Product Master List

LCC Product Master List – Technical Overview

LCC Product Master List - Scaffolds

Figure 1 A) Mono-substituted and B) di-substituted N-heterocyclic scaffolds. C) Carbocyclic scaffolds. D) Representative fused, spiro and bridged compounds

The Product Master List comprises of highly diverse fragments, scaffolds and building blocks that are accessible using LCC’s chemical technologies and expertise in catalysis and asymmetric synthesis. The library has been developed to meet the needs of functionalised, sp3-rich chemicals that can effectively explore new chemical space. The library has been designed based on 10 N-heterocyclic and 4 carbocyclic scaffolds that LCC have extensive experience to synthesise (Fig. 1). Fused, spiro and bridged (hetero)cycles were also included to cover conformationally-restricted and strained scaffolds. Hence, the high sp3-fraction and increased cover age of 3D chemical space are a result of a rational design process.

Additional steps were taken to further optimise drug-like properties:

  • a) covalent warheads and Pan-assay interference compounds (PAINS) compounds were excluded and
  • b) a large set of fluorinated compounds has been included to modulate basicity (including CH2F, CHF2 and CF3 substituted compounds).


Mono-substituted N-heterocycles were designed after selection of appropriate protecting groups (R1) and substituents (R2). Each compound can be provided as pure R or S enantiomer or racemate (Fig. 2) R1 comprises Boc, Fmoc, HCl salt and H (free base). Compounds bearing customised protecting groups (Bn, R-SO2, …) can be provided on request.


              R1
R2

Free base
Boc
Fmoc
HCI
Racemate
R




S




Figure 2: 12 available forms of each compound type.

Representative structures are:


R2 = COOH/R, Me, CH2OH/TBDMS, CH2NH2/NHBoc, CH2CH2OH/TBDMS, CH2CH2NH2/NHBoc, CONH2, OH/TBDMS, CH2F, CF3, OH/TBDMS, NH2, NMe2, NHMe, NMeBoc, NHAc.

R2 = F, Cl, Br, I, CN, OMe, NH2/Boc, NHMe, NMeBoc, NHAc, CO2H/R, CONH2, CHO, CH2OH, CH2OTBDMS, CH2CH2OH, CH2CH2OTBDMS.

R2 = COOH/R, Me, CH2OH/TBDMS, CH2NH2/NHBoc, CH2CH2OH/TBDMS, CH2CH2NH2/NHBoc, CONH2, OH/TBDMS, CH2F, CF3, OH/TBDMS, NH2, NMe2, NHMe, NMeBoc, NHAc.

When more than one amino group is present, mono-protected and orthogonally protected forms are available (upon request if not in the catalogue).

The extensive expertise of LCC in synthesising chiral N-heterocycles has allowed the design of di-substituted N-heterocycles and carbocycles. These compounds are available as pure enantiomers or racemic cis or trans. The endocyclic nitrogen can be Boc- or Fmoc-protected, free base or HCl salt (Fig. 1B-C).

     R1
R’,R”
Free base
Boc
Fmoc
HCI
Rac-cis
Rac-trans




(R,R)




(R,S)




(S,R)




(S,S)




R’/R” pairs were specially selected for various applications, such as:

  • a) fragments for FBLD
  • b) scaffolds and building blocks for HTS library synthesis (including DEL’s).

Available R’/R” pairs:

              R'
R”
F
NH2OH
Ar
CO2H
Me
F



NH2





OH






Ar






CO2H





Me






Ar = phenyl or Ar-X where X = F, Cl, Br, I (ortho, meta and para).

Substitution patterns: 2,3-substituted azetidines; 2,3-substituted, 2,4-substituted and 3,4-substituted pyrrolidines; 2,3-substituted, 2,4-substituted 2,5-substituted and 3,4-substituted piperidines.

For a copy of the full library, or a customised sub-library based on your specific application requirements, please contact our BD Director, Dr Joanne Johnson:
joanne.johnson@liverpoolchirochem.com