2-benzyl-5-methyl-4-oxo-3H,4H-thieno[2,3-d]pyrimidine-6-carboxylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: 2-benzyl-5-methyl-4-oxo-3H,4H-thieno[2,3-d]pyrimidine-6-carboxylic acid
• 英文别名: 2-benzyl-5-methyl-4-oxo-3H-thieno[2,3-d]pyrimidine-6-carboxylic acid
• 化学式: C₁₅H₁₂N₂O₃S
• mdl: MFCD03030516
• 分子量: 300.338
• InChiKey: DMVRIOBFXVERIW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.133
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-benzyl-5-methyl-4-oxo-3H,4H-thieno[2,3-d]pyrimidine-6-carboxylic acid 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 生成 2-azidoethyl (5-acetamido-9-(2-benzyl-5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxamido)-3,5,9-trideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonic acid)-(2→3)-β-D-galactopyranosyl-(1→4)-2-acetamido-2-deoxy-β-Dglucopyranoside
  参考文献：
  名称：

  In Silico-Aided Design of a Glycan Ligand of Sialoadhesin for in Vivo Targeting of Macrophages

  摘要：

  Cell-specific delivery of therapeutic agents using ligand targeting is gaining interest because of its potential for increased efficacy and reduced side effects. The challenge is to develop a suitable ligand for a cell-surface receptor that is selectively expressed on the desired cell. Sialoadhesin (Sn, Siglec-1, CD169), a sialic acid-binding immunoglobulin-like lectin (Siglec) expressed on subsets of resident and inflammatory macrophages, is an attractive target for the development of a ligand-targeted delivery system. Here we report the development of a high-affinity and selective ligancl for Sn that is an analogue of the natural ligand and is capable of targeting liposomal nanoparticles to Sn-expressing cells in vivo. An efficient in silico screen of a library of similar to 8400 carboxylic acids was the key to identifying novel 9-N-acyl-substituted N-acetylneuramic acid (Neu5Ac) substituents as potential lead compounds. A small panel of targets were selected from the screen and synthesized to evaluate their affinities and selectivities. The most potent of these Sn ligands, (4H-thieno[3,2-c]chromene-2-carbamoyl)-Neu5Ac alpha 2-3Gal beta 1-4GlcNAc ((TCC)Neu5Ac), was conjugated to lipids for display on a liposomal nanoparticle for evaluation of targeted delivery to cells. The (TCC)Neu5Ac liposomes were found to target liposomes selectively to cells expressing either murine or human Sn in vitro, and when administered to mice, they exhibited in vivo targeting to Sn-positive macrophages.

  DOI：

  10.1021/ja307501e

文献信息

• A New One-Step Route for the Synthesis of Fused Pyrido[1,2-<i>a</i>]pyrimidin-4-ones
  作者：Dmitriy Volochnyuk、Andrey Plaskon、Sergey Ryabukhin、Andrey Tolmachev

  DOI：10.1055/s-2008-1066988

  日期：——

  variety of 2-methylpyrimidin-4(3 H)-ones promoted by chlorotrimethylsilane was investigated. A simple and flexible general procedure for the synthesis of a series of fused pyrido[1,2- A]pyrimidin-4-ones is proposed. A set of functionally and structurally diverse pyrido[1,2- A]pyrimidin-4-ones were obtained in high yields.

  研究了三甲基氯硅烷促进的3-甲酰色酮与多种2-甲基嘧啶-4(3 H)-酮的环化反应。提出了一种用于合成一系列稠合吡啶并[1,2-A]嘧啶-4-酮的简单灵活的通用程序。以高产率获得了一组功能和结构多样的吡啶并[1,2-A]嘧啶-4-酮。
• TREATING AGENT OF UROPATHY
  申请人：Gotanda Kotaro

  公开号：US20100113484A1

  公开（公告）日：2010-05-06

  Disclosed is a treating agent of overactive bladder syndrome, pollakiuria, urinary incontinence, dysuria in benign prostatic hyperplasia or urolithiasis, which comprises a compound having PDE9-inhibiting activity as the active ingredient.

  本发明涉及一种治疗过度活跃膀胱综合症、排尿频繁、尿失禁、良性前列腺增生或泌尿结石引起的排尿困难的治疗剂，其包含一种具有PDE9抑制活性的化合物作为活性成分。
• THIENOPYRIMIDINE DERIVATIVES
  申请人：GOTANDA Kotaro

  公开号：US20130023546A1

  公开（公告）日：2013-01-24

  This invention provides thienopyrimidine derivatives of the formula, wherein R 1 stands for hydrogen atom, an alkyl group or the like; R 2 stands for a hydrogen atom, an alkyl or amino group or the like, R 3 stands for an alkyl, alkenyl or alkylthio group or the like or a group Y—X—; or R 2 and R 3 may together form tetramethylene group; X standing for a direct bond or linking group such as CH 2 , CH(OH), S, O, NH; Y standing for a substituted or unsubstituted aromatic carbocycylic, aromatic heterocylic, cycloalkyl or saturated heterocyclic group or the like; Z stands for S or O, and n is 0 or an integer of 1 to 4, or salts thereof, which exhibit an inhibitory effect on PDE9, and are therefore useful for prevention or treatment of overactive bladder syndrome, pollakiuria, urinary incontinence, dysuria associated with prostatic hyperplasia, urolithiasis, Alzheimer's disease, chronic obstructive pulmonary disease, myocardial infarction, thrombosis, diabetes and the like.

  本发明提供了式子中的噻吩嘧啶衍生物，其中R1代表氢原子，烷基或类似物；R2代表氢原子，烷基或氨基基团或类似物，R3代表烷基，烯基或烷基硫基团或类似物或Y—X—基团；或者R2和R3可以形成四亚甲基基团；X代表直接键或连接基团，例如CH2，CH（OH），S，O，NH；Y代表取代或未取代的芳香环烷基，芳香杂环基，环烷基或饱和杂环基团或类似物；Z代表S或O，n为0或1到4的整数，或其盐。这些化合物在PDE9上具有抑制作用，因此可用于预防或治疗过度活动的膀胱综合症，尿频，尿失禁，前列腺增生症相关的排尿困难，泌尿结石，阿尔茨海默病，慢性阻塞性肺疾病，心肌梗死，血栓形成，糖尿病等。
• Thienopyrimidine Derivatives
  申请人：Gotanda Kotaro

  公开号：US20090203703A1

  公开（公告）日：2009-08-13

  This invention provides thienopyrimidine derivatives of the formula, wherein R 1 stands for hydrogen atom, an alkyl group or the like; R 2 stands for a hydrogen atom, an alkyl or amino group or the like, R 3 stands for an alkyl, alkenyl or alkylthio group or the like or a group Y—X—; or R 2 and R 3 may together form tetramethylene group; X standing for a direct bond or linking group such as CH 2 , CH(OH), S, O, NH; Y standing for a substituted or unsubstituted aromatic carbocycylic, aromatic heterocylic, cycloalkyl or saturated heterocyclic group or the like; Z stands for S or O, and n is 0 or an integer of 1 to 4, or salts thereof, which exhibit an inhibitory effect on PDE9, and are therefore useful for prevention or treatment of overactive bladder syndrome, pollakiuria, urinary incontinence, dysuria associated with prostatic hyperplasia, urolithiasis, Alzheimer's disease, chronic obstructive pulmonary disease, myocardial infarction, thrombosis, diabetes and the like.

  该发明提供了式子中的噻吩嘧啶衍生物，其中R1代表氢原子、烷基或类似基团；R2代表氢原子、烷基或氨基等基团，R3代表烷基、烯基或烷硫基等基团或Y—X—基团；或R2和R3可以共同形成四亚甲基基团；X代表直接键或连接基团，如CH2，CH（OH），S，O，NH；Y代表取代或未取代的芳香环烷基、芳香杂环基、环烷基或饱和杂环基等基团；Z代表S或O，n为0或1至4的整数，或其盐。这些衍生物对PDE9具有抑制作用，因此可用于预防或治疗过度活跃的膀胱综合症、尿频、尿失禁、前列腺增生引起的排尿困难、泌尿结石、阿尔茨海默病、慢性阻塞性肺疾病、心肌梗死、血栓形成、糖尿病等疾病。
• THERAPEUTIC AGENT FOR URINARY TRACT DISEASE
  申请人：ASKA Pharmaceutical Co., Ltd.

  公开号：EP2123301A1

  公开（公告）日：2009-11-25

  Disclosed is a treating agent of overactive bladder syndrome, pollakiuria, urinary incontinence, dysuria in benign prostatic hyperplasia or urolithiasis, which comprises a compound having PDE9-inhibiting activity as the active ingredient.

  本发明公开了一种治疗膀胱过度活动症、花粉尿症、尿失禁、良性前列腺增生症排尿困难或尿路结石的药物，其活性成分包括一种具有 PDE9 抑制活性的化合物。