Day: October 26, 2021

Safety of 3-(Trifluoromethyl)phenol. In 2019 BIOORG CHEM published article about HUMAN DIHYDROOROTATE DEHYDROGENASE; DRUG in [Lu, Kuan; Zhao, Yanfang; Wu, Guodong; Hu, Hao; Jiang, Yuyang] Shenyang Pharmaceut Univ, Dept Pharmaceut Engn, Shenyang 110016, Liaoning, Peoples R China; [Lu, Kuan; Wang, Mingzhong] Sherushen Kivita Innovat Drug Discovery Inst, Sherushen 518057, Peoples R China; [Jiang, Yuyang] Tsinghua Univ, Natl & Local United Engn Lab Personalised Antitum, Grad Sch Shenshen, Shenzhen 518055, Peoples R China; [Jiang, Yuyang] Tsinghua Univ, Dept Pharmacol & Pharmaceut Sci, Sch Med, Beijing 100084, Peoples R China; [Gong, Guowei] Zunyi Med Univ, Dept Bioengn, Zhuhai Campus, Zhuhai 519041, Guangdong, Peoples R China in 2019, Cited 17. The Name is 3-(Trifluoromethyl)phenol. Through research, I have a further understanding and discovery of 98-17-9.

Human dihydroorotate dehydrogenase (hDHODH) is a flavin-dependent enzyme essential to pyrimidine de novo biosynthesis, which serves as an attractive therapeutic target for the treatment of autoimmune disorders. A novel series of hDHODH inhibitors was developed based on a lead which was obtained by a medicinal chemistry exploration. Most compounds showed moderate to significant potency against hDHODH, compounds 5d, 5e, and 6a effectively inhibited the activities of hDHODH with IC50 values from 0.9 to 2.8 mu M. Further studies showed that compound 5e also effectively suppressed proliferation of the activated PBMCs (IC50 = 20.35 mu M). Surprisingly, compound 5e also showed anti-pulmonary fibrotic activity similar to that of pirfenidone in vitro assay. Therefore, compound 5e might have potential to be developed as a novel hDHODH inhibitors for auto-immune diseases therapy.

About 3-(Trifluoromethyl)phenol, If you have any questions, you can contact Lu, K; Zhao, YF; Wu, GD; Hu, H; Wang, MZ; Gong, GW; Jiang, YY or concate me.. Safety of 3-(Trifluoromethyl)phenol

Reference:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
,Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Product Details of 123-11-5. Authors Obe, FO; Davis, RA; Spurlock, J; Barnes, MMG; Lindvall, T; Wendorf, MS; Delach, C; Ferrence, GM; Standard, JM; Hitchcock, SR in PERGAMON-ELSEVIER SCIENCE LTD published article about in [Obe, Fatima Olayemi; Davis, Ryan A.; Spurlock, Jennifer; Barnes, Morgan M. Grunloh; Lindvall, Tyler; Wendorf, Micah S.; Delach, Christina; Ferrence, Gregory M.; Standard, Jean M.; Hitchcock, Shawn R.] Illinois State Univ, Dept Chem, Normal, IL 61790 USA in 2021.0, Cited 32.0. The Name is 4-Methoxybenzaldehyde. Through research, I have a further understanding and discovery of 123-11-5

A series of Ephedra based oxadiazinones have been prepared, acylated, and examined in the asymmetric conjugate addition reaction with Grignard reagents in the presence of copper(I) bromide-dimethyl sulfide complex. The highest diastereoselectivity that was obtained in the conjugate addition reaction was observed with the (1R,2S)-ephedrine based N-4-methyloxadiazinone (5:1 d.r.) favoring the formation of the (S)-configuration of the conjugate addition product. Efforts to enhance the level of diaster-eoselection via increasing the steric volume of the stereo-directing N-4-substituent of the oxadiazinone (N-4- = p-methoxyphenyl or -isopropyl) led to an observed decrease in the level of diastereoselection. A computational study was conducted to examine the conformations adopted by the N-4-methyloxadiazinone vs. the N-4-isopropyl-oxadiazinone that yielded the lower diastereoselectivity. An argument is made for the stereoelectronic properties of the N-4-substituent being the cause of both the moderate diastereoselectivity and the unexpected facial preference for the conjugate addition. (C) 2021 Elsevier Ltd. All rights reserved.

Product Details of 123-11-5. About 4-Methoxybenzaldehyde, If you have any questions, you can contact Obe, FO; Davis, RA; Spurlock, J; Barnes, MMG; Lindvall, T; Wendorf, MS; Delach, C; Ferrence, GM; Standard, JM; Hitchcock, SR or concate me.

Reference:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
,Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

In 2019.0 J BIOTECHNOL published article about CONTINUOUS CHROMATOGRAPHY; AFFINITY SORBENTS; LIGAND in [Zhou, Tianyi; Wang, Lu; Zhang, Zhaoqing; Jin, Mi] Teva Pharmaceut USA Inc, CMC Biol, W Chester, PA USA in 2019.0, Cited 26.0. The Name is Benzyl Alcohol. Through research, I have a further understanding and discovery of 100-51-6. Recommanded Product: Benzyl Alcohol

Effective Protein A column regeneration is important in therapeutic monoclonal antibody (mAb) production for product quality and process economics. To design a robust and effective regeneration strategy, resin compatibility, microbial inactivation efficiency and cleaning effectiveness are three major considerations. Regenerating Protein A column using acidic (e.g. acetic acid) and/or caustic (e.g. NaOH) solutions is a common approach. However, it is challenging to balance between resin performance decline and adequate microbial control in choosing the right caustic solution concentration, even for resin with enhanced caustic tolerance such as MabSelect SuRe. This report introduces an enhanced regeneration strategy for MabSelect SuRe resin. The approach applies benzyl alcohol in low concentration acetic acid and NaOH (100 mM) solutions in sequential steps to regenerate MabSelect SuRe resin for reuse. Such solutions demonstrated good resin compatibility in resin functional test after extended solution incubation time, and demonstrated superior microbial control using eight test microorganisms. The cleaning effectiveness of the proposed strategy is demonstrated by carryover study, where product and impurity carryover was below detection limit. Finally, during a resin lifetime study, consistent step yields and product quality attributes were demonstrated, and no carryover was observed, up to 150 purification cycles. A viral clearance study further demonstrated that aged resin at the end of the resin lifetime had comparable viral clearance performance compared to new resin. No active virus was detected in the elution pool of the subsequent blank runs. These studies further verified the robustness of the proposed regeneration strategy for MabSelect SuRe resin.

Recommanded Product: Benzyl Alcohol. About Benzyl Alcohol, If you have any questions, you can contact Zhou, TY; Wang, L; Zhang, ZQ; Jin, M or concate me.

Reference:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
,Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

In 2021.0 EUR J ORG CHEM published article about ALCOHOLS; FLUORINE; OXALATES in [Zemtsov, Artem A.; Lunkov, Sergey S.; Levin, Vitalij V.; Dilman, Alexander D.] ND Zelinskii Inst Organ Chem, Leninsky Prosp 47, Moscow 119991, Russia; [Lunkov, Sergey S.] Moscow MV Lomonosov State Univ, Dept Chem, Leninskie Gory 1-3, Moscow 119991, Russia in 2021.0, Cited 39.0. The Name is 3,4-Dimethoxybenzaldehyde. Through research, I have a further understanding and discovery of 120-14-9. SDS of cas: 120-14-9

A method for the synthesis of trifluoromethyl-substituted dithiocarbamates from aldehydes is described. The reaction involves nucleophilic trifluoromethylation, derivatization of the silyloxy-group with pentafluoropyridine, and substitution of the fluorinated pyridinyloxy group by dithiocarbamate anion. The substitution step is performed in the presence of 12-phenyl-12H-benzo[b]phenothiazine and copper cyanide under irradiation of 400 nm LED.

SDS of cas: 120-14-9. About 3,4-Dimethoxybenzaldehyde, If you have any questions, you can contact Zemtsov, AA; Lunkov, SS; Levin, VV; Dilman, AD or concate me.

Reference:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
,Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Formula: C7H8O. In 2021.0 GREEN CHEM published article about DEHYDROGENATION; EFFICIENT in [Wang, Jingjing; Jiang, Feng] Gannan Med Univ, Key Lab Cardiovasc & Cerebrovasc Dis Prevent & Co, Minist Educ, Ganzhou 341000, Jiangxi, Peoples R China; [Wang, Jingjing; Ruhlmann, Laurent] Univ Strasbourg, Inst Chim, Lab Electrochim & Chim Phys Corps Solide, UMR CNRS 7177, 4 Rue Blaise Pascal,CS 90032, F-67081 Strasbourg, France; [Tao, Chaofu; Yu, Han] Shanghai Inst Technol, Sch Chem & Environm Engn, Shanghai 201418, Peoples R China; [Yu, Han; Wei, Yongge] Tsinghua Univ, Dept Chem, Key Lab Organ Optoelect & Mol Engn, Minist Educ, Beijing 100084, Peoples R China; [Yu, Han; Wei, Yongge] Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China in 2021.0, Cited 19.0. The Name is Benzyl Alcohol. Through research, I have a further understanding and discovery of 100-51-6.

The direct esterification of alcohols with non-noble metal-based catalytic systems faces great challenges. Here, we report a new chrome-based catalyst stabilized by a single pentaerythritol decorated Anderson-type polyoxometalate, [N(C4H9)(4)](3)[CrMo6O18(OH)(3)C{(OCH2)(3)CH2OH}], which can realize the efficient transformation from alcohols to esters by H2O2 oxidation in good yields and high selectivity without extra organic ligands. A variety of alcohols with different functionalities including some natural products and pharmaceutical intermediates are tolerated in this system. The chrome-based catalyst can be recycled several times and still keep the original configuration and catalytic activity. We also propose a reasonable catalytic mechanism and prove the potential for industrial applications.

Formula: C7H8O. About Benzyl Alcohol, If you have any questions, you can contact Wang, JJ; Jiang, F; Tao, CF; Yu, H; Ruhlmann, L; Wei, YG or concate me.

Reference:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
,Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

I found the field of Chemistry very interesting. Saw the article Structure-Based Design of Dimeric Bisbenzimidazole Inhibitors to an Emergent Trimethoprim-Resistant Type II Dihydrofolate Reductase Guides the Design of Monomeric Analogues published in 2019.0. Safety of 3-Hydroxybenzaldehyde, Reprint Addresses Pelletier, JN (corresponding author), Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada.; Pelletier, JN (corresponding author), Univ Montreal, Dept Chim, Montreal, PQ H3C 3J7, Canada.; Pelletier, JN (corresponding author), PROTEO, Quebec Network Res Prot Funct Engn & Applicat, Quebec City, PQ G1V 0A6, Canada.; Pelletier, JN (corresponding author), CGCC, Montreal, PQ H3A 0B8, Canada.. The CAS is 100-83-4. Through research, I have a further understanding and discovery of 3-Hydroxybenzaldehyde

The worldwide use of the broad-spectrum antimicrobial trimethoprim (TMP) has induced the rise of TMP-resistant microorganisms. In addition to resistance-causing mutations of the microbial chromosomal dihydrofolate reductase (Dfr), the evolutionarily and structurally unrelated type II Dfrs (DfrBs) have been identified in TMP-resistant microorganisms. DfrBs are intrinsically TMP-resistant and allow bacterial proliferation when the microbial chromosomal Dfr is TMP-inhibited, making these enzymes important targets for inhibitor development. Furthermore, DfrBs occur in multiresistance plasmids, potentially accelerating their dissemination. We previously reported symmetrical bisbenzimidazoles that are the first selective inhibitors of the only well-characterized DfrB, DfrB1. Here, their diversification provides a new series of inhibitors (K-i = 1.7-12.0 mu M). Our results reveal two prominent features: terminal carboxylates and inhibitor length allow the establishment of essential interactions with DfrB1. Two crystal structures demonstrate the simultaneous binding of two inhibitor molecules in the symmetrical active site. Observations of those dimeric inhibitors inspired the design of monomeric analogues, binding in a single copy yet offering similar inhibition potency (K-i = 1.1 and 7.4 mu M). Inhibition of a second member of the DfrB family, DfrB4, suggests the generality of these inhibitors. These results provide key insights into inhibition of the highly TMP-resistant DfrBs, opening avenues to downstream development of antibiotics for combatting this emergent source of resistance.

About 3-Hydroxybenzaldehyde, If you have any questions, you can contact Toulouse, JL; Yachnin, BJ; Ruediger, EH; Deon, D; Gagnon, M; Saint-Jacques, K; Ebert, MCCJC; Forge, D; Bastien, D; Colin, DY; Eynde, JJV; Marinier, A; Berghuis, AM; Pelletier, JN or concate me.. Safety of 3-Hydroxybenzaldehyde

Reference:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
,Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Jarrahi, M; Tayebee, R; Maleki, B; Salimi, A in [Jarrahi, Mahbube; Tayebee, Reza; Maleki, Behrooz] Hakim Sabzevari Univ, Sch Sci, Dept Chem, Sabzevar 9617976487, Iran; [Salimi, Alireza] Ferdowsi Univ Mashhad, Fac Sci, Dept Chem, Mashhad, Razavi Khorasan, Iran published One-pot multicomponent green LED photoinduced synthesis of chromeno[4,3-b]chromenes catalyzed by a new nanophotocatalyst histaminium tetrachlorozincate in 2021, Cited 57. Recommanded Product: 123-11-5. The Name is 4-Methoxybenzaldehyde. Through research, I have a further understanding and discovery of 123-11-5.

Histaminium tetrachlorozincate nanoparticles are prepared, characterized and applied as an effective and recoverable photocatalyst in the one-pot, green and multi-component synthesis of various chromenes by the reaction of dimedone and/or 1,3-cyclohexanedione, arylaldehyde and 4-hydroxycoumarin in high yields under solventless conditions at ambient temperature. This new catalyst is characterized by FT-IR, XRD, EDX, NMR, SEM and TEM techniques. The incorporation of histaminium ions into the framework of ZnCl42- significantly affected the photocatalytic activity of tetrachlorozincate such that good reusability and recyclability are attained. Moreover, reactive species such as O-2(-) and hydroxyl radicals have proved to be active species in the presented photocatalytic reaction. In addition, the hot filtration test confirms enough stability of the photocatalyst and no significant leaching and destruction of the framework in the course of the reaction. The major advantages of the presented methodology include easy work-up, cost effectiveness, nontoxic nature, broad substrate scope, 100% atom economy, ease of separation, and environment friendly reaction conditions. Finally, the catalyst could be reused many times without significant loss of activity.

Recommanded Product: 123-11-5. About 4-Methoxybenzaldehyde, If you have any questions, you can contact Jarrahi, M; Tayebee, R; Maleki, B; Salimi, A or concate me.

Reference:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
,Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

An article C-2-Symmetric Cinchona Alkaloid Derivatives: Versatile Catalysts for the Enantioselective C-C Bond Forming Conjugate Addition of Nucleophiles to Simple alpha,beta-Unsaturated Acyl Pyrazoles WOS:000603432100011 published article about CHIRAL LEWIS-ACID; MICHAEL ADDITION; ASYMMETRIC REACTION; DIELS-ALDER; CYCLOADDITIONS; NITROMETHANE; PROPIOLOYLPYRAZOLES; BENZYLHYDROXYLAMINE; MALONONITRILE; ACTIVATION in [Curran, Simon P.; Fallon, Brendan J.; Connon, Stephen J.] Trinity Coll Dublin, Trinity Biomed Sci Inst, Sch Chem, 152-160 Pearse St, Dublin 2, Ireland in 2020, Cited 57. HPLC of Formula: C5H8O2. The Name is (E)-2-Methylbut-2-enoic acid. Through research, I have a further understanding and discovery of 80-59-1

A single C-2-symmetric squaramide catalyst system allows the facile addition of either malononitrile or benzyl nitroacetate to simple pyrazole-based Michael acceptors with excellent enantiocontrol and at lower catalyst loadings than previously possible. The latter reactions are not diastereoselective, however facile hydrogenolysis leads to decarboxylation and formation of the formal adduct from the addition of nitromethane (a very recalcitrant nucleophile in this chemistry) with excellent yield and enantiocontrol.

About (E)-2-Methylbut-2-enoic acid, If you have any questions, you can contact Curran, SP; Fallon, BJ; Connon, SJ or concate me.. HPLC of Formula: C5H8O2

Reference:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
,Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Authors Kayamba, F; Malimabe, T; Ademola, IK; Pooe, OJ; Kushwaha, ND; Mahlalela, M; van Zyl, RL; Gordon, M; Mudau, PT; Zininga, T; Shonhai, A; Nyamori, VO; Karpoormath, R in ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER published article about MOLECULAR-DYNAMICS; ASSAY in [Kayamba, Francis; Kushwaha, Narva Deshwar; Mahlalela, Mavela; Karpoormath, Rajshekhar] Univ KwaZulu Natal, Coll Hlth Sci, Dept Pharmaceut Chem, ZA-4000 Durban, South Africa; [Malimabe, Teboho; van Zyl, Robyn L.] Univ Witwatersrand, Fac Hlth Sci, Dept Pharm & Pharmacol, Pharmacol Div, ZA-2193 Johannesburg, South Africa; [Malimabe, Teboho; van Zyl, Robyn L.] Univ Witwatersrand, Fac Hlth Sci, WITS Res Inst Malaria WRIM, ZA-2193 Johannesburg, South Africa; [Ademola, Idowu Kehinde; Gordon, Michelle] Univ KwaZulu Natal, Coll Hlth Sci, Sch Lab Med & Med Sci, ZA-4000 Durban, South Africa; [Pooe, Ofentse Jacob] Univ KwaZulu Natal, Sch Life Sci, Discipline Biochem, ZA-4000 Durban, South Africa; [Mudau, Pertunia T.; Zininga, Tawanda] Univ Venda, Sch Math & Nat Sci, Dept Biochem, ZA-0950 Thohoyandou, South Africa; [Zininga, Tawanda; Shonhai, Addmore] Stellenbosch Univ, Dept Biochem, ZA-7600 Stellenbosch, South Africa; [Nyamori, Vincent O.] Univ KwaZulu Natal, Sch Chem & Phys, Westville Campus, ZA-4000 Durban, South Africa in 2021, Cited 43. Quality Control of 3,4-Dimethoxybenzaldehyde. The Name is 3,4-Dimethoxybenzaldehyde. Through research, I have a further understanding and discovery of 120-14-9

Presently, artemisinin-based combination therapy (ACT) is the first-line therapy of Plasmodium falciparum malaria. With the emergence of malaria parasites that are resistant to ACT, alternative antimalarial therapies are urgently needed. In line with this, we designed and synthesised a series of novel N-(7chloroquinolin-4-yl)-N’-(4,6-diphenylpyrimidin-2-yl)alkanediamine hybrids (6a-7c) and evaluated their inhibitory activity against the NF54 chloroquine-susceptible strain as a promising class of antimalarial compounds. The antiplasmodial screening revealed that seven analogues showed promising to good activity with half-maximal inhibitory concentration ( IC50) = 0.32 mu Me4.30 mM. Compound 7a with 1,4-diamine butyl linker and 4-hydroxyl phenyl on fourth and sixth position of pyrimidine core showed the most prominent activity with an IC50 value of 0.32 +/- 0.06 mM, with a favourable safety profile of 9.79 to human kidney epithelial (HEK293) cells. The remaining six analogues showed moderate activity with IC50 values ranging from 7.50 mM to 83.01 mM. We further investigated the binding affinities of the molecules to two essential cytosolic P. falciparum heat shock protein 70 homologues; PfHsp70-1 and PfHsp70-z. Compound 7a exhibited the highest binding affinity for both PfHsp70s with K-D in a lower nanomolar range (4.4-11.4 nM). Furthermore, molecular docking revealed that compounds 6, 6k, 7b and 7a exhibited better fitness in PfHsp70-1 with compound 7a showing the highest and lowest binding scores of similar to 9.8 kcal/mol. Therefore, we speculate that PfHsp70-1 is one of the targets of these inhibitors. The bioisoteric replacement of the groups at phenyl ring at the fourth and sixth position of the pyrimidine core had a constructive association with antiplasmodial activity. The promising antiplasmodial activity of the synthesised analogues illustrates how crucial molecular hybridisation is as a strategy in the development of quinoline-pyrimidine hybrids as prospective antiprotozoal agents. (C) 2021 Elsevier Masson SAS. All rights reserved.

Quality Control of 3,4-Dimethoxybenzaldehyde. About 3,4-Dimethoxybenzaldehyde, If you have any questions, you can contact Kayamba, F; Malimabe, T; Ademola, IK; Pooe, OJ; Kushwaha, ND; Mahlalela, M; van Zyl, RL; Gordon, M; Mudau, PT; Zininga, T; Shonhai, A; Nyamori, VO; Karpoormath, R or concate me.

Reference:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
,Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Recently I am researching about MULTICOMPONENT SYNTHESIS; DERIVATIVES; EFFICIENT; CATALYST; MILD, Saw an article supported by the . Published in ELSEVIER in AMSTERDAM ,Authors: Tabassum, S; Devi, KRS; Govindaraju, S. The CAS is 120-14-9. Through research, I have a further understanding and discovery of 3,4-Dimethoxybenzaldehyde. Safety of 3,4-Dimethoxybenzaldehyde

The investigation presents a straightforward synthesis of fifteen 1,4-dihydropyrano[2,3-c]pyrazoles using ZnO@PEG nanocatalyst in ethanol via Multicomponent approach under the influence of ultrasound. The present methodology successively tolerates a variety of functional groups and offers several advantages such as excellent yields without chromatographic purification, milder reaction conditions, shorter reaction times, and the use of an environmentally benign reusable catalyst. Ecstatically, the reaction was successfully scaled to gram level ascertaining the wider applicability of ZnO@PEG nanoparticles in multicomponent reactions. (C) 2019 Elsevier Ltd. All rights reserved.

About 3,4-Dimethoxybenzaldehyde, If you have any questions, you can contact Tabassum, S; Devi, KRS; Govindaraju, S or concate me.. Safety of 3,4-Dimethoxybenzaldehyde

Reference:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
,Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles