CA1338445C - 1,2,4-benzotriazine oxides as radiosensitizers and selective cytotoxic agents - Google Patents
1,2,4-benzotriazine oxides as radiosensitizers and selective cytotoxic agentsInfo
- Publication number
- CA1338445C CA1338445C CA000540932A CA540932A CA1338445C CA 1338445 C CA1338445 C CA 1338445C CA 000540932 A CA000540932 A CA 000540932A CA 540932 A CA540932 A CA 540932A CA 1338445 C CA1338445 C CA 1338445C
- Authority
- CA
- Canada
- Prior art keywords
- amino
- hydrocarbyl
- hydroxy
- independently
- 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.)
- Expired - Fee Related
Links
- 231100000599 cytotoxic agent Toxicity 0.000 title abstract description 12
- 239000002254 cytotoxic agent Substances 0.000 title abstract description 11
- 229940127089 cytotoxic agent Drugs 0.000 title abstract description 11
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- 150000001875 compounds Chemical class 0.000 claims abstract description 66
- 125000001183 hydrocarbyl group Chemical group 0.000 claims abstract description 36
- 206010021143 Hypoxia Diseases 0.000 claims abstract description 35
- 230000001146 hypoxic effect Effects 0.000 claims abstract description 30
- 210000004881 tumor cell Anatomy 0.000 claims abstract description 23
- -1 amino, morpholino Chemical group 0.000 claims abstract description 22
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 20
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 19
- 150000002367 halogens Chemical class 0.000 claims abstract description 14
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 12
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims abstract description 10
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims abstract description 10
- 125000004423 acyloxy group Chemical group 0.000 claims abstract description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 9
- 239000004593 Epoxy Chemical group 0.000 claims abstract description 8
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 8
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 8
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 8
- 125000001424 substituent group Chemical group 0.000 claims abstract description 8
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 7
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- 230000022534 cell killing Effects 0.000 description 6
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
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- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 4
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 4
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
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- 238000007792 addition Methods 0.000 description 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 4
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- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- GDAXJBDYNVDMDF-UHFFFAOYSA-N 1,2,4-benzotriazine Chemical compound N1=NC=NC2=CC=CC=C21 GDAXJBDYNVDMDF-UHFFFAOYSA-N 0.000 description 3
- LXKCBUZYEAQGKP-UHFFFAOYSA-N 4-decyl-2-nitroaniline Chemical compound CCCCCCCCCCC1=CC=C(N)C([N+]([O-])=O)=C1 LXKCBUZYEAQGKP-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
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- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
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- 201000009030 Carcinoma Diseases 0.000 description 3
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D253/00—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00
- C07D253/08—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00 condensed with carbocyclic rings or ring systems
- C07D253/10—Condensed 1,2,4-triazines; Hydrogenated condensed 1,2,4-triazines
-
- 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
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- 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
- A61K31/535—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 oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0038—Radiosensitizing, i.e. administration of pharmaceutical agents that enhance the effect of radiotherapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US91190686A | 1986-09-25 | 1986-09-25 | |
| US911,906 | 1986-09-25 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1338445C true CA1338445C (en) | 1996-07-09 |
Family
ID=25431084
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000540932A Expired - Fee Related CA1338445C (en) | 1986-09-25 | 1987-06-30 | 1,2,4-benzotriazine oxides as radiosensitizers and selective cytotoxic agents |
Country Status (5)
| Country | Link |
|---|---|
| JP (1) | JP2668232B2 (enrdf_load_stackoverflow) |
| CA (1) | CA1338445C (enrdf_load_stackoverflow) |
| DE (2) | DE3790581T1 (enrdf_load_stackoverflow) |
| GB (1) | GB2203151B (enrdf_load_stackoverflow) |
| WO (1) | WO1988002366A1 (enrdf_load_stackoverflow) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5175287A (en) * | 1986-09-25 | 1992-12-29 | S R I International | Process for preparing 1,2,4-benzotriazine oxides |
| US5624925A (en) | 1986-09-25 | 1997-04-29 | Sri International | 1,2,4-benzotriazine oxides as radiosensitizers and selective cytotoxic agents |
| IE62911B1 (en) * | 1988-03-18 | 1995-03-08 | Stanford Res Inst Int | 1,2,4-benzotriazine oxides as radiosensitizers and selective cytotoxic agents |
| GR1000941B (el) * | 1989-03-17 | 1993-03-16 | Stanford Res Inst Int | Μεθοδος παρασκευης οξειδιων 1,2,4,βενζοτριαζινης. |
| DE68929050T2 (de) * | 1989-09-18 | 2000-02-03 | Sri International, Menlo Park | 1,2,4-benzotriazinoxide als funkempfindliche und selektive zytotoxische mittel |
| US5672702A (en) * | 1995-12-04 | 1997-09-30 | Sanofi | Process for preparing 3 amino 1, 2, 4-benzotriazine dioxide |
| EP2800744A4 (en) * | 2011-12-07 | 2015-06-03 | Sri Internat Inc | BENZOTRIAZINE OXIDE AS A MEDICAMENT AGAINST MYCOBACTERIUM TUBERCULOSIS |
| US10981953B2 (en) | 2013-12-26 | 2021-04-20 | Toagosei Co, Ltd. | Method for promoting expression of calreticulin, and synthetic peptide for use in method for promoting expression of calreticulin |
| JP6872713B2 (ja) | 2015-05-29 | 2021-05-19 | 東亞合成株式会社 | 腫瘍細胞の放射線感受性を増大させる合成ペプチド及びその利用 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2489352A (en) * | 1946-04-10 | 1949-11-29 | Merck & Co Inc | Halogen compounds of 3 aminobenzotriazine 1, 2, 4 oxide-1 |
| US2489359A (en) * | 1947-01-10 | 1949-11-29 | Merck & Co Inc | Benzotriazines |
| CH487171A (de) * | 1963-10-22 | 1970-03-15 | Siegfried Ag | Verfahren zur Herstellung therapeutisch wirksamer 1,2-Dihydro-1,2,4-benztriazine |
| DE1809390A1 (de) * | 1968-11-16 | 1970-06-11 | Bayer Ag | Phosphor-,Phosphon- bzw.Thionophosphor-(-phosphon)-saeureester und Verfahren zu ihrer Herstellung |
| IL44058A (en) * | 1973-02-02 | 1978-10-31 | Ciba Geigy Ag | 3amino-1,2,4-benzotriazine 1,4-di-noxide derivatives, their preparation and compositions for the control of microorganisms containing them |
| DE2538179C2 (de) * | 1975-08-27 | 1986-05-28 | Bayer Ag, 5090 Leverkusen | 3-Alkoxy-benzo-1,2,4-triazine, Verfahren zu ihrer Herstellung sowie ihre Verwendung als Fungizide |
| DE2740887A1 (de) * | 1977-09-10 | 1979-03-22 | Bayer Ag | Mittel zur bekaempfung von pflanzenbakteriosen |
-
1987
- 1987-06-16 DE DE19873790581 patent/DE3790581T1/de active Pending
- 1987-06-16 JP JP62504083A patent/JP2668232B2/ja not_active Expired - Lifetime
- 1987-06-16 DE DE3790581A patent/DE3790581B4/de not_active Expired - Lifetime
- 1987-06-16 GB GB8810634A patent/GB2203151B/en not_active Expired - Lifetime
- 1987-06-16 WO PCT/US1987/001412 patent/WO1988002366A1/en active Application Filing
- 1987-06-30 CA CA000540932A patent/CA1338445C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| WO1988002366A1 (en) | 1988-04-07 |
| GB8810634D0 (en) | 1988-07-06 |
| GB2203151B (en) | 1991-05-29 |
| DE3790581B4 (de) | 2004-12-23 |
| DE3790581T1 (enrdf_load_stackoverflow) | 1988-08-25 |
| GB2203151A (en) | 1988-10-12 |
| JPH01500826A (ja) | 1989-03-23 |
| JP2668232B2 (ja) | 1997-10-27 |
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| Date | Code | Title | Description |
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| MKLA | Lapsed |