NO329093B1 - Naftyridinderivater, deres fremstilling og deres anvendelse samt farmasoytisk sammensetning omfattende en slik forbindelse - Google Patents

Naftyridinderivater, deres fremstilling og deres anvendelse samt farmasoytisk sammensetning omfattende en slik forbindelse Download PDF

Info

Publication number: NO329093B1
Authority: NO; Norway
Prior art keywords: compound; alkoxy; group; compound according; naphthyridin
Prior art date: 2001-11-05

Application number

NO20042097A

Other languages

English (en)

Norwegian (no)

Other versions

NO20042097L (no

Inventor

Alastair Denholm

Thomas Hugo Keller

Clive Mccarthy

Original Assignee

Novartis Ag

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.)

2001-11-05

Filing date

2004-05-21

Publication date

2010-08-23

2001-11-05 Priority claimed from GB0126511A external-priority patent/GB0126511D0/en

2002-04-30 Priority claimed from GB0209882A external-priority patent/GB0209882D0/en

2004-05-21 Application filed by Novartis Ag filed Critical Novartis Ag

2004-05-21 Publication of NO20042097L publication Critical patent/NO20042097L/no

2010-08-23 Publication of NO329093B1 publication Critical patent/NO329093B1/no

Links

150000001875 compounds Chemical class 0.000 title claims description 82
238000002360 preparation method Methods 0.000 title claims description 6
239000008194 pharmaceutical composition Substances 0.000 title claims description 5
150000005054 naphthyridines Chemical class 0.000 title 1
238000011282 treatment Methods 0.000 claims description 41
150000003839 salts Chemical group 0.000 claims description 36
-1 4-[8-(5-fluoro-2-fluoro-2-methoxyphenyl)-[1,7]naphthyridin-6-yl]-cyclohexanecarboxylic acid Chemical compound 0.000 claims description 29
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 23
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
125000001424 substituent group Chemical group 0.000 claims description 19
239000003814 drug Substances 0.000 claims description 18
230000002757 inflammatory effect Effects 0.000 claims description 14
230000005764 inhibitory process Effects 0.000 claims description 13
101100296720 Dictyostelium discoideum Pde4 gene Proteins 0.000 claims description 12
101100082610 Plasmodium falciparum (isolate 3D7) PDEdelta gene Proteins 0.000 claims description 12
229910052736 halogen Inorganic materials 0.000 claims description 12
150000002367 halogens Chemical class 0.000 claims description 12
208000023504 respiratory system disease Diseases 0.000 claims description 12
230000000414 obstructive effect Effects 0.000 claims description 11
125000004093 cyano group Chemical group *C#N 0.000 claims description 10
108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 9
102100040247 Tumor necrosis factor Human genes 0.000 claims description 9
125000004432 carbon atom Chemical group C* 0.000 claims description 9
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 8
FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical group N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 claims description 8
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 8
ZHLTXMKVCCTAHU-UHFFFAOYSA-N ethyl 4-[8-(3-cyanophenyl)-1,7-naphthyridin-6-yl]cyclohexane-1-carboxylate Chemical compound C1CC(C(=O)OCC)CCC1C1=CC2=CC=CN=C2C(C=2C=C(C=CC=2)C#N)=N1 ZHLTXMKVCCTAHU-UHFFFAOYSA-N 0.000 claims description 8
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 7
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
125000005842 heteroatom Chemical group 0.000 claims description 7
125000000623 heterocyclic group Chemical group 0.000 claims description 7
208000027866 inflammatory disease Diseases 0.000 claims description 7
238000004519 manufacturing process Methods 0.000 claims description 7
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 6
125000006413 ring segment Chemical group 0.000 claims description 6
125000003118 aryl group Chemical group 0.000 claims description 5
125000004429 atom Chemical group 0.000 claims description 5
125000000753 cycloalkyl group Chemical group 0.000 claims description 4
239000003085 diluting agent Substances 0.000 claims description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
230000003828 downregulation Effects 0.000 claims description 3
230000001404 mediated effect Effects 0.000 claims description 3
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 2
JAZMOBNQGPEOPM-UHFFFAOYSA-N 4-[8-(3-carbamoylphenyl)-1,7-naphthyridin-6-yl]cyclohexane-1-carboxylic acid Chemical compound NC(=O)C1=CC=CC(C=2C3=NC=CC=C3C=C(N=2)C2CCC(CC2)C(O)=O)=C1 JAZMOBNQGPEOPM-UHFFFAOYSA-N 0.000 claims description 2
TWWNJXWEOLLKJT-UHFFFAOYSA-N 4-[8-(3-cyanophenyl)-1,7-naphthyridin-6-yl]cyclohexane-1-carboxylic acid Chemical compound C1CC(C(=O)O)CCC1C1=CC2=CC=CN=C2C(C=2C=C(C=CC=2)C#N)=N1 TWWNJXWEOLLKJT-UHFFFAOYSA-N 0.000 claims description 2
NBJPVPWHRDXZFE-UHFFFAOYSA-M potassium;4-[8-(3-cyanophenyl)-1,7-naphthyridin-6-yl]cyclohexane-1-carboxylate Chemical compound [K+].C1CC(C(=O)[O-])CCC1C1=CC2=CC=CN=C2C(C=2C=C(C=CC=2)C#N)=N1 NBJPVPWHRDXZFE-UHFFFAOYSA-M 0.000 claims description 2
BZTUWDYLJHYCFI-UHFFFAOYSA-M sodium;4-[8-(5-fluoro-2-methoxyphenyl)-1,7-naphthyridin-6-yl]cyclohexane-1-carboxylate Chemical compound [Na+].COC1=CC=C(F)C=C1C1=NC(C2CCC(CC2)C([O-])=O)=CC2=CC=CN=C12 BZTUWDYLJHYCFI-UHFFFAOYSA-M 0.000 claims description 2
DAKILIIJZBBNLO-UHFFFAOYSA-N 3-[6-(4-carboxycyclohexyl)-1,7-naphthyridin-8-yl]benzoic acid Chemical compound C1CC(C(=O)O)CCC1C1=CC2=CC=CN=C2C(C=2C=C(C=CC=2)C(O)=O)=N1 DAKILIIJZBBNLO-UHFFFAOYSA-N 0.000 claims 1
238000010511 deprotection reaction Methods 0.000 claims 1
GEBSAZQUXWFKCV-UHFFFAOYSA-N ethyl 4-[8-(5-fluoro-2-methoxyphenyl)-1,7-naphthyridin-6-yl]cyclohexane-1-carboxylate Chemical compound C1CC(C(=O)OCC)CCC1C1=CC2=CC=CN=C2C(C=2C(=CC=C(F)C=2)OC)=N1 GEBSAZQUXWFKCV-UHFFFAOYSA-N 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
239000000203 mixture Substances 0.000 description 43
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
239000003795 chemical substances by application Substances 0.000 description 23
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
208000006673 asthma Diseases 0.000 description 22
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
239000000243 solution Substances 0.000 description 21
238000000034 method Methods 0.000 description 19
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 17
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 15
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 15
239000000047 product Substances 0.000 description 15
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
238000006243 chemical reaction Methods 0.000 description 13
238000000746 purification Methods 0.000 description 13
239000010410 layer Substances 0.000 description 12
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
201000010099 disease Diseases 0.000 description 10
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
108010044467 Isoenzymes Proteins 0.000 description 9
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
229940079593 drug Drugs 0.000 description 9
238000009472 formulation Methods 0.000 description 9
AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 8
206010006895 Cachexia Diseases 0.000 description 8
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 8
239000002253 acid Substances 0.000 description 8
125000005843 halogen group Chemical group 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
239000012267 brine Substances 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 6
229940126062 Compound A Drugs 0.000 description 6
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
230000001154 acute effect Effects 0.000 description 6
238000004587 chromatography analysis Methods 0.000 description 6
239000012044 organic layer Substances 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
239000000741 silica gel Substances 0.000 description 6
229910002027 silica gel Inorganic materials 0.000 description 6
239000007787 solid Substances 0.000 description 6
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 6
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 5
102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 5
229910052786 argon Inorganic materials 0.000 description 5
239000000460 chlorine Substances 0.000 description 5
230000001684 chronic effect Effects 0.000 description 5
235000015165 citric acid Nutrition 0.000 description 5
239000000499 gel Substances 0.000 description 5
229910052943 magnesium sulfate Inorganic materials 0.000 description 5
235000019341 magnesium sulphate Nutrition 0.000 description 5
125000006239 protecting group Chemical group 0.000 description 5
239000011734 sodium Substances 0.000 description 5
239000011780 sodium chloride Substances 0.000 description 5
239000002904 solvent Substances 0.000 description 5
239000000126 substance Substances 0.000 description 5
MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 4
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 4
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
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206010040070 Septic Shock Diseases 0.000 description 4
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 4
125000003545 alkoxy group Chemical group 0.000 description 4
239000005557 antagonist Substances 0.000 description 4
230000003110 anti-inflammatory effect Effects 0.000 description 4
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125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 description 4
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 4
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 4
125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 4
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239000007858 starting material Substances 0.000 description 4
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NMPRJSCSBOKQRT-UHFFFAOYSA-N 4-[8-(5-fluoro-2-methoxyphenyl)-1,7-naphthyridin-6-yl]cyclohexane-1-carboxylic acid Chemical compound COC1=CC=C(F)C=C1C1=NC(C2CCC(CC2)C(O)=O)=CC2=CC=CN=C12 NMPRJSCSBOKQRT-UHFFFAOYSA-N 0.000 description 3
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101001098805 Homo sapiens cAMP-specific 3',5'-cyclic phosphodiesterase 4A Proteins 0.000 description 3
101000988424 Homo sapiens cAMP-specific 3',5'-cyclic phosphodiesterase 4B Proteins 0.000 description 3
101000988419 Homo sapiens cAMP-specific 3',5'-cyclic phosphodiesterase 4D Proteins 0.000 description 3
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PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
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IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 3
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NO20042097A 2001-11-05 2004-05-21 Naftyridinderivater, deres fremstilling og deres anvendelse samt farmasoytisk sammensetning omfattende en slik forbindelse NO329093B1 (no)

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Application Number	Priority Date	Filing Date	Title
GB0126511A GB0126511D0 (en)	2001-11-05	2001-11-05	Organic compounds
GB0209882A GB0209882D0 (en)	2002-04-30	2002-04-30	Organic compounds
PCT/EP2002/012300 WO2003039544A1 (en)	2001-11-05	2002-11-04	Naphtyridine derivatives, their preparation and their use as phosphodiesterase isoenzyme 4 (pde4) inhibitors

Publications (2)

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NO20042097L NO20042097L (no)	2004-05-21
NO329093B1 true NO329093B1 (no)	2010-08-23

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Country Status (25)

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US (1)	US7273875B2 (pt)
EP (1)	EP1443925B8 (pt)
JP (1)	JP4150672B2 (pt)
KR (1)	KR100623548B1 (pt)
CN (1)	CN1298324C (pt)
AR (1)	AR037517A1 (pt)
AT (1)	ATE349209T1 (pt)
BR (1)	BR0213877A (pt)
CA (1)	CA2462211C (pt)
CY (1)	CY1107532T1 (pt)
DE (1)	DE60217160T2 (pt)
DK (1)	DK1443925T3 (pt)
ES (1)	ES2275935T3 (pt)
HU (1)	HUP0402311A3 (pt)
IL (2)	IL161257A0 (pt)
MX (1)	MXPA04004264A (pt)
MY (1)	MY130622A (pt)
NO (1)	NO329093B1 (pt)
NZ (1)	NZ532586A (pt)
PE (1)	PE20030535A1 (pt)
PL (1)	PL368286A1 (pt)
PT (1)	PT1443925E (pt)
RU (1)	RU2296764C2 (pt)
TW (1)	TWI320784B (pt)
WO (1)	WO2003039544A1 (pt)

Families Citing this family (77)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ES2211344B1 (es) *	2002-12-26	2005-10-01	Almirall Prodesfarma, S.A.	Nuevos derivados de piridazin-3(2h)-ona.
AR044519A1 (es)	2003-05-02	2005-09-14	Novartis Ag	Derivados de piridin-tiazol amina y de pirimidin-tiazol amina
GB0401334D0 (en)	2004-01-21	2004-02-25	Novartis Ag	Organic compounds
GB0411056D0 (en)	2004-05-18	2004-06-23	Novartis Ag	Organic compounds
ES2251866B1 (es) *	2004-06-18	2007-06-16	Laboratorios Almirall S.A.	Nuevos derivados de piridazin-3(2h)-ona.
ES2251867B1 (es) *	2004-06-21	2007-06-16	Laboratorios Almirall S.A.	Nuevos derivados de piridazin-3(2h)-ona.
GT200500281A (es)	2004-10-22	2006-04-24	Novartis Ag	Compuestos organicos.
GB0424284D0 (en)	2004-11-02	2004-12-01	Novartis Ag	Organic compounds
GB0426164D0 (en)	2004-11-29	2004-12-29	Novartis Ag	Organic compounds
GB0507577D0 (en)	2005-04-14	2005-05-18	Novartis Ag	Organic compounds
GB0510390D0 (en)	2005-05-20	2005-06-29	Novartis Ag	Organic compounds
WO2007045477A2 (en)	2005-10-21	2007-04-26	Novartis Ag	Human antibodies against il-13 and therapeutic uses
GB0526244D0 (en)	2005-12-22	2006-02-01	Novartis Ag	Organic compounds
GB0601951D0 (en) *	2006-01-31	2006-03-15	Novartis Ag	Organic compounds
PT2322525E (pt)	2006-04-21	2013-12-26	Novartis Ag	Derivados de purina para utilização como agonistas do recetor de adenosina a2a
WO2008037477A1 (en)	2006-09-29	2008-04-03	Novartis Ag	Pyrazolopyrimidines as p13k lipid kinase inhibitors
JP2010508315A (ja)	2006-10-30	2010-03-18	ノバルティスアーゲー	抗炎症剤としてのヘテロ環式化合物
RS51644B (sr)	2007-01-10	2011-10-31	Irm Llc.	Jedinjenja i preparati kao inhibitori kanal aktivirajuće proteaze
ES2320954B1 (es) *	2007-03-02	2010-03-16	Laboratorio Almirall S.A.	Nuevo procedimiento de preparacion de 3-metil-4-fenilisoxazolo (3,4-d)iridazin-7(6h)-ona.
CN101687851B (zh)	2007-05-07	2013-02-27	诺瓦提斯公司	有机化合物
WO2009013286A1 (en) *	2007-07-24	2009-01-29	Novartis Ag	Organic compounds
CL2008003651A1 (es)	2007-12-10	2009-06-19	Novartis Ag	Compuestos derivados de 3,5-diamino-6-cloropirazinamida sustituida; composicion farmaceutica; combinacion farmaceutica; y uso en el tratamiento de una condición inflamatoria o alergica, en particular una enfermedad inflamatoria u obstructiva de las vias respiratorias.
AU2009203693B2 (en)	2008-01-11	2012-06-07	Novartis Ag	Pyrimidines as kinase inhibitors
US8268834B2 (en)	2008-03-19	2012-09-18	Novartis Ag	Pyrazine derivatives that inhibit phosphatidylinositol 3-kinase enzyme
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PL2391366T3 (pl)	2009-01-29	2013-04-30	Novartis Ag	Podstawione benzimidazole do leczenia gwiaździaków
US8389526B2 (en)	2009-08-07	2013-03-05	Novartis Ag	3-heteroarylmethyl-imidazo[1,2-b]pyridazin-6-yl derivatives
EA201200260A1 (ru)	2009-08-12	2012-09-28	Новартис Аг	Гетероциклические гидразоны и их применение для лечения рака и воспаления
NZ598220A (en)	2009-08-17	2014-02-28	Intellikine Llc	Heterocyclic compounds and uses thereof
CA2771432A1 (en)	2009-08-20	2011-02-24	Novartis Ag	Heterocyclic oxime compounds
CN102548536A (zh) *	2009-10-01	2012-07-04	爱尔康研究有限公司	奥洛他定组合物及其用途
US20110098311A1 (en)	2009-10-22	2011-04-28	Vertex Pharmaceuticals Incorported	Compositions for treatment of cystic fibrosis and other chronic diseases
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UY33597A (es)	2010-09-09	2012-04-30	Irm Llc	Compuestos y composiciones como inhibidores de la trk
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US8372845B2 (en)	2010-09-17	2013-02-12	Novartis Ag	Pyrazine derivatives as enac blockers
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WO2012116237A2 (en)	2011-02-23	2012-08-30	Intellikine, Llc	Heterocyclic compounds and uses thereof
MA34969B1 (fr)	2011-02-25	2014-03-01	Irm Llc	Composes et compositions en tant qu inibiteurs de trk
TW201311149A (zh) *	2011-06-24	2013-03-16	Ishihara Sangyo Kaisha	有害生物防治劑
US8883819B2 (en)	2011-09-01	2014-11-11	Irm Llc	Bicyclic heterocycle derivatives for the treatment of pulmonary arterial hypertension
CA2848809A1 (en)	2011-09-15	2013-03-21	Novartis Ag	6-substituted 3-(quinolin-6-ylthio)-[1,2,4]triazolo[4,3-a]pyradines as c-met tyrosine kinase
ES2882807T3 (es)	2011-09-16	2021-12-02	Novartis Ag	Heterociclil carboxamidas N-sustituidas
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WO2013038373A1 (en)	2011-09-16	2013-03-21	Novartis Ag	Pyridine amide derivatives
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WO2013038381A1 (en)	2011-09-16	2013-03-21	Novartis Ag	Pyridine/pyrazine amide derivatives
JP6130391B2 (ja)	2011-11-23	2017-05-17	インテリカイン，エルエルシー	Ｍｔｏｒ阻害剤を使用する強化された治療レジメン
UY34572A (es)	2012-01-13	2013-09-02	Novartis Ag	Compuestos heterocíclicos agonistas del receptor ip
US8809340B2 (en)	2012-03-19	2014-08-19	Novartis Ag	Crystalline form
AU2013243097A1 (en)	2012-04-03	2014-10-09	Novartis Ag	Combination products with tyrosine kinase inhibitors and their use
CN103969300B (zh) *	2013-01-24	2016-08-17	湖北大学	一种识别cgg三核苷酸重复序列的双功能电活性探针、探针的制备及试剂盒
CN105189500A (zh)	2013-02-13	2015-12-23	诺华股份有限公司	Ip受体激动剂杂环化合物
BR112015019276A2 (pt)	2013-02-19	2017-07-18	Pfizer	compostos de azabenzimidazol como inibidores de isoenzimas de pde4 para o tratamento de distúrbios do snc e outros distúrbios
US9073921B2 (en)	2013-03-01	2015-07-07	Novartis Ag	Salt forms of bicyclic heterocyclic derivatives
JP6282721B2 (ja)	2013-03-14	2018-02-21	ダート・ニューロサイエンス・（ケイマン）・リミテッド	Ｐｄｅ４阻害剤としての置換ピリジン及びピラジン化合物
EP2968340A4 (en)	2013-03-15	2016-08-10	Intellikine Llc	COMBINING KINASE INHIBITORS AND USES THEREOF
GB201305668D0 (en)	2013-03-28	2013-05-15	Glaxosmithkline Ip Dev Ltd	Avs6 Integrin Antagonists
TW201605450A (zh)	2013-12-03	2016-02-16	諾華公司	Ｍｄｍ２抑制劑與ＢＲＡＦ抑制劑之組合及其用途
CA2945212A1 (en)	2014-04-24	2015-10-29	Novartis Ag	Amino pyrazine derivatives as phosphatidylinositol 3-kinase inhibitors
US9862711B2 (en)	2014-04-24	2018-01-09	Novartis Ag	Pyrazine derivatives as phosphatidylinositol 3-kinase inhibitors
BR112016024484A2 (pt)	2014-04-24	2017-08-15	Novartis Ag	derivados de aminopiridina como inibidores de fosfatidilinositol 3-quinase
WO2016012896A1 (en)	2014-07-24	2016-01-28	Pfizer Inc.	Pyrazolopyrimidine compounds
WO2016011658A1 (en)	2014-07-25	2016-01-28	Novartis Ag	Combination therapy
CA2954862A1 (en)	2014-07-31	2016-02-04	Novartis Ag	Combination therapy
MD20170011A2 (ro)	2014-08-06	2017-08-31	Pfizer Inc.	Compuşi imidazopiridazinici
GB201417002D0 (en)	2014-09-26	2014-11-12	Glaxosmithkline Ip Dev Ltd	Novel compound
GB201417094D0 (en) *	2014-09-26	2014-11-12	Glaxosmithkline Ip Dev Ltd	Novel compounds
CN106146491B (zh) *	2015-03-27	2017-12-12	沈阳三生制药有限责任公司	被芳基或杂芳基取代的5‑羟基‑1,7‑萘啶化合物、其制备方法及其制药用途
GB201604680D0 (en)	2016-03-21	2016-05-04	Glaxosmithkline Ip Dev Ltd	Chemical Compounds
WO2020139830A2 (en)	2018-12-28	2020-07-02	Regeneron Pharmaceuticals, Inc.	Treatment of respiratory disorders with arachidonate15-lipoxygenase (alox15) inhibitors
AU2020290094B2 (en)	2019-06-10	2024-01-18	Novartis Ag	Pyridine and pyrazine derivative for the treatment of CF, COPD, and bronchiectasis
CN110339192A (zh) *	2019-08-22	2019-10-18	吉林大学	一种掌叶防己碱用于治疗急性肺损伤的实验方法
AU2020338971B2 (en)	2019-08-28	2023-11-23	Novartis Ag	Substituted 1,3-phenyl heteroaryl derivatives and their use in the treatment of disease
EP3805206A1 (en) *	2019-10-08	2021-04-14	Novaled GmbH	Compound and an organic semiconducting layer, an organic electronic device, a display device and a lighting device comprising the same
TW202140550A (zh)	2020-01-29	2021-11-01	瑞士商諾華公司	使用抗ｔｓｌｐ抗體治療炎性或阻塞性氣道疾病之方法

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB8800397D0 (en) *	1988-01-08	1988-02-10	Sandoz Ltd	Improvements in/relating to organic compounds
IE903911A1 (en) *	1989-11-20	1991-05-22	Ici Plc	Diazine derivatives
US5466697A (en) *	1994-07-13	1995-11-14	Syntex (U.S.A.) Inc.	8-phenyl-1,6-naphthyridin-5-ones
GB9622386D0 (en) *	1996-10-28	1997-01-08	Sandoz Ltd	Organic compounds
RU2174123C2 (ru) *	1996-10-28	2001-09-27	Новартис Аг	Производные 8-арил-1,7-нафтиридина и фармацевтическая композиция, обладающая противовоспалительной активностью
ATE404539T1 (de)	1997-10-02	2008-08-15	Eisai R&D Man Co Ltd	Kondensierte pyridinderivate
JP2002114684A (ja)	2000-10-03	2002-04-16	Eisai Co Ltd	尿路疾患治療剤

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- 2002-11-01 AR ARP020104187A patent/AR037517A1/es unknown
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- 2002-11-04 EP EP02787554A patent/EP1443925B8/en not_active Expired - Lifetime
- 2002-11-04 DE DE60217160T patent/DE60217160T2/de not_active Expired - Lifetime
- 2002-11-04 CN CNB028214897A patent/CN1298324C/zh not_active Expired - Lifetime
- 2002-11-04 DK DK02787554T patent/DK1443925T3/da active
- 2002-11-04 HU HU0402311A patent/HUP0402311A3/hu unknown
- 2002-11-04 TW TW091132476A patent/TWI320784B/zh not_active IP Right Cessation
- 2002-11-04 KR KR1020047006772A patent/KR100623548B1/ko not_active Expired - Fee Related
- 2002-11-04 US US10/494,223 patent/US7273875B2/en not_active Expired - Lifetime
- 2002-11-04 PL PL02368286A patent/PL368286A1/xx not_active Application Discontinuation
- 2002-11-04 BR BR0213877-8A patent/BR0213877A/pt not_active Application Discontinuation
- 2002-11-04 PE PE2002001073A patent/PE20030535A1/es not_active Application Discontinuation
- 2002-11-04 MX MXPA04004264A patent/MXPA04004264A/es active IP Right Grant
- 2002-11-04 JP JP2003541835A patent/JP4150672B2/ja not_active Expired - Lifetime
- 2002-11-04 RU RU2004117169/04A patent/RU2296764C2/ru not_active IP Right Cessation
- 2002-11-04 AT AT02787554T patent/ATE349209T1/de active
- 2002-11-04 ES ES02787554T patent/ES2275935T3/es not_active Expired - Lifetime
- 2002-11-04 NZ NZ532586A patent/NZ532586A/en not_active IP Right Cessation
- 2002-11-04 WO PCT/EP2002/012300 patent/WO2003039544A1/en not_active Ceased
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- 2002-11-04 IL IL16125702A patent/IL161257A0/xx unknown
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2004
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- 2004-05-21 NO NO20042097A patent/NO329093B1/no not_active IP Right Cessation
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CA2462211A1 (en)	2003-05-15
CY1107532T1 (el)	2013-03-13
RU2004117169A (ru)	2006-01-10
DK1443925T3 (da)	2007-03-19
EP1443925A1 (en)	2004-08-11
HUP0402311A2 (hu)	2005-02-28
MXPA04004264A (es)	2005-07-05
IL161257A0 (en)	2004-09-27
WO2003039544A1 (en)	2003-05-15
KR20040063133A (ko)	2004-07-12
NO20042097L (no)	2004-05-21
CN1578661A (zh)	2005-02-09
CA2462211C (en)	2011-03-29
US20040254212A1 (en)	2004-12-16
EP1443925B1 (en)	2006-12-27
US7273875B2 (en)	2007-09-25
RU2296764C2 (ru)	2007-04-10
AR037517A1 (es)	2004-11-17
JP2005507947A (ja)	2005-03-24
PL368286A1 (en)	2005-03-21
IL161257A (en)	2010-12-30
DE60217160T2 (de)	2007-10-04
HK1069970A1 (en)	2005-06-10
CN1298324C (zh)	2007-02-07
PE20030535A1 (es)	2003-07-11
DE60217160D1 (de)	2007-02-08
BR0213877A (pt)	2004-08-31
TWI320784B (en)	2010-02-21
EP1443925B8 (en)	2007-02-28
TW200300141A (en)	2003-05-16
NZ532586A (en)	2005-12-23
HUP0402311A3 (en)	2012-03-28
ATE349209T1 (de)	2007-01-15
MY130622A (en)	2007-07-31
ES2275935T3 (es)	2007-06-16
KR100623548B1 (ko)	2006-09-19
JP4150672B2 (ja)	2008-09-17
PT1443925E (pt)	2007-03-30

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2012-06-25	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
NO329093B1 (no)	2010-08-23	Naftyridinderivater, deres fremstilling og deres anvendelse samt farmasoytisk sammensetning omfattende en slik forbindelse
CA2569125C (en)	2013-01-08	Pyrrolopyridine derivatives and their use as crth2 antagonists
US8431703B2 (en)	2013-04-30	Pyrrolopyridine compounds and their use in treating disease
SK1942001A3 (en)	2001-12-03	1h-imidazopyridine derivatives
HUP0004422A2 (hu)	2001-04-28	2-Aril-8-oxohidropurin-származékok, eljárás előállításukra, ilyen vegyületeket tartalmazó gyógyászati készítmények
EP2139881B1 (en)	2011-11-09	Quinolines and their therapeutic use
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