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27th April 2015 @ 12:47

Dr Mrinalkanti Kundu, Associate Director TCG Lifesciences, India, wrote to the OSM email address with some new suggestions on which molecules to make next. These suggestions have been adapted from the Christmas Top 10 list as well as all the SAR data on the wiki.

Series 4 Suggestions from Mrinal

Thank you Mrinal! The structures are in the attached PDF and image file. Discussion can happen below (just sign in via Google) or on the G+ community or by starting an Issue on Github. Any comments/suggestions, please go ahead - Mrinal is also monitoring these channels. Ought these to be included in the next round of synthesis, or should they perhaps replace any of the compounds listed in the Christmas Top 10?

 

(This post authored by Mat)

Strings:

MK-001: N1=CC2=NN=C(N2C(=C1)OC[C@H](c1cc(c(cc1)F)F)OC)c1cnc(cc1)C#N
MK-002: N1=CC2=NN=C(N2C(=C1)OC[C@H](c1cc(c(cc1)F)F)OC(F)F)c1cnc(cc1)C#N
MK-003: N1=CC2=NN=C(N2C(=C1)OC[C@H](c1cc(c(cc1)F)F)OC)c1ccc(cc1)Cl
MK-004: N1=CC2=NN=C(N2C(=C1)OC[C@H](c1ccccc1Cl)OC)c1ccc(cc1)C#N
MK-005: N1=CC2=NN=C(N2C(=C1)OC[C@H](c1cc(cc(c1)F)F)OC)c1ccc(cc1)C#N
MK-006: N1=CC2=NN=C(N2C(=C1)OC[C@H](c1cc(ncc1)C(F)(F)F)OC)c1ccc(cc1)Cl
MK-007: N1=CC2=NN=C(N2C(=C1)OCCc1cc(ncc1)C(F)(F)F)c1ccc(cc1)Cl
MK-008: O(c1ccc(cc1)C1=NN=C2N1C(=CN=C2)OC[C@H](c1cc(ncc1)C(F)(F)F)OC)C(F)F
MK-009: O(c1ccc(cc1)C1=NN=C2N1C(=CN=C2)OCCc1cc(ncc1)C(F)(F)F)C(F)F
MK-010: O([C@H](c1cc(ncc1)C(F)(F)F)COC1=CN=CC2=NN=C(N12)c1ccc(cc1)C#N)C
MK-011: O([C@H](c1cc(ncc1)C(F)(F)F)COC1=CN=CC2=NN=C(N12)c1ccc(cc1)C#N)C(F)F
MK-012: N1=CC2=NN=C(N2C(=C1)OCCc1cc(ncc1)C(F)(F)F)c1ccc(cc1)C#N

MK-001: 1/C20H14F2N6O2/c1-29-17(12-3-5-15(21)16(22)6-12)11-30-19-10-24-9-18-26-27-20(28(18)19)13-2-4-14(7-23)25-8-13/h2-6,8-10,17H,11H2,1H3/t17-/m0/s1

MK-002: 1/C20H12F4N6O2/c21-14-4-2-11(5-15(14)22)16(32-20(23)24)10-31-18-9-26-8-17-28-29-19(30(17)18)12-1-3-13(6-25)27-7-12/h1-5,7-9,16,20H,10H2/t16-/m0/s1

MK-003: 1/C20H15ClF2N4O2/c1-28-17(13-4-7-15(22)16(23)8-13)11-29-19-10-24-9-18-25-26-20(27(18)19)12-2-5-14(21)6-3-12/h2-10,17H,11H2,1H3/t17-/m0/s1

MK-004: 1/C21H16ClN5O2/c1-28-18(16-4-2-3-5-17(16)22)13-29-20-12-24-11-19-25-26-21(27(19)20)15-8-6-14(10-23)7-9-15/h2-9,11-12,18H,13H2,1H3/t18-/m0/s1

MK-005: 1/C21H15F2N5O2/c1-29-18(15-6-16(22)8-17(23)7-15)12-30-20-11-25-10-19-26-27-21(28(19)20)14-4-2-13(9-24)3-5-14/h2-8,10-11,18H,12H2,1H3/t18-/m0/s1

MK-006: 1/C20H15ClF3N5O2/c1-30-15(13-6-7-26-16(8-13)20(22,23)24)11-31-18-10-25-9-17-27-28-19(29(17)18)12-2-4-14(21)5-3-12/h2-10,15H,11H2,1H3/t15-/m0/s1

MK-007: 1/C19H13ClF3N5O/c20-14-3-1-13(2-4-14)18-27-26-16-10-24-11-17(28(16)18)29-8-6-12-5-7-25-15(9-12)19(21,22)23/h1-5,7,9-11H,6,8H2

MK-008: 1/C21H16F5N5O3/c1-32-15(13-6-7-28-16(8-13)21(24,25)26)11-33-18-10-27-9-17-29-30-19(31(17)18)12-2-4-14(5-3-12)34-20(22)23/h2-10,15,20H,11H2,1H3/t15-/m0/s1

MK-009: 1/C20H14F5N5O2/c21-19(22)32-14-3-1-13(2-4-14)18-29-28-16-10-26-11-17(30(16)18)31-8-6-12-5-7-27-15(9-12)20(23,24)25/h1-5,7,9-11,19H,6,8H2

MK-010: 1/C21H15F3N6O2/c1-31-16(15-6-7-27-17(8-15)21(22,23)24)12-32-19-11-26-10-18-28-29-20(30(18)19)14-4-2-13(9-25)3-5-14/h2-8,10-11,16H,12H2,1H3/t16-/m0/s1

MK-011: 1/C21H13F5N6O2/c22-20(23)34-15(14-5-6-29-16(7-14)21(24,25)26)11-33-18-10-28-9-17-30-31-19(32(17)18)13-3-1-12(8-27)2-4-13/h1-7,9-10,15,20H,11H2/t15-/m0/s1

MK-012: 1/C20H13F3N6O/c21-20(22,23)16-9-13(5-7-26-16)6-8-30-18-12-25-11-17-27-28-19(29(17)18)15-3-1-14(10-24)2-4-15/h1-5,7,9,11-12H,6,8H2

Attached Files
16th April 2015 @ 00:36

One of the key issues to solve in open source drug discovery and development programs is how to obtain physical samples of molecules for evaluation. A number of different methods can be envisaged, ranging from direct funding of synthesis (e.g. from grant money, hiring local researchers) through student classes to individual pro bono contributions from academia or industry. A possibility we’d like to build with community help this year is the Molecular Craigslist. We were speaking with Assay Depot about this idea - CEO Kevin Lustig has for a long time been pioneering new ways to source inputs for research projects.

But what about direct purchase of compounds from contract research organizations (CROs)? I believe that such an approach is gaining in popularity with NGOs requiring rapid synthesis of small molecules as part of in-house or sponsored projects. To get a feel for the commercial cost of single inputs to open source research projects (where the data are needed along with the compound) I decided to run one molecule, required by OSM, through Assay Depot’s suite of synthetic chemistry contract research organizations. The requirements we listed were for a few mg of the sample suitable for biological evaluation, plus all the preparative and characterization data obtained during the molecule’s preparation. There is ample synthetic precedence for the compounds in this series, but the specific analog requested (below) contains an oxetane, representing a not-completely-trivial extension of that methodology.

 

OSM Compounds Requested via Assay Depot



While we agreed not to share details of the companies providing quotations for this request, we can provide the figures quoted. I will be gradually assembling those over on Github so we can decide whether to go ahead with one of the quotes and to what extent this represents a general solution for analog synthesis for cases where we have already established precedence for the methodology.

 

 

OC(C1=CC=CC=C1)COC2=CN=CC3=NN=C(C4COC4)N32

InChI=1S/C16H16N4O3/c21-13(11-4-2-1-3-5-11)10-23-15-7-17-6-14-18-19-16(20(14)15)12-8-22-9-12/h1-7,12-13,21H,8-10H2

ZLHKTQHFEDMDIZ-UHFFFAOYSA-N

Attached Files