HRP20191679T1 - Derivati pirazolopirimidona ili pirolotriazona, postupak pripreme jednakih i njihove farmaceutske uporabe - Google Patents
Derivati pirazolopirimidona ili pirolotriazona, postupak pripreme jednakih i njihove farmaceutske uporabe Download PDFInfo
- Publication number
- HRP20191679T1 HRP20191679T1 HRP20191679T HRP20191679T1 HR P20191679 T1 HRP20191679 T1 HR P20191679T1 HR P20191679 T HRP20191679 T HR P20191679T HR P20191679 T1 HRP20191679 T1 HR P20191679T1
- Authority
- HR
- Croatia
- Prior art keywords
- compound
- formula
- pharmaceutically acceptable
- acceptable salt
- mixture
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims 4
- DOTPSQVYOBAWPQ-UHFFFAOYSA-N pyrazolo[4,3-d]pyrimidin-3-one Chemical compound N1=CN=C2C(=O)N=NC2=C1 DOTPSQVYOBAWPQ-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 32
- 150000003839 salts Chemical class 0.000 claims 20
- 239000000203 mixture Substances 0.000 claims 16
- 125000000217 alkyl group Chemical group 0.000 claims 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 8
- 229910052736 halogen Inorganic materials 0.000 claims 7
- 125000005843 halogen group Chemical group 0.000 claims 7
- 238000002360 preparation method Methods 0.000 claims 5
- 230000001419 dependent effect Effects 0.000 claims 4
- 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 3
- 206010028980 Neoplasm Diseases 0.000 claims 3
- 206010046798 Uterine leiomyoma Diseases 0.000 claims 3
- 239000003163 gonadal steroid hormone Substances 0.000 claims 3
- 201000010260 leiomyoma Diseases 0.000 claims 3
- 206010006187 Breast cancer Diseases 0.000 claims 2
- 208000026310 Breast neoplasm Diseases 0.000 claims 2
- 101100516563 Caenorhabditis elegans nhr-6 gene Proteins 0.000 claims 2
- 201000009273 Endometriosis Diseases 0.000 claims 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
- 206010060862 Prostate cancer Diseases 0.000 claims 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 2
- 208000002495 Uterine Neoplasms Diseases 0.000 claims 2
- 230000010933 acylation Effects 0.000 claims 2
- 238000005917 acylation reaction Methods 0.000 claims 2
- 125000003118 aryl group Chemical group 0.000 claims 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 2
- 238000006243 chemical reaction Methods 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 229940079593 drug Drugs 0.000 claims 2
- 125000001188 haloalkyl group Chemical group 0.000 claims 2
- 125000001072 heteroaryl group Chemical group 0.000 claims 2
- 229910052739 hydrogen Inorganic materials 0.000 claims 2
- 239000001257 hydrogen Substances 0.000 claims 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims 2
- 230000002265 prevention Effects 0.000 claims 2
- 206010046766 uterine cancer Diseases 0.000 claims 2
- 201000007954 uterine fibroid Diseases 0.000 claims 2
- 208000002874 Acne Vulgaris Diseases 0.000 claims 1
- 201000004384 Alopecia Diseases 0.000 claims 1
- 208000024827 Alzheimer disease Diseases 0.000 claims 1
- 201000000736 Amenorrhea Diseases 0.000 claims 1
- 206010001928 Amenorrhoea Diseases 0.000 claims 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims 1
- 101000904177 Clupea pallasii Gonadoliberin-1 Proteins 0.000 claims 1
- 208000005171 Dysmenorrhea Diseases 0.000 claims 1
- 206010013935 Dysmenorrhoea Diseases 0.000 claims 1
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 claims 1
- 206010027452 Metastases to bone Diseases 0.000 claims 1
- 208000007913 Pituitary Neoplasms Diseases 0.000 claims 1
- 206010036618 Premenstrual syndrome Diseases 0.000 claims 1
- 208000004403 Prostatic Hyperplasia Diseases 0.000 claims 1
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 claims 1
- 206010000496 acne Diseases 0.000 claims 1
- 231100000360 alopecia Toxicity 0.000 claims 1
- 231100000540 amenorrhea Toxicity 0.000 claims 1
- 150000001412 amines Chemical class 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 239000003153 chemical reaction reagent Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 238000011010 flushing procedure Methods 0.000 claims 1
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound 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 claims 1
- 238000005658 halogenation reaction Methods 0.000 claims 1
- 239000005556 hormone Substances 0.000 claims 1
- 229940088597 hormone Drugs 0.000 claims 1
- 239000000411 inducer Substances 0.000 claims 1
- 208000000509 infertility Diseases 0.000 claims 1
- 230000036512 infertility Effects 0.000 claims 1
- 208000021267 infertility disease Diseases 0.000 claims 1
- 208000002551 irritable bowel syndrome Diseases 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 239000003539 oral contraceptive agent Substances 0.000 claims 1
- 210000001672 ovary Anatomy 0.000 claims 1
- 230000016087 ovulation Effects 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 201000002511 pituitary cancer Diseases 0.000 claims 1
- 201000010065 polycystic ovary syndrome Diseases 0.000 claims 1
- 230000002980 postoperative effect Effects 0.000 claims 1
- 208000006155 precocious puberty Diseases 0.000 claims 1
- 125000002098 pyridazinyl group Chemical group 0.000 claims 1
- 230000001850 reproductive effect Effects 0.000 claims 1
- 238000007363 ring formation reaction Methods 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
- 208000011580 syndromic disease Diseases 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- 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
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- 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
- A61P15/18—Feminine contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/10—Anti-acne agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
-
- 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
- A61P5/02—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
- A61P5/04—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin for decreasing, blocking or antagonising the activity of the hypothalamic hormones
-
- 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
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
-
- 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
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/32—Antioestrogens
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Diabetes (AREA)
- Neurosurgery (AREA)
- Dermatology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Gynecology & Obstetrics (AREA)
- Urology & Nephrology (AREA)
- Pregnancy & Childbirth (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Claims (18)
1. Spoj formule (I), ili tautomer, mezomer, racemat, enantiomer, dijastereomer ili njihova smjesa, ili njegova farmaceutski prihvatljiva sol:
pri čemu:
kada G je N, D je C i E je -CH-;
kada G je C, D i E su N;
R1 je odabran iz skupine koju čine 6-člani aril i 6-člani heteroaril, pri čemu su aril i heteroaril svaki neovisno opcijski nadalje supstituirani s jednom ili više skupina odabrani iz skupine koju čine halogen i -OR6;
R2 je C1-6alkil, gdje je alkil dalje supstituiran s fenilom, pri čemu je fenil opcijski nadalje supstituiran s jednom ili više skupina odabranih iz skupine koju čine halogen, alkil i haloalkil;
R3 je fenil, pri čemu je svaki fenil opcijski nadalje supstituiran s jednom ili više skupina odabranih iz skupine koju čine -NHC(O)R6, -NHC(O)OR6, -NHC(O)NHR6 i -NHC(O)NHOR6;
R4 je C1-6 alkil;
R5 je vodik;
R6 je odabran iz skupine koju čine vodik i alkil;
n je 1 ili 2.
2. Spoj formule (I) sukladno patentnom zahtjevu 1, ili tautomer, mezomer, racemat, enantiomer, dijastereomer ili njihova smjesa, ili njegova farmaceutski prihvatljiva sol, koja je spoj formule (II) ili tautomer, mezomer, racemat, enantiomer, dijastereomer ili njihova smjesa ili njegova farmaceutski prihvatljiva sol:
gdje: n i R1 do R5 su kao što je utvrđeno u patentnom zahtjevu 1.
3. Spoj formule (I) sukladno patentnom zahtjevu 1, ili tautomer, mezomer, racemat, enantiomer, dijastereomer ili njihova smjesa, ili njegova farmaceutski prihvatljiva sol, koja je spoj formule (III) ili tautomer, mezomer, racemat, enantiomer, dijastereomer ili njihova smjesa ili njegova farmaceutski prihvatljiva sol:
gdje: n i R1 do R5 su kao što je utvrđeno u patentnom zahtjevu 1.
4. Spoj formule (I) sukladno bilo kojem od patentnom zahtjeva 1 do 3, ili tautomer, mezomer, racemat, enantiomer, dijastereomer ili njihova smjesa, ili njegova farmaceutski prihvatljiva sol, pri čemu je R1 odabran iz skupine koju čine fenil i piridazinia, pri čemu su fenil i piridazinil svaki opcijski nadalje supstituirani s jednom ili više skupina odabranih iz skupine koju čine halogen i -OR6.
5. Spoj formule (I) sukladno bilo kojem od patentnom zahtjeva 1 do 4, ili tautomer, mezomer, racemat, enantiomer, dijastereomer ili njihova smjesa, ili njegova farmaceutski prihvatljiva sol, pri čemu je R2 benzil, pri čemu je benzil opcijski supstituiran s jednom ili više skupina odabranih iz skupine koju čine halogen, alkil i haloalkil.
6. Spoj formule (I) sukladno bilo kojem od patentnom zahtjeva 1 do 4, ili tautomer, mezomer, racemat, enantiomer, dijastereomer ili njihova smjesa, ili njegova farmaceutski prihvatljiva sol, gdje je R3 fenil, pri čemu je fenil opcijski dalje supstituiran s jednom ili više skupina odabranih iz skupine koju čine -NHC(O)NHR6 i -NHC(O)NHOR6.
7. Spoj formule (I) sukladno bilo kojem od patentnom zahtjeva 1 do 5, ili tautomer, mezomer, racemat, enantiomer, dijastereomer ili njihova smjesa, ili njegova farmaceutski prihvatljiva sol, gdje je R4 metil.
8. Spoj formule (I) sukladno patentnom zahtjevu 1, ili tautomer, mezomer, racemat, enantiomer, dijastereomer ili njihova smjesa, ili njegova farmaceutski prihvatljiva sol, koja je spoj formule (IV) ili tautomer, mezomer, racemat, enantiomer, dijastereomer ili njihova smjesa ili njegova farmaceutski prihvatljiva sol:
pri čemu: n, D, E, G, R1, R2, R4 i R5 su kao što je definirano u patentnom zahtjevu 1;
Ra je odabran iz skupine koju čine alkil i -OR6; i
R6 je alkil.
9. Spoj formule (I) sukladno bilo kojem od patentnom zahtjeva 1 do 7, ili tautomer, mezomer, racemat, enantiomer, dijastereomer ili njihova smeša, ili njegova farmaceutski prihvatljiva sol, gdje je spoj odabran iz skupine koju čine:
10. Postupak pripreme spoja formule (I) sukladno patentnom zahtjevu 1, ili tautomera, mezomera, racemata, enantiomera, dijastereomera ili njihove smjese, ili njegove farmaceutski prihvatljive soli, koji sadrži korak:
reakcije spoja formule (IA) sa aminom NH(R4) (CH2) nR5; opcijski redukcija ili / i acilacija dobivenog proizvoda da bi se dobio spoj formule (I);
gdje: X je halogen; n, D, E, G i R1 do R5 su kako je utvrđeno u patentnom zahtjevu 1.
11. Postupak pripreme spoja formule (I) sukladno patentnom zahtjevu 1, ili tautomera, mezomera, racemata, enantiomera, dijastereomera ili njihove smjese, ili njegove farmaceutski prihvatljive soli, koji sadrži korak:
reakcije spoja formule (IB) sa R2X u prisustvu alkalnog reagensa; opcijski redukcija ili / i acilacija dobivenog proizvoda da bi se dobio spoj formule (I);
gdje: X je halogen; n, D, E, G i R1 do R5 su kako je utvrđeno u patentnom zahtjevu 1.
12. Spoj formule (IA), ili njegova farmaceutski prihvatljiva sol, koja je korištena kao intermedijator u pripremi spoja formule (I):
gdje:
X je halogen;
D, E, G i Rl do R3 su kao što je utvrđeno u formuli (I).
13. Spoj formule (IB), ili njegova farmaceutski prihvatljiva sol, koja je upotrjebljena kao intermedijator u pripremi spoja formule (I):
pri čemu:
n, D, E, G, R1 i R3 do R5 su kao što je utvrđeno u formuli (I).
14. Postupak za pripremu spoja formule (IA) prema patentnom zahtjevu 12, ili njegove farmaceutski prihvatljive soli, koji sadrži korak:
provođenje reakcije halogeniranja spoja formule (Ib) da bi se dobio spoj formule (IA);
gdje su: D, E, G i Rl do R3 kao što je utvrđeno u patentnom zahtjevu 1.
15. Postupak pripreme spoja formule (IB) sukladno patentnom zahtjevu 13, ili njegove farmaceutski prihvatljive soli, koji obuhvaća korak:
sprovođenje ciklizacije spoja formule (Ig) da bi se dobio spoj formule (IB);
pri čemu: n, D, E, G, R1 i R3~R5 su kao što je utvrđeno u patentnom zahtjevu 1;
Rb je alkil.
16. Spoj odabran iz skupine koju čine:
17. Farmaceutski pripravak koji sadrži terapeutski učinkovitu količinu spoja formule (I) sukladno bilo kojem od patentnih zahtjeva 1 do 9, ili tautomera, mezomera, racemata, enantiomera, dijastereomera ili njihove smjese, ili njegovu farmaceutski prihvatljivu sol, i jedan ili više farmaceutski prihvatljivih nosača, otapala ili ekscipijensa.
18. Spoj formule (I) sukladno bilo kojem od patentnom zahtjeva 1 do 9, ili tautomer, mezomer, racemat, enantiomer, dijastereomer ili njihova smjesa, ili njegova farmaceutski prihvatljiva sol, ili farmaceutski preparat sukladno patentnom zahtjevu 17, za uporabu kao lijekova u liječenju ili prevenciju karcinoma ovisnih o spolnim hormonima koštanih metastaza od karcinoma ovisnih o spolnim hormonima, hiperplazije prostate, leiomioma maternice, endometrioze, fibroida maternice, preuranjenog puberteta, amenoreje, predmenstrualnog sindroma, dismenoreje, sindroma multilokularnog jajnika, sindroma policističnih jajnika, akni, alopecije, Alzheimerove bolest, steriliteta, sindroma iritabilnog crijeva, benignih ili malignih tumora koji nisu ovisni o hormonima i osjetljivi na LH-RH ili crvenila; za uporabu kao reproduktivni regulator, kontracepcijska pilula, evokator ovulacije; ili za uporabu kao lijekova za prevenciju postoperativnog recidiva karcinoma ovisnih o spolnim hormonima, odabranog iz skupine koju čine karcinom prostate, karcinom maternice, karcinom dojke i karcinom hipofize; po mogućnosti karcinom prostate, karcinom materice, karcinom dojke, endometrioze ili leiomioma maternice.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310525956 | 2013-10-30 | ||
| PCT/CN2014/087906 WO2015062391A1 (zh) | 2013-10-30 | 2014-09-30 | 吡唑并嘧啶酮类或吡咯并三嗪酮类衍生物、其制备方法及其在医药上的应用 |
| EP14858090.5A EP3064498B1 (en) | 2013-10-30 | 2014-09-30 | Pyrazolopyrimidone or pyrrolotriazone derivatives, method of preparing same, and pharmaceutical applications thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20191679T1 true HRP20191679T1 (hr) | 2019-12-13 |
Family
ID=53003302
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20191679 HRP20191679T1 (hr) | 2013-10-30 | 2019-09-17 | Derivati pirazolopirimidona ili pirolotriazona, postupak pripreme jednakih i njihove farmaceutske uporabe |
Country Status (21)
| Country | Link |
|---|---|
| US (3) | US10005781B2 (hr) |
| EP (1) | EP3064498B1 (hr) |
| JP (1) | JP6412563B2 (hr) |
| CN (1) | CN104884457B (hr) |
| AU (1) | AU2014344504C1 (hr) |
| BR (1) | BR112016008799B1 (hr) |
| CA (1) | CA2927641C (hr) |
| CY (1) | CY1122196T1 (hr) |
| DK (1) | DK3064498T3 (hr) |
| ES (1) | ES2747839T3 (hr) |
| HR (1) | HRP20191679T1 (hr) |
| HU (1) | HUE046314T2 (hr) |
| LT (1) | LT3064498T (hr) |
| MX (1) | MX2016005142A (hr) |
| PL (1) | PL3064498T3 (hr) |
| PT (1) | PT3064498T (hr) |
| RS (1) | RS59457B1 (hr) |
| RU (1) | RU2674977C2 (hr) |
| SI (1) | SI3064498T1 (hr) |
| TW (1) | TWI675838B (hr) |
| WO (1) | WO2015062391A1 (hr) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX2016005142A (es) * | 2013-10-30 | 2016-10-28 | Shanghai hengrui pharmaceutical co ltd | Derivados de pirazolopirimidona o pirrolotriazona, metodo y preparacion de los mismos y aplicaciones farmaceuticas de los mismos. |
| CN108778280B (zh) * | 2016-11-07 | 2021-07-27 | 江苏恒瑞医药股份有限公司 | 一种GnRH受体拮抗剂的多晶型及其制备方法 |
| HUE055891T2 (hu) * | 2016-11-14 | 2022-01-28 | Jiangsu Hengrui Medicine Co | A gonadotropint felszabadító hormon (GNRH) receptor antagonista kristályos formája és annak elõállítási módja |
| UA126345C2 (uk) * | 2017-07-28 | 2022-09-21 | Джянгсу Хенгруй Медісін Ко., Лтд. | Спосіб отримання похідної гетероарилпіримідону та гетероарилпіримідонової проміжної похідної сполуки |
| CN109970662B (zh) * | 2017-12-27 | 2023-06-30 | 上海科胜药物研发有限公司 | 一种制备噁拉戈利中间体的方法 |
| CN117203209A (zh) * | 2021-04-02 | 2023-12-08 | 江苏恒瑞医药股份有限公司 | 一种GnRH受体拮抗剂的结晶形式及其制备方法 |
| CN115260211B (zh) * | 2021-04-29 | 2024-02-06 | 长春金赛药业有限责任公司 | 含噻吩稠环类衍生物、药物组合物及其制备方法和应用 |
| CN117769424A (zh) * | 2021-08-30 | 2024-03-26 | 江苏恒瑞医药股份有限公司 | 一种GnRH受体拮抗剂的结晶工艺 |
| CN115141809B (zh) * | 2022-08-30 | 2023-05-02 | 南京诺唯赞生物科技股份有限公司 | 一种检测gnrh结合蛋白生物学活性的方法及试剂盒 |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5171835A (en) | 1988-10-21 | 1992-12-15 | The Administrators Of The Tulane Educational Fund | LHRH antagonists |
| US20020065309A1 (en) | 1999-08-04 | 2002-05-30 | Ge Peng | Novel Bicyclic and tricyclic pyrrolidine derivatives as GnRH antagonists |
| JP5072166B2 (ja) * | 2002-01-30 | 2012-11-14 | 武田薬品工業株式会社 | チエノピリミジン化合物、その製造法および用途 |
| US7569570B2 (en) * | 2002-01-30 | 2009-08-04 | Takeda Pharmaceutical Company Limited | Thienopyrimidines, process for preparing the same and use thereof |
| AU2003253165A1 (en) * | 2002-08-13 | 2004-02-25 | Warner-Lambert Company Llc | Pyrimidine fused bicyclic metalloproteinase inhibitors |
| JP4039574B2 (ja) * | 2003-01-29 | 2008-01-30 | 武田薬品工業株式会社 | チエノピリミジン化合物およびその用途 |
| SG156636A1 (en) * | 2004-10-12 | 2009-11-26 | Decode Genetics Ehf | Carboxylic acid peri -substituted bicyclics for occlusive artery disease |
| WO2006074051A2 (en) * | 2004-12-30 | 2006-07-13 | Diakine Therapeutics, Inc. | PHARMACEUTICAL COMPOSITIONS AND METHODS FOR RESTORING β-CELL MASS AND FUNCTION |
| WO2006083005A1 (ja) * | 2005-02-03 | 2006-08-10 | Takeda Pharmaceutical Company Limited | 縮合ピリミジン誘導体およびその用途 |
| US20060211699A1 (en) | 2005-03-07 | 2006-09-21 | Wyeth | Quinoxaline dihydrohalide dihydrates and synthetic methods therefor |
| CN101468988A (zh) * | 2007-12-26 | 2009-07-01 | 上海恒瑞医药有限公司 | 哌嗪类衍生物,其制备方法及其在医药上的应用 |
| EP2329823A4 (en) | 2008-09-03 | 2013-04-03 | Takeda Pharmaceutical | METHOD FOR IMPROVING CAPACITY OF PREPARATION TO BE ABSORBED AND PREPARATION WHICH CAPACITY TO BE ABSORBED IS IMPROVED |
| ES2456515T3 (es) * | 2009-03-23 | 2014-04-22 | Glenmark Pharmaceuticals S.A. | Derivados de pirimidindiona fusionados como moduladores de TRPA1 |
| TW201130854A (en) | 2009-12-22 | 2011-09-16 | Bayer Schering Pharma Ag | Pyridinone derivatives and pharmaceutical compositions thereof |
| US9227971B2 (en) | 2010-01-19 | 2016-01-05 | Merck Sharp & Dohme Corp. | Pyrazolo[1,5-a]pyrimidine compounds as mTOR inhibitors |
| CN102807568B (zh) | 2011-05-31 | 2015-11-25 | 正大天晴药业集团股份有限公司 | 噻二唑衍生物类dpp-iv抑制剂 |
| WO2012175514A1 (en) | 2011-06-21 | 2012-12-27 | Bayer Intellectual Property Gmbh | Pyridinone derivatives and pharmaceutical compositions thereof |
| SI2776038T1 (en) * | 2011-11-11 | 2018-06-29 | Gilead Apollo, Llc | ACC INHIBITORS AND THEIR USE |
| JP6209171B2 (ja) | 2012-02-28 | 2017-10-04 | ティウムバイオ カンパニー、リミテッドＴｉｕｍＢｉｏ Ｃｏ．， Ｌｔｄ． | ゴナドトロピン放出ホルモン受容体アンタゴニスト、その製造方法および該アンタゴニストを含む医薬組成物 |
| CN102807569B (zh) * | 2012-08-21 | 2015-02-25 | 四川大学 | 一种镇静催眠的化合物及其制备方法和用途 |
| MX2016005142A (es) * | 2013-10-30 | 2016-10-28 | Shanghai hengrui pharmaceutical co ltd | Derivados de pirazolopirimidona o pirrolotriazona, metodo y preparacion de los mismos y aplicaciones farmaceuticas de los mismos. |
-
2014
- 2014-09-30 MX MX2016005142A patent/MX2016005142A/es unknown
- 2014-09-30 PT PT148580905T patent/PT3064498T/pt unknown
- 2014-09-30 CA CA2927641A patent/CA2927641C/en active Active
- 2014-09-30 SI SI201431353T patent/SI3064498T1/sl unknown
- 2014-09-30 AU AU2014344504A patent/AU2014344504C1/en active Active
- 2014-09-30 ES ES14858090T patent/ES2747839T3/es active Active
- 2014-09-30 RU RU2016119135A patent/RU2674977C2/ru active
- 2014-09-30 EP EP14858090.5A patent/EP3064498B1/en active Active
- 2014-09-30 BR BR112016008799-2A patent/BR112016008799B1/pt active IP Right Grant
- 2014-09-30 RS RSP20191238 patent/RS59457B1/sr unknown
- 2014-09-30 US US15/031,410 patent/US10005781B2/en active Active
- 2014-09-30 PL PL14858090T patent/PL3064498T3/pl unknown
- 2014-09-30 DK DK14858090.5T patent/DK3064498T3/da active
- 2014-09-30 WO PCT/CN2014/087906 patent/WO2015062391A1/zh active Application Filing
- 2014-09-30 JP JP2016522010A patent/JP6412563B2/ja active Active
- 2014-09-30 LT LTEP14858090.5T patent/LT3064498T/lt unknown
- 2014-09-30 CN CN201480003662.2A patent/CN104884457B/zh active Active
- 2014-09-30 HU HUE14858090A patent/HUE046314T2/hu unknown
- 2014-10-20 TW TW103136105A patent/TWI675838B/zh active
-
2018
- 2018-05-02 US US15/969,098 patent/US10344034B2/en active Active
-
2019
- 2019-05-20 US US16/416,418 patent/US10633388B2/en active Active
- 2019-09-17 HR HRP20191679 patent/HRP20191679T1/hr unknown
- 2019-09-18 CY CY20191100975T patent/CY1122196T1/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| HRP20191679T1 (hr) | Derivati pirazolopirimidona ili pirolotriazona, postupak pripreme jednakih i njihove farmaceutske uporabe | |
| ES2339456T3 (es) | Derivados de pirrol(2,3-b)piridina activos como inhibidores de quinasa, procedimientos para su preparacion y composiciones farmaceuticas que los comprenden. | |
| RU2509078C2 (ru) | Бициклические гетероциклы в качестве ингибиторов киназы мек | |
| HRP20171748T1 (hr) | 6-amino kinazolina ili 3-cijano derivati kinolina, postupci priprave i njihova farmaceutska uporaba | |
| CN106488910A (zh) | Kras g12c的抑制剂 | |
| CN107849037A (zh) | 用于治疗和预防乙型肝炎病毒感染的新的三环4‑吡啶酮‑3‑甲酸衍生物 | |
| HRP20120351T1 (hr) | Macrociklički derivati kinazolina kao antiproliferativna sredstva | |
| HRP20110498T1 (hr) | Azetidini kao inhibitori mek za liječenje proliferativnih bolesti | |
| ME00058B (me) | Derivati aminoindazola, postupak izrade i međuproizvodi ovog postupka kao medicinski produkti i farmaceutske kompozicije koje ih sadrži | |
| DE60101000D1 (de) | N-heterocyclische derivate als nos inhibitoren | |
| HUP0402352A2 (hu) | Foszfodiészteráz (PDE) 7 inhibitorként alkalmazható pirimidinszármazékok és ezeket tartalmazó gyógyszerkészítmények | |
| NO20063748L (no) | Kinolinderivater og anvendelse derav som mykobakterielle inhibitorer | |
| IS8377A (is) | Arýlindenópyridín og arýlindenópyrimidín og notkun þeirra sem mótlyf A2A viðtaka adenósíns | |
| CN108794487A (zh) | 双并环类核衣壳抑制剂和其作为药物用于治疗乙型肝炎的用途 | |
| Chen et al. | Degrading FLT3-ITD protein by proteolysis targeting chimera (PROTAC) | |
| Silva et al. | Palladium-catalysed synthesis and transformation of quinolones | |
| ES2377610A1 (es) | Preparación de compuestos pirido[2,3-d]pirimidin-7(8h)-ona sustituidos. | |
| EP2342198A1 (en) | Salts of n-[6-cis-2,6-dimethylmorpholin-4yl)pyridine-3yl]-2-methyl-4'-(trifluoromethoxy)[1,1'-biphenyl]-3-carboxamide | |
| Naureen et al. | Synthesis of tetrasubstitutd imidazoles containing indole and their antiurease and antioxidant activities | |
| HRP20191596T1 (hr) | Postupak za pripravu 2-{4-[2-({[2-(4-klorofenil)-1,3-tiazol-4-il]metil}sulfanil)-3,5-dicijan-6- (pirolidin-1-il)piridin-4-il]fenoksi}etil-l-alanil-l-alaninat hidroklorida | |
| ATE447575T1 (de) | Selektive spirocyclische glucocorticoid-rezeptor- modulatoren | |
| DE60206762D1 (de) | Hexahydroazepino[4,5-g]indole und -indoline als 5-ht-rezeptor-liganden | |
| EA201001459A1 (ru) | 2-амино-3-сульфонил-тетрагидропиразоло[1,5-а]пиридопиримидины - антагонисты серотониновых 5-нтрецепторов, способы их получения и применения | |
| CN109988120A (zh) | 一种吲哚胺-2,3-双加氧酶抑制剂及其制备方法和用途 | |
| DE602007008736D1 (de) | 1h-furoä3,2-cü pyrazolverbindungen, die sich als kinaseinhibitoren eignen |