Spectroscopic differentiation and chromatographic separation of regioisomeric indole aldehydes: Synthetic cannabinoids precursors

Younis Abiedallaa,, Lewis W. Smithc, Karim M. Abdel-Haya,d,e, Logan Neela, Tarek S. Belala,e,Amber Thaxton-Weissenfluha, Forrest Smitha, Jack DeRuitera, C. Randall Clarka,⁎
Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA
Department of Medicinal Chemistry, Faculty of Pharmacy, Omar Al-Mukhtar University, El-Beida, Libya
Forensic Spectral Research, Bridgeton, NJ 08302, USA
Department of Chemistry, College of Science, Eastern Kentucky University, Richmond, KY 40475, USA
Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt

 

 

Introduction
Research related to drug structure and cannabinoid receptor affinity has identified the general molecular features for this drug class [1–4] consisting of a heterocyclic ring core, a small polar linker connected to a lipophilic head-group and a flexible hydrophobic side-chain [1].

 

These structural requirements are evident in 1-n-pentyl-3-(1-naphthoyl)-indole (JWH-018), one of the first five controlled synthetic cannabinoid drugs [5]. This molecule contains the indole ring core and a carbonyl linker at the 3-position bonded to the naphthyl group creating this diarylketone with the side-chain n-pentyl alkyl group at the indole 1-position. Thus conforming to the general structural features described for cannabinoid receptor affinity.

 

The most reactive position on the indole ring toward electrophilic substitution is the carbon at the 3-position and this position on the pyrrole portion of the indole ring displays very high reactivity toward electrophilic aromatic substitution [2,6,7]. The indole nitrogen has relatively low nucleophilicity and is essentially unreactive due to delocalization of its non-bonded pair of electrons into the aromatic system which activates the 3-position. However, the indole nitrogen can be deprotonated to enhance its nucleophilicity and allow it to react with electrophiles to form 1-substituted products [8]. Indoles that already contain a substitutent at the 1-position undergo electrophilic substitution exclusively at the 3-position. Thus, direct substitution reactions for indoles occur only on the pyrrole-portion of this heterocyclic ring system and the six-membered benzene ring is not significantly reactive toward direct electrophilic aromatic substitution reactions. The traditional 1,3-disubstituted indole based cannabinoids are typically prepared by synthetic strategies taking advantage of the activated 1- and 3-positions. The alkyl side-chain group can be added to the indole nitrogen via nucleophilic displacement of the halide group from alkylhalides such as 1-bromopentane [7,9,10]. Acylation of the 3-position of indole with various acyl halides (such as 1-naphthoylchloride) using Friedel-Crafts catalysts such as dimethyl-aluminum chloride allows the addition of the linker carbonyl and the naphthyl head-group.

 

The incorporation of numerous core heterocyclic ring systems into the general synthetic cannabinoid molecular scaffolding along with many side-chains, linkers and liphophilic head-groups has produced a
wide variety of new drug-like substances [6,7,10,11]. Combinations of these structural features has led to cannabinoid receptor studies on hundreds of compounds and likely provided the basic information for the development of many of the synthetic cannabinoid drugs of abuse[12].

 

Among the recent indole replacement core structures is the (9H)-carbazole heterocyclic system, which is an indole-like system containing an additional fused benzene ring across the 2,3-carbons of indole (benzo-2,3-indole) [1]. One compound containing this new heterocyclic core is 3-(1-naphthoyl)-9-pentyl-(9H-carbazole) also known as EG-018 and it can be viewed as the carbazole equivalent of the
classic indole synthetic cannabinoid JWH-018 [1]. These two molecules, JWH-018 and EG-018 display similar binding profiles and low nanomolar affinities for the cannabinoid receptors [1]. The naphthoyl
group substituent at the 3-position of the (9H)-carbazole ring is attached to the benzene ring portion of the heterocyclic core and para to the nitrogen of this ring system. The 3-position of carbazole is equivalent to the 5-position of the indole with the naphthoyl group substituted para to the aromatic nitrogen atom in each ring system.

 

Thus, the relatively high cannabinoid receptor binding affinity in EG-018 suggests the possibility for activity in indoles with the head-group substituted on the benzene ring portion of the indole molecular scaffolding at position 5 or 6. Recent report [13] has extended the chemical structure and cannabinoid receptor activity relationship data for the indoles beyond the traditional 1,3-substitution pattern and included the placement of the head-group at each of the six remaining available indole ring substitution positions. The direct regioisomers of JWH-018 having the naphthoyl group at the indole 5-position and 6-position have cannabinoid receptor ED50 values essentially equivalent to that for JWH-018 [13].

 

The addition of the acyl group to the benzene ring portion of indole can be accomplished from the appropriately substituted indole aldehyde. Aryl magnesium halides (Grignard reagents) addition across the carbonyl double bond [14–16] and mild oxidation of the secondary alcohol intermediate yields the carbonyl linker and aryl head-group at varying positions of the indole ring. All the required regioisomeric precursor indole aldehydes are commercially available and undergo the Grignard-type synthetic processes to yield indoles with the acyl group substituted at each of the possible ring indole positions.

 

The study described in this report has evaluated the regioisomeric 2-, 3-, 4-, 5-, 6- and 7-formylindoles as well as the six corresponding Nn-pentylindole aldehydes. These aldehydes represent the starting materials and synthetic intermediates for the preparation of many regioisomeric indoles having the head-group located on the benzene ring portion of this heterocyclic ring. These structure-property relationship studies will provide an analytical framework for the identification of individual aldehydes in this study based on GC–MS and GC–IR techniques.

 

Experimental
Instrumentation
GC–MS system consisted of an Agilent Technologies (Santa Clara, CA) 7890A gas chromatograph and an Agilent 7683B auto injector coupled with a 5975C VL Agilent mass selective detector. The mass spectral scan rate was 2.86 scans/s. The GC was operated in splitless mode with a helium (ultra-high purity, grade 5, 99.999%) flow rate of 0.48 ml/min and the column head pressure was 10 psi. The MS was
operated in the electron ionization (EI) mode using an ionization voltage of 70 eV and a source temperature of 230 °C. The GC injector was maintained at 300 °C and the transfer line at 230 °C. The mass spectra and chromatographic separations were obtained using a column (30 m × 0.25 mm i.d.) coated with 0.25 μm film of midpolarity Crossbond® silarylene phase; similar to 50% phenyl, 50% dimethyl
polysiloxane (Rxi®-17Sil MS) purchased from Restek Corporation (Bellefonte, PA). The chromatographic separation and the mass spectra of the six intermediate 1-n-pentylindole aldehydes were obtained using a temperature program consisting of an initial hold at 80 °C for 1.0 min, ramped up to 300 °C at a rate of 30 °C/min, held at 300 °C for 0.50 min then ramped to 340 °C at a rate of 5 °C/min and held at 340 °C for 5.0 min. The chromatographic separation and the mass spectra of the six precursor indole aldehydes were obtained using a temperature program consisting of an initial hold at 100 °C for 1.0 min, ramped up to 300 °C at a rate of 10 °C/min, held at 300 °C for 0.50 min then ramped to 340 °C at a rate of 5 °C/min and held at 340 °C for 5.0 min. Samples were dissolved and diluted in high-performance liquid chromatography-grade acetonitrile (Fisher Scientific, Fairlawn, NJ) and introduced via the auto injector using an injection volume of 1-μl.

 

GC–IR studies were carried out on a Hewlett-Packard 6890 Series gas chromatograph and a Hewlett-Packard 7683 series auto-injector coupled with an IRD-3 detector obtained from Analytical Solutions and
Providers (ASAP), Covington, KY. The vapor phase infrared detector (IRD) spectra were recorded in the range of 4000 to 550 cm−1 with a resolution of 16 cm−1 and a scan rate 1.50 scans/s. The GC injector was maintained at 250 °C and the transfer line A, the light pipe and the transfer line B temperatures were maintained at 250 °C. The GC was operated in the split injection mode (split ratio of 10:1) with a carrier gas helium (ultra-high purity, grade 5, 99.999%) flow rate of 2 ml/minute and the column head pressure was 2.62 psi. The stationary phase used was a 6 m × 0.32 mm i.d. capillary column coated with
1.0 µm film of 5% Phenyl Polysilphenylene-siloxane (BPX5) purchased from SGE Analytical Science (Austin, TX). The temperature program consisted of an initial temperature of 70 °C for 1.0 min, ramped up to 370 °C at a rate of 30 °C/min followed by a hold at 370 °C for 8.0 min.

 

Samples were dissolved and diluted in high-performance liquid chromatography-grade acetonitrile (Fisher Scientific, Fairlawn, NJ) and introduced via the auto injector using an injection volume of 1-μl.

 

Synthetic methods
1-n-Pentylindole aldehydes
Indoles 3-, 4-, 5- and 7-carboxaldehydes were purchased from Alfa Aesar Chemical Company, Ward Hill, MA. Indoles 2- and 6-carboxaldehydes were purchased from Aldrich Chemical Company, Milwaukee, WI. A mixture of potassium hydroxide (KOH) and a solution of the appropriately aldehyde substituted indole in dimethylformamide was stirred under nitrogen for 30.0 min. 1-bromopentane was added to the substituted indole/potassium hydroxide mixture and the resulting solution was stirred for 2 h. The mixture was poured into water and extracted with ethyl acetate. The combined ethyl acetate extracts were washed with water, dried over sodium sulfate and evaporated to yield the desired intermediate 1-n-pentylindole aldehyde product [9]. The resulting compounds were purified by flash chromatography with a 10:90 diethyl ether-petroleum ether solution as the mobile phase, using Sorbtech (Norcross, GA) purity flash cartridges (granular silica gel, 25 g).
 

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1-Benzyl-3,3-difluoropiperidin-4-amine Catalog No.:AA009KLS CAS No.:1039741-55-3 MDL No.:MFCD18433632 MF:C12H16F2N2 MW:226.2656	2-Bromo-4-fluoro-1-(methylsulfonyl)benzene Catalog No.:AA007F5N CAS No.:1039744-23-4 MDL No.:MFCD13195736 MF:C7H6BrFO2S MW:253.0887
MK-4074 Catalog No.:AA01EOED CAS No.:1039758-22-9 MDL No.:MFCD31630723 MF:C33H31N3O6 MW:565.6157	1-Cyclopropyl-1h-pyrrole-2-carbaldehyde Catalog No.:AA009627 CAS No.:1039758-67-2 MDL No.:MFCD12181369 MF:C8H9NO MW:135.1632
1,3-diethyl 2-{[(2,5-dimethylphenyl)amino]methylidene}propanedioate Catalog No.:AA00IPK8 CAS No.:103976-09-6 MDL No.:MFCD00173355 MF:C16H21NO4 MW:291.3422	Diethyl 2-((3-chloro-4-methylphenylamino)methylene)malonate Catalog No.:AA003PCJ CAS No.:103976-11-0 MDL No.:MFCD00487335 MF:C15H18ClNO4 MW:311.7607
1,3-diethyl 2-{[(4-chloro-2-methylphenyl)amino]methylidene}propanedioate Catalog No.:AA00IQIS CAS No.:103976-13-2 MDL No.:MFCD00111154 MF:C15H18ClNO4 MW:311.7607	1,3-diethyl 2-{[(2-chloro-4-methylphenyl)amino]methylidene}propanedioate Catalog No.:AA00IQ01 CAS No.:103976-15-4 MDL No.:MFCD00173391 MF:C15H18ClNO4 MW:311.7607
3-Pyridinecarboxamide,2-(methylamino)-(9CI) Catalog No.:AA009SII CAS No.:103976-52-9 MDL No.:MFCD11052030 MF:C7H9N3O MW:151.1659	ethyl 2-(methylamino)pyridine-3-carboxylate Catalog No.:AA019TIX CAS No.:103976-61-0 MDL No.:MFCD11119739 MF:C9H12N2O2 MW:180.2038
Dimethyl 1-(2-oxopropyl)-1h-1,2,3-triazole-4,5-dicarboxylate Catalog No.:AA00HA5Q CAS No.:1039766-69-2 MDL No.:MFCD22549283 MF:C9H11N3O5 MW:241.2007	4-{[(4-chlorophenyl)methyl]sulfanyl}aniline Catalog No.:AA00IWSV CAS No.:103977-34-0 MDL No.:MFCD02755408 MF:C13H12ClNS MW:249.7591
2-Bromo-1,3-difluoro-4-nitrobenzene Catalog No.:AA008V6V CAS No.:103977-78-2 MDL No.:MFCD12545882 MF:C6H2BrF2NO2 MW:237.9864	3-Bromo-2,4-difluoroaniline Catalog No.:AA008V0U CAS No.:103977-79-3 MDL No.:MFCD12407090 MF:C6H4BrF2N MW:208.0035
2-Methoxy-6-p-tolylpyridine Catalog No.:AA007F5L CAS No.:1039775-38-6 MDL No.:MFCD18914538 MF:C13H13NO MW:199.2484	2'-Fluorobiphenyl-3-carboxylic acid Catalog No.:AA00853G CAS No.:103978-23-0 MDL No.:MFCD03424610 MF:C13H9FO2 MW:216.2078
2-Bromo-1-fluoro-3-hydroxy-4-nitrobenzene Catalog No.:AA008VJU CAS No.:103979-08-4 MDL No.:MFCD18071060 MF:C6H3BrFNO3 MW:235.9953	1H-Thieno[2,3-d][1,3]oxazine-2,4-dione Catalog No.:AA0090BB CAS No.:103979-54-0 MDL No.:MFCD18380600 MF:C6H3NO3S MW:169.1579
Ceftiofur, HCl Catalog No.:AA00HA5T CAS No.:103980-44-5 MDL No.:MFCD30187701 MF:C19H18ClN5O7S3 MW:560.0235	6-amino-5-ethyl-2-methyl-3,4-dihydropyrimidin-4-one Catalog No.:AA01AUE7 CAS No.:103980-51-4 MDL No.:MFCD18363801 MF:C7H11N3O MW:153.1817
6-Methyl-5-propylpyrimidin-4(1H)-one Catalog No.:AA003N7R CAS No.:103980-68-3 MDL No.:MFCD01689111 MF:C8H12N2O MW:152.1937	3-methyl-5-(trifluoromethyl)aniline hydrochloride Catalog No.:AA01B534 CAS No.:103981-82-4 MDL No.:MFCD29991935 MF:C8H9ClF3N MW:211.6120
2-({5-[(2,3-dimethylphenyl)amino]-1,3,4-thiadiazol-2-yl}sulfanyl)acetic acid Catalog No.:AA01A4M0 CAS No.:1039810-14-4 MDL No.:MFCD12532387 MF:C12H13N3O2S2 MW:295.3805	3-[(Pyrimidin-2-ylsulfanyl)methyl]-1-benzofuran-2-carboxylic acid Catalog No.:AA019Y0X CAS No.:1039812-24-2 MDL No.:MFCD13358734 MF:C14H10N2O3S MW:286.3058
2-(4-hydroxyphenyl)-2-(methylamino)acetonitrile Catalog No.:AA01BRIN CAS No.:1039815-62-7 MDL No.:MFCD11186582 MF:C9H10N2O MW:162.1885	3-(Methylthio)-1-(3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)propan-1-amine Catalog No.:AA01C6CX CAS No.:1039815-72-9 MDL No.:MFCD11125263 MF:C11H14N4OS MW:250.3201
2-Amino-6-chloro-3-fluorobenzoic acid Catalog No.:AA0092CF CAS No.:1039815-76-3 MDL No.:MFCD11183542 MF:C7H5ClFNO2 MW:189.5715	2-(3-bromophenoxy)-5-chloroaniline Catalog No.:AA01C1EM CAS No.:1039816-97-1 MDL No.:MFCD11125277 MF:C12H9BrClNO MW:298.5630
3-Methyl-1-[3-(4h-1,2,4-triazol-3-yl)-1,2,4-oxadiazol-5-yl]butan-1-amine Catalog No.:AA01A1RL CAS No.:1039823-99-8 MDL No.:MFCD11125447 MF:C9H14N6O MW:222.2471	(R)-tert-Butyl 2-(bromomethyl)pyrrolidine-1-carboxylate Catalog No.:AA007F5B CAS No.:1039826-29-3 MDL No.:MFCD12912139 MF:C10H18BrNO2 MW:264.1594
1-(5-bromo-2-fluorophenyl)-2,2,2-trifluoroethan-1-ol Catalog No.:AA01ABAK CAS No.:1039827-16-1 MDL No.:MFCD16067891 MF:C8H5BrF4O MW:273.0223	3-amino-N-(5-chloropyridin-2-yl)benzamide Catalog No.:AA01AGY5 CAS No.:1039827-87-6 MDL No.:MFCD11184857 MF:C12H10ClN3O MW:247.6803
6-(Phenylsulfanyl)-3-pyridinamine Catalog No.:AA00HA5X CAS No.:103983-07-9 MDL No.:MFCD03230019 MF:C11H10N2S MW:202.2755	4-methyl-3-oxoheptanenitrile Catalog No.:AA01AKU6 CAS No.:1039833-22-1 MDL No.:MFCD11187377 MF:C8H13NO MW:139.1949
3-Cyclobutyl-1,2-oxazol-5-amine Catalog No.:AA00HA5Y CAS No.:1039833-39-0 MDL No.:MFCD11187392 MF:C7H10N2O MW:138.1671	3-[2-(furan-2-yl)ethyl]-1,2-oxazol-5-amine Catalog No.:AA01A9QH CAS No.:1039833-44-7 MDL No.:MFCD11187393 MF:C9H10N2O2 MW:178.1879
(3-Cyclohexyl-1,2,4-oxadiazol-5-yl)methylamine hydrochloride Catalog No.:AA007WSC CAS No.:1039837-72-3 MDL No.:MFCD12027095 MF:C9H15N3O MW:181.2349	N-Methyl-1-phenyl-1h-pyrazolo[3,4-d]pyrimidin-4-amine Catalog No.:AA01A9UR CAS No.:103984-27-6 MDL No.:MFCD11204655 MF:C12H11N5 MW:225.2492
N-(pyridin-2-ylmethyl)pyridin-4-amine Catalog No.:AA01A3XD CAS No.:1039840-86-2 MDL No.:MFCD11125394 MF:C11H11N3 MW:185.2251	Ethyl 2-(2,5-dichlorophenyl)sulfanylacetate Catalog No.:AA01FAQL CAS No.:1039844-00-2 MDL No.:MFCD11174591 MF:C10H10Cl2O2S MW:265.1562
2-(Chloromethyl)thieno[2,3-d]pyrimidin-4(1H)-one Catalog No.:AA019TDB CAS No.:1039847-82-9 MDL No.:MFCD22207562 MF:C7H5ClN2OS MW:200.6454	1-Cyclohexene-1-methanol, 2,4,4-trimethyl- Catalog No.:AA007F58 CAS No.:103985-40-6 MDL No.:MFCD28714754 MF:C10H18O MW:154.2493
5-(5-Bromopyridin-3-yl)-1,3,4-oxadiazol-2-amine Catalog No.:AA018MT3 CAS No.:1039851-68-7 MDL No.:MFCD11194661 MF:C7H5BrN4O MW:241.0448	N-(3-fluorobenzyl)urea Catalog No.:AA00J6P6 CAS No.:1039852-38-4 MDL No.:MFCD11192631 MF:C8H9FN2O MW:168.1683
[2-(4-Propoxyphenoxy)pyridin-3-yl]methanamine Catalog No.:AA019UYH CAS No.:1039855-27-0 MDL No.:MFCD11858081 MF:C15H18N2O2 MW:258.3156	2-chloro-6-(2,2,3,3-tetrafluoropropoxy)pyrazine Catalog No.:AA019XVL CAS No.:1039858-65-5 MDL No.:MFCD11197521 MF:C7H5ClF4N2O MW:244.5740
N-(2-Aminoethyl)-2,5-dibromobenzene-1-sulfonamide Catalog No.:AA01AH1A CAS No.:1039858-71-3 MDL No.:MFCD11189705 MF:C8H10Br2N2O2S MW:358.0502	5-(3-chlorophenyl)-4-methylthiophene-2-carboxylic acid Catalog No.:AA01A9EC CAS No.:1039859-49-8 MDL No.:MFCD11189723 MF:C12H9ClO2S MW:252.7167
5-[4-(Trifluoromethoxy)phenyl]thiophene-2-carboxylic acid Catalog No.:AA01ABCY CAS No.:1039859-73-8 MDL No.:MFCD12739572 MF:C12H7F3O3S MW:288.2424	2,3-Dimethyl-1h-indole-6-carboxylic acid Catalog No.:AA008S87 CAS No.:103986-06-7 MDL No.:MFCD06799503 MF:C11H11NO2 MW:189.2105
2,3-Dimethyl-1h-indole-7-carboxylic acid Catalog No.:AA008V75 CAS No.:103986-07-8 MDL No.:MFCD00090259 MF:C11H11NO2 MW:189.2105	6-Methoxyindole-3-acetic acid Catalog No.:AA00853A CAS No.:103986-22-7 MDL No.:MFCD01548400 MF:C11H11NO3 MW:205.2099
4-Methylnaphthalene-1-boronic acid Catalog No.:AA007F57 CAS No.:103986-53-4 MDL No.:MFCD01632204 MF:C11H11BO2 MW:186.0148	Cyclopropanecarboxylic acid, 2-(phenylmethyl)- Catalog No.:AA007WS7 CAS No.:103986-55-6 MDL No.:MFCD16744627 MF:C11H12O2 MW:176.2118
2,3-dimethyl-2,3-dihydro-1-benzofuran-7-carboxylic acid Catalog No.:AA019OSD CAS No.:103986-71-6 MDL No.:MFCD03426823 MF:C11H12O3 MW:192.2112	Trans-3-ethoxycinnamic acid Catalog No.:AA003UUI CAS No.:103986-73-8 MDL No.:MFCD00016843 MF:C11H12O3 MW:192.2112
1-Hydroxy-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid Catalog No.:AA01A6X0 CAS No.:103986-80-7 MDL No.:MFCD20638931 MF:C11H12O3 MW:192.2112	3-(Chloromethyl)-5-(tetrahydro-2-furanyl)-1,2,4-oxadiazole Catalog No.:AA007WS9 CAS No.:1039860-29-1 MDL No.:MFCD25976754 MF:C7H9ClN2O2 MW:188.6116
3-[(2-phenylethoxy)methyl]aniline Catalog No.:AA019XS1 CAS No.:1039862-68-4 MDL No.:MFCD11196403 MF:C15H17NO MW:227.3016	5-[(3,4-dichlorophenyl)methyl]-2H-1,2,3,4-tetrazole Catalog No.:AA01E8DT CAS No.:1039864-56-6 MDL No.:MFCD19352653 MF:C8H6Cl2N4 MW:229.0660
1-(4-Bromophenyl)-2-pyridin-2-ylethanamine Catalog No.:AA019R0P CAS No.:1039865-46-7 MDL No.:MFCD11188769 MF:C13H13BrN2 MW:277.1597	1-(3-Bromo-4-methoxyphenyl)-2,2,2-trifluoroethanamine Catalog No.:AA01ABI7 CAS No.:1039867-83-8 MDL No.:MFCD07384639 MF:C9H9BrF3NO MW:284.0731
4-(aminomethyl)-N,N-diethyl-2-fluoroaniline Catalog No.:AA01AGUL CAS No.:1039868-26-2 MDL No.:MFCD11191619 MF:C11H17FN2 MW:196.2645	3-fluoro-4-[2-(trifluoromethyl)phenoxy]aniline Catalog No.:AA019XQT CAS No.:1039868-92-2 MDL No.:MFCD12469916 MF:C13H9F4NO MW:271.2103
4-(2,5-Dichlorophenoxy)-3-fluoroaniline Catalog No.:AA01A7IO CAS No.:1039869-08-3 MDL No.:MFCD11193294 MF:C12H8Cl2FNO MW:272.1024	N-benzyl-2-cyano-N-ethylacetamide Catalog No.:AA01B1ME CAS No.:1039869-28-7 MDL No.:MFCD11195405 MF:C12H14N2O MW:202.2524
2,3-Dimethyl-1h-indole-7-carbaldehyde Catalog No.:AA007WS5 CAS No.:103987-28-6 MDL No.:MFCD08059725 MF:C11H11NO MW:173.2111	5-Ethynylquinoline Catalog No.:AA0096TN CAS No.:103987-79-7 MDL No.:MFCD07644616 MF:C11H7N MW:153.1800
7-Ethynylquinoline Catalog No.:AA008537 CAS No.:103987-80-0 MDL No.:MFCD18802508 MF:C11H7N MW:153.1800	8-Ethynylquinoline Catalog No.:AA008536 CAS No.:103987-81-1 MDL No.:MFCD16878266 MF:C11H7N MW:153.1800
4-[(E)-(2-Mercapto-4-oxo-1,3-thiazol-5(4h)-ylidene)methyl]benzoic acid Catalog No.:AA007F55 CAS No.:103987-82-2 MDL No.:MFCD01909747 MF:C11H7NO3S2 MW:265.3082	1-Nitro-2-naphthoic acid Catalog No.:AA009SJ8 CAS No.:103987-83-3 MDL No.:MFCD06203335 MF:C11H7NO4 MW:217.1776
1-(3-chloro-2-fluorophenyl)-1H-1,2,3-triazole-4-carboxylic acid Catalog No.:AA01A4PU CAS No.:1039876-00-0 MDL No.:MFCD11192456 MF:C9H5ClFN3O2 MW:241.6063	2-Amino-4-chloro-3-fluorobenzoic acid Catalog No.:AA003A5S CAS No.:1039878-71-1 MDL No.:MFCD11193652 MF:C7H5ClFNO2 MW:189.5715
4-[(4-iodophenyl)amino]butanoic acid Catalog No.:AA01AJSL CAS No.:1039879-15-6 MDL No.:MFCD11194074 MF:C10H12INO2 MW:305.1123	3-(2-Ethylphenyl)-2-propenoic acid Catalog No.:AA008RNJ CAS No.:103988-23-4 MDL No.:MFCD06205460 MF:C11H12O2 MW:176.2118
2,3-dimethyl-2,3-dihydro-1-benzofuran-5-carboxylic acid, Mixture of diastereomers Catalog No.:AA01EL0H CAS No.:103988-32-5 MDL No.:MFCD31616054 MF:C11H12O3 MW:192.2112	4,7-Dimethyl-1H-indole-2-carboxylic acid Catalog No.:AA007F54 CAS No.:103988-96-1 MDL No.:MFCD02664423 MF:C11H11NO2 MW:189.2105
7-chloro-8-fluoro-1,2,3,4-tetrahydroquinoline Catalog No.:AA01C1W5 CAS No.:1039881-41-8 MDL No.:MFCD11192412 MF:C9H9ClFN MW:185.6259	[4-(dimethylamino)-3-nitrophenyl]methanol Catalog No.:AA01A6O4 CAS No.:1039882-00-2 MDL No.:MFCD11191404 MF:C9H12N2O3 MW:196.2032
3-(chloromethyl)-5-(2,3-dichlorophenyl)-1,2,4-oxadiazole Catalog No.:AA01BHUP CAS No.:1039885-60-3 MDL No.:MFCD11189767 MF:C9H5Cl3N2O MW:263.5078	4-(2-methoxy-2-oxoethoxy)-3,5-dimethylbenzoic acid Catalog No.:AA019YPP CAS No.:1039886-43-5 MDL No.:MFCD11188423 MF:C12H14O5 MW:238.2366
6-Ethoxy-1h-indole-2-carboxylic acid Catalog No.:AA008RNH CAS No.:103989-09-9 MDL No.:MFCD02664460 MF:C11H11NO3 MW:205.2099	2-Oxazolidinone, 3-(4-acetylphenyl)- Catalog No.:AA007WS3 CAS No.:103989-12-4 MDL No.:MFCD02946492 MF:C11H11NO3 MW:205.2099
(2-methylnaphthalen-1-yl)boronic acid Catalog No.:AA003HN1 CAS No.:103989-84-0 MDL No.:MFCD03452758 MF:C11H11BO2 MW:186.0148	3-(2-chlorophenoxymethyl)-1-benzofuran-2-carboxylic acid Catalog No.:AA01A9F5 CAS No.:1039891-11-6 MDL No.:MFCD13381158 MF:C16H11ClO4 MW:302.7091
3-[(thiophen-2-ylsulfanyl)methyl]-1-benzofuran-2-carboxylic acid Catalog No.:AA019Y3H CAS No.:1039891-26-3 MDL No.:MFCD12469026 MF:C14H10O3S2 MW:290.3574	(3-Fluoro-4-[4-(pyrimidin-2-yl)piperazin-1-yl]phenyl)methanamine Catalog No.:AA019WRN CAS No.:1039891-92-3 MDL No.:MFCD12913219 MF:C15H18FN5 MW:287.3353
1-[4-(Aminomethyl)-2-fluorophenyl]piperidin-4-ol Catalog No.:AA019VDV CAS No.:1039892-60-8 MDL No.:MFCD11191685 MF:C12H17FN2O MW:224.2746	[4-(4-ethylpiperazin-1-yl)-3-fluorophenyl]methanamine Catalog No.:AA01ABEN CAS No.:1039892-84-6 MDL No.:MFCD11191697 MF:C13H20FN3 MW:237.3164
4-(tert-butoxy)pyridin-3-amine Catalog No.:AA01A1KV CAS No.:1039893-67-8 MDL No.:MFCD11196185 MF:C9H14N2O MW:166.2203	[4-(2,3-dichlorophenoxy)phenyl]methanamine Catalog No.:AA01AKOB CAS No.:1039894-09-1 MDL No.:MFCD11191753 MF:C13H11Cl2NO MW:268.1385
5-[3-(difluoromethoxy)phenyl]-1,3,4-oxadiazol-2-amine Catalog No.:AA01AAD7 CAS No.:1039899-32-5 MDL No.:MFCD11193592 MF:C9H7F2N3O2 MW:227.1676	Methyl cyclohexylphenylglycolate Catalog No.:AA00HA64 CAS No.:10399-13-0 MDL No.:MFCD00269807 MF:C15H20O3 MW:248.3175
Ethyl 5-methoxy-2-nitrobenzoate Catalog No.:AA00HA65 CAS No.:10399-67-4 MDL No.:MFCD12913344 MF:C10H11NO5 MW:225.1980	Benzenemethanamine, a-methyl-4-(1-methylethoxy)- Catalog No.:AA00HA66 CAS No.:103990-05-2 MDL No.:MFCD01732446 MF:C11H17NO MW:179.2588
1-[4-(propan-2-yloxy)phenyl]ethan-1-amine hydrochloride Catalog No.:AA019WYL CAS No.:103990-06-3 MDL No.:MFCD13195934 MF:C11H18ClNO MW:215.7197	1-(2-Fluoro-4-methylphenyl)-1h,4h,5h,6h-cyclopenta[c]pyrazole-3-carboxylic acid Catalog No.:AA01ABGP CAS No.:1039900-17-8 MDL No.:MFCD12559985 MF:C14H13FN2O2 MW:260.2636
6-(tert-butoxy)pyridine-3-carboxylic acid Catalog No.:AA01A4YK CAS No.:1039902-71-0 MDL No.:MFCD11196487 MF:C10H13NO3 MW:195.2151	4-amino-6-chloro-3,4-dihydro-2H-1lambda6-benzothiopyran-1,1-dione Catalog No.:AA019ZRY CAS No.:1039912-70-3 MDL No.:MFCD11190750 MF:C9H10ClNO2S MW:231.6992
(2-ethoxy-5-nitrophenyl)methanol Catalog No.:AA019W5N CAS No.:1039913-30-8 MDL No.:MFCD08460626 MF:C9H11NO4 MW:197.1879	ethyl N-(2-amino-4-bromophenyl)carbamate Catalog No.:AA01A3HZ CAS No.:1039915-77-9 MDL No.:MFCD11198901 MF:C9H11BrN2O2 MW:259.0998
5-(4-propanoylphenoxy)pentanoic acid Catalog No.:AA01AA12 CAS No.:1039915-79-1 MDL No.:MFCD11542180 MF:C14H18O4 MW:250.2903	2-(2,2,3,3-tetrafluoropropoxy)acetonitrile Catalog No.:AA01BDFU CAS No.:1039916-10-3 MDL No.:MFCD11197534 MF:C5H5F4NO MW:171.0929
2-(heptyloxy)propanoic acid Catalog No.:AA00IX09 CAS No.:1039920-80-3 MDL No.:MFCD05669780 MF:C10H20O3 MW:188.2640	3-{[(4-hydroxypyrimidin-2-yl)sulfanyl]methyl}-1-benzofuran-2-carboxylic acid Catalog No.:AA019Y12 CAS No.:1039922-41-2 MDL No.:MFCD13383585 MF:C14H10N2O4S MW:302.3052
3-Amino-1-[2-(propan-2-yl)phenyl]thiourea Catalog No.:AA01A9QF CAS No.:1039924-20-3 MDL No.:MFCD11188561 MF:C10H15N3S MW:209.3112	4-(difluoromethoxy)-3,5-dimethylbenzoic acid Catalog No.:AA01AGKQ CAS No.:1039927-58-6 MDL No.:MFCD11193519 MF:C10H10F2O3 MW:216.1814
4-(1H-1,2,4-Triazol-1-yl)butan-2-amine Catalog No.:AA019Y89 CAS No.:1039928-99-8 MDL No.:MFCD11188799 MF:C6H12N4 MW:140.1863	2-{[(2-methylbutan-2-yl)oxy]methyl}aniline Catalog No.:AA01A6UB CAS No.:1039930-62-5 MDL No.:MFCD11196370 MF:C12H19NO MW:193.2854
[2-(cyclopropylmethoxy)phenyl]methanol Catalog No.:AA019X6T CAS No.:1039931-23-1 MDL No.:MFCD11190320 MF:C11H14O2 MW:178.2277	1-(2,6-dichlorophenyl)cyclopropane-1-carboxylic acid Catalog No.:AA019ZOA CAS No.:1039931-24-2 MDL No.:MFCD11036987 MF:C10H8Cl2O2 MW:231.0753
1-(2-methylphenyl)cyclohexane-1-carboxylic acid Catalog No.:AA01A8GU CAS No.:1039931-32-2 MDL No.:MFCD11037175 MF:C14H18O2 MW:218.2915	1-(4-bromophenyl)cycloheptane-1-carboxylic acid Catalog No.:AA01B8IR CAS No.:1039931-40-2 MDL No.:MFCD11188901 MF:C14H17BrO2 MW:297.1876
3-Phenoxycyclobutanecarboxylic acid Catalog No.:AA008UBO CAS No.:1039931-72-0 MDL No.:MFCD11188908 MF:C13H16O4 MW:236.2637	[1-(4-Bromophenyl)cyclobutyl]methanamine Catalog No.:AA00921B CAS No.:1039932-36-9 MDL No.:MFCD11188929 MF:C11H14BrN MW:240.1396
{1-[3-(trifluoromethyl)phenyl]cyclobutyl}methanamine Catalog No.:AA019QRF CAS No.:1039932-76-7 MDL No.:MFCD11188948 MF:C12H14F3N MW:229.2415	3-[(octyloxy)methyl]aniline Catalog No.:AA019XS2 CAS No.:1039933-71-5 MDL No.:MFCD11196400 MF:C15H25NO MW:235.3651
5-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-1,3,4-oxadiazol-2-amine Catalog No.:AA018GBK CAS No.:1039933-90-8 MDL No.:MFCD11188981 MF:C10H9N3O3 MW:219.1968	3,3,4,4-tetrafluorobutanoic acid Catalog No.:AA01BTWB CAS No.:1039939-83-7 MDL No.:MFCD30333852 MF:C4H4F4O2 MW:160.0670
2-Bromo-4,5-difluorobenzoyl chloride Catalog No.:AA008XJ5 CAS No.:103994-89-4 MDL No.:MFCD07368698 MF:C7H2BrClF2O MW:255.4440	5-(But-3-en-1-yloxy)pentanoic acid Catalog No.:AA01A4MN CAS No.:1039945-25-9 MDL No.:MFCD11197689 MF:C9H16O3 MW:172.2215
3-[(tert-butoxy)methyl]aniline Catalog No.:AA01B9LM CAS No.:1039946-12-7 MDL No.:MFCD11196310 MF:C11H17NO MW:179.2588	1-(4-chloro-2-fluorophenyl)-2-(pyridin-2-yl)ethan-1-one Catalog No.:AA01B1L1 CAS No.:1039946-66-1 MDL No.:MFCD11188621 MF:C13H9ClFNO MW:249.6681
3-([(4-Methylpentyl)oxy]methyl)aniline Catalog No.:AA019XUJ CAS No.:1039947-92-6 MDL No.:MFCD11196364 MF:C13H21NO MW:207.3119	4-(2-phenylethoxy)butan-1-amine Catalog No.:AA019VEG CAS No.:1039949-96-6 MDL No.:MFCD11196472 MF:C12H19NO MW:193.2854
2-(tert-Butoxy)pyridine-4-carboxylic acid Catalog No.:AA01A3U8 CAS No.:1039950-66-7 MDL No.:MFCD11196483 MF:C10H13NO3 MW:195.2151	1-(2,6-dichlorophenyl)cyclobutane-1-carboxylic acid Catalog No.:AA01BECO CAS No.:1039951-74-0 MDL No.:MFCD11037041 MF:C11H10Cl2O2 MW:245.1019
1-(2,4-dichlorophenyl)cyclohexane-1-carboxylic acid Catalog No.:AA01C3TM CAS No.:1039952-20-9 MDL No.:MFCD11037151 MF:C13H14Cl2O2 MW:273.1551	1-[1-(pyridin-4-yl)ethyl]piperidin-4-amine Catalog No.:AA01A1LH CAS No.:1039952-75-4 MDL No.:MFCD11199036 MF:C12H19N3 MW:205.2994
(5-fluoro-2-methoxyphenyl)(3-methoxyphenyl)methanamine Catalog No.:AA019TBP CAS No.:1039960-60-5 MDL No.:MFCD12532916 MF:C15H16FNO2 MW:261.2914	2-Hydrazinylethane-1-sulfonamide Catalog No.:AA01AIHP CAS No.:1039961-64-2 MDL No.:MFCD11191982 MF:C2H9N3O2S MW:139.1768
4-chloro-1-[4-(chloromethyl)phenoxy]-2-methylbenzene Catalog No.:AA01AIKH CAS No.:1039962-36-1 MDL No.:MFCD11190733 MF:C14H12Cl2O MW:267.1505	ethyl 1-(2-aminobenzoyl)piperidine-3-carboxylate Catalog No.:AA00IRRH CAS No.:1039964-65-2 MDL No.:MFCD12560018 MF:C15H20N2O3 MW:276.3309
3-{[(2-chlorophenyl)sulfanyl]methyl}-1-benzofuran-2-carboxylic acid Catalog No.:AA019Y0Z CAS No.:1039967-31-1 MDL No.:MFCD13378784 MF:C16H11ClO3S MW:318.7747	5-(1-chloroethyl)-3-(thiophen-2-yl)-1,2,4-oxadiazole Catalog No.:AA019LJB CAS No.:1039967-49-1 MDL No.:MFCD09971553 MF:C8H7ClN2OS MW:214.6720
5-Chloro-6-oxo-1,6-dihydropyridine-2-carboxylic acid Catalog No.:AA008Z1P CAS No.:103997-21-3 MDL No.:MFCD19687157 MF:C6H4ClNO3 MW:173.5539	5-Chloro-6-methylpyridin-2-ol Catalog No.:AA007WQD CAS No.:103997-23-5 MDL No.:MFCD16610477 MF:C6H6ClNO MW:143.5709
3-Amino-n-(5-bromopyridin-2-yl)benzamide Catalog No.:AA01A8KA CAS No.:1039972-12-7 MDL No.:MFCD11184844 MF:C12H10BrN3O MW:292.1313	1-(Carbamoylmethyl)-1h-1,3-benzodiazole-5-carboxylic acid Catalog No.:AA019UUR CAS No.:1039976-04-9 MDL No.:MFCD11125333 MF:C10H9N3O3 MW:219.1968
1-benzyl-N-(prop-2-en-1-yl)pyrrolidin-3-amine Catalog No.:AA01AGG0 CAS No.:1039980-58-9 MDL No.:MFCD11183217 MF:C14H20N2 MW:216.3220	2-Amino-3-fluoro-6-methylbenzoic acid Catalog No.:AA009813 CAS No.:1039981-89-9 MDL No.:MFCD11183541 MF:C8H8FNO2 MW:169.1530
1-Methyl-4-phenyl-1h-imidazol-5-amine Catalog No.:AA008V3Q CAS No.:1039984-25-2 MDL No.:MFCD11186826 MF:C10H11N3 MW:173.2144	6-chloro-1-N-(propan-2-yl)benzene-1,2-diamine Catalog No.:AA019VCF CAS No.:1039985-85-7 MDL No.:MFCD11186903 MF:C9H13ClN2 MW:184.6659
N4-(2-methoxyethyl)pyridine-3,4-diamine Catalog No.:AA01AM2M CAS No.:1039985-93-7 MDL No.:MFCD11186908 MF:C8H13N3O MW:167.2083	N4-(pentan-3-yl)pyridine-3,4-diamine Catalog No.:AA01AL6X CAS No.:1039986-25-8 MDL No.:MFCD11186932 MF:C10H17N3 MW:179.2621
2-Chloro-n-(2-fluoro-4-methylphenyl)propanamide Catalog No.:AA019KN7 CAS No.:1039986-34-9 MDL No.:MFCD11183594 MF:C10H11ClFNO MW:215.6518	3-(1-aminoethyl)-N,N-dimethylbenzene-1-sulfonamide Catalog No.:AA01A9YH CAS No.:1039986-64-5 MDL No.:MFCD11123050 MF:C10H16N2O2S MW:228.3112