UA80584C2 - Заміщені похідні 1-піперидин-4-іл-4-піролідин-3-ілпіперазину та їх застосування як антагоністів нейрокінінів - Google Patents

Заміщені похідні 1-піперидин-4-іл-4-піролідин-3-ілпіперазину та їх застосування як антагоністів нейрокінінів Download PDF

Info

Publication number: UA80584C2
Authority: UA; Ukraine
Prior art keywords: alkyl; group; compound; amino; mono
Prior art date: 2002-12-23

Application number

UAA200505412A

Other languages

English (en)

Russian (ru)

Ukrainian (uk)

Inventor

Франс Едуард Янссенс

Франсуа Марія Соммен

Бек Бенуа Крістіан Альберт Хіслен де

Йозеф Елізабет Леенартс

Original Assignee

Янссен Фармацевтика Н.В.

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.)

2002-12-23

Filing date

2003-12-17

Publication date

2007-10-10

2003-12-17 Application filed by Янссен Фармацевтика Н.В. filed Critical Янссен Фармацевтика Н.В.

2007-10-10 Publication of UA80584C2 publication Critical patent/UA80584C2/uk

Links

239000005557 antagonist Substances 0.000 title description 31
QUVPEYUQPVHCPV-UHFFFAOYSA-N 1-piperidin-4-yl-4-pyrrolidin-3-ylpiperazine Chemical class C1NCCC1N1CCN(C2CCNCC2)CC1 QUVPEYUQPVHCPV-UHFFFAOYSA-N 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 280
238000002360 preparation method Methods 0.000 claims abstract description 50
238000011282 treatment Methods 0.000 claims abstract description 43
206010047700 Vomiting Diseases 0.000 claims abstract description 37
150000003839 salts Chemical class 0.000 claims abstract description 34
239000002253 acid Substances 0.000 claims abstract description 28
229940002612 prodrug Drugs 0.000 claims abstract description 22
239000000651 prodrug Substances 0.000 claims abstract description 22
208000019901 Anxiety disease Diseases 0.000 claims abstract description 20
239000003814 drug Substances 0.000 claims abstract description 16
230000036506 anxiety Effects 0.000 claims abstract description 13
201000000980 schizophrenia Diseases 0.000 claims abstract description 10
-1 cyano, hydroxy, formyl Chemical group 0.000 claims description 91
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 37
125000000217 alkyl group Chemical group 0.000 claims description 32
208000035475 disorder Diseases 0.000 claims description 31
229910052736 halogen Inorganic materials 0.000 claims description 29
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 29
125000004432 carbon atom Chemical group C* 0.000 claims description 28
150000002367 halogens Chemical class 0.000 claims description 27
230000008673 vomiting Effects 0.000 claims description 27
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
238000000034 method Methods 0.000 claims description 23
125000003545 alkoxy group Chemical group 0.000 claims description 19
229930195734 saturated hydrocarbon Natural products 0.000 claims description 18
208000002193 Pain Diseases 0.000 claims description 17
208000002551 irritable bowel syndrome Diseases 0.000 claims description 17
229910052739 hydrogen Inorganic materials 0.000 claims description 16
230000036407 pain Effects 0.000 claims description 16
125000004122 cyclic group Chemical group 0.000 claims description 14
229940079593 drug Drugs 0.000 claims description 14
102000003141 Tachykinin Human genes 0.000 claims description 13
125000004076 pyridyl group Chemical group 0.000 claims description 13
125000001424 substituent group Chemical group 0.000 claims description 13
108060008037 tachykinin Proteins 0.000 claims description 13
239000001257 hydrogen Substances 0.000 claims description 12
229910052709 silver Inorganic materials 0.000 claims description 12
210000003169 central nervous system Anatomy 0.000 claims description 11
125000004043 oxo group Chemical group O=* 0.000 claims description 10
125000004093 cyano group Chemical group *C#N 0.000 claims description 9
230000003993 interaction Effects 0.000 claims description 9
HGUFODBRKLSHSI-UHFFFAOYSA-N 2,3,7,8-tetrachloro-dibenzo-p-dioxin Chemical compound O1C2=CC(Cl)=C(Cl)C=C2OC2=C1C=C(Cl)C(Cl)=C2 HGUFODBRKLSHSI-UHFFFAOYSA-N 0.000 claims description 8
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 8
230000001404 mediated effect Effects 0.000 claims description 8
125000001624 naphthyl group Chemical group 0.000 claims description 8
125000000168 pyrrolyl group Chemical group 0.000 claims description 8
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 8
125000000335 thiazolyl group Chemical group 0.000 claims description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
239000004480 active ingredient Substances 0.000 claims description 7
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 7
125000001041 indolyl group Chemical group 0.000 claims description 7
239000008194 pharmaceutical composition Substances 0.000 claims description 7
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
125000001544 thienyl group Chemical group 0.000 claims description 7
208000007920 Neurogenic Inflammation Diseases 0.000 claims description 6
208000006673 asthma Diseases 0.000 claims description 6
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 6
125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims description 6
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 6
239000003937 drug carrier Substances 0.000 claims description 6
125000002541 furyl group Chemical group 0.000 claims description 6
125000002883 imidazolyl group Chemical group 0.000 claims description 6
125000000842 isoxazolyl group Chemical group 0.000 claims description 6
229940126601 medicinal product Drugs 0.000 claims description 6
125000002757 morpholinyl group Chemical group 0.000 claims description 6
125000004193 piperazinyl group Chemical group 0.000 claims description 6
125000003386 piperidinyl group Chemical group 0.000 claims description 6
125000003373 pyrazinyl group Chemical group 0.000 claims description 6
125000002098 pyridazinyl group Chemical group 0.000 claims description 6
125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
230000020341 sensory perception of pain Effects 0.000 claims description 6
125000004429 atom Chemical group 0.000 claims description 5
125000003226 pyrazolyl group Chemical group 0.000 claims description 5
229920006395 saturated elastomer Polymers 0.000 claims description 5
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 4
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 4
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 4
125000004414 alkyl thio group Chemical group 0.000 claims description 4
125000004103 aminoalkyl group Chemical group 0.000 claims description 4
125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
238000005984 hydrogenation reaction Methods 0.000 claims description 4
125000001786 isothiazolyl group Chemical group 0.000 claims description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
125000000160 oxazolidinyl group Chemical group 0.000 claims description 4
125000002971 oxazolyl group Chemical group 0.000 claims description 4
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 4
125000001113 thiadiazolyl group Chemical group 0.000 claims description 4
229930195735 unsaturated hydrocarbon Natural products 0.000 claims description 4
230000002485 urinary effect Effects 0.000 claims description 4
206010046543 Urinary incontinence Diseases 0.000 claims description 3
125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 claims description 3
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 3
125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 claims description 2
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims description 2
125000005883 dithianyl group Chemical group 0.000 claims description 2
125000002632 imidazolidinyl group Chemical group 0.000 claims description 2
125000002636 imidazolinyl group Chemical group 0.000 claims description 2
125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 2
125000003072 pyrazolidinyl group Chemical group 0.000 claims description 2
125000002755 pyrazolinyl group Chemical group 0.000 claims description 2
125000001422 pyrrolinyl group Chemical group 0.000 claims description 2
125000004568 thiomorpholinyl group Chemical group 0.000 claims description 2
125000004306 triazinyl group Chemical group 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 3
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims 2
125000004435 hydrogen atom Chemical class [H]* 0.000 claims 2
CUCUKLJLRRAKFN-UHFFFAOYSA-N 7-Hydroxy-(S)-usnate Chemical compound CC12C(=O)C(C(=O)C)C(=O)C=C1OC1=C2C(O)=C(C)C(O)=C1C(C)=O CUCUKLJLRRAKFN-UHFFFAOYSA-N 0.000 claims 1
208000017164 Chronobiology disease Diseases 0.000 claims 1
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims 1
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims 1
238000012876 topography Methods 0.000 claims 1
239000000203 mixture Substances 0.000 abstract description 141
230000003042 antagnostic effect Effects 0.000 abstract description 12
125000000815 N-oxide group Chemical group 0.000 abstract 1
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239000002904 solvent Substances 0.000 description 116
239000000243 solution Substances 0.000 description 73
239000011541 reaction mixture Substances 0.000 description 56
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 53
239000000741 silica gel Substances 0.000 description 45
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238000004440 column chromatography Methods 0.000 description 43
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 42
239000007795 chemical reaction product Substances 0.000 description 40
238000010828 elution Methods 0.000 description 39
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 36
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 35
238000006243 chemical reaction Methods 0.000 description 35
239000012044 organic layer Substances 0.000 description 34
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
239000002585 base Chemical class 0.000 description 30
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229940125782 compound 2 Drugs 0.000 description 29
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RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 description 15
102100024304 Protachykinin-1 Human genes 0.000 description 15
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ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
- 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
- A61P11/06—Antiasthmatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
- 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
- A61P25/22—Anxiolytics
- 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
- A61P25/24—Antidepressants
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- 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
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

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Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Psychiatry (AREA)
Pulmonology (AREA)
Hospice & Palliative Care (AREA)
Pain & Pain Management (AREA)
Otolaryngology (AREA)
Urology & Nephrology (AREA)
Immunology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

UAA200505412A 2002-12-23 2003-12-17 Заміщені похідні 1-піперидин-4-іл-4-піролідин-3-ілпіперазину та їх застосування як антагоністів нейрокінінів UA80584C2 (uk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP0214831		2002-12-23
PCT/EP2003/051041 WO2004056799A2 (en)	2002-12-23	2003-12-17	Substituted 1-piperidin-4-yl-4-pyrrolidin-3-yl-piperazine derivatives and their use as neurokinin antagonists

Publications (1)

Publication Number	Publication Date
UA80584C2 true UA80584C2 (uk)	2007-10-10

Family

ID=32668698

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
UAA200505412A UA80584C2 (uk)	2002-12-23	2003-12-17	Заміщені похідні 1-піперидин-4-іл-4-піролідин-3-ілпіперазину та їх застосування як антагоністів нейрокінінів

Country Status (31)

Country	Link
US (1)	US7795261B2 (da)
EP (1)	EP1581518B1 (da)
JP (1)	JP4746878B2 (da)
KR (1)	KR101049073B1 (da)
CN (1)	CN100586945C (da)
AR (1)	AR042651A1 (da)
AT (1)	ATE500242T1 (da)
AU (1)	AU2003302488B2 (da)
BR (1)	BR0317658A (da)
CA (1)	CA2508657C (da)
CL (1)	CL2003002725A1 (da)
CY (1)	CY1112601T1 (da)
DE (1)	DE60336266D1 (da)
DK (1)	DK1581518T3 (da)
EA (1)	EA009078B1 (da)
ES (1)	ES2361161T3 (da)
HK (1)	HK1087703A1 (da)
HR (1)	HRP20050556B1 (da)
IL (1)	IL169336A (da)
JO (1)	JO2696B1 (da)
MX (1)	MXPA05006887A (da)
MY (1)	MY145135A (da)
NO (1)	NO331174B1 (da)
NZ (1)	NZ541035A (da)
PA (1)	PA8593301A1 (da)
PL (1)	PL376048A1 (da)
PT (1)	PT1581518E (da)
SI (1)	SI1581518T1 (da)
TW (1)	TWI329109B (da)
UA (1)	UA80584C2 (da)
WO (1)	WO2004056799A2 (da)

Families Citing this family (22)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR2847160A1 (fr) *	2002-11-20	2004-05-21	Oreal	Composition capillaire contenant un compose pyrasol-carboxamide, son utilisation pour stimuler la pousse des cheveux et/ou freiner leur chute
ES2431524T3 (es)	2004-04-13	2013-11-26	Incyte Corporation	Derivados de piperazinilpiperidina como antagonistas de los receptores de quimiocinas
WO2005123081A2 (en) *	2004-06-22	2005-12-29	Janssen Pharmaceutica N.V.	(2-benzyl-4-{4-[1-(tetrahydrofuran-3-carbonyl)-pyrrolidin-3-yl]-piperazin-1-yl}-piperidin-1-yl)-(3,5-trifluoromethyl-phenyl))-methanone for the treatment of schizophrenia
WO2006071958A1 (en)	2004-12-29	2006-07-06	Millennium Pharmaceuticals, Inc.	Compounds useful as chemokine receptor antagonists
WO2006071875A1 (en) *	2004-12-29	2006-07-06	Millennium Pharmaceuticals, Inc.	Compounds useful as chemokine receptor antagonists
AU2006221984C1 (en) *	2005-03-08	2012-02-09	Janssen Pharmaceutica N.V.	Diaza-spiro-[4.4]-nonane derivatives as neurokinin (NK1) antagonists
DE102005038947A1 (de) *	2005-05-18	2006-11-30	Grünenthal GmbH	Substituierte Benzo[d]isoxazol-3-yl-amin-Verbindungen und deren Verwendung in Arzneimitteln
CA2669917A1 (en) *	2006-11-17	2008-05-22	Dawn M. George	Aminopyrrolidines as chemokine receptor antagonists
RU2442786C2 (ru) *	2007-03-31	2012-02-20	Интервет Интернэшнл Б.В.	Способы получения зилпатерола и его солей
KR101240147B1 (ko)	2007-03-31	2013-03-08	인터벳 인터내셔널 비.브이.	질파테롤 및 이의 염의 제조 방법
HUE028171T2 (en) *	2007-03-31	2016-12-28	Intervet Int Bv	Methods for preparing zilpaterol and its salts
US7879802B2 (en)	2007-06-04	2011-02-01	Synergy Pharmaceuticals Inc.	Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders
US8969514B2 (en)	2007-06-04	2015-03-03	Synergy Pharmaceuticals, Inc.	Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases
ATE486058T1 (de) *	2007-06-07	2010-11-15	Hoffmann La Roche	Prolinamidderivate als nk3-antagonisten
ES2624828T3 (es)	2008-07-16	2017-07-17	Synergy Pharmaceuticals Inc.	Agonistas de la guanilato ciclasa útiles para el tratamiento de trastornos gastrointestinales, inflamación, cáncer y otros
US8507535B2 (en) *	2010-07-07	2013-08-13	Hoffmann-La Roche Inc.	Methyl-pyrrolidine ether derivatives
SG11201501036RA (en) *	2012-08-23	2015-03-30	Alios Biopharma Inc	Compounds for the treatment of paramoxyvirus viral infections
CA2905438A1 (en)	2013-03-15	2014-09-25	Synergy Pharmaceuticals Inc.	Agonists of guanylate cyclase and their uses
AU2014235209B2 (en)	2013-03-15	2018-06-14	Bausch Health Ireland Limited	Guanylate cyclase receptor agonists combined with other drugs
CN107635557A (zh)	2015-05-18	2018-01-26	尼尔医疗有限公司	用于治疗性激素依赖性疾病的双重nk‑1/nk‑3受体拮抗剂
CN112292132A (zh)	2018-03-14	2021-01-29	KaNDy治疗有限公司	含有双重nk-1/nk-3受体拮抗剂的新颖的药物制剂
US11034669B2 (en)	2018-11-30	2021-06-15	Nuvation Bio Inc.	Pyrrole and pyrazole compounds and methods of use thereof

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
MY110227A (en)	1991-08-12	1998-03-31	Ciba Geigy Ag	1-acylpiperindine compounds.
NZ321575A (en)	1995-10-30	1999-05-28	Janssen Pharmaceutica Nv	1-(1,2-disubstituted piperidinyl)-4- substituted piperazine derivatives
TW382017B (en)	1995-12-27	2000-02-11	Janssen Pharmaceutica Nv	1-(1,2-disubstituted piperidinyl)-4-(fused imidazole)-piperidine derivatives
AU7788500A (en)	1999-10-25	2001-05-08	Janssen Pharmaceutica N.V.	Use of substance p antagonists for influencing the circadian timing system
GB0025354D0 (en)	2000-10-17	2000-11-29	Glaxo Group Ltd	Chemical compounds
US6642226B2 (en) *	2001-02-06	2003-11-04	Hoffman-La Roche Inc.	Substituted phenyl-piperidine methanone compounds
FR2820426B1 (fr) *	2001-02-07	2007-05-11	Condat Sa	Gel d'isolation thermique a reticulation controlee pour les lignes de transport d'hydrocarbures petroliers
MY141736A (en)	2002-10-08	2010-06-15	Elanco Animal Health Ireland	Substituted 1,4-di-piperidin-4-yi-piperazine derivatives and their use as neurokinin antagonists

2003
- 2003-12-15 JO JO2003174A patent/JO2696B1/en active
- 2003-12-17 AT AT03810849T patent/ATE500242T1/de active
- 2003-12-17 CA CA2508657A patent/CA2508657C/en not_active Expired - Fee Related
- 2003-12-17 EP EP03810849A patent/EP1581518B1/en not_active Expired - Lifetime
- 2003-12-17 CN CN200380106356A patent/CN100586945C/zh not_active Expired - Fee Related
- 2003-12-17 KR KR1020057009197A patent/KR101049073B1/ko not_active IP Right Cessation
- 2003-12-17 WO PCT/EP2003/051041 patent/WO2004056799A2/en active Application Filing
- 2003-12-17 ES ES03810849T patent/ES2361161T3/es not_active Expired - Lifetime
- 2003-12-17 MX MXPA05006887A patent/MXPA05006887A/es active IP Right Grant
- 2003-12-17 DK DK03810849.4T patent/DK1581518T3/da active
- 2003-12-17 PL PL03376048A patent/PL376048A1/xx not_active Application Discontinuation
- 2003-12-17 EA EA200501041A patent/EA009078B1/ru not_active IP Right Cessation
- 2003-12-17 PT PT03810849T patent/PT1581518E/pt unknown
- 2003-12-17 UA UAA200505412A patent/UA80584C2/uk unknown
- 2003-12-17 US US10/540,447 patent/US7795261B2/en not_active Expired - Fee Related
- 2003-12-17 SI SI200331992T patent/SI1581518T1/sl unknown
- 2003-12-17 AU AU2003302488A patent/AU2003302488B2/en not_active Ceased
- 2003-12-17 DE DE60336266T patent/DE60336266D1/de not_active Expired - Lifetime
- 2003-12-17 JP JP2004561504A patent/JP4746878B2/ja not_active Expired - Fee Related
- 2003-12-17 BR BR0317658-4A patent/BR0317658A/pt not_active IP Right Cessation
- 2003-12-17 NZ NZ541035A patent/NZ541035A/en not_active IP Right Cessation
- 2003-12-19 PA PA20038593301A patent/PA8593301A1/es unknown
- 2003-12-19 MY MYPI20034909A patent/MY145135A/en unknown
- 2003-12-22 AR ARP030104776A patent/AR042651A1/es unknown
- 2003-12-22 TW TW092136343A patent/TWI329109B/zh not_active IP Right Cessation
- 2003-12-22 CL CL200302725A patent/CL2003002725A1/es unknown
2005
- 2005-06-15 HR HRP20050556AA patent/HRP20050556B1/hr not_active IP Right Cessation
- 2005-06-22 IL IL169336A patent/IL169336A/en not_active IP Right Cessation
- 2005-07-21 NO NO20053569A patent/NO331174B1/no not_active IP Right Cessation
2006
- 2006-07-14 HK HK06107904.4A patent/HK1087703A1/xx not_active IP Right Cessation
2011
- 2011-06-01 CY CY20111100532T patent/CY1112601T1/el unknown

Also Published As

Publication number	Publication date
WO2004056799A3 (en)	2004-08-12
CY1112601T1 (el)	2016-02-10
IL169336A (en)	2013-01-31
CA2508657A1 (en)	2004-07-08
KR101049073B1 (ko)	2011-07-15
MY145135A (en)	2011-12-30
JO2696B1 (en)	2013-03-03
JP2006514027A (ja)	2006-04-27
IL169336A0 (en)	2007-07-04
SI1581518T1 (sl)	2011-06-30
NO20053569D0 (no)	2005-07-21
PA8593301A1 (es)	2004-08-31
WO2004056799A2 (en)	2004-07-08
DE60336266D1 (de)	2011-04-14
PT1581518E (pt)	2011-05-12
HRP20050556B1 (hr)	2014-03-28
EP1581518B1 (en)	2011-03-02
AU2003302488B2 (en)	2009-10-08
HRP20050556A2 (en)	2006-07-31
NZ541035A (en)	2008-05-30
AU2003302488A1 (en)	2004-07-14
KR20050085098A (ko)	2005-08-29
US20060040950A1 (en)	2006-02-23
TWI329109B (en)	2010-08-21
PL376048A1 (en)	2005-12-12
CN100586945C (zh)	2010-02-03
US7795261B2 (en)	2010-09-14
ATE500242T1 (de)	2011-03-15
AR042651A1 (es)	2005-06-29
TW200500359A (en)	2005-01-01
CL2003002725A1 (es)	2005-04-08
DK1581518T3 (da)	2011-06-06
CA2508657C (en)	2013-02-19
ES2361161T3 (es)	2011-06-14
EA200501041A1 (ru)	2005-12-29
EP1581518A2 (en)	2005-10-05
BR0317658A (pt)	2005-12-06
MXPA05006887A (es)	2005-08-16
NO331174B1 (no)	2011-10-24
CN1726207A (zh)	2006-01-25
HK1087703A1 (en)	2006-10-20
JP4746878B2 (ja)	2011-08-10
NO20053569L (no)	2005-09-15
EA009078B1 (ru)	2007-10-26

Publication	Publication Date	Title
UA80584C2 (uk)	2007-10-10	Заміщені похідні 1-піперидин-4-іл-4-піролідин-3-ілпіперазину та їх застосування як антагоністів нейрокінінів
JP5094422B2 (ja)	2012-12-12	置換されたオキサ−ジアザ−スピロ−［５．５］−ウンデカノン誘導体およびニューロキニン拮抗物質としてのそれらの使用
AU2005231984B2 (en)	2011-03-03	Substituted diaza-spiro-[4.5]-decane derivatives and their use as neurokinin antagonists
TWI389901B (zh)	2013-03-21	經取代之二氮雜-螺-〔５．５〕-十一烷衍生物及其等作為神經激肽拮抗劑之用途
EA009217B1 (ru)	2007-12-28	Замещенные производные 1,4-дипиперидин-4-илпиперазина и их применение в качестве нейрокининовых антагонистов
ES2307169T3 (es)	2008-11-16	Derivados 4-alquil y 4-alcanoil piperidina sustituidos y su uso como antagonistas de la neuroquinina.
KR101388453B1 (ko)	2014-04-23	뉴로키닌 (ｎｋ１) 길항제로서의디아자-스피로-[４.４]-노난 유도체
ES2310260T3 (es)	2009-01-01	Derivados sustituidos de 4-(4-piperidin-4-il-piperazin-1-il)-azepan y su uso como antagonistas de la neuroquinina.
AU2003300578B2 (en)	2009-06-04	Substituted 1-piperidin-3-yl-4-piperidin-4-yl-piperazine derivatives and their use as neurokinin antagonists
UA81918C2 (uk)	2008-02-25	Заміщені похідні 1,4-дипіперидин-4-ілпіперазину та їх застосування як нейрокінінових антагоністів
EP1578425A1 (en)	2005-09-28	Substituted 1-piperidin-3-yl-4-piperidin-4-yl-piperazine derivatives and their use as neurokinin antagonists
ZA200505070B (en)	2006-09-27	Substituted 1-piperidin-3-yl-4-piperidin-4-yl-piperazine derivatives and their use as neurokinin antagonists