Identification and quantitation of a benzoylindole (2-methoxyphenyl)(1-pentyl-1H-indol-3-yl)methanone and a naphthoylindole 1-(5-fluoropentyl-1H-indol-3-yl)-(naphthalene-1-yl)methanone (AM-2201) found in illegal products obtained via the Internet and their cannabimimetic effects evaluated by in vitro [35S]GTP��S binding assays

During our careful surveillance of unregulated drugs in January to February 2011, we found two new compounds used as adulterants in herbal products obtained via the Internet. These compounds were identified by liquid chromatography?Cmass spectrometry, gas chromatography-mass spectrometry, accurate mass spectrometry, and nuclear magnetic resonance spectroscopy. The first compound identified was a benzoylindole (2-methoxyphenyl)(1-pentyl-1H-indol-3-yl)methanone (1), which is a positional isomer of (4-methoxyphenyl)(1-pentyl-1H-indol-3-yl)methanone (RCS-4, 4). The second compound was 1-(5-fluoropentyl-1H-indol-3-yl)-(naphthalene-1-yl)methanone (AM-2201, 2). The compound 2 has been reported to be a cannabinoid receptor agonist. Because the cannabimimetic effects of compounds 1 and 4 have not been reported to date, their biological activities were evaluated by measuring the activation of [³⁵S] guanosine-5??-O-(3-thio)-triphosphate binding to guanine nucleotide-binding proteins, together with those of other synthetic cannabimimetic compounds. For quantitation of the above two compounds (1 and 2) and previously identified compounds (AM-694, 3; JWH-122, 5; RCS-4, 4), each product was extracted with methanol under ultrasonication to prepare a sample solution for analysis by liquid chromatography with ultraviolet detection. Each of four commercial products contained some of cannabimimetic indoles 1?C5; their contents ranged from 14.8 to 185 mg per pack.     

Analysis of azepane isomers of AM-2233 and AM-1220, and detection of an inhibitor of fatty acid amide hydrolase [3′-(aminocarbonyl)(1,1′-biphenyl)-3-yl]-cyclohexylcarbamate (URB597) obtained as designer drugs in the Tokyo area

During our careful survey of unregulated drugs from November 2011 to January 2012 in the Tokyo area, we found two new compounds in commercial products. The first was identified as the benzoylindole (2-iodophenyl)[1-(1-methylazepan-3-yl)-1H-indol-3-yl]methanone (2), which is the azepane isomer of AM-2233 (1). Compound 2 was isolated by silica gel column chromatography, and was identified through a combination of liquid chromatography–mass spectrometry, gas chromatography–mass spectrometry, accurate mass spectrometry, and nuclear magnetic resonance spectroscopy. The second compound was identified as [3′-(aminocarbonyl)(1,1′-biphenyl)-3-yl]-cyclohexylcarbamate (URB597, 5) by comparing analytical data with that of the authentic compound. For quantitation of these three compounds, each commercial product was extracted with methanol under ultrasonication to prepare the solution for analysis by liquid chromatography with ultraviolet detection. The occurrence of compounds 1 and 2, and AM-1220 (3) and its azepane isomer (4) in 29 commercial products found in the Tokyo area are also shown in this report.     

多选题(MCQs in Radiology)(连载)

4.31 Sprengel's肩A.总是发生在单侧B.伴有臂骨发育不全C.伴发先天性短颈畸形D.肩胛抬高但不旋转E.锁骨不受累4.32 下列有关血管瘤的描述是正确的     

1例46,xy,-18, del(18)(p~(ter)→q22,3:)报告

患儿,男,7个月,因感冒、发烧、抽搐入院。患儿系第一胎,其母孕7~ 月时,因急腹症行剖腹产。初生儿体重2350g,自然啼哭。5~ 月前吃奶好,不爱哭,近2~ 月夜间频繁啼哭。此次因感冒、发烧、抽搐于1994年8月28日夜间急诊入儿科治疗。 检查:反应迟钝,头大,扁园(前后径小,左右径大),双眼距宽,鼻梁塌,鲤鱼嘴,双耳低位。颈软、未扪及包块。胸廓正常,腹部平坦,未扪及包块。生殖器发育不良,阴茎短小,如小黄豆大小,阴囊肿大透明。四肢瘦小,四肢张力降低,手握力差,右手呈握笔状,双手呈桥贯掌,atd角高。双下肢无力,被动活动好,足背淋巴回流不畅,大脚趾背屈明显。     

放射学多选题(MCQS in Radiology)(连载)

6.内分泌疾病6.1 在检查Cushing 综合征时,下列试验很可能区别起因是垂体还是肾上腺A.侧位头颅X 线摄影B.血浆促肾上腺皮质激数测定     

~3H-氟甲膦酸异丙酯(异丙基-1-~3H)(沙林)的合成

本文报导用~3H-异丙醇(1-~3H)、甲膦酰二氯和氟化钠,在二氯甲烷中回流反应,制备了~3H-氟甲膦酸异丙酯。氟甲膦酸异丙酯(沙林)是外军早已装备的致死性神经毒剂,为了进一步研究其中毒机制,以寻找有效防治药物,我们合成了~3H-氟甲膦酸异丙酯(异丙基-1-~3H)。     

放射学多选题(MCQs in Radiology)(连载)

4.骨与关节4.1 下列是骨髓硬化症的特征表现A.长骨两端骨膜反应B.颅穹窿不受累C.骨内可见透光区D.先前就存在红细胞增多症     

放射学多选题(MCQs in Radiology)(连载)

1.31 单侧肺气肿(Macleod氏综合征) A.患肺透明度高B.患肺通常较正常肺小C.呼气时受阻不是其特征D.肿灌注扫描一般正常     

放射学多选题(MCQs in Radiology)(连载)

7.神经放射学7.1 下列表现有助于颅底骨折的诊断A.松果体移位B.耳脑脊液溢C.一侧乳突气房混浊D.蝶窦内有气液面E.颅内积气     

放射学多选题(MCQs in Radiology)(连载)

神经放射攀120 Klippel一Feil‘s(先天性短颈)综合征 表现包括: (a)脊髓空洞症 (b)Sprengel‘s(翼状肩脾)畸形 (c)颈椎间舟突出发生率增高 (d)融合处推间孔丧失 (e)胸椎融合玲1蜻节性硬化特点有:二‘ (a)伴发巨细胞星形细胞瘤 (b)胃肠道出血 (c)骨硬化病灶 (d)掌骨骨膜反应 (e)伴发心脏横纹肌瘤122在前后位颈椎脊脸遭影影像中,脊谧扩 张可因为: (a)椎间盘突出 (b)室管膜瘤 (。)脊髓房 (d)骨髓瘤 (e)放射线治疗123以神经病关萦为并发症者有: (a)脊髓辛洞症 (b)糖尿病 ‘(c)神经纤维瘤病-.: (d)脊髓灰质炎‘· (e)进行性肌汽含美不良卜124形…     

放射学多选题(MCQs in Radiology)(连载)

二、心血管系统2.1左心缘肺动脉段下的膨凸(第一弓)是 下列疾病的特征 A.由于血栓栓塞而引起的肺动脉 高压 B.瓦耳萨耳瓦窦动脉瘤 C.二尖瓣狭窄 D。反位 E Ebstein夕s畸形2 .2瓦耳萨耳瓦窦动脉瘤 A.右冠状窦动脉瘤凸入右心房 B.左冠状窦动脉瘤凸入左心房 C。破裂进入左心房最常见 D。破裂进入心包腔是公认的危险 E。病变一般是由霉菌感染所致2。3下列征象认为是法洛氏四联症术后合 并症 A.吻合术对侧肋骨切迹 B。单侧肺水肿 C。右心室流出道钙化 D。肺动脉高压 E。右心室流出道动脉瘤2.4下列描述是正确的 A。心内膜纤维弹性组织增生…     

放射学多选题(MCQs in Radiology)(连载)

3.31 普遍认为蛔虫感染是下列疾病的原因A.黄疸B.肠扭转C.溃疡性十二指肠炎     

Spectroscopic characterization and crystal structures of two cathinone derivatives: 1-(4-chlorophenyl)-2-(1-pyrrolidinyl)-pentan-1-one (4-chloro-α-PVP) sulfate and 1-(4-methylphenyl)-2-(dimethylamino)-propan-1-one (4-MDMC) hydrochloride salts,seized on illicit drug market

Purpose

Two compounds newly found in the seizures by drug enforcement agencies were identified and characterized by various instrumental analytical methods.

Methods

The obtained powder samples were analyzed by gas chromatography–mass spectrometry (GC–MS), liquid chromatography–mass spectrometryⁿ (LC–MSⁿ), nuclear magnetic resonance (NMR) spectroscopy, infrared and Raman spectroscopy and X-ray crystallography.

Results

The two compounds were tentatively identified as 4-chloro-α-PVP and 4-MDMC by GC–MS, and LC–MS/MS. The confirmation of the results was made by NMR spectroscopy. The X-ray crystallography gave information that 4-chloro-α-PVP and 4-MDMC were in salted forms with sulfate and hydrochloride, respectively; in addition, both compounds existed as racemic mixtures.

Conclusions

We could identify 4-chloro-α-PVP and 4-MDMC in the seizure powder samples by various analytical methods. X-ray crystallography was especially useful for identifying the salted forms and enantiomeric forms.

     

肉样瘤病(Sarcoidosis)(附3例报告)

肉样瘤病又称结节病,是一种原因未明少见的慢性肉芽肿病,可侵及皮肤和多数内部器官。1869年Jonathan Hutchin son描述了它的组织学特征。近年来国内陆续有报告,现将我们见到的3例报告如下,并对其病因,临床表现、诊断和治疗略加讨论。     

3-(2′-[18F]fluoroethyl)spiperone,a potent dopamine antagonist: Synthesis,structural analysis and in-vivo utilization in humans

The synthesis of 3-(2′-[¹⁸F]fluoroethyl)spiperone (1c), a radiotracer useful for imaging the brain dopamine receptor system in vivo using positron emission tomography, is described. Precursors of 1c, the functional 3-N-alkyl derivatives of spiperone (4), were prepared by the alkylation of the amide group in spiperone (2a) by 1,2-disubstituted ethanes under phase transfer conditions. A comprehensive evaluation of the reaction of the derivatives 4a–h with no-carrier-added K ¹⁸F/Kryptofix clearly indicated that the ketalized derivatives 4e–h were the choice of the precursors for 1c. The i.r., MS and NMR spectral data suggested that under phase transfer reaction conditions, the amide nitrogen was preferentially alkylated. To provide a firm basis for comparison with related analogues, an x-ray analysis was performed on a single crystal of 3-(2′-fluoroethyl)spiperone (1d). The tomographic behavior of 1c in human brain tissue was measured for more than 7 h and was consistent with the labeling of dopamine D-2 receptors.     

The Bücherer-Strecker synthesis of d- and l-(1-11C)tyrosine and the in vivo study of l-(1-11C)tyrosine in human brain using positron emission tomography

The synthesis of d-and l-(1-¹¹C)tyrosine, starting with ¹¹C-cyanide, is reported. dl-(1-¹¹C)Tyrosine was prepared by the Bücherer-Strecker reaction, from carrier added ¹¹C-cyanide with an incorporation of 80% in 20 min. The isolation of the pure d- and l-amino acid isomers from the enantiomeric mixture was accomplished within 15 min by preparative HPLC using a chiral stationary phase and a phosphate buffer as the mobile phase. Typically, the total synthesis time was 50 min (including purification) from end of trapping of ¹¹C-cyanide, with a radiochemical yield of d- and l-amino acid of 40%–60%. The d- and l-(1-¹¹C)tyrosine were both obtained optically pure, with a carrier added specific activity of 0.3–0.5 Ci/mmol and a radiochemical purity better than 99%. The ¹¹C labelled l-tyrosine was used in an in vivo study in the human brain using positron emission tomography (PET).     

一维链状聚合阴离子[Mo_xAg_xS_(4x)]_n~(x-)(x=1-3)的电子结构研究

用ＥＨＴ方法对系列含聚合阴离子［ ＭｏｘＡｇｘＳ４ ｘ］ ｎｘ － （ｘ ＝ １ － ３） 的一维链状金属配位聚合物进行了能带结构计算,着重探讨了它们的能带结构、成键作用,并且还对它们电子光谱和导电机理进行了研究     

46,XX,t(6,7)(q25;q11)导致胎儿发育不良1例

患者。女。34岁，汉族，孕3流3。其结婚8年避孕，第9年第1次怀孕。于孕3个月无明显诱因自然流产；半年后，第2次怀孕。孕4个月，B超示胎儿不发育，胎龄仅1个月大小。行人工流产术。1年后，第3次怀孕，孕5个月，B超检查胎儿仍不发育。行人工流产术。患者自述月经规律。孕期无药物及射线接触史，夫妇非近亲结婚，其丈夫无烟酒嗜好，家系调查。患者的外祖母孕7产4，有3次流产史。     

Synthesis, radioiodination and in vitro and in vivo sigma receptor studies of N-1-allyl-N´-4-phenethylpiperazine analogs

IntroductionSigma-1 (σ₁) receptor radioligands are useful for basic pharmacology studies and for imaging studies in neurology, psychiatry and oncology. We derived a hybrid structure, N-1-allyl-N´-4-phenethylpiperazine, from known ligands TPCNE and SA4503 for use as a scaffold for development of radioiodinated σ₁ receptor ligands.MethodsE-and Z-N-1-(3′-iodoallyl)-N´-4-(3″,4″-dimethoxyphenethyl)-piperazine (E-1 and Z-1), N-1-allyl-N´-4-(3′,4′-dimethoxyphenethyl)-piperazine (2) and E-N-1-(3′-iodoallyl)-N´-4-(3″-methoxy-4′´-hydroxyphenethyl)-piperazine (3) were synthesized. Affinities for σ₁ and σ₂ receptors were determined. [¹²⁵I]E-1 and [¹²⁵I]Z-1 were prepared and evaluated in vivo in mice. [¹²⁵I]E-1 was further evaluated in σ₁ receptor binding assays in vitro.ResultsE-1 displayed moderately high apparent affinity (15 nM) for σ₁ sites and 84-fold selectivity against σ₂ sites. Z-1 showed similar σ₁ affinity, but only 23-fold selectivity. In contrast, 2 exhibited poor binding to both subtypes, while 3 had good affinities but poor selectivity. E-1 profiled as a probable antagonist in the phenytoin shift assay. [¹²⁵I]E-1 and [¹²⁵I]Z-1 were prepared in good yields and with high specific radioactivities. Log D_7.4 values (2.25 and 2.27) fall within the optimal range for in vivo studies. Both radioligands selectively labeled σ₁ receptors in mouse brain and peripheral organs in vivo. [¹²⁵I]E-1 showed a higher level of specific binding than [¹²⁵I]Z-1 and displayed good metabolic stability. Further, [¹²⁵I]E-1 selectively labeled σ₁ receptors in mouse brain homogenates (K_d 3.79 nM; B_max=599 fmol/mg protein).Conclusions[¹²⁵I]E-1 is a selective σ₁ receptor radioligand that exhibits properties amenable to in vitro and in vivo studies, with possible extension to single photon emission computed tomography using iodine-123.     

Fluorinated benzamide neuroleptics—2. Synthesis and radiosynthesis of (S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-(3-[18F]fluoropropyl)-3-substituted-2-methoxybenzamides

Synthesis of a fluorinated benzamide neuroleptic, (S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-(3-fluoropropyl)-2,3-dimethoxybenzamide starting from 3-(3,4-dimethoxyphenyl)-1-propanol in 20–25% overall yield is reported. Radiosynthesis of (S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-(3[¹⁸F]fluoropropyl)-2-methoxybenzamide([¹⁸F]FPHB) and (S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-(3[¹⁸F]fluoropropyl)-2,3-dimethoxybenzamide([¹⁸F]FPHB) was carried out by nucleophilic substitution reaction of (S)-N-[(1-ethyl-2-pyrrolidinyl)methyl-5-(3-tosyloxypropyl)-2-methoxybenzamide and (S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-(3-tosyloxypropyl)-2,3-dimethoxybenzamide respectively, with no carrier added [¹⁸F]fluoride. Both, [¹⁸F]FPHB and [¹⁸F]FPHB were obtained in approx. 20–30% yields (EOS/EOB, decay corrected). Specific activities of 900–1700 Ci/mmol for [¹⁸F]FPHB and 800–1400 Ci/mmol for [¹⁸F]FPMB were obtained by reverse phase HPLC purification. Total synthesis and purification time required for either [¹⁸F]FPHB or [¹⁸F]FPMB was 120 min from EOB.