- Spontaneous reaction of malonyl peroxides with methanol
-
The spontaneous reaction of disubstituted malonyl peroxides (MPOs) with methanol affording monopermalonic acid monomethyl esters is fast (minutes) for lower homologues but is sharply decelerated (days) for the higher ones. Spirocyclopropyl-MPO is an excep
- Lapitskaya, Margarita A.,Vil, Vera A.,Vasil'eva, Ludmila L.,Daeva, Elena D.,Terent'ev, Alexander O.,Pivnitsky, Kasimir K.
-
-
Read Online
- Practical synthesis of a heterocyclic immunosuppressive vitamin D analogue
-
1α,25-Dlhydroxyvitamin D3 (calcitrioi) 1 and synthetic analogues thereof are highly potent compounds with a wide range of pharmacological activity making them of great interest for the pharmaceutical industry. Herein we report an improved synthesis of the calcitriol analogue 2, which features a novel oxazole-containing side chain. The crucial part of the synthesis was the development of a practical route to the β-keto phosphonate 28, allowing an easy introduction of the unnatural side chain by a Wittig Horner reaction.
- Westermann, Juergen,Schneider, Matthias,Platzek, Johannes,Petrov, Orlin
-
-
Read Online
- Alcoholysis of malonyl peroxides to give peracids
-
Potassium acetate catalyzed alcoholysis of spirocycloalkyl malonyl peroxides affords 1-alkoxycarbonylcycloalkane-1-percarboxylic acids which are suitable for epoxidation of olefins.
- Lapitskaya, Margarita A.,Vil', Vera A.,Daeva, Elena D.,Terent'Ev, Alexander O.,Pivnitsky, Kasimir K.
-
-
Read Online
- Synthesis and anti-tumor activity of [1,4] dioxino [2,3-f] quinazoline derivatives as dual inhibitors of c-Met and VEGFR-2
-
Both c-Met and VEGFR-2 were important targets for cancer therapies. In order to develop reversible and non-covalent c-Met and VEGFR-2 dual inhibitors, a series of [1,4]dioxino[2,3-f]quinazoline derivatives were designed and synthesized. The enzyme assay demonstrated that most target compounds had inhibition potency on both c-Met and VEGFR-2 with IC50 values in nanomolar range especially compounds 7m and 7k. Based on further cell proliferation assay in vitro, compound 7k showed significantly anti-tumor activity in vivo on a hepatocellular carcinoma (MHCC97H cells) xenograft mouse model. We docked the compound 7m with c-Met and VEGFR-2 kinases, and interpreted the SAR of these analogues. All results indicated that the target compounds were dual inhibitors of c-Met and VEGFR-2 kinases that held promising potential in cancer therapy.
- Wei, Dengshuai,Fan, Haoru,Zheng, Kun,Qin, Xuemei,Yang, Leifu,Yang, Yajuan,Duan, Ye,Zhang, Qiang,Zeng, Chengchu,Hu, Liming
-
-
- PYRIDO-AZAHETERECYDIC COMPOUND AND PREPARATION METHOD AND USE THEREOF
-
The present invention discloses a pyrido-azacyclic compound represented by formula I, an isomer thereof, a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof, a preparation process thereof and a composition comprising the compound, and a use thereof as a multi-target protein kinase inhibitor in the preparation of a medicament for the treatment of diseases that are associated with protein kinase, especially c-Met, such as cancer and the like. The compound represented by formula I has potent inhibitory activity on tumor cells with overexpression of c-Met kinase, can effectively target c-Met-mediated signaling pathway, and can be used in the treatment of diseases such as cancer and the like that is caused by the overexpression of c-Met kinase.
- -
-
Paragraph 0066
(2018/09/21)
-
- A tyrosine kinase inhibitor and wherein the intermediate preparation method
-
The invention relates to a preparation method for a tyrosine kinase inhibitor and a midbody thereof. According to the method, a compound 1,1-cyclopropane dicarboxylic acid diester is taken as a raw material, and 1-((4-((6,7-dimethoxy quinoline-4-yl) oxy)
- -
-
Paragraph 0069; 0070; 0071
(2016/10/10)
-
- AROMATIC HETEROCYCLIC COMPOUND
-
The compound represented by the general formula: wherein ring A is benzene which may be substituted and the like; ring B is benzene which may be substituted and the like; X is a single bond and the like; Y is alkyl which may be substituted and the like; Z is CR1 or nitrogen atom; R1 is hydrogen and the like; R2 is alkyl which may be substituted and the like or a pharmaceutically acceptable salt thereof is useful as a prevention/treatment agent of obesity, diabetes, and the like.
- -
-
Paragraph 1283; 1284
(2015/05/05)
-
- NON-SYSTEMIC TGR5 AGONISTS
-
Compounds of structure (I), or a stereoisomer, tautomer, pharmaceutically acceptable salt or prodrug thereof, wherein R1, R2, R3, R4, R8, R9, R10, R11, R12, A1, A2, X, Y and Z are as defined herein. Uses of such compounds as TGR5 antagonists and for treatment of various indications, including Type II diabetes meletus are also provided.
- -
-
Page/Page column 229
(2013/07/05)
-
- OXAZOLO [5, 4 -B] PYRIDIN- 5 -YL COMPOUNDS AND THEIR USE FOR THE TREATMENT OF CANCER
-
The present invention provides oxazolo[5,4-b]pyridin-5-yl compounds useful in the treatment of cancer.
- -
-
Page/Page column 20-21
(2012/06/16)
-
- Multicomponent synthesis of pyrroles from cyclopropanes: A one-pot palladium(0)-catalyzed dehydrocarbonylation/dehydration
-
Ring the changes: The cycloaddition of nitrones with 1-carboallyloxy-1- carbomethoxycyclopropanes yields tetrahydro-1,2-oxazines, which in turn undergo a Tsuji dehydrocarbonylation to give dihydro-1,2-oxazines (see scheme; dba=dibenzylideneacetone). Addition of base to this reaction mixture results in clean conversion to pyrroles. The result is a flexible three-component strategy for the synthesis of tetrasubstituted pyrroles. Copyright
- Humenny, William J.,Kyriacou, Polydoros,Sapeta, Katarina,Karadeolian, Avedis,Kerr, Michael A.
-
supporting information
p. 11088 - 11091
(2013/01/15)
-
- Nucleophilic ring opening of cyclopropane hemimalonates using internal Bronsted acid activation
-
The reaction of cyclopropanes, geminally disubstituted with one carboalkoxy and one carbohydroxy group, undergoes ring-opening reactions with indole nucleophiles under catalyst-free, hyperbaric (13 kbar) conditions. An internal hydrogen bond is postulated
- Emmett, Michael R.,Kerr, Michael A.
-
supporting information; experimental part
p. 4180 - 4183
(2011/10/02)
-
- NOVEL PIPERAZINE DERIVATIVES AS INHIBITORS OF STEAROYL-CoA DESATURASE
-
The present invention relates to piperidine derivatives that act as inhibitors of stearoyl-CoA desaturase. The invention also relates to methods of preparing the compounds, compositions containing the compounds, and to methods of treatment using the compounds.
- -
-
Page/Page column 55
(2009/10/01)
-
- NOVEL PIPERAZINE DERIVATIVES AS INHIBITORS OF STEAROYL-CoA DESATURASE
-
The present invention relates to piperazine derivatives that act as inhibitors of stearoyl-CoA desaturase. The invention also relates to methods of preparing the compounds, compositions containing the compounds, and to methods of treatment using the compounds.
- -
-
Page/Page column 33
(2009/10/01)
-
- Asymmetric approach to the pentacyclic skeleton of Aspidosperma alkaloids via enantioselective intramolecular 1,3-dipolar cycloaddition of carbonyl ylides catalyzed by chiral dirhodium(II) carboxylates
-
This Letter describes asymmetric tandem carbonyl ylide formation-intramolecular 1,3-dipolar cycloaddition reaction of diazo imides containing a tethered indole catalyzed by chiral dirhodium(II) carboxylates as an approach to the pentacyclic skeleton of Aspidosperma alkaloids. The cycloaddition of carbonyl ylides derived from indolyl-substituted 2-diazo-5-imido-3-ketoesters under the influence of dirhodium(II) tetrakis[N-tetrachlorophthaloyl-(S)-tert-leucinate], Rh2(S-TCPTTL)4, provides cycloadducts in moderate yields and enantioselectivities of up to 66% ee as well as with perfect endo diastereoselectivity. This is the first example of asymmetric induction in an intramolecular cycloaddition of a carbonyl ylide across an indolyl π-bond.
- Nambu, Hisanori,Hikime, Mayuka,Krishnamurthi, Janagiraman,Kamiya, Megumi,Shimada, Naoyuki,Hashimoto, Shunichi
-
supporting information; experimental part
p. 3675 - 3678
(2009/10/04)
-
- Preparation and affinity profile of novel nicotinic ligands
-
Novel nicotinic ligands, characterized by the presence of an amino substituted cyclopropane ring connected to a pyridine nucleus, are described. Pharmacological investigation revealed that these compounds exhibit highest affinity for the rat α4β2 subtype of the nicotinic receptor with no affinity for the muscarinic receptor. No appreciable affinity for the muscular or for the ganglionic nicotinic receptor was observed at concentrations up to 10 μM. The increase in cortical ACh release as well as a positive effect on memory in a social recognition test in rat are exemplified.
- Charton, Yves,Guillonneau, Claude,Lockhart, Brian,Lestage, Pierre,Goldstein, Solo
-
p. 2188 - 2193
(2008/12/22)
-
- SPIRO SUBSTITUTED COMPOUNDS AS ANGIOGENESIS INHIBITORS
-
The present invention relates to spiro (tetracarbon) substituted compound of Formula I, processes for their preparation, pharmaceutical compositions containing them as active ingredient, methods for the treatment of disease states associated with angiogenesis, such as cancers associated with protein tyrosine kinases, to their use as medicaments for use in the production of inhibition of tyrosine kinases reducing effects in warm-blooded animals such as humans
- -
-
Page/Page column 20
(2008/12/07)
-
- Spiro Substituted Compounds As Angiogenesis Inhibitors
-
The present invention relates to spiro (tetracarbon) substituted compound of Formula I, processes for their preparation, pharmaceutical compositions containing them as active ingredient, methods for the treatment of disease states associated with angiogenesis, such as cancers associated with protein tyrosine kinases, to their use as medicaments for use in the production of inhibition of tyrosine kinases reducing effects in warm-blooded animals such as humans.
- -
-
Page/Page column 17-18
(2008/12/07)
-
- DIAMINE DERIVATIVES
-
A compound represented by formula (1):Q1-Q2-To-N(R1) -Q3-N(R2)-T1-Q4 [wherein R1 and R2 are hydrogen atoms or the like; Q1 is a saturated or unsaturated, 5- or 6- membered cyclic hydrocarbon group which may be substituted, or the like; Q2 is a single bond or the like; Q3 represents the following group: (wherein Q5 is an alkylene group having 1 to 8 carbon atoms, or the like); and T0 and T1 are carbonyl groups or the like], a salt thereof, a solvate thereof, or an N-oxide thereof. The compound is useful as an agent for preventing and/or treating cerebral infarction, cerebral embolism, myocardial infarction, angina pectoris, pulmonary infarction, pulmonary embolism, Buerger's disease, deep venous thrombosis, disseminated intravascular coagulation syndrome, thrombus formation after artificial valve or joint replacement, thrombus formation and reocclusion after angioplasty, systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), thrombus formation during extracorporeal circulation, or blood clotting upon blood drawing.
- -
-
Page/Page column 148
(2008/06/13)
-
- Diamine derivatives
-
A compound represented by the general formula (1): Q1-Q2-T0-N(R1)-Q3-N(R2)-T1-Q4??(1) wherein R1 and R2 are hydrogen atoms or the like; Q1 is a saturated or unsaturated, 5- or 6-membered cyclic hydrocarbon group which may be substituted, or the like; Q2 is a single bond or the like; Q3 is a group in which Q5 is an alkylene group having 1 to 8 carbon atoms, or the like; and T0 and T1 are carbonyl groups or the like; a salt thereof, a solvate thereof, or an N-oxide thereof. The compound is useful as an agent for preventing and/or treating cerebral infarction, cerebral embolism, myocardial infarction, angina pectoris, pulmonary infarction, pulmonary embolism, Buerger's disease, deep venous thrombosis, disseminated intravascular coagulation syndrome, thrombus formation after valve or joint replacement, thrombus formation and reocclusion after angioplasty, systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), thrombus formation during extracorporeal circulation, or blood clotting upon blood drawing.
- -
-
-
- DIAMINE DERIVATIVES
-
A compound represented by the general formula (1):Q1-Q2-T0-N(R1)-Q3-N(R2)-T1-Q4 wherein R1 and R2 are hydrogen atoms or the like; Q1 is a saturated or unsaturated, 5- or 6- membered cyclic hydrocarbon group which may be substituted, or the like; Q2 is a single bond or the like; Q3 is a group in which Q5 is an alkylene group having 1 to 8 carbon atoms, or the like; and T0 and T1 are carbonyl groups or the like; a salt thereof, a solvate thereof, or an N-oxide thereof. The compound is useful as an agent for preventing and/or treating cerebral infarction, cerebral embolism, myocardial infarction, angina pectoris, pulmonary infarction, pulmonary embolism, Buerger's disease, deep venous thrombosis, disseminated intravascular coagulation syndrome, thrombus formation after valve or joint replacement, thrombus formation and reocclusion after angioplasty, systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), thrombus formation during extracorporeal circulation, or blood clotting upon blood drawing.
- -
-
-
