SI20026B - Heptapeptidni analogi - antagonisti oksitocina - Google Patents

Heptapeptidni analogi - antagonisti oksitocina Download PDF

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SI20026B
SI20026B SI9720076A SI9720076A SI20026B SI 20026 B SI20026 B SI 20026B SI 9720076 A SI9720076 A SI 9720076A SI 9720076 A SI9720076 A SI 9720076A SI 20026 B SI20026 B SI 20026B
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abu
asn
ile
mpa
ch2oh
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SI9720076A
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SI20026A (sl
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Per Melin
Anders Nilsson
Jerzy Trojnar
Carl-Johan Aurell
Pierre Riviere
Robert Haigh
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Ferring B.V.
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    • C07K7/04Linear peptides containing only normal peptide links
    • C07K7/16Oxytocins; Vasopressins; Related peptides
    • AHUMAN NECESSITIES
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    • A61P15/06Antiabortive agents; Labour repressants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00Drugs for genital or sexual disorders; Contraceptives
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    • A61P15/00Drugs for genital or sexual disorders; Contraceptives
    • A61P15/14Drugs for genital or sexual disorders; Contraceptives for lactation disorders, e.g. galactorrhoea
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    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02Muscle relaxants, e.g. for tetanus or cramps
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/18Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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    • A61P35/00Antineoplastic agents
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    • C07KPEPTIDES
    • C07K7/00Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/02Linear peptides containing at least one abnormal peptide link
    • AHUMAN NECESSITIES
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    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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Claims (18)

  1. -Ί- Heptapeptidni analogi - antagonisti oksitocina PATENTNI ZAHTEVKI 1. Heptapeptidni analog ali njegova farmacevtsko sprejemljiva sol, ki ima oksitocin antagonistično učinkovitost ter obstaja iz heksapeptidnega dela S in C-terininalnega β-aminoalkoholnega ostanka Z, vezanega na del S z amidno vezjo, pri čemer je β-aminoalkohol Z: -NR-CH-CHjOH (Z) Q v kateri Q stoji za -(CH2)n-NH-A, n je 1-6 in A je H ali -C(=NH)NH2> in kjer R stoji za CH3 ali C 2¾ in del S je: Mpa-X-Ile-Y-Asn-Abu- (S) l_I kjer imajo Mpa, Ile, Asn in Abu naslednje pomene: Mpa ostanek 3-merkaptopropionske kisline lle ostanek izolevcina Asn ostanek asparagina Abu ostanek α-aminomaslene kisline; in kjer je D-aromatska α-aminokislina; in je alifatska a-aminokislina. X Y -2-
  2. 2. Heptapeptidni analog po zahtevku 1, značilen po tem, daje X amino acilni ostanek D-triptofana ali p-(2-naftil)-D-alanina.
  3. 3. Heptapeptidni analog po zahtevku 2, značilen po tem, da je Y amino acilni ostanek levcina, valina, izolevcina, aloizolevcina, β,β-dietilalanina, cikloheksilalanina ali cikloheksilglicina.
  4. 4. Heptapeptidni analog po zahtevku 1, značilen po tem, daje Y amino acilni ostanek levcina, valina, izolevcina, aloizolevcina, β,β-dietilalanina, cikloheksilalanina ali cikloheksilglicina.
  5. 5. Heptapeptidni analog po zahtevku 4, značilen po tem, daje n enak 2, 3 ali 4.
  6. 6. Heplapeptidni analog po zahtevku 1, značilen po tem, daje n enak 2, 3 ali 4.
  7. 7. Heptapeptidni analog po zahtevku 6, značilen po tem, da je X amino acilni ostanek D-triptofana ali β-(2-naftil)-D-alanina.
  8. 8. Heptapeptidni analog po zahtevku 1, značilen po tem, daje X amino acilni ostanek D-triptofana ali β-(2-η3ίΐί1)-0-3ΐ3ηϊηη, Y je amino acilni ostanek levcina, valina, izolevcina, aloizolevcina, β,β-dietilalanina, cikloheksilalanina ali cikloheksilglicina, in n stoji za 2, 3 ali 4.
  9. 9. Heptapeptidni analog po zahtevku 8, značilen po tem, daje izbran izmed: M^a-D-Trp-Ile-aloi le-Asn-Abu-N-CH-CH2OH CH3 CH2CH2CH2NH2 Mpa-D-Trp-Ile-aloIle-Asn-Abu-N-CH-CH2OH CHj CHzCHzCHjCHjNHz - 3~ Mjja-D-Trp-Ile-aloIle-Asn-Abu-N-CH-CH2OH CHj CH2CH2NH2 Hpa-D-Trp-Ile- alolle -Asn-Abu-N-CH-CH2OH 1-1 | | CHj ch2ch2ch2nh-c=nh I nh2 Mpa-D-Trp-Ile-Ala (3, 3-dietll . )-Asn-Abu-N-CH-CH2OH *--1 I I ch3 ch2ch2ch2nh2 Mpa-D-Nal-Ile- alolle -Asn-Abu-N-CH-CH2OH CHj CH2CH2CH2NH2 Mpa-D-Nal-Ile-Ala (3, 3- dietil ) -Asn-Abu-N-CH-CH2OH I-1 I I CH3 CH2CH2CH2NH2 J I I ch3 ch2ch2ch2nh2 M^a-D-Trp-Ile-Ile-Asn-Abu-N-CH-CH2OH Mpa-D-Trp-I le-Leu-Asn-Abu-N-CH-CH2OH l___I I CHj CH2CH2CH2NH2 J Mpa-D-Trp-I1e-Val-Asn-Abu-N-CH-CH2OH CH, CH2CH2CH2NH2 Mpa-D-Trp-Ile-Cha-Asn-Abu-N-CH-CH2OH CHj CH2CH2CH2NH2
  10. 10. Heptapeptidni analog po zahtevku 1, značilen po tem, da ima strukturo: M l a-D-Trp-Ile- alolle -Asn-Abu-N CH-CH2OH CHj CH2CH2CH2NHz -4-
  11. 11. Heptapeptidni analog po zahtevku 1, značilen po tem, da ima strukturo: Mpa-D-Trp-Ile-· alolle -Asn-Abu-N CH CH2OH Ϊ-1-1 I I CH, ch,ch2ch,ch,nh,
  12. 12. Heptapeptidni analog po zahtevku 1, značilen po tem, da ima strukturo: Mpa-D-Trp-Ile- alolle -Asn-Abu-N-CH-CH2OH Ϊ-1 | I CH3 CH2CH2CH2NH-C=NH I nh2
  13. 13. Heptapeptidni analog po zahtevku 1, značilen po tem, da ima strukturo: Mpa-D-Nal-Ile-Ala (3, 3- dietil ) -Asn-Abu-N-CH-CH2OH -1 | | CH3 CH2CH2CH2NH2
  14. 14. Heptapeptidni analog po zahtevku 1, značilen po tem, da ima strukturo: Mpa-D-Nal-Ile- alolle -Asn-Abu-N-CH-CH2OH CH3 CH2CH2CH2NH2
  15. 15. Farmacevtski sestavek, značilen po tem, da obsega farmakološko učinkovito množino heptapeptidnega analoga po zahtevku 1, in farmacevtsko sprejemljiv nosilec.
  16. 16. Sestavek po zahtevku 15, značilen po tem, daje vodna raztopina za nazalno, subkutano ali intravenozno dajanje.
  17. 17. Sestavek po zahtevku 15, značilen po tem, da nosilec vključuje pufrsko sredstvo.
  18. 18. Sestavek po zahtevku 15, značilen po tem, da je v obliki tablete, kapsule, granul in podobnega, za oralno dajanje. Ί9· Postopek za pripravo heptapeptidnega analoga ali njegove farmacevtsko sprejemljive soli, ki imajo oksitocin-antagonistično učinkovitost in obstajajo iz heksapeplidnega dela S in C-terminalnega β-aminoalkoholnega ostanka Z, vezanega na del S z amidno vezjo, pri čemer je β-aminoalkohol Z: (Z) -NR-CH-CHjOH I Q v kateri Q stoji za -(CP^n-NH-A, n je 1-6 in A je H ali -C(=NH)NH2, in kjer R stoji za CHj ali C2H5; in del S je: (S) Mpa-X-Ile-Y-Asn-Abu-I_I kjer imajo Mpa, Ilc, Asn in Abu naslednje pomene: Mpa ostanek 3-merkaptopropionske kisline Ile ostanek izolevcina Asn ostanek asparagina Abu ostanek α-aminomaslcne kisline; in kjer X je D-aromatska α-aminokislina; in Y je alifatska a-aminokislina. z redukcijo ustrezne spojine, v kateri L stoji za Y: -NR1-CH-CO-OBn (Y) H -6- v kateri M stoji za (CH2)n-N(Pht) ali -(CH2)n-N(P)-C(=NP)NP2, dve izmed skupin P zaščitna skupina za dušik, ostale pa so vodik, n je CH3 ali C2H5, z uporabo borohidridne soli ali substiluiranega boroliidrida ali borana. 20. Postopek po zahtevku 19» značilen po tem, daje borohidrid NaBILt.
    v kateri je ena ali l-6, R1 pa stoji za
SI9720076A 1996-11-26 1997-11-21 Heptapeptidni analogi - antagonisti oksitocina SI20026B (sl)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE9604341A SE9604341D0 (sv) 1996-11-26 1996-11-26 Hepta-peptide oxytocin analogue
PCT/SE1997/001968 WO1998023636A1 (en) 1996-11-26 1997-11-21 Heptapeptide oxytocin analogues

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SI20026A SI20026A (sl) 2000-02-29
SI20026B true SI20026B (sl) 2000-06-30

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EP (1) EP0938496B1 (sl)
JP (1) JP3405460B2 (sl)
KR (1) KR100463132B1 (sl)
CN (1) CN1129606C (sl)
AR (1) AR008531A1 (sl)
AT (1) ATE242264T1 (sl)
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BR (1) BR9713366B1 (sl)
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CZ (1) CZ299532B6 (sl)
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SE (1) SE9604341D0 (sl)
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TR (1) TR199901028T2 (sl)
UA (1) UA54459C2 (sl)
WO (1) WO1998023636A1 (sl)
ZA (1) ZA9710518B (sl)

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SE528446C2 (sv) * 2006-03-02 2006-11-14 Ferring Int Ct Sa Farmaceutisk sammansättning innefattande desmopressin, kiseldioxid och stärkelse
KR101522747B1 (ko) 2007-08-06 2015-05-26 알레간 인코포레이티드 데스모프레신 약물 전달을 위한 방법 및 장치
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CN102875650B (zh) * 2012-09-26 2014-06-11 深圳翰宇药业股份有限公司 巴卢西班的制备方法
US9365615B2 (en) 2013-09-09 2016-06-14 Jitsubo Co., Ltd. Cross-linked peptides containing non-peptide cross-linked structure, method for synthesizing cross-linked peptides, and novel organic compound used in method
EP3037101B1 (en) 2014-12-22 2019-03-06 Ferring B.V. Oxytocin receptor antagonist therapy in the luteal phase for implantation and pregnancy in women undergoing assisted reproductive technologies
US9750785B2 (en) 2015-01-30 2017-09-05 Par Pharmaceutical, Inc. Vasopressin formulations for use in treatment of hypotension
US9744209B2 (en) 2015-01-30 2017-08-29 Par Pharmaceutical, Inc. Vasopressin formulations for use in treatment of hypotension
US9687526B2 (en) 2015-01-30 2017-06-27 Par Pharmaceutical, Inc. Vasopressin formulations for use in treatment of hypotension
US9937223B2 (en) 2015-01-30 2018-04-10 Par Pharmaceutical, Inc. Vasopressin formulations for use in treatment of hypotension
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EP3359557A1 (en) 2015-10-06 2018-08-15 Ferring B.V. New methods for making barusiban and its intermediates
RS63286B1 (sr) 2016-01-04 2022-06-30 ObsEva SA Istovremeno davanje alfa-amino estra hidroksipropiltiazolidin karboksamidnog derivata i tokolitičkog agensa
MX2019000498A (es) 2016-07-21 2019-09-16 ObsEva SA Regímenes de dosis de antagonista de oxitocina para promover la implantación embrionaria y prevenir abortos espontaneos.
WO2021043726A1 (en) 2019-09-03 2021-03-11 ObsEva S.A. Oxytocin antagonist dosing regimens for promoting embryo implantation and preventing miscarriage
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NO992532D0 (no) 1999-05-26
LT4650B (lt) 2000-04-25
NO321380B1 (no) 2006-05-02
ZA9710518B (en) 1998-06-10
CZ183299A3 (cs) 2000-05-17
RO120772B1 (ro) 2006-07-28
ATE242264T1 (de) 2003-06-15
CZ299532B6 (cs) 2008-08-27
PT938496E (pt) 2003-10-31
AU5142998A (en) 1998-06-22
HU228568B1 (en) 2013-04-29
HUP0000577A3 (en) 2001-02-28
SK283800B6 (sk) 2004-02-03
BR9713366B1 (pt) 2010-05-18
CN1129606C (zh) 2003-12-03
HK1022481A1 (en) 2000-08-11
CN1238781A (zh) 1999-12-15
IL129519A0 (en) 2000-02-29
RU2180668C2 (ru) 2002-03-20
JP2000507617A (ja) 2000-06-20
DE69722651T2 (de) 2004-04-08
SI20026A (sl) 2000-02-29
EP0938496B1 (en) 2003-06-04
KR100463132B1 (ko) 2004-12-23
LV12350A (lv) 1999-09-20
NZ336445A (en) 2000-06-23
KR20000069045A (ko) 2000-11-25
EE9900210A (et) 1999-12-15
CA2272990A1 (en) 1998-06-04
AU713424B2 (en) 1999-12-02
ES2203823T3 (es) 2004-04-16
DE69722651D1 (en) 2003-07-10
PL189292B1 (pl) 2005-07-29
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HUP0000577A2 (hu) 2000-11-28
DK0938496T3 (da) 2003-10-06
LV12350B (en) 1999-11-20
BR9713366A (pt) 2000-01-25
LT99052A (en) 2000-01-25
IL129519A (en) 2004-09-27
SE9604341D0 (sv) 1996-11-26
NO992532L (no) 1999-05-26
HRP970630A2 (en) 1998-10-31
UA54459C2 (uk) 2003-03-17
EP0938496A1 (en) 1999-09-01
SK70499A3 (en) 2000-10-09
AR008531A1 (es) 2000-01-19
TR199901028T2 (xx) 1999-07-21
JP3405460B2 (ja) 2003-05-12
HRP970630B1 (en) 2002-04-30
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EE03832B1 (et) 2002-08-15

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