CA1051429A - Composes de 6h-pyrimido (1,2-c) (1,3,5) benzothiadiazoiques - Google Patents

Composes de 6h-pyrimido (1,2-c) (1,3,5) benzothiadiazoiques

Info

Publication number: CA1051429A
Authority: CA; Canada
Prior art keywords: compound; carbons; pyrimido; bromo; alkyl
Prior art date: 1973-07-26
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

Application number

CA203,661A

Other languages

English (en)

Other versions

CA203661S (en

Inventor

Harry L. Yale

Ramesh B. Petigara

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.)

ER Squibb and Sons LLC

Original Assignee

ER Squibb and Sons LLC

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.)

1973-07-26

Filing date

1974-06-28

Publication date

1979-03-27

1974-06-28 Application filed by ER Squibb and Sons LLC filed Critical ER Squibb and Sons LLC

1979-03-27 Application granted granted Critical

1979-03-27 Publication of CA1051429A publication Critical patent/CA1051429A/fr

Status Expired legal-status Critical Current

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 59
-1 mono-substituted phenyl Chemical group 0.000 claims abstract description 16
125000000217 alkyl group Chemical group 0.000 claims abstract description 11
229910052794 bromium Inorganic materials 0.000 claims abstract description 10
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 10
239000001257 hydrogen Substances 0.000 claims abstract description 10
229910052801 chlorine Inorganic materials 0.000 claims abstract description 8
150000003839 salts Chemical class 0.000 claims abstract description 8
150000002431 hydrogen Chemical class 0.000 claims abstract description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 4
238000004519 manufacturing process Methods 0.000 claims abstract description 3
238000000034 method Methods 0.000 claims description 34
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 9
239000000460 chlorine Chemical group 0.000 claims description 9
229910052783 alkali metal Inorganic materials 0.000 claims description 5
238000010438 heat treatment Methods 0.000 claims description 5
SWPNNCQFJFWAIU-UHFFFAOYSA-N 6h-pyrimido[1,2-c][1,3,5]benzothiadiazepine Chemical compound C1SC2=CC=CC=C2N=C2N=CC=CN12 SWPNNCQFJFWAIU-UHFFFAOYSA-N 0.000 claims description 4
239000010949 copper Substances 0.000 claims description 4
229910052802 copper Inorganic materials 0.000 claims description 4
KAOYLRLQZXRRBD-UHFFFAOYSA-N 1,2,3-benzothiadiazepine Chemical compound S1N=NC=CC2=CC=CC=C12 KAOYLRLQZXRRBD-UHFFFAOYSA-N 0.000 claims description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
229910000288 alkali metal carbonate Inorganic materials 0.000 claims description 3
150000008041 alkali metal carbonates Chemical class 0.000 claims description 3
150000001340 alkali metals Chemical class 0.000 claims description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
125000001309 chloro group Chemical group Cl* 0.000 claims description 3
QGVFEFRCCDGRTC-UHFFFAOYSA-N 3-chloro-6h-pyrimido[1,2-c][1,3,5]benzothiadiazepine Chemical compound C1SC2=CC=CC=C2N=C2N=CC(Cl)=CN21 QGVFEFRCCDGRTC-UHFFFAOYSA-N 0.000 claims description 2
150000008044 alkali metal hydroxides Chemical class 0.000 claims description 2
229910000318 alkali metal phosphate Inorganic materials 0.000 claims description 2
239000007858 starting material Substances 0.000 claims 4
KTXJPNFNLLKGNC-UHFFFAOYSA-N 11-propyl-11,12-dihydropyrimido[2,1-b][6,1,3]benzothiadiazocine Chemical compound S1C(CCC)CN2C=CC=NC2=NC2=CC=CC=C21 KTXJPNFNLLKGNC-UHFFFAOYSA-N 0.000 claims 2
239000003054 catalyst Substances 0.000 claims 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract description 9
239000000543 intermediate Substances 0.000 abstract description 6
LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 abstract description 6
229910052731 fluorine Inorganic materials 0.000 abstract description 5
229910052736 halogen Inorganic materials 0.000 abstract description 5
150000002367 halogens Chemical group 0.000 abstract description 5
239000003158 myorelaxant agent Substances 0.000 abstract description 5
229940035363 muscle relaxants Drugs 0.000 abstract description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 3
125000003545 alkoxy group Chemical group 0.000 abstract description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 abstract description 2
210000003169 central nervous system Anatomy 0.000 abstract description 2
229910052740 iodine Inorganic materials 0.000 abstract description 2
230000004936 stimulating effect Effects 0.000 abstract description 2
125000001424 substituent group Chemical group 0.000 abstract description 2
239000000203 mixture Substances 0.000 description 28
239000000047 product Substances 0.000 description 25
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
239000000243 solution Substances 0.000 description 19
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 12
238000010992 reflux Methods 0.000 description 12
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 11
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
229910000027 potassium carbonate Inorganic materials 0.000 description 8
239000011734 sodium Substances 0.000 description 8
229910052708 sodium Inorganic materials 0.000 description 8
159000000000 sodium salts Chemical class 0.000 description 8
125000000446 sulfanediyl group Chemical group *S* 0.000 description 8
229920002261 Corn starch Polymers 0.000 description 7
238000006243 chemical reaction Methods 0.000 description 7
239000008120 corn starch Substances 0.000 description 7
230000000694 effects Effects 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
235000011181 potassium carbonates Nutrition 0.000 description 7
239000007787 solid Substances 0.000 description 7
LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 6
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 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
IDXKTTNFXPPXJY-UHFFFAOYSA-N pyrimidin-1-ium;chloride Chemical compound Cl.C1=CN=CN=C1 IDXKTTNFXPPXJY-UHFFFAOYSA-N 0.000 description 6
238000003786 synthesis reaction Methods 0.000 description 6
125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 5
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 5
239000002775 capsule Substances 0.000 description 5
239000002904 solvent Substances 0.000 description 5
238000003756 stirring Methods 0.000 description 5
YUQUNWNSQDULTI-UHFFFAOYSA-N 2-bromobenzenethiol Chemical compound SC1=CC=CC=C1Br YUQUNWNSQDULTI-UHFFFAOYSA-N 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 4
239000002253 acid Substances 0.000 description 4
235000019359 magnesium stearate Nutrition 0.000 description 4
238000002360 preparation method Methods 0.000 description 4
238000010626 work up procedure Methods 0.000 description 4
XDWAKHMDRKLOEU-UHFFFAOYSA-N 1-bromo-2-(chloromethylsulfanyl)benzene Chemical compound ClCSC1=CC=CC=C1Br XDWAKHMDRKLOEU-UHFFFAOYSA-N 0.000 description 3
DOENFIYZEDUWRR-UHFFFAOYSA-N 2-bromo-4-chlorobenzenethiol Chemical compound SC1=CC=C(Cl)C=C1Br DOENFIYZEDUWRR-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 3
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
WINXNKPZLFISPD-UHFFFAOYSA-M Saccharin sodium Chemical group [Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 WINXNKPZLFISPD-UHFFFAOYSA-M 0.000 description 3
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
239000004480 active ingredient Substances 0.000 description 3
239000003513 alkali Substances 0.000 description 3
150000001448 anilines Chemical class 0.000 description 3
239000000975 dye Substances 0.000 description 3
239000008187 granular material Substances 0.000 description 3
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
229910000041 hydrogen chloride Inorganic materials 0.000 description 3
239000008101 lactose Substances 0.000 description 3
239000000463 material Substances 0.000 description 3
239000003921 oil Substances 0.000 description 3
238000001953 recrystallisation Methods 0.000 description 3
KKVTYAVXTDIPAP-UHFFFAOYSA-M sodium;methanesulfonate Chemical compound [Na+].CS([O-])(=O)=O KKVTYAVXTDIPAP-UHFFFAOYSA-M 0.000 description 3
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 3
239000000725 suspension Substances 0.000 description 3
239000006188 syrup Substances 0.000 description 3
235000020357 syrup Nutrition 0.000 description 3
RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical class SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
239000008096 xylene Substances 0.000 description 3
DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 2
KVNYFPKFSJIPBJ-UHFFFAOYSA-N 1,2-diethylbenzene Chemical compound CCC1=CC=CC=C1CC KVNYFPKFSJIPBJ-UHFFFAOYSA-N 0.000 description 2
IBYHHJPAARCAIE-UHFFFAOYSA-N 1-bromo-2-chloroethane Chemical compound ClCCBr IBYHHJPAARCAIE-UHFFFAOYSA-N 0.000 description 2
XMBHHHIZJLPPFO-UHFFFAOYSA-N 1-bromo-2-chloropentane Chemical compound CCCC(Cl)CBr XMBHHHIZJLPPFO-UHFFFAOYSA-N 0.000 description 2
RGGIMPYCVUNPGX-UHFFFAOYSA-N 3-bromo-4-methylbenzenethiol Chemical compound CC1=CC=C(S)C=C1Br RGGIMPYCVUNPGX-UHFFFAOYSA-N 0.000 description 2
229920001817 Agar Polymers 0.000 description 2
241000416162 Astragalus gummifer Species 0.000 description 2
241000167854 Bourreria succulenta Species 0.000 description 2
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 2
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
229910020656 PBr5 Inorganic materials 0.000 description 2
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 2
229920001615 Tragacanth Polymers 0.000 description 2
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
239000008272 agar Substances 0.000 description 2
238000013019 agitation Methods 0.000 description 2
150000005005 aminopyrimidines Chemical class 0.000 description 2
230000000844 anti-bacterial effect Effects 0.000 description 2
150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
239000002585 base Substances 0.000 description 2
125000001246 bromo group Chemical group Br* 0.000 description 2
MGWVXCJVOQWUQG-UHFFFAOYSA-N bromomethanesulfonic acid Chemical compound OS(=O)(=O)CBr MGWVXCJVOQWUQG-UHFFFAOYSA-N 0.000 description 2
HUCVOHYBFXVBRW-UHFFFAOYSA-M caesium hydroxide Chemical compound [OH-].[Cs+] HUCVOHYBFXVBRW-UHFFFAOYSA-M 0.000 description 2
235000019693 cherries Nutrition 0.000 description 2
239000007958 cherry flavor Substances 0.000 description 2
KRIFIIWBVJKVST-UHFFFAOYSA-N chloro(chloromethylsulfanyl)methane Chemical class ClCSCCl KRIFIIWBVJKVST-UHFFFAOYSA-N 0.000 description 2
125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 2
ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 2
230000003247 decreasing effect Effects 0.000 description 2
239000012153 distilled water Substances 0.000 description 2
150000002170 ethers Chemical class 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
235000003599 food sweetener Nutrition 0.000 description 2
238000009472 formulation Methods 0.000 description 2
CZPWVGJYEJSRLH-UHFFFAOYSA-O hydron;pyrimidine Chemical compound C1=CN=C[NH+]=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-O 0.000 description 2
DOUHZFSGSXMPIE-UHFFFAOYSA-N hydroxidooxidosulfur(.) Chemical compound [O]SO DOUHZFSGSXMPIE-UHFFFAOYSA-N 0.000 description 2
239000004615 ingredient Substances 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
230000000813 microbial effect Effects 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
239000006187 pill Substances 0.000 description 2
239000003755 preservative agent Substances 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 2
229940081974 saccharin Drugs 0.000 description 2
235000019204 saccharin Nutrition 0.000 description 2
239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 2
235000010234 sodium benzoate Nutrition 0.000 description 2
239000004299 sodium benzoate Substances 0.000 description 2
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
239000000600 sorbitol Substances 0.000 description 2
239000008107 starch Substances 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
239000003765 sweetening agent Substances 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
150000003573 thiols Chemical class 0.000 description 2
239000011701 zinc Substances 0.000 description 2
FYEACNUNMARUMV-UHFFFAOYSA-N (2-bromo-4-chlorophenyl)sulfanylmethanesulfonic acid Chemical class OS(=O)(=O)CSC1=CC=C(Cl)C=C1Br FYEACNUNMARUMV-UHFFFAOYSA-N 0.000 description 1
KZZRPBWEAJJBRC-UHFFFAOYSA-N (2-bromo-5-chlorophenyl)sulfanylmethanesulfonic acid Chemical compound OS(=O)(=O)CSC1=CC(Cl)=CC=C1Br KZZRPBWEAJJBRC-UHFFFAOYSA-N 0.000 description 1
OGNVQLDIPUXYDH-ZPKKHLQPSA-N (2R,3R,4S)-3-(2-methylpropanoylamino)-4-(4-phenyltriazol-1-yl)-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid Chemical compound CC(C)C(=O)N[C@H]1[C@H]([C@H](O)[C@H](O)CO)OC(C(O)=O)=C[C@@H]1N1N=NC(C=2C=CC=CC=2)=C1 OGNVQLDIPUXYDH-ZPKKHLQPSA-N 0.000 description 1
FGOANQWFWXSPKL-UHFFFAOYSA-N 1,1-dibromo-2-methylpropane Chemical compound CC(C)C(Br)Br FGOANQWFWXSPKL-UHFFFAOYSA-N 0.000 description 1
RELMFMZEBKVZJC-UHFFFAOYSA-N 1,2,3-trichlorobenzene Chemical compound ClC1=CC=CC(Cl)=C1Cl RELMFMZEBKVZJC-UHFFFAOYSA-N 0.000 description 1
OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 1
BBWJDRFYQUGOMG-UHFFFAOYSA-N 1-[(2-bromophenyl)sulfanylmethyl]pyrimidin-1-ium-2-amine;chloride Chemical compound [Cl-].NC1=NC=CC=[N+]1CSC1=CC=CC=C1Br BBWJDRFYQUGOMG-UHFFFAOYSA-N 0.000 description 1
NHVLWRXSFMPBAA-UHFFFAOYSA-N 1-[(2-bromophenyl)sulfanylmethyl]pyrimidin-2-imine Chemical compound BrC1=CC=CC=C1SCN1C(=N)N=CC=C1 NHVLWRXSFMPBAA-UHFFFAOYSA-N 0.000 description 1
XNCYORQKHZNODF-UHFFFAOYSA-N 1-bromo-2-(2-chloropentylsulfanyl)benzene Chemical compound CCCC(Cl)CSC1=CC=CC=C1Br XNCYORQKHZNODF-UHFFFAOYSA-N 0.000 description 1
125000005273 2-acetoxybenzoic acid group Chemical group 0.000 description 1
GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
SCVJRXQHFJXZFZ-KVQBGUIXSA-N 2-amino-9-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purine-6-thione Chemical compound C1=2NC(N)=NC(=S)C=2N=CN1[C@H]1C[C@H](O)[C@@H](CO)O1 SCVJRXQHFJXZFZ-KVQBGUIXSA-N 0.000 description 1
QKRJIXSZTKOFTD-UHFFFAOYSA-N 2-bromo-4-(trifluoromethyl)aniline Chemical compound NC1=CC=C(C(F)(F)F)C=C1Br QKRJIXSZTKOFTD-UHFFFAOYSA-N 0.000 description 1
HEMCLYRICUKDRS-UHFFFAOYSA-N 2-bromo-4-chloro-1-(chloromethylsulfanyl)benzene Chemical compound ClCSC1=CC=C(Cl)C=C1Br HEMCLYRICUKDRS-UHFFFAOYSA-N 0.000 description 1
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ZQYHKXMMUISUNM-UHFFFAOYSA-N 2H-pyrimido[4,5-g]thiadiazocine Chemical class S1NN=CC=CC2=C1C=NC=N2 ZQYHKXMMUISUNM-UHFFFAOYSA-N 0.000 description 1
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235000021317 phosphate Nutrition 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 description 1
239000011591 potassium Substances 0.000 description 1
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235000015320 potassium carbonate Nutrition 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
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UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
BATMYWDOUUWCJE-UHFFFAOYSA-N pyrimidin-1-ium;bromide Chemical compound Br.C1=CN=CN=C1 BATMYWDOUUWCJE-UHFFFAOYSA-N 0.000 description 1
WMJXFYUXYMJFOD-UHFFFAOYSA-N pyrimido[4,5-i][1,2,3]benzothiadiazepine Chemical class S1N=NC=CC2=C1C1=C(C=C2)N=CN=C1 WMJXFYUXYMJFOD-UHFFFAOYSA-N 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
239000000376 reactant Substances 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
239000004208 shellac Substances 0.000 description 1
ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
229940113147 shellac Drugs 0.000 description 1
235000013874 shellac Nutrition 0.000 description 1
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
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BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
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239000009637 wintergreen oil Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1

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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/01—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and halogen atoms, or nitro or nitroso groups bound to the same carbon skeleton
- C07C323/09—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and halogen atoms, or nitro or nitroso groups bound to the same carbon skeleton having sulfur atoms of thio groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/64—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and sulfur atoms, not being part of thio groups, bound to the same carbon skeleton
- C07C323/66—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and sulfur atoms, not being part of thio groups, bound to the same carbon skeleton containing sulfur atoms of sulfo, esterified sulfo or halosulfonyl groups, bound to the carbon skeleton
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom

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)
Agricultural Chemicals And Associated Chemicals (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

CA203,661A 1973-07-26 1974-06-28 Composes de 6h-pyrimido (1,2-c) (1,3,5) benzothiadiazoiques Expired CA1051429A (fr)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US382802A US3875162A (en)	1973-07-26	1973-07-26	Certain 6H-pyrimido{8 1,2-c{9 {8 1,3,5{9 benzothiadiaza compounds

Publications (1)

Publication Number	Publication Date
CA1051429A true CA1051429A (fr)	1979-03-27

Family

ID=23510466

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA203,661A Expired CA1051429A (fr)	1973-07-26	1974-06-28	Composes de 6h-pyrimido (1,2-c) (1,3,5) benzothiadiazoiques

Country Status (6)

Country	Link
US (1)	US3875162A (fr)
JP (1)	JPS5041892A (fr)
CA (1)	CA1051429A (fr)
DE (1)	DE2435382A1 (fr)
FR (1)	FR2238491B1 (fr)
GB (1)	GB1476684A (fr)

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Publication number	Priority date	Publication date	Assignee	Title
US3966733A (en) *	1973-07-26	1976-06-29	E. R. Squibb & Sons, Inc.	Intermediates for certain benzothiadiazepine and benzothiadiazocine compounds
RU2683325C2 (ru)	2009-02-05	2019-03-28	Иммьюноджен, Инк.	Новые производные бензодиазепина
JP5826863B2 (ja)	2011-02-15	2015-12-02	イミュノジェン・インコーポレーテッド	細胞傷害性ベンゾジアゼピン誘導体
HK1211208A1 (zh)	2012-08-22	2016-05-20	Immunogen, Inc.	細胞毒性苯並二氮呯衍生物
WO2016036804A1 (fr)	2014-09-03	2016-03-10	Immunogen, Inc.	Dérivés de benzodiazépine cytotoxique
AU2015311987B2 (en)	2014-09-03	2020-06-04	Immunogen, Inc.	Cytotoxic benzodiazepine derivatives
WO2018195243A1 (fr)	2017-04-20	2018-10-25	Immunogen, Inc.	Dérivés de benzodiazépine cytotoxiques et leurs conjugués
IL305224B2 (en)	2017-04-20	2024-09-01	Immunogen Inc	Methods of preparing indolinobenzodiazepine derivatives
US11793885B2 (en)	2017-12-28	2023-10-24	Immunogen, Inc.	Substituted benzo[5,6][1,4]diazepino[1,2-a]indoles for the treatment of proliferative disorders
CN113661172A (zh)	2019-03-29	2021-11-16	伊缪诺金公司	用于抑制异常细胞生长或治疗增生性疾病的细胞毒性双苯并二氮杂䓬衍生物及其与细胞结合剂的缀合物

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Publication number	Priority date	Publication date	Assignee	Title
CH530412A (de) *	1968-07-15	1972-11-15	Ciba Geigy Ag	Verfahren zur Herstellung von (1)Benzothieno-(2,3-d)pyrimidinen
GB1275804A (en) *	1969-07-03	1972-05-24	Seperic	Improvements in or relating to new sulphur containing derivatives of pyrimidine, their preparation and their applications
US3704303A (en) *	1971-03-17	1972-11-28	American Home Prod	6,7,8,9 - tetrahydropyrimido(2,1-b) - benzothiazole-6-carboxylic acid,alkyl esters

1973
- 1973-07-26 US US382802A patent/US3875162A/en not_active Expired - Lifetime
1974
- 1974-06-28 CA CA203,661A patent/CA1051429A/fr not_active Expired
- 1974-07-03 GB GB2952174A patent/GB1476684A/en not_active Expired
- 1974-07-23 DE DE2435382A patent/DE2435382A1/de not_active Withdrawn
- 1974-07-26 JP JP49086507A patent/JPS5041892A/ja active Pending
- 1974-07-26 FR FR7426130A patent/FR2238491B1/fr not_active Expired

Also Published As

Publication number	Publication date
FR2238491A1 (fr)	1975-02-21
FR2238491B1 (fr)	1978-07-28
GB1476684A (en)	1977-06-16
US3875162A (en)	1975-04-01
JPS5041892A (fr)	1975-04-16
DE2435382A1 (de)	1975-02-13

Publication	Publication Date	Title
KR850000890B1 (ko)	1985-06-26	삼-치환 이미다졸 유도체의 제조방법
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CA1051429A (fr)	1979-03-27	Composes de 6h-pyrimido (1,2-c) (1,3,5) benzothiadiazoiques
US5990311A (en)	1999-11-23	Process for preparation of pyrimidine derivatives
US4546179A (en)	1985-10-08	Process for preparing sulfonylureas
EP0424125A2 (fr)	1991-04-24	Dérivés d'aralkylamine, leur méthode de préparation et fongicides les contenant
KR920001466B1 (ko)	1992-02-14	락탐 유도체 및 그의 제조방법
CS198297B2 (en)	1980-05-30	Method of producing derivatives of urea
HU209890B (en)	1994-11-28	Process for producing n-substituted 2-aminomethyl-2,3-dihydro-pyrano[2,3-b]pyridine derivatives
US3995042A (en)	1976-11-30	Pyridine containing compounds
US3966733A (en)	1976-06-29	Intermediates for certain benzothiadiazepine and benzothiadiazocine compounds
US4062846A (en)	1977-12-13	Hydroxy pyrimido compounds
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US5420140A (en)	1995-05-30	Difluorinated quinolones useful for treating bacterial infections
IL31802A (en)	1972-09-28	(p-amino alkyl phenylsulphonyl)-2-imino-imidazolidine derivatives and process for their preparation
US3965101A (en)	1976-06-22	1-(O-Bromo-phenoxyalkyl)-1,2-dihydro-2-iminopyrimidines
US3857850A (en)	1974-12-31	Pyridobenzothiadiazepine compounds
KR920007497B1 (ko)	1992-09-04	Lo/co 억제 벤즈옥사졸론
EP0624585B1 (fr)	1999-08-18	Procédé de préparation de 2-(4-(4-(4-chloro-1-pyrazolyl)butyl) 1-pipérazinyl)pyrimidine
US3957799A (en)	1976-05-18	Sulfur containing amino and imino pyridines
US3946025A (en)	1976-03-23	Process for preparing 6H-pyrido[1,2-c][1,3,5]benzothiadiazepines and benzooxadiazepines and derivatives
RU2032679C1 (ru)	1995-04-10	Производные бензатиазинов
CA1051885A (fr)	1979-04-03	Composes therapeutiques et leurs intermediaires
CA1051427A (fr)	1979-03-27	6-h-pyrimido- (1,2-c) (1,3,5) benzoxadiazepines