妥拉磺脲 | 1156-19-0

• 物质功能分类: 原料药 - 激素及调节内分泌功能类药 - 胰腺激素及其它调节血糖药
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 妥拉磺脲
• 中文别名: 甲磺氮草脲；甲磺氮卓脲；甲磺吖庚脲；庚啶甲苯磺脲；对甲苯磺酰六氮卓脲
• 英文名称: tolazamide
• 英文别名: N-[(azepan-1-ylamino)carbonyl]-4-methylbenzenesulfonamide；1-(azepan-1-yl)-3-(4-methylphenyl)sulfonylurea；ZINC00057512；SJ000285887；N-azepan-1-ylcarbamoyl-toluene-4-sulfonamide
• CAS: 1156-19-0
• 化学式: C₁₄H₂₁N₃O₃S
• mdl: MFCD00083504
• 分子量: 311.405
• InChiKey: OUDSBRTVNLOZBN-UHFFFAOYSA-N

物化性质

• 熔点：
  162-164°C
• 沸点：
  300°C (rough estimate)
• 密度：
  1.2228 (rough estimate)
• 溶解度：
  极微溶于水；易溶于氯仿；溶于丙酮；微溶于乙醇（96%）。
• 物理描述：
  Tolazamide appears as white to off-white crystalline powder. Odorless or with a slight odor. (NTP, 1992)
• 颜色/状态：
  Crystals
• 气味：
  ODORLESS OR HAS SLIGHT ODOR
• 水溶性：
  -3.68
• 解离常数：
  PKA @ 25 °C, 3.6; PKA @ 37.5 °C, 5.68
• 碰撞截面：
  173.3 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  86.9
• 氢给体数：
  2
• 氢受体数：
  4

ADMET

代谢

妥拉唑胺代谢成五种主要代谢物，其降糖活性从0到70%不等。

Tolazamide is metabolized to five major metabolites ranging in hypoglycemic activity from 0 to 70%.

来源:DrugBank

代谢

甲苯磺丁脲代谢成多种降血糖物质...

TOLAZAMIDE IS METABOLIZED TO A NUMBER OF HYPOGLYCEMIC SUBSTANCES...

来源:Hazardous Substances Data Bank (HSDB)

代谢

磺酰脲类药物在胃肠道快速吸收，在血液中以高度与蛋白质结合的复合物形式运输，并经历广泛的肝脏代谢（除氯磺丙脲外）。磺酰脲类药物在肝脏代谢和残余清除方面存在很大差异，这些因素倾向于改变稳态血清水平。代谢物可能具有活性，因此父母药物的血浆半衰期和遇到的低血糖程度之间可能存在差异。/磺酰脲/

Sulfonylureas are rapidly absorbed from the gastrointestinal tract, transported in the blood in highly protein-bound complexes, and subjected to extensive hepatic metabolism (except for chlorpropamide). Wide variation exists among the sulfonylureas in hepatic metabolism and remnal clearance, factors that tend to alter the steady-state serum levels. Metabolites may be active, so there may be a variation between the plasma half-life of the parent drug and the degree of hypoglycemia encountered. /Sulfonylurea/

来源:Hazardous Substances Data Bank (HSDB)

代谢

在肾功能衰竭中，活性代谢物可能会积累。

Active metabolites may accumulate in renal failure. /from table/

来源:Hazardous Substances Data Bank (HSDB)

代谢

尽管妥拉唑胺的确切代谢命运尚未明确建立，但该药物在大约肝脏中被代谢为两种羟基代谢物，对甲苯磺酰胺，对羧基妥拉唑胺和一个未识别的代谢物；其中几种代谢物具有药理活性。妥拉唑胺主要以代谢物的形式从尿液中排出；少量药物未发生改变，直接从尿液中排出。

Although the exact metabolic fate of tolazamide has not been clearly established, the drug is metabolized, probably in the liver, to two hydroxymetabolites, p-toluenesulfonamide, p-carboxytolazamide, and an unidentified metabolite; several of these metabolites are pharmacologically active. Tolazamide is excreted in urine principally as metabolites; small amounts are excreted in urine unchanged.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

磺酰脲类药物可能结合到胰腺细胞表面的ATP敏感的钾通道受体上，减少钾离子电导，导致细胞膜去极化。去极化通过激活电压敏感的钙通道，刺激钙离子流入，提高细胞内钙离子浓度，从而诱导胰岛素的分泌或胞吐作用。

Sulfonylureas likely bind to ATP-sensitive potassium-channel receptors on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Depolarization stimulates calcium ion influx through voltage-sensitive calcium channels, raising intracellular concentrations of calcium ions, which induces the secretion, or exocytosis, of insulin.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 药物性肝损伤

复方：妥拉唑啉

Compound:tolazamide

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

药物性肝损伤标注：低药物性肝损伤关注

DILI Annotation:Less-DILI-Concern

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

严重程度等级：2

Severity Grade:2

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

毒理性

• 药物性肝损伤

“标签部分：不良反应”

Label Section:Adverse reactions

来源:Drug Induced Liver Injury Rank (DILIrank) Dataset

吸收、分配和排泄

• 吸收

从胃肠道快速且良好地吸收。

Rapidly and well absorbed from the gastrointestinal tract.

来源:DrugBank

吸收、分配和排泄

• 消除途径

妥拉唑胺被代谢成五种主要代谢物，其降血糖活性从0%到70%不等。它们主要在尿液中排出。

Tolazamide is metabolized to five major metabolites ranging in hypoglycemic activity from 0% to 70%. They are excreted principally in the urine.

来源:DrugBank

吸收、分配和排泄

口服给药后，血浆峰值浓度在4-8小时内达到最高。

AFTER ORAL ADMIN PEAK PLASMA LEVELS REACH PEAK IN 4-8 HR.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

甲磺丁脲吸收缓慢；低血糖作用在4-6小时后开始，并在单次剂量后持续显著水平达15小时。甲磺丁脲被代谢为多种低血糖物质，这些物质主要通过肾脏排出。

TOLAZAMIDE IS SLOWLY ABSORBED; ONSET OF HYPOGLYCEMIC ACTION OCCURS @ 4-6 HR & PERSISTS @ SIGNIFICANT LEVEL UP TO 15 HR AFTER SINGLE DOSE. TOLAZAMIDE IS METABOLIZED TO NUMBER OF HYPOGLYCEMIC SUBSTANCES THAT ARE LARGELY EXCRETED BY KIDNEY.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

一些具有中等活性的代谢物通过肾脏排出。/来自表格/

Some metabolites with moderate activity excreted via kidney. /from table/

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  Xn
• 安全说明：
  S36
• 危险类别码：
  R22
• WGK Germany：
  3
• 海关编码：
  2935009090
• RTECS号：
  YT4400000
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302
• 储存条件：
  Refrigerator

SDS

---

SECTION 1: Identification of the substance/mixture and of the company/undertaking
Product identifiers
Product name : Tolazamide
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. : 1156-19-0
Relevant identified uses of the substance or mixture and uses advised against
Identified uses : Laboratory chemicals, Manufacture of substances

---

SECTION 2: Hazards identification
Classification of the substance or mixture
Not a hazardous substance or mixture according to Regulation (EC) No. 1272/2008.
This substance is not classified as dangerous according to Directive 67/548/EEC.
Label elements
The product does not need to be labelled in accordance with EC directives or respective national laws.
Other hazards - none

---

SECTION 3: Composition/information on ingredients
Substances
Synonyms : 1-(Hexahydro-1H-azepin-1-yl)-3-(p-toluenesulfonyl)urea
Formula : C14H21N3O3S
Molecular Weight : 311,40 g/mol
CAS-No. : 1156-19-0
EC-No. : 214-588-3
No components need to be disclosed according to the applicable regulations.

---

SECTION 4: First aid measures
Description of first aid measures
If inhaled
If breathed in, move person into fresh air. If not breathing, give artificial respiration.
In case of skin contact
Wash off with soap and plenty of water.
In case of eye contact
Flush eyes with water as a precaution.
If swallowed
Never give anything by mouth to an unconscious person. Rinse mouth with water.
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

---

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), Sulphur oxides
Advice for firefighters
Wear self contained breathing apparatus for fire fighting if necessary.
Further information
no data available

---

SECTION 6: Accidental release measures
Personal precautions, protective equipment and emergency procedures
Avoid dust formation. Avoid breathing vapours, mist or gas.
For personal protection see section 8.
Environmental precautions
Do not let product enter drains.
Methods and materials for containment and cleaning up
Sweep up and shovel. Keep in suitable, closed containers for disposal.
Reference to other sections
For disposal see section 13.

---

SECTION 7: Handling and storage
Precautions for safe handling
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.
Specific end use(s)
A part from the uses mentioned in section 1.2 no other specific uses are stipulated

---

SECTION 8: Exposure controls/personal protection
Control parameters
Components with workplace control parameters
Exposure controls
Appropriate engineering controls
General industrial hygiene practice.
Personal protective equipment
Eye/face protection
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
Choose body protection in relation to its type, to the concentration and amount of dangerous
substances, and to the specific work-place., The type of protective equipment must be selected
according to the concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection
Respiratory protection is not required. Where protection from nuisance levels of dusts are desired,
use type N95 (US) or type P1 (EN 143) dust masks. 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.

---

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- no data available
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

---

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
no data available
Hazardous decomposition products
Other decomposition products - no data available
In the event of fire: see section 5

---

SECTION 11: Toxicological information
Information on toxicological effects
Acute toxicity
LD50 Oral - rat - > 5.000 mg/kg
Skin corrosion/irritation
no data available
Serious eye damage/eye irritation
no data available
Respiratory or skin sensitisation
no data available
Germ cell mutagenicity
rat
Liver
DNA damage
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
no data available
Specific target organ toxicity - repeated exposure
no data available
Aspiration hazard
no data available
Additional Information
RTECS: YT4400000

---

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

---

SECTION 13: Disposal considerations
Waste treatment methods
Product
Offer surplus and non-recyclable solutions to a licensed disposal company.
Contaminated packaging
Dispose of as unused product.

---

SECTION 14: Transport information
UN number
ADR/RID: - IMDG: - IATA: -
UN proper shipping name
ADR/RID: Not dangerous goods
IMDG: Not dangerous goods
IATA: Not dangerous goods
Transport hazard class(es)
ADR/RID: - IMDG: - IATA: -
Packaging group
ADR/RID: - IMDG: - IATA: -
Environmental hazards
ADR/RID: no IMDG Marine pollutant: no IATA: no
Special precautions for user
no data available

---

---

SECTION 15 - REGULATORY INFORMATION
N/A

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

用途

妥拉磺脲是一种中效磺酰脲衍生物，属于第一代口服降糖药。其作用机制与醋酸己己脲相似。在治疗初期，妥拉磺脲主要通过刺激胰腺分泌和释放胰岛素来降低血糖水平。长期使用时，尽管药物对胰岛素分泌的促进作用逐渐减弱，但仍然能有效控制血糖。其长期降糖的具体机制尚不明确，可能涉及胰腺外的作用。

药物相关作用

妥拉磺脲与磺胺类、水杨酸类、保泰松、吲哚美辛、香豆素、青霉胺和丙磺舒等药物合用时，可增强其降糖效果，导致低血糖反应。同时，与大剂量肾上腺皮质激素、甲状腺素、口服避孕药、呋塞米及噻嗪类利尿剂合用，则会减弱妥拉磺脲的降糖作用。

药性与应用

妥拉磺脲是一种磺脲类口服降糖药。它对正常人和糖尿病患者均有降糖效果，但对胰岛功能完全丧失者无效。其主要通过刺激β细胞释放胰岛素来降低血糖水平。药物吸收缓慢，在4～6小时后开始起效，并持续10～14小时。肝脏代谢后，经肾脏排出。

临床主要用于成年后发病、单用饮食控制无效且保留一定胰岛功能的轻中型糖尿病患者。对于胰岛素耐受者，妥拉磺脲可以辅助治疗，减少胰岛素用量。此外，由于其具有轻微利尿作用，更适合于有尿潴留倾向的患者。

生物活性

Tolazamide 是一种口服降血糖剂，用于研究2型糖尿病的生物活性。

反应信息

• 作为反应物：
  描述：

  妥拉磺脲 在 potassium dihydrogenphosphate 、 溶剂黄146 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 14.0h， 以11%的产率得到3,3-Hexamethylen-1-(4-tolylsulfonyl)-triazen
  参考文献：
  名称：

  肼衍生物的亚硝化，第 6 版：磺酰氨基脲类口服降糖药在亚硝化条件下的新反应

  摘要：

  根据一种新的反应过程，在温和的亚硝化条件下，包括几乎生理学的体外条件下，磺酰氨基脲类型的口服抗糖尿病药，如托拉唑胺 (1) 和格列索吡 (2)，被转化为磺酰三氮唑 3a、b。具有 N4 酰基氨基脲结构 4 的模型化合物显示出不同的反应行为，除了亚硝胺 6 外，还形成了酰胺 5。

  DOI：

  10.1002/ardp.19933261203
• 作为产物：
  描述：

  对甲基苯磺酰异氰酸酯 、 1-氨基高哌啶 以 二氯甲烷 为溶剂， 以77%的产率得到妥拉磺脲
  参考文献：
  名称：

  一种磺酰脲类化合物的合成方法

  摘要：

  本发明公开了一种磺酰脲类化合物的合成方法，包括如下步骤：将对甲苯磺酰异氰酸酯和氨基化合物分别溶于有机溶剂中，得到对甲苯磺酰异氰酸酯有机溶液和氨基化合物有机溶液；在氮气和/或惰性气体保护下，将氨基化合物有机溶液滴加到对甲苯磺酰异氰酸酯有机溶液中进行反应；待反应结束，旋蒸去除溶剂、除杂，得到所述磺酰脲类化合物；本发明上述合成方法通过特定原料选择，能够在室温下制备得到磺酰脲类化合物，减少了能耗，同时，该合成方法操作简单，合成产物易于分离，而且产物纯度较高。

  公开号：

  CN113683584A

文献信息

• [EN] ACC INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE L'ACC ET UTILISATIONS ASSOCIÉES
  申请人：GILEAD APOLLO LLC

  公开号：WO2017075056A1

  公开（公告）日：2017-05-04

  The present invention provides compounds I and II useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same.

  本发明提供了化合物I和II，这些化合物可用作乙酰辅酶A羧化酶（ACC）的抑制剂，以及它们的组合物和使用方法。
• SULFOXIMINE SUBSTITUTED QUINAZOLINES FOR PHARMACEUTICAL COMPOSITIONS
  申请人：BLUM Andreas

  公开号：US20140135309A1

  公开（公告）日：2014-05-15

  This invention relates to novel sulfoximine substituted quinazoline derivatives of formula I wherein Ar, R 1 and R 2 are as defined herein, and their use as MNK1 (MNK1a or MNK1b) and/or MNK2 (MNK2a or MNK2b) kinase inhibitors, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment or amelioration of MNK1 (MNK1a or MNK1b) and/or MNK2 (MNK2a or MNK2b) mediated disorders.

  这项发明涉及公式I的新型磺酰胺取代的喹唑啉衍生物，其中Ar、R1和R2如本文所定义，并且它们作为MNK1（MNK1a或MNK1b）和/或MNK2（MNK2a或MNK2b）激酶抑制剂的用途，含有这些化合物的药物组合物，以及将其用作治疗或改善MNK1（MNK1a或MNK1b）和/或MNK2（MNK2a或MNK2b）介导的疾病的药剂的方法。
• [EN] SULFOXIMINE SUBSTITUTED QUINAZOLINES FOR PHARMACEUTICAL COMPOSITIONS<br/>[FR] QUINAZOLINES SUBSTITUÉES PAR SULFOXIMINE POUR COMPOSITIONS PHARMACEUTIQUES
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2014072244A1

  公开（公告）日：2014-05-15

  This invention relates to novel sulfoximine substituted quinazoline derivatives of formula (I), wherein Ar, R1 and R2 are as defined in the description and claims, and their use as MNK1 (MNK1a or MNK1b) and/or MNK2 (MNK2a or MNK2b) kinase inhibitors, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment or amelioration of MNK1 (MNK1a or MNK1b) and/or MNK2 (MNK2a or MNK2b) mediated disorders.

  这项发明涉及一种新型的配方(I)的磺酰胺取代喹唑啉衍生物，其中Ar、R1和R2如描述和声明中所定义，并且它们作为MNK1（MNK1a或MNK1b）和/或MNK2（MNK2a或MNK2b）激酶抑制剂的用途，含有这些化合物的药物组合物，以及将其用作治疗或改善MNK1（MNK1a或MNK1b）和/或MNK2（MNK2a或MNK2b）介导的疾病的药剂的方法。
• NOVEL GLUCOKINASE ACTIVATORS AND METHODS OF USING SAME
  申请人：Ryono Denis E.

  公开号：US20080009465A1

  公开（公告）日：2008-01-10

  Compounds are provided which are phosphonate and phosphinate activators and thus are useful in treating diabetes and related diseases and have the structure wherein is a heteroaryl ring; R 4 is —(CH 2 ) n -Z-(CH 2 ) m —PO(OR 7 )(OR 8 ), —(CH 2 ) n Z-(CH 2 ) m —PO(OR 7 )R g , —(CH 2 ) n -Z-(CH 2 ) m —OPO(OR 7 )R g , —(CH 2 ) n Z—(CH 2 ) m —OPO(R 9 )(R 10 ), or —(CH 2 ) n Z—(CH 2 ) m —PO(R 9 )(R 10 ); R 5 and R 6 are independently selected from H, alkyl and halogen; Y is R 7 (CH 2 ) s or is absent; and X, n, Z, m, R 4 , R 5 , R 6 , R 7 , and s are as defined herein; or a pharmaceutically acceptable salt thereof. A method for treating diabetes and related diseases employing the above compounds is also provided.

  提供了磷酸酯和磷酸酯激活剂，因此在治疗糖尿病和相关疾病方面非常有用，并具有以下结构： 其中 是杂环芳基环； R 4 为—(CH 2 ) n -Z-(CH 2 ) m —PO(OR 7 )(OR 8 )、—(CH 2 ) n Z-(CH 2 ) m —PO(OR 7 )R g 、—(CH 2 ) n -Z-(CH 2 ) m —OPO(OR 7 )R g 、—(CH 2 ) n Z—(CH 2 ) m —OPO(R 9 )(R 10) 或—(CH 2 ) n Z—(CH 2 ) m —PO(R 9 )(R 10) ； R 5 和R 6 分别选择自H、烷基和卤素； Y为R 7 (CH 2 ) s 或不存在；以及 X、n、Z、m、R 4 、R 5 、R 6 、R 7 和s如本文所定义；或其药用盐。 还提供了一种利用上述化合物治疗糖尿病和相关疾病的方法。
• [EN] HETEROCYCLIC COMPOUNDS FOR THE TREATMENT OF STRESS-RELATED CONDITIONS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES POUR LE TRAITEMENT D'ÉTATS LIÉS AU STRESS
  申请人：OTSUKA PHARMA CO LTD

  公开号：WO2010137738A1

  公开（公告）日：2010-12-02

  The present invention provides a novel heterocyclic compound. A heterocyclic compound represented by general formula (1) wherein, R1 and R2, each independently represent hydrogen; a phenyl lower alkyl group that may have a substituent(s) selected from the group consisting of a lower alkyl group and the like on a benzene ring and/or a lower alkyl group; or a cyclo C3-C8 alkyl lower alkyl group; or the like; R3 represents a lower alkynyl group or the like; R4 represents a phenyl group that may have a substituent(s) selected from the group consisting of a 1,3,4-oxadiazolyl group that may have e.g., halogen or a heterocyclic group selected from pyridyl group and the like; the heterocyclic group may have at least one substituent(s) selected from a lower alkoxy group and the like or a salt thereof.

  本发明提供了一种新颖的杂环化合物。一种由通式（1）表示的杂环化合物，其中，R1和R2分别独立表示氢；苯基较低烷基基团，可能在苯环和/或较低烷基基团上具有从较低烷基基团等组成的取代基；或环C3-C8烷基较低烷基基团；或类似物；R3表示较低炔基基团或类似物；R4表示可能具有从1,3,4-噁二唑基团（例如，卤素）或从吡啶基团等组成的取代基的苯基团；所述杂环基可能具有至少一个从较低烷氧基等选择的取代基或其盐。