- PYRROLOBENZODIAZEPINE DIMER PRECURSOR AND LIGAND-LINKER CONJUGATE COMPOUND THEREOF
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The present invention relates to a pyrrolobenzodiazepine dimer prodrug and a ligand-linker conjugate compound thereof, a composition containing these, and therapeutic use thereof particularly as an anticancer drug. The stability of the compounds themselves and the stability thereof in plasma are excellent and the compounds are advantageous in terms of manifestation of toxicity, and thus the compounds are industrially useful in that it is possible to target proliferative diseases such as cancer, to perform a specific treatment, to maximize the drug efficacy, and to minimize the occurrence of side effects.
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Paragraph 0136; 0137
(2020/02/18)
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- Anti-tumor compound as well as preparation method and application thereof
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The invention belongs to the technical field of medicines and in particular relates to an anti-tumor compound as well as a preparation method and application thereof. The anti-tumor compound providedby the invention has a molecular structure shown as a fo
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Paragraph 0062; 0063; 0064; 0065
(2019/01/21)
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- Thiosemicarbazone Dynamic Combinatorial Chemistry: Equilibrator-Induced Dynamic State, Formation of Complex Libraries, and a Supramolecular On/Off Switch
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Dynamic combinatorial libraries that equilibrate under thermodynamic control and can be trapped kinetically when desired are key to creating complex systems that can mimic dynamic biological systems, such as the biochemical system of life. A much-sought-after feature is the ability to turn off the dynamic exchange of the system, in order to investigate a transient state away from thermodynamic equilibrium, and then turn on the dynamic exchange again. We describe here the first use of thiosemicarbazone exchange to form dynamic combinatorial libraries. The libraries were found to require a nucleophilic catalyst, or equilibrator, in order to reach thermodynamic equilibrium. This equilibrator approach adds a supramolecular level of control over the dynamic system and allows the dynamic exchange to be turned off by addition of 18-crown-6, which binds the equilibrator in a nonnucleophilic complex. The dynamic exchange can be restarted by addition of potassium ions that competitively bind 18-crown-6, thus liberating the equilibrator. The highly complex thiosemicarbazone-based macrocyclic libraries contain both [2]catenanes and sequence isomers, which can be distinguished by HPLC-MS/MS.
- Larsen, Dennis,Jeppesen, Anne,Kleinlein, Claudia,Pittelkow, Michael
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p. 8580 - 8589
(2017/08/23)
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- Synthesis of salicylaldehydes from phenols via copper-mediated duff reaction
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A copper-mediated Duff reaction for ortho-selective formylation of phenols has been developed. In the presence of copper species, significant improvements of yield and ortho-selectivity of the Duff formylation were achieved, which provides an easy access to salicylaldehydes from phenols.
- Fu, Xue-Wen,Pu, Wen-Chen,Zhang, Guo-Lin,Wang, Chun
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p. 8147 - 8158
(2015/02/19)
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- 1-PHENYL-2-PYRIDINYL ALKYL ALCOHOL DERIVATIVES AS PHOSPHODIESTERASE INHIBITORS
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Compounds of formula (I) described herein are inhibitors of the phosphodiesterase 4 (PDE4) enzyme and are useful for the prevention and/or treatment of an allergic disease state or a disease of the respiratory tract characterized by airway obstruction.
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Paragraph 0632; 0633
(2014/06/23)
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- POLYMERIZABLE CHIRAL COMPOUND, POLYMERIZABLE LIQUID CRYSTAL COMPOUND, LIQUID CRYSTAL POLYMER AND OPTICALLY ANISOTROPIC BODY
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The present invention is to provide a novel polymerizable chiral compound (chiral agent) having high left-handed helical twisting power, a polymerizable liquid crystal composition comprising the polymerizable chiral compound and a polymerizable liquid crystal compound, a liquid crystal polymer, and an optically anisotropic body. The object was achieved by a left-handed-helix-inducing polymerizable chiral compound represented by the following formula (I), a polymerizable liquid crystal composition comprising the polymerizable chiral compound and a polymerizable liquid crystal compound, a liquid crystal polymer and an optically anisotropic body: wherein X represents the following formula (X-i) or (X-ii) wherein * represents a bond: wherein Y1 to Y6 are each one selected from the group consisting of —O—, —S—, —O—C(═O)—, —C(═O)—O— and so on; Yx is one selected from the group consisting of —C(═O)—, —O—C(═O)—, —CH═CH—C(═O)—, —CH2— and so on; Yz is one selected from the group consisting of —C(═O)—, —C(═O)—O—, —C(═O)—CH═CH— and so on; G1 and G2 are each a divalent aliphatic group which has 1 to 20 carbon atoms and which may have a substituent; Z1 and Z2 are each an alkenyl group which has 2 to 10 carbon atoms and which may be substituted by a halogen atom; Q1 to Q4 are each a hydrogen atom or an alkyl group which has 1 to 6 carbon atoms and which may have a substituent; A1 to A6 are each a divalent organic group having 1 to 30 carbon atoms; and a and b are each 0 or 1.
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Paragraph 0258
(2013/03/26)
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- Studies on benzofuran-7-carboxamides as poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors
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Benzofuran-7-carboxamide was identified as a novel scaffold of poly(ADP-ribose) polymerase-1 (PARP-1) inhibitor. A series of compounds with various 2-substituents including (tertiary amino)methyl moieties substituted with aryl ring and aryl groups containing tertiary amines, were synthesized and biologically evaluated to elucidate the structure-activity relationships and optimize the potency. 2-[4-(Pyrrolidin-1-ylmethyl)phenyl]-benzofuran-7- carboxamide (42) was the most potent as an IC50 value of 40 nM among those.
- Lee, Sunkyung,Yi, Kyu Yang,Lee, Byung Ho,Oh, Kwang Seok
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scheme or table
p. 1147 - 1153
(2012/07/14)
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- POLYMERIZABLE CHIRAL COMPOUND, POLYMERIZABLE LIQUID CRYSTALLINE COMPOSITION, LIQUID CRYSTALLINE POLYMER, AND OPTICAL ISOMER
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The present inventions to provide a novel polymerizable chiral compound (chiral agent) having high helical twisting power, a polymerizable liquid crystal composition comprising the polymerizable chiral compound and a polymerizable liquid crystal compound,
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Page/Page column 22
(2011/06/26)
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- NOVEL COMPOUNDS
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The present invention discloses novel compounds inhibiting LRRK2 kinase activity, the preparation processes thereof, the compositions containing them, as well as the use in treating diseases characterized by LRRK2 kinase activity, particularly Parkinson's disease and Alzheimer's disease.
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Page/Page column 79
(2011/04/25)
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- POLYMERIZABLE LIQUID CRYSTAL COMPOUND, POLYMERIZABLE LIQUID CRYSTAL COMPOSITION, LIQUID CRYSTALLINE POLYMER, AND OPTICALLY ANISOTROPIC MATERIAL
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A polymerizable liquid crystal compound shown by the following formula (I), a polymerizable liquid crystal composition that includes the polymerizable liquid crystal compound and a chiral compound polymerizable with the polymerizable liquid crystal compou
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Page/Page column 29
(2010/01/29)
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- SUBSTITUTED-QUINOXALINE-TYPE-PIPERIDINE COMPOUNDS AND THE USES THEREOF
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The invention relates to Substituted-Quinoxaline-Type Piperidine Compounds, compositions comprising an effective amount of a Substituted-Quinoxaline-Type Piperidine Compound and methods to treat or prevent a condition, such as pain, comprising administeri
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Page/Page column 232
(2009/04/25)
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- A one-pot synthesis of unsymmetrical bis-styrylbenzenes
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An efficient and widely applicable one-pot synthesis of unsymmetrical (E,E)-bis-styrylbenzenes using successive Heck and Horner-Wadsworth-Emmons reactions is described.
- Flaherty, Daniel P.,Dong, Yuxiang,Vennerstrom, Jonathan L.
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supporting information; experimental part
p. 6228 - 6230
(2010/01/18)
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- Synthetic strategies to derivatizable triphenylamines displaying high two-photon absorption
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(Chemical Equation Presented) A versatile synthetic strategy to access a set of highly fluorescent π-conjugated triphenylamines bearing a functional linker at various positions on one phenyl ring is described. These compounds were designed for large two-photon absorption (2PA) and in particular for labeling of biomolecules. The monoderivatized trisformylated or trisiodinated intermediates described herein allow introduction of a large variety of electron-withdrawing groups required for large 2PA as well as a panel of chemical functions suitable for coupling to biomolecules. The monoderivatized three-branched compounds and in particular the benzothiazole (TP-3Bz) series show remarkable linear (high extinction coefficients and high quantum yield) and nonlinear (high 2-photon cross sections) optical properties. Interestingly the presence of functional side chains does not disturb the two-photon absorption. Finally, monoderivatized two-branched derivatives also appear to be valuable candidates. Altogether the good optical properties of the new derivatizable π-conjugated TPA combined with their small size and their compatibility with bioconjugation protocols suggest that they represent a new chemical class of labels potentially applicable for the tracking of biomolecules using two-photon scanning microscopy.
- Lartia, Remy,Allain, Clemence,Bordeau, Guillaume,Schmidt, Falk,Fiorini-Debuisschert, Celine,Charra, Fabrice,Teulade-Fichou, Marie-Paule
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p. 1732 - 1744
(2008/09/18)
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- Derivatives of 1,4-bis(3-hydroxycarbonyl-4-hydroxyl)styrylbenzene as PTP1B inhibitors with hypoglycemic activity
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Disalicylic acid derivatives with stilbene and bis-styrylbenzene skeleton were synthesized as PTP1B inhibitors. The most potent in this series exhibited a submicromolar IC50 value. One of the compounds 7b was tested in an animal model for its efficacy as an anti-diabetic or an anti-obesity agent. In feeding compound 7b to diet-induced obese mice, no significant differences in weight gain and food consumption were observed between the drug-treated and the obese control mice. However, 7b significantly lowered the fasting glucose level and improved the glucose tolerance in the obesity-induced diabetic mice.
- Shrestha, Suja,Bhattarai, Bharat Raj,Kafle, Bhooshan,Lee, Keun-Hyeung,Cho, Hyeongjin
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p. 8643 - 8652
(2008/12/23)
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- 4-Phenyl-5-Oxo-1,4,5,6,7,8,- Hexahydroquinoline Derivatives as Medicaments for the Treatment of Infertility
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The invention relates to a 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivative according to Formula (I), wherein the substituents are defined as in the description, or a pharmaceutically salt thereof. The compounds of this invention are potent FSH receptor activators and may be used for treating fertility disorders in e.g. controlled ovarian hyperstimulation and IVF procedures.
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Page/Page column 27
(2009/01/20)
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- An efficient preparation and some reactions of 2-dimethylaminomethylene-1, 3-bis(dimethylimonio)propane diperchlorate
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An alternative preparation of 2-dimethylaminomethylene-1,3- bis(dimethylimonio)propane diperchlorate from malonic acid is described along with its application to the synthesis of 2,4,6-trisubstituted phenols and 2-(N-(2,2-diformylethenyl)amino)pyridine.
- Jameleddine, Khiari,Adnen, Hadj Ayed Med,Béchir, Ben Hassine
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p. 2973 - 2975
(2007/10/03)
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- COMPOUNDS AND METHODS FOR TREATING DYSLIPIDEMIA
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Compounds of Formula (I): wherein n, m, p, q, Y, R1 R2, R3a, R3b, R4, R5, and R6 are as defined herein and their pharmaceutical compositions and methods of use are disclosed.
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Page/Page column 213-214
(2010/02/15)
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- 4-PHENYL-5-OXO-l,4,5,6,7,8-HEXAHYDROQUINOLINE DERIVATIVES AS MEDICAMENTS FOR THE TREATMENT OF INFERTILITY
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The invention relates to a 4-phenyl-5-oxo-l,4,5,6,7,8-hexahydroquinoline derivative according to Formula (I), wherein the substituents are defined as in the description, or a pharmaceutically salt thereof. The compounds of this invention are potent FSH receptor activators and may be used for treating fertility disorders in e.g. controlled ovarian hyperstimulation and IVF procedures.
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Page/Page column 45-46
(2008/06/13)
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- Demonstrating the Synergy of Synthetic, Mechanistic, and Computational Studies in A Regioselective Aniline Synthesis
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Tri- and tetrasubstituted anilines are formed in good to excellent yields by the addition of ketones to vinamidinium salts (up to 98%). The reaction proceeds via the formation of dienone intermediates, which react to form an enamine with the liberated amine. In the case of a nitro, or dimethylaminomethylene substituent, the enamines undergo a facile electrocyclic ring closure to form a cyclohexadiene, which goes on to form anilines with a high degree of selectivity (up to 50:1) with a minor competing pathway proceeding via the enol providing phenols. Competition experiments using isotopic substitution reveal that the rate determining step en route to dienone is enol/enolate addition to the vinamidinium salt, which is characterized by an inverse secondary isotope effect (kH/D 0.7-0.9). Computational studies have been used to provide a framework for understanding the reaction pathway. The original proposal for a [1,5]-H shift was ruled out on the basis of the calculations, which did not locate a thermally accessible transition state. The minimum energy conformation of the enamine is such that a facile electrocyclic ring closure is ensured, which is corroborated by the experimental studies. A framework for understanding the reaction pathway is presented.
- Davies, Ian W.,Marcoux, Jean-Francois,Kuethe, Jeffery T.,Lankshear, Michael D.,Taylor, Jeremy D. O.,Tsou, Nancy,Dormer, Peter G.,Hughes, David L.,Houk,Guner, Vildan
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p. 1298 - 1308
(2007/10/03)
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- An efficient synthesis of 2-(3-(4-amidinophenylcarbamoyl)naphthalen-2-yl)-5-((2,2-methylpro pyl)carbamoyl)benzoic acid: A factor VIIa inhibitor discovered by the Ono Pharmaceutical Company
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A small molecule factor VIIa inhibitor has recently been reported by the Ono Pharmaceutical Company. Herein, we outline an efficient and convergent, synthetic route that relies upon a palladium-catalyzed Stille coupling reaction as a key step for the synt
- Kohrt,Filipski,Rapundalo,Cody,Edmunds
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p. 6041 - 6044
(2007/10/03)
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- Synthesis of fluorovinylsalicylic acids and their derivatives
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Palladium-catalyzed cross-coupling of iodosalicylic acid derivatives with polyfluorovinyl zinc reagents provided the corresponding fluorovinyl-substituted salicylates.Methyl-5-(β,β)-difluorovinyl methyl salicylate was prepared by a Wittig reaction of the 5-formyl compound with the strongly nucleophilic ylide, .In one sequence, a fluorine-free benzofuran was obtained, instead of a difluorovinylsalicylate. - Keywords: Fluorovinylsalicylic acids; Wittig reaction; Benzofuran
- Filler, Robert,Lin, Shan,Zhang, Zhaoxu
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