65510-83-0

Upstream product

• 40891-33-6 3,5-dimethoxyaniline hydrochloride 
• 141-97-9 ethyl acetoacetate 
• 10272-07-8 3.5-dimethoxyaniline 

Downstream Products

• 65510-99-8 d,l-5,7-dihydroxy-2-methyl-4-oxo-1,2,3,4-tetrahydroquinoline 

Relevant academic research and scientific papers

Novel diphenylmethyl compounds having mycobacterium tuberculosis inhibitory activity

The invention relates to novel diphenylmethyl derivatives having mycobacterium tuberculosis inhibitory activity and a preparation method thereof and particularly relates novel diphenylmethyl derivatives having activity for inhibiting replicative and non-replicating mycobacterium tuberculosis and a preparation method thereof. In particular, the invention relates to compounds shown in the formula (I) or all possible isomers, prodrugs, pharmaceutically acceptable salts, solvates or hydrates thereof, wherein the variables are as described in the specification. The invention also relates to the preparation method of the compounds and their pharmaceutical compositions and a use of the compounds in preparation of drugs for treating mycobacterium tuberculosis infection-caused diseases.

Derivatives of Natural Product Agrimophol as Disruptors of Intrabacterial pH Homeostasis in Mycobacterium tuberculosis

This article reports the rational medicinal chemistry of a natural product, agrimophol (1), as a new disruptor of intrabacterial pH (pHIB) homeostasis in Mycobacterium tuberculosis (Mtb). Through the systematic investigation of the structure-activity relationship of 1, scaffold-hopping of the diphenylmethane scaffold, pharmacophore displacement strategies, and studies of the structure-metabolism relationship, a new derivative 5a was achieved. Compound 5a showed 100-fold increased potency in the ability to reduce pHIB to pH 6.0 and similarly improved mycobactericidal activity compared with 1 against both Mycobacterium bovis-BCG and Mtb. Compound 5a possessed improved metabolic stability in human liver microsomes and hepatocytes, lower cytotoxicity, higher selectivity index, and similar pKa value to natural 1. This study introduces a novel scaffold to an old drug, resulting in improved mycobactericidal activity through decreasing pHIB, and may contribute to the critical search for new agents to overcome drug resistance and persistence in the treatment of tuberculosis.

Oximino-1-hydroxyoctahydrobenzo[c]quinolines and derivatives thereof

9-Amino-1-hydroxyoctahydrobenzo[c]quinoline derivatives of formula STR1 and pharmaceutically acceptable acid addition salts thereof wherein R is hydrogen, COR7 or SO2 R8 where R7 is hydrogen, alkyl, having from one to five carbon atoms; alkenyl and alkynyl each having from two to six carbon atoms; trifluoromethyl, benzyl, furyl, thienyl, pyridyl or R9 C6 H4 where R9 is H, NH2, F, Cl, Br, CH3 or OCH3 ; R8 is alkyl having from one to five carbon atoms or R9 C6 H4 ; R1 is hydrogen, benzyl, benzoyl, alkanoyl having from one to five carbon atoms or --CO--(CH2)p --NR2 R3 wherein p is 0 or an integer from 1 to 4; each of R2 and R3 when taken individually is hydrogen or alkyl having from one to four carbon atoms; R2 and R3 when taken together with the nitrogen to which they are attached form a 5- or 6-membered heterocyclic ring selected from piperidino, pyrrolo, pyrrolidino, morpholino or N-alkylpiperazino having from one to four carbon atoms in the alkyl group; R4 is hydrogen, alkyl having from 1 to 6 carbon atoms or --(CH2)z --C6 H5 wherein z is an integer from 1 to 4; R5 is hydrogen, methyl or ethyl; R6 is hydrogen, --(CH2)y -carbalkoxy having from one to four carbon atoms in the alkoxy group and wherein y is 0 or an integer from 1 to 4, carbobenzyloxy, formyl, alkanoyl having from two to five carbon atoms, alkyl having from one to six carbon atoms; --(CH2)x --C6 H5 wherein x is an integer from 1 to 4; or --CO(CH2)x-1 --C6 H5 ; Z is (a) alkylene having from one to nine carbon atoms; (b) -(alk1)m -X-(alk2)n - wherein each of (alk1) and (alk2) is alkylene having from one to nine carbon atoms, with the proviso that the summation of carbon atoms in (alk1) plus (alk2) is not greater than nine; each of m and n is 0 or 1; X is O, S, SO and SO2 ; and W is hydrogen, methyl, pyridyl, piperidyl, STR2 wherein W1 is selected from the group consisting of hydrogen, fluoro and chloro; and STR3 wherein W2 is hydrogen or STR4 is an integer from 1 to 5 and b is 0 or an integer from 1 to 5; with the proviso that the sum of a and b is not greater than 5; useful in mammals as analgesics, tranquilizers, antiemetic agents, diuretics, anticonvulsants, antidiarrheals, antitussives, in treatment of glaucoma, and intermediates therefore.