2,5-dimethyl-4-chloropyridine N-oxide | 155919-09-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2,5-dimethyl-4-chloropyridine N-oxide
• 英文别名: 4-chloro-2,5-dimethylpyridine 1-oxide；4-chloro-2,5-dimethyl-pyridine 1-oxide；4-chloro-2,5-dimethyl-1-oxidopyridin-1-ium
• CAS: 155919-09-8
• 化学式: C₇H₈ClNO
• 分子量: 157.6
• InChiKey: WKOZZJRWYNIQJB-UHFFFAOYSA-N

物化性质

• 沸点：
  329.7±37.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  25.5
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2,5-dimethyl-4-chloropyridine N-oxide 在 氢氧化钾 、 potassium permanganate 、 硫酸 、 氢溴酸 、 硝酸 、 sodium carbonate 、 间氯过氧苯甲酸 、 三氯化磷 作用下， 以 甲醇 、 氯仿 、 水 为溶剂， 反应 76.5h， 生成 5-甲基-3-硝基-4-氧代-1,4-二氢-2-吡啶羧酸
  参考文献：
  名称：

  Toward the Design of an RNA:DNA Hybrid Binding Agent

  摘要：

  One characteristic function of the retroviruses, which is generally not found in normal eukaryotic cells, is production of a long RNA:DNA hybrid in the viral replication phase. If agents are designed which bind only to the RNA:DNA hybrid, but neither to DNA nor to RNA, such agents will be able to inhibit specifically the RNase H activity of retroviral reverse transcriptase, and therefore will suppress viral replication. Actinomycin D binds to double-stranded DNA, but not to RNA, because steric hindrance between the 2-amino group of the phenoxazinone ring and the 2'-hydroxyl group of RNA prevents intercalation of the antibiotic. However, if the C8-H in the phenoxazinone ring is replaced by an aromatic nitrogen N8, a strong hydrogen bond acceptor, this analog (N8-actinomycin D) might be able to bind intercalatively to an RNA:DNA hybrid by forming an additional hydrogen bond between N8 and the 2'-hydroxyl group of guanosine ribose. This hypothesis has been tested by a molecular mechanics calculation using a model structure of the complex between N8-actinomycin D and a small RNA:DNA hybrid, r(GC):d(GC). The results of the molecular mechanics calculation suggest that N8-actinomycin D can intercalatively bind to the RNA: DNA hybrid by making an additional intracomplex hydrogen bond. This hydrogen bonding capability of N8 has been confirmed in the crystal structure of the chromophore of N8-actinomycin D. Thus, N8-actinomycin D has been synthesized by coupling the pyridine and benzene fragments obtained independently. A binding study indicates that both actinomycin D and N8-actinomycin D bind intercalatively not only to DNA:DNA double strands but also to RNA:DNA hybrids. Although the overall binding capacity of N8-actinomycin D is reduced substantially in comparison with that of actinomycin D itself, N8-actinomycin D tends to bind relatively more favorably than actinomycin D to the RNA:DNA hybrids. Thus, this initial attempt at designing an RNA:DNA hybrid binding agent appears to be successful. However, it is necessary to modify the agent further to increase its RNA:DNA hybrid binding character and to decrease the DNA:DNA binding character, in order to make a useful RNA:DNA hybrid binding agent.

  DOI：

  10.1021/ja00085a002
• 作为产物：
  描述：

  2,5-二甲基吡啶 1-氧化物 在 硫酸 、 硝酸 、 乙酰氯 作用下， 反应 4.5h， 生成 2,5-dimethyl-4-chloropyridine N-oxide
  参考文献：
  名称：

  Toward the Design of an RNA:DNA Hybrid Binding Agent

  摘要：

  One characteristic function of the retroviruses, which is generally not found in normal eukaryotic cells, is production of a long RNA:DNA hybrid in the viral replication phase. If agents are designed which bind only to the RNA:DNA hybrid, but neither to DNA nor to RNA, such agents will be able to inhibit specifically the RNase H activity of retroviral reverse transcriptase, and therefore will suppress viral replication. Actinomycin D binds to double-stranded DNA, but not to RNA, because steric hindrance between the 2-amino group of the phenoxazinone ring and the 2'-hydroxyl group of RNA prevents intercalation of the antibiotic. However, if the C8-H in the phenoxazinone ring is replaced by an aromatic nitrogen N8, a strong hydrogen bond acceptor, this analog (N8-actinomycin D) might be able to bind intercalatively to an RNA:DNA hybrid by forming an additional hydrogen bond between N8 and the 2'-hydroxyl group of guanosine ribose. This hypothesis has been tested by a molecular mechanics calculation using a model structure of the complex between N8-actinomycin D and a small RNA:DNA hybrid, r(GC):d(GC). The results of the molecular mechanics calculation suggest that N8-actinomycin D can intercalatively bind to the RNA: DNA hybrid by making an additional intracomplex hydrogen bond. This hydrogen bonding capability of N8 has been confirmed in the crystal structure of the chromophore of N8-actinomycin D. Thus, N8-actinomycin D has been synthesized by coupling the pyridine and benzene fragments obtained independently. A binding study indicates that both actinomycin D and N8-actinomycin D bind intercalatively not only to DNA:DNA double strands but also to RNA:DNA hybrids. Although the overall binding capacity of N8-actinomycin D is reduced substantially in comparison with that of actinomycin D itself, N8-actinomycin D tends to bind relatively more favorably than actinomycin D to the RNA:DNA hybrids. Thus, this initial attempt at designing an RNA:DNA hybrid binding agent appears to be successful. However, it is necessary to modify the agent further to increase its RNA:DNA hybrid binding character and to decrease the DNA:DNA binding character, in order to make a useful RNA:DNA hybrid binding agent.

  DOI：

  10.1021/ja00085a002

文献信息

• Aryl nitrogen-containing bicyclic compounds and methods of use
  申请人：Patel F. Vinod

  公开号：US20070054916A1

  公开（公告）日：2007-03-08

  The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation, cancer and related conditions. The compounds have a general Formula I wherein A 1 , A 2 , A 3 , B, R 1 , R 2 , R 3 and R 4 are defined herein. Accordingly, the invention also comprises pharmaceutical compositions comprising the compounds of the invention, methods for the prophylaxis and treatment of kinase mediated diseases using the compounds and compositions of the invention, and intermediates and processes useful for the preparation of compounds of the invention.

  这项发明涉及一类新的化合物，用于预防和治疗蛋白激酶介导的疾病，包括炎症、癌症和相关疾病。这些化合物具有一般的化学式I，其中A1、A2、A3、B、R1、R2、R3和R4在此有定义。因此，该发明还涉及包括该发明的化合物的药物组合物，使用该发明的化合物和组合物预防和治疗激酶介导的疾病的方法，以及用于制备该发明的化合物的中间体和方法。
• [EN] HETEROARYL SUBSTITUTED INDOLE COMPOUNDS USEFUL AS MMP-13 INHIBITORS<br/>[FR] COMPOSÉS INDOLE À SUBSTITUTION HÉTÉROARYLE UTILISÉS COMME INHIBITEURS DE MMP-13
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2010045188A1

  公开（公告）日：2010-04-22

  Disclosed are compounds and compositions of the formula I as described herein which are inhibitors of MMP-13. Also disclosed are methods of using and making compounds of the formula I.

  披露了公式I的化合物和组合物，如本文所述，它们是MMP-13的抑制剂。还披露了使用和制造公式I化合物的方法。
• HETEROARYL SUBSTITUTED PIPERIDINES
  申请人：Baumann Karlheinz

  公开号：US20110201605A1

  公开（公告）日：2011-08-18

  The invention relates to compounds of formula where hetaryl I, hetaryl II, R 1 , R 2 , R 3 , R 4 , m, n, and o are as defined in the specification or to pharmaceutically active acid addition salts thereof. The compounds of formula I are modulators for amyloid beta and thus may be useful for the treatment or prevention of a disease associated with the deposition of β-amyloid in the brain, in particular Alzheimer's disease, and other diseases such as cerebral amyloid angiopathy, hereditary cerebral hemorrhage with amyloidosis, Dutch-type (HCHWA-D), multi-infarct dementia, dementia pugilistica and Down syndrome.

  该发明涉及以下式的化合物 其中hetaryl I，hetaryl II， R 1 ， R 2 ， R 3 ，R 4 ，m，n和o如规范中所定义 或其药用活性酸盐。式I的化合物是淀粉样蛋白β的调节剂，因此可能对与大脑中β-淀粉样蛋白沉积相关的疾病的治疗或预防有用，特别是阿尔茨海默病，以及其他疾病，如脑淀粉样血管病，遗传性脑出血伴淀粉样变性，荷兰型（HCHWA-D），多梗塞性痴呆，拳击性痴呆和唐氏综合征。
• Preparation of substituted pyridine N-oxide compounds
  申请人：——

  公开号：US20040063957A1

  公开（公告）日：2004-04-01

  A process for preparing substituted pyridine N-oxide compounds of the formula 1 in which R1, R2, R3 and R4 are each H, a carboxyl group or a C 1 -C 12 -alkyl radical which may contain atoms from the group of N, O and S, or R1 and R2 and/or R3 and R4 together may each form an optionally substituted C 4 -C 20 -alkylene radical which may contain atoms from the group of N, O and S, A is benzyl or a (CH 2 ) m group where m may be an integer from 1 to 12, Z 1 and Z 2 are each independently O or S, and Y is H, a C 1 -C 12 -alkyl radical which may optionally contain atoms from the group of N, O and S, a C 6 -C 20 -aryl radical or a C 5 -C 20 -heterocycle, and the radicals may optionally be substituted, or Z 2 and Y together form an optionally substituted ring or ring system, in which case the ring or ring system may contain atoms from the group of N, O and S, from the corresponding 4-halopyridine N-oxide of the formula 2 in which X is chlorine, bromine or iodine, by reacting the compound of the formula (II), in the presence of a phase transfer catalyst and of a base, with a compound of the formula HZ 1 -A-Z 2 -Y  (III) in which Z 1 , Z 2 , A and Y are each as defined above, at a temperature up to the reflux temperature, to give the corresponding substituted pyridine N-oxide compound of the formula (I), and also a process for preparing the compound of the formula (II).

  一种制备取代吡啶N-氧化物化合物的方法，该化合物的公式为1，其中R1、R2、R3和R4分别为H、羧基或可能含有N、O和S的C1-C12烷基基团，或者R1和R2和/或R3和R4可以共同形成一个可选取代的C4-C20烷基基团，该基团可能含有N、O和S的原子，A为苄基或(CH2)m基团，其中m可以是1到12的整数，Z1和Z2各自独立地为O或S，Y为H、C1-C12烷基基团，该基团可以选择地含有N、O和S的原子，C6-C20芳基基团或C5-C20杂环，且基团可以选择性地被取代，或者Z2和Y共同形成一个可选择性取代的环或环系统，此时该环或环系统可以含有N、O和S的原子，从公式2中相应的4-卤代吡啶N-氧化物开始，其中X为氯、溴或碘，通过在相转移催化剂和碱存在下，将公式（II）的化合物与公式HZ1-A-Z2-Y（III）的化合物在回流温度以下的温度下反应，从而得到公式（I）的相应取代吡啶N-氧化物化合物，以及制备公式（II）的化合物的方法。
• Heteroaryl Substituted Indole Compounds Useful as MMP-13 Inhibitors
  申请人：Abeywardane Asitha

  公开号：US20110275631A1

  公开（公告）日：2011-11-10

  Disclosed are compounds and compositions of the formula I as described herein which are inhibitors of MMP-13. Also disclosed are methods of using and making compounds of the formula I.

  本文披露了一种公式I的化合物和组合物，其为MMP-13的抑制剂。同时还披露了使用和制备公式I化合物的方法。