- Phosphine Sequentially Catalyzed Domino 1,6-Addition/Annulation: Access to Functionalized Chromans and Tetrahydroquinolines with an Ethynyl-Substituted All-Carbon Quaternary Center
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A novel phosphine sequentially catalyzed domino 1, 6-addition/annulation process has been developed using p-quinone methides (p-QMs) and α-substituted allenoates which generates a series of chroman and tetrahydroquinoline derivatives containing an ethynyl-substituted all-carbon quaternary center with up to 97% yield and 20:1 dr. value. In this reaction, allenoates act as C2 synthons.
- Zhu, Yannan,Wang, Dan,Huang, You
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Read Online
- Anthranilamide-based 2-phenylcyclopropane-1-carboxamides, 1,1'-biphenyl-4-carboxamides and 1,1'-biphenyl-2-carboxamides: Synthesis biological evaluation and mechanism of action
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Several anthranilamide-based 2-phenylcyclopropane-1-carboxamides 13a-f, 1,1’-biphenyl-4-carboxamides 14a-f and 1,1’-biphenyl-2-carboxamides 17a-f were obtained by a multistep procedure starting from the (1S,2S)-2-phenylcyclopropane-1-carbonyl chloride 11, the 1,1'-biphenyl-4-carbonyl chloride 12 or the 1,1'-biphenyl-2-carbonyl chloride 16 with the appropriate anthranilamide derivative 10a-f. Derivatives 13a-f, 14a-f and 17a-f showed antiproliferative activity against human leukemia K562?cells. Among these derivatives 13b, 14b and 17b exerted a particular cytotoxic effect on tumor cells. Derivative 17b showed a better antitumoral effect on K562?cells than 13b and 14b. Analyses performed to explore 17b mode of action revealed that it induced an arrest in G2/M phase of cell cycle which was consequent to DNA lesions as demonstrated by the increase in phospho-ATM and γH2AX, two known markers of DNA repair response system. The effect of 17b was also related to ROS generation, activation of JNK and induction of caspase-3 dependent apoptosis.
- Raffa, Demetrio,Plescia, Fabiana,Maggio, Benedetta,Raimondi, Maria Valeria,D'Anneo, Antonella,Lauricella, Marianna,Daidone, Giuseppe
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p. 262 - 273
(2017/04/03)
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- Copper-Catalyzed One-pot Synthesis of Pyrimidines from Amides, N,N′-dimethylformamide dimethylacetal, and Enamines
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A versatile copper catalyzed one-pot synthesis of diversely substituted pyrimidines directly from amides, N,N′-dimethylformamide dimethylacetal (DMF?DMA) and enamines has been established. The reaction involved the two C?N bonds and one C?C bond formation by formal [2+1+3] annulation approach to pyrimidines. This protocol is based on the use of readily available primary amides, DMF?DMA and enamines to install di- and tri-substituted pyrimidine structure with diverse functionality in one-pot manner, which makes this strategy to be appealing for the medicinal chemistry. (Figure presented.).
- Jalani, Hitesh B.,Cai, Wangshui,Lu, Hongjian
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supporting information
p. 2509 - 2513
(2017/07/22)
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- 6,7-dimethoxyquinazolines as potential cytotoxic agents: Synthesis and in vitro activity
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It has been reported that 6,7-dimethoxyquinazoline derivatives have cytotoxic potential independent of their a1-adrenoceptor blocking potential. Bioisosteres of 2-arylquinazolines are considered to have anti-tumor properties. In the present study, we have synthesized the 2-aryl and 2-arylmethyl derivatives of quinazolin-4(3H)-one while retaining the 6,7-dimethoxy substituents. Derivatives with n-butyl group attached to position-3 of quinazolinone nucleus were synthesized with the aim of increasing their lipophilicity. The potential of these synthesized compounds was evaluated against NCI (National Cancer Institute) 60 cell panel using the NCI disease oriented antitumor screen protocol. Based on the results of this screening we generalized that compounds having aryl groups directly attached to the quinazoline ring are less active than those which have one atom linker in between the two ring systems. Substitution of a lipophilic group like nbutyl decreases cytotoxic activity among the compounds and 4-aminoquinazolines showed better activity than 4-quinazolinones. Lipophilic groups in the aromatic ring yielded more active compounds as cytotoxic agents. Among the selected compounds, 4h and 13b were found to be potential lead compounds which could be further optimized as potential anti-neoplastic agents.
- Yadav, Mange Ram,Chauhan, Bishram Singh,Naik, Prashant,Gandhi, Hardik,Giridhar, Rajani
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p. 190 - 205
(2015/04/14)
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- Reversal of P-gp and BCRP-mediated MDR by tariquidar derivatives
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Abstract With an aim to generate non-toxic, specific and highly potent multidrug resistance (MDR) modulators, a novel series of anthranilic acid amide-substituted tariquidar derivatives were synthesized. The new compounds were evaluated for their cytotoxicity toward normal human colon fibroblasts (CCD18-Co), human gastric epithelial cell line (HFE) and primary rat liver cells, and for their ability to inhibit P-gp/BCRP-mediated drug efflux and reversal of P-gp and BCRP-mediated MDR in parental and drug-resistant cancer cell lines (LCC6 MDR1, MCF-7 FLV1000, R-HepG2, SW620-Ad300). While tariquidar is highly toxic to normal cells, the new derivatives exhibited much lower or negligible cytotoxicity. Some of the new tariquidar derivatives inhibited both P-gp and BCRP-mediated drug efflux whereas a few of them bearing a sulfonamide functional group (1, 5, and 16) are specific to P-gp. The new compounds were also found to potentiate the anticancer activity of the transporter substrate anticancer drugs in the corresponding transporter-overexpressing cell lines. The extent of resistance reversal was found to be consistent with the transporter inhibitory effect of the new derivatives. To further understand the mechanism of P-gp and BCRP inhibition, the tariquidar derivatives were found to interact with the transporters using an antibody-based UIC2 or 5D3 shift assay. Moreover, the transporters-inhibiting derivatives were found to modulate the ATPase activities of the two MDR transporters. Our data thus advocate further development of the new compounds for the circumvention of MDR.
- Li, Xu-Qin,Wang, Lin,Lei, Yan,Hu, Tao,Zhang, Fei-Long,Cho, Chi-Hin,To, Kenneth K.W.
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p. 560 - 572
(2015/07/28)
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- Synthesis, antiproliferative activity and possible mechanism of action of novel 2-acetamidobenzamides bearing the 2-phenoxy functionality
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Several new 2-(2-phenoxyacetamido)benzamides 17a-v, 21 and 22 were synthesized by stirring in pyridine the acid chlorides 16a-e and the appropriate5-R-4-R1-2-aminobenzamide 15a-e and initially evaluated in vitro for antiproliferative activity against the K562 (human chronic myelogenous leukemia) cell line. Some of synthesized compounds were evaluated for their in vitro antiproliferative activity against the full NCI tumor cell line panel derived from nine clinically isolated cancer types (leukemia, non-small cell lung, colon, CNS, melanoma, ovarian, renal, prostate and breast). The most active compounds caused an arrest of K562 cells in the G0-G1 phase of cell cycle and induction of apoptosis, which was mediated by caspase activation.
- Raffa, Demetrio,Maggio, Benedetta,Plescia, Fabiana,Cascioferro, Stella,Raimondi, Maria Valeria,Cancemi, Gabriella,D'Anneo, Antonella,Lauricella, Marianna,Cusimano, Maria Grazia,Bai, Ruoli,Hamel, Ernest,Daidone, Giuseppe
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p. 6305 - 6316
(2015/10/05)
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- PYRROLOBENZODIAZEPINE COMPOUNDS
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The invention relates to pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) of formula (I) and in particular to PBD dimers linked through the C1 position, and PBD monomers linked through the C1 position to aromatic groups, and pharmaceutically acceptable salts the
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Page/Page column 65-70; 73
(2015/11/24)
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- Synthesis of novel piperazine-linked anthranilic acids as potential small molecule kinase inhibitors
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Substituted anthranilic acid and piperazines were used as building blocks to prepare two libraries of compounds, with the aim being that they would exhibit biochemical activity as small molecule kinase inhibitors. The synthesized anthranilamidepiperazine
- Chakravorty, Santanu,Klein, Hanna F.,Hodson, Luke E.,Rabillier, Matthias,Fang, Zhizhou,Richters, Andre,Pelly, Stephen C.,Rauh, Daniel,Van Otterlo, Willem A.L.
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- Synthesis and Quantitative Structure-Activity Relationships of Selective BCRP Inhibitors
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The breast cancer resistance protein (BCRP/ABCG2) is a member of the ABC transporter superfamily. This protein has a number of physiological functions, including protection of the human body from xenobiotics. The overexpression of BCRP in certain tumor cell lines causes cross-resistance against various drugs used in chemotherapeutic treatment. In a previous work we showed that a new class of compounds derived from XR9576 (tariquidar) selectively inhibits BCRP. In this work we synthesized more members of this class, with modification on the second and third aromatic rings. The inhibitory activities against BCRP and P-gp were assayed using a Hoechst 33342 assay for BCRP and a calcein AM assay for P-gp. Finally, quantitative structure-activity relationships for both aromatic rings were established. The results obtained show the importance of the electron density on the third aromatic ring, influenced by substituents, pointing to interactions with aromatic residues of the protein binding site. In the second aromatic ring the activity of compounds is influenced by the steric volume of the substituents.
- Marighetti, Federico,Steggemann, Kerstin,Hanl, Markus,Wiese, Michael
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p. 125 - 135
(2013/02/26)
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- 2-Cinnamamido, 2-(3-phenylpropiolamido), and 2-(3-phenylpropanamido) benzamides: Synthesis, antiproliferativeactivity, and mechanism of action
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Several new benzamides 4a-q were synthesized by stirring in pyridine the acid chlorides 3a-q with the appropriate anthranilamide derivatives 2a-g. Some of the synthesized compounds were evaluated for their in vitro antiproliferative activity against a panel of 5 human cell lines (K562 human chronic myelogenous leukemia cells, MCF-7 breast cancer cells, HTC-116 and HT26 colon cancer cells and NCI H460 non-small cell lung cancer cells).
- Raffa, Demetrio,Maggio, Benedetta,Raimondi, Maria Valeria,Cusimano, Maria Grazia,Amico, Giandomenico,Carollo, Anna,Conaldi, Pier Giulio,Bai, Ruoli,Hamel, Ernest,Daidone, Giuseppe
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p. 427 - 435
(2013/10/01)
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- Cytotoxic potential of novel 6,7-dimethoxyquinazolines
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Herein, we report the synthesis and cytotoxicity of a series of substituted 6,7-dimethoxyquinazoline derivatives. The cytotoxic activity of all synthesized compounds has been evaluated against HCT116p53+/+ and HCT116p53 -/- colon cancer cells and a HEY ovarian cancer cell line naturally resistant to cisplatin. Nine of the tested compounds showed significant cytotoxicity in all cell lines at 10 μM. The most promising derivative (7c) showed IC50values of 0.7 and 1.7 μM in the two colon cancer cell lines.
- Yadav, Mange R.,Grande, Fedora,Chouhan, Bishram S.,Naik, Prashant P.,Giridhar, Rajani,Garofalo, Antonio,Neamati, Nouri
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experimental part
p. 231 - 243
(2012/03/26)
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- Cyclisation of 2-(2-aminophenyl)quinazolin-4(3H)-one reexamined: Formation of isomeric angular fused quinazolinoquinazolinones and their spectroscopic identification
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Cyclisation of 2-(2-aminophenyl)quinazolin-4(3H)-ones on to N3 and on to N1 leading to 6-alkyl-(8H)-quinazolino[4,3-b]quinazolin-8- one and 6-alkyl-(13H)-quinazolino[3,4-a]quinazolin-13-one, respectively was described for the first time. The differences in the IR and carbon NMR data of these isomeric fused quinazolinoquinazolinones afford a useful method for distinguishing between the two series.
- Venkateswarlu, Somepalli,Satyanarayana, Meka,Murthy, Gandrothu Narasimha,Siddaiah, Vidavalur
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scheme or table
p. 2643 - 2646
(2012/06/30)
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- Structure-activity relationships of monomeric C2-aryl pyrrolo[2,1- c ][1,4]benzodiazepine (PBD) antitumor agents
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A comprehensive SAR investigation of the C2-position of pyrrolo[2,1-c][1,4]benzodiazepine (PBD) monomer antitumor agents is reported, establishing the molecular requirements for optimal in vitro cytotoxicity and DNA-binding affinity. Both carbocyclic and
- Antonow, Dyeison,Kaliszczak, MacIej,Kang, Gyoung-Dong,Coffils, Marissa,Tiberghien, Arnaud C.,Cooper, Nectaroula,Barata, Teresa,Heidelberger, Sibylle,James, Colin H.,Zloh, Mire,Jenkins, Terence C.,Reszka, Anthony P.,Neidle, Stephen,Guichard, Sylvie M.,Jodrell, Duncan I.,Hartley, John A.,Howard, Philip W.,Thurston, David E.
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supporting information; experimental part
p. 2927 - 2941
(2010/09/14)
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- A new and facile synthesis of rutaecarpine alkaloids
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Relevant rutaecarpine analogues (1a-d) have been synthesized efficiently from the ring opened β-carboline derivatives (3a-d) as key intermediates. A unique one-pot reductive-cyclization as key reaction furnished the synthesis of rutaecarpine alkaloids in excellent yields. The key intermediates (3a-d) were prepared from tryptamine following acylation, Bischler-Napieralski cyclization, benzoylation, and oxidative cleavage of the exocyclic double bond. This new synthetic approach provides a facile access to rutaecarpine analogues with potent inhibitory effect on platelet aggregation.
- Lee, Chih-Shone,Liu, Cheng-Kuo,Cheng, Yen-Yao,Teng, Che-Ming
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experimental part
p. 1047 - 1056
(2009/10/04)
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- One-pot reductive-cyclization as key step for the synthesis of rutaecarpine alkaloids
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The quinazolinocarboline alkaloids including rutaecarpine (1a), euxylophoricine A (1b), and euxylophoricine C (1c) have been synthesized efficiently from the ring opened β-carboline derivative as key intermediate by a one-pot reductive-cyclization reaction. The key intermediate was prepared from tryptamine (6) following Bischler-Napieralski cyclization, benzoylation, and oxidative cleavage of the exocyclic double bond.
- Lee, Chih-Shone,Liu, Cheng-Kuo,Chiang, Yuen-Lin,Cheng, Yen-Yao
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p. 481 - 484
(2008/09/17)
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- RHO KINASE INHIBITORS
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The present invention relates to inhibitors of ROCKl and R0CK2, which may be selective for R0CK2, and methods of modulating the pharmacokinetic and/or pharmacodynamic properties of such compounds. Also provided are methods of inhibiting ROCKl and/or R0CK2. Also provided are treatments combining inhibitors of ROCKl and/or R0CK2 with statins.
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Page/Page column 153
(2008/12/05)
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- QUINAZOLINE DERIVATIVE USEFUL AS TOLL-LIKE RECEPTOR ANTAGONIST
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Compound CPG 52364 having formula (I) and pharmaceutically acceptable salts thereof are inhibitors of signaling by Toll-like receptors TLR7, TLR8, and TLR9, and they are useful in treatment of unwanted Immune activity. Pharmaceutical composition including
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Page/Page column 39-40
(2009/01/24)
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- Isotope effects in photochemistry: Application to chromatic orthogonality
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Equation Presented The main challenge in developing new wavelength-specific photolabile protecting groups is the rigorous control of the photolysis rate. This rate is controlled by two factors: the chromophore absorbance and the reaction quantum yield. Fine-tuning the properties by changing substituents or structural features is difficult, because both factors are independently affected. By the use of the kinetic isotope effect, we could tune the quantum yield without altering the absorbance, and hence control the overall reaction rate. We exemplified this approach with chromatically orthogonally protected diesters.
- Blanc, Aurelien,Bochet, Christian G.
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p. 2649 - 2651
(2008/02/08)
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- Facile synthesis of pyrrolo[2,1-c][1,4]benzodiazepine-5,11-dione dimer
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Efficient synthesis of biological important pyrrolo[2,1-c][1,4] benzodiazepine-5,11-dione dimer linked through the C-2 positions by fumarate group is described.
- Al-Said, Naim H.
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p. 1091 - 1093
(2007/10/03)
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- TOPOISOMERASE INHIBITORS AND PRODRUGS
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Compositions and methods for treating cancer and other hyperproliferatice disease conditions with topoisomerase inhibitors and their prodrugs are disclosed.
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Page/Page column 65; 66
(2008/06/13)
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- PHARMACOKINETICALLY IMPROVED COMPOUNDS
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The present invention relates to inhibitors of ROCKl and R0CK2 and methods of modulating the pharmacokinetic and/or pharmacodynamic properties of such compounds. Also provided are methods of inhibiting ROCKl and or R0CK2 that are useful for the treatment of disease.
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Page/Page column 138
(2010/11/24)
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- NOVEL P-GLYCOPROTEIN INHIBITOR, METHOD FOR THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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A p-glycoprotein inhibitor of Formula 1 is capable of effectively preventing the development of multi-drug resistance directed to an anticancer agent in cancer cells, and greatly enhances the bioavailability of the drug, such as paclitaxel, which is not readily absorbed when orally administered.
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Page/Page column 14-15
(2008/06/13)
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- SYNTHESIS OF PROTECTED PYRROLOBENZODIAZEPINES
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A method of synthesis of a N-10 protected PBD compound of formula (I) via an intermediate of formula (II) or formula (V).
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Page/Page column 39-40
(2010/02/11)
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- A novel approach to the synthesis of cytotoxic C2-C3 unsaturated pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) with conjugated acrylyl C2-substituents
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A concise synthesis of three novel C2-C3 unsaturated pyrrolo[2,1-c][1,4] benzodiazepine analogues (18-20) containing conjugated acrylyl C2-substituents is reported that utilises Heck coupling to install the C2-acrylyl side chains. These analogues possess
- Chen, Zhizhi,Gregson, Stephen J.,Howard, Philip W.,Thurston, David E.
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p. 1547 - 1549
(2007/10/03)
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- Isotope effects in photochemistry. 1. o-nitrobenzyl alcohol derivatives
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The photolysis of o-nitrobenzyl alcohol derivatives shows a strong kinetic isotope effect (KIE up to 8.3) at the benzylic center. For some derivatives, the KIE is wavelength dependent, suggesting the involvement of higher excited states. In addition to th
- Blanc, Aurelien,Bochet, Christian G.
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p. 7174 - 7175
(2007/10/03)
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- Synthesis and biological evaluation of benzamides and benzamidines: Structural requirement of a pyrimidine ring for inhibition of EGFR tyrosine kinase
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The benzamides 1 and the benzamidines 2-3 were synthesized as the mimics of 4-anilinoquinazolines, which possess inhibition of epidermal growth factor receptor (EGFR) tyrosine kinase, and tested for cytotoxicity toward A431 and inhibitory activity toward
- Asano, Toru,Yoshikawa, Tomohiro,Nakamura, Hiroyuki,Uehara, Yoshimasa,Yamamoto, Yoshinori
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p. 2299 - 2302
(2007/10/03)
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- Benzamides and benzamidines as specific inhibitors of epidermal growth factor receptor and v-Src protein tyrosine kinases
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The benzamides 1 and the benzamidines 2 as well as the cyclic benzamidines 3 were designed and synthesized as the mimics of 4-anilinoquinazolines for an inhibitor of EGFR tyrosine kinase. The specific inhibitions of EGFR tyrosine kinase were observed in the benzamides 1c and 1d, and the benzamidine 2a, whereas the specific inhibitions of v-Src kinase were observed in the benzamide 1j and the benzamidine 2d at a 10μg/mL concentration of compounds. The cyclic benzamidines 3a and 3b showed potent kinase inhibition of EGFR at a 1.0μg/mL concentration. According to the docking simulation using the X-ray structure of EGFR kinase domain in complex with erlotinib, the LigScore2 scoring function value of erlotinib was calculated as 5.61, whereas that of the benzamide 1c was 5.05. In a similar manner, the LigScore2 value of the cyclic benzamidine 3a was calculated as 5.10.
- Asano, Toru,Yoshikawa, Tomohiro,Usui, Taikou,Yamamoto, Hiroshi,Yamamoto, Yoshinori,Uehara, Yoshimasa,Nakamura, Hiroyuki
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p. 3529 - 3542
(2007/10/03)
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- Synthesis and DNA binding affinity of novel A-C8/C-C2-exo unsaturated alkoxyamido-linked pyrrolo[2,1-c][1,4]benzodiazepine dimers.
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The synthesis of novel A-C8/C-C2-exo unsaturated alkoxyamido-linked pyrrolo[2,1-c][1,4]benzodiazepine dimers is reported and these dimers show significant DNA binding affinity and they also exhibit moderate anticancer activity.
- Kamal, Ahmed,Srinivas,Ramulu,Ramesh,Kumar, P Praveen,Kumar, M Shiva
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p. 4337 - 4350
(2007/10/03)
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- Organic phenyl arsonic acid compounds with potent antileukemic activity
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A series of 12 organic arsonic acid compounds has been synthesized and evaluated against human B-lineage (NALM-6) and T-lineage (MOLT-3) acute lymphoblastic leukemia (ALL) cell lines. The lead compounds 2-trichloromethyl-4-[4′-(4″-phenylazo)phenylarsonic acid]aminoquinazoline (compound 19, PHI-P518; IC50=1.1±0.5 μM against NALM-6 and 2.0±0.8 μM against MOLT-3) and 2-methylthio-4-(2′-phenylarsonic acid)aminopyrimidine (compound 15, PHI-P381; IC50=1.5±0.3 μM against NALM-6 and 2.3±0.5 μM against MOLT-3) exhibited potent antileukemic activity at low micromolar concentrations.
- Liu, Xing-Ping,Narla, Rama Krishna,Uckun, Fatih M.
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p. 581 - 583
(2007/10/03)
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- Phenylarsonic acid compounds with broad-spectrum and potent cytotoxic activity against human cancer cells
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The in vitro cytotoxic activity profile of nine novel phenylarsonic acid (CAS 98-05-5, PAA) compounds against 17 human cancer cell lines including (a) ovarian cancer cell lines ES-2, PA-1, CAOV-3, OVCAR-3, (b) testicular cancer cell lines Ntera-2, Tera-2, N2NICP, 833K, and 64CP, (c) multiple myeloma cell lines ARH77, HS-Sultan, RPMI-8226, and U266, and (d) acute lymphoblastic leukemia (ALL) cell lines NALM-6, MOLT-3, ALL-1, and RS4; 11, was determined by the MTT assay. The lead compounds, 2-methylthio4- [(4′-aminophenylazo)-phenylarsonic acid] pyrimidine (PHI-370) and 2-methylthio-4-(4′-phenylarsonic acid)-aminopyrimidine (PHI-380) caused apoptotic death in all 17 cancer cell lines at low micromolar concentrations, as documented by TUNEL assays and confocal laser scanning microscopy. PHI-380 was also tested and found to be very active against primary tumor cells isolated from surgical biopsy specimens of 14 patients with therapy-refractory non-small cell lung cancer, breast cancer, colon cancer, lymphoma, hepatoblastoma, or Wilm's tumor as well. Because of their broad-spectrum and potent anticancer activity and ability to induce apoptosis in primary tumor cells from therapy-refractory cancer patients, PAA compounds such as PHI-370 and PHI-380 may provide the basis for effective salvage regimens for patients with recurrent cancer.
- Uckun, Fatih M.,D'Cruz, Osmond J.,Liu, Xing-Ping,Narla, Rama Krishna
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p. 428 - 439
(2007/10/03)
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- Synthesis and structure-activity relationship of diarylamide urea derivatives as selective inhibitors of the proliferation of human coronary artery smooth muscle cells.
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A series of diarylamide urea derivatives were synthesized and evaluated for their inhibitory activities against human coronary artery smooth muscle cells (SMCs) and human coronary artery endothelial cells (ECs). Compound 2o was superior to the lead compound, Tranilast, in terms of its potency of the inhibitory activity and cell selectivity.
- Ogita, Haruhisa,Isobe, Yoshiaki,Takaku, Haruo,Sekine, Rena,Goto, Yuso,Misawa, Satoru,Hayashi, Hideya
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p. 1865 - 1871
(2007/10/03)
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- 6,7-Dimethoxyquinazolines and therapeutic use thereof
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Quinazoline compounds and methods for the treatment of cancer and for the treatment of allergic reactions.
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- Pyrrolobenzodiazepines
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Compounds of the formulae Ia and Ib: wherein:A is CH2, or a single bond;R2 is selected from: R, OH, OR, CO2H, CO2R, COH, COR, SO2R, CN;R6, R7 and R9 are independently selected from H, R, OH, OR, halo, amino, NHR, nitro, Me3Sn;and R8 is selected from H, R, OH, OR, halo, amino, NHR, nitro, Me3Sn, where R is as defined above, or the compound is a dimer with each monomer being the same or different and being of formula Ia or Ib, where the R8 groups of the monomers form together a bridge having the formula -X-R'-X- linking the monomers, where R' is an alkylene chain containing from 3 to 12 carbon atoms, which chain may be interrupted by one or more hetero-atoms and/or aromatic rings and may contain one or more carbon-carbon double or triple bonds, and each X is independently selected from O, S, or N; except that in a compound of formula Ia when A is a single bond, then R2 is not CH=CH(CONH2) or CH=CH(CONMe2). Other related compounds are also disclosed.
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Page 32, 40, 104, 106
(2010/11/29)
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- Effect of C2-exo unsaturation on the cytotoxicity and DNA-binding reactivity of pyrrolo[2,1-c][1,4]benzodiazepines
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A series of novel C2-exo unsaturated pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) has been synthesised via a versatile pro-C2 ketone precursor. C2-exo-unsaturation enhances both DNA-binding reactivity and in vitro cytotoxic potency. (C) 2000 Elsevier Science Ltd. All rights reserved.
- Gregson, Stephen J.,Howard, Philip W.,Corcoran, Kathryn E.,Barcella, Simona,Yasin, Maqsood M.,Hurst, Abigail A.,Jenkins, Terence C.,Kelland, Lloyd R.,Thurston, David E.
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p. 1845 - 1847
(2007/10/03)
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- 6-alkylamino- and 2,3-dihydro-3′-methoxy-2-phenyl-4-quinazolinones and related compounds: Their synthesis, cytotoxicity, and inhibition of tubulin polymerization
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As part of our continuing search for potential anticancer candidates among 2-phenyl-4-quinolones and 2-phenyl-4-quinazolinones, two series of 6,7,2′,3′,4′,5′-substituted 2-phenyl-4-quinazolinones and 6,2′,3′,4′,5′-substituted 2,3-dihydro-2-phenyl-4-quinazolinones were synthesized and evaluated for cytotoxicity and as inhibitors of tubulin polymerization. In general, a good correlation was found between the two activities. Five of the 6-substituted heterocyclic 2-phenyl-4-quinozolinones (37-51) showed significant cytotoxicity against a panel of human tumor cell lines with EC50 values in the low micromolar to nanomolar concentration ranges. Compound 38 was the most potent of these compounds, as well as the most potent inhibitor of tubulin polymerization in this series. The activity of 38 was in the same range as those of the antimitotic natural products, colchicine, podophyllotoxin, and combretastatin A-4. Substituted 2-phenyl-4-quinazolinones and 2,3-dihydro-2-phenyl-4-quinazolinones also displayed highly selective cytotoxicity against the ovarian cancer 1A9 and P-gp resistant KB-VIN cell lines.
- Hour,Huang,Kuo,Xia,Bastow,Nakanishi,Hamel,Lee
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p. 4479 - 4487
(2007/10/03)
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- ORTHO-ANTHRANILAMIDE DERIVATIVES AS ANTI-COAGULANTS
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This invention is directed to compounds of formula (III): STR1 wherein B, C, D, E, R 1, R 2 and R 3 are disclosed herein. These compounds are disclosed as being useful as anti-coagulants.
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