- INHIBITORS OF ANTIGEN PRESENTATION BY HLA-DR
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Chromanone compounds, pharmaceutical compositions containing them, methods of making them, and methods of using them including methods for treating disease states, disorders, and conditions associated with the inhibition of antigen presentation by HLA-DR.
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Page/Page column 134
(2021/10/11)
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- Synthesis and antibacterial evaluation of new, unsymmetrical triaryl bisamidine compounds
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Herein we describe the synthesis and antibacterial evaluation of a new, unsymmetrical triaryl bisamidine compound series, [Am]-[indole]-[linker]-[HetAr/ Ar]-[Am], in which [Am] is an amidine or amino group, [linker] is a benzene, thiophene or pyridine ring, and [HetAr/Ar] is a benzimidazole, imidazopyridine, benzofuran, benzothiophene, pyrimidine or benzene ring. When the [HetAr/Ar] unit is a 5,6-bicyclic heterocycle, it is oriented such that the 5-membered ring portion is connected to the [linker] unit and the 6-membered ring portion is connected to the [Am] unit. Among the 34 compounds in this series, compounds with benzofuran as the [HetAr/Ar] unit showed the highest potencies. Introduction of a fluorine atom or a methyl group to the triaryl core led to the more potent analogs. Bisamidines are more active toward bacteria while the monoamidines are more active toward mammalian cells (as indicated by low CC 50 values). Importantly, we identified compound P12a (MBX 1887) with a relatively narrow spectrum against bacteria and a very high CC50 value. Compound P12a has been scaled up and is currently undergoing further evaluations for therapeutic applications.
- Nguyen, Son T.,Williams, John D.,Butler, Michelle M.,Ding, Xiaoyuan,Mills, Debra M.,Tashjian, Tommy F.,Panchal, Rekha G.,Weir, Susan K.,Moon, Chaeho,Kim, Hwa-Ok,Marsden, Jeremiah A.,Peet, Norton P.,Bowlin, Terry L.
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supporting information
p. 3366 - 3372
(2014/07/22)
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- Syntheses of benzo[b]furan-6-carbonitrile and 6-cyanobenzo[b]furan-2- boronic acid pinacol ester
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6-Cyanobenzo[b]furan-2-boronic acid pinacol ester (10) is a potentially useful two-point scaffold for the construction of specific compounds or compound libraries with benzofuran cores. Using a per-iodination/de-iodination strategy coupled with Sonogashir
- Williams, John D.,Ding, Xiaoyuan,Nguyen, Son,Vines, Kimberly K.,Peet, Norton P.
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p. 1974 - 1979
(2013/06/04)
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- Discovery of 4-(benzylaminomethylene)isoquinoline-1,3-(2H,4H)-diones and 4-[(pyridylmethyl)aminomethylene]isoquinoline-1,3-(2H,4H)-diones as potent and selective inhibitors of the cyclin-dependent kinase 4
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The series of 4-(benzylaminomethylene)isoquinoline-1,3-(2H,4H)-dione and 4-[(pyridylmethyl)aminometh-ylene]isoquinoline-1,3-(2H,4H)-dione derivatives reported here represents a novel class of potential antitumor agents, which potently and selectively inhibit CDK4 over CDK2 and CDK1. In the benzylamino headpiece, a 3-OH substituent is required on the phenyl ring for CDK4 inhibitory activity, which is further enhanced when an iodo, aryl, heteroaryl, t-butyl, or cyclopentyl substituent is introduced at the C-6 position of the isoquinoline-1,3-dione core. To circumvent the metabolic liability associated with the phenolic OH group on the 4-substituted 3-OH phenyl headpiece, we take two approaches: first, introduce a nitrogen o- or p- to the 3-OH group in the phenyl ring; second, replace the phenyl headpiece with N-substituted 2-pyridones. We present here the synthesis, SAR data, metabolic stability data, and a CDK4 mimic model that explains the binding, potency, and selectivity of our CDK4 selective inhibitors.
- Tsou,Liu, Xiaoxiang,Birnberg, Gary,Kaplan, Joshua,Otteng, Mercy,Tran, Tritin,Kutterer, Kristina,Tang, Zhilian,Suayan, Ron,Zask, Arie,Ravi, Malini,Bretz, Angela,Grillo, Mary,Mcginnis, John P.,Rabindran, Sridhar K.,Ayral-Kaloustian, Semiramis,Mansour, Tarek S.
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scheme or table
p. 2289 - 2310
(2010/02/28)
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- AMIDINOPHENYLPYRUVIC ACID DERIVATIVES
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An amidinophenylpyruvic acid derivative of the following formula, analogs thereof and pharmaceutically acceptable salts thereof have an excellent antagonistic effect against activated blood coagulation factor VII.
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- Rational design, synthesis, and structure-activity relationships of novel factor Xa inhibitors: (2-substituted-4-amidinophenyl)pyruvic and -propionic acids
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An inhibitor of factor Xa (fXa), the m-substituted benzamidine AXC1578 (1a), was structurally modified with the aim of increasing its potency. In particular, pyruvic acid and propionic acid substituents were incorporated into the P1 benzamidine moiety to
- Sagi, Kazuyuki,Nakagawa, Tadakiyo,Yamanashi, Masahiro,Makino, Shingo,Takahashi, Mitsuo,Takayanagi, Masaru,Takenaka, Kaoru,Suzuki, Nobuyasu,Oono, Seiji,Kataoka, Noriyasu,Ishikawa, Kohki,Shima, Sayaka,Fukuda, Yumiko,Kayahara, Takashi,Takehana, Shunji,Shima, Yoichiro,Tashiro, Kazumi,Yamamoto, Hiroshi,Yoshimoto, Ryota,Iwata, Seinosuke,Tsuji, Takashi,Sakurai, Kuniya,Shoji, Masataka
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p. 1845 - 1857
(2007/10/03)
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- BENZAMIDINE DERIVATIVES
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A benzamidine derivative of the following formula, analogs thereof and pharmaceutically acceptable salts thereof have an effect of inhibiting the blood coagulation based on their excellent effect of inhibiting activated blood-coagulation factor X. Thus, a blood-coagulation inhibitor or an agent for preventing or treating thrombosis or embolism, containing one of those compounds as the active ingredient, is provided.
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- Benzamidine derivatives
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Benzamidine derivatives of the following formula, analogs thereof and pharmaceutically acceptable salts thereof are provided. These compounds have an effect of inhibiting activated blood-coagulation factor X, and they are useful as agents for preventing or treating various diseases caused by thrombi or emboli.
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- BENZAMIDINE DERIVATIVES
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Benzamidine derivatives of the following formulae or analogs thereof, i. e., pharmaceutically acceptable salts thereof, are provided. These compounds or salts thereof have a blood-coagulation inhibiting effect based on an excellent effect of inhibiting the action of activated blood coagulation factor X, and they are useful as anticoagulants.
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