# Electronic Supplementary Material (ESI) for Medicinal Chemistry Communications # This journal is © The Royal Society of Chemistry 2012 data_global #TrackingRef '- C1MD00217A_ccdc_819449_cif.txt' _journal_name_full MedChemComm _journal_coden_cambridge 1476 _journal_year ? _journal_volume ? _journal_page_first ? loop_ _publ_author_name _publ_author_address C.Lecoutey ; University of Caen Basse-Normandie, U.F.R. des Sciences Pharmaceutiques, Centre d'\'Etudes et de Recherche sur le M\'edicament de Normandie, UPRES EA-4258, FR CNRS INC3M, Boulevard Becquerel, 14032 Caen Cedex, France ; C.Rochais ; University of Caen Basse-Normandie, U.F.R. des Sciences Pharmaceutiques, Centre d'\'Etudes et de Recherche sur le M\'edicament de Normandie, UPRES EA-4258, FR CNRS INC3M, Boulevard Becquerel, 14032 Caen Cedex, France ; S.Butt-Guelle ; University of Caen Basse-Normandie, U.F.R. des Sciences Pharmaceutiques, Centre d'\'Etudes et de Recherche sur le M\'edicament de Normandie, UPRES EA-4258, FR CNRS INC3M, Boulevard Becquerel, 14032 Caen Cedex, France ; S.Corvaisier ; University of Caen Basse-Normandie, U.F.R. des Sciences Pharmaceutiques, Centre d'\'Etudes et de Recherche sur le M\'edicament de Normandie, UPRES EA-4258, FR CNRS INC3M, Boulevard Becquerel, 14032 Caen Cedex, France ; F.Dulin ; University of Caen Basse-Normandie, U.F.R. des Sciences Pharmaceutiques, Centre d'\'Etudes et de Recherche sur le M\'edicament de Normandie, UPRES EA-4258, FR CNRS INC3M, Boulevard Becquerel, 14032 Caen Cedex, France ; ; A.Lepailleur ; ; University of Caen Basse-Normandie, U.F.R. des Sciences Pharmaceutiques, Centre d'\'Etudes et de Recherche sur le M\'edicament de Normandie, UPRES EA-4258, FR CNRS INC3M, Boulevard Becquerel, 14032 Caen Cedex, France ; 'J.Sopkova-de Oliveira Santos' ; University of Caen Basse-Normandie, U.F.R. des Sciences Pharmaceutiques, Centre d'\'Etudes et de Recherche sur le M\'edicament de Normandie, UPRES EA-4258, FR CNRS INC3M, Boulevard Becquerel, 14032 Caen Cedex, France ; S.Rault ; University of Caen Basse-Normandie, U.F.R. des Sciences Pharmaceutiques, Centre d'\'Etudes et de Recherche sur le M\'edicament de Normandie, UPRES EA-4258, FR CNRS INC3M, Boulevard Becquerel, 14032 Caen Cedex, France ; P.Dallemagne ; University of Caen Basse-Normandie, U.F.R. des Sciences Pharmaceutiques, Centre d'\'Etudes et de Recherche sur le M\'edicament de Normandie, UPRES EA-4258, FR CNRS INC3M, Boulevard Becquerel, 14032 Caen Cedex, France ; _publ_contact_author_address ; University of Caen Basse-Normandie, U.F.R. des Sciences Pharmaceutiques, Centre d'\'Etudes et de Recherche sur le M\'edicament de Normandie, UPRES EA-4258, FR CNRS INC3M, Boulevard Becquerel, 14032 Caen Cedex, France ; _publ_contact_author_email patrick.dallemagne@unicaen.fr _publ_contact_author_fax '332 31 56 68 03' _publ_contact_author_phone '332 31 56 68 13' _publ_contact_author_name 'Dallemagne, Patrick' _publ_section_title ; Dual AChE/5-HT4 Receptors Multi-Target Directed Ligands with Potential Therapeutic Interest in Alzheimer Disease Treatment. ; data_cc5j #TrackingRef '- C1MD00217A_ccdc_819449_cif.txt' _database_code_depnum_ccdc_archive 'CCDC 819449' #TrackingRef '4870_web_deposit_cif_file_0_J #anaSopkova-deOliveiraSantos_1301476918.cif' _audit_creation_method SHELXL-97 _chemical_name_systematic ; 5-[(1-(4-methoxybenzyl)piperidin-4-yl)methyloxy]pyrrolo [1,2-a]thieno[3,2-e]pyrazine ; _chemical_name_common ; 5-((1-(4-methoxybenzyl)piperidin-4-yl)methyloxy)pyrrolo (1,2- a)thieno(3,2-e)pyrazine ; _chemical_melting_point 421 _chemical_formula_moiety 'C23 H25 N3 O2 S' _chemical_formula_sum 'C23 H25 N3 O2 S' _chemical_formula_weight 407.52 _chemical_compound_source synthetised loop_ _atom_type_symbol _atom_type_description _atom_type_scat_dispersion_real _atom_type_scat_dispersion_imag _atom_type_scat_source C C 0.0033 0.0016 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' H H 0.0000 0.0000 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' N N 0.0061 0.0033 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' O O 0.0106 0.0060 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' S S 0.1246 0.1234 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' _symmetry_cell_setting Monoclinic _symmetry_space_group_name_H-M 'P2(1)/c ' _symmetry_space_group_name_Hall '-P 2ybc' loop_ _symmetry_equiv_pos_as_xyz 'x, y, z' '-x, y+1/2, -z+1/2' '-x, -y, -z' 'x, -y-1/2, z-1/2' _cell_length_a 18.4455(5) _cell_length_b 5.8641(2) _cell_length_c 20.5004(6) _cell_angle_alpha 90.00 _cell_angle_beta 114.0670(10) _cell_angle_gamma 90.00 _cell_volume 2024.69(11) _cell_formula_units_Z 4 _cell_measurement_temperature 150(2) _cell_measurement_reflns_used 9969 _cell_measurement_theta_min 2.42 _cell_measurement_theta_max 33.07 _exptl_crystal_description prism _exptl_crystal_colour 'translucent light orange' _exptl_crystal_size_max 0.370 _exptl_crystal_size_mid 0.240 _exptl_crystal_size_min 0.110 _exptl_crystal_density_meas ? _exptl_crystal_density_diffrn 1.337 _exptl_crystal_density_method 'not measured' _exptl_crystal_F_000 864 _exptl_absorpt_coefficient_mu 0.185 _exptl_absorpt_correction_type multi-scan _exptl_absorpt_correction_T_min 0.6543 _exptl_absorpt_correction_T_max 0.7465 _exptl_absorpt_process_details 'APEX2 software' _exptl_special_details ; ? ; _diffrn_ambient_temperature 150(2) _diffrn_radiation_wavelength 0.71073 _diffrn_radiation_type MoK\a _diffrn_radiation_source 'fine-focus sealed tube' _diffrn_radiation_monochromator graphite _diffrn_measurement_device_type 'CCD area detector' _diffrn_measurement_method 'phi and omega scans' _diffrn_detector_area_resol_mean ? _diffrn_standards_number ? _diffrn_standards_interval_count ? _diffrn_standards_interval_time ? _diffrn_standards_decay_% 0 _diffrn_reflns_number 57859 _diffrn_reflns_av_R_equivalents 0.0408 _diffrn_reflns_av_sigmaI/netI 0.0374 _diffrn_reflns_limit_h_min -28 _diffrn_reflns_limit_h_max 28 _diffrn_reflns_limit_k_min -8 _diffrn_reflns_limit_k_max 9 _diffrn_reflns_limit_l_min -31 _diffrn_reflns_limit_l_max 31 _diffrn_reflns_theta_min 2.18 _diffrn_reflns_theta_max 33.18 _reflns_number_total 7719 _reflns_number_gt 5728 _reflns_threshold_expression >2sigma(I) _computing_data_collection 'APEX2 software' _computing_cell_refinement 'APEX2 software' _computing_data_reduction 'BRUKER SAINT' _computing_structure_solution 'BRUKER SHELXTL (Sheldrick, 1990)' _computing_structure_refinement 'SHELXL-97 (Sheldrick, 1997)' _computing_molecular_graphics 'ORTEP-3 (Farrugia, 1997)' _computing_publication_material 'SHELXL-97 (Sheldrick, 1997)' _refine_special_details ; Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ > 2sigma(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ; _refine_ls_structure_factor_coef Fsqd _refine_ls_matrix_type full _refine_ls_weighting_scheme calc _refine_ls_weighting_details 'calc w=1/[\s^2^(Fo^2^)+(0.0463P)^2^+0.7332P] where P=(Fo^2^+2Fc^2^)/3' _atom_sites_solution_primary direct _atom_sites_solution_secondary difmap _atom_sites_solution_hydrogens difmap _refine_ls_hydrogen_treatment refall _refine_ls_extinction_method none _refine_ls_extinction_coef ? _refine_ls_number_reflns 7719 _refine_ls_number_parameters 362 _refine_ls_number_restraints 0 _refine_ls_R_factor_all 0.0636 _refine_ls_R_factor_gt 0.0404 _refine_ls_wR_factor_ref 0.1074 _refine_ls_wR_factor_gt 0.0947 _refine_ls_goodness_of_fit_ref 1.018 _refine_ls_restrained_S_all 1.018 _refine_ls_shift/su_max 0.001 _refine_ls_shift/su_mean 0.000 loop_ _atom_site_label _atom_site_type_symbol _atom_site_fract_x _atom_site_fract_y _atom_site_fract_z _atom_site_U_iso_or_equiv _atom_site_adp_type _atom_site_occupancy _atom_site_symmetry_multiplicity _atom_site_calc_flag _atom_site_refinement_flags _atom_site_disorder_assembly _atom_site_disorder_group S1 S 1.085971(17) 1.12701(5) 1.134070(16) 0.02011(7) Uani 1 1 d . . . O1 O 0.81836(4) 0.53860(13) 1.08427(4) 0.01683(15) Uani 1 1 d . . . N4 N 0.95392(5) 1.00547(14) 1.15783(5) 0.01380(16) Uani 1 1 d . . . N3 N 0.93128(5) 0.62591(15) 1.06678(5) 0.01603(17) Uani 1 1 d . . . N2 N 0.56206(5) 0.19744(15) 0.90153(5) 0.01650(18) Uani 1 1 d . . . C5 C 0.89078(6) 0.85470(17) 1.14488(6) 0.01449(19) Uani 1 1 d . . . C6 C 1.00530(6) 0.96480(17) 1.12566(6) 0.01497(19) Uani 1 1 d . . . C7 C 0.80419(6) 0.35417(17) 1.03383(6) 0.01609(19) Uani 1 1 d . . . C8 C 0.57518(6) 0.37167(18) 0.95645(6) 0.0177(2) Uani 1 1 d . . . C32 C 0.72063(6) 0.26720(17) 1.01537(6) 0.01554(19) Uani 1 1 d . . . C10 C 0.61400(7) 0.00233(18) 0.93329(6) 0.0186(2) Uani 1 1 d . . . C11 C 0.70153(6) 0.06968(17) 0.96207(6) 0.0174(2) Uani 1 1 d . . . C12 C 0.47899(7) 0.12179(19) 0.86994(7) 0.0206(2) Uani 1 1 d . . . O2 O 0.26427(6) 0.84379(17) 0.73684(5) 0.0320(2) Uani 1 1 d . . . C14 C 0.88828(7) 1.12885(19) 1.22058(6) 0.0187(2) Uani 1 1 d . . . C15 C 0.66005(6) 0.45816(17) 0.98361(6) 0.0167(2) Uani 1 1 d . . . C16 C 0.88313(6) 0.66904(17) 1.09701(6) 0.01458(19) Uani 1 1 d . . . C17 C 0.42227(6) 0.31157(19) 0.83206(6) 0.0184(2) Uani 1 1 d . . . C18 C 1.05418(7) 0.76446(19) 1.05491(6) 0.0199(2) Uani 1 1 d . . . C19 C 0.95201(6) 1.17260(18) 1.20357(6) 0.0166(2) Uani 1 1 d . . . C20 C 0.99422(6) 0.77746(17) 1.08220(6) 0.01582(19) Uani 1 1 d . . . C21 C 0.84947(6) 0.93090(19) 1.18393(6) 0.0172(2) Uani 1 1 d . . . C22 C 0.35651(7) 0.3559(2) 0.84723(6) 0.0220(2) Uani 1 1 d . . . C23 C 0.43294(7) 0.4470(2) 0.78084(7) 0.0207(2) Uani 1 1 d . . . C24 C 0.38102(7) 0.6244(2) 0.74645(6) 0.0196(2) Uani 1 1 d . . . C25 C 0.31733(7) 0.6694(2) 0.76451(6) 0.0213(2) Uani 1 1 d . . . C26 C 0.27505(9) 0.9944(2) 0.68768(8) 0.0280(3) Uani 1 1 d . . . C27 C 0.30451(7) 0.5317(2) 0.81421(7) 0.0254(3) Uani 1 1 d . . . C28 C 1.10654(7) 0.9398(2) 1.07837(7) 0.0228(2) Uani 1 1 d . . . H14 H 0.5637(8) 0.309(2) 0.9979(7) 0.020(3) Uiso 1 1 d . . . H9 H 0.7171(8) 0.211(2) 1.0605(7) 0.020(3) Uiso 1 1 d . . . H5 H 0.8087(8) 0.411(2) 0.9904(7) 0.019(3) Uiso 1 1 d . . . H8 H 0.6686(8) 0.578(2) 1.0191(7) 0.018(3) Uiso 1 1 d . . . H3 H 0.9905(8) 1.288(2) 1.2183(7) 0.020(3) Uiso 1 1 d . . . H11 H 0.7143(8) 0.114(2) 0.9212(7) 0.020(3) Uiso 1 1 d . . . H15 H 0.4767(8) 0.001(3) 0.8364(8) 0.025(4) Uiso 1 1 d . . . H12 H 0.6029(8) -0.115(2) 0.8957(8) 0.022(4) Uiso 1 1 d . . . H1 H 0.8033(9) 0.859(2) 1.1857(8) 0.022(4) Uiso 1 1 d . . . H6 H 0.8449(8) 0.237(2) 1.0555(7) 0.018(3) Uiso 1 1 d . . . H7 H 0.6689(8) 0.529(2) 0.9433(7) 0.019(3) Uiso 1 1 d . . . H13 H 0.5367(8) 0.496(2) 0.9343(8) 0.021(3) Uiso 1 1 d . . . H10 H 0.7348(9) -0.064(3) 0.9846(8) 0.025(4) Uiso 1 1 d . . . H4 H 1.0564(9) 0.649(3) 1.0225(8) 0.027(4) Uiso 1 1 d . . . H2 H 0.8727(9) 1.220(3) 1.2518(8) 0.025(4) Uiso 1 1 d . . . H16 H 0.6010(8) -0.065(2) 0.9743(7) 0.020(3) Uiso 1 1 d . . . H19 H 0.3916(9) 0.713(3) 0.7106(8) 0.025(4) Uiso 1 1 d . . . H20 H 0.3475(9) 0.261(3) 0.8825(8) 0.025(4) Uiso 1 1 d . . . H17 H 0.4633(9) 0.055(3) 0.9070(8) 0.027(4) Uiso 1 1 d . . . H18 H 0.4770(9) 0.414(3) 0.7694(8) 0.028(4) Uiso 1 1 d . . . H23 H 0.2696(10) 0.914(3) 0.6426(9) 0.041(5) Uiso 1 1 d . . . H22 H 0.2589(10) 0.564(3) 0.8248(9) 0.038(4) Uiso 1 1 d . . . H21 H 1.1523(9) 0.970(3) 1.0677(8) 0.032(4) Uiso 1 1 d . . . H25 H 0.3289(11) 1.063(3) 0.7071(9) 0.042(5) Uiso 1 1 d . . . H24 H 0.2320(11) 1.112(3) 0.6771(9) 0.044(5) Uiso 1 1 d . . . loop_ _atom_site_aniso_label _atom_site_aniso_U_11 _atom_site_aniso_U_22 _atom_site_aniso_U_33 _atom_site_aniso_U_23 _atom_site_aniso_U_13 _atom_site_aniso_U_12 S1 0.01656(13) 0.02124(12) 0.02425(15) -0.00492(10) 0.01008(11) -0.00610(9) O1 0.0144(4) 0.0184(3) 0.0170(4) -0.0034(3) 0.0057(3) -0.0044(3) N4 0.0121(4) 0.0159(3) 0.0123(4) -0.0007(3) 0.0039(3) -0.0008(3) N3 0.0142(4) 0.0173(4) 0.0160(4) -0.0018(3) 0.0054(3) -0.0019(3) N2 0.0121(4) 0.0149(4) 0.0197(5) -0.0014(3) 0.0036(3) -0.0005(3) C5 0.0116(4) 0.0159(4) 0.0141(5) 0.0007(4) 0.0034(4) -0.0009(3) C6 0.0125(5) 0.0178(4) 0.0139(5) 0.0002(4) 0.0047(4) -0.0011(3) C7 0.0144(5) 0.0149(4) 0.0167(5) -0.0020(4) 0.0039(4) -0.0013(3) C8 0.0149(5) 0.0177(4) 0.0199(5) -0.0023(4) 0.0065(4) -0.0002(4) C32 0.0138(5) 0.0142(4) 0.0161(5) 0.0008(4) 0.0036(4) -0.0012(3) C10 0.0149(5) 0.0142(4) 0.0232(6) 0.0003(4) 0.0042(4) -0.0005(4) C11 0.0138(5) 0.0138(4) 0.0223(6) -0.0001(4) 0.0049(4) 0.0003(3) C12 0.0136(5) 0.0204(5) 0.0241(6) -0.0007(4) 0.0040(4) -0.0026(4) O2 0.0261(5) 0.0390(5) 0.0357(5) 0.0110(4) 0.0175(4) 0.0153(4) C14 0.0169(5) 0.0220(5) 0.0167(5) -0.0028(4) 0.0063(4) 0.0020(4) C15 0.0150(5) 0.0140(4) 0.0194(5) -0.0011(4) 0.0052(4) -0.0006(3) C16 0.0124(4) 0.0155(4) 0.0132(5) 0.0011(3) 0.0024(4) -0.0008(3) C17 0.0125(5) 0.0235(5) 0.0171(5) -0.0022(4) 0.0039(4) -0.0019(4) C18 0.0181(5) 0.0229(5) 0.0207(6) -0.0030(4) 0.0102(4) -0.0012(4) C19 0.0157(5) 0.0169(4) 0.0145(5) -0.0032(4) 0.0034(4) 0.0001(4) C20 0.0141(5) 0.0174(4) 0.0150(5) -0.0007(4) 0.0049(4) -0.0010(3) C21 0.0134(5) 0.0221(4) 0.0155(5) -0.0009(4) 0.0053(4) -0.0001(4) C22 0.0178(5) 0.0309(6) 0.0185(5) 0.0008(4) 0.0086(4) 0.0001(4) C23 0.0139(5) 0.0267(5) 0.0232(6) -0.0008(4) 0.0092(4) -0.0001(4) C24 0.0150(5) 0.0253(5) 0.0185(5) -0.0007(4) 0.0070(4) -0.0010(4) C25 0.0149(5) 0.0273(5) 0.0203(6) -0.0011(4) 0.0058(4) 0.0036(4) C26 0.0272(7) 0.0295(6) 0.0251(7) 0.0019(5) 0.0085(5) 0.0081(5) C27 0.0184(5) 0.0370(6) 0.0244(6) 0.0011(5) 0.0125(5) 0.0051(5) C28 0.0193(5) 0.0267(5) 0.0262(6) -0.0036(5) 0.0132(5) -0.0033(4) _geom_special_details ; All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. ; loop_ _geom_bond_atom_site_label_1 _geom_bond_atom_site_label_2 _geom_bond_distance _geom_bond_site_symmetry_2 _geom_bond_publ_flag S1 C6 1.7146(11) . ? S1 C28 1.7338(12) . ? O1 C16 1.3514(12) . ? O1 C7 1.4446(13) . ? N4 C19 1.3667(13) . ? N4 C6 1.3783(14) . ? N4 C5 1.3986(13) . ? N3 C16 1.2984(14) . ? N3 C20 1.3923(13) . ? N2 C10 1.4636(14) . ? N2 C8 1.4655(14) . ? N2 C12 1.4679(14) . ? C5 C21 1.3853(15) . ? C5 C16 1.4336(14) . ? C6 C20 1.3762(14) . ? C7 C32 1.5176(15) . ? C7 H5 0.984(14) . ? C7 H6 0.980(14) . ? C8 C15 1.5188(15) . ? C8 H14 1.023(14) . ? C8 H13 0.991(15) . ? C32 C15 1.5275(15) . ? C32 C11 1.5315(15) . ? C32 H9 1.010(14) . ? C10 C11 1.5277(15) . ? C10 H12 0.990(15) . ? C10 H16 1.041(14) . ? C11 H11 0.993(14) . ? C11 H10 0.988(15) . ? C12 C17 1.5078(16) . ? C12 H15 0.976(15) . ? C12 H17 0.996(15) . ? O2 C25 1.3687(14) . ? O2 C26 1.4138(17) . ? C14 C19 1.3797(16) . ? C14 C21 1.4092(15) . ? C14 H2 0.963(15) . ? C15 H8 0.977(14) . ? C15 H7 0.997(14) . ? C17 C23 1.3930(16) . ? C17 C22 1.3940(16) . ? C18 C28 1.3575(16) . ? C18 C20 1.4307(16) . ? C18 H4 0.960(15) . ? C19 H3 0.939(15) . ? C21 H1 0.964(15) . ? C22 C27 1.3825(17) . ? C22 H20 0.980(15) . ? C23 C24 1.3948(16) . ? C23 H18 0.953(15) . ? C24 C25 1.3934(16) . ? C24 H19 0.982(15) . ? C25 C27 1.3937(18) . ? C26 H23 1.005(18) . ? C26 H25 0.993(18) . ? C26 H24 1.006(18) . ? C27 H22 0.970(17) . ? C28 H21 0.971(16) . ? loop_ _geom_angle_atom_site_label_1 _geom_angle_atom_site_label_2 _geom_angle_atom_site_label_3 _geom_angle _geom_angle_site_symmetry_1 _geom_angle_site_symmetry_3 _geom_angle_publ_flag C6 S1 C28 89.81(5) . . ? C16 O1 C7 116.73(8) . . ? C19 N4 C6 131.87(9) . . ? C19 N4 C5 109.34(9) . . ? C6 N4 C5 118.79(9) . . ? C16 N3 C20 115.89(9) . . ? C10 N2 C8 109.28(9) . . ? C10 N2 C12 109.65(8) . . ? C8 N2 C12 111.43(9) . . ? C21 C5 N4 107.34(9) . . ? C21 C5 C16 135.79(10) . . ? N4 C5 C16 116.87(9) . . ? C20 C6 N4 119.89(9) . . ? C20 C6 S1 113.68(8) . . ? N4 C6 S1 126.43(8) . . ? O1 C7 C32 107.40(9) . . ? O1 C7 H5 109.7(8) . . ? C32 C7 H5 109.8(8) . . ? O1 C7 H6 108.6(8) . . ? C32 C7 H6 112.9(8) . . ? H5 C7 H6 108.3(11) . . ? N2 C8 C15 109.70(9) . . ? N2 C8 H14 111.3(8) . . ? C15 C8 H14 110.3(8) . . ? N2 C8 H13 107.4(8) . . ? C15 C8 H13 111.2(8) . . ? H14 C8 H13 106.9(11) . . ? C7 C32 C15 110.61(8) . . ? C7 C32 C11 110.29(9) . . ? C15 C32 C11 109.57(9) . . ? C7 C32 H9 108.7(8) . . ? C15 C32 H9 108.7(8) . . ? C11 C32 H9 109.0(8) . . ? N2 C10 C11 111.51(8) . . ? N2 C10 H12 107.9(8) . . ? C11 C10 H12 109.4(8) . . ? N2 C10 H16 109.2(8) . . ? C11 C10 H16 109.9(8) . . ? H12 C10 H16 108.8(11) . . ? C10 C11 C32 111.74(9) . . ? C10 C11 H11 108.6(8) . . ? C32 C11 H11 109.7(8) . . ? C10 C11 H10 109.4(9) . . ? C32 C11 H10 110.4(9) . . ? H11 C11 H10 106.8(12) . . ? N2 C12 C17 112.60(9) . . ? N2 C12 H15 105.5(8) . . ? C17 C12 H15 110.6(9) . . ? N2 C12 H17 110.9(9) . . ? C17 C12 H17 109.0(9) . . ? H15 C12 H17 108.1(12) . . ? C25 O2 C26 118.54(10) . . ? C19 C14 C21 108.56(10) . . ? C19 C14 H2 125.5(9) . . ? C21 C14 H2 125.9(9) . . ? C8 C15 C32 112.14(9) . . ? C8 C15 H8 110.0(8) . . ? C32 C15 H8 110.1(8) . . ? C8 C15 H7 109.2(8) . . ? C32 C15 H7 108.8(8) . . ? H8 C15 H7 106.5(11) . . ? N3 C16 O1 121.36(9) . . ? N3 C16 C5 125.39(9) . . ? O1 C16 C5 113.25(9) . . ? C23 C17 C22 117.71(11) . . ? C23 C17 C12 121.83(10) . . ? C22 C17 C12 120.46(11) . . ? C28 C18 C20 111.89(10) . . ? C28 C18 H4 123.6(9) . . ? C20 C18 H4 124.4(9) . . ? N4 C19 C14 107.64(9) . . ? N4 C19 H3 120.7(9) . . ? C14 C19 H3 131.6(8) . . ? C6 C20 N3 123.13(10) . . ? C6 C20 C18 111.18(10) . . ? N3 C20 C18 125.68(10) . . ? C5 C21 C14 107.11(10) . . ? C5 C21 H1 125.7(9) . . ? C14 C21 H1 127.2(8) . . ? C27 C22 C17 121.53(11) . . ? C27 C22 H20 119.5(9) . . ? C17 C22 H20 118.9(9) . . ? C17 C23 C24 121.83(11) . . ? C17 C23 H18 117.8(9) . . ? C24 C23 H18 120.4(9) . . ? C25 C24 C23 119.09(11) . . ? C25 C24 H19 123.1(9) . . ? C23 C24 H19 117.8(9) . . ? O2 C25 C24 124.69(11) . . ? O2 C25 C27 115.47(10) . . ? C24 C25 C27 119.84(11) . . ? O2 C26 H23 111.8(10) . . ? O2 C26 H25 112.2(10) . . ? H23 C26 H25 105.6(14) . . ? O2 C26 H24 104.6(10) . . ? H23 C26 H24 110.4(14) . . ? H25 C26 H24 112.4(14) . . ? C22 C27 C25 119.94(11) . . ? C22 C27 H22 121.9(10) . . ? C25 C27 H22 118.2(10) . . ? C18 C28 S1 113.44(9) . . ? C18 C28 H21 128.0(10) . . ? S1 C28 H21 118.5(10) . . ? _diffrn_measured_fraction_theta_max 0.999 _diffrn_reflns_theta_full 33.18 _diffrn_measured_fraction_theta_full 0.999 _refine_diff_density_max 0.430 _refine_diff_density_min -0.306 _refine_diff_density_rms 0.057 _publ_section_abstract ; The synthesis of novel pyrrolothienopyrazines has been achieved with the aim to bring together in a sole compound both an AChE inhibitory effect and a 5-HT~4~R agonist activity. These Multi-Target Directed Ligands might theoretically alleviate the cognitive deficit in Alzheimer disease by restoring the cholinergic activity and by promoting the non-amyloidogenic formation of sAPP\a which seems detrimental to the amyloid aggregation. Some of the synthesized compounds bear these dual activities and compound 15b appears particularly potent towards both AChE and 5-HT~4~R targets with IC~50~ and Ki in nanomolar levels. The molecular modeling study we further achieved led to propose a first dual pharmacophore. The latter will be very useful to design further MTDL with therapeutic interest in AD treatment. ;