CN1127115A - 3,8-二氧代-5-硫代-1,4-二氮杂二环[4.2.0]辛烷化合物在抗肿瘤治疗中的应用 - Google Patents
3,8-二氧代-5-硫代-1,4-二氮杂二环[4.2.0]辛烷化合物在抗肿瘤治疗中的应用 Download PDFInfo
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- CN1127115A CN1127115A CN95116888A CN95116888A CN1127115A CN 1127115 A CN1127115 A CN 1127115A CN 95116888 A CN95116888 A CN 95116888A CN 95116888 A CN95116888 A CN 95116888A CN 1127115 A CN1127115 A CN 1127115A
- Authority
- CN
- China
- Prior art keywords
- hydrogen
- octane
- thia
- diazabicyclo
- halogen
- Prior art date
- 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.)
- Pending
Links
- 150000001875 compounds Chemical class 0.000 title abstract description 10
- 238000002560 therapeutic procedure Methods 0.000 title description 2
- 230000000259 anti-tumor effect Effects 0.000 title 1
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 9
- 239000001257 hydrogen Substances 0.000 claims abstract description 9
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 6
- 150000002367 halogens Chemical class 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 3
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000005544 phthalimido group Chemical group 0.000 claims abstract description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 3
- 239000004615 ingredient Substances 0.000 claims description 3
- -1 octane compound Chemical group 0.000 claims description 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- 150000003217 pyrazoles Chemical class 0.000 claims description 2
- 230000001629 suppression Effects 0.000 abstract description 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 abstract 1
- 208000019065 cervical carcinoma Diseases 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- 206010008342 Cervix carcinoma Diseases 0.000 description 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 2
- 201000010881 cervical cancer Diseases 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000008246 gaseous mixture Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical class CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000003952 β-lactams Chemical group 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/549—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame having two or more nitrogen atoms in the same ring, e.g. hydrochlorothiazide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
本发明涉及具有通式I的3,8-二氧代-5-硫代-1,4-二氮杂二环[4.2.0]辛烷(其中的基团具有下列含义:R1为氢、卤素,R2为氢、卤素、氨基、PhCH2CONH、PhOCH2CONH、苯二甲酰亚氨基、邻-甲基NHCOC6H4CONH、3-邻-氯苯基-5-甲基-异噁唑基-4-羰基氨基,R3为氢、烷基、苄基、杂环如异噁唑、吡唑,n是1或2)。在应用实施例中公开了用各种取代的3,8-二氧代-5-硫代-1,4-二氮杂二环[4.2.0]辛烷衍生物抑制子宫颈癌细胞(Hela)的作用。
Description
R1 为氢、卤素,
R2 为氢、卤素、氨基、PhCH2CONH、PhOCH2CONH、
苯二甲酰亚氨基、邻-甲基NHCOC6H4CONH、
3-邻-氯苯基-5-甲基-异噁唑基-4-羰基氨基,
R3 为氢、烷基、苄基、杂环如异噁唑、吡唑,
n是1或2,及其在抗菌治疗中作为药物有效成分的有效性。
本发明也涉及具有通式I的化合物,以及,特别是,其以规定量加入能有效抑制肿瘤细胞的药物制剂中作为有效成分的用途。
根据我们对现有技术的了解,还未知在抗肿瘤治疗中使用过具有类似结构或任何其它β-内酰胺结构的化合物。
我们发现具有通式I的3,8-二氧代-5-硫代-1,4-二氮杂二环〔4.2.0〕辛烷类似物(其中的基团具有上述含义)可以很强地抑制子宫颈癌细胞(HeLa)的生长。通过使用浓度为10-3-10-6M的式I化合物,72小时后对肿瘤细胞的抑制效果达到25%-65%。在浓度为5×10-4M时获得了最好的效果。
下列实施例是关于具有通式I的化合物对子宫颈癌的抑制效果,表明了该化合物还能有效地抑制其它肿瘤细胞的可能性。检测方法
将细胞于DMEM(Dulbecco改进的Eagle培养基)生长培养基中〔其中补充了胎牛血清(FCS)(10%)、谷氨酰胺(2mM)、青霉素(100U/ml)、链霉素(100μg/ml)和Hepes(1mM)〕在pH7、温度为37℃以及在含有空气和5%CO2的混合气流通的条件下培养12小时之内。将104细胞/ml浓度的细胞于24或96孔细胞培养平板上增殖。12小时后,加入浓度为10-3-10-6M的式I化合物溶液。先将所有物质在二甲基甲酰胺中制备成10-M的溶液,再用细胞生长培养基稀释成所需浓度。加入活性物质72小时后用电子计数器进行细胞计数,测定化合物I的抑制效果,如下列实施例中所示:
1×10-4M 25%
Claims (1)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
HRP940577A | 1994-09-21 | ||
HR940577A HRP940577B1 (en) | 1994-09-21 | 1994-09-21 | Use of 5-thia-1,4-diazabicyclo (4.2.0) octane-3,8-dioxo compounds in antitumor therapy |
Publications (1)
Publication Number | Publication Date |
---|---|
CN1127115A true CN1127115A (zh) | 1996-07-24 |
Family
ID=10946157
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN95116888A Pending CN1127115A (zh) | 1994-09-21 | 1995-09-21 | 3,8-二氧代-5-硫代-1,4-二氮杂二环[4.2.0]辛烷化合物在抗肿瘤治疗中的应用 |
Country Status (14)
Country | Link |
---|---|
EP (1) | EP0705606B1 (zh) |
JP (1) | JPH08310954A (zh) |
CN (1) | CN1127115A (zh) |
AT (1) | ATE164069T1 (zh) |
BG (1) | BG62237B1 (zh) |
CA (1) | CA2158678C (zh) |
CZ (1) | CZ285621B6 (zh) |
DE (1) | DE69501810T2 (zh) |
ES (1) | ES2115303T3 (zh) |
HR (1) | HRP940577B1 (zh) |
HU (1) | HU218287B (zh) |
RU (1) | RU2136284C1 (zh) |
SI (1) | SI9500297A (zh) |
SK (1) | SK280815B6 (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011035518A1 (zh) * | 2009-09-23 | 2011-03-31 | 辽宁利锋科技开发有限公司 | 嘧啶衍生物和类似物及其制备方法和用途 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5598188A (en) * | 1979-01-23 | 1980-07-25 | Mitsui Toatsu Chem Inc | Novel cephalosporin and its preparation |
JPS57171994A (en) * | 1981-04-15 | 1982-10-22 | Asahi Chem Ind Co Ltd | Novel compound |
HRP921292A2 (en) | 1992-11-17 | 1994-08-31 | Pliva Pharm & Chem Works | 5-thia-1,4-diazabicyclo (4.2.0.)octane -3,8-dioxo analogs of beta-lactams, the process for the preparation and use thereof |
-
1994
- 1994-09-21 HR HR940577A patent/HRP940577B1/xx not_active IP Right Cessation
-
1995
- 1995-09-18 DE DE69501810T patent/DE69501810T2/de not_active Expired - Fee Related
- 1995-09-18 AT AT95114673T patent/ATE164069T1/de not_active IP Right Cessation
- 1995-09-18 ES ES95114673T patent/ES2115303T3/es not_active Expired - Lifetime
- 1995-09-18 EP EP95114673A patent/EP0705606B1/en not_active Expired - Lifetime
- 1995-09-20 CZ CZ952447A patent/CZ285621B6/cs not_active IP Right Cessation
- 1995-09-20 JP JP7241717A patent/JPH08310954A/ja active Pending
- 1995-09-20 RU RU95116239A patent/RU2136284C1/ru active
- 1995-09-20 CA CA002158678A patent/CA2158678C/en not_active Expired - Fee Related
- 1995-09-21 SK SK1170-95A patent/SK280815B6/sk unknown
- 1995-09-21 CN CN95116888A patent/CN1127115A/zh active Pending
- 1995-09-21 HU HU9502770A patent/HU218287B/hu not_active IP Right Cessation
- 1995-09-21 SI SI9500297A patent/SI9500297A/sl unknown
- 1995-09-21 BG BG100020A patent/BG62237B1/bg unknown
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011035518A1 (zh) * | 2009-09-23 | 2011-03-31 | 辽宁利锋科技开发有限公司 | 嘧啶衍生物和类似物及其制备方法和用途 |
Also Published As
Publication number | Publication date |
---|---|
SK117095A3 (en) | 1996-09-04 |
EP0705606B1 (en) | 1998-03-18 |
SK280815B6 (sk) | 2000-08-14 |
CA2158678A1 (en) | 1996-03-22 |
CZ285621B6 (cs) | 1999-10-13 |
CZ244795A3 (en) | 1996-04-17 |
HU9502770D0 (en) | 1995-11-28 |
DE69501810T2 (de) | 1998-09-24 |
ATE164069T1 (de) | 1998-04-15 |
BG100020A (bg) | 1996-04-30 |
BG62237B1 (bg) | 1999-06-30 |
ES2115303T3 (es) | 1998-06-16 |
HRP940577A2 (en) | 1997-04-30 |
HUT74422A (en) | 1996-12-30 |
RU2136284C1 (ru) | 1999-09-10 |
HU218287B (en) | 2000-07-28 |
DE69501810D1 (de) | 1998-04-23 |
EP0705606A1 (en) | 1996-04-10 |
SI9500297A (en) | 1996-04-30 |
CA2158678C (en) | 2000-04-18 |
HRP940577B1 (en) | 1998-12-31 |
JPH08310954A (ja) | 1996-11-26 |
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SE01 | Entry into force of request for substantive examination | ||
C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
WD01 | Invention patent application deemed withdrawn after publication |