HRP20230458T1 - Piridazinoni kao inhibitori parp7 - Google Patents
Piridazinoni kao inhibitori parp7 Download PDFInfo
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- HRP20230458T1 HRP20230458T1 HRP20230458TT HRP20230458T HRP20230458T1 HR P20230458 T1 HRP20230458 T1 HR P20230458T1 HR P20230458T T HRP20230458T T HR P20230458TT HR P20230458 T HRP20230458 T HR P20230458T HR P20230458 T1 HRP20230458 T1 HR P20230458T1
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- Prior art keywords
- alkyl
- nrc3rd3
- aryl
- ora3
- optionally substituted
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- AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical class OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 title 1
- 239000003112 inhibitor Substances 0.000 title 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 59
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 53
- 150000001875 compounds Chemical class 0.000 claims 44
- 229910052736 halogen Inorganic materials 0.000 claims 41
- 150000002367 halogens Chemical class 0.000 claims 41
- 150000003839 salts Chemical class 0.000 claims 37
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims 36
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims 33
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 27
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 27
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 27
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 23
- 125000001424 substituent group Chemical group 0.000 claims 20
- 125000004432 carbon atom Chemical group C* 0.000 claims 19
- 101100310926 Caenorhabditis elegans sra-3 gene Proteins 0.000 claims 9
- 229910052799 carbon Inorganic materials 0.000 claims 8
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 7
- 125000000217 alkyl group Chemical group 0.000 claims 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 7
- 229910052760 oxygen Inorganic materials 0.000 claims 7
- 125000006713 (C5-C10) cycloalkyl group Chemical group 0.000 claims 6
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 5
- 101100310929 Caenorhabditis elegans sra-7 gene Proteins 0.000 claims 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 5
- 238000000634 powder X-ray diffraction Methods 0.000 claims 5
- 229910052717 sulfur Inorganic materials 0.000 claims 5
- 125000006568 (C4-C7) heterocycloalkyl group Chemical group 0.000 claims 4
- 102100038417 Cytoplasmic FMR1-interacting protein 1 Human genes 0.000 claims 4
- 101710181791 Cytoplasmic FMR1-interacting protein 1 Proteins 0.000 claims 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 4
- 125000004076 pyridyl group Chemical group 0.000 claims 4
- 206010028980 Neoplasm Diseases 0.000 claims 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 3
- 201000011510 cancer Diseases 0.000 claims 3
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 3
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims 3
- 125000002950 monocyclic group Chemical group 0.000 claims 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 3
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims 3
- 101100310920 Caenorhabditis elegans sra-2 gene Proteins 0.000 claims 2
- 206010009944 Colon cancer Diseases 0.000 claims 2
- 208000029742 colonic neoplasm Diseases 0.000 claims 2
- 238000000113 differential scanning calorimetry Methods 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- 125000004193 piperazinyl group Chemical group 0.000 claims 2
- 125000003367 polycyclic group Chemical group 0.000 claims 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims 2
- 238000001757 thermogravimetry curve Methods 0.000 claims 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims 1
- ZLEMCDYONYKKIC-YGONEPDPSA-N 5-[[(2S)-1-[3-oxo-3-[4-[5-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]propoxy]propan-2-yl]amino]-4-(trifluoromethyl)diazinan-3-one Chemical compound C[C@@H](COCCC(=O)N1CCN(CC1)C2=NC=C(C=N2)C(F)(F)F)NC3CNNC(=O)C3C(F)(F)F ZLEMCDYONYKKIC-YGONEPDPSA-N 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 206010014733 Endometrial cancer Diseases 0.000 claims 1
- 206010014759 Endometrial neoplasm Diseases 0.000 claims 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims 1
- 208000008839 Kidney Neoplasms Diseases 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 101100240985 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) nrc-2 gene Proteins 0.000 claims 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims 1
- 206010033128 Ovarian cancer Diseases 0.000 claims 1
- 206010061535 Ovarian 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
- 206010038389 Renal cancer Diseases 0.000 claims 1
- 101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 claims 1
- 208000006593 Urologic Neoplasms Diseases 0.000 claims 1
- 238000002441 X-ray diffraction Methods 0.000 claims 1
- 230000003187 abdominal effect Effects 0.000 claims 1
- 125000002947 alkylene group Chemical group 0.000 claims 1
- 201000007455 central nervous system cancer Diseases 0.000 claims 1
- 239000013078 crystal Substances 0.000 claims 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 201000004101 esophageal cancer Diseases 0.000 claims 1
- 201000010536 head and neck cancer Diseases 0.000 claims 1
- 208000014829 head and neck neoplasm Diseases 0.000 claims 1
- 125000001072 heteroaryl group Chemical group 0.000 claims 1
- 125000005842 heteroatom Chemical group 0.000 claims 1
- -1 hexahydropyrrolo[3,2-b]pyrrol-1(2H)-yl Chemical group 0.000 claims 1
- 201000010982 kidney cancer Diseases 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 208000020816 lung neoplasm Diseases 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 229910052757 nitrogen Inorganic materials 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
- 239000000843 powder Substances 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D401/14—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 three or more hetero 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
- A61K31/495—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
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/501—Pyridazines; Hydrogenated pyridazines not condensed and containing further 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
- A61K31/495—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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further 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
- A61K31/535—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
- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
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- 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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- 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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- C07D403/02—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
- C07D403/04—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 directly linked by a ring-member-to-ring-member bond
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- 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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- C07D405/14—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 three or more hetero rings
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- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
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- 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
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- 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
- C07D471/08—Bridged systems
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- 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
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- C07D487/08—Bridged systems
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Claims (39)
1. Spoj, naznačen time, da je predstavljen Formulom I:
[image]
ili njegova farmaceutski prihvatljiva sol, gdje:
X je Cl, Br, CH3, CF3, CN, OCH3, etil, ciklopropil, SCH3, ili izopropil;
A je skupina koja ima formulu (A-1):
[image]
svaki od Y1, Y2 i Y3 se neovisno bira od O, S, NRY, C(=O), C(=)O, C(=O)NRY, S(=O), S(=O)2, S(=O)NRY, S(=O)2NRY, ili NRYC(=O)NRY, gdje je svaki RY neovisno H ili C1-4 alkil;
L je C1-34 alkilen, O, S, NRY, C(=O), C(=O)O, C(=O)NRY, S(=O), S(=O)NRY, ili NRYC(=O)NRY;
Z je H, CyZ, halogen, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, CN, NO2, ORa, SRa, C(O)Rb, C(O)NRcRd, C(O)ORa, OC(O)Rb, OC(O)NRcRd, NRcRd, NRcC(O)Rb, NRcC(O)ORa, NRcC(O)NRcRd, C(=NRe)Rb, C(=NRe)NRcRd, NRcC(=NRe)NRcRd, NRcS(O)Rb,NRcS(O)2Rb, NRcS(O)2NRcRd, S(O)Rb, S(O)NRcRd, S(O)2Rb, i S(O)2NRcRd; gdje je svaki navedeni C1-6 alkil, C2-6 alkenil, C2-6 alkinil, i C1-6 haloalkil od Z, opcionalno supstituiran s 1, 2, 3, 4 ili 5 supstituenata koji su neovisno odabrani od CyZ, halogena, CN, NO2, ORa, SRa, C(O)Rb, C(O)NRcRd, C(O)ORa, OC(O)Rb, OC(O)NRcRd, C(=NRe)NRcRd, NRcC(=NRe)NRcRd, NRcRd, NRcC(O)Rb, NRcC(O)ORa, NRcC(O)NRcRd, NRcS(O)Rb,NRcS(O)2Rb, NRcS(O)2NRcRd, S(O)Rb, S(O)NRcRd, S(O)2Rb, i S(O)2NRcRd;
CyZ se bira od C6-10 aril, C3-7 cikloalkil, 5-10-člani heteroaril, i 4-10-člani heterocikloalkil, od kojih je svaki opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta neovisno odabrana od halogena, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(=NRe1)NRc1Rd1, NRc1C(=NRe1)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1,NRc1S(O)2Rb1, NRc1S(O)2NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, i S(O)2NRc1Rd1; gdje su alkil, C2-6 alkenil, i C2-6 alkinil, opcionalno supstituirani s 1, 2 ili 3 supstituenta koji su neovisno odabrani od halogena, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(=NRe1)NRc1Rd1, NRc1C(=NRe1)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1,NRc1S(O)2Rb1, NRc1S(O)2NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, i S(O)2NRc1Rd1;
Prsten D je monociklička ili policiklička 4-10-člana heterocikloalkil skupina koja je opcionalno supstituirana s 1, 2 ili 3 skupine neovisno odabrane od halogena, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, C(=NRe2)NRc2Rd2, NRc2C(=NRe2)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2,NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, i S(O)2NRc2Rd2; gdje je svaki C1-6 alkil, C2-6 alkenil, i C2-6 alkinil, opcionalno supstituiran s 1, 2 ili 3 skupine koje su neovisno odabrane od halogena, CN, NO2, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, C(=NRe2)NRc2Rd2, NRc2C(=NRe2)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2, NRc2S(O)Rb2,NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, i S(O)2NRc2Rd2;
svaki od R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11 i R12se neovisno bira od H, halogena, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C6-10 aril, C3-7 cikloalkil, 5-10-člani heteroaril, 4-10-člani heterocikloalkil, C6-10 aril-C1-4 alkil, C3-7 cikloalkil-C1-4 alkil, 5-10-člani heteroaril-C1-4 alkil, 4-10-člani heterocikloalkil-C1-4 alkil, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, C(=NRe3)Rb3, C(=NRe3)NRc3Rd3, NRc3C(=NRe3)NRc3Rd3, NRc3S(O)Rb3,NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, i S(O)2NRc3Rd3; gdje je svaki navedeni C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, C6-10 aril, C3-7 cikloalkil, 5-10-člani heteroaril, 4-10-člani heterocikloalkil, C6-10 aril-C1-4 alkil, C3-7 cikloalkil-C1-4 alkil, 5-10-člani heteroaril-C1-4 alkil, i 4-10-člani heterocikloalkil-C1-4 alkil od navedenih R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11 i R12, opcionalno supstituiran s 1, 2, 3, 4 ili 5 supstituenata koji su neovisno odabrani od halogena, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, C(=NRe3)Rb3, C(=NRe3)NRc3Rd3, NRc3C(=NRe3)NRc3Rd3, NRc3S(O)Rb3,NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, i S(O)2NRc3Rd3;
ili R1 i R3 zajedno s atomima ugljika s kojima su vezani, tvore C5-10 cikloalkil prsten ili 5-10-člani heterocikloalkil prsten, od kojih je svaki opcionalno supstituiran s 1, 2 ili 3 supstituenta neovisno odabrana od halogena, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, C(=NRe3)Rb3, C(=NRe3)NRc3Rd3, NRc3C(=NRe3)NRc3Rd3, NRc3S(O)Rb3,NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, i S(O)2NRc3Rd3;
ili R3 i R5 zajedno s atomima ugljika s kojima su vezani, tvore C5-10 cikloalkil prsten ili 5-10-člani heterocikloalkil prsten, od kojih je svaki opcionalno supstituiran s 1, 2 ili 3 supstituenta neovisno odabrana od halogena, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, C(=NRe3)Rb3, C(=NRe3)NRc3Rd3, NRc3C(=NRe3)NRc3Rd3, NRc3S(O)Rb3,NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, i S(O)2NRc3Rd3;
ili R7 i R9 zajedno s atomima ugljika s kojima su vezani, tvore C5-10 cikloalkil prsten ili 5-10-člani heterocikloalkil prsten, od kojih je svaki opcionalno supstituiran s 1, 2 ili 3 supstituenta neovisno odabrana od halogena, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, C(=NRe3)Rb3, C(=NRe3)NRc3Rd3, NRc3C(=NRe3)NRc3Rd3, NRc3S(O)Rb3,NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, i S(O)2NRc3Rd3;
ili R9 i R11 zajedno s atomima ugljika s kojima su vezani, tvore C5-10 cikloalkil prsten ili 5-10-člani heterocikloalkil prsten, od kojih je svaki opcionalno supstituiran s 1, 2 ili 3 supstituenta neovisno odabrana od halogena, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, C(=NRe3)Rb3, C(=NRe3)NRc3Rd3, NRc3C(=NRe3)NRc3Rd3, NRc3S(O)Rb3,NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, i S(O)2NRc3Rd3;
ili R5 i R7 zajedno s atomima ugljika s kojima su vezani i zajedno s Y2, tvore 5-10-člani heterocikloalkil prsten koji je opcionalno supstituiran s 1, 2 ili 3 supstituenta neovisno odabrana od halogena, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, C(=NRe3)Rb3, C(=NRe3)NRc3Rd3, NRc3C(=NRe3)NRc3Rd3, NRc3S(O)Rb3,NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, i S(O)2NRc3Rd3;
ili R1 i R3 zajedno tvore dvostruku vezu između atoma ugljika s kojima su vezani;
ili R3 i R5 zajedno tvore dvostruku vezu između atoma ugljika s kojima su vezani;
ili R7 i R9 zajedno tvore dvostruku vezu između atoma ugljika s kojima su vezani;
ili R9 i R11 zajedno tvore dvostruku vezu između atoma ugljika s kojima su vezani;
ili R9, R10, R11 i R12 zajedno tvore trostruku vezu između atoma ugljika s kojima su vezani;
svaki od Ra, Rb, Rc, Rd, Ra1, Rb1, Rc1, Rd1, Ra2, Rb2, Rc2, Rd2, Ra3, Rb3, Rc3 i Rd3 se neovisno bira od H, C1-6 alkil, C1-6 haloalkil, C2-6 alkenil, C2-6 alkinil, C6-10 aril, C3-7 cikloalkil, 5-10-člani heteroaril, 4-10-člani heterocikloalkil, C6-10 aril-C1-4 alkil, C3-7 cikloalkil-C1-4 alkil, 5-10-člani heteroaril-C1-4 alkil, i 4-10-člani heterocikloalkil-C1-4 alkil, gdje je svaki navedeni C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C6-10 aril, C3-7 cikloalkil, 5-10-člani heteroaril, 4-10-člani heterocikloalkil, C6-10 aril-C1-4 alkil, C3-7 cikloalkil-C1-4 alkil, 5-10-člani heteroaril-C1-4 alkil, i 4-10-člani heterocikloalkil-C1-4 alkil od navedenih Ra, Rb, Rc, Rd, Ra1, Rb1, Rc1, Rd1, Ra2, Rb2, Rc2, Rd2, Ra3, Rb3, Rc3 i Rd3, opcionalno supstituiran s 1, 2 ili 3 supstituenta koji su neovisno odabrani od halogena, C1-4 alkil, C1-4 haloalkil, C2-6 alkenil, C2-6 alkinil, CN, ORa7, SRa7, C(O)Rb7, C(O)NRc7Rd7, C(O)ORa7, OC(O)Rb7, OC(O)NRc7Rd7, NRc7Rd7, NRc7C(O)Rb7, NRc7C(O)NRc7Rd7, NRc7C(O)ORa7, C(=NRe7)NRc7Rd7, NRc7C(=NRe7)NRc7Rd7, S(O)Rb7, S(O)NRc7Rd7, S(O)2Rb7, NRc7S(O)2Rb7, NRc7S(O)2NRc7Rd7, i S(O)2NRc7Rd7;
ili Rc i Rd zajedno s N atomom s kojim su vezani, tvore 4-7-članu heterocikloalkil skupinu opcionalno supstituiranu s 1, 2 ili 3 supstituenta neovisno odabrana od CN, halogena, C1-4 alkil, C1-4 haloalkil, C1-6 haloalkil, C2-6 alkenil, C2-6 alkinil, CN, NO2, ORa7, SRa7, C(O)Rb7, C(O)NRc7Rd7, C(O)ORa7, OC(O)Rb7, OC(O)NRc7Rd7, NRc7Rd7, NRc7C(O)Rb7, NRc7C(O)NRc7Rd7, NRc7C(O)ORa7, C(=NRe7)NRc7Rd7, NRc7C(=NRe7)NRc7Rd7, S(O)Rb7, S(O)NRc7Rd7, S(O)2Rb7, NRc7S(O)2Rb7, NRc7S(O)2NRc7Rd7, i S(O)2NRc7Rd7;
ili Rc1 i Rd1 zajedno s N atomom s kojim su vezani, tvore 4-7-članu heterocikloalkil skupinu koja je opcionalno supstituirana s 1, 2 ili 3 supstituenta neovisno odabrana od CN, halogena, C1-4 alkil, C1-4 haloalkil, C1-6 haloalkil, C2-6 alkenil, C2-6 alkinil, CN, ORa7, SRa7, C(O)Rb7, C(O)NRc7Rd7, C(O)ORa7, OC(O)Rb7, OC(O)NRc7Rd7, NRc7Rd7, NRc7C(O)Rb7, NRc7C(O)NRc7Rd7, NRc7C(O)ORa7, C(=NRe7)NRc7Rd7, NRc7C(=NRe7)NRc7Rd7, S(O)Rb7, S(O)NRc7Rd7, S(O)2Rb7, NRc7S(O)2Rb7, NRc7S(O)2NRc7Rd7, i S(O)2NRc7Rd7;
ili Rc2 i Rd2 zajedno s N atomom s kojim su vezani, tvore 4-7-članu heterocikloalkil skupinu koja je opcionalno supstituirana s 1, 2 ili 3 supstituenta neovisno odabrana od CN, halogena, C1-4 alkil, C1-4 haloalkil, C1-6 haloalkil, C2-6 alkenil, C2-6 alkinil, CN, ORa7, SRa7, C(O)Rb7, C(O)NRc7Rd7, C(O)ORa7, OC(O)Rb7, OC(O)NRc7Rd7, NRc7Rd7, NRc7C(O)Rb7, NRc7C(O)NRc7Rd7, NRc7C(O)ORa7, C(=NRe7)NRc7Rd7, NRc7C(=NRe7)NRc7Rd7, S(O)Rb7, S(O)NRc7Rd7, S(O)2Rb7, NRc7S(O)2Rb7, NRc7S(O)2NRc7Rd7, i S(O)2NRc7Rd7;
ili Rc3 i Rd3 zajedno s N atomom s kojim su vezani, tvore 4-7-članu heterocikloalkil skupinu koja je opcionalno supstituirana s 1, 2 ili 3 supstituenta neovisno odabrana od CN, halogena, C1-4 alkil, C1-4 haloalkil, C1-6 haloalkil, C2-6 alkenil, C2-6 alkinil, CN, ORa7, SRa7, C(O)Rb7, C(O)NRc7Rd7, C(O)ORa7, OC(O)Rb7, OC(O)NRc7Rd7, NRc7Rd7, NRc7C(O)Rb7, NRc7C(O)NRc7Rd7, NRc7C(O)ORa7, C(=NRe7)NRc7Rd7, NRc7C(=NRe7)NRc7Rd7, S(O)Rb7, S(O)NRc7Rd7, S(O)2Rb7, NRc7S(O)2Rb7, NRc7S(O)2NRc7Rd7, i S(O)2NRc7Rd7;
Ra7, Rb7, Rc7 i Rd7 se neovisno biraju od H, C1-6 alkil, C1-6 haloalkil, C2-6 alkenil, C2-6 alkinil, C6-10 aril, C3-7 cikloalkil, 5-10-člani heteroaril, 4-10-člani heterocikloalkil, C6-10 aril-C1-4 alkil, C3-7 cikloalkil-C1-4 alkil, 5-10-člani heteroaril-C1-4 alkil, i 4-10-člani heterocikloalkil-C1-4 alkil; gdje je svaki navedeni C1-6 alkil, C1-6 haloalkil, C2-6 alkenil, C2-6 alkinil, C6-10 aril, C3-7 cikloalkil, 5-10-člani heteroaril, 4-10-člani heterocikloalkil, C6-10 aril-C1-4 alkil, C3-7 cikloalkil-C1-4 alkil, 5-10-člani heteroaril-C1-4 alkil, i 4-10-člani heterocikloalkil-C1-4 alkil, opcionalno supstituiran s 1, 2 ili 3 supstituenta neovisno odabrana od OH, CN, amino, halogena, C1-6 alkil, C1-6 alkoksi, C1-6 haloalkil, i C1-6 haloalkoksi;
svaki Re, Re1, Re2, Re3 i Re7 se neovisno bira od H, C1-4 alkil, i CN;
a je 0 ili 1;
m je 0 ili 1;
n je 0 ili 1;
p je 0 ili 1;
q je 0 ili 1;
r je 0 ili 1;
pri čemu bilo koja gore navedena heteroaril ili heterocikloalkil skupina sadrži 1, 2, 3 ili 4 heteroatoma koji tvore prsten i koji se neovisno biraju od O, N i S; i
pri čemu je jedan ili više C i N atoma koji tvore prsten iz bilo koje od gore navedenih heterocikloalkil skupina, opcionalno supstituiran s okso (=O) skupinom.
2. Spoj prema patentnom zahtjevu 1, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
a) A je skupina koja ima formulu (A-1a):
[image]
ili
b) A je skupina koja ima formulu (A-1b):
[image]
ili
c) A je skupina koja ima formulu (A-1c):
[image]
u kojoj se svaki Z1 i Z2 neovisno bira od N i CH, i pritom R je CN, Cl ili CF3; ili
d) A je skupina koja ima formulu (A-1d):
[image]
u kojoj se svaki Z1 i Z2 neovisno bira od N i CH, i pritom R je CN, Cl ili CF3.
3. Spoj prema patentnom zahtjevu 1, ili njegova farmaceutski prihvatljiva sol, naznačen time, da L je NRY ili O.
4. Spoj prema bilo kojem od patentnih zahtjeva 1-3, ili njegova farmaceutski prihvatljiva sol, naznačen time, da X je CF3, CH3, CN, Cl ili Br.
5. Spoj prema bilo kojem od patentnih zahtjeva 1-4, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
a) Y1 je NRY ili O; ili
b) Y1 je NRY, O ili S; ili
c) Y1 je NRY; ili
d) Y1 je O.
6. Spoj prema bilo kojem od patentnih zahtjeva 1-5, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
a) Y2 je NRY ili O; ili
b) Y2 je NRY, O ili S; ili
c) Y2 je O.
7. Spoj prema bilo kojem od patentnih zahtjeva 1-6, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
a) Y3 je C(=O); ili
b) Y3 je C(=O) ili S(=O)2.
8. Spoj prema bilo kojem od patentnih zahtjeva 1-7, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
a) RY je H ili C1-4 alkil; ili
b) RY je metil; ili
c) RY je H.
9. Spoj prema bilo kojem od patentnih zahtjeva 1-8, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
a) Z je H, CyZ, halogen, C1-6 alkil, C1-6 haloalkil, CN, NO2, ORa, C(O)Rb, C(O)NRcRd, C(O)ORa, NRcRd, i NRcC(O)Rb; pri čemu je svaki navedeni C1-6 alkil, i C1-6 haloalkil od Z, opcionalno supstituiran s 1, 2, 3, 4 ili 5 supstituenata koji su neovisno odabrani od CyZ, halogena, CN, NO2, ORa, SRa, C(O)Rb, C(O)NRcRd, C(O)ORa, OC(O)Rb, OC(O)NRcRd, NRcRd, i NRcC(O)Rb; ili
b) Z je CyZ.
10. Spoj prema bilo kojem od patentnih zahtjeva 1-9, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
a) CyZ se bira od 5-10-članog heteroarila i 4-10-članog heterocikloalkila, od kojih je svaki opcionalno supstituiran s 1, 2, 3 ili 4 supstituenta neovisno odabrana od halogena, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(=NRe1)NRc1Rd1, NRc1C(=NRe1)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1,NRc1S(O)2Rb1, NRc1S(O)2NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, i S(O)2NRc1Rd1; gdje su alkil, C2-6 alkenil, i C2-6 alkinil, opcionalno supstituirani s 1, 2 ili 3 supstituenta neovisno odabrana od halogena, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, C(=NRe1)NRc1Rd1, NRc1C(=NRe1)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1,NRc1S(O)2Rb1, NRc1S(O)2NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1, i S(O)2NRc1Rd1; ili
b) CyZ je 5-10-člani heteroaril, opcionalno supstituiran sa CN, CF3 ili Cl; ili
c) CyZ je 5-10-člani heteroaril, opcionalno supstituiran sa CN, C1-6 alkil, C1-6 haloalkil, halogen, ili NRc1Rd1, gdje je C1-6 alkil, opcionalno supstituiran sa CN, ili NRc1Rd1; ili
d) CyZ je piridinil ili pirimidinil, od kojih je svaki opcionalno supstituiran sa CN, CF3, ili Cl.
11. Spoj prema bilo kojem od patentnih zahtjeva 1-10, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
a) Prsten D je monociklička ili policiklička 4-10-člana heterocikloalkil skupina koja je opcionalno supstituirana s 1, 2 ili 3 skupine neovisno odabrane od halogena, C1-6 alkil, C1-6 haloalkil, CN, NO2, ORa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, NRc2Rd2, NRc2C(O)Rb2, gdje je C1-6 alkil opcionalno supstituiran s 1, 2 ili 3 skupine neovisno odabrane od halogena, CN, NO2, ORa2, C(O)Rb2, NRc2Rd2, i NRc2C(O)Rb2; ili
b) Prsten D je monociklička 4-10-člana heterocikloalkil skupina; ili
c) Prsten D je piperazinil; ili
d) Prsten D je piperazinil, dihidropiridazinil, diazepail, pirolidinil, ili heksahidropirolo[3,2-b]pirol-1(2H)-il.
12. Spoj prema bilo kojem od patentnih zahtjeva 1-11, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
a) R1 je H, halogen, ORa3, C1-6 alkil, C6-10 aril, 5-10-člani heteroaril, C6-10 aril-C1-4 alkil, gdje je navedeni C1-6 alkil, C6-10 aril, 5-10-člani heteroaril, ili C6-10 aril-C1-4 alkil, opcionalno supstituiran s ORa3, ili NRc3Rd3;
ili
b) R1 je H, halogen, ORa3, C1-6 alkil, C6-10 aril, 5-10-člani heteroaril, 4-10-člani heterocikloalkil, C6-10 aril-C1-4 alkil, 5-10-člani heteroaril-C1-4 alkil, ili 4-10-člani heterocikloalkil-C1-4 alkil, gdje je navedeni C1-6 alkil, C6-10 aril, 5-10-člani heteroaril, C6-10 aril-C1-4 alkil, 5-10-člani heteroaril-C1-4 alkil, ili 4-10-člani heterocikloalkil-C1-4 alkil, opcionalno supstituiran s ORa3, ili NRc3Rd3; ili
c) R1 je C1-6 alkil; ili
d) R1 je C1-6 alkil, opcionalno supstituiran s ORa3; ili
e) R1 je H; ili
f) R1 je metil, etil, ili izopropil; ili
g) R1 je metoksimetil, ili hidroksimetil; ili
h) R1 je fenil, fenilmetil, ili piridinil.
13. Spoj prema bilo kojem od patentnih zahtjeva 1-12, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
a) R2 je H, halogen, ORa3, C1-6 alkil, C6-10 aril, 5-10-člani heteroaril, C6-10 aril-C1-4 alkil, gdje je navedeni C1-6 alkil, C6-10 aril, 5-10-člani heteroaril, ili C6-10 aril-C1-4 alkil, opcionalno supstituiran s ORa3 ili NRc3Rd3; ili
b) R2 je ORa3; ili
c) R2 je H.
14. Spoj prema bilo kojem od patentnih zahtjeva 1-13, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
a) R3 je H, halogen, ORa3, C1-6 alkil, C6-10 aril, 5-10-člani heteroaril, C6-10 aril-C1-4 alkil, gdje je navedeni C1-6 alkil, C6-10 aril, 5-10-člani heteroaril, ili C6-10 aril-C1-4 alkil, opcionalno supstituiran s ORa3, ili NRc3Rd3;
ili
b) R3 je H; ili
c) R3 je metil, etil, ili izopropil; ili
d) R3 je metoksimetil, ili hidroksimetil; ili
e) R3 je fenil, fenilmetil, ili piridinil.
15. Spoj prema bilo kojem od patentnih zahtjeva 1-14, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
a) R4 je H, halogen, ORa3, C1-6 alkil, C6-10 aril, 5-10-člani heteroaril, C6-10 aril-C1-4 alkil, gdje je navedeni C1-6 alkil, C6-10 aril, 5-10-člani heteroaril, ili C6-10 aril-C1-4 alkil, opcionalno supstituiran s ORa3, ili NRc3Rd3;
ili
b) R4 je H.
16. Spoj prema bilo kojem od patentnih zahtjeva 1-15, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
a) R5 je H, halogen, ORa3, C1-6 alkil, C6-10 aril, 5-10-člani heteroaril, C6-10 aril-C1-4 alkil, gdje je navedeni C1-6 alkil, C6-10 aril, 5-10-člani heteroaril, ili C6-10 aril-C1-4 alkil, opcionalno supstituiran s ORa3, ili NRc3Rd3;
ili
b) R5 je H; ili
c) R5 je metil, etil, ili izopropil; ili
d) R5 je metoksimetil, ili hidroksimetil; ili
e) R5 je fenil, fenilmetil, ili piridinil.
17. Spoj prema bilo kojem od patentnih zahtjeva 1-16, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
a) R6 je H, halogen, ORa3, C1-6 alkil, C6-10 aril, 5-10-člani heteroaril, C6-10 aril-C1-4 alkil, gdje je navedeni C1-6 alkil, C6-10 aril, 5-10-člani heteroaril, ili C6-10 aril-C1-4 alkil, opcionalno supstituiran s ORa3, ili NRc3Rd3;
ili
b) R6 je H.
18. Spoj prema bilo kojem od patentnih zahtjeva 1-17, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
a) R7 je H, halogen, ORa3, C1-6 alkil, C6-10 aril, 5-10-člani heteroaril, C6-10 aril-C1-4 alkil, gdje je navedeni C1-6 alkil, C6-10 aril, 5-10-člani heteroaril, ili C6-10 aril-C1-4 alkil, opcionalno supstituiran s ORa3, ili NRc3Rd3;
ili
b) R7 je C1-6 alkil; ili
c) R7 je metil.
19. Spoj prema bilo kojem od patentnih zahtjeva 1-18, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
a) R8 je H, halogen, ORa3, C1-6 alkil, C6-10 aril, 5-10-člani heteroaril, ili C6-10 aril-C1-4 alkil, gdje je navedeni C1-6 alkil, C6-10 aril, 5-10-člani heteroaril, ili C6-10 aril-C1-4 alkil, opcionalno supstituiran s ORa3, ili NRc3Rd3;
ili
b) R8 je H.
20. Spoj prema bilo kojem od patentnih zahtjeva 1-19, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
a) R9 je H, halogen, ORa3, C1-6 alkil, C6-10 aril, 5-10-člani heteroaril, ili C6-10 aril-C1-4 alkil, gdje je navedeni C1-6 alkil, C6-10 aril, 5-10-člani heteroaril, ili C6-10 aril-C1-4 alkil, opcionalno supstituiran s ORa3 ili NRc3Rd3;
ili
b) R9 je H.
21. Spoj prema bilo kojem od patentnih zahtjeva 1-20, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
a) R10 je H, halogen, ORa3, C1-6 alkil, C6-10 aril, 5-10-člani heteroaril, C6-10 aril-C1-4 alkil, gdje je navedeni C1-6 alkil, C6-10 aril, 5-10-člani heteroaril, ili C6-10 aril-C1-4 alkil, opcionalno supstituiran s ORa3, ili NRc3Rd3;
ili
b) R10 je H.
22. Spoj prema bilo kojem od patentnih zahtjeva 1-21, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
a) R11 je H, halogen, ORa3, C1-6 alkil, C6-10 aril, 5-10-člani heteroaril, ili C6-10 aril-C1-4 alkil, gdje je navedeni C1-6 alkil, C6-10 aril, 5-10-člani heteroaril, ili C6-10 aril-C1-4 alkil, opcionalno supstituiran s ORa3 ili NRc3Rd3;
ili
b) R11 je H.
23. Spoj prema bilo kojem od patentnih zahtjeva 1-22, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
a) R12 je H, halogen, ORa3, C1-6 alkil, C6-10 aril, 5-10-člani heteroaril, ili C6-10 aril-C1-4 alkil, gdje je navedeni C1-6 alkil, C6-10 aril, 5-10-člani heteroaril, ili C6-10 aril-C1-4 alkil, opcionalno supstituiran s ORa3 ili NRc3Rd3;
ili
b) R12 je H.
24. Spoj prema bilo kojem od patentnih zahtjeva 1-13, 15, i 17-23, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
a) R3 i R5 zajedno s atomima ugljika s kojima su vezani, tvore C5-10 cikloalkil prsten, ili 5-10-člani heterocikloalkil prsten, od kojih je svaki opcionalno supstituiran s 1, 2 ili 3 supstituenta neovisno odabrana od halogena, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, C(=NRe3)Rb3, C(=NRe3)NRc3Rd3, NRc3C(=NRe3)NRc3Rd3, NRc3S(O)Rb3,NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, i S(O)2NRc3Rd3; ili
b) R3 i R5 zajedno s atomima ugljika s kojima su vezani, tvore C5-10 cikloalkil prsten, ili 5-10-člani heterocikloalkil prsten; ili
c) R3 i R5 zajedno s atomima ugljika s kojima su vezani, tvore tetrahidrofuranil prsten; ili
d) R3 i R5 zajedno s atomima ugljika s kojima su vezani, tvore ciklobutil ili ciklopentil prsten.
25. Spoj prema bilo kojem od patentnih zahtjeva 1-15, 17, i 19-24, ili njegova farmaceutski prihvatljiva sol, naznačen time, da:
a) R5 i R7 zajedno s atomima ugljika s kojima su vezani, i zajedno s Y2, tvore 5-10-člani heterocikloalkil prsten koji je opcionalno supstituiran s 1, 2 ili 3 supstituenta neovisno odabrana od halogena, C1-6 alkil, C2-6 alkenil, C2-6 alkinil, C1-6 haloalkil, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3, C(=NRe3)Rb3, C(=NRe3)NRc3Rd3, NRc3C(=NRe3)NRc3Rd3, NRc3S(O)Rb3,NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, i S(O)2NRc3Rd3; ili
b) R5 i R7 zajedno s atomima ugljika s kojima su vezani, i zajedno s Y2, tvore 5-10-člani heterocikloalkil prsten; ili
c) R5 i R7 zajedno s atomima ugljika s kojima su vezani, i zajedno s Y2, tvore tetrahidrofuranil prsten, ili tetrahidropiranil prsten; ili
d) R5 i R7 zajedno s atomima ugljika s kojima su vezani, i zajedno s Y2, tvore tetrahidrofuranil prsten, tetrahidropiranil prsten, ili pirolidinil prsten.
26. Spoj prema bilo kojem od patentnih zahtjeva 1 i 3-25, ili njegova farmaceutski prihvatljiva sol, naznačen time, da m je 1.
27. Spoj prema bilo kojem od patentnih zahtjeva 1 i 3-26, ili njegova farmaceutski prihvatljiva sol, naznačen time, da n je 0.
28. Spoj prema bilo kojem od patentnih zahtjeva 1 i 3-27, ili njegova farmaceutski prihvatljiva sol, naznačen time, da p je 1.
29. Spoj prema bilo kojem od patentnih zahtjeva 1 i 3-28, ili njegova farmaceutski prihvatljiva sol, naznačen time, da q je 0.
30. Spoj prema bilo kojem od patentnih zahtjeva 1 i 3-29, ili njegova farmaceutski prihvatljiva sol, naznačen time, da r je 1.
31. Spoj prema bilo kojem od patentnih zahtjeva 1 i 3-30, ili njegova farmaceutski prihvatljiva sol, naznačen time, da a je 0.
32. Spoj prema bilo kojem od patentnih zahtjeva 1-2, i 4-25, ili njegova farmaceutski prihvatljiva sol, naznačen time, da je predstavljen:
a) Formulom IIa:
[image]
ili
b) Formulom IIb:
[image]
ili
c) Formulom IIc:
[image]
u kojoj se svaki Z1 i Z2 neovisno bira od N i CH, i gdje R je CN, Cl, ili CF3; ili
d) Formulom IId:
[image]
u kojoj se svaki Z1 i Z2 neovisno bira od N i CH, i gdje R je CN, Cl, ili CF3.
33. Spoj prema patentnom zahtjevu 1, naznačen time, da spoj je 5-[[(2S)-1-(3-okso-3-[4-[5-(trifluorometil)pirimidin-2-il]piperazin-1-il]propoksi)propan-2-il]amino]-4-(trifluorometil)-2,3-dihidropiridazin-3-on, ili njegova farmaceutski prihvatljiva sol.
34. Spoj prema patentnom zahtjevu 33, naznačen time, da spoj je kristal.
35. Spoj prema patentnom zahtjevu 33 ili 34, naznačen time, da spoj posjeduje:
a) najmanje jedan karakteristični maksimum XRPD rendgenske difrakcije na prahu, odabran od oko 5,8, oko 10,8, oko 11,9, i oko 17,2 stupnjeva 2-theta; ili
b) najmanje jedan karakteristični maksimum XRPD rendgenske difrakcije na prahu, odabran od oko 5,8, oko 10,8, oko 11,9, oko 13,3, oko 13,5, oko 15,5, i oko 17,2 stupnjeva 2-theta; ili
c) uzorak XRPD rendgenske difrakcije na prahu s karakterističnim maksimumima kao što je u bitnom prikazano na Slici 8.
36. Spoj prema bilo kojem od patentnih zahtjeva 33-35, naznačen time, da spoj posjeduje:
a) termogram DSC diferencijalne skenirajuće kalorimetrije, naznačen time, da ima endotermički maksimum na temperaturi od oko 174 °C; ili
b) termogram DSC diferencijalne skenirajuće kalorimetrije koji je u bitnom opisan na Slici 9.
37. Farmaceutski pripravak, naznačen time, da sadrži spoj prema bilo kojem od patentnih zahtjeva 1-36, ili njegovu farmaceutski prihvatljivu sol, i najmanje jedan farmaceutski prihvatljiv nosač.
38. Spoj prema bilo kojem od patentnih zahtjeva 1-36, ili njegova farmaceutski prihvatljiva sol, naznačen time, da je za uporabu u postupku liječenja raka kod pacijenta kojemu je potrebno liječenje, pri čemu postupak obuhvaća davanje navedenom pacijentu terapijski učinkovite količine spoja, ili njegove farmaceutski prihvatljive soli.
39. Spoj ili njegova farmaceutski prihvatljiva sol, za uporabu prema patentnom zahtjevu 38, naznačen time, da navedeni rak je rak dojke, rak središnjeg živčanog sustava, rak endometrija, rak bubrega, rak velikog crijeva, rak pluća, rak jednjaka, rak jajnika, rak gušterače, rak prostate, rak abdomena, rak glave i vrata (gornjeg aerodigestivnog centra), rak urinarnog trakta, ili rak debelog crijeva.
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| MA52486B1 (fr) * | 2018-04-30 | 2023-04-28 | Ribon Therapeutics Inc | Pyridazinones utilisés en tant qu'inhibiteurs de parp7 |
| WO2019212946A1 (en) | 2018-04-30 | 2019-11-07 | Ribon Therapeutics Inc. | Screening methods for parp modulators |
| WO2019241131A1 (en) | 2018-06-11 | 2019-12-19 | Pipeline Therapeutics, Inc. | Muscarinic acetylcholine m1 receptor antagonists |
| WO2020223229A1 (en) * | 2019-04-29 | 2020-11-05 | Ribon Therapeutics, Inc. | Solid forms of a parp7 inhibitor |
| CN114729044A (zh) * | 2019-10-07 | 2022-07-08 | 帕珀莱恩医疗公司 | 毒蕈碱型乙酰胆碱m1受体拮抗剂 |
| AR120338A1 (es) * | 2019-10-30 | 2022-02-09 | Ribon Therapeutics Inc | Piridazinonas como inhibidores de parp7 |
| WO2021087018A1 (en) * | 2019-10-30 | 2021-05-06 | Ribon Therapeutics, Inc. | Pyridazinones as parp7 inhibitors |
| US11752149B2 (en) | 2019-12-02 | 2023-09-12 | Pipeline Therapeutics, Inc. | Muscarinic acetylcholine M1 receptor antagonists |
| AU2021287462A1 (en) * | 2020-06-09 | 2023-02-09 | Relive Therapeutics Inc. | Compounds comprising a three ring core as PD-1/PD-L1 blockers |
| CA3184594A1 (en) * | 2020-07-03 | 2022-01-06 | Jinping LI | Heterocyclic compound and use thereof |
| CN116157396A (zh) * | 2020-11-27 | 2023-05-23 | 成都百裕制药股份有限公司 | 哒嗪酮衍生物及其在医药上的应用 |
| WO2022156708A1 (en) * | 2021-01-20 | 2022-07-28 | Jacobio Pharmaceuticals Co., Ltd. | Parp7 enzyme inhibitor |
| CN116724044A (zh) * | 2021-02-03 | 2023-09-08 | 上海湃隆生物科技有限公司 | 三并杂环类化合物、其制备方法及其应用 |
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