WO1994004533A1 - Condensed indole derivatives as 5ht2c and 5ht2b antagonists - Google Patents

Condensed indole derivatives as 5ht2c and 5ht2b antagonists Download PDF

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Publication number
WO1994004533A1
WO1994004533A1 PCT/EP1993/002031 EP9302031W WO9404533A1 WO 1994004533 A1 WO1994004533 A1 WO 1994004533A1 EP 9302031 W EP9302031 W EP 9302031W WO 9404533 A1 WO9404533 A1 WO 9404533A1
Authority
WO
WIPO (PCT)
Prior art keywords
indole
methyl
dihydropyrrolo
pyridylcarbamoyl
hydrogen
Prior art date
Application number
PCT/EP1993/002031
Other languages
English (en)
French (fr)
Inventor
Ian Thomson Forbes
Roger Thomas Martin
Peter Ham
Thomas Paul Blackburn
Original Assignee
Smithkline Beecham Plc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GB929217674A external-priority patent/GB9217674D0/en
Priority claimed from GB939306461A external-priority patent/GB9306461D0/en
Application filed by Smithkline Beecham Plc filed Critical Smithkline Beecham Plc
Priority to AU47046/93A priority Critical patent/AU4704693A/en
Priority to EP93917699A priority patent/EP0656003A1/en
Priority to JP6505828A priority patent/JPH08500580A/ja
Publication of WO1994004533A1 publication Critical patent/WO1994004533A1/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems

Definitions

  • C 1-3 alkyl such as methyl, ethyl, n- and iso- propyl.
  • P represents a quinoline or isoquinoline residue, or a 5- or 6-membered aromatic heterocyclic ring containing up to three heteroatoms selected from nitrogen, oxygen or sulphur.
  • Suitable moieties when the ring P is a 5-membered aromatic heterocyclic ring include, for example, isothiazolyl, isoxazolyl, thiadiazolyl and triazolyl.
  • Suitable moieties when the ring P is a 6-membered aromatic heterocyclic ring include, for example, pyridyl, pyrimidyl or pyrazinyl.
  • the urea moiety can be attached at any position of the ring, preferably to the 4-position.
  • the urea moiety can be attached to a carbon or any available nitrogen atom of the ring P, preferably it is attached to a carbon atom.
  • Particularly preferred compounds of formula (I) include:
  • a and R 6 contain the appropriate functional group(s) necessary to form the moiety, -NR 5' CO when coupled, wherein R 5 ' is R 5 as defined in formula (I) or a group convertible thereto, n is as defined in formula (I), and the variables R 1' ,R 2' , R 3' , R 10' , R 11 ' , R 13' , R 14' , R 4' R 5' and R 7' are R 1 , R 2 , R 3 , R 10 , R 11 , R 13 , R 14 R 4 and R 7 respectively, as defined in formula (I), or groups convertible thereto, and thereafter optionally and as necessary and in any appropriate order, converting any R 1' , R 2' , R 3' , R 10' , R 11' , R 13' , R 14' , R 4' , R 5' and R 7' when other than R 1 , R 2 , R 3 , R 10 , R 11 , R 13 , R 14 , R 4
  • R 4' , R 5' , R 7 ', R 13' , and R 14' are as defined in formulae (II) and (III), n is as defined in formula (I), and C and D contain the appropriate functional group(s) necessary to form the indole or indoline ring substituted by R 1' , R 2' , R 3' , R 10' and R 11' as defined in formula (III), and thereafter optionally and as necessary in any appropriate order, converting any R 1' , R 2' , R 3' , R 10' , R 1 1' , R 13' , R 14' , R 4' , R 5' and R 7' when other than R 1 , R 2 , R 3 , R 10 , R 11 , R 13 , R 14 R 4 , R 5 and R 7 , to R 1 , R 2 , R 3 , R 10 , R 1 1 , R 13 , R 14 , R 4 , R 5 and R 7 , interconverting
  • R 5' is as defined above and L is a leaving group.
  • suitable leaving groups L include imidazole, halogen such as chloro or bromo or phenoxy or phenylthio optionally substituted for example with halogen.
  • reaction is suitably carried out in an inert solvent such as toluene at elevated temperature, optionally in the presence of a base.
  • the product of formula (IV) may then be cyclised as in the Fischer synthesis above.
  • Suitable examples of a group R 5' which is convertible to R 5 include
  • R 4 halo and R 7 halo may be introduced by selective halogenation of the ring P or indole/indoline ring respectively using conventional conditions.
  • N-(1-Acetyl-5-indolinyl)-2-chloro-N-trifluoroacetylallylamine (D12) (7.63 g, 22 mmol) was stirred in polyphosphoric acid (38 g) at 140° C for 1.5h. The mixture was cooled, dispersed in water (200 ml) and extracted with ethyl acetate. The extract was filtered through Kieselguhr, dried (Na2S04) and evaporated to give a dark gum (ca. 3g).
  • N-(1-Acetyl-5-indolinyl)-2-chloro-N-methylallylamine (D21) (2.1g, 7.9 mmol) was stirred in polyphosphoric acid (44g) at 140° C for 24h, cooled, dispersed in water (200 ml), and extracted with ethyl acetate. The extract was washed with brine, dried (Na 2 SO 4 ) and evaporated to give a pink solid. Chromatography on silica gel, eluting with 0-20% ethyl acetate in dichloromethane, gave:
  • N-(1,2,3,4-Tetrahydro-6-qumolyl)trifluoroacetamide (D26) (5.64g, 23.1 mmol) and acetyl chloride (2.0 ml, 28 mmol) were stirred in dichloromethane (100 ml) as pyridine (2.25 ml, 28 mmol) was added. The mixture was stirred for 0.5h, when water (100 ml) was added. After vigorous stirring for 0.25 h, it was acidified with 5M hydrochloric acid, and separated. The organic portion was washed with brine, dried (Na 2 SO 4 ), and evaporated, giving the title compound (5.24 g, 79%) as a cream solid.
  • N-(1-Acetyl-1,2,3,4-tetrahydro-6-quinolyl)trifluoroacetamide (D27) (1.85g, 6.5 mmol) was stirred in ethanol (15 ml), and sodium hydroxide (0.52g, 13.0 mmol) was added in water (3ml). The mixture was stirred at ambient temperature for 0.5 h, and then heated to reflux over 0.25 h. After 0.5 h at reflux, the mixture was cooled, acidified with 5M hydrochloric acid, basified with solid sodium carbonate, diluted with water (100 ml), and extracted with chloroform. The extract was dried (Na 2 SO 4 ) and evaporated to give the title compound (1.38g, >100%) as a brown oil containing residual chloroform (NMR).
  • the tide compound was prepared from 5-ethyl-2,3-dihydropyrrolo[2,3-f]indole (D18) and 3-pyridylisocyanate (prepared in situ from nicotinoyl azide) in 58% yield using a procedure similar to that for E1, m.p. 202-203° C.
  • the tide compound was prepared from 2-methyl-4-aminoquinoline, 1,1'-carbonyl diimidazole and 5-methyl-(2,3-dihydropyrrolo[2,3-f]indole) (D6), in 57% yield, m.p.>240° C.
  • the tide compound was prepared by the method of E23, using 5-amino-3-methylsothiazole hydrochloride (0.60g, 4 mmol), CDI (0.71g, 4.4 mmol), triethylamine (0.56ml, 4 mmol) and dihydropyrroloindole (D6) (0.69g, 4 mmol). Triethylamine was added only with the isothiazole hydrochloride.
  • the title compound was prepared from 2-methyl-4-aminopyridine anion (prepared using sodium hydride) 1,1'-carbonyld ⁇ midazole, and 5-methyl-2,3-dihydropyrrolo[2,3-f]indole in dimediylformamide using a procedure similar to that described for Example 5, in 45% yield.
  • the mixture may be compressed to tablets, or filled into hard gelatin capsules.
  • the tablet may be coated by applying a suspension of film former (e.g. HPM cellulose), pigment (e.g. titanium dioxide) and plasticiser (e.g. diethyl phthalate) and drying the film by evaporation of the solvent
  • film former e.g. HPM cellulose
  • pigment e.g. titanium dioxide
  • plasticiser e.g. diethyl phthalate
  • the film coat can comprise 2.0% to 6.0% of the tablet weight preferably about 3.0%.
  • the medicinal compound is dispersed or dissolved in the liquid carrier, with a thickening agent added, if required.
  • the formulation is then enclosed in a soft gelatin capsule by suitable technology.
  • a pharmaceutical composition for parenteral administration may be prepared by combining the following:
  • 5-HT 2C antagonists may have a number of therapeutic indications including the treatment of anxiety, migraine, depression, feeding disorders and obsessive compulsion disorders. (Curzon and Kennett, 1990; Fozard and Gray, 1989) and Alzheimer's Disease (Lawlor, 1989, J. Arch. Gen. Psychiat. Vol. 46 p.542).
  • the cells suspension 400ml was incubated with [ 3 H]-mesulergine (0.5nM) in Tris HCl buffer (pH 7.4) at 37°C for 30 minutes. Non-specific binding was measured in the presence of mianserin (10 -6 M). Ten concentrations of test drug (3 ⁇ 10 -9 to 10 -4 M final concentration) were added in a volume of 50ml. The total assay volume was 500ml. Incubation was stopped by rapid filtration using a Brandel cell harvester and radioactivity measured by scintillation counting. The IC 50 values were determined using a four parameter logistic program (DeLean 1978) and the pK i (the negative logarithm of the inhibition constant) calculated from the Cheng Prusoff equation where:
  • mCPP-induced hypolocomotion was measured in automated locomotion cages of dimensions 56 cm long ⁇ 161 ⁇ 2 cm wide ⁇ 25 cm high and made of black perspex. Two photobeams traversed the wi th of the cages at either end at ground level. Sequential breaking of these beams allowed the measurement of cage transits.
  • mice Male Sprague Dawley rats (200-250g) (Charles River) were housed in groups of six. They were given drugs orally 1h pretest and 40 mins later mCPP (7 mg/kg i.p.). After a further 20 min they were placed in individual automated cages in groups of four under red light in an adjacent room. After 10 min the test was terminated. Reversal of mCPP-induced hypolocomotion was considered as evidence of in vivo central 5-HT 2C receptor antagonist properties.
  • the compound of Example 2 showed a significant increase in social interaction at doses of 10 mg/kg.
  • Rats are trained on a variable interval 30 sec schedule (VT30) to press a lever in order to obtain food reward.
  • the 5 min sessions of the Nl 3 0 schedule alternate with 2-5 min of a schedule (FR5) in which every 5th lever press is followed by presentation of a food pellet paired with a 0.5 sec mild footshock.
  • the total study lasts approximately 30 mins.
  • Rats typically respond with high rates of lever pressing under the VI30 schedule and low response rates under the FR5 'conflict' session.
  • Anxiolytic drugs increase the suppressed response rates of rats in a 'conflict' session.
  • Drugs are administered intraperitoneally or orally to groups of 3-8 rats 30 min before testing.
  • the results are expressed as the percentage increase in the square root of the total number of lever presses in the FR5 'conflict' session. Square root transformation is necessary to normalise the data for statistical analysis using parametric methods.
  • the compound of Example 2 showed a significant increase in responding in the 'conflict' session at dose levels in the range 5 mg/kg p.o.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Indole Compounds (AREA)
  • Heat Sensitive Colour Forming Recording (AREA)
PCT/EP1993/002031 1992-08-20 1993-07-29 Condensed indole derivatives as 5ht2c and 5ht2b antagonists WO1994004533A1 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
AU47046/93A AU4704693A (en) 1992-08-20 1993-07-29 Condensed indole derivatives as 5HT-2C and 5HT-2B antagonists
EP93917699A EP0656003A1 (en) 1992-08-20 1993-07-29 Condensed indole derivatives as 5ht2c and 5ht2b antagonists
JP6505828A JPH08500580A (ja) 1992-08-20 1993-07-29 ５ｈｔ▲下２ｃ▼および５ｈｔ▲下２ｂ▼拮抗薬用縮合インドール誘導体

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GB9217674.2 1992-08-20
GB929217674A GB9217674D0 (en) 1992-08-20 1992-08-20 Novel compounds
GB9306461.6 1993-03-29
GB939306461A GB9306461D0 (en) 1993-03-29 1993-03-29 Novel compounds

Publications (1)

Publication Number Publication Date
WO1994004533A1 true WO1994004533A1 (en) 1994-03-03

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PCT/EP1993/002031 WO1994004533A1 (en) 1992-08-20 1993-07-29 Condensed indole derivatives as 5ht2c and 5ht2b antagonists

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EP (1) EP0656003A1 (enrdf_load_stackoverflow)
JP (1) JPH08500580A (enrdf_load_stackoverflow)
CN (1) CN1086819A (enrdf_load_stackoverflow)
AP (1) AP9300560A0 (enrdf_load_stackoverflow)
AU (1) AU4704693A (enrdf_load_stackoverflow)
CA (1) CA2142721A1 (enrdf_load_stackoverflow)
IL (1) IL106737A0 (enrdf_load_stackoverflow)
MA (1) MA22955A1 (enrdf_load_stackoverflow)
MX (1) MX9305037A (enrdf_load_stackoverflow)
NZ (1) NZ254785A (enrdf_load_stackoverflow)
SI (1) SI9300438A (enrdf_load_stackoverflow)
TW (1) TW248557B (enrdf_load_stackoverflow)
WO (1) WO1994004533A1 (enrdf_load_stackoverflow)

Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994022871A1 (en) * 1993-03-29 1994-10-13 Smithkline Beecham Plc THIENO-INDOLE DERIVATIVES AS 5HT2c AND 5HT2b ANTAGONISTS
WO1995001976A1 (en) * 1993-07-06 1995-01-19 Smithkline Beecham Plc Indoline derivatives as 5ht2c antagonists
WO1995021844A1 (en) * 1994-02-10 1995-08-17 Smithkline Beecham Plc 5ht2b receptor antagonists condensed indoles
WO1995029177A1 (en) * 1994-04-23 1995-11-02 Smithkline Beecham P.L.C. Tricyclic derivatives as 5ht2c and 5ht2b antagonists
WO1996011929A1 (en) * 1994-10-12 1996-04-25 Smithkline Beecham Plc Biheteroaryl-carbonyl and carboxamide derivatives with 5ht 2c/2b antagonists activity
WO1996011930A1 (en) * 1994-10-18 1996-04-25 Smithkline Beecham P.L.C. Cns-active pyridinylurea derivatives
WO1996023783A1 (en) * 1995-02-02 1996-08-08 Smithkline Beecham Plc Indole derivatives as 5-ht receptor antagonist
WO1996023769A3 (en) * 1995-02-02 1996-10-24 Smithkline Beecham Plc Heterocyclic compounds possessing 5ht2c receptor antagonist activity
WO1997008167A1 (en) * 1995-08-26 1997-03-06 Smithkline Beecham P.L.C. 5ht2c and 5ht2b antagonists
WO1997037989A1 (en) * 1996-04-04 1997-10-16 Smithkline Beecham Plc Indole derivatives as 5-ht receptor antagonist
WO1997048700A1 (en) * 1996-06-20 1997-12-24 Smithkline Beecham Plc Indoline derivatives useful as 5-ht-2c receptor antagonists
WO1997048699A1 (en) * 1996-06-20 1997-12-24 Smithkline Beecham Plc Indoline derivatives useful as 5-ht-2c receptor antagonists
WO1998024785A1 (en) * 1996-12-02 1998-06-11 Fujisawa Pharmaceutical Co., Ltd. Indole-urea derivatives with 5-ht antagonist properties
WO1999025709A1 (en) * 1997-11-18 1999-05-27 Smithkline Beecham P.L.C. Isoquinoline derivatives and their therapeutical use
EP1348704A1 (fr) * 2002-03-27 2003-10-01 Les Laboratoires Servier Dérivés d'indole possédant des propriétés antagonistes 5-HT2C, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent
WO2004057338A1 (en) * 2002-12-23 2004-07-08 Bayer Healthcare Ag Diagnostics and therapeutics for diseases assosciated with 5-hydroxytryptamine (serotonin) receptor 2b (5-hteb)
WO2004081010A1 (en) * 2003-03-11 2004-09-23 Glaxo Group Limited Compounds having activity at 5ht2c receptor and uses thereof
KR100470691B1 (ko) * 2000-04-13 2005-03-07 르 라보레또레 쎄르비에르 시클로부타인돌카르복사미드 화합물, 이의 제조 방법 및이를 함유하는 약제 조성물
EP2036564A1 (en) 1999-12-06 2009-03-18 H.Lundbeck A/S The combination of a serotonin reuptake inhibitor and a 5-HT2C antagonist, inverse agonist or partial agonist
WO2014049153A1 (en) * 2012-09-28 2014-04-03 INSERM (Institut National de la Santé et de la Recherche Médicale) Antagonists of the 5-ht2b receptor for use in the prevention or treatment of spasticity
WO2022006365A3 (en) * 2020-07-02 2022-02-10 Purdue Research Foundation Tetrahydro-3h-pyrazolo quinolone and tetrahydro-3h-pyrrolo[3,2-f]quinoline-containing compounds and uses thereof

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992005170A1 (en) * 1990-09-13 1992-04-02 Beecham Group Plc Indole ureas as 5 ht receptor antagonist

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992005170A1 (en) * 1990-09-13 1992-04-02 Beecham Group Plc Indole ureas as 5 ht receptor antagonist

Cited By (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994022871A1 (en) * 1993-03-29 1994-10-13 Smithkline Beecham Plc THIENO-INDOLE DERIVATIVES AS 5HT2c AND 5HT2b ANTAGONISTS
US5834494A (en) * 1993-07-06 1998-11-10 Smithkline Beecham P.L.C. Pyridylcarbamoyl Indolines
WO1995001976A1 (en) * 1993-07-06 1995-01-19 Smithkline Beecham Plc Indoline derivatives as 5ht2c antagonists
WO1995021844A1 (en) * 1994-02-10 1995-08-17 Smithkline Beecham Plc 5ht2b receptor antagonists condensed indoles
WO1995029177A1 (en) * 1994-04-23 1995-11-02 Smithkline Beecham P.L.C. Tricyclic derivatives as 5ht2c and 5ht2b antagonists
WO1996011929A1 (en) * 1994-10-12 1996-04-25 Smithkline Beecham Plc Biheteroaryl-carbonyl and carboxamide derivatives with 5ht 2c/2b antagonists activity
US5866586A (en) * 1994-10-18 1999-02-02 Smithkline Beecham P.L.C. CNS-active pyridinylurea derivatives
WO1996011930A1 (en) * 1994-10-18 1996-04-25 Smithkline Beecham P.L.C. Cns-active pyridinylurea derivatives
US5990133A (en) * 1995-02-02 1999-11-23 Smithkline Beecham P.L.C. Indole derivatives as 5-HT receptor antagonist
US6638953B2 (en) 1995-02-02 2003-10-28 Smithkline Beecham P.L.C. Indole derivatives as 5-HT receptor antagonist
WO1996023769A3 (en) * 1995-02-02 1996-10-24 Smithkline Beecham Plc Heterocyclic compounds possessing 5ht2c receptor antagonist activity
US6235758B1 (en) * 1995-02-02 2001-05-22 Smithkline Beecham P.L.C. Indole derivatives as 5-HT receptor antagonist
AP657A (en) * 1995-02-02 1998-08-06 Smithkline Beecham Plc Indole derivatives as 5-HT receptor antagonist.
WO1996023783A1 (en) * 1995-02-02 1996-08-08 Smithkline Beecham Plc Indole derivatives as 5-ht receptor antagonist
US5972937A (en) * 1995-02-02 1999-10-26 Smithkline Beecham P.L.C. Heterocyclic compounds possessing 5HT2C receptor antagonist activity
WO1997008167A1 (en) * 1995-08-26 1997-03-06 Smithkline Beecham P.L.C. 5ht2c and 5ht2b antagonists
WO1997037989A1 (en) * 1996-04-04 1997-10-16 Smithkline Beecham Plc Indole derivatives as 5-ht receptor antagonist
US6028085A (en) * 1996-04-04 2000-02-22 Smithkline Beecham Plc Indole derivatives as 5-HT receptor antagonist
WO1997048699A1 (en) * 1996-06-20 1997-12-24 Smithkline Beecham Plc Indoline derivatives useful as 5-ht-2c receptor antagonists
US6369060B1 (en) 1996-06-20 2002-04-09 Smithkline Beecham P.L.C. Indoline derivatives useful as 5-HT-2C receptor antagonists
WO1997048700A1 (en) * 1996-06-20 1997-12-24 Smithkline Beecham Plc Indoline derivatives useful as 5-ht-2c receptor antagonists
US6313145B1 (en) 1996-06-20 2001-11-06 Smithkline Beecham P.L.C. Indoline derivatives useful as 5-HT-2C receptor antagonists
WO1998024785A1 (en) * 1996-12-02 1998-06-11 Fujisawa Pharmaceutical Co., Ltd. Indole-urea derivatives with 5-ht antagonist properties
WO1999025709A1 (en) * 1997-11-18 1999-05-27 Smithkline Beecham P.L.C. Isoquinoline derivatives and their therapeutical use
US6274594B1 (en) 1997-11-18 2001-08-14 Smithkline Beecham P.L.C. Isoquinoline derivatives and their therapeutical use
EP2036564A1 (en) 1999-12-06 2009-03-18 H.Lundbeck A/S The combination of a serotonin reuptake inhibitor and a 5-HT2C antagonist, inverse agonist or partial agonist
KR100470691B1 (ko) * 2000-04-13 2005-03-07 르 라보레또레 쎄르비에르 시클로부타인돌카르복사미드 화합물, 이의 제조 방법 및이를 함유하는 약제 조성물
EP1348704A1 (fr) * 2002-03-27 2003-10-01 Les Laboratoires Servier Dérivés d'indole possédant des propriétés antagonistes 5-HT2C, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent
FR2837823A1 (fr) * 2002-03-27 2003-10-03 Servier Lab Nouveaux derives d'indoline, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
AU2003203287B2 (en) * 2002-03-27 2008-08-28 Les Laboratoires Servier New indoline compounds, a process for their preparation and pharmaceutical compositions containing them
WO2004057338A1 (en) * 2002-12-23 2004-07-08 Bayer Healthcare Ag Diagnostics and therapeutics for diseases assosciated with 5-hydroxytryptamine (serotonin) receptor 2b (5-hteb)
WO2004081010A1 (en) * 2003-03-11 2004-09-23 Glaxo Group Limited Compounds having activity at 5ht2c receptor and uses thereof
WO2014049153A1 (en) * 2012-09-28 2014-04-03 INSERM (Institut National de la Santé et de la Recherche Médicale) Antagonists of the 5-ht2b receptor for use in the prevention or treatment of spasticity
WO2022006365A3 (en) * 2020-07-02 2022-02-10 Purdue Research Foundation Tetrahydro-3h-pyrazolo quinolone and tetrahydro-3h-pyrrolo[3,2-f]quinoline-containing compounds and uses thereof

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Publication number Publication date
AP9300560A0 (en) 1995-02-19
NZ254785A (en) 1995-09-26
MA22955A1 (fr) 1994-04-01
CN1086819A (zh) 1994-05-18
SI9300438A (en) 1994-03-31
JPH08500580A (ja) 1996-01-23
EP0656003A1 (en) 1995-06-07
AU4704693A (en) 1994-03-15
MX9305037A (es) 1994-03-31
TW248557B (enrdf_load_stackoverflow) 1995-06-01
CA2142721A1 (en) 1994-03-03
IL106737A0 (en) 1994-05-30

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