NO330862B1 - Tizolidinon-vinylkondenserte benzenderivater, fremgangsmate for fremstilling derav og anvendelse derav for fremstilling av medikamenter og farmasoytisk sammensetning innholdende samme - Google Patents

Tizolidinon-vinylkondenserte benzenderivater, fremgangsmate for fremstilling derav og anvendelse derav for fremstilling av medikamenter og farmasoytisk sammensetning innholdende samme Download PDF

Info

Publication number: NO330862B1
Authority: NO; Norway
Prior art keywords: dione; thiazolidin; thiazolidine; ylmethylene; methylene
Prior art date: 2002-07-10

Application number

NO20050654A

Other languages

English (en)

Norwegian (no)

Other versions

NO20050654L (no

Inventor

Dennis Church

Pascale Gaillard

Thomas Rueckle

Xuliang Jiang

Tania Valloton

Original Assignee

Serono Lab

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.)

2002-07-10

Filing date

2005-02-08

Publication date

2011-08-01

2002-11-07 Priority claimed from US10/289,998 external-priority patent/US20040092561A1/en

2005-02-08 Application filed by Serono Lab filed Critical Serono Lab

2005-03-15 Publication of NO20050654L publication Critical patent/NO20050654L/no

2011-08-01 Publication of NO330862B1 publication Critical patent/NO330862B1/no

Links

125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 title claims abstract description 36
229920002554 vinyl polymer Polymers 0.000 title claims abstract description 7
238000000034 method Methods 0.000 title claims description 73
238000002360 preparation method Methods 0.000 title claims description 47
239000003814 drug Substances 0.000 title claims description 15
239000008194 pharmaceutical composition Substances 0.000 title claims description 12
229940079593 drug Drugs 0.000 title claims description 8
238000011282 treatment Methods 0.000 claims abstract description 23
238000011321 prophylaxis Methods 0.000 claims abstract description 15
208000010110 spontaneous platelet aggregation Diseases 0.000 claims abstract description 14
208000036142 Viral infection Diseases 0.000 claims abstract description 13
230000001580 bacterial effect Effects 0.000 claims abstract description 13
230000009385 viral infection Effects 0.000 claims abstract description 13
230000004770 neurodegeneration Effects 0.000 claims abstract description 12
208000023275 Autoimmune disease Diseases 0.000 claims abstract description 11
208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 11
208000037979 autoimmune inflammatory disease Diseases 0.000 claims abstract description 11
208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 11
208000035143 Bacterial infection Diseases 0.000 claims abstract description 9
208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 9
208000017169 kidney disease Diseases 0.000 claims abstract description 9
231100000516 lung damage Toxicity 0.000 claims abstract description 9
150000001875 compounds Chemical class 0.000 claims description 153
-1 dihydrobenzodioxin Chemical group 0.000 claims description 124
ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 claims description 67
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 40
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 40
102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 claims description 35
108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 claims description 35
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 26
150000003839 salts Chemical class 0.000 claims description 26
230000000694 effects Effects 0.000 claims description 17
229910052736 halogen Inorganic materials 0.000 claims description 16
150000002367 halogens Chemical group 0.000 claims description 16
229910052739 hydrogen Inorganic materials 0.000 claims description 16
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
239000001257 hydrogen Substances 0.000 claims description 13
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 13
230000004913 activation Effects 0.000 claims description 12
201000010099 disease Diseases 0.000 claims description 12
210000000056 organ Anatomy 0.000 claims description 12
125000004546 quinazolin-4-yl group Chemical group N1=CN=C(C2=CC=CC=C12)* 0.000 claims description 12
206010028980 Neoplasm Diseases 0.000 claims description 11
201000011510 cancer Diseases 0.000 claims description 11
230000005764 inhibitory process Effects 0.000 claims description 10
229910052760 oxygen Inorganic materials 0.000 claims description 10
125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 9
210000000265 leukocyte Anatomy 0.000 claims description 9
IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical group C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims description 8
201000004681 Psoriasis Diseases 0.000 claims description 8
239000003085 diluting agent Substances 0.000 claims description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
150000002431 hydrogen Chemical class 0.000 claims description 8
230000000302 ischemic effect Effects 0.000 claims description 8
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 claims description 7
238000004519 manufacturing process Methods 0.000 claims description 7
201000006417 multiple sclerosis Diseases 0.000 claims description 7
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 6
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 6
210000004072 lung Anatomy 0.000 claims description 6
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125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
210000001519 tissue Anatomy 0.000 claims description 5
HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical group C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 claims description 4
VRUPOBLKXUKQDP-UHFFFAOYSA-N 5-[(2-fluoro-1-benzofuran-6-yl)methylidene]-1,3-thiazolidine-2,4-dione Chemical compound C1=C2OC(F)=CC2=CC=C1C=C1SC(=O)NC1=O VRUPOBLKXUKQDP-UHFFFAOYSA-N 0.000 claims description 4
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UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
208000022559 Inflammatory bowel disease Diseases 0.000 claims description 4
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SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical group N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 4
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QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 4
125000004532 benzofuran-3-yl group Chemical group O1C=C(C2=C1C=CC=C2)* 0.000 claims description 4
IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical group C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 4
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
230000036772 blood pressure Effects 0.000 claims description 4
210000004556 brain Anatomy 0.000 claims description 4
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125000002757 morpholinyl group Chemical group 0.000 claims description 4
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XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims description 4
230000007115 recruitment Effects 0.000 claims description 4
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125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 4
229910052727 yttrium Inorganic materials 0.000 claims description 4
125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 3
UOEYYZINJAEXJM-UHFFFAOYSA-N 3-[5-[(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]-1-benzofuran-3-yl]-n-ethyl-n-(2-hydroxyethyl)prop-2-enamide Chemical compound C1=C2C(C=CC(=O)N(CCO)CC)=COC2=CC=C1C=C1SC(=O)NC1=O UOEYYZINJAEXJM-UHFFFAOYSA-N 0.000 claims description 3
KTZAPRYDZSOKAY-UHFFFAOYSA-N 5-[(4-methoxyquinazolin-6-yl)methylidene]-1,3-thiazolidine-2,4-dione Chemical compound C1=C2C(OC)=NC=NC2=CC=C1C=C1SC(=O)NC1=O KTZAPRYDZSOKAY-UHFFFAOYSA-N 0.000 claims description 3
VKOBZTOMBQFTCE-UHFFFAOYSA-N 5-[(9,10-dioxoanthracen-2-yl)methylidene]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1=CC1=CC=C(C(=O)C=2C(=CC=CC=2)C2=O)C2=C1 VKOBZTOMBQFTCE-UHFFFAOYSA-N 0.000 claims description 3
LDZCZMJFFCQVKA-UHFFFAOYSA-N 5-[[3-[2-[4-(trifluoromethyl)phenyl]ethyl]benzimidazol-5-yl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound C1=CC(C(F)(F)F)=CC=C1CCN1C2=CC(C=C3C(NC(=O)S3)=O)=CC=C2N=C1 LDZCZMJFFCQVKA-UHFFFAOYSA-N 0.000 claims description 3
DAYRVYVBQJJEPT-UHFFFAOYSA-N 5-[[3-[3-(azepan-1-yl)-3-oxoprop-1-enyl]-1-benzofuran-5-yl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound C1CCCCCN1C(=O)C=CC(C1=C2)=COC1=CC=C2C=C1SC(=O)NC1=O DAYRVYVBQJJEPT-UHFFFAOYSA-N 0.000 claims description 3
NZNMSOFKMUBTKW-UHFFFAOYSA-N Cyclohexanecarboxylic acid Natural products OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 claims description 3
208000007536 Thrombosis Diseases 0.000 claims description 3
125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims description 3
VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
125000002541 furyl group Chemical group 0.000 claims description 3
125000001041 indolyl group Chemical group 0.000 claims description 3
230000009401 metastasis Effects 0.000 claims description 3
JJCPMWJNUVZDPD-UHFFFAOYSA-N n-cyclohexyl-3-[5-[(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]-1-benzofuran-3-yl]-n-methylprop-2-enamide Chemical compound C=1OC2=CC=C(C=C3C(NC(=O)S3)=O)C=C2C=1C=CC(=O)N(C)C1CCCCC1 JJCPMWJNUVZDPD-UHFFFAOYSA-N 0.000 claims description 3
XJLSEXAGTJCILF-UHFFFAOYSA-N nipecotic acid Chemical compound OC(=O)C1CCCNC1 XJLSEXAGTJCILF-UHFFFAOYSA-N 0.000 claims description 3
235000019260 propionic acid Nutrition 0.000 claims description 3
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 3
FNQJDLTXOVEEFB-UHFFFAOYSA-N 1,2,3-benzothiadiazole Chemical group C1=CC=C2SN=NC2=C1 FNQJDLTXOVEEFB-UHFFFAOYSA-N 0.000 claims description 2
SLLFVLKNXABYGI-UHFFFAOYSA-N 1,2,3-benzoxadiazole Chemical group C1=CC=C2ON=NC2=C1 SLLFVLKNXABYGI-UHFFFAOYSA-N 0.000 claims description 2
KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical group C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 claims description 2
FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical group C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 claims description 2
BGDOLELXXPTPFX-UHFFFAOYSA-N 3,4-dihydro-2h-1,2-benzoxazine Chemical group C1=CC=C2ONCCC2=C1 BGDOLELXXPTPFX-UHFFFAOYSA-N 0.000 claims description 2
SQWZFLMPDUSYGV-UHFFFAOYSA-N 5-(6-quinoxalinylmethylidene)thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1=CC1=CC=C(N=CC=N2)C2=C1 SQWZFLMPDUSYGV-UHFFFAOYSA-N 0.000 claims description 2
ZFGAJYJQTCMPPX-UHFFFAOYSA-N 5-[(3-bromo-1-benzofuran-5-yl)methylidene]-1,3-thiazolidine-2,4-dione 5-[(2-bromo-3-methyl-1-benzofuran-5-yl)methylidene]-1,3-thiazolidine-2,4-dione Chemical compound BrC1=COC2=C1C=C(C=C2)C=C2C(NC(S2)=O)=O.BrC=2OC1=C(C2C)C=C(C=C1)C=C1C(NC(S1)=O)=O ZFGAJYJQTCMPPX-UHFFFAOYSA-N 0.000 claims description 2
MTPPLZXUSQABPA-UHFFFAOYSA-N 5-[[3-(furan-3-ylmethyl)benzimidazol-5-yl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1=CC1=CC=C(N=CN2CC3=COC=C3)C2=C1 MTPPLZXUSQABPA-UHFFFAOYSA-N 0.000 claims description 2
239000005964 Acibenzolar-S-methyl Chemical group 0.000 claims description 2
FJCFAMYYZBVETC-UHFFFAOYSA-N C(C#C)N1C=NC2=C1C=C(C=C2)C=C2C(NC(S2)=O)=O.C2(=CC=CC=C2)CCCCN2C=NC1=C2C=C(C=C1)C=C1C(NC(S1)=O)=O Chemical compound C(C#C)N1C=NC2=C1C=C(C=C2)C=C2C(NC(S2)=O)=O.C2(=CC=CC=C2)CCCCN2C=NC1=C2C=C(C=C1)C=C1C(NC(S1)=O)=O FJCFAMYYZBVETC-UHFFFAOYSA-N 0.000 claims description 2
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VMHIBFIGZHDNBP-UHFFFAOYSA-N COC1=CC(=CC2=C1OCO2)C=C2C(NC(S2)=O)=O.O2CCC1=C2C=CC(=C1)C=C1C(NC(S1)=O)=O Chemical compound COC1=CC(=CC2=C1OCO2)C=C2C(NC(S2)=O)=O.O2CCC1=C2C=CC(=C1)C=C1C(NC(S1)=O)=O VMHIBFIGZHDNBP-UHFFFAOYSA-N 0.000 claims description 2
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125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims description 2
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RDRCTBWRBXVSIY-UHFFFAOYSA-N tert-butyl 6-[(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]-1,4-benzoxazine-4-carboxylate Chemical compound C1=C2N(C(=O)OC(C)(C)C)C=COC2=CC=C1C=C1SC(=O)NC1=O RDRCTBWRBXVSIY-UHFFFAOYSA-N 0.000 claims description 2
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239000011975 tartaric acid Substances 0.000 description 1
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IACAHNBEKNUFKC-UHFFFAOYSA-N tert-butyl 6-[(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]-2,3-dihydro-1,4-benzoxazine-4-carboxylate Chemical compound C1=C2N(C(=O)OC(C)(C)C)CCOC2=CC=C1C=C1SC(=O)NC1=O IACAHNBEKNUFKC-UHFFFAOYSA-N 0.000 description 1
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230000001225 therapeutic effect Effects 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
150000003555 thioacetals Chemical class 0.000 description 1
XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical class CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
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238000012546 transfer Methods 0.000 description 1
102000027257 transmembrane receptors Human genes 0.000 description 1
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229910052721 tungsten Inorganic materials 0.000 description 1
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Classifications

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NO20050654A 2002-07-10 2005-02-08 Tizolidinon-vinylkondenserte benzenderivater, fremgangsmate for fremstilling derav og anvendelse derav for fremstilling av medikamenter og farmasoytisk sammensetning innholdende samme NO330862B1 (no)

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Application Number	Priority Date	Filing Date	Title
EP02100798		2002-07-10
US10/289,998 US20040092561A1 (en)	2002-11-07	2002-11-07	Azolidinone-vinyl fused -benzene derivatives
PCT/EP2003/050302 WO2004007491A1 (en)	2002-07-10	2003-07-10	Azolidinone-vinyl fused-benzene derivatives

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US (2)	US7846925B2 (sr)
EP (1)	EP1549644A1 (sr)
JP (2)	JP4782564B2 (sr)
CN (1)	CN1681811B (sr)
AU (1)	AU2003255528B2 (sr)
BR (2)	BR0312752A (sr)
CA (1)	CA2493843C (sr)
EA (1)	EA011807B1 (sr)
HR (1)	HRP20041207A2 (sr)
IL (1)	IL166202A (sr)
MX (1)	MXPA05000453A (sr)
NO (1)	NO330862B1 (sr)
PL (1)	PL374718A1 (sr)
RS (1)	RS115904A (sr)
WO (1)	WO2004007491A1 (sr)

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AU2003303231A1 (en) *	2002-12-20	2004-07-14	Warner-Lambert Company Llc	Benzoxazines and derivatives thereof as inhibitors of pi3ks
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WO2005082901A1 (en) *	2004-02-25	2005-09-09	Smithkline Beecham Corporation	Novel chemical compounds
WO2005100331A2 (en) *	2004-04-14	2005-10-27	Ranbaxy Laboratories Limited	Antidiabetic agents
EP1761540B1 (en)	2004-05-13	2016-09-28	Icos Corporation	Quinazolinones as inhibitors of human phosphatidylinositol 3-kinase delta
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US7846925B2 (en)	2010-12-07
IL166202A0 (en)	2006-01-15
CA2493843A1 (en)	2004-01-22
EA011807B1 (ru)	2009-06-30
PL374718A1 (en)	2005-10-31
EA200500143A1 (ru)	2005-08-25
HK1077068A1 (zh)	2006-02-03
MXPA05000453A (es)	2005-03-23
RS115904A (sr)	2006-12-15
JP4782564B2 (ja)	2011-09-28
CN1681811A (zh)	2005-10-12
US20090306069A1 (en)	2009-12-10
JP2005538188A (ja)	2005-12-15
BR0312752A (pt)	2005-04-26
CN1681811B (zh)	2010-05-26
US20060122176A1 (en)	2006-06-08
EP1549644A1 (en)	2005-07-06
CA2493843C (en)	2012-04-17
NO20050654L (no)	2005-03-15
JP2011116762A (ja)	2011-06-16
AU2003255528A1 (en)	2004-02-02
BR0312650A (pt)	2005-05-03
WO2004007491A1 (en)	2004-01-22
IL166202A (en)	2012-02-29
HRP20041207A2 (en)	2005-04-30
AU2003255528B2 (en)	2009-07-16

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