- Transition Metal-Free Regioselective Remote C?H Bond 2,2,2-Trifluoroethoxylation of 8-Aminoquinoline Derivatives at the C5 Position
-
The regioselective 2,2,2-trifluoroethoxylation at the C5 position of amides derived from the 8-aminoquinoline has been developed. In the presence of PIDA, an unprecedented and undirected transition metal-free transformation was achieved using the readily available and appealing 2,2,2-trifluoroethanol as the fluorinated source. The selective distal 2,2,2-trifluoroethoxylation of an array of amides was achieved in moderate to good yields (12 examples, up to 61 % yield). This approach provided efficient access to high-value added fluorinated quinoline derivatives, key building blocks for bulk and fine chemical industry.
- Ruyet, Louise,Poisson, Thomas,Besset, Tatiana
-
supporting information
p. 3407 - 3410
(2021/06/28)
-
- COMPOSITIONS AND METHODS RELATED TO MOLECULAR CONJUGATION
-
The invention relates to activated Michael acceptor (AMA) compounds that can undergo conjugation with biomolecules containing Michael donor moieties, thereby providing plasma-stable antibody-drug conjugates (ADCs). Pharmaceutical compositions of the ADCs are disclosed as well. Also provided herein are a number of applications (e.g., therapeutic applications) in which the compositions are useful.
- -
-
-
- FUSED HETEROCYCLIC BENZODIAZEPINE DERIVATIVES AND USES THEREOF
-
The present disclosure provides compounds and compositions capable of extending lifespan, and methods of use thereof.
- -
-
-
- Structure–activity relationship study of novel quinazoline-based 1,6-naphthyridinones as MET inhibitors with potent antitumor efficacy
-
As a privileged scaffold, the quinazoline ring is widely used in the development of EGFR inhibitors, while few quinazoline-based MET inhibitors are reported. In our ongoing efforts to develop new MET-targeted anticancer drug candidates, a series of quinaz
- Zhuo, Lin-Sheng,Wu, Feng-Xu,Wang, Ming-Shu,Xu, Hong-Chuang,Yang, Fan-Peng,Tian, Yan-Guang,Zhao, Xing-E.,Ming, Zhi-Hui,Zhu, Xiao-Lei,Hao, Ge-Fei,Huang, Wei
-
-
- Heterocyclic compound, preparation method and application thereof
-
The invention relates to a heterocyclic compound in the technical field of medicines. The compound is represented by a structural general formula I or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5, R6, X, Y, Z, Cy1, Cy2, m, n and t have the meanings given in the specification; in addition, the invention also discloses an application of the compound and the pharmaceuticallyacceptable salt thereof in preparation of drugs for treating diseases caused by abnormal high expression of tyrosine kinase, especially application in preparation of drugs for treating and preventingcancers.
- -
-
Paragraph 0276-0278
(2020/07/02)
-
- Discovery of an Orally Bioavailable and Central Nervous System (CNS) Penetrant mGlu7 Negative Allosteric Modulator (NAM) in Vivo Tool Compound: N-(2-(1 H-1,2,4-triazol-1-yl)-5-(trifluoromethoxy)phenyl)-4-(cyclopropylmethoxy)-3-methoxybenzamide (VU6012962)
-
Herein, we report the discovery of a new, orally bioavailable and CNS-penetrant metabotropic glutamate receptor 7 (mGlu7) negative allosteric modulator (NAM) that achieves exposure in cerebral spinal fluid (CSF) 2.5× above the in vitro IC50 at minimum effective doses (MEDs) of 3 mg/kg in preclinical anxiety models.
- Reed, Carson W.,Yohn, Samantha E.,Washecheck, Jordan P.,Roenfanz, Hanna F.,Quitalig, Marc C.,Luscombe, Vincent B.,Jenkins, Matthew T.,Rodriguez, Alice L.,Engers, Darren W.,Blobaum, Anna L.,Conn, P. Jeffrey,Niswender, Colleen M.,Lindsley, Craig W.
-
supporting information
p. 1690 - 1695
(2019/02/24)
-
- NOVEL BENZODIAZEPINE DERIVATIVES AND USES THEREOF
-
The present disclosure provides compounds and compositions capable of extending lifespan, and methods of use thereof.
- -
-
-
- METHODS OF PREPARING INDOLINOBENZODIAZEPINE DERIVATIVES
-
The invention provides novel methods for preparing indolinobenzodiazepine monomer compounds and their synthetic precursors.
- -
-
Page/Page column 26
(2018/11/22)
-
- Design and discovery of 4-anilinoquinazoline-urea derivatives as dual TK inhibitors of EGFR and VEGFR-2
-
EGFR and VEGFR-2 are involved in pathological disorders and the progression of different kinds of tumors, the combined blockade of EGFR and VEGFR signaling pathways appears to be an attractive approach to cancer therapy. In this work, a series of 4-anilinoquinazoline derivatives containing substituted diaryl urea or glycine methyl ester moiety were designed and identified as EGFR and VEGFR-2 dual inhibitors. Compounds 19i, 19j and 19l exhibited the most potent inhibitory activities against EGFR (IC50?=?1?nM, 78?nM and 51?nM, respectively) and VEGFR-2 (IC50?=?79?nM, 14?nM and 14?nM, respectively), they showed good antiproliferative activities as well. Molecular docking established the interaction of 19i with the DFG-out conformation of VEGFR-2, suggesting that they might be type II kinase inhibitors.
- Zhang, Hai-Qi,Gong, Fei-Hu,Ye, Ji-Qing,Zhang, Chi,Yue, Xiao-Hong,Li, Chuan-Gui,Xu, Yun-Gen,Sun, Li-Ping
-
p. 245 - 254
(2016/10/03)
-
- Histone lysine methyltransferase structure activity relationships that allow for segregation of G9a inhibition and anti-Plasmodium activity
-
Plasmodium falciparum HKMTs (PfHKMTs) play a key role in controlling Plasmodium gene expression and represent exciting new anti-malarial epigenetic targets. Using an inhibitor series derived from the diaminoquinazoline HKMT inhibitory chemotype, we have previously identified compounds with highly promising antimalarial activity, including irreversible asexual cycle blood stage-independent cytotoxic activity at nM concentrations, oral efficacy in in vivo models of disease, and the unprecedented ability to reactivate dormant liver stage parasites (hypnozoites). However, future development of this series will need to address host versus parasite selectivity, where inhibitory activity against human G9a is removed from the lead compounds, while maintaining potent anti-Plasmodium activity. Herein, we report an extensive study of the SAR of this series against both G9a and P. falciparum. We have identified key SAR features which demonstrate that high parasite vs. G9a selectivity can be achieved by selecting appropriate substituents at position 2, 4 and 7 of the quinazoline ring. We have also, in turn, discovered that potent G9a inhibitors can be identified by employing a 6-carbon 'Nle mimic' at position 7. Together, this data suggests that while broadly similar, the G9a and potential PfHKMT target(s) binding pockets and/or binding modes of the diaminoquinazoline analogues exhibit clear and exploitable differences. Based on this, we believe this scaffold to have clear potential for development into a novel anti-malarial therapeutic.
- Sundriyal, Sandeep,Chen, Patty B.,Lubin, Alexandra S.,Lueg, Gregor A.,Li, Fengling,White, Andrew J. P.,Malmquist, Nicholas A.,Vedadi, Masoud,Scherf, Artur,Fuchter, Matthew J.
-
supporting information
p. 1069 - 1092
(2017/07/12)
-
- PYRROLOBENZODIAZEPINE ANTIBODY DRUG CONJUGATES AND METHODS OF USE
-
The invention provides antibody-drug conjugates comprising an antibody conjugated to a pyrrolobenzodiazepine drug moiety via a disulfide linker, pyrrolobenzodiazepine linker-drug intermediates, and methods of using the antibody-drug conjugates.
- -
-
Paragraph 0571; 0572
(2017/04/23)
-
- Epidermal growth factor receptor tyrosine kinase inhibitors MPGF and MPGH with anti-tumor activity and preparation method and application thereof
-
The invention discloses epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI) MPGF and MPGH with the anti-tumor activity and a preparation method and application thereof. By optimizing and improving the chemical structure of PD153035, brand-new EGFR TKIs are obtained and named as MPGF (shown in the formula I) and MPGH (shown in the formula II). Research shows that the synthesized EGFR TKI-MPGF and EGFR TKI-MPGH can effectively inhibit tumor cell proliferation and has a stronger proliferation inhibition effect on mutational EGFR lung cancer cell line PC-9 compared with the PD153035, and therefore the EGFR TKI-MPGF and the EGFR TKI-MPGH can serve as anti-tumor agents to be applied in clinic. In addition, the invention discloses the method for preparing the epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI) MPGF and MPGH with the anti-tumor activity. By means of the epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI) MPGF and MPGH with the anti-tumor activity and the preparation method and application thereof, an effective technological means is provided for tumor treatment, especially for treatment of the non-small cell lung cancer.
- -
-
Paragraph 0044; 0045
(2016/10/27)
-
- 4-substituted anilinoquinazoline derivatives, and preparation method and application thereof
-
The invention discloses novel 4-substituted anilinoquinazoline derivatives or pharmaceutically acceptable salts thereof, or polymorphic substances, solvates or stereomers of the 4-substituted anilinoquinazoline derivatives, and a preparation method and application thereof. The 4-substituted anilinoquinazoline compounds have favorable inhibition activities for EGFR and VEGFR-2 in a biological test and have obvious effects in an in-vitro anti-human tumor cell proliferation activity test.
- -
-
Paragraph 0054; 0055
(2017/01/31)
-
- Identification and Structure–Activity Relationship Studies of Small-Molecule Inhibitors of the Methyllysine Reader Protein Spindlin1
-
The methyllysine reader protein Spindlin1 has been implicated in the tumorigenesis of several types of cancer and may be an attractive novel therapeutic target. Small-molecule inhibitors of Spindlin1 should be valuable as chemical probes as well as potential new therapeutics. We applied an iterative virtual screening campaign, encompassing structure- and ligand-based approaches, to identify potential Spindlin1 inhibitors from databases of commercially available compounds. Our in silico studies coupled with in vitro testing were successful in identifying novel Spindlin1 inhibitors. Several 4-aminoquinazoline and quinazolinethione derivatives were among the active hit compounds, which indicated that these scaffolds represent promising lead structures for the development of Spindlin1 inhibitors. Subsequent lead optimization studies were hence carried out, and numerous derivatives of both lead scaffolds were synthesized. This resulted in the discovery of novel inhibitors of Spindlin1 and helped explore the structure–activity relationships of these inhibitor series.
- Robaa, Dina,Wagner, Tobias,Luise, Chiara,Carlino, Luca,McMillan, Joel,Flaig, Ralf,Schüle, Roland,Jung, Manfred,Sippl, Wolfgang
-
supporting information
p. 2327 - 2338
(2016/10/24)
-
- Benzoic hydroxamate-based iron complexes as model compounds for humic substances: Synthesis, characterization and algal growth experiments
-
A series of monomeric and dimeric FeIII complexes bearing benzoic hydroxamates as O,O-chelates has been prepared and characterized by elemental analysis, IR spectroscopy, UV-Vis spectroscopy, electrospray ionization mass spectrometry (ESI-MS), cyclic voltammetry, EPR spectroscopy and for some examples by X-ray diffraction analysis. The stability of the synthesized complexes in pure water and seawater was monitored over 24 h by means of UV-Vis spectrometry. The ability to release iron from the synthesized model complexes has been investigated with algae growth experiments.
- Orlowska, Ewelina,Roller, Alexander,Wiesinger, Hubert,Pignitter, Marc,Jirsa, Franz,Krachler, Regina,Kandioller, Wolfgang,Keppler, Bernhard K.
-
p. 40238 - 40249
(2016/05/24)
-
- Synthesis, characterization and crystal structure of methyl 4-(benzyloxy)-5-methoxy-2-nitrobenzoate
-
Methyl 4-(benzyloxy)-5-methoxy-2-nitrobenzoate was synthesized from 4-hydroxy-3-methoxybenzoic acid. Firstly, 4-hydroxy-3-methoxybenzoic acid reacted with methanol in the presence of concentrated sulfuric acid at reflux temperature, then the product of the first step was transformed into benzyl bromide by the process of substitution reaction by using K2CO3. Finally, the product was obtained by nitration reaction with HNO3. The product was characterized by 1H NMR and LC-MS. The crystal structure of compound I was investigated using X-ray diffraction and SHELXTL-97 software. The results indicated that compound I crystallized in the monoclinic system, space group P2(1)/c with a = 5.590(2), b = 17.591 (7), c = 15.427(6) ?, V = 1516.9 (10) ?3; Z 4.
- Wang, Kai,Zhang, Xiu-Qin,Zhu, Jian,Chen, Qiang,Zhang, Zhong-Qiang,Fan, Li
-
p. 2647 - 2650
(2015/12/12)
-
- THERAPEUTIC COMPOUNDS AND USES THEREOF
-
Described herein are compounds of Formula (I) or Formula (VI), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Also provided are particles (e.g., nanoparticles) comprising compounds of Formula (I) or Formula (VI) and pharmaceutical compositions thereof that are mucus penetrating. Methods of using the compounds or pharmaceutical compositions thereof for treating diseases are also provided.
- -
-
Paragraph 0390; 0391
(2014/09/03)
-
- Identification of novel 4-anilinoquinazoline derivatives as potent EGFR inhibitors both under normoxia and hypoxia
-
A novel series of 4-anilinoquinazoline derivatives (19a-19t) were designed and synthesized through incorporation of the 2-nitroimidazole moiety into the 4-anilinoquinazoline scaffold of EGFR inhibitors. The most promising compound 19h displayed potent EGF
- Cheng, Weiyan,Yuan, Youting,Qiu, Ni,Peng, Peng,Sheng, Rong,Hu, Yongzhou
-
p. 6796 - 6805
(2015/01/08)
-
- Mechanism of drug resistance of hemagglutinin of influenza virus and potent scaffolds inhibiting its function
-
Highly pathogenic influenza viruses have become a global threat to humans. It is important to select an effective therapeutic option suitable for the subtypes in an epidemic or pandemic. To increase the options, the development of novel antiviral agents acting on targets different from those of the currently approved drugs is required. In this study, we performed molecular dynamics simulations on a spike protein on the viral envelop, hemagglutinin, for the wild-type and three kinds of mutants using a model system consisting of a trimeric hemagglutinin complex, viral lipid membrane, solvation waters, and ions. A natural product, stachyflin, which shows a high level of antiviral activity specific to some subtypes of influenza viruses, was examined on binding to the wild-type hemagglutinin by docking simulation. The compound potency of stachyflin is, however, easily lost due to resistant mutations. From a comparison of simulation results between the wild-type and the resistant mutants, the reason for the drug resistance of hemagglutinin was clarified. Next, 8 compounds were selected from a chemical database by in silico screening, considering the findings from the simulations. Inhibitory activities to suppress the proliferation of influenza virus were measured by cell-based antiviral assays, and two chemical scaffolds were found to be potent for an inhibitor. More than 30 derivatives bearing either of these two chemical scaffolds were synthesized, and cell culture assays were carried out to evaluate the compound potency. Several derivatives displayed a high compound potency, and 50% effective concentrations of two synthesized compounds were below 1 μM.
- Yanagita, Hiroshi,Yamamoto, Norio,Fuji, Hideyoshi,Liu, Xinli,Ogata, Masakazu,Yokota, Mizuho,Takaku, Hiroshi,Hasegawa, Hideki,Odagiri, Takato,Tashiro, Masato,Hoshino, Tyuji
-
scheme or table
p. 552 - 562
(2012/06/04)
-
- Synthesis of 6- and 7-propargyloxy derivatives of 4-(3-fluoroanilino)- quinazoline
-
The preparation of the novel isomeric 6- and 7-propargyloxy derivatives of 4-(3-fluoroanilino)-quinazoline was achieved using a six-step process. An alternate method to the 7-propargyloxy derivative and analogous 7-propargyloxy containing compounds is als
- Pham, Helen Trinh,Hanson, Robert N.,Olmsted, Sandra L.,Kozhushnyan, Anton,Visentin, Adam,Weglinsky, Paul J.,Massero, Chris,Bailey, Kristen
-
supporting information; scheme or table
p. 1053 - 1056
(2011/03/22)
-
- A simple route toward new clomiphene metabolites
-
A new clomiphene metabolite, extremely useful for doping analysis, was synthesized in 19% overall yield. The approach involved a Grignard reaction via a N-acylbenzotriazole intermediate to afford a key aromatic ketone and a HWE reaction. Both stereo-isomers were separated and identified. Georg Thieme Verlag Stuttgart ? New York.
- Vitoriano, Bruno C.,Carvalho, Luísa C. R.,Estev?o, Mónica S.,Sekera, Michael H.,Marques, M. Manuel B.
-
supporting information; experimental part
p. 753 - 756
(2010/06/13)
-
- STEROIDAL ANTI-HORMONE HYBRIDS
-
Disclosed are novel compounds and compositions for inhibition of androgen and estrogen receptor signaling, methods for inhibiting androgen signaling, methods for inhibiting estrogen signaling, methods for inhibiting the interaction between a co-regulatory protein and an androgen or estrogen receptor, and methods for treating cancer.
- -
-
Page/Page column 53
(2010/08/08)
-
- Substituted 2-arylbenzothiazoles as kinase inhibitors: Hit-to-lead optimization
-
Based on an (aminoaryl)benzothiazole quinazoline hit structure for kinase inhibition, a systematic optimization program resulted in a lead structure allowing for inhibitory activities in cellular phosphorylation assays in the low nanomolar range.
- Tasler, Stefan,Mueller, Oliver,Wieber, Tanja,Herz, Thomas,Pegoraro, Stefano,Saeb, Wael,Lang, Martin,Krauss, Rolf,Totzke, Frank,Zirrgiebel, Ute,Ehlert, Jan E.,Kubbutat, Michael H.G.,Schaechtele, Christoph
-
supporting information; experimental part
p. 6728 - 6737
(2009/12/09)
-
- VEGFR INHIBITORS CONTAINING A ZINC BINDING MOIETY
-
The present invention relates to VEGFR inhibitors and their use in the treatment of cell proliferative diseases such as cancer. The said derivatives may further act as HDAC inhibitors.
- -
-
Page/Page column 26
(2009/04/24)
-
- BENZO[C][2,7]NAPHTHYRIDINE DERIVATIVES, AND THEIR USE AS KINASE INHIBITORS
-
The present invention relates to Benzo[c] [2,7] naph thy ri dine Derivatives of formula (I), compositions comprising an effective amount of a Benzo[c] [2,7]naphthyridine Derivative, methods for treating or preventing a proliferative disorder or an autoimmune disease, comprising administering to a subject in need thereof an effective amount of a Benzo[c] [2,7]naphthyridine Derivative, methods for modulating PDK-I activity, PKA activity, Akt activity, S6K activity, or PKC activity, comprising administering to a subject in need thereof an effective amount of a Benzo[c] [2,7] naphthyridine Derivative. The invention also relates to processes for preparing a Benzo[c] [2,7] naphthyridine Derivative.
- -
-
Page/Page column 214
(2008/12/08)
-
- Methods of synthesizing radiolabeled 3-cyano[14C]quinolines
-
The present invention is directed to radiolabeled 3-cyanoquinolines of the formula: and methods of synthesizing the same, wherein G1, G2 R1, R4, Z, X, and n are as defined herein. The present invention is also directed to a radiolabeled intermediate compounds of formula (VII): wherein PG, G1, R1, R4, R10, and R11 are as defined herein, and synthesis of the same.
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Page/Page column 14
(2010/11/28)
-
- 2-arylbenzothiazole analogues and uses thereof
-
The present invention relates to compounds of the general formula (I) and salts, prodrugs, and stereoisomers thereof, wherein Y independently represents S, O, NR2, SO, SO2; A independently represents a fife- or six-membered aromatic carbocycle or heterocycle and wherein R1 to R20 in formula (I) represent independently of each other a variety of different substituents comprising alkyl, aryl, aralkyl, alkylaryl, heteroaryl groups and monofunctional moieties.
- -
-
Page/Page column 14
(2008/06/13)
-
- Thiazole analogues and uses thereof
-
The present invention relates to compounds of the general formula (I) and salts and physiologically functional derivatives thereof, R2 is attached at the 4- or 5-position of the thiazole ring and is hydrogen, alkyl, halogen, cyano, alkoxy, haloalkyloxy, or alkylamino; X independently represents a divalent linkage group selected from S, O, NR4, SO, or SO2; R4 is hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, or heterocyclyl; is attached at the 4- or 5-position of the thiazole ring and independently represents one of the following groups of the general formula (II): wherein the dotted line represents a single or double bond; * indicates the point of attachment to the thiazole ring; n is 1,2, or 3.
- -
-
Page/Page column 18
(2008/06/13)
-
- 2-Arylbenzothiazole analogues and uses thereof in the treatment of cancer
-
The present invention relates to anticancer compounds of the general formula (I) and salts and physiologically functional derivatives thereof, wherein Y independently represents S, O, NR 2 , SO, SO 2 ; A independently represents a five- or six-membered aromatic carbocycle or heterocycle and wherein R 1 in formula (I) represents one of the heteroaryl groups defined in the claims.
- -
-
Page/Page column 23
(2010/11/25)
-
- Thiazole Analogues and Uses Thereof
-
Compounds of formula (I) and salts and physiologically functional derivatives thereof, wherein R2 is attached at the 4- or 5-position of the thiazole ring and is hydrogen, alkyl, halogen, cyano, alkoxy, haloalkoxy, or alkylamino; X independently represents a divalent linkage group selected from S, O, NR4, SO, or SO2; R4 is hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, or heterocyclyl; R1 is attached at the 4- or 5-position of the thiazole ring and independently represents a group of formula (II): ?wherein the dotted line represents a single or double bond; * indicates the point of attachment to the thiazole ring; and n is 1, 2, or 3. Also disclosed are pharmaceutical compositions comprising the above compounds and method of treatments for cancer and other diseases.
- -
-
Page/Page column 13
(2008/06/13)
-
- 2,5- and 2,6-disubstituted benzazole analogues useful as protein kinase inhibitors
-
The present invention relates to compounds of the general formulas (I), (Ia) and (II) and salts and physiologically functional derivatives thereof, wherein the substituents -Y are attached to the 5- or 6- position of the benzazole. These compounds are useful as protein kinase inhibitors in the treatment of i.a. cancer.
- -
-
Page/Page column 26
(2008/06/13)
-
- 2,5- and 2,6-disubstituted benzazole derivatives useful as protein kinase inhibitors
-
The present invention relates to compounds of the general formula (I) and salts and physiologically functional derivatives thereof, wherein the substituent is attached to the 5- or 6- position of the benzazole; Xindependently represents S, O, SO, SO2;Yindependently represents S, O, NR2, SO, SO2;Aindependently represents ←CO-, ←CS-, ←SO-, ←SO2-, ←CO2-, ←CONR8-, ←NR8CO-, ←NR8CONR9-, ←NR8COO-, ←NR8NR9CO-, ←NR8OCO-, ←ONR8CO-, ←NR8SO2-, where ← indicates the point of attachment to R3; and wherein R1 to R19 in formula (I) represent independently of each other a variety of different substituents comprising alkyl, aryl, aralkyl, alkylaryl, heteroaryl groups and monofunctional moieties. These compounds are useful as protein kinase inhibitors in the treatment of i.a. cancer.
- -
-
Page/Page column 26
(2008/06/13)
-
- Benzazole analogues and uses thereof
-
The present invention relates to compounds of the general formulas (I), (Ia) and (II) and salts and physiologically functional derivatives thereof, wherein the substituents —Y are attached to the 5- or 6-position of the benzazole.
- -
-
Page/Page column 16
(2008/06/13)
-
- Benzazole analogues and uses thereof
-
The present invention relates to N2-heteroaryl-benzazole-2,(5 or 6)-diamine derivatives and compositions thereof as protein kinase inhibitors for the treatment of e.g. cancer.
- -
-
Page/Page column 23
(2008/06/13)
-
- QUINOLINE AND QUINOXALINE DERIVATIVES AS INHIBITORS OF KINASE ENZYMATIC ACTIVITY
-
Compounds of formula (IA) or (IB), are inhibitors of aurora kinase activity: Formula (IA), (IB) wherein -L1Y1-[CH2]z- is a linker radical wherein Y1, L1 and z are as defined in the claims; R6 is C1-C4alkoxy, hydrogen or halo; W represents a bond, -CH2-, -O-, -S-, -S(=O)2-, or -NR5- where R5 is hydrogen or C1-C4 alkyl; Q is =N-, =CH- or =C(X1)- wherein X1 is cyano, cyclopropyl or halo; linker radicals L2 are as defined in the claims; R is a radical of formula (X) or (Y): wherein R1 is a carboxylic acid group (-COOH), or an ester group which is hydrolysable by one or more intracellular carboxylesterase enzymes to a carboxylic acid group; R4 is hydrogen; or optionally substituted C1-C6 alkyl, C3-C7 cycloalkyl, aryl, aryl(C1-C6 alkyl)-, heteroaryl, heteroaryl(C1-C6 alkyl)-, -(C=O)R3, -(C=O)OR3, or -(C=O)NR3 wherein R3 is hydrogen or optionally substituted (C1-C6)alkyl, C3-C7 cycloalkyl, aryl, aryl(C1-C6 alkyl)-, heteroaryl, or heteroaryl(C1-C6 alkyl)-; R41 is hydrogen or optionally substituted C1-C6 alkyl; and D is a monocyclic heterocyclic ring of 5 or 6 ring atoms.
- -
-
Page/Page column 63-65
(2008/06/13)
-
- SUBSTITUTED N-ARYL BENZAMIDES AND RELATED COMPOUNDS FOR TREATMENT OF AMYLOID DISEASES AND SYNUCLEINOPATHIES
-
Substituted diaryl compounds of the Formulae (I, II, III), where the variables are as defined in the claims, and their pharmaceutically acceptable derivatives, their synthesis, pharmaceutical compositions containing them, and their use in the treatment of amyloid diseases, including A? amyloidosis, such as observed in Alzheimer's disease, IAPP amyloidosis, such as observed in type 2 diabetes, and synucleinopathies, such as observed in Parkinson's disease, and the manufacture of medicaments for such treatment are provided.
- -
-
Page/Page column 93
(2008/06/13)
-
- Design, synthesis, and evaluation of mixed imine-amine pyrrolobenzodiazepine dimers with efficient DNA binding affinity and potent cytotoxicity
-
Synthesis of mixed imine-amine pyrrolobenzodiazepine (PBD) dimers that are comprised of DC-81 and secondary amine (N10) of DC-81 subunits tethered to their C8 positions through alkanedioxy linkers (comprised of three and five carbons) is described. These
- Kamal, Ahmed,Ramesh,Srinivas,Ramulu,Laxman,Rehana, Tasneem,Deepak,Achary,Nagarajaram
-
p. 5427 - 5436
(2007/10/03)
-
- 2-FURANCARBOXYLIC ACID HYDRAZIDES AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME
-
The present invention provides 2-furancarboxylic acid hydrazide compounds represented by General Formula(I) below, and prodrugs, physiologically acceptable salts, hydrates, solvates thereof, methods for producing them and pharmaceutical compositions containing them: wherein A is a group represented by Formula (a) or the like: (wherein either R4 or R5 represents cyano, nitro or the like, and the other represents a hydrogen atom or the like); either R1 or R2 represents a group: -D-(X)m-R6 or the like, and the other represents a group: -E-(Y)n-R7, hydrogen atom, aryl or the like; R3 is a hydrogen atom or the like; D and E independently represent aryl; X and Y independently represent 0 or the like; R6 and R7 independently represent alkyl, aryl, arylalkyl or the like; and m and n are independently 0 or 1, provided that the aryl is optionally substituted. Such compounds exhibit a potent antagonistic activity on glucagon receptor and are of use as preventive and/or therapeutic agents for symptoms and diseases in which glucagon is involved.
- -
-
-
- Substituted 4-anilino-7-phenyl-3-quinolinecarbonitriles as Src kinase inhibitors
-
A series of substituted 4-anilino-7-phenyl-3-quinolinecarbonitriles has been prepared as Src kinase inhibitors. Optimal activity is observed with compounds that have basic amines attached via the para position of the 7-phenyl ring, and a hydrogen atom at the C-6 position. The best compounds are low nanomolar inhibitors of Src kinase, and have potent activity against Src-transformed fibroblast cells.
- Berger, Dan,Dutia, Minu,Powell, Dennis,Wissner, Allan,DeMorin, Frenel,Raifeld, Yuri,Weber, Jennifer,Boschelli, Frank
-
p. 2989 - 2992
(2007/10/03)
-
- A novel route to pyrrolo[2,1-c][1,4]benzodiazepin-5-ones. Formal total synthesis of (±)-DC-81
-
(formula presented) Compounds 3a and 3b were synthesized from N-allylisatoic anhydrides 5a and 5b in six and seven steps, respectively. Synthesis of 3b constitutes a formal total synthesis of (±)-DC-81.
- Wang, Tiansheng,Lui, Alfred S.,Cloudsdale, Ian S.
-
p. 1835 - 1837
(2008/02/11)
-
