BG63695B1 - Бензонафтиридини като бронхиални лечебни средства - Google Patents

Бензонафтиридини като бронхиални лечебни средства Download PDF

Info

Publication number: BG63695B1
Authority: BG; Bulgaria
Prior art keywords: compounds; alkoxy; cis; methyl; naphthyridine
Prior art date: 1996-11-11

Application number

BG103310A

Other languages

Bulgarian (bg)

English (en)

Other versions

BG103310A (en

Inventor

Beate Gutterer

Hermann Amschler

Wolf-Ruediger Ulrich

Thomas Martin

Thomas Baer

Armin Hatzelmann

Karl Sanders

Rolf Beume

Hildegard Boss

Dietrich Haefner

Hans - Peter Kley

Karl-Josef Goebel

Dieter Flockerzi

Original Assignee

Byk Gulden Lomberg Chemische Fabrik Gmbh

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.)

1996-11-11

Filing date

1999-04-05

Publication date

2002-09-30

1999-04-05 Application filed by Byk Gulden Lomberg Chemische Fabrik Gmbh filed Critical Byk Gulden Lomberg Chemische Fabrik Gmbh

2000-05-31 Publication of BG103310A publication Critical patent/BG103310A/xx

2002-09-30 Publication of BG63695B1 publication Critical patent/BG63695B1/bg

Links

230000001225 therapeutic effect Effects 0.000 title abstract description 3
150000001875 compounds Chemical class 0.000 claims abstract description 112
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 138
-1 1-piperidyl Chemical group 0.000 claims description 90
125000003545 alkoxy group Chemical group 0.000 claims description 50
150000003839 salts Chemical class 0.000 claims description 41
230000003287 optical effect Effects 0.000 claims description 39
125000000217 alkyl group Chemical group 0.000 claims description 25
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 25
125000000000 cycloalkoxy group Chemical group 0.000 claims description 24
229910052739 hydrogen Inorganic materials 0.000 claims description 24
239000001257 hydrogen Substances 0.000 claims description 24
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 23
229910052731 fluorine Inorganic materials 0.000 claims description 18
239000011737 fluorine Substances 0.000 claims description 18
238000011282 treatment Methods 0.000 claims description 18
125000001153 fluoro group Chemical group F* 0.000 claims description 17
CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical group [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 14
125000000753 cycloalkyl group Chemical group 0.000 claims description 13
239000003814 drug Substances 0.000 claims description 12
229910052757 nitrogen Inorganic materials 0.000 claims description 12
238000002360 preparation method Methods 0.000 claims description 12
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 11
125000004433 nitrogen atom Chemical group N* 0.000 claims description 11
125000001424 substituent group Chemical group 0.000 claims description 11
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239000002773 nucleotide Substances 0.000 description 1
125000003729 nucleotide group Chemical group 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
125000005447 octyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
239000003921 oil Substances 0.000 description 1
239000003883 ointment base Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
201000008482 osteoarthritis Diseases 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
229940094443 oxytocics prostaglandins Drugs 0.000 description 1
230000020477 pH reduction Effects 0.000 description 1
210000003695 paranasal sinus Anatomy 0.000 description 1
244000045947 parasite Species 0.000 description 1
239000006072 paste Substances 0.000 description 1
230000035515 penetration Effects 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
210000003800 pharynx Anatomy 0.000 description 1
239000002570 phosphodiesterase III inhibitor Substances 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
150000003053 piperidines Chemical class 0.000 description 1
230000010118 platelet activation Effects 0.000 description 1
229920000137 polyphosphoric acid Polymers 0.000 description 1
150000007519 polyprotic acids Polymers 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000008569 process Effects 0.000 description 1
230000002062 proliferating effect Effects 0.000 description 1
JDHDNVYHHODZLJ-GOTSBHOMSA-N propan-2-yl 4-[[(3R,4S)-3-(3,4-diethoxyphenyl)-1-methylpiperidin-4-yl]carbamoyl]benzoate Chemical compound C(C)(C)OC(C1=CC=C(C(=O)N[C@@H]2[C@@H](CN(CC2)C)C2=CC(=C(C=C2)OCC)OCC)C=C1)=O JDHDNVYHHODZLJ-GOTSBHOMSA-N 0.000 description 1
RYTMPLWNLQTRKQ-SFTDATJTSA-N propan-2-yl 4-[[(3R,4S)-3-(3,4-dimethoxyphenyl)-1-methylpiperidin-4-yl]carbamoyl]benzoate Chemical compound C(C)(C)OC(C1=CC=C(C(=O)N[C@@H]2[C@@H](CN(CC2)C)C2=CC(=C(C=C2)OC)OC)C=C1)=O RYTMPLWNLQTRKQ-SFTDATJTSA-N 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
150000003180 prostaglandins Chemical class 0.000 description 1
230000002685 pulmonary effect Effects 0.000 description 1
208000002815 pulmonary hypertension Diseases 0.000 description 1
238000000746 purification Methods 0.000 description 1
125000003410 quininyl group Chemical group 0.000 description 1
239000000018 receptor agonist Substances 0.000 description 1
229940044601 receptor agonist Drugs 0.000 description 1
238000010992 reflux Methods 0.000 description 1
230000003578 releasing effect Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
230000029058 respiratory gaseous exchange Effects 0.000 description 1
206010039073 rheumatoid arthritis Diseases 0.000 description 1
206010039083 rhinitis Diseases 0.000 description 1
201000004700 rosacea Diseases 0.000 description 1
230000007017 scission Effects 0.000 description 1
208000008742 seborrheic dermatitis Diseases 0.000 description 1
238000000926 separation method Methods 0.000 description 1
230000036303 septic shock Effects 0.000 description 1
229940076279 serotonin Drugs 0.000 description 1
206010040560 shock Diseases 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
239000000050 smooth muscle relaxant Substances 0.000 description 1
239000003998 snake venom Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
239000007921 spray Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
230000000707 stereoselective effect Effects 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
238000003756 stirring Methods 0.000 description 1
239000000829 suppository Substances 0.000 description 1
230000001629 suppression Effects 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
230000002195 synergetic effect Effects 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
201000000596 systemic lupus erythematosus Diseases 0.000 description 1
239000003826 tablet Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
239000010936 titanium Substances 0.000 description 1
229910052719 titanium Inorganic materials 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
102000003390 tumor necrosis factor Human genes 0.000 description 1
210000000626 ureter Anatomy 0.000 description 1
210000001635 urinary tract Anatomy 0.000 description 1
230000002792 vascular Effects 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
238000005406 washing Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- 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
- A61P11/00—Drugs for disorders of the respiratory system
- 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
- A61P11/08—Bronchodilators
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Physical Education & Sports Medicine (AREA)
Pulmonology (AREA)
Neurology (AREA)
Biomedical Technology (AREA)
Cardiology (AREA)
Hematology (AREA)
Heart & Thoracic Surgery (AREA)
Neurosurgery (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Orthopedic Medicine & Surgery (AREA)
Immunology (AREA)
Diabetes (AREA)
Dermatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Pyrane Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Plural Heterocyclic Compounds (AREA)
Solid-Sorbent Or Filter-Aiding Compositions (AREA)

BG103310A 1996-11-11 1999-04-05 Бензонафтиридини като бронхиални лечебни средства BG63695B1 (bg)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
DE19646298		1996-11-11
EP96118188		1996-11-13
DE19739056		1997-09-05
PCT/EP1997/006096 WO1998021208A1 (en)	1996-11-11	1997-11-05	Benzonaphthyridines as bronchial therapeutics

Publications (2)

Publication Number	Publication Date
BG103310A BG103310A (en)	2000-05-31
BG63695B1 true BG63695B1 (bg)	2002-09-30

Family

ID=27216810

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
BG103310A BG63695B1 (bg)	1996-11-11	1999-04-05	Бензонафтиридини като бронхиални лечебни средства

Country Status (30)

Country	Link
US (1)	US6008215A (ja)
EP (1)	EP0937074B1 (ja)
JP (1)	JP4223075B2 (ja)
KR (1)	KR100484045B1 (ja)
CN (1)	CN1090188C (ja)
AT (1)	ATE234300T1 (ja)
AU (1)	AU733129B2 (ja)
BG (1)	BG63695B1 (ja)
BR (1)	BR9713338B1 (ja)
CA (1)	CA2270964C (ja)
CY (1)	CY2476B1 (ja)
CZ (1)	CZ288752B6 (ja)
DE (1)	DE69719778T2 (ja)
DK (1)	DK0937074T3 (ja)
EA (1)	EA001551B1 (ja)
EE (1)	EE03829B1 (ja)
ES (1)	ES2195189T3 (ja)
GE (1)	GEP20012390B (ja)
HU (1)	HU226981B1 (ja)
ID (1)	ID22042A (ja)
IL (1)	IL129054A (ja)
NO (1)	NO312764B1 (ja)
NZ (1)	NZ334976A (ja)
PL (1)	PL189641B1 (ja)
PT (1)	PT937074E (ja)
RS (1)	RS49607B (ja)
SI (1)	SI0937074T1 (ja)
SK (1)	SK283269B6 (ja)
TR (1)	TR199900856T2 (ja)
WO (1)	WO1998021208A1 (ja)

Families Citing this family (28)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ATE234301T1 (de)	1998-05-05	2003-03-15	Altana Pharma Ag	Neue benzonaphtyridin-n-oxide
EP1109810B1 (de)	1998-08-31	2004-06-16	ALTANA Pharma AG	Benzonaphthyridin-n-oxide mit pde3 und pde4 inhibierender aktivität
IT1303272B1 (it)	1998-10-29	2000-11-06	Zambon Spa	Derivati triciclici inibitori della fosfodiesterasi 4
CN1152864C (zh) *	1999-01-15	2004-06-09	奥坦纳医药公司	具有pde-iv抑制活性的苯基菲啶类化合物
EP1147087B1 (en) *	1999-01-15	2005-05-11	ALTANA Pharma AG	Phenanthridine-n-oxides with pde-iv inhibiting activity
EP1147103B1 (en)	1999-01-15	2005-05-04	ALTANA Pharma AG	Phenantrhridine-n-oxides with pde-iv inhibiting activity
WO2000042018A1 (en) *	1999-01-15	2000-07-20	Byk Gulden Lomberg Chemische Fabrik Gmbh	Polysubstituted 6-phenylphenanthridines with pde-iv inhibiting activity
EP1671651B1 (en) *	1999-08-21	2009-11-11	Nycomed GmbH	Synergistic combination of pumafentrine and salmeterol
NL1017973C2 (nl) *	2000-05-10	2002-11-08	Tristem Trading Cyprus Ltd	Inrichting.
WO2002066476A1 (en) *	2001-02-21	2002-08-29	Altana Pharma Ag	6-phenylbenzonaphthyridines
US6479493B1 (en)	2001-08-23	2002-11-12	Cell Pathways, Inc.	Methods for treatment of type I diabetes
EP1581533A2 (en) *	2002-08-17	2005-10-05	ALTANA Pharma AG	Novel benzonaphthyridines
HRP20050293A2 (en)	2002-09-04	2006-07-31	Altana Pharma Ag	Novel benzonaphthyridines
AU2003264132B2 (en) *	2002-09-04	2009-11-19	Takeda Gmbh	Novel benzonaphthyridines
WO2004087211A2 (en)	2003-04-01	2004-10-14	Applied Research Systems Ars Holding N.V.	Inhibitors of phosphodiesterases in infertility
AR049419A1 (es) *	2004-03-03	2006-08-02	Altana Pharma Ag	Hidroxi-6-fenilfenantridinas sustituidas con heterociclilo
HRP20130828T1 (en)	2004-03-03	2013-09-30	Takeda Gmbh	Novel hydroxy-6-heroarylphenanthridines and their use as pde4 inhibitors
AU2005221832A1 (en) *	2004-03-10	2005-09-22	Nycomed Gmbh	Novel amido-substituted hydroxy-6-phenylphenanthridines and their use as PDE4 inhibitors
US7671068B2 (en)	2004-03-17	2010-03-02	Nycomed Gmbh	N-(alkoxyalkyl) carbamoyl-substituted 6-phenyl-benzonaphthyridine derivatives and their use as PDE ¾ inhibitors
US7589205B2 (en)	2004-09-08	2009-09-15	Nycomed Gmbh	3-thia-10-aza-phenanthrene derivatives
US7838521B2 (en) *	2004-09-08	2010-11-23	Nycomed Gmbh	3-oxa-10-aza-phenanthrenes
MX2007010400A (es) *	2005-03-02	2008-01-11	Nycomed Gmbh	Nuevas sales de derivados de hexahidrofenantridina sustituida con 6-heterociclilo.
US20090221664A1 (en)	2005-10-19	2009-09-03	Abhijit Ray	Pharmaceutical compositions of muscarinic receptor antagonists
TW200808695A (en) *	2006-06-08	2008-02-16	Amgen Inc	Benzamide derivatives and uses related thereto
US7956064B2 (en) *	2006-09-01	2011-06-07	Cylene Pharmaceuticals, Inc.	Fused tricyclic compounds as serine-threonine protein kinase and PARP modulators
CA2722139C (en)	2008-04-23	2017-04-11	Rigel Pharmaceuticals, Inc.	Carboxamide compounds for the treatment of metabolic disorders
AR079451A1 (es)	2009-12-18	2012-01-25	Nycomed Gmbh	Compuestos 3,4,4a,10b-tetrahidro-1h-tiopirano[4,3-c]isoquinolina
CN108299429B (zh) *	2018-04-09	2021-10-08	中南大学	一类八氢苯并萘啶化合物及其制备方法和应用

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3899494A (en) *	1970-05-13	1975-08-12	Sandoz Ltd	Substituted 6-phenyl benzo-naphthyridines
EP0247971A3 (en) *	1986-05-29	1990-01-17	Sandoz Ag	Novel pharmaceutical compositions comprising and use of cis-6-(4-acetanilido)-8,9-dimethoxy-2-methyl-1,2,3,4,4a,10b-hexahydrobenzo[c][1,6]naphthyridin
MY105344A (en) *	1990-05-16	1994-09-30	Byk Gulden Lomberg Chemische Fabrik	New sulphonyl compounds

1997
- 1997-11-05 SI SI9730535T patent/SI0937074T1/xx unknown
- 1997-11-05 DK DK97950093T patent/DK0937074T3/da active
- 1997-11-05 ID IDW990180A patent/ID22042A/id unknown
- 1997-11-05 AU AU53170/98A patent/AU733129B2/en not_active Ceased
- 1997-11-05 EE EEP199900105A patent/EE03829B1/xx not_active IP Right Cessation
- 1997-11-05 KR KR10-1999-7004024A patent/KR100484045B1/ko not_active Expired - Fee Related
- 1997-11-05 CA CA002270964A patent/CA2270964C/en not_active Expired - Fee Related
- 1997-11-05 RS YUP-194/99A patent/RS49607B/sr unknown
- 1997-11-05 JP JP52212098A patent/JP4223075B2/ja not_active Expired - Fee Related
- 1997-11-05 TR TR1999/00856T patent/TR199900856T2/xx unknown
- 1997-11-05 BR BRPI9713338-8A patent/BR9713338B1/pt not_active IP Right Cessation
- 1997-11-05 GE GEAP19974710A patent/GEP20012390B/en unknown
- 1997-11-05 ES ES97950093T patent/ES2195189T3/es not_active Expired - Lifetime
- 1997-11-05 WO PCT/EP1997/006096 patent/WO1998021208A1/en not_active Ceased
- 1997-11-05 NZ NZ334976A patent/NZ334976A/xx not_active IP Right Cessation
- 1997-11-05 PT PT97950093T patent/PT937074E/pt unknown
- 1997-11-05 DE DE69719778T patent/DE69719778T2/de not_active Expired - Lifetime
- 1997-11-05 CZ CZ19991675A patent/CZ288752B6/cs not_active IP Right Cessation
- 1997-11-05 EP EP97950093A patent/EP0937074B1/en not_active Expired - Lifetime
- 1997-11-05 EA EA199900421A patent/EA001551B1/ru not_active IP Right Cessation
- 1997-11-05 SK SK623-99A patent/SK283269B6/sk not_active IP Right Cessation
- 1997-11-05 PL PL97333429A patent/PL189641B1/pl unknown
- 1997-11-05 US US09/284,458 patent/US6008215A/en not_active Expired - Lifetime
- 1997-11-05 CN CN97199529A patent/CN1090188C/zh not_active Expired - Fee Related
- 1997-11-05 HU HU0000426A patent/HU226981B1/hu not_active IP Right Cessation
- 1997-11-05 IL IL12905497A patent/IL129054A/en not_active IP Right Cessation
- 1997-11-05 AT AT97950093T patent/ATE234300T1/de active
1999
- 1999-04-05 BG BG103310A patent/BG63695B1/bg unknown
- 1999-05-11 NO NO19992282A patent/NO312764B1/no not_active IP Right Cessation
2004
- 2004-09-03 CY CY0400068A patent/CY2476B1/xx unknown

Also Published As

Publication number	Publication date
ID22042A (id)	1999-08-26
SK283269B6 (sk)	2003-04-01
NZ334976A (en)	2000-10-27
PL333429A1 (en)	1999-12-06
DK0937074T3 (da)	2003-06-23
HU226981B1 (hu)	2010-04-28
US6008215A (en)	1999-12-28
RS49607B (sr)	2007-06-04
NO992282D0 (no)	1999-05-11
BR9713338B1 (pt)	2009-12-01
CZ288752B6 (cs)	2001-08-15
JP4223075B2 (ja)	2009-02-12
EE03829B1 (et)	2002-08-15
IL129054A (en)	2002-07-25
KR100484045B1 (ko)	2005-04-20
CN1236367A (zh)	1999-11-24
KR20000053100A (ko)	2000-08-25
YU19499A (sh)	2001-09-28
NO992282L (no)	1999-05-11
HUP0000426A2 (hu)	2001-02-28
EP0937074B1 (en)	2003-03-12
HK1022151A1 (en)	2000-07-28
TR199900856T2 (xx)	1999-07-21
BG103310A (en)	2000-05-31
BR9713338A (pt)	2000-05-09
HUP0000426A3 (en)	2001-04-28
EE9900105A (et)	1999-10-15
AU733129B2 (en)	2001-05-10
GEP20012390B (en)	2001-03-25
ES2195189T3 (es)	2003-12-01
CZ167599A3 (cs)	1999-11-17
WO1998021208A1 (en)	1998-05-22
DE69719778T2 (de)	2004-02-05
CN1090188C (zh)	2002-09-04
EP0937074A1 (en)	1999-08-25
ATE234300T1 (de)	2003-03-15
IL129054A0 (en)	2000-02-17
CY2476B1 (en)	2005-05-03
PL189641B1 (pl)	2005-09-30
AU5317098A (en)	1998-06-03
NO312764B1 (no)	2002-07-01
DE69719778D1 (de)	2003-04-17
EA001551B1 (ru)	2001-04-23
JP2001503442A (ja)	2001-03-13
SK62399A3 (en)	1999-10-08
CA2270964A1 (en)	1998-05-22
EA199900421A1 (ru)	1999-10-28
CA2270964C (en)	2007-07-31
SI0937074T1 (en)	2003-08-31
PT937074E (pt)	2003-07-31

Publication	Publication Date	Title
BG63695B1 (bg)	2002-09-30	Бензонафтиридини като бронхиални лечебни средства
EP1075477B1 (de)	2003-03-12	Neue Benzonaphtyridin-N-oxide
EP1109810B1 (de)	2004-06-16	Benzonaphthyridin-n-oxide mit pde3 und pde4 inhibierender aktivität
DE69817548T2 (de)	2004-06-17	Tetrazole derivate
JP2002502403A (ja)	2002-01-22	ベンゾナフチリジン
JP2001510826A (ja)	2001-08-07	置換６−アルキルフェナントリジン
JP4248245B2 (ja)	2009-04-02	６−フェニルベンゾナフチリジン
JP4638736B2 (ja)	2011-02-23	新規のベンゾナフチリジン
HK1022151B (en)	2003-08-08	Benzonaphthyridines as bronchial therapeutics
MXPA99004345A (en)	2000-02-02	Benzonaphthyridines as bronchial therapeutics