(S)-3-amino-3-(3-((R)-1-amino-2-hydroxyethyl)-1,2,4-oxadiazol-5-yl)propanamide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-3-amino-3-(3-((R)-1-amino-2-hydroxyethyl)-1,2,4-oxadiazol-5-yl)propanamide
• 英文别名: (3S)-3-amino-3-[3-[(1R)-1-amino-2-hydroxyethyl]-1,2,4-oxadiazol-5-yl]propanamide
• 化学式: C₇H₁₃N₅O₃
• 分子量: 215.212
• InChiKey: GBRIVGUQMYWVTC-IMJSIDKUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.8
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  154
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  ((R)-1-(5-((S)-1-amino-3-keto-3-(tritylamino)propyl)-1,2,4-oxadiazol-3-yl)-2-(tert-butoxy)ethyl)carbamic acid tert-butyl ester 在 三异丙基硅烷 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 (S)-3-amino-3-(3-((R)-1-amino-2-hydroxyethyl)-1,2,4-oxadiazol-5-yl)propanamide
  参考文献：
  名称：

  [EN] 1,2,4-OXADIAZOLE DERIVATIVES AS IMMUNOMODULATORS
  [FR] DÉRIVÉS 1,2,4-OXADIAZOLE UTILISÉS COMME IMMUNOMODULATEURS

  摘要：

  本发明涉及一种作为治疗剂的1,2,4-噁二唑和1,2,4-噻二唑化合物，能够抑制程序性细胞死亡1（PD1）信号通路。该发明还涉及治疗剂的衍生物。该发明还包括使用所述治疗剂和其衍生物通过免疫增强治疗障碍，包括抑制由PD-1、PD-L1或PD-L2诱导的免疫抑制信号和使用它们的治疗方法。

  公开号：

  WO2015033299A1

文献信息

• 1,2,4-Oxadiazole Derivatives as Immunomodulators
  申请人：Sasikumar Pottayil Govindan Nair

  公开号：US20150073024A1

  公开（公告）日：2015-03-12

  The present invention relates to 1,2,4-oxadiazole and 1,2,4-thiadiazole compounds as therapeutic agents capable of inhibiting the programmed cell death 1 (PD1) signaling pathway. The invention also refers to derivatives of the therapeutic agents. The invention also encompasses the use of the said therapeutic agents and derivatives for treatment of disorders via immunopotentiation comprising inhibition of immunosuppressive signal induced due to PD-1, PD-L1, or PD-L2 and therapies using them.

  本发明涉及1,2,4-噁二唑和1,2,4-噻二唑化合物作为治疗剂，能够抑制程序性细胞死亡1（PD1）信号通路。本发明还涉及治疗剂的衍生物。本发明还涵盖使用所述治疗剂和衍生物通过免疫增强治疗免疫抑制信号（由于PD-1，PD-L1或PD-L2引起）诱导的疾病和治疗方法。
• 1,2,4-oxadiazole derivatives as immunomodulators
  申请人：Sasikumar Pottayil Govindan Nair

  公开号：US10173989B2

  公开（公告）日：2019-01-08

  The present invention relates to synthetic methods for 1,2,4-oxadiazole compounds. The general synthetic scheme is: R1 represents −CH2OtBu or −CH(CH3)OtBu, R3 represents −CH2C(O)NHCPh3, −CH2CH2C(O)NHCPh3, −CH2C(O)OtBu, or −CH2CH2C(O)OtBu, and Aaa is an amino acid residue selected from Thr and Ser; wherein the C-terminus thereof is esterified, and wherein the hydroxy moiety of the side chain of Thr or Ser is substituted with tbutyl; the base is triethylamine; and the solvent is tetrahydrofuran.

  本发明涉及 1,2,4-噁二唑化合物的合成方法。一般合成方案如下 R1代表-CH2OtBu或-CH(CH3)OtBu，R3代表-CH2C(O)NHCPh3、-CH2CH2C(O)NHCPh3、-CH2C(O)OtBu或-CH2CH2C(O)OtBu，Aaa是选自Thr和Ser的氨基酸残基；其中，C-末端被酯化，Thr 或 Ser 侧链的羟基被叔丁基取代；碱为三乙胺；溶剂为四氢呋喃。
• Reducing tumor burden by administering CCR1 antagonists in combination with PD-1 inhibitors or PD-L1 inhibitors
  申请人：CHEMOCENTRYX, INC.

  公开号：US10568870B2

  公开（公告）日：2020-02-25

  The present invention provides methods for reducing tumor burden, tumor growth, tumor progression, and/or metastasis in a subject suffering from a solid tumor cancer such as triple negative breast cancer. The methods include administering to a subject in need thereof a therapeutically effective amount of a PD-L1 inhibitor or a PD-1 inhibitor in combination with a small molecule chemokine receptor antagonist that blocks CCR1.

  本发明提供了减少实体瘤癌症如三阴性乳腺癌患者的肿瘤负担、肿瘤生长、肿瘤进展和/或转移的方法。这些方法包括向有需要的受试者施用治疗有效量的PD-L1抑制剂或PD-1抑制剂与阻断CCR1的小分子趋化因子受体拮抗剂。
• <i>In Vitro</i> Assessment of Putative PD-1/PD-L1 Inhibitors: Suggestions of an Alternative Mode of Action
  作者：Derek J. Blevins、Ronan Hanley、Trevor Bolduc、David A. Powell、Michael Gignac、Kayleigh Walker、Mark D. Carr、Fraser Hof、Jeremy E. Wulff

  DOI：10.1021/acsmedchemlett.9b00221

  日期：2019.8.8

  The programmed cell death protein 1 (PD-1) signaling axis is among the most important therapeutic targets in modern oncology. Aurigene Discovery Technologies Ltd. (Aurigene) has patented a series of peptidomimetic small molecules derived from the PD-1 protein sequence for use in targeting the interaction between PD-1 and its ligand, PD-L1. We evaluated three of Aurigenes most potent compounds in SPR binding assays. Our results showed that these compounds-each of which is known to be potently effective in a splenocyte recovery assay-do not directly inhibit the PD-1/PD-L1 interaction nor do they appear to bind to either of the constituent proteins, indicating that another mechanism is at play. As a result of these studies and upon consideration of structural features within the PD-1/PD-L1 complex, we hypothesize that the Aurigene molecules may interact with a currently unknown protein capable of regulating the PD-1 axis.
• 1,2,4-OXADIAZOLE DERIVATIVES AS IMMUNOMODULATORS
  申请人：Aurigene Discovery Technologies Limited

  公开号：EP3041827B1

  公开（公告）日：2018-04-18