- Synthesis of pyrimido[2,1-a]isoindolone and isoindolo[2,1-a]quinazolinoneviaintramolecular aza-Prins type reaction
-
A novel aza-Prins type cyclization reaction involvingN-acyliminium ions and amides is reported for the synthesis of tetrahydropyrimido[2,1-a]isoindole-2,6-dione and 6,6a-dihydroisoindolo[2,1-a]quinazoline-5,11-dione derivatives in excellent yields. The strategy features inexpensive reagents, mild reaction conditions, and metal-free synthesis of N-heterocyclic frameworks. Further, post-synthetic modification results in the unprecedented formation of its triazole, tetracyclic diazacyclopenta[def]phenanthrene-1,4(9a1H)-dione and carbonyl derivatives.
- Biswas, Subhamoy,Porashar, Bikoshita,Arandhara, Pallav Jyoti,Saikia, Anil K.
-
supporting information
p. 11701 - 11704
(2021/11/12)
-
- Arylamide as Potential Selective Inhibitor for Matrix Metalloproteinase 9 (MMP9): Design, Synthesis, Biological Evaluation, and Molecular Modeling
-
Previous studies have reported that compounds bearing an arylamide linked to a heterocyclic planar ring have successfully inhibited the hemopexin-like domain (PEX9) of matrix metalloproteinase 9 (MMP9). PEX9 has been suggested to be more selectively targe
- Al-Najjar, Belal,Dewa, Sangga P.,Hariono, Maywan,Jati, Benedictus W.,Jenie, Riris I.,Julianus, Jeffry,Nugroho, Ervan S.,Nuwarda, Rina F.,Putra, Kevin C.,Qodria, Lailatul,Ramadani, Ratna D.,Rollando, Rollando,Tiara, Reynaldo,Wahab, Habibah A.,Wisnumurti, Yohanes K.,Yusuf, Muhammad
-
-
- BENZAMIDE DERIVATIVES COMPOUNDS AND THEIR USE AS UREASE INHIBITORS
-
The present invention relates to a liquid crystal display device. A benzamide derivative compound, or a pharmaceutically acceptable salt thereof, is provided. The benzamide derivative compound or a pharmaceutically acceptable salt thereof according to the present invention shows excellent effects on the treatment and prevention of various diseases such as gastric ulcer, gastric cancer, gastric lymphoma, gastric cancer, urinary tract, and nephritis.
- -
-
Paragraph 0029-0030; 0087; 0092
(2021/02/12)
-
- Synthesis of new tricyclic 5,6-dihydro-4H-benzo[b][1,2,4]tri-azolo[1,5-d][1,4]diazepine derivatives by [3+ + 2]-cyclo-addition/rearrangement reactions
-
Two new series of tricyclic heterocycles, namely 5,6-dihydro-4H-benzo[b][1,2,4]triazolo[1,5-d][1,4]diazepinium salts 10 and the related neutral, free bases 13 were synthesized from 4-acetoxy-1-acetyl-4-phenylazo-1,2,3,4-tetrahydroquinolines 8 and nitriles 9 in the presence of aluminium chloride by the [3+ + 2]-cycloaddition reaction of the in situ generated azocarbenium intermediates 14 followed by a ring-expansion rearrangement. In the rearrangement reaction, the phenyl substituent in the initially formed spiro-triazolium adducts 16 underwent a [1,2]-migration from C(3) to the electron-deficient N(2). This led to the ring expansion from 6-membered piperidine to 7-membered diazepine furnishing the tricyclic 1,2,4-triazole-fused 1,4-benzodiazepines.
- Luan, Lin-bo,Song, Zi-jie,Li, Zhi-ming,Wang, Quan-rui
-
supporting information
p. 1826 - 1833
(2018/08/21)
-
- Synthesis and structure-activity relationships of LP1 derivatives: N-methyl-N-phenylethylamino analogues as novel MOR agonists
-
The opioid pharmacological profile of cis-(-)-N-normetazocine derivatives is deeply affected by the nature of their N-substituents. Here, our efforts were focused on the synthesis and pharmacological evaluation of novel derivatives of the lead LP1, a multitarget opioid analgesic compound featuring an N-phenylpropanamido substituent. LP1 derivatives 5a-d and 6a-d were characterized by flexible groups at the N-substituent that allow them to reposition themselves relative to cis-(-)-N-normetazocine nucleus, thus producing different pharmacological profiles at the mu, delta and kappa opioid receptors (MOR, DOR and KOR) in in vitro and in vivo assays. Among the series, compound 5c, with the best in vitro and in vivo profile, resulted a MOR agonist which displays a KiMOR of 6.1 nM in a competitive binding assay, and an IC50 value of 11.5 nM and an Imax of 72% in measurement of cAMP accumulation in HEK293 cells stably expressing MOR, with a slight lower efficacy than LP1. Moreover, in a mouse model of acute thermal nociception, compound 5c, intraperitoneally administered, exhibits naloxone-reversed antinociceptive properties with an ED50 of 4.33 mg/kg. These results expand our understanding of the importance of N-substituent structural variations in the opioid receptor profile of cis-(-)-N-normetazocine derivatives and identify a new MOR agonist useful for the development of novel opioid analgesics for pain treatment.
- Turnaturi, Rita,Parenti, Carmela,Prezzavento, Orazio,Marrazzo, Agostino,Pallaki, Paschalina,Georgoussi, Zafiroula,Amata, Emanuele,Pasquinucci, Lorella
-
-
- Synthesis, in vitro and in silico studies of novel potent urease inhibitors: N-[4-({5-[(3-Un/substituted-anilino-3-oxopropyl)sulfanyl]-1,3,4-oxadiazol-2-yl}methyl)-1,3-thiazol-2-yl]benzamides
-
The present article describes the synthesis, in vitro urease inhibition and in silico molecular docking studies of a novel series of bi-heterocyclic bi-amides. The synthesis of title compounds was initiated by benzoylation, with benzoyl chloride (1), of the key starter ethyl 2-(2-amino-1,3-thiazol-4-yl)acetate (2) in weak basic aqueous medium followed by hydrazide formation, 4, and cyclization with CS2 to reach the parent bi-heterocyclic nucleophile, N-{4-[(5-sulfanyl-1,3,4-oxadiazol-2-yl)methyl]-1,3-thiazol-2-yl}benzamide (5). Various electrophiles, 8a–l, were synthesized by a two-step process and these were finally coupled with 5 to yield the targeted bi-heterocyclic bi-amide molecules, 9a–l. The structures of the newly synthesized products were corroborated by IR, 1H NMR, 13C NMR, EI-MS and elemental analysis. The in vitro screening of these molecules against urease explored that most of the compounds exhibit potent inhibitory potential against this enzyme. The compound 9j, with IC50 value of 2.58 ± 0.02 μM, exhibited most promising inhibitory activity among the series, relative to standard thiourea having IC50 value of 21.11 ± 0.12 μM. In silico studies fully augmented the experimental enzyme inhibition results. Chemo-informatics analysis showed that synthesized compounds (9a–l) mostly obeyed the Lipinski's rule. Molecular docking study suggested that ligand 9j exhibited good binding energy value (?7.10 kcal/mol) and binds within the active region of target protein. So, on the basis of present investigation, it was inferred that 9j may serve as a novel scaffold for designing more potent urease inhibitors.
- Abbasi, Muhammad Athar,Hassan, Mubashir,Aziz-ur-Rehman,Siddiqui, Sabahat Zahra,Raza, Hussain,Shah, Syed Adnan Ali,Seo, Sung-Yum
-
p. 3791 - 3804
(2018/06/14)
-
- Asymmetric Synthesis of Cyclopentene-Fused Tetrahydroquinolines via N-Heterocyclic Carbene Catalyzed Domino Reactions
-
A new strategy for the N-heterocyclic carbene catalyzed asymmetric synthesis of cyclopentene-fused tetrahydroquinoline derivatives has been developed. The one-pot organocatalytic domino protocol allows a direct entry to the characteristic cyclopenta[ c ]tetrahydroquinoline core of many alkaloids and some potential drugs employing readily available quinolinone and enal substrates in good domino yields and stereoselectivities.
- Zhao, Long,Li, Sun,Wang, Lei,Yu, Shun,Raabe, Gerhard,Enders, Dieter
-
p. 2523 - 2532
(2018/05/28)
-
- Ruthenium-Pincer-Catalyzed Hydrogenation of Lactams to Amino Alcohols
-
By using the commercially available ruthenium pincer complex (Ru-MACHO-BH) as a catalyst, the challenging direct hydrogenation of lactams and analogues has been successfully accomplished to deliver corresponding value-added amino alcohols in good-to-excellent yields under mild reaction conditions. Remarkably, in addition to N-protected lactams, unprotected ones could also be readily reduced in the presence of a catalytic amount of weak base or even under neutral reaction conditions, which further highlights the broad substrate scope and the protocol efficiency.
- Chen, Jiangbo,Wang, Jiaquan,Tu, Tao
-
p. 2559 - 2565
(2018/07/30)
-
- Hydroxamic acid derivative and JHDM inhibitor
-
PROBLEM TO BE SOLVED: To provide a compound capable of selectively inhibiting the function of JHDM, and a JHDM inhibitor. SOLUTION: This hydroxamic acid derivative expressed by formula (1a) [wherein, R1and R2are each independently alkyl which may have a branch; and (n) is an integer of ≥1] or general formula (1b) [wherein, ring X is a 3 to 8-membered saturated carbon ring; and (n) is an integer of ≥1], its pharmaceutically acceptable salt, hydrate, solvate or prodrug is provided. COPYRIGHT: (C)2011,JPOandINPIT
- -
-
Paragraph 0139
(2016/10/09)
-
- Quinol derivatives as potential trypanocidal agents
-
Quinols have been developed as a class of potential anti-cancer compounds. They are thought to act as double Michael acceptors, forming two covalent bonds to their target protein(s). Quinols have also been shown to have activity against the parasite Trypa
- Capes, Amy,Patterson, Stephen,Wyllie, Susan,Hallyburton, Irene,Collie, Iain T.,McCarroll, Andrew J.,Stevens, Malcolm F.G.,Frearson, Julie A.,Wyatt, Paul G.,Fairlamb, Alan H.,Gilbert, Ian H.
-
experimental part
p. 1607 - 1615
(2012/04/23)
-
- Formation of acridones by ethylene extrusion in the reaction of arynes with β-lactams and dihydroquinolinones
-
N-Unsubstituted β-lactams react with a molecule of aryne by insertion into the amide bond to form a 2,3-dihydroquinolin-4-one, which subsequently reacts with another molecule of aryne to form an acridone by extrusion of a molecule of ethylene. 2,3-Dihydroquinolin-4-ones react under the same reaction conditions to afford identical results. This is the first example of ethylene extrusion in aryne chemistry.
- Fang, Yuesi,Rogness, Donald C.,Larock, Richard C.,Shi, Feng
-
experimental part
p. 6262 - 6270
(2012/09/22)
-
- Design, synthesis and biological evaluation of hydroxamic acid derivatives as potential high density lipoprotein (HDL) receptor CLA-1 up-regulating agents
-
Trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA) were reported in our recent publication as novel human high density lipoprotein (HDL) receptor CD36 and Lysosomal integral membrane protein-II Analogous-1 (CLA-1) up-regulators. As part of a
- Chen, Xiaofang,Wang, Li,Du, Yu,Wu, Yanbin,Jia, Xiaojian,Yang, Yuan,Hong, Bin
-
experimental part
p. 9178 - 9193
(2012/01/12)
-
- Synthesis and biological evaluation of 1-substituted-3(5)-(6-methylpyridin- 2-yl)-4-(quinolin-6-yl)pyrazoles as transforming growth factor-β type 1 receptor kinase inhibitors
-
A series of 1-substituted-3(5)-(6-methylpyridin-2-yl)-4-(quinolin-6-yl) pyrazoles 14a-e, 15a-e, 17a-c, and 18a-d have been synthesized and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. The 6
- Jin, Cheng Hua,Krishnaiah, Maddeboina,Sreenu, Domalapally,Rao, Kota Sudhakar,Subrahmanyam, Vura Bala,Park, Chul-Yong,Son, Jee-Yeon,Sheen, Yhun Yhong,Kim, Dae-Kee
-
body text
p. 2633 - 2640
(2011/06/11)
-
- Synthesis and biological evaluation of 1-substituted-3(5)-(6-methylpyridin- 2-yl)-4-(quinoxalin-6-yl)pyrazoles as transforming growth factor-β type 1 receptor kinase inhibitors
-
A series of 1-substituted-3(5)-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl) pyrazoles 14a-d, 15a-d, 17a, 17b, 18a-d, 19a, and 19b has been synthesized and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporte
- Jin, Cheng Hua,Sreenu, Domalapally,Krishnaiah, Maddeboina,Subrahmanyam, Vura Bala,Rao, Kota Sudhakar,Nagendra Mohan, Annaji Venkata,Park, Chul-Yong,Son, Jee-Yeon,Son, Do-Hyun,Park, Hyun-Ju,Sheen, Yhun Yhong,Kim, Dae-Kee
-
scheme or table
p. 3917 - 3925
(2011/11/07)
-
- Chroman and tetrahydroquinoline ureas as potent TRPV1 antagonists
-
Novel chroman and tetrahydroquinoline ureas were synthesized and evaluated for their activity as TRPV1 antagonists. It was found that aryl substituents on the 7- or 8-position of both bicyclic scaffolds imparted the best in vitro potency at TRPV1. The most potent chroman ureas were assessed in chronic and acute pain models, and compounds with the ability to cross the blood-brain barrier were shown to be highly efficacious. The tetrahydroquinoline ureas were found to be potent CYP3A4 inhibitors, but replacement of bulky substituents at the nitrogen atom of the tetrahydroisoquinoline moiety with small groups such as methyl can minimize the inhibition.
- Schmidt, Robert G.,Bayburt, Erol K.,Latshaw, Steven P.,Koenig, John R.,Daanen, Jerome F.,McDonald, Heath A.,Bianchi, Bruce R.,Zhong, Chengmin,Joshi, Shailen,Honore, Prisca,Marsh, Kennan C.,Lee, Chih-Hung,Faltynek, Connie R.,Gomtsyan, Arthur
-
scheme or table
p. 1338 - 1341
(2011/04/23)
-
- Evaluation of N-substitution in 6,7-benzomorphan compounds
-
6,7-Benzomorphan derivatives, exhibiting different μ, δ, and κ receptor selectivity profiles depending on the N-substituent, represent a useful skeleton for the synthesis of new and better analgesic agents. In this work, an aromatic ring and/or alkyl residues have been used with an N-propanamide or N-acetamide spacer for the synthesis of a new series of 5,9-dimethyl-2′-hydroxy-6,7-benzomorphan derivatives (12-22). Data obtained by competition binding assays showed that the μ opioid receptor seems to prefer an interaction with the 6,7-benzomorphan ligands having an N-substituent with a propanamide spacer and less hindered amide. Highly stringent features are required for δ receptor interaction, while an N-acetamide spacer and/or bulkier amide could preferentially lead to κ receptor selectivity. In the propanamide series, compound 12 (named LP1) displayed high μ affinity (Ki = 0.83 nM), good δ affinity (Ki = 29 nM) and low affinity for the κ receptor (Ki = 110 nM), with a selectivity ratio δ/μ and κ/μ of 35.1 and 132.5, respectively. Further, in the adenylyl cyclase assay, LP1 displayed a μ/δ agonist profile, with IC50 values of 4.8 and 12 nM at the μ and δ receptors, respectively. The antinociceptive potency of LP1 in the tail-flick test after sc administration in rat was comparable with the potency of morphine (ED50 = 2.03 and 2.7 mg/kg, respectively), and was totally reversed by naloxone. LP1, possessing a μ/δ agonist profile, could represent a lead in further developing benzomorphan-based ligands with potent in vivo analgesic activity and a reduced tendency to induce side effects.
- Pasquinucci, Lorella,Prezzavento, Orazio,Marrazzo, Agostino,Amata, Emanuele,Ronsisvalle, Simone,Georgoussi, Zafiroula,Fourla, Danai-Dionysia,Scoto, Giovanna M.,Parenti, Carmela,Arico, Giuseppina,Ronsisvalle, Giuseppe
-
experimental part
p. 4975 - 4982
(2010/09/08)
-
- Synthesis and biological evaluation of a new series of berberine derivatives as dual inhibitors of acetylcholinesterase and butyrylcholinesterase
-
A series of novel berberine derivatives were designed, synthesized, and biologically evaluated as inhibitors of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Among these derivatives, compound 48a, berberine linked with 3-methylpyridi
- Huang, Ling,Luo, Zonghua,He, Feng,Lu, Jing,Li, Xingshu
-
experimental part
p. 4475 - 4484
(2010/08/22)
-
- Targeting mycobacterium protein tyrosine phosphatase B for antituberculosis agents
-
Protein tyrosine phosphatases are often exploited and subverted by pathogenic bacteria to cause human diseases. The tyrosine phosphatase mPTPB from Mycobacterium tuberculosis is an essential virulence factor that is secreted by the bacterium into the cytoplasm of macrophages, where it mediates mycobacterial survival in the host. Consequently, there is considerable interest in understanding the mechanism by which mPTPB evades the host immune responses, and in developing potent and selective mPTPB inhibitors as unique antituberculosis (antiTB) agents. We uncovered that mPTPB subverts the innate immune responses by blocking the ERK1/2 and p38 mediated IL-6 production and promoting host cell survival by activating the Akt pathway. We identified a potent and selective mPTPB inhibitor I-A09 with highly efficacious cellular activity, from a combinatorial library of bidentate benzofuran salicylic acid derivatives assembled by click chemistry. We demonstrated that inhibition of mPTPB with I-A09 in macrophages reverses the altered host immune responses induced by the bacterial phosphatase and prevents TB growth in host cells. The results provide the necessary proof-of-principle data to support the notion that specific inhibitors of the mPTPB may serve as effective antiTB therapeutics.
- Zhou, Bo,He, Yantao,Zhang, Xian,Xu, Jie,Luo, Yong,Wang, Yuehong,Franzblau, Scott G.,Yang, Zhenyun,Chan, Rebecca J.,Liu, Yan,Zheng, Jianyu,Zhang, Zhong-Yin
-
scheme or table
p. 4573 - 4578
(2010/10/03)
-
- Derivatives of salicylic acid as inhibitors of YopH in yersinia pestis
-
Yersinia pestis causes diseases ranging from gastrointestinal syndromes to bubonic plague and could be misused as a biological weapon. As its protein tyrosine phosphatase YopH has already been demonstrated as a potential drug target, we have developed two series of forty salicylic acid derivatives and found sixteen to have micromolar inhibitory activity. We designed these ligands to have two chemical moieties connected by a flexible hydrocarbon linker to target two pockets in the active site of the protein to achieve binding affinity and selectivity. One moiety possessed the salicylic acid core intending to target the phosphotyrosine-binding pocket. The other moiety contained different chemical fragments meant to target a nearby secondary pocket. The two series of compounds differed by having hydrocarbon linkers with different lengths. Before experimental co-crystal structures are available, we have performed molecular docking to predict how these compounds might bind to the protein and to generate structural models for performing binding affinity calculation to aid future optimization of these series of compounds.
- Huang, Zunnan,He, Yantao,Zhang, Xian,Gunawan, Andrea,Wu, Li,Zhang, Zhong-Yin,Wong, Chung F.
-
scheme or table
p. 85 - 99
(2011/03/19)
-
- Synthesis of substituted 2-amino-5,6-dihydropyrimidin-4-ones using an aza-Wittig reaction
-
An aza-Wittig reaction has been used for the first time in the synthesis of substituted 2-amino-5,6-dihydropyrimidin-4-ones via condensation of triphenyliminophosphoranes with aromatic heterocumulenes (arylisocyanates and thiocyanates).
- Kochubey,Blochin,Rodin,Perevalov
-
p. 897 - 900
(2008/02/10)
-
- Rapid assembly and in situ screening of bidentate inhibitors of protein tyrosine phosphatases
-
We have successfully designed and synthesized a small library of protein tyrosine phosphatase (PTP) inhibitors, in which the so-called "click chemistry" or Cu(I)-catalyzed 1,3-dipolar alkyne-azide coupling reaction was carried out for rapid assembly of 66 different bidentate compounds. Subsequent in situ enzymatic screening revealed a potential PTP1B inhibitor (IC50 = 4.7 μM) which is 10-100 fold more potent than other PTPs.
- Srinivasan, Rajavel,Uttamchandani, Mahesh,Yao, Shao Q.
-
p. 713 - 716
(2007/10/03)
-
- Synthesis, biological evaluation, and quantitative structure. A new class of potent H1 antagonists
-
Some [β-(Aroylamino)ethyl]piperazines and -piperidines and [2-[(Arylamino)carbonyl]ethyl]piperazines, -piperidines, -pyrazinopyridoindoles, and -pyrazinoisoquinolines have been synthesized and their H1-antagonistic activity studied in isolated guinea pig
- Saxena,Agarwal,Patnaik,Saxena
-
p. 2970 - 2976
(2007/10/02)
-
- A Convenient Synthesis of Monocyclic β-Lactams by Means of Solid-Liquid Phase Transfer Reactions
-
The intramolecular N-alkylation of β-bromopropionamides (1) under phase transfer conditions afforded monocyclic N-substituted β-lactams (2) in high yields.In a similar manner, cyclization by N1-C4 bond formation gave 4-benzoyl-2-azet
- Takahata, Hiroki,Ohnishi, Yoshinori,Takehara, Hiroyuki,Tsuritani, Kazuko,Yamazaki, Takao
-
p. 1063 - 1068
(2007/10/02)
-
- Synthesis and evaluation of novel alkylpiperazines as potential dopamine antagonists
-
Several alkylpiperazines, monocyclic subfragments of known tricyclic neuroleptic agents, were evaluated as dopamine antagonists in the isolated rabbit ear artery preparation. Compounds prepared and evaluated are of the general structure Ar-X-(CH2)(n)-Y, where X = C, O, and N, n = 1-3, and Y, for the most part, was 4-methylpiperazine. Those compounds where X = NH, n = 3, and X = (Z)-CH=CH, n = 2, with an electron-witdrawing group meta to the side chain, possess dopamine antagonist activity comparable to that of clozapine. It is concluded that the entire tricyclic structure of phenothiazine-like agents (or at least more than a monocyclic ring system) is necessary for optimal activity as a dopamine antagonist in the receptor preparation used in this study.
- Glennon,Salley Jr.,Steinsland,Nelson
-
p. 678 - 683
(2007/10/02)
-