(S)-N-(3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropyl)methanesulfonamide | 1025766-71-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (S)-N-(3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropyl)methanesulfonamide
• 英文别名: N-[(3S)-3-[1-(4-fluorophenyl)indazol-5-yl]-2,2-dimethyl-3-phenylpropyl]methanesulfonamide
• CAS: 1025766-71-5
• 化学式: C₂₅H₂₆FN₃O₂S
• 分子量: 451.565
• InChiKey: IRCRODKZEYCYNF-DEOSSOPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  72.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  在 吡啶 、 lithium aluminium tetrahydride 、 三聚氟氰 、 氨 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 21.0h， 生成 (S)-N-(3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropyl)methanesulfonamide
  参考文献：
  名称：

  Synthesis and structure–activity relationships of novel indazolyl glucocorticoid receptor partial agonists

  摘要：

  SAR was used to further develop an indazole class of non-steroidal glucocorticoid receptor agonists aided by a GR LBD (ligand-binding domain)-agonist co-crystal structure described in the accompanying paper. Progress towards discovering a dissociated GR agonist guided by human in vitro assays biased the optimization of this compound series towards partial agonists that possessed excellent selectivity against other nuclear hormone receptors. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.06.085

文献信息

• MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-kB ACTIVITY AND USE THEREOF
  申请人：Sheppeck James E.

  公开号：US20100075961A1

  公开（公告）日：2010-03-25

  Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-κB activity including inflammatory and immune diseases, obesity and diabetes having the structure of formula (I), its enantiomers, diastereomers, or a pharmaceutically acceptable salt, or hydrate, thereof, wherein X is (Ia); or X is (Ib); or X is (Ic); (Id) is heterocycle or heteroaryl; E is —N—, —NR 1 —, —O—, —S—, —SO 2 — or —CR 2 —; F is —N—, —NR 1a —, —O—, —S—, —SO 2 — or —CR 2a —; G is N, —NR 1b —, —O—, —S—, —SO 2 — or —CR 2b —, provided that the E-F-G containing heterocyclic ring formed does not contain a S—S or S—O bond, and at least one of E, F and G is a heteroatom; J, J a , M, M a , Q, R x , R y , R 1 , R 1a , R 1b , R 2 , R 2a , R 2b , and R 3 to R 21 , Z, Z a , Z b , and Z c are as defined above.

  提供了一种新型的非类固醇化合物，其结构式（I）及其对映异构体、二对映异构体或其药学上可接受的盐或水合物，可用于治疗与糖皮质激素受体、AP-1和/或NF-κB活性调节相关的疾病，包括炎症和免疫性疾病、肥胖和糖尿病，其中X为（Ia）; 或X为（Ib）; 或X为（Ic）; （Id）为杂环或杂芳基; E为—N—、—NR1—、—O—、—S—、—SO2—或—CR2—; F为—N—、—NR1a—、—O—、—S—、—SO2—或—CR2a—; G为N、—NR1b—、—O—、—S—、—SO2—或—CR2b—，但E、F和G中含有的杂环环不含有S—S或S—O键，且E、F和G中至少有一个是杂原子; J、Ja、M、Ma、Q、Rx、Ry、R1、R1a、R1b、R2、R2a、R2b和R3到R21、Z、Za、Zb和Zc的定义如上所述。
• WO2008/57857
  申请人：——

  公开号：——

  公开（公告）日：——
• US8198311B2
  申请人：——

  公开号：US8198311B2

  公开（公告）日：2012-06-12
• [EN] MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-?B ACTIVITY AND USE THEREOF<br/>[FR] MODULATEURS DU RÉCEPTEUR DES GLUCOCORTICOÏDES ET DE L'ACTIVITÉ DE AP-1 ET / OU DE NF-?B ET UTILISATION DESDITS MODULATEURS
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2008057857A1

  公开（公告）日：2008-05-15

  [EN] Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-?B activity including inflammatory and immune diseases, obesity and diabetes having the structure of formula (I), its enantiomers, diastereomers, or a pharmaceutically acceptable salt, or hydrate, thereof, wherein X is (Ia); or X is (Ib); or X is (Ic); (Id) is heterocycle or heteroaryl; E is -N-, -NR₁-, -O-, -S-, -SO₂- or -CR₂-; F is -N-, -NR_1a-, -O-, -S-, SO₂- or -CR_2a-; G is N, -NR_1b-, -O-, -S-, SO₂- or -CR_2b-, provided that the E-F-G containing heterocyclic ring formed does not contain a S-S or S-O bond, and at least one of E, F and G is a heteroatom; J, J_a, M, M_a, Q, R_x, R_y, R₁, R_1a, R_1b, R₂, R_2a, R_2b, and R₃ to R₂₁, Z, Z_a, Z_b, and Z_c are as defined above.
  [FR] Nouveaux composés non stéroïdiens qui sont utiles pour traiter des maladies associées à la modulation du récepteur des glucocorticoïdes et / ou de l'activité de AP-1 et / ou de l'activité de NF-?B, dont les maladies inflammatoires et auto-immunes, l'obésité et le diabète, et qui présentent la structure de formule (I), leurs énantiomères, leurs diastéréomères ou un sel ou hydrate de qualité pharmaceutique desdits composés. Dans la formule (I), X représente (Ia); ou X représente (Ib); ou X représente (Ic); (Id) représente un hétérocycle ou hétéroaryle, E représente -N-, -NR₁-, -O-, -S-, -SO₂- ou -CR₂-; F représente -N-, -NR_1a-, -O-, -S-, SO₂- ou -CR_2a-; G représente N, -NR_1b-, -O-, -S-, SO₂- or -CR_2b-, à condition que le noyau hétérocyclique formé contenant E-F-G ne contienne pas de liaison S-S ou S-O, et qu'au moins E et / ou F et / ou G soit un hétéroatome; et J, Ja, M, M_a, Q, R_x, R_y, R₁, R_1a, R_1b, R₂, R_2a, R_2b et R₃ à R₂₁, Z, Z_a, Z_b et Z_c soient tels que définis dans le descriptif.
• Synthesis and structure–activity relationships of novel indazolyl glucocorticoid receptor partial agonists
  作者：John L. Gilmore、James E. Sheppeck、Jim Wang、T.G. Murali Dhar、Cullen Cavallaro、Arthur M. Doweyko、Lorraine Mckay、Mark D. Cunningham、Sium F. Habte、Steven G. Nadler、John H. Dodd、John E. Somerville、Joel C. Barrish

  DOI：10.1016/j.bmcl.2013.06.085

  日期：2013.10

  SAR was used to further develop an indazole class of non-steroidal glucocorticoid receptor agonists aided by a GR LBD (ligand-binding domain)-agonist co-crystal structure described in the accompanying paper. Progress towards discovering a dissociated GR agonist guided by human in vitro assays biased the optimization of this compound series towards partial agonists that possessed excellent selectivity against other nuclear hormone receptors. (C) 2013 Elsevier Ltd. All rights reserved.