- Access to 2-pyridinylamide and imidazopyridine from 2-fluoropyridine and amidine hydrochloride
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Under catalyst-free conditions, an efficient method to synthesize 2-pyridinylamides has been developed, and the protocol uses inexpensive and readily available 2-fluoropyridine and amidine derivatives as the starting materials. Simultaneously, the copper-catalysed approach to imidazopyridine derivatives has been established with high chemoselectivity and regiospecificity. The results suggest that the nitrogen-heterocycles containing iodide substituents can also be compatible for the reaction via the cascade Ullmann-type coupling, and the nucleophilic substitution reaction provides the target products in a one-pot manner.
- Chen, Lu,Huang, Shuo,Ji, Xiaoliang,Li, Jiaming,Li, Jian,Li, Yibiao,Liu, Jiasheng,Peng, Shiyong,Zhang, Kun
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supporting information
p. 9292 - 9299
(2020/12/03)
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- Design, Synthesis, and Evaluation of the Highly Selective and Potent G-Protein-Coupled Receptor Kinase 2 (GRK2) Inhibitor for the Potential Treatment of Heart Failure
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A novel class of therapeutic drug candidates for heart failure, highly potent and selective GRK2 inhibitors, exhibit potentiation of β-adrenergic signaling in vitro studies. Hydrazone derivative 5 and 1,2,4-triazole derivative 24a were identified as hit compounds by HTS. New scaffold generation and SAR studies of all parts resulted in a 4-methyl-1,2,4-triazole derivative with an N-benzylcarboxamide moiety with highly potent activity toward GRK2 and selectivity over other kinases. In terms of subtype selectivity, these compounds showed enough selectivity against GRK1, 5, 6, and 7 with almost equipotent inhibition to GRK3. Our medicinal chemistry efforts led to the discovery of 115h (GRK2 IC50 = 18 nM), which was obtained the cocrystal structure with human GRK2 and an inhibitor of GRK2 that potentiates β-adrenergic receptor (βAR)-mediated cAMP accumulation and prevents internalization of βARs in β2AR-expressing HEK293 cells treated with isoproterenol. Therefore, 115h appears to be a novel class of therapeutic for heart failure treatment.
- Okawa, Tomohiro,Aramaki, Yoshio,Yamamoto, Mitsuo,Kobayashi, Toshitake,Fukumoto, Shoji,Toyoda, Yukio,Henta, Tsutomu,Hata, Akito,Ikeda, Shota,Kaneko, Manami,Hoffman, Isaac D.,Sang, Bi-Ching,Zou, Hua,Kawamoto, Tetsuji
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p. 6942 - 6990
(2017/09/07)
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- Preparation of the HIV Attachment Inhibitor BMS-663068. Part 1. Evolution of Enabling Strategies
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The development of two enabling routes that led to the production of >1000 kg of BMS-663068 (3) is described. The route identified for the initial 100 kg delivery to support development activities and initial clinical trials involved the conversion of 2-amino-4-picoline to the parent active pharmaceutical ingredient (API), followed by pro-drug installation and deprotection. To eliminate the problematic isolation of the parent API and synthesis of di-t-butyl(chloromethyl)phosphate, a second-generation pro-drug installation route was developed which involved the conversion of a late-stage common intermediate to an N(1)-thioether derivative followed by chloromethylation, displacement with di-t-butylpotassium phosphate, and deprotection. This second strategy resulted in the multikilogram scale preparation of the API in 14 linear steps and ~7% overall yield.
- Fox, Richard J.,Tripp, Jonathan C.,Schultz, Mitchell J.,Payack, Joseph F.,Fanfair, Dayne D.,Mudryk, Boguslaw M.,Murugesan, Saravanababu,Chen, Chung-Pin H.,La Cruz, Thomas E.,Ivy, Sabrina E.,Broxer, Sévrine,Cullen, Ryan,Erdemir, Deniz,Geng, Peng,Xu, Zhongmin,Fritz, Alan,Doubleday, Wendel W.,Conlon, David A.
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p. 1095 - 1109
(2017/08/23)
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- Preparation method of 2-aminopyridine-4-methanol medical intermediate
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The invention discloses a preparation method of a 2-aminopyridine-4-methanol medical intermediate. By virtue of the preparation method, the 2-aminopyridine-4-methanol medical intermediate is prepared from 2-aminopyridine-4-methyl sequentially through acet
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Paragraph 0021; 0023
(2017/01/12)
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- The first vinyl acetate mediated organocatalytic transesterification of phenols: A step towards sustainability
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The present report outlines our efforts toward a simple yet elegant protocol for O-acylation of a wide variety of phenols. This highly enabling and solventless method relies on vinyl acetate as an innocuous acyl donor and DABCO as an organocatalyst. Operational simplicity, excellent yields, higher and faster conversion rates without excess reagents, a simple workup and essentially no need of columns are some of the salient features of the reported protocol.
- Kumar, Manoj,Bagchi, Sourav,Sharma, Anuj
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p. 8329 - 8336
(2015/11/10)
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- DEUTERIUM-ENRICHED HETEROCYCLIC COMPOUNDS AS KINASE INHIBITORS
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The present invention provides deuterium-enriched heteroaryl-containing urea compounds (I) and use of the same for treating conditions mediated by protein kinase such as
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Page/Page column 45
(2012/03/26)
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- PYRIDYLAMIDINE COMPOUND OR SALT THEREOF, AND AGRICULTURAL OR HORTICULTURAL FUNGICIDE COMPOSITION CONTAINING THE SAME AS ACTIVE INGREDIENT
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An agricultural or horticultural fungicide composition having stabilized high plant disease control effect is provided. The agricultural or horticultural fungicide composition contains a pyridylamidine compound represented by the formula (I): or a salt th
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Page/Page column 15
(2009/09/04)
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- Imidazole compounds having an antiinflammatory effect
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The invention relates to 2-sulfinyl- or 2-sulfonyl-substituted imidazole derivatives of the formula I in which the radicals R1, R2, R3 and R4 have the meaning indicated in the description. The compounds of the i
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Page/Page column 14; 41
(2008/06/13)
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- Synthesis of (aryloxyacetylamino)-isonicotinic/nicotinic acid analogues as potent hypoxia-inducible factor (HIF)-1α inhibitors
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We report a new series of HIF-1α inhibitors which were obtained through structural modifications of previously reported lead 1. The in vitro inhibitory potencies of newly synthesized compounds were evaluated against hypoxia-induced HIF-1 activation using
- Boovanahalli, Shanthaveerappa K.,Jin, Xuejun,Jin, Yinglan,Kim, Jin Hwan,Dat, Nguyen Tien,Hong, Young-Soo,Lee, Jeong Hyung,Jung, Sang-Hun,Lee, Kyeong,Lee, Jung Joon
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p. 6305 - 6310
(2008/09/17)
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- 2-SULFINYL- AND 2-SULFONYL-SUBSTITUTED IMIDAZOLE DERIVATIVES AND THEIR USE AS CYTOKINE INHIBITORS
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The invention relates to 2-sulfinyl- or 2-sulfonyl-substituted imidazole derivatives of the formula (I) in which the radicals R1, R2, R3 and R4 have the meaning indicated in the description. The compounds of the
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Page/Page column 25
(2008/06/13)
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- MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 5: Carbon-substituted analogues at the C-2 position
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A series of 4-oxo-4H-pyrido[1,2-a]pyrimidine derivatives, derivatized at the 2-position with carbon-linked substituents, were synthesized and evaluated for their ability to potentiate the activity of the fluoroquinolone levofloxacin (LVFX) and the anti-pseudomonas β-lactam aztreonam (AZT) in Pseudomonas aeruginosa. Palladium-catalyzed cross-coupling methods were applied for the incorporation of aliphatic and aromatic substituents.
- Yoshida, Ken-Ichi,Nakayama, Kiyoshi,Kuru, Noriko,Kobayashi, Shozo,Ohtsuka, Masami,Takemura, Makoto,Hoshino, Kazuki,Kanda, Hiroko,Zhang, Jason Z.,Lee, Ving J.,Watkins, William J.
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p. 1993 - 2004
(2007/10/03)
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- Synthesis and SAR of 2-(4-fluorophenyl)-3-pyrimidin-4-ylimidazo[1,2-a]pyridine derivatives as anticoccidial agents
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Compounds 10a-10d and 10i are very potent inhibitors of Eimeria tenella cGMP-dependent protein kinase (0.081-0.32 nM) and are very efficacious antiparasitic agents in vivo when administered to chickens at 12.5-25 ppm levels in the feed.
- Feng, Dennis,Fisher, Michael,Liang, Gui-Bai,Qian, Xiaoxia,Brown, Chris,Gurnett, Anne,Leavitt, Penny Sue,Liberator, Paul A.,Mathew, John,Misura, Andrew,Samaras, Samantha,Tamas, Tamas,Schmatz, Dennis M.,Wyvratt, Matthew,Biftu, Tesfaye
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p. 5978 - 5981
(2007/10/03)
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- A novel three-component reaction of N-fluoropyridinium salts: A facile approach to imidazo[1,2-a]pyridines
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The reaction of N-fluoropyridinium triflate with isonitriles in acetonitrile and propionitrile in the presence of NaBH(OAc)3 led to the formation of the corresponding imidazo[1,2-a]pyridines in 44-73% yields. The proposed reaction mechanism involves the intermediate formation of a highly reactive carbene species and apparent reduction of the pyridinium intermediate with NaBH(OAc)3 to yield the targeted heterocycles.
- Kiselyov, Alexander S.
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p. 4487 - 4490
(2007/10/03)
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- AZOLECARBOXAMIDE HERBICIDES
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Compounds of Formula (I), and their N-oxides and agriculturally suitable salts, are disclosed which are useful for controlling undesired vegetation, wherein J is (J-1), (J-2,(J-3), (J-4), (J-5), (J-6), (J-7), (J-8) and R1a, R1b, R1c, R2a, R2b, R3, R4, R05, T, U, W, Y and Z are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula (I) and a method for controlling undesired vegetation which involves contacting the vegetation or its environment with an effective amount of a compound of Formula (I). Also disclosed are mixtures and compositions comprising a herbicidally effective amount of a compound of Formula (Iz) wherein J, R1a, R1b, R1c, R2a, R2b, R3, R4, R05, T, U, W, Y and Z are as defined in the disclosure; and an effective amount of another herbicide or herbicide safener. Also disclosed is a method for selectively controlling undesired vegetation in a crop that involves contacting the locus of a crop with an effective amount of a compound of Formula (Iz) and a effective amount of a safener.
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- Identification of regioisomers in a series of N-substituted pyridin-4-yl imidazole derivatives by regiospecific synthesis, GC/MS, and 1H NMR
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The regiospecific synthesis of 2a (Scheme 3), a novel and potent pyridinyl imidazole inhibitor of p38 MAP (mitogen-activated protein) kinase, and the regioselective preparation of its regioisomer 2b (Scheme 4) are described. Chromatographic and spectroscopic data are presented, which in this class of compounds allow the unambiguous identification of regioisomers prepared by a nonregiospecific synthetic strategy. Biological data demonstrating the importance of the correct regiochemistry for inhibition of p38 are given.
- Wagner, Gerd K.,Kotschenreuther, Dunja,Zimmermann, Werner,Laufer, Stefan A.
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p. 4527 - 4530
(2007/10/03)
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- Synthesis and crystal structure of dichloro{bis [N-(4-methyl-2-pyridinyl)acetamide]} copper (II)
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Dichlorobis[N-(4-methyl-2-pyridinyl)acetamide] copper (11) was prepared and its structure was first resolved by X-ray analysis.
- Zhang, Wen,Leng, Xuebing,Sun, Wen-Hua
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p. 808 - 809
(2007/10/03)
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- Carboxamidation of pyridines by the system of elemental fluorine- carbonitrile-water: A useful alternative to the chichibabin amination
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The title reaction with pyridine, 4-methylpyridine, 3-methylpyridine, 3- bromopyridine, nicotinonitrile, and quinoline yields 2-carboxamido derivatives regioselectively. Isoquinoline is amidated at position 1.
- Kiselyov,Strekowski
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p. 2387 - 2392
(2007/10/02)
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- Method of producing 2-amino-3-nitro-5-halogenopyridine
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A 2-amino-3-nitro-5-halogenopyridine is formed from a 2-acylaminopyridine by way of a 2-acylamino-5-halogenopyridine. The 2-acetamido-5-bromopyridine may be formed from the 2-acylaminopyridine by way of a 2-acylaminopyridinium-HBr3 salt.
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- 1H AND 13C NMR STUDY OF PYRIDYLAMIDES AND THIONAMIDES
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1H and 13C NMR spectra are reported for several pyridylamides and thionamides.Complete analyses of the 13C spectra have yielded the chemical shifts and the direct and long range (13C, 1H) coupling constants. 13C chemical shifts show linear relationship with charge densities computed by CNDO method.The variations in the chemical shifts are discussed.
- Sudha, L. V.,Manogaran, S.,Sathyanarayana, D. N.
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p. 137 - 144
(2007/10/02)
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