Novel derivatives having 2,3-dihydro-1h-indene or 2,3-dihydrobenzofuran moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same

Abstract

To provide a compound having an inhibitory activity against glucosylceramide synthase, a method for producing the same, a pharmaceutical composition containing the same, and uses thereof.SOLUTION: A novel compound having a 2,3-dihydro-1H-indene or 2,3-dihydrobenzofuran moiety represented by the following <chemical formula 1a> or pharmaceutically acceptable salt thereof has an inhibitory activity against glucosylceramide synthase (GCS), and therefore can be usefully applied for preventing or treating various diseases associated with GCS, such as Gaucher disease, Fabry disease, Tay-Sachs disease, and Parkinson's disease.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a novel compound having inhibitory activity against glucosylceramide synthase (GCS), that is, a derivative having a 2,3-dihydro-1H-indenyl group or a 2,3-dihydrobenzofuran group, or a pharmaceutically acceptable salt thereof, a method for producing the same, a pharmaceutical composition containing the same, and use thereof.

Background Art

[0002] Lysosomal storage disease (LSD) is a metabolic disorder caused by a genetic deficiency or lack of a specific enzyme in lysosomes. LSD shows various pathological symptoms throughout the body because unmetabolized or undegraded substrates accumulate. Currently, about 50 types of LSD are known, and depending on the accumulated substance, they are roughly classified into diseases such as mucopolysaccaridosis, oligosaccharidosis, and sphingolipidosis.

[0003] Among the diseases, sphingolipidosis, a type of glycolipid storage disorder related to sphingolipid metabolism, shows pathological conditions due to the accumulation of various membrane sphingoglycolipids (GSL) such as glucosylceramide and trihexosylceramide. For example, when enzymes related to sphingolipid metabolism such as beta-glucosidase and alpha-galactosidase do not have normal activity, their substrates (such as glucosylceramide, trihexosylceramide, etc.) accumulate, resulting in the appearance of various pathological conditions such as Gaucher's disease and Fabry's disease.

[0004] There are two known treatment methods for LSD. The first method is to replace or supplement the insufficient or deficient metabolic enzymes. Such enzyme replacement therapy (ERT) is safe and effective, but requires regular intravenous administration of the relevant enzyme; the dosage needs to be adjusted according to the enzyme reaction; and the cost is relatively high. In particular, since it is difficult to deliver the enzyme to the nervous system, ERT does not show sufficient effect in the treatment of symptoms related to the nervous system. Furthermore, there is also the problem that autoantibodies against the administered enzyme are frequently generated.

[0005] The second method is substrate reduction therapy (SRT) to inhibit the synthesis of the accumulating substrate. Glucosylceramide synthase (GCS) (also called "UDP-glucose:ceramide glucosyltransferase", "UDP-glucose:N-acylsphingosine D-glucosyltransferase", or "EC 2.4.1.80"), an enzyme involved in sphingolipid metabolism, is involved in the reaction of ceramide and 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 abnormal accumulation of glycolipids (such as trihexosylceramide, GM1, GM2) in cells and organs.

[0006] Thus, since GCS inhibitors inhibit the activity of GCS and prevent the accumulation of glycolipids, they can be usefully applied to 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, Krabbe disease, etc. GCS inhibitors can also be used for the treatment of secondary diseases associated with glycolipid storage such as Niemann-Pick disease (type C), mucopolysaccharidosis, and mucolipidosis type IV (see Chen CS, et al., Abnormal transport along the lysosomal pathway in mucolipidosis, type IV disease Proc Natl Acad Sci U S 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 U S A. 1991 Dec 15;88(24):11330-4). In addition, diseases associated with the accumulation of glycolipids such as renal hypertrophy (e.g., diabetic nephropathy); hyperglycemia or hyperinsulinemia; cancers associated with abnormal glycolipid synthesis; infectious diseases caused by organisms that use cell surface glycolipids as receptors; infectious diseases in which the synthesis of glucosylceramide is essential or important; diseases in which excessive glycolipid synthesis occurs (e.g., atherosclerosis, polycystic kidney, and renal hypertrophy); neuropathies and / or injuries associated with the recruitment and activation of macrophages (e.g., Alzheimer's disease, epilepsy, stroke, spinal cord diseases, Parkinson's disease, etc.); inflammatory diseases or disorders (e.g., rheumatoid arthritis, Crohn's disease, asthma, sepsis); and it has been reported to be useful for the treatment of diabetes and obesity (see WO2006 / 053043).Moreover, overexpression of GCS inhibits 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 the treatment of 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 PROBLEMS TO BE SOLVED BY THE INVENTION

[0008] The present inventors have found that derivatives having a 5,6-fused bicyclic group, i.e., a 2,3-dihydro-1H-indenyl group or a 2,3-dihydrobenzofuranyl group, or pharmaceutically acceptable salts thereof have excellent inhibitory activity against glucosylceramide synthase (GCS). Therefore, the derivatives having a 2,3-dihydro-1H-indenyl group or a 2,3-dihydrobenzofuranyl group, or pharmaceutically acceptable salts thereof can be usefully applied for preventing or treating various diseases related to GCS, such as Gaucher's disease, Fabry disease, Tay-Sachs disease, Parkinson's disease, etc.

[0009] Accordingly, the present invention provides derivatives having a 2,3-dihydro-1H-indenyl group or a 2,3-dihydrobenzofuranyl group, or pharmaceutically acceptable salts thereof, methods for producing these, pharmaceutical compositions containing these, and uses of these.

Means for Solving the Problem

[0010] According to one aspect of the present invention, there is provided a derivative having a 2,3-dihydro-1H-indenyl group or a 2,3-dihydrobenzofuran group, or a pharmaceutically acceptable salt thereof.

[0011] According to another aspect of the present invention, there is provided a method for producing a derivative having a 2,3-dihydro-1H-indenyl group or a 2,3-dihydrobenzofuran group, or a pharmaceutically acceptable salt thereof.

[0012] According to still another aspect of the present invention, there is provided a pharmaceutical composition comprising, as an active ingredient, a derivative having a 2,3-dihydro-1H-indenyl group or a 2,3-dihydrobenzofuran group, or a pharmaceutically acceptable salt thereof.

[0013] According to still another aspect of the present invention, there is provided a treatment method comprising administering a derivative having a 2,3-dihydro-1H-indenyl group or a 2,3-dihydrobenzofuran group, or a pharmaceutically acceptable salt thereof.

[0014] According to still another aspect of the present invention, there is provided the use of a derivative having a 2,3-dihydro-1H-indenyl group or a 2,3-dihydrobenzofuran group, or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for inhibiting glucosylceramide synthase.

Advantages of the Invention

[0015] According to the present invention, it has been found that a derivative having a 5,6-fused bicyclic group, namely, a 2,3-dihydro-1H-indenyl group or a 2,3-dihydrobenzofuranyl group, or a pharmaceutically acceptable salt thereof has excellent inhibitory activity against glucosylceramide synthase (GCS). Therefore, the compound according to the present invention or a pharmaceutically acceptable salt thereof can be usefully applied for preventing or treating various diseases related to GCS, such as Gaucher disease, Fabry disease, Tay-Sachs disease, Parkinson's disease and the like.

BEST MODE FOR CARRYING OUT THE INVENTION

[0016] As used herein, the term "alkyl" refers to a linear or branched aliphatic hydrocarbon group. For example, C1-C6 alkyl refers to a linear or branched 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 "-OH" group. The term "alkoxy" refers to a group formed by substituting the hydrogen atom of a hydroxyl group with an alkyl. For example, C1-C6 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 group, a bromo group, a chloro group, or an iodo group.

[0019] The term "cycloalkyl" refers to a saturated aliphatic 3- to 10-membered ring, preferably a 3- to 7-membered ring, unless otherwise specified. 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 with one hydrogen atom removed, including monocyclic or polycondensed ring systems such as 5- to 14-membered substituted or unsubstituted rings, and forms in which a plurality of aryls are linked by single bonds. "Aryl" includes, for example, phenyl, naphthyl, biphenyl, terphenyl, anthryl, indenyl, fluorenyl, phenanthryl, triphenylenyl, pyrenyl, perylenyl, chrysenyl, naphthacenyl, fluoranthenyl, etc., but is not limited thereto.

[0021] The term "heteroaryl" refers to a 5- to 12-membered aromatic group having 1 to 3 heteroatoms selected from the group consisting of a nitrogen atom (N), an oxygen atom (O), and a sulfur atom (S), and includes a 5- or 6-membered monocyclic heteroaryl group and a bicyclic heteroaryl group formed by condensation of a 5- or 6-membered monocyclic heteroaryl group with a benzene ring or a pyridine ring. The term "heterocyclic ring" refers to a 3- to 12-membered monocyclic ring or polycyclic ring having one or more, preferably 1 to 4, same or different heteroatoms selected from the group consisting of an oxygen atom (O), a nitrogen atom (N), and a sulfur atom (S), but not including an aromatic ring. Non-limiting examples of heteroaryl or heterocyclic ring 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, 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, diazaspiroundecane, etc.), hexahydropyrrolopyrrole, pyrrolopyrrole, pyrrolopyridine, imidazopyridazine, dihydrobenzodioxin, dihydrobenzofuran, etc., but are not limited thereto.

[0022] The term "amino" refers to the "-NH2" group. The term "alkylamino" refers to an amino group substituted with mono- or di-alkyl. For example, a C1-C6 alkylamino group includes an amino group substituted with a mono- or di-C1-C6 alkyl group.

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

[0024] The present invention relates to a derivative having a 5,6-fused bicyclic group, namely a 2,3-dihydro-1H-indenyl group or a 2,3-dihydrobenzofuranyl group, or a pharmaceutically acceptable salt thereof, namely, Chemical Formula 1:

Chemical formula

[0025] (In the formula, L is -O-, -CO-, -CR1R2-, or -NR3, Y and Z are each independently -CR1R2-; -NR3-; -O-; or -S-, R1 and R2 are each independently hydrogen; halogen; C1-C6 alkyl; C1-C6 alkyl having a nitrogen atom, an oxygen atom, or a sulfur atom; C3-C 10 cycloalkyl; a 3- to 12-membered heterocyclic group; or C1-C6 alkoxy, or R1 and R2 together with the carbon atom to which they are attached form C3-C 10 cycloalkyl, R3 is hydrogen; C1-C6 alkyl; C1-C6 alkyl having a nitrogen atom, an oxygen atom, or a sulfur atom; C3-C 10 cycloalkyl; a 3- to 12-membered heterocyclic group; or C1-C6 alkoxy, X is hydrogen; halogen; C1-C6 alkyl; C1-C6 alkyl substituted with 1 to 3 halogens; C1-C6 alkyl having a nitrogen atom, an oxygen atom, or a sulfur atom; C1-C6 alkoxy; or C1-C6 alkoxy substituted with 1 to 3 halogens, W is a bond, -CH2-, -O-, -NH-, -CH2CH2-, -CH=CH-, or -C≡C-, Ring A is a 6- to 12-membered aryl; a 5- to 12-membered heteroaryl; C3-C 10a cycloalkyl; or a 3- to 12-membered heterocyclic group, X1, X2, X3, and X4 are each independently hydrogen; cyano; halogen; C1-C6 alkyl; C1-C6 alkoxy-C1-C6 alkyl; C1-C6 alkyl substituted with 1 to 3 halogens; C3-C 10 cycloalkyl; a 3- to 12-membered heterocyclic group; C1-C6 alkoxy; C1-C6 alkoxy substituted with 1 to 3 halogens; C1-C6 alkoxy-C1-C6 alkoxy; morpholinyl-C1-C6 alkoxy; mono- or di-C1-C6 alkylamino-C1-C6 alkoxy; C3-C 10 cycloalkyl-C1-C6 alkoxy; C1-C6 alkylthio; amino; mono- or di-C1-C6 alkylamino; C1-C6 alkylcarbonyl; hydroxy; or nitro) There is provided a compound represented by the formula or a pharmaceutically acceptable salt thereof.

[0026] In the compound of Chemical Formula 1 according to the present invention or a pharmaceutically acceptable salt thereof, L may be -O-.

[0027] In the compound of Chemical Formula 1 according to the present invention or a pharmaceutically acceptable salt thereof, Y and Z may each independently be -O- or -CR1R2-.

[0028] In the compound of Chemical Formula 1 according to the present invention or a pharmaceutically acceptable salt thereof, R1 and R2 are each independently hydrogen or C1-C6 alkyl, or R1 and R2 together with the carbon atom to which they are attached form a C3-C 10 cycloalkyl which may be formed. In one embodiment, Y may be -O-, and Z may be -CR1R2-.

[0029] In the compound of Chemical Formula 1 according to the present invention or a pharmaceutically acceptable salt thereof, X may be hydrogen, halogen, or C1-C6 alkoxy.

[0030] In the compound of Formula 1 or a pharmaceutically acceptable salt thereof according to the present invention, W may be a bond (i.e., the A ring is directly bonded to a 2,3-dihydro-1H-indenyl group or a 2,3-dihydrobenzofuranyl group) or -CH=CH-.

[0031] In the compound of Formula 1 or a pharmaceutically acceptable salt thereof according to the present invention, the A ring may be a 6- to 12-membered aryl; a 5- to 12-membered heteroaryl; or a 3- to 12-membered heterocyclic group. In one embodiment, the 6- to 12-membered aryl may be phenyl, naphthalenyl, or biphenyl. In another embodiment, the 5- to 12-membered heteroaryl may be benzodioxolyl, pyridinyl, thienyl, quinolinyl, isoquinolinyl, benzofuranyl, benzo[b]thienyl, quinoxalinyl, or furanyl. In yet another embodiment, the 3- to 12-membered heterocyclic group may be 2,3-dihydrobenzodioxinyl, 2,3-dihydrobenzofuranyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, chromanyl, or 3,4-dihydro-2H-benzo[b][1,4]dioxepinyl.

[0032] In the compound of Formula 1 or a pharmaceutically acceptable salt thereof according to the present invention, X1, X2, X3, and X4 are each independently hydrogen; cyano; halogen; C1-C6 alkyl; C1-C6 alkoxy-C1-C6 alkyl; C1-C6 alkyl substituted with 1 to 3 halogens; C3-C 10 cycloalkyl; morpholinyl; C1-C6 alkoxy; C1-C6 alkoxy substituted with 1 to 3 halogens; C1-C6 alkoxy-C1-C6 alkoxy; morpholinyl-C1-C6 alkoxy; mono- or di-C1-C6 alkylamino-C1-C6 alkoxy; C3-C 10 cycloalkyl-C1-C6 alkoxy; C1-C6 alkylthio; mono- or di-C1-C6 alkylamino; or C1-C6 alkylcarbonyl.

[0033] In a preferred embodiment of the present invention, L is -O- and Y and Z are each independently -O- or -CR1R2-, R1 and R2 are each independently hydrogen or C1-C6 alkyl, or R1 and R2 together with the carbon atom to which they are attached form a C3-C 10 cycloalkyl, X is hydrogen, halogen, or C1-C6 alkoxy, W is a bond or -CH=CH-, Ring A is a 6- to 12-membered aryl; a 5- to 12-membered heteroaryl; or a 3- to 12-membered heterocyclic group, X1, X2, X3, and X4 are each independently hydrogen; cyano; halogen; C1-C6 alkyl; C1-C6 alkoxy-C1-C6 alkyl; C1-C6 alkyl substituted with 1 to 3 halogens; C3-C 10 cycloalkyl; morpholinyl; C1-C6 alkoxy; C1-C6 alkoxy substituted with 1 to 3 halogens; C1-C6 alkoxy-C1-C6 alkoxy; morpholinyl-C1-C6 alkoxy; mono- or di-C1-C6 alkylamino-C1-C6 alkoxy; C3-C 10 cycloalkyl-C1-C6 alkoxy; C1-C6 alkylthio; mono- or di-C1-C6 alkylamino; or C1-C6 alkylcarbonyl.

[0034] In the above embodiment, Y may be -O-, and Z may be -CR1R2-.

[0035] In the above embodiment, Ring A may be phenyl, naphthalenyl, or biphenyl.

[0036] In the above embodiment, Ring A may be benzodioxolyl, pyridinyl, thienyl, quinolinyl, isoquinolinyl, benzofuranyl, benzo[b]thienyl, quinoxalinyl, or furanyl.

[0037] In the above embodiment, ring A may be 2,3-dihydrobenzodioxinyl, 2,3-dihydrobenzofuranyl, 3,4-dihydro-2H-benzo[b][1,4]oxazinyl, chromanyl, or 3,4-dihydro-2H-benzo[b][1,4]dioxepinyl.

[0038] In the compound of Formula 1 or a pharmaceutically acceptable salt thereof, preferred compounds include compounds (including their pharmaceutically acceptable salts) selected from the group consisting of: (S)-Quinuclidin-3-yl (5-(4-fluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-chlorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-(trifluoromethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-fluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-chlorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-(trifluoromethyl)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-(trifluoromethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-fluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-chlorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-(trifluoromethyl)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-(trifluoromethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(p-tolyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-(difluoromethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3,4-difluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,4-difluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,3-difluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,5-difluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3,5-difluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,3,4-trifluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,4,5-trifluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3,5-dichlorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3,4-dichlorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,5-dichlorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-fluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-chlorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-(trifluoromethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-fluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-chlorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-(trifluoromethyl)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-(trifluoromethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-fluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-chlorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-(trifluoromethyl)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-(trifluoromethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-(difluoromethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(p-tolyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,4-difluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,5-difluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,5-difluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,3-difluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,4-difluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,4,5-trifluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,3,4-trifluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,5-dichlorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,4-dichlorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,5-dichlorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-fluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-chlorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(4-(trifluoromethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-fluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-chlorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(3-(trifluoromethyl)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(3-(trifluoromethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-fluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2-chlorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(2-(trifluoromethyl)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(p-tolyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-(difluoromethoxy)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,4-difluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,4-difluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,3-difluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,5-difluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,5-difluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(2,3,4-trifluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-(2,4,5-trifluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,5-dichlorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3,4-dichlorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(2,5-dichlorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(4-(2-methoxyethoxy)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-fluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-chlorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(4-(trifluoromethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-fluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-chlorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(3-(trifluoromethyl)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(3-(trifluoromethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-fluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-chlorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(2-(trifluoromethyl)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(2-(trifluoromethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(p-tolyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-(difluoromethoxy)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3,4-difluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,5-difluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,4-difluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3,5-difluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,3-difluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3,4-dichlorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,5-dichlorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3,5-dichlorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(2,3,4-trifluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(2,4,5-trifluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-(2-methoxyethoxy)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-(2-methoxyethoxy)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-(2-methoxyethoxy)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-(methoxymethoxy)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-(methoxymethoxy)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-(methoxymethoxy)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-ethoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-isopropoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-(dimethylamino)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(3-(methylthio)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-ethylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-isopropylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-(tert-butyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,3-dihydrobenzofuran-5-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(3-(2-morpholinoethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-(2-fluoroethoxy)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(4-(2,2,2-trifluoroethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(4-(2-morpholinoethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(2-(trifluoromethyl)pyridin-4-yl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,5-dichloropyridin-4-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-chloro-5-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-chloro-4-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-chloro-4-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-chloro-3-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-chloro-3-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,3-dichloro-4-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-chloro-4-isopropoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-fluoro-4-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-(dimethylamino)-4-fluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(chroman-6-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-cyclopropylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-(dimethylamino)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-ethoxy-3-fluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-methoxy-3-(trifluoromethyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(4-propoxyphenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-isobutoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(thiophen-3-yl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(4-methylthiophen-3-yl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-(2-(dimethylamino)ethoxy)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(isoquinolin-8-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(isoquinolin-5-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(isoquinolin-4-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(quinolin-3-yl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-isopropoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-isopropoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-(tert-butyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-ethylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(4-morpholinophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-(methoxymethyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-(2,2-difluoroethoxy)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(3-methyl-4-morpholinophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-fluoro-4-morpholinophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-chloro-4-morpholinophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3,4-dihydro-2H-benzo[b][1,4]dioxepin-7-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-(difluoromethyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(quinolin-8-yl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(benzofuran-3-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(benzofuran-2-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-ethoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-isobutylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,4-dichloro-3-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(4-propylphenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-butylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,3-dimethoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,4-dimethoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,5-dimethoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,6-dimethoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3,5-dimethoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-ethoxy-3-(trifluoromethyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,5-difluoro-4-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-fluoro-5-isopropoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3,5-dimethyl-4-propoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-ethoxy-3,5-dimethylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-ethylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-ethoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-chloro-5-(trifluoromethoxy)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-fluoro-2-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-methoxy-2-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-(tert-butoxymethyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-chloro-3-(trifluoromethyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-chloro-4-(trifluoromethyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,6-dimethoxypyridin-3-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(6-(cyclopropylmethoxy)pyridin-3-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(benzo[b]thiophen-2-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-(tert-butoxy)pyridin-4-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(6-methoxy-5-(trifluoromethyl)pyridin-3-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(6-methoxynaphthalen-2-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-([1,1'-biphenyl]-3-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(quinoxalin-6-yl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3,5-dimethylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(furan-2-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-isopropoxy-3,5-dimethylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-methoxy-3,5-dimethylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(6-isopropoxypyridin-3-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-(2-fluoroethoxy)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-ethoxy-5-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(3-propoxyphenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-methoxy-5-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-butoxy-5-fluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-butoxy-3-chlorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,4-dipropoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-chloro-4-ethoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-isobutoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-ethoxy-2-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-chloro-4-propoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(5-fluoro-2-isopropoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-fluoro-4-isopropoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(5-chloro-2-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-fluoro-5-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(5-chloro-2-ethoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(5-fluoro-2-propoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-fluoro-6-propoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-fluoro-4-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-fluoro-4-propoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(5-chloro-2-isopropoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-butoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-fluoro-5-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(5-fluoro-2-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-chloro-5-(trifluoromethyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-fluoro-5-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-chloro-5-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-methoxy-5-(trifluoromethyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-chloro-4-fluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-fluoro-3-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3,4-dimethylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-fluoro-2-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-fluoro-4-(trifluoromethyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-fluoro-5-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-fluoro-3-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(5-isopropyl-2-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-fluoro-4-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(5-fluoro-2-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(5-methylfuran-3-yl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-fluoro-2-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-chloro-3-fluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(benzo[b]thiophen-3-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-fluoro-2-propoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-(tert-butyl)-5-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-chloro-5-ethoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-chloro-3-fluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-fluoro-3-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(5-cyano-2-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-ethoxy-5-(trifluoromethyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-fluoro-5-(trifluoromethyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(3-methyl-4-(trifluoromethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(3-(methylthio)-5-(trifluoromethyl)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-fluoro-4-(trifluoromethoxy)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-ethoxy-4-(trifluoromethyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-methoxy-5-(trifluoromethyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,4-bis(trifluoromethyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-chloro-2-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-methoxy-4-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-fluoro-3-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-ethoxy-5-fluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-fluoro-5-propoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3,5-bis(trifluoromethyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-chloro-4-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,5-dimethylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-chloro-4-fluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(6-ethoxypyridin-3-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-ethoxypyridin-4-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-isopropoxypyridin-4-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(6-propoxypyridin-3-yl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(6-butoxypyridin-3-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(6-(2-methoxyethoxy)pyridin-3-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(6-isobutoxypyridin-3-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-isobutylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-butoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,4-dimethoxypyridin-3-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-acetylthiophen-3-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-((E)-3-fluorostyryl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-((E)-4-ethylstyryl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-((E)-2-cyclohexylvinyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-diethyl-5-(4-fluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-diethyl-5-(4-ethylphenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-diethyl-5-(4-propylphenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-(tert-butyl)phenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-butylphenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-cyclopropylphenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-diethyl-5-(4-isopropylphenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-diethyl-5-(4-methoxyphenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-ethoxyphenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-diethyl-5-(4-propoxyphenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-diethyl-5-(4-isopropoxyphenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-diethyl-5-(4-isobutylphenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-diethyl-5-(3-fluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-diethyl-5-(3-methoxyphenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-ethoxyphenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-diethyl-5-(3-isopropoxyphenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-diethyl-5-(3-ethylphenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-diethyl-5-(3-isopropylphenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-(tert-butyl)phenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,3-dimethoxyphenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,4-dimethoxyphenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,5-dimethoxyphenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3,4-dimethoxyphenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3,5-dimethoxyphenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,6-dimethoxyphenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-(difluoromethyl)phenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-(dimethylamino)phenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-ethoxy-3,5-dimethylphenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3,5-dimethyl-4-propoxyphenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-butoxy-3,5-dimethylphenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-diethyl-5-(thiophen-3-yl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-diethyl-5-(furan-3-yl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(6-(cyclopropylmethoxy)pyridin-3-yl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-diethyl-5-(2-fluoro-4-methoxyphenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-chloro-4-isopropoxyphenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-ethylphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-methoxy-2,2-dimethyl-5-(4-propylphenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-isopropylphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-isobutylphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-(tert-butyl)phenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-cyclopropylphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-ethoxyphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-methoxy-2,2-dimethyl-5-(4-propoxyphenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-isopropoxyphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3,5-dimethyl-4-propoxyphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-chloro-4-isopropoxyphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-fluoro-4-methoxyphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-butoxyphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-isobutylphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(6-(cyclopropylmethoxy)pyridin-3-yl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(5-chloro-2-methoxyphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-butylphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-methoxy-5-(4-methoxy-3,5-dimethylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-ethoxy-3,5-dimethylphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-butoxyl-3,5-dimethylphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate; (S)-Quinuclidin-3-yl (6-methoxy-5-(2-methoxypyridin-4-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate; (S)-Quinuclidin-3-yl (5-(3-fluorophenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate; (S)-Quinuclidin-3-yl (5-(3-ethylphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate; (S)-Quinuclidin-3-yl (5-(3-isobutylphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate; (S)-Quinuclidin-3-yl (5-(3-isopropylphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate; (S)-Quinuclidin-3-yl (5-(3-(tert-butyl)phenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate; (S)-Quinuclidin-3-yl (6-methoxy-5-(3-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate; (S)-Quinuclidin-3-yl (5-(3-ethoxyphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate; (S)-Quinuclidin-3-yl (6-methoxy-2,2-dimethyl-5-(3-propoxyphenyl)-2,3-dihydro-1H-inden-1-yl) carbamate; (S)-Quinuclidin-3-yl (5-(3-isopropoxyphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-butoxyphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-isobutoxyphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,5-dimethoxyphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3,5-dimethoxyphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-chloro-4-methoxyphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-ethoxy-3-fluorophenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-isopropoxy-3,5-dimethylphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-ethylphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-fluoro-2,2-dimethyl-5-(4-propylphenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-fluoro-5-(4-isopropylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-fluoro-5-(4-isobutylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-(tert-butyl)phenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-cyclopropylphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-fluoro-5-(4-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-ethoxyphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-fluoro-2,2-dimethyl-5-(4-propoxyphenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-fluoro-5-(4-isopropoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-chloro-4-isopropoxyphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-fluoro-5-(2-fluoro-4-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-butoxyphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-fluoro-5-(4-isobutoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(6-(cyclopropylmethoxy)pyridin-3-yl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(5-chloro-2-methoxyphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-butylphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-fluoro-5-(4-methoxy-3,5-dimethylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-ethoxy-3,5-dimethylphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-butoxy-3,5-dimethylphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-fluoro-5-(2-methoxypyridin-4-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-fluoro-5-(3-fluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-ethylphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-fluoro-5-(3-isobutylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-fluoro-5-(3-isopropylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-(tert-butyl)phenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-fluoro-5-(3-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-ethoxyphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-fluoro-2,2-dimethyl-5-(3-propoxyphenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-fluoro-5-(3-isopropoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-butoxyphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-fluoro-5-(3-isobutoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,4-dimethoxyphenyl)-6-fluoro-2, (S)-Quinuclidin-3-yl (5-(2,5-dimethoxyphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2,6-dimethoxyphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3,5-dimethoxyphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3,4-dimethoxyphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-chloro-4-methoxyphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(4-ethoxy-3-fluorophenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-fluoro-5-(4-isopropoxy-3,5-dimethylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5'-(4-fluorophenyl)-1',3'-dihydrospiro[cyclopropane-1,2'-inden]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (5'-(4-chlorophenyl)-1',3'-dihydrospiro[cyclopropane-1,2'-inden]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (5'-(4-(trifluoromethyl)phenyl)-1',3'-dihydrospiro[cyclopropane-1,2'-inden]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (5'-(4-(trifluoromethoxy)phenyl)-1',3'-dihydrospiro[cyclopropane-1,2'-indene]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (5'-(3-chlorophenyl)-1',3'-dihydrospiro[cyclopropane-1,2'-indene]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (5'-(3-(trifluoromethyl)phenyl)-1',3'-dihydrospiro[cyclopropane-1,2'-indene]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (5'-(4-(2-methoxyethoxy)phenyl)-1',3'-dihydrospiro[cyclopropane-1,2'-indene]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (5'-(3-(2-methoxyethoxy)phenyl)-1',3'-dihydrospiro[cyclopropane-1,2'-indene]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (5'-(4-(methoxymethoxy)phenyl)-1',3'-dihydrospiro[cyclopropane-1,2'-indene]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (5'-(3-(methoxymethoxy)phenyl)-1',3'-dihydrospiro[cyclopropane-1,2'-indene]-1'-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-chlorophenyl)-3,3-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (5-(2-chlorophenyl)-3,3-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (3,3-dimethyl-5-(3-(trifluoromethyl)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (3,3-dimethyl-5-(3-(trifluoromethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (3,3-dimethyl-5-(2-(trifluoromethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-(trifluoromethyl)phenyl)-2,3-dihydrobenzofuran-3-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-(trifluoromethoxy)phenyl)-2,3-dihydrobenzofuran-3-yl)carbamate; (S)-Quinuclidin-3-yl (5-(3-fluorophenyl)-2,2-dimethyl-2,3-dihydrobenzofuran-3-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-fluorophenyl)-2,2-dimethyl-2,3-dihydrobenzofuran-3-yl)carbamate; (S)-Quinuclidin-3-yl (6-(3-chlorophenyl)-2,2-dimethyl-2,3-dihydrobenzofuran-3-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(3-(trifluoromethyl)phenyl)-2,3-dihydrobenzofuran-3-yl)carbamate; (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(3-(trifluoromethoxy)phenyl)-2,3-dihydrobenzofuran-3-yl)carbamate; and (S)-Quinuclidin-3-yl (6-(3-(2-methoxyethoxy)phenyl)-2,2-dimethyl-2,3-dihydrobenzofuran-3-yl)carbamate.

[0039] The compound of Formula 1 or a pharmaceutically acceptable salt thereof may be in the form of cis- or trans-geometric isomers. Unless otherwise specified, the compound of Formula 1 or a pharmaceutically acceptable salt thereof includes both cis-geometric isomers and trans-geometric isomers. Also, the compound of Formula 1 or a pharmaceutically acceptable salt thereof may have substituents containing asymmetric atoms. Thus, it may be in the form of a racemic mixture (RS) or in the form of optical isomers such as (R) isomers or (S) isomers. Unless otherwise specified, the compound of Formula 1 or a pharmaceutically acceptable salt thereof includes both the racemic mixture (RS) and each optical isomer such as (R) isomers or (S) isomers. Furthermore, the compound of Formula 1 or a pharmaceutically 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. Unless otherwise specified, the compound of Formula 1 or a pharmaceutically acceptable salt thereof includes both each diastereomer and a mixture thereof.

[0040] The compound of Formula 1 according to the present invention may be in the form of a pharmaceutically acceptable salt. The salt may be in the form of a conventional acid addition salt, for example, 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. Also, the salt includes salts derived from amino acids such as glycine, alanine, valine, isoleucine, serine, cysteine, cystine, aspartic acid, glutamine, lysine, arginine, tyrosine, or proline. Furthermore, the salt includes salts derived from sulfonic acids such as methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, or toluenesulfonic acid.

[0041] The compound of Formula 1 according to the present invention or a pharmaceutically acceptable salt thereof can be produced according to various methods.

[0042] For example, as shown in the following Reaction Scheme 1, the compound of Chemical Formula 1a according to the present invention or a pharmaceutically acceptable salt thereof can be produced by a production method including a step of reacting the compound of Chemical Formula 2 or a salt thereof with ethyl chloroformate to obtain a compound of Chemical Formula 3; a step of coupling the compound of Chemical Formula 3 with the compound of Chemical Formula 4 to obtain a compound of Chemical Formula 5; a step of reacting the compound of Chemical Formula 5 with an A-W-boronic acid substituted with X1, X2, X3, or X4 to obtain a compound of Chemical Formula 1a; and optionally, a step of converting the compound of Chemical Formula 1a into its pharmaceutically acceptable salt.

[0043]

Chemical Formula

[0044] In Reaction Scheme 1, X, Y, Z, W, A ring, X1, X2, X3, and X4 are the same as those defined above.

[0045] The compound of Chemical Formula 2 is a commercially available or known compound and may be synthesized according to the literature. The reaction of the compound of Chemical Formula 2 or a salt thereof with ethyl chloroformate may be carried out in the presence of an organic base such as triethylamine or N,N-diisopropylethylamine or an inorganic base such as potassium carbonate. The base may be used in an amount in the range of 1 to 1.5 equivalents relative to 1 equivalent of the compound of Chemical Formula 2, or in an amount in the range of 3 to 5 equivalents relative to 1 equivalent of a salt of the compound of Chemical Formula 2 (for example, hydrochloride). The reaction may be carried out in a solvent such as dichloromethane or tetrahydrofuran, preferably at 0°C to room temperature.

[0046] The coupling of the compound of Chemical Formula 3 with the compound of Chemical Formula 4 (that is, quinuclidinol) may be carried out by a condensation reaction including the removal of ethanol. The reaction may preferably be carried out in the presence of a base such as sodium hydride. Further, the reaction may be carried out in a nonpolar organic solvent such as toluene at 120°C to 140°C.

[0047] The reaction between the compound of Formula 5 and an A-W-boronic acid substituted with X1, X2, X3, or X4 may be carried out according to the Suzuki reaction. The Suzuki reaction may be carried out using a palladium catalyst such as tetrakis(triphenylphosphine)palladium(0) (Pd(PPh3)4), palladium(II) acetate (Pd(OAc)2), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (Pd(dppf)Cl2). Also, the Suzuki reaction may be carried out in the presence of an inorganic base such as cesium carbonate (Cs2CO3), sodium carbonate (Na2CO3), potassium carbonate (K2CO3), potassium phosphate (K3PO4). The Suzuki reaction may be carried out in a nonpolar organic solvent such as toluene or 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 the reaction time may be determined by known methods for the Suzuki reaction.

[0048] The conversion of the compound of Formula 1a to its pharmaceutically acceptable salt may be carried out according to a conventional method. For example, a pharmaceutically 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, and then adding a free acid or free base to crystallize.

[0049] Also, the compound of Formula 1a or a pharmaceutically acceptable salt thereof according to the present invention can be produced by a production method including the steps of: reacting the compound of Formula 4 with bis(4-nitrophenyl) carbonate to obtain a compound of Formula 7 as shown in the following Reaction Scheme 2; reacting the compound of Formula 7 with the compound of Formula 2 to obtain a compound of Formula 5; reacting the compound of Formula 5 with an A-W-boronic acid substituted with X1, X2, X3, or X4 to obtain a compound of Formula 1a; and optionally, converting the compound of Formula 1a to its pharmaceutically acceptable salt.

[0050] [Chemical formula]

[0051] In the above reaction formula 2, X, Y, Z, W, A ring, X1, X2, X3, and X4 are the same as those defined above.

[0052] The reaction between the compound of Chemical formula 4 (i.e., quinuclidinol) and bis(4-nitrophenyl) carbonate may be carried out in a polar solvent such as N,N-dimethylformamide, preferably at 0 °C to 25 °C. Also, the compound of Chemical formula 7 may be produced by reacting the compound of Chemical formula 4 with 4-nitrophenyl chloroformate in a solvent such as dichloromethane or acetonitrile in the presence of a base such as triethylamine.

[0053] The reaction between the compound of Chemical formula 7 and the compound of Chemical 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.

[0054] The reaction between the compound of Chemical formula 5 and the A-W-boronic acid substituted with X1, X2, X3, or X4 may be carried out according to the Suzuki reaction as described above. Also, the conversion of the compound of Chemical formula 1a to its pharmaceutically acceptable salt may be carried out according to the usual method as described above.

[0055] The compound having a 2,3-dihydro-1H-indenyl group or a 2,3-dihydrobenzofuran group according to the present invention, that is, the compound of Chemical formula 1 or its pharmaceutically acceptable salt has excellent inhibitory activity against glucosylceramide synthase (GCS). Therefore, the compound of Chemical formula 1 or its pharmaceutically acceptable salt can be usefully applied to the prevention or treatment of various diseases related to GCS.

[0056] Accordingly, the present invention includes, within its scope, a pharmaceutical composition for inhibiting glucosylceramide synthase (GCS), which comprises, as an active ingredient, a therapeutically effective amount of a compound of Chemical Formula 1 or a pharmaceutically acceptable salt thereof. In one embodiment, the present invention provides a pharmaceutical composition for preventing or treating GCS-related diseases such as Gaucher disease, Fabry disease, Tay-Sachs disease, Parkinson's disease, etc., which comprises, as an active ingredient, a therapeutically effective amount of a compound of Chemical Formula 1 or a pharmaceutically acceptable salt thereof.

[0057] The pharmaceutical composition of the present invention may include a pharmaceutically acceptable carrier such as a diluent, a disintegrant, a sweetening agent, a lubricant, or a flavoring agent. The pharmaceutical composition may be formulated into a preparation for oral administration such as tablets, capsules, powders, granules, suspensions, emulsions, or syrups; or a preparation for parenteral administration such as topical solutions, topical suspensions, topical emulsions, gels (e.g., ointments), inhalants, sprays, injections, etc. These preparations may be in various forms, for example, they may be in a single-dose dosage form or a repeated-dose dosage form.

[0058] The pharmaceutical composition of the present invention may include, for example, a diluent (e.g., lactose, corn starch, etc.); a lubricant (e.g., magnesium stearate, etc.); an emulsifying agent; a suspending agent; a stabilizing agent; and / or an isotonic agent, etc. Optionally, the composition may further include a sweetening agent and / or a flavoring agent.

[0059] The composition of the present invention may be administered orally or parenterally, including routes of administration such as inhalation, intravenous, intraperitoneal, subcutaneous, rectal, and topical surface. Therefore, the composition of the present invention can be formulated into various forms such as tablets, capsules, aqueous solutions or suspensions. In the case of tablets for oral administration, carriers such as lactose and corn starch and lubricants such as magnesium stearate are usually used. In the case of capsules for oral administration, lactose and / or dried corn starch can be used as diluents. When an aqueous suspension for oral administration is required, an emulsifier and / or a suspending agent can be incorporated into the active ingredient. If necessary, specific sweeteners and / or flavoring agents can be used. In the case of intramuscular, intraperitoneal, subcutaneous, and intravenous administration, usually, a sterile solution of the active ingredient needs to be prepared and the pH of the solution needs to be appropriately adjusted and buffered. In the case of intravenous administration, it is necessary to adjust the total concentration of the solutes to make the formulation isotonic. The composition of the present invention can be in the form of an aqueous solution containing a pharmaceutically acceptable carrier such as physiological saline having a pH value of 7.4. This solution can be introduced into the bloodstream in the muscle of the patient by local bolus injection.

[0060] The compound of Formula 1 or a pharmaceutically acceptable salt thereof can be administered to a subject patient in a therapeutically effective amount in the range of about 0.0001 mg / kg to about 100 mg / kg per day. Of course, the above dosage can be changed according to the age, weight, sensitivity, symptoms of the patient, or the activity of the compound.

[0061] The present invention includes, within its scope, a method for inhibiting glucosylceramide synthase (GCS) in a mammal, which includes administering a therapeutically effective amount of the compound of Formula 1 or a pharmaceutically acceptable salt thereof to a mammal in need thereof. In one embodiment, the present invention provides a method for treating diseases related to GCS such as Gaucher's disease, Fabry's disease, Tay-Sachs disease, Parkinson's disease, etc., which includes administering a therapeutically effective amount of the compound of Formula 1 or a pharmaceutically acceptable salt thereof to a mammal in need thereof.

[0062] The present invention also provides the use of a compound of Chemical Formula 1 or a pharmaceutically acceptable salt thereof for producing a medicament for inhibiting glucosylceramide synthase (GCS) in mammals. In one embodiment, the present invention provides the use of a compound of Chemical Formula 1 or a pharmaceutically acceptable salt thereof for producing a medicament for preventing or treating diseases associated with GCS such as Gaucher's disease, Fabry disease, Tay-Sachs disease, Parkinson's disease, and the like.

Examples

[0063] The following examples and test examples are for illustrative purposes of the present invention and do not limit the scope of the present invention.

[0064] In the following examples, brine means an aqueous solution of saturated sodium chloride. Unless otherwise specified, all temperatures are in degrees Celsius (°C). Unless otherwise specified, all reactions were carried out at room temperature.

[0065] The analysis of the compounds prepared in the following production examples and examples was carried out as follows: Nuclear magnetic resonance (NMR) spectral analysis was performed using a Bruker 400 MHz spectrometer, and chemical shifts (in ppm) were analyzed. Column chromatography was carried out using silica gel (Merck, 70 - 230 mesh). Each starting material is a known compound, and these were synthesized according to the literature or purchased commercially. All reactions and chromatographic fractions were analyzed by thin layer chromatography (TLC) on a 250 nm silica gel plate and visualized by ultraviolet light or iodine (I2) staining.

[0066] Production Example 1: (S)-Quinuclidin-3-yl (5-bromo-2,3-dihydro-1H-inden-1-yl) carbamate Step 1: Ethyl (5-bromo-2,3-dihydro-1H-inden-1-yl) carbamate 5-Bromo-2,3-dihydro-1H-inden-1-amine (2 g, 9.4 mmol) was dissolved in dichloromethane (50 ml), and then triethylamine (1.45 ml, 10.4 mmol) and ethyl chloroformate (1 ml, 10.4 mmol) were gradually added. The reaction mixture was stirred at room temperature for 4 hours. After adding water to the reaction mixture, it was extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The obtained pale yellow oily residue (2.6 g) was used in the next reaction without further purification.

[0067] Step 2: (S)-Quinuclidin-3-yl (5-bromo-2,3-dihydro-1H-inden-1-yl) carbamate (S)-(+)-3-Quinuclidinol (3.5 g, 27.5 mmol) was dissolved in toluene (80 ml), and then sodium hydride (219.6 mg, 9.2 mmol) was added at 0 °C. After stirring the reaction mixture for 15 minutes, ethyl (5-bromo-2,3-dihydro-1H-inden-1-yl) carbamate (2.6 g, 9.2 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. After adding brine to the reaction mixture, it was extracted with ethyl acetate. The organic layer was washed twice with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The obtained residue was purified by column chromatography (ethyl acetate / (methanol / ammonia water = 1 / 1) = 9 / 1, v / v) to obtain the title compound as a white solid. (1.3 g, yield: 46%) 1 H-NMR (400 MHz, CDCl3) δ 7.34 (s, 1H), 7.30 (m, 1H), 7.15 (m, 1H), 5.50 (br, 1H), 5.13 (m, 1H), 4.75 (m, 2H), 3.18 (m, 2H), 2.82 - 2.68 (m, 7H), 1.96 (m, 1H), 1.80 (m, 1H), 1.66 (m, 1H), 1.55 (m, 1H), 1.37 (m, 1H)

[0068] Production Example 2: (S)-Quinuclidin-3-yl (6-bromo-2,3-dihydro-1H-inden-1-yl) carbamate Using 6-bromo-2,3-dihydro-1H-inden-1-amine as the starting material, the title compound was produced according to the same procedure as in Production Example 1. 1 H-NMR (400 MHz, CDCl3) δ 7.40 (s, 1H), 7.30 (m, 1H), 7.08 (d, 1H), 5.51 (br, 1H), 5.19 (m, 1H), 4.75 (m, 2H), 3.20 (m, 2H), 2.82 - 2.69 (m, 7H), 1.97 (m, 1H), 1.80 (m, 1H), 1.67 (m, 1H), 1.55 (m, 1H), 1.38 (m, 1H)

[0069] Production Example 3: (S)-Quinuclidin-3-yl (6-bromo-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate Using 6-bromo-2,2-dimethyl-2,3-dihydro-1H-inden-1-amine as the starting material, the title compound was produced according to the same procedure as in Production Example 1. 1 H-NMR (400 MHz, CDCl3) δ 7.28 (m, 2H), 7.00 (d, 1H), 4.89 (m, 1H), 4.73 (m, 2H), 3.15 (m, 1H), 2.81 - 2.70 (m, 7H), 1.95 (m, 1H), 1.80 (br, 1H), 1.64 (br, 1H), 1.53 (br, 1H), 1.39 (br, 1H), 0.85 (d, 6H)

[0070] Production Example 4: (S)-Quinuclidin-3-yl (5-bromo-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate Step 1: 5-Bromo-2,2-dimethyl-2,3-dihydro-1H-inden-1-amine hydrochloride 5-Bromo-2,2-dimethyl-2,3-dihydro-1H-inden-1-one (100 g, 418.2 mmol) was dissolved in methanol (500 ml) and isopropanol (500 ml), and then ammonium acetate (515.8 g, 6691.5 mmol) and sodium cyanoborohydride (157.7 g, 2509.3 mmol) were gradually added at room temperature. The reaction mixture was stirred at room temperature for 4 hours and then refluxed with stirring at 80 °C for 22 hours. The reaction mixture was cooled to room temperature, basified to pH > 12 with 1N sodium hydroxide solution, 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 obtained residue, and then a hydrochloric acid solution (4M) in 1,4-dioxane was added. The mixture was stirred at room temperature for 1 hour. The obtained solid was filtered under reduced pressure, washed with ethyl acetate, and then dried to obtain the title compound as a white solid. (100 g, yield: 86.5%) 1 1H-NMR (400 MHz, CD3OD) δ 7.50 (m, 2H), 7.39 (d, 1H), 4.28 (s, 1H), 3.02 - 2.82 (m, 2H), 1.24 (s, 3H), 1.20 (s, 3H)

[0071] Step 2: (S)-Quinuclidin-3-yl (5-bromo-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate A solution of (S)-(+)-3-quinuclidinol (38.6 g, 303.7 mmol) and bis(4-nitrophenyl) carbonate (92.4 g, 303.7 mmol) in N,N-dimethylformamide (700 ml) was stirred at room temperature for 8 hours. The 5-bromo-2,2-dimethyl-2,3-dihydro-1H-inden-1-amine hydrochloride (70 g, 253.1 mmol) and diisopropylethylamine (132.3 ml, 759.2 mmol) prepared in Step 1 were added to the solution, and then stirred at room temperature overnight. The reaction mixture was diluted with water (500 ml), acidified to pH 1-2 with 1N aqueous hydrochloric acid, and then extracted with diisopropyl ether (300 ml × 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 obtained residue was dissolved in isopropyl acetate, and then heptane was added. The mixture was stirred at room temperature overnight. The obtained solid was filtered under reduced pressure, washed with heptane, and dried to obtain the title compound as a white solid. (56 g, yield: 56.3%) 1 H-NMR (400 MHz, CDCl3) δ 7.32 (m, 2H), 7.09 (m, 1H), 4.89 (m, 1H), 4.86 (m, 1H), 4.77 (m, 1H), 3.25 (m, 1H), 2.87 - 2.75 (m, 2H), 2.74 - 2.69 (m, 5H), 2.07 (m, 1H), 1.83 (br, 1H), 1.69 (br, 1H), 1.57 (br, 1H), 1.41 (br, 1H), 1.27 (s, 3H), 0.92 (s, 3H)

[0072] Production Example 5: (S)-Quinuclidin-3-yl (5-bromo-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate Step 1: 5-Bromo-2,2-diethyl-2,3-dihydro-1H-inden-1-one 5-Bromo-1-indanone (20 g, 94.8 mmol) was dissolved in tetrahydrofuran (100 ml), and then 60% sodium hydride (19 g, 473.8 mmol) was added at 0 °C. After the reaction mixture was stirred for 15 minutes, iodoethane (19.1 ml, 236.9 mmol) was gradually added at the same temperature. The reaction mixture was stirred overnight at room temperature. After water was added to the reaction mixture, 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. (17 g, yield: 67%) 1 1H-NMR (400 MHz, CDCl3) δ 7.61 (s, 1H), 7.58 (m, 1H), 7.51 (m, 1H), 2.97 (s, 2H), 1.65 (m, 2H), 1.62 (m, 2H), 0.77 (t, 6H)

[0073] Step 2: 5-Bromo-2,2-diethyl-2,3-dihydro-1H-inden-1-amine hydrochloride Using 5-bromo-2,2-diethyl-2,3-dihydro-1H-inden-1-one prepared in Step 1, the title compound was prepared according to the same procedure as in Step 1 of Production Example 4. 1 1H-NMR (400 MHz, MeOD) δ 7.49 (s, 1H), 7.45 (m, 2H), 4.38 (s, 1H), 3.07 (m, 1H), 2.83 (m, 1H), 1.70 (m, 2H), 1.40 (m, 2H), 1.09 (t, 3H), 0.88 (t, 3H)

[0074] Step 3: (S)-Quinuclidin-3-yl (5-bromo-2,2-diethyl-2,3-dihydro-1H-inden-1-yl) carbamate Using 5-bromo-2,2-diethyl-2,3-dihydro-1H-inden-1-amine hydrochloride prepared in Step 2, the title compound was prepared according to the same procedure as in Step 2 of Production Example 4. 11H-NMR (400 MHz, CDCl3) δ 7.32 (m, 2H), 7.09 (m, 1H), 5.01 (m, 1H), 4.85 (m, 1H), 4.76 (m, 1H), 3.25 (m, 1H), 2.8 - 2.70 (m, 7H), 2.10 (br, 1H), 1.80 (br, 1H), 1.69 (br, 1H), 1.55 (m, 3H), 1.49 (m, 2H), 1.40 (br, 1H), 0.95 (m, 3H), 0.81 (m, 3H)

[0075] Production Example 6: (S)-Quinuclidin-3-yl (5-bromo-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate Step 1: 5-Bromo-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one 5-Bromo-6-methoxy-2,3-dihydro-1H-inden-1-one (10 g, 43.7 mmol) was dissolved in tetrahydrofuran (50 ml), and then 60% sodium hydride (8.7 g, 218.3 mmol) was added at 0 °C. After stirring the reaction mixture for 15 minutes, iodomethane (10.9 ml, 174.6 mmol) was gradually added at the same temperature. The reaction mixture was stirred at room temperature overnight. After adding water to the reaction mixture, 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. (10 g, yield: 89%) 1 1H-NMR (400 MHz, CDCl3) δ 7.66 (s, 1H), 7.21 (s, 1H), 3.94 (s, 3H), 2.93 (s, 2H), 1.24 (s, 6H)

[0076] Step 2: 5-Bromo-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-amine hydrochloride Using the 5-bromo-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-one produced in Step 1, the title compound was produced according to the same procedure as in Step 1 of Production Example 4. 1 H-NMR (400 MHz, MeOD) δ 7.47 (s, 1H), 7.23 (s, 1H), 4.29 (s, 1H), 4.11 (s, 3H), 2.95 - 2.92 (m, 1H), 2.78 - 2.74 (m, 1H), 1.29 (m, 3H), 0.98 (m, 3H)

[0077] Step 3: (S)-Quinuclidin-3-yl (5-bromo-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate Using the 5-bromo-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-amine hydrochloride prepared in Step 2, the title compound was prepared according to the same procedure as in Step 2 of Production Example 4. 1 H-NMR (400 MHz, CDCl3) δ 7.34 (s, 1H), 6.77 (m, 1H), 4.87 (s, 2H), 4.78 (m, 1H), 3.85 (m, 3H), 3.25 (m, 1H), 2.78 - 2.61 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.69 (br, 1H), 1.57 (br, 1H), 1.44 (br, 1H), 1.21 (m, 3H), 0.95 (m, 3H)

[0078] Production Example 7: (S)-Quinuclidin-3-yl (5-bromo-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate Using 5-bromo-6-fluoro-2,3-dihydro-1H-inden-1-one as the starting material, the title compound was prepared according to the same procedure as in Production Example 6. 1 H-NMR (400 MHz, CDCl3) δ 7.34 (d, 1H), 7.01 (d, 1H), 4.91 (m, 1H), 4.84 (m, 1H), 4.69 (m, 1H), 3.25 (m, 1H), 2.93 - 2.72 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.40 (br, 1H), 1.27 (m, 3H), 0.92 (m, 3H)

[0079] Production Example 8: (S)-Quinuclidin-3-yl (5'-bromo-1',3'-dihydrospiro[cyclopropane-1,2'-inden]-1'-yl)carbamate Step 1: 5'-Bromospiro[cyclopropane-1,2'-inden]-1'(3'H)-one 5-Bromo-1-indanone (5 g, 23.7 mmol) was dissolved in N,N-dimethylformamide (100 ml), and then 60% sodium hydride (2.7 g, 35.5 mmol) was added at 0 °C. After the reaction mixture was stirred for 15 minutes, 1,2-dibromomethane (5.1 ml, 35.5 mmol) was gradually added at the same temperature. The reaction mixture was stirred at room temperature overnight. After water was added to the reaction mixture, 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. (3.5 g, yield: 62%) 1 1H-NMR (400 MHz, CDCl3) δ 7.69 (s, 1H), 7.65 (m, 1H), 7.55 (d, 1H), 3.15 (s, 2H), 1.47 (d, 2H), 1.19 (d, 2H)

[0080] Step 2: 5'-Bromo-1',3'-dihydrospiro[cyclopropane-1,2'-inden]-1'-amine hydrochloride Using 5'-bromospiro[cyclopropane-1,2'-inden]-1'(3'H)-one produced in Step 1, the title compound was produced according to the same procedure as in Step 1 of Production Example 4. 1 1H-NMR (400 MHz, MeOD) δ 7.56 (s, 1H), 7.52 (m, 1H), 7.45 (m, 1H), 4.25 (s, 1H), 3.45 (m, 1H), 2.71 (m, 1H), 1.15 (m, 1H), 0.92 (m, 2H), 0.82 (m, 1H)

[0081] Step 3: (S)-Quinuclidin-3-yl (5'-bromo-1',3'-dihydrospiro[cyclopropane-1,2'-indene]-1'-yl) carbamate Using the 5'-bromo-1',3'-dihydrospiro[cyclopropane-1,2'-indene]-1'-amine hydrochloride prepared in Step 2, the title compound was produced according to the same procedure as in Production Example 1. 1 1H-NMR (400 MHz, CDCl3) δ 7.36 (m, 2H), 7.24 (m, 1H), 4.92 (m, 1H), 4.91 (m, 1H), 4.74 (m, 1H), 3.25 (m, 1H), 3.00 (m, 2H), 2.87 - 2.68 (m, 5H), 1.97 (br, 1H), 1.79 (m, 1H), 1.67 (br, 1H), 1.56 (m, 1H), 1.41 (br, 1H), 0.91 (m, 2H), 0.81 (m, 1H), 0.59 (m, 1H)

[0082] Production Example 9: (S)-Quinuclidin-3-yl (5-bromo-3,3-dimethyl-2,3-dihydro-1H-indene-1-yl) carbamate Step 1: 6-Bromo-1,1-dimethyl-2,3-dihydro-1H-indene A solution of titanium(IV) chloride (1.0 M) in dichloromethane (28.4 ml) was gradually added to dichloromethane (20 ml) at -30°C under a nitrogen atmosphere. A solution of dimethylzinc (2.0 M) in toluene (16.6 ml) was gradually added to the mixture at the same temperature, and then the mixture was stirred for 30 minutes. A solution of 6-bromo-2,3-dihydro-1H-inden-1-one (2 g, 9.5 mmol) in dichloromethane (10 ml) was gradually added to the reaction mixture, and then the mixture was stirred at -10°C for 4 hours. The reaction was quenched by adding ice water to the reaction mixture, and then the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-hexane / ethyl acetate = 5 / 1, v / v) to obtain the title compound as a white solid. (2.1 g, yield: 99%) 11H NMR (400 MHz, CDCl3) δ 7.28 (s, 1H), 7.20 (d, 1H), 7.07 (d, 1H), 2.85 (t, 2H), 1.94 (t, 2H), 1.26 (s, 6H)

[0083] Step 2: 5-Bromo-3,3-dimethyl-2,3-dihydro-1H-inden-1-one 6-Bromo-1,1-dimethyl-2,3-dihydro-1H-indene (1.9 g, 8.4 mmol) prepared in Step 1 was dissolved in acetone (20 ml), and then a solution of anhydrous magnesium sulfate (2.5 g, 21.1 mmol) in water (10 ml) was gradually added. Potassium permanganate (4 g, 25.3 mmol) was gradually added to the reaction mixture, and then the mixture was refluxed and stirred for 5 hours. After the reaction mixture was cooled to room temperature, it was filtered and concentrated under reduced pressure. The obtained residue was diluted with ethyl acetate, washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-hexane / ethyl acetate = 5 / 1, v / v) to obtain the title compound as a white solid. (1.85 g, yield: 92%) 1 1H NMR (400 MHz, CDCl3) δ 7.65 (s, 1H), 7.58 - 7.47 (m, 2H), 2.58 (s, 2H), 1.42 (s, 6H)

[0084] Step 3: 5-Bromo-3,3-dimethyl-2,3-dihydro-1H-inden-1-amine hydrochloride Using 5-Bromo-3,3-dimethyl-2,3-dihydro-1H-inden-1-one prepared in Step 2, the title compound was prepared according to the same procedure as in Step 1 of Production Example 4. The product was used in the next reaction without additional purification.

[0085] Step 4: Ethyl (5-bromo-3,3-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate Using 5-Bromo-3,3-dimethyl-2,3-dihydro-1H-inden-1-amine hydrochloride prepared in Step 3, the title compound was prepared according to the same procedure as in Step 1 of Production Example 1. 1 1H NMR (400 MHz, CDCl3) δ 7.35 (d, 1H), 7.30 (s, 1H), 7.16 (d, 1H), 5.24 (q, 1H), 4.81 (brd, 1H), 4.17 (q, 2H), 2.46 (m, 1H), 1.73 - 1.68 (m, 1H), 1.37 (s, 3H), 1.28 (t, 3H), 1.22 (s, 3H)

[0086] Step 5: (S)-Quinuclidin-3-yl (5-bromo-3,3-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate Using ethyl (5-bromo-3,3-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate prepared in Step 4, the title compound was produced according to the same procedure as in Step 2 of Production Example 1. 1 1H NMR (400 MHz, MeOD) δ 7.38 - 7.33 (m, 2H), 7.14 (dd, 1H), 5.14 (t, 1H), 4.80 - 4.75 (m, 1H), 3.30 - 3.21 (m, 1H), 2.90 - 2.69 (m, 5H), 2.39 - 2.32 (m, 1H), 2.11 - 2.04 (m, 1H), 1.99 - 1.90 (m, 1H), 1.84 - 1.74 (m, 2H), 1.70 - 1.61 (m, 1H), 1.55 - 1.45 (m, 1H), 1.39 (s, 3H), 1.22 (s, 3H)

[0087] Production Example 10: (S)-Quinuclidin-3-yl (6-bromo-2,3-dihydrobenzofuran-3-yl)carbamate Using 6-bromo-2,3-dihydrobenzofuran-3-amine as the starting material, the title compound was produced according to the same procedure as in Production Example 1. 1H-NMR (400 MHz, CDCl3) δ 7.21 (t, 1H), 7.08 - 7.06 (m, 1H), 7.02 (s, 1H), 5.35 - 5.31 (m, 2H), 4.73 - 4.68 (m, 2H), 4.41 - 4.37 (m, 1H), 3.24 - 3.19 (m, 1H), 2.82 - 2.66 (m, 5H), 2.05 - 1.98 (m, 1H), 1.75 - 1.66 (m, 2H), 1.56 - 1.55 (m, 1H), 1.40 - 1.38 (m, 1H)

[0088] Production Example 11: (S)-Quinuclidin-3-yl (5-bromo-2,2-dimethyl-2,3-dihydrobenzofuran-3-yl) carbamate Step 1: 5-Bromo-2,2-dimethylbenzofuran-3(2H)-one 5-Bromobenzofuran-3-one (2.75 g, 12.9 mmol) was dissolved in tetrahydrofuran (43 ml), and then 60% sodium hydride (2.07 g, 51.6 mmol) was added at 0 °C. After stirring the reaction mixture for 15 minutes, iodomethane (9.15 g, 64.5 mmol) was gradually added at the same temperature. The reaction mixture was stirred overnight at room temperature. After adding water to the reaction mixture, 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. (2.5 g, yield: 80%) 1 H-NMR (400 MHz, CDCl3) δ 7.81 (s, 1H), 7.79 (d, 1H), 6.98 (d, 1H), 1.47 (s, 6H)

[0089] Step 2: 5-Bromo-2,2-dimethyl-2,3-dihydrobenzofuran-3-amine Using the 5-bromo-2,2-dimethylbenzofuran-3(2H)-one produced in Step 1, the title compound was produced according to the same procedure as in Step 1 of Production Example 4. 1H-NMR (400 MHz, CDCl3) δ 7.40 (s, 1H), 7.27 (d, 1H), 6.63 (d, 1H), 4.12 (s, 1H), 1.41 (d, 6H)

[0090] Step 3: (S)-Quinuclidin-3-yl (5-bromo-2,2-dimethyl-2,3-dihydrobenzofuran-3-yl) carbamate Using 5-bromo-2,2-dimethyl-2,3-dihydrobenzofuran-3-amine prepared in Step 2, the title compound was produced according to the same procedure as in Production Example 1. 1 H-NMR (400 MHz, CDCl3) δ 7.40 (d, 1H), 7.31 (d, 1H), 6.65 (d, 1H), 5.36 (t, 1H), 5.00 (d, 1H), 4.78 - 4.69 (m, 1H), 3.25 - 3.15 (m, 1H), 2.89 - 2.59 (m, 5H), 2.06 - 2.00 (m, 1H), 1.83 - 1.74 (m, 1H), 1.72 - 1.63 (m, 1H), 1.60 - 1.51 (m, 1H), 1.48 (s, 3H), 1.41 - 1.36 (m, 4H)

[0091] Production Example 12: (S)-Quinuclidin-3-yl (6-bromo-2,2-dimethyl-2,3-dihydrobenzofuran-3-yl) carbamate Step 1: 6-Bromo-2,2-dimethylbenzofuran-3(2H)-one Using 6-bromobenzofuran-3(2H)-one as the starting material, the title compound was produced according to the same procedure as in Step 1 of Production Example 11. 1 H-NMR (400 MHz, CDCl3) δ 7.53 (d, 1H), 7.30 - 7.27 (m, 1H), 7.21 (dd, 1H), 1.47 (s, 6H)

[0092] Step 2: (S)-Quinuclidin-3-yl (6-bromo-2,2-dimethyl-2,3-dihydrobenzofuran-3-yl) carbamate Using 6-bromo-2,2-dimethylbenzofuran-3(2H)-one produced in Process 1, the title compound was produced according to the same procedure as in Production Example 4. 1 H-NMR (400 MHz, CDCl3) δ 7.14 (dd, 1H), 7.05 - 6.99 (m, 1H), 6.91 (s, 1H), 5.59 - 5.46 (m, 1H), 4.94 (d, 1H), 4.77 - 4.66 (m, 1H), 3.27 - 3.14 (m, 1H), 2.91 - 2.61 (m, 5H), 2.12 - 2.01 (m, 1H), 1.86 - 1.64 (m, 2H), 1.61 - 1.52 (m, 1H), 1.45 (s, 3H), 1.43 - 1.32 (m, 4H)

[0093] Example 1: (S)-Quinuclidin-3-yl (5-(4-fluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate To a mixture of (S)-quinuclidin-3-yl (5-bromo-2,3-dihydro-1H-inden-1-yl)carbamate (30 mg, 0.082 mmol) produced in Production Example 1, 4-fluorophenylboronic acid (17.2 mg, 0.12 mmol), potassium phosphate (52.3 mg, 0.25 mmol), and tetrakis(triphenylphosphine)palladium(0) (9.4 mg, 10 mol%), 1,4-dioxane (1 ml) and water (0.5 ml) were gradually added. After the reaction mixture was refluxed with stirring at 120 °C overnight, it was cooled to room temperature. After adding water to the reaction mixture, 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 silica gel column chromatography (ethyl acetate / (methanol / ammonia water = 1 / 1) = 9 / 1, v / v) to obtain the title compound as a white solid. (19 mg, yield: 64%) 11H-NMR (400 MHz, CDCl3) δ 7.55 (m, 2H), 7.42 (m, 3H), 7.13 (m, 2H), 5.29 (m, 1H), 5.00 (m, 1H), 4.81 (br, 1H), 3.28 (m, 1H), 3.05 (m, 1H), 2.94 (m, 3H), 2.82 (m, 3H), 2.65 (m, 1H), 2.06 (m, 1H), 1.93 - 1.88 (m, 2H), 1.71 (m, 1H), 1.60 (br, 1H), 1.42 (br, 1H)

[0094] Examples 2 - 24 (S)-Quinuclidin-3-yl (5-bromo-2,3-dihydro-1H-inden-1-yl) carbamate prepared in Production Example 1; and the corresponding substituted phenylboronic acid were each used to produce the title compounds of Examples 2 - 24 according to the same procedure as in Example 1.

[0095] Example 2: (S)-Quinuclidin-3-yl (5-(4-chlorophenyl)-2,3-dihydro-1H-inden-1-yl) carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.52 (m, 2H), 7.42 (m, 5H), 5.29 (m, 1H), 5.01 (m, 1H), 4.80 (br, 1H), 3.28 (m, 1H), 3.03 (m, 1H), 2.85 (m, 3H), 2.78 - 2.67 (m, 4H), 2.09 (m, 1H), 1.98 (m, 1H), 1.87 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.41 (br, 1H)

[0096] Example 3: (S)-Quinuclidin-3-yl (5-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-inden-1-yl) carbamate 1H-NMR (400 MHz, CDCl3) δ 7.69 (s, 4H), 7.47 (m, 3H), 5.31 (m, 1H), 5.01 (m, 1H), 4.81 (br, 1H), 3.31 (m, 1H), 3.04 (m, 1H), 2.94 (m, 3H), 2.78 (m, 4H), 2.03 (m, 2H), 1.91 (m, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.41 (br, 1H)

[0097] Example 4: (S)-Quinuclidin-3-yl (5-(4-(trifluoromethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.58 (d, 2H), 7.43 (m, 3H), 7.29 (d, 2H), 5.29 (m, 1H), 4.99 (m, 1H), 4.80 (br, 1H), 3.31 (m, 1H), 3.05 (m, 1H), 2.95 - 2.75 (m, 7H), 2.07 (m, 1H), 1.84 (m, 2H), 1.71 (br, 1H), 1.60 (br, 1H), 1.41 (br, 1H)

[0098] Example 5: (S)-Quinuclidin-3-yl (5-(3-fluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.70 (m, 1H), 7.45 (m, 5H), 7.05 (m, 1H), 5.28 (m, 1H), 4.98 (m, 1H), 4.80 (br, 1H), 3.31 (m, 1H), 2.94 (m, 1H), 2.82 - 2.75 (m, 7H), 2.09 (m, 1H), 1.82 (m, 2H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H)

[0099] Example 6: (S)-Quinuclidin-3-yl (5-(3-chlorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 11H-NMR (400 MHz, CDCl3) δ 7.57 (s, 1H), 7.45 (m, 4H), 7.34 (m, 2H), 5.29 (m, 1H), 4.98 (m, 1H), 4.81 (m, 1H), 3.30 (m, 1H), 3.04 (m, 1H), 2.95 - 2.66 (m, 7H), 2.09 (m, 1H), 1.82 (m, 2H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H)

[0100] Example 7: (S)-Quinuclidin-3-yl (5-(3-(trifluoromethyl)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.82 (s, 1H), 7.76 (d, 1H), 7.58 (m, 2H), 7.47 (m, 3H), 5.30 (m, 1H), 4.98 (m, 1H), 4.81 (m, 1H), 3.30 (m, 1H), 3.05 (m, 1H), 3.05 - 2.68 (m, 7H), 2.09 (m, 1H), 1.91 (br, 1H), 1.79 (m, 1H), 1.72 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H)

[0101] Example 8: (S)-Quinuclidin-3-yl (5-(3-(trifluoromethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.52 - 7.42 (m, 6H), 7.21 (m, 1H), 5.29 (m, 1H), 5.01 (m, 1H), 4.81 (m, 1H), 3.31 (m, 1H), 3.04 (m, 1H), 2.95 - 2.75 (m, 7H), 2.09 (m, 1H), 1.92 (m, 1H), 1.84 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.41 (br, 1H)

[0102] Example 9: (S)-Quinuclidin-3-yl (5-(2-fluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.42 (m, 3H), 7.28 - 7.16 (m, 4H), 5.29 (m, 1H), 4.98 (m, 1H), 4.81 (m, 1H), 3.29 (m, 1H), 2.95 (m, 1H), 2.89 - 2.66 (m, 7H), 2.06 (m, 1H), 1.83 (m, 1H), 1.74 (m, 2H), 1.60 (br, 1H), 1.41 (br, 1H)

[0103] Example 10: (S)-Quinuclidin-3-yl (5-(2-chlorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.49 (d, 1H), 7.41 (d, 1H), 7.32 (m, 5H), 5.32 (m, 1H), 4.99 (m, 1H), 4.81 (br, 1H), 3.30 (m, 1H), 3.03 (m, 1H), 2.95 - 2.67 (m, 7H), 2.06 (m, 1H), 1.91 (br, 1H), 1.83 (br, 1H), 1.73 (m, 1H), 1.61 (br, 1H), 1.41 (br, 1H)

[0104] Example 11: (S)-Quinuclidin-3-yl (5-(2-(trifluoromethyl)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.75 (d, 1H), 7.54 (m, 1H), 7.49 (m, 1H), 7.36 (m, 4H), 5.31 (m, 1H), 5.12 (m, 1H), 4.81 (br, 1H), 3.29 (m, 1H), 3.01 (m, 1H), 2.93 - 2.66 (m, 7H), 2.09 (br, 1H), 1.95 (m, 1H), 1.88 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.41 (br, 1H)

[0105] Example 12: (S)-Quinuclidin-3-yl (5-(2-(trifluoromethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.41 (m, 6H), 7.26 (m, 1H), 5.29 (m, 1H), 5.04 (m, 1H), 4.81 (m, 1H), 3.31 (m, 1H), 3.02 (m, 1H), 2.94 - 2.76 (m, 7H), 2.06 (m, 1H), 1.84 (m, 2H), 1.71 (br, 1H), 1.61 (br, 1H), 1.42 (br, 1H)

[0106] Example 13: (S)-Quinuclidin-3-yl (5-(p-tolyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.46 (m, 5H), 7.25 (m, 2H), 5.29 (m, 1H), 4.98 (m, 1H), 4.80 (m, 1H), 3.30 (m, 1H), 3.04 (m, 1H), 2.96 - 2.67 (m, 7H), 2.40 (s, 3H), 2.09 (m, 1H), 1.85 (m, 2H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H)

[0107] Example 14: (S)-Quinuclidin-3-yl (5-(4-(difluoromethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.58 (m, 2H), 7.41 (m, 3H), 7.20 (d, 2H), 6.75 - 6.38 (t, 1H), 5.29 (m, 1H), 4.98 (m, 1H), 4.80 (m, 1H), 3.30 (m, 1H), 2.95 - 2.66 (m, 7H), 2.08 (m, 1H), 1.85 (m, 2H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H)

[0108] Example 15: (S)-Quinuclidin-3-yl (5-(3,4-difluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 11H-NMR (400 MHz, CDCl3) δ 7.40 (m, 4H), 7.23 (m, 2H), 5.28 (m, 1H), 5.00 (m, 1H), 4.80 (m, 1H), 3.30 (m, 1H), 3.03 (m, 1H), 2.94 - 2.66 (m, 7H), 2.06 (m, 1H), 1.87 (m, 2H), 1.71 (br, 1H), 1.60 (br, 1H), 1.41 (br, 1H)

[0109] Example 16: (S)-Quinuclidin-3-yl (5-(2,4-difluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.40 (m, 4H), 6.96 (m, 2H), 5.30 (m, 1H), 5.00 (m, 1H), 4.80 (m, 1H), 3.28 (m, 1H), 3.03 (m, 1H), 2.95 - 2.66 (m, 7H), 2.06 (m, 1H), 1.82 (m, 2H), 1.71 (br, 1H), 1.60 (br, 1H), 1.41 (br, 1H)

[0110] Example 17: (S)-Quinuclidin-3-yl (5-(2,3-difluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.42 (m, 3H), 7.16 (m, 3H), 5.31 (m, 1H), 5.00 (m, 1H), 4.81 (m, 1H), 3.27 (m, 1H), 3.04 (m, 1H), 2.95 - 2.67 (m, 7H), 2.09 (m, 1H), 1.86 (m, 2H), 1.71 (br, 1H), 1.60 (br, 1H), 1.41 (br, 1H)

[0111] Example 18: (S)-Quinuclidin-3-yl (5-(2,5-difluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.41 (m, 3H), 7.12 (m, 2H), 7.01 (m, 1H), 5.30 (m, 1H), 5.02 (m, 1H), 4.81 (m, 1H), 3.30 (m, 1H), 3.03 (m, 1H), 2.95 - 2.66 (m, 7H), 2.09 (m, 1H), 1.89 (m, 2H), 1.71 (br, 1H), 1.60 (br, 1H), 1.41 (br, 1H)

[0112] Example 19: (S)-Quinuclidin-3-yl (5-(3,5-difluorophenyl)-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.42 (m, 3H), 7.09 (d, 2H), 6.79 (t, 1H), 5.29 (m, 1H), 4.98 (m, 1H), 4.81 (m, 1H), 3.30 (m, 1H), 3.04 (m, 1H), 2.97 - 2.67 (m, 7H), 2.09 (m, 1H), 1.90 (m, 1H), 1.82 (m, 1H), 1.71 (br, 1H), 1.61 (br, 1H), 1.42 (br, 1H)

[0113] Example 20: (S)-Quinuclidin-3-yl (5-(2,3,4-trifluorophenyl)-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.43 (m, 1H), 7.37 (m, 2H), 7.13 (m, 1H), 7.04 (m, 1H), 5.29 (m, 1H), 5.02 (m, 1H), 4.80 (m, 1H), 3.28 (m, 1H), 3.03 (m, 1H), 2.97 - 2.67 (m, 7H), 2.06 (m, 1H), 1.91 (m, 1H), 1.84 (m, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H)

[0114] Example 21: (S)-Quinuclidin-3-yl (5-(2,4,5-trifluorophenyl)-2,3-dihydro-1H-inden-1-yl) carbamate 1H-NMR (400 MHz, CDCl3) δ 7.45 (d, 1H), 7.36 (s, 2H), 7.21 (m, 1H), 7.02 (m, 1H), 5.30 (m, 1H), 5.01 (m, 1H), 4.81 (m, 1H), 3.28 (m, 1H), 3.04 (m, 1H), 2.95 - 2.67 (m, 7H), 2.09 (m, 1H), 1.90 (m, 2H), 1.71 (br, 1H), 1.60 (br, 1H), 1.41 (br, 1H)

[0115] Example 22: (S)-Quinuclidin-3-yl (5-(3,5-dichlorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.57 (m, 1H), 7.49 - 7.42 (m, 5H), 5.29 (m, 1H), 5.00 (m, 1H), 4.81 (m, 1H), 3.28 (m, 1H), 3.05 (m, 1H), 2.89 - 2.67 (m, 7H), 2.06 (m, 1H), 1.83 (m, 2H), 1.71 (br, 1H), 1.61 (br, 1H), 1.42 (br, 1H)

[0116] Example 23: (S)-Quinuclidin-3-yl (5-(3,4-dichlorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.66 (s, 1H), 7.52 (m, 2H), 7.42 (m, 4H), 5.30 (m, 1H), 4.98 (m, 1H), 4.81 (m, 1H), 3.29 (m, 1H), 3.05 (m, 1H), 2.97 - 2.67 (m, 7H), 2.06 (m, 1H), 1.93 (m, 1H), 1.80 (m, 1H), 1.72 (br, 1H), 1.61 (br, 1H), 1.41 (br, 1H)

[0117] Example 24: (S)-Quinuclidin-3-yl (5-(2,5-dichlorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.42 (m, 1H), 7.32 (m, 2H), 7.28 (m, 3H), 5.31 (m, 1H), 5.07 (m, 1H), 4.80 (m, 1H), 3.28 (m, 1H), 3.03 (m, 1H), 2.94 - 2.66 (m, 7H), 2.06 (m, 1H), 1.94 (m, 1H), 1.87 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.41 (br, 1H)

[0118] Examples 25 - 48 (S)-Quinuclidin-3-yl (6-bromo-2,3-dihydro-1H-inden-1-yl)carbamate prepared in Production Example 2; and the corresponding substituted phenylboronic acid were each used to produce the title compounds of Examples 25 - 48 according to the same procedure as in Example 1.

[0119] Example 25: (S)-Quinuclidin-3-yl (6-(4-fluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.54 (m, 3H), 7.42 (m, 1H), 7.33 (m, 1H), 7.13 (t, 2H), 5.31 (m, 1H), 5.00 (m, 1H), 4.80 (m, 1H), 3.28 (m, 1H), 3.02 (m, 1H), 3.00 - 2.72 (m, 7H), 2.06 (m, 2H), 1.93 (m, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.41 (br, 1H)

[0120] Example 26: (S)-Quinuclidin-3-yl (6-(4-chlorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 11H-NMR (400 MHz, CDCl3) δ 7.52 (m, 3H), 7.40 (m, 3H), 7.33 (m, 1H), 5.31 (m, 1H), 5.03 (m, 1H), 4.80 (br, 1H), 3.28 (m, 1H), 3.00 (m, 1H), 2.93 - 2.66 (m, 7H), 1.91 (m, 2H), 1.85 (m, 1H), 1.72 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H)

[0121] Example 27: (S)-Quinuclidin-3-yl (6-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.69 (s, 4H), 7.55 (s, 1H), 7.49 (d, 1H), 7.36 (d, 1H), 5.33 (m, 1H), 5.04 (m, 1H), 4.81 (br, 1H), 3.28 (m, 1H), 3.02 (m, 1H), 2.94 - 2.67 (m, 7H), 1.93 (m, 2H), 1.83 (m, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.41 (br, 1H)

[0122] Example 28: (S)-Quinuclidin-3-yl (6-(4-(trifluoromethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.60 (d, 2H), 7.58 (s, 1H), 7.46 (d, 1H), 7.34 (d, 1H), 7.28 (d, 2H), 5.32 (m, 1H), 5.04 (m, 1H), 4.80 (br, 1H), 3.28 (m, 1H), 3.09 (m, 1H), 2.93 - 2.86 (m, 3H), 2.76 (m, 4H), 1.97 (m, 1H), 1.90 (m, 1H), 1.83 (m, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.39 (br, 1H)

[0123] Example 29: (S)-Quinuclidin-3-yl (6-(3-fluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.52 (s, 1H), 7.46 (d, 1H), 7.37 (m, 3H), 7.28 (m, 1H), 7.04 (m, 1H), 5.31 (m, 1H), 5.02 (m, 1H), 4.81 (br, 1H), 3.31 (m, 1H), 3.04 (m, 1H), 2.88 (m, 3H), 2.77 (m, 4H), 2.06 (m, 1H), 1.93 (m, 1H), 1.84 (m, 1H), 1.68 (m, 1H), 1.60 (br, 1H), 1.41 (br, 1H)

[0124] Example 30: (S)-Quinuclidin-3-yl (6-(3-chlorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.56 - 7.45 (m, 4H), 7.37 - 7.28 (m, 3H), 5.32 (m, 1H), 5.02 (m, 1H), 4.81 (br, 1H), 3.27 (m, 1H), 3.03 (m, 1H), 2.93 (m, 3H), 2.77 (m, 4H), 1.92 (m, 1H), 1.86 (m, 1H), 1.85 (m, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.41 (br, 1H)

[0125] Example 31: (S)-Quinuclidin-3-yl (6-(3-(trifluoromethyl)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.81 (s, 1H), 7.77 (m, 1H), 7.60 - 7.54 (m, 3H), 7.50 (m, 1H), 7.36 (m, 1H), 5.33 (m, 1H), 5.04 (m, 1H), 4.80 (br, 1H), 3.27 (m, 1H), 3.03 (m, 1H), 2.94 (m, 3H), 2.76 (m, 4H), 2.09 (m, 1H), 1.96 (m, 1H), 1.83 (m, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.41 (br, 1H)

[0126] Example 32: (S)-Quinuclidin-3-yl (6-(3-(trifluoromethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.51 (d, 2H), 7.46 (m, 2H), 7.42 (s, 1H), 7.35 (d, 1H), 7.21 (d, 1H), 5.30 (m, 1H), 5.05 (m, 1H), 4.80 (br, 1H), 3.30 (m, 1H), 3.02 (m, 1H), 2.87 (m, 3H), 2.70 (m, 4H), 2.08 (m, 1H), 2.00 (m, 1H), 1.90 (m, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H)

[0127] Example 33: (S)-Quinuclidin-3-yl (6-(2-fluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.49 (s, 1H), 7.43 (s, 2H), 7.33 (m, 2H), 7.22 (m, 1H), 7.18 (m, 1H), 5.31 (m, 1H), 5.05 (m, 1H), 4,78 (br, 1H), 3.27 (m, 1H), 3.03 (m, 1H), 2,91 (m, 3H), 2.75 (m, 4H), 1.95 (m, 2H), 1.88 (br, 1H), 1.69 (br, 1H), 1.58 (br, 1H), 1.39 (br, 1H)

[0128] Example 34: (S)-Quinuclidin-3-yl (6-(2-chlorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.48 (d, 1H), 7.39 (s, 1H), 7.32 (m, 5H), 5.31 (m, 1H), 5.07 (m, 1H), 4.77 (br, 1H), 3.24 (m, 1H), 3.04 (m, 1H), 2.94~2.71 (m, 7H), 1.99 (m, 1H), 1.90 (m, 1H), 1.81 (br, 1H), 1.68 (br, 1H), 1.57 (br, 1H), 1.38 (br, 1H)

[0129] Example 35: (S)-Quinuclidin-3-yl (6-(2-(trifluoromethyl)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.76 (d, 1H), 7.56 (m, 1H), 7.49 (m, 1H), 7.34 (m, 1H), 7.27 (m, 2H), 7.22 (m, 1H), 5.31 (m, 1H), 5.06 (m, 1H), 4.76 (br, 1H), 3.25 (m, 1H), 2.94 (m, 1H), 2.84 (m, 2H), 2.75 - 2.71 (m, 5H), 1.93 (m, 1H), 1.91 (m, 1H), 1.81 (m, 1H), 1.67 (m, 1H), 1.56 (br, 1H), 1.37 (br, 1H)

[0130] Example 36: (S)-Quinuclidin-3-yl (6-(2-(trifluoromethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.42 (s, 2H), 7.36 (m, 4H), 7.28 (s, 1H), 5.32 (m, 1H), 5.00 (m, 1H), 4.78 (br, 1H), 3.27 (m, 1H), 3.04 (m, 1H), 2.94 (m, 3H), 2.72 (m, 4H), 1.92 (m, 2H), 1.82 (m, 1H), 1.69 (br, 1H), 1.59 (br, 1H), 1.39 (br, 1H)

[0131] Example 37: (S)-Quinuclidin-3-yl (6-(4-(difluoromethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.58 (d, 2H), 7.50 (s, 1H), 7.45 (d, 1H), 7.33 (d, 1H), 7.21 (d, 2H), 6.75 - 6.38 (t, 1H), 5.31 (m, 1H), 5.02 (m, 1H), 4.79 (br, 1H), 3.28 (m, 1H), 3.01 (m, 1H), 2.90 (m, 3H), 2.72 (m, 4H), 2.06 (m, 1H), 1.93 (br, 1H), 1.83 (m, 1H), 1.70 (m, 1H), 1.58 (m, 1H), 1.40 (br, 1H)

[0132] Example 38: (S)-Quinuclidin-3-yl (6-(p-tolyl)-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.53 (s, 1H), 7.48 (m, 3H), 7.32 (d, 1H), 7.25 (m, 2H), 5.31 (m, 1H), 5.01 (m, 1H), 4.80 (br, 1H), 3.28 (m, 1H), 3.00 (m, 1H), 2.76 (m, 3H), 2.68 (m, 4H), 2.41 (s, 3H), 2.06 (m, 1H), 1.92 - 1.82 (m, 2H), 1.69 (m, 1H), 1.59 (br, 1H), 1.40 (br, 1H)

[0133] Example 39: (S)-Quinuclidin-3-yl (6-(3,4-difluorophenyl)-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.47 (s, 1H), 7.42 (m, 2H), 7.37 (m, 2H), 7.21 (m, 1H), 5.31 (m, 1H), 5.01 (m, 1H), 4.80 (br, 1H), 3.27 (m, 1H), 3.02 (m, 1H), 2.93 (m, 3H), 2.76 (m, 4H), 2.08 (m, 1H), 1.93 (m, 1H), 1.89 (m, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.41 (br, 1H)

[0134] Example 40: (S)-Quinuclidin-3-yl (6-(3,5-difluorophenyl)-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.50 (s, 1H), 7.44 (d, 1H), 7.32 (d, 1H), 7.10 (d, 2H), 6.79 (m, 1H), 5.31 (m, 1H), 5.03 (m, 1H), 4.80 (br, 1H), 3.28 (m, 1H), 3.03 (m, 1H), 2.93 - 2.67 (m, 7H), 2.09 (m, 1H), 1.92 (m, 1H), 1.84 (m, 1H), 1.70 (m, 1H), 1.61 (br, 1H), 1.40 (br, 1H)

[0135] Example 41: (S)-Quinuclidin-3-yl (6-(2,5-difluorophenyl)-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.47 (s, 1H), 7.42 (d, 1H), 7.34 (m, 1H), 7.10 (m, 2H), 7.01 (m, 1H), 5.30 (m, 1H), 5.04 (m, 1H), 4.79 (m, 1H), 3.26 (m, 1H), 3.04 (m, 1H), 2.87 - 2.75 (m, 7H), 2.06 (s, 1H), 1.93 (m, 1H), 1.88 (br, 1H), 1.69 (br, 1H), 1.59 (br, 1H), 1.40 (br, 1H)

[0136] Example 42: (S)-Quinuclidin-3-yl (6-(2,3-difluorophenyl)-2,3-dihydro-1H-inden-1-yl) carbamate 1H-NMR (400 MHz, CDCl3) δ 7.48 (s, 1H), 7.43 (m, 1H), 7.34 (d, 1H), 7.15 (m, 3H), 5.31 (m, 1H), 5.04 (m, 1H), 4.79 (m, 1H), 3.26 (m, 1H), 3.04 (m, 1H), 2.94 - 2.67 (m, 7H), 2.09 (m, 1H), 1.93 (m, 1H), 1.83 (br, 1H), 1.69 (br, 1H), 1.58 (br, 1H), 1.39 (br, 1H)

[0137] Example 43: (S)-Quinuclidin-3-yl (6-(2,4-difluorophenyl)-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.44 (s, 1H), 7.40 (m, 2H), 7.32 (m, 1H), 6.94 (m, 2H), 5.31 (m, 1H), 5.02 (m, 1H), 4.78 (m, 1H), 3.27 (m, 1H), 3.03 (m, 1H), 2.93 - 2.66 (m, 7H), 2.06 (m, 1H), 1.89 (m, 1H), 1.83 (br, 1H), 1.69 (br, 1H), 1.59 (br, 1H), 1.40 (br, 1H)

[0138] Example 44: (S)-Quinuclidin-3-yl (6-(2,4,5-trifluorophenyl)-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.43 (s, 1H), 7.36 (m, 2H), 7.23 (m, 1H), 7.04 (m, 1H), 5.31 (m, 1H), 5.02 (m, 1H), 4.79 (m, 1H), 3.26 (m, 1H), 3.02 (m, 1H), 2.93 - 2.72 (m, 7H), 2.06 (m, 1H), 1.88 (m, 1H), 1.83 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.41 (br, 1H)

[0139] Example 45: (S)-Quinuclidin-3-yl (6-(2,3,4-trifluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.44 (s, 1H), 7.33 (m, 2H), 7.13 (m, 1H), 7.04 (m, 1H), 5.31 (m, 1H), 5.01 (, 1H), 4.79 (m, 1H), 3.29 (m, 1H), 3.05 (m, 1H), 2.96 - 2.67 (m, 7H), 2.06 (m, 1H), 1.88 (m, 1H), 1.84 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.40 (br, 1H)

[0140] Example 46: (S)-Quinuclidin-3-yl (6-(2,5-dichlorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.49 (m, 2H), 7.32 (m, 3H), 7.25 (m, 1H), 5.32 (m, 1H), 5.01 (m, 1H), 4.79 (m, 1H), 3.27 (m, 1H), 3.04 (m, 1H), 2.97 - 2.68 (m, 7H), 2.06 (m, 1H), 1.93 (br, 1H), 1.88 (m, 1H), 1.69 (br, 1H), 1.58 (br, 1H), 1.39 (br, 1H)

[0141] Example 47: (S)-Quinuclidin-3-yl (6-(3,4-dichlorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.66 (s, 1H), 7.52 (m, 2H), 7.44 (m, 2H), 7.34 (m, 1H), 5.31 (m, 1H), 4.99 (m, 1H), 4.81 (br, 1H), 3.28 (m, 1H), 3.01 (m, 1H), 2.88 (m, 3H), 2.77 (m, 4H), 2.08 (m, 1H), 1.89 (m, 1H), 1.81 (m, 1H), 1.71 (m, 1H), 1.61 (m, 1H), 1.42 (br, 1H)

[0142] Example 48: (S)-Quinuclidin-3-yl (6-(3,5-dichlorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.48 (m, 2H), 7.45 (m, 2H), 7.34 (m, 2H), 5.31 (m, 1H), 5.00 (m, 1H), 4.81 (m, 1H), 3.30 (m, 1H), 3.03 (m, 1H), 2.95 - 2.68 (m, 7H), 2.10 (m, 1H), 1.91 (m, 1H), 1.82 (m, 1H), 1.70 (m, 1H), 1.59 (br, 1H), 1.41 (br, 1H)

[0143] Examples 49 - 72 Using (S)-quinuclidin-3-yl (6-bromo-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate prepared in Production Example 3; and the corresponding substituted phenylboronic acid respectively, the title compounds of Examples 49 - 72 were produced according to the same procedure as in Example 1.

[0144] Example 49: (S)-Quinuclidin-3-yl (6-(4-fluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.54 (m, 2H), 7.40 (m, 2H), 7.24 (t, 1H), 7.14 (t, 2H), 5.01 (m, 1H), 4.88 (m, 1H), 4.81 (m, 1H), 3.31 (m, 1H), 2.81 (m, 2H), 2.77 (m, 5H), 2.10 (m, 1H), 1.80 (br, 1H), 1.75 (br, 1H), 1.61 (br, 1H), 1.43 (br, 1H), 1.32 (d, 3H), 0.99 (d, 3H)

[0145] Example 50: (S)-Quinuclidin-3-yl (6-(4-chlorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.50 (m, 2H), 7.42 (m, 3H), 7.26 (m, 2H), 5.02 (m, 1H), 4.89 (m, 1H), 4.81 (m, 1H), 3.30 (m, 1H), 2.89 (m, 2H), 2.77 (m, 5H), 2.14 (m, 1H), 1.86 (br, 1H), 1.73 (br, 1H), 1.62 (br, 1H), 1.43 (br, 1H), 1.32 (d, 3H), 0.99 (d, 3H)

[0146] Example 51: (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.69 (s, 4H), 7.45 (m, 2H), 7.29 (d, 1H), 5.04 (m, 1H), 4.94 (m, 1H), 4.80 (m, 1H), 3.30 (m, 1H), 2.91 - 2.66 (m, 6H), 2.09 (s, 1H), 2.00 (br, 1H), 1.84 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H), 1.31 (d, 3H), 0.99 (d, 3H)

[0147] Example 52: (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(4-(trifluoromethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.60 (m, 2H), 7.41 (m, 2H), 7.29 (m, 3H), 5.03 (m, 1H), 4.95 (m, 1H), 4.80 (m, 1H), 3.29 (m, 1H), 2.88 - 2.66 (m, 6H), 2.09 (s, 1H), 2.00 (br, 1H), 1.85 (br, 1H), 1.71 (br, 1H), 1.59 (br, 1H), 1.42 (br, 1H), 1.34 (d, 3H), 0.99 (d, 3H)

[0148] Example 53: (S)-Quinuclidin-3-yl (6-(3-fluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.43(s, 2H), 7.39(m, 2H), 7.25(m, 2H), 7.04(t, 1H), 5.03(m, 1H), 4.89(m, 1H), 4.82(m, 1H), 3.30(m, 1H), 2.90(m, 2H), 2.78(m, 5H), 2.14(m, 1H), 1.85(br, 1H), 1.76(br, 1H), 1.61(br, 1H), 1.41(br, 1H), 1.32(d, 3H), 0.99(d, 3H)

[0149] Example 54: (S)-Quinuclidin-3-yl (6-(3-chlorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.57(s, 1H), 7.43(m, 2H), 7.38(m, 1H), 7.33(t, 1H), 7.25(m, 2H), 5.03(m, 1H), 4.90(m, 1H), 4.83(m, 1H), 3.31(m, 1H), 2.83(m, 2H), 2.78(m, 5H), 2.14(m, 1H), 1.88(br, 1H), 1.75(br, 1H), 1.60(br, 1H), 1.44(br, 1H), 1.32(d, 3H), 0.99(d, 3H)

[0150] Example 55: (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(3-(trifluoromethyl)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 11H-NMR (400 MHz, CDCl3) δ 7.82 (s, 1H), 7.76 (m, 1H), 7.58 (m, 2H), 7.45 (m, 2H), 7.30 (m, 1H), 5.04 (m, 1H), 4.91 (m, 1H), 4.81 (m, 1H), 3.29 (m, 1H), 2.87 (m, 2H), 2.79 (m, 5H), 2.14 (m, 1H), 1.85 (br, 1H), 1.76 (br, 1H), 1.61 (br, 1H), 1.42 (br, 1H), 1.32 (d, 3H), 1.00 (d, 3H)

[0151] Example 56: (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(3-(trifluoromethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.48 (m, 5H), 7.21 (m, 2H), 5.04 (m, 1H), 4.90 (m, 1H), 4.82 (m, 1H), 3.30 (m, 1H), 2.89 (m, 2H), 2.78 (m, 5H), 2.11 (m, 1H), 1.86 (br, 1H), 1.75 (br, 1H), 1.61 (br, 1H), 1.44 (br, 1H), 1.32 (d, 3H), 1.00 (d, 3H)

[0152] Example 57: (S)-Quinuclidin-3-yl (6-(2-fluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.43 (m, 2H), 7.31 - 7.16 (m, 5H), 5.03 (m, 1H), 4.91 (m, 1H), 4.80 (m, 1H), 3.30 (m, 1H), 2.89 (m, 2H), 2.78 (m, 5H), 2.09 (br, 1H), 1.85 (br, 1H), 1.74 (br, 1H), 1.59 (br, 1H), 1.42 (br, 1H), 1.31 (d, 3H), 1.00 (d, 3H)

[0153] Example 58: (S)-Quinuclidin-3-yl (6-(2-chlorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.48 (m, 1H), 7.30 (m, 6H), 5.04 (m, 1H), 4.91 (m, 1H), 4.79 (br, 1H), 3.30 (m, 1H), 2.87~2.75 (m, 7H), 2.08 (br, 1H), 1.79 (br, 1H), 1.69 (br, 1H), 1.58 (br, 1H), 1.42 (br, 1H), 1.32 (d, 3H), 0.99 (d, 3H)

[0154] Example 59: (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(2-(trifluoromethyl)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.76 (d, 1H), 7.56 (m, 1H), 7.49 (m, 1H), 7.34 (m, 1H), 7.20 (m, 3H), 5.03 (m, 1H), 4.89 (m, 1H), 4.79 (m, 1H), 3.26 (m, 1H), 2.88~2.71 (m, 7H), 2.09 (m, 1H), 1.81 (br, 1H), 1.71 (br, 1H), 1.58 (br, 1H), 1.41 (br, 1H), 1.33 (d, 3H), 0.99 (d, 3H)

[0155] Example 60: (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(p-tolyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.44 (m, 4H), 7.26 (m, 3H), 5.02 (m, 1H), 4.88 (m, 1H), 4.82 (m, 1H), 3.29 (m, 1H), 2.89~2.77 (m, 7H), 2.41 (s, 3H), 2.08 (br, 1H), 1.85 (br, 1H), 1.75 (br, 1H), 1.61 (br, 1H), 1.43 (br, 1H), 1.31 (d, 3H), 0.99 (d, 3H)

[0156] Example 61: (S)-Quinuclidin-3-yl (6-(4-(difluoromethoxy)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.58 (m, 2H), 7.50 (m, 2H), 7.25 (m, 1H), 7.20 (m, 2H), 6.75~6.38 (t, 1H), 5.03 (m, 1H), 4.89 (m, 1H), 4.81 (m, 1H), 3.31 (m, 1H), 2.90 (m, 2H), 2.78 (m, 5H), 2.11 (m, 1H), 1.87 (m, 1H), 1.71 (br, 1H), 1.61 (br, 1H), 1.43 (br, 1H), 1.31 (d, 3H), 1.00 (d, 3H)

[0157] Example 62: (S)-Quinuclidin-3-yl (6-(3,4-difluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.69 (m, 1H), 7.50 (m, 1H), 7.38 (m, 3H), 7.21 (m, 1H), 5.02 (m, 1H), 4.89 (m, 1H), 4.83 (m, 1H), 3.30 (m, 1H), 2.86 (m, 2H), 2.78 (m, 5H), 2.14 (m, 1H), 1.87 (br, 1H), 1.73 (br, 1H), 1.61 (br, 1H), 1.43 (br, 1H), 1.32 (d, 3H), 0.99 (d, 3H)

[0158] Example 63: (S)-Quinuclidin-3-yl (6-(2,4-difluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 11H-NMR (400 MHz, CDCl3) δ 7.48 (m, 3H), 7.28 (m, 1H), 6.94 (m, 2H), 5.03 (m, 1H), 4.90 (m, 1H), 4.81 (m, 1H), 3.28 (m, 1H), 2.88 (m, 3H), 2.78 (m, 4H), 2.14 (m, 1H), 1.87 (br, 1H), 1.75 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H), 1.32 (d, 3H), 0.99 (d, 3H)

[0159] Example 64: (S)-Quinuclidin-3-yl (6-(2,3-difluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.49 (m, 1H), 7.39 (m, 2H), 7.16 (m, 3H), 5.04 (m, 1H), 4.91 (m, 1H), 4.88 (m, 1H), 3.29 (m, 1H), 2.86 (m, 2H), 2.79 (m, 5H), 2.10 (m, 1H), 1.85 (br, 1H), 1.73 (br, 1H), 1.59 (br, 1H), 1.43 (br, 1H), 1.35 (d, 3H), 0.99 (d, 3H)

[0160] Example 65: (S)-Quinuclidin-3-yl (6-(2,5-difluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.60 (m, 1H), 7.39 (m, 2H), 7.13 (m, 2H), 7.02 (m, 1H), 5.03 (m, 1H), 4.91 (m, 1H), 4.81 (m, 1H), 3.31 (m, 1H), 2.86 (m, 2H), 2.78 (m, 5H), 2.14 (m, 1H), 1.87 (br, 1H), 1.75 (br, 1H), 1.60 (br, 1H), 1.43 (br, 1H), 1.32 (d, 3H), 0.99 (d, 3H)

[0161] Example 66: (S)-Quinuclidin-3-yl (6-(3,5-difluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.69~7.49 (m, 1H), 7.42 (m, 2H), 7.09 (m, 2H), 6.79 (m, 1H), 5.03 (m, 1H), 4.90 (m, 1H), 4.82 (m, 1H), 3.31 (m, 1H), 2.95 (m, 2H), 2.78 (m, 5H), 2.14 (m, 1H), 1.86 (br, 1H), 1.73 (br, 1H), 1.61 (br, 1H), 1.44 (br, 1H), 1.32 (d, 3H), 0.99 (d, 3H)

[0162] Example 67: (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(2,3,4-trifluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.34 (m, 1H), 7.28 (m, 2H), 7.13 (m, 1H), 7.07 (m, 1H), 5.03 (m, 1H), 4.91 (m, 1H), 4.80 (m, 1H), 3.29 (m, 1H), 2.88 (m, 2H), 2.79 (m, 5H), 2.10 (m, 1H), 1.85 (br, 1H), 1.70 (m, 1H), 1.61 (br, 1H), 1.42 (br, 1H), 1.31 (d, 3H), 1.00 (d, 3H)

[0163] Example 68: (S)-Quinuclidin-3-yl (2,2-dimethyl-(2,4,5-trifluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.34 (m, 2H), 7.28 (m, 2H), 7.04 (m, 1H), 5.03 (m, 1H), 4.90 (m, 1H), 4.80 (m, 1H), 3.28 (m, 1H), 2.98 (m, 2H), 2.78 (m, 5H), 2.10 (m, 1H), 1.85 (br, 1H), 1.73 (br, 1H), 1.60 (br, 1H), 1.43 (br, 1H), 1.32 (d, 3H), 0.98 (d, 3H)

[0164] Example 69: (S)-Quinuclidin-3-yl (6-(3,5-dichlorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.71 (m, 1H), 7.66 (m, 1H), 7.50 (m, 1H), 7.45 (m, 1H), 7.40 (m, 1H), 7.33 (m, 1H), 5.03 (m, 1H), 4.89 (m, 1H), 4.82 (m, 1H), 3.30 (m, 1H), 2.91 - 2.74 (m, 7H), 2.14 (m, 1H), 1.88 (br, 1H), 1.72 (br, 1H), 1.67 (br, 1H), 1.44 (br, 1H), 1.32 (d, 3H), 0.99 (d, 3H)

[0165] Example 70: (S)-Quinuclidin-3-yl (6-(3,4-dichlorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.69 (m, 2H), 7.50 (m, 2H), 7.39 (m, 2H), 5.02 (m, 1H), 4.89 (m, 1H), 4.82 (m, 1H), 3.31 (m, 1H), 2.90 (m, 2H), 2.78 (m, 5H), 2.14 (m, 1H), 1.87 (br, 1H), 1.74 (br, 1H), 1.62 (br, 1H), 1.44 (br, 1H), 1.32 (d, 3H), 0.99 (d, 3H)

[0166] Example 71: (S)-Quinuclidin-3-yl (6-(2,5-dichlorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.41 (m, 1H), 7.39 (m, 1H), 7.28 (m, 4H), 5.01 (m, 1H), 4.92 (m, 1H), 4.80 (m, 1H), 3.27 (m, 1H), 2.78 (m, 7H), 2.09 (m, 1H), 1.85 (br, 1H), 1.69 (br, 1H), 1.58 (br, 1H), 1.41 (br, 1H), 1.32 (d, 3H), 0.99 (d, 3H)

[0167] Example 72: (S)-Quinuclidin-3-yl (6-(4-(2-methoxyethoxy)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.51 (m, 2H), 7.40 (m, 2H), 7.21 (d, 1H), 6.99 (m, 2H), 4.98 (m, 1H), 4.84 (m, 1H), 4.80 (br, 1H), 4.17 (m, 2H), 3.78 (m, 2H), 3.47 (s, 3H), 3.25 (m, 1H), 2.88~2.71 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0168] Examples 73 to 275 Using (S)-quinuclidin-3-yl (5-bromo-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate produced in Production Example 4 and the corresponding substituted phenylboronic acid, the title compounds of Examples 73 to 275 were produced according to the same procedure as in Example 1.

[0169] Example 73: (S)-Quinuclidin-3-yl (5-(4-fluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.53 (m, 2H), 7.40 (m, 2H), 7.30 (m, 1H), 7.13 (t, 2H), 5.00 (m, 1H), 4.88 (m, 1H), 4.83 (m, 1H), 3.29 (m, 1H), 2.91 - 2.86 (m, 2H), 2.82 - 2.75 (m, 5H), 2.12 (br, 1H), 1.82 (br, 1H), 1.72 (br, 1H), 1.61 (br, 1H), 1.44 (br, 1H), 1.31 (d, 3H), 0.99 (d, 3H)

[0170] Example 74: (S)-Quinuclidin-3-yl (5-(4-chlorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.51 (d, 2H), 7.41 (d, 2H), 7.36 (m, 2H), 7.31 (m, 1H), 5.00 (m, 1H), 4.90 (m, 1H), 4.81 (br, 1H), 3.31 (m, 1H), 2.91 - 2.87 (m, 2H), 2.82 - 2.75 (m, 5H), 2.12 (br, 1H), 1.86 (br, 1H), 1.72 (br, 1H), 1.61 (br, 1H), 1.44 (br, 1H), 1.31 (d, 3H), 0.99 (d, 3H)

[0171] Example 75: (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-inden-1-yl) carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.67 (s, 4H), 7.46 - 7.44 (m, 1H), 7.42 (s, 1H), 7.35 - 7.27 (m, 1H), 5.02 (m, 1H), 4.89 (m, 1H), 4.82 (m, 1H), 3.29 (m, 1H), 2.90 - 2.85 (m, 2H), 2.81 - 2.77 (m, 5H), 2.13 (br, 1H), 1.83 (br, 1H), 1.72 (br, 1H), 1.62 (br, 1H), 1.4

[0172] Example 76: (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(4-(trifluoromethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.58 (d, 2H), 7.42 - 7.37 (m, 2H), 7.29 (m, 3H), 5.01 (m, 1H), 4.89 (m, 1H), 4.82 (m, 1H), 3.29 (m, 1H), 2.90 - 2.87 (m, 2H), 2.83 - 2.77 (m, 5H), 2.12 (br, 1H), 1.83 (br, 1H), 1.73 (br, 1H), 1.61 (br, 1H), 1.44 (br, 1H), 1.32 (d, 3H), 1.00 (d, 3H)

[0173] Example 77: (S)-Quinuclidin-3-yl (5-(3-fluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.44 - 7.37 (m, 3H), 7.34 (m, 1H), 7.31 (m, 2H), 7.04 (t, 1H), 5.01 (m, 1H), 4.90 (m, 1H), 4.81 (m, 1H), 3.29 (m, 1H), 2.89 - 2.87 (m, 2H), 2.83 - 2.75 (m, 5H), 2.11 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.61 (br, 1H), 1.43 (br, 1H), 1.32 (d, 3H), 1.00 (d, 3H)

[0174] Example 78: (S)-Quinuclidin-3-yl (5-(3-chlorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.56 (s, 1H), 7.45 (m, 2H), 7.40 (m, 2H), 7.34 (m, 1H), 7.30 (m, 1H), 5.01 (m, 1H), 4.96 (m, 1H), 4.81 (m, 1H), 3.28 (m, 1H), 2.89 - 2.86 (m, 2H), 2.82 - 2.75 (m, 5H), 2.11 (br, 1H), 1.86 (br, 1H), 1.72 (br, 1H), 1.61 (br, 1H), 1.43 (br, 1H), 1.32 (d, 3H), 0.99 (d, 3H)

[0175] Example 79: (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(3-(trifluoromethyl)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.82 (s, 1H), 7.75 (d, 1H), 7.60 - 7.56 (m, 2H), 7.43 (m, 2H), 7.35 (m, 1H), 5.03 (m, 1H), 4.92 (m, 1H), 4.81 (br, 1H), 3.29 (m, 1H), 2.89 - 2.84 (m, 2H), 2.81 - 2.77 (m, 5H), 2.12 (br, 1H), 1.84 (br, 1H), 1.72 (br, 1H), 1.61 (br, 1H), 1.44 (br, 1H), 1.33 (d, 3H), 1.00 (d, 3H)

[0176] Example 80: (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(3-(trifluoromethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.52 - 7.45 (m, 1H), 7.41 (m, 4H), 7.32 (m, 1H), 7.20 (d, 1H), 5.02 (m, 1H), 4.89 (m, 1H), 4.82 (m, 1H), 3.28 (m, 1H), 2.90 - 2.84 (m, 2H), 2.79 - 2.76 (m, 5H), 2.12 (br, 1H), 1.82 (br, 1H), 1.70 (br, 1H), 1.61 (br, 1H), 1.44 (br, 1H), 1.32 (d, 3H), 1.00 (d, 3H)

[0177] Example 81: (S)-Quinuclidin-3-yl (5-(2-fluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.43~7.37 (m, 3H), 7.33~7.28 (m, 2H), 7.23 (m, 1H), 7.18 (m, 1H), 5.01 (m, 1H), 4.91 (m, 1H), 4.81 (br, 1H), 3.30 (m, 1H), 2.89~2.87 (m, 2H), 2.83~2.76 (m, 5H), 2.12 (br, 1H), 1.85 (br, 1H), 1.72 (br, 1H), 1.61 (br, 1H), 1.43 (br, 1H), 1.32 (d, 3H), 1.00 (d, 3H)

[0178] Example 82: (S)-Quinuclidin-3-yl (5-(2-chlorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.47 (d, 1H), 7.33~7.25 (m, 6H), 5.02 (m, 1H), 4.94 (m, 1H), 4.82 (br, 1H), 3.28 (m, 1H), 2.89~2.87 (m, 2H), 2.83~2.75 (m, 5H), 2.13 (br, 1H), 1.85 (br, 1H), 1.72 (br, 1H), 1.61 (br, 1H), 1.43 (br, 1H), 1.34 (d, 3H), 1.00 (d, 3H)

[0179] Example 83: (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(2-(trifluoromethyl)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.74 (d, 1H), 7.55 (m, 1H), 7.48 (m, 1H), 7.33 (d, 1H), 7.27 (m, 1H), 7.17 (m, 1H), 7.14 (s, 1H), 5.03 (m, 2H), 4.82 (br, 1H), 3.31 (m, 1H), 2.89 - 2.85 (m, 2H), 2.82 - 2.73 (m, 5H), 2.11 (br, 1H), 1.85 (br, 1H), 1.71 (br, 1H), 1.61 (br, 1H), 1.44 (br, 1H), 1.32 (d, 3H), 1.00 (d, 3H)

[0180] Example 84: (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(2-(trifluoromethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.42 (m, 1H), 7.36 (m, 3H), 7.27 (m, 3H), 5.03 (m, 1H), 4.94 (m, 1H), 4.82 (m, 1H), 3.28 (m, 1H), 2.90 - 2.87 (m 2H), 2.83 - 2.75 (m, 5H), 2.12 (br, 1H), 1.85 (br, 1H), 1.72 (br, 1H), 1.62 (br, 1H), 1.44 (br, 1H), 1.32 (d, 3H), 1.00 (d, 3H)

[0181] Example 85: (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(p-tolyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.49 (d, 2H), 7.42 (m, 2H), 7.26 (m, 3H), 5.00 (m, 1H), 4.89 (m, 1H), 4.80 (m, 1H), 3.29 (m, 1H), 2.89 - 2.85 (m, 2H), 2.82 - 2.75 (m, 5H), 2.41 (s, 3H), 2.11 (br, 1H), 1.82 (br, 1H), 1.72 (br, 1H), 1.60 (br, 1H), 1.44 (br, 1H), 1.31 (d, 3H), 1.00 (d, 3H)

[0182] Example 86: (S)-Quinuclidin-3-yl (5-(4-(difluoromethoxy)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.56 (d, 2H), 7.37 (m, 2H), 7.32 (m, 1H), 7.19 (d, 2H), 6.75 - 6.38 (t, 1H), 4.99 (m, 1H), 2.90 (m, 1H), 4.82 (br, 1H), 3.29 (m, 1H), 2.90 - 2.87 (m, 2H), 2.83 - 2.79 (m, 5H), 2.11 (br, 1H), 1.82 (br, 1H), 1.72 (br, 1H), 1.60 (br, 1H), 1.44 (br, 1H), 1.32 (s, 3H), 0.99 (d, 3H)

[0183] Example 87: (S)-Quinuclidin-3-yl (5-(3,4-difluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.37 (m, 3H), 7.29 (m, 2H), 7.23 (m, 1H), 5.01 (m, 1H), 4.90 (m, 1H), 4.82 (m, 1H), 3.32 (m, 1H), 2.89 - 2.86 (m, 2H), 2.82 - 2.75 (m, 5H), 2.11 (m, 1H), 1.90 (br, 1H), 1.72 (br, 1H), 1.60 (br, 1H), 1.43 (br, 1H), 1.34 (d, 3H), 0.99 (d, 3H)

[0184] Example 88: (S)-Quinuclidin-3-yl (5-(2,5-difluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.36 (m, 3H), 7.12 (m, 2H), 6.99 (m, 1H), 5.02 (m, 1H), 4.90 (m, 1H), 4.80 (m, 1H), 3.29 (m, 1H), 2.89~2.87 (m, 2H), 2.83~2.75 (m, 5H), 2.11 (m, 1H), 1.86 (br, 1H), 1.72 (br, 1H), 1.61 (br, 1H), 1.43 (br, 1H), 1.32 (d, 3H), 1.00 (d, 3H)

[0185] Example 89: (S)-Quinuclidin-3-yl (5-(2,4-difluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.40 (m, 1H), 7.35 (m, 3H), 6.95 (m, 2H), 5.01 (m, 1H), 4.91 (m, 1H), 4.80 (m, 1H), 3.29 (m, 1H), 2.89~2.86 (m, 2H), 2.83~2.75 (m, 5H), 2.11 (m, 1H), 1.85 (br, 1H), 1.75 (br, 1H), 1.60 (br, 1H), 1.43 (br, 1H), 1.32 (d, 3H), 0.99 (d, 3H)

[0186] Example 90: (S)-Quinuclidin-3-yl (5-(3,5-difluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.50 (m, 3H), 7.10 (m, 2H), 6.78 ((m, 1H), 5.02 (m, 1H), 4.89 (m, 1H), 4.81 (m, 1H), 3.30 (m, 1H), 2.90~2.87 (m, 2H), 2.83~2.75 (m, 5H), 2.12 (m, 1H), 1.86 (br, 1H), 1.75 (br, 1H), 1.61 (br, 1H), 1.45 (br, 1H), 1.32 (d, 3H), 0.99 (d, 3H)

[0187] Example 91: (S)-quinucidin-3-yl (5-(2,3-difluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.38~7.28 (m, 3H), 7.16 (m, 3H), 5.02 (m, 1H), 4.91 (m, 1H), 4.82 (m, 1H), 3.30 (m, 1H), 2.88 (m, 2H), 2.83~2.76 (m, 5H), 2.12 (m, 1H), 1.85 (br, 1H), 1.72 (br, 1H), 1.60 (br, 1H), 1.44 (br, 1H), 1.32 (d, 3H), 0.99 (d, 3H)

[0188] Example 92: (S)-quinucidin-3-yl (5-(3,4-dichlorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.71 (m, 2H), 7.56 (m, 1H), 7.48 (m, 2H), 7.39 (m, 1H), 5.03 (m, 1H), 4.86 (m, 2H), 3.31 (m, 1H), 2.91 (m, 2H), 2.86~2.78 (m, 5H), 2.13 (m, 1H), 1.86 (br, 1H), 1.75 (br, 1H), 1.68 (br, 1H), 1.46 (br, 1H), 1.32 (d 3H), 0.99 (d, 3H)

[0189] Example 93: (S)-quinucidin-3-yl (5-(2,5-dichlorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.41 (d, 1H), 7.33 - 7.23 (m, 5H), 5.03 (m, 1H), 4.94 (m, 1H), 4.82 (m, 1H), 3.28 (m, 1H), 2.90 - 2.87 (m, 2H), 2.83 - 2.75 (m, 5H), 2.11 (m, 1H), 1.85 (br, 1H), 1.71 (br, 1H), 1.61 (br, 1H), 1.44 (br, 1H), 1.32 (d, 3H), 0.99 (d, 3H)

[0190] Example 94: (S)-Quinuclidin-3-yl (5-(3,5-dichlorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.50 (m, 1H), 7.45 (m, 1H), 7.39 (s, 2H), 7.35 (d, 2H), 5.02 (m, 1H), 4.87 (m, 2H), 3.30 (m, 1H), 2.90 - 2.82 (m, 2H), 2.83 - 2.79 (m, 5H), 2.13 (br, 1H), 2.06 (br, 1H), 1.88 (br, 1H), 1.69 (br, 1H), 1.48 (br, 1H), 1.32 (d, 3H), 0.99 (d, 3H)

[0191] Example 95: (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(2,3,4-trifluorophenyl)-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.31 (m, 3H), 7.13 (m, 1H), 7.06 (m, 1H), 5.02 (m, 1H), 4.90 (m, 1H), 4.83 (m, 1H), 3.30 (m, 1H), 2.94 - 2.88 (m, 2H), 2.83 - 2.76 (m, 5H), 2.12 (m, 1H), 1.87 (br, 1H), 1.73 (m, 1H), 1.61 (br, 1H), 1.47 (br, 1H), 1.31 (d, 3H), 1.00 (d, 3H)

[0192] Example 96: (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(2,4,5-trifluorophenyl)-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.32 (m, 3H), 7.23 (m, 1H), 7.03 (m, 1H), 5.02 (m, 1H), 4.89 (m, 1H), 4.81 (m, 1H), 3.32 (m, 1H), 2.91 - 2.87 (m, 2H), 2.83 - 2.75 (m, 5H), 2.11 (m, 1H), 1.85 (br, 1H), 1.72 (br, 1H), 1.61 (br, 1H), 1.44 (br, 1H), 1.32 (d, 3H), 0.99 (d, 3H)

[0193] Example 97: (S)-Quinuclidin-3-yl (5-(4-(2-methoxyethoxy)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.49 (d, 2H), 7.39 (m, 1H), 7.36 (s, 1H), 7.27 (m, 1H), 7.00 (d, 2H), 4.98 (m, 1H), 4.84 (m, 1H), 4.80 (br, 1H), 4.18 (m, 2H), 3.78 (m, 2H), 3.48 (s, 3H), 3.25 (m, 1H), 2.90 - 2.75 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0194] Example 98: (S)-Quinuclidin-3-yl (5-(3-(2-methoxyethoxy)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 11H-NMR (400 MHz, CDCl3) δ 7.42 (m, 1H), 7.36 (s, 1H), 7.31 - 7.27 (m, 2H), 7.18 (m, 2H), 6.91 (d, 1H), 4.99 (m, 1H), 4.84 - 4.80 (m, 2H), 4.18 (m, 2H), 3.79 (m, 2H), 3.48 (s, 3H), 3.25 (m, 1H), 2.90 - 2.75 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0195] Example 99: (S)-Quinuclidin-3-yl (5-(2-(2-methoxyethoxy)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.40 (m, 2H), 7.32 - 7.27 (m, 3H), 7.04 - 7.98 (m, 2H), 4.99 (m, 1H), 4.84 (m, 1H), 4.80 (m, 1H), 4.10 (m, 2H), 3.68 (m, 2H), 3.38 (s, 3H), 3.25 (m, 1H), 2.90 - 2.75 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0196] Example 100: (S)-Quinuclidin-3-yl (5-(4-(methoxymethoxy)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.51 (d, 2H), 7.38 (m, 1H), 7.35 (s, 1H), 7.27 (m, 1H), 7.10 (d, 2H), 5.22 (s, 2H), 4.99 (m, 1H), 4.84 (m, 1H), 4.80 (m, 1H), 3.31 (s, 3H), 3.25 (m, 1H), 2.90 - 2.75 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0197] Example 101: (S)-Quinuclidin-3-yl (5-(3-(methoxymethoxy)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, MeOD) δ 7.41 (m, 2H), 7.28 (m, 1H), 7.26 (m, 1H), 7.05 (d, 1H), 7.00 (s, 1H), 6.75 (d, 1H), 5.07 (br, 1H), 4.87 (s, 2H), 3.72 (m, 1H), 3.67 (s, 3H), 3.39 (m, 2H), 3.39 - 3.29 (m, 5H), 2.81 (s, 2H), 2.45 (m, 1H), 2.30 (br, 1H), 2.10 (br, 1H), 1.93 (br, 1H), 1.24 (d, 3H), 0.98 (d, 3H)

[0198] Example 102: (S)-Quinuclidin-3-yl (5-(2-(methoxymethoxy)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.39 (m, 1H), 7.35 (m, 4H), 7.21 (m, 1H), 7.09 (m, 1H), 5.12 (s, 2H), 4.99 (m, 1H), 4.84 (m, 1H), 4.80 (m, 1H), 3.41 (s, 3H), 3.25 (m, 1H), 2.90 - 2.75 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0199] Example 103: (S)-Quinuclidin-3-yl (5-(3-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.44 (m, 1H), 7.39 (s, 1H), 7.31 - 7.27 (m, 2H), 7.15 (d, 1H), 7.10 (s, 1H), 6.89 (d, 1H), 4.98 (m, 1H), 4.88 (m, 1H), 4.79 (br, 1H), 3.87 (s, 3H), 3.25 (m, 1H), 2.90 - 2.74 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0200] Example 104: (S)-Quinuclidin-3-yl (5-(3-ethoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 11H-NMR (400 MHz, CDCl3) δ 7.44 (m, 1H), 7.39 (s, 1H), 7.31 - 7.27 (m, 2H), 7.15 (d, 1H), 7.10 (s, 1H), 6.89 (d, 1H), 4.98 (m, 1H), 4.88 (m, 1H), 4.79 (br, 1H), 4.11 (m, 2H), 3.25 (m, 1H), 2.90 - 2.74 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.45 (t, 4H), 1.29 (m, 3H), 0.98 (m, 3H)

[0201] Example 105: (S)-Quinuclidin-3-yl (5-(3-isopropoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.43 (m, 1H), 7.39 (s, 1H), 7.35 - 7.27 (m, 2H), 7.14 (d, 1H), 7.10 (s, 1H), 6.88 (d, 1H), 5.00 (m, 1H), 4.85 (m, 1H), 4.80 (br, 1H), 4.62 (m, 1H), 3.25 (m, 1H), 2.90 - 2.74 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H), 1.38 (d, 6H), 1.29 (m, 3H), 0.98 (m, 3H)

[0202] Example 106: (S)-Quinuclidin-3-yl (5-(3-(dimethylamino)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1H-NMR (400 MHz, CDCl3) δ 7.44 (m, 1H), 7.40 (s, 1H), 7.32 - 7.27 (m, 2H), 6.91 (m, 2H), 6.74 (d, 1H), 4.99 (m, 1H), 4.86 (m, 1H), 4.80 (br, 1H), 3.25 (m, 1H), 3.01 (s, 6H), 2.92 - 2.75 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H), 1.30 (m, 3H), 0.97 (m, 3H)

[0203] Example 107: (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(3-(methylthio)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.45 (s, 1H), 7.41 - 7.23 (m, 6H), 4.99 (m, 1H), 4.87 (m, 1H), 4.80 (br, 1H), 3.25 (m, 1H), 2.92 - 2.75 (m, 7H), 2.54 (s, 3H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H), 1.31 (m, 3H), 0.98 (m, 3H)

[0204] Example 108: (S)-Quinuclidin-3-yl (5-(3-ethylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.45 (d, 1H), 7.42 (s, 2H), 7.40 - 7.28 (m, 3H), 7.19 (d, 1H), 5.00 (m, 1H), 4.88 (m, 1H), 4.80 (br, 1H), 3.25 (m, 1H), 2.92 - 2.75 (m, 7H), 2.70 (m, 2H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H), 1.31 (t, 3H), 1.29 (m, 3H), 0.98 (m, 3H)

[0205] Example 109: (S)-Quinuclidin-3-yl (5-(3-isopropylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.43~7.34 (m, 5H), 7.28 (m, 1H), 7.22 (d, 1H), 5.00 (m, 1H), 4.88 (m, 1H), 4.80 (br, 1H), 3.25 (m, 1H), 2.98 (m, 1H), 2.92~2.75 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H), 1.30 (m, 9H), 0.98 (m, 3H)

[0206] Example 110: (S)-Quinuclidin-3-yl (5-(3-(tert-butyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.58 (s, 1H), 7.44 (d, 1H), 7.38 (s, 4H), 7.28 (m, 1H), 5.00 (m, 1H), 4.88 (m, 1H), 4.79 (br, 1H), 3.25 (m, 1H), 2.92~2.75 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H), 1.38 (s, 9H), 1.29 (m, 3H), 0.98 (m, 3H)

[0207] Example 111: (S)-Quinuclidin-3-yl (5-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.34~7.27 (m, 3H), 7.25 (m, 2H), 7.10 (d, 1H), 5.00 (m, 1H), 4.88 (m, 1H), 4.79 (br, 1H), 3.25 (m, 1H), 2.92~2.75 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0208] Example 112: (S)-Quinuclidin-3-yl (5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.38 (m, 1H), 7.36 (s, 1H), 7.25 (m, 1H), 7.09 (s, 1H), 7.05 (d, 1H), 6.91 (d, 1H), 4.98 (m, 1H), 4.88 (m, 1H), 4.79 (br, 1H), 4.29 (s, 4H), 3.25 (m, 1H), 2.92~2.73 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H), 1.29 (m, 3H), 0.97 (m, 3H)

[0209] Example 113: (S)-Quinuclidin-3-yl (5-(2,3-dihydrobenzofuran-5-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.41 (s, 1H), 7.36~7.30 (m, 3H), 7.25 (m, 1H), 6.84 (d, 1H), 4.98 (m, 1H), 4.88 (m, 1H), 4.79 (br, 1H), 4.62 (t, 2H), 3.25 (m, 3H), 2.92~2.73 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H), 1.29 (m, 3H), 0.97 (m, 3H)

[0210] Example 114: (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(3-(2-morpholinoethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.43 (d, 1H), 7.39 (s, 1H), 7.38 - 7.30 (m, 2H), 7.17 (d, 1H), 7.11 (s, 1H), 6.89 (d, 1H), 4.99 (m, 1H), 4.88 (m, 1H), 4.79 (br, 1H), 4.19 (t, 2H), 3.75 (m, 4H), 3.25 (m, 3H), 2.92 - 2.73 (m, 9H), 2.60 (m, 4H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0211] Example 115: (S)-Quinuclidin-3-yl (5-(4-(2-fluoroethoxy)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.52 (d, 2H), 7.35 (m, 2H), 7.26 (m, 1H), 7.00 (d, 2H), 4.99 (m, 1H), 4.87 (m, 2H), 4.81 (m, 1H), 4.71 (br, 1H), 4.31 - 4.22 (m, 2H), 3.25 (m, 3H), 2.90 - 2.74 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.59 (br, 1H), 1.42 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0212] Example 116: (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(4-(2,2,2-trifluoroethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.43~7.36 (m, 3H), 7.31~7.25 (m, 2H), 7.15 (s, 1H), 6.91 (d, 1H), 4.99 (m, 1H), 4.88 (m, 1H), 4.79 (br, 1H), 4.42 (q, 2H), 3.25 (m, 3H), 2.92~2.73 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0213] Example 117: (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(4-(2-morpholinoethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.50 (d, 2H), 7.39 (m, 2H), 7.24 (m, 1H), 6.97 (d, 2H), 4.98 (m, 1H), 4.88 (m, 1H), 4.79 (br, 1H), 4.16 (t, 2H), 3.76 (m, 4H), 3.25 (m, 3H), 2.92~2.73 (m, 9H), 2.60 (m, 4H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0214] Example 118: (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(2-(trifluoromethyl)pyridin-4-yl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 8.76 (d, 1H), 7.87 (s, 1H), 7.67 (d, 1H), 7.49 (m, 2H), 7.37 (m, 1H), 5.00 (m, 1H), 4.93 (m, 1H), 4.80 (br, 1H), 3.25 (m, 1H), 2.92~2.73 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H), 1.31 (m, 3H), 0.98 (m, 3H)

[0215] Example 119: (S)-Quinuclidin-3-yl (5-(2,5-dichloropyridin-4-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 8.44 (s, 1H), 7.30 (m, 1H), 7.19 (m, 3H), 4.96 (m, 1H), 4.86 (m, 1H), 4.80 (br, 1H), 3.25 (m, 1H), 2.92 - 2.73 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H), 1.31 (m, 3H), 0.98 (m, 3H)

[0216] Example 120: (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(4-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.39 (m, 1H), 7.33 (s, 1H), 7.25 (m, 1H), 7.07 (d, 1H), 7.03 (s, 1H), 6.72 (d, 1H), 4.99 (m, 1H), 4.88 (m, 1H), 4.79 (br, 1H), 4.33 (m, 2H), 3.29 (m, 2H), 3.25 (m, 1H), 2.92 (s, 3H), 2.91 - 2.73 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0217] Example 121: (S)-Quinuclidin-3-yl (5-(2-chloro-5-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 11H-NMR (400 MHz, CDCl3) δ 7.36 (d, 1H), 7.28 (m, 3H), 6.86 (m, 1H), 6.81 (m, 1H), 5.00 (m, 2H), 4.80 (br, 1H), 3.81 (s, 3H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H), 1.31 (m, 3H), 0.99 (m, 3H)

[0218] Example 122: (S)-Quinuclidin-3-yl (5-(3-chloro-4-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.59 (d, 1H), 7.44 (d, 1H), 7.37 (m, 1H), 7.25 (m, 1H), 6.98 (d, 1H), 4.98 (m, 2H), 4.80 (br, 1H), 3.94 (s, 3H), 3.25 (m, 1H), 2.88 - 2.73 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H), 1.31 (m, 3H), 0.98 (m, 3H)

[0219] Example 123: (S)-Quinuclidin-3-yl (5-(2-chloro-4-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.24 (m, 1H), 7.22 (m, 3H), 7.01 (s, 1H), 6.85 (d, 1H), 4.99 (s, 2H), 4.79 (br, 1H), 3.84 (s, 3H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H), 1.31 (m, 3H), 0.97 (m, 3H)

[0220] Example 124: (S)-Quinuclidin-3-yl (5-(2-chloro-3-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.31~7.22 (m, 4H), 6.94 (d, 2H), 4.99 (s, 2H), 4.79 (br, 1H), 3.95 (s, 3H), 3.25 (m, 1H), 2.91~2.74 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H), 1.31 (m, 3H), 0.98 (m, 3H)

[0221] Example 125: (S)-Quinuclidin-3-yl (5-(4-chloro-3-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.41~7.37 (m, 3H), 7.27 (m, 1H), 7.08 (m, 2H), 5.00 (m, 1H), 4.91 (m, 1H), 4.80 (br, 1H), 3.97 (s, 3H), 3.25 (m, 1H), 2.91~2.75 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0222] Example 126: (S)-Quinuclidin-3-yl (5-(2,3-dichloro-4-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.27 (m, 1H), 7.21 (m, 1H), 7.19 (d, 2H), 6.90 (d, 1H), 5.00 (s, 2H), 4.80 (br, 1H), 3.95 (s, 3H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0223] Example 127: (S)-Quinuclidin-3-yl (5-(3-chloro-4-isopropoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.59 (s, 1H), 7.39 (m, 2H), 7.33 (s, 1H), 7.26 (m, 1H), 7.00 (d, 1H), 4.96 (m, 2H), 4.79 (br, 1H), 4.60 (m, 1H), 3.25 (m, 1H), 2.88 - 2.73 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.38 (d, 6H), 1.30 (m, 3H), 0.97 (m, 3H)

[0224] Example 128: (S)-Quinuclidin-3-yl (5-(2-fluoro-4-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.35 - 7.27 (m, 4H), 6.77 (d, 1H), 6.69 (d, 1H), 4.97 (m, 2H), 4.80 (br, 1H), 3.84 (s, 3H), 3.25 (m, 1H), 2.89 - 2.73 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.38 (d, 6H), 1.30 (m, 3H), 0.98 (m, 3H)

[0225] Example 129: (S)-Quinuclidin-3-yl (5-(3-(dimethylamino)-4-fluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.39 (m, 1H), 7.30 (s, 1H), 7.25 (m, 1H), 7.09 (s, 1H), 7.04 (m, 2H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (br, 1H), 3.25 (m, 1H), 2.90 (s, 6H), 2.89 - 2.74 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.38 (d, 6H), 1.30 (m, 3H), 0.98 (m, 3H)

[0226] Example 130: (S)-Quinuclidin-3-yl (5-(chroman-6-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.37 (m, 1H), 7.33 (s, 1H), 7.25 (m, 3H), 6.85 (d, 1H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (br, 1H), 4.23 (m, 2H), 3.25 (m, 1H), 2.89 - 2.74 (m, 9H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0227] Example 131: (S)-Quinuclidin-3-yl (5-(4-cyclopropylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.47 (d, 2H), 7.42 (m, 1H), 7.38 (s, 1H), 7.25 (m, 1H), 7.13 (d, 2H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (br, 1H), 3.25 (m, 1H), 2.89 - 2.74 (m, 7H), 2.10 (br, 1H), 1.91 (m, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.98 (m, 6H), 0.74 (m, 2H)

[0228] Example 132: (S)-Quinuclidin-3-yl (5-(4-(dimethylamino)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.48 (d, 2H), 7.39 (m, 1H), 7.36 (s, 1H), 7.21 (m, 2H), 6.80 (d, 2H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (br, 1H), 3.25 (m, 1H), 3.00 (s, 6H), 2.89 - 2.73 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0229] Example 133: (S)-Quinuclidin-3-yl (5-(4-ethoxy-3-fluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.38 - 7.32 (m, 2H), 7.27 (m, 3H), 6.99 (t, 1H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (br, 1H), 4.15 (m, 2H), 3.25 (m, 1H), 2.89 - 2.73 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.48 (t, 3H), 1.40 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0230] Example 134: (S)-Quinuclidin-3-yl (5-(4-methoxy-3-(trifluoromethyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.76 (s, 1H), 7.69 (d, 1H), 7.31 (m, 2H), 7.27 (m, 1H), 7.07 (d, 1H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (br, 1H), 4.95 (s, 3H), 3.25 (m, 1H), 2.89 - 2.73 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.31 (m, 3H), 0.98 (m, 3H)

[0231] Example 135: (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(4-propoxyphenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.50 (d, 2H), 7.38 (m, 1H), 7.35 (s, 1H), 7.26 (m, 1H), 6.96 (d, 2H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (br, 1H), 3.96 (q, 2H), 3.25 (m, 1H), 2.89 - 2.73 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.84 (m, 2H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.31 (m, 3H), 1.06 (t, 3H), 0.98 (m, 3H)

[0232] Example 136: (S)-Quinuclidin-3-yl (5-(4-isobutoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.50 (d, 2H), 7.39 (m, 1H), 7.36 (s, 1H), 7.26 (m, 1H), 6.96 (d, 2H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (br, 1H), 3.77 (d, 2H), 3.25 (m, 1H), 2.89 - 2.73 (m, 7H), 2.10 (m, 2H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.31 (m, 3H), 1.05 (d, 6H), 0.98 (m, 3H)

[0233] Example 137: (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(thiophen-3-yl)-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.46 - 7.41 (m, 3H), 7.38 (m, 2H), 7.21 (m, 1H), 4.98 (m, 1H), 4.87 (m, 1H), 4.80 (br, 1H), 3.25 (m, 1H), 2.89 - 2.73 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.31 (m, 3H), 0.98 (m, 3H)

[0234] Example 138: (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(4-methylthiophen-3-yl)-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.28 - 7.16 (m, 4H), 7.02 (s, 1H), 4.99 (m, 1H), 4.87 (m, 1H), 4.80 (br, 1H), 3.25 (m, 1H), 2.26 (s, 3H), 2.89 - 2.73 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.31 (m, 3H), 0.98 (m, 3H)

[0235] Example 139: (S)-Quinuclidin-3-yl (5-(3-(2-(dimethylamino)ethoxy)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.28 (m, 1H), 7.24 (m, 4H), 6.94 (m, 2H), 4.99 (m, 1H), 4.87 (m, 1H), 4.80 (br, 1H), 4.07 (m, 2H), 3.25 (m, 1H), 2.89~2.73 (m, 9H), 2.35 (s, 6H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.31 (m, 3H), 0.98 (m, 3H)

[0236] Example 140: (S)-Quinuclidin-3-yl (5-(isoquinolin-8-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 9.31 (s, 1H), 8.51 (d, 1H), 7.82 (d, 1H), 7.72 (m, 2H), 7.52 (d, 1H), 7.36 (m, 3H), 5.24 (m, 1H), 5.07 (m, 1H), 4.81 (m, 1H), 3.25 (m, 1H), 2.89~2.73 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.35 (m, 3H), 0.98 (m, 3H)

[0237] Example 141: (S)-Quinuclidin-3-yl (5-(isoquinolin-5-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 9.31 (s, 1H), 8.47 (d, 1H), 7.99 (d, 1H), 7.71 (d, 1H), 7.65 (m, 2H), 7.39 - 7.27 (m, 3H), 5.05 (m, 2H), 4.82 (m, 1H), 3.25 (m, 1H), 2.89 - 2.73 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.34 (m, 3H), 0.98 (m, 3H)

[0238] Example 142: (S)-Quinuclidin-3-yl (5-(isoquinolin-4-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 9.25 (s, 1H), 8.44 (s, 1H), 8.04 (d, 1H), 7.91 (d, 1H), 7.65 (m, 2H), 7.38 (m, 3H), 5.09 (m, 2H), 4.82 (m, 1H), 3.25 (m, 1H), 2.89 - 2.73 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.35 (m, 3H), 0.99 (m, 3H)

[0239] Example 143: (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(quinolin-3-yl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 9.16 (s, 1H), 8.30 (s, 1H), 8.14 (d, 1H), 7.88 (d, 1H), 7.72 (m, 1H), 7.61 - 7.53 (m, 3H), 7.39 (m, 1H), 5.05 - 4.94 (m, 2H), 4.82 (m, 1H), 3.25 (m, 1H), 2.91 - 2.77 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.34 (m, 3H), 1.00 (m, 3H)

[0240] Example 144: (S)-Quinuclidin-3-yl (5-(4-isopropoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.48 (d, 1H), 7.37 (m, 1H), 7.35 (s, 1H), 7.25 (m, 1H), 6.95 (d, 2H), 4.98 (m, 1H), 4.88 (m, 1H), 4.80 (br, 1H), 4.61 (m, 1H), 3.25 (m, 1H), 2.89 - 2.74 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.36 (d, 6H), 1.30 (m, 3H), 0.98 (m, 3H)

[0241] Example 145: (S)-Quinuclidin-3-yl (5-(2-isopropoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.42 (m, 1H), 7.36 (s, 1H), 7.30 - 7.21 (m, 3H), 7.01 (m, 2H), 4.98 (m, 1H), 4.88 (m, 1H), 4.80 (br, 1H), 4.42 (m, 1H), 3.25 (m, 1H), 2.91 - 2.72 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.29 (m, 3H), 1.26 (d, 6H), 0.98 (m, 3H)

[0242] Example 146: (S)-Quinuclidin-3-yl (5-(4-(tert-butyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 11H-NMR (400 MHz, CDCl3) δ 7.53 (m, 2H), 7.47 (m, 2H), 7.26 (m, 2H), 7.24 (m, 1H), 4.98 (m, 1H), 4.88 (m, 1H), 4.80 (br, 1H), 3.25 (m, 1H), 2.91 - 2.72 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.36 (s, 9H), 1.29 (m, 3H), 0.98 (m, 3H)

[0243] Example 147: (S)-Quinuclidin-3-yl (5-(4-ethylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.50 (d, 2H), 7.43 (m, 1H), 7.38 (s, 1H), 7.27 (m, 3H), 4.98 (m, 1H), 4.88 (m, 1H), 4.80 (br, 1H), 3.25 (m, 1H), 2.91 - 2.72 (m, 7H), 2.69 (m, 2H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 6H), 0.98 (m, 3H)

[0244] Example 148: (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(4-morpholinophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.51 (d, 2H), 7.39 (m, 1H), 7.36 (s, 1H), 7.27 (m, 1H), 6.97 (d, 2H), 4.98 (m, 1H), 4.88 (m, 1H), 4.80 (br, 1H), 3.89 (m, 4H), 3.25 (m, 1H), 3.21 (m, 4H), 2.91 - 2.72 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0245] Example 149: (S)-Quinuclidin-3-yl (5-(4-(methoxymethyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.56 (d, 2H), 7.42 (m, 4H), 7.27 (m, 1H), 4.98 (m, 1H), 4.88 (m, 1H), 4.80 (br, 1H), 4.50 (s, 2H), 3.42 (s, 3H), 3.25 (m, 1H), 2.89 - 2.74 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.29 (m, 3H), 0.98 (m, 3H)

[0246] Example 150: (S)-Quinuclidin-3-yl (5-(4-(2,2-difluoroethoxy)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.53 (d, 2H), 7.39 (m, 2H), 7.27 (m, 1H), 6.99 (d, 2H), 6.25 - 5.98 (t, 1H), 4.98 (m, 2H), 4.79 (br, 1H), 4.21 (m, 2H), 3.25 (m, 1H), 2.90 - 2.73 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.29 (m, 3H), 0.97 (m, 3H)

[0247] Example 151: (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(3-methyl-4-morpholinophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.40~7.36 (m, 4H), 7.24 (m, 1H), 7.07 (d, 1H), 4.95 (m, 2H), 4.78 (br, 1H), 3.89 (m, 4H), 3.25 (m, 1H), 2.95 (m, 4H), 2.91~2.73 (m, 7H), 2.38 (s, 3H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0248] Example 152: (S)-Quinuclidin-3-yl (5-(3-fluoro-4-morpholinophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.34 (m, 2H), 7.26 (m, 2H), 7.23 (m, 1H), 6.98 (t, 1H), 4.96 (m, 1H), 4.91 (br, 1H), 4.78 (br, 1H), 3.90 (m, 4H), 3.25 (m, 1H), 3.14 (m, 4H), 2.91~2.73 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0249] Example 153: (S)-Quinuclidin-3-yl (5-(3-chloro-4-morpholinophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.60 (s, 1H), 7.45 (d, 1H), 7.36 (m, 2H), 7.26 (m, 1H), 7.10 (d, 1H), 4.99 (m, 1H), 4.91 (br, 1H), 4.78 (br, 1H), 3.90 (m, 4H), 3.25 (m, 1H), 3.09 (m, 4H), 2.91~2.73 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0250] Example 154: (S)-Quinuclidin-3-yl (5-(3,4-dihydro-2H-benzo[b][1,4]dioxepin-7-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.37 (m, 1H), 7.34 (s, 1H), 7.24 (m, 1H), 7.20 (s, 1H), 7.15 (d, 1H), 7.02 (d, 1H), 4.99 (m, 1H), 4.91 (br, 1H), 4.78 (br, 1H), 4.23 (m, 4H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.22 (m, 2H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.29 (m, 3H), 0.97 (m, 3H)

[0251] Example 155: (S)-Quinuclidin-3-yl (5-(3-(difluoromethyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.71 (m, 2H), 7.54 (m, 2H), 7.41 (m, 2H), 7.30 (m, 1H), 6.85 - 6.57 (t, 1H), 5.01 (m, 1H), 4.92 (br, 1H), 4.80 (br, 1H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.29 (m, 3H), 0.97 (m, 3H)

[0252] Example 156: (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(quinolin-8-yl)-2,3-dihydro-1H-inden-1-yl)carbamate 11H-NMR (400 MHz, CDCl3) δ 8.96 (m, 1H), 8.22 (d, 1H), 7.84 (d, 1H), 7.72 (m, 1H), 7.62 (d, 1H), 7.58 (m, 1H), 7.50 (s, 1H), 7.44 (d, 1H), 7.35 (d, 1H), 5.00 (m, 1H), 4.92 (br, 1H), 4.80 (br, 1H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.28 (m, 3H), 0.95 (m, 3H)

[0253] Example 157: (S)-Quinuclidin-­3-yl (5-(benzofuran-3-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.84 (d, 1H), 7.78 (s, 1H), 7.55 (d, 1H), 7.49 (m, 1H), 7.45 (s, 1H), 7.34 (m, 3H), 5.02 (m, 1H), 4.92 (br, 1H), 4.80 (br, 1H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.32 (m, 3H), 0.97 (m, 3H)

[0254] Example 158: (S)-Quinuclidin-­3-yl (5-(benzofuran-2-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 11H-NMR (400 MHz, CDCl3) δ 7.73 (d, 1H), 7.71 (s, 1H), 7.59 (d, 1H), 7.53 (d, 1H), 7.26 (m, 3H), 5.02 (m, 1H), 4.92 (br, 1H), 4.80 (br, 1H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.31 (m, 3H), 0.97 (m, 3H)

[0255] Example 159: (S)-Quinuclidin-3-yl (5-(4-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.50 (d, 2H), 7.38 (m, 1H), 7.35 (s, 1H), 7.26 (m, 1H), 6.97 (d, 2H), 4.99 (m, 1H), 4.92 (br, 1H), 4.79 (br, 1H), 3.85 (s, 3H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0256] Example 160: (S)-Quinuclidin-3-yl (5-(4-ethoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.50 (d, 2H), 7.38 (m, 1H), 7.35 (s, 1H), 7.26 (m, 1H), 6.95 (d, 2H), 4.99 (m, 1H), 4.92 (br, 1H), 4.79 (br, 1H), 4.08 (m, 2H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (t, 3H), 1.40 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0257] Example 161: (S)-Quinuclidin-3-yl (5-(4-isobutylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.50 (d, 2H), 7.44 (m, 1H), 7.39 (s, 1H), 7.26 (m, 1H), 7.20 (d, 2H), 4.99 (m, 1H), 4.92 (br, 1H), 4.79 (br, 1H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.51 (d, 2H), 2.10 (br, 1H), 1.90 (m, 1H), 1.87 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H), 0.93 (d, 6H)

[0258] Example 162: (S)-Quinuclidin-3-yl (5-(2,4-dichloro-3-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.34 (d, 2H), 7.26 (m, 2H), 7.20 (s, 1H), 7.02 (d, 1H), 4.99 (m, 2H), 4.79 (br, 1H), 3.94 (s, 3H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.87 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0259] Example 163: (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(4-propylphenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.50 (d, 2H), 7.42 (m, 1H), 7.39 (s, 1H), 7.25 (m, 3H), 4.99 (m, 1H), 4.92 (br, 1H), 4.79 (br, 1H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.61 (m, 2H), 2.10 (br, 1H), 1.87 (br, 1H), 1.67 (m, 3H), 1.59 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.98 (m, 6H)

[0260] Example 164: (S)-Quinuclidin-3-yl (5-(4-butylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.50 (d, 2H), 7.42 (m, 1H), 7.39 (s, 1H), 7.25 (m, 3H), 4.99 (m, 1H), 4.92 (br, 1H), 4.79 (br, 1H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.65 (m, 2H), 2.10 (br, 1H), 1.87 (br, 1H), 1.70 (br, 1H), 1.64 (m, 3H), 1.40 (m, 3H), 1.30 (m, 3H), 0.98 (m, 6H)

[0261] Example 165: (S)-Quinuclidin-3-yl (5-(2,3-dimethoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.38 (m, 1H), 7.36 (s, 1H), 7.23 (m, 1H), 7.10 (m, 1H), 6.92 (d, 2H), 4.99 (m, 1H), 4.92 (br, 1H), 4.79 (br, 1H), 3.91 (s, 3H), 3.58 (s, 3H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.87 (br, 1H), 1.70 (br, 1H), 1.64 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0262] Example 166: (S)-Quinuclidin-3-yl (5-(2,4-dimethoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.35 (m, 1H), 7.33 (s, 1H), 7.23 (m, 1H), 7.20 (d, 2H), 4.99 (m, 1H), 4.92 (br, 1H), 4.79 (br, 1H), 3.85 (s, 3H), 3.80 (s, 3H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.87 (br, 1H), 1.70 (br, 1H), 1.64 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0263] Example 167: (S)-Quinuclidin-3-yl (5-(2,5-dimethoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.39 (m, 1H), 7.33 (s, 1H), 7.26 (m, 1H), 6.87 (m, 3H), 4.99 (m, 1H), 4.92 (br, 1H), 4.79 (br, 1H), 3.81 (s, 3H), 3.76 (s, 3H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.87 (br, 1H), 1.70 (br, 1H), 1.64 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0264] Example 168: (S)-Quinuclidin-3-yl (5-(2,6-dimethoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1H-NMR (400 MHz, CDCl3) δ 7.26 (m, 2H), 7.19 (m, 1H), 7.15 (s, 1H), 6.65 (d, 2H), 4.99 (m, 1H), 4.92 (br, 1H), 4.79 (br, 1H), 3.71 (s, 6H), 3.25 (m, 1H), 2.91~2.74 (m, 7H), 2.10 (br, 1H), 1.87 (br, 1H), 1.70 (br, 1H), 1.64 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0265] Example 169: (S)-Quinuclidin-3-yl (5-(3,5-dimethoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.43 (m, 1H), 7.38 (s, 1H), 7.26 (m, 1H), 6.71 (s, 2H), 6.46 (s, 1H), 4.99 (m, 1H), 4.92 (br, 1H), 4.79 (br, 1H), 3.85 (s, 6H), 3.25 (m, 1H), 2.91~2.74 (m, 7H), 2.10 (br, 1H), 1.87 (br, 1H), 1.70 (br, 1H), 1.64 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0266] Example 170: (S)-Quinuclidin-3-yl (5-(4-ethoxy-3-(trifluoromethyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.75 (s, 1H), 7.66 (d, 1H), 7.34 (m, 2H), 7.26 (m, 1H), 7.04 (d, 1H), 5.00 (m, 1H), 4.92 (br, 1H), 4.79 (br, 1H), 4.

[0267] Example 171: (S)-Quinuclidin-3-yl (5-(2,5-difluoro-4-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.32(m, 3H), 7.16(m, 1H), 6.78(m, 1H), 4.99(m, 1H), 4.92(br, 1H), 4.79(br, 1H), 3.91(s, 3H), 3.25(m, 1H), 2.91~2.74(m, 7H), 2.10(br, 1H), 1.87(br, 1H), 1.70(br, 1H), 1.64(br, 1H), 1.40(br, 1H), 1.30(m, 3H), 0.98(m, 3H)

[0268] Example 172: (S)-Quinuclidin-3-yl (5-(2-fluoro-5-isopropoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.37(m, 2H), 7.26(m, 1H), 7.04(t, 1H), 6.91(m, 1H), 6.80(m, 1H), 4.99(m, 1H), 4.92(br, 1H), 4.79(br, 1H), 4.51(m, 1H), 3.25(m, 1H), 2.91~2.74(m, 7H), 2.10(br, 1H), 1.87(br, 1H), 1.70(br, 1H), 1.64(br, 1H), 1.40(br, 1H), 1.33(d, 6H), 1.30(m, 3H), 0.98(m, 3H)

[0269] Example 173: (S)-Quinuclidin-3-yl (5-(3,5-dimethyl-4-propoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 11H-NMR (400 MHz, CDCl3) δ 7.39 (m, 1H), 7.35 (s, 1H), 7.25 (m, 1H), 7.21 (s, 2H), 4.99 (m, 1H), 4.92 (br, 1H), 4.79 (br, 1H), 3.78 (t, 2H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.34 (s, 6H), 2.10 (br, 1H), 1.85 (m, 3H), 1.70 (br, 1H), 1.64 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 1.10 (t, 3H), 0.98 (m, 3H)

[0270] Example 174: (S)-Quinuclidin-3-yl (5-(4-ethoxy-3,5-dimethylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.39 (m, 1H), 7.35 (s, 1H), 7.25 (m, 1H), 7.22 (s, 2H), 4.99 (m, 1H), 4.92 (br, 1H), 4.79 (br, 1H), 3.91 (q, 2H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.34 (s, 6H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.64 (br, 1H), 1.44 (t, 3H), 1.40 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0271] Example 175: (S)-Quinuclidin-3-yl (5-(2-ethylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 11H-NMR (400 MHz, CDCl3) δ 7.31 (d, 2H), 7.25 (m, 2H), 7.18 (m, 2H), 7.11 (s, 1H), 4.99 (m, 1H), 4.92 (br, 1H), 4.79 (br, 1H), 4.12 (q, 2H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.64 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 1.10 (t, 3H), 0.98 (m, 3H)

[0272] Example 176: (S)-Quinuclidin-3-yl (5-(2-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.39 (m, 1H), 7.37 - 7.25 (m, 4H), 7.04 - 6.78 (m, 2H), 4.99 (m, 1H), 4.92 (br, 1H), 4.79 (br, 1H), 3.82 (s, 3H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.64 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0273] Example 177: (S)-Quinuclidin-3-yl (5-(2-ethoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.43 (m, 1H), 7.35 (s, 1H), 7.32 - 7.23 (m, 3H), 7.03 - 6.96 (m, 2H), 4.99 (m, 1H), 4.92 (br, 1H), 4.79 (br, 1H), 4.05 (q, 2H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.64 (br, 1H), 1.40 (br, 1H), 1.37 (t, 3H), 1.30 (m, 3H), 0.98 (m, 3H)

[0274] Example 178: (S)-Quinuclidin-3-yl (5-(2-chloro-5-(trifluoromethoxy)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.48 (d, 1H), 7.26 (m, 2H), 7.21 (d, 2H), 7.14 (d, 1H), 4.99 (m, 1H), 4.92 (br, 1H), 4.79 (br, 1H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.64 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0275] Example 179: (S)-Quinuclidin-3-yl (5-(4-fluoro-2-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.27 (m, 1H), 7.25 (m, 3H), 6.70 (m, 2H), 4.99 (m, 1H), 4.92 (br, 1H), 4.79 (br, 1H), 3.80 (s, 3H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.64 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0276] Example 180: (S)-Quinuclidin-3-yl (5-(4-methoxy-2-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.26 (m, 1H), 7.15 (m, 3H), 6.77 (m, 2H), 4.99 (m, 1H), 4.92 (br, 1H), 4.79 (br, 1H), 3.84 (s, 3H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.26 (s, 3H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.64 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0277] Example 181: (S)-Quinuclidin-3-yl (5-(4-(tert-butoxymethyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.54 (d, 2H), 7.40 (m, 4H), 7.26 (m, 1H), 4.99 (m, 1H), 4.92 (br, 1H), 4.79 (br, 1H), 4.48 (s, 2H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.64 (br, 1H), 1.40 (br, 1H), 1.32 (s, 9H), 1.30 (m, 3H), 0.99 (m, 3H)

[0278] Example 182: (S)-Quinuclidin-3-yl (5-(2-chloro-3-(trifluoromethyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.72 (d, 1H), 7.49 (d, 1H), 7.40 (m, 1H), 7.32 (m, 1H), 7.22 (m, 2H), 5.00 (m, 2H), 4.79 (br, 1H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.64 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0279] Example 183: (S)-Quinuclidin-3-yl (5-(2-chloro-4-(trifluoromethyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.74 (s, 1H), 7.57 (d, 1H), 7.43 (d, 1H), 7.33 - 7.23 (m, 3H), 5.00 (m, 2H), 4.79 (br, 1H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.64 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0280] Example 184: (S)-Quinuclidin-3-yl (5-(2,6-dimethoxypyridin-3-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.56 (d, 1H), 7.36 (m, 1H), 7.49 (m, 1H), 7.32 (s, 1H), 6.38 (d, 1H), 4.99 (m, 1H), 4.86 (br, 1H), 4.79 (br, 1H), 3.97 (s, 6H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.64 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0281] Example 185: (S)-Quinuclidin-3-yl (5-(6-(cyclopropylmethoxy)pyridin-3-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 8.32 (s, 1H), 7.78 (d, 1H), 7.33 (m, 3H), 6.83 (d, 1H), 4.99 (m, 1H), 4.86 (br, 1H), 4.79 (br, 1H), 4.15 (d, 2H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.64 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H), 0.63 (m, 2H), 0.37 (m, 2H)

[0282] Example 186: (S)-Quinuclidin-3-yl (5-(benzo[b]thiophen-2-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.67 (m, 2H), 7.57 (m, 3H), 7.48 (m, 2H), 7.30 (m, 1H), 4.99 (m, 1H), 4.86 (br, 1H), 4.79 (br, 1H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.64 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0283] Example 187: (S)-Quinuclidin-3-yl (5-(2-(tert-butoxy)pyridin-4-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 8.16 (d, 1H), 7.45 (m, 2H), 7.28 (m, 1H), 7.03 (d, 1H), 6.85 (s, 1H), 5.00 (m, 1H), 4.86 (br, 1H), 4.79 (br, 1H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.64 (br, 1H), 1.61 (s, 9H), 1.40 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0284] Example 188: (S)-Quinuclidin-3-yl (5-(6-methoxy-5-(trifluoromethyl)pyridin-3-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 8.50 (s, 1H), 8.03 (s, 1H), 7.33 (m, 3H), 5.00 (m, 1H), 4.86 (br, 1H), 4.79 (br, 1H), 4.09 (s, 3H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.64 (br, 1H), 1.61 (s, 9H), 1.40 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H)

[0285] Example 189: (S)-Quinuclidin-3-yl (5-(6-methoxynaphthalen-2-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.96 (s, 1H), 7.81 (m, 2H), 7.70 (m, 1H), 7.54 (m, 2H), 7.32 (m, 1H), 7.18 (m, 2H), 5.02 (m, 1H), 4.86 (br, 1H), 4.79 (br, 1H), 3.96 (s, 3H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.64 (br, 1H), 1.40 (br, 1H), 1.32 (m, 3H), 1.00 (m, 3H)

[0286] Example 190: (S)-Quinuclidin-3-yl (5-([1,1'-biphenyl]-3-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.78 (s, 1H), 7.66 (m, 2H), 7.56 (m, 1H), 7.50 (m, 5H), 7.39 (m, 2H), 7.33 (m, 1H), 5.05 (m, 1H), 4.92 (br, 1H), 4.82 (br, 1H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.64 (br, 1H), 1.40 (br, 1H), 1.32 (m, 3H), 1.00 (m, 3H)

[0287] Example 191: (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(quinoxalin-6-yl)-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 8.85 (d, 2H), 8.28 (s, 1H), 8.16 (m, 1H), 8.04 (m, 1H), 7.59 (m, 2H), 7.33 (m, 1H), 5.02 (m, 2H), 4.79 (br, 1H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.64 (br, 1H), 1.40 (br, 1H), 1.32 (m, 3H), 1.00 (m, 3H)

[0288] Example 192: (S)-Quinuclidin-3-yl (5-(3,5-dimethylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.41 (m, 2H), 7.26 (m, 1H), 7.19 (s, 2H), 6.99 (s, 1H), 4.99 (m, 1H), 4.81 (br, 1H), 4.79 (br, 1H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.38 (s, 6H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.64 (br, 1H), 1.40 (br, 1H), 1.31 (m, 3H), 0.99 (m, 3H)

[0289] Example 193: (S)-Quinuclidin-3-yl (5-(furan-2-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.54 (m, 1H), 7.49 (s, 1H), 7.45 (s, 1H), 7.23 (m, 1H), 6.63 (m, 1H), 6.47 (m, 1H), 4.99 (m, 1H), 4.81 (br, 1H), 4.79 (br, 1H), 3.25 (m, 1H), 2.91~2.74 (m, 7H), 2.38 (s, 6H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.64 (br, 1H), 1.40 (br, 1H), 1.31 (m, 3H), 0.99 (m, 3H)

[0290] Example 194: (S)-Quinuclidin-3-yl (5-(4-isopropoxy-3,5-dimethylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.40 (m, 1H), 7.36 (s, 1H), 7.25 (m, 3H), 4.98 (m, 1H), 4.81 (br, 1H), 4.79 (br, 1H), 4.13 (m, 1H), 3.25 (m, 1H), 2.91~2.74 (m, 7H), 2.33 (s, 6H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.64 (br, 1H), 1.40 (br, 1H), 1.33 (d, 6H), 1.31 (m, 3H), 0.99 (m, 3H)

[0291] Example 195: (S)-Quinuclidin-3-yl (5-(4-methoxy-3,5-dimethylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.39 (m, 1H), 7.35 (s, 1H), 7.27 (m, 3H), 4.99 (m, 1H), 4.81 (br, 1H), 4.79 (br, 1H), 3.76 (s, 3H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.35 (s, 6H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.64 (br, 1H), 1.40 (br, 1H), 1.33 (d, 6H), 1.31 (m, 3H), 0.99 (m, 3H)

[0292] Example 196: (S)-Quinuclidin-3-yl (5-(6-isopropoxypyridin-3-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 8.34 (s, 1H), 7.76 (d, 1H), 7.30 (m, 3H), 6.74 (d, 1H), 5.35 (m, 1H), 4.99 (m, 1H), 4.81 (br, 1H), 4.79 (br, 1H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.64 (br, 1H), 1.40 (br, 1H), 1.38 (d, 6H), 1.31 (m, 3H), 0.99 (m, 3H)

[0293] Example 197: (S)-Quinuclidin-3-yl (5-(3-(2-fluoroethoxy)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.42 (m, 1H), 7.34 (m, 1H), 7.27 (m, 1H), 7.19 (d, 1H), 7.14 (s, 1H), 6.91 (d, 1H), 5.00 (m, 1H), 4.96 (m, 3H), 4.79 (m, 1H), 4.33 (m, 1H), 4.25 (m, 1H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.31 (m, 3H), 1.00 (m, 3H)

[0294] Example 198: (S)-Quinuclidin-3-yl (5-(2-ethoxy-5-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.41 (m, 1H), 7.34 (s, 1H), 7.22 (m, 1H), 7.09 (s, 1H), 7.07 (d, 1H), 6.88 (d, 1H), 4.99 (m, 1H), 4.96 (m, 1H), 4.79 (m, 1H), 4.00 (m, 2H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.33 (s, 3H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.31 (m, 3H), 1.29 (m, 3H), 1.00 (m, 3H)

[0295] Example 199: (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(3-propoxyphenyl)-2,3-dihydro-1H-inden-1-yl) carbamate 11H-NMR (400 MHz, CDCl3) δ 7.44 (m, 1H), 7.35 (s, 1H), 7.31 (m, 2H), 7.15 (m, 1H), 7.11 (s, 1H), 6.88 (m, 1H), 5.00 (m, 1H), 4.96 (m, 1H), 4.79 (m, 1H), 4.01 (t, 2H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (m, 3H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 1.06 (t, 3H), 0.99 (m, 3H)

[0296] Example 200: (S)-Quinuclidin-3-yl (5-(2-methoxy-5-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.36 (m, 1H), 7.31 (s, 1H), 7.27 (m, 1H), 7.10 (m, 2H), 6.98 (d, 1H), 4.98 (m, 1H), 4.96 (m, 1H), 4.79 (m, 1H), 3.79 (s, 3H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.33 (s, 3H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0297] Example 201: (S)-Quinuclidin-3-yl (5-(2-butoxy-5-fluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 11H-NMR (400 MHz, CDCl3) δ 7.36 (m, 1H), 7.34 (s, 1H), 7.25 (m, 1H), 7.05 (m, 1H), 6.95 (m, 1H), 6.89 (m, 1H), 4.98 (m, 1H), 4.96 (m, 1H), 4.79 (m, 1H), 3.90 (t, 2H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (m, 3H), 1.60 (br, 1H), 1.40 (m, 3H), 1.30 (m, 3H), 0.99 (m, 3H), 0.91 (t, 3H)

[0298] Example 202: (S)-Quinuclidin-3-yl (5-(4-butoxy-3-chlorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.59 (s, 1H), 7.39 (m, 2H), 7.33 (s, 1H), 7.26 (m, 1H), 6.97 (d, 1H), 4.98 (m, 1H), 4.96 (m, 1H), 4.79 (m, 1H), 4.09 (t, 2H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (m, 3H), 1.70 (br, 1H), 1.60 (m, 3H), 1.40 (br, 3H), 1.30 (m, 3H), 0.99 (m, 3H), 0.97 (t, 3H)

[0299] Example 203: (S)-Quinuclidin-3-yl (5-(2,4-dipropoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 11H-NMR (400 MHz, CDCl3) δ 7.38 (m, 1H), 7.33 (s, 1H), 7.22 (m, 2H), 6.55 (s, 1H), 6.54 (m, 1H), 4.98 (m, 1H), 4.96 (m, 1H), 4.79 (m, 1H), 3.95 (m, 2H), 3.91 (m, 2H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (m, 3H), 1.70 (m, 3H), 1.60 (br, 1H), 1.40 (br, 3H), 1.30 (m, 3H), 1.05 (t, 3H), 0.99 (m, 6H)

[0300] Example 204: (S)-Quinuclidin-3-yl (5-(3-chloro-4-ethoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.60 (s, 1H), 7.41 (m, 2H), 7.33 (s, 1H), 7.26 (m, 1H), 6.97 (d, 1H), 4.99 (m, 1H), 4.96 (m, 1H), 4.79 (m, 1H), 4.15 (m, 2H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.50 (t, 3H), 1.40 (br, 3H), 1.30 (m, 3H), 0.99 (m, 3H)

[0301] Example 205: (S)-Quinuclidin-3-yl (5-(3-isobutoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 11H-NMR (400 MHz, CDCl3) δ 7.44 (m, 1H), 7.39 (s, 1H), 7.31 - 7.26 (m, 2H), 7.14 (d, 1H), 7.11 (s, 1H), 6.87 (d, 1H), 4.99 (m, 1H), 4.96 (m, 1H), 4.79 (m, 1H), 3.78 (d, 2H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.10 (m, 2H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 3H), 1.30 (m, 3H), 1.06 (d, 6H), 0.99 (m, 3H)

[0302] Example 206: (S)-Quinuclidin-3-yl (5-(4-ethoxy-2-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.25 (m, 1H), 7.14 (m, 3H), 6.81 (s, 1H), 6.76 (d, 1H), 4.99 (m, 1H), 4.96 (m, 1H), 4.79 (m, 1H), 4.06 (m, 2H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.24 (s, 3H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.43 (m, 4H), 1.30 (m, 3H), 1.00 (m, 3H)

[0303] Example 207: (S)-Quinuclidin-3-yl (5-(3-chloro-4-propoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 11H-NMR (400 MHz, CDCl3) δ 7.59 (s, 1H), 7.38 (m, 3H), 7.25 (m, 1H), 6.97 (d, 1H), 4.99 (m, 1H), 4.96 (m, 1H), 4.79 (m, 1H), 4.05 (m, 2H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (m, 3H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 1.11 (t, 3H), 0.99 (m, 3H)

[0304] Example 208: (S)-Quinuclidin-3-yl (5-(5-fluoro-2-isopropoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.38 (m, 1H), 7.34 (s, 1H), 7.25 (m, 1H), 7.02 (d, 1H), 6.92 (m, 2H), 4.99 (m, 1H), 4.96 (m, 1H), 4.79 (m, 1H), 4.24 (m, 1H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 1.20 (d, 6H), 0.99 (m, 3H)

[0305] Example 209: (S)-Quinuclidin-3-yl (5-(3-fluoro-4-isopropoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 11H-NMR (400 MHz, CDCl3) δ 7.38 (m, 1H), 7.36 (s, 1H), 7.32 - 7.24 (m, 3H), 7.01 (t, 1H), 6.92 (m, 2H), 4.99 (m, 1H), 4.96 (m, 1H), 4.79 (m, 1H), 4.57 (m, 1H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.38 (d, 6H), 1.30 (m, 3H), 0.99 (m, 3H)

[0306] Example 210: (S)-Quinuclidin-3-yl (5-(5-chloro-2-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.36 (m, 1H), 7.27 (m, 4H), 6.90 (d, 1H), 4.99 (m, 1H), 4.96 (m, 1H), 4.79 (m, 1H), 3.80 (s, 3H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0307] Example 211: (S)-Quinuclidin-3-yl (5-(2-fluoro-5-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.37 (m, 2H), 7.29 (m, 1H), 7.20 (d, 1H), 7.07 (m, 1H), 7.00 (m, 1H), 4.99 (m, 1H), 4.96 (m, 1H), 4.79 (m, 1H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.36 (s, 3H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0308] Example 212: (S)-Quinuclidin-3-yl (5-(5-chloro-2-ethoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.38 (m, 1H), 7.31 - 7.25 (m, 3H), 7.21 (m, 1H), 6.88 (d, 1H), 4.99 (m, 1H), 4.96 (m, 1H), 4.79 (m, 1H), 4.00 (m, 1H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 6H), 0.99 (m, 3H)

[0309] Example 213: (S)-Quinuclidin-3-yl (5-(5-fluoro-2-propoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.37 (m, 1H), 7.34 (s, 1H), 7.25 (m, 1H), 7.03 (d, 1H), 6.93 (m, 1H), 6.88 (m, 1H), 5.00 (m, 1H), 4.96 (m, 1H), 4.79 (m, 1H), 3.88 (m, 1H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (m, 3H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.99 (m, 6H)

[0310] Example 214: (S)-Quinuclidin-3-yl (5-(2-fluoro-6-propoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 11H-NMR (400 MHz, CDCl3) δ 7.25 (m, 4H), 6.76 (m, 2H), 5.00 (m, 1H), 4.96 (m, 1H), 4.79 (m, 1H), 3.91 (m, 1H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (m, 3H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H), 0.91 (t, 3H)

[0311] Example 215: (S)-Quinuclidin-3-yl (5-(3-fluoro-4-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.40 (m, 1H), 7.36 (s, 1H), 7.25 (m, 4H), 5.00 (m, 1H), 4.96 (m, 1H), 4.79 (m, 1H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.31 (s, 3H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0312] Example 216: (S)-Quinuclidin-3-yl (5-(3-fluoro-4-propoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.38 (m, 1H), 7.33 (s, 1H), 7.25 (m, 3H), 7.01 (t, 1H), 5.00 (m, 1H), 4.96 (m, 1H), 4.79 (m, 1H), 4.05 (t, 2H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (m, 3H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 1.07 (t, 3H), 0.99 (m, 3H)

[0313] Example 217: (S)-Quinuclidin-3-yl (5-(5-chloro-2-isopropoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.38 (m, 1H), 7.31 (s, 1H), 7.28 (m, 1H), 7.20 (d, 2H), 6.89 (d, 1H), 5.00 (m, 1H), 4.96 (m, 1H), 4.79 (m, 1H), 4.36 (m, 1H), 3.25 (m, 1H), 2.91~2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 1.28 (d, 6H), 0.99 (m, 3H)

[0314] Example 218: (S)-Quinuclidin-3-yl (5-(3-butoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.44 (m, 1H), 7.34 (s, 1H), 7.32 (m, 2H), 7.15 (d, 1H), 7.10 (s, 1H), 6.87 (m, 1H), 5.00 (m, 1H), 4.96 (m, 1H), 4.79 (m, 1H), 4.03 (t, 2H), 3.25 (m, 1H), 2.91~2.73 (m, 7H), 2.10 (br, 1H), 1.85 (m, 3H), 1.70 (br, 1H), 1.60 (m, 3H), 1.40 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0315] Example 219: (S)-Quinuclidin-3-yl (5-(3-fluoro-5-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.41 (m, 1H), 7.36 (s, 1H), 7.27 (m, 1H), 7.16 (s, 1H), 7.05 (d, 1H), 6.85 (d, 1H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.41 (s, 3H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0316] Example 220: (S)-Quinuclidin-3-yl (5-(5-fluoro-2-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.27 (m, 1H), 7.25 (m, 1H), 7.18 (m, 1H), 7.13 (s, 1H), 6.96 (m, 1H), 6.92 (d, 1H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.21 (s, 3H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0317] Example 221: (S)-Quinuclidin-3-yl (5-(2-chloro-5-(trifluoromethyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.65 (m, 2H), 7.51 (m, 1H), 7.26 (m, 3H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0318] Example 222: (S)-Quinuclidin-3-yl (5-(3-fluoro-5-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.41 (m, 1H), 7.36 (s, 1H), 7.26 (m, 1H), 6.89 (m, 2H), 6.58 (d, 1H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.86 (s, 3H), 3.25 (m, 1H), 2.91~2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0319] Example 223: (S)-Quinuclidin-3-yl (5-(2-chloro-5-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.33 (d, 1H), 7.26 (m, 2H), 7.23 (s, 1H), 7.14 (s, 1H), 7.07 (d, 1H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.25 (m, 1H), 2.91~2.73 (m, 7H), 2.34 (s, 3H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0320] Example 224: (S)-Quinuclidin-3-yl (5-(3-methoxy-5-(trifluoromethyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.43 (m, 3H), 7.28 (m, 1H), 7.25 (s, 1H), 7.10 (s, 1H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.91 (s, 3H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.45 (t, 3H), 1.40 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0321] Example 225: (S)-Quinuclidin-3-yl (5-(2-chloro-4-fluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.29 (m, 2H), 2.22 (m, 3H), 7.02 (m, 1H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.31 (m, 3H), 0.99 (m, 3H)

[0322] Example 226: (S)-Quinuclidin-3-yl (5-(4-fluoro-3-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.37 (m, 2H), 7.28 (m, 1H), 7.13 (m, 2H), 7.08 (m, 1H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.96 (s, 3H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0323] Example 227: (S)-Quinuclidin-3-yl (5-(3,4-dimethylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.41 (m, 1H), 7.38 (m, 2H), 7.27 (m, 2H), 7.19 (d, 1H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.25 (m, 1H), 2.91~2.73 (m, 7H), 2.33 (s, 3H), 2.31 (s, 3H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0324] Example 228: (S)-Quinuclidin-3-yl (5-(4-fluoro-2-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.25 (m, 1H), 7.17~7.08 (m, 3H), 6.98~6.90 (m, 2H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.25 (m, 1H), 2.91~2.73 (m, 7H), 2.25 (s, 3H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0325] Example 229: (S)-Quinuclidin-3-yl (5-(2-fluoro-4-(trifluoromethyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 11H-NMR (400 MHz, CDCl3) δ 7.54 (m, 1H), 7.46 (m, 1H), 7.41 - 7.36 (m, 4H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0326] Example 230: (S)-Quinuclidin-3-yl (5-(2-fluoro-5-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.39 - 7.27 (m, 3H), 7.04 (t, 1H), 6.91 (m, 1H), 6.83 (m, 1H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.83 (s, 3H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0327] Example 231: (S)-Quinuclidin-3-yl (5-(2-fluoro-3-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.40 - 7.27 (m, 3H), 7.12 (t, 1H), 6.97 (m, 2H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.93 (s, 3H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0328] Example 232: (S)-Quinuclidin-3-yl (5-(5-isopropyl-2-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.40 (m, 1H), 7.36 (s, 1H), 7.27 (m, 1H), 7.18 (m, 2H), 6.91 (d, 1H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.80 (s, 3H), 3.25 (m, 1H), 2.91 (m, 1H), 2.90 - 2.75 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 1.26 (d, 6H), 0.99 (m, 3H)

[0329] Example 233: (S)-Quinuclidin-3-yl (5-(2-fluoro-4-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.36 - 7.27 (m, 4H), 6.98 (m, 2H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.39 (s, 3H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0330] Example 234: (S)-Quinuclidin-3-yl (5-(5-fluoro-2-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1H-NMR (400 MHz, CDCl3) δ 7.37 (m, 1H), 7.31 (s, 1H), 7.27 (m, 1H), 7.02 (m, 1H), 6.97 (m, 1H), 6.91 (d, 1H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.79 (s, 3H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0331] Example 235: (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(5-methylfuran-3-yl)-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.47 (m, 1H), 7.45 (s, 1H), 7.19 (m, 1H), 6.51 (s, 1H), 6.04 (s, 1H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.25 (m, 1H), 2.91 - 2.73 (m, 7H), 2.31 (s, 3H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0332] Example 236: (S)-Quinuclidin-3-yl (5-(3-fluoro-2-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.36 - 7.26 (m, 3H), 7.07 (m, 3H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.73 (s, 3H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.99 (m, 6H)

[0333] Example 237: (S)-Quinuclidin-3-yl (5-(2-chloro-3-fluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.30~7.23 (m, 4H), 7.13 (m, 2H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.25 (m, 1H), 2.91~2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.99 (m, 6H)

[0334] Example 238: (S)-Quinuclidin-3-yl (5-(benzo[b]thiophen-3-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.92 (m, 2H), 7.46~7.33 (m, 6H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.25 (m, 1H), 2.91~2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0335] Example 239: (S)-Quinuclidin-3-yl (5-(4-fluoro-2-propoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.35 (m, 1H), 7.30 (s, 1H), 7.25 (m, 2H), 6.70 (m, 2H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.91 (t, 2H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (m, 3H), 1.60 (br, 1H), 1.40 (br, 1H), 1.30 (m, 3H), 0.99 (m, 6H)

[0336] Example 240: (S)-Quinuclidin-3-yl (5-(3-(tert-butyl)-5-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.44 (m, 1H), 7.40 (s, 2H), 7.26 (m, 1H), 7.20 (s, 2H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.42 (s, 3H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (m, 3H), 1.60 (br, 1H), 1.40 (br, 1H), 1.37 (s, 9H), 1.30 (m, 3H), 0.99 (m, 6H)

[0337] Example 241: (S)-Quinuclidin-3-yl (5-(2-chloro-5-ethoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.34 (d, 1H), 7.28 (d, 2H), 7.23 (s, 1H), 6.85 (s, 1H), 6.81 (d, 1H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 4.00 (q, 2H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (m, 3H), 1.60 (br, 1H), 1.41 (m, 4H), 1.30 (m, 3H), 0.99 (m, 6H)

[0338] Example 242: (S)-Quinuclidin-3-yl (5-(4-chloro-3-fluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.44 (m, 1H), 7.37 (m, 3H), 7.28 (m, 2H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.41 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0339] Example 243: (S)-Quinuclidin-3-yl (5-(2-fluoro-3-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.38 (m, 2H), 7.35 - 7.23 (m, 2H), 7.14 (m, 1H), 7.08 (t, 1H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.34 (s, 3H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.41 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0340] Example 244: (S)-Quinuclidin-3-yl (5-(5-cyano-2-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 11H-NMR (400 MHz, CDCl3) δ 7.64 (d, 1H), 7.57 (s, 1H), 7.31 (m, 3H), 7.02 (d, 1H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.88 (s, 3H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.41 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0341] Example 245: (S)-Quinuclidin-3-yl (5-(3-ethoxy-5-(trifluoromethyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.43 (d, 1H), 7.38 (s, 2H), 7.30 (m, 2H), 7.09 (s, 1H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 4.13 (m, 2H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.41 (m, 3H), 1.30 (m, 3H), 0.99 (m, 3H)

[0342] Example 246: (S)-Quinuclidin-3-yl (5-(3-fluoro-5-(trifluoromethyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.61 (s, 1H), 7.45 (m, 2H), 7.32 (s, 1H), 7.30 - 7.27 (m, 2H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.41 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0343] Example 247: (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(3-methyl-4-(trifluoromethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.43(s, 1H), 7.38(m, 3H), 7.26(m, 3H), 4.99(m, 1H), 4.88(m, 1H), 4.80(m, 1H), 3.25(m, 1H), 2.91~2.74(m, 7H), 2.38(s, 3H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.60(br, 1H), 1.41(br, 1H), 1.30(m, 3H), 0.99(m, 3H)

[0344] Example 248: (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(3-(methylthio)-5-(trifluoromethyl)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.57(d, 2H), 7.38(m, 3H), 7.29(m, 1H), 4.99(m, 1H), 4.88(m, 1H), 4.80(m, 1H), 3.25(m, 1H), 2.91~2.74(m, 7H), 2.57(s, 3H), 2.10(br, 1H), 1.85(br, 1H), 1.70(br, 1H), 1.60(br, 1H), 1.41(br, 1H), 1.30(m, 3H), 0.99(m, 3H)

[0345] Example 249: (S)-Quinuclidin-3-yl (5-(3-fluoro-4-(trifluoromethoxy)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 11H-NMR (400 MHz, CDCl3) δ 7.41~7.27 (m, 6H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.25 (m, 1H), 2.91~2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.41 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0346] Example 250: (S)-Quinuclidin-3-yl (5-(2-ethoxy-4-(trifluoromethyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.40 (m, 2H), 7.33 (s, 1H), 7.26 (m, 2H), 7.17 (s, 1H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 4.10 (m, 2H), 3.25 (m, 1H), 2.91~2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.41 (m, 4H), 1.30 (m, 3H), 0.99 (m, 3H)

[0347] Example 251: (S)-Quinuclidin-3-yl (5-(2-methoxy-5-(trifluoromethyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.57 (d, 1H), 7.54 (s, 1H), 7.37 (m, 1H), 7.29 (s, 2H), 7.02 (d, 1H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.86 (s, 3H), 3.25 (m, 1H), 2.91~2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.41 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0348] Example 252: (S)-Quinuclidin-3-yl (5-(2,4-bis(trifluoromethyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 8.00 (s, 1H), 7.81 (d, 1H), 7.48 (d, 1H), 7.26 (m, 1H), 7.14 (m, 1H), 7.12 (s, 1H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.41 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0349] Example 253: (S)-Quinuclidin-3-yl (5-(3-chloro-2-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.36 (d, 1H), 7,26 (m, 1H), 7.17 - 7.08 (m, 4H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.25 (s, 3H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.41 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0350] Example 254: (S)-Quinuclidin-3-yl (5-(3-methoxy-4-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.44 (m, 1H), 7.40 (s, 1H), 7.26 (m, 1H), 7.18 (d, 1H), 7.06 (d, 1H), 7.02 (s, 1H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.90 (s, 3H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.41 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0351] Example 255: (S)-Quinuclidin-3-yl (5-(4-fluoro-3-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.38 - 7.29 (m, 4H), 7.26 (m, 1H), 7.03 (t, 1H), 7.02 (s, 1H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.34 (s, 3H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.41 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0352] Example 256: (S)-Quinuclidin-3-yl (5-(2-ethoxy-5-fluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.40 (m, 1H), 7.33 (s, 1H), 7.25 (m, 1H), 7.05 (m, 1H), 6.95 (m, 1H), 6.88 (m, 1H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.99 (m, 2H), 3.25 (m, 1H), 2.91 - 2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.41 (br, 1H), 1.30 (m, 6H), 0.99 (m, 3H)

[0353] Example 257: (S)-Quinuclidin-3-yl (5-(3-fluoro-5-propoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.37 (m, 1H), 7.35 (s, 1H), 7.27 (m, 1H), 7.02 (t, 1H), 6.92 (m, 1H), 6.81 (m, 1H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.93 (m, 2H), 3.25 (m, 1H), 2.91~2.74 (m, 7H), 2.10 (br, 1H), 1.85 (m, 3H), 1.70 (br, 1H), 1.59 (br, 1H), 1.41 (br, 1H), 1.30 (m, 3H), 1.05 (t, 3H), 0.99 (m, 3H)

[0354] Example 258: (S)-Quinuclidin-3-yl (5-(3,5-bis(trifluoromethyl)phenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.99 (s, 2H), 7.85 (s, 1H), 7.44 (m, 2H), 7.32 (m, 1H), 4.99 (m, 1H), 4.88 (m, 1H), 4.80 (m, 1H), 3.25 (m, 1H), 2.91~2.74 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.41 (br, 1H), 1.30 (m, 3H), 0.99 (m, 3H)

[0355] Example 259: (S)-Quinuclidin-3-yl (5-(3-chloro-4-methylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.56 (s, 1H), 7.36 (m, 3H), 7.28 (m, 2H), 4.96 (s, 2H), 4.80 (br, 1H), 3.25 (m, 1H), 2.89 - 2.73 (m, 7H), 2.39 (s, 3H), 2.05 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (br, 1H), 1.40 (br, 1H), 1.29 (m, 3H), 0.98 (m, 3H)

[0356] Example 260: (S)-Quinuclidin-3-yl (5-(2,5-dimethylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.25 (m, 1H), 7.16 (t, 3H), 7.06 (m, 2H), 4.96 (s, 2H), 4.80 (br, 1H), 3.25 (m, 1H), 2.89 - 2.73 (m, 7H), 2.34 (s, 3H), 2.20 (s, 3H), 2.05 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (br, 1H), 1.40 (br, 1H), 1.29 (m, 3H), 0.98 (m, 3H)

[0357] Example 261: (S)-Quinuclidin-3-yl (5-(3-chloro-4-fluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.60 (d, 1H), 7.42 (m, 1H), 7.35 (m, 3H), 7.19 (t, 1H), 4.96 (s, 2H), 4.80 (br, 1H), 3.25 (m, 1H), 2.89 - 2.73 (m, 7H), 2.05 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (br, 1H), 1.40 (br, 1H), 1.29 (m, 3H), 0.98 (m, 3H)

[0358] Example 262: (S)-Quinuclidin-3-yl (5-(6-ethoxypyridin-3-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 8.33 (s, 1H), 7.76 (d, 1H), 7.69 (m, 1H), 7.51 (m, 1H), 7.46 (m, 1H), 7.36 - 7.27 (m, 1H), 6.77 (d, 1H), 4.96 (s, 2H), 4.80 (br, 1H), 4.37 (m, 2H), 3.25 (m, 1H), 2.89 - 2.73 (m, 7H), 2.05 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (br, 1H), 1.39 (m, 4H), 1.29 (m, 3H), 0.98 (m, 3H)

[0359] Example 263: (S)-Quinuclidin-3-yl (5-(2-ethoxypyridin-4-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 8.17 (d, 1H), 7.46 (m, 2H), 7.30 (m, 1H), 7.06 (d, 1H), 6.91 (s, 1H), 4.97 (m, 2H), 4.80 (br, 1H), 4.38 (m, 2H), 3.24 (m, 1H), 2.89 - 2.73 (m, 7H), 2.05 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (br, 1H), 1.40 (m, 4H), 1.30 (m, 3H), 0.96 (m, 3H)

[0360] Example 264: (S)-Quinuclidin-3-yl (5-(2-isopropoxypyridin-4-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 8.17 (d, 1H), 7.44 (m, 2H), 7.31 (m, 1H), 7.04 (d, 1H), 6.87 (s, 1H), 5.34 (m, 1H), 4.97 (s, 2H), 4.80 (br, 1H), 3.24 (m, 1H), 2.89 - 2.73 (m, 7H), 2.05 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (br, 1H), 1.40 (br, 1H), 1.36 (d, 6H), 1.28 (m, 3H), 0.97 (m, 3H)

[0361] Example 265: (S)-Quinuclidin-3-yl (2,2-dimethyl-5-(6-propoxypyridin-3-yl)-2,3-dihydro- IH -inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 8.34 (s, 1H), 7.76 (d, 1H), 7.34 - 7.32 (m, 3H), 6.79 (d, 1H), 4.96 (m, 2H), 4.80 (br, 1H), 4.28 (m, 2H), 3.25 (m, 1H), 2.89 - 2.74 (m, 7H), 2.05 (br, 1H), 1.85 (br, 1H), 1.81 (m, 2H), 1.68 (br, 1H), 1.58 (br, 1H), 1.40 (br, 1H), 1.29 (m, 3H), 1.06 (t, 3H), 0.98 (m, 3H)

[0362] Example 266: (S)-Quinuclidin-3-yl (5-(6-butoxypyridin-3-yl)-2,2-dimethyl-2,3-dihydro- IH -inden-1-yl) carbamate 1H-NMR (400 MHz, CDCl3) δ 8.33 (s, 1H), 7.76 (d, 1H), 7.34 - 7.31 (m, 3H), 6.78 (d, 1H), 4.96 (s, 2H), 4.80 (br, 1H), 4.31 (m, 2H), 3.25 (m, 1H), 2.89 - 2.73 (m, 7H), 2.05 (br, 1H), 1.85 (br, 1H), 1.78 (m, 2H), 1.68 (br, 1H), 1.58 (br, 1H), 1.48 (m, 2H), 1.40 (br, 1H), 1.29 (m, 3H), 1.06 (t, 3H), 0.98 (m, 6H)

[0363] Example 267: (S)-Quinuclidin-3-yl (5-(6-(2-methoxyethoxy)pyridin-3-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 8.32 (s, 1H), 7.76 (d, 1H), 7.36 - 7.28 (m, 3H), 6.86 (d, 1H), 4.96 (m, 2H), 4.80 (br, 1H), 4.51 (m, 2H), 3.78 (m, 2H), 3.45 (s, 3H), 3.25 (m, 1H), 2.89 - 2.73 (m, 7H), 2.05 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (br, 1H), 1.40 (br, 1H), 1.29 (m, 3H), 0.98 (m, 3H)

[0364] Example 268: (S)-Quinuclidin-3-yl (5-(6-isobutoxypyridin-3-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 11H-NMR (400 MHz, CDCl3) δ 8.34 (s, 1H), 7.76 (d, 1H), 7.35 - 7.27 (m, 3H), 6.80 (d, 1H), 4.96 (m, 2H), 4.78 (br, 1H), 4.10 (m, 2H), 3.27 (m, 1H), 2.89 - 2.74 (m, 7H), 2.08 (br, 1H), 1.86 (br, 1H), 1.69 (br, 1H), 1.58 (br, 1H), 1.42 (br, 1H), 1.29 (m, 3H), 1.00 (d, 6H), 0.98 (m, 3H)

[0365] Example 269: (S)-Quinuclidin-3-yl (5-(3-isobutylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.45 - 7.27 (m, 6H), 7.12 (d, 1H), 4.97 (m, 2H), 4.80 (br, 1H), 3.27 (m, 1H), 2.89 - 2.74 (m, 7H), 2.53 (d, 2H), 2.08 (br, 1H), 1.86 (br, 1H), 1.69 (br, 1H), 1.58 (br, 1H), 1.42 (br, 1H), 1.29 (m, 3H), 0.98 (m, 3H), 0.93 (d, 6H)

[0366] Example 270: (S)-Quinuclidin-3-yl (5-(4-butoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.50 (d, 2H), 7.39 (m, 2H), 7.28 (m, 1H), 6.96 (d, 2H), 4.97 (m, 2H), 4.80 (br, 1H), 4.02 (m, 1H), 3.27 (m, 1H), 2.89 - 2.74 (m, 7H), 2.53 (d, 2H), 2.08 (br, 1H), 1.86 (br, 1H), 1.77 (m, 2H), 1.69 (br, 1H), 1.58 (br, 1H), 1.52 (m, 2H), 1.42 (br, 1H), 1.29 (m, 3H), 0.98 (m, 6H)

[0367] Example 271: (S)-Quinuclidin-3-yl (5-(2,4-dimethoxypyridin-3-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.56 (d, 1H), 7.38 (m, 1H), 7.30 (s, 1H), 7.28 (m, 1H), 6.38 (d, 1H), 4.97 (m, 2H), 4.80 (br, 1H), 3.96 (s, 6H), 3.27 (m, 1H), 2.89 - 2.74 (m, 7H), 2.08 (br, 1H), 1.86 (br, 1H), 1.69 (br, 1H), 1.58 (br, 1H), 1.42 (br, 1H), 1.28 (m, 3H), 0.97 (m, 3H)

[0368] Example 272: (S)-Quinuclidin-3-yl (5-(2-acetylthiophen-3-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.53 (d, 1H), 7.30 - 7.19 (m, 3H), 7.03 (d, 1H), 5.02 (m, 1H), 4.94 (m, 1H), 4.79 (br, 1H), 3.28 (m, 1H), 2.89 - 2.72 (m, 7H), 2.16 (s, 3H), 2.08 (br, 1H), 1.86 (br, 1H), 1.69 (br, 1H), 1.58 (br, 1H), 1.42 (br, 1H), 1.30 (m, 3H), 0.97 (m, 3H)

[0369] Example 273: (S)-Quinuclidin-3-yl (5-((E)-3-fluorostyryl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.35~7.19 (m, 6H), 7.06 (d, 2H), 6.97 (m, 1H), 4.94 (m, 2H), 4.79 (br, 1H), 3.28 (m, 1H), 2.89~2.71 (m, 7H), 2.08 (br, 1H), 1.86 (br, 1H), 1.69 (br, 1H), 1.58 (br, 1H), 1.42 (br, 1H), 1.29 (m, 3H), 0.96 (m, 3H)

[0370] Example 274: (S)-Quinuclidin-3-yl (5-((E)-4-ethylstyryl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.44 (d, 2H), 7.34 (s, 1H), 7.21 (m, 4H), 7.07 (s, 2H), 4.94 (m, 2H), 4.79 (br, 1H), 3.28 (m, 1H), 2.89~2.71 (m, 7H), 2.63 (m, 2H), 2.08 (br, 1H), 1.86 (br, 1H), 1.69 (br, 1H), 1.58 (br, 1H), 1.42 (br, 1H), 1.27 (m, 6H), 0.94 (m, 3H)

[0371] Example 275: (S)-Quinuclidin-3-yl (5-((E)-2-cyclohexylvinyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.18~7.12 (m, 3H), 6.35 (m, 1H), 6.16 (m, 1H), 4.94 (m, 2H), 4.79 (br, 1H), 3.28 (m, 1H), 2.89~2.71 (m, 7H), 2.08 (br, 1H), 1.86 (br, 1H), 1.76 (m, 5H), 1.69 (br, 2H), 1.58 (br, 1H), 1.42 (br, 1H), 1.27 (m, 3H), 1.15 (m, 3H), 0.94 (m, 3H)

[0372] Examples 276 to 311 The title compounds of Examples 276 to 311 were prepared according to the same procedure as in Example 1 using (S)-quinuclidin-3-yl (5-bromo-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate prepared in Preparation Example 5 and the corresponding substituted boronic acids, respectively.

[0373] Example 276: (S)-Quinuclidin-3-yl (2,2-diethyl-5-(4-fluorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400MHz, CDCl3) δ 7.52(m, 2H), 7.50~7.27(m, 3H), 7.11(t, 2H), 5.13(m, 1H), 4.90(m, 1H), 4.78(m, 1H), 3.26(m, 1H), 2.87~2. 73(m, 7H), 2.11(br, 1H), 1.88(br, 1H), 1.61(br, 1H), 1.58(m, 3H), 1.37(br, 1H), 0.95(m, 3H), 0.85(m, 3H)

[0374] Example 277: (S)-Quinuclidin-3-yl (2,2-diethyl-5-(4-ethylphenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400MHz, CDCl3) δ 7.49(d, 2H), 7.40(m, 1H), 7.25(m, 3H), 5.12(m, 1H), 4.93(m, 1H), 4.78(m, 1H), 3.26(m, 1H), 2.87~2.69(m, 7H), 2.67 (m, 2H), 2.11(br, 1H), 1.88(br, 1H), 1.61(br, 1H), 1.58(m, 3H), 1.37(br, 1H), 1.26(t, 3H), 0.95(m, 3H), 0.86(m, 3H)

[0375] Example 278: (S)-Quinuclidin-3-yl (2,2-diethyl-5-(4-propylphenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.48 (d, 2H), 7.40 (m, 1H), 7.27 (m, 1H), 7.25 (d, 2H), 5.11 (m, 1H), 4.96 (m, 1H), 4.78 (m, 1H), 3.26 (m, 1H), 2.87 - 2.72 (m, 7H), 2.62 (m, 2H), 2.11 (br, 1H), 1.88 (br, 1H), 1.69 (m, 3H), 1.58 (m, 3H), 1.37 (br, 1H), 0.97 (m, 6H), 0.85 (m, 3H)

[0376] Example 279: (S)-Quinuclidin-3-yl (5-(4-(tert-butyl)phenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.51 (d, 2H), 7.45 (d, 3H), 7.37 (m, 1H), 7.27 (m, 1H), 5.12 (m, 1H), 4.94 (m, 1H), 4.78 (m, 1H), 3.26 (m, 1H), 2.87 - 2.71 (m, 7H), 2.11 (br, 1H), 1.88 (br, 1H), 1.69 (br, 1H), 1.58 (m, 3H), 1.38 (br, 1H), 1.36 (s, 9H), 0.97 (m, 6H), 0.86 (m, 3H)

[0377] Example 280: (S)-Quinuclidin-3-yl (5-(4-butylphenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.48 (d, 2H), 7.42 (m, 2H), 7.30 (m, 1H), 7.26 (d, 2H), 5.11 (m, 1H), 4.94 (m, 1H), 4.78 (m, 1H), 3.26 (m, 1H), 2.87 - 2.71 (m, 7H), 2.63 (m, 2H), 2.11 (br, 1H), 1.85 (br, 1H), 1.69 - 1.57 (m, 6H), 1.38 (m, 3H), 0.94 (m, 6H), 0.87 (m, 3H)

[0378] Example 281: (S)-Quinuclidin-3-yl (5-(4-cyclopropylphenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.46 (d, 2H), 7.40 (m, 1H), 7.30 (m, 1H), 7.28 (m, 1H), 7.14 (d, 2H), 5.12 (m, 1H), 4.94 (m, 1H), 4.78 (m, 1H), 3.26 (m, 1H), 2.87~2.71 (m, 7H), 2.11 (br, 1H), 1.94 (m, 1H), 1.85 (br, 1H), 1.60 (br, 1H), 1.58 (m, 3H), 1.37 (br, 1H), 0.95 (m, 5H), 0.87 (m, 3H), 0.74 (m, 2H)

[0379] Example 282: (S)-Quinuclidin-3-yl (2,2-diethyl-5-(4-isopropylphenyl)-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.50 (d, 2H), 7.41 (m, 1H), 7.30 (m, 1H), 7.28 (m, 3H), 5.11 (m, 1H), 4.95 (m, 1H), 4.78 (m, 1H), 3.26 (m, 1H), 2.94 (m, 1H), 2.88~2.73 (m, 7H), 2.11 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (m, 3H), 1.37 (br, 1H), 1.29 (d, 6H), 0.98 (m, 3H), 0.87 (m, 3H)

[0380] Example 283: (S)-Quinuclidin-3-yl (2,2-diethyl-5-(4-methoxyphenyl)-2,3-dihydro-1H-inden-1-yl) carbamate 1H-NMR (400 MHz, CDCl3) δ 7.50 (d, 2H), 7.38 (m, 1H), 7.30 (m, 2H), 6.96 (d, 2H), 5.12 (m, 1H), 4.91 (m, 1H), 4.88 (m, 1H), 3.85 (s, 3H), 3.26 (m, 1H), 2.88 - 2.71 (m, 7H), 2.11 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (m, 3H), 1.37 (br, 1H), 0.97 (m, 3H), 0.87 (m, 3H)

[0381] Example 284: (S)-Quinuclidin-3-yl (5-(4-ethoxyphenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.49 (d, 2H), 7.35 (m, 1H), 7.28 (m, 2H), 6.95 (d, 2H), 5.12 (m, 1H), 4.91 (m, 1H), 4.88 (m, 1H), 4.10 (m, 2H), 3.26 (m, 1H), 2.88 - 2.71 (m, 7H), 2.11 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (m, 3H), 1.41 (t, 3H), 1.37 (br, 1H), 0.97 (m, 3H), 0.87 (m, 3H)

[0382] Example 285: (S)-Quinuclidin-3-yl (2,2-diethyl-5-(4-propoxyphenyl)-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.49 (d, 2H), 7.35 (m, 1H), 7.28 (m, 2H), 6.96 (d, 2H), 5.12 (m, 1H), 4.91 (m, 1H), 4.88 (m, 1H), 3.98 (t, 2H), 3.26 (m, 1H), 2.88 - 2.71 (m, 7H), 2.11 (br, 1H), 1.85 (m, 3H), 1.68 (br, 1H), 1.58 (m, 3H), 1.37 (br, 1H), 1.06 (t, 3H), 0.97 (m, 3H), 0.87 (m, 3H)

[0383] Example 286: (S)-Quinuclidin-3-yl (2,2-diethyl-5-(4-isopropoxyphenyl)-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.49 (d, 2H), 7.35 (m, 1H), 7.28 (m, 2H), 6.96 (d, 2H), 5.12 (m, 1H), 4.91 (m, 1H), 4.78 (m, 1H), 4.77 (m, 1H), 3.26 (m, 1H), 2.88 - 2.71 (m, 7H), 2.11 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (m, 3H), 1.37 (br, 1H), 1.36 (d, 6H), 0.96 (m, 3H), 0.87 (m, 3H)

[0384] Example 287: (S)-Quinuclidin-3-yl (2,2-diethyl-5-(4-isobutylphenyl)-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.48 (d, 2H), 7.38 (m, 1H), 7.28 (m, 2H), 7.20 (d, 2H), 5.13 (m, 1H), 4.92 (m, 1H), 4.78 (m, 1H), 3.26 (m, 1H), 2.88 - 2.73 (m, 7H), 2.51 (d, 2H), 2.11 (br, 1H), 1.92 (m, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (m, 3H), 1.37 (br, 1H), 0.96 (m, 3H), 0.93 (d, 6H), 0.86 (m, 3H)

[0385] Example 288: (S)-Quinuclidin-3-yl (2,2-diethyl-5-(3-fluorophenyl)-2,3-dihydro-1H-inden-1-yl) carbamate 1H-NMR (400 MHz, CDCl3) δ 7.41~7.02 (m, 6H), 7.02 (t, 1H), 5.14 (m, 1H), 4.92 (m, 1H), 4.79 (m, 1H), 3.24 (m, 1H), 2.88~2.74 (m, 7H), 2.11 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (m, 3H), 1.37 (br, 1H), 0.96 (m, 3H), 0.86 (m, 3H)

[0386] Example 289: (S)-Quinuclidin-3-yl (2,2-diethyl-5-(3-methoxyphenyl)-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.43 (m, 1H), 7.37~7.27 (m, 3H), 7.17 (d, 1H), 7.15 (s, 1H), 6.88 (d, 1H), 5.13 (m, 1H), 4.91 (m, 1H), 4.79 (m, 1H), 3.87 (s, 3H), 3.25 (m, 1H), 2.88~2.74 (m, 7H), 2.05 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (m, 3H), 1.37 (br, 1H), 0.96 (m, 3H), 0.86 (m, 3H)

[0387] Example 290: (S)-Quinuclidin-3-yl (5-(3-ethoxyphenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.41 (m, 1H), 7.38~7.27 (m, 3H), 7.15 (d, 1H), 7.13 (s, 1H), 6.89 (d, 1H), 5.13 (m, 1H), 4.91 (m, 1H), 4.79 (m, 1H), 4.12 (m, 2H), 3.25 (m, 1H), 2.88~2.74 (m, 7H), 2.05 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (m, 3H), 1.43 (t, 3H), 1.37 (br, 1H), 0.96 (m, 3H), 0.87 (m, 3H)

[0388] Example 291: (S)-Quinuclidin-3-yl (2,2-diethyl-5-(3-isopropoxyphenyl)-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.41 (m, 1H), 7.39 - 7.27 (m, 3H), 7.12 (d, 1H), 7.09 (s, 1H), 6.88 (d, 1H), 5.13 (m, 1H), 4.91 (m, 1H), 4.78 (m, 1H), 4.62 (m, 1H), 3.25 (m, 1H), 2.88 - 2.73 (m, 7H), 2.05 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (m, 3H), 1.29 (br, 1H), 1.26 (d, 6H), 0.97 (m, 3H), 0.86 (m, 3H)

[0389] Example 292: (S)-Quinuclidin-3-yl (2,2-diethyl-5-(3-ethylphenyl)-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.44 - 7.27 (m, 6H), 7.18 (d, 1H), 5.13 (m, 1H), 4.93 (m, 1H), 4.78 (m, 1H), 3.27 (m, 1H), 2.85 - 2.71 (m, 7H), 2.68 (m, 2H), 2.05 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (m, 3H), 1.39 (br, 1H), 1.29 (t, 3H), 0.97 (m, 3H), 0.86 (m, 3H)

[0390] Example 293: (S)-Quinuclidin-3-yl (2,2-diethyl-5-(3-isopropylphenyl)-2,3-dihydro-1H-inden-1-yl) carbamate 11H-NMR (400 MHz, CDCl3) δ 7.44~7.27 (m, 6H), 7.21 (d, 1H), 5.14 (m, 1H), 4.92 (m, 1H), 4.79 (m, 1H), 3.27 (m, 1H), 2.99 (m, 1H), 2.85~2.71 (m, 7H), 2.05 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (m, 3H), 1.39 (br, 1H), 1.27 (d, 6H), 0.98 (m, 3H), 0.86 (m, 3H)

[0391] Example 294: (S)-Quinuclidin-3-yl (5-(3-(tert-butyl)phenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.58 (s, 1H), 7.41~7.27 (m, 6H), 5.11 (m, 1H), 4.9 (m, 1H), 4.79 (m, 1H), 3.27 (m, 1H), 2.86~2.75 (m, 7H), 2.05 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (m, 3H), 1.39 (br, 1H), 1.38 (s, 9H), 0.96 (m, 3H), 0.87 (m, 3H)

[0392] Example 295: (S)-Quinuclidin-3-yl (5-(2,3-dimethoxyphenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.37~7.26 (m, 3H), 7.10 (m, 1H), 6.92 (d, 2H), 5.14 (m, 1H), 4.92 (m, 1H), 4.77 (m, 1H), 3. (s, 3H), 3.59 (s, 3H), 3.25 (m, 1H), 2.86~2.73 (m, 7H), 2.05 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (m, 3H), 1.37 (br, 1H), 0.96 (m, 3H), 0.85 (m, 3H)

[0393] Example 296: (S)-Quinuclidin-3-yl (5-(2,4-dimethoxyphenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.33 (m, 1H), 7.28 - 7.21 (m, 3H), 6.57 (m, 2H), 5.11 (m, 1H), 4.90 (m, 1H), 4.85 (m, 1H), 3.85 (s, 3H), 3.80 (s, 3H), 3.24 (m, 1H), 2.86 - 2.71 (m, 7H), 2.05 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (m, 3H), 1.37 (br, 1H), 0.95 (m, 3H), 0.87 (m, 3H)

[0394] Example 297: (S)-Quinuclidin-3-yl (5-(2,5-dimethoxyphenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.35 (m, 1H), 7.30 - 7.27 (m, 2H), 6.92 - 6.83 (m, 3H), 5.12 (m, 1H), 4.90 (m, 1H), 4.85 (m, 1H), 3.80 (s, 3H), 3.75 (s, 3H), 3.24 (m, 1H), 2.86 - 2.72 (m, 7H), 2.05 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (m, 3H), 1.37 (br, 1H), 0.96 (m, 3H), 0.87 (m, 3H)

[0395] Example 298: (S)-Quinuclidin-3-yl (5-(3,4-dimethoxyphenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1H-NMR (400 MHz, CDCl3) δ 7.39 (m, 1H), 7.31 (s, 1H), 7.28 (m, 1H), 7.13 (d, 1H), 7.08 (s, 1H), 6.93 (d, 1H), 5.12 (m, 1H), 4.91 (m, 1H), 4.85 (m, 1H), 3.95 (s, 3H), 3.92 (s, 3H), 3.24 (m, 1H), 2.86 - 2.72 (m, 7H), 2.05 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (m, 3H), 1.37 (br, 1H), 0.95 (m, 3H), 0.86 (m, 3H)

[0396] Example 299: (S)-Quinuclidin-3-yl (5-(3,5-dimethoxyphenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.40 (m, 1H), 7.39 (s, 1H), 7.29 (m, 1H), 6.70 (s, 2H), 6.45 (m, 1H), 5.13 (m, 1H), 4.92 (m, 1H), 4.85 (brs, 1H), 3.85 (s, 6H), 3.24 (m, 1H), 2.86 - 2.73 (m, 7H), 2.05 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (m, 3H), 1.37 (br, 1H), 0.96 (m, 3H), 0.87 (m, 3H)

[0397] Example 300: (S)-Quinuclidin-3-yl (5-(2,6-dimethoxyphenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.30 - 7.26 (m, 2H), 7.18 (d, 1H), 7.14 (s, 1H), 6.65 (d, 2H), 5.12 (m, 1H), 4.92 (m, 1H), 4.77 (m, 1H), 3.73 (s, 6H), 3.24 (m, 1H), 2.85 - 2.71 (m, 7H), 2.05 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (m, 3H), 1.37 (br, 1H), 0.96 (m, 3H), 0.88 (m, 3H)

[0398] Example 301: (S)-Quinuclidin-3-yl (5-(3-(difluoromethyl)phenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.70 (m, 2H), 7.53 - 7.39 (m, 4H), 7.31 (m, 1H), 6.85 - 6.56 (t, 1H), 5.15 (m, 1H), 4.92 (m, 1H), 4.79 (m, 1H), 3.24 (m, 1H), 2.85 - 2.74 (m, 7H), 2.05 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (m, 3H), 1.37 (br, 1H), 0.96 (m, 3H), 0.86 (m, 3H)

[0399] Example 302: (S)-Quinuclidin-3-yl (5-(3-(dimethylamino)phenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.43 (m, 1H), 7.38 (s, 1H), 7.27 (m, 2H), 6.91 (m, 2H), 6.73 (d, 1H), 5.13 (m, 1H), 4.88 (m, 1H), 4.79 (m, 1H), 3.24 (m, 1H), 3.00 (s, 6H), 2.85 - 2.74 (m, 7H), 2.05 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (m, 3H), 1.37 (br, 1H), 0.96 (m, 3H), 0.87 (m, 3H)

[0400] Example 303: (S)-Quinuclidin-3-yl (5-(4-ethoxy-3,5-dimethylphenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate 11H-NMR (400 MHz, CDCl3) δ 7.38 - 7.33 (m, 2H), 7.28 (m, 1H), 7.21 (s, 2H), 5.12 (m, 1H), 4.88 (m, 1H), 4.79 (m, 1H), 3.89 (q, 2H), 3.25 (m, 1H), 2.85 - 2.74 (m, 7H), 2.33 (s, 6H), 2.05 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (m, 3H), 1.41 (t, 3H), 1.37 (br, 1H), 0.95 (m, 3H), 0.85 (m, 3H)

[0401] Example 304: (S)-Quinuclidin-3-yl (5-(3,5-dimethyl-4-propoxyphenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.38 - 7.30 (m, 2H), 7.28 (m, 1H), 7.20 (s, 2H), 5.11 (m, 1H), 4.93 (m, 1H), 4.79 (m, 1H), 3.77 (t, 2H), 3.25 (m, 1H), 2.85 - 2.74 (m, 7H), 2.33 (s, 6H), 2.05 (br, 1H), 1.85 (m, 3H), 1.68 (br, 1H), 1.58 (m, 3H), 1.37 (br, 1H), 1.09 (t, 3H), 0.95 (m, 3H), 0.85 (m, 3H)

[0402] Example 305: (S)-Quinuclidin-3-yl (5-(4-butoxy-3,5-dimethylphenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.38 - 7.30 (m, 2H), 7.28 (m, 1H), 7.20 (s, 2H), 5.12 (m, 1H), 4.91 (m, 1H), 4.79 (m, 1H), 3.78 (t, 2H), 3.25 (m, 1H), 2.85 - 2.74 (m, 7H), 2.33 (s, 6H), 2.05 (br, 1H), 1.85 (m, 3H), 1.68 (br, 1H), 1.58 (m, 5H), 1.37 (br, 1H), 0.99 (t, 3H), 0.95 (m, 3H), 0.86 (m, 3H)

[0403] Example 306: (S)-Quinuclidin-3-yl (2,2-diethyl-5-(thiophen-3-yl)-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.45~7.36 (m, 5H), 7.26 (m, 1H), 5.11 (m, 1H), 4.88 (m, 1H), 4.77 (m, 1H), 3.25 (m, 1H), 2.85~2.72 (m, 7H), 2.05 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (m, 3H), 1.37 (br, 1H), 0.95 (m, 3H), 0.85 (m, 3H)

[0404] Example 307: (S)-Quinuclidin-3-yl (2,2-diethyl-5-(furan-3-yl)-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.70 (s, 1H), 7.46 (s, 1H), 7.30~7.20 (m, 3H), 6.68 (s, 1H), 5.10 (m, 1H), 4.88 (m, 1H), 4.78 (m, 1H), 3.25 (m, 1H), 2.85~2.69 (m, 7H), 2.05 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (m, 3H), 1.37 (br, 1H), 0.94 (m, 3H), 0.85 (m, 3H)

[0405] Example 308: (S)-Quinuclidin-3-yl (5-(6-(cyclopropylmethoxy)pyridin-3-yl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1H-NMR (400 MHz, CDCl3) δ 8.31 (s, 1H), 7.77 (d, 1H), 7.31 (m, 3H), 6.82 (d, 1H), 5.12 (m, 1H), 4.93 (m, 1H), 4.78 (m, 1H), 4.16 (m, 2H), 3.25 (m, 1H), 2.85 - 2.72 (m, 7H), 2.05 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (m, 3H), 1.37 (br, 1H), 0.94 (m, 3H), 0.85 (m, 3H), 0.63 (m, 2H), 0.37 (m, 2H)

[0406] Example 309: (S)-Quinuclidin-3-yl (5-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.33 - 7.24 (m, 5H), 7.10 (m, 1H), 5.14 (m, 1H), 4.91 (m, 1H), 4.87 (m, 1H), 3.25 (m, 1H), 2.85 - 2.73 (m, 7H), 2.05 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (m, 3H), 1.37 (br, 1H), 0.96 (m, 3H), 0.86 (m, 3H)

[0407] Example 310: (S)-Quinuclidin-3-yl (2,2-diethyl-5-(2-fluoro-4-methoxyphenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.34 - 7.27 (m, 4H), 6.74 (m, 2H), 5.12 (m, 1H), 4.94 (m, 1H), 4.77 (m, 1H), 3.83 (s, 3H), 3.25 (m, 1H), 2.85 - 2.72 (m, 7H), 2.05 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (m, 3H), 1.37 (br, 1H), 0.96 (m, 3H), 0.86 (m, 3H)

[0408] Example 311: (S)-Quinuclidin-3-yl (5-(3-chloro-4-isopropoxyphenyl)-2,2-diethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.59 (s, 1H), 7.40 - 7.01 (m, 4H), 7.00 (d, 1H), 5.13 (m, 1H), 4.94 (m, 1H), 4.77 (m, 1H), 3.83 (s, 3H), 3.25 (m, 1H), 2.85 - 2.72 (m, 7H), 2.05 (br, 1H), 1.85 (br, 1H), 1.68 (br, 1H), 1.58 (m, 3H), 1.37 (br, 1H), 0.96 (m, 3H), 0.86 (m, 3H)

[0409] Examples 312 - 348 Using (S)-quinuclidin-3-yl (5-bromo-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate prepared in Production Example 6 and the corresponding substituted boronic acid respectively, the title compounds of Examples 312 - 348 were produced according to the same procedure as in Example 1.

[0410] Example 312: (S)-Quinuclidin-3-yl (5-(4-ethylphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.42 (d, 2H), 7.24 (m, 3H), 6.85 (d, 1H), 4.94 (m, 1H), 4.82 (m, 1H), 4.74 (br, 1H), 3.79 (d, 3H), 3.29 (m, 1H), 2.91 (m, 2H), 2.89 - 2.70 (m, 5H), 2.69 (m, 2H), 2.11 (br, 1H), 1.88 (br, 1H), 1.72 (br, 1H), 1.61 (br, 1H), 1.44 (br, 1H), 1.30 (m, 6H), 1.00 (m, 3H)

[0411] Example 313: (S)-Quinuclidin-3-yl (6-methoxy-2,2-dimethyl-5-(4-propylphenyl)-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.41 (d, 2H), 7.22 (d, 2H), 7.11 (s, 1H), 6.85 (d, 1H), 4.95 (m, 1H), 4.82 (m, 1H), 4.74 (br, 1H), 3.79 (d, 3H), 3.29 (m, 1H), 2.90 (m, 2H), 2.89~2.71 (m, 5H), 2.62 (m, 2H), 2.11 (br, 1H), 1.88 (br, 1H), 1.72~1.67 (m, 3H), 1.61 (br, 1H), 1.43 (br, 1H), 1.32 (m, 3H), 1.00 (m, 6H)

[0412] Example 314: (S)-Quinuclidin-3-yl (5-(4-isopropylphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.43 (d, 2H), 7.26 (d, 2H), 7.11 (s, 1H), 6.85 (d, 1H), 4.95 (m, 1H), 4.82 (m, 1H), 4.74 (br, 1H), 3.80 (d, 3H), 3.29 (m, 1H), 2.92 (m, 3H), 2.89~2.71 (m, 5H), 2.11 (br, 1H), 1.88 (br, 1H), 1.71 (br, 1H), 1.62 (br, 1H), 1.44 (br, 1H), 1.30 (m, 9H), 1.00 (m, 3H)

[0413] Example 315: (S)-Quinuclidin-3-yl (5-(4-isobutylphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 11H-NMR (400 MHz, CDCl3) δ 7.41 (d, 2H), 7.17 (d, 2H), 7.11 (s, 1H), 6.85 (d, 1H), 4.95 (m, 1H), 4.82 (m, 1H), 4.74 (br, 1H), 3.80 (d, 3H), 3.29 (m, 1H), 2.90 - 2.71 (m, 7H), 2.50 (d, 2H), 2.11 (br, 1H), 1.92 (m, 2H), 1.71 (br, 1H), 1.62 (br, 1H), 1.44 (br, 1H), 1.30 (m, 3H), 1.00 (m, 3H), 0.99 (d, 6H)

[0414] Example 316: (S)-Quinuclidin-3-yl (5-(4-(tert-butyl)phenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.46 (m, 4H), 7.12 (s, 1H), 6.85 (d, 1H), 4.95 (m, 1H), 4.82 (m, 1H), 4.74 (br, 1H), 3.81 (d, 3H), 3.29 (m, 1H), 2.93 - 2.66 (m, 7H), 2.50 (d, 2H), 2.11 (br, 1H), 1.88 (br, 1H), 1.71 (br, 1H), 1.62 (br, 1H), 1.44 (br, 1H), 1.40 (s, 9H), 1.30 (m, 3H), 1.00 (m, 3H)

[0415] Example 317: (S)-Quinuclidin-3-yl (5-(4-cyclopropylphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 11H-NMR (400 MHz, CDCl3) δ 7.39 (d, 2H), 7.10 (d, 3H), 6.85 (d, 1H), 4.95 (m, 1H), 4.82 (m, 1H), 4.74 (br, 1H), 3.81 (d, 3H), 3.29 (m, 1H), 2.93 - 2.66 (m, 7H), 2.50 (d, 2H), 2.11 (br, 1H), 1.90 (m, 1H), 1.88 (br, 1H), 1.71 (br, 1H), 1.62 (br, 1H), 1.44 (br, 1H), 1.30 (m, 3H), 1.00 (m, 3H), 0.98 (d, 2H), 0.75 (m, 2H)

[0416] Example 318: (S)-Quinuclidin-3-yl (5-(4-ethoxyphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.42 (d, 2H), 7.09 (s, 1H), 6.93 (d, 2H), 6.81 (d, 1H), 4.94 (m, 2H), 4.81 (m, 1H), 4.09 (m, 2H), 3.80 (d, 3H), 3.28 (m, 1H), 2.90 - 2.671 (m, 7H), 2.11 (br, 1H), 1.90 (m, 1H), 1.88 (br, 1H), 1.71 (br, 1H), 1.62 (br, 1H), 1.43 (t, 4H), 1.26 (m, 3H), 0.97 (m, 3H)

[0417] Example 319: (S)-Quinuclidin-3-yl (6-methoxy-2,2-dimethyl-5-(4-propoxyphenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 11H-NMR (400 MHz, CDCl3) δ 7.42 (d, 2H), 7.09 (s, 1H), 6.94 (d, 2H), 6.82 (d, 1H), 4.94 (m, 2H), 4.81 (m, 1H), 3.95 (m, 2H), 3.80 (d, 3H), 3.28 (m, 1H), 2.90 - 2.67 (m, 7H), 2.11 (br, 1H), 1.90 (m, 1H), 1.88 (br, 1H), 1.83 (m, 2H), 1.71 (br, 1H), 1.62 (br, 1H), 1.43 (br, 1H), 1.26 (m, 3H), 1.07 (t, 3H), 0.97 (m, 3H)

[0418] Example 320: (S)-Quinuclidin-3-yl (5-(4-isopropoxyphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.42 (d, 2H), 7.09 (s, 1H), 6.90 (d, 2H), 6.85 (d, 1H), 4.93 (m, 2H), 4.81 (m, 1H), 4.59 (m, 1H), 3.80 (d, 3H), 3.28 (m, 1H), 2.90 - 2.72 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.43 (br, 1H), 1.37 (d, 6H), 1.28 (m, 3H), 0.97 (m, 3H)

[0419] Example 321: (S)-Quinuclidin-3-yl (5-(3,5-dimethyl-4-propoxyphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 11H-NMR (400 MHz, CDCl3) δ 7.13 (s, 2H), 7.07 (s, 1H), 6.82 (d, 1H), 4.93 (m, 2H), 4.81 (m, 1H), 3.78 (m, 5H), 3.27 (m, 1H), 2.90 - 2.69 (m, 7H), 2.31 (s, 6H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.69 (m, 2H), 1.60 (br, 1H), 1.43 (br, 1H), 1.28 (m, 3H), 1.09 (t, 3H), 0.93 (m, 3H)

[0420] Example 322: (S)-Quinuclidin-3-yl (5-(3-chloro-4-isopropoxyphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.52 (s, 1H), 7.33 (d, 1H), 7.07 (s, 1H), 6.96 (d, 1H), 6.83 (d, 1H), 4.93 (m, 2H), 4.81 (m, 1H), 4.58 (m, 1H), 3.78 (m, 3H), 3.27 (m, 1H), 2.90 - 2.70 (m, 7H), 2.10 (br, 1H), 1.86 (br, 1H), 1.71 (br, 1H), 1.60 (br, 1H), 1.43 (br, 1H), 1.40 (d, 6H), 1.28 (m, 3H), 0.96 (m, 3H)

[0421] Example 323: (S)-Quinuclidin-3-yl (5-(2-fluoro-4-methoxyphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1H-NMR (400 MHz, CDCl3) δ 7.24 (m, 1H), 7.03 (s, 1H), 6.87 (d, 1H), 6.75 - 6.67 (m, 2H), 4.96 (m, 2H), 4.81 (m, 1H), 3.80 (s, 3H), 3.78 (m, 3H), 3.27 (m, 1H), 2.90 - 2.70 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.58 (br, 1H), 1.41 (br, 1H), 1.28 (m, 3H), 0.97 (m, 3H)

[0422] Example 324: (S)-Quinuclidin-3-yl (5-(4-butoxyphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.42 (d, 2H), 7.09 (s, 1H), 6.93 (d, 2H), 6.83 (d, 1H), 4.93 (m, 2H), 4.81 (m, 1H), 3.98 (m, 2H), 3.79 (m, 3H), 3.27 (m, 1H), 2.90 - 2.71 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.71 (m, 2H), 1.69 (br, 1H), 1.59 (br, 1H), 1.52 (m, 2H), 1.43 (br, 1H), 1.27 (m, 3H), 0.99 (m, 6H)

[0423] Example 325: (S)-Quinuclidin-3-yl (5-(4-isobutylphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.42 (d, 2H), 7.09 (s, 1H), 6.93 (d, 2H), 6.83 (d, 1H), 4.93 (m, 2H), 4.81 (m, 1H), 3.79 (m, 5H), 3.27 (m, 1H), 2.90 - 2.71 (m, 7H), 2.10 (m, 2H), 1.85 (br, 1H), 1.69 (br, 1H), 1.59 (br, 1H), 1.43 (br, 1H), 1.27 (m, 3H), 0.99 (m, 6H)

[0424] Example 326: (S)-Quinuclidin-3-yl (5-(6-(Cyclopropylmethoxy)pyridin-3-yl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 8.24 (s, 1H), 7.74 (d, 1H), 7.07 (s, 1H), 6.86 (d, 1H), 6.80 (d, 1H), 4.93 (m, 2H), 4.81 (m, 1H), 4.15 (m, 2H), 3.79 (m, 3H), 3.27 (m, 1H), 2.90 - 2.71 (m, 7H), 2.10 (m, 1H), 1.85 (br, 1H), 1.69 (br, 1H), 1.59 (br, 1H), 1.43 (br, 1H), 1.27 (m, 3H), 0.97 (m, 3H), 0.62 (m, 2H), 0.38 (m, 2H)

[0425] Example 327: (S)-Quinuclidin-3-yl (5-(5-Chloro-2-methoxyphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.25 (s, 1H) 7.19 (m, 1H), 7.00 (s, 1H), 6.89 - 6.82 (m, 2H), 4.93 (m, 2H), 4.81 (m, 1H), 3.79 (m, 6H), 3.29 (m, 1H), 2.92 - 2.65 (m, 7H), 2.10 (m, 1H), 1.85 (br, 1H), 1.69 (br, 1H), 1.59 (br, 1H), 1.43 (br, 1H), 1.29 (m, 3H), 0.98 (m, 3H)

[0426] Example 328: (S)-Quinuclidin-3-yl (5-(4-Butylphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.40 (d, 2H) 7.20 (d, 2H), 7.10 (s, 1H), 6.84 (d, 1H), 4.95 (s, 2H), 4.80 (br, 1H), 3.78 (d, 3H), 3.25 (m, 1H), 2.92~2.65 (m, 7H), 2.64 (m, 2H), 2.10 (m, 1H), 1.85 (br, 1H), 1.69 (br, 1H), 1.60 (m, 2H), 1.59 (br, 1H), 1.43 (m, 3H), 1.29 (m, 3H), 0.98 (m, 3H), 0.92 (t, 3H)

[0427] Example 329: (S)-Quinuclidin-3-yl (6-methoxy-5-(4-methoxy-3,5-dimethylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.14 (s, 2H) 7.07 (s, 1H), 6.82 (d, 1H), 4.94 (s, 2H), 4.80 (br, 1H), 3.78 (d, 3H), 3.76 (s, 3H), 3.25 (m, 1H), 2.92~2.65 (m, 7H), 2.32 (s, 6H), 2.10 (m, 1H), 1.85 (br, 1H), 1.69 (br, 1H), 1.58 (br, 1H), 1.40 (br, 1H), 1.28 (m, 3H), 0.98 (m, 3H)

[0428] Example 330: (S)-Quinuclidin-3-yl (5-(4-ethoxy-3,5-dimethylphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.14 (s, 2H) 7.07 (s, 1H), 6.83 (d, 1H), 4.94 (s, 2H), 4.80 (br, 1H), 3.89 (m, 2H), 3.78 (d, 3H), 3.25 (m, 1H), 2.92~2.65 (m, 7H), 2.31 (s, 6H), 2.10 (m, 1H), 1.85 (br, 1H), 1.69 (br, 1H), 1.59 (br, 1H), 1.43 (t, 4H), 1.28 (m, 3H), 0.98 (m, 3H)

[0429] Example 331: (S)-Quinuclidin-3-yl (5-(4-butoxy-3,5-dimethylphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.13 (s, 2H), 7.07 (s, 1H), 6.83 (d, 1H), 4.93 (m, 2H), 4.80 (br, 1H), 3.80 (m, 3H), 3.25 (m, 1H), 2.92 - 2.71 (m, 7H), 2.69 (m, 2H), 2.31 (s, 6H), 2.10 (m, 1H), 1.85 (br, 1H), 1.77 (m, 2H), 1.69 (br, 1H), 1.60 (m, 2H), 1.59 (m, 3H), 1.43 (br, 1H), 1.29 (m, 3H), 0.98 (m, 6H)

[0430] Example 332: (S)-Quinuclidin-3-yl (6-methoxy-5-(2-methoxypyridin-4-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 8.15 (d, 1H), 7.11 (s, 1H), 7.03 (d, 1H), 6.89 (s, 1H), 6.85 (d, 1H), 4.93 (m, 2H), 4.80 (br, 1H), 3.97 (s, 3H), 3.79 (d, 3H), 3.25 (m, 1H), 2.92 - 2.71 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.69 (br, 1H), 1.59 (br, 1H), 1.43 (br, 1H), 1.29 (m, 3H), 0.98 (m, 6H)

[0431] Example 333: (S)-Quinuclidin-3-yl (5-(3-fluorophenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.34 (m, 1H), 7.25 (m, 2H), 7.10 (s, 1H), 7.02 (m, 1H), 6.86 (m, 1H), 4.95 (s, 2H), 4.80 (br, 1H), 3.81 (m, 3H), 3.25 (m, 1H), 2.90 - 2.71 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.69 (br, 1H), 1.59 (br, 1H), 1.46 (br, 1H), 1.28 (m, 3H), 0.98 (m, 3H)

[0432] Example 334: (S)-Quinuclidin-3-yl (5-(3-ethylphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.33 (s, 3H), 7.17 (m, 1H), 7.16 (s, 1H), 6.86 (m, 1H), 4.95 (m, 2H), 4.80 (br, 1H), 3.80 (m, 3H), 3.25 (m, 1H), 2.90 - 2.80 (m, 7H), 2.70 (m, 2H), 2.10 (br, 1H), 1.85 (br, 1H), 1.69 (br, 1H), 1.59 (br, 1H), 1.46 (br, 1H), 1.28 (m, 6H), 0.98 (m, 3H)

[0433] Example 335: (S)-Quinuclidin-3-yl (5-(3-isobutylphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.32 - 7.27 (m, 3H), 7.11 (m, 2H), 6.85 (m, 1H), 4.95 (m, 2H), 4.80 (br, 1H), 3.79 (m, 3H), 3.25 (m, 1H), 2.90 - 2.72 (m, 7H), 2.53 (d, 2H), 2.10 (br, 1H), 1.90 (m, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.46 (br, 1H), 1.28 (m, 3H), 0.98 (m, 3H), 0.90 (d, 6H)

[0434] Example 336: (S)-Quinuclidin-3-yl (5-(3-isopropylphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.33 (m, 3H), 7.20 (m, 1H), 7.12 (s, 1H), 6.85 (m, 1H), 4.95 (m, 2H), 4.80 (br, 1H), 3.80 (m, 3H), 3.25 (m, 1H), 2.95 (m, 1H), 2.90 - 2.72 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.46 (br, 1H), 1.28 (m, 9H), 0.98 (m, 3H)

[0435] Example 337: (S)-Quinuclidin-3-yl (5-(3-(tert-butyl)phenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.52 (s, 1H), 7.33 (m, 3H), 7.12 (s, 1H), 6.86 (m, 1H), 4.95 (m, 2H), 4.80 (br, 1H), 3.80 (m, 3H), 3.25 (m, 1H), 2.90 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.46 (br, 1H), 1.37 (s, 9H), 1.28 (m, 3H), 0.98 (m, 3H)

[0436] Example 338: (S)-Quinuclidin-3-yl (6-methoxy-5-(3-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 11H-NMR (400 MHz, CDCl3) δ 7.31 (m, 1H), 7.11 - 7.06 (m, 3H), 6.87 (m, 2H), 4.95 (m, 2H), 4.80 (br, 1H), 3.84 (s, 3H), 3.80 (m, 3H), 3.25 (m, 1H), 2.90 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.46 (br, 1H), 1.28 (m, 3H), 0.98 (m, 3H)

[0437] Example 339: (S)-Quinuclidin-3-yl (5-(3-ethoxyphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.30 (m, 1H), 7.11 (s, 1H), 7.07 (m, 2H), 6.85 (m, 2H), 4.95 (m, 2H), 4.80 (br, 1H), 4.08 (m, 2H), 3.79 (m, 3H), 3.25 (m, 1H), 2.90 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.46 (br, 1H), 1.43 (t, 3H), 1.28 (m, 3H), 0.98 (m, 3H)

[0438] Example 340: (S)-Quinuclidin-3-yl (6-methoxy-2,2-dimethyl-5-(3-propoxyphenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.28 (m, 1H), 7.11 (s, 1H), 7.06 (m, 2H), 6.86 (m, 2H), 4.95 (m, 2H), 4.80 (br, 1H), 3.96 (m, 2H), 3.79 (m, 3H), 3.25 (m, 1H), 2.90 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.80 (m, 2H), 1.70 (br, 1H), 1.59 (br, 1H), 1.46 (br, 1H), 1.28 (m, 3H), 0.98 (m, 6H)

[0439] Example 341: (S)-Quinuclidin-3-yl (5-(3-isopropoxyphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.28 (m, 1H), 7.11 (s, 1H), 7.05 (m, 2H), 6.85 (d, 2H), 4.95 (m, 2H), 4.80 (br, 1H), 4.59 (m, 1H), 3.80 (m, 3H), 3.25 (m, 1H), 2.90 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.46 (br, 1H), 1.35 (d, 6H), 1.28 (m, 3H), 0.98 (m, 3H)

[0440] Example 342: (S)-Quinuclidin-3-yl (5-(3-butoxyphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.28 (m, 1H), 7.10 (s, 1H), 7.05 (m, 2H), 6.86 (d, 2H), 4.95 (m, 2H), 4.80 (br, 1H), 3.98 (m, 2H), 3.80 (m, 3H), 3.25 (m, 1H), 2.90 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.78 (m, 2H), 1.70 (br, 1H), 1.59 (br, 1H), 1.55 (m, 2H), 1.46 (br, 1H), 1.28 (m, 3H), 0.98 (m, 6H)

[0441] Example 343: (S)-Quinuclidin-3-yl (5-(3-isobutoxyphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 11H-NMR (400 MHz, CDCl3) δ 7.28 (m, 1H), 7.11 (s, 1H), 7.05 (m, 2H), 6.85 (d, 2H), 4.95 (m, 2H), 4.80 (br, 1H), 3.80 (m, 3H), 3.75 (d, 2H), 3.25 (m, 1H), 2.90 - 2.73 (m, 7H), 2.10 (m, 2H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.46 (br, 1H), 1.28 (m, 3H), 0.98 (m, 9H)

[0442] Example 344: (S)-Quinuclidin-3-yl (5-(2,5-dimethoxyphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.03 (s, 1H), 7.03 - 6.80 (m, 4H), 4.95 (s, 2H), 4.80 (br, 1H), 3.78 (m, 6H), 3.73 (s, 3H), 3.25 (m, 1H), 2.90 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.46 (br, 1H), 1.28 (m, 3H), 0.98 (m, 3H)

[0443] Example 345: (S)-Quinuclidin-3-yl (5-(3,5-dimethoxyphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.11 (s, 1H), 6.85 (m, 1H), 6.65 (s, 2H), 6.45 (s, 1H), 4.95 (s, 2H), 4.80 (br, 1H), 3.80 (m, 9H), 3.25 (m, 1H), 2.90 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.46 (br, 1H), 1.28 (m, 3H), 0.98 (m, 3H)

[0444] Example 346: (S)-Quinuclidin-3-yl (5-(2-chloro-4-methoxyphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.17 (d, 1H), 7.00 (s, 1H), 6.96 (s, 1H), 6.84 (m, 2H), 4.95 (s, 2H), 4.80 (br, 1H), 3.82 (s, 3H), 3.75 (m, 3H), 3.25 (m, 1H), 2.90~2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.46 (br, 1H), 1.28 (m, 3H), 0.98 (m, 3H)

[0445] Example 347: (S)-Quinuclidin-3-yl (5-(4-ethoxy-3-fluorophenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.30 (m 1H), 7.18 (d, 1H), 7.08 (s, 1H), 6.98 (t, 1H), 6.84 (d, 1H), 4.95 (s, 2H), 4.80 (br, 1H), 4.14 (m, 2H), 3.79 (m, 3H), 3.25 (m, 1H), 2.90~2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.47 (t, 3H), 1.45 (br, 1H), 1.28 (m, 3H), 0.98 (m, 3H)

[0446] Example 348: (S)-Quinuclidin-3-yl (5-(4-isopropoxy-3,5-dimethylphenyl)-6-methoxy-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 11H-NMR (400 MHz, CDCl3) δ 7.13 (s, 2H), 7.08 (s, 1H), 6.82 (d, 1H), 4.95 (s, 2H), 4.80 (br, 1H), 4.22 (m, 1H), 3.78 (m, 3H), 3.25 (m, 1H), 2.90 - 2.73 (m, 7H), 2.30 (s, 6H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.45 (br, 1H), 1.30 (d, 6H), 1.28 (m, 3H), 0.98 (m, 3H)

[0447] Examples 349 - 388 (S)-Quinuclidin-3-yl (5-bromo-6-fluoro-heryl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate prepared in Production Example 7; and the corresponding substituted boronic acid were each used to produce the title compounds of Examples 349 - 388 according to the same procedure as in Example 1.

[0448] Example 349: (S)-Quinuclidin-3-yl (5-(4-ethylphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.44 (d, 2H), 7.27 (d, 2H), 7.20 (d, 1H), 7.03 - 6.97 (m, 1H), 4.93 (m, 2H), 4.79 (br, 1H), 3.28 (m, 1H), 2.90 - 2.71 (m, 7H), 2.69 (m, 2H), 2.11 (br, 1H), 1.85 (br, 1H), 1.72 (br, 1H), 1.59 (br, 1H), 1.43 (br, 1H), 1.32 (m, 6H), 0.97 (m, 3H)

[0449] Example 350: (S)-Quinuclidin-3-yl (6-fluoro-2,2-dimethyl-5-(4-propylphenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 11H-NMR (400 MHz, CDCl3) δ 7.44 (d, 2H), 7.27 (m, 2H), 7.00 (m, 1H), 7.03 - 6.97 (m, 1H), 4.92 (m, 2H), 4.79 (br, 1H), 3.28 (m, 1H), 2.90 - 2.71 (m, 7H), 2.63 (m, 2H), 2.11 (br, 1H), 1.85 (br, 1H), 1.72 (br, 1H), 1.68 (m, 2H), 1.60 (br, 1H), 1.43 (br, 1H), 1.32 (m, 6H), 0.97 (m, 3H)

[0450] Example 351: (S)-Quinuclidin-3-yl (6-fluoro-5-(4-isopropylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.44 (d, 2H), 7.27 (m, 2H), 7.00 (m, 1H), 7.03 - 6.97 (m, 1H), 4.92 (m, 2H), 4.79 (br, 1H), 3.28 (m, 1H), 2.96 (m, 1H), 2.90 - 2.72 (m, 7H), 2.11 (br, 1H), 1.85 (br, 1H), 1.72 (br, 1H), 1.60 (br, 1H), 1.43 (br, 1H), 1.28 (m, 9H), 0.97 (m, 3H)

[0451] Example 352: (S)-Quinuclidin-3-yl (6-fluoro-5-(4-isobutylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.44 (d, 2H), 7.22 (d, 3H), 7.03 - 6.97 (m, 1H), 4.92 (m, 2H), 4.79 (br, 1H), 3.28 (m, 1H), 2.90 - 2.72 (m, 7H), 2.52 (d, 2H), 2.11 (br, 1H), 1.94 (m, 1H), 1.85 (br, 1H), 1.72 (br, 1H), 1.60 (br, 1H), 1.43 (br, 1H), 1.30 (m, 3H), 0.98 (m, 3H), 0.94 (d, 6H)

[0452] Example 353: (S)-Quinuclidin-3-yl (5-(4-(tert-butyl)phenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.46 (s, 4H), 7.21 (d, 1H), 7.03 - 6.97 (m, 1H), 4.99 - 4.90 (m, 2H), 4.79 (br, 1H), 3.29 (m, 1H), 2.90 - 2.69 (m, 7H), 2.11 (br, 1H), 1.94 (m, 1H), 1.85 (br, 1H), 1.72 (br, 1H), 1.60 (br, 1H), 1.43 (br, 1H), 1.33 (s, 9H), 1.30 (m, 3H), 0.98 (m, 3H)

[0453] Example 354: (S)-Quinuclidin-3-yl (5-(4-cyclopropylphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.42 (d, 2H), 7.20 (d, 1H), 7.13 (d, 2H), 7.02 - 6.99 (m, 1H), 4.98 - 4.88 (m, 2H), 4.79 (br, 1H), 3.28 (m, 1H), 2.88 - 2.68 (m, 7H), 2.11 (br, 1H), 1.95 (m, 1H), 1.85 (br, 1H), 1.72 (br, 1H), 1.60 (br, 1H), 1.43 (br, 1H), 1.29 (m, 3H), 1.00 (m, 2H), 0.98 (m, 3H), 0.75 (m, 2H)

[0454] Example 355: (S)-Quinuclidin-3-yl (6-fluoro-5-(4-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.46 (d, 2H), 7.19 (d, 1H), 6.99 (m, 3H), 4.98 (m, 1H), 4.88 (m, 1H), 4.79 (br, 1H), 3.96 (s, 3H), 3.28 (m, 1H), 2.88 - 2.68 (m, 7H), 2.11 (br, 1H), 1.85 (br, 1H), 1.72 (br, 1H), 1.60 (br, 1H), 1.43 (br, 1H), 1.29 (m, 3H), 0.98 (m, 3H)

[0455] Example 356: (S)-Quinuclidin-3-yl (5-(4-ethoxyphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.44 (d, 2H), 7.18 (d, 1H), 6.98 (m, 3H), 4.98 (m, 1H), 4.88 (m, 1H), 4.79 (br, 1H), 4.11 (m, 2H), 3.28 (m, 1H), 2.88 - 2.68 (m, 7H), 2.11 (br, 1H), 1.85 (br, 1H), 1.72 (br, 1H), 1.60 (br, 1H), 1.45 (t, 3H), 1.44 (br, 1H), 1.29 (m, 3H), 0.98 (m, 3H)

[0456] Example 357: (S)-Quinuclidin-3-yl (6-fluoro-2,2-dimethyl-5-(4-propoxyphenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.44 (d, 2H), 7.18 (d, 1H), 6.98 (m, 3H), 4.98 (m, 1H), 4.88 (m, 1H), 4.79 (br, 1H), 3.97 (t, 2H), 3.28 (m, 1H), 2.88 - 2.68 (m, 7H), 2.11 (br, 1H), 1.85 (m, 3H), 1.72 (br, 1H), 1.60 (br, 1H), 1.45 (t, 3H), 1.44 (br, 1H), 1.29 (m, 3H), 1.05 (t, 3H), 0.98 (m, 3H)

[0457] Example 358: (S)-Quinuclidin-3-yl (6-fluoro-5-(4-isopropoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.43 (d, 2H), 7.18 (d, 1H), 7.02 (m, 1H), 6.94 (d, 2H), 4.98 (m, 1H), 4.88 (m, 1H), 4.79 (br, 1H), 4.58 (m, 1H), 3.28 (m, 1H), 2.88~2.68 (m, 7H), 2.11 (br, 1H), 1.85 (br, 1H), 1.72 (br, 1H), 1.60 (br, 1H), 1.44 (br, 1H), 1.31 (d, 6H), 1.29 (m, 3H), 0.98 (m, 3H)

[0458] Example 359: (S)-Quinuclidin-3-yl (5-(3-chloro-4-isopropoxyphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.54 (s, 1H), 7.37 (d, 1H), 7.18 (d, 1H), 7.02 (m, 2H), 4.98 (m, 2H), 4.79 (br, 1H), 4.57 (m, 1H), 3.28 (m, 1H), 2.88~2.68 (m, 7H), 2.11 (br, 1H), 1.85 (br, 1H), 1.72 (br, 1H), 1.60 (br, 1H), 1.44 (br, 1H), 1.42 (d, 6H), 1.28 (m, 3H), 0.98 (m, 3H)

[0459] Example 360: (S)-Quinuclidin-3-yl (6-fluoro-5-(2-fluoro-4-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.28 (m, 1H), 7.14 (d, 1H), 7.00 (m, 1H), 6.75 (m, 2H), 4.98 (m, 2H), 4.79 (br, 1H), 3.84 (s, 3H), 3.28 (m, 1H), 2.88 - 2.68 (m, 7H), 2.11 (br, 1H), 1.85 (br, 1H), 1.72 (br, 1H), 1.60 (br, 1H), 1.43 (br, 1H), 1.29 (m, 3H), 0.98 (m, 3H)

[0460] Example 361: (S)-Quinuclidin-3-yl (5-(4-butoxyphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.44 (d, 12), 7.18 (d, 1H), 6.98 (m, 3H), 4.98 (m, 2H), 4.79 (br, 1H), 4.01 (t, 2H), 3.28 (m, 1H), 2.88 - 2.68 (m, 7H), 2.11 (br, 1H), 1.85 (br, 1H), 1.81 (m, 2H), 1.72 (br, 1H), 1.60 (br, 1H), 1.51 (m, 2H), 1.43 (br, 1H), 1.29 (m, 3H), 0.98 (m, 6H)

[0461] Example 362: (S)-Quinuclidin-3-yl (6-fluoro-5-(4-isobutoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.44 (d, 2H), 7.18 (d, 1H), 6.97 (m, 3H), 4.98 (m, 2H), 4.79 (br, 1H), 3.77 (d, 2H), 3.28 (m, 1H), 2.88 - 2.68 (m, 7H), 2.11 (m, 3H), 1.85 (br, 1H), 1.81 (m, 2H), 1.72 (br, 1H), 1.60 (br, 1H), 1.51 (m, 2H), 1.43 (br, 1H), 1.29 (m, 3H), 1.05 (d, 6H), 0.98 (m, 6H)

[0462] Example 363: (S)-Quinuclidin-3-yl (5-(6-(Cyclopropylmethoxy)pyridin-3-yl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 8.27 (s, 1H), 7.74 (d, 1H), 7.16 (d, 1H), 7.00 (m, 1H), 6.83 (d, 1H), 4.98 (m, 1H), 4.90 (m, 1H), 4.79 (br, 1H), 4.18 (d, 2H), 3.28 (m, 1H), 2.88~2.68 (m, 7H), 2.11 (br, 1H), 1.85 (br, 1H), 1.72 (br, 1H), 1.60 (br, 1H), 1.43 (br, 1H), 1.29 (m, 4H), 0.98 (m, 3H), 0.64 (m, 2H), 0.37 (m, 2H)

[0463] Example 364: (S)-Quinuclidin-3-yl (5-(5-Chloro-2-methoxyphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.31 (m, 2H), 7.09 (d, 1H), 6.97 (m, 1H), 6.89 (d, 1H), 4.98 (m, 1H), 4.90 (m, 1H), 4.79 (br, 1H), 3,78 (s, 3H), 3.28 (m, 1H), 2.88~2.68 (m, 7H), 2.11 (br, 1H), 1.85 (br, 1H), 1.72 (br, 1H), 1.60 (br, 1H), 1.43 (br, 1H), 1.29 (m, 4H), 0.98 (m, 3H), 0.64 (m, 2H), 0.37 (m, 2H)

[0464] Example 365: (S)-Quinuclidin-3-yl (5-(4-Butylphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.42 (d, 2H), 7.25 (m, 3H), 6.97 (m, 1H), 4.95 (s, 1H), 4.85 (m, 1H), 4.80 (br, 1H), 3.25 (m, 1H), 2.92 - 2.65 (m, 7H), 2.64 (m, 2H), 2.10 (m, 1H), 1.85 (br, 1H), 1.69 (br, 1H), 1.60 (m, 2H), 1.59 (br, 1H), 1.43 (m, 3H), 1.29 (m, 3H), 0.98 (m, 6H)

[0465] Example 366: (S)-Quinuclidin-3-yl (6-fluoro-5-(4-methoxy-3,5-dimethylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.17 (s, 4H), 7.98 (m, 1H), 4.95 (s, 1H), 4.85 (m, 1H), 4.80 (br, 1H), 3.77 (s, 3H), 3.25 (m, 1H), 2.92 - 2.65 (m, 7H), 2.34 (s, 6H), 2.10 (br, 1H), 1.85 (br, 1H), 1.69 (br, 1H), 1.58 (br, 1H), 1.40 (br, 1H), 1.28 (m, 3H), 0.98 (m, 3H)

[0466] Example 367: (S)-Quinuclidin-3-yl (5-(4-ethoxy-3,5-dimethylphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.17 (s, 4H), 6.98 (m, 1H), 4.95 (s, 1H), 4.85 (m, 1H), 4.80 (br, 1H), 3.88 (d, 3H), 3.25 (m, 1H), 2.92 - 2.65 (m, 7H), 2.32 (s, 6H), 2.10 (br, 1H), 1.85 (br, 1H), 1.69 (br, 1H), 1.59 (br, 1H), 1.44 (t, 4H), 1.28 (m, 3H), 0.98 (m, 3H)

[0467] Example 368: (S)-Quinuclidin-3-yl (5-(4-butoxy-3,5-dimethylphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ δ 7.18 (s, 4H), 6.98 (m, 1H), 4.95 (s, 1H), 4.85 (m, 1H), 4.80 (br, 1H), 3.80 (m, 2H), 3.25 (m, 1H), 2.92~2.71 (m, 7H), 2.31 (s, 6H), 2.10 (m, 1H), 1.85 (br, 1H), 1.77 (m, 2H), 1.69 (br, 1H), 1.60 (m, 2H), 1.59 (m, 3H), 1.43 (br, 1H), 1.29 (m, 3H), 0.98 (m, 6H)

[0468] Example 369: (S)-Quinuclidin-3-yl (6-fluoro-5-(2-methoxypyridin-4-yl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 8.19 (d, 1H), 7.23 (m, 1H), 7.03 (m, 1H), 6.89 (s, 1H), 4.95 (s, 1H), 4.85 (m, 1H), 4.80 (br, 1H), 3.97 (s, 3H), 3.25 (m, 1H), 2.92~2.71 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.69 (br, 1H), 1.59 (br, 1H), 1.43 (br, 1H), 1.29 (m, 3H), 0.98 (m, 3H)

[0469] Example 370: (S)-Quinuclidin-3-yl (6-fluoro-5-(3-fluorophenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.38 (m, 1H), 7.36 - 7.19 (m, 3H), 7.05 (m, 2H), 4.95 (s, 1H), 4.85 (m, 1H), 4.80 (br, 1H), 3.25 (m, 1H), 2.90 - 2.71 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.69 (br, 1H), 1.59 (br, 1H), 1.46 (br, 1H), 1.28 (m, 3H), 0.98 (m, 3H)

[0470] Example 371: (S)-Quinuclidin-3-yl (5-(3-ethylphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.34 (m, 3H), 7.20 (m, 2H), 7.00 (m, 1H), 4.95 (s, 1H), 4.85 (m, 1H), 4.80 (br, 1H), 3.25 (m, 1H), 2.90 - 2.70 (m, 7H), 2.68 (m, 2H), 2.10 (br, 1H), 1.85 (br, 1H), 1.69 (br, 1H), 1.59 (br, 1H), 1.46 (br, 1H), 1.28 (m, 6H), 0.98 (m, 3H)

[0471] Example 372: (S)-Quinuclidin-3-yl (6-fluoro-5-(3-isobutylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.34 (m, 2H), 7.27 (m, 1H), 7.21 (m, 1H), 7.15 (m, 1H), 6.99 (m, 1H), 4.95 (s, 1H), 4.85 (m, 1H), 4.80 (br, 1H), 3.25 (m, 1H), 2.90 - 2.72 (m, 7H), 2.52 (d, 2H), 2.10 (br, 1H), 1.90 (m, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.46 (br, 1H), 1.28 (m, 3H), 0.98 (m, 3H), 0.90 (d, 6H)

[0472] Example 373: (S)-Quinuclidin-3-yl (6-fluoro-5-(3-isopropylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.37~7.34 (m, 3H), 7.22 (m, 2H), 6.99 (m, 1H), 4.95 (s, 1H), 4.85 (m, 1H), 4.80 (br, 1H), 3.25 (m, 1H), 2.95 (m, 1H), 2.90~2.72 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.46 (br, 1H), 1.28 (m, 9H), 0.98 (m, 3H)

[0473] Example 374: (S)-Quinuclidin-3-yl (5-(3-(tert-butyl)phenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.53 (s, 1H), 7.41 (m, 1H), 7.35 (m, 1H), 7.22 (d, 1H), 7.01 (m, 1H), 4.95 (s, 1H), 4.85 (m, 1H), 4.80 (br, 1H), 3.80 (m, 3H), 3.25 (m, 1H), 2.90~2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.46 (br, 1H), 1.37 (s, 9H), 1.28 (m, 3H), 0.98 (m, 3H)

[0474] Example 375: (S)-Quinuclidin-3-yl (6-fluoro-5-(3-methoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 11H-NMR (400 MHz, CDCl3) δ 7.35 (m, 1H), 7.22 (m, 1H), 7.11 (m, 1H), 7.09 (s, 1H), 7.01 (m, 1H), 6.91 (d, 1H), 4.95 (s, 1H), 4.85 (m, 1H), 4.80 (br, 1H), 3.85 (s, 3H), 3.25 (m, 1H), 2.90 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.46 (br, 1H), 1.28 (m, 3H), 0.98 (m, 3H)

[0475] Example 376: (S)-Quinuclidin-3-yl (5-(3-ethoxyphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.35 (m, 1H), 7.22 (m, 1H), 7.11 (m, 1H), 7.09 (s, 1H), 7.01 (m, 1H), 6.89 (d, 1H), 4.95 (s, 1H), 4.85 (m, 1H), 4.80 (br, 1H), 4.09 (m, 2H), 3.25 (m, 1H), 2.90 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.46 (br, 1H), 1.45 (t, 3H), 1.28 (m, 3H), 0.98 (m, 3H)

[0476] Example 377: (S)-Quinuclidin-3-yl (6-fluoro-2,2-dimethyl-5-(3-propoxyphenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 11H-NMR (400 MHz, CDCl3) δ 7.33 (m, 1H), 7.22 (d, 1H), 7.11 (m, 1H), 7.09 (s, 1H), 7.01 (m, 1H), 6.90 (d, 1H), 4.95 (s, 1H), 4.85 (m, 1H), 4.80 (br, 1H), 3.96 (m, 2H), 3.25 (m, 1H), 2.90 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.80 (m, 2H), 1.70 (br, 1H), 1.59 (br, 1H), 1.46 (br, 1H), 1.28 (m, 3H), 1.15 (t, 3H), 0.98 (m, 3H)

[0477] Example 378: (S)-Quinuclidin-3-yl (6-fluoro-5-(3-isopropoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.32 (m, 1H), 7.22 (d, 1H), 7.11 (m, 1H), 7.09 (s, 1H), 7.01 (m, 1H), 6.87 (d, 1H), 4.95 (m, 2H), 4.80 (br, 1H), 4.57 (m, 1H), 3.25 (m, 1H), 2.90 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.46 (br, 1H), 1.35 (d, 6H), 1.28 (m, 3H), 0.98 (m, 3H)

[0478] Example 379: (S)-Quinuclidin-3-yl (5-(3-butoxyphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl) carbamate 11H-NMR (400 MHz, CDCl3) δ 7.34 (m, 1H), 7.22 (d, 1H), 7.10 - 7.01 (m, 3H), 6.89 (d, 1H), 4.95 (s, 1H), 4.85 (m, 1H), 4.80 (br, 1H), 4.00 (m, 2H), 3.25 (m, 1H), 2.90 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.78 (m, 2H), 1.70 (br, 1H), 1.59 (br, 1H), 1.53 (m, 2H), 1.46 (br, 1H), 1.28 (m, 3H), 0.98 (m, 6H)

[0479] Example 380: (S)-Quinuclidin-3-yl (6-fluoro-5-(3-isobutoxyphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.33 (m, 1H), 7.22 (d, 1H), 7.11 - 6.91 (m, 3H), 6.89 (d, 1H), 4.95 (s, 1H), 4.85 (m, 1H), 4.80 (br, 1H), 3.76 (d, 2H), 3.25 (m, 1H), 2.90 - 2.73 (m, 7H), 2.10 (m, 2H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.4� (br, 1H), 1.28 (m, 3H), 1.05 (d, 6H), 0.97 (m, 3H)

[0480] Example 381: (S)-Quinuclidin-3-yl (5-(2,4-dimethoxyphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.16 (d, 1H), 7.09 (d, 1H), 6.97 (m, 1H), 6.56 (m, 2H), 4.95 (s, 1H), 4.85 (m, 1H), 4.80 (br, 1H), 3.85 (s, 3H), 3.79 (s, 3H), 3.25 (m, 1H), 2.92 - 2.71 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.46 (br, 1H), 1.28 (m, 3H), 0.98 (m, 3H)

[0481] Example 382: (S)-Quinuclidin-3-yl (5-(2,5-dimethoxyphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.12 (d, 1H), 7.01 (m, 1H), 6.96 (m, 2H), 6.87 (s, 1H), 4.95 (s, 1H), 4.85 (m, 1H), 4.80 (br, 1H), 3.79 (s, 3H), 3.76 (s, 3H), 3.25 (m, 1H), 2.93 - 2.72 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.46 (br, 1H), 1.28 (m, 3H), 0.98 (m, 3H)

[0482] Example 383: (S)-Quinuclidin-3-yl (5-(2,6-dimethoxyphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.33 (m, 1H), 7.05 (d, 1H), 6.98 (m, 1H), 6.65 (d, 2H), 4.95 (s, 1H), 4.85 (m, 1H), 4.80 (br, 1H), 3.75 (s, 6H), 3.25 (m, 1H), 2.93 - 2.72 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.46 (br, 1H), 1.28 (m, 3H), 0.98 (m, 3H)

[0483] Example 384: (S)-Quinuclidin-3-yl (5-(3,5-dimethoxyphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.20 (d, 1H), 7.02 (m, 1H), 6.65 (s, 2H), 6.48 (s, 1H), 4.95 (s, 1H), 4.85 (m, 1H), 4.80 (br, 1H), 3.83 (s, 6H), 3.25 (m, 1H), 2.89 - 2.72 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.46 (br, 1H), 1.28 (m, 3H), 0.98 (m, 3H)

[0484] Example 385: (S)-Quinuclidin-3-yl (5-(3,4-dimethoxyphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.20 (d, 1H), 7.08 - 6.92 (m, 3H), 6.93 (d, 1H), 4.95 (s, 1H), 4.85 (m, 1H), 4.80 (br, 1H), 3.93 (s, 6H), 3.25 (m, 1H), 2.93 - 2.72 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.46 (br, 1H), 1.28 (m, 3H), 0.98 (m, 3H)

[0485] Example 386: (S)-Quinuclidin-3-yl (5-(2-chloro-4-methoxyphenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.21 (d, 1H), 7.06 (d, 1H), 7.03 - 7.00 (m, 2H), 6.86 (d, 1H), 4.95 (s, 1H), 4.85 (m, 1H), 4.80 (br, 1H), 3.84 (s, 3H), 3.25 (m, 1H), 2.90 - 2.72 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.46 (br, 1H), 1.28 (m, 3H), 0.98 (m, 3H)

[0486] Example 387: (S)-Quinuclidin-3-yl (5-(4-ethoxy-3-fluorophenyl)-6-fluoro-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.29 (m, 1H), 7.23 (m, 1H), 7.17 (d, 1H), 7.01 (m, 2H), 4.95 (s, 1H), 4.85 (m, 1H), 4.80 (br, 1H), 4.15 (m, 2H), 3.25 (m, 1H), 2.90 - 2.73 (m, 7H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.47 (t, 3H), 1.45 (br, 1H), 1.28 (m, 3H), 0.98 (m, 3H)

[0487] Example 388: (S)-Quinuclidin-3-yl (6-fluoro-5-(4-isopropoxyl-3,5-dimethylphenyl)-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.19 - 7.00 (m, 3H), 6.97 (m, 1H), 4.95 (m, 1H), 4.85 (m, 1H), 4.80 (br, 1H), 4.21 (m, 1H), 3.25 (m, 1H), 2.90 - 2.73 (m, 7H), 2.31 (s, 6H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.45 (br, 1H), 1.30 (d, 6H), 1.28 (m, 3H), 0.98 (m, 3H)

[0488] Examples 389 to 398 Using (S)-quinucidin-3-yl (5'-bromo-1',3'-dihydrospiro[cyclopropane-1,2'-inden]-1'-yl) carbamate prepared in Production Example 8; and the corresponding substituted phenylboronic acid respectively, the title compounds of Examples 389 to 398 were produced according to the same procedure as in Example 1.

[0489] Example 389: (S)-quinucidin-3-yl (5'-(4-fluorophenyl)-1',3'-dihydrospiro[cyclopropane-1,2'-inden]-1'-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.54 (m, 2H), 7.42 (m, 2H), 7.38 (s, 1H), 7.13 (t, 2H), 5.02 (m, 1H), 4.93 (m, 1H), 4.74 (m, 1H), 3.25 (m, 1H), 3.10 (m, 1H), 2.91 - 2.72 (m, 6H), 2.09 (m, 1H), 1.82 (m, 1H), 1.70 (br, 1H), 1.60 (m, 1H), 1.43 (br, 1H), 0.92 (m, 2H), 0.81 (m, 1H), 0.59 (m, 1H)

[0490] Example 390: (S)-quinucidin-3-yl (5'-(4-chlorophenyl)-1',3'-dihydrospiro[cyclopropane-1,2'-inden]-1'-yl) carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.55 (d, 2H), 7.47 (m, 5H), 5.02 (m, 1H), 4.91 (m, 1H), 4.77 (m, 1H), 3.25 (m, 1H), 3.10 (m, 1H), 2.91 - 2.72 (m, 6H), 2.09 (m, 1H), 1.82 (m, 1H), 1.70 (br, 1H), 1.60 (m, 1H), 1.43 (br, 1H), 0.92 (m, 2H), 0.81 (m, 1H), 0.59 (m, 1H)

[0491] (S)-Quinuclidin-3-yl (5'-(4-(trifluoromethyl)phenyl)-1',3'-dihydrospiro[cyclopropane-1,2'-indene]-1'-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.69 (s, 4H), 7.47 (m, 3H), 5.04 (m, 1H), 4.95 (m, 1H), 4.77 (m, 1H), 3.25 (m, 1H), 3.10 (m, 1H), 2.91 - 2.72 (m, 6H), 2.09 (m, 1H), 1.82 (m, 1H), 1.70 (br, 1H), 1,60 (m, 1H), 1.43 (br, 1H), 0.91 (m, 2H), 0.81 (m, 1H), 0.59 (m, 1H)

[0492] (S)-Quinuclidin-3-yl (5'-(4-(trifluoromethoxy)phenyl)-1',3'-dihydrospiro[cyclopropane-1,2'-indene]-1'-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.58 (d, 2H), 7.46 (m, 2H), 7.40 (s, 1H), 7.29 (d, 2H), 5.03 (m, 1H), 4.94 (m, 1H), 4.76 (m, 1H), 3.25 (m, 1H), 3.09 (m, 1H), 2.95 - 2.76 (m, 6H), 2.09 (m, 1H), 1.82 (m, 1H), 1.72 (br, 1H), 1,62 (m, 1H), 1.43 (br, 1H), 0.92 (m, 2H), 0.81 (m, 1H), 0.59 (m, 1H)

[0493] (S)-Quinuclidin-3-yl (5'-(3-chlorophenyl)-1',3'-dihydrospiro[cyclopropane-1,2'-indene]-1'-yl)carbamate 11H-NMR (400 MHz, CDCl3) δ 7.56 (s, 1H), 7.44 (m, 2H), 7.37 (m, 1H), 7.33 (m, 1H), 5.02 (m, 1H), 4.91 (m, 1H), 4.77 (m, 1H), 3.25 (m, 1H), 2.91 - 2.72 (m, 7H), 2.09 (m, 1H), 1.80 (m, 1H), 1.70 (br, 1H), 1.60 (m, 1H), 1.43 (br, 1H), 0.91 (m, 2H), 0.80 (m, 1H), 0.59 (m, 1H)

[0494] Example 394: (S)-Quinuclidin-3-yl (5'-(3-(trifluoromethyl)phenyl)-1',3'-dihydrospiro[cyclopropane-1,2'-indene]-1'-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.56 (s, 1H), 7.44 (m, 2H), 7.37 (m, 1H), 7.33 (m, 1H), 5.02 (m, 1H), 4.91 (m, 1H), 4.77 (m, 1H), 3.25 (m, 1H), 2.91 - 2.72 (m, 7H), 2.09 (m, 1H), 1.80 (m, 1H), 1.70 (br, 1H), 1.60 (m, 1H), 1.43 (br, 1H), 0.91 (m, 2H), 0.80 (m, 1H), 0.59 (m, 1H)

[0495] Example 395: (S)-Quinuclidin-3-yl (5'-(4-(2-methoxyethoxy)phenyl)-1',3'-dihydrospiro[cyclopropane-1,2'-indene]-1'-yl)carbamate 11H-NMR (400 MHz, CDCl3) δ 7.51 (d, 2H), 7.41 (m, 3H), 7.01 (d, 2H), 5.02 (m, 1H), 4.90 (m, 1H), 4.75 (m, 1H), 4.18 (m, 2H), 3.80 (m, 2H), 3.48 (s, 3H), 3.25 (m, 1H), 3.08 (m, 1H), 2.91 - 2.72 (m, 5H), 2.09 (m, 1H), 1.85 (br, 1H), 1.80 (m, 1H), 1.70 (br, 1H), 1.60 (m, 1H), 1.43 (br, 1H), 0.91 (m, 2H), 0.81 (m, 1H), 0.59 (m, 1H)

[0496] Example 396: (S)-Quinuclidin-3-yl (5'-(3-(2-methoxyethoxy)phenyl)-1',3'-dihydrospiro[cyclopropane-1,2'-indene]-1'-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.46 (m, 2H), 7.45 (s, 1H), 7.35 (t, 1H), 7.18 (m, 2H), 6.93 (d, 1H), 5.04 (m, 1H), 4.91 (m, 1H), 4.75 (m, 1H), 4.19 (m, 2H), 3.79 (m, 2H), 3.48 (s, 3H), 3.25 (m, 1H), 3.08 (m, 1H), 2.91 - 2.72 (m, 5H), 2.09 (m, 1H), 1.85 (br, 1H), 1.80 (m, 1H), 1.70 (br, 1H), 1.60 (m, 1H), 1.43 (br, 1H), 0.91 (m, 2H), 0.81 (m, 1H), 0.59 (m, 1H)

[0497] Example 397: (S)-Quinuclidin-3-yl (5'-(4-(methoxymethoxy)phenyl)-1',3'-dihydrospiro[cyclopropane-1,2'-indene]-1'-yl)carbamate 1H-NMR (400 MHz, CDCl3) δ 7.51 (d, 2H), 7.43 (d, 2H), 7.39 (s, 1H), 7.11 (d, 2H), 5.22 (s, 2H), 5.02 (m, 1H), 4.92 (m, 1H), 4.75 (m, 1H), 3.52 (s, 3H), 3.25 (m, 1H), 3.08 (m, 1H), 2.91 - 2.72 (m, 5H), 2.09 (m, 1H), 1.85 (br, 1H), 1.80 (m, 1H), 1.70 (br, 1H), 1.60 (m, 1H), 1.43 (br, 1H), 0.91 (m, 2H), 0.79 (m, 1H), 0.59 (m, 1H)

[0498] Example 398: (S)-Quinuclidin-3-yl (5'-(3-(methoxymethoxy)phenyl)-1',3'-dihydrospiro[cyclopropane-1,2'-inden]-1'-yl)carbamate 1 H-NMR (400 MHz, CDCl3) δ 7.46 (m, 2H), 7.45 (s, 1H), 7.35 (t, 1H), 7.18 (m, 2H), 6.93 (d, 1H), 5.22 (s, 2H), 5.02 (m, 1H), 4.92 (m, 1H), ۴.۷۵ (m, 1H), 3.51 (s, 3H), 3.25 (m, 1H), 3.08 (m, 1H), 2.91 - 2.72 (m, 5H), 2.09 (m, 1H), 1.85 (br, 1H), 1.80 (m, 1H), 1.70 (br, 1H), 1.60 (m, 1H), 1.43 (br, 1H), 0.91 (m, 2H), 0.80 (m, 1H), 0.59 (m, 1H)

[0499] Examples 399 - 403[[ID=1۲]] (S)-Quinuclidin-3-yl (5-bromo-3,3-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate prepared in Production Example 9; and the corresponding substituted phenylboronic acid were each used to produce the title compounds of Examples 399 - 403 according to the same procedure as in Example 1.

[0500] Example 399: (S)-Quinuclidin-3-yl (5-(3-chlorophenyl)-3,3-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H NMR (400 MHz, CD3OD) δ 7.62 - 7.49 (m, 2H), 7.48 - 7.29 (m, 5H), 5.23 (d, 1H), 4.80 (brs, 1H), 4.14 - 4.08 (m, 1H), 3.29 - 3.24 (m, 1H), 2.92 - 2.72 (m, 5H), 2.43 - 2.37 (m, 1H), 2.12 - 2.05 (m, 1H), 2.00 - 1.93 (m, 1H), 1.88 - 1.75 (m, 2H), 1.70 - 1.63 (m, 1H), 1.54 - 1.43 (m, 4H), 1.26 (brs, 3H)

[0501] Example 400: (S)-Quinuclidin-3-yl (5-(2-chlorophenyl)-3,3-dimethyl-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H NMR (400 MHz, CD3OD) δ 7.52 - 7.45 (m, 1H), 7.38 - 7.22 (m, 6H), 5.29 - 5.21 (m, 1H), 4.94 - 4.90 (m, 7H), 4.86 - 4.77 (m, 1H), 4.15 - 4.07 (m, 1H), 3.31 - 3.22 (m, 1H), 2.93 - 2.71 (m, 4H), 2.46 - 2.37 (m, 1H), 2.14 - 2.05 (m, 1H), 2.01 - 1.93 (m, 1H), 1.90 - 1.74 (m, 2H), 1.73 - 1.61 (m, 1H), 1.57 - 1.48 (m, 1H), 1.48 - 1.40 (m, 3H), 1.28 - 1.24 (m, 3H)

[0502] Example 401: (S)-Quinuclidin-3-yl (3,3-dimethyl-5-(3-(trifluoromethyl)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 11H NMR (400 MHz, CD3OD) δ 7.89 - 7.84 (m, 2H), 7.66 - 7.63 (m, 2H), 7.53 - 7.46 (m, 2H), 7.35 (dd, 1H), 5.26 (t, 1H), 4.83 - 4.78 (m, 1H), 3.30 - 3.26 (m, 1H), 2.92 - 2.73 (m, 5H), 2.42 (ddd, 1H), 2.14 - 2.06 (m, 1H), 1.96 (dd, 1H), 1.89 - 1.76 (m, 2H), 1.71 - 1.65 (m, 1H), 1.55 - 1.46 (m, 4H), 1.30 - 1.27 (m, 3H)

[0503] Example 402: (S)-Quinuclidin-3-yl (3,3-dimethyl-5-(3-(trifluoromethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H NMR (400 MHz, CD3OD) δ 7.62 (d, 1H), 7.56 - 7.43 (m, 4H), 7.36 - 7.24 (m, 2H), 5.24 (brs, 1H), 4.85 - 4.78 (m, 1H), 3.29 - 3.19 (m, 1H), 2.92 - 2.72 (m, 5H), 2.41 (dd, 1H), 2.10 (d, 1H), 2.03 - 1.94 (m, 1H), 1.88 - 1.76 (m, 2H), 1.71 - 1.64 (m, 1H), 1.54 - 1.44 (m, 4H), 1.28 (brs, 3H)

[0504] Example 403: (S)-Quinuclidin-3-yl (3,3-dimethyl-5-(2-(trifluoromethoxy)phenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 1 1H NMR (400 MHz, CD3OD) δ 7.50 - 7.38 (m, 4H), 7.34 - 7.28 (m, 3H), 5.26 (t, 1H), 4.83 - 4.78 (m, 1H), 3.29 - 3.26 (m, 1H), 2.92 - 2.73 (m, 5H), 2.42 (dt, 1H), 2.10 (dd, 1H), 2.00 - 1.96 (m, 1H), 1.88 - 1.77 (m, 2H), 1.70 - 1.66 (m, 1H), 1.52 (brs, 1H), 1.43 (s, 3H), 1.26 (s, 3H)

[0505] Examples 404 and 405 Using (S)-quinucidin-3-yl (6-bromo-dihydrobenzofuran-3-yl) carbamate prepared in Production Example 10; and the corresponding substituted phenylboronic acid respectively, the title compounds of Examples 404 and 405 were produced according to the same procedure as in Example 1.

[0506] Example 404: (S)-quinucidin-3-yl (6-(3-(trifluoromethyl)phenyl)-2,3-dihydrobenzofuran-3-yl) carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.78 (s, 1H), 7.30 - 7.11 (d, 1H), 7.62 - 7.60 (d, 1H), 7.56 - 7.52 (t, 1H), 7.45 - 7.41 (t, 1H), 7.17 - 7.14 (m, 1H), 7.06 (s, 1H), 5.42 (m, 2H), 4.76 - 4.72 (m, 2H), 4.44 - 4.41 (m, 1H), 3.25 - 3.19 (m, 1H), 2.82 - 2.69 (m, 5H), 2.03 - 2.00 (m, 1H), 1.77 - 1.65 (m, 2H), 1.59 - 1.57 (m, 1H), 1.45 - 1.30 (m, 1H)

[0507] Example 405: (S)-quinucidin-3-yl (6-(3-(trifluoromethoxy)phenyl)-2,3-dihydrobenzofuran-3-yl) carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.48 - 7.38 (m, 4H), 7.21 - 7.20 (d, 1H), 7.15 - 7.12 (m, 1H), 7.04 (s, 1H), 5.43 - 5.38 (m, 2H), 4.76 - 4.71 (m, 2H), 4.44 - 4.41 (m, 1H), 3.25 - 3.19 (m, 1H), 2.82 - 2.66 (m, 5H), 2.03 - 2.01 (m, 1H), 1.77 - 1.65 (m, 2H), 1.59 - 1.55 (m, 1H), 1.39 (m, 1H)

[0508] Example 406: (S)-Quinuclidin-3-yl (5-(3-fluorophenyl)-2,2-dimethyl-2,3-dihydrobenzofuran-3-yl)carbamate Using (S)-quinuclidin-3-yl (5-bromo-2,2-dimethyl-2,3-dihydrobenzofuran-3-yl)carbamate prepared in Production Example 11 and 3-fluorophenylboronic acid, the title compound was produced according to the same procedure as in Example 1. 1 1H-NMR (400 MHz, CDCl3) δ 7.52~7.44 (m, 2H), 7.38~7.27 (m, 2H), 7.23~7.21 (d, 1H), 7.02~6.98 (t, 1H), 6.85~6.83 (d, 1H), 5.22~5.19 (m, 1H), 5.09~5.07 (m, 1H), 4.76~4.74 (m, 1H), 3.26~3.20 (m, 1H), 2.82~2.64 (m, 5H), 1.77~1.68 (m, 2H), 1.66~1.53 (m, 4H), 1.46~1.39 (m, 4H), 1.27 (m, 1H)

[0509] Examples 407 to 411 Using (S)-quinuclidin-3-yl (6-bromo-2,2-dimethyl-2,3-dihydrobenzofuran-3-yl)carbamate prepared in Production Example 12 and the corresponding substituted phenylboronic acids respectively, the title compounds of Examples 407 to 411 were produced according to the same procedure as in Example 1.

[0510] Example 407: (S)-Quinuclidin-3-yl (6-(3-fluorophenyl)-2,2-dimethyl-2,3-dihydrobenzofuran-3-yl)carbamate 11H-NMR (400 MHz, CDCl3) δ 7.39~7.31 (m, 3H), 7.27~7.22 (t, 1H), 7.12~7.09 (t, 1H), 7.06~7.02 (t, 1H), 6.95 (s, 1H), 5.36~5.30 (m, 1H), 5.06~5.04 (d, 1H), 4.76~4.74 (m, 1H), 3.24~3.19 (m, 1H), 2.81~2.69 (m, 5H), 1.76~1.67 (m, 2H), 1.54~1.49 (m, 4H), 1.45~1.43 (m, 4H), 1.40~1.26 (m, 1H)

[0511] Example 408: (S)-Quinuclidin-3-yl (6-(3-chlorophenyl)-2,2-dimethyl-2,3-dihydrobenzofuran-3-yl) carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.53 (s, 1H), 7.43~7.31 (m, 4H), 7.1~7.09 (m, 1H), 6.95 (s, 1H), 5.18~5.14 (m, 1H), 5.07~5.05 (m, 1H), 4.77~4.75 (m, 1H), 3.26~3.21 (m, 1H), 2.89~2.65 (m, 5H), 1.77~1.73 (m, 2H), 1.69~1.68 (m, 4H), 1.56~1.44 (m, 4H), 1.40 (m, 1H)

[0512] Example 409: (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(3-(trifluoromethyl)phenyl)-2,3-dihydrobenzofuran-3-yl) carbamate 11H-NMR (400 MHz, CDCl3) δ 7.79 (s, 1H), 7.73 - 7.71 (d, 1H), 7.62 - 7.60 (d, 1H), 7.57 - 7.53 (t, 1H), 7.41 - 7.37 (t, 1H), 7.15 - 7.12 (t, 1H), 6.98 (s, 1H), 5.23 - 5.19 (t, 1H), 5.08 - 5.06 (d, 1H), 4.77 - 4.75 (m, 1H), 3.26 - 3.21 (m, 1H), 2.89 - 2.65 (m, 5H), 1.78 - 1.69 (m, 2H), 1.57 - 1.53 (m, 3H), 1.46 - 1.40 (m, 4H), 1.40 - 1.27 (m, 1H)

[0513] Example 410: (S)-Quinuclidin-3-yl (2,2-dimethyl-6-(3-(trifluoromethoxy)phenyl)-2,3-dihydrobenzofuran-3-yl)carbamate 1 1H-NMR (400 MHz, CDCl3) δ 7.47 - 7.43 (m, 2H), 7.39 - 7.35 (m, 2H), 7.22 - 7.20 (d, 1H), 7.13 - 7.09 (t, 1H), 6.96 (s, 1H), 5.19 - 5.14 (t, 1H), 5.08 - 5.06 (d, 1H), 4.76 - 4.75 (m, 1H), 3.27 - 3.21 (m, 1H), 2.84 - 2.66 (m, 5H), 1.77 - 1.68 (m, 2H), 1.56 - 1.53 (m, 4H), 1.46 - 1.40 (m, 4H), 1.39 - 1.27 (m, 1H)

[0514] Example 411: (S)-Quinuclidin-3-yl (6-(3-(2-methoxyethoxy)phenyl)-2,2-dimethyl-2,3-dihydrobenzofuran-3-yl)carbamate 11H-NMR (400 MHz, CDCl3) δ 7.35~7.27 (m, 2H), 7.23~7.22 (m, 2H), 7.19~7.17 (m, 1H), 7.03 (m, 1H), 6.97 (s, 1H), 5.21~5.18 (m, 3H), 5.05~5.00 (m, 1H), 4.74~4.73 (m, 1H), 3.49 (s, 3H), 3.23~3.18 (m, 1H), 2.80~2.66 (m, 5H), 2.04 (m, 1H), 1.76~1.67 (m, 2H), 1.56~1.38 (m, 8H)

[0515] Test Example 1: Evaluation of Inhibitory Activity Against GCS The inhibitory activity of the compound of the present invention against GCS was evaluated as follows according to the method described in a known document (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). Ibiglustat, known as a GCS inhibitor, was used as a reference substance.

[0516] (1) Materials A549 cells (ATCC, CCL-185) NBD C6-ceramide (Thermo Fisher, N1154) UDP-glucose (Sigma, U4625) Potassium chloride (Sigma, P9333) UltraPure TM 0.5 M EDTA (Invitrogen, 15575-038) BCA Protein Assay Kit (Thermo Fisher, 23227) Ibiglustat (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)

[0517] (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 in an incubator at 37°C and 5% CO2. The cells attached to the culture dish were washed with phosphate-buffered saline (PBS), then scraped off with a cell scraper, centrifuged (4000 rpm, 3 minutes, 4°C), and the cells were collected in a 50 ml tube. The cell pellet was suspended in lysis buffer (containing 50 mM HEPES, pH 7.3, 1x Protease / Phosphatase Inhibitor Cocktail), lysed by sonication, and then the lysate was centrifuged (13000 rpm, 10 minutes, 4°C). The resulting supernatant was used for quantitative analysis of proteins. The amount of protein was measured using a BCA protein assay kit with bovine serum albumin as a standard.

[0518] <2>GCS enzyme reaction The enzyme reaction was initiated by sequentially adding the following reactants to a 96-deep well plate. Subsequently, the enzyme reaction was carried out at 37 °C for 90 minutes.

Table 1

[0519] <3>Lipid extraction The enzyme reaction was stopped by adding 100 μl of chloroform / methanol (2:1, v / v). After vortexing for 15 seconds, each mixture was centrifuged (4000 rpm, 10 minutes, 18 °C). The lower layer (50 μl) was transferred to a new 96-deep well plate and dried using a vacuum concentrator.

[0520] <4>HPLC analysis The lipid was dissolved in 100 μl of isopropyl alcohol / n-hexane / H2O (55:44:1, v / v / v) and transferred to a glass vial for HPLC (Agilent, 8004-HP-H / i3u). The sample (100 μl) was automatically loaded onto a normal-phase column (Intersil SIL 150A-5, 4.6 x 250 mm, GL Sciences, Japan) and eluted with isopropyl alcohol / n-hexane / H2O (55:44:1, v / v / v) at a flow rate of 2.0 ml / min. Its fluorescence was measured using a fluorescence detector (Agilent, 1260 FLD Spectra) with excitation and emission wavelengths of 470 nm and 530 nm, respectively.

[0521] <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 calculate the IC 50 value. The results are shown in Tables 1 to 4 below.

Table 2

Table 3

Table 4

Table 5

[0522] From the results of Tables 1 to 4, it can be seen that the compounds of the present invention exhibit excellent inhibitory activity against GCS.

[0523] Test Example 2: Evaluation of Inhibitory Activity against GM1 Production Since GM1, the final product of sphingolipid metabolism, is expressed on the cell membrane, it is easy to detect. Furthermore, the amount of GM1 represents the conversion from ceramide to glucosylceramide. Therefore, the inhibitory activity of the compounds of the present invention against GM1 production was evaluated as follows according to the method described in a known document (Dijkhuis et al., Gangliosides do not affect ABC transporter function in human neuroblastoma cells. The Journal of Lipid Research 47 (2006). 1187-1195). Ibiglustat, known as a GCS inhibitor, was used as a reference substance.

[0524] (1) Materials Jurkat cells, clone E6-1 (ATCC, TIB-152) Cholera toxin subunit B (CTB), FITC (Sigma, C1655) Ibrutinib (Shanghai Systeam Biochem Co., ltd, Genz-682452) DMSO (Sigma, D2650) Fixing 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. The washing solution was prepared by adding 10 ml of FBS to 490 ml of FACS sheath fluid. The CTB-FITC solution was prepared by diluting the CTB-FITC stock solution (10 mg / ml) with the washing solution to a final concentration of 2 μg / ml.

[0525] (2) Protocol Cell suspension (1X10 5cells / ml) were prepared in a medium (RPMI 1640 medium supplemented with 10% FBS and 1X Antibiotic - Antimycotic). After adding the cell suspension (200 μl) to each well of a 96 - well plate (20,000 cells / well), the compound was added at a final concentration of 0.05 - 3000 nM (3 - fold, 11 points) per well and treated. Each mixture was incubated at 37 °C for 72 hours in a CO2 incubator. After centrifuging at 1500 rpm for 3 minutes to remove the medium, the cells were resuspended in 200 μl of washing solution per well. After centrifuging 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 without exposure to light. After centrifuging 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 2 more times. After centrifuging the washed plate at 1500 rpm for 3 minutes to remove the washing solution, the cells were completely resuspended in 200 μl of fixing buffer. IC 50 was determined from the values obtained by quantifying the FITC fluorescence using a Guava TM easyCyte 5HT (Merck Milipore, 0500 - 4005).

[0526] Data analysis was performed according to the following formula. %MFI (Median Fluorescence Intensity) = (Fluorescence value of the drug - treated group / Fluorescence value of the DMSO - treated group) × 100 % Cells = (Cell concentration in the well / Cell concentration of the DMSO - treated group) × 100 %MFI and % Cells data were analyzed using the software GraphPad Prism (Ver 5.01) to calculate the IC 50 value. The results are shown in Tables 5 - 8 below.

Table 6

Table 7

Table 8

Table 9

[0527] From the results of Tables 5 to 8, it can be seen that the compounds of the present invention exhibit excellent inhibitory activity against GM1 production.

Claims

1. A process for producing a compound of Chemical Formula 1a or a pharmaceutically acceptable salt thereof, comprising reacting a compound of Chemical Formula 5 with an A-W-boronic acid substituted with X １ , X ２ , X ３ , or X ４ to obtain a compound of Chemical Formula 1a; and optionally, converting the compound of Chemical Formula 1a into its pharmaceutically acceptable salt. 【Chemical 1】 【Chemical 2】 (wherein, Y and Z are each independently, -CR １ R ２ -; -NR ３ -; -O-; or -S-; and R １ and R ２ each independently represents hydrogen; halogen; C １ -C ６ alkyl; C having a nitrogen atom, an oxygen atom, or a sulfur atom １ -C ６ alkyl; C ３ -C １０ cycloalkyl; a heterocyclic group having 3 to 12 members; or C １ -C ６ alkoxy, or R １ and R ２ together with the carbon atom to which they are attached form C ３ -C １０ cycloalkyl, R ３ is hydrogen; C １ to C ６ alkyl; C having a nitrogen atom, an oxygen atom, or a sulfur atom １ to C ６ alkyl; C ３ to C １０ cycloalkyl; a heterocyclic group having 3 to 12 members; or C １ to C ６ alkoxy, X is hydrogen; halogen; C １ ~C ６ alkyl; C substituted with 1 to 3 halogens １ ~C ６ alkyl; C having a nitrogen atom, an oxygen atom, or a sulfur atom １ ~C ６ alkyl; C １ ~C ６ alkoxy; or C substituted with 1 to 3 halogens １ ~C ６ is alkoxy, W is a bond, -CH ２ -, -O-, -NH-, -CH ２ CH ２ -, -CH=CH-, or -C≡C-, and Ring A is aryl of 6 to 12 members; heteroaryl of 5 to 12 members; C ３ -C １０ cycloalkyl; or a heterocyclic group of 3 to 12 members, and X １ , X ２ , X ３ , and X ４ is, independently of one another, hydrogen; cyano; halogen; C １ - C ６ alkyl; C １ - C ６ alkoxy-C １ - C ６ alkyl; C １ - C ６ alkyl substituted with 1 to 3 halogens; C ３ - C １０ cycloalkyl; a 3- to 12-membered heterocyclic group; C １ - C ６ alkoxy; C １ - C ６ alkoxy substituted with 1 to 3 halogens; C １ - C ６ alkoxy-C １ - C ６ alkoxy; morpholinyl-C １ - C ６ alkoxy; mono- or di-C １ - C ６ alkylamino-C １ - C ６ alkoxy; C ３ - C １０ cycloalkyl-C １ - C ６ alkoxy; C １ - C ６ alkylthio; amino; mono- or di-C １ - C ６ alkylamino; C １ - C ６ alkylcarbonyl; hydroxy; or nitro.)

2. The compound of Formula 5 and X １ , X ２ , X ３ , or X ４ The production method according to claim 1, wherein the reaction with the A-W-boronic acid substituted with is carried out using a palladium catalyst.

3. The compound of Chemical Formula 5 and X １ , X ２ , X ３ , or X ４ The production method according to claim 1, wherein the reaction with the A-W-boronic acid substituted with is carried out in the presence of an inorganic base.

4. The production method according to any one of Claims 1 to 3, wherein the compound of Chemical Formula 5 is obtained by coupling the compound of Chemical Formula 3 with quinuclidinol. 【Chemical Formula 3】 (wherein, X, Y and Z are the same as those defined in Claim 1.)

5. The production method according to Claim 4, wherein the coupling is carried out by a condensation reaction including removal of ethanol.

6. The production method according to Claim 4 or 5, wherein the compound of Chemical Formula 3 is obtained by reacting the compound of Chemical Formula 2 or a salt thereof with ethyl chloroformate. 【Chemical Formula 4】 (wherein, X, Y and Z are the same as those defined in Claim 1.)

7. The production method according to Claim 6, wherein the reaction between the compound of Chemical Formula 2 or a salt thereof and ethyl chloroformate is carried out in the presence of a base.

8. The production method according to any one of Claims 1 to 3, wherein the compound of Chemical Formula 5 is obtained by reacting the compound of Chemical Formula 7 with the compound of Chemical Formula 2. [Chemical Formula 5] 【Chemical Formula 6】 (wherein, X, Y and Z are the same as those defined in Claim 1.)

9. The production method according to Claim 8, wherein the reaction between the compound of Chemical Formula 7 and the compound of Chemical Formula 2 is carried out in the presence of a base.

10. The production method according to Claim 8 or 9, wherein the compound of Chemical Formula 7 is obtained by reacting quinuclidinol with bis(4-nitrophenyl) carbonate.

11. The production method according to Claim 8 or 9, wherein the compound of Chemical Formula 7 is obtained by reacting quinuclidinol with 4-nitrophenyl chloroformate.

12. The compound of Chemical Formula 5: [Chemical Formula 7] (wherein, Y and Z are each independently, -CR １ R ２ -; -NR ３ -; -O-; or -S-; and R １ and R ２ each independently represents hydrogen; halogen; C １ -C ６ alkyl; C having a nitrogen atom, an oxygen atom, or a sulfur atom １ -C ６ alkyl; C ３ -C １０ cycloalkyl; a heterocyclic group having 3 to 12 members; or C １ -C ６ alkoxy, or R １ and R ２ together with the carbon atom to which they are attached form C ３ -C １０ cycloalkyl, R ３ is hydrogen; C １ to C ６ alkyl; C having a nitrogen atom, an oxygen atom, or a sulfur atom １ to C ６ alkyl; C ３ to C １０ cycloalkyl; a heterocyclic group having 3 to 12 members; or C １ to C ６ alkoxy, and X is hydrogen; halogen; C １ ~C ６ alkyl; C substituted with 1 to 3 halogens １ ~C ６ alkyl; C having a nitrogen atom, an oxygen atom, or a sulfur atom １ ~C ６ alkyl; C １ ~C ６ alkoxy; or C substituted with 1 to 3 halogens １ ~C ６ alkoxy.

13. Y and Z are each independently -O- or -CR １ R ２ - and R １ and R ２ each independently is hydrogen or C １ to C ６ alkyl, or R １ and R ２ together with the carbon atom to which they are attached form C ３ to C １０ cycloalkyl, the compound according to claim 12.

14. Y is -O-, and Z is -CR １ R ２ -, the compound according to claim 12.

15. X is hydrogen, halogen, or C １ to C ６ The compound according to claim 12, which is alkoxy.

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