The major metabolite of ketoconazole appears to be M2, an end product resulting from oxidation of the imidazole moiety. CYP3A4 is known to be the primary contributor to this reaction with some contribution from CYP2D6. Other metabolites resulting from CYP3A4 mediated oxidation of the imidazole moiety include M3, M4, and M5. Ketoconazole may also undergo N-deacetylation to M14, , alkyl oxidation to M7, N-oxidation to M13, or aromatic hydroxylation to M8, or hydroxylation to M9. M9 may further undergo oxidation of the hydroxyl to form M12, N-dealkylation to form M10 with a subsequent N-dealkylation to M15, or may form an iminium ion. No metabolites are known to be active however oxidation metabolites of M14 have been implicated in cytotoxicity.
Ketoconazole is partially metabolized, in the liver, to several inactive metabolites by oxidation and degradation of the imidazole and piperazine rings, by oxidative O-dealkylation, and by aromatic hydroxylation.
Hepatic. Ketoconazole is partially metabolized in the liver to several inactive metabolites by oxidation and degradation of the imidazole and piperazine rings, by oxidative O-dealkylation, and by aromatic hydroxylation. (A625)
Half Life: 2 hours
IDENTIFICATION AND USE: Ketokonazole is used as antifungal medication. HUMAN EXPOSURE AND TOXICITY: Transient increases in serum AST, ALT, and alkaline phosphatase concentrations may occur during ketoconazole therapy. Serious hepatotoxicity has occurred in patients receiving oral ketoconazole, including cases that were fatal or required liver transplantation. Hepatotoxicity may be hepatocellular (in most cases), cholestatic, or a mixed pattern of injury. Although ketoconazole-induced hepatotoxicity usually is reversible following discontinuance of the drug, recovery may take several months and rarely death has occurred. Symptomatic hepatotoxicity usually is apparent within the first few months of ketoconazole therapy, but occasionally may be apparent within the first week of therapy. Some patients with ketoconazole-induced hepatotoxicity had no obvious risk factors for liver disease. Serious hepatotoxicity has been reported in patients receiving high oral ketoconazole dosage for short treatment durations and in patients receiving low oral dosage of the drug for long durations. Many of the reported cases of hepatotoxicity occurred in patients who received the drug for the treatment of tinea unguium (onychomycosi or the treatment of chronic, refractory dermatophytoses. Ketoconazole-induced hepatitis has been reported in some children. Usual dosages (ie, 200-400 mg daily) of ketoconazole have been reported to transiently (for 2-12 hours) inhibit testicular testosterone synthesis. A compensatory increase in serum luteinizing hormone (LH) concentrations may occur. Dosages of 800-1200 mg daily have been reported to have a more prolonged effect on testosterone synthesis; in one study in males receiving these high dosages, serum testosterone concentrations remained at a subnormal level (ie, less than 300 ng/dL) throughout the day in about 30% of those receiving 800 mg daily and in all of those receiving 1200 mg daily. Oligospermia, decreased libido, and impotence often occurred in these males and azoospermia occurred rarely. The drug apparently directly inhibits synthesis of adrenal steroids and testosterone in vitro and in vivo. Ketoconazole appears to inhibit steroid synthesis principally by blocking several P-450 enzyme systems (eg, 11beta-hydroxylase, C-17,20-lyase, cholesterol side-chain cleavage enzyme). Overall the results show that many of the commonly used azole fungicides act as endocrine disruptors in vivo, although the profile of action in vivo varies. As ketoconazole is known to implicate numerous endocrine-disrupting effects in humans. ANIMAL STUDIES: After oral administration toxicity was manifested in mice, rats and guinea pigs by sedation, catalepsy, ataxia, tremors, convulsions and pre-lethal loss of the righting reflex at doses >320 mg/kg. In dogs, toxicity was manifested by diarrhea and vomiting at doses >80 mg/kg. Ketoconazole has been administered by the oral (gavage) and intravenous routes to mice, rats, guinea pigs and dogs. Toxicity after intravenous administration was manifested by spasms, convulsions and dyspnea in rats, mice and guinea pigs; pre-lethal loss of the righting reflex occurred in mice and guinea pigs, and dogs. Toxicity in dogs was also manifested by licking and convulsions. In rats the overall incidence of and type of tumors was not significantly different between treated and control groups, except for high-dosed female rats who had a decrease of the overall tumor rate. In developmental studies in rats the incidence of stillborn fetuses increased from a control value of 0.5% to 32.7% in rats dosed with 40 mg/kg and cannibalization of young occurred in two litters. In mice a significant decline in sperm motility and density in cauda epididymis was noted. A sharp decline in fertility (50% negative) in ketoconazole treated mice was observed. A significant reduction in the total protein and sialic acid contents of testes, epididymis, seminal vesicle and ventral prostate were noticed. The cholesterol contents of testes were raised while fructose contents of seminal vesicle were reduced significantly. The ketoconazole treatment altered the biochemical milieu of the reproductive tract. In the rabbit, ketoconazole produces evidence of maternal toxicity, embryotoxicity and teratogenicity at a high dose of 40 mg/kg/day. Ketoconazole did not show any signs of mutagenic potential when evaluated using the dominant lethal mutation test or the Ames Salmonella microsomal activator assay. ECOTOXICITY STUDIES: Ketoconazole induced CYP1A and CYP3A expression in rainbow trout. However, the most pronounced effect of ketoconazole was a 60 to 90% decrease in CYP3A catalytic activities in rainbow trout and in killifish.
Ketoconazole interacts with 14-α demethylase, a cytochrome P-450 enzyme necessary for the conversion of lanosterol to ergosterol. This results in inhibition of ergosterol synthesis and increased fungal cellular permeability. Other mechanisms may involve the inhibition of endogenous respiration, interaction with membrane phospholipids, inhibition of yeast transformation to mycelial forms, inhibition of purine uptake, and impairment of triglyceride and/or phospholipid biosynthesis. Ketoconazole can also inhibit the synthesis of thromboxane and sterols such as aldosterone, cortisol, and testosterone. (A1990, A1991, A1992, A1993)
Mild and transient elevations in liver enzymes occur in 4% to 20% of patients on oral ketaconazole. These abnormalities are usually transient and asymptomatic and uncommonly require dose adjustment or discontinuation. Clinically apparent hepatotoxicity from ketaconazole is well described in the literature and is estimated to occur in 1:2,000 to 1:15,000 users. The liver injury typically presents with an acute hepatitis-like picture 1 to 6 months after starting therapy. While most cases present with a hepatocellular pattern of injury, cholestatic forms have been described. Rash, fever and eosinophilia are rare as is autoantibody formation. Recovery upon stopping therapy may be delayed and generally takes 1 to 3 months. Severe cases with acute liver failure and death or need for emergency liver transplantation have been described.
Ketoconazole requires an acidic environment to become soluble in water. At pH values above 3 it becomes increasingly insoluble with about 10% entering solution in 1 h. At pH less than 3 dissolution is 85% complete in 5 min and entirely complete within 30 min. A single 200 mg oral dose produces a Cmax of 2.5-3 mcg/mL with a Tmax of 1-4 h. Administering ketoconazole with food consistently increases Cmax and delays Tmax but literature is contradictory regarding the effect on AUC, which may experience a small decrease. A bioavailablity of 76% has been reported for ketoconazole.
来源:DrugBank
吸收、分配和排泄
消除途径
仅有2-4%的酮康唑剂量以不变的形式在尿液中排出。超过95%通过肝脏代谢消除。
Only 2-4% of the ketoconazole dose is eliminated unchanged in the urine. Over 95% is eliminated through hepatic metabolism.
Ketoconazole has an estimated volume of distribution of 25.41 L or 0.36 L/kg. It distributes widely among the tissues, reaching effective concentrations in the skin, tendons, tears, and saliva. Distribution to vaginal tissue produces concentrations 2.4 times lower than plasma. Penetration into the CNS, bone, and seminal fluid are minimal. Ketoconazole has been found to enter the breast milk and cross the placenta in animal studies.
来源:DrugBank
吸收、分配和排泄
清除
酮康唑的估计清除率为8.66升/小时。
Ketoconazole has an estimated clearance of 8.66 L/h.
来源:DrugBank
吸收、分配和排泄
酮康唑可迅速从胃肠道吸收。口服给药后，酮康唑在胃液中溶解并转化为盐酸形式，然后从胃部吸收。
Ketoconazole is rapidly absorbed from the GI tract. Following oral administration, ketoconazole is dissolved in gastric secretions and converted to the hydrochloride salt prior to absorption from the stomach.
[EN] BENZAMIDE OR BENZAMINE COMPOUNDS USEFUL AS ANTICANCER AGENTS FOR THE TREATMENT OF HUMAN CANCERS<br/>[FR] COMPOSÉS BENZAMIDE OU BENZAMINE À UTILISER EN TANT QU'ANTICANCÉREUX POUR LE TRAITEMENT DE CANCERS HUMAINS
申请人：UNIV TEXAS
公开号：WO2017007634A1
公开（公告）日：2017-01-12
The described invention provides small molecule anti-cancer compounds for treating tumors that respond to cholesterol biosynthesis inhibition. The compounds selectively inhibit the cholesterol biosynthetic pathway in tumor-derived cancer cells, but do not affect normally dividing cells.
[EN] ACC INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE L'ACC ET UTILISATIONS ASSOCIÉES
申请人：GILEAD APOLLO LLC
公开号：WO2017075056A1
公开（公告）日：2017-05-04
The present invention provides compounds I and II useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same.
Heterocyclic derivatives for the treatment of cancer and other proliferative diseases
申请人：——
公开号：US20020143182A1
公开（公告）日：2002-10-03
The invention relates to certain heterocyclic compounds useful for the treatment of cancer and other diseases, having the Formula (I):
1
wherein:
(a) m is an integer 0 or 1;
(b) R
12
is an alkyl, a substituted alkyl, a cycloalkyl, a substituted cycloalkyl, a heterocyclic, a substituted heterocyclic, a heteroaryl, a substituted heteroaryl, an aryl or a substituted aryl residue;
(c) Ar
3
is an aryl, a substituted aryl, a heteroaryl or a substituted heteroaryl residue;
(d) Ar
4
is an aryl, a substituted aryl, a heteroaryl or a substituted heteroaryl residue;
(e) R
5
is hydrogen, hydroxy, alkyl or substituted alkyl;
(f) - - - - - represents a bond present or absent; and
(g) W, X, Y and Z are independently or together C(O)—, C(S), S, O, or NH; or a pharmaceutically acceptable salt thereof.
Tricyclic compounds, protected intermediates thereof, and methods for inhibition of HIV-integrase are disclosed.
三环化合物，其受保护的中间体，以及用于抑制HIV整合酶的方法被披露。
PYRIMIDINYL AND 1,3,5-TRIAZINYL BENZIMIDAZOLES AND THEIR USE IN CANCER THERAPY
申请人：Rewcastle Gordon William
公开号：US20110009405A1
公开（公告）日：2011-01-13
Provided herein are pyrimidinyl and 1,3,5-triazinyl benzimidazoles of Formula I, and their pharmaceutical compositions, preparation, and use as agents or drugs for cancer therapy, either alone or in combination with radiation and/or other anticancer drugs.
![NSC 317629; 1-[4-[4-[[2-(2,4-二氯苯基)-2-(1H-咪唑-1-甲基)-1,3-二氧杂环戊-4-基]甲氧基]苯基]-1-哌嗪基]乙酮化学式](data:image/svg+xml;base64,<?xml version="1.0" encoding="UTF-8"?>
<svg xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink" width="300" height="300" viewBox="0 0 300 300">
<defs>
<g>
<g id="glyph-0-0">
<path d="M 0.515625 1.8125 L 0.515625 -7.25 L 5.65625 -7.25 L 5.65625 1.8125 Z M 1.09375 1.25 L 5.078125 1.25 L 5.078125 -6.671875 L 1.09375 -6.671875 Z M 1.09375 1.25 "/>
</g>
<g id="glyph-0-1">
<path d="M 4.046875 -6.8125 C 3.316406 -6.8125 2.734375 -6.535156 2.296875 -5.984375 C 1.859375 -5.429688 1.640625 -4.679688 1.640625 -3.734375 C 1.640625 -2.796875 1.859375 -2.050781 2.296875 -1.5 C 2.734375 -0.945312 3.316406 -0.671875 4.046875 -0.671875 C 4.785156 -0.671875 5.367188 -0.945312 5.796875 -1.5 C 6.234375 -2.050781 6.453125 -2.796875 6.453125 -3.734375 C 6.453125 -4.679688 6.234375 -5.429688 5.796875 -5.984375 C 5.367188 -6.535156 4.785156 -6.8125 4.046875 -6.8125 Z M 4.046875 -7.625 C 5.097656 -7.625 5.9375 -7.269531 6.5625 -6.5625 C 7.195312 -5.863281 7.515625 -4.921875 7.515625 -3.734375 C 7.515625 -2.554688 7.195312 -1.613281 6.5625 -0.90625 C 5.9375 -0.207031 5.097656 0.140625 4.046875 0.140625 C 2.992188 0.140625 2.148438 -0.207031 1.515625 -0.90625 C 0.890625 -1.613281 0.578125 -2.554688 0.578125 -3.734375 C 0.578125 -4.921875 0.890625 -5.863281 1.515625 -6.5625 C 2.148438 -7.269531 2.992188 -7.625 4.046875 -7.625 Z M 4.046875 -7.625 "/>
</g>
<g id="glyph-0-2">
<path d="M 1.015625 -7.5 L 2.375 -7.5 L 5.703125 -1.21875 L 5.703125 -7.5 L 6.6875 -7.5 L 6.6875 0 L 5.3125 0 L 2 -6.265625 L 2 0 L 1.015625 0 Z M 1.015625 -7.5 "/>
</g>
<g id="glyph-0-3">
<path d="M 6.625 -6.921875 L 6.625 -5.84375 C 6.28125 -6.164062 5.914062 -6.40625 5.53125 -6.5625 C 5.144531 -6.71875 4.734375 -6.796875 4.296875 -6.796875 C 3.441406 -6.796875 2.785156 -6.53125 2.328125 -6 C 1.867188 -5.476562 1.640625 -4.722656 1.640625 -3.734375 C 1.640625 -2.753906 1.867188 -2 2.328125 -1.46875 C 2.785156 -0.945312 3.441406 -0.6875 4.296875 -0.6875 C 4.734375 -0.6875 5.144531 -0.765625 5.53125 -0.921875 C 5.914062 -1.078125 6.28125 -1.316406 6.625 -1.640625 L 6.625 -0.578125 C 6.269531 -0.335938 5.894531 -0.15625 5.5 -0.03125 C 5.101562 0.0820312 4.679688 0.140625 4.234375 0.140625 C 3.097656 0.140625 2.203125 -0.203125 1.546875 -0.890625 C 0.898438 -1.585938 0.578125 -2.535156 0.578125 -3.734375 C 0.578125 -4.941406 0.898438 -5.890625 1.546875 -6.578125 C 2.203125 -7.273438 3.097656 -7.625 4.234375 -7.625 C 4.679688 -7.625 5.101562 -7.566406 5.5 -7.453125 C 5.894531 -7.335938 6.269531 -7.160156 6.625 -6.921875 Z M 6.625 -6.921875 "/>
</g>
<g id="glyph-0-4">
<path d="M 0.96875 -7.8125 L 1.890625 -7.8125 L 1.890625 0 L 0.96875 0 Z M 0.96875 -7.8125 "/>
</g>
<g id="glyph-0-5">
<path d="M 1.015625 -7.5 L 2.015625 -7.5 L 2.015625 -4.421875 L 5.703125 -4.421875 L 5.703125 -7.5 L 6.71875 -7.5 L 6.71875 0 L 5.703125 0 L 5.703125 -3.5625 L 2.015625 -3.5625 L 2.015625 0 L 1.015625 0 Z M 1.015625 -7.5 "/>
</g>
<g id="glyph-1-0">
<path d="M 0.34375 1.21875 L 0.34375 -4.84375 L 3.765625 -4.84375 L 3.765625 1.21875 Z M 0.734375 0.828125 L 3.390625 0.828125 L 3.390625 -4.453125 L 0.734375 -4.453125 Z M 0.734375 0.828125 "/>
</g>
<g id="glyph-1-1">
<path d="M 2.78125 -2.703125 C 3.101562 -2.628906 3.351562 -2.484375 3.53125 -2.265625 C 3.71875 -2.046875 3.8125 -1.773438 3.8125 -1.453125 C 3.8125 -0.960938 3.640625 -0.582031 3.296875 -0.3125 C 2.960938 -0.0390625 2.484375 0.09375 1.859375 0.09375 C 1.648438 0.09375 1.429688 0.0703125 1.203125 0.03125 C 0.984375 -0.0078125 0.753906 -0.0703125 0.515625 -0.15625 L 0.515625 -0.796875 C 0.703125 -0.691406 0.90625 -0.609375 1.125 -0.546875 C 1.351562 -0.492188 1.59375 -0.46875 1.84375 -0.46875 C 2.257812 -0.46875 2.578125 -0.550781 2.796875 -0.71875 C 3.023438 -0.882812 3.140625 -1.128906 3.140625 -1.453125 C 3.140625 -1.742188 3.035156 -1.972656 2.828125 -2.140625 C 2.617188 -2.304688 2.332031 -2.390625 1.96875 -2.390625 L 1.390625 -2.390625 L 1.390625 -2.953125 L 2 -2.953125 C 2.332031 -2.953125 2.585938 -3.015625 2.765625 -3.140625 C 2.941406 -3.273438 3.03125 -3.46875 3.03125 -3.71875 C 3.03125 -3.976562 2.9375 -4.175781 2.75 -4.3125 C 2.570312 -4.445312 2.3125 -4.515625 1.96875 -4.515625 C 1.78125 -4.515625 1.582031 -4.492188 1.375 -4.453125 C 1.164062 -4.421875 0.929688 -4.363281 0.671875 -4.28125 L 0.671875 -4.875 C 0.929688 -4.945312 1.171875 -5 1.390625 -5.03125 C 1.617188 -5.070312 1.832031 -5.09375 2.03125 -5.09375 C 2.539062 -5.09375 2.945312 -4.972656 3.25 -4.734375 C 3.550781 -4.503906 3.703125 -4.191406 3.703125 -3.796875 C 3.703125 -3.515625 3.617188 -3.28125 3.453125 -3.09375 C 3.296875 -2.90625 3.070312 -2.773438 2.78125 -2.703125 Z M 2.78125 -2.703125 "/>
</g>
</g>
</defs>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 8.062511 2.57087 L 8.836344 1.921629 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 8.062511 2.57087 L 7.385009 2.791488 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 8.062511 2.57087 L 7.651968 1.646161 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 8.062511 2.57087 L 8.457404 3.114057 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 8.82905 1.927859 L 8.655535 0.942829 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 8.976433 1.804179 L 8.836344 1.008619 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 8.819934 1.924516 L 9.777918 2.273067 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 7.112276 3.141711 L 7.11182 3.880445 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 7.668378 1.656037 L 6.885581 1.711343 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 8.457404 3.646153 L 8.05537 4.199064 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 8.648241 0.948906 L 9.428911 0.294803 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 8.664651 0.94602 L 8.021183 0.711879 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 9.761509 2.275954 L 10.542027 1.620635 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 9.728082 2.086484 L 10.361218 1.554845 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 7.11182 3.880445 L 8.074059 4.192986 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 7.11182 3.880445 L 6.293165 4.474228 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 6.494942 1.988939 L 6.122232 2.585457 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 6.459236 1.489358 L 6.008884 0.951641 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 9.412502 0.29769 L 10.360762 0.64305 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 9.445777 0.48716 L 10.21338 0.76673 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 10.536405 1.636285 L 10.358939 0.633478 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 6.299394 4.456147 L 6.496309 5.142766 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 6.140465 2.578012 L 5.412366 2.396443 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 6.063279 2.387022 L 5.452782 2.234626 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 6.027877 0.956352 L 5.077034 1.340457 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 5.977889 1.156305 L 5.251765 1.449702 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 10.353317 0.64928 L 10.855632 0.227493 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 6.315196 5.620163 L 5.760766 6.022957 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 5.140089 2.070379 L 5.087366 1.323895 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 5.768515 6.017183 L 5.874265 7.020749 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 5.612928 6.130378 L 5.69847 6.942652 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 5.777327 6.021133 L 4.846388 5.606336 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 5.881103 7.005555 L 5.056978 7.605112 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 4.86295 5.604665 L 4.038825 6.202854 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 4.883006 5.795958 L 4.21462 6.281255 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 5.073539 7.603441 L 4.150197 7.192442 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 5.053331 7.411996 L 4.305936 7.079398 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 4.045662 6.18766 L 4.151109 7.202014 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 4.157946 7.18682 L 3.585891 7.602529 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 3.368616 8.045739 L 3.444282 8.786145 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 3.086462 7.667408 L 2.419444 7.372339 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 3.450968 8.770951 L 2.626235 9.372331 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 2.436006 7.370516 L 1.610665 7.973112 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 2.642948 9.370508 L 1.977753 9.073616 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 1.617351 7.957918 L 1.694536 8.693765 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 1.477869 9.136975 L 0.90551 9.552381 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 0.991204 9.490237 L 0.315981 9.189243 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 0.923287 9.642329 L 0.248064 9.341487 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<path fill="none" stroke-width="0.0333333" stroke-linecap="butt" stroke-linejoin="miter" stroke="rgb(0%, 0%, 0%)" stroke-opacity="1" stroke-miterlimit="10" d="M 0.912347 9.537186 L 0.989077 10.269995 " transform="matrix(25.709091, 0, 0, 25.709091, 6.583449, 14.338853)"/>
<g fill="rgb(100%, 5.1%, 5.1%)" fill-opacity="1">
<use xlink:href="#glyph-0-1" x="185.386719" y="92.132812"/>
</g>
<g fill="rgb(100%, 5.1%, 5.1%)" fill-opacity="1">
<use xlink:href="#glyph-0-1" x="224.9375" y="104.980469"/>
</g>
<g fill="rgb(19%, 31%, 97.000003%)" fill-opacity="1">
<use xlink:href="#glyph-0-2" x="173.921875" y="62.492187"/>
</g>
<g fill="rgb(9.977717%, 78.158784%, 9.977717%)" fill-opacity="1">
<use xlink:href="#glyph-0-3" x="200.121094" y="33.617188"/>
<use xlink:href="#glyph-0-4" x="207.301563" y="33.617188"/>
</g>
<g fill="rgb(100%, 5.1%, 5.1%)" fill-opacity="1">
<use xlink:href="#glyph-0-1" x="171.660156" y="157.65625"/>
</g>
<g fill="rgb(19%, 31%, 97.000003%)" fill-opacity="1">
<use xlink:href="#glyph-0-2" x="135.359375" y="78.066406"/>
</g>
<g fill="rgb(9.977717%, 78.158784%, 9.977717%)" fill-opacity="1">
<use xlink:href="#glyph-0-3" x="287.808594" y="18.171875"/>
<use xlink:href="#glyph-0-4" x="294.989063" y="18.171875"/>
</g>
<g fill="rgb(19%, 31%, 97.000003%)" fill-opacity="1">
<use xlink:href="#glyph-0-2" x="88.644531" y="218.105469"/>
</g>
<g fill="rgb(19%, 31%, 97.000003%)" fill-opacity="1">
<use xlink:href="#glyph-0-2" x="47.019531" y="248.429687"/>
</g>
<g fill="rgb(100%, 5.1%, 5.1%)" fill-opacity="1">
<use xlink:href="#glyph-0-1" x="2.535156" y="253.054688"/>
</g>
<g fill="rgb(0%, 0%, 0%)" fill-opacity="1">
<use xlink:href="#glyph-0-3" x="29.140625" y="289.089844"/>
</g>
<g fill="rgb(0%, 0%, 0%)" fill-opacity="1">
<use xlink:href="#glyph-0-5" x="35.613281" y="288.953125"/>
</g>
<g fill="rgb(0%, 0%, 0%)" fill-opacity="1">
<use xlink:href="#glyph-1-1" x="42.671875" y="289.542969"/>
</g>
</svg>
)
