- Synthesis of α-substituted 2-(1H-1,2,4-triazol-3-yl)acetates and 5-amino-2,4-dihydro-3H-pyrazol-3-ones via the Pinner strategy
-
A series of 2-(1H-1,2,4-triazol-3-yl)acetates, as well as 4-mono- and 4,4-disubstituted 5-amino-2,4-dihydro-3H-pyrazol-3-ones (including spirocyclic derivatives) have been synthesized using the Pinner reaction strategy. α-Mono- and α,α-disubstituted ethyl cyanoacetates were converted into the corresponding carboxyimidate salts that served as the key intermediates. Their further reaction with formylhydrazide or hydrazine hydrate provided triazolylacetates or aminopyrazolones (including spirocyclic derivatives), depending on the structure of the starting Pinner salt and the nature of the nucleophile. The scope and limitations of the developed synthetic method have been established.
- Khomenko, Dmytro M.,Doroshchuk, Roman O.,Ivanova, Hanna V.,Zakharchenko, Borys V.,Raspertova, Ilona V.,Vaschenko, Oleksandr V.,Shova, Sergiu,Dobrydnev, Alexey V.,Moroz, Yurii S.,Grygorenko, Oleksandr O.,Lampeka, Rostyslav D.
-
supporting information
(2021/03/17)
-
- Preparation method of di-tert-butyl-2-(2-ethoxy-2-oxymethyleneethyl)dihydro-3H-imidazopyridine dicarboxylate
-
The invention relates to a preparation method of di-tert-butyl-2-(2-ethoxy-2-oxymethyleneethyl)dihydro-3H-imidazopyridine dicarboxylate, and mainly solves the technical problem that no suitable industrial synthesis method is available at present. The method comprises the following three steps: 1, adding ethanol into methyl tert-butyl ether into which saturated hydrochloric acid gas is introduced,and reacting a compound 1 with ethanol to obtain a compound 2; 2, reacting the compound 2 with 3,4-diaminopyridine in ethyl alcohol, concentrating, and reacting the obtained crude product in glacial acetic acid to obtain a compound 3, and 3, reacting the compound 3 with palladium carbon and Boc anhydride in ethyl alcohol to obtain a final compound 4, wherein the reaction formula is shown in the specification.
- -
-
Paragraph 0007; 0008
(2020/09/12)
-
- 1,5,7-TRISUBSTITUTED ISOQUINOLINE DERIVATIVES, PREPARATION THEREOF, AND USE THEREOF IN MEDICINES
-
The present disclosure relates to 1,5,7-trisubstituted isoquinoline derivatives, their preparation and pharmaceutical use. In particular, the present disclosure discloses a compound of formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate or prodrug thereof, and a preparation method and use thereof. The definitions of the groups in the formula can be found in the specification and claims.
- -
-
Paragraph 0150; 0428-0429
(2020/08/30)
-
- Pyridine triazole modified coumarin Cu2 + The preparation method of the fluorescent probe (by machine translation)
-
Pyridine triazole modified coumarin Cu2 + fluorescent probe preparation method, the invention relates to a triazole modified coumarin Cu pyridine2 + Fluorescent probe is 3 - formyl - 7 - (diethylamino) coumarin Schiff base, the preparation method comprises preparing a compound (A), compound (B) and compound (C) 3 - formyl - 7 - (diethylamino) coumarin Schiff base three steps. 3 - Formyl - 7 - (diethylamino) coumarin Schiff base as a fluorescent probe in the detection of copper, has good light stability, high fluorescence quantum yield, storck large displacement and the like, can be fast, efficient, single-minded identification in an aqueous solution of copper ion, which is a fast high sensitivity fluorescence probe, other common metal ion has a stronger anti-interference capability, real-time monitoring and detecting the stability is high, can be used for qualitative, quantitative detection environment in the copper ion, to the cupric ion detection has very good application value. The reaction of the invention easy control of the condition, the operation is convenient, and the yield is high. (by machine translation)
- -
-
Paragraph 0013; 0036; 0041-0042; 0049; 0053-0054
(2019/04/17)
-
- Energetic compounds featuring bi(1,3,4-oxadiazole): a new family of insensitive energetic materials
-
In this contribution, 5,5′-bis(trinitromethyl)-2,2′-bi(1,3,4-oxadiazole) (4) and 11 nitrogen-rich salts featuring bi(1,3,4-oxadiazole) were synthesised. Compound 4 was obtained by nitration of 2,2′-bi(1,3,4-oxadiazolyl)-5,5′-diacetic acid and the salts (6, 8-17) were prepared by facile deprotonation and metathesis reactions. All compounds were characterized by IR, multinuclear NMR spectroscopy and elemental analysis. The structures of 6, 9 and 15 were further confirmed by single crystal X-ray diffraction. The physicochemical as well as energetic properties of these compounds including density, thermal stability and sensitivity were investigated. Except for 12 and 15, most of the salts decompose at temperatures over 180 °C. The performance data from the calculated heats of formation and experimental densities indicate that many of the salts have potential applications as energetic materials. The tested sensitivities of these compounds illustrate that they are less sensitive than RDX towards impact, friction and electrostatic discharge.
- Tian, Jiawei,Xiong, Hualin,Lin, Qiuhan,Cheng, Guangbin,Yang, Hongwei
-
p. 1918 - 1924
(2017/03/09)
-
- REMOVAL OF SENESCENCE-ASSOCIATED MACROPHAGES
-
In various aspects and embodiments provided are compounds, compositions and methods relating to aging, senescent cells (SCs) and/or senescence associate macrophages (SAMs). In certain aspects and embodiments provided are compounds and compositions that selectively kill or reprogram senescent cells (SCs) and or senescence associate macrophages (SAMs) and associated methods. In some embodiments, the compounds compositions and methods treat or reverse aging and/or age-related diseases.
- -
-
Paragraph 0341; 0342
(2017/12/15)
-
- Tetranuclear Zn(II) and mononuclear Ni(II) based coordination polymers derived from a pair of isomeric 1,2,4-triazole ligands 3,5-disubstituted by pyridine and acetate ethyl ester groups
-
A pair of isomeric compounds, namely L1-Et [2-(5-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl)acetate ethyl ester] and L3-Et [2-(5-(pyridin-3-yl)-4H-1,2,4-triazol-3-yl)acetate ethyl ester], has been synthesized in this work, and they are used as multi-dentate ligands to react with certain transition-metal ions under solvothermal conditions. As a result, two three-dimensional (3D) coordination polymers, i.e. {[Zn(L1)(H2O)]ClO4·2H2O·0.5MeOH}n (C1) and {[Ni(L2)2](ClO4)2·2H2O}n (C3), have been yielded and structurally characterized, where ligand L2 is found to be the decomposition product of ligand L3-Et. It is noted that a novel tetranuclear Zn4(L1)4 based cluster-organic framework is constructed in the case of C1 exhibiting a three-dimensional (3D) 2-fold interpenetrating diamond structure. By comparing the structures of C1 and C3, it is concluded that the competition between metal-ion complexation and ligand decomposition leads to the formation of different coordination polymers.
- Hu, Bin,Wang, Yue-Hua,Qian, Hui-Fen,Peng, Yu-Xin,Huang, Wei
-
p. 138 - 143
(2016/02/03)
-
- A New Synthesis of 2-Aminoindoles and 6-Aminopyrrolo[3,2- d ]pyrimidines from π-Deficient 1,2-Dihaloarenes and Geminal Enediamines
-
An efficient approach for the synthesis of fused 2-aminopyrroles via geminal enediamines and π-deficient 1,2-dihaloarenes is presented. The two-step methodology includes aromatic nucleophilic substitution of the activated halogen of dihaloarene with enediamine C-nucleophilic center followed by Cu-catalyzed intramolecular N-arylation. This approach allows access to a variety of 2-amino-6-nitroindoles and 6-aminopyrrolo[3,2-d]pyrimidines (including N-mono- and N,N-disubstituted) in moderate and good yields under mild conditions.
- Mishina, Maria S.,Ivanov, Alexander Yu.,Lobanov, Pavel S.,Dar'In, Dmitrii V.
-
supporting information
p. 2851 - 2862
(2016/08/30)
-
- BIARYL COMPOUNDS USEFUL FOR THE TREATMENT OF HUMAN DISEASES IN ONCOLOGY, NEUROLOGY AND IMMUNOLOGY
-
The present invention provides compounds and compositions thereof which are useful as inhibitors of Bruton's tyrosine kinase and which exhibit desirable characteristics for the same.
- -
-
-
- Oxidation strategy for the synthesis of regioisomeric spiroisobenzofuranopyrroles: Facile entries to spiro[isobenzofuran-1,2′-pyrrole] and Spiro[isobenzofuran-1,3′-pyrrole] derivatives
-
Two practical and efficient approaches have been developed to synthesize two kinds of racemic spiroisobenzofuranopyrrole analogues as regioisomers. In the presence of sodium periodate, cis-indeno[1,2-b]pyrrol-4(1H)-ones were converted into spiro[isobenzofuran-1,2′-pyrrole] derivatives by a two-step process. In addition, oxidative reactions promoted by lead tetraacetate were demonstrated using cis-indeno[2,1-b]pyrrol-8(1H)-ones as substrates, affording spiro[isobenzofuran-1,3′-pyrrole] derivatives. The remarkable features of two approaches included mild and convenient reaction conditions, a broad substrate scope, and moderate to excellent yields. Possible mechanisms were proposed based on the comparison of the intermediates and products.
- Fan, Yefeng,Liu, Song,Chen, Nanyang,Shao, Xusheng,Xu, Xiaoyong,Li, Zhong
-
supporting information
p. 393 - 403
(2015/02/19)
-
- Discovery of hepatitis C Virus NS3-4A protease inhibitors with improved barrier to resistance and favorable liver distribution
-
Given the emergence of resistance observed for the current clinical-stage hepatitis C virus (HCV) NS3 protease inhibitors, there is a need for new inhibitors with a higher barrier to resistance. We recently reported our rational approach to the discovery of macrocyclic acylsulfonamides as HCV protease inhibitors addressing potency against clinically relevant resistant variants. Using X-ray crystallography of HCV protease variant/inhibitor complexes, we shed light on the complex structural mechanisms by which the D168V and R155K residue mutations confer resistance to NS3 protease inhibitors. Here, we disclose SAR investigation and ADME/PK optimization leading to the identification of inhibitors with significantly improved potency against the key resistant variants and with increased liver partitioning.
- Moreau, Benoi?t,O'Meara, Jeff A.,Bordeleau, Josée,Garneau, Michel,Godbout, Cedrickx,Gorys, Vida,Leblanc, Mélissa,Villemure, Elisia,White, Peter W.,Llinàs-Brunet, Montse
-
p. 1770 - 1776
(2014/04/03)
-
- PYRIMIDINEDIONE COMPOUNDS AGAINST CARDIAC CONDITIONS
-
Provided are novel pyrimidine dione compounds and pharmaceutically acceptable salts thereof, that are useful for the treatment of hypertrophic cardiomyopathy (HCM) and conditions associated with left ventricular hypertrophy or diastolic dysfunction. The synthesis and characterization of the compounds and pharmaceutically acceptable salts thereof, are described, as well as methods for treating HCM and other forms of heart disease.
- -
-
Paragraph 0149-0150
(2015/01/07)
-
- Synthesis and cholinesterase inhibition activity of new pyrrolopyrimidine derivatives
-
Cholinesterase plays a vital role in the decline of cholinergic transmission and thus can contribute to the development of Alzheimer's disease (AD). Thus, compounds that can inhibit acetylcholinesterase (AChe) and butyrylcholinesterase (BuChe) are the potential drugs for the treatment of AD. A series of novel pyrrolopyrimidine derivatives was synthesized and evaluated for their inhibitory activity against cholinesterase by Ellman method. Among the ten newly synthesized compounds, 4-(4-((4-(difluoromethoxy)phenyl)amino)-7H-pyrrolo [2,3-d]pyrimidin-6-yl)benzoate was the most potent molecule identified with the IC50 values of 18 μM and 17 uM on AChe and BuChe respectively.
- Roopashree, Rangaswamy,Swaroop, Toreshettahally Ramesh,Jagadish, Swamy,Mohan, Chakrabhavi Dhananjaya,Rangappa, Kanchugarakoppal Subbegowda
-
p. 1143 - 1148
(2015/03/31)
-
- HETEROCYCLIC COMPOUNDS AND USES THEREOF
-
Compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein.
- -
-
Paragraph 00664
(2013/03/26)
-
- Development of macrocyclic inhibitors of HCV NS3/4A protease with cyclic constrained P2-P4 linkers
-
A series of macrocyclic compounds containing a cyclic constraint in the P2-P4 linker region have been discovered and shown to exhibit excellent HCV NS3/4a genotype 3a and genotype 1b R155 K, A156T, A156 V, and D168 V mutant activity while maintaining high rat liver exposure. The effect of the constraint is most dramatic against gt 1b A156 mutants where ~20-fold improvements in potency are achieved by introduction of a variety of ring systems into the P2-P4 linker.
- Rudd, Michael T.,McIntyre, Charles J.,Romano, Joseph J.,Butcher, John W.,Holloway, M. Katharine,Bush, Kimberly,Nguyen, Kevin T.,Gilbert, Kevin F.,Lyle, Terry A.,Liverton, Nigel J.,Wan, Bang-Lin,Summa, Vincenzo,Harper, Steven,Rowley, Michael,Vacca, Joseph P.,Carroll, Steven S.,Burlein, Christine,Dimuzio, Jillian M.,Gates, Adam,Graham, Donald J.,Huang, Qian,Ludmerer, Steven W.,McClain, Stephanie,McHale, Carolyn,Stahlhut, Mark,Fandozzi, Christine,Taylor, Anne,Trainor, Nicole,Olsen, David B.,McCauley, John A.
-
supporting information
p. 7207 - 7213
(2013/01/15)
-
- A SAR study of novel antiproliferative ruthenium and osmium complexes with quinoxalinone ligands in human cancer cell lines
-
A series of ruthenium(II) arene complexes with 3-(1H-benzimidazol-2-yl)-1H- quinoxalin-2-one, bearing pharmacophoric groups of known protein kinase inhibitors, and related benzoxazole and benzothiazole derivatives have been synthesized. In addition, the corresponding osmium complexes of the unsubstituted ligands have also been prepared. The compounds have been characterized by NMR, UV-vis, and IR spectroscopy, ESI mass spectrometry, elemental analysis, and by X-ray crystallography. Antiproliferative activity in three human cancer cell lines (A549, CH1, SW480) was determined by MTT assays, yielding IC50 values of 6-60 μM for three unsubstituted metal-free ligands, whereas values for the metal complexes vary in a broad range from 0.3 to 140 μM. Complexation with osmium of quinoxalinone derivatives with benzimidazole or benzothiazole results in a more consistent increase in cytotoxicity than complexation with ruthenium. For selected compounds, the capacity to induce apoptosis was confirmed by fluorescence microscopy and flow-cytometric analysis, whereas cell cycle effects are only moderate.
- Ginzinger, Werner,Mühlgassner, Gerhard,Arion, Vladimir B.,Jakupec, Michael A.,Roller, Alexander,Galanski, Markus,Reithofer, Michael,Berger, Walter,Keppler, Bernhard K.
-
supporting information; experimental part
p. 3398 - 3413
(2012/06/04)
-
- Macrocyclic Compounds As Antiviral Agents
-
A class of macrocyclic compounds of formula (I), wherein R1, R3, R4, Ra, Rb, A, Z, Y, X, M, W, n and m are defined herein, that are useful as inhibitors of viral proteases, particularly the hepatitis C virus (HCV) NS3 protease, are provided. Also provided are processes 5 for the synthesis and use of such macrocyclic compounds for treating or preventing HCV infection. Formula (I):
- -
-
-
- An efficient large-scale synthesis of alkyl 5-hydroxy-pyridin- and pyrimidin-2-yl acetate
-
The synthesis of methyl 2-(5-hydroxy-3-methoxypyridin-2-yl)acetate and alkyl 2-(5-hydroxypyrimidin-2-yl)acetate is described. Methodology for an efficient access to 5-hydroxy-pyridin- and pyrimidin-2-yl acetate cores has been developed. Based on the difference in halogen reactivity, 5-bromo-2-chloropyridine and its pyrimidine analogue were functionalized judiciously by SNAr and palladium-catalyzed reactions. The outlined strategy provides a high-yielding route suitable for large-scale synthesis of these compounds as well as paves the way for a potential rapid access to other heterocyclic analogues.
- Morgentin, Rémy,Jung, Frédéric,Lamorlette, Maryannick,Maudet, Micka?l,Ménard, Morgan,Plé, Patrick,Pasquet, Georges,Renaud, Fabrice
-
experimental part
p. 757 - 764
(2009/04/07)
-
- Synthesis of new 2-substituted pyrido[2,3-d]pyrimidin-4(1H)-ones and their antibacterial activity
-
2-Substituted-5,7-dimethyl pyrido[2,3-d]pyrimidin-4(1H)-ones (8) were synthesized by oxidation of 2-substituted-5,7-dimethyl dihydropyrido[2,3-d]pyrimidin-4(1H)-ones (7) which were in turn prepared from 2-amino-4,6-dimethyl nicotinamide (5) and substituted aryl aldehydes (6). 2-Amino-4,6-dimethyl nicotinamide (5) was prepared from ethyl cyanoacetate (1) via malonamamidine hydrochloride (3). The compounds were characterized by IR, NMR, MS and elemental analyses. Compounds 7 and 8 were screened for antibacterial activity against Gram positive and Gram negative bacteria. Dehydrogenated compounds (8) showed less antibacterial activity than the compounds 7. Among all the test compounds screened for antibacterial activity 7c (1.25 μg/ml) showed greater activity. All the synthesized compounds were found inactive when screened for antifungal activity at the concentration of 200 μg/ml.
- Lakshmi Narayana,Raghu Ram Rao,Shanthan Rao
-
experimental part
p. 1369 - 1376
(2009/09/27)
-
- TRIAZOLOPYRIDINE DERIVATIVES AS HERBICIDES
-
Compounds of formula (I), wherein the substituents are as defined in claim 1, are suitable for use as herbicides.
- -
-
Page/Page column 34, 53
(2008/06/13)
-
- FUSED BICYCLIC PYRIMIDINES AS PTK INHIBITORS CONTAINING A ZINC BINDING MOIETY
-
The present invention relates to fused bicyclic pyrimidine containing zinc- binding moiety based derivatives that have unique properties as protein tyrosine kinase (PTK) inhibitors and their use in the treatment of PTK related diseases and disorders such as cancer. The said derivatives may further act as HDAC inhibitors.
- -
-
Page/Page column 70
(2008/06/13)
-
- HCV NS3 PROTEASE INHIBITORS
-
The present invention relates to macrocyclic compounds of formula (I) that are useful as inhibitors of the hepatitis C virus (HCV) NS3 protease, their synthesis, and their use for treating or preventing HCV infections. (I)
- -
-
Page/Page column 44
(2008/12/05)
-
- HCV NS3 PROTEASE INHIBITORS
-
The present invention relates to macrocyclic compounds of formula (I) that are useful as inhibitors of the hepatitis C virus (HCV) NS3 protease, their synthesis, and their use for treating or preventing HCV infections.
- -
-
Page/Page column 48
(2008/12/05)
-
- MULTI-FUNCTIONAL SMALL MOLECULES AS ANTI-PROLIFERATIVE AGENTS
-
The present invention relates to the compositions, methods, and applications of a novel approach to selective inhibition of several cellular or molecular targets with a single small molecule. More specifically, the present invention relates to multi-functional small molecules wherein one functionality is capable of inhibiting histone deacetylases (HDAC) and the other functionality is capable of inhibiting a different cellular or molecular pathway involved in aberrant cell proliferation, differentiation or survival.
- -
-
Page/Page column 254-255
(2008/06/13)
-
- HEPATITIS C INHIBITOR PEPTIDE ANALOGS
-
The compounds of formula I wherein R1, R2, R3 , R4 and R5 are defined herein, are useful as inhibitors of the hepatitis C virus NS3 protease The invention further relates to azalactone compounds of the formula (II) which can be reacted with an amide anion to produce the HCV NS3 protease inhibitors of formula (I)
- -
-
Page/Page column 36
(2010/11/25)
-
- HEPATITIS C INHIBITOR DIPEPTIDE ANALOGS
-
The present invention relates to compounds of formula (I): wherein R1, R2, R4, n and m are as defined herein and R3 is selected from: (i) -C(O)OR31 wherein R31 is (C1-6)alkyl or aryl, wherein the (C1-6)alkyl is optionally substituted with one to three halogen substituents; (ii) -C(O)NR32R33, wherein R32 and R33 are each independently selected form H, (C1-6)alkyl, and Het; (iii) -SOvR34, wherein v is 1 or 2 and R34 is selected from: (C1-6)alkyl, aryl, Het, and NR32R33 wherein R32 and R33 are as defined above; and (iv) -CO(O)-R35, wherein R35 is selected from (C1-8)alkyl, (C3-7)cycloalkyl-(C1-4)alkyl, aryl, aryl-(C1-6)alkyl, Het and Het-(C1-6)alkyl, each of which are optionally substituted with one or more substituents each independently selected from halo, (C1-6)alkyl, (C3-7)cycloalkyl, aryl, Het, hydroxyl, -O-(C1-6)alkyl, -S-(C1-6)alkyl, -SO-(C1-6)alkyl, -SO2-(C1-6)alkyl, -O-aryl, -S-aryl, -SO-aryl and -SO2-aryl, wherein the aryl portion of the -O-aryl, -S-aryl, -SO-aryl and -SO2-aryl are each optionally substituted with one to five halo substituents. The present invention further relates to pharmaceutical compositions containing the compounds of formula (I) and methods for using these analogs in the treatment of HCV infection.
- -
-
Page/Page column 66-67
(2008/06/13)
-
- Hepatitis C inhibitor peptide analogs
-
Compounds of formula (I): wherein R1, R2, R3, R4, R5, Y, n and m are as defined herein. The compounds are useful as inhibitors of HCV NS3 protease.
- -
-
Page/Page column 27
(2010/02/15)
-
- HEPATITIS C INHIBITOR PEPTIDE ANALOGS
-
The invention relates to compounds of formula (I) wherein R', R2, R3, R4, R5, R6, Y, n and m are as defined herein. The compounds are useful for the treatment and prevention of hepatitis C viral infections in mammals by inhibiting HCV NS3 protease. The invention further relates to azalactone compounds of the formula (III) which can be reacted with an amide anion to produce the compounds of formula (I).
- -
-
Page/Page column 80-81
(2010/02/15)
-
- Synthesis and photochromic properties of 2-(3-nitro-2-pyridylmethyl)benzazoles
-
2-(3-Nitro-2-pyridylmethyl)benzazoles were synthesized, and their photochromic properties were studied by flash photolysis. Introduction of a nitropyridyl instead of the nitrophenyl moiety into the 2-methyl group insignificantly increases the basicity of the methylene group. Nitropyridyl-substituted benzazoles give rise to three detectable photoinduced forms: the corresponding union at pH > 10, azamerocyanine at pH ≈ 4, and monomethinecyanine at pH ≈ 1. Irradiation of solutions of weakly basic henzoxazole and benzothiazole derivatives at pH ≈ 4 results in formation of neutral chelate structures in which the hydrogen atom is linked simultaneously to two nitrogen atoms: one in the pyridine ring, and the second, in the azole ring.
- Zakhs,Ponyaev,Subbotina,El'tsov
-
p. 1076 - 1087
(2007/10/03)
-
- Claisen orthoester rearrangement in the direct preparation of deplancheine derivatives possessing a malonyl group at C-15
-
The Claisen orthoester rearrangement utilizing allylic alcohols (1) and (2) , and triethyl ortho-2-ethoxycarbonylacetate (= ethyl triethyl orthomalonate) (4) leads directly to deplancheine derivatives (12 - 14) possessing a malonyl group at C-15. Compounds (12 - 14) represent the prototype of highly desired intermediates for the preparation of Corynanthe alkaloids and similar compounds.
- Lounasmaa, Mauri,Hanhinen, Pirjo
-
p. 1981 - 1989
(2007/10/03)
-
- Novel 2-amino-1,4-dihydropyridine calcium antagonists. I. Synthesis and antihypertensive effects of 2-amino-1,4-dihydropyridine derivatives having nitroxyalkoxycarbonyl groups at 3- and/or 5-position
-
Novel 2-amino-1,4-dihydropyridine derivatives, which contain nitroxy-alkoxycarbonyl groups at the 3- and/or 5-position, were synthesized and their pharmaceutical effect was evaluated in spontaneously hypertensive rats. The structure-activity relationships are discussed in terms of potency, onset-rapidity, and duration of antihypertensive activity. Remarkably prolonged duration of antihypertensive action was observed when a tertiary amino group was introduced on either side of an ester chain.
- Kobayashi,Inoue,Kita,Yoshiya,Nishino,Oizumi,Kimura
-
p. 788 - 796
(2007/10/02)
-
- Novel 2-amino-1,4-dihydropyridine calcium antagonists. II. Synthesis and antihypertensive effects of 2-amino-1,4-dihydropyridine derivatives having N,N-dialkylaminoalkoxycarbonyl groups at 3- and/or 5-positions
-
Novel 2-amino-1,4-dihydropyridine derivatives I, which contain N,N-dialkylaminoalkoxycarbonyl groups at the 3- and/or 5-position, were synthesized and their antihypertensive effects were evaluated in spontaneously hypertensive rats. Remarkably prolonged duration of antihypertensive action was observed when a tertiary amino group was introduced into either the 3- or 5-ester side-chain of the 1,4-dihydropyridine ring. In particular, the compounds containing cyclic amino moieties at the 3-position showed greater potency than those with acyclic amino moieties. Chemical modification studies indicated that the two ester side-chains of 1,4-dihydropyridine at the 3- and 5-position might function in a different manner in relation to the antihypertensive activities. 3-(1-Benzhydrylazetidin-3-yl) 5-isopropyl 2-amino-1,4-dihydro-6-methyl-4-(3-nitrophenyl)-3,5-pyridine-dicarboxyl ate, I-43 (CS-905), exhibited potent and long-lasting antihypertensive effects with gradual onset of action, and is a promising candidate as an antihypertensive drug.
- Kobayashi,Inoue,Nishino,Fujihara,Oizumi,Kimura
-
p. 797 - 817
(2007/10/02)
-
- Xanthine oxidase (XO): Relative configuration of complexes formed by the enzyme, 2- or 8-N-alkylhypoxanthines and 2-N-alkyl-8-azahypoxanthines. XII
-
Several 2- or 8-n-alkyl-hypoxanthines and a 2,8-di-n-pentylhypoxanthine were synthesized and tested as substrates or inhibitors of Xanthine Oxidase (XO). 8-Alkyl derivatives showed a substrate behaviour, whereas 2-alkyl substituted compounds were non-substrates and inhibitors. 2,8-di-n-pentylhypoxanthine was ineffective as inhibitor. The comparison between their activity allowed us to conclude that the complexes formed by the enzyme and the cited n-alkylhypoxanthines or 2-n -alkyl-8-azahypoxanthines involve their N(3) and N(9) positions in all the cases. The position of the n-alkyl chain determines the disposition of the molecule inside the complex: 2-n-alkyl-hypoxanthines and 2-n-alkyl-8-azahypoxanthines gave complexes with the same orientation of heterocyclic moieties, opposite that given by 8-n-alkyl-hypoxanthines.
- Biagi,Giorgi,Livi,Scartoni,Tonetti,Lucacchini
-
p. 357 - 374
(2007/10/02)
-
- HMG-COA REDUCTASE-INHIBITING SUBSTITUTED AMINO-PYRIDINES
-
HMG-COA reductase-inhibiting compounds of the formula STR1 in which X represents a group of the formula--CH 2--CH 2--or--CH=CH--,R represents a group of the formula STR2 R 1 represents optionally substituted aryl, R 2 represe
- -
-
-
- Studies on Amino Acid Derivatives. Part 7. General Method for the Synthesis of Penam and Cepham and Their Substituted Derivatives
-
Penam (7-oxo-4-thia-1-azabicycloheptane), a basic skeleton of penicillin-type β-lactams, has been synthesized as a stable compound from thiazolidinylacetic acid.The key step in this synthesis is the formation of the β-lactam ring by Mukaiyama-Ohno's procedure.Three methods are developed for the synthesis of thiazolidinylacetic acid from cysteamine by reactions with ethyl propiolate, ethyl ethoxycarbonylacetimidate, or t-butyl formylacetate.Using appropriate derivatives of the latter compounds, 5-, 6-, and 5,6-substituted derivatives of penam are also synthesized.The yields of the bicyclic β-lactams are shown to be strongly dependent upon the pattern of substituents on the thiazolidinylacetic acid.The synthesis of cephams using homocysteamine is also described.
- Chiba, Takuo,Sakaki, Jun-ichi,Takahashi, Takumi,Aoki, Kumi,Kamiyama, Akiko,et al.
-
p. 1845 - 1852
(2007/10/02)
-
- On the Origin of Nonexponential Fluorescence Decay in Tryptophan and Its Derivatives
-
The nonexponential fluorescence decay of tryptophan and its derivatives is discussed in terms of a simple model based on conformers about the Cα-Cβ bond and the relative rates of charge transfer from indole to various electrophiles.Accurate predictions concerning the relative fluorescence lifetimes and the form of the fluorescence decay law are made for tryptophan and 17 of its derivatives, including three new derivatives synthesized specifically to test the model.
- Petrich, J. W.,Chang, M. C.,McDonald, D. B.,Fleming, G. R.
-
p. 3824 - 3832
(2007/10/02)
-
- Method for producing isonitrosomalonic esters
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Isonitrosomalonic acid esters, which are useful as a starting material for synthesizing sweet peptides and other chemicals, are prepared by allowing a nitrosating agent to act on a corresponding alkyl alkoxycarbonyl acetoimidate.
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