1,4-Benzodiazepin-2-Ones in Medicinal Chemistry

• Sternbach LH . 1,4-benzodiazepines. Chemistry and some aspects of the structure–activity relationship.Angew. Chem. Int. Ed. Engl.10, 34–43 (1971).
   PubMed Web of Science ®Google Scholar
• Sternbach LH . Benzodiazepine story.J. Med. Chem.22, 1–7 (1979).
   PubMed Web of Science ®Google Scholar
• Sternbach LH . The benzodiazepine story.J. Psychoactive Drugs15, 15–17 (1983).
   PubMed Web of Science ®Google Scholar
• Hamor TA , Martin,IL, WestGP, EllisGB. The benzodiazepines. In: Progress in Medicinal Chemistry (Volume 20). Elsevier, NY, USA, 157–223 (1983).
   Google Scholar
• Taylor D . Current usage of benzodiazepines in Britain. In: The Benzodiazepines in Current Clinical Practice. Freeman H, Rue Y (Eds). Royal Society of Medicine Services, London, UK, 13–18 (1987).
   Google Scholar
• Harvey SC . Hypnotics and sedatives. In: Goodman Gilman’s The Pharmacological Basis of Therapeutics (7th Edition). Gilman LS, Rall TW, Murad F (Eds). MacMillan, NY, USA, 339–386 (1985).
   Google Scholar
• King MB . Is there still a role for benzodiazepines in general practice?Br. J. Gen. Pract.42, 202–205 (1992).
   PubMedGoogle Scholar
• Ashton CH . The Benzodiazepines: How They Work and How to Withdraw. Churchill Livingstone, Edinburgh, UK (2002).
   Google Scholar
• Reynolds DS . The value of genetic and pharmacological approaches to understanding the complexities of GABAA receptor subtype functions: the anxiolytic effects of benzodiazepines. Pharmacol. Biochem. Behav.90, 37–42 (2008).
   PubMed Web of Science ®Google Scholar
• Zavala F . Benzodiazepines, anxiety and immunity.Pharmacol. Ther.75, 199–216 (1997).
   PubMed Web of Science ®Google Scholar
• James ML , SelleriS, KassiouM. Development of ligands for the peripheral benzodiazepine receptor.Curr. Med. Chem.13, 1991–2001 (2006).
   PubMed Web of Science ®Google Scholar
• Holmes GL . Buccal route for benzodiazepines in treatment of seizures?Lancet353, 608–609 (1999).
   PubMed Web of Science ®Google Scholar
• Curran HV . Benzodiazepines, memory and mood: a review.Psychopharmacology105, 1–8 (1991).
   PubMed Web of Science ®Google Scholar
• Nutt DJ . Overview of diagnosis and drug treatments of anxiety disorders.CNS Spectr.10, 49–56 (2005).
   PubMed Web of Science ®Google Scholar
• Makhlouf MM , AyoubAI, Abdel-FattahMM. Insomnia symptoms and their correlates among the elderly in geriatric homes in Alexandria, Egypt.Sleep Breath.11, 187–194 (2007).
   PubMed Web of Science ®Google Scholar
• Kryger M , MonjanA, BliwiseDet al. Sleep, health, and aging. Bridging the gap between science and clinical practice. Geriatrics 59, 24–26, 29–30 (2004).
   PubMed Web of Science ®Google Scholar
• Stokes TSE , Juarez-GarciaA, Camosso-StefinovicJ, BakerR. Clinical guidelines and evidence review for the epilepsies: diagnosis and management in adults and children in primary and secondary care. Royal College of General Practitioners, London, UK (2004).
   Google Scholar
• Barnard EA , SkolnickP, OlsenRWet al. International Union of Pharmacology. XV. Subtypes of γ-butyric acid A receptors:classification on the basis of subunit structure and receptor function. Pharmacol. Rev. 50(2), 291–313 (1998).
   PubMed Web of Science ®Google Scholar
• Myrick H , AntonRF. Treatment of alcohol withdrawal.Alcohol Health Res. World22(1), 38–43 (1998).
   PubMed Web of Science ®Google Scholar
• Peppers MP . Benzodiazepines for alcohol withdrawal in the elderly and in patients with liver disease.Pharmacotherapy16, 49–57 (1996).
   PubMed Web of Science ®Google Scholar
• McDonald IM . CCK2 receptor antagonists. Expert Opin. Ther. Pat.11(3), 445–462 (2001).
   Web of Science ®Google Scholar
• Evans BE , RittleKE, BockMG, DiPardoRM. Methods for drug discovery: development of potent, selective, orally effective cholescystokinin antagonists.J. Med. Chem.31, 2235–2246 (1988).
   PubMed Web of Science ®Google Scholar
• Bock MG , DiPardoRM, EvansBE, RittleKE. Synthesis and resolution of 3-amino-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-ones. J. Org. Chem.52, 3232–3239 (1987).
   Web of Science ®Google Scholar
• Dourlat J , LiuWQ, GreshN, GarbayC. Novel 1,4-benzodiazepine derivatives with antiproliferative properties on tumor cell lines.Bioorg. Med. Chem. Lett.17, 2527–2530 (2007).
   PubMed Web of Science ®Google Scholar
• Cheng P , ZhangQ, MaYBet al. Synthesis and in vitro anti-hepatitis B virus activities of 4-aryl-6-chloroquinolin-2-one and 5-aryl-7-chloro-1,4-benzodiazepine derivatives. Bioorg. Med. Chem. Lett. 18, 3787–3789 (2008).
   PubMed Web of Science ®Google Scholar
• Boitano A , EmalCD, LeonettiFet al. Structure activity studies of a novel cytotoxic benzodiazepine. Bioorg. Med. Chem. Lett. 13, 3327–3330 (2003).
   PubMed Web of Science ®Google Scholar
• Cleary J , JohnsonKM, OpipariAW, GlickGD. Inhibition of the mitochondrial F1Fo-ATPase by ligands of the peripheral benzodiazepine receptor.Bioorg. Med. Chem. Lett.17, 1667–1670 (2007).
   PubMed Web of Science ®Google Scholar
• Boitano A , EllmanJA, GlickGD, OpipariAW. The proapoptotic benzodiazepine Bz-423 affects the growth and survival of malignant B cells.Cancer Res.63, 6870–6876 (2003).
   PubMed Web of Science ®Google Scholar
• Sundberg TB , NeyGM, SubramanianCet al. The immunomodulatory benzodiazepine Bz-423 inhibits B-cell proliferation by targeting c-Myc protein for rapid and specific degradation. Cancer Res. 66, 1775–1782 (2006).
   PubMed Web of Science ®Google Scholar
• Bhagavathula N , NerusuKC, HanoshA, AslamMN. 7-chloro-5-(4-hydroxyphenyl)-1-methyl-3-(naphthalen-2-ylmethyl)-4,5-dihydro-1H-benzo[b][1,4]diazepin-2(3H)-one (Bz-423), a benzodiazepine, suppresses keratinocyte proliferation and has antipsoriatic activity in the human skin-severe, combined immunodeficient mouse transplant model. J. Pharmacol Exp. Ther.324, 938–947 (2008).
   PubMed Web of Science ®Google Scholar
• Kim K , VolkmanSK, EllmanJA. Synthesis of 3-substituted 1,4-benzodiazepin-2-ones.J. Braz. Chem. Soc.9(4), 375–379 (1998).
   Web of Science ®Google Scholar
• Guandalini L , CellaiC, LaurenzanaAet al. Design, synthesis and preliminary biological evaluation of new hydroxamate histone deacetylase inhibitors as potential antileukemic agents. Bioorg. Med. Chem. Lett. 18, 5071–5074 (2008).
   PubMed Web of Science ®Google Scholar
• Micale N , VairagoundarR, YakovlevAGet al. Design and synthesis of a potent and selective peptidomimetic inhibitor of caspase-3. J. Med. Chem. 47, 6455–6458 (2004).
   PubMedGoogle Scholar
• Micale N , KozikowskiAP, EttariRet al. Novel peptidomimetic cysteine protease inhibitors as potential antimalarial agents. J. Med. Chem.49, 3064–3067 (2006).
   PubMed Web of Science ®Google Scholar
• Ettari R , MicaleN, SchirmeisterTet al. Novel peptidomimetics containing a vinyl ester moiety as highly potent and selective falcipain-2 inhibitors. J. Med. Chem. 52, 2157–2160 (2009)
   PubMedGoogle Scholar
• Horton DA , BourneGT, SmytheML. The combinatorial synthesis of bicyclic privileged structures or privileged substructures.Chem. Rev.103, 893–930 (2003).
   PubMed Web of Science ®Google Scholar
• Burgey CS , StumpCA, NguyenDNet al. Benzodiazepine calcitonin gene-related peptide (CGRP) receptor antagonists: Optimization of the 4-substituted piperidine. Bioorg. Med. Chem. Lett. 16, 5052–5056 (2006).
   PubMed Web of Science ®Google Scholar
• Williams TM , StumpCA, NguyenDNet al. Non-peptide calcitonin gene-related peptide receptor antagonists from a benzodiazepinone lead. Bioorg. Med. Chem. Lett. 16, 2595–2598 (2006).
   PubMed Web of Science ®Google Scholar
• Wood MR , KimJJ, HanWet al. Benzodiazepines as potent and selective bradykinin B1 antagonists. J. Med. Chem. 46, 1803–1806 (2003).
   PubMed Web of Science ®Google Scholar
• Bolli MH , MarfurtJ, GrisostomiCet al. Novel benzo [1,4]diazepin-2-one derivatives as endothelin receptor antagonists. J. Med. Chem. 47, 2776–2795 (2004).
   PubMed Web of Science ®Google Scholar
• Inoue A , YanagisawaM, KimuraSet al. The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proc. Natl Acad. Sci. USA 86, 2863–2867 (1989).
   PubMed Web of Science ®Google Scholar
• Owens AP , NadinA, TalbotACet al. High affinity, bioavailable 3-amino-1,4-benzodiazepin-based γ-secretase inhibitors. Bioorg. Med. Chem. Lett. 13, 4143–4145 (2003).
   PubMed Web of Science ®Google Scholar
• Churcher I , WilliamsS, KerradSet al. Design and synthesis of highly potent benzodiazepine γ-secretase inhibitors: preparation of (2S,3R)-3-(3,4- difluorophenyl)-2-(4-fluorophenyl)-4-hydroxy-N-((3S)-1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]-diazepin-3-yl)butyramide by use of an asymmetric Ireland–Claisen rearrangement. J. Med. Chem. 46, 2275–2278 (2003).
   PubMed Web of Science ®Google Scholar
• Nadin A , LopezJMS, OwensAPet al. New synthesis of 1,3-dihydro-1,4-benzodiazepin-2(2H)-ones and 3-amino-1,3-dihydro-1,4-benzodiazepin-2(2H)-ones: Pd-catalyzed cross-coupling of imidoyl chlorides with organoboronic acids. J. Org. Chem. 68, 2844–2852 (2003).
   PubMed Web of Science ®Google Scholar
• Safaei-Ghomi J , HatamiA. Facile and efficient one-pot protocol for synthesis of 5-phenyl-1,4-benzodiazepin-2-one derivatives.Synth. Comm.38, 297–302 (2008).
   Web of Science ®Google Scholar
• Wu C , BiedigerRJ, KoganTP. A highly practical route to 7-hydroxy-1,3-dihydro-2H-1,4-benzodiazepin-2-one from p-anisidine.Synth. Comm.29, 3509–3516 (1999).
   Web of Science ®Google Scholar
• Laustsen LS , SamsCK. Parallel synthesis of 1,3-dihydro-1,4-benzodiazepin-2-ones employing catch and release.J. Comb. Chem.9, 1094–1103 (2007).
   PubMed Web of Science ®Google Scholar
• Wiklund P , BergmanJ. Ring forming reactions of imines of 2-aminobenzaldehyde and related compounds.Org. Biomol. Chem.1, 367–372 (2003).
   PubMed Web of Science ®Google Scholar
• Dewitt SH , KielyJS, StankovicCJet al. Diversomers – an approach to nonpeptide, nonoligomeric chemical diversity. Proc. Natl Acad. Sci. USA 90, 6909–6913 (1993).
   PubMed Web of Science ®Google Scholar
• Bunin BA , PlunkettMJ, EllmanJA. The combinatorial synthesis and chemical and biological evaluation of a 1,4-benzodiazepine library.Proc. Natl Acad. Sci. USA91, 4708–4712 (1994).
   PubMed Web of Science ®Google Scholar
• Plunkett MJ , EllmanJA. A silicon-based linker for traceless solid-phase synthesis.J. Org. Chem.60, 6006–6007 (1995).
   Web of Science ®Google Scholar
• Plunkett MJ , EllmanJA. Solid-phase synthesis of structurally diverse 1,4-benzodiazepine derivatives using the Stille coupling reaction.J. Am. Chem. Soc.117, 3306–3307 (1995).
   Web of Science ®Google Scholar
• Plunkett MJ , EllmanJA. Germanium and silicon linking strategies for traceless solid-phase synthesis.J. Org. Chem.62, 2885–2893 (1997).
   PubMed Web of Science ®Google Scholar
• Spulak M , LubojackyR, SenelPet al. Direct C-H arylation and alkenylation of 1-substituted tetrazoles: phosphine as stabilizing factor. J. Org. Chem. 75, 241–244 (2010).
   PubMed Web of Science ®Google Scholar
• Lebrasseur N , LarrosaI. Room temperature and phosphine free palladium catalyzed direct C-2 arylation of indoles.J. Am. Chem. Soc.130, 2926–2927 (2008).
   PubMed Web of Science ®Google Scholar
• Li BJ , TianSL, FangZet al. Multiple C-H activations to construct biologically active molecules in a process completely free of organohalogen and organometallic components. Angew. Chem. Int. Ed. 120, 1131–1134 (2008).
   Google Scholar
• Stuart DR , FagnouK. The catalytic cross-coupling of unactivated arenas.Science316, 1172–1175 (2007).
   PubMed Web of Science ®Google Scholar
• Spencer J , ChowdhryBZ, MalletAIet al. C-H activations on a 1H-1,4-benzodiazepin-2(3H)-one template. Tetrahedron 64, 6082–6089 (2008)
   Web of Science ®Google Scholar
• Gribble MW , EllmanJA, BergmanRG. Synthesis of a benzodiazepine-derived rhodium NHC complex by C–H bond activation.Organometallics27, 2152–2155 (2008).
   PubMed Web of Science ®Google Scholar
• Yotphan S , BergmanRG, EllmanJA. Application of Daugulis copper-catalyzed direct arylation to the synthesis of 5-aryl benzotriazepines.Org. Lett.61, 1511–1514 (2009).
   Google Scholar
• McDonald IM , AustinC, BuckIMet al. Novel, achiral 1,3,4-benzotriazepine analogues of 1,4-benzodiazepin-based CCK2 antagonists that display high selectivity over CCK1 receptors. J. Med. Chem. 49(7), 2253–2261 (2006).
   PubMed Web of Science ®Google Scholar
• McDonald IM , BlackJW, BuckIMet al. Optimization of 1,3,4-benzotriazepine-based CCK2 antagonists to obtain potent, orally active inhibitors of gastrin-mediated gastric acid secretion. J. Med. Chem. 50(13), 3101–3112 (2007).
   PubMed Web of Science ®Google Scholar
• Spencer J , GaffenJ, GriffinEet al. Achiral, selective CCK2 receptor antagonists based on a 1,3,5-benzotriazepine-2,4-dione template. Bioorg. Med. Chem. 16, 2974–2983 (2008).
   PubMed Web of Science ®Google Scholar
• McDonald IM , AustinC, BuckIMet al. Discovery and characterization of novel, potent, non-peptide parathyroid hormone-1 receptor antagonists. J. Med. Chem. 50(20), 4789–4792 (2007).
   PubMed Web of Science ®Google Scholar
• Spencer J , SharrattDP, DupontJet al. Synthesis and evaluation of 5-phenyl-1H-1,4-benzodiazepin-2(3H)-one-based palladium complexes as precatalysts in C-C bond forming reactions. Organometallics 24, 5665–5672 (2005).
   Web of Science ®Google Scholar
• Spencer J , RathnamRP, MotukuriMet al. Synthesis of a 1,4-benzodiazepine containing palladacycle with in vitro anticancer and cathepsin B activity. Dalton Trans. 22, 4299–4303 (2009).
   PubMed Web of Science ®Google Scholar
• Spencer J , CasiniA, ZavaOet al. Excellent correlation between cathepsin B inhibition and cytotoxicity for a series of palladacycles. Dalton Trans. 48, 10731–10735 (2009).
   Google Scholar
• Costantino L , BarloccoD. Privileged structures as leads in medicinal chemistry.Curr. Med. Chem.13, 65–85 (2006).
   PubMed Web of Science ®Google Scholar
• Spencer J . Microwave chemistry enabling the synthesis of biologically relevant amines.Future Med. Chem.2(2), 161–168 (2010).
   PubMed Web of Science ®Google Scholar
• Armour DR , AstonN, Morriss et al. 1,4-benzodiazepin-2-one derived neurokinin-1 receptor antagonists. Bioorg. Med. Chem. Lett.7(15), 2037-2042 (1997).
   Web of Science ®Google Scholar

Patents

• University of Michigan: WO061916 (2009).
   Google Scholar
• Merck & Co. Inc: US0148790 (2006).
   Google Scholar
• Merck & Co. Inc: WO099388 (2002).
   Google Scholar
• Actelion Pharmaceuticals Ltd: US124605 (2005).
   Google Scholar
• Merck & Co. Inc: US0024203 (2004).
   Google Scholar
• University of California: US5288514 (1994).
   Google Scholar
• James Black Foundation Ltd: WO0304171 (2003).
   Google Scholar
• James Black Foundation Ltd: US082892 (2004).
   Google Scholar
• James Black Foundation Ltd: WO129120 (2006).
   Google Scholar
• James Black Foundation Ltd: WO135350 (2007).
   Google Scholar