HRP20130902T1 - PIRIDOPIRIMIDINONSKI INHIBITORI PI3Kalfa - Google Patents
PIRIDOPIRIMIDINONSKI INHIBITORI PI3Kalfa Download PDFInfo
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- HRP20130902T1 HRP20130902T1 HRP20130902TT HRP20130902T HRP20130902T1 HR P20130902 T1 HRP20130902 T1 HR P20130902T1 HR P20130902T T HRP20130902T T HR P20130902TT HR P20130902 T HRP20130902 T HR P20130902T HR P20130902 T1 HRP20130902 T1 HR P20130902T1
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- pharmaceutically acceptable
- acceptable salt
- stereoisomers
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- IAAQUOVTPAMQCR-UHFFFAOYSA-N 1h-pyrido[3,2-d]pyrimidin-2-one Chemical compound C1=CC=C2NC(=O)N=CC2=N1 IAAQUOVTPAMQCR-UHFFFAOYSA-N 0.000 title description 2
- 239000003112 inhibitor Substances 0.000 title description 2
- 102100038332 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Human genes 0.000 title 1
- 101710093328 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 59
- 150000003839 salts Chemical class 0.000 claims 52
- 239000012453 solvate Substances 0.000 claims 52
- 239000000203 mixture Substances 0.000 claims 49
- -1 cyano, amino Chemical group 0.000 claims 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 17
- 125000001072 heteroaryl group Chemical group 0.000 claims 16
- 229910052739 hydrogen Inorganic materials 0.000 claims 13
- 239000001257 hydrogen Substances 0.000 claims 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 13
- 125000000217 alkyl group Chemical group 0.000 claims 12
- 125000000547 substituted alkyl group Chemical group 0.000 claims 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims 9
- 125000001475 halogen functional group Chemical group 0.000 claims 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 7
- 125000003118 aryl group Chemical group 0.000 claims 7
- 125000003710 aryl alkyl group Chemical group 0.000 claims 6
- 150000002431 hydrogen Chemical group 0.000 claims 6
- 125000003545 alkoxy group Chemical group 0.000 claims 5
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 5
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 4
- 125000003282 alkyl amino group Chemical group 0.000 claims 4
- 125000001188 haloalkyl group Chemical group 0.000 claims 4
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims 4
- 125000001724 1,2,3-oxadiazol-4-yl group Chemical group [H]C1=C(*)N=NO1 0.000 claims 3
- 125000004503 1,2,3-oxadiazol-5-yl group Chemical group O1N=NC=C1* 0.000 claims 3
- 125000001766 1,2,4-oxadiazol-3-yl group Chemical group [H]C1=NC(*)=NO1 0.000 claims 3
- 125000004505 1,2,4-oxadiazol-5-yl group Chemical group O1N=CN=C1* 0.000 claims 3
- 125000004509 1,3,4-oxadiazol-2-yl group Chemical group O1C(=NN=C1)* 0.000 claims 3
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims 3
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims 3
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims 3
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims 3
- 206010028980 Neoplasm Diseases 0.000 claims 3
- 125000004104 aryloxy group Chemical group 0.000 claims 3
- 201000011510 cancer Diseases 0.000 claims 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims 3
- 125000004663 dialkyl amino group Chemical group 0.000 claims 3
- 125000004438 haloalkoxy group Chemical group 0.000 claims 3
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims 3
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims 3
- 125000000336 imidazol-5-yl group Chemical group [H]N1C([H])=NC([H])=C1[*] 0.000 claims 3
- 125000004284 isoxazol-3-yl group Chemical group [H]C1=C([H])C(*)=NO1 0.000 claims 3
- 125000004498 isoxazol-4-yl group Chemical group O1N=CC(=C1)* 0.000 claims 3
- 125000004499 isoxazol-5-yl group Chemical group O1N=CC=C1* 0.000 claims 3
- 125000004287 oxazol-2-yl group Chemical group [H]C1=C([H])N=C(*)O1 0.000 claims 3
- 125000003145 oxazol-4-yl group Chemical group O1C=NC(=C1)* 0.000 claims 3
- 125000004304 oxazol-5-yl group Chemical group O1C=NC=C1* 0.000 claims 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 3
- 125000004289 pyrazol-3-yl group Chemical group [H]N1N=C(*)C([H])=C1[H] 0.000 claims 3
- 125000004497 pyrazol-5-yl group Chemical group N1N=CC=C1* 0.000 claims 3
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims 3
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims 3
- 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 claims 3
- 125000004496 thiazol-5-yl group Chemical group S1C=NC=C1* 0.000 claims 3
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims 2
- 206010006187 Breast cancer Diseases 0.000 claims 2
- 208000026310 Breast neoplasm Diseases 0.000 claims 2
- 206010008342 Cervix carcinoma Diseases 0.000 claims 2
- 206010009944 Colon cancer Diseases 0.000 claims 2
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims 2
- 206010033128 Ovarian cancer Diseases 0.000 claims 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 2
- 208000015634 Rectal Neoplasms Diseases 0.000 claims 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims 2
- 201000010881 cervical cancer Diseases 0.000 claims 2
- 208000029742 colonic neoplasm Diseases 0.000 claims 2
- 125000002541 furyl group Chemical group 0.000 claims 2
- 208000005017 glioblastoma Diseases 0.000 claims 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 2
- 125000002883 imidazolyl group Chemical group 0.000 claims 2
- 125000000842 isoxazolyl group Chemical group 0.000 claims 2
- 125000001715 oxadiazolyl group Chemical group 0.000 claims 2
- 125000002971 oxazolyl group Chemical group 0.000 claims 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims 2
- 125000002098 pyridazinyl group Chemical group 0.000 claims 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims 2
- 206010038038 rectal cancer Diseases 0.000 claims 2
- 201000001275 rectum cancer Diseases 0.000 claims 2
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims 2
- 125000003831 tetrazolyl group Chemical group 0.000 claims 2
- 125000000335 thiazolyl group Chemical group 0.000 claims 2
- 125000001544 thienyl group Chemical group 0.000 claims 2
- 125000001425 triazolyl group Chemical group 0.000 claims 2
- GYIRYQBREBFQOD-UHFFFAOYSA-N 2-amino-8-ethyl-4-methylpyrido[2,3-d]pyrimidin-7-one Chemical compound NC1=NC(C)=C2C=CC(=O)N(CC)C2=N1 GYIRYQBREBFQOD-UHFFFAOYSA-N 0.000 claims 1
- FCRAMMPIIQIEGZ-UHFFFAOYSA-N 8-ethyl-2-(ethylamino)-4-methylpyrido[2,3-d]pyrimidin-7-one Chemical compound C1=CC(=O)N(CC)C2=NC(NCC)=NC(C)=C21 FCRAMMPIIQIEGZ-UHFFFAOYSA-N 0.000 claims 1
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims 1
- 206010014733 Endometrial cancer Diseases 0.000 claims 1
- 206010014759 Endometrial neoplasm Diseases 0.000 claims 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
- 206010041067 Small cell lung cancer Diseases 0.000 claims 1
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 1
- 208000024770 Thyroid neoplasm Diseases 0.000 claims 1
- 125000002252 acyl group Chemical group 0.000 claims 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims 1
- 125000004103 aminoalkyl group Chemical group 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- RODCZGBQVPTRTI-UHFFFAOYSA-N but-1-en-2-yl(tributyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C(=C)CC RODCZGBQVPTRTI-UHFFFAOYSA-N 0.000 claims 1
- 125000004181 carboxyalkyl group Chemical group 0.000 claims 1
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims 1
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000000945 filler Substances 0.000 claims 1
- 206010017758 gastric cancer Diseases 0.000 claims 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims 1
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims 1
- 210000004072 lung Anatomy 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- 201000001441 melanoma Diseases 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 230000004048 modification Effects 0.000 claims 1
- 238000012986 modification Methods 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 238000000926 separation method Methods 0.000 claims 1
- 208000000649 small cell carcinoma Diseases 0.000 claims 1
- 208000000587 small cell lung carcinoma Diseases 0.000 claims 1
- 201000011549 stomach cancer Diseases 0.000 claims 1
- 125000003107 substituted aryl group Chemical group 0.000 claims 1
- 201000002510 thyroid cancer Diseases 0.000 claims 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—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
-
- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/02—Suppositories; Bougies; Bases therefor; Ovules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dispersion Chemistry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
PIRIDOPIRIMIDINONSKI INHIBITORI PI3KALFA
Claims (54)
1. Spoj formule I:
[image]
ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat, gdje
R1 je vodik, izborno supstituirani alkil, izborno supstituirani cikloalkil, izborno supstituirani cikloalkilalkil, izborno supstituirani aril, izborno supstituirani arilalkil, izborno supstituirani heterocikloalkil, izborno supstituirani heterocikloalkilalkil, izborno supstituirani heteroaril ili izborno supstituirani heteroarilalkil;
R2 je vodik ili alkil, gdje je alkil izborno supstituiran sa 1, 2, 3, 4 ili 5 R8 grupa;
X je -NR3-;
R3 je vodik;
R4 je izborno supstituirani alkil;
R5 je vodik; i
R6 je fenil, acil, ili heteroaril, gdje su fenil i heteroaril izborno supstituirani sa 1, 2, 3, 4 ili 5 R9 grupa;
svako R8, kada je prisutno, je nezavisno hidroksi, halo, alkoksi, haloalkoksi, amino, alkilamino, dialkilaminoalkil ili alkoksialkilamino; i
svako R9, kada je prisutno, je nezavisno halo, alkil, haloalkil, alkoksi, haloalkoksi, cijano, amino, alkilamino, dialkilamino, alkoksialkil, carboksialkil, alkoksikarbonil, aminoalkil, cikloalkil, aril, arilalkil, ariloksi, heterocikloalkil ili heteroaril i gdje cikloalkil, aril, heterocikloalkil i heteroaril, svaki pojedinačno ili kao dio druge grupe unutar R9, su nezavisno izborno supstituirani sa 1, 2, 3 ili 4 grupe izabrane od halo, alkil, haloalkil, hidroksi, alkoksi, haloalkoksi, amino, alkilamino i dialkilamino.
2. Spoj prema patentnom zahtjevu 1, naznačen time što je R1 jednako vodik, izborno supstituirani alkil, izborno supstituirani cikloalkil, izborno supstituirani heterocikloalkilalkil ili izborno supstituirani arilalkil; X je -NH-; R2 je vodik ili alkil, gdje je alkil izborno supstituiran sa jednom ili dvije R8 grupe; R4 je alkil; R5 je vodik; R6 je fenil ili heteroaril, gdje su fenil i heteroaril izborno supstituirani sa jednom, dvije ili tri R9 grupe; svako R8, kada je prisutno, je nezavisno amino, alkilamino, dialkilamino ili halo; i svako R9, kada je prisutno, je nezavisno alkil, arilalkil, cijano, aril, alkoksikarbonil ili halo; ili njegov pojedinačni izomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
3. Spoj prema patentnom zahtjevu 1, naznačen time što je R2 jednako vodik; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
4. Spoj prema patentnom zahtjevu 3, naznačen time što je R4 jednako metil; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
5. Spoj prema patentnom zahtjevu 3, naznačen time što je R1 jednako izborno supstituirani alkil ili cikloalkil; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
6. Spoj prema patentnom zahtjevu 4, naznačen time što je R1 jednako izborno supstituirani alkil; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
7. Spoj prema patentnom zahtjevu 3, naznačen time što je R6 jednako fenil izborno supstituiran sa 1, 2 ili 3 R9 grupe; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
8. Spoj prema patentnom zahtjevu 7, naznačen time što je svako R9, kada je prisutno, nezavisno jednako aril, halo, alkoksi, ariloksi ili haloalkil; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
9. Spoj prema patentnom zahtjevu 7, naznačen time što je R4 jednako metil; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
10. Spoj prema patentnom zahtjevu 3, naznačen time što je R6 jednako heteroaril izborno supstituiran sa 1, 2 ili 3 R9 grupe; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
11. Spoj prema patentnom zahtjevu 10, naznačen time što je svako R9, kada je prisutno, nezavisno jednako alkil, arilalkil, cijano, aril, alkoksikarbonil ili halo; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
12. Spoj prema patentnom zahtjevu 3, naznačen time što je R6 jednako pirazolil, imidazolil, tienil, tiazolil, oksazolil, izoksazolil, oksadiazolil, furanil, pirolil, triazolil ili tetrazolil; od kojih je svaki izborno supstituiran sa 1, 2 ili 3 R9 grupe; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
13. Spoj prema patentnom zahtjevu 3, naznačen time što je R6 jednako pirazol-3-il, pirazol-4-il, pirazol-5-il, imidazol-2-il, imidazol-4-il, imidazol-5-il, tien-2-il, tien-3-il, tiazol-2-il, tiazol-4-il, tiazol-5-il, oksazol-2-il, oksazol-4-il, oksazol-5-il, izoksazol-3-il, izoksazol-4-il, izoksazol-5-il, 1,2,3-oksadiazol-4-il, 1,2,3-oksadiazol-5-il, 1,3,4-oksadiazol-2-il, 1,2,4-oksadiazol-3-il, 1,2,4-oksadiazol-5-il, furan-2-il, furan-3-il, pirol-2-il, pirol-3-il, triazol-4-il, triazol-5-il ili tetrazol-5-il; od kojih je svaki izborno supstituiran sa 1, 2 ili 3 R9 grupe; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
14. Spoj prema patentnom zahtjevu 12, naznačen time što je R4 jednako metil; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
15. Spoj prema patentnom zahtjevu 3, naznačen time što je R6 jednako pirazinil, pirimidinil ili piridazinil, od kojih je svaki izborno supstituiran sa 1, 2 ili 3 R9 grupe; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
16. Spoj prema patentnom zahtjevu 15, naznačen time što je R4 jednako metil; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
17. Spoj prema patentnom zahtjevu 1, naznačen time što je R2 jednako vodik, R4 je metil, R1 je izborno supstituirani alkil ili cikloalkil, i R6 je fenil izborno supstituiran sa 1, 2 ili 3 R9 grupe; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
18. Spoj prema patentnom zahtjevu 1, naznačen time što je R2 jednako vodik, R4 je metil, R1 je izborno supstituirani alkil ili cikloalkil, i R6 je heteroaril izborno supstituiran sa 1, 2 ili 3 R9 grupe; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
19. Spoj prema patentnom zahtjevu 3, naznačen time što je R1 jednako heterocikloalkil i R4 je metil; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
20. Spoj prema patentnom zahtjevu 19, naznačen time što je R6 jednako fenil izborno supstituiran sa 1, 2 ili 3 R9 grupe; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
21. Spoj prema patentnom zahtjevu 19, naznačen time što je R6 jednako heteroaril izborno supstituiran sa 1, 2 ili 3 R9 grupe; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
22. Spoj prema patentnom zahtjevu 3, naznačen time što je R1 jednako heterocikloalkilalkil i R4 je metil; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
23. Spoj prema patentnom zahtjevu 22, naznačen time što je R6 jednako fenil izborno supstituiran sa 1, 2 ili 3 R9 grupe; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
24. Spoj prema patentnom zahtjevu 22, naznačen time što je R6 jednako heteroaril izborno supstituiran sa 1, 2 ili 3 R9 grupe; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
25. Spoj prema patentnom zahtjevu 1, naznačen time što je R2 jednako alkil izborno supstituiran sa 1, 2 ili 3 R9 grupe; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva so ili solvat.
26. Spoj prema patentnom zahtjevu 25, naznačen time što je R4 jednako metil; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
27. Spoj prema patentnom zahtjevu 25, naznačen time što je R1 jednako izborno supstituirani alkil ili cikloalkil; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
28. Spoj prema patentnom zahtjevu 25, naznačen time što je R1 jednako izborno supstituirani alkil; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
29. Spoj prema patentnom zahtjevu 25, naznačen time što je R6 jednako fenil izborno supstituiran sa 1, 2 ili 3 R9 grupe; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
30. Spoj prema patentnom zahtjevu 29, naznačen time što je svaki R9, kada je prisutan, nezavisno jednak aril, halo, alkoksi, ariloksi i haloalkil; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
31. Spoj prema patentnom zahtjevu 29, naznačen time što je R4 jednako metil; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat
32. Spoj prema patentnom zahtjevu 25, naznačen time što je R6 jednako heteroaril izborno supstituiran sa 1, 2 ili 3 R9 grupe; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
33. Spoj prema patentnom zahtjevu 32, naznačen time što je svaki R9, kada je prisutan, nezavisno jednak alkil, arilalkil, cijano, aril, alkoksikarbonil ili halo; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
34. Spoj prema patentnom zahtjevu 25, naznačen time što je R6 jednak pirazolil, imidazolil, tienil, tiazolil, oksazolil, izoksazolil, oksadiazolil, furanil, pirolil, triazolil ili tetrazolil; od kojih je svaki izborno supstituiran sa 1, 2 ili 3 R9 grupe; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
35. Spoj prema patentnom zahtjevu 25, naznačen time što je R6 jednako pirazol-3-il, pirazol-4-il, pirazol-5-il, imidazol-2-il, imidazol-4-il, imidazol-5-il, tien-2-il, tien-3-il, tiazol-2-il, tiazol-4-il, tiazol-5-il, oksazol-2-il, oksazol-4-il, oksazol-5-il, izoksazol-3-il, izoksazol-4-il, izoksazol-5-il, 1,2,3-oksadiazol-4-il, 1,2,3-oksadiazol-5-il, 1,3,4-oksadiazol-2-il, 1,2,4-oksadiazol-3-il, 1,2,4-oksadiazol-5-il, furan-2-il, furan-3-il, pirol-2-il, pirol-3-il, triazol-4-il, triazol-5-il ili tetrazol-5-il; od kojih je svaki izborno supstituiran sa 1, 2 ili 3 R9 grupe; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
36. Spoj prema patentnom zahtjevu 34, naznačen time što je R4 jednako metil; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
37. Spoj prema patentnom zahtjevu 25, naznačen time što je R6 jednako pirazinil, pirimidinil ili piridazinil, od kojih je svaki izborno supstituiran sa 1, 2 ili 3 R9 grupe; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
38. Spoj prema patentnom zahtjevu 37, naznačen time što je R4 jednako metil; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
39. Spoj prema patentnom zahtjevu 1, naznačen time što je R2 jednako vodik, R4 je metil, R1 je izborno supstituirani alkil ili cikloalkil, i R6 je fenil izborno supstituiran sa 1, 2 ili 3 R9 grupe; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
40. Spoj prema patentnom zahtjevu 1, naznačen time što je R2 jednako vodik, R4 je metil, R1 je izborno supstituirani alkil ili cikloalkil, i R6 je heteroaril izborno supstituiran sa 1, 2, 3, 4 ili 5 R9 grupa; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
41. Spoj prema patentnom zahtjevu 25, naznačen time što je R1 jednako heterocikloalkil ili heterocikloalkilalkil i R4 je metil; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
42. Spoj prema patentnom zahtjevu 41, naznačen time što je R6 jednako fenil izborno supstituiran sa 1, 2 ili 3 R9 grupe; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
43. Spoj prema patentnom zahtjevu 41, naznačen time što je R6 jednako heteroaril izborno supstituiran sa 1, 2 ili 3 R9 grupe; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
44. Spoj prema patentnom zahtjevu 18, naznačen time što je R1 jednako alkil ili cikloalkil; R2 je vodik; R4 je metil; R6 je pirazol-3-il, pirazol-4-il, pirazol-5-il, imidazol-2-il, imidazol-4-il, imidazol-5-il, tien-2-il, tien-3-il, tiazol-2-il, tiazol-4-il, tiazol-5-il, oksazol-2-il, oksazol-4-il, oksazol-5-il, izoksazol-3-il, izoksazol-4-il, izoksazol-5-il, 1,2,3-oksadiazol-4-il, 1,2,3-oksadiazol-5-il, 1,3,4-oksadiazol-2-il, 1,2,4-oksadiazol-3-il, 1,2,4-oksadiazol-5-il, furan-2-il, furan-3-il, pirol-2-il, pirol-3-il, triazol-4-il, triazol-5-il ili tetrazol-5-il; od kojih je svaki izborno supstituiran sa jednim R9, pri čemu je R9, kada je prisutan, jednak metil, benzil, cijano, fenil ili N-terc-butoksikarbonil; ili njegov pojedinačni stereoizomer ili smjesa stereoizomera i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
45. Spoj prema patentnom zahtjevu 1, naznačen time što je navedeni spoj izabran od
[image]
[image]
i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
46. Spoj prema patentnom zahtjevu 45, naznačen time što spoj jednak:
[image]
izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
47. Spoj izabran od
[image]
i izborno kao njegova farmaceutski prihvatljiva sol ili solvat.
48. Farmaceutska kompozicija koja sadrži spoj prema bilo kojem od patentnih zahtjeva 1 do 47, ili njegov pojedinačni stereoizomer ili smjesu stereoizomera, izborno kao njegovu farmaceutski prihvatljivu sol ili solvat, i farmaceutski prihvatljiv nosač, inertni punitelj ili razblaživač.
49. Spoj, ili njegov pojedinačni stereoizomer ili smjesa stereoizomera, izborno kao njegova farmaceutski prihvatljiva sol ili solvat, prema bilo kojem od patentnih zahtjeva 1 do 47, izborno kao njegova farmaceutski prihvatljiva sol ili solvat za uporabu u medicini.
50. Spoj, ili njegov pojedinačni stereoizomer ili smjesa stereoizomera, izborno kao njegova farmaceutski prihvatljiva sol ili solvat, prema bilo kojem od patentnih zahtjeva 1 do 47, izborno kao njegova farmaceutski prihvatljiva sol ili solvat, za uporabu u liječenju kancera.
51. Spoj, ili njegov pojedinačni stereoizomer ili smjesa stereoizomera, prema patentnom zahtjevu 50, naznačen time što je kancer – kancer dojke, kancer debelog crijeva, kancer rektuma, kancer endometrija, karcinom želudca, glioblastom, hepatostanični karcinom, sitnostanični kancer pluća, nesitnostanični kancer pluća, melanom, kancer jajnika, kancer grlića materice, kancer pankreasa, karcinom prostate, akutna mijelogena leukemija (AML), kronična mijelogena leukemija (CML) ili karcinom tireoidee.
52. Spoj, ili njegov pojedinačni stereoizomer ili smjesa stereoizomera, prema patentnom zahtjevu 50, naznačen time što je kancer kancer jajnika, kancer grlića materice, kancer dojke, kancer debelog crijeva, kancer rektuma ili glioblastom.
53. Postupak za pripremu spoja prema patentnom zahtjevu 1, naznačen time što sadrži:
(a) reakciju intermedijera formule 7(a):
[image]
gdje je R6 jednako fenil ili heteroaril, svaki izborno supstituiran sa 1, 2, 3, 4 ili 5 R9 grupa; sa intermedijerom formule R2NH2 da bi se proizveo spoj prema patentnom zahtjevu 1 prema formuli I(a):
[image]
ili
(b) reakciju intermedijera formule 18:
[image]
sa tributil-1-etilvinilkalajem ili sa intermedijerom formule R6B(OH)2, gdje je R6 jednako fenil ili heteroaril svaki izborno supstituiran sa 1, 2, 3, 4 ili 5 R9 grupa da bi se proizveo, respektivno, spoj formule I(a) ili I(b):
[image]
ili
(c) reakciju intermedijera formule 25(a):
[image]
sa intermedijerom R2NH2 da bi se proizveo spoj formule I(a):
[image]
i
(d) izborno dodatno razdvajanje pojedinačnih izomera; i
(e) izborno dodatnu modifikaciju jedne od R1, R2, R4 i R6 grupa.
54. Spoj koji je:
8-etil-2-(etilamino)-4-metilpirido[2,3-d]pirimidin-7(8H)-on; ili
2-amino-8-etil-4-metilpirido[2,3-d]pirimidin-7(8H)-on.
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