Summary: Three-carbon cycloparaffin cyclopropane (the structural formula (CH2)3) and its derivatives.

Top Publications

  1. Pitaval A, Leboeuf D, Ceccon J, Echavarren A. Access to the protoilludane core by gold-catalyzed allene-vinylcyclopropane cycloisomerization. Org Lett. 2013;15:4580-3 pubmed publisher
    ..Gold(I)-catalyzed allene-vinylcyclopropane cycloisomerization leads to the tricyclic framework of the protoilludanes in a single step by a reaction that involves a cyclopropane ring expansion and a Prins cyclization. ..
  2. Brenker C, Goodwin N, Weyand I, Kashikar N, Naruse M, Krähling M, et al. The CatSper channel: a polymodal chemosensor in human sperm. EMBO J. 2012;31:1654-65 pubmed publisher
    ..We propose that the CatSper channel complex serves as a polymodal sensor for multiple chemical cues that assist sperm during their voyage across the female genital tract. ..
  3. Milara J, Armengot M, Bañuls P, Tenor H, Beume R, Artigues E, et al. Roflumilast N-oxide, a PDE4 inhibitor, improves cilia motility and ciliated human bronchial epithelial cells compromised by cigarette smoke in vitro. Br J Pharmacol. 2012;166:2243-62 pubmed publisher
  4. Hertel N, Kotchie R, Samyshkin Y, Radford M, Humphreys S, Jameson K. Cost-effectiveness of available treatment options for patients suffering from severe COPD in the UK: a fully incremental analysis. Int J Chron Obstruct Pulmon Dis. 2012;7:183-99 pubmed publisher
    ..The addition of roflumilast to the standard of care regimens is a clinical and cost-effective treatment option for patients with severe COPD, who continue to exacerbate despite existing bronchodilator therapy. ..
  5. Auclair A, Martel J, Assie M, Bardin L, Heusler P, Cussac D, et al. Levomilnacipran (F2695), a norepinephrine-preferring SNRI: profile in vitro and in models of depression and anxiety. Neuropharmacology. 2013;70:338-47 pubmed publisher
    ..It is efficacious in models of anti-depressive/anti-stress activity, with minimal potential for locomotor side effects. ..
  6. Tannheimer S, Sorensen E, Haran A, Mansfield C, Wright C, Salmon M. Additive anti-inflammatory effects of beta 2 adrenoceptor agonists or glucocorticosteroid with roflumilast in human peripheral blood mononuclear cells. Pulm Pharmacol Ther. 2012;25:178-84 pubmed publisher
    ..Addition of roflumilast to either a ?2 adrenoceptor agonist or a glucocorticosteroid may provide superior anti-inflammatory activity and greater efficacy in COPD patients and be dose sparing. ..
  7. Höhne K, Schliessmann S, Kirschbaum A, Plönes T, Müller Quernheim J, Tenor H, et al. Roflumilast-N-oxide induces surfactant protein expression in human alveolar epithelial cells type II. PLoS ONE. 2012;7:e38369 pubmed publisher
    ..Roflumilast-N-oxide fosters the expression of SPs in human AEC-II via increase of intracellular cAMP levels potentially contributing to improved alveolar host defence and enhanced resolution of inflammation...
  8. Seehase S, Lauenstein H, Schlumbohm C, Switalla S, Neuhaus V, Forster C, et al. LPS-induced lung inflammation in marmoset monkeys - an acute model for anti-inflammatory drug testing. PLoS ONE. 2012;7:e43709 pubmed publisher
  9. Kippo T, Hamaoka K, Ryu I. Bromine radical-mediated sequential radical rearrangement and addition reaction of alkylidenecyclopropanes. J Am Chem Soc. 2013;135:632-5 pubmed publisher
    ..A three-component coupling reaction comprising alkylidenecyclopropanes, allylic bromides, and carbon monoxide also proceeded well to give 2-bromo-1,7-dien-5-ones in good yield...

More Information


  1. Ladd C, Sustac Roman D, Charette A. Silver-promoted, palladium-catalyzed direct arylation of cyclopropanes: facile access to spiro 3,3'-cyclopropyl oxindoles. Org Lett. 2013;15:1350-3 pubmed publisher
    ..The kinetic isotope effect was determined and epimerization studies were conducted, suggesting that the formation of a putative Pd-enolate is not operative and that the reaction proceeds via a C-H arylation pathway. ..
  2. Asnis G, Bose A, Gommoll C, Chen C, Greenberg W. Efficacy and safety of levomilnacipran sustained release 40 mg, 80 mg, or 120 mg in major depressive disorder: a phase 3, randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2013;74:242-8 pubmed publisher
    ..Levomilnacipran SR demonstrated significant improvement in depressive symptoms and functioning relative to placebo. In this study, levomilnacipran SR was generally well tolerated. identifier: NCT00969709. ..
  3. Montgomery S, Mansuy L, Ruth A, Bose A, Li H, Li D. Efficacy and safety of levomilnacipran sustained release in moderate to severe major depressive disorder: a randomized, double-blind, placebo-controlled, proof-of-concept study. J Clin Psychiatry. 2013;74:363-9 pubmed publisher
    ..9% vs 20.2%). Levomilnacipran SR demonstrated robust efficacy on all measures and was generally well tolerated. EudraCT number: 2006-002404-34 ..
  4. Jiao L, Yu Z. Vinylcyclopropane derivatives in transition-metal-catalyzed cycloadditions for the synthesis of carbocyclic compounds. J Org Chem. 2013;78:6842-8 pubmed publisher
    ..A tabular summary of applications of the VCP cycloadditions in natural product synthesis is also presented. ..
  5. Parella R, Gopalakrishnan B, Babu S. Auxiliary-enabled Pd-catalyzed direct arylation of methylene C(sp3)-H bond of cyclopropanes: highly diastereoselective assembling of di- and trisubstituted cyclopropanecarboxamides. Org Lett. 2013;15:3238-41 pubmed publisher
    An auxiliary-enabled and Pd(OAc)2-catalyzed direct arylation of C(sp(3))-H bonds of cyclopropanes and production of di- and trisubstituted cyclopropanecarboxamides having contiguous stereocenters are reported...
  6. Goodell J, Poole J, Beeler A, AUBE J, Porco J. Synthesis and reactivity of bicyclo[3.2.1]octanoid-derived cyclopropanes. J Org Chem. 2011;76:9792-800 pubmed publisher
    ..2.1]octanoid scaffolds affords multifunctional, donor-acceptor cyclopropanes. A related photochemical reaction of an iminium ether substrate uncovered an unprecedented aza-di-?-methane ..
  7. Rabe K. Update on roflumilast, a phosphodiesterase 4 inhibitor for the treatment of chronic obstructive pulmonary disease. Br J Pharmacol. 2011;163:53-67 pubmed publisher
  8. Kwak H, Park K, Choi H, Chung K, Lim H, Park H. PDE4 inhibitor, roflumilast protects cardiomyocytes against NO-induced apoptosis via activation of PKA and Epac dual pathways. Cell Signal. 2008;20:803-14 pubmed publisher
    ..Our study suggests a possibility of PDE4 inhibitor roflumilast as a potential therapeutic agent against myocardial ischemia/reperfusion (I/R) injury. ..
  9. Boswell Smith V, Spina D. PDE4 inhibitors as potential therapeutic agents in the treatment of COPD-focus on roflumilast. Int J Chron Obstruct Pulmon Dis. 2007;2:121-9 pubmed
    ..This review will discuss the current standing of PDE4 inhibitors like roflumilast as novel treatments for COPD and the potential for developing nonemetic anti-inflammatory drugs. ..
  10. Calverley P, Sanchez Toril F, McIvor A, Teichmann P, Bredenbroeker D, Fabbri L. Effect of 1-year treatment with roflumilast in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2007;176:154-61 pubmed
    ..However, patients with very severe disease experienced fewer exacerbations with roflumilast. ..
  11. Rob T, Ogi T, Maarisit W, Taira J, Ueda K. Isolation of C?? compounds and a cyclopropane fatty acid from an Okinawan ascidian, Diplosoma sp. Molecules. 2011;16:9972-82 pubmed publisher
    ..The structures of 1-5 were determined by spectroscopic analysis and/or synthesis. Compound 1 inhibited the division of fertilized sea urchin eggs and compound 4 showed mild cytotoxity against HCT116 cells (human colorectal cancer cell). ..
  12. Imbimbo B, Del Giudice E, Colavito D, D Arrigo A, Dalle Carbonare M, Villetti G, et al. 1-(3',4'-Dichloro-2-fluoro[1,1'-biphenyl]-4-yl)-cyclopropanecarboxylic acid (CHF5074), a novel gamma-secretase modulator, reduces brain beta-amyloid pathology in a transgenic mouse model of Alzheimer's disease without causing peripheral toxicity. J Pharmacol Exp Ther. 2007;323:822-30 pubmed
    ..CHF5074 is therefore a promising therapeutic agent for Alzheimer's disease. ..
  13. Wang A, Tan D, Takahashi A, Li T, Harada T. MdERFs, two ethylene-response factors involved in apple fruit ripening. J Exp Bot. 2007;58:3743-8 pubmed
    ..On the basis of concomitant analyses of the expression of some genes related to ripening, the functions of MdERFs and the role of ethylene in the ripening process are discussed. ..
  14. Imbimbo B, Del Giudice E, Cenacchi V, Volta R, Villetti G, Facchinetti F, et al. In vitro and in vivo profiling of CHF5022 and CHF5074 Two beta-amyloid1-42 lowering agents. Pharmacol Res. 2007;55:318-28 pubmed
    ..105) with CHF5022 concentration in the brain. CHF5022 and CHF5074 thus appear to have a promising in vitro and in vivo profile. This warrants further evaluation of their long-term effects on Abeta brain pathology. ..
  15. Bethke T, Böhmer G, Hermann R, Hauns B, Fux R, Mörike K, et al. Dose-proportional intraindividual single- and repeated-dose pharmacokinetics of roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor. J Clin Pharmacol. 2007;47:26-36 pubmed
    ..Repeated oral dosing with roflumilast 250 and 500 microg once daily was well tolerated. ..
  16. Yu X, Rawat R, Shanklin J. Characterization and analysis of the cotton cyclopropane fatty acid synthase family and their contribution to cyclopropane fatty acid synthesis. BMC Plant Biol. 2011;11:97 pubmed publisher
  17. Cerny M, Hanzlik R. Cytochrome P450-catalyzed oxidation of N-benzyl-N-cyclopropylamine generates both cyclopropanone hydrate and 3-hydroxypropionaldehyde via hydrogen abstraction, not single electron transfer. J Am Chem Soc. 2006;128:3346-54 pubmed
    ..Alternatively, hydrogen abstraction at the N-H bond of secondary cyclopropylamines 1 gives a neutral aminyl radical which could undergo rapid ring-opening leading either to enzyme inactivation or 3HP formation. ..
  18. Böhmer G, Gleiter C, Mörike K, Nassr N, Walz A, Lahu G. No dose adjustment on coadministration of the PDE4 inhibitor roflumilast with a weak CYP3A, CYP1A2, and CYP2C19 inhibitor: an investigation using cimetidine. J Clin Pharmacol. 2011;51:594-602 pubmed publisher
    ..These moderate changes indicate that dose adjustment of roflumilast is not required when coadministered with a weak inhibitor of CYP1A2, CYP3A, and CYP2C19, such as cimetidine. ..
  19. Pagès L, Gavaldá A, Lehner M. PDE4 inhibitors: a review of current developments (2005 - 2009). Expert Opin Ther Pat. 2009;19:1501-19 pubmed publisher
  20. Stahl S, Grady M, Moret C, Briley M. SNRIs: their pharmacology, clinical efficacy, and tolerability in comparison with other classes of antidepressants. CNS Spectr. 2005;10:732-47 pubmed
    ..Duloxetine and milnacipran appear better tolerated and essentially devoid of cardiovascular toxicity. ..
  21. Rennard S, Calverley P, Goehring U, Bredenbröker D, Martinez F. Reduction of exacerbations by the PDE4 inhibitor roflumilast--the importance of defining different subsets of patients with COPD. Respir Res. 2011;12:18 pubmed publisher
    ..These observations aided the design of subsequent phase 3 studies that prospectively confirmed the reduction in exacerbations with roflumilast treatment. identifiers: NCT00076089 and NCT00430729. ..
  22. Zheng Q, Nakatsuka A, Itamura H. Involvement of negative feedback regulation in wound-induced ethylene synthesis in 'Saijo' persimmon. J Agric Food Chem. 2006;54:5875-9 pubmed
    ..Out of accord with DK-ACO1 gene expression, ACC oxidase activity was enhanced 48 h after wounding in 1-MCP pretreated tissues, reaching a peak 1.5-fold higher than that in control tissues at 60 h. ..
  23. Sanz M, Cortijo J, Taha M, Cerda Nicolas M, Schatton E, Burgbacher B, et al. Roflumilast inhibits leukocyte-endothelial cell interactions, expression of adhesion molecules and microvascular permeability. Br J Pharmacol. 2007;152:481-92 pubmed
    ..These findings further support earlier observations on the inhibition of inflammatory cell influx and protein extravasation by roflumilast in vivo. ..
  24. Imbimbo B, Hutter Paier B, Villetti G, Facchinetti F, Cenacchi V, Volta R, et al. CHF5074, a novel gamma-secretase modulator, attenuates brain beta-amyloid pathology and learning deficit in a mouse model of Alzheimer's disease. Br J Pharmacol. 2009;156:982-93 pubmed publisher
    ..This novel gamma-secretase modulator is a promising therapeutic agent for Alzheimer's disease. ..
  25. Cortijo J, Iranzo A, Milara X, Mata M, Cerda Nicolas M, Ruiz Sauri A, et al. Roflumilast, a phosphodiesterase 4 inhibitor, alleviates bleomycin-induced lung injury. Br J Pharmacol. 2009;156:534-44 pubmed publisher
    ..Roflumilast prevented the development of bleomycin-induced lung injury, and alleviated the lung fibrotic and vascular remodeling response to bleomycin in a therapeutic protocol, the latter being resistant to glucocorticoids. ..
  26. Burgess J, Oliver B, Poniris M, Ge Q, Boustany S, Cox N, et al. A phosphodiesterase 4 inhibitor inhibits matrix protein deposition in airways in vitro. J Allergy Clin Immunol. 2006;118:649-57 pubmed
    ..Although current asthma therapies are effective in reducing inflammation and symptoms, reversal or prevention of structural changes contributing to remodeling may require additional therapy, which could include PDE4 inhibitors. ..
  27. Wollin L, Marx D, Wohlsen A, Beume R. Roflumilast inhibition of pulmonary leukotriene production and bronchoconstriction in ovalbumin-sensitized and -challenged Guinea pigs. J Asthma. 2005;42:873-8 pubmed
    ..06 mg/kg) and LTB4 (ID50 = 0.05 mg/kg) release versus placebo-treated animals. Roflumilast did not affect LTD4-induced bronchoconstriction. These findings support the role of roflumilast as an anti-inflammatory treatment for asthma. ..
  28. King T, Rao S, Vanderah T, Chen Q, Vardanyan A, Porreca F. Differential blockade of nerve injury-induced shift in weight bearing and thermal and tactile hypersensitivity by milnacipran. J Pain. 2006;7:513-20 pubmed
  29. Nassr N, Lahu G, von Richter O, Reutter F, Knoerzer D, Zech K, et al. Lack of a pharmacokinetic interaction between steady-state roflumilast and single-dose midazolam in healthy subjects. Br J Clin Pharmacol. 2007;63:365-70 pubmed
    ..This finding suggests that roflumilast is unlikely to alter the clearance of drugs that are metabolized by CYP3A4. ..
  30. Lahu G, Nassr N, Herzog R, Elmlinger M, Ruth P, Hinder M, et al. Effect of steady-state enoxacin on single-dose pharmacokinetics of roflumilast and roflumilast N-oxide. J Clin Pharmacol. 2011;51:586-93 pubmed publisher
    ..Roflumilast was well tolerated both alone and in combination with enoxacin. A weak interaction was shown between roflumilast and enoxacin, as mean tPDE4i increased by 25%, but is unlikely to have clinical relevance. ..
  31. Hamblin J, Angell T, Ballantine S, Cook C, Cooper A, Dawson J, et al. Pyrazolopyridines as a novel structural class of potent and selective PDE4 inhibitors. Bioorg Med Chem Lett. 2008;18:4237-41 pubmed publisher
  32. Obata H, Kimura M, Nakajima K, Tobe M, Nishikawa K, Saito S. Monoamine-dependent, opioid-independent antihypersensitivity effects of intrathecally administered milnacipran, a serotonin noradrenaline reuptake inhibitor, in a postoperative pain model in rats. J Pharmacol Exp Ther. 2010;334:1059-65 pubmed publisher
    ..Combined administration of an SNRI with morphine might be a promising treatment to suppress postoperative hypersensitivity...
  33. Carballeira N, Montano N, Vicente J, Rodriguez A. Novel cyclopropane fatty acids from the phospholipids of the Caribbean sponge Pseudospongosorites suberitoides. Lipids. 2007;42:519-24 pubmed
    ..The novel cyclopropyl fatty acids could have originated from the phospholipids of a cyanobacterium living in symbiosis with the sponge. ..
  34. Sabatini F, Petecchia L, Boero S, Silvestri M, Klar J, Tenor H, et al. A phosphodiesterase 4 inhibitor, roflumilast N-oxide, inhibits human lung fibroblast functions in vitro. Pulm Pharmacol Ther. 2010;23:283-91 pubmed publisher
    ..Taken together, these findings indicate that roflumilast N-oxide directly targets human lung fibroblasts, which may at least partially explain the efficacy of roflumilast to mitigate a pulmonary fibrotic response in vivo. ..
  35. Gendreau R, Thorn M, Gendreau J, Kranzler J, Ribeiro S, Gracely R, et al. Efficacy of milnacipran in patients with fibromyalgia. J Rheumatol. 2005;32:1975-85 pubmed
    ..In this Phase II study, milnacipran led to statistically significant improvements in pain and other symptoms of FM. The effect sizes were equal to those previously found with TCA, and the drug was generally well tolerated. ..
  36. Lahu G, Huennemeyer A, Herzog R, McCracken N, Hermann R, Elmlinger M, et al. Effect of repeated dose of erythromycin on the pharmacokinetics of roflumilast and roflumilast N-oxide. Int J Clin Pharmacol Ther. 2009;47:236-45 pubmed
    ..e. mean tPDE4i. No clinically relevant adverse events were observed during the study. Co-administration of erythromycin (a moderate CYP3A4 inhibitor) and roflumilast does not require dose adjustment of roflumilast. ..
  37. Bethke T, Giessmann T, Westphal K, Weinbrenner A, Hauns B, Hauschke D, et al. Roflumilast, a once-daily oral phosphodiesterase 4 inhibitor, lacks relevant pharmacokinetic interactions with inhaled salbutamol when co-administered in healthy subjects. Int J Clin Pharmacol Ther. 2006;44:572-9 pubmed
    ..10 (0.99, 1.21), 1.08 (0.91, 1.28). The combination of both drugs was well tolerated. There were no relevant pharmacokinetic interactions between roflumilast and salbutamol at therapeutically effective doses. ..
  38. Evans P, Inglesby P. Intermolecular rhodium-catalyzed [3+2+2] carbocyclization of alkenylidenecyclopropanes with activated alkynes: regio- and diastereoselective construction of cis-fused bicycloheptadienes. J Am Chem Soc. 2008;130:12838-9 pubmed publisher
    ..The latter feature is particularly significant given that related carbocyclization reactions are often limited in this respect...
  39. Bateman E, Rabe K, Calverley P, Goehring U, Brose M, Bredenbroker D, et al. Roflumilast with long-acting ?2-agonists for COPD: influence of exacerbation history. Eur Respir J. 2011;38:553-60 pubmed publisher
    ..No differences arose in adverse events between these subgroups. Roflumilast may be used to reduce exacerbations and improve dyspnoea and lung function, without increasing adverse events in COPD patients receiving concomitant LABAs. ..
  40. Strünker T, Goodwin N, Brenker C, Kashikar N, Weyand I, Seifert R, et al. The CatSper channel mediates progesterone-induced Ca2+ influx in human sperm. Nature. 2011;471:382-6 pubmed publisher
    ..The identification of CatSper channel blockers will greatly facilitate the study of Ca(2+) signalling in sperm and help to define further the physiological role of progesterone and CatSper. ..
  41. Zhang M, Leng P, Zhang G, Li X. Cloning and functional analysis of 9-cis-epoxycarotenoid dioxygenase (NCED) genes encoding a key enzyme during abscisic acid biosynthesis from peach and grape fruits. J Plant Physiol. 2009;166:1241-52 pubmed publisher
  42. Rabe K, Bateman E, O Donnell D, Witte S, Bredenbröker D, Bethke T. Roflumilast--an oral anti-inflammatory treatment for chronic obstructive pulmonary disease: a randomised controlled trial. Lancet. 2005;366:563-71 pubmed
    ..Long-term studies are needed to fully assess the effect on health-related quality of life. ..
  43. Watkins C. The use of 1-methylcyclopropene (1-MCP) on fruits and vegetables. Biotechnol Adv. 2006;24:389-409 pubmed
  44. Herbst V, Zoller M, Kissling S, Wenzel E, Stutz N, Freyschmidt Paul P. Diphenylcyclopropenone treatment of alopecia areata induces apoptosis of perifollicular lymphocytes. Eur J Dermatol. 2006;16:537-42 pubmed
    ..In addition the replacement with newly activated autoreactive T-cells might be impaired due to a DCP-mediated hindrance of APC emigration. ..
  45. Ceresoli Borroni G, Guidetti P, Amori L, Pellicciari R, Schwarcz R. Perinatal kynurenine 3-hydroxylase inhibition in rodents: pathophysiological implications. J Neurosci Res. 2007;85:845-54 pubmed
    ..Selective inhibitors of this enzyme may therefore provide neuroprotection in newborns and will also be useful for the experimental evaluation of the long-term effects of perinatal KP impairment. ..
  46. Chapman R, House A, Jones H, Richard J, Celly C, Prelusky D, et al. Effect of inhaled roflumilast on the prevention and resolution of allergen-induced late phase airflow obstruction in Brown Norway rats. Eur J Pharmacol. 2007;571:215-21 pubmed
    ..These results support the development of inhaled PDE4 inhibitors for the treatment of asthma and COPD, particularly for the improvement of lung function. ..
  47. Martorana P, Lunghi B, Lucattelli M, De Cunto G, Beume R, Lungarella G. Effect of roflumilast on inflammatory cells in the lungs of cigarette smoke-exposed mice. BMC Pulm Med. 2008;8:17 pubmed publisher
  48. Mease P, Clauw D, Gendreau R, Rao S, Kranzler J, Chen W, et al. The efficacy and safety of milnacipran for treatment of fibromyalgia. a randomized, double-blind, placebo-controlled trial. J Rheumatol. 2009;36:398-409 pubmed publisher
    ..Milnacipran was safe and well tolerated by the majority of patients during 27 weeks of treatment; nausea and headache were the most common adverse events. Milnacipran is safe and effective for the treatment of multiple symptoms of FM. ..
  49. Fabbri L, Calverley P, Izquierdo Alonso J, Bundschuh D, Brose M, Martinez F, et al. Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials. Lancet. 2009;374:695-703 pubmed publisher
    ..These adverse events were associated with increased patient withdrawal. Roflumilast improves lung function in patients with COPD treated with salmeterol or tiotropium, and could become an important treatment for these patients. Nycomed. ..
  50. Huang H, Kim H, Kozekov I, Cho Y, Wang H, Kozekova A, et al. Stereospecific formation of the (R)-gamma-hydroxytrimethylene interstrand N2-dG:N2-dG cross-link arising from the gamma-OH-1,N2-propano-2'-deoxyguanosine adduct in the 5'-CpG-3' DNA sequence. J Am Chem Soc. 2009;131:8416-24 pubmed publisher
    ..The formation of this hydrogen bond may, in part, explain the thermal stability of this carbinolamine interstrand cross-link and the stereochemical preference for the (R) configuration of the cross-link. ..
  51. von Richter O, Lahu G, Huennemeyer A, Herzog R, Zech K, Hermann R. Effect of fluvoxamine on the pharmacokinetics of roflumilast and roflumilast N-oxide. Clin Pharmacokinet. 2007;46:613-22 pubmed
  52. Mbéguié A Mbéguié D, Hubert O, Fils Lycaon B, Chillet M, Baurens F. EIN3-like gene expression during fruit ripening of Cavendish banana (Musa acuminata cv. Grande naine). Physiol Plant. 2008;133:435-48 pubmed publisher
    ..Data presented in this study suggest the importance of a transcriptionally step control in the regulation of EIL genes during banana fruit ripening. ..
  53. Hatzelmann A, Morcillo E, Lungarella G, Adnot S, Sanjar S, Beume R, et al. The preclinical pharmacology of roflumilast--a selective, oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary disease. Pulm Pharmacol Ther. 2010;23:235-56 pubmed publisher
    ..This enables roflumilast to offer effective, oral maintenance treatment for COPD, with an acceptable tolerability profile and the potential to favourably affect the extrapulmonary effects of the disease. ..