- Vascular endothelial growth factor receptor inhibitor and preparation method and application thereof
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The invention provides a vascular endothelial growth factor receptor inhibitor and a preparation method and application thereof, and relates to a quinoline or quinazoline derivative with a structure as shown in a formula (I), a pharmaceutical composition containing a compound as shown in the formula (I) and application of the compound in preparation of drugs for preventing or treating angiogenesis-related diseases, in particular to prevention or treatment of tumors related to protein tyrosine kinase. Each substituent in the formula (I) is the same as the definition in the specification.
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Paragraph 0072; 0076-0077
(2020/12/14)
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- Discovery of N-aryl-9-oxo-9H-fluorene-1-carboxamides as a new series of apoptosis inducers using a cell- and caspase-based high-throughput screening assay. 2. Structure-activity relationships of the 9-oxo-9H-fluorene ring
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As a continuation of our studies of apoptosis inducing 9-oxo-9H-fluorene-1-carboxamides as potential anticancer agents, we explored modification of the 9-oxo-9H-fluorene ring. SAR studies showed that most changes to the 9-oxo-9H-fluorene ring were not wel
- Kemnitzer, William,Sirisoma, Nilantha,Jiang, Songchun,Kasibhatla, Shailaja,Crogan-Grundy, Candace,Tseng, Ben,Drewe, John,Cai, Sui Xiong
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scheme or table
p. 1288 - 1292
(2010/06/15)
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- NOVEL COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS AND USES THEREOF
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The present invention relates to compounds of formula (I), or pharmaceutical salts, prodrugs, salts of prodrugs, or combinations thereof, formula (I). wherein R1, R2, R3, R4, and L1 are defined in the specfication, compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and compositions. The present invention also relates to compounds of formula (II), or pharmaceutical salts, prodrugs, salts of prodrugs, or combinations thereof, formula (II). wherein R1a, R2a, Rx, and n are as defined in the specification, compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and compositions.
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Page/Page column 94
(2009/06/27)
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- NOVEL COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS AND USES THEREOF
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The present invention relates to compounds of formula (I), or pharmaceutical salts, prodrugs, salts of prodrugs, or combinations thereof, wherein R1, R2, R3, and L1 are defined in the specfication, compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and compositions. The present invention also relates to compounds of formula (II), or pharmaceutical salts, prodrugs, salts of prodrugs, or combinations thereof, wherein R1a, R2a and (Rx)n are as defined in the specification, compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and compositions.
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Page/Page column 35
(2008/06/13)
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- SUBSTITUTED BENZOYLAMINO-INDAN-2-CARBOXYLIC ACIDS AND RELATED COMPOUNDS
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The present invention relates to A compound of the formula Ia wherein in any of its stereoisomers forms or a mixture of stereoisomeric forms in any ratio, or a physiologically acceptable salt thereof, wherein the substituents are as described herein. The inventive compounds have CXCR5 inhibitory activity are particularly useful in treating or preventing various inflammatory diseases, such as rheumatoid arthritis, multiple sclerosis, lupus, Crohn's Disease, associated with the modulation of the human CXCR5 receptor.
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Page/Page column 67-68
(2009/01/24)
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- SUBSTITUTED N-ARYL-9-OXO-9H-FLUORENE-1-CARBOXAMIDES AND ANALOGS AS ACTIVATOR OF CASPASES AND INDUCERS OF APOPTOSIS
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The present invention is directed to substituted N-aryl-9-oxo-9H-fluorene-1-carboxamides and analogs thereof, represented by the general Formula I: (I) wherein R1-R8, X and Ar are defined herein. The present invention also relates to the discovery that co
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Page/Page column 41
(2010/10/20)
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- Quaternary ammonium compounds as tachykinin antagonists
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The present invention provides a compound of formula (I) wherein R is phenyl, C3-C7cycloalkyl or heteroaryl, each of which being optionally benzo- or C3-C7cycloalkyl-fused and optionally substituted, including in the benzo- or C3-C7cycloalkyl-fused portion, by from 1 to 3 substituents each independently selected from C1-C4alkyl, fluoro(C1-C4)alkyl, C1-C4alkoxy, fluoro(C1-C4)alkoxy, phenoxy, C2-C4alkanoyl, halo, C1-C4alkoxycarbonyl, C3-C7cycloalkyl, —S(O)m(C1-C4alkyl), cyano, —NR2R3, —S(O)mNR2R3, —NR4(C1-C4alkanoyl) and —CONR2R3, or R is 2,3-dihydrobenzo[b]furanyl or chromanyl; R1is H or C1-C6alkyl; W is a direct link, methylene or ethylene; X is unbranched C2-C4alkylene; Y is phenyl, naphthyl, benzyl, pyridyl, thienyl or C3-C7cycloalkyl, each of which being optionally substituted by from 1 to 3 substituents each independently selected from C1-C4alkyl, fluoro(C1-C4)alkyl, C1-C4alkoxy, fluoro(C1-C4)alkoxy, halo and cyano; Ar is phenyl, naphthyl, benzyl, thienyl, benzo[b]thienyl or indolyl, each of which being optionally substituted by from 1 to 3 substituents each independently selected from C1-C4alkyl, fluoro(C1-C4)alkyl, C1-C4alkoxy, fluoro(C1-C4)alkoxy, halo and cyano, or Ar is 1,3-benzodioxolan-4 or 5-yl or 1,4-benzodioxan-5 or 6-yl; ZAis a pharmaceutically acceptable anion; with the proviso that when W is a direct link and R is optionally fused and optionally substituted heteroaryl, said heteroaryl is linked by a ring carbon atom to the carbonyl group. The compounds are tachykinin antagonists.
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- Synthesis and phosphodiesterase 5 inhibitory activity of novel phenyl ring modified sildenafil analogues
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New sildenafil analogues containing an ether ring fused into the phenyl moiety, 6a-d and 7a-d, were efficiently synthesized from the readily available starting materials, 1a-d and 2, in five steps. Ab initio calculations indicated that introduction of a cyclic ether to the phenyl group might enhance the co-planarity of the molecule. The torsional angles were calculated to be 2-3° for the 5-membered cyclic ether derivatives, 6a, 6c, 7a, and 7c, and 12-16° for the 6-membered ones, 6b, 6d, 7b, and 7d. On the other hand, sildenafil showed the least co-planarity with the torsional angle of 23° compared with the target compounds, 6a-d and 7a-d. in the enzyme assay, however, the in vitro PDE 5 inhibitory activity was found out to be inversely related to the degree of co-planarity. In other words, the least planar sildenafil showed the highest actiivty, and the most planar 5-membered cyclic ether derivatives were least active by 100-200-fold compared with sildenafil. Our study clearly demonstrated that the open chain 2'-alkoxy group of the phenyl ring, although less effective for inducing the co-planarity, seemed to act as a much better lipophilic requirement than the cyclic alkoxy moiety. Copyright
- Kim, Dae-Kee,Lee, Namkyu,Lee, Ju Young,Ryu, Do Hyun,Kim, Jae-Sun,Lee, Suk-Ho,Choi, Jin-Young,Chang, Kieyoung,Kim, Young-Woo,Im, Guang-Jin,Choi, Won-Son,Kim, Tae-Kon,Ryu, Je-Ho,Kim, Nam-Ho,Lee, Kyoungrim
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p. 1609 - 1616
(2007/10/03)
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- Synthesis and properties of Biagra [1]. A 5-(2,3-dihydro-7-benzofuryl) analog of Viagra
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The synthesis and spectral properties (IR, MS, NMR) of a substituted 5-(2,3-dihydro-7-benzofuryl)pyrazolo[4,3-d]pyrimidin-7-one (2), an analog of Viagra (1), are described. The generally applicable route involves interaction of 2,3-dihydro-7-benzofuranoyl chloride (3) with 4-amino-1-methyl-3-propyl-5-pyrazolecarboxamide (4), and the resulting bis-amide (5) is cyclized to the corresponding substituted pyrazolo[4,3-d]pyrimidin-7-one (6). Chlorosulfonylation of 6, followed by treatment with 1-methylpiperazine, furnished the title compound 2 (named Biagra). Preliminary experiments "associated with the erectile process" on rats lend evidence of greater potency of Biagra (2) as compared to Viagra (1).
- Voelter, Wolfgang,El-Abadelah, Mustafa M.,Sabri, Salim S.,Khanfar, Monther A.
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p. 1469 - 1473
(2007/10/03)
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- Synthesis of new 7-benzofuranmethanamines as heterocyclic analogues of the squalenepoxidase-inhibitor Butenafine
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Selected title compounds (6a-f, 7a-d) were synthesized by RedAl(R)-reduction of the carboxamides 4a-f and 5a-d, easily available from the corresponding (2,3-dihydro-)7-benzofurancarboxylic acids 1a-f or 2a-d, respectively. For practical reasons, the preparation of the 2,3-dihydro-2-methyl-7-benzofuranmethanamines 6h-k with varied N-substitution by alkylation of the N-methyl-benzofuranmethanamine 6g with preformed aralkylbromides 9a-d was preferred.
- Stanetty,Koller,Purstinger,Grubner
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p. 351 - 358
(2007/10/02)
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- Zatosetron, a Potent, Selective, and Long-Acting 5HT3 Receptor Antagonist: Synthesis and Structure-Activity Relationships
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Antagonists of 5HT3 receptors are clinically effective in treating nausea and emesis associated with certain oncolytic drugs, including cisplatin.Moreover, these agents may be useful in pharmacological management of several central nervous system disorders, including anxiety, schizophrenia, dementia, and substance abuse.Our studies on aroyltropanamides led to the discovery that dihydrobenzofuranyl esters and amides are potent 5HT3 receptor antagonists.Simple benzoyl derivatives of tropine and 3α-aminotropane possessed weak 5HT3 receptor antagonist activity, as judged by blockade of bradycardia produced by iv injection of serotonin (5HT) to anesthetized rats.Within this series, use of benzofuran-7-carboxamide as the aroyl moiety led to a substantial increase of 5HT3 receptor affinity.The optimal 5HT3 receptor antagonist identified via extensive SAR studies was endo-5-chloro-2,3-dihydro-2,2-dimethyl-N-(8-methyl-8-azabicyclooct-3-yl)-7-benzofurancarboxamide (Z)-2-butenedioate (zatosetron maleate).The 7-carbamyl regiochemistry, dimethyl substitution, chloro substituent, and endo stereochemistry were all crucial elements of the SAR.Zatosetron maleate was a potent antagonist of 5HT-induced bradycardia in rats (ED50=0.86 μg/kg iv).Low oral doses of zatosetron (30 μg/kg) produced long-lasting antagonism of 5HT3 receptors, as evidenced by blockade of 5HT-induced bradycardia for longer than 6 h in rats.Moreover, this compound did not produce hemodynamic effects after iv administration to rats, nor did it block carbamylcholine-induced bradycardia in doses that markedly blocked 5HT3 receptors.Thus, zatosetron is a potent, selective, orally effective 5HT3 receptor antagonist with a long duration of action in rats.
- Robertson, David W.,Lacefield, William B.,Bloomquist, William,Pfeifer, William,Simon, Richard L.,Cohen, Marlene L.
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p. 310 - 319
(2007/10/02)
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- Synthesis and characterization of iodobenzamide analogues: Potential D-2 dopamine receptor imaging agents
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(S)-N-[(1-Ethyl-2-pyrrolidinyl)methyl]-2-hydroxy-3-iodo-6-methoxybenza mide ([123I]IBZM) is a central nervous system (CNS) D-2 dopamine receptor imaging agent. In order to investigate the versatility of this parent structure in specific dopamine receptor localization and the potential for developing new dopamine receptor imaging agents, a series of new iodinated benzamides with fused ring systems, naphthalene (INAP) and benzofuran (IBF), was synthesized and radiolabeled, and the in vivo and in vitro biological properties were characterized. The best analogue of IBZM is IBF (21). The specific binding of [125I]IBF (21) with rat striatal tissue preparation was found to be saturable and displayed a K(d) of 0.106 ± 0.015 nM. Competition data of various receptor ligands (for [125I]IBF (21) binding show the following rank order of potency: spiperone > IBF (21) > IBZM > (+)-butaclamol > (±)-ADTN,6,7 > ketanserin > SCH-23390 >> propranolol. The in vivo biodistribution results confirm that [125I]IBF (21) concentrated in the striatal area after iv injection into rats. The study demonstrates that [123I]IBF (21) is a potential agent for imaging CNS D-2 dopamine receptors.
- Murphy,Kung,Kung,Billings
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p. 171 - 178
(2007/10/02)
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