6-nitro-1-naphthoic acid | 1975-45-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 6-nitro-1-naphthoic acid
• 英文别名: 6-nitro-[1]naphthoic acid；6-Nitro-[1]naphthoesaeure；6-nitro-1-naphthalenecarboxylic acid；6-nitronaphthalene-1-carboxylic acid；6-Nitro-naphthalincarbonsaeure-(1)；6-Nitro-naphthoesaeure-(1)；1-Naphthalenecarboxylic acid, 6-nitro-
• CAS: 1975-45-7
• 化学式: C₁₁H₇NO₄
• 分子量: 217.181
• InChiKey: KGERWIYNIIBKLA-UHFFFAOYSA-N

物化性质

• 熔点：
  227-227.5 °C
• 沸点：
  461.9±18.0 °C(Predicted)
• 密度：
  1.468±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-nitro-1-naphthoic acid 在 palladium on activated charcoal sodium azide 、 硫酸 、 氢气 作用下， 以 乙醇 、 paraffin 为溶剂， 生成 5-Fluor-2-cyan-naphthalin
  参考文献：
  名称：

  Substituent Effects. VIII.¹ Synthesis of Substituted α- and β-Fluoronaphthalenes²

  摘要：

  DOI：

  10.1021/ja00978a038
• 作为产物：
  描述：

  methyl 6-nitro-1-naphthoate 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以100%的产率得到6-nitro-1-naphthoic acid
  参考文献：
  名称：

  (Aminoalkyl)indole Isothiocyanates as Potential Electrophilic Affinity Ligands for the Brain Cannabinoid Receptor

  摘要：

  A series of (aminoalkyl)indole compounds, naphthalene analogs of pravadoline (1), has been shown to exhibit cannabinoid agonist activities such as antinociception in animals, inhibition of adenylate cyclase in brain membranes, and binding to the cannabinoid receptor. These pravadoline analogs were selected for the preparation of potential electrophilic affinity ligands based on the synthesis of isothiocyanate derivatives. One isothiocyanatonaphthalene derivative (8) displaced [H-3]CP-55940 binding to a rat brain P2 membrane preparation with an IC50 of 690 nM, which was 10-fold less potent than the parent molecule (IC50 = 73 nM). Isothiocyanate substitution at various positions on the naphthalene moiety of the desmethyl analog 10 gave compounds that displaced [H-3]CP-55940 with IC50 values between 400 and 1000 nM, compared with 46 nM for the parent compound 10. However, 6-isothiocyanato substitution on the indole ring of the desmethyl analog provided isothiocyanate 12 that displaced [H-3]CP-55940 binding with an IC50 of 160 nM. After pretreatment of brain membranes with this high-affinity isothiocyanato ligand followed by washing out the ligand, the membranes were depleted of 90% of the cannabinoid receptor binding capacity. Loss of receptor binding capacity was half-maximal at 300 nM of the derivative under standard assay conditions. As a control, pretreatment with the parent compound at concentrations that were 20 times the K-d failed to alter subsequent binding activity. This study demonstrates that an isothiocyanato (aminoalkyl)-indole (12) can behave as an affinity ligand which binds irreversibly to the cannabinoid receptor in brain and which precludes subsequent binding of the cannabinoid ligand [H-3]CP-55940.

  DOI：

  10.1021/jm950932r

文献信息

• Novel Fluorene Derivatives, Composition Containing Said Derivatives and the Use Thereof
  申请人：MAILLIET Patrick

  公开号：US20080153837A1

  公开（公告）日：2008-06-26

  This invention relates to derivatives of 4-(benzimidazol-2-yl)fluorene and 4-(azabenzimidazol-2-yl)fluorene, to pharmaceutical compositions comprising such derivatives, and to methods of treatment of disorders related to Hsp90 protein activity, comprising administering such derivatives.

  这项发明涉及4-(苯并咪唑-2-基)芴和4-(氮杂苯并咪唑-2-基)芴的衍生物，涉及包含这些衍生物的药物组合物，以及涉及治疗与Hsp90蛋白活性相关的疾病的方法，包括给予这些衍生物。
• Novel Therapies for Psoriasis
  作者：Jennifer Cather、Alan Menter

  DOI：10.2165/00128071-200203030-00003

  日期：——

  The T cell-driven immunopathogenesis of psoriasis has been well recognized since cyclosporine first revolutionized the treatment of psoriasis 20 years ago. Almost all investigative and clinical research subsequently, has concentrated on elucidating the specifics of antigen presentation, T cell interaction and the production of specific cytokines. The role of the keratinocyte, previously thought to be the primary target cell in psoriasis pathogenesis, has been relegated to a secondary role and the mechanism of action of systemic methotrexate in psoriasis has been challenged, the primary role of the T lymphocyte is now well known. While psoriasis has traditionally been treated ‘ab initio’ with topical medications (corticosteroids, vitamin D3, and retinoid derivatives), either singly, in combination, or with ultraviolet B (UVB) or psoralens and ultraviolet A (PUVA) therapy, the role of systemic medications has assumed greater prominence. Thus, three systemic medications currently are approved worldwide for the treatment of moderate to severe forms of psoriasis, namely cyclosporine, methotrexate and acitretin. The first two are likely to give significant clearing (greater than 75%) in the majority of cases, whereas acitretin is significantly less effective as monotherapy, but may approach methotrexate and cyclosporine in efficacy, if combined with PUVA or UVB phototherapy. The main limitations of these three drugs remain organ toxicity, especially hepatic toxicity with methotrexate, hypertension and nephrotoxicity with cyclosporine, and teratogenecity and mucocutaneous toxicity with acitretin. Thus, the need for more specific systemic therapy, targeting the T lymphocyte. This has become the major area of clinical research interest over the past 5 years, with the promise of longer-term disease control (improved remissions) and less organ toxicities. Currently, there are over 15 of these ‘biologic’ drugs in various stages of development and clinical trials, either by the subcutaneous, intramuscular or intravenous route. The three main variables are the rapidity of onset, percentages of improvement and remission rates. Without exception, these new systemic agents appear to be remarkably free of systemic organ toxicities (liver, renal, bonemarrow, etc.), with adverse effects being limited to mild flu-like symptoms with the anticipated increase in infections (e.g., herpes simplex) being either equal to placebo or only marginally increased. Not all these agents under evaluation give clinical responses equal to methotrexate or cyclosporine (75% or greater clearing in 75% of cases). In addition, response rates may be slower with some therapies versus others. However, the need for intermittent administration even by the injectable route, longer remissions, lack of systemic organ toxicities and the potential for safer usage in females of child-bearing age, make a compelling argument for widespread acceptance by both patients and the dermatological community. Other modalities under clinical evaluation include vitamin D and retinoid drugs, topically and systemically, with effects on nuclear receptors, as well as more specific wavelengths (308 to 311nm) of UVB phototherapy with application for more localized forms of psoriasis. For the 2 to 3% of the worldwide population of patients with psoriasis the future has never looked brighter.

  自从20年前环孢素首次彻底改变了牛皮癣的治疗以来，以T细胞驱动的免疫病理机制已被广泛认知。随后的几乎所有研究和临床试验都集中在阐明抗原呈递、T细胞相互作用和特定细胞因子的产生上。角质形成细胞曾被认为是牛皮癣病理机制中的主要靶细胞，但现在其角色已被降为次要，系统性甲氨蝶呤在牛皮癣中的作用机制也受到挑战，T淋巴细胞的主要角色现在已得到了公认。虽然牛皮癣传统上是通过外用药物（如皮质类固醇、维生素D3和类视黄醇衍生物）进行“初始”治疗，单独使用、联合使用，或与紫外线B（UVB）或光敏剂及紫外线A（PUVA）疗法结合使用，但系统性药物的作用变得越来越重要。目前，全球已批准三种系统性药物用于中重度牛皮癣的治疗，即环孢素、甲氨蝶呤和阿维A。前两者在大多数病例中可能给予显著清除（超过75%），而阿维A作为单药治疗的效果明显较差，但如果与PUVA或UVB光疗结合使用，其疗效可能接近甲氨蝶呤和环孢素。这三种药物的主要限制依然是器官毒性，尤其是甲氨蝶呤的肝毒性，环孢素的高血压和肾毒性，以及阿维A的致畸性和黏膜皮肤毒性。因此，针对T淋巴细胞的更特异性系统治疗的需求显得尤为重要。这已经成为过去五年临床研究的主要关注领域，承诺提供更长期的疾病控制（改善的缓解情况）以及更少的器官毒性。目前，已有超过15种“生物”药物在不同开发和临床试验阶段，通过皮下、肌肉或静脉注射给药。三个主要变量是起效的快速性、改善的百分比和缓解率。这些新的系统性药物在器官毒性（肝、肾、骨髓等）方面显然非常少见，副作用仅限于轻度流感样症状，预期的感染增加（如单纯疱疹）则与安慰剂相等或仅稍有增加，并非所有正在评估的药物在临床反应上都能达到甲氨蝶呤或环孢素的水平（在75%的病例中清除达到75%以上）。此外，某些疗法的反应速度可能较慢。然而，即使是通过注射途径的间歇性给药，较长的缓解期，缺乏系统性器官毒性，以及在育龄女性中潜在的更安全使用，使得这些药物得到了患者和皮肤病学界的广泛认可。其他正在临床评估的方法包括维生素D和类视黄醇药物的外用和系统用药，对核受体的影响，以及针对更局部形式的牛皮癣的特定波长（308到311nm）的UVB光疗。对于全球有2%到3%牛皮癣患者的人群来说，未来从未如此光明。
• Synthesis and structure-activity study of protease inhibitors. II. Amino- and guanidino-substituted naphthoates and tetrahydronaphthoates.
  作者：TOYOO NAKAYAMA、TOSHIYUKI OKUTOME、RYOJI MATSUI、MASATERU KURUMI、YOJIRO SAKURAI、TAKUO AOYAMA、SETSURO FUJII

  DOI：10.1248/cpb.32.3968

  日期：——

  Various amino-and guanidino-substituted naphthoates and tetrahydronaphthoates were synthesized and evaluated for inhibitory activities against trypsin, plasmin, kallikrein, thrombin and Cl esterase. Among these compounds, phenyl 4-guanidino-1-naphthoate (IIIj) and phenyl 6-guanidino-1-naphthoate (IIIl) exhibited potent and selective trypsin inhibition (IC50 : 4×10-7 and 5×10-8 M, respectively) and phenyl 7-guanidino-1, 2, 3, 4-tetrahydro-1-naphthoate (Vb) and p-ethoxycarbonylphenyl 7-guanidino-1, 2, 3, 4-tetrahydro-1-naphthoate (Vg) had selective inhibitory activities against thrombin (IC50 : 4×10-5 and 1×10-5 M, respectively).

  合成了多种氨基和氨基脲取代的萘酸酯和四氢萘酸酯，并评估了它们对胰蛋白酶、纤溶酶、激肽酶、凝血酶和C1酯酶的抑制活性。在这些化合物中，苯基4-氨基脲-1-萘酸酯（IIIj）和苯基6-氨基脲-1-萘酸酯（IIIl）表现出强效选择性的胰蛋白酶抑制（IC50：4×10^-7和5×10^-8 M，分别），而苯基7-氨基脲-1, 2, 3, 4-四氢-1-萘酸酯（Vb）和对乙氧基羧基苯基7-氨基脲-1, 2, 3, 4-四氢-1-萘酸酯（Vg）则对凝血酶具有选择性抑制活性（IC50：4×10^-5和1×10^-5 M，分别）。
• [EN] N-SUBSTITUTED NAPHTHALENE CARBOXAMIDES AS NEUROKININ-RECEPTOR ANTAGONISTS<br/>[FR] NAPHTALENE CARBOXAMIDES N-SUBSTITUES EN TANT QU'ANTAGONISTES DE RECEPTEURS DES NEUROKININES
  申请人：ZENECA LTD

  公开号：WO2000002859A1

  公开（公告）日：2000-01-20

  A compound of formula (I) wherein: R is alkyl; R1 is optionally substituted phenyl, 2-oxo-tetrahydro-1(2H)-pyrimidinyl, or 2-oxo-1-piperidinyl; R2 is hydrogen, alkoxy, alkanoyloxy, alkoxycarbonyl, alkanoylamino, acyl, alkyl, carbamoyl, N-alkylcarbamoyl, N,N-dialkylcarbamoyl where the alkyl groups are the same or different, hydroxy, thioacyl, thiocarbamoyl, N-alkylthiocarbamoyl, or N,N-dialkylthiocarbamoyl where the alkyl groups are the same or different. X¿1? and X2 are independently hydrogen or halo, provided that at least one of X1 or X2 is halo; and R?3, R4, R5, and R6¿ are independently hydrogen, cyano, nitro, trifluoromethoxy, trifluoromethyl, or alkylsulfonyl are antagonists of at least one tachykinin receptor and are useful in the treatment of depression, anxiety, asthma, pain, inflammation, urinary incontinence and other disease conditions. Processes for their preparation are described, as are compositions containing them and their use.

  化合物的化学式(I)，其中：R为烷基; R1为可选取代的苯基，2-氧代-四氢-1(2H)-嘧啶基或2-氧代-1-哌啶基; R2为氢、烷氧基、烷酰氧基、烷氧羰基、烷酰胺、烷基、氨基甲酰、N-烷基氨基甲酰、N,N-二烷基氨基甲酰，其中烷基团相同或不同，羟基、硫代酰基、硫代氨基、N-烷基硫代氨基、N,N-二烷基硫代氨基，其中烷基团相同或不同。X1和X2独立地为氢或卤素，但至少其中之一为卤素; R3、R4、R5和R6独立地为氢、氰基、硝基、三氟甲氧基、三氟甲基或烷基磺酰基，是至少一种快速激动肽受体的拮抗剂，可用于治疗抑郁症、焦虑症、哮喘、疼痛、炎症、尿失禁和其他疾病。描述了它们的制备过程，以及包含它们和它们的使用的组合物。
• Aminoethanol derivatives
  申请人：——

  公开号：US20040127574A1

  公开（公告）日：2004-07-01

  The present invention provides a pharmaceutical agent having cholesteryl ester transfer protein inhibitory action and useful as a blood lipid lowering agent and the like. The present invention relates to a compound represented by the formula 1 wherein Ar 1 is an aromatic ring group optionally having substituents, Ar 2 is an aromatic ring group having substituents, OR″ is an optionally protected hydroxyl group, R is an acyl group, R′ is a hydrogen atom or a hydrocarbon group optionally having substituents, or a salt thereof, and a pharmaceutical composition containing a compound of the formula (I) or a salt thereof or a prodrug thereof.

  本发明提供了一种具有胆固醇酯转移蛋白抑制作用的药物剂，可用作降低血脂等方面的药物。本发明涉及一种由式1表示的化合物，其中Ar1是一个带有取代基的芳香环基团，Ar2是一个带有取代基的芳香环基团，OR″是一个可选保护的羟基，R是一个酰基，R′是一个氢原子或一个可选带有取代基的碳氢基团，或其盐，以及含有式(I)的化合物或其盐或前药的药物组合物。