- Mechanisms of acid decomposition of dithiocarbamates. 5. Piperidyl dithiocarbamate and analogues
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(Chemical Equation Presented) In this work, the acid cleavage at 25°C in 20% v/v aqueous ethanol of a series of analogues of piperidine dithiocarbamate X(C2H4)2NCS2 - (X = CH2, CHCH3, NH, NCH3, S, O) was studied. The pH-rate profiles were obtained in the range of Ho -5 and pH 5. They all presented a dumbell shaped curve with a plateau from which the pH-independent first-order rate constant ko (or the specific acid catalysis kH) was calculated, in addition to the acid dissociation constant of the free (pKa) and conjugate acid (pK+) species of the DTC. LFERs of the kinetically determined pKa and pK+ versus pKN (pKa of parent amine) were used to characterize the reactive species and the structure of the transition state of the rate-determining step. For X = CH2, CH3CH the values of kH agree with those of alkDTCs in the strong base region of the Bronsted plot of log kH versus pKN where the transition state is close to a zwitterion formed by intramolecular water-catalyzed S-to-N proton transfer of the dithiocarbamic acid. However, when X = NH, CH3N, O, S, the reactive species is the DTC anion, which is as reactive as an arylDTC, and similarly, the pK+ values correspond to a parent amine that is about 3-4 pK units more basic. The solvent isotope effect indicated that the acid decomposition of these dithiocarbamate anions is specifically catalyzed by a Hydron anchimerically assisted by the heteroatom through a boat conformation.
- Humeres, Eduardo,Byung, Sun Lee,Debacher, Nito Angelo
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Read Online
- Selective reduction of N-nitroso aza-aliphatic cyclic compounds to the corresponding N-amino products using zinc dust in CO2–H2O medium
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[Figure not available: see fulltext.] A new method for reduction of N-nitroso aza-aliphatic cyclic compounds employing zinc in pressurized CO2–H2O medium has been developed. H2O and NH4Cl were used as hydrogen donors, and reduction was performed under environmentally benign conditions. The presented approach allowed to obtain the respective N-amino products selectively and in excellent yields (up to 97%).
- Yang, Weiqing,Lu, Xiang,Zhou, Tingting,Cao, Yongjing,Zhang, Yuanyuan,Ma, Menglin
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Read Online
- Study of the formation and thermal decomposition of an azo-bridged tricyclic ring system
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1-Amino-2-methyl-1,3-pentadienes were treated with dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate to give diazatricyclo[2.2.2.0]octenes and dimethyl 4-methylpyridazine-3,6-dicarboxylate, the product distribution being largely dependent on the nature of the amino substituent. Under similar conditions the analogous 1-morpholino-1,3-butadiene afforded dimethyl pyridazine-3,6-dicarboxylate as the major product. The tricyclic products underwent selective thermal decomposition to give dimethyl 4-methylpyridazine-3, 6-dicarboxylate in excellent yield. The proposed mechanism of the formation as well as of the decomposition was supported by quantum chemical calculations and experimental evidence. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.
- Novak, Zoltan,Vincze, Zoltan,Czegeny, Zsuzsanna,Magyarfalvi, Gabor,Smith, David M.,Kotschy, Andras
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Read Online
- Nickel-Catalyzed Amination of Aryl Chlorides with Amides
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A nickel-catalyzed amination of aryl chlorides with diverse amides via C-N bond cleavage has been realized under mild conditions. A broad substrate scope with excellent functional group tolerance at a low catalyst loading makes the protocol powerful for synthesizing various aromatic amines. The aryl chlorides could selectively couple to the amino fragments rather than the carbonyl moieties of amides. Our protocol complements the conventional amination of aryl chlorides and expands the usage of inactive amides.
- Li, Jinpeng,Huang, Changyu,Wen, Daheng,Zheng, Qingshu,Tu, Bo,Tu, Tao
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supporting information
p. 687 - 691
(2021/01/09)
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- Method for synthesizing 1-amino-4-methylpiperazine through catalytic hydrogenation
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The invention relates to a method for synthesizing 1-amino-4-methylpiperazine through catalytic hydrogenation. The invention discloses the green synthesis method for synthesizing 1-amino-4-methylpiperazine by hydrogenating 1-methyl-4-nitrosopiperazine in a water and organic mixed solvent system under the catalysis of an iron oxide and ferrous oxide supported palladium catalyst, wherein the methodcomprises the steps: adding 1-methyl-4-nitrosopiperazine into a paramagnetic Pd/Fe3O4-FeO catalyst, carrying out a hydrogenation reaction in a three-phase system of water, an organic solvent and the catalyst at a certain temperature, and finally, carrying out reduced pressure distillation separation to obtain the target product 1-amino-4-methylpiperazine. The 1-amino-4-methylpiperazine is preparedby innovatively using a catalytic hydrogenation method in a three-phase system, and compared with a traditional synthesis method, the method is more environmentally friendly and safer, and the cost is saved.
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Paragraph 0044-0046; 0068
(2020/07/28)
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- Biocatalytic Access to Piperazines from Diamines and Dicarbonyls
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Given the widespread importance of piperazines as building blocks for the production of pharmaceuticals, an efficient and selective synthesis is highly desirable. Here we show the direct synthesis of piperazines from 1,2-dicarbonyl and 1,2-diamine substrates using the R-selective imine reductase from Myxococcus stipitatus as biocatalyst. Various N- and C-substituted piperazines with high activity and excellent enantioselectivity were obtained under mild reaction conditions reaching up to 8.1 g per liter.
- Borlinghaus, Niels,Gergel, Sebastian,Nestl, Bettina M.
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p. 3727 - 3732
(2018/04/14)
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- N-methyl piperazine a process for the preparation of (by machine translation)
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The invention relates to a preparation method of N-methyl piperazine. The preparation method comprises the following steps: (1) carrying out reaction on iminodiacetonitrile (IDAN) and methanal under the acidic condition to prepare N-methyl iminodiacetonitrile; and (2) carrying out hydrogenation reaction on N-methyl iminodiacetonitrile at the temperature of 70-140 DEG C and the pressure of 2-8MPa, wherein a molecular-sieve modified zirconium-based superacid serves a carrier, and one or two or more of the active metals of Fe, Co, Ni, Ru and Rh serves/serve as a hydrogenation catalyst. Compared with the prior art, the preparation method provided by the invention has the advantages of high yield due to the adoption of the catalyst and low equipment investment. In addition, the raw materials for preparing the N-methyl piperazine are low in cost and are easy to obtain.
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Paragraph 0066-0074
(2019/02/02)
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- A catalytic hydrogenation preparing piperazine or alkyl piperazine method
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The invention discloses a method for preparing piperazidine or alkyl piperazidine by catalytic hydrogenation, which comprises the following steps: carrying out catalytic hydrogenation reaction on raw materials dihydroxy ethyl piperazidine or/and hydroxyethyl piperazidine under the action of a catalyst, and carrying out after-treatment to obtain the piperazidine or/and alkyl piperazidine, wherein the active component in the catalyst is one or more of Cu, Ni and Co. The dihydroxy ethyl piperazidine or hydroxyethyl piperazidine is used as the raw material to prepare the piperazidine or alkyl piperazidine by catalytic hydrogenation, thereby providing a brand-new synthesis technique of piperazidine or alkyl piperazidine. Meanwhile, the method can be utilized to implement the recovery of the waste liquor or byproduct containing dihydroxy ethyl piperazidine or hydroxyethyl piperazidine. Besides, the existing method can be utilized to separate the alkyl piperazidine in the product, thereby further enhancing the value of the product and lowering the preparation cost.
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Paragraph 0038-0039
(2017/04/26)
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- A method of manufacturing a mono-N-alkyl-piperazinecarboxylic
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The invention relates to a method for producing a mono-N-alkyl piperazine of formula (I), where R1 represents C1 to C5 alkyl or 2-(2-hydroxy-ethoxy) ethyl, by reacting diethanolamine (DEOA) of formula (II) with a primary amine of formula H2N-R1 (III) in the presence of hydrogen and a supported catalyst containing metal. The catalytically active mass of the catalyst, before reduction of the latter using hydrogen, contains oxygenic compounds of aluminum, copper, nickel and cobalt and between 0.2 and 5.0 wt. % oxygenic compounds of tin, calculated as SnO, and the reaction is carried out in the liquid phase at an absolute pressure ranging from 95 to 145 bar.
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Paragraph 0086-0089
(2018/11/22)
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- PROCESS FOR THE PREPARATION OF A MONO-N-ALKYLPIPERAZINE
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Process for the preparation of a mono-N-alkylpiperazine of the formula I in which R1 is C1- to C5-alkyl or 2-(2-hydroxyethoxy)ethyl, by reacting diethanolamine (DEOA) of the formula II with a primary amine of the formula H2N—R1 (III) in the presence of hydrogen and a catalyst molding, where the reaction is carried out in the liquid phase at an absolute pressure in the range from 150 to 250 bar and the amination is carried out by means of a catalyst molding, the precursor of which can be prepared according to a process in which (i) an oxidic material comprising copper oxide, aluminum oxide and lanthanum oxide is provided,(ii) pulverulent metallic copper and/or copper flakes and optionally graphite is added to the oxidic material,(iii) the mixture resulting from step ii is shaped to give a molding, where the oxidic material is obtainable by simultaneous or successive precipitation of the component copper oxide, of the component aluminum oxide and of the component lanthanum oxide and subsequent drying and calcination and, after the shaping according to step iii, the catalyst molding is calcined again.
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Paragraph 0093
(2014/01/07)
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- Process for the Preparation of a Mono-N-Alkypiperazine
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Process for the preparation of a mono-N-alkylpiperazine of the formula I in which R1 is C1- to C5-alkyl or 2-(2-hydroxyethoxy)ethyl, by reacting diethanolamine (DEOA) of the formula II with a primary amine of the formula H2N—R1 (III) in the presence of hydrogen and a supported, metal-containing catalyst, where the catalytically active mass of the catalyst, prior to its reduction with hydrogen, comprises oxygen-containing compounds of aluminum, copper, nickel and cobalt and, in the range from 0.2 to 5.0% by weight, oxygen-containing compounds of tin, calculated as SnO, and the reaction is carried out in the liquid phase at an absolute pressure in the range from 95 to 145 bar.
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Paragraph 0090-0093
(2014/01/07)
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- Novel antimalarial 3-azabicyclo[3.2.2]nonane derivatives
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The present invention relates to novel 3-azabicyclo[3.2.2]nonane derivatives of the general formula (I) or a pharmaceutically acceptable salt thereof wherein R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 are as defined in the specification. The novel 3-azabicyclo[3.2.2]nonane derivatives are particularly useful for treatment and prevention of malaria and trypanosomiasis.
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- 2,3,4,5-TETRAHYDRO-1H-1,5-BENZODIAZEPINE DERIVATIVE AND MEDICINAL COMPOSITION
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The present invention has its object to provide a 2,3,4,5-tetrahydro-1H-1,5-benzodiazepine derivative represented with the Formula (1) , or the pharmaceutically acceptable salt, which is effective as a therapeutic and prophylactic agent for diabetes, diabetic nephropathy, or glomerulosclerosis.
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- Deprotection of o-nitrobenzensulfonyl (nosyl) derivatives of amines mediated by a solid-supported thiol
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A new protocol based on a solid-supported thiol was developed for high yielding deprotection of o-nitrobenzensulfonyl amides derived from primary and secondary amines. The reaction can be carried out at room temperature for 24 hours or accelerated by microwave irradiation, going to completion in six minutes. Georg Thieme Verlag Stuttgart.
- Cardullo, Francesca,Donati, Daniele,Merlo, Giancarlo,Paio, Alfredo,Salaris, Margherita,Taddei, Maurizio
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p. 2996 - 2998
(2007/10/03)
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- N-methylation of nitrogen-containing heterocycles with dimethyl carbonate
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Reactivity of dimethyl carbonate, the environmentally friendly reagent, as methylating agent for nitrogen-containing heterocyclic compounds has been studied. Reactions of imidazole, pyrazole, pyrrole, morpholine, and piperazine with dimethyl carbonate to afford N-methylated products were reported. The reactions were carried out with neither catalyst nor solvent at a temperature range of 110-170°C under atmospheric pressure. Copyright Taylor & Francis, Inc.
- Ouk, Samedy,Thiebaud, Sophie,Borredon, Elisabeth,Chabaud, Bernard
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p. 3021 - 3026
(2007/10/03)
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- Selective reduction of alkenes, α,β-unsaturated carbonyl compounds, nitroarenes, nitroso compounds, N,N-hydrogenolysis of azo and hydrazo functions as well as simultaneous hydrodehalogenation and reduction of substituted aryl halides over PdMCM-41 catalyst under transfer hydrogen conditions
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Chemoselective reductions of alkenes, α,β-unsaturated carbonyl compounds, nitro and nitroso compounds, N,N-hydrogenolysis of azo and hydrazo functions as well as simultaneous reduction and hydrodehalogenation of substituted aryl halides, including bulkier substrates, were achieved by catalytic transfer hydrogenation (CTH) using mesoporous PdMCM-41 catalyst. The yields were practically unaffected upon recycling of the catalyst. Further, the CTH process is accomplished without affecting the reduction of any other reducible functional group.
- Selvam, Parasuraman,Sonavane, Sachin U.,Mohapatra, Susanta K.,Jayaram, Radha V.
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p. 3071 - 3075
(2007/10/03)
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- Monomethylation of nitrogeneous heterocycles
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A process for the monomethylation of nitrogenous heterocycles having at least one nitrogen atom bonded to a hydrogen atom by reacting the nitrogenous heterocycle with dimethyl carbonate at a temperature of between 100° and 200° C. and a pressure of between 0.93×105 Pa and 1.07×105 Pa while methanol produced during the reaction is distilled off as it is formed.
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- Method of treating a patient having precancerous lesions with phenyl quinazolinone derivatives
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Derivatives of 2-phenyl quinazolinones are useful for the treatment of patients having precancerous lesions. These compounds are also useful to inhibit growth of neoplastic cells.
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- SUBSTITUTED QUINAZOLINE DERIVATIVES AND THEIR USE AS INHIBITORS
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The use of a compound of formula (I) 1 or a salt, ester or amide thereof; where X is O, or S, S(O) or S(O)2, or NR6 where R6 is hydrogen or C1-6 alkyl,; R5 is an optionally substituted 5-membered heteroaromatic ring, R1, R2 ,R3, R4 are independently selected from various specified moieties, in the preparation of a medicament for use in the inhibition of aurora 2 kinase. Certain compounds are novel and these, together with pharmaceutical compositions containing them are also described and claimed
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- METHOD FOR TREATING CHRONIC PAIN USING MEK INHIBITORS
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The invention features a method for treating chronic pain using a compound selected from formulae (I), (II)A, (I)B and (I)C.
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- Benzothiazole derivatives with activity as adenosine receptor ligands
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The present invention relates to substituted benzothiazole derivitives and to their pharmaceutically acceptable salts useful for the treatment of diseases related to the adenosine receptor.
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- Tricyclic benzodiazepines as vasopressin receptor antagonists
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The invention is directed to tricyclic benzodiazepines useful as vasopressin receptor antagonists for treating conditions involving increased vascular resistance and cardiac insufficiency. Pharmaceutical compositions comprising tricyclic benzodiazepines of the present invention and methods of treating conditions such as hypertension, congestive heart failure, cardiac insufficiency, coronary vasospasm, cardiac ischemia, liver cirrhosis, renal vasospasm, renal failure, cerebral edema and ischemia, stroke, thrombosis, or water retention are also disclosed.
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- Benzenesulfonamide derivatives and their use as MEK inhibitors
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Benzenesulfonamides of formula (I), in which W is OR1, NR2OR1, NRARB, NR2NRARB, or NR2(CH2)2-4NRARBand the other variables as defined in the claims, are inhibitors of MEK and are effective in the treatment of proliferative diseases, cancer, stroke, heart failure, xenograft rejection, arthritis, cystic fibrosis, hepatomegaly, cardiomegaly, Alzheimer's disease, complications of diabetes, septic shock, and viral infection.
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- 2-aminopyridine derivatives and combinatorial libraries thereof
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The present invention relates to novel 2-aminopyridine derivative compounds of the following formula: wherein R1to R5have the meanings provided herein. The invention further relates to combinatorial libraries containing two or more such compounds, as well as methods of preparing 2-aminopyridine derivative compounds.
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- Pyrazolopyrimidinone CGMP PDE5 inhibitors for the treatment of sexual dysfunction
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There is provided compounds of formula IA and of formula IB, wherein R1, R2, R3, R4and A have meanings given in the description, which are useful in the curative and prophylactic treatment of medical conditions for which inhibition of a cyclic guanosine 3′,5′-monophosphate phosphodiesterase (e.g. cGMP PDE5) is desired.
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- Fused thiophene compounds and medicinal use thereof
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A condensed thiophene compound of the formula (I) wherein each symbol is as defined in the specification, a pharmaceutically acceptable salt thereof and hydrates thereof. The compound of the formula (I) of the present invention is useful as a novel antipsychotic agent which is effective for both positive symptoms and negative symptoms of schizophrenia, which is associated with less side effects such as extrapyramidal motor disorder and the like and which is less associated with serious side effects such as agranulocytosis and the like. In addition, this compound is also useful as a therapeutic agent of Alzheimer's disease and manic-depressive illness.
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- Ultrasound effect on the synthesis of 4-alkyl-(aryl)aminobenzaldehydes
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The sonochemical nucleophilic aromatic substitutions on 4-fluorobenzaldehyde with different azacycloalkanes and azoles have been studied. A beneficial ultrasound effect was observed, reactions were clean and high yields of the products were isolated after 15 min sonication.
- Magdolen, Peter,Me?iarová, Mária,Toma, ?tefan
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p. 4781 - 4785
(2007/10/03)
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- Hair revitalizing tonic composition containing a 2,2-dimethylpropanediol compound and use thereof
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Disclosed is a hair revitalizing tonic composition containing a dimethylpropanediol derivative of the formula: wherein R1and R2are each independently a C1-30hydrocarbon group which may be substituted, or a five- or six-membered heterocyclic group which contains1to4heteroatoms selected from oxygen, sulfur and nitrogen atoms and which may be substituted, R3is hydrogen atom, an alkyl group which may be substituted, an acyl group, an alkoxycarbonyl group, a phenoxycarbonyl group, or a carbamoyl group which may be substituted, and a and b are each 0 or 1, as well as a method for effecting hair growth promotion, hair growth stimulation, or hair loss prevention in mammals by using such a hair revitalizing tonic composition. Also disclosed is the use of a compound of formula (I) in the preparation of a hair revitalizing tonic composition. Thus, this invention can provide an excellent means of hair revitalization or hair loss prevention in mammals.
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- Method of treating a patient having precancerous lesions with phenyl cycloamino pyrimidinone derivatives
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Derivatives of Phenyl Cycloamino Pyrimidinone are useful for the treatment of patients having precancerous lesions. These compounds are also useful to inhibit growth of neoplastic cells.
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- Double prodrugs of potent GP IIb/IIIa antagonists
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The present invention relates to double prodrugs of pharmacologically active glycoprotein IIb/IIIa antagonists of the formula wherein R1 is selected from the group consisting of lower alkyl of about 2 to about 8 carbon atoms, cycloalkyl, and aralkyl; R is selected from the group consisting of alkoxy, wherein R50 is H or alkyl; and wherein R50 is H or alkyl; and pharmaceutically acceptable salts thereof.
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- Deprotection of sulfonamides using iodotrimethylsilane
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The deprotection of sulfonamides is achieved under neutral conditions by reaction with iodotrimethylsilane in acetonitrile at reflux.
- Sabitha, Gowravaram,Subba Reddy,Abraham, Sunny,Yadav
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p. 1569 - 1570
(2007/10/03)
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- Process for the manufacture of a tricyclic compound
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A process for preparing a compound of formula (I) or a phamaceutically-acceptable salt thereof, comprising: 1) reacting a compound. of formula (III), in which R is a straight or branched chain alkyl having from one to four carbon atoms, with an alkali metal hydroxide in an aqueous medium at a temperature of about 80° to 120° C. and time of about 20 to 100 hours to form a reaction product; 2) cyclizing the reaction product of step 1) with formic acid and formaldehyde to form a formiate compound; and 3) neutralizing the formiate compound of step 2) with an aqueous base.
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- Substituted pyrazoles as novel selective ligands for the human dopamine D4 receptor
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Two novel series of 3-(heterocyclylmethyl)pyrazoles have been synthesised and evaluated as ligands for the human dopamine D4 receptor. Compounds in series I (exemplified by 8k) have a phenyl ring joined to the 4-position of the pyrazole while those in series II (exemplified by 15j) have a 5-phenyl ring linked by a saturated chain to the 4-position of the pyrazole. Both series supplied compounds with excellent affinity for the human D4 and good selectivity over other dopamine receptors. Excellent selectivity over calcium, sodium, and potassium ion channels was also achieved. Copyright (C) 1997 Elsevier Science Ltd.
- Bourrain, Sylvie,Collins, Ian,Neduvelil, Joseph G.,Rowley, Michael,Leeson, Paul D.,Patel, Smita,Patel, Shil,Emms, Frances,Marwood, Rosemarie,Chapman, Kerry L.,Fletcher, Alan E.,Showell, Graham A.
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p. 1731 - 1743
(2007/10/03)
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- 14-substituted marcfortines and derivatives useful as antiparasitic agents
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There are disclosed 14α-hydroxymarcfortine derivatives of the natural products marcfortine A, B, C, and D useful in the treatment and prevention of helminth and arthropod infections of animals and plants. The synthetic derivatives are of Formula (I). STR1
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- Marcfortine/paraherquamide derivatives useful as antiparasitic agents
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There are disclosed 18-thiomarcfortine derivatives of the natural products marcfortine A, B and C, C-18 thioparaherquamide and derivatives thereof, novel N-1 marcfortines A, B, and C and derivatives thereof, novel N-1 paraherquamide and derivatives thereof usefull in the treatment and prevention of helninth and arthropod infections of animals and plants. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Examiner Robert T. Bond whose telephone number is (703)308-4711. The examiner can normally be reached on Monday through Friday from 8:00 AM to 4:30 PM.
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- Scavenger assisted combinatorial process for preparing libraries of amides, carbamates and sulfonamides
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This invention relates to a novel solution phase process for the preparation of amide, carbamate, and sulfonamide combinatorial libraries. These libraries have utility for drug discovery and are used to form wellplate components of novel assay kits.
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- Epoxyethane-/ethynesulfonamides with antifilarial activities degradation kinetics and inhibitory effect on filarial malate dehydrogenase and lactate dehydrogenase
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Some eppxyethane-/ethynesulfonamides had shown strong filaricidal activity with inconstant reproducibility as a result of a lack of stability in aqueous solution. The degradation in hydroxylic and aprotic solutions of two epoxyethanesulfonamides and one ethynesulfonamide was investigated using TLC, HPLC, GC and mass spectrometry. For both epoxydes, the degradation rate followed first-order kinetics and was more rapid in hydroxylic than in aprotic solutions. The degradation increased with the temperature whereas it was not modified with and without light exposure. Four kinds of degradation products were found: the first one involved the oxidation of the epoxyde bond, the second the breaking of the N-S bond, the third a desulfonation product and the fourth was not identified. In contrast, the stability of ethynesulfonamide was better than those of epoxyethanesulfonamide. These results suggest that epoxyethanesulfonamides should be kept at + 4 °C before being injected to animals during the study of biological activity. Since epoxyde compounds are known to have inhibitory effects on parasite energy metabolism enzymes, the compounds were evaluated on two major filarial enzymes: lactate dehydrogenase (LDH) and cytoplasmic malate dehydrogenase (MDH). Both epoxyethanesulfonamides showed only a slight inhibitory effect on filarial LDH and MDH confirming the evidence that the main mode of action of these compounds remains to discover. Moreover, ethynesulfonamide and the degradation products of both epoxyethanesulfonamides had no effect on LDH and MDH.
- Radembino, Nathalie,Loiseau, Philippe M.,Dessalles, Marie-Christine,Marchat, Laurence,Bories, Christian,Gayral, Philippe,Mahuzier, Georges
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p. 294 - 299
(2007/10/03)
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- Structure-activity relationship of newly synthesized quinoline derivatives for reversal of multidrug resistance in cancer
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The effect of 24 newly synthesized quinoline derivatives on tumor cell multidrug resistance (MDR) was examined in vitro. At low concentrations, these compounds enhanced the accumulation of [3H]vincristine in K562/ADM cells and reversed tumor cell MDR. The results of the structure-activity relationship analysis indicate that in highly active compounds the two aryl rings in the hydrophobic moiety deviate from a common plane, so they are capable of interacting with hydrogen bond donors of P-170 glycoprotein (P- gp) via π-hydrogen-π interactions. Other major structural features which influence the MDR-reversing activities of these compounds are a quinoline nitrogen atom and a basic nitrogen atom in piperazine. Furthermore, in highly active compounds, the distance between the hydrophobic moiety and the basic nitrogen atom (an atom connected to 2-hydroxypropoxyquinoline) must be at least 5 A?. Several compounds were found to reverse vincristine resistance in K562/ADM cells in vitro, and compound 16 (MS-209) was selected for clinical studies.
- Suzuki, Tsuneji,Fukazawa, Nobuyuki,San-nohe, Kunio,Sato, Wakao,Yano, Osamu,Tsuruo, Takashi
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p. 2047 - 2052
(2007/10/03)
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- PYRIDOPYRIMIDINONE ANTIANGINAL AGENTS
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Compounds of the formula and pharmaceutically acceptable salts thereof, wherein R 1 is H, C 1 -C 4 alkyl CN or CONR 4 R 5 ; R 2 is C 2 -C 4 alkyl; R 3 is SO 2 NR 6 R 7, NO 2, NH 2, NHCOR 8 NHSO 2 R 8 or N(SO 2 R 8) 2 ; R 4 and R 5 are each independently selected from H and C 1 -C 4 alkyl; R 6 and R 7 are each independently selected from H and C 1 -C 4 alkyl optionally substituted with CO 2 R 9, OH, pyridyl 5-isoxazolin-3-onyl, morpholino or 1-imidazolidin-2-onyl; or together with the nitrogen atom to which they are attached form a pyrrolidino, piperidino, morpholino, 1-pyrazolyl or 4-(NR 10)-1-piperazinyl group wherein any of said groups may optionally be substituted with one or two substituents selected from C 1 -C 4 alkyl, CO 2 R 9, NH 2 and OH; R 8 is C 1 -C 4 alkyl or pyridyl; R 9 is H or C 1 -C 4 alkyl; and R 10 is H, C 1 -C 4 alkyl or (hydroxy) C 2 -C 3 alkyl; are selected cGMP PDE inhibitors useful in the treatment of, inter alia, cardiovascular disorders such as angina, hypertension, heart failure and atherosclerosis
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- Antiatherosclerotic and antithrombotic 1-benzopyran-4-ones and 2-amino-1,3-benzoxazine-4-ones
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This invention relates to compounds of Formula I STR1 which are useful in association with a pharmaceutical carrier as antiatherosclerotic agents. In addition, various compounds of Formula I are useful inhibitors of cell proliferation.
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- QUINAZOLINONE ANTIANGINAL AGENTS
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Compounds of formula: and pharmaceutically acceptable salts thereofwhereinR1 is H, Q - Q alkyl, C j -Q alkoxy or CONRsRs;R2 is H or- CJ-C4 alkyl;R3 is C2-C4 alkyl;R4 is H, C2-C4 alkanoyl optionally substituted withNR7R8, (hydroxy)C2-C4 alkyl optionally substitutedwith NR7R8, CH=CHC02R9, CH=CHCONR7R8,CH2CH2C02R9, CH2CH2CONR7R8, S02NR7R8,S02NH(CH2)nNR7R8 or imidazolyl;R5 and Rs are each independently H or C1-C4 alkyl;R7 and R8 are each independently H or C1-C4 alkyl, ortogether with the nitrogen atom to which they areattached form a pyrrolidino, piperidino, morpholino or4-(NR10)-l-piperazinyl group wherein any of saidgroups is optionally substituted with CONR5R6;R9 is H or C1-C4 alkyl;R10 is H, C1-C3 alkyl or (hydroxy)C2-C3 alkyl; andn is 2, 3 or 4;with the proviso that R4 is not H when R1 is H, C1-C4 alkylor C1-C4 alkoxy; are selective cGMP PDE inhibitors usefiilin the treatment of cardiovascular disorders such as angina, hypertension, heart failure and atherosclerosis.
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- 8-vinyl- and 9-ethinyl-quinolone-carboxylic acids
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The invention relates to new 8-vinyl- and 8-ethinylquinolonecarboxylic acids, process for their preparation, and antibacterial agents and feed additives containing them.
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- Pyrazolopyrimidinone antianginal agents
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Compounds of the formula STR1 and pharmaceutically acceptable salts thereof are selective cGMP PDE inhibitors which are useful in the treatment of such diseases and adverse conditions as angina, hypertension, congestive heart failure, reduced blood vessel patency, peripheral vascular disease, stroke, bronchitis, chronic asthma, allergic asthma, allergic rhinitis, glaucoma, and diseases characterized by disorders of gut motility.
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- Benzazole derivatives, processes for their preparation containing such compounds and the use thereof
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The invention relates to new benzazole derivatives of the formula I STR1 wherein X is oxygen or sulphur, R1 is lower alkyl, lower alkenyl or cycloalkyl, R2 and R3 independently of one another are each hydrogen, lower alkyl or cycloalkyl radicals or taken together are a substituted or unsubstituted bivalent hydrocarbon residue of aliphatic character in which the carbon atoms of the chain may be interrupted by a heteroatom, R4 is either a group STR2 wherein R5 and R6 independently of one another are lower alkyl or cycloalkyl radicals, optionally substituted, or taken together R5 and R6 are a substituted or unsubstituted bivalent hydrocarbon residue of aliphatic character in which the carbon atoms of the chain may be interrupted by a heteroatom, or, R4 is a group STR3 where R7 is a lower alkyl group, and their salts and N-oxides. The products are useful as anthelmintic effective agents. The products can be prepared to methods known per se.
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- Antiatherosclerotic and antithrombotic 2-amino-6-phenyl-4H-pyran-4-ones
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This invention relates to compounds of Formula I STR1 which are useful as antiatherosclerotic agents and inhibitors of cell proliferation for the treatment of proliferative diseases. In addition, various compounds of Formula I are useful inhibitors of platelet aggregation.
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- N-SUBSTITUTED DERIVATIVES OF (ALPHA)-MERCAPTO ALKYLAMINES, THEIR PREPARATION PROCESS AND THE INTERMEDIATES OBTAINED, THEIR USE AS MEDICAMENTS AND THE COMPOSITIONS CONTAINING THEM
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Novel α-mercapto-alkylamines in all possible racemic, enantiomeric and diastereoisomeric forms of the formula STR1 wherein n, R 1, R 2, X, A, R 3A and R 4A are set forth in the claims and their non-toxic, pharmaceutically acceptable acid addition salts having excellent analgesic, psychotropic and enkephalinase inhibiting properties.
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- Complexation and Photoinduced Electron-transfer Reaction between Perfluoroalkyl Iodides and N,N,N',N'-Tetramethylphenylene-1,4-diamine, Anilines and Piperazines
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Treatment of tetrafluoro-1,2-diiodoethane 1a or dodecafluoro-1,6-diiodohexane 1b with N,N,N',N'-tetramethylphenylene-1,4-diamine 2 gave 1 + 1 solid complexes 3a or 3b in high yields.Complex 3a decomposed to give tetrafluoroethylene, iodine and 2 when irradiated with UV or heated.Complex 3b was converted into 6H-dodecafluorohexyl-N,N,N',N'-tetramethylphenylene-1,4-diamine 4 when irradiated with UV.On treatment of 1a and 1b with piperazine 6a and N,N'-dimethylpiperazine 6b, 1 + 1 solid complexes 7 were similarly obtained.However, heating or irradiating 7 gave no perfluoroalkylated products.Irradiating a mixture of 2 or anilines 13 and perfluoroalkyl iodides 10 in dimethylformamide also gave perfluoroalkylated products.The photoinduced electron transfer reaction involved radical cation 2*+ as a reactive intermediate which was detected by EPR techniques.
- Chen, Qing-Yun,Li, Zhan-Ting,Zhou, Cheng-Min
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p. 2457 - 2462
(2007/10/02)
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- New peptide compounds having a lactone or cycloamide structure
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New peptide compounds having a lactone or cycloamide structure and containing a saturated bicyclic structure, pharmaceutically-acceptable acid addition salts thereof, method for the preparation thereof, pharmaceutical compositions containing the same, and use thereof for the stimulation of cyclic AMP in the cerebral tissue and consequently increasing the metabolic capacities of the brain, thereby making them of interest in the treatment of diseases of the central nervous system or disorders approximating normal or pathological aging, are disclosed.
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- Pharmaceutical compositions of N-heterocyclic benzenesulfonamides and their use
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The invention relates to new N-cyclic benzenesulfonamides, their process of preparation and their use as active substance of pharmaceutical compositions. The new benzenesulfonamides according to the invention correspond to the following general formula (I): STR1 in which: V represents, for example, hydrogen, W represents, for example CF3, X represents, for example, hydrogen, Y represents, for example, hydrogen, n is 2 or 3, Z represents, for example, the group NR4, in which R4 represents, for example, hydrogen. These compounds are useful in pharmaceutical compositions for the treatment of nervous disorders with anxiety.
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