894231550.4 67a2β,3βh12.6 ± 1.814.921000 ± 332028.9110038.1 67b2β,3αh-13.8-11.775364.3 67c2α,3αh690 ± 37-41300 ± 5300--- 682β,3αf-6.00-4.5812226.6 69a2β,3βch31.96 ± 0.082.5811000 ± 832.8773.825.7 69b2β,3αch3-2.87-4.1628769.0 69c2α,3αch3429 ± 59-15800 ± 3740--- carboxyalkyl codex2 positionconfig8da5-htne rti-77clch2c2(3-iodo-p-anilino)β,βnme2.51—2247 rti-121 ipciti-co2priβ,βnme0.4366.8285 rti-153i-co2priβ,βnh1.063.59132 rti-191i-co2prcycβ,βnme0.6115.5102 rti-114cl-co2priβ,βnme1.401,404778 rti-278no2-co2priβ,βnme8.142,1474,095 rti-190cl-co2prcycβ,βnme0.96168235 rti-193me-co2prcycβ,βnme1.681,066644 rti-117me-co2priβ,βnme6.456,0901,926 rti-150me-co2bucycβ,βnme3.742,0204,738 rti-127me-co2c(h)et2β,βnme1945003444 rti-338ethyl-co2c2phβ,βnme11047.413366 use of a cyclopropyl ester appears to enable better mat retention than does the choice of isopropyl ester. use of a cycbu resulted in greater dat selectivity than did the cycpr homologue. esters (2-alkyl) 2β-alkyl ester phenyltropanes structure short name(s. singh) 2β=r ki (nm)datwin 35428 ic50 (nm)da uptake selectivityuptake/binding 59ach=chco2ch322 ± 2123 ± 655.6 59bch2ch2co2ch323 ± 2166 ± 687.2 59c(ch2)2ch=chco2ch320 ± 2203 ± 7710.1 59d(ch22)4co2ch330 ± 2130 ± 74.3 59ech=chch2oh26 ± 3159 ± 436.1 59fch2ch2ch2oh11 ± 164 ± 325.8 59gch2ch2coc6h528 ± 247 ± 151.7 ethers (2-alkyl) see the n-desmethyl paroxetine homologues 2-alkyl ether phenyltropanes molecular structure short name(s. singh) stereochemistry datwin 35428 ic50 (nm) 5-httparoxetine ic50 (nm) netnisoxetine ic50 (nm) selectivity5-htt/dat selectivitynet/dat paroxetine623 ± 250.28 ± 0.02535 ± 150.00040.8 r-60a2β,3β308 ± 20294 ± 185300 ± 4500.917.2 r-60b2α,3β172 ± 8.852.9 ± 3.626600 ± 12000.3155 r-60c2β,3α3.01 ± 0.242.2 ± 16123 ± 9.514.140.9 s-60d2β,3β1050 ± 4588.1 ± 2.827600 ± 11000.0826.3 s-60e2α,3β1500 ± 74447 ± 472916 ± 19500.31.9 s-60f2β,3α298 ± 17178 ± 1312400 ± 7200.641.6 carboxamides u.s. patent 5,736,123 structure code(s. singh #)x2 positionconfig8dawin 35428 (ic50 nm)nenisoxetine5-htparoxetine (ic50 nm)selectivity5-htt/datselectivitynet/dat rti-10627bclcon(h)meβ,βnme12.4 ± 1.171584 ± 621313 ± 46106128 rti-11827aclconh2β,βnme11.5 ± 1.64270 ± 3591621 ± 110141371 rti-22229dmemorpholinylβ,βnme11.7 ± 0.8723601 ± 1156>100k>85472017 rti-12927eclconme2β,βnme1.38 ± 0.1942 ± 481079 ± 102792683 rti-14627dclconhch2ohβ,βnme2.05 ± 0.23144 ± 397.8 ± 1047.770.2 rti-14727iclcon(ch2)4β,βnme1.38 ± 0.033,950 ± 7212400 ± 120789852862 rti-156clcon(ch2)5β,βnme6.6158323468 rti-170clcon(h)ch2c≡chβ,βnme16.518394827 rti-172clcon(h)nh2β,βnme44.139143815 rti-174clconhcomeβ,βnme158>43k>125k rti-182clconhch2cophβ,βnme7.791722827 rti-183✲27 gclcon(ome)meβ,βnme0.85 ± 0.06549 ± 18.5724 ± 94852646 rti-18629cmecon(ome)meβ,βnme2.55 ± 0.43422 ± 263402 ± 3531334165 rti-19827hclcon(ch2)3β,βnme6.57 ± 0.67990 ± 4.8814 ± 57124151 rti-19627cclconhomeβ,βnme10.7 ± 1.259907 ± 63243700 ± 19604084926 rti-201clconhnhcophβ,βnme91.8>20k>48k rti-20827jclcono(ch2)3β,βnme1.47 ± 0.131083 ± 762470 ± 561680737 rti-21427lclcon(-ch2ch2-)2oβ,βnme2.90 ± 0.38545 ± 20688769 ± 1855306102946 rti-21527fclconet2β,βnme5.48 ± 0.195532 ± 2999433 ± 77017211009 rti-217clconh(m-c6h4oh)β,βnme4.78>30k>16k rti-218✲clcon(me)omeβ,βnme1.195201911 rti-22627 mclconmephβ,βnme45.5 ± 32202 ± 49523610 ± 212851948.4 rti-227icono(ch2)3β,βnme0.75446230 rti-22928aicon(ch2)4β,βnme0.37 ± 0.04991 ± 211728 ± 3946702678 27k6.95 ± 1.211752 ± 2023470 ± 226499252 28b1.08 ± 0.15103 ± 6.273.9 ± 8.168.495.4 28c0.75 ± 0.02357 ± 42130 ± 15.8173476 29a41.8 ± 2.454398 ± 2716371 ± 374152105 29b24.7 ± 1.936222 ± 72933928 ± 21921374252 ✲rti-183 and rti-218 suggest possible copy-error, seeing as "con(ome)me" & "con(me)ome" difference between methyl & methoxy render as the same. 2β-carboxamide-3β-phenyltropanes compound short name(s. singh) r x ic50 (nm)datwin 35428 ic50 (nm)5-httparoxetine ic50 (nm)netnisoxetine selectivity5-htt/dat selectivitynet/dat 29anh2ch341.8 ± 2.456371 ± 3744398 ± 271152105 29bn(ch2ch3)2ch324.7 ± 1.9333928 ± 21926222 ± 7291374252 29crti-186n(och3)ch3ch32.55 ± 0.433402 ± 353422 ± 261334165 29drti-2224-morpholinech311.7 ± 0.87>10000023601 ± 1156>85472017 carboxamide linked phenyltropanes dimers dimers of phenyltropanes, connected in their dual form using the c2 locant as altered toward a carboxamide structural configuring (in contrast and away from the usual inherent ecgonine carbmethoxy), as per frank ivy carroll's patent inclusive of such chemical compounds, possibly so patented due to being actively delayed pro-drugs in vivo. heterocycles these heterocycles are sometimes referred to as the "bioisosteric equivalent" of the simpler esters from which they are derived. a potential disadvantage of leaving the ββ-ester unreacted is that in addition to being hydrolyzable, it can also epimerize to the energetically more favorable trans configuration. this can happen to cocaine also. atomic positions a—c(compound model 34) several of the oxadiazoles contain the same number and types of heteroatoms, while their respective binding potencies display 8×-15× difference. a finding that would not be accounted for by their affinity originating from hydrogen bonding. to explore the possibility of electrostatic interactions, the use of molecular electrostatic potentials (mep) were employed with model compound 34 (replacing the phenyltropane moiety with a methyl group). focusing on the vicinity of the atoms @ positions a—c, the minima of electrostatic potential near atom position a (δvmin(a)), calculated with semi-empirical (am1) quantum mechanics computations (superimposing the heterocyclic and phenyl rings to ascertain the least in the way of steric and conformational discrepancies) found a correlation between affinity @ dat and δvmin(a): wherein the values for the latter for 32c = 0, 32g = -4, 32h = -50 & 32i = -63 kcal/mol. in contrast to this trend, it is understood that an increasingly negative δvmin is correlated with an increase of strength in hydrogen bonding, which is the opposing trend for the above; this indicates that the 2β-substituents (at least for the heterocyclic class) are dominated by electrostatic factors for binding in-the-stead of the presumptive hydrogen bonding model for this substituent of the cocaine-like binding ligand. 3-substituted-isoxazol-5-yl n-methylphenyltropanes with 1r β,β stereochemistry. code(s.s. #) x r da ne 5ht rti-165cl3-methylisoxazol-5-yl0.59181572 rti-171me3-methylisoxazol-5-yl0.932543818 rti-180i3-methylisoxazol-5-yl0.7367.936.4 rti-177 β-cppit32gcl3-phenylisoxazol-5-yl1.28 ± 0.18504 ± 292420 ± 136 rti-176me3-phenylisoxazol-5-yl1.583985110 rti-181i3-phenylisoxazol-5-yl2.57868100 rti-184hmethyl43.3—6208 rti-185hph285—>12k rti-334cl3-ethylisoxazol-5-yl0.501203086 rti-335clisopropyl1.199542318 rti-336cl3-(4-methylphenyl)isoxazol-5-yl4.0917145741 rti-337cl3-t-butyl-isoxazol-5-yl7.31632137k rti-345clp-chlorophenyl6.425290>76k rti-346clp-anisyl1.577625880 rti-347clp-fluorophenyl1.869187257 rti-354me3-ethylisoxazol-5-yl1.622996400 rti-366mer = isopropyl4.52523 (1550)42,900 (3900) rti-371mep-chlorophenyl8.74>100k (60,200)>100k (9090) rti-386mep-anisyl3.93756 (450)4027 (380) rti-387mep-fluorophenyl6.45917 (546)>100k (9400) 3-substituted-1,2,4-oxadiazole heterocyclic (n-methyl)phenyltropanes with 1r stereochemistry. structure code(singh's #) x r dat (ic50 nm)displacement of win 35428 net (ic50 nm)nisoxetine 5-htt (ic50 nm)paroxetine selectivity5-htt/dat selectivitynet/dat ααrti-87h3-methyl-1,2,4-oxadiazole20436k30k βαrti-119h3-methyl-1,2,4-oxadiazole1677k41k αβrti-124h3-methyl-1,2,4-oxadiazole102871k33k rti-125(32a)cl3-methyl-1,2,4-oxadiazole4.05 ± 0.57363 ± 362584 ± 80063789.6 ββrti-126(31)h3-methyl-1,2,4-oxadiazole100 ± 67876 ± 5513824 ± 42038.3788 rti-130(32c)cl3-phenyl-1,2,4-oxadiazole1.62 ± 0.02245 ± 13195 ± 5120151 rti-141 (32d)cl3-(p-anisyl)-1,2,4-oxadiazole1.81 ± 0.19835 ± 8337 ± 40186461 rti-143(32e)cl3-(p-chlorophenyl)-1,2,4-oxadiazole4.06 ± 0.2240270 ± 180(4069)404 ± 5699.59919 rti-144 (32f)cl3-(p-bromophenyl)-1,2,4-oxadiazole3.44 ± 0.361825 ± 170106 ± 1030.8532 βrti-151 (33)me3-phenyl-1,2,4-oxadiazole2.33 ± 0.2660 ± 21074 ± 13045925.7 αrti-152me3-phenyl-1,2,4-oxadiazole494—1995 rti-154(32b)cl3-isopropyl-1,2,4-oxadiazole6.00 ± 0.55135 ± 133460 ± 25057722.5 rti-155cl3-cyclopropyl-1,2,4-oxadiazole3.411774362 rti-4229-470 structure. highly excited 94 pm dat signal.↑ above: 2d skeletal depiction.↓ below: 3d tube model. n-methylphenyltropanes with 1r β,β stereochemistry. structure code x 2 group dat (ic50 nm)displacement of win 35428 net (ic50 nm)displacement of nisoxetine 5-htt (ic50 nm)displacement of paroxetine selectivity5-htt/dat selectivitynet/dat rti-157metetrazole1557>37k>43k rti-163cltetrazole911—5456 rti-178me5-phenyl-oxazol-2-yl35.46771699 rti-188cl5-phenyl-1,3,4-oxadiazol-2-yl12.69303304 rti-189(32i)cl5-phenyl-oxazol-2-yl19.7 ± 1.98496 ± 421120 ± 10756.825.5 rti-194me5-methyl-1,3,4-oxadiazol-2-yl4.452534885 rti-195me5-phenyl-1,3,4-oxadiazol-2-yl47.51310>22,000 rti-199me5-phenyl-1,3,4-thiadiazol-2-yl35.9>24,000>51,000 rti-200cl5-phenyl-1,3,4-thiadiazol-2-yl15.34142>18,000 rti-202clbenzothiazol-2-yl1.374031119 rti-219cl5-phenylthiazol-2-yl5.71851610,342 rti-262cl188.2 ± 5.01595.25 ± 57385207 ± 48831628 rti-370me3-(p-cresyl)isoxazol-5-yl8.746980>100k rti-371cl3-(p-chlorophenyl)isoxazol-5-yl13>100k>100k rti-436me-ch=chph3.091960 (1181)335 (31) rti-470clo-cl-benzothiazol-2-yl0.0941590 (994)1080 (98) rti-451mebenzothiazol-2-yl1.53476 (287)7120 (647) 32g1.28 ± 0.18504 ± 292420 ± 1361891394 32h12.6 ± 10.3929 ± 88330 ± 19626273.7 above is taken from: rti, kuhar, et al. u.s. patent 5,935,953 (1999). n.b there are some alternative ways of making the tetrazole ring however; c.f. the sartan drugs synthesis schemes. bu3snn3 is a milder choice of reagent than hydrogen azide (c.f. irbesartan). acyl (c2-propanoyl) indolylcf. the tamagnan series of phenyltropanes for examples with a methylene unit spacer breaking up the indole. #(#)xy2 positionconfig8da5-htne wf-23(39n)β-naphthylc(o)etβ,βnme0.1150.394no data wf-31 pit-prihc.o.etβ,βnme61554.5no data wf-11✲ ptt(39e)meh-c.o.etβ,βnme8.2131no data wf-25(39a)hh-c.o.etβ,βnme48.31005no data wf-336-meobnc(o)etα,βnme0.132.24no data ✲compound wf-11 has been shown, under consistent exposure, to elicit a biological response opposite of cocaine i.e. tyrosine hydroxylase gene expression down-regulation (instead of up-regulation as has been observed to be the case for chronic cocaine administration) 2β-acyl-3β-phenyltropane structures structure s. singh'salphanumericassignation(name) r1 r2 dat rti-55 ic50 (nm) 5-htt paroxetine ki (nm) selectivity 5-htt/dat cocaine173 ± 19—— troparil11a(win 35065-2)98.8 ± 12.2—— wf-2539ac2h5c6h548.3 ± 2.81005 ± 11220.8 39bch3c6h5114 ± 221364 ± 61612.0 39cc2h5c6h4-4-f15.3 ± 2.8630 ± 6741.2 39dch3c6h4-4-f70.8 ± 13857 ± 18712.1 wf-1139ec2h5c6h4-4-ch38.2 ± 1.6131 ± 116.0 (+)-39ec2h5c6h4-4-ch34.21 ± 0.0574 ± 1217.6 (-)-39ec2h5c6h4-4-ch31337 ± 122>10000— 39fch3c6h4-4-ch39.8 ± 0.5122 ± 2212.4 39gch3c6h4-4-c2h5152 ± 2478.2 ± 220.5 39hc2h5c6h4-4-ch(ch3)2436 ± 4135.8 ± 4.40.08 39ic2h5c6h4-4-c(ch3)32120 ± 6301771 ± 4740.8 39jc2h5c6h4-4-c6h52.29 ± 1.084.31 ± 0.011.9 39kc2h5c6h4-2-ch31287 ± 322710000>7.8 39lc2h51-naphthyl5.43 ± 1.2720.9 ± 2.93.8 39mch31-naphthyl10.1 ± 2.225.6 ± 5.12.5 wf-2339nc2h52-naphthyl0.115 ± 0.0210.394 ± 0.0743.5 39och32-naphthyl0.28 ± 0.111.06 ± 0.363.8 39pc2h5c6h4-4-ch(c2h5)2270 ± 38540 ± 512.0 39qc2h5c6h4-4-c6h11320 ± 5597 ± 120.30 39rc2h5c6h4-4-ch=ch20.90 ± 0.343.2 ± 1.33.5 39sc2h5c6h4-4-c(=ch2)ch37.2 ± 2.10.82 ± 0.380.1 2β-acyl-3β-naphthyl substituted 2β-acyl-3β-(substituted naphthyl)-8-azabicyclooctanes structure short assignation(numeric code, davies ub)s. singh r datrti-55ɑic50 nm sertparoxetinebki nm netnisoxetinecki nm potency ratiosert/dat potency ratiosert/net wf-11(6)4′-me8.2 ± 1.6131 ± 1065 ± 9.20.060.5 wf-31(7)4′-ipr436 ± 4136 ± 4>10,00012>250 wf-23(8)2-naphthalene0.12 ± 0.020.39 ± 0.072.9 ± 0.50.37 2β-acyl-3β-1-naphthalene(9a)4′-h5.3 ± 1.321 ± 2.949 ± 100.318 (9b)4′-me25.1 ± 0.58.99 ± 1.70163 ± 36318 (9c)4′-et75.1 ± 11.9175 ± 254769 ± 6880.727 (9d)4′-ipr225 ± 36136 ± 64>10,0002>73.5 (10a)6′-et0.15 ± 0.040.38 ± 0.1927.7 ± 9.60.474 (10b)6′-ipr0.39 ± 0.041.97 ± 0.33no data0.2— (10ce)6′- ome0.13 ± 0.042.24 ± 0.34no data0.05— (10d)5′-et, 6′-ome30.8 ± 6.67.55 ± 1.573362 ± 1484.1445 (10e)5′-c(me)=ch2, 6′-ome45.0 ± 3.788.0 ± 13.32334 ± 3780.526.5 (10f)6′-i0.35 ± 0.070.37 ± 0.02no data1.0— (10g)7′-i0.45 ± 0.050.47 ± 0.02no data0.5d— (10h)5′-no2, 6′-ome148 ± 5015 ± 1.6no data10— (10i)5′-i, 6′-ome1.31 ± 0.332.27 ± 0.31781 ± 1810.6344 (10j)5′-come, 6′-ome12.6 ± 3.815.8 ± 1.65498 ± 240.832 (11a)2β-coch3, 1-naphthyl10 ± 2.226 ± 5.1165 ± 400.46.3 (11b)2α-coch3, 1-naphthyl97 ± 21217 ± 55no data0.45— (11c)2α-coch2ch3, 2-naphthyl2.51 ± 0.8216.4 ± 2.068.0 ± 10.80.154.1 (11d)2β-coch3, 2-naphthyl1.27 ± 0.151.06 ± 0.364.9 ± 1.21.24.6 (11e)2β-coch(ch3)2, 2-naphthyl0.25 ± 0.082.08 ± 0.8037.6 ± 10.50.1218.1 (11f)79a2β-coch2ch3, 2-naphthyl, n8-demethyl0.03 ± 0.010.23 ± 0.072.05 ± 0.90.138.9 ɑ nonspecific binding was determined in the presence of 1.0 μm wf-23(source equates wf-23 as analogue 3a, but table gives # as analogue 8) b nonspecific binding was determined in the presence of 10.0 μm fluoxetine c nonspecific binding was determined in the presence of 1.0 μm desipramine d ratio shown as halved; a possible copy-error due to closeness to 1:1 of other indicated values e sources differ on whether c2 position acyl is alpha or beta configured ester reduction note: p-fluorophenyl is weaker than the others. rti-145 is not peroxy, it is a methyl carbonate. codex2 positionconfig8da5-htne rti-100f-ch2ohβ,βnme474741no data rti-101i-ch2ohβ,βnme2.226no data rti-99br-ch2ohβ,βnme1.4951no data rti-93cl-ch2ohβ,βnme1.5320443.8 rti-105cl-ch2oacβ,βnme1.60143127 rti-123cl-ch2obzβ,βnme1.783.53393 rti-145cl-ch2oco2meβ,βnme9.602.931.48 2-alkane/alkene 2-alkane/alkene-3-phenyltropanes structure singh's # r x datmazindol displacement da uptake 5-ht uptake selectivityda uptake/dat binding 11awin 35062-289.453.71860.6 11c0.83 ± 00.728.5 ± 0.9—34.3 11f5.766.9223.21.2 41a(ch2)2ch3h12.26.8986.80.6 41b(ch2)3c6h5h16 ± 2a43 ± 13b—2.7 42(ch2)2ch3f5.281.9921.70.4 43ach=ch2cl0.59 ± 0.152.47 ± 0.5—4.2 43be-ch=chclcl0.42 ± 0.041.13 ± 0.27—2.7 43cz-ch=chclcl0.22 ± 0.020.88 ± 0.05—4.0 43de-ch=chc6h5cl0.31 ± 0.040.66 ± 0.01—2.1 43ez-ch=chc6h5cl0.14 ± 0.070.31 ± 0.09—2.2 43fch2ch3cl2.17 ± 0.202.35 ± 0.52—1.1 43 g(ch2)2ch3cl0.94 ± 0.081.08 ± 0.05—1.1 43h(ch2)3ch3cl1.21 ± 0.180.84 ± 0.05—0.7 43i(ch2)5ch3cl156 ± 15271 ± 3—1.7 43j(ch2)2c6h5cl1.43 ± 0.031.54 ± 0.08—1.0 44a(ch2)2ch3ch31.571.1010.30.7 44b(ch2)3ch3ch31.821.3115.10.7 45(ch2)2ch3h74.930.23890.4 46(ch2)2ch3f21.112.199.60.6 47a(ch2)2ch3ch38.9111.850.11.3 47b(ch2)3ch3ch311.410.151.00.9 aki value for displacement of win 35428. bic50 value. compound 48para-hydropara-chloro irreversible covalent (cf. ionic) c2 ligands irreversible (phenylisothiocyanate) binding ligand (murthy, v.; martin, t. j.; kim, s.; davies, h. m. l.; childers, s. r. (2008). "in vivo characterization of a novel phenylisothiocyanate tropane analog at monoamine transporters in rat brain". journal of pharmacology and experimental therapeutics. 326 (2): 587–595. doi:10.1124/jpet.108.138842. pmid 18492949. s2cid 5996473.) rti-76: 4′-isothiocyanatophenyl (1r,2s,3s,5s)-3-(4-chlorophenyl)-8-methyl-8-azabicyclooctane-2-carboxylate. also known as: 3β-(p-chlorophenyl)tropan-2β-carboxylic acid p-isothiocyanatophenylmethyl ester. c2 acyl, n8 phenylisothiocyanate hd-205 (murthy et al., 2007) note the contrast to the phenylisothiocyanate covalent binding site locations as compared to the one on p-isococ, a non-phenyltropane cocaine analogue. benztropine based (c2-position hetero-substituted) phenyltropanes 2-(diarylmethoxymethyl)-3β-aryltropanes & 2β--3β-aryltropanes. structure compound r x y win 35,428@ datki (nm) citalopram@ sertki (nm) nisoxetine@ netki (nm) pirenzepine@ m1ki (nm) 9ach3hh34 ± 2121 ± 19684 ± 10010,600 ± 1,100 9bfhh49 ± 12——— 9cclhh52 ± 2.1147 ± 81,190 ± 7211,000 ± 1,290 9dch3clh80 ± 9443 ± 604,400 ± 23831,600 ± 4,300 9efclh112 ± 11——— 9fclclh76 ± 7462 ± 362,056 ± 23639,900 ± 5,050 9gch3ff62 ± 7233 ± 241,830 ± 17715,500 ± 1,400 9hfff63 ± 13——— 9iclff99 ± 18245 ± 162,890 ± 22216,300 ± 1,300 10ach3hh455 ± 36530 ± 722,609 ± 19512,600 ± 1,790 10cclhh478 ± 72408 ± 163,998 ± 25611,500 ± 1,720 10dch3clh937 ± 841,001 ± 10922,500 ± 2,82118,200 ± 2,600 10fclclh553 ± 1061,293 ± 405,600 ± 1839,600 ± 600 10gch3ff690 ± 76786 ± 6716,000 ± 6379,700 ± 900 10iclff250 ± 40724 ± 10052,300 ± 13,6009,930 ± 1,090 12ahhh139 ± 1561 ± 9207 ± 307,970 ± 631 12bhclh261 ± 1945 ± 3—24,600 ± 2,930 12chff60 ± 7——— f&b series (biotin side-chains etc.) one patent claims a series of compounds with biotin-related sidechains are pesticides. images of the biotin c2 side-chained phenyltropanes, click to structurecodepara-xc2-tropane positionconfigdane5-ht —hf1β,β——— rti-224mef1cβ,β4.49—155.6 rti-233mef2β,β4.3851673.6 rti-235mef3dβ,β1.7540272.4 ——f3β,β——— rti-236meb1dβ,β1.6386.8138 rti-237meb2dβ,β7.27258363 rti-244meb3dβ,β15.6180933.7 rti-245clf4cβ,β77.3—— rti-246mef4cβ,β50.33000— ——f5β,β——— rti-248clf6cβ,β9.7346746.96 rti-249clf1cβ,β8.32502381.6 rti-266mef2β,β4.80836842 rti-267mef7 wrongβ,β2.52324455 rti-268mef7 rightβ,β3.891014382 rti-269mef8β,β5.55788986 miscellany (i.e. misc./miscellaneous) c2-substituents structurecodex2 positionconfig8da5-htne rti-102ico2hβ,βnme474192843,400 rti-103brco2hβ,βnme278307017,400 rti-104fco2hβ,βnme2744>100k>100k rti-108cl-ch2clβ,βnme2.6498129.8 rti-241me-ch2co2meβ,βnme1.02619124 rti-139cl-ch3β,βnme1.678557 rti-161cl-c≡nβ,βnme13.118872516 rti-230clh3c–c=ch2β,βnme1.2857141 rti-240cl-chme2β,βnme1.3838.484.5 rti-145cl-ch2oco2meβ,βnme9.602,9321,478 rti-158me-c≡nβ,βnme5750951624 rti-131me-ch2nh2β,βnme10.5855120 rti-164me-ch2nhmeβ,βnme13.62246280 rti-132me-ch2nme2β,βnme3.48206137 rti-239me-chme2β,βnme0.6111435.6 rti-338et-co2ch2phβ,βnme11047.413366 rti-348h-phβ,βnme28.2>34,0002670 c2-truncated/descarboxyl (non-ecgonine w/o 2-position-replacement tropanes) aryl-tropenes wo 2004113297, peters, dan; olsen, gunnar m. & nielsen, elsebet oestergaard et al., "aza-ring derivatives and their use as monoamine neurotransmitter re-uptake inhibitors", published 2004-12-29, assigned to neurosearch as test compoundda-uptake ic50(μm)na-uptake ic50(μm)5-ht-uptake ic50(μm) (+)-3-(4-chlorophenyl)-8-h-aza-bicyclooct-2-ene0.260.0280.010 (+)-3-napthalen-2-yl-8-azabicyclooct-2-ene0.0580.0130.00034 (–)-8-methyl-3-(naphthalen-2-yl)-8-azabicylooct-2-ene0.0340.0180.00023 us 0 8-azabicyclooct-2-ene derivatives test compound da uptake ic50(μm) ne uptake ic50(μm) 5-ht uptake ic50(μm) (±)-3-(3,4-dichlorophenyl)-8-methyl-8-azabicyclooct-2-ene0.0790.0260.0047 u.s. patent 2,001,047,028 test compound da uptake ic50(μm) ne uptake ic50(μm) 5-ht uptake ic50(μm) (±)-3-(4-cyanophenyl)-8-methyl-8-azabicyclooct-2-ene184.90.047 (±)-3-(4-nitrophenyl)-8-methyl-8-azabicyclooct-2-ene1.50.50.016 (±)-3-(4-trifluoromethoxyphenyl)-8-methyl-8-azabicyclooct-2-ene22.008.000.0036 enantioselective nonstandard configurations (non-2β-,3β-) β,α stereochemistry structure compound(rti #)(s. singh's #)x2 groupconfig8dat ic50 (nm)win 354285-htt ic50 (nm)paroxetinenet ic50 (nm)nisoxetineselectivity5-htt/datselectivitynet/dat rti-14020ahco2meβ,αnme101 ± 165,701 ± 7212,076 ± 28556.420.6 rti-352ɑ20dico2meβ,αnme2.86 ± 0.1664.9 ± 1.9752.4 ± 4.922.818.4 rti-549brco2meβ,αnme————— rti-319b3α-2-naphthylco2meβ,αnme1.1 ± 0.0911.4 ± 1.370.2 ± 6.28—— rti-286c20bfco2meβ,αnme21 ± 0.575062