1-甲基-1,2,3,4-四氢-1,5-萘啶 | 381227-91-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 1-甲基-1,2,3,4-四氢-1,5-萘啶
• 英文名称: 1-Methyl-1,2,3,4-tetrahydro-1,5-naphthyridine
• 英文别名: 1-methyl-3,4-dihydro-2H-1,5-naphthyridine
• CAS: 381227-91-4
• 化学式: C₉H₁₂N₂
• 分子量: 148.208
• InChiKey: NATRVVUJQGDXNM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  16.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-甲基-1,2,3,4-四氢-1,5-萘啶 在 Rh/Al₂O₃ 氢气 作用下， 20.0 ℃ 、6.89 MPa 条件下， 以62%的产率得到1-methyl-decahydro-[1,5]naphthyridine
  参考文献：
  名称：

  Synthesis and conformational properties of N-monoalkyl 1,5-diaza-cis-decalins

  摘要：

  N-Monoalkyl 1,5-diaza-cis-decalins were synthesized in high yield and purity by derivatization of tetrahydronaphthyridine followed by reduction to the saturated system. The position of the conformational equilibrium between the chair-chair inversion forms of a series of four N-monoalkyl of 1,5-diaza-cis-decalins was measured and was directly related to the size of the N-alkyl group. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(01)01344-2
• 作为产物：
  描述：

  1,5-萘啶 在 Rh/Al₂O₃ 甲酸 、 氢气 作用下， 20.0 ℃ 、101.33 kPa 条件下， 生成 1-甲基-1,2,3,4-四氢-1,5-萘啶
  参考文献：
  名称：

  Synthesis and conformational properties of N-monoalkyl 1,5-diaza-cis-decalins

  摘要：

  N-Monoalkyl 1,5-diaza-cis-decalins were synthesized in high yield and purity by derivatization of tetrahydronaphthyridine followed by reduction to the saturated system. The position of the conformational equilibrium between the chair-chair inversion forms of a series of four N-monoalkyl of 1,5-diaza-cis-decalins was measured and was directly related to the size of the N-alkyl group. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(01)01344-2

文献信息

• [EN] NOVEL HETEROCYCLIC DERIVATIVES USEFUL AS SHP2 INHIBITORS<br/>[FR] NOUVEAUX DÉRIVÉS HÉTÉROCYCLIQUES UTILES EN TANT QU'INHIBITEURS DE SHP2
  申请人：JACOBIO PHARMACEUTICALS CO LTD

  公开号：WO2020063760A1

  公开（公告）日：2020-04-02

  Provided is a compound of formula I, their synthesis and their use for treating a SHP2 mediated disorder. More particularly, provided is a pharmaceutical composition comprising the said compound.

  提供的是一种化合物I的配方，它们的合成以及它们用于治疗SHP2介导的疾病。更具体地，提供的是包含该化合物的药物组合物。
• [EN] 3-SUBSTITUTED CARBONYL-NAPHTHO[2,3-B]FURANE DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF<br/>[FR] DÉRIVÉ DE CARBONYLE -NAPHTO [2,3-B]FURANE 3-SUBSTITUÉ DÉRIVÉ OU SEL PHARMACEUTIQUEMENT ACCEPTABLE DE CELUI-CI
  申请人：BOSTON BIOMEDICAL INC

  公开号：WO2015120304A1

  公开（公告）日：2015-08-13

  The present invention provides a compound of the following Formula (1) or a pharmaceutically acceptable salt thereof: Formule (i) wherein X is an oxygen atom and the like; Y is -CO-, -S02-and the like; R1 is an optionally- substituted C1-6 alkyl group, an optionally-substituted C1-6 alkylcarbonyl group and the like; R2 is an optionally- substituted C1-6 alkyl group, an optionally-substituted C1-6 alkoxy group, an optionally-substituted amino group, an optionally-substituted 5- to 12-membered monocyclic or polycyclic saturated heterocyclic group and the like; R3, R4, R5, and R6 are independently a hydrogen atom and the like which exhibits excellent effects in suppressing the proliferation and sphere-forming ability of cancer cells, and can be useful as an antitumor drug or cell growth inhibitor.

  本发明提供以下式（1）的化合物或其药学上可接受的盐：式（i）其中X是氧原子等；Y是-CO-，-S02-等；R1是可选择地取代的C1-6烷基，可选择地取代的C1-6烷基羰基等；R2是可选择地取代的C1-6烷基，可选择地取代的C1-6烷氧基，可选择地取代的氨基，可选择地取代的5-至12-成员的单环或多环饱和杂环基等；R3、R4、R5和R6独立地是氢原子等，对抑制癌细胞的增殖和球形形成能力具有出色效果，并可用作抗肿瘤药物或细胞生长抑制剂。
• FUSED HETEROCYCLIC COMPOUND
  申请人：Ishikawa Tomoyasu

  公开号：US20100216788A1

  公开（公告）日：2010-08-26

  The present invention provides a compound represented by the formula: wherein R 1a is a hydrogen atom, R 2a is a C 1-6 alkyl group substituted by a group represented by —NR 6a —CO—(CH 2 ) n —SO 2 — optionally halogenated C 1-4 alkyl wherein n is an integer of 1 to 4, R 6a is a hydrogen atom or a C 1-4 alkyl group, and —(CH 2 ) n — is optionally substituted by C 1-4 alkyl, R 3a is a hydrogen atom or a C 1-6 alkyl group, R 4a is a halogen atom or a C 1-6 alkyl group, R 5a is a halogen atom or a C 1-6 alkyl group, and X a is a hydrogen atom or a halogen atom, or a salt thereof. The compound of the present invention has a superior tyrosine kinase inhibitory action, is highly safe, and is sufficiently satisfactory as a pharmaceutical product.

  本发明提供了一种化合物，其表示为以下式子：其中，R1a是氢原子，R2a是一个C1-6烷基，被一个表示为—NR6a—CO—（CH2）n—SO2—的基团取代，该基团可选地卤代C1-4烷基，其中n是1至4的整数，R6a是氢原子或C1-4烷基，—（CH2）n—可选地被C1-4烷基取代，R3a是氢原子或C1-6烷基，R4a是卤原子或C1-6烷基，R5a是卤原子或C1-6烷基，Xa是氢原子或卤原子，或其盐。本发明的化合物具有卓越的酪氨酸激酶抑制作用，高度安全，并且作为药物产品完全令人满意。
• FUSED NITROGEN-COMPRISING HETEROCYCLIC COMPOUND
  申请人：Seto Masaki

  公开号：US20100234351A1

  公开（公告）日：2010-09-16

  A compound of the formula: wherein ring A is a 7-membered or 8-membered nitrogen-containing ring optionally further substituted, ring B is an optionally substituted aryl group or an optionally substituted heteroaryl group, X 1 is a group represented by —NR 3 —Y 1 —, —O—, —S—, —SO—, —SO 2 — or —CHR 3 — wherein R 3 is a hydrogen atom or an optionally substituted aliphatic hydrocarbon group, or R 3 may be bonded to the carbon atom of ring B to form an optionally substituted ring structure, and Y 1 is a bond or an optionally substituted alkylene, R 1 is a hydrogen atom, or an optionally substituted group bonded via a carbon atom or a sulfur atom, the formula shows a single bond or a double bond, when R 2 is —R 2 , R 2 is a hydrogen atom, or an optionally substituted group bonded via a carbon atom, a nitrogen atom, an oxygen atom or a sulfur atom, and when R 2 is ═R 2 , R 2 is an oxo group, an optionally substituted alkylidene group, or an optionally substituted imino group.

  该化合物的化学式为：其中环A是一个7-或8-成员的含氮环，可选择进一步取代，环B是一个可选择取代的芳基或杂芳基，X1是一个由—NR3—Y1—、—O—、—S—、—SO—、—SO2—或—CHR3—表示的基团，其中R3是氢原子或可选择取代的脂肪烃基团，或R3可与环B的碳原子结合形成可选择取代的环结构，Y1是一个键或可选择取代的烷基，R1是氢原子或通过碳原子或硫原子结合的可选择取代的基团，化学式中显示单键或双键，当R2是—R2时，R2是氢原子或通过碳原子结合的可选择取代的基团，氮原子、氧原子或硫原子，当R2是═R2时，R2是一个氧代基团、可选择取代的烷基亚甲基基团或可选择取代的亚胺基团。
• Heteroaryl sulfonamides and CCR2
  申请人：ChemoCentryx, Inc.

  公开号：EP2474532A1

  公开（公告）日：2012-07-11

  A compound of the formula (I), or a salt thereof: where Ar is selected from the group consisting of substituted or unsubstituted C6-10 aryl and substituted or unsubstituted 5- to 10-membered heteroaryl; R1 is selected from the group consisting of hydrogen, unsubstituted C1 alkyl, substituted or unsubstituted C3-8 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, and substituted or unsubstituted 3- to 10-membered heterocyclyl; Y1 is selected from the group consisting of -CR2a-, -N-, and -N+(O)--; Y2 is selected from the group consisting of -CR2b-, -N-, and -N+(O)--; Y3 is selected from the group consisting of -CR2c-, -N-, and -N+(O)--; R2a, R2b, and R2c are each independently selected from the group consisting of hydrogen, halogen, -CN, -C(O)R3, -CO2R3, -C(O)NR3R4, -OR3, - OC(O)R3, -OC(O)NR3R4, -SR3, -S(O)R3, -S(O)2R3, -S(O)2NR3R4, -NO2, -NR3R4, -NR3C(O)R4, -NR3C(O)OR4, -NR3S(O)2R4, -NR3C(O)NR4R5, substituted or unsubstituted C1-8 alkyl, substituted or unsubstituted C2-8 alkenyl, substituted or unsubstituted C2-8 alkynyl, substituted or unsubstituted 3- to 10-membered heterocyclyl, substituted or unsubstituted C6-10 aryl, and substituted or unsubstituted 5- to 10-membered heteroaryl; R3, R4, and R5 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted C1-8 alkyl, substituted or unsubstituted C2-8 alkenyl, substituted or unsubstituted C2-8 alkynyl, substituted or unsubstituted C6-10 aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, and substituted or unsubstituted 3- to 10-membered heterocyclyl; R3 and R4, R4 and R5 or R3 and R5 may, together with the atoms to which they are attached, form a substituted or unsubstituted 5-, 6-, or 7-membered ring; Y4 is selected from the group consisting of -N- and -N+(O)--; L is selected from the group consisting of a bond, -O-, -S-, -S(O)-, S(O)2-, - CR6R7-, -NR8-, -C(O)- and -NR8C(O)-; R6 and R7 are each independently selected from the group consisting of hydrogen, halogen, substituted or unsubstituted C1-8 alkyl, substituted or unsubstituted 3- to 10-membered heterocyclyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, -CN, -OR9, -NR10R11, -S(O)R9, and -S(O)2R9; R6 and R7 may, together with the carbon atom to which they are attached, form substituted or unsubstituted C3-8 cycloalkyl or substituted or unsubstituted 3-to 10-membered heterocyclic ring; R9 is selected from the group consisting of hydrogen, substituted or unsubstituted C1-8 alkyl, substituted or unsubstituted C2-8 alkenyl, substituted or unsubstituted C2-8 alkynyl, substituted or unsubstituted C6-10 aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, and substituted or unsubstituted 3- to 10-membered heterocyclyl; R10 and R11 are each independently selected from the group consisting of substituted or unsubstituted C1-8 alkyl, substituted or unsubstituted 3- to 10-membered heterocyclyl, substituted or unsubstituted C6-10 aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, substituted or unsubstituted C2-8 alkenyl, and substituted or unsubstituted C2-8 alkynyl; R10 and R11 of -NR10R11 may, together with the nitrogen, form a substituted or unsubstituted C3-8 cycloalkyl or substituted or unsubstituted 3- to 10-membered heterocyclyl; R8 is selected from the group consisting of hydrogen, C(O)R12, S(O)2R12, CO2R12, substituted or unsubstituted C1-8 alkyl, substituted or unsubstituted 3- to 10-membered heterocyclyl, substituted or unsubstituted C2-6 alkenyl, and substituted or unsubstituted C2-6 alkynyl; R12 is selected from the group consisting of substituted or unsubstituted C1-8 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted 3- to 10-membered heterocyclyl, substituted or unsubstituted C6-10 aryl, and substituted or unsubstituted 5- to 10-membered heteroaryl; Z1 is selected from the group consisting of substituted or unsubstituted C6-10 aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, substituted or unsubstituted 3- to 10-membered heterocyclyl, and -NR13R14; R13 and R14 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted C1-8 alkyl, substituted or unsubstituted C2-8 alkenyl, substituted or unsubstituted C2-8 alkynyl, substituted or unsubstituted 3- to 10-membered heterocyclyl, substituted or unsubstituted C6-10 aryl, substituted or unsubstituted 5- to 10-membered heteroaryl, substituted or unsubstituted (C1-4 alkyl)-(C6-10 aryl), and substituted or unsubstituted (C1-4 alkyl)-(5- to 10-membered heteroaryl); R13 and R14 may, together with the nitrogen, form a substituted or unsubstituted 4-, 5-, 6-, or 7-membered heterocyclyl with the proviso that compounds of formula CC are excluded: where X14 is selected from the group consisting of -Cl, -NO2, -OCH3, -CH3, - NHC(O)CH3, and -CH2CH2-(phenyl); R65 is selected from the group consisting of hydrogen, substituted or unsubstituted C1-4 alkyl, and substituted or unsubstituted -SO2(phenyl); and R60 is selected from the group consisting of -NR61CH2CH2OR62, - NR61CH2CH2NR63R64, -NR61CH2CH2SR62, where R61 is selected from the group consisting of hydrogen and substituted or unsubstituted phenyl; R62 is selected from the group consisting of substituted or unsubstituted phenyl, and substituted or unsubstituted C1-4 alkyl; and R63 and R64 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted C1-8 alkyl, substituted or unsubstituted phenyl, substituted or unsubstituted -SO2(phenyl), - C(O)CH3, -C(O)C(O)OH, and -C(O)2C(CH3)3.

  一种具有式(I)或其盐的化合物：其中，Ar选自被取代或未取代的C6-10芳基或被取代或未取代的5-至10元杂芳基；R1选自氢、未取代的C1烷基、被取代或未取代的C3-8烷基、被取代或未取代的C2-6烯基、被取代或未取代的C2-6炔基和被取代或未取代的3-至10元杂环基；Y1选自-CR2a-、-N-和-N+(O)-；Y2选自-CR2b-、-N-和-N+(O)-；Y3选自-CR2c-、-N-和-N+(O)-；R2a、R2b和R2c各自独立地选自氢、卤素、-CN、-C(O)R3、-CO2R3、-C(O)NR3R4、-OR3、-OC(O)R3、-OC(O)NR3R4、-SR3、-S(O)R3、-S(O)2R3、-S(O)2NR3R4、-NO2、-NR3R4、-NR3C(O)R4、-NR3C(O)OR4、-NR3S(O)2R4、-NR3C(O)NR4R5、被取代或未取代的C1-8烷基、被取代或未取代的C2-8烯基、被取代或未取代的C2-8炔基、被取代或未取代的3-至10元杂环基、被取代或未取代的C6-10芳基和被取代或未取代的5-至10元杂芳基；R3、R4和R5各自独立地选自氢、被取代或未取代的C1-8烷基、被取代或未取代的C2-8烯基、被取代或未取代的C2-8炔基、被取代或未取代的C6-10芳基、被取代或未取代的5-至10元杂芳基和被取代或未取代的3-至10元杂环基；R3和R4、R4和R5或R3和R5可与它们所连接的原子一起形成被取代或未取代的5-、6-或7元环；Y4选自-N-和-N+(O)-；L选自键、-O-、-S-、-S(O)-、S(O)2-、-CR6R7-、-NR8-、-C(O)-和-NR8C(O)-；R6和R7各自独立地选自氢、卤素、被取代或未取代的C1-8烷基、被取代或未取代的3-至10元杂环基、被取代或未取代的C2-6烯基、被取代或未取代的C2-6炔基、-CN、-OR9、-NR10R11、-S(O)R9和-S(O)2R9；R6和R7可与它们所连接的碳原子一起形成被取代或未取代的C3-8环烷基或被取代或未取代的3-至10元杂环基；R9选自氢、被取代或未取代的C1-8烷基、被取代或未取代的C2-8烯基、被取代或未取代的C2-8炔基、被取代或未取代的C6-10芳基、被取代或未取代的5-至10元杂芳基和被取代或未取代的3-至10元杂环基；R10和R11各自独立地选自被取代或未取代的C1-8烷基、被取代或未取代的3-至10元杂环基、被取代或未取代的C6-10芳基、被取代或未取代的5-至10元杂芳基、被取代或未取代的C2-8烯基和被取代或未取代的C2-8炔基；-NR10R11中的R10和R11可与氮一起形成被取代或未取代的C3-8环烷基或被取代或未取代的3-至10元杂环基；R8选自氢、C(O)R12、S(O)2R12、CO2R12、被取代或未取代的C1-8烷基、被取代或未取代的3-至10元杂环基、被取代或未取代的C2-6烯基和被取代或未取代的C2-6炔基；R12选自被取代或未取代的C1-8烷基、被取代或未取代的C2-6烯基、被取代或未取代的C2-6炔基、被取代或未取代的3-至10元杂环基、被取代或未取代的C6-10芳基和被取代或未取代的5-至10元杂芳基；Z1选自被取代或未取代的C6-10芳基、被取代或未取代的5-至10元杂芳基、被取代或未取代的3-至10元杂环基和-NR13R14；R13和R14各自独立地选自氢、被取代或未取代的C1-8烷基、被取代或未取代的C2-8烯基、被取代或未取代的C2-8炔基、被取代或未取代的3-至10元杂环基、被取代或未取代的C6-10芳基、被取代或未取代的5-至10元杂芳基、被取代或未取代的(C1-4烷基)-(C6-10芳基)和被取代或未取代的(C1-4烷基)-(5-至10元杂芳基)；R13和R14可与氮一起形成被取代或未取代的4-、5-、6-或7元杂环基；其中排除式CC的化合物：其中，X14选自-Cl、-NO2、-OCH3、-CH3、-NHC(O)CH3和-CH2CH2-(苯基)；R65选自氢、被取代或未取代的C1-4烷基和被取代或未取代的-SO2(苯基)；R60选自-NR61CH2CH2OR62、-NR61CH2CH2NR63R64和-NR61CH2CH2SR62；其中，R61选自氢和被取代或未取代的苯基；R62选自被取代或未取代的苯基和被取代或未取代的C1-4烷基；R63和R64各自独立地选自氢、被取代或未取代的C1-8烷基、被取代或未取代的苯基、被取代或未取代的-SO2(苯基)、-C(O)CH3、-C(O)C(O)OH和-C(O)2C(CH3)3。