Synthesis and biological evaluation of new 2-(4,5-dihydro-1H-imidazol-2-yl)-3,4-dihydro-2H-1,4-benzoxazine derivatives

Journal of Medicinal Chemistry

Volumn 46, Issue 10, 2003, Pages 1962-1979

  Touzeau, Frédérique ^a   Arrault, Axelle ^a   Guillaumet, Gérald ^a   Scalbert, Elizabeth ^b   Pfeiffer, Bruno ^c   Rettori, Marie Claire ^b   Renard, Pierre ^c   Mérour, Jean Yves ^a  

^a UNIVERSITÉ D'ORLÉANS   (France)

^b INSTITUT DE RECHERCHES INTERNATIONALES SERVIER   (France)

^c ADIR   (France)

Author keywords

[No Author keywords available]

Indexed keywords

2 (4,5 DIHYDRO 1H IMIDAZOL 2 YL) 3,4 DIHYDRO 2H 1,4 BENZOXAZINE; 6 FLUORO 2 (4,5 DIHYDRO 1H IMIDAZOL 2 YL) 4 METHYL 3,4 DIHYDRO 2H 1,4 BENZOXAZINE; ALPHA 1 ADRENERGIC RECEPTOR; ALPHA 2 ADRENERGIC RECEPTOR; BENZOXAZINE DERIVATIVE; IMIDAZOLE DERIVATIVE; IMIDAZOLINE I1 RECEPTOR; IMIDAZOLINE I2 RECEPTOR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CHEMICAL ANALYSIS; CHEMICAL REACTION; CONTROLLED STUDY; DRUG BINDING SITE; DRUG STRUCTURE; DRUG SYNTHESIS; HEART RATE; HYPERTENSION; MALE; MEAN ARTERIAL PRESSURE; NONHUMAN; RAT; SPONTANEOUSLY HYPERTENSIVE RAT;

ADRENAL MEDULLA; ANIMALS; ANTIHYPERTENSIVE AGENTS; BINDING SITES; BLOOD PRESSURE; CATTLE; FRONTAL LOBE; HEART RATE; IMIDAZOLES; KIDNEY; OXAZINES; RABBITS; RADIOLIGAND ASSAY; RATS; RATS, INBRED SHR; RATS, WISTAR; RECEPTORS, ADRENERGIC, ALPHA-1; RECEPTORS, ADRENERGIC, ALPHA-2; RECEPTORS, DRUG; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0037740007     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm021050c     Document Type: Article

References (97)

1. Farsang, C.; Kapocsi, J. Imidazoline Receptors: From Discovery to Antihypertensive Therapy (Facts and Doubts). Brain Res. Bull. 1999, 49, 317-331.
2. Hieble, J. P.; Kolpak, D. C. Mediation of the Hypotensive Action of Systemic Clonidine in the Rat by alpha 2-Adrenoceptors. Br. J. Pharmacol. 1993, 110, 1635-1639.
3. Timmermans, P. B.; Schoop, A. M.; Kwa, H. Y.; Van Zwieten, P. A. Characterization of α-Adrenoceptors Participating in the Central Hypotensive and Sedative Effects of Clonidine using Yohimbine, Rauwolscine and Corynanthine. Eur. J. Pharmacol. 1981, 70, 7-15.
4. 2A-Adrenergic Receptor Subtype. Science 1996, 273, 801-803.
5. 2-Adrenoceptor Transgenic Mice. Br. J. Pharmacol. 1999, 126, 1522-1530.
6. Bousquet, P.; Feldman, J.; Bloch, R.; Schwartz, J. The Nucleus Reticularis Lateralis: A Region Highly Sensitive to Clonidine. Eur. J. Pharmacol. 1981, 69, 389-392.
7. Bousquet, P.; Feldman, J.; Schwartz, J. Central Cardiovascular Effects of α-Adrenergic Drugs: Differences Between Catecholamines and Imidazolines. J. Pharmacol. Exp. Ther. 1984, 230, 232-236.
8. Ernsberger, P.; Giuliano, R.; Willette, R. N.; Reis, D. J. Role of Imidazoline Receptors in the Vasodepressor Response to Clonidine Analogues in the Rostral Ventrolateral Medulla. J. Pharmacol. Exp. Ther. 1990, 253, 408-418.
9. 1-imidazoline Receptors in the Rostral Ventrolateral Medulla. J. Cardiovasc. Pharmacol. 1994, 24, suppl. 1, S1-S8.
10. Feldman, J.; Tibiriça, E.; Bricca, G.; Dontenwill, M.; Belcourt, A.; Bousquet, P. Evidence for the Involvement of Imidazoline Receptors in the Central Hypotensive Effect of Rilmenidine in the Rabbit. Br. J. Pharmacol. 1990, 100, 600-604.
11. Bruban, V.; Feldman, J.; Greney, H.; Dontenwill, M.; Schan, S.; Jarry, C.; Payard, M.; Boutin, J.; Scalbert, E.; Pfeiffer, B.; Renard, P.; Vanhoutte, P.; Bousquet, P. Respective Contributions of Nonadrenergic Mechanisms in the Hypotensive Effect of Imidazoline-like Drugs Br. J. Pharmacol. 2001, 133, 261-266.
12. Bricca, G.; Dontenwill, M.; Molines, A.; Feldman, J.; Belcourt, A.; Bousquet, P. The Imidazoline Preferring Receptor: Binding Studies in Bovine, Rat and Human Brainstem. Eur. J. Pharmacol. 1989, 162, 1-9.
13. Meeley, M. P.; Ernsberger, P.; Granata, A. R.; Reis, D. J. An Endogenous Clonidine-displacing Substance from Bovine Brain: Receptor Binding and Hypotensive Actions in the Ventrolateral Medulla. Life Sci. 1986, 38, 1119-1126.
14. (a) Moldering, G. J. Imidazoline Receptors: Basic Knowledge, Recent Advances and Future Prospects for Therapy and Diagnosis. Drugs Future 1997, 22, 757-772.
15. (b) Bousquet, P.; Bruban, V.; Schann, S.; Feldman, J. Imidazoline Receptors: a Challenge. Pharm. Acta Helv. 2000, 74, 205-209.
16. 1 Imidazoline Receptor: From Binding Site to Therapeutic Target in Cardiovascular Disease. J. Hypertens. 1997, 15 (suppl 1) S9-S23.
17. 2 Imidazoline Binding Sites on Monoamine Oxidases, J. Biol. Chem. 1995, 270, 9856-9861.
18. 2 ligands: A Significant Model Through a Combined Exploration of Structural Diversity and Methodology. J. Med. Chem. 2000, 43, 1109-1122.
19. Li, G.; Regunathan, S.; Barrow, C. J.; Eshragi, J.; Cooper, R.; Reis, D. J. Agmatine: An Endogenous Clonidine-displacing Substance in the Brain. Science 1994, 263, 966-969.
20. Musgrave, I. F.; Badoer, E. Harmane Produces Hypotension Following Microinjection into the RVLM: Possible Role of I(1)-Imidazoline Receptors. Br. J. Pharmacol. 2000, 129, 1057-1059.
21. Raasch, W.; Schäfer, U.; Qadri, F.; Dominiak, P.; Agmatine, an Endogeneous Ligand at Imidazoline Binding Sites does not Antagonize the Clonidine-mediated Blood Pressure Reaction. Br. J. Pharmacol. 2002, 135, 663-672.
22. Chan, S. L. F. Clonidine-displacing Substance and its Putative Role in the Control of Insulin Secretion: A Mini Review. Gen. Pharmacol. 1998, 31, 525-529.
23. Rondu, F.; Le Bihan, G.; Wang, X.; Lamouri, A.; Touboul, E.; Dive, G.; Bellahsene, T.; Pfeiffer, B.; Renard, P.; Guardiola-Lemaitre, B.; Manechez, D.; Penicaud, L.; Ktorza, A.; Godfroid, J. J. Design and Synthesis of Imidazoline Derivatives Active on Glucose Homeostasis in a Rat Model of Type II Diabetes. 1. Synthesis and Biological Activities of N-Benzyl-N′-(arylalkyl)-2-(4′,5′-dihydro-1 ′H-imidazol-2′-yl)piperazines. J. Med. Chem. 1997, 40, 3793-3803.
24. 1A Adrenergic Receptor Agonists: 2′-Heteroaryl and 2′-Oxime Ether Series. Bioorg. Med. Chem. Lett. 2002, 12, 575-579.
25. 1A Subtype Selective 2′-Heteroaryl-2-(phenoxymethyl)imidazolines. Bioorg. Med. Chem. Lett. 2002, 12, 471-475.
26. 2-imidazoline Receptors: Synthesis and Pharmacological Screening. Bioorg. Med. Chem. 2002, 10, 1009-1018.
27. 2-Imidazoline Binding Site Affinity of a Structurally Different Type of Ligands. Bioorg. Med. Chem. 2002, 10, 1525-1523.
28. 2 Receptors. Eur. J. Pharmacol. 1997, 333, 9-15.
29. 2-Adrenoreceptors Profile Modulation and High Antinociceptive Activity of (S)-(-)-2-[1-(Biphenyl-2-yloxy)ethyl]-4,5-dihydro-1H-imidazole. J. Med. Chem. 2002, 45, 32-40.
30. 1D/1B Serotonergic Ligands. Bioorg. Med. Chem. 2001, 9, 613-619.
31. 3 Imidazoline Receptor Antagonist KU14R and Related 2,3-Dihydrobenzo[b]furan Derivatives. Synthesis 2001, 1546-1550.
32. Morgan, N. J.; Chan, S. L. F.; Mourtada, M.; Monks, L. K.; Ramsden, C. A. Imidazolines and Pancreatic Hormone Secretion. Ann. N. Y. Acad. Sci. 1999, 881, 217-228.
33. Pigini, M.; Quaglia, W.; Gentili, F.; Maruci, G.; Cantalamessa, F.; Franchini, S.; Sorbi, C.; Brasili, L. Structure-Activity Relationship at α-Adrenergic Receptors Within a Series of Imidazoline Analogues of Ciralozine. Bioorg. Med. Chem. 2000, 8, 883-888.
34. 2 Selective Ligands. Bioorg. Med. Chem. 2001, 9, 582-592.
35. Saczewski, F.; Debowski, T.; Petrusewicz, J.; Treziak, H.; Krzstaneck E.; Krzstaneck M.; Gdaniec, M.; Nowakowska, E. Synthesis, Structure and Biological Activities of Some N-(4,5-dihydro-1H-imidazol-2-yl)-1,3-dihydrobenzimidazole Derivatives. Arch. Pharm. (Weinheim) 1998, 331, 241-248.
36. Saczewski, F.; Debowski, T.; Gdaniec, M.; Petrusewicz, J.; Turowski, M.; Damasievicz, B. Synthesis, Structure and Anti-aggregatory Effects of Some α-Hydroxy Analogues of 2-Aryliminoimidazolines in Human Platelets. Eur. J. Pharm. Sci. 1996, 4, 85-93.
37. Saczewski, F.; Debowski, T.; Petrusewicz, J.; Gdaniec, M.; Dabrowski, R. K.; Nowakowska, E. Synthesis, Structure and Antiaggregatory Effects of Some N-(4,5-dihydro-1H-imidazol-2-yl)indoles. Il Farmaco 2000, 55, 56-64.
38. 1-PBS-Selective Imidazoline Analogue, trans 1-(4′,5′-Dihydro-1H-imidazol-2′-yl)-methyl-2-hydroxyindane (PMS 952). Bioorg. Med. Chem. 2000, 8, 1861-1869.
39. 1 Imidazoline Receptor Selective Ligand with Hypotensive Activity. J. Med. Chem. 2001, 44, 1588-1593.
40. Pigini, M.; Bousquet, P.; Carotti, A.; Dontenwill, M.; Giannella, M.; Moriconi, R.; Piergentili, A.; Quaglia, W.; Tayebati, S. K.; Brasili, L. Imidazoline Receptors: Qualitative Structure-activity Relationships and Discovery of Tracizoline and Benazoline. Two Ligands with High Affinity and Unprecedented Selectivity. Bioorg. Med. Chem. 1997, 5, 833-841.
41. (a) Chapleo C. B.; Myers P. L. 2-[2-(1,4-Benzodioxanyl)]-2- Imidazoline Hydrochloride. Tetrahedron Lett. 1981, 22, 4839-4842.
42. 2-Adrenoreceptor Antagonists and Potential Antidepressants. J. Med. Chem. 1983, 26, 823-831.
43. 2-site Ligand, 2-(2-Benzofuranyl)-2-imidazoline, in in vivo Noradrenaline Release in Rat Brain Br. J. Pharmacol. 1995, 114, 413P.
44. + Channels in Pancreatic B-cells. Eur. J. Pharmacol. 1994, 264, 81-84.
45. Bartsch, H.; Schwarz, O. Die Polonovski-Reaktion an 3,4-Dihydro-4-methyl-2H-1,4-benzoxazin-2-carbonsäurederivaten; ein Neuer Syntheseweg zu 4H-1,4-Benzoxazinen-10. (Polonovski Reaction of 3,4-Dihydro-4-methyl-2H-1,4-2-carboxylic Acid Derivatives; A New Synthetic Pathway to 4H-1,4-Benzoxazines-10.) J. Heterocycl. Chem. 1982, 19, 1189-1193.
46. 1A Receptor. Bioorg. Med. Chem. Lett. 1997, 7, 763-768.
47. Kotha, S.; Bindra, V.; Kuki, A. Synthesis and Reactions of 3,4-Dihydro-2H-1,4-benzoxazine Derivatives. Heterocycles 1994, 38, 5-8.
48. Lhoste, P.; Massacret, M.; Sinou, D. Asymmetric Synthesis of 2-Vinyl-3,4-dihydro-2H-1,4-benzoxazine Catalysed by Palladium (0) Complexes. Bull. Soc. Chim. Fr. 1997, 134, 343-347.
49. Kajino, M.; Shibouta, Y.; Nishikawa, K.; Meguro, K. Synthesis and Biological Activities of New 2-Substituted 1,4-Benzoxazine Derivatives. Chem. Pharm. Bull. 1991, 39, 2896-2905.
50. Guillaumet, G.; Loubinoux, B.; Coudert, G. Synthesis of Benzoxazines. Tetrahedron Lett. 1978, 26, 2287-2288.
51. Coudert, G.; Guillaumet, G.; Loubinoux, B. A New Synthesis of 3,4-Dihydro-2H-1,4-Benzoxazines using Solid-Liquid Phase-Transfer Catalysis. Synthesis 1979, 541-543.
52. Bartsch, H.; Kropp, W.; Pailer, M. Synthese und Reaktivität von 2- und 3-Hydroxylierten Dihydro-1,4-Benzoxazinen. Monatsch. Chem. 1979, 110, 267-278.
53. Bartsch, H.; Ofner, M.; Schwarz, O.; Thomann, W. 2,3-Dibromo-3,4-dihydro-4H-benzoxazin and their Nucleophilic Displacement Reactions: the First Synthesis of 4-Acetyl-4H-1,4-benzoxazin-3-carbonitrile. Heterocycles 1984, 22, 2789-2797.
54. Kundu, N. G.; Chaudhuri, G.; Upadhyay, A. Palladium- Catalyzed Heteroannulation Leading to Heterocyclic Structures with Two Heteroatoms; A Highly Regio- and Stereoselective Synthesis of (Z)-4-Alkyl-2-alkyl(aryl)idenes-3,4-dihydro-2H-1,4-benzoxazines and (Z)-3-Alkyl(aryl)idenes-4-tosyl-3,4-dihydro-2H-1,4-benzoxazines. J. Org. Chem. 2001, 66, 20-29.
55. Banzatti, C.; Heidempergher, F.; Melloni P. Synthesis of Phenyl-substituted 2H-3,4-Dihydro-3-aminomethyl-1,4-benzoxazines. Intermediates for 1H-2,3,3a,4-Tetrahydroimidazo[5,1-c] [1,4]benzoxazin-1-one Derivatives. Part II. J. Heterocycl. Chem. 1993, 20, 259-265.
56. Combs, D. W.; Rampulla, S. C.; Bell, S. C.; Klaubert, D. H.; Tobia, A. J.; Falotico, R.; Haertlein, B.; Lakas-Weiss, C.; Moor, J. B. 6-Benzoxazinylpyridazin-3-ones: Potent, Long-acting Positive Inotrope and Peripheral Vasodilator Agents. J. Med. Chem. 1990, 33, 380-386.
57. Largeron, M.; Lockhart, B.; Pfeiffer, B.; Fleury, M. B. Synthesis and in Vitro Evaluation of New 8-Amino-1,4-benzoxazine Derivatives as Neuroprotective Antioxidants. J. Med. Chem. 1999, 42, 5043-5052.
58. Bourlot, A.-S.; Sanchez, I.; Dureng, G.; Guillaumet, G.; Massingham, R.; Monteil, A.; Winslow, E.; Pujol, M. D.; Mérour, J. Y. New Substituted 1,4-Benzoxazines Derivatives with Potential Intracellular Calcium Activity. J. Med. Chem. 1998, 41, 3142-3158.
59. Iakovou, K.; Kazanis, M.; Vavayannis, A.; Bruni, G.; Romeo, M. R.; Massarelli, P.; Teramoto, S.; Fujiki, H.; Mori, T. Synthesis of Oxypropanolamine Derivatives of 3,4-Dihydro-2H-1,4-benzoxazine, β-Adrenergic Affinity, Inotropic, Chronotropic and Coronary Vasodilating Activities. Eur. J. Med. Chem. 1999, 34, 903-917.
60. Itoh, K.; Kanzaki, K.; Ikebe, T.; Kuroita, T.; Tomozane, H.; Sonda, S.; Sato, N.; Haga, K.; Kawakita, T. Synthesis and Pharmacological Evaluation of Carboxamides Derivatives as Selective Serotoninergic 5HT4 Receptor Agonists. Eur. J. Med. Chem. 1999, 34, 977-989.
61. Augstein, J.; Monro, A. M.; Hessey, G. W. 2-Guanidinomethyl-2,3-dihydro-4H-benzoxazine sulfate. G.B. Patent 1,057,568, 1967. Chem. Abstr. 1967, 66, 95058z.
62. Carr, J. B. Biologically Active Composition. DE Patent 2811236, 1978. Chem. Abstr. 1978, 89, 197564.
63. Butler, R. C. M.; Chapleo, C. B.; Myers, P. L.; Welbourn, A. P. Synthesis of 2-(2-Imidazolinyl) Substituted 2,3-Dihydro-4H-1,4-benzothiazine and 3,4-Dihydro-2H-1,4-benzoxazines. J. Heterocycl. Chem. 1985, 22, 177-181.
64. Bartsch, H.; Schwarz, O. Zur Synthese von 3,4-Dihydro-2H-1,4-benzoxazin-2- und 3-carbonitrilen. 11. Mitteilung über Studien zur Chemie der 1,4-Oxazine. (Synthesis of 3,4-Dihydro-2H-1,4-benzoxazin-2-and 3-carbonitriles. 11. Chemistry of 1,4-Oxazines). J. Heterocycl. Chem. 1983, 20, 45-48.
65. Masuoka, Y.; Asako, T.; Goto, G.; Noguchi, S. Synthesis of 3,4-Dihydro-2H-1,4-benzoxazine-2-acetates and Related Compounds. Chem. Pharm. Bull. 1986, 34, 130-139.
66. Bartsch, H. Studies on the Chemistry of 1,4-Oxazines, XV [1]: Synthesis of Ethyl 3,4-Dihydro-4-tosyl-2H-1,4-benzoxazine-3-carboxylate. Monatsh Chem. 1987, 118, 273-276.
67. Potter, G. W. H.; Monro, A. M. A Synthetic Entry into 2- und 3-Substituted-Methyl 2,3-Dihydro-1,4-benzoxazine Series. J. Heterocycl. Chem. 1972, 9, 299-301.
68. Bourlot, A. S.; Guillaumet, G.; Mérour, J. Y., A Straightforward Route to 4H-1,4-Benzoxazin-2-Carbaldehydes. J. Heterocycl. Chem. 1996, 31, 191-196.
69. Gryglewska, T.; Gryglewski, R. Synthesis and Basic Pharmacological Properties of N-alkylamides of Benzomorpholine-2-carboxylic acid. Diss. Pharm. Pharmacol. 1969, 21, 25-32. Chem. Abstr. 1969, 71, 61305.
70. Gryglewska, T.; Gryglewski, R. Synthesis and Basic Pharmacological Properties of N-alkylamides of Benzomorpholine-2-carboxylic acid. Diss. Pharm. Pharmacol. 1969, 21, 25-32. Chem. Abstr. 1969, 71, 61305.
71. Chapleo, C. B.; Myers, P. L.; Butler, R. C. M.; Davis, J. A.; Doxey, J. C.; Higgins, S. D.; Myers, M.; Roach, A. G.; Smith, C. F. C.; Stillings, M. R.; Welbourn, A. P. α-Adrenoreceptor Reagents. 2. Effects of Modification of the 1,4-Benzodioxan Ring System on α-Adrenoreceptor Activity. J. Med. Chem. 1984, 27, 570-576.
72. 2-Adrenergic Agonists/Antagonists: The Synthesis and Structure-Activity Relationships of a Series of Indolin-2-yl and Tetrahydroquinolin-2-yl Imidazo-lines. J. Med. Chem. 1987, 30, 1555-1562.
73. 2-Adrenoreceptor Antagonists. J. Med. Chem. 1986, 29, 2000-2003.
74. 2-Adrenoreceptor Antagonists. J. Med. Chem. 1982, 25, 666-670.
75. Hary, U.; Roettig, U.; Paal, M. Efficient Synthesis of 3-(4,5-Dihydro-1H-imidazol-2-yl)-1H-indoles. Tetrahedron Lett. 2001, 42, 5187-5189.
76. Neef, G.; Eder, U.; Sauer, G. One-Step Conversions of Esters to 2-Imidazolines, Benzimidazoles, and Benzothiazoles by Aluminium Organic Reagents. J. Org. Chem. 1981, 46, 2824-2826.
77. Sinhababu, A. K.; Borchardt, R. T. Silica gel-assisted Reduction of Nitrostyrenes to 2-Aryl-1-nitroalkanes wih Sodium Borohydride. Tetrahedron Lett. 1983, 24, 227-230.
78. Bellamy, F. D. Selective Reduction of Aromatic Nitro Compounds with Stannous Chloride in Non Acidic and Non Aqueous Medium. Tetrahedron Lett. 1984, 25, 839-842.
79. Achenbach, H.; Wörth, J. Michigazon, ein neues Phenoxazon aus Streptomyces Michiganensis- Konstitutionsermittlung und Synthese. (Michigazone, a New Phenoxazone Pigment from Streptomices Michiganensis-Structure Determination and Synthesis.) Chem. Ber. 1977, 110, 12-22.
80. Korshin, E. E.; Sabirova, L. I.; Akhmadullin, A. G.; Levin, Y. A. Aminoamidines. 2-[(Arylamino)methyl]imidazolines and their Acylated Derivatives. Izv. Akad. Nauk. Ser. Khim. 1994, 427-429. Chem. Abstr. 1995 123, 143725.
81. Korshin, E. E.; Sabirova, L. I.; Akhmadullin, A. G.; Levin, Y. A. Aminoamidines. 2-[(Arylamino)methyl]imidazolines and their Acylated Derivatives. Izv. Akad. Nauk. Ser. Khim. 1994, 427-429. Chem. Abstr. 1995 123, 143725.
82. Doyle, T. J.; Haseltine, J. Synthesis, Structure, and NMR Characterisation of a Novel [3.3] Metacyclophane. J. Heterocycl. Chem. 1994, 31, 1417-1419.
83. Bergman, J.; Koch, D. Synthesis of Bisindoles from Bisimidazolines. Heterocycl. Commun. 1996, 2, 305-308.
84. Mittchell, R. H.; Lai, Y. H.; Williams, R. V. N-Bromosuccinimide-Dimethylformamide: a Mild, Selective Nuclear Monobromination Reagent for Reactive Aromatic Compounds. J. Org. Chem. 1979, 44, 4733-4735.
85. Arrault, A.; Touzeau, F.; Guillaumet, G.; Mérour, J. Y. A Straightforward Synthesis of 1,2-Dihydronaphtho[2,1-b]furans from 2-Naphthols. Synthesis 1999, 1241-1245.
86. Kozikowski, A. P.; Sugiyama, K.; Springer, J. P. Studies Directed toward the Total Synthesis of the Rubradirin Antibiotics. 2. Synthesis of the Unique Morpholinonaphthoquinone Chromophore: A Lesson in Diels-Alder Regiocontrol by Diene Substituent Selection. J. Org. Chem. 1981, 46, 2426-2428.
87. Besson, T.; Joseph, B.; Moreau, P.; Viaud, M. C.; Coudert, G.; Guillaumet, G. Synthesis and Fluorescent Properties of New Heterobifunctional Fluorescent Probes. Heterocycles 1992, 34, 273-291.
88. Petigara, R. B.; Yale, H. L. Novel Polycyclic Heterocycles VII Synthesis of tetracyclic ketones and Derivatives from Tricyclic 5,11-Dihydrodibenz[b,e][1,4]oxazepines. J. Heterocycl. Chem. 1971, 8, 455-463.
89. Callahan, J. F.; Newslander, K. A.; Burgess, J. L.; Eggleston, D. S.; Nichols, A.; Wong, A.; Huffman, W. F. The Use of γ-Turn Mimetics to Define Peptide Secondary Structure. Tetrahedron 1993, 49, 3479-3488.
90. Plieninger, H.; Sirowej, H.; Rau, D. Uber die alkylierung von Indoxyl-carbonsaure-(2)-estern und uber die Claisen-Umlagerung der Allyloxyindole. (Alkylation of Indoxyl-2-carboxylates and Claisen Rearrangement of (Allyloxy)indoles). Chem. Ber. 1971, 104, 1863-1868.
91. Linstead, R. P.; Weedon, B. C. L.; Wladislaw, B. Anodic Synthesis (XIII). Chain Extension of Fatty Acids with Benzyl Half Esters. J. Chem. Soc. 1955, 1097-1100.
92. Mayer, S.; Arrault, A.; Guillaumet, G.; Mérour, J. Y. Attempted Synthesis of Ethyl 3,4-Dihydro-2H-1,4-benzoxazine-3-carboxylate and 3-acetate. J. Heterocycl. Chem. 2001, 38, 221-225.
93. Gall, W. G.; Astill, B. D.; Boekelheide, V. Synthesis of 7-substituted Indoline Derivatives J. Org. Chem. 1955, 20, 1538-1544.
94. 1 -imidazoline Sites in Bovine Adrenal Medullary Membranes. Naunyn-Schmiedeberg's Arch. Pharmacol. 1993, 348, 70-76.
95. Van Liefde, I.; Vauquelin, G.; De Keyser, J.; Debacker, J. P.; De Vos H. Alpha 2A adrenoceptors and Nonadrenergic Idazoxan Binding Sites in Calf Brain and Retina are Distinct from those in Human Brain. Neurochem. Int. 1993, 22, 501-509.
96. 2 imidazoline Receptors to the cAMP Pathway: Studies with a Hight Selective Ligand Benazoline Mol. Pharmacol. 2000, 57, 1142-1151.
97. Irwin, S. Comprehensive Observational Assessment: A Systematic Quantitative Procedure for Assessing the Behavoral and Physiologic State of the Mouse. Psychopharmacologia 1968, 13, 222-257.