methyl 4-hydroxylcinnoline-3-carboxylate | 17762-13-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: methyl 4-hydroxylcinnoline-3-carboxylate
• 英文别名: 4-Hydroxy-cinnolin-3-carbonsaeuremethylester；4-oxo-1,4-dihydro-cinnoline-3-carboxylic acid methyl ester；methyl 4-hydroxycinnoline-3-carboxylate；4-Hydroxy-cinnoline-3-carboxylic acid, methyl ester；methyl 4-oxo-1H-cinnoline-3-carboxylate
• CAS: 17762-13-9
• 化学式: C₁₀H₈N₂O₃
• 分子量: 204.185
• InChiKey: RVNSWWNJUGEWOR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  67.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 4-hydroxylcinnoline-3-carboxylate 在 氯化亚砜 作用下， 反应 2.5h， 生成 methyl 4-chlorocinnoline-3-carboxylate
  参考文献：
  名称：

  [EN] IMMUNOMODULATING HETEROCYCLIC COMPOUNDS
  [FR] COMPOSES HETEROCYCLIQUES D'IMMUNOMODULATION

  摘要：

  化合物的化学式(I)是CD80的抑制剂，在免疫调节疗法中具有用途：其中R1和R3分别代表H; F; CI; Br; -NO2; -CN; 通过F或Cl取代的C1-C6烷基; 或通过F取代的C1-C6烷氧基; R4代表羧酸基(-COOH)或其酯，或-C(=O)NR6R7，-NR7C(=O)R6，-NR7C(=O)OR6，-NHC(=O)NR7R6或-NHC(=S)NR7R6其中R6代表H，或化学式-(Alk)m-Q的基团，其中m为0或1，Alk是一个可选择取代的直链或支链C1-C12烷基，或C2-C12烯基，或C2-C12炔基基团或双价C3-C12碳环基团，其中任何一个基团可能包含一个或多个-O-，-S-或-N(R8)-键，其中R8代表H或C1-C4烷基，C3-C4烯基，C3-C4炔基，或C3-C6环烷基，而Q代表H; -NR9R10其中R9和R10独立地代表H; C1-C4烷基; C3-C4烯基; C3-C4炔基; C3-C6环烷基; 酯基; 可选择取代的碳环或杂环基团; 或当R9和R10与它们连接的氮一起形成一个环时，该环是可选择取代的; R7代表H或C1-C6烷基; 或当R6和R7与它们连接的原子一起形成一个可选择取代的含有5、6或7个环原子的单环杂环环，X代表一个键或化学式-(Z)n-(Alk)-或-(Alk)-(Z)n-其中Z代表-O-，-S-或-NH-，Alk如R6所定义，n为0或1。

  公开号：

  WO2004081011A1
• 作为产物：
  描述：

  2-(苯基亚肼基)丙二酸 在 氯化亚砜 、 四氯化钛 作用下， 以 氯仿 、 1,2-二氯乙烷 为溶剂， 反应 6.5h， 生成 methyl 4-hydroxylcinnoline-3-carboxylate
  参考文献：
  名称：

  正电子发射断层扫描成像人CD80的小分子的合成和结构亲和关系。

  摘要：

  共刺激分子CD80是免疫激活的早期标记。它在活化的抗原呈递细胞上调。我们旨在开发一种通过正电子发射断层扫描（PET）对CD80成像的示踪剂。合成了新型CD80配体，并通过SPR测试了对人CD80（hCD80）的亲和力和内源性配体的置换。几种化合物以1纳摩尔的亲和力与hCD80结合，并以纳摩尔浓度取代了CTLA-4和CD28。结构亲和关系研究揭示了与hCD80的强亲和力相关的部分，以及进一步修饰的位置。铅化合物MT107（7f）被碳11放射性标记。在体外，[11C] MT107显示出与hCD80阳性组织的特异性结合和高血浆蛋白结合。在体内，[11C] MT107积累在肝脏，胆囊，和肠道，但很少出现在hCD80阳性异种移植物中。高血浆蛋白结合和广泛的胆汁排泄可能导致不利的体内性能。

  DOI：

  10.1021/acs.jmedchem.9b00858

文献信息

• Cinnoline-carboxamides and process for their preparation
  申请人：Farmitalia Carlo Erba s.r.l.

  公开号：US04826837A1

  公开（公告）日：1989-05-02

  The invention relates to compounds having the general formula (I) ##STR1## wherein n is zero, 1 or 2; each of R.sub.1 and R.sub.2 is independently: (a) hydrogen, halogen, trifluoromethyl or C.sub.1 -C.sub.6 alkyl; (b) hydroxy, C.sub.1 -C.sub.6 alkoxy or C.sub.3 -C.sub.4 alkenyloxy; (c) nitro, amino, formylamino or C.sub.2 -C.sub.8 alkanoylamino; R.sub.3 represents hydrogen or C.sub.1 -C.sub.8 alkyl; R.sub.4 is: (a') C.sub.1 -C.sub.20 alkyl, unsubstituted or substituted by ##STR2## wherein each of R.sub.a and R.sub.b is independently phenyl or C.sub.1 -C.sub.6 alkyl, or R.sub.a and R.sub.b, taken together with the nitrogen atom to which they are linked, form a N-pyrrolidinyl, N-piperazinyl, hexahydroazepin-1-yl, thiomorpholino, morpholino or piperidino ring, wherein said heterocyclic rings may be unsubstituted or substituted by C.sub.1 -C.sub.6 alkyl or phenyl; (b') C.sub.5 -C.sub.10 cycloalkyl, unsubstituted or substituted by methyl; (c') 2- or 3-pyrrolidinyl, piperidyl of 2-piperazinyl, wherein said heterocyclic rings may be unsubstituted or substituted by C.sub.1 -C.sub.6 alkyl; (d') isoxazolyl or thiazolyl, wherein said heterocyclic rings may be unsubstituted or substituted by C.sub.1 -C.sub.6 alkyl; (e') pyridyl, unsubstituted or substituted by one or two substituents chosen independently from halogen, C.sub.1 -C.sub.6 alkyl and C.sub.1 -C.sub.6 alkoxy; or (f') phenyl, unsubstituted or substituted by one or two substituents chosen independently from halogen, CF.sub.3,C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, amino, nitro, formylamino and C.sub.2 -C.sub.8 alkanoylamino, and the pharmaceutically acceptable salts thereof, which possess immunomodulating activity and are useful e.g. in the treatment of neoplastic diseases and acute and chronic infections of both bacterial and viral origin in mammals.

  本发明涉及具有通式(I)的化合物 ##STR1## 其中n为0、1或2；每个R1和R2独立地为：(a)氢、卤素、三氟甲基或C1-C6烷基；(b)羟基、C1-C6烷氧基或C3-C4烯氧基；(c)硝基、氨基、甲酰氨基或C2-C8烷酰氨基；R3代表氢或C1-C8烷基；R4为：(a')C1-C20烷基，未被取代或被##STR2##取代，其中每个Ra和Rb独立地为苯基或C1-C6烷基，或者Ra和Rb与它们所连接的氮原子一起形成N-吡咯烷基、N-哌嗪基、六氢氮杂环庚三烯-1-基、硫代吗啉基、吗啉基或哌啶基环，其中所述杂环环可未被取代或被C1-C6烷基或苯基取代；(b')C5-C10环烷基，未被取代或被甲基取代；(c')2-或3-吡咯烷基、哌啶基或2-哌嗪基，其中所述杂环环可未被取代或被C1-C6烷基取代；(d')异噁唑基或噻唑基，其中所述杂环环可未被取代或被C1-C6烷基取代；(e')吡啶基，未被取代或被一个或两个独立地选自卤素、C1-C6烷基和C1-C6烷氧基的取代基取代；或(f')苯基，未被取代或被一个或两个独立地选自卤素、CF3、C1-C6烷基、C1-C6烷氧基、氨基、硝基、甲酰氨基和C2-C8烷酰氨基的取代基取代，以及其药学上可接受的盐，它们具有免疫调节活性，并且例如在治疗哺乳动物的肿瘤疾病以及由细菌和病毒引起的急性和慢性感染方面有用。
• Immunomodulating Heterocyclic Compounds
  申请人：Matthews Richard Ian

  公开号：US20080045527A1

  公开（公告）日：2008-02-21

  Compounds of formula (I) are inhibitors of CD80 and useful in immunomodulation therapy: wherein R 1 and R 3 independently represent H; F; Cl; Br; —NO 2 ; —CN; C 1 -C 6 alkyl optionally substituted by F or Cl; or C 1 -C 6 alkoxy optionally substituted by F; R 4 represents a carboxylic acid group (—COOH) or an ester thereof, or —C(═O)NR 6 R 7 , —NR 7 C(═O)R 6 , —NR 7 C(═O)OR 6 , —NHC(═O)NR 7 R 6 or —NHC(═S)NR 7 R 6 wherein R 6 represents H, or a radical of formula -(Alk) m -Q wherein m is 0 or 1, Alk is an optionally substituted divalent straight or branched C 1 -C 12 alkylene, or C 2 -C 12 alkenylene, or C 2 -C 12 alkynylene radical or a divalent C 3 -C 12 carbocyclic radical, any of which radicals may contain one or more —O—, —S— or —N(R 8 )— links wherein R 8 represents H or C 1 -C 4 alkyl, C 3 -C 4 alkenyl, C 3 -C 4 alkynyl, or C 3 -C 6 cycloalkyl, and Q represents H; —NR 9 R 10 wherein R 9 and R 10 independently represents H; C 1 -C 4 alkyl; C 3 -C 4 alkenyl; C 3 -C 4 alkynyl; C 3 -C 6 cycloalkyl; an ester group; an optionally substituted carbocyclic or heterocyclic group; or R 9 and R 10 form a ring when taken together with the nitrogen to which they are attached, which ring is optionally substituted; and R 7 represents H or C 1 -C 6 alkyl; or when taken together with the atom or atoms to which they are attached R 6 and R 7 form an optionally substituted monocyclic heterocyclic ring having 5, 6 or 7 ring atoms; and X represents a bond or a divalent radical of formula -(Z) n -(Alk)- or -(Alk)-(Z) n - wherein Z represents —O—, —S— or —NH—, Alk is as defined in relation to R 6 and n is 0 or 1.

  式（I）的化合物是CD80的抑制剂，可用于免疫调节治疗：其中R1和R3分别表示H; F; Cl; Br; -NO2; -CN; C1-C6烷基，其可选地被F或Cl取代; 或C1-C6烷氧基，其可选地被F取代; R4表示羧酸基（-COOH）或其酯，或-C（=O）NR6R7，-NR7C（=O）R6，-NR7C（=O）OR6，-NHC（=O）NR7R6或-NHC（=S）NR7R6，其中R6表示H，或式-(Alk)m-Q的基团，其中m为0或1，Alk为可选地取代的二价直链或支链C1-C12烷基，或C2-C12烯基，或C2-C12炔基基团或二价C3-C12环烷基基团，其中任何基团都可以包含一个或多个-O-，-S-或-N（R8）-链接，其中R8表示H或C1-C4烷基，C3-C4烯基，C3-C4炔基，或C3-C6环烷基; Q表示H; -NR9R10，其中R9和R10独立地表示H; C1-C4烷基; C3-C4烯基; C3-C4炔基; C3-C6环烷基; 酯基; 可选地取代的碳环或杂环基团; 或者R9和R10与它们所连接的氮一起形成一个环，该环可选地被取代; R7表示H或C1-C6烷基; 或者当它们所连接的原子或原子与R6一起形成一个可选地取代的含5,6或7个环原子的单环杂环时; X表示键或式-(Z)n-(Alk)-或-(Alk)-(Z)n-的二价基团，其中Z表示-O-，-S-或-NH-，Alk如在关于R6的定义中所述，n为0或1。
• Immunomodulating heterocyclic compounds
  申请人：Medigene Limited

  公开号：US07276505B2

  公开（公告）日：2007-10-02

  Compounds of formula (I) are inhibitors of CD80 and useful in immunomodulation therapy: wherein R1 and R3 independently represent H; F; CI; Br; —NO2; —CN; C1-C6 alkyl optionally substituted by F or Cl; or C1-C6 alkoxy optionally substituted by F; R4 represents a carboxylic acid group (—COOH) or an ester thereof, or —C(═O)NR6R7, —NR7C(═O)R6, —NR7C(═O)OR6, —NHC(═O)NR7R6 or —NHC(═S)NR7R6 wherein R6 represents H, or a radical of formula -(Alk)m-Q wherein m is 0 or 1, Alk is an optionally substituted divalent straight or branched C1-C12 alkylene, or C2-C12 alkenylene, or C2-C12 alkynylene radical or a divalent C3-C12 carbocyclic radical, any of which radicals may contain one or more —O—, —S— or —N(R8)— links wherein R8, represents H or C1-C4 alkyl, C3-C4 alkenyl, C3-C4 alkynyl, or C3-C6 cycloalkyl, and Q represents H; —NR9R10 wherein R9 and R10 independently represents H; C1-C4 alkyl; C3-C4 alkenyl; C3-C4 alkynyl; C3-C6 cycloalkyl; an ester group; an optionally substituted carbocyclic or heterocyclic group; or R9 and R10 form a ring when taken together with the nitrogen to which they are attached, which ring is optionally substituted; and R7 represents H or C1-C6 alkyl; or when taken together with the atom or atoms to which they are attached R6 and R7 form an optionally substituted monocyclic heterocyclic ring having 5, 6 or 7 ring atoms; and X represents a bond or a divalent radical of formula -(Z)n-(Alk)- or -(Alk)-(Z)n-wherein Z represents —O—, —S— or —NH—, Alk is as defined in relation to R6, and n is 0 or 1

  式(I)的化合物是CD80的抑制剂，用于免疫调节治疗：其中R1和R3分别表示H; F; CI; Br; -NO2; -CN; C1-C6烷基，其可选择地被F或Cl取代; 或C1-C6烷氧基，其可选择地被F取代; R4表示羧酸基（-COOH）或其酯，或-C（═O）NR6R7，-NR7C（═O）R6，-NR7C（═O）OR6，-NHC（═O）NR7R6或-NHC（═S）NR7R6，其中R6表示H，或者是式（Alk）m-Q的基团，其中m为0或1，Alk是一个可选择地取代的二价直链或支链C1-C12烷基，或C2-C12烯基，或C2-C12炔基基团或二价C3-C12碳环基团，其中任何一个基团都可能包含一个或多个-O-，-S-或-N（R8）-链，其中R8表示H或C1-C4烷基，C3-C4烯基，C3-C4炔基或C3-C6环烷基，而Q表示H; -NR9R10，其中R9和R10独立表示H; C1-C4烷基; C3-C4烯基; C3-C4炔基; C3-C6环烷基; 酯基; 可选择地取代的碳环或杂环基团; 或R9和R10与它们所连接的氮一起形成一个环，该环是可选择地取代的; 而R7表示H或C1-C6烷基; 或者当它们与所连接的原子或原子一起被取为一起时，R6和R7形成一个可选择地取代的单环杂环，其中有5、6或7个环原子; 而X表示键或式-(Z)n-(Alk)-或-(Alk)-(Z)n-的二价基团，其中Z表示-O-，-S-或-NH-，Alk的定义与R6有关，n为0或1。
• IMMUNOMODULATING HETEROCYCLIC COMPOUNDS
  申请人：Avidex Limited

  公开号：EP1603917A1

  公开（公告）日：2005-12-14
• US7276505B2
  申请人：——

  公开号：US7276505B2

  公开（公告）日：2007-10-02