Novel antituberculosis and antileprotic agents. 1-[3-[[5,6,7,8-tetrahydro-4-(phenylazo- and 3-pyridylazo)-1-naphthyl]amino]propyl]piperidines and related compounds

Abstract

A variety of N-monoand N,N-dialkyI-N'-[4-azo(5,6,7,8-tetrahydro-l-naphthyl-and -2,3-xylyl)] alkylenediamines were synthesized by (1) coupling a diazotized aromatic or heterocyclic amine with the requisite N,N-dialkyl-N'-(5,6,7,8-tetrahydro-l-naphthylor -2,3-xylyl)alkylenediamine, (2) condensation of N-(3-bromopropyl)-516,7,8-tetrahydro-4-phenyIazo-l-naphthylamine with the appropriate amine, and (3) alkaline hydrolysis of the corresponding N-(ammoalkyl)-2,2,2-trifluoro-N-(5,6,7,8-tetrahydro-4-azo-l-naphthyl)acetamides. Potent in vitro antituberculosis activity among the N-monoand N,N-dialkyl-N'-[4-azo(5,6,7,8-tetrahydro-l-naphthyland -2,3-xylyl)] alkylenediamines is widespread, and 28 compounds exhibited a similar order of potency as isoniazid. However, activity against Mycobacterium tuberculosis H37Rv in mice is relatively specific, and strong effects were observed only among the l-(3-{ [5,6,7,8-tetrahydro-4-(phenylazo)-1-naphthyl] amino)propyl)piperidines (I) and l-(3-j [5,6,7,8-tetrahydro-4-(3-pyridylazo)-l-naphthyl] amino }propyl)piperidines (II). Four representative compounds among the latter types also showed definite suppressive antileprotic activity against M. lepraemurium in mice. Structure-activity relationships are discussed. also thank Dr.

Pyrazolone Derivatives: Synthesis, Anti-inflammatory, Analgesic, Quantitative Structure–Activity Relationship and <i>in Vitro</i> Studies

“…Therefore, synthetic approaches based upon chemical modification of NSAIDs were taken with the aim of improving NSAID safety profile. [7][8][9][10] The core pyrazolone structure generally attracted widespread attention because of the diversity of biological activity as they showed anti-inflammatory [11][12][13] analgesic, 14,15) antitumor, 16) antimicrobial, 17,18) hypoglycemic, 19) and antitubercular 20) activities. One of the first synthetic organic compounds that used as an important drug and having a pyrazolone nucleus was antipyrine I.…”

Synthetic schistosomicides. XVII. N-(Benzylidene and cinnamylidene)-N'-[2-(diethylamino)ethyl]-1,4-naphthalenediamines and related Schiff bases

“…and XV) completely eliminated live schistosomes from infected mice at doses ranging from (iti to 271 mg kg per day when administered orally in the diet for 14 days.23 These compounds, therefore, possessed distinctly more promising antischistosome activity in mice than lucanthone hydrochloride.22•24 hycanthone,'-'•'' the tris(p-aminophenyl)carbonium A'-15-l/namit lojihenox \•) pentyl jphthalimidc.2"' or 3-[4-(3-chloro-/ntolyl)-l-piperazÍTiylcarbonyl ¡acrylic acid411 when tested under comparable experimental conditions.22•22 Moreover. l(i other Schiff bases 11 3, 5, 9 12, 15, 16, 19, 20, Xa and b. XI and XIV) effected a marked reduction (32 97%.) in live worms at daily diet doses of 79 2N7 mg kg for 14 days.23 The .V-(benzylidene and chmamylidvnej-l-iiaph thy lamine derivatives XVI•-XVIII lacked appreciable antischistosome effects at doses of 271 31b mg, kg.…”

“…A -Benzy lidene -A'-[2-(diethy lamino )ethyl] -1,4-naphthalenediamines (VIII) (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)Table I). -A solution of 8.4 g (0.024 mol) of .V-[2-(diethylamino)ethyl]-1,4-naphthalenediamine • 2HC115 in ice water was made strongly basic with NH4OH and the mixture was extracted with 600 ml of xylene.…”

3-(2,6-Dioxopiperidin-3-yl)-3-azabicyclo[3.2.0]heptane-2,4-dione

“…For related structures, see: Muller & Man (2008); Yamamoto et al (2008); Zeldis (2008). For related literature, see: Carson et al (2004); Werbel et al (1968); Cremer & Pople (1975); Schmidt & Polik (2007).…”

“…The synthesis and biological evaluation of the title compound, 3-(2,6-dioxopiperidine-3-yl)-3-azabicyclo-[3.2.0]heptane-2,4-dione and its analogues is of interest to synthetic medicinal chemists. Specifically, piperidine 2,6dione derivatives, including those of phthalimide, are important anti-angiogenic and immunomodulative agents used for the treatment of many diseases including multiple myeloma, (Muller & Man, 2008;Yamamoto et al, 2008;Zeldis, 2008), Chron's disease (Carson et al, 2004), and leprosy (Werbel et al, 1968). The title molecule, C 11 H 12 N 2 O 4 , a piperidine 2,6dione derivative, consists of an azabicyclo[3.2.0]heptane group containing a nearly planar cyclobutane ring, fused to a pyrrolidine ring, bonded to a 2,6-dioxopiperidine ring at the 3 position.…”