, 3 or 4 heteroatoms independently selected from the group consisting of non-peroxidic oxygen, sulfur and N (Z), wherein Z is absent or represents H, O, alkyl, phenyl or benzyl. In another embodiment, heteroaryl means an ortho-fused bicyclic heterocycle containing from about eight to ten atoms in the ring, obtained from, in particular,

a benz derivative or heterocycle obtained by condensation of propylene or a tetramethylene diradical for this purpose.

Heteroaryl may optionally be substituted with one or more alkyl, alkenyl, alkoxy, halo, haloalkyl, hydroxy, hydroxyalkyl, aryl, heteroaryl, heterocycle, cycloalkyl, alkanoyl, alkoxycarbonyl, amino, imino, alkylamino, acylamino, nitro, trifluoromethyl carboxyalkyl, keto, thioxo, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, acetamido, acetoxy, acetyl, benzamido, benzenesulfinyl, benzenesulfonamido, benzenesulfonyl, benzenesulfonylamino, benzoyl, benzoyloamino, si, benzyl, benzyloxy, benzyloxycarbonyl, benzylthio, carbamoyl, carbamate, isocyanato, sulfamoyl, sulfinamoyl, sulfino, sulfo, sulfoamino, thiosulfo, NR ^x R ^y and / or COOR ^x , each of R ^x and R ^y independently represent H alkyl, alkenyl, aryl, heteroaryl, heterocycle, cycloalkyl or hydroxy.

The term “heterocycle” or “heterocyclyl” refers to a saturated or partially unsaturated ring system containing at least one heteroatom selected from the group consisting of oxygen, nitrogen and sulfur, and optionally substituted with alkyl or C (= O) OR ^b , where R ^b represents hydrogen or alkyl. Typically, a heterocycle is a monocyclic, bicyclic or tricyclic group containing one or more heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur. The heterocyclic group may also contain an oxo group (= O) attached to the ring. Non-limiting examples of heterocyclic groups include 1,3-dihydrobenzofuran, 1,3-dioxolane, 1,4-dioxane, 1,4-dithian, 2H-pyran, 2-pyrazoline, 4H-pyran, chranyl, imidazolidinyl, imidazolinyl, indolinyl, isochromanil , isoindolinyl, morpholine, piperazinyl, piperidine, piperidyl, pyrazolidine, pyrazolidinyl, pyrazolinyl, pyrrolidine, pyrroline, quinuclidine and thiomorpholine. The heterocycle may optionally be a divalent radical, thus forming a heterocycle. The heterocycle may optionally be substituted with one or more alkyl, alkenyl, alkoxy, halo, haloalkyl, hydroxy, hydroxyalkyl, aryl, heteroaryl, heterocycle, cycloalkyl, alkanoyl, alkoxycarbonyl, amino, imino, alkylamino, acylamino, nitro, trifluoromethane carboxyalkyl, keto, thioxo, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, acetamido, acetoxy, acetyl, benzamido, benzenesulfinyl, benzenesulfonamido, benzenesulfonyl, benzenesulfonylamino, benzoyl, benzoyloamino, si, benzyl, benzyloxy, benzyloxycarbonyl, benzylthio, carbamoyl, carbamate, isocyanato, sulfamoyl, sulfinamoyl, sulfino, sulfo, sulfoamino, thiosulfo, NR ^x R ^y and / or COOR ^x , each of R ^x and R ^y independently represent H alkyl, alkenyl, aryl, heteroaryl, heterocycle, cycloalkyl or hydroxy.

Examples of nitrogen heterocycles and heteroaryls include, but are not limited to, pyrrole, imidazole, pyrazole, pyridine, pyrazine, pyrimidine, pyridazine, indolizine, isoindole, indole, indazole, purine, quinolizine, isoquinoline, quinazoline, phthalazine, chthalazine, cinnoline, pteridine, carbazole, carboline, phenanthridine, acridine, phenanthroline, isothiazole, phenazine, isoxazole, phenoxazine, phenothiazine, imidazolidine, imidazoline, piperidine, piperazine, indoline, morpholino, piperidoxy azetinyl, tetrahydrin azetethenyl and tetra-azinetethenyl-tetra-azinetetinil motorcycles.

The term "hydrate" refers to a complex in which the solvent molecule is water.

The terms “individual,” “host,” “subject,” and “patient” are used interchangeably and refer to mammals, including, but not limited to, primates, including apes and humans.

The term "metabolite" refers to any compound of formula (I) obtained in vivo or in vitro from a parent drug or prodrug thereof.

Pharmaceutically acceptable salts of the compounds described herein can be synthesized from the parent compound, which contains a basic or acidic moiety, by conventional chemical methods. In general, such salts can be prepared by reacting the free acidic or basic forms of these compounds with a stoichiometric amount of a suitable base or acid in water or in an organic solvent or a mixture of the two; in general, a non-aqueous medium such as ether, ethyl acetate, ethanol, isopropanol and acetonitrile is preferred. Lists of a variety of suitable salts can be found in Remington: The Science and Practice of Pharmacy, 21 ^st edition, Lippincott, Williams & Wilkins, (2005).

Pharmaceutically acceptable prodrugs refer to a compound that is metabolized, for example hydrolyzed or oxidized, in the host to form a compound of formula (I). Typical examples of prodrugs include compounds that have biologically labile protective groups on a functional fragment of the active compound. Prodrugs include compounds that can be oxidized, reduced, aminated, deaminated, hydroxylated, dehydroxylated, hydrolyzed, dehydrolyzed, alkylated, dealkylated, acylated, deacylated, phosphorylated, dephosphorylated to form the active compound.

A prodrug can easily be obtained from compounds of formula (I) using methods known in the art. See, for example, Notan, R.Ε., "Theory and Practice of Prodrug Kinetics," Methods in Enzymology, 112: 309 323 (1985); Bodor, N., "Novel Approaches in Prodrug Design," Drugs of the Future, 6 (3): 165 182 (1981); and Bundgaard, H., "Design of Prodrugs: Bioreversible-Derivatives for Various Functional Groups and Chemical Entities," in Design of Prodrugs (H. Bundgaard, ed.), Elsevier, N.Y. (1985); Burger's Medicinal Chemistry and Drug Chemistry, Fifth Ed., Vol.1, pp. 1772, 949 982 (1995).

The term “solvate” refers to a complex with variable stoichiometry formed by a solute (in the present invention, a compound of formula I or a salt thereof or a physiologically functional derivative) and a solvent. Such solvents for the purposes of the present invention should not interfere with the biological activity of the solute. Non-limiting examples of suitable solvents include, but are not limited to, water, methanol, ethanol, and acetic acid. Preferably, the solvent used is a pharmaceutically acceptable solvent. Non-limiting examples of suitable pharmaceutically acceptable solvents include water, ethanol, and acetic acid.

The phrase "room temperature" refers to a temperature in the range from about 20 ° C to about 30 ° C.

The term "substituted" is intended to mean that one or more hydrogens at the specified atom is replaced by selected from these groups, provided that the normal valency of the specified atom is not exceeded, and that the substitution leads to a stable compound. Suitable indicated groups include, for example, alkyl, alkenyl, alkylidene, alkoxy, halo, haloalkyl, hydroxy, hydroxyalkyl, aryl, heteroaryl, heterocycle, cycloalkyl, alkanoyl, acyloxy, alkoxycarbonyl, amino, imino, alkylamino, acylamino, nitro, trifluoromethyl, , trifluoromethoxy, carboxy, carboxyalkyl, keto, thioxo, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, acetamido, acetoxy, acetyl, benzamido, benzenesulfinyl, benzenesulfonamido, benzenesulfonyl, benzenesulfonylamino, benzoyl, benzoyl, benzyloxy, benzyloxycarbonyl, benzylthio, carbamoyl, carbamate, isocyanato, sulfamoyl, sulfinamoyl, sulfino, sulfo, sulfoamino, thiosulfo, NR ^x R ^y and / or COOR ^x , each of R ^x and R ^y independently being H, alkyl, alkenyl , aryl, heteroaryl, heterocycle, cycloalkyl or hydroxy. When the substituent is an oxo (e.g., = O) or thioxo (e.g. = = S) group, then two hydrogens are substituted at the indicated atom.

The terms “treatment” or “treat” or “treatment” refer to the desired pharmacological and / or physiological effect. The effect may be prophylactic provided that the disease or its symptom is completely or partially prevented and / or may be therapeutic if the disease is partially or completely cured and / or the undesired damage associated with the disease.

The present invention relates to multifunctional quinoline derivatives having the following properties: complexation with a metal, excretion of reactive oxygen species, anti-aggregation, axonal proliferation, and neuron proliferation. They are suitable for the treatment of neurodegenerative diseases, including neuronal toxicity or oxidative stress-induced dysfunction, and other disorders associated with aggregation of improperly folded proteins. In animal models, it was found that quinoline derivatives (B3 or C12) at a concentration of from 1 to 100 mg / kg, preferably from 1 to 10 mg / kg, intraperitoneally daily, improve the memory of mice without causing significant toxicity.

In one aspect, the present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt, solvate or hydrate, prodrug or metabolite thereof

where R ¹ represents hydrogen, (C ₁ -C ₈ ) alkyl, (C ₁ -C ₈ ) alkylene (C ₃ -C ₈ ) cycloalkyl, (C ₁ -C ₈ ) haloalkyl or (C ₁ -C ₈ ) alkylene (C ₆ -C ₂₀ ) aryl;

R ² represents hydrogen or halogen;

R ³ represents hydrogen, halogen, (C ₁ -C ₈ ) alkyl or (C ₁ -C ₈ ) alkoxy;

R ⁴ represents hydrogen, halogen, (C ₁ -C ₈ ) alkyl, (C ₁ -C ₈ ) alkoxy or (C ₁ -C ₈ ) haloalkyl;

R ⁵ represents hydrogen or (C ₁ -C ₂₀ ) alkanol;

R ⁶ represents hydrogen; and

R ⁷ represents hydrogen, (C ₁ -C ₂₀ ) alkanol, (C ₁ -C ₈ ) alkylene (C ₃ -C ₈ ) heterocyclyl (C ₁ -C ₂₀ ) alkanol, (C ₁ -C ₈ ) alkylene (C ₃ -C ₈ ) heterocyclyl (C ₁ -C ₂₀ ) alkyl, (C ₁ -C ₈ ) alkylene (C ₁ -C ₆ ) alkylamino (C ₁ -C ₆ ) alkynyl, (C ₁ -C ₈ ) alkyleneamino (C ₁ -C ₂₀ ) alkanol or (C ₁ -C ₈ ) alkyleneamino (C ₁ -C ₂₀ ) alkanol (C ₁ -C ₈ ) alkylene-substituted (C ₃ -C ₂₀ ) heteroaryl.

In one embodiment of the present invention, where

R ¹ represents hydrogen, CH ₃ , CH ₂ CH ₃ , CH (CH ₃ ) ₂ , CH ₂ CH (CH ₃ ) ₂ , CF ₃ or benzyl;

R ² represents hydrogen, F or Cl;

R ³ represents hydrogen, F, Cl, CH ₃ or OCH ₃ ;

R ⁴ represents hydrogen, F, Cl, Br, CH ₃ , OCH ₃ or CF ₃ ;

R ⁵ represents hydrogen, (CH ₂ ) ₁₁ OH or (CH ₂ ) ₁₂ OH;

R ⁶ represents hydrogen; and

R ⁷ represents hydrogen, (CH ₂ ) ₉ OH, (CH ₂ ) ₁₀ OH, (CH ₂ ) ₁₁ OH, (CH ₂ ) ₁₂ OH, (CH ₂ ) ₁₃ OH, (CH ₂ ) ₁₄ OH, (CH ₂ ) ₁₅ OH, CH ₂ (N (CH ₂ CH ₂ ) ₂ N) CH ₂ CH ₂ OH, CH ₂ (N (CH ₂ CH ₂ ) ₂ N) CH ₂ CH ₃ , CH ₂ N (CH ₃ ) CH ₂ C = CH, CH ₂ NH (CH ₂ ) ₈ OH or CH ₂ N ((CH ₂ ) ₆ OH) CH ₂ (8-methoxyquinolin-2-yl).

In another embodiment of the present invention, where

R ¹ represents hydrogen, CH ₃ , CH ₂ CH ₃ , CH (CH ₃ ) ₂ , CH ₂ CH (CH ₃ ) ₂ , CH ₂ CH (CH ₂ ) ₂ , CF ₃ or benzyl;

R ² , R ³ , R ⁴ , R ⁵ and R ⁶ each independently represents hydrogen; and

R ⁷ represents (CH ₂ ) ₉ OH, (CH ₂ ) ₁₀ OH, (CH ₂ ) ₁₁ OH, (CH ₂ ) ₁₂ OH, (CH ₂ ) ₁₃ OH, (CH ₂ ) ₁₄ OH, (CH ₂ ) ₁₅ OH, CH ₂ (N (CH ₂ CH ₂ ) ₂ N) CH ₂ CH ₂ OH or CH ₂ N (CH ₃ ) CH ₂ C = CH. In another embodiment of the present invention, where

R ¹ represents hydrogen, CH ₃ , CH ₂ CH ₃ , CH ₂ CH (CH ₃ ) ₂ , CH ₂ CH (CH ₂ ) ₂ or CH (CH ₃ ) ₂ ;

R ² , R ³ , R ⁵ and R ⁶ each independently represents hydrogen;

R ⁴ represents CH ₃ , F, Cl, Br, CF ₃ or OCH ₃ ; and

R ⁷ represents (CH ₂ ) ₉ OH, (CH ₂ ) ₁₀ OH, (CH ₂ ) ₁₁ OH, (CH ₂ ) ₁₂ OH, (CH ₂ ) ₁₃ OH, (CH ₂ ) ₁₅ OH, (CH ₂ ) ₁₀ OCOCH ₃ , (CH ₂ ) ₁₁ OCOCH ₃ , (CH ₂ ) ₁₂ OCOCH ₃ , (CH ₂ ) ₁₃ OCOCH ₃ , CH ₂ NH (CH ₂ ) ₈ OH, CH ₂ (N (CH ₂ CH ₂ ) ₂ N ) CH ₂ CH ₂ OH, CH ₂ (N (CH ₂ CH ₂ ) ₂ N) CH ₂ CH ₃ or CH ₂ N (CH ₃ ) CH ₂ C = CH.

In another embodiment of the present invention, where

R ¹ represents hydrogen, CH ₃ , CH ₂ CH ₃ , CH (CH ₂ ) ₂ or CH ₂ CH (CH ₂ ) ₂ ;

R ² , R ⁴ each independently represents Cl;

R ³ , R ⁵ and R ⁶ each independently represents hydrogen; and

R ⁷ represents (CH ₂ ) ₁₁ OH, CH ₂ NH (CH ₂ ) ₈ OH or CH ₂ N (CH ₃ ) CH ₂ C≡CH. In another embodiment of the present invention, where

R ¹ represents hydrogen, CH ₃ , CH ₂ CH ₃ , CH ₂ CH (CH ₃ ) ₂ , CH ₂ CH (CH ₂ ) ₂ , CH (CH ₃ ) ₂ or benzyl;

R ² , R ³ , R ⁴ , R ⁶ and R ⁷ each independently represents hydrogen; and

R ⁵ represents (CH ₂ ) ₁₁ OH or (CH ₂ ) ₁₂ OH.

In another embodiment of the present invention, where

R ¹ represents CH ₃ ;

R ² , R ⁵ and R ⁶ each independently represents hydrogen;

R ³ and R ⁴ each independently represents OCH ₃ or Cl; and

R ⁷ represents (CH ₂ ) ₁₁ OH.

In another embodiment of the present invention, the compound is selected from the group consisting of 9- (8- (benzyloxy) quinolin-2-yl) nonan-1-ol, 10- (8- (benzyloxy) quinolin-2-yl) decan-1 -ol, 11- (8- (benzyloxy) quinolin-2-yl) undecan-1-ol, 12- (8- (benzyloxy) quinolin-2-yl) dodecan-1-ol, 13- (8- (benzyloxy ) quinolin-2-yl) tridecan-1-ol, 14 - ((8- (benzyloxy) quinolin-2-yl) tetradecan-1-ol, 15 - (8- (benzyloxy) quinolin-2-yl) pentadecane- 1-ol, 11- (8- (benzyloxy) -5-methylquinolin-2-yl) undecan-1-ol, 11- (8- (benzyloxy) -6-methylquinolin-2-yl) undecan-1-ol, 11- (8- (benzyloxy) -5-fluoroquinolin-2-yl) undecan-1-ol, 11- (8- (benzyloxy) - 5-chloroquinolin-2-yl) undecan-1-ol, 2- (9-hydroxynonyl) quinolin-8-ol, 2- (10-hydroxydecyl) quinolin-8-ol, 2- (11-hydroxyundecyl) quinolin-8 -ol, 2- (12-hydroxy-dodecyl) quinolin-8-ol, 2- (13-hydroxytridecyl) quinolin-8-ol, 2- (14 - (- hydroxytetradecyl) quinolin-8-ol, 2- (15-hydroxypentadecyl ) quinolin-8-ol, 2- (11-hydroxyundecyl) -5-methylquinolin-8-ol, 2- (11-hydroxyundecyl) -6-methylquinolin-8-ol, 5-chloro-2- (11-hydroxyundecyl) quinolin-8-ol, 9- (8-methoxyquinolin-2-yl) nonan-1-ol, 10- (8-methoxyquinolin-2-yl) decan-1-ol, 11- (8-methoxyquinolin-2-yl ) undecan-1-ol, 12- (8-methoxyquinolin-2-yl) to decan-1-ol, 13- (8-methox quinolin-2-yl) tridecan-1-ol, 14 - ((8-methoxyquinolin-2-yl) tetradecan-1-ol, 15- (8-methoxyquinolin-2-yl) pentadecan-1-ol, 11- ( 8-methoxy-5-methylquinolin-2-yl) undecan-1-ol, 11- (5-fluoro-8-methoxyquinolin-2-yl) undecan-1-ol, 12- (5-fluoro-8-methoxyquinolin- 2-yl) dodecan-1-ol, 9- (5-chloro-8-methoxyquinolin-2-yl) nonan-1-ol, 11- (5-chloro-8-methoxyquinolin-2-yl) undecan-1- ol, 15- (5-chloro-8-methoxyquinolin-2-yl) pentadecan-1-ol, 11- (5-bromo-8-methoxyquinolin-2-yl) undecan-1-ol, 11- (8-methoxy -5- (trifluoromethyl) quinolin-2-yl) undecan-1-ol, 11- (5,8-dimethoxyquinolin-2-yl) undecan-1-ol, 11- (8-methoxy-6-methylquinolin-2- il) undecan-1-ol, 11- (6 -fluoro-8-methoxyquinolin-2-yl) undecan-1-ol, 11- (6-chloro-8-methoxyquinolin-2-yl) undecan-1-ol, 11- (7-fluoro-8-methoxyquinolin-2 -yl) undecan-1-ol, 11- (7-chloro-8-methoxyquinolin-2-yl) undecan-1-ol, 11- (5-chloro-6,8-dimethoxyquinolin-2-yl) undecan-1 -ol, 11- (6-chloro-5,8-dimethoxyquinolin-2-yl) undecan-1-ol, 11- (5,7-dichloro-8-methoxyquinolin-2-yl) undecan-1-ol, 9 - (8-ethoxyquinolin-2-yl) nonan-1-ol, 10- (8-ethoxyquinolin-2-yl) decan-1-ol, 11- (8-ethoxyquinolin-2-yl) undecan-1-ol, 12- (8-ethoxyquinolin-2-yl) dodecan-1-ol, 13- (8-ethoxyquinolin-2-yl) tridecan-1-ol, 14 - ((8-ethoxyquinolin-2-yl) tetradecan-1- ol, 15- (8-ethoxyquinolin-2-yl) penta Ekan-1-ol, 11- (8-ethoxy-5-methylquinolin-2-yl) undecan-1-ol, 11- (8-ethoxy-5-fluoroquinolin-2-yl) undecan-1-ol, 9- (5-chloro-8-ethoxyquinolin-2-yl) nonan-1-ol, 11- (5-chloro-8-ethoxyquinolin-2-yl) undecan-1-ol, 15- (5-chloro-8-ethoxyquinoline -2-yl) pentadecan-1-ol, 11- (5-bromo-8-ethoxyquinolin-2-yl) undecan-1-ol, 11- (5,7-dichloro-8-ethoxyquinolin-2-yl) undecane -1-ol, 9- (8-isopropoxyquinolin-2-yl) nonan-1-ol, 10- (8-isopropoxyquinolin-2-yl) decan-1-ol, 11- (8-isopropoxyquinolin-2-yl) undecan-1-ol, 12- (8-isopropoxyquinolin-2-yl) dodecan-1-ol, 13- (8-isopropoxyquinolin-2-yl) tridecan-1-ol, 14 - ((8-isopropoxyquinolin-2- sludge) tetradecane -1-ol, 15- (8-isopropoxyquinolin-2-yl) pentadecan-1-ol, 11- (8-isopropoxy-5-methylquinolin-2-yl) undecan-1-ol, 11- (5-fluoro- 8-isopropoxyquinolin-2-yl) undecan-1-ol, 9- (5-chloro-8-isopropoxyquinolin-2-yl) nonan-1-ol, 11- (5-chloro-8-isopropoxyquinolin-2-yl) undecan-1-ol, 15- (5-chloro-8-isopropoxyquinolin-2-yl) pentadecan-1-ol, 11- (5-bromo-8-isopropoxyquinolin-2-yl) undecan-1-ol, 15- (5-chloro-8-isopropoxyquinolin-2-yl) pentadecan-1-ol, 11- (5-bromo-8-isopropoxyquinolin-2-yl) undecan-1-ol, 11- (5,7-dichloro-8 -isopropoxyquinolin-2-yl) undecan-1-ol, 9- (8- (cyclopropylmethoxy) quinolin-2-yl) nonan-1-ol, 10- (8- (cyclopropylme toxins) quinolin-2-yl) decan-1-ol, 11- (8- (cyclopropylmethoxy) quinolin-2-yl) undecan-1-ol, 12- (8- (cyclopropylmethoxy) quinolin-2-yl) dodecan- 1-ol, 13- (8- (cyclopropylmethoxy) quinolin-2-yl) tridecan-1-ol, 14 - ((8- (cyclopropylmethoxy) quinolin-2-yl) tetradecan-1-ol, 15- (8- (cyclopropylmethoxy) quinolin-2-yl) pentadecan-1-ol, 11- (8- (cyclopropylmethoxy) -5-methylquinolin-2-yl) undecan-1-ol, 11- (8- (cyclopropylmethoxy) -5-fluoroquinoline -2-yl) undecan-1-ol, 9- (5-chloro-8- (cyclopropylmethoxy) quinolin-2-yl) nonan-1-ol, 11- (5-chloro-8- (cyclopropylmethoxy) quinolin-2 -yl) undecan-1-ol, 15- (5-chloro-8- (cyclopropylmethoxy) quinolin-2 -yl) pentadecan-1-ol, 11- (5-bromo-8- (cyclopropylmethoxy) quinolin-2-yl) undecan-1-ol, 11- (5,7-dichloro-8- (cyclopropylmethoxy) quinolin-2 -yl) undecan-1-ol, 5,7-dichloro-2- (11-hydroxyundecyl) quinolin-8-ol, 10- (5-chloro-8-methoxyquinolin-2-yl) decan-1-ol, 10 - (5-chloro-8-methoxyquinolin-2-yl) decyl ester of acetic acid, 11- (5-chloro-8-methoxyquinolin-2-yl) undecan-1-ol, 11- (5-chloro-8-methoxyquinoline -2-yl) undecyl ester of acetic acid, 12- (5-chloro-8-methoxyquinolin-2-yl) dodecan-1-ol, 12- (5-chloro-8-methoxyquinolin-2-yl) dodecyl ester of acetic acid 13- (5-chloro-8-methoxyquinolin-2-yl) tridecan-1-ol, 13 - (5-chloro-8-methoxyquinolin-2-yl) tridecyl ester of acetic acid, 11- (8-methoxyquinolin-4 - (- yl) undecan-1-ol, 11- (8-ethoxyquinolin-4 - (- yl ) undecan-1-ol, 11- (8-isopropoxyquinolin-4 - (- yl) undecan-1-ol, 11- (8- (cyclopropylmethoxy) quinolin-4 - (- yl) undecan-1-ol, 11- (8- (benzyloxy) quinolin-4 - (- yl) undecan-1-ol, 12- (8- (benzyloxy) quinolin-4 - (- yl) dodecan-1-ol, 4 - ((11-hydroxyundecyl) quinolin-8-ol, 4 - ((12-hydroxydodecyl) quinolin-8-ol, 9- (8- (trifluoromethoxy) quinolin-2-yl) nonan-1-ol, 11- (8- (trifluoromethoxy) quinolin- 2-yl) undecan-1-ol, 14 - ((8- (trifluoromethoxy) quinolin-2-yl) tetradecan-1-ol, 15- (8- (trifluoromethoxy) chi olin-2-yl) pentadecan-1-ol, 2 - ((4 - ((2-hydroxyethyl) piperazin-1-yl) methyl) quinolin-8-ol, 2- (4 - (((5-chloro 8-methoxyquinolin-2-yl) methyl) piperazin-1-yl) ethanol, 2- (4 - (((5-chloro-8-ethoxyquinolin-2-yl) methyl) piperazin-1-yl) ethanol, 2- (4 - (((5-chloro-8-isopropoxyquinolin-2-yl) methyl) piperazin-1-yl) ethanol, 2- (4 - (((5-chloro-8- (cyclopropylmethoxy) quinolin-2-yl ) methyl) piperazin-1-yl) ethane, 2- (4 - (((5,7-dichloro-8-methoxyquinolin-2-yl) methyl) piperazin-1-yl) ethanol, 2- (4 - (( (5,7-dichloro-8- (cyclopropylmethoxy) quinolin-2-yl) methyl) piperazin-1-yl) ethanol, 2 - ((methyl (prop-2-ynyl) amino) methyl) quinolin-8-ol, 5-chloro-2 - ((methyl (prop-2-ynyl) am but) methyl) quinolin-8-ol, N ((5-chloro-8-methoxyquinolin-2-yl) methyl) -N-methylprop-2-in-1-amine, N [((5-chloro-8- ethoxyquinolin-2-yl) methyl) -N-methylprop-2-yn-1-amine, N ((5-chloro-8-isopropoxyquinolin-2-yl) methyl) -N-methylprop-2-yn-1-amine N ((5-chloro-8- (cyclopropylmethoxy) quinolin-2-yl) methyl) -N-methylprop-2-yn-1-amine, N ((5,7-dichloro-8-methoxyquinolin-2-yl ) methyl) -N-methylprop-2-yn-1-amine, N ((5,7-dichloro-8- (cyclopropylmethoxy) quinolin-2-yl) methyl) -N-methylprop-2-yn-1-amine , 8 - ((5-chloro-8-methoxyquinolin-2-yl) methylamino) octan-1-ol, 8 - ((5-chloro-8-methoxyquinolin-2-yl) methylamino) octan-1-ol, 8 - ((5-chloro-8-isopropoxyquinolin-2-yl) meth amylamino) octan-1-ol, 8 - ((5-chloro-8- (cyclopropylmethoxy) quinolin-2-yl) methylamino) octan-1-ol, 8 - ((5,7-dichloro-8-methoxyquinolin-2 -yl) methylamino) octan-1-ol, 8 - ((5,7-dichloro-8- (cyclopropylmethoxy) quinolin-2-yl) methylamino) octan-1-ol and 6- (bis ((8-methoxyquinoline- 2-yl) methyl) amino) hexan-1-ol.

In another aspect, the present invention relates to a composition comprising the aforementioned compound or a pharmaceutically acceptable salt, solvate or hydrate thereof, prodrug or metabolite and a pharmaceutically acceptable diluent or carrier for use in the treatment of a neurodegenerative disease.

In one embodiment of the present invention, the neurodegenerative disease is selected from the group consisting of Alzheimer's disease, amyotrophic lateral sclerosis (ALS), cataracts, cognitive impairment, ischemic cerebral stroke, cerebral palsy, stroke, hemorrhagic stroke, Creutzfelcephalopathy, Yakutia rabies, dementia, depression, Down syndrome, epilepsy, post-traumatic epilepsy, frontotemporal dementia, Gille de la Tourette syndrome, Halle disease Boden-Spatz, Huntington’s disease, Levy’s disease, Parkinson’s disease, cognitive impairment, learning deficiency, macular degeneration, memory deficiency, multiple sclerosis, multiple systemic atrophy, motor neuron disease, Peak disease, progressive supranuclear palsy, pseudodementia, retinopathy, senile , schizophrenic transient anoxic induced neurodegeneration, pain, traumatic brain damage and spinal cord injury.

CHEMISTRY

Example 1 - Preparation of (8-benzyloxyquinolin-2-yl) - and (8-hydroxyquinolin-2-yl) alkyl alcohol

Reagents and conditions: (a) BnBr, KOH, EtOH, reflux, 15 hours; (b) 1) LHMDS (lithium hexamethyldisilazane), THF, 0 ° C, 1 h; 2) Br (CH ₂ ) _n-1 OH, room temperature 16-36 h; (c) H ₂ , Pd / C, MeOH, room temperature from 6 to 10 hours; (d) BCl ₃ , CH ₂ Cl ₂ , 0 ° C. to room temperature for 3 hours.

Method: Benzylation was performed as described in G. Serratrice et al. [Tetrahedron, 1996, 52, 4659-4672]. Benzyl bromide (6.45 g, 37.7 mmol) was added to a mixed solution of 2-methylquinaldine (5.0 g, 31.4 mmol) and KOH (1.95 g, 34.8 mmol) in 60 ml EtOH under heating with reflux condenser. After 15 hours, the reaction mixture was filtered, and the filtrate was removed in vacuo. The residue was purified by flash column chromatography with Hex / EA (6: 1) and recrystallized with hexane to give an intermediate. LHMDS (2.2 to 2.5 equiv.) Was treated with a mixed solution (1 equiv.) In 20 ml of THF at 0 ° C. for 1 h.

Br (CH ₂ ) _n-1 OH (1.0 to 1.2 equiv.) Was added to the reaction mixture and the temperature was restored to room temperature (RT) for an additional 15 to 36 hours. The solvent was removed under reduced pressure. The brown oily residue was purified by flash column chromatography with Hex / EA (3: 1 to 2: 1) or DCM / EA (15: 1 to 9: 1) and recrystallized with hexane / EA to give a number of compounds A. Removal of the benzyl group in a number of compounds A was carried out in the presence of 10% Pd / C in a hydrogen atmosphere at room temperature for 6-10 hours. The reaction mixture was filtered and the filtrate was purified by flash column chromatography with Hex / EA (4: 1 to 3: 1) to obtain a number of compounds B. To a mixed solution of All (0.65 g, 1.4 mmol) in 20 ml of CH ₂ Cl _{2 was} added 1M BCl ₃ (2.8 ml, 2.8 mmol) in an ice bath for 3 hours. The reaction mixture was poured into an ice bath and extracted with 50 ml of CH ₂ Cl ₂ . The organic layer was concentrated in vacuo and the residue was purified by flash column chromatography (EA) to give the product (0.31 g, 60%).

9- (8- (benzyloxy) quinolin-2-yl) nonan-1-ol (A1)

Yield (YD): 53%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.15 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 6.8 Hz, 2H), 7.31 ~ 7, 41 (m, 5H), 7.29 (d, J = 2.0 Hz, 1H), 7.15 (dd, J = 7.6, 2.0 Hz, 1H), 5.40 (s, 2H ), 3.52 (t, J = 6.8 Hz, 2H), 3.00 (t, J = 8.0 Hz, 2H), 1.80 (quin, J = 6.8 Hz, 2H), 1.50 (t, J = 7.2 Hz, 2H); 1.28-1.42 (br, 11H); MS. m / z 400.0, [M + Na] ⁺ .

10- (8- (benzyloxy) quinolin-2-yl) decan-1-ol (A2)

YD: 41%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.14 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 7.6 Hz, 2H), 7.32-7, 42 (m, 5H), 7.28 (t, J = 7.2 Hz, 1H), 7.14 (dd, J = 7.6, 1.2 Hz, 1H), 5.38 (s, 2H ), 3.51 (t, J = 6.8 Hz, 2H), 2.98 (t, J = 8.0 Hz, 2H), 1.79 (quin, J = 7.2 Hz, 2H), 1.49 (t, J = 6.8 Hz, 2H); 1.29-1.40 (br, 13H); MS. m / z 414.0, [M + Na] ⁺ .

11- (8- (benzyloxy) quinolin-2-yl) undecan-1-ol (A3)

YD: 42%. ¹ Η NMR (400 MHz, CDCl ₃ ) δ 8.02 (d, J = 8.4 Hz, 1H), 7.53 (d, J = 7.2 Hz, 2H), 7.27-7.39 (m, 6H), 7.02 (d, J = 7.6 Hz, 1H), 5.46 (s, 2H), 3.63 (t, J = 6.8 Hz, 2H), 3.05 (t, J = 8 Hz, 2H), 1.84 (q, J = 7.6 Hz, 3H), 1.56 (t, J = 7.2 Hz, 2H), 1.29-1.46 (m, 12H); MS. m / z 428.3, [M + Na] ⁺ .

12- (8- (benzyloxy) quinolin-2-yl) dodecan-1-ol (A4)

YD: 44%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.13 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 7.6 Hz, 2H), 7.31-7, 40 (m, 5H), 7.26 (d, J = 7.6 Hz, 1H), 7.13 (dd, J = 7.6, 0.8 Hz, 1H), 5.37 (s, 2H ), 3.51 (t, J = 6.8 Hz, 2H), 2.98 (t, J = 7.6 Hz, 2H), 1.78 (quin, J = 7.2 Hz, 2H), 1.49 (quin, J = 7.2 Hz, 2H); 1.25-1.41 (m, 17H); MS. m / z 442.3, [M + Na] ⁺ .

13- (8- (benzyloxy) quinolin-2-yl) tridecan-1-ol (A5)

YD: 40%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.95 (d, J = 8.4 Hz, 1H), 7.45 (d, J = 7.6 Hz, 2H), 7.19-7.30 (m, 5H), 6.93 (d, J = 7.6 Hz, 1H), 5.40 (s, 2H), 3.55 (t, J = 6.8 Hz, 2H), 2.99 (t, J = 7.6 Hz, 2H), 1.77 (quin, J = 7.6 Hz, 2H), 1.46 (t, J = 6.8 Hz, 2H), 1.19-1 38 (br, 19H); MS. m / z 456.3, [M + Na] ⁺ .

14- (8- (benzyloxy) quinolin-2-yl) tetradecan-1-ol (A6)

YD: 51%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.14 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 7.2 Hz, 2H), 7.33-7, 42 (m, 5H), 7.28 (t, J = 7.2 Hz, 1H), 7.14 (d, J = 6.8 Hz, 1H), 5.38 (s, 2H), 3, 52 (t, J = 6.4 Hz, 2H), 2.98 (t, J = 8.0 Hz, 2H), 1.50 (quin, J = 6.8 Hz, 2H), 1.47 ( t, J = 6.8 Hz, 2H); 1.22-1.41 (br, 21H); MS. m / z 447.3, [M + H] ⁺ .

15- (8- (benzyloxy) quinolin-2-yl) pentadecan-1-ol (A7)

YD: 42%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.15 (d, J = 8.4 Hz, 1H), 7.53 (d, J = 7.2 Hz, 2H), 7.35-7, 43 (m, 5H), 7.28-7.33 (m, 1H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 5.39 (s, 2H), 3 , 52 (t, J = 6.8 Hz, 2H), 2.99 (t, J = 8.0 Hz, 2H), 1.79 (quin, J = 6.8 Hz, 2H), 1.51 (quin, J = 6.8 Hz, 2H); 1.22-1.41 (br, 23H); MS. m / z 462.3, [M + H] ⁺ .

11- (8- (benzyloxy) -5-methylquinolin-2-yl) undecan-1-ol (A8)

YD: 47%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.30 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 7.2 Hz, 2H), 7.44 (d, J = 8.8 Hz, 1H), 7.26-7.36 (m, 3H), 7.17 (d, J = 8.0 Hz, 2H), 7.02 (d, J = 8.0 Hz, 2H), 5.36 (s, 2H), 3.52 (t, J = 6.4 Hz, 2H), 3.00 (t, J = 7.6 Hz, 2H), 2.55 ( s, 3H), 1.80 (quin, J = 7.2 Hz, 2H), 1.50 (quin, J = 6.8 Hz, 2H), 1.28-1.41 (m, 15H); MS. m / z 420.3, [M + H] ⁺ .

11- (8- (benzyloxy) -6-methylquinolin-2-yl) undecan-1-ol (A9)

YD: 40%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.03 (d, J = 8.4 Hz, 1H), 7.53 (d, J = 7.2 Hz, 2H), 7.33-7, 37 (m, 3H), 7.26-7.30 (m, 1H), 7.16 (s, 1H), 7.00 (d, J = 1.2 Hz, 2H), 5.36 (s , 2H), 3.51 (t, J = 6.8 Hz, 2H), 2.95 (t, J = 7.6 Hz, 2H), 2.40 (s, 3H), 1.76 (q , J = 7.6 Hz, 2H), 1.56 (t, J = 7.2 Hz, 2H), 1.29-1.46 (m, 15H); MS. m / z 442.3, [M + Na] ⁺ .

11- (8- (benzyloxy) -5-fluoroquinolin-2-yl) undecan-1-ol (A10)

YD: 43%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.28 (d, J = 8.8 Hz, 1H), 7.51 (d, J = 7.2 Hz, 2H), 7.33-7.40 (m, 3H), 7.28 (t, J = 8.0 Hz, 1H), 6.89-6.98 (m, 2H), 5.42 (s, 2H), 3.61 (t, J = 6.4 Hz, 2H), 3.07 (t, J = 8 Hz, 2H), 1.83 (q, J = 7.6 Hz, 2H), 1.51-1.54 (m, 2H), 1.21-1.45 (m, 15H); MS. m / z 446.2, [M + Na] ⁺ .

11- (8- (benzyloxy) -5-chloroquinolin-2-yl) undecan-1-ol (A11)

YD: 43%. H NMR (400 MHz, d4-MeOD) δ 8.48 (d, J = 8.8 Hz, 1H), 7.52-7.57 (m, 3H), 7.46 (d, J = 8, 4 Hz, 1H), 7.35 ~ 7.39 (m, 2H), 7.31 (d, J = 7.2 Hz, 1H), 7.14 (d, J = 8.4 Hz, 1H) , 5.40 (s, 2H), 3.52 (t, J = 6.8 Hz, 2H), 3.03 (t, J = 7.6 Hz, 2H), 1.81 (quin, J = 7.2 Hz, 2H), 1.49 (t, J = 6.8 Hz, 2H), 1.28-1.41 (m, 15H); MS. m / z 462.2, [M + Na] ⁺ .

2- (9-hydroxynonyl) quinolin-8-ol (B1)

YD: 85%. ¹ H NMR (400 MHz, d4-MeOD) δ 7.86 (d, J = 8.4 Hz, 1H), 7.22 (t, J = 7.6 Hz, 1H), 7.03-7, 13 (m, 3H), 3.50 (t, J = 6.8 Hz, 2H), 2.75 (t, J = 8.0 Hz, 2H), 1.58 (quin, J = 6.8 Hz, 2H), 1.44 (quin, J = 6.8 Hz, 2H), 1.10-1.20 (m, 11H); High Resolution Mass Spectrometry (ESI): Calculated for [C ₁₈ H ₂₅ NO ₂ -Na] ⁺ : 310.1778, Found: 310.1779.

2- (10-hydroxydecyl) quinolin-8-ol (B2)

YD: 85%. ¹ Η NMR (400 MHz, CDCl ₃ ) δ 8.01 (d, J = 8.4 Hz, 1H), 7.35 (t, J = 6.8 Hz, 1H), 7.26-7.28 (m , 2H), 7.11 (d, J = 7.2 Hz, 1H), 3.60 (t, J = 6.4 Hz, 2H), 2.92 (t, J = 7.6 Hz, 2H ), 1.79 (quin, J = 6.8 Hz, 2H), 1.53 (quin, J = 6.8 Hz, 2H), 1.27-1.33 (br, 14H); MS. m / z 302.2, [M + H] ⁺ .

2- (11-hydroxyundecyl) quinolin-8-ol (B3)

YD: 77%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.04 (d, J = 8.4 Hz, 1H), 7.38 (t, J = 7.8 Hz, 1H), 7.27-7.31 (m, 2H), 7.14 (dd, J = 1.2, 7.6 Hz, 1H), 3.64 (t, J = 6.8 Hz, 2H), 2.95 (t, J = 7.8 Hz, 2H), 1.83 (quin, J = 7.8 Hz, 2H), 1.55 (m, 2H), 1.28-1.36 (br, 17H); ¹ ms. m / z 316.2, [M + H] ⁺ .

2- (12-hydroxydodecyl) quinolin-8-ol (B4)

YD: 76%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.03 (d, J = 8.4 Hz, 1H), 7.36 (t, J = 8 Hz, 1H), 7.25-7.30 (m , 2H), 7.13 (d, J = 7.6 Hz, 1H), 3.62 (t, J = 6.4 Hz, 2H), 2.94 (t, J = 7.6 Hz, 2H ), 1.81 (quin, J = 7.6 Hz, 2H), 1.54 (quin, J = 6.8 Hz, 2H), 1.29-1.38 (br, 18H); MS. m / z 330.3, [M + H] ⁺ .

2- (13-hydroxytridecyl) quinolin-8-ol (B5)

YD: 84%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.03 (d, J = 8.4 Hz, 1H), 7.36 (t, J = 7.6 Hz, 1H), 7.26-7.30 (m, 2H), 7.13 (d, J = 7.6 Hz, 1H), 3.62 (t, J = 6.8 Hz, 2H), 2.95 (t, J = 7.6 Hz , 2H), 1.81 (quin, J = 7.2 Hz, 2H), 1.54 (quin, J = 6.8 Hz, 2H), 1.25-1.34 (br, 20H); MS. m / z 344.3, [M + H] ⁺ .

2- (14-hydroxytetradecyl) quinolin-8-ol (B6)

YD: 87%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.02 (d, J = 8.8 Hz, 1H), 7.36 (t, J = 7.6 Hz, 1H), 7.25-7.29 (m , 2H), 7.12 (d, J = 7.2 Hz, 1H), 3.61 (t, J = 6.4 Hz, 2H), 2.94 (t, J = 7.6 Hz, 2H ), 1.80 (quin, J = 7.2 Hz, 2H), 1.54 (quin, J = 6.8 Hz, 2H), 1.24-1.34 (br, 24H); MS. m / z 358.3, [M + H] ⁺ .

2- (15-hydroxypentadecyl) quinolin-8-ol (B7)

YD: 83%. ¹ Η NMR (400 MHz, CDCl ₃ ) δ 8.04 (d, J = 8.4 Hz, 1H), 7.35 (t, J = 7.6 Hz, 1H), 7.26-7.29 (m, 2H), 7.13 (d, J = 7.2 Hz, 1H), 3.62 (t, J = 6.8 Hz, 2H), 2.95 (t, J = 7.6 Hz , 2H), 1.80 (quin, J = 7.2 Hz, 2H), 1.54 (quin, J = 7.2 Hz, 2H), 1.24-1.37 (br, 24H); MS. m / z 372.3, [M + H] ⁺ .

2- (11-hydroxyundecyl) -5-methylquinolin-8-ol (B8)

YD: 83%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.26 (d, J = 8.4 Hz, 1H), 7.39 (d, J = 8.8 Hz, 1H), 7.15 (d, J = 7.2 Hz, 1H), 6.93 (d, J = 3.2 Hz, 1H), 3.52 (t, J = 6.4 Hz, 2H), 2.95 (t, J = 8.0 Hz, 2H), 2.53 (s, 3H), 1.81 (quin, J = 7.2 Hz, 2H), 1.48 (quin, J = 6.8 Hz, 2H), 1 13-1.37 (m, 15H); MS. m / z 330.3, [M + H] ⁺ .

2- (11-hydroxyundecyl) -6-methylquinolin-8-ol (B9)

YD: 83%. ¹ H NMR (400 MHz, d4-MeOD) δ 7.99 (d, J = 8.4 Hz, 1H), 7.29 (d, J = 8.8 Hz, 1H), 7.06 (s, 1H), 6.91 (s, 1H), 3.51 (t, J = 6.4 Hz, 2H), 2.90 (t, J = 8.0 Hz, 2H), 2.41 (s, 3H), 1.77 (quin, J = 6.4 Hz, 2H), 1.49 (quin, J = 6.8 Hz, 2H), 1.25-1.37 (m, 19H); MS. m / z 352.2, [M + Na] ⁺ .

5-chloro-2- (11-hydroxyundecyl) quinolin-8-ol (B10)

¹ H NMR (400 MHz, d4-MeOD) δ 8.39 (d, J = 8.8 Hz, 1H), 7.49 (d, J = 8.8 Hz, 1H), 7.41 (d, J = 8.4 Hz, 1H), 7.01 (d, J = 8.0 Hz, 1H), 3.51 (t, J = 6.4 Hz, 2H), 2.98 (t, J = 8.0 Hz, 2H), 1.81 (quin, J = 7.2 Hz, 2H), 1.50 (quin, J = 6.8 Hz, 2H), 1.27-1.35 (m, 15H); MS. m / z 350.2, [M + H] ⁺ .

Example 2 - Preparation of (8-methoxyquinol-2-yl) alkyl alcohol

Reagents and conditions: (a) MeI, K ₂ CO ₃ , acetone, room temperature, 10 hours; (b) 1) LHMDS, THF, 0 ° C, 1 h; 2) Br (CH ₂ ) _n-1 OH, room temperature, 12-30 h.

Method: Methyl iodide (10.8 g, 76.3 mmol) was added to a mixed solution of 2-methylquinaldine (1.0 g, 6.3 mmol) and K ₂ CO ₃ (5.0 g, 36.2 mmol) in 30 ml of acetone at room temperature for 10 hours. The reaction mixture was filtered and the filtrate was removed under reduced pressure. The residue was purified by flash column chromatography with Hex / EA (3: 1) and recrystallized with hexane / EA to give 8-methoxy-2-methylquinoline as an intermediate. LHMDS (2.2 to 2.5 equiv.) Was treated with a mixed solution of the intermediate compound (1 equiv.) In THF at 0 ° C. for 1 h. Corresponding Br (CH ₂ ) _n-1 OH (1.0 to 1.2 equiv.) Was added to the reaction mixture and the temperature was restored to room temperature for an additional 12 to 30 hours. The solvent was removed under reduced pressure. The brown oily residue was purified by flash column chromatography with Hex / EA or DCM / EA and recrystallized using Hex / EA to give a number of compounds C.

9- (8-methoxyquinolin-2-yl) nonan-1-ol (C1)

YD: 50%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.05 (d, J = 8.4 Hz, 1H), 7.33-7.42 (m, 3H), 7.04 (d, J = 6, 8 Hz, 1H), 4.08 (s, 3H), 3.62 (t, J = 6.4 Hz, 2H), 3.07 (t, J = 7.6 Hz, 2H), 1.79 (br, 2H); 1.53 (br, 2H); 1.30-1.42 (br, 11H); MS. m / z 324.0, [M + Na] ⁺ .

10- (8-methoxyquinolin-2-yl) decan-1-ol (C2)

YD: 38%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.01 (d, J = 8.4 Hz, 1H), 7.36 (t, J = 7.6 Hz, 1H), 7.30-7.33 (m, 2H), 7.00 (d, J = 7.6 Hz, 1H), 4.05 (s, 3H), 3.60 (t, J = 6.8 Hz, 2H), 3.01 (t, J = 7.6 Hz, 2H), 1.79 (quin, J = 8 Hz, 2H), 1.52 (quin, J = 6.8 Hz, 2H), 1.30-1.43 (br, 12H); MS. m / z 316.2, [M + H] ⁺ .

11- (8-methoxyquinolin-2-yl) undecan-1-ol (C3)

YD: 42%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.02 (d, J = 8.8 Hz, 1H), 7.38 (t, J = 7.8 Hz, 1H), 7.31-7.34 (m, 2H), 7.15 (d, J = 7.2 Hz, 1H), 4.06 (s, 3H), 3.61 (t, J = 6.8 Hz, 2H), 3.02 (t, J = 7.8 Hz, 2H), 1.79 (quin, J = 7.6 Hz, 2H), 1.54 (quin, J = 6.8 Hz, 2H), 1.31-1 42 (br, 15H); MS. m / z 352.2, [M + Na] ⁺ .

12- (8-methoxyquinolin-2-yl) dodecan-1-ol (C4)

YD: 38%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.01 (d, J = 8.8 Hz, 1H), 7.35 (t, J = 7.6 Hz, 1H), 7.30-7.32 (m , 2H), 7.01 (d, J = 7.2 Hz, 1H), 4.05 (s, 3H), 3.61 (t, J = 6.4 Hz, 2H), 3.01 (t , J = 8 Hz, 2H), 1.78 (quin, J = 7.6 Hz, 2H), 1.36-1.41 (m, 2H), 1.24-1.33 (br, 16H) ; MS. m / z 344.3, [M + H] ⁺ .

13- (8-methoxyquinolin-2-yl) tridecan-1-ol (C5)

YD: 38%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.01 (d, J = 8.4 Hz, 1H), 7.37 (t, J = 7.6 Hz, 1H), 7.30-7.33 (m , 2H), 7.01 (d, J = 7.6 Hz, 1H), 4.05 (s, 3H), 3.61 (t, J = 7.2 Hz, 2H), 3.01 (t , J = 8 Hz, 2H), 1.80 (quin, J = 7.6 Hz, 2H), 1.54 (quin, J = 6.8 Hz, 2H), 1.36-1.43 (br , 19H); MS. m / z 358.3, [M + H] ⁺ .

14- (8-methoxyquinolin-2-yl) tetradecan-1-ol (C6)

YD: 38%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.02 (d, J = 8.4 Hz, 1H), 7.31-7.38 (m, 3H), 7.01 (d, J = 7, 2 Hz, 1H), 4.06 (s, 3H), 3.61 (t, J = 6.8 Hz, 2H), 3.02 (t, J = 8 Hz, 2H), 1.79 (quin , J = 7.6 Hz, 2H), 1.54 (quin, J = 6.8 Hz, 2H), 1.23-1.40 (br, 21H); MS. m / z 394.3, [M + Na] ⁺ .

15- (8-methoxyquinolin-2-yl) pentadecan-1-ol (C7)

YD: 31%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.01 (d, J = 8.4 Hz, 1H), 7.31-7.39 (m, 3H), 7.01 (d, J = 7, 2 Hz, 1H), 4.06 (s, 3H), 3.63 (t, J = 6.8 Hz, 2H), 3.02 (t, J = 8 Hz, 2H), 1.79 (quin , J = 7.6 Hz, 2H), 1.54 (quin, J = 6.8 Hz, 2H), 1.32-1.43 (br, 23H); MS. m / z 408.3, [M + H] ⁺ .

11- (8-methoxy-5-methylquinolin-2-yl) undecan-1-ol (C8)

YD: 30%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.29 (d, J = 8.4 Hz, 1H), 7.43 (d, J = 8.8 Hz, 1H), 7.24 (dd, J = 8.0, 0.8 Hz, 1H), 7.01 (d, J = 8.0 Hz, 1H), 4.00 (s, 3H), 3.51 (t, J = 6.8 Hz, 2H), 2.97 (t, J = 8.0 Hz, 2H), 2.56 (s, 3H), 1.76 (quin, J = 7.6 Hz, 2H), 1.50 ( quin, J = 7.2 Hz, 2H); 1.27-1.40 (br, 15H); MS. m / z 366.2, [M + Na] ⁺ .

11- (5-fluoro-8-methoxyquinolin-2-yl) undecan-1-ol (C9)

¹ H NMR (400 MHz, d4-MeOD) δ 8.34 (d, J = 8.8 Hz, 1H), 7.51 (d, J = 8.8 Hz, 1H), 7.15 (d, J = 7.2 Hz, 1H), 6.93 (d, J = 3.2 Hz, 1H), 4.02 (s, 3H), 3.52 (t, J = 6.8 Hz, 2H) 2.95 (t, J = 8.0 Hz, 2H), 1.81 (quin, J = 7.2 Hz, 2H), 1.48 (quin, J = 6.8 Hz, 2H), 1 13-1.37 (m, 15H); MS. m / z 370.2, [M + Na] ⁺ .

12- (5-fluoro-8-methoxyquinolin-2-yl) dodecan-1-ol (C10)

YD: 38%. 1 H NMR (400 MHz, d4-MeOD) δ 8.36 (d, J = 8.8 Hz, 1H), 7.52 (d, J = 8.8 Hz, 1H), 7.17 (d, J = 8.8 Hz, 1H), 7.08 (dd, J = 8.4, 4.8 Hz, 1H), 4.04 (s, 3H), 3.53 (t, J = 6.8 Hz , 2H), 3.00 (t, J = 8.0 Hz, 2H), 1.78 (quin, J = 7.2 Hz, 2H), 1.51 (quin, J = 7.2 Hz, 2H ), 1.28-1.42 (m, 17H); MS. m / z 384.2, [M + Na] ⁺ .

9- (5-chloro-8-methoxyquinolin-2-yl) nonan-1-ol (C11)

YD: 38%. ¹ Η NMR (400 MHz, d4-MeOD) δ 8.47 (d, J = 8.8 Hz, 1H), 7.55 (d, J = 8.8 Hz, 1H), 7.52 (d, J = 8.4 Hz, 1H), 7.11 (d, J = 8.8 Hz, 1H), 4.04 (s, 3H), 3.51 (t, J = 6.8 Hz, 2H) 3.00 (t, J = 8.0 Hz, 2H), 1.77 (quin, J = 7.6 Hz, 2H), 1.50 (quin, J = 6.8 Hz, 2H), 1 30-1.37 (m, 11H); MS. m / z 336.2, [M + H] ⁺ .

11- (5-chloro-8-methoxyquinolin-2-yl) undecan-1-ol (C12)

YD: 35%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.46 (d, J = 8.4 Hz, 1H), 7.54 (d, J = 8.8 Hz, 1H), 7.51 (d, J = 8.4 Hz, 1H), 7.10 (d, J = 8.4 Hz, 1H), 4.04 (s, 3H), 3.51 (t, J = 6.8 Hz, 2H) , 2.99 (t, J = 8.0 Hz, 2H), 1.76 (quin, J = 7.6 Hz, 2H), 1.49 (quin, J = 6.8 Hz, 2H), 1 27-1.38 (br, 15H); MS. m / z 386.2, [M + Na] ⁺ .

15- (5-chloro-8-methoxyquinolin-2-yl) pentadecan-1-ol (C13)

YD: 39%. ¹ H NMR (400 MHz, d4-MeOD + CDCl ₃ ) δ 8.44 (d, J = 8.4 Hz, 1H), 7.47 (d, J = 8.4 Hz, 1H), 7.46 (d, J = 8.4 Hz, 1H), 7.01 (dd, J = 8.4, 4.0 Hz, 1H), 4.03 (s, 3H), 3.52 (t, J = 6.8 Hz, 2H), 2.99 (t, J = 8.0 Hz, 2H), 1.76 (quin, J = 7.6 Hz, 2H), 1.50 (quin, J = 6, 8 Hz, 2H); 1.22-1.38 (m, 23H); MS. m / z 442.3, [M + Na] ⁺ .

11- (5-bromo-8-methoxyquinolin-2-yl) undecan-1-ol (C14)

YD: 46%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.40 (d, J = 8.4 Hz, 1H), 7.65 (d, J = 8.4 Hz, 1H), 7.44 (d, J = 8.8 Hz, 1H), 6.91 (d, J = 8.4 Hz, 1H), 4.06 (s, 3H), 3.63 (t, J = 6.8 Hz, 2H), 3.07 (t, J = 8.0 Hz, 2H), 1.79 (quin, J = 7.6 Hz, 2H), 1.55 (quin, J = 6.8 Hz, 2H), 1, 30-1.45 (br, 15H); MS. m / z 430.2, [M + Na] ⁺ .

11- (8-methoxy-5- (trifluoromethyl) quinolin-2-yl) undecan-1-ol (C15)

YD: 36%. ¹ Η NMR (400 MHz, d4-MeOD + CDCl ₃ ) δ 8.40 (dq, J = 10.4, 1.6 Hz, 1H), 7.86 (d, J = 8.4 Hz, 1H) , 7.58 (d, J = 8.8 Hz, 1H), 7.20 (d, J = 8.0 Hz, 1H), 4.11 (s, 3H), 3.51 (t, J = 6.8 Hz, 2H), 3.00 (t, J = 8.0 Hz, 2H), 1.78 (quin, J = 7.6 Hz, 2H), 1.50 (quin, J = 6, 8 Hz, 2H), 1.27-1.43 (m, 15H); MS. m / z 420.2, [M + Na] ⁺ .

11- (5,8-dimethoxyquinolin-2-yl) undecan-1-ol (C16)

YD: 31%; ¹ H NMR (400 MHz, d4-MeOD) δ 8.46 (d, J = 8.4 Hz, 1H), 7.38 (d, J = 8.4 Hz, 1H), 7.03 (d, J = 8.4 Hz, 1H), 6.82 (d, J = 8.4 Hz, 1H), 3.98 (s, 3H), 3.94 (s, 3H), 3.51 (t, J = 6.8 Hz, 2H), 2.95 (t, J = 8.0 Hz, 2H), 1.73 (quin, J = 7.6 Hz, 2H), 1.50 (quin, J = 6.8 Hz, 2H); 1.27-1.35 (br, 15H); MS. m / z 360.2, [M + H] ⁺ .

11- (8-methoxy-6-methylquinolin-2-yl) undecan-1-ol (C17)

YD: 41%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.96 (d, J = 8.4 Hz, 1H), 7.30 (t, J = 8.4 Hz, 1H), 7.12 (s, 1H ), 6.87 (s, 1H), 4.06 (s, 3H), 3.63 (t, J = 6.8 Hz, 2H), 3.05 (t, J = 7.6 Hz, 2H ), 2.50 (s, 3H), 1.79 (quin, J = 8.0 Hz, 2H), 1.55 (quin, J = 6.8 Hz, 2H), 1.27-1.41 (br, 15H); MS. m / z 366.2, [M + Na] ⁺ .

11- (6-fluoro-8-methoxychino lin-2-yl) und Ekan-1-ol (C18)

YD: 41%; ¹ H NMR (400 MHz, d4-MeOD) δ 8.12 (d, J = 8.4 Hz, 1H), 7.44 (d, J = 8.8 Hz, 1H), 7.07 (dd, J = 9.2, 2.4 Hz, 1H), 7.01 (dd, J = 10.8, 2.8 Hz, 1H), 4.06 (s, 3H), 3.52 (t, J = 6.8 Hz, 2H), 2.95 (t, J = 8.0 Hz, 2H), 1.75 (quin, J = 7.6 Hz, 2H), 1.48 (quin, J = 7 , 2 Hz, 2H); 1.19-1.35 (m, 15H); MS. m / z 348.2, [M + H] ⁺ .

11- (6-chloro-8-methoxyquinolin-2-yl) undecan-1-ol (C19)

YD: 39%; ¹ H NMR (400 MHz, d4-MeOD) δ 8.11 (d, J = 8.4 Hz, 1H), 7.44-7.47 (m, 2H), 7.13 (d, J = 2 , 0 Hz, 1H), 4.05 (s, 3H), 3.52 (t, J = 6.8 Hz, 2H), 2.96 (t, J = 8.0 Hz, 2H), 1, 76 (quin, J = 7.2 Hz, 2H), 1.50 (quin, J = 6.8 Hz, 2H), 1.28-1.36 (br, 15H); MS. m / z 360.2, [M + H] ⁺ .

11- (7-fluoro-8-methoxyquinolin-2-yl) undecan-1-ol (C20)

YD: 32%; ¹ H NMR (400 MHz, d4-MeOD) δ 8.20 (d, J = 8.8 Hz, 1H), 7.60 (dd, J = 8.8, 5.6 Hz, 1H), 7, 39 (dd, J = 8.8, 1.6 Hz, 1H), 7.01 (d, J = 8.8 Hz, 1H), 4.13 (d, J = 1.2 Hz, 3H), 3.52 (t, J = 6.8 Hz, 2H), 2.99 (t, J = 7.6 Hz, 2H), 1.80 (quin, J = 7.6 Hz, 2H), 1, 48 (quin, J = 6.8 Hz, 2H), 1.29-1.42 (m, 15H); MS. m / z 348.2, [M + H] ⁺ .

11- (7-chloro-8-methoxyquinolin-2-yl) undecan-1-ol (C21)

YD: 17%; ¹ H NMR (400 MHz, d4-MeOD) δ 8.20 (d, J = 8.4 Hz, 1H), 7.60 (d, J = 8.8 Hz, 1H), 7.50 (d, J = 8.8 Hz, 1H), 7.42 (d, J = 8.4 Hz, 1H), 4.08 (s, 3H), 3.52 (t, J = 6.8 Hz, 2H) , 2.99 (t, J = 7.6 Hz, 2H), 1.82 (quin, J = 7.2 Hz, 2H), 1.50 (quin, J = 6.8 Hz, 2H), 1 28-1.42 (br, 15H); MS. m / z 360.2, [M + H] ⁺ .

11- (5-chloro-6,8-dimethoxyquinolin-2-yl) undecan-1-ol (C22)

YD: 32%; ¹ H NMR (400 MHz, d4-MeOD) δ 8.40 (d, J = 8.8 Hz, 1H), 7.46 (d, J = 8.8 Hz, 1H), 7.07 (s, 1H), 4.08 (s, 3H), 4.02 (s, 3H), 3.51 (t, J = 6.8 Hz, 2H), 2.94 (t, J = 7.6 Hz, 2H), 1.74 (quin, J = 7.6 Hz, 2H), 1.50 (quin, J = 6.8 Hz, 2H), 1.27-1.34 (br, 15H); MS. m / z 394.2, [M + H] ⁺ .

11- (6-chloro-5,8-dimethoxyquinolin-2-yl) undecan-1-ol (C23)

YD: 35%; ¹ H NMR (400 MHz, d4-MeOD) δ 8.38 (d, J = 8.8 Hz, 1H), 7.51 (d, J = 8.4 Hz, 1H), 7.12 (s, 1H), 4.02 (s, 3H), 3.94 (s, 3H), 3.52 (t, J = 6.4 Hz, 2H), 2.97 (t, J = 7.6 Hz, 2H), 1.74 (quin, J = 7.6 Hz, 2H), 1.50 (quin, J = 6.8 Hz, 2H), 1.34-1.41 (br, 15H); MS. m / z 394.2, [M + H] ⁺ .

11- (5,7-dichloro-8-methoxyquinolin-2-yl) undecan-1-ol (C24)

YD: 40%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.40 (d, J = 8.4 Hz, 1H), 7.59 (d, J = 8.0 Hz, 1H), 7.56 (s, 1H ), 7.39 (d, J = 8.8 Hz, 1H), 4.19 (s, 3H), 3.63 (t, J = 6.8 Hz, 2H), 3.04 (t, J = 7.6 Hz, 2H), 1.84 (quin, J = 7.2 Hz, 2H), 1.55 (quin, J = 6.8 Hz, 2H), 1.27-1.40 (br , 15H); MS. m / z 420.2, [M + Na] ⁺ .

Example 3 - Preparation of (8-ethoxyquinol-2-yl) - and (8-isopropoxyquinol-2-yl) alkyl alcohols

Reagents and conditions: (a) Ethyl iodide or 2-bromopropane, K ₂ CO ₃ , DMF, 60 ° C, 14 hours; (b) 1) LHMDS, THF, 0 ° C, 1 h; 2) Br (CH ₂ ) _n-1 OH, room temperature, 12-30 h.

Method: Ethyl iodide (3.9 g, 25.0 mmol) or 2-bromopropane (2.4 g, 19.2 mmol) was added to a mixed solution of 2-methylquinaldine (3.0 g, 18.8 mmol) and K ₂ CO ₃ (6.5 g, 47 mmol; 5.2 g, 37.6 mmol) in 30 ml of DMF at 60 ° C for 14 hours. The reaction was quenched with H ₂ O (200 ml) and extracted with EtOAc (50 ml X 2). The organic layer was concentrated by evaporation in vacuo. The residue was purified by flash column chromatography with Hex / EA (6: 1) and recrystallized with hexane / EA to give 8-ethoxy-2-methylquinoline as an intermediate (2.75 g, 78%) as a solid, but liquid for 8-isopropoxy-2-methylquinoline (2.92 g, 77%). LHMDS (2.2 equiv.) Was treated with a mixed solution of various intermediates in a THF solution at 0 ° C. for 1 h. The corresponding Br (CH ₂ ) _n-1 OH (1.1-1.2 equiv.) Was added to the reaction mixtures, and the temperature was restored to room temperature for an additional 12 to 30 hours. The solvent was removed under reduced pressure. The brown oily residue was purified by Hex / EA or DCM / EA flash column chromatography and recrystallized by hexane / EA to give compound D and E.

9- (8-ethoxyquinolin-2-yl) nonan-1-ol (D1)

YD: 45%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.07 (d, J = 8.0 Hz, 1H), 7.34-7.42 (m, 3H), 7.06 (d, J = 8, 4 Hz, 1H), 4.35 (q, J = 6.8 Hz, 2H), 3.63 (t, J = 6.8 Hz, 2H), 3.11 (br, 2H), 1.83 (quin, J = 7.6 Hz, 2H), 1.52-1.64 (m, 5H), 1.26-1.46 (br, 11H); MS. m / z 338.0, [M + Na] ⁺ .

10- (8-ethoxyquinolin-2-yl) decan-1-ol (D2)

YD: 36%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.16 (d, J = 8.4 Hz, 1H), 7.38-7.44 (m, 3H), 7.14 (dd, J = 7 , 2, 1.6 Hz, 1H), 4.29 (q, J = 6.8 Hz, 2H), 3.52 (t, J = 6.8 Hz, 2H), 2.99 (t, J = 7.6 Hz, 2H), 1.78 (quin, J = 7.6 Hz, 2H), 1.57 (t, J = 7.6 Hz, 3H), 1.50 (t, J = 7 6 Hz, 2H); 1.30-1.43 (br, 13H); MS. m / z 352.0, [M + Na] ⁺ .

11- (8-ethoxyquinolin-2-yl) undecan-1-ol (D3)

YD: 43%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.03 (d, J = 7.6 Hz, 1H), 7.31-7.41 (m, 3H), 7.04 (d, J = 7, 2 Hz, 1H), 4.33 (q, J = 7.2 Hz, 2H), 3.62 (t, J = 6.4 Hz, 2H), 3.06 (br, 2H), 1.81 (quin, J = 8.0 Hz, 2H), 1.51-1.61 (m, 6H), 1.38-1.51 (br, 14H); MS. m / z 344.3, [M + H] ⁺ .

12- (8-ethoxyquinolin-2-yl) dodecan-1-ol (D4)

YD: 33%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.03 (d, J = 8.4 Hz, 1H), 7.31-7.39 (m, 3H), 7.04 (d, J = 7, 6 Hz, 1H), 4.33 (q, J = 6.8 Hz, 2H), 3.62 (t, J = 6.4 Hz, 2H), 3.05 (t, J = 8.0 Hz , 2H), 1.82 (quin, J = 7.2 Hz, 2H), 1.53-1.62 (m, 5H), 1.27-1.42 (br, 17H); MS. m / z 380.3, [M + Na] ⁺ .

13- (8-ethoxyquinolin-2-yl) tridecan-1-ol (D5)

YD: 43%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.04 (d, J = 8.4 Hz, 1H), 7.32-7.40 (m, 3H), 7.04 (d, J = 7, 6 Hz, 1H), 4.34 (q, J = 6.8 Hz, 2H), 3.62 (t, J = 6.4 Hz, 2H), 3.07 (t, J = 8.0 Hz , 2H), 1.82 (quin, J = 7.6 Hz, 2H), 1.52-1.62 (m, 5H), 1.19-1.46 (br, 19H); MS. m / z 394.0, [M + Na] ⁺ .

14- (8-ethoxyquinolin-2-yl) tetradecan-1-ol (D6)

YD: 35%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.00 (d, J = 8.4 Hz, 1H), 7.28-7.35 (m, 3H), 7.02 (d, J = 7, 2 Hz, 1H), 4.32 (q, J = 6.8 Hz, 2H), 3.61 (t, J = 6.4 Hz, 2H), 3.01 (t, J = 8.0 Hz , 2H), 1.80 (quin, J = 7.6 Hz, 2H), 1.52-1.60 (m, 5H), 1.24-1.41 (br, 21H); MS. m / z 408.3, [M + Na] ⁺ .

15- (8-ethoxyquinolin-2-yl) pentadecan-1-ol (D7)

YD: 33%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.21 (d, J = 8.4 Hz, 1H), 7.40-7.47 (m, 3H), 7.17 (dd, J = 7 , 2, 1.6 Hz, 1H), 4.30 (q, J = 7.2 Hz, 2H), 3.52 (t, J = 6.8 Hz, 2H), 3.01 (t, J = 7.6 Hz, 2H), 1.78 (quin, J = 7.6 Hz, 2H), 1.57 (t, J = 6.8 Hz, 3H), 1.51 (quin, J = 6 8 Hz, 2H); 1.26-1.43 (br, 23H); MS. m / z 400.4, [M + Na] ⁺ .

11- (8-ethoxy-5-methylquinolin-2-yl) undecan-1-ol (D8)

YD: 34%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.20 (d, J = 8.8 Hz, 1H), 7.36 (d, J = 8.4 Hz, 1H), 7.19 (d, J = 7.6 Hz, 1H), 6.94 (d, J = 8.0 Hz, 1H), 4.31 (q, J = 6.8 Hz, 2H), 3.63 (t, J = 6 , 4 Hz, 2H), 3.08 (t, J = 8.0 Hz, 2H), 2.57 (s, 3H), 1.83 (quin, J = 7.6 Hz, 2H), 1, 83 (t, J = 7.6 Hz, 3H), 1.57 (quin, J = 7.2 Hz, 2H), 1.41-1.45 (m, 2H), 1.28-1.33 (br, 13H); MS. m / z 380.2, [M + Na] ⁺ .

11- (8-ethoxy-5-fluoroquinolin-2-yl) undecan-1-ol (D9)

YD: 49%. ¹ Η NMR (400 MHz, d4-MeOD) δ 8.33 (d, J = 8.4 Hz, 1H), 7.49 (d, J = 8.8 Hz, 1H), 7.12 (t, J = 9.2 Hz, 1H), 7.05 (dd, J = 8.4, 4.8 Hz, 1H), 4.25 (q, J = 7.2 Hz, 2H), 3.51 ( t, J = 6.8 Hz, 2H), 2.99 (t, J = 8.0 Hz, 2H), 1.77 (quin, J = 7.2 Hz, 2H), 1.55 (t, J = 7.2 Hz, 3H), 1.48-1.52 (m, 2H), 1.28-1.46 (br, 15H); MS. m / z 384.2, [M + Na] ⁺ .

9- (5-chloro-8-ethoxyquinolin-2-yl) nonan-1-ol (D10)

YD: 34%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.47 (d, J = 8.8 Hz, 1H), 7.55 (d, J = 8.8 Hz, 1H), 7.50 (d, J = 8.4 Hz, 1H), 7.10 (d, J = 8.8 Hz, 1H), 4.28 (q, J = 6.8 Hz, 2H), 3.51 (t, J = 6.4 Hz, 2H), 3.01 (t, J = 8.0 Hz, 2H), 1.76 (quin, J = 7.6 Hz, 2H), 1.56 (t, J = 6, 8 Hz, 3H), 1.48-1.51 (m, 2H), 1.31-1.46 (br, PN); MS. m / z 350.2, [M + H] ⁺ .

11- (5-chloro-8-ethoxyquinolin-2-yl) undecan-1-ol (D11)

YD: 38%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.35 (d, J = 8.8 Hz, 1H), 7.36 (dd, J = 8.4, 3.6 Hz, 1H), 7.19 (d, J = 2.4 Hz, 1H), 6.88 (d, J = 8.4 Hz, 1H), 4.25 (q, J = 7.2 Hz, 2H), 3.56 (t , J = 6.4 Hz, 2H), 2.98 (t, J = 8.0 Hz, 2H), 1.76 (quin, J = 8.0 Hz, 2H), 1.45-l, 54 (m, 5H); 1.19-1.39 (br, 15H); MS. m / z 400.2, [M + Na] ⁺ .

15- (5-chloro-8-ethoxyquinolin-2-yl) pentadecan-1-ol (D12)

YD: 38%. ¹ H NMR (400 MHz, d4-MeOD + CDCl ₃ ) δ 8.47 (d, J = 8.8 Hz, 1H), 7.53 (d, J = 8.8 Hz, 1H), 7.49 (d, J = 8.4 Hz, 1H), 7.08 (d, J = 8.4 Hz, 1H), 4.28 (q, J = 6.8 Hz, 2H), 3.52 (t , J = 6.8 Hz, 2H), 3.01 (t, J = 8.0 Hz, 2H), 1.79 (quin, J = 7.6 Hz, 2H), 1.57 (t, J = 6.8 Hz, 3H), 1.49 (quin, J = 6.8 Hz, 2H), 1.25-1.41 (br, 23H); MS. m / z 434.3, [M + H] ⁺ .

11- (5-bromo-8-ethoxyquinolin-2-yl) undecan-1-ol (D13)

YD: 33%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.41 (d, J = 8.8 Hz, 1H), 7.67 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 8.8 Hz, 1H), 7.04 (d, J = 8.4 Hz, 1H), 4.27 (q, J = 7.2 Hz, 2H), 3.52 (t, J = 6.8 Hz, 2H), 3.00 (t, J = 8.0 Hz, 2H), 1.77 (quin, J = 7.6 Hz, 2H), 1.56 (t, J = 7, 2 Hz, 3H), 1.47-1.57 (m, 2H), 1.27-1.39 (br, 15H); MS. m / z 444.2, [M + Na] ⁺ .

11- (5,7-dichloro-8-ethoxyquinolin-2-yl) undecan-1-ol (D14)

YD: 34%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.43 (d, J = 8.8 Hz, 1H), 7.64 (s, 1H), 7.51 (d, J = 8.4 Hz, 1H), 4.39 (q, J = 6.8 Hz, 2H), 3.52 (t, J = 6.8 Hz, 2H), 3.00 (t, J = 7.2 Hz, 2H) 1.84 (quin, J = 7.2 Hz, 2H); 1.45-1.49 (m, 5H); 1.27-1.36 (br, 15H); MS. m / z 434.2, [M + Na] ⁺ .

9- (8-isopropoxyquinolin-2-yl) nonan-1-ol (E1)

YD: 28%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.07 (d, J = 8.8 Hz, 1H), 7.33-7.36 (m, 1H), 7.31-7.33 (m , 2H), 7.09 (d, J = 7.2 Hz, 1H), 4.79 (m, 1H), 3.49 (t, J = 6.8 Hz, 2H), 2.93 (t , J = 7.6 Hz, 2H), 1.71 (quin, J = 7.6 Hz, 2H), 1.45-1.49 (m, 2H), 1.41 (d, J = 6 Hz 6H); 1.20-1.35 (br, 11H); MS. m / z 330.2, [M + H] ⁺ .

10- (8-isopropoxyquinolin-2-yl) decan-1-ol (E2)

YD: 36%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.14 (d, J = 8.8 Hz, 1H), 7.40-7.43 (m, 1H), 7.37-7.39 (m , 2H), 7.16 (dd, J = 6.8, 2.0 Hz, 1H), 4.83 (m, 1H), 3.51 (t, J = 6.8 Hz, 2H), 2 98 (t, J = 7.6 Hz, 2H), 1.77 (quin, J = 7.2 Hz, 2H), 1.45-1.49 (m, 2H), 1.41 (d, J = 6 Hz, 6H), 1.20-1.35 (br, 11H); MS. m / z 366.0, [M + Na] ⁺ .

11- (8-isopropoxyquinolin-2-yl) undecan-1-ol (E3)

YD: 45%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.99 (d, J = 8.4 Hz, 1H), 7.34 (d, J = 4.4 Hz, 2H), 7.24-7.27 (m, 1H), 7.09 (t, J = 4.4 Hz, 1H), 4.82 (sept, J = 6 Hz, 1H), 3.60 (t, J = 6.8 Hz, 2H ), 3.00 (t, J = 7.6 Hz, 2H), 1.81 (quin, J = 7.6 Hz, 2H), 1.51-1.56 (m, 2H), 1.47 (d, J = 6 Hz, 6H), 1.33-1.43 (br, 15H); MS. m / z 380.3, [M + Na] ⁺ .

12- (8-isopropoxyquinolin-2-yl) dodecan-1-ol (E4)

YD: 34%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.05 (d, J = 7.6 Hz, 1H), 7.30-7.39 (m, 3H), 7.13 (dd, J = 6, 4, 2.4 Hz, 1H), 4.85 (sept, J = 6 Hz, 1H), 3.63 (t, J = 6.8 Hz, 2H), 3.09 (br, 2H), 1 84 (quin, J = 7.6 Hz, 2H), 1.56 (quin, J = 7.2 Hz, 2H), 1.48 (d, J = 6 Hz, 6H), 1.27-1 47 (br, 17H); MS. m / z 394.3, [M + Na] ⁺ .

13- (8-isopropoxyquinolin-2-yl) tridecan-1-ol (E5)

YD: 34%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.11 (d, J = 8.4 Hz, 1H), 7.35-7.41 (m, 3H), 7.14 (d, J = 7 , 2 Hz, 1H), 4.81 (br, 1H), 3.52 (t, J = 6.8 Hz, 2H), 2.96 (t, J = 8.0 Hz, 2H), 1, 75 (quin, J = 7.2 Hz, 2H), 1.45-1.52 (m, 2H), 1.43 (d, J = 6.0 Hz, 6H), 1.25-1.42 (br, 19H); MS. m / z 408.0, [M + Na] ⁺ .

14- (8-isopropoxyquinolin-2-yl) tetradecan-1-ol (E6)

YD: 36%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.13 (d, J = 8.8 Hz, 1H), 7.37-7.43 (m, 3H), 7.16 (dd, J = 7 , 2, 1.6 Hz, 1H), 4.86 (br, 1H), 3.52 (t, J = 6.8 Hz, 2H), 2.98 (t, J = 7.6 Hz, 2H ), 1.78 (quin, J = 7.6 Hz, 2H), 1.49-1.52 (m, 2H), 1.46 (d, J = 6.4 Hz, 6H), 1.26 -1.41 (br, 21H); MS. m / z 422.3, [M + Na] ⁺ .

15- (8-isopropoxyquinolin-2-yl) pentadecan-1-ol (E7)

YD: 36%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.01 (d, J = 8.4 Hz, 1H), 7.27-7.36 (m, 3H), 7.10-7.13 (m, 1H), 4.82 (sept, J = 4.1 Hz, 1H), 3.61 (t, J = 6.8 Hz, 2H), 3.00 (t, J = 6.4 Hz, 2H) 1.81 (quin, J = 7.6 Hz, 2H), 1.52-1.55 (m, 2H), 1.48 (d, J = 2 Hz, 6H), 1.31-1, 47 (br, 21H); MS. m / z 436.3, [M + Na] ⁺ .

11- (8-isopropoxy-5-methylquinolin-2-yl) undecan-1-ol (E8)

YD: 48%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.09 (d, J = 8.4 Hz, 1H), 7.26 (d, J = 8.8 Hz, 1H), 7.12 (d, J = 8.0 Hz, 1H), 6.97 (t, J = 7.6 Hz, 1H), 4.75 (sept, J = 6 Hz, 1H), 3.55 (t, J = 6.8 Hz, 2H), 3.00 (t, J = 7.6 Hz, 2H), 2.51 (s, 3H), 1.81 (t, J = 7.2 Hz, 2H), 1.23- 1.49 (br, 23H); MS. m / z 394.3, [M + Na] ⁺ .

11- (5-fluoro-8-isopropoxyquinolin-2-yl) undecan-1-ol (E9)

YD: 46%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.30 (d, J = 8.8 Hz, 1H), 7.44 (d, J = 8.4 Hz, 1H), 7.09 (d, J = 4.8 Hz, 1H), 4.79 (m, 1H), 3.51 (t, J = 6.8 Hz, 2H), 2.97 (t, J = 8.0 Hz, 2H) 1.74 (quin, J = 7.6 Hz, 2H), 1.45-1.51 (m, 2H), 1.42 (d, J = 6.4 Hz, 6H), 1.12- 1.39 (br, 15H); MS. m / z 398.2, [M + Na] ⁺ .

9- (5-chloro-8-isopropoxyquinolin-2-yl) nonan-1-ol (E10)

YD: 46%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.45 (d, J = 8.8 Hz, 1H), 7.52 (d, J = 8.4 Hz, 1H), 7.49 (d, J = 8.4 Hz, 1H), 7.12 (d, J = 8.4 Hz, 1H), 4.85 (m, 1H), 3.51 (t, J = 6.4 Hz, 2H), 3.01 (t, J = 8.0 Hz, 2H), 1.78 (quin, J = 7.6 Hz, 2H), 1.49 (quin, J = 6.4 Hz, 2H), 1, 45 (d, J = 6.0 Hz, 6H), 1.30-1.42 (br, 11H); MS. m / z 364.2, [M + H] ⁺ .

11- (5-chloro-8-isopropoxyquinolin-2-yl) undecan-1-ol (E11)

YD: 46%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.47 (d, J = 8.4 Hz, 1H), 7.53 (d, J = 8.4 Hz, 1H), 7.50 (d, J = 8.4 Hz, 1H), 7.13 (d, J = 8.4 Hz, 1H), 4.89 (m, 1H), 3.52 (t, J = 6.4 Hz, 2H), 3.01 (t, J = 7.2 Hz, 2H), 1.79 (quin, J = 7.6 Hz, 2H), 1.48 (quin, J = 6.8 Hz, 2H), 1, 41 (d, J = 5.6 Hz, 6H), 1.21 ~ 1.39 (br, 15H); MS. m / z 414.2, [M + Na] ⁺ .

15- (5-chloro-8-isopropoxyquinolin-2-yl) pentadecan-1-ol (E12)

YD: 46%. ¹ H NMR (400 MHz, d4-MeOD + CDCl ₃ ) δ8.46 (d, J = 8.8 Hz, 1H), 7.51 (d, J = 8.8 Hz, 1H), 7.48 ( d, J = 8.8 Hz, 1H), 7.11 (d, J = 8.4 Hz, 1H), 4.85 (m, 1H), 3.52 (t, J = 6.8 Hz, 2H), 3.01 (t, J = 8.0 Hz, 2H), 1.79 (quin, J = 7.2 Hz, 2H), 1.51 (quin, J = 6.8 Hz, 2H) 1.46 (d, J = 6.0 Hz, 6H); 1.25-1.39 (m, 23H); MS. m / z 448.3, [M + H] ⁺ .

11- (5-bromo-8-isopropoxyquinolin-2-yl) undecan-1-ol (E13)

YD: 40%. ¹ H NMR (400 MHz, d4-MeOD) δ8.43 (d, J = 8.8 Hz, 1H), 7.69 (d, J = 8.8 Hz, 1H), 7.52 (d, J = 8.4 Hz, 1H), 7.10 (d, J = 7.6 Hz, 1H), 4.86 (br, 1H), 3.52 (t, J = 6.8 Hz, 2H), 3.02 (t, J = 7.6 Hz, 2H), 1.79 (quin, J = 7.2 Hz, 2H), 1.50-1.52 (m, 2H), 1.46 (d , J = 6.0 Hz, 6H); 1.28-1.41 (br, 15H); MS. m / z 458.2, [M + Na] ⁺ .

11- (5,7-dichloro-8-isopropoxyquinolin-2-yl) undecan-1-ol (E14)

YD: 37%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.36 (d, J = 8.4 Hz, 1H), 7.56 (d, J = 3.2 Hz, 1H), 7.35 (d, J = 8.4 Hz, 1H), 5.13 (m, 1H), 3.63 (t, J = 6.8 Hz, 2H), 3.00 (t, J = 7.6 Hz, 2H), 1 86 (quin, J = 6.8 Hz, 2H); 1.52-1.59 (m, 4H); 1.27-1.44 (br, 20H); MS. m / z 448.4, [M + Na] ⁺ .

Example 4 - Preparation of Derivatives of (8-cyclopropylmethoxyquinol-2-yl) alkyl alcohols

Reagents and conditions: (a) methylenecyclopropyl bromide, K ₂ CO _3, DMF, 60 ° C, 13 h; (b) 1) LHMDS, THF, 0 ° C, 1 h; 2) Br (CH ₂ ) _n-1 OH, room temperature, 12-20 h.

Method: Methylene cyclopropyl bromide (1.0 g, 6.3 mmol) was added to a mixed solution of 2-methylquinaldine (1.0 g, 6.3 mmol) and K ₂ CO ₃ (2.5 g, 18.1 mmol) in 25 ml of DMF at 60 ° C. for 13 hours. The reaction was quenched with H ₂ O (200 ml) and extracted with EtOAc (30 ml X 3). The organic layer was concentrated by evaporation in vacuo, and the residue was purified by flash column chromatography with Hex / EA (8: 1 to 6: 1) to give 5-chloro-8- (cyclopropylmethoxy) -2-methylquinoline as an intermediate. LHMDS (2.2 equiv.) Was treated with a mixed solution of the intermediate compound (0.5 g, 2.3 mmol) in a THF solution at 0 ° C. for 1 h. Corresponding Br (CH ₂ ) _n-1 OH (1.1 -1.2 equiv.) Was added to the reaction mixture, and the temperature was restored to room temperature for an additional 12 to 20 hours. The solvent was removed under reduced pressure. The brown oily residue was purified by Hex / EA or DCM / EA flash column chromatography and recrystallized by Hex / EA to give compound F.

9- (8- (cyclopropylmethoxy) quinolin-2-yl) nonan-1-ol (F1)

YD: 49%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.15 (d, J = 8.4 Hz, 1H), 7.38-7.43 (m, 3H), 7.14 (dd, J = 5 6, 3.2 Hz, 1H), 4.06 (d, J = 7.2 Hz, 2H), 3.51 (t, J = 6.8 Hz, 2H), 3.00 (t, J = 8.0 Hz, 2H), 1.77 (quin, J = 7.6 Hz, 2H), 1.48-1.52 (m, 3H), 1.32-1.47 (m, PN) 0.65-0.70 (m, 2H); 0.34-0.45 (m, 2H); MS. m / z 342.2, [M + H] ⁺ .

10- (8- (cyclopropylmethoxy) quinolin-2-yl) decan-1-ol (F2)

YD: 43%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.16 (d, J = 8.4 Hz, 1H), 7.40 ~ 7.43 (m, 3H), 7.15 (dd, J = 5 , 6, 3.2 Hz, 1H), 4.07 (d, J = 7.2 Hz, 2H), 3.52 (t, J = 6.4 Hz, 2H), 3.01 (t, J = 8.0 Hz, 2H), 1.80 (quin, J = 7.6 Hz, 2H), 1.47-1.53 (m, 3H), 1.31-1.44 (m, 13H) 0.67-0.69 (m, 2H); 0.44-0.46 (m, 2H); MS. m / z 356.2, [M + H] ⁺ .

11- (8- (cyclopropylmethoxy) quinolin-2-yl) undecan-1-ol (F3)

YD: 45%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.02 (d, J = 8.4 Hz, 1H), 7.30 ~ 7.38 (m, 2H), 7.05 (dd, J = 6, 4, 2.4 Hz, 1H), 4.11 (d, J = 6.8 Hz, 1H), 3.63 (t, J = 6.4 Hz, 2H), 3.04 (t, J = 8.0 Hz, 2H), 1.83 (quin, J = 7.6 Hz, 2H), 1.48-1.59 (m, 3H), 1.26-1.46 (br, 15H), 0.67 (dd, J = 13.2, 5.6 Hz, 2H); 0.44 (dd, J = 13.2, 5.6 Hz, 2H); MS. m / z 392.2, [M + Na] ⁺ .

12- (8- (cyclopropylmethoxy) quinolin-2-yl) dodecan-1-ol (F4)

YD: 36%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.01 (d, J = 8.4 Hz, 1H), 7.29-7.38 (m, 3H), 7.06 (dd, J = 6, 0, 2.4 Hz, 1H), 4.11 (d, J = 6.8 Hz, 1H), 3.63 (t, J = 6.4 Hz, 2H), 3.04 (t, J = 7.2 Hz, 2H), 1.83 (quin, J = 7.6 Hz, 2H), 1.48-1.59 (m, 3H), 1.27-1.47 (br, 17H), 0.67 (dd, J = 13.2, 5.6 Hz, 2H); 0.42-0.48 (m, 2H); MS. m / z 384.3, [M + H] ⁺ .

13- (8- (cyclopropylmethoxy) quinolin-2-yl) tridecan-1-ol (F5)

YD: 42%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.14 (d, J = 8.4 Hz, 1H), 7.38 ~ 7.41 (m, 3H), 7.05 (dd, J = 5 , 6, 3.2 Hz, 1H), 4.05 (d, J = 6.8 Hz, 2H), 3.52 (t, J = 6.4 Hz, 2H), 2.99 (t, J = 8.0 Hz, 2H), 1.78 (quin, J = 7.6 Hz, 2H), 1.44-1.52 (m, 3H), 1.26-1.40 (m, 19H) 0.67 (dd, J = 13.2, 5.6 Hz, 2H); 0.40-0.47 (m, 2H); MS. m / z 420.0, [M + Na] ⁺ .

14- (8- (cyclopropylmethoxy) quinolin-2-yl) tetradecan-1-ol (F6)

YD: 37%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.15 (d, J = 8.8 Hz, 1H), 7.39 ~ 7.42 (m, 3H), 7.13 (dd, J = 5 6, 3.2 Hz, 1H), 4.05 (d, J = 6.8 Hz, 2H), 3.52 (t, J = 6.8 Hz, 2H), 2.99 (t, J = 7.6 Hz, 2H), 1.78 (quin, J = 7.6 Hz, 2H), 1.44-1.52 (m, 3H), 1.26-1.43 (m, 21H) 0.65-0.69 (m, 2H); 0.42 (dd, J = 10.0, 4.8 Hz, 2H); MS. m / z 434.3, [M + Na] ⁺ .

15- (8- (cyclopropylmethoxy) quinolin-2-yl) pentadecan-1-ol (F7)

YD: 69%. ¹ H NMR (400 MHz, d4-MeOD + CDCl ₃ ) δ 8.13 (dd, J = 8.4, 2.0 Hz, 1H), 7.38 (br, 3H), 7.11 (d, J = 2.4 Hz, 1H), 4.05 (d, J = 6.8 Hz, 2H), 3.52 (t, J = 6.8 Hz, 2H), 2.99 (t, J = 8.0 Hz, 2H), 1.78 (quin, J = 7.2 Hz, 2H), 1.46-1.52 (m, 3H), 1.25-1.44 (m, 23H), 0.63-0.69 (m, 2H); 0.40-0.46 (m, 2H); MS. m / z 426.4, [M + H] ⁺ .

11- (8- (cyclopropylmethoxy) -5-methylquinolin-2-yl) undecan-1-ol (F8)

YD: 45%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.31 (d, J = 8.8 Hz, 1H), δ 7.44 (d, J = 8.8 Hz, 1H), 7.22 (d , J = 8.0 Hz, 1H), 7.02 (d, J = 8.0 Hz, 1H), 4.02 (d, J = 7.2 Hz, 2H), 3.52 (t, J = 6.4 Hz, 2H), 3.00 (t, J = 8.0 Hz, 2H), 2.57 (s, 3H), 1.79 (quin, J = 7.2 Hz, 2H), 1.29-1.52 (m, 18H), 0.65-0.68 (m, 2H), 0.40-0.43 (m, 2H); MS. m / z 406.3, [M + Na] ⁺ .

11- (8- (cyclopropylmethoxy) -5-fluoroquinolin-2-yl) undecan-1-ol (F9)

YD: 46%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.36 (d, J = 8.8 Hz, 1H), 7.52 (d, J = 8.8 Hz, 1H), 7.07-7, 15 (m, 2H), 4.05 (d, J = 6.8 Hz, 2H), 3.53 (t, J = 6.8 Hz, 2H), 3.02 (t, J = 7.6 Hz, 2H), 1.79 (quin, J = 7.6 Hz, 2H), 1.42-1.49 (m, 3H), 1.22-1.40 (m, 15H), 0.65 -0.69 (m, 2H), 0.42 (dd, J = 10.4, 4.8 Hz, 2H); MS. m / z 410.2, [M + Na] ⁺ .

9- (5-chloro-8- (cyclopropylmethoxy) quinolin-2-yl) nonan-1-ol (F10)

YD: 33%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.48 (d, J = 8.8 Hz, 1H), 7.55 (d, J = 8.8 Hz 1H), 7.49 (d, J = 8.4 Hz, 1H), 7.11 (d, J = 8.4 Hz, 1H), 4.06 (d, J = 6.8 Hz, 2H), 3.51 (t, J = 6 , 4 Hz, 2H), 3.03 (t, J = 8.0 Hz, 2H), 1.83 (t, J = 7.6 Hz, 2H), 1.54-1.69 (m, 3H ), 1.27-1.48 (br, 15H), 0.67-0.71 (m, 2H), 0.43-0.46 (m, 2H); MS. m / z 376.2, [M + H] ⁺ .

11- (5-chloro-8- (cyclopropylmethoxy) quinolin-2-yl) undecan-1-ol (F11)

YD: 34%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.41 (d, J = 8.8 Hz, 1H), 7.43 (d, J = 2.4 Hz 1H), 7.41 (d, J = 2.4 Hz, 1H), 6.97 (d, J = 8.4 Hz, 1H), 4.09 (d, J = 7.2 Hz, 2H), 3.63 (t, J = 6, 4 Hz, 2H), 3.05 (t, J = 8.0 Hz, 2H), 1.83 (t, J = 7.6 Hz, 2H), 1.54-1.69 (m, 3H) 1.27-1.48 (br, 15H); 0.67-0.71 (m, 2H); 0.43-0.46 (m, 2H); MS. m / z 426.2, [M + Na] ⁺ .

15- (5-chloro-8- (cyclopropylmethoxy) quinolin-2-yl) pentadecan-1-ol (F12)

YD: 28%. ¹ H NMR (400 MHz, d4-MeOD + CDCl ₃ ) δ 8.47 (d, J = 8.8 Hz, 1H), 7.54 (d, J = 8.8 Hz, 1H), 7.48 (d, J = 8.4 Hz, 1H), 7.10 (d, J = 8.4 Hz, 1H), 4.06 (d, J = 6.8 Hz, 2H), 3.52 (t , J = 6.8 Hz, 2H), 3.02 (t, J = 7.6 Hz, 2H), 1.79 (quin, J = 7.6 Hz, 2H), 1.46-1.52 (m, 2H), 1.25-1.44 (br, 24H), 0.65-0.69 (m, 2H), 0.41-0.43 (m, 2H); MS. m / z 460.3, [M + Na] ⁺ .

11- (5-bromo-8- (cyclopropylmethoxy) quinolin-2-yl) undecan-1-ol (F13)

YD: 35%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.42 (d, J = 8.8 Hz, 1H), δ 7.67 (d, J = 8.4 Hz, 1H), 7.53 (d , J = 8.8 Hz, 1H), 7.06 (d, J = 8.4 Hz, 1H), 4.05 (d, J = 7.2 Hz, 2H), 3.51 (t, J = 6.4 Hz, 2H), 3.02 (t, J = 8.0 Hz, 2H), 1.77 (quin, J = 7.6 Hz, 2H), 1.46-1.52 (m , 3H), 1.28-1.44 (m, 15H), 0.65-0.70 (m, 2H), 0.42-0.45 (m, 2H); MS. m / z 470.2, [M + Na] ⁺ .

11- (5,7-dichloro-8- (cyclopropylmethoxy) quinolin-2-yl) undecan-1-ol (F14)

YD: 53%. ¹ Η NMR (400 MHz, d4-MeOD) δ 8.47 (d, J = 8.8 Hz, 1H), δ 7.67 (s, 1H), 7.53 (d, J = 8.8 Hz , 1H), 7.06 (d, J = 8.4 Hz, 1H), 4.23 (d, J = 7.2 Hz, 2H), 3.53 (t, J = 6.4 Hz, 2H ), 3.02 (t, J = 7.6 Hz, 2H), 1.86 (quin, J = 7.2 Hz, 2H), 1.48-1.53 (m, 2H), 1.29 -1.38 (m, 16H), 0.62 (dd, J = 12.8, 5.2 Hz, 2H); 0.31 (dd, J = 10.8, 5.2 Hz, 2H); MS. m / z 460.2, [M + Na] ⁺ .

Example 5 - Preparation of (5,7-dichloro-8-hydroxyquinol-2-yl) alkyl alcohol

Reagents and conditions: (a) NCS, CHCl ₃ , room temperature, 48 h.

Method: N-chlorosuccinimide (0.3 g, 2.25 mmol) was added to a stirred solution of compounds B in CHCl ₃ (20 ml) over 48 hours. The reaction mixture was poured into crushed ice and extracted with CH ₂ Cl ₂ (20 ml X 2). The extract was purified by column chromatography with Hex / EA (3: 1) and recrystallized to give a compound (0.18 g, 49%).

5,7-dichloro-2- (11-hydroxyundecyl) quinolin-8-ol (G1)

YD: 49%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.38 (d, J = 8.8 Hz, 1H), 7.51 (s, 1H), 7.42 (d, J = 8.8 Hz, 1H ), 3.63 (t, J = 6.8 Hz, 2H), 3.00 (t, J = 7.6 Hz, 2H), 1.82 (quin, J = 7.2 Hz, 2H), 1.56 (quin, J = 7.6 Hz, 2H); 1.27-1.38 (br, 15H); MS. m / z 382.0, [M-H] ⁺ .

Example 6 - Preparation of (5-chloro-8-methoxyquinol-2-yl) alkyl alcohol or alkyl acetate

Reagents and conditions: (a) HCl, ICl ₃ , ice-cold HOAc, Н ₂ О, 6 h, room temperature. Method: To the (8-methoxyquinolin-2-yl) -olam substituted with a different long chain (1.0 eq.), Conc. HCl (0.5 ml / mmol) at room temperature, and the reddish-yellow mixture was stirred for 5 minutes. To this mixture was added dropwise a 30 solution of ICl ₃ (1.5 eq.) In conc. HCl (2 ml). The yellow sticky mixture was stirred at room temperature for 6 hours. Water was added to it and separated by EA. The organic layer was washed with brine, dried on anhydrous MgSO ₄ and filtered, after which the solvent was removed, the resulting oily residue was purified by flash column chromatography using CHCl ₃ to give compounds H1 to H5.

10- (5-Chloro-8-methoxyquinolin-2-yl) decan-1-ol (H1a) and 10- (5-chloro-8-methoxyquinolin-2-yl) decyl ester of acetic acid (H1b).

YD: 61% and 10%. H1a: ¹ H NMR (200 MHz, CDCl ₃ ) 08.41 (d, J = 8.68 Hz, 1H), 7.42 (dd, J = 8 Hz, J = 2 Hz, 2H), 6.91 (d, J = 8 Hz, 1H), 4.03 (s, 3H), 3.59 (t, J = 6 Hz, 2H), 3.59 (t, J = 4 Hz, 2H), 1, 73 (m, 2H), 1.48 (m, 2H), 1.25 (br, 12H); High resolution mass spectrometry (E1): Calculated for C ₂₀ H ₂₈ ClNO ₂ : 349.1803, Found: 349.1781. H1b: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.41 (d, J = 8 Hz, 1H), 7.42 (dd, J = 8 Hz, J = 4 Hz, 2Η), 6.92 ( d, J = 8 Hz, 1H), 4.06 (t, J = 8 Hz, 2H), 4.02 (s, 3H), 3.03 (t, J = 8 Hz, 2H), 2.02 (s, 3H), 1.79 (m, 2H), 1.59 (m, 2H), 1.40 (m, 2H), 1.23 (br, 12H); High resolution mass spectrometry (FAB, M + H): Calculated for C ₂₂ H ₃₁ ClNO ₃ 392.1992, Found 392.1983.

11- (5-Chloro-8-methoxyquinolin-2-yl) undecan-1-ol (H2a) and 11- (5-chloro-8-methoxyquinolin-2-yl) undecyl acetic acid ester (H2b)

YD: 60% and 12%. H2a: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.43 (d, J = 8.72 Hz, 1H), 7.44 (dd, J = 13.5 Hz, J = 5.3 Hz, 2Η ), 6.94 (d, J = 8.3 Hz, 1H), 4.05 (s, 3H), 3.62 (t, J = 6.6 Hz, 2H), 3.07 (t, J = 5.2 Hz, 2H), 1.80 (m, 2H), 1.54 (m, 2H), 1.39 (m, 2H), 1.26 (br, 12H); High resolution mass spectrometry (EI): Calculated for C ₂₁ H ₃₀ ClNO ₂ 363.1960, Found 363.1941. H2b: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.41 (d, J = 8.6 Hz, 1H), 7.42 (dd, J = 8.3 Hz, J = 3.8 Hz, 2H ), 6.9l (d, J = 8.4 Hz, 1H), 4.06 (t, J = 7.8 Hz, 2H), 4.02 (s, 3H), 3.02 (t, J = 7.8 Hz, 2H), 2.01 (s, 3H), 1.78 (m, 2H), 1.58 (m, 2H), 1.39 (m, 2H), 1.22 (br , 12H); High Resolution Mass Spectrometry (EI): Calculated for C ₂₃ H ₃₂ ClNO ₃ 405.2065, Found 405.2044.

12- (5-Chloro-8-methoxyquinolin-2-yl) dodecan-1-ol (H3a) and 12- (5-chloro-8-methoxyquinolin-2-yl) dodecyl ester of acetic acid (H3b)

YD: 57% and 27%. H3a: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.46 (d, J = 8.6 Hz, 1H), 7.44 (dd, J = 8.3 Hz, J = 6.9 Hz, 2H ), 6.94 (d, J = 8.4 Hz, 1H), 4.04 (s, 3H), 3.59 (t, J = 6.6 Hz, 2H), 3.11 (t, J = 7.8 Hz, 2H), 1.78 (m, 2H), 1.50 (m, 2H), 1.40 (m, 2H), 1.23 (br, 14H); High Resolution Mass Spectrometry (EI): Calculated for C ₂₂ H ₃₂ ClNO ₂ 377.2116, Found 377.2106. H3b: ¹ H NMR (200 MHz, CDCl ₃ ) δ 8.38 (d, J = 8.7 Hz, 1H), 7.40 (d, J = 8.6 Hz, 2H), 6.88 (d , J = 8.4 Hz, 1H), 4.03 (t, J = 7.8 Hz, 2H), 4.01 (s, 3H), 3.02 (t, J = 7.8 Hz, 2H ), 1.99 (s, 3H), 1.76 (m, 2H), 1.59 (m, 2H), 1.20 (br, 16H); High resolution mass spectrometry (FAB, M + H): Calculated for C ₂₄ H ₃₅ ClNO ₃ 420,2305, Found 420,2310.

13- (5-chloro-8-methoxyquinolin-2-yl) tridecan-1-ol (H4a) and 13- (5-chloro-8-methoxyquinolin-2-yl) tridecyl acetic acid ester (H4b)

YD: 64% and 14%. H4a: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.46 (d, J = 8.6 Hz, 1H), 7.45 (dd, J = 8.3 Hz, J = 6.9 Hz, 2H) , 6.94 (d, J = 8.4 Hz, 1H), 4.04 (s, 3H), 3.59 (t, J = 6.6 Hz, 2H), 3.11 (t, J = 7.8 Hz, 2H), 1.78 (m, 2H), 1.50 (m, 2H), 1.40 (m, 2H), 1.23 (br, 16H); Mass spectrometry is a high-resolution (EI): Calcd for C ₂₃ H ₃₄ ClNO ₂ 391.2273, found 391.2249. H4b: ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.38 (d, J = 8.6 Hz, 1H), 7.40 (dd, J = 8.5 Hz, J = 5.8 Hz, 2H ), 6.89 (d, J = 8.4 Hz, 1H), 4.01 (t, J = 9.6 Hz, 2H), 4.00 (s, 3H), 3.00 (t, J = 7.9 Hz, 2H), 1.99 (s, 3H), 1.75 (m, 2H), 1.58 (m, 2H), 1.38 (m, 2H), 1.22 (br , 16H); High resolution mass spectrometry (FAB, M + H): Calculated for C ₂₅ H ₃₇ ClNO ₃ 434.2462, Found 434.2459.

Example 7 - Preparation of (8-hydroxyquinol-4-yl) - or (8-alkoxyquinol-4-yl) alkyl alcohols

Reagents and conditions: (a) methyl vinyl ketone, HCl, reflux, (b) MeI, K ₂ CO ₃ , acetone, room temperature, 8 hours; EtI or 2-bromopropane or methylene cyclopropyl bromide, K ₂ CO ₃ , DMF, 60 ° C, (c) 1) LHMDS, THF, 0 ° C, 1 h; 2) Br (CH ₂ ) _n-1 OH, room temperature, (d) BnBr, KOH, EtOH, reflux, (e) Н ₂ , Pd / C, MeOH, room temperature, 24 h.

Method: Intermediate INT 1 was synthesized via ring closure of 2-aminophenol reacted with methyl vinyl ketone. INT 1 was reacted with various alkyl halides to give 8-alkoxy-4-methylquinoline derivatives as intermediates. The corresponding Br (CH ₂ ) _n-1 OH was reacted with intermediates to synthesize

rows of compounds J and I. The protecting group J was removed by hydrogenation (the method is illustrated in example 1) to obtain compound K.

11- (8-methoxyquinolin-4-yl) undecan-1-ol (II)

YD: 34%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.80 (dd, J = 4.4, 0.6 Hz, 1H), 7.59 (dd, J = 8.4, 0.8 Hz, 1H) , 7.44-7.49 (m, 1H), 7.03 (d, J = 7.6 Hz, 1H), 4.08 (s, 3H), 3.63 (t, J = 6.8 Hz, 2H), 3.03 (t, J = 7.6 Hz, 2H), 1.74 (quin, J = 7.6 Hz, 2H), 1.55 (quin, J = 7.2 Hz, 2H), 1.23-1.45 (br, 15H); MS. m / z 329.9, [M + H] ⁺ .

11- (8-ethoxyquinolin-4-yl) undecan-1-ol (12)

YD: 42%. H NMR (400 MHz, d4-MeOD) δ 8.66 (d, J = 8.4 Hz, 1H), 7.64 (d, J = 8.4 Hz, 1H), 7.51 (t, J = 8.0 Hz, 1H), 7.37 (d, J = 8.4 Hz, 1H), 7.15 (d, J = 7.6 Hz, 1H), 4.27 (q, J = 6 , 8 Hz, 2H), 3.52 (t, J = 6.8 Hz, 2H), 3.08 (d, J = 7.6 Hz, 2H), 1.75 (quin, J = 7.6 Hz, 2H), 1.50-1.57 (m, 5H), 1.21-1.49 (br, 15H); MS. m / z 366.2, [M + Na] ⁺ .

11- (8-isopropoxyquinolin-4-yl) undecan-1-ol (13)

YD: 48%. ¹ Η NMR (400 MHz, d4-MeOD) δ 8.65 (d, J = 8.4 Hz, 1H), 7.63 (d, J = 7.6 Hz, 1H), 7.51 (d, J = 8.0 Hz, 1H), 7.35 (d, J = 4.4 Hz, 1H), 7.17 (d, J = 8.0 Hz, 1H), 4.84 (br, 1H) 3.52 (t, J = 6.4 Hz, 2H), 3.07 (d, J = 7.6 Hz, 2H), 1.74 (br, 2H), 1.43-1.50 ( br, 9H); 1.29-1.34 (br, 14H); MS. m / z 380.3, [M + Na] ⁺ .

11- (8- (cyclopropylmethoxy) quinolin-4-yl) undecan-1-ol (14)

YD: 53%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.66 (d, J = 8.4 Hz, 1H), 7.63 (d, J = 8.4 Hz, 1H), 7.49 (t, J = 8.4 Hz, 1H), 7.36 (d, J = 4.8 Hz, 1H), 7.13 (d, J = 7.6 Hz, 1H), 4.03 (d, J = 6.8 Hz, 1H), 3.52 (t, J = 6.8 Hz, 2H), 3.06 (d, J = 7.6 Hz, 2H), 1.69-1.75 (m, 2H), 1.28-1.52 (br, 18H), 0.65-0.68 (m, 2H), 0.42-0.43 (m, 2H); MS. m / z 392.2 [M + Na] ⁺ .

11- (8- (benzyloxy) quinolin-4-yl) undecan-1-ol (J1)

YD: 46%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.66 (d, J = 8.4 Hz, 1H), 7.64 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 7.2 Hz, 2H), 7.45 (t, J = 8.0 Hz, 1H), 7.30-7.38 (m, 3H), 7.26-7.28 (m, 1H ), 7.17 (d, J = 7.6 Hz, 1H), 5.37 (s, 2H), 3.52 (t, J = 6.4 Hz, 2H), 3.06 (t, J = 8 Hz, 2H), 1.73 (q, J = 7.6 Hz, 2H), 1.50 (t, J = 7.2 Hz, 2H), 1.28-1.48 (m, 15H ); MS. m / z 428.3, [M + Na] ⁺ .

12- (8- (benzyloxy) quinolin-4-yl) dodecan-1-ol (J2)

YD: 46%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.67 (d, J = 4.4 Hz, 1H), 7.65 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 7.2 Hz, 2H), 7.45 (t, J = 8.0 Hz, 1H), 7.30-7.39 (m, 3H), 7.27-7.30 (m, 1H ), 7.18 (d, J = 8.0 Hz, 1H), 5.38 (s, 2H), 3.52 (t, J = 6.4 Hz, 2H), 3.08 (t, J = 7.6 Hz, 2H), 1.74 (q, J = 7.6 Hz, 2H), 1.49 (t, J = 7.2 Hz, 2H), 1.23-1.45 (m , 17H); MS. m / z 442.3, [M + Na] ⁺ .

4- (11-hydroxyundecyl) quinolin-8-ol (K1)

YD: 84%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.63 (d, J = 4.4 Hz, 1H), 7.51 (d, J = 8.4 Hz, 1H), 7.40 (t, J = 8.0 Hz, 1H), 7.28 (d, J = 4.0 Hz, 1H), 7.06 (d, J = 7.6 Hz, 1H), 3.51 (t, J = 6.8 Hz, 2H), 3.02 (t, J = 8.0 Hz, 2H), 1.71 (t, J = 7.6 Hz, 2H), 1.50 (quin, J = 6, 8 Hz, 2H), 1.12-1.31 (br, 15H); MS. m / z 316.2, [M + H] ⁺ .

4- (12-hydroxydodecyl) quinolin-8-ol (K2)

YD: 86%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.52 (d, J = 4.4 Hz, 1H), 7.36 (dd, J = 8.4, 0.8 Hz, 1H), 7.31 ( d, J = 7.6 Hz, 1H), 7.13 (d, J = 4.4 Hz, 1H), 6.99 (dd, J = 7.6, 1.2 Hz, 1H), 3, 43 (t, J = 6.8 Hz, 2H), 2.89 (t, J = 7.6 Hz, 2H), 1.61 (quin, J = 7.6 Hz, 2H), 1.40 ( quin, J = 6.8 Hz, 2H); 1.12-1.31 (br, 17H); MS. m / z 352.2, [M + Na] ⁺ .

Example 8 - Preparation of (8-trifluoromethoxyquinol-2-yl) alkyl alcohols.

Method: The intermediate was synthesized via ring closure from 2-trifluoromethoxyaniline, which was reacted with crotonic aldehyde. The intermediate was reacted with the corresponding Br (CH ₂ ) _n-1 OH (as illustrated above) to synthesize a number of compounds L.

9- (8- (trifluoromethoxy) quinolin-2-yl) nonan-1-ol (L1)

YD: 41%. ¹ H NMR (400 MHz, CDCl ₃ ) δ8.06 (dd, J = 8.4, 1.2 Hz, 1H), 7.70 (d, J = 8.4 Hz, 1H), 7.56 ( d, J = 7.6 Hz, 1H), 7.43 (d, J = 8.0 Hz, 1H), 7.34 (dd, J = 8.4, 1.2 Hz, 1H), 3, 61 (t, J = 6.4 Hz, 2H), 3.01 (t, J = 6.4 Hz, 2H), 1.81-1.85 (br, 2H), 1.53-1.56 (br, 2H); 1.21-1.35 (m, 15H); MS. m / z 355.9, [M + H] ⁺ .

11- (8- (trifluoromethoxy) quinolin-2-yl) undecan-1-ol (L2)

YD: 41%. ¹ H NMR (400 MHz, d4-MeOD) δ8.26 (t, J = 8.0 Hz, 1H), 7.86 (d, J = 7.6 Hz, 1H), 7.64 (t, J = 7.2 Hz, 1H), 7.47-7.56 (m, 2H), 3.51 (t, J = 6.8 Hz, 2H), 2.99 (t, J = 6.4 Hz , 2H), 1.79 (quin, J = 6.8 Hz, 2H), 1.50 (quin, J = 6.8 Hz, 2H), 1.21-1.35 (m, 15H); MS. m / z 406.2, [M + N] ⁺ .

14- (8- (trifluoromethoxy) quinolin-2-yl) tetradecan-1-ol (L3)

YD: 37%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.27 (d, J = 8.4 Hz, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.65 (t, J = 7.2 Hz, 1H), 7.49-7.56 (m, 2H), 3.52 (t, J = 6.8 Hz, 2H), 3.01 (t, J = 7.6 Hz, 2H), 1.82 (quin, J = 7.2 Hz, 2H), 1.51 (quin, J = 6.8 Hz, 2H), 1.27-1.37 (m, 21H); MS. m / z 448.2, [M + Na] ⁺ .

15- (8- (trifluoromethoxy) quinolin-2-yl) pentadecan-1-ol (L4)

YD: 32%. ¹ H NMR (400 MHz, d4-MeOD + CDCl ₃ ) δ8.21 (d, J = 8.4 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.61 ( d, J = 7.6 Hz, 1H), 7.51 (d, J = 8.0 Hz, 1H), 7.46 (t, J = 8.4 Hz, 1H), 3.52 (t, J = 6.8

Hz, 2H), 2.99 (t, J = 7.6 Hz, 2H), 1.80 (quin, J = 7.6 Hz, 2H), 1.50 (quin, J = 7.2 Hz, 2H), 1.15-1.41 (br, 23H); MS. m / z 462.2, [M + Na] ⁺ .

Example 9 - Preparation of 2-N-substituted alcohol-8-hydroxyquinoline

Reagents and conditions: (a) SeO ₂ , dioxane, from 50 to 80 ° C; (b) N-methylpropargylamine or 2- (piperazin-1-yl) ethanol or NH ₂ (CH ₂ ) n-1OH, NaBH (OAc) ₃ , 1,2-dichloroethane, room temperature.

Method: A solution of 8-hydroxy-2-methylquinoline (6.0 g, 37.7 mmol) in dioxane (15 ml) was added dropwise to a stirred solution of SeO ₂ (6.3 g, 56.8 mmol) in dioxane (80 ml) at 50 ° C, and the mixture was heated to a temperature of not more than 80 ° C for an additional 20 hours. The resulting mixture was filtered. The filtrate was concentrated, and the residue was purified by column chromatography with Hex / EA = (15: 1 to 10: 1) to give 8-hydroxyquinoline-2-carboxaldehyde derivatives (2.45 g, 38%) as intermediates. The intermediate was converted to N-substituted compounds by reductive amination using an amino alcohol, aminoalkine or other heterocycles to give rows of compounds. 8-alkoxy-2-methylquinoline was oxidized to give 8-alkoxyquinoline-2-carboxaldehyde derivatives, and then the same method was used to prepare compounds from M to O.

2 - ((4- (2-hydroxyethyl) piperazin-1-yl) methyl) quinolin-8-ol (M1)

YD: 76%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.02 (d, J = 8.4 Hz, 1H), 7.43 (d, J = 8.4 Hz, 1H), 7.34 (t, J = 8.0 Hz, 1H), 7.22 (d, J = 7.6 Hz, 1H), 7.10 (d, J = 6.8 Hz, 1H), 3.73 (s, 2H), 3.61 (t, J = 6.8 Hz, 2H); 2.51 (t, J = 5.6 Hz, 10H); High Resolution Mass Spectrometry (ESI): Calculated for [M + Na] ⁺ : 310.1526, Found: 310.1527.

2- (4 - ((5-chloro-8-methoxyquinolin-2-yl) methyl) piperazin-1-yl) ethanol (M2)

YD: 76%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.23 (d, J = 8.8 Hz, 1H), 7.59 (d, J = 8.8 Hz, 1H), 7.21 (d, J = 8.4 Hz, 1H), 6.68 (d, J = 8.8 Hz, 1H), 3.81 (s, 3H), 3.72 (s, 2H), 3.44 (t, J = 4.8 Hz, 2H); 2.35-2.38 (m, 10H); MS. m / z 336.1, [M + H] ⁺ .

2- (4 - ((5-chloro-8-ethoxyquinolin-2-yl) methyl) piperazin-1-yl) ethanol (M3)

YD: 53%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.36 (d, J = 8.8 Hz, 1H), 7.68 (d, J = 8.4 Hz, 1H), 7.34 (d, J = 8.4 Hz, 1H), 6.83 (d, J = 8.4 Hz, 1H), 4.18 (q, J = 6.8 Hz, 3H), 3.84 (s, 2H), 3.54 (t, J = 5.2 Hz, 2H); 2.45-2.50 (br, 10H); 1.49 (t, J = 6.8 Hz, 3H); MS. m / z 350.1, [M + H] ⁺ .

2- (4 - ((5-chloro-8-isopropoxyquinolin-2-yl) methyl) piperazin-1-yl) ethanol (M4)

YD: 61%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.52 (d, J = 8.8 Hz, 1H), 7.81 (d, J = 8.8 Hz, 1H), 7.53 (d, J = 8.4 Hz, 1H), 7.14 (d, J = 8.4 Hz, 1H), 4.87 (m, 1H), 3.89 (s, 2H), 3.67 (t, J = 6.0 Hz, 2H), 2.54-2.62 (br, 10H), 1.45 (t, J = 6.0 Hz, 6H); MS. m / z 364.1, [M + H] ⁺ .

2- (4 - ((5-chloro-8- (cyclopropylmethoxy) quinolin-2-yl) methyl) piperazin-1-yl) ethane (M5)

YD: 76%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.40 (d, J = 8.4 Hz, 1H), 7.71 (d, J = 8.8 Hz, 1H), 7.42 (d, J = 8.4 Hz, 1H), 6.99 (d, J = 8.4 Hz, 1H), 3.97 (d, J = 6.8 Hz, 2H), 3.84 (s, 2H) 3.65 (t, J = 6.0 Hz, 2H), 3.44 (t, J = 4.8 Hz, 2H), 2.56 (br, 8H), 2.51 (t, J = 4.8 Hz, 2H), 1.37-1.43 (m, 1H), 0.62-0.66 (m, 2H), 0.37-0.40 (m, 2H); MS. m / z 376.2, [M + H] ⁺ .

2- (4 - ((5,7-dichloro-8-methoxyquinolin-2-yl) methyl) piperazin-1-yl) ethanol (M6)

YD: 39%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.53 (d, J = 8.8 Hz, 1H), 7.80 (d, J = 8.8 Hz, 1H), 7.70 (s, 1H), 4.11 (s, 3H), 3.89 (s, 2H), 3.67 (t, J = 6.0 Hz, 2H), 2.63 (br, 8H), 2.55 ( t, J = 6.0 Hz, 2H); 1.93 (s, 1H); MS. m / z 370.1, [M + H] ⁺ .

2- (4 - ((5,7-dichloro-8- (cyclopropylmethoxy) quinolin-2-yl) methyl) piperazin-1-yl) ethanol (M7)

YD: 82%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.43 (d, J = 8.8 Hz, 1H), 7.71 (d, J = 8.8 Hz, 1H), 7.58 (s, 1H ), 4.22 (d, J = 7.2 Hz, 2H), 3.88 (s, 2H) 3.61 (t, J = 6.4 Hz, 2H), 2.56 (t, J = 5.2 Hz, 10H), 1.41-1.44 (m, 1H), 0.57-0.62 (m, 2H), 0.33-0.37 (m, 2H); MS. m / z 410.1, [M + Na] ⁺ .

2 - ((methyl (prop-2-ynyl) amino) methyl) quinolin-8-ol (N1)

YD: 49%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.08 (d, J = 8.4 Hz, 1H), 7.55 (d, J = 8.4 Hz, 1H), 7.40 (t, J = 8.0 Hz, 1H), 7.28 (d, J = 8.0 Hz, 1H), 7.15 (d, J = 7.6 Hz, 1H), 3.90 (s, 2H), 3.41 (d, J = 2.0 Hz, 2H), 2.39 (s, 3H), 2.31 (d, J = 2.0 Hz, 1H); MS. m / z 249.1, [M + H] ⁺ .

5-chloro-2 - ((methyl (prop-2-ynyl) amino) methyl) quinolin-8-ol (N2)

YD: 38%. ¹ Η NMR (400 MHz, CDCl ₃ ) δ 8.47 (d, J = 8.4 Hz, 1H), 7.71 (d, J = 8.8 Hz, 1H), 7.47 (d, J = 8.0 Hz, 1H), 7.08 (d, J = 8.4 Hz, 1H), 3.93 (s, 2H), 3.42 (d, J = 2.0 Hz, 2H), 2.40 (s, 3H); 2.31 (t, J = 2.0 Hz, 1H); MS. m / z 261.0, [M + H] ⁺ .

N - ((5-chloro-8-methoxyquinolin-2-yl) methyl) -N-methylprop-2-in-1-amine (N3)

YD: 52%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.48 (d, J = 8.8 Hz, 1H), 7.80 (d, J = 8.8 Hz, 1H), 7.46 (d, J = 8.4 Hz, 1H), 6.93 (d, J = 8.4 Hz, 1H), 4.05 (s, 3H), 4.00 (s, 2H), 3.42 (d, J = 2.0 Hz, 2H), 2.37 (s, 3H), 2.27 (t, J = 2.0 Hz, 1H), MS. m / z 297.0, [M + Na] ⁺ .

N - ((5-chloro-8-ethoxyquinolin-2-yl) methyl) -N-methylprop-2-in-1-amine (N4)

YD: 64%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.48 (d, J = 8.8 Hz, 1H), 7.79 (d, J = 8.8 Hz, 1H), 7.46 (d, J = 8.8 Hz, 1H), 6.96 (d, J = 8.4 Hz, 1H), 4.32 (t, J = 6.8 Hz, 2H), 4.01 (s, 2H), 3.45 (d, J = 2.0 Hz, 2H), 2.41 (s, 3H), 2.28 (t, J = 2.0 Hz, 1H), 1.59 (t, J = 6 8 Hz, 3H); MS. m / z 289.1, [M + H] ⁺ .

N - ((5-chloro-8-isopropoxyquinolin-2-yl) methyl) -N-methylprop-2-in-1-amine (N5)

YD: 76%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.47 (d, J = 8.8 Hz, 1H), 7.73 (d, J = 8.8 Hz, 1H), 7.46 (d, J = 8.0 Hz, 1H), 7.03 (d, J = 8.4 Hz, 1H), 4.80 (m, 1H), 3.99 (s, 2H), 3.44 (d, J = 2.4 Hz, 2H), 2.41 (s, 3H), 2.28 (t, J = 2.4 Hz, 1H), 1.48 (d, J = 6.4 Hz, 6H); MS. m / z 303.1, [M + H] ⁺ .

N - ((5-chloro-8- (cyclopropylmethoxy) quinolin-2-yl) methyl) -N-methylprop-2-in-1-amine (N6)

YD: 58%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.48 (d, J = 8.4 Hz, 1H), 7.77 (d, J = 8.8 Hz, 1H), 7.45 (d, J = 8.4 Hz, 1H), 6.98 (d, J = 8.4 Hz, 1H), 4.09 (d, J = 7.2 Hz, 2H), 4.01 (s, 2H), 3.45 (d, J = 2.0 Hz, 2H), 2.41 (s, 3H), 2.28 (t, J = 2.0 Hz, 1H), 1.42 ~ 1.50 (m , 1H); 0.65-0.70 (m, 2H); 0.42-0.45 (m, 2H); MS. m / z 337.1, [M + Na] ⁺ .

N - ((5,7-dichloro-8-methoxyquinolin-2-yl) methyl) -N-methylprop-2-in-1-amine (N7)

YD: 58%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.47 (d, J = 8.8 Hz, 1H), 7.74 (d, J = 8.8 Hz, 1H), 7.60 (s, 1H ), 4.20 (s, 3H), 3.99 (s, 2H), 3.43 (d, J = 2.0 Hz, 2H), 2.41 (s, 3H), 2.29 (t , J = 2.0 Hz, 1H); MS. m / z 309.0, [M + H] ⁺ .

N - ((5,7-dichloro-8- (cyclopropylmethoxy) quinolin-2-yl) methyl) -N-methylprop-2-in-1-amine (N8)

YD: 76%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.45 (d, J = 8.8 Hz, 1H), 7.71 (d, J = 8.8 Hz, 1H), 7.59 (s, 1H ), 4.25 (d, J = 7.6 Hz, 2H), 3.95 (s, 2H), 3.40 (d, J = 2.0 Hz, 2H), 2.40 (s, 3H ), 2.28 (t, J = 2.0 Hz, 1H), 1.41-1.45 (m, 1H), 0.57-0.62 (m, 2H), 0.36 (dd, J = 10.0, 4.8 Hz, 2H); MS. m / z 371.0, [M + Na] ⁺ .

8 - ((5-chloro-8-methoxyquinolin-2-yl) methylamino) octan-1-ol (O1)

YD: 44%. 1 H NMR (400 MHz, d4-MeOD) δ 8.55 (d, J = 8.8 Hz, 1H), 7.69 (d, J = 8.8 Hz, 1H), 7.58 (d, J = 8.4 Hz, 1H), 7.16 (d, J = 8.4 Hz, 1H), 4.07 (s, 5H), 3.50 (t, J = 6.8 Hz, 2H), 2.63 (t, J = 7.2 Hz, 2H), 1.56 (quin, J = 7.2 Hz, 2H), 1.50 (quin, J = 6.8 Hz, 2H), 1, 29-1.32 (br, 10H); MS. m / z 351.2, [M + H] ⁺ .

8 - ((5-chloro-8-ethoxyquinolin-2-yl) methylamino) octan-1-ol (O2)

YD: 41%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.51 (d, J = 8.8 Hz, 1H), 7.66 (d, J = 8.4 Hz, 1H), 7.53 (d, J = 8.4 Hz, 1H), 7.12 (d, J = 8.4 Hz, 1H), 4.29 (q, J = 6.8 Hz, 2H), 4.07 (s, 2H) 3.51 (t, J = 6.8 Hz, 2H), 2.64 (t, J = 7.2 Hz, 2H), 1.47-1.58 (m, 7H), 1.31 ( br, 9H); MS. m / z 365.2, [M + H] ⁺ .

8 - ((5-chloro-8-isopropoxyquinolin-2-yl) methylamino) octan-1-ol (O3)

YD: 31%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.55 (d, J = 8.8 Hz, 1H), 7.66 (d, J = 8.8 Hz, 1H), 7.56 (d, J = 8.4 Hz, 1H), 7.19 (d, J = 8.4 Hz, 1H), 4.89 (m, 1H), 4.15 (s, 2H), 3.52 (t, J = 6.4 Hz, 2H), 2.71 (t, J = 7.2 Hz, 2H), 1.59 (quin, J = 6.8 Hz, 2H) 1.46-1.50 (m, 8H), 1.33 (br, 9H); MS. m / z 379.2, [M + H] ⁺ .

8 - ((5-chloro-8- (cyclopropylmethoxy) quinolin-2-yl) methylamino) octan-1-ol (O4)

YD: 29%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.54 (d, J = 8.4 Hz, 1H), 7.67 (d, J = 8.8 Hz, 1H), 7.54 (d, J = 8.4 Hz, 1H), 7.15 (d, J = 8.4 Hz, 1H), 4.09 (s + d, J = 6.8 Hz, 4H), 3.51 (t, J = 6.8 Hz, 2H), 2.67 (t, J = 7.2 Hz, 2H), 1.59 (quin, J = 7.2 Hz, 2H), 1.43-1.51 (m , 3H), 1.29-1.42 (br, 10H), 0.66-0.89 (m, 2H), 0.44 (dd, J = 10.4, 4.8 Hz, 2H); MS. m / z 391.2, [M + H] ⁺ .

8 - ((5,7-dichloro-8-methoxyquinolin-2-yl) methylamino) octan-1-ol (O5)

YD: 37%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.54 (d, J = 8.8 Hz, 1H), 7.71 (s, 1H), 7.65 (d, J = 8.8 Hz, 1H ), 4.14 (s, 3H), 4.12 (s, 2H), 3.52 (t, J = 6.8 Hz, 2H), 2.70 (t, J = 7.2 Hz, 2H ), 1.60 (quin, J = 6.8 Hz, 2H), 1.50 (m, 2H), 1.33 (br, 9H); MS. m / z 385.1, [M + H] ⁺ .

8 - ((5,7-dichloro-8- (cyclopropylmethoxy) quinolin-2-yl) methylamino) octan-1-ol (O6)

YD: 56%. ¹ H NMR (400 MHz, d4-MeOD) δ 8.51 (d, J = 8.4 Hz, 1H), 7.69 (s, 1H), 7.61 (d, J = 8.8 Hz, 1H ), 4.22 (d, J = 7.2 Hz, 2H), 4.10 (s, 2H), 3.52 (t, J = 6.8 Hz, 2H), 2.68 (t, J = 7.2 Hz, 2H), 1.59 (quin, J = 7.2 Hz, 2H), 1.51 (quin, J = 6.8 Hz, 2H), 1.28-1.42 (br 11H), 0.55-0.60 (m, 2H), 0.30-0.33 (m, 2H); MS. m / z 425.2, [M + H] ⁺ .

6- (bis ((8-methoxyquinolin-2-yl) methyl) amino) hexan-1-ol (P1)

¹ H NMR (400 MHz, d4-MeOD) δ 8.18 (d, J = 8.4 Hz, 2H), 7.80 (d, J = 8.4 Hz, 2H), 7.44 (t, J = 8.0 Hz, 2H), 7.38 (d, J = 8.0 Hz, 2H), 7.13 (d, J = 7.2 Hz, 2H), 4.02 (s, 6H), 3.99 (s, 4H), 3.40 (t, J = 6.8 Hz, 2H), 2.59 (t, J = 6.8 Hz, 2H), 1.56 (quin, J = 6 8 Hz, 2H), 1.41 (quin, J = 6.8 Hz, 2H), 1.27 (quin, J = 7.6 Hz, 2H), 1.18 (quin, J = 6.8 Hz, 2H); MS. m / z 482.3, [M + Na] ⁺ .

In FIG. 1A shows β-amyloid aggregation inhibited by C12, in the presence or absence of zinc ions, using a microscopy analysis after staining with Congo red. In FIG. 1B and FIG. 2 that C12 destroys preformed β-amyloid aggregates. In FIG. 3A-B show that compounds C12, CQ, and intermediate C12 protect neuron cells from zinc-induced β-amyloid fibrils. Only compound C12 was effective against zinc-free aggregates (FIG. 3B). In FIG. Figure 4 shows the induction of axon overgrowth caused by compounds B3, C3, and D3, respectively, on undifferentiated PC12 cells. In FIG. 5 shows the expression of GAP43 increased due to quinoline derivatives. In FIG. Figure 6 shows the improvement in learning ability in memory-deficient mice affected by β-amyloid fibrils due to compounds C12 and B3. C12 and B3 (10 mg / kg) increase the residence time of mice infected with β-amyloid fibrils on a rod in a test on a rotating rod. In FIG. 7A-D presents an improvement in the learning ability of memory-deficient mice affected by β-amyloid fibrils in the Morris water maze test due to compound C12. Mice were evaluated by the total duration of movement (Fig. 7A.) And the total duration of the distance (Fig. 7B.) Before climbing onto a hidden platform; and also quantitatively evaluated the appearance in the target area (Fig. 7C.) indicating the relative time (compared to the total time during the swimming process) before entering the area around the hidden platform; as well as for the average swimming speed (Fig. 7D), in order to distinguish between increased memory and increased motor activity. In FIG. Figure 8 shows an increase in GAP43 and a decrease in β-amyloid fibrils in memory deficient mice affected by β-amyloid fibrils through compound C12.

The preceding description of exemplary embodiments of the present invention was presented for purposes of illustration and description only and is not intended to be exhaustive or to limit the present invention to the exact disclosed forms. In light of the foregoing disclosure, many modifications and variations are possible.

Embodiments and examples have been selected and described to explain the principles of the present invention and their practical application so that other specialists in this field could apply the present invention and various implementations and various modifications suitable for the particular intended application. Alternative embodiments will be apparent to those skilled in the art to which the present invention relates, without departing from its spirit and scope. Accordingly, the scope of the present invention is determined by the appended claims, and not by the foregoing description and exemplary embodiments described herein.

Some references, which may include patents, patent applications, and various publications, are set forth and discussed in the description of the present invention. The citation and / or discussion of such references is provided only to clarify the description of the present invention and is not an acknowledgment that any such reference is a “prior art” of the invention described herein. All references cited and discussed in the present description are fully incorporated into this application by reference, and to the same extent as if each link was individually incorporated by reference.

Claims (186)

1. The compound of formula (I) or its pharmaceutically acceptable salt:

(I) where R ¹ represents hydrogen, (C ₁ -C ₃ ) alkyl, (C ₁ ) alkylene (C ₃ ) cycloalkyl, (C ₁ ) haloalkyl or (C ₁ ) alkylene (C ₆ ) aryl; R ² represents hydrogen or halogen; R ³ represents hydrogen, halogen, (C ₁ ) alkyl or (C ₁ ) alkoxy; R ⁴ represents hydrogen, halogen, (C ₁ ) alkyl, (C ₁ ) alkoxy or (C ₁ ) haloalkyl; R ⁵ represents hydrogen; R ⁶ represents hydrogen, and R ⁷ is (C ₉ -C ₁₅ ) alkanol, (C ₁ ) alkylene piperazinyl (C ₁ -C ₂ ) alkanol, (C ₁ -C ₈ ) alkylene piperazinyl (C ₁ -C ₂ ) alkyl, (C ₁₀ -C ₁₃ ) alkylene OOCCH ₃ , (C ₁ ) alkylene (C ₁ ) alkylamino (C ₃ ) alkynyl, (C ₁ ) alkyleneamino (C ₈ ) alkanol or (C ₁ ) alkyleneamino (C ₆ ) alkanol (C ₁ ) alkylene (8-methoxyquinoline -2-yl); or (II) where R ¹ , R ² , R ³ , R ⁴ and R ^{6 are} each as described in (I) above; R ⁵ represents (C ₁₁ -C ₁₂ ) alkanol, and R ⁷ represents hydrogen. 2. The compound of formula (I) or its pharmaceutically acceptable salt

, (A) characterized in that R ¹ represents hydrogen, CH ₃ , CH ₂ CH ₃ , CH (CH ₃ ) ₂ , CH ₂ CH (CH ₂ ) ₂ , CF ₃ or benzyl; R ² represents hydrogen, F or Cl; R ³ represents hydrogen, F, Cl, CH ₃ or OCH ₃ ; R ⁴ represents hydrogen, F, Cl, Br, CH ₃ , OCH ₃ or CF ₃ ; R ⁵ represents hydrogen; R ⁶ represents hydrogen, and R ⁷ represents (CH ₂ ) ₉ OH, (CH ₂ ) ₁₀ OH, (CH ₂ ) ₁₁ OH, (CH ₂ ) ₁₂ OH, (CH ₂ ) ₁₃ OH, (CH ₂ ) ₁₄ OH, (CH ₂ ) ₁₅ OH, (CH ₂ ) ₁₀ OCOCH ₃ , (CH ₂ ) ₁₁ OCOCH ₃ , (CH ₂ ) ₁₂ OCOCH ₃ , (CH ₂ ) ₁₃ OCOCH ₃ , CH ₂ (N (CH ₂ CH ₂ ) ₂ N) CH ₂ CH ₂ OH, CH ₂ N (CH ₃ ) CH ₂ C≡CH, CH ₂ NH (CH ₂ ) ₈ OH or CH ₂ N ((CH ₂ ) ₆ OH) CH ₂ (8-methoxyquinolin-2-yl); or  (B) characterized in that R ¹ , R ² , R ³ , R ⁴ and R ^{6 are} each as described in (A) above; R ⁵ represents (CH ₂ ) ₁₁ OH or (CH ₂ ) ₁₂ OH, and R ⁷ represents hydrogen. 3. The compound according to claim 2, characterized in that R ¹ represents hydrogen, CH ₃ , CH ₂ CH ₃ , CH (CH ₃ ) ₂ , CH ₂ CH (CH ₂ ) ₂ , CF ₃ or benzyl; R ² , R ³ , R ⁴ , R ⁵ and R ⁶ each independently represents hydrogen, and R ⁷ represents (CH ₂ ) ₉ OH, (CH ₂ ) ₁₀ OH, (CH ₂ ) ₁₁ OH, (CH ₂ ) ₁₂ OH, (CH ₂ ) ₁₃ OH, (CH ₂ ) ₁₄ OH, (CH ₂ ) ₁₅ OH, CH ₂ (N (CH ₂ CH ₂ ) ₂ N) CH ₂ CH ₂ OH or CH ₂ N (CH ₃ ) CH ₂ C≡CH. 4. The compound according to claim 2, characterized in that R ¹ represents hydrogen, CH ₃ , CH ₂ CH ₃ , CH ₂ CH (CH ₂ ) ₂ or CH (CH ₃ ) ₂ ; R ² , R ³ , R ⁵ and R ⁶ each independently represents hydrogen; R ⁴ represents CH ₃ , F, Cl, Br, CF ₃ or OCH _3, and R ⁷ represents (CH ₂ ) ₉ OH, (CH ₂ ) ₁₀ OH, (CH ₂ ) ₁₁ OH, (CH ₂ ) ₁₂ OH, (CH ₂ ) ₁₃ OH, (CH ₂ ) ₁₅ OH, (CH ₂ ) ₁₀ AOCOS ₃ , (CH ₂ ) ₁₁ AOCOS ₃ , (CH ₂ ) ₁₂ AOCOS ₃ , (CH ₂ ) ₁₃ AOCOS ₃ , CH ₂ NH (CH ₂ ) ₈ OH, CH ₂ (N (CH ₂ CH ₂ ) ₂ N ) CH ₂ CH ₂ OH or CH ₂ N (CH ₃ ) CH ₂ CH≡CH. 5. The compound according to claim 2, characterized in that R ¹ represents hydrogen, CH ₃ , CH ₂ CH ₃ , CH (CH ₂ ) ₂ or CH ₂ CH (CH ₂ ) ₂ ; R ² , R ⁴ each independently represents Cl; R ³ , R ⁵ and R ⁶ each independently represents hydrogen, and R ⁷ represents (CH ₂ ) ₁₁ OH, CH ₂ NH (CH ₂ ) ₈ OH or CH ₂ N (CH ₃ ) CH ₂ C≡CH. 6. The compound according to claim 2, characterized in that R ¹ represents hydrogen, CH ₃ , CH ₂ CH ₃ , CH ₂ CH (CH ₂ ) ₂ , CH (CH ₃ ) ₂ or benzyl; R ² , R ³ , R ⁴ , R ⁶ and R ⁷ each independently represents hydrogen, and R ⁵ represents (CH ₂ ) ₁₁ OH or (CH ₂ ) ₁₂ OH. 7. The compound according to claim 2, characterized in that R ¹ represents CH ₃ ; R ² , R ⁵ and R ⁶ each independently represents hydrogen; R ³ and R ⁴ each independently represents OCH ₃ or Cl, and R ⁷ represents (CH ₂ ) ₁₁ OH. 8. The compound according to claim 2, selected from the group consisting of: 9- (8- (benzyloxy) quinolin-2-yl) nonan-1-ol, 10- (8- (benzyloxy) quinolin-2-yl) decan-1-ol, 11- (8- (benzyloxy) quinolin-2-yl) undecan-1-ol, 12- (8- (benzyloxy) quinolin-2-yl) dodecan-1-ol, 13- (8- (benzyloxy) quinolin-2-yl) tridecan-1-ol, 14 - ((8- (benzyloxy) quinolin-2-yl) tetradecan-1-ol, 15- (8- (benzyloxy) quinolin-2-yl) pentadecan-1-ol, 11- (8- (benzyloxy) -5-methylquinolin-2-yl) undecan-1-ol, 11- (8- (benzyloxy) -6-methylquinolin-2-yl) undecan-1-ol, 11- (8- (benzyloxy) -5-fluoroquinolin-2-yl) undecan-1-ol, 11- (8- (benzyloxy) -5-chloroquinolin-2-yl) undecan-1-ol, 2- (9-hydroxynonyl) quinolin-8-ol, 2- (10-hydroxydecyl) quinolin-8-ol, 2- (11-hydroxyundecyl) quinolin-8-ol, 2- (12-hydroxydodecyl) quinolin-8-ol, 2- (13-hydroxytridecyl) quinolin-8-ol, 2- (14- (hydroxytetradecyl) quinolin-8-ol, 2- (15-hydroxypentadecyl) quinolin-8-ol, 2- (11-hydroxyundecyl) -5-methylquinolin-8-ol, 2- (11-hydroxyundecyl) -6-methylquinolin-8-ol, 5-chloro-2- (11-hydroxyundecyl) quinolin-8-ol, 9- (8-methoxyquinolin-2-yl) nonan-1-ol, 10- (8-methoxyquinolin-2-yl) decan-1-ol, 11- (8-methoxyquinolin-2-yl) undecan-1-ol, 12- (8-methoxyquinolin-2-yl) dodecan-1-ol, 13- (8-methoxyquinolin-2-yl) tridecan-1-ol, 14 - ((8-methoxyquinolin-2-yl) tetradecan-1-ol, 15- (8-methoxyquinolin-2-yl) pentadecan-1-ol, 11- (8-methoxy-5-methylquinolin-2-yl) undecan-1-ol, 11- (5-fluoro-8-methoxyquinolin-2-yl) undecan-1-ol, 12- (5-fluoro-8-methoxyquinolin-2-yl) dodecan-1-ol, 9- (5-chloro-8-methoxyquinolin-2-yl) nonan-1-ol, 11- (5-chloro-8-methoxyquinolin-2-yl) undecan-1-ol, 15- (5-chloro-8-methoxyquinolin-2-yl) pentadecan-1-ol, 11- (5-bromo-8-methoxyquinolin-2-yl) undecan-1-ol, 11- (8-methoxy-5- (trifluoromethyl) quinolin-2-yl) undecan-1-ol, 11- (5,8-dimethoxyquinolin-2-yl) undecan-1-ol, 11- (8-methoxy-6-methylquinolin-2-yl) undecan-1-ol, 11- (6-fluoro-8-methoxyquinolin-2-yl) undecan-1-ol, 11- (6-chloro-8-methoxyquinolin-2-yl) undecan-1-ol, 11- (7-fluoro-8-methoxyquinolin-2-yl) undecan-1-ol, 11- (7-chloro-8-methoxyquinolin-2-yl) undecan-1-ol, 11- (5-chloro-6,8-dimethoxyquinolin-2-yl) undecan-1-ol, 11- (6-chloro-5,8-dimethoxyquinolin-2-yl) undecan-1-ol, 11- (5,7-dichloro-8-methoxyquinolin-2-yl) undecan-1-ol, 9- (8-ethoxyquinolin-2-yl) nonan-1-ol, 10- (8-ethoxyquinolin-2-yl) decan-1-ol, 11- (8-ethoxyquinolin-2-yl) undecan-1-ol, 12- (8-ethoxyquinolin-2-yl) dodecan-1-ol, 13- (8-ethoxyquinolin-2-yl) tridecan-1-ol, 14 - ((8-ethoxyquinolin-2-yl) tetradecan-1-ol, 15- (8-ethoxyquinolin-2-yl) pentadecan-1-ol, 11- (8-ethoxy-5-methylquinolin-2-yl) undecan-1-ol, 11- (8-ethoxy-5-fluoroquinolin-2-yl) undecan-1-ol, 9- (5-chloro-8-ethoxyquinolin-2-yl) nonan-1-ol, 11- (5-chloro-8-ethoxyquinolin-2-yl) undecan-1-ol, 15- (5-chloro-8-ethoxyquinolin-2-yl) pentadecan-1-ol, 11- (5-bromo-8-ethoxyquinolin-2-yl) undecan-1-ol, 11- (5,7-dichloro-8-ethoxyquinolin-2-yl) undecan-1-ol, 9- (8-isopropoxyquinolin-2-yl) nonan-1-ol, 10- (8-isopropoxyquinolin-2-yl) decan-1-ol, 11- (8-isopropoxyquinolin-2-yl) undecan-1-ol, 12- (8-isopropoxyquinolin-2-yl) dodecan-1-ol, 13- (8-isopropoxyquinolin-2-yl) tridecan-1-ol, 14 - ((8-isopropoxyquinolin-2-yl) tetradecan-1-ol, 15- (8-isopropoxyquinolin-2-yl) pentadecan-1-ol, 11- (8-isopropoxy-5-methylquinolin-2-yl) undecan-1-ol, 11- (5-fluoro-8-isopropoxyquinolin-2-yl) undecan-1-ol, 9- (5-chloro-8-isopropoxyquinolin-2-yl) nonan-1-ol, 11- (5-chloro-8-isopropoxyquinolin-2-yl) undecan-1-ol, 15- (5-chloro-8-isopropoxyquinolin-2-yl) pentadecan-1-ol, 11- (5-bromo-8-isopropoxyquinolin-2-yl) undecan-1-ol, 11- (5,7-dichloro-8-isopropoxyquinolin-2-yl) undecan-1-ol, 9- (8- (cyclopropylmethoxy) quinolin-2-yl) nonan-1-ol, 10- (8- (cyclopropylmethoxy) quinolin-2-yl) decan-1-ol, 11- (8- (cyclopropylmethoxy) quinolin-2-yl) undecan-1-ol, 12- (8- (cyclopropylmethoxy) quinolin-2-yl) dodecan-1-ol, 13- (8- (cyclopropylmethoxy) quinolin-2-yl) tridecan-1-ol, 14 - ((8- (cyclopropylmethoxy) quinolin-2-yl) tetradecan-1-ol, 15- (8- (cyclopropylmethoxy) quinolin-2-yl) pentadecan-1-ol, 11- (8- (cyclopropylmethoxy) -5-methylquinolin-2-yl) undecan-1-ol, 11- (8- (cyclopropylmethoxy) -5-fluoroquinolin-2-yl) undecan-1-ol, 9- (5-chloro-8- (cyclopropylmethoxy) quinolin-2-yl) nonan-1-ol, 11- (5-chloro-8- (cyclopropylmethoxy) quinolin-2-yl) undecan-1-ol, 15- (5-chloro-8- (cyclopropylmethoxy) quinolin-2-yl) pentadecan-1-ol, 11- (5-bromo-8- (cyclopropylmethoxy) quinolin-2-yl) undecan-1-ol, 11- (5,7-dichloro-8- (cyclopropylmethoxy) quinolin-2-yl) undecan-1-ol, 5,7-dichloro-2- (11-hydroxyundecyl) quinolin-8-ol, 10- (5-chloro-8-methoxyquinolin-2-yl) decan-1-ol, 10- (5-chloro-8-methoxyquinolin-2-yl) decyl ester of acetic acid, 11- (5-chloro-8-methoxyquinolin-2-yl) undecan-1-ol, 11- (5-chloro-8-methoxyquinolin-2-yl) undecyl ester of acetic acid, 12- (5-chloro-8-methoxyquinolin-2-yl) dodecan-1-ol, 12- (5-chloro-8-methoxyquinolin-2-yl) dodecyl ester of acetic acid, 13- (5-chloro-8-methoxyquinolin-2-yl) tridecan-1-ol, 13- (5-chloro-8-methoxyquinolin-2-yl) tridecyl ester of acetic acid, 11- (8-methoxyquinolin-4 - (- yl) undecan-1-ol, 11- (8-ethoxyquinolin-4 - (- yl) undecan-1-ol, 11- (8-isopropoxyquinolin-4 - (- yl) undecan-1-ol, 11- (8- (cyclopropylmethoxy) quinolin-4 - (- yl) undecan-1-ol, 11- (8- (benzyloxy) quinolin-4 - (- yl) undecan-1-ol, 12- (8- (benzyloxy) quinolin-4 - (- yl) dodecan-1-ol, 4 - ((11-hydroxyundecyl) quinolin-8-ol, 4 - ((12-hydroxydodecyl) quinolin-8-ol, 9- (8- (trifluoromethoxy) quinolin-2-yl) nonan-1-ol, 11- (8- (trifluoromethoxy) quinolin-2-yl) undecan-1-ol, 14 - ((8- (trifluoromethoxy) quinolin-2-yl) tetradecan-1-ol, 15- (8- (trifluoromethoxy) quinolin-2-yl) pentadecan-1-ol, 2 - ((4 - ((2-hydroxyethyl) piperazin-1-yl) methyl) quinolin-8-ol, 2- (4 - (((5-chloro-8-methoxyquinolin-2-yl) methyl) piperazin-1-yl) ethanol, 2- (4 - (((5-chloro-8-ethoxyquinolin-2-yl) methyl) piperazin-1-yl) ethanol, 2- (4 - (((5-chloro-8-isopropoxyquinolin-2-yl) methyl) piperazin-1-yl) ethanol, 2- (4 - (((5,7-dichloro-8-methoxyquinolin-2-yl) methyl) piperazin-1-yl) ethanol, 2- (4 - (((5,7-dichloro-8- (cyclopropylmethoxy) quinolin-2-yl) methyl) piperazin-1-yl) ethanol, 2 - ((methyl (prop-2-ynyl) amino) methyl) quinolin-8-ol, 5-chloro-2 - ((methyl (prop-2-ynyl) amino) methyl) quinolin-8-ol, N ((5-chloro-8-methoxyquinolin-2-yl) methyl) -N-methylprop-2-in-1-amine, N ((5-chloro-8-ethoxyquinolin-2-yl) methyl) -N-methylprop-2-in-1-amine, N ((5-chloro-8-isopropoxyquinolin-2-yl) methyl) -N-methylprop-2-yn-1-amine, N ((5-chloro-8- (cyclopropylmethoxy) quinolin-2-yl) methyl) -N-methylprop-2-yn-1-amine, N ((5,7-dichloro-8-methoxyquinolin-2-yl) methyl) -N-methylprop-2-yn-1-amine, N ((5,7-dichloro-8- (cyclopropylmethoxy) quinolin-2-yl) methyl) -N-methylprop-2-in-1-amine, 8 - ((5-chloro-8-methoxyquinolin-2-yl) methylamino) octan-1-ol, 8 - ((5-chloro-8-ethoxyquinolin-2-yl) methylamino) octan-1-ol, 8 - ((5-chloro-8-isopropoxyquinolin-2-yl) methylamino) octan-1-ol, 8 - ((5-chloro-8- (cyclopropylmethoxy) quinolin-2-yl) methylamino) octan-1-ol, 8 - ((5,7-dichloro-8-methoxyquinolin-2-yl) methylamino) octan-1-ol, 8 - ((5,7-dichloro-8- (cyclopropylmethoxy) quinolin-2-yl) methylamino) octan-1-ol and 6- (bis ((8-methoxyquinolin-2-yl) methyl) amino) hexan-1-ol. 9. The compound of formula (I) or its pharmaceutically acceptable salt according to claim 1, where R ² represents hydrogen. 10. The compound of formula (I) or a pharmaceutically acceptable salt thereof according to claim 1, wherein R ¹ is hydrogen, (C ₁ -C ₃ ) alkyl, (C ₁ ) alkylene (C ₃ ) cycloalkyl or (C ₁ ) haloalkyl. 11. A pharmaceutical composition for use in the treatment of Alzheimer's disease, traumatic brain damage and / or spinal cord injury, containing a therapeutically effective amount of a compound according to any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable diluent or carrier. 12. A method of treating Alzheimer's disease, traumatic brain damage and / or spinal cord injury, comprising administering to a patient in need thereof a pharmaceutical composition comprising a therapeutically effective amount of a compound according to any one of claims 1, 8, 9 or 10 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable diluent or carrier. 13. A method for improving the learning and / or memory ability of a patient suffering from Alzheimer's disease, comprising administering to a patient suffering from Alzheimer's disease a pharmaceutical composition comprising a therapeutically effective amount of a compound according to any one of claims 1, 8, 9 or 10, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable diluent or carrier.

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