955978-75-3

Upstream product

• 955978-77-5 N-[3-bromo-2-(bromomethyl)phenyl]-2,2,2-trifluoroacetamide 
• 955978-76-4 N-(3-bromo-2-methylphenyl)-2,2,2-trifluoroacetamide 
• 55289-36-6 3-bromo-2-methylaniline 
• 55289-35-5 2-bromo-6-nitrotoluene 

Relevant academic research and scientific papers

Two-step, regioselective, multigram-scale synthesis of 2-(trifluoromethyl)indoles from 2-nitrotoluenes

The acylation of 2-nitrotoluenes using ethyl trifluoroacetate, one of the least expensive sources of a trifluoromethyl group, produces intermediate 2-nitrobenzyl trifluoromethyl ketones which, without the need for isolation, are cyclized under the action of Zn/AcOH providing 2-(trifluoromethyl)indoles unsubstituted at the C3 position. The developed method avoids the use of expensive catalysts and harsh reaction conditions. The method is readily scalable without a significant decrease in performance upon going from 10- to 250-mmol scale.

INDOLE AND BENZIMIDAZOLE DERIVATIVES AS DUAL 5-HT2A AND 5-HT6 RECEPTOR ANTAGONISTS

The invention relates to new 4-(piperazin-1-yl)-2-(trifluoromethyl)-1H-indoles and 4-(piperazin-1-yl)-2-(trifluoromethyl)-1H-benzimidazoles represented by formula (I), wherein all symbols and variables are as defined in the description. The compounds can find use in a method of prevention and/or treatment of diseases selected from the group consisting of Alzheimer's disease, Parkinson's disease, Levy body dementia, dementia-related psychosis, schizophrenia, delusional syndromes and other psychotic conditions related and not related to taking psychoactive substances, depression, anxiety disorders of various aetiology, sleep disorders of various aetiology.

THIENOPYRIMIDIENE DERIVATIVES AS PI3K INHIBITORS

Thienopyrimidines of formula (I) wherein W and R1 to R4 are as defined in the claims, and the pharmaceutically acceptable salts thereof are inhibitors of PI3K and are selective for the p110δ isoform, which is a class Ia PI3 kinase, over both other class Ia and class Ib kinases. The compounds may be used to treat diseases and disorders arising from abnormal cell growth, function or behaviour associated with PI3 kinase such as cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine function disorders and neurological disorders.

2-MORPHOLIN-4-YL-PYRIMIDINES AS PI3K INHIBITORS

The invention provides compounds which are pyrimidines of formula (I) wherein R1 is a group -NR-(CHR)m-X; R2 is a substituted indolyl group; R is H or C1-C6 alkyl; m is 1, 2, 3 or 4; and X is a pyridyl ring; and the pharmaceutically acceptable salts thereof. These compounds are inhibitors of PI3K and may thus be used to treat diseases and disorders arising from abnormal cell growth, function or behaviour associated with PI3 kinase such as cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine function disorders and neurological disorders.

PHARMACEUTICAL COMPOUNDS

Furanopyrimidines of formula (I): wherein W represents a furan ring; R1 and R2 form, together with the N atom to which they are attached, a group of the following formula (IIa): in which A is selected from: (a) a 4- to 7-membered saturated N-containing heterocyclic ring which includes 0 or 1 additional heteroatoms selected from N, S and O, the ring being fused to a second ring selected from a 4- to 7-membered saturated N-containing heterocyclic ring as defined above, a 5- to 12-membered unsaturated heterocyclic ring, a 5- to 7-membered saturated O-containing heterocyclic ring, a 3- to 12- membered saturated carbocyclic ring and an unsaturated 5- to 12- membered carbocyclic ring to form a heteropolycyclic ring system, the heteropolycyclic ring system being unsubstituted or substituted; (b) a 4- to 7-membered saturated N-containing heterocyclic ring which includes 0 or 1 additional heteroatoms selected from N, S and O and which further comprises, linking two constituent atoms of the ring, a bridgehead group selected from -(CR'2)n- and -(CR'2)r-O-(CR'2)s- wherein each R' is independently H or C1 - C6 alkyl, n is 1, 2 or 3, r is 0 or 1 and s is 0 or 1, the remaining ring positions being unsubstituted or substituted; and (c) a group of formula (IIb): wherein ring B is a 4- to 7-membered saturated N-containing heterocyclic ring which includes 0 or 1 additional heteroatoms selected from N, S and O and ring B' is a 3- to 12- membered saturated carbocyclic ring, a 5- to 7- membered saturated O-containing heterocyclic ring or a 4- to 7-membered saturated N-containing heterocyclic ring as defined above, each of B and B' being unsubstituted or substituted; m is 0, 1 or 2; R3 is H or C1-C6 alkyl; R4 is an indole group which is unsubstituted or substituted; and Ra is selected from R, halo, CN, C(O)NR2, halo(C1-C6)alkyl, SO2R, SO2NR2, NRSO2R, NRC(O)R, NRC(O)OR and NRC(O)NR2 wherein each R is independently H or C1-C6 alkyl; and the pharmaceutically acceptable salts thereof are inhibitors of PI3K and are selective for the p110δ isoform, which is a class Ia PI3 kinase, over both other class Ia and class Ib kinases. The compounds may be used to treat diseases and disorders arising from abnormal cell growth, function or behaviour associated with PI3 kinase such as cancer, immune disorders, cardiovascular disease, viral infection, inflammation, metabolism/endocrine function disorders and neurological disorders.

PYRIMIDINE DERIVATIVES AS PI3K INHIBITORS

Thienopyrimidines of formula (Ia) or (Ib): wherein R1, R2, R3, are as defined in the claims.