SK13982000A3 - 3',3'-n-bis-substituované makrolidové lhrh antagonisty - Google Patents

3',3'-n-bis-substituované makrolidové lhrh antagonisty Download PDF

Info

Publication number: SK13982000A3
Authority: SK; Slovakia
Prior art keywords: methyl; deoxy; carboxy; erythromycin; bisdemethyl
Prior art date: 1998-03-27

Application number

SK1398-2000A

Other languages

English (en)

Slovak (sk)

Inventor

Daryl R. Sauer

Fortuna Haviv

John Randolph

Nicholas A. Mort

Christopher R. Dalton

Milan Bruncko

Michele A. Kaminski

Bradley W. Crawford

Lisa Marie Frey

Jonathan Greer

Original Assignee

Abbott Laboratories

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.)

1998-03-27

Filing date

1999-03-22

Publication date

2001-04-09

1999-03-22 Application filed by Abbott Laboratories filed Critical Abbott Laboratories

2001-04-09 Publication of SK13982000A3 publication Critical patent/SK13982000A3/sk

Links

229940124041 Luteinizing hormone releasing hormone (LHRH) antagonist Drugs 0.000 title description 14
239000003120 macrolide antibiotic agent Substances 0.000 title description 8
150000001875 compounds Chemical class 0.000 claims abstract description 124
238000000034 method Methods 0.000 claims abstract description 69
230000008569 process Effects 0.000 claims abstract description 17
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
-1 3,4-dichlorophenethylamino Chemical group 0.000 claims description 236
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 186
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 170
229960003276 erythromycin Drugs 0.000 claims description 158
ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 claims description 147
229930006677 Erythromycin A Natural products 0.000 claims description 130
238000006243 chemical reaction Methods 0.000 claims description 51
125000000217 alkyl group Chemical group 0.000 claims description 38
125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 claims description 27
239000000460 chlorine Substances 0.000 claims description 25
125000000623 heterocyclic group Chemical group 0.000 claims description 25
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 21
150000003839 salts Chemical class 0.000 claims description 19
229910052739 hydrogen Inorganic materials 0.000 claims description 18
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 14
229960002626 clarithromycin Drugs 0.000 claims description 14
125000003118 aryl group Chemical group 0.000 claims description 13
125000004122 cyclic group Chemical group 0.000 claims description 13
125000003545 alkoxy group Chemical group 0.000 claims description 12
239000001257 hydrogen Substances 0.000 claims description 12
229910052740 iodine Inorganic materials 0.000 claims description 12
125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 11
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 11
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 10
239000011630 iodine Substances 0.000 claims description 10
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 claims description 10
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
239000002168 alkylating agent Substances 0.000 claims description 9
229940100198 alkylating agent Drugs 0.000 claims description 9
238000005804 alkylation reaction Methods 0.000 claims description 9
125000000753 cycloalkyl group Chemical group 0.000 claims description 9
125000006239 protecting group Chemical group 0.000 claims description 9
125000003342 alkenyl group Chemical group 0.000 claims description 8
230000029936 alkylation Effects 0.000 claims description 8
238000010520 demethylation reaction Methods 0.000 claims description 8
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
238000002360 preparation method Methods 0.000 claims description 8
239000000010 aprotic solvent Substances 0.000 claims description 7
230000017858 demethylation Effects 0.000 claims description 7
150000002148 esters Chemical class 0.000 claims description 7
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 claims description 7
125000003107 substituted aryl group Chemical group 0.000 claims description 7
241000124008 Mammalia Species 0.000 claims description 6
230000002152 alkylating effect Effects 0.000 claims description 6
230000001335 demethylating effect Effects 0.000 claims description 6
125000001424 substituent group Chemical group 0.000 claims description 6
150000001350 alkyl halides Chemical class 0.000 claims description 5
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
239000002904 solvent Substances 0.000 claims description 5
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
125000000304 alkynyl group Chemical group 0.000 claims description 4
229910052801 chlorine Inorganic materials 0.000 claims description 4
BGTOWKSIORTVQH-UHFFFAOYSA-N cyclo-pentanone Natural products O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 claims description 4
229910052731 fluorine Inorganic materials 0.000 claims description 4
150000004820 halides Chemical class 0.000 claims description 4
125000005842 heteroatom Chemical group 0.000 claims description 4
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
150000001299 aldehydes Chemical class 0.000 claims description 3
125000002877 alkyl aryl group Chemical group 0.000 claims description 3
HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 claims description 3
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
150000002431 hydrogen Chemical class 0.000 claims description 3
150000002576 ketones Chemical class 0.000 claims description 3
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
125000006433 1-ethyl cyclopropyl group Chemical group [H]C([H])([H])C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 claims description 2
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
239000003054 catalyst Substances 0.000 claims description 2
FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 claims description 2
125000001309 chloro group Chemical group Cl* 0.000 claims description 2
BGTOWKSIORTVQH-HOSYLAQJSA-N cyclopentanone Chemical group O=[13C]1CCCC1 BGTOWKSIORTVQH-HOSYLAQJSA-N 0.000 claims description 2
PQLFROTZSIMBKR-UHFFFAOYSA-N ethenyl carbonochloridate Chemical compound ClC(=O)OC=C PQLFROTZSIMBKR-UHFFFAOYSA-N 0.000 claims description 2
125000001153 fluoro group Chemical group F* 0.000 claims description 2
229910052987 metal hydride Inorganic materials 0.000 claims description 2
150000004681 metal hydrides Chemical class 0.000 claims description 2
CAEWJEXPFKNBQL-UHFFFAOYSA-N prop-2-enyl carbonochloridate Chemical compound ClC(=O)OCC=C CAEWJEXPFKNBQL-UHFFFAOYSA-N 0.000 claims description 2
239000003586 protic polar solvent Substances 0.000 claims description 2
230000002401 inhibitory effect Effects 0.000 claims 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
239000011737 fluorine Substances 0.000 claims 1
229940116736 romycin Drugs 0.000 claims 1
239000005557 antagonist Substances 0.000 abstract description 8
229940088597 hormone Drugs 0.000 abstract description 5
239000005556 hormone Substances 0.000 abstract description 5
239000003488 releasing hormone Substances 0.000 abstract description 2
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 46
238000005481 NMR spectroscopy Methods 0.000 description 40
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 33
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 29
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
235000019439 ethyl acetate Nutrition 0.000 description 19
239000011734 sodium Substances 0.000 description 19
238000004809 thin layer chromatography Methods 0.000 description 19
239000000203 mixture Substances 0.000 description 18
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
239000012267 brine Substances 0.000 description 16
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
SHQSVMDWKBRBGB-UHFFFAOYSA-N cyclobutanone Chemical compound O=C1CCC1 SHQSVMDWKBRBGB-UHFFFAOYSA-N 0.000 description 15
238000001035 drying Methods 0.000 description 15
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
MQPUAVYKVIHUJP-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)ethanamine Chemical compound NCCC1=CC=C(Cl)C(Cl)=C1 MQPUAVYKVIHUJP-UHFFFAOYSA-N 0.000 description 14
125000004432 carbon atom Chemical group C* 0.000 description 14
239000000243 solution Substances 0.000 description 13
238000012800 visualization Methods 0.000 description 13
QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 11
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
JMYVMOUINOAAPA-UHFFFAOYSA-N cyclopropanecarbaldehyde Chemical compound O=CC1CC1 JMYVMOUINOAAPA-UHFFFAOYSA-N 0.000 description 11
239000000741 silica gel Substances 0.000 description 11
229910002027 silica gel Inorganic materials 0.000 description 11
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239000007787 solid Substances 0.000 description 10
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IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
239000003163 gonadal steroid hormone Substances 0.000 description 8
239000012044 organic layer Substances 0.000 description 8
239000012074 organic phase Substances 0.000 description 8
239000000126 substance Substances 0.000 description 8
125000001984 thiazolidinyl group Chemical group 0.000 description 8
241001465754 Metazoa Species 0.000 description 7
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 7
239000000556 agonist Substances 0.000 description 7
238000001914 filtration Methods 0.000 description 7
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 6
229910052799 carbon Inorganic materials 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
229910052736 halogen Inorganic materials 0.000 description 6
150000002367 halogens Chemical class 0.000 description 6
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VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 6
DOJZSEYEQKWUSI-UHFFFAOYSA-N 1-methylcyclopropane-1-carbaldehyde Chemical group O=CC1(C)CC1 DOJZSEYEQKWUSI-UHFFFAOYSA-N 0.000 description 5
FJYXMCYYPFAUPO-UHFFFAOYSA-N 2-(3-chloro-4-fluorophenyl)ethanamine Chemical group NCCC1=CC=C(F)C(Cl)=C1 FJYXMCYYPFAUPO-UHFFFAOYSA-N 0.000 description 5
SRXFXCKTIGELTI-UHFFFAOYSA-N 2-(4-chlorophenyl)ethanamine Chemical compound NCCC1=CC=C(Cl)C=C1 SRXFXCKTIGELTI-UHFFFAOYSA-N 0.000 description 5
102000012673 Follicle Stimulating Hormone Human genes 0.000 description 5
108010079345 Follicle Stimulating Hormone Proteins 0.000 description 5
LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 5
239000002585 base Substances 0.000 description 5
AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 description 5
230000000694 effects Effects 0.000 description 5
229940028334 follicle stimulating hormone Drugs 0.000 description 5
238000009472 formulation Methods 0.000 description 5
231100000252 nontoxic Toxicity 0.000 description 5
230000003000 nontoxic effect Effects 0.000 description 5
125000006413 ring segment Chemical group 0.000 description 5
229910052717 sulfur Chemical group 0.000 description 5
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 5
SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 4
ITOFPJRDSCGOSA-KZLRUDJFSA-N (2s)-2-[[(4r)-4-[(3r,5r,8r,9s,10s,13r,14s,17r)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H](CC[C@]13C)[C@@H]2[C@@H]3CC[C@@H]1[C@H](C)CCC(=O)N[C@H](C(O)=O)CC1=CNC2=CC=CC=C12 ITOFPJRDSCGOSA-KZLRUDJFSA-N 0.000 description 4
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HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
125000003710 aryl alkyl group Chemical group 0.000 description 4
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 4
229940126543 compound 14 Drugs 0.000 description 4
229940125810 compound 20 Drugs 0.000 description 4
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 4
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125000001072 heteroaryl group Chemical group 0.000 description 4
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125000001624 naphthyl group Chemical group 0.000 description 1
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229910052759 nickel Inorganic materials 0.000 description 1
235000001968 nicotinic acid Nutrition 0.000 description 1
239000011664 nicotinic acid Substances 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-M oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC([O-])=O ZQPPMHVWECSIRJ-KTKRTIGZSA-M 0.000 description 1
229940049964 oleate Drugs 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000002892 organic cations Chemical class 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
230000016087 ovulation Effects 0.000 description 1
125000001715 oxadiazolyl group Chemical group 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
125000000160 oxazolidinyl group Chemical group 0.000 description 1
125000004043 oxo group Chemical group O=* 0.000 description 1
238000002638 palliative care Methods 0.000 description 1
WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
239000002245 particle Substances 0.000 description 1
238000005192 partition Methods 0.000 description 1
239000008188 pellet Substances 0.000 description 1
125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 description 1
JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
IUGYQRQAERSCNH-UHFFFAOYSA-M pivalate Chemical compound CC(C)(C)C([O-])=O IUGYQRQAERSCNH-UHFFFAOYSA-M 0.000 description 1
229950010765 pivalate Drugs 0.000 description 1
229920000747 poly(lactic acid) Polymers 0.000 description 1
229920001515 polyalkylene glycol Polymers 0.000 description 1
201000010065 polycystic ovary syndrome Diseases 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
239000010318 polygalacturonic acid Substances 0.000 description 1
229920002643 polyglutamic acid Polymers 0.000 description 1
239000004633 polyglycolic acid Substances 0.000 description 1
239000004626 polylactic acid Substances 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000000843 powder Substances 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
239000003223 protective agent Substances 0.000 description 1
230000000541 pulsatile effect Effects 0.000 description 1
125000002755 pyrazolinyl group Chemical group 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000001453 quaternary ammonium group Chemical group 0.000 description 1
PMZDQRJGMBOQBF-UHFFFAOYSA-N quinolin-4-ol Chemical compound C1=CC=C2C(O)=CC=NC2=C1 PMZDQRJGMBOQBF-UHFFFAOYSA-N 0.000 description 1
125000005493 quinolyl group Chemical group 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
230000009257 reactivity Effects 0.000 description 1
230000004044 response Effects 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
230000028327 secretion Effects 0.000 description 1
239000008299 semisolid dosage form Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
230000009329 sexual behaviour Effects 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
235000019345 sodium thiosulphate Nutrition 0.000 description 1
239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
230000021595 spermatogenesis Effects 0.000 description 1
230000007480 spreading Effects 0.000 description 1
238000003892 spreading Methods 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
239000000021 stimulant Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
239000001384 succinic acid Substances 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
239000011593 sulfur Chemical group 0.000 description 1
125000004434 sulfur atom Chemical group 0.000 description 1
230000001629 suppression Effects 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
238000001308 synthesis method Methods 0.000 description 1
235000015523 tannic acid Nutrition 0.000 description 1
229940033123 tannic acid Drugs 0.000 description 1
229920002258 tannic acid Polymers 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
125000000165 tricyclic carbocycle group Chemical group 0.000 description 1
PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical class CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
150000003751 zinc Chemical class 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Molecular Biology (AREA)
Medicinal Chemistry (AREA)
Biochemistry (AREA)
Pharmacology & Pharmacy (AREA)
Genetics & Genomics (AREA)
Animal Behavior & Ethology (AREA)
Biotechnology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Endocrinology (AREA)
Diabetes (AREA)
Reproductive Health (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Saccharide Compounds (AREA)

SK1398-2000A 1998-03-27 1999-03-22 3',3'-n-bis-substituované makrolidové lhrh antagonisty SK13982000A3 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US09/049,458 US5972898A (en)	1998-03-27	1998-03-27	3',3-N-bis-substituted macrolide LHRH antagonists
PCT/US1999/006250 WO1999050276A1 (fr)	1998-03-27	1999-03-22	Antagonistes de lhrh a base de macrolides 3',3'-n-bis-substitues

Publications (1)

Publication Number	Publication Date
SK13982000A3 true SK13982000A3 (sk)	2001-04-09

Family

ID=21959914

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1398-2000A SK13982000A3 (sk)	1998-03-27	1999-03-22	3',3'-n-bis-substituované makrolidové lhrh antagonisty

Country Status (18)

Country	Link
US (1)	US5972898A (fr)
EP (1)	EP1066307A1 (fr)
JP (1)	JP2002509938A (fr)
KR (1)	KR20010034699A (fr)
CN (1)	CN1303389A (fr)
AU (1)	AU3197599A (fr)
BG (1)	BG104827A (fr)
BR (1)	BR9909121A (fr)
CA (1)	CA2325519A1 (fr)
HU (1)	HUP0102522A3 (fr)
IL (1)	IL138220A0 (fr)
NO (1)	NO20004807L (fr)
NZ (1)	NZ506622A (fr)
PL (1)	PL343152A1 (fr)
SK (1)	SK13982000A3 (fr)
TR (1)	TR200002766T2 (fr)
WO (1)	WO1999050276A1 (fr)
ZA (1)	ZA200005030B (fr)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6387885B1 (en) *	1998-08-26	2002-05-14	Abbott Laboratories	3′,3′-N-bis-desmethyl-3′-N-cycloalkyl erythromycin derivatives as LHRH antagonists
US20030099715A1 (en) *	2000-03-28	2003-05-29	Schwarz Franz Xaver	Granulated particles with masked taste
EP1146051A3 (fr) *	2000-04-10	2001-10-31	Pfizer Products Inc.	Dérivées de l' érythromycine A
KR100876538B1 (ko)	2000-08-17	2008-12-31	아에테르나 젠타리스 게엠베하	Ｌｈｒｈ 길항제의 염의 제조방법
JP5314835B2 (ja)	2000-11-15	2013-10-16	昌雄菅又	子宮内膜症の予防又は治療薬
AU2003202115A1 (en)	2002-02-12	2003-09-04	Pfizer Inc.	Non-peptide compounds affecting the action of gonadotropin-releasing hormone (gnrh)
WO2003106446A1 (fr)	2002-06-13	2003-12-24	Pfizer Inc.	Agents anti-gnrh non peptidiques, compositions pharmaceutiques et procedes d'utilisation
WO2007060518A2 (fr) *	2005-11-23	2007-05-31	Ranbaxy Laboratories Limited	Dérivés de cétolide en tant qu'agents antibactériens
SG176628A1 (en)	2009-06-05	2012-01-30	Link Medicine Corp	Aminopyrrolidinone derivatives and uses thereof
AR085286A1 (es) *	2011-02-21	2013-09-18	Taisho Pharmaceutical Co Ltd	Derivado de macrolido sustituido en la posicion c-4

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS6187625A (ja) *	1984-10-05	1986-05-06	Satoshi Omura	消化管収縮運動促進剤
DE3689758T2 (de) *	1985-08-31	1994-08-18	Kitasato Inst	Erythromycinderivat und Verfahren zu dessen Herstellung.
US4742049A (en) *	1986-06-04	1988-05-03	Abbott Laboratories	Semisynthetic erythromycin antibiotics
US4920102A (en) *	1988-04-18	1990-04-24	Eli Lilly And Company	Method for treating gastrointestinal disorders
IL99995A (en) *	1990-11-21	1997-11-20	Roussel Uclaf	Erythromycin derivatives, their preparation and pharmaceutical compositions containing them
US5403923A (en) *	1990-11-28	1995-04-04	Taisho Pharmaceutical Co., Ltd.	6-0-methylerythromycin A derivatives
FR2727969B1 (fr) *	1994-12-09	1997-01-17	Roussel Uclaf	Nouveaux derives de l'erythromycine, leur procede de preparation et leur application comme medicaments
WO1997021704A1 (fr) *	1995-12-14	1997-06-19	Merck & Co., Inc.	Antagonistes de l'hormone de liberation de la gonadotropine
WO1997042206A1 (fr) *	1996-05-07	1997-11-13	Abbott Laboratories	Composes a base d'erythromycine 6-0 substituee et technique de production

1998
- 1998-03-27 US US09/049,458 patent/US5972898A/en not_active Expired - Fee Related
1999
- 1999-03-22 SK SK1398-2000A patent/SK13982000A3/sk unknown
- 1999-03-22 HU HU0102522A patent/HUP0102522A3/hu unknown
- 1999-03-22 NZ NZ506622A patent/NZ506622A/xx unknown
- 1999-03-22 EP EP99914036A patent/EP1066307A1/fr not_active Withdrawn
- 1999-03-22 KR KR1020007010704A patent/KR20010034699A/ko not_active Ceased
- 1999-03-22 PL PL99343152A patent/PL343152A1/xx unknown
- 1999-03-22 TR TR2000/02766T patent/TR200002766T2/xx unknown
- 1999-03-22 WO PCT/US1999/006250 patent/WO1999050276A1/fr not_active Ceased
- 1999-03-22 IL IL13822099A patent/IL138220A0/xx unknown
- 1999-03-22 BR BR9909121-6A patent/BR9909121A/pt not_active IP Right Cessation
- 1999-03-22 CA CA002325519A patent/CA2325519A1/fr not_active Abandoned
- 1999-03-22 JP JP2000541179A patent/JP2002509938A/ja not_active Withdrawn
- 1999-03-22 AU AU31975/99A patent/AU3197599A/en not_active Abandoned
- 1999-03-22 CN CN99806661A patent/CN1303389A/zh active Pending
2000
- 2000-09-20 ZA ZA200005030A patent/ZA200005030B/xx unknown
- 2000-09-26 NO NO20004807A patent/NO20004807L/no not_active Application Discontinuation
- 2000-10-05 BG BG104827A patent/BG104827A/xx unknown

Also Published As

Publication number	Publication date
NO20004807D0 (no)	2000-09-26
CN1303389A (zh)	2001-07-11
KR20010034699A (ko)	2001-04-25
IL138220A0 (en)	2001-10-31
WO1999050276A1 (fr)	1999-10-07
ZA200005030B (en)	2001-08-10
JP2002509938A (ja)	2002-04-02
BG104827A (en)	2001-07-31
CA2325519A1 (fr)	1999-10-07
HUP0102522A2 (hu)	2001-10-28
AU3197599A (en)	1999-10-18
US5972898A (en)	1999-10-26
NO20004807L (no)	2000-11-24
TR200002766T2 (tr)	2001-01-22
NZ506622A (en)	2003-03-28
BR9909121A (pt)	2000-12-19
HUP0102522A3 (en)	2003-08-28
PL343152A1 (en)	2001-07-30
EP1066307A1 (fr)	2001-01-10

Publication	Publication Date	Title
US6387885B1 (en)	2002-05-14	3′,3′-N-bis-desmethyl-3′-N-cycloalkyl erythromycin derivatives as LHRH antagonists
RU2126416C1 (ru)	1999-02-20	Производные эритромицина, фармацевтическая композиция на их основе, способ их получения и промежуточные соединения
WO2000012522A1 (fr)	2000-03-09	Antagonistes macrolides de l'hormone de declenchement de l'hormone luteinotrophe
AU2006300215B2 (en)	2012-06-21	Novel dihydropseudoerythromycin derivatives
IL105810A (en)	1998-12-27	History of erythromycin and the pharmaceutical preparations containing them
ES2203800T3 (es)	2004-04-16	Derivados de 3-descladinosa-2, 3-anhidroeritromicina.
ES2217579T3 (es)	2004-11-01	Derivados de eritromicina cetolidos, modificados en n-3 y sustituidos en o-6, que tiene una actividad antibacteriana.
KR850000961B1 (ko)	1985-07-02	20-아미노 마크로라이드 유도체의 제조방법
SK13982000A3 (sk)	2001-04-09	3',3'-n-bis-substituované makrolidové lhrh antagonisty
EP1066304B1 (fr)	2005-02-23	Antagonistes macrolides de l'hormone de liberation de la luteinostimuline (lhrh)
EP1007530B1 (fr)	2005-11-16	Composes a base d'erythromycine 6-0 substituee et technique de production
WO2009139181A1 (fr)	2009-11-19	Composé 10a-azalide ayant une structure de cycle à 4 chaînons
JP3228835B2 (ja)	2001-11-12	エリスロマイシンの新誘導体、それらの製造法及び薬剤としての使用
WO1999000124A1 (fr)	1999-01-07	9a-azalides, compositions a base de ces composes et procedes therapeutiques
WO1999000125A1 (fr)	1999-01-07	9a-aza-3-cetolides, compositions contenant ces composes et procedes de traitement
CZ20003527A3 (cs)	2001-01-17	3',3'-N-bis substituované makrolidové antagonisty LHRV
MXPA00009424A (en)	2001-07-31	3',3'-n-bis-substituted macrolide lhrh antagonists
HK1036284B (en)	2005-12-09	Macrolide lhrh antagonists
JPS59167598A (ja)	1984-09-21	Ｃ−２０−およびｃ−２３−修飾マクロライド誘導体類
MXPA00009423A (en)	2001-07-31	Macrolide lhrh antagonists
CZ20003528A3 (cs)	2001-01-17	Makrolidové sloučeniny působící jako antagonisté LHRH
WO1999019331A1 (fr)	1999-04-22	8a-azalides, compositions contenant de tels composes, et methodes de traitement associees
WO1998058917A1 (fr)	1998-12-30	8a-azalides, compositions contenant ces composes et methodes therapeutiques
MXPA00004227A (en)	2001-05-07	6,11-bridged erythromycin derivatives
HK1009969B (en)	2000-05-12	Erythromycin derivative