251980-67-3

Upstream product

• 2979-19-3 3,3-dimethylcyclohexanone 
• 68-12-2 N,N-dimethyl-formamide 

Downstream Products

• 1228837-05-5 4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-carbaldehyde 
• 1628047-87-9 1-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine hydrogen chloride 
• 1628047-87-9 1-((2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl)methyl)piperazine hydrogenchloride 
• 1228780-71-9 tert-butyl 4-((4′-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1′-biphenyl]-2-yl)methyl)piperazine-1-carboxylate 

Relevant academic research and scientific papers

CONDENSED HETEROCYCLES AS BCL-2 INHIBITORS

The disclosure includes compounds of Formula (A) wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11, h, j, m, n, k, v, s, g, V, W, L, Z1 Q1, Q2, Q3, Q4, Q5, Q6, and Q7, are defined herein. Also disclosed is a method for treating a neoplastic disease, an autoimmune disease, or a neorodegenerative disease with these compounds.

1H-PYRROLO[2,3-B]PYRIDINE DERIVATIVES AS BCL-2 INHIBITORS FOR THE TREATMENT OF NEOPLASTIC AND AUTOIMMUNE DISEASES

The present invention relates to lH-pyrrolo[2,3-b]pyridine derivatives and related compounds as BCL-2 inhibitors for treating neoplastic, autoimmune or neurodegenerative diseases. The present description discloses the synthesis and characterisation of exemplary compounds as well as pharmacological data thereof (e.g. pages 162 to 233; examples 1 to 8; table; compound examples cpd-1 to cpd-135; biological examples 1 to 4).

HOT MELT EXTRUDED SOLID DISPERSIONS CONTAINING A BCL2 INHIBITOR

A pro-apoptotic solid dispersion comprises, a Bcl -2 family protein inhibitory compound of Formula A as defined herein, dispersed in a solid matrix that comprises (a) a pharmaceutically acceptable water-soluble polymeric carrier, and (b) a pharmaceutically acceptable surfactant. A process for preparing such a solid dispersion comprises subjecting to elevated temperature the compound of Formula A, the water-soluble polymeric carrier, and the surfactant to provide an extrudable semi-solid mixture; extruding the semi-solid mixture; and cooling the resulting extrudate to provide a solid matrix comprising the polymeric carrier, and the surfactant and having the compound dispersed in essentially non-crystalline form therein. The solid dispersion is suitable for oral administration to a subject in need thereof for treatment of a disease characterized by overexpression of one or more anti-apoptotic Bcl -2 family proteins, for example cancer or an immune or autoimmune disease.

Synthesis of illudalic acid and analogous phosphatase inhibitors

Developing an efficient, concise synthesis of the fungal natural product illudalic acid has been a long-standing challenge, made more pressing by the recent discovery that illudalic acid and analogs are selective phosphatase inhibitors. Syntheses of illudalic acid have become progressively more efficient over the decades yet remain strategically grounded in a 17-step synthesis reported in 1977. Here we validate a two-step process—convergent [4 + 2] benzannulation and one-pot coordinated functional group manipulations—for preparing the key trifunctional pharmacophore of illudalic acid. The modular building blocks are readily available in 2-3 steps, for a longest linear sequence (LLS) of 5 steps to illudalic acid from 3,3-dimethylcyclopentanone. A small collection of analogous indanes and tetralins featuring the same pharmacophore were prepared by a similar route. These compounds potently and selectively inhibit the human leukocyte common antigen-related (LAR) subfamily of protein tyrosine phosphatases (PTPs). Evidence supporting a postulated covalent ligation mechanism is provided herein.

BCL-2 INHIBITORS

The disclosure includes compounds of Formula (A), (A) wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11, h, j, m, n, k, v, s, g, V, W, L, Z1, Q1, Q2, Q3, Q4, Q5, Q6, and Q7, are defined herein. Also disclosed is a method for treating a neoplastic disease, an autoimmune disease, or a neorodegenerative disease with these compounds.

BCL-2 INHIBITORS

The disclosure includes compounds of Formula (I), (I) wherein Z, Q1, Q3, Q4, Q5, Q6, Q7, R0, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, g, k, m, n, s, v, j, L, Z1, and, W are defined herein. Also disclosed is a method for treating a neoplastic disease and autoimmune disease with these compounds.

CONDENSED HETEROCYCLIC DERIVATIVES AS BCL-2 INHIBITORS FOR THE TREATMENT OF NEOPLASTIC DISEASES

The disclosure includes compounds of Formula (A) wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, and R12, j, k, m, n, Y, W, W1, W2, W3, V, L, Z1, Q1, Q2, Q3, and Q4, are defined herein. Also disclosed is a method for treatinga neoplastic disease, an autoimmune disease, or a neorodegenerative disease with these compounds.

Facile synthesis of 1,2-dione-containing abietane analogues for the generation of human carboxylesterase inhibitors

Recently, a series of selective human carboxylesterase inhibitors have been identified based upon the tanshinones, with biologically active molecules containing a 1,2-dione group as part of a naphthoquinone core. Unfortunately, the synthesis of such compounds is complex. Here we describe a novel method for the generation of 1,2-dione containing diterpenoids using a unified approach, by which boronic acids are joined to vinyl bromo-cyclohexene derivatives via Suzuki coupling, followed by electrocyclization and oxidation to the o-phenanthroquinones. This has allowed the construction of a panel of miltirone analogues containing an array of substituents (methyl, isopropyl, fluorine, methoxy) which have been used to develop preliminary SAR with the two human carboxylesterase isoforms. As a consequence, we have synthesized highly potent inhibitors of these enzymes (Ki 15 nM), that maintain the core tanshinone scaffold. Hence, we have developed a facile and reproducible method for the synthesis of abietane analogues that have resulted in a panel of miltirone derivatives that will be useful tool compounds to assess carboxylesterase biology.

BCL-2 INHIBITORS

The disclosure includes compounds of Formula (I) Formula (I) wherein W, R1, R2, R3, R4, R5, R6, rn, n, L, and Z1, are defined herein. Also disclosed is a method for treating a neoplastic disease and autoimmune disease with these compounds.

Gold-catalyzed cyclization of allenyl acetal derivatives

The gold-catalyzed transformation of allenyl acetals into 5-alkylidenecyclopent-2-en-1-ones is described. The outcome of our deuterium labeling experiments supports a 1,4-hydride shift of the resulting allyl cationic intermediates because a complete deuterium transfer is observed. We tested the reaction on various acetal substrates bearing a propargyl acetate, giving 4-methoxy-5-alkylidenecyclopent-2-en-1-ones 4 via a degradation of the acetate group at the allyl cation intermediate.