CA2024071C - Pyrido[2,3-b][1,5]benzoxazepine (et -thiazepine)-5(6h)-ones et -thiones et leur utilisation pour la prevention et le traitement des infections a hiv - Google Patents

Pyrido[2,3-b][1,5]benzoxazepine (et -thiazepine)-5(6h)-ones et -thiones et leur utilisation pour la prevention et le traitement des infections a hiv Download PDF

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Publication number: CA2024071C
Authority: CA; Canada
Prior art keywords: carbon atoms; hydrogen; formula; amino; compound
Prior art date: 1989-08-29
Legal status (The legal status 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 status listed.): Expired - Fee Related

Application number

CA002024071A

Other languages

English (en)

Other versions

CA2024071A1 (fr

Inventor

Karl D. Hargrave

Gunther Schmidt (Deceased)

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Boehringer Ingelheim Pharma GmbH and Co KG

Boehringer Ingelheim Pharmaceuticals Inc

Original Assignee

Dr Karl Thomae GmbH

Boehringer Ingelheim Pharmaceuticals Inc

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.)

1989-08-29

Filing date

1990-08-27

Publication date

2002-06-04

1990-08-27 Application filed by Dr Karl Thomae GmbH, Boehringer Ingelheim Pharmaceuticals Inc filed Critical Dr Karl Thomae GmbH

1991-03-01 Publication of CA2024071A1 publication Critical patent/CA2024071A1/fr

2002-06-04 Application granted granted Critical

2002-06-04 Publication of CA2024071C publication Critical patent/CA2024071C/fr

2010-08-27 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

230000002265 prevention Effects 0.000 title claims abstract description 6
208000031886 HIV Infections Diseases 0.000 title claims description 6
SSAZFIRSEATBMQ-UHFFFAOYSA-N pyrido[2,3-b][1,5]benzoxazepine Chemical compound N1=CC2=CC=CN=C2OC2=CC=CC=C21 SSAZFIRSEATBMQ-UHFFFAOYSA-N 0.000 title abstract description 4
208000037357 HIV infectious disease Diseases 0.000 title description 2
208000033519 human immunodeficiency virus infectious disease Diseases 0.000 title description 2
125000004432 carbon atom Chemical group C* 0.000 claims description 145
150000001875 compounds Chemical class 0.000 claims description 71
239000001257 hydrogen Substances 0.000 claims description 48
229910052739 hydrogen Inorganic materials 0.000 claims description 48
125000000217 alkyl group Chemical group 0.000 claims description 45
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 42
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 31
238000000034 method Methods 0.000 claims description 22
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 21
239000001301 oxygen Substances 0.000 claims description 21
229910052760 oxygen Inorganic materials 0.000 claims description 21
-1 aminocarbonylmethyl Chemical group 0.000 claims description 18
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 17
125000001309 chloro group Chemical group Cl* 0.000 claims description 16
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 15
125000006350 alkyl thio alkyl group Chemical group 0.000 claims description 15
229910052717 sulfur Chemical group 0.000 claims description 15
239000011593 sulfur Chemical group 0.000 claims description 15
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 13
125000003342 alkenyl group Chemical group 0.000 claims description 12
125000000304 alkynyl group Chemical group 0.000 claims description 12
125000001589 carboacyl group Chemical group 0.000 claims description 12
239000002253 acid Substances 0.000 claims description 11
125000003545 alkoxy group Chemical group 0.000 claims description 10
229910052736 halogen Chemical group 0.000 claims description 10
150000002367 halogens Chemical group 0.000 claims description 10
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
239000011541 reaction mixture Substances 0.000 claims description 9
150000003839 salts Chemical class 0.000 claims description 9
238000005987 sulfurization reaction Methods 0.000 claims description 9
125000004423 acyloxy group Chemical group 0.000 claims description 8
125000004414 alkyl thio group Chemical group 0.000 claims description 8
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 8
125000004093 cyano group Chemical group *C#N 0.000 claims description 8
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 8
125000005236 alkanoylamino group Chemical group 0.000 claims description 7
125000004103 aminoalkyl group Chemical group 0.000 claims description 7
229910052740 iodine Inorganic materials 0.000 claims description 7
125000004953 trihalomethyl group Chemical group 0.000 claims description 7
230000002152 alkylating effect Effects 0.000 claims description 6
125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 6
125000001153 fluoro group Chemical group F* 0.000 claims description 6
229910000104 sodium hydride Inorganic materials 0.000 claims description 6
239000002904 solvent Substances 0.000 claims description 6
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical group [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 5
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 5
238000009835 boiling Methods 0.000 claims description 5
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
229910052794 bromium Inorganic materials 0.000 claims description 5
229910052799 carbon Inorganic materials 0.000 claims description 5
239000003153 chemical reaction reagent Substances 0.000 claims description 5
239000000460 chlorine Substances 0.000 claims description 5
229910052801 chlorine Inorganic materials 0.000 claims description 5
125000004966 cyanoalkyl group Chemical group 0.000 claims description 5
239000012312 sodium hydride Substances 0.000 claims description 5
125000001424 substituent group Chemical group 0.000 claims description 5
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
230000010933 acylation Effects 0.000 claims description 4
238000005917 acylation reaction Methods 0.000 claims description 4
150000001339 alkali metal compounds Chemical class 0.000 claims description 4
125000005092 alkenyloxycarbonyl group Chemical group 0.000 claims description 4
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 4
125000005079 alkoxycarbonylmethyl group Chemical group 0.000 claims description 4
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229910052731 fluorine Inorganic materials 0.000 claims description 4
239000011737 fluorine Substances 0.000 claims description 4
150000002431 hydrogen Chemical class 0.000 claims description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
239000003513 alkali Substances 0.000 claims description 3
150000001341 alkaline earth metal compounds Chemical class 0.000 claims description 3
150000007529 inorganic bases Chemical class 0.000 claims description 3
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 3
238000002955 isolation Methods 0.000 claims description 3
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
VRKMQYLHRKBKIO-UHFFFAOYSA-N 3-amino-6,7,9-trimethylpyrido[2,3-b][1,5]benzothiazepin-5-one Chemical compound O=C1N(C)C2=C(C)C=C(C)C=C2SC2=NC=C(N)C=C21 VRKMQYLHRKBKIO-UHFFFAOYSA-N 0.000 claims description 2
DGBVNIAUNCJNBL-UHFFFAOYSA-N 3-amino-6,7,9-trimethylpyrido[2,3-b][1,5]benzoxazepin-5-one Chemical compound O=C1N(C)C2=C(C)C=C(C)C=C2OC2=NC=C(N)C=C21 DGBVNIAUNCJNBL-UHFFFAOYSA-N 0.000 claims description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 2
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RLECCBFNWDXKPK-UHFFFAOYSA-N bis(trimethylsilyl)sulfide Chemical compound C[Si](C)(C)S[Si](C)(C)C RLECCBFNWDXKPK-UHFFFAOYSA-N 0.000 claims description 2
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125000000753 cycloalkyl group Chemical group 0.000 claims description 2
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239000011630 iodine Substances 0.000 claims description 2
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125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
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239000003960 organic solvent Substances 0.000 claims description 2
239000008194 pharmaceutical composition Substances 0.000 claims description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 claims description 2
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 claims description 2
229910000105 potassium hydride Inorganic materials 0.000 claims description 2
238000007363 ring formation reaction Methods 0.000 claims description 2
239000007858 starting material Substances 0.000 claims description 2
125000001544 thienyl group Chemical group 0.000 claims description 2
BDIWFCKBPZPBQT-UHFFFAOYSA-N tributyl(tributylstannylsulfanyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)S[Sn](CCCC)(CCCC)CCCC BDIWFCKBPZPBQT-UHFFFAOYSA-N 0.000 claims description 2
NBTHYJWPOYZDHL-UHFFFAOYSA-N tricyclohexyl(tricyclohexylstannylsulfanyl)stannane Chemical compound C1CCCCC1[Sn](C1CCCCC1)(C1CCCCC1)S[Sn](C1CCCCC1)(C1CCCCC1)C1CCCCC1 NBTHYJWPOYZDHL-UHFFFAOYSA-N 0.000 claims description 2
NTCQOKPUDSWFJF-UHFFFAOYSA-N triphenyl(triphenylstannylsulfanyl)stannane Chemical compound C=1C=CC=CC=1[Sn](C=1C=CC=CC=1)(C=1C=CC=CC=1)S[Sn](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 NTCQOKPUDSWFJF-UHFFFAOYSA-N 0.000 claims description 2
UYUIJOAWTJMMIV-UHFFFAOYSA-N 3-amino-6-ethyl-7,9-dimethylpyrido[2,3-b][1,5]benzoxazepin-5-one Chemical compound O=C1N(CC)C2=C(C)C=C(C)C=C2OC2=NC=C(N)C=C21 UYUIJOAWTJMMIV-UHFFFAOYSA-N 0.000 claims 2
IHRBNIIOMPLCAE-UHFFFAOYSA-N 3-amino-7,9-dimethyl-6-propylpyrido[2,3-b][1,5]benzothiazepin-5-one Chemical compound O=C1N(CCC)C2=C(C)C=C(C)C=C2SC2=NC=C(N)C=C21 IHRBNIIOMPLCAE-UHFFFAOYSA-N 0.000 claims 2
150000001721 carbon Chemical group 0.000 claims 2
CXDWIUWDGAESRK-UHFFFAOYSA-N 3-amino-6,9-dimethylpyrido[2,3-b][1,5]benzothiazepin-5-one Chemical compound O=C1N(C)C2=CC=C(C)C=C2SC2=NC=C(N)C=C21 CXDWIUWDGAESRK-UHFFFAOYSA-N 0.000 claims 1
MUKSMBAVCDPKRC-UHFFFAOYSA-N 3-amino-6,9-dimethylpyrido[2,3-b][1,5]benzoxazepin-5-one Chemical compound O=C1N(C)C2=CC=C(C)C=C2OC2=NC=C(N)C=C21 MUKSMBAVCDPKRC-UHFFFAOYSA-N 0.000 claims 1
VRGLMJBXFPGROI-UHFFFAOYSA-N 3-amino-7,9-dimethyl-6-propylpyrido[2,3-b][1,5]benzoxazepin-5-one Chemical compound O=C1N(CCC)C2=C(C)C=C(C)C=C2OC2=NC=C(N)C=C21 VRGLMJBXFPGROI-UHFFFAOYSA-N 0.000 claims 1
125000002252 acyl group Chemical group 0.000 claims 1
150000008052 alkyl sulfonates Chemical class 0.000 claims 1
125000005002 aryl methyl group Chemical group 0.000 claims 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

CA002024071A 1989-08-29 1990-08-27 Pyrido[2,3-b][1,5]benzoxazepine (et -thiazepine)-5(6h)-ones et -thiones et leur utilisation pour la prevention et le traitement des infections a hiv Expired - Fee Related CA2024071C (fr)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date
US40025389A	1989-08-29	1989-08-29
US400,253		1989-08-29
US53929490A	1990-06-15	1990-06-15
US539,294		1990-06-15

Publications (2)

Publication Number	Publication Date
CA2024071A1 CA2024071A1 (fr)	1991-03-01
CA2024071C true CA2024071C (fr)	2002-06-04

Family

ID=27016965

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002024071A Expired - Fee Related CA2024071C (fr)	1989-08-29	1990-08-27	Pyrido[2,3-b][1,5]benzoxazepine (et -thiazepine)-5(6h)-ones et -thiones et leur utilisation pour la prevention et le traitement des infections a hiv

Country Status (8)

Country	Link
AP (1)	AP190A (fr)
AU (1)	AU624264B2 (fr)
CA (1)	CA2024071C (fr)
FI (1)	FI93362C (fr)
HU (1)	HU206723B (fr)
NO (1)	NO177786C (fr)
OA (1)	OA09307A (fr)
PT (1)	PT95113B (fr)

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA802216A (en) *		1968-12-24	Hoffmann Charles	Heterocyclic compounds
CA554134A (fr) *		1958-03-11	Hoffmann Karl	Composes thia-aza-cycloheptadiene et procede pour leur fabrication
CA799979A (en) *		1968-11-26	Dr. Karl Thomae Gesellschaft Mit Beschrankter Haftung	5,6-dihydro-6-oxo-pyrido(2,3-b) (1,4)-benzoxazepines
GB1587128A (en) *	1977-04-07	1981-04-01	Hexachimie	Benzothiazepine derivatives
US4940704A (en) *	1989-08-16	1990-07-10	Hoechst-Roussel Pharmaceutical Inc.	Pyrido[3,4-b][1,4]benzoxazepines

1990
- 1990-08-27 CA CA002024071A patent/CA2024071C/fr not_active Expired - Fee Related
- 1990-08-28 HU HU905510A patent/HU206723B/hu not_active IP Right Cessation
- 1990-08-28 PT PT95113A patent/PT95113B/pt unknown
- 1990-08-28 FI FI904244A patent/FI93362C/fi not_active IP Right Cessation
- 1990-08-28 NO NO903778A patent/NO177786C/no unknown
- 1990-08-29 OA OA59847A patent/OA09307A/xx unknown
- 1990-08-29 AU AU61917/90A patent/AU624264B2/en not_active Ceased
- 1990-08-29 AP APAP/P/1990/000203A patent/AP190A/en active

Also Published As

Publication number	Publication date
FI93362C (fi)	1995-03-27
AP9000203A0 (en)	1990-10-31
HU905510D0 (en)	1991-02-28
OA09307A (en)	1992-09-15
PT95113B (pt)	1997-04-30
NO903778D0 (no)	1990-08-28
AP190A (en)	1992-05-04
NO177786B (no)	1995-08-14
NO903778L (no)	1991-03-01
FI93362B (fi)	1994-12-15
CA2024071A1 (fr)	1991-03-01
AU624264B2 (en)	1992-06-04
HUT57777A (en)	1991-12-30
HU206723B (en)	1992-12-28
FI904244A0 (fi)	1990-08-28
NO177786C (no)	1995-11-22
PT95113A (pt)	1991-05-22
AU6191790A (en)	1991-03-07

Legal Events

Date	Code	Title	Description
1997-04-15	EEER	Examination request
2004-08-27	MKLA	Lapsed

Publication	Publication Date	Title
US5571809A (en)	1996-11-05	The treatment of HIV-1 infection using certain pyridodiazepines
EP0429987B1 (fr)	1999-03-17	5,11-Dihydro-6H-dipyrido[3,2-b:2'3'-e] [1,4]diazépines et leur utilisation pour prévenir ou traiter l'infection par le VIH
CA2019812C (fr)	2000-11-21	Nouveau 5,11-dihydro-6h-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-ones et leur utilisation dans la prevention et le traitement du sida
EP0393604B1 (fr)	1997-12-29	6,11-Dihydro-5H-pyrido(2,3-b)(1,5)benzodiazépine-5-ones et thiones et leur utilisation pour la prévention ou le traitement du SIDA
US5087625A (en)	1992-02-11	Pyridodiazepines and their use in the prevention or treatment of HIV infection
EP0419861B1 (fr)	1995-11-02	Utilisation de dibenzo[b,f][1,4]oxazépine (et thiazépine)-11(10H)-ones et -thiones pour l'obtention d'un médicament destiné à la prévention ou le traitement du SIDA
EP0745083B1 (fr)	1998-05-20	2-HETEROARYL-5,11-DIHYDRO-6H-DIPYRIDO[3,2-b:2',3'-e][1,4] DIAZEPINES ET LEUR UTILISATION DANS LA PREVENTION OU LE TRAITEMENT DE L'INFECTION A VIH
CA2024071C (fr)	2002-06-04	Pyrido[2,3-b][1,5]benzoxazepine (et -thiazepine)-5(6h)-ones et -thiones et leur utilisation pour la prevention et le traitement des infections a hiv
EP0415303B1 (fr)	1995-12-13	Pyrido [2,3-b][1,5]benzoxazépine (et thiazépine)-5(6H)-ones et thiones et leur utilisation pour la prévention et le traitement de l'infection par le HIV
US5550122A (en)	1996-08-27	Pyrido[2,3-b][1,5]benzoxazepin (and thiazepin)-5(6H)-ones and thiones and their use on the treatment of HIV infection
US5547951A (en)	1996-08-20	Pyrido[2,3-b][1,4]benzoxazepin (and thiazepin)-6(5H)-ones and -thiones and their use in the prevention or treatment of HIV-1 infection
EP0393530B1 (fr)	1994-12-28	5,11-Dihydro-6H-pyrido(2,3-b)(1,4)benzodiazépine-6-ones et thiones et leur utilisation pour la prévention et le traitement du SIDA
US5837704A (en)	1998-11-17	2-heteroaryl-5,11-dihydro-6H-dipyrido 3,2-B:2',3'-E! 1,4!diazepines and their use in the prevention or treatment of HIV infection
US5602113A (en)	1997-02-11	Pyridobenzo- and pyridiothieno-diazepines useful for the treatment of HIV infection
EP0415304A2 (fr)	1991-03-06	Dipyrido[3,2-b:2',3'-e][1,4]oxazépine, (et thiazépine)-6(5H)-ones et leur utilisation pour la prévention ou le traitement du SIDA
US5550117A (en)	1996-08-27	Dipyrido[3,2-B:2 ',3'-E][1,4]Diaqzepines and their use in the treatment of HIV infection
HK1011025B (en)	2000-04-20	5,11-dihydro-6h-dipyrido[3,2-b:2',3'-e][1,4]diazepines and their use in the preventionor treatment of hiv infection