IL126839A - History of indolyl-pyrrolidinemethylpyrol, process for their preparation and pharmaceutical preparations containing them - Google Patents

History of indolyl-pyrrolidinemethylpyrol, process for their preparation and pharmaceutical preparations containing them

Info

Publication number: IL126839A
Authority: IL; Israel
Prior art keywords: methyl; pyrrol; ylidene; pyrrole; indol
Prior art date: 1997-03-11

Application number

IL12683998A

Other languages

English (en)

Hebrew (he)

Other versions

IL126839A0 (en

Original Assignee

Pharmacia & Upjohn Spa

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.)

1997-03-11

Filing date

1998-02-27

Publication date

2002-12-01

1998-02-27 Application filed by Pharmacia & Upjohn Spa filed Critical Pharmacia & Upjohn Spa

1999-09-22 Publication of IL126839A0 publication Critical patent/IL126839A0/xx

2002-12-01 Publication of IL126839A publication Critical patent/IL126839A/en

Links

238000000034 method Methods 0.000 title claims description 23
239000008194 pharmaceutical composition Substances 0.000 title claims description 14
238000002360 preparation method Methods 0.000 title claims description 13
230000008569 process Effects 0.000 title claims description 8
150000003233 pyrroles Chemical class 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 135
-1 nitro, hydroxy Chemical group 0.000 claims abstract description 77
125000003545 alkoxy group Chemical group 0.000 claims abstract description 33
125000000217 alkyl group Chemical group 0.000 claims abstract description 31
150000003839 salts Chemical class 0.000 claims abstract description 29
239000001257 hydrogen Substances 0.000 claims abstract description 26
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 26
125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 24
229910052736 halogen Inorganic materials 0.000 claims abstract description 17
150000002367 halogens Chemical class 0.000 claims abstract description 17
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 17
230000001506 immunosuppresive effect Effects 0.000 claims abstract description 15
125000003342 alkenyl group Chemical group 0.000 claims abstract description 13
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 13
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 13
125000005116 aryl carbamoyl group Chemical group 0.000 claims abstract description 10
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 9
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims abstract description 8
125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 8
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims abstract description 8
125000001424 substituent group Chemical group 0.000 claims abstract description 8
125000003806 alkyl carbonyl amino group Chemical group 0.000 claims abstract description 7
125000003118 aryl group Chemical group 0.000 claims abstract description 7
125000004104 aryloxy group Chemical group 0.000 claims abstract description 6
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 6
125000001589 carboacyl group Chemical group 0.000 claims abstract description 5
125000003358 C2-C20 alkenyl group Chemical group 0.000 claims abstract description 4
125000005196 alkyl carbonyloxy group Chemical group 0.000 claims abstract description 4
229910003827 NRaRb Inorganic materials 0.000 claims abstract description 3
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 3
MWLCANHMIJFNDV-UHFFFAOYSA-N 2-[2-(pyrrol-2-ylidenemethyl)pyrrol-1-yl]-1h-indole Chemical class C=1C=CN(C=2NC3=CC=CC=C3C=2)C=1C=C1C=CC=N1 MWLCANHMIJFNDV-UHFFFAOYSA-N 0.000 claims abstract 2
239000000203 mixture Substances 0.000 claims description 28
239000003018 immunosuppressive agent Substances 0.000 claims description 22
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
230000000694 effects Effects 0.000 claims description 15
229940125721 immunosuppressive agent Drugs 0.000 claims description 15
238000011282 treatment Methods 0.000 claims description 12
241000124008 Mammalia Species 0.000 claims description 10
239000003937 drug carrier Substances 0.000 claims description 10
239000003814 drug Substances 0.000 claims description 9
239000003795 chemical substances by application Substances 0.000 claims description 8
238000002560 therapeutic procedure Methods 0.000 claims description 8
208000009746 Adult T-Cell Leukemia-Lymphoma Diseases 0.000 claims description 7
206010001413 Adult T-cell lymphoma/leukaemia Diseases 0.000 claims description 7
229940079593 drug Drugs 0.000 claims description 7
229930105110 Cyclosporin A Natural products 0.000 claims description 5
PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims description 5
108010036949 Cyclosporine Proteins 0.000 claims description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
229960001265 ciclosporin Drugs 0.000 claims description 5
239000003085 diluting agent Substances 0.000 claims description 5
229960003444 immunosuppressant agent Drugs 0.000 claims description 5
FVQQHNOFRMIZER-UHFFFAOYSA-N CCCCCCCCCCCC1=NC(=Cc2[nH]c(cc2OC)-c2cc3ccccc3[nH]2)C=C1 Chemical compound CCCCCCCCCCCC1=NC(=Cc2[nH]c(cc2OC)-c2cc3ccccc3[nH]2)C=C1 FVQQHNOFRMIZER-UHFFFAOYSA-N 0.000 claims description 4
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 4
239000002253 acid Substances 0.000 claims description 4
230000001861 immunosuppressant effect Effects 0.000 claims description 4
239000000546 pharmaceutical excipient Substances 0.000 claims description 4
DJZFIVFZZFKKAF-UHFFFAOYSA-N C1=CC(CC)=NC1=CC1=C(OC)C=C(C=2NC3=CC=CC=C3C=2)N1 Chemical compound C1=CC(CC)=NC1=CC1=C(OC)C=C(C=2NC3=CC=CC=C3C=2)N1 DJZFIVFZZFKKAF-UHFFFAOYSA-N 0.000 claims description 3
ZJRLWSWRKMUAFA-UHFFFAOYSA-N CC1=NC(=Cc2[nH]c(cc2OCc2ccccc2)-c2cc3cc(ccc3[nH]2)C#N)C=C1 Chemical compound CC1=NC(=Cc2[nH]c(cc2OCc2ccccc2)-c2cc3cc(ccc3[nH]2)C#N)C=C1 ZJRLWSWRKMUAFA-UHFFFAOYSA-N 0.000 claims description 3
VGAHISXYOFMWEZ-UHFFFAOYSA-N CCCCCCCCCCCC1=NC(=Cc2[nH]c(cc2OC)-c2cc3cc(C)ccc3[nH]2)C=C1 Chemical compound CCCCCCCCCCCC1=NC(=Cc2[nH]c(cc2OC)-c2cc3cc(C)ccc3[nH]2)C=C1 VGAHISXYOFMWEZ-UHFFFAOYSA-N 0.000 claims description 3
MRGCHGRJEWKSEE-UHFFFAOYSA-N CCCCCCCCCCCC1=NC(=Cc2[nH]c(cc2OC)-c2cc3cc(ccc3[nH]2)C(O)=O)C=C1 Chemical compound CCCCCCCCCCCC1=NC(=Cc2[nH]c(cc2OC)-c2cc3cc(ccc3[nH]2)C(O)=O)C=C1 MRGCHGRJEWKSEE-UHFFFAOYSA-N 0.000 claims description 3
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 3
FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 3
QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 claims description 3
239000002955 immunomodulating agent Substances 0.000 claims description 3
238000002650 immunosuppressive therapy Methods 0.000 claims description 3
229960000485 methotrexate Drugs 0.000 claims description 3
RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 claims description 3
229960004866 mycophenolate mofetil Drugs 0.000 claims description 3
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims description 3
ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 claims description 3
229960002930 sirolimus Drugs 0.000 claims description 3
QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 claims description 3
QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 claims description 3
JTOKYIBTLUQVQV-QRVTZXGZSA-N (3s,6s,9s,12r,15s,18s,21s,24s,30s,33s)-30-[(1r)-1-hydroxyethyl]-33-[(e,1r,2r)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontan Chemical compound C\C=C\C[C@@H](C)[C@@H](O)[C@@H]1N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C(=O)[C@H]([C@@H](C)O)NC1=O JTOKYIBTLUQVQV-QRVTZXGZSA-N 0.000 claims description 2
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
GSOLNLHEUFGMTA-UHFFFAOYSA-N C(C1=CC=CC=C1)OC=1C=C2C=C(NC2=CC1)C=1NC(=C(C1)OC)C=C1N=C(C=C1)CCCCCCCCCCC Chemical compound C(C1=CC=CC=C1)OC=1C=C2C=C(NC2=CC1)C=1NC(=C(C1)OC)C=C1N=C(C=C1)CCCCCCCCCCC GSOLNLHEUFGMTA-UHFFFAOYSA-N 0.000 claims description 2
RRXMGIWJEVABCP-UHFFFAOYSA-N C1=CC(CCC)=NC1=CC1=C(OC)C=C(C=2NC3=CC=CC=C3C=2)N1 Chemical compound C1=CC(CCC)=NC1=CC1=C(OC)C=C(C=2NC3=CC=CC=C3C=2)N1 RRXMGIWJEVABCP-UHFFFAOYSA-N 0.000 claims description 2
XWHMTBVGMAAKSY-UHFFFAOYSA-N C1=CC(CCCC)=NC1=CC1=C(OC)C=C(C=2NC3=CC=CC=C3C=2)N1 Chemical compound C1=CC(CCCC)=NC1=CC1=C(OC)C=C(C=2NC3=CC=CC=C3C=2)N1 XWHMTBVGMAAKSY-UHFFFAOYSA-N 0.000 claims description 2
LXPUNRIGELTHJE-UHFFFAOYSA-N C1=CC(CCCCCCCCCCC)=NC1=CC1=C(OC)C=C(C=2NC3=C(CC)C=CC=C3C=2)N1 Chemical compound C1=CC(CCCCCCCCCCC)=NC1=CC1=C(OC)C=C(C=2NC3=C(CC)C=CC=C3C=2)N1 LXPUNRIGELTHJE-UHFFFAOYSA-N 0.000 claims description 2
DWGGKNONSANHKA-UHFFFAOYSA-N C1=CC(CCCCCCCCCCC)=NC1=CC1=C(OC)C=C(C=2NC3=CC(=CC=C3C=2)[N+]([O-])=O)N1 Chemical compound C1=CC(CCCCCCCCCCC)=NC1=CC1=C(OC)C=C(C=2NC3=CC(=CC=C3C=2)[N+]([O-])=O)N1 DWGGKNONSANHKA-UHFFFAOYSA-N 0.000 claims description 2
INRBPFWUWMKSTL-UHFFFAOYSA-N C1=CC(CCCCCCCCCCC)=NC1=CC1=C(OC)C=C(C=2NC3=CC=C(C=C3C=2)C#N)N1 Chemical compound C1=CC(CCCCCCCCCCC)=NC1=CC1=C(OC)C=C(C=2NC3=CC=C(C=C3C=2)C#N)N1 INRBPFWUWMKSTL-UHFFFAOYSA-N 0.000 claims description 2
ZERYUKDMARMCIC-UHFFFAOYSA-N C1=CC(CCCCCCCCCCC)=NC1=CC1=C(OC)C=C(C=2NC3=CC=C(N)C=C3C=2)N1 Chemical compound C1=CC(CCCCCCCCCCC)=NC1=CC1=C(OC)C=C(C=2NC3=CC=C(N)C=C3C=2)N1 ZERYUKDMARMCIC-UHFFFAOYSA-N 0.000 claims description 2
CXDWJFKUALDXQJ-UHFFFAOYSA-N CCCCCCCCCCCC1=NC(=Cc2[nH]c(cc2OC)-c2cc3cc(F)ccc3[nH]2)C=C1 Chemical compound CCCCCCCCCCCC1=NC(=Cc2[nH]c(cc2OC)-c2cc3cc(F)ccc3[nH]2)C=C1 CXDWJFKUALDXQJ-UHFFFAOYSA-N 0.000 claims description 2
RZFGQSLUWOLBTM-UHFFFAOYSA-N COC=1C=C(C=2NC3=CC=CC=C3C=2)NC=1C=C1C=CC(C)=N1 Chemical compound COC=1C=C(C=2NC3=CC=CC=C3C=2)NC=1C=C1C=CC(C)=N1 RZFGQSLUWOLBTM-UHFFFAOYSA-N 0.000 claims description 2
JTOKYIBTLUQVQV-UHFFFAOYSA-N Cyclosporin C Natural products CC=CCC(C)C(O)C1N(C)C(=O)C(C(C)C)N(C)C(=O)C(CC(C)C)N(C)C(=O)C(CC(C)C)N(C)C(=O)C(C)NC(=O)C(C)NC(=O)C(CC(C)C)N(C)C(=O)C(C(C)C)NC(=O)C(CC(C)C)N(C)C(=O)CN(C)C(=O)C(C(C)O)NC1=O JTOKYIBTLUQVQV-UHFFFAOYSA-N 0.000 claims description 2
206010025323 Lymphomas Diseases 0.000 claims description 2
125000005907 alkyl ester group Chemical group 0.000 claims description 2
108010019248 cyclosporin C Proteins 0.000 claims description 2
239000003862 glucocorticoid Substances 0.000 claims description 2
150000003840 hydrochlorides Chemical class 0.000 claims description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
WNWVKZTYMQWFHE-UHFFFAOYSA-N 4-ethylmorpholine Chemical group [CH2]CN1CCOCC1 WNWVKZTYMQWFHE-UHFFFAOYSA-N 0.000 claims 1
MVIAICMIDWDTFF-UHFFFAOYSA-N COC=1C=C(C=2NC3=CC=CC=C3C=2)NC=1C=C1C=CC(C(C)C)=N1 Chemical compound COC=1C=C(C=2NC3=CC=CC=C3C=2)NC=1C=C1C=CC(C(C)C)=N1 MVIAICMIDWDTFF-UHFFFAOYSA-N 0.000 claims 1
YKGMKSIHIVVYKY-UHFFFAOYSA-N dabrafenib mesylate Chemical class 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 claims 1
208000032839 leukemia Diseases 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract description 5
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 3
125000003837 (C1-C20) alkyl group Chemical group 0.000 abstract 1
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 40
239000000243 solution Substances 0.000 description 22
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
238000012360 testing method Methods 0.000 description 19
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 13
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ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
101150041968 CDC13 gene Proteins 0.000 description 11
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 11
239000002246 antineoplastic agent Substances 0.000 description 11
210000004027 cell Anatomy 0.000 description 11
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241000282412 Homo Species 0.000 description 9
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
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235000011152 sodium sulphate Nutrition 0.000 description 6
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BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
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VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
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229960001592 paclitaxel Drugs 0.000 description 1
PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
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125000000109 phenylethoxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])O* 0.000 description 1
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229920000136 polysorbate Polymers 0.000 description 1
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229940068965 polysorbates Drugs 0.000 description 1
229920002451 polyvinyl alcohol Polymers 0.000 description 1
235000019422 polyvinyl alcohol Nutrition 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
229960004618 prednisone Drugs 0.000 description 1
XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
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239000000651 prodrug Substances 0.000 description 1
230000009682 proliferation pathway Effects 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
239000000377 silicon dioxide Substances 0.000 description 1
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CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
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229940079832 sodium starch glycolate Drugs 0.000 description 1
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239000002904 solvent Substances 0.000 description 1
241000894007 species Species 0.000 description 1
108010042747 stallimycin Proteins 0.000 description 1
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239000005720 sucrose Substances 0.000 description 1
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239000004094 surface-active agent Substances 0.000 description 1
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208000024891 symptom Diseases 0.000 description 1
230000002195 synergetic effect Effects 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
OWPIFQXNMLDXKW-UHFFFAOYSA-N tert-butyl indole-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC(C)(C)C)C=CC2=C1 OWPIFQXNMLDXKW-UHFFFAOYSA-N 0.000 description 1
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
238000011285 therapeutic regimen Methods 0.000 description 1
230000004797 therapeutic response Effects 0.000 description 1
229940104230 thymidine Drugs 0.000 description 1
206010043778 thyroiditis Diseases 0.000 description 1
208000005057 thyrotoxicosis Diseases 0.000 description 1
UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
229960000303 topotecan Drugs 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
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125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 1
CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Substances C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 1
229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
125000000297 undecanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000005065 undecenyl group Chemical group C(=CCCCCCCCCC)* 0.000 description 1
125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
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229960003048 vinblastine Drugs 0.000 description 1
JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection

Landscapes

Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Life Sciences & Earth Sciences (AREA)
Immunology (AREA)
General Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Transplantation (AREA)
Hematology (AREA)
Oncology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Saccharide Compounds (AREA)
Pyrrole Compounds (AREA)

IL12683998A 1997-03-11 1998-02-27 History of indolyl-pyrrolidinemethylpyrol, process for their preparation and pharmaceutical preparations containing them IL126839A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB9705035.5A GB9705035D0 (en)	1997-03-11	1997-03-11	Indolyl-pyrrolydenemethylpyrrole derivatives and process for their preparation
PCT/EP1998/001285 WO1998040380A1 (en)	1997-03-11	1998-02-27	Indolyl-pyrrolydenemethylpyrrole derivatives and process for their preparation

Publications (2)

Publication Number	Publication Date
IL126839A0 IL126839A0 (en)	1999-09-22
IL126839A true IL126839A (en)	2002-12-01

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IL12683998A IL126839A (en)	1997-03-11	1998-02-27	History of indolyl-pyrrolidinemethylpyrol, process for their preparation and pharmaceutical preparations containing them

Country Status (26)

Country	Link
US (1)	US6071947A (es)
EP (1)	EP0909271B1 (es)
JP (1)	JP2000510873A (es)
KR (1)	KR20000010913A (es)
CN (1)	CN1089763C (es)
AR (1)	AR011964A1 (es)
AT (1)	ATE206118T1 (es)
AU (1)	AU740583B2 (es)
BR (1)	BR9805938A (es)
CA (1)	CA2253588A1 (es)
DE (1)	DE69801795T2 (es)
DK (1)	DK0909271T3 (es)
EA (1)	EA001055B1 (es)
ES (1)	ES2165150T3 (es)
GB (1)	GB9705035D0 (es)
HU (1)	HUP0003614A3 (es)
IL (1)	IL126839A (es)
MY (1)	MY117159A (es)
NO (1)	NO316754B1 (es)
NZ (1)	NZ333015A (es)
PL (1)	PL329808A1 (es)
PT (1)	PT909271E (es)
TW (1)	TW568911B (es)
UA (1)	UA56169C2 (es)
WO (1)	WO1998040380A1 (es)
ZA (1)	ZA981976B (es)

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Publication number	Priority date	Publication date	Assignee	Title
EP1229934B1 (en)	1999-10-01	2014-03-05	Immunogen, Inc.	Compositions and methods for treating cancer using immunoconjugates and chemotherapeutic agents
US20040014987A1 (en)	2000-01-26	2004-01-22	Gemin X Biotechnologies Inc.	Pyrrole-Type compounds, compositions, and methods for treating cancer or viral diseases
US6407244B1 (en)	2000-01-26	2002-06-18	Gemin X Biotechnologies Inc.	Pyrrole-type compounds, compositions, and methods for treating cancer or viral diseases
DE10038699A1 (de) *	2000-07-31	2002-02-14	Michael Sittinger	Mittel zur Verringrung der Abstoßungsreaktionen bei Transplantaten
US7144912B2 (en)	2001-07-18	2006-12-05	Gemin X Biotechnologies Inc.	Pyrrole-type compounds, compositions, and methods for treating cancer, treating viral diseases and causing immunosuppression
WO2003064617A2 (en) *	2002-01-30	2003-08-07	Montana State University	Pestalotiopsis microsporia isolates and compounds derived therefrom
US7968569B2 (en) *	2002-05-17	2011-06-28	Celgene Corporation	Methods for treatment of multiple myeloma using 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione
PL1644363T3 (pl) *	2003-05-30	2012-07-31	Gemin X Pharmaceuticals Canada Inc	Związki triheterocykliczne, kompozycje i metody leczenia raka
WO2006115509A2 (en)	2004-06-24	2006-11-02	Novartis Vaccines And Diagnostics Inc.	Small molecule immunopotentiators and assays for their detection
WO2006069441A1 (en)	2004-12-28	2006-07-06	Gemin X Biotechnologies Inc.	Dipyrrole compounds, compositions, and methods for treating cancer or viral diseases
WO2006089397A1 (en) *	2005-02-22	2006-08-31	Gemin X Biotechnologies Inc.	Methods for treating arthritis using triheterocyclic compounds
DE102005025225A1 (de)	2005-06-01	2006-12-07	Sanofi-Aventis Deutschland Gmbh	Verfahren zur Herstellung von 2-(2-Amino-pyrimidin-4-yl)-1H-indol-5-carbonsäure-derivaten
US20080051400A1 (en) *	2006-07-06	2008-02-28	Gemin X Biotechnologies Inc.	Methods for treating or preventing anemia or thrombocytopenia using a triheterocyclic compound
CN113845524B (zh) *	2021-10-29	2023-11-07	四川农业大学	一种螺吡咯吲哚酮类化合物及其制备方法和应用

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JPS61280429A (ja) *	1985-06-06	1986-12-11	Chugai Pharmaceut Co Ltd	免疫抑制剤
EP0695301B1 (en) *	1993-04-22	1996-10-30	Pfizer Limited	Indole derivatives as 5-ht1-like agonists for use in migraine
GB9326284D0 (en) *	1993-12-23	1994-02-23	Erba Carlo Spa	Pyrrolydenemethyl-derivatives and process for their preparation
GB9603212D0 (en) *	1996-02-15	1996-04-17	Pharmacia Spa	Process for the preparation of 2,2'-bipyrrolyl-pyrromethane derivatives

1997
- 1997-03-11 GB GBGB9705035.5A patent/GB9705035D0/en active Pending
1998
- 1998-02-27 CN CN98800469A patent/CN1089763C/zh not_active Expired - Fee Related
- 1998-02-27 HU HU0003614A patent/HUP0003614A3/hu unknown
- 1998-02-27 EA EA199801004A patent/EA001055B1/ru not_active IP Right Cessation
- 1998-02-27 AT AT98913665T patent/ATE206118T1/de not_active IP Right Cessation
- 1998-02-27 JP JP10539188A patent/JP2000510873A/ja not_active Withdrawn
- 1998-02-27 ES ES98913665T patent/ES2165150T3/es not_active Expired - Lifetime
- 1998-02-27 US US09/147,249 patent/US6071947A/en not_active Expired - Fee Related
- 1998-02-27 IL IL12683998A patent/IL126839A/en not_active IP Right Cessation
- 1998-02-27 UA UA98126509A patent/UA56169C2/uk unknown
- 1998-02-27 EP EP98913665A patent/EP0909271B1/en not_active Expired - Lifetime
- 1998-02-27 DE DE69801795T patent/DE69801795T2/de not_active Expired - Fee Related
- 1998-02-27 WO PCT/EP1998/001285 patent/WO1998040380A1/en not_active Ceased
- 1998-02-27 KR KR1019980709060A patent/KR20000010913A/ko not_active Abandoned
- 1998-02-27 AU AU68283/98A patent/AU740583B2/en not_active Ceased
- 1998-02-27 BR BR9805938-6A patent/BR9805938A/pt not_active IP Right Cessation
- 1998-02-27 CA CA002253588A patent/CA2253588A1/en not_active Abandoned
- 1998-02-27 DK DK98913665T patent/DK0909271T3/da active
- 1998-02-27 NZ NZ333015A patent/NZ333015A/xx unknown
- 1998-02-27 PL PL98329808A patent/PL329808A1/xx unknown
- 1998-02-27 PT PT98913665T patent/PT909271E/pt unknown
- 1998-03-07 TW TW087103345A patent/TW568911B/zh active
- 1998-03-09 ZA ZA981976A patent/ZA981976B/xx unknown
- 1998-03-11 AR ARP980101075A patent/AR011964A1/es unknown
- 1998-03-11 MY MYPI98001060A patent/MY117159A/en unknown
- 1998-11-10 NO NO19985248A patent/NO316754B1/no unknown

Also Published As

Publication number	Publication date
AU6828398A (en)	1998-09-29
TW568911B (en)	2004-01-01
IL126839A0 (en)	1999-09-22
EA199801004A1 (ru)	1999-06-24
CN1222911A (zh)	1999-07-14
KR20000010913A (ko)	2000-02-25
PL329808A1 (en)	1999-04-12
EP0909271A1 (en)	1999-04-21
MY117159A (en)	2004-05-31
PT909271E (pt)	2002-03-28
EP0909271B1 (en)	2001-09-26
HUP0003614A2 (hu)	2001-10-28
CN1089763C (zh)	2002-08-28
UA56169C2 (uk)	2003-05-15
DE69801795D1 (de)	2001-10-31
NO985248L (no)	1999-01-11
ATE206118T1 (de)	2001-10-15
EA001055B1 (ru)	2000-08-28
HUP0003614A3 (en)	2003-04-28
BR9805938A (pt)	1999-08-31
NO316754B1 (no)	2004-04-26
DK0909271T3 (da)	2002-01-28
US6071947A (en)	2000-06-06
GB9705035D0 (en)	1997-04-30
CA2253588A1 (en)	1998-09-17
NO985248D0 (no)	1998-11-10
DE69801795T2 (de)	2002-05-23
JP2000510873A (ja)	2000-08-22
WO1998040380A1 (en)	1998-09-17
NZ333015A (en)	2000-04-28
ES2165150T3 (es)	2002-03-01
ZA981976B (en)	1998-09-09
AR011964A1 (es)	2000-09-13
AU740583B2 (en)	2001-11-08

Publication	Publication Date	Title
US5691334A (en)	1997-11-25	Pyrrolydenemethyl-derivatives and process for their preparation
EP0909271B1 (en)	2001-09-26	Indolyl-pyrrolydenemethylpyrrole derivatives and process for their preparation
US7732482B2 (en)	2010-06-08	Compound from Antrodia camphorata and the use thereof
US5385918A (en)	1995-01-31	Aminomethylene-peptides as immunosuppressants
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