UA77775C2 - 2,3 diaril-pyparazolidine derivatives inhibiting enzymes degrading neurotensin, pharmaceutical conmposition - Google Patents

2,3 diaril-pyparazolidine derivatives inhibiting enzymes degrading neurotensin, pharmaceutical conmposition Download PDF

Info

Publication number: UA77775C2
Authority: UA; Ukraine
Prior art keywords: alkyl; hydrogen; nitrogen; carbon; halogen
Prior art date: 2002-03-18

Application number

UA20041008453A

Other languages

English (en)

Ukrainian (uk)

Inventor

Rulof V Fenstra

Josephus H M Lange

Maria L Pras-Raves

Cornelis G Kruse

Stuivenberg Herman G Van

Hiskias G Keizer

Original Assignee

Solvay Pharm Bv

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.)

2002-03-18

Filing date

2003-03-17

Publication date

2007-01-15

2003-03-17 Application filed by Solvay Pharm Bv filed Critical Solvay Pharm Bv

2007-01-15 Publication of UA77775C2 publication Critical patent/UA77775C2/uk

Links

102000050267 Neurotensin Human genes 0.000 title claims abstract description 11
101800001814 Neurotensin Proteins 0.000 title claims abstract description 11
PCJGZPGTCUMMOT-ISULXFBGSA-N neurotensin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 PCJGZPGTCUMMOT-ISULXFBGSA-N 0.000 title claims abstract description 8
108090000790 Enzymes Proteins 0.000 title abstract description 6
102000004190 Enzymes Human genes 0.000 title abstract description 6
230000002401 inhibitory effect Effects 0.000 title abstract description 4
230000000593 degrading effect Effects 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 40
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 9
201000010099 disease Diseases 0.000 claims abstract description 4
230000001404 mediated effect Effects 0.000 claims abstract description 3
125000000217 alkyl group Chemical group 0.000 claims description 22
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
229910052739 hydrogen Inorganic materials 0.000 claims description 18
239000001257 hydrogen Substances 0.000 claims description 18
229910052799 carbon Inorganic materials 0.000 claims description 16
229910052757 nitrogen Inorganic materials 0.000 claims description 16
229910052736 halogen Inorganic materials 0.000 claims description 14
150000002367 halogens Chemical class 0.000 claims description 13
125000003545 alkoxy group Chemical group 0.000 claims description 12
238000000034 method Methods 0.000 claims description 10
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
238000002360 preparation method Methods 0.000 claims description 6
125000004432 carbon atom Chemical group C* 0.000 claims description 4
125000004663 dialkyl amino group Chemical group 0.000 claims description 4
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
208000018737 Parkinson disease Diseases 0.000 claims description 2
208000028017 Psychotic disease Diseases 0.000 claims description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
238000004440 column chromatography Methods 0.000 claims description 2
125000004122 cyclic group Chemical group 0.000 claims description 2
125000000753 cycloalkyl group Chemical group 0.000 claims description 2
230000036540 impulse transmission Effects 0.000 claims description 2
229910052760 oxygen Inorganic materials 0.000 claims description 2
239000001301 oxygen Substances 0.000 claims description 2
150000003839 salts Chemical class 0.000 claims description 2
125000004963 sulfonylalkyl group Chemical group 0.000 claims description 2
239000008194 pharmaceutical composition Substances 0.000 claims 6
208000020401 Depressive disease Diseases 0.000 claims 1
239000004480 active ingredient Substances 0.000 claims 1
208000004209 confusion Diseases 0.000 claims 1
230000005540 biological transmission Effects 0.000 abstract 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 44
239000000243 solution Substances 0.000 description 20
239000011541 reaction mixture Substances 0.000 description 18
239000002244 precipitate Substances 0.000 description 17
238000003756 stirring Methods 0.000 description 15
238000006243 chemical reaction Methods 0.000 description 11
239000002904 solvent Substances 0.000 description 11
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
239000002274 desiccant Substances 0.000 description 10
239000003480 eluent Substances 0.000 description 9
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
239000012299 nitrogen atmosphere Substances 0.000 description 8
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
238000010828 elution Methods 0.000 description 6
238000002844 melting Methods 0.000 description 6
230000008018 melting Effects 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
239000003208 petroleum Substances 0.000 description 6
239000000843 powder Substances 0.000 description 6
239000000725 suspension Substances 0.000 description 6
FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 5
-1 2-chloro-1,3-dimethylimidazolinium hexafluorophosphate Chemical compound 0.000 description 5
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 5
AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 5
238000001914 filtration Methods 0.000 description 5
239000000203 mixture Substances 0.000 description 5
239000000047 product Substances 0.000 description 5
239000013049 sediment Substances 0.000 description 5
WXUAQHNMJWJLTG-UHFFFAOYSA-N 2-methylbutanedioic acid Chemical compound OC(=O)C(C)CC(O)=O WXUAQHNMJWJLTG-UHFFFAOYSA-N 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
239000012267 brine Substances 0.000 description 4
208000035475 disorder Diseases 0.000 description 4
239000000155 melt Substances 0.000 description 4
239000000377 silicon dioxide Substances 0.000 description 4
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
239000012141 concentrate Substances 0.000 description 3
239000007790 solid phase Substances 0.000 description 3
229940014800 succinic anhydride Drugs 0.000 description 3
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
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
235000019439 ethyl acetate Nutrition 0.000 description 2
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
VSKMVAJFNWCWPG-UHFFFAOYSA-N n-methyladamantan-2-amine Chemical compound C1C(C2)CC3CC1C(NC)C2C3 VSKMVAJFNWCWPG-UHFFFAOYSA-N 0.000 description 2
150000003218 pyrazolidines Chemical class 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
239000007787 solid Substances 0.000 description 2
239000007858 starting material Substances 0.000 description 2
KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
PENWGQNPFRRVQI-UHFFFAOYSA-N (2-fluorophenyl)hydrazine Chemical compound NNC1=CC=CC=C1F PENWGQNPFRRVQI-UHFFFAOYSA-N 0.000 description 1
KOFLVDBWRHFSAB-UHFFFAOYSA-N 1,2,4,5-tetrahydro-1-(phenylmethyl)-5,9b(1',2')-benzeno-9bh-benz(g)indol-3(3ah)-one Chemical compound C1C(C=2C3=CC=CC=2)C2=CC=CC=C2C23C1C(=O)CN2CC1=CC=CC=C1 KOFLVDBWRHFSAB-UHFFFAOYSA-N 0.000 description 1
YNQXOOPPJWSXMW-UHFFFAOYSA-N 1-ethenyl-2-fluorobenzene Chemical compound FC1=CC=CC=C1C=C YNQXOOPPJWSXMW-UHFFFAOYSA-N 0.000 description 1
VHQIDCCICPFCOG-UHFFFAOYSA-N 2-isocyanatoadamantane Chemical compound C1C(C2)CC3CC1C(N=C=O)C2C3 VHQIDCCICPFCOG-UHFFFAOYSA-N 0.000 description 1
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 1
OAMWNDMMJLINIH-UHFFFAOYSA-N 4-amino-3-methyl-4-oxobutanoic acid Chemical compound NC(=O)C(C)CC(O)=O OAMWNDMMJLINIH-UHFFFAOYSA-N 0.000 description 1
208000019901 Anxiety disease Diseases 0.000 description 1
101000616562 Danio rerio Sonic hedgehog protein A Proteins 0.000 description 1
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
206010062717 Increased upper airway secretion Diseases 0.000 description 1
241001077660 Molo Species 0.000 description 1
108090000812 Neurolysin Proteins 0.000 description 1
102100023072 Neurolysin, mitochondrial Human genes 0.000 description 1
229930040373 Paraformaldehyde Natural products 0.000 description 1
QZWNXXINFABALM-UHFFFAOYSA-N adamantan-2-amine Chemical compound C1C(C2)CC3CC1C(N)C2C3 QZWNXXINFABALM-UHFFFAOYSA-N 0.000 description 1
IYKFYARMMIESOX-UHFFFAOYSA-N adamantanone Chemical compound C1C(C2)CC3CC1C(=O)C2C3 IYKFYARMMIESOX-UHFFFAOYSA-N 0.000 description 1
238000005576 amination reaction Methods 0.000 description 1
230000036506 anxiety Effects 0.000 description 1
230000036772 blood pressure Effects 0.000 description 1
244000309464 bull Species 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
238000001816 cooling Methods 0.000 description 1
239000012043 crude product Substances 0.000 description 1
239000013078 crystal Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
238000001035 drying Methods 0.000 description 1
238000013504 emergency use authorization Methods 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
230000030136 gastric emptying Effects 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
239000005457 ice water Substances 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
RIVIDPPYRINTTH-UHFFFAOYSA-N n-ethylpropan-2-amine Chemical compound CCNC(C)C RIVIDPPYRINTTH-UHFFFAOYSA-N 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
108010032563 oligopeptidase Proteins 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
229920002866 paraformaldehyde Polymers 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
208000026435 phlegm Diseases 0.000 description 1
BULVZWIRKLYCBC-UHFFFAOYSA-N phorate Chemical compound CCOP(=S)(OCC)SCSCC BULVZWIRKLYCBC-UHFFFAOYSA-N 0.000 description 1
208000020016 psychiatric disease Diseases 0.000 description 1
150000003235 pyrrolidines Chemical class 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
238000010992 reflux Methods 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
238000000926 separation method Methods 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000001384 succinic acid Substances 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
238000007738 vacuum evaporation Methods 0.000 description 1

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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/04—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Pain & Pain Management (AREA)
Psychiatry (AREA)
Psychology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Plural Heterocyclic Compounds (AREA)

UA20041008453A 2002-03-18 2003-03-17 2,3 diaril-pyparazolidine derivatives inhibiting enzymes degrading neurotensin, pharmaceutical conmposition UA77775C2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP02076482		2002-03-18
PCT/EP2003/050064 WO2003078400A1 (en)	2002-03-18	2003-03-17	Neurotensin active 2,3-diaryl-pyrazolidine derivatives

Publications (1)

Publication Number	Publication Date
UA77775C2 true UA77775C2 (en)	2007-01-15

Family

ID=27838122

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
UA20041008453A UA77775C2 (en)	2002-03-18	2003-03-17	2,3 diaril-pyparazolidine derivatives inhibiting enzymes degrading neurotensin, pharmaceutical conmposition

Country Status (24)

Country	Link
US (1)	US7186741B2 (da)
EP (1)	EP1487802B1 (da)
JP (1)	JP4484525B2 (da)
KR (1)	KR20040106290A (da)
CN (1)	CN100509788C (da)
AR (1)	AR038967A1 (da)
AT (1)	ATE493390T1 (da)
AU (1)	AU2003219165B2 (da)
BR (1)	BR0306149A (da)
CA (1)	CA2462694C (da)
DE (1)	DE60335525D1 (da)
DK (1)	DK1487802T3 (da)
ES (1)	ES2358894T3 (da)
HR (1)	HRP20040275A2 (da)
IL (1)	IL160944A0 (da)
MX (1)	MXPA04004743A (da)
NO (1)	NO20044405L (da)
PL (1)	PL371440A1 (da)
PT (1)	PT1487802E (da)
RU (1)	RU2304578C2 (da)
SI (1)	SI1487802T1 (da)
UA (1)	UA77775C2 (da)
WO (1)	WO2003078400A1 (da)
ZA (1)	ZA200404741B (da)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP1801098A1 (en)	2005-12-16	2007-06-27	Merck Sante	2-Adamantylurea derivatives as selective 11B-HSD1 inhibitors
CN102241678B (zh)	2011-04-26	2014-10-29	辽宁利锋科技开发有限公司	含有脂环结构化合物的抗肿瘤作用与应用
WO2015188073A1 (en)	2014-06-06	2015-12-10	Research Triangle Institute	Apelin receptor (apj) agonists and uses thereof
AU2016366310C1 (en)	2015-12-09	2021-09-09	Research Triangle Institute	Improved apelin receptor (APJ) agonists and uses thereof
KR20220054391A (ko)	2019-08-29	2022-05-02	리서치 트라이앵글 인스티튜트	아펠린 수용체 작용제에 대한 방법 및 용도
CN117180430B (zh) *	2023-08-23	2025-03-14	四川大学华西医院	Nln神经溶素在制备作为治疗肺癌药物的用途

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE3712365A1 (de)	1987-04-11	1988-10-27	Hoechst Ag	Neue 2-acylpyrrolidin-derivate, verfahren zu ihrer herstellung, sie enthaltende mittel sowie deren verwendung
PH27357A (en) *	1989-09-22	1993-06-21	Fujisawa Pharmaceutical Co	Pyrazole derivatives and pharmaceutical compositions comprising the same
FR2665898B1 (fr) *	1990-08-20	1994-03-11	Sanofi	Derives d'amido-3 pyrazole, procede pour leur preparation et compositions pharmaceutiques les contenant.
FR2711140B1 (fr) *	1993-10-12	1996-01-05	Sanofi Sa	1-Naphtylpyrazole-3-carboxamides substitués actifs sur la neurotensine, leur préparation, les compositions pharmaceutiques en contenant.
FR2722193B1 (fr) *	1994-07-08	1996-10-04	Sanofi Sa	Derives n-oxydes de 1-(7-chloro-4-quinoleinyl)pyrazole-3-carboxamides substitues, procede pour leur preparation et les compositions pharmaceitiques les contenant

2003
- 2003-03-13 AR ARP030100880A patent/AR038967A1/es unknown
- 2003-03-17 PT PT03714961T patent/PT1487802E/pt unknown
- 2003-03-17 EP EP03714961A patent/EP1487802B1/en not_active Expired - Lifetime
- 2003-03-17 MX MXPA04004743A patent/MXPA04004743A/es active IP Right Grant
- 2003-03-17 PL PL03371440A patent/PL371440A1/xx not_active Application Discontinuation
- 2003-03-17 DE DE60335525T patent/DE60335525D1/de not_active Expired - Lifetime
- 2003-03-17 WO PCT/EP2003/050064 patent/WO2003078400A1/en not_active Ceased
- 2003-03-17 KR KR10-2004-7014581A patent/KR20040106290A/ko not_active Ceased
- 2003-03-17 IL IL16094403A patent/IL160944A0/xx unknown
- 2003-03-17 AT AT03714961T patent/ATE493390T1/de active
- 2003-03-17 AU AU2003219165A patent/AU2003219165B2/en not_active Ceased
- 2003-03-17 CN CNB038015668A patent/CN100509788C/zh not_active Expired - Fee Related
- 2003-03-17 US US10/490,549 patent/US7186741B2/en not_active Expired - Fee Related
- 2003-03-17 HR HR20040275A patent/HRP20040275A2/hr not_active Application Discontinuation
- 2003-03-17 SI SI200331966T patent/SI1487802T1/sl unknown
- 2003-03-17 ES ES03714961T patent/ES2358894T3/es not_active Expired - Lifetime
- 2003-03-17 BR BR0306149-3A patent/BR0306149A/pt not_active IP Right Cessation
- 2003-03-17 RU RU2004114262/04A patent/RU2304578C2/ru not_active IP Right Cessation
- 2003-03-17 JP JP2003576406A patent/JP4484525B2/ja not_active Expired - Fee Related
- 2003-03-17 CA CA2462694A patent/CA2462694C/en not_active Expired - Fee Related
- 2003-03-17 UA UA20041008453A patent/UA77775C2/uk unknown
- 2003-03-17 DK DK03714961.4T patent/DK1487802T3/da active
2004
- 2004-06-15 ZA ZA200404741A patent/ZA200404741B/en unknown
- 2004-10-15 NO NO20044405A patent/NO20044405L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
ES2358894T3 (es)	2011-05-16
CA2462694A1 (en)	2003-09-25
RU2004114262A (ru)	2005-09-20
AR038967A1 (es)	2005-02-02
AU2003219165B2 (en)	2008-03-13
IL160944A0 (en)	2004-08-31
PT1487802E (pt)	2011-03-11
DE60335525D1 (de)	2011-02-10
CN100509788C (zh)	2009-07-08
NO20044405L (no)	2004-10-15
CN1592742A (zh)	2005-03-09
RU2304578C2 (ru)	2007-08-20
EP1487802A1 (en)	2004-12-22
AU2003219165A1 (en)	2003-09-29
US20040242493A1 (en)	2004-12-02
KR20040106290A (ko)	2004-12-17
WO2003078400A1 (en)	2003-09-25
US7186741B2 (en)	2007-03-06
JP2005527528A (ja)	2005-09-15
EP1487802B1 (en)	2010-12-29
SI1487802T1 (sl)	2011-04-29
HRP20040275A2 (en)	2004-08-31
PL371440A1 (en)	2005-06-13
ZA200404741B (en)	2005-08-29
CA2462694C (en)	2010-08-10
DK1487802T3 (da)	2011-04-04
HK1070646A1 (zh)	2005-06-24
ATE493390T1 (de)	2011-01-15
BR0306149A (pt)	2004-10-19
MXPA04004743A (es)	2004-08-02
JP4484525B2 (ja)	2010-06-16

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