Title:
1-TRIFLUOROMETHYL-4-HYDROXY-7-PIPERIDINYL-AMINOMETHYLCHROMAN DERIVATIVES
Document Type and Number:
WIPO Patent Application WO/2000/071538
Kind Code:
A2
Abstract:
This invention relates to novel 1-trifluoromethyl-4-hydroxy-7-piperidinyl-aminomethylchroman derivatives of formula (I) wherein R?1¿ is C¿1?-C¿6? alkyl; R?2¿ is hydrogen, C¿1?-C¿6? alkyl, halo C¿1?-C¿6? alkyl or phenyl; R?3¿ is hydrogen or halo; and R?4¿ and R?5¿ are independently hydrogen, C¿1?-C¿6? alkyl or halo C¿1?-C¿6? alkyl, their pharmaceutically acceptable salts, pharmaceutical compositions containing such compounds, and the use of such compounds to treat CNS, gastrointestinal and other disorders.
Inventors:
OBACH RONALD SCOTT (US)
SCULLY DOUGLAS ALAN (US)
SCULLY DOUGLAS ALAN (US)
Application Number:
PCT/IB2000/000493
Publication Date:
November 30, 2000
Filing Date:
April 20, 2000
Export Citation:
Assignee:
PFIZER PROD INC (US)
OBACH RONALD SCOTT (US)
SCULLY DOUGLAS ALAN (US)
OBACH RONALD SCOTT (US)
SCULLY DOUGLAS ALAN (US)
International Classes:
A61K31/33; A61K31/435; A61K31/453; A61P1/00; A61P1/04; A61P1/08; A61P1/14; A61P1/16; A61P3/02; A61P9/10; A61P11/02; A61P11/06; A61P13/00; A61P13/02; A61P13/10; A61P15/08; A61P15/10; A61P17/06; A61P17/16; A61P19/02; A61P25/02; A61P25/04; A61P25/06; A61P25/14; A61P25/16; A61P25/18; A61P25/24; A61P25/28; A61P25/30; A61P27/02; A61P29/00; A61P31/04; A61P37/02; A61P37/08; A61P43/00; C07D211/00; C07D311/00; C07D405/12; A61K; A61P; C07D; (IPC1-7): C07D405/12; A61K31/453; A61P25/28; A61P25/24; A61P25/16
Domestic Patent References:
| WO1997008144A1 | 1997-03-06 | |||
| WO1995006645A1 | 1995-03-09 | |||
| WO1997003066A1 | 1997-01-30 | |||
| WO1999025714A1 | 1999-05-27 |
Foreign References:
| EP0826684A1 | 1998-03-04 | |||
| US5646144A | 1997-07-08 |
Attorney, Agent or Firm:
Spiegel, Allen J. (235 East 42nd Street New York, NY, US)
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Claims:
CLAIMS
| 1. | A compound of the formula (I): and its pharmaceutically acceptable salts, wherein R'is C,Ce alkyl; R is hydrogen, CiCe alkyl, halo CiCe alkyl or phenyl; R3 is hydrogen or halo; and R4 and R5 are independently hydrogen, CiCe alkyl or halo CiCe alkyl. |
| 2. | A compound according to claim 1, wherein R'is C,C3 alkyl; R is hydrogen, CiC3 alkyl, halo C1C3 alkyl or phenyl; R3 is hydrogen or fluorine; and R4 and R5 are independently hydrogen, C1C3 alkyl or halo C1C3 alkyl. |
| 3. | A compound according to claim 2, wherein R'is methyl; R2 is hydrogen, methyl, trifluoromethyl or phenyl; R3 is hydrogen; and R and R are hydrogen. |
| 4. | A compound according to claim 1 which is (2S, 3S)3 (6methoxy4hydroxy 1methyl1trifluoromethylisochroman7yl) methylamino2phenylpiperidine or a pharmaceutically acceptable salt thereof. |
| 5. | A pharmaceutical composition for treating a disorder or condition, for which antagonist activity toward substance P is needed, in a mammal, which comprises an amount of the compound of claim 1, or a pharmaceutically acceptable salt thereof, that is effective in treating such disorder or condition, and a pharmaceutically acceptable carrier. |
| 6. | A pharmaceutical composition for treating a disorder or condition selected from dysthymia, major depressive disorder, pediatric depression, generalized anxiety disorder, obsessivecompulsive disorder, panic disorder, phobias such as social phobia and agoraphobia; post traumatic stress disorder, borderline personality disorder, acute pain, chronic pain, migraine, angiogenesis, sunburn, urinary incontinence, inflammatory disorders such as rheumatoid arthritis, osteoarthritis, psoriasis, asthma and allergic disorders; emesis, including acute, delayed and anticipatory emesis wherein the emetic agent or condition is chemotherapy, radiation, surgery, motion, migraine or any other emetic agent or condition; disorders caused by Helicobacter pylori, cardiovascular disorders, ophthalmic disorders, inflammation of the urinary tract, psychosis, schizophrenia, conduct disorder, disruptive behavior disorder, bipolar disorder, movement disorders such as Tourette's syndrome, akineticrigid syndrome, movement disorders associated with Parkinson's disease, tardive dyskinesia and other dyskinesias; cognitive disorders such as dementias and memory disorders, eating disorders such as anorexia nervosa and bulimia nervosa, attention deficit hyperactivity disorder, chronic fatigue syndrome, premature ejaculation, premenstrual syndrome, premenstrual dysphoric disorder, chemical dependencies and addictions, stress related somatic disorders, neuralgia, peripheral neuropathy, gastroesophageal reflux disease, reflex sympathetic dystrophy such as shoulder/hand syndrome; hypersensitivity disorders such as to poison ivy; fibromyalgia, angina, Reynaud's disease, rheumatic diseases such as fibrositis; eczema, rhinitis, allergies, postherpetia neuralgia, cystitis, inflammatory bowel disease, irritable bowel syndrome, colitis, fibrosing and collagen disorders such as scleroderma and eosinophilic fascioliasis; blood flow disorders due to vasodilatation, and disorders related to immune enhancement or suppression such as systemic lupus erythematosus in a mammal, comprising an amount of the compound of claim 1, or a pharmaceutically acceptable salt thereof, that is effective in treating such disorder or condition, and a pharmaceutically acceptable carrier. |
| 7. | A method of treating a disorder or condition for which antagonist activity toward substance P is needed, in a mammal, which comprises administering to a mammal in need of such prevention or treatment an amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof, that is effective in treating such disorder or condition. |
| 8. | A method of treating a disorder or condition selected dysthymia, major depressive disorder, pediatric depression, generalized anxiety disorder, obsessive compulsive disorder, panic disorder, phobias such as social phobia and agoraphobia; post traumatic stress disorder, borderline personality disorder, acute pain, chronic pain, migraine, angiogenesis, sunburn, urinary incontinence, inflammatory disorders such as rheumatoid arthritis, osteoarthritis, psoriasis, asthma and allergic disorders; emesis, including acute, delayed and anticipatory emesis wherein the emetic agent or condition is chemotherapy, radiation, surgery, motion, migraine or any other emetic agent or condition; disorders caused by Helicobacter pylori, cardiovascular disorders, ophthalmic disorders, inflammation of the urinary tract, psychosis, schizophrenia, conduct disorder, disruptive behavior disorder, bipolar disorder, movement disorders such as Tourette's syndrome, akineticrigid syndrome, movement disorders associated with Parkinson's disease, tardive dyskinesia and other dyskinesias; cognitive disorders such as dementias and memory disorders, eating disorders such as anorexia nervosa and bulimia nervosa, attention deficit hyperactivity disorder, chronic fatigue syndrome, premature ejaculation, premenstrual syndrome, premenstrual dysphoric disorder, chemical dependencies and addictions, stress related somatic disorders, neuralgia, peripheral neuropathy, gastroesophageal reflux disease, reflex sympathetic dystrophy such as shoulder/hand syndrome; hypersensitivity disorders such as to poison ivy; fibromyalgia, angina, Reynaud's disease, rheumatic diseases such as fibrositis; eczema, rhinitis, allergies, postherpetia neuralgia, cystitis, inflammatory bowel disease, irritable bowel syndrome, colitis, fibrosing and collagen disorders such as scieroderma and eosinophilic fascioliasis; blood flow disorders due to vasodilatation, and disorders related to immune enhancement or suppression such as systemic lupus erythematosus in a mammal, comprising administering to a mammal in need of such prevention or treatment an amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof, that is effective in preventing or treating such disorder or condition. |
Description:
INTERNATIONAL SEARCH REPORT Inter ; nal Application No PCT/IB 00/00493 C. (Continuation) DOCUMENTS CONSIDERED TO BE RELEVANT Category Citation of document, with indication, where appropriate, of the relevant passages Relevant to claim No. A US 5 646 144 A (SCHILLING WALTER ET AL) 1,5-8 8 July 1997 (1997-07-08) abstract; claim 1 column 19-column 100 ; examples A WO 97 03066 A (PFIZER PHARMA; PFIZER (US); 1,5-8 WAKABAYASHI HIROAKI (JP); IKUNAKA MASA) 30 January 1997 (1997-01-30) cited in the application abstract; claims; examples P, X WO 99 25714 A (PFIZER PHARMA ; SATAKE KUNIO 1,5-8 (JP); PFIZER (US)) 27 May 1999 (1999-05-27) abstract; claims 1 INTERNATIONAL SEARCH REPORT Inten mal Application No information on patent family members PCT B 00/00493 Patentdocument Publication Patent family Publication cited in search report date member (s) date EP 0826684 A 04-03-1998 AU 696948 B 24-09-1998 AU 5120296 A 16-10-1996 US 5886011 A 23-03-1999 CA 2216701 A 03-10-1996 WO 9630367 A 03-10-1996 WO 9708144 A 06-03-1997 AP 643 A 24-04-1998 AU 702698 B 04-03-1999 AU 5776996 A 19-03-1997 BG 102288 A 30-09-1998 BR 9609989 A 06-07-1999 CA 2227814 A 06-03-1997 CN 1193961 A 23-09-1998 CZ 9800521 A 13-01-1999 EP 0861235 A 02-09-1998 HR 960386 A 30-04-1998 HU 9901159 A 28-07-1999 JP 10510554 T 13-10-1998 NO 980751 A 23-02-1998 NZ 308207 A 28-07-1998 PL 325332 A 20-07-1998 SK 20798 A 10-03-1999 WO 9506645 A 09-03-1995 AU 7655094 A 22-03-1995 EP 0783499 A 16-07-1997 IL 110793 A 24-09-1998 ZA 9406470 A 14-11-1995 US 5646144 A 08-07-1997 US 5541195 A 30-07-1996 AT 120456 T 15-04-1995 AU 660180 B 15-06-1995 AU 2096592 A 04-03-1993 CA 2075684 A 13-02-1993 DE 59201771 D 04-05-1995 DK 532456 T 12-06-1995 EP 0532456 A 17-03-1993 ES 2070617 T 01-06-1995 FI 923575 A 13-02-1993 FI 964117 A 14-10-1996 GR 3015954 T 31-07-1995 HU 67088 A 30-01-1995 IL 102769 A 26-01-1999 JP 7196649 A 01-08-1995 MX 9204627 A 01-04-1993 NO 303448 B 13-07-1998 NO 973117 A 15-02-1993 NZ 243888 A 26-03-1996 RU 2114829 C 10-07-1998 US 5310743 A 10-05-1994 ZA 9206013 A 31-03-1993 WO 9703066 A 30-01-1997 CA 2226292 A 30-01-1997 EP 0840732 A 13-05-1998 JP 11502861 T 09-03-1999 WO 9925714 A 27-05-1999 AU 9454998 A 07-06-1999 EP 1032571 A 06-09-2000 NO 20002544 A 17-07-0200