CH634845A5 - Pharmaceutically useful pyrimido(1,2-a)benzimidazole derivatives and corresponding preparations. - Google Patents

Pharmaceutically useful pyrimido(1,2-a)benzimidazole derivatives and corresponding preparations. Download PDF

Info

Publication number: CH634845A5
Authority: CH; Switzerland
Prior art keywords: hydrogen; carbon atoms; benzoyl; radicals; methyl
Prior art date: 1977-08-09

Application number

CH263582A

Other languages

German (de)

English (en)

Inventor

Stuart Dennett Mills

Original Assignee

Ici 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.)

1977-08-09

Filing date

1978-01-01

Publication date

1983-02-28

1978-01-01 Application filed by Ici Ltd filed Critical Ici Ltd

1983-02-28 Publication of CH634845A5 publication Critical patent/CH634845A5/de

Links

HOHWYQSDLRTVDK-UHFFFAOYSA-N pyrimido[1,2-a]benzimidazole Chemical class N1=CC=CN2C3=CC=CC=C3N=C21 HOHWYQSDLRTVDK-UHFFFAOYSA-N 0.000 title claims description 6
238000002360 preparation method Methods 0.000 title abstract description 14
210000001772 blood platelet Anatomy 0.000 claims abstract description 18
230000004520 agglutination Effects 0.000 claims abstract description 12
-1 methoxy, ethoxy, isopropoxy, acetyl Chemical group 0.000 claims description 90
125000004432 carbon atom Chemical group C* 0.000 claims description 78
229910052739 hydrogen Inorganic materials 0.000 claims description 73
239000001257 hydrogen Substances 0.000 claims description 73
150000001875 compounds Chemical class 0.000 claims description 71
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 57
125000005843 halogen group Chemical group 0.000 claims description 15
150000002431 hydrogen Chemical class 0.000 claims description 15
125000004093 cyano group Chemical group *C#N 0.000 claims description 13
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
239000003085 diluting agent Substances 0.000 claims description 8
125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims description 7
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
125000002252 acyl group Chemical group 0.000 claims description 6
239000000460 chlorine Substances 0.000 claims description 6
RJIXIIOSXWJCPX-UHFFFAOYSA-N 8-benzoyl-4-methyl-4,10-dihydro-3h-pyrimido[1,2-a]benzimidazol-2-one Chemical compound C=1C=C2N3C(C)CC(=O)NC3=NC2=CC=1C(=O)C1=CC=CC=C1 RJIXIIOSXWJCPX-UHFFFAOYSA-N 0.000 claims description 5
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
125000004414 alkyl thio group Chemical group 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
125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
229910052801 chlorine Inorganic materials 0.000 claims description 5
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
229940058303 antinematodal benzimidazole derivative Drugs 0.000 claims description 4
239000011737 fluorine Substances 0.000 claims description 4
229910052731 fluorine Inorganic materials 0.000 claims description 4
FFZKHULPLWYDQD-UHFFFAOYSA-N 12,14-dioxa-2,6,8-triazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(16),7,9,11(15)-tetraen-5-one Chemical compound C1=C2N3CCC(=O)NC3=NC2=CC2=C1OCO2 FFZKHULPLWYDQD-UHFFFAOYSA-N 0.000 claims description 3
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 3
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 3
239000000825 pharmaceutical preparation Substances 0.000 claims description 3
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 3
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
230000001882 diuretic effect Effects 0.000 claims description 2
230000001747 exhibiting effect Effects 0.000 claims description 2
238000011282 treatment Methods 0.000 abstract description 4
208000007536 Thrombosis Diseases 0.000 abstract description 3
238000011321 prophylaxis Methods 0.000 abstract description 3
208000021331 vascular occlusion disease Diseases 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 72
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 69
239000000203 mixture Substances 0.000 description 59
239000000243 solution Substances 0.000 description 36
BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 35
229910052799 carbon Inorganic materials 0.000 description 35
238000002844 melting Methods 0.000 description 35
230000008018 melting Effects 0.000 description 35
150000001721 carbon Chemical group 0.000 description 34
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
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239000007787 solid Substances 0.000 description 26
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238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 18
239000007858 starting material Substances 0.000 description 18
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238000000034 method Methods 0.000 description 17
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238000012360 testing method Methods 0.000 description 9
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
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239000002585 base Substances 0.000 description 7
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XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 6
GJYVNFASHFTWEU-UHFFFAOYSA-N 8-acetyl-4,10-dihydro-3h-pyrimido[1,2-a]benzimidazol-2-one Chemical compound C1CC(=O)NC2=NC3=CC(C(=O)C)=CC=C3N21 GJYVNFASHFTWEU-UHFFFAOYSA-N 0.000 description 6
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 6
210000004369 blood Anatomy 0.000 description 6
239000008280 blood Substances 0.000 description 6
238000001727 in vivo Methods 0.000 description 6
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125000001424 substituent group Chemical group 0.000 description 6
206010043554 thrombocytopenia Diseases 0.000 description 6
XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 5
JWYUFVNJZUSCSM-UHFFFAOYSA-N 2-aminobenzimidazole Chemical compound C1=CC=C2NC(N)=NC2=C1 JWYUFVNJZUSCSM-UHFFFAOYSA-N 0.000 description 5
230000000694 effects Effects 0.000 description 5
239000000463 material Substances 0.000 description 5
MELMCGUWWNPXAX-UHFFFAOYSA-N 7-chloro-8-methyl-4,10-dihydro-3h-pyrimido[1,2-a]benzimidazol-2-one Chemical compound N1=C2NC(=O)CCN2C2=C1C=C(C)C(Cl)=C2 MELMCGUWWNPXAX-UHFFFAOYSA-N 0.000 description 4
102000008186 Collagen Human genes 0.000 description 4
108010035532 Collagen Proteins 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
241000699670 Mus sp. Species 0.000 description 4
125000003118 aryl group Chemical group 0.000 description 4
229920001436 collagen Polymers 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
ASVPUUDJBLBNEH-UHFFFAOYSA-N 1-(2-amino-3h-benzimidazol-5-yl)ethanone Chemical compound CC(=O)C1=CC=C2N=C(N)NC2=C1 ASVPUUDJBLBNEH-UHFFFAOYSA-N 0.000 description 3
HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 3
JCRWHUMNIOSWNT-UHFFFAOYSA-N 2-oxo-4,10-dihydro-3h-pyrimido[1,2-a]benzimidazole-8-carbonitrile Chemical compound N#CC1=CC=C2N3CCC(=O)NC3=NC2=C1 JCRWHUMNIOSWNT-UHFFFAOYSA-N 0.000 description 3
KKPITQHNEPXHKV-UHFFFAOYSA-N 3-(5-acetyl-2-aminobenzimidazol-1-yl)propanenitrile Chemical compound CC(=O)C1=CC=C2N(CCC#N)C(N)=NC2=C1 KKPITQHNEPXHKV-UHFFFAOYSA-N 0.000 description 3
IFODSVOKJRKVAH-UHFFFAOYSA-N 5,6-di(propan-2-yloxy)-1h-benzimidazol-2-amine Chemical compound C1=C(OC(C)C)C(OC(C)C)=CC2=C1NC(N)=N2 IFODSVOKJRKVAH-UHFFFAOYSA-N 0.000 description 3
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DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
238000005481 NMR spectroscopy Methods 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
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125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
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ZSAWWJYNDFERFN-UHFFFAOYSA-N 4,7-dimethyl-1h-benzimidazol-2-amine Chemical compound CC1=CC=C(C)C2=C1N=C(N)N2 ZSAWWJYNDFERFN-UHFFFAOYSA-N 0.000 description 2
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238000005658 halogenation reaction Methods 0.000 description 1
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LNDNYPUTPRJGSQ-UHFFFAOYSA-N methyl 3-(2-amino-5-benzoylbenzimidazol-1-yl)propanoate Chemical compound C=1C=C2N(CCC(=O)OC)C(N)=NC2=CC=1C(=O)C1=CC=CC=C1 LNDNYPUTPRJGSQ-UHFFFAOYSA-N 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
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229940016286 microcrystalline cellulose Drugs 0.000 description 1
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235000010755 mineral Nutrition 0.000 description 1
238000002156 mixing Methods 0.000 description 1
YWANGSCDWBUSBK-UHFFFAOYSA-N n-(5-chloro-2-nitrophenyl)acetamide Chemical compound CC(=O)NC1=CC(Cl)=CC=C1[N+]([O-])=O YWANGSCDWBUSBK-UHFFFAOYSA-N 0.000 description 1
ALBBQFWHUCTZFM-UHFFFAOYSA-N n-methyl-1h-benzimidazol-2-amine Chemical compound C1=CC=C2NC(NC)=NC2=C1 ALBBQFWHUCTZFM-UHFFFAOYSA-N 0.000 description 1
238000006396 nitration reaction Methods 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
238000010899 nucleation Methods 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
239000002245 particle Substances 0.000 description 1
150000004965 peroxy acids Chemical class 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
239000012071 phase Substances 0.000 description 1
UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
210000004623 platelet-rich plasma Anatomy 0.000 description 1
229920000137 polyphosphoric acid Polymers 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000000047 product Substances 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
238000000746 purification Methods 0.000 description 1
125000001453 quaternary ammonium group Chemical group 0.000 description 1
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 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000002390 rotary evaporation Methods 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
239000012265 solid product Substances 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
238000003860 storage Methods 0.000 description 1
MBGGBVCUIVRRBF-UHFFFAOYSA-N sulfinpyrazone Chemical compound O=C1N(C=2C=CC=CC=2)N(C=2C=CC=CC=2)C(=O)C1CCS(=O)C1=CC=CC=C1 MBGGBVCUIVRRBF-UHFFFAOYSA-N 0.000 description 1
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230000001225 therapeutic effect Effects 0.000 description 1
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229960005001 ticlopidine Drugs 0.000 description 1
ZFDIRQKJPRINOQ-UHFFFAOYSA-N transbutenic acid ethyl ester Natural products CCOC(=O)C=CC ZFDIRQKJPRINOQ-UHFFFAOYSA-N 0.000 description 1
238000002054 transplantation Methods 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D235/30—Nitrogen atoms not forming part of a nitro radical
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/14—Ortho-condensed systems

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

CH263582A 1977-08-09 1978-01-01 Pharmaceutically useful pyrimido(1,2-a)benzimidazole derivatives and corresponding preparations. CH634845A5 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GB3334177		1977-08-09

Publications (1)

Publication Number	Publication Date
CH634845A5 true CH634845A5 (en)	1983-02-28

Family

ID=10351713

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CH263582A CH634845A5 (en)	1977-08-09	1978-01-01	Pharmaceutically useful pyrimido(1,2-a)benzimidazole derivatives and corresponding preparations.

Country Status (6)

Country	Link
AR (1)	AR217274A1 (da)
CH (1)	CH634845A5 (da)
DK (1)	DK23578A (da)
ES (1)	ES473400A1 (da)
PL (1)	PL106798B1 (da)
SU (1)	SU805947A3 (da)

1977
- 1977-12-08 PL PL21020977A patent/PL106798B1/pl unknown
1978
- 1978-01-01 CH CH263582A patent/CH634845A5/de not_active IP Right Cessation
- 1978-01-13 AR AR27071078A patent/AR217274A1/es active
- 1978-01-17 DK DK23578A patent/DK23578A/da not_active Application Discontinuation
- 1978-09-15 ES ES473400A patent/ES473400A1/es not_active Expired
- 1978-10-06 SU SU782673453A patent/SU805947A3/ru active

Also Published As

Publication number	Publication date
DK23578A (da)	1979-02-10
PL106798B1 (pl)	1980-01-31
SU805947A3 (ru)	1981-02-15
AR217274A1 (es)	1980-03-14
ES473400A1 (es)	1979-04-16

Legal Events

Date	Code	Title	Description
1985-09-30	PL	Patent ceased
2024-10-31	PL	Patent ceased

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