3-氧代-3,4-二氢-2H-苯并[B][1,4]噁嗪-5-羧酸 | 483282-25-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 中文名称: 3-氧代-3,4-二氢-2H-苯并[B][1,4]噁嗪-5-羧酸
• 英文名称: 3-oxo-3,4-dihydro-2H-benzo[1,4]oxazine-5-carboxylic acid
• 英文别名: 3-Oxo-3,4-dihydro-2h-benzo[b][1,4]oxazine-5-carboxylic acid；3-oxo-4H-1,4-benzoxazine-5-carboxylic acid
• CAS: 483282-25-3
• 化学式: C₉H₇NO₄
• 分子量: 193.159
• InChiKey: OCBVWXXCVFAUBS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  3-氧代-3,4-二氢-2H-苯并[B][1,4]噁嗪-5-羧酸 、 (S)-ethyl 4-amino-6-bromospiro[chroman-2,4'-piperidine]-1'-carboxylate hydrochloride 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 ethyl (S)-6-bromo-4-(3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-5-carboxamido)spiro[chromane-2,4'-piperidine]-1'-carboxylate
  参考文献：
  名称：

  DNA-Encoded Library Technology-Based Discovery, Lead Optimization, and Prodrug Strategy toward Structurally Unique Indoleamine 2,3-Dioxygenase-1 (IDO1) Inhibitors

  摘要：

  We report the discovery of a novel indoleamine 2,3-dioxygenase-1 (IDO1) inhibitor class through the affinity selection of a previously unreported indole-based DNA-encoded library (DEL). The DEL exemplar, spiro-chromane 1, had moderate IDO1 potency but high in vivo clearance. Series optimization quickly afforded a potent, low in vivo clearance lead 11. Although amorphous 11 was highly bio-available, crystalline 11 was poorly soluble and suffered disappointingly low bio-availability because of solubility-limited absorption. A prodrug approach was deployed and proved effective in discovering the highly bio-available phosphonooxymethyl 31, which rapidly converted to 11 in vivo. Obtaining crystalline 31 proved problematic, however; thus salt screening was performed in an attempt to circumvent this obstacle and successfully delivered greatly soluble and bio-available crystalline tris-salt 32. IDO1 inhibitor 32 is characterized by a low calculated human dose, best-in-class potential, and an unusual inhibition mode by binding the IDO1 heme-free (apo) form.

  DOI：

  10.1021/acs.jmedchem.9b01799
• 作为产物：
  描述：

  methyl 3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-5-carboxylate 在 sodium hydroxide 作用下， 反应 4.0h， 生成 3-氧代-3,4-二氢-2H-苯并[B][1,4]噁嗪-5-羧酸
  参考文献：
  名称：

  苯并恶唑酮的合理设计，合成及构效关系：基于芬诺苯姆结构的新型有效mglu5受体拮抗剂。

  摘要：

  通过将来自高通量筛选活动的信息与已知的抗焦虑性芬巴胺的结构相结合，开发出了一类新型的有效且稳定的mGlu5受体拮抗剂。该类别的代表性化合物表现出有利的药代动力学性质，并且在体内焦虑模型中具有活性。

  DOI：

  10.1016/j.bmcl.2006.12.006

文献信息

• THIAZOLIDINE DERIVATIVES AS OREXIN RECEPTOR ANTAGONISTS
  申请人：Aissaoui Hamed

  公开号：US20100113531A1

  公开（公告）日：2010-05-06

  The invention relates to novel thiazolidine derivatives of the formula (I) wherein A and R 1 are as described in the description and their use as medicaments, especially as orexin receptor antagonists.

  本发明涉及式(I)的新噻唑啉衍生物，其中A和R1如描述中所述，以及它们作为药物的使用，尤其是作为食欲素受体拮抗剂的使用。
• Monoacylglycerol Lipase Modulators
  申请人：Janssen Pharmaceutica NV

  公开号：US20200102303A1

  公开（公告）日：2020-04-02

  Fused compounds of Formula (I) and Formula (II), pharmaceutical compositions containing them, methods of making them, and methods of using them including methods for treating disease states, disorders, and conditions associated with MGL modulation, such as those associated with pain, psychiatric disorders, neurological disorders (including, but not limited to major depressive disorder, treatment resistant depression, anxious depression, bipolar disorder), cancers and eye conditions. Wherein R 1 , R 2 , R 2a , R 3 , R 3a , R 4 , and R 4a are defined herein.

  化合物的结构式（I）和结构式（II），含有它们的药物组合物，制备它们的方法，以及使用它们的方法，包括用于治疗与MGL调节相关的疾病状态、紊乱和病况的方法，例如与疼痛、精神障碍、神经障碍（包括但不限于重性抑郁障碍、治疗抵抗性抑郁症、焦虑性抑郁症、躁郁症）、癌症和眼部疾病相关的方法。 其中R1、R2、R2a、R3、R3a、R4和R4a在此处定义。
• AZETIDINE COMPOUNDS AS OREXIN RECEPTOR ANTAGONISTS
  申请人：Aissaoui Hamed

  公开号：US20100222600A1

  公开（公告）日：2010-09-02

  The invention relates to novel azetidine compounds of formula (I), wherein R 1 , R 2 , and X are as described in the description and their use as orexin receptor antagonists.

  这项发明涉及一种新型的式(I)的氮杂环丙烷化合物，其中R1、R2和X如描述中所述，并且它们作为促进睡眠的药物受体拮抗剂的用途。
• [EN] THIAZOLIDINE COMPOUNDS AS OREXIN RECEPTOR ANTAGONISTS<br/>[FR] COMPOSÉS THIAZOLIDINES EN TANT QU'ANTAGONISTES DES RÉCEPTEURS DE L'OREXINE
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2010004507A1

  公开（公告）日：2010-01-14

  The invention relates to thiazolidine derivatives of the formula (I) wherein A, B, and R1 are as described in the description, to salts, especially pharmaceutically acceptable salts, of such compounds and to their use as medicaments, especially as orexin receptor antagonists.

  这项发明涉及式(I)的噻唑啉衍生物，其中A、B和R1如描述中所述，以及这些化合物的盐，特别是药学上可接受的盐，以及它们作为药物的用途，特别是作为促进睡眠的药物受体拮抗剂。
• 3-AZA-BICYCLO[3.1.0]HEXANE DERIVATIVES
  申请人：Aissaoui Hamed

  公开号：US20100016401A1

  公开（公告）日：2010-01-21

  The invention relates to 3-aza-bicyclo[3.1.0]hexane derivatives of formula (I) wherein A, B, n, X, and R 1 are as described in the description, and salts thereof, and their use as orexin receptor antagonists.

  这项发明涉及式(I)的3-aza-双环[3.1.0]己烷衍生物，其中A、B、n、X和R1如描述中所述，以及其盐，以及它们作为促进睡眠的荷尔蒙受体拮抗剂的用途。