- Synthesis of a New Phorbazole and Its Derivatives
-
Phorbazoles are chlorinated marine alkaloids containing pyrrole, oxazole and phenol ring units, and differ in the number and positions of chlorine atoms. They are isolated from sea sponges and nudibranchs. In this work, a convenient synthetic method leading to a new phorbazole and its derivatives is developed. This synthesis of synthetic phorbazole G and its derivatives is achieved in seven steps in good overall yields of 26-52%. It involves formation of the pyrrole-oxazole skeleton followed by chlorination. The pyrrole-oxazole skeleton is synthesized from pyrrole and substituted acetophenones, and the key step involves cyclodehydration of amide intermediates to give protected oxazoles, followed by hydrolysis.
- Louglin, Wendy A.,Muderawan, I Wayan,Young, David J.
-
-
- Design, Synthesis, and Biological Evaluation of Novel 1,3-Oxazole Sulfonamides as Tubulin Polymerization Inhibitors
-
A series of novel 1,3-oxazole sulfonamides were constructed and screened for their potential to inhibit cancer cell growth. These compounds were evaluated against the full NCI-60 human tumor cell lines, with the majority exhibiting promising overall growth inhibitory properties. They displayed high specificity within the panel of leukemia cell lines versus all other lines tested. When examined in the dose-response assay, GI50 values fell within the low micromolar to nanomolar ranges. 1,3-Oxazole sulfonamide 16 displayed the best average growth inhibition, whereas the 2-chloro-5-methylphenyl and 1-naphthyl substituents on the sulfonamide nitrogen proved to be the most potent leukemia inhibitors with mean GI50 values of 48.8 and 44.7 nM, respectively. In vitro tubulin polymerization experiments revealed that this class of compounds effectively binds to tubulin and induces the depolymerization of microtubules within cells.
- Barnes, Korry L.,Sisco, Edward
-
supporting information
p. 1030 - 1037
(2021/06/28)
-
- The reaction of prop-2-ynylsulfonium salts and sulfonyl-protected β-amino ketones to epoxide-fused 2-methylenepyrrolidines and S-containing pyrroles
-
A novel divergent domino annulation reaction of prop-2-ynylsulfonium salts with sulfonyl-protected β-amino ketones has been developed, affording various epoxide-fused 2-methylenepyrrolidines and S-containing pyrroles in moderate to excellent yields. Prop-2-ynylsulfonium salts act as C2synthons in the reactions providing a promising epoxide-fused skeleton in a single operation with readily accessible starting materials.
- Jia, Tingting,Zeng, Gongruixue,Zhang, Chong,Zeng, Linghui,Zheng, Wenya,Li, Siyao,Wu, Keyi,Shao, Jiaan,Zhang, Jiankang,Zhu, Huajian
-
supporting information
p. 2657 - 2660
(2021/03/16)
-
- Improving the metabolic stability of antifungal compounds based on a scaffold hopping strategy: Design, synthesis, and structure-activity relationship studies of dihydrooxazole derivatives
-
L-amino alcohol derivatives exhibited high antifungal activity, but the metabolic stability of human liver microsomes in vitro was poor, and the half-life of optimal compound 5 was less than 5 min. To improve the metabolic properties of the compounds, the scaffold hopping strategy was adopted and a series of antifungal compounds with a dihydrooxazole scaffold was designed and synthesized. Compounds A33-A38 substituted with 4-phenyl group on dihydrooxazole ring exhibited excellent antifungal activities against C. albicans, C. tropicalis and C. krusei, with MIC values in the range of 0.03–0.25 μg/mL. In addition, the metabolic stability of compounds A33 and A34 in human liver microsomes in vitro was improved significantly, with the half-life greater than 145 min and the half-life of 59.1 min, respectively. Moreover, pharmacokinetic studies in SD rats showed that A33 exhibited favourable pharmacokinetic properties, with a bioavailability of 77.69%, and half-life (intravenous administration) of 9.35 h, indicating that A33 is worthy of further study.
- Cheng, Maosheng,Su, Xin,Sun, Nannan,Sun, Yin,Tian, Linfeng,Yin, Wenbo,Zhang, Chu,Zhao, Dongmei,Zhao, Liyu,Zhao, Shizhen,Zheng, Yang
-
-
- Design, synthesis and evaluation of novel 5-phenylthiophene derivatives as potent fungicidal of Candida albicans and antifungal reagents of fluconazole-resistant fungi
-
A series of 5-phenylthiophene derivatives with novel structures were designed and synthesized to combat the increasing incidence of susceptible and drug-resistant fungal infections. The antifungal activity of the synthesized compounds was assessed against seven susceptible strains and six fluconazole-resistant strains. It is especially encouraging that compounds 17b and 17f displayed significant antifungal activities against all tested strains. Furthermore, the potent compounds 17b and 17f could prevent the formation of fungi biofilms and 17f displayed satisfactory fungicidal activity. Preliminary mechanistic studies showed that the potent antifungal activity of compound 17f stemmed from inhibition of C. albicans CYP51. In addition, Compounds 17b and 17f were almost nontoxic to mammalian A549, MCF-7, and THLE-2 cells. These results strongly suggested that compounds 17b and 17f are promising as novel antifungal drugs.
- Cheng, Maosheng,Cui, Hengxian,Jiang, Hong,Li, Song,Liu, Lei,Su, Xin,Sun, Yin,Wu, Tianxiao,Yin, Wenbo,Zhang, Yuxin,Zhao, Dongmei,Zhao, Liyu,Zheng, Yang
-
-
- Synthesis of 2-Amino Substituted Oxazoles from α-Amino Ketones and Isothiocyanates via Sequential Addition and I2-Mediated Desulfurative Cyclization
-
Oxazol-2-amines were synthesized by annulation of α-amino ketones and isothiocyanates. This sequential synthetic process involves addition of α-amino ketones to isothiocyanates and I2-promoted desulfurative cyclization omitting isolation of the less stable thiourea intermediates. It is transition metal-free and operationally simple, providing access to a variety of 2-amino substituted oxazole derivatives under mild reaction conditions. (Figure presented.).
- Chang, Junbiao,Yu, Wenquan,Zhang, Shuangshuang,Zhao, Qiongli,Zhao, Yifei
-
supporting information
(2020/04/29)
-
- Toward a treatment of diabesity: In vitro and in vivo evaluation of uncharged bromophenol derivatives as a new series of PTP1B inhibitors
-
Protein tyrosine phosphatase 1B (PTP1B) has been considered as a validated biological target for type 2 diabetes treatment, but past endeavors to develop inhibitors of PTP1B into drugs have been unsuccessful. Two challenging aspects are selective inhibition and cell permeability. A structure-based strategy was employed to develop uncharged bromophenols as a new series of PTP1B inhibitors. The most potent compound 22 (LXQ46) inhibited PTP1B with an IC50 value of 0.190 μM, and showed remarkable selectivity over other protein tyrosine phosphatases (PTPs, 20–200 folds). In the SPR study, increasing concentrations of compound 22 led to concentration-dependent increases in binding responses, indicating that compound 22 could bind to the surface of PTP1B via noncovalent means. By treating insulin-resistant C2C12 myotubes with compound 22, enhanced insulin and leptin signaling pathways were observed. Long-term oral administration of compound 22 reduced the blood glucose level of diabetic BKS db mice. The glucose tolerance tests (OGTT) and insulin tolerance tests (ITT) in BKS db mice showed that oral administration of compound 22 could increase insulin sensitivity. In addition, long-term oral administration of compound 22 could protect mice from obesity, which was not the result of toxicity. Our pharmacokinetics results from the rat-based assays showed that orally administered compound 22 was absorbed rapidly from the gastrointestinal tract, extensively distributed to the tissues, and rapidly eliminated from the body. All these results indicate that compound 22 could serve as a qualified agent to treat type II diabetes.
- Li, Xiangqian,Xu, Qi,Li, Chao,Luo, Jiao,Li, Xiuxue,Wang, Lijun,Jiang, Bo,Shi, Dayong
-
p. 178 - 185
(2019/02/05)
-
- Combating fluconazole-resistant fungi with novel β-azole-phenylacetone derivatives
-
A series of β-azole-phenylacetone derivatives with novel structures were designed and synthesized to combat the increasing incidence of susceptible fungal infections and drug-resistant fungal infections. The antifungal activity of the synthesized compounds was assessed against five susceptible strains and five fluconazole-resistant strains. Antifungal activity tests showed that most of the compounds exhibited excellent antifungal activities against five pathogenic strains with MIC values in the range of 0.03–1 μg/mL. Compounds with R1 = 3-F substituted and 15o and 15ae exhibited moderate antifungal activities against fluconazole-resistant strains 17# and CaR with MIC values in the range of 1–8 μg/mL. Compounds with R1 = H or 2-F (such as 15a, 15o, 15p) displayed moderate to good antifungal activity against fluconazole-resistant strains 632, 901 and 904 with MIC values in the range of 0.125–4 μg/mL. Notably, 15o and 15ae exhibited antifungal activity against five susceptible strains and five fluconazole-resistant strains. Preliminary mechanistic studies showed that the potent antifungal activity of compound 15ae stemmed from inhibition of C. albicans CYP51. Compounds 15o, 15z and 15ae were nearly nontoxic to mammalian A549 cells.
- Zhao, Liyu,Sun, Nannan,Tian, Linfeng,Sun, Yin,Chen, Yixuan,Wang, Xinran,Zhao, Shizhen,Su, Xin,Zhao, Dongmei,Cheng, Maosheng
-
-
- Β - azole - phenylketo derivative and use thereof (by machine translation)
-
The invention belongs to the technical field of drug synthesis, provides such as general formula β - azole - phenylketo derivative and its stereoisomers or its pharmaceutically acceptable salt, hydrate, solvate or prodrug and their method of preparation, wherein A, B, R1 , R2 , R3 , X has the definition given in the specification. The invention of the compound provided by the superficial and deep fungus has relatively strong inhibiting activity, with the clinical use of antifungal drug compared, has high activity, low toxicity, antimicrobial spectrum and the like, can be used for preparing the antifungal drug. (by machine translation)
- -
-
Paragraph 0090-0096
(2019/04/06)
-
- Photoactivated N-Acyliminoiodinanes Applied to Amination: an ortho-Methoxymethyl Group Stabilizes Reactive Precursors
-
N-Acyliminoiodinanes were characterized for the first time by X-ray structural analysis. The ortho-methoxymethyl group and the carbonyl oxygen coordinate to the iodine atom of the iminoiodinane. Activation of the N-acyliminoiodinane was achieved by photoirradiation at 370 nm, thereby enabling reaction with various silyl enol ethers to give α-aminoketone derivatives in good to high yield. N-sulfonyliminoiodinanes bearing ortho substituents were used in photoinduced amination.
- Kobayashi, Yusuke,Masakado, Sota,Takemoto, Yoshiji
-
supporting information
p. 693 - 697
(2018/01/17)
-
- Synthetic method for 2,5-diaryloxazole compounds and anti-inflammatory pharmaceutical compounds containing the 2,5-diaryloxazole compounds
-
The present inventors have invented an effective synthesis method for a 2,5-diaryloxazole compound from a commercially available starting material. The synthesis method uses the Delepine reaction and the Robinson-Gabriel reaction as main steps. For oxazole compounds synthesized in the present invention, the present inventors have evaluated the inhibitory effect of LPS-induced NO production in RAW 264.7 cells, and have found that the oxazole compounds of the present invention significantly inhibit NO production in a concentration-dependent manner. Therefore, the oxazole compounds of the present invention may be potential compounds which can be used as anti-inflammatory agents.COPYRIGHT KIPO 2018
- -
-
Paragraph 0060; 0070; 0071; 0075
(2019/02/02)
-
- Anti-inflammatory pharmaceutical compounds containing 2,5-diaryloxazole compounds
-
The present invention efficiently diaryloxazole compounds inside the victims of the commercial starting material from 2, 5 - configurated. The synthesis [...] (Delepine) [pu [pu] l - the adventures reaction a hole of major steps reaction. In the present invention synthesized oxazole compounds the present invention with respect to the victims of the RAW 264. 7 NO generation have caused LPS - in assessing, oxazole compounds of the present invention depending on the concentration of the present invention were found to significantly NO billion number generation number may be likely oxazole compounds are anti-inflammatory compound as a lever with each other. (by machine translation)
- -
-
Paragraph 0023; 0033; 0034; 0036; 0038
(2019/02/21)
-
- 4 - Substituted benzene sulfonamide derivative and its preparation method and application
-
The present invention discloses a class of new 4-substituted benzene sulfonamide derivatives represented by a formula (I), wherein the 4-substituted benzene sulfonamide derivatives have good antitumor activity, and each group is defined in the specification. The present invention further discloses a preparation method of the derivative, a pharmaceutical composition containing the derivative, and applications of the 4-substituted benzene sulfonamide derivative and the pharmaceutical composition containing the derivative as the antitumor drug. The formula I is defined in the specification.
- -
-
Paragraph 0139; 0209-0212
(2018/04/21)
-
- Trisubstituted Pyridinylimidazoles as Potent Inhibitors of the Clinically Resistant L858R/T790M/C797S EGFR Mutant: Targeting of Both Hydrophobic Regions and the Phosphate Binding Site
-
Inhibition of the epidermal growth factor receptor represents one of the most promising strategies in the treatment of lung cancer. Acquired resistance compromises the clinical efficacy of EGFR inhibitors during long-term treatment. The recently discovered EGFR-C797S mutation causes resistance against third-generation EGFR inhibitors. Here we present a rational approach based on extending the inhibition profile of a p38 MAP kinase inhibitor toward mutant EGFR inhibition. We used a privileged scaffold with proven cellular potency as well as in vivo efficacy and low toxicity. Guided by molecular modeling, we synthesized and studied the structure-activity relationship of 40 compounds against clinically relevant EGFR mutants. We successfully improved the cellular EGFR inhibition down to the low nanomolar range with covalently binding inhibitors against a gefitinib resistant T790M mutant cell line. We identified additional noncovalent interactions, which allowed us to develop metabolically stable inhibitors with high activities against the osimertinib resistant L858R/T790M/C797S mutant.
- Günther, Marcel,Lategahn, Jonas,Juchum, Michael,D?ring, Eva,Keul, Marina,Engel, Julian,Tumbrink, Hannah L.,Rauh, Daniel,Laufer, Stefan
-
p. 5613 - 5637
(2017/07/22)
-
- Efficient Synthesis and In Vitro Biological Evaluation of 2,5-Diaryloxazoles as Potential Nitric Oxide Production Inhibitors
-
An efficient first synthesis of 2,5-diaryloxazoles 1–5 was accomplished from commercially inexpensive precursors and in overall yields of 38–48%. The synthesis proceeds via α-aminoketones and cyclodehydration (Robinson–Gabriel reaction) as key step. Next, these oxazoles were examined for their inhibitory effect against nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 cells and were found to display concentration-dependent inhibition of NO production without cytotoxicity. Of note, compound 3 (70.7%; IC50 = 2.33 μM) was identified as a potent inhibitor in view of its comparable inhibitory effect with the positive control, NG-monomethyl-L-arginine acetate (L-NMMA) (79.3%; IC50 = 4.51 μM) followed by compounds 5 (68.3%; IC50 = 2.30 μM) and 2 (53.9%; IC50 = 6.31 μM). As a whole, compound 3 may hold great promise for further development of NO production targeted anti-inflammatory agent.
- Jang, Ha Young,Damodar, Kongara,Kim, Jin-Kyung,Jun, Jong-Gab
-
p. 1481 - 1485
(2017/12/04)
-
- Efficient approach to thiazolidinones via a one-pot three-component reaction involving 2-amino-1-phenylethanone hydrochloride, aldehyde and mercaptoacetic acid
-
A highly efficient three-component reaction has been developed for the synthesis of thiazolidinones involving the reaction of 2-amino-1-phenylethanone hydrochloride with an aromatic aldehyde and mercaptoacetic acid in the presence of diisopropylethylamine in a single pot. Critically, this reaction exhibited excellent chemoselectivity, with the nitrogen atom of the 2-amino-1-phenylethanone component reacting selectively with the aromatic aldehyde to give the corresponding Schiff base. Nucleophilic attack at the carbon of the Schiff base by the sulfur atom of mercaptoacetic, followed by a cyclocondensation reaction between the nitrogen and the carboxylic acid moiety afforded the desired thiazolidinones, which were fully characterized by spectroscopic techniques.
- Chate, Asha Vasantrao,Tathe, Akash Gitaram,Nagtilak, Prajyot Jayadev,Sangle, Sunil M.,Gill, Charansingh H.
-
p. 1997 - 2002
(2016/12/09)
-
- Synthetic, enzyme kinetic, and protein crystallographic studies of C-β-D-glucopyranosyl pyrroles and imidazoles reveal and explain low nanomolar inhibition of human liver glycogen phosphorylase
-
C-β-D-Glucopyranosyl pyrrole derivatives were prepared in the reactions of pyrrole, 2-, and 3-aryl-pyrroles with O-peracetylated β-D-glucopyranosyl trichloroacetimidate, while 2-(β-D-glucopyranosyl) indole was obtained by a cross coupling of O-perbenzylated β-D-glucopyranosyl acetylene with N-tosyl-2-iodoaniline followed by spontaneous ring closure. An improved synthesis of O-perbenzoylated 2-(β-D-glucopyranosyl) imidazoles was achieved by reacting C-glucopyranosyl formimidates with α-aminoketones. The deprotected compounds were assayed with isoforms of glycogen phosphorylase (GP) to show no activity of the pyrroles against rabbit muscle GPb. The imidazoles proved to be the best known glucose derived inhibitors of not only the muscle enzymes (both a and b) but also of the pharmacologically relevant human liver GPa (Ki?=?156 and 26?nM for the 4(5)-phenyl and -(2-naphthyl) derivatives, respectively). An X-ray crystallographic study of the rmGPb-imidazole complexes revealed structural features of the strong binding, and also allowed to explain the absence of inhibition for the pyrrole derivatives.
- Kantsadi, Anastassia L.,Bokor, éva,Kun, Sándor,Stravodimos, George A.,Chatzileontiadou, Demetra S.M.,Leonidas, Demetres D.,Juhász-Tóth, éva,Szakács, Andrea,Batta, Gyula,Docsa, Tibor,Gergely, Pál,Somsák, László
-
supporting information
p. 737 - 745
(2016/08/17)
-
- Bisindolyl maleimide derivative and preparation method and application thereof
-
The invention provides a bisindolyl maleimide derivative and a preparation method and application thereof. The bisindolyl maleimide derivative has an excellent alpha-glucosidase inhibition effect and can be used for preventing and treating diabetes.
- -
-
Paragraph 0715
(2017/01/02)
-
- Bisindolylmaleimide derivative, and preparation method and use thereof
-
The invention provides a bisindolylmaleimide derivative, and a preparation method and a use thereof. The bisindolylmaleimide derivative has a good tumor treatment effect, especially has a good treatment effect on some drug-resistant tumors, and can realize accurate treatment of the drug-resistant tumors.
- -
-
Paragraph 0717; 0718
(2017/04/03)
-
- Biomimetic semi-synthesis of fradcarbazole A and its analogues
-
The first synthesis of fradcarbazole A (1) has been accomplished by using a biomimetic intramolecular cyclization/dehydration to construct the staurosporine-thiazole-indole skeleton. The phenyl and oxazole analogues of fradcarbazole A (2-4) were also synthesized using the same strategy. Compounds 1-4 displayed cytotoxicity against A549 cell line with IC50 values of 0.4-3.6 μM, induction of G0/G1 arrest of A549 cell cycle at 10 μM, and inhibition of PKC-β kinase with IC50 values of 0.5-0.9 μM.
- Wang, Liping,Mei, Xiangui,Wang, Cong,Zhu, Weiming
-
p. 7990 - 7997
(2015/12/31)
-
- AMINOPYRIDINE DERIVATIVES AS TAM FAMILY KINASE INHIBITORS
-
Provided herein are aminopyridine derivatives and pharmaceutical compositions that are useful as TAM family kinase inhibitors.
- -
-
Page/Page column 58
(2015/06/11)
-
- Discovery and synthesis of a novel series of liver X receptor antagonists
-
Fourteen novel compounds were prepared and their antagonistic activities against liver X receptors (LXR) α/β were tested in vitro. Compound 26 had an IC50 value of 6.4 μM against LXRα and an IC50 value of 5.6 μM against LXRβ. Docking studies and the results of structure-activity relationships support the further development of this chemical series as LXRα/β antagonists.
- Nian, Siyun,Gan, Xia,Tan, Xiangduan,Yu, Zhenpeng,Wang, Panfeng,Chen, Xing,Wang, Guoping
-
p. 628 - 635
(2015/09/07)
-
- PURINE DERIVATIVES FOR THE TREATMENT OF VIRAL INFECTIONS
-
The present invention relates to purine derivatives of formula (I), processes for their preparation, pharmaceutical compositions, and their use in treating viral infections.
- -
-
Page/Page column 14
(2013/05/23)
-
- Rearrangement of N-tert-butanesulfinyl α-halo imines with alkoxides to N-tert-butanesulfinyl 2-amino acetals as precursors of N-protected and N-unprotected α-amino carbonyl compounds
-
Reaction of N-tert-butanesulfinyl α-halo imines with alkoxides afforded new N-tert-butanesulfinyl 2-amino acetals in good to excellent yield. These N-tert-butanesulfinyl 2-amino acetals are convenient precursors for the TMSOTf-promoted synthesis of the co
- Colpaert, Filip,Mangelinckx, Sven,Denolf, Bram,De Kimpe, Norbert
-
experimental part
p. 6023 - 6032
(2012/10/08)
-
- CHEMICAL COMPOUNDS
-
The invention is directed to 6-(4-pyι?midinyl)-1 H-indazole derivatives. Specifically, the invention is directed to compounds according to Formula (I) wherein R1 - R4 are defined herein. The compounds of the invention are inhibitors of PDK1 and can be useful in the treatment of immune and metabolic diseases and disorders characterized by constitutively activated ACG kinases such as cancer and more specifically cancers of the breast, colon, and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PDK1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
- -
-
Page/Page column 231-232
(2010/07/10)
-
- SMALL MOLECULE INHIBITORS OF PLASMODIUM FALCIPARUM DIHYDROOROTATE DEHYDROGENASE
-
Inhibitors of dihydroorotate dehydrogenase (DHODH) for the Plasmodium enzyme have been identified and characterized. The inhibitors have high specificity, submicromolar efficacy against cultured parasite strains, exhibit drug-like properties, and are not overtly cytotoxic.
- -
-
-
- P70 S6 KINASE INHIBITORS
-
The present invention provides p70 S6 kinase inhibitors of the formula: pharmaceutical formulations comprising them, and methods for their use.
- -
-
Page/Page column 16-17
(2009/01/20)
-
- BICYCLIC PYRIMIDINONES AND USES THEREOF
-
The present invention provides a compound of Formula I or a pharmaceutically acceptable derivative, salt or prodrug thereof. Further provided is a method of treatment or prophylaxis of a viral infection in a subject comprising administering to said subject an effective amount of a compound of Formula I or a pharmaceutically acceptable derivative, salt or prodrug thereof. A pharmaceutical composition or medicament comprising a compoundof Formula I is also provided.
- -
-
Page/Page column 66-67
(2008/12/06)
-
- Synthesis and biological evaluation of imidazol-2-one derivatives as potential antitumor agents
-
A new series of aryl substituted imidazol-2-one derivatives structurally related to combretastatin A-4 (CA-4) were synthesized and evaluated for their cytotoxic activities in vitro against various human cancer cell lines including MDR cell line. The cytotoxic effects of compounds 7b and 7i proved to be similar to or greater than that of docetaxel. The highly active compound 7b also exhibited excellent inhibitory activity on tumor growth in vivo.
- Xue, Na,Yang, Xiaochun,Wu, Rui,Chen, Jing,He, Qiaojun,Yang, Bo,Lu, Xiuyang,Hu, Yongzhou
-
p. 2550 - 2557
(2008/09/21)
-
- ANTIBACTERIAL BENZOIC ACID DERIVATIVES
-
The invention provides antimicrobial agents and methods of using the agents for sterilization, sanitation, antisepsis, disinfection, and treatment of infections in mammals.
- -
-
-
- Water-binding solid scintillators: Synthesis, emission properties, and tests in 3H and 14C counting
-
Spectral and time-resolved fluorescence properties as well as relative fluorescence quantum yields of carbodiimide derivatives of 2,5-diphenyloxazole (PPO) (prepared by H2S elimination from the corresponding thioureas), of some intermediates in the preparation, and of several other PPO derivatives were investigated in solution and in the solid state to test their suitability as solid scintillators. The carbodiimides reacted slowly with water under acidic conditions to yield ureas. These systems were compared with solid mixtures of other PPO derivatives with sodium sulfate as a drying agent, as chemically water-binding solid scintillators in 3H and 14C counting. Both the chemically and the absorptive water-binding scintillators proved capable of counting 3H and 14C decay, and open a way to the counting of aqueous samples by solid scintillators without a drying step.
- Meyer, Hans-Joachim,Wolff, Thomas
-
p. 2809 - 2817
(2007/10/03)
-
- Pyrrolomorphinans as δ opioid receptor antagonists. The role of steric hindrance in conferring selectivity
-
A series of 2',3'-disubstituted pyrrolomorphinans (5a-i) were synthesized to determine the role of steric hindrance at μ and γ receptors in promoting δ opioid receptor antagonist selectivity. In smooth muscle preparations, five members of the series (5a-c,e,f) possessed K(e) values in the range 2-15 nM and were 6 selective. Since the unsubstituted analogue 4 possessed δ antagonist potency of similar magnitude, but was not δ selective, it is suggested that the 2',3'substitution confers δ selectivity by hindering the interaction of the pharmacophore at μ and γ receptors, while not affecting δ receptors.
- Farouz-Grant,Portoghese
-
p. 1977 - 1981
(2007/10/03)
-
- Process for the preparation of alpha-aminoketone salts
-
There is disclosed a process for the preparation of an alpha-aminoketone salt of formula I STR1 which comprises reacting a nitrosated keto ester of formula II STR2 with a carboxylic anhydride of formula IV STR3 under the conditions of catalytic hydrogenation, to a compound of formula III STR4 which compound of formula III is then hydrolysed with an acid Hn A to the salt I, in which formulae above R1 is C1 -C6 alkyl, phenoxy-C1 -C4 alkyl, phenyl, C7 -C9 phenylalkyl, or phenyl or C7 -C9 phenylalkyl which are substituted by halogen, C1 -C6 alkyl or C1 -C6 alkoxy, hydroxy or cyano, R2 is C1 -C4 alkyl or cyclohexyl, n is 1 to 3, R3 is C1 -C4 alkyl and A is the radical of an organic or mineral protic acid. Pyrroles suitable as co-stabilisers for PVC can be prepared from alpha-aminoketone salts of formula I.
- -
-
-
- SYNTHESIS OF LUMINOPHORIC DERIVATIVES OF PBD BASED ON 2,5-DIARYL SUBSTITUTED THIAZOLES AND OXAZOLES
-
The Friedel-Crafts acylation of 2-(biphenyl-4-yl)-5-phenyl-1,3,4-oxadiazole (PBD) with hippuryl chloride has been used to prepare the derivative V which on cyclization with POCl3 or P4S10 gives the respective oxazole (or thiazole) derivative of PBD, XIa or XIb.The reaction of carboxylic acid II with 4-(ω-aminoacetyl)biphenyl in the presence of CDI gives N-acyl-α-aminoketone VII; the analogous compound VI has been prepared by acylating ω-aminoacetophenone with acyl chloride III.The cyclization of these compounds gives bifluorophores Xa - Xd.
- Lhotak, Pavel,Kurfuerst, Antonin
-
p. 2720 - 2728
(2007/10/02)
-
- Synthesis and anticonvulsant activity of some new 4-aryl-4-imidazoline-2-one derivatives
-
In this study, some new 4-aryl-4-imidazoline-2-one deriratives have been prepared by the reaction of potassium cyanate with some aminoethanone hydrochlorides. The structure of these compounds have been confirmed by UV, IR, 1H-NMR and elementary analysis. Their anticonvulsant activities were determined by maximal electroshock (MTS) and subcutaneous metrazol (scMet) tests according to the ADD (Antiepileptic Drug Development) programme Phase I. Neurotoxicity of the compounds was evaluated by rotarod test. While 2 of the compounds showed protection against ScMet induced seizures at 30 and 300 mg/kg dose levels, 3 of the compounds showed neurotoxicity.
- Calis,Dalkara,Ertan
-
p. 592 - 594
(2007/10/02)
-
- A Convenient Synthesis of Primary Amines Using Sodium Diformylamide as A Modified Gabriel Reagent
-
Sodium diformylamide (1) was used as a convenient substitute for phthalimide in the Gabriel synthesis of primary amines.Reagent 1 undergoes smooth N-alkylation with alkyl halides or p-toluenesulfonates 2 in acetonitrile or dimethylformamide to give the corresponding N,N-diformylalkylamines 3 in good yields, except with alkylating agents which are susceptible to base-catalyzed elimination.The formyl group of 3 can be easily removed by hydrochloric acid to give the corresponding alkylamine hydrochlorides 5 or free alkylamines 4.
- Yinglin, Han,Hongwen, Hu
-
p. 122 - 124
(2007/10/02)
-
- A Convenient Synthesis of Aminomethyl Ketones (α-Amino Ketones)
-
Several N,N-diformylaminomethyl ketones 3 were prepared by treating the respective bromomethylketone 1 with sodium diformylamide in acetonitrile at room temperature.This reaction produced from N-formylaminomethyl ketones 4 when ethanol was used as the solvent.One of the formyl groups of N,N-difomylaminomethyl ketones was selectively removed by using a catalytic amount of sodium or potassium hydroxide in alcohol to the corresponding N-formylaminomethyl ketones 4.The formyl groups of both N,N-diformyl- and N-formylaminomethyl ketones could be easily removed by either5percent hydrochloric acid in ethanol or 6N hydrochloric acid to give the corresponding aminomethyl ketone hydrochlorides 5.These reactions are general and give high yield of the products.
- Yinglin, Han,Hongwen, Hu
-
p. 615 - 618
(2007/10/02)
-
- A CONVENIENT PREPARATION OF AMINOMETHYL ARYL KETONES AND THEIR DERIVATIVES
-
A convenient preparation of N-phenacyl diformamides, N-phenacyl formamides and aminomethyl aryl ketone hydrochlorides from aryl bromomethyl ketones and sodium diformylamide was described.
- Ying-lin, Han,Hong-ven, Hu
-
p. 5285 - 5286
(2007/10/02)
-
- Synthesis of 4-oxopyrrolopyrimidine-3-carboxylic acid derivatives as potential antimicrobial agents
-
A route for the synthesis of various derivatives of 4-oxopyrrolopyrimidine-3-carboxylic acid from 2-amino-3-cyano-4,5-dimethylpyrrole and 2-amino-3-cyano-4-arylpyrroles is described.
- Bayomi, Said M.,Al-Obaid, Abdul Rahman M.,Jado, Ahmad I.,Loutfy, Essam A.
-
p. 814 - 816
(2007/10/02)
-
- SYNTHESIS OF α-AMINO KETONE HYDROCHLORIDES VIA CHEMOSELECTIVE HYDROGENATION OF α-NITRO KETONES
-
Chemoselective hydrogenation of various α-nitro ketones was accomplished with 5percent Pt sulfide on carbon as a catalyst to afford α-amino ketone hydrochlorides in good yields.
- Tamura, Rui,Oda, Daihei,Kurokawa, Hiroshi
-
p. 5759 - 5762
(2007/10/02)
-
- New Anticancer Agents: Synthesis of 1,2-Dihydropyridopyrizines (1-Deaza-7,8-dihydropteridines)
-
Reaction of α-aminoacetophenone oximes (2) with ethyl 6-amino-4-chloro-5-nitropyridine-2-carbamate (1) gave ethyl 6-amino-5-nitro-4-pyridine-2-carbamate oximes (3), which were hydrolyzed under acidic conditions to give the corresponding ketones (4).Related pyridines substituted with keto side chain were prepared from 1 and 1,3-diaminopropanone oximes and by oxidation of the side-chain hydroxy group of ethyl 6-amino-4-amino>-5-nitropyridine-7-carbamates (6).Catalytic hydrogenation of the nitro group of 4 over Raney nickel in a large volume of ethanol gave the 1-deaza-7,8-dihydropteridines (7).Several of the oximes 3 were successfully hydrogenated to give 7 directly.The resulting 1-deaza-7,8-dihydropteridines showed potent cytotoxicity against cultured L1210 cells and significant anticancer activity against lymphocytic leukemia P-388 in mice.THese biological activities are attributed to the accumulation of cells at mitosis.
- Temple, Carroll,Wheeler, Glynn P.,Elliott, Robert D.,Rose, Jerry D.,Kussner, Conrad L.,et al.
-
p. 1045 - 1050
(2007/10/02)
-
