Optimization of Allosteric With-No-Lysine (WNK) Kinase Inhibitors and Efficacy in Rodent Hypertension Models

Journal of Medicinal Chemistry

Volumn 60, Issue 16, 2017, Pages 7099-7107

  Yamada, Ken ^a,b   Levell, Julian ^a,c   Yoon, Taeyong ^a,d   Kohls, Darcy ^a   Yowe, David ^a   Rigel, Dean F ^a,e   Imase, Hidetomo ^a   Yuan, Jun ^a   Yasoshima, Kayo ^a,b   Dipetrillo, Keith ^a,f   Monovich, Lauren ^a   Xu, Lingfei ^a   Zhu, Meicheng ^a,g   Kato, Mitsunori ^a,b   Jain, Monish ^a   Idamakanti, Neeraja ^a,h   Taslimi, Paul ^a,i   Kawanami, Toshio ^a,b   Argikar, Upendra A ^a   Kunjathoor, Vidya ^a   Xie, Xiaoling ^a   Yagi, Yukiko I ^b,j   Iwaki, Yuki ^a,k   Robinson, Zachary ^a,l   Park, Hyi Man ^a,b   more..

^a NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

^b NOVARTIS PHARMA K K   (Japan)

^c Department of Structural Biology   (United States)

^d Dong A ST Co Ltd   (South Korea)

^e Rigel BioPharma Consulting LLC   (United States)

^f Insmed   (United States)

^g Transamerica   (United States)

^h TAKEDA PHARMACEUTICALS   (United States)

ⁱ MERCK RESEARCH LABORATORIES   (United States)

^j FUJIFILM CORPORATION   (Japan)

^k Janssen Pharmaceutical KK   (Japan)

^l Short Path Distillery Inc   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

(4 BENZYLPIPERAZIN 1 YL)[2 (3 METHOXYPHENYL)QUINOLIN 4 YL]METHANONE; 1 ([1,1' BIPHENYL] 3 YL) 1H INDOLE 3 CARBOXALDEHYDE; 1 CYCLOHEXYL N [[1 (3' METHOXYBIPHENYL 3 YL) 1H INDOL 3 YL]METHYL]METHANAMINE; 1 CYCLOHEXYL N [[1 [2 (3 METHOXYPHENYL)PYRIDIN 4 YL] 1H INDOL 3 YL]METHYL]METHANAMINE; 1 CYCLOHEXYL N [[6 FLUORO 1 [2 (3 METHOXYPHENYL)PYRIDIN 4 YL] 1H INDOL 3 YL]METHYL]METHANAMINE; 1 [1 [([1,1' BIPHENYL] 3 YL) 1H INDOL 3 YL] N (CYCLOHEXYLMETHYL)METHANAMINE; 2 [2 (METHYLAMINO)THIAZOL 4 YL]ISONICOTINIC ACID; ADENOSINE TRIPHOSPHATE; ANTIHYPERTENSIVE AGENT; METHYL 2 [2 (METHYLAMINO)THIAZOL 4 YL]ISONICOTINATE; N [1 (4 CHLOROBENZYL)PYRROLIDIN 3 YL] 2 (3 METHOXYPHENYL) N METHYLQUINOLINE 4 CARBOXAMIDE; N [[1 [2 (3 METHOXYPHENYL) 5 METHYLPYRIDIN 4 YL] 1H INDOL 3 YL]METHYL] 2 METHYLPROPAN 1 AMINE; PHOSPHOTRANSFERASE INHIBITOR; PROTEIN KINASE WNK1; PROTEIN KINASE WNK2; PROTEIN KINASE WNK4; UNCLASSIFIED DRUG; WITH NO LYSINE KINASE INHIBITOR; [2 (3 METHOXYPHENYL)QUINOLIN 4 YL](PIPERAZIN 1 YL)METHANONE; [4 (4 CHLOROBENZYL)PIPERAZIN 1 YL)[2 (3 METHOXYPHENYL)PYRIDIN 4 YL]METHANONE; [4 (4 CHLOROBENZYL)PIPERAZIN 1 YL][2 [2 (METHYLAMINO)THIAZOL 4 YL]PYRIDIN 4 YL]METHANONE; [5 CHLORO 2 [2 (METHYLAMINO)THIAZOL 4 YL]PYRIDIN 4 YL][4 (4 CHLOROBENZYL)PIPERAZIN 1 YL]METHANONE; [5 CHLORO 2 [2 [(METHYL D3)AMINO]THIAZOL 4 YL]PYRIDIN 4 YL][4 (4 CHLOROBENZYL)PIPERAZIN 1 YL]METHANONE; (5-CHLORO-2-(2-((METHYL)AMINO)THIAZOL-4-YL)PYRIDIN-4-YL)(4-(4-CHLOROBENZYL)PIPERAZIN-1-YL)METHANONE; MINOR HISTOCOMPATIBILITY ANTIGEN; OSR1 KINASE, HUMAN; PIPERAZINE DERIVATIVE; PROTEIN KINASE INHIBITOR; PROTEIN SERINE THREONINE KINASE; SIGNAL PEPTIDE; THIAZOLE DERIVATIVE; WNK1 PROTEIN, HUMAN; WNK2 PROTEIN, HUMAN; WNK4 PROTEIN, HUMAN;

ALLOSTERISM; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIHYPERTENSIVE ACTIVITY; ARTICLE; CLINICAL EFFECTIVENESS; CONTROLLED STUDY; CRYSTAL STRUCTURE; DIASTOLIC BLOOD PRESSURE; DIURESIS; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENCY; ENZYME INHIBITION; GENE OVEREXPRESSION; HEMODYNAMIC PARAMETERS; HUMAN; HYPERTENSION; IN VIVO STUDY; KALIURESIS; MOUSE; NATRIURESIS; NONHUMAN; PHARMACOKINETIC PARAMETERS; PROCESS OPTIMIZATION; PROTEIN HOMEOSTASIS; RAT; SPONTANEOUSLY HYPERTENSIVE RAT; STRUCTURE ACTIVITY RELATION; SYSTOLIC BLOOD PRESSURE; ANIMAL; ANTAGONISTS AND INHIBITORS; HEK293 CELL LINE; MALE; METABOLISM; MOLECULAR DOCKING; SPRAGUE DAWLEY RAT; SYNTHESIS; TRANSGENIC MOUSE;

ALLOSTERIC REGULATION; ANIMALS; ANTIHYPERTENSIVE AGENTS; HEK293 CELLS; HUMANS; HYPERTENSION; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; MALE; MICE, TRANSGENIC; MINOR HISTOCOMPATIBILITY ANTIGENS; MOLECULAR DOCKING SIMULATION; PIPERAZINES; PROTEIN KINASE INHIBITORS; PROTEIN-SERINE-THREONINE KINASES; RATS, SPRAGUE-DAWLEY; STRUCTURE-ACTIVITY RELATIONSHIP; THIAZOLES;

EID: 85028626581     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.7b00708     Document Type: Article

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