SK3242000A3 - Pyrrolopyrrolone derivatives as inhibitors of neutrophil elastase - Google Patents

Pyrrolopyrrolone derivatives as inhibitors of neutrophil elastase Download PDF

Info

Publication number: SK3242000A3
Authority: SK; Slovakia
Prior art keywords: formula; compound; pyrrolopyrrone; isopropyl; derivatives
Prior art date: 1997-09-09

Application number

SK324-2000A

Other languages

English (en)

Slovak (sk)

Inventor

Michael Dennis Dowle

Harry Finch

Lee Andrew Harrison

Graham George Adam Inglis

Martin Redpath Johnson

Simon John Macdonald

Original Assignee

Glaxo Group Ltd

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.)

1997-09-09

Filing date

1998-09-07

Publication date

2001-03-12

1998-09-07 Application filed by Glaxo Group Ltd filed Critical Glaxo Group Ltd

2001-03-12 Publication of SK3242000A3 publication Critical patent/SK3242000A3/sk

Links

108010028275 Leukocyte Elastase Proteins 0.000 title description 5
102000016799 Leukocyte elastase Human genes 0.000 title description 5
239000003112 inhibitor Substances 0.000 title description 5
ACJSMQZKXAMMRA-UHFFFAOYSA-N 1h-pyrrolo[3,2-b]pyrrol-5-one Chemical class N1C=CC2=NC(=O)C=C21 ACJSMQZKXAMMRA-UHFFFAOYSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 132
238000000034 method Methods 0.000 claims description 32
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 27
125000000217 alkyl group Chemical group 0.000 claims description 22
150000003839 salts Chemical class 0.000 claims description 22
125000006239 protecting group Chemical group 0.000 claims description 21
-1 1-benzylazetidine-3-carbonyl Chemical group 0.000 claims description 20
239000000203 mixture Substances 0.000 claims description 20
239000002253 acid Substances 0.000 claims description 17
238000002360 preparation method Methods 0.000 claims description 15
239000008194 pharmaceutical composition Substances 0.000 claims description 12
206010006451 bronchitis Diseases 0.000 claims description 11
230000008569 process Effects 0.000 claims description 11
239000012453 solvate Substances 0.000 claims description 11
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
206010006458 Bronchitis chronic Diseases 0.000 claims description 8
125000004432 carbon atom Chemical group C* 0.000 claims description 8
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
208000007451 chronic bronchitis Diseases 0.000 claims description 8
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
239000003814 drug Substances 0.000 claims description 7
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 6
239000012458 free base Substances 0.000 claims description 6
125000005843 halogen group Chemical group 0.000 claims description 6
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 5
150000002148 esters Chemical class 0.000 claims description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
150000004820 halides Chemical class 0.000 claims description 5
238000004519 manufacturing process Methods 0.000 claims description 5
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
229910052801 chlorine Inorganic materials 0.000 claims description 4
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
238000006268 reductive amination reaction Methods 0.000 claims description 4
229910052717 sulfur Inorganic materials 0.000 claims description 4
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
208000006673 asthma Diseases 0.000 claims description 3
125000004434 sulfur atom Chemical group 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
125000003342 alkenyl group Chemical group 0.000 claims description 2
125000001309 chloro group Chemical group Cl* 0.000 claims description 2
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
239000003085 diluting agent Substances 0.000 claims description 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
230000001590 oxidative effect Effects 0.000 claims description 2
VIXWGKYSYIBATJ-UHFFFAOYSA-N pyrrol-2-one Chemical compound O=C1C=CC=N1 VIXWGKYSYIBATJ-UHFFFAOYSA-N 0.000 claims description 2
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
XKEFTOLYQVJIJM-UHFFFAOYSA-N 4-methylsulfonyl-1,2,3,3a,6,6a-hexahydropyrrolo[3,2-b]pyrrol-5-one Chemical compound C1CNC2CC(=O)N(S(=O)(=O)C)C21 XKEFTOLYQVJIJM-UHFFFAOYSA-N 0.000 claims 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
230000002378 acidificating effect Effects 0.000 claims 1
239000011593 sulfur Substances 0.000 claims 1
FEACDYATMHKJPE-JXHOJRNMSA-N xxxx-3 Chemical compound C1CC(C)CC(OC)C(O)C(C)\C=C(C)\C(OC(N)=O)C(OC)CC\C=C(C)\C(=O)NC2=CC(O)=C(O)C1=C2 FEACDYATMHKJPE-JXHOJRNMSA-N 0.000 claims 1
208000027866 inflammatory disease Diseases 0.000 abstract description 2
210000002345 respiratory system Anatomy 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 68
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
239000000543 intermediate Substances 0.000 description 44
239000002904 solvent Substances 0.000 description 35
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
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OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
239000002585 base Substances 0.000 description 20
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
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201000010099 disease Diseases 0.000 description 13
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 13
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
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238000004809 thin layer chromatography Methods 0.000 description 11
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
230000000694 effects Effects 0.000 description 10
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
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SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
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ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 9
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 9
229910000041 hydrogen chloride Inorganic materials 0.000 description 9
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 9
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102000004190 Enzymes Human genes 0.000 description 8
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ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
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239000000284 extract Substances 0.000 description 8
YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 8
229910052757 nitrogen Inorganic materials 0.000 description 8
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239000012442 inert solvent Substances 0.000 description 7
210000004072 lung Anatomy 0.000 description 7
210000000440 neutrophil Anatomy 0.000 description 7
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—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
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
- A—HUMAN NECESSITIES
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- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
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- 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
- 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
- A61P7/08—Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/04—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Veterinary Medicine (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
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Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Engineering & Computer Science (AREA)
Pulmonology (AREA)
Dermatology (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Hematology (AREA)
Vascular Medicine (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Urology & Nephrology (AREA)
Diabetes (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Hydrogenated Pyridines (AREA)

SK324-2000A 1997-09-09 1998-09-07 Pyrrolopyrrolone derivatives as inhibitors of neutrophil elastase SK3242000A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB9719187.8A GB9719187D0 (en)	1997-09-09	1997-09-09	Compounds
PCT/EP1998/005604 WO1999012931A1 (en)	1997-09-09	1998-09-07	Pyrrolopyrrolone derivatives as inhibitors of neutrophil elastase

Publications (1)

Publication Number	Publication Date
SK3242000A3 true SK3242000A3 (en)	2001-03-12

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ID=10818820

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Application Number	Title	Priority Date	Filing Date
SK324-2000A SK3242000A3 (en)	1997-09-09	1998-09-07	Pyrrolopyrrolone derivatives as inhibitors of neutrophil elastase

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US (1)	US6228853B1 (tr)
EP (1)	EP1019406A1 (tr)
JP (1)	JP2001515902A (tr)
KR (1)	KR20010023830A (tr)
CN (1)	CN1278821A (tr)
AP (1)	AP2000001760A0 (tr)
AU (1)	AU9536098A (tr)
BR (1)	BR9811651A (tr)
CA (1)	CA2303249A1 (tr)
EA (1)	EA200000205A1 (tr)
EE (1)	EE200000137A (tr)
GB (1)	GB9719187D0 (tr)
HR (1)	HRP20000136A2 (tr)
HU (1)	HUP0003475A3 (tr)
ID (1)	ID24364A (tr)
IL (1)	IL134935A0 (tr)
IS (1)	IS5394A (tr)
MA (1)	MA26544A1 (tr)
NO (1)	NO20001200L (tr)
PL (1)	PL339186A1 (tr)
SK (1)	SK3242000A3 (tr)
TR (1)	TR200001026T2 (tr)
WO (1)	WO1999012931A1 (tr)
ZA (1)	ZA988162B (tr)

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FR2805818B1 (fr) *	2000-03-03	2002-04-26	Aventis Pharma Sa	Derives d'azetidine, leur preparation et les compositions pharmaceutiques les contenant
US7745226B2 (en) *	2005-04-06	2010-06-29	Quest Diagnostics Investments Incorporated	Methods for detecting vitamin D metabolites
US7972868B2 (en)	2007-11-28	2011-07-05	Quest Diagnostics Investments Incorporated	Methods for detecting dihydroxyvitamin D metabolites by mass spectrometry
US7977117B2 (en)	2009-12-03	2011-07-12	Quest Diagnostics Investments Incorprated	Vitamin D metabolite determination utilizing mass spectrometry following derivatization
JP5739903B2 (ja)	2009-12-11	2015-06-24	クエストダイアグノスティックスインヴェストメンツインコーポレイテッド	複合試料中のステロイド化合物の質量分析
CN102753964A (zh)	2009-12-11	2012-10-24	奎斯特诊断投资公司	非衍生的、非代谢的维生素d的质谱测定
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1998
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- 1998-09-07 ID IDW20000665A patent/ID24364A/id unknown
- 1998-09-07 WO PCT/EP1998/005604 patent/WO1999012931A1/en not_active Ceased
- 1998-09-07 SK SK324-2000A patent/SK3242000A3/sk unknown
- 1998-09-07 AP APAP/P/2000/001760A patent/AP2000001760A0/en unknown
- 1998-09-07 JP JP2000510738A patent/JP2001515902A/ja active Pending
- 1998-09-07 MA MA25244A patent/MA26544A1/fr unknown
- 1998-09-07 IL IL13493598A patent/IL134935A0/xx unknown
- 1998-09-07 HU HU0003475A patent/HUP0003475A3/hu unknown
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- 1998-09-07 CA CA002303249A patent/CA2303249A1/en not_active Abandoned
- 1998-09-07 BR BR9811651-7A patent/BR9811651A/pt not_active Application Discontinuation
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- 1998-09-07 CN CN98810967A patent/CN1278821A/zh active Pending
- 1998-09-07 EA EA200000205A patent/EA200000205A1/ru unknown
- 1998-09-07 KR KR1020007002505A patent/KR20010023830A/ko not_active Withdrawn
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- 1998-09-07 US US09/508,326 patent/US6228853B1/en not_active Expired - Fee Related
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2000
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- 2000-03-08 NO NO20001200A patent/NO20001200L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
NO20001200D0 (no)	2000-03-08
MA26544A1 (fr)	2004-12-20
HRP20000136A2 (en)	2000-08-31
JP2001515902A (ja)	2001-09-25
US6228853B1 (en)	2001-05-08
CN1278821A (zh)	2001-01-03
CA2303249A1 (en)	1999-03-18
ID24364A (id)	2000-07-13
EA200000205A1 (ru)	2000-10-30
NO20001200L (no)	2000-05-08
EE200000137A (et)	2001-02-15
BR9811651A (pt)	2000-08-08
KR20010023830A (ko)	2001-03-26
WO1999012931A1 (en)	1999-03-18
PL339186A1 (en)	2000-12-04
AU9536098A (en)	1999-03-29
EP1019406A1 (en)	2000-07-19
ZA988162B (en)	2000-03-22
IS5394A (is)	2000-03-03
AP2000001760A0 (en)	2000-03-31
HUP0003475A3 (en)	2002-01-28
IL134935A0 (en)	2001-05-20
TR200001026T2 (tr)	2000-09-21
HUP0003475A2 (hu)	2001-09-28
GB9719187D0 (en)	1997-11-12

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