Compound characterization data — Wijffelaars et al., 2026

Laura H.A. Wijffelaars, Maurice C.M.L. Buzink, Tomasz M. Stepniewski, Britt Hurks, Desislava Nesheva, Susanne M.A. van der Pol, István Szabó, Luna Melo Alcerreca, Henry F. Vischer, Merel Rijnsburger, Maikel Wijtmans, Yaroslav V. Nikolaev, Helga E. de Vries, Iwan J.P. de Esch, Rob Leurs. “Diastereomer-dependent modulation of atypical chemokine receptor 3 (ACKR3) in 3-azabicyclo[3.1.0]hexane-based ligands.” ChemRxiv (2026). https://doi.org/10.26434/chemrxiv.15007510/v1

Supporting information is appended to the main paper

N-(1-cyclohexylpiperidin-4-yl)-5-(2,4-difluorophenyl)-1,2-oxazole-3-carboxamide
Identifier	1
HPLC-MS (acidic mode)	Rt 3.69 min, LC purity 97 %, m/z [M + H]⁺ calculated 390.20, found 390.15
¹H NMR (500 MHz, DMSO-d₆)	δ 8.75 (d, J = 8.1 Hz, 1H), 8.05 (ddd, J = 8.7, 8.7, 6.3 Hz, 1H), 7.59 (ddd, J = 11.6, 9.3, 2.6 Hz, 1H), 7.37–7.29 (m, 1H), 7.16 (d, J = 3.1 Hz, 1H), 3.78–3.66 (m, 1H), 2.85–2.78 (m, 1H), 2.28–2.19 (m, 3H), 1.79–1.65 (m, 6H), 1.60–1.49 (m, 3H), 1.24–1.13 (m, 4H), 1.12–1.01 (m, 1H)
¹³C NMR (126 MHz, DMSO-d₆)	164.0, 163.7 (dd, J = 256.5, 12.2 Hz), 159.7, 159.0 (dd, J = 256.5, 12.2 Hz), 157.6, 129.7 (dd, J = 10.7, 3.4 Hz), 113.0 (dd, J = 21.8, 3.6 Hz), 111.5 (dd, J = 12.5, 3.9 Hz), 105.5 (dd, J = 25.9, 25.9 Hz), 102.6 (d, J = 8.2 Hz), 62.9, 47.8, 47.4, 31.8, 28.8, 26.0, 25.6
HRMS, m/z [M + H]⁺	C21H26F2N3O2+ calculated 390.1988, found 390.1994

N-((1R,3s,5S)-8-cyclohexyl-8-azabicyclo[3.2.1]octan-3-yl)-5-(2,4-difluorophenyl)isoxazole-3-carboxamide
Identifier	4
UPLC-MS (acidic mode)	Rt 1.63 min, LC purity 97 % (254 nm), m/z [M + H]⁺ calculated 416.21, found 416.55
¹H NMR (600 MHz, DMSO-d₆)	δ 8.37–8.18 (m, 1H), 8.05 (ddd, J = 8.7, 8.7, 6.3 Hz, 1H), 7.58 (ddd, J = 11.5, 9.2, 2.5 Hz, 1H), 7.36–7.29 (m, 1H), 7.14 (d, J = 2.8 Hz, 1H), 4.04–3.98 (m, 1H), 3.55–3.37 (m, 2H), 2.42–2.24 (m, 1H), 2.12–1.98 (m, 2H), 1.94–1.79 (m, 6H), 1.75–1.64 (m, 4H), 1.57–1.51 (m, 1H), 1.26–1.19 (m, 2H), 1.17–1.04 (m, 3H)
¹³C NMR (151 MHz, DMSO)	δ 164.5 (d, J = 2.8 Hz), 164.1 (dd, J = 251.9, 12.5 Hz), 160.3, 159.5 (dd, J = 255.8, 12.5 Hz), 158.5, 130.1 (dd, J = 10.4, 3.4 Hz), 113.5 (dd, J = 22.1, 3.4 Hz), 111.9 (dd, J = 12.5, 3.8 Hz), 106.0 (dd, J = 25.9, 25.9 Hz), 102.9 (d, J = 8.3 Hz), 53.9, 53.1, 42.7, 32.2, 31.6, 27.0, 26.2, 24.7
HRMS, m/z [M + H]⁺	C15H16F2N3O2+ calculated 416.2144, found 416.2144

N-((1R,3r,5S)-8-cyclohexyl-8-azabicyclo[3.2.1]octan-3-yl)-5-(2,4-difluorophenyl)isoxazole-3-carboxamide
Identifier	5
UPLC-MS (acidic mode)	Rt 1.63 min, LC purity 97 % (254 nm), m/z [M + H]⁺ calculated 416.21, found 416.55
¹H NMR (500 MHz, DMSO-d₆)	δ 8.72 (d, J = 8.4 Hz, 1H), 8.05 (ddd, J = 8.7, 8.7, 6.3 Hz, 1H), 7.57 (ddd, J = 11.6, 9.3, 2.6 Hz, 1H), 7.35–7.30 (m, 1H), 7.14 (d, J = 3.0 Hz, 1H), 4.27–4.16 (m, 1H), 3.49–3.42 (m, 2H), 2.69–2.59 (m, 1H), 1.90–1.83 (m, 2H), 1.83–1.75 (m, 3H), 1.75–1.66 (m, 3H), 1.62–1.52 (m, 3H), 1.47–1.38 (m, 2H), 1.31–1.20 (m, 2H), 1.20–1.10 (m, 1H), 1.10–0.99 (m, 2H)
¹³C NMR (126 MHz, DMSO)	δ 163.9 (dd, J = 2.6, 0.8 Hz), 163.6 (d, J = 264.4 Hz), 159.7, 158.6 (dd, J = 255.5, 12.7 Hz), 157.1, 129.6 (dd, J = 10.4, 3.3 Hz), 113.0 (dd, J = 22.3, 3.4 Hz), 111.5 (dd, J = 12.6, 3.9 Hz), 105.5 (dd, J = 26.0, 26.0 Hz), 102.4 (d, J = 8.3 Hz), 52.9, 51.9, 41.1, 32.0, 31.2, 27.4, 25.8, 24.3
HRMS, m/z [M + H]⁺	C15H16F2N3O2+ calculated 416.2144, found 416.2144

N-((1R,5S,6r)-3-cyclohexyl-3-azabicyclo[3.1.0]hexan-6-yl)-5-(2,4-difluorophenyl)isoxazole-3-carboxamide
Identifiers	6, VUF26199
UPLC-MS (acidic mode)	Rt 1.42 min, LC purity >99 % (254 nm), m/z [M + H]⁺ calculated 388.18, found 388.45
¹H NMR (600 MHz, DMSO-d₆)	δ 8.68 (d, J = 9.0 Hz, 1H), 8.08 (ddd, J = 8.5, 8.5, 6.2 Hz, 1H), 7.58 (ddd, J = 11.3, 8.9, 2.1 Hz, 1H), 7.35–7.28 (m, 1H), 7.11 (d, J = 2.6 Hz, 1H), 3.57 (dt, J = 9.3, 7.4 Hz, 1H), 3.08 (d, J = 9.5 Hz, 2H), 2.63 (d, J = 9.2 Hz, 2H), 2.24–2.15 (m, 1H), 1.77–1.63 (m, 6H), 1.50–1.44 (m, 1H), 1.39–1.18 (m, 5H)
¹³C NMR (151 MHz, DMSO)	δ 164.6, 163.7 (dd, J = 252.2, 12.6 Hz), 159.4, 159.0 (dd, J = 255.7, 12.8 Hz), 158.4, 129.8 (dd, J = 10.4, 3.1 Hz), 113.0 (dd, J = 22.0, 3.3 Hz), 111.4 (dd, J = 12.2, 4.0 Hz), 105.5 (dd, J = 26.0, 26.0 Hz), 102.2 (d, J = 8.3 Hz), 60.4, 49.6, 31.0, 30.7, 25.7, 23.1, 18.8
HRMS, m/z [M + H]⁺	C21H24F2N3O2+ calculated 388.1831, found 388.1837

Tert-butyl (1R,5S,6s)-6-(5-(2,4-difluorophenyl)isoxazole-3-carboxamido)-3-azabicyclo[3.1.0]hexane-3-carboxylate
Identifier	9
UPLC-MS (acidic mode)	Rt 2.07 min, LC purity 89 % (254 nm), m/z [M + H]⁺ calculated 406.10, 306.16 without Boc and 350.10 without t-Bu, found 306.00 and 349.95
¹H NMR (500 MHz, DMSO-d₆)	δ 9.04 (d, J = 4.3 Hz, 1H), 8.05 (ddd, J = 8.6, 8.6, 6.5 Hz, 1H), 7.57 (ddd, J = 11.5, 9.2, 2.4 Hz, 1H), 7.33 (ddd, J = 8.5, 8.5, 2.1 Hz, 1H), 7.14 (d, J = 2.9 Hz, 1H), 3.52 (d, J = 10.8 Hz, 2H), 3.39–3.34 (m, 2H), 2.54 (dt, J = 4.6, 2.6 Hz, 1H), 1.88–1.81 (m, 2H), 1.39 (s, 9H)

N-((1R,5S,6s)-3-azabicyclo[3.1.0]hexan-6-yl)-5-(2,4-difluorophenyl)isoxazole-3-carboxamidehydrochloride
Identifier	10.HCl
UPLC-MS (acidic mode)	Rt 1.40 min, LC purity 96 % (254 nm), m/z [M + H]⁺ calculated 306.16, found 305.95
¹H NMR (500 MHz, DMSO-d₆)	δ 9.73–9.52 (m, 1H), 9.12 (d, J = 4.3 Hz, 1H), 9.09–8.96 (m, 1H), 8.05 (ddd, J = 8.7, 8.7, 6.5 Hz, 1H), 7.58 (ddd, J = 11.5, 9.4, 2.4 Hz, 1H), 7.33 (ddd, J = 8.4, 8.4, 2.1 Hz, 1H), 7.17 (d, J = 2.9 Hz, 1H), 3.44–3.36 (m, 2H), 3.37–3.26 (m, 2H), 3.08 (dt, J = 4.8, 3.0 Hz, 1H), 2.07 (s, 2H)

N-((1R,5S,6s)-3-azabicyclo[3.1.0]hexan-6-yl)-5-(2,4-difluorophenyl)isoxazole-3-carboxamidefumarate
Identifier	10.FuA
UPLC-MS (acidic mode)	Rt 1.40 min, LC purity 96 % (254 nm), m/z [M + H]⁺ calculated 306.10, found 306.55
¹H NMR (600 MHz, DMSO-d₆)	δ 8.96 (d, J = 4.5 Hz, 1H), 8.05 (ddd, J = 8.7, 8.6, 6.3 Hz, 1H), 7.57 (ddd, J = 11.5, 9.2, 2.5 Hz, 1H), 7.36–7.29 (m, 1H), 7.14 (d, J = 2.9 Hz, 1H), 6.43 (s, 1H), 3.14 (d, J = 11.4 Hz, 2H), 2.97 (d, J = 11.3 Hz, 2H), 2.85 (dt, J = 4.8, 2.5 Hz, 1H), 1.81 (ddd, J = 2.5, 2.5, 1.1 Hz, 2H)
¹³C NMR (151 MHz, DMSO)	δ 167.9, 164.0 (d, J = 2.6 Hz), 163.7 (dd, J = 252.1, 12.4 Hz), 159.4, 159.0 (dd, J = 255.2, 12.7 Hz), 158.8, 135.1, 129.6 (dd, J = 10.7, 3.2 Hz), 113.0 (dd, J = 22.0, 3.4 Hz), 111.4 (dd, J = 12.4, 3.9 Hz), 105.5 (dd, J = 25.9, 25.9 Hz), 102.4 (d, J = 8.3 Hz), 47.2, 29.6, 23.8
HRMS, m/z [M + H]⁺	C15H14F2N3O2+ calculated 306.1049, found 306.1043

N-((1R,5S,6s)-3-cyclohexyl-3-azabicyclo[3.1.0]hexan-6-yl)-5-(2,4-difluorophenyl)isoxazole-3-carboxamide
Identifiers	7, VUF26200
UPLC-MS (acidic mode)	Rt 1.50 min, LC purity 97 % (254 nm), m/z [M + H]⁺ calculated 388.18, found 388.05
¹H NMR (600 MHz, DMSO-d₆)	δ 8.87 (d, J = 4.8 Hz, 1H), 8.05 (ddd, J = 8.7, 8.7, 6.4 Hz, 1H), 7.58 (ddd, J = 11.5, 9.3, 2.5 Hz, 1H), 7.32 (ddd, J = 8.4, 8.4, 2.2 Hz, 1H), 7.13 (d, J = 2.9 Hz, 1H), 3.08 (d, J = 8.7 Hz, 2H), 3.01–2.98 (m, 1H), 2.33 (d, J = 8.4 Hz, 2H), 2.02 (tt, J = 9.4, 3.5 Hz, 1H), 1.78–1.72 (m, 2H), 1.69–1.61 (m, 4H), 1.54–1.47 (m, 1H), 1.24–1.09 (m, 5H)
¹³C NMR (151 MHz, DMSO)	δ 163.96 (d, J = 2.4 Hz), 163.66 (dd, J = 251.8, 12.5 Hz), 159.48, 159.00 (dd, J = 255.2, 12.9 Hz), 158.80, 129.63 (dd, J = 10.4, 3.2 Hz), 113.02 (dd, J = 22.1, 3.4 Hz), 111.47 (dd, J = 12.2, 3.9 Hz), 105.52 (dd, J = 25.9, 25.9 Hz), 102.44 (d, J = 8.4 Hz), 61.29, 51.45, 31.29, 30.08, 25.75, 24.12, 22.60
HRMS, m/z [M + H]⁺	C21H24F2N3O2+ calculated 388.1831, found 388.1843

5-(2,4-difluorophenyl)-N-((1R,5S,6s)-3-(tetrahydro-2H-pyran-4-yl)-3-azabicyclo[3.1.0]hexan-6-yl) isoxazole-3-carboxamide
Identifier	11
UPLC-MS (acidic mode)	Rt 1.33 min, LC purity >99 % (254 nm), m/z [M + H]⁺ calculated 390.16, found 390.45
¹H NMR (500 MHz, DMSO-d₆)	δ 8.86 (d, J = 4.9 Hz, 1H), 8.05 (ddd, J = 8.7, 8.7, 6.3 Hz, 1H), 7.57 (ddd, J = 11.6, 9.2, 2.6 Hz, 1H), 7.32 (ddd, J = 8.6, 8.5, 2.5 Hz, 1H), 7.13 (d, J = 2.9 Hz, 1H), 3.81 (ddd, J = 11.6, 3.5, 3.5 Hz, 2H), 3.27 (ddd, J = 11.6, 11.5, 2.2 Hz, 3H), 3.08 (d, J = 8.7 Hz, 2H), 3.01 (dt, J = 4.7, 2.2 Hz, 1H), 2.34 (d, J = 8.5 Hz, 2H), 2.22 (tt, J = 10.4, 3.9 Hz, 1H), 1.73–1.65 (m, 4H), 1.33 (dddd, J = 12.7, 11.9, 11.5, 4.3 Hz, 2H)
¹³C NMR (126 MHz, DMSO)	δ 163.93 (d, J = 2.5 Hz), 163.64 (dd, J = 255.7, 12.8 Hz), 159.43, 158.97 (dd, J = 255.5, 12.6 Hz), 158.77, 129.61 (d, J = 10.4 Hz), 112.96 (dd, J = 22.1, 3.3 Hz), 111.44 (dd, J = 12.8, 3.6 Hz), 105.46 (dd, J = 26.0, 26.0 Hz), 102.39 (d, J = 8.2 Hz), 65.56, 58.99, 51.22, 31.91, 30.04, 22.46
HRMS, m/z [M + H]⁺	C20H22F2N3O3+ calculated 390.1624, found 390.1635

Tert-butyl 4-((1R,5S,6r)-6-(5-(2,4-difluorophenyl)isoxazole-3-carboxamido)-3-azabicyclo[3.1.0]hexan-3-yl)piperidine-1-carboxylate
Identifier	12
UPLC-MS (acidic mode)	Rt 1.55 min, LC purity 97 % (254 nm), m/z [M + H]⁺ calculated 489.23, found 489.55
¹H NMR (500 MHz, DMSO-d₆)	δ 8.89 (d, J = 4.8 Hz, 1H), 8.05 (ddd, J = 8.7, 8.7, 6.3 Hz, 1H), 7.58 (ddd, J = 11.5, 9.2, 2.6 Hz, 1H), 7.32 (ddd, J = 8.6, 8.5, 2.6 Hz, 1H), 7.13 (d, J = 3.0 Hz, 1H), 3.84–3.69 (m, 2H), 3.08 (d, J = 8.7 Hz, 2H), 3.00 (dt, J = 4.7, 2.2 Hz, 1H), 2.90–2.76 (m, 2H), 2.35 (d, J = 8.9 Hz, 2H), 2.18 (tt, J = 9.9, 3.6 Hz, 1H), 1.74–1.66 (m, 4H), 1.38 (s, 9H), 1.24–1.17 (m, 2H)
¹³C NMR (126 MHz, DMSO)	δ 163.94, 163.64 (dd, J = 251.8, 11.9 Hz), 159.44, 158.98 (dd, J = 256.2, 14.6 Hz), 158.78, 153.86, 129.61 (dd, J = 10.1, 2.9 Hz), 112.98 (dd, J = 22.1, 3.0 Hz), 111.45 (d, J = 7.7 Hz), 105.48 (dd, J = 25.9, 25.9 Hz), 102.41 (d, J = 8.2 Hz), 78.49, 59.34, 51.42, 41.36#, 30.61#, 30.06, 28.08, 22.55

5-(2,4-difluorophenyl)-N-((1R,5S,6s)-3-(piperidin-4-yl)-3-azabicyclo[3.1.0]hexan-6-yl)isoxazole-3-carboxamide
Identifier	13
UPLC-MS (acidic mode)	Rt 1.23 min, LC purity 96 % (254 nm), m/z [M + H]⁺ calculated 389.18, found 389.20
¹H NMR (500 MHz, DMSO-d₆)	δ 8.85 (d, J = 4.9 Hz, 1H), 8.04 (ddd, J = 8.7, 8.7, 6.3 Hz, 1H), 7.57 (ddd, J = 11.5, 9.2, 2.6 Hz, 1H), 7.32 (ddd, J = 8.5, 8.3, 2.2 Hz, 1H), 7.12 (d, J = 2.9 Hz, 1H), 3.07 (d, J = 8.7 Hz, 2H), 3.00 (dt, J = 4.6, 2.2 Hz, 1H), 2.88 (ddd, J = 12.5, 3.7, 3.7 Hz, 2H), 2.39 (ddd, J = 12.0, 11.9, 2.5 Hz, 2H), 2.32 (d, J = 8.6 Hz, 2H), 2.05 (tt, J = 10.4, 3.8 Hz, 1H), 1.71–1.63 (m, 4H), 1.17 (dddd, J = 12.3, 11.5, 11.5, 4.0 Hz, 2H)
¹³C NMR (126 MHz, DMSO)	δ 163.91 (d, J = 1.9 Hz), 163.62 (dd, J = 251.7, 12.7 Hz), 159.43, 158.96 (dd, J = 255.3, 13.0 Hz), 158.76, 129.59 (dd, J = 10.4, 3.5 Hz), 112.95 (dd, J = 22.1, 3.5 Hz), 111.44 (d, J = 8.6 Hz), 105.45 (dd, J = 25.9, 25.9 Hz), 102.39 (d, J = 8.4 Hz), 60.60, 51.21, 44.76, 32.14, 30.04, 22.47
HRMS, m/z [M + H]⁺	C20H23F2N4O2+ calculated 389.1784, found 389.1774

5-(2,4-difluorophenyl)-N-((1R,5S,6s)-3-(1-methylpiperidin-4-yl)-3-azabicyclo[3.1.0]hexan-6-yl)isoxazole-3-carboxamide
Identifier	14
UPLC-MS (acidic mode)	Rt 1.24 min, LC purity 99 % (254 nm), m/z [M + H]⁺ calculated 403.19, found 403.50
¹H NMR (500 MHz, DMSO-d₆)	δ 8.87 (d, J = 4.8 Hz, 1H), 8.04 (ddd, J = 8.7, 8.7, 6.3 Hz, 1H), 7.58 (ddd, J = 11.6, 9.2, 2.5 Hz, 1H), 7.32 (ddd, J = 8.6, 8.3, 2.1 Hz, 1H), 7.13 (d, J = 2.9 Hz, 1H), 3.07 (d, J = 8.7 Hz, 2H), 3.00 (dt, J = 4.6, 2.2 Hz, 1H), 2.70–2.62 (m, 2H), 2.31 (d, J = 8.7 Hz, 2H), 2.10 (s, 3H), 1.93 (tt, J = 10.2, 3.8 Hz, 1H), 1.83 (ddd, J = 12.6, 10.9, 1.9 Hz, 2H), 1.73–1.65 (m, 4H), 1.32 (dddd, J = 12.3, 12.3, 11.1, 3.9 Hz, 2H)
¹³C NMR (126 MHz, DMSO)	δ 163.93 (d, J = 2.3 Hz), 163.63 (dd, J = 252.0, 12.6 Hz), 159.43, 158.97 (dd, J = 255.2, 12.8 Hz), 158.77, 129.60 (dd, J = 10.4, 3.4 Hz), 112.97 (dd, J = 22.1, 3.5 Hz), 111.45 (dd, J = 12.5, 3.9 Hz), 105.47 (dd, J = 25.9, 25.9 Hz), 102.40 (d, J = 8.4 Hz), 59.71, 53.90, 51.58, 45.96, 30.92, 30.05, 22.56
HRMS, m/z [M + H]⁺	C21H25F2N4O2+ calculated 403.1940, found 403.1930

5-(2,4-difluorophenyl)-N-((1R,5S,6s)-3-methyl-3-azabicyclo[3.1.0]hexan-6-yl)isoxazole-3-carboxamide
Identifier	15
UPLC-MS (acidic mode)	Rt 1.30 min, LC purity 98 % (254 nm), m/z [M + H]⁺ calculated 320.12, found 319.95
¹H NMR (500 MHz, DMSO-d₆)	δ 8.87 (d, J = 4.8 Hz, 1H), 8.04 (ddd, J = 8.7, 8.7, 6.3 Hz, 1H), 7.57 (ddd, J = 11.5, 9.2, 2.5 Hz, 1H), 7.32 (ddd, J = 8.5, 8.4, 2.5 Hz, 1H), 7.12 (d, J = 3.0 Hz, 1H), 3.07 (dt, J = 4.7, 2.2 Hz, 1H), 2.99 (d, J = 8.8 Hz, 2H), 2.29–2.23 (m, 2H), 2.21 (s, 3H), 1.70–1.62 (m, 2H)
¹³C NMR (126 MHz, DMSO)	δ 163.91 (d, J = 2.3 Hz), 163.63 (dd, J = 252.1, 12.7 Hz), 159.45, 158.97 (dd, J = 255.4, 12.8 Hz), 158.78, 129.59 (dd, J = 10.4, 3.2 Hz), 112.97 (dd, J = 22.1, 3.5 Hz), 111.45 (dd, J = 12.2, 4.0 Hz), 105.48 (dd, J = 25.9, 25.9 Hz), 102.40 (d, J = 8.5 Hz), 56.01, 40.77, 29.94, 23.29
HRMS, m/z [M + H]⁺	C16H16F2N3O2+ calculated 320.1205, found 320.1200

5-(2,4-difluorophenyl)-N-((1R,5S,6s)-3-ethyl-3-azabicyclo[3.1.0]hexan-6-yl)isoxazole-3-carboxamide
Identifier	16
UPLC-MS (acidic mode)	Rt 1.24 min, LC purity 97 % (254 nm), m/z [M + H]⁺ calculated 334.14, found 334.05
¹H NMR (500 MHz, DMSO-d₆)	δ 8.87 (d, J = 4.9 Hz, 1H), 8.04 (ddd, J = 8.7, 8.7, 6.3 Hz, 1H), 7.57 (ddd, J = 11.5, 9.2, 2.5 Hz, 1H), 7.32 (ddd, J = 8.5, 8.3, 2.2 Hz, 1H), 7.13 (d, J = 3.0 Hz, 1H), 3.08–3.02 (m, 3H), 2.38 (q, J = 7.2 Hz, 2H), 2.25 (d, J = 8.8 Hz, 2H), 1.69–1.64 (m, 2H), 0.98 (t, J = 7.2 Hz, 3H)
¹³C NMR (126 MHz, DMSO)	δ 163.91 (d, J = 1.9 Hz), 163.63 (dd, J = 251.9, 12.5 Hz), 159.44, 158.97 (dd, J = 255.2, 13.1 Hz), 158.77, 129.59 (dd, J = 10.4, 3.2 Hz), 112.97 (dd, J = 22.1, 3.5 Hz), 111.45 (dd, J = 12.4, 3.9 Hz), 105.47 (dd, J = 26.0, 26.0 Hz), 102.40 (d, J = 8.6 Hz), 53.72, 48.46, 29.98, 22.65, 13.83
HRMS, m/z [M + H]⁺	C17H18F2N3O2+ calculated 334.1362, found 334.1354

5-(2,4-difluorophenyl)-N-((1R,5S,6s)-3-propyl-3-azabicyclo[3.1.0]hexan-6-yl)isoxazole-3-carboxamide
Identifier	17
UPLC-MS (acidic mode)	Rt 1.38 min, LC purity 99 % (254 nm), m/z [M + H]⁺ calculated 348.15, found 348.15
¹H NMR (500 MHz, DMSO-d₆)	δ 8.87 (d, J = 4.5 Hz, 1H), 8.04 (ddd, J = 8.7, 8.7, 6.4 Hz, 1H), 7.57 (ddd, J = 11.5, 9.2, 2.5 Hz, 1H), 7.32 (ddd, J = 8.6, 8.3, 2.2 Hz, 1H), 7.12 (d, J = 3.0 Hz, 1H), 3.07–3.01 (m, 3H), 2.30 (t, J = 7.4 Hz, 2H), 2.27–2.23 (m, 2H), 1.70–1.63 (m, 2H), 1.39 (tq, J = 7.3, 7.3 Hz, 2H), 0.83 (t, J = 7.3 Hz, 3H)
¹³C NMR (126 MHz, DMSO)	δ 163.91 (d, J = 2.8 Hz), 163.63 (dd, J = 252.2, 12.5 Hz), 159.44, 158.97 (dd, J = 255.2, 12.7 Hz), 158.77, 129.58 (dd, J = 10.4, 3.3 Hz), 112.97 (dd, J = 22.2, 3.6 Hz), 111.45 (dd, J = 12.4, 3.8 Hz), 105.47 (dd, J = 26.0, 26.0 Hz), 102.40 (d, J = 8.4 Hz), 56.48, 54.00, 30.02, 22.69, 21.51, 11.75
HRMS, m/z [M + H]⁺	C18H20F2N3O2+ calculated 348.1518, found 348.1512

5-(2,4-difluorophenyl)-N-((1R,5S,6s)-3-isopropyl-3-azabicyclo[3.1.0]hexan-6-yl)isoxazole-3-carboxamide
Identifier	18
UPLC-MS (acidic mode)	Rt 1.34 min, LC purity 99 % (254 nm), m/z [M + H]⁺ calculated 348.15, found 348.15
¹H NMR (500 MHz, DMSO-d₆)	δ 8.86 (d, J = 4.9 Hz, 1H), 8.04 (ddd, J = 8.7, 8.7, 6.3 Hz, 1H), 7.57 (ddd, J = 11.5, 9.3, 2.5 Hz, 1H), 7.32 (ddd, J = 8.5, 8.4, 2.5 Hz, 1H), 7.13 (d, J = 2.9 Hz, 1H), 3.07–3.00 (m, 3H), 2.41–2.29 (m, 3H), 1.69–1.64 (m, 2H), 0.97 (d, J = 6.3 Hz, 6H)
¹³C NMR (126 MHz, DMSO)	δ 163.91 (d, J = 1.8 Hz), 163.63 (dd, J = 252.2, 12.4 Hz), 159.44, 158.97 (dd, J = 255.3, 12.7 Hz), 158.76, 129.58 (dd, J = 10.2, 3.4 Hz), 112.97 (dd, J = 22.0, 3.5 Hz), 111.45 (dd, J = 12.4, 3.9 Hz), 105.47 (dd, J = 26.0, 26.0 Hz), 102.40 (d, J = 8.6 Hz), 53.04, 51.66, 30.02, 22.73, 21.45
HRMS, m/z [M + H]⁺	C18H20F2N3O2+ calculated 348.1518, found 348.1521

5-(2,4-difluorophenyl)-N-((1R,5S,6s)-3-neopentyl-3-azabicyclo[3.1.0]hexan-6-yl)isoxazole-3-carboxamide
Identifier	19
UPLC-MS (acidic mode)	Rt 1.48 min, LC purity 99 % (254 nm), m/z [M + H]⁺ calculated 376.18, found 376.50
¹H NMR (500 MHz, DMSO-d₆)	δ 8.86 (d, J = 4.7 Hz, 1H), 8.05 (ddd, J = 8.7, 8.7, 6.4 Hz, 1H), 7.57 (ddd, J = 11.6, 9.3, 2.6 Hz, 1H), 7.32 (ddd, J = 8.1, 8.0, 1.9 Hz, 1H), 7.12 (d, J = 3.0 Hz, 1H), 3.08 (d, J = 8.7 Hz, 2H), 3.05 (dt, J = 4.6, 2.3 Hz, 1H), 2.50–2.47 (m, 2H), 2.17 (s, 2H), 1.68–1.64 (m, 2H), 0.83 (s, 9H)
¹³C NMR (126 MHz, DMSO)	δ 163.92 (d, J = 1.8 Hz), 163.63 (dd, J = 251.9, 12.4 Hz), 159.45, 158.97 (dd, J = 255.2, 12.7 Hz), 158.80, 129.60 (dd, J = 10.4, 3.3 Hz), 112.97 (dd, J = 22.2, 3.6 Hz), 111.45 (dd, J = 12.4, 3.8 Hz), 105.47 (dd, J = 26.0, 26.0 Hz), 102.38 (d, J = 8.5 Hz), 67.08, 56.78, 32.67, 30.20, 28.06, 23.10
HRMS, m/z [M + H]⁺	C20H24F2N3O2+ calculated 376.1831, found 376.1822

N-((1R,5S,6s)-3-cyclobutyl-3-azabicyclo[3.1.0]hexan-6-yl)-5-(2,4-difluorophenyl)isoxazole-3-carboxamide
Identifier	20
UPLC-MS (acidic mode)	Rt 1.42 min, LC purity >99 % (254 nm), m/z [M + H]⁺ calculated 360.15, found 360.45
¹H NMR (500 MHz, DMSO-d₆)	δ 8.85 (d, J = 4.9 Hz, 1H), 8.04 (ddd, J = 8.7, 8.7, 6.4 Hz, 1H), 7.56 (ddd, J = 11.5, 9.3, 2.5 Hz, 1H), 7.32 (ddd, J = 8.3, 8.3, 2.1 Hz, 1H), 7.12 (d, J = 3.0 Hz, 1H), 3.08–3.03 (m, 1H), 2.99–2.90 (m, 3H), 2.27 (d, J = 8.2 Hz, 2H), 1.94–1.85 (m, 2H), 1.86–1.75 (m, 2H), 1.70–1.53 (m, 4H)
¹³C NMR (126 MHz, DMSO)	δ 163.9 (d, J = 2.4 Hz), 163.6 (dd, J = 252.1, 12.5 Hz), 159.4, 159.0 (dd, J = 255.2, 12.8 Hz), 158.8, 129.6 (dd, J = 10.4, 3.3 Hz), 113.0 (dd, J = 22.1, 3.4 Hz), 111.4 (dd, J = 12.4, 3.8 Hz), 105.5 (dd, J = 26.0, 26.0 Hz), 102.4 (d, J = 8.4 Hz), 57.3, 50.4, 30.0, 26.7, 22.7, 14.8
HRMS, m/z [M + H]⁺	C19H20F2N3O2+ calculated 360.1518, found 360.1522

N-((1R,5S,6s)-3-cyclopentyl-3-azabicyclo[3.1.0]hexan-6-yl)-5-(2,4-difluorophenyl)isoxazole-3-carboxamide
Identifier	21
UPLC-MS (acidic mode)	Rt 1.44 min, LC purity 97 % (254 nm), m/z [M + H]⁺ calculated 374.17, found 374.50
¹H NMR (500 MHz, DMSO-d₆)	δ 8.84 (d, J = 4.9 Hz, 1H), 8.04 (ddd, J = 8.7, 8.7, 6.4 Hz, 1H), 7.57 (ddd, J = 11.5, 9.3, 2.5 Hz, 1H), 7.32 (ddd, J = 8.5, 8.4, 2.1 Hz, 1H), 7.12 (d, J = 3.0 Hz, 1H), 3.08–3.00 (m, 3H), 2.43 (tt, J = 7.7, 7.4 Hz, 1H), 2.29 (d, J = 8.5 Hz, 2H), 1.72–1.52 (m, 6H), 1.52–1.41 (m, 2H), 1.38–1.27 (m, 2H)
¹³C NMR (126 MHz, DMSO)	δ 163.9 (d, J = 1.9 Hz), 163.6 (dd, J = 251.8, 12.2 Hz), 159.4, 159.0 (dd, J = 255.3, 12.7 Hz), 158.7, 129.6 (dd, J = 10.4, 3.3 Hz), 113.0 (dd, J = 22.1, 3.4 Hz), 111.4 (dd, J = 12.4, 3.9 Hz), 105.5 (dd, J = 26.0, 26.0 Hz), 102.4 (d, J = 8.0 Hz), 65.5, 53.4, 31.5, 30.0, 23.4, 22.7
HRMS, m/z [M + H]⁺	C20H22F2N3O2+ calculated 374.1675, found 374.1674

N-((1R,5S,6s)-3-cycloheptyl-3-azabicyclo[3.1.0]hexan-6-yl)-5-(2,4-difluorophenyl)isoxazole-3-carboxamide
Identifier	22
UPLC-MS (acidic mode)	Rt 1.43 min, LC purity 96 % (254 nm), m/z [M + H]⁺ calculated 402.20, found 402.50
¹H NMR (500 MHz, DMSO-d₆)	δ 8.84 (d, J = 4.8 Hz, 1H), 8.04 (ddd, J = 8.7, 8.7, 6.4 Hz, 1H), 7.56 (ddd, J = 11.6, 9.2, 2.5 Hz, 1H), 7.32 (ddd, J = 8.5, 8.4, 2.5 Hz, 1H), 7.12 (d, J = 3.0 Hz, 1H), 3.05–2.97 (m, 3H), 2.41–2.30 (m, 3H), 1.69–1.54 (m, 6H), 1.54–1.45 (m, 6H), 1.41–1.30 (m, 2H)
¹³C NMR (126 MHz, DMSO)	δ 163.89 (d, J = 2.2 Hz), 163.61 (dd, J = 251.9, 12.3 Hz), 159.44, 158.96 (dd, J = 255.0, 12.9 Hz), 158.75, 129.58 (dd, J = 10.4, 3.2 Hz), 112.95 (dd, J = 21.9, 3.5 Hz), 111.44 (dd, J = 12.5, 3.9 Hz), 105.45 (dd, J = 25.9, 25.9 Hz), 102.37 (d, J = 8.3 Hz), 61.82, 50.98, 31.88, 30.05, 27.85, 23.63, 22.61
HRMS, m/z [M + H]⁺	C22H26F2N3O2+ calculated 402.1988, found 402.2000

N-((1R,5S,6s)-3-(cyclopropylmethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-5-(2,4-difluorophenyl)isoxazole-3-carboxamide
Identifier	23
UPLC-MS (acidic mode)	Rt 1.25 min, LC purity 97 % (254 nm), m/z [M + H]⁺ calculated 360.15, found 360.40
¹H NMR (500 MHz, DMSO-d₆)	δ 8.85 (d, J = 4.9 Hz, 1H), 8.04 (ddd, J = 8.7, 8.7, 6.3 Hz, 1H), 7.56 (ddd, J = 11.6, 9.2, 2.6 Hz, 1H), 7.32 (ddd, J = 8.5, 8.3, 2.5 Hz, 1H), 7.13 (d, J = 3.0 Hz, 1H), 3.14–3.06 (m, 3H), 2.31 (d, J = 8.7 Hz, 2H), 2.22 (d, J = 6.7 Hz, 2H), 1.69–1.65 (m, 2H), 0.85–0.74 (m, 1H), 0.46–0.38 (m, 2H), 0.08–0.01 (m, 2H)
¹³C NMR (126 MHz, DMSO)	δ 163.90 (d, J = 1.9 Hz), 163.62 (dd, J = 251.9, 12.3 Hz), 159.43, 158.96 (dd, J = 255.3, 12.7 Hz), 158.77, 129.58 (dd, J = 10.3, 3.4 Hz), 112.95 (dd, J = 22.1, 3.6 Hz), 111.44 (dd, J = 12.4, 3.8 Hz), 105.45 (dd, J = 26.0, 26.0 Hz), 102.39 (d, J = 8.5 Hz), 59.10, 54.00, 29.96, 22.69, 9.79, 3.45
HRMS, m/z [M + H]⁺	C19H20F2N3O2+ calculated 360.1518, found 360.1536

N-((1R,5S,6s)-3-(cyclobutylmethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-5-(2,4-difluorophenyl)isoxazole-3-carboxamide
Identifier	24
UPLC-MS (acidic mode)	Rt 1.36 min, LC purity 95 % (254 nm), m/z [M + H]⁺ calculated 374.17, found 347.35
¹H NMR (500 MHz, DMSO-d₆)	δ 8.84 (d, J = 4.9 Hz, 1H), 8.04 (ddd, J = 8.7, 8.7, 6.3 Hz, 1H), 7.56 (ddd, J = 11.6, 9.3, 2.5 Hz, 1H), 7.32 (ddd, J = 8.7, 8.4, 2.8 Hz, 1H), 7.12 (d, J = 3.0 Hz, 1H), 3.03 (dt, J = 4.7, 2.2 Hz, 1H), 2.98 (d, J = 8.8 Hz, 2H), 2.43–2.34 (m, 3H), 2.28 (d, J = 8.8 Hz, 2H), 2.03–1.93 (m, 2H), 1.89–1.70 (m, 2H), 1.69–1.54 (m, 4H)
¹³C NMR (126 MHz, DMSO)	δ 163.90 (d, J = 2.7 Hz), 163.62 (dd, J = 252.0, 12.7 Hz), 159.42, 158.96 (dd, J = 255.2, 12.8 Hz), 158.75, 129.58 (dd, J = 10.5, 3.3 Hz), 112.95 (dd, J = 22.2, 3.6 Hz), 111.43 (d, J = 8.9 Hz), 105.45 (dd, J = 26.0, 26.0 Hz), 102.38 (d, J = 8.3 Hz), 60.73, 54.22, 34.59, 30.01, 26.61, 22.72, 18.15
HRMS, m/z [M + H]⁺	C20H22F2N3O2+ calculated 374.1675, found 374.1676

N-((1R,5S,6s)-3-(cyclopentylmethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-5-(2,4-difluorophenyl) isoxazole-3-carboxamide
Identifier	25
UPLC-MS (acidic mode)	Rt 1.34 min, LC purity 99 % (254 nm), m/z [M + H]⁺ calculated 388.18, found 388.45
¹H NMR (500 MHz, DMSO-d₆)	δ 8.84 (d, J = 4.9 Hz, 1H), 8.04 (ddd, J = 8.7, 8.7, 6.3 Hz, 1H), 7.56 (ddd, J = 11.5, 9.3, 2.6 Hz, 1H), 7.31 (ddd, J = 8.5, 8.3, 2.2 Hz, 1H), 7.12 (d, J = 3.0 Hz, 1H), 3.08–3.02 (m, 3H), 2.34–2.20 (m, 4H), 1.95 (ttt, J = 7.5, 7.5, 7.5 Hz, 1H), 1.71–1.60 (m, 4H), 1.58–1.40 (m, 4H), 1.19–1.09 (m, 2H)
¹³C NMR (126 MHz, DMSO)	δ 163.91 (d, J = 2.3 Hz), 163.62 (dd, J = 251.9, 12.4 Hz), 159.43, 158.96 (dd, J = 255.3, 12.7 Hz), 158.77, 129.58 (dd, J = 10.4, 3.4 Hz), 112.95 (dd, J = 22.2, 3.6 Hz), 111.44 (dd, J = 12.4, 3.8 Hz), 105.45 (dd, J = 26.0, 26.0 Hz), 102.38 (d, J = 8.2 Hz), 60.22, 54.27, 38.40, 30.48, 30.07, 24.72, 22.72
HRMS, m/z [M + H]⁺	C21H24F2N3O2+ calculated 388.1831, found 388.1835

N-((1R,5S,6s)-3-(cyclohexylmethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-5-(2,4-difluorophenyl)isoxazole-3-carboxamide
Identifier	26
UPLC-MS (acidic mode)	Rt 1.54 min, LC purity 99 % (254 nm), m/z [M + H]⁺ calculated 402.20, found 402.50
¹H NMR (500 MHz, DMSO-d₆)	δ 8.85 (d, J = 4.7 Hz, 1H), 8.04 (ddd, J = 8.7, 8.7, 6.5 Hz, 1H), 7.57 (ddd, J = 11.5, 9.3, 2.4 Hz, 1H), 7.32 (ddd, J = 8.4, 8.4, 2.1 Hz, 1H), 7.12 (d, J = 2.9 Hz, 1H), 3.09–2.92 (m, 3H), 2.25 (d, J = 8.2 Hz, 2H), 2.17 (d, J = 7.3 Hz, 2H), 1.75–1.56 (m, 7H), 1.36 (ttt, J = 10.6, 6.9, 3.5 Hz, 1H), 1.25–1.06 (m, 3H), 0.80 (ddd, J = 10.9, 10.9, 10.0 Hz, 2H)
¹³C NMR (126 MHz, DMSO)	δ 163.9 (d, J = 1.8 Hz), 163.6 (dd, J = 252.0, 12.6 Hz), 159.4, 159.0 (dd, J = 255.2, 13.9 Hz), 158.8, 129.6 (dd, J = 10.4, 3.5 Hz), 113.0 (dd, J = 22.2, 3.2 Hz), 111.5 (dd, J = 12.4, 4.0 Hz), 105.5 (dd, J = 25.9, 25.9 Hz), 102.4 (d, J = 8.5 Hz), 61.5, 54.3, 36.4, 31.2, 30.1, 26.4, 25.5, 22.7
HRMS, m/z [M + H]⁺	C22H26F2N3O2+ calculated 402.1988, found 402.1992

N-((1R,5S,6s)-3-benzyl-3-azabicyclo[3.1.0]hexan-6-yl)-5-(2,4-difluorophenyl)isoxazole-3-carboxamide
Identifier	27
UPLC-MS (acidic mode)	Rt 1.49 min, LC purity 97 % (254 nm), m/z [M + H]⁺ calculated 396.15, found 396.40
¹H NMR (500 MHz, DMSO-d₆)	δ 8.86 (d, J = 4.8 Hz, 1H), 8.04 (ddd, J = 8.7, 8.7, 6.4 Hz, 1H), 7.57 (ddd, J = 11.5, 9.3, 2.5 Hz, 1H), 7.35–7.29 (m, 3H), 7.29–7.21 (m, 3H), 7.12 (d, J = 3.0 Hz, 1H), 3.57 (s, 2H), 3.14 (dt, J = 4.7, 2.4 Hz, 1H), 2.98 (d, J = 8.8 Hz, 2H), 2.37 (d, J = 8.5 Hz, 2H), 1.69 (s, 2H)
¹³C NMR (126 MHz, DMSO)	δ 163.92 (d, J = 2.7 Hz), 163.62 (dd, J = 251.7, 12.5 Hz), 159.42, 158.96 (dd, J = 255.1, 12.7 Hz), 158.79, 139.06, 129.60 (d, J = 13.8 Hz), 128.22 (d, J = 18.6 Hz), 126.80, 112.96 (dd, J = 22.2, 3.6 Hz), 111.44 (dd, J = 12.3, 4.1 Hz), 105.46 (dd, J = 25.9, 25.9 Hz), 102.38 (d, J = 8.4 Hz), 58.07, 53.63, 30.00, 22.75
HRMS, m/z [M + H]⁺	C22H20F2N3O2+ calculated 396.1518, found 396.1521