UA78058C2 - Pyrrolidine derivative as oxitocin antagonists - Google Patents

Pyrrolidine derivative as oxitocin antagonists Download PDF

Info

Publication number: UA78058C2
Authority: UA; Ukraine
Prior art keywords: group; biphenyl; pyrrolidin; formula; ylcarbonyl
Prior art date: 2002-07-05

Application number

UA20041210895A

Other languages

English (en)

Ukrainian (uk)

Original Assignee

Applied Research Systems

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.)

2002-07-05

Filing date

2003-04-07

Publication date

2007-02-15

2003-04-07 Application filed by Applied Research Systems filed Critical Applied Research Systems

2007-02-15 Publication of UA78058C2 publication Critical patent/UA78058C2/uk

Links

FKCMADOPPWWGNZ-YUMQZZPRSA-N [(2r)-1-[(2s)-2-amino-3-methylbutanoyl]pyrrolidin-2-yl]boronic acid Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1B(O)O FKCMADOPPWWGNZ-YUMQZZPRSA-N 0.000 title claims abstract description 26
239000005557 antagonist Substances 0.000 title description 6
239000000203 mixture Substances 0.000 claims abstract description 76
208000005107 Premature Birth Diseases 0.000 claims abstract description 22
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 21
206010036590 Premature baby Diseases 0.000 claims abstract description 18
206010013935 Dysmenorrhoea Diseases 0.000 claims abstract description 14
150000003839 salts Chemical class 0.000 claims abstract description 14
208000005171 Dysmenorrhea Diseases 0.000 claims abstract description 13
230000002265 prevention Effects 0.000 claims abstract description 7
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract description 4
150000001875 compounds Chemical class 0.000 claims description 154
-1 sulfonyloxy group Chemical group 0.000 claims description 56
101800000989 Oxytocin Proteins 0.000 claims description 50
XNOPRXBHLZRZKH-UHFFFAOYSA-N Oxytocin Natural products N1C(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CC(C)C)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C(C(C)CC)NC(=O)C1CC1=CC=C(O)C=C1 XNOPRXBHLZRZKH-UHFFFAOYSA-N 0.000 claims description 50
229960001723 oxytocin Drugs 0.000 claims description 50
XNOPRXBHLZRZKH-DSZYJQQASA-N oxytocin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@H](N)C(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 XNOPRXBHLZRZKH-DSZYJQQASA-N 0.000 claims description 45
125000003118 aryl group Chemical group 0.000 claims description 34
125000001072 heteroaryl group Chemical group 0.000 claims description 31
238000000034 method Methods 0.000 claims description 29
102000004279 Oxytocin receptors Human genes 0.000 claims description 23
108090000876 Oxytocin receptors Proteins 0.000 claims description 23
230000000694 effects Effects 0.000 claims description 23
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 19
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 15
210000003754 fetus Anatomy 0.000 claims description 15
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
239000008194 pharmaceutical composition Substances 0.000 claims description 15
QGKLPGKXAVVPOJ-UHFFFAOYSA-N pyrrolidin-3-one Chemical compound O=C1CCNC1 QGKLPGKXAVVPOJ-UHFFFAOYSA-N 0.000 claims description 15
102000005962 receptors Human genes 0.000 claims description 15
108020003175 receptors Proteins 0.000 claims description 15
208000035475 disorder Diseases 0.000 claims description 12
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
230000002028 premature Effects 0.000 claims description 11
239000001257 hydrogen Substances 0.000 claims description 10
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 9
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 8
150000001412 amines Chemical class 0.000 claims description 8
229910052757 nitrogen Inorganic materials 0.000 claims description 8
125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims description 7
125000002252 acyl group Chemical group 0.000 claims description 7
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 7
230000027455 binding Effects 0.000 claims description 6
125000000753 cycloalkyl group Chemical group 0.000 claims description 6
238000004519 manufacturing process Methods 0.000 claims description 6
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 6
229910052799 carbon Inorganic materials 0.000 claims description 5
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125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
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125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
238000010934 O-alkylation reaction Methods 0.000 claims description 3
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
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125000003277 amino group Chemical group 0.000 claims description 3
239000003638 chemical reducing agent Substances 0.000 claims description 3
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229910052760 oxygen Inorganic materials 0.000 claims description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
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125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
238000006268 reductive amination reaction Methods 0.000 claims 2
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125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 1
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102100031951 Oxytocin-neurophysin 1 Human genes 0.000 claims 1
150000001298 alcohols Chemical class 0.000 claims 1
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125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
238000012876 topography Methods 0.000 claims 1
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WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 21
239000012267 brine Substances 0.000 description 20
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
239000012074 organic phase Substances 0.000 description 19
230000015572 biosynthetic process Effects 0.000 description 17
150000003235 pyrrolidines Chemical class 0.000 description 17
229910052943 magnesium sulfate Inorganic materials 0.000 description 16
235000019341 magnesium sulphate Nutrition 0.000 description 16
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WEVYAHXRMPXWCK-UHFFFAOYSA-N methyl cyanide Natural products CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 11
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NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 10
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CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
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HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
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ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 7
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CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 7
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SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
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HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
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HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical class O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 6
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230000035945 sensitivity Effects 0.000 description 1
238000004904 shortening Methods 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
150000003385 sodium Chemical class 0.000 description 1
DVWOYOSIEJRHKW-UIRZNSHLSA-M sodium (2S)-2-[[(2S)-2-[[(4,4-difluorocyclohexyl)-phenylmethoxy]carbonylamino]-4-methylpentanoyl]amino]-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propane-1-sulfonate Chemical compound FC1(CCC(CC1)C(OC(=O)N[C@H](C(=O)N[C@H](C(S(=O)(=O)[O-])O)C[C@H]1C(NCC1)=O)CC(C)C)C1=CC=CC=C1)F.[Na+] DVWOYOSIEJRHKW-UIRZNSHLSA-M 0.000 description 1
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
239000004299 sodium benzoate Substances 0.000 description 1
235000010234 sodium benzoate Nutrition 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
235000009518 sodium iodide Nutrition 0.000 description 1
239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
239000011343 solid material Substances 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
230000008925 spontaneous activity Effects 0.000 description 1
230000006641 stabilisation Effects 0.000 description 1
238000011105 stabilization Methods 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000012089 stop solution Substances 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
229940124530 sulfonamide Drugs 0.000 description 1
150000003456 sulfonamides Chemical class 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
239000003826 tablet Substances 0.000 description 1
230000006794 tachycardia Effects 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
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
229960000195 terbutaline Drugs 0.000 description 1
BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
150000003555 thioacetals Chemical class 0.000 description 1
229940125712 tocolytic agent Drugs 0.000 description 1
239000003675 tocolytic agent Substances 0.000 description 1
230000003195 tocolytic effect Effects 0.000 description 1
210000003437 trachea Anatomy 0.000 description 1
BJBUEDPLEOHJGE-IMJSIDKUSA-N trans-3-hydroxy-L-proline Chemical compound O[C@H]1CC[NH2+][C@@H]1C([O-])=O BJBUEDPLEOHJGE-IMJSIDKUSA-N 0.000 description 1
125000004953 trihalomethyl group Chemical group 0.000 description 1
239000001226 triphosphate Substances 0.000 description 1
235000011178 triphosphate Nutrition 0.000 description 1
UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
229960000281 trometamol Drugs 0.000 description 1
230000001228 trophic effect Effects 0.000 description 1
230000002227 vasoactive effect Effects 0.000 description 1
229960003726 vasopressin Drugs 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
230000035899 viability Effects 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
238000012800 visualization Methods 0.000 description 1
239000000230 xanthan gum Substances 0.000 description 1
229920001285 xanthan gum Polymers 0.000 description 1
235000010493 xanthan gum Nutrition 0.000 description 1
229940082509 xanthan gum Drugs 0.000 description 1
125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- 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
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/06—Antiabortive agents; Labour repressants
- 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
- A61P5/10—Drugs for disorders of the endocrine system of the posterior pituitary hormones, e.g. oxytocin, ADH
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- 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
- C07D403/02—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 two hetero rings
- C07D403/06—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 two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Endocrinology (AREA)
Reproductive Health (AREA)
Diabetes (AREA)
Gynecology & Obstetrics (AREA)
Pregnancy & Childbirth (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Pyrrole Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

UA20041210895A 2002-07-05 2003-04-07 Pyrrolidine derivative as oxitocin antagonists UA78058C2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP02100784		2002-07-05
PCT/EP2003/050286 WO2004005249A1 (en)	2002-07-05	2003-07-04	Pyrrolidine derivatives as oxytocin antagonists

Publications (1)

Publication Number	Publication Date
UA78058C2 true UA78058C2 (en)	2007-02-15

Family

ID=30011225

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
UA20041210895A UA78058C2 (en)	2002-07-05	2003-04-07	Pyrrolidine derivative as oxitocin antagonists

Country Status (19)

Country	Link
US (1)	US7115754B2 (de)
EP (1)	EP1532109B1 (de)
JP (1)	JP4851085B2 (de)
CN (1)	CN1330633C (de)
AT (1)	ATE442354T1 (de)
BR (1)	BR0312586A (de)
CA (1)	CA2487532C (de)
DE (1)	DE60329189D1 (de)
EA (1)	EA008479B1 (de)
ES (1)	ES2330841T3 (de)
HR (1)	HRP20041208A2 (de)
IL (1)	IL166103A0 (de)
MX (1)	MXPA05000326A (de)
NO (1)	NO20050612L (de)
PL (1)	PL374666A1 (de)
RS (1)	RS115804A (de)
UA (1)	UA78058C2 (de)
WO (1)	WO2004005249A1 (de)
ZA (1)	ZA200409820B (de)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
RU2380110C1 (ru) *	2008-06-16	2010-01-27	Институт прикладной механики Уральского отделения Российской Академии Наук	Способ стимуляции родов по н.а. михайловой

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
KR20040030678A (ko) *	2001-06-18	2004-04-09	어플라이드 리서치 시스템스 에이알에스 홀딩 엔.브이.	피롤리딘 옥사디아졸 및 티아디아졸 유도체
US10722645B2 (en)	2011-12-21	2020-07-28	Deka Products Limited Partnership	Syringe pump, and related method and system
EP2845850A1 (de) *	2013-09-10	2015-03-11	ObsEva S.A.	Pyrrolidinderivate als Oxytocin/Vasopressin-V1a-Rezeptorantagonisten
EP2886107A1 (de)	2013-12-17	2015-06-24	ObsEva S.A.	Orale Formulierungen von Pyrrolydinderivaten
EP3753921A1 (de) *	2014-07-02	2020-12-23	ObsEva S.A.	Kristallines (3z,5s)-5-(hydroxymethyl)-1-[(2'-methyl-1,1'-biphenyl-4-yl)carbonyl]pyrrolidin-3-on-o-methyloxim und verfahren zur verwendung davon
EP3037101B1 (de) *	2014-12-22	2019-03-06	Ferring B.V.	Oxytocinrezeptorantagonistentherapie in der Lutealphase für Implantation und Schwangerschaft bei mit Technologien zur unterstützten Fortpflanzung behandelten Frauen
CA3009576A1 (en)	2016-01-04	2017-07-13	Merck Serono S.A.	L-valinate of hydroxypropylthiazolidine carboxamide derivative and salt form, crystal polymorph thereof
UA127283C2 (uk)	2016-07-21	2023-07-12	Обсева С.А.	Спосіб застосування антагоніста окситоцину для сприяння імплантації ембріона і запобігання викидню
US20220323410A1 (en)	2019-09-03	2022-10-13	ObsEva S.A.	Oxytocin antagonist dosing regimens for promoting embryo implantation and preventing miscarriage
WO2021160597A1 (en)	2020-02-10	2021-08-19	ObsEva S.A.	Biomarkers for oxytocin receptor antagonist therapy
TW202435864A (zh)	2023-02-09	2024-09-16	大陸商上海葆正醫藥科技有限公司	亞胺化合物及其製備方法和應用

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6329418B1 (en) *	1998-04-14	2001-12-11	The Procter & Gamble Company	Substituted pyrrolidine hydroxamate metalloprotease inhibitors
DK1268419T3 (da) *	2000-03-27	2006-10-02	Applied Research Systems	Farmaceutisk aktive pyrrolidinderivater som BAX-inhibitorer

2003
- 2003-04-07 UA UA20041210895A patent/UA78058C2/uk unknown
- 2003-07-04 EP EP03762692A patent/EP1532109B1/de not_active Expired - Lifetime
- 2003-07-04 MX MXPA05000326A patent/MXPA05000326A/es active IP Right Grant
- 2003-07-04 JP JP2004518783A patent/JP4851085B2/ja not_active Expired - Fee Related
- 2003-07-04 CA CA2487532A patent/CA2487532C/en not_active Expired - Fee Related
- 2003-07-04 CN CNB038204010A patent/CN1330633C/zh not_active Expired - Fee Related
- 2003-07-04 WO PCT/EP2003/050286 patent/WO2004005249A1/en not_active Ceased
- 2003-07-04 RS YUP-1158/04A patent/RS115804A/sr unknown
- 2003-07-04 DE DE60329189T patent/DE60329189D1/de not_active Expired - Lifetime
- 2003-07-04 PL PL03374666A patent/PL374666A1/xx not_active Application Discontinuation
- 2003-07-04 HR HR20041208A patent/HRP20041208A2/xx not_active Application Discontinuation
- 2003-07-04 BR BR0312586-6A patent/BR0312586A/pt not_active IP Right Cessation
- 2003-07-04 AT AT03762692T patent/ATE442354T1/de not_active IP Right Cessation
- 2003-07-04 US US10/518,543 patent/US7115754B2/en not_active Expired - Lifetime
- 2003-07-04 ES ES03762692T patent/ES2330841T3/es not_active Expired - Lifetime
- 2003-07-04 EA EA200500133A patent/EA008479B1/ru not_active IP Right Cessation
2004
- 2004-12-03 ZA ZA200409820A patent/ZA200409820B/en unknown
2005
- 2005-01-03 IL IL16610305A patent/IL166103A0/xx unknown
- 2005-02-03 NO NO20050612A patent/NO20050612L/no not_active Application Discontinuation

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
RU2380110C1 (ru) *	2008-06-16	2010-01-27	Институт прикладной механики Уральского отделения Российской Академии Наук	Способ стимуляции родов по н.а. михайловой

Also Published As

Publication number	Publication date
JP4851085B2 (ja)	2012-01-11
CN1678576A (zh)	2005-10-05
ES2330841T3 (es)	2009-12-16
PL374666A1 (en)	2005-10-31
ATE442354T1 (de)	2009-09-15
IL166103A0 (en)	2006-01-15
NO20050612L (no)	2005-02-03
CN1330633C (zh)	2007-08-08
EP1532109B1 (de)	2009-09-09
ZA200409820B (en)	2006-07-26
CA2487532A1 (en)	2004-01-15
CA2487532C (en)	2011-03-08
RS115804A (sr)	2007-02-05
US7115754B2 (en)	2006-10-03
MXPA05000326A (es)	2005-03-31
HRP20041208A2 (en)	2005-06-30
WO2004005249A1 (en)	2004-01-15
EA200500133A1 (ru)	2005-08-25
JP2005533828A (ja)	2005-11-10
DE60329189D1 (de)	2009-10-22
HK1076107A1 (en)	2006-01-06
BR0312586A (pt)	2005-04-12
US20060004020A1 (en)	2006-01-05
AU2003254498A1 (en)	2004-01-23
EP1532109A1 (de)	2005-05-25
EA008479B1 (ru)	2007-06-29

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ES2360882T3 (es)	2011-06-10	Derivados de tiazolidina carboxamida como moduladores del receptor de prostaglandina f.
EP1592389B1 (de)	2009-04-22	Derivate von piperazine-2-carboxamide
UA78058C2 (en)	2007-02-15	Pyrrolidine derivative as oxitocin antagonists
NO323969B1 (no)	2007-07-23	Farmasoytisk aktive pyrrolidinderivater
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TW200524578A (en)	2005-08-01	Protease inhibitors
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US9463187B2 (en)	2016-10-11	Methylphenidate derivatives and uses of them
US7189754B2 (en)	2007-03-13	Pyrrolidine ester derivatives with oxytocin modulating activity
CN106458859A (zh)	2017-02-22	作为治疗性化合物的新型ep4激动剂
JP4773335B2 (ja)	2011-09-14	オキシトシンアンタゴニストとしてのピロリジン誘導体
WO2023107481A1 (en)	2023-06-15	Amide-containing lonp1 inhibitor compounds, uses and methods
JP2020525401A (ja)	2020-08-27	デゾシン類似体塩酸塩の結晶形及び非晶質
AU2003254498B2 (en)	2009-02-12	Pyrrolidine derivatives as oxytocin antagonists
WO2025228411A1 (zh)	2025-11-06	一类单胺递质再摄取抑制剂化合物及其制备方法和应用
KR20050023390A (ko)	2005-03-09	옥시토신 길항제로서의 피롤리딘 유도체
KR20150090769A (ko)	2015-08-06	아릴옥시 아제티딘 화합물, 및 이를 포함하는 약학 조성물
HK1076107B (en)	2007-12-07	Pyrrolidine derivatives as oxytocin antagonists
BR112017026223B1 (pt)	2023-07-11	Moduladores de ror gama (rory)
NZ731847A (en)	2021-11-26	Heterocyclic derivatives and use thereof
NZ731847B2 (en)	2022-03-01	Heterocyclic derivatives and use thereof
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UA78058C2 - Pyrrolidine derivative as oxitocin antagonists - Google Patents

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Classifications

Landscapes

Applications Claiming Priority (2)

Publications (1)

Family

ID=30011225

Family Applications (1)

Country Status (19)

Cited By (1)

Families Citing this family (11)

Family Cites Families (2)

Cited By (1)

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