Compounds from DNDi imidazopyridine collection

[bendndi]

Hi all,
As discussed in the meeting last week with @mattodd and others, I've trawled through the DNDi collection of imidazopyridines and pulled the following compounds up as being a) diverse representation and b) probably available for test. Is 30 compounds too many? If so, help me whittle down the ones to test. Note that most if not all are at least 2 jumps away from the hit, and it's therefore unlikely any will be active. But it could be good to test, because if one is active it'll give a new avenue.

Compounds will be shipped from one of three location but can be at UCL relatively painlessly ( they will be coming from Imperial, Northeastern or TCG LS in Kolkata).

[danaklug]

Hi Ben, thanks so much for this! We are happy to receive as many of these compounds at UCL as possible and get them tested for MRSA activity. It looks like we should be able to make some analogues that bridge the SAR between this series and ours if any of them turn out to be active.

Our shipping address can be found here and we would prefer at least 2 mg of solid compound (If any are in solution I can contact Paul and ask about amount/concentration/etc). I'll plan on doing a low-res MS as QC and can add them to our OSA molecule spreadsheet as well.

[bendndi]

@danaklug No worries, will look into shipping asap. You can run MS if you like but all componuds have NMR & LCMS data already available.

[bendndi]

@danaklug Wheels in motion to get these shipped to you from Imperial, Northeastern and TCG. Will keep you posted.

[danaklug]

@bendndi Amazing, thanks!

[MFernflower]

Great stuff Ben!

[danaklug]

Update: Compounds from TGC have been received.

@bendndi Just wondering if you have a spreadsheet with SMILES for these compounds so I can add them to the master OSA sheet?

[bendndi]

@danaklug

ENTITY_ID_1	BATCH_ID_1	SMILES	BATCH_TAG_ID_1
DNDI0003363575	PCWUX02-1826	COc1ccn2c(Nc3ccc(F)cn3)c(nc2c1)c4ccccn4	EW2282-932-P1
DNDI0003148395	PCWUX02-1745	CN(C)c1ccc(cc1)c2nc3cc(C)ccn3c2NC4CCCC4	EW614-744-P1
DNDI0003083531	PCWUX02-1747	Cc1ccc2nc(c(Nc3ccc4OCCOc4c3)n2c1)c5ccccn5	EW2282-742-P1
DNDI0003297854	PCWUX02-1761	Cc1ccc2nc(c(NCc3ccccc3)n2c1)c4ccccn4	EW1687-1491-P1
DNDI0003365536	PCWUX02-1878	COc1ccn2c(Nc3cccc(F)c3)c(nc2c1)c4cscn4	EW7785-64-P1
DNDI0003364483	PCWUX02-1840	CN(C)Cc1ccc2nc(c(Nc3cccc(F)c3)n2c1)c4ccccn4	EW2282-958-P1
DNDI0003297119	PCWUX02-1805	C1CCC(C1)Nc2c(nc3ccccn23)c4nccs4	EW614-757-P1
DNDI0003297857	PCWUX02-1769	CN(C)c1ccc(cc1)c2nc3cc(C)ccn3c2Nc4ccc(F)cc4	EW2282-807-P1
DNDI0003297870	PCWUX02-1798	Fc1ccc(Nc2c(nc3ccccn23)c4nccs4)cc1	EW1687-1477-P1
DNDI0003297115	PCWUX02-1797	Cn1ccnc1c2nc3ccccn3c2Nc4ccc(F)cc4	EW1687-1451-P1
DNDI0003364493	PCWUX02-1864	COc1ccn2c(Nc3cccc(F)c3)c(nc2c1)c4cn(C)cn4	EW7785-36-P1
DNDI0003365541	PCWUX02-1845	Fc1cccc(Nc2c(nc3CCCCn23)c4ccccn4)c1	EW2282-1088-P1
DNDI0003083431	PCWUX02-1744	COc1ccc(cc1OC)c2nc3ccc(C)cn3c2NCc4occc4	EW614-718-P1
DNDI0003364484	PCWUX02-1847	COc1ccn2c(N3CCOCC3)c(nc2c1)c4ccccn4	EW6351-349-P1
DNDI0003363569	PCWUX02-1791	C1CN(CCO1)c2c(nc3ccccn23)c4ccccn4	EW2282-893-P1
DNDI0003363573	PCWUX02-1824	COc1ccn2c(Nc3ccccc3F)c(nc2c1)c4ccccn4	EW2282-926-P1
DNDI0003365537	PCWUX02-1838	COCc1ccc2nc(c(Nc3cccc(F)c3)n2c1)c4ccccn4	EW2282-1032-P1
DNDI0003365539	PCWUX02-1831	COc1ccn2c(NCc3cn(C)cn3)c(nc2c1)c4ccccn4	EW2282-1082-P1
DNDI0003364477	PCWUX02-1827	COc1ccn2c(Nc3ccnc(C)c3)c(nc2c1)c4ccccn4	EW2282-933-P1

[bendndi]

@danaklug here is the same info for the componuds coming from Northeastern and Imperial:

Compound ID	Batch Tag	SMILES	Batch ID
DNDI0003389102	OSNImperial-xzw025	COc1ccn2c(Nc3ccc4OCCOc4c3)c(nc2c1)c5c[nH]cn5	PCOSNIMP2-015
DNDI0003389103	OSNImperial-xzw026	COc1ccc2nc(c(Nc3ccc4OCCOc4c3)n2c1)c5c[nH]cn5	PCOSNIMP2-016
DNDI0003388148	NEU-0005941=AA-001	CC(C)Nc1c(nc2cnccn12)c3ccccn3	PCOSNNEUP2-009
DNDI0003515912	NEU-AQ-1-047-04	COc1ccn2c(Nc3ccccc3F)c(nc2c1)c4cnn(C)c4	PCOSNNEUP2-026
DNDI0003517000	NEU-0006414=AA-001=D	COc1ccn2cc(nc2c1)c3ccccn3	PCOSNNEUP2-028
DNDI0003517002	NEU-0006416=AA-001=D	COc1ccn2c(c3cccc(Cl)n3)c(nc2c1)c4ccccn4	PCOSNNEUP2-030
DNDI0003578427	NEU-0006454=AA-001=D	COc1ccn2c(c3ccc(F)cc3)c(nc2c1)c4ccccn4	PCOSNNEUP2-033
DNDI0003578436	NEU-0006463=AA-001=D	Fc1ccc(cc1)c2c(nc3ccccn23)c4ccccn4	PCOSNNEUP2-042
DNDI0003578712	NEU-0006496=AA-001=D	COc1ccn2c(c3ccccc3)c(nc2c1)c4ccccn4	PCOSNNEUP2-054

[bendndi]

@danaklug and here is some ADME data for some of the componuds:

Compound ID	CHEMISTRY	CLint in vitro hamster mic uL/min/mg.pr	CLint in vitro mouse min  uL/min/mg.pr	CLint in vitro human mic uL/min/mg.pr	CLint in vitro rat hepatocytes uL/min/10e6 cells	K Solub pH7.4 ug/mL	K Solub pH2 ug/mL	K Solub pH2 uM	PPB Human
DNDI0003389102	PCOSNIMP2-015
DNDI0003389103	PCOSNIMP2-016
DNDI0003388148	PCOSNNEUP2-009			248	101			680.9	78
DNDI0003515912	PCOSNNEUP2-026			3	82.3
DNDI0003517000	PCOSNNEUP2-028			300	52.9				79
DNDI0003517002	PCOSNNEUP2-030			124	12.9				96.5
DNDI0003578427	PCOSNNEUP2-033
DNDI0003578436	PCOSNNEUP2-042
DNDI0003578712	PCOSNNEUP2-054			224	23.9				97.2
DNDI0003083431	PCWUX02-1744	2897	1006	257.5		41.08	79.97
DNDI0003148395	PCWUX02-1745	1991	1295	188		0.33	66.89
DNDI0003083531	PCWUX02-1747	2047	410.8	95		8.35	71.68
DNDI0003297854	PCWUX02-1761		1418
DNDI0003297857	PCWUX02-1769
DNDI0003363569	PCWUX02-1791
DNDI0003297115	PCWUX02-1797
DNDI0003297870	PCWUX02-1798
DNDI0003297119	PCWUX02-1805
DNDI0003363573	PCWUX02-1824		133.3
DNDI0003363575	PCWUX02-1826	306	80.75	35.25		76.27	76.27
DNDI0003364477	PCWUX02-1827
DNDI0003365539	PCWUX02-1831
DNDI0003365537	PCWUX02-1838
DNDI0003364483	PCWUX02-1840
DNDI0003365541	PCWUX02-1845
DNDI0003364484	PCWUX02-1847		137
DNDI0003364493	PCWUX02-1864		11.95
DNDI0003365536	PCWUX02-1878

[danaklug]

Awesome, thanks @bendndi! We'll add all this to the master sheet.

[MFernflower]

@danaklug I assume these will be going straight into the MRSA assay? @bendndi I assume they have been checked for any signs of degradation?

[danaklug]

NEU compounds have arrived as well!

[danaklug]

All compounds from DNDi have now been delivered and will be tested against MRSA in the next round of screening. (They have also all been added to the OSA master sheet with DNDi numbers as vendor ID.)

[edwintse]

UPDATE: The purity of compounds DNDI0003389102 (OSA_000866) and DNDI0003389103 (OSA_000867) are questionable and the biological results are to be excluded.