cas 13067-19-1, 3',4'-METHYLENEDIOXYACETANILIDE

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Synthesis and biological evaluation of 10,11-methylenedioxy-14- azacamptothecin
10,11-Methylenedioxy-14-azacamptothecin, a potent analogue of the antitumor agent camptothecin (CPT), has been prepared via a key condensation between AB and DE ring precursors. The biological testing of this compound validated a strategy for modulation of the off-rate of camptothecin analogues from the topoisomerase-DNA-CPT ternary complex via structural modification.
Elban, Mark A.,Sun, Wenyue,Eisenhauer, Brian M.,Gao, Rong,Hecht, Sidney M.
p. 3513 - 3516
(2006)
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Synthesis and bio-evaluation of novel quinolino-stilbene derivatives as potential anticancer agents
A series of 25 novel quinolino-stilbene derivatives were designed, synthesized and evaluated for their potential as anticancer agents. Three of them not only displayed quite potent antiproliferative activity with IC50 values 50 values in the range of 4-10 μM, and the rest was moderately active or inactive. One of these viz. 3-[E-(4-fluorostyryl)]-2-chloroquinoline (compound 7B) caused substantial DNA damage and arrested cell cycle in S phase. Interestingly, 7B was very active against MDA-MB468 (IC50 = 0.12 μM), but not against other cell lines examined. Compound 3-[Z-(3-(trifluoromethyl)styryl)]-2-chloroquinoline (12A), the most effective against all cancer cell lines examined, caused prolonged cell cycle arrest at mitosis and eventually apoptosis. Data from an in vitro study showed that compound 12A inhibited microtubule polymerization in a similar fashion to nocodazole. Further study using in silico molecular modeling revealed that 12A causes the impediment of microtubule polymerization by binding to tubulin at the same cavity where podophyllotoxin binds.
Srivastava, Vandana,Lee, Hoyun
p. 7629 - 7640
(2015)
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Dehydrative Beckmann rearrangement and the following cascade reactions
The Beckmann rearrangement has been predominantly studied for the synthesis of amide and lactam. By strategically using the in situ generated Appel's salt or Mitsunobu's zwitterionic adduct as the dehydrating agent, a series of Beckmann rearrangement and following cascade reactions have been developed herein. The protocol allows the conversion of various ketoximes into amide, thioamide, tetrazole and imide products in modular procedures. The generality and tolerance of functionalities of this method have been demonstrated.
Liu, Yinghui,Wei, Yongjiao,Xie, Lan-Gui
supporting information

(2021/11/16)

A novel construction of acetamides from rhodium-catalyzed aminocarbonylation of DMC with nitro compounds
Dimethyl carbonate (DMC), an environment-friendly compound prepared from CO2, shows diverse reactivities. In this communication, an efficient procedure using DMC as both a C1 building block and solvent in the aminocarbonylation reaction with nitro compounds has been developed. W(CO)6acts both a CO source and a reductant here.
Bao, Zhi-Peng,Miao, Ren-Guan,Qi, Xinxin,Wu, Xiao-Feng
supporting information
p. 1955 - 1958
(2021/03/02)

Preparation method of acetamide compound
The invention discloses a preparation method of an acetamide compound, the preparation method comprises the following steps: reacting tetracarbonyl dichloride rhodium, 1, 3-bis (diphenylphosphine) propane, tungsten carbonyl, sodium phosphate, sodium iodide, water, a nitro compound and dimethyl carbonate at 120 DEG C for 24 hours, and after the reaction is completed, performing post-treatment to obtain the acetamide compound. According to the preparation method, dimethyl carbonate serves as a C1 source and also serves as a green solvent, operation is easy, reaction starting raw materials are low in price and easy to obtain, the tolerance range of substrate functional groups is wide, and reaction efficiency is high. Various acetamide compounds can be synthesized according to actual needs, so that the practicability of the method is widened while the operation is convenient.
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Paragraph 0035-0047; 0056-0059

(2021/05/19)

Sulfuryl Fluoride Mediated Synthesis of Amides and Amidines from Ketoximes via Beckmann Rearrangement
A metal-free and redox-neutral method for Beckmann rearrangement employing inexpensive and readily available SO2F2 gas is described. The reported transformation proceeds at ambient temperature and is compatible with a wide range of sterically and electronically diverse aromatic, heteroaromatic, aliphatic and lignin-like oximes providing amides in good to excellent yields. The reaction proceeds through the formation of an imidoyl fluoride intermediate that can also be used for the synthesis of amidines.
Gurjar, Jitendra,Fokin, Valery V.
supporting information
p. 10402 - 10405
(2020/07/25)

Visible-light-induced Beckmann rearrangement by organic photoredox catalysis
A facile and general strategy for efficient direct conversion of oximes to amides using an inexpensive organic photocatalyst and visible light is described. This radical Beckmann rearrangement can be performed under mild conditions. Various alkyl aryl ketoximes and diaryl ketoximes can be effectively converted into the corresponding amides in excellent yields.
Tang, Li,Wang, Zhi-Lv,Wan, Hai-Lan,He, Yan-Hong,Guan, Zhi
supporting information
p. 6182 - 6186
(2020/09/01)

An Electrochemical Beckmann Rearrangement: Traditional Reaction via Modern Radical Mechanism
Abstract: Electrosynthesis as a potential means of introducing heteroatoms into the carbon framework is rarely studied. Herein, the electrochemical Beckmann rearrangement, i. e. the direct electrolysis of ketoximes to amides, is presented for the first time. Using a constant current as the driving force, the reaction can be easily carried out under neutral conditions at room temperature. Based on a series of mechanistic studies, a novel radical Beckmann rearrangement mechanism is proposed. This electrochemical Beckmann rearrangement does not follow the trans-migration rule of the classical Beckmann rearrangement.
Tang, Li,Wang, Zhi-Lv,He, Yan-Hong,Guan, Zhi
p. 4929 - 4936
(2020/08/21)

A Novel Difluoroacetic Acid Derivatives Compound, and Composition Comprising the Same
The present invention relates to a novel difluoroacetic acid derivative compound and a composition for various uses containing the same, wherein the difluoroacetic acid derivative compound can not only act as an agonist activating one among PPARandalpha;, andbeta; or andgamma;, but also can exhibit double efficacy or triple efficacy. Therefore, the difluoroacetic acid derivative compound can more effectively prevent, alleviate or treat metabolic diseases in which PPARs involves, and further exhibits whitening and wrinkle alleviation activity, and anti-inflammatory and antioxidant effects, thereby being able to be usefully utilized as various compositions.COPYRIGHT KIPO 2020
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Paragraph 0086; 0292-0297

(2020/04/23)

CHEMICAL ENTITIES, PHARMACEUTICAL FORMULATIONS, AND METHODS FOR TREATING FIBROSIS
Disclosed herein are chemical entities, or pharmaceutically acceptable salts thereof, for treating fibrosis, including pulmonary fibrosis, such as idiopathic pulmonary fibrosis. Also disclosed herein are pharmaceutical formulations for treating fibrosis, the pharmaceutical formulations including one or more of the foregoing chemical entities and one or more pharmaceutically acceptable excipients, carriers, vehicles, or a combination thereof. Also disclosed herein are packaged pharmaceutical formulations for treating fibrosis, the packaged pharmaceutical formulations including one of the foregoing pharmaceutical formulations and instructions for using the pharmaceutical formulation to treat a patient having fibrosis or susceptible to fibrosis. Also disclosed herein is a method for treating fibrosis, the method including administering one of the foregoing pharmaceutical formulations.
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Paragraph 0091-0092

(2020/11/23)

Phenysilane and Silicon Tetraacetate: Versatile Promotors for Amide Synthesis
Phenylsilane was reevaluated as a useful coupling reagent for amide synthesis. At room temperature, a wide range of amides and peptides were obtained in good to excellent yields (up to 99 %). For the first time, Weinreb amides synthesis mediated by a hydrosilane were also documented. Comparative experiments with various acetoxysilanes suggested the involvement of a phenyl-triacyloxysilane. From this mechanistic study, silicon tetraacetate was shown as an efficient amine acylating agent.
Morisset, Eléonore,Chardon, Aurélien,Rouden, Jacques,Blanchet, Jér?me
supporting information
p. 388 - 392
(2020/01/24)

o-Phthalic Anhydride/Zn(OTf)2 co-catalyzed Beckmann rearrangement under mild conditions
o-Phthalic anhydride/Zn(OTf)2 co-catalyzed Beckmann rearrangement was developed, producing the corresponding amide in up to 99% yield with acid-sensitive functionalities tolerated well, and the scale of the reaction could be enlarged to 77 mmol and the excellent yield was maintained. A successive procedure was developed. Moreover, the reaction was carried out at rt under nearly neutral conditions, and the workup was concise. These features illustrated the potential of the protocol in amide synthesis.
Xu, Ze-Feng,Zhang, Teng,Hong, Wenjun
supporting information
p. 3113 - 3117
(2019/05/08)

Mild, calcium catalysed Beckmann rearrangements
A mild calcium catalysed Beckmann rearrangement has been realised, which forgoes the more traditional harsh reactions conditions associated with the transformation. The catalyst system is shown to be tolerant towards a wide variety of functional groups relevant to natural product synthesis and medicinal chemistry and the synthetic utility of the reaction has also been investigated. A preliminary mechanistic investigation was performed to understand the nature of the incoming nucleophile and a possible reaction pathway is described.
Kiely-Collins,Sechi,Brennan,McLaughlin
supporting information
p. 654 - 657
(2018/02/06)

Selective, Catalytic, and Metal-Free Coupling of Electron-Rich Phenols and Anilides Using Molecular Oxygen as Terminal Oxidant
Selective oxidative homo- and cross-coupling of electron-rich phenols and anilides was developed using nitrosonium tetrafluoroborate as a catalyst. Oxidative coupling of phenols revealed unusual selectivities, which translated into the unprecedented synthesis of inverse Pummerer-type ketones. Mechanistic studies suggest that oxidative coupling of phenols and anilides shares a common pathway via homolytical heteroatom-hydrogen bond cleavage. Nitrosonium salt catalysis was applied for cross-dehydrogenative coupling initiated by generation of heteroatom-centered radicals.
Bering, Luis,Vogt, Melina,Paulussen, Felix M.,Antonchick, Andrey P.
supporting information
p. 4077 - 4080
(2018/07/15)

CHEMICAL COMPOUNDS AS ANTIBIOTICS
The invention relates to a compound which is an indane derivative according to Formula (I), or a pharmaceutically acceptable salt thereof, [FORMULA (I)] wherein R1, R2, R3, n, R4, p? q, L, ?, X and m are as defined herein. The compounds are useful in the treatment of antibacterial infection either as stand alone antibiotics, or in combination with further antibiotics. The compounds can also be used in vitro, for example in cleaning compositions.
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Page/Page column 137

(2018/10/19)

Reagent- and Metal-Free Anodic C?C Cross-Coupling of Aniline Derivatives
The dehydrogenative cross-coupling of aniline derivatives to 2,2′-diaminobiaryls is reported. The oxidation is carried out electrochemically, which avoids the use of metals and reagents. A large variety of biphenyldiamines were thus prepared. The best results were obtained when glassy carbon was used as the anode material. The electrosynthetic reaction is easily performed in an undivided cell at slightly elevated temperature. In addition, common amine protecting groups based on carboxylic acids were employed that can be selectively removed under mild conditions after the cross-coupling, which provides quick and efficient access to important building blocks featuring free amine moieties.
Schulz, Lara,Enders, Mathias,Elsler, Bernd,Schollmeyer, Dieter,Dyballa, Katrin M.,Franke, Robert,Waldvogel, Siegfried R.
supporting information
p. 4877 - 4881
(2017/04/11)

Fused Amino Pyridines for the Treatment of Lung Cancer
The present invention relates to the use of compounds with fused amino pyridine core for the treatment of malignancies associated with brain and lung. The oral administration of compounds of the instant application results in effective brain penetration and provides for non-intrusive treatment of brain and lung tumors.
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Paragraph 0179

(2016/11/17)

Branch-selective alkene hydroarylation by cooperative destabilization: Iridium-catalyzed ortho-alkylation of acetanilides
An iridium(I) catalyst system, modified with the wide-bite-angle and electron-deficient bisphosphine dFppb (1,4-bis(di(pentafluorophenyl)phosphino)butane) promotes highly branch-selective hydroarylation reactions between diverse acetanilides and aryl- or alkyl-substituted alkenes. This provides direct and ortho-selective access to synthetically challenging anilines, and addresses long-standing issues associated with related Friedel-Crafts alkylations. An iridium(I) catalyst system modified with the wide-bite-angle and electron-deficient bisphosphine dFppb (1,4-bis(di(pentafluorophenyl)phosphino)butane) promotes highly branch-selective hydroarylation reactions between diverse acetanilides and aryl- or alkyl-substituted alkenes. This provides direct and ortho-selective access to synthetically challenging anilines.
Crisenza, Giacomo E. M.,Sokolova, Olga O.,Bower, John F.
supporting information
p. 14866 - 14870
(2016/02/09)

Structure-activity relationship in a purine-scaffold compound series with selectivity for the endoplasmic reticulum Hsp90 paralog Grp94
Grp94 is involved in the regulation of a restricted number of proteins and represents a potential target in a host of diseases, including cancer, septic shock, autoimmune diseases, chronic inflammatory conditions, diabetes, coronary thrombosis, and stroke. We have recently identified a novel allosteric pocket located in the Grp94 N-terminal binding site that can be used to design ligands with a 2-log selectivity over the other Hsp90 paralogs. Here we perform extensive SAR investigations in this ligand series and rationalize the affinity and paralog selectivity of choice derivatives by molecular modeling. We then use this to design 18c, a derivative with good potency for Grp94 (IC50 = 0.22 μM) and selectivity over other paralogs (>100- and 33-fold for Hsp90α/β and Trap-1, respectively). The paralog selectivity and target-mediated activity of 18c was confirmed in cells through several functional readouts. Compound 18c was also inert when tested against a large panel of kinases. We show that 18c has biological activity in several cellular models of inflammation and cancer and also present here for the first time the in vivo profile of a Grp94 inhibitor.
Patel, Hardik J.,Patel, Pallav D.,Ochiana, Stefan O.,Yan, Pengrong,Sun, Weilin,Patel, Maulik R.,Shah, Smit K.,Tramentozzi, Elisa,Brooks, James,Bolaender, Alexander,Shrestha, Liza,Stephani, Ralph,Finotti, Paola,Leifer, Cynthia,Li, Zihai,Gewirth, Daniel T.,Taldone, Tony,Chiosis, Gabriela
supporting information
p. 3922 - 3943
(2015/05/27)

Synthesis and biological evaluation of new rhodanine analogues bearing 2-chloroquinoline and benzo[h]quinoline scaffolds as anticancer agents
Several rhodanine derivatives (9-39) were synthesized for evaluation of their potential as anticancer agents. Villsmeier cyclization to synthesize aza-aromatic aldehydes, rhodanine derivatives preparation and Knoevenagel type of condensation between the rhodanines and aza-aromatic aldehydes are key steps used for the synthesis of 31 compounds. In vitro antiproliferative activity of the synthesized rhodanine derivatives (9-39) was studied on a panel of six human tumor cell lines viz. HGC, MNK-74, MCF-7, MDAMB-231, DU-145 and PC-3 cell lines. Some of the compounds were capable of inhibiting the proliferation of cancer cell lines at a micromolar concentration. Six compounds are found to be potent against HGC cell lines; compound 15 is found to be active against HGC - Gastric, MCF7 - Breast Cancer and DU145 - Prostate Cancer cell lines; compound 39 is potent against MNK-74; four compounds are found to be potent against MCF-7 cell lines; three compounds are active against MDAMB-231; nine compounds are found to be potent against DU-145; three compounds are active against PC-3 cell lines. These compounds constitute a promising starting point for the development of novel and more potent anticancer agents in future.
Ramesh, Vadla,Ananda Rao, Boddu,Sharma, Pankaj,Swarna,Thummuri, Dinesh,Srinivas, Kolupula,Naidu,Jayathirtha Rao, Vaidya
p. 569 - 580
(2014/07/21)

HSP90 INHIBITORS
The disclosure relates to Compounds of Formulae (IA) and (IB), and pharmaceutically acceptable salts thereof wherein Z1, Z2, Z3, Xa, Xb, Xc, Xd, Y, X2, and X4 are as defined herein, compositions comprising an effective amount of a Compound of Formula (IA) and/or (IB), and methods to treat or prevent a condition, such cancer which overexpresses Her-kinases, comprising administering to an patient in need thereof a therapeutically effective amount of a Compound of Formula (IA) or (IB). The disclosure further relates to compounds of Formulae (IA) and (IB) in which X2 is a leaving for introducing a radiolabeled atom, such as 124I or 131I and to methods of using such compounds in the preparation of radiolabeled compounds, particularly for use in imaging.
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Page/Page column 192

(2012/10/18)

Exploitation of a Candida antarctica lipase B-catalysed in situ carboxylic acid activation method for the synthesis of acetanilides
An efficient biocatalytic method has been developed which provides acetanilides in good yields which are otherwise inaccessible using Candida antarctica lipase B. The process exploits the enzyme-catalysed synthesis of an acyl donor and its in situ reaction with anilines. The method is potentially useful for the synthesis of bulky acetanilides since amide formation occurs through an active site-independent step.
Lal, Samridhi,Snape, Timothy J.
p. 80 - 86
(2012/10/30)

Synthesis of indoles via palladium-catalyzed C-H activation of N-aryl amides followed by coupling with alkynes
A convenient and efficient method for the construction of indole skeleton was developed via Pd-catalyzed C-H activation of N-aryl amides and subsequent coupling with alkynes. Both stoichiometric and catalytic versions have been successfully achieved.
Zhou, Feng,Han, Xiuling,Lu, Xiyan
supporting information; experimental part
p. 4681 - 4685
(2011/09/30)

The structure-activity relationships of A-ring-substituted aromathecin topoisomerase i inhibitors strongly support a camptothecin-like binding mode
Aromathecins are inhibitors of human topoisomerase I (Top1). These compounds are composites of several heteroaromatic systems, namely the camptothecins and indenoisoquinolines, and they possess notable Top1 inhibition and cytotoxicity when substituted at position 14. The SAR of these compounds overlaps with indenoisoquinolines, suggesting that they may intercalate into the Top1-DNA complex similarly. Nonetheless, the proposed binding mode for aromathecins is purely hypothetical, as an X-ray structure is unavailable. In the present communication, we have synthesized eight novel series of A-ring-substituted (positions 1-3) aromathecins, through a simple, modular route, as part of a comprehensive SAR study. Certain groups (such as 2,3-ethylenedioxy) moderately improve Top1 inhibition, and, often, antiproliferative activity, whereas other groups (2,3-dimethoxy and 3-substituents) attenuate bioactivity. Strikingly, these trends are very similar to those previously observed for the A-ring of camptothecins, and this considerable SAR overlap lends further support (in the absence of crystallographic data) to the hypothesis that aromathecins bind in the Top1 cleavage complex as interfacial inhibitors in a 'camptothecin-like' pose.
Cinelli, Maris A.,Morrell, Andrew E.,Dexheimer, Thomas S.,Agama, Keli,Agrawal, Surbhi,Pommier, Yves,Cushman, Mark
scheme or table
p. 5535 - 5552
(2010/10/01)

FUSED AMINO PYRIDINES FOR THE TREATMENT OF BRAIN TUMORS
The present invention relates to the use of compounds with fused amino pyridine core for the treatment of malignancies associated with brain and lung. The oral administration of compounds of the instant application results in effective brain penetration and provides for non-intrusive treatment of brain and lung tumors.
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(2010/08/07)

Tricyclic [1,2,4]triazine 1,4-dioxides as hypoxia selective cytotoxins
A series of novel tricyclic triazine-di-N-oxides (TTOs) related to tirapazamine have been designed and prepared. A wide range of structural arrangements with cycloalkyl, oxygen-, and nitrogen-containing saturated rings fused to the triazine core, coupled with various side chains linked to either hemisphere, resulted in TTO analogues that displayed hypoxia-selective cytotoxicity in vitro. Optimal rates of hypoxic metabolism and tissue diffusion coefficients were achieved with fused cycloalkyl rings in combination with both the 3-aminoalkyl or 3-alkyl substituents linked to weakly basic soluble amines. The selection was further refined using pharmacokinetic/pharmacodynamic model predictions of the in vivo hypoxic potency (AUCreq) and selectivity (HCD) with 12 TTO analogues predicted to be active in vivo, subject to the achievement of adequate plasma pharmacokinetics.
Hay, Michael P.,Hicks, Kevin O.,Pchalek, Karin,Lee, Ho H.,Blaser, Adrian,Pruijn, Frederik B.,Anderson, Robert F.,Shinde, Sujata S.,Wilson, William R.,Denny, William A.
supporting information; experimental part
p. 6853 - 6865
(2009/12/03)

FUSED AMINO PYRIDINE AS HSP90 INHIBITORS
The present invention relates to HSP90 inhibitors containing fused amino pyridine core that are useful as inhibitors of HSP90 and their use in the treatment of HSP90 related diseases and disorders such as cancer, an autoimmune disease, or a neurodegenerative disease.
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Page/Page column 59

(2008/12/08)

TRICYCLIC 1,2,4-TRIAZINE OXIDES AND COMPOSITIONS THEREFROM FOR THERAPEUTIC USE IN CANCER TREATMENTS
The invention relates to novel tricyclic 1,2,4-triazine-1-oxides and novel tricyclic 1,2,4-triazine-1,4-dioxides of formula: (I); and to related analogues, to their preparation, and to their use as hypoxia-selective drugs and radiosensitizers for cancer therapy, both alone or in combination with radiation and/or other anticancer drugs.
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Page/Page column 145

(2008/06/13)

Cyanuric chloride as a mild and active Beckmann rearrangement catalyst
The first general organocatalytic Beckmann rearrangement of ketoximes into amides has been realized by the catalytic use of cyanuric chloride. Furthermore, acids such as HCl and ZnCl2 are effective as cocatalysts with cyanuric chloride. For example, azacyclotridecan-2-one, which is synthetically useful as a starting material for nylon-12, was prepared in quantitative yield by the Beckmann rearrangement of cyclododecanone oxime (100 mmol scale) catalyzed by cyanuric chloride (0.5 mol %) and ZnCl2 (1 mol %). Copyright
Furuya, Yoshiro,Ishihara, Kazuaki,Yamamoto, Hisashi
p. 11240 - 11241
(2007/10/03)

Substituted quinazolines and analogs and use thereof
The invention relates to novel quinazolines and heterocycles which are antagonists or positive modulators of AMPA receptors, and the use thereof for treating, preventing or ameliorating neuronal loss associated with stroke, global and focal ischemia, CNS trauma, hypoglycemia and surgery, as well as treating or ameliorating neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease and Down's syndrome, treating, preventing or ameliorating the adverse consequences of the overstimulation of the excitatory amino acids, treating, preventing or ameliorating anxiety, psychosis, convulsions, chronic pain, glaucoma, retinitis, urinary incontinence, muscular spasm and inducing anesthesia, as well as for treating or ameliorating the adverse consequences of excitatory amino acid deficiency such as schizophrenia, myoclonus. Alzheimer's disease and malnutrition and neural maldevelopment, and as cognition and learning enhancers.
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(2008/06/13)

Bis(3,4-methylenedioxyphenylamino) derivatives and electrophotographic photoreceptor containing the derivatives
Disclosed are novel compounds useful in electrophotographic photoreceptors as charge-transporting materials having good miscibility with binder polymers and capable of forming a thin stable organic film having a high concentration; and an electrophotographic photoreceptor containing the same. The compounds are bis(3,4-methylenedioxyphenylamino) derivatives represented by general formula (1): wherein Ar1and Ar2each is an optionally substituted aryl group and Ar3is a phenylene group or an optionally substituted biphenylene group.
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(2008/06/13)

Water soluble camptothecin derivatives
The present invention relates to water soluble, camptothecin derivatives of formula (I). wherein A represents a moiety of the formula (IIA), (IIB) or (IIC): X is selected from the group consisting of alkyl, aryl, (CH2)mOR1, (CH2)mSR1 and (CH2)mNR1R2 wherein m is an integer of 0 to 6, and R1 and R2 are hydrogen, lower alkyl, aryl or together with the nitrogen form a 5-7 membered ring; q is an integer of 0 to 2; n represents the integer 1 or 2; p is an integer of 1 to 6; Y and W are selected from the group consisting of alkyl, aryl, alkoxy, aryloxy and amino, Q is oxygen or sulfur; P is phosphorus; J represents the atoms necessary to complete a 5 or 6 membered aromatic ring; and the pharmaceutically acceptable salts thereof; their use as topoisomerase inhibitors, their preparation; and their use in the treatment of cancer.
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(2008/06/13)

Imide derivatives for inhibiting the production of interleukin-1β and the production of tumor necrosis factor α
Imide compounds having a propioloyl group or pharmaceutically acceptable salts thereof which exhibit potent activities to inhibit the production of Interleukin 1-β and also the production of Tumor Necrosis Factor α. These imide compounds are useful as a prophylactic or therapeutic agent for inhibiting the production of Interleukin 1-β and the production of Tumor Necrosis Factor α, typically for such diseases as chronic rheumatism, sepsis, ulcerative colitis, Crohn's disease and many other related diseases in which Interleukin 1-β and/or Tumor Necrosis Factor α would participate.
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(2008/06/13)

Production of benzophenone derivatives
A method for producing a compound of the formula: wherein R is an acyl group or a silyl group, the rings A and B respectively may have one to four substituent(s), or a salt thereof, which comprists reacting a compound of the formula: wherein R has the same meaning as defined above, the ring A may have one to four substituents at the position(s) other than 2-position, or a salt thereof, with a compound of the formula: wherein Y is a hydroxyl group or a halogen atom, the ring B may have one to four substituent(s), or its salt, in the presence of a catalyst other than polyphosphonic acid. The method produces aminobenzophenone derivative of the formula (I) in a high purity, a high yield, with a conventional and commercially advantageous procedure.
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(2008/06/13)

Water soluble camptothecin derivatives
The present invention relates to water soluble, camptothecin derivatives of formula (I), STR1 wherein: 1) R1 and R2 represent independently, hydrogen, lower alkyl, C3-7)cycloalkyl, C3-7)cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl, lower alkoxy lower alkyl; ii) R1 represents hydrogen, lower alkyl, C3-7)cycloalkyl, C3-7)cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl or lower alkoxy lower alkyl, and R2 represents --COR3, wherein: R3 represents hydrogen, lower alkyl, perhalo-lower alkyl, C3-7)cycloalkyl, C3-7)cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl, lower alkoxy or lower alkoxy lower alkyl; or iii) R1 and R2 taken together with the linking nitrogen form a saturated 3 to 7 atom heterocyclic group of formula (IA) STR2 wherein: Y represents O, S, SO, SO2, CH2 or NR4 wherein: R4 represents hydrogen, lower alkyl, perhalo lower alkyl, aryl, aryl substituted with one or more lower alkyl, lower alkoxy, halogen, nitro, amino, lower alkyl amino, perhalo-lower alkyl, hydroxy lower alkyl, lower alkoxy lower alkyl groups or; --COR5, wherein: R5 represents hydrogen, lower alkyl, perhalo-lower alkyl, lower alkoxy, aryl, aryl substituted with one or more lower alkyl, perhalo-lower alkyl, hydroxy lower alkyl, lower alkoxy lower alkyl groups or; the pharmaceutically acceptable salts thereof; their use in the treatment of tumors and methods of their preparation.
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(2008/06/13)

Synthesis and Antitumor Activity of Novel Water Soluble Derivatives of Camptothecin as Specific Inhibitors of Topoisomerase I
The synthesis and antitumor activities of the novel water soluble camptothecin derivatives 7--10,11-(methylenedioxy)-(20S)-camptothecin trifluoroacetate (6) and 7--10,11-(ethylenedioxy)-(20S)-camptothecin trifluoroacetate (7) are described.The solubilities of compounds 6 and 7 were measured to be 4.5 and 5.8 mg/mL, respectively, in pH 5 acetate buffer in contrast to 0.003 mg/mL for camptothecin in the same buffer.In the purified topoisomerase I cleavable complex enzyme assay, compounds 6 and 7 demonstrated potent inhibition of topoisomerase I with IC50's of 300 and 416 nM, respectively, in comparison to 679 nM for camptothecin and 1028 nM for topotecan.In human tumor cell cytotoxicity assays, compounds 6 and 7 demonstrated potent antitumor activity against ovarian (SKOV3), ovarian with upregulated MDRp-glycoprotein (SKVLB), melanoma (LOX), breast (T47D), and colon (HT29) with IC50's ranging from 0.5 to 102 nM.Compounds 6 and 7 induced tumor regressions in the HT29 human colon tumor xenograft model and demonstrated similar rank order of potency compared to in vitro assay results.
Luzzio, Michael J.,Besterman, Jeffrey M.,Emerson, David L.,Evans, Michael G.,Lackey, Karen,et al.
p. 395 - 401
(2007/10/02)

Preparation of water soluble camptothecin derivatives
The present invention relates to the synthesis of water soluble, camptothecin derivatives of formula (I), STR1 wherein: n represents the integer 1 or 2; R1 represents independently, hydrogen, lower alkyl, (C3-7)cycloalkyl, (C3-7)cycloalkyl lower alkyl, lower alkenyl, hydroxy lower alkyl, lower alkoxy lower alkyl; and R2 represents hydrogen and the pharmaceutically acceptable salts thereof.
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(2008/06/13)

Imidazole derivatives
Tricyclic imidazole derivatives of the formula STR1 wherein R1 is 2-pyridyl optionally substituted by lower alkyl or lower alkoxy, n is the integer 0 or 1, R2 is hydrogen or lower alkyl, R3 and R4, independently, are hydrogen or lower alkyl, A is a group of the formula STR2 m is the integer 2 or 3, R5, R6, R7 and R8, independently, are hydrogen or lower alkyl, and R9 is hydrogen and R10 is hydrogen or lower alkyl or R9 and R10 taken together are oxo, provided that at least one of R3 and R4 is lower alkyl when A is a group of the formula and their pharmaceutically acceptable acid addition salts. The compounds of formula I inhibit gastric acid secretion and prevent the formation of gastric ulcers.
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(2008/06/13)

Topical inflammatory pharmaceutical formulations
A compound of the formula (I) may be prepared by known methods and may be used in the treatment of pain, inflammation or pyresis in mammals, by administration of the compound alone or in a pharmaceutical formulation suitable for administration to a mammal in need thereof. STR1
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(2008/06/13)