F Ivy Carroll

Summary

Affiliation: RTI International
Country: USA

Publications

  1. doi request reprint Designer drugs: a medicinal chemistry perspective
    F Ivy Carroll
    Center for Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, North Carolina 27709 2194, USA
    Ann N Y Acad Sci 1248:18-38. 2012
  2. doi request reprint Antagonists at metabotropic glutamate receptor subtype 5: structure activity relationships and therapeutic potential for addiction
    F Ivy Carroll
    Center for Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, NC 27709 2194, USA
    Ann N Y Acad Sci 1141:221-32. 2008
  3. pmc Synthesis and monoamine transporter binding properties of 2beta-[3'-(substituted benzyl)isoxazol-5-yl]- and 2beta-[3'-methyl-4'-(substituted phenyl)isoxazol-5-yl]-3beta-(substituted phenyl)tropanes
    Chunyang Jin
    Organic and Medicinal Chemistry, Research Triangle Institute, PO Box 12194, Research Triangle Park, NC 27709 2194, USA
    Bioorg Med Chem 16:6682-8. 2008
  4. pmc Synthesis and receptor binding properties of 2beta-alkynyl and 2beta-(1,2,3-triazol)substituted 3beta-(substituted phenyl)tropane derivatives
    Chunyang Jin
    Organic and Medicinal Chemistry, Research Triangle Institute, PO Box 12194, Research Triangle Park, NC 27709 2194, USA
    Bioorg Med Chem 16:5529-35. 2008
  5. doi request reprint Synthesis and in vitro opioid receptor functional antagonism of analogues of the selective kappa opioid receptor antagonist (3R)-7-hydroxy-N-((1S)-1-{[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl}-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoq
    Tingwei Bill Cai
    Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, NC 27709, USA
    J Med Chem 51:1849-60. 2008
  6. doi request reprint Bupropion and bupropion analogs as treatments for CNS disorders
    F Ivy Carroll
    Center for Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, North Carolina, USA Electronic address
    Adv Pharmacol 69:177-216. 2014
  7. pmc Long-acting κ opioid antagonists nor-BNI, GNTI and JDTic: pharmacokinetics in mice and lipophilicity
    Thomas A Munro
    McLean Hospital, Belmont, MA and Department of Psychiatry, Harvard Medical School, Boston, MA, USA
    BMC Pharmacol 12:5. 2012
  8. doi request reprint Interview: interview with frank ivy carroll
    Frank Ivy Carroll
    Center for Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, NC 27709 2194, USA
    Future Med Chem 5:1083-8. 2013
  9. pmc Development of κ opioid receptor antagonists
    F Ivy Carroll
    Center for Organic and Medicinal Chemistry, Research Triangle Institute, P O Box 12194, Research Triangle Park, North Carolina 27709, USA
    J Med Chem 56:2178-95. 2013
  10. ncbi request reprint N-substituted 4beta-methyl-5-(3-hydroxyphenyl)-7alpha-amidomorphans are potent, selective kappa opioid receptor antagonists
    F Ivy Carroll
    Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, North Carolina 27709, USA
    J Med Chem 49:1781-91. 2006

Collaborators

Detail Information

Publications64

  1. doi request reprint Designer drugs: a medicinal chemistry perspective
    F Ivy Carroll
    Center for Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, North Carolina 27709 2194, USA
    Ann N Y Acad Sci 1248:18-38. 2012
    ....
  2. doi request reprint Antagonists at metabotropic glutamate receptor subtype 5: structure activity relationships and therapeutic potential for addiction
    F Ivy Carroll
    Center for Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, NC 27709 2194, USA
    Ann N Y Acad Sci 1141:221-32. 2008
    ....
  3. pmc Synthesis and monoamine transporter binding properties of 2beta-[3'-(substituted benzyl)isoxazol-5-yl]- and 2beta-[3'-methyl-4'-(substituted phenyl)isoxazol-5-yl]-3beta-(substituted phenyl)tropanes
    Chunyang Jin
    Organic and Medicinal Chemistry, Research Triangle Institute, PO Box 12194, Research Triangle Park, NC 27709 2194, USA
    Bioorg Med Chem 16:6682-8. 2008
    ..Molecular modeling studies suggested that the rigid conformation of the isoxazole side chain in 4a-h might play an important role on their low DAT binding affinities...
  4. pmc Synthesis and receptor binding properties of 2beta-alkynyl and 2beta-(1,2,3-triazol)substituted 3beta-(substituted phenyl)tropane derivatives
    Chunyang Jin
    Organic and Medicinal Chemistry, Research Triangle Institute, PO Box 12194, Research Triangle Park, NC 27709 2194, USA
    Bioorg Med Chem 16:5529-35. 2008
    ..9nM at the DAT and K(i) values of 230nM and 620nM at the norepinephrine transporter (NET) and serotonin transporter (5-HTT), respectively...
  5. doi request reprint Synthesis and in vitro opioid receptor functional antagonism of analogues of the selective kappa opioid receptor antagonist (3R)-7-hydroxy-N-((1S)-1-{[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl}-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoq
    Tingwei Bill Cai
    Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, NC 27709, USA
    J Med Chem 51:1849-60. 2008
    ..03 nM at the kappa receptor and 100- and 793-fold selectivity relative to the mu and delta receptors was the most potent and selective kappa opioid receptor antagonist identified...
  6. doi request reprint Bupropion and bupropion analogs as treatments for CNS disorders
    F Ivy Carroll
    Center for Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, North Carolina, USA Electronic address
    Adv Pharmacol 69:177-216. 2014
    ....
  7. pmc Long-acting κ opioid antagonists nor-BNI, GNTI and JDTic: pharmacokinetics in mice and lipophilicity
    Thomas A Munro
    McLean Hospital, Belmont, MA and Department of Psychiatry, Harvard Medical School, Boston, MA, USA
    BMC Pharmacol 12:5. 2012
    ..Recent evidence suggests, instead, that they induce prolonged desensitization of the κ opioid receptor...
  8. doi request reprint Interview: interview with frank ivy carroll
    Frank Ivy Carroll
    Center for Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, NC 27709 2194, USA
    Future Med Chem 5:1083-8. 2013
    ..In 2007, he was inducted into the American Chemical Society Medicinal Chemistry Hall of Fame. Interview conducted by Hannah Coaker, Assistant Commissioning Editor. ..
  9. pmc Development of κ opioid receptor antagonists
    F Ivy Carroll
    Center for Organic and Medicinal Chemistry, Research Triangle Institute, P O Box 12194, Research Triangle Park, North Carolina 27709, USA
    J Med Chem 56:2178-95. 2013
    ....
  10. ncbi request reprint N-substituted 4beta-methyl-5-(3-hydroxyphenyl)-7alpha-amidomorphans are potent, selective kappa opioid receptor antagonists
    F Ivy Carroll
    Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, North Carolina 27709, USA
    J Med Chem 49:1781-91. 2006
    ..3.1]non-7-yl}propanamide (5n, MTHQ) is at least as potent and selective as nor-BNI as a kappa opioid receptor antagonist in the [35S]GTP-gamma-S in vitro functional test...
  11. pmc Development of the dopamine transporter selective RTI-336 as a pharmacotherapy for cocaine abuse
    F Ivy Carroll
    Center for Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, NC 27709, USA
    AAPS J 8:E196-203. 2006
    ..Based on these studies, 3beta-(4-chlorophenyl)-2beta-[3-(4'-methylphenyl)isoxazol-5-yl]tropane (RTI-336) has been selected for preclinical development...
  12. ncbi request reprint Synthesis and pharmacological characterization of nicotinic acetylcholine receptor properties of (+)- and (-)-pyrido-[3,4-b]homotropanes
    F Ivy Carroll
    Organic and Medicinal Chemistry, Research Triangle Institute, P O Box 12194, Research Triangle Park, North Carolina 27709, USA
    J Med Chem 49:3244-50. 2006
    ..07 microg/kg in the tail-flick assay. The reason for this unusual pharmacology is unknown, but it is possible that (-)-1 is acting at a non-epibatidine-sensitive receptor subtype to antagonize nicotine's effects in the tail-flick assay...
  13. ncbi request reprint Synthesis and monoamine transporter binding properties of 2,3-cyclo analogues of 3beta-(4'-aminophenyl)-2beta-tropanemethanol
    F Ivy Carroll
    Center for Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, North Carolina 27709 2194, USA
    J Med Chem 49:4589-94. 2006
    ..These results suggest that the high affinity for 5b and 5e at the DAT and 5-HTT may be due to their specific conformational properties...
  14. ncbi request reprint Effects of dopamine transporter selective 3-phenyltropane analogs on locomotor activity, drug discrimination, and cocaine self-administration after oral administration
    F Ivy Carroll
    Center for Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, NC 27709, USA
    Eur J Pharmacol 553:149-56. 2006
    ..It also reduced self-administration of two infusion doses of cocaine in the rat...
  15. ncbi request reprint Synthesis and pharmacological evaluation of phenylethynyl[1,2,4]methyltriazines as analogues of 3-methyl-6-(phenylethynyl)pyridine
    F Ivy Carroll
    Center for Organic and Medicinal Chemistry, Research Triangle Institute, P O Box 12194, Research Triangle Park, North Carolina 27709, USA
    J Med Chem 50:3388-91. 2007
    ..The most potent compounds were 3-(3-methylphenylethynyl)-5-methyl[1,2,4]triazine (6b), 5-(3-chlorophenylethynyl)-5-methyl[1,2,4]triazine (6c), and 3-(3-bromophenylethynyl)-5-methyl[1,2,4]triazine (6d)...
  16. pmc Synthesis, nicotinic acetylcholine receptor binding, and pharmacological properties of 3'-(substituted phenyl)deschloroepibatidine analogs
    F Ivy Carroll
    Organic and Medicinal Chemistry, Research Triangle Institute, PO Box 12194, Research Triangle Park, NC 27709, USA
    Bioorg Med Chem 16:746-54. 2008
    ..However, they are potent antagonists in nicotine-induced antinociception in the tail-flick test, but weaker than the corresponding 2'-fluoro-3'-(substituted phenyl)deschloroepibatidines...
  17. ncbi request reprint Synthesis and nicotinic acetylcholine receptor binding properties of bridged and fused ring analogues of epibatidine
    F Ivy Carroll
    Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, North Carolina 27709, USA
    J Med Chem 50:6383-91. 2007
    ..Interestingly, N-methylepibatidine, prepared as a standard compound for the study of bridged analogues 6 and 7, was a potent nAChR mixed agonist antagonist...
  18. doi request reprint Synthesis and biological evaluation of bupropion analogues as potential pharmacotherapies for cocaine addiction
    F Ivy Carroll
    Center for Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, North Carolina 27709 2194, USA
    J Med Chem 52:6768-81. 2009
    ....
  19. pmc The synthesis of haptens and their use for the development of monoclonal antibodies for treating methamphetamine abuse
    F Ivy Carroll
    Center for Organic and Medicinal Chemistry, Research Triangle Institute, P O Box 12194, Research Triangle Park, North Carolina 27709, USA
    J Med Chem 52:7301-9. 2009
    ....
  20. pmc Synthesis, nicotinic acetylcholine receptor binding, and antinociceptive properties of 3'-(substituted phenyl)epibatidine analogues. Nicotinic partial agonists
    F Ivy Carroll
    Center for Organic and Medicinal Chemistry, Research Triangle Institute, North Carolina 27709, USA
    J Nat Prod 73:306-12. 2010
    ....
  21. pmc Synthesis and biological evaluation of bupropion analogues as potential pharmacotherapies for smoking cessation
    F Ivy Carroll
    Center for Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, North Carolina 27709 2194, USA
    J Med Chem 53:2204-14. 2010
    ..Analogue 2x with IC(50) values of 31 and 180 nM for DA and NE, respectively, and with IC(50) of 0.62 and 9.8 microm for antagonism of alpha3beta4 and alpha4beta2 nAChRs had the best overall in vitro profile relative to 2a...
  22. pmc Synthesis of 2-(substituted phenyl)-3,5,5-trimethylmorpholine analogues and their effects on monoamine uptake, nicotinic acetylcholine receptor function, and behavioral effects of nicotine
    F Ivy Carroll
    Center for Organic and Medicinal Chemistry, Research Triangle Institute, PO Box 12194, Research Triangle Park, North Carolina 27709 2194, United States
    J Med Chem 54:1441-8. 2011
    ..Collectively, these findings illuminate mechanisms of action of 2 analogues and identify deshydroxybupropion analogues 5a-5h as possibly superior candidates as aids to smoking cessation...
  23. pmc Synthesis of mercapto-(+)-methamphetamine haptens and their use for obtaining improved epitope density on (+)-methamphetamine conjugate vaccines
    F Ivy Carroll
    Center for Organic and Medicinal Chemistry, Research Triangle Institute, P O Box 12194, Research Triangle Park, North Carolina 27709, USA
    J Med Chem 54:5221-8. 2011
    ....
  24. pmc N-substituted cis-4a-(3-hydroxyphenyl)-8a-methyloctahydroisoquinolines are opioid receptor pure antagonists
    F Ivy Carroll
    Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, North Carolina 27709, USA
    J Med Chem 48:8182-93. 2005
    ..27 nM at the kappa opioid receptor with 154- and 46-fold selectivity relative to those of the micro and delta receptors, respectively, possessed the best combination of kappa potency and selectivity...
  25. ncbi request reprint Synthesis and pharmacological characterization of exo-2-(2'-chloro-5-pyridinyl)-7-(endo and exo)-aminobicyclo[2.2.1]heptanes as novel epibatidine analogues
    F Ivy Carroll
    Chemistry and Life Sciences, Research Triangle Institute, P O Box 12194, Research Triangle Park, North Carolina 27709, USA
    J Med Chem 48:7491-5. 2005
    ..Compounds 3a and 3b possessed alpha4beta2 nAChR binding properties similar to those of (-)-nicotine and were nAChR agonists in all four mouse assays...
  26. ncbi request reprint Discovery of the first N-substituted 4beta-methyl-5-(3-hydroxyphenyl)morphan to possess highly potent and selective opioid delta receptor antagonist activity
    F Ivy Carroll
    Chemistry and Life Sciences, Research Triangle Institute, Research Triangle Park, North Carolina 27709, USA
    J Med Chem 47:281-4. 2004
    ..KF4 is also a delta inverse agonist with an IC(50) value of 1.8 nM. To our knowledge, this is the first potent and selective delta opioid receptor antagonist from the 5-phenylmorphan class of opioids...
  27. ncbi request reprint 2002 Medicinal Chemistry Division Award address: monoamine transporters and opioid receptors. Targets for addiction therapy
    F Ivy Carroll
    Chemistry and Life Sciences Group, Research Triangle Institute, P O Box 12194, Research Triangle Park, North Carolina 27709, USA
    J Med Chem 46:1775-94. 2003
  28. ncbi request reprint Pharmacological properties of JDTic: a novel kappa-opioid receptor antagonist
    Ivy Carroll
    Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, North Carolina, USA
    Eur J Pharmacol 501:111-9. 2004
    ..In the U50,488-induced diuresis rat test, JDTic, s.c., suppressed diuretic activity with a greater potency than that of nor-binaltorphimine (nor-BNI). Thus, JDTic is a potent long- and orally acting selective kappa-opioid antagonist...
  29. ncbi request reprint Synthesis, nicotinic acetylcholine receptor binding, and antinociceptive properties of 2-exo-2-(2',3'-disubstituted 5'-pyridinyl)-7-azabicyclo[2.2.1]heptanes: epibatidine analogues
    F Ivy Carroll
    Chemistry and Life Sciences, Research Triangle Institute, P O Box 12194, Research Triangle Park, North Carolina 27709, USA
    J Med Chem 45:4755-61. 2002
    ..2,3-Disubstituted epibatidine analogues possessing a 2'-amino group combined with a 3'-bromo or 3'-iodo group showed in vitro and in vivo nAChR properties similar to nicotine...
  30. ncbi request reprint Monoamine transporter binding, locomotor activity, and drug discrimination properties of 3-(4-substituted-phenyl)tropane-2-carboxylic acid methyl ester isomers
    F Ivy Carroll
    Chemistry and Life Sciences, Research Triangle Institute, Research Triangle Park, North Carolina 27709, USA
    J Med Chem 47:6401-9. 2004
    ..4-11.7 mg/kg, respectively. With the exception of the 2 alpha,3 alpha-isomer, all compounds generalized to cocaine. The 2 beta,3beta-isomers were at least 10-fold more potent than cocaine and the other three sets of isomers in this test...
  31. ncbi request reprint Synthesis, nicotinic acetylcholine receptor binding, and antinociceptive properties of 2'-fluoro-3'-(substituted phenyl)deschloroepibatidine analogues. Novel nicotinic antagonist
    F Ivy Carroll
    Chemistry and Life Sciences, Research Triangle Institute, P O Box 12194, Research Triangle Park, North Carolina 27709, USA
    J Med Chem 47:4588-94. 2004
    ..These compounds also deserve consideration as potential pharmacotherapies for treatment of smoking cessation...
  32. ncbi request reprint Synthesis, nicotinic acetylcholine receptor binding, and antinociceptive properties of 3'-substituted deschloroepibatidine analogues. Novel nicotinic antagonists
    F Ivy Carroll
    Chemistry and Life Sciences, Research Triangle Institute, P O Box 12194, Research Triangle Park, North Carolina 27709, USA
    J Med Chem 48:1221-8. 2005
    ....
  33. ncbi request reprint Synthesis, monoamine transporter binding properties, and behavioral pharmacology of a series of 3beta-(substituted phenyl)-2beta-(3'-substituted isoxazol-5-yl)tropanes
    F Ivy Carroll
    Chemistry and Life Sciences, Research Triangle Institute, Research Triangle Park, North Carolina 27709, USA
    J Med Chem 47:296-302. 2004
    ....
  34. ncbi request reprint Synthesis, nicotinic acetylcholine receptor binding, and antinociceptive properties of 2-exo-2-(2'-substituted-3'-phenyl-5'-pyridinyl)-7-azabicyclo[2.2.1]heptanes. Novel nicotinic antagonist
    F I Carroll
    Chemistry and Life Sciences, Research Triangle Institute, P O Box 12194, Research Triangle Park, North Carolina 27709, USA
    J Med Chem 44:4039-41. 2001
    ..Substitution of different groups at the 2'-position distinguished between agonist and antagonist properties. These results demonstrate that structural requirements for receptor activities and recognition are distinctively different...
  35. ncbi request reprint Synthesis and monoamine transporter binding properties of 3beta-(3',4'-disubstituted phenyl)tropane-2beta-carboxylic acid methyl esters
    F Ivy Carroll
    Chemistry and Life Sciences, Research Triangle Institute, Research Triangle Park, North Carolina 27709, USA
    J Med Chem 48:2767-71. 2005
    ..12 nM) and the 3'-bromo-4'-iodo analogue 3i (K(i) = 0.14 nM) are the most potent analogues at the DAT and 5-HTT, respectively. These compounds will be useful to further characterize the highly interesting behavioral profile of 3b...
  36. ncbi request reprint Synthesis and monoamine transporter binding properties of 3alpha-(substituted phenyl)nortropane-2beta-carboxylic acid methyl esters. Norepinephrine transporter selective compounds
    F Ivy Carroll
    Chemistry and Life Sciences, Research Triangle Institute, Research Triangle Park, North Carolina 27709, USA
    J Med Chem 48:3852-7. 2005
    ..43 nM at the NET and 21- and 55-fold selectivity relative to binding at the dopamine and serotonin transporters. The development of 8d makes available compounds selective for all three transporters from the same structural class...
  37. ncbi request reprint Effects of JDTic, a selective kappa-opioid receptor antagonist, on the development and expression of physical dependence on morphine using a rat continuous-infusion model
    F Ivy Carroll
    Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, North Carolina, USA
    Eur J Pharmacol 524:89-94. 2005
    ..However, it decreased the number of important withdrawal signs designated wet-dog shakes and facial rubs. These data suggest that JDTic may find some application in the treatment of opiate abuse...
  38. ncbi request reprint Synthesis, nicotinic acetylcholine receptor binding, and antinociceptive properties of 2-exo-2-(2'-substituted 5'-pyridinyl)-7-azabicyclo[2.2.1]heptanes. Epibatidine analogues
    F I Carroll
    Chemistry and Life Sciences, Research Triangle Institute, P O Box 12194, Research Triangle Park, North Carolina 27709, USA
    J Med Chem 44:2229-37. 2001
    ..With the exception of 1f and 1g, all the epibatidine analogues are full agonists (tail flick test) in producing antinociception after intrathecal injection in mice...
  39. ncbi request reprint Epibatidine structure-activity relationships
    F Ivy Carroll
    Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, NC 27709, USA
    Bioorg Med Chem Lett 14:1889-96. 2004
    ..Even fewer analogues have received in vivo pharmacological evaluation. In this paper, SAR studies directed toward epibatidine analogues will be reviewed...
  40. ncbi request reprint Synthesis, structural identification, and ligand binding of tropane ring analogs of paroxetine and an unexpected aza-bicyclo[3.2.2]nonane rearrangement product
    Scott P Runyon
    Chemistry and Life Sciences, Research Triangle Institute, 3040 Cornwallis Road, Research Triangle Park, PO Box 12194, North Carolina, NC 27709 2194, USA
    Bioorg Med Chem 13:2439-49. 2005
    ..2.2]nonane derivative 10a...
  41. ncbi request reprint Identification of (3R)-7-hydroxy-N-((1S)-1-[[(3R,4R)-4-(3-hydroxyphenyl)- 3,4-dimethyl-1-piperidinyl]methyl]-2-methylpropyl)-1,2,3,4-tetrahydro- 3-isoquinolinecarboxamide as a novel potent and selective opioid kappa receptor antagonist
    James B Thomas
    Chemistry and Life Sciences, Research Triangle Institute, 3040 Cornwallis Road, Research Triangle Park, North Carolina 27709, USA
    J Med Chem 46:3127-37. 2003
    ..The unique structural features of JDTic will make this compound highly useful in further characterization of the kappa receptor...
  42. ncbi request reprint Synthesis and transporter binding properties of 3beta-[4'-(phenylalkyl, -phenylalkenyl, and -phenylalkynyl)phenyl]tropane-2beta-carboxylic acid methyl esters: evidence of a remote phenyl binding domain on the dopamine transporter
    Bruce E Blough
    Chemistry and Life Sciences, Research Triangle Institute, Research Triangle Park, North Carolina 27709, USA
    J Med Chem 45:4029-37. 2002
    ..82 nM, was the most potent compound studied. This compound possessed K(i) values of 1.19 and 16.5 nM for the serotonin and norepinephrine transporter and is thus a nonselective monoamine uptake inhibitor...
  43. pmc Analogues of (3R)-7-hydroxy-N-[(1S)-1-{[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl}-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxamide (JDTic). Synthesis and in vitro and in vivo opioid receptor antagonist activity
    Scott P Runyon
    Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, North Carolina 27709, USA
    J Med Chem 53:5290-301. 2010
    ..In contrast to 3, where kappa antagonist activity lasted for three weeks, compound 7a did not show any kappa antagonist activity after one week...
  44. ncbi request reprint Synthesis, monoamine transporter binding, properties, and functional monoamine uptake activity of 3beta-[4-methylphenyl and 4-chlorophenyl]-2 beta-[5-(substituted phenyl)thiazol-2-yl]tropanes
    Paul K Gong
    Center for Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, North Carolina 27709 2194, USA
    J Med Chem 50:3686-95. 2007
    ..The most potent and selective analog in the functional monoamine uptake inhibition test was 3beta-(4-methylphenyl-2 beta-[5-(3-nitrophenyl)thiazol-2-yl]tropane (4p)...
  45. pmc Discovery of N-{4-[(3-hydroxyphenyl)-3-methylpiperazin-1-yl]methyl-2-methylpropyl}-4-phenoxybenzamide analogues as selective kappa opioid receptor antagonists
    Chad M Kormos
    Center for Organic and Medicinal Chemistry, Research Triangle Institute, P O Box 12194, Research Triangle Park, North Carolina 27709, USA
    J Med Chem 56:4551-67. 2013
    ..An SAR study based on 11a provided 28 novel analogues. Evaluation of these 28 compounds in the [(35)S]GTPγS binding assay showed that several of the analogues were potent and selective κ opioid receptor antagonists...
  46. ncbi request reprint Discovery of an opioid kappa receptor selective pure antagonist from a library of N-substituted 4beta-methyl-5-(3-hydroxyphenyl)morphans
    James B Thomas
    Chemistry and Life Sciences, Research Triangle Institute, Research Triangle Park, NC 27709, USA
    J Med Chem 45:3524-30. 2002
    ....
  47. ncbi request reprint Importance of phenolic address groups in opioid kappa receptor selective antagonists
    James B Thomas
    Chemistry and Life Sciences, Research Triangle Institute, Research Triangle Park, North Carolina 27709, USA
    J Med Chem 47:1070-3. 2004
    ..The structural flexibility of the former class of compound relative to the latter is postulated to underlie the difference...
  48. pmc A new synthesis of the ORL-1 antagonist 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one (J-113397) and activity in a calcium mobilization assay
    Emilie D Smith
    Organic and Medicinal Chemistry, Research Triangle Institute, PO Box 12194, Research Triangle Park, NC 27709, USA
    Bioorg Med Chem 16:822-9. 2008
    ..J-113397 has a K(e)=0.85nM in an ORL-1 calcium mobilization assay and is 89-, 887-, and 227-fold selective for the ORL-1 receptor relative to the mu, delta, and kappa opioid receptors...
  49. doi request reprint Synthesis and in vitro opioid receptor functional antagonism of methyl-substituted analogues of (3R)-7-hydroxy-N-[(1S)-1-{[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl}-2-methylpropyl]-1,2,3,4-tetrahydro-3-isoquinolinecarboxamide (JDTic)
    Juan Pablo Cueva
    Center for Organic and Medicinal Chemistry, Research Triangle Institute, Post Office Box 12194, Research Triangle Park, North Carolina 27709 2194, USA
    J Med Chem 52:7463-72. 2009
    ..037 nM at the kappa receptor. All three compounds were selective for the kappa receptor relative to the micro and delta receptors. Overall, the results from this study highlight those areas that are tolerant to substitution on 3...
  50. ncbi request reprint Synthesis and monoamine transporter binding properties of 2,3-diaryltropanes
    Sharadsrikar V Kotturi
    Center for Organic and Medicinal Chemistry, Research Triangle Institute, P O Box 12194, Research Triangle Park, North Carolina 27709, USA
    J Med Chem 48:7437-44. 2005
    ..23 nM at the DAT with 289- and 185-fold selectivity for the DAT relative to the NET and 5-HTT. The 2alpha,3alpha-diaryltropanes were much less potent at all three transporters than 2beta,3beta-diaryltropanes...
  51. ncbi request reprint Highly potent and selective phenylmorphan-based inverse agonists of the opioid delta receptor
    James B Thomas
    Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, North Carolina 27709, USA
    J Med Chem 49:5597-609. 2006
    ....
  52. pmc Positive allosteric modulation of the human cannabinoid (CB) receptor by RTI-371, a selective inhibitor of the dopamine transporter
    Hernan A Navarro
    RTI International, Research Triangle Park, NC 27709 2194, USA
    Br J Pharmacol 156:1178-84. 2009
    ..Initial screening identified RTI-371 as a positive allosteric modulator of the human CB(1) (hCB(1)) receptor...
  53. pmc Development of 3-phenyltropane analogues with high affinity for the dopamine and serotonin transporters and low affinity for the norepinephrine transporter
    Chunyang Jin
    Center for Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, North Carolina 27709 2194, USA
    J Med Chem 51:8048-56. 2008
    ..5 nM for the DAT and K(i) values of 3.5 and 2040 nM for the 5-HTT and NET, respectively, is the most potent and selective compound for the DAT and 5-HTT relative to the NET in this study...
  54. pmc Synthesis and nicotinic acetylcholine receptor in vitro and in vivo pharmacological properties of 2'-fluoro-3'-(substituted phenyl)deschloroepibatidine analogues of 2'-fluoro-3'-(4-nitrophenyl)deschloroepibatidine
    Pauline Ondachi
    Center for Organic and Medicinal Chemistry, Research Triangle Institute, P O Box 12194, Research Triangle Park, NC 27709, USA
    J Med Chem 55:6512-22. 2012
    ....
  55. doi request reprint Synthesis and evaluation of 1,2,4-methyltriazines as mGluR5 antagonists
    Jeremy P Olson
    Center for Organic and Medicinal Chemistry, Research Triangle Institute, P O Box 12194, Research Triangle Park, Durham, North Carolina 27709, USA
    Org Biomol Chem 9:4276-86. 2011
    ..Compound 2-(4-fluorophenyl-5-[2-(5-methyl[1,2,4]triazine-3-yl)ethynyl]benzonitrile (5f) with an IC(50) of 28.2 nM was the most potent analogue...
  56. doi request reprint Nicotinic acetylcholine receptor efficacy and pharmacological properties of 3-(substituted phenyl)-2β-substituted tropanes
    F Ivy Carroll
    Center for Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, North Carolina 27709 2194, United States
    J Med Chem 53:8345-53. 2010
    ..We have identified new compounds that have utility as research tools and possible promise for treatment of nicotine dependence. ..
  57. pmc 4β-Methyl-5-(3-hydroxyphenyl)morphan opioid agonist and partial agonist derived from a 4β-methyl-5-(3-hydroxyphenyl)morphan pure antagonist
    F Ivy Carroll
    Center for Organic and Medicinal Chemistry, Research Triangle Institute, P O Box 12194, Research Triangle Park, North Carolina 27709, United States
    J Med Chem 56:8826-33. 2013
    ....
  58. doi request reprint Emergence and properties of spice and bath salts: a medicinal chemistry perspective
    Anita H Lewin
    Center for Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, NC, USA Electronic address
    Life Sci 97:9-19. 2014
    ..This review describes the emergence and properties of these two groups of "legal highs" from a medicinal chemist's perspective. ..
  59. doi request reprint Synthesis, nicotinic acetylcholine receptor binding, and antinociceptive properties of 2'-fluoro-3'-(substituted pyridinyl)-7-deschloroepibatidine analogues
    Pauline W Ondachi
    Center for Organic and Medicinal Chemistry, Research Triangle Institute, P O Box 12194, Research Triangle Park, North Carolina 27709, United States
    J Med Chem 57:836-48. 2014
    ..In addition, 5g was a nicotine antagonist in both the tail-flick and hot-plate tests, whereas 8a was an antagonist only in the tail-flick test. ..
  60. doi request reprint Hydrolytic instability of the important orexin 1 receptor antagonist SB-334867: possible confounding effects on in vivo and in vitro studies
    Charles J McElhinny
    Research Triangle Institute, 3040 Cornwallis Road, Research Triangle Park, NC 27709, USA
    Bioorg Med Chem Lett 22:6661-4. 2012
    ....
  61. pmc Synthesis, nicotinic acetylcholine receptor binding, antinociceptive and seizure properties of methyllycaconitine analogs
    F Ivy Carroll
    Chemistry and Life Sciences, Research Triangle Institute, Research Triangle Park, NC 27709, USA
    Bioorg Med Chem 15:678-85. 2007
    ....
  62. pmc Synthesis and structure-activity relationship of 3beta-(4-alkylthio, -methylsulfinyl, and -methylsulfonylphenyl)tropane and 3beta-(4-alkylthiophenyl)nortropane derivatives for monoamine transporters
    Chunyang Jin
    Organic and Medicinal Chemistry, Research Triangle Institute, PO Box 12194, Research Triangle Park, NC 27709 2194, USA
    Bioorg Med Chem 17:5126-32. 2009
    ..However, none of the compounds showed selectivity similar to 5 for both the DAT and 5-HTT relative to the NET. This study provided useful SAR information for rational design of potent and selective monoamine transporter inhibitors...
  63. ncbi request reprint Dopamine transporter ligands: recent developments and therapeutic potential
    Scott P Runyon
    Organic and Medicinal Chemistry, Research Triangle Institute, Research Triangle Park, North Carolina 27709, USA
    Curr Top Med Chem 6:1825-43. 2006
    ..A number of the compounds showed decreased cocaine maintained responding in rhesus monkeys trained to self-administer cocaine. One compound, GBR 12,909, was evaluated in a Phase 1 clinical trial...
  64. pmc Synthesis of hemopressin peptides by classical solution phase fragment condensation
    P Anantha Reddy
    Center for Organic and Medicinal Chemistry, Discovery Sciences Research Triangle Institute, Research Triangle Park, NC 27709 2194, USA
    Int J Pept 2012:186034. 2012
    ....

Research Grants42

  1. Selective Opioid Antagonists as Medications for Drug Abuse
    Frank Ivy Carroll; Fiscal Year: 2010
    ..This application addresses these problems by proposing to identify and develop selective ? opioid receptor antagonists as new pharmacotherapies to treat patients addicted to drugs of abuse. ..
  2. SELECTIVE OPIOID ANTAGONIST AS MEDICATION FOR DRUG ABUSE
    Frank Carroll; Fiscal Year: 2007
    ..Compounds that are potent delta selective opioid receptor inverse agonists will be evaluated by Dr. Chris Evans (UCLA) in a chronic antinociception rat model. ..
  3. DEVELOPMENT OF LIGANDS FOR NICOTINIC RECEPTORS
    Frank Carroll; Fiscal Year: 2006
    ....
  4. Development of Pharmacotherapies for Nicotine Addiction
    Frank Carroll; Fiscal Year: 2005
    ....
  5. COCAINE: A STUDY OF THE BIOCHEMICAL MECHANISM OF ACTION
    Frank Carroll; Fiscal Year: 2007
    ..abstract_text> ..
  6. Design and Development of Pharmacotherapies for Treating Stimulant Abuse
    Frank Ivy Carroll; Fiscal Year: 2010
    ..3) To continue on a limited basis our development of selected 3-phenyltropane analogs as second-generation pharmacotherapies to treat cocaine addiction. ..
  7. DEVELOPMENT OF LIGANDS FOR NICOTINIC RECEPTORS
    Frank Ivy Carroll; Fiscal Year: 2010
    ..This application addresses this problem by proposing studies to develop competitive antagonists and partial agonists as well as allosteric modulators of nicotinic acetylcholine receptors as new pharmacotherapies to treat smokers. ..
  8. DEVELOPMENT OF LIGANDS FOR NICOTINIC RECEPTORS
    Frank Carroll; Fiscal Year: 2009
    ..This application addresses this problem by proposing studies to develop competitive antagonists and partial agonists as well as allosteric modulators of nicotinic acetylcholine receptors as new pharmacotherapies to treat smokers. ..
  9. COCAINE: A STUDY OF THE BIOCHEMICAL MECHANISM OF ACTION
    Frank Carroll; Fiscal Year: 1991
    ....
  10. SELECTIVE OPIOID ANTAGONIST AS MEDICATION FOR DRUG ABUSE
    Frank Carroll; Fiscal Year: 2003
    ..abstract_text> ..
  11. DEVELOPMENT OF LIGANDS FOR NICOTINIC RECEPTORS
    Frank Carroll; Fiscal Year: 2001
    ..5) The potency of the epibatidine analogs prepared at RTI in activating expressed alpha4beta2 receptors was shown by studies at MCV to correlate well with the K-app binding affinities. ..
  12. NOVEL PHARMACOTHERAPIES FOR COCAINE DEPENDENCE
    Frank Carroll; Fiscal Year: 2001
    ..An ideal candidate compound would not only have efficacy in the preclinical models but would be safe, orally active, and potent, would not show tolerance or sensitization, and if abusable, would be less so than cocaine. ..