MX2014013751A - Piridazina y derivados de piridina como inhibidores de nampt. - Google Patents
Piridazina y derivados de piridina como inhibidores de nampt.Info
- Publication number
- MX2014013751A MX2014013751A MX2014013751A MX2014013751A MX2014013751A MX 2014013751 A MX2014013751 A MX 2014013751A MX 2014013751 A MX2014013751 A MX 2014013751A MX 2014013751 A MX2014013751 A MX 2014013751A MX 2014013751 A MX2014013751 A MX 2014013751A
- Authority
- MX
- Mexico
- Prior art keywords
- carboxamide
- phenyl
- pyridazin
- azetidine
- piperidin
- Prior art date
Links
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 title claims description 5
- 108010064862 Nicotinamide phosphoribosyltransferase Proteins 0.000 title abstract description 21
- 102100033223 Nicotinamide phosphoribosyltransferase Human genes 0.000 title description 19
- 239000003112 inhibitor Substances 0.000 title description 12
- 150000003222 pyridines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 69
- 150000003839 salts Chemical class 0.000 claims abstract description 38
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 20
- 201000010099 disease Diseases 0.000 claims abstract description 15
- 238000000034 method Methods 0.000 claims abstract description 15
- 239000000203 mixture Substances 0.000 claims abstract description 9
- -1 heterocylyl Chemical group 0.000 claims description 1406
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 1242
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 800
- XCUAIINAJCDIPM-XVFCMESISA-N N(4)-hydroxycytidine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=NO)C=C1 XCUAIINAJCDIPM-XVFCMESISA-N 0.000 claims description 321
- 229910003204 NH2 Inorganic materials 0.000 claims description 250
- 125000000217 alkyl group Chemical group 0.000 claims description 248
- VALZSZJVEFACEZ-UHFFFAOYSA-N azetidine-3-carboxamide Chemical compound NC(=O)C1CNC1 VALZSZJVEFACEZ-UHFFFAOYSA-N 0.000 claims description 238
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 224
- 125000003118 aryl group Chemical group 0.000 claims description 161
- 125000001424 substituent group Chemical group 0.000 claims description 153
- 125000003342 alkenyl group Chemical group 0.000 claims description 137
- 229910052739 hydrogen Inorganic materials 0.000 claims description 109
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 108
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 106
- 229910052731 fluorine Inorganic materials 0.000 claims description 104
- 125000000623 heterocyclic group Chemical group 0.000 claims description 104
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 98
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 claims description 98
- 229910052801 chlorine Inorganic materials 0.000 claims description 95
- 229910052740 iodine Inorganic materials 0.000 claims description 93
- 125000000304 alkynyl group Chemical group 0.000 claims description 87
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 86
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 79
- 229910052794 bromium Inorganic materials 0.000 claims description 77
- 229910052799 carbon Inorganic materials 0.000 claims description 72
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 72
- JCXJVPUVTGWSNB-UHFFFAOYSA-N nitrogen dioxide Inorganic materials O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 64
- 125000004432 carbon atom Chemical group C* 0.000 claims description 57
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 56
- OTXBWGUYZNKPMG-UHFFFAOYSA-N isofulminic acid Chemical compound O[N+]#[C-] OTXBWGUYZNKPMG-UHFFFAOYSA-N 0.000 claims description 54
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 50
- 239000001257 hydrogen Substances 0.000 claims description 50
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 48
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 48
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 46
- 101100294115 Caenorhabditis elegans nhr-4 gene Proteins 0.000 claims description 43
- 101100516568 Caenorhabditis elegans nhr-7 gene Proteins 0.000 claims description 43
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims description 41
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims description 40
- 125000000565 sulfonamide group Chemical group 0.000 claims description 39
- 101100240518 Caenorhabditis elegans nhr-12 gene Proteins 0.000 claims description 37
- 125000003545 alkoxy group Chemical group 0.000 claims description 37
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 37
- IQHXABCGSFAKPN-UHFFFAOYSA-N pyrrolidine-3-carboxamide Chemical compound NC(=O)C1CCNC1 IQHXABCGSFAKPN-UHFFFAOYSA-N 0.000 claims description 37
- 101100240517 Caenorhabditis elegans nhr-11 gene Proteins 0.000 claims description 36
- 108091008648 NR7C Proteins 0.000 claims description 35
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- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 33
- 101100294106 Caenorhabditis elegans nhr-3 gene Proteins 0.000 claims description 31
- 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 claims description 30
- 150000002431 hydrogen Chemical class 0.000 claims description 26
- 101100516563 Caenorhabditis elegans nhr-6 gene Proteins 0.000 claims description 25
- 108020004021 3-ketosteroid receptors Proteins 0.000 claims description 23
- 241001139947 Mida Species 0.000 claims description 23
- 229910006074 SO2NH2 Inorganic materials 0.000 claims description 23
- 101100516554 Caenorhabditis elegans nhr-5 gene Proteins 0.000 claims description 21
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 21
- 125000006334 2,4-difluoro benzoyl group Chemical group [H]C1=C([H])C(C(*)=O)=C(F)C([H])=C1F 0.000 claims description 20
- 125000001188 haloalkyl group Chemical group 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 18
- 125000001072 heteroaryl group Chemical group 0.000 claims description 18
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 17
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- 125000006639 cyclohexyl carbonyl group Chemical group 0.000 claims description 12
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- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 12
- 125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 claims description 11
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- 125000003541 2-chlorobenzoyl group Chemical group ClC1=C(C(=O)*)C=CC=C1 0.000 claims description 10
- 125000004122 cyclic group Chemical group 0.000 claims description 10
- DENPQNAWGQXKCU-UHFFFAOYSA-N thiophene-2-carboxamide Chemical compound NC(=O)C1=CC=CS1 DENPQNAWGQXKCU-UHFFFAOYSA-N 0.000 claims description 10
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 9
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 9
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 9
- KGEXKCMGYQQMLW-UHFFFAOYSA-N n-pyridazin-3-ylazetidine-3-carboxamide Chemical compound C1NCC1C(=O)NC1=CC=CN=N1 KGEXKCMGYQQMLW-UHFFFAOYSA-N 0.000 claims description 9
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 8
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- 101100212791 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) YBL068W-A gene Proteins 0.000 claims description 8
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- CRSOQBOWXPBRES-UHFFFAOYSA-N neopentane Chemical compound CC(C)(C)C CRSOQBOWXPBRES-UHFFFAOYSA-N 0.000 claims description 8
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 7
- 241000927721 Tritia Species 0.000 claims description 7
- 125000006638 cyclopentyl carbonyl group Chemical group 0.000 claims description 7
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 7
- XAGZJIQIVXSURR-UHFFFAOYSA-N 1-[4-(trifluoromethyl)phenyl]piperidin-2-one Chemical group C1=CC(C(F)(F)F)=CC=C1N1C(=O)CCCC1 XAGZJIQIVXSURR-UHFFFAOYSA-N 0.000 claims description 6
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 6
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- JOLLWYKRXONOQC-UHFFFAOYSA-N n-pyridazin-3-ylpyrrolidine-3-carboxamide Chemical compound C1CNCC1C(=O)NC1=CC=CN=N1 JOLLWYKRXONOQC-UHFFFAOYSA-N 0.000 claims description 5
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- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 4
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-
2013
- 2013-05-10 US US13/891,357 patent/US8975398B2/en active Active
- 2013-05-10 CN CN201380036867.6A patent/CN104583194A/zh active Pending
- 2013-05-10 CA CA2873097A patent/CA2873097A1/en not_active Abandoned
- 2013-05-10 HK HK15110586.2A patent/HK1209739A1/xx unknown
- 2013-05-10 MX MX2014013751A patent/MX2014013751A/es unknown
- 2013-05-10 WO PCT/US2013/040481 patent/WO2013170115A1/en not_active Ceased
- 2013-05-10 JP JP2015511730A patent/JP2015520752A/ja active Pending
- 2013-05-10 AR ARP130101637A patent/AR091023A1/es unknown
- 2013-05-10 EP EP13726339.8A patent/EP2847181A1/en not_active Withdrawn
- 2013-05-10 TW TW102116746A patent/TW201350478A/zh unknown
- 2013-05-10 US US13/891,354 patent/US20130303509A1/en not_active Abandoned
- 2013-05-10 UY UY0001034804A patent/UY34804A/es not_active Application Discontinuation
-
2015
- 2015-01-23 US US14/603,832 patent/US20150141398A1/en not_active Abandoned
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2016
- 2016-11-21 US US15/357,383 patent/US20170065575A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US8975398B2 (en) | 2015-03-10 |
| WO2013170115A1 (en) | 2013-11-14 |
| US20150141398A1 (en) | 2015-05-21 |
| HK1209739A1 (en) | 2016-04-08 |
| JP2015520752A (ja) | 2015-07-23 |
| US20170065575A1 (en) | 2017-03-09 |
| CA2873097A1 (en) | 2013-11-14 |
| AR091023A1 (es) | 2014-12-30 |
| CN104583194A (zh) | 2015-04-29 |
| US20130303510A1 (en) | 2013-11-14 |
| EP2847181A1 (en) | 2015-03-18 |
| US20130303509A1 (en) | 2013-11-14 |
| UY34804A (es) | 2013-12-31 |
| TW201350478A (zh) | 2013-12-16 |
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