NO309428B1 - Fremgangsmåte for fast fase-syntese av en nona- og dekapeptid LH-RH analog - Google Patents

Fremgangsmåte for fast fase-syntese av en nona- og dekapeptid LH-RH analog Download PDF

Info

Publication number: NO309428B1
Authority: NO; Norway
Prior art keywords: serine; harg; side chain; protecting group; amino
Prior art date: 1990-02-20

Application number

NO910664A

Other languages

English (en)

Norwegian (no)

Other versions

NO910664D0 (no

NO910664L (no

Inventor

Jr John J Nestor

Natalie L Mcclure

Humberto Arzeno

Original Assignee

Syntex 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.)

1990-02-20

Filing date

1991-02-19

Publication date

2001-01-29

1991-02-19 Application filed by Syntex Inc filed Critical Syntex Inc

1991-02-19 Publication of NO910664D0 publication Critical patent/NO910664D0/no

1991-08-21 Publication of NO910664L publication Critical patent/NO910664L/no

2001-01-29 Publication of NO309428B1 publication Critical patent/NO309428B1/no

Links

XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical class C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 title claims abstract description 42
238000010532 solid phase synthesis reaction Methods 0.000 title claims abstract description 13
238000000034 method Methods 0.000 title claims description 45
150000001413 amino acids Chemical class 0.000 claims abstract description 51
MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims abstract description 34
MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims abstract description 31
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims abstract description 20
HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims abstract description 19
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 67
108090000765 processed proteins & peptides Proteins 0.000 claims description 55
125000006239 protecting group Chemical group 0.000 claims description 46
102000004196 processed proteins & peptides Human genes 0.000 claims description 28
-1 t-butyldimethylsilyl protecting group Chemical group 0.000 claims description 24
229920001184 polypeptide Polymers 0.000 claims description 21
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 20
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 19
229910000041 hydrogen chloride Inorganic materials 0.000 claims description 19
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 17
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 17
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 10
125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 claims description 10
MTCFGRXMJLQNBG-UWTATZPHSA-N D-Serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 claims description 8
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 8
QIVBCDIJIAJPQS-SECBINFHSA-N D-tryptophane Chemical compound C1=CC=C2C(C[C@@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-SECBINFHSA-N 0.000 claims description 6
WQGWDDDVZFFDIG-UHFFFAOYSA-N pyrogallol Chemical compound OC1=CC=CC(O)=C1O WQGWDDDVZFFDIG-UHFFFAOYSA-N 0.000 claims description 6
HQMLIDZJXVVKCW-UWTATZPHSA-N (2r)-2-aminopropanamide Chemical compound C[C@@H](N)C(N)=O HQMLIDZJXVVKCW-UWTATZPHSA-N 0.000 claims description 4
ROHFNLRQFUQHCH-RXMQYKEDSA-N D-leucine Chemical compound CC(C)C[C@@H](N)C(O)=O ROHFNLRQFUQHCH-RXMQYKEDSA-N 0.000 claims description 4
BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical compound NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 claims description 4
HNDVDQJCIGZPNO-RXMQYKEDSA-N D-histidine Chemical compound OC(=O)[C@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-RXMQYKEDSA-N 0.000 claims description 3
238000003786 synthesis reaction Methods 0.000 abstract description 35
230000015572 biosynthetic process Effects 0.000 abstract description 33
239000012351 deprotecting agent Substances 0.000 abstract description 8
235000001014 amino acid Nutrition 0.000 description 45
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
229920005989 resin Polymers 0.000 description 36
239000011347 resin Substances 0.000 description 36
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
230000008878 coupling Effects 0.000 description 24
238000010168 coupling process Methods 0.000 description 24
238000005859 coupling reaction Methods 0.000 description 24
239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 19
101000904177 Clupea pallasii Gonadoliberin-1 Proteins 0.000 description 18
101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 18
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 15
238000010511 deprotection reaction Methods 0.000 description 15
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 13
229910000040 hydrogen fluoride Inorganic materials 0.000 description 12
150000003839 salts Chemical class 0.000 description 12
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 11
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 9
238000004519 manufacturing process Methods 0.000 description 9
239000000243 solution Substances 0.000 description 9
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 8
238000003776 cleavage reaction Methods 0.000 description 8
230000007017 scission Effects 0.000 description 8
239000004475 Arginine Substances 0.000 description 7
108010021717 Nafarelin Proteins 0.000 description 7
235000011054 acetic acid Nutrition 0.000 description 7
239000000556 agonist Substances 0.000 description 7
238000007098 aminolysis reaction Methods 0.000 description 7
238000005915 ammonolysis reaction Methods 0.000 description 7
239000002474 gonadorelin antagonist Substances 0.000 description 7
RWHUEXWOYVBUCI-ITQXDASVSA-N nafarelin Chemical compound C([C@@H](C(=O)N[C@H](CC=1C=C2C=CC=CC2=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 RWHUEXWOYVBUCI-ITQXDASVSA-N 0.000 description 7
238000002360 preparation method Methods 0.000 description 7
239000007787 solid Substances 0.000 description 7
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
239000005557 antagonist Substances 0.000 description 6
238000004128 high performance liquid chromatography Methods 0.000 description 6
239000012535 impurity Substances 0.000 description 6
229960002333 nafarelin Drugs 0.000 description 6
239000002253 acid Substances 0.000 description 5
239000003795 chemical substances by application Substances 0.000 description 5
150000001875 compounds Chemical class 0.000 description 5
239000000203 mixture Substances 0.000 description 5
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 5
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
125000000539 amino acid group Chemical group 0.000 description 4
229910021529 ammonia Inorganic materials 0.000 description 4
230000008901 benefit Effects 0.000 description 4
238000006243 chemical reaction Methods 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
KJOZJSGOIJQCGA-UHFFFAOYSA-N dichloromethane;2,2,2-trifluoroacetic acid Chemical compound ClCCl.OC(=O)C(F)(F)F KJOZJSGOIJQCGA-UHFFFAOYSA-N 0.000 description 4
PMPYSSMGWFNAAQ-UHFFFAOYSA-N dichloromethane;n,n-diethylethanamine Chemical compound ClCCl.CCN(CC)CC PMPYSSMGWFNAAQ-UHFFFAOYSA-N 0.000 description 4
125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 4
230000006340 racemization Effects 0.000 description 4
238000004007 reversed phase HPLC Methods 0.000 description 4
239000012047 saturated solution Substances 0.000 description 4
239000002904 solvent Substances 0.000 description 4
238000012360 testing method Methods 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
125000001433 C-terminal amino-acid group Chemical group 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
229920001577 copolymer Polymers 0.000 description 3
230000000694 effects Effects 0.000 description 3
230000008030 elimination Effects 0.000 description 3
238000003379 elimination reaction Methods 0.000 description 3
125000002883 imidazolyl group Chemical group 0.000 description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
239000012071 phase Substances 0.000 description 3
230000008569 process Effects 0.000 description 3
239000000047 product Substances 0.000 description 3
235000018102 proteins Nutrition 0.000 description 3
108090000623 proteins and genes Proteins 0.000 description 3
102000004169 proteins and genes Human genes 0.000 description 3
238000011160 research Methods 0.000 description 3
238000007086 side reaction Methods 0.000 description 3
239000007790 solid phase Substances 0.000 description 3
ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 3
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 3
BPYLRGKEIUPMRJ-MRVPVSSYSA-N (2r)-3-[(2-methylpropan-2-yl)oxy]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC[C@H](C(O)=O)NC(=O)OC(C)(C)C BPYLRGKEIUPMRJ-MRVPVSSYSA-N 0.000 description 2
CNBUSIJNWNXLQQ-NSHDSACASA-N (2s)-3-(4-hydroxyphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 CNBUSIJNWNXLQQ-NSHDSACASA-N 0.000 description 2
125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 2
MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 2
CHRJZRDFSQHIFI-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;styrene Chemical compound C=CC1=CC=CC=C1.C=CC1=CC=CC=C1C=C CHRJZRDFSQHIFI-UHFFFAOYSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
108010037003 Buserelin Proteins 0.000 description 2
150000008574 D-amino acids Chemical group 0.000 description 2
RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
COLNVLDHVKWLRT-MRVPVSSYSA-N D-phenylalanine Chemical compound OC(=O)[C@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-MRVPVSSYSA-N 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
239000004471 Glycine Substances 0.000 description 2
108010069236 Goserelin Proteins 0.000 description 2
BLCLNMBMMGCOAS-URPVMXJPSA-N Goserelin Chemical compound C([C@@H](C(=O)N[C@H](COC(C)(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NNC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 BLCLNMBMMGCOAS-URPVMXJPSA-N 0.000 description 2
229910004373 HOAc Inorganic materials 0.000 description 2
150000008575 L-amino acids Chemical class 0.000 description 2
ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
MDXGYYOJGPFFJL-QMMMGPOBSA-N N(alpha)-t-butoxycarbonyl-L-leucine Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)OC(C)(C)C MDXGYYOJGPFFJL-QMMMGPOBSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
RZKYEQDPDZUERB-UHFFFAOYSA-N Pindone Chemical group C1=CC=C2C(=O)C(C(=O)C(C)(C)C)C(=O)C2=C1 RZKYEQDPDZUERB-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
159000000021 acetate salts Chemical class 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
238000013459 approach Methods 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
230000004071 biological effect Effects 0.000 description 2
CUWODFFVMXJOKD-UVLQAERKSA-N buserelin Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](COC(C)(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 CUWODFFVMXJOKD-UVLQAERKSA-N 0.000 description 2
229960002719 buserelin Drugs 0.000 description 2
210000004899 c-terminal region Anatomy 0.000 description 2
TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
229960002913 goserelin Drugs 0.000 description 2
230000003054 hormonal effect Effects 0.000 description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
230000006872 improvement Effects 0.000 description 2
JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical compound C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 description 2
238000002955 isolation Methods 0.000 description 2
230000014759 maintenance of location Effects 0.000 description 2
239000000463 material Substances 0.000 description 2
PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical class C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 2
238000000746 purification Methods 0.000 description 2
239000000377 silicon dioxide Substances 0.000 description 2
238000001228 spectrum Methods 0.000 description 2
239000010891 toxic waste Substances 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
238000005406 washing Methods 0.000 description 2
JLBCSWWZSSVXRQ-SNVBAGLBSA-N (2r)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-pyridin-3-ylpropanoic acid Chemical compound CC(C)(C)OC(=O)N[C@@H](C(O)=O)CC1=CC=CN=C1 JLBCSWWZSSVXRQ-SNVBAGLBSA-N 0.000 description 1
QVHJQCGUWFKTSE-RXMQYKEDSA-N (2r)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound OC(=O)[C@@H](C)NC(=O)OC(C)(C)C QVHJQCGUWFKTSE-RXMQYKEDSA-N 0.000 description 1
WXYGVKADAIJGHB-ZDUSSCGKSA-N (2s)-3-(1h-indol-2-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound C1=CC=C2NC(C[C@H](NC(=O)OC(C)(C)C)C(O)=O)=CC2=C1 WXYGVKADAIJGHB-ZDUSSCGKSA-N 0.000 description 1
DCLJSEPKYJSEHW-HNNXBMFYSA-N (2s)-3-[1-(4-methylphenyl)sulfonylimidazol-4-yl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1C=C(C[C@H](NC(=O)OC(C)(C)C)C(O)=O)N=C1 DCLJSEPKYJSEHW-HNNXBMFYSA-N 0.000 description 1
FHOAKXBXYSJBGX-YFKPBYRVSA-N (2s)-3-hydroxy-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@@H](CO)C(O)=O FHOAKXBXYSJBGX-YFKPBYRVSA-N 0.000 description 1
RNJYCKOVJHNKQQ-QMMMGPOBSA-N (2s)-6-(diaminomethylideneazaniumyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoate Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CCCCNC(N)=N RNJYCKOVJHNKQQ-QMMMGPOBSA-N 0.000 description 1
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 description 1
125000003287 1H-imidazol-4-ylmethyl group Chemical group [H]N1C([H])=NC(C([H])([H])[*])=C1[H] 0.000 description 1
125000001917 2,4-dinitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1*)[N+]([O-])=O)[N+]([O-])=O 0.000 description 1
VRPJIFMKZZEXLR-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid Chemical compound CC(C)(C)OC(=O)NCC(O)=O VRPJIFMKZZEXLR-UHFFFAOYSA-N 0.000 description 1
KWPQTFXULUUCGD-UHFFFAOYSA-N 3,4,5,7,8,9,10,10a-octahydropyrido[1,2-a][1,4]diazepine Chemical class C1CCN=CC2CCCCN21 KWPQTFXULUUCGD-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
229930195711 D-Serine Natural products 0.000 description 1
QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 1
RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
GJKXGJCSJWBJEZ-XRSSZCMZSA-N Deslorelin Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CNC2=CC=CC=C12 GJKXGJCSJWBJEZ-XRSSZCMZSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
108010016626 Dipeptides Proteins 0.000 description 1
201000009273 Endometriosis Diseases 0.000 description 1
239000001263 FEMA 3042 Substances 0.000 description 1
KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
239000007836 KH2PO4 Substances 0.000 description 1
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
108010000817 Leuprolide Proteins 0.000 description 1
102000009151 Luteinizing Hormone Human genes 0.000 description 1
108010073521 Luteinizing Hormone Proteins 0.000 description 1
NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
229920002230 Pectic acid Polymers 0.000 description 1
LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 description 1
108010020346 Polyglutamic Acid Proteins 0.000 description 1
239000004793 Polystyrene Substances 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
206010060862 Prostate cancer Diseases 0.000 description 1
208000000236 Prostatic Neoplasms Diseases 0.000 description 1
229920005654 Sephadex Polymers 0.000 description 1
239000012507 Sephadex™ Substances 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 1
108010050144 Triptorelin Pamoate Proteins 0.000 description 1
QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
230000021736 acetylation Effects 0.000 description 1
238000006640 acetylation reaction Methods 0.000 description 1
230000009471 action Effects 0.000 description 1
230000010933 acylation Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
238000005377 adsorption chromatography Methods 0.000 description 1
230000002411 adverse Effects 0.000 description 1
235000004279 alanine Nutrition 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
229960001126 alginic acid Drugs 0.000 description 1
150000004781 alginic acids Chemical class 0.000 description 1
150000003973 alkyl amines Chemical class 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
LFVGISIMTYGQHF-UHFFFAOYSA-N ammonium dihydrogen phosphate Chemical compound [NH4+].OP(O)([O-])=O LFVGISIMTYGQHF-UHFFFAOYSA-N 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
238000006664 bond formation reaction Methods 0.000 description 1
230000005587 bubbling Effects 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
ZMCUDHNSHCRDBT-UHFFFAOYSA-M caesium bicarbonate Chemical compound [Cs+].OC([O-])=O ZMCUDHNSHCRDBT-UHFFFAOYSA-M 0.000 description 1
150000001718 carbodiimides Chemical class 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
239000008112 carboxymethyl-cellulose Substances 0.000 description 1
229920001429 chelating resin Polymers 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
238000011210 chromatographic step Methods 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
238000011109 contamination Methods 0.000 description 1
239000007822 coupling agent Substances 0.000 description 1
230000006378 damage Effects 0.000 description 1
238000006356 dehydrogenation reaction Methods 0.000 description 1
108700025485 deslorelin Proteins 0.000 description 1
229960005408 deslorelin Drugs 0.000 description 1
UNXNGGMLCSMSLH-UHFFFAOYSA-N dihydrogen phosphate;triethylazanium Chemical compound OP(O)(O)=O.CCN(CC)CC UNXNGGMLCSMSLH-UHFFFAOYSA-N 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
239000012153 distilled water Substances 0.000 description 1
238000001035 drying Methods 0.000 description 1
230000009977 dual effect Effects 0.000 description 1
230000007613 environmental effect Effects 0.000 description 1
239000003344 environmental pollutant Substances 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
230000004720 fertilization Effects 0.000 description 1
239000012467 final product Substances 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
235000011087 fumaric acid Nutrition 0.000 description 1
LRBQNJMCXXYXIU-QWKBTXIPSA-N gallotannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@H]2[C@@H]([C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-QWKBTXIPSA-N 0.000 description 1
239000000174 gluconic acid Substances 0.000 description 1
235000012208 gluconic acid Nutrition 0.000 description 1
125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
229940088597 hormone Drugs 0.000 description 1
239000005556 hormone Substances 0.000 description 1
230000002209 hydrophobic effect Effects 0.000 description 1
238000005342 ion exchange Methods 0.000 description 1
238000004255 ion exchange chromatography Methods 0.000 description 1
231100001231 less toxic Toxicity 0.000 description 1
GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 description 1
229960004338 leuprorelin Drugs 0.000 description 1
229940040129 luteinizing hormone Drugs 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
235000019796 monopotassium phosphate Nutrition 0.000 description 1
UQKAOOAFEFCDGT-UHFFFAOYSA-N n,n-dimethyloctan-1-amine Chemical compound CCCCCCCCN(C)C UQKAOOAFEFCDGT-UHFFFAOYSA-N 0.000 description 1
229960004309 nafarelin acetate Drugs 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
125000002347 octyl 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])[H] 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
150000002923 oximes Chemical class 0.000 description 1
125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
238000004810 partition chromatography Methods 0.000 description 1
125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 description 1
238000010647 peptide synthesis reaction Methods 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
231100000719 pollutant Toxicity 0.000 description 1
239000010318 polygalacturonic acid Substances 0.000 description 1
229920002643 polyglutamic acid Polymers 0.000 description 1
229920002223 polystyrene Polymers 0.000 description 1
229920003053 polystyrene-divinylbenzene Polymers 0.000 description 1
GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
230000002028 premature Effects 0.000 description 1
238000003825 pressing Methods 0.000 description 1
239000003223 protective agent Substances 0.000 description 1
230000009467 reduction Effects 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
238000000638 solvent extraction Methods 0.000 description 1
238000001179 sorption measurement Methods 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
235000015523 tannic acid Nutrition 0.000 description 1
229920002258 tannic acid Polymers 0.000 description 1
229940033123 tannic acid Drugs 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000004448 titration Methods 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
230000002110 toxicologic effect Effects 0.000 description 1
231100000027 toxicology Toxicity 0.000 description 1
238000005809 transesterification reaction Methods 0.000 description 1
VXKHXGOKWPXYNA-PGBVPBMZSA-N triptorelin Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 VXKHXGOKWPXYNA-PGBVPBMZSA-N 0.000 description 1
229960004824 triptorelin Drugs 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/06—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length using protecting groups or activating agents
- C07K1/061—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length using protecting groups or activating agents using protecting groups
- C07K1/065—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length using protecting groups or activating agents using protecting groups for hydroxy functions, not being part of carboxy functions
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/23—Luteinising hormone-releasing hormone [LHRH]; Related peptides

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Genetics & Genomics (AREA)
Biophysics (AREA)
General Health & Medical Sciences (AREA)
Biochemistry (AREA)
Medicinal Chemistry (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Life Sciences & Earth Sciences (AREA)
Endocrinology (AREA)
Analytical Chemistry (AREA)
Peptides Or Proteins (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Bipolar Integrated Circuits (AREA)
Liquid Developers In Electrophotography (AREA)
Amplifiers (AREA)
Escalators And Moving Walkways (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
Electrophonic Musical Instruments (AREA)
Magnetic Resonance Imaging Apparatus (AREA)
Investigating Or Analysing Biological Materials (AREA)
Bidet-Like Cleaning Device And Other Flush Toilet Accessories (AREA)
Measurement And Recording Of Electrical Phenomena And Electrical Characteristics Of The Living Body (AREA)
Fuses (AREA)
Semiconductor Integrated Circuits (AREA)
Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Curing Cements, Concrete, And Artificial Stone (AREA)
Variable-Direction Aerials And Aerial Arrays (AREA)
Golf Clubs (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Diaphragms For Electromechanical Transducers (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

NO910664A 1990-02-20 1991-02-19 Fremgangsmåte for fast fase-syntese av en nona- og dekapeptid LH-RH analog NO309428B1 (no)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US48242890A	1990-02-20	1990-02-20

Publications (3)

Publication Number	Publication Date
NO910664D0 NO910664D0 (no)	1991-02-19
NO910664L NO910664L (no)	1991-08-21
NO309428B1 true NO309428B1 (no)	2001-01-29

Family

ID=23916033

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO910664A NO309428B1 (no)	1990-02-20	1991-02-19	Fremgangsmåte for fast fase-syntese av en nona- og dekapeptid LH-RH analog

Country Status (18)

Country	Link
EP (1)	EP0443532B1 (fr)
JP (1)	JP2927978B2 (fr)
KR (1)	KR0152276B1 (fr)
AT (1)	ATE107931T1 (fr)
AU (1)	AU639751B2 (fr)
CA (1)	CA2036657C (fr)
DE (1)	DE69102659T2 (fr)
DK (1)	DK0443532T3 (fr)
ES (1)	ES2057624T3 (fr)
FI (1)	FI102538B1 (fr)
HK (1)	HK43097A (fr)
HU (1)	HU208158B (fr)
IE (1)	IE71945B1 (fr)
NO (1)	NO309428B1 (fr)
NZ (1)	NZ237159A (fr)
PH (1)	PH31062A (fr)
PT (1)	PT96807B (fr)
ZA (1)	ZA911233B (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN104231055A (zh)	2013-06-18	2014-12-24	深圳翰宇药业股份有限公司	加尼瑞克前体以及由其制备醋酸加尼瑞克的方法
KR101971418B1 (ko) *	2017-06-30	2019-04-24	애니젠 주식회사	고세렐린의 제조 방법

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4301066A (en) *	1980-05-08	1981-11-17	American Home Products Corp.	Preparation of (D-Trp 6)-LH-RH via the heptapeptide H-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH2
US4632979A (en) *	1984-06-18	1986-12-30	Tulane Educational Fund	Therapeutic LHRH analogs
US4677193A (en) *	1985-02-22	1987-06-30	The Salk Institute For Biological Studies	Peptides containing an aliphatic-aromatic ketone side chain
US4800191A (en) *	1987-07-17	1989-01-24	Schally Andrew Victor	LHRH antagonists

1991
- 1991-02-19 DE DE69102659T patent/DE69102659T2/de not_active Expired - Lifetime
- 1991-02-19 KR KR1019910002623A patent/KR0152276B1/ko not_active Expired - Lifetime
- 1991-02-19 CA CA002036657A patent/CA2036657C/fr not_active Expired - Lifetime
- 1991-02-19 NZ NZ237159A patent/NZ237159A/en unknown
- 1991-02-19 PT PT96807A patent/PT96807B/pt not_active IP Right Cessation
- 1991-02-19 PH PH42022A patent/PH31062A/en unknown
- 1991-02-19 DK DK91102370.3T patent/DK0443532T3/da active
- 1991-02-19 IE IE55691A patent/IE71945B1/en not_active IP Right Cessation
- 1991-02-19 HU HU91543A patent/HU208158B/hu unknown
- 1991-02-19 NO NO910664A patent/NO309428B1/no not_active IP Right Cessation
- 1991-02-19 ZA ZA911233A patent/ZA911233B/xx unknown
- 1991-02-19 EP EP91102370A patent/EP0443532B1/fr not_active Expired - Lifetime
- 1991-02-19 FI FI910788A patent/FI102538B1/fi active
- 1991-02-19 AU AU71176/91A patent/AU639751B2/en not_active Expired
- 1991-02-19 AT AT91102370T patent/ATE107931T1/de not_active IP Right Cessation
- 1991-02-19 ES ES91102370T patent/ES2057624T3/es not_active Expired - Lifetime
- 1991-02-20 JP JP3026462A patent/JP2927978B2/ja not_active Expired - Lifetime
1997
- 1997-04-03 HK HK43097A patent/HK43097A/en not_active IP Right Cessation

Also Published As

Publication number	Publication date
CA2036657A1 (fr)	1991-08-21
FI102538B (fi)	1998-12-31
EP0443532B1 (fr)	1994-06-29
PH31062A (en)	1998-02-05
JP2927978B2 (ja)	1999-07-28
DK0443532T3 (da)	1994-07-25
EP0443532A2 (fr)	1991-08-28
AU7117691A (en)	1991-08-22
HU208158B (en)	1993-08-30
IE71945B1 (en)	1997-03-12
HK43097A (en)	1997-04-11
NO910664D0 (no)	1991-02-19
ES2057624T3 (es)	1994-10-16
PT96807A (pt)	1991-10-31
NO910664L (no)	1991-08-21
FI910788A0 (fi)	1991-02-19
FI910788L (fi)	1991-08-21
CA2036657C (fr)	2003-02-11
PT96807B (pt)	1998-07-31
JPH04211096A (ja)	1992-08-03
HU910543D0 (en)	1991-09-30
KR0152276B1 (ko)	1998-10-01
NZ237159A (en)	1992-11-25
HUT57234A (en)	1991-11-28
AU639751B2 (en)	1993-08-05
ZA911233B (en)	1992-10-28
IE910556A1 (en)	1991-08-28
DE69102659T2 (de)	1995-02-23
KR910021411A (ko)	1991-12-20
ATE107931T1 (de)	1994-07-15
FI102538B1 (fi)	1998-12-31
DE69102659D1 (de)	1994-08-04
EP0443532A3 (en)	1992-02-26

Legal Events

Date	Code	Title	Description
2011-03-07	MK1K	Patent expired

Publication	Publication Date	Title
US5110904A (en)	1992-05-05	Lhrh analogs
AU744812B2 (en)	2002-03-07	Process for the preparation of resin-bound cyclic peptides
EP2448956B1 (fr)	2018-05-16	Synthèse de peptide en phase solide d'alcools peptidiques
EP1773870A2 (fr)	2007-04-18	Méthode d'obtention de dérivés peptidiques
AU657534B2 (en)	1995-03-16	Peptide process
EP0400065B1 (fr)	1997-08-27	Analogue de l'hormone de liberation de l'hormone de luteinisation (lhrh)
US5212288A (en)	1993-05-18	Temporary minimal protection synthesis of serine-containing polypeptides
NO844123L (no)	1985-04-18	Fremgangsmaate for fremstilling av nonapeptider og dodekopeptider
NO309428B1 (no)	2001-01-29	Fremgangsmåte for fast fase-syntese av en nona- og dekapeptid LH-RH analog
US7122628B2 (en)	2006-10-17	Process for the synthesis of a peptide having a Trp residue
RU2043362C1 (ru)	1995-09-10	Способ твердофазного синтеза пептидов
NO148373B (no)	1983-06-20	Fremgangsmaate ved fremstilling av et harpikspeptid
AU2002222439A1 (en)	2003-01-23	Process for the synthesis of a peptide having a tryptophan residue
EP0541662B1 (fr)	1994-11-02	Peptides de synthese antagonistes de la neurokinine a, leurs sels et leurs procedes de fabrication
Ohno et al.	1969	Synthesis of the fully protected, carboxyl-terminal tetradecapeptide sequence of staphylococcal nuclease
CA1335403C (fr)	1995-04-25	Procede et intermediaires pour les peptides lh-rh
IL97216A (en)	1995-10-31	Temporary minimal protection in solid phase synthesis of LH HR analogues
Bodanszky	1993	Solid Phase Peptide Synthesis
US20110046348A1 (en)	2011-02-24	Methods of preparing peptide derivatives