(2R)-2-[(2-amino-5-sulfanyl[1,3]thiazolo[4,5-d]pyrimidin-7-yl)-amino]-4-methylpentan-1-ol | 463954-32-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (2R)-2-[(2-amino-5-sulfanyl[1,3]thiazolo[4,5-d]pyrimidin-7-yl)-amino]-4-methylpentan-1-ol
• 英文别名: (R)-2-(2-amino-5-mercaptothiazolo[4,5-d]pyrimidin-7-ylamino)-4-methylpentan-1-ol；(2R)-2-[(2-amino-5-mercapto[1,3]thiazolo[4,5-d]pyrimidin-7-yl)amino]-4-methylpentan-1-ol；(2R)-2-[[2-amino-5-mercapto[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]-4-methylpentan-1-ol；2-amino-7-[[(2R)-1-hydroxy-4-methylpentan-2-yl]amino]-4H-[1,3]thiazolo[4,5-d]pyrimidine-5-thione
• CAS: 463954-32-7
• 化学式: C₁₁H₁₇N₅OS₂
• 分子量: 299.421
• InChiKey: OGRDDYIZJRCWSP-ZCFIWIBFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  156
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R)-2-[(2-amino-5-sulfanyl[1,3]thiazolo[4,5-d]pyrimidin-7-yl)-amino]-4-methylpentan-1-ol 在 盐酸 、 sodium nitrite 作用下， 以 水 、 乙腈 为溶剂， 反应 18.0h， 以80%的产率得到(2R)-2-{2-chloro-5-[2-chloro-7-((1R)-1-hydroxymethyl-3-methyl-butylamino)-thiazolo[4,5-d]pyrimidin-5-yldisulfanyl]-thiazolo[4,5-d]pyrimidin-7-ylamino}-4-methyl-pentan-1-ol
  参考文献：
  名称：

  [EN] NEW 2-SUBSTITUTED, 4-AMINO-THIAZOLO[4,5-D] PYRIMIDINES, USEFUL AS CHEMOKINE RECEPTOR ANTAGONISTS, ESP. CX3CR1
  [FR] NOUVELLES 4-AMINO-THIAZOLO[4,5-D] PYRIMIDINES SUBSTITUEES EN 2, UTILES COMME ANTAGONISTES DU RECEPTEUR CHIMIOKINE, NOTAMMENT CX3CR1

  摘要：

  已披露了化合物的新型结构，其化学式为(I)，其中A、R1、R2、R3和X如规范中所定义，以及其药用盐，以及它们的制备方法、包含它们的药物组合物以及它们在治疗中的应用。化合物的化学式(I)是CX3CR1受体拮抗剂，因此在神经退行性疾病、脱髓鞘疾病、动脉粥样硬化和疼痛的治疗或预防中特别有用。

  公开号：

  WO2005033115A1
• 作为产物：
  描述：

  2-amino-5-[(phenylmethyl)thio]thiazolo[4,5-d]pyrimidin-7(4H)-one 在 N-甲基吡咯烷酮 、 氨 、 sodium 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 水 、 N,N-二甲基苯胺 为溶剂， 反应 3.0h， 生成 (2R)-2-[(2-amino-5-sulfanyl[1,3]thiazolo[4,5-d]pyrimidin-7-yl)-amino]-4-methylpentan-1-ol
  参考文献：
  名称：

  Substituted 7-Amino-5-thio-thiazolo[4,5-d]pyrimidines as Potent and Selective Antagonists of the Fractalkine Receptor (CX₃CR1)

  摘要：

  We have developed two parallel series, A and B, of CX(3)CR1 antagonists for the treatment of multiple sclerosis. By modifying the substituents on the 7-amino-5-thio-thiazolo[4,5-d]-pyrimidine core structure, we were able to achieve compounds with high selectivity for CX(3)CR1 over the closely related CXCR2 receptor. The structure-activity relationships showed that a leucinol moiety attached to the core-structure in the 7-position together with alpha-methyl branched benzyl derivatives in the 5-position displayed promising affinity, and selectivity as well as physicochemical properties, as exemplified by compounds 18a and 24h. We show the preparation of the first potent and selective orally available CX(3)CR1 antagonists.

  DOI：

  10.1021/jm3012273

文献信息

• [EN] NEW 2-SUBSTITUTED, 4-AMINO-THIAZOLO[4,5-D] PYRIMIDINES, USEFUL AS CHEMOKINE RECEPTOR ANTAGONISTS, ESP. CX3CR1<br/>[FR] NOUVELLES 4-AMINO-THIAZOLO[4,5-D] PYRIMIDINES SUBSTITUEES EN 2, UTILES COMME ANTAGONISTES DU RECEPTEUR CHIMIOKINE, NOTAMMENT CX3CR1
  申请人：ASTRAZENECA AB

  公开号：WO2005033115A1

  公开（公告）日：2005-04-14

  There are disclosed novel compounds of formula (I) wherein A, R1, R2, R3 and X are as defined in the specification, and pharmaceutically acceptable salts thereof, together with processes for their preparation, pharmaceutical compositions comprising them and their use in therapy. The compounds of formula (I) are CX3CR1 receptor antagonists and are thereby particularly useful in the treatment or prophylaxis of neurodegenerative disorders, demyelinating disease, atherosclerosis and pain.

  已披露了化合物的新型结构，其化学式为(I)，其中A、R1、R2、R3和X如规范中所定义，以及其药用盐，以及它们的制备方法、包含它们的药物组合物以及它们在治疗中的应用。化合物的化学式(I)是CX3CR1受体拮抗剂，因此在神经退行性疾病、脱髓鞘疾病、动脉粥样硬化和疼痛的治疗或预防中特别有用。
• [EN] RADIOFLUORINATED 7-AMINO-5-THIO-THIAZOLO[4,5-D]PYRIMIDINES FOR IMAGING FRACTALKINE RECEPTOR (CX3CR1)<br/>[FR] 7-AMINO-5-THIO-THIAZOLO[4,5-D]PYRIMIDINES RADIOFLUORÉES À UTILISER POUR IMAGER UN RÉCEPTEUR DE LA FRACTALKINE (CX3CR1)
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2016200939A1

  公开（公告）日：2016-12-15

  Radiofluorinated 7-Amino-5-thio-thiazolo[4,5-d]pyrimidines targeting Fractalkine Receptor (CX3CR1) are disclosed. Methods of imaging CX3CR1-expressing tumors or cells also are disclosed.

  揭示了针对Fractalkine受体（CX3CR1）的放射性氟化7-氨基-5-硫代噻唑并咪啉[4,5-d]嘧啶类化合物。还公开了用于成像CX3CR1表达的肿瘤或细胞的方法。
• Multiple labeling of a potent CX₃CR1 antagonist for the treatment of multiple sclerosis
  作者：Jonas Malmquist、Peter Ström

  DOI：10.1002/jlcr.2958

  日期：2012.8

  Several methods for the preparation of five isotopologues of the CX3CR1 antagonist 1 were developed. Volatile and radioactive 1-chloro- and 1-bromo-ethyl-benzene was handled in [2′-14C] and [3′, 5′-3H] labeling of 1. d-Leucinol ((R)-2-amino-4-methylpentan-1-ol) was labeled as [1-14C] and [4-14C] via a Wittig reaction using Garner's aldehyde and a Strecker amino acid synthesis with d-acylase resolvation, respectively. A [2H10]d-leucinol was used for the stable labeled [M + 10] isotopologue. The products were isolated with 97.6–100% stereo chemical and radiochemical purity as for specific activity 768 GBq/mmol and 1.6–2.0 GBq/mmol, respectively.

  开发了几种制备 CX3CR1 拮抗剂 1 的五种同位素异体物的方法。挥发性和放射性 1-氯- 和 1-溴-乙基-苯在 1. d-亮氨醇 ((R)-2-amino- 4-甲基戊-1-醇）分别通过使用 Garner 醛的 Wittig 反应和使用 d-酰基酶拆分的 Strecker 氨基酸合成标记为 [1-14C] 和 [4-14C]。 [2H10]d-亮氨醇用于稳定标记的[M + 10]同位素体。分离出的产物的立体化学纯度和放射化学纯度分别为 97.6–100%，比活度分别为 768 GBq/mmol 和 1.6–2.0 GBq/mmol。
• Novel use
  申请人：——

  公开号：US20040106628A1

  公开（公告）日：2004-06-03

  There is disclosed the use of a compound of formula (I) wherein R 1 , R 2 , R 3 , Ar and X are as defined in the specification, and pharmaceutically acceptable salts, enantiomers or racemates thereof, in the manufacture of a medicament, for the treatment or prophylaxis of diseases or conditions in which antagonism of the CX 3 CR1 receptor is beneficial. Certain novel compounds of formula (Ia) and pharmaceutically acceptable salts thereof, and enantiomers and racemates thereof are disclosed, together with processes for their preparation. The compounds of the formulae (I) and (Ia) are CX 3 CR1 receptor antagonists and are thereby particularly useful in the treatment or prophylaxis of neurodegenerative disorders, demyclinating disease and pain.

  本发明公开了使用式(I)中R1、R2、R3、Ar和X如规范中所定义的化合物及其药学上可接受的盐、对映体或外消旋体制备药物，用于治疗或预防CX3CR1受体拮抗作用有益的疾病或病况。公开了式(Ia)的某些新型化合物及其药学上可接受的盐、对映体和外消旋体，以及它们的制备方法。式(I)和(Ia)的化合物是CX3CR1受体拮抗剂，因此在神经退行性疾病、脱髓鞘疾病和疼痛的治疗或预防中特别有用。
• Novel Compounds 480
  申请人：Johansson Rolf

  公开号：US20080318981A1

  公开（公告）日：2008-12-25

  There are disclosed novel 5,7-disubstituted [1,3]thiazolo[4,5-d]pyrimidin-2(3H)-one derivatives of formula (I) wherein R 1 , R 2 , R 3 , R 4 and n are as defined in the specification, and pharmaceutically acceptable salts thereof, together with processes for their preparation, pharmaceutical compositions comprising them and their use in therapy. The compounds of formula (I) are CX 3 CR 1 receptor antagonists and are thereby particularly useful in the treatment or prophylaxis of neurodegenerative disorders, demyelinating disease, cardio- and cerebrovascular atherosclerotic disorders, peripheral artery disease, rheumatoid arthritis, pulmonary diseases such as COPD, asthma or pain.

  本发明公开了一种新型的5,7-二取代[1,3]噻唑并[4,5-d]嘧啶-2(3H)-酮衍生物(I)，其中R1、R2、R3、R4和n在规范中定义，以及其药学上可接受的盐，以及它们的制备方法、含有它们的制药组合物和它们在治疗中的应用。化合物(I)是CX3CR1受体拮抗剂，因此在治疗或预防神经退行性疾病、脱髓鞘疾病、心血管和脑血管动脉粥样硬化性疾病、周围动脉疾病、类风湿性关节炎、COPD、哮喘或疼痛方面特别有用。