- PYRIDOPYRIMIDINE COMPOUNDS ACTING AS MTORC 1/2 DOUBLE-KINASE INHIBITORS
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Disclosed are a series of pyridopyrimidine compounds and a use of same in the preparation of drugs associated with mTORC 1/2 dual complex inhibitors, and specifically disclosed is a use of the compounds as shown in formula (IV), tautomers thereof or pharmaceutically acceptable salts thereof in the preparation of drugs associated with mTORC 1/2 dual complex inhibitors.
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Paragraph 0256-0258
(2020/11/30)
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- Volution lactone compound and synthesis method and application thereof
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The invention discloses a volution lactone compound. The chemical structural formula of the volution lactone compound is shown in the specification. A preparing method of the volution lactone compound includes the steps that (1) cyclopentanone serves as a raw material and is subjected to a cyanohydrintion reaction, then cyano groups are hydrolyzed and esterified, and hydroxyl-cyclopentanecarboxylic acid ethyl ester is obtained; (2) a sulfonation reaction is carried out; (3) a butt joint ring formation reaction is carried out; (4) an alkylation reaction is carried out, wherein the cyclizing product obtained in the step (3), a reaction solvent and a catalyst are mixed, 3-bromopropylene is added into the mixed liquid, the solvent is removed in a pressure-reduction mode after reacting, water and benzene are added, extracting and layering are carried out, an organic phase substance is obtained, solvent pressure-reduction removing and filtering are carried out, and the final product volution lactone compound is obtained. The volution lactone compound has the advantage that a pesticide good in pest killing effect, long in lasing period and low in toxicity is obtained.
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Paragraph 0048-0049
(2017/05/12)
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- HIV PROTEASE INHIBITORS
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The present invention is directed to 2,6-morpholine derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein Z1, Z2, V1, V2, V3, R6, R6A, and X are defined herein. The invention also relates to methods of using the 2,6-morpholine derivatives of the invention for the inhibition of HV protease, the inhibition of HV replication, the prophylaxis of infection by HIV, the treatment of infection by HIV, and the prophylaxis, treatment, and delay in the onset or progression of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.
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Paragraph 0564; 0565
(2017/08/26)
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- Anesthetic compounds and related methods of use
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Provided herein are compounds according to formula (I): Provided herein is also a pharmaceutical composition comprising a compound according to formula (I) and a pharmaceutically acceptable carrier, and a method for providing anesthesia in a subject by administering such a pharmaceutical composition.
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Page/Page column 64
(2015/11/09)
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- Synthesis, spectral, and structural characteristics of cyanohydrines derived from aliphatic cyclic ketones1
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A series of cyanohydrines derived from cyclic aliphatic ketones was synthesized by acid-catalyzed nucleophilic addition reaction under the action of potassium cyanide. The products were characterized by means of multi-nuclear NMR spectroscopy (1H, 13C, 14N, 15N), mass spectrometry, elemental analysis, UV-Vis spectroscopy, refraction index measurements as well as vibrational spectroscopy. The structure of the cyanohydrine of cyclohexanone was elucidated by means of single crystal X-ray diffraction.
- Hosten,Betz
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p. 2222 - 2227
(2015/02/02)
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- Novel 4H-1,2,4-triazol-3-yl cycloalkanols as potent antitubercular agents
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Enzymes of shikimate pathway, dehydroquinase and shikimate kinase represent comparatively newer targets for antitubercular research. Molecular hybridization approach was implemented by integrating the essential features of inhibitors acting on these enzymes of shikimate pathway. Considering the flexibility of alicyclic ring of reported dehydroquinase (DHQ) inhibitors and triazole ring, key feature of the virtual hits of Mtb shikimate kinase, a series of structurally novel, substituted 4H-1,2,4-triazol-3-yl cycloalkanols were designed as antimycobacterial agents. Docking studies of the molecules was carried out on the enzyme DHQ. All the synthesized compounds exhibited promising activity (MIC 0.59-15.5 μg/ml) against H37Rv strains of Mycobacterium tuberculosis using resazurin microtiter assay. Five of the evaluated compounds exhibit MIC 50 values indicate compounds are non-toxic, with selectivity indices >28. These compounds could serve as leads for further optimization to obtain novel antimycobacterial agents.
- Desai, Nutan H. Palsule,Bairwa, Ranjeet,Kakwani, Manoj,Tawari, Nilesh,Ray,Rajan,Degani, Mariam
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p. 401 - 408
(2013/03/13)
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- ANESTHETIC COMPOUNDS AND RELATED METHODS OF USE
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Provided herein are compounds according to formula (I): Provided herein is also a pharmaceutical composition comprising a compound according to formula (I) and a pharmaceutically acceptable carrier, and a method for providing anesthesia in a subject by administering such a pharmaceutical composition.
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Paragraph 00199
(2013/07/25)
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- Asymmetric synthesis of both the enantiomers of antidepressant venlafaxine and its analogues
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Chemoenzymatic asymmetric synthesis of antidepressant agent venlafaxine and its analogue have been reported in this communication. The main highlight of the reported synthesis is the stereoselective synthesis of cyanohydrins by (S)-hydroxynitrile lyase (Hevea brasiliensis) followed by lipase catalyzed kinetic resolution.
- Bhuniya, Rajib,Nanda, Samik
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scheme or table
p. 1990 - 1992
(2012/05/05)
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- BENZAMIDE DERIVATIVES AS P2X7 RECEPTOR ANTAGONISTS
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The invention relates to benzamide derivatives of formula (I),wherein R1, R2, R3, R4, R5, R6, n and Y are as defined in the description, their preparation and their use as pharmaceutically active compounds.
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Page/Page column 77
(2012/09/11)
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- Bradykinin B1 receptor antagonists: An α-hydroxy amide with an improved metabolism profile
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A series of carbo- and heterocyclic α-hydroxy amide-derived bradykinin B1 antagonists was prepared and evaluated. A 4,4-difluorocyclohexyl α-hydroxy amide was incorporated along with a 2-methyl tetrazole in lieu of an oxadiazole to afford a suitable compound with good pharmacokinetic properties, CNS penetration, and clearance by multiple metabolic pathways.
- Kuduk, Scott D.,Chang, Ronald K.,DiPardo, Robert M.,Di Marco, Christina N.,Murphy, Kathy L.,Ransom, Richard W.,Reiss, Duane R.,Tang, Cuyue,Prueksaritanont, Thomayant,Pettibone, Douglas J.,Bock, Mark G.
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scheme or table
p. 5107 - 5110
(2009/05/26)
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- Reactivity of the 4-amino-5H-1,2-oxathiole-2,2-dioxide heterocyclic system: A combined experimental and theoretical study
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The reactivity of the 4-amino-5H-1,2-oxathiole-2,2-dioxide (or β-amino-γ-sultone) heterocyclic system has scarcely been studied. Here we describe the reactivity of this system towards electrophiles and amines on readily available model substrates differently substituted at the C-5 position. A variety of C-electrophiles, carbonyl electrophiles (such as acyl chlorides, isocyanates, or aldehydes) and halogen or nitrogen electrophiles have been explored. Both the C-3 and 4-amino positions of the β-amino-γ- sultone system are able to undergo electrophilic reactions, and the reaction products depend on the electrophile used and on the reaction conditions. On the other hand, nucleophilic attack of amines occurs at the C-4 position of the β-amino-γ-sultone system only in spiranic substrates bearing alicyclic substituents at the C-5 position. A comparative computational study between spiranic and non-spiranic substrates suggests that conformational changes, undergone on intermediate compounds, account for the observed reactivity differences. Moreover, these conformational changes seem to bring about an increase of electron density on the N-4 and C-3 atoms of the enaminic system, and a possible enhancement in the reactivity of spiranic substrates towards electrophiles in the presence of amines. Experimental data consistent with this predicted enhanced reactivity is also presented.
- De Castro, Sonia,Teresa Peromingo,Lozano, Angel E.,Camarasa, Maria-Jose,Velazquez, Sonsoles
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supporting information; experimental part
p. 9620 - 9632
(2009/10/01)
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- Oxazolones as potent inhibitors of 11β-hydroxysteroid dehydrogenase type 1
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2,5,5-Trisubstituted oxazolones were identified as potent inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). The synthesis, structure-activity relationship and metabolic stability of these compounds are presented.
- Sutin, Lori,Andersson, Soeren,Bergquist, Lars,Castro, Victor M.,Danielsson, Eva,James, Stephen,Henriksson, Martin,Johansson, Lars,Kaiser, Christina,Flyren, Katarina,Williams, Meredith
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p. 4837 - 4840
(2008/02/11)
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- l-HYDROXYCYCLOALKANECARBOXAMIDE DERIVATIVES AS BRADYKININ ANTAGONISTS
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α-Hydroxycycloalkanecarboxamide derivatives of formula (I) or a pharmaceutically acceptable salt thereof, wherein formula (a) is a single or double bond; Rl, R2 and R3 are each independently selected from H, halogen and OH; or Rl and R2 attached to the same carbon atom together represent oxo; R4 is H or methyl; R5 is Cl or F; R6 is selected from -CO2-C1-4alkyl, -O-C1-4alkyl, -O- C1-4haloalkyl, 2-methyltetrazol-5-yl, 5-methyl l,2,4-oxadiazol-3-yl, 3-methyl-1,2,4-oxadiazol-5-yl, 5-halomethyl-l,2,4-oxadiazol-3-yl, 3-halomethyl- l,2,4-oxadiazol-5-yl, tetrazol-5-yl, 5-halomethyl-l,2,3-triazolyl, and 5-methyl-l ,2,3-triazolyl; R7 and R8 are each independently Cl or F; and n is 0 or 1, are bradykinin B1 antagonists or inverse agonists useful in the treatment or prevention of symptoms such as pain and inflammation associated with the bradykinin B1 pathway.
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Page/Page column 23-25
(2008/06/13)
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- Spirodiclofen and spiromesifen - Novel acaricidal and insecticidal tetronic acid derivatives with a new mode of action
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The broad spectrum acaricides spirodiclofen (BAJ2740, trade name: Envidor) and spiromesifen (BSN2060, trade name: Oberon) with an additional excellent activity against whiteflies, both belong to the new chemical class of tetronic acid derivatives discovered at Bayer CropScience during the 1990s. The discovery process starting from herbicidal PPO (protoporphyrinogen oxidase) chemistry, the synthetic routes leading to the products, and some insight into process development of central intermediates is given. Spirodiclofen and spiromesifen have a new mode of action (interference with lipid biosynthesis), show no cross-resistance to any resistant mite or whitefly field population and are therefore valuable tools for resistance management.
- Bretschneider, Thomas,Benet-Buchholz, Jordi,Fischer, Reiner,Nauen, Ralf
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p. 697 - 701
(2007/10/03)
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- Studies on phosphoroheterocycle chemistry III: An unusual way to 1,3,2-thiazaphospholidine-4-thione 2-sulfide derivatives
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An unusual but efficient method for the synthesis of phosphoroheterocycles, 1,3,2-thiazaphospholidine-4-thione 2-sulfide derivatives, by the reaction of Lawesson's reagent with a variety of α-hydroxy nitriles has been developed. The possible mechanism of the reaction is proposed to involve thiation of hydroxy group in a first step, sequential addition of P-SH to the nitrile and rearrangement resulting in the title phosphoroheterocycles. The preliminary bioassays show that these heterocyclic compounds have herbicidal properties.
- Deng, ShengLou,Chen, RuYu
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p. 2527 - 2531
(2007/10/03)
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- Addition of diphenylphosphine to Michael-type olefins: the preparation of phosphine-nitrile and phosphine-ester ligands
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The reactions of five Michael-type olefins with diphenylphosphine have been carried out. 1-Cyanocyclopentene, 1-cyanocyclohexene, and 4-t-butyl-1-cyanocyclohexene all provide the corresponding 2-diphenylphosphino-1-cyanocycloalkanes, and both methyl acrylate and ethyl methacrylate yield to corresponding 2-diphenylphosphinopropionates.For the products from 1-cyanocyclopentene and 1-cyanocyclohexene, 13C and 31P NMR data are consistent with the formation of both trans (Ph2P equatorial and CN axial) and cis (both Ph2P and CN equatorial) isomers.The morpholine amide of 3-diphenylphosphinopropionic acid has been obtained by treatment of methyl-3-diphenylphosphinopropionate with the dimethylaluminum adduct of morpholine.This phosphine, Ph2Pmorph, has been isolated as its palladium(II) complex, (Ph2Pmorph)2PdCl2.A phosphine-benzaldimine, Ph2P(CH2)3NC(H)C6H5, has been obtained by reacting Ph2P(CH2)3NH2, from the reduction of PhP(CH2)2CN, with benzaldehyde in the presence of molecular sieves.
- Blinn, D.A.,Button, R.S.,Farazi, V.,Neeb, M.K.,Tapley, C.L.,et al.
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p. 143 - 152
(2007/10/02)
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- A Skeletal Rearrangement of γ-(Acyloxy)-β-keto Phosphonates: Studies on the Formation of 2(3H)-Furanones
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When treated with sodium hydride in dimethoxyethane, some γ-(acyloxy)-β-keto phosphonates react to give 2(3H)-furanones via an unexpected rearrangement which proceeds with carbon-carbon bond formation.Several possible mechanisms for this transformation have been tested through crossover experiments, rearrangement of an isotopically labeled substrate, and synthesis of a model intermediate.Results from these experiments allow elimination of several potential reaction pathways from further consideration and suggest a focus for future studies.
- Roussis, Vassilios,Gloer, Katherine B.,Wiemer, David F.
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p. 2011 - 2015
(2007/10/02)
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