GB885078A - 3:4-dihydro-1:2:4-benzothiadiazine-1:1-dioxides and process for their manufacture - Google Patents
3:4-dihydro-1:2:4-benzothiadiazine-1:1-dioxides and process for their manufactureInfo
- Publication number
- GB885078A GB885078A GB1139/60A GB113960A GB885078A GB 885078 A GB885078 A GB 885078A GB 1139/60 A GB1139/60 A GB 1139/60A GB 113960 A GB113960 A GB 113960A GB 885078 A GB885078 A GB 885078A
- Authority
- GB
- United Kingdom
- Prior art keywords
- chloro
- nitrobenzene
- methylsulphamoyl
- aniline
- sulphamoyl
- 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
Links
- 238000004519 manufacturing process Methods 0.000 title 1
- 238000000034 method Methods 0.000 title 1
- -1 dimethyl sulphate or Chemical compound 0.000 abstract 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 abstract 3
- 150000001299 aldehydes Chemical class 0.000 abstract 3
- 150000003839 salts Chemical class 0.000 abstract 3
- OKXYPUDKVYVJDI-UHFFFAOYSA-N 3,4-dihydro-2h-1$l^{6},2,4-benzothiadiazine 1,1-dioxide Chemical class C1=CC=C2S(=O)(=O)NCNC2=C1 OKXYPUDKVYVJDI-UHFFFAOYSA-N 0.000 abstract 2
- YGHRJJRRZDOVPD-UHFFFAOYSA-N 3-methylbutanal Chemical compound CC(C)CC=O YGHRJJRRZDOVPD-UHFFFAOYSA-N 0.000 abstract 2
- HZLMCYKKQJTLER-UHFFFAOYSA-N 4-amino-6-chloro-3-n-methylbenzene-1,3-disulfonamide Chemical compound CNS(=O)(=O)C1=CC(S(N)(=O)=O)=C(Cl)C=C1N HZLMCYKKQJTLER-UHFFFAOYSA-N 0.000 abstract 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 abstract 2
- RPTUSVTUFVMDQK-UHFFFAOYSA-N Hidralazin Chemical compound C1=CC=C2C(NN)=NN=CC2=C1 RPTUSVTUFVMDQK-UHFFFAOYSA-N 0.000 abstract 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 abstract 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 abstract 2
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 abstract 2
- 150000004820 halides Chemical class 0.000 abstract 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 abstract 2
- 238000002360 preparation method Methods 0.000 abstract 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 abstract 2
- OVXJWSYBABKZMD-UHFFFAOYSA-N 2-chloro-1,1-diethoxyethane Chemical compound CCOC(CCl)OCC OVXJWSYBABKZMD-UHFFFAOYSA-N 0.000 abstract 1
- IXLAUVLEFWYDPD-UHFFFAOYSA-N 3,4-dihydro-2h-1,2,3-benzothiadiazine Chemical compound C1=CC=C2CNNSC2=C1 IXLAUVLEFWYDPD-UHFFFAOYSA-N 0.000 abstract 1
- PNPCRKVUWYDDST-UHFFFAOYSA-N 3-chloroaniline Chemical compound NC1=CC=CC(Cl)=C1 PNPCRKVUWYDDST-UHFFFAOYSA-N 0.000 abstract 1
- OETUDWYVNUKHJY-UHFFFAOYSA-N 4-amino-6-chloro-1-n,3-n-dimethylbenzene-1,3-disulfonamide Chemical compound CNS(=O)(=O)C1=CC(S(=O)(=O)NC)=C(Cl)C=C1N OETUDWYVNUKHJY-UHFFFAOYSA-N 0.000 abstract 1
- VBOCOLGZBIVTQB-UHFFFAOYSA-N 4-chloro-1-N-methyl-6-nitrobenzene-1,3-disulfonamide Chemical compound ClC=1C(=CC(=C(C=1)[N+](=O)[O-])S(NC)(=O)=O)S(N)(=O)=O VBOCOLGZBIVTQB-UHFFFAOYSA-N 0.000 abstract 1
- KDOWETFJBFGOOG-UHFFFAOYSA-N 5-chloro-2-nitrobenzenesulfonamide Chemical class NS(=O)(=O)C1=CC(Cl)=CC=C1[N+]([O-])=O KDOWETFJBFGOOG-UHFFFAOYSA-N 0.000 abstract 1
- ILEKCYUSYWEDPL-UHFFFAOYSA-N 6-chloro-3-(chloromethyl)-1,1-dioxo-3,4-dihydro-2h-1$l^{6},2,4-benzothiadiazine-7-sulfonamide Chemical class C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NC(CCl)NS2(=O)=O ILEKCYUSYWEDPL-UHFFFAOYSA-N 0.000 abstract 1
- XOTCKXJHVMQFRA-UHFFFAOYSA-N 6-chloro-3-nitrocyclohexa-1,5-diene-1,3-disulfonic acid Chemical compound ClC=1C(=CC(CC=1)(S(=O)(=O)O)[N+](=O)[O-])S(=O)(=O)O XOTCKXJHVMQFRA-UHFFFAOYSA-N 0.000 abstract 1
- 239000004215 Carbon black (E152) Substances 0.000 abstract 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 abstract 1
- RNPABQVCNAUEIY-GUQYYFCISA-N Germine Chemical compound O1[C@@]([C@H](CC[C@]23C)O)(O)[C@H]3C[C@@H](O)[C@@H]([C@]3(O)[C@@H](O)[C@H](O)[C@@H]4[C@]5(C)O)[C@@]12C[C@H]3[C@@H]4CN1[C@H]5CC[C@H](C)C1 RNPABQVCNAUEIY-GUQYYFCISA-N 0.000 abstract 1
- 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 abstract 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 abstract 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 abstract 1
- 229930189630 Protoveratrine Natural products 0.000 abstract 1
- HYTGGNIMZXFORS-MGYKWWNKSA-N Protoveratrine A Chemical compound O1[C@@]([C@H](CC[C@]23C)OC(=O)[C@@](C)(O)CC)(O)[C@H]3[C@@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]3[C@@]12C[C@H]1[C@H](CN2[C@@H](CC[C@H](C)C2)[C@@]2(C)O)[C@@H]2[C@@H](O)[C@H](OC(=O)[C@H](C)CC)[C@@]31O HYTGGNIMZXFORS-MGYKWWNKSA-N 0.000 abstract 1
- ZCDNRPPFBQDQHR-SSYATKPKSA-N Syrosingopine Chemical compound C1=C(OC)C(OC(=O)OCC)=C(OC)C=C1C(=O)O[C@H]1[C@H](OC)[C@@H](C(=O)OC)[C@H]2C[C@@H]3C(NC=4C5=CC=C(OC)C=4)=C5CCN3C[C@H]2C1 ZCDNRPPFBQDQHR-SSYATKPKSA-N 0.000 abstract 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 abstract 1
- 125000001931 aliphatic group Chemical group 0.000 abstract 1
- 229910052783 alkali metal Inorganic materials 0.000 abstract 1
- 230000002152 alkylating effect Effects 0.000 abstract 1
- 229910021529 ammonia Inorganic materials 0.000 abstract 1
- 239000000872 buffer Substances 0.000 abstract 1
- 239000006227 byproduct Substances 0.000 abstract 1
- 239000002775 capsule Substances 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 abstract 1
- IHJCXVZDYSXXFT-UHFFFAOYSA-N chloraminophenamide Chemical compound NC1=CC(Cl)=C(S(N)(=O)=O)C=C1S(N)(=O)=O IHJCXVZDYSXXFT-UHFFFAOYSA-N 0.000 abstract 1
- DXXUGBPKQDTBQW-UHFFFAOYSA-L chlorisondamine Chemical compound [Cl-].[Cl-].ClC1=C(Cl)C(Cl)=C(Cl)C2=C1C[N+](CC[N+](C)(C)C)(C)C2 DXXUGBPKQDTBQW-UHFFFAOYSA-L 0.000 abstract 1
- 229950002565 chlorisondamine Drugs 0.000 abstract 1
- VQKLRVZQQYVIJW-UHFFFAOYSA-N dihydralazine Chemical compound C1=CC=C2C(NN)=NN=C(NN)C2=C1 VQKLRVZQQYVIJW-UHFFFAOYSA-N 0.000 abstract 1
- 229960002877 dihydralazine Drugs 0.000 abstract 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 abstract 1
- 239000002934 diuretic Substances 0.000 abstract 1
- 230000001882 diuretic effect Effects 0.000 abstract 1
- 239000008298 dragée Substances 0.000 abstract 1
- 239000003995 emulsifying agent Substances 0.000 abstract 1
- 239000000839 emulsion Substances 0.000 abstract 1
- 150000002148 esters Chemical class 0.000 abstract 1
- RNPABQVCNAUEIY-UHFFFAOYSA-N germine Natural products O1C(C(CCC23C)O)(O)C3CC(O)C(C3(O)C(O)C(O)C4C5(C)O)C12CC3C4CN1C5CCC(C)C1 RNPABQVCNAUEIY-UHFFFAOYSA-N 0.000 abstract 1
- 229910052736 halogen Inorganic materials 0.000 abstract 1
- 150000002367 halogens Chemical class 0.000 abstract 1
- 229960002474 hydralazine Drugs 0.000 abstract 1
- 229930195733 hydrocarbon Natural products 0.000 abstract 1
- 150000002430 hydrocarbons Chemical group 0.000 abstract 1
- 239000007788 liquid Substances 0.000 abstract 1
- 229910052744 lithium Inorganic materials 0.000 abstract 1
- 230000001452 natriuretic effect Effects 0.000 abstract 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract 1
- 230000003204 osmotic effect Effects 0.000 abstract 1
- 238000007911 parenteral administration Methods 0.000 abstract 1
- 239000000546 pharmaceutical excipient Substances 0.000 abstract 1
- 239000000825 pharmaceutical preparation Substances 0.000 abstract 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 abstract 1
- 229920000642 polymer Polymers 0.000 abstract 1
- 159000000001 potassium salts Chemical class 0.000 abstract 1
- 239000003755 preservative agent Substances 0.000 abstract 1
- 230000001105 regulatory effect Effects 0.000 abstract 1
- 238000000926 separation method Methods 0.000 abstract 1
- 229910052708 sodium Inorganic materials 0.000 abstract 1
- 239000011734 sodium Substances 0.000 abstract 1
- 239000007787 solid Substances 0.000 abstract 1
- 239000000243 solution Substances 0.000 abstract 1
- 239000003381 stabilizer Substances 0.000 abstract 1
- 230000000087 stabilizing effect Effects 0.000 abstract 1
- 239000007858 starting material Substances 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
- 239000000725 suspension Substances 0.000 abstract 1
- 229950006534 syrosingopine Drugs 0.000 abstract 1
- 239000003826 tablet Substances 0.000 abstract 1
- 230000001225 therapeutic effect Effects 0.000 abstract 1
- 150000003568 thioethers Chemical class 0.000 abstract 1
- 238000009736 wetting Methods 0.000 abstract 1
- 239000000080 wetting agent Substances 0.000 abstract 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention comprises 3,4-dihydro-1,2,4-benzothiadiazine-1,1-dioxides of the formula <FORM:0885078/IV (b)/1> in which R is an isobutyl or chloromethyl group and physiologically tolerable salts thereof such as the lithium, sodium or potassium salts; and their preparation by (a) alkylating the corresponding dihydrobenzothiadiazine, unsubstituted in the 2-position with a reactive ester of methanol, e.g. dimethyl sulphate or, (b) reacting 5-chloro-2-(N-methylsulphamoyl)-4-sulphamoyl-aniline with an aldehyde R-CHO, or (c) reacting a 5-chloro-2-(N-methylsulphamoyl)-4-sulphamoyl-nitrobenzene with an aldehyde R-CHO and reducing the nitro group. In place of the aldehyde R-CHO, a polymer or reactive derivative thereof may be used. 3-Isobutyl- and 3-chloromethyl-6-chloro-7-sulphamoyl - 3,4 - dihydro - 1,2,4 - benzothiadiazine - 1,1-dioxides used as starting materials are prepared by the action of isovaleraldehyde or chloroacetaldehyde-diethyl acetal, respectively, on 5-chloro-2,4-disulphamoyl-aniline. 5 - Chloro - 2 - (N - methylsulphamoyl) - 4 - sulphamoyl aniline is made by reacting a 5-chloroaniline - 2,4 disulphonyl halide such as the chloride with methylamine and treating the resulting 5-chloro-2-(N-methylsulphamoyl)-aniline-4-sulphonyl halide, after separation of any 5 - chloro - 2, 4 - bis - (N - methylsulphamoyl) - aniline by product, with ammonia. The intermediate corresponding 5-chloro-nitrobenzene sulphonamide derivatives are similarly obtained. 5 - Chloro - nitrobenzene - 2, 4 - disulphonyl halides are made by reacting a 2,4-dihalo-5-chloro-nitrobenzene with a mercaptan R1SH or with a halide R1.Hal and thiourea (R1 being an aliphatic or araliphatic hydrocarbon group) and oxidising the resulting 5-chloro-nitrobenzene-2,4-di-R1-thioethers, e.g. with hydrogen peroxide, to 5-chloro-nitrobenzene-2,4-disulphonic acid followed by conversion to the sulphohalide with PCl5, or oxidising directly to the sulphohalide by the action of a halogen on the thioether. Specification 861,367 is referred to.ALSO:Pharmaceutical preparations having diuretic and natriuretic activity comprise a 3,4-dihydro-1,2,4 - benzothiadiazine - 1,1 - dioxide of the formula <FORM:0885078/VI/1> wherein R is an isobutyl or chloromethyl group or a physiologically tolerable salt thereof, such as an alkali metal salt (see Group IV (b)) in admixture with a pharmaceutical organic or inorganic, solid or liquid excipient for enteral, e.g. oral, or parenteral administration. The preparations suitably take the form of tablets, dragees, capsules, solutions, suspensions or emulsions and may contain preserving, stabilizing, wetting or emulsifying agents, salts for regulating the osmotic pressure, buffers and other therapeutic substances such as syringopine, germine, protoveratrine, hydralazine, dihydralazine and chlorisondamine. Specification 861,367 is referred to.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US885078XA | 1959-01-12 | 1959-01-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB885078A true GB885078A (en) | 1961-12-20 |
Family
ID=22211778
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB1139/60A Expired GB885078A (en) | 1959-01-12 | 1960-01-12 | 3:4-dihydro-1:2:4-benzothiadiazine-1:1-dioxides and process for their manufacture |
Country Status (1)
| Country | Link |
|---|---|
| GB (1) | GB885078A (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004017964A1 (en) | 2002-08-19 | 2004-03-04 | Pfizer Products Inc. | Combination therapy for hyperproliferative diseases |
| WO2007062314A2 (en) | 2005-11-23 | 2007-05-31 | Bristol-Myers Squibb Company | Heterocyclic cetp inhibitors |
| WO2008070496A2 (en) | 2006-12-01 | 2008-06-12 | Bristol-Myers Squibb Company | N- ( (3-benzyl) -2, 2- (bis-phenyl) -propan-1-amine derivatives as cetp inhibitors for the treatment of atherosclerosis and cardiovascular diseases |
| EP2392567A1 (en) | 2005-10-21 | 2011-12-07 | Bristol-Myers Squibb Company | Benzothiazine derivatives and their use as lxr modulators |
| WO2014170786A1 (en) | 2013-04-17 | 2014-10-23 | Pfizer Inc. | N-piperidin-3-ylbenzamide derivatives for treating cardiovascular diseases |
| WO2016055901A1 (en) | 2014-10-08 | 2016-04-14 | Pfizer Inc. | Substituted amide compounds |
| WO2020150473A2 (en) | 2019-01-18 | 2020-07-23 | Dogma Therapeutics, Inc. | Pcsk9 inhibitors and methods of use thereof |
-
1960
- 1960-01-12 GB GB1139/60A patent/GB885078A/en not_active Expired
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004017964A1 (en) | 2002-08-19 | 2004-03-04 | Pfizer Products Inc. | Combination therapy for hyperproliferative diseases |
| EP2392567A1 (en) | 2005-10-21 | 2011-12-07 | Bristol-Myers Squibb Company | Benzothiazine derivatives and their use as lxr modulators |
| WO2007062314A2 (en) | 2005-11-23 | 2007-05-31 | Bristol-Myers Squibb Company | Heterocyclic cetp inhibitors |
| WO2008070496A2 (en) | 2006-12-01 | 2008-06-12 | Bristol-Myers Squibb Company | N- ( (3-benzyl) -2, 2- (bis-phenyl) -propan-1-amine derivatives as cetp inhibitors for the treatment of atherosclerosis and cardiovascular diseases |
| WO2014170786A1 (en) | 2013-04-17 | 2014-10-23 | Pfizer Inc. | N-piperidin-3-ylbenzamide derivatives for treating cardiovascular diseases |
| WO2016055901A1 (en) | 2014-10-08 | 2016-04-14 | Pfizer Inc. | Substituted amide compounds |
| WO2020150473A2 (en) | 2019-01-18 | 2020-07-23 | Dogma Therapeutics, Inc. | Pcsk9 inhibitors and methods of use thereof |
| EP4470609A2 (en) | 2019-01-18 | 2024-12-04 | Astrazeneca AB | Pcsk9 inhibitors and methods of use thereof |
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