Indole-3-acetic acid, structure

NSAIDs are of diverse chemical structures salicylates (aspirin, sulphasalazine), indole acetic acids (indomethacin, etodolac), heteroaryl acetic acids (diclofenac), arylpropionic acids (ibuprofen, naproxen), anthranilic acids (mefenamic acid) and enolic acids (piroxicam, meloxicam). 

Indomethacin and Analogs - Among several isosteric modifications of indomethacin studied at Merck, an indene isoster, cis -1-p-chloro-benzylidenyl-5-methoxy-2-methyl-3-indenylacetic acid (VII), was found to be half as active as indomethacin. The corresponding "trans isomer was only one-tenth as active. The structure-activity relationship of Nj-aroyl and N.-aralkyl indole acetic acids is generally parallel to that of indene isosters, indicative of a similar mode of action. Based on X-ray diffraction data, the nonplanar configuraticn of the cis-isomer was suggested as the preferred conformation of... 

Fig. 1. Structures of indole acetic acid hapten-protein conjugates.

Similarly, nicotinamide was shown to form co-crystals with dodecanoic acid and indole acetic acid, and iso-nicotinamide with phloroglocinol and hydroquinone (Figure 7.7) [14b, c, e]. All these structures contain synthon I. The -COOH or -OH groups interact with the pyridine moiety and also with the second N-H group of amide which is not a part of synthon I. All these structures indicate that the acid-pyridine synthon is favoured over amide-acid according to the hierarchy of the interactions. 

Figure 5.39 Structure of indole acetic acid and glucobrassicin.

FIGURE 13.7 Structures for indene and indole acetic acid. 

Several derivatives of indolo[3,2-fi]carbazole, such as the system 185, have been claimed to arise from the reaction of suitably substituted simple indoles on treatment with thallium triacetate in acetic acid. A compound having the purported structure of 185 was thus isolated when 2,3-dimethylindole was used as the substrate [78UC(B)422]. Many years later, it was demonstrated that this product is in fact a derivative of indolo[2,3-c]carbazole (cf. Section VI) (99T12595). 

APX, ascorbate peroxidase PJiP, Arthromyces ramosus peroxidase BPl, barley grain peroxidase CCP, C3dochrome c peroxidase CIP, Coprinus cinereus peroxidase EXAFS, extended X-ray absorption fine structure HRP, horseradish peroxidase HRP Z (where Z = A1-A3, B1-B3, Cl, C2, D, E1-E6, or N), a specific isoenzyme of horseradish peroxidase HS, high-spin lAA, indole-3-acetic acid LIP, hgnin peroxidase LS, low-spin PNP, the major cationic isoenzyme of peanut peroxidase WT, wild-type 5-c, five-coordinate 6-c, six-coordinate. 

Structural information on aromatic donor molecule binding was obtained initially by using H NMR relaxation measurements to give distances from the heme iron atom to protons of the bound molecule. For example, indole-3-propionic acid, a structural homologue of the plant hormone indole-3-acetic acid, was found to bind approximately 9-10 A from the heme iron atom and at a particular angle to the heme plane (234). The disadvantage of this method is that the orientation with respect to the polypeptide chain cannot be defined. Other donor molecules examined include 4-methylphenol (p-cresol) (235), 3-hydroxyphenol (resorcinol), 2-methoxy-4-methylphenol and benzhydroxamic acid (236), methyl 2-pyridyl sulfide and methylp-tolyl sulfide (237), and L-tyrosine and D-tyrosine (238). Distance constraints of between 8.4 and 12.0 A have been reported (235-238). Aromatic donor proton to heme iron distances of 6 A reported earlier for aminotriazole and 3-hydroxyphenol (resorcinol) are too short because of an inappropriate estimate of the molecular correlation time (239), a parameter required for the calculations. Distance information for a series of aromatic phenols and amines bound to Mn(III)-substituted HRP C has been published (240). 

The largest number of indole derivatives which have been structurally characterized are the indole alkaloids these mainly arise from plant sources. Not unexpectedly, in view of tryptophan s status as one of the essential amino acids, there are also diverse derivatives found in microorganisms. Indole-3-acetic acid plays a major role in plant metabolism, being a growth regulator (74MI30600). 

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