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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Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
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| TW202330606A (zh) | 2014-03-21 | 2023-08-01 | 美商艾伯維有限公司 | 抗-egfr抗體及抗體藥物結合物 |
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| US10323018B2 (en) | 2015-01-20 | 2019-06-18 | Millennium Pharmaceuticals, Inc. | Quinazoline and quinoline compounds and uses thereof |
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| JP2019524651A (ja) | 2016-06-08 | 2019-09-05 | アッヴィ・インコーポレイテッド | 抗ｃｄ９８抗体及び抗体薬物コンジュゲート |
| BR112018075639A2 (pt) | 2016-06-08 | 2019-04-09 | Abbvie Inc. | conjugados de anticorpo fármaco anti-egfr |
| CN109561680B (zh) | 2016-06-23 | 2021-07-13 | 圣朱德儿童研究医院 | 泛酸激酶的小分子调节剂 |
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| TW201904613A (zh) | 2017-04-27 | 2019-02-01 | 美商西雅圖遺傳學公司 | 季鹼化菸鹼醯胺腺二核苷酸補救合成抑制劑結合物 |
| CN118994394A (zh) | 2017-06-12 | 2024-11-22 | 蓝鳍生物医药公司 | 抗-il1rap抗体和抗体药物缀合物 |
| BR112020012875A2 (pt) | 2017-12-27 | 2021-01-05 | St. Jude Children¿S Research Hospital, Inc. | Moduladores de pequenas moléculas das pantotenato quinases |
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| CA3089754A1 (en) * | 2018-01-31 | 2019-08-08 | Bayer Aktiengesellschaft | Antibody drug conjugates (adcs) with nampt inhibitors |
| KR102708681B1 (ko) | 2018-02-13 | 2024-09-26 | 길리애드 사이언시즈, 인코포레이티드 | Pd-1/pd-l1 억제제 |
| EP3781556B1 (en) | 2018-04-19 | 2025-06-18 | Gilead Sciences, Inc. | Pd-1/pd-l1 inhibitors |
| AU2019269372A1 (en) | 2018-05-14 | 2020-11-26 | Takeda Pharmaceutical Company Limited | Pharmaceutical salts of pyrimidine derivatives and method of treating disorders |
| CN118221646A (zh) | 2018-07-13 | 2024-06-21 | 吉利德科学公司 | Pd-1/pd-l1抑制剂 |
| US20210388018A1 (en) * | 2018-10-01 | 2021-12-16 | Cornell University | Methyl and ethyl nicotinate-riboside-5-phosphates, preparation thereof and methods of use thereof |
| KR102635333B1 (ko) | 2018-10-24 | 2024-02-15 | 길리애드 사이언시즈, 인코포레이티드 | Pd-1/pd-l1 억제제 |
| WO2020179859A1 (ja) | 2019-03-06 | 2020-09-10 | 第一三共株式会社 | ピロロピラゾール誘導体 |
| WO2021007313A1 (en) * | 2019-07-08 | 2021-01-14 | Mayo Foundation For Medical Education And Research | Wnt activators and methods of use |
| AU2021261383A1 (en) | 2020-04-23 | 2022-11-17 | Opna Bio SA | Compounds and methods for CD73 modulation and indications therefor |
| JP2023529867A (ja) | 2020-06-05 | 2023-07-12 | キネート バイオファーマ インク． | 線維芽細胞増殖因子受容体キナーゼの阻害剤 |
| CN114660219A (zh) * | 2020-12-23 | 2022-06-24 | 安徽古特生物科技有限公司 | 一种β-烟酰胺单核苷酸的检测方法 |
| AR124681A1 (es) | 2021-01-20 | 2023-04-26 | Abbvie Inc | Conjugados anticuerpo-fármaco anti-egfr |
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| CN117285573B (zh) * | 2023-09-26 | 2024-03-26 | 长沙兴嘉生物工程股份有限公司 | 一种β-烟酰胺单核苷酸金属络合物及其制备方法 |
Family Cites Families (57)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ262942A (en) | 1993-03-29 | 1997-07-27 | Zeneca Ltd | Pyridyl substituted piperazine and various other derivatives of azaheteroaryl substituted piperazines; pharmaceutical compositions |
| MY115155A (en) | 1993-09-09 | 2003-04-30 | Upjohn Co | Substituted oxazine and thiazine oxazolidinone antimicrobials. |
| IL115420A0 (en) | 1994-09-26 | 1995-12-31 | Zeneca Ltd | Aminoheterocyclic derivatives |
| ES2214546T3 (es) | 1995-09-15 | 2004-09-16 | PHARMACIA & UPJOHN COMPANY | N-oxidos de aminoariloxazolidinona. |
| DE19624659A1 (de) | 1996-06-20 | 1998-01-08 | Klinge Co Chem Pharm Fab | Neue Pyridylalken- und Pyridylalkinsäureamide |
| DE19624668A1 (de) | 1996-06-20 | 1998-02-19 | Klinge Co Chem Pharm Fab | Verwendung von Pyridylalkan-, Pyridylalken- bzw. Pyridylalkinsäureamiden |
| AU8270298A (en) | 1997-06-26 | 1999-01-19 | Eli Lilly And Company | Antithrombotic agents |
| EP1014962A4 (en) | 1997-06-26 | 2007-06-27 | Lilly Co Eli | ANTITHROMBOTIC AGENTS |
| US20030220234A1 (en) | 1998-11-02 | 2003-11-27 | Selvaraj Naicker | Deuterated cyclosporine analogs and their use as immunodulating agents |
| GB9918037D0 (en) | 1999-07-30 | 1999-09-29 | Biochemie Gmbh | Organic compounds |
| GB0010757D0 (en) | 2000-05-05 | 2000-06-28 | Astrazeneca Ab | Chemical compounds |
| AU2001269531A1 (en) | 2000-07-17 | 2002-01-30 | Takeda Chemical Industries Ltd. | Sulfone derivatives, process for their production and use thereof |
| WO2003014083A1 (en) | 2001-08-07 | 2003-02-20 | Banyu Pharmaceutical Co., Ltd. | Spiro compounds |
| HUP0200849A2 (hu) * | 2002-03-06 | 2004-08-30 | Sanofi-Synthelabo | N-aminoacetil-2-ciano-pirrolidin-származékok, e vegyületeket tartalmazó gyógyszerkészítmények és eljárás előállításukra |
| ES2306858T3 (es) | 2002-03-13 | 2008-11-16 | Janssen Pharmaceutica Nv | Derivados de carbonilamino como nuevos inhibidores de las histonadesacetilasas. |
| EP1348434A1 (en) | 2002-03-27 | 2003-10-01 | Fujisawa Deutschland GmbH | Use of pyridyl amides as inhibitors of angiogenesis |
| GB0319150D0 (en) * | 2003-08-14 | 2003-09-17 | Glaxo Group Ltd | Novel compounds |
| EP1663953A1 (en) | 2003-09-24 | 2006-06-07 | Methylgene, Inc. | Inhibitors of histone deacetylase |
| US7244735B2 (en) | 2003-12-02 | 2007-07-17 | Vertex Pharmaceuticals Inc. | Heterocyclic protein kinase inhibitors and uses thereof |
| ES2629414T3 (es) * | 2003-12-26 | 2017-08-09 | Kyowa Hakko Kirin Co., Ltd. | Derivados de tiazol |
| DE602004009344T2 (de) | 2004-04-19 | 2008-07-10 | Symed Labs Ltd., Hyderabad | Neues verfahren zur herstellung von linezolid und verwandten verbindungen |
| PL1768967T3 (pl) | 2004-07-20 | 2009-09-30 | Symed Labs Ltd | Nowe związki pośrednie do wytwarzania linezolidu oraz związki pokrewne |
| JP2008514702A (ja) | 2004-09-29 | 2008-05-08 | エーエムアール テクノロジー インコーポレイテッド | 新規シクロスポリン類似体およびそれらの薬学的使用 |
| WO2006058338A2 (en) | 2004-11-29 | 2006-06-01 | Janssen Pharmaceutica N.V. | 4 - piperidinecarboxamide derivatives as modulators of vanilloid vr1 receptor |
| UA90706C2 (ru) * | 2005-02-24 | 2010-05-25 | Милленниум Фармасьютикалз, Инк. | Антагонисты рецептора pgd2 для лечения воспалительных заболеваний |
| US20090253671A1 (en) | 2005-03-04 | 2009-10-08 | Astrazeneca Ab | Tricyclic derivatives of azetidine and pyrrole with antibacterial activity |
| TW200716636A (en) | 2005-05-31 | 2007-05-01 | Speedel Experimenta Ag | Heterocyclic spiro-compounds |
| US7514068B2 (en) | 2005-09-14 | 2009-04-07 | Concert Pharmaceuticals Inc. | Biphenyl-pyrazolecarboxamide compounds |
| WO2007076055A2 (en) * | 2005-12-22 | 2007-07-05 | Entremed, Inc. | Compositions and methods comprising proteinase activated receptor antagonists |
| TW200800997A (en) | 2006-03-22 | 2008-01-01 | Astrazeneca Ab | Chemical compounds |
| TW200815426A (en) | 2006-06-28 | 2008-04-01 | Astrazeneca Ab | New pyridine analogues II 333 |
| WO2008026018A1 (en) | 2006-09-01 | 2008-03-06 | Topotarget Switzerland Sa | New method for the treatment of inflammatory diseases |
| JP5568304B2 (ja) * | 2006-09-15 | 2014-08-06 | タイロジェネクス，インコーポレイテッド | キナーゼ阻害剤化合物 |
| US8796267B2 (en) | 2006-10-23 | 2014-08-05 | Concert Pharmaceuticals, Inc. | Oxazolidinone derivatives and methods of use |
| JP2010513458A (ja) * | 2006-12-19 | 2010-04-30 | ファイザー・プロダクツ・インク | Ｈ−ｐｇｄｓの阻害剤としてのニコチンアミド誘導体、およびプロスタグランジンｄ２の仲介による疾患を治療するためのその使用 |
| CA2676944C (en) | 2007-02-15 | 2016-01-19 | F. Hoffmann-La Roche Ag | 2-aminooxazolines as taar1 ligands |
| AU2008242703B2 (en) | 2007-04-19 | 2011-08-18 | Concert Pharmaceuticals Inc. | Deuterated morpholinyl compounds |
| US7531685B2 (en) | 2007-06-01 | 2009-05-12 | Protia, Llc | Deuterium-enriched oxybutynin |
| US20090131485A1 (en) | 2007-09-10 | 2009-05-21 | Concert Pharmaceuticals, Inc. | Deuterated pirfenidone |
| US20090118238A1 (en) | 2007-09-17 | 2009-05-07 | Protia, Llc | Deuterium-enriched alendronate |
| US20090088416A1 (en) | 2007-09-26 | 2009-04-02 | Protia, Llc | Deuterium-enriched lapaquistat |
| US20090082471A1 (en) | 2007-09-26 | 2009-03-26 | Protia, Llc | Deuterium-enriched fingolimod |
| US20090137457A1 (en) | 2007-10-02 | 2009-05-28 | Concert Pharmaceuticals, Inc. | Pyrimidinedione derivatives |
| US20090105338A1 (en) | 2007-10-18 | 2009-04-23 | Protia, Llc | Deuterium-enriched gabexate mesylate |
| EP2212298B1 (en) | 2007-10-18 | 2013-03-27 | Concert Pharmaceuticals Inc. | Deuterated etravirine |
| CA2703591C (en) | 2007-10-26 | 2013-05-07 | Concert Pharmaceuticals, Inc. | Deuterated darunavir |
| US20090113874A1 (en) | 2007-11-02 | 2009-05-07 | Caterpillar Inc. | System and method for electrically regenerating a particulate filter assembly of a generator set |
| GEP20125664B (en) | 2008-02-26 | 2012-10-10 | Takeda Pharmaceuticals Co | Condensed heterocyclic derivatives and application thereof |
| EP2098231A1 (en) | 2008-03-05 | 2009-09-09 | Topotarget Switzerland SA | Use of NAD formation inhibitors for the treatment of ischemia-reperfusion injury |
| JP2011527667A (ja) | 2008-06-18 | 2011-11-04 | 武田薬品工業株式会社 | ハロ置換ピリミドジアゼピン |
| WO2010075200A1 (en) | 2008-12-22 | 2010-07-01 | Array Biopharma Inc. | 7-phenoxychroman carboxylic acid derivatives |
| WO2011025799A1 (en) | 2009-08-26 | 2011-03-03 | Glaxo Group Limited | Cathepsin c inhibitors |
| JP5881705B2 (ja) * | 2010-09-03 | 2016-03-09 | フォーマ ティーエム， エルエルシー． | Ｎａｍｐｔの阻害のための新規化合物及び組成物 |
| US9499533B2 (en) * | 2012-03-27 | 2016-11-22 | Shionogi & Co., Ltd. | Aromatic 5-membered heterocyclic derivative having TRPV4-Inhibiting activity |
| AU2013241854B2 (en) * | 2012-03-28 | 2017-11-02 | Intervet International B.V. | Heteroaryl compounds with cyclic bridging unit for use in the treatment helminth infection |
| US8975398B2 (en) * | 2012-05-11 | 2015-03-10 | Abbvie Inc. | NAMPT inhibitors |
| US9296723B2 (en) * | 2012-05-11 | 2016-03-29 | Abbvie Inc. | NAMPT inhibitors |
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2013
- 2013-05-10 US US13/891,357 patent/US8975398B2/en active Active
- 2013-05-10 MX MX2014013751A patent/MX2014013751A/es unknown
- 2013-05-10 UY UY0001034804A patent/UY34804A/es not_active Application Discontinuation
- 2013-05-10 JP JP2015511730A patent/JP2015520752A/ja active Pending
- 2013-05-10 TW TW102116746A patent/TW201350478A/zh unknown
- 2013-05-10 HK HK15110586.2A patent/HK1209739A1/xx unknown
- 2013-05-10 AR ARP130101637A patent/AR091023A1/es unknown
- 2013-05-10 CA CA2873097A patent/CA2873097A1/en not_active Abandoned
- 2013-05-10 EP EP13726339.8A patent/EP2847181A1/en not_active Withdrawn
- 2013-05-10 CN CN201380036867.6A patent/CN104583194A/zh active Pending
- 2013-05-10 WO PCT/US2013/040481 patent/WO2013170115A1/en not_active Ceased
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2015
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2016
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Also Published As
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|---|---|
| AR091023A1 (es) | 2014-12-30 |
| US20150141398A1 (en) | 2015-05-21 |
| US20130303509A1 (en) | 2013-11-14 |
| EP2847181A1 (en) | 2015-03-18 |
| JP2015520752A (ja) | 2015-07-23 |
| CA2873097A1 (en) | 2013-11-14 |
| US8975398B2 (en) | 2015-03-10 |
| US20130303510A1 (en) | 2013-11-14 |
| TW201350478A (zh) | 2013-12-16 |
| CN104583194A (zh) | 2015-04-29 |
| WO2013170115A1 (en) | 2013-11-14 |
| US20170065575A1 (en) | 2017-03-09 |
| HK1209739A1 (en) | 2016-04-08 |
| UY34804A (es) | 2013-12-31 |
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