3554-65-2Relevant academic research and scientific papers
FUMAGILLOL COMPOUNDS AND METHODS OF MAKING AND USING SAME
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, (2018/03/06)
Disclosed herein, in part, are fumagillol compounds and methods of use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of making fumagillol compounds are provided. The compounds are contemplated to have activity against methionyl aminopeptidase 2.
6-AMINO QUINAZOLINE OR 3-CYANO QUINOLINE DERIVATIVES, PREPARATION PROCESS AND PHARMACEUTICAL USE THEREOF
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Page/Page column 44; 45, (2016/10/08)
The present disclosure relates to 6-amino quinazoline or 3-cyano quinoline derivatives, preparation processes and pharmaceutical compositions containing them. Specifically, the present disclosure relates to novel 6-amino quinazoline or 3-cyano quinoline derivatives presented by formula (I), or its tautomer, enantiomer, diastereomer, racemate or pharmaceutically acceptable salts thereof, or metabolite, metabolic precursor or prodrug thereof, and the uses for treatment especially for protein kinase inhibitors, in which each substitute group of general formula (I) is as defined in the specification.
PHARMACEUTICALLY ACCEPTABLE SALT OF (E)-N-[4-[[3-CHLORO-4-(2-PYRIDYLMETHOXY)PHENYL]AMINO]-3-CYANO-7-ETHOXY-6-QUINOLYL]-3-[(2R)-1-METHYLPYRROLIDIN-2-YL]PROP-2-ENAMIDE, PREPARATION METHOD THEREFOR, AND MEDICAL USE THEREOF
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Page/Page column 0032; 0033, (2014/01/23)
Provided as represented by formula (I) is a pharmaceutically acceptable salt of (E)-N-[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl] -3-[(2R)-1-methylpyrrolidin-2-yl]prop-2-enamide, a preparation method therefor, and a use thereof as a therapeutic agent and especially as a protein kinase inhibitor.
PHARMACEUTICALLY ACCEPTABLE SALT OF (E)-N-[4-[[3-CHLORO-4-(2-PYRIDYLMETHOXY)PHENYL]AMINO]-3-CYANO-7-ETHOXY-6-QUINOLYL]-3-[(2R)-1-METHYLPYRROLIDIN-2-YL]PROP-2-ENAMIDE, PREPARATION METHOD THEREOF, AND MEDICAL USE THEREOF
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Paragraph 0037; 0038, (2014/02/15)
Provided as represented by formula (I) is a pharmaceutically acceptable salt of (E)-N-[4-[[3-chloro-4-(2-pyridylmethoxy)phenyl]amino]-3-cyano-7-ethoxy-6-quinolyl]-3-[(2R)-1-methylpyrrolidin-2-yl]prop-2-enamide, a preparation method thereof, and a use thereof as a therapeutic agent, and especially as a protein kinase inhibitor.
6-AMINO QUINAZOLINE OR 3-CYANO QUINOLINE DERIVATIVES, PREPARATION METHODS AND PHARMACEUTICAL USES THEREOF
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, (2012/07/13)
6-amino quinazoline or 3-cyano quinoline derivatives, preparation methods and pharmaceutical uses thereof are disclosed. Specifically, the present disclosure discloses novel 6-amino quinazoline or 3-cyano quinoline derivatives presented by general formula (I), or tautomers, enantiomers, diastereomers, racemates or pharmaceutically acceptable salts thereof, or metabolites, metabolic precursors or prodrugs thereof, and their uses as treatment agents especially as protein kinase inhibitors, in which each substitutent group of general formula (I) is as defined in the specification.
IMIDAZO [1, 2 - B] PYRIDAZINE DERIVATIVES AS CDPK1 INHIBITORS
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Page/Page column 101, (2012/10/08)
A first aspect of the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or ester thereof, (Formula (I)) wherein: R1 is -(CH2)nNR3R4, -OR5 or -(CH2)n-heterocycloalkyl, wherein said heterocycloalkyl group is optionally substituted by one or more R7 groups; R2 is selected from aryl, heteroaryl, fused aryl-heterocycloalkyl and fused hetero aryl-heterocycloalkyl each of which is substituted by at least one R8 group; R3 is H or alkyl; R4 is: (i) cycloalkyl optionally substituted by one or more -NR11R12 or NHCOR11 groups; or (ii) -(CH2)n-heterocycloalkyl, wherein said heterocycloalkyl is a 4, 5 or 6-membered nitrogen-containing group optionally containing one or more CO groups, wherein said heterocycloalkyl is optionally substituted by one or more one or more (CH2)nR7 groups; or (iii) alkyl substituted by one or more -NR11R12groups; or R3 and R4 are linked together with the nitrogen to which they are attached to form a 4, 5, 6 or 7-membered monocyclic heterocycloalkyl group or a bicyclic heterocyclic group, each of which optionally contains one or two further groups selected from CO, O, N and S, and which is optionally further substituted by one or more R7 groups; R5 is selected from alkyl, -(CH2)n-heteroaryl and - (CH2)n-heterocycloalkyl, wherein said heteroaryl and heterocycloalkyl groups are each optionally substituted by one or more R7 groups; each R8 is independently selected from - NR16R17, -OR17 and -(CH2)nR17 where each R16 is H and each R17 is independently - (CHR10)n-heteroaryl, wherein said heteroaryl group is in turn optionally substituted by one or more R7 groups; each R10, R11 and R12 is independently H or alkyl; or in the case of an - NR11R12 group, R11 and R12 may be linked together with the nitrogen to which they are attached to form a 4, 5, 6 or 7-membered monocyclic or bicyclic heterocycloalkyl group optionally containing one or two further groups selected from CO, O, N and S, and which is optionally further substituted by one or more R7 groups; each m is independently an integer from 1 to 6; and each n is independently an integer from 0 to 6. Further aspects relate to the use of said compounds in the treatment of various therapeutic disorders, and more particularly as inhibitors of PfCDPK1.
QUATERNARY AMMONIUM SALTS AS M3 ANTAGONISTS
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Page/Page column 38-39, (2008/06/13)
Compounds of formula (I), in salt or zwitterionic form, wherein J, L, M, R1, R2, R3, R4 and R5 have the meanings as indicated in the specification, are useful for treating conditions that are mediated by the muscarinic M3 receptor. Pharmaceutical compositions that contain the compounds and a process for preparing the compounds are also described.
Enantioselective, facially selective carbomagnesation of cyclopropenes
Liu, Xiaozhong,Fox, Joseph M.
, p. 5600 - 5601 (2007/10/03)
Described is the facially selective and enantioselective addition of carbon nucleophiles to prochiral 3-hydroxymethylcyclopropenes. The process creates up to four stereocenters in a tandem addition/capture sequence that combines three simple materials to give complex and diverse products. The asymmetry is induced by the inexpensive and recoverable ligand (S)-N-methylprolinol. The enantioselectivity (90-98% ee with MeMgCl) is high for a range of cyclopropenes and electrophiles. Importantly, the diastereoselectivity is complementary to that obtained by enantioselective cyclopropanation with aryldiazoacetates. High enantioselectivities are obtained only when methoxide is included in the reaction. Evidence is provided that at least two chiral ligands are involved in the enantioselectivity-determining step. Copyright
Analogues of carbacholine: Synthesis and relationship between structure and affinity for muscarinic and nicotinic acetylcholine receptors
Sokilde, Birgitte,Mikkelsen, Ivan,Stensbol, Tine B.,Andersen, Birgit,Ebdrup, Soren,Krogsgaard-Larsen, Povl,Falch, Erik
, p. 95 - 104 (2007/10/02)
A series of acyclic and heterocyclic analogues of carbacholine (1) was synthesized using N-methylcarbacholine (MCC, 2), N,N-dimethylcarbacholine (DMCC, 3), and the corresponding tertiary amine (4) as leads. Whereas nicotinic acetylcholine receptor affinity was determined using [3H]nicotine as the radioactive ligand, [3H]oxotremorine-M ([3H]Oxo-M) and [3H]quinuclidinyl benzilate ([3H]QNB), in some cases supplemented with [3H]pirenzepine ([3H]PZ), were used as radioligands for muscarinic acetylcholine receptors on rat brain membranes. On the basis of receptor binding data, nicotinic/muscarinic (N/M) selectivity factors were determined, and muscarinic receptor efficacy (M agonist index) and M1 selectivity (M2/M1 index) estimated. In most cases, quaternized analogues showed higher affinity than the corresponding tertiary amines for muscarinic and, in particular, nicotinic receptor sites. Among the new compounds, N,N-diethylcarbacholine (9e) (IC50 = 0.046 μM), (S)-1-methyl-2-(N,N-dimethylaminocarbonyloxymethyl)pyrrolidine (17k) (IC50 = 0.068 μM), and the corresponding quaternized analogue, 18k (IC50 = 0.018 μM) showed the highest nicotinic receptor affinity. The tertiary amine, 17k showed much higher nicotinic receptor affinity than the acyclic analogue, 4 (IC50 = 5.7 μM), and the N/M selectivity factor determined for 17k (150) is an order of magnitude lower than that of nicotine (1400). The N/M selectivity factors for MCC (2) and DMCC (3), previously reported to be highly selective nicotinic receptor ligands, were shown to be 6.5 and 60, respectively, the latter value being comparable with that of 18k (89).
Alkylation of 2-Lithio-N-Methylpiperidines and -pyrrolidines: Scope, Limitations, and Stereochemistry
Gawley, Robert E.,Zhang, Qianhui
, p. 5763 - 5769 (2007/10/03)
The scope and limitations of the alkylation of racemic and nonracemic 2-lithipiperidines and -pyrrolidines, obtained by transmetalation of the corresponding stannanes, is reported.These organolithiums react with a variety of electrophiles to afford 2-substituted pyrrolidines and piperidines in excellent yield.With primary alkyl halides the reaction proceeds with net inversion of configuration at the metal-bearing carbon in the piperidines; in the pyrrolidines there is a mixture of inversion and retention, with the former predominating.With most carbonyl electrophiles (carbon dioxide, dimethyl carbonate, methyl chloroformate, pivaloyl chloride, benzaldehyde, and dialkyl ketones), retention is observed in both cases.Electrophiles such as benzophenone, benzyl bromide, and tert-butyl bromoacetate afford racemic coupling products.A mechanistic interpretation is presented.
