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 (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8975398B2 (en) * | 2012-05-11 | 2015-03-10 | Abbvie Inc. | NAMPT inhibitors |
| TWI731535B (zh) | 2014-03-21 | 2021-06-21 | 美商艾伯維有限公司 | 抗-egfr抗體及抗體藥物結合物 |
| KR102359214B1 (ko) | 2014-04-04 | 2022-02-07 | 델 마 파마슈티컬스 | 폐의 비소세포 암종 및 난소암을 치료하기 위한 디안하이드로갈락티톨 및 이의 유사체 또는 유도체 |
| US10144742B2 (en) | 2014-04-18 | 2018-12-04 | Millennium Pharmaceuticals, Inc. | Quinoxaline compounds and uses thereof |
| CN110526912B (zh) | 2014-06-19 | 2023-02-14 | 武田药品工业株式会社 | 用于激酶抑制的杂芳基化合物 |
| EP3247705B1 (en) | 2015-01-20 | 2019-11-20 | Millennium Pharmaceuticals, Inc. | Quinazoline and quinoline compounds and uses thereof as nampt inhibitors |
| EP4067368A1 (en) | 2016-06-01 | 2022-10-05 | Athira Pharma, Inc. | Compounds |
| EP3469000A1 (en) | 2016-06-08 | 2019-04-17 | AbbVie Inc. | Anti-b7-h3 antibodies and antibody drug conjugates |
| JP2019521975A (ja) | 2016-06-08 | 2019-08-08 | アッヴィ・インコーポレイテッド | 抗ｅｇｆｒ抗体薬物コンジュゲート |
| EP3458479B1 (en) | 2016-06-08 | 2020-11-04 | AbbVie Inc. | Anti-b7-h3 antibodies and antibody drug conjugates |
| BR112018075630A2 (pt) | 2016-06-08 | 2019-03-19 | Abbvie Inc. | anticorpos anti-cd98 e conjugados de fármaco de anticorpo |
| BR112018075639A2 (pt) | 2016-06-08 | 2019-04-09 | Abbvie Inc. | conjugados de anticorpo fármaco anti-egfr |
| JP2019526529A (ja) | 2016-06-08 | 2019-09-19 | アッヴィ・インコーポレイテッド | 抗ｂ７−ｈ３抗体及び抗体薬物コンジュゲート |
| AU2017281907B2 (en) | 2016-06-23 | 2021-10-21 | St. Jude Children's Research Hospital, Inc. | Small molecule modulators of pantothenate kinases |
| TWI835714B (zh) | 2016-10-18 | 2024-03-21 | 美商思進公司 | 菸鹼醯胺腺嘌呤二核苷酸補救合成(salvage pathway)抑制劑之靶向投遞 |
| EP3554544A4 (en) | 2016-12-16 | 2020-07-29 | Bluefin Biomedicine, Inc. | ANTI-PROTEIN 1 ANTIBODY CONTAINING AN ANTI-CUB DOMAIN (CDCP1), ANTIBODY-DRUG CONJUGATES AND THEIR METHODS OF USE |
| WO2018124001A1 (ja) | 2016-12-27 | 2018-07-05 | 国立研究開発法人理化学研究所 | Ｂｍｐシグナル阻害化合物 |
| WO2018177993A1 (de) | 2017-03-31 | 2018-10-04 | Bayer Cropscience Aktiengesellschaft | Pyrazole zur bekämpfung von arthropoden |
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| WO2018201087A1 (en) | 2017-04-27 | 2018-11-01 | Seattle Genetics, Inc. | Quaternized nicotinamide adenine dinucleotide salvage pathway inhibitor conjugates |
| CA3066918A1 (en) | 2017-06-12 | 2018-12-20 | Bluefin Biomedicine, Inc. | Anti-il1rap antibodies and antibody drug conjugates |
| EP3731859B1 (en) | 2017-12-27 | 2025-08-20 | St. Jude Children's Research Hospital, Inc. | Pyridazine compounds for use to treat disorders associated with castor |
| KR102728619B1 (ko) | 2017-12-27 | 2024-11-08 | 세인트 쥬드 칠드런즈 리써치 호스피탈, 인코포레이티드 | 판토테네이트 키나제의 소분자 조절제 |
| JP2021512103A (ja) * | 2018-01-31 | 2021-05-13 | バイエル アクチェンゲゼルシャフトＢａｙｅｒ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | Ｎａｍｐｔ阻害剤を含む抗体薬物複合体（ａｄｃｓ） |
| TWI707849B (zh) | 2018-02-13 | 2020-10-21 | 美商基利科學股份有限公司 | Pd‐1/pd‐l1抑制劑 |
| KR102591947B1 (ko) | 2018-04-19 | 2023-10-25 | 길리애드 사이언시즈, 인코포레이티드 | Pd-1/pd-l1 억제제 |
| US12084431B2 (en) | 2018-05-14 | 2024-09-10 | Takeda Pharmaceutical Company Limited | Pharmaceutical salts of pyrimidine derivatives and method of treating disorders |
| EP3820572B1 (en) | 2018-07-13 | 2023-08-16 | Gilead Sciences, Inc. | Pd-1/pd-l1 inhibitors |
| US20210388018A1 (en) * | 2018-10-01 | 2021-12-16 | Cornell University | Methyl and ethyl nicotinate-riboside-5-phosphates, preparation thereof and methods of use thereof |
| US11236085B2 (en) | 2018-10-24 | 2022-02-01 | Gilead Sciences, Inc. | PD-1/PD-L1 inhibitors |
| 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 |
| CA3135011A1 (en) | 2019-03-27 | 2020-10-01 | St. Jude Children's Research Hospital | Small molecule modulators of pank |
| US20220267271A1 (en) * | 2019-07-08 | 2022-08-25 | Mayo Foundation For Medical Education And Research | Wnt activators and methods of use |
| US11807626B2 (en) | 2020-04-23 | 2023-11-07 | Opna Bio SA | Compounds and methods for CD73 modulation and indications therefor |
| IL298760A (en) | 2020-06-05 | 2023-02-01 | Kinnate Biopharma Inc | Fibroblast growth factor receptor kinase inhibitors |
| 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 |
| UY39610A (es) | 2021-01-20 | 2022-08-31 | Abbvie Inc | Conjugados anticuerpo-fármaco anti-egfr |
| KR20250134734A (ko) | 2022-12-16 | 2025-09-11 | 페온 테라퓨틱스 리미티드 | Cub 도메인-함유 단백질 1(cdcp1)에 대한 항체 및 이의 용도 |
| 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 |
|---|---|---|---|---|
| EP0690847A1 (en) | 1993-03-29 | 1996-01-10 | Zeneca Limited | Heterocyclic compounds as platelet aggregation inhibitors |
| 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 |
| PT1019385E (pt) | 1995-09-15 | 2004-06-30 | Upjohn Co | N-oxidos de aminoaril-oxazolidinona |
| 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 |
| US6372759B1 (en) | 1997-06-26 | 2002-04-16 | 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 |
| WO2002006234A1 (en) | 2000-07-17 | 2002-01-24 | Takeda Chemical Industries, Ltd. | Sulfone derivatives, process for their production and use thereof |
| ATE427935T1 (de) | 2001-08-07 | 2009-04-15 | Banyu Pharma Co Ltd | Spiro isobenzofurane als neuropeptid y rezeptor antagonisten |
| HUP0200849A2 (hu) * | 2002-03-06 | 2004-08-30 | Sanofi-Synthelabo | N-aminoacetil-2-ciano-pirrolidin-származékok, e vegyületeket tartalmazó gyógyszerkészítmények és eljárás előállításukra |
| MXPA04008796A (es) | 2002-03-13 | 2004-11-26 | Janssen Pharmaceutica Nv | Derivados de carbonilamino como novedosos inhibidores de desacetilasa de histona. |
| 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 |
| KR101153335B1 (ko) | 2003-09-24 | 2012-07-05 | 메틸진 인코포레이티드 | 히스톤 데아세틸라제의 억제제 |
| CA2547080A1 (en) | 2003-12-02 | 2005-07-28 | Vertex Pharmaceuticals, Inc. | Heterocyclic protein kinase inhibitors and uses thereof |
| CA2551611C (en) * | 2003-12-26 | 2013-06-25 | Kyowa Kirin Co., Ltd. | Thiazole derivatives for treating or preventing parkinson's disease |
| WO2005099353A2 (en) | 2004-04-19 | 2005-10-27 | Symed Labs Limited | A novel process for the preparation of linezolid and related compounds |
| EP1768967B1 (en) | 2004-07-20 | 2009-04-22 | Symed Labs Limited | Novel intermediates for linezolid and related compounds |
| WO2006039164A2 (en) | 2004-09-29 | 2006-04-13 | Amr Technology, Inc. | Novel cyclosporin analogues and their pharmaceutical uses |
| 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 |
| CN101171250A (zh) | 2005-03-04 | 2008-04-30 | 阿斯利康(瑞典)有限公司 | 具有抗菌活性的氮杂环丁烷和吡咯的三环衍生物 |
| 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 |
| KR101507375B1 (ko) | 2006-09-15 | 2015-04-07 | 엑스커버리 홀딩 컴퍼니 엘엘씨 | 키나아제 억제제 화합물 |
| US8796267B2 (en) | 2006-10-23 | 2014-08-05 | Concert Pharmaceuticals, Inc. | Oxazolidinone derivatives and methods of use |
| EP2129660A2 (en) * | 2006-12-19 | 2009-12-09 | Pfizer Products Inc. | Nicotinamide derivatives as inhibitors of h-pgds and their use for treating prostaglandin d2 mediated diseases |
| CA2676944C (en) | 2007-02-15 | 2016-01-19 | F. Hoffmann-La Roche Ag | 2-aminooxazolines as taar1 ligands |
| JP2010524972A (ja) | 2007-04-19 | 2010-07-22 | コンサート ファーマシューティカルズ インコーポレイテッド | 重水素化したモルホリニル化合物 |
| 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 |
| EP2209774A1 (en) | 2007-10-02 | 2010-07-28 | Concert Pharmaceuticals Inc. | Pyrimidinedione derivatives |
| WO2009051782A1 (en) | 2007-10-18 | 2009-04-23 | Concert Pharmaceuticals Inc. | Deuterated etravirine |
| US20090105338A1 (en) | 2007-10-18 | 2009-04-23 | Protia, Llc | Deuterium-enriched gabexate mesylate |
| AU2008317375B2 (en) | 2007-10-26 | 2013-02-28 | 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 |
| MY150379A (en) | 2008-02-26 | 2013-12-31 | Takeda Pharmaceutical | Fused heterocyclic derivative and use 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 |
| CA2748099C (en) | 2008-12-22 | 2017-02-28 | Array Biopharma Inc. | 7-phenoxychroman carboxylic acid derivatives |
| WO2011025799A1 (en) | 2009-08-26 | 2011-03-03 | Glaxo Group Limited | Cathepsin c inhibitors |
| CN106243023A (zh) | 2010-09-03 | 2016-12-21 | 福马Tm有限责任公司 | 用于抑制nampt的胍化合物和组合物 |
| EP2832731A4 (en) * | 2012-03-27 | 2015-08-19 | Shionogi & Co | AROMATIC HETEROCYCLIC CHAIN 5-CORE DERIVED DERIVATIVE HAVING TRPV4 INHIBITORY 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 |
-
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 JP JP2015511730A patent/JP2015520752A/ja active Pending
- 2013-05-10 TW TW102116746A patent/TW201350478A/zh unknown
- 2013-05-10 EP EP13726339.8A patent/EP2847181A1/en not_active Withdrawn
- 2013-05-10 WO PCT/US2013/040481 patent/WO2013170115A1/en not_active Ceased
- 2013-05-10 HK HK15110586.2A patent/HK1209739A1/xx unknown
- 2013-05-10 US US13/891,354 patent/US20130303509A1/en not_active Abandoned
- 2013-05-10 CA CA2873097A patent/CA2873097A1/en not_active Abandoned
- 2013-05-10 MX MX2014013751A patent/MX2014013751A/es unknown
- 2013-05-10 UY UY0001034804A patent/UY34804A/es not_active Application Discontinuation
- 2013-05-10 AR ARP130101637A patent/AR091023A1/es unknown
-
2015
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2016
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Also Published As
| Publication number | Publication date |
|---|---|
| WO2013170115A1 (en) | 2013-11-14 |
| CN104583194A (zh) | 2015-04-29 |
| CA2873097A1 (en) | 2013-11-14 |
| UY34804A (es) | 2013-12-31 |
| JP2015520752A (ja) | 2015-07-23 |
| US20170065575A1 (en) | 2017-03-09 |
| HK1209739A1 (en) | 2016-04-08 |
| US20150141398A1 (en) | 2015-05-21 |
| US8975398B2 (en) | 2015-03-10 |
| US20130303510A1 (en) | 2013-11-14 |
| AR091023A1 (es) | 2014-12-30 |
| US20130303509A1 (en) | 2013-11-14 |
| TW201350478A (zh) | 2013-12-16 |
| EP2847181A1 (en) | 2015-03-18 |
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