Novel derivatives having a 1,2,3,4-tetrahydronaphthalene group or pharma- ceutically acceptable salts thereof and pharmaceutical compositions containing the same

Abstract

The present invention provides novel compounds having a 1,2,3,4-tetrahydronaphthalene group or pharmaceutically acceptable salts thereof, methods for preparing them, pharmaceutical compositions containing them, and uses thereof. The compounds having a 1,2,3,4-tetrahydronaphthalene group or pharmaceutically acceptable salts thereof according to the present invention have inhibitory activity against glucosylceramide synthase (GCS). Therefore, they can be usefully applied to the prevention or treatment of various diseases associated with GCS, such as Gaucher disease, Fabry disease, Tay-Sachs disease, and Parkinson's disease.

Description

[Technical field]

[0001] The present invention relates to a novel compound having inhibitory activity against glucosylceramide synthase (GCS), i.e., a derivative having a 1,2,3,4-tetrahydronaphthalene group or a pharma- ceutically acceptable salt thereof, a method for producing the same, a pharmaceutical composition containing the same, and use of the same. [Background technology]

[0002] Lysosomal storage diseases (LSDs) are metabolic disorders caused by genetic absence or deficiency of certain enzymes in lysosomes. LSDs cause various pathological symptoms throughout the body due to the accumulation of unmetabolized or undegraded substrates. Currently, about 50 types of LSDs are known, and they are broadly classified into diseases such as mucopolysaccaridosis, oligosaccharidosis, and sphingolipidosis depending on the substances that are accumulated.

[0003] Among diseases, sphingolipidoses, which are a type of glycolipid storage disorder related to sphingolipid metabolism, exhibit pathology due to the accumulation of various membrane sphingoglycolipids (GSLs) such as glucosylceramide, trihexosylceramide, etc. For example, when enzymes related to sphingolipid metabolism, such as beta-glucosidase and alpha-galactosidase, do not have normal activity, their substrates (e.g., glucosylceramide, trihexosylceramide, etc.) accumulate, which results in various pathologies such as Gaucher disease and Fabry disease.

[0004] There are two known types of treatment for LSD. The first method is to replace or supplement the insufficient or missing metabolic enzymes. Such enzyme replacement therapy (ERT) is safe and effective, but requires regular intravenous administration of the relevant enzyme; its dose needs to be adjusted according to the enzymatic reaction; and its cost is relatively high. In particular, it is difficult to deliver the enzyme to the nervous system, so ERT is not sufficiently effective in treating symptoms related to the nervous system. In addition, there is a problem that autoantibodies against the administered enzyme are frequently produced.

[0005] The second method is substrate reduction therapy (SRT) to inhibit the synthesis of the substrates that are to be accumulated. Glucosylceramide synthase (GCS), an enzyme involved in sphingolipid metabolism (also called "UDP-glucose:ceramide glycosyltransferase", "UDP-glucose:N-acylsphingosine D-glucosyltransferase", or "EC2.4.1.80"), is involved in the reaction of ceramide with glucose to produce glucosylceramide. The resulting glucosylceramide is converted into various GSLs. Glucosylceramide synthase (GCS) inhibitors inhibit the activity of GCS, thereby reducing the production of glucosylceramide in the body and preventing the abnormal accumulation of glycolipids (e.g., trihexosylceramide, GM1, GM2) in cells and organs.

[0006] Thus, GCS inhibitors inhibit the activity of GCS and prevent the accumulation of glycolipids, and therefore can be usefully applied in the treatment of lysosomal storage diseases, particularly glycolipid storage disorders such as GM1 gangliosidosis, Tay-Sachs disease, Sandhoff disease, Gaucher disease, Fabry disease, Niemann-Pick disease (types A and B), metachromatic leukodystrophy, and Krabbe disease. GCS inhibitors can also be used to treat secondary diseases associated with glycolipid storage, such as Niemann-Pick disease (type C), mucopolysaccharidosis, and type IV mucolipidosis (see Chen CS, et al., Abnormal transport along the lysosomal pathway in mucolipidosis, type IV disease Proc Natl Acad Sci US A. 1998 May 26;95(11):6373-8; and Goodman LA, et al., Ectopic dendrites occur only on cortical pyramidal cells containing elevated GM2 ganglioside in alpha-mannosidosis, Proc Natl Acad Sci US A. 1991 Dec 15;88(24):11330-4). It has also been reported to be useful in the treatment of diseases associated with glycolipid accumulation, such as renal hypertrophy (e.g., diabetic kidney disease); hyperglycemia or hyperinsulinemia; cancers with abnormal glycolipid synthesis; infectious diseases caused by organisms that use cell surface glycolipids as receptors; infectious diseases in which glucosylceramide synthesis is essential or important; diseases in which excessive glycolipid synthesis occurs (e.g., atherosclerosis, polycystic kidney disease, and renal hypertrophy); neurological disorders and / or damage associated with macrophage recruitment or activity (e.g., Alzheimer's disease, epilepsy, stroke, spinal cord disease, Parkinson's disease, etc.); inflammatory diseases or disorders (e.g., rheumatoid arthritis, Crohn's disease, asthma, sepsis); and diabetes and obesity (see WO2006 / 053043).And overexpression of GCS interferes with ceramide-induced apoptosis (see Liu YY, et al., Uncoupling ceramide glycosylation by transfection of glucosylceramide synthase antisense reverses adriamycin resistance, J Biol Chem. 2000 Mar 10;275(10):7138-43). Therefore, GCS inhibitors may be useful in treating proliferative diseases such as cancer by inducing apoptosis in diseased cells.

[0007] Various studies have been conducted to develop GCS inhibitors. For example, various compounds having inhibitory activity against GCS are disclosed in WO2005 / 068426, WO2006 / 053043, WO2008 / 150486, WO2009 / 117150, WO2010 / 014554, WO2014 / 043068, etc. Summary of the Invention [Problem to be solved by the invention]

[0008] The present inventors have found that a derivative having a 6,6-fused bicyclic group, i.e., a 1,2,3,4-tetrahydronaphthalene group, or a pharma- ceutically acceptable salt thereof, has excellent inhibitory activity against glucosylceramide synthase (GCS). Therefore, the derivative having a 1,2,3,4-tetrahydronaphthalene group or a pharma- ceutically acceptable salt thereof can be usefully applied to prevent or treat various diseases associated with GCS, such as Gaucher disease, Fabry disease, Tay-Sachs disease, and Parkinson's disease.

[0009] Thus, the present invention provides a derivative having a 1,2,3,4-tetrahydronaphthalene group or a pharma- ceutically acceptable salt thereof, a method for producing the same, a pharmaceutical composition containing the same, and use of the same. [Means for solving the problem]

[0010] According to one aspect of the present invention, there is provided a derivative having a 1,2,3,4-tetrahydronaphthalene group or a pharma- ceutically acceptable salt thereof.

[0011] In another aspect of the present invention, there is provided a method for producing the derivative having a 1,2,3,4-tetrahydronaphthalene group or a pharma- ceutically acceptable salt thereof.

[0012] In still another aspect of the present invention, there is provided a pharmaceutical composition comprising the above-mentioned derivative having a 1,2,3,4-tetrahydronaphthalene group or a pharma- ceutically acceptable salt thereof as an active ingredient.

[0013] Yet another aspect of the present invention provides a therapeutic method comprising administering the derivative having a 1,2,3,4-tetrahydronaphthalene group or a pharma- ceutically acceptable salt thereof.

[0014] According to yet another aspect of the present invention, there is provided use of the derivative having a 1,2,3,4-tetrahydronaphthalene group or a pharma- ceutically acceptable salt thereof for the manufacture of a medicament for inhibiting glucosylceramide synthase. Effect of the Invention

[0015] According to the present invention, it has been found that a derivative having a 6,6-fused bicyclic group, i.e., a 1,2,3,4-tetrahydronaphthalene group, or a pharma- ceutical acceptable salt thereof has excellent inhibitory activity against glucosylceramide synthase (GCS). Therefore, the compound according to the present invention or a pharma- ceutical acceptable salt thereof can be usefully applied to prevent or treat various diseases associated with GCS, such as Gaucher disease, Fabry disease, Tay-Sachs disease, and Parkinson's disease. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0016] As used herein, the term "alkyl" refers to a straight or branched chain aliphatic hydrocarbon group. For example, C 1 ~C 6Alkyl refers to a straight or branched chain aliphatic hydrocarbon having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, n-butyl, n-pentyl, n-hexyl, isopropyl, isobutyl, sec-butyl, tert-butyl, neopentyl, and isopentyl.

[0017] The term "hydroxy" refers to the group "-OH". The term "alkoxy" refers to a group formed by replacing the hydrogen atom of a hydroxyl group with an alkyl. For example, C 1 ~C 6 Alkoxy includes methoxy, ethoxy, propoxy, n-butoxy, n-pentyloxy, isopropoxy, sec-butoxy, tert-butoxy, neopentyloxy, and isopentyloxy.

[0018] The term "halogen" refers to a fluoro, bromo, chloro, or iodo group.

[0019] The term "cycloalkyl," unless otherwise specified, refers to a saturated aliphatic 3- to 10-membered ring, preferably 3- to 7-membered ring. Typical cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like.

[0020] The term "aryl" refers to an organic group derived from an aromatic hydrocarbon by removing one hydrogen atom from the aromatic hydrocarbon, and includes a monocyclic or polycyclic condensed system such as a 5-14 membered substituted or unsubstituted ring, and a form in which multiple aryls are linked by a single bond. Examples of "aryl" include, but are not limited to, phenyl, naphthyl, biphenyl, terphenyl, anthryl, indenyl, fluorenyl, phenanthryl, triphenylenyl, pyrenyl, perylenyl, chrysenyl, naphthacenyl, and fluoranthenyl.

[0021] The term "heteroaryl" refers to a 5- to 12-membered aromatic group having 1 to 3 heteroatoms selected from the group consisting of nitrogen (N), oxygen (O), and sulfur (S), including a 5- or 6-membered monocyclic heteroaryl group and a bicyclic heteroaryl group formed by condensing a 5- or 6-membered monocyclic heteroaryl group with a benzene ring or a pyridine ring. The term "heterocycle" refers to a 3- to 12-membered monocyclic or polycyclic ring having one or more, preferably 1 to 4, the same or different heteroatoms selected from the group consisting of oxygen (O), nitrogen (N), and sulfur (S), but not including an aromatic ring. Non-limiting examples of heteroaryls or heterocycles include oxetane, pyrrolidine, pyrrole, tetrahydrofuran, furan, tetrahydrothiophene, thiophene, imidazolidine, imidazole, pyrazolidine, pyrazole, pyrrolidine, oxazolidine, oxazole, isoxazolidine, isoxazole, thiazolidine, thiazole, isothiazolidine, isothiazole, dioxolane, dithiolane, oxadiazole, thiadiazole, dithiazole, tetrazole, oxatetrazole, thiatetrazole, piperidine, pyridine, pyrimidine, tetrahydropyran, pyran, thiane, thiopyran, piperazine, diazine, morpholine, aryl ... Examples of suitable aryl groups include, but are not limited to, phosphorus, oxazine, dioxane, indole, indoline, benzodioxole, benzothiophene, benzofuran, benzimidazole, benzoxazole, benzisoxazole, benzothiazole, benzothiadiazole, benzotriazole, quinoline, isoquinoline, purine, furopyridine, mono- or di-azabicycles (e.g., quinuclidine, diazabicycloheptane, monoazabicyclooctane, diazaspirondecane, etc.), hexahydropyrrolopyrrole, pyrrolopyrrole, pyrrolopyridine, imidazopyridazine, dihydrobenzodioxine, dihydrobenzofuran, and the like.

[0022] The term "amino" means "-NH 2 The term "alkylamino" refers to an amino group substituted with mono- or di-alkyl. For example, C 1 ~C 6The alkylamino group may be mono- or di-C 1 ~C 6 Contains an amino group substituted with an alkyl group.

[0023] The term "alkylthio" refers to the group "-SR" where R is alkyl. The term "cyano" refers to "-CN".

[0024] The present invention relates to a derivative having a 6,6-fused bicyclic group, i.e., a 1,2,3,4-tetrahydronaphthalene group, or a pharma- ceutically acceptable salt thereof, i.e., a compound represented by the formula 1: [ka] (In the formula, L is -O-, -CO-, -CR 1 R 2 -, or -NR 3 - and R 1 and R 2 are each independently hydrogen; halogen; C 1 ~C 6 Alkyl; C with nitrogen, oxygen, or sulfur atoms 1 ~C 6 Alkyl;C 3 ~C 10 Cycloalkyl; 3-12 membered heterocyclic group; or C 1 ~C 6 is an alkoxy; R 3 is hydrogen; C 1 ~C 6 Alkyl; C with nitrogen, oxygen, or sulfur atoms 1 ~C 6 Alkyl;C 3 ~C 10 Cycloalkyl; 3-12 membered heterocyclic group; or C 1 ~C 6 is an alkoxy; X is hydrogen; halogen; C 1 ~C 6 Alkyl; C substituted with 1 to 3 halogens 1 ~C 6Alkyl; C with nitrogen, oxygen, or sulfur atoms 1 ~C 6 Alkyl;C 1 ~C 6 Alkoxy; or C substituted with 1 to 3 halogens 1 ~C 6 is an alkoxy; Y, Q and Z each independently represent -CR 4 R 5 - and R 4 and R 5 are each independently hydrogen; halogen; C 1 ~C 6 Alkyl; C with nitrogen, oxygen, or sulfur atoms 1 ~C 6 Alkyl;C 3 ~C 10 Cycloalkyl; 3-12 membered heterocyclic group; or C 1 ~C 6 Alkoxy or R 4 and R 5 together with the carbon atom of Y, Q or Z to which they are attached, 3 ~C 10 Forming a cycloalkyl, W is a bond, -CH 2 -, -O-, -NH-, -CH 2 CH 2 -, -CH=CH-, or -C≡C-; Ring A is a 6- to 12-membered aryl; a 5- to 12-membered heteroaryl; 3 ~C 10 cycloalkyl; or a 3- to 12-membered heterocyclic group; X 1 , X 2 , X 3 , and X 4 are each independently hydrogen; cyano; halogen; C 1 ~C 6 Alkyl; C substituted with 1 to 3 halogens 1 ~C 6 Alkyl;C 3 ~C 10 Cycloalkyl; 3-12 membered heterocyclic group; C 1~C 6 Alkoxy;C 1 ~C 6 Alkoxy-C 1 ~C 6 Alkoxy; C substituted with 1 to 3 halogens 1 ~C 6 Alkoxy;C 1 ~C 6 Alkylthio; Morpholinyl; Amino; Mono- or Di-C 1 ~C 6 Alkylamino;C 1 ~C 6 alkylcarbonyl; hydroxy; or nitro) or a pharma- ceutically acceptable salt thereof.

[0025] In the compound of formula 1 according to the present invention or a pharma- ceutically acceptable salt thereof, L may be --O--.

[0026] In the compound of formula 1 according to the present invention or a pharma- ceutically acceptable salt thereof, X is hydrogen, halogen, or C 1 ~C 6 It may be an alkoxy.

[0027] In the compound of formula 1 according to the present invention or a pharma- ceutically acceptable salt thereof, R 4 and R 5 are each independently hydrogen or C 1 ~C 6 alkyl or R 4 and R 5 together with the carbon atom of Y, Q or Z to which they are attached. 3 ~C 10 In one embodiment, Y is -CH 2 In another embodiment, Q is -CH 2 In yet another embodiment, Y is -CH 2 -Q may be -CH 2 - may be; Z is -CR 4 R 5 -May be;R4 and R 5 are each independently hydrogen or C 1 ~C 6 alkyl or R 4 and R 5 However, together with the carbon atom of Z, 3 ~C 10 It may form a cycloalkyl.

[0028] In the compound of formula 1 according to the present invention or a pharma- ceutically acceptable salt thereof, W may be a bond (ie, the A ring is directly bonded to the 1,2,3,4-tetrahydronaphthalene group).

[0029] In the compound of formula 1 according to the present invention or a pharma- ceutically acceptable salt thereof, the A ring may be phenyl, benzodioxolyl, 2,3-dihydrobenzodioxinyl, 2,3-dihydrobenzofuranyl, pyridinyl, pyrrolo[2.3-b]pyridinyl, pyrimidinyl, or thienyl.

[0030] In the compound of formula 1 according to the present invention or a pharma- ceutically acceptable salt thereof, X 1 , X 2 , X 3 , and X 4 are each independently hydrogen; cyano; halogen; C 1 ~C 6 Alkyl; C substituted with 1 to 3 halogens 1 ~C 6 Alkyl;C 3 ~C 10 Cycloalkyl;C 1 ~C 6 Alkoxy;C 1 ~C 6 Alkoxy-C 1 ~C 6 Alkoxy; C substituted with 1 to 3 halogens 1 ~C 6 Alkoxy; Morpholinyl; Mono- or Di-C 1 ~C 6 Alkylamino; or C 1 ~C 6It may be an alkylcarbonyl.

[0031] In a preferred embodiment of the present invention, L is -O-; X is hydrogen, halogen, or C 1 ~C 6 is an alkoxy; R 4 and R 5 are each independently hydrogen or C 1 ~C 6 alkyl or R 4 and R 5 together with the carbon atom of Y, Q or Z to which they are attached. 3 ~C 10 Forming a cycloalkyl, W is a bond; the A ring is phenyl, benzodioxolyl, 2,3-dihydrobenzodioxinyl, 2,3-dihydrobenzofuranyl, pyridinyl, pyrrolo[2.3-b]pyridinyl, pyrimidinyl, or thienyl; X 1 , X 2 , X 3 , and X 4 are each independently hydrogen; cyano; halogen; C 1 ~C 6 Alkyl; C substituted with 1 to 3 halogens 1 ~C 6 Alkyl;C 3 ~C 10 Cycloalkyl;C 1 ~C 6 Alkoxy;C 1 ~C 6 Alkoxy-C 1 ~C 6 Alkoxy; C substituted with 1 to 3 halogens 1 ~C 6 Alkoxy; Morpholinyl; Mono- or Di-C 1 ~C 6 Alkylamino; or C 1 ~C 6 It is an alkylcarbonyl.

[0032] In the above embodiment, Y is -CH 2 -- may be.

[0033] In the above embodiment, Q is -CH 2 -- may be.

[0034] In the above embodiment, Y is -CH 2 -Q may be -CH 2 - may be; Z is -CR 4 R 5 -May be;R 4 and R 5 are each independently hydrogen or C 1 ~C 6 alkyl or R 4 and R 5 C together with the Z carbon atom 3 ~C 10 It may form a cycloalkyl.

[0035] In the compound of formula 1 or a pharma- ceutically acceptable salt thereof, preferred compounds include those selected from the group consisting of: (S)-Quinuclidin-3-yl (6-(4-fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-(difluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(p-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,4-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,5-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,5-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,4-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,3-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,3,4-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,4,5-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,5-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,5-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-(2-methoxyethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-(methoxymethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-(2-methoxyethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-(methoxymethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-(2-methoxyethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-(methoxymethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-ethylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-propylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-butylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-isopropylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-isobutylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-(tert-butyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-cyclopropyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-ethylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-(tert-butyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-isopropylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-ethylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,3-dihydrobenzofuran-6-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-morpholinophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-fluoropyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-methylpyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-methoxypyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(1H-pyrrolo[2,3-b]pyridin-5-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(pyrimidin-5-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(4-fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(4-chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(p-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(3-(fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(3-(chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(2-(fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(2-chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(2-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(3,4-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(2,4-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(2,4,5-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(2,5-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(3,5-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(2,3,4-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(2,5-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(pyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(pyridin-3-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(o-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(2-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(2-ethoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(3-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(2-isopropoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(4-(2-methoxyethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(4-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(4-ethoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(4-propoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(4-isopropoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(benzo[d]dioxol-5-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(m-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(4-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(3-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(2-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(2-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(p-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-(difluoromethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,4-difluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,4-difluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,3-difluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,5-difluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,5-difluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,5-dichlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,4-dichlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,5-dichlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(2,4,5-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(2,3,4-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-methoxypyridin-4-yl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(2-methylpyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-fluoropyridin-4-yl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(2-(trifluoromethyl)pyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-ethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-chloro-4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-chloro-3-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-chloro-5-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-fluoro-4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-ethylphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-(tert-butyl)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-isopropylphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-(difluoromethyl)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-(dimethylamino)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,3-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,4-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,5-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,6-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,4-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,5-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-chloro-4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-chloro-4-ethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-chloro-4-propoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-fluoro-4-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-butoxy-3-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-ethoxy-3-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-fluoro-4-propoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,5-dimethyl-4-propoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-butoxy-3,5-dimethylphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-fluoro-4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-chloro-4-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-acetylthiophen-3-yl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(4-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(4-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-7-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-7-(4-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(3-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(3-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-7-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-7-(3-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(2-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(2-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-7-(2-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-7-(2-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-7-(2-(p-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(4-(difluoromethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(4-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(3-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(2-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(4-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(3-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(2-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7'-(4-fluorophenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (7'-(4-chlorophenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (7'-(4-(trifluoromethyl)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (7'-(4-(trifluoromethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (7'-(3-fluorophenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (7'-(3-chlorophenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (7'-(3-(trifluoromethyl)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (7'-(3-(trifluoromethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (7'-(2-fluorophenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (7'-(2-chlorophenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (7'-(2-(trifluoromethyl)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (7'-(2-(trifluoromethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (7'-(p-tolyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (7'-(4-(difluoromethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (7'-(4-(methoxymethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-fluorophenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-chlorophenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-(trifluoromethyl)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-(trifluoromethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3-fluorophenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3-chlorophenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3-(trifluoromethyl)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3-(trifluoromethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-(2-methoxyethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3-(2-methoxyethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(2-(2-methoxyethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-(methoxymethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3-(methoxymethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(2-(methoxymethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(2-chloro-4-methoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-chloro-3-methoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3-fluoro-4-methoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3-ethylphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3-(tert-butyl)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3-isopropylphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3-(difluoromethyl)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3-(dimethylamino)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3-isopropoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(2,3-dimethoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(2,4-dimethoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(2,5-dimethoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(2,6-dimethoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3,4-dimethoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3,5-dimethoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-methoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3-methoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-ethoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3-ethoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-isopropoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-propoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-ethylphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-propylphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-isopropylphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-isobutylphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-(tert-butyl)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-cyclopropylphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (7-fluoro-6-(3-fluoro-4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,5-dimethyl-4-propoxyphenyl)-(7-fluoro-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-fluoro-2,2-dimethyl-6-(4-propylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-fluoro-6-(4-isobutylphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-(tert-butoxy)pyridin-4-yl)-(7-fluoro-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-fluoro-6-(4-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-fluoro-4-methoxyphenyl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,5-dimethyl-4-propoxyphenyl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-methoxy-2,2-dimethyl-6-(4-propylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-isobutylphenyl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-(tert-butoxy)pyridin-4-yl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; and (S)-Quinuclidin-3-yl (6-(4-isopropoxyphenyl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate.

[0036] The compound of formula 1 or a pharma- ceutically acceptable salt thereof may be in the form of a cis- or trans-geometric isomer. Unless otherwise specified, the compound of formula 1 or a pharma- ceutically acceptable salt thereof includes both cis- and trans-geometric isomers. In addition, the compound of formula 1 or a pharma- ceutically acceptable salt thereof may have a substituent that includes an asymmetric atom. Thus, it may be in the form of a racemic mixture (RS) or in the form of an optical isomer, such as an (R)- or (S)-isomer. The compound of formula 1 or a pharma- ceutically acceptable salt thereof includes both a racemic mixture (RS) and each optical isomer, such as an (R)- or (S)-isomer, unless otherwise specified. In addition, the compound of formula 1 or a pharma- ceutically acceptable salt thereof may have two or more chiral centers. Thus, it may be in the form of one or more diastereomers or a mixture thereof. The compound of formula 1 or a pharma- ceutically acceptable salt thereof includes both each diastereomer and a mixture thereof, unless otherwise specified.

[0037] The compound of formula 1 of the present invention can be in the form of a pharma- ceutically acceptable salt.The salt may be in the form of a conventional acid addition salt, including salts derived from inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, perchloric acid, or hydrobromic acid; and salts derived from organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, succinic acid, benzoic acid, citric acid, maleic acid, malonic acid, malic acid, tartaric acid, gluconic acid, lactic acid, gentisic acid, fumaric acid, lactobionic acid, salicylic acid, phthalic acid, embonic acid, aspartic acid, glutamic acid, or acetylsalicylic acid.The salt also includes salts derived from amino acids such as glycine, alanine, valine, isoleucine, serine, cysteine, cystine, aspartic acid, glutamine, lysine, arginine, tyrosine, or proline. Additionally, the salts include those derived from sulfonic acids, such as, for example, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, or toluenesulfonic acid.

[0038] The compound of formula 1 according to the present invention or a pharma- ceutically acceptable salt thereof can be prepared according to various methods.

[0039] For example, as shown in the following reaction scheme 1, the compound of formula 1a or a pharma- ceutically acceptable salt thereof according to the present invention can be prepared by reacting a compound of formula 2 or a salt thereof with ethyl chloroformate to obtain a compound of formula 3; coupling the compound of formula 3 with a compound of formula 4 to obtain a compound of formula 5; and reacting the compound of formula 5 with X 1 , X 2 , X 3 , or X 4 with an AW-boronic acid substituted with , to obtain a compound of formula 1a; and optionally converting said compound of formula 1a into a pharma- ceutically acceptable salt thereof. [ka]

[0040] In the reaction formula 1, X, Y, Q, Z, W, A ring, X 1 , X 2 , X 3 , and X 4 is the same as defined above.

[0041] The compound of formula 2 is commercially available or a known compound, or may be synthesized according to the literature. The reaction of the compound of formula 2 or a salt thereof with ethyl chloroformate may be carried out in the presence of an organic base such as triethylamine, N,N-diisopropylethylamine, or an inorganic base such as potassium carbonate. The base may be used in an amount ranging from 1 to 1.5 equivalents relative to 1 equivalent of the compound of formula 2, or in an amount ranging from 3 to 5 equivalents relative to 1 equivalent of the salt of the compound of formula 2 (e.g., hydrochloride). The reaction may be carried out in a solvent such as dichloromethane or tetrahydrofuran, preferably at 0° C. to room temperature.

[0042] The coupling of the compound of formula 3 with the compound of formula 4 (i.e., quinuclidinol) may be carried out by a condensation reaction involving the removal of ethanol. The reaction may be preferably carried out in the presence of a base such as sodium hydride. The reaction may also be carried out in a non-polar organic solvent such as toluene at 120°C to 140°C.

[0043] Compound of formula 5 and X 1 , X 2 , X 3 , or X 4 The reaction with AW-boronic acids substituted with tetrakis(triphenylphosphine)palladium(0) (Pd(PPh 3 ) 4 ), palladium(II) acetate (Pd(OAc) 2 ), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (Pd(dppf)Cl 2 The Suzuki reaction may also be carried out using a palladium catalyst such as cesium carbonate (Cs 2 CO 3 ), Sodium Carbonate (Na 2 CO 3 ), potassium carbonate (K 2 CO 3 ), potassium phosphate (K 3 PO 4 The Suzuki reaction may be carried out in the presence of an inorganic base such as toluene, or in a polar organic solvent such as 1,4-dioxane, tetrahydrofuran, acetonitrile, 1,2-dimethoxyethane, or N,N-dimethylformamide at 50° C. to 150° C., preferably 80° C. to 120° C. Other reaction conditions including reaction time may be determined by known methods for the Suzuki reaction.

[0044] The conversion of the compound of formula 1a into its pharma- ceutically acceptable salt may be carried out according to conventional methods.For example, the pharma- ceutically acceptable salt of the compound of formula 1a may be prepared by dissolving the compound of formula 1a in a water-miscible solvent such as methanol, ethanol, acetone or 1,4-dioxane, followed by crystallization with the addition of a free acid or free base.

[0045] In addition, the compound of formula 1a or a pharma- ceutically acceptable salt thereof according to the present invention can be prepared by the steps of: reacting a compound of formula 4 with bis(4-nitrophenyl) carbonate to obtain a compound of formula 7; reacting the compound of formula 7 with a compound of formula 2 to obtain a compound of formula 5; and reacting the compound of formula 5 with X 1 , X 2 , X 3 , or X 4 with an AW-boronic acid substituted with , to obtain a compound of formula 1a; and optionally converting said compound of formula 1a into a pharma- ceutically acceptable salt thereof. [ka]

[0046] In the reaction formula 2, X, Y, Q, Z, W, A ring, X 1 , X 2 , X 3 , and X 4 is the same as defined above.

[0047] The reaction of the compound of formula 4 (i.e., quinuclidinol) with bis(4-nitrophenyl)carbonate may be carried out in a polar solvent such as N,N-dimethylformamide, preferably at 0° C. to 25° C. The compound of formula 7 may also be prepared by reacting the compound of formula 4 with 4-nitrophenyl chloroformate in a solvent such as dichloromethane, acetonitrile, or the like, in the presence of a base such as triethylamine.

[0048] The reaction of a compound of formula 7 with a compound of formula 2 may be carried out in a solvent such as N,N-dimethylformamide, tetrahydrofuran or acetonitrile in the presence of a base such as N,N-diisopropylethylamine or triethylamine at 0° C. to 25° C.

[0049] Compound of formula 5 and X 1 , X 2 , X 3 , or X 4 The reaction with AW-boronic acids substituted with may be carried out according to the Suzuki reaction, as described above, and the conversion of compounds of formula 1a to their pharma- ceutically acceptable salts may be carried out according to conventional methods, as described above.

[0050] The compound having a 1,2,3,4-tetrahydronaphthalene group according to the present invention, i.e., the compound of formula 1 or a pharma- ceutical acceptable salt thereof, has excellent inhibitory activity against glucosylceramide synthase (GCS). Therefore, the compound of formula 1 or a pharma-ceutical acceptable salt thereof can be usefully applied to the prevention or treatment of various diseases associated with GCS.

[0051] Thus, the present invention includes within its scope a pharmaceutical composition for inhibiting glucosylceramide synthase (GCS), comprising as an active ingredient a therapeutically effective amount of a compound of formula 1, or a pharma- ceutically acceptable salt thereof. In one embodiment, the present invention provides a pharmaceutical composition for preventing or treating diseases associated with GCS, such as Gaucher's disease, Fabry's disease, Tay-Sachs' disease, Parkinson's disease, etc., comprising as an active ingredient a therapeutically effective amount of a compound of formula 1, or a pharma- ceutically acceptable salt thereof.

[0052] The pharmaceutical composition of the present invention may include a pharma- ceutically acceptable carrier, such as a diluent, disintegrant, sweetener, lubricant, or flavoring agent.The pharmaceutical composition may be formulated into an oral preparation, such as a tablet, capsule, powder, granule, suspension, emulsion, or syrup; or into a parenteral preparation, such as an external solution, an external suspension, an external emulsion, a gel (e.g., ointment), an inhalant, a spray, or an injection.These preparations may be in various forms, for example, a single-dose dosage form or a multiple-dose dosage form.

[0053] The pharmaceutical composition of the present invention may contain, for example, a diluent (e.g., lactose, corn starch, etc.); a lubricant (e.g., magnesium stearate, etc.); an emulsifier; a suspending agent; a stabilizer; and / or an isotonic agent, etc. If necessary, the composition further contains a sweetener and / or a flavoring agent.

[0054] The compositions of the present invention may be administered orally or parenterally, including routes of administration such as inhalation, intravenous, intraperitoneal, subcutaneous, rectal and topical. Thus, the compositions of the present invention may be formulated in various forms, such as tablets, capsules, aqueous solutions or suspensions. For tablets for oral administration, carriers such as lactose, corn starch and lubricants such as magnesium stearate are usually used. For capsules for oral administration, lactose and / or dried corn starch can be used as diluents. When an aqueous suspension for oral administration is required, the active ingredient can be combined with emulsifying and / or suspending agents. If necessary, certain sweetening and / or flavoring agents can be used. For intramuscular, intraperitoneal, subcutaneous and intravenous administration, a sterile solution of the active ingredient is usually prepared, and the pH of the solution must be appropriately adjusted and buffered. For intravenous administration, the total concentration of solutes must be adjusted to make the formulation isotonic. The compositions of the present invention may be in the form of an aqueous solution containing a pharma-ceutically acceptable carrier, such as saline having a pH value of 7.4. The solution may be introduced into a patient's intramuscular blood stream by local bolus injection.

[0055] The compound of formula 1 or a pharma- ceutically acceptable salt thereof can be administered to a subject in a therapeutically effective amount ranging from about 0.0001 mg / kg to about 100 mg / kg per day. Of course, the dosage can be varied depending on the age, weight, sensitivity, symptoms, or activity of the compound of the subject.

[0056] The present invention includes within its scope a method for inhibiting glucosylceramide synthase (GCS) in a mammal, comprising administering to a mammal in need thereof a therapeutically effective amount of a compound of formula 1, or a pharma- ceutically acceptable salt thereof. In one embodiment, the present invention provides a method for treating a disease associated with GCS, such as Gaucher disease, Fabry disease, Tay-Sachs disease, Parkinson's disease, etc., comprising administering to a mammal in need thereof a therapeutically effective amount of a compound of formula 1, or a pharma- ceutically acceptable salt thereof.

[0057] The present invention also provides the use of a compound of formula 1, or a pharma- ceutically acceptable salt thereof, for the manufacture of a medicament for inhibiting glucosylceramide synthase (GCS) in a mammal. In one embodiment, the present invention provides the use of a compound of formula 1, or a pharma- ceutically acceptable salt thereof, for the manufacture of a medicament for preventing or treating a disease associated with GCS, such as Gaucher disease, Fabry disease, Tay-Sachs disease, Parkinson's disease, etc. EXAMPLES

[0058] The following examples and test examples are intended to illustrate the present invention and are not intended to limit the scope of the present invention.

[0059] In the following examples, brine means saturated aqueous sodium chloride solution. All temperatures are in degrees Celsius (° C.) unless otherwise noted. All reactions were performed at room temperature unless otherwise noted.

[0060] The compounds prepared in the following Preparations and Examples were analyzed as follows: Nuclear Magnetic Resonance (NMR) spectroscopy was performed using a Bruker 400 MHz spectrometer and chemical shifts (unit: ppm) were analyzed. Column chromatography was performed using silica gel (Merck, 70-230 mesh). Each starting material was a known compound, which was either synthesized according to the literature or purchased commercially. All reactions and chromatographic fractions were analyzed by thin layer chromatography (TLC) on 250 nm silica gel plates and were chromatographed using ultraviolet or iodine (I 2 ) staining and visualized.

[0061] Production Example 1: (S)-Quinuclidin-3-yl (6-bromo-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate Step 1: Ethyl (6-bromo-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 6-Bromo-1,2,3,4-tetrahydronaphthalen-1-amine (20 g, 82.6 mmol) was dissolved in dichloromethane (250 mL), and then triethylamine (12.7 ml, 90.9 mmol) and ethyl chloroformate (8.7 ml, 90.9 mmol) were slowly added. The reaction mixture was stirred at room temperature for 4 hours. Water was added to the reaction mixture, and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (n-hexane / ethyl acetate = 1 / 1, v / v) to obtain the title compound as a white solid. (20.7 g, yield: 83%) 1 H-NMR (400MHz, CDCl 3 ) δ 7.31~7.21(m, 3H), 4.85(s, 1H), 4.18(m, 2H), 2.76(m, 2H), 2.06(m, 1H), 1.83(m, 3H), 1.28(t, 3H)

[0062] Step 2: (S)-Quinuclidin-3-yl (6-bromo-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate (S)-(+)-3-Quinuclidinol (25.6 g, 201.2 mmol) was dissolved in toluene (200 ml), and sodium hydride (1.6 g, 67.1 mmol) was added at 0° C. The reaction mixture was stirred for 15 minutes, and then ethyl (6-bromo-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate (20 g, 67.1 mmol) prepared in step 1 was added. The reaction mixture was refluxed and stirred at 140° C. for 21 hours, and then cooled to room temperature. Brine was added to the reaction mixture, and then extracted with ethyl acetate. The organic layer was washed twice with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by column chromatography (ethyl acetate / (methanol / aqueous ammonia=1 / 1)=9 / 1, v / v) to obtain the title compound as a white solid. (17 g, yield: 66%) 1 H-NMR (400MHz, CDCl 3 ) δ 7.31~7.19(m, 3H), 5.08(m, 1H), 4.85(m, 1H), 4.77(br, 1H), 3.24(m, 1H), 2.84(m, 2H) , 2.74(m, 4H), 2.10~2.05(m, 3H), 1.83(m, 4H), 1.69(m, 1H), 1.58(m, 1H), 1.38(m, 1H)

[0063] Production Example 2: (S)-Quinuclidin-3-yl (7-bromo-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate The title compound was prepared following a procedure similar to Preparation 1 using 7-bromo-1,2,3,4-tetrahydronaphthalen-1-amine as the starting material. 1 H-NMR (400MHz, CDCl 3 ) δ 7.39(d, 1H), 7.28(d, 1H), 7.02(d, 1H), 4.76(s, 2H), 3.26(q, 1H), 2.87~2.71 (m, 7H), 2.11~1.88 (m, 4H), 1.85~1.72 (m, 3H), 1.70~1.61 (bs, 1H), 1.56~1.46 (m, 1H)

[0064] Production Example 3: (S)-Quinuclidin-3-yl (6-bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate Step 1: 6-Bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1(2H)-one 6-Bromo-1,2,3,4-tetrahydronaphthalen-1-one (20 g, 88.9 mmol) was dissolved in tetrahydrofuran (70 ml), and then 60% sodium hydride (17.8 g, 444.3 mmol) was added at 0°C. The reaction mixture was stirred for 15 minutes, and then iodomethane (22.1 ml, 355.4 mmol) was added slowly at the same temperature. The reaction mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and then it was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The obtained residue was purified by column chromatography (n-hexane / ethyl acetate = 10 / 1, v / v) to obtain the title compound as a white solid. (20 g, yield: 90%) 1 H-NMR (400MHz, CDCl 3 ) δ 8.03(d, 1H), 7.74(d, 1H), 7.21(t, 1H), 3.00(m, 2H), 2.01(m, 2H), 1.22(s, 6H)

[0065] Step 2: 6-Bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-amine hydrochloride 6-Bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1(2H)-one (20 g, 79.0 mmol) prepared in step 1 was dissolved in methanol (300 ml), and then ammonium acetate (121.8 g, 1580.1 mmol) and sodium cyanoborohydride (24.8 g, 395.0 mmol) were added. The reaction mixture was stirred at room temperature for 4 hours, and then refluxed at 80° C. for 12 hours. The reaction mixture was cooled to room temperature, basified with 1N sodium hydroxide solution to pH>12, and then extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. Ethyl acetate was added to the resulting residue, followed by the addition of a solution of hydrochloric acid (4M) in 1,4-dioxane. The mixture was stirred at room temperature for 1 hour. The resulting solid was filtered under reduced pressure, washed with ethyl acetate, and then dried to obtain the title compound as a white solid. (12 g, yield: 52%) 1 H-NMR (400MHz, CD 3 OD) δ 7.68(d, 1H), 7.41(d, 1H), 7.25(t, 1H), 4.13(s, 1H), 2.96(m, 1H), 2.75(m, 1H), 1.88(m, 1H), 1.75(m, 1H), 1.20(s, 3H), 1.03(s, 3H)

[0066] Step 3: (S)-Quinuclidin-3-yl (6-bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate A solution of (S)-(+)-3-quinuclidinol (6.3 g, 49.5 mmo) and bis(4-nitrophenyl)carbonate (15.1 g, 49.5 mmol) in N,N-dimethylformamide (80 mL) was stirred at room temperature for 8 hours. 6-Bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-amine hydrochloride (20 g, 41.3 mmol) prepared in step 2 and diisopropylethylamine (21.6 mL, 123.9 mmol) were added to the solution, which was then stirred at room temperature overnight. The reaction mixture was extracted with diisopropyl ether (100 ml x 2). The aqueous layer was basified to pH 12 with ammonia, and then extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (ethyl acetate / (methanol / aqueous ammonia=1 / 1)=9 / 1, v / v) to give the title compound as a white solid (6 g, yield: 36%). 1 H-NMR (400MHz, CDCl 3 ) δ 7.25(m, 2H), 7.12(m, 1H), 5.09(m, 1H), 4.95(m, 1H), 4.53(m, 1H), 3.20(m, 1H), 2.84~2.65(m, 7H) ), 1.95(m, 1H), 1.81(m, 2H), 1.66(br, 1H), 1.53(br, 1H), 1.38(br, 1H), 0.99(m, 3H), 0.88(m, 3H)

[0067] Production Example 4: (S)-Quinuclidin-3-yl (7-bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate Step 1: 7-Bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1(2H)-one The title compound was prepared according to a procedure similar to that of Step 1 of Preparation 3 using 7-bromo-3,4-dihydronaphthalen-1(2H)-one as the starting material. 1 H-NMR (400MHz, CDCl 3) δ 8.16(s, 1H), 7.57(d, 1H), 7.12(d, 1H), 2.94(m, 2H), 1.99(m, 2H), 1.27(s, 6H)

[0068] Step 2: (7-Bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-amine hydrochloride The title compound was prepared according to the same procedure as in Step 2 of Preparation 3 using 7-bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1(2H)-one prepared in Step 1. 1 H-NMR (400MHz, MeOD) δ 7.60(s, 1H), 7.51(d, 1H), 7.20(d, 1H), 4.09(s, 1H), 3.88(m, 2H), 1.87(m, 1H), 1.70(m, 1H), 1.16(s, 3H), 1.05(s, 3H)

[0069] Step 3: Ethyl (7-bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate The title compound was prepared according to the same procedure as in Step 1 of Preparation 1 using 7-bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-amine hydrochloride prepared in Step 2.

[0070] Step 4: (S)-Quinuclidin-3-yl (7-bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate The title compound was prepared according to the same procedure as in Step 2 of Preparation 1 using ethyl (7-bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate prepared in Step 3. 1 H-NMR (400MHz, CDCl 3) δ 7.40(m, 1H), 7.25(m, 1H), 6.95(d, 1H), 5.09(m, 1H), 4.78(m, 1H), 4.59(m, 1H), 3.22(m, 1H), 2.86~2. 68(m, 7H), 1.98(m, 1H), 1.82(m, 2H), 1.66(m, 1H), 1.55(m, 1H), 1.38(m, 1H), 1.00(m, 3H), 0.88(m, 3H)

[0071] Production Example 5: (S)-Quinuclidin-3-yl (6'-bromo-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate Step 1: (2-Chloroethyl)dimethylsulfonium iodide A solution of 2-chloroethyl methyl sulfide (10 g, 90.4 mmol) in iodomethane (50 ml) was stirred at room temperature for 2 days. The resulting solid was filtered under reduced pressure, washed with acetone, and then dried to give the title compound. (16 g, yield: 70%) The product was used in the next reaction without further purification.

[0072] Step 2: 6'-Bromo-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-one 6-Bromo-3,4-hydronaphthalen-1(2H)-one (1.03 g, 4.58 mmol) was dissolved in tert-butanol (10 mL), and then sodium iodide (0.131 g, 0.872 mmol) and 60% sodium hydride (0.349 g, 8.72 mmol) were added slowly. The reaction mixture was stirred at room temperature for 20 minutes. (2-Chloroethyl)dimethylsulfonium iodide (1.10 g, 4.36 mmol) prepared in step 1 was added slowly to the reaction mixture over 1 hour, and then the mixture was stirred at room temperature overnight. The reaction was quenched by adding water (15 ml) to the reaction mixture, and then extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (n-hexane / ethyl acetate = 10 / 1, v / v) to obtain the title compound as a white solid. (789 mg, yield: 78%) 1 H-NMR (400MHz, CDCl 3 ) δ 7.99(d, 1H), 7.73(d, 1H), 7.19(t, 1H), 3.08(m, 2H), 1.99(m, 2H), 1.40(d, 2H), 0.86(d, 2H)

[0073] Step 3: 6'-Bromo-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalene]-1'-amine hydrochloride The title compound was prepared according to the same procedure as in Step 2 of Preparation 3 using 6'-bromo-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-one prepared in Step 2. 1 H-NMR (400MHz, MeOD) δ 7.67(d, 1H), 7.37(d, 1H), 7.23(t, 1H), 3.68(s, 1H), 3.09(m, 1H), 2.82(m, 1H) , 2.39(m, 1H), 1.26(m, 1H), 0.93(m, 1H), 0.79(m, 1H), 0.69(m, 1H), 0.55(m, 1H)

[0074] Step 4: Ethyl (6'-bromo-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate The title compound was prepared using 6'-bromo-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalene]-1'-amine hydrochloride prepared in Step 3, following the same procedure as in Step 1 of Preparation 1. The product was used in the next reaction without further purification. 1 H-NMR (400MHz, CDCl 3 ) δ 7.48(d, 1H), 7.30(m, 1H), 7.06(t, 1H), 4.98(br, 1H), 4.27(d, 1H), 4.15(m, 2H), 2.95(m, 1H) , 2.74(m, 1H), 2.03(m, 1H), 1.31(m, 1H), 1.27(m, 3H), 0.85(m, 1H), 0.50(m, 1H), 0.45(s, 2H)

[0075] Step 5: (S)-Quinuclidin-3-yl (6'-bromo-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate The title compound was prepared according to the same procedure as in Step 2 of Preparation 1 using ethyl (6'-bromo-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate prepared in Step 4. 1 H-NMR (400MHz, CDCl 3 ) δ 7.47(d, 2H), 7.27(m, 1H), 7.04(m, 1H), 5.30(m, 1H), 4.78~4.76(m, 2H), 4.23(d, 1H), 3.23(m, 1H), 2.86~2.67(m, 7) H), 2.42(br, 1H), 1.98(m, 1H), 1.83(m, 1H), 1.67(m, 1H), 1.55(m, 1H), 1.37(m, 1H), 0.85(m, 1H), 0.47~0.44(m, 2H)

[0076] Production Example 6: (S)-Quinuclidin-3-yl (7'-bromo-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate The title compound was prepared following a procedure similar to Preparation 5 using 7-bromo-3,4-hydronaphthalen-1(2H)-one as the starting material. 1 H-NMR (400MHz, CDCl 3 ) δ 7.41(s, 1H), 7.30(m, 1H), 6.99(d, 1H), 5.42(br, 1H), 4.77(m, 2H), 4.26(m, 1H), 3.22(m, 1H), 2.85~2.67(m, 7H), 2.10 (br, 1H), 1.98(m, 1H), 1.83(br, 1H), 1.67(br, 1H), 1.55(br, 1H), 1.39(br, 1H), 0.85(m, 1H), 0.51(m, 1H), 0.49(m, 2H)

[0077] Production Example 7: (S)-Quinuclidin-3-yl (6-bromo-7-fluoro-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate The title compound was prepared following a procedure similar to Preparation 3 using 6-bromo-7-fluoro-3,4-hydronaphthalen-1(2H)-one as the starting material. 1 H-NMR (400MHz, CDCl 3 ) δ 7.29(m, 2H), 7.04(m, 1H), 4.78(m, 2H), 4.56(d, 1H), 3.25(m, 1H), 2.93~2.74(m, 7H), 2.09( br, 1H), 1.82(br, 1H), 1.71(br, 3H), 1.59(br, 1H), 1.42(br, 1H), 1.03(d, 3H), 0.91(d, 3H)

[0078] Production Example 8: (S)-Quinuclidin-3-yl (6-bromo-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate The title compound was prepared following a procedure similar to Preparation 3 using 6-bromo-7-methoxy-3,4-hydronaphthalen-1(2H)-one as the starting material. 1 H-NMR (400MHz, CDCl 3 ) δ 7.27(m, 2H), 6.79(m, 1H), 4.77(m, 2H), 4.55(d, 1H), 3.84(d, 3H), 3.25(m, 1H), 2.93~2.74(m, 7H) , 2.09(br, 1H), 1.89(br, 1H), 1.71(br, 3H), 1.56(br, 1H), 1.41(br, 1H), 1.03(d, 3H), 0.95(d, 3H)

[0079] Example 1: (S)-Quinuclidin-3-yl (6-(4-fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1,4-Dioxane (1 ml) and water (0.5 ml) were gradually added to a mixture of (S)-quinuclidin-3-yl-(6-bromo-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate (30 mg, 0.079 mmol) prepared in Preparation Example 1, 4-fluorophenylboronic acid (16.6 mg, 0.12 mmol), potassium phosphate (50.4 mg, 0.23 mmol), and tetrakis(triphenylphosphine)palladium(0) (9.1 mg, 10 mol%). The reaction mixture was refluxed and stirred at 120° C. overnight, and then cooled to room temperature. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting yellow oily residue was purified by silica gel column chromatography (ethyl acetate / (methanol / aqueous ammonia=1 / 1)=9 / 1, v / v) to obtain the title compound as a white solid. (20 mg, yield: 65%) 1 H-NMR (400MHz, CDCl 3 ) δ 7.53(m, 2H), 7.39(m, 2H), 7.26(m, 1H), 7.13(m, 2H), 5.02(m, 2H), 4.80(m, 1H), 3.27(m, 1H) ), 2.87~2.77(m, 7H), 2.08(m, 2H), 1.89(m, 4H), 1.71(br, 1H), 1.60(br, 1H), 1.40(br, 1H)

[0080] Examples 2 to 54 The title compounds of Examples 2 to 54 were prepared according to the same procedure as in Example 1 using (S)-quinuclidin-3-yl (6-bromo-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate prepared in Preparation Example 1 and the corresponding substituted boronic acids, respectively.

[0081] Example 2: (S)-Quinuclidin-3-yl (6-(4-chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.51(m, 2H), 7.42(m, 3H), 7.29(m, 2H), 5.00(m, 2H), 4.81(br, 1H), 3.30(m, 1H), 2.8 7~2.77(m, 7H), 2.06(m, 2H), 1.89(m, 4H), 1.71(br, 1H), 1.60(br, 1H), 1.41(br, 1H)

[0082] Example 3: (S)-Quinuclidin-3-yl (6-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.69(s, 3H), 7.45(m, 2H), 7.35(m, 1H), 7.28(d, 1H), 4.99(m, 2H), 4.80(br, 1H), 3.29(m, 1 H), 2.88~2.77(m, 7H), 2.14(m, 2H), 1.91(m, 4H), 1.71(br, 1H), 1.61(br, 1H), 1.41(br, 1H)

[0083] Example 4: (S)-Quinuclidin-3-yl (6-(4-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.57(d, 1H), 7.42(m, 4H), 7.28(m, 2H), 5.00(m, 2H), 4.80(br, 1H), 3.28(m, 1H), 2.8 6~2.77(m, 7H), 2.08(m, 2H), 1.90(m, 4H), 1.71(br, 1H), 1.60(br, 1H), 1.40(br, 1H)

[0084] Example 5: (S)-Quinuclidin-3-yl (6-(3-fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.46~7.36(m, 4H), 7.30~7.28(m, 2H), 7.04(t, 1H), 5.00(m, 2H), 4.80(m, 1H), 3.28(m, 1H) ), 2.88~2.77(m, 7H), 2.13(m, 2H), 1.89(m, 4H), 1.71(br, 1H), 1.60(br, 1H), 1.40(br, 1H)

[0085] Example 6: (S)-Quinuclidin-3-yl (6-(3-chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.56(s, 1H), 7.44(m, 1H), 7.37(m, 2H), 7.23(m, 2H), 5.00(m, 2H), 4.80(br, 1H), 3.28(m, 1H) , 2.88~2.77(m, 7H), 2.09(m, 2H), 1.90~1.82(m, 4H), 1.71(br, 1H), 1.60(m, 1H), 1.41(m, 1H)

[0086] Example 7: (S)-Quinuclidin-3-yl (6-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.81(s, 1H), 7.76(d, 1H), 7.62~7.54(m, 2H), 7.44(m, 2H), 7.34(s, 1H), 5.06~5.03(m, 2H), 4.81(br, 1H), 3.28 (m, 1H), 2.88~2.74(m, 7H), 2.12(m, 2H), 1.90(m, 3H), 1.83(br, 1H), 1.71(br, 1H), 1.60(br, 1H), 1.41(br, 1H)

[0087] Example 8: (S)-Quinuclidin-3-yl (6-(3-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl3 ) δ 7.50~7.41(m, 5H), 7.31(s, 1H), 7.22(m, 1H), 5.06~5.04(m, 2H), 4.80(br, 1H), 3.27(m, 1H), 2.87 ~2.77(m, 7H), 2.08(m, 2H), 1.90(m, 3H), 1.82(br, 1H), 1.70(br, 1H), 1.60(br, 1H), 1.40(br, 1H)

[0088] Example 9: (S)-Quinuclidin-3-yl (6-(2-fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.44(m, 3H), 7.34(m, 2H), 7.23(m, 1H), 7.18(m, 1H), 5.03(m, 1H), 4.97(br, 1H), 4.80(br, 1H), 3. 28(m, 1H), 2.86~2.77(m, 7H), 2.06(m, 2H), 1.90(m, 4H), 1.70(br, 1H), 1.60(br, 1H), 1.40(br, 1H)

[0089] Example 10: (S)-Quinuclidin-3-yl (6-(2-chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.71(m, 1H), 7.66(m, 1H), 7.44(m, 4H), 7.18(s, 1H), 5.08(m, 1H), 4.98(br, 1H), 4.81(br, 1H), 3. 28(m, 1H), 2.90~2.78(m, 7H), 2.13(m, 1H), 1.90(m, 5H), 1.70(br, 1H), 1.60(br, 1H), 1.40(br, 1H)

[0090] Example 11: (S)-Quinuclidin-3-yl (6-(2-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl3 ) δ 7.74(m, 1H), 7.56(m, 1H), 7.55(, 1H), 7.47(br, 1H), 7.32(m, 1H), 7.16(br, 1H), 7.07(s, 1H), 5.07(m, 1H), 4.96(m, 1) H), 4.80(m, 1H), 3.29(m, 1H), 2.88~2.81(m, 7H), 2.09(m, 2H), 1.90(m, 4H), 1.71(br, 1H), 1.61(br, 1H), 1.41(br, 1H)

[0091] Example 12: (S)-Quinuclidin-3-yl (6-(2-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.41~7.37(m, 4H), 7.31(m, 2H), 7.20(s 1H), 5.08(m, 1H), 4.97(br, 1H), 4.81(m, 1H), 3.30(m, 1H), 2.86~2.78(m, 7H), 2.14(m, 2H), 1.90(m, 4H), 1.70(br, 1H), 1.60(br, 1H), 1.40(br, 1H)

[0092] Example 13: (S)-Quinuclidin-3-yl (6-(4-(difluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.55(d, 2H), 7.40(m, 2H), 7.29(s, 1H), 7.18(d, 2H), 6.74~6.37(t, 1H), 5.18(m, 1H), 4.95(m, 1H), 4.79(m, 1H), 3 .27(m, 1H), 2.86~2.72(m, 7H), 2.08(m, 2H), 1.88(m, 3H), 1.82(br, 1H), 1.69(br, 1H), 1.59(br, 1H), 1.40(br, 1H)

[0093] Example 14: (S)-Quinuclidin-3-yl (6-(p-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.49(d, 2H), 7.42(d, 2H), 7.32(s, 1H), 7.27(m, 3H), 4.99(m, 2H), 4.79(br, 1H), 3.30(m, 1H), 2.87~2.78 (m, 7H), 2.41(s, 3H), 2.08(m, 2H), 1.89(m, 3H), 1.82(br, 1H), 1.70(br, 1H), 1.59(br, 1H), 1.41(br, 1H)

[0094] Example 15: (S)-Quinuclidin-3-yl (6-(3,4-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.43(m, 1H), 7.37(m, 2H), 7.26(m, 2H), 7.21(m, 1H), 4.98(m, 1H), 4.96(m, 1H), 4.80(br, 1H), 3.30(m, 1) H), 2.87~2.78(m, 7H), 2.09(m, 2H), 1.89(m, 3H), 1.81(m, 2H), 1.71(br, 1H), 1.61(br, 1H), 1.41(br, 1H)

[0095] Example 16: (S)-Quinuclidin-3-yl (6-(2,5-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.45(m, 1H), 7.37(m, 1H), 7.12(m, 2H), 7.00(m, 1H), 5.02(m, 2H), 4.81(m, 1H), 3.31(m, 1H) ), 2.87~2.78(m, 7H), 2.06(m, 2H), 1.89(m, 4H), 1.71(br, 1H), 1.60(br, 1H), 1.41(br, 1H)

[0096] Example 17: (S)-Quinuclidin-3-yl (6-(3,5-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.45(m, 1H), 7.39(m, 1H), 7.29(m, 1H), 7.10(d, 2H), 6.79(m, 1H), 5.00(m, 1H), 4.96(m, 1H), 4.81(br, 1 H), 3.30(m, 1H), 2.87~2.77(m, 7H), 2.13(m, 2H), 1.89(m, 4H), 1.71(br, 1H), 1.61(br, 1H), 1.41(br, 1H)

[0097] Example 18: (S)-Quinuclidin-3-yl (6-(2,4-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.43(m, 2H), 7.32(m, 1H), 7.24(s, 1H), 6.94(m, 2H), 5.00(m, 1H), 4.96(br, 1H), 4.79(br, 1H), 3.30( m, 1H), 2.86~2.77(m, 7H), 2.14(m, 2H), 1.89~1.83(m, 4H), 1.70(br, 1H), 1.60(br, 1H), 1.41(br, 1H)

[0098] Example 19: (S)-Quinuclidin-3-yl (6-(2,3-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.45(t, 1H), 7.37(br, 1H), 7.28(m, 1H), 7.15(m, 3H), 5.01(m, 1H), 4.97(m, 1H), 4.81(br, 1H), 3.30(m, 1 H), 2.86~2.75(br, 7H), 2.13(m, 2H), 1.90(m, 2H), 1.82(m, 2H), 1.71(br, 1H), 1.59(br, 1H), 1.40(br, 1H)

[0099] Example 20: (S)-Quinuclidin-3-yl (6-(2,3,4-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.45(t, 1H), 7.32(m, 1H), 7.24(s, 1H), 7.14(m, 1H), 7.05(m, 1H), 5.01(m, 2H), 4.80(br, 1H), 3.30(m, 1 H), 2.87~2.78(m, 7H), 2.14(m, 2H), 1.90(m, 2H), 1.80(m, 2H), 1.71(br, 1H), 1.60(br, 1H), 1.41(br, 1H)

[0100] Example 21: (S)-Quinuclidin-3-yl (6-(2,4,5-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.46(m, 1H), 7.31(m, 1H), 7.25(m, 2H), 7.02(t, 1H), 5.00(m, 2H), 4.80(br, 1H), 3.28(m, 1H), 2.8 6~2.73(m, 7H), 2.14(m, 2H), 1.89(m, 2H), 1.82(m, 2H), 1.71(br, 1H), 1.60(br, 1H), 1.41(br, 1H)

[0101] Example 22: (S)-Quinuclidin-3-yl (6-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1H-NMR (400MHz, CDCl 3 ) δ 7.66(m, 1H), 7.51~7.49(m, 2H), 7.41(m, 3H), 4.99(m, 2H), 4.80(br, 1H), 3.30(m, 1H), 2.87~2 .78(m, 7H), 2.13(m, 2H), 1.90(m, 2H), 1.82(m, 2H), 1.71(br, 1H), 1.61(br, 1H), 1.42(br, 1H)

[0102] Example 23: (S)-Quinuclidin-3-yl (6-(2,5-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.42(m, 2H), 7.32(s, 1H), 7.26(m, 2H), 7.15(s, 1H), 5.05(m, 1H), 4.97(m, 1H), 4.81(br, 1H), 3.28( m, 1H), 2.88~2.77(m, 7H), 2.13(m, 2H), 1.90~1.87(m, 4H), 1.70(br, 1H), 1.60(br, 1H), 1.41(br, 1H)

[0103] Example 24: (S)-Quinuclidin-3-yl (6-(3,5-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.57(m, 1H), 7.49(m, 1H), 7.44(s, 2H), 7.36(m, 1H), 7.34(m, 1H), 5.00(m, 2H), 4.81(br, 1H), 3.28(m, 1 H), 2.87~2.78(m, 7H), 2.13(m, 2H), 1.90(m, 2H), 1.84(m, 2H), 1.71(br, 1H), 1.61(br, 1H), 1.41(br, 1H)

[0104] Example 25: (S)-Quinuclidin-3-yl (6-(4-(2-methoxyethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.51(d, 2H), 7.40(m, 2H), 7.28(m, 1H), 7.01(d, 2H), 5.02(m, 1H), 4.95~4.81(m, 2H), 4.19(d, 2H), 3.81(d, 2H), 3 .79(s, 3H), 3.30(m, 1H), 2.90~2.80(m, 7H), 2.06(m, 4H), 1.99(m, 2H), 1.73(br, 1H), 1.63(br, 1H), 1.44(br, 1H)

[0105] Example 26: (S)-Quinuclidin-3-yl (6-(4-(methoxymethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.51(m, 2H), 7.40(m, 2H), 7.28(m, 1H), 7.12(d, 2H), 5.23(s, 2H), 5.07(m, 1H), 4.94~4.80(m, 2H), 3.52(s , 3H), 3.29(m, 1H), 2.86~2.78(m, 7H), 2.06(m, 2H), 1.88(m, 4H), 1.70(br, 1H), 1.60(br, 1H), 1.40(br, 1H)

[0106] Example 27: (S)-Quinuclidin-3-yl (6-(3-(2-methoxyethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.42(m, 2H), 7.37(m, 2H), 7.18(m, 2H), 6.94(d, 1H), 5.02(m, 1H), 4.95~4.82(m, 2H), 4.21(d, 2H), 3.80(d, 2H), 3.80(s, 3H), 3.31(m, 1H), 2.91~2.81(m, 7H), 2.31(br, 2H), 2.12(m, 2H), 1.89(m, 2H), 1.73(br, 1H), 1.62(br, 1H), 1.44(br, 1H)

[0107] Example 28: (S)-Quinuclidin-3-yl (6-(3-(methoxymethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.41(d, 2H), 7.36(m, 2H), 7.25(m, 2H), 7.05(d, 1H), 5.24(s, 2H), 5.12(m, 1H), 4.95~4.80(m, 2H), 3.52(s, 3H), 3 .28(m, 1H), 2.87~2.75(m, 7H), 2.50(br, 1H), 2.06(m, 2H), 1.88(m, 3H), 1.71(br, 1H), 1.60(br, 1H), 1.41(br, 1H)

[0108] Example 29: (S)-Quinuclidin-3-yl (6-(2-(2-methoxyethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.43~7.30(m, 5H), 7.04~6.99(m, 2H), 5.10(m, 1H), 4.95~4.80(m, 2H), 4.13(d, 2H), 3.71(d, 2H), 3.41(s, 3H), 3. 28(m, 1H), 2.88~2.79(m, 7H), 2.39(br, 1H), 2.06(m, 2H), 1.88(m, 3H), 1.71(br, 1H), 1.60(br, 1H), 1.42(br, 1H)

[0109] Example 30: (S)-Quinuclidin-3-yl (6-(2-(methoxymethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.38(d, 2H), 7.29(m, 2H), 7.24(m, 2H), 7.11(t, 1H), 5.15(s, 2H), 5.10(m, 1H), 4.96~4.79(m, 2H), 3.45(s, 3H), 3 .28(m, 1H), 2.88~2.77(m, 7H), 2.46(br, 1H), 2.06(m, 2H), 1.89(m, 3H), 1.71(br, 1H), 1.60(br, 1H), 1.42(br, 1H)

[0110] Example 31: (S)-Quinuclidin-3-yl (6-(4-ethylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.52(m, 2H), 7.43(m, 2H), 7.28(d, 3H), 5.14(m, 1H), 4.98~4.81(m, 2H), 3.30(m, 1H), 2.87(m, 7H) ), 2.70(q, 2H), 2.10(m, 2H), 1.89(m, 4H), 1.71(br, 1H), 1.61(br, 1H), 1.42(br, 1H), 1.29(t, 3H)

[0111] Example 32: (S)-Quinuclidin-3-yl (6-(4-propylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.51(d, 1H), 7.43(m, 2H), 7.27(m, 3H), 5.09(m, 1H), 4.96~4.80(m, 2H), 3.30(m, 1H), 2.87~2.76(m , 7H), 2.64(t, 2H), 2.10(m, 2H), 1.89(m, 3H), 1.74(m, 3H), 1.61(br, 1H), 1.42(br, 1H), 0.99(t, 3H)

[0112] Example 33: (S)-Quinuclidin-3-yl (6-(4-butylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1H-NMR (400MHz, CDCl 3 ) δ 7.51(d, 2H), 7.42(d, 2H), 7.27(m, 3H), 5.11(m, 1H), 4.96~4.81(m, 2H), 3.32(m, 1H), 2.87~2.78(m , 7H), 2.66(t, 2H), 2.10(m, 2H), 1.89(m, 3H), 1.72(br, 1H), 1.67(m, 3H), 1.43(m, 3H), 0.98(t, 3H)

[0113] Example 34: (S)-Quinuclidin-3-yl (6-(4-isopropylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.52(d, 2H), 7.42(m, 2H), 7.32(m, 3H), 5.05(m, 1H), 4.96~4.81(m, 2H), 3.30(m, 1H), 2.97(m, 1H), 2.87~2. 79(m, 7H), 2.26(br, 1H), 2.07(m, 2H), 1.89(m, 3H), 1.72(br, 1H), 1.61(br, 1H), 1.42(br, 1H), 1.25(d, 6H)

[0114] Example 35: (S)-Quinuclidin-3-yl (6-(4-isobutylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.50(d, 1H), 7.43(m, 3H), 7.33(s, 1H), 7.23(d, 2H), 5.10(m, 1H), 4.95~4.81(m, 2H), 3.30(m, 1H), 2.87~2 .78(m, 7H), 2.52(d, 2H), 2.08(m, 2H), 1.89(m, 4H), 1.70(br, 1H), 1.60(br, 1H), 1.40(br, 1H), 0.96(d, 6H)

[0115] Example 36: (S)-Quinuclidin-3-yl (6-(4-(tert-butyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.53(m, 1H), 7.51(m, 3H), 7.46(m, 2H), 7.33(s, 1H), 5.05(m, 1H), 4.96~4.81(m, 2H), 3.30(m, 1H), 2.88~2. 78(m, 7H), 2.31(br, 1H), 2.06(m, 2H), 1.88(m, 3H), 1.72(br, 1H), 1.61(br, 1H), 1.38(br, 1H), 1.28(s, 9H)

[0116] Example 37: (S)-Quinuclidin-3-yl (6-(4-cyclopropyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.48~7.41(m, 4H), 7.31(m, 1H), 7.15(m, 2H), 5.14(m, 1H), 4.94~4.80(m, 2H), 3.28(m, 1H), 2.86~2.78 (m, 7H), 2.08(m, 2H), 1.88(m, 4H), 1.71(br, 1H), 1.61(br, 1H), 1.41(br, 1H), 1.01(m, 2H), 0.75(m, 2H)

[0117] Example 38: (S)-Quinuclidin-3-yl (6-(3-ethylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.43(m, 4H), 7.33(m, 2H), 7.21(d, 1H), 5.10(m, 1H), 4.96~4.80(m, 2H), 3.30(m, 1H), 2.87~2.75(m , 7H), 2.74(q, 2H), 2.09(m, 2H), 1.89(m, 4H), 1.71(br, 1H), 1.0(br, 1H), 1.42(br, 1H), 1.30(t, 3H)

[0118] Example 39: (S)-Quinuclidin-3-yl (6-(3-(tert-butyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.58(s, 1H), 7.44(s, 2H), 7.42(m, 3H), 7.32(s, 1H), 5.03(m, 1H), 4.97~4.81(m, 2H), 3.30(m, 1H), 2 .89~2.80(m, 7H), 2.14(m, 2H), 1.90(m, 4H), 1.73(br, 1H), 1.60(br, 1H), 1.40(br, 1H), 1.39(s, 9H)

[0119] Example 40: (S)-Quinuclidin-3-yl (6-(3-isopropylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.44~7.33(m, 6H), 7.24(m, 1H), 5.11(m, 1H), 4.96~4.80(m, 2H), 3.30(m, 1H), 3.02(m, 1H), 2.88~2.75( m, 7H), 2.55(br, 1H), 2.14(m, 2H), 1.89(m, 3H), 1.71(br, 1H), 1.60(br, 1H), 1.41(br, 1H), 1.28(d, 6H)

[0120] Example 41: (S)-Quinuclidin-3-yl (6-(2-ethylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.40(m, 1H), 7.32(m, 3H), 7.23(m, 1H), 7.18(m, 1H), 7.05(s, 1H), 5.15(m, 1H), 4.97~4.81(m, 2H), 3.28(m, 1H), 2.88~2. 77(m, 7H), 2.62(q, 2H), 2.46(br, 1H), 2.06(m, 2H), 1.89(m, 3H), 1.71(br, 1H), 1.60(br, 1H), 1.41(br, 1H), 1.13(t, 3H)

[0121] Example 42: (S)-Quinuclidin-3-yl (6-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.45(t, 1H), 7.36(m, 1H), 7.25(m, 3H), 7.12(d, 1H), 5.07(m, 1H), 4.95~4.80(m, 2H), 3.29(m, 1H), 2 .87~2.78(m, 7H), 2.43(br, 1H), 2.13(m, 2H), 1.89(m, 3H), 1.71(br, 1H), 1.60(br, 1H), 1.41(br, 1H)

[0122] Example 43: (S)-Quinuclidin-3-yl (6-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.38(m, 2H), 7.28(m, 1H), 7.08(m, 2H), 6.93(d, 1H), 5.03(m, 1H), 4.91~4.80(m, 2H), 4.31(s, 4H) , 3.28(m, 1H), 2.22(br, 1H), 2.06(m, 2H), 1.87(m, 3H), 1.71(br, 1H), 1.61(br, 1H), 1.42(br, 1H)

[0123] Example 44: (S)-Quinuclidin-3-yl (6-(2,3-dihydrobenzofuran-6-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.42~7.27(m, 5H), 6.85(d, 1H), 5.05(m, 1H), 4.94~4.80(m, 2H), 4.63(t, 2H), 3.28(m, 3H), 2.86 ~2.78(m, 7H), 2.24(br, 1H), 2.06(m, 2H), 1.88(m, 3H), 1.71(br, 1H), 1.61(br, 1H), 1.41(br, 1H)

[0124] Example 45: (S)-Quinuclidin-3-yl (6-(4-morpholinophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.53(d, 2H), 7.40(m, 2H), 7.30(m, 1H), 6.98(d, 2H), 5.07(m, 1H), 4.95~4.79(m, 2H), 3.90(m, 4H), 3.31(m , 1H), 3.23(m, 4H), 2.86~2.77(m, 7H), 2.13(m, 2H), 1.88(m, 4H), 1.70(br, 1H), 1.59(br, 1H), 1.39(br, 1H)

[0125] Example 46: (S)-Quinuclidin-3-yl (6-(4-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.53(d, 2H), 7.40(m, 3H), 7.28(m, 1H), 6.98(d, 1H), 5.04(m, 1H), 4.95~4.81(m, 1H), 3.86(s, 3H), 3.29(m, 1H), 2.86~2.79(m, 7H), 2.30(br, 1H), 2.09(m, 2H), 1.88(m, 3H), 1.72(br, 1H), 1.61(br, 1H), 1.41(br, 1H)

[0126] Example 47: (S)-Quinuclidin-3-yl (6-(3-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.43(m, 2H), 7.36(m, 2H), 7.17(d, 1H), 7.10(s, 1H), 6.91(d, 1H), 5.07(m, 1H), 4.96~4.81(m, 2H), 3.88(s, 3H), 3 .31(m, 1H), 2.87~2.78(m, 7H), 2.38(br, 1H), 2.10(m, 2H), 1.89(m, 3H), 1.71(br, 1H), 1.60(br, 1H), 1.41(br, 1H)

[0127] Example 48: (S)-Quinuclidin-3-yl (6-(2-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.39(m, 2H), 7.31~7.28(m, 3H), 7.01(m, 2H), 5.06(m, 1H), 4.96~4.81(m, 2H), 3.83(s, 3H), 3.29(m, 1H) , 2.86~2.79(m, 7H), 2.30(br, 1H), 2.07(m, 2H), 1.88(m, 3H), 1.72(br, 1H), 1.62(br, 1H), 1.41(br, 1H)

[0128] Example 49: (S)-Quinuclidin-3-yl (6-(3-fluoropyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 8.53(s, 1H), 8.45(s, 1H), 7.48(m, 2H), 7.38(m, 2H), 5.13(m, 1H), 4.97~4.79(m, 2H), 3.26(m , 1H), 2.86~2.76(m, 7H), 2.05(m, 2H), 1.81(m, 4H), 1.70(br, 1H), 1.59(br, 1H), 1.40(br, 1H)

[0129] Example 50: (S)-Quinuclidin-3-yl (6-(2-methylpyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 8.54(m, 1H), 7.68(m, 1H), 7.47(m, 2H), 7.37(m, 2H), 4.99(m, 2H), 4.80(m, 1H), 3.29(m, 1H), 2.8 8~2.79(m, 7H), 2.63(s, 3H), 2.09(m, 2H), 1.89(m, 4H), 1.72(br, 1H), 1.61(br, 1H), 1.41(br, 1H)

[0130] Example 51: (S)-Quinuclidin-3-yl (6-(2-methoxypyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 8.21(s, 1H), 7.44(, 2H), 7.35(s, 1H), 7.08(s, 1H), 6.93(m, 1H), 5.04(m, 1H), 4.96~4.79(m, 2H), 3.99(s, 3H), 3.27(m, 1H), 2.86~2,76(m, 7H), 2.06(m, 2H), 1.89(m, 4H), 1.70(br, 1H), 1.58(br, 1H), 1.40(br, 1H)

[0131] Example 52: (S)-Quinuclidin-3-yl (6-(1H-pyrrolo[2,3-b]pyridin-5-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1H-NMR (400MHz, CDCl 3 ) δ 9.64(br, 1H), 8.11(s, 1H), 7.45(m, 2H), 7.31(m, 1H), 7.12(m, 2H), 6.56(s, 1H), 5.21(m, 1H), 4.97~4.81(m , 2H), 3.29(m, 1H), 3.87~2.79(m, 7H), 2.06(m, 2H), 1.90(m, 4H), 1.71(br, 1H), 1.62(br, 1H), 1.42(br, 1H)

[0132] Example 53: (S)-Quinuclidin-3-yl (6-(pyrimidin-5-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 9.20(s, 1H), 8.92(s, 2H), 7.67(m, 1H), 7.49(m, 1H), 7.40(m, 1H), 5.09(m, 1H), 4.98~4.80(m, 2H), 3 .28(m, 1H), 2.87~2.77(m, 7H), 2.06(m, 2H), 1.91(m, 4H), 1.70(br, 1H), 1.59(br, 1H), 1.40(br, 1H)

[0133] Example 54: (S)-Quinuclidin-3-yl (6-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 9.84(br, 1H), 8.37(s, 1H), 7.60(m, 1H), 7.54(s, 2H), 7.40(s, 1H), 7.18(m, 1H), 6.71(s, 1H), 5.10(m, 1H), 5.01~ 4.83(m, 2H), 3.32(m, 1H), 2.90~2.84(m, 7H), 2.14(m, 2H), 1.93(m, 4H), 1.73(br, 1H), 1.62(br, 1H), 1.43(br, 1H)

[0134] Examples 55 to 85 The title compounds of Examples 55 to 85 were prepared according to the same procedure as in Example 1 using (S)-quinuclidin-3-yl (7-bromo-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate prepared in Preparation Example 2 and the corresponding substituted boronic acids, respectively.

[0135] Example 55: (S)-Quinuclidin-3-yl (7-(4-fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.52(d, 2H), 7.37(d, 1H), 7.28(m, 1H), 7.17(d, 1H), 7.11(m, 2H), 4.98(m, 2H), 4.78(m, 1H), 3.25(m, 1H) ), 2.83~2.70(m, 7H), 2.04(m, 2H), 1.89(m, 3H), 1.78(br, 1H), 1.68(br, 1H), 1.57(br, 1H), 1.37(br, 1H)

[0136] Example 56: (S)-Quinuclidin-3-yl (7-(4-chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.50(m, 3H), 7.39(m, 3H), 7.17(d, 1H), 4.99(m, 2H), 4.78(m, 1H), 3.25(m, 1H), 2.83~2.70 (m, 7H), 2.05 (m, 2H), 1.88 (m, 3H), 1.79 (br, 1H), 1.68 (br, 1H), 1.59 (br, 1H), 1.37 (br, 1H)

[0137] Example 57: (S)-Quinuclidin-3-yl (7-(p-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.44(m, 3H), 7.23(m, 2H), 7.15(m, 2H), 5.10(m, 1H), 4.93(m, 1H), 4.76(m, 1H), 2.27(m, 1H), 2.86~2 .72(m, 7H), 2.38(s, 3H), 2.11(m, 3H), 1.99~1.86(m, 3H), 1.66(br, 1H), 1.56(br, 1H), 1.37(br, 1H)

[0138] Example 58: (S)-Quinuclidin-3-yl (7-(3-(fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.56(d, 1H), 7.41(m, 2H), 7.35(m, 2H), 7.18(m, 1H), 7.04(m, 1H), 5.13(m, 1H), 4.97(m, 1H), 4.60(m, 1H), 3.28(m, 1H) ), 2.85~2.75(m, 7H), 2.24(m, 1H), 2.08(m, 1H), 1.89(m, 3H), 1.81(br, 1H), 1.69(br, 1H), 1.58(br, 1H), 1.39(br, 1H)

[0139] Example 59: (S)-Quinuclidin-3-yl (7-(3-(chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.54(s, 2H), 7.40~7.28(m, 4H), 7.20(m, 1H), 5.13(m, 1H), 4.97(m, 1H), 4.78(m, 1H), 3.28(m, 1H), 2.85~2. 75(m, 7H), 2.35(br, 1H), 2.08(m, 1H), 1.89(m, 3H), 1.81(br, 1H), 1.69(br, 1H), 1.59(br, 1H), 1.40(br, 1H)

[0140] Example 60: (S)-Quinuclidin-3-yl (7-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.78(m, 1H), 7.73(m, 1H), 7.55(m, 3H), 7.42(m, 1H), 7.20(d, 1H), 5.00(m, 2H), 4.78(m, 1H), 3.26(m, 1H) ), 2.84~2.71(m, 7H), 2.11(m, 4H), 1.96(m, 1H), 1.79(br, 1H), 1.69(br, 1H), 1.58(br, 1H), 1.39(br, 1H)

[0141] Example 61: (S)-Quinuclidin-3-yl (7-(2-(fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.51(m, 1H), 7.41(m, 2H), 7.31(m, 1H), 7.22(m, 3H), 5.20(m, 1H), 4.97(m, 1H), 4.76(m, 1H), 3.26(m, 1H), 2.84 ~2.69(m, 7H), 2.31(br, 1H), 2.08(m, 1H), 1.88(m, 3H), 1.80(br, 1H), 1.68(br, 1H), 1.57(br, 1H), 1.37(br, 1H)

[0142] Example 62: (S)-Quinuclidin-3-yl (7-(2-chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.44(m, 2H), 7.30(m, 4H), 7.16(d, 1H), 5.17(m, 1H), 4.93(m, 1H), 4.73(m, 1H), 3.20(m, 1H), 2.84 ~2.67(m, 7H), 2.09(m, 3H), 1.87(m, 2H), 1.77(br, 1H), 1.65(br, 1H), 1.54(br, 1H), 1.35(br, 1H)

[0143] Example 63: (S)-Quinuclidin-3-yl (7-(2-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.73(m, 1H), 7.56(m, 1H), 7.45(m, 1H), 7.30(m, 2H), 7.13(m, 2H), 5.12(m, 1H), 4.92(m, 1H), 4.71(m, 1H), 3.20 (m, 1H), 2.82~2.68(m, 7H), 2.09(m, 3H), 1.87(m, 2H), 1.77(br, 1H), 1.64(br, 1H), 1.53(br, 1H), 1.33(br, 1H)

[0144] Example 64: (S)-Quinuclidin-3-yl (7-(3,4-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.50(m, 1H), 7.34(m, 2H), 7.26~7.16(m, 3H), 5.11(m, 1H), 4.94(m, 1H), 4.76(m, 1H), 3.26(m, 1H), 2 .82~2.69(m, 7H), 2.02(m, 3H), 1.87(m, 2H), 1.78(br, 1H), 1.68(br, 1H), 1.56(br, 1H), 1.36(br, 1H)

[0145] Example 65: (S)-Quinuclidin-3-yl (7-(2,4-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.45(m, 1H), 7.36(m, 2H), 7.16(d, 1H), 6.92(m, 2H), 5.13(m, 1H), 4.94(m, 1H), 4.75(m, 1H), 3.22(m, 1H) ), 2.83~2.68(m, 7H), 2.11(m, 3H), 1.87(m, 2H), 1.77(br, 1H), 1.66(br, 1H), 1.55(br, 1H), 1.35(br, 1H)

[0146] Example 66: (S)-Quinuclidin-3-yl (7-(2,4,5-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.44(m, 1H), 7.30~7.17(m, 3H), 7.01(m, 1H), 5.12(m, 1H), 4.93(m, 1H), 4.75(m, 1H), 3.22(m, 1H), 2 .83~2.68(m, 7H), 2.05(m, 3H), 1.88(m, 2H), 1.77(br, 1H), 1.66(br, 1H), 1.56(br, 1H), 1.36(br, 1H)

[0147] Example 67: (S)-Quinuclidin-3-yl (7-(2,5-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.50(d, 1H), 7.35(m, 1H), 7.18(d, 1H), 7.11(m, 2H), 6.98(m, 1H), 5.18(m, 1H), 4.95(m, 1H), 4.78(m, 1H), 3.25(m, 1H) ), 2.85~2.73(m, 7H), 2.28(br, 1H), 2.08(m, 1H), 1.89(m, 3H), 1.80(br, 1H), 1.67(m, 1H), 1.57(br, 1H), 1.38(br, 1H)

[0148] Example 68: (S)-Quinuclidin-3-yl (7-(3,5-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.52(m, 1H), 7.37(m, 1H), 7.19(d, 1H), 7.08(m, 2H), 6.78(m, 1H), 5.08(m, 1H), 4.97(m, 1H), 4.80(m, 1H), 3.28(m, 1H) ), 2.85~2.76(m, 7H), 2.09(m, 2H), 1.93(m, 1H), 1.89(m, 2H), 1.81(br, 1H), 1.69(br, 1H), 1.60(br, 1H), 1.40(br, 1H)

[0149] Example 69: (S)-Quinuclidin-3-yl (7-(2,3,4-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.43(m, 1H), 7.28(m, 1H), 7.18(d, 1H), 7.10(m, 1H), 7.03(m, 1H), 5.27(m, 1H), 4.94(m, 1H), 4.76(m, 1H), 3.23 (m, 1H), 2.82~2.66(m, 7H), 2.07(m, 3H), 1.88(m, 2H), 1.81(br, 1H), 1.67(br, 1H), 1.56(br, 1H), 1.37(br, 1H)

[0150] Example 70: (S)-Quinuclidin-3-yl (7-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.63(s, 1H), 7.48(m, 2H), 7.38(m, 2H), 7.18(d, 1H), 5.14(m, 1H), 4.94(m, 1H), 4.76(m, 1H), 3.22(m, 1H) ), 2.83~2.68(m, 7H), 2.06(m, 2H), 1.87(m, 3H), 1.78(br, 1H), 1.67(m, 1H), 1.56(br, 1H), 1.37(br, 1H)

[0151] Example 71: (S)-Quinuclidin-3-yl (7-(2,5-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.40(m, 2H), 7.32(m, 1H), 7.27(m, 2H), 7.17(m, 1H), 5,12(m, 1H), 4.96(m, 1H), 4.76(m, 1H), 3.26(m, 1H) ), 2.85~2.69(m, 7H), 2.11(m, 3H), 1.89(m, 2H), 1.78(br, 1H), 1.67(br, 1H), 1.58(br, 1H), 1.40(br, 1H)

[0152] Example 72: (S)-Quinuclidin-3-yl (7-(pyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 8.65(s, 2H), 7.62(m, 1H), 7.50(m, 3H), 7.25(d, 1H), 5.02(m, 2H), 4.81(br, 1H), 3.30(m, 1) H), 2.87~2.72(m, 7H), 2.13(m, 2H), 1.90(m, 4H), 1.71(br, 1H), 1.61(br, 1H), 1.41(br, 1H)

[0153] Example 73: (S)-Quinuclidin-3-yl (7-(pyridin-3-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 8.82(s, 1H), 8.59(s, 1H), 7.87(m, 1H), 7.58(m, 1H), 7.44(m, 1H), 7.42(m, 1H), 7.24(d, 1H), 5.07(m, 2H), 4.80(br , 1H), 3.27(m, 1H), 2.87~2.78(m, 7H), 2.09~1.99(m, 5H), 1.82(br, 1H), 1.71(br, 1H), 1.61(br, 1H), 1.41(br, 1H)

[0154] Example 74: (S)-Quinuclidin-3-yl (7-(o-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.34(m, 1H), 7.26(m, 4H), 7.17(s, 2H), 4.99(m, 2H), 4.77(m, 1H), 3.29(m, 1H), 2.85~2.73(m, 7H) , 2.30(s, 3H), 2.14(m, 4H), 1,90(br, 1H), 1.80(br, 1H), 1.69(br, 1H), 1.58(br, 1H), 1.40(br, 1H)

[0155] Example 75: (S)-Quinuclidin-3-yl (7-(2-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.51(m, 1H), 7.38(d, 1H), 7.31(m, 2H), 7.16(d, 1H), 7.05~6.99(m, 2H), 5.01(m, 1H), 4,97(m, 1H), 4.77(br, 1H), 3.83(s, 3H), 3.25(m, 1H), 2.84~2.76(m, 7H), 2.04(m, 2H), 1.88(m, 4H), 1.69(br, 1H), 1.58(br, 1H), 1.40(br, 1H)

[0156] Example 76: (S)-Quinuclidin-3-yl (7-(2-ethoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.59(d, 1H), 7.43(m, 1H), 7.32(m, 2H), 7.15(d, 1H), 7.03~6.97(m, 2H), 5.00(m, 1H), 4.97(m, 1H), 4.76(br, 1H), 4.07(m, 2H), 3.26(m, 1H), 2.85~2.76(m, 7H), 2.06(m, 2H), 1.89(m, 4H), 1.69(br, 1H), 1.59(br, 1H), 1.38(t, 4H)

[0157] Example 77: (S)-Quinuclidin-3-yl (7-(3-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.57(m, 1H), 7.50~7.48(m, 1H), 7.42(m, 1H), 7.18(m, 2H), 7.14(m, 1H), 6.88(d, 1H), 4.99(m, 2H), 4.79(m, 1H), 3.83(s, 3H), 3.28(m, 1H), 2.85~2.78(m, 7H), 2.06(m, 2H), 1.89(m, 3H), 1.82(br, 1H), 1.59(br, 1H), 1.71(br, 1H), 1.48(br, 1H)

[0158] Example 78: (S)-Quinuclidin-3-yl (7-(2-isopropoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.60(m, 1H), 7.41(d, 1H), 7.31(m, 2H), 7.13(d, 1H), 6.99(t, 1H), 4.99(m, 1H), 4.93(m, 1H), 4.77(br, 1H), 4.54(m, 1H), 3.2 8(m, 1H), 2.84~2.75(m, 7H), 2.13(m, 2H), 2.06(m, 3H), 1.89(m, 1H), 1.82(br, 1H), 1.70(br, 1H), 1.38(br, 1H), 1.31(d, 6H)

[0159] Example 79: (S)-Quinuclidin-3-yl (7-(4-(2-methoxyethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.67(m, 1H), 7.50(m, 3H), 7.40(m, 1H), 7.17(m, 1H), 7.01(m, 1H), 5.02(m, 1H), 4.97~4.78(m, 2H), 4.18(s, 2H), 3.79(s , 2H), 3.48(s, 3H), 3.29(m, 1H), 2.84~2.76(m, 7H), 2.05(m, 3H), 1.88(m, 3H), 1.70(br, 1H), 1.59(br, 1H), 1.38(br, 1H)

[0160] Example 80: (S)-Quinuclidin-3-yl (7-(4-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.52(m, 3H), 7.41(m, 1H), 7.17(m, 1H), 6.99(m, 2H), 5.04(m, 1H), 4.97(m, 1H), 4.79(m, 1H), 3.86(s, 3H) ), 3.30(m, 1H), 2.88~2.74(m, 7H), 2.13(m, 3H), 1.92(m, 3H), 1.70(br, 1H), 1.60(br, 1H), 1.40(br, 1H)

[0161] Example 81: (S)-Quinuclidin-3-yl (7-(4-ethoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.50(m, 3H), 7.40(d, 1H), 7.16(m, 1H), 6.97(m, 2H), 5.04(m, 1H), 4.97(m, 1H), 4.80(m, 1H), 4.10(m, 2H), 3.3 0(m, 1H), 2.88~2.74(m, 7H), 2.06(m, 2H), 1.98(m, 4H), 1.70(br, 1H), 1.60(br, 1H), 1.40(br, 1H), 1.39(t, 3H)

[0162] Example 82: (S)-Quinuclidin-3-yl (7-(4-propoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.53(m, 3H), 7.41(d, 1H), 7.17(m, 1H), 6.98(m, 2H), 5.01(m, 1H), 4.97(m, 1H), 4.79(m, 1H), 3.97(m, 2H), 3.2 8(m, 1H), 2.87~2.76(m, 7H), 2.06(m, 2H), 1.84(m, 6H), 1.69(br, 1H), 1.61(br, 1H), 1.40(br, 1H), 1.08(t, 3H)

[0163] Example 83: (S)-Quinuclidin-3-yl (7-(4-isopropoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.52(m, 3H), 7.39(d, 1H), 7.16(d, 1H), 6.97(m, 2H), 5.04(m, 1H), 4.97(m, 1H), 4.79(m, 1H), 4.59(m, 1H), 3.27(m , 1H), 2.84~2.71(m, 7H), 2.05(m, 2H), 1.93~1.82(m, 4H), 1.70(br, 1H), 1.60(br, 1H), 1.38(br, 1H), 1.17(d, 6H)

[0164] Example 84: (S)-Quinuclidin-3-yl (7-(benzo[d]dioxol-5-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.50(m, 1H), 7.35(m, 1H), 7.16(d, 1H), 7.05(m, 2H), 6.89(m, 1H), 6.01(s, 2H), 5.02(m, 1H), 4.96(m, 1H), 4.7 8(m, 1H), 3.31(m, 1H), 2.87~2.72(m, 7H), 2.06(m, 2H), 1.88(m, 4H), 1.70(br, 1H), 1.60(br, 1H), 1.28(br, 1H)

[0165] Example 85: (S)-Quinuclidin-3-yl (7-(m-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.57~7.38(m, 5H), 7.18(m, 2H), 5.01(m, 2H), 4.78(m, 1H), 3.29(m, 1H), 2.86~2.76(m, 7H), 2.43(s, 3H), 2.08(m, 2H), 1.89(m, 4H), 1.62(br, 1H), 1.59(br, 1H), 1.38(br, 1H)

[0166] Examples 86 to 150 The title compounds of Examples 86 to 150 were prepared according to the same procedure as in Example 1 using (S)-quinuclidin-3-yl (6-bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate prepared in Preparation Example 3 and the corresponding substituted boronic acids, respectively.

[0167] Example 86: (S)-Quinuclidin-3-yl (6-(4-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.53(m, 3H), 7.36(m, 2H), 7.13(t, 2H), 4.91(m, 2H), 4.65(m, 1H), 3.37(m, 1H), 3.05~2.85(m, 7 H), 2.29(m, 1H), 1.96(m, 1H), 1.83(m, 1H), 1.72(m, 3H), 1.36(m, 1H), 1.17(m, 3H), 1.00(s, 3H)

[0168] Example 87: (S)-Quinuclidin-3-yl (6-(4-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.50(m, 2H), 7.41(m, 2H), 7.31(m, 3H), 4.90(m, 2H), 4.67(m, 1H), 3.44(m, 1H), 3.13~3.88(m, 7 H), 2.20(m, 1H), 2.00(m, 1H), 1.87(m, 1H), 1.77(m, 1H), 1.66(m, 3H), 1.08(m, 3H), 1.00(s, 3H)

[0169] Example 88: (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.69(s, 4H), 7.48(m, 1H), 7.38(m, 2H), 4.94~4.87(m, 2H), 4.68(m, 1H), 3.40(m, 1H), 3.11~2.90( m, 7H), 2.26(m, 1H), 1.85(m, 1H), 1.73(m, 1H), 1.58(m, 3H), 1.40(m, 1H), 1.08(m, 3H), 0.99(m, 3H)

[0170] Example 89: (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(4-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1H-NMR (400MHz, CDCl 3 ) δ 7.68(m, 1H), 7.58(m, 2H), 7.50(m, 1H), 7.39(m, 1H), 7.30(m, 2H), 4.86(m, 2H), 4.68(m, 1H), 3.32(m, 1H), 3.00~2.84 (m, 7H), 2.31(br, 1H), 2.15(m, 1H), 1.91(m, 1H), 1.73(br, 1H), 1.66(m, 2H), 1.50(br, 1H), 1.08(m, 3H), 0.99(m, 3H)

[0171] Example 90: (S)-Quinuclidin-3-yl (6-(3-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.68(m, 2H), 7.57(m, 1H), 7.49(m, 1H), 7.42(m, 3H), 7.05(m, 1H), 4.86(m, 2H), 4.68(m, 1H), 3.37(m, 1H), 3.0 0~2.88(m, 7H), 2.16(m, 2H), 1.95(br, 1H), 1.77(br, 1H), 1.64(m, 2H), 1.52(br, 1H), 1.08(m, 3H), 0.99(m, 3H)

[0172] Example 91: (S)-Quinuclidin-3-yl (6-(3-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.55(s, 1H), 7.45(m, 1H), 7.31(m, 5H), 4.85(m, 2H), 4.68(m, 1H), 3.31(m, 1H), 2.96~2.83(m, 7H), 2.33 (m, 1H), 2.26(m, 1H), 1.92(br, 1H), 1.73(m, 2H), 1.68(br, 1H), 1.51(br, 1H), 1.08(m, 3H), 0.98(m, 3H)

[0173] Example 92: (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.82(s, 1H), 7.71(m, 1H), 7.60(m, 1H), 7.48~7.35(m, 4H), 4.84(m, 2H), 4.68(m, 1H), 3.37(m, 1H), 2.99~2.83(m, 7H), 2.20(m, 2H), 2.04(br, 1H), 1.71(m, 3H), 1.52(br, 1H), 1.08(m, 3H), 0.99(m, 3H)

[0174] Example 93: (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(3-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.71(m, 2H), 7.65(m, 2H), 7.43(m, 2H), 7.20(m, 1H), 4.85(m, 2H), 4.68(m, 1H), 3.40(m, 1H), 3.06~2.61(m, 7H) ), 2.22(m, 1H), 2.10(s, 1H), 1.96(m, 1H), 1.82(br, 1H), 1.73(m, 2H), 1.58(br, 1H), 1.08(m, 3H), 0.99(m, 3H)

[0175] Example 94: (S)-Quinuclidin-3-yl (6-(2-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.69(m, 1H), 7.40(m, 1H), 7.35(m, 3H), 7.21(m, 1H), 7.15(m, 1H), 4.89(m, 2H), 4.68(m, 1H), 3.38(m, 1H), 3.05~2.71 (m, 7H), 2.22(br, 1H), 2.10(s, 1H), 1.96(m, 1H), 1.80(br, 1H), 1.71(m, 2H), 1.55(br, 1H), 1.08(m, 3H), 0.99(m, 3H)

[0176] Example 95: (S)-Quinuclidin-3-yl (6-(2-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.48(d, 1H), 7.32(m, 5H), 7.19(s, 1H), 4.87(m, 2H), 4.67(m, 1H), 3.37(m, 1H), 2.99~2.86(m, 7 H), 2.38(m, 2H), 2.34(m, 1H), 1.93(m, 1H), 1.76(m, 2H), 1.52(br, 1H), 1.08(m, 3H), 0.99(m, 3H)

[0177] Example 96: (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(2-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.74(m, 1H), 7.55(m, 1H), 7.48(m, 1H), 7.33(m, 2H), 7.15(m, 1H), 7.07(s, 1H), 4.92(m, 2H), 4.68(m, 1H), 3.40(m, 1H), 3. 08~2.62(m, 7H), 2.26(m, 1H), 2.10(s, 1H), 1.99(m, 1H), 1.82(m, 1H), 1.73(m, 2H), 1.58(br, 1H), 1.08(m, 3H), 0.99(m, 3H)

[0178] Example 97: (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(2-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.71(m, 1H), 7.57(m, 1H), 7.49(m, 1H), 7.42(m, 1H), 7.37(m, 2H), 7.21(s, 1H), 4.89(m, 2H), 4.68(m, 1H), 3.33(m, 1H), 2.99~2.86(m, 7H), 2.31(m, 1H), 2.18(m, 1H), 1.99(m, 1H), 1.75(m, 3H), 1.52(m, 1H), 1.08(m, 3H), 0.99(m, 3H)

[0179] Example 98: (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(p-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.69(m, 1H), 7.49(m, 3H), 7.35(s, 1H), 7.24(m, 2H), 5.39(m, 2H), 4.67(m, 1H), 3.38(m, 1H), 3.00~2.87 (m, 7H), 2.41(s, 3H), 2.04(m, 3H), 1.96(br, 1H), 1.73(br, 2H), 1.50(br, 1H), 1.08(m, 3H), 0.97(m, 3H)

[0180] Example 99: (S)-Quinuclidin-3-yl (6-(4-(difluoromethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.57(m, 2H), 7.39(m, 2H), 7.29(m, 1H), 7.20(d, 2H), 6.75~6.38(t, 1H), 4.88(m, 2H), 4.66(m, 1H), 3.37(m, 1H) ), 2.98(m, 7H), 2.24(br, 1H), 1.95(br, 1H), 1.76(br, 1H), 1.72(m, 3H), 1.50(m, 1H), 1.07(m, 3H), 1.00(m, 3H)

[0181] Example 100: (S)-Quinuclidin-3-yl (6-(3,4-difluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.71(m, 1H), 7.50(m, 1H), 7.39(m, 3H), 7.20(m, 1H), 4.85(m, 2H), 4.67(m, 1H), 3.36(m, 1H), 3.00~2.84(m, 7H) ), 2.33(br, 1H), 2.17(m, 1H), 1.90(m, 1H), 1.77(m, 2H), 1.70(br, 1H), 1.51(br, 1H), 1.08(m, 3H), 0.99(m, 3H)

[0182] Example 101: (S)-Quinuclidin-3-yl (6-(2,4-difluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.71(m, 1H), 7.50(m, 1H), 7.38(m, 2H), 6.94(m, 2H), 4.85(m, 2H), 4.68(m, 1H), 3.37(m, 1H), 3.02~2.78(m, 7H) ), 2.48(br, 1H), 2.18(m, 1H), 2.10(s, 1H), 1.92(br, 1H), 1.77(m, 2H), 1.52(br, 1H), 1.08(m, 3H), 0.99(m, 3H)

[0183] Example 102: (S)-Quinuclidin-3-yl (6-(2,3-difluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.70(m, 1H), 7.66(m, 1H), 7.49(m, 1H), 7.35(d, 1H), 7.15(m, 2H), 4.88(m, 2H), 4.68(m, 1H), 3.33(m, 1H), 3.01 ~2.81(m, 7H), 2.59(br, 1H), 2.25(br, 1H), 1.82(br, 1H), 1.76(m, 3H), 1.50(br, 1H), 1.08(m, 3H), 0.99(m, 3H)

[0184] Example 103: (S)-Quinuclidin-3-yl (6-(2,5-difluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.69~7.49(m, 1H), 7.35(m, 2H), 7.13(m, 2H), 7.01(m, 1H), 4.90(m, 2H), 4.68(m, 1H), 3.29(m, 1H), 3.04~2.81(m , 7H), 2.22(m, 1H), 2.15(m, 1H), 1.99(m, 1H), 1.81(br, 1H), 1.72(m, 2H), 1.53(br, 1H), 1.08(m, 3H), 0.99(m, 3H)

[0185] Example 104: (S)-Quinuclidin-3-yl (6-(3,5-difluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.68~7.49(m, 1H), 7.39(m, 2H), 7.09(m, 2H), 6.79(m, 1H), 4.94(m, 2H), 4.67(m, 1H), 3.43(m, 1H), 3.02~2.88(m, 7H), 2.28(m, 1H), 2.16(m, 1H), 1.99(br, 1H), 1.86(br, 1H), 1.72(m, 2H), 1.50(br, 1H), 1.08(m, 3H), 0.99(m, 3H)

[0186] Example 105: (S)-Quinuclidin-3-yl (6-(2,5-dichlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.71(m, 2H), 7.57(m, 1H), 7.50(m, 2H), 7.25(m, 1H), 4.89(m, 2H), 4.66(m, 1H), 3.33(m, 1H), 3.02~2.86 (m, 7H), 2.37(br, 2H), 2.10(br, 1H), 1.92(br, 1H), 1.77(m, 2H), 1.50(br, 1H), 1.08(m, 3H), 0.99(m, 3H)

[0187] Example 106: (S)-Quinuclidin-3-yl (6-(3,4-dichlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.71(m, 2H), 7.55(m, 1H), 7.50(m, 2H), 7.38(m, 1H), 4.86(m, 2H), 4.68(m, 1H), 3.39(m, 1H), 3.04~2.88 (m, 7H), 2.26(m, 2H), 2.04(br, 1H), 1.99(br, 1H), 1.78(m, 2H), 1.53(br, 1H), 1.08(m, 3H), 0.99(m, 3H)

[0188] Example 107: (S)-Quinuclidin-3-yl (6-(3,5-dichlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.71(m, 1H), 7.56(m, 1H), 7.50(m, 2H), 7.34(m, 2H), 4.85(m, 2H), 4.68(m, 1H), 3.31(m, 1H), 2.98~2.8 6(m, 7H), 2.14(m, 2H), 1.94(br, 1H), 1.73(m, 2H), 1.65(m, 1H), 1.51(m, 1H), 1.08(m, 3H), 0.99(m, 3H)

[0189] Example 108: (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(2,4,5-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.69(m, 1H), 7.55(m, 1H), 7.38(m, 1H), 7.26(m, 1H), 7.02(m, 1H), 4.86(m, 2H), 4.67(m, 1H), 3.30(m, 1H), 2.95 ~2.87(m, 7H), 2.51(br, 2H), 2.08(br, 1H), 1.73(br, 1H), 1.64(m, 2H), 1.49(br, 1H), 1.06(m, 3H), 0.98(m, 3H)

[0190] Example 109: (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(2,3,4-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.68(m, 1H), 7.54~7.48(m, 1H), 7.32(m, 1H), 7.24(m, 1H), 7.12(m, 1H), 4.91(m, 2H), 4.67(m, 1H), 3.44(m, 1H) , 3.07(m, 7H), 2.27(br, 2H), 2.10(br, 1H), 1.99(br, 1H), 1.73(m, 2H), 1.63(br, 1H), 1.08(m, 3H), 0.98(m, 3H)

[0191] Example 110: (S)-Quinuclidin-3-yl (6-(4-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.29~7.24(m, 2H), 7.18(d, 2H), 7.11(m, 1H), 6.98(d, 2H), 4.85(m, 1H) ), 4.80(br, 1H), 4.66(m, 1H), 4.17(m, 2H), 3.79(m, 2H), 3.48(s, 3H), 3 .25(m, 1H), 2.88~2.76(m, 5H), 2.59(m, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 3H), 1.40(br, 1H), 1.05(d, 3H), 0.96(d, 3H)

[0192] Example 111: (S)-Quinuclidin-3-yl (6-(3-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.33~7.23(m, 3H), 7.11(m, 1H), 6.91(d, 1H), 6.85(m, 2H), 4.85(m, 1H) ), 4.80(br, 1H), 4.66(m, 1H), 4.15(m, 2H), 3.78(m, 2H), 3.47(s, 3H), 3 .25(m, 1H), 2.88~2.76(m, 5H), 2.59(m, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 3H), 1.40(br, 1H), 1.05(d, 3H), 0.96(d, 3H)

[0193] Example 112: (S)-Quinuclidin-3-yl (6-(2-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.32~7.21(m, 3H), 7.10(m, 1H), 7.07(m, 2H), 6.96(d, 1H), 4.88(m, 1H) , 4.79(br, 1H), 4.66(m, 1H), 4.12~3.99(m, 2H), 3.53(m, 2H), 3.25(m, 1H) ), 3.22(m, 3H), 2.88~2.76(m, 5H), 2.39(m, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 3H), 1.40(br, 1H), 1.05(d, 3H), 0.96(d, 3H)

[0194] Example 113: (S)-Quinuclidin-3-yl (6-(4-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.31(m, 2H), 7.19(d, 2H), 7.09(m, 3H), 5.23(s, 2H), 4.88(m, 1H), 4.79(br, 1H), 4.66(m, 1H), 3.31(s, 3H), 3.25(m, 1H), 3.22(m, 3H) ), 2.88~2.76(m, 5H), 2.39(m, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 3H), 1.40(br, 1H), 1.05(d, 3H), 0.96(d, 3H)

[0195] Example 114: (S)-Quinuclidin-3-yl (6-(3-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.33~7.23(m, 3H), 7.11(m, 1H), 6.91(d, 1H), 6.85(m, 2H), 5.20(s, 2H) ), 4.88(m, 1H), 4.79(br, 1H), 4.66(m, 1H), 3.30(s, 3H), 3.25(m, 1H), 3 .22(m, 3H), 2.88~2.76(m, 5H), 2.39(m, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 3H), 1.40(br, 1H), 1.05(d, 3H), 0.96(d, 3H)

[0196] Example 115: (S)-Quinuclidin-3-yl (6-(2-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.32(m, 1H), 7.31~7.13(m, 3H), 7.08(m, 3H), 5.05(s, 2H), 4.88(m, 1H), 4.79(br, 1H), 4.66(m, 1H), 3.34~3.31(m, 3H), 3.29(m, 1H), 3.22 (m, 3H), 2.88~2.76(m, 5H), 2.39(m, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 3H), 1.40(br, 1H), 1.05(d, 3H), 0.96(d, 3H)

[0197] Example 116: (S)-Quinuclidin-3-yl (6-(2-methoxypyridin-4-yl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 8.20(d, 1H), 7.37(m, 1H), 7.27(m, 1H), 7.06(m, 1H), 6.79(m, 1H), 6.66(s, 1H), 4.87(m, 1H), 4.77(m, 1H), 4.65(m, 1H), 3.98(s, 3H), 3.25 (m, 1H), 2.88~2.76(m, 5H), 2.58(m, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 3H), 1.40(br, 1H), 1.04(m, 3H), 0.96(m, 3H)

[0198] Example 117: (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(2-methylpyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 8.54(d, 1H), 7.36(m, 1H), 7.27(s, 2H), 7.04(s, 1H), 7.02(d, 1H), 4.87(m, 1H), 4.77(m, 1H), 4.65(m, 1H), 3.25(m, 1H), 2.88~2.76 (m, 5H), 2.57(s, 3H), 2.56(m, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 3H), 1.40(br, 1H), 1.05(m, 3H), 0.97(m, 3H)

[0199] Example 118: (S)-Quinuclidin-3-yl (6-(2-fluoropyridin-4-yl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 8.26(d, 1H), 7.38(m, 1H), 7.27(m, 2H), 7.08(m, 1H), 7.07(m, 1H), 6.84(s, 1H), 4.87(m, 1H), 4.77(m, 1H), 4.65(m, 1H), 3.25(m, 1H) ), 2.88~2.76(m, 5H), 2.56(m, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 3H), 1.40(br, 1H), 1.05(m, 3H), 0.96(m, 3H)

[0200] Example 119: (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(2-(trifluoromethyl)pyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 8.78(d, 1H), 7.62(s, 1H), 7.44(m, 2H), 7.31(m, 1H), 7.09(m, 1H), 4.87(m, 1H), 4.77(m, 1H), 4.65(m, 1H), 3.25(m, 1H), 2.88 ~2.76(m, 5H), 2.56(m, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 3H), 1.40(br, 1H), 1.07(m, 3H), 0.96(m, 3H)

[0201] Example 120: (S)-Quinuclidin-3-yl (6-(4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.32(m, 2H), 7.20(m, 2H), 7.11(m, 1H), 6.95(d, 2H), 4.87(m, 2H), 4.65(m, 1H), 3.86(s, 3H), 3.25(m, 1H), 2.88~2.76 (m, 5H), 2.56(m, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 3H), 1.40(br, 1H), 1.05(m, 3H), 0.96(m, 3H)

[0202] Example 121: (S)-Quinuclidin-3-yl (6-(3-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.34(m, 2H), 7.27(m, 2H), 7.13(m, 1H), 6.86(m, 2H), 6.81(s, 1H), 4.87(m, 2H), 4.65(m, 1H), 3.84(s, 3H), 3.25(m, 1H), 2.88 ~2.76(m, 5H), 2.56(m, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 3H), 1.40(br, 1H), 1.05(m, 3H), 0.97(m, 3H)

[0203] Example 122: (S)-Quinuclidin-3-yl (6-(3-ethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.34~7.12(m, 3H), 7.09(m, 1H), 6.87(d, 1H), 6.84(d, 1H), 6.81(s, 1H), 4.87(m, 2H), 4.65(m, 1H), 4.01(m, 2H), 3.25(m, 1H), 2.88~2. 76(m, 5H), 2.56(m, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 3H), 1.40(br, 1H), 1.45(t, 3H), 1.05(m, 3H), 0.97(m, 3H)

[0204] Example 123: (S)-Quinuclidin-3-yl (6-(2-chloro-4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.34(m, 1H), 7.25(m, 1H), 7.08(m, 1H), 7.01(m, 2H), 6.87(d, 1H), 4.91(m, 1H), 4.87(m, 1H), 4.65(m, 1H), 3.87(s, 3H), 3.25(m, 1H) ), 2.88~2.76(m, 5H), 2.56(m, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 3H), 1.40(br, 1H), 1.03(m, 3H), 0.97(m, 3H)

[0205] Example 124: (S)-Quinuclidin-3-yl (6-(4-chloro-3-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.38(d, 1H), 7.28(m, 1H), 7.25(m, 1H), 7.10(m, 1H), 6.79(m, 2H), 4.91(m, 1H), 4.85(m, 1H), 4.66(m, 1H), 3.86(s, 3H), 3.25(m, 1H) ), 2.88~2.76(m, 5H), 2.56(m, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 3H), 1.40(br, 1H), 1.03(m, 3H), 0.97(m, 3H)

[0206] Example 125: (S)-Quinuclidin-3-yl (6-(2-chloro-5-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.37(m, 2H), 7.26(m, 1H), 7.03(m, 1H), 6.86(m, 1H), 6.74(m, 1H), 4.91(m, 1H), 4.85(m, 1H), 4.66(m, 1H), 3.81(s, 3H), 3.25(m, 1H) ), 2.88~2.76(m, 5H), 2.56(m, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 3H), 1.40(br, 1H), 1.03(m, 3H), 0.97(m, 3H)

[0207] Example 126: (S)-Quinuclidin-3-yl (6-(3-fluoro-4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.34~7.22(m, 2H), 7.04(m, 1H), 7.00(m, 3H), 4.91(m, 1H), 4.85(m, 1H), 4.66(m, 1H), 3.94(s, 3H), 3.25(m, 1H), 2.88~2. 76(m, 5H), 2.56(m, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 3H), 1.40(br, 1H), 1.03(m, 3H), 0.97(m, 3H)

[0208] Example 127: (S)-Quinuclidin-3-yl (6-(3-ethylphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.34(m, 1H), 7.26(m, 2H), 7.18(d, 1H), 7.10(m, 3H), 4.87(m, 1H), 4.77(m, 1H), 4.65(m, 1H), 3.25(m, 1H), 2.88~2.76(m, 5H), 2.67 (m, 2H), 2.58(m, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 2H), 1.40(br, 1H), 1.28(t, 3H), 1.04(m, 3H), 0.96(m, 3H)

[0209] Example 128: (S)-Quinuclidin-3-yl (6-(3-(tert-butyl)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.39~7.27(m, 5H), 7.14(m, 1H), 7.10(d, 1H), 4.87(m, 1H), 4.77(m, 1H), 4.65(m, 1H), 3.25(m, 1H), 2.88~2.76(m, 5H), 2. 58(m, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 2H), 1.40(br, 1H), 1.35(s, 9H), 1.06(m, 3H), 0.99(m, 3H)

[0210] Example 129: (S)-Quinuclidin-3-yl (6-(3-isopropylphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.35(m, 2H), 7.26(m, 2H), 7.20(m, 1H), 7.11(s, 1H), 7.08(m, 1H), 4.87(m, 1H), 4.77(m, 1H), 4.65(m, 1H), 3.25(m, 1H), 2.95(m, 1H), 2.88 ~2.76(m, 5H), 2.58(m, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 2H), 1.40(br, 1H), 1.28(d, 6H), 1.06(m, 3H), 0.99(m, 3H)

[0211] Example 130: (S)-Quinuclidin-3-yl (6-(3-(difluoromethyl)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.51(m, 2H), 7.42(m, 2H), 7.30(m, 1H), 7.25(m, 1H), 7.10(m, 2H), 6.84~6.55(t, 1H), 4.85(m, 1H), 4.77(m, 1H), 4.67(m, 1H), 3.25(m, 1H), 2.88~2.76(m, 5H), 2.58(m, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 2H), 1.40(br, 1H), 1.06(m, 3H), 0.99(m, 3H)

[0212] Example 131: (S)-Quinuclidin-3-yl (6-(3-(dimethylamino)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.30(m, 4H), 7.15(m, 1H), 6.73(m 1H), 6.63(m, 2H), 4.87(m, 1H), 4.77(m, 1H), 4.67(m, 1H), 3.25(m, 1H), 2.98(s, 6H), 2.88~2.76(m, 5H), 2. 58(m, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 2H), 1.40(br, 1H), 1.06(m, 3H), 0.99(m, 3H)

[0213] Example 132: (S)-Quinuclidin-3-yl (6-(3-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.30(m, 4H), 7.12(m, 1H), 6.87(m 1H), 6.79(m, 2H), 4.87(m, 1H), 4.77(m, 1H), 4.67(m, 1H), 4.57(m, 1H), 3.25(m, 1H), 2.88~2.76(m, 5H), 2.58(m, 2) H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 2H), 1.40(br, 1H), 1.36(d, 6H), 1.06(m, 3H), 0.99(m, 3H)

[0214] Example 133: (S)-Quinuclidin-3-yl (6-(2,3-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.30(m, 1H), 7.25(m, 1H), 7.11(m, 2H), 6.95(d, 1H), 6.74(m, 1H), 4.87(m, 1H), 4.77(m, 1H), 4.67(m, 1H), 3.92(s, 3H), 3.50(m, 3H), 3.25 (m, 1H), 2.88~2.76(m, 5H), 2.58(m, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 2H), 1.40(br, 1H), 1.06(m, 3H), 0.99(m, 3H)

[0215] Example 134: (S)-Quinuclidin-3-yl (6-(2,4-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.29(m, 1H), 7.25(m, 1H), 7.07(m, 1H), 7.01(m, 1H), 6.55(m, 2H), 4.87(m, 1H), 4.77(m, 1H), 4.67(m, 1H), 3.86(s, 3H), 3.73(m, 3H), 3.25 (m, 1H), 2.88~2.76(m, 5H), 2.58(m, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 2H), 1.40(br, 1H), 1.06(m, 3H), 0.99(m, 3H)

[0216] Example 135: (S)-Quinuclidin-3-yl (6-(2,5-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.27(m, 1H), 7.25(m, 1H), 7.08(m, 1H), 6.89(s, 2H), 6.70(d, 1H), 4.87(m, 1H), 4.77(m, 1H), 4.67(m, 1H), 3.79(s, 3H), 3.69(m, 3H), 3.25 (m, 1H), 2.88~2.76(m, 5H), 2.58(m, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 2H), 1.40(br, 1H), 1.06(m, 3H), 0.99(m, 3H)

[0217] Example 136: (S)-Quinuclidin-3-yl (6-(2,6-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.31(m, 3H), 7.03(m, 1H), 6.65(d, 2H), 4.87(m, 1H), 4.77(m, 1H), 4.67(m, 1H), 3.72(s, 6H), 3.25(m, 1H), 2.88~2.76 (m, 5H), 2.58(m, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 2H), 1.40(br, 1H), 1.03(m, 3H), 0.95(m, 3H)

[0218] Example 137: (S)-Quinuclidin-3-yl (6-(3,4-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.31(m, 2H), 7.11(m, 1H), 6.91(d, 1H), 6.79(m, 2H), 4.87(m, 1H), 4.77(m, 1H), 4.67(m, 1H), 3.93(s, 3H), 3.89(s, 3H), 3.25(m, 1H) ), 2.88~2.76(m, 5H), 2.58(m, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 2H), 1.40(br, 1H), 1.03(m, 3H), 0.95(m, 3H)

[0219] Example 138: (S)-Quinuclidin-3-yl (6-(3,5-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.34(m, 2H), 7.11(m, 1H), 6.46(s, 1H), 6.41(s, 2H), 4.87(m, 1H), 4.77(m, 1H), 4.67(m, 1H), 3.82(s, 6H), 3.25(m, 1H), 2.88 ~2.76(m, 5H), 2.58(m, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 2H), 1.40(br, 1H), 1.03(m, 3H), 0.95(m, 3H)

[0220] Example 139: (S)-Quinuclidin-3-yl (6-(3-chloro-4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.33~7.20(m, 3H), 7.14(d, 1H), 7.08(m, 1H), 6.97(d, 1H), 4.89(m, 1H), 4.77(m, 1H), 4.67(m, 1H), 3.94(s, 3H), 3.25(m, 1H), 2. 88~2.76(m, 5H), 2.57(m, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.61(br, 3H), 1.42(br, 1H), 1.03(m, 3H), 0.95(m, 3H)

[0221] Example 140: (S)-Quinuclidin-3-yl (6-(3-chloro-4-ethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.33~7.20(m, 3H), 7.11(d, 2H), 6.95(d, 1H), 4.87(m, 1H), 4.77(m, 1H), 4.65(m, 1H), 4.13(m, 2H), 3.25(m, 1H), 2.88~2.76(m, 5H), 2.5 8(m, 2H), 2.10(br, 1H), 1.93(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.61(br, 3H), 1.48(t, 3H), 1.42(br, 1H), 1.03(m, 3H), 0.95(m, 3H)

[0222] Example 141: (S)-Quinuclidin-3-yl (6-(3-chloro-4-propoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.31~7.21(m, 3H), 7.08(m, 2H), 6.95(d, 1H), 4.87(m, 1H), 4.77(m, 1H) ), 4.65(m, 1H), 4.02(m, 2H), 3.25(m, 1H), 2.88~2.76(m, 5H), 2.58(m, 2) H), 2.10(br, 1H), 1.93(br, 1H), 1.87(m, 2H), 1.85(br, 1H), 1.70(br, 1H), 1.61(br, 3H), 1.42(br, 1H), 1.10(t, 3H), 1.03(m, 3H), 0.95(m, 3H)

[0223] Example 142: (S)-Quinuclidin-3-yl (6-(3-fluoro-4-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.33~7.22(m, 2H), 7.08(m, 1H), 7.00(m, 2H), 6.97(m, 1H), 4.87(m, 1H), 4.77(m, 1H), 4.65(m, 1H), 4.57(m, 1H), 3.25(m, 1H), 2 .88~2.76(m, 5H), 2.58(m, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.61(br, 3H), 1.40(d, 6H), 1.03(m, 3H), 0.94(m, 3H)

[0224] Example 143: (S)-Quinuclidin-3-yl (6-(4-butoxy-3-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.31~7.22(m, 3H), 7.08(m, 2H), 6.97(d, 1H), 4.87(m, 1H), 4.77(m, 1H), 4.65(m, 1H), 4.06(m, 2H), 3.25(m, 1H), 2.88~2.76(m, 5H), 2.58(m, 2H), 2.10(br, 1H), 1.85(m, 3H), 1.70(br, 1H), 1.59(m, 5H), 1.40(br, 1H), 1.05(m, 3H), 1.03(t, 3H), 0.95(m, 3H)

[0225] Example 144: (S)-Quinuclidin-3-yl (6-(4-ethoxy-3-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.33~7.22(m, 2H), 7.08(m, 1H), 6.99(m, 3H), 4.87(m, 1H), 4.77(m, 1H), 4.65(m, 1H), 4.17(m, 2H), 3.25(m, 1H), 2.88~2.76(m, 5H), 2.58(m, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 3H), 1.48(t, 3H), 1.40(br, 1H), 1.04(m, 3H), 0.96(m, 3H)

[0226] Example 145: (S)-Quinuclidin-3-yl (6-(3-fluoro-4-propoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.33~7.22(m, 2H), 7.08(m, 1H), 6.99(m, 3H), 4.87(m, 1H), 4.77(m, 1H), 4.65(m, 1H), 4.05(m, 2H), 3.25(m, 1H), 2.88~2.76(m, 5H), 2. 58(m, 2H), 2.10(br, 1H), 1.88(m, 2H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 3H), 1.40(br, 1H), 1.08(t, 3H), 1.04(m, 3H), 0.96(m, 3H)

[0227] Example 146: (S)-Quinuclidin-3-yl (6-(3,5-dimethyl-4-propoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.28~7.20(m, 2H), 7.07(m, 1H), 6.89(s, 2H), 4.86(m, 1H), 4.78(m, 1H) ), 4.65(m, 1H), 3.78(m, 2H), 3.25(m, 1H), 2.88~2.76(m, 5H), 2.58(m, 2H), 2.31(s, 6H), 2.10(br, 1H), 1.88(m, 2H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 3H), 1.40(br, 1H), 1.12(t, 3H), 1.04(m, 3H), 0.96(m, 3H)

[0228] Example 147: (S)-Quinuclidin-3-yl (6-(4-butoxy-3,5-dimethylphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.28~7.20(m, 2H), 7.08(m, 1H), 6.89(s, 2H), 4.86(m, 1H), 4.78(m, 1H), 4.65(m, 1H), 3.80(m, 2H), 3.25(m, 1H), 2.88~2.76(m, 5H), 2 .58(m, 2H), 2.31(s, 6H), 2.10(br, 1H), 1.85(m, 3H), 1.70(br, 1H), 1.59(m, 5H), 1.40(br, 1H), 1.05(m, 3H), 1.01(t, 3H), 0.95(m, 3H)

[0229] Example 148: (S)-Quinuclidin-3-yl (6-(2-fluoro-4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.35(m, 1H), 7.25(m, 1H), 7.08(m, 2H), 6.77(d, 1H), 6.68(d, 1H), 4.86(m, 1H), 4.80(m, 1H), 4.68(m, 1H), 3.84(s, 3H), 3.25(m, 1H) , 2.88~2.76(m, 5H), 2.55(br, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 3H), 1.40(br, 1H), 1.05(m, 3H), 0.95(m, 3H)

[0230] Example 149: (S)-Quinuclidin-3-yl (6-(3-chloro-4-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.32~7.21(m, 3H), 7.07(m, 2H), 6.97(d, 1H), 4.89(m, 1H), 4.80(m, 1H), 4.68(m, 1H), 4.59(m, 1H), 3.25(m, 1H), 2.88~2 .76(m, 5H), 2.55(m, 2H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.59(m, 3H), 1.40(d, 7H), 1.03(m, 3H), 0.96(m, 3H)

[0231] Example 150: (S)-Quinuclidin-3-yl (6-(2-acetylthiophen-3-yl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.62(d, 1H), 7.37(m, 1H), 7.26(m, 1H), 7.09(m, 1H), 6.93(m, 1H), 4.80(m, 1H), 4.70(m, 1H), 4.67(m, 1H), 3.25(m, 1H), 2.88~2.76( m, 5H), 2.44(m, 2H), 2.10(br, 1H), 1.95(m, 3H), 1.85(br, 1H), 1.70(br, 1H), 1.61(br, 1H), 1.42(br, 1H), 1.01(m, 3H), 0.89(m, 3H)

[0232] Examples 151 to 170 The title compounds of Examples 151 to 170 were prepared according to the same procedure as in Example 1 using (S)-quinuclidin-3-yl (7-bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate prepared in Preparation Example 4; and the corresponding substituted boronic acids, respectively.

[0233] Example 151: (S)-Quinuclidin-3-yl (7-(4-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.53(m, 2H), 7.46(m, 1H), 7.38(m, 1H), 7.18(m, 1H), 7.11(m, 2H), 4.83(m, 2H), 4.68(m, 1H), 3.30(m, 1H), 2.99~2. 81(m, 7H), 2.14(m, 1H), 1.99(m, 1H), 1.89(m, 1H), 1.74(m, 2H), 1.64(m, 1H), 1.37(m, 1H), 1.12(m, 3H), 1.08(s, 3H)

[0234] Example 152: (S)-Quinuclidin-3-yl (7-(4-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.56(m, 1H), 7.48(m, 3H), 7.42(m, 2H), 7.20(d, 1H), 4.84(m, 2H), 4.66(m, 1H), 3.32(m, 1H), 2.98~2. 85(m, 7H), 2.12(m, 2H), 1.86(m, 1H), 1.72(m, 2H), 1.64(m, 1H), 1.51(m, 1H), 1.08(m, 3H), 0.99(s, 3H)

[0235] Example 153: (S)-Quinuclidin-3-yl (2,2-dimethyl-7-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.66(m, 4H), 7.51~7.42(m, 2H), 7.23(m, 1H), 4.85~4.81(m, 2H), 4.68(m, 1H), 3.29(m, 1H), 2.88~2.75(m, 7 H), 2.26(m, 1H), 2.09(m, 1H), 1.84(m, 1H), 1.73(m, 2H), 1.61(m, 1H), 1.43(m, 1H), 1.08(m, 3H), 0.99(s, 3H)

[0236] Example 154: (S)-Quinuclidin-3-yl (2,2-dimethyl-7-(4-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.71(m, 1H), 7.55(m, 2H), 7.48(m, 2H), 7.39(m, 1H), 7.19(m, 1H), 4.84(m, 2H), 4.68(m, 1H), 3.30(m, 1H), 2. 85(m, 7H), 2.23~2.14(m, 2H), 1.85(m, 1H), 1.72(m, 2H), 1.63(m, 1H), 1.44(m, 1H), 1.08(m, 3H), 0.99(s, 3H)

[0237] Example 155: (S)-Quinuclidin-3-yl (7-(3-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.71(m, 1H), 7.56(m, 1H), 7.45(m, 2H), 7.39(m, 1H), 7.26(m, 1H), 7.03(m, 1H), 4.87(m, 2H), 4.69(m, 1H), 3.31(m, 1) H), 2.87~2.73(m, 7H), 2.09(m, 2H), 1.84(m, 1H), 1.72(m, 2H), 1.61(br, 1H), 1.43(br, 1H), 1.09(m, 3H), 0.99(m, 3H)

[0238] Example 156: (S)-Quinuclidin-3-yl (7-(3-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.53~7.31(m, 6H), 7.20(m, 1H), 4.83(m, 2H), 4.68(m, 1H), 3.33(m, 1H), 2.88~2.81(m, 7H), 2 .09(m, 2H), 1.86(br, 1H), 1.72(m, 2H), 1.62(br, 1H), 1.46(br, 1H), 1.09(m, 3H), 0.99(m, 3H)

[0239] Example 157: (S)-Quinuclidin-3-yl (2,2-dimethyl-7-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.80(m, 2H), 7.56(m, 2H), 7.51(m, 1H), 7.43(m, 1H), 7.22(m, 1H), 4.87(m, 2H), 4.69(m, 1H), 3.30(m, 1H), 2.8 8~2.77(m, 7H), 2.13(m, 2H), 1.86(m, 1H), 1.73(m, 2H), 1.62(br, 1H), 1.42(br, 1H), 1.09(m, 3H), 0.99(m, 3H)

[0240] Example 158: (S)-Quinuclidin-3-yl (2,2-dimethyl-7-(3-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.48(m, 3H), 7.40(m, 2H), 7.21(m, 2H), 4.86(m, 2H), 4.71(m, 1H), 3.32(m, 1H), 2.92~2.86(m, 7H), 2.17 (br, 1H), 2.10(m, 2H), 1.90(m, 1H), 1.70(br, 1H), 1.66(br, 1H), 1.47(br, 1H), 1.09(m, 3H), 0.99(m, 3H)

[0241] Example 159: (S)-Quinuclidin-3-yl (7-(2-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.71(m, 1H), 7.47(m, 3H), 7.21(m, 2H), 7.16(m, 1H), 4.86(m, 2H), 4.69(m, 1H), 3.30(m, 1H), 2.89~2.81 (m, 7H), 2.13(m, 2H), 1.86(br, 1H), 1.72(m, 2H), 1.62(br, 1H), 1.45(br, 1H), 1.09(m, 3H), 1.00(m, 3H)

[0242] Example 160: (S)-Quinuclidin-3-yl (7-(2-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.71(m, 1H), 7.55(m, 2H), 7.31(m, 3H), 7.17(m, 1H), 4.85(m, 2H), 4.69(m, 1H), 3.30(m, 1H), 2.87~2.7 7(m, 7H), 2.19(m, 2H), 1.86(m, 1H), 1.72(m, 2H), 1.60(br, 1H), 1.41(br, 1H), 1.09(m, 3H), 1.00(m, 3H)

[0243] Example 161: (S)-Quinuclidin-3-yl (2,2-dimethyl-7-(2-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.74(m, 1H), 7.56(m, 1H), 7.48(m, 1H), 7.33(m, 1H), 7.26(m, 1H), 7.15(s, 2H), 4.82(m, 2H), 4.67(m, 1H), 3.29(m, 1H) ), 2.87~2.72(m, 7H), 2,20(m, 2H), 1.86(br, 1H), 1.72(m, 2H), 1.59(br, 1H), 1.43(br, 1H), 1.08(m, 3H), 0.99(m, 3H)

[0244] Example 162: (S)-Quinuclidin-3-yl (2,2-dimethyl-7-(2-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.69(m, 2H), 7.48(m, 4H), 7.18(m, 1H), 4.81(m, 2H), 4.68(m, 1H), 3.30(m, 1H), 2.87~2.77(m, 7H) ), 2.10(m, 2H), 1.86(br, 1H), 1.73(m, 2H), 1.61(br, 1H), 1.45(br, 1H), 1.08(m, 3H), 0.99(m, 3H)

[0245] Example 163: (S)-Quinuclidin-3-yl (2,2-dimethyl-7-(2-(p-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.93(m, 1H), 7.45(m, 2H), 7.21(m, 4H), 4.84(m, 2H), 4.68(m, 1H), 3.12(m, 1H), 2.98~2.84(m, 7H), 2.40(s, 3H) ), 2.16(m, 1H), 2.13(m, 1H), 1.93(br, 1H), 1.72(m, 2H), 1.63(br, 1H), 1.47(br, 1H), 1.07(m, 3H), 0.98(m, 3H)

[0246] Example 164: (S)-Quinuclidin-3-yl (7-(4-(difluoromethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.71(m, 2H), 7.55(m, 1H), 7.37(m, 1H), 7.20(s, 3H), 6.74~6.38(t, 1H), 4.84(m, 2H), 4.69(m, 1H), 3.21(m, 1H), 2 .91~2.81(m, 7H), 2.22(m, 2H), 1.89(br, 1H), 1.72(m, 2H), 1.64(br, 1H), 1.47(br, 1H), 1.08(m, 3H), 0.99(m, 3H)

[0247] Example 165: (S)-Quinuclidin-3-yl (7-(4-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.50(m, 3H), 7.40(m, 1H), 7.17(m, 1H), 7.09(m, 1H), 7.01(m, 1H), 4.90~4.80(m, 2H), 4.67(m, 1H), 4.18(s, 2H), 3.79(s, 2H), 3.48(s, 3H), 3.25(m, 1H), 2.91~2.76(m, 7H), 2.10(m, 2H), 1.88(br, 1H), 1.71(br, 2H), 1.60(br, 1H), 1.40(br, 1H), 1.08(m, 3H), 0.98(m, 3H)

[0248] Example 166: (S)-Quinuclidin-3-yl (7-(3-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.46(m, 1H), 7.41(m, 1H), 7.34(m, 1H), 7.18(m, 3H), 6.90(d, 1H), 4.90~4.80(m, 2H), 4.67(m, 1H), 4.18(s, 2H), 3.79(m, 2H), 3.48(m, 3H), 3.27(m, 1H), 2.86~2.72(m, 7H), 2.10(m, 2H), 1.88(br, 1H), 1.73(br, 2H), 1.60(br, 1H), 1.40(br, 1H), 1.07(m, 3H), 0.98(m, 3H)

[0249] Example 167: (S)-Quinuclidin-3-yl (7-(2-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.48(d, 1H), 7.41(d, 1H), 7.28(m, 2H), 7.12(m, 1H), 7.04(m, 2H), 4.98(d, 1H), 4.76(br, 1H), 4.67(d, 1H), 4.12(m, 2H), 3.70(m, 2H), 3.3 7(s, 3H), 3.26(m, 1H), 2.85~2.76(m, 7H), 2.10(m, 2H), 1.88(br, 1H), 1.73(br, 2H), 1.60(br, 1H), 1.40(br, 1H), 1.07(m, 3H), 0.98(m, 3H)

[0250] Example 168: (S)-Quinuclidin-3-yl (7-(4-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.48(m, 3H), 7.37(d, 1H), 7.16(d, 1H), 7.09(m, 2H), 5.22(s, 2H), 4.80(m, 2H), 4.67(d, 1H), 3.51(s, 3H), 3.27(m, 1H) ), 2.87~2.72(m, 7H), 2.22(m, 2H), 1.89(br, 1H), 1.72(m, 2H), 1.64(br, 1H), 1.47(br, 1H), 1.08(m, 3H), 0.99(m, 3H)

[0251] Example 169: (S)-Quinuclidin-3-yl (7-(3-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.49(m, 1H), 7.39(d, 1H), 7.33(m, 1H), 7.23~7.16(m, 3H), 7.02(d, 1H), 5.23(s, 2H), 4.81(m, 2H), 4.67(d, 1H), 3.51(s, 3H), 3 .27(m, 1H), 2.87~2.72(m, 7H), 2.22(m, 2H), 1.89(br, 1H), 1.72(m, 2H), 1.64(br, 1H), 1.47(br, 1H), 1.08(m, 3H), 0.99(m, 3H)

[0252] Example 170: (S)-Quinuclidin-3-yl (7-(2-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.55(m, 1H), 7.49(m, 1H), 7.37(m, 1H), 7.26(m, 2H), 7.20(m, 1H), 7.07(m, 1H), 5.13(m, 2H), 4.84(m, 2H), 4.69(m, 1H), 3.43(s, 3H) ), 3.25(m, 1H), 2.91~2.74(m, 7H), 2.22(m, 2H), 1.89(br, 1H), 1.72(m, 2H), 1.64(br, 1H), 1.47(br, 1H), 1.08(m, 3H), 0.99(m, 3H)

[0253] Examples 171 to 185 The title compounds of Examples 171 to 185 were prepared according to the same procedure as in Example 1 using (S)-quinuclidin-3-yl (7'-bromo-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate prepared in Preparation Example 6; and the corresponding substituted boronic acid, respectively.

[0254] Example 171: (S)-Quinuclidin-3-yl (7'-(4-fluorophenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.53(m, 3H), 7.40(d, 1H), 7.23(d, 1H), 7.13(m, 2H), 5.15(br, 1H), 4.76(br, 1H), 4.32(m, 1H), 3.26(m, 1H), 2.94~2.7 2(m, 7H), 2.13(m, 3H), 1.79(br, 1H), 1.67(br, 1H), 1.58(br, 1H), 1.38(br, 1H), 0.92(m, 1H), 0.58(m, 1H), 0.49(m, 2H)

[0255] Example 172: (S)-Quinuclidin-3-yl (7'-(4-chlorophenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.49(m, 2H), 7.41(m, 4H), 7.24(d, 1H), 5.17(br, 1H), 4.76(m, 1H), 4.33(m, 1H), 3.26(m, 1H), 2.91~2.73(m, 7H) ), 2.09(m, 3H), 1.79(br, 1H), 1.69(br, 1H), 1.59(br, 1H), 1.38(br, 1H), 0.92(m, 1H), 0.58(m, 1H), 0.49(m, 2H)

[0256] Example 173: (S)-Quinuclidin-3-yl (7'-(4-(trifluoromethyl)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.69(s, 4H), 7.56(d, 1H), 7.46(d, 1H), 7.25(m, 1H), 5.18(br, 1H), 4.77(m, 1H), 4.34(m, 1H), 3.27(m, 1H), 2.92~2.73 (m, 7H), 2.14(m, 3H), 1.79(br, 1H), 1.69(br, 1H), 1.58(br, 1H), 1.38(br, 1H), 0.92(m, 1H), 0.58(m, 1H), 0.50(m, 2H)

[0257] Example 174: (S)-Quinuclidin-3-yl (7'-(4-(trifluoromethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.58(m, 2H), 7.50(m, 1H), 7.43(d, 1H), 7.28(m, 3H), 5.17(br, 1H), 4.76(m, 1H), 4.33(m, 1H), 3.29(m, 1H), 2.90~2.78 (m, 7H), 2.13(m, 3H), 1.79(br, 1H), 1.69(br, 1H), 1.59(br, 1H), 1.39(br, 1H), 0.92(m, 1H), 0.58(m, 1H), 0.49(m, 2H)

[0258] Example 175: (S)-Quinuclidin-3-yl (7'-(3-fluorophenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.53(d, 1H), 7.44~7.35(m, 3H), 7.24(t, 2H), 7.04(t, 1H), 5.20(m, 1H), 4.77(m, 1H), 4.34(m, 1H), 3.27(m, 1H), 2.94~2.73( m, 7H), 2.06(m, 3H), 1.82(br, 1H), 1.70~1.67(br, 1H), 1.58(br, 1H), 1.41(br, 1H), 0.92(m, 1H), 0.58(br, 1H), 0.49(m, 2H)

[0259] Example 176: (S)-Quinuclidin-3-yl (7'-(3-chlorophenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.69(t, 1H), 7.55~7.41(m, 4H), 7.36(m, 1H), 7.23(d, 1H), 5.16(m, 1H), 4.77(m, 1H), 4.35(m, 1H), 3.26(m, 1H), 2.90~2. 73(m, 7H), 2.06(m, 3H), 1.79(br, 1H), 1.69(br, 1H), 1.59(br, 1H), 1.39(br, 1H), 0.93(m, 1H), 0.58(m, 1H), 0.49(m, 2H)

[0260] Example 177: (S)-Quinuclidin-3-yl (7'-(3-(trifluoromethyl)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.79(m, 2H), 7.55(m, 3H), 7.45(m, 1H), 7.27(m, 1H), 5.17(m, 1H), 4.77(m, 1H), 3.35(m, 1H), 3.26(m, 1H), 2.92~2.74(m, 7H) , 2.13(br, 1H), 2.08(m, 2H), 1.81(br, 1H), 1.69(br, 1H), 1.59(br, 1H), 1.39(br, 1H), 0.92(m, 1H), 0.59(m, 1H), 0.50(m, 2H)

[0261] Example 178: (S)-Quinuclidin-3-yl (7'-(3-(trifluoromethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.54~7.41(m, 5H), 7.26(m, 1H), 7.27(m, 1H), 5.16(m, 1H), 4.77(m, 1H), 4.35(m, 1H), 3.26(m, 1H), 2.94~2.74(m, 7H), 2. 18(br, 1H), 2.07(m, 2H), 1.80(br, 1H), 1.70(br, 1H), 1.59(br, 1H), 1.39(br, 1H), 0.93(m, 1H), 0.58(m, 1H), 0.50(m, 2H)

[0262] Example 179: (S)-Quinuclidin-3-yl (7'-(2-fluorophenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.49(m, 1H), 7.41(m, 2H), 7.32(m, 1H), 7.24(m, 2H), 7.15(m, 1H), 5.18(m, 1H), 4.76(m, 1H), 4.35(m, 1H), 3.27(m, 1H), 2.91~2.73 (m, 7H), 2.13(m, 1H), 2.08(d, 2H), 1.82(br, 1H), 1.69(br, 1H), 1.59(br, 1H), 1.43(br, 1H), 0.93(m, 1H), 0.60(m, 1H), 0.49(m, 2H)

[0263] Example 180: (S)-Quinuclidin-3-yl (7'-(2-chlorophenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.48(d, 1H), 7.41(d, 1H), 7.33(m, 4H), 7.22(m, 1H), 5.19(m, 1H), 4.74(m, 1H), 4.14(m, 1H), 3.23(m, 1H), 2.95~2.68 (m, 7H), 2.13(m, 3H), 1.80(br, 1H), 1.68(br, 1H), 1,57(br, 1H), 1.39(br, 1H), 0.90(m, 1H), 0.59(m, 1H), 0.49(m, 2H)

[0264] Example 181: (S)-Quinuclidin-3-yl (7'-(2-(trifluoromethyl)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.75(d, 1H), 7.56(m, 1H), 7.46(m, 1H), 7.33(m, 2H), 7.18(s, 2H), 5.14(m, 1H), 4.73(m, 1H), 4.32(m, 1H), 3.23(m, 1H), 2.9 5~2.69(m, 7H), 2.09(m, 3H), 1,81(br, 1H), 169(br, 1H), 1.56(br, 1H), 1.38(br, 1H), 0.89(m, 1H), 0.59(m, 1H), 0.49(m, 2H)

[0265] Example 182: (S)-Quinuclidin-3-yl (7'-(2-(trifluoromethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.43~7.31(m, 6H), 7.20(m, 1H), 5.15(m, 1H), 4.75(m, 1H), 4.33(m, 1H), 3.27(m, 1H), 2.95~2.63(m, 7H), 2. 09(m, 3H), 1.81(br, 1H), 1.69(br, 1H), 1.58(br, 1H), 1.39(br, 1H), 0.93(m, 1H), 0.57(m, 1H), 0.49(m, 2H)

[0266] Example 183: (S)-Quinuclidin-3-yl (7'-(p-tolyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.70(m, 1H), 7.57~7.46(m, 4H), 7.28~7.21(m, 2H), 5.15(m, 1H), 4.77(m, 1H), 4.34(m, 1H), 3.26(m, 1H), 2.90~2.68(m, 7H) , 2.40(s, 3H), 2.13(m, 3H), 1.81(br, 1H), 1.69(br, 1H), 1.59(br, 1H), 1.39(br, 1H), 0.94(m, 1H), 0.58(m, 1H), 0.48(m, 2H)

[0267] Example 184: (S)-Quinuclidin-3-yl (7'-(4-(difluoromethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.56(m, 3H), 7.42(m, 1H), 7.22(m, 3H), 6.74~6.37(t, 1H), 5.16(m, 1H), 4.76(m, 1H), 4.33(m, 1H), 3.26(m, 1H), 2.90~2. 67(m, 7H), 2.06(m, 3H), 1.75(br, 1H), 1.69(br, 1H), 1.59(br, 1H), 1.38(br, 1H), 0.92(m, 1H), 0.57(br, 1H), 0.49(m, 2H)

[0268] Example 185: (S)-Quinuclidin-3-yl (7'-(4-(methoxymethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.50(m, 3H), 7.40(d, 1H), 7.19(d, 1H), 7.11(m, 2H), 5.22(s, 2H), 5.13(m, 1H), 4.74(br, 1H), 4.33(d, 1H), 3.51(s, 3H), 3.25(m, 1H), 2.88~ 2.67(m, 7H), 2.05(br, 2H), 1.75(br, 1H), 1.68(br, 1H), 1.58(br, 1H), 1.37(br, 1H), 1.26(br, 1H), 0.93(m, 1H), 0.57(br, 1H), 0.47(m, 2H)

[0269] Examples 186 to 226 The title compounds of Examples 186 to 226 were prepared according to the same procedure as in Example 1 using (S)-quinuclidin-3-yl (6'-bromo-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate prepared in Preparation Example 5; and the corresponding substituted boronic acid, respectively.

[0270] Example 186: (S)-Quinuclidin-3-yl (6'-(4-fluorophenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.36(m, 1H), 7.32(m, 1H), 7.23(m, 2H), 7.13(d, 2H), 7.08(m, 1H), 5.13(m, 1H), 4.78(br, 1H), 4.31(d, 1H), 3.25(m, 1H), 2.85~2.76(m, 7H), 2.05(br, 1H), 1.95(br, 1H), 1.82(br, 1H), 1.69(br, 1H), 1.59(br, 1H), 1.35(br, 1H), 1.14(br, 1H), 0.89(m, 1H), 0.58(m, 1H), 0.45(m, 2H)

[0271] Example 187: (S)-Quinuclidin-3-yl (6'-(4-chlorophenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.37(d, 2H), 7.33(m, 1H), 7.25(m, 3H), 7.12(m, 1H), 5.13(m, 1H), 4.77(br, 1H), 4.34(d, 1H), 3.25(m, 1H), 2.85~2.76(m, 7H), 2.05( br, 1H), 1.95(br, 1H), 1.82(br, 1H), 1.69(br, 1H), 1.59(br, 1H), 1.35(br, 1H), 1.14(br, 1H), 0.89(m, 1H), 0.58(m, 1H), 0.45(m, 2H)

[0272] Example 188: (S)-Quinuclidin-3-yl (6'-(4-(trifluoromethyl)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.68(d, 2H), 7.40(d, 2H), 7.25(m, 2H), 7.12(m, 1H), 5.13(m, 1H), 4.77(br, 1H), 4.36(d, 1H), 3.25(m, 1H), 2.85~2.76(m, 7H), 2.05( br, 1H), 1.95(br, 1H), 1.82(br, 1H), 1.69(br, 1H), 1.59(br, 1H), 1.35(br, 1H), 1.14(br, 1H), 0.89(m, 1H), 0.58(m, 1H), 0.45(m, 2H)

[0273] Example 189: (S)-Quinuclidin-3-yl (6'-(4-(trifluoromethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.58(m, 1H), 7.35(d, 2H), 7.29~7.25(m, 3H), 7.12(m, 1H), 5.15(m, 1H), 4.77(br, 1H), 4.36(d, 1H), 3.25(m, 1H), 2.85~2.76(m, 7H), 2.0 5(br, 1H), 1.95(br, 1H), 1.82(br, 1H), 1.69(br, 1H), 1.59(br, 1H), 1.35(br, 1H), 1.14(br, 1H), 0.89(m, 1H), 0.58(m, 1H), 0.45(m, 2H)

[0274] Example 190: (S)-Quinuclidin-3-yl (6'-(3-fluorophenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1H-NMR (400MHz, CDCl 3 ) δ 7.39(m, 3H), 7.15(m, 1H), 7.09~7.01(m, 3H), 5.14(m, 1H), 4.78(br, 1H), 4.35(d, 1H), 3.25(m, 1H), 2.85~2.74(m, 7H), 2.05(br, 1H), 1.95(br, 1H), 1.82(br, 1H), 1.69(br, 1H), 1.59(br, 1H), 1.35(br, 1H), 1.14(br, 1H), 0.89(m, 1H), 0.56(m, 1H), 0.42(m, 2H)

[0275] Example 191: (S)-Quinuclidin-3-yl (6'-(3-chlorophenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.38~7.26(m, 5H), 7.19(m, 1H), 7.12(m, 1H), 5.14(m, 1H), 4.78(br, 1H), 4.36(d, 1H), 3.25(m, 1H), 2.85~2.74(m, 7H), 2.05(br, 1H), 1.95(br, 1H), 1.82(br, 1H), 1.69(br, 1H), 1.59(br, 1H), 1.35(br, 1H), 1.14(br, 1H), 0.89(m, 1H), 0.59(m, 1H), 0.46(m, 2H)

[0276] Example 192: (S)-Quinuclidin-3-yl (6'-(3-(trifluoromethyl)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.62(m, 1H), 7.56(m, 2H), 7.39(m, 1H), 7.29(m, 2H), 7.13(m, 1H), 5.14(m, 1H), 4.78(br, 1H), 4.36(d, 1H), 3.25(m, 1H), 2.85~2.74(m, 7H), 2.05(br, 1H), 1.95(br, 1H), 1.82(br, 1H), 1.69(br, 1H), 1.60(br, 1H), 1.35(br, 1H), 1.14(br, 1H), 0.89(m, 1H), 0.59(m, 1H), 0.48(m, 2H)

[0277] Example 193: (S)-Quinuclidin-3-yl (6'-(3-(trifluoromethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.50~7.26(m, 3H), 7.25~7.13(m, 4H), 5.14(m, 1H), 4.78(br, 1H), 4.35(d, 1H), 3.25(m, 1H), 2.85~2.74(m, 7H), 2.05(br, 1H) , 1.95(br, 1H), 1.82(br, 1H), 1.69(br, 1H), 1.60(br, 1H), 1.35(br, 1H), 1.14(br, 1H), 0.89(m, 1H), 0.59(m, 1H), 0.47(m, 2H)

[0278] Example 194: (S)-Quinuclidin-3-yl (6'-(4-(2-methoxyethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.32~7.25(m, 2H), 7.22(d, 2H), 7.15(m, 1H), 6.98(d, 2H), 5.12(m, 1H), 4.76 (br, 1H), 4.37(d, 1H), 4.18(d, 2H), 3.79(d, 2H), 3.48(s, 3H), 3.25(m, 1H), 2. 85~2.74(m, 7H), 2.05(br, 1H), 1.95(br, 1H), 1.82(br, 1H), 1.69(br, 1H), 1.5 9(br, 1H), 1.35(br, 1H), 1.10(br, 1H), 0.89(m, 1H), 0.56(m, 1H), 0.42(m, 2H)

[0279] Example 195: (S)-Quinuclidin-3-yl (6'-(3-(2-methoxyethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.35~7.25(m, 3H), 7.15(m, 1H), 6.93(d, 1H), 6.87(s, 2H), 5.14(m, 1H), 4.76 (br, 1H), 4.35(d, 1H), 4.15(d, 2H), 3.78(d, 2H), 3.47(s, 3H), 3.25(m, 1H), 2. 85~2.74(m, 7H), 2.05(br, 1H), 1.94(br, 1H), 1.80(br, 1H), 1.70(br, 1H), 1.5 9(br, 1H), 1.38(br, 1H), 1.14(br, 1H), 0.89(m, 1H), 0.58(m, 1H), 0.45(m, 2H)

[0280] Example 196: (S)-Quinuclidin-3-yl (6'-(2-(2-methoxyethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.35~7.25(m, 3H), 7.15(m, 1H), 7.05(m, 1H), 7.03(m, 1H), 6.97(d, 1H), 5.15(m, 1) H), 4.76(br, 1H), 4.33(m, 1H), 4.10(m, 2H), 3.61(m, 2H), 3.30~3.24(m, 3H), 3.25( m, 1H), 2.85~2.74(m, 7H), 2.05(br, 1H), 1.94(br, 1H), 1.80(br, 1H), 1.70(br, 1H) , 1.59(br, 1H), 1.38(br, 1H), 1.14(br, 1H), 0.89(m, 1H), 0.58(m, 1H), 0.45(m, 2H)

[0281] Example 197: (S)-Quinuclidin-3-yl (6'-(4-(methoxymethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.32~7.25(m, 2H), 7.22(d, 2H), 7.14(m, 1H), 7.08(d, 2H), 5.22(s, 2H), 5. 13(m, 1H), 4.77(br, 1H), 4.37(d, 1H), 3.53(s, 3H), 3.25(m, 1H), 2.85~2.6 7(m, 7H), 2.05(br, 1H), 1.95(br, 1H), 1.82(br, 1H), 1.69(br, 1H), 1.59(b r, 1H), 1.35(br, 1H), 1.10(br, 1H), 0.89(m, 1H), 0.56(m, 1H), 0.42(m, 2H)

[0282] Example 198: (S)-Quinuclidin-3-yl (6'-(3-(methoxymethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.35~7.25(m, 3H), 7.15(m, 1H), 6.93(d, 1H), 6.87(s, 2H), 5.20(s, 2H), 5. 13(m, 1H), 4.77(br, 1H), 4.37(d, 1H), 3.51(s, 3H), 3.25(m, 1H), 2.85~2.6 7(m, 7H), 2.05(br, 1H), 1.95(br, 1H), 1.82(br, 1H), 1.69(br, 1H), 1.59(b r, 1H), 1.35(br, 1H), 1.10(br, 1H), 0.89(m, 1H), 0.56(m, 1H), 0.42(m, 2H)

[0283] Example 199: (S)-Quinuclidin-3-yl (6'-(2-(methoxymethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.35~7.25(m, 3H), 7.15(m, 1H), 7.05(m, 1H), 7.03(m, 1H), 5.15(m, 1H), 5.10 ~5.07(m, 2H), 4.77(br, 1H), 4.36(d, 1H), 3.32~3.27(m, 3H), 3.25(m, 1H), 2.8 5~2.74(m, 7H), 2.05(br, 1H), 1.94(br, 1H), 1.80(br, 1H), 1.70(br, 1H), 1.5 9(br, 1H), 1.38(br, 1H), 1.14(br, 1H), 0.89(m, 1H), 0.58(m, 1H), 0.45(m, 2H)

[0284] Example 200: (S)-Quinuclidin-3-yl (6'-(2-chloro-4-methoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.38(m, 1H), 7.26(m, 1H), 7.14(m, 1H), 7.10(m, 1H), 7.04(m, 1H), 6.88(d, 1H), 5 .20~5.10(m, 1H), 4.75(m, 1H), 4.33(t, 1H), 3.85(s, 3H), 3.25(m, 1H), 2.85~2.7 3(m, 5H), 2.46(m, 2H), 2.05(br, 1H), 1.95(br, 1H), 1.82(br, 1H), 1.69(br, 1H), 1.59(br, 1H), 1.35(br, 1H), 1.10(br, 1H), 0.88(m, 1H), 0.56(m, 1H), 0.42(m, 2H)

[0285] Example 201: (S)-Quinuclidin-3-yl (6'-(4-chloro-3-methoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.39(d, 2H), 7.26(m, 1H), 7.13(m, 1H), 6.84(m, 2H), 5.14(m, 1H), 4.75(m, 1H), 4.35(d, 1H), 3.91(s, 3H), 3.25(m, 1H), 2.86~2.63(m, 7H), 2.00(m, 1H), 1.95(br, 1H), 1.75(br, 1H), 1.69(br, 1H), 1.59(br, 1H), 1.35(br, 1H), 1.10(br, 1H), 0.90(m, 1H), 0.58(m, 1H), 0.45(m, 2H)

[0286] Example 202: (S)-Quinuclidin-3-yl (6'-(3-fluoro-4-methoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.35(m, 1H), 7.26(m, 1H), 7.14(m, 1H), 7.06(m, 1H), 7.00(m, 2H), 5.15( m, 1H), 4.75(m, 1H), 4.36(d, 1H), 3.94(s, 3H), 3.25(m, 1H), 2.84~2.65(m , 7H), 2.06(br, 1H), 1.95(br, 1H), 1.82(br, 1H), 1.69(br, 1H), 1.59(br, 1H), 1.35(br, 1H), 1.10(br, 1H), 0.89(m, 1H), 0.56(m, 1H), 0.42(m, 2H)

[0287] Example 203: (S)-Quinuclidin-3-yl (6'-(3-ethylphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.35(m, 2H), 7.27(m, 1H), 7.17(m, 1H), 7.15(m, 3H), 5.15(m, 1H), 4.77( br, 1H), 4.34(d, 1H), 3.25(m, 1H), 2.87~2.71(m, 7H), 2.67(m, 2H), 2.10 (br, 1H), 1.92(br, 1H), 1.80(br, 1H), 1.68(br, 1H), 1.59(m, 1H), 1.40(br, 1H), 1.26(t, 3H), 1.10(m, 1H), 0.90(m, 1H), 0.59(m, 1H), 0.45(m, 2H)

[0288] Example 204: (S)-Quinuclidin-3-yl (6'-(3-(tert-butyl)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.40~7.33(m, 4H), 7.27(m, 1H), 7.18(m, 1H), 7.12(d, 1H), 5.15(m, 1H), 4.77(br, 1H), 4.38(d, 1H), 3.25(m, 1H), 2.87~2.66(m, 7H), 2.10(br , 1H), 1.92(br, 1H), 1.80(br, 1H), 1.68(br, 1H), 1.59(m, 1H), 1.40(br, 1H), 1.37(s, 9H), 1.10(m, 1H), 0.90(m, 1H), 0.59(m, 1H), 0.45(m, 2H)

[0289] Example 205: (S)-Quinuclidin-3-yl (6'-(3-isopropylphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.36(m, 2H), 7.27(m, 2H), 7.17(m, 2H), 7.13(d, 1H), 5.15(m, 1H), 4.77(br, 1H), 4.34(d, 1H), 3.25(m, 1H), 2.94(m, 1H), 2.87~2.71(m, 7H), 2.67(m, 2H) , 2.10(br, 1H), 1.92(br, 1H), 1.80(br, 1H), 1.68(br, 1H), 1.59(m, 1H), 1.4 0(br, 1H), 1.28(m, 6H), 1.10(m, 1H), 0.90(m, 1H), 0.59(m, 1H), 0.45(m, 2H)

[0290] Example 206: (S)-Quinuclidin-3-yl (6'-(3-(difluoromethyl)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.51(m, 2H), 7.43(m, 2H), 7.38(m, 1H), 7.27(m, 1H), 7.14(m, 1H), 6.84~6 .55(t, 1H), 5.15(m, 1H), 4.77(br, 1H), 4.34(d, 1H), 3.25(m, 1H), 2.86~2. 60(m, 7H), 2.10(br, 1H), 1.92(br, 1H), 1.80(br, 1H), 1.68(br, 1H), 1.59 (m, 1H), 1.40(br, 1H), 1.10(m, 1H), 0.90(m, 1H), 0.59(m, 1H), 0.45(m, 2H)

[0291] Example 207: (S)-Quinuclidin-3-yl (6'-(3-(dimethylamino)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.39~7.18(m, 4H), 6.74(d, 1H), 6.66(s, 2H), 5.15(m, 1H), 4.77(br, 1H), 4.34(d, 1H), 3.25(m, 1H), 2.97(s, 6H), 2.86~2.60(m, 7H), 2. 10(br, 1H), 1.92(br, 1H), 1.80(br, 1H), 1.68(br, 1H), 1.59(m, 1H), 1.40(br, 1H), 1.10(m, 1H), 0.88(m, 1H), 0.59(m, 1H), 0.44(m, 2H)

[0292] Example 208: (S)-Quinuclidin-3-yl (6'-(3-isopropoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.35~7.15(m, 3H), 7.15(m, 1H), 6.86(m, 3H), 5.15(m, 1H), 4.77(br, 1H) ), 4.57(m, 1H), 4.35(d, 1H), 3.25(m, 1H), 2.85~2.68(m, 7H), 2.08(br, 1H), 1.92(br, 1H), 1.80(br, 1H), 1.68(br, 1H), 1.59(br, 1H), 1.39(br, 1H), 1.35(d, 6H), 1.15(m, 1H), 0.88(m, 1H), 0.59(m, 1H), 0.44(m, 2H)

[0293] Example 209: (S)-Quinuclidin-3-yl (6'-(2,3-dimethoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.35(m, 1H), 7.24(m, 1H), 7.11(m, 2H), 6.96(d, 1H), 6.75(d, 1H), 5.16(m, 1) H), 4.77(br, 1H), 4.34(m, 1H), 3.92(s, 3H), 3.52(s, 3H), 3.25(m, 1H), 2.85 ~2.74(m, 7H), 2.08(br, 1H), 1.92(br, 1H), 1.80(br, 1H), 1.68(br, 1H), 1.5 9(br, 1H), 1.39(br, 1H), 1.15(m, 1H), 0.87(m, 1H), 0.56(m, 1H), 0.43(m, 2H)

[0294] Example 210: (S)-Quinuclidin-3-yl (6'-(2,4-dimethoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.31(m, 1H), 7.24(m, 1H), 7.11(m, 1H), 7.09(m, 1H), 6.56(d, 2H), 5.16(m, 1 H), 4.76(br, 1H), 4.34(d, 1H), 3.86(s, 3H), 3.75(s, 3H), 3.25(m, 1H), 2.85 ~2.74(m, 7H), 2.08(br, 1H), 1.92(br, 1H), 1.80(br, 1H), 1.68(br, 1H), 1.5 9(br, 1H), 1.39(br, 1H), 1.15(m, 1H), 0.89(m, 1H), 0.56(m, 1H), 0.43(m, 2H)

[0295] Example 211: (S)-Quinuclidin-3-yl (6'-(2,5-dimethoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.34(m, 1H), 7.24(m, 1H), 7.11(m, 1H), 6.88(m, 2H), 6.71(m, 1H), 5.16(m, 1) H), 4.76(br, 1H), 4.35(d, 1H), 3.79(s, 3H), 3.71(d, 3H), 3.25(m, 1H), 2.85 ~2.74(m, 7H), 2.08(br, 1H), 1.92(br, 1H), 1.80(br, 1H), 1.68(br, 1H), 1.5 9(br, 1H), 1.39(br, 1H), 1.15(m, 1H), 0.88(m, 1H), 0.56(m, 1H), 0.42(m, 2H)

[0296] Example 212: (S)-Quinuclidin-3-yl (6'-(2,6-dimethoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.32(m, 2H), 7.24(m, 1H), 7.06(d, 1H), 6.65(d, 2H), 5.16(m, 1H), 4.76(br, 1H), 4.35(d, 1H), 3.73(d, 6H), 3.25(m, 1H), 2.85~2.74(m, 7H) , 2.08(br, 1H), 1.92(br, 1H), 1.80(br, 1H), 1.68(br, 1H), 1.58(br, 1H), 1.39(br, 1H), 1.15(m, 1H), 0.89(m, 1H), 0.56(m, 1H), 0.40(m, 2H)

[0297] Example 213: (S)-Quinuclidin-3-yl (6'-(3,4-dimethoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.33(m, 1H), 7.24(m, 1H), 7.18(m, 1H), 6.92(d, 1H), 6.85(m, 2H), 5.14(m, 1) H), 4.77(br, 1H), 4.35(d, 1H), 3.93(s, 3H), 3.89(s, 3H), 3.25(m, 1H), 2.85 ~2.67(m, 7H), 2.08(br, 1H), 1.92(br, 1H), 1.80(br, 1H), 1.69(br, 1H), 1.5 8(br, 1H), 1.39(br, 1H), 1.15(m, 1H), 0.89(m, 1H), 0.58(m, 1H), 0.46(m, 2H)

[0298] Example 214: (S)-Quinuclidin-3-yl (6'-(3,5-dimethoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.34(m, 1H), 7.24(m, 1H), 7.17(m, 1H), 6.47(s, 1H), 6.44(d, 2H), 5.16( m, 1H), 4.76(br, 1H), 4.35(d, 1H), 3.82(s, 6H), 3.25(m, 1H), 2.85~2.67( m, 7H), 2.08(br, 1H), 1.92(br, 1H), 1.80(br, 1H), 1.69(br, 1H), 1.59(br, 1H), 1.39(br, 1H), 1.15(m, 1H), 0.89(m, 1H), 0.58(m, 1H), 0.45(m, 2H)

[0299] Example 215: (S)-Quinuclidin-3-yl (6'-(4-methoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.32(m, 1H), 7.22(m, 3H), 7.14(m, 1H), 6.96(m, 2H), 5.15(m, 1H), 4.77(br, 1H), 4.34(d, 1H), 3.86(s, 3H), 3.25(m, 1H), 2.87~2.71(m, 7H) , 2.10(br, 1H), 1.92(br, 1H), 1.80(br, 1H), 1.68(br, 1H), 1.59(m, 1H), 1.40(br, 1H), 1.10(m, 1H), 0.90(m, 1H), 0.59(m, 1H), 0.44(m, 2H)

[0300] Example 216: (S)-Quinuclidin-3-yl (6'-(3-methoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.34(t, 2H), 7.24(m, 1H), 7.17(m, 1H), 6.88(m, 2H), 6.84(s, 1H), 5.15( m, 1H), 4.77(br, 1H), 4.34(d, 1H), 3.86(s, 3H), 3.25(m, 1H), 2.87~2.71 (m, 7H), 2.10(br, 1H), 1.97(br, 1H), 1.80(br, 1H), 1.68(br, 1H), 1.59(m, 1H), 1.40(br, 1H), 1.10(m, 1H), 0.89(m, 1H), 0.59(m, 1H), 0.45(m, 2H)

[0301] Example 217: (S)-Quinuclidin-3-yl (6'-(4-ethoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.31(m, 1H), 7.25(m, 3H), 7.14(m, 1H), 6.94(d, 2H), 5.15(m, 1H), 4.77( br, 1H), 4.34(d, 1H), 4.07(m, 2H), 3.25(m, 1H), 2.87~2.71(m, 7H), 2.10 (br, 1H), 1.92(br, 1H), 1.80(br, 1H), 1.68(br, 1H), 1.59(m, 1H), 1.47(t, 3H), 1.40(br, 1H), 1.10(m, 1H), 0.90(m, 1H), 0.59(m, 1H), 0.44(m, 2H)

[0302] Example 218: (S)-Quinuclidin-3-yl (6'-(3-ethoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.33(m, 2H), 7.24(m, 1H), 7.15(m, 1H), 6.89(m, 2H), 6.83(s, 1H), 5.15(m, 1) H), 4.77(br, 1H), 4.35(d, 1H), 4.05(m, 2H), 3.25(m, 1H), 2.87~2.71(m, 7H) , 2.10(br, 1H), 1.98(br, 1H), 1.80(br, 1H), 1.68(br, 1H), 1.59(m, 1H), 1.4 5(t, 3H), 1.40(br, 1H), 1.10(m, 1H), 0.89(m, 1H), 0.59(m, 1H), 0.45(m, 2H)

[0303] Example 219: (S)-Quinuclidin-3-yl (6'-(4-isopropoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.32(m, 1H), 7.24(m, 1H), 7.21(d, 2H), 7.13(m, 1H), 6.93(d, 2H), 5.15(m, 1 H), 4.77(br, 1H), 4.57(m, 1H), 4.34(d, 1H), 3.25(m, 1H), 2.87~2.71(m, 7H) , 2.10(br, 1H), 1.92(br, 1H), 1.80(br, 1H), 1.68(br, 1H), 1.59(m, 1H), 1.4 0(br, 1H), 1.38(d, 6H), 1.15(m, 1H), 0.89(m, 1H), 0.58(m, 1H), 0.44(m, 2H)

[0304] Example 220: (S)-Quinuclidin-3-yl (6'-(4-propoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.33(m, 1H), 7.23(m, 3H), 7.15(m, 1H), 6.95(d, 2H), 5.15(m, 1H), 4.77(br, 1H), 4 .57(m, 1H), 4.34(d, 1H), 3.95(m, 2H), 3.25(m, 1H), 2.87~2.71(m, 7H), 2.10(br, 1H) ), 1.92(br, 1H), 1.85(m, 2H), 1.80(br, 1H), 1.68(br, 1H), 1.59(m, 1H), 1.40(br, 1H), 1.38(d, 6H), 1.15(m, 1H), 1.06(t, 3H), 0.88(m, 1H), 0.58(m, 1H), 0.44(m, 2H)

[0305] Example 221: (S)-Quinuclidin-3-yl (6'-(4-ethylphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.34(m, 1H), 7.26(m, 5H), 7.14(m, 1H), 5.15(m, 1H), 4.77(br, 1H), 4.57(m, 1H) ), 4.34(d, 1H), 3.25(m, 1H), 2.87~2.71(m, 7H), 2.67(m, 2H), 2.10(br, 1H), 1.9 2(br, 1H), 1.85(m, 2H), 1.80(br, 1H), 1.68(br, 1H), 1.59(m, 1H), 1.40(br, 1H) , 1.26(t, 3H), 1.15(m, 1H), 1.06(t, 3H), 0.88(m, 1H), 0.58(m, 1H), 0.44(m, 2H)

[0306] Example 222: (S)-Quinuclidin-3-yl (6'-(4-propylphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.34(m, 1H), 7.26(m, 5H), 7.14(m, 1H), 5.15(m, 1H), 4.77(br, 1H), 4.57(m, 1H) ), 4.34(d, 1H), 3.25(m, 1H), 2.87~2.71(m, 7H), 2.62(m, 2H), 2.10(br, 1H), 1.9 2(br, 1H), 1.80(br, 1H), 1.70(m, 2H), 1.68(br, 1H), 1.59(m, 1H), 1.40(br, 1H) , 1.26(t, 3H), 1.15(m, 1H), 1.01(t, 3H), 0.88(m, 1H), 0.58(m, 1H), 0.44(m, 2H)

[0307] Example 223: (S)-Quinuclidin-3-yl (6'-(4-isopropylphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.34(m, 1H), 7.26(m, 5H), 7.14(m, 1H), 5.15(m, 1H), 4.77(br, 1H), 4.57 (m, 1H), 4.34(d, 1H), 3.25(m, 1H), 2.96(m, 1H), 2.87~2.68(m, 7H), 2.10 (br, 1H), 1.92(br, 1H), 1.80(br, 1H), 1.68(br, 1H), 1.59(m, 1H), 1.40(br, 1H), 1.28(d, 6H), 1.15(m, 1H), 0.88(m, 1H), 0.58(m, 1H), 0.44(m, 2H)

[0308] Example 224: (S)-Quinuclidin-3-yl (6'-(4-isobutylphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.34(m, 1H), 7.27(m, 1H), 7.15(m, 5H), 5.15(m, 1H), 4.77(br, 1H), 4.57 (m, 1H), 4.34(d, 1H), 3.25(m, 1H), 2.87~2.68(m, 7H), 2.52(d, 2H), 2.10 (br, 1H), 1.92(m, 2H), 1.80(br, 1H), 1.68(br, 1H), 1.59(m, 1H), 1.40(br, 1H), 1.15(m, 1H), 0.92(d, 6H), 0.88(m, 1H), 0.58(m, 1H), 0.44(m, 2H)

[0309] Example 225: (S)-Quinuclidin-3-yl (6'-(4-(tert-butyl)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.44(d, 2H), 7.34(m, 1H), 7.23(m, 3H), 7.15(m, 1H), 5.15(m, 1H), 4.77(br, 1H), 4.57(m, 1H), 4.34(d, 1H), 3.25(m, 1H), 2.87~2.68(m, 7H), 2.10(br, 1H) ), 1.92(br, 1H), 1.80(br, 1H), 1.68(br, 1H), 1.59(m, 1H), 1.40(br, 1H), 1. 35(s, 9H), 1.15(m, 1H), 0.92(d, 6H), 0.88(m, 1H), 0.58(m, 1H), 0.44(m, 2H)

[0310] Example 226: (S)-Quinuclidin-3-yl (6'-(4-cyclopropylphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.34(m, 1H), 7.27(m, 1H), 7.19(m, 2H), 7.10(m, 3H), 5.15(m, 1H), 4.77(br, 1H), 4.36(d, 1H), 3.25(m, 1H), 2.85~2.68(m, 7H), 2.08(br, 1H), 1.92(br, 1 H), 1.80(br, 1H), 1.68(br, 1H), 1.59(br, 1H), 1.39(br, 1H), 1.35(d, 6H), 1 .15(m, 1H), 1.00(m, 2H), 0.88(m, 1H), 0.75(m, 2H), 0.59(m, 1H), 0.44(m, 2H)

[0311] Examples 227 to 232 The title compounds of Examples 227 to 232 were prepared according to the same procedure as in Example 1 using (S)-quinuclidin-3-yl (6-bromo-7-fluoro-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate prepared in Preparation Example 7; and the corresponding substituted boronic acids, respectively.

[0312] Example 227: (S)-Quinuclidin-3-yl (7-fluoro-6-(3-fluoro-4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.27(m, 2H), 7.10(d, 1H), 7.02(m, 2H), 4.92(m, 1H), 4.80(m, 1H), 4.61(d, 1H), 3.92(s, 3H), 3.27(m, 1H), 2.92~2.66( m, 7H), 2.08(br, 1H), 1.95(br, 1H), 1.82(m, 2H), 1.68(br, 1H), 1.60(br, 1H), 1.42(br, 1H), 1.05(m, 3H), 0.90(m, 3H)

[0313] Example 228: (S)-Quinuclidin-3-yl (6-(3,5-dimethyl-4-propoxyphenyl)-(7-fluoro-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.17(s, 2H), 7.12(d, 1H), 7.04(m, 1H), 4.88(m, 1H), 4.81(m, 1H), 4.63(d, 1H), 3.77(m, 2H), 3.27(m, 1H), 2.95~2.68(m, 7H) ), 2.35(s, 6H), 2.12(br, 1H), 1.93(m, 1H), 1.85(m, 2H), 1.71(m, 3H), 1.59(br, 1H), 1.43(br, 1H), 1.08(m, 6H), 0.95(m, 3H)

[0314] Example 229: (S)-Quinuclidin-3-yl (7-fluoro-2,2-dimethyl-6-(4-propylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.45(d, 2H), 7.24(m, 2H), 7.15(d, 1H), 7.06(m, 1H), 4.92(m, 1H), 4.81(m, 1H), 4.64(d, 1H), 3.27(m, 1H), 2.94~2.69 (m, 7H), 2.62(m, 2H), 2.14(br, 2H), 1.85(br, 1H), 1.70(m, 5H), 1.60(br, 1H), 1.42(br, 1H), 1.07(m, 3H), 0.99(m, 6H)

[0315] Example 230: (S)-Quinuclidin-3-yl (7-fluoro-6-(4-isobutylphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 7.42(d, 2H), 7.21(d, 2H), 7.16(d, 1H), 7.05(m, 1H), 4.91(m, 1H), 4.79(m, 1H), 4.66(d, 1H), 3.30(m, 1H), 2.95~2.72(m, 7H) , 2.53(d, 2H), 2.12(br, 2H), 1.90(m, 1H), 1.85(br, 1H), 1.71(m, 3H), 1.59(br, 1H), 1.43(br, 1H), 1.08(m, 3H), 0.93(m, 9H)

[0316] Example 231: (S)-Quinuclidin-3-yl (6-(2-(tert-butoxy)pyridin-4-yl)-(7-fluoro-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 8.14(d, 1H), 7.18(d, 1H), 7.09(m, 1H), 7.00(br, 1H), 6.82(s, 1H), 4.91(m, 1H), 4.79(m, 1H), 4.64(d, 1H), 3.28(m, 1H), 2.95 ~2.69(m, 7H), 2.11(br, 1H), 1.94(br, 1H), 1.84(br, 1H), 1.72(m, 3H), 1.60(br, 1H), 1.42(br, 1H), 1.07(m, 3H), 0.94(m, 3H)

[0317] Example 232: (S)-Quinuclidin-3-yl (7-fluoro-6-(4-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.45(d, 2H), 7.13(d, 1H), 7.05(m, 1H), 6.59(d, 2H), 4.91(m, 1H), 4.81(m, 1H), 4.64(m, 2H), 3.28(m, 1H), 2.97~2.69 (m, 7H), 2.12(br, 1H), 1.84(br, 1H), 1.71(m, 3H), 1.60(br, 1H), 1.43(br, 1H), 1.38(d, 6H), 1.07(m, 3H), 0.94(m, 3H)

[0318] Examples 233 to 238 The title compounds of Examples 233 to 238 were prepared according to the same procedure as in Example 1 using (S)-quinuclidin-3-yl (6-bromo-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate prepared in Preparation Example 8; and the corresponding substituted boronic acids, respectively.

[0319] Example 233: (S)-Quinuclidin-3-yl (6-(3-fluoro-4-methoxyphenyl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.31(m, 1H), 7.22(m, 1H), 6,99(m, 2H), 6.83(d, 1H), 4.90(m, 1H), 4.82(m, 1H), 4.61(d, 1H), 3.92(s, 3H), 3.77(d, 3H), 3.25 (m, 1H), 2.95~2.77(m, 7H), 2.09(br, 2H), 1.86(br, 2H), 1.67(br, 1H), 1.57(br, 1H), 1.41(br, 1H), 1.08(m, 3H), 0.99(m, 3H)

[0320] Example 234: (S)-Quinuclidin-3-yl (6-(3,5-dimethyl-4-propoxyphenyl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.12(s, 2H), 7.00(s, 1H), 6.84(d, 1H), 4.84(m, 1H), 4.81(m, 1H), 4.60(d, 1H), 3.75(m, 3H), 3.26(m, 1H), 2.89~2.76(m, 7H) ), 2.31(s, 6H), 2.08(br, 1H), 1.85(m, 3H), 1.68(m, 3H), 1.56(br, 1H), 1.40(br, 1H), 1.10(t, 3H), 1.05(m, 3H), 0.99(m, 3H)

[0321] Example 235: (S)-Quinuclidin-3-yl (7-methoxy-2,2-dimethyl-6-(4-propylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.42(d, 2H), 7.21(d, 2H), 7.03(s, 1H), 6.84(d, 1H), 4.83(m, 1H), 4.81(m, 1H), 4.63(d, 1H), 3.75(d, 3H), 3.27(m, 1H), 2.90 ~2.78(m, 7H), 2.63(m, 2H), 2.11(br, 2H), 1.85(br, 1H), 1.70(m, 5H), 1.60(br, 1H), 1.43(br, 1H), 1.06(m, 3H), 0.96(m, 6H)

[0322] Example 236: (S)-Quinuclidin-3-yl (6-(4-isobutylphenyl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.42(d, 2H), 7.15(d, 2H), 7.06(s, 1H), 6.86(d, 1H), 4.87(m, 1H), 4.73(m, 1H), 4.64(d, 1H), 3.78(d, 3H), 3.28(m, 1H), 2.89~2.79(m, 7H) , 2.51(d, 2H), 2.12(br, 2H), 1.90(m, 1H), 1.82(br, 1H), 1.68(m, 3H), 1.56(br, 1H), 1.42(br, 1H), 1.06(m, 3H), 0.99(m, 3H), 0.95(d, 6H)

[0323] Example 237: (S)-Quinuclidin-3-yl (6-(2-(tert-butoxy)pyridin-4-yl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3) δ 8.12(d, 1H), 7.07(s, 1H), 7.01(br, 1H), 6.88(d, 1H), 6.81(s, 1H), 4.82(m, 1H), 4.73(m, 1H), 4.62(d, 1H), 3.77(d, 3H), 3.27(m, 1H) ), 2.86~2.74(m, 7H), 2.11(br, 1H), 1.94(br, 1H), 1.84(br, 1H), 1.77(m, 3H), 1.60(s, 9H), 1.43(br, 1H), 1.08(m, 3H), 0.99(m, 3H)

[0324] Example 238: (S)-Quinuclidin-3-yl (6-(4-isopropoxyphenyl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 1 H-NMR (400MHz, CDCl 3 ) δ 7.42(d, 2H), 7.04(s, 1H), 6.92(d, 2H), 683(d, 1H), 4.86(m, 1H), 4.80(m, 1H), 4.70(m, 1H), 4.60(m, 1H), 3.79(d, 3H), 3.26(m, 1H) , 2.88~2.76(m, 7H), 2.12(br, 1H), 1.86(br, 1H), 1.68(m, 3H), 1.58(br, 1H), 1.42(br, 1H), 1.36(d, 6H), 1.05(m, 3H), 1.00(m, 3H)

[0325] Test Example 1: Evaluation of inhibitory activity against GCS The inhibitory activity of the compound of the present invention against GCS was evaluated according to the method described in a known literature (Hayashi Y et al., A sensitive and reproducible assay to measure the activity of glucosylceramide synthase and lactosylceramide synthase using HPLC and fluorescent substrates, Analytical Biochemistry 345 (2005) 181-186) as follows. Ibiglustat, known as a GCS inhibitor, was used as a control substance.

[0326] (1) Material A549 cells (ATCC, CCL-185) NBD C6-ceramide (Thermo Fisher, N1154) UDP-glucose (Sigma, U4625) Potassium chloride (Sigma, P9333) UltraPure TM 0.5M EDTA (Invitrogen, 15575-038) BCA Protein Assay Kit (Thermo Fisher, 23227) Iviglustat (Shanghai Systeam Biochem Co., Ltd., Genz-682452) HEPES (sigma, H3375) Protease / phosphatase inhibitor cocktail (CST, 5872s) DMEM (GIBCO, 11995-065) FBS (GIBCO, 16000-044) Antibiotic-Antimycotic(100X)(GIBCO, 15240-112) 200 mM L-glutamine (GIBCO, 25030081) PBS (GIBCO, 10010-023) 0.25% Trypsin-EDTA (GIBCO, 25200-056) Dimethyl sulfoxide (Sigma, 34869) 2-Propanol, HPLC grade (Burdick & Jackson, AH323-4) Hexane, HPLC grade (Burdick & Jackson, AH216-4) Chloroform (Sigma, C2432) Methanol (Merck, 1.06009.1011)

[0327] (2) Protocol <1> Preparation of cell lysates A549 cells (ATCC, CCL-185) were cultured in DMEM medium supplemented with 10% fetal bovine serum (FBS), 1x Antibiotic-Antimycotic, and 1x L-glutamine at 37°C and 5% CO 2 The cells were cultured in an incubator at 37 °C. After washing the cells attached to the culture dish with phosphate-buffered saline (PBS), the cells were scraped off with a cell scraper and centrifuged (4000 rpm, 3 min, 4 °C) to collect the cells in a 50 ml tube. The cell pellet was suspended in lysis buffer (50 mM HEPES, pH 7.3, containing 1x protease / phosphatase inhibitor cocktail) and lysed by sonication, after which the lysate was centrifuged (13000 rpm, 10 min, 4 °C). The resulting supernatant was used for quantitative analysis of protein. The amount of protein was measured using a BCA protein assay kit using bovine serum albumin as a standard.

[0328] <2> GCS Enzyme Reaction The enzyme reaction was initiated by sequentially adding the following reactants to a 96-deep-well plate, and then the enzyme reaction was carried out at 37°C for 90 min. [Table 1]

[0329] <3> lipid extraction The enzyme reaction was stopped by adding 100 μl of chloroform / methanol (2:1, v / v). After vortexing for 15 s, each mixture was centrifuged (4000 rpm, 10 min, 18°C). The lower layer (50 μl) was transferred to a new 96-deep-well plate and dried in a vacuum concentrator.

[0330] <4> HPLC analysis The lipids were dissolved in 100 μl of isopropyl alcohol / n-hexane / H 2 The sample (100 μl) was automatically loaded onto a normal phase column (Intersil SIL 150A-5, 4.6x250mm, GL Sciences, Japan) and diluted with isopropyl alcohol / n-hexane / H2O (55:44:1, v / v / v) and transferred to a glass vial for HPLC (Agilent, 8004-HP-H / i3u). 2 The solution was eluted with O (55:44:1, v / v / v) at a flow rate of 2.0 ml / min. The fluorescence was measured using a fluorescence detector (Agilent, 1260 FLD Spectra) with 470 nm and 530 nm as excitation and emission wavelengths, respectively.

[0331] <5> Data analysis Data analysis was performed according to the following formula. %Area(Sample) = Area(GlcCer) / [Area(Cer) + Area(GlcCer)] X 100 %GCS activity = [area(sample)-area(ibiglustat)] / [area(DMSO)-area(ibiglustat)] X 100 The obtained %GCS activity data was analyzed using the software GraphPad Prism (Ver 5.01) to obtain IC 50 The values ​​were calculated and the results are shown in Tables 1 and 2 below. [Table 2] TIFF0007636409000006.tif77165 [Table 3] TIFF0007636409000008.tif79165

[0332] The results in Tables 1 and 2 show that the compounds of the present invention exhibit excellent inhibitory activity against GCS.

[0333] Test Example 2: Evaluation of inhibitory activity against GM1 production GM1, the final product of sphingolipid metabolism, is expressed in the cell membrane and is therefore easy to detect. Furthermore, the amount of GM1 represents the conversion of ceramide to glucosylceramide. Therefore, the inhibitory activity of the compound of the present invention against GM1 production was evaluated according to the method described in the known literature (Dijkhuis et al., Gangliosides do not affect ABC transporter function in human neuroblastoma cells. The Journal of Lipid Research 47 (2006). 1187-1195) as follows. Ibiglustat, known as a GCS inhibitor, was used as a control substance.

[0334] (1) Material Jurkat cells, clone E6-1 (ATCC, TIB-152) Cholera toxin subunit B (CTB), FITC (Sigma, C1655) Iviglustat (Shanghai Systeam Biochem Co., Ltd., Genz-682452) DMSO (Sigma, D2650) Fixation buffer (BD, 554655) RPMI1640 (Gibco, A1049101) FBS (Gibco, 16000-044) Antibiotic-Antimycotic (100X) (Gibco, 15240-122) FACS sheath fluid (BD, 342003) Jurkat cells were cultured in RPMI1640 medium supplemented with 10% FBS and 1X Antibiotic-Antimycotic. Washing solution was prepared by adding 10 ml of FBS to 490 ml of FACS sheath fluid. CTB-FITC solution was prepared by diluting CTB-FITC stock solution (10 mg / ml) in washing solution to a final concentration of 2 μg / ml.

[0335] (2) Protocol Cell suspension (1X10 5 A total of 20,000 cells / ml was prepared in medium (RPMI 1640 medium supplemented with 10% FBS and 1X Antibiotic-Antimycotic). The cell suspension (200 μl) was added to each well of a 96-well plate (20,000 cells / well), and then treated with compounds at final concentrations of 0.05–3000 nM per well (3-fold, 11 points). Each mixture was incubated with CO 2 The plates were incubated at 37°C for 72 hours in an incubator. After centrifugation at 1500 rpm for 3 minutes to remove the medium, the cells were resuspended in 200 μl of washing solution per well. After centrifugation at 1500 rpm for 3 minutes to remove the washing solution, the cells were resuspended in 200 μl of 2 μg / ml CTB-FITC solution. The resulting suspension was incubated at 4°C for 60 minutes in the dark. After centrifugation at 1500 rpm for 3 minutes to remove the CTB-FITC solution, the cells were washed with 200 μl of washing solution. The washing process was repeated two more times. After centrifugation of the washed plate at 1500 rpm for 3 minutes to remove the washing solution, the cells were thoroughly resuspended in 200 μl of fixing buffer. IC 50 Guava TM Values ​​were determined by quantifying FITC fluorescence using easyCyte 5HT (Merck Millipore, 0500-4005).

[0336] Data analysis was performed according to the following formula. %MFI (median fluorescence intensity) = (fluorescence value of drug-treated group / fluorescence value of DMSO-treated group) × 100 % cells = (cell concentration in well / cell concentration in DMSO-treated group) x 100 The %MFI and %cell data were analyzed with the software GraphPad Prism (Ver 5.01) to obtain the IC 50 The values ​​were calculated and the results are shown in Tables 3 and 4 below. [Table 4] TIFF0007636409000010.tif78165 [Table 5] TIFF0007636409000012.tif79165

[0337] The results in Tables 3 and 4 show that the compounds of the present invention exhibit excellent inhibitory activity against GM1 production.

Claims

1. Chemical formula 1: 【Chemistry 1】 (In the formula, L is -O-; X is hydrogen; halogen; C １ ~C ６ Alkyl; C substituted with 1 to 3 halogens １ ~C ６ Alkyl; C １ ~C ６ Alkoxy; or C substituted with 1 to 3 halogens １ ~C ６ is an alkoxy; Y, Q and Z are each independently -CR ４ R ５ - and R ４ and R ５ are each independently hydrogen; halogen; １ ~C ６ Alkyl; C ３ ~C １０ Cycloalkyl; 3- to 12-membered heterocyclic group; or C １ ~C ６ Alkoxy or R ４ and R ５ together with the carbon atom of Y, Q or Z to which they are attached, ３ ~C １０ Forming a cycloalkyl, W is a bond; Ring A is a 6- to 12-membered aryl; a 5- to 12-membered heteroaryl; or a 3- to 12-membered heterocyclic group; X １ , X ２ , X ３ , and X ４ are each independently hydrogen; cyano; halogen; １ ~C ６ Alkyl; C substituted with 1 to 3 halogens １ ~C ６ Alkyl; C ３ ~C １０ Cycloalkyl; 3- to 12-membered heterocyclic group; C １ ~C ６ Alkoxy; C １ ~C ６ Alkoxy-C １ ~C ６ Alkoxy; C substituted with 1 to 3 halogens １ ~C ６ Alkoxy; C １ ~C ６ Alkylthio; morpholinyl; amino; mono- or di-C １ ~C ６ Alkylamino; C １ ~C ６ alkylcarbonyl; hydroxy; or nitro) or a pharma- ceutically acceptable salt thereof.

2. X is hydrogen, halogen, or C １ ~C ６ 2. The compound of claim 1, or a pharma- ceutically acceptable salt thereof, which is alkoxy.

3. R ４ and R ５ are each independently hydrogen or C １ ~C ６ alkyl or R ４ and R ５ together with the carbon atom of Y, Q or Z to which they are attached, ３ ~C １０ 2. The compound of claim 1, or a pharma- ceutically acceptable salt thereof, which is cycloalkyl.

4. Y is -CH ２ 2. The compound of claim 1, wherein:

5. Q is -CH ２ 2. The compound of claim 1, wherein:

6. Y is -CH ２ -; Q is -CH ２ -; Z is -CR ４ R ５ - and R ４ and R ５ are each independently hydrogen or C １ ~C ６ alkyl or R ４ and R ５ However, together with the carbon atom of Z, ３ ~C １０ 2. The compound of claim 1, or a pharma- ceutically acceptable salt thereof, which is cycloalkyl.

7. 2. The compound of claim 1, or a pharma- ceutically acceptable salt thereof, wherein the A ring is phenyl, benzodioxolyl, 2,3-dihydrobenzodioxinyl, 2,3-dihydrobenzofuranyl, pyridinyl, pyrrolo[2.3-b]pyridinyl, pyrimidinyl, or thienyl.

8. X １ , X ２ , X ３ , and X ４ are each independently hydrogen; cyano; halogen; １ ~C ６ Alkyl; C substituted with 1 to 3 halogens １ ~C ６ Alkyl; C ３ ~C １０ Cycloalkyl; C １ ~C ６ Alkoxy; C １ ~C ６ Alkoxy-C １ ~C ６ Alkoxy; C substituted with 1 to 3 halogens １ ~C ６ Alkoxy; morpholinyl; mono- or di-C １ ~C ６ alkylamino; or C １ ~C ６ 2. The compound of claim 1, or a pharma- ceutically acceptable salt thereof, which is alkylcarbonyl.

9. L is -O-; X is hydrogen, halogen, or C １ ~C ６ is an alkoxy; R ４ and R ５ are each independently hydrogen or C １ ~C ６ alkyl or R ４ and R ５ together with the carbon atom of Y, Q or Z to which they are attached, ３ ~C １０ Forming a cycloalkyl, W is a bond; the A ring is phenyl, benzodioxolyl, 2,3-dihydrobenzodioxinyl, 2,3-dihydrobenzofuranyl, pyridinyl, pyrrolo[2.3-b]pyridinyl, pyrimidinyl, or thienyl; X １ , X ２ , X ３ , and X ４ are each independently hydrogen; cyano; halogen; １ ~C ６ Alkyl; C substituted with 1 to 3 halogens １ ~C ６ Alkyl; C ３ ~C １０ Cycloalkyl; C １ ~C ６ Alkoxy; C １ ~C ６ Alkoxy-C １ ~C ６ Alkoxy; C substituted with 1 to 3 halogens １ ~C ６ Alkoxy; morpholinyl; mono- or di-C １ ~C ６ alkylamino; or C １ ~C ６ is alkylcarbonyl, 2. The compound of claim 1 or a pharma- ceutically acceptable salt thereof.

10. Y is -CH ２ 10. The compound of claim 9, wherein:

11. Q is -CH ２ 10. The compound of claim 9, wherein:

12. Y is -CH ２ -; Q is -CH ２ -; Z is -CR ４ R ５ - and R ４ and R ５ are each independently hydrogen or C １ ~C ６ alkyl or R ４ and R ５ However, together with the carbon atom of Z, ３ ~C １０ 10. The compound of claim 9, or a pharma- ceutically acceptable salt thereof, which is cycloalkyl.

13. (S)-Quinuclidin-3-yl (6-(4-fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-(difluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(p-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,4-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,5-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,5-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,4-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,3-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,3,4-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,4,5-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,5-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,5-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-(2-methoxyethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-(methoxymethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-(2-methoxyethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-(methoxymethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-(2-methoxyethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-(methoxymethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-ethylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-propylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-butylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-isopropylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-isobutylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-(tert-butyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-cyclopropyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-ethylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-(tert-butyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-isopropylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-ethylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,3-dihydrobenzofuran-6-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-morpholinophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-fluoropyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-methylpyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-methoxypyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(1H-pyrrolo[2,3-b]pyridin-5-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(pyrimidin-5-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(4-fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(4-chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(p-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(3-(fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(3-(chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(2-(fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(2-chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(2-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(3,4-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(2,4-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(2,4,5-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(2,5-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(3,5-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(2,3,4-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(2,5-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(pyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(pyridin-3-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(o-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(2-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(2-ethoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(3-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(2-isopropoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(4-(2-methoxyethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(4-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(4-ethoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(4-propoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(4-isopropoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(benzo[d]dioxol-5-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(m-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(4-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(3-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(2-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(2-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(p-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-(difluoromethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,4-difluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,4-difluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,3-difluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,5-difluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,5-difluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,5-dichlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,4-dichlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,5-dichlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(2,4,5-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(2,3,4-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-methoxypyridin-4-yl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(2-methylpyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-fluoropyridin-4-yl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(2-(trifluoromethyl)pyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-ethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-chloro-4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-chloro-3-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-chloro-5-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-fluoro-4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-ethylphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-(tert-butyl)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-isopropylphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-(difluoromethyl)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-(dimethylamino)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,3-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,4-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,5-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,6-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,4-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,5-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-chloro-4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-chloro-4-ethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-chloro-4-propoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-fluoro-4-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-butoxy-3-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-ethoxy-3-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-fluoro-4-propoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,5-dimethyl-4-propoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-butoxy-3,5-dimethylphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-fluoro-4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-chloro-4-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-acetylthiophen-3-yl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(4-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(4-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-7-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-7-(4-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(3-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(3-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-7-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-7-(3-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(2-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(2-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-7-(2-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-7-(2-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-7-(2-(p-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(4-(difluoromethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(4-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(3-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(2-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(4-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(3-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-(2-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7'-(4-fluorophenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (7'-(4-chlorophenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (7'-(4-(trifluoromethyl)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (7'-(4-(trifluoromethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (7'-(3-fluorophenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (7'-(3-chlorophenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (7'-(3-(trifluoromethyl)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (7'-(3-(trifluoromethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (7'-(2-fluorophenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (7'-(2-chlorophenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (7'-(2-(trifluoromethyl)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (7'-(2-(trifluoromethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (7'-(p-tolyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (7'-(4-(difluoromethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (7'-(4-(methoxymethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-fluorophenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-chlorophenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-(trifluoromethyl)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-(trifluoromethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3-fluorophenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3-chlorophenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3-(trifluoromethyl)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3-(trifluoromethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-(2-methoxyethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3-(2-methoxyethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(2-(2-methoxyethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-(methoxymethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3-(methoxymethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(2-(methoxymethoxy)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(2-chloro-4-methoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-chloro-3-methoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3-fluoro-4-methoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3-ethylphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3-(tert-butyl)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3-isopropylphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3-(difluoromethyl)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3-(dimethylamino)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3-isopropoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(2,3-dimethoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(2,4-dimethoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(2,5-dimethoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(2,6-dimethoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3,4-dimethoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3,5-dimethoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-methoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3-methoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-ethoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(3-ethoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-isopropoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-propoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-ethylphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-propylphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-isopropylphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-isobutylphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-(tert-butyl)phenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-cyclopropylphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (7-fluoro-6-(3-fluoro-4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,5-dimethyl-4-propoxyphenyl)-(7-fluoro-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-fluoro-2,2-dimethyl-6-(4-propylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-fluoro-6-(4-isobutylphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-(tert-butoxy)pyridin-4-yl)-(7-fluoro-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-fluoro-6-(4-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-fluoro-4-methoxyphenyl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,5-dimethyl-4-propoxyphenyl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (7-methoxy-2,2-dimethyl-6-(4-propylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-isobutylphenyl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-(tert-butoxy)pyridin-4-yl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; and (S)-Quinuclidin-3-yl (6-(4-isopropoxyphenyl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 2. The compound of claim 1 selected from the group consisting of: or a pharma- ceutically acceptable salt thereof.

14. (S)-quinuclidin-3-yl (6-(4-fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-ethylphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-isopropylphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-fluoro-4-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,5-dimethyl-4-propoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-fluoro-4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-chloro-4-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; (S)-Quinuclidin-3-yl (6'-(4-propoxyphenyl)-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-naphthalen]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (7-fluoro-2,2-dimethyl-6-(4-propylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate; and (S)-Quinuclidin-3-yl (7-fluoro-6-(4-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate 2. The compound of claim 1 selected from the group consisting of: or a pharma- ceutically acceptable salt thereof.

15. (S)-Quinuclidin-3-yl (6-(3-ethylphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate.

16. (S)-Quinuclidin-3-yl (6-(3-fluoro-4-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate.

17. (S)-Quinuclidin-3-yl (6-(2-fluoro-4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate.

18. (S)-Quinuclidin-3-yl (6-(3-chloro-4-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate.

19. (S)-Quinuclidin-3-yl (7-fluoro-6-(4-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate.

20. A pharmaceutical composition for inhibiting glucosylceramide synthase, comprising the compound according to any one of claims 1 to 19 or a pharma- ceutically acceptable salt thereof as an active ingredient.

21. 21. The pharmaceutical composition of claim 20 for preventing or treating Gaucher's disease, Fabry's disease, Tay-Sachs disease, or Parkinson's disease.

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