PH26590A - Quinuclidine therapeutic agents - Google Patents
Quinuclidine therapeutic agents Download PDFInfo
- Publication number
- PH26590A PH26590A PH39579A PH39579A PH26590A PH 26590 A PH26590 A PH 26590A PH 39579 A PH39579 A PH 39579A PH 39579 A PH39579 A PH 39579A PH 26590 A PH26590 A PH 26590A
- Authority
- PH
- Philippines
- Prior art keywords
- cis
- phenyl
- quinuclidine
- compound
- methylamino
- Prior art date
Links
- SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical compound C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 title description 35
- 239000003814 drug Substances 0.000 title description 10
- 229940124597 therapeutic agent Drugs 0.000 title description 5
- -1 2,3-dihydrobenzofuranyl Chemical group 0.000 claims description 131
- 150000001875 compounds Chemical class 0.000 claims description 75
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 36
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 30
- 150000003839 salts Chemical class 0.000 claims description 25
- 125000004432 carbon atom Chemical group C* 0.000 claims description 22
- 150000008584 quinuclidines Chemical class 0.000 claims description 19
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 17
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 125000001544 thienyl group Chemical group 0.000 claims description 13
- 241000124008 Mammalia Species 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 8
- 125000000068 chlorophenyl group Chemical group 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 7
- 208000019695 Migraine disease Diseases 0.000 claims description 7
- 208000015114 central nervous system disease Diseases 0.000 claims description 7
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 7
- 206010027599 migraine Diseases 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- 125000004429 atom Chemical group 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 125000001207 fluorophenyl group Chemical group 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
- 208000025985 Central nervous system inflammatory disease Diseases 0.000 claims description 5
- 206010065390 Inflammatory pain Diseases 0.000 claims description 5
- 125000005037 alkyl phenyl group Chemical group 0.000 claims description 5
- 125000004799 bromophenyl group Chemical group 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 239000000460 chlorine Substances 0.000 claims description 5
- 125000001041 indolyl group Chemical group 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
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- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
- 125000005336 allyloxy group Chemical group 0.000 claims description 3
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- 125000002541 furyl group Chemical group 0.000 claims description 3
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- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 claims description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
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- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
- LOTBYPQQWICYBB-UHFFFAOYSA-N methyl n-hexyl-n-[2-(hexylamino)ethyl]carbamate Chemical compound CCCCCCNCCN(C(=O)OC)CCCCCC LOTBYPQQWICYBB-UHFFFAOYSA-N 0.000 claims 1
- 125000003884 phenylalkyl group Chemical group 0.000 claims 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 99
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
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- 102100024304 Protachykinin-1 Human genes 0.000 description 16
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 16
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- 125000005002 aryl methyl group Chemical group 0.000 description 13
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- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
-
- 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Anesthesiology (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Psychiatry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/US1988/004205 WO1990005525A1 (fr) | 1988-11-23 | 1988-11-23 | Derives de quinuclidine en tant qu'antagonsites de substance p |
Publications (1)
Publication Number | Publication Date |
---|---|
PH26590A true PH26590A (en) | 1992-08-19 |
Family
ID=22209014
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PH39579A PH26590A (en) | 1988-11-23 | 1989-11-23 | Quinuclidine therapeutic agents |
Country Status (29)
Country | Link |
---|---|
US (1) | US5162339A (fr) |
EP (1) | EP0409931B1 (fr) |
JP (1) | JPH0647589B2 (fr) |
KR (1) | KR900701782A (fr) |
CN (1) | CN1026111C (fr) |
AP (1) | AP120A (fr) |
AR (1) | AR246522A1 (fr) |
AT (1) | ATE101608T1 (fr) |
AU (1) | AU617906B2 (fr) |
CA (1) | CA2003441C (fr) |
DD (1) | DD285605A5 (fr) |
DE (1) | DE68913194T2 (fr) |
EG (1) | EG19301A (fr) |
ES (1) | ES2062504T3 (fr) |
FI (1) | FI903656A0 (fr) |
HU (1) | HU900517D0 (fr) |
IE (1) | IE893730L (fr) |
IL (1) | IL92336A0 (fr) |
MA (1) | MA21682A1 (fr) |
MX (1) | MX18467A (fr) |
MY (1) | MY105061A (fr) |
NZ (1) | NZ231461A (fr) |
OA (1) | OA10023A (fr) |
PH (1) | PH26590A (fr) |
PL (1) | PL161864B1 (fr) |
PT (1) | PT92361B (fr) |
WO (2) | WO1990005525A1 (fr) |
YU (1) | YU47097B (fr) |
ZA (1) | ZA898901B (fr) |
Families Citing this family (154)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GR1001124B (el) * | 1989-11-20 | 1993-04-28 | Pfizer | Θεραπευτικοι παραγοντες κουινουκλιδινης. |
UA41251C2 (uk) * | 1990-01-04 | 2001-09-17 | Пфайзер, Інк. | Гідровані азотвмісні гетероциклічні сполуки, похідні піперидину, фармацевтична композиція та спосіб пригнічення активності речовини р в організмі |
US5332817A (en) * | 1990-01-04 | 1994-07-26 | Pfizer Inc. | 3-aminopiperidine derivatives and related nitrogen containing heterocycles |
US5232929A (en) * | 1990-11-28 | 1993-08-03 | Pfizer Inc. | 3-aminopiperidine derivatives and related nitrogen containing heterocycles and pharmaceutical compositions and use |
US5364943A (en) * | 1991-11-27 | 1994-11-15 | Pfizer Inc. | Preparation of substituted piperidines |
ATE113947T1 (de) * | 1990-06-01 | 1994-11-15 | Pfizer | 3-amino-2-arylchinuclidine, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische zubereitungen. |
EP0540526B1 (fr) * | 1990-07-23 | 1994-12-28 | Pfizer Inc. | Derives de quinuclidine |
EP0550635B1 (fr) * | 1990-09-28 | 1995-04-19 | Pfizer Inc. | Analogues cycliques d'heterocycles non aromatiques contenant de l'azote |
US5138060A (en) * | 1991-01-03 | 1992-08-11 | Pfizer Inc. | Process and intermediates for preparing azabicyclo(2.2.2)octan-3-imines |
US5216163A (en) * | 1991-01-03 | 1993-06-01 | Pfizer Inc | Process for preparing azabicyclo[2.2.2]octan-3-imines |
HUT65612A (en) * | 1991-01-10 | 1994-07-28 | Pfizer | Process n-alcyl-quinuclidinium salts of p-antagonistic activity |
DE69220258T2 (de) * | 1991-02-11 | 1997-12-18 | Merck Sharp & Dohme | Azabicyclische Verbindungen, diese enthaltende pharmazeutische Zubereitungen und ihre therapeutische Verwendung |
ES2065175T3 (es) * | 1991-03-01 | 1995-02-01 | Pfizer | Derivados de 1-azabiciclo(3.2.2)nonan-3-amina. |
BR9205807A (pt) * | 1991-03-26 | 1994-06-28 | Pfizer | Preparação estéreo-seletiva de piperidinas substituidas |
FR2676442B1 (fr) * | 1991-05-17 | 1993-08-06 | Rhone Poulenc Rorer Sa | Nouveau derives de perhydroisoindole, leur preparation et les compositions pharmaceutiques qui les contiennent. |
US5716965A (en) * | 1991-05-22 | 1998-02-10 | Pfizer Inc. | Substituted 3-aminoquinuclidines |
WO1992020661A1 (fr) * | 1991-05-22 | 1992-11-26 | Merck & Co., Inc. | N, n-diacylpiperazines |
HUT65771A (en) * | 1991-05-22 | 1994-07-28 | Pfizer | Process for producing substituted 3-amino-quinuclidine derivatives and pharmaceutical compositions containing them |
UA27776C2 (uk) * | 1991-05-31 | 2000-10-16 | Пфайзер Інк. | Похідні хінуклідину та їх фармацевтично прийнятні солі, що є антагоністами речовини р у ссавців, фармацевтична композиція, що має антагоністичну дію на речовину р у ссавців |
KR0154882B1 (ko) * | 1991-06-20 | 1998-11-16 | 알렌 제이. 스피겔 | 질소 함유 헤테로사이클릭 화합물의 플루오로알콕시벤질아미노 유도체 |
TW202432B (fr) * | 1991-06-21 | 1993-03-21 | Pfizer | |
US5288730A (en) * | 1991-06-24 | 1994-02-22 | Merck Sharp & Dohme Limited | Azabicyclic compounds, pharmaceutical compositions containing them and their use in therapy |
EP0536817A1 (fr) * | 1991-07-05 | 1993-04-14 | MERCK SHARP & DOHME LTD. | Composés azabicycliques comme antagonistes des tachykinines |
MY110227A (en) * | 1991-08-12 | 1998-03-31 | Ciba Geigy Ag | 1-acylpiperindine compounds. |
EP0600952B1 (fr) * | 1991-08-20 | 1996-04-17 | MERCK SHARP & DOHME LTD. | Composes azacycliques, procedes de preparation et compositions pharmaceutiques les contenant |
EP1082959A1 (fr) * | 1991-09-20 | 2001-03-14 | Glaxo Group Limited | Utilisation des NK1-antagonistes pour le traitement de la depression |
US5527808A (en) * | 1991-09-26 | 1996-06-18 | Pfizer Inc. | Fused tricyclic nitrogen containing heterocycles |
WO1993009116A1 (fr) * | 1991-11-07 | 1993-05-13 | Yoshitomi Pharmaceutical Industries, Ltd. | Compose a base de quinuclidine et utilisation dudit compose en medecine |
DK0613458T3 (da) * | 1991-11-12 | 1998-02-09 | Pfizer | Acykliske ethylendiaminderivater som substans P receptorantagonister |
FR2688219B1 (fr) | 1992-03-03 | 1994-07-08 | Sanofi Elf | Sels d'ammonium quaternaires de composes aromatiques amines, leur preparation et compositions pharmaceutiques les contenant. |
JP2656702B2 (ja) * | 1992-03-23 | 1997-09-24 | ファイザー製薬株式会社 | ペプチド性キヌクリジン |
WO1993021181A1 (fr) * | 1992-04-15 | 1993-10-28 | Merck Sharp & Dohme Limited | Composes azacycliques |
US5444074A (en) * | 1992-04-15 | 1995-08-22 | Merck Sharp & Dohme Limited | Piperidine tachykinin receptor antagonists |
CA2134964C (fr) * | 1992-05-18 | 1997-12-30 | Manoj C. Desai | Derives aza-bicycliques pontes, utilises comme antagonistes de la substance p |
US5637699A (en) * | 1992-06-29 | 1997-06-10 | Merck & Co., Inc. | Process for preparing morpholine tachykinin receptor antagonists |
US5719147A (en) * | 1992-06-29 | 1998-02-17 | Merck & Co., Inc. | Morpholine and thiomorpholine tachykinin receptor antagonists |
US6048859A (en) | 1992-06-29 | 2000-04-11 | Merck & Co., Inc. | Morpholine and thiomorpholine tachykinin receptor antagonists |
JP2683783B2 (ja) * | 1992-07-10 | 1997-12-03 | 雪印乳業株式会社 | シェーグレン症候群治療剤 |
GB9216911D0 (en) * | 1992-08-10 | 1992-09-23 | Merck Sharp & Dohme | Therapeutic agents |
US5721255A (en) * | 1992-08-19 | 1998-02-24 | Pfizer Inc. | Substituted benzylamino nitrogen containing non-aromatic heterocycles |
US5387595A (en) * | 1992-08-26 | 1995-02-07 | Merck & Co., Inc. | Alicyclic compounds as tachykinin receptor antagonists |
FR2695641B1 (fr) * | 1992-09-11 | 1994-11-25 | Rhone Poulenc Rorer Sa | (Amino-3 phényl)-1 éthanesulfonate d'hydroquinine optiquement actif, sa préparation et son utilisation. |
JP2656699B2 (ja) * | 1992-10-21 | 1997-09-24 | ファイザー製薬株式会社 | 置換ベンジルアミノキヌクリジン |
US5604241A (en) * | 1992-10-21 | 1997-02-18 | Pfizer Inc. | Substituted benzylaminoquinuclidines as substance P antagonists |
US5837711A (en) * | 1992-10-28 | 1998-11-17 | Pfizer Inc. | Substituted quinuclidines as substance P antagonists |
JP2656700B2 (ja) * | 1992-10-28 | 1997-09-24 | ファイザー製薬株式会社 | 置換キヌクリジン誘導体 |
ES2096312T3 (es) * | 1992-11-12 | 1997-03-01 | Pfizer | Derivado de quinuclidina como antagonista de la sustancia p. |
US5344830A (en) * | 1992-12-10 | 1994-09-06 | Merck & Co., Inc. | N,N-diacylpiperazine tachykinin antagonists |
WO1994013663A1 (fr) * | 1992-12-10 | 1994-06-23 | Pfizer Inc. | Heterocycles non aromatiques substitues par aminomethylene et leur utilisation comme antagonistes de substance p |
US5830854A (en) * | 1992-12-14 | 1998-11-03 | Merck Sharp & Dohme, Limited | Method of treating cystic fibrosis using a tachykinin receptor antagonist |
ATE166650T1 (de) * | 1993-03-04 | 1998-06-15 | Pfizer | Spiroazacyclischderivate als substanz p antagonisten |
US5496833A (en) * | 1993-04-13 | 1996-03-05 | Merck Sharp & Dohme Limited | Piperidine tachykinin receptor antagonists |
IL109646A0 (en) * | 1993-05-19 | 1994-08-26 | Pfizer | Heteroatom substituted alkyl benzylamino-quinuclidines |
JP2822274B2 (ja) * | 1993-05-19 | 1998-11-11 | ファイザー製薬株式会社 | P物質拮抗剤としてのヘテロ原子置換アルキルベンジルアミノキヌクリジン類 |
US5393762A (en) * | 1993-06-04 | 1995-02-28 | Pfizer Inc. | Pharmaceutical agents for treatment of emesis |
US5348955A (en) * | 1993-06-22 | 1994-09-20 | Merck & Co., Inc. | N,N-diacylpiperazines |
ES2121213T3 (es) * | 1993-07-15 | 1998-11-16 | Pfizer | Benciloxiquinuclidinas como antagonistas de la sustancia p. |
US5854262A (en) * | 1993-10-07 | 1998-12-29 | Pfizer Inc. | Aminomethylene substituted non-aromatic heterocycles and use as substance P antagonists |
US5922878A (en) * | 1994-03-03 | 1999-07-13 | Boehringer Ingelheim Gmbh | Amino acid derivatives, processes for preparing them and pharmaceutical compositions containing these compounds |
PE45195A1 (es) * | 1994-03-03 | 1996-01-17 | Boehringer Ingelheim Kg | Derivado de aminoacido, procedimiento para su preparacion y composicion farmaceutica que lo contiene |
IL112778A0 (en) * | 1994-03-04 | 1995-05-26 | Merck & Co Inc | Substituted heterocycles, their preparation and pharmaceutical compositions containing them |
US6203803B1 (en) | 1994-12-14 | 2001-03-20 | Societe L'oreal S.A. | Use of a substance P antagonist in a cosmetic composition, and the composition thus obtained |
FR2719474B1 (fr) * | 1994-05-05 | 1996-05-31 | Oreal | Utilisation d'un antagoniste de substance P dans une composition cosmétique et composition obtenue. |
FR2719476B1 (fr) * | 1994-05-05 | 1997-05-23 | Oreal | Utilisation d'un antagoniste de substance P dans une composition cosmétique et composition obtenue. |
TW397825B (en) * | 1994-10-14 | 2000-07-11 | Novartis Ag | Aroyl-piperidine derivatives |
FR2725900B1 (fr) * | 1994-10-21 | 1997-07-18 | Sanofi Sa | Utilisation d'antagonistes des recepteurs nk1 pour la preparation de medicaments a action cardioregulatrice |
IL116249A (en) * | 1994-12-12 | 2003-07-06 | Pfizer | Nk-1 receptor antagonists for the treatment of neuronal damage and stroke |
FR2728169A1 (fr) | 1994-12-19 | 1996-06-21 | Oreal | Utilisation d'un antagoniste de substance p pour le traitement des prurits et des dysesthesies oculaires ou palpebrales |
FR2728166A1 (fr) | 1994-12-19 | 1996-06-21 | Oreal | Composition topique contenant un antagoniste de substance p |
FR2728165A1 (fr) | 1994-12-19 | 1996-06-21 | Oreal | Utilisation d'un antagoniste de substance p pour le traitement des rougeurs cutanees d'origine neurogene |
FR2729954B1 (fr) | 1995-01-30 | 1997-08-01 | Sanofi Sa | Composes heterocycliques substitues, procede pour leur preparation et compositions pharmaceutiques les contenant |
JP3042894B2 (ja) | 1995-07-07 | 2000-05-22 | ファイザー製薬株式会社 | サブスタンスpアンタゴニストとしての置換ベンゾラクタム化合物 |
US6288225B1 (en) | 1996-05-09 | 2001-09-11 | Pfizer Inc | Substituted benzolactam compounds as substance P antagonists |
PE8798A1 (es) * | 1995-07-17 | 1998-03-02 | Pfizer | Procedimiento de separacion de los enantiomeros del 1-azabiciclo[2.2.2] octan-3-amina, 2-(difenilmetil) -n- [[2-metoxi-5-(1-metiletil) fenil] metil] |
TW458774B (en) | 1995-10-20 | 2001-10-11 | Pfizer | Antiemetic pharmaceutical compositions |
FR2741262B1 (fr) | 1995-11-20 | 1999-03-05 | Oreal | Utilisation d'un antagoniste de tnf-alpha pour le traitement des rougeurs cutanees d'origine neurogene |
MX9706944A (es) * | 1996-09-12 | 1998-08-30 | Pfizer | Quinuclidinas sustituidas con tetrazolilo como antagonistas de la sustancia p. |
US6117855A (en) | 1996-10-07 | 2000-09-12 | Merck Sharp & Dohme Ltd. | Use of a NK-1 receptor antagonist and an antidepressant and/or an anti-anxiety agent |
US6613765B1 (en) | 1996-12-02 | 2003-09-02 | Merck Sharp & Dohme Limited | Use of NK-1 receptor antagonists for treating major depressive disorders |
US6114315A (en) * | 1996-12-02 | 2000-09-05 | Merck Sharp & Dohme Ltd. | Use of NK-1 receptor antagonists for treating major depressive disorders with anxiety |
US6100256A (en) * | 1996-12-02 | 2000-08-08 | Merck Sharp & Dohme Ltd. | Use of NK-1 receptors antagonists for treating schizophrenic disorders |
US5977104A (en) * | 1996-12-02 | 1999-11-02 | Merck Sharp & Dohme Ltd. | Use of NK-1 receptor antagonists for treating bipolar disorders |
JP2001504851A (ja) * | 1996-12-02 | 2001-04-10 | メルク シヤープ エンド ドーム リミテツド | 性的機能不全の治療のためのnk−1受容体拮抗薬の使用 |
CA2273853A1 (fr) * | 1996-12-02 | 1998-06-11 | Merck Sharp & Dohme Limited | Utilisation d'antagonistes du recepteur nk-1 en traitement de troubles cognitifs |
CA2273856A1 (fr) * | 1996-12-02 | 1998-06-11 | Merck Sharp & Dohme Limited | Utilisation d'antagonistes du recepteur nk-1 dans le traitement des troubles bipolaires |
JP2001507678A (ja) * | 1996-12-02 | 2001-06-12 | メルク シヤープ エンド ドーム リミテツド | 運動障害の治療のためのnk−1受容体拮抗薬の使用 |
JP2001504853A (ja) * | 1996-12-02 | 2001-04-10 | メルク シヤープ エンド ドーム リミテツド | 物質使用障害の治療のためのnk−1受容体拮抗薬の使用 |
GB9716463D0 (en) * | 1997-08-04 | 1997-10-08 | Merck Sharp & Dohme | Therapeutic agents |
US6087348A (en) * | 1997-12-01 | 2000-07-11 | Merck Sharp & Dohme Ltd. | Use of NK-1 receptor antagonists for treating stress disorders |
US6271230B1 (en) | 1997-12-01 | 2001-08-07 | Merck Sharp & Dohme Limited | Use of NK-1 receptor antagonists for treating cognitive disorders |
US6156749A (en) * | 1997-12-01 | 2000-12-05 | Merck Sharp & Dohme Limited | Use of NK-1 receptor antagonists for treating movement disorders |
ATE238044T1 (de) * | 1998-08-25 | 2003-05-15 | Novartis Pharma Gmbh | Verwendung von substanz p antagonisten zur behandlung des chronischen ermüdungssyndroms und/oder der fibromyalgie |
US6387925B1 (en) * | 1999-06-01 | 2002-05-14 | Pfizer Inc. | Polymorphs of a crystalline azo-bicyclo (2.2.2) oct-3-yl amine citrate and their pharmaceutical compositions |
US6262067B1 (en) * | 1999-06-22 | 2001-07-17 | Pfizer Inc. | Polymorphs of a crystalline azo-bicyclo 2,2,2 OCT-3-yl amine dihydrochloride and their pharmaceutical compositions |
CA2324116A1 (fr) * | 1999-10-25 | 2001-04-25 | Susan Beth Sobolov-Jaynes | Antagonistes du recepteur nk-1 et eletriptan pour le traitement de la migraine |
RU2309953C2 (ru) | 1999-11-03 | 2007-11-10 | Эймр Текнолоджи, Инк. | Арил- и гетероарилзамещенные тетрагидроизохинолины, фармацевтическая композиция и способ лечения на их основе |
US7163949B1 (en) | 1999-11-03 | 2007-01-16 | Amr Technology, Inc. | 4-phenyl substituted tetrahydroisoquinolines and use thereof |
USRE44578E1 (en) | 2000-04-10 | 2013-11-05 | Teva Pharmaceutical Industries, Ltd. | Stable pharmaceutical compositions containing 7-substituted-3,5-dihydroxyheptanoic acids or 7-substituted-3,5-dihydroxyheptenoic acids |
IL142810A0 (en) * | 2000-05-03 | 2002-03-10 | Pfizer Prod Inc | Pharmaceutical uses for fluoroalkoxybenzylamino derivatives of nitrogen containing heterocycles |
KR100821410B1 (ko) | 2000-07-11 | 2008-04-10 | 에이엠알 테크놀로지, 인크. | 4-페닐 치환된 테트라하이드로이소퀴놀린 및 이의치료학적 용도 |
US20020049211A1 (en) * | 2000-09-06 | 2002-04-25 | Sobolov-Jaynes Susan Beth | Combination treatment for depression and anxiety |
EP1192952A3 (fr) * | 2000-09-28 | 2003-03-26 | Pfizer Products Inc. | Composition pour le traitement de la dépression et de l'anxieté contenant un antagoniste du recepteur NK-3 et un antagoniste du récepteur NK-1 |
PL367944A1 (en) * | 2001-07-20 | 2005-03-07 | Pfizer Products Inc. | Use of nk-1 receptor antagonists to modify unwanted behavior in dogs, cats and horses |
US6861526B2 (en) * | 2002-10-16 | 2005-03-01 | Pfizer Inc. | Process for the preparation of (S,S)-cis-2-benzhydryl-3-benzylaminoquinuclidine |
WO2004067703A2 (fr) * | 2003-01-31 | 2004-08-12 | Pfizer Products Inc. | Antagonistes 5ht7 et agonistes inverses |
US20050136487A1 (en) * | 2003-10-27 | 2005-06-23 | Meyer Donald W. | Transmissible spongiform encephalopathy detection in cervids, sheep and goats |
WO2005051919A1 (fr) * | 2003-11-26 | 2005-06-09 | Pfizer Products Inc. | Derives d'aminopyrazole en tant qu'inhibiteurs de la gsk-3 |
ZA200701232B (en) | 2004-07-15 | 2008-08-27 | Amr Technology Inc | Aryl-and heteroaryl-substituted tetrahydroisoquinolines and use thereof to block reuptake of norepinephrine, dopamine and serotonin |
ES2382814T3 (es) | 2005-05-17 | 2012-06-13 | Merck Sharp & Dohme Ltd. | Ácido cis-4-[(4-clorofenil)sulfonil]-4-(2,5-difluorofenil)ciclohexanopropanoico para el tratamiento del cáncer |
EP1904069B1 (fr) | 2005-07-15 | 2018-06-13 | Albany Molecular Research, Inc. | Tetrahydrobenzazepines substituees par aryle et heteroaryle, et leur utilisation pour bloquer la reabsorption de la noradrenaline, de la dopamine, et de la serotonine |
US8293900B2 (en) | 2005-09-29 | 2012-10-23 | Merck Sharp & Dohme Corp | Acylated spiropiperidine derivatives as melanocortin-4 receptor modulators |
GB0603041D0 (en) | 2006-02-15 | 2006-03-29 | Angeletti P Ist Richerche Bio | Therapeutic compounds |
CA2664113C (fr) | 2006-09-22 | 2013-05-28 | Merck & Co., Inc. | Utilisation de la platencine et de la platensimycine en tant qu'inhibiteurs de la synthese des acides gras pour traiter l'obesite, lediabete et le cancer |
US20110218176A1 (en) | 2006-11-01 | 2011-09-08 | Barbara Brooke Jennings-Spring | Compounds, methods, and treatments for abnormal signaling pathways for prenatal and postnatal development |
BRPI0806245B1 (pt) | 2007-01-10 | 2022-01-25 | Msd Italia S.R.L. | Compostos de fórmula i e seus usos |
KR20090112722A (ko) | 2007-01-24 | 2009-10-28 | 글락소 그룹 리미티드 | 3,5-디아미노-6-(2,3-디클로로페닐)-1,2,4-트리아진 또는 r(-)-2,4-디아미노-5-(2,3-디클로로페닐)-6-플루오로메틸 피리미딘 및 nk1을 포함하는 제약 조성물 |
CA2682727C (fr) | 2007-04-02 | 2016-03-22 | Banyu Pharmaceutical Co., Ltd. | Derive d'indoledione |
EP2170076B1 (fr) | 2007-06-27 | 2016-05-18 | Merck Sharp & Dohme Corp. | Dérivés de 4-carboxybenzylamino utilisés en tant qu'inhibiteurs de l'histone désacétylase |
US8598184B2 (en) | 2008-03-03 | 2013-12-03 | Tiger Pharmatech | Protein kinase inhibitors |
US9156812B2 (en) | 2008-06-04 | 2015-10-13 | Bristol-Myers Squibb Company | Crystalline form of 6-[(4S)-2-methyl-4-(2-naphthyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]pyridazin-3-amine |
AR071997A1 (es) | 2008-06-04 | 2010-07-28 | Bristol Myers Squibb Co | Forma cristalina de 6-((4s)-2-metil-4-(2-naftil)-1,2,3,4-tetrahidroisoquinolin-7-il)piridazin-3-amina |
UA105182C2 (ru) | 2008-07-03 | 2014-04-25 | Ньюрексон, Інк. | Бензоксазины, бензотиазины и родственные соединения, которые имеют ингибирующую nos активность |
MX2011004551A (es) | 2008-10-30 | 2011-05-25 | Merck Sharp & Dohme | Antagonistas del receptor de orexina de isonicotinamida. |
TW201031664A (en) * | 2009-01-26 | 2010-09-01 | Targacept Inc | Preparation and therapeutic applications of (2S,3R)-N-2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)-3,5-difluorobenzamide |
US8691825B2 (en) | 2009-04-01 | 2014-04-08 | Merck Sharp & Dohme Corp. | Inhibitors of AKT activity |
KR20120034644A (ko) | 2009-05-12 | 2012-04-12 | 알바니 몰레큘라 리써치, 인크. | 아릴, 헤테로아릴, 및 헤테로사이클 치환된 테트라하이드로이소퀴놀린 및 이의 용도 |
CN102638982B (zh) | 2009-05-12 | 2015-07-08 | 百时美施贵宝公司 | (S)-7-([1,2,4]三唑并[1,5-a]吡啶-6-基)-4-(3,4-二氯苯基)-1,2,3,4-四氢异喹啉的晶型及其用途 |
CA2760837C (fr) | 2009-05-12 | 2018-04-03 | Albany Molecular Research, Inc. | 7-([1,2,4]triazolo[1,5-.alpha.]pyridin-6-yl)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydroisoquinoline et son utilisation |
WO2011046771A1 (fr) | 2009-10-14 | 2011-04-21 | Schering Corporation | Pipéridines substituées qui accroissent l'activité de p53, et utilisations de ces composés |
WO2011163330A1 (fr) | 2010-06-24 | 2011-12-29 | Merck Sharp & Dohme Corp. | Nouveaux composés hétérocycliques utilisés comme inhibiteurs de erk |
CA2805265A1 (fr) | 2010-08-02 | 2012-02-09 | Merck Sharp & Dohme Corp. | Inhibition a mediation par interference arn de catenine (proteine associee a cadherine), expression du gene beta 1 (ctnnb1) a l'aide de petit acide nucleique interferent (sian) |
WO2012024170A2 (fr) | 2010-08-17 | 2012-02-23 | Merck Sharp & Dohme Corp. | Inhibition médiée par des arn interférents de l'expression génique du virus de l'hépatite b (vhb) à l'aide de petits acides nucléiques interférents (pani) |
US8883801B2 (en) | 2010-08-23 | 2014-11-11 | Merck Sharp & Dohme Corp. | Substituted pyrazolo[1,5-a]pyrimidines as mTOR inhibitors |
US8946216B2 (en) | 2010-09-01 | 2015-02-03 | Merck Sharp & Dohme Corp. | Indazole derivatives useful as ERK inhibitors |
EP2615916B1 (fr) | 2010-09-16 | 2017-01-04 | Merck Sharp & Dohme Corp. | Dérivés condensés de pyrazole utilisés comme nouveaux inhibiteurs erk |
WO2012058210A1 (fr) | 2010-10-29 | 2012-05-03 | Merck Sharp & Dohme Corp. | INHIBITION FACILITÉE PAR L'INTERFÉRENCE D'ARN DE L'EXPRESSION D'UN GÈNE AU MOYEN D'ACIDES NUCLÉIQUES INTERFÉRENTS COURTS (siNA) |
WO2012087772A1 (fr) | 2010-12-21 | 2012-06-28 | Schering Corporation | Dérivés d'indazole utiles en tant qu'inhibiteurs de erk |
JP2014514321A (ja) | 2011-04-21 | 2014-06-19 | メルク・シャープ・アンド・ドーム・コーポレーション | インスリン様増殖因子1受容体阻害剤 |
AR088352A1 (es) | 2011-10-19 | 2014-05-28 | Merck Sharp & Dohme | Antagonistas del receptor de 2-piridiloxi-4-nitrilo orexina |
US9023865B2 (en) | 2011-10-27 | 2015-05-05 | Merck Sharp & Dohme Corp. | Compounds that are ERK inhibitors |
US20150299696A1 (en) | 2012-05-02 | 2015-10-22 | Sirna Therapeutics, Inc. | SHORT INTERFERING NUCLEIC ACID (siNA) COMPOSITIONS |
WO2014052563A2 (fr) | 2012-09-28 | 2014-04-03 | Merck Sharp & Dohme Corp. | Nouveaux composés inhibiteurs de erk |
US10154988B2 (en) | 2012-11-14 | 2018-12-18 | The Johns Hopkins University | Methods and compositions for treating schizophrenia |
MX363243B (es) | 2012-11-28 | 2019-03-14 | Merck Sharp & Dohme | Composiciones para tratar cáncer y usos de dichas composiciones. |
RU2690663C2 (ru) | 2012-12-20 | 2019-06-05 | Мерк Шарп И Доум Корп. | Замещенные имидазопиридины в качестве ингибиторов hdm2 |
US9540377B2 (en) | 2013-01-30 | 2017-01-10 | Merck Sharp & Dohme Corp. | 2,6,7,8 substituted purines as HDM2 inhibitors |
US20160194368A1 (en) | 2013-09-03 | 2016-07-07 | Moderna Therapeutics, Inc. | Circular polynucleotides |
NL2015865B1 (en) | 2015-11-27 | 2017-06-13 | Le Vet B V | Maropitant Formulation. |
US10947234B2 (en) | 2017-11-08 | 2021-03-16 | Merck Sharp & Dohme Corp. | PRMT5 inhibitors |
WO2020033284A1 (fr) | 2018-08-07 | 2020-02-13 | Merck Sharp & Dohme Corp. | Inhibiteurs de prmt5 |
EP3833668A4 (fr) | 2018-08-07 | 2022-05-11 | Merck Sharp & Dohme Corp. | Inhibiteurs de prmt5 |
US11098029B2 (en) | 2019-02-13 | 2021-08-24 | Merck Sharp & Dohme Corp. | 5-alkyl pyrrolidine orexin receptor agonists |
EP4010314B1 (fr) | 2019-08-08 | 2024-02-28 | Merck Sharp & Dohme LLC | Agonistes du récepteur de l'orexine de type pyrrolidine et pipéridine hétéroaryle |
AU2021329805B2 (en) | 2020-08-18 | 2024-02-29 | Merck Sharp & Dohme Llc | Bicycloheptane pyrrolidine orexin receptor agonists |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3534053A (en) * | 1967-05-24 | 1970-10-13 | American Home Prod | Quinuclidine derivatives |
US3506673A (en) * | 1968-03-29 | 1970-04-14 | Aldrich Chem Co Inc | 2-(4'halo)-benzhydryl-3-quinuclidinols |
US3506672A (en) * | 1968-03-29 | 1970-04-14 | Aldrich Chem Co Inc | 2-(4,4'-dihalo)-benzhydryl-3-quinuclidinols |
US3560510A (en) * | 1969-03-05 | 1971-02-02 | Aldrich Chem Co Inc | 2-benzhydrylquinuclidines |
US3917612A (en) * | 1971-07-27 | 1975-11-04 | Hoffmann La Roche | 1,1-Dichloro-3-(4-piperidinyl)propan-2-ols |
BE789679A (fr) * | 1971-10-05 | 1973-04-04 | Leo Pharm Prod Ltd | Nouveaux derives d'acide amino-5 isophtalique et leurs procedesde preparation |
US3933906A (en) * | 1972-10-13 | 1976-01-20 | Ciba-Geigy Corporation | 3,4-Bisamino-5-sulfamoylbenzoic acids |
FR2529548A1 (fr) * | 1982-07-02 | 1984-01-06 | Delalande Sa | Nouveaux derives de l'amino-3 quinuclidine, leur procede et leur application en therapeutique |
EP0272052B1 (fr) * | 1986-12-16 | 1992-07-08 | A.H. ROBINS COMPANY, INCORPORATED (a Delaware corporation) | N-(1-Azabicyclo[2.2.2]oct-3-yl)benzamides et -thiobenzamides anxiolytiques |
EP0289170B1 (fr) * | 1987-04-25 | 1993-06-23 | Beecham Group Plc | Composés azabicycliques, leur procédé de préparation et compositions pharmaceutiques les contenant |
-
1988
- 1988-11-23 MX MX1846789A patent/MX18467A/es unknown
- 1988-11-23 WO PCT/US1988/004205 patent/WO1990005525A1/fr unknown
-
1989
- 1989-11-16 IL IL92336A patent/IL92336A0/xx unknown
- 1989-11-20 ES ES90901247T patent/ES2062504T3/es not_active Expired - Lifetime
- 1989-11-20 EP EP90901247A patent/EP0409931B1/fr not_active Expired - Lifetime
- 1989-11-20 US US07/566,338 patent/US5162339A/en not_active Expired - Lifetime
- 1989-11-20 AU AU46619/89A patent/AU617906B2/en not_active Ceased
- 1989-11-20 DE DE68913194T patent/DE68913194T2/de not_active Expired - Fee Related
- 1989-11-20 HU HU90517A patent/HU900517D0/hu not_active IP Right Cessation
- 1989-11-20 KR KR1019900701573A patent/KR900701782A/ko not_active Application Discontinuation
- 1989-11-20 WO PCT/US1989/005338 patent/WO1990005729A1/fr active IP Right Grant
- 1989-11-20 JP JP2501319A patent/JPH0647589B2/ja not_active Expired - Fee Related
- 1989-11-21 NZ NZ231461A patent/NZ231461A/xx unknown
- 1989-11-21 MY MYPI89001617A patent/MY105061A/en unknown
- 1989-11-21 CA CA002003441A patent/CA2003441C/fr not_active Expired - Fee Related
- 1989-11-21 PT PT92361A patent/PT92361B/pt not_active IP Right Cessation
- 1989-11-22 AP APAP/P/1989/000152A patent/AP120A/en active
- 1989-11-22 CN CN89109556A patent/CN1026111C/zh not_active Expired - Fee Related
- 1989-11-22 IE IE893730A patent/IE893730L/xx unknown
- 1989-11-22 MA MA21938A patent/MA21682A1/fr unknown
- 1989-11-22 YU YU222289A patent/YU47097B/sh unknown
- 1989-11-22 ZA ZA898901A patent/ZA898901B/xx unknown
- 1989-11-22 AR AR89315505A patent/AR246522A1/es active
- 1989-11-23 EG EG57889A patent/EG19301A/xx active
- 1989-11-23 PL PL89282431A patent/PL161864B1/pl unknown
- 1989-11-23 DD DD89334812A patent/DD285605A5/de not_active IP Right Cessation
- 1989-11-23 PH PH39579A patent/PH26590A/en unknown
-
1990
- 1990-06-08 AT AT90901247T patent/ATE101608T1/de not_active IP Right Cessation
- 1990-07-19 FI FI903656A patent/FI903656A0/fi not_active IP Right Cessation
- 1990-07-20 OA OA59821A patent/OA10023A/en unknown
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