JP2003500488A - Sulfonamide compounds having pharmacological activity - Google Patents

Abstract

(57) Abstract: The present invention relates to novel sulfonamide compounds having 5-HT ₇ antagonist activity, processes for their preparation, compositions containing them, and to their use in the treatment of CNS and other disorders.

Description

Detailed Description of the Invention

The present invention relates to compounds with pharmacological activity, processes for their preparation, compositions containing them and their use in the treatment of the CNS and other disorders. WO97 / 29097, WO97 / 48681 and WO97 / forty-nine thousand six hundred ninety-five are all a 5-HT ₇ receptor antagonists, discloses a series of sulfonamide derivatives which are said to be useful in the treatment of various CNS disorders.

[0002] A structurally novel class of compounds has now been found, which also possesses 5-HT ₇ receptor activity. Therefore, the present invention, in a first aspect, is of formula (I):

[Chemical 7] (I) ^[wherein, R 1, ^{R 2} and ^{R 3} are independently hydrogen, halogen, _{hydroxy, C 1-6} alkyl or _{C 1-6} alkoxy; m is 1 or 2; X is nitrogen , Carbon or CH; when X is nitrogen or CH

[Chemical 8] Is a single bond; when X is carbon,

[Chemical 9] Is a double bond;   D is a single bond, C = O, O or CH_TwoHowever, when X is nitrogen, D
Is not oxygen;   P is phenyl, naphthyl, or selected from oxygen, nitrogen and sulfur
A 5- or 6-membered heteroaryl ring containing 1 to 3 heteroatoms
, Or containing 1 to 3 heteroatoms selected from oxygen, nitrogen and sulfur.
A benzo-fused heteroaryl ring;   R^FourIs NR⁵R⁶C optionally substituted by_1-6Alkyl, aryl,
Aryl C_1-6Alkyl, C_1-6Alkoxy, C_1-6Alkylthio, shea
No, hydroxy, nitro, halogen, CF_Three, C_TwoF₅, NR⁵R⁶, CONR ⁵ R⁶, NR⁵COR⁶, S (O)_pNR⁵R⁶, CHO, OCF_Three, SCF_Three , COR⁷, CH_TwoOR⁷, CO_TwoR⁷Or OR⁷And   p is 0, 1 or 2, and R⁵, R⁶And R⁷Independently hydrogen, C_1-6 Alkyl, aryl or aryl C_1-6Alkyl;   n means 0, 1, 2 or 3] or a pharmaceutically acceptable compound thereof
Provided salt.

[0003]   C_1-6Alkyl groups, either alone or as part of another group, can be straight-chain or branched.
You can Unless otherwise specified, the term "halogen" used herein is fluorine, chlorine.
, A group selected from bromine or iodine. As used herein, the term "aryl" refers to
Unless otherwise specified, it refers to groups such as phenyl or naphthyl. Such aryl
The group is one or more C_1-6Substituted by alkyl or halogen
May be.   Suitably, the group R¹, R^TwoAnd R^ThreeAre independently hydrogen or fluorine
, Halogen such as chlorine or bromine, or C such as methyl_1-6 It is alkyl. Preferably the group R¹Is the meta position relative to the sulfonamide bond.
Is a chill group, R^TwoAnd R^ThreeAre both hydrogen.   Preferably D is a single bond.   When P is naphthyl, this group is naphthalen-1-yl and naphthale.
Both of them are shown to be a 2-n-yl group. P is a 5- or 6-membered heteroaryl ring
When, suitable examples are thienyl, furyl, pyrrolyl, triazolyl, imine
Dazolyl, oxazolyl, thiazolyl, oxadiazolyl, isothiazolyl, a
Soxazolyl, thiadiazolyl, pyridyl, pyrimidinyl, pyrrolidinyl and
And pyrazinyl. Suitable when P is a benzofused heteroaryl ring.
Examples are indolyl, benzimidazolyl, benzoxazolyl, benzothiazo.
Includes ril, quinolinyl and isoquinolinyl. The above groups are carbon atoms or
Can be attached to the rest of the molecule via the appropriate nitrogen atom, if present.
it can. However, when D is O a heteroaryl or benzofused
The heteroaryl ring must be attached to the rest of the molecule via a carbon atom.
Yes. Preferably P is phenyl, naphthyl, benzimidazol-2-yl, 2
-Oxo-2,3-dihydrobenzimidazol-1-yl, indole-3-
And benzoxazol-2-yl and benzothiazol-2-yl
.   R^FourPreferred examples of groups are halogen such as fluorine or chlorine, NR⁵R⁶By
C such as optionally substituted methyl_1-6Alkyl, hydroxy, CF_Three , Such as methoxy C_1-6Alkoxy or R⁷A group COR in which is methyl ⁷ Or CO_TwoR⁷Is. the group R when n is 2 or more^FourIs the same
You may meet or be different. Preferably, n is 0 or 1.

Particularly preferred compounds of the invention include the following: (R) -2- (1- (1- (toluene-3-sulfonyl) -pyrrolidin-2-ylmethyl) -piperidine-
4-yl) -1H-benzimidazole, (S) -2- (1- (1- (toluene-3-sulfonyl) -pyrrolidin-2-ylmethyl) -piperidine-
4-yl) -1H-benzimidazole, (RS) -2- (1- (1- (toluene-3-sulfonyl) -piperidin-2-ylmethyl) -piperidine
-4-yl) -1H-benzimidazole, (R) -5-fluoro-2- (1- (1- (toluene-3-sulfonyl) -pyrrolidin-2-ylmethyl)-
Piperidin-4-yl) -1H-benzimidazole, (S) -5-fluoro-2- (1- (1- (toluene-3-sulfonyl) -pyrrolidin-2-ylmethyl)-
Piperidin-4-yl) -1H-benzimidazole, (RS) -5-fluoro-2- (1- (1- (toluene-3-sulfonyl) -piperidin-2-ylmethyl)
-Piperidin-4-yl) -1H-benzimidazole, (R) -2- (1- (1- (toluene-3-sulfonyl) -pyrrolidin-2-ylmethyl) -piperidine-
4-yl) -1H-benzoxazole, (S) -2- (1- (1- (toluene-3-sulfonyl) -pyrrolidin-2-ylmethyl) -piperidine-
4-yl) -1H-benzoxazole, (RS) -2- (1- (1- (toluene-3-sulfonyl) -piperidin-2-ylmethyl) -piperidine
-4-yl) -1H-benzoxazole, (R) -2- (4- (1- (toluene-3-sulfonyl) -pyrrolidin-2-ylmethyl) -piperazine-1
-Yl) -1H-benzimidazole, (S) -2- (4- (1- (toluene-3-sulfonyl) -pyrrolidin-2-ylmethyl) -piperazine-1
-Yl) -1H-benzimidazole, (RS) -2- (4- (1- (toluene-3-sulfonyl) -piperidin-2-ylmethyl) -piperazine-
1-yl) -1H-benzimidazole, (R) -1- (2-methoxy-phenyl) -4- (1- (toluene-3-sulfonyl) -pyrrolidin-2-ylmethyl) -piperazine, (S)- 1- (2-methoxy-phenyl) -4- (1- (toluene-3-sulfonyl) -pyrrolidin-2-ylmethyl) -piperazine, (RS) -1- (2-methoxy-phenyl) -4- (1 -(Toluene-3-sulfonyl) -piperidine-2-
(Ilmethyl) -piperazine, (R) -3- (1- (1- (toluene-3-sulfonyl) -pyrrolidin-2-ylmethyl) -piperidine-
4-yl) -1H-indole, (S) -3- (1- (1- (toluene-3-sulfonyl) -pyrrolidin-2-ylmethyl) -piperidine-
4-yl) -1H-indole, (RS) -3- (1- (1- (toluene-3-sulfonyl) -piperidin-2-ylmethyl) -piperidine
-4-yl) -1H-indole or a pharmaceutically acceptable salt thereof.

The compounds of formula (I) are customary pharmaceutically acceptable salts, for example maleic acid, hydrochloric acid, hydrobromic acid, phosphoric acid, acetic acid, fumaric acid, salicylic acid, citric acid, lactic acid, mandelic acid. Acid addition salts can be formed with salts such as, tartaric acid and methanesulfonic acid. The compounds of formula (I) may form solvates such as hydrates and the present invention also includes these forms. As used herein, the term "compound of formula (I)" also includes these forms. Certain compounds of formula (I) may exist as stereoisomers, including diastereomers and enantiomers, and the invention includes these individual stereoisomers as well as mixtures thereof, including racemates. . Different stereoisomers may be separated from each other by conventional methods, or specific isomers may be obtained by stereospecific or asymmetric synthesis. The present invention also includes tautomers and mixtures thereof.

In a further aspect, the present invention also provides a process for the preparation of a compound of formula (I) or a pharmaceutically acceptable salt thereof, said process comprising formula (II):

[Chemical 10] (II) [wherein R ¹ , R ² , R ³ and m are the same as defined in formula (I) and Y represents a leaving group], and a compound represented by formula (III) :

[Chemical 11] (III) [wherein

[Chemical 12] , X, D, P, n and R ⁴ are the same as defined in formula (I)], and then, where appropriate: removing the protecting group: It is characterized in that the obtained salt is obtained.

Suitable leaving groups Y include OSO ₂ Ar groups such as halogen (especially chloro) and tosylate. Preferably, the reaction of compounds of formulas (II) and (III) is carried out in a solvent such as dichloromethane or acetonitrile, optionally in the presence of a base such as sodium iodide and potassium carbonate. One of ordinary skill in the art will recognize that certain groups may need to be protected. Suitable protecting groups and methods for addition and removal are conventional in the field of organic chemistry, for example Greene TW'Protective groups in organic synthesis' New
There are methods described in York, Wiley (1981). Compounds of formula (II) and (III) are described herein, but they are commercially available or can be prepared by known methods or methods analogous to known methods. Pharmaceutically acceptable salts may be conveniently prepared by reaction with the appropriate acid or acid derivative.

The compounds of formula (I) and their pharmaceutically acceptable salts possess 5-HT ₇ receptor antagonist activity and are associated with anxiety, depression, sleep disorders (including disruption of the circadian rhythm), polarization. Some CNS such as headaches, Parkinson's disease, schizophrenia, pain, loss of appetite
Diseases and disorders related to neurodegeneration resulting from inflammation, spastic colon, renal disease, hypotension, cardiovascular shock, ischemic events such as stroke, septic shock and gastrointestinal such as IBS (irritable bowel syndrome) It is considered potentially useful in the treatment or prevention of other conditions such as disease.

Thus, the present invention provides a compound of formula (I) or a compound thereof, which is used as a therapeutic substance, in particular for the treatment or prophylaxis of the abovementioned diseases, in particular for the treatment or prevention of depression and / or sleep disorders. Also provided are pharmaceutically acceptable salts. The present invention further provides a method for treating or preventing the above-mentioned diseases in mammals including humans, which method comprises administering to a subject a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof. It is characterized by doing. In particular, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof for use in the treatment or prevention of depression and / or sleep disorders. The present invention also provides a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or excipient.

Suitably, the pharmaceutical composition of the invention may be prepared by mixing at ambient temperature and atmospheric pressure, usually the pharmaceutical composition of the invention is for oral, parenteral or rectal administration. Suitable, such as tablets, capsules, oral liquid preparations, powders, granules, lozenges, reconstitutable powders, injectable or infusible solutions or suspensions or even in the form of suppositories Good. Orally administrable compositions are generally preferred. Tablets and capsules for oral administration may be in unit dosage form and may contain conventional excipients such as binders, fillers, molding lubricants, disintegrants and acceptable wetting agents. . The tablets may be coated by methods well known in normal pharmaceutical practice. Oral liquid preparations may be, for example, in the form of aqueous or oily suspensions, solutions, emulsions, syrups or elixirs, or in the form of dry products which are reconstituted with water or other suitable carrier before use. It may be. Such liquid preparations contain suspending agents, emulsifying agents, non-aqueous carriers (which may be edible oils), preservatives and, if necessary, conventional additives such as conventional flavors or colors. Good. For parenteral administration, liquid unit dosage forms are prepared utilizing a compound of the invention or a pharmaceutically acceptable salt thereof and a sterile carrier. The compound, depending on the carrier and concentration used, can be either suspended or dissolved in the carrier. In preparing solutions, the compound can be dissolved for injection and sterilized before filling into a suitable vial or ampoule and sealing. Advantageously, adjuvants such as local anesthetics, preservatives and buffers are dissolved in the carrier. To improve stability, the composition can be filled into vials and then frozen and the water removed under reduced pressure. A parenteral suspension is prepared in substantially the same manner, except that the compound is suspended in the carrier without being dissolved and sterilization is not carried out by filtration. The compound can be sterilized by exposure to ethylene oxide before suspension in a sterile carrier. Advantageously, a surfactant or wetting agent is included in the composition to facilitate uniform distribution of the compound. Depending on the method of administration, the composition may be from 0.1% to 99% by weight, preferably 1%.
It may contain from 0% to 60% by weight of active substance. The dose of the compound used in the treatment of the above diseases will vary according to the usual methods, depending on the severity of the disease, the weight of the subject, and other similar factors. However, as a general guide, a suitable unit dose is 0.05 to 1000 mg, more suitably 0.05 to 20.0 mg, eg 0.2 to 5 mg; Many, eg two or three times a day, may be given 1
The total daily dose should be in the range of about 0.5 to 100 mg; such treatment may be continued for many weeks or months. No unacceptable toxicological effects are expected with the compounds of the invention when administered in accordance with the invention. The following Descriptions and Examples illustrate the preparation of compounds of this invention.

Description Example 1 (R) -toluene-3-sulfonic acid 1- (toluene-3-sulfonyl) -pyrrolidin-2-yl methyl ester (D1) diisopropylethylamine (9.6 mL, 49 mmol) and toluene-3 chloride -Sulfonyl (8.3 g, 44 mmol) was added to dichloromethane (100 m).
l) was added to a solution of D-prolinol (2.0 g, 20 mmol). The resulting solution was heated to reflux for 15 hours. After cooling, the solution was added to 100 mL of saturated aqueous sodium bicarbonate solution. The organic phase is separated, dried over sodium sulfate,
It was concentrated under reduced pressure. The residue was purified by silica gel chromatography to give the title compound (1.6 g, 19%). _{1H NMR (250MHz, CDCl 3)} 7.75 (2H, m), 7.59 (2H, m), 7.48 (2H, m), 7.40 (
2H, m), 4.26 (1H, dd, 9.9, 3.4Hz), 4.00 (1H, dd, 9.9, 7.9Hz), 3.77 (1H,
m), 3.40 (1H, m), 3.08 (1H, m), 2.47 (3H, s), 2.43 (3H, s), 1.89 1.55 (
4H, m) .MS m / e 410 (MH ⁺ )

Description Example 2 (S) -Toluene-3-sulfonic acid 1- (toluene-3-sulfonyl) -pyrrolidin-2-ylmethyl ester (D2) Using the method described in Description Example 1, L-prolinol The title compound was prepared from
_{1H NMR (250MHz, CDCl 3)} 7.75 (2H, m), 7.59 (2H, m), 7.48 (2H, m), 7.40 (
2H, m), 4.26 (1H, dd, 9.9, 3.4Hz), 4.00 (1H, dd, 9.9, 7.9Hz), 3.77 (1H,
m), 3.40 (1H, m), 3.08 (1H, m), 2.47 (3H, s), 2.43 (3H, s), 1.89 1.55 (
4H, m) .MS m / e 410 (MH ⁺ )

Description Example 3 (RS) -Toluene-3-sulfonic acid 1- (toluene-3-sulfonyl) -piperidin-2-ylmethyl ester (D3) Using the method described in Description Example 1, piperidine-2- The title compound was prepared from methanol. _{1H NMR (CDCl 3) 7.66 7.63} (4H, m), 7.46 (2H, m), 7.35 (2H, m), 4.26 (1H,
m), 4.11 (2H, m), 3.72 (1H, brd, 13.7Hz), 2.83 (1H, m), 2.45 (3H, s), 2
.42 (3H, s), 1.70 (1H, m), 1.60 1.31 (5H, m) .MS m / e 424 (MH ⁺ )

Description Example 4 4- (Benzimidazol-2-yl) piperidine (D4) 4-piperidinecarboxylic acid (5.30 g, 40 mmol), 1,2-diaminobenzene (4.32 g, 40 mmol) and polyphosphoric acid ( 40 g) was heated at 190 ° C. for 14 hours, cooled, diluted with water (150 ml), 50% KO
Basified with H to pH 8. The solution was cooled in an ice / salt bath to form a precipitate, which was collected by filtration and washed with water. The solid was dried under reduced pressure to obtain the title compound (
8.0 g, 100%). _{1H NMR (CDCl 3) 7.48 (} 2H, m), 7.09 (2H, m), 3.04 (2H, m), 2.92 (2H, m), 2
.60 (2H, m), 2.55 (1H, m), 1.95 (2H, m), 1.71 (2H, m) .MS m / e 202 (MH ⁺ )

Description 5 4- (5-Fluorobenzimidazol-2-yl) piperidine (D5) The title compound was prepared from isonipecotic acid and 2,3-diaminofluorobenzene using the method described in Description 4. . MS m / e 220 (MH ⁺ )

Description 6 4- (Benzoxazol-2-yl) piperidine (D6) The title compound was prepared from isonipecotic acid and 2-aminophenol using the method described in Description 4. MS m / e 203 (MH ⁺ )

Description Example 7 The title compound can be prepared according to the procedure described in 1H-benzimidazol-2-ylpiperazine (D7) J. Med. Chem., 1997, 40, 583-593.

Description Example 8 The title compound can be prepared according to the procedure described in 1H-indol-3-ylpiperidine (D8) J. Med. Chem., 1992, 35 (26), 4813.

Example 1 (R) -2- (1- (1- (toluene-3-sulfonyl) -pyrrolidin-2-ylmethyl) -piperidine-
4-yl) -1H-benzimidazole (E1) 2- (piperidin-4-yl) -1H-benzimidazole (109 mg, 0
． 54 mmol) under an argon atmosphere, acetonitrile (10 mL)
(R) -Toluene-3-sulfonic acid 1- (toluene-3-sulfonyl) -pyrrolidin-2-ylmethyl ester (D1) (220 mg, 0.54 mmol) in
, Potassium carbonate (150 mg, 1.1 mmol) and sodium iodide (5 m
g) was added to the mixture. The reaction mixture was heated to reflux for 12 hours. After cooling
The solvent was removed under reduced pressure and the residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate solution. The organic phase was dried over sodium sulfate and concentrated under reduced pressure. Chromatography on silica gel gave the title compound. _{1H NMR (CDCl 3) 7.65 (} 2H, m), 7.41 (2H, m), 7.22 (4H, m), 3.76 (1H, m), 3
.44 (1H, m), 3.15 2.91 (4H, m), 2.71 (1H, dd, 12.7, 3.9Hz), 2.44 (3H, s
), 2.38 2.20 (4H, m), 2.17 1.75 (6H, m) .MS m / e 439 (MH ⁺ )

The example compounds E2-E12 shown in Table 1 were converted to D1 using the procedure described in Example 1.
Or prepared with either D2 and 4-substituted piperidine or piperazine. Such reagents are commercially available or can be prepared by the methods described above.

[0021]

[Chemical 13]

Table 1

[Table 1]

The example compounds E13-E18 shown in Table 2 were prepared according to the procedure described in Example 1 using D
Prepared with 3 and 4-substituted piperidine or piperazine. Such reagents are commercially available or can be prepared by the methods described above.

[0024]

[Chemical 14]

Table 2

[Table 2]

Pharmacological data [ ³ H] -5-Carboxamidotryptamine binding to human 5-HT ₇ receptor clones expressed in vitro in 293 cells Affinity of compounds of the invention for the 5-HT ₇ receptor binding site. The WO
It can be determined by the method described in 97/29097. All compounds tested had a pKi in the range 6.0-7.9.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁷ Identification code FI theme code (reference) C07D 207/09 C07D 207/09 403/12 403/12 413/14 413/14 // C07M 7:00 C07M 7:00 (81) Designated countries EP (AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE), OA ( BF, BJ, CF, CG, CI, CM, GA, GN, GW, ML, MR, NE, SN, TD, TG), AP (GH, GM, KE, LS, MW, MZ, SD, SL, SZ, TZ, UG, ZW), EA (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), AE, AG, AL, AM, AT, AU, AZ, BA, BB, BG, BR BY, CA, CH, CN, CR, CU, CZ, DE, DK, DM, DZ, EE, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID, IL, IN, IS , JP, KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MA, MD, MG, MK, MN, MW, MX, MZ, NO, NZ, PL, PT, RO, RU, SD, SE, SG, SI, SK, SL, TJ, TM, TR, TT, TZ, UA, UG, US, UZ, VN, YU, ZA, ZW (72) Inventor Peter・ John Robert Bell C, 19.5 Abrew, Essex, Harlow, Third Avenue, New Frontiers Science Park South, Smith Crane Beecham Pharmaceuticals F-term (UK) Remarks) 4C063 AA01 AA03 BB01 BB09 CC26 CC52 DD03 DD10 EE01 4C069 AA23 CC13 4C086 AA01 AA02 AA03 AA04 BC21 BC39 BC50 BC70 GA07 GA09 GA12 GA16 MA01 MA04 NA14 ZA05 ZA12

Claims (10)

[Claims] 1. Formula (I): [Chemical 1]                        (I) [In the formula, R¹, R^TwoAnd R^ThreeAre independently hydrogen, halogen, hydroxy, C_{1- 6} Alkyl or C_1-6Is alkoxy;   m is 1 or 2;   X is nitrogen, carbon or CH;   When X is nitrogen or CH [Chemical 2] Is a single bond;   When X is carbon [Chemical 3] Is a double bond;   D is a single bond, C = O, O or CH_TwoHowever, when X is nitrogen, D
Is not oxygen;   P is phenyl, naphthyl, or selected from oxygen, nitrogen and sulfur
A 5- or 6-membered heteroaryl ring containing 1 to 3 heteroatoms
, Or containing 1 to 3 heteroatoms selected from oxygen, nitrogen and sulfur.
A benzo-fused heteroaryl ring;   R^FourIs NR⁵R⁶C optionally substituted by_1-6Alkyl, aryl,
Aryl C_1-6Alkyl, C_1-6Alkoxy, C_1-6Alkylthio, shea
No, hydroxy, nitro, halogen, CF_Three, C_TwoF₅, NR⁵R⁶, CONR ⁵ R⁶, NR⁵COR⁶, S (O)_pNR⁵R⁶, CHO, OCF_Three, SCF_Three , COR⁷, CH_TwoOR⁷, CO_TwoR⁷Or OR⁷And   p is 0, 1 or 2, and R⁵, R⁶And R⁷Independently hydrogen, C_1-6 Alkyl, aryl or aryl C_1-6Alkyl;   n means 0, 1, 2 or 3] or a pharmaceutically acceptable compound thereof
Salt. 2. A compound according to claim 1 wherein R ¹ is a methyl group meta to the sulfonamide bond and both R ² and R ³ are hydrogen. 3. The compound according to claim 1 or 2, wherein D is a single bond. 4. A compound according to any one of the preceding claims, wherein P is benzimidazole. 5. (R) -2- (1- (1- (toluene-3-sulfonyl) -pyrrolidin-2-ylmethyl) -piperidin-4-yl) -1H-benzimidazole, (S) -2- (1- (1- (toluene-3-sulfonyl) -pyrrolidin-2-ylmethyl) -piperidine-
4-yl) -1H-benzimidazole, (RS) -2- (1- (1- (toluene-3-sulfonyl) -piperidin-2-ylmethyl) -piperidine
-4-yl) -1H-benzimidazole, (R) -5-fluoro-2- (1- (1- (toluene-3-sulfonyl) -pyrrolidin-2-ylmethyl)-
Piperidin-4-yl) -1H-benzimidazole, (S) -5-fluoro-2- (1- (1- (toluene-3-sulfonyl) -pyrrolidin-2-ylmethyl)-
Piperidin-4-yl) -1H-benzimidazole, (RS) -5-fluoro-2- (1- (1- (toluene-3-sulfonyl) -piperidin-2-ylmethyl)
-Piperidin-4-yl) -1H-benzimidazole, (R) -2- (1- (1- (toluene-3-sulfonyl) -pyrrolidin-2-ylmethyl) -piperidine-
4-yl) -1H-benzoxazole, (S) -2- (1- (1- (toluene-3-sulfonyl) -pyrrolidin-2-ylmethyl) -piperidine-
4-yl) -1H-benzoxazole, (RS) -2- (1- (1- (toluene-3-sulfonyl) -piperidin-2-ylmethyl) -piperidine
-4-yl) -1H-benzoxazole, (R) -2- (4- (1- (toluene-3-sulfonyl) -pyrrolidin-2-ylmethyl) -piperazine-1
-Yl) -1H-benzimidazole, (S) -2- (4- (1- (toluene-3-sulfonyl) -pyrrolidin-2-ylmethyl) -piperazine-1
-Yl) -1H-benzimidazole, (RS) -2- (4- (1- (toluene-3-sulfonyl) -piperidin-2-ylmethyl) -piperazine-
1-yl) -1H-benzimidazole, (R) -1- (2-methoxy-phenyl) -4- (1- (toluene-3-sulfonyl) -pyrrolidin-2-ylmethyl) -piperazine, (S)- 1- (2-methoxy-phenyl) -4- (1- (toluene-3-sulfonyl) -pyrrolidin-2-ylmethyl) -piperazine, (RS) -1- (2-methoxy-phenyl) -4- (1 -(Toluene-3-sulfonyl) -piperidine-2-
(Irmethyl) -piperazine, (R) -3- (1- (1- (toluene-3-sulfonyl) -pyrrolidin-2-ylmethyl) -piperidine-
4-yl) -1H-indole, (S) -3- (1- (1- (toluene-3-sulfonyl) -pyrrolidin-2-ylmethyl) -piperidine-
4-yl) -1H-indole, (RS) -3- (1- (1- (toluene-3-sulfonyl) -piperidin-2-ylmethyl) -piperidine
4. The compound according to claim 1, which is 4-yl) -1H-indole or a pharmaceutically acceptable salt thereof. 6. Formula (II): embedded image (II) [wherein R ¹ , R ² , R ³ and m are the same as defined in formula (I) and Y represents a leaving group], and a compound represented by formula (III) : [Chemical 5] (III) [in the formula, , X, D, P, n and R ⁴ are the same as defined in formula (I)], and then, where appropriate: removing the protecting group: A method for producing a compound of formula (I) or a pharmaceutically acceptable salt thereof, characterized in that the salt is obtained. 7. A compound according to any one of claims 1 to 5 for use in therapy. 8. A compound according to any one of claims 1 to 5 for use in the treatment of CNS disorders. 9. A pharmaceutical composition comprising a compound according to any one of claims 1 to 5 and a pharmaceutically acceptable carrier or excipient. 10. Use of a compound according to any one of claims 1 to 5 in the manufacture of a medicament for use in the treatment of depression and / or sleep disorders.