NO320367B1 - Lyofiliserte tioxantenon-antitumorformuleringer og anvendelse derav - Google Patents

Lyofiliserte tioxantenon-antitumorformuleringer og anvendelse derav Download PDF

Info

Publication number: NO320367B1
Authority: NO; Norway
Prior art keywords: amino; ethyl; lower alkyl; ch2n; methyl
Prior art date: 1995-09-18

Application number

NO19981205A

Other languages

English (en)

Norwegian (no)

Other versions

NO981205L (no

NO981205D0 (no

Inventor

Stephen Brown

Gurdial Sandhu

Original Assignee

Sanofi Synthelabo Inc

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.)

1995-09-18

Filing date

1998-03-17

Publication date

2005-11-28

1998-03-17 Application filed by Sanofi Synthelabo Inc filed Critical Sanofi Synthelabo Inc

1998-03-17 Publication of NO981205D0 publication Critical patent/NO981205D0/no

1998-05-15 Publication of NO981205L publication Critical patent/NO981205L/no

2005-11-28 Publication of NO320367B1 publication Critical patent/NO320367B1/no

Links

239000000203 mixture Substances 0.000 title claims abstract description 149
238000009472 formulation Methods 0.000 title claims abstract description 63
YRHRIQCWCFGUEQ-UHFFFAOYSA-N thioxanthen-9-one Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3SC2=C1 YRHRIQCWCFGUEQ-UHFFFAOYSA-N 0.000 title abstract description 5
230000000259 anti-tumor effect Effects 0.000 title description 6
206010028980 Neoplasm Diseases 0.000 claims abstract description 30
239000005720 sucrose Substances 0.000 claims abstract description 21
229930006000 Sucrose Natural products 0.000 claims abstract description 20
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 claims abstract description 20
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims abstract description 13
229930195725 Mannitol Natural products 0.000 claims abstract description 13
239000000594 mannitol Substances 0.000 claims abstract description 13
235000010355 mannitol Nutrition 0.000 claims abstract description 13
239000003381 stabilizer Substances 0.000 claims abstract description 12
239000002246 antineoplastic agent Substances 0.000 claims abstract description 9
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims abstract description 8
239000000872 buffer Substances 0.000 claims abstract description 8
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 88
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 68
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 64
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 59
125000000217 alkyl group Chemical group 0.000 claims description 36
125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 claims description 29
239000001257 hydrogen Substances 0.000 claims description 22
229910052739 hydrogen Inorganic materials 0.000 claims description 22
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 20
HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 18
150000002431 hydrogen Chemical class 0.000 claims description 12
-1 methoxy, hydroxy Chemical group 0.000 claims description 10
239000011780 sodium chloride Substances 0.000 claims description 10
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
238000002360 preparation method Methods 0.000 claims description 9
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
150000003839 salts Chemical class 0.000 claims description 7
229910052736 halogen Inorganic materials 0.000 claims description 6
150000002367 halogens Chemical group 0.000 claims description 6
238000004519 manufacturing process Methods 0.000 claims description 6
241000124008 Mammalia Species 0.000 claims description 5
239000002253 acid Substances 0.000 claims description 4
125000003545 alkoxy group Chemical group 0.000 claims description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
239000012453 solvate Substances 0.000 claims description 4
239000012931 lyophilized formulation Substances 0.000 claims description 2
229940001447 lactate Drugs 0.000 claims 4
CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical group C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 claims 3
239000001540 sodium lactate Substances 0.000 claims 3
229940005581 sodium lactate Drugs 0.000 claims 3
235000011088 sodium lactate Nutrition 0.000 claims 3
208000024770 Thyroid neoplasm Diseases 0.000 claims 1
125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
208000013076 thyroid tumor Diseases 0.000 claims 1
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 184
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 105
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 96
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 73
239000000243 solution Substances 0.000 description 69
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 68
239000000047 product Substances 0.000 description 64
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 49
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 42
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 42
238000000034 method Methods 0.000 description 36
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 35
JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 32
239000011541 reaction mixture Substances 0.000 description 31
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 28
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 28
235000019439 ethyl acetate Nutrition 0.000 description 28
239000007787 solid Substances 0.000 description 25
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
239000012044 organic layer Substances 0.000 description 24
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 23
229910000041 hydrogen chloride Inorganic materials 0.000 description 23
239000002904 solvent Substances 0.000 description 23
238000001035 drying Methods 0.000 description 22
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 22
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 21
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 21
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
ATHHXGZTWNVVOU-UHFFFAOYSA-N N-methylformamide Chemical compound CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 description 20
239000012267 brine Substances 0.000 description 20
238000004108 freeze drying Methods 0.000 description 19
239000000741 silica gel Substances 0.000 description 19
229910002027 silica gel Inorganic materials 0.000 description 19
239000012458 free base Substances 0.000 description 18
229910052757 nitrogen Inorganic materials 0.000 description 17
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 16
238000003860 storage Methods 0.000 description 16
230000009477 glass transition Effects 0.000 description 14
239000000377 silicon dioxide Substances 0.000 description 14
229910052938 sodium sulfate Inorganic materials 0.000 description 13
235000011152 sodium sulphate Nutrition 0.000 description 13
150000001875 compounds Chemical class 0.000 description 12
239000000706 filtrate Substances 0.000 description 12
238000003818 flash chromatography Methods 0.000 description 12
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 11
238000004440 column chromatography Methods 0.000 description 11
239000003814 drug Substances 0.000 description 11
235000019253 formic acid Nutrition 0.000 description 11
229940098779 methanesulfonic acid Drugs 0.000 description 11
230000008569 process Effects 0.000 description 11
239000011734 sodium Substances 0.000 description 11
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 10
229940079593 drug Drugs 0.000 description 10
238000001914 filtration Methods 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
238000007792 addition Methods 0.000 description 9
238000003756 stirring Methods 0.000 description 9
150000001412 amines Chemical class 0.000 description 8
238000001816 cooling Methods 0.000 description 8
YKGMKSIHIVVYKY-UHFFFAOYSA-N dabrafenib mesylate Chemical compound CS(O)(=O)=O.S1C(C(C)(C)C)=NC(C=2C(=C(NS(=O)(=O)C=3C(=CC=CC=3F)F)C=CC=2)F)=C1C1=CC=NC(N)=N1 YKGMKSIHIVVYKY-UHFFFAOYSA-N 0.000 description 8
239000003921 oil Substances 0.000 description 8
239000002244 precipitate Substances 0.000 description 8
239000000126 substance Substances 0.000 description 8
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
239000012359 Methanesulfonyl chloride Substances 0.000 description 7
229960000583 acetic acid Drugs 0.000 description 7
239000005457 ice water Substances 0.000 description 7
239000012535 impurity Substances 0.000 description 7
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 7
239000000843 powder Substances 0.000 description 7
XXJGBENTLXFVFI-UHFFFAOYSA-N 1-amino-methylene Chemical group N[CH2] XXJGBENTLXFVFI-UHFFFAOYSA-N 0.000 description 6
RPGMVOVTCDJHJS-UHFFFAOYSA-N 4-(aminomethyl)-1-[2-(diethylamino)ethylamino]thioxanthen-9-one Chemical compound S1C2=CC=CC=C2C(=O)C2=C1C(CN)=CC=C2NCCN(CC)CC RPGMVOVTCDJHJS-UHFFFAOYSA-N 0.000 description 6
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
238000004458 analytical method Methods 0.000 description 6
OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 6
238000002425 crystallisation Methods 0.000 description 6
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
NAMOLZVVTPNNTE-UHFFFAOYSA-N n-[[1-[2-(diethylamino)ethylamino]-9-oxothioxanthen-4-yl]methyl]methanesulfonamide Chemical compound S1C2=CC=CC=C2C(=O)C2=C1C(CNS(C)(=O)=O)=CC=C2NCCN(CC)CC NAMOLZVVTPNNTE-UHFFFAOYSA-N 0.000 description 6
239000000546 pharmaceutical excipient Substances 0.000 description 6
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
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239000003610 charcoal Substances 0.000 description 5
239000012043 crude product Substances 0.000 description 5
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QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 4
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AMWRITDGCCNYAT-UHFFFAOYSA-L hydroxy(oxo)manganese;manganese Chemical compound [Mn].O[Mn]=O.O[Mn]=O AMWRITDGCCNYAT-UHFFFAOYSA-L 0.000 description 4
239000000463 material Substances 0.000 description 4
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 4
238000001953 recrystallisation Methods 0.000 description 4
230000009467 reduction Effects 0.000 description 4
239000012265 solid product Substances 0.000 description 4
150000003456 sulfonamides Chemical class 0.000 description 4
NYDIVLHRZNHVFT-UHFFFAOYSA-N 1-[2-(dimethylamino)ethylamino]-9-oxothioxanthene-4-carbaldehyde Chemical compound S1C2=CC=CC=C2C(=O)C2=C1C(C=O)=CC=C2NCCN(C)C NYDIVLHRZNHVFT-UHFFFAOYSA-N 0.000 description 3
CCBOVKUJTNAZPB-UHFFFAOYSA-N 1-[3-(diethylamino)propylamino]-9-oxothioxanthene-4-carbaldehyde Chemical compound S1C2=CC=CC=C2C(=O)C2=C1C(C=O)=CC=C2NCCCN(CC)CC CCBOVKUJTNAZPB-UHFFFAOYSA-N 0.000 description 3
GPICEGFAIFWQLN-UHFFFAOYSA-N 1-[3-(diethylamino)propylamino]thioxanthen-9-one Chemical compound S1C2=CC=CC=C2C(=O)C2=C1C=CC=C2NCCCN(CC)CC GPICEGFAIFWQLN-UHFFFAOYSA-N 0.000 description 3
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WIRJDTJTGNEUAF-UHFFFAOYSA-N 3-chlorothioxanthen-9-one Chemical compound C1=CC=C2C(=O)C3=CC=C(Cl)C=C3SC2=C1 WIRJDTJTGNEUAF-UHFFFAOYSA-N 0.000 description 3
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WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
229920000858 Cyclodextrin Polymers 0.000 description 3
229920002307 Dextran Polymers 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
230000015556 catabolic process Effects 0.000 description 3
229940076286 cupric acetate Drugs 0.000 description 3
238000010438 heat treatment Methods 0.000 description 3
238000002347 injection Methods 0.000 description 3
239000007924 injection Substances 0.000 description 3
239000010410 layer Substances 0.000 description 3
239000007788 liquid Substances 0.000 description 3
KERBAAIBDHEFDD-UHFFFAOYSA-N n-ethylformamide Chemical compound CCNC=O KERBAAIBDHEFDD-UHFFFAOYSA-N 0.000 description 3
229910000104 sodium hydride Inorganic materials 0.000 description 3
239000000725 suspension Substances 0.000 description 3
PAGGKIWZPDTNCG-UHFFFAOYSA-N 1-[2-(diethylamino)ethylamino]-4-(ethylaminomethyl)thioxanthen-9-one Chemical compound S1C2=CC=CC=C2C(=O)C2=C1C(CNCC)=CC=C2NCCN(CC)CC PAGGKIWZPDTNCG-UHFFFAOYSA-N 0.000 description 2
UPQPNCOOROMTAO-UHFFFAOYSA-N 1-[2-(diethylamino)ethylamino]-4-(hydroxymethyl)-7-methoxythioxanthen-9-one Chemical compound S1C2=CC=C(OC)C=C2C(=O)C2=C1C(CO)=CC=C2NCCN(CC)CC UPQPNCOOROMTAO-UHFFFAOYSA-N 0.000 description 2
WMTNMICVHUBQRW-UHFFFAOYSA-N 1-[2-(diethylamino)ethylamino]-4-(methylaminomethyl)thioxanthen-9-one Chemical compound S1C2=CC=CC=C2C(=O)C2=C1C(CNC)=CC=C2NCCN(CC)CC WMTNMICVHUBQRW-UHFFFAOYSA-N 0.000 description 2
YJWSPUGSBXWTSA-UHFFFAOYSA-N 1-[2-(diethylamino)ethylamino]-7-methoxy-9-oxothioxanthene-4-carbaldehyde Chemical compound S1C2=CC=C(OC)C=C2C(=O)C2=C1C(C=O)=CC=C2NCCN(CC)CC YJWSPUGSBXWTSA-UHFFFAOYSA-N 0.000 description 2
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DRILSYDEPQSKEK-UHFFFAOYSA-N 1-[2-(diethylamino)ethylamino]-9-oxothioxanthene-4-carbaldehyde Chemical compound S1C2=CC=CC=C2C(=O)C2=C1C(C=O)=CC=C2NCCN(CC)CC DRILSYDEPQSKEK-UHFFFAOYSA-N 0.000 description 2
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JEJVFFQDODZHIV-UHFFFAOYSA-N 2-(3-chlorophenyl)sulfanylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1SC1=CC=CC(Cl)=C1 JEJVFFQDODZHIV-UHFFFAOYSA-N 0.000 description 2
ODHJOROUCITYNF-UHFFFAOYSA-N 2-bromo-5-methoxybenzoic acid Chemical compound COC1=CC=C(Br)C(C(O)=O)=C1 ODHJOROUCITYNF-UHFFFAOYSA-N 0.000 description 2
HYAFQMCRNCRJQJ-UHFFFAOYSA-N 2-bromo-6-chlorothioxanthen-9-one Chemical compound C1=C(Br)C=C2C(=O)C3=CC=C(Cl)C=C3SC2=C1 HYAFQMCRNCRJQJ-UHFFFAOYSA-N 0.000 description 2
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DTJVECUKADWGMO-UHFFFAOYSA-N 4-methoxybenzenesulfonyl chloride Chemical compound COC1=CC=C(S(Cl)(=O)=O)C=C1 DTJVECUKADWGMO-UHFFFAOYSA-N 0.000 description 2
CVXWBYRBQLKJGH-UHFFFAOYSA-N 5-bromo-2-(3-chlorophenyl)sulfanylbenzoic acid Chemical compound OC(=O)C1=CC(Br)=CC=C1SC1=CC=CC(Cl)=C1 CVXWBYRBQLKJGH-UHFFFAOYSA-N 0.000 description 2
JIXBMLPFMLMPBZ-UHFFFAOYSA-N 6-chloro-2-methoxythioxanthen-9-one Chemical compound ClC1=CC=C2C(=O)C3=CC(OC)=CC=C3SC2=C1 JIXBMLPFMLMPBZ-UHFFFAOYSA-N 0.000 description 2
YISDJDCPIOLYQH-UHFFFAOYSA-N 7-bromo-1-[2-(diethylamino)ethylamino]-9-oxothioxanthene-4-carbaldehyde Chemical compound S1C2=CC=C(Br)C=C2C(=O)C2=C1C(C=O)=CC=C2NCCN(CC)CC YISDJDCPIOLYQH-UHFFFAOYSA-N 0.000 description 2
FSMRDUDLFMDRRA-UHFFFAOYSA-N 7-bromo-1-[2-(diethylamino)ethylamino]thioxanthen-9-one Chemical compound S1C2=CC=C(Br)C=C2C(=O)C2=C1C=CC=C2NCCN(CC)CC FSMRDUDLFMDRRA-UHFFFAOYSA-N 0.000 description 2
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GDFHUNCQGDODEI-UHFFFAOYSA-N n-[[1-[2-(dimethylamino)ethylamino]-9-oxothioxanthen-4-yl]methyl]formamide Chemical compound S1C2=CC=CC=C2C(=O)C2=C1C(CNC=O)=CC=C2NCCN(C)C GDFHUNCQGDODEI-UHFFFAOYSA-N 0.000 description 1
ASVIZOWWEUBBPD-UHFFFAOYSA-N n-[[7-bromo-1-[2-(diethylamino)ethylamino]-9-oxothioxanthen-4-yl]methyl]formamide Chemical compound S1C2=CC=C(Br)C=C2C(=O)C2=C1C(CNC=O)=CC=C2NCCN(CC)CC ASVIZOWWEUBBPD-UHFFFAOYSA-N 0.000 description 1
PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
238000004806 packaging method and process Methods 0.000 description 1
201000008129 pancreatic ductal adenocarcinoma Diseases 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
229940127557 pharmaceutical product Drugs 0.000 description 1
238000010587 phase diagram Methods 0.000 description 1
229920001184 polypeptide Polymers 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
229940071643 prefilled syringe Drugs 0.000 description 1
238000011165 process development Methods 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
238000012545 processing Methods 0.000 description 1
238000003672 processing method Methods 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
ROSDSFDQCJNGOL-UHFFFAOYSA-N protonated dimethyl amine Natural products CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 1
238000000746 purification Methods 0.000 description 1
239000012925 reference material Substances 0.000 description 1
238000005057 refrigeration Methods 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
238000007789 sealing Methods 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
239000007790 solid phase Substances 0.000 description 1
230000003381 solubilizing effect Effects 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
239000007858 starting material Substances 0.000 description 1
235000011149 sulphuric acid Nutrition 0.000 description 1
238000012360 testing method Methods 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
230000010512 thermal transition Effects 0.000 description 1
NBOMNTLFRHMDEZ-UHFFFAOYSA-N thiosalicylic acid Chemical compound OC(=O)C1=CC=CC=C1S NBOMNTLFRHMDEZ-UHFFFAOYSA-N 0.000 description 1
229940103494 thiosalicylic acid Drugs 0.000 description 1
KZZBVWCQFFXEPH-UHFFFAOYSA-N thioxanthen-9-one dihydrochloride Chemical compound Cl.Cl.C1=CC=CC=2SC3=CC=CC=C3C(C12)=O KZZBVWCQFFXEPH-UHFFFAOYSA-N 0.000 description 1
231100000816 toxic dose Toxicity 0.000 description 1
PNQBEPDZQUOCNY-UHFFFAOYSA-N trifluoroacetyl chloride Chemical compound FC(F)(F)C(Cl)=O PNQBEPDZQUOCNY-UHFFFAOYSA-N 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
238000001665 trituration Methods 0.000 description 1
229940124549 vasodilator Drugs 0.000 description 1
239000003071 vasodilator agent Substances 0.000 description 1
238000004017 vitrification Methods 0.000 description 1
239000008215 water for injection Substances 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- 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
- A61K31/66—Phosphorus compounds
- A61K31/67—Phosphorus compounds having sulfur as a ring hetero atom
- 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
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/382—Heterocyclic compounds having sulfur as a ring hetero atom having six-membered rings, e.g. thioxanthenes
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Epidemiology (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Oil, Petroleum & Natural Gas (AREA)
Bioinformatics & Cheminformatics (AREA)
Dermatology (AREA)
Biochemistry (AREA)
Molecular Biology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicinal Preparation (AREA)
Food Preservation Except Freezing, Refrigeration, And Drying (AREA)

NO19981205A 1995-09-18 1998-03-17 Lyofiliserte tioxantenon-antitumorformuleringer og anvendelse derav NO320367B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US08/529,934 US5665760A (en)	1995-09-18	1995-09-18	Lyophilized thioxanthenone antitumor agents
PCT/IB1996/000984 WO1997010809A1 (en)	1995-09-18	1996-09-12	Lyophilized thioxanthenone antimumor agents

Publications (3)

Publication Number	Publication Date
NO981205D0 NO981205D0 (no)	1998-03-17
NO981205L NO981205L (no)	1998-05-15
NO320367B1 true NO320367B1 (no)	2005-11-28

Family

ID=24111801

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19981205A NO320367B1 (no)	1995-09-18	1998-03-17	Lyofiliserte tioxantenon-antitumorformuleringer og anvendelse derav

Country Status (19)

Country	Link
US (1)	US5665760A (pl)
EP (1)	EP0917458B1 (pl)
JP (1)	JP2001503374A (pl)
KR (1)	KR100475385B1 (pl)
CN (1)	CN1178651C (pl)
AT (1)	ATE235888T1 (pl)
AU (1)	AU716782B2 (pl)
CA (1)	CA2232444A1 (pl)
CZ (1)	CZ293433B6 (pl)
DE (1)	DE69627209T2 (pl)
DK (1)	DK0917458T3 (pl)
ES (1)	ES2196171T3 (pl)
HU (1)	HUP9900246A3 (pl)
NO (1)	NO320367B1 (pl)
NZ (1)	NZ316609A (pl)
PL (1)	PL185164B1 (pl)
PT (1)	PT917458E (pl)
RU (1)	RU2157189C2 (pl)
WO (1)	WO1997010809A1 (pl)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5952300A (en) *	1996-04-19	1999-09-14	Merck & Co., Inc.	Antifungal compositions
US6407278B2 (en) *	1998-11-16	2002-06-18	Medimmune Oncology, Inc.	Stable amorphous amifostine compositions and methods for the preparation and use of the same
GB0115893D0 (en) *	2001-06-28	2001-08-22	Sanofi Synthelabo	Formulations
US7378408B2 (en) *	2001-11-30	2008-05-27	Pfizer Inc.	Methods of treatment and formulations of cephalosporin
JP2007526329A (ja) *	2004-03-04	2007-09-13	ワイス	賦形剤の結晶化を改善するための凍結乾燥法
AU2006329849A1 (en) *	2005-12-16	2007-07-05	Wyeth	Lyophilized compositions of a triazolopyrimidine compound
WO2010056847A2 (en) *	2008-11-13	2010-05-20	Taigen Biotechnology Co., Ltd.	Lyophilization formulation

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4582851A (en) *	1984-02-06	1986-04-15	Warner-Lambert Company	Anti-bacterial 1,4-aminoalkylamino-9H-thioxanthen-9-one derivatives, compositions, and method of use therefor
US5346917A (en) *	1991-06-10	1994-09-13	Sterling Winthrop Inc.	Thioxanthenone antitumor agents
AU642596B2 (en) *	1991-06-10	1993-10-21	Sanofi-Synthelabo	Thioxanthenone antitumor agents
US5091410A (en) *	1991-06-10	1992-02-25	Sterling Winthrop Inc.	Thioxanthenone antitumor agents

1995
- 1995-09-18 US US08/529,934 patent/US5665760A/en not_active Expired - Fee Related
1996
- 1996-09-12 PT PT96929491T patent/PT917458E/pt unknown
- 1996-09-12 JP JP51253097A patent/JP2001503374A/ja not_active Ceased
- 1996-09-12 CZ CZ1998799A patent/CZ293433B6/cs not_active IP Right Cessation
- 1996-09-12 NZ NZ316609A patent/NZ316609A/xx unknown
- 1996-09-12 WO PCT/IB1996/000984 patent/WO1997010809A1/en not_active Ceased
- 1996-09-12 PL PL96325603A patent/PL185164B1/pl not_active IP Right Cessation
- 1996-09-12 AU AU68880/96A patent/AU716782B2/en not_active Ceased
- 1996-09-12 HU HU9900246A patent/HUP9900246A3/hu unknown
- 1996-09-12 RU RU98107334/14A patent/RU2157189C2/ru not_active IP Right Cessation
- 1996-09-12 ES ES96929491T patent/ES2196171T3/es not_active Expired - Lifetime
- 1996-09-12 KR KR1019980701983A patent/KR100475385B1/ko not_active Expired - Fee Related
- 1996-09-12 AT AT96929491T patent/ATE235888T1/de not_active IP Right Cessation
- 1996-09-12 CN CNB961981741A patent/CN1178651C/zh not_active Expired - Fee Related
- 1996-09-12 DK DK96929491T patent/DK0917458T3/da active
- 1996-09-12 CA CA002232444A patent/CA2232444A1/en not_active Abandoned
- 1996-09-12 EP EP96929491A patent/EP0917458B1/en not_active Expired - Lifetime
- 1996-09-12 DE DE69627209T patent/DE69627209T2/de not_active Expired - Fee Related
1998
- 1998-03-17 NO NO19981205A patent/NO320367B1/no unknown

Also Published As

Publication number	Publication date
KR100475385B1 (ko)	2006-03-23
JP2001503374A (ja)	2001-03-13
KR19990045741A (ko)	1999-06-25
HUP9900246A2 (hu)	2001-04-28
PL185164B1 (pl)	2003-03-31
ES2196171T3 (es)	2003-12-16
WO1997010809A1 (en)	1997-03-27
DE69627209T2 (de)	2004-02-19
NO981205L (no)	1998-05-15
CZ293433B6 (cs)	2004-04-14
DE69627209D1 (en)	2003-05-08
CN1201387A (zh)	1998-12-09
PT917458E (pt)	2003-08-29
RU2157189C2 (ru)	2000-10-10
DK0917458T3 (da)	2003-07-28
EP0917458B1 (en)	2003-04-02
MX9802143A (es)	1998-05-31
NO981205D0 (no)	1998-03-17
PL325603A1 (en)	1998-08-03
CZ79998A3 (cs)	1998-08-12
ATE235888T1 (de)	2003-04-15
US5665760A (en)	1997-09-09
CA2232444A1 (en)	1997-03-27
HK1016891A1 (zh)	1999-11-12
EP0917458A1 (en)	1999-05-26
HUP9900246A3 (en)	2002-12-28
CN1178651C (zh)	2004-12-08
AU716782B2 (en)	2000-03-09
AU6888096A (en)	1997-04-09
NZ316609A (en)	1999-05-28

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NL1014634C1 (nl)	2000-08-03	Zolpidemzouten.
RU2096043C1 (ru)	1997-11-20	Антигипоксическое средство и способ его получения
MXPA98002143A (es)	1998-10-23	Agentes antitumorales de tioxantenona liofilizados
US6730678B2 (en)	2004-05-04	Benzoylguanidine salt and hydrates thereof
RU2045268C1 (ru)	1995-10-10	Противогистаминное и антиаллергическое средство и способ приготовления глутамината хинуклидил-3-дифенилкарбинола в виде раствора для инъекций
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KR970003126B1 (ko)	1997-03-14	디티올란 유도체
MXPA03007192A (en)	2008-10-03	Novel benzoylguanidine salt
KR840001357B1 (ko)	1984-09-20	데카히드로퀴놀리놀 유도체의 제조방법
CN112047990A (zh)	2020-12-08	阿糖胞苷前药mb07133晶型及其应用
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NO750864L (pl)	1974-10-22
HK1135095A (en)	2010-05-28	Salts of pyrrolopyrimidinone derivatives and process for preparing the same