PRX-08066

PRX-08066
Identifiers

IUPAC name 5-((4-(6-chlorothieno[2,3-d]pyrimidin-4-ylamino)piperidin-1-yl)methyl)-2-fluorobenzonitrile
CAS Number	866206-54-4^Y
PubChem CID	11502243
ChemSpider	9677045
UNII	82SK298EBU
CompTox Dashboard (EPA)	DTXSID60235710
Chemical and physical data
Formula	C₁₉H₁₇ClFN₅S
Molar mass	401.89 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES s3c2ncnc(c2cc3Cl)NC4CCN(CC4)Cc(ccc1F)cc1C#N

PRX-08066 is a drug discovered and developed by Predix (later Epix) Pharmaceuticals [Dale S. Dhanoa et al. Patent US 7,030,240 B2], which acts as a potent and selective antagonist at the serotonin 5-HT_2B receptor, with a 5-HT_2B binding affinity (K_i) of 3.4nM, and high selectivity over the closely related 5-HT_2A and 5-HT_2C receptors and other receptor targets. PRX-08066 and other selective 5-HT_2B antagonists are being researched for the treatment of pulmonary arterial hypertension, following the discovery that the potent 5-HT_2B agonist norfenfluramine produces pulmonary arterial hypertension and subsequent heart valve damage. In animal studies, PRX-08066 has been found to reduce several key indicators of pulmonary arterial hypertension and improved cardiac output, with similar efficacy to established drugs for this condition such as bosentan, sildenafil, beraprost and iloprost. ^[1] It is also being researched for potential anti-cancer applications, due to its ability to inhibit fibroblast activation.^[2]

References

^ Porvasnik SL, Germain S, Embury J, Gannon KS, Jacques V, Murray J, Byrne BJ, Shacham S, Al-Mousily F (August 2010). "PRX-08066, a novel 5-hydroxytryptamine receptor 2B antagonist, reduces monocrotaline-induced pulmonary arterial hypertension and right ventricular hypertrophy in rats". The Journal of Pharmacology and Experimental Therapeutics. 334 (2): 364–72. doi:10.1124/jpet.109.165001. PMID 20430844. S2CID 206500649.
^ Svejda B, Kidd M, Giovinazzo F, Eltawil K, Gustafsson BI, Pfragner R, Modlin IM (June 2010). "The 5-HT(2B) receptor plays a key regulatory role in both neuroendocrine tumor cell proliferation and the modulation of the fibroblast component of the neoplastic microenvironment". Cancer. 116 (12): 2902–12. doi:10.1002/cncr.25049. PMID 20564397.

Serotonin receptor modulators

5-HT₁

5-HT_1A

Agonists: 8-OH-DPAT Adatanserin Amphetamine Antidepressants (e.g., etoperidone, hydroxynefazodone, nefazodone, trazodone, triazoledione, vilazodone, vortioxetine) Atypical antipsychotics (e.g., aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, lurasidone, quetiapine, ziprasidone) Azapirones (e.g., buspirone, eptapirone, gepirone, perospirone, tandospirone) Bay R 1531 Befiradol BMY-14802 Cannabidiol Dimemebfe Dopamine Ebalzotan Eltoprazine Enciprazine Ergolines (e.g., bromocriptine, cabergoline, dihydroergotamine, ergotamine, lisuride, LSD, methylergometrine (methylergonovine), methysergide, pergolide) F-11,461 F-12826 F-13714 F-14679 F-15063 F-15,599 Flesinoxan Flibanserin Flumexadol Hypidone Lesopitron LY-293284 LY-301317 mCPP MKC-242 Naluzotan NBUMP Osemozotan Oxaflozane Pardoprunox Piclozotan Rauwolscine Repinotan Roxindole RU-24,969 S-14,506 S-14671 S-15535 Sarizotan Serotonin (5-HT) SSR-181507 Sunepitron Tryptamines (e.g., 5-CT, 5-MeO-DMT, 5-MT, bufotenin, DMT, indorenate, N-Me-5-HT, psilocin, psilocybin) TGBA01AD U-92,016-A Urapidil Vilazodone Xaliproden Yohimbine
Antagonists: Atypical antipsychotics (e.g., iloperidone, risperidone, sertindole) AV965 Beta blockers (e.g., alprenolol, carteolol, cyanopindolol, iodocyanopindolol, isamoltane, oxprenolol, penbutolol, pindobind, pindolol, propranolol, tertatolol) BMY-7,378 CSP-2503 Dotarizine Ergolines (e.g., metergoline) FCE-24379 Flopropione GR-46611 Isamoltane Lecozotan Mefway Metitepine (methiothepin) MIN-117 (WF-516) MPPF NAN-190 Robalzotan S-15535 SB-649,915 SDZ 216-525 Spiperone Spiramide Spiroxatrine UH-301 WAY-100135 WAY-100635 Xylamidine
Unknown/unsorted: Acetryptine Carvedilol Ergolines (e.g., ergometrine (ergonovine))

5-HT_1B

Agonists: Anpirtoline CGS-12066A CP-93129 CP-94253 CP-122,288 CP-135807 Eltoprazine Ergolines (e.g., bromocriptine, dihydroergotamine, ergotamine, methylergometrine (methylergonovine), methysergide, pergolide) mCPP RU-24,969 Serotonin (5-HT) Triptans (e.g., avitriptan, donitriptan, eletriptan, sumatriptan, zolmitriptan) TFMPP Tryptamines (e.g., 5-BT, 5-CT, 5-MT, DMT) Vortioxetine
Antagonists: AR-A000002 Beta blockers (e.g., alprenolol, carteolol, isamoltane, oxprenolol, penbutolol, propranolol, tertatolol) Elzasonan Ergolines (e.g., metergoline) GR-127935 Isamoltane LY-393558 Metitepine (methiothepin) SB-216641 SB-224289 SB-236057 Yohimbine
Unknown/unsorted: Ergolines (e.g., cabergoline, ergometrine (ergonovine), lisuride)

5-HT_1D

Agonists: CP-122,288 CP-135807 CP-286601 Ergolines (e.g., bromocriptine, cabergoline, dihydroergotamine, ergotamine, LSD, methysergide) GR-46611 L-694247 L-772405 mCPP PNU-109291 PNU-142633 Serotonin (5-HT) TGBA01AD Triptans (e.g., almotriptan, avitriptan, donitriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan) Tryptamines (e.g., 5-BT, 5-CT, 5-Et-DMT, 5-MT, 5-(nonyloxy)tryptamine, DMT)
Antagonists: Alniditan BRL-15,572 Elzasonan Ergolines (e.g., metergoline) GR-127935 Ketanserin LY-310762 LY-367642 LY-393558 LY-456219 LY-456220 Metitepine (methiothepin) Mianserin Ritanserin Yohimbine Ziprasidone
Unknown/unsorted: Acetryptine Ergolines (e.g., lisuride, lysergol, pergolide)

5-HT_1E

Agonists: BRL-54443 Ergolines (e.g., methysergide) Serotonin (5-HT) Triptans (e.g., eletriptan) Tryptamines (e.g., tryptamine)
Antagonists: Metitepine (methiothepin)
Unknown/unsorted: Ergolines (e.g., ergometrine (ergonovine), lysergol, methylergometrine (methylergonovine)

5-HT_1F

Agonists: BRL-54443 CP-122,288 Ergolines (e.g., bromocriptine, lysergol, methylergometrine (methylergonovine) methysergide) Lasmiditan LY-334370 Serotonin (5-HT) Triptans (e.g., eletriptan, naratriptan, sumatriptan) Tryptamines (e.g., 5-MT)
Antagonists: Metitepine (methiothepin) Mianserin

5-HT₂

5-HT_2A

Agonists: 25H/NB series (e.g., 25I-NBF, 25I-NBMD, 25I-NBOH, 25I-NBOMe, 25B-NBOMe, 25C-NBOMe, 25TFM-NBOMe, 2CBCB-NBOMe, 25CN-NBOH, 2CBFly-NBOMe) 2Cs (e.g., 2C-B, 2C-E, 2C-I, 2C-T-2, 2C-T-7, 2C-T-21) 2C-B-FLY 2CB-Ind 5-Methoxytryptamines (5-MeO-DET, 5-MeO-DiPT, 5-MeO-DMT, 5-MeO-DPT, 5-MT) α-Alkyltryptamines (e.g., 5-Cl-αMT, 5-Fl-αMT, 5-MeO-αET, 5-MeO-αMT, α-Me-5-HT, αET, αMT) AL-34662 AL-37350A Bromo-DragonFLY Dimemebfe DMBMPP DOx (e.g., DOB, DOC, DOI, DOM) Efavirenz Ergolines (e.g., 1P-LSD, ALD-52, bromocriptine, cabergoline, ergine (LSA), ergometrine (ergonovine), ergotamine, lisuride, LA-SS-Az, LSB, LSD, LSD-Pip, LSH, LSP, methylergometrine (methylergonovine), pergolide) Flumexadol IHCH-7113 Jimscaline Lorcaserin MDxx (e.g., MDA (tenamfetamine), MDMA (midomafetamine), MDOH, MMDA) O-4310 Oxaflozane PHA-57378 PNU-22394 PNU-181731 RH-34 SCHEMBL5334361 Phenethylamines (e.g., lophophine, mescaline) Piperazines (e.g., BZP, quipazine, TFMPP) Serotonin (5-HT) TCB-2 TFMFly Tryptamines (e.g., 5-BT, 5-CT, bufotenin, DET, DiPT, DMT, DPT, psilocin, psilocybin, tryptamine)
Antagonists: 5-I-R91150 5-MeO-NBpBrT AC-90179 Adatanserin Altanserin Antihistamines (e.g., cyproheptadine, hydroxyzine, ketotifen, perlapine) AMDA Atypical antipsychotics (e.g., amperozide, aripiprazole, asenapine, blonanserin, brexpiprazole, carpipramine, clocapramine, clorotepine, clozapine, fluperlapine, gevotroline, iloperidone, lurasidone, melperone, mosapramine, ocaperidone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, zicronapine, ziprasidone, zotepine) Chlorprothixene Cinanserin CSP-2503 Deramciclane Dotarizine Eplivanserin Ergolines (e.g., amesergide, LY-53857, LY-215,840, mesulergine, metergoline, methysergide, sergolexole) Fananserin Flibanserin Glemanserin Irindalone Ketanserin KML-010 Landipirdine LY-393558 mCPP Medifoxamine Metitepine (methiothepin) MIN-117 (WF-516) Naftidrofuryl Nantenine Nelotanserin Opiranserin (VVZ-149) Pelanserin Phenoxybenzamine Pimavanserin Pirenperone Pizotifen Pruvanserin Rauwolscine Ritanserin Roluperidone S-14671 Sarpogrelate Serotonin antagonists and reuptake inhibitors (e.g., etoperidone, hydroxynefazodone, lubazodone, mepiprazole, nefazodone, triazoledione, trazodone) SR-46349B TGBA01AD Teniloxazine Temanogrel Tetracyclic antidepressants (e.g., amoxapine, aptazapine, esmirtazapine, maprotiline, mianserin, mirtazapine) Tricyclic antidepressants (e.g., amitriptyline) Typical antipsychotics (e.g., chlorpromazine, fluphenazine, haloperidol, loxapine, perphenazine, pimozide, pipamperone, prochlorperazine, setoperone, spiperone, spiramide, thioridazine, thiothixene, trifluoperazine) Volinanserin Xylamidine Yohimbine
Unknown/unsorted: Ergolines (e.g., dihydroergotamine, nicergoline)

5-HT_2B

Agonists: 4-Methylaminorex Aminorex Amphetamines (e.g., chlorphentermine, cloforex, dexfenfluramine, fenfluramine, levofenfluramine, norfenfluramine) BW-723C86 DOx (e.g., DOB, DOC, DOI, DOM) Ergolines (e.g., cabergoline, dihydroergocryptine, dihydroergotamine, ergotamine, methylergometrine (methylergonovine), methysergide, pergolide) Lorcaserin MDxx (e.g., MDA (tenamfetamine), MDMA (midomafetamine), MDOH, MMDA) Piperazines (e.g., TFMPP) PNU-22394 Ro60-0175 Serotonin (5-HT) Tryptamines (e.g., 5-BT, 5-CT, 5-MT, α-Me-5-HT, bufotenin, DET, DiPT, DMT, DPT, psilocin, psilocybin, tryptamine)
Antagonists: Agomelatine Atypical antipsychotics (e.g., amisulpride, aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, N-desalkylquetiapine (norquetiapine), N-desmethylclozapine (norclozapine), olanzapine, pipamperone, quetiapine, risperidone, ziprasidone) Cyproheptadine EGIS-7625 Ergolines (e.g., amesergide, bromocriptine, lisuride, LY-53857, LY-272015, mesulergine) Ketanserin LY-393558 mCPP Metadoxine Metitepine (methiothepin) Pirenperone Pizotifen Propranolol PRX-08066 Rauwolscine Ritanserin RS-127445 Sarpogrelate SB-200646 SB-204741 SB-206553 SB-215505 SB-221284 SB-228357 SDZ SER-082 Tegaserod Tetracyclic antidepressants (e.g., amoxapine, mianserin, mirtazapine) Trazodone Typical antipsychotics (e.g., chlorpromazine) TIK-301 Yohimbine
Unknown/unsorted: Ergolines (e.g., ergometrine (ergonovine))

5-HT_2C

Agonists: 2Cs (e.g., 2C-B, 2C-E, 2C-I, 2C-T-2, 2C-T-7, 2C-T-21) 5-Methoxytryptamines (5-MeO-DET, 5-MeO-DiPT, 5-MeO-DMT, 5-MeO-DPT, 5-MT) α-Alkyltryptamines (e.g., 5-Cl-αMT, 5-Fl-αMT, 5-MeO-αET, 5-MeO-αMT, α-Me-5-HT, αET, αMT) A-372159 AL-38022A Alstonine CP-809101 Dimemebfe DOx (e.g., DOB, DOC, DOI, DOM) Ergolines (e.g., ALD-52, cabergoline, dihydroergotamine, ergine (LSA), ergotamine, lisuride, LA-SS-Az, LSB, LSD, LSD-Pip, LSH, LSP, pergolide) Flumexadol Lorcaserin MDxx (e.g., MDA (tenamfetamine), MDMA (midomafetamine), MDOH, MMDA) MK-212 ORG-12962 ORG-37684 Oxaflozane PHA-57378 Phenethylamines (e.g., lophophine, mescaline) Piperazines (e.g., aripiprazole, BZP, mCPP, quipazine, TFMPP) PNU-22394 PNU-181731 Ro60-0175 Ro60-0213 Serotonin (5-HT) Tryptamines (e.g., 5-BT, 5-CT, bufotenin, DET, DiPT, DMT, DPT, psilocin, psilocybin, tryptamine) Vabicaserin WAY-629 WAY-161503 YM-348
Antagonists: Adatanserin Agomelatine Atypical antipsychotics (e.g., asenapine, clorotepine, clozapine, fluperlapine, iloperidone, melperone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, ziprasidone, zotepine) Captodiame CEPC Cinanserin Cyproheptadine Deramciclane Desmetramadol Dotarizine Eltoprazine Ergolines (e.g., amesergide, bromocriptine, LY-53857, LY-215,840, mesulergine, metergoline, methysergide, sergolexole) Etoperidone Fluoxetine FR-260010 Irindalone Ketanserin Ketotifen Latrepirdine (dimebolin) Medifoxamine Metitepine (methiothepin) Nefazodone Pirenperone Pizotifen Propranolol Ritanserin RS-102221 S-14671 SB-200646 SB-206553 SB-221284 SB-228357 SB-242084 SB-243213 SDZ SER-082 Tedatioxetine Tetracyclic antidepressants (e.g., amoxapine, aptazapine, esmirtazapine, maprotiline, mianserin, mirtazapine) TIK-301 Tramadol Trazodone Tricyclic antidepressants (e.g., amitriptyline, nortriptyline) Typical antipsychotics (e.g., chlorpromazine, loxapine, pimozide, pipamperone, thioridazine) Xylamidine
Unknown/unsorted: Efavirenz Ergolines (e.g., ergometrine (ergonovine), methylergometrine (methylergonovine))

5-HT₃_–7

5-HT₃

Agonists: Alcohols (e.g., butanol, ethanol (alcohol), trichloroethanol) m-CPBG Phenylbiguanide Piperazines (e.g., BZP, mCPP, quipazine) RS-56812 Serotonin (5-HT) SR-57227 SR-57227A Tryptamines (e.g., 2-Me-5-HT, 5-CT, bufotenidine (5-HTQ)) Volatiles/gases (e.g., halothane, isoflurane, toluene, trichloroethane) YM-31636
Antagonists: Alosetron Anpirtoline Arazasetron AS-8112 Atypical antipsychotics (e.g., clozapine, olanzapine, quetiapine) Azasetron Batanopride Bemesetron (MDL-72222) Bupropion Cilansetron CSP-2503 Dazopride Dolasetron Galanolactone Granisetron Hydroxybupropion Lerisetron Memantine Ondansetron Palonosetron Ramosetron Renzapride Ricasetron Tedatioxetine Tetracyclic antidepressants (e.g., amoxapine, mianserin, mirtazapine) Thujone Tropanserin Tropisetron Typical antipsychotics (e.g., loxapine) Volatiles/gases (e.g., nitrous oxide, sevoflurane, xenon) Vortioxetine Zacopride Zatosetron
Unknown/unsorted: LY-53857 Piperazines (e.g., naphthylpiperazine)

5-HT₄

Agonists: 5-MT BIMU8 Capeserod Cinitapride Cisapride CJ-033466 Dazopride Metoclopramide Minesapride Mosapride Prucalopride PRX-03140 Renzapride RS-67,333 RS-67,506 Serotonin (5-HT) Tegaserod Usmarapride Velusetrag Zacopride
Antagonists: GR-113808 GR-125487 L-Lysine Piboserod RS-39604 RS-67532 SB-203186 SB-204070

5-HT_5A

Agonists: Ergolines (e.g., 2-Br-LSD (BOL-148), ergotamine, LSD) Serotonin (5-HT) Tryptamines (e.g., 5-CT) Valerenic acid
Antagonists: Asenapine Latrepirdine (dimebolin) Metitepine (methiothepin) Ritanserin SB-699551 Unknown/unsorted: Ergolines (e.g., metergoline, methysergide) Piperazines (e.g., naphthylpiperazine)

5-HT₆

Agonists: Ergolines (e.g., dihydroergocryptine, dihydroergotamine, ergotamine, lisuride, LSD, mesulergine, metergoline, methysergide) Hypidone Serotonin (5-HT) Tryptamines (e.g., 2-Me-5-HT, 5-BT, 5-CT, 5-MT, Bufotenin, E-6801, E-6837, EMD-386088, EMDT, LY-586713, N-Me-5-HT, ST-1936, tryptamine) WAY-181187 WAY-208466
Antagonists: ABT-354 Atypical antipsychotics (e.g., aripiprazole, asenapine, clorotepine, clozapine, fluperlapine, iloperidone, olanzapine, tiospirone) AVN-101 AVN-211 AVN-322 AVN-397 BGC20-760 BVT-5182 BVT-74316 Cerlapirdine EGIS-12,233 GW-742457 Idalopirdine Ketanserin Landipirdine Latrepirdine (dimebolin) Masupirdine Metitepine (methiothepin) MS-245 PRX-07034 Ritanserin Ro 04-6790 Ro 63-0563 SB-258585 SB-271046 SB-357134 SB-399885 SB-742457 Tetracyclic antidepressants (e.g., amoxapine, mianserin) Tricyclic antidepressants (e.g., amitriptyline, clomipramine, doxepin, nortriptyline) Typical antipsychotics (e.g., chlorpromazine, loxapine)
Unknown/unsorted: Ergolines (e.g., 2-Br-LSD (BOL-148), bromocriptine, lergotrile, pergolide) Piperazines (e.g., naphthylpiperazine)

5-HT₇

Agonists: 8-OH-DPAT AS-19 Bifeprunox E-55888 Ergolines (e.g., LSD) LP-12 LP-44 LP-211 RU-24,969 Sarizotan Serotonin (5-HT) Triptans (e.g., frovatriptan) Tryptamines (e.g., 5-CT, 5-MT, bufotenin, N-Me-5-HT)
Antagonists: Atypical antipsychotics (e.g., amisulpride, aripiprazole, asenapine, brexpiprazole, clorotepine, clozapine, fluperlapine, olanzapine, risperidone, sertindole, tiospirone, ziprasidone, zotepine) Butaclamol DR-4485 EGIS-12,233 Ergolines (e.g., 2-Br-LSD (BOL-148), amesergide, bromocriptine, cabergoline, dihydroergotamine, ergotamine, LY-53857, LY-215,840, mesulergine, metergoline, methysergide, sergolexole) JNJ-18038683 Ketanserin LY-215,840 Metitepine (methiothepin) Ritanserin SB-258719 SB-258741 SB-269970 SB-656104 SB-656104A SB-691673 SLV-313 SLV-314 Spiperone SSR-181507 Tetracyclic antidepressants (e.g., amoxapine, maprotiline, mianserin, mirtazapine) Tricyclic antidepressants (e.g., amitriptyline, clomipramine, imipramine) Typical antipsychotics (e.g., acetophenazine, chlorpromazine, chlorprothixene, fluphenazine, loxapine, pimozide) Vortioxetine
Unknown/unsorted: Ergolines (e.g., lisuride, pergolide) Piperazines (e.g., naphthylpiperazine)

See also: Receptor/signaling modulators
Adrenergics
Dopaminergics
Melatonergics
Monoamine reuptake inhibitors and releasing agents
Monoamine metabolism modulators
Monoamine neurotoxins

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This page was last edited on 6 December 2023, at 01:01

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References