N-[6-(4-氯苯氧基)己基]-N'-氰基-N''-4-吡啶基胍 | 200484-11-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: N-[6-(4-氯苯氧基)己基]-N'-氰基-N''-4-吡啶基胍
• 英文名称: N-cyano-N'-(6-(p-chlorophenoxy)hexyl)-N"-(4-pyridyl)guanidine
• 英文别名: 2-[6-(4-Chlorophenoxy)hexyl]-1-cyano-3-pyridin-4-ylguanidine
• CAS: 200484-11-3
• 化学式: C₁₉H₂₂ClN₅O
• 分子量: 371.87
• InChiKey: BOIPLTNGIAPDBY-UHFFFAOYSA-N

物化性质

• 熔点：
  166-168°C
• 沸点：
  532.1±58.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)
• 溶解度：
  在DMSO中的溶解度为20mg/mL，澄清

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  26
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  82.3
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  -20℃

SDS

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SECTION 1: Identification of the substance/mixture and of the company/undertaking
Product identifiers
Product name : GMX1778
: SML0646
REACH No. : A registration number is not available for this substance as the substance
or its uses are exempted from registration, the annual tonnage does not
require a registration or the registration is envisaged for a later
registration deadline.
CAS-No. : 200484-11-3

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SECTION 2: Hazards identification
Classification of the substance or mixture
Classification according to Regulation (EC) No 1272/2008
Acute toxicity, Oral (Category 4), H302
Skin irritation (Category 2), H315
Eye irritation (Category 2), H319
Specific target organ toxicity - single exposure (Category 3), Respiratory system, H335
For the full text of the H-Statements mentioned in this Section, see Section 16.
Classification according to EU Directives 67/548/EEC or 1999/45/EC
T Toxic R25, R36/37/38
For the full text of the R-phrases mentioned in this Section, see Section 16.
Label elements
Labelling according Regulation (EC) No 1272/2008
Pictogram
Signal word Warning
Hazard statement(s)
Harmful if swallowed.
Causes skin irritation.
Causes serious eye irritation.
May cause respiratory irritation.
Precautionary statement(s)
Avoid breathing dust.
P305 + P351 + P338 IF IN EYES: Rinse cautiously with water for several minutes. Remove
contact lenses, if present and easy to do. Continue rinsing.
Supplemental Hazard none
Statements
Other hazards - none

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SECTION 3: Composition/information on ingredients
Substances
Synonyms : CHS-828
N-[6-4-Chlorophenoxy)hexyl]-N'-cyano-?N''-4-pyridinyl-guanidine
Formula : C19H22ClN5O
Molecular Weight : 371,86 g/mol
CAS-No. : 200484-11-3
Hazardous ingredients according to Regulation (EC) No 1272/2008
Component Classification Concentration
N-[6-4-Chlorophenoxy)hexyl]-N'-cyano-?N''-4-pyridinyl-guanidine
Acute Tox. 4; Skin Irrit. 2; Eye -
Irrit. 2; STOT SE 3; H302,
H315, H319, H335
Hazardous ingredients according to Directive 1999/45/EC
Component Classification Concentration
N-[6-4-Chlorophenoxy)hexyl]-N'-cyano-?N''-4-pyridinyl-guanidine
T, R25 - R36/37/38 -
For the full text of the H-Statements and R-Phrases mentioned in this Section, see Section 16

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SECTION 4: First aid measures
Description of first aid measures
General advice
Consult a physician. Show this safety data sheet to the doctor in attendance.
If inhaled
If breathed in, move person into fresh air. If not breathing, give artificial respiration. Consult a physician.
In case of skin contact
Wash off with soap and plenty of water. Consult a physician.
In case of eye contact
Rinse thoroughly with plenty of water for at least 15 minutes and consult a physician.
If swallowed
Never give anything by mouth to an unconscious person. Rinse mouth with water. Consult a physician.
Most important symptoms and effects, both acute and delayed
The most important known symptoms and effects are described in the labelling (see section 2.2) and/or in
section 11
Indication of any immediate medical attention and special treatment needed
no data available

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SECTION 5: Firefighting measures
Extinguishing media
Suitable extinguishing media
Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Special hazards arising from the substance or mixture
Carbon oxides, nitrogen oxides (NOx), Hydrogen chloride gas
Advice for firefighters
Wear self contained breathing apparatus for fire fighting if necessary.
Further information
no data available

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SECTION 6: Accidental release measures
Personal precautions, protective equipment and emergency procedures
Use personal protective equipment. Avoid dust formation. Avoid breathing vapours, mist or gas. Ensure
adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust.
For personal protection see section 8.
Environmental precautions
Do not let product enter drains.
Methods and materials for containment and cleaning up
Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed
containers for disposal.
Reference to other sections
For disposal see section 13.

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SECTION 7: Handling and storage
Precautions for safe handling
Avoid contact with skin and eyes. Avoid formation of dust and aerosols.
Provide appropriate exhaust ventilation at places where dust is formed.
For precautions see section 2.2.
Conditions for safe storage, including any incompatibilities
Store in cool place. Keep container tightly closed in a dry and well-ventilated place.
Recommended storage temperature: -20 °C
Specific end use(s)
A part from the uses mentioned in section 1.2 no other specific uses are stipulated

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SECTION 8: Exposure controls/personal protection
Control parameters
Components with workplace control parameters
Exposure controls
Appropriate engineering controls
Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and
at the end of workday.
Personal protective equipment
Eye/face protection
Safety glasses with side-shields conforming to EN166 Use equipment for eye protection tested
and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).
Skin protection
Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique
(without touching glove's outer surface) to avoid skin contact with this product. Dispose of
contaminated gloves after use in accordance with applicable laws and good laboratory practices.
Wash and dry hands.
The selected protective gloves have to satisfy the specifications of EU Directive 89/686/EEC and
the standard EN 374 derived from it.
Body Protection
Complete suit protecting against chemicals, The type of protective equipment must be selected
according to the concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection
For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator.For higher
level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges.
Use respirators and components tested and approved under appropriate government standards
such as NIOSH (US) or CEN (EU).
Control of environmental exposure
Do not let product enter drains.

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SECTION 9: Physical and chemical properties
Information on basic physical and chemical properties
a) Appearance Form: solid
b) Odour no data available
c) Odour Threshold no data available
d) pH no data available
e) Melting point/freezing no data available
point
f) Initial boiling point and no data available
boiling range
g) Flash point no data available
h) Evapouration rate no data available
i) Flammability (solid, gas) no data available
j) Upper/lower no data available
flammability or
explosive limits
k) Vapour pressure no data available
l) Vapour density no data available
m) Relative density no data available
n) Water solubility no data available
o) Partition coefficient: n- log Pow: 3,902
octanol/water
p) Auto-ignition no data available
temperature
q) Decomposition no data available
temperature
r) Viscosity no data available
s) Explosive properties no data available
t) Oxidizing properties no data available
Other safety information
no data available

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SECTION 10: Stability and reactivity
Reactivity
no data available
Chemical stability
Stable under recommended storage conditions.
Possibility of hazardous reactions
no data available
Conditions to avoid
no data available
Incompatible materials
Strong oxidizing agents
Hazardous decomposition products
Other decomposition products - no data available
In the event of fire: see section 5

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SECTION 11: Toxicological information
Information on toxicological effects
Acute toxicity
no data available
Skin corrosion/irritation
no data available
Serious eye damage/eye irritation
no data available
Respiratory or skin sensitisation
no data available
Germ cell mutagenicity
no data available
Carcinogenicity
IARC: No component of this product present at levels greater than or equal to 0.1% is identified as
probable, possible or confirmed human carcinogen by IARC.
Reproductive toxicity
no data available
Specific target organ toxicity - single exposure
Inhalation - May cause respiratory irritation.
Specific target organ toxicity - repeated exposure
no data available
Aspiration hazard
no data available
Additional Information
RTECS: Not available
To the best of our knowledge, the chemical, physical, and toxicological properties have not been
thoroughly investigated.

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SECTION 12: Ecological information
Toxicity
no data available
Persistence and degradability
no data available
Bioaccumulative potential
no data available
Mobility in soil
no data available
Results of PBT and vPvB assessment
PBT/vPvB assessment not available as chemical safety assessment not required/not conducted
Other adverse effects
no data available

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SECTION 13: Disposal considerations
Waste treatment methods
Product
Offer surplus and non-recyclable solutions to a licensed disposal company. Dissolve or mix the material
with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber.
Contaminated packaging
Dispose of as unused product.

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SECTION 14: Transport information
UN number
ADR/RID: 2811 IMDG: 2811 IATA: 2811
UN proper shipping name
ADR/RID: TOXIC SOLID, ORGANIC, N.O.S. (N-[6-4-Chlorophenoxy)hexyl]-N'-cyano-?N''-4-pyridinyl-
guanidine)
IMDG: TOXIC SOLID, ORGANIC, N.O.S. (N-[6-4-Chlorophenoxy)hexyl]-N'-cyano-?N''-4-pyridinyl-
guanidine)
IATA: Toxic solid, organic, n.o.s. (N-[6-4-Chlorophenoxy)hexyl]-N'-cyano-?N''-4-pyridinyl-guanidine)
Transport hazard class(es)
ADR/RID: 6.1 IMDG: 6.1 IATA: 6.1
Packaging group
ADR/RID: III IMDG: III IATA: III
Environmental hazards
ADR/RID: no IMDG Marine pollutant: no IATA: no
Special precautions for user
no data available

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SECTION 15: Regulatory information
This safety datasheet complies with the requirements of Regulation (EC) No. 1907/2006.
Safety, health and environmental regulations/legislation specific for the substance or mixture
no data available
Chemical Safety Assessment
Causes serious eye irritation.
May cause respiratory irritation.
Skin Irrit. Skin irritation
Full text of R-phrases referred to under sections 2 and 3
T Toxic
R25 Toxic if swallowed.
R36/37/38 Irritating to eyes, respiratory system and skin.
Further information
only.
The above information is believed to be correct but does not purport to be all inclusive and shall be
used only as a guide. The information in this document is based on the present state of our knowledge
and is applicable to the product with regard to appropriate safety precautions. It does not represent any

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

生物活性

GMX1778 (CHS828) 是一种有效的特异性烟酰胺磷酸核糖转移酶（NAMPT）抑制剂，其IC50和Kd分别为<25 nM 和120 nM。GMX1778 可诱导具有凋亡特征的细胞程序性死亡，并进入Phase 1阶段。

靶点

Target	Value
NAMPT	<25 nM
NAMPT (Kd)	120 nM

体外研究

GMX1778通过抑制NAD+生物合成诱导NAD+消耗，进而导致ATP耗竭，最终使细胞死亡。此外，GMX1778还诱导了程序性细胞死亡，并伴随凋亡特征。进一步的研究显示，GMX1778能下调IKK活性，从而在癌症细胞中抑制核因子κB（IC50=8 nM）。

体内研究

在移植的裸鼠模型中，GMX1778 (250 mg/kg, p.o.)对三种不同类型的人神经内分泌肿瘤、肠癌(GOT1)、胰腺癌(BON)，以及甲状腺髓样癌(GOT2)表现出显著的抗肿瘤活性。

反应信息

• 作为反应物：
  描述：

  N-[6-(4-氯苯氧基)己基]-N'-氰基-N''-4-吡啶基胍 在 N-溴代丁二酰亚胺(NBS) 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以66%的产率得到N-[6-(4-chlorophenoxy)hexyl]-N'-cyano-N''-4-(3,5-dibromopyridyl)-guanidine
  参考文献：
  名称：

  氚标记的 CHS 828 及其前药 EB 1627 的合成

  摘要：

  有效的抗肿瘤氰基胍 CHS 828 及其前药 EB 1627 已成功用氚标记。CHS 828 的吡啶基-3,5-二溴衍生物用 Pd/C 催化剂用氚气脱溴得到 [pyridyl-3,5-3H2]-CHS 828，放射化学纯度为 99.3%，比活度为 1960 GBq/毫摩尔。类似地，前药 EB 1627 的 pyridyl-3-bromo 衍生物用氚气脱溴得到 [pyridyl-3-3H]-EB 1627，放射化学纯度为 98.1%，比活度为 894 GBq/mmol。版权所有 © 2005 John Wiley & Sons, Ltd.

  DOI：

  10.1002/jlcr.997
• 作为产物：
  描述：

  4-氨基吡啶 在 吡啶 、 4-二甲氨基吡啶 、 sodium hydride 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 paraffin 为溶剂， 反应 11.0h， 生成 N-[6-(4-氯苯氧基)己基]-N'-氰基-N''-4-吡啶基胍
  参考文献：
  名称：

  Novel cyanoguanidines with potent oral antitumour activity

  摘要：

  4-Pyridyl cyanoguanidines with hydrophobic aromatic side chains showed potent antiproliferative activity in the human breast and lung cancer cell lines MCF-7, NYH and H460. In vivo, treatment with N-(6-chlorophenoxyhexyl)-N'-cyano-N "-4-pyridylguanidine (18, 20 mg/kg/day po.), gave a complete remission of tumours in a model of NYH inoculated nude mice. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)10152-4
• 作为试剂：
  描述：

  N-[6-(4-氯苯氧基)己基]-N'-氰基-N''-4-吡啶基胍 、 iodomethyl 2-(2-(2-(2-methoxy-ethoxy)-ethoxy)-ethoxy)-ethyl carbonate 在 N-[6-(4-氯苯氧基)己基]-N'-氰基-N''-4-吡啶基胍 作用下， 生成
  参考文献：
  名称：

  Cyanoguanidine prodrugs

  摘要：

  本发明揭示了一种适用于治疗用途的化合物，其化学式如下。本发明还揭示了包含该化合物的组合物，涉及将该化合物用于患者治疗的治疗方法，以及将该化合物用于制造药物的用途。

  公开号：

  US06525077B2

文献信息

• [EN] CYANOGUANIDINE PRODRUGS<br/>[FR] PROMEDICAMENTS DE CYANOGUANIDINE
  申请人：LEO PHARMA AS

  公开号：WO2003097601A1

  公开（公告）日：2003-11-27

  Pyridyl cyanoguanidine compounds of the general formula I wherein A, X1, X2, X3, Y1, Y2, Y3, R1, R2, R5, R6 and n are as indicated in the description are suitable as prodrugs in human and veterinary therapy of proliferative diseases such as cancers.

  通用式I中的吡啶基氰胍化合物，其中A、X1、X2、X3、Y1、Y2、Y3、R1、R2、R5、R6和n如描述中所示，适用于作为前药在人类和兽医治疗增殖性疾病如癌症中使用。
• [EN] CYANOGUANIDINE PRODUGS<br/>[FR] PROMEDICAMENTS CONSTITUES DE CYANOGUANIDINE
  申请人：LEO PHARMA AS

  公开号：WO2003097602A1

  公开（公告）日：2003-11-27

  Pyridyl cyanoguanidine compounds according to formula I wherein A, R1, R2, R5, R6, X1, X2, X3, X4, Y1, Y2, Y3, Y4 and n are as indicated in the description are useful as produgs in human and veterinary therapy of poliferative disease such as cancers.

  根据描述中所示的公式I，吡啶基氰胍胺化合物在人类和兽医治疗癌症等增殖性疾病中作为前药是有用的。
• PYRIDYL CYANOGUANIDINE DERIVATIVES
  申请人：Zhang Hesheng

  公开号：US20120309797A1

  公开（公告）日：2012-12-06

  Compounds of formula (I) or pharmaceutically acceptable salts thereof, and use for treating cancer thereof are disclosed, wherein, the definitions of X, Y, R 1 , R 2 and n are described in description.

  公式（I）的化合物或其药用盐的使用，以及用于治疗癌症的方法已被披露，其中，X、Y、R1、R2和n的定义在描述中描述。
• Novel pyridyl cyanoguanidine compounds
  申请人：——

  公开号：US20040220408A1

  公开（公告）日：2004-11-04

  Compounds according to formula (I) 1 wherein R1 represents hydrogen, halogen or one or more straight or branched, saturated or unsaturated C 1-6 hydrocarbon radical, optionally substituted with halogen, hydroxy, cyano, nitro, carboxy, alkoxy, alkoxycarbonyl, alkylcarbonyl, formyl, amico, aminoalkyl, aminocarbonyl, alkylcarbonylamino, sulfo, aminosulfonyl, alkylsulfonylamino, hydroxysulfonyloxy, dihydroxyphosphinoyloxy or phosphono; X represents a straight or branched, saturated or unsaturated C 1-12 hydrocarbon diradical, optionaly substituted with halogen, hydroxy, cyano, nitro, carboxy, alkoxy, alkoxycarbonyl, alkylcarbonyl, formyl, amino, aminoalkyl, aminocarbonyl, alkylcarbonylamino, sulfo, aminosulfonyl, alkylsulfonylamino, hydroxysulfonyloxy, dihydroxyphosphinoyloxy or phosphono; Y represents a bond, O, C(O), S, S(O), S(O) 2 , C(O)O, NH, C(O)NH, OC(O) or NHC(O); Z represents an aromatic or non-aromatic heterocyclic radical with 5-12 ring atoms, optionally substituted with halogen, hydroxy, cyano, nitro, alkoxy, alkoxycarbonyl, alkylcarbonyl, formyl, aminoalkyl or straight or branched, saturated or unsaturated C 1-4 hydrocarbon radical, optionally substituted with halogen, hydroxy, cyano, nitro, alkoxy, alkoxycarbonyl, alkylcarbonyl, formyl or aminoalkyl; provided that R1 is not attached to the nitrogen-atom in the pyridyl ring, and pharmaceutically acceptable salts, solvates, hydrates, N-oxides and prodrugs thereof are disclosed. The compounds are useful in therapy.

  根据式（I）1，其中R1代表氢，卤素或一个或多个直链或支链、饱和或不饱和的C1-6烃基，可选地用卤素、羟基、氰基、硝基、羧基、烷氧基、烷氧羰基、烷基羰基、甲酰基、酰胺基、氨基烷基、氨基羰基、烷基酰胺基、磺酸基、氨基磺酰基、烷基磺酰胺基、羟基磺酰氧基、二羟基膦酰氧基或磷酸基取代；X代表直链或支链、饱和或不饱和的C1-12双基，可选地用卤素、羟基、氰基、硝基、羧基、烷氧基、烷氧羰基、烷基羰基、甲酰基、氨基、氨基烷基、氨基羰基、烷基酰胺基、磺酸基、氨基磺酰基、烷基磺酰胺基、羟基磺酰氧基、二羟基膦酰氧基或磷酸基取代；Y代表键、O、C（O）、S、S（O）、S（O）2、C（O）O、NH、C（O）NH、OC（O）或NHC（O）；Z代表具有5-12个环原子的芳香或非芳香杂环基，可选地用卤素、羟基、氰基、硝基、烷氧基、烷氧羰基、烷基羰基、甲酰基、氨基烷基或直链或支链、饱和或不饱和的C1-4烃基，可选地用卤素、羟基、氰基、硝基、烷氧基、烷氧羰基、烷基羰基、甲酰基或氨基烷基取代；但要求R1不连接到吡啶环中的氮原子，并且公开了其药学上可接受的盐、溶剂化合物、水合物、N-氧化物和前药。这些化合物在治疗中有用。
• Novel Cyanoguanidine Compounds
  申请人：Bjørkling Fredrik

  公开号：US20080312275A1

  公开（公告）日：2008-12-18

  Novel pyridyl cyanoguanidine compounds of general formula I (I) wherein R 1 , X, R 2 and R 3 are as defined herein, exhibit a high antiproliferative activity and may be used in the treatment of hyperproliferative and neo-plastic diseases.

  通式为I（I）的新型吡啶基氰脲化合物，其中R1、X、R2和R3的定义如本文所述，具有较高的抗增殖活性，可用于治疗过度增殖和新生质性疾病。