- Synthesis and Antiproliferative Activities of Novel Substituted 5-Anilino-α-Glucofuranose Derivatives
-
In order to find novel antitumor candidate agents with high efficiency and low toxicity, 14 novel substituted 5-anilino-α-glucofuranose derivatives have been designed, synthesized and evaluated for antiproliferative activities in vitro. Their structures were characterized by NMR (1H and 13C) and HR-MS, and configuration (R/S) at C(5) was identified by two-dimensional 1H,1H-NOESY-NMR spectrum. Their antiproliferative activities against human tumor cells were investigated by MTT assay. The results demonstrated that most of the synthesized compounds had antiproliferative effects comparable to the reference drugs gefitinib and lapatinib. In particular, (5R)-5-O-(3-chloro-4-{[5-(4-fluorophenyl)thiophen-2-yl]methyl}anilino)-5-deoxy-1,2-O-(1-methylethylidene)-α-glucofuranose (9da) showed the most potent antiproliferative effects against SW480, A431 and A549 cells, with IC50 values of 8.57, 5.15 and 15.24 μm, respectively. This work suggested 5-anilino-α-glucofuranose as an antitumor core structure that may open a new way to develop more potent anti-cancer agents.
- Hou, Qiaoli,Li, Baolin,Li, Xiabing,Sun, Baoli,Wang, Lili,Wang, Wei,Zhang, Yaling
-
-
- Design, synthesis and biological evaluation of novel 7H-benzo [c] [1, 3] dioxolo [4, 5-f] chromen-7-one derivatives with potential anti-tumor activity
-
In this study, a series of novel 7H-benzo [c] [1,3] dioxolo [4, 5-f] chromen-7-one derivatives were obtained by structural modification of the lead compounds with Fissitungfine B. A total 15 compounds were designed, synthesized and evaluated as inhibitors of tumor. These target compounds have the novel chemical structures that named three six-membered rings including one lactone six-membered ring. In vitro assay, the results showed that the target compounds have a broad spectrum and strong of anti-tumor activity. Such as the target compound 4n to MCF-7 was IC50 = 0.35 ± 0.01 μM, to A-549 was IC50 = 0.37 ± 0.01 μM, to Hela was IC50 = 0.56 ± 0.02 μM, to MDC-803 was IC50 = 0.53 ± 0.02 μM and COLO-205 was IC50 = 0.50 ± 0.02 μM in vitro. At the same time, in vivo anti-tumor activity assay results showed that the target compounds had a good inhibitory effect on tumor growth. Among them, the target compound 4n had the best anti-tumor activity, it could inhibit tumor growth well at a low dose. The target compound 4n could be used as a candidate drug for further research and development, in order to be used as early as application in the clinical treatment of tumors.
- Zhou, Shiyang,Huang, Gangliang
-
-
- Design and synthesis of arylamidine derivatives as serotonin/norepinephrine dual reuptake inhibitors
-
To improve the in vivo antidepressant activity of previously reported serotonin (5-HT) and norepinephrine (NE) dual reuptake inhibitors, three series of arylamidine derivatives were designed and synthesized. The in vitro 5-HT and NE reuptake inhibitory activities of these compounds were evaluated, and compound II-5 was identified as the most potent 5-HT (IC50 = 620 nM) and NE (IC50 = 10 nM) dual reuptake inhibitor. Compound II-5 exhibited potent antidepressant activity in the rat tail suspension test and showed an acceptable safety profile in a preliminary acute toxicity test in mice. Our results show that these arylamidine derivatives exhibit potent 5-HT/NE dual reuptake inhibition and should be explored further as antidepressant drug candidates.
- Wen, Hui,Qin, Wen,Yang, Guangzhong,Guo, Yanshen
-
-
- Heterocyclic Compounds and Methods of Use
-
This disclosure provides compounds and methods of using those compounds to treat liver fibrosis, including liver fibrosis which is a precursor to, is concurrent with, is associated with, or is secondary to nonalcoholic steatohepatitis (NASH); elevated cholesterol levels, and insulin resistance.
- -
-
Paragraph 0431; 0471; 0475
(2018/03/01)
-
- Diarylamino glucosan derivative, and preparation method and anti-tumor purpose thereof
-
The invention belongs to the field of medicinal chemistry, and particularly relates to a diarylamino glucosan derivative, and a preparation method and an anti-tumor purpose thereof, wherein the diarylamino glucosan derivative particularly relates to a compound shown as a formula I. The invention also relates to the preparation method of the diarylamino glucosan derivative, and the purpose of the diarylamino glucosan derivative in an aspect of preparing medicine for treating tumor diseases. The diarylamino glucosan derivative particularly has the obvious inhibition effects on human skin quamous cell carcinoma cells, human lung carcinoma cells and human colon cancer cells.
- -
-
Paragraph 0108; 0109; 0110; 0111; 0122; 0133
(2017/04/26)
-
- 2-Halobenzoyl chlorides in the synthesis of [1,3,4]thiadiazolo[3,2-a]quinazolin-5-one derivatives
-
New nitro and sulfonamide derivatives of [1,3,4]thiadiazolo[3,2-a]quinazolin-5-one have been synthesized by cyclocondensation of 1,3,4-thiadiazol-2-amines with 2-halobenzoyl chlorides containing electron-withdrawing substituents in positions 3, 4, and 5. An improved procedure has been proposed for the preparation of intermediate 2-fluoro-N-(5-methyl-1,3,4-thiadiazol-2-yl)benzamides containing a sulfamoyl group in the 5-position via selective acylation of 5-methyl-1,3,4-thiadiazol-2-amine with 5-chlorosulfonyl-2-fluorobenzoyl chloride, followed by sulfonylation of amines.
- Shlenev,Tarasov,Filimonov,Agat’ev,Danilova,Suponitskii, K. Yu.
-
p. 1870 - 1877
(2018/02/06)
-
- HETEROCYCLIC COMPOUNDS AND METHODS OF USE
-
This disclosure provides compounds and methods of using those compounds to treat metabolic disorders and hyperproliferative disorders, including administration of the compounds in conjunction with hormone receptor antagonists. Compounds of the invention may also find use in treating cancer. Presented herein are novel compounds bearing a perhaloalkylsulfonamide moiety. Such compounds, in addition to being highly effective SREBP inhibitors, are also unexpectedly highly bioavailable in vivo. Heteroaromatic compounds bearing sulfonamide groups are prone to several ionic states, based on the inherent pKa values.
- -
-
Paragraph 0145; 0188
(2015/03/16)
-
- HETEROCYCLIC COMPOUNDS AND METHODS OF USE
-
This disclosure provides compounds and methods of using those compounds to treat metabolic disorders and hyperproliferative disorders, including administration of the compounds in conjunction with hormone receptor antagonists.
- -
-
Paragraph 0407
(2015/03/16)
-
- Lowering the pKa of a bisimidazoline lead with halogen atoms results in improved activity and selectivity against Trypanosoma brucei in vitro
-
Diphenyl-based bis(2-iminoimidazolidines) are promising antiprotozoal agents that are curative in mouse models of stage 1 trypanosomiasis but devoid of activity in the late-stage disease, possibly due to poor brain penetration caused by their dicationic nature. We present here a strategy consisting in reducing the pKa of the basic 2-iminoimidazolidine groups though the introduction of chlorophenyl, fluorophenyl and pyridyl ring in the structure of the trypanocidal lead 4-(imidazolidin-2-ylideneamino)-N-(4-(imidazolidin-2-ylideneamino)phenyl)benzamide (1). The new compounds showed reduced pKa values (in the range 1-3 pKa units) for the imidazolidine group linked to the substituted phenyl ring. In vitro activities (EC50) against wild type and resistant strains of T. b. brucei (s427 and B48, respectively) were in the submicromolar range with four compounds being more active and selective than 1 (SI > 340). In particular, the two most potent compounds (3b and 5a) acted approximately 6-times faster than 1 to kill trypanosomes in vitro. No cross-resistance with the diamidine and melaminophenyl class of trypanocides was observed indicating that these compounds represent interesting leads for further in vivo studies.
- Ríos Martínez, Carlos H.,Nué Martínez, J. Jonathan,Ebiloma, Godwin U.,De Koning, Harry P.,Alkorta, Ibon,Dardonville, Christophe
-
p. 806 - 817
(2015/08/06)
-
- Structure-activity relationships for lipoprotein lipase agonists that lower plasma triglycerides in vivo
-
The risk of cardiovascular events increases in individuals with elevated plasma triglyceride (TG) levels, therefore advocating the need for efficient TG-lowering drugs. In the blood circulation, TG levels are regulated by lipoprotein lipase (LPL), an unstable enzyme that is only active as a non-covalently associated homodimer. We recently reported on a N-phenylphthalimide derivative (1) that stabilizes LPL in vitro, and moderately lowers triglycerides in vivo (Biochem. Biophys. Res. Commun. 2014, 450, 1063). Herein, we establish structure-activity relationships of 51 N-phenylphthalimide analogs of the screening hit 1. In vitro evaluation highlighted that modifications on the phthalimide moiety were not tolerated and that lipophilic substituents on the central phenyl ring were functionally essential. The substitution pattern on the central phenyl ring also proved important to stabilize LPL. However, in vitro testing demonstrated rapid degradation of the phthalimide fragment in plasma which was addressed by replacing the phthalimide scaffold with other heterocyclic fragments. The in vitro potency was retained or improved and substance 80 proved stable in plasma and efficiently lowered plasma TGs in vivo.
- Caraballo, Rémi,Larsson, Mikael,Nilsson, Stefan K.,Ericsson, Madelene,Qian, Weixing,Tran, Nam Phuong Nguyen,Kindahl, Tomas,Svensson, Richard,Saar, Valeria,Artursson, Per,Olivecrona, Gunilla,Enquist, Per-Anders,Elofsson, Mikael
-
p. 191 - 209
(2015/09/15)
-
- An Improved, Scalable and Impurity-Free Process for Lixivaptan
-
An optimized synthetic method in high efficiency has been developed for the synthesis of lixivaptan from 2-nitrobenzyl bromide and pyrrole-2-carboxaldehyde. The byproducts among this procedure and an unknown impurity in crude product were investigated. The byproducts were speculated by 1H NMR or MS. The unknown impurity was characterized by 1H NMR, 13C NMR, and HRMS, confirming the structures as N-[3-chloro-4-(5H-pyrrolo[2,1-c][1,4]benzodiazepine-10(11H)-ylcarbonyl)phenyl]-N-(5-fluoro-2-methylbenzoyl)-5-fluoro-2-methylbenzamide. Afterwards, the impurity was synthesized to make comparisons. The target product lixivaptan was obtained with 47.6% overall yield and 99.93% purity. This cost-effective and environmentally friendly process is suitable for scale-up production.
- Mu, Shuai,Niu, Duan,Liu, Ying,Zhang, Dashuai,Liu, Dengke,Liu, Changxiao
-
p. 1608 - 1613
(2015/11/09)
-
- Hypervalent iodine(III)-mediated oxidative dearomatizing cyclization of arylamines
-
An oxidative dearomatizing cyclization of arylamines promoted by iodobenzene bis(trifluoroacetate) [PhI(CF3CO2) 2] has been explored, leading to a novel synthetic approach to functionalized spirocyclic building blocks containing the structurally unique dieniminium moiety. This unprecedented methodology, featuring oxidative dearomatization and carbon-carbon bond-forming cyclization, to some extent, not only expands the synthetic potential of hypervalent iodine chemistry, but also enriches the oxidation chemistry of arylamines.
- Jin, Cong-Yang,Du, Ji-Yuan,Zeng, Chao,Zhao, Xian-He,Cao, Ye-Xing,Zhang, Xiang-Zhi,Lu, Xin-Yun,Fan, Chun-An
-
supporting information
p. 2437 - 2444
(2014/09/17)
-
- 3H-1,2,4-Dithiazol-3-one compounds as novel potential affordable antitubercular agents
-
Small molecules with oxathiazol-2-one moiety were recently reported as potent inhibitors of Mycobacterium bovis var. bacilli Calmette-Guérin (BCG), among which HT1171 was the most potent and selective proteasome inhibitor. Herein we synthesized a series of novel compounds by bioisosteric replacement of the oxathiazol-2-one ring with 3H-1,2,4-dithiazol-3-one, and also fifteen 1,3,4-oxathiazol-2-one molecules in order for potency comparison and structure-activity relationship elucidation since their antibacterial effects on the virulent strains were not evaluated before. All the compounds were assessed for antitubercular activities on the virulent H37Rv strain by a serial dilution method. Among the tested compounds, 3H-1,2,4-dithiazol-3-one compound 4n was found to be the most active with a lowest MIC90 value of 1 μg/mL. Furthermore, the cytotoxicities of all the compounds against normal human liver cell line L02 were determined by an MTT method. Compound 4n displayed a lower inhibitory ratio than HT1171 at the concentration of 100 μM, indicating its better safety profile.
- Yang, Jianzhong,Pi, Weiyi,Xiong, Li,Ang, Wei,Yang, Tao,He, Jun,Liu, Yuanyuan,Chang, Ying,Ye, Weiwei,Wang, Zhenling,Luo, Youfu,Wei, Yuquan
-
supporting information
p. 1424 - 1427
(2013/03/14)
-
- Rh[III]-catalyzed C-H amidation using aroyloxycarbamates to give N-Boc protected arylamines
-
The Rh(III)-catalyzed amidation of C(sp2)-H bonds by the use of electron-deficient aroyloxycarbamates as efficient electrophilic amidation partners is reported. The reaction proceeded under mild conditions with broad functional group tolerance, and pyridine and O-methyl hydroxamic acids serve as efficient directing groups, giving access to valuable N-Boc protected arylamines (also Fmoc and Cbz). Preliminary mechanistic experiments are discussed.
- Grohmann, Christoph,Wang, Honggen,Glorius, Frank
-
supporting information
p. 3014 - 3017
(2013/07/26)
-
- Novel TypeII Fatty Acid Biosynthesis (FAS II) Inhibitors as Multistage Antimalarial Agents
-
Malaria is a potentially fatal disease caused by Plasmodium parasites and poses a major medical risk in large parts of the world. The development of new, affordable antimalarial drugs is of vital importance as there are increasing reports of resistance to the currently available therapeutics. In addition, most of the current drugs used for chemoprophylaxis merely act on parasites already replicating in the blood. At this point, a patient might already be suffering from the symptoms associated with the disease and could additionally be infectious to an Anopheles mosquito. These insects act as a vector, subsequently spreading the disease to other humans. In order to cure not only malaria but prevent transmission as well, a drug must target both the blood- and pre-erythrocytic liver stages of the parasite. P.falciparum (Pf) enoyl acyl carrier protein (ACP) reductase (ENR) is a key enzyme of plasmodial typeII fatty acid biosynthesis (FASII). It has been shown to be essential for liver-stage development of Plasmodium berghei and is therefore qualified as a target for true causal chemoprophylaxis. Using virtual screening based on two crystal structures of PfENR, we identified a structurally novel class of FAS inhibitors. Subsequent chemical optimization yielded two compounds that are effective against multiple stages of the malaria parasite. These two most promising derivatives were found to inhibit blood-stage parasite growth with IC50 values of 1.7 and 3.0μM and lead to a more prominent developmental attenuation of liver-stage parasites than the gold-standard drug, primaquine.
- Schrader, Florian C.,Glinca, Serghei,Sattler, Julia M.,Dahse, Hans-Martin,Afanador, Gustavo A.,Prigge, Sean T.,Lanzer, Michael,Mueller, Ann-Kristin,Klebe, Gerhard,Schlitzer, Martin
-
p. 442 - 461
(2013/08/25)
-
- Discovery of phosphoric acid mono-{2-[(E/Z)-4-(3,3-dimethyl-butyrylamino)- 3,5-difluorobenzoylimino]-thiazol-3-ylmethyl} Ester (Lu AA47070): A phosphonooxymethylene prodrug of a potent and selective hA2A receptor antagonist
-
The discovery and structure-activity relationship of a series of hA 2A receptor antagonists is described. Compound 28 was selected from the series as a potent and selective compound and was shown to be efficacious in an in vivo model of Parkinson's disease. It had acceptableADME properties; however, the low intrinsic solubility of this compound was limiting for its developability, because the oral bioavailability from dosing in suspension was significantly lower than the oral bioavailability from solution dosage. As a consequence, prodrugs of 28 were prepared with dramatically increased aqueous solubility. The prodrugs efficiently delivered 28 into systemic circulation, with no detectable levels of prodrug in plasma samples. From this investigation, we selected 32 (Lu AA47070), a phosphonooxymethylene prodrug of 28, as a drug candidate.
- Sams, Anette G.,Mikkelsen, Gitte K.,Larsen, Mogens,Langg?rd, Morten,Howell?, Mark E.,Schr?der, Tenna J.,Brennum, Lise T.,Torup, Lars,J?rgensen, Erling B.,Bundgaard, Christoffer,Kreilg?rd, Mads,Bang-Andersen, Benny
-
supporting information; experimental part
p. 751 - 764
(2011/04/18)
-
- Synthesis of (2-chlorophenyl)(phenyl)methanones and 2-(2-chlorophenyl)-1- phenylethanones by Friedel-Crafts acylation of 2-chlorobenzoic acids and 2-(2-chlorophenyl)acetic acids using microwave heating
-
Several 2-(2-chlorophenyl)-1-phenylethanones and (2-chlorophenyl)(phenyl) methanones were prepared by the Friedel-Crafts acylation reaction of 2-(2-chlorophenyl) acetic acids and 2-chlorocarboxylic acids, respectively, in the presence of cyanuric chloride, pyridine, and AlCl3 or FeCl 3 using microwave heating. The yields of the ketones were significantly higher than those obtained using conventional heating. In addition, similar reactions carried out with the less inexpensive and less toxic FeCl3 gave titled ketones in comparable yields. Interestingly, the FeCl3 catalyzed reactions gave pure ketones (no chromatographic purification required), whereas the AlCl3 catalyzed reaction gave impure product that required chromatographic purification.
- Mahdi, Jasia,Ankati, Haribabu,Gregory, Jill,Tenner, Brian,Biehl, Edward R.
-
experimental part
p. 2594 - 2596
(2011/06/21)
-
- Synthesis of a novel pyrrolo[1,2-c][1.3]benzodiazepine analogue of VPA-985
-
The seven-step synthesis of a novel structural isomer of VPA-985, N-[3-chloro-4-(5H-pyrrolo[1,2-c][1.3]benzodiazepin-6(11H)-ylcarbonyl)phenyl] -5-fluoro-2-methylbenzamide, is described. (2-Aminophenyl)(1H-pyrrol-2-yl) methanone was converted with thiophosgene into (2-isothiocyanatophenyl)(1H- pyrrol-2-yl)methanone which was cyclised in the presence of base to 5-thioxo-5,6-dihydro-11H-pyrrolo[1,2-c][1.3]benzodiazepin-11-one. The latter underwent desulfurisation with Raney nickel followed by reduction with lithium aluminium hydride in the presence of aluminium trichloride and the resulting 6,11-dihydro-5H-pyrrolo[1,2-c][1.3]-benzodiazepine acylated with 2-chloro-4-nitrobenzoyl chloride to afford 6-(2-chloro-4-nitrobenzoyl)-6,11- dihydro-5H-pyrrolo[1,2-c][1.3]benzodiazepine. The nitro group in the latter compound was reduced with zinc and ammonium chloride to give the corresponding aniline derivative which was then acylated with 2-methyl-5-fluorobenzoyl chloride to provide the final product.
- Rotas, Georgios,Kimbaris, Athanasios,Varvounis, George
-
experimental part
p. 7805 - 7810
(2011/10/12)
-
- NOVEL ENANTIOMERICALLY PURE COMPOUNDS FOR THE TREATMENT OF PROLIFERATIVE DISORDERS
-
The present invention relates to an enantiomerically pure (+)-trans-enantiomer of a compound represented by the following formula (I): wherein R1, R2, R3, R4 and R9 are as defined in the specification; enantiomerically pure intermediates thereof, to processes for the preparation of the enantiomerically pure compound and its intermediates, and to a pharmaceutical composition comprising the enantiomerically pure compound. The compound of formula (I) is useful for the treatment of diseases or disorders mediated by the inhibition of cyclin dependant kinase, such as cancer.
- -
-
Page/Page column 20
(2010/08/03)
-
- Novel synthesis and characterization of some new-2-(R) phenyl- 4-(-4-bromo-2-fluoro benzylidene)-oxazol-5-ones
-
In the present study a series of some new 2-(substituted) phenyl- 4-(4-bromo-2-fluoro benz-ylidene)-oxazol-5-ones (2a-2j) were synthesized by the condensation of selected substituted benzoyl glycine (1a-1j) with 4-bromo-2-fluoro benzaldehyde in the presence of fused sodium acetate and acetic anhydride. The constitution of the newly synthesized compounds has been supported by their physical properties, elemental analysis, colour, m.p, IR spectral analysis data.
- Pareek, Alok K.,Joseph,Seth, Daya S.
-
experimental part
p. 1533 - 1536
(2011/10/12)
-
- MODULATORS OF MITOTIC KINASES
-
The invention relates to compounds of Formula (I), a prodrug, a polymorph, a tautomer, an enantiomer, a stereoisomer, a solvate, an N-oxide, or a pharmaceutically acceptable salt thereof: (formula should be inserted here) which have inhibitory effect on one or more protein kinases that are involved in cell mitosis.
- -
-
Page/Page column 53-54
(2008/12/07)
-
- FUSED HETEROCYCLIC COMPOUND
-
A compound of the formula: wherein ring'' A is a 7-membered or 8-membered nitrogen- containing ring optionally further substituted, ring B is an optionally substituted aryl group or an optionally substituted heteroaryl group, X1 is a group represented by -NR3-Y1-, -0-, -S-, -SO-, -SO2- or -CHR3- wherein R3 is a hydrogen atom or'' an optionally substituted aliphatic hydrocarbon group, or R3 may be bonded to the carbon atom of ring B to form an optionally substituted ring structure, and Y1 is a bond or an optionally substituted C1-4 alkylene, R1 is a hydrogen atom, or an optionally substituted group bonded via a carbon atom or a sulfur atom, the formula = shows a single bond or a double bond, when ===R2 is - R2, R2 is a hydrogen atom, or an optionally substituted group bonded via a carbon atom, a nitrogen atom, an oxygen atom or a sulfur atom, and when ===R2 is =R2, R2 is an oxo group, an optionally substituted alkylidene group, or an optionally, substituted imino group.
- -
-
Page/Page column 330-331
(2010/11/28)
-
- ENANTIOMERICALLY PURE FLAVONE DERIVATIVES FOR THE TREATMENT OF POLIFERATIVE DISORDERS AND PROCESSES FOR THEIR PREPARATION
-
The present invention relates to an enantiomerically pure (+)-trans-enantiomer of a compound represented by the following formula (I): wherein R1, R2, R3, R4 and R9 are as defined in the specification; enantiomerically pure intermediates thereof, to processes for the preparation of the enantiomerically pure compound and its intermediates, and to a pharmaceutical composition comprising the enantiomerically pure compound. The compound of formula (I) is useful for the treatment of diseases or disorders mediated by the inhibition of cyclin dependant kinase, such as cancer.
- -
-
Page/Page column 62-63; 96-97
(2008/06/13)
-
- Synthesis and Structure-Activity Relationship of Aminobenzophenones. A Novel Class of p38 MAP Kinase Inhibitors with High Antiinflammatory Activity
-
We wish to report the synthesis and structure-activity relationship (SAR) of a series of 4-aminobenzophenones, as a novel compound class with high antiinflammatory activity. Our initial lead, {4-[(2-aminophenyl)amino]phenyl}(phenyl)methanone (3), was systematically optimized and resulted in compounds that potently inhibited the release of the proinflammatory cytokines IL-1β and TNF-α in human peripheral blood mononuclear cells stimulated by LPS. One of the most potent compounds, among others, was {4-[(2-aminophenyl)amino]-2-chlorophenyl}(2-methylphenyl)methanone (45) with IC50 values of 14 and 6 nM for the inhibition of IL-1β and TNF-α, respectively. Furthermore, we found these types of compounds to be potent and selective p38 MAP kinase inhibitors, e.g. 45 had an IC50 value of 10 nM. Molecular modeling was used to rationalize our SAR data and to propose a model for the interaction of compound 45 with the p38 MAP kinase. The model involved a favorable hydrogen bond between the carbonyl group of the benzophenone and the NH of Met-109, positioning ring A in the hydrophobic pocket I of the enzyme. Good antiinflammatory effects were demonstrated in two murine models of dermatitis after topical application (oxazolone and TPA model).
- Ottosen, Erik Rytter,S?rensen, Morten Dahl,Bj?rkling, Fredrik,Skak-Nielsen, Tine,Fjording, Marianne Scheel,Aaes, Helle,Binderup, Lise
-
p. 5651 - 5662
(2007/10/03)
-
- 7-Chloro-5-hydroxy-1-[2-methyl-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5- tetrahydro-1H-1-benzazepine (OPC-41061): A potent, orally active nonpeptide arginine vasopressin V2 receptor antagonist
-
We previously reported a series of benzazepine derivatives as orally active nonpeptide arginine vasopressin (AVP) V2 receptor antagonists. After the lead structure OPC-31260 was structurally evaluated and optimized, the introduction of the 7-Cl moiety on the benzazepine and 2-CH3 on the aminobenzoyl moiety enhanced its oral activity. The new AVP-V2 selective antagonist OPC-41061 was determined to be a potent and orally active agent. Copyright (C) 1999 Elsevier Science Ltd.
- Kondo, Kazumi,Ogawa, Hidenori,Yamashita, Hiroshi,Miyamoto, Hisashi,Tanaka, Michinori,Nakaya, Kenji,Kitano, Kazuyoshi,Yamamura, Yoshitaka,Nakamura, Shigeki,Onogawa, Toshiyuki,Mori, Toyoki,Tominaga, Michiaki
-
p. 1743 - 1754
(2007/10/03)
-
- Aniline derivatives
-
The invention concerns aniline derivatives of formula I STR1 wherein m is 1, 2 or 3, n is 0, 1, 2 or 3, Q is phenyl or naphthyl or a 5- or 6-membered heteroaryl moiety containing 1, 2 or 3 heteroatoms selected from oxygen, nitrogen and sulfur, and X, R1 and R2 are defined in the claims; or pharmaceutical compositions containing them, and the methods of using the compounds as tyrosine kinase inhibitors and for the treatment of proliferative diseases such as cancer.
- -
-
-
- Substituted N-Cyanomethyl-2-halo-N-methylarenecarboxamides as Precursors of 1,4-Benzothiazepines
-
2-Halogeno substituted N-cyanomethyl-N-methylbenzamides 1a-1i were investigated in a correlation analysis by ir spectroscopy to determine the conformational behavior. Compound 1h gives 4-methyl-2-methylthio-8-nitro-5-oxo-4,5-dihydro-1,4-benzothiazepine-3- carbonitrile 3 by dithiocarboxylation procedure whereas 1b was not able to react to heterocyclic seven-membered ring system.
- Doelling, Wolfgang,Perjessy, Alexander,Schaller, Ingrid,Kolbe, Alfred
-
p. 225 - 229
(2007/10/03)
-
- TRICYCLIC THIENO-AZEPINE VASOPRESSIN ANTAGONISTS
-
This invention relates to new bicyclic non-peptide vasopressin antagonists which are useful in treating conditions where decreased vasopressin levels are desired, such as in congestive heart failure, in disease conditions with excess renal water reabsorption and in conditions with increased vascular resistance and coronary vasoconstriction.
- -
-
-
- Technetium-99m labeled p-aminohippuric acid analogues: renal function agents.
-
A number of p-aminohippuric acid analogues were synthesized in order to develop clinically useful 99mTc-labeled radiopharmaceuticals for evaluation of renal function measurements. Stable 99mTc-labeled complexes were formed at pH 5.7 using a Sn(II) reduction method with all derivatives. The newly synthesized complexes were screened utilizing biodistribution studies in small animals. All complexes were excreted via the GU tract within 60 min post iv administration, with no significant activity in GI tract and liver. The [99mTc]methyl-PAHIDA complex showed optimal biodistribution among these analogues. Further investigation is needed to determine if these derivatives may be used to replace [131I]o-iodohippuric acid for the evaluation of renal function.
- Zhang,Bhargava,Chun,Blaufox,Chervu
-
p. 829 - 832
(2007/10/02)
-
- 3-Chloro-4-cyanophenyl 4'-substituted benzoates
-
Disclosed are compounds of the formula: STR1 wherein R is an alkyl group having 1 to 8 carbon atoms and X is a dioxane, cyclohexane, or benzene ring. The compounds of the invention are suitable as liquid crystal materials in electrooptical displays. Specifically, when added to nematic liquid crystals, these compounds provide an increase in the positive dielectric anisotropy of the liquid crystal composition.
- -
-
-