Short description: Chemical compound Tarenflurbil Clinical data ATC code| * none Legal status Legal status| * Withdrawn after Phase III Identifiers IUPAC name * (R)-2-(3-Fluoro-4-phenylphenyl)propanoic acid CAS Number| * 51543-40-9 N PubChem CID| * 92337 IUPHAR/BPS| * 7340 ChemSpider| * 83361 N UNII| * 501W00OOWA PDB ligand| * FLR (PDBe, RCSB PDB) Chemical and physical data Formula| C15H13FO2 Molar mass| 244.265 g·mol−1 3D model (JSmol)| * Interactive image SMILES * Fc2cc(ccc2c1ccccc1)[C@H](C(=O)O)C InChI * InChI=1S/C15H13FO2/c1-10(15(17)18)12-7-8-13(14(16)9-12)11-5-3-2-4-6-11/h2-10H,1H3,(H,17,18)/t10-/m1/s1 N * Key:SYTBZMRGLBWNTM-SNVBAGLBSA-N N NY (what is this?) (verify) Tarenflurbil,[1] Flurizan or R-flurbiprofen, is the single enantiomer of the racemate NSAID flurbiprofen. For several years, research and trials for the drug were conducted by Myriad Genetics, to investigate its potential as a treatment for Alzheimer's disease; that investigation concluded in June 2008 when the company announced it would discontinue development of the compound.[2] ## Contents * 1 Mechanism of action * 2 Clinical trials * 3 References * 4 External links ## Mechanism of action At proposed therapeutic concentrations, this molecule lacks anti-inflammatory activity, and does not inhibit either cyclooxygenase 1 (COX-1) or cyclooxygenase 2 (COX-2) enzymes. Only the S-enantiomers of arylpropionic acid NSAID can potently inhibit COX, whereas the R-enantiomers exert almost no COX activity. R-Flurbiprofen is inefficiently converted into S-flurbiprofen, with 1.5% of the R-enantiomer undergoing bioinversion to the S-form. Although this compound lacks activity against COX, studies have shown that this drug is a potent reducer of levels of beta amyloid,[3][4] the main constituent of amyloid plaques in Alzheimer's disease, and therefore there was interest in this drug as a therapeutic agent. ## Clinical trials In 2005, Myriad Genetics reported the results of its Phase II clinical trial of Flurizan; it was the largest ever Alzheimer's drug treatment trial using R-flurbiprofen.[5] Patients were split into three treatment groups, receiving placebo, 400 or 800 mg R-flurbiprofen twice daily for a year. Result from this trial showed that the drug was well tolerated, and positive trends were observed with the 800 mg twice-daily dose in patients with mild Alzheimer's disease. A subgroup of patients that were diagnosed with mild disease, and had high plasma drug levels had significantly less decline in two primary behavioral outcomes (Activities of Daily Living scale (ADCS-ADL) and Global Function (CDR-SB)). Approximately 80 patients enrolled in the optional follow-on study showed continuing benefits with R-flurbiprofen, with increasing positive trends over this period for all primary outcomes after 24 months. On March 5, 2007 Myriad reported final results of the two-year trial, showing that 42% of those 80 patients showed improvement or no decline in one or more of the three primary endpoints of cognition, global function and activities of daily living, compared to a typical 10% of patients on placebo. A Phase III clinical study evaluated 800 mg R-flurbiprofen twice-daily versus placebo for 18 months exclusively in 1800 patients with mild Alzheimer's disease.[6] This second trial concluded in February 2008 with results reported in the summer. After Phase III testing, which included nearly 1,700 patients with mild Alzheimer’s disease treated for 18 months with either Flurizan or placebo, Myrial Genetics concluded that the drug did not improve thinking ability or the ability of patients to carry out daily activities significantly more than those patients with placebo. Peter Meldrum, the chief executive of Myriad, announced on June 30, 2008, that the company will no longer be developing Flurizan.[2] Prior to this termination, Myriad had sold distribution rights in the European Union to Lundbeck for an initial payment of $100 million, which Lundbeck has indicated it will now take as a write-down.[2][7] ## References 1. ↑ www.myriad.com Update on Flurizan. 2. ↑ 2.0 2.1 2.2 Myriad Genetics Reports Results of U.S. Phase 3 Trial of Flurizan in Alzheimer's Disease from the Myriad Genetics website. 3. ↑ "NSAIDs and enantiomers of flurbiprofen target γ-secretase and lower Aβ42 in vivo". J. Clin. Invest. 112 (3): 440–9. August 2003. doi:10.1172/JCI18162. PMID 12897211. 4. ↑ "Selective inhibition of Aβ42 production by NSAID R-enantiomers". J. Neurochem. 83 (4): 1009–12. November 2002. doi:10.1046/j.1471-4159.2002.01195.x. PMID 12421374. 5. ↑ Myriad Genetics Reports Results of Phase 2 Trial of Flurizan in Patients With Alzheimer's Disease, a May 2005 article from the website of Myriad Genetics 6. ↑ www.myriad.com FLURIZAN & Alzheimer's Disease 7. ↑ "Lundbeck Licenses European Rights to Myriad's Alzheimer's Candidate for $100M Upfront". Genetic Engineering & Biotechnology News (Mary Ann Liebert, Inc.): p. 8. 2008-06-15. ## External links * v * t * e Nonsteroidal anti-inflammatory drugs (NSAIDs) (primarily M01A and M02A, also N02BA) Pyrazolones / Pyrazolidines| * Aminophenazone * Ampyrone * Azapropazone * Clofezone * Difenamizole * Famprofazone * Feprazone * Kebuzone * Metamizole * Mofebutazone * Morazone * Nifenazone * Oxyphenbutazone * Phenazone * Phenylbutazone * Propyphenazone * Sulfinpyrazone * Suxibuzone‡ Salicylates| * Aspirin (acetylsalicylic acid)# * Aloxiprin * Benorylate * Carbasalate calcium * Diflunisal * Dipyrocetyl * Ethenzamide * Guacetisal * Magnesium salicylate * Methyl salicylate * Salsalate * Salicin * Salicylamide * Salicylic acid (salicylate) * Sodium salicylate Acetic acid derivatives and related substances| * Aceclofenac * Acemetacin * Alclofenac * Amfenac * Bendazac * Bromfenac * Bumadizone * Bufexamac * Diclofenac * Difenpiramide * Etodolac * Felbinac * Fenclozic acid * Fentiazac * Indometacin * Indometacin farnesil * Isoxepac * Ketorolac * Lonazolac * Oxametacin * Prodolic acid * Proglumetacin * Sulindac * Tiopinac * Tolmetin * Zomepirac† Oxicams| * Ampiroxicam * Droxicam * Isoxicam * Lornoxicam * Meloxicam * Piroxicam * Tenoxicam Propionic acid derivatives (profens)| * Alminoprofen * Benoxaprofen† * Carprofen‡ * Dexibuprofen * Dexketoprofen * Fenbufen * Fenoprofen * Flunoxaprofen * Flurbiprofen * Ibuprofen# * Ibuproxam * Indoprofen† * Ketoprofen * Loxoprofen * Miroprofen * Naproxen * Oxaprozin * Pirprofen * Suprofen * Tarenflurbil * Tepoxalin‡ * Tiaprofenic acid * Vedaprofen‡ * Zaltoprofen * COX-inhibiting nitric oxide donator: Naproxcinod N-Arylanthranilic acids (fenamates)| * Azapropazone * Clonixin * Etofenamate * Flufenamic acid * Flunixin * Meclofenamic acid * Mefenamic acid * Morniflumate * Niflumic acid * Tolfenamic acid * Flutiazin Coxibs| * Apricoxib * Celecoxib * Cimicoxib‡ * Deracoxib‡ * Etoricoxib * Firocoxib‡ * Lumiracoxib† * Mavacoxib‡ * Parecoxib * Robenacoxib‡ * Rofecoxib† * Valdecoxib† Other| * Aminopropionitrile * Benzydamine * Chondroitin sulfate * Diacerein * Fluproquazone * Glucosamine * Glycosaminoglycan * Hyperforin * Nabumetone * Nimesulide * Oxaceprol * Proquazone * Superoxide dismutase/Orgotein * Tenidap Items listed in bold indicate initially developed compounds of specific groups. #WHO-EM †Withdrawn drugs. ‡Veterinary use medications. * v * t * e Prostanoid signaling modulators Receptor (ligands)| | DP (D2)| | DP1| * Agonists: Prostaglandin D2 * Treprostinil * Antagonists: Asapiprant * Laropiprant * Vidupiprant | DP2| * Agonists: Indometacin * Prostaglandin D2 * Antagonists: ADC-3680 * AZD-1981 * Bay U3405 * Fevipiprant * MK-1029 * MK-7246 * QAV-680 * Ramatroban * Setipiprant * Timapiprant * TM30089 * Vidupiprant EP (E2)| | EP1| * Agonists: Beraprost * Enprostil * Iloprost (ciloprost) * Latanoprost * Lubiprostone * Misoprostol * Prostaglandin E1 (alprostadil) * Prostaglandin E2 (dinoprostone) * Sulprostone * Antagonists: AH-6809 * ONO-8130 * SC-19220 * SC-51089 * SC-51322 | EP2| * Agonists: Butaprost * Misoprostol * Prostaglandin E1 (alprostadil) * Prostaglandin E2 (dinoprostone) * Treprostinil * Antagonists: AH-6809 * PF-04418948 * TG 4-155 EP3| * Agonists: Beraprost * Carbacyclin * Cicaprost * Enprostil * Iloprost (ciloprost) * Isocarbacyclin * Latanoprost * Misoprostol * Prostaglandin D2 * Prostaglandin E1 (alprostadil) * Prostaglandin E2 (dinoprostone) * Remiprostol * Sulprostone * Antagonists: L-798106 EP4| * Agonists: Lubiprostone * Misoprostol * Prostaglandin E1 (alprostadil) * Prostaglandin E2 (dinoprostone) * TCS-2510 * Antagonists: Grapiprant * GW-627368 * L-161982 * ONO-AE3-208 Unsorted| * Agonists: 16,16-Dimethyl Prostaglandin E2 * Aganepag * Carboprost * Evatanepag * Gemeprost * Nocloprost * Omidenepag * Prostaglandin F2α (dinoprost) * Simenepag * Taprenepag FP (F2α)| * Agonists: Alfaprostol * Bimatoprost * Carboprost * Cloprostenol * Enprostil * Fluprostenol * Latanoprost * Prostaglandin D2 * Prostaglandin F2α (dinoprost) * Sulotroban * Tafluprost * Travoprost * Unoprostone IP (I2)| * Agonists: ACT-333679 * AFP-07 * Beraprost * BMY-45778 * Carbacyclin * Cicaprost * Iloprost (ciloprost) * Isocarbacyclin * MRE-269 * NS-304 * Prostacyclin (prostaglandin I2, epoprostenol) * Prostaglandin E1 (alprostadil) * Ralinepag * Selexipag * Taprostene * TRA-418 * Treprostinil * Antagonists: RO1138452 TP (TXA2)| * Agonists: Carbocyclic thromboxane A2 * I-BOP * Thromboxane A2 * U-46619 * Vapiprost * Antagonists: 12-HETE * 13-APA * AA-2414 * Argatroban * Bay U3405 * BMS-180,291 * Daltroban * Domitroban * EP-045 * GR-32191 * ICI-185282 * ICI-192605 * Ifetroban * Imitrodast * L-655240 * L-670596 * Linotroban * Mipitroban * ONO-3708 * ONO-11120 * Picotamide * Pinane thromboxane A2 * Ramatroban * Ridogrel * S-145 * Samixogrel * Seratrodast * SQ-28,668 * SQ-29,548 * Sulotroban * Terbogrel * Terutroban * TRA-418 Unsorted| * Arbaprostil * Ataprost * Ciprostene * Clinprost * Cobiprostone * Delprostenate * Deprostil * Dimoxaprost * Doxaprost * Ecraprost * Eganoprost * Enisoprost * Eptaloprost * Esuberaprost * Etiproston * Fenprostalene * Flunoprost * Froxiprost * Lanproston * Limaprost * Luprostiol * Meteneprost * Mexiprostil * Naxaprostene * Nileprost * Nocloprost * Ornoprostil * Oxoprostol * Penprostene * Pimilprost * Piriprost * Posaraprost * Prostalene * Rioprostil * Rivenprost * Rosaprostol * Spiriprostil * Tiaprost * Tilsuprost * Tiprostanide * Trimoprostil * Viprostol Enzyme (inhibitors)| | COX (PTGS)| * Salicylic acids: Aloxiprin * Aspirin (acetylsalicylic acid) * Benorilate (benorylate) * Carbasalate calcium * Diflusinal * Dipyrocetyl * Ethenzamide * Guacetisal * Magnesium salicylate * Mesalazine (5-aminosalicylic acid) * Methyl salicylate * Salacetamide * Salicin * Salicylamide * Salicylate (salicylic acid) * Salsalate * Sodium salicylate * Triflusal; Acetic acids: Aceclofenac * Acemetacin * Aclofenac * Amfenac * Alclofenac * Bendazac * Bromfenac * Bufexamac * Bumadizone * Cinmetacin * Clometacin * Diclofenac * Difenpiramide * Etodolac * Felbinac * Fenclofenac * Fentiazac * Glucametacin * Indometacin (indomethacin) * Indometacin farnesil * Ketorolac * Lonazolac * Mofezolac * Nabumetone * Oxametacin * Oxindanac * Proglumetacin * Sulindac * Sulindac sulfide * Tolmetin * Zidometacin * Zomepirac; Propionic acids: Alminoprofen * Benoxaprofen * Bucloxic acid (blucloxate) * Butibufen * Carprofen * Dexibuprofen * Dexindoprofen * Dexketoprofen * Fenbufen * Fenoprofen * Flunoxaprofen * Flurbiprofen * Ibuprofen * Ibuproxam * Indoprofen * Ketoprofen * Loxoprofen * Miroprofen * Naproxen * Naproxcinod * Oxaprozin * Pirprofen * Pranoprofen * Suprofen * Tarenflurbil * Tepoxalin * Tiaprofenic acid (tiaprofenate) * Vedaprofen; Anthranilic acids (fenamic acids): Etofenamic acid (etofenamate) * Floctafenic acid (floctafenate) * Flufenamic acid (flufenamate) * Meclofenamic acid (meclofenamate) * Mefenamic acid (mefenamate) * Morniflumic acid (morniflumate) * Niflumic acid (niflumate) * Talinflumic acid (talinflumate) * Tolfenamic acid (tolfenamate); Pyrazolones: Azapropazone * Dipyrone * Isopyrin * Oxyphenbutazone * Phenylbutazone; Enolic acids (oxicams): Ampiroxicam * Droxicam * Enolicam * Isoxicam * Lornoxicam * Meloxicam * Piroxicam * Tenoxicam; 4-Aminoquinolines: Antrafenine * Floctafenine * Glafenine; Quinazolines: Fluproquazone * Proquazone; Aminonicotinic acids: Clonixeril * Clonixin * Flunixin; Sulfonanilides: Flosulide * Nimesulide; Aminophenols (anilines): Acetanilide * AM-404 (N-arachidonoylaminophenol) * Bucetin * Paracetamol (acetaminophen) * Parapropamol * Phenacetin * Propacetamol; Selective COX-2 inhibitors (coxibs): Apricoxib * Celecoxib * Cimicoxib * Deracoxib * Etoricoxib * Firocoxib * Lumiracoxib * Mavacoxib * Parecoxib * Polmacoxib * Robenacoxib * Rofecoxib * Tilmacoxib * Valdecoxib; Others/unsorted: Anitrazafen * Clobuzarit * Curcumin * DuP-697 * FK-3311 * Flumizole * FR-122047 * Glimepiride * Hyperforin * Itazigrel * L-655240 * L-670596 * Licofelone * Menatetrenone (vitamin K2) * NCX-466 * NCX-4040 * NS-398 * Pamicogrel * Resveratrol * Romazarit * Rosmarinic acid * Rutecarpine * Satigrel * SC-236 * SC-560 * SC-58125 * Tenidap * Tiflamizole * Timegadine * Trifenagrel * Tropesin | PGD2S| * Retinoids * Selenium (selenium tetrachloride, sodium selenite, selenium disulfide) PGES| HQL-79 PGFS| Bimatoprost PGI2S| Tranylcypromine TXAS| * Camonagrel * Dazmegrel * Dazoxiben * Furegrelate * Isbogrel * Midazogrel * Nafagrel * Nicogrelate * Ozagrel * Picotamide * Pirmagrel * Ridogrel * Rolafagrel * Samixogrel * Terbogrel * U63557A Others| * Precursors: Linoleic acid * γ-Linolenic acid (gamolenic acid) * Dihomo-γ-linolenic acid * Diacylglycerol * Arachidonic acid * Prostaglandin G2 * Prostaglandin H2 See also Receptor/signaling modulators Leukotriene signaling modulators Nuclear receptor modulators 0.00 (0 votes) Original source: https://en.wikipedia.org/wiki/Tarenflurbil. Read more | Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:Tarenflurbil&oldid=2873549" *[CID]: Compound ID *[v]: View this template *[t]: Discuss this template *[e]: Edit this template *[DP (D2)]: Prostaglandin D2 receptor *[DP1]: Prostaglandin D2 receptor 1 *[DP2]: Prostaglandin D2 receptor 2 *[EP (E2)]: Prostaglandin E2 receptor *[EP1]: Prostaglandin EP1 receptor *[EP2]: Prostaglandin EP2 receptor *[EP3]: Prostaglandin EP3 receptor *[EP4]: Prostaglandin EP4 receptor *[FP (F2α)]: Prostaglandin F receptor *[IP (I2)]: Prostacyclin receptor *[TP (TXA2)]: Thromboxane receptor *[COX]: Cyclooxygenase *[PTGS]: prostaglandin G/H synthase *[PGD2S]: Prostaglandin D synthase *[PGES]: Prostaglandin E synthase *[PGFS]: Prostaglandin F synthase *[PGI2S]: Prostacyclin synthase *[TXAS]: Thromboxane A synthase