HRP20140478T1 - Novi derivati (6-okso-1,6-dihidropirimidin-2-il)amida, njihovo dobivanje, te farmaceutska upotreba kao inhibitora fosforilacije akt - Google Patents
Novi derivati (6-okso-1,6-dihidropirimidin-2-il)amida, njihovo dobivanje, te farmaceutska upotreba kao inhibitora fosforilacije akt Download PDFInfo
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- HRP20140478T1 HRP20140478T1 HRP20140478AT HRP20140478T HRP20140478T1 HR P20140478 T1 HRP20140478 T1 HR P20140478T1 HR P20140478A T HRP20140478A T HR P20140478AT HR P20140478 T HRP20140478 T HR P20140478T HR P20140478 T1 HRP20140478 T1 HR P20140478T1
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- Prior art keywords
- morpholin
- oxo
- dihydropyrimidin
- acetamide
- oxoethyl
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- 239000003112 inhibitor Substances 0.000 title claims 2
- 230000026731 phosphorylation Effects 0.000 title claims 2
- 238000006366 phosphorylation reaction Methods 0.000 title claims 2
- XQCZBXHVTFVIFE-UHFFFAOYSA-N 2-amino-4-hydroxypyrimidine Chemical class NC1=NC=CC(O)=N1 XQCZBXHVTFVIFE-UHFFFAOYSA-N 0.000 title 1
- -1 heteroaryl radical Chemical class 0.000 claims 46
- 150000003254 radicals Chemical group 0.000 claims 20
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 16
- 125000003545 alkoxy group Chemical group 0.000 claims 12
- 125000000217 alkyl group Chemical group 0.000 claims 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 10
- 125000005843 halogen group Chemical group 0.000 claims 9
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 8
- 206010028980 Neoplasm Diseases 0.000 claims 6
- 150000003839 salts Chemical class 0.000 claims 6
- 125000003118 aryl group Chemical group 0.000 claims 5
- 150000007529 inorganic bases Chemical class 0.000 claims 5
- 150000007522 mineralic acids Chemical class 0.000 claims 5
- 229910052757 nitrogen Inorganic materials 0.000 claims 5
- 150000007524 organic acids Chemical class 0.000 claims 5
- 235000005985 organic acids Nutrition 0.000 claims 5
- 150000007530 organic bases Chemical class 0.000 claims 5
- 201000011510 cancer Diseases 0.000 claims 4
- 125000005842 heteroatom Chemical group 0.000 claims 4
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 4
- 229910052760 oxygen Inorganic materials 0.000 claims 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 4
- 229910052717 sulfur Inorganic materials 0.000 claims 4
- 125000000304 alkynyl group Chemical group 0.000 claims 3
- 238000000034 method Methods 0.000 claims 3
- 125000001424 substituent group Chemical group 0.000 claims 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 2
- 125000003342 alkenyl group Chemical group 0.000 claims 2
- 125000004414 alkyl thio group Chemical group 0.000 claims 2
- 125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 claims 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 2
- 238000002512 chemotherapy Methods 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 229940079593 drug Drugs 0.000 claims 2
- 229910052731 fluorine Inorganic materials 0.000 claims 2
- 229910052736 halogen Inorganic materials 0.000 claims 2
- 150000002367 halogens Chemical class 0.000 claims 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 2
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 claims 1
- 206010005003 Bladder cancer Diseases 0.000 claims 1
- 206010005949 Bone cancer Diseases 0.000 claims 1
- 208000018084 Bone neoplasm Diseases 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 208000002927 Hamartoma Diseases 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 206010023825 Laryngeal cancer Diseases 0.000 claims 1
- 206010027476 Metastases Diseases 0.000 claims 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
- 206010039491 Sarcoma 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
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims 1
- 210000000988 bone and bone Anatomy 0.000 claims 1
- 210000004556 brain Anatomy 0.000 claims 1
- 201000000220 brain stem cancer Diseases 0.000 claims 1
- 210000001072 colon Anatomy 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 229940127089 cytotoxic agent Drugs 0.000 claims 1
- 239000002254 cytotoxic agent Substances 0.000 claims 1
- 231100000599 cytotoxic agent Toxicity 0.000 claims 1
- 125000001070 dihydroindolyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims 1
- 230000002357 endometrial effect Effects 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 208000005017 glioblastoma Diseases 0.000 claims 1
- 201000005787 hematologic cancer Diseases 0.000 claims 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims 1
- 125000001041 indolyl group Chemical group 0.000 claims 1
- 239000000543 intermediate Substances 0.000 claims 1
- 210000003734 kidney Anatomy 0.000 claims 1
- 206010023841 laryngeal neoplasm Diseases 0.000 claims 1
- 210000000867 larynx Anatomy 0.000 claims 1
- 201000004962 larynx cancer Diseases 0.000 claims 1
- 239000007788 liquid Substances 0.000 claims 1
- 210000004185 liver Anatomy 0.000 claims 1
- 210000004072 lung Anatomy 0.000 claims 1
- 201000007275 lymphatic system cancer Diseases 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- 238000002483 medication Methods 0.000 claims 1
- 201000001441 melanoma Diseases 0.000 claims 1
- FNVXODZLOZEOPT-UHFFFAOYSA-N n-(3,4-dihydro-2h-1,4-benzoxazin-8-yl)-2-(6-morpholin-4-yl-4-oxo-1h-pyrimidin-2-yl)acetamide Chemical compound C=1C=CC=2NCCOC=2C=1NC(=O)CC(NC(=O)C=1)=NC=1N1CCOCC1 FNVXODZLOZEOPT-UHFFFAOYSA-N 0.000 claims 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims 1
- 210000001672 ovary Anatomy 0.000 claims 1
- 125000004043 oxo group Chemical group O=* 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 125000005936 piperidyl group Chemical group 0.000 claims 1
- 210000002307 prostate Anatomy 0.000 claims 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 1
- 229920006395 saturated elastomer Polymers 0.000 claims 1
- 239000007787 solid Substances 0.000 claims 1
- 201000000498 stomach carcinoma Diseases 0.000 claims 1
- 125000001544 thienyl group Chemical group 0.000 claims 1
- 201000002510 thyroid cancer Diseases 0.000 claims 1
- 210000001685 thyroid gland Anatomy 0.000 claims 1
- 210000003932 urinary bladder Anatomy 0.000 claims 1
- 201000005112 urinary bladder cancer Diseases 0.000 claims 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/20—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D239/22—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to ring carbon atoms
-
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- 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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- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C07—ORGANIC CHEMISTRY
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- 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
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- C07D403/10—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 aromatic rings
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- 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
- C07D403/12—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 chain containing hetero atoms as chain links
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- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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Claims (17)
1. Produkti formule (I):
[image]
,
naznačeni time što:
R1 predstavlja arilni ili heteroarilni radikal, izborno supstituiran s jednim ili više radikala koji mogu biti isti ili različiti i bira ih se između atoma halogena i hidroksilnih, CN, nitro, -COOH, -COOalk, -CONRxRy, -NRx-CORy, -CORy, -NRxCO2Rz, alkoksi, fenoksi, alkiltio, alkilnih, alkenilnih, alkinilnih, cikloalkilninih, O-cikloalkilnih, heterocikloalkilnih, arilnih i heteroarilnih radikala;
gdje su potonji alkoksi, fenoksi, alkiltio, alkilni, alkenilni, alkinilni, heterocikloalkilni, arilni i heteroarilni radikali i sami izborno supstituirani s jednim ili više radikala koji mogu biti isti ili različiti i bira ih se između atoma halogena i hidroksilnih, alkoksi, NRvRw, heterocikloalkilnih ili heteroarilnih radikala;
gdje su arilni i heteroarilni radikali također izborno supstituirani s jednim ili više alkilnih i alkoksi radikala, koji su i sami izborno supstituirani s jednim ili više atoma halogena;
gdje heterocikloalkilni i heteroarilni radikali mogu dodatno sadržavati okso radikal;
R predstavlja atom vodika ili inače tvori, s R1, zasićeni ili djelomično ili posve nezasićeni 5- ili 6-eročlani prsten, kondenziran s arilnim ili heteroarilnim ostatkom, i izborno sadrži jedan ili više drugih heteroatoma, koje se bira između O, S, N, NH i Nalk, gdje je taj biciklički radikal izborno supstituiran s jednim ili više radikala koji mogu biti isti ili različiti i bira ih se između atoma halogena i CO-NH2, hidroksilnih, alkilnih i alkoksi radikala;
gdje je potonji alkilni radikal i sam izborno supstituiran s hidroksilnim, alkoksi, NH2, NHalk ili N(alk)2 radikalom;
R2 i R3, koji mogu biti isti ili različiti, neovisno predstavljaju atom vodika, atom halogena ili alkilni radikal, izborno supstituiran s jednim ili više atoma halogena;
R4 predstavlja atom vodika;
R5 predstavlja atom vodika ili alkilni radikal, izborno supstituiran s jednim ili više atoma halogena;
NRxRy je takav da Rx predstavlja atom vodika ili alkilni radikal, a Ry predstavlja atom vodika ili cikloalkilni radikal ili alkilni radikal, izborno supstituiran s jednim ili više radikala koji mogu biti isti ili različiti i bira ih se između hidroksilnih, alkoksi, NRvRw i heterocikloalkilnih radikala; ili Rx i Ry tvore, s atomom dušika na kojeg su vezani, prstenasti radikal, koji sadrži od 3 do 10 članova prstena i izborno jedan ili više drugih heteroatoma, koje se bira između O, S, NH i N-alkila, gdje je taj radikal izborno supstituiran;
NRvRw je takav da Rv predstavlja atom vodika ili alkilni radikal, a Rw predstavlja atom vodika ili cikloalkilni radikal, CO2alk, ili alkilni radikal, izborno supstituiran s jednim ili više radikala koji mogu biti isti ili različiti i bira ih se između hidroksilnih, alkoksi i heterocikloalkilnih radikala; ili Rv i Rw tvore, s atomom dušika na kojeg su vezani, prstenasti radikal, koji sadrži od 3 do 10 članova prstena i izborno jedan ili više drugih heteroatoma, koje se bira između O, S, NH i N-alkila, gdje je taj prstenasti radikal izborno supstituiran;
prstenasti radikali koje Rx i Ry odnosno Rv i Rw mogu tvoriti s atomom dušika na kojeg su vezani su izborno supstituiran s jednim ili više radikala koji mogu biti isti ili različiti i bira ih se između atoma halogena i alkilnih, hidroksilnih, okso, alkoksi, NH2, NHalk i N(alk)2 radikala;
Rz predstavlja vrijednosti za Ry osim za vodik;
Rx, Ry i Rz u -NRxCORy, -CORy i CO2Rz radikalima se bira između značenja navedenih gore za Rx, Ry i Rz;
svi gore navedeni alkilni (alk), alkoksi i alkiltio, radikali su nerazgranati ili razgranati i sadrže od 1 do 6 atomi ugljika, gdje su navedeni produkti formule (I) u svim mogućim racemičnim, enantiomernim i dijastereoizomernim stereoizomernim oblicima, a također i adicijske soli s anorganske i organske kiseline ili s anorganskim i organskama bazama, navedenih produkata formule (I).
2. Produkti formule (I), u skladu s patentnim zahtjevom 1, naznačeni time što:
R1 predstavlja fenilni, piridinski, tienilni, benzoksazolilni, benzofurilni, indazolilni, indolilni, benzotienilni, benzimidazolilni, benzoksazinilni ili tetrahidrokinolilni radikal, izborno supstituiran s jednim ili više radikala koji mogu biti isti ili različiti i bira ih se između atoma halogena i CN, nitro, -COOH, -COOalk, -NRxRy, alkoksi, alkilnih, alkinilnih i cikloalkilnih radikala;
gdje su potonji alkoksi, alkil i alkinilni radikali i sami izborno supstituirani s jednim ili više radikala koji mogu biti isti ili različiti i bira ih se između atoma halogena i hidroksilnih, alkoksi, NRvRw, piperidilnih, pirolidinilninih ili heteroarilnih radikala;
gdje su fenilni i heteroarilni radikali također izborno supstituirani s jednim ili više alkilnih i alkoksi radikala;
R predstavlja atom vodika ili inače tvori, s R1, benzoksazinilni, dihidroindolilni, tetrahidroizokinolilni, tetrahidrokinolilni ili dihidropirolopiridilni prsten, gdje su ti prsteni izborno supstituirani s jednim ili više radikala koji mogu biti isti ili različiti i bira ih se između atoma halogena i CO-NH2, hidroksilnih, alkilnih i alkoksi radikala;
gdje je potonji alkilni radikal i sam izborno supstituiran s hidroksilnim, alkoksi, NH2, NHalk ili N(alk)2 radikalom;
R2 i R3, koji mogu biti isti ili različiti, neovisno predstavljaju atom vodika, atom fluora ili alkilni radikal;
R4 predstavlja atom vodika;
R5 predstavlja atom vodika ili alkilni radikal;
NRxRy je takav da Rx predstavlja atom vodika ili alkilni radikal, a Ry predstavlja atom vodika ili alkilni radikal; ili Rx i Ry tvore, s atomom dušika na kojeg su vezani, prstenasti radikal, koji sadrži od 3 do 10 članova prstena i izborno jedan ili više drugih heteroatoma, koje se bira između O, S, NH i N-alkila, gdje je taj prstenasti radikal izborno supstituiran;
NRvRw je takav da Rv predstavlja atom vodika ili alkilni radikal, a Rw predstavlja atom vodika ili alkilni radikal;
svi gore navedeni alkil (alk) i alkoksi radikali su nerazgranati ili razgranati i sadrže od 1 do 6 atomi ugljika, gdje su navedeni produkti formule (I) u svim mogućim racemičnim, enantiomernim i dijastereoizomernim stereoizomernim oblicima, a također i adicijske soli s anorganske i organske kiseline ili s anorganskim i organskama bazama, navedenih produkata formule (I).
3. Produkti formule (I), u skladu s bilo kojim od patentnih zahtjeva 1 i 2, naznačeni time što odgovaraju sljedećim formulama:
– 2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]-N-fenilacetamidu
– N-(4-fluorfenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(3-klorfenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-[3-(dimetilamino)fenil]-2-[4-(morfolin-4-il)-6-okso-1,6-dihidroirimidin-2-il]acetamidu
– N-(2,4-difluorfenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(3,4-difluorfenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– 2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]-N-(tiofen-3-il)acetamidu
– N-(4-fluor-3-metoksifenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(2-fluorfenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(2-metilfenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(2-metoksifenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(2,3-difluorfenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(3,5-difluorfenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(3-fluorfenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(4-klorfenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(3-metoksifenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– 2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]-N-[3-(trifluormetil)fenil]acetamidu
– N-(3-bromfenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-[3-(2-metilpropan-2-il)fenil]-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– metil-3-({[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetil}amino)benzoatu
– 3-({[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetil}amino)benzojevoj kiselini
– 2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]-N-[3-(propan-2-il)fenil]acetamidu
– N-(3-metilfenil-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(3-cijano-4-fluorfenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(1H-indazol-6-il)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(3-cijanofenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(5-fluorpiridin-2-il)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(4-fluor-3-metilfenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(3-klor-4-fluorfenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– 2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]-N-(piridin-3-il)acetamidu
– N-(4-fluor-2-metilfenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(3-hidroksifenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(3-brom-4-fluorfenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– 2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]-N-(3,4,5-trifluorfenil)acetamidu
– N-[4-fluor-3-(hidroksimetil)fenil]-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(3-ciklopropilefenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(2-hidroksifenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-[3-(difluormetoksi)fenil]-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(4-fluor-3-metoksifenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]propanamidu
– N-(2,3-dimetilfenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(2-fluor-3-metilfenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(1,3-benzoksazol-4-il)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– 2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]-N-[3-(trifluormetoksi)fenil]acetamidu
– 2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]-N-[3-(propan-2-iloksi)fenil]acetamidu
– N-(4-fluor-2-metoksifenil)-2-[4-(morfolin-4-il)-5-okso-1,6-dihidropirimidin-2-il]acetamidu
– 2-metilpropan-2-il-{2-[3-({[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetil}amino)fenil]etil}karbamatu
– N-[4-fluor-3-(trifluormetil)fenil]-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(3-etinilfenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-[3-(ciklopentiloksi)fenil]-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(4-fluor-2-hidroksifenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– 2-[2-(2,3-dihidro-1H-indol-1-il)-2-oksoetil]-6-(morfolin-4-il)pirimidin-4(3H)-onu
– N-(3-ciklopropil-4-fluorfenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– 2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il-N-(2,3,4-trifluorfenil)acetamidu
– N-[4-fluor-3-(trifluormetoksi)fenil]-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-[3-(2-hidroksietoksi)fenil]-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(3-jodfenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– metil-2-fluor-5-({[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetil}amino)benzoatu
– N-(3-etoksifenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(2,4-difluor-3-metoksifenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– 2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]-N-(2,4,5-trifluorfenil)acetamidu
– N-(3,5-diklor-4-fluorfenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– 2-[2-(2,3-dihidro-4H-1,4-benzoksazin-4-il)-2-oksoetil]-6-(morfolin-4-il)pirimidin-4(3H)-onu
– N-(4-fluor-3-nitrofenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– 2-fluor-5-({[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetil}amino)benzojevoj kiselini
– N-(5-fluor-2-hidroksifenil)-2-[4-morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(2-brom-4-fluorfenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(4-fluorfenil)-2-[1-metil-4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(3-klor-4-fluorfenil)-2-[1-metil-4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(3-bromfenil)-2-[1-metil-4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– 2-[1-etil-4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]-N-(4-fluorfenil)acetamidu
– N-(1H-indol-4-il)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(4-fluorfenil)-3-metil-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]butanamid
– N-[4-fluor-3-(metoksimetil)fenil]-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(4-fluor-3-jodfenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– 2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]-N-[3-(1,1,2,2-tetrafluoretoksi)fenil]acetamidu
– N-[3-(difluormetil)-4-fluorfenil]-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– 2,2-difluor-N-(4-fluorfenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(3,4-difluorfenil)-2-[1-metil-4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– 2-[2-(2,3-dihidro-1H-indol-1-il)-2-oksoetil]-3-metil-6-(morfolin-4-il)pirimidin-4(3H)-onu
– N-(3-brom-4-fluorfenil)-2-[1-metil-4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-[4-fluor-3-(hidroksimetil)fenil]-2-[1-metil-4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(3-ciklopropilfenil)-2-[1-metil-4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(4-fluor-3-metoksifenil)-2-[1-metil-4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(1-benzofur-4-il)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– 2-[1-metil-4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]-N-fenilacetamidu
– N-(3-ciklopropil-4-fluorfenil)-2-[1-metil-4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(3-fluor-2-hidroksifenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– 2-[2-(4-fluor-2,3-dihidro-1H-indol-1-il)-2-oksoetil]-6-(morfolin-4-il)pirimidin-4(3H)-onu
– 2-[2-(4-klor-2,3-dihidro-1H-indol-1-il)-2-oksoetil]-6-(morfolin-4-il)pirimidin-4(3H)-onu
– N-(3-etinil-4-fluorfenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– 2-[2-(4-hidroksi-2,3-dihidro-1H-indol-1-il)-2-oksoetil]-6-(morfolin-4-il)pirimidin-4(3H)-onu
– 2-[2-(4,6-difluor-2,3-dihidro-1H-indol-1-il)-2-oksoetil]-6-(morfolin-4-il)pirimidin-4(3H)-onu
– N-(4-fluor-3-jodfenil)-2-(1-metil-4-morfolin-4-il-6-okso-1,6-dihidropirimidin-2-il)acetamidu
– 2-[2-(4,5-difluor-2,3-dihidro-1H-indol-1-il)-2-oksoetil]-6-(morfolin-4-il)pirimidin-4(3H)-onu
– 2-[2-(6-fluor-2,3-dihidro-1H-indol-1-il)-2-oksoetil]-6-(morfolin-4-il)pirimidin-4(3H)-onu
– 2-[2-(2-metil-2,3-dihidro-1H-indol-1-il)-2-oksoetil]-6-(morfolin-4-il)pirimidin-4(3H)-onu
– N-[3-(difluormetil)-4-fluorfenil]-2-[1-metil-4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– 2-[1-metil-4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]-N-(3,4,5-trifluorfenil)acetamidu
– N-(1-metil-1H-indol-4-il)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– 2-[2-(4-metil-2,3-dihidro-1H-indol-1-il)-2-oksoetil]-6-(morfolin-4-il)pirimidin-4(3H)-onu
– 2-[2-(3-metil-2,3-dihidro-1H-indol-1-il)-2-oksoetil]-6-(morfolin-4-il)pirimidin-4(3H)-onu
– 2-[2-(4-fluor-2,3-dihidro-1H-indol-1-il)-2-oksoetil]-3-metil-6-(morfolin-4-il)pirimidin-4(3H)-onu
– 2-[2-(5-fluor-2,3-dihidroindol-1-il)-2-oksoetil]-6-morfolin-4-il-3H-pirimidin-4-onu
– 2-[2-(4-klor-2,3-dihidro-1H-indol-1-il)-2-oksoetil]-3-metil-6-(morfolin-4-il)pirimidin-4(3H)-onu
– N-(1-benzotiofen-4-il)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– 2-{2-[2-(hidroksimetil)-2,3-dihidro-1H-indol-1-il]-2-oksoetil}-6-(morfolin-4-il)pirimidin-4(3H)-onu
– 2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]-N-{2-[2-(piperidin-1-il)etoksi]fenil}acetamidu
– N-[2-(2-metoksietoksi)fenil]-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– 2-[2-(4-hidroksi-2,3-dihidro-1H-indol-1-il)-2-oksoetil]-3-metil-6-(morfolin-4-il)pirimidin-4(3H)-onu
– 2-[2-(4-metoksi-2,3-dihidro-1H-indol-1-il)-2-oksoetil]-3-metil-6-(morfolin-4-il)pirimidin-4(3H)-onu
– 2-[2-(3,4-dihidroizokinolin-2(1H)-il)-2-oksoetil]-6-(morfolin-4-il)pirimidin-4(3H)-onu
– 2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]-N-{2-[2-(pirolidin-1-il)etoksi]fenil}acetamidu
– 2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]-N-[2-(piridin-3-ilmetoksi)fenil]acetamidu
– 3-metil-2-[2-(4-metil-2,3-dihidro-1H-indol-1-il)-2-oksoetil]-6-(morfolin-4-il)pirimidin-4(3H)-onu
– 2-(2-{3-[(dimetilamino)metil]-2,3-dihidro-1H-indol-1-il}-2-oksoetil)-6-(morfolin-4-il)pirimidin-4(3H)-onu
– 2-[2-(4-brom-2,3-dihidro-1H-indol-1-il)-2-oksoetil]-3-metil-6-(morfolin-4-il)pirimidin-4(3H)-onu
– 2-{2-[(2S)-2-metil-2,3-dihidro-1H-indol-1-il]-2-oksoetil}-6-(morfolin-4-il)pirimidin-4(3H)-onu
– 2-{2-[(2R)-2-metil-2,3-dihidro-1H-indol-1-il]-2-oksoetil}-6-(morfolin-4-il)pirimidin-4(3H)-onu
– 3-metil-2-[2-(3-metil-2,3-dihidro-1H-indol-1-il)-2-oksoetil]-6-(morfolin-4-il)pirimidin-4(3H)-onu
– 2-{2-[2-(metoksimetil)-2,3-dihidro-1H-indol-1-il]-2-oksoetil}-6-(morfolin-4-il)pirimidin-4(3H)-onu
– 2-[2-(4-etoksi-2,3-dihidro-1H-indol-1-il)-2-oksoetil]-6-(morfolin-4-il)pirimidin-4(3H)-onu
– 1-{[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetil}-2,3-dihidro-1H-indol-2-karboksamid
– 3-metil-2-[2-(2-metil-2,3-dihidro-1H-indol-1-il)-2-oksoetil]-6-(morfolin-4-il)pirimidin-4(3H)-onu
– 2-[2-(6-fluor-2,3-dihidro-1H-indol-1-il)-2-oksoetil]-3-metil-6-(morfolin-4-il)pirimidin-4(3H)-onu
– 2-{2-[(3S)-3-metil-2,3-dihidro-1H-indol-1-il]-2-oksoetil}-6-(morfolin-4-il)pirimidin-4(3H)-onu
– 2-{2-[(3R)-3-metil-2,3-dihidro-1H-indol-1-il]-2-oksoetil}-6-(morfolin-4-il)pirimidin-4(3H)-onu
– 2-[2-(5,6-difluor-2,3-dihidro-1H-indol-1-il)-2-oksoetil]-3-metil-6-(morfolin-4-il)pirimidin-4(3H)-onu
– 2-[2-(4,5-difluor-2,3-dihidro-1H-indol-1-il)-2-oksoetil]-3-metil-6-(morfolin-4-il)pirimidin-4(3H)-onu
– 2-[2-(1,3-dihidro-2H-isoindol-2-il)-2-oksoetil]-6-(morfolin-4-il)pirimidin-4-(3H)-onu
– N-(1-benzotiofen-4-il)-2-[1-metil-4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– 2-[2-(5-klor-3,4-dihidrokinolin-1(2H)-il)-2-oksoetil]-6-morfolin-4-il)pirimidin-4(3H)-onu
– 2-{2-[4-(hidroksimetil)-2,3-dihidro-1H-indol-1-il]-2-oksoetil}-6-(morfolin-4-il)pirimidin-4(3H)-onu
– N-[4-fluor-2-(piperidin-4-ilmetoksi)fenil]-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– 2-[2-(5-klor-2,3-dihidroindol-1-il)-2-oksoetil]-6-morfolin-4-il-3H-pirimidin-4-onu
– 2-[2-(4-brom-2,3-dihidroindol-1-il)-2-oksoetil]-6-morfolin-4-il-3H-pirimidin-4-onu
– 2-(2-{(3S)-3-[(dimetilamino)metil]-2,3-dihidro-1H-indol-1-il}-2-oksoetil)-6-(morfolin-4-il)pirimidin-4(3H)-onu
– 2-(2-{(3R)-3-[(dimetilamino)metil]-2,3-dihidro-1H-indol-1-il}-2-oksoetil)-6-(morfolin-4-il)pirimidin-4(3H)-onu
– N-[4-fluor-2-(2-metoksietoksi)fenil]-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(1H-benzimidazol-4-il)-2-[4-(morfolin-4-il)-6-okso-1,6-diidroirimidin-2-il]acetamidu
– metil-2-hidroksi-3-({[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetil}amino)benzoatu
– 2-[2-(4-metoksi-2,3-dihidroindol-1-il)-2-oksoetil]-6-morfolin-4-il-3H-pirimidin-4-onu
– N-(3-brom-2-hidroksifenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(3,4-dihidro-2H-1,4-benzoksazin-8-il)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– metil-5-fluor-2-({[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetil}amino)benzoatu
– 2-(2-{3-[(dietilamino)metil]-2,3-dihidro-1H-indol-1-il}-2-oksoetil)-6-(morfolin-4-il)pirimidin-4(3H)-onu
– 2-[2-(2,3-dihidro-1H-pirolo[3,2-b]piridin-1-il)-2-oksoetil]-6-(morfolin-4-il)pirimidin-4(3H)-onu
– 2-[2-(5,6-difluor-2,3-dihidroindol-1-il)-2-oksoetil]-6-morfolin-4-il-3H-pirimidin-4-onu
– 2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]-N-[1,2,3,4-tetrahidrokinolin-8-il)acetamidu
– 2-[2-(8-klor-2,3-dihidro-4H-1,4-benzoksazin-4-il)-2-oksoetil]-6-(morfolin-4-il)pirimidin-4(3H)-onu
– N-(2-hidroksi-3-metilfenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(2-hidroksi-3-nitrofenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-(3-cijano-2-hidroksifenil)-2-[4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– N-[2-hidroksi-3-(trifluormetil)fenil]-2-4-(morfolin-4-il)-6-okso-1,6-dihidropirimidin-2-il]acetamidu
– 2-[2-(3,3-dimetil-2,3-dihidro-1H-indol-1-il)-2-oksoetil]-6-(morfolin-4-il)pirimidin-4(3H)-onu
a također i adicijskim solima navedenih produkata formule (I) s anorganskim i organskim kiselinama ili s anorganskim i organskim bazama.
4. Postupak priprave produkata formule (I) u skladu s bilo kojim od patentnih zahtjeva 1 do 3, naznačen time što se provodi prema shemi 1A, kao što je definirano niže:
Shema 1A:
[image]
gdje supstituent R1 ima značenja naznačena kao u bilo kojem od patentnih zahtjeva 1 i 2.
5. Postupak dobivanja produkata formule (I) u skladu s bilo kojim od patentnih zahtjeva 1 do 3, naznačen time što se provodi prema shemi 1B, kao što je definirano niže:
Shema 1B:
[image]
gdje supstituenti R1 i R5 imaju značenja naznačena kao u bilo kojem od patentnih zahtjeva 1 i 2.
6. Postupak dobivanja produkata formule (I) u skladu s bilo kojim od patentnih zahtjeva 1 do 3, naznačen time što se provodi prema shemi 1C, kao što je definirano niže:
Shema 1C:
[image]
gdje supstituenti R1, R2, R3 i R5 imaju značenja naznačena kao u bilo kojem od patentnih zahtjeva 1 i 2.
7. Produkti formule (I), u skladu s bilo kojim od patentnih zahtjeva 1 do 3, a također i farmaceutski prihvatljive adicijske soli navedenih produkata formule (I) s anorganskim i organskim kiseline ili s anorganskim i organskim bazama, naznačeni time što su namijenjeni upotrebi kao medikamenti.
8. Produkti formule (I), u skladu s patentnim zahtjevom 3, a također i farmaceutski prihvatljive adicijske soli navedenih produkata formule (I) s anorganskim i organskim kiselinama ili s anorganskim i organskim bazama, naznačeni time što su namijenjeni upotrebi kao medikamenti.
9. Farmaceutski pripravci, naznačeni time što sadrže, kao aktivni sastojak, najmanje jedan od produkata formule (I), u skladu s bilo kojim od patentnih zahtjeva 1 do 3, ili farmaceutski prihvatljivu sol ovog produkta, i farmaceutski prihvatljivu podlogu.
10. Produkti formule (I), u skladu s bilo kojim od patentnih zahtjeva 1 do 3, naznačeni time što su namijenjeni upotrebi u liječenju raka.
11. Produkti formule (I), u skladu s bilo kojim od patentnih zahtjeva 1 do 3, naznačeni time što su namijenjeni upotrebi u liječenju čvrstih ili tekućih tumora.
12. Produkti formule (I), u skladu s bilo kojim od patentnih zahtjeva 1 do 3, naznačeni time što su namijenjeni upotrebi u liječenju oblika raka otpornih na citotoksična sredstva.
13. Produkti formule (I), u skladu s bilo kojim od patentnih zahtjeva 1 do 3, naznačeni time što su namijenjeni upotrebi u liječenju primarnih tumora i/ili metastaza, osobito raka želuca, jetre, bubrega, jajnika, debelog crijeva, prostate, endometrija i pluća (NSCLC i SCLC), glioblastoma, raka štitnjače, mokraćnog mjehura i dojke, melanoma, limfoidnih ili mijeloidnih krvotvornih tumora, sarkoma, raka mozga, grkljana i limfnog sustava, raka kostiju i gušterače, te hamartoma.
14. Produkti formule (I), u skladu s bilo kojim od patentnih zahtjeva 1 do 3, naznačeni time što su namijenjeni upotrebi u kemoterapiji raka.
15. Produkti formule (I), u skladu s bilo kojim od patentnih zahtjeva 1 do 3, naznačeni time što su namijenjeni upotrebi u kemoterapiji raka, sami ili u kombinaciji.
16. Produkti formule (I), u skladu s bilo kojim od patentnih zahtjeva 1 do 3, naznačeni time što su inhibitori fosforilacije AKT (PKB).
17. Sintezni međuprodukti formula C, D, E i F, u skladu s patentnim zahtjevom 4, prikazani niže:
[image]
,
naznačen time što je R5 definiran kao u bilo kojem od patentnih zahtjeva 1 i 2.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0903239A FR2947547B1 (fr) | 2009-07-02 | 2009-07-02 | Nouveaux derives de (6-oxo-1,6-dihydro-pyrimidin-2-yl)-amide, leur preparation et leur utilisation pharmaceutique comme inhibiteurs de phosphorylation d'akt (pkb) |
| US24110009P | 2009-09-10 | 2009-09-10 | |
| FR0957070A FR2951169B1 (fr) | 2009-10-09 | 2009-10-09 | Nouveaux derives de (6-oxo-1,6-dihydro-pyrimidin-2-yl)-amide, leur preparation et leur utilisation pharmaceutique comme inhibiteurs de phosphorylation d'akt(pkb) |
| PCT/FR2010/051375 WO2011001114A1 (fr) | 2009-07-02 | 2010-07-01 | Nouveaux derives de (6-oxo-1,6-dihydro-pyrimidin-2-yl)-amide, leur preparation et leur utilisation pharmaceutique comme inhibiteurs de phosphorylation d'akt(pkb) |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20140478T1 true HRP20140478T1 (hr) | 2014-07-04 |
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| HRP20140478AT HRP20140478T1 (hr) | 2009-07-02 | 2014-05-28 | Novi derivati (6-okso-1,6-dihidropirimidin-2-il)amida, njihovo dobivanje, te farmaceutska upotreba kao inhibitora fosforilacije akt |
Country Status (37)
| Country | Link |
|---|---|
| US (2) | US8791255B2 (hr) |
| EP (1) | EP2448927B1 (hr) |
| JP (1) | JP5680638B2 (hr) |
| KR (1) | KR20120106714A (hr) |
| CN (1) | CN102548970B (hr) |
| AR (1) | AR077364A1 (hr) |
| AU (1) | AU2010267816B2 (hr) |
| CA (1) | CA2767064C (hr) |
| CL (1) | CL2012000003A1 (hr) |
| CO (1) | CO6480974A2 (hr) |
| CR (1) | CR20110703A (hr) |
| DK (1) | DK2448927T3 (hr) |
| DO (1) | DOP2011000407A (hr) |
| EA (1) | EA021088B1 (hr) |
| EC (1) | ECSP12011570A (hr) |
| ES (1) | ES2464125T3 (hr) |
| HK (1) | HK1169110A1 (hr) |
| HN (1) | HN2011003482A (hr) |
| HR (1) | HRP20140478T1 (hr) |
| IL (2) | IL217295A (hr) |
| MA (1) | MA33501B1 (hr) |
| ME (1) | ME01885B (hr) |
| MX (1) | MX2012000094A (hr) |
| MY (1) | MY153042A (hr) |
| NI (1) | NI201200002A (hr) |
| NZ (1) | NZ597579A (hr) |
| PE (1) | PE20120640A1 (hr) |
| PL (1) | PL2448927T3 (hr) |
| PT (1) | PT2448927E (hr) |
| RS (1) | RS53317B (hr) |
| SG (2) | SG177469A1 (hr) |
| SI (1) | SI2448927T1 (hr) |
| SM (1) | SMT201400084B (hr) |
| TW (1) | TWI466883B (hr) |
| UY (1) | UY32755A (hr) |
| WO (1) | WO2011001114A1 (hr) |
| ZA (1) | ZA201200026B (hr) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
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| FR2969609B1 (fr) * | 2010-12-28 | 2013-02-08 | Sanofi Aventis | Nouveaux derives de 6-oxo-dihydro-pyrimidine, leur preparation et leur utilisation pharmaceutique comme inhibiteurs de phosphorylation d'akt(pkb) |
| FR2969614A1 (fr) * | 2010-12-28 | 2012-06-29 | Sanofi Aventis | Nouveaux derives de pyrimidinones, leur preparation et leur utilisation pharmaceutique comme inhibiteurs de phosphorylation d'akt(pkb) |
| FR2969610B1 (fr) * | 2010-12-28 | 2013-04-05 | Sanofi Aventis | Nouveaux derives de (6-oxo-1,6-dihydro-pyrimidin-2-yl)-indolinamide, leur preparation et leur utilisation pharmaceutique comme inhibiteurs de phosphorylation d'akt(pkb) |
| HUE030393T2 (en) | 2010-12-28 | 2017-05-29 | Sanofi Sa | New pyrimidine derivatives, a process for their preparation, and their pharmaceutical use as inhibitors of AKT (PKB) phosphorylation |
| CN103476765A (zh) * | 2011-02-11 | 2013-12-25 | 达娜-法勃肿瘤研究所公司 | 抑制错构瘤肿瘤细胞的方法 |
| EP2570127A1 (en) * | 2011-09-16 | 2013-03-20 | Sanofi | Compositions and methods for treating cancer using PI3KB beta inhibitor and MAPK pathway inhibitor, including MEK and RAF inhibitors |
| CA2904770A1 (en) | 2013-03-15 | 2014-09-18 | Sanofi | Anti-tumoral composition comprising a pi3kbeta inhibitor and a raf inhibitor, to overcome cancer cells resistance |
| BR112015025101A2 (pt) | 2013-04-05 | 2017-07-18 | Sanofi Sa | composição antitumoral que compreende um inibidor pi3kbeta-seletivo e um inibidor pi3kalfa-seletivo |
| US10544902B2 (en) | 2014-12-02 | 2020-01-28 | Halliburton Energy Services, Inc. | Liquefied natural gas vaporizer for downhole oil or gas applications |
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| TWI241298B (en) * | 1998-09-25 | 2005-10-11 | Mitsubishi Chem Corp | Pyrimidone derivatives |
| MXPA02003436A (es) | 1999-10-07 | 2002-08-20 | Amgen Inc | Inhibidores de triazina cinasa. |
| NZ520300A (en) | 2000-01-24 | 2004-05-28 | Kinacia Pty Ltd | Morpholino-substituted pyridopyrimidine, quinolone and benzopyranone derivatives that inhibit the enzyme phosphoinositide (PI) 3-kinase |
| GB0119865D0 (en) | 2001-08-14 | 2001-10-10 | Cancer Res Campaign Tech | DNA-PK inhibitors |
| US7365069B2 (en) * | 2002-04-10 | 2008-04-29 | Bexel Pharmaceuticals Inc. | Pyrimidone derivatives |
| JP4646626B2 (ja) | 2002-08-16 | 2011-03-09 | アストラゼネカ アクチボラグ | ホスホイノシチド３−キナーゼβの阻害 |
| CA2543608A1 (en) * | 2003-10-31 | 2005-05-12 | Warner-Lambert Company Llc | Pyrimidines as inhibitors of phosphoinositide -3-kinases (pi3k) |
| GB0415365D0 (en) | 2004-07-09 | 2004-08-11 | Astrazeneca Ab | Pyrimidine derivatives |
| AR053358A1 (es) | 2005-04-15 | 2007-05-02 | Cancer Rec Tech Ltd | Inhibidores de adn - pk |
| EP1895997A2 (en) | 2005-05-26 | 2008-03-12 | Kudos Pharmaceuticals Ltd | Use of dna-pk inhibition to sensitise atm deficient cancers to dna-damaging cancer therapies |
| US7700592B2 (en) | 2005-08-25 | 2010-04-20 | Schering Corporation | α2C adrenoreceptor agonists |
| GB0520657D0 (en) | 2005-10-11 | 2005-11-16 | Ludwig Inst Cancer Res | Pharmaceutical compounds |
| US7745477B2 (en) | 2006-02-07 | 2010-06-29 | Hoffman-La Roche Inc. | Heteroaryl and benzyl amide compounds |
| WO2008064244A2 (en) | 2006-11-20 | 2008-05-29 | The Trustees Of Columbia University In The City Of New York | Phosphoinositide modulation for the treatment of neurodegenerative diseases |
| WO2008148074A2 (en) | 2007-05-24 | 2008-12-04 | Research Foundation Of State University Of New York | Inhibitors of mtor and methods of treatment using same |
| JP5508260B2 (ja) | 2007-07-09 | 2014-05-28 | アストラゼネカ アクチボラグ | ｍＴＯＲキナーゼおよび／またはＰ１３Ｋに関連する病気に用いられるモルホリノピリミジン誘導体 |
| KR20100031639A (ko) | 2007-07-09 | 2010-03-23 | 아스트라제네카 아베 | 증식성 질환의 치료용 삼중 치환된 피리미딘 유도체 |
| JP2010533161A (ja) | 2007-07-09 | 2010-10-21 | アストラゼネカ アクチボラグ | 化合物−９４６ |
| US20100261723A1 (en) * | 2007-07-09 | 2010-10-14 | Astrazeneca Ab | Trisubstituted pyrimidine derivatives for the treatment of proliferative diseases |
| AR074072A1 (es) | 2008-11-11 | 2010-12-22 | Lilly Co Eli | Compuesto de imidazol -piperidin -pirrol-pirimidin-6-ona, composicion farmaceutica que lo comprende y su uso para preparar un medicamento util para tratar el glioblastoma multiforme |
| US8283372B2 (en) | 2009-07-02 | 2012-10-09 | Tetralogic Pharmaceuticals Corp. | 2-(1H-indol-3-ylmethyl)-pyrrolidine dimer as a SMAC mimetic |
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