Oxytocin receptor ligands: A survey of the patent literature

Expert Opinion on Therapeutic Patents

Volumn 18, Issue 11, 2008, Pages 1239-1251

  Gimpl, Gerald ^a  

^a JOHANNES GUTENBERG UNIVERSITY   (Germany)

Author keywords

Autism; Lactation; Oxytocin; Oxytocin antagonist; Parturition; Preterm labor

Indexed keywords

1 [1 [4 [1 (2 METHYL 1 OXIDOPYRIDIN 3 YLMETHYL)PIPERIDIN 4 YLOXYL] 2 METHOXYBENZOYL]PIPERIDIN 4 YL] 1,4 DIHYDROBENZ[D][1,3]OXAZIN 2 ONE; 1 [[7,7 DIMETHYL 2,2 AMINO 4 (METHYLSULFONYL)BUTYRAMIDO)BICYCLO[2.2.1] HEPTAN 1 YL] METHYL]SULFONYL 4 (2 METHYLPHENYL)PIPERAZINE; 3 INDAN 2 YL 1 [1 (2 METHYL 1,3, OXAZOL 4 YL) 2 MORPHOLIN 4 YL 2 OXOETHYL] 6 (1 METHYLPROPYL) 2,5 PIPERAZINEDIONE; 4 CHLORO 3 [5 CHLORO 1 (2,4 DIMETHOXYBENZYL) 3 METHYL 2 OXO 2,3 DIHYDRO 1H INDOL 3 YL] N ETHYL N (3 PYRIDYLMETHYL) BENZAMIDE; ARGIPRESSIN; ATOSIBAN; BARUSIBAN; CARBETOCIN; DIAZEPINE DERIVATIVE; DURATOCIN; FE 220440; GSK 221149A; L 368 899; L 372 662; LIGAND; LY 371257; OXYTOCIN; OXYTOCIN ANTAGONIST; OXYTOCIN DERIVATIVE; OXYTOCIN RECEPTOR; PROTEIN INHIBITOR; PYRROLIDINE DERIVATIVE; SSR 126768A; TT 235; UNCLASSIFIED DRUG; VASOPRESSIN DERIVATIVE; VASOPRESSIN RECEPTOR;

ABSENCE OF SIDE EFFECTS; ANTIINFLAMMATORY ACTIVITY; AUTISM; DRUG ABSORPTION; DRUG HALF LIFE; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG STRUCTURE; GROWTH INHIBITION; HUMAN; INFLAMMATION; LABOR INDUCTION; LABOR INHIBITION; LIGAND BINDING; NONHUMAN; OSTEOPOROSIS; PATENT; PREMATURE LABOR; PSYCHOPATHY; RECEPTOR AFFINITY; REVIEW; UNSPECIFIED SIDE EFFECT;

EID: 56849092322     PISSN: 13543776     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543776.18.11.1239     Document Type: Review

References (112)

1. Gimpl G, Fahrenholz F. The oxytocin receptor system: structure, function, and regulation. Physiol Rev 2001;81:629-83
2. Nishimori K, Young LJ, Guo Q, et al. Oxytocin is required for nursing but is not essential for parturition or reproductive behavior. Proc Natl Acad Sci USA 1996;93:11699-704
3. Takayanagi Y, Yoshida M, Bielsky IF, et al. Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice. Proc Natl Acad Sci USA 2005;102:16096-101
4. Gorbulev V, Buchner H, Akhundova A, et al. Molecular cloning and functional characterization of V2 [8-lysine] vasopressin and oxyrocin receptors from a pig kidney cell line. Eur J Biochem 1993;215:1-7
5. Akerlund M, Bossmar T, Brouard R, et al. Receptor binding of oxytocin and vasopressin antagonists and inhibitory effects on isolated myometrium from preterm and term pregnant women. Br J Obstet Gynaecol 1999;106:1047-53
6. Ku CY, Qian A, Wen Y, et al. Oxytocin stimulates myometrial guanosine triphosphatase and phospholipase-C activities via coupling to G alpha q/ 11. Endocrinology 1995;136:1509-15
7. Strakova Z, Soloff MS. Coupling of oxytocin receptor to G proteins in rat myometrium during labor: gi receptor interaction. Am J Physiol 1997;272:E870-6
8. Zingg HH, Laporte SA. The oxytocin receptor. Trends Endocrinol Metab 2003;14:222-7
9. Fuchs AR, Fuchs F, Husslein P, et al. Oxytocin receptors and human parturition: a dual role for oxytocin in the initiation of labor. Science 1982;215:1396-8
10. Blanks AM, Shmygol A, Thornton S. Regulation of oxytocin receptors and oxytocin receptor signaling. Semin Reprod Med 2007;25:52-9
11. Smith MP, Ayad VJ, Mundell SJ, et al. Internalization and desensitization of the oxytocin receptor is inhibited by Dynamin and clathrin mutants in human embryonic kidney 293 cells. Mol Endocrinol 2006;20:379-88
12. Devost D, Zingg HH. Identification of dimeric and oligomeric complexes of the human oxytocin receptor by co-immunoprecipitation and bioluminescence resonance energy transfer. J Mol Endocrinol 2003;31:461-71
13. Terrillon S, Durroux T, Mouillac B, et al. Oxytocin and Vasopressin V1a and V2 Receptors Form Constitutive Homo- and Heterodimers during Biosynthesis. Mol Endocrinol 2003; 17:677-91
14. Chini B, Manning M. Agonist selectivity in the oxytocin/vasopressin receptor family: new insights and challenges. Biochem Soc Trans 2007;35:737-41
15. Hawtin SR, Ha SN, Pettibone DJ, et al. A Gly/Ala switch contributes to high affinity binding of benzoxazinone-based non-peptide oxytocin receptor antagonists. FEBS Lett 2005;579:349-56
16. Chini B, Manning M, Guillon G. Affinity and efficacy of selective agonists and antagonists for vasopressin and oxytocin receptors: an "easy guide" to receptor pharmacology. Prog Brain Res 2008; 170:513-7
17. Manning M, Stoev S, Chini B, et al. Peptide and non-peptide agonists and antagonists for the vasopressin and oxytocin V(1a), V(1b), V2; and OT receptors: research tools and potential therapeutic agents. Prog Brain Res 2008;170:473-512
18. Manning M, Cheng LL, Klis WA, et al. Advances in the design of selective antagonists, potential tocolytics, and radioiodinated ligands for oxytocin receptors. Adv Exp Med Biol 1995;395:559-83
19. Manning M, Sawyer WH. 4-Threonine-oxytocin: a more active and specific oxytocic agent than oxytocin. Nature 1970;227:715-6
20. Elands J, Barberis C, Jard S, et al. 125I-labelled d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH29;] OVT: a selective oxytocin receptor ligand. Eur J Pharmacol 1988;147:197-207
21. Melin P, Trojnar J, Johansson B, et al. Synthetic antagonists of the myometrial response to vasopressin and oxytocin. J Endocrinol 1986;111:125-31
22. Reversi A, Rimoldi V, Marrocco T, et al. The oxytocin receptor antagonist atosiban inhibits cell growth via a "biased agonist" mechanism. J Biol Chem 2005;280:16311-8
23. Nilsson L, Reinheimer T, Steinwall M, et al. FE 200 440: a selective oxytocin antagonist on the term-pregnant human uterus. BJOG 2003;110:1025-8
24. Pierzynski P, Lemancewicz A, Reinheimer T, et al. Inhibitory effect of barusiban and atosiban on oxytocin-induced contractions of myometrium from preterm and term pregangt women. J Soc Gynecol Investig 2004; 11
25. Gimpl G, Postina R, Fahrenholz F, et al. Binding domains of the oxytocin receptor for the selective oxytocin receptor antagonist barusiban in comparison to the agonists oxytocin and carbetocin. Eur J Pharmacol 2005;510:9-16
26. Flouret G, Wilson L. Oxytocin antagonist. US19945373089; 1994
27. Pak SC, Bertoncini D, Meyer W, et al. Comparison of binding affinity of oxytocin antagonists to human and rat uterine oxytocin receptors and their correlation to the rat uterine oxytocic bioassay. Biol Reprod 1994;51:1140-4
28. Williams PD, Bock MG, Evans BE, et al. Progress in the development of oxytocin antagonists for use in preterm labor. Adv Exp Med Biol 1998;449:473-9
29. Manning M, Miteva K, Pancheva S, et al. Design and synthesis of highly selective in vitro and in vivo uterine receptor antagonists of oxytocin: comparisons with Atosiban. Int J Pept Protein Res 1995;46:244-52
30. Terrillon S, Cheng LL, Stoev S, et al. Synthesis and characterization of fluorescent antagonists and agonists for human oxytocin and vasopressin V1;(a) receptors. J Med Chem 2002;45:2579-88
31. Albizu L, Teppaz G, Seyer R, et al. Toward efficient drug screening by homogeneous assays based on the development of new fluorescent vasopressin and oxytocin receptor ligands. J Med Chem 2007;50:4976-85
32. Chini B, Chinol M, Cassoni P, et al. Improved radiotracing of oxytocin receptor-expressing tumours using the new [111;In]-DOTA-Lys8;-deamino-vasotocin analogue. Br J Cancer 2003;89:930-6
33. Bussolati G, Cassoni P, Chini B. Cytotoxic or radioactive conjugates able to bind to oxytocin receptors. WO2002098447; 2002
34. Barth T, Jost K, Rychlik I. Milk-ejecting and uterotonic activities of oxytocin analogues in rats. Endocrinol Exp 1975;9:35-42
35. Atke A, Vilhardt H. Uretotonic activity and myometrial receptor affinity of 1-deamino-1-carba-2-tyrosine(O-methyl)-oxytocin. Acta Endocrinol Copenh 1987;115:155-60
36. Engstrom T, Barth T, Melin P, et al. Oxytocin receptor binding and uterotonic activity of carbetocin and its metabolites following enzymatic degradation. Eur J Pharmacol 1998;355:203-10
37. Stymiest JL, Mitchell BF, Wong S, et al. Synthesis of oxytocin analogues with replacement of sulfur by carbon gives potent antagonists with increased stability. J Org Chem 2005;70:7799-809
38. Hawtin SR, Howard HC, Wheatley M. Identification of an extracellular segment of the oxytocin receptor providing agonist-specific binding epitopes. Biochem J 2001;354:465-72
39. Wesley VJ, Hawtin SR, Howard HC, et al. Agonist-specific, high-affinity binding epitopes are contributed by an arginine in the N-terminus of the human oxytocin receptor. Biochemistry 2002;41:5086-92
40. Evans BE, Lundell GF, Gilbert KF, et al. Nanomolar-affinity, non-peptide oxytocin receptor antagonists. J Med Chem 1993;36:3993-4005
41. Pettibone DJ, Guidotti M, Harrell CM, et al. Progress in the development of oxytocin antagonists for use in preterm labor. Adv Exp Med Biol 1995;395:601-12
42. Yamamura Y, Ogawa H, Chihara T, et al. OPC-21268, an orally effective, nonpeptide vasopressin V1 receptor antagonist. Science 1991;252:572-4
43. Evans BE, Leighton JL, Rittle KE, et al. Orally active, nonpeptide oxytocin antagonists. J Med Chem 1992;35:3919-27
44. Merck & Co. Tocolytic oxytocin receptor antagonists. WO1996022775; 1996
45. Merck & Co. Benzoxazinone and benzopyrimidinone piperidinyl tocolytic oxytocin receptor antagonists. US19975756497; 1997
46. Liddle J, Allen MJ, Borthwick AD, et al. The discovery of GSK221149A: a potent and selective oxytocin antagonist. Bioorg Med Chem Lett 2008;18:90-4
47. McCafferty GP, Pullen MA, Wu C, et al. Use of a novel and highly selective oxytocin receptor antagonist to characterize uterine contractions in the rat. Am J Physiol Regul Integr Comp Physiol 2007;293:R299-305
48. Ferring BV. Piperazines as oxtocin agonists. WO2005023812; 2005
49. Ferring BV. Benzamide derivatives as oxytocin agonists and vasopressin antagonists. WO2004072083; 2004
50. Serradeil-Le GC, Valette G, Foulon L, et al. SSR126768A (4-chloro-3-[(3R)-(+)-5-chloro-1-(2,4-dimethoxybenzyl)-3-methyl-2-oxo- 2, 3-dihydro-1H-indol-3-yl]-N-ethyl-N-(3-pyridylmethyl)-benzamide, hydrochloride): a new selective and orally active oxytocin receptor antagonist for the prevention of preterm labor. J Pharmacol Exp Ther 2004;309:414-24
51. Serono Int. Triazoles as oxytocin antagonists. WO2003053437; 2003
52. Serono Int. Pyrrolidine ester derivatives with oxytocin modulating activity. WO2002074741; 2002
53. Serono Int. Pyrrolidine oxadiazole- and thiadiazole oxime derivatives being oxytocin receptors antagonists. WO2002102799; 2002
54. Applied Research Systems ARS. Pyrrolidine derivatives as oxytocin antagonists. US20067115754; 2006
55. Cirillo R, Gillio TE, Schwarz MK, et al. Pharmacology of (2S,4Z)-N-[(2S)-2-hydroxy-2-phenylethyl]-4-(methoxyimino)-1- [(2′-methyl[1,1′-biphenyl]-4-yl) carbonyl]-2-pyrrolidinecarboxamide, a new potent and selective nonpeptide antagonist of the oxytocin receptor. J Pharmacol Exp Ther 2003;306:253-61
56. Pitt GR, Batt AR, Haigh RM, et al. Non-peptide oxytocin agonists. Bioorg Med Chem Lett 2004;14:4585-9
57. Ferring BV. Diazacycloalkanes as oxytocin agonists. WO2003016316; 2003
58. Ferring BV. Oxytocin agonists. WO2003000692; 2003
59. Smith R. Parturition. N Engl J Med 2007;356:271-83
60. Slattery MM, Morrison JJ. Preterm delivery. Lancet 2002;360:1489-97
61. Kam KY, Lamont RF. Developments in the pharmacotherapeutic management of spontaneous preterm labor. Expert Opin Pharmacother 2008;9:1153-68
62. Grignaffini A, Soncini E, Ronzoni E, et al. Clinical practice evaluation of combination of atosiban, ritodrine and ketoprofen for inhibiting preterm labor. Minerva Ginecol 2007;59:481-9
63. Goodwin TM, Paul R, Silver H, et al. The effect of the oxytocin antagonist atosiban on preterm uterine activity in the human. Am J Obstet Gynecol 1994;170:474-8
64. Romero R, Sibai BM, Sanchez-Ramos L, et al. An oxytocin receptor antagonist (atosiban) in the treatment of preterm labor: a randomized, double-blind, placebo-controlled trial with tocolytic rescue. Am J Obstet Gynecol 2000;182:1173-83
65. Papatsonis D, Flenady V, Cole S, et al. Oxytocin receptor antagonists for inhibiting preterm labour. Cochrane Database Syst Rev 2005;CD004452
66. Reinheimer TM, Bee WH, Resendez JC, et al. Barusiban, a new highly potent and long-acting oxytocin antagonist: pharmacokinetic and pharmacodynamic comparison with atosiban in a cynomolgus monkey model of preterm labor. J Clin Endocrinol Metab 2005;90:2275-81
67. Simhan HN, Caritis SN. Prevention of preterm delivery. N Engl J Med 2007;357:477-87
68. Ferring International Center SA. Use of antagonists of oxytocin and/or vasopressin in assisted reproduction. WO2006121362; 2006
69. Cassoni P, Sapino A, Marrocco T, et al. Oxytocin and oxytocin receptors in cancer cells and proliferation. J Neuroendocrinol 2004;16:362-4
70. Copland JA, Jeng YJ, Strakova Z, et al. Demonstration of functional oxytocin receptors in human breast Hs578T cells and their up-regulation through a protein kinase C-dependent pathway. Endocrinology 1999;140:2258-67
71. Bussolati G, Chinol M, Chini B, et al. 111In-labeled 1,4,7,10-tetraazacyclododecane- N,N′,N″,N‴-tetraacetic acid-lys8;-vasotocin: a new powerful radioligand for oxytocin receptor-expressing tumors. Cancer Res 2001;61:4393-7
72. Uvnas-Moberg K, Lundeberg T. Use of oxytocin for the preparation of a pharmaceutical composition against cancer in situ and cervicitis. US20040176284; 2004
73. Quay SC. Long-acting oxytocin analogues for the treatment and prevention of breast cancer and psychiatric disorders. US20040235956; 2004
74. Petersson M, Wiberg U, Lundeberg T, et al. Oxytocin decreases carrageenan induced inflammation in rats. Peptides 2001;22:1479-84
75. Iseri SO, Sener G, Saglam B, et al. Oxytocin protects against sepsis-induced multiple organ damage: role of neutrophils. J Surg Res 2005;126:73-81
76. Uvnas-Moberg K, Lundeberg T. Use of substances with oxytocin activity for the preparation of a pharmaceutical composition against inflammation. WO2003017922; 2003
77. Ferring BV. Use of substances having oxtocin antagonistic properties for the preparation of a medicament for treating hypertension. WO2005070449; 2005
78. Paquin J, Danalache BA, Jankowski M, et al. Oxytocin induces differentiation of P19 embryonic stem cells to cardiomyocytes. Proc Natl Acad Sci USA 2002;99:9550-5
79. Gutkovska J, Paquin J, Danalache B, et al. Oxytocin as cardiomyogenesis inducer and uses thereof. US20060205636; 2006
80. Elabd C, Basillais A, Beaupied H, et al. Oxytocin controls differentiation of human mesenchymal stem cells and reverses osteoporosis. Stem Cells 2008
81. Copland JA, Kirk LI, Simmons DJ, et al. Clinical use of oxytocin alone or in combination to treat bone disorders. US20016333313; 2001
82. Uvnas-Moberg K, Lundegardh B. Use of a substance with oxytocin activity in order to stimulate plant growth. US20060052248; 2006
83. Yeomans DC, Angst MS, Frey WH, Jacobs DI. Methods for treatment of headaches by administration of oxytocin. US20070054843; 2007
84. Nastech Pharmaceutical Company Inc. Compositions and methods for the treatment of psychiatric disorders. US20070032410; 2007
85. Hollander E. Treatment of autism and similar disorders. US20060105939; 2006
86. Nastech Pharmaceutical Company Inc. Pharmaceutical compositions comprising oxytocin or an analog for the treatment of autism. WO2008042452; 2008
87. Uvnas-Moberg KU, Lundeberg T, Petersson M. Use of fragments of oxytocin for the preparation of a pharmaceutical composition in order to create eustasis. US20040259805; 2004
88. Kosfeld M, Heinrichs M, Zak PJ, et al. Oxytocin increases trust in humans. Nature 2005;435:673-6
89. Prevalence of autism spectrum disorders-autism and developmental disabilities monitoring network, 14 sites, United States, 2002. MMWR Surveill Summ 2007;56:12-28
90. Insel TR, O'Brien DJ, Leckman JF. Oxytocin, vasopressin, and autism: is there a connection? Biol Psychiatry 1999;45:145-57
91. Modahl C, Green L, Fein D, et al. Plasma oxytocin levels in autistic children. Biol Psychiatry 1998;43:270-7
92. Marazziti D, Dell'Osso MC. The role of oxytocin in neuropsychiatric disorders. Curr Med Chem 2008;15:698-704
93. Hollander E, Bartz J, Chaplin W,, et al. Oxytocin increases retention of social cognition in autism. Biol Psychiatry 2007;61:498-503
94. Born J, Lange T, Kern W, et al. Sniffing neuropeptides: a transnasal approach to the human brain. Nat Neurosci 2002;5:514-6
95. Baumgartner T, Heinrichs M, Vonlanthen A, et al. Oxytocin shapes the neural circuitry of trust and trust adaptation in humans. Neuron 2008;58:639-50
96. Heinrichs M, Meinlschmidt G, Wippich W, et al. Selective amnesic effects of oxytocin on human memory. Physiol Behav 2004;83:31-8
97. Fisk NM, Atun R. Market failure and the poverty of new drugs in maternal health. PLoS Med 2008;5:e22
98. Opar A. Search for potential autism treatments turns to 'trust hormone'. Nat Med 2008;14:353
99. Ferring BV. Stabilized composition for oral administration of peptides. US19975922680; 1997
100. Abelman Frayne & Schwab. Pharmaceutical composition containing a small or medium size peptide. US20010027177; 2001
101. Nastech Pharmaceutical Co. Tight junction modulating peptides for enhanced mucosal delivery of therapeutic compounds. US20070154449; 2007
102. Aneja A, Tierney E. Autism: the role of cholesterol in treatment. Int Rev Psychiatry 2008;20:165-70
103. Tierney E, Bukelis I, Thompson RE, et al. Abnormalities of cholesterol metabolism in autism spectrum disorders. Am J Med Genet B Neuropsychiatr Genet 2006;141 B:666-8
104. Sikora DM, Pettit-Kekel K, Penfield J, et al. The near universal presence of autism spectrum disorders in children with Smith-Lemli-Opitz syndrome. Am J Med Genet A 2006;140:1511-8
105. Gimpl G, Klein U, Reilander H, et al. Expression of the human oxytocin receptor in baculovirus-infected insect cells: high-affinity binding is induced by a cholesterol-cyclodextrin complex. Biochemistry 1995;34:13794-801
106. Klein U, Gimpl G, Fahrenholz F. Alteration of the myometrial plasma membrane cholesterol content with beta-cyclodextrin modulates the binding affinity of the oxytocin receptor. Biochemistry 1995;34:13784-93
107. Gimpl G, Burger K, Fahrenholz F. Cholesterol as modulator of receptor function. Biochemistry 1997;36:10959-74
108. Guzzi F, Zanchetta D, Cassoni P, et al. Localization of the human oxytocin receptor in caveolin-1 enriched domains turns the receptor-mediated inhibition of cell growth into a proliferative response. Oncogene 2002;21:1658-67
109. Neumann ID. Brain oxytocin: a key regulator of emotional and social behaviours in both females and males. J Neuroendocrinol 2008;20:858-65
110. Mouillac B, Chini B, Balestre MN, et al. The binding site of neuropeptide vasopressin V1a receptor. Evidence for a major localization within transmembrane regions. J Biol Chem 1995;270:25771-7
111. Thibonnier M, Preston JA, Dulin N, et al. The human V3 pituitary vasopressin receptor: ligand binding profile and density-dependent signaling pathways. Endocrinology 1997;138:4109-22
112. Derick S, Cheng LL, Voirol MJ, et al. [1-deamino-4-cyclohexylalanine] arginine vasopressin: a potent and specific agonist for vasopressin V1b receptors. Endocrinology 2002;143:4655-64