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Current Organic Chemistry


ISSN (Print): 1385-2728
ISSN (Online): 1875-5348

Review Article

Synthesis of Drugs and Biorelevant N-heterocycles Employing Recent Advances in C-N Bond Formation

Author(s): Firdoos Ahmad Sofi and Prasad V. Bharatam*

Volume 24 , Issue 20 , 2020

Page: [2293 - 2340] Pages: 48

DOI: 10.2174/1385272824999200909114144

Price: $65


C-N bond formation is a particularly important step in the generation of many biologically relevant heterocyclic molecules. Several methods have been reported for this purpose over the past few decades. Well-known named reactions like Ullmann-Goldberg coupling, Buchwald-Hartwig coupling and Chan-Lam coupling are associated with the C-N bond formation reactions. Several reviews covering this topic have already been published. However, no comprehensive review covering the synthesis of drugs/ lead compounds using the C-N bond formation reactions was reported. In this review, we cover many modern methods of the C-N bond formation reactions, with special emphasis on metal-free and green chemistry methods. We also report specific strategies adopted for the synthesis of drugs, which involve the C-N bond formation reactions. Examples include anti-cancer, antidepressant, anti-inflammatory, anti-atherosclerotic, anti-histaminic, antibiotics, antibacterial, anti-rheumatic, antiepileptic and anti-diabetic agents. Many recently developed lead compounds generated using the C-N bond formation reactions are also covered in this review. Examples include MAP kinase inhibitors, TRKs inhibitors, Polo-like Kinase inhibitors and MPS1 inhibitors.

Keywords: Biorelevant N-heterocycles, C-N bond formation, Buchwald-Hartwig coupling, drugs, lead molecules, metal free methods, greener approaches.

Graphical Abstract
Ullmann, F. Ueber eine neue Bildungsweise von Diphenylaminderivaten. Ber. Dtsch. Chem. Ges., 1903, 36, 2382-2384.
Goldberg, I. Ueber Phenylirungen bei Gegenwart von Kupfer als Katalysator. Chem. Ber., 1906, 39, 1691-1692.
Hartwig, J.F. Evolution of a fourth generation catalyst for the amination and thioetherification of aryl halides. Acc. Chem. Res., 2008, 41(11), 1534-1544.
[] [PMID: 18681463]
Qiao, J.X.; Lam, P.Y. Recent advances in Chan–Lam coupling reaction: copper‐promoted C–heteroatom bond cross‐coupling reactions with boronic acids and derivatives, 2011.
Chan, D.M.; Monaco, K.L.; Wang, R.P.; Winters, M.P. New N-and O-arylations with phenylboronic acids and cupric acetate. Tetrahedron Lett., 1998, 39, 2933-2936.
Lam, P.Y.; Clark, C.G.; Saubern, S.; Adams, J.; Winters, M.P.; Chan, D.M.; Combs, A. New aryl/heteroaryl C-N bond cross-coupling reactions via arylboronic acid/cupric acetate arylation. Tetrahedron Lett., 1998, 39, 2941-2944.
Cho, S.H.; Kim, J.Y.; Kwak, J.; Chang, S. Recent advances in the transition metal-catalyzed twofold oxidative C-H bond activation strategy for C-C and C-N bond formation. Chem. Soc. Rev., 2011, 40(10), 5068-5083.
[] [PMID: 21643614]
Bariwal, J.; Van der Eycken, E. C-N bond forming cross-coupling reactions: an overview. Chem. Soc. Rev., 2013, 42(24), 9283-9303.
[] [PMID: 24077333]
Zhao, Y.; Xia, W. Recent advances in radical-based C-N bond formation via photo-/electrochemistry. Chem. Soc. Rev., 2018, 47(8), 2591-2608.
[] [PMID: 29619455]
Ruiz-Castillo, P.; Buchwald, S.L. Applications of palladium-catalyzed C-N cross-coupling reactions. Chem. Rev., 2016, 116(19), 12564-12649.
[] [PMID: 27689804]
Magano, J.; Dunetz, J.R. Large-scale applications of transition metal-catalyzed couplings for the synthesis of pharmaceuticals. Chem. Rev., 2011, 111(3), 2177-2250.
[] [PMID: 21391570]
Yin, J. Selected applications of Pd-and Cu-catalyzed carbon-heteroatom cross-coupling reactions in the pharmaceutical industry.Applications of Transition Metal Catalysis in Drug Discovery and Development: An Industrial Perspective; Matthew, L.C.; Barry, M.T., Eds.; John Wiley & Sons Inc., 2012, pp. 97-163.
Surry, D.S.; Buchwald, S.L. Dialkylbiaryl phosphines in Pd-catalyzed amination: a user’s guide. Chem. Sci. (Camb.), 2011, 2(1), 27-50.
[] [PMID: 22432049]
Chan, D.M.T.; Monaco, K.L.; Wang, R-P.; Winters, M.P. New N- and O-arylations with phenylboronic acids and cupric acetate. Tetrahedron Lett., 1998, 39, 2933-2936.
Sharma, R.; Sofi, F.A.; Rana, P.; Bharatam, P.V. Bimetallic Cu–Mn B spinel oxide catalyzed oxidative synthesis of 1,2-disubstituted benzimidazoles from benzyl bromides. New J. Chem., 2019, 43, 4013-4016.
Liang, T.; Tan, Z.; Zhao, H.; Chen, X.; Jiang, H.; Zhang, M. Aerobic copper-catalyzed synthesis of benzimidazoles from diaryl- and alkylamines via tandem triple C–H aminations. ACS Catal., 2018, 8, 2242-2246.
Jia, F.C.; Xu, C.; Zhou, Z.W.; Cai, Q.; Li, D.K.; Wu, A.X. Consecutive cycloaddition/SNAr/reduction/cyclization/oxidation sequences: a copper-catalyzed multicomponent synthesis of fused N-heterocycles. Org. Lett., 2015, 17(11), 2820-2823.
[] [PMID: 25996444]
Tasler, S.; Mies, J.; Lang, M. Applicability aspects of transition metal‐catalyzed aromatic amination protocols in medicinal chemistry. Adv. Synth. Catal., 2007, 349, 2286-2300.
Roughley, S.D.; Jordan, A.M. The medicinal chemist’s toolbox: an analysis of reactions used in the pursuit of drug candidates. J. Med. Chem., 2011, 54(10), 3451-3479.
[] [PMID: 21504168]
Peng, J.; Shang, G.; Chen, C.; Miao, Z.; Li, B. Nucleophilic addition of benzimidazoles to alkynyl bromides/palladium-catalyzed intramolecular C-H vinylation: synthesis of benzo[4,5]imidazo[2,1-a]isoquinolines. J. Org. Chem., 2013, 78(3), 1242-1248.
[] [PMID: 23272698]
Gu, Z.Y.; Zhu, T.H.; Cao, J.J.; Xu, X.P.; Wang, S.Y.; Ji, S.J. Palladium-catalyzed cascade reactions of isocyanides with enaminones: synthesis of 4-aminoquinoline derivatives. ACS Catal., 2013, 4, 49-52.
Chen, M.; Zhang, M.; Xiong, B.; Tan, Z.; Lv, W.; Jiang, H. A novel ruthenium-catalyzed dehydrogenative synthesis of 2-arylquinazolines from 2-aminoaryl methanols and benzonitriles. Org. Lett., 2014, 16(22), 6028-6031.
[] [PMID: 25381883]
Zhang, Z.; Jiang, H.; Huang, Y. Ruthenium-catalyzed redox-neutral C-H activation via N-N cleavage: synthesis of N-substituted indoles. Org. Lett., 2014, 16(22), 5976-5979.
[] [PMID: 25380398]
Bhatt, D.; Patel, N.; Chowdhury, H.; Bharatam, P.V.; Goswami, A. Additive-controlled switchable selectivity from cyanobenzenes to 2-alkynylpyridines: ruthenium(II)-catalyzed [2+2+2] cycloadditions of diynes and alkynylnitriles. Adv. Synth. Catal., 2018, 360, 1876-1882.
Ghosh, K.; Shankar, M.; Rit, R.K.; Dubey, G.; Bharatam, P.V.; Sahoo, A.K. Sulfoximine-assisted one-pot unsymmetrical multiple annulation of arenes: a combined experimental and computational study. J. Org. Chem., 2018, 83(17), 9667-9681.
[] [PMID: 30063342]
Lian, Y.; Hummel, J.R.; Bergman, R.G.; Ellman, J.A. Facile synthesis of unsymmetrical acridines and phenazines by a Rh(III)-catalyzed amination/cyclization/aromatization cascade. J. Am. Chem. Soc., 2013, 135(34), 12548-12551.
[] [PMID: 23957711]
Wang, J.; Zha, S.; Chen, K.; Zhang, F.; Song, C.; Zhu, J. Quinazoline synthesis via Rh(III)-catalyzed intermolecular C-H functionalization of benzimidates with dioxazolones. Org. Lett., 2016, 18(9), 2062-2065.
[] [PMID: 27058735]
Zhu, T.H.; Wang, S.Y.; Tao, Y.Q.; Wei, T.Q.; Ji, S.J. Co(acac)2/O2-mediated oxidative isocyanide insertion with 2-aryl anilines: efficient synthesis of 6-amino phenanthridine derivatives. Org. Lett., 2014, 16(4), 1260-1263.
[] [PMID: 24506323]
Xu, X.; Yang, Y.; Zhang, X.; Yi, W. Direct synthesis of quinolines via Co(III)-catalyzed and DMSO-involved C-H activation/cyclization of anilines with alkynes. Org. Lett., 2018, 20(3), 566-569.
[] [PMID: 29323496]
Wang, H.; Cao, X.; Xiao, F.; Liu, S.; Deng, G.J. Iron-catalyzed one-pot 2,3-diarylquinazolinone formation from 2-nitrobenzamides and alcohols. Org. Lett., 2013, 15(18), 4900-4903.
[] [PMID: 24015845]
Zhao, D.; Zhou, Y.R.; Shen, Q.; Li, J.X. Iron-catalyzed oxidative synthesis of N-heterocycles from primary alcohols. RSC Advances, 2014, 4, 6486-6489.
Suzuki, C.; Hirano, K.; Satoh, T.; Miura, M. Direct synthesis of N-H carbazoles via iridium(III)-catalyzed intramolecular C-H amination. Org. Lett., 2015, 17(6), 1597-1600.
[] [PMID: 25760543]
Tang, Q.; Xia, D.; Jin, X.; Zhang, Q.; Sun, X.Q.; Wang, C. Re/Mg bimetallic tandem catalysis for [4+2] annulation of benzamides and alkynes via C-H/N-H functionalization. J. Am. Chem. Soc., 2013, 135(12), 4628-4631.
[] [PMID: 23469938]
Nair, D.; Scarpello, J.T.; White, L.S.; dos Santos, L.M.F.; Vankelecom, I.F.; Livingston, A.G. Semi-continuous nanofiltration-coupled Heck reactions as a new approach to improve productivity of homogeneous catalysts. Tetrahedron Lett., 2001, 42, 8219-8222.
Patel, N.; Arfeen, M.; Sood, R.; Khullar, S.; Chakraborti, A.K.; Mandal, S.K.; Bharatam, P.V. Can remote N-heterocyclic carbenes coordinate with main group elements? Synthesis, structure, and quantum chemical analysis of N+ -centered complexes. Chemistry, 2018, 24(24), 6418-6425.
[] [PMID: 29504658]
Bharatam, P.V.; Arfeen, M.; Patel, N.; Jain, P.; Bhatia, S.; Chakraborti, A.K.; Khullar, S.; Gupta, V.; Mandal, S.K. Design, synthesis, and structural analysis of divalent N(I) compounds and identification of a new electron-donating ligand. Chemistry, 2016, 22(3), 1088-1096.
[] [PMID: 26615987]
Sofi, F.A.; Sharma, R.; Chakraborti, A.K.; Bharatam, P.V. Metal-free synthesis of 2,3-disubstituted quinazolinones: ionic liquid mediated and iodine-promoted tandem oxidative cyclocondensation of isatoic anhydrides with arylmethyl amines. Eur. J. Org. Chem., 2019, 34, 5887-5893.
Kathuria, D.; Gupta, P.; Chourasiya, S.S.; Sahoo, S.C.; Beifuss, U.; Chakraborti, A.K.; Bharatam, P.V. An unprecedented intramolecular to intermolecular mechanistic switch in 1,1-diaminoazines leading to differential product formation during the I2-induced tandem oxidative transformation. Org. Biomol. Chem., 2019, 17(16), 4129-4138.
[] [PMID: 30969300]
Mohammed, S.; Vishwakarma, R.A.; Bharate, S.B. Iodine catalyzed oxidative synthesis of quinazolin-4(3H)-ones and pyrazolo[4,3-d]pyrimidin-7(6H)-ones via amination of sp3 C-H Bond. J. Org. Chem., 2015, 80(13), 6915-6921.
[] [PMID: 26067767]
Fang, S.; Niu, X.; Yang, B.; Li, Y.; Si, X.; Feng, L.; Ma, C. One-pot synthesis of benzo[4,5]imidazo[1,2-a]quinazoline derivatives via facile transition-metal-free tandem process. ACS Comb. Sci., 2014, 16(7), 328-332.
[] [PMID: 24919956]
Shen, J.; Wang, X.; Lin, X.; Yang, Z.; Cheng, G.; Cui, X. One-Pot regiospecific synthesis of quinoxalines via a CH2-extrusion reaction. Org. Lett., 2016, 18(6), 1378-1381.
[] [PMID: 26925522]
Lu, S.; Gong, Y.; Zhou, D. Transition metal-free oxidative radical decarboxylation/cyclization for the construction of 6-alkyl/aryl phenanthridines. J. Org. Chem., 2015, 80(18), 9336-9341.
[] [PMID: 26302056]
Yadav, S.; Srivastava, M.; Rai, P.; Tripathi, B.P.; Mishra, A.; Singh, J.; Singh, J. Oxidative organophotoredox catalysis: a regioselective synthesis of 2-nitro substituted imidazopyridines and 3-substituted indoles, initiated by visible light. New J. Chem., 2016, 40, 9694-9701.
Chatterjee, T.; Cho, J.Y.; Cho, E.J. Synthesis of substituted oxazoles by visible-light photocatalysis. J. Org. Chem., 2016, 81(16), 6995-7000.
[] [PMID: 27327044]
Chatterjee, T.; Roh, G.B.; Shoaib, M.A.; Suhl, C.H.; Kim, J.S.; Cho, C.G.; Cho, E.J. Visible-light-induced synthesis of carbazoles by in situ formation of photosensitizing intermediate. Org. Lett., 2017, 19(7), 1906-1909.
[] [PMID: 28350473]
Yoo, W.J.; Tsukamoto, T.; Kobayashi, S. Visible light-mediated Ullmann-type C–N coupling reactions of carbazole derivatives and aryl iodides. Org. Lett., 2015, 17(14), 3640-3642.
[] [PMID: 26151428]
Lei, T.; Liu, W-Q.; Li, J.; Huang, M-Y.; Yang, B.; Meng, Q-Y.; Chen, B.; Tung, C-H.; Wu, L-Z. Visible light initiated hantzsch synthesis of 2, 5-diaryl-substituted pyrroles at ambient conditions. Org. Lett., 2016, 18(10), 2479-2482.
[] [PMID: 27199225]
Jiang, H.; Cheng, Y.; Wang, R.; Zhang, Y.; Yu, S. Synthesis of isoquinolines via visible light-promoted insertion of vinyl isocyanides with diaryliodonium salts. Chem. Commun. (Camb.), 2014, 50(46), 6164-6167.
[] [PMID: 24776694]
Parikh, N.; Roy, S.R.; Seth, K.; Kumar, A.; Chakraborti, A.K. ‘On-water’ multicomponent reaction for the diastereoselective synthesis of functionalized tetrahydropyridines and mechanistic insight. Synthesis, 2016, 48, 547-556.
Kommi, D.N.; Kumar, D.; Bansal, R.; Chebolu, R.; Chakraborti, A.K. “All-water” chemistry of tandem N-alkylation–reduction-condensation for synthesis of N-arylmethyl-2-substituted benzimidazoles. Green Chem., 2012, 14, 3329-3335.
Kumar, D.; Seth, K.; Kommi, D.N.; Bhagat, S.; Chakraborti, A.K. Surfactant micelles as microreactors for the synthesis of quinoxalines in water: scope and limitations of surfactant catalysis. RSC Advances, 2013, 3, 15157-15168.
Tanwar, B.; Purohit, P.; Raju, B.N.; Kumar, D.; Kommi, D.N.; Chakraborti, A.K. An “all-water” strategy for regiocontrolled synthesis of 2-aryl quinoxalines. RSC Advances, 2015, 5, 11873-11883.
Sharma, R.; Abdullaha, M.; Bharate, S.B. Metal-free ionic-liquid-mediated synthesis of benzimidazoles and quinazolin-4(3H)-ones from benzylamines. Asian J. Org. Chem., 2017, 6, 1370-1374.
Sahu, P.K.; Sahu, P.K.; Kaurav, M.S.; Messali, M.; Almutairi, S.M.; Sahu, P.L.; Agarwal, D.D. One-pot facile and mild construction of densely functionalized pyrimidines in water via consecutive C–C and C–S bonds formation. RSC Advances, 2018, 8, 33952-33959.
Damon, D.B.; Dugger, R.W.; Hubbs, S.E.; Scott, J.M.; Scott, R.W. Asymmetric synthesis of the cholesteryl ester transfer protein inhibitor torcetrapib. Org. Process Res. Dev., 2006, 10, 472-480.
Guinó, M.; Phua, P.H.; Caille, J.C.; Hii, K.K. A concise asymmetric synthesis of torcetrapib. J. Org. Chem., 2007, 72(16), 6290-6293.
[] [PMID: 17625891]
Caulfield, M.P.; Birdsall, N.J.M. International union of pharmacology. XVII. Classification of muscarinic acetylcholine receptors. Pharmacol. Rev., 1998, 50, 279-290.
[PMID: 9647869]
Abrams, P.; Andersson, K.E.; Buccafusco, J.J.; Chapple, C.; de Groat, W.C.; Fryer, A.D.; Kay, G.; Laties, A.; Nathanson, N.M.; Pasricha, P.J.; Wein, A.J. Muscarinic receptors: their distribution and function in body systems, and the implications for treating overactive bladder. Br. J. Pharmacol., 2006, 148(5), 565-578.
[] [PMID: 16751797]
Prat, M.; Fernández, D.; Buil, M.A.; Crespo, M.I.; Casals, G.; Ferrer, M.; Tort, L.; Castro, J.; Monleón, J.M.; Gavaldà, A.; Miralpeix, M.; Ramos, I.; Doménech, T.; Vilella, D.; Antón, F.; Huerta, J.M.; Espinosa, S.; López, M.; Sentellas, S.; González, M.; Albertí, J.; Segarra, V.; Cárdenas, A.; Beleta, J.; Ryder, H. Discovery of novel quaternary ammonium derivatives of (3R)-quinuclidinol esters as potent and long-acting muscarinic antagonists with potential for minimal systemic exposure after inhaled administration: identification of (3R)-3-[hydroxy(di-2-thienyl)acetyl]oxy-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane bromide (aclidinium bromide). J. Med. Chem., 2009, 52(16), 5076-5092.
[] [PMID: 19653626]
An, D.; Guo, J.H. 2012.
Holst, J.J. The physiology of glucagon-like peptide 1. Physiol. Rev., 2007, 87(4), 1409-1439.
[] [PMID: 17928588]
Kato, N.; Oka, M.; Murase, T.; Yoshida, M.; Sakairi, M.; Yamashita, S.; Yasuda, Y.; Yoshikawa, A.; Hayashi, Y.; Makino, M.; Takeda, M.; Mirensha, Y.; Kakigami, T. Discovery and pharmacological characterization of N-[2-(2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethylamino)-2-methylpropyl]-2 methylpyrazolo[1,5-a]pyrimidine-6-carboxamide hydrochloride (anagliptin hydrochloride salt) as a potent and selective DPP-IV inhibitor. Bioorg. Med. Chem., 2011, 19, 7221-7227.
[] [PMID: 22019046]
Yoshida, T.; Akahoshi, F.; Sakashita, H.; Kitajima, H.; Nakamura, M.; Sonda, S.; Takeuchi, M.; Tanaka, Y.; Ueda, N.; Sekiguchi, S.; Ishige, T.; Shima, K.; Nabeno, M.; Abe, Y.; Anabuki, J.; Soejima, A.; Yoshida, K.; Takashina, Y.; Ishii, S.; Kiuchi, S.; Fukuda, S.; Tsutsumiuchi, R.; Kosaka, K.; Murozono, T.; Nakamaru, Y.; Utsumi, H.; Masutomi, N.; Kishida, H.; Miyaguchi, I.; Hayashi, Y. Discovery and preclinical profile of teneligliptin (3-[(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl]thiazolidine): a highly potent, selective, long-lasting and orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. Bioorg. Med. Chem., 2012, 20(19), 5705-5719.
[] [PMID: 22959556]
McKeage, K. Trelagliptin: first global approval. Drugs, 2015, 75(10), 1161-1164.
[] [PMID: 26115728]
Feng, J.; Gwaltney, S.L.; Stafford, J.A.; Zhang, Z.; Elder, B. J.; Isbester, P.K.; Palmer, G.J.; Salsbury, J.S.; Ulysse, L.; Fornicola, R.S. 2007.
Jain, R.P.; Angelaud, R.; Thompson, A.; Lamberson, C.; Greenfield, S. 2011.
Rektor, I. Perampanel, a novel, non-competitive, selective AMPA receptor antagonist as adjunctive therapy for treatment-resistant partial-onset seizures. Expert Opin. Pharmacother., 2013, 14(2), 225-235.
[] [PMID: 23259931]
aArimoto, I.; Nagato, S.; Sugaya, Y.; Urawa, Y.; Ito, K.; Naka, H.; Omae, T.; Kayano, A.; Nishiura, K. 2007.
bKoyakumaru, K.; Fukunaga, Y. 2009.
Nagasawa, M.; Nishioka, H.; Suzuki, T.; Nagano, E.; Ishii, K.; Nakao, R. 1998.
aSchroeder, J.; Dziewas, G.; Fachinger, T.; Jaeger, B.; Reichel, C.; Renner, S. 2007.
bSoyka, R.; Rall, W.; Schnaubelt, J.; Sieger, P.; Kulinna, C. 2005.
Cooper, M.R.; Chim, H.; Chan, H.; Durand, C. Ceritinib: a new tyrosine kinase inhibitor for non-small-cell lung cancer. Ann. Pharmacother., 2015, 49(1), 107-112.
[] [PMID: 25258420]
Marsilje, T.H.; Pei, W.; Chen, B.; Lu, W.; Uno, T.; Jin, Y.; Jiang, T.; Kim, S.; Li, N.; Warmuth, M.; Sarkisova, Y.; Sun, F.; Steffy, A.; Pferdekamper, A.C.; Li, A.G.; Joseph, S.B.; Kim, Y.; Liu, B.; Tuntland, T.; Cui, X.; Gray, N.S.; Steensma, R.; Wan, Y.; Jiang, J.; Chopiuk, G.; Li, J.; Gordon, W.P.; Richmond, W.; Johnson, K.; Chang, J.; Groessl, T.; He, Y.Q.; Phimister, A.; Aycinena, A.; Lee, C.C.; Bursulaya, B.; Karanewsky, D.S.; Seidel, H.M.; Harris, J.L.; Michellys, P.Y. Synthesis, structure-activity relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine (LDK378) currently in phase 1 and phase 2 clinical trials. J. Med. Chem., 2013, 56(14), 5675-5690.
[] [PMID: 23742252]
Huang, W-S.; Liu, S.; Zou, D.; Thomas, M.; Wang, Y.; Zhou, T.; Romero, J.; Kohlmann, A.; Li, F.; Qi, J.; Cai, L.; Dwight, T.A.; Xu, Y.; Xu, R.; Dodd, R.; Toms, A.; Parillon, L.; Lu, X.; Anjum, R.; Zhang, S.; Wang, F.; Keats, J.; Wardwell, S.D.; Ning, Y.; Xu, Q.; Moran, L.E.; Mohemmad, Q.K.; Jang, H.G.; Clackson, T.; Narasimhan, N.I.; Rivera, V.M.; Zhu, X.; Dalgarno, D.; Shakespeare, W.C. Discovery of Brigatinib (AP26113), a phosphine oxide-containing, potent, orally active inhibitor of anaplastic lymphoma kinase. J. Med. Chem., 2016, 59(10), 4948-4964.
[] [PMID: 27144831]
Li, J.; Zhao, X.; Chen, L.; Guo, H.; Lv, F.; Jia, K.; Yv, K.; Wang, F.; Li, C.; Qian, J.; Zheng, C.; Zuo, Y. Safety and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor YN968D1 in patients with advanced malignancies. BMC Cancer, 2010, 10, 529.
[] [PMID: 20923544]
Yuan, K.H.; Sun, P.Y.; Zhou, Y.S.; Yongjiang, C. 2010.
Esmaeli, B.; Prieto, V.G.; Butler, C.E.; Kim, S.K.; Ahmadi, M.A.; Kantarjian, H.M.; Talpaz, M. Severe periorbital edema secondary to STI571 (Gleevec). Cancer, 2002, 95(4), 881-887.
[] [PMID: 12209733]
Liu, Y.F.; Wang, C.L.; Bai, Y-J.; Han, N.; Jiao, J.P.; Qi, X.L. A facile total synthesis of imatinib base and its analogues. Org. Process Res. Dev., 2008, 12, 490-495.
Breitler, S.; Oldenhuis, N.J.; Fors, B.P.; Buchwald, S.L. Synthesis of unsymmetrical diarylureas via Pd-catalyzed C-N cross-coupling reactions. Org. Lett., 2011, 13(12), 3262-3265.
[] [PMID: 21604792]
Weisberg, E.; Manley, P.; Mestan, J.; Cowan-Jacob, S.; Ray, A.; Griffin, J.D. AMN107 (nilotinib): a novel and selective inhibitor of BCR-ABL. Br. J. Cancer, 2006, 94(12), 1765-1769.
[] [PMID: 16721371]
Moreau, P.; Masszi, T.; Grzasko, N.; Bahlis, N.J.; Hansson, M.; Pour, L.; Sandhu, I.; Ganly, P.; Baker, B.W.; Jackson, S.R.; Stoppa, A.M.; Simpson, D.R.; Gimsing, P.; Palumbo, A.; Garderet, L.; Cavo, M.; Kumar, S.; Touzeau, C.; Buadi, F.K.; Laubach, J.P.; Berg, D.T.; Lin, J.; Di Bacco, A.; Hui, A.M.; van de Velde, H.; Richardson, P.G. Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N. Engl. J. Med., 2016, 374(17), 1621-1634.
[] [PMID: 27119237]
Pickersgill, I.F.; Bishop, J.; Koellner, C.; Gomez, J. M.; Geiser, A.; Hett, R.; Ammoscato, V.; Munk, S.; Lo, Y.; Chui, F.T. 2005.
Beaver, J.A.; Amiri-Kordestani, L.; Charlab, R.; Chen, W.; Palmby, T.; Tilley, A.; Zirkelbach, J.F.; Yu, J.; Liu, Q.; Zhao, L.; Crich, J.; Chen, X.H.; Hughes, M.; Bloomquist, E.; Tang, S.; Sridhara, R.; Kluetz, P.G.; Kim, G.; Ibrahim, A.; Pazdur, R.; Cortazar, P. FDA approval: palbociclib for the treatment of postmenopausal patients with estrogen receptor-positive, HER2-negative metastatic breast cancer. Clin. Cancer Res., 2015, 21(21), 4760-4766.
[] [PMID: 26324739]
Duan, S.; Place, D.; Perfect, H.H.; Ide, N.D.; Maloney, M.; Sutherland, K.; Price Wiglesworth, K.E.; Wang, K.; Olivier, M.; Kong, F.; Leeman, K.; Blunt, J.; Draper, J.; McAuliffe, M.; O’Sullivan, M.; Lynch, D. Palbociclib commercial manufacturing process development. Part I: control of regioselectivity in a Grignard-mediated SNAr cupling. Org. Process Res. Dev., 2016, 20, 1191-1202.
Syed, Y.Y. Ribociclib: first global approval. Drugs, 2017, 77(7), 799-807.
[] [PMID: 28417244]
Chen, L. 2017.
Deeks, E.D. Venetoclax: first global approval. Drugs, 2016, 76(9), 979-987.
[] [PMID: 27260335]
Besbes, S.; Mirshahi, M.; Pocard, M.; Billard, C.; Besbes, S.; Mirshahi, M.; Pocard, M.; Billard, C. New dimension in therapeutic targeting of BCL-2 family proteins. Oncotarget, 2015, 6(15), 12862-12871.
[] [PMID: 25970783]
Hughes, D.L. Patent review of manufacturing routes to oncology drugs: carfilzomib, osimertinib, and venetoclax. Org. Process Res. Dev., 2016, 20, 2028-2042.
Oshiro, Y.; Sato, S.; Kurahashi, N.; Tanaka, T.; Kikuchi, T.; Tottori, K.; Uwahodo, Y.; Nishi, T. Novel antipsychotic agents with dopamine autoreceptor agonist properties: synthesis and pharmacology of 7-[4-(4-phenyl-1-piperazinyl)butoxy]-3,4-dihydro-2(1H)-quinolinone derivatives. J. Med. Chem., 1998, 41(5), 658-667.
[] [PMID: 9513593]
Morita, S.; Kitano, K.; Matsubara, J.; Ohtani, T.; Kawano, Y.; Otsubo, K.; Uchida, M. Practical application of the palladium-catalyzed amination in phenylpiperazine synthesis: an efficient synthesis of a metabolite of the antipsychotic agent aripiprazole. Tetrahedron, 1998, 54, 4811-4818.
Bower, J.F.; Szeto, P.; Gallagher, T. Enantiopure 1,4-benzoxazines via 1,2-cyclic sulfamidates. Synthesis of levofloxacin. Org. Lett., 2007, 9(17), 3283-3286.
[] [PMID: 17661473]
Graul, A.I.; Cruces, E.; Stringer, M. The year’s new drugs & biologics 2015: Part I. Drugs Today (Barc), 2016, 52(1), 41-89.
[] [PMID: 26937494]
Hayashi, K.; Kito, T.; Mitsuyama, J.; Yamakawa, T.; Kuroda, H.; Kawafuchi, H. 2002.
Asaki, T.; Kuwano, K.; Morrison, K.; Gatfield, J.; Hamamoto, T.; Clozel, M. Selexipag: an oral and selective IP prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension. J. Med. Chem., 2015, 58(18), 7128-7137.
[] [PMID: 26291199]
Karmas, G.; Spoerri, P.E. The preparation of hydroxypyrazines and derived chloropyrazines. J. Am. Chem. Soc., 1952, 74, 1580-1584.
Borsini, F.; Evans, K.; Jason, K.; Rohde, F.; Alexander, B.; Pollentier, S. Pharmacology of flibanserin. CNS Drug Rev., 2002, 8(2), 117-142.
[] [PMID: 12177684]
Mohan, R.D.; Krishna, R.P.; Venkat, R.B. 2010.
Garnock-Jones, K.P. Eluxadoline: first global approval. Drugs, 2015, 75(11), 1305-1310.
[] [PMID: 26149369]
Breslin, H.J.; Cai, C.; He, W.; Kavash, R.W. 2005.
Cai, C.; He, W. 2006.
Rasmusson, G.H.; Reynolds, G.F.; Utne, T.; Jobson, R.B.; Primka, R.L.; Berman, C.; Brooks, J.R. Azasteroids as inhibitors of rat prostatic 5 alpha-reductase. J. Med. Chem., 1984, 27(12), 1690-1701.
[] [PMID: 6502599]
Gormley, G.J.; Stoner, E.; Bruskewitz, R.C.; Imperato-McGinley, J.; Walsh, P.C.; McConnell, J.D.; Andriole, G.L.; Geller, J.; Bracken, B.R.; Tenover, J.S. The effect of finasteride in men with benign prostatic hyperplasia. N. Engl. J. Med., 1992, 327(17), 1185-1191.
[] [PMID: 1383816]
Imperato-McGinley, J.; Peterson, R.E.; Gautier, T.; Sturla, E. Androgens and the evolution of male-gender identity among male pseudohermaphrodites with 5α-reductase deficiency. N. Engl. J. Med., 1979, 300(22), 1233-1237.
[] [PMID: 431680]
Batchelor, K.W.; Frye, S.V.; Dorsey, G.F., Jr; Mook, R.A., Jr 1996.
Cainelli, G.; Martelli, G.; Panunzio, M.; Spunta, G.; Nannini, G.; Salle, E.D. 1988.
Satyanarayana, K.; Srinivas, K.; Himabindu, V.; Reddy, G.M. A scaleable synthesis of dutasteride: A selective 5α-reductase inhibitor. Org. Process Res. Dev., 2007, 11, 842-845.
Ohtsu, Y.; Susaki, Y.; Noguchi, K. Absorption, distribution, metabolism, and excretion of the novel helicase-primase inhibitor, amenamevir (ASP2151), in rodents. Eur. J. Drug Metab. Pharmacokinet., 2018, 43(6), 693-706.
[] [PMID: 29748821]
Kontani, T.; Miyata, J.; Hamaguchi, W.; Kawano, T.; Kamikawa, A.; Suzuki, H.; Sudo, K. 2005.
Watson, L. 2017.
Nyirjesy, P.; Schwebke, J.R. Secnidazole: next-generation antimicrobial agent for bacterial vaginosis treatment. Future Microbiol., 2018, 13, 507-524.
[] [PMID: 29327947]
Zeng, Y.F.; Yi, Z.H. 2014.
Yee, M.K.; Nafee, T.; Daaboul, Y.; Korjian, S.; AlKhalfan, F.; Kerneis, M.; Wiest, C.; Goldhaber, S.Z.; Hernandez, A.F.; Hull, R.D.; Cohen, A.T.; Harrington, R.A.; Gibson, C.M. Increased benefit of betrixaban among patients with a history of venous thromboembolism: a post-hoc analysis of the APEX trial. J. Thromb. Thrombolysis, 2018, 45(1), 1-8.
[] [PMID: 29188425]
Pandey, A.; Leitao, E.P.T.; Rato, J.; Song, Z.J. 2011.
Scott, L.J. Niraparib: first global approval. Drugs, 2017, 77(9), 1029-1034.
[] [PMID: 28474297]
Wallace, D.J.; Baxter, C.A.; Brands, K.J.M.; Bremeyer, N.; Brewer, S.E.; Desmond, R.; Emerson, K.M.; Foley, J.; Fernandez, P.; Hu, W.; Keen, S.P.; Mullens, P.; Muzzio, D.; Sajonz, P.; Tan, L.; Wilson, R.D.; Zhou, G.; Zhou, G. Development of a fit-for-purpose large-scale synthesis of an oral parp inhibitor. Org. Process Res. Dev., 2011, 15, 831-840.
Hughes, D.L. Patent review of manufacturing routes to recently approved parp inhibitors: Olaparib, rucaparib, and niraparib. Org. Process Res. Dev., 2017, 21, 1227-1244.
Charrier, J.D.; Miller, A.; Kay, D.P.; Brenchley, G.; Twin, H.C.; Collier, P.N.; Ramaya, S.; Keily, S.B.; Durrant, S.J.; Knegtel, R.M.A.; Tanner, A.J.; Brown, K.; Curnock, A.P.; Jimenez, J.M. Discovery and structure-activity relationship of 3-aminopyrid-2-ones as potent and selective interleukin-2 inducible T-cell kinase (Itk) inhibitors. J. Med. Chem., 2011, 54(7), 2341-2350.
[] [PMID: 21391610]
Dyrager, C.; Möllers, L.N.; Kjäll, L.K.; Alao, J.P.; Dinér, P.; Wallner, F.K.; Sunnerhagen, P.; Grøtli, M. Design, synthesis, and biological evaluation of chromone-based p38 MAP kinase inhibitors. J. Med. Chem., 2011, 54(20), 7427-7431.
[] [PMID: 21905739]
Albaugh, P.; Fan, Y.; Mi, Y.; Sun, F.; Adrian, F.; Li, N.; Jia, Y.; Sarkisova, Y.; Kreusch, A.; Hood, T.; Lu, M.; Liu, G.; Huang, S.; Liu, Z.; Loren, J.; Tuntland, T.; Karanewsky, D.S.; Seidel, H.M.; Molteni, V.S.; Seidel, H.M.; Molteni, V. Discovery of GNF-5837, a selective TRK inhibitor with efficacy in rodent cancer tumor models. ACS Med. Chem. Lett., 2012, 3(2), 140-145.
[] [PMID: 24900443]
Beria, I.; Ballinari, D.; Bertrand, J.A.; Borghi, D.; Bossi, R.T.; Brasca, M.G.; Cappella, P.; Caruso, M.; Ceccarelli, W.; Ciavolella, A.; Cristiani, C.; Croci, V.; De Ponti, A.; Fachin, G.; Ferguson, R.D.; Lansen, J.; Moll, J.K.; Pesenti, E.; Posteri, H.; Perego, R.; Rocchetti, M.; Storici, P.; Volpi, D.; Valsasina, B. Identification of 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives as a new class of orally and selective Polo-like kinase 1 inhibitors. J. Med. Chem., 2010, 53(9), 3532-3551.
[] [PMID: 20397705]
Duffey, M.O.; Vos, T.J.; Adams, R.; Alley, J.; Anthony, J.; Barrett, C.; Bharathan, I.; Bowman, D.; Bump, N.J.; Chau, R.; Cullis, C.; Driscoll, D.L.; Elder, A.; Forsyth, N.; Frazer, J.; Guo, J.; Guo, L.; Hyer, M.L.; Janowick, D.; Kulkarni, B.; Lai, S.J.; Lasky, K.; Li, G.; Li, J.; Liao, D.; Little, J.; Peng, B.; Qian, M.G.; Reynolds, D.J.; Rezaei, M.; Scott, M.P.; Sells, T.B.; Shinde, V.; Shi, Q.J.; Sintchak, M.D.; Soucy, F.; Sprott, K.T.; Stroud, S.G.; Nestor, M.; Visiers, I.; Weatherhead, G.; Ye, Y.; D’Amore, N. Discovery of a potent and orally bioavailable benzolactam-derived inhibitor of Polo-like kinase 1 (MLN0905). J. Med. Chem., 2012, 55(1), 197-208.
[] [PMID: 22070629]
Bindi, S.; Fancelli, D.; Alli, C.; Berta, D.; Bertrand, J.A.; Cameron, A.D.; Cappella, P.; Carpinelli, P.; Cervi, G.; Croci, V.; D’Anello, M.; Forte, B.; Giorgini, M.L.; Marsiglio, A.; Moll, J.; Pesenti, E.; Pittalà, V.; Pulici, M.; Riccardi-Sirtori, F.; Roletto, F.; Soncini, C.; Storici, P.; Varasi, M.; Volpi, D.; Zugnoni, P.; Vianello, P. Thieno[3,2-c]pyrazoles: a novel class of Aurora inhibitors with favorable antitumor activity. Bioorg. Med. Chem., 2010, 18(19), 7113-7120.
[] [PMID: 20817473]
Caldarelli, M.; Angiolini, M.; Disingrini, T.; Donati, D.; Guanci, M.; Nuvoloni, S.; Posteri, H.; Quartieri, F.; Silvagni, M.; Colombo, R. Synthesis and SAR of new pyrazolo[4,3-h]quinazoline-3-carboxamide derivatives as potent and selective MPS1 kinase inhibitors. Bioorg. Med. Chem. Lett., 2011, 21(15), 4507-4511.
[] [PMID: 21723120]
Kusakabe, K.; Ide, N.; Daigo, Y.; Itoh, T.; Higashino, K.; Okano, Y.; Tadano, G.; Tachibana, Y.; Sato, Y.; Inoue, M.; Wada, T.; Iguchi, M.; Kanazawa, T.; Ishioka, Y.; Dohi, K.; Tagashira, S.; Kido, Y.; Sakamoto, S.; Yasuo, K.; Maeda, M.; Yamamoto, T.; Higaki, M.; Endoh, T.; Ueda, K.; Shiota, T.; Murai, H.; Nakamura, Y. Diaminopyridine-based potent and selective mps1 kinase inhibitors binding to an unusual flipped-Peptide conformation. ACS Med. Chem. Lett., 2012, 3(7), 560-564.
[] [PMID: 24900510]
Dao, P.; Jarray, R.; Le Coq, J.; Lietha, D.; Loukaci, A.; Lepelletier, Y.; Hadj-Slimane, R.; Garbay, C.; Raynaud, F.; Chen, H. Synthesis of novel diarylamino-1,3,5-triazine derivatives as FAK inhibitors with anti-angiogenic activity. Bioorg. Med. Chem. Lett., 2013, 23(16), 4552-4556.
[] [PMID: 23845217]
Guo, S.; Song, Y.; Huang, Q.; Yuan, H.; Wan, B.; Wang, Y.; He, R.; Beconi, M.G.; Franzblau, S.G.; Kozikowski, A.P. Identification, synthesis, and pharmacological evaluation of tetrahydroindazole based ligands as novel antituberculosis agents. J. Med. Chem., 2010, 53(2), 649-659.
[] [PMID: 20000470]
Han, K.; Li, Y.; Zhang, Y.; Teng, Y.; Ma, Y.; Wang, M.; Wang, R.; Xu, W.; Yao, Q.; Zhang, Y.; Qin, H.; Sun, H.; Yu, P. Design, synthesis and docking study of novel tetracyclic oxindole derivatives as α-glucosidase inhibitors. Bioorg. Med. Chem. Lett., 2015, 25(7), 1471-1475.
[] [PMID: 25759031]
Johns, B.A.; Weatherhead, J.G.; Allen, S.H.; Thompson, J.B.; Garvey, E.P.; Foster, S.A.; Jeffrey, J.L.; Miller, W.H. 1,3,4-Oxadiazole substituted naphthyridines as HIV-1 integrase inhibitors. Part 2: SAR of the C5 position. Bioorg. Med. Chem. Lett., 2009, 19(6), 1807-1810.
[] [PMID: 19217284]
Schlapbach, A.; Heng, R.; Di Padova, F. A novel Pd-catalyzed cyclization reaction of ureas for the synthesis of dihydroquinazolinone p38 kinase inhibitors. Bioorg. Med. Chem. Lett., 2004, 14(2), 357-360.
[] [PMID: 14698158]
Oza, V.B.; Smith, C.; Raman, P.; Koepf, E.K.; Lashuel, H.A.; Petrassi, H.M.; Chiang, K.P.; Powers, E.T.; Sachettinni, J.; Kelly, J.W. Synthesis, structure, and activity of diclofenac analogues as transthyretin amyloid fibril formation inhibitors. J. Med. Chem., 2002, 45(2), 321-332.
[] [PMID: 11784137]
Pretolani, M.; Ruffié, C.; Lapa e Silva, J.R.; Joseph, D.; Lobb, R.R.; Vargaftig, B.B. Antibody to very late activation antigen 4 prevents antigen-induced bronchial hyperreactivity and cellular infiltration in the guinea pig airways. J. Exp. Med., 1994, 180(3), 795-805.
[] [PMID: 7914907]
Keszthelyi, E.; Karlik, S.; Hyduk, S.; Rice, G.P.A.; Gordon, G.; Yednock, T.; Horner, H. Evidence for a prolonged role of alpha 4 integrin throughout active experimental allergic encephalomyelitis. Neurology, 1996, 47(4), 1053-1059.
[] [PMID: 8857744]
Ianaro, A.; Cicala, C.; Calignano, A.; Koteliansky, V.; Gotwals, P.; Bucci, M.; Gerli, R.; Santucci, L.; Fiorucci, S.; Cirino, G. Anti-very late antigen-1 monoclonal antibody modulates the development of secondary lesion and T-cell response in experimental arthritis. Lab. Invest., 2000, 80(1), 73-80.
[] [PMID: 10653005]
Tilley, J.W. VLA-4 antagonists. Expert Opin. Ther. Pat., 2002, 12, 991-1008.
Podolsky, D.K.; Lobb, R.; King, N.; Benjamin, C.D.; Pepinsky, B.; Sehgal, P.; deBeaumont, M. Attenuation of colitis in the cotton-top tamarin by anti-alpha 4 integrin monoclonal antibody. J. Clin. Invest., 1993, 92(1), 372-380.
[] [PMID: 7686922]
Saku, O.; Ohta, K.; Arai, E.; Nomoto, Y.; Miura, H.; Nakamura, H.; Fuse, E.; Nakasato, Y. Synthetic study of VLA-4/VCAM-1 inhibitors: synthesis and structure-activity relationship of piperazinylphenylalanine derivatives. Bioorg. Med. Chem. Lett., 2008, 18(3), 1053-1057.
[] [PMID: 18160288]
Wolfe, J.P.; Singer, R.A.; Yang, B.H.; Buchwald, S.L. Highly active palladium catalysts for Suzuki coupling reactions. J. Am. Chem. Soc., 1999, 121, 9550-9561.
Lassoie, M-A.; Broeders, F.; Collart, P.; Defrère, L.; de Laveleye-Defais, F.; Demaude, T.; Gassama, A.; Guillaumet, G.; Hayez, J-C.; Kiss, L.; Knerr, L.; Nicolas, J-M.; Norsikian, S.; Quéré, L.; Routier, S.; Verbois, V.; Provins, L. 2,6-Quinolinyl derivatives as potent VLA-4 antagonists. Bioorg. Med. Chem. Lett., 2007, 17(1), 142-146.
[] [PMID: 17035017]
Shinozuka, T.; Shimada, K.; Matsui, S.; Yamane, T.; Ama, M.; Fukuda, T.; Taki, M.; Takeda, Y.; Otsuka, E.; Yamato, M.; Naito, S. Arylamine based cathepsin K inhibitors: investigating P3 heterocyclic substituents. Bioorg. Med. Chem., 2006, 14(20), 6807-6819.
[] [PMID: 16829073]
Gudmundsson, K.S.; Johns, B.A.; Allen, S.H. Pyrazolopyridines with potent activity against herpesviruses: effects of C5 substituents on antiviral activity. Bioorg. Med. Chem. Lett., 2008, 18(3), 1157-1161.
[] [PMID: 18086523]
Yeh, V.S.C.; Patel, J.R.; Yong, H.; Kurukulasuriya, R.; Fung, S.; Monzon, K.; Chiou, W.; Wang, J.; Stolarik, D.; Imade, H.; Beno, D.; Brune, M.; Jacobson, P.; Sham, H.; Link, J.T. Synthesis and biological evaluation of heterocycle containing adamantane 11β-HSD1 inhibitors. Bioorg. Med. Chem. Lett., 2006, 16(20), 5414-5419.
[] [PMID: 16899366]
Andrés, J.I.; Alcázar, J.; Alonso, J.M.; De Lucas, A.I.; Iturrino, L.; Biesmans, I.; Megens, A.A. Synthesis of 7-amino-3a,4-dihydro-3H-[1]benzopyrano[4,3-c]isoxazole derivatives displaying combined α2-adrenoceptor antagonistic and 5-HT reuptake inhibiting activities. Bioorg. Med. Chem., 2006, 14(13), 4361-4372.
[] [PMID: 16540335]

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