Indole derivatives, process for preparation of the same and use thereof

TECHNICAL FIELD

[0001] The present invention relates to indole derivatives.

[0002] More specifically, the present invention relates to indole derivatives represented by formula (I):

[0003] (wherein all symbols have the same meanings as described below), a process for the preparation of the same and use thereof.

BACKGROUND ART

[0004] Prostaglandin D (hereinafter referred to as “PGD”) are known as a metabolite in the arachidonic acid cascade, and are known to have effects of bronchoconstriction, vasodilatation or vasoconstriction and platelet aggregation inhibition. PGD is considered to be produced from mast cells, and the increase of PGD concentration has been recognized among systemic mastocytosis patients (New Eng. J. Med., 303, 1400-1404 (1980)). Also, PGD is considered to relate to neuro activities, especially, sleep and hormone secretion. Furthermore, there are reports suggesting participations in platelet aggregation, glycogen metabolism, ocular tension adjustment and the like.

[0005] PGD shows its effects by binding to a DP receptor which is a receptor thereof. A DP receptor antagonist binds to and is antagonistic to its receptor so that it can inhibit the function of PGD. Accordingly, it is considered to be useful for the prevention and/or treatment of diseases, for example, allergic diseases such as allergic rhinitis, allergic conjunctivitis, atopic dermatitis, bronchial asthma, food allergy, etc.; systemic mastocytosis; disorders due to systemic mastocyte activation; anaphylactic shock; bronchoconstriction; urticaria; eczema; allergic bronchopulmonary aspergillosis; inflammatory paranasal sinus; nasal polyp; hypersensitive angitis; eosinophilia; contact dermatitis; diseases accompanied with itching, such as atopic dermatitis, urticaria, allergic conjunctivitis, allergic rhinitis, contact dermatitis, etc.; secondary diseases caused by behaviors (scratching behaviors, beating, etc.), such as cataract, retinal detachment, inflammation, infection, sleep disorder, etc.; inflammation; chronic obstructive pulmonary disease; ischemic reperfusion disorder; cerebrovascular disorder; pleuritis complicated by rheumatoid arthritis; ulcerative colitis; and the like. Moreover, it is considered to relate to sleeping and platelet aggregation and to be useful for these diseases.

[0006] Some DP receptor antagonists are known until now, and BW-A868C represented by formula (A) is considered to be the most selective:

[0007] Also, recently, DP receptor antagonists which are thromboxane derivatives have been published in WO 98/25915, WO 98/25919, WO 97/00853, WO 98/15502 and the like.

[0008] On the other hand, as a compound similar to the compound of the present invention, an indole compound represented by formula (B) is known as a synthetic intermediate (J. Heterocyclic Chem., 19, 1195 (1982)).

DISCLOSURE OF THE INVENTION

[0009] The present inventors intensively studied to find a compound which specifically binds to DP receptor and show an antagonistic activity and found that the object could be attained by indole derivatives represented by formula (I), and thus the present invention has been completed.

[0010] That is, the present invention relates to an indole derivative represented by formula (I):

[0011] wherein R1 represents hydroxy, C1-6 alkoxy, or NR8R9, in which R8 and R9 each independently represents a hydrogen atom, C1-6 alkyl, or SO2R13, in which R13 represents C1-6 alkyl, a C3-15 saturated or unsaturated carbocyclic ring or a 4- to 15-membered heterocyclic ring containing 1 to 5 nitrogen atom(s), sulfur atom(s) and/or oxygen atom(s);

[0012] R2 represents a hydrogen atom, C1-6 alkyl, C1-6 alkoxy, C2-6 alkoxyalkyl, a halogen atom, amino, trihalomethyl, cyano, hydroxy, benzyl, or 4-methoxybenzyl;

[0013] R3 represents a hydrogen atom, C1-6 alkyl, C1-6 alkoxy, a halogen atom, trihalomethyl, cyano, or hydroxy;

[0014] R4 and R5 each independently represents a hydrogen atom, C1-6 alkyl, C1-6 alkoxy, C2-6 alkoxyalkyl, a halogen atom, nitro, amino, trihalomethyl, cyano, or hydroxy;

[0015] D represents a single bond, C1-6 alkylene, C2-6 alkenylene, or C1-6 oxyalkylene;

[0016] in -G-R6,

[0017] 1) G represents a single bond, C1-6 alkylene which may be substituted with 1 to 2 oxygen atom(s) and/or sulfur atom(s), C2-6 alkenylene which may be substituted with 1 to 2 oxygen atom(s) and/or sulfur atom(s), in which the alkylene and the alkenylene may be substituted with hydroxy or C1-4 alkoxy, —C(O)NH—, —NHC(O)—, —SO2NH—, —NHSO2—, or diazo;

[0018] R6 represents a C3-15 saturated or unsaturated carbocyclic ring, or a 4- to 15-membered heterocyclic ring containing 1 to 5 nitrogen atom(s), sulfur atom(s) and/or oxygen atom(s), in which the ring may be substituted with 1 to 5 substituent(s) selected from C1-6 alkyl, C1-10 alkoxy, C2-6 alkoxyalkyl, a halogen atom, hydroxy, trihalomethyl, nitro, amino, phenyl, phenoxy, oxo, C2-6 acyl, C1-6 alkanesulfonyl and cyano,

[0019] 2) G and R6 are taken together to represent

[0020] (i) C1-15 alkyl which may be substituted with 1 to 5 oxygen atom(s) and/or sulfur atom(s);

[0021] (ii) C2-15 alkenyl which may be substituted with 1 to 5 oxygen atom(s) and/or sulfur atom(s); or

[0022] (iii) C2-15 alkynyl which may be substituted with 1 to 5 oxygen atom(s) and/or sulfur atom(s),

[0023] in which the alkyl, the alkenyl and the alkynyl may be substituted with 1 to 12 substituent(s) selected from C1-6 alkoxy, a halogen atom, hydroxy, cyano, oxo and NR11R12, in which R11 and R12 each independently represents a hydrogen atom, C1-6 alkyl, C2-6 alkenyl, phenyl, benzoyl, naphthyl, phenyl substituted with C1-6 alkyl, or C1-6 alkyl substituted with phenyl or cyano;

[0024] n represents 1 to 3;

[0025] m represents 1 to 3;

[0026] i represents 1 to 4; and

[0027]

represents a single bond or a double bond, or a non-toxic salt thereof;

[0028] (2) a process for the preparation thereof;

[0029] (3) a pharmaceutical agent comprising it as an active ingredient; and

[0030] (4) 2-methylindole-4-acetic acid which is a novel synthetic intermediate.

[0031] In formula (I), the C1-6 alkyl represented by R2, R3, R4, R5, R6, R8, R9, R11, R12 or R13 includes, methyl, ethyl, propyl, butyl, pentyl, hexyl, and isomers thereof.

[0032] In formula (I), the C1-6 alkoxy represented by R1, R2, R3, R4 or R5 includes methoxy, ethoxy, propyloxy, butyloxy, pentyloxy, hexyloxy, and isomers thereof.

[0033] In formula (I), the C1-10 alkoxy represented by R6 includes methoxy, ethoxy, propyloxy, butyloxy, pentyloxy, hexyloxy, heptyloxy, octyloxy, nonyloxy, decyloxy, and isomers thereof.

[0034] In formula (I), the C1-15 alkyl represented by G and R6 taken together includes methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, and isomers thereof.

[0035] In formula (I), the C1-15 alkyl which may be substituted with 1 to 5 oxygen atom(s) and/or sulfur atom(s) represented by G and R6 taken together represents the above alkyl in which any 1 to 5 carbon atom(s) are substituted with an oxygen atom(s) and/or a sulfur atom(s).

[0036] In formula (I), the C2-15 alkenyl represented by G and R6 which are taken together includes vinyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, dodecenyl, tridecenyl, tetradecenyl, pehtadecenyl, and isomers thereof.

[0037] In formula (I), the C2-15 alkenyl which may be substituted with 1 to 5 oxygen atom(s) and/or sulfur atom(s) represented by G and R6 which are taken together represents the above alkenyl in which any 1 to 5 carbon atom(s) are substituted with an oxygen atom(s) and/or a sulfur atom(s).

[0038] In formula (I), the C2-15 alkynyl represented by G and R6 which are taken together includes ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl, decynyl, undecynyl, dodecynyl, tridecynyl, tetradecynyl, pentadecynyl, and isomers thereof.

[0039] In formula (I), the C2-15 alkynyl which may be substituted with 1 to 5 oxygen atom(s) and/or sulfur atom(s) represented by G and R6 which are taken together represents the above alkynyl in which any 1 to 5 carbon atom(s) are substituted with an oxygen atom(s) and/or a sulfur atom(s).

[0040] In formula (I), the C2-6 alkoxyalkyl represented by R2, R4, R5 or R6 includes methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, ethoxybutyl, propyloxymethyl, propyloxyethyl, propyloxypropyl, butyloxymethyl, butyloxyethyl, pentyloxymethyl, and isomers thereof.

[0041] In formula (I), the C1-6 alkylene represented by D or G includes methylene, ethylene, trimethylene, tetramethylene, pentamethylene, hexamethylene, and isomers thereof.

[0042] In formula (I), the C2-6 alkenylene represented by D includes vinylene, propenylene, butenylene, pentenylene, hexenylene, and isomers thereof.

[0043] In formula (I), the C1-6 oxyalkylene represented by D includes oxymethylene, oxyethylene, oxybutylene, oxypehtylene, oxyhexylene, and isomers thereof.

[0044] In formula (I), the C1-6 alkylene which may by substituted with 1 to 2 oxygen atom(s) and/or sulfur atom(s) represented by G includes the above C1-6 alkylene in which any carbon atom(s) is/are substituted with an oxygen atom(s) and/or a sulfur atom(s).

[0045] In formula (I), the C2-6 alkenylene which may by substituted with 1 to 2 oxygen atom(s) and/or sulfur atom(s) represented by G includes the above C2-6 alkenylene in which any saturated carbon atom(s) is/are substituted with an oxygen atom(s) and/or a sulfur atom(s).

[0046] In formula (I), the C2-6 alkenyl represented by R11 or R12 includes vinyl, propenyl, butenyl, pentenyl, hexenyl, and isomers thereof.

[0047] In formula (I), the halogen atom represented by R2, R3, R4, R5 or R6 includes fluorine, chlorine, bromine, and iodine.

[0048] In formula (I), the trihalomethyl represented by R2, R3, R4, R5 or R6 includes trifluoromethyl, trichloromethyl, tribromomethyl, and triiodomethyl.

[0049] In formula (I), the C1-10 alkoxy represented by R10 includes methoxy, ethoxy, propyloxy, butyloxy, pentyloxy, hexyloxy, heptyloxy, octyloxy, nonyloxy, decyloxy, and isomers thereof.

[0050] In formula (I), the C2-6 acyl represented by R6 includes acetyl, propionyl, butyly, valeryl, hexanoyl, and isomers thereof.

[0051] In formula (I), the C1-6 alkanesulfonyl represented by R6 includes methanesulfonyl, ethanesulfonyl, propanesulfonyl, butanesulfonyl, pentanesulfonyl, hexanesulfonyl, and isomers thereof.

[0052] In formula (I), the C3-15 carbocyclic ring represented by R6 or R13 includes monocyclic, bicyclic or tricyclic unsaturated or saturated carbocyclic ring having carbon numbers of 3 to 15.

[0053] Examples of the monocyclic, bicyclic or tricyclic unsaturated or saturated carbocyclic ring having carbon numbers of 3 to 15 include cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane, cyclopentene, cyclohexene, cyclopentadiene, cyclohexadiene, benzene, pentalene, indene, naphthalene, azulene, perhydropentalene, perhydroindene, dihydronaphthalene, tetrahydronaphthalene, perhydronaphthalene, perhydroazulene, heptalene, biphenylene, fluorene, phenanthrene, anthracene, dihydroanthracene, tetrahydroanthracene, perhydroanthracene, fluorene, dihydrofluorene, tetrahydrofluorene, perhydrofluorene, norbornane, norpinane, norbornane, norbornene, norpinane, norpinene rings and the like.

[0054] In formula (I), the 4- to 15-membered heterocyclic ring containing 1 to 5 nitrogen atom(s), sulfur atom(s) and/or oxygen atom(s) represented by R6 or R13 is unsaturated or saturated, and examples includes the following formulas:

[0055] In formula (I), R1 is preferably hydroxy, C1-6 alkyl or NR8R9, and more preferably hydroxy or C1-8 alkyl.

[0056] In formula (I), R2 is preferably a hydrogen atom, C1-6 alkyl or C1-6 alkoxyalkyl, and more preferably a hydrogen atom, C1-2 alkyl or C1-2 alkoxyalkyl.

[0057] In formula (I), R3 is preferably a hydrogen atom or C1-6 alkyl.

[0058] In formula (I), R4 is preferably a hydrogen atom or C1-6 alkyl, and more preferably a hydrogen atom or C1-2 alkyl.

[0059] In formula (I), R5 is preferably a hydrogen atom or C1-6 alkyl, and more preferably a hydrogen atom or C1-2 alkyl.

[0060] In formula (I), D is preferably a single bond or C1-6 alkylene, and more preferably a single bond or C1-2 alkylene.

[0061] In formula (I), G is preferably C1-6 alkylene which may be substituted with 1 or 2 oxygen atom(s), and more preferably C1-2 alkylene which may be substituted with one oxygen atom.

[0062] In formula (I), R6 is preferably a C5-10 carbocyclic ring or a monocyclic or bicyclic 5- to 10-membered heterocyclic ring containing 1 to 3 nitrogen, oxygen and/or sulfur atom(s), which each may be substituted, and more preferably a bicyclic 9- or 10-membered heterocyclic ring containing 1 to 3 nitrogen, oxygen and/or sulfur atoms(s) which may be substituted.

[0063] Also, G and R6 are preferably taken together to represent C1-10 alkyl which may be substituted with 1 to 4 oxygen and/or sulfur atom(s), C2-10 alkenyl which may be substituted with 1 to 4 oxygen and/or sulfur atom(s), or C2-10 alkynyl which may be substituted with 1 to 4 oxygen and/or sulfur atom(s).

[0064] Unless otherwise indicated, all isomers are included in the present invention. For example, the alkyl, alkenyl and alkynyl groups and alkylene group include straight-chain groups and branched-chain groups. In addition, isomers in double bond, ring, fused ring (E-, Z-, cis-, trans-isomer), isomers generated from asymmetric carbon atom(s) (R-, S-, α-, β-isomer, enantiomer, diastereomer), optically active isomers having optical rotation (D-, L-, d-, I-isomer), polar compounds separated by chromatography (high polar compound, low polar compound), equilibrium compounds, mixtures thereof at arbitrary ratios and racemic mixtures are included in the present invention.

[0065] Among the compounds of the present invention represented by formula (I), preferred compounds are compounds shown in Examples, compounds represented by formula (I-A1):

[0066] (wherein when R6 represents a ring, R61 represents a substituent of the ring; p is 0 or an integer of 1 to 3; and other symbols have the same meanings as described above), formula (I-A2):

[0067] (wherein all symbols have the same meanings as described above), formula (I-A3):

[0068] (wherein all symbols have the same meanings as described above), formula (I-A4):

[0069] (wherein all symbols have the same meanings as described above), formula (I-A5):

[0070] (wherein all symbols have the same meanings as described above), formula (I-A6):

[0071] (wherein all symbols have the same meanings as described above), formula (I-A7):

[0072] (wherein all symbols have the same meanings as described above), formula (I-A8):

[0073] (wherein all symbols have the same meanings as described above), formula (I-A9):

[0074] (wherein all symbols have the same meanings as described above), formula (I-A10):

[0075] (wherein all symbols have the same meanings as described above), formula (I-B1)1

[0076] (wherein all symbols have the same meanings as described above), formula (I-B2):

[0077] (wherein all symbols have the same meanings as described above), formula (I-B3):

[0078] (wherein all symbols have the same meanings as described above), formula (I-B4):

[0079] (wherein all symbols have the same meanings as described above), formula (I-B5):

[0080] (wherein all symbols have the same meanings as described above), formula (I-B6):

[0081] (wherein all symbols have the same meanings as described above), formula (I-B7):

[0082] (wherein all symbols have the same meanings as described above), formula (I-B8):

[0083] (wherein all symbols have the same meanings as described above), formula (I-C1):

[0084] (wherein all symbols have the same meanings as described above), formula (I-C2):

[0085] (wherein all symbols have the same meanings as described above), formula (I-C3):

[0086] (wherein all symbols have the same meanings as described above), formula (I-C4):

[0087] (wherein all symbols have the same meanings as described above), formula (I-C5):

[0088] (wherein all symbols have the same meanings as described above), formula (I-C6):

[0089] (wherein all symbols have the same meanings as described above), formula (I-C7):

[0090] (wherein all symbols have the same meanings as described above), formula

[0091] (wherein all symbols have the same meanings as described above), formula (I-C9):

[0092] (wherein all symbols have the same meanings as described above), formula (I-C10):

[0093] (wherein all symbols have the same meanings as described above), formula (I-C11):

[0094] (wherein all symbols have the same meanings as described above), formula (I-C12)

[0095] (wherein all symbols have the same meanings as described above), formula (I-C13)

[0096] (wherein all symbols have the same meanings as described above), formula (I-C14)

[0097] (wherein all symbols have the same meanings as described above), formula (I-C15):

[0098] (wherein all symbols have the same meanings as described above), formula (I-D1):

[0099] (wherein all symbols have the same meanings as described above), formula (I-D2):

[0100] (wherein all symbols have the same meanings as described above), formula (I-D3):

[0101] (wherein all symbols have the same meanings as described above), formula (I-D4):

[0102] (wherein all symbols have the same meanings as described above), formula (I-D5):

[0103] (wherein all symbols have the same meanings as described above), formula (I-D6):

[0104] (wherein all symbols have the same meanings as described above), formula (I-D7):

[0105] (wherein all symbols have the same meanings as described above), formula (I-D8):

[0106] (wherein all symbols have the same meanings as described above), formula (I-D9):

[0107] (wherein all symbols have the same meanings as described above), formula (I-E1):

[0108] (wherein all symbols have the same meanings as described above), formula (I-E2):

[0109] (wherein all symbols have the same meanings as described above), formula (I-E3):

[0110] (wherein all symbols have the same meanings as described above), formula (I-E4):

[0111] (wherein all symbols have the same meanings as described above), formula (I-E5):

[0112] (wherein all symbols have the same meanings as described above), formula (I-E6):

[0113] (wherein all symbols have the same meanings as described above), formula (I-E7):

[0114] (wherein all symbols have the same meanings as described above), formula (I-E8):

[0115] (wherein all symbols have the same meanings as described above), formula (I-E9):

[0116] (wherein all symbols have the same meanings as described above), formula (I-E10):

[0117] (wherein all symbols have the same meanings as described above), formula (I-E12):

[0118] (wherein all symbols have the same meanings as described above), formula (I-E12):

[0119] (wherein all symbols have the same meanings as described above), formula (I-E13):

[0120] (wherein all symbols have the same meanings as described above), formula (I-E14):

[0121] (wherein all symbols have the same meanings as described above), formula (I-E15):

[0122] (wherein all symbols have the same meanings as described above), formula (I-E16):

[0123] (wherein all symbols have the same meanings as described above), formula (I-E17):

[0124] (wherein all symbols have the same meanings as described above), formula (I-E18):

[0125] (wherein all symbols have the same meanings as described above), formula (I-E19):

[0126] (wherein all symbols have the same meanings as described above), formula (I-E20):

[0127] (wherein all symbols have the same meanings as described above), formula (I-E21)

[0128] (wherein all symbols have the same meanings as described above), formula (I-E22)

[0129] (wherein all symbols have the same meanings as described above), formula (I-E23):

[0130] (wherein all symbols have the same meanings as described above), formula (I-F1):

[0131] (wherein all symbols have the same meanings as described above), formula (I-F2):

[0132] (wherein all symbols have the same meanings as described above), formula (I-F3):

[0133] (wherein all symbols have the same meanings as described above), formula (I-F4):

[0134] (wherein all symbols have the same meanings as described above), formula (I-F5):

[0135] (wherein all symbols have the same meanings as described above), formula (I-F6):

[0136] (wherein all symbols have the same meanings as described above), formula (I-F7):

[0137] (wherein all symbols have the same meanings as described above), formula (I-F8):

[0138] (wherein all symbols have the same meanings as described above), formula (I-F9):

[0139] (wherein all symbols have the same meanings as described above), formula (I-F10):

[0140] (wherein all symbols have the same meanings as described above), formula (I-F11):

[0141] (wherein all symbols have the same meanings as described above), formula (I-F12):

[0142] (wherein all symbols have the same meanings as described above), formula (I-F13):

[0143] (wherein all symbols have the same meanings as described above), formula (I-F14):

[0144] (wherein all symbols have the same meanings as described above), compounds shown in Tables 1 to 5, and non-toxic salts of the compounds.

1TABLE 1(1)

—G—R6

100

101

102

103

104

105

106

107

108

109

110

111

112

113

114

115

116

117

118

119

120

121

[0145]

2

TABLE 2

(2)

122

—G—R6

123

124

125

126

127

128

129

130

131

132

133

134

135

136

137

[0146]

3

TABLE 3

138

—G—R6

139

140

141

142

143

144

145

146

147

148

149

150

151

152

153

154

155

156

157

[0147]

4

TABLE 4

(4)

158

—G—R6

159

160

161

162

163

164

165

166

167

168

169

170

171

172

173

[0148]

5

TABLE 5

(5)

174

—G—R6

175

176

177

178

179

180

181

182

183

184

185

186

187

188

189

190

191

192

193

[0149] Salt:

[0150] The compound of the present invention represented by formula (I) can be converted into a corresponding salt by known methods. The salt is preferably a non-toxic and water-soluble salt. Appropriate salts include salts of alkali metals (potassium, sodium, etc.), salts of alkaline earth metals, ammonium salts (tetramethylammonium, tetrabutylammonium salts, etc.), and pharmaceutically acceptable organic amines (triethylamine, methylamine, dimethylamine, cyclopentylamine, benzylamine, phenethylamine, piperidine, monoethanolamine, diethanolamine, tris(hydroxymethyl)methylamine, lysine, arginine, N-methyl-D-glucamine, etc.).

[0151] The compound of the present invention represented by formula (I) and a salt thereof can also be converted into a hydrate by known methods.

[0152] Processes for the Preparation of the Compound of the Present Invention:

[0153] The compound of the present invention represented by formula (I) can be prepared by the following processes and the processes shown in Examples.

[0154] (a) Among the compounds represented by formula (I), a compound wherein R1 is hydroxy, i.e., a compound represented by formula (Ia):

194

[0155] (wherein all symbols have the same meanings as described above) can be prepared by subjecting to a deprotection reaction a compound represented by formula (IV):

195

[0156] (wherein R20 is an allyl or benzyl group; and other symbols have the same meanings as described above).

[0157] The deprotection reaction of ally ester or benzyl ester is known, for example, it is carried out in an organic solvent (e.g., methanol, ethanol, tetrahydrofuran, dioxane, ethyl acetate, etc.) at −10 to 90° C. by

[0158] 1) using tetrakis(triphenylphosphine)palladium and morpholine, or

[0159] 2) using palladium carbon, palladium, platinum, sponge nickel (trade name: Raney Nickel), etc. under hydrogen atmosphere.

[0160] (b) Among the compounds represented by formula (I), a compound wherein R1 is C1-6 alkoxy (wherein all symbols have the same meanings as described above), i.e., a compound represented by formula (Ib):

196

[0161] (wherein R10 represents C1-6 alkyl; and other all symbols have the same meanings as described above) can be prepared by subjecting to an esterification reaction a compound represented by formula (Ia) with a compound represented by formula:

R10—OH (II)

[0162] (wherein all symbols have the same meanings as described above), followed by optionally a deprotection reaction.

[0163] The esterification reaction is known, for example, it is carried out in an inert organic solvent (tetrahydrofuran, methylene chloride, benzene, acetone, acetonitrile, a mixture thereof, etc.) in the presence or absence of a tertiary amine (dimethylaminopyridine, pyridine, triethylamine, etc.) using a condensing agent (1,3-dicyclohexylcarbodiimide (DCC), 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC), etc.) or acid halide (oxalyl chloride, thionyl chloride, phosphorus oxychloride, etc.) at 0 to 50° C.

[0164] (c) Among the compounds represented by formula (I), a compound wherein R1 is —NR8R9 (wherein all symbols have the same meanings as described above), i.e., a compound represented by formula (Ic):

197

[0165] (wherein all symbols have the same meanings as described above) can be prepared by subjecting to an amidation reaction a compound represented by formula (Ia) with a compound represented by formula:

HNR10R11 (II)

[0166] (wherein all symbols have the same meanings as described above), followed by optionally a deprotection reaction.

[0167] The amidation reaction is known, for example, it is carried out in an inert organic solvent (tetrahydrofuran, methylene chloride, benzene, acetone, acetonitrile, a mixture thereof, etc.) in the presence or absence of a tertiary amine (dimethylaminopyridine, pyridine, triethylamine, etc.) using a condensing agent (1,3-dicyclohexylcarbodiimide (DCC), 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC), etc.) or acid halide (oxalyl chloride, thionyl chloride, phosphorus oxychloride, etc.) at of 0 to 50° C.

[0168] The compound represented by formula (IV) can prepared by subjecting to a compound represented by formula (V):

198

[0169] (wherein R21, R31 and R41 have the same meanings as R2, R3 and R4, respectively, and when they represent an amino group or a hydroxy group, they are protected with a protecting group; and other symbols have the same meanings as described above) with a compound represented by formula (VI):

199

[0170] (wherein R51 has the same meaning as R5, and when it represents an amino group or a hydroxy group, it is protected with a protecting group; and G1 and R61 have the same meanings as G and R6, respectively, and when they contains an amino group or a hydroxy group, it is protected with a protecting group), followed by optionally a deprotection reaction. The amidation reaction can be carried out by the above method.

[0171] The compounds represented by formula (II), (III), (V) and (VI) are known per se or can be prepared by known methods.

[0172] Among the compounds represented by formula (Ia), a compound wherein D is alkylene can be prepared by reducing a compound represented by formula (Ia), or can be prepared by increasing the carbon of the alkylene part.

[0173] In each reaction in the present specification, reaction products can be purified by conventional purification techniques, e.g., by distillation under atmospheric or reduced pressure, high performance liquid chromatography, thin layer chromatography or column chromatography using silica gel or magnesium silicate, washing, recrystallization or the like. Purification can be carried out after each reaction or after some reactions.

[0174] Pharmacological Activities:

[0175] The compound of the present invention represented by formula (I) potently binds to a DP receptor and show an antagonistic activity. For example, in a laboratory test, such effects were confirmed by the following receptor binding test using prostanoid receptor-expressing cells.

[0176] (i) Receptor Binding Test Using Prostanoid DP Receptor-Expressing Cells

[0177] CHO cells expressing a mouse DP receptor was prepared according to the method of Hirata et al. (Proc. Natl. Acad. Sci., 91, 11192-11196 (1994)) and used as a membrane standard.

[0178] A reaction solution (200 μL) containing the prepared membrane standard (30-166 μg) and 3H-PGD2 was incubated at room temperature for 20 minutes. The reaction was stopped with an ice-cold buffer (1 mL) and the binding 3H-PGD2 was trapped in on a glass filter by immediate aspiration-filtration under a reduced pressure, and its binding radioactivity was measured using a liquid scintillation counter.

[0179] A Kd value and a Bmax value were obtained from Scatchard plots (Ann. N.Y. Acad. Sci., 51, 660 (1949)). Non-specific binding was obtained as the binding radioactivity in the presence of unlabeled PGD2 at an excess amount (10 μmol/L). 3H-PGD2 binding inhibition by the compound of the present invention was measured by adding 3H-PGD2 (2.5 mmol/L) and the compound of the present invention as various concentrations. Also, the following buffers were used for the reactions.

[0180] Incubation buffer:

[0181] HEPES-NaOH (25 mmol/L, pH 7.4)

[0182] EDTA (1 mmol/L)

[0183] MgCl2 (5 mmol/L)

[0184] MnCl2 (10 mmol/L)

[0185] Buffer for washing:

[0186] Tris-HCl (10 mmol/L, pH 7.5)

[0187] NaCl (0.1 mol/L)

[0188] Bovine serum albumin (0.01%)

[0189] The dissociation constant (Ki) (μmol/L) of each compound was obtained by the following equation.

[0190] Ki=IC50/(1+([L]*/Kd))

[0191] [L*]: Concentration of radioligand

[0192] The results are shown in Table 6.

6TABLE 6Example No.DP Ki (μM)1(3)0.00181(4)0.0043

[0193] As shown in the above results, it is apparent that the compound of the present invention potently binds to a DP receptor.

[0194] (ii) DP Antagonistic Activity Assay Using Prostanoid DP Receptor-Expressing Cells

[0195] CHO cells expressing a mouse DP receptor were prepared according to the method of Nishigaki et al. (FEBS lett., 364, 339-341 (1995)), inoculated onto a 24-well microplate at 105 cells/well, followed by culturing for 2 days, and used for the assay. Each well was washed with 500 μL of MEM (minimum essential medium), and 450 μL of assay medium (MEM containing 1 mmol/L IBMX and 0.1 or 1% BSA), followed by incubation at 37° C. for 10 minutes. Then, an assay medium (50 μL) containing PGD2 alone or PGD2 with a test compound was added thereto to start the reaction, and after the reaction at 37° C. for 10 minutes, 500 μL of ice-cold trichloroacetatic acid (TCA) (10% w/v) was added thereto to stop the reaction. The reaction solution was frozen once (−80° C.) and thawed, and cells were peeled using a scraper, followed by centrifugation at 13,000 rpm for 3 minutes. The cAMP concentration was measured with a cAMP assay kit using the resulting supernatant. That is, [125I]-cAMP assay kit buffer was added to 125 μL of the supernatant to give a total amount of 500 μL, and the resulting mixture was mixed with 1 mL of a chloroform solution of 0.5 mol/L tri-n-octylamine. Trichloro acetic acid (TCA) was extracted to the chloroform layer and removed, the cAMP amount in a sample was determined using the aqueous layer as the sample according to the method described in the [125I]cAMP assay kit.

[0196] Also, with regard to the antagonistic activity (IC50) of the test compound, the IC50 value was calculated as an inhibition rate based on the reaction at 100 nM which was a concentration showing submaximal cAMP production by PGD2 alone.

7TABLE 7DP antagonisticExample No.activity IC50 (μM)1(3)0.12

[0197] As shown in the above results, it is apparent that the compound of the present invention has an antagonistic activity against a DP receptor.

[0198] Toxicity:

[0199] The toxicity of the compound represented by formula (I) of the present invention is very low so that it is confirmed that the compound is sufficiently safe for using as a pharmaceutical.

INDUSTRIAL APPLICABILITY

[0200] Application to Pharmaceuticals:

[0201] Since the compound of the present invention represented by formula (I) bind to and is antagonistic to a DP receptor, it is considered that the compound is useful for the prevention and/or treatment of diseases, for example, allergic diseases such as allergic rhinitis, allergic conjunctivitis, atopic dermatitis, bronchial asthma, food allergy, etc.; systemic mastocytosis; disorders due to systemic mastocyte activation; anaphylactic shock; bronchoconstriction; urticaria; eczema; allergic bronchopulmonary aspergillosis; inflammatory paranasal sinus; nasal polyp; hypersensitive angitis; eosinophilia; contact dermatitis; diseases accompanied with itching, such as atopic dermatitis, urticaria, allergic conjunctivitis, allergic rhinitis, contact dermatitis, etc.; secondary diseases caused by behaviors (scratching behaviors, beating, etc.), such as cataract, retinal detachment, inflammation, infection, sleep disorder, etc.; inflammation; chronic obstructive pulmonary disease; ischemic reperfusion disorder; cerebrovascular disorder; pleuritis complicated by rheumatoid arthritis; ulcerative colitis; and the like. Moreover, the compound is considered to relate to sleeping and platelet aggregation and to be useful for these diseases.

[0202] Among the compounds of the present invention represented by formula (I), one having a weak binding activity to a compound other than a DP receptor would be used as a pharmaceutical having less side effects because it does not show other activity.

[0203] When the compound represented by formula (I) of the present invention, a non-toxic salt or a cyclodextrin inclusion compound thereof is normally administered systemically or topically and orally or parenterally.

[0204] The dosages are determined depending on age, body weight, symptom, therapeutic effect, administration route, duration of the treatment and the like. Generally, 1 μg to 100 mg per adult is orally administered once to several times per day, or 0.1 μg to 10 mg per adult is parenterally administered (preferably by intravenous administration) once to several times per day, or continuously administered from vein for 1 to 24 hours per day.

[0205] Since the dose changes depending on various conditions as described above, there are cases in which doses lower than or greater than the above ranges may be used.

[0206] The compounds of the present invention may be administered in the form of solid compositions, liquid compositions or other compositions for oral administration, and injections, liniments, suppositories and the like for parenteral administration.

[0207] Solid compositions for oral administration include compressed tablets, pills, capsules, dispersible powders, granules and the like.

[0208] Capsules include hard capsules and soft capsules.

[0209] In such solid compositions, one or more active compound(s) is/are mixed with at least one inert diluent such as lactose, mannitol, glucose, hydroxypropyl cellulose, microcrystalline cellulose, starch, polyvinyl pyrrolidone or magnesium metasilicate aluminate.

[0210] The compositions may also contain additional substances other than inert diluents, e.g., lubricating agents such as magnesium stearate, disintegrating agents such as cellulose calcium glycolate, and assisting agents for dissolving such as glutamic acid, asparatic acid according to usual methods. The tablets or pills may, if desired, be coated with film of gastric- or enteric-coating agents such as sugar, gelatin, hydroxypropyl cellulose or hydroxypropyl cellulose phthalate, or be coated with two or more films. Furthermore, capsules of absorbable materials such as gelatin are included

[0211] Liquid compositions for oral administration include pharmaceutically acceptable emulsions, solutions, syrups and elixirs. In such compositions, one or more active compound(s) is/are dissolved, suspended or emulsified in an inert diluent commonly used (e.g., purified water, ethanol). Furthermore, such liquid compositions may also contain wetting agents or suspending agents, emulsifying agents, sweetening agents, flavoring agents, perfuming agents, and preserving agents.

[0212] Other compositions for oral administration include sprays containing one or more active compound(s) which are prepared by known methods. Spray compositions may contain stabilizing agents such as sodium hydrogen sulfate, stabilizing agents to give isotonicity, isotonic solutions such as sodium chloride, sodium citrate or citric acid, other than inert diluents. The process for preparing the sprays are described in U.S. Pat. Nos. 2,868,691 and 3,095,355.

[0213] Injections for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions and emulsions. Aqueous solutions or suspensions include, for example, distilled water for injection and a physiological salt solution. Non-aqueous solutions or suspensions include propylene glycol, polyethylene glycol, plant oil such as olive oil, alcohol such as ethanol, POLYSORBATE80 (registered trade mark), and the like.

[0214] Such compositions may contain additional diluents such as preserving agents, wetting agents, emulsifying agents, dispersing agents, stabilizing agents, assisting agents such as assistant agents for dissolving (e.g., glutamic acid, aspartic acid). They may be sterilized by filtration through a bacteria-retaining filter, or incorporation or irradiation of a sterilizing agent. They may also be manufactured in the form of sterile solid compositions which can be dissolved in sterile water or other sterile diluent for injection immediately before use.

[0215] Other compositions for parenteral administration include liquids for external use, endemic liniments, ointments, suppositories for intrarectal administration and pessaries for intravaginal administration containing one or more active compound(s) which can be prepared by known methods.

BEST MODE FOR CARRYING OUT THE INVENTION

[0216] The following Reference Examples and examples illustrate the present invention, but do not limit the present invention.

[0217] In the following chemical formula, Tf represents a trifluoromethanesulfoxy group, Boc represents a t-butoxycarbonyl group, TMS represents a trimethylsilyl group, and Bn represents a benzyl group.

[0218] The solvents in the parentheses show the developing or eluting solvents and the ratios of the solvents used are by volume in chromatographic separations or TLC.

[0219] The solvents in the parentheses in NMR show the solvents for measurement.

REFERENCE EXAMPLE 1

[0220] 2-Methyl-4-trifluoromethanesulfoxyindole

200

[0221] A solution of 2-methyl-4-hydroxyindole (10 g) in methylene chloride (100 ml) was stirred at 0° C. To the solution was added lutidine (10.28 ml) and trifluoromethanesulfonic anhydride (13.72 ml), and the solution was maintained at the same temperature for 1 hours. To the mixture was added water and then extracted with ethyl acetate. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with water and a saturated aqueous solution of sodium chloride, successively, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give the title compound having the following physical data. The compound was used to next reaction without further purification.

[0222] TLC: Rf 0.57 (hexane:ethyl acetate=7:3).

REFERENCE EXAMPLE 2

[0223] 1-t-Butoxycarbonyl-2-methyl-4-trifluoromethanesulfoxyindole

201

[0224] To a solution of 2-methyl-4-trifluoromethanesulfoxyindole (1 g; prepared in Reference Example 1) and di-t-butyl dicarbonate (1 ml) in acetonitrile (12 ml) was added dimethylaminopyridine (catalytic amounts), and the mixture was stirred at room temperature overnight. To the reaction solution was added water and ethyl acetate, and then the mixture was separated. The organic layer was washed with water and a saturated aqueous solution of sodium chloride, successively, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give the title compound (1.38 g) having the following physical data.

[0225] TLC: Rf 0.50 (hexane:ethyl acetate=1:1).

REFERENCE EXAMPLE 3

[0226] 1-t-Butoxycarbonyl-2-methyl-4-(2-trimethylsilylethynyl)indole

202

[0227] To a solution of 1-t-butoxycarbonyl-2-methyl-4-trifluoromethanesulfoxyindole (17.9 g; prepared in Reference Example 2), dichlorobis(triphenylphosphine)palladium (1.6 g), copper iodide (0.88 g) and tetrabutylammonium iodide (3.4 g) in N,N-dimethylformamide (180 ml) was added trimethylsilylacetylene (11 ml), and the mixture was stirred at 65° C. for 2 hours. To the mixture was added 0.5N hydrochloric acid—ethyl acetate, and then insoluble material was removed by filtration through Celite (trademark). The organic layer was washed with water (twice) and a saturated aqueous solution of sodium chloride, successively, dried and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=10:1) to give the title compound (15.0 g) having the following physical data.

[0228] NMR (CDCl3): δ 8.09-8.05 (d, J=8.5 Hz, 1H), 7.32-7.29 (m, 1H), 7.17-7.08 (m, 1H), 6.49 (s, 1H), 2.61 (s, 3H), 0.29 (s, 9H).

REFERENCE EXAMPLE 4

[0229] 1-t-Butoxycarbonyl-2-methylindole-4-acetic Acid

203

[0230] A solution of cyclohexane (16.1 ml) in tetrahydrofuran (160 ml) was cooled at −10° C., and then to the mixture was added dropwise borane-tetrahydrofuran complex (1M, 80 ml), and the mixture was stirred at 0° C. for 1 hour. To the solution was added dropwise a solution of 1-t-butoxycarbonyl-2-methyl-4-(2-trimethylsilylethynyl)indole (13.1 g; prepared in Reference Example 3) in tetrahydrofuran (60 ml), the mixture was stirred for 1 hour at room temperature. To a reaction solution was added dropwise 3N aqueous solution of sodium hydroxide (40 ml) and 30% hydrogen peroxide (in water, 45 ml), successively, and the mixture was stirred for 12 hours. The reaction mixture was extracted with water—diethyl ether. The aqueous layer was adjusted to acidic condition with hydrochloric acid and then extracted with ethyl acetate. The extraction was washed with water and a saturated aqueous solution of sodium chloride, successively, dried and concentrated under reduced pressure to give the title compound (10.4 g; crude).

REFERENCE EXAMPLE 5

[0231] 2-Methylindole-4-acetic Acid

204

[0232] To a mixture of 1-t-butoxycarbonyl-2-methylindole-4-acetic acid (96.3 g) in methanol (200 ml)—water (100 ml) was added dropwise 5N aqueous solution of sodium hydroxide (200 ml) at room temperature, and the mixture was stirred at 50° C. for 3 hours and then stirred at room temperature for 12 hours. The reaction mixture was extracted with hexane—ether. The aqueous layer was adjusted to acidic condition with hydrochloric acid and then extracted with ethyl acetate. The extraction was washed with water and a saturated aqueous solution of sodium chloride, successively, dried and concentrated under reduced pressure to give the title compound (53.9 g; crude).

[0233] In addition, this intermediate compound is novel compound that does not have a publication in literature.

REFERENCE EXAMPLE 6

[0234] 2-Methylindole-4-acetic Acid Allyl Ester

205

[0235] To a solution of 2-methylindole-4-acetic acid (53 g) in N,N-dimethylformamide (500 ml) was added dropwise allyl bromide (31 ml), and added anhydrous potassium carbonate (59 g). The mixture was stirred at 50° C. for 1 hour. After cooling to room temperature, the reaction mixture was poured into a mixture of 2N hydrochloric acid—ethyl acetate and then extracted with ethyl acetate. The extraction was washed with water and a saturated aqueous solution of sodium chloride, successively, dried and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (hexane—ethyl acetate) to give the title compound (43.5 g) having the following physical data.

[0236] TLC: Rf 0.50 (hexane:ethyl acetate=1:2);

[0237] NMR (CDCl3): δ 7.92 (brs, 1H), 7.19 (d, J=7.0 Hz, 1H), 7.06 (t, J=1H), 6.96 (dd, J=7.0, 1.2 Hz, 1H), 6.27 (m, 1H), 5.90 (ddt, J=17.2, 10.4, 5.4 Hz, 1H), 5.25 (d, J=17.2 Hz, 1H), 5.18 (d, J=10.4 Hz, 1H), 4.59 (m, 2H), 3.88 (s, 2H), 2.43 (s, 3H).

REFERENCE EXAMPLE 7

[0238] 4-(2-Propyloxyethoxy)benzoic Acid

206

[0239] To a solution of 4-hydroxybenzoic acid (3.04 g) and anhydrous potassium carbonate (5.52 g) in N,N-dimethylformamide (20 ml) was added 2-propyloxyethyl chloride (2.94 g), and the mixture was stirred at room temperature overnight, and then stirred at 80° C. for 8 hours. To a reaction solution was added water, and then the mixture was extracted with ethyl acetate. The organic layer was washed with water and a saturated aqueous solution of sodium chloride, successively, dried and concentrated under reduced pressure to give the title compound (5.21 g; crude).

[0240] TLC: Rf 0.47 (hexane:ethyl acetate=2:1).

REFERENCE EXAMPLE 8

[0241] 1-(4-(2-Propyloxyethoxy)benzoyl)-2-methylindole-4-acetic Acid Allyl Ester

207

[0242] To a solution of 4-(2-propyloxyethoxy)benzoic acid (448 mg; prepared in Reference Example 7) in toluene (5 ml) was added N,N-dimethylformamide (catalytic amounts) and oxalyl chloride (350 μl), and the mixture was stirred for 30 minutes at room temperature, then concentrated. A solution of the residue in methylene chloride (2 ml) was added to a solution of 2-methylindole-4-acetic acid allyl ester (230 mg; prepared in Reference Example 6), sodium hydroxide (200 mg) and tetrabutylammonium chloride (15 mg) in methylene chloride (8 ml), and the mixture was stirred for 30 minutes at room temperature. To a reaction solution was added 1N hydrochloric acid—ethyl acetate. The organic layer was washed with water and a saturated aqueous solution of sodium chloride, successively, dried and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane—ethyl acetate) to give the title compound (276 mg) having the following physical data.

[0243] TLC: Rf 0.39 (hexane:ethyl acetate=2:1).

EXAMPLE 1

[0244] 1-(4-(2-Propyloxyethoxy)benzoyl)-2-methylindole-4-acetic Acid

208

[0245] To a solution of 1-(4-(2-propyloxyethoxy)benzoyl)-2-methylindole-4-acetic acid allyl ester (276 mg; prepared in Reference Example 8) and morpholine (275 μl) in tetrahydrofuran (3 ml) was added tetrakis(triphenylphosphine)palladium (35 mg) and the mixture was stirred for 2 hours at room temperature. To the reaction solution was added 1 N hydrochloric acid—ethyl acetate. The organic layer was washed with water and a saturated aqueous solution of sodium chloride, successively, dried and concentrated under reduced pressure. The residue was dissolved in hexane—ethyl acetate (½) and then the insoluble material was filtered off. To the filtrate was added cyclohexylamine (70 mg) and the mixture was stirred for 30 minutes at room temperature. The reaction solution was filtered. To the obtained crystal was added 1N hydrochloric acid—ethyl acetate. The organic layer was washed with water and a saturated aqueous solution of sodium chloride, successively, dried and concentrated to give the compound of the present invention (204 mg) having the following physical data.

[0246] TLC: Rf 0.20 (ethyl acetate);

[0247] NMR (CDCl3): δ 7.71-7.69 (m, 2H), 7.04-6.92 (m, 5H), 6.48 (s, 1H), 4.23-4.19 (m, 2H), 3.86 (s, 2H), 3.86-3.81 (m, 2H), 3.51 (t, J=7.0 Hz, 2H), 2.44 (s, 3H), 1.65 (tq, J=7.0, 7.5 Hz, 2H), 0.94 (t, J=7.5 Hz, 3H).

EXAMPLES 1 (1) TO 1 (75)

[0248] Each compound having the following physical data was obtained by the same procedures as a series of reactions of Reference Examples 1, 2, 3, 4, 5, 6, 7, 8 and Example 1. In Example 1(8), 1(51), 1(67), 1(68) and 1(69), hydroxy or amino group was protected by protective group, and the protective group was removed before the reaction corresponding Example 1.

Example 1(1)

[0249] 1-(4-Butoxybenzoyl)-2-methylindole-4-acetic Acid

209

[0250] TLC: Rf 0.46 (chloroform:methanol=9:1);

[0251] NMR (CDCl3): δ 7.70 (d, J=9.0 Hz, 2H), 7.08-6.90 (m, 5H), 6.49 (s, 1H), 4.05 (t, J=6.6 Hz, 2H), 3.87 (s, 2H), 2.45 (s, 3H), 1.88-1.74 (m, 2H), 1.80-1.40 (br, 1H), 1.60-1.45 (m, 2H), 1.00 (t, J=7.5 Hz, 3H).

Example 1(2)

[0252] 1-(4-Propyloxybenzoyl)-2-methylindole-4-acetic Acid

210

[0253] TLC: Rf 0.52 (chloroform:methanol=10:1);

[0254] NMR (CDCl3): δ 7.74-7.69 (m, 2H), 7.12-6.90 (m, 5H), 6.49 (s, 1H), 4.01 (t, J=6.6 Hz, 2H), 3.87 (s, 2H), 2.45 (s, 3H), 1.86 (dt, J=7.5, 6.6 Hz, 2H), 1.07 (t, J=7.5 Hz, 3H).

Example 1(3)

[0255] 1-(4-(2-Phenoxy)benzoyl)-2-methylindole-4-acetic Acid

211

[0256] TLC: Rf 0.60 (chloroform:methanol=10:1);

[0257] NMR (CDCl3): δ 7.72-7.66 (m, 2H), 7.38-7.23 (m, 5H), 7.07-6.92 (m, 5H), 6.49 (s, 1H), 4.26 (t, J=6.9 Hz, 2H), 3.86 (s, 2H), 3.14 (t, J=6.9 Hz, 2H), 2.44 (s, 3H).

Example 1(4)

[0258] 1-(4-Pentyloxybenzoyl)-2-methylindole-4-acetic Acid

212

[0259] TLC: Rf 0.64 (chloroform:methanol=10:1);

[0260] NMR (CDCl3): δ 7.73-7.66 (m, 2H), 7.07-6.92 (m, 5H), 6.49 (s, 1H), 4.04 (t, J=6.6 Hz, 2H), 3.87 (s, 2H), 2.44 (s, 3H), 1.86-1.23 (m, 6H), 0.95 (t, J=6.9 Hz, 3H).

Example 1(5)

[0261] 1-(4-1-Pentyloxybenzoyl)-2-methylindole-4-acetic Acid

213

[0262] TLC: Rf 0.34 (chloroform:methanol=10:1);

[0263] NMR (CDCl3): δ 7.73-7.67 (m, 2H), 7.06-6.91 (m, 5H), 6.48 (s, 1H), 4.07 (t, J=6.6 Hz, 2H), 3.86 (s, 2H), 2.45 (s, 3H), 1.84 (m, 1H), 1.72 (m, 2H), 0.98 (d, J=6.4 Hz, 6H).

Example 1(6)

[0264] 1-(4-(2-Ethoxyethoxy)benzoyl)-2-methylindole-4-acetic Acid

214

[0265] TLC: Rf 0.50 (chloroform:methanol=10:1);

[0266] NMR (CDCl3): δ 7.70 (d, J=8.7 Hz, 2H), 7.08-6.92 (m, 5H), 6.49 (s, 1H), 4.21 (t, J=4.8 Hz, 2H), 3.87-3.81 (m, 4H), 3.62 (q, J=7.5 Hz, 2H), 2.45 (s, 3H), 1.26 (t, J=7.5 Hz, 3H).

Example 1(7)

[0267] 1-(4-Benzyloxybenzoyl)-2-methylindole-4-acetic Acid

215

[0268] TLC: Rf 0.55 (chloroform:methanol=10:1);

[0269] NMR (CDCl3): δ 7.65-7.33 (d, J=8.8 Hz, 2H), 7.45-7.36 (m, 5H), 7.05-6.90 (m, 5H), 6.48 (s, 1H), 5.14 (s, 2H), 3.85 (s, 2H), 2.43 (d, J=1.0 Hz, 3H).

Example 1(8)

[0270] 1-(4-(2-(4-Hydroxyphenyl)ethoxy))benzoyl)-2-methylindole-4-acetic Acid

216

[0271] TLC: Rf 0.30 (chloroform:methanol=10:1);

[0272] NMR (CDCl3): δ 7.68 (d, J=8.6 Hz, 2H), 7.14 (d, J=8.2 Hz, 2H), 7.08-6.89 (m, 5H), 6.78 (d, J=8.0 Hz, 2H), 6.48 (s, 1H), 4.20 (t, J=7.0 Hz, 2H), 3.85 (s, 2H), 3.05 (t, J=7.0 Hz, 2H), 2.43 (s, 3H).

Example 1(9)

[0273] 1-(4-Butoxybenzoyl)indole-4-acetic Acid

217

[0274] TLC: Rf 0.25 (hexane:ethyl acetate=1:1);

[0275] NMR (CDCl3): δ 8.26 (d, J=8.2 Hz, 1H), 7.72-7.68 (m, 2H), 7.38-7.16 (m, 3H), 7.00-6.96 (m, 2H), 6.65 (d, J=3.6 Hz, 1H), 4.05 (t, J=6.4 Hz, 2H), 3.87 (s, 2H), 1.82 (m, 2H), 1.52 (m, 2H), 1.00 (t, J=7.2 Hz, 3H).

Example 1(10)

[0276] 1-(4-(3-Phenylpropyl)benzoyl)-2-methylindole-4-acetic Acid

218

[0277] TLC: Rf 0.61 (chloroform:methanol=10:1);

[0278] NMR (CDCl3): δ 7.64 (d, J=8.0 Hz, 2H), 7.38-7.16 (m, 7H), 7.08-6.93 (m, 3H), 6.49 (s, 1H), 3.85 (s, 2H), 2.82-2.60 (m, 4H), 2.42 (s, 3H), 2.05 (m, 2H).

Example 1(11)

[0279] 1-(4-(2-(4-Methoxyphenyl)ethoxy)benzoyl)-2-methylindole-4-acetic Acid

219

[0280] TLC: Rf 0.50 (chloroform:methanol=10:1);

[0281] NMR (CDCl3): δ 7.72-7.65 (m, 2H), 7.23-7.17 (m, 2H), 7.06-6.84 (m, 7H),6.47 (s, 1H), 4.21 (t, J=7.0 Hz, 2H), 3.85 (s, 2H), 3.80 (s, 3H), 3.08 (t, J=7.0 Hz, 2H), 2.43 (s, 3H).

Example 1(12)

[0282] 1-(4-(2-(2-Pyridyl)ethoxy)benzoyl)-2-methylindole-4-acetic Acid

220

[0283] TLC: Rf 0.40 (chloroform:methanol=9:1);

[0284] NMR (CDCl3) δ 8.59 (d, J=5.2 Hz, 1H), 7.68-6.88 (m, 10H), 6.52 (s, 1H), 4.39 (t, J=6.6 Hz, 2H), 3.86 (s, 2H), 3.31 (t, J=6.6 Hz, 2H), 2.43 (s, 3H).

Example 1(13)

[0285] 1-(4-(2-Cyclopropylethoxy)benzoyl)-2-methylindole-4-acetic Acid

221

[0286] TLC: Rf 0.37 (ethyl acetate);

[0287] NMR (CDCl3): δ 7.73-7.69 (m, 2H), 7.08-6.94 (m, 5H), 6.49 (s, 1H), 4.12 (t, J=6.5 Hz, 2H), 3.87 (s, 2H), 2.45 (s, 3H), 1.72 (q, J=6.5 Hz, 2H), 0.96-0.80 (m, 1H), 0.56-0.47 (m, 2H), 0.18-0.13 (m, 2H).

Example 1(14)

[0288] 1-(4-(2-i-Propoxyethoxy)benzoyl)-2-methylindole-4-acetic Acid

222

[0289] TLC: Rf 0.35 (ethyl acetate);

[0290] NMR (CDCl3): δ 7.72-7.67 (m, 2H), 7.04-6.90 (m, 5H), 6.48 (s, 1H), 4.22-4.17 (m, 2H), 3.86 (s, 2H), 3.84-3.80 (m, 2H), 3.78-3.62 (m, 1H), 2.44 (s, 3H), 1.21 (d, J=6.0 Hz, 6H).

Example 1(15)

[0291] 1-(4-(4-Methoxybenzyloxy)benzoyl)-2-methylindole-4-acetic Acid

223

[0292] TLC: Rf 0.33 (ethyl acetate);

[0293] NMR (CDCl3): δ 7.74-7.69 (m, 2H), 7.40-7.35 (m, 2H), 7.08-6.92 (m, 7H), 6.49 (s, 1H), 5.07 (s, 2H), 3.87 (s, 2H), 3.83 (s, 3H), 2.45 (s, 3H).

Example 1(16)

[0294] 1-(4-(2-Ethylthioethoxy)benzoyl)-2-methylindole-4-acetic Acid

224

[0295] TLC: Rf 0.50 (chloroform:methanol=10:1);

[0296] NMR (CDCl3): δ 7.71 (d, J=9.0 Hz, 2H), 7.05-6.93 (m, 5H), 6.48 (s, 1H), 4.22 (t, J=6.8 Hz, 2H), 3.86 (s, 2H), 2.95 (t, J=6.8 Hz, 2H), 2.67 (q, J=7.4 Hz, 2H), 2.44 (s, 3H), 1.31 (t, J=7.4 Hz, 3H).

Example 1(17)

[0297] 1-(4-(3,3-Dimethylbutoxy)benzoyl)-2-methylindole-4-acetic Acid

225

[0298] TLC: Rf 0.45 (chloroform:methanol=10:1);

[0299] NMR (CDCl3): δ 7.68 (d, J=8.8 Hz, 2H), 7.08-6.86 (m, 5H), 6.47 (s, 1H), 4.09 (t, J=7.2 Hz, 2H), 3.83 (s, 2H), 2.43 (s, 3H), 1.76 (t, J=7.2 Hz, 2H), 1.00 (s, 9H).

Example 1(18)

[0300] 1-(4-Benzyloxymethylbenzoyl)-2-methylindole-4-acetic Acid

226

[0301] TLC: Rf 0.50 (chloroform:methanol=10:1);

[0302] NMR (CDCl3): δ 7.72 (d, J=8.4 Hz, 2H), 7.48 (d, J=8.4 Hz, 2H), 7.39-7.31 (m, 4H), 7.06-6.96 (m, 4H), 6.50 (s, 1H), 4.66 (s, 2H), 4.63 (s, 2H), 3.86 (s, 2H), 2.42 (s, 3H).

Example 1(19)

[0303] 1-(4-(3-Ethoxypropoxy)benzoyl)-2-methylindole-4-acetic Acid

227

[0304] TLC: Rf 0.22 (ethyl acetate:hexane=3:1);

[0305] NMR (CDCl3): δ 7.70 (d, J=9.0 Hz, 2H), 7.10-6.86 (m, 5H), 6.49 (s, 1H), 4.16 (t, J=6.4 Hz, 2H), 3.86 (s, 2H), 3.62 (t, J=6.4 Hz, 2H), 3.51 (q, J=6.8 Hz, 2H), 2.45 (s, 3H), 2.09 (m, 2H), 1.21 (t, J=6.8 Hz, 3H).

Example 1(20)

[0306] 1-(4-(4-Methylpentyloxy)benzoyl)-2-methylindole-4-acetic Acid

228

[0307] TLC: Rf 0.43 (ethyl acetate:hexane=3:1);

[0308] NMR (CDCl3): δ 7.70 (d, J=8.6 Hz, 2H), 7.07-6.88 (m, 5H), 6.48 (s, 1H), 4.03 (t, J=6.8 Hz, 2H), 3.86 (s, 2H), 2.45 (s, 3H), 1.92-1.73 (m, 2H), 1.73-1.52 (m, 1H), 1.43-1.11 (m, 2H), 0.94 (d, J=6.8 Hz, 6H).

Example 1(21)

[0309] 1-(4-(2-(3-Fluorophenyl)ethoxy)benzoyl)-2-methylindole-4-acetic Acid

229

[0310] TLC: Rf 0.45 (chloroform:methanol=10:1);

[0311] NMR (CDCl3): δ 7.69 (d, J=8.8 Hz, 2H), 7.35-7.20 (m, 2H), 7.09-6.85 (m, 7H), 6.47 (s, 1H), 4.25 (t, J=6.6 Hz, 2H), 3.84 (s, 2H), 3.12 (t, J=6.6 Hz, 2H), 2.42 (s, 3H).

Example 1(22)

[0312] 1-(4-(2-(3-Methoxyphenyl)ethoxy)benzoyl)-2-methylindole-4-acetic Acid

230

[0313] TLC: Rf 0.35 (ethyl acetate);

[0314] NMR (CDCl3): δ 7.72-7.68 (m, 2H), 7.44-7.36 (m, 1H), 7.28-7.22 (m, 2H), 7.06-6.88 (m, 6H), 6.48 (s, 1H), 4.24 (t, J=7.0 Hz, 2H), 3.86 (s, 5H), 3.15 (t, J=7.0 Hz, 2H), 2.44 (s, 3H).

Example 1(23)

[0315] 1-(4-(2-(2-Thienyl)ethoxy)benzoyl)-2-methylindole-4-acetic Acid

231

[0316] TLC: Rf 0.50 (chloroform:methanol=10:1);

[0317] NMR (CDCl3): δ 7.69 (d, J=8.6 Hz, 2H), 7.18 (m, 1H), 7.02-6.90 (m, 7H), 6.47 (s, 1H), 4.26 (t, J=6.8 Hz, 2H), 3.84 (s, 2H), 3.35 (t, J=6.8 Hz, 2H), 2.43 (s, 3H).

Example 1(24)

[0318] 1-(4-(2-(2-Methylphenyl)ethoxy)benzoyl)-2-methylindole-4-acetic Acid

232

[0319] TLC: Rf 0.50 (chloroform:methanol=9:1);

[0320] NMR (CDCl3): δ 7.69 (d, J=9.0 Hz, 2H), 7.23-6.91 (m, 9H), 6.48 (s, 1H), 4.23 (t, J=7.2 Hz, 2H), 3.86 (s, 2H), 3.16 (t, J=7.2 Hz, 2H), 2.44 (s, 3H), 2.39 (s, 3H).

Example 1(25)

[0321] 1-(4-(2-(3-Methylphenyl)ethoxy)benzoyl)-2-methylindole-4-acetic Acid

233

[0322] TLC: Rf 0.50 (chloroform:methanol=9:1);

[0323] NMR (CDCl3): δ 7.69 (d, J=8.8 Hz, 2H), 7.19-6.92 (m, 9H), 6.48 (s, 1H), 4.24 (t, J=7.2 Hz, 2H), 3.86 (s, 2H), 3.10 (t, J=7.2 Hz, 2H), 2.44 (s, 3H), 2.36 (s, 3H).

Example 1(26)

[0324] 1-(4-(2-(4-Methylphenyl)ethoxy)benzoyl)-2-methylindole-4-acetic Acid

234

[0325] TLC: Rf 0.50 (chloroform:methanol=9:1);

[0326] NMR (CDCl3): δ 7.69 (d, J=8.8 Hz, 2H), 7.18-6.92 (m, 9H), 6.49 (s, 1H), 4.23 (t, J=6.6 Hz, 2H), 3.87 (s, 2H), 3.10 (t, J=6.6 Hz, 2H), 2.44 (s, 3H), 2.34 (s, 3H).

Example 1(27)

[0327] 1-(4-(2-Cyclohexylethoxy)benzoyl)-2-methylindole-4-acetic Acid

235

[0328] TLC: Rf 0.50 (chloroform:methanol=9:1);

[0329] NMR (CDCl3): δ 7.70 (d, J=8.8 Hz, 2H), 7.06-6.91 (m, 5H), 6.48 (s, 1H), 4.08 (t, J=6.8 Hz, 2H), 3.86 (s, 2H), 2.44 (s, 3H), 1.81-0.95 (m, 13H).

Example 1(28)

[0330] 1-(4-(2-(4-Dimethylaminophenyl)ethoxy)benzoyl)-2-methylindole-4-acetic Acid

236

[0331] TLC: Rf 0.50 (chloroform methanol=9:1);

[0332] NMR (CDCl3): δ 7.69 (d, J=8.6 Hz, 2H), 7.17 (d, J=8.6 Hz, 2H), 7.06-6.92 (m, 5H), 6.73 (d, J=8.6 Hz, 2H), 6.48 (s, 1H), 4.20 (t, J=7.4 Hz, 2H), 3.86 (s, 2H), 3.04 (t, J=7.4 Hz, 2H), 2.93 (s, 6H), 2.44 (s, 3H).

Example 1(29)

[0333] 1-(4-(2-(3-Thienyl)ethoxy)benzoyl)-2-methylindole-4-acetic Acid

237

[0334] TLC: Rf 0.50 (chloroform:methanol=10:1);

[0335] NMR (CDCl3): δ 7.69 (d, J=9.0 Hz, 2H), 7.30 (dd, J=4.0, 3.0 Hz, 1H), 7.11 (m, 1H), 7.06-7.01 (m, 2H), 6.96-6.92 (m, 4H), 6.48 (s, 1H), 4.25 (t, J=6.6 Hz, 2H), 3.85 (s, 2H), 3.17 (t, J=6.6 Hz, 2H), 2.43 (s, 3H).

Example 1(30)

[0336] 1-(4-(2-(4-Chlorophenyl)ethoxy)benzoyl)-2-methylindole-4-acetic Acid

238

[0337] TLC: Rf 0.45 (chloroform:methanol=10:1);

[0338] NMR (CDCl3): δ 7.69 (d, J=8.4 Hz, 2H), 7.33-7.20 (m, 5H), 7.04-6.82 (m, 4H), 6.49 (s, 1H), 4.23 (t, J=6.6 Hz, 2H), 3.86 (s, 2H), 3.11 (t, J=6.6 Hz, 2H), 2.44 (s, 3H).

Example 1(31)

[0339] 1-(4-(2-(2-Fluorophenyl)ethoxy)benzoyl)-2-methylindole-4-acetic Acid

239

[0340] TLC: Rf 0.45 (chloroform:methanol=10:1);

[0341] NMR (CDCl3): δ 7.68 (d, J=8.8 Hz, 2H), 7.40-7.08 (m, 4H), 7.05-6.90 (m, 5H), 6.47 (s, 1H), 4.26 (t, J=6.8 Hz, 2H), 3.84 (s, 2H), 3.18 (t, J=6.8 Hz, 2H), 2.43 (s, 3H).

Example 1(32)

[0342] 1-(4-(2-(4-Fluorophenyl)ethoxy)benzoyl)-2-methylindole-4-acetic Acid

240

[0343] TLC: Rf 0.45 (chloroform:methanol=10:1);

[0344] NMR (CDCl3): δ 7.70 (d, J=9.0 Hz, 2H), 7.30-7.21 (m, 2H), 7.06-6.90 (m, 7H), 6.48 (s, 1H), 4.23 (t, J=6.6 Hz, 2H), 3.85 (s, 2H), 3.11 (t, J=6.6 Hz, 2H), 2.43 (s, 3H).

Example 1(33)

[0345] 1-(4-(2-(2-Naphthyl)ethoxy)benzoyl)-2-methylindole-4-acetic Acid

241

[0346] TLC: Rf 0.47 (chloroform:methanol=9:1);

[0347] NMR (CDCl3): δ 7.86-6.90 (m, 14H), 6.49 (s, 1H), 4.35 (t, J=7.2 Hz, 2H), 3.86 (s, 2H), 3.31 (t, J=7.2 Hz, 2H), 2.43 (s, 3H).

Example 1(34)

[0348] 1-(4-(2-(4-Cyanophenyl)ethoxy)benzoyl)-2-methylindole-4-acetic Acid

242

[0349] TLC: Rf 0.40 (chloroform:methanol=9:1);

[0350] NMR (CDCl3): δ 7.70 (d, J=8.8 Hz, 2H), 7.63 (d, J=8.2 Hz, 2H), 7.42 (d, J=8.2 Hz, 2H), 7.03-6.90 (m, 5H),6.48 (s, 1H), 4.28 (t, J=6.4 Hz, 2H), 3.85 (s, 2H), 3.20 (t, J=6.4 Hz, 2H), 2.43 (s, 3H).

Example 1(35)

[0351] 1-(4-(2-t-Butoxyethoxy)benzoyl)-2-methylindole-4-acetic Acid

243

[0352] TLC: Rf 0.50 (chloroform:methanol=9:1);

[0353] NMR (CDCl3): δ 7.69 (d, J=8.8 Hz, 2H), 7.04-6.94 (m, 5H), 6.48 (s, 1H), 4.17 (t, J=5.2 Hz, 2H), 3.86 (s, 2H), 3.76 (t, J=5.2 Hz, 2H), 2.44 (s, 3H), 1.25 (s, 9H).

Example 1(36)

[0354] 1-(4-(2-(2-Methoxyphenyl)ethoxy)benzoyl)-2-methylindole-4-acetic Acid

244

[0355] TLC: Rf 0.45 (chloroform:methanol=10:1);

[0356] NMR (CDCl3): δ 7.69 (d, J=8.8 Hz, 2H), 7.22 (d, J=7.2 Hz, 2H), 7.04-6.93 (m, 7H), 6.47 (s, 1H), 4.24 (t, J=7.4 Hz, 2H), 3.85 (s, 2H), 3.85 (s, 3H), 3.14 (t, J=7.4 Hz, 2H), 2.43 (s, 3H).

Example 1(37)

[0357] 1-(3-Propoxybenzoyl)-2-methylindole-4-acetic Acid

245

[0358] TLC: Rf 0.47 (chloroform:methanol=10:1);

[0359] NMR (CDCl3): δ 7.40-6.99 (m, 7H), 6.48 (s, 1H), 3.94 (t, J=6.6 Hz, 2H), 3.85 (s, 2H), 2.41 (s, 3H), 1.81 (m, 2H), 1.03 (t, J=7.4 Hz, 3H).

Example 1(38)

[0360] 1-(4-(2-(3-Pyridyl)ethoxy)benzoyl)-2-methylindole-4-acetic Acid

246

[0361] TLC: Rf 0.30 (chloroform:methanol=9:1);

[0362] NMR (CDCl3): δ 8.61 (s, 1H), 8.54 (dd, J=3.0 Hz, 1H), 7.71-7.67 (m, 3H), 7.34-7.31 (m, 1H), 7.05-6.89 (m, 5H), 6.52 (s, 1H), 4.25 (t, J=6.4 Hz, 2H), 3.87 (s, 2H), 3.14 (t, J=6.4 Hz, 2H), 2.42 (s, 3H).

Example 1(39)

[0363] 1-(4-(2-(4-Pyridyl)ethoxy)benzoyl)-2-methylindole-4-acetic Acid

247

[0364] TLC: Rf 0.30 (chloroform:methanol=9:1);

[0365] NMR (CDCl3): δ 8.57 (d, J=6.2 Hz, 2H), 7.70 (d, J=8.8 Hz, 2H), 7.29 (m, 2H), 7.04-6.89 (m, 5H), 6.52 (s, 1H), 4.28 (t, J=6.4 Hz, 2H), 3.86 (s, 2H), 3.15 (t, J=6.4 Hz, 2H), 2.42 (s, 3H).

Example 1(40)

[0366] 1-(4-(2-(1-Naphthyl)ethoxy)benzoyl)-2-methylindole-4-acetic Acid

248

[0367] TLC: Rf 0.47 (chloroform:methanol=9:1);

[0368] NMR (CDCl3): δ 8.13-8.08 (m, 1H), 7.92-7.87 (m, 1H), 7.83-7.75 (m, 1H), 7.69 (d, J=8.7 Hz, 2H), 7.61-7.47 (m, 2H), 7.48-7.41 (m, 2H), 7.07-6.90 (m, 5H), 6.48 (s, 1H), 4.39 (t, J=7.5 Hz, 2H), 3.87 (s, 2H), 3.63 (t, J=7.5 Hz, 2H), 2.43 (s, 3H).

Example 1(41)

[0369] 1-(4-(3-Ethoxypropoxy)-3-methoxybenzoyl)-2-methylindole-4-acetic Acid

249

[0370] TLC: Rf 0.55 (chloroform:methanol=10:1);

[0371] NMR (CDCl3): δ 7.34 (d, J=1.8 Hz, 1H), 7.27 (dd, J=8.4, 1.8 Hz, 1H), 7.10-6.93 (m, 3H), 6.89 (d, J=8.4 Hz, 1H), 6.48 (s, 1H), 4.19 (t, J=6.4 Hz, 2H), 3.85 (s, 3H), 3.83 (s, 2H), 3.62 (t, J=5.8 Hz, 2H), 3.50 (q, J=6.8 Hz, 2H), 2.44 (s, 3H), 2.13 (m, 2H), 1.19 (t, J=6.8 Hz, 3H).

Example 1(42)

[0372] 1-(4-Hexyloxybenzoyl)-2-methylindole-4-acetic Acid

250

[0373] TLC: Rf 0.44 (ethyl acetate);

[0374] NMR (CDCl3): δ 7.72-7.69 (m, 2H), 7.06-6.93 (m, 5H), 6.49 (s, 1H), 4.04 (t, J=6.5 Hz, 2H), 3.87 (s, 2H), 2.45 (s, 3H), 1.9-1.8 (m, 2H), 3.87 (s, 2H), 2.45 (s, 3H), 1.9-1.8 (m, 2H), 1.6-1.4 (m, 2H), 1.4-1.3 (m, 4H), 1.0-0.9 (m, 3H).

Example 1(43)

[0375] 1-(4-Butoxybenzoyl)-3-(4-methoxybenzyl)-2-methylindole-4-acetic Acid

251

[0376] TLC: Rf 0.43 (ethyl acetate);

[0377] NMR (CDCl3): δ 7.75-7.72 (m, 2H), 7.11-6.92 (m, 7H), 6.82-6.79 (m, 2H), 4.15 (s, 2H), 4.05 (t, J=6.5 Hz, 2H), 3.76 (s, 3H), 3.72 (s, 2H), 2.35 (s, 3H), 1.9-1.7 (m, 2H), 1.6-1.4 (m, 2H), 1.00 (t, J=7.0 Hz, 3H).

Example 1(44)

[0378] 1-(4-(2-(2-Methoxyethoxy)ethoxy)benzoyl)-2-methylindole-4-acetic Acid

252

[0379] TLC: Rf 0.20 (ethyl acetate);

[0380] NMR (CDCl3): δ 7.71-7.68 (m, 2H), 7.06-6.91 (m, 5H), 6.48 (s, 1H), 4.24-4.21 (m, 2H), 3.92-3.89 (m, 2H), 3.85 (s, 2H), 3.76-3.73 (m, 2H), 3.61-3.58 (m, 2H), 3.40 (s, 3H), 2.44 (s, 3H).

Example 1(45)

[0381] 1-(4-(3-Methoxypropyloxy)benzoyl)-2-methylindole-4-acetic Acid

253

[0382] TLC: Rf 0.12 (ethyl acetate);

[0383] NMR (CDCl3): δ 7.72-7.69 (m, 2H), 7.08-6.94 (m, 5H), 6.48 (s, 1H), 4.15 (t, J=6.5 Hz, 2H), 3.86 (s, 2H), 3.58 (t, J=6.0 Hz, 2H), 3.37 (s, 3H), 2.44 (s, 3H), 2.13-2.05 (m, 2H).

Example 1(46)

[0384] 1-(4-Methoxybenzoyl)-2-methylindole-4-acetic Acid

254

[0385] TLC: Rf 0.41 (chloroform:methanol=9:1);

[0386] NMR (CDCl3): δ 7.72 (d, J=9.0 Hz, 2H), 7.08-6.92 (m, 5H), 6.50 (s, 1H), 3.90 (s, 3H), 3.88 (s, 2H), 2.45 (s, 3H).

Example 1(47)

[0387] 1-(4-(5-Methylfuran-2-yl)methoxybenzoyl)-2-methylindole-4-acetic Acid

255

[0388] TLC: Rf 0.40 (chloroform:methanol=10:1);

[0389] NMR (CDCl3): δ 7.72 (d, J=8.6 Hz, 2H), 7.07-6.95 (m, 5H), 6.49 (s, 1H), 6.36 (d, J=3.2 Hz, 1H), 5.99 (d, J=3.2 Hz, 1H), 5.02 (s, 2H), 3.86 (s, 2H), 2.44 (s, 3H), 2.32 (s, 3H).

Example 1(48)

[0390] 1-(4-(2-Methoxyethoxy)benzoyl)-2-methylindole-4-acetic Acid

256

[0391] TLC: Rf 0.44 (chloroform:methanol=10:1);

[0392] NMR (CDCl3): δ 7.70 (d, J=8.8 Hz, 2H), 7.03-6.93 (m, 5H), 6.48 (s, 1H), 4.21 (t, J=5.0 Hz, 2H), 3.85 (s, 2H), 3.79 (t, J=5.0 Hz, 2H), 3.47 (s, 3H), 2.44 (s, 3H).

Example 1(49)

[0393] 1-(4-(2-(3-Nitrophenyl)ethoxy)benzoyl)-2-methylindole-4-acetic Acid

257

[0394] TLC: Rf 0.37 (chloroform:methanol=9:1);

[0395] NMR (CDCl3): δ 8.22-8.16 (m, 1H), 8.16-8.10 (m, 1H), 7.74-7.62 (m, 3H), 7.52 (t, J=8.1 Hz, 1H), 7.08-6.90 (m, 5H), 6.49 (s, 1H), 4.31 (t, J=6.3 Hz, 2H), 3.87 (s, 2H), 3.26 (t. J=6.3 Hz, 2H), 2.43 (s, 3H).

Example 1(50)

[0396] 1-(4-(3-Phenylpropoxy)benzoyl)-2-methylindole-4-acetic Acid

258

[0397] TLC: Rf 0.41 (chloroform:methanol=9:1);

[0398] NMR (CDCl3): δ 7.70 (d, J=9.3 Hz, 2H), 7.34-7.16 (m, 5H), 7.08-6.88 (m, 5H), 6.50 (s, 1H), 4.05 (t, J=6.3 Hz, 2H), 3.88 (s, 2H), 2.84 (t, J=6.3 Hz, 2H), 2.45 (s, 3H), 2.20-2.10 (m, 2H).

Example 1(51)

[0399] (+)-1-(4-(3-Phenyloxy-2-hydroxypropyloxy)benzoyl)-2-methylindole-4-acetic Acid

259

[0400] TLC: Rf 0.33 (chloroform:methanol=10:1);

[0401] NMR (CDCl3): δ 7.69 (d, J=8.8 Hz, 2H), 7.33-7.23 (m, 2H), 7.06-6.90 (m, 8H), 6.47 (s, 1H), 4.43 (m, 1H), 4.24-4.15 (m, 4H), 3.83 (s, 2H), 2.42 (s, 3H).

Example 1(52)

[0402] 1-(4-Cyclohexyloxybenzoyl)-2-methylindole-4-acetic Acid

260

[0403] TLC: Rf 0.25 (ethyl acetate);

[0404] NMR (CDCl3): δ 7.71-7.68 (m, 2H), 7.08-6.91 (m, 5H), 6.49 (s, 1H), 4.42-4.32 (m, 1H), 3.86 (s, 2H), 2.45(s, 3H), 2.08-1.96 (m, 2H), 1.88-1.78 (m, 2H), 1.64-1.32 (m, 6H).

Example 1(53)

[0405] 1-(4-Ethoxybenzoyl)-2-methylindole-4-acetic Acid

261

[0406] TLC: Rf 0.21 (ethyl acetate);

[0407] NMR (CDCl3): δ 7.72-7.69 (m, 2H), 7.08-6.93 (m, 5H), 6.49 (s, 1H), 4.10 (q, J=7.0 Hz, 2H), 3.86 (s, 2H), 2.45 (s, 3H), 1.46 (t, J=7.0 Hz, 3H).

Example 1(54)

[0408] 1-(4-(3-Butenyloxy)benzoyl)-2-methylindole-4-acetic Acid

262

[0409] TLC: Rf 0.28 (ethyl acetate);

[0410] NMR (CDCl3): δ 7.72-7.69 (m, 2H), 7.08-6.94 (m, 5H), 6.49 (s, 1H), 5.98-5.85 (m, 1H), 5.23-5.13 (m, 2H), 4.10 (t, J=6.5 Hz, 2H), 3.86 (s, 2H), 2.64-2.56 (m, 2H), 2.45 (s, 3H).

Example 1(55)

[0411] 1-(4-(2-(2,6-Dimethoxyphenyl)ethoxy)benzoyl)-2-methylindole-4-acetic Acid

263

[0412] TLC: Rf 0.26 (ethyl acetate);

[0413] NMR (CDCl3): δ 7.71-7.68 (m, 2H), 7.20 (t, J=8.5 Hz, 1H), 7.07-6.98 (m, 5H), 6.57 (d, J=8.5 Hz, 2H), 6.48 (s, 1H), 4.17-4.11 (m, 2H), 3.87 (s, 2H), 3.84 (s, 6H), 3.23-3.18 (m, 2H), 2.45 (s, 3H).

Example 1(56)

[0414] 1-(4-Butoxybenzoyl)-2,3-dimethylindole-4-acetic Acid

264

[0415] TLC: Rf 0.44 (chloroform:methanol=10:1);

[0416] NMR (CDCl3): δ 7.72-7.65 (m, 2H), 7.07-6.90 (m, 5H), 4.07 (s, 2H), 4.04 (t, J=6.4 Hz, 2H), 2.39 (s, 3H), 2.30 (s, 3H), 1.87-1.74 (m, 2H), 1.60-1.41 (m, 2H), 0.99 (t, J=7.4 Hz, 3H).

Example 1(57)

[0417] 1-(3-Butoxybenzoyl)-2-methylindole-4-acetic Acid

265

[0418] TLC: Rf 0.48 (chloroform:methanol=10:1);

[0419] NMR (CDCl3): δ 7.36 (m, 1H), 7.24-6.99 (m, 6H), 6.48 (d, J=1.2 Hz, 1H), 3.98 (t, J=6.4 Hz, 2H), 3.85 (s, 2H), 2.41 (d, J=1.2 Hz, 3H), 1.84-1.70 (m, 2H), 1.58-1.38 (m, 2H), 0.96 (t, J=7.2 Hz, 3H).

Example 1(58)

[0420] 1-(3-Pentyloxybenzoyl)-2-methylindole-4-acetic Acid

266

[0421] TLC: Rf 0.47 (chloroform:methanol=10:1);

[0422] NMR (CDCl3): δ 7.35 (m, 1H), 7.24-6.99 (m, 6H), 6.48 (d, J=1.0 Hz, 1H), 3.97 (t, J=6.4 Hz, 2H), 3.85 (s, 2H), 2.41 (d, J=1.0 Hz, 3H), 1.84-1.72 (m, 2H), 1.50-1.32 (m, 4H), 0.92 (t, J=7.0 Hz, 3H).

Example 1(59)

[0423] 1-(3-Hexyloxybenzoyl)-2-methylindole-4-acetic Acid

267

[0424] TLC: Rf 0.46 (chloroform:methanol=10:1);

[0425] NMR (CDCl3): δ 7.35 (m, 1H), 7.24-6.98 (m, 6H), 6.48 (d, J=1.0 Hz, 1H), 3.97 (t, J=6.6 Hz, 2H), 3.85 (s, 2H), 2.41 (d, J=1.0 Hz, 3H), 1.85-1.69 (m, 2H), 1.53-1.28 (m, 6H), 0.90 (m, 3H).

Example 1(60)

[0426] 1-(3-Benzyloxybenzoyl)-2-methylindole-4-acetic Acid

268

[0427] TLC: Rf 0.46 (chloroform:methanol=10:1);

[0428] NMR (CDCl3): δ 7.44-7.18 (m, 9H), 7.10-6.99 (m, 3H), 6.48 (d, J=1.0 Hz, 1H), 5.08 (s, 2H), 3.85 (s, 2H), 2.36 (d, J=1.0 Hz, 3H).

Example 1(61)

[0429] 1-(3-Phenethyloxybenzoyl)-2-methylindole-4-acetic Acid

269

[0430] TLC: Rf 0.46 (chloroform methanol=10:1);

[0431] NMR (CDCl3): δ 7.39-6.97 (m, 12H), 6.48 (d, J=1.2 Hz, 1H), 4.20 (t, J=7.0 Hz, 2H), 3.85 (s, 2H), 3.09 (t, J=7.0 Hz, 2H), 2.40 (d, J=1.2 Hz, 3H).

Example 1(62)

[0432] 1-(3-(3-Phenylpropyloxy)benzoyl)-2-methylindole-4-acetic Acid

270

[0433] TLC: Rf 0.47 (chloroform:methanol=10:1);

[0434] NMR (CDCl3): δ 7.40-6.98 (m, 12H), 6.48 (d, J=1.0 Hz, 1H), 3.98 (t, J=6.2 Hz, 2H), 3.85 (s, 2H), 2.80 (t, J=7.2 Hz, 2H), 2.41 (d, J=1.0 Hz, 3H), 2.17-2.03 (m, 2H).

Example 1(63)

[0435] 1-(4-(2-(2-Trifluoromethylphenyl)ethoxy)benzoyl)-2-methylindole-4-acetic Acid

271

[0436] TLC: Rf 0.46 (chloroform:methanol=9:1);

[0437] NMR (CDCl3): δ 7.73-7.65 (m, 3H), 7.56-7.45 (m, 2H), 7.42-7.33 (m, 1H), 7.08-6.90 (m, 5H), 6.49 (s, 1H), 4.27 (t, J=6.6 Hz, 2H), 3.87 (s, 2H), 3.34 (t, J=6.6 Hz, 2H), 2.44 (s, 3H).

Example 1(64)

[0438] 1-(4-(2-(2-Trifluoromethylphenyl)ethoxy)benzoyl)-2-methyl-3-methoxymethylindole-4-acetic Acid

272

[0439] TLC: Rf 0.56 (chloroform:methanol=9:1);

[0440] NMR (CDCl3): δ 7.74-7.65 (m, 3H), 7.57-7.45 (m, 2H), 7.42-7.30 (m, 1H), 7.14-7.10 (m, 1H), 7.05-6.80 (m, 1H), 6.98-6.90 (m, 3H), 4.71 (s, 2H), 4.27 (t, J=6.6 Hz, 2H), 4.09 (s, 2H), 3.47 (s, 3H), 3.34 (t, J=6.6 Hz, 2H), 2.46 (s, 3H).

Example 1(65)

[0441] 1-(4-(2-(3-N itrophenyl)ethoxy)benzoyl)-2-methyl-3-methoxymethylindole-4-acetic Acid

273

[0442] TLC: Rf 0.54 (chloroform:methanol=9:1);

[0443] NMR (CDCl3): δ 8.22-8.18 (m, 1H), 8.16-8.11 (m, 1H), 7.71 (d, J=8.7 Hz, 2H), 7.68-7.60 (m, 1H), 7.52 (t, J=7.8 Hz, 1H), 7.14-7.09 (m, 1H), 7.00 (t, J=8.1 Hz, 1H), 6.97-6.90 (m, 3H), 4.70 (s, 2H), 4.32 (t, J=6.3 Hz, 2H), 4.09 (s, 2H), 3.46 (s, 3H), 3.26 (t, J=6.3 Hz, 2H), 2.45 (s, 3H).

Example 1(66)

[0444] 1-(4-(2-Phenoxyethyl)benzoyl)-2-methylindole-4-acetic Acid

274

[0445] TLC: Rf 0.45 (chloroform:methanol=10:1);

[0446] NMR (CDCl3): δ 7.64 (d, J=8.4 Hz, 2H), 7.36 (d, J=8.4 Hz, 2H), 7.24 (d, J=8.0 Hz, 2H), 7.03-6.85 (m, 6H), 6.47 (s, 1H), 4.20 (t, J=6.6 Hz, 2H), 3.81 (s, 2H), 3.15 (t, J=6.6 Hz, 2H), 2.39 (s, 3H).

Example 1(67)

[0447] (+)-1-(4-(2-Phenyl-2-hydroxyethoxy)benzoyl)-2-methylindole-4-acetic Acid

275

[0448] TLC: Rf 0.33 (chloroform:methanol=10:1);

[0449] NMR (CDCl3): δ 7.57 (d, J=8.2 Hz, 2H), 7.32 (s, 5H), 6.99 (m, 1H), 6.93-6.86 (m, 4H), 6.44 (s, 1H), 5.34 (dd, J=8.0, 3.6 Hz, 1H), 3.97 (dd, J=12.2, 8.0 Hz, 1H), 3.86 (dd, J=12.2, 3.6 Hz, 1H), 3.81 (s, 2H), 2.37 (s, 3H).

Example 1(68)

[0450] 1-(4-(2-(3-Aminophenyl)ethoxy)benzoyl)-2-methylindole-4-acetic Acid

276

[0451] TLC: Rf 0.47 (chloroform:methanol=9:1);

[0452] NMR (CDCl3): δ 7.70 (d, J=9.0 Hz, 2H), 7.16-6.90 (m, 6H), 6.72-6.67 (m, 1H), 6.65-6.56 (m, 2H), 6.49 (s, 1H), 4.23 (t, J=7.2 Hz, 2H), 3.87 (s, 2H), 3.05 (t, J=7.2 Hz, 2H), 2.45 (s, 3H).

Example 1(69)

[0453] 1-(4-(2-(3-Aminophenyl)ethoxy)benzoyl)-2-methyl-3-methoxymethylindole-4-acetic Acid

277

[0454] TLC: Rf 0.53 (chloroform:methanol=9:1);

[0455] NMR (CDCl3): δ 7.70 (d, J=9.0 Hz, 2H), 7.16-7.08 (m, 2H), 7.01 (t, J=8.4 Hz, 1H), 6.97-6.90 (m, 3H), 6.71-6.66 (m, 1H), 6.64-6.56 (m, 2H), 4.70 (s, 2H), 4.23 (t, J=7.2 Hz, 2H), 4.09 (s, 2H), 3.46 (s, 3H), 3.05 (t, J=7.2 Hz, 2H), 2.46 (s, 3H).

Example 1(70)

[0456] 1-(4-Butoxybenzoyl)-2-ethylindole-4-acetic Acid

278

[0457] TLC: Rf 0.55 (chloroform:methanol=9:1);

[0458] NMR (CDCl3): δ 7.71 (d, J=8.7 Hz, 2H), 7.07-6.86 (m, 5H), 6.53 (s, 1H), 4.05 (t, J=6.3 Hz, 2H), 3.89 (s, 2H), 2.87 (q, J=7.5 Hz, 2H), 1.90-1.35 (m, 4H), 1.24 (t, J=7.5 Hz, 3H), 0.97 (t, J=7.5 Hz, 3H).

Example 1(71)

[0459] 1-(4-(2-Phenoxyethoxy)benzoyl)-2-methylindole-4-acetic Acid

279

[0460] TLC: Rf 0.55 (chloroform:methanol=9:1);

[0461] NMR (CDCl3): δ 7.72 (d, J=9.0 Hz, 2H), 7.32 (t, J=7.8 Hz, 2H), 7.08-6.92 (m, 8H), 6.49 (s, 1H), 4.46-4.34 (m, 4H), 3.87 (s, 2H), 2.45 (s, 3H).

Example 1(72)

[0462] (±)-1-(4-(2-Methoxy-2-phenylethoxy)benzoyl)-2-methylindole-4-acetic Acid

280

[0463] TLC: Rf 0.52 (chloroform:methanol=10:1);

[0464] NMR (CDCl3): δ 7.59 (d, J=9.0 Hz, 2H), 7.38-7.30 (m, 5H), 7.04-6.80 (m, 5H), 6.44 (s, 1H), 5.44 (dd, J=8.0, 4.0 Hz, 1H), 3.84 (dd, J=10.8, 8.0 Hz, 1H), 3.83 (brs, 2H), 3.65 (dd, J=10.8, 4.0 Hz, 1H), 3.47 (s, 3H), 2.39 (s, 3H).

Example 1(73)

[0465] 1-(4-Phenylbenzoyl)-2-methylindole-4-acetic Acid

281

[0466] TLC: Rf 0.50 (chloroform:methanol=10:1);

[0467] NMR (CDCl3): δ 7.84-7.78 (m, 2H), 7.74-7.66 (m, 4H), 7.52-7.38 (m, 3H), 7.10-6.98 (m, 3H), 6.52 (s, 1H), 3.87 (s, 2H), 2.46 (s, 3H).

Example 1(74)

[0468] 1-(4-Phenyldiazobenzoyl)-2-methylindole-4-acetic Acid

282

[0469] TLC: Rf 0.50 (chloroform:methanol=10:1);

[0470] NMR (CDCl3) δ 8.04-7.96 (m, 4H), 7.90-7.86 (m, 2H), 7.60-7.52 (m, 3H), 7.10-7.00(m, 3H), 6.53 (s, 1H), 3.87 (s, 2H), 2.46 (s, 3H).

Example 1(75)

[0471] 1-(4-Butoxybenzoyl)-2,5-dimethylindole-4-acetic Acid

283

[0472] TLC: Rf 0.53 (chloroform:methanol=10:1);

[0473] NMR (CDCl3): δ 7.68 (d, J=9.3 Hz, 2H), 6.93 (d, J=9.3 Hz, 2H), 6.85 (d, J=9.0 Hz, 1H), 6.82 (d, J=9.0 Hz, 1H), 6.44 (s, 1H), 4.04 (t, J=6.6 Hz, 2H), 3.86 (s, 2H), 2.43 (s, 3H), 2.37 (s, 3H), 1.80 (m, 2H), 1.53 (m, 2H), 0.99 (t, J=7.5 Hz, 3H).

REFERENCE EXAMPLE 9

[0474] 2-Methylindole-4-carboxylic Acid Methyl Ester

284

[0475] To a solution of 2-methyl-4-trifluoromethanesulfoxyindole (6.32 g; prepared in Reference Example 1) in methanol (33.43 ml)—N,N-dimethylformamide (200 ml) was added triethylamine (6.3 ml) and tetrakis(triphenylphosphine)palladium (2.6 g). The inside of the vessel was replaced with carbon monoxide and the mixture was stirred at 60° C. overnight. After the reaction was completed, to the mixture was added water and ethyl acetate and then the mixture was extracted. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with water and a saturated aqueous solution of sodium chloride, successively, dried and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane—ethyl acetate) to give the title compound (4.29 g) having the following physical data.

[0476] TLC: Rf 0.18 (toluene).

REFERENCE EXAMPLE 10

[0477] 2-Methylindole-4-carboxylic Acid

285

[0478] To a solution of 2-methylindole-4-carboxylic acid methyl ester (4.3 g; prepared in Reference Example 9) in methanol—dioxane (10 ml+10 ml) was added 5N aqueous solution of sodium hydroxide (10 ml), and the mixture was stirred at 60° C. overnight. To the reaction solution was added 2N hydrochloric acid, and then extracted with ethyl acetate. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with water and a saturated aqueous solution of sodium chloride, successively, dried and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (chloroform-methanol) to give the title compound (1.6 g) having the following physical data.

[0479] TLC: Rf 0.48(chloroform:methanol=9:1);

[0480] NMR (CDCl3): δ 8.14-8.04 (br, 1H), 7.93 (dd, 1H), 7.52 (m, 1H), 7.18 (dd, 1H), 6.94 (m, 1H), 3.71 (s, 3H).

REFERENCE EXAMPLE 11

[0481] 2-Methylindole-4-carboxylic Acid Benzyl Ester

286

[0482] To a solution of 2-methylindole-4-carboxylic acid (690 mg; prepared in Reference Example 10) in N,N-dimethylformamide (10 ml) was added anhydrous potassium carbonate (815 mg) and benzyl bromide (0.7 ml) at room temperature, and the mixture was stirred at 80° C. for 2 hours. To the reaction solution was added water and ethyl acetate, and then extracted. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with water and a saturated aqueous solution of sodium chloride, successively, dried and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (hexane—ethyl acetate) to give the title compound (610 mg) having the following physical data.

[0483] TLC: Rf 0.44(hexane:ethyl acetate=8:2);

[0484] NMR (CDCl3): δ 8.05 (brs, 1H), 7.91 (d, 1H), 7.54-7.24 (m, 7H), 6.88 (m, 1H), 5.44 (s, 2H), 2.48 (s, 3H).

REFERENCE EXAMPLE 12

[0485] 1-(4-Butoxybenzoyl)-2-methylindole-4-carboxylic Acid Benzyl Ester

287

[0486] To a solution of 2-methylndole-4-carboxylic acid benzyl ester (690 mg; prepared in Reference Example 11) in N,N-dimethylformamide (8 ml) was added sodium hydride (114 mg; 60%) at 0° C., and the mixture was stirred at the same temperature for 30 minutes. To the reaction mixture was added 4-butoxybenzoyl chloride (0.54 ml), and the mixture was stirred at room temperature overnight. To the reaction mixture was added water and ethyl acetate, and then separated. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with water and a saturated aqueous solution of sodium chloride, successively, dried and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (hexane—ethyl acetate) to give the title compound (1.02 g) having the following physical data.

[0487] TLC: Rf 0.61 (hexane:ethyl acetate=8:2);

[0488] NMR (CDCl3): δ 8.10-6.90 (m, 13H), 5.45 (s, 2H), 4.05 (t, 2H), 2.44 (s, 3H), 1.86-1.74 (m, 2H), 1.60-1.45 (m, 2H), 0.99 (t, 3H).

EXAMPLE 2

[0489] (1) 1-(4-Butoxybenzoyl)-2-methylndole-4-carboxylic acid and (2) 1-(4-Butoxybenzoyl)-2-methyl-2,3-dihydroindole-4-carboxylic Acid

288

[0490] To a solution of 1-(4-butoxybenzoyl)-2-methylndole-4-carboxylic acid benzyl ester (1.02 g; prepared in Reference Example 12) in methanol (10 ml)—ethyl acetate (5 ml) was added palladium on activated carbon (100 mg). The inside of the vessel was replaced with hydrogen and the mixture was stirred at room temperature overnight. The reaction mixture was filtered through Celite (trademark). The filtrate and washing with chloroform were combined, and then concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (chloroform—methanol) to give the title compound having the following physical data.

[0491] (1) indole

[0492] TLC: Rf 0.59 (chloroform:methanol=9:1);

[0493] NMR (CDCl3): δ 7.99 (d, J=8.1 Hz, 1H), 7.70 (d, J=9.0 Hz, 2H), 7.36 (d, J=8.1 Hz, 1H), 7.21 (brs, 1H), 7.13 (t, J=8.1 Hz, 1H), 6.97 (d, J=9.0 Hz, 2H), 4.06 (t, J=6.6 Hz, 2H), 2.48 (s, 3H), 1.88-1.76 (m, 2H), 1.60-1.46 (m, 2H), 1.00 (t, J=7.5 Hz, 3H).

[0494] (2) indoline

[0495] TLC: Rf 0.53 chloroform:methanol=9:1);

[0496] NMR (CDCl3): δ 7.74 (dd, 1H), 7.64-7.46 (br, 1H), 7.50 (d, 2H), 7.19 (t, 1H), 6.93 (d, 2H), 4.84-4.70 (m, 1H), 4.02 (t, 2H), 3.65 (dd, 1H), 3.22 (dd, 1H), 1.86-1.76 (m, 2H), 1.60-1.45 (m, 2H), 1.24 (d, 3H), 1.00 (t, 3H).

REFERENCE EXAMPLE 13

[0497] 2-Methylindol-4-yloxyacetic Acid Methyl Ester

289

[0498] To a solution of 2-methyl-4-hydroxyindole (5 g) in N,N-dimethylformamide (50 ml) was added anhydrous potassium carbonate 11.7 g) and methyl bromoacetate (3.54 ml) at room temperature, and the mixture was stirred at 80° C. for 2 hours. To the reaction solution was added iced water to give the title compound (5.4 g) having the following physical data.

[0499] TLC: Rf 0.75 (benzene: ethyl acetate=4:1);

[0500] NMR (CDCl3): δ 8.00-7.84 (br, 1H), 7.04-6.94 (m, 2H), 6.45-5.36 (m, 2H), 4.77 (s, 2H), 3.80 (s, 3H), 2.43 (s, 3H).

REFERENCE EXAMPLE 14

[0501] 2-Methylindol-4-yloxyacetic Acid

290

[0502] To a solution of 2-methylindol-4-yloxyacetic acid methyl ester (5.4 g) in methanol (18 ml)—dioxane (36 ml) was added 5N aqueous solution of sodium hydroxide (15 ml), and the mixture was stirred at room temperature for 1 hour. To the reaction solution was added 2N hydrochloric acid to give the title compound (3.5 g) having the following physical data.

[0503] TLC: Rf 0.20(chloroform:methanol=9:1).

REFERENCE EXAMPLE 15

[0504] 2-Methylindol-4-yloxyacetic Acid Allyl Ester

291

[0505] To a solution of 2-methylindol-4-yloxyacetic acid (2 g) in N,N-dimethylformamide (20 ml) was added anhydrous potassium carbonate (2.02 g) and allyl bromide (1.27 ml), and the mixture was stirred at 80° C. for 2 hours. To the reaction mixture was added water and ethyl acetate, then separated. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with water and a saturated aqueous solution of sodium chloride, successively, dried and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane—ethyl acetate) to give the title compound (1.88 g) having the following physical data.

[0506] TLC: Rf 0.50(n-hexane:ethyl acetate=7:3).

REFERENCE EXAMPLE 16

[0507] 1-(4-Butoxybenzoyl)-2-methylindol-4-yloxyacetic Acid Allyl Ester

292

[0508] To a solution of 2-methylindol-4-yloxyacetic acid allyl ester (900 mg) in N,N-dimethylformamide (10 ml) was added sodium hydride (147 mg; 60%) at 0° C., and the mixture was stirred at the same temperature for 30 minutes. To the reaction mixture was added 4-butoxybenzoyl chloride (0.70 ml), and the mixture was stirred at room temperature overnight. To the reaction mixture was added water and ethyl acetate, and then separated. The aqueous layer was washed with ethyl acetate. The combined organic layer was washed with water and a saturated aqueous solution of sodium chloride, successively, dried and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (hexane—ethyl acetate) to give the title compound (800 mg) having the following physical data.

[0509] TLC: Rf 0.63(n-hexane:ethyl acetate=7:3);

[0510] NMR (CDCl3): δ 7.69 (d, 2H), 7.00-6.85 (m, 3H), 6.68 (d, 1H), 6.67 (s, 1H), 6.47 (d, 1H), 6.00-5.87 (m, 1H), 5.40-5.30 (m, 1H), 5.30-5.24 (m, 1H), 4.78 (s, 2H), 4.75-4.68 (m, 2H), 4.05 (t, 2H), 2.42 (s, 3H), 1.87-1.75 (m, 2H), 1.60-1.45 (m, 2H), 1.00 (t, 3H).

EXAMPLE 3

[0511] 1-(4-Butoxybenzoyl)-2-methylindol-4-yloxyacetic Acid

293

[0512] The compound of the present invention having the following physical data was obtained by the same procedure as Example 1, using the compound prepared in Reference Example 16.

[0513] TLC: Rf 0.38 (chloroform:methanol:acetic acid=90:9:1);

[0514] NMR (CDCl3): δ 7.70 (d, J=9.0 Hz, 2H), 6.98-6.89 (m, 3H), 6.71 (d, J=8.4 Hz, 1H), 6.60-6.57 (m, 1H), 6.51 (d, J=8.4 Hz, 1H), 4.84 (s, 2H), 4.05 (t, J=6.6 Hz, 2H), 2.43 (s, 3H), 1.87-1.75 (m, 2H), 1.59-1.44 (m, 2H), 1.00 (t, J=7.5 Hz, 3H).

EXAMPLES 3(1) TO 3(6)

[0515] Each compound having the following physical data was obtained by the same procedures as a series of reactions of Reference Examples 13, 14, 15, 16 and Example 3.

EXAMPLE 3(1)

[0516] 1-(4-(2-Ethoxyethoxy)benzoyl)-2-methylindolyl-4-oxyacetic Acid

294

[0517] TLC: Rf 0.19 (methylene chloride:methanol=9:1);

[0518] NMR (CDCl3): δ 7.68 (d, J=8.5 Hz, 2H), 6.97 (d, J=8.5 Hz, 2H), 6.91 (m, 1H), 6.66 (d, J=8.5 Hz, 1H), 6.58 (s, 1H), 6.49 (d, J=8.0 Hz, 1H), 4.77 (s, 2H), 4.20 (t, J=5.0 Hz, 2H), 3.83 (t, J=5.0 Hz, 2H), 3.62 (q, J=7.0 Hz, 2H), 2.41 (s, 3H), 1.26 (t, J=7.0 Hz, 3H).

EXAMPLE 3(2)

[0519] 1-(4-Propyloxybenzoyl)-2-methylindolyl-4-oxyacetic Acid

295

[0520] TLC: Rf 0.39 (chloroform:methanol=9:1);

[0521] NMR (CDCl3): δ 7.73-7.67 (m, 2H), 6.97-6.90 (m, 3H), 6.72 (d, J=8.4 Hz, 1H), 6.59 (s, 1H), 6.52 (d, J=7.5 Hz, 1H), 4.80 (s, 2H), 4.01 (t, J=6.6 Hz, 2H), 2.43 (s, 3H), 1.86 (dt, J=7.5, 6.6 Hz, 2H), 1.07 (t, J=7.5 Hz, 3H).

EXAMPLE 3(3)

[0522] 1-(4-Phenethyloxybenzoyl)-2-methylindolyl-4-oxyacetic Acid

296

[0523] TLC: Rf 0.35 (chloroform:methanol=9:1);

[0524] NMR (CDCl3): δ 7.71-7.67 (m, 2H), 7.37-7.25 (m, 5H), 6.97-6.89 (m, 3H),6.70 (d, J=8.4 Hz, 1H), 6.58 (s, 1H), 6.52 (d, J=8.1 Hz, 1H), 4.80 (s, 2H), 4.26 (t, J=6.9 Hz, 2H), 3.14 (t, J=6.9 Hz, 2H), 2.43 (s, 3H).

EXAMPLE 3(4)

[0525] 1-(4-Benzyloxybenzoyl)-2-methylindolyl-4-oxyacetic Acid

297

[0526] TLC: Rf 0.48 (chloroform:methanol=10:1);

[0527] NMR (DMSO-d6): δ 7.65 (d, J=8.8 Hz, 2H), 7.51-7.33 (m, 5H), 7.17 (d, J=8.8 Hz, 2H), 6.93 (t, J=8.2 Hz, 1H), 6.59-6.52 (m, 3H), 5.21 (s, 2H), 4.77 (s, 2H), 2.32 (s, 3H).

EXAMPLE 3(5)

[0528] 1-(4-(3-Methylbutoxy)benzoyl)-2-methylindolyl-4-oxyacetic Acid

298

[0529] TLC: Rf 0.46 (chloroform:methanol=5:1);

[0530] NMR (CDCl3): δ 7.64 (d, J=8.6 Hz, 2H), 6.92-6.84 (m, 3H), 6.70-6.45 (m, 3H), 4.72 (s, 2H), 4.05 (t, J=6.6 Hz, 2H), 2.37 (s, 3H), 1.83 (m, 1H), 1.72 (m, 2H), 0.97 (d, J=6.4 Hz, 6H).

EXAMPLE 3(6)

[0531] 1-(4-Pentoxybenzoyl)-2-methylindolyl-4-oxyacetic Acid

299

[0532] TLC: Rf 0.26 (chloroform:methanol=9:1);

[0533] NMR (CDCl3): δ 7.70 (d, J=8.7 Hz, 2H), 6.98-6.90 (m, 3H), 6.72 (d, J=8.7 Hz, 1H), 6.58 (brs, 1H), 6.52 (d, J=8.1 Hz, 1H), 4.80 (s, 2H), 4.04 (t, J=6.6 Hz, 2H), 2.43 (s, 3H), 2.10-1.30 (m, 7H), 0.95 (t, J=6.9 Hz, 3H).

REFERENCE EXAMPLE 17

[0534] 3-(2-Methylindol-4-yl)acrylic Acid Methyl Ester

300

[0535] To a solution 2-methyl-4-trifluoromethylsulfoxyindole (3.2 g; prepared in Reference Example 2) in N,N-dimethylformamide (50 ml) was added acrylic acid methyl ester (2.24 ml), diisopropylethylamine (5.9 ml) and dichlorobis(triphenylphosphine)palladium(II) (238 mg), and the mixture was stirred at 95° C. for 2 days. To the reaction mixture was added water and ethyl acetate, then separated. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with water and a saturated aqueous solution of sodium chloride, successively, dried and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (hexane—ethyl acetate) to give the title compound (950 mg) having the following physical data.

[0536] TLC: Rf 0.50 (hexane:ethyl acetate=8:2).

REFERENCE EXAMPLE 18

[0537] 3-(2-Methylindol-4-yl)acrylic Acid

301

[0538] A title compound (700 mg) having the following physical data was obtained by the same procedure as Reference Example 14, using 3-(2-methylindol-4-yl)acrylic acid methyl ester (950 mg; prepared in Reference Example 17).

[0539] TLC: Rf 0.54(chloroform:methanol=9:1).

REFERENCE EXAMPLE 19

[0540] 3-(2-Methylindol-4-yl)acrylic Acid Allyl Ester

302

[0541] A title compound (240 mg) having the following physical data was obtained by the same procedure as Reference Example 15, using 3-(2-methylindol-4-yl)acrylic acid (300 mg; prepared in Reference Example 18).

[0542] TLC: Rf 0.43 (hexane:ethyl acetate=8:2).

REFERENCE EXAMPLE 20

[0543] 3-(1-(4-Butoxybenzoyl)-2-methylindol-4-yl)acrylic Acid Allyl Ester

303

[0544] A title compound (545 mg) having the following physical data was obtained by the same procedure as Reference Example 16, using 3-(2-methylindol-4-yl)acrylic acid allyl ester (240 mg; prepared in Reference Example 19).

[0545] TLC: Rf 0.59 (hexane:ethyl acetate=8:2);

[0546] NMR (CDCl3): δ 8.10-8.00 (m, 1H), 7.70 (d, 2H), 7.39 (d, 1H), 7.10-6.90 (m, 4H), 6.72 (s, 1H), 6.58 (d, 1H), 6.10-5.95 (m, 1H), 5.95-5.85 (m, 1H9, 5.82-5.75 (m, 1H), 4.80-4.70 (m, 2H), 4.10-4.00 (m, 2H), 2.47 (s, 3H), 1.90-1.70 (m, 2H), 1.70-1.40 (m, 2H), 1.10-0.95 (m, 3H).

EXAMPLE 4

[0547] 3-(1-(4-Butoxybenzoyl)-2-methylindol-4-yl)acrylic Acid

304

[0548] A title compound (374 mg) having the following physical data was obtained by the same procedure as Example 1, using 3-(1-(4-butoxybenzoyl)-2-methylindol-4-yl)acrylic acid allyl ester (413 mg; prepared in Reference Example 20).

[0549] TLC: Rf 0.53 (chloroform:methanol=9:1);

[0550] NMR (CDCl3): δ 8.16 (d, J=16.2 Hz, 1H), 7.70 (d, J=9.0 Hz, 2H), 7.43 (brd, J=7.2 Hz, 1H), 7.15-7.03 (m, 2H), 6.96 (d, J=9.0 Hz, 2H), 6.74 (brs, 1H), 6.59 (d, J=16.2 Hz, 1H), 4.06 (t, J=6.3 Hz, 2H), 2.48 (s, 3H), 1.88-1.76 (m, 2H), 1.60-1.46 (m, 2H), 1.00 (t, J=7.2 Hz, 3H).

EXAMPLES 4(1) TO 4(7)

[0551] Each compound having the following physical data was obtained by the same procedures as a series of reactions of Reference Example 17, 18, 19, 20 and Example 4.

Example 4(1)

[0552] 3-(1-(4-Benzyloxybenzoyl)-2-methylindol-4-yl)-2-acrylic Acid

305

[0553] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0554] NMR (DMSO-d6): δ 7.90 (d, J=16 Hz, 1H), 7.65 (d, J=8.6 Hz, 2H), 7.60-7.30 (m, 6H), 7.17 (d, J=8.6 Hz, 2H), 7.16-7.05 (m, 2H), 6.90 (s, 1H), 6.60 (d, J=16 Hz, 1H), 5.21 (s, 2H), 2.36 (s, 3H).

Example 4(2)

[0555] 3-(1-(4-Pentyloxybenzoyl)-2-methylindol-4-yl)-2-acrylic Acid

306

[0556] TLC: Rf 0.31 (chloroform:methanol=9:1);

[0557] NMR (CDCl3): δ 8.15 (d, J=15.9 Hz, 1H), 7.70 (d, J=9.0 Hz, 2H), 7.43 (d, J=7.2 Hz, 1H), 7.15-7.02 (m, 2H), 6.96 (d, J=9.0 Hz, 2H), 6.74 (s, 1H), 6.58 (d, J=15.9 Hz, 1H), 4.05 (t, J=6.3 Hz, 2H), 2.48 (s, 3H), 2.00-1.30 (m, 7H), 0.95 (t, J=7.2 Hz, 3H).

Example 4(3)

[0558] 3-(1-(4-Phenethyloxybenzoyl)-2-methylindol-4-yl)-2-acrylic Acid

307

[0559] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0560] NMR (CDCl3): δ 8.16 (d, J=16 Hz, 1H), 7.68 (d, J=9.0 Hz, 2H), 7.44-7.26 (m, 6H), 7.09 (m, 2H), 6.96 (d, J=9.0 Hz, 2H), 6.74 (s, 1H), 6.58 (d, J=16 Hz, 1H), 4.27 (t, J=7.0 Hz, 2H), 3.15 (t, J=7.0 Hz, 2H), 2.47 (s, 3H).

Example 4(4)

[0561] 3-(1-(4-(3-Methylbutoxy)benzoyl)-2-methylindol-4-yl)-2-acrylic Acid

308

[0562] TLC: Rf 0.60 (chloroform:methanol=10:1);

[0563] NMR (DMSO-d6): δ 12.4 (brs, 1H), 7.90 (d, J=16 Hz, 1H), 7.66-7.60 (m, 2H), 7.52 (brd, J=6.4 Hz, 2H), 7.11-7.05 (m, 4H), 6.90 (s, 1H), 6.59 (d, J=16 Hz, 1H), 4.09 (t, J=6.4 Hz, 2H), 2.36 (s, 3H), 1.90-1.50 (m, 3H), 0.92 (dd, J=6.4, 2.0 Hz, 6H).

Example 4(5)

[0564] 3-(1-(4-(2-Ethoxyethoxy)benzoyl)-2-methylindol-4-yl)-2-acrylic Acid

309

[0565] TLC: Rf 0.60 (ethyl acetate);

[0566] NMR (CDCl3): δ 8.15 (d, J=15.9 Hz, 1H), 7.70 (d, J=9.0 Hz, 2H), 7.42 (m, 1H), 7.09-6.98 (m, 4H), 6.74 (s, 1H), 6.58 (d, J=15.9 Hz, 1H), 4.22 (t, J=4.6 Hz, 2H), 3.84 (t, J=4.6 Hz, 2H), 3.63 (q, J=7.0 Hz, 2H), 2.48 (d, J=1.0 Hz, 3H), 1.27 (t, J=7.0 Hz, 3H).

Example 4(6)

[0567] 3-(1-(4-Propyloxybenzoyl)-2-methylindol-4-yl)-2-acrylic Acid

310

[0568] TLC: Rf 0.48 (chloroform:methanol=9:1);

[0569] NMR (CDCl3): δ 8.15 (d, J=15.9 Hz, 1H), 7.71 (d, J=8.7 Hz, 2H), 7.43 (brd, J=7.2 Hz, 1H), 7.15-7.03 (m, 2H), 6.97 (d, J=8.7 Hz, 2H), 6.74 (s, 1H), 6.58 (d, J=15.9 Hz, 1H), 4.02 (t, J=6.6 Hz, 2H), 2.48 (s, 3H), 1.95-1.80 (m, 2H), 1.07 (t, J=7.5 Hz, 3H).

Example 4(7)

[0570] 3-(1-(4-(2-(Pyridin-2-yl)ethoxy)benzoyl)-2-methylindol-4-yl)-2-acrylic Acid

311

[0571] TLC: Rf 0.40 (chloroform:methanol=9:1);

[0572] NMR (CDCl3): δ 8.61 (d, J=5.0 Hz, 1H), 8.13 (d, J=16.0 Hz, 1H), 7.71-6.95 (m, 10H), 6.72 (s, 1H), 6.58 (d, J=16.0 Hz, 1H), 4.19 (t, J=6.8 Hz, 2H), 3.34 (t, J=6.8 Hz, 2H), 2.45 (s, 3H).

EXAMPLE 5

[0573] 3-(1-(4-Butoxybenzoyl)-2-methylindol-4-yl)propionic Acid

312

[0574] To a solution of 3-(1-(4-butoxybenzoyl)-2-methylindol-4-yl)acrylic acid (300 mg; prepared in Example 4) in methanol—ethyl acetate (5 ml+5 ml) was added palladium on activated carbon (100 mg) at room temperature. The inside of the vessel was replaced with hydrogen and the mixture was stirred at room temperature for 2 hours. The mixture was filtered through Celite (trademark). The filtrate and washing with chloroform were combined, and then concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (chloroform—methanol) to give the title compound (25 mg) having the following physical data.

[0575] TLC: Rf 0.58 (chloroform:methanol=9:1);

[0576] NMR (CDCl3): δ 7.70 (d, J=9.3 Hz, 2H), 7.00-6.86 (m, 5H), 6.48 (s, 1H), 4.05 (t, J=6.6 Hz, 2H), 3.75-3.65 (br, 1H), 3.19 (t, J=8.4 Hz, 2H), 2.79 (t, J=8.4 Hz, 2H), 2.45 (s, 3H), 1.87-1.72 (m, 2H), 1.60-1.40 (m, 2H), 1.00 (t, J=7.5 Hz, 3H).

REFERENCE EXAMPLE 21

[0577] 4-(1-(4-Butoxybenzoyl)-2-methylindol-4-yl)butanoic Acid Benzyl Ester

313

[0578] (1) To a solution of 3-(1-(4-butoxybenzoyl)-2-methylindol-4-yl)propionic acid (1.77 g; prepared in Example 5) in toluene (20 ml) was added oxalyl chloride (0.64 ml) and N,N-dimethylformamide (few drops) at room temperature, and the mixture was stirred at room temperature for 1 hour.

[0579] To a solution of the acid chloride prepared in (1) in tetrahydrofuran—acetonitrile (4 ml+4 ml) was added trimethylsilyidiazomethane (4.67 ml; 2M) at 0° C. The mixture was stirred at the same temperature for 1 hour and then concentrated under reduced pressure. To the residue was added benzyl alcohol (4 ml) and 2,4,6-collidine (4 ml), and the mixture was stirred at 180° C. for 30 minutes. After cooling to room temperature, the reaction mixture was purified by column chromatography on silica gel (hexane—ethyl acetate) to give the title compound (460 mg) having the following physical data.

[0580] TLC: Rf 0.51 (hexane:ethyl acetate=8:2).

EXAMPLE 6

[0581] 4-(1-(4-Butoxybenzoyl)-2-methylindol-4-yl)butanoic Acid

314

[0582] A title compound (170 mg) having the following physical data was obtained by the same procedure as Example 2, using 4-(1-(4-butoxybenzoyl)-2-methylindol-4-yl)butanoic acid benzyl ester (460 mg; prepared in Reference Example 21).

[0583] TLC: Rf 0.50 (chloroform:methanol=9:1);

[0584] NMR (CDCl3): δ 7.71 (d, J=9.0 Hz, 2H), 7.00-6.86 (m, 5H), 6.48 (s, 1H), 4.05 (t, J=6.6 Hz, 2H), 2.90 (t, J=7.2 Hz, 2H), 2.48-2.38 (m, 5H), 2.14-2.00 (m, 2H), 2.00-1.40 (m, 5H), 1.00 (t, J=7.5 Hz, 3H).

EXAMPLES 7 TO EXAMPLE 7(228)

[0585] The compounds of the present invention having the following physical data were obtained by the same procedures as a series of reactions of Reference Example 7→Reference Example 8→Example 1. In Examples 7(37) and 7(151), hydroxy or amino group was protected by protective group, and the protective group was removed before the reaction corresponding Example 1.

EXAMPLE 7

[0586] 1-(4-Butoxybenzoyl)-5-methoxy-2-methylindole-4-acetic Acid

315

[0587] TLC: Rf 0.48 (chloroform:methanol=10:1);

[0588] MS: (MALDI, Pos.): 434 (M+K)+, 418 (M+Na)+, 396 (M+H)+;

[0589] NMR (CDCl3): δ 7.70-7.67 (m, 2H), 6.98-6.93 (m, 3H), 6.70 (d, J=9.3 Hz, 1H), 6.41 (s, 1H), 4.05 (t, J=6.5 Hz, 2H), 3.90 (s, 2H), 3.86 (s, 3H), 2.41 (s, 3H), 1.82 (m, 2H), 1.54 (m, 2H), 1.00 (t, J=7.5 Hz, 3H).

Example 7(1)

[0590] 1-(4-(2-Methylbutyloxy)benzoyl)-2-methylindole-4-acetic Acid

316

[0591] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0592] MS: (MALDI, Pos.): 418 (M+K)+, 402 (M+Na)+.

Example 7(2)

[0593] 1-(4-Cyclopentyloxybenzoyl)-2-methylindole-4-acetic Acid

317

[0594] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0595] MS: (APCI, Neg.): 376 (M−H)−.

Example 7(3)

[0596] 1-(4-(1-Ethylpropyloxy)benzoyl)-2-methylindole-4-acetic Acid

318

[0597] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0598] MS: (APCI, Neg.): 378 (M−H)−.

Example 7(4)

[0599] 1-(4-(Tetrahydrofuran-3-yloxy)benzoyl)-2-methylindole-4-acetic Acid

319

[0600] TLC: Rf 0.50 (chloroform:methanol=10:1);

[0601] MS: (APCI, Neg.): 378 (M−H)−.

Example 7(5)

[0602] 1-(4-(1,2-Dimethylpropyloxy)benzoyl)-2-methylindole-4-acetic Acid

320

[0603] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0604] MS: (MALDI, Pos.): 418 (M+K)+, 402 (M+Na)+.

Example 7(6)

[0605] 1-(4-Cyclobutyloxybenzoyl)-2-methylindole-4-acetic Acid

321

[0606] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0607] MS: (MALDI, Pos.): 402 (M+K)+, 386 (M+Na)+.

Example 7(7)

[0608] 1-(4-(1-Methylcyclopropylmethyl)benzoyl)-2-methylindole-4-acetic Acid

322

[0609] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0610] MS: (MALDI, Pos.): 416 (M+K)+, 400 (M+Na)+.

Example 7(8)

[0611] 1-(4-Cyclobutylmethyloxybenzoyl)-2-methylindole-4-acetic Acid

323

[0612] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0613] MS: (MALDI, Pos.): 416 (M+K)+, 400 (M+Na)+.

Example 7(9)

[0614] 1-(4-(2-Benzyloxyethyloxy)benzoyl)-2-methylindole-4-acetic Acid

324

[0615] TLC: Rf 0.53 (chloroform:methanol=10:1);

[0616] MS: (APCI, Neg.): 442 (M−H)−.

Example 7(10)

[0617] 1-(4-Cyclopropylmethyloxybenzoyl)-2-methylindole-4-acetic Acid

325

[0618] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0619] MS: (MALDI, Pos.):402 (M+K)+, 386 (M+Na)+.

Example 7(11)

[0620] 1-(4-(3,7-Dimethyl-6-octen-1-yloxy)benzoyl)-2-methylindole-4-acetic Acid

326

[0621] TLC: Rf 0.53 (chloroform:methanol=10:1);

[0622] MS: (MALDI, Pos.): 486 (M+K)+, 470 (M+Na)+.

Example 7(12)

[0623] 1-(4-(3-(3,4-Dimethoxyphenyl)propyloxy)benzoyl)-2-methylindole-4-acetic Acid

327

[0624] TLC: Rf 0.52 (chloroform:methanol=10:1);

[0625] MS: (MALDI, Pos.): 526 (M+K)+, 510 (M+Na)+.

Example 7(13)

[0626] 1-(4-(4-(4-Methoxyphenyl)butyloxy)benzoyl)-2-methylindole-4-acetic Acid

328

[0627] TLC: Rf 0.52 (chloroform:methanol=10:1);

[0628] MS: (MALDI, Pos.): 510 (M+K)+, 494 (M+Na)+.

Example 7(14)

[0629] 1-(4-(2,3,5,6-Tetrahydropyran-4-yloxy)benzoyl)-2-methylindole-4-acetic Acid

329

[0630] TLC: Rf 0.33 (chloroform:methanol=10:1);

[0631] MS: (MALDI, Pos.): 432 (M+K)+, 416 (M+Na)+, 393 (M)+.

Example 7(15)

[0632] 1-(4-(1-Methylpropyloxy)benzoyl)-2-methylindole-4-acetic Acid

330

[0633] TLC: Rf 0.33 (chloroform:methanol=10:1);

[0634] MS: (MALDI, Pos.): 365 (M)+.

Example 7(16)

[0635] 1-(4-(5-Chloropentyloxy)benzoyl)-2-methylindole-4-acetic Acid

331

[0636] TLC: Rf 0.28 (chloroform:methanol=10:1);

[0637] MS: (MALDI, Pos.): 436 (M+Na)+, 413 (M)+.

Example 7(17)

[0638] 1-(4-(2,3,4,5-Tetrahydrofuran-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

332

[0639] TLC: Rf 0.27 (chloroform:methanol=10:1);

[0640] MS: (MALDI, Pos.): 432 (M+K)+, 416 (M+Na)+, 394 (M+H)+, 393 (M)+.

Example 7(18)

[0641] 1-(4-(2-(N,N-Diethylamino)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

333

[0642] TLC: Rf 0.08 (chloroform:methanol=2:1);

[0643] MS: (MALDI, Pos.): 409 (M+H)+.

Example 7(19)

[0644] 1-(4-(2-(Piperid in-1-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

334

[0645] TLC: Rf 0.16 (chloroform:methanol=2:1);

[0646] MS: (MALDI, Pos.): 443 (M+Na)+, 421 (M+H)+.

Example 7(20)

[0647] 1-(4-(2-Cyclopentylethyloxy)benzoyl)-2-methylindole-4-acetic Acid

335

[0648] TLC: Rf 0.33 (chloroform:methanol=10:1);

[0649] MS: (MALDI, Pos.):428 (M+Na)+, 406 (M+H)+.

Example 7(21)

[0650] 1-(4-(3-Methoxy-3-methylbutyloxy)benzoyl)-2-methylindole-4-acetic Acid

336

[0651] TLC: Rf 0.34 (chloroform:methanol=10:1);

[0652] MS: (MALDI, Pos.): 448 (M+Na)+, 432 (M+H)+.

Example 7(22)

[0653] 1-(4-(2-(3,5-Dimethylpyrazol-1-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

337

[0654] TLC: Rf 0.33 (chloroform:methanol=10:1);

[0655] MS: (APCI, Neg.): 430 (M−H)−.

Example 7(23)

[0656] 1-(4-(2-(N,N-Diallylamino)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

338

[0657] TLC: Rf 0.31 (chloroform:methanol=10:1);

[0658] MS: (APCI, Neg.): 431 (M−H)−.

Example 7(24)

[0659] 1-(4-(6-(N,N-Dimethylamino)hexyloxy)benzoyl)-2-methylindole-4-acetic Acid

339

[0660] TLC: Rf 0.53 (chloroform:methanol=10:1);

[0661] MS: (APCI, Neg.): 435 (M−H)−.

Example 7(25)

[0662] 1-(4-(3-Butyn-1-yloxy)benzoyl)-2-methylindole-4-acetic Acid

340

[0663] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0664] MS: (APCI, Neg.): 360 (M−H)−.

Example 7(26)

[0665] 1-(4-Cyclohexylmethyloxybenzoyl)-2-methylindole-4-acetic Acid

341

[0666] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0667] MS: (MALDI, Pos.): 444 (M+K)+, 428 (M+Na)+.

Example 7(27)

[0668] 1-(4-(2-(Pyrrol-1-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

342

[0669] TLC:Rf 0.53 (chloroform:methanol=10:1);

[0670] MS: (MALDI, Pos.): 441 (M+K)+, 425 (M+Na)+.

Example 7(28)

[0671] 1-(4-(2-(3,4-Dimethoxyphenyl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

343

[0672] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0673] MS: (MALDI, Pos.): 512 (M+K)+, 496 (M+Na)+.

Example 7(29)

[0674] 1-(4-(3-Pentyn-1-yloxy)benzoyl)-2-methylindole-4-acetic Acid

344

[0675] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0676] MS: (MALDI, Pos.): 414 (M+K)+, 398 (M+Na)+.

Example 7(30)

[0677] 1-(4-Phenylbuthyloxybenzoyl)-2-methylindole-4-acetic Acid

345

[0678] TLC: Rf 0.55 (chloroform:methanol=10:1);

[0679] MS: (MALDI, Pos.): 480 (M+K)+, 464 (M+Na)+.

Example 7(31)

[0680] 1-(4-(4-Methylthiobutyloxy)benzoyl)-2-methylindole-4-acetic Acid

346

[0681] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0682] MS: (MALDI, Pos.): 450 (M+K)+, 434 (M+Na)+.

Example 7(32)

[0683] 1-(4-(4-Pentyn-1-yloxy)benzoyl)-2-methylindole-4-acetic Acid

347

[0684] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0685] MS: (MALDI, Pos.): 414 (M+K)+, 398 (M+Na)+.

Example 7(33)

[0686] 1-(4-(2-Phenylthioethyloxy)benzoyl)-2-methylindole-4-acetic Acid

348

[0687] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0688] MS: (MALDI, Pos.): 484 (M+K)+, 468 (M+Na)+.

Example 7(34)

[0689] 1-(4-(4-Penten-1-yloxy)benzoyl)-2-methylindole-4-acetic Acid

349

[0690] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0691] MS: (MALDI, Pos.):416 (M+K)+, 400 (M+Na)+.

Example 7(35)

[0692] 1-(4-(5-Hexen-1-yloxy)benzoyl)-2-methylindole-4-acetic Acid

350

[0693] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0694] MS: (MALDI, Pos.): 430 (M+K)+, 414 (M+Na)+.

Example 7(36)

[0695] 1-(4-(2-Benzylthioethyloxy)benzoyl)-2-methylindole-4-acetic Acid

351

[0696] TLC: Rf 0.53 (chloroform:methanol=10:1);

[0697] MS: (MALDI, Pos.): 498 (M+K)+, 482 (M+Na)+.

Example 7(37)

[0698] 1-(4-(6-Hydroxyhexyloxy)benzoyl)-2-methylindole-4-acetic Acid

352

[0699] TLC: Rf 0.47 (chloroform:methanol=10:1);

[0700] MS: (MALDI, Pos.): 508 (M+K)+, 492 (M+Na)+.

Example 7(38)

[0701] 1-(4-(2-(4-Ethoxyphenyl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

353

[0702] TLC: Rf 0.53 (chloroform:methanol=10:1);

[0703] MS: (MALDI, Pos.): 496 (M+K)+, 480 (M+Na)+.

Example 7(39)

[0704] 1-(4-(2-Butoxyethyloxy)benzoyl)-2-methylindole-4-acetic Acid

354

[0705] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0706] MS: (APCI, Neg.): 408 (M−H)−.

Example 7(40)

[0707] 1-(4-(3-Methyloxetan-3-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

355

[0708] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0709] MS: (APCI, Neg.): 392 (M−H)−.

Example 7(41)

[0710] 1-(4-(2-(N-Ethyl-N-(3-methylphenyl)amino)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

356

[0711] TLC: Rf 0.55 (chloroform:methanol=10:1);

[0712] MS: (MALDI, Pos.): 471 (M+H)+.

Example 7(42)

[0713] 1-(4-(2-(N-Methyl-N-phenylamino)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

357

[0714] TLC: Rf 0.55 (chloroform:methanol=10:1);

[0715] MS: (MALDI, Pos.): 481 (M+K)+, 465 (M+Na)+, 443 (M+H)+.

Example 7(43)

[0716] 1-(4-(3-(4-Methoxyphenyl)propyloxy)benzoyl)-2-methylindole-4-acetic Acid

358

[0717] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0718] MS: (MALDI, Pos.): 496 (M+K)+, 480 (M+Na)+.

Example 7(44)

[0719] 1-(4-(3-Nonyn-1-yloxy)benzoyl)-2-methylindole-4-acetic Acid

359

[0720] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0721] MS: (MALDI, Pos.): 470 (M+K)+, 454 (M+Na)+.

Example 7(45)

[0722] 1-(4-(2-(4-Chlorophenylthio)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

360

[0723] TLC: Rf 0.53 (chloroform:methanol=10:1);

[0724] MS: (MALDI, Pos.):518 (M+K)+, 502 (M+Na)+.

Example 7(46)

[0725] 1-(4-(2-Phenylaminoethyloxy)benzoyl)-2-methylindole-4-acetic Acid

361

[0726] TLC: Rf 0.55 (chloroform:methanol=10:1);

[0727] MS: (APCI, Neg.): 427 (M−H)−.

Example 7(47)

[0728] 1-(4-(3-(Pyrid in-3-yl)propyloxy)benzoyl)-2-methylindole-4-acetic Acid

362

[0729] TLC: Rf 0.57 (chloroform:methanol=10:1);

[0730] MS: (MALDI, Pos.): 467 (M+K)+, 451 (M+Na)+.

Example 7(48)

[0731] 1-(4-(2-(3-Trifluoromethylphenyl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

363

[0732] TLC: Rf 0.60 (chloroform:methanol 10:1);

[0733] MS: (MALDI, Pos.): 520 (M+K)+, 504 (M+Na)+.

Example 7(49)

[0734] 1-(4-(2-(2-Chlorophenyloxy)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

364

[0735] TLC: Rf 0.61 (chloroform:methanol=10:1);

[0736] MS: (MALDI, Pos.): 504 (M+K)+, 488 (M+Na)+.

Example 7(50)

[0737] 1-(4-(2-(3-Methylphenyloxy)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

365

[0738] TLC: Rf 0.65 (chloroform:methanol=10:1);

[0739] MS: (MALDI, Pos.): 482 (M+K)+, 466 (M+Na)+.

Example 7(51)

[0740] 1-(4-Butoxybenzoyl)-6-methoxy-2-methylindole-4-acetic Acid

366

[0741] TLC: Rf 0.44 (chloroform:methanol=10:1);

[0742] MS: (MALDI, Pos.): 434 (M+K)+, 418 (M+Na)+, 395 (M)+;

[0743] NMR (CDCl3): δ 7.70 (m, 2H), 6.95 (m, 2H), 6.73 (d, J=2.1 Hz, 1H), 6.68 (d, J=2.1 Hz, 1H), 6.38 (s, 1H), 4.04 (t, J=6.6 Hz, 2H), 3.81 (s, 2H), 3.65 (s, 3H), 2.34 (s, 3H), 1.81 (m, 2H), 1.51 (m, 2H), 0.99 (t, J=7.5 Hz, 3H).

Example 7(52)

[0744] 1-(4-(Thiophen-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

367

[0745] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0746] MS: (APCI, Neg.): 404 (M−H)−.

Example 7(53)

[0747] 1-(4-(2-(2-Chloroethyloxy)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

368

[0748] TLC: Rf 0.53 (chloroform:methanol=10:1);

[0749] MS: (APCI, Neg.): 414 (M−H)−.

Example 7(54)

[0750] 1-(4-(2-(Morpholin-4-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

369

[0751] TLC: Rf 0.33 (chloroform methanol=10:1);

[0752] MS: (APCI, Neg.): 421 (M−H)−.

Example 7(55)

[0753] 1-(4-(5-Hexyn-1-yloxy)benzoyl)-2-methylindole-4-acetic Acid

370

[0754] TLC: Rf 0.52 (chloroform:methanol=10:1);

[0755] MS: (APCI, Neg.): 388 (M−H)−.

Example 7(56)

[0756] 1-(4-(4-Methyl-3-penten-1-yloxy)benzoyl)-2-methylindole-4-acetic Acid

371

[0757] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0758] MS: (APCI, Neg.): 390 (M−H)−.

Example 7(57)

[0759] 1-(4-(2-(5-Methylfuran-2-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

372

[0760] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0761] MS: (APCI, Neg.): 416 (M−H)−.

Example 7(58)

[0762] 1-(4-(2-(Furan-2-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

373

[0763] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0764] MS: (APCI, Neg.): 402 (M−H)−.

Example 7(59)

[0765] 1-(4-(2-Cyclobutyloxyethyloxy)benzoyl)-2-methylindole-4-acetic Acid

374

[0766] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0767] MS: (APCI, Neg.): 406 (M−H)−.

Example 7(60)

[0768] 1-(4-(2-(2,4-Difluorophenyl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

375

[0769] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0770] MS: (APCI, Neg.): 448 (M−H)−.

Example 7(61)

[0771] 1-(4-(2-(2,5-Difluorophenyl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

376

[0772] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0773] MS: (APCI, Neg.): 448 (M−H)−.

Example 7(62)

[0774] 1-(4-(2-(2-Ethoxyphenyl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

377

[0775] TLC: Rf 0.53 (chloroform:methanol=10:1);

[0776] MS: (APCI, Neg.): 456 (M−H)−.

Example 7(63)

[0777] 1-(4-(2-(2-Methylpropyloxy)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

378

[0778] TLC: Rf 0.51 (chloroform methanol=10:1);

[0779] MS: (APCI, Neg.): 408 (M−H)−.

Example 7(64)

[0780] 1-(4-(4-Methoxybutyloxy)benzoyl)-2-methylindole-4-acetic Acid

379

[0781] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0782] MS: (APCI, Neg.): 394 (M−H)−.

Example 7(65)

[0783] 1-(4-(2-(2,5-Dimethylphenyl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

380

[0784] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0785] MS: (APCI, Neg.): 440 (M−H)−.

Example 7(66)

[0786] 1-(4-(2-(2-(2-Methoxyethyloxy)ethyloxy)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

381

[0787] TLC: Rf 0.55 (chloroform:methanol=10:1);

[0788] MS: (APCI, Neg.): 454 (M−H)−.

Example 7(67)

[0789] 1-(4-(2-(2,4-Dimethoxyphenyl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

382

[0790] TLC: Rf 0.52 (chloroform:methanol=10:1);

[0791] MS: (APCI, Neg.): 472 (M−H)−.

Example 7(68)

[0792] 1-(4-(2-(2,3-Difluorophenyl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

383

[0793] TLC: Rf 0.53 (chloroform:methanol=10:1);

[0794] MS: (APCI, Neg.): 448 (M−H)−.

Example 7(69)

[0795] 1-(4-(1-Phenylcyclopropylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

384

[0796] TLC: Rf 0.53 (chloroform:methanol=10:1);

[0797] MS: (APCI, Neg.): 438 (M−H)−.

Example 7(70)

[0798] 1-(4-(2-(3-Methoxymethylphenyl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

385

[0799] TLC: Rf 0.53 (chloroform:methanol=10:1);

[0800] MS: (APCI, Neg.): 456 (M−H)−.

Example 7(71)

[0801] 1-(4-(F uran-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

386

[0802] TLC: Rf 0.51 (chloroform:methanol=10:1);

[0803] MS: (APCI, Neg.): 388 (M−H)−.

Example 7(72)

[0804] 1-(4-(2-(N-Benzyl-N-methylamino)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

387

[0805] TLC: Rf 0.35 (chloroform:methanol=10:1);

[0806] MS: (APCI, Neg.): 455 (M−H)−.

Example 7(73)

[0807] 1-(4-(2-(2-Butoxyethyloxy)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

388

[0808] TLC: Rf 0.55 (chloroform:methanol=10:1);

[0809] MS: (APCI, Neg.): 452 (M−H)−.

Example 7(74)

[0810] 1-(4-(2-Methoxy-3-phenoxypropyloxy)benzoyl)-2-methylindole-4-acetic Acid

389

[0811] TLC: Rf 0.53 (chloroform:methanol=10:1);

[0812] MS: (APCI, Neg.): 472 (M−H)−.

Example 7(75)

[0813] 1-(4-(2-(4-Methylphenyloxy)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

390

[0814] TLC: Rf 0.44 (chloroform:methanol=10:1);

[0815] MS: (APCI, Neg.): 442 (M−H)−.

Example 7(76)

[0816] 1-(4-(2-(2-(2-Ethoxyethyloxy)ethyloxy)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

391

[0817] TLC: Rf 0.36 (chloroform:methanol=10:1);

[0818] MS: (APCI, Neg.): 468 (M−H)−.

Example 7(77)

[0819] 1-(4-(2-(Naphthalen-1-ylamino)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

392

[0820] TLC: Rf 0.33 (chloroform:methanol=10:1);

[0821] MS: (APCI, Neg.): 477 (M−H)−.

Example 7(78)

[0822] 1-(4-(2-(Naphthalen-1-yloxy)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

393

[0823] TLC: Rf 0.37 (chloroform:methanol=10:1);

[0824] MS: (APCI, Neg.): 478 (M−H)−.

Example 7(79)

[0825] 1-(4-(2-(Pyrazol-1-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

394

[0826] TLC: Rf 0.32 (chloroform:methanol=10:1);

[0827] MS: (APCI, Neg.): 402 (M−H)−.

Example 7(80)

[0828] 1-(4-(2-(2-Propen-1-yloxy)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

395

[0829] TLC: Rf 0.33 (chloroform:methanol=10:1);

[0830] MS: (APCI, Neg.): 392 (M−H)−.

Example 7(81)

[0831] 1-(4-(4,4,4-Trifluorobutyloxy)benzoyl)-2-methylindole-4-acetic Acid

396

[0832] TLC: Rf 0.40 (chloroform:methanol=10:1);

[0833] MS: (APCI, Neg.): 418 (M−H)−.

Example 7(82)

[0834] 1-(4-(Indan-2-yloxy)benzoyl)-2-methylindole-4-acetic Acid

397

[0835] TLC: Rf 0.36 (chloroform:methanol=10:1);

[0836] MS: (APCI, Neg.): 424 (M−H)−.

Example 7(83)

[0837] 1-(4-(2-(2-Methylphenyloxy)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

398

[0838] TLC: Rf 0.38 (chloroform:methanol=10:1);

[0839] MS: (APCI, Neg.): 442 (M−H)−.

Example 7(84)

[0840] 1-(4-(1,4-Benzodioxan-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

399

[0841] TLC: Rf 0.34 (chloroform:methanol=10:1);

[0842] MS: (FAB, Pos.): 458 (M+H)+;

[0843] NMR (CDCl3): δ 7.71 (d, J=8.8 Hz, 2H), 7.09-6.82 (m, 9H), 6.48 (s, 1H), 4.61 (m, 2H), 4.42 (dd, J=11.8, 2.6 Hz, 1H), 4.38-4.18 (m, 3H), 3.84 (s, 2), 2.43 (s, 3H).

Example 7(85)

[0844] 1-(4-(2-(2-Chlorophenyl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

400

[0845] TLC: Rf 0.39 (chloroform:methanol=10:1);

[0846] MS: (APCI, Neg.): 446 (M−H)−.

Example 7(86)

[0847] 1-(4-(2-(2-Ethoxyethyloxy)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

401

[0848] TLC: Rf 0.37 (chloroform:methanol=10:1);

[0849] MS: (APCI, Neg.): 424 (M−H)−.

Example 7(87)

[0850] 1-(4-(5-Ethoxypentyloxy)benzoyl)-2-methylindole-4-acetic Acid

402

[0851] TLC: Rf 0.35 (chloroform:methanol=10:1);

[0852] MS: (APCI, Neg.): 422 (M−H)−.

Example 7(88)

[0853] 1-(4-(5-Methoxypentyloxy)benzoyl)-2-methylindole-4-acetic Acid

403

[0854] TLC: Rf 0.33 (chloroform:methanol=10:1);

[0855] MS: (APCI, Neg.): 408 (M−H)−.

Example 7(89)

[0856] 1-(4-((3E)-4-Phenyl-3-buten-1-yloxy)benzoyl)-2-methylindole-4-acetic Acid

404

[0857] TLC: Rf 0.29 (chloroform:methanol=10:1);

[0858] MS: (APCI, Neg.): 438 (M−H)−.

Example 7(90)

[0859] 1-(4-(2-(N-Benzoyl-N-methylamino)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

405

[0860] TLC: Rf 0.30 (chloroform:methanol=10:1);

[0861] MS: (APCI, Neg.): 469 (M−H)−.

Example 7(91)

[0862] 1-(4-(4-Ethoxybutyloxy)benzoyl)-2-methylindole-4-acetic Acid

406

[0863] TLC: Rf 0.34 (chloroform methanol=10:1);

[0864] MS: (APCI, Neg.): 408 (M−H)−.

Example 7(92)

[0865] 1-(4-(3-(Pyrrol-1-yl)propyloxy)benzoyl)-2-methylindole-4-acetic Acid

407

[0866] TLC: Rf 0.43 (chloroform:methanol=10:1);

[0867] MS: (APCI, Neg.): 415 (M−H)−.

Example 7(93)

[0868] 1-(4-(2-(Naphthalen-2-yloxy)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

408

[0869] TLC: Rf 0.40 (chloroform methanol=10:1);

[0870] MS: (APCI, Neg.): 478 (M−H)−.

Example 7(94)

[0871] 1-(4-(2-(2,4,6-Trimethylphenyl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

409

[0872] TLC: Rf 0.40 (chloroform:methanol=10:1);

[0873] MS: (APCI, Neg.): 454 (M−H)−.

Example 7(95)

[0874] 1-(4-(3-Benzyloxypropyloxy)benzoyl)-2-methylindole-4-acetic Acid

410

[0875] TLC: Rf 0.41 (chloroform:methanol=10:1);

[0876] MS: (APCI, Neg.): 456 (M−H)−.

Example 7(96)

[0877] 1-(4-(3,3,4,4,5,5,6,6,6-Nonafluorohexyloxy)benzoyl)-2-methylindole-4-acetic Acid

411

[0878] TLC: Rf 0.42 (chloroform:methanol=10:1);

[0879] MS: (APCI, Neg.): 554 (M−H)−.

Example 7(97)

[0880] 1-(4-(3-Phenoxypropyloxy)benzoyl)-2-methylindole-4-acetic Acid

412

[0881] TLC: Rf 0.44 (chloroform:methanol=10:1);

[0882] MS: (APCI, Neg.): 442 (M−H)−.

Example 7(98)

[0883] 1-(4-(3-(2-Fluoroethyloxy)propyloxy)benzoyl)-2-methylindole-4-acetic Acid

413

[0884] TLC: Rf 0.35 (chloroform:methanol=10:1);

[0885] MS: (APCI, Neg.): 412 (M−H)−.

Example 7(99)

[0886] 1-(4-(2-Cyclopentyloxyethyloxy)benzoyl)-2-methylindole-4-acetic Acid

414

[0887] TLC: Rf 0.36 (chloroform:methanol=10:1);

[0888] MS: (APCI, Neg.): 420 (M−H)−.

Example 7(100)

[0889] 1-(4-(3-(2,2,2-Trifluoroethyloxy)propyloxy)benzoyl)-2-methylindole-4-acetic Acid

415

[0890] TLC: Rf 0.41 (chloroform:methanol=10:1);

[0891] MS: (APCI, Neg.): 448 (M−H)−.

Example 7(101)

[0892] 1-(4-(2-Cyclopropylmethyloxyethyloxy)benzoyl)-2-methylindole-4-acetic Acid

416

[0893] TLC: Rf 0.47 (chloroform:methanol=10:1);

[0894] MS: (APCI, Neg.): 406 (M−H)−.

Example 7(102)

[0895] 1-(4-(2-(3,3,3-Trifluoropropyloxy)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

417

[0896] TLC: Rf 0.39 (chloroform:methanol=10:1);

[0897] MS: (APCI, Neg.): 448 (M−H)−.

Example 7(103)

[0898] 1-(4-(2-(2,2,2-Trifluoroethyloxy)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

418

[0899] TLC: Rf 0.39 (chloroform:methanol=10:1);

[0900] MS: (APCI, Neg.): 434 (M−H)−.

Example 7(104)

[0901] 1-(4-(2-(2-Fluoroethyloxy)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

419

[0902] TLC: Rf 0.38 (chloroform:methanol=10:1);

[0903] MS: (APCI, Neg.): 398 (M−H)−.

Example 7(105)

[0904] 1-(4-(2-(2,4-Dichlorophenyl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

420

[0905] TLC: Rf 0.44 (chloroform:methanol=10:1);

[0906] MS: (APCI, Neg.): 480 (M−H)−.

Example 7(106)

[0907] 1-(4-(2-(2,3,4,5,6-Pentamethylphenyl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

421

[0908] TLC: Rf 0.50 (chloroform:methanol=10:1);

[0909] MS: (APCI, Neg.):482 (M−H)−.

Example 7(107)

[0910] 1-(4-(3,3,3-Trifluoropropyloxy)benzoyl)-2-methylindole-4-acetic Acid

422

[0911] TLC: Rf 0.32 (chloroform:methanol=10:1);

[0912] MS: (APCI, Neg.): 404 (M−H)−.

Example 7(108)

[0913] 1-(4-(2-(4-Methyl-1,3-thiazol-5-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

423

[0914] TLC: Rf 0.28 (chloroform:methanol=10:1);

[0915] MS: (APCI, Neg.): 433 (M−H)−.

Example 7(109)

[0916] 1-(4-(2-(Imidazol-1-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

424

[0917] TLC: Rf 0.45 (chloroform:methanol=2:1);

[0918] MS: (FAB, Pos.): 404 (M+H)+.

Example 7(110)

[0919] 1-(4-(2-(2-Methylimidazol-1-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

425

[0920] TLC: Rf 0.28 (chloroform:methanol=2:1);

[0921] MS: (APCI, Neg.): 416 (M−H)−.

Example 7(111)

[0922] 1-(4-(1,3-Dioxaindan-4-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

426

[0923] TLC: Rf 0.45 (chloroform:methanol=9:1);

[0924] MS: (APCI, Neg.): 442 (M−H)−.

Example 7(112)

[0925] 1-(4-(Naphthalen-1-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

427

[0926] TLC: Rf 0.43 (chloroform:methanol=9:1);

[0927] MS: (APCI, Neg.): 448 (M−H)−.

Example 7(113)

[0928] 1-(4-(3-(2-Pyrrolidinon-1-ylpropyloxy)benzoyl)-2-methylindole-4-acetic Acid

428

[0929] TLC: Rf 0.38 (chloroform:methanol=9:1);

[0930] MS: (APCI, Neg.20 V): 433 (M−H)−.

Example 7(114)

[0931] 1-(4-(Pyridin-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

429

[0932] TLC: Rf 0.42 (chloroform:methanol=9:1);

[0933] MS: (APCI, Neg.): 399 (M−H)−.

Example 7(115)

[0934] 1-(4-(1-Benzylethyloxy)benzoyl)-2-methylindole-4-acetic Acid

430

[0935] TLC: Rf 0.45 (chloroform:methanol=9:1);

[0936] MS: (APCI, Neg.): 426 (M−H)−.

Example 7(116)

[0937] 1-(4-((3Z)-3-Octen-1-yloxy)benzoyl)-2-methylindole-4-acetic Acid

431

[0938] TLC: Rf 0.50 (chloroform:methanol=9:1);

[0939] MS: (APCI, Neg.): 418 (M−H)−.

Example 7(117)

[0940] 1-(4-(2-Phenylpropyloxy)benzoyl)-2-methylindole-4-acetic Acid

432

[0941] TLC: Rf 0.48 (chloroform:methanol=9:1);

[0942] MS: (APCI, Neg.): 426 (M−H)−.

Example 7(118)

[0943] 1-(4-(Naphthalen-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

433

[0944] TLC: Rf 0.45 (chloroform:methanol=9:1);

[0945] MS: (APCI, Neg.: 448 (M−H)−.

Example 7(119)

[0946] 1-(4-(3-Chloropropyloxy)benzoyl)-2-methylindole-4-acetic Acid

434

[0947] TLC: Rf 0.43 (chloroform:methanol=9:1);

[0948] MS: (APCI, Neg.): 384 (M−H)−.

Example 7(120)

[0949] 1-(4-(2-(2,3-Dimethylphenyl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

435

[0950] TLC: Rf 0.47 (chloroform:methanol=9:1);

[0951] MS: (APCI, Neg.): 440 (M−H)−;

[0952] NMR (CDCl3): δ 7.70 (d, J=8.7 Hz, 2H), 7.12-6.90 (m, 8H), 6.49 (s, 1H), 4.21 (t, J=7.5 Hz, 2H), 3.87 (s, 2H), 3.19 (t, J=7.5 Hz, 2H), 2.45 (s, 3H), 2.31 (s, 3H), 2.30 (s, 3H).

Example 7(121)

[0953] 1-(4-(2-(4-Methoxymethylphenyl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

436

[0954] TLC: Rf 0.48 (chloroform:methanol=9:1);

[0955] MS: (APCI, Neg.): 456 (M−H)−;

[0956] NMR (CDCl3): δ 7.69 (d, J=9.0 Hz, 2H), 7.34-7.24 (m, 3H), 7.10-6.85 (m, 6H), 6.48 (s, 1H), 4.45 (s, 2H), 4.24 (t, J=6.9 Hz, 2H), 3.86 (s, 2H), 3.40 (s, 3H), 3.13 (t, J=6.9 Hz, 2H), 2.44 (s, 3H).

Example 7(122)

[0957] 1-(4-(2,2,3,3,3-Pentafluoropropyloxy)benzoyl)-2-methylindole-4-acetic Acid

437

[0958] TLC: Rf 0.48 (chloroform:methanol=9:1);

[0959] MS: (APCI, Neg.): 440 (M−H)−;

[0960] NMR (CDCl3): δ 7.72 (d, J=9.0 Hz, 2H), 7.08-6.92 (m, 5H), 6.49 (s, 1H), 3.90 (s, 2H), 3.86 (s, 2H), 2.45 (s, 3H).

Example 7(123)

[0961] 1-(4-(2-(2,6-Difluorophenyl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

438

[0962] TLC: Rf 0.48 (chloroform:methanol=9:1);

[0963] MS: (APCI, Neg.): 448 (M−H)−;

[0964] NMR (CDCl3): δ 7.69 (d, J=9.0 Hz, 2H), 7.08-6.85 (m, 8H), 6.49 (s, 1H), 4.25 (t, J=6.6 Hz, 2H), 3.87 (s, 2H), 3.26-3.16 (m, 2H), 2.44 (s, 3H).

Example 7(124)

[0965] 1-(4-(3-Phenoxybenzyloxy)benzoyl)-2-methylindole-4-acetic Acid

439

[0966] TLC: Rf 0.55 (chloroform:methanol=9:1);

[0967] MS: (APCI, Neg.): 490 (M−H)−;

[0968] NMR (CDCl3): δ 7.71 (d, J=8.7 Hz, 2H), 7.40-6.85 (m, 14H), 6.49 (s, 1H), 5.12 (s, 2H), 3.87 (s, 2H), 2.44 (s, 3H).

Example 7(125)

[0969] 1-(4-Methoxymethyloxybenzoyl)-2-methylindole-4-acetic Acid

440

[0970] TLC: Rf 0.45 (chloroform:methanol=10:1);

[0971] MS: (APCI, Neg.): 352 (M−H)−;

[0972] NMR (CDCl3): δ 7.70 (d, J=9.0 Hz, 2H), 7.09 (d, J=9.0 Hz, 2H), 7.08-6.97 (m, 3H), 6.48 (s, 1H), 5.26 (s, 2H), 3.85 (s, 2H), 3.51 (s, 3H), 2.43 (s, 3H).

Example 7(126)

[0973] 1-(4-(2-(2,5-Dimethyloxazol-4-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

441

[0974] TLC: Rf 0.33 (chloroform:methanol 9:1);

[0975] MS: (APCI, Neg.): 431 (M−H)−;

[0976] NMR (CDCl3): δ 7.67 (d, J=8.7 Hz, 2H), 7.08-6.86 (m, 5H), 6.50 (s, 1H), 4.22 (t, J=6.6 Hz, 2H), 3.86 (s, 2H), 2.90 (t, J=6.6 Hz, 2H), 2.44 (s, 3H), 2.39 (s, 3H), 2.26 (s, 3H).

Example 7(127)

[0977] 1-(4-(2-(4-Methoxy-3-methylphenyl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

442

[0978] TLC: Rf 0.58 (chloroform:methanol=9:1);

[0979] MS: (APCI, Neg.): 456 (M−H)−;

[0980] NMR (CDCl3): δ 7.69 (d, J=9.3 Hz, 2H), 7.11-6.87 (m, 7H), 6.79 (d, J=8.1 Hz, 1H), 6.48 (s, 1H), 4.21 (t, J=7.2 Hz, 2H), 3.86 (s, 2H), 3.82 (s, 3H), 3.05 (t, J=7.2 Hz, 2H), 2.44 (s, 3H), 2.22 (s, 3H).

Example 7(128)

[0981] 1-(4-(2-(3-Ethoxyphenyl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

443

[0982] TLC: Rf 0.56 (chloroform:methanol=9:1);

[0983] MS: (APCI, Neg.): 456 (M−H)−;

[0984] NMR (CDCl3): δ 7.70 (d, J=8.7 Hz, 2H), 7.26-7.20 (m, 1H), 7.08-6.76 (m, 8H), 6.49 (s, 1H), 4.25 (t, J=7.2 Hz, 2H), 4.04 (q, J=7.2 Hz, 2H), 3.87 (s, 2H), 3.11 (t, J=7.2 Hz, 2H), 2.45 (s, 3H), 1.42 (t, J=7.2 Hz, 3H).

Example 7(129)

[0985] 1-(4-(2-(1,3-Dihydrobenzo[c]furan-5-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

444

[0986] TLC: Rf 0.53 (chloroform:methanol=9:1);

[0987] MS: (APCI, Neg.): 454 (M−H)−;

[0988] NMR (CDCl3): δ 7.70 (d, J=8.7 Hz, 2H), 7.22-7.15 (m, 2H), 7.07-6.86 (m, 6H), 6.49 (s, 1H), 5.11 (s, 4H), 4.25 (t, J=6.9 Hz, 2H), 3.87 (s, 2H), 3.16 (t, J=6.9 Hz, 2H), 2.44 (s, 3H).

Example 7(130)

[0989] 1-(4-(2-Buten-1-yloxy)benzoyl)-2-methylindole-4-acetic Acid (Mixture of EZ Form)

445

[0990] TLC: Rf 0.53 (chloroform:methanol=9:1);

[0991] MS: (APCI, Neg.): 362 (M−H)−;

[0992] NMR (CDCl3): δ 7.70 (d, J=9.0 Hz, 2H), 7.10-6.90 (m, 5H), 6.49 (s, 1H), 6.00-5.83 (m, 1H), 5.80-5.70 (m, 1H), 4.55 (d, J=6.0 Hz, 2H), 3.87 (s, 2H), 2.45 (s, 3H), 1.78 (d, J=7.8 Hz, 3H).

Example 7(131)

[0993] 1-(4-(2-(6-Methylpyridin-2-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

446

[0994] TLC: Rf 0.31 (chloroform methanol=10:1);

[0995] MS: (EI, Pos.): 428 (M)+;

[0996] NMR (CDCl3): δ 7.68-7.63 (m, 2H), 7.55 (dd, J=6.6, 6.6 Hz, 1H), 7.11-7.04 (m, 3H), 6.98-6.87 (m, 4H), 6.51 (s, 1H), 4.33 (t, J=6.6 Hz, 2H), 3.86 (s, 2H), 3.26 (t, J=6.6 Hz, 2H), 2.56 (s, 3H), 2.43 (s, 3H).

Example 7(132)

[0997] 1-(4-(2-(3-Methylpyridin-2-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

447

[0998] TLC: Rf 0.32 (chloroform:methanol=10:1);

[0999] MS: (El, Pos.): 428 (M)+;

[1000] NMR (CDCl3): δ 8.43 (dd, J=5.1, 1.2 Hz, 1H), 7.66-7.61 (m, 2H), 7.51 (dd, J=7.5, 1.2 Hz, 1H), 7.13 (dd, J=7.5, 5.1 Hz, 1H), 7.06 (dd, J=7.2, 1.2 Hz, 1H), 6.95 (dd, J=8.1, 7.2 Hz, 1H), 6.91-6.86 (m, 3H), 6.52 (s, 1H), 4.40 (t, J=6.6 Hz, 2H), 3.86 (s, 2H), 3.32 (t, J=6.6 Hz, 2H), 2.42 (s, 3H), 2.41 (s, 3H).

Example 7(133)

[1001] 1-(4-(2-Chloroethyloxy)benzoyl)-2-methylindole-4-acetic Acid

448

[1002] TLC: Rf 0.53 (chloroform:methanol=9:1);

[1003] MS: (APCI, Neg.): 370 (M−H)−;

[1004] NMR (CDCl3): δ 7.72 (d, J=9.3 Hz, 2H), 7.08-6.88 (m, 5H), 6.50 (s, 1H), 4.32 (t, J=6.0 Hz, 2H), 3.90-3.84 (m, 4H), 2.45 (s, 3H).

Example 7(134)

[1005] 1-(4-(2-(Benzo[b]thiophen-3-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

449

[1006] TLC: Rf 0.50 (chloroform:methanol=9:1);

[1007] MS: (APCI, Neg.): 468 (M−H)−;

[1008] NMR (CDCl3): δ 7.91-7.80 (m, 2H), 7.70 (d, J=8.7 Hz, 2H), 7.46-7.30 (m, 2H), 7.30-7.24 (m, 1H), 7.08-6.88 (m, 5H), 6.48 (s, 1H), 4.38 (t, J=6.9 Hz, 2H), 3.87 (s, 2H), 3.40 (t, J=6.9 Hz, 2H), 2.44 (s, 3H).

Example 7(135)

[1009] 1-(4-Ethoxymethyloxybenzoyl)-2-methylindole-4-acetic Acid

450

[1010] TLC: Rf 0.45 (chloroform:methanol=10:1);

[1011] MS: (APCI, Neg.): 366 (M−H)−;

[1012] NMR (CDCl3): δ 7.63 (d, J=8.8 Hz, 2H), 7.05-6.90 (m, 5H), 6.41 (d, J=0.8 Hz, 1H), 5.24 (s, 2H), 3.79 (s, 2H), 3.67 (q, J=7.2 Hz, 2H), 2.36 (d, J=0.8 Hz, 3H), 1.16 (t, J=7.2 Hz, 3H).

Example 7(136)

[1013] 1-(4-Acetyloxybenzoyl)-2-methylindole-4-acetic Acid

451

[1014] TLC: Rf 0.53 (chloroform:methanol=9:1);

[1015] MS: (APCI, Neg.): 350 (M−H)−;

[1016] NMR (CDCl3): δ 7.77 (d, J=8.7 Hz, 2H), 7.28-7.17 (m, 2H), 7.10-6.94 (m, 3H), 6.51 (s, 1H), 3.87 (s, 2H), 2.43 (s, 3H), 2.35 (s, 3H).

Example 7(137)

[1017] 1-(4-(2-Propyn-1-yloxy)benzoyl)-2-methylindole-4-acetic Acid

452

[1018] TLC: Rf 0.59 (chloroform:methanol=9:1);

[1019] MS: (APCI, Neg.): 346 (M−H)−;

[1020] NMR (CDCl3): δ 7.73 (d, J=9.0 Hz, 2H), 7.09-6.90 (m, 5H), 6.50 (s, 1H), 4.79 (d, J=2.4 Hz, 2H), 3.87 (s, 2H), 2.58 (t, J=2.4 Hz, 1H), 2.45 (s, 3H).

Example 7(138)

[1021] 1-(4-(2-Propen-1-yloxy)benzoyl)-2-methylindole-4-acetic Acid

453

[1022] TLC: Rf 0.45 (chloroform:methanol=9:1);

[1023] MS: (APCI, Neg.): 348 (M−H)−;

[1024] NMR (CDCl3): δ 7.71 (d, J=8.7 Hz, 2H), 7.10-6.90 (m, 5H), 6.49 (s, 1H), 6.15-6.00 (m, 1H), 5.50-5.40 (m, 1H), 5.40-5.30 (m, 1H), 4.65-4.60 (m, 2H), 3.87 (s, 2H), 2.45 (s, 3H).

Example 7(139)

[1025] 1-(4-(2-Butyn-1-yloxy)benzoyl)-2-methylindole-4-acetic Acid

454

[1026] TLC: Rf 0.50 (chloroform:methanol=9:1);

[1027] MS: (APCI, Neg.): 360 (M−H)−;

[1028] NMR (CDCl3): δ 7.72 (d, J=9.0 Hz, 2H), 7.08-6.92 (m, 5H), 6.49 (s, 1H), 4.78-4.70 (m, 2H), 3.87 (s, 2H), 2.45 (s, 3H), 1.88 (t, J=2.4 Hz, 3H).

Example 7(140)

[1029] 1-(4-(3-Penten-1-yloxy)benzoyl)-2-methylindole-4-acetic Acid

455

[1030] TLC: Rf 0.51 (chloroform:methanol=10:1);

[1031] MS: (APCI, Neg.): 376 (M−H)−;

[1032] NMR (CDCl3): δ 7.70 (dd, J=6.9, 2.4 Hz, 2H), 7.05-6.92 (m, 5H), 6.48 (d, J=0.6 Hz, 1H), 5.70-5.40 (m, 2H), 4.05 (t, J=6.6 Hz, 2H), 3.86 (s, 2H), 2.52 (m, 2H), 2.44 (d, J=0.6 Hz, 3H), 1.69 (m, 3H).

Example 7(141)

[1033] 1-(4-(2-(1-Methylindol-3-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

456

[1034] TLC: Rf 0.53 (chloroform:methanol=10:1);

[1035] MS: (APCI, Neg.): 465 (M−H)−;

[1036] NMR (CDCl3): δ 7.70-7.63 (m, 3H), 7.35-7.20 (m, 2H), 7.14 (m, 1H), 7.03 (m, 1H), 7.05-6.93 (m, 5H), 6.47 (d, J=1.2 Hz, 1H), 4.29 (t, J=6.9 Hz, 2H), 3.85 (s, 2H), 3.77 (s, 3H), 3.28 (t, J=6.9 Hz, 2H), 2.43 (d, J=1.2 Hz, 3H).

Example 7(142)

[1037] 1-(4-(2-(1,2,3,4-Tetrahydronaphthalen-2-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

457

[1038] TLC: Rf 0.53 (chloroform:methanol=10:1);

[1039] MS: (APCI, Neg.): 452 (M−H)−;

[1040] NMR (CDCl3): δ 7.72 (dd, J=6.9, 1.8 Hz, 2H), 7.12-7.10 (m, 4H), 7.04 (m, 1H), 7.03-6.95 (m, 4H), 6.49 (s, 1H), 4.02 (d, J=6.3 Hz, 2H), 3.87 (s, 2H), 3.01 (dd, J=14, 4.2 Hz, 1H), 2.92-2.87 (m, 2H), 2.68 (dd, J=14, 10.5 Hz, 1H), 2.45 (s, 3H), 2.35 (m, 1H), 2.10 (m, 1H), 1.65 (m, 1H).

Example 7(143)

[1041] 1-(4-(2-(1,2,3,4-Tetrahydroquinolin-1-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

458

[1042] TLC: Rf 0.51 (chloroform:methanol=10:1);

[1043] MS: (APCI, Neg.): 467 (M−H)−;

[1044] NMR (CDCl3): δ 7.70 (d, J=8.7 Hz, 2H), 7.15-6.90 (m, 7H), 6.65-6.55 (m, 2H), 6.47 (s, 1H), 4.22 (t, J=5.7 Hz, 2H), 3.84 (s, 2H), 3.73 (t, J=5.7 Hz, 2H), 3.44 (t, J=5.7 Hz, 2H), 2.76 (t, J=5.7 Hz, 2H), 2.43 (s, 3H), 2.00-1.90 (m, 2H).

Example 7(144)

[1045] 1-(4-(2-Hyd roxy-(1-hydroxymethyl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

459

[1046] TLC: Rf 0.12 (chloroform methanol=9:1);

[1047] MS: (APCI, Neg.): 382 (M−H)−;

[1048] NMR (CDCl3): δ 7.70 (d, J=8.7 Hz, 2H), 7.10-6.90 (m, 5H), 6.52 (s, 1H), 4.58-4.48 (m, 1H), 3.90 (d, J=6.0 Hz, 4H), 3.83 (s, 2H), 2.44 (s, 3H).

Example 7(145)

[1049] 1-(4-(2-(2-Ethylphenyl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

460

[1050] TLC: Rf 0.35 (chloroform:methanol=10:1);

[1051] MS: (APCI, Neg.): 440 (M−H)−;

[1052] NMR (CDCl3): δ 7.72-7.67 (m, 2H), 7.26-7.15 (m, 3H), 7.06-6.90 (m, 6H), 6.49 (d, J=0.9 Hz, 1H), 4.23 (t, J=7.5 Hz, 2H), 3.87 (s, 2H), 3.18 (t, J=7.5 Hz, 2H), 2.74 (q, J=7.5 Hz, 2H), 2.44 (d, J=0.9 Hz, 3H), 1.27 (t, J=7.5 Hz, 3H).

Example 7(146)

[1053] 1-(4-(2-(2-Methoxymethylphenyl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

461

[1054] TLC: Rf 0.34 (chloroform:methanol=10:1);

[1055] MS: (FAB, Pos.): 458 (M+H)+;

[1056] NMR (CDCl3): δ 7.71-7.67 (m, 2H), 7.37-7.23 (m, 3H), 7.06-6.93 (m, 6H), 6.48 (s, 1H), 4.54 (s, 2H), 4.27 (t, J=7.5 Hz, 2H), 3.86 (s, 2H), 3.41 (s, 3H), 3.21 (t, J=7.5 Hz, 2H), 2.44 (d, J=0.6 Hz, 3H).

Example 7(147)

[1057] 1-(4-(3,4-Dihydro-2H-benzo[b]pyran-3-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

462

[1058] TLC: Rf 0.34 (chloroform:methanol=10:1);

[1059] MS: (APCI, Neg.): 454 (M−H)−;

[1060] NMR (CDCl3): δ 7.72-7.43 (m, 5H), 7.15-6.82 (m, 6H), 6.49 (s, 1H), 4.36 (m, 1H), 4.17 (m, 1H), 4.08 (d, J=6.9 Hz, 2H), 3.87 (s, 2H), 3.04 (dd, J=16.5, 6.0 Hz, 1H), 2.78 (dd, J=16.5, 7.2 Hz, 1H), 2.63 (m, 1H), 2.44 (d, J=1.2 Hz, 3H).

Example 7(148)

[1061] 1-(4-(Indan-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

463

[1062] TLC: Rf 0.35 (chloroform methanol=10:1);

[1063] MS: (FAB, Pos.):440 (M+H)+;

[1064] NMR (CDCl3): δ 7.73-7.68 (m, 2H), 7.26-6.93 (m, 9H), 6.49 (s, 1H), 4.04 (d, J=6.9 Hz, 2H), 3.87 (s, 2H), 3.19 (dd, J=16.5, 7.5 Hz, 2H), 3.02 (m, 1H), 2.89 (dd, J=16.5, 6.0 Hz, 2H), 2.44 (d, J=1.2 Hz, 3H).

Example 7(149)

[1065] 1-(4-(2-(1,4-Benzodioxan-2-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

464

[1066] TLC: Rf 0.44 (chloroform:methanol=9:1);

[1067] MS: (APCI, Neg.): 470 (M−H)−;

[1068] NMR (CDCl3): δ 7.71 (d, J=8.7 Hz, 2H), 7.10-6.80 (m, 9H), 6.49 (s, 1H), 4.50-4.40 (m, 1H), 4.38-4.17 (m, 3H), 4.01 (dd, J=11.4, 7.2 Hz, 1H), 3.86 (s, 2H), 2.44 (s, 3H), 2.17 (q, J=6.0 Hz, 2H).

Example 7(150)

[1069] 1-(4-(3,4-Dihydro-2H-benzo[b]pyran-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

465

[1070] TLC: Rf 0.49 (chloroform:methanol=10:1);

[1071] MS: (APCI, Neg.): 454 (M−H)−;

[1072] NMR (CDCl3): δ 7.74-7.67 (m, 2H), 7.06-6.87 (m, 9H), 6.49 (s, 1H), 4.45 (m, 1H), 4.38-4.15 (m, 2H), 3.86 (s, 2H), 3.00-2.80 (m, 2H), 2.44 (s, 3H), 2.30-1.90 (m, 2H).

Example 7(151)

[1073] 1-(4-(3,4-Dihydro-2H-1,4-benzoxazin-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

466

[1074] TLC: Rf 0.25 (chloroform:methanol=10:1);

[1075] MS: (APCI, Neg.): 455 (M−H)−;

[1076] NMR (CDCl3): δ 7.76-7.40 (m, 3H), 7.10-6.89 (m, 4H), 6.89-6.60 (m, 4H), 6.49 (s, 1H), 4.60 (m, 1H), 4.31 (dd, J=9.8, 5.0 Hz, 1H), 4.24 (dd, J=9.8, 6.2 Hz, 1H), 3.86 (s, 2H), 3.58 (dd, J=11.8, 3.0 Hz, 1H), 3.42 (dd, J=11.8, 6.6 Hz, 1H), 2.44 (s, 3H).

Example 7(152)

[1077] 1-(4-(4-Methyl-3,4-dihydro-2H-1,4-benzoxazin-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

467

[1078] TLC: Rf 0.26 (chloroform:methanol=10:1);

[1079] MS: (APCI, Neg.): 469 (M−H)−;

[1080] NMR (CDCl3): δ 7.78-7.40 (m, 3H), 7.10-6.78 (m, 6H), 6.73 (d, J=8.0 Hz, 2H), 6.49 (s, 1H), 4.68 (m, 1H), 4.31 (dd, J=10.0, 5.2 Hz, 1H), 4.20 (dd, J=10.0, 6.4 Hz, 1H), 3.86 (s, 2H), 3.41 (dd, J=11.6, 2.8 Hz, 1H), 3.27 (dd, J=11.6, 6.6 Hz, 1H), 2.92 (s, 3H), 2.44 (s, 3H).

Example 7(153)

[1081] 1-(4-(1,3-Dioxaindan-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

468

[1082] TLC: Rf 0.33 (chloroform:methanol=10:1);

[1083] MS: (FAB, Pos.): 444 (M+H)+;

[1084] NMR (CDCl3): δ 7.74-7.69 (m, 2H), 7.06-6.85 (m, 9H), 6.50-6.47 (m, 2H), 4.35 (d, J=4.2 Hz, 2H), 3.85 (s, 2H), 2.43 (d, J=0.9 Hz, 3H).

Example 7(154)

[1085] 1-(4-(Benzo[b]furan-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

469

[1086] TLC: Rf 0.38 (chloroform:methanol=10:1);

[1087] MS: (FAB, Pos.): 440 (M+H)+;

[1088] NMR (CDCl3): δ 7.76-7.71 (m, 2H), 7.59 (m, 1H), 7.51 (m, 1H), 7.32 (m, 1H), 7.25 (m, 1H), 7.11-6.92 (m, 5H), 6.84 (d, J=0.6 Hz, 1H), 6.49 (m, 1H), 5.26 (s, 2H), 3.87 (s, 2H), 2.45 (d, J=1.2 Hz, 3H).

Example 7(155)

[1089] 1-(4-(2,3-Dihydrobenzo[b]furan-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

470

[1090] TLC: Rf 0.34 (chloroform:methanol=10:1);

[1091] MS: (El, Pos.): 441 (M)+;

[1092] NMR (CDCl3): δ 7.73-7.69 (m, 2H), 7.23-7.12 (m, 2H), 7.06-6.82 (m, 7H), 6.49 (d, J=1.2 Hz, 1H), 5.20 (m, 1H), 4.29 (dd, J=9.9, 6.3 Hz, 1H), 4.20 (dd, J=9.9, 4.2 Hz, 1H), 3.86 (s, 2H), 3.42 (dd, J=15.9, 9.6 Hz, 1H), 3.17 (dd, J=15.9, 8.4 Hz, 1H), 2.44 (d, J=1.2 Hz, 3H).

Example 7(156)

[1093] 1-(4-(2-(2,5-Dimethoxyphenyl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

471

[1094] TLC: Rf 0.50 (chloroform:methanol=10:1);

[1095] MS: (FAB, Pos.): 474 (M+H)+;

[1096] NMR (CDCl3): δ 7.69 (m, 2H), 7.08-6.92 (m, 5H), 6.86-6.72 (m, 3H), 6.48 (s, 1H), 4.24 (t, J=6.8 Hz, 2H), 3.86 (s, 2H), 3.81 (s, 3H), 3.77 (s, 3H), 3.12 (t, J=6.8 Hz, 2H), 2.44 (s, 3H).

Example 7(157)

[1097] 1-(4-(2,3-Dihydrobenzo[b]furan-3-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

472

[1098] TLC: Rf 0.45 (chloroform:methanol=10:1);

[1099] MS: (FAB, Pos.): 442 (M+H)+;

[1100] NMR (CDCl3): δ 7.70 (m, 2H), 7.31 (d, J=7.4 Hz, 1H), 7.21 (m, 1H), 7.10-6.82 (m, 7H), 6.49 (s, 1H), 4.73 (t, J=9.6 Hz, 1H), 4.55 (dd, J=9.6, 4.6 Hz, 1H), 4.29-3.88 (m, 3H), 3.86 (s, 2H), 2.44 (s, 3H).

Example 7(158)

[1101] 1-(4-(2-Cyclopropyloxyethyloxy)benzoyl)-2-methylindole-4-acetic Acid

473

[1102] TLC: Rf 0.42 (chloroform:methanol=10:1);

[1103] MS: (FAB, Pos.): 394 (M+H)+;

[1104] NMR (CDCl3): δ 7.71 (m, 2H), 7.12-6.88 (m, 5H), 6.49 (s, 1H), 4.19 (t, J=4.6 Hz, 2H), 3.97-3.82 (m, 4H), 3.42 (m, 1H), 2.44 (s, 3H), 0.72-0.58 (m, 2H), 0.58-0.46 (m, 2H).

Example 7(159)

[1105] 1-(4-(2-(2,4-Dimethylphenyl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

474

[1106] TLC: Rf 0.50 (chloroform:methanol=9:1);

[1107] MS: (APCI, Neg.): 440 (M−H)−;

[1108] NMR (CDCl3): δ 7.69 (d, J=9.0 Hz, 2H), 7.12 (d, J=7.5 Hz, 1H), 7.08-6.90 (m, 7H), 6.49 (s, 1H), 4.20 (t, J=7.5 Hz, 2H), 3.87 (s, 2H), 3.12 (t, J=7.5 Hz, 2H), 2.45 (s, 3H), 2.36 (s, 3H), 2.31 (s, 3H).

Example 7(160)

[1109] 1-(4-(2-(2,6-Dimethylphenyl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

475

[1110] TLC: Rf 0.59 (chloroform:methanol=9:1);

[1111] MS: (APCI, Neg.): 440 (M−H)−;

[1112] NMR (CDCl3): δ 7.70 (d, J=9.0 Hz, 2H), 7.09-6.90 (m, 8H), 6.49 (s, 1H), 4.13 (t, J=7.2 Hz, 2H), 3.88 (s, 2H), 3.22 (t, J=7.2 Hz, 2H), 2.45 (s, 3H), 2.41 (s, 6H).

Example 7(161)

[1113] 1-(4-(2-(Benzo[b]thiophen-2-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

476

[1114] TLC: Rf 0.61 (chloroform:methanol=9:1);

[1115] MS: (APCI, Neg.): 468 (M−H)−;

[1116] NMR (CDCl3): δ 7.82-7.76 (m, 1H), 7.75-7.68 (m, 3H), 7.37-7.24 (m, 2H), 7.16 (s, 1H), 7.08-6.92 (m, 5H), 6.49 (s, 1H), 4.36 (t, J=6.3 Hz, 2H), 3.87 (s, 2H), 3.43 (t, J=6.3 Hz, 2H), 2.44 (s, 3H).

Example 7(162)

[1117] 1-(4-(2-(2-Methoxyphenyloxy)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

477

[1118] TLC: Rf 0.52 (chloroform:methanol=10:1);

[1119] MS: (APCI, Neg.): 458 (M−H)−;

[1120] NMR (CDCl3): δ 7.70 (d, J=9.0 Hz, 2H), 7.03-6.92 (m, 9H), 6.48 (d, J=0.9 Hz, 1H), 4.42 (s, 4H), 3.85 (s, 3H), 3.84 (s, 2H), 2.44 (d, J=0.9 Hz, 3H).

Example 7(163)

[1121] 1-(4-(2-(N-Ethyl-N-phenylamino)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid Acetate

478

[1122] TLC: Rf 0.50 (chloroform:methanol 10:1);

[1123] MS: (APCI, Neg.): 455 (M−H)−;

[1124] NMR (CDCl3): δ 7.67 (d, J=9.0 Hz, 2H), 7.26-7.20 (m, 2H), 7.04-6.88 (m, 5H), 6.76-6.66 (m, 3H), 6.45 (d, J=0.9 Hz, 1H), 4.17 (d, J=6.8 Hz, 2H), 3.83 (s, 2H), 3.74 (t, J=6.8 Hz, 2H), 3.47 (q, J=7.2 Hz, 2H), 2.42 (d, J=0.9 Hz, 3H), 2.06 (s, 3H), 1.19 (t, J=7.2 Hz, 3H).

Example 7(164)

[1125] 1-(4-(2-(Indol-1-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

479

[1126] TLC: Rf 0.50 (chloroform:methanol=10:1);

[1127] MS: (APCI, Neg.): 451 (M−H)−;

[1128] NMR (CDCl3): δ 7.68-7.63 (m, 3H), 7.41 (d, J=8.0 Hz, 1H), 7.26-7.21 (m, 2H), 7.14-6.86 (m, 8H), 6.54 (dd, J=3.0, 0.6 Hz, 1H), 6.48 (s, 1H), 4.58 (t, J=5.4 Hz, 2H), 4.36 (t, J=5.4 Hz, 2H), 3.86 (s, 2H), 2.42 (s, 3H).

Example 7(165)

[1129] 1-(4-(2-(3-Methylpyridin-2-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

480

[1130] TLC: Rf 0.44 (chloroform:methanol=10:1);

[1131] MS: (APCI, Neg.): 427 (M−H)−;

[1132] NMR (CDCl3): δ 8.43 (m, 1H), 7.64 (d, J=6.9 Hz, 2H), 7.49 (m, 1H), 7.21 (d, J=8.1 Hz, 1H), 7.05 (d, J=8.1 Hz, 1H), 7.00-6.85 (m, 4H), 6.53 (d, J=0.9 Hz, 1H), 4.33 (t, J=6.6 Hz, 2H), 3.85 (s, 2H), 3.26 (t, J=6.6 Hz, 2H), 2.41 (d, J=0.9 Hz, 3H), 2.31 (s, 3H).

Example 7(166)

[1133] 1-(4-(2-(Benzo[b]furan-2-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

481

[1134] TLC: Rf 0.50 (chloroform:methanol=9:1);

[1135] MS: (APCI, Neg.): 452 (M−H)−;

[1136] NMR (CDCl3): δ 7.76-7.42 (m, 4H), 7.30-7.17 (m, 2H), 7.10-6.90 (m, 5H), 6.57 (s, 1H), 6.49 (s, 1H), 4.42 (t, J=6.6 Hz, 2H), 3.87 (s, 2H), 3.32 (t, J=6.6 Hz, 2H), 2.44 (s, 3H).

Example 7(167)

[1137] 1-(4-(4-Methyl-3,4-dihydro-2H-1,4-benzoxazin-3-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

482

[1138] TLC: Rf 0.37 (chloroform:methanol=10:1);

[1139] MS: (APCI, Neg.): 469 (M−H)−;

[1140] NMR (CDCl3): δ 7.72-7.67 (m, 2H), 7.06-6.81 (m, 7H), 6.69-6.62 (m, 2H), 6.49 (m, 1H), 4.48 (dd, J=11.1, 1.8 Hz, 1H), 4.14 (d, J=7.5 Hz, 2H), 4.13 (dd, J=11.1, 2.4 Hz, 1H), 3.86 (s, 2H), 3.74 (m, 1H), 3.08 (s, 3H), 2.44 (d, J=1.2 Hz, 3H).

Example 7(168)

[1141] 1-(4-(2-(2,4-Dimethoxyphenyloxy)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

483

[1142] TLC: Rf 0.52 (chloroform:methanol 10:1);

[1143] MS: (APCI, Neg.): 488 (M−H)−;

[1144] NMR (CDCl3): δ 7.72-7.62 (m, 3H), 7.58-7.50 (m, 1H), 7.49-7.41 (m, 1H), 7.06-6.85 (m, 4H), 6.53-6.48 (m, 2H), 6.39 (dd, J=8.7, 2.7 Hz, 1H), 4.45-4.30 (m, 4H), 3.85 (s, 2H), 3.83 (s, 3H), 3.78 (s, 3H), 2.44 (d, J=0.9 Hz, 3H).

Example 7(169)

[1145] 1-(4-(2-(4-Methylpyrid in-2-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

484

[1146] TLC: Rf 0.44 (chloroform:methanol=10:1);

[1147] MS: (APCI, Neg.): 427 (M−H)−;

[1148] NMR (CDCl3): δ 8.44 (d, J=6.6 Hz, 1H), 7.64 (d, J=8.7 Hz, 2H), 7.13-6.86 (m, 7H), 6.52 (d, J=0.8 Hz, 1H), 4.34 (t, J=6.2 Hz, 2H), 3.85 (s, 2H), 3.26 (t, J=6.2 Hz, 2H), 2.41 (d, J=0.8 Hz, 3H), 2.31 (s, 3H).

Example 7(170)

[1149] 1-(4-(4-Ethyl-3,4-dihydro-2H-1,4-benzoxazin-3-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

485

[1150] TLC: Rf 0.28 (chloroform:methanol=10:1);

[1151] MS: (APCI, Neg.): 483 (M−H)−;

[1152] NMR (CDCl3): δ 7.80-7.57 (m, 2H), 7.10-6.79 (m, 7H), 6.79-6.56 (m, 2H), 6.49 (s, 1H), 4.68-4.50 (m, 1H), 4.31 (dd, J=9.6, 5.2 Hz, 1H), 4.21 (dd, J=9.6, 6.2 Hz, 1H), 3.86 (s, 2H), 3.57-3.20 (m, 4H), 2.44 (s, 3H), 1.17 (t, J=7.4 Hz, 3H).

Example 7(171)

[1153] 1-(4-(2-(N-Methyl-N-(3-methylphenyl)amino)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

486

[1154] TLC: Rf 0.27 (chloroform:methanol=10:1);

[1155] MS: (APCI, Neg.): 455 (M−H)−;

[1156] NMR (CDCl3): δ 7.68 (d, J=8.8 Hz, 2H), 7.21-6.87 (m, 6H), 6.63-6.52 (m, 3H), 6.48 (s, 1H), 4.22 (t, J=6.0 Hz, 2H), 3.85 (s, 2H), 3.79 (t, J=6.0 Hz, 2H), 3.06 (s, 3H), 2.43 (s, 3H), 2.32 (s, 3H).

Example 7(172)

[1157] 1-(4-(3,4-Dihydro-2H-1,5-benzodioxepin-3-yloxy)benzoyl)-2-methylindole-4-acetic Acid

487

[1158] TLC: Rf 0.54 (chloroform:methanol=9:1);

[1159] MS: (APCI, Neg.): 456 (M−H)−;

[1160] NMR (CDCl3): δ 7.78-7.42 (m, 6H), 7.10-6.90 (m, 5H), 6.50 (s, 1H), 5.08-4.96 (m, 1H), 4.57 (dd, J=12.6, 4.2 Hz, 2H), 4.47 (dd, J=12.6, 4.2 Hz, 2H), 3.87 (s, 2H), 2.45 (s, 3H).

Example 7(173)

[1161] 1-(4-(3,4-Dihydro-2H-1,5-benzodioxepin-3-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

488

[1162] TLC: Rf 0.50 (chloroform:methanol=9:1);

[1163] MS: (APCI, Neg.): 470 (M−H)−;

[1164] NMR (CDCl3): δ 7.78-7.42 (m, 5H), 7.10-6.90 (m, 6H), 6.50 (s, 1H), 4.40-4.28 (m, 4H), 4.26 (d, J=6.9 Hz, 2H), 3.87 (s, 2H), 2.80-2.70 (m,1H), 2.45 (s, 3H).

Example 7(174)

[1165] 1-(4-(1,4-Benzodioxan-6-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

489

[1166] TLC: Rf 0.40 (chloroform:methanol=10:1);

[1167] MS: (EI, Pos.): 457 (M)+;

[1168] NMR (CDCl3): δ 7.73-7.68 (m, 2H), 7.07-6.90 (m, 8H), 6.49 (s, 1H), 5.03 (s, 2H), 4.27 (s, 4H), 3.87 (s, 2H), 2.45 (d, J=0.9 Hz, 3H).

Example 7(175)

[1169] 1-(4-(2-(4-Methoxy-2-methylphenyl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

490

[1170] TLC: Rf 0.37 (chloroform:methanol=10:1);

[1171] MS: (El, Pos.): 457 (M)+;

[1172] NMR (CDCl3): δ 7.72-7.67 (m, 2H), 7.15 (d, J=8.1 Hz, 1H), 7.06-6.91 (m, 5H), 6.76-6.71 (m, 2H), 6.49 (s, 1H), 4.18 (t, J=7.2 Hz, 2H), 3.86 (s, 2H), 3.79 (s, 3H), 3.09 (t, J=7.2 Hz, 2H), 2.44 (d, J=0.9 Hz, 3H) 2.37 (s, 3H).

Example 7(176)

[1173] 1-(4-(1-Methyl-1,2,3,4-tetrahydroquinolin-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

491

[1174] TLC: Rf 0.39 (chloroform:methanol=10:1);

[1175] MS: (EI, Pos.): 468 (M)+;

[1176] NMR (CDCl3): δ 7.72-7.67 (m, 2H), 7.12 (m, 1H), 7.06-6.91 (m, 6H), 6.68-6.58 (m, 2H), 6.49 (m, 1H), 4.13 (dd, J=9.3, 5.7 Hz, 1H), 4.00 (dd, J=9.3, 7.5 Hz, 1H), 3.86 (s, 2H), 3.79 (m, 1H), 3.07 (s, 3H), 2.89-2.70 (m, 2H), 2.44 (d, J=0.9 Hz, 3H) 2.19 (m, 1H), 2.02 (m, 1H).

Example 7(177)

[1177] 1-(4-(2-(2,3-Dihydrobenzo[b]furan-2-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

492

[1178] TLC: Rf 0.50 (chloroform:methanol=9:1);

[1179] MS: (APCI, Neg.): 454 (M−H)−;

[1180] NMR (CDCl3): δ 7.72 (d, J=8.7 Hz, 2H), 7.22-6.76 (m, 9H), 6.50 (s, 1H), 5.10-5.00 (m, 1H), 4.40-4.20 (m, 2H), 3.88 (s, 2H), 3.41 (dd, J=15.6, 8.4 Hz, 1H), 2.97 (dd, J=15.6, 7.5 Hz, 1H), 2.46 (s, 3H), 2.35-2.15 (m, 2H).

Example 7(178)

[1181] 1-(4-(4,7-Dimethyl-3,4-dihydro-2H-1,4-benzoxazin-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

493

[1182] TLC: Rf 0.48 (chloroform:methanol=10:1);

[1183] MS: (APCI, Neg.): 483 (M−H)−;

[1184] NMR (CDCl3): δ 7.69 (dd, J=8.8, 2.2 Hz, 2H), 7.04-6.90 (m, 6H), 6.70-6.63 (m, 2H), 6.48 (s, 1H), 4.65 (m, 1H), 4.28 (dd, J=7.2, 5.1 Hz, 1H), 4.23 (dd, J=7.2, 2.5 Hz, 1H), 3.85 (s, 2H), 3.32 (dd, J=12.4, 2.6 Hz, 1H), 3.20 (dd, J=12.4, 6.6 Hz, 1H), 2.87 (s, 3H), 2.44 (s, 3H), 2.23 (s, 3H).

Example 7(179)

[1185] 1-(4-(4,6-Dimethyl-3,4-dihydro-2H-1,4-benzoxazin-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

494

[1186] TLC: Rf 0.48 (chloroform:methanol=10:1);

[1187] MS: (APCI, Neg.): 483 (M−H)−;

[1188] NMR (CDCl3): δ 7.69 (m, 2H), 7.04-6.90 (m, 6H), 6.73 (d, J=8.0 Hz, 1H), 6.53 (s, 1H), 6.48 (s, 1H), 4.65 (m, 1H), 4.28 (dd, J=7.2, 5.1 Hz, 1H), 4.22 (dd, J=7.2, 2.5 Hz, 1H), 3.85 (s, 2H), 3.35 (dd, J=12.2, 3.0 Hz, 1H), 3.25 (dd, J=12.2, 6.2 Hz, 1H), 2.90 (s, 3H), 2.44 (s, 3H), 2.27 (s, 3H).

Example 7(180)

[1189] 1-(4-(1-Methylindolin-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

495

[1190] TLC: Rf 0.49 (chloroform:methanol=9:1);

[1191] MS: (APCI, Neg.): 453 (M−H)−;

[1192] NMR (CDCl3): δ 7.76-7.66 (m, 2H), 7.20-6.46 (m, 10H), 5.00-2.80 (m, 5H), 3.87 (s, 2H), 2.94 and 2.91 (each s, total 3H), 2.45 (s, 3H).

Example 7(181)

[1193] 1-(4-(4,5-Dimethyl-3,4-dihydro-2H-1,4-benzoxazin-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

496

[1194] TLC: Rf 0.51 (chloroform:methanol=9:1);

[1195] MS: (APCI, Neg.): 483 (M−H)−;

[1196] NMR (CDCl3): δ 7.74 (d, J=9.0 Hz, 2H), 7.08-6.84 (m, 6H), 6.82-6.75 (m, 2H), 6.50 (s, 1H), 4.55-4.45 (m, 1H), 4.36 (dd, J=9.9, 4.5 Hz, 1H), 4.22 (dd, J=9.9, 4.5 Hz, 1H), 3.87 (s, 2H), 3.27 (dd, J=13.8, 2.4 Hz, 1H), 3.08 (dd, J=13.8, 9.9 Hz, 1H), 2.78 (s, 3H), 2.45 (s, 3H), 2.33 (s, 3H).

Example 7(182)

[1197] 1-(4-(4-Acetyl-3,4-dihydro-2H-1,4-benzoxazin-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

497

[1198] TLC: Rf 0.50 (chloroform:methanol=10:1);

[1199] MS: (APCI, Neg.): 497 (M−H)−;

[1200] NMR (CDCl3): δ 7.75-7.62 (m, 4H), 7.15-6.90 (m, 7H), 6.49 (s, 1H), 4.64 (brs, 2H), 4.25 (m, 2H), 3.86 (s, 2H), 3.60 (brs 1H), 2.44 (s, 3H), 2.35 (s, 3H).

Example 7(183)

[1201] 1-(4-(3-Acetyl-2,3-dihydro-1,3-benzoxazol-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

498

[1202] TLC: Rf 0.34 (chloroform:methanol=10:1);

[1203] MS: (FAB, Pos.):485 (M+H)+;

[1204] NMR (CDCl3): δ 7.67 (d, J=9.3 Hz, 2H), 7.10-6.90 (m, 9H), 6.66 (brs, 1H), 6.48 (s, 1H), 4.40 (brs, 2H), 3.86 (s, 2H), 2.43 (s, 3H), 2.43 (d, J=0.9 Hz, 3H).

Example 7(184)

[1205] 1-(4-(4,6,8-Trimethyl-3,4-dihydro-2H-1,4-benzoxazin-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

499

[1206] TLC: Rf 0.36 (chloroform:methanol=10:1);

[1207] MS: (APCI, Neg.): 497 (M−H)−;

[1208] NMR (CDCl3): δ 7.74-7.69 (m, 2H), 7.07-6.93 (m, 5H), 6.49 (s, 1H), 6.40 (s, 1H), 6.40 (s, 1H), 4.65 (m, 1H), 4.31 (dd, J=9.9, 4.8 Hz, 1H), 4.21 (dd, J=9.9, 6.3 Hz, 1H), 3.87 (s, 2H), 3.39 (dd, J=11.7, 2.7 Hz, 1H), 3.24 (dd, J=11.7, 6.0 Hz, 1H), 2.89 (s, 3H), 2.45 (d, J=0.6 Hz, 3H), 2.24 (s, 3H), 2.14 (s, 3H).

Example 7(185)

[1209] 1-(4-((3Z)-3-Hexen-1-yloxy)benzoyl)-2-methylindole-4-acetic Acid

500

[1210] TLC: Rf 0.52 (chloroform:methanol=10:1);

[1211] MS: (APCI, Neg.): 390 (M−H)−;

[1212] NMR (CDCl3): δ 7.70 (dd, J=6.9, 2.1 Hz, 2H), 7.06-6.92 (m, 5H), 6.48 (d, J=0.9 Hz, 1H), 5.56 (m, 1H), 5.40 (m, 1H), 4.05 (t, J=6.9 Hz, 2H), 3.86 (s, 2H), 2.57 (m, 2H), 2.44 (d, J=0.9 Hz, 3H), 2.11 (m, 2H), 1.00 (t, J=7.2 Hz, 3H).

Example 7(186)

[1213] 1-(4-(4-Methyl-1,3-dioxaindan-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

501

[1214] TLC: Rf 0.52 (chloroform:methanol=10:1);

[1215] MS: (APCI, Neg.): 456 (M−H)−;

[1216] NMR (CDCl3): δ 7.71 (dd, J=6.9, 2.1 Hz, 2H), 7.04-6.95 (m, 5H), 6.80-6.67 (m, 2H), 6.48-6.44 (m, 2H), 4.35 (d, J=4.2 Hz, 2H), 3.85 (s, 2H), 2.44 (d, J=0.9 Hz, 3H), 2.23 (s, 3H).

Example 7(187)

[1217] 1-(4-(5-Methyl-1,3-d ioxaindan-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

502

[1218] TLC: Rf 0.52 (chloroform:methanol=10:1);

[1219] MS: (APCI, Neg.): 456 (M−H)−;

[1220] NMR (CDCl3): δ 7.71 (m, 2H), 7.06-6.92 (m, 6H), 6.75-6.65 (m, 2H), 6.49-6.44 (m, 2H), 4.32 (d, J=4.2 Hz, 2H), 3.86 (s, 2H), 2.44 (d, J=0.9 Hz, 3H), 2.29 (s, 3H).

Example 7(188)

[1221] 1-(4-((4E)-4-Hexen-1-yloxy)benzoyl)-2-methylindole-4-acetic Acid

503

[1222] TLC: Rf 0.40 (chloroform:methanol=10:1);

[1223] MS: (APCI, Neg.): 390 (M−H)−;

[1224] NMR (CDCl3): δ 7.72-7.67 (m, 2H), 7.05-6.92 (m, 5H), 6.48 (s, 1H), 5.56-5.40 (m, 2H), 4.04 (t, J=6.6 Hz, 2H), 3.85 (s, 2H), 2.44 (d, J=0.9 Hz, 3H), 2.22-2.14 (m, 2H), 1.92-1.83 (m, 2H), 1.67-1.65 (m, 3H).

Example 7(189)

[1225] 1-(4-((3E)-3-Hexen-1-yloxy)benzoyl)-2-methylindole-4-acetic Acid

504

[1226] TLC: Rf 0.38 (chloroform:methanol=10:1);

[1227] MS: (APCI, Neg.): 390 (M−H)−;

[1228] NMR (CDCl3): δ 7.72-7.68 (m, 2H), 7.06-6.93 (m, 5H), 6.48 (s, 1H), 5.64 (dt, J=15.3, 6.0 Hz, 1H), 5.48 (dt, J=15.3, 6.6 Hz, 1H), 4.05 (t, J=6.9 Hz, 2H), 3.86 (s, 2H), 2.52 (dt, J=6.6, 6.9 Hz, 2H), 2.44 (d, J=0.9 Hz, 3H), 2.05 (dq, J=6.0, 7.5 Hz, 2H), 0.99 (t, J=7.5 Hz, 3H).

Example 7(190)

[1229] 1-(4-(3-(N-Methyl-N-phenylamino)propyloxybenzoyl)-5-methylindole-4-acetic Acid

505

[1230] TLC: Rf 0.44 (chloroform:methanol=9:1):

[1231] MS: (APCI, Neg.): 455 (M−H)−;

[1232] NMR (CDCl3): δ 7.71 (d, J=9.0 Hz, 2H), 7.26-7.16 (m, 2H), 7.08-6.92 (m, 5H), 6.79-6.66 (m, 3H), 6.49 (s, 1H), 4.09 (t, J=5.7 Hz, 2H), 3.87 (s, 2H), 3.57 (t, J=6.9 Hz, 2H), 2.60 (s, 3H), 2.45 (s, 3H), 2.20-2.00 (m, 2H).

Example 7(191)

[1233] 1-(4-(4-Methanesulfonyl-3,4-dihydro-2H-1,4-benzoxazin-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

506

[1234] TLC: Rf 0.50 (chloroform:methanol=10:1);

[1235] MS: (APCI, Neg.): 533 (M−H)−;

[1236] NMR (CDCl3): δ 7.72 (m, 3H), 7.12-6.91 (m, 8H), 6.50 (s, 1H), 4.56 (brs, 1H), 4.46-4.26 (m, 3H), 3.88 (s, 2H), 3.57 (dd, J=13.8, 9.3 Hz, 1H), 3.02 (s, 3H) 2.45 (s, 3H).

Example 7(192)

[1237] 1-(4-(4-Methyl-7-methoxy-3,4-dihydro-2H-1,4-benzoxazin-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

507

[1238] TLC: Rf 0.40 (chloroform:methanol=10:1);

[1239] MS: (APCI, Neg.): 499 (M−H)−;

[1240] NMR (CDCl3): δ 7.75-7.62 (m, 4H), 7.04-6.90 (m, 4H), 6.66 (d, J=9.0 Hz, 1H), 6.49 (s, 1H), 6.48 (d, J=9.0 Hz, 1H), 4.70 (m, 1H), 4.30 (dd, J=12.0, 5.4 Hz, 1H), 4.24 (m, 1H), 3.87 (s, 2H), 3.74 (s, 3H), 3.33 (dd, J=11.4, 2.7 Hz, 1H), 3.18 (dd, J=11.7, 6.6, 1H), 2.86 (s, 3H), 2.45 (s, 3H).

Example 7(193)

[1241] 1-(4-(2,2-Dimethyl-1,3-dioxolan-4-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

508

[1242] TLC: Rf 0.38 (chloroform:methanol=10:1);

[1243] NMR (FAB, Pos.): 424 (M+H)+;

[1244] NMR (CDCl3): δ 7.73-7.68 (m, 2H), 7.06-6.92 (m, 5H), 6.48 (s, 1H), 4.52 (m, 1H), 4.20 (dd, J=8.4, 6.6 Hz, 1H), 4.13 (dd, J=9.6, 5.7 Hz, 1H), 4.04 (dd, J=9.6, 5.7 Hz, 1H), 3.94 (dd, J=8.4, 5.7 Hz, 1H), 3.86 (s, 2H), 2.44 (s, 3H), 1.48 (s, 3H), 1.42 (s, 3H).

Example 7(194)

[1245] 1-(4-(6-Fluoro-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

509

[1246] TLC: Rf 0.50 (chloroform:methanol=10:1);

[1247] MS: (APCI, Pos.): 489 (M+H)+;

[1248] NMR (CDCl3): δ 7.72 (d, J=8.7 Hz, 2H), 7.08-6.90 (m, 5H), 6.74 (dd, J=8.7, 5.4 Hz, 1H), 6.50 (s, 1H), 6.35 (m, 2H), 4.60 (m, 1H), 4.30 (dd, J=9.9, 5.1 Hz, 1H), 4.19 (dd, J=9.9, 6.3 Hz, 1H), 3.87 (s, 2H), 3.41 (dd, J=11.7, 3.6 Hz, 1H), 3.30 (dd, J=11.7, 6.6 Hz, 1H), 2.91 (s, 3H), 2.45 (s, 3H).

Example 7(195)

[1249] 1-(4-(4,5-Dimethyl-1,3-dioxolan-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

510

[1250] TLC: Rf 0.35 (chloroform:methanol=10:1);

[1251] MS: (EI, Pos.): 423 (M)+;

[1252] NMR (CDCl3): δ 7.72-7.67 (m, 2H), 7.05-6.90 (m, 5H), 6.48 (s, 1H), 5.54 and 5.44 and 5.27 (each t, J=4.2 Hz, total 1H), 4.36-4.31 and 4.28-4.23 and 3.74-3.69 (each m, total 2H), 4.14 and 4.09 and 4.03 (each d, J=4.2 Hz, total 2H), 3.85 (s, 2H), 2.44 (d, J=0.6 Hz, 3H), 1.38-1.17 (m, 6H).

Example 7(196)

[1253] 1-(4-((3Z)-3-Penten-1-yloxy)benzoyl)-2-methylindole-4-acetic Acid

511

[1254] TLC: Rf 0.51 (chloroform:methanol=10:1);

[1255] MS: (APCI, Neg.):376 (M−H)−;

[1256] NMR (CDCl3): δ 7.69 (m, 2H), 7.08-6.93 (m, 5H), 6.49 (d, J=1.2 Hz, 1H), 5.64-5.40 (m, 2H), 4.06 (t, J=7.0 Hz, 2H), 3.86 (s, 2H), 2.60 (m, 2H), 2.44 (d, J=1.2 Hz, 3H), 1.70 (m, 3H).

Example 7(197)

[1257] 1-(4-(1,3-Benzoxathiolan-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

512

[1258] TLC: Rf 0.51 (chloroform:methanol=10:1);

[1259] MS: (APCI, Neg.): 458 (M−H)−;

[1260] NMR (CDCl3): δ 7.70 (m, 2H), 7.25-7.20 (m, 2H), 7.19-7.10 (m, 1H), 7.08-6.82 (m, 6H), 6.48 (s, 1H), 6.36 (dd, J=6.9, 4.5 Hz, ⅕H), 6.13 (dd, J=4.2, 2.1 Hz, ⅘H), 4.45 (dd, J=10.5, 6.9 Hz, ⅕H), 4.17 (dd, J=10.5, 4.5 Hz, ⅕H), 3.84 (s, 2H), 3.34 (dd, J=13.2, 2.1 Hz, ⅘H), 3.23 (dd, J=13.2, 4.2 Hz, ⅘H), 2.43 (s, 3H).

Example 7(198)

[1261] 1-(4-(1,4-Benzodioxan-5-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

513

[1262] TLC: Rf 0.50 (chloroform:methanol=10:1);

[1263] MS: (APCI, Pos.): 471 (M+H)+;

[1264] NMR (CDCl3): δ 7.69 (d, J=8.7 Hz, 2H), 7.10-6.90 (m, 5H), 6.80 (s, J=8.7, 3H), 6.48 (s, 1H), 4.34-4.18 (m, 6H), 3.86 (s, 2H), 3.12 (t, J=7.2 Hz, 2H), 2.44 (s, 3H).

Example 7(199)

[1265] 1-(4-(1,4-Benzoxathian-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

514

[1266] TLC: Rf 0.25 (chloroform:methanol=10:1);

[1267] MS: (FAB, Pos.): 474 (M+H)+;

[1268] NMR (CDCl3): δ 7.73 (d, J=8.7 Hz, 2H), 7.12-6.83 (m, 9H), 6.49 (s, 1H), 4.68 (m, 1H), 4.37 (dd, J=9.6, 4.8 Hz, 1H), 4.26 (dd, J=9.6, 6.3 Hz, 1H), 3.86 (s, 2H), 3.26-3.15 (m, 2H), 2.45 (s, 3H).

Example 7(200)

[1269] 1-(4-(1,4-Benzoxathian-S, S-dioxide-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

515

[1270] TLC: Rf 0.15 (chloroform:methanol=10:1);

[1271] MS: (FAB, Pos.): 506 (M+H)+;

[1272] NMR (CDCl3): δ 7.88-7.60 (m, 4H), 7.60-7.40 (m, 3H), 7.23-7.10 (m, 1H), 7.10-6.85. (m, 3H), 6.50 (s, 1H), 5.25 (m, 1H), 4.48 (dd, J=10.2, 4.2 Hz, 1H), 4.40 (dd, J=10.2, 4.2 Hz, 1H), 3.86 (s, 2H), 3.76 (dd, J=13.8, 12.0 Hz, 1H), 3.58 (dd, J=13.8, 1.5 Hz, 1H), 2.45 (s, 3H).

Example 7(201)

[1273] 1-(4-(Pyrazin-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

516

[1274] TLC: Rf 0.50 (chloroform:methanol=9:1);

[1275] MS: (APCI, Neg.): 400 (M−H)−;

[1276] NMR (CDCl3): δ 8.86 (s, 1H), 8.65-8.55 (m, 2H), 7.74 (d, J=8.7 Hz, 2H), 7.13-6.90 (m, 5H), 6.50 (s, 1H), 5.33 (s, 2H), 3.87 (s, 2H), 2.45 (s, 3H).

Example 7(202)

[1277] 1-(4-(2,3-Dihydro-1-ethylindol-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

517

[1278] TLC: Rf 0.45 (chloroform:methanol=9:1);

[1279] MS: (APCI, Neg.): 467 (M−H)−;

[1280] NMR (CDCl3): δ 7.76-7.68 (m, 2H), 7.16-6.44 (m, 10H), 5.00-2.80 (m, 7H), 3.87 (s, 2H), 2.45 (s, 3H), 1.20-1.10 (m, 3H).

Example 7(203)

[1281] 1-(4-(2,3,4,5-Tetrahydrofuran-3-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

518

[1282] TLC: Rf 0.33 (chloroform:methanol=9:1);

[1283] MS: (MALDI, Pos.): 393 (M+H)+, 416 (M+Na)+;

[1284] NMR (CDCl3): δ 7.71 (d, J=8.7 Hz, 2H), 7.08-6.98 (m, 3H), 6.95 (d, J=8.7 Hz, 2H), 6.49 (s, 1H), 4.05-3.70(m, 8H), 2.85-2.72 (m, 1H), 2.44 (s, 3H), 2.22-2.08 (m, 1H), 1.82-1.70 (m, 1H).

Example 7(204)

[1285] 1-(4-(2-(2-Phenyl-5-methyloxazol-4-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

519

[1286] TLC: Rf 0.47 (chloroform:methanol=9:1);

[1287] MS: (FAB, Pos.): 495 (M+H)+.

Example 7(205)

[1288] 1-(4-(2-(2,3-Dimethoxyphenyl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

520

[1289] TLC: Rf 0.5 (chloroform:methanol=10:1);

[1290] MS: (APCI, Pos.): 474 (M+H)+;

[1291] NMR (CDCl3): δ 7.69 (d, J=9.0 Hz, 2H), 7.08-6.92 (m, 6H), 6.86 (m, 2H), 6.48 (s, 1H), 4.25 (t, J=7.5 Hz, 2H), 3.88 (s, 6H), 3.84(s, 2H), 3.15 (t, J=7.5 Hz, 2H), 2.44 (s, 3H).

Example 7(206)

[1292] 1-(4-(4-Methyl-6-trifluoromethylbenzoxazin-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

521

[1293] TLC: Rf 0.5 (chloroform:methanol=10:1);

[1294] MS: (APCI, Pos.): 539 (M+H)+;

[1295] NMR (CDCl3): δ 7.73 (d, J=9.0 Hz, 2H), 7.06-6.86 (m, 8H), 6.50 (s, 1H), 4.70 (m, 1H), 4.31 (dd, J=9.9, 4.8 Hz, 1H), 4.21 (dd, J=9.9, 6.3 Hz, 1H), 3.87 (s, 2H), 3.45 (dd, J=11.7, 2.7 Hz, 1H), 3.33 (dd, J=11.7, 6.6 Hz, 1H), 2.96 (s, 3H), 2.45 (s, 3H).

Example 7(207)

[1296] 1-(4-(2-(1,2,3,4-Tetrahydronaphthalen-5-yl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

522

[1297] TLC: Rf 0.4 (chloroform:methanol=10:1);

[1298] MS: (APCI, Pos.): 468 (M+H)+;

[1299] NMR (CDCl3): δ 7.69 (d, J=9.0 Hz, 2H), 7.10-6.92 (m, 8H), 6.49 (s, 1H), 4.22 (t, J=7.5 Hz, 2H), 3.86 (s, 2H), 3.12 (t, J=7.5 Hz, 2H), 2.79 (m, 4H), 2.44 (s, 3H), 1.89-1.77 (m, 4H).

Example 7(208)

[1300] 1-(4-(Quinoxalin-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

523

[1301] TLC: Rf 0.38 (chloroform:methanol=9:1);

[1302] MS: (APCI, Neg.): 450 (M−H)−;

[1303] NMR (CDCl3): δ 9.12 (s, 1H), 8.20-8.08 (m, 2H), 7.88-7.78 (m, 2H), 7.75 (d, J=9.0 Hz, 2H), 7.13 (d, J=9.0 Hz, 2H), 7.10-6.90 (m, 3H), 6.50 (s, 1H), 5.51 (s, 2H), 3.88 (s, 2H), 2.45 (s, 3H).

Example 7(209)

[1304] 1-(4-(6-Chloro-4-methylbenzoxazin-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

524

[1305] TLC: Rf 0.38 (chloroform:methanol=9:1);

[1306] MS: (APCI, Neg.): 503 (M−H)−;

[1307] NMR (CDCl3): δ 7.72 (d J=9.0 Hz, 2H), 7.08-6.90 (m, 5H), 6.74 (dd, J=7.8, 0.9 Hz, 1H), 6.68-6.60 (m, 2H), 6.49 (t, J=0.9 Hz, 1H), 4.68-4.56 (m, 1H), 4.29 (dd, J=9.9, 4.8 Hz, 1H), 4.19 (dd, J=9.9, 6.0 Hz, 1H), 3.87 (s, 2H), 3.41 (dd, J=11.7, 2.7 Hz, 1H), 3.29 (dd, J=11.7, 6.6 Hz, 1H), 2.91 (s, 3H), 2.45 (s, 3H).

Example 7(210)

[1308] 1-(4-(2-(6,6-Dimethyl[3.1.1]bicyclohept-2-enyl)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

525

[1309] TLC: Rf 0.52 (chloroform:methanol=10:1);

[1310] MS: (APCI, Neg.): 456 (M−H)−.

Example 7(211)

[1311] 1-(4-([2.2.1]Bicycloheptan-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

526

[1312] TLC: Rf 0.52 (chloroform:methanol=10:1);

[1313] MS: (APCI, Neg.): 416 (M−H)−.

Example 7(212)

[1314] 1-(4-(Oxetan-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

527

[1315] TLC: Rf 0.52 (chloroform:methanol=10:1);

[1316] MS: (APCI, Neg.): 378 (M−H)−.

Example 7(213)

[1317] 1-(4-(4-Methylpyrazino[2,3-b]oxazin-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

528

[1318] TLC: Rf 0.34 (chloroform:methanol=10:1)

[1319] MS: (FAB, Pos.): 473 (M+H)+;

[1320] NMR (CDCl3): δ 7.75-7.71 (m, 3H), 7.43 (d, J=3.3 Hz, 1H), 7.07-6.92 (m, 5H), 6.50 (s, 1H), 4.80 (m, 1H), 4.40 (dd, J=9.9, 4.5 Hz, 1H), 4.26 (dd, J=9.9, 6.6 Hz, 1H), 3.87 (s, 2H), 3.65 (dd, J=12.3, 3.3 Hz, 1H), 3.59 (dd, J=12.3, 6.9 Hz, 1H), 3.17 (s, 3H), 2.45 (d, J=0.9 Hz, 3H).

Example 7(214)

[1321] 1-(4-(Tetrahydropyran-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

529

[1322] TLC: Rf 0.44 (chloroform:methanol=9:1);

[1323] MS: (FAB, Pos.): 407 (M+H)+.

Example 7(215)

[1324] 1-(4-(2-(N-(2-Cyanoethyl)-N-phenylamino)ethyloxy)benzoyl)-2-methylindole-4-acetic Acid

530

[1325] TLC: Rf 0.40 (chloroform:methanol=9:1);

[1326] MS: (FAB, Glycerin+m-NBA): 482 (M+H)+.

Example 7(216)

[1327] 1-(4-(1,4-Dimethyl-1,2,3,4-tetrahydroquinoxalin-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

531

[1328] TLC: Rf 0.48 (chloroform:methanol=9:1);

[1329] MS: (APCI, Neg.): 482 (M−H)−;

[1330] NMR (CDCl3): δ 7.70 (d, J=9.0 Hz, 2H), 7.08-6.92 (m, 5H), 6.80-6.66 (m, 2H), 6.62-6.48 (m, 3H), 4.27-4.07 (m, 2H), 3.87 (s, 2H), 3.83-3.73 (m, 1H), 3.36-3.20 (m, 2H), 3.05 (s, 3H), 2.88 (s, 3H), 2.45 (s, 3H).

Example 7(217)

[1331] 1-(4-(5-Fluoro-4-methyl-3,4-dihydro-2H-benzoxazin-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

532

[1332] TLC: Rf 0.47 (chloroform:methanol=9:1);

[1333] MS: (Pos.): 488 (M)+;

[1334] NMR (CDCl3): δ 7.72 (d, J=9.0 Hz, 2H), 7.08-6.90 (m, 5H), 6.83-6.73 (m, 1H), 6.58-6.45 (m, 3H), 4.76-4.66 (m, 1H), 4.37 (dd, J=9.9, 5.1 HZ, 1H), 4.24 (dd, J=9.9, 6.6 Hz, 1H), 3.87 (s, 2H), 3.46 (dd, J=12.0, 2.7 Hz, 1H), 3.34 (dd, J=12.0, 6.6 Hz, 1H), 2.94 (s, 3H), 2.45 (s, 3H).

Example 7(218)

[1335] 1-(4-(4,8-Dimethyl-3,4-dihydro-2H-benzoxazin-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

533

[1336] TLC: Rf 0.48 (chloroform:methanol=9:1);

[1337] MS: (Neg.): 483 (M−H)−;

[1338] NMR (CDCl3): δ 7.76-7.66 (m, 2H), 7.08-6.90 (m, 6H), 6.82-6.74 (m, 1H), 6.58 (d, J=7.5 Hz, 1H), 6.49 (s, 1H), 4.74-4.64 (m, 1H), 4.33 (dd, J=9.9, 5.4 Hz, 1H), 4.23 (dd, J=9.9, 6.3 Hz, 1H), 3.87 (s, 2H), 3.41 (dd, J=11.4, 2.7 Hz, 1H), 3.26 (dd, J=11.4, 6.3 Hz, 1H), 2.91 (s, 3H), 2.45 (s, 3H), 2.18 (s, 3H).

Example 7(219)

[1339] 1-(4-(4-Methyl-3,4-dihydro-2H-benzothiazin-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

534

[1340] TLC: Rf 0.48 (chloroform:methanol=10:1);

[1341] MS: (APCI, Neg.): 485 (M−H)−;

[1342] NMR (CDCl3): δ 7.68 (d, J=8.7 Hz, 2H), 7.22-6.92 (m, 7H), 6.70-6.65 (m, 2H), 6.47 (s, 1H), 4.27 (dd, J=9.6, 9.3 Hz, 1H), 4.16 (dd, J=9.3, 5.1 Hz, 1H), 3.83 (s, 2H), 3.67 (m,1H), 3.57 (m, 2H), 2.91 (s, 3H), 2.42 (s, 3H).

Example 7(220)

[1343] 1-(4-(4-Methyl-3,4-dihydro-2H-pyrido[3,2-b]oxazin-2-ymethyloxy)benzoyl)-2-methylindole-4-acetic Acid

535

[1344] TLC: Rf 0.35 (chloroform:methanol=9:1);

[1345] MS: (FAB, Pos.): 472 (M+H)+;

[1346] NMR (CDCl3): δ 7.81 (dd, J=5.1, 1.8 Hz, 1H), 7.73 (d, J=8.7 Hz, 2H), 7.10-6.90 (m, 6H), 6.56 (dd, J=7.8, 5.1 Hz, 1H), 6.50 (s, 1H), 4.67-4.58 (m, 1H), 4.31 (dd, J=9.9, 5.1 HZ, 1H), 4.20 (dd, J=9.9, 6.0 Hz, 1H), 3.87 (s, 2H), 3.58 (dd, J=12.0, 3.0 Hz, 1H), 3.49 (dd, J=12.0, 6.9 Hz, 1H), 3.15 (s, 3H), 2.45 (s, 3H).

Example 7(221)

[1347] 1-(4-(4-Methyl-3,4-dihydro-2H-pyrido[2,3-b]oxazin-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

536

[1348] TLC: Rf 0.40 (chloroform:methanol=10:1);

[1349] MS: (FAB, Pos.): 472 (M+H)+;

[1350] NMR (CDCl3): δ 7.74-7.69 (m, 2H), 7.67 (dd, J=5.1, 1.5 Hz, 1H), 7.05-6.85 (m, 7H), 6.51 (s, 1H), 4.82 (m, 1H), 4.37 (dd, J=9.6, 4.2 Hz, 1H), 4.23 (dd, J=9.6, 6.9 Hz, 1H), 3.87 (s, 2H), 3.45 (dd, J=12.0, 3.3 Hz, 1H), 3.31 (dd, J=12.0, 7.0 Hz, 1H), 2.92 (s, 3H), 2.44 (d, J=0.9 Hz, 3H).

Example 7(222)

[1351] 1-(4-(7-Fluoro-4-methyl-3,4-dihydro-2H-benzoxazin-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

537

[1352] TLC: Rf 0.33 (chloroform:methanol=9:1);

[1353] MS: (MARDI, Pos.): 488 (M)+;

[1354] NMR (CDCl3): δ 7.77-7.61 (m, 2H), 7.59-7.41 (m, 2H), 7.08-6.90 (m, 4H), 6.60 (d, J=8.1 Hz, 2H), 6.50 (s, 1H), 4.75-4.65 (m, 1H), 4.34-4.18 (m, 2H), 3.86 (s, 2H), 3.40-3.18 (m, 2H), 2.87 (s, 3H), 2.44 (s, 3H).

Example 7(223)

[1355] 1-(4-(7-Cyano-4-methyl-3,4-dihydro-2H-benzoxazin-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

538

[1356] TLC: Rf 0.31 (chloroform:methanol=9:1);

[1357] MS: (APCI, Pos.): 495 (M)+, 518 (M+Na)+;

[1358] NMR (CDCl3): δ 7.72 (d, J=8.7 Hz, 2H), 7.09-6.82 (m, 8H), 6.50 (s, 1H), 4.78-4.67 (m, 1H), 4.35-4.18 (m, 2H), 3.87 (s, 2H), 3.49-3.30 (m, 2H), 2.95 (s, 3H), 2.45 (s, 3H).

Example 7(224)

[1359] 1-(4-(4-Methyl-6-methoxy-3,4-dihydro-2H-benzoxazin-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

539

[1360] TLC: Rf 0.40 (chloroform:methanol=10:1);

[1361] MS: (APCI, Pos.): 501 (M+H)+;

[1362] NMR (CDCl3): δ 7.72 (d, J=8.7 Hz, 2H), 7.08-6.90 (m, 5H), 6.75 (d, J=8.7 Hz, 1H), 6.49 (s, 1H), 6.29 (d, J=2.7 Hz, 1H), 6.23 (dd, J=8.7, 2.7 Hz, 1H), 4.61 (m, 1H), 4.30 (dd, J=9.9, 4.8 Hz, 1H), 4.18 (m, 1H), 3.87 (s, 2H), 3.76 (s, 3H), 3.40 (dd, J=11.4, 9.0 Hz, 1H), 3.28 (dd, J=11.4, 6.6 Hz, 1H), 2.91 (s, 3H), 2.44 (s, 3H).

Example 7(225)

[1363] 1-(4-(1-Methylindolin-3-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

540

[1364] TLC: Rf 0.47 (chloroform:methanol=9:1);

[1365] MS: (APCI, Neg.): 453 (M−H)−;

[1366] NMR (CDCl3): δ 7.74-7.68 (m, 3H), 7.22-7.10 (m, 2H), 7.08-6.90 (m, 4H), 6.72 (t, J=6.6 Hz, 1H), 6.53 (d, J=8.1 Hz, 1H), 6.49 (s, 1H), 4.24-4.06 (m, 2H), 3.87 (s, 2H), 3.78-3.70 (m, 1H), 3.49 (t, J=8.1 Hz, 1H), 3.38 (dd, J=9.0, 5.1 Hz, 1H), 2.79 (s, 3H), 2.45 (s, 3H).

Example 7(226)

[1367] 1-(4-(4-Methyl-3,4-dihydro-2H-benzoxazin-2-yl)carbonylamino)benzoyl)-2-methylindole-4-acetic Acid

541

[1368] TLC: 0.48 (chloroform:methanol=10:1);

[1369] MS: (APCI, Neg.): 482 (M−H)−;

[1370] NMR (CDCl3): δ 8.53 (s, 1H), 7.72 (s, 4H), 7.20-6.90 (m, 5H), 6.80-6.70 (m, 2H), 6.49 (s, 1H), 4.89 (dd, J=6.9, 3.3 Hz, 1H), 3.85 (s, 2H), 3.57 (dd, J=12.0, 3.3 Hz, 1H), 3.44 (dd, J=12.0, 6.9 Hz, 1H), 2.92 (s, 3H), 2.49 (s, 3H).

Example 7(227)

[1371] 1-(4-N-Methyl-N-(4-methyl-3,4-dihydro-2H-benzoxazin-2-ylcarbonyl)amino)benzoyl)-2-methylindole-4-acetic Acid

542

[1372] TLC: Rf 0.48 (chloroform:methanol=10:1);

[1373] NMR (CDCl3): δ 7.77 (d, J=8.7 Hz, 2H), 7.43 (d, J=8.7 Hz, 2H), 7.05 (d, J=6.3 Hz, 1H), 6.90-6.75 (m, 3H), 6.70-6.55 (m, 3H), 6.49 (s, 1H), 4.77 (brd, J=6.3 Hz, 1H), 3.84 (s, 2H), 3.53 (dd, J=12.0, 7.8 Hz, 1H), 3.40 (s, 3H), 3.30 (dd, J=12.0, 2.4 Hz, 1H), 2.86 (s, 3H), 2.41 (s, 3H).

Example 7(228)

[1374] 1-(4-(5-Methyl-2,3,4,5-tetrahydrofuran-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid

543

[1375] TLC: Rf 0.52 (chloroform methanol=10:1);

[1376] NMR (CDCl3): δ 7.69 (d, J=9.3 Hz, 2H), 7.07-6.88 (m, 5H), 6.48 (s, 1H), 4.50-4.30 (m, 1H), 4.17-3.95 (m, 2H), 3.85 (s, 2H), 3.42 (dd, J=16.5, 8.1 Hz, 1H), 2.50-2.20 (m) and 2.44 (s) total 5H, 2.09-1.94 (m) and 1.79-1.67 (m) total 1H, 1.50-1.22 (m, 1H), 1.15-1.05 (m, 3H).

[1377] In addition, the compound prepared in Example 7(224) may be prepared by following procedures as a series of reactions of Reference Example 22→Reference Example 23→Reference Example 24→Reference Example 25→Reference Example 26→Reference Example 27→Reference Example 28→Example 8.

REFERENCE EXAMPLE 22

[1378] 2-Ethoxycarbonyl-6-methoxy-3,4-dihydro-2H-benzoxazine

544

[1379] To a solution of 2-amino-4-methoxyphenol (5.5 g) in acetone (200 ml) was added potassium carbonate (5 g), and the mixture was stirred at 40° C. under an atmosphere of argon. To the mixture was added dropwise ethyl 1,2-dibromopropionate and potassium carbonate (15 g), and the mixture was refluxed for 15 hours. After cooling to room temperature, the mixture was filtered. The filtrate was poured into water and then extracted with ethyl acetate (3 times). The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatoqraphy on silica qel (n-hexane:ethyl acetate=10:1) to qive the title compound (1.65 g) having the following physical data.

[1380] TLC: Rf 0.44 (n-hexane:ethyl acetate=2:1).

REFERENCE EXAMPLE 23

[1381] 2-Hydroxymethyl-6-methoxy-3,4-dihydro-2H-benzoxazine

545

[1382] To a solution of lithium aluminum hydride (560 mg) in tetrahydrofuran (50 ml) was added dropwise a solution of the compound prepared in above-mentioned Reference Example (1.65 g) in tetrahydrofuran (30 ml) under an atmosphere of argon, and the mixture was stirred for 15 minutes. To the reaction mixture was added a saturated aqueous solution of sodium chloride, and the mixture was extracted with ethyl acetate (3 times). The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane:ethyl acetate=4:1) to give the title compound (1.3 g) having the following physical data.

[1383] TLC: Rf 0.17(n-hexane:ethyl acetate=2:1).

REFERENCE EXAMPLE 24

[1384] 2-Hydroxymethyl-6-methoxy-4-methyl-3,4-dihydro-2H-benzoxazine

546

[1385] To a solution of the compound (1.3 g) prepared in above-mentioned Reference Example in acetone (50 ml)—N,N-dimethylformamide (10 ml) was added potassium carbonate (10 g) and methyl iodide (3 ml), and the mixture was stirred at 58° C. for 2 hours. To the mixture was added methyl iodide (3 ml) and the mixture was stirred for 12 hours. The reaction mixture was poured into water and then extracted with ethyl acetate (3 times). The organic layer was washed with a saturated aqueous solution of sodium chloride and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane:ethyl acetate=2:1) to give the title compound (140 mg) having the following physical data.

[1386] TLC: Rf 0.25(n-hexane ethyl acetate=2:1).

REFERENCE EXAMPLE 25

[1387] 2-Methylindole-4-acetic Acid Benzyl Ester

547

[1388] To a solution of the compound (55.0 g) prepared in Reference Example 5 in N,N-dimethylformamide (500 ml) was added potassium carbonate (109 g) with vigorously stirring under an atmosphere of argon. To the mixture was added benzyl bromide (34.6 ml) and the mixture was stirred at room temperature for 2 hours. The reaction solution was poured into water (2000 ml) and extracted with toluene. The organic layer was washed with a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride, successively, dried over anhydrous magnesium sulfate and filtrated. The filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane:ethyl acetate=5:1) to give the title compound (70.3 g) having the following physical data.

[1389] TLC: Rf 0.85(n-hexane:ethyl acetate=1:1).

REFERENCE EXAMPLE 26

[1390] 1-(4-Acetoxybenzoyl)-2-methylindole-4-acetic Acid Benzyl Ester

548

[1391] A mixture of 4-acetoxybenzoic acid (516 mg) and oxalyl chloride (0.5 ml) was stirred for 30 minutes. The mixture was concentrated under reduced pressure to give 4-acetoxybenzoyl chloride.

[1392] To a solution of the compound (400 mg) prepared in Reference Example 25 in methylene chloride (7 ml) was added sodium hydroxide (286 mg) and tetrabutylammonium chloride (20 mg) at room temperature. The mixture was added the above-mentioned solution of 4-acetoxybenzoyl chloride in methylene chloride (3 ml), and the mixture was stirred at room temperature overnight. The reaction mixture was filtrated, and the filtrate was concentrated. The residue was purified by column chromatography on silica gel (n-hexane:ethyl acetate=7:3) to give the title compound (500 mg) having the following physical data.

[1393] TLC: Rf 0.34(n-hexane:ethyl acetate=7:3);

[1394] NMR (CDCl3): δ 7.76 (d, J=8.7 Hz, 2H), 7.40-7.20 (m, 7H), 7.08-6.92 (m, 3H), 6.47 (s, 1H), 5.15 (s, 2H), 3.88 (s, 2H), 2.40 (s, 3H), 2.35 (s, 3H).

REFERENCE EXAMPLE 27

[1395] 1-(4-Hydroxybenzoyl)-2-methylindole-4-acetic Acid Benzyl Ester

549

[1396] The compound (500 mg) prepared in Reference Example 26 was dissolved in 5% piperidine/methylene chloride (5 ml), and the mixture was stirred for 1 hours. The reaction mixture was concentrated and the residue was purified by column chromatography on silica gel (chloroform:methanol=19:1) to give the title compound (450 mg) having the following physical data.

[1397] TLC: Rf 0.61 (chloroform:methanol=9:1);

[1398] NMR (CDCl3): δ 7.72 (m, 2H), 7.44-7.26 (m, 5H), 7.08-6.84 (m, 5H), 6.45 (s, 1H), 5.83 (brs, 1H), 5.15 (s, 2H), 3.88 (s, 2H), 2.42 (s, 3H).

REFERENCE EXAMPLE 28

[1399] 1-(4-(6-Methoxy-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-2-ylmethyloxy)benzoyl)-2-methylindole-4-acetic Acid Benzyl Ester

550

[1400] To a solution of the compound (60 mg) prepared in Reference Example 24 in methylene chloride (10 ml) was added triphenylphosphine (76 mg), the compound (95 mg) prepared in Reference Example 27 and diethyl azodicarboxylate (126 mg), successively, and the mixture was stirred for 3 hours. The mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane:ethyl acetate=4:1) to give the compound (85 mg) of the present invention having the following physical data.

[1401] TLC: Rf 0.57(n-hexane:ethyl acetate=1:1);

[1402] NMR (CDCl3): 7.71 (d, J=9.0 Hz, 2H), 7.32 (m, 5H), 7.08-6.90(m, 5H), 6.75 (d, J=8.4 Hz, 1H), 6.46 (s, 1H), 6.28 (d, J=2.7 Hz, 1H), 6.23 (dd, J=8.7, 2.7 Hz, 1H), 5.15 (s, 2H), 4.60 (m, 1H), 4.27 (dd, J=9.9, 6.6 Hz, 1H), 4.18 (dd, J=9.9, 6.3 Hz, 1H), 3.88 (s, 2H), 3.76 (s, 3H), 3.39 (dd, J=11.7, 2.7 Hz, 1H), 3.27 (dd, J=11.7, 6.6 Hz, 1H), 2.90 (s, 3H), 2.42 (s, 3H).

EXAMPLE 8 (the same compound as Example 7(224))

[1403] 1-(4-(6-Methoxy-4-methyl-3,4-dihydro-2H-1,4-benzoxazin-2-ylmethyloxy)benzoyl)-2-methylindol-4-ylacetic Acid

551

[1404] The compound (50 mg) prepared in above-mentioned example, ethyl acetate (5 ml) and palladium hydroxide (100 mg) were mixed. The mixture was stirred for 2 hours under an atmosphere of argon. The reaction mixture was filtrated and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (chloroform methanol=10:1) to give the compound of the present invention having the following physical data.

[1405] TLC: Rf 0.40 (chloroform:methanol=10:1);

[1406] MS: (APCI, Pos.): 501 (M+H)+;

[1407] NMR (CDCl3): δ 7.72 (d, J=8.7 Hz, 2H), 7.08-6.90 (m, 5H), 6.75 (d, J=8.7 Hz, 1H), 6.49 (s, 1H), 6.29 (d, J=2.7 Hz, 1H), 6.23 (dd, J=8.7, 2.7 Hz, 1H), 4.61 (m, 1H), 4.30 (dd, J=9.9, 4.8 Hz, 1H), 4.18 (m, 1H), 3.87 (s, 2H), 3.76 (s, 3H), 3.40 (dd, J=11.4, 9.0 Hz, 1H), 3.28 (dd, J=11.4, 6.6 Hz, 1H), 2.91 (s, 3H), 2.44 (s, 3H).

[1408] In addition to the compound of Example 7(224), the compounds of Example 1 to Example 1(75), Example 7 to Example 7(223), (225) and (228) may be prepared by the same procedures as a series of reactions of Reference Example 28→Example 8, using corresponding compounds.

[1409] The compounds of Examples 1(8), 1(51), 1(67), 1(68), 1(69), Examples 7(37) and 7(151) may be prepared by protection of hydroxy or amino group by protective group followed by deprotection before the reaction corresponding example 9.

FORMULATION EXAMPLE 1

[1410] The following components were admixed in conventional method and punched out to obtain 100 tablets each containing 5 mg of active ingredient.

81-(4-(2-Propyloxyethoxy)benzoyl)-2-methylindole-4-acetic acid500 mgCarboxymethyl Cellulose calcium200 mgMagnesium stearate100 mgMicrocrystalline cellulose 9.2 g

Number	Date	Country	Kind
2000-064696	Mar 2000	JP
2000-231857	Jul 2000	JP

Indole derivatives, process for preparation of the same and use thereof

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