NO324173B1 - 4,5-dihydro-1H-pyrazolderivater med CB1-antagonistaktivitet, fremgangsmate til fremstilling derav, anvendelse derav til fremstilling av et medikament, en farmasoytisk sammensetning og mellomprodukter - Google Patents

4,5-dihydro-1H-pyrazolderivater med CB1-antagonistaktivitet, fremgangsmate til fremstilling derav, anvendelse derav til fremstilling av et medikament, en farmasoytisk sammensetning og mellomprodukter Download PDF

Info

Publication number: NO324173B1
Authority: NO; Norway
Prior art keywords: phenyl; chlorophenyl; pyrazole; formula; dihydro
Prior art date: 2000-03-23

Application number

NO20024531A

Other languages

English (en)

Norwegian (no)

Other versions

NO20024531L (no

NO20024531D0 (no

Inventor

Cornelis Gerrit Kruse

Jacobus Tipker

Martinus T M Tulp

Josephus H M Lange

Bernardus J Van Vliet

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.)

2000-03-23

Filing date

2002-09-20

Publication date

2007-09-03

2002-09-20 Application filed by Solvay Pharm Bv filed Critical Solvay Pharm Bv

2002-09-20 Publication of NO20024531D0 publication Critical patent/NO20024531D0/no

2002-11-19 Publication of NO20024531L publication Critical patent/NO20024531L/no

2007-09-03 Publication of NO324173B1 publication Critical patent/NO324173B1/no

Links

238000002360 preparation method Methods 0.000 title claims description 11
239000003814 drug Substances 0.000 title claims description 7
238000000034 method Methods 0.000 title claims description 7
229940079593 drug Drugs 0.000 title claims description 4
239000008194 pharmaceutical composition Substances 0.000 title claims description 4
MCGBIXXDQFWVDW-UHFFFAOYSA-N 4,5-dihydro-1h-pyrazole Chemical class C1CC=NN1 MCGBIXXDQFWVDW-UHFFFAOYSA-N 0.000 title abstract description 5
230000000694 effects Effects 0.000 title description 3
229940124802 CB1 antagonist Drugs 0.000 title 1
239000012450 pharmaceutical intermediate Substances 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 160
-1 propionyloxy Chemical group 0.000 claims abstract description 23
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 16
239000001257 hydrogen Substances 0.000 claims abstract description 16
125000000217 alkyl group Chemical group 0.000 claims abstract description 15
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 12
125000004076 pyridyl group Chemical group 0.000 claims abstract description 11
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims abstract description 10
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 9
125000001624 naphthyl group Chemical group 0.000 claims abstract description 8
125000001424 substituent group Chemical group 0.000 claims abstract description 8
125000001544 thienyl group Chemical group 0.000 claims abstract description 7
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 6
125000003545 alkoxy group Chemical group 0.000 claims abstract description 5
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 5
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 4
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims abstract description 3
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UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
150000001412 amines Chemical class 0.000 claims description 9
150000003839 salts Chemical class 0.000 claims description 9
239000003795 chemical substances by application Substances 0.000 claims description 8
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150000002367 halogens Chemical class 0.000 claims description 8
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 8
125000006239 protecting group Chemical group 0.000 claims description 8
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 6
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125000005843 halogen group Chemical group 0.000 claims description 6
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150000002431 hydrogen Chemical class 0.000 claims description 4
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125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 claims description 3
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 3
PMFKSNJVULPDBR-UHFFFAOYSA-N 5-(4-chlorophenyl)-n'-(4-fluorophenyl)sulfonyl-4-phenyl-3,4-dihydropyrazole-2-carboximidamide Chemical compound C1=CC(F)=CC=C1S(=O)(=O)NC(=N)N1N=C(C=2C=CC(Cl)=CC=2)C(C=2C=CC=CC=2)C1 PMFKSNJVULPDBR-UHFFFAOYSA-N 0.000 claims description 3
AXJQVVLKUYCICH-UHFFFAOYSA-N 5-(4-chlorophenyl)-n-(4-chlorophenyl)sulfonyl-n'-methyl-4-phenyl-3,4-dihydropyrazole-2-carboximidamide Chemical compound C1C(C=2C=CC=CC=2)C(C=2C=CC(Cl)=CC=2)=NN1C(=NC)NS(=O)(=O)C1=CC=C(Cl)C=C1 AXJQVVLKUYCICH-UHFFFAOYSA-N 0.000 claims description 3
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208000016620 Tourette disease Diseases 0.000 claims description 3
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 3
230000036506 anxiety Effects 0.000 claims description 3
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 3
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230000006735 deficit Effects 0.000 claims description 3
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 3
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206010015037 epilepsy Diseases 0.000 claims description 3
230000002140 halogenating effect Effects 0.000 claims description 3
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims description 3
NONOKGVFTBWRLD-UHFFFAOYSA-N isocyanatosulfanylimino(oxo)methane Chemical compound O=C=NSN=C=O NONOKGVFTBWRLD-UHFFFAOYSA-N 0.000 claims description 3
235000020824 obesity Nutrition 0.000 claims description 3
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 3
UCQFSGCWHRTMGG-UHFFFAOYSA-N pyrazole-1-carboximidamide Chemical compound NC(=N)N1C=CC=N1 UCQFSGCWHRTMGG-UHFFFAOYSA-N 0.000 claims description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
NRGOZJYSRXOCFH-UHFFFAOYSA-N 4,5-bis(4-methoxyphenyl)-n'-(4-methoxyphenyl)sulfonyl-3,4-dihydropyrazole-2-carboximidamide Chemical compound C1=CC(OC)=CC=C1C1C(C=2C=CC(OC)=CC=2)=NN(C(=N)NS(=O)(=O)C=2C=CC(OC)=CC=2)C1 NRGOZJYSRXOCFH-UHFFFAOYSA-N 0.000 claims description 2
RBDSMVUZBCAAEN-UHFFFAOYSA-N 5-(4-chlorophenyl)-4-phenyl-n'-(2,4,6-trimethylphenyl)sulfonyl-3,4-dihydropyrazole-2-carboximidamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC(=N)N1N=C(C=2C=CC(Cl)=CC=2)C(C=2C=CC=CC=2)C1 RBDSMVUZBCAAEN-UHFFFAOYSA-N 0.000 claims description 2
VHRQDVXOLLGRSP-UHFFFAOYSA-N 5-(4-chlorophenyl)-n'-(4-chlorophenyl)sulfonyl-4-phenyl-n-pyridin-2-yl-3,4-dihydropyrazole-2-carboximidamide Chemical compound C1=CC(Cl)=CC=C1C1=NN(C(\NC=2N=CC=CC=2)=N\S(=O)(=O)C=2C=CC(Cl)=CC=2)CC1C1=CC=CC=C1 VHRQDVXOLLGRSP-UHFFFAOYSA-N 0.000 claims description 2
OVBPZWWNLXSVAC-UHFFFAOYSA-N 5-(4-chlorophenyl)-n'-(4-chlorophenyl)sulfonyl-n,4-diphenyl-3,4-dihydropyrazole-2-carboximidamide Chemical compound C1=CC(Cl)=CC=C1C1=NN(C(\NC=2C=CC=CC=2)=N\S(=O)(=O)C=2C=CC(Cl)=CC=2)CC1C1=CC=CC=C1 OVBPZWWNLXSVAC-UHFFFAOYSA-N 0.000 claims description 2
ATGPYUSOVVWMQP-UHFFFAOYSA-N 5-(4-chlorophenyl)-n'-(4-fluorophenyl)sulfonyl-4-hydroxy-4-phenyl-3h-pyrazole-2-carboximidamide Chemical compound C=1C=CC=CC=1C1(O)CN(C(=N)NS(=O)(=O)C=2C=CC(F)=CC=2)N=C1C1=CC=C(Cl)C=C1 ATGPYUSOVVWMQP-UHFFFAOYSA-N 0.000 claims description 2
XXYLQSSZLZNJAF-UHFFFAOYSA-N 5-(4-chlorophenyl)-n-(4-fluorophenyl)sulfonyl-4-phenyl-n'-propyl-3,4-dihydropyrazole-2-carboximidamide Chemical compound C1C(C=2C=CC=CC=2)C(C=2C=CC(Cl)=CC=2)=NN1C(=NCCC)NS(=O)(=O)C1=CC=C(F)C=C1 XXYLQSSZLZNJAF-UHFFFAOYSA-N 0.000 claims description 2
208000024172 Cardiovascular disease Diseases 0.000 claims description 2
208000018522 Gastrointestinal disease Diseases 0.000 claims description 2
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125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
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208000028867 ischemia Diseases 0.000 claims description 2
BQPIGGFYSBELGY-UHFFFAOYSA-N mercury(2+) Chemical class [Hg+2] BQPIGGFYSBELGY-UHFFFAOYSA-N 0.000 claims description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
YNTNKIJUFXILJN-UHFFFAOYSA-N n'-(4-fluorophenyl)sulfonyl-4,5-bis(4-methoxyphenyl)-3,4-dihydropyrazole-2-carboximidamide Chemical compound C1=CC(OC)=CC=C1C1C(C=2C=CC(OC)=CC=2)=NN(C(=N)NS(=O)(=O)C=2C=CC(F)=CC=2)C1 YNTNKIJUFXILJN-UHFFFAOYSA-N 0.000 claims description 2
LOWNRGJMVVHOEY-UHFFFAOYSA-N n-(4-chlorophenyl)sulfonyl-4-phenyl-n'-propan-2-yl-5-pyridin-4-yl-3,4-dihydropyrazole-2-carboximidamide Chemical compound C1C(C=2C=CC=CC=2)C(C=2C=CN=CC=2)=NN1C(=NC(C)C)NS(=O)(=O)C1=CC=C(Cl)C=C1 LOWNRGJMVVHOEY-UHFFFAOYSA-N 0.000 claims description 2
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125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 claims description 2
125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 claims description 2
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 2
125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 1
RKVDQNXSXIWCQP-UHFFFAOYSA-N 5-(4-chlorophenyl)-n'-(4-chlorophenyl)sulfonyl-n-(dimethylamino)-4-phenyl-3,4-dihydropyrazole-2-carboximidamide Chemical compound C1C(C=2C=CC=CC=2)C(C=2C=CC(Cl)=CC=2)=NN1C(/NN(C)C)=N\S(=O)(=O)C1=CC=C(Cl)C=C1 RKVDQNXSXIWCQP-UHFFFAOYSA-N 0.000 claims 1
CXNXHKUCYNGGIR-UHFFFAOYSA-N 5-(4-chlorophenyl)-n-(4-chlorophenyl)sulfonyl-n'-methyl-4-pyridin-4-yl-3,4-dihydropyrazole-2-carboximidamide Chemical compound C1C(C=2C=CN=CC=2)C(C=2C=CC(Cl)=CC=2)=NN1C(=NC)NS(=O)(=O)C1=CC=C(Cl)C=C1 CXNXHKUCYNGGIR-UHFFFAOYSA-N 0.000 claims 1
MXVJHHZCQUGIBP-UHFFFAOYSA-N 5-(4-chlorophenyl)-n-(4-chlorophenyl)sulfonyl-n-ethyl-4-hydroxy-4-phenyl-3h-pyrazole-2-carboximidamide Chemical compound C=1C=C(Cl)C=CC=1S(=O)(=O)N(CC)C(=N)N(N=1)CC(O)(C=2C=CC=CC=2)C=1C1=CC=C(Cl)C=C1 MXVJHHZCQUGIBP-UHFFFAOYSA-N 0.000 claims 1
RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims 1
PYXYWJZSZZCOFU-UHFFFAOYSA-N n-(4-chlorophenyl)sulfonyl-5-(5-chlorothiophen-2-yl)-n'-methyl-4-phenyl-3,4-dihydropyrazole-2-carboximidamide Chemical compound C1C(C=2C=CC=CC=2)C(C=2SC(Cl)=CC=2)=NN1C(=NC)NS(=O)(=O)C1=CC=C(Cl)C=C1 PYXYWJZSZZCOFU-UHFFFAOYSA-N 0.000 claims 1
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QNYKEYVDTHEXKV-UHFFFAOYSA-N n-[amino-[5-(4-chlorophenyl)-4-phenyl-3,4-dihydropyrazol-2-yl]methylidene]pyridine-2-carboxamide Chemical compound C1=CC(Cl)=CC=C1C1=NN(C(=N)NC(=O)C=2N=CC=CC=2)CC1C1=CC=CC=C1 QNYKEYVDTHEXKV-UHFFFAOYSA-N 0.000 claims 1
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SKLKZKAMWPQZLM-UHFFFAOYSA-N 3-(4-chlorophenyl)-4-phenyl-4,5-dihydro-1h-pyrazole Chemical compound C1=CC(Cl)=CC=C1C1=NNCC1C1=CC=CC=C1 SKLKZKAMWPQZLM-UHFFFAOYSA-N 0.000 description 7
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Classifications

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- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/06—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- 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
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- A61P25/04—Centrally acting analgesics, e.g. opioids
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
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- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- 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
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- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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NO20024531A 2000-03-23 2002-09-20 4,5-dihydro-1H-pyrazolderivater med CB1-antagonistaktivitet, fremgangsmate til fremstilling derav, anvendelse derav til fremstilling av et medikament, en farmasoytisk sammensetning og mellomprodukter NO324173B1 (no)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
NL1014728		2000-03-23
EP00201032		2000-03-23
PCT/EP2001/003247 WO2001070700A1 (fr)	2000-03-23	2001-03-22	Derives de 4,5-dihydro-1h-pyrazole ayant une activite antagoniste de cb¿1?

Publications (3)

Publication Number	Publication Date
NO20024531D0 NO20024531D0 (no)	2002-09-20
NO20024531L NO20024531L (no)	2002-11-19
NO324173B1 true NO324173B1 (no)	2007-09-03

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NO20024531A NO324173B1 (no)	2000-03-23	2002-09-20	4,5-dihydro-1H-pyrazolderivater med CB1-antagonistaktivitet, fremgangsmate til fremstilling derav, anvendelse derav til fremstilling av et medikament, en farmasoytisk sammensetning og mellomprodukter

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US (1)	US6476060B2 (fr)
EP (1)	EP1268435B1 (fr)
JP (1)	JP2004500401A (fr)
KR (1)	KR100800277B1 (fr)
CN (1)	CN1205188C (fr)
AT (1)	ATE346047T1 (fr)
AU (2)	AU2001242501B2 (fr)
BR (1)	BR0109457A (fr)
CA (1)	CA2401832C (fr)
CY (1)	CY1105967T1 (fr)
DE (1)	DE60124685T2 (fr)
DK (1)	DK1268435T3 (fr)
DZ (1)	DZ3335A1 (fr)
ES (1)	ES2272449T3 (fr)
HK (1)	HK1052349B (fr)
HU (1)	HUP0204519A3 (fr)
IL (2)	IL151452A0 (fr)
MX (1)	MXPA02009258A (fr)
NO (1)	NO324173B1 (fr)
PL (1)	PL208098B1 (fr)
PT (1)	PT1268435E (fr)
RU (1)	RU2245878C2 (fr)
SI (1)	SI1268435T1 (fr)
SK (1)	SK287074B6 (fr)
UA (1)	UA74367C2 (fr)
WO (1)	WO2001070700A1 (fr)

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2001
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- 2001-03-22 AT AT01915398T patent/ATE346047T1/de active
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- 2001-03-22 DZ DZ013335A patent/DZ3335A1/fr active
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Also Published As

Publication number	Publication date
CN1419546A (zh)	2003-05-21
DE60124685D1 (de)	2007-01-04
HUP0204519A3 (en)	2003-07-28
DE60124685T2 (de)	2007-03-29
BR0109457A (pt)	2003-06-03
AU4250101A (en)	2001-10-03
KR20020084239A (ko)	2002-11-04
DK1268435T3 (da)	2007-03-12
JP2004500401A (ja)	2004-01-08
NO20024531L (no)	2002-11-19
ES2272449T3 (es)	2007-05-01
RU2245878C2 (ru)	2005-02-10
UA74367C2 (uk)	2005-12-15
WO2001070700A1 (fr)	2001-09-27
RU2002128352A (ru)	2004-02-27
KR100800277B1 (ko)	2008-02-05
US20010053788A1 (en)	2001-12-20
IL151452A (en)	2006-10-05
HK1052349A1 (en)	2003-09-11
CA2401832C (fr)	2010-02-02
PL208098B1 (pl)	2011-03-31
AU2001242501B2 (en)	2004-12-09
NO20024531D0 (no)	2002-09-20
CN1205188C (zh)	2005-06-08
PT1268435E (pt)	2007-02-28
CA2401832A1 (fr)	2001-09-27
SK13522002A3 (sk)	2003-03-04
CY1105967T1 (el)	2011-04-06
EP1268435B1 (fr)	2006-11-22
IL151452A0 (en)	2003-04-10
DZ3335A1 (fr)	2001-09-27
SK287074B6 (sk)	2009-11-05
HK1052349B (zh)	2005-09-23
US6476060B2 (en)	2002-11-05
PL358101A1 (en)	2004-08-09
SI1268435T1 (sl)	2007-02-28
HUP0204519A2 (en)	2003-05-28
MXPA02009258A (es)	2005-04-19
EP1268435A1 (fr)	2003-01-02
ATE346047T1 (de)	2006-12-15

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Publication	Publication Date	Title
CA2401832C (fr)	2010-02-02	Derives de 4,5-dihydro-1h-pyrazole ayant une activite antagoniste de cb1
AU2001242501A1 (en)	2001-12-13	4,5-dihydro-1H-pyrazole derivatives having CB1-antagonistic activity
EP1373216B1 (fr)	2004-12-15	Derives de 4,5-dihydro-1h-pyrazole ayant une activite d'antagoniste de cb 1
CA2442245C (fr)	2010-03-30	Derives 4,5-dihydro-1h-pyrazole presentant une puissante activite antagoniste du recepteur cb1
AU2002333852B2 (en)	2006-07-13	Novel 4,5-dihydro-1H-pyrazole derivativeshaving CB1-antagonistic activity
AU2002256690A1 (en)	2003-03-27	4,5-dihydro-1H-pyrazole derivatives having CB1-antagonistic activity
ZA200207303B (en)	2003-12-11	4,5-dihydro-1H-pyrazole derivatives having CB1-antagonistic activity.
HK1061852B (en)	2008-07-18	4,5-dihydro-ih-pyrazole derivatives having cb1-antagonistic activity