WO2006136284A1 - Pharmaceutical composition comprising a 1-(3-chlorophenyl)-3-alkylpiperazine for treating apetite disorder - Google Patents
Pharmaceutical composition comprising a 1-(3-chlorophenyl)-3-alkylpiperazine for treating apetite disorder Download PDFInfo
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- WO2006136284A1 WO2006136284A1 PCT/EP2006/005390 EP2006005390W WO2006136284A1 WO 2006136284 A1 WO2006136284 A1 WO 2006136284A1 EP 2006005390 W EP2006005390 W EP 2006005390W WO 2006136284 A1 WO2006136284 A1 WO 2006136284A1
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- Prior art keywords
- acid
- pharmaceutical composition
- formula
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- chlorophenyl
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 18
- 150000003839 salts Chemical class 0.000 claims abstract description 12
- 150000007522 mineralic acids Chemical class 0.000 claims abstract description 10
- 150000007524 organic acids Chemical class 0.000 claims abstract description 10
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 32
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 11
- 208000008589 Obesity Diseases 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 235000020824 obesity Nutrition 0.000 claims description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 9
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 8
- 208000027559 Appetite disease Diseases 0.000 claims description 7
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 7
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 claims description 3
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 3
- 208000032841 Bulimia Diseases 0.000 claims description 3
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- 239000001358 L(+)-tartaric acid Substances 0.000 claims description 3
- 235000011002 L(+)-tartaric acid Nutrition 0.000 claims description 3
- FEWJPZIEWOKRBE-LWMBPPNESA-N L-(+)-Tartaric acid Natural products OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 claims description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 3
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- 239000001117 sulphuric acid Substances 0.000 claims description 3
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 3
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 claims 4
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 abstract 1
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- VHFVKMTVMIZMIK-UHFFFAOYSA-N 1-(3-chlorophenyl)piperazine Chemical compound ClC1=CC=CC(N2CCNCC2)=C1 VHFVKMTVMIZMIK-UHFFFAOYSA-N 0.000 description 6
- 230000000338 anxiogenic effect Effects 0.000 description 6
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- YZTJYBJCZXZGCT-UHFFFAOYSA-N phenylpiperazine Chemical compound C1CNCCN1C1=CC=CC=C1 YZTJYBJCZXZGCT-UHFFFAOYSA-N 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
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- KKIMDKMETPPURN-UHFFFAOYSA-N 1-(3-(trifluoromethyl)phenyl)piperazine Chemical compound FC(F)(F)C1=CC=CC(N2CCNCC2)=C1 KKIMDKMETPPURN-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
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- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
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- 0 *C(C1)NCCN1c1cc(Cl)ccc1 Chemical compound *C(C1)NCCN1c1cc(Cl)ccc1 0.000 description 1
- DGNLGWJZZZOYPT-UHFFFAOYSA-N 1-[3-(trifluoromethyl)phenyl]piperazin-1-ium;chloride Chemical compound [Cl-].FC(F)(F)C1=CC=CC(N2CC[NH2+]CC2)=C1 DGNLGWJZZZOYPT-UHFFFAOYSA-N 0.000 description 1
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- 101710138091 5-hydroxytryptamine receptor 2A Proteins 0.000 description 1
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 1
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- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
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- OMWUYYTWPMWEBO-UHFFFAOYSA-N sodium;carboxymethylazanide Chemical compound [Na+].[NH-]CC(O)=O OMWUYYTWPMWEBO-UHFFFAOYSA-N 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
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- 235000002906 tartaric acid Nutrition 0.000 description 1
- PHLBKPHSAVXXEF-UHFFFAOYSA-N trazodone Chemical compound ClC1=CC=CC(N2CCN(CCCN3C(N4C=CC=CC4=N3)=O)CC2)=C1 PHLBKPHSAVXXEF-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
Definitions
- the present invention relates to the pharmaceutical use of a 1-(3- chlorophenyl)-3-alkylpiperazine having a chiral centre (S) and of 5 pharmaceutically acceptable acid addition salts thereof.
- the present invention relates to the use of a 1-(3- chlorophenyl)-3-alkylpiperazine having a chiral centre (S) and of pharmaceutically acceptable acid addition salts thereof in the treatment of appetite disorders.
- Patent US 3 253 989 describes an N-phenylpiperazine of formula
- R is H, m-CI, p-CI, m-CH3 or p-CH3, endowed with anorexigenic activity.
- N-phenylpiperazines endowed with hypophagia- 20 inducing activity are described in the literature, for example m- trifluoromethyl phenylpiperazine (TFMPP) (Eur J Pharmacol, 1987; 141 : 429).
- TFMPP m- trifluoromethyl phenylpiperazine
- N-phenylpiperazines are limited by CNS side- effects which cause changes in mood and behaviour leading to 25 induction of anxiety states which often result in panic attacks.
- Obesity is defined in terms of BMI (Body Mass Index) calculated as weight (kg)/[height (m)] 2 .
- BMI Body Mass Index
- a BMI below 25 is considered normal, from 25 to 29.9 is considered overweight, whereas a BMI above 30 is an indicator of obesity.
- One of the commonest causes of an overweight condition and of obesity is an excessive calorie intake which is not utilized by the body, but is accumulated in the adipose tissue.
- WO 93/14091 describes a 1-(3-chlorophenyl)-3-alkylpiperazine of formula (I):
- R is an alkyl group having from 1 to 3 carbon atoms, as an intermediate for preparing alkyl derivatives of trazodone.
- a first aspect of the present invention therefore relates to the pharmaceutical use of a 1-(3-chlorophenyl)-3-alkylpiperazine of formula (I), in racemic (R 1 S) form or in the form of the (S) enantiomer,
- R is a linear or branched alkyl group having from 1 to 3 carbon atoms, or of an addition salt thereof with a pharmaceutically acceptable organic or inorganic acid.
- this pharmaceutical use comprises the treatment of an appetite disorder.
- said appetite disorder is selected from the group comprising hyperphagia, bulimia and obesity.
- a second aspect of the present invention relates to a pharmaceutical composition that includes a therapeutically effective amount of a 1-(3- chlorophenyl)-3-alkylpiperazine of formula (I), in (R 1 S) racemic form or in the form of (S) enantiomer,
- R is a linear or branched alkyl group having from 1 to 3 carbon atoms, or of an addition salt thereof with a pharmaceutically acceptable organic or inorganic acid, and at least one pharmaceutically acceptable excipient.
- R is methyl or ethyl. Even more preferably, R is methyl.
- the compound of formula (I) is an enantiomer of (S) configuration.
- said organic acid is selected from the group comprising maleic, methanesulphonic, paratoluenesulphonic, succinic and citric acid.
- said inorganic acid is typically selected from the group comprising hydrochloric, hydrobromic, phosphoric and sulphuric acid.
- the preferred acid is hydrochloric acid.
- optically active acids such as lactic acid and tartaric acid, both in the natural L(+) form.
- the preferred acid is L(+) tartaric acid.
- the compound of formula (I) in racemic (R 1 S) form can be prepared by known techniques, for example reaction scheme 3 described in WO 93/14091.
- the enantiomer in the (S) configuration can also be obtained by known techniques, for example those described by M. Giannangeli et al. (loc. cit.).
- the anxiogenic activity of the compounds of the present invention was investigated by means of the social interaction test in the rat, which, as is known by a person skilled in the art, represents an experimental model that is predictive of the effects in humans.
- the normal social interaction of rats is generally suppressed when the animals are put in an unfamiliar environment.
- Measurement of the time spent by pairs of animals in interacting with one another and exploring their surroundings constitutes a model for verifying the action of substances that influence social behaviour.
- the social interaction test shows numerous similarities between the behaviour exhibited by the rats and anxiety states in humans and proves to be a useful tool for demonstrating effects on mood, both of the anxiogenic and of the anxiolytic type.
- hypophagia-inducing activity of the compounds of formula (I) was demonstrated by verifying the food consumption of food-deprived rats.
- Verification of the consumption of food in food-deprived rats represents a condition that reproduces the complex system regulating the sensation of hunger and the intake of food in humans. Fasting in fact introduces many physiological changes that can lead to activation of the circuits that are specifically dedicated to the control of food intake. As is well known, the use of this model constitutes a valid tool for identifying substances capable of interfering with appetite disorders and can be used in particular for monitoring conditions such as hyperphagia, bulimia and obesity.
- compositions of the present invention are prepared as suitable dosage forms containing an effective dose of at least one compound of formula (I) or of a pharmaceutically acceptable salt thereof with an organic or inorganic acid and at least one pharmaceutically acceptable inert ingredient.
- suitable dosage forms are tablets, capsules, coated tablets, granules, solutions and syrups for oral administration; medicated patches for transdermal administration; suppositories for rectal administration, and injectable sterile solutions.
- Other suitable dosage forms are those with extended release and those based on liposomes, for administration by the oral, injectable or transdermal route.
- the dosage forms can also contain other conventional ingredients such as: preservatives, stabilizers, surfactants, buffers, salts for regulating osmotic pressure, emulsifiers, sweeteners, colorants, flavourings and the like.
- the pharmaceutical composition of the present invention can contain other pharmacologically active ingredients, whose concomitant administration is useful.
- the amount of compound of formula (I) or of a pharmaceutically acceptable acid addition salt thereof in the pharmaceutical composition of the present invention can vary over a wide range depending on known factors, for example the type of pathology, the severity of the disease, the patient's body weight, the dosage form, the chosen route of administration, the number of daily doses and the efficacy of the chosen compound of formula (I). However, determination of the optimum amount is a simple and routine matter for a person skilled in the art.
- the amount of compound of formula (I) or of a pharmaceutically acceptable acid addition salt thereof in the pharmaceutical composition of the present invention will be such as to ensure a level of administration between 0.001 and 100 mg/kg/day.
- the level of administration is between 0.05 and 50 mg/kg/day, and even more preferably between 0.1 and 10 mg/kg/day.
- the dosage forms of the pharmaceutical composition of the present invention can be prepared by techniques that are well known to a pharmaceutical chemist, and include mixing, granulation, compression, dissolution, sterilization and the like.
- the compounds of the present invention can be prepared by methods that are known to a person skilled in the art.
- the racemic compound 1 was prepared by the method described in Example 4 of WO 93/14091 whereas the two enantiomers 2 and 3 were separated with (+) and (-)-tartaric acid respectively, as described by M. Giannangeli et al. (loc. cit.).
- the aforesaid methods can also be used for preparing the compounds of the present invention in which R is ethyl or propyl.
- the animals were kept in a room with a controlled cycle of light and darkness (6:00-18:00). To promote acclimatization and eliminate responses induced by stress conditions, the rats were handled and were injected daily with the vehicle (water) for the four days preceding administration of the test compounds.
- the animals were kept in a room with a controlled cycle of light and darkness (6:00-18:00). Before the test, which was carried out at 9:30 corresponding to daytime, the animals were deprived of food for 24 h. At the end of the fasting period, the animals were treated orally with the test compounds (10 mg/kg) in an aqueous vehicle and, immediately after treatment, a pre-weighed amount of food was made available. One hour after treatment, the food consumption was evaluated by weighing the amount of food remaining. The control animals were treated orally with the vehicle (water) used for administering the test compounds.
- Fig. 2A shows that the amount of food consumed by the animals treated with the racemic compound (compound 1) of the invention is approx. 28% lower than that consumed by the control animals.
- Fig. 2B shows that the amounts of food consumed by the animals treated with the (S) enantiomer (compound 2) and with the (R) enantiomer of the invention are approx. 75-80% and 20% lower, respectively, than that consumed by the control animals.
- Fig. 2B therefore shows that the hypophagia-inducing activity of the racemic compound of the invention can be attributed almost entirely to the (S) enantiomer.
- a tablet containing a compound of the present invention as active principle has the following composition:
- a vial contains 5 ml of an injectable solution containing a compound of the present invention as active principle.
- Said solution has the following composition: Active principle 25 mg
- a sachet contains 5.23 g of water-dispersible granules containing a compound of the present invention as active principle. Said granules have the following composition: Active principle 50 mg
Abstract
Description
Claims
Priority Applications (16)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US11/910,559 US7879836B2 (en) | 2005-06-24 | 2006-06-02 | Pharmaceutical composition comprising a 1-(3-chlorophenyl)-3-alkylpiperazine for treating appetite disorder |
AT06754160T ATE431146T1 (en) | 2005-06-24 | 2006-06-02 | PHARMACEUTICAL COMPOSITION CONTAINING A 1-(3-CHLORPHENYL)-3-ALKYLPIPERAZINE FOR THE TREATMENT OF APPETITE DISORDERS |
EP06754160A EP1893208B1 (en) | 2005-06-24 | 2006-06-02 | Pharmaceutical composition comprising a 1-(3-chlorophenyl)-3-alkylpiperazine for treating apetite disorder |
DE602006006827T DE602006006827D1 (en) | 2005-06-24 | 2006-06-02 | PHARMACEUTICAL COMPOSITION WITH A 1- (3-CHLOROPHENYL) -3-ALKYLPIPERAZINE FOR THE TREATMENT OF APPETITOR DISORDERS |
JP2008517359A JP5142991B2 (en) | 2005-06-24 | 2006-06-02 | Pharmaceutical composition for treating appetite disorders comprising 1- (3-chlorophenyl) -3-alkylpiperazine |
AU2006261296A AU2006261296B9 (en) | 2005-06-24 | 2006-06-02 | Pharmaceutical composition comprising a 1-(3-chlorophenyl)-3-alkylpiperazine for treating apetite disorder |
BRPI0611719-8A BRPI0611719A2 (en) | 2005-06-24 | 2006-06-02 | pharmaceutical use of a 1- (3-chlorophenyl) -3-alkylpiperazine, and, pharmaceutical composition |
CA2604584A CA2604584C (en) | 2005-06-24 | 2006-06-02 | Pharmaceutical composition comprising a 1-(3-chlorophenyl)-3-alkylpiperazine for treating apetite disorder |
MX2007014396A MX2007014396A (en) | 2005-06-24 | 2006-06-02 | Pharmaceutical composition comprising a 1-(3-chlorophenyl)-3- alkylpiperazine for treating apetite disorder. |
CN2006800148322A CN101171011B (en) | 2005-06-24 | 2006-06-02 | Pharmaceutical composition comprising a 1-(3-chlorophenyl)-3-alkylpiperazine for treating apetite disorder |
EA200800125A EA012443B1 (en) | 2005-06-24 | 2006-06-02 | Pharmaceutical composition comprising a 1-(3-chlorophenyl)-3-alkylpiperazine for treating appetite disorder |
PL06754160T PL1893208T3 (en) | 2005-06-24 | 2006-06-02 | Pharmaceutical composition comprising a 1-(3-chlorophenyl)-3-alkylpiperazine for treating apetite disorder |
DK06754160T DK1893208T3 (en) | 2005-06-24 | 2006-06-02 | Pharmaceutical composition with a 1- (3-chlorophenyl) -3-alkylpiperazine for the treatment of appetite disorders |
KR1020077030116A KR101324689B1 (en) | 2005-06-24 | 2006-06-02 | Pharmaceutical composition comprising a 1-(3-chlorophenyl)-3-alkylpiperazine for treating apetite disorder |
IL186334A IL186334A (en) | 2005-06-24 | 2007-10-07 | Pharmaceutical composition comprising a 1-(3-chlorophenyl)-3-alkylpiperazine for treating appetite disorder |
HK08104469A HK1111080A1 (en) | 2005-06-24 | 2008-04-22 | Pharmaceutical composition comprising a 1-(3-chlorophenyl)-3- alkylpiperazine for treating apetite disorder |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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IT001193A ITMI20051193A1 (en) | 2005-06-24 | 2005-06-24 | PHARMACEUTICAL USE OF A 1-3-CHLOROFENYL-3-ALCHILPIPERAZINE |
ITMI2005A001193 | 2005-06-24 |
Publications (1)
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WO2006136284A1 true WO2006136284A1 (en) | 2006-12-28 |
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PCT/EP2006/005390 WO2006136284A1 (en) | 2005-06-24 | 2006-06-02 | Pharmaceutical composition comprising a 1-(3-chlorophenyl)-3-alkylpiperazine for treating apetite disorder |
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US (1) | US7879836B2 (en) |
EP (1) | EP1893208B1 (en) |
JP (1) | JP5142991B2 (en) |
KR (1) | KR101324689B1 (en) |
CN (1) | CN101171011B (en) |
AR (1) | AR054491A1 (en) |
AT (1) | ATE431146T1 (en) |
AU (1) | AU2006261296B9 (en) |
BR (1) | BRPI0611719A2 (en) |
CA (1) | CA2604584C (en) |
DE (1) | DE602006006827D1 (en) |
DK (1) | DK1893208T3 (en) |
EA (1) | EA012443B1 (en) |
ES (1) | ES2325744T3 (en) |
GE (1) | GEP20094787B (en) |
HK (1) | HK1111080A1 (en) |
IL (1) | IL186334A (en) |
IT (1) | ITMI20051193A1 (en) |
MX (1) | MX2007014396A (en) |
PL (1) | PL1893208T3 (en) |
PT (1) | PT1893208E (en) |
SI (1) | SI1893208T1 (en) |
UA (1) | UA89236C2 (en) |
WO (1) | WO2006136284A1 (en) |
Citations (4)
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US3253989A (en) * | 1963-02-11 | 1966-05-31 | American Cyanamid Co | Process for producing anorexia |
US3637705A (en) * | 1968-10-01 | 1972-01-25 | Abbott Lab | N-3 4-dihalo phenyl piperazines |
US3929792A (en) * | 1972-09-29 | 1975-12-30 | D Emile Bouchara | Phenylpiperazine derivatives, process for their preparation and applications thereof |
WO1993014091A1 (en) * | 1992-01-17 | 1993-07-22 | Istituto Ricerca Francesco Angelini S.P.A. | Alkyl derivatives of trazodone with cns activity |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SE9904723D0 (en) * | 1999-12-22 | 1999-12-22 | Carlsson A Research Ab | New modulators of dopamine neurotransmission II |
CN1809545A (en) * | 2003-06-20 | 2006-07-26 | 艾尼纳制药公司 | N-phenyl-piperazine derivatives and methods of prophylaxis or treatment of 5HT2c |
-
2005
- 2005-06-24 IT IT001193A patent/ITMI20051193A1/en unknown
-
2006
- 2006-06-02 CN CN2006800148322A patent/CN101171011B/en not_active Expired - Fee Related
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- 2006-06-02 WO PCT/EP2006/005390 patent/WO2006136284A1/en active Application Filing
- 2006-06-02 GE GEAP200610483A patent/GEP20094787B/en unknown
- 2006-06-02 KR KR1020077030116A patent/KR101324689B1/en not_active IP Right Cessation
- 2006-06-02 CA CA2604584A patent/CA2604584C/en not_active Expired - Fee Related
- 2006-06-02 AT AT06754160T patent/ATE431146T1/en active
- 2006-06-02 JP JP2008517359A patent/JP5142991B2/en not_active Expired - Fee Related
- 2006-06-02 MX MX2007014396A patent/MX2007014396A/en active IP Right Grant
- 2006-06-02 US US11/910,559 patent/US7879836B2/en not_active Expired - Fee Related
- 2006-06-02 DK DK06754160T patent/DK1893208T3/en active
- 2006-06-02 SI SI200630354T patent/SI1893208T1/en unknown
- 2006-06-02 EP EP06754160A patent/EP1893208B1/en not_active Not-in-force
- 2006-06-02 ES ES06754160T patent/ES2325744T3/en active Active
- 2006-06-02 PT PT06754160T patent/PT1893208E/en unknown
- 2006-06-02 EA EA200800125A patent/EA012443B1/en not_active IP Right Cessation
- 2006-06-02 DE DE602006006827T patent/DE602006006827D1/en active Active
- 2006-06-02 AU AU2006261296A patent/AU2006261296B9/en not_active Ceased
- 2006-06-02 PL PL06754160T patent/PL1893208T3/en unknown
- 2006-06-02 BR BRPI0611719-8A patent/BRPI0611719A2/en not_active IP Right Cessation
- 2006-06-22 AR ARP060102671A patent/AR054491A1/en unknown
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- 2007-10-07 IL IL186334A patent/IL186334A/en not_active IP Right Cessation
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Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
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US3253989A (en) * | 1963-02-11 | 1966-05-31 | American Cyanamid Co | Process for producing anorexia |
US3637705A (en) * | 1968-10-01 | 1972-01-25 | Abbott Lab | N-3 4-dihalo phenyl piperazines |
US3929792A (en) * | 1972-09-29 | 1975-12-30 | D Emile Bouchara | Phenylpiperazine derivatives, process for their preparation and applications thereof |
WO1993014091A1 (en) * | 1992-01-17 | 1993-07-22 | Istituto Ricerca Francesco Angelini S.P.A. | Alkyl derivatives of trazodone with cns activity |
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Title |
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GIANNANGELI M ET AL: "Effect of Mocifications of the Alkylpiperazine Moiety of Trazodone on 5HT2A and alpha-1 Receptor Binding Affinity", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY. WASHINGTON, US, vol. 42, no. 3, 1999, pages 336 - 345, XP002142123, ISSN: 0022-2623 * |
Also Published As
Publication number | Publication date |
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MX2007014396A (en) | 2008-02-12 |
DE602006006827D1 (en) | 2009-06-25 |
ITMI20051193A1 (en) | 2006-12-25 |
JP2008546725A (en) | 2008-12-25 |
IL186334A0 (en) | 2008-08-07 |
ATE431146T1 (en) | 2009-05-15 |
CA2604584A1 (en) | 2006-12-28 |
US7879836B2 (en) | 2011-02-01 |
AU2006261296B9 (en) | 2011-01-20 |
GEP20094787B (en) | 2009-09-25 |
EA200800125A1 (en) | 2008-04-28 |
EA012443B1 (en) | 2009-10-30 |
KR101324689B1 (en) | 2013-11-04 |
AU2006261296A1 (en) | 2006-12-28 |
DK1893208T3 (en) | 2009-08-31 |
CA2604584C (en) | 2013-07-16 |
BRPI0611719A2 (en) | 2012-07-31 |
AR054491A1 (en) | 2007-06-27 |
AU2006261296B2 (en) | 2010-12-16 |
UA89236C2 (en) | 2010-01-11 |
CN101171011B (en) | 2011-04-13 |
CN101171011A (en) | 2008-04-30 |
PL1893208T3 (en) | 2009-10-30 |
KR20080026115A (en) | 2008-03-24 |
SI1893208T1 (en) | 2009-10-31 |
EP1893208A1 (en) | 2008-03-05 |
EP1893208B1 (en) | 2009-05-13 |
HK1111080A1 (en) | 2008-08-01 |
IL186334A (en) | 2011-02-28 |
ES2325744T3 (en) | 2009-09-15 |
JP5142991B2 (en) | 2013-02-13 |
PT1893208E (en) | 2009-06-26 |
US20090054461A1 (en) | 2009-02-26 |
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